Articles: sepsis.
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Mortality from septic shock is considerable despite the advantages of cardiovascular support and antibiotic therapy. This article reviews current therapy of septic shock including immunotherapy and further possibilities of septic shock treatment. The role of cytokines, their inhibitors and antibodies to endotoxin is mentioned. Although these treatments hold much promise for the future, careful evaluation of both the benefits and complications of therapy is needed before widespread clinical use can be recommended.
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Using animal models or healthy volunteers, injection of lipopolysaccharide (LPS) or bacteria causes activation of macrophages with excessive synthesis and secretion of proinflammatory cytokines. Although these models mimic the effects of LPS in the host, they may represent more of an experimental expression of endotoxemia than natural infection itself. Therefore, as an ex vivo model of sepsis, whole blood from 15 patients with severe sepsis and 20 control patients without infection was stimulated with LPS to study the kinetics of mRNA expression and release of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6. ⋯ While IL-1 beta mRNA expression was similar in peripheral blood mononuclear cells (PBMCs) harvested from LPS-stimulated whole blood in septic and control patients, the half-life and consequently the expression of TNF-alpha and IL-6 mRNA were strongly reduced in the septic group. These data indicate a downregulatory mechanism of cytokine release in whole blood from patients with severe sepsis that occurs on different levels. Although excessive secretion of proinflammatory cytokines has been considered deleterious for the host, the reduced capacity of PBMCs in whole blood from septic patients to synthesize and secrete proinflammatory cytokines to an inflammatory stimulus may result in immunodeficiency, because these cytokines in low concentrations are involved in the upregulation of essential cellular and humoral immune functions.
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To develop customized versions of the Simplified Acute Physiology Score II (SAPS II) and the 24-hour Mortality Probability Model II (MPM II) to estimate the probability of mortality for intensive care unit patients with early severe sepsis. ⋯ Customization provides a simple technique to apply existing models to a subgroup of patients. Accurately assessing the probability of hospital mortality is a useful adjunct for clinical trials.