Articles: sepsis.
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The in vivo efficacy of three cell wall-active antibiotics, imipenem, meropenem, and ceftazidime, was compared in mice rendered hypersusceptible to the pathophysiologic effects of lipopolysaccharide by treatment with D-galactosamine. When CF-1 mice were administered Escherichia coli, D-galactosamine, and saline intraperitoneally, an LD50 was achieved at an inoculum of approximately 2 x 10(4) cfu. ⋯ When the dose of antibiotic was decreased to 2 mg/kg, neither meropenem nor ceftazidime could provide measurable protection, whereas imipenem was almost fully protective (P < .002). These differences in protective efficacy were also noted with experimental Pseudomonas aeruginosa but not Staphylococcus aureus infection.
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Traditionally, sepsis is defined as a systemic inflammatory reaction of the organism to Gram-negative bacterial leading to septic shock--characterized by hemodynamic derangements--and eventually to septic multi-organ malfunction. Sepsis syndrome is diagnosed when fever and other abnormalities of vital signs are present along with abnormalities of one or more organ systems that are not the site of infection and trauma (but with an identifiable locus of infection), and is associated with a range of 30% to 50% mortality. In the United States, one of the most frequent and serious problems confronting clinicians is the management of a serious infection and the systemic response to the infection, such as sepsis. ⋯ Calcium plays vital roles in the intracellular regulation of a variety of cellular responses (for example, contraction, secretion, cell-cell communication, cell proliferation) under physiologic conditions in various cell-types. Alterations in intracellular Ca2+ regulation leading to elevated cytosolic Ca2+ concentration could not only interfere with the cellular responses but also activate lytic enzymes such as proteinases and phospholipases. The objective of this article is to discuss the experimental findings that indicates relationship between alterations in cellular signaling and protein metabolic derangements in non-immune cells (skeletal muscle or liver) during sepsis and inflammation.
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Endotoxin (ETX) is thought to be the primary inducer of proinflammatory mediator release associated with bacterial sepsis. Furthermore, a number of studies indicate that preexposure of animals to high doses of ETX produces macrophages (M luminal diameters) that are refractory to ex vivo stimulation with ETX. However, it is unknown if levels of ETX comparable to those typically encountered in sepsis induce a similar refractory state in M luminal diameters. ⋯ Bacterial component(s) other than ETX per se induces the sustained dysfunction in PM luminal diameter capacity to produce proinflammatory cytokines during sepsis and/or peritonitis. Thus, agents directed against ETX alone may not be adequate in the treatment of polymicrobial sepsis.
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Small-volume resuscitation by means of bolus infusion of hypertonic saline solutions was first applied for the primary treatment of severe hemorrhagic and traumatic shock and promptly restored central hemodynamics and regional organ blood flow. Mechanisms of action are diverse--i. maintenance of high cardiac output (direct myocardial stimulation; increase in intravascular volume); ii. maintenance of peripheral arterial vasodilation (effect of hyperosmolality; plasma volume effect) and iii. reduction of tissue edema (shifting of tissue water along the osmotic gradient). ⋯ Hypertonic volume therapy has been the object of several experimental studies of acute hyperdynamic endotoxemia, however, a greater number of clinical studies have to be developed for the better understanding of the positive, and perhaps hazardous, effects of small-volume resuscitation in sepsis and multiple organ failure. The aim of this paper is to review the concepts involving such solutions, and their potential use in treatment of profound hypovolemia and microcirculatory deterioration associated with sepsis and endotoxic shock.