Chronic Arsenic Poisoning From Burning High-Arsenic-Containing Coal In Guizhou, China

Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED90 less than or equal to 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED90 values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day.     

Precise intraoperative location of gastrointestinal bleeding with a hand-held counter. Work in progress

The nuclear medicine bleeding scan is frequently insufficient to locate sites of bleeding precisely, in spite of its great sensitivity. A small, hand-held Geiger-Müller counter, placed directly on exposed intestine in the operating room, enables precise location of the probable bleeding site. In three patients, the technique allowed a minimal amount of intestine to be resected, distinguished between large- and small-intestinal hemorrhage, and eliminated other foci as sites of bleeding.     

A brief conceptual tutorial of multilevel analysis in social epidemiology: using measures of clustering in multilevel logistic regression to investigate contextual phenomena

STUDY OBJECTIVE: In social epidemiology, it is easy to compute and interpret measures of variation in multilevel linear regression, but technical difficulties exist in the case of logistic regression. The aim of this study was to present measures of variation appropriate for the logistic case in a didactic rather than a mathematical way. Design and PARTICIPANTS: Data were used from the health survey conducted in 2000 in the county of Scania, Sweden, that comprised 10 723 persons aged 18-80 years living in 60 areas. Conducting multilevel logistic regression different techniques were applied to investigate whether the individual propensity to consult private physicians was statistically dependent on the area of residence (that is, intraclass correlation (ICC), median odds ratio (MOR)), the 80% interval odds ratio (IOR-80), and the sorting out index). RESULTS: The MOR provided more interpretable information than the ICC on the relevance of the residential area for understanding the individual propensity of consulting private physicians. The MOR showed that the unexplained heterogeneity between areas was of greater relevance than the individual variables considered in the analysis (age, sex, and education) for understanding the individual propensity of visiting private physicians. Residing in a high education area increased the probability of visiting a private physician. However, the IOR showed that the unexplained variability between areas did not allow to clearly distinguishing low from high propensity areas with the area educational level. The sorting out index was equal to 82%. CONCLUSION: Measures of variation in logistic regression should be promoted in social epidemiological and public health research as efficient means of quantifying the importance of the context of residence for understanding disparities in health and health related behaviour.     

Clinical and familial study of arrhythmogenic right ventricular cardiomyopathy

Objective　To explore the characteristics of arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods　Seven patients with arrhythmogenic right ventricular cardiomyopathy and 34 members of three families were studied. All patients and family members underwent history collection, clinical examination, electrocardiogram (ECG), two-dimensional echocardiography (2-DE) and a signal averaging electrocardiogram. Programmed ventricular stimulation was performed in five patients. Results　All patients and family members had normal morphologic characteristics and normal function of the left ventricular by 2-DE. Fourteen persons had abnormal findings indicating ARVC. Five had enlargement of the right ventricular with diffused hypocontractility, eight had thin and systolic bulging in the focal anterior wall with hypokinesia and one had bulging of the inferior wall. Twenty-five persons (seven patients and 18 family members) had abnormal findings in ECG. Positive ventricular late potential was recorded in 13 persons (six patients). Two to three monomorphic ventricular tachycardia (VT) with left bundle branch block (LBBB) configurations were induced in five patients. Ventricular fibrillation was induced in two patients during the electrophysiologic study (EPS). Five patients had very high pacing threshold and/or ineffective pacing in one or many regions of the right ventricle. Two members of one family died suddenly. One member was a dwarf with ARVC. Spontaneous VT with a left bundle branch block (LBBB) configuration was recorded in five patients, polymorphic VT with extremely short coupling interval in one, and premature ventricular complexes with LBBB configuration in 12 (six patients). Conclusion　Our familial study strongly suggests that ARVC may be a hereditary disease and it is helpful in the diagnosis and detection of ARVC. The most common manifestations were abnormal structure and function of the right ventricle and abnormal ECG of repolarization and ventricular arrhythmia which originates from the right ventricle.     

Why socially deprived populations have a faster resting heart rate: impact of behaviour, life course anthropometry, and biology--the RECORD Cohort Study

Although studies have shown that resting heart rate (RHR) is predictive of cardiovascular morbidity/mortality, few studies focused on the epidemiology and social aetiology of RHR. Using the RECORD Cohort Study (7158 participants, 2007–2008, Paris region, France), we investigated individual/neighbourhood socioeconomic variables associated with resting heart rate, and assessed which of a number of psychological factors (depression and stress), behaviour (sport-related energy expenditure, medication use, and alcohol, coffee, and tobacco consumption), life course anthropometric factors (body mass index, waist circumference, and leg length as a marker of childhood environmental exposures), and biologic factors (alkaline phosphatase and gamma-glutamyltransferase) contributed to the socioeconomic disadvantage–RHR relationship. Combining individual/neighbourhood socioeconomic factors in a socioeconomic score, RHR increased with socioeconomic disadvantage: +0.9 [95% credible interval (CrI): +0.2, +1.6], +1.8 (95% CrI: +1.0, +2.5), and +3.6 (95% CrI: +2.9, +4.4) bpm for the 3 categories reflecting increasing disadvantage, compared with the lowest disadvantage category. Twenty-one percent of the socioeconomic disadvantage–RHR relationship was explained by sport practise variables, 9% by waist circumference, 7% by gamma-glutamyltransferase, 5% by alkaline phosphatase, and 3% by leg length. Future research should further clarify the mechanisms through which socioeconomic disadvantage influences resting heart rate, as a pathway to social disparities in cardiovascular morbidity/mortality.     

基因芯片技术在脑损伤研究中的应用

基因芯片技术是最近发展起来的新兴分子生物学技术,它的并行处理特点使大规模研究脑损伤后的基因改变成为切实可能。本文综述了新近用基因芯片技术在脑损伤后基因表达时序性改变及基因表达谱分析等研究中的应用。