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Background: Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. Methods: In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. Results: Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of ‘major’ incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). Conclusions: The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer. [ABSTRACT FROM AUTHOR]

Background: A previously conducted study of prenatal lead exposure and schizophrenia using delta-aminolevulinic acid, a biologic marker of Pb exposure, in archived maternal serum samples collected from subjects enrolled in the Childhood Health and Development Study (1959-1966) based in Oakland, California, suggested a possible association between prenatal Pb exposure and the development of schizophrenia in later life.Objectives: In the present study we extend these findings using samples collected from the New England cohort of the National Collaborative Perinatal Project (1959-1966) . Using similar methods, in this study we found results that suggest a comparable association in this cohort.Methods: We pooled matched sets of cases and controls from both the California and New England sites using a multilevel random-intercept logistic regression model, accounting for matching and site structure as well as adjusting for maternal age at delivery and maternal education.Results: The estimated odds ratio for schizophrenia associated with exposure corresponding to 15 µg/dL of blood Pb was 1.92 (95% confidence interval, 1.05-3.87 ; p = 0.03) .Conclusion: Although several limitations constrain generalizability, these results are consistent with previous findings and provide further evidence for the role of early environmental exposures in the development of adult-onset psychiatric disorders. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (p≤0.034), and this association was strongest among the individuals with arsenic-induced skin lesions (p ≤ 0.002). When the study subjects were stratified in tertiles of serum EGFR ECD levels, the risk of skin lesions increased progressively for each increase in all three arsenic measures (also stratified in tertiles) and this increasing risk became more pronounced among subjects within the highest tertile of EGFR ECD levels. These results suggest that serum EGFR ECD levels may be a potential biomarker of effect of arsenic exposure and may indicate those exposed individuals at greatest risk for the development of arsenic-induced skin lesions. [ABSTRACT FROM AUTHOR]

Schizophrenia is a severe mental disorder of unknown etiology. Recent reports suggest that a number of environmental factors during prenatal development may be associated with schizophrenia. We tested the hypothesis that environmental lead exposure may be associated with schizophrenia using archived serum samples from a cohort of live births enrolled between 1959 and 1966 in Oakland, California. Cases of schizophrenia spectrum disorder were identified and matched to controls. A biologic marker of lead exposure, delta-aminolevulinic acid (delta -ALA), was determined in second-trimester serum samples of 44 cases and 75 controls. delta -ALA was stratified into high and low categories, yielding 66 subjects in the high category, corresponding to a blood lead level (BPb) >/= 15 microg/dL, and 53 in the low category, corresponding to BPb < 15 microg/dL. Using logistic regression, the odds ratio (OR) for schizophrenia associated with higher delta -ALA was 1.83 [95% confidence interval (CI), 0.87-3.87; p = 0.1]. Adjusting for covariates gave an OR of 2.43 (95% CI, 0.99-5.96; p = 0.051). This finding suggests that the effects of prenatal exposure to lead and/or elevated delta -ALA may extend into later life and must be further investigated as risk factors for adult psychiatric diseases. [ABSTRACT FROM AUTHOR]

There is widespread concern regarding the safety of silver-mercury amalgam dental restorations, yet little evidence to support their harm or safety. We examined whether mercury dental amalgams are adversely associated with cognitive functioning in a cross-sectional sample of healthy working adults. We studied 550 adults, 30-49 years of age, who were not occupationally exposed to mercury. Participants were representative of employees at a major urban medical center. Each participant underwent a neuropsychologic test battery, a structured questionnaire, a modified dental examination, and collection of blood and urine samples. Mercury exposure was assessed using a) urinary mercury concentration (UHg); b) the total number of amalgam surfaces; and c) the number of occlusal amalgam surfaces. Linear regression analysis was used to estimate associations between each marker of mercury exposure and each neuropsychologic test, adjusting for potential confounding variables. Exposure levels were relatively low. The mean UHg was 1.7 microg/g creatinine (range, 0.09-17.8); the mean total number of amalgam surfaces was 10.6 (range, 0-46) and the mean number of occlusal amalgam surfaces was 6.1 (range, 0-19). No measure of exposure was significantly associated with the scores on any neuropsychologic test in analyses that adjusted for the sampling design and other covariates. In a sample of healthy working adults, mercury exposure derived from dental amalgam restorations was not associated with any detectable deficits in cognitive or fine motor functioning. [ABSTRACT FROM AUTHOR]

