Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Immunosuppression following injury influences infectious morbidity and mortality. Impaired T-cell activation conceding to inadequate antigen recognition contributes to this immunosuppression. Successful activation and proliferation of T-cells requires precisely specified levels of intracellular calcium thresholds and peak signals. ⋯ Suppression of calcium signaling appears to be mediated by at least, in part, circulating serum factors. Prostaglandin E2 seems to have a limited contribution to this effect as it is suppressive only when in direct contact with PBMC. Immune cell activation failure can in part be explained by the inadequacy of calcium signaling; restoration of immunocompetence following trauma will have to be addressed by strategies to restore calcium signaling, a vital step necessary for T-cell proliferation following antigen recognition.
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Clinical Trial Controlled Clinical Trial
Repeated administration of a F(ab')2 fragment of an anti-tumor necrosis factor alpha monoclonal antibody in patients with severe sepsis: effects on the cardiovascular system and cytokine levels.
In an uncontrolled clinical trial the effects of repeated administration of the F(ab')2 fragment of a murine monoclonal anti-tumor necrosis factor alpha (TNF alpha)-antibody (MAK 195F) on cytokine levels and the cardiovascular system were studied in 20 patients with severe sepsis. Patients were treated with a total of 11 single dosages of the anti-TNF alpha-antibody intravenously over 5 days using either 1 mg/kg (n = 10) or 3 mg/kg (n = 10). ⋯ Comparison of our data with recent data from phase I or II trials using a complete murine monoclonal anti-TNF alpha-antibody suggest that the F(ab')2 fragments of the murine monoclonal anti-TNF alpha-antibody may be of similar efficacy. Definitive conclusions, however, with respect to improvement of mortality and improvement of the cardiovascular system, await the results of larger ongoing placebo-controlled trials.
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Comparative Study
Comparative effects of 7% NaCl in 6% dextran 70 and 0.9% NaCl on oxygen transport in endotoxemic dogs.
We compared the effects of 7% NaCl in 6% dextran 70 (HSD) and 0.9% NaCl (IS) resuscitation of endotoxic dogs on hemodynamic and cardiorespiratory parameters and the oxygen consumption-delivery relationship. Escherichia coli endotoxin (3 mg.kg-1, intravenously) was infused over 5 min into 13 paralyzed, chloralose-anesthetized, splenectomized dogs. Six additional dogs received a sham endotoxin infusion (saline) and served as controls. ⋯ The total volume of HSD administered averaged 10.0 +/- 0.2 ml.kg-1 which was significantly less than the volume of IS, which averaged 67.2 +/- 9.3 ml.kg-1. Incremental hemorrhages (2-5 ml.kg-1) were then performed in all dogs to determine the oxygen consumption-delivery relationship and the critical level of oxygen delivery (DO2Crit). The average DO2Crit values of the HSD, IS, and control groups were 9.42, 9.15, and 6.82 ml.min-1.kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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The sequence of injury determines the degree of lung damage in both inhalation and thermal injuries.
The lung damage resulting from smoke inhalation is an important determinant of morbidity and mortality in thermally injured patients. We hypothesized that the degree of pulmonary microvascular damage seen with smoke inhalation could be affected by whether the smoke insult preceded or followed thermal injury. ⋯ Lung lymph flow and wet/dry weight ratio were significantly higher in smoke before burn group animals. We conclude that lung damage is minimized when thermal injury precedes smoke inhalation injury.
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This study assessed the hepatic acute phase response and cellular Ca2+ regulation in septic animals and in hepatoma cell lines in vitro. Sepsis was induced in male Sprague-Dawley rats by implanting in their abdominal cavities fecal pellets impregnated with live Escherichia coli and Bacteroides fragilis. 8 h after implantations, rats were treated with diltiazem (1.2 mg/kg) or superoxide dismutase (SOD) (5 x 10(3) units/kg). After 24 h, plasma acute phase proteins (APP) were determined by immunoelectrophoresis, and hepatic APP-mRNAs by Northern blot hybridization. ⋯ Because diltiazem was previously shown to prevent sepsis-related disturbances in hepatic cellular Ca2+ regulation, its mediation of decrease in APP, systemic/metabolic response, and mortality may be effected through modifications in cellular Ca2+ regulation. The data from hepatoma cells show an attenuation of the AAP can result from direct effects of a calcium blocker. However, whether the blocker primarily modifies cellular Ca2+ regulation and secondarily effects APP gene expression, or directly effects gene expression remains unknown.