Mortality among children residing near the American Smelting and Refining Company (ASARCO) copper smelter in Ruston, Washington

A retrospective cohort study was undertaken to determine whether childhood exposure to ambient arsenic was associated with increased mortality rates. Cohort members comprised children who had lived within 4.0 km (2.5 mi) of the American Smelting and Refining Company (ASARCO) copper smelter and arsenic refinery in Ruston, Washington, for at least 2 yr during the time period from 1907 to 1932. The cohort included 1,827 boys and 1,305 girls identified from school census records. Exposure intensity was computed as the total number of years a child had lived at a residence less than 1.6 km (1.0 mi) from the smelter stack during the study period. In only one exposure intensity group (i.e., residence > or = 10.0 yr less than 1.6 km [1.0 mi] from the smelter) for boys were Cox proportional hazards ratios significantly higher than 1.00: for all causes of death (1.52), ischemic heart disease (1.77), and external causes (1.93). For girls, hazard ratios were not elevated significantly for any cause of death in any exposure intensity group.     

Effect of over-the-counter cimetidine on phenytoin concentrations in patients with seizures.

OBJECTIVE: To determine the effects of the maximum recommended over-the-counter (OTC) cimetidine dosage on phenytoin concentrations in ambulatory seizure patients on long-term phenytoin therapy. METHODS: Adults with seizure disorders requiring phenytoin therapy were recruited. Trough total phenytoin concentrations were measured initially and once weekly for six weeks. All assays were performed using Biotrack patient-side cartridges. After a two-week baseline period, patients took cimetidine 200 mg twice daily for two weeks. Toxicity was monitored via weekly neurologic examinations and midweek telephone surveys. Patients were asked to return to clinic weekly during a two-week cimetidine washout period. RESULTS: Nine patients entered and completed the study. All but two patients took other anticonvulsants known to interact with phenytoin (carbamazepine, n = 5; phenobarbital, n = 2). No adverse effects or changes in seizure frequency were reported. Paired Student's t-tests revealed no significant difference between serum phenytoin concentrations before (12.3+/-3.2 mg/L [mean +/- SD]) and after (12.8+/-4.0 mg/L) two weeks on the OTC cimetidine regimen. No differences were noted in estimated pharmacokinetic parameters (maximum metabolic rate, Michaelis-Menten constant) for the same time periods (paired Student's t-test, p > 0.05). The Biotrack assay had an r2 = 0.7311 (p < 0.001, two-sided) when compared with TDx. CONCLUSIONS: It is possible that the lack of change in phenytoin concentrations was a result of the low daily dosage of cimetidine used or other factors related to the "real world" setting of the study. However, the potential for a serious drug interaction occurring in patients taking long-term oral phenytoin and OTC cimetidine appears to be small.     

A systematic review of the epidemiology and interaction of herpes simplex virus types 1 and 2

OBJECTIVES: To explore epidemiological evidence about the interaction of herpes simplex virus (HSV) 1 and HSV-2 infections. METHODS: A systematic review was undertaken of published epidemiological studies describing the pattern of HSV-1 or HSV-2 by age, and the coincidence of the two viral infections. RESULTS: In cross sectional studies the unadjusted odds of HSV-2 are greater in those with HSV-1 infection in study populations categorised as "low risk" (p = 0.06) and across European populations (p = 0.001). This was not evident in "high risk" populations or in the United States. This increased risk of HSV-2 in those with HSV-1 infection does not agree with the results of prospective studies where there is a non-significant trend towards a lower risk of HSV-2 infection associated with previous HSV-1 infection. CONCLUSIONS: "Low risk" and European populations have a relatively low HSV-2 seroprevalence and infection is more concentrated in those with characteristics putting them at high risk for both HSV-1 and HSV-2. This confounding could mask any protective effect of HSV-1, which is hinted at, but not demonstrated, in prospective and adjusted studies.     

The epidemiological impact of antiretroviral use predicted by mathematical models: a review

This review summarises theoretical studies attempting to assess the population impact of antiretroviral therapy (ART) use on mortality and HIV incidence. We describe the key parameters that determine the impact of therapy, and argue that mathematical models of disease transmission are the natural framework within which to explore the interaction between antiviral use and the dynamics of an HIV epidemic. Our review focuses on the potential effects of ART in resource-poor settings. We discuss choice of model type and structure, the potential for risk behaviour change following widespread introduction of ART, the importance of the stage of HIV infection at which treatment is initiated, and the potential for spread of drug resistance. These issues are illustrated with results from models of HIV transmission. We demonstrate that HIV transmission models predicting the impact of ART use should incorporate a realistic progression through stages of HIV infection in order to capture the effect of the timing of treatment initiation on disease spread. The realism of existing models falls short of properly reproducing patterns of diagnosis timing, incorporating heterogeneity in sexual behaviour, and describing the evolution and transmission of drug resistance. The uncertainty surrounding certain effects of ART, such as changes in sexual behaviour and transmission of ART-resistant HIV strains, demands exploration of best and worst case scenarios in modelling, but this must be complemented by surveillance and behavioural surveys to quantify such effects in settings where ART is implemented.     

