Hypertension in the elderly: Age- and disease-related complications and therapeutic implications

Summary Effective treatment of hypertension in the elderly requires an understanding of both the progressive course of the disease and the impact of aging on the cardiovascular system, including physiological, genetic, lifestyle, and environmental factors. Review of the literature that has attempted to define the impact of an aging process on cardiovascular structure and function reveals a diversity of findings and interpretations. However, in general, normotensive elderly subjects exhibit the heart and vascular characteristics of muted hypertension, including many features of younger hypertensive patients: cardiac hypertrophy, diminution in resting left ventricular early diastolic filling rate, increased arterial stiffness and aortic impedance, diminution in the baroreceptor reflex, a diminished response to catecholamines and diminished renal blood flow, and an increase in peripheral vascular resistance (PVR). Treatment of elderly hypertensives is more challenging because of the greater likelihood of the presence of concomitant diseases, most importantly, coronary and peripheral atherosclerosis, renal dysfunction, and diabetes mellitus. Isolated systolic hypertension (ISH), the most common form of hypertension in the elderly, has also been clearly shown to be an important predictor of cardiovascular morbidity and mortality, including coronary artery disease, congestive heart failure, and stroke. Treatment of ISH has been shown to lower systolic pressure safely and effectively in the elderly. By reducing PVR, and possibly the arterial stiffness, and thus the early reflected pulse waves, vasodilators, including calcium antagonists, may lower these three components of arterial impedance, and hence lower the arterial load on the heart. The cardiac hypertrophy and reduced left ventricular filling rate associated with hypertension in older individuals can also be ameliorated, to some extent, by calcium channel blockers.Proceedings of a symposium held in Atlanta, Georgia on March 2, 1991.     

Psychological characteristics of males with secondary erectile failure

This study was designed to obtain objective data on the personality profiles of two groups of males with a primary complaint of erectile failure and compare them to a group of psychiatric patients unselected for sexual dysfunction and to a sexually normal control group. Utilizing the Eysenck Personality Inventory, the Institute of Personality and Ability Testing Anxiety Scale, Symptom Checklist, and the Minnesota Multiphasic Personality Inventory, it was determined that males applying to a university/county hospital sex-dysfunction clinic appeared similar to patients seen in the same clinic who were unselected for sex dysfunction and more psychologically disturbed than patients with the same complaint applying for treatment at a private clinic. All three groups showed more psychopathology than sexually normal males. The implications of these findings are discussed.     

Microcomputer voice-response telephone entry for balanced clinical trial randomization

Simple randomization of patients to treatment regimens in clinical trials can result in inbalance among stratum categories. Procedures that produce balance may lack randomness. Systems that are not deterministic yet produce balance are often extremely complex and are not easily performed by randomization clerks. A microcomputer-based voice-response system has been implemented that permits clinic staff to easily randomize patients in clinical trials despite the complexity of the algorithm. Data entry is accomplished by the use of Touch-Tone keys. Input prompts and regimen assignment are spoken by a commercially available voice synthesizer.     

蛋白质芯片技术发现前列腺癌潜在的标志物Pca-24蛋白

目的:应用蛋白质芯片技术寻找前列腺癌标本中的特异性标志蛋白。方法:利用表面增强激光解吸离子化蛋白质质谱分析(Surface-enhancedlaserdesorption/ionization,SELDI)技术,分析22例前列腺癌根治术切除标本中癌组织特有的蛋白质表达谱型。结果:在前列腺癌组织中发现了一个分子量在24,782.56±107.27m/Z的蛋白质,我们暂称其为Pca-24蛋白,此蛋白在17例前列腺癌中16例表达为阳性(94%),在相应前列腺正常组织中无表达;在12例良性前列腺增生中亦无表达。应用激光捕获微解剖挑取肿瘤细胞,我们进一步证实Pca-24蛋白来源于前列腺癌细胞。结论:蛋白质芯片技术对于在组织标本中发现肿瘤标志蛋白是一种有效的工具;Pca-24很可能是一个有用的前列腺癌标志物。     

Stigma, discrimination, and HIV/AIDS knowledge among physicians in Barbados.

