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

The intranasal inoculation of adult mice with saline suspensions of virulent group B streptococci serotype Ia resulted in septicemia which was lethal. Decreasing the inoculation dose of streptotocci increased the time required for their appearance in the blood and the mean time to death of the mice. Before the appearance of septicemia, the number of organisms in the lungs decreased to about 1% of the inoculation dose, and the majority could be recovered by lavage of the lungs through the trachea. In contrast, most of the organisms remained in the lavaged lungs of bacteremic mice after intranasal or intravenous inoculation. Lung surfactant obtained from infected mice was altered by a reduction in lipid and by an increase in protein. The organisms in vitro did not attack surfactant lipid labeled with [1-14C]palmitic acid, but their pathogenesis in vivo affected the permeability of the air-blood barrier, as shown by the leakage into the air spaces of plasma albumin labeled by the intravenous injection of Evans blue dye.
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PMID:Group B streptococcal type Ia sepsis in mice after intranasal inoculation and the effect of infection on lungs. 38 6

The purpose of this study was to test the hypothesis that different hepatocellular functions are regulated individually during sepsis. This was done by simultaneously measuring bile production, release of liver transaminases, and synthesis of secreted proteins in perfused livers from control and septic rats. Sepsis was induced by cecal ligation and puncture (CLP); control rats were sham-operated. After 16 hours, livers were perfused in situ, and bile flow, synthesis rates of albumin and alpha 1-acid glycoprotein (a major acute-phase protein in rats), and release of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) into perfusate were determined. Within the same livers, sepsis resulted in a 54% increase in the synthesis of alpha 1-acid glycoprotein and approximately 30% inhibition of albumin synthesis concomitant with 50% lower bile flow. The concentrations of GOT and GPT in the perfusate increased slightly during the experiments, both when control and septic livers were perfused. The maintained tissue levels of adenosine triphosphate (ATP) and the uptake of Evans blue dye by less than 1% of the hepatocytes, although a late test of viability, suggest that both control and septic livers remained viable during perfusion. The results are consistent with the concept that different hepatocellular functions are individually regulated during sepsis. Thus, impairment of certain hepatocellular functions does not necessarily imply generalized liver failure.
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PMID:Individual regulation of different hepatocellular functions during sepsis. 151 25

A two-stage radioactive antiglobulin test--using unlabelled antisera specific for IgG, IgA, IgM and C3 followed by binding of 125I-staphylococcal protein A--was applied to determine platelet-associated immunoglobulins (PAIg) and complement (PAC3) in thrombocytopenias of various etiologies. One hundred and one patients with immune thrombocytopenia (chronic autoimmune, 48; acute autoimmune, 37; Evans syndrome, nine; connective tissue diseases, seven) and 20 patients with presumed nonimmune thrombocytopenia (bone marrow aplasia or malignancy, six; septicemia, five; hypersplenism, five; cirrhosis of liver, three; others, one) were studied. Increased levels of PAIg/C3 were found in 76% of patients with immune thrombocytopenia. PAIgG was raised in 66%, PAIgM in 57%, PAIgA in 44%, and PAC3 in 29%. Isolated elevation of PAIgG and of PAIgM was found in four and three cases, respectively; PAIgA and PAC3 were elevated in one case each. PAIgG was associated with PAIgM in 56%, with PAIgA in 34%, and with PAC3 in 27%. Both patients with Evans' syndrome and patients with connective tissue diseases had significantly higher PAIgM levels than the other patients with immune thrombocytopenia. In patients with nonimmune thrombocytopenia, increased rates of PAIg/C3 were also encountered. Positive test results were found in 88% (PAIgG 88%, PAIgM 47%, PAIgA 35%, and PAC3 24%). In immune-mediated thrombocytopenia, we observed a significant inverse correlation between platelet counts and PAIgG, PAIgA, and PAC3, but not with PAIgM. In contrast, no such correlation was found in patients with nonimmune thrombocytopenia. Our data indicate that the evaluation of neither parameter alone nor the combination of PAIg/C3 will discriminate between immune and nonimmune thrombocytopenia. Preferential coating with certain immunoglobulins, however, may be present in some subgroups of immune