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71.
The pharmacokinetic and pharmacodynamic properties of nonpeptide angiotensin antagonists in humans are reviewed in this paper. Representatives of this new therapeutic class share common features: lipophilia, intermediate bioavailability, high affinity for plasma proteins and liver metabolism; some have active metabolites. Angiotensin II antagonists block the blood pressure response to exogenous angiotensin II in healthy volunteers, decrease baseline blood pressure in both normal and hypertensive patients, produce a marked rise in plasma renin activity and endogenous angiotensin II and increase renal blood flow without altering glomerular filtration rate. These effects are dose-dependent, but their time course varies between the drugs owing to pharmacokinetic and pharmacodynamic differences. Additionally, the extent of blood pressure reduction is dependent on physiological factors such as sodium and water balance. The characterisation of their pharmacokinetic-pharmacodynamic relationships deserves further refinement for designing optimal therapeutic regimens and proposing dosage adaptations in specific conditions.  相似文献   
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We measured the incidence of cuff retear and injury to the suprascapular nerve after mobilization and repair of a massive rotator cuff tear. Of one hundred four rotator cuff repairs performed over a 5-year period, 10 patients (7 men and 3 women, age range 22 to 68 years) had primary repairs of massive rotator cuff tears requiring cuff mobilization and an acromioplasty as their only procedure. These patients were evaluated at a mean of 2.5 years (range 2.0 to 3.0 years) after surgery. At follow-up electromyographic examination confirmed that 1 of the 10 patients had an iatrogenic suprascapular nerve injury, whereas ultrasound evaluation revealed that 2 of 10 repairs failed. Pain relief was achieved in the eight patients with intact repairs and not in the two with recurrent tears. All patients had some limitation of active motion or strength, especially in external rotation. Thus 7 of 10 patients had neither evidence of nerve injury nor recurrent rotator cuff tears yet still showed limited active motion or weakness. It appears that operative injury to the suprascapular nerve during cuff mobilization can occur, but other factors such as inadequate cuff muscle function are more frequently responsible for the poor functional outcomes seen after successful repairs of massive rotator cuff tears.  相似文献   
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Genome-wide scans for linkage of chromosome regions to type 1 diabetes in affected sib pair families have revealed that the major susceptibility locus resides within the major histocompatibility complex (MHC) on chromosome 6p21 (lambda s = 2.5). It is recognised that the MHC contains multiple susceptibility loci (referred to collectively as IDDM1), including the class II antigen receptor genes, which control the major pathological feature of the disease: T lymphocyte-mediated autoimmune destruction of the insulin-producing pancreatic beta cells. However, the MHC genes, and a second locus, the insulin gene minisatellite on chromosome 11p15 (IDDM2; lambda s = 1.25), cannot account for all of the observed clustering of disease in families (lambda s = 15), and the scans suggested the presence of other susceptibility loci scattered throughout the genome. There are four additional loci for which there is currently sufficient evidence from linkage and association studies to justify fine mapping experiments: IDDM4 (FGF3/11q13), IDDM5 (ESR/6q22), IDDM8 (D6S281/6q27) and IDDM12 (CTLA-4/2q33), IDDM4, 5 and 8 were detected by genome scanning, and IDDM12 by a candidate gene strategy. The results suggest that the clustering of type 1 diabetes in families is due to the sharing of alleles at multiple loci, and that the as yet unidentified environmental factors are not causing clustering, but instead appear to influence the overall penetrance of genetically programmed susceptibility. The data are consistent with a polygenic threshold model for the inheritance of type 1 diabetes.  相似文献   
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The present study's aims are to search for the presence of interleukin-6 bioactivity (IL-6) in medium conditioned by various testicular cell types and to investigate the cellular and hormonal regulation of testicular IL-6 production. Sertoli cells prepared from rats of increasing ages (20, 35, and 45 days) secreted IL-6 in vitro, whereas medium conditioned by pachytene spermatocytes, early spermatids, and peritubular cells showed no activity. Lipopolysaccharide (LPS) and latex beads, two known stimulators of monocyte/macrophage IL-6 production, markedly stimulated IL-6 secretion by Sertoli cells at all the ages investigated. Maximum levels of IL-6 were reached after 6 h of culture of Sertoli cells with LPS and after 24 h with latex beads. When Sertoli cells were cocultured with pachytene spermatocytes, early spermatids, or fractions containing residual bodies and cytoplasts from elongated spermatids, only the latter significantly stimulated IL-6 levels. Maximum levels of IL-6 were attained by adding 2 x 10(6) residual bodies to Sertoli cells; a significant increase in IL-6 secretion was seen after 6 h, and maximum levels were observed after 24 h. The levels of IL-6 varied throughout different stages of the seminiferous epithelium cycle; highest levels were observed in stages II-VI and lowest in stages VII-VIII. IL-6 bioactivities induced by LPS and residual bodies and cytoplasts from elongated spermatids could be totally neutralized with a specific monoclonal antibody at all of the ages studied. FSH, phorbol myristate acetate, and IL-1 alpha augmented Sertoli cell IL-6 secretion in a dose-dependent manner. Furthermore, FSH and (Bu)2cAMP differentially stimulated IL-6 secretion during the seminiferous epithelial cycle. It is concluded that the release of IL-6 from Sertoli cells is regulated by a complex interplay between residual bodies and humoral factors.  相似文献   
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OBJECTIVE: It is commonly believed that the full moon exerts an influence on violence and aggression in psychiatric settings. The literature to date is contentious. This study used a robust methodology to examine the hypothesis that there was an increased frequency of violent and aggressive behaviour among hospitalised psychiatric clients at the time of the full moon. METHOD: Prospective data were collected in five inpatient psychiatric settings across the Northern Sydney Area Health Service. Morrison's hierarchy of violence and aggression was used to rate behaviour. Lunar phases were clearly defined and Poisson regression used to examine relationships between lunar phase and violence. Extraneous temporal variation was considered. RESULTS: No significant relationship was found between total violence and aggression or level of violence and aggression and any phase of the moon. CONCLUSION: Future research could profitably examine the implications of a belief in the lunar effect among health workers in the face of evidence that no relationship exists between violence, aggression and the lunar cycle.  相似文献   
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Multimedia Tools and Applications - The interest in real-time micro-expression recognition has increased with the current trend in human-computer interaction applications. Presently, there are...  相似文献   
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