The American journal of the medical sciences
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When compared with other U.S. populations, African Americans have excess hypertension. Genetic variants in elements of the renin-angiotensin-aldosterone system (RAAS), namely the angiotensin-converting enzyme (ACE), aldosterone synthase (CYP11B2), and angiotensin II type 1 receptor (AGTR1) genes, have been associated with risk of hypertension in some populations. ⋯ These data suggest that the (-535)T allele of AGTR1 and (-344)T allele of CYP11B2 may increase hypertension risk among African Americans but not among Latinos. Characterization of the linkage disequilibrium and haplotype patterns in the RAAS pathway genes will be crucial to understanding differences in hypertension susceptibility in these ethnic populations.
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Extrapulmonary small-cell carcinoma arising in the prostate gland has been described in several case series and case reports. However, pure small-cell carcinoma of the prostate is rare, and there are only a few reports in literature describing the clinical features and management of this neoplasm. These tumors are highly aggressive and commonly manifest with visceral metastasis at the time of diagnosis. We report a case of metastatic pure prostatic small-cell carcinoma and an associated paraneoplastic polyneuropathy.
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Based on the results of the phase III PROWESS trial, recombinant human activated protein C (rhAPC) was approved by the Food and Drug Administration (FDA) for use in severely septic patients. Concerns regarding rhAPC's inconsistent effects, incomplete understanding of its mechanism of action, and its safety in particular subgroups were raised during the FDA's evaluation. This study attempts to assess the cost-effectiveness rhAPC by comparing its effects during recent clinical use to its prior phase III trial testing and by considering other potentially less expensive treatments with effects that may overlap those of rhAPC. ⋯ Many of the patients receiving rhAPC during clinical use may have otherwise been excluded from its phase III trial testing. Data from several recent phase III trials as well as a recent meta-analysis suggest that heparin and physiologic dose steroids offer substantially less expensive alternatives to rhAPC. Further phase IV testing will be required to confirm such possibilities.
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Coagulopathy and systemic inflammation are almost universal in patients with severe sepsis. Interaction between the two results in an intense inflammatory response and microthrombi formation in the vessels of multiple organs, resulting in organ dysfunction or severe sepsis. Recombinant human activated protein C, also known as drotrecogin alfa (activated), possesses anti-inflammatory, antithrombotic, and profibrinolytic properties. ⋯ An increased risk of bleeding during the infusion was the only side effect experienced. Recent data demonstrate that early administration of drotrecogin alfa (activated) is associated with lower mortality rates. Despite concern over its relatively high cost, analysis has demonstrated that recombinant human activated protein C is as cost-effective as other commonly used treatments in the intensive care unit.
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Activation of the coagulation cascade during invasive infection can result in purpura fulminans, with rapid progression of tissue ischemia, or may manifest as abnormal clotting indices alone. Although severe derangements in coagulation are associated with organ dysfunction and increased mortality, the contribution of coagulopathy to the pathophysiology of sepsis remains incompletely understood. ⋯ Clinical observations during treatment of septic patients with the endogenous anticoagulant activated protein C have stimulated additional study of interactions between endothelial injury, coagulation, and inflammation. This review describes clotting abnormalities during sepsis and discusses the clinical experience with therapeutic strategies intended to oppose excessive coagulation.