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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial antimicrobial susceptibility predictors such as the minimal inhibitory concentration (MIC) assay and Nathans Agar Well Diffusion (NAWD) assay provide essential information relevant to the therapeutic approach in burn-wound sepsis. The susceptibilities of 68 gram-positive burn-wound isolates were tested against topical Bactroban (mupirocin) (Beecham Laboratories, Bristol, Tenn.) and compared with other topical antimicrobials such as mafenide acetate, silver sulfadiazine, and bacitracin/neomycin/polymyxin (BNP). Topical susceptibility data were obtained with a modification of NAWD assay. Bactroban's antimicrobial activity was greater than that of mafenide acetate (100% vs 97%), and significantly greater than that of silver sulfadiazine and that of BNP (p less than 0.001). Of the 68 isolates that were susceptible to Bactroban, 51 were predominately methicillin-resistant staphylococci (MRSA). Bactroban showed in vitro activity against 71% of the 85 gram-negative isolates tested. Mafenide acetate showed activity against 89% of these isolates, a significant difference compared with Bactroban (p less than 0.02). In general, no significant difference was found between the activities of Bactroban and silver sulfadiazine against the gram-negative isolates. The activities of mafenide acetate and silver sulfadiazine against isolates of Pseudomonas aeruginosa were significantly greater than that of Bactroban (p less than 0.05). Bactroban may be used in the treatment of documented staphylococcal burn-wound infections. On the basis of the in vitro data, 13 patients with MRSA burn-wound infections susceptible to Bactroban were evaluated. Quantitative wound biopsies were employed to determine the efficacy of this therapeutic approach. The outcome of these infections was correctly predicted by the NAWD assay in 92.3% of the patients treated (p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Topical Bactroban (mupirocin): efficacy in treating burn wounds infected with methicillin-resistant staphylococci. 212 3

Tissue factor is the initiator of the extrinsic coagulation pathway and is an important regulator of haemostasis. Tissue factor is constitutively expressed in numerous cells and tissues, and can be induced in monocytes and endothelial cells by different inflammatory agents. Lymphocytes and serum factors can modulate the expression of tissue factor in monocytes. The regulation of tissue factor expression in monocytes appears to be different from that in endothelial cells. Phorbol myristate acetate can inhibit as well as induce tissue factor activity in monocytes, whereas phorbol myristate acetate only induces the expression of tissue factor in endothelial cells. Tissue factor expression in monocytes from patients with infections is not always associated with DIC. The extrinsic pathway inhibitor may play a role in the development of DIC in patients with sepsis. Deposition of extravascular fibrin may be an important determinant of tissue injury.
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PMID:Cellular regulation of tissue factor. 213 17

Despite numerous reports, the role of tumor necrosis factor (TNF) in polymorphonuclear leukocyte (PMN) function remains controversial. We found TNF to be a potent, pertussis toxin-independent stimulator of PMN adhesion (ED50 2.6 pM). TNF-stimulated PMN under adherent conditions released up to 65% of their transcobalamine content (ED50 3.9 pM) and increased their burst activity 10-fold (ED50 3.2 pM) as measured by the hexose monophosphate shunt, whereas PMN held in suspension hardly degranulated at all and only little burst activity was demonstrable. However, preincubation of PMN with TNF in suspension led to a decrease in cellular adhesiveness, degranulation, and burst activity in response to a secondary stimulus of TNF under adherent conditions, although cells remained fully responsive toward phorbol myristate acetate. A concomitant dose-dependent decline of TNF receptor numbers that correlated well with the inhibition of PMN function (r = 0.91) suggests receptor down-regulation as the mechanism of functional PMN deactivation. Remarkably, preincubation with other PMN stimuli such as N-formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, leukotriene B4, complement component fragment 5a (C5a)/C5a (desarginated), and endotoxin also led to a reduction of TNF-specific PMN responses (cross-deactivation) from 35% (LTB4) to 90% (endotoxin), corresponding with the down-regulation of TNF receptors. Deactivation and receptor down-regulation are independent of pertussis toxin-sensitive G proteins and protein kinase C but seemed to depend on changes in calcium metabolism. Granulocyte hyporesponsiveness towards TNF in sepsis (with elevated blood levels of endotoxin and TNF) might be a mechanism of self-protection or, to the contrary, might impair a possibly central mode of host defense.
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PMID:The tumor necrosis factor receptor and human neutrophil function. Deactivation and cross-deactivation of tumor necrosis factor-induced neutrophil responses by receptor down-regulation. 216 42