马兜铃酸的倍半萜的酯类化合物VI.绵毛马兜铃中马兜铃酸萜酯I的结构鉴定

从绵毛马兜铃(Aristolocha mannisima Hance)中分得一个马兜铃酸倍半萜的酯类化合物,经红外、紫外、高分辩质谱和多种一维和二维核磁共振谱鉴定,确定了其骨架结构及顺反构型,命名为马兜铃酸萜酯I。     

Clinical multimorbidity and physical function in older adults: a record and health status linkage study in general practice

BACKGROUND: Multiple chronic conditions occurring in the same individual are associated with adverse health outcomes. In family practice, individuals are seen who, over time, may experience many different symptoms, illnesses and chronic diseases. Measures for defining multimorbidity, which incorporate the diverse range of health problems seen in population-based family practice, remain to be developed. We have investigated whether routinely collected consultation data could be used as the basis for a simple classification of multimorbidity that reflects an individual's overall health status. METHODS: Morbidity consultation data for 9,439 English patients aged 50 years and over in an 18-month time period were linked to their self-reported physical health status measured by Short-Form 12 at the end point. Associations between physical function and all-cause multimorbidity counts were estimated relative to single morbidity only, and between physical function and morbidity severity (185 morbidities categorized on four ordinal scales of severity) relative to persons who had not consulted about any of the 185. RESULTS: In the 18-month period, 19% had consulted for a single morbidity and 23% for six or more (a high multimorbidity count). An estimated 24% of poor physical function in the family practice consulting population may be attributable to high multimorbidity. There was an increasing strength of association between poor physical function and increasing severity of multimorbidity on all four severity scales. Estimated associations (adjusted odds ratios) of the most severe morbidity categories with poor physical function were, for each of the four scales, respectively, 5.6 for chronicity [95% confidence interval (CI) 4.4-7.1], 7.0 for time course (4.5-10.6) and 3.6 for health care use (2.0-6.6) and for patient impact (6.7; 5.2-8.8). CONCLUSIONS: Multimorbidity defined by using routinely collected family practice consultation data and classified by count and by severity was associated with poorer physical function. This approach offers the potential for systematic use of routine records to classify multimorbidity and to identify groups with high likelihood of poor physical status for needs assessment and targeted intervention.     

Elevated retinal zeaxanthin and prevention of light-induced photoreceptor cell death in quail

PURPOSE: Inferential evidence indicates that macular pigments (lutein and zeaxanthin) protect photoreceptors and/or retard age-related macular degeneration. These experiments tested the hypothesis that retinal zeaxanthin prevents light-induced photoreceptor cell death. METHODS: Retinal damage was assessed in quail fed a carotenoid-deficient (C-) diet for 6 months. Groups of 16 birds (8 male, 8 female) were fed a C- diet supplemented with 35 mg 3R,3'R-zeaxanthin for 1, 3, or 7 days; one group was continued on C- diets. Half of each group was exposed to intermittent 3200-lux white light (10 1-hour intervals separated by 2 hours in dark). After 14 additional hours in the dark, one retina of each quail was collected for HPLC analysis, and the contralateral retina was embedded in paraffin for counts of apoptotic nuclei. RESULTS: After 7 days' supplementation, concentrations of zeaxanthin in serum, liver, and fat had increased by factors of 50.8, 43.2, and 6.5, respectively (all P < 0.001). In contrast, retinal zeaxanthin fluctuated significantly upward on day 3, but there was no net change on day 7. The number of apoptotic rods and cones in light-damaged eyes correlated significantly and inversely with zeaxanthin concentration in the contralateral retina (r = -0.61; P < 0.0001 and r = -0.54; P < 0.002), but not with serum zeaxanthin. Similar correlations were observed with retinal lutein, which correlated strongly with retinal zeaxanthin (r = 0.95; P < 0.0001). CONCLUSIONS: Retinal zeaxanthin dose dependently reduced light-induced photoreceptor apoptosis; elevated serum levels did not. These data provide the first experimental evidence that xanthophyll carotenoids protect photoreceptors in vivo.