Articles: sepsis.
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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.
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Critical care medicine · Feb 1995
Clinical Trial Controlled Clinical TrialMicrovascular function and rheologic changes in hyperdynamic sepsis.
To investigate the rheologic changes and circulatory abnormalities at the microvascular level during severe sepsis. ⋯ Reactive hyperemia in the forearm is significantly diminished in patients with sepsis, suggesting impaired microvascular blood flow. Rheologic changes, including impaired red blood cell deformability, increased leukocyte aggregation, and endothelial adherence, may contribute to this abnormality by compromising effective capillary cross-sectional area.
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The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation. Early deaths are related primarily to the acute effects of the systemic inflammatory response. ⋯ Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response. Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support.
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Intensive care medicine · Feb 1995
Comparative StudyTreatment of surgical and non-surgical septic multiorgan failure with bicarbonate hemodialysis and sequential hemofiltration.
Hospital mortality of patients with septic multiorgan failure (MOF) is still around 95%. The present study investigates whether this high mortality could be significantly reduced by the addition of sequential hemofiltration (SH) with bicarbonate hemodialysis (HD) to the currently used life supportive measures. ⋯ Mortality observed in this retrospective, uncontrolled study was significantly lower than that currently observed with conventional supportive therapy, with or without the addition of other forms of blood purification, e.g. CAVH and CAVHD. This improvement in results appears to be related to the property of SH to completely clear 90% of the blood from mediators of inflammation in only one passage through the hemofilter, and to better tolerance of HD done using bicarbonate buffer. A definite evaluation of this technique will be eventually reached by a programmed, appropriate sample size study, which is out of reach for one individual ICU.