OBJECTIVE: To determine the extent of clinical knowledge of HIV/AIDS that physicians in Barbados have and their attitudes towards persons living with HIV/AIDS. METHODS: In 2000 the Barbados Association of Medical Practitioners conducted a survey in order to assess its members' views on HIV/AIDS issues. Over a two-month period 203 physicians (76% of all those practicing in the country) were interviewed. The survey included physicians working in private practice and the public sector. They were surveyed individually concerning their attitudes towards counseling as well as their clinical knowledge, perception of safe practices, fear of occupational exposure, views on ethical issues, experience treating HIV/AIDS patients, and background with HIV/AIDS continuing education. RESULTS: In comparison to physicians who had graduated in later years, physicians who had graduated in 1984 or earlier had seen fewer HIV/AIDS clients, had lower levels of knowledge about the disease, were more likely to test for HIV/AIDS without informed consent, and were less likely to have ever attended a continuing education training course on HIV/AIDS. Overall, knowledge of the clinical indications of HIV/AIDS was low, and 76% of the physicians did not think they had adequate counseling skills. Over 80% of the physicians were comfortable looking after HIV/AIDS patients. While 95% of the physicians would not release HIV test results without a patient's consent, 33% would test, without consent, a seriously ill patient, and 15% would test without consent a patient upon whom they had to perform an invasive procedure if they perceived the patient to be from a high-risk population such as gay men or commercial sex workers. Only 53% of the physicians had attended an HIV/AIDS in-service training program between 1995 and 1999. CONCLUSIONS: Physician training in Barbados should focus on all aspects of HIV/AIDS care, including clinical and emotional factors. Attendance at such training should be mandatory for public sector physicians, and medical school curricula need to be examined to ensure their HIV/AIDS content is current and comprehensive.     

Epidemic parenteral exposure to volatile sulfur-containing compounds at a hemodialysis center.

OBJECTIVE: To determine the cause of acute illness on August 30, 2000, among patients at an outpatient dialysis center (center A). DESIGN: We performed a cohort study of all patients receiving dialysis on August 30, 2000; reviewed dialysis procedures; and analyzed dialysis water samples using microbiologic and chemical assays. SETTING: Dialysis center (center A). PATIENTS: A case-patient was defined as a patient who developed chills within 5 hours after starting hemodialysis at center A on August 30, 2000. RESULTS: Sixteen (36%) of 44 patients at center A met the case definition. All case-patients were hospitalized; 2 died. Besides chills, 15 (94%) of the case-patients experienced nausea; 12 (75%), vomiting; and 4 (25%), fever. Illness was more frequent on the second than the first dialysis shift (16 of 20 vs 0 of 24, P < .001); no other risk factors were identified. The center's water treatment system had received inadequate maintenance and disinfection and a sulfurous odor was noted during sampling of the water from the reverse osmosis (RO) unit. The water had elevated bacterial counts. Volatile sulfur-containing compounds (ie, methanethiol, carbon disulfide, dimethyldisulfide, and sulfur dioxide) were detected by gas chromatography and mass spectrometry in 8 of 12 water samples from the RO unit and in 0 of 28 samples from other areas (P < .001). Results of tests for heavy metals and chloramines were within normal limits. CONCLUSIONS: Parenteral exposure to volatile sulfur-containing compounds, produced under anaerobic conditions in the RO unit, could have caused the outbreak. This investigation demonstrates the importance of appropriate disinfection and maintenance of water treatment systems in hemodialysis centers.     

Continuous exposure to dibromoacetic acid delays pubertal development and compromises sperm quality in the rat.

Previously our work on the haloacid by-products of drinking water disinfection focused on adult exposures. Herein we evaluate the consequence of continuous exposure to dibromoacetic acid (DBA) via drinking water through reproductive development into adulthood. An initial study in which offspring were exposed from gestation day (GD) 15 through adulthood revealed significant delays in preputial separation and vaginal opening, dose-related decreases in the fertility of cauda epididymal sperm, and dose-related diminutions in the sperm membrane protein SP22. Subsequent studies consisted of groups in which exposure ceased on postnatal day 21 (PND 21) versus adulthood. For each exposure, animals were evaluated after puberty (PND 56) as well as at adulthood (PND 120). Exposure to 4, 40, or 400 ppm DBA from GD 15 through PND 21 failed to result in any significant reproductive alterations. By contrast, continuous exposure until adulthood resulted in dose-related alterations consistent with those observed in the dose-finding study. Preputial separation and vaginal opening were delayed 4 and 3 days in males and females exposed to 400 ppm (76.3 mg/kg) DBA. This was associated with increased responsiveness of both the testis and ovary to hCG ex vivo; hCG-stimulated testosterone production by testicular parenchyma on PND 56 was increased at 4 ppm (0.6 mg/kg) DBA and higher. Finally, the quality of proximal cauda epididymal sperm was compromised by continuous exposure to DBA. The sperm membrane proteome was altered in a dose-related manner with SP22, and one of its charged variants, diminished at 40 ppm (3.6 mg/kg) DBA and higher. As more sensitive endpoints are evaluated, lower effect levels can be attributed to haloacid exposure. We are now extending our evaluations to epidemiology studies designed to evaluate sperm quality in men exposed to varying levels of disinfection by-products.     

Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys

In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states.