Arsenic concentrations measured by graphite furnace atomic absorption range from < 5 to 900 μg/L in groundwater pumped from 6000 wells within a 25 km2 area of Bangladesh. The proportion of wells that exceed the Bangladesh standard for drinking water of 50 μg/L arsenic increases with depth from 25% between 8 and 10 m to 75% between 15 and 30 m, then declines gradually to less than 10% at 90 m. Some villages within the study area do not have a single well that meets the standard, while others have wells that are nearly all acceptable. In contrast to the distribution of arsenic in the 8-30 m depth range which does not follow any obvious geological feature, the arsenic content of groundwater associated with relatively oxic Pleistocene sand deposits appears to be consistently low. The depth of drilling necessary to reach these low-As aquifers ranges from 30 to 120 m depth within the study area. [ABSTRACT FROM AUTHOR]

A polyester mesh 'jacket' fitted over the ventricles may succeed where other therapies have failed -- by halting, or even reserving, cardiac damage due to heart failure. [ABSTRACT FROM AUTHOR]

In the chronically-instrumented animal and the isolated blood perfused heart, atrial re-entry via a fixed path around an anatomic obstacle has been described and is terminated by the class III antiarrhythmic agent d-sotalol. The precise mechanism by which d-sotalol terminates this arrhythmia is not known.In the present study, right atrial (RA) activation sequences in the isolated, coronary artery perfused canine heart (n = 5) during episodes of sustained flutter and drug administration were determined. A fixed array of bipolar electrodes was used to record endocardial electrograms from 96 sites on the RA simultaneously. Maps of all control flutters showed that the rhythm was due to persistent circus movement of the impulse around the tricuspid valve ring. d-Sotalol was effective in terminating atrial re-entry in this model. In all episodes, block of the excitatory impulse in a specific region of the re-entrant circuit accompanied these terminatons. However, the events preceding the occurrence of block of the impulse were not similar. Two different modes of termination are described.The class III antiarrhythmic agent d-sotalol can terminate atrial re-entry in several ways. In one mode, complete conduction block of the re-entering impulse within the fixed path occurs to terminate the rhythm. In the other mode, interruption of the original re-entrant circuit occurs when there is failure of a lateral boundary. In both modes cycle length (CL) oscillations are observed. [ABSTRACT FROM PUBLISHER]

OBJECTIVES: Interpreting associations between lead exposure and child behavior problems is difficult because studies have not controlled for sociodemographic confounders or have used shed teeth to mark exposure. This study explored associations between blood lead and preschool behavior. METHODS: Children from a smelter town and a non-lead-exposed town in Yugoslavia were followed up prospectively from pregnancy through age 3. The Child Behavior Checklist was used to assess behavior problems in 379 3-year-olds, controlling for sociodemographic factors and difficult infant temperament. RESULTS: Multiple regression revealed the expected significant associations between checklist subscales and sociodemographic factors, which explained 7% to 18% of the variance on the subscales. Concurrent blood lead explained a significant 1% to 4% of the variance on the Destructive and Withdrawn subscales. Earlier difficult temperament explained an additional 2% to 5% of the checklist variance. Scores on the Destructive subscale were consistently associated with blood lead. As blood lead increased from 10 to 20 micrograms/dL, subscale scores increased by approximately 0.5 points. CONCLUSIONS: Lead/behavior associations are significant but small compared with the effects of social factors. [ABSTRACT FROM AUTHOR]

A response by J. N. Graziano to a letter to the editor about his article "The Influence of a Restrictive Atrial Septal Defect on Pulmonary Vascular Morphology in Patients With Hypoplastic Left Heart Syndrome," in a previous issue of the journal "Pediatric Cardiology" is presented.