Blood-brain barrier breakdown by cold injury. Polyamine signals mediate acute stimulation of endocytosis, vesicular transport, and microvillus formation in rat cerebral capillaries

Polyamines have been previously implicated in the mediation of blood-brain barrier breakdown induced by cryogenic injury (H Koenig, AD Goldstone, CY Lu, Biochem Biophys Res Commun 116:1039, 1983). We studied acute (less than 5 minute) changes in capillary ultrastructure, microvascular permeability, and the levels of polyamines and their rate regulating synthetic enzyme ornithine decarboxylase (ODC) in rat cerebral cortex after focal cold injury. Microvascular permeability was measured by relative transport of intravenously administered fluorescein. Capillary ultrastructure was studied by quantitative stereology and morphometry after intravenous administration of horseradish peroxidase. Focal cold injury induced a 2.5-, 3.8-, 1.7-, and 1.4-fold increase in the levels of ODC, putrescine, spermidine and spermine, and a 46-fold increase in fluorescein uptake in perilesional cortex. Few capillaries in control cortex contained endocytic pits or horseradish peroxidase-positive vesicles, whereas most capillaries near lesions showed these structures. Cryoinjury induced a 5-fold increase in the relative volume of microvilli and horseradish peroxidase vesicles, a 2.3-fold increase in area of luminal endocytic pits, and a 6.3-fold increase in area of abluminal exocytic pits. The ODC inhibitor alpha-difluoromethylornithine blocked the cryoinjury-induced changes in ODC, polyamines, fluorescein uptake, and capillary ultrastructure. Putrescine negated the effect of alpha-difluoromethylornithine or capillary ultrastructure, and was previously shown to nullify the alpha-difluoromethylornithine effects on polyamines and fluorescein permeability (cited above). These data link rapid changes in ODC and polyamines to blood-brain barrier breakdown, and suggest that the abnormal permeability is associated with an acute, polyamine-mediated stimulation of microvillus formation, endocytosis, and vesicular transport in capillary endothelium.     

Psychotropic drug utilization patterns in a metropolitan population

Summary Psychotropic drug intake by a random sample of citizens of the city of Munich aged 30–69 years has been assessed. A 1-week prevalence of 9.3% for all psychotropic drug users was found, benzodiazepines accounting for approximately two-thirds (6.6%) of the users. Two-thirds of drug users were women. Drug use in both sexes increased with age. The doses of benzodiazepines prescribed in most cases were less than 10 mg diazepam equivalent per day. Intake of benzodiazepines in combination with analgesics or alcohol (40 g/day) did not appear to represent a major problem. Multiple logistic regression analysis showed that the number of chronic diseases was the strongest predictor of benzodiazepine intake in men, whereas stress and age determined intake in women. Long-term use seemed to be relatively rare at 11% of all benzodiazepine users, so it was not considered to be a severe public health problem.     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

胰腺切除术后出血的诊断与治疗：669例连续胰腺切除术分析

目的：分析胰腺切除术后出血（postpancreatectomy hemorrhage，PPH）的临床病程及预后。背景：PPH是最致命的胰腺术后并发症，但目前仍缺少其标准治疗规程。方法：1992年至2006年，对1524例施行胰腺手术的患者进行了前瞻性研究。根据以下指标进行PPH危险分级：PPH严重程度（轻度，即血红蛋白浓度下降〈3g／dL；重度，即血红蛋白浓度下降〉3g／dL），PPH出现时间（早期，即术后1～5天；晚期，术后第6天），合并胰瘘，肠道内或肠道外出血表现以及存在“复杂的”血管病理变化（腐蚀、假性动脉瘤）。     

病灶清除内固定植骨治疗胸椎结核

目的;探讨手术治疗胸椎结核的更好方法。方法;自１９９０年以来,对２１例胸椎结核导致椎柱不稳的患者,应用病灶清除,哈氏棒内固定,椎间及椎板植骨的手术方法。本组平均３３．２岁。胸７椎体６例,胸８椎体８例,胸１０椎体７例,椎体压缩〈１／２椎体高度１３例,〉１／２椎体高度８例,并不全瘫１４例。手术中先行病灶清除,然后哈氏棒内固一,撑开后再次清除病灶,取肋骨和髂骨行椎间及椎板上植骨。术后化疗１２～１５月。结     

Comparison of active and cancer registry-based follow-up for breast cancer in a prospective cohort study

The authors compared the relative effectiveness of two distinct follow-up designs in prospective cohort studies--the active approach, based on direct contact with study subjects, and the passive approach, based on record linkages with population-based cancer registries--utilizing available information from the New York University Women's Health Study (WHS) and the New York State Cancer Registry (NYSCR). The analyses were limited to breast cancer cases identified during the period 1985-1992, for which follow-up was considered reasonably complete by both the WHS and the NYSCR. Among 12,947 cohort members who reported a New York State address, 303 pathologically confirmed cases were identified through active follow-up and 284 through record linkage. Sixty-three percent of cancers were identified by both sources, 21% by the WHS only, and 16% by the NYSCR only. The agreement was appreciably better for invasive cancers. The percentage of cases identified only by the NYSCR was increased among subjects whose active follow-up was incomplete, as well as among nonwhites, obese patients, and parous patients. This suggests that relying on either type of follow-up alone may introduce certain biases in evaluating risk factors for breast cancer. Combining both approaches appears to be a better strategy in prospective cohort studies.     

A method for identifying comparison counties: application to a rural telemedicine evaluation project

The evaluation of telemedicine activity in rural communities is complicated by the fact that most telemedicine sites are chosen because of their existing telecommunications infrastructure and institutional relationships, not by a random selection process. In addition, it is difficult to draw conclusions about the effects of telemedicine without a careful analysis of parallel changes in communities which do not have access to telemedicine services. We have developed a method of identifying comparable counties based on an aggregate measure of health status. A set of 66 variables was collected in a previous project to develop a model to evaluate the relative health status of the population in Missouri. A stepwise regression was used to identify a subset of 15 variables that had the highest predictive value for the health status of a county. Distance measures were then used to identify six counties which were most similar to three telemedicine counties. The method can be used with any study set chosen non-randomly, to identify similar objects that can be used for comparative purposes.