Five cancer patients undergoing intravenous infusions of human recombinant tumor necrosis factor (TNF)alpha were evaluated for the effects these infusions had on the priming of circulating neutrophils for hypochlorous acid (HOCl) production. These patients were also studied for changes in temperature, circulating white blood cell counts, blood pressure, and spontaneous monocyte interleukin 1 beta (IL-1 beta) and TNF production. As predicted by previous in vitro studies, patient neutrophils increased their HOCl production to unopsonized zymosan from a baseline of 29.2 +/- 5.9 nmol I- oxidized/4 x 10(6) cells to a peak of 64.2 +/- 9.8 nmol I- oxidized/4 x 10(6) cells at 4 h after TNF infusion (P less than 0.01). Similar increases were also seen at 4 h with phorbol myristic acetate and opsonized zymosan as the stimuli. The priming effect could be reproduced in neutrophils from a normal individual by incubating them with the 30-min serum samples from the infused patients. The ability of this serum to prime neutrophils was completely blocked by a monoclonal anti-TNF alpha-antibody but not by an anti-IL-1 beta antibody. In addition to the priming of their neutrophils, patients also experienced fever, marked hypotension, and an initial fall, followed by rebound to an elevation, in circulating white blood cell counts. The TNF infusions did not produce detectable circulating IL-1 beta nor did they induce significant production of TNF or IL-1 beta by circulating blood monocytes. These studies confirm the role of TNF in producing the signs of sepsis such as hypotension, fever, and leukopenia followed by leukocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor infusions in humans prime neutrophils for hypochlorous acid production. 217 55

A randomized, double-blind study to determine the effect of intramuscular vitamin E on mortality and intracranial hemorrhage (ICH) was performed. One hundred forty-nine neonates with birth weights less than or equal to 1000 g and less than or equal to 24 hours of age were grouped by weight (501 to 750 g and 751 to 1000 g) and randomized to treatment or control. The treatment group received intramuscular injections of vitamin E (dl-alpha-tocopherol) on days 1, 2, 4, and 6 of life. The control group received intramuscular injections of placebo on the same schedule. All neonates initially received oral vitamin E (100 mg/kg/day dl-alpha-tocopheryl acetate), which was subsequently adjusted to keep serum levels at 0.5 to 3.5 mg/dL. Ultrasonographic examinations of the head were performed as possible on days 1, 5 to 7, and 12 to 14. Hemorrhage was defined as mild if less than or equal to grade II ICH, or severe if grade III or IV. No significant differences in neonatal or total hospital mortality between groups were found. However, all ICH, as well as severe ICH, were significantly less in the vitamin E-treated 501 to 750-g subgroup (all ICH: 60% vs 29%; severe ICH: 32% vs 4%). When survivors were analyzed separately, a significant decrease in severe ICH was seen in the vitamin E-treated neonates (25% vs 5%). Necrotizing enterocolitis and sepsis did not occur more frequently in the neonates treated with intramuscular injections of vitamin E. Other than two cases of mild induration at injection sites, no deleterious side effects of treatment were identified. Vitamin E may have a role in the prevention of severe ICH in premature neonates weighing between 501 and 750 g.
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PMID:Effect of intramuscular vitamin E on mortality and intracranial hemorrhage in neonates of 1000 grams or less. 217 50

Six cats (Nos. 1-6) were inoculated intramuscularly with (1 x 10(6)) and orally (5 x 10(5)) tachyzoites of Neospora caninum. Three (Nos. 1-3) of the six cats were given 40 mg/kg methylprednisolone acetate 7 days before and on the day of inoculation with N. caninum tachyzoites, and three cats (Nos. 4-6) were not given methylprednisolone acetate. Two of the cats (cat Nos. 1 and 2) given methylprednisolone acetate died suddenly. Cat No. 1 died 8 days post-inoculation, and cat No. 2 died 16 days post-inoculation. Cat No. 3 was euthanatized 21 days post-inoculation. Cat No. 1 had lesions of gram-positive bacterial septicemia. Necrotizing encephalitis, myelitis, disseminated skeletal muscle necrosis, hepatic necrosis, interstitial pneumonia, and renal tubular necrosis were the main lesions in cat Nos. 2 and 3. The cats that were not given methylprednisolone acetate remained clinically normal except for slight weight loss in cat No. 6. All three of these cats were euthanatized 55 days post-inoculation. Mild myositis and encephalitis were noted on microscopic examination of tissues from these three cats. Neuromuscular lesions were not seen in six control cats (Nos. 7-12) not inoculated with N. caninum and euthanatized 21 or 22 days after administration of the first two doses of methylprednisolone acetate (40 mg/kg), given at a weekly interval.
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PMID:Neosporosis in cats. 223 86

In pursuing the mechanism of endotoxin action, we examined the effect of lipopolysaccharide (LPS) and its chemically defined components, lipid A and lipid X on cultured bovine endothelial cells. We report that LPS and lipid A caused detachment and altered morphology of endothelial cells while lipid X did not. Phorbol myristate acetate, a compound known to activate protein kinase C, also caused endothelial cell detachment. Morphologic changes were readily apparent in the endothelial cells after 6 hours of exposure to lipopolysaccharide (1 microgram/ml); at that time many of the cells had contracted and formed bleblike structures on the surface. Large vacuoles, dense bodies, and pyknotic nuclei were found in the detaching cells, indicating necrosis or cell death. Preceding the morphologic changes and actual detachment, endothelial cell DNA and RNA synthesis was impaired by LPS. The changes in DNA and RNA synthesis occurred within 4 hours of exposure to 1 microgram/ml of LPS when the cells were still able to maintain normal levels of ATP. In addition to the inhibition of nucleic acid synthesis, protein synthesis was inhibited after 6 and 8 hours of LPS exposure. DNA, RNA, and protein synthesis returned to control levels after 24 hours of exposure. Investigation on the cultured bovine endothelial cells as a model for LPS action was useful in that these cells are sensitive to relatively low levels of LPS and the endothelium may be an important target in sepsis.
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PMID:Effects of lipopolysaccharide, lipid A, lipid X, and phorbol ester on cultured bovine endothelial cells. 245 32

