The Journal of infectious diseases
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Leptin production is increased in rodents by administration of endotoxin or cytokines. To investigate whether circulating leptin is related to cytokine release and survival in human sepsis, plasma concentrations of leptin, interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, soluble TNF receptor type I, IL-1 receptor antagonist (IL-1ra), and the inflammatory modulator IL-10 were measured as soon as severe sepsis (n=28) or septic shock (n=14) developed and every 6 h for 24 h. ⋯ By discriminant analysis, leptin and IL-6 were independent predictors of death. These findings suggest that increases in leptin levels may be a host defense mechanism during sepsis.
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Multicenter Study Clinical Trial
Microbiologic findings and correlations with serum tumor necrosis factor-alpha in patients with severe sepsis and septic shock.
To understand the microbiology of sepsis and its relationship with tumor necrosis factor (TNF)-alpha, 444 septic patients were studied in a phase II clinical trial. In total, 270 (61%) 444 of episodes were microbiologically documented. The most common isolates were Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. ⋯ Patients with a positive culture had significantly higher TNF-alpha levels (65.9 vs. 29.2 pg/mL, P=.0001). Patients with a pure gram-negative infection had significantly higher TNF-alpha levels than those with a pure gram-positive or mixed infection, especially in the late shock group (142.6, 64.0, and 52.8 pg/mL, respectively, P=.004). These results provide further support for the concept that patients with sepsis are a heterogeneous group that require more precise definition.
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The administration of reference endotoxin (Escherichia coli O:113, Lot EC-5) to humans has been an important means to study inflammation in vivo; however, the supply of Lot EC-5 is depleted. A new lot of reference endotoxin (Clinical Center reference endotoxin [CCRE]), derived from the original bulk material extracted from E. coli O:113, was processed. ⋯ These responses were attenuated (all P<.012) in subjects given Lot EC-5 (4 ng/kg) in comparison with those in subjects given CCRE, showing that, over several years, EC-5 had lost potency. Thus, in healthy subjects, the magnitude of exposure to CCRE results in a graded dose response of major components of innate immunity.
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Review Comparative Study
Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: comparisons and potential for use in the treatment of infections in nonneutropenic patients.
Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhance the antimicrobial functions of mature neutrophils. G-CSF differs from GM-CSF in its specificity of action on developing and mature neutrophils, its effects on neutrophil kinetics, and its toxicity profile. The toxicity profile of recombinant (r) GM-CSF is consistent with priming of macrophages for increased formation and release of inflammatory cytokines, whereas rG-CSF induces production of antiinflammatory factors, such as interleukin-1 receptor antagonist and soluble tumor necrosis factor receptors, and is protective against endotoxin- and sepsis-induced organ injury. The low toxicity of rG-CSF, results of animal models of infection, and extensive experience with neutropenic subjects have promoted clinical studies in nonneutropenic subjects, which indicate that rG-CSF may be beneficial as adjunctive therapy for treatment of serious bacterial and opportunistic fungal infections in nonneutropenic patients, including those with alterations in neutrophil function.
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Fifteen (14%) of 105 women with Ebola hemorrhagic fever hospitalized in the isolation unit of the Kikwit General Hospital (Democratic Republic of the Congo) were pregnant. In 10 women (66%) the pregnancy ended with an abortion. In 3 of them, a curettage was performed, and all 3 received a blood transfusion from an apparently healthy person. ⋯ All women presented with severe bleeding. Only 1 survived; she had a curettage because of an incomplete abortion after 8 months of amenorrhea. The mortality among pregnant women with Ebola hemorrhagic fever (95.5%) was slightly but not significantly higher than the overall mortality observed during the Ebola epidemic in Kikwit (77%; 245/316 infected persons).