Kupffer cell control of hepatocyte protein synthesis may be an important mechanism involved in the regulation of normal liver function and may be one mechanism responsible for the alterations in liver function seen during sepsis. The present series of in vitro experiments compare the response to various inflammatory stimuli of hepatocytes cocultured with Kupffer cells with that of hepatocytes cultured alone. In the absence of inflammatory stimuli, Kupffer cells stimulated hepatocyte protein synthesis. Lipopolysaccharide or gentamicin-killed Escherichia coli triggered Kupffer cell-mediated inhibition of cocultured hepatocyte protein synthesis but had no effect on protein synthesis of hepatocytes cultured alone. Phorbol myristate acetate, muramyl dipeptide, and calcium ionophore had no effect on hepatocytes cultured alone but resulted in a loss of Kupffer cell-mediated stimulation of cocultured hepatocyte protein synthesis without inhibition. Addition of dexamethasone to cocultures prevented the Kupffer cell-mediated inhibition of hepatocyte protein synthesis triggered by lipopolysaccharide, but did not block Kupffer cell-mediated stimulation in the absence of lipopolysaccharide. The data suggest that Kupffer cells can stimulate and inhibit hepatocyte protein synthesis by independent mechanisms. Kupffer cells may be important regulators of hepatocellular function in health and disease.
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PMID:Evidence that rat Kupffer cells stimulate and inhibit hepatocyte protein synthesis in vitro by different mechanisms. 249 43

Neutrophils can be "primed" for an enhanced respiratory burst by lipopolysaccharide (LPS) in concentrations measurable in patients with septic shock. Leukotriene B4 (LTB4) is the primary eicosanoid product of neutrophils and is felt to be a mediator of host defense and inflammation. We investigated the in vitro effects of LPS on neutrophil production of LTB4 and the omega-oxidation metabolites of LTB4. Incubation of neutrophils with LPS in concentrations ranging from 0.01 to 100 ng/ml did not result in production of LTB4 or metabolites in the absence of a second stimulus. Priming neutrophils with LPS and then stimulating with opsonized zymosan, phorbol-myristate-acetate or a low concentration of the calcium ionophore A23187 resulted in enhanced production of LTB4. LPS priming of neutrophils occurred in a concentration dependent manner. LPS did not result in LTB4 production in response to the chemoattractant peptide FMLP. LPS priming of neutrophils had no effect on cytosolic calcium concentrations of resting or zymosan-stimulated cells. These results suggest that LPS might effect host defense and tissue injury by potentiating the effect of other stimulants on neutrophil production of LTB4. This LPS induced enhancement may represent an important pathogenetic pathway in patients with gram negative sepsis.
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PMID:Bacterial lipopolysaccharides prime human neutrophils for enhanced production of leukotriene B4. 253 52

We have shown previously that fluid phase platelet-activating factor (PAF) can enhance or "prime" polymorphonuclear (PMN) responses to subsequent stimulation with agonists such as formyl-methionine-leucine-phenylalanine (FMLP). Since thrombin induces PAF production in endothelial cells, we tested whether this thrombin-provoked endothelial PAF primes responses of marginated PMNs. Monolayers of human umbilical vein endothelial cells were exposed to either thrombin (0.5-5.0 units/ml) or buffer for up to 5 min and then PMNs were layered on top of the endothelial cells. After a further 5 min incubation, the PMNs were stimulated with a suboptimal concentration of FMLP (10(-7) M), and their superoxide production, elastase release, adhesion to endothelium, and capacity to cause endothelial cell lysis and detachment were assessed. Thrombin pretreatment significantly enhanced each of these FMLP-stimulated neutrophil responses. The extent of this enhancement correlated with both the dose and duration of thrombin treatment of endothelial cells and also the duration of PMN incubation with thrombin-exposed endothelium. Evidence that the augmentation was due to endothelial-derived PAF was obtained as follows: (1) thrombin induced [3H]acetate incorporation into endothelial PAF (assayed in lipid extracts); (2) antithrombin III conjointly inhibited this [3H]acetate uptake and prevented the priming effect of thrombin-treated endothelium on PMN responses; and (3) the PAF receptor antagonist BN52021, when preincubated with PMNs, also effectively blocked the enhancement of PMN responses. We conclude that thrombin stimulation of endothelial cells initiates a sequence of events culminating in the production of PAF--a membrane phospholipid capable of priming marginated PMNs. We suggest that this coagulation-fostered endothelial/PMN interaction may underlie a paracrine response that may potentiate PMN-mediated endothelial injury during sepsis and other thrombin-generating disorders.
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PMID:Thrombin-treated endothelium primes neutrophil functions: inhibition by platelet-activating factor receptor antagonists. 254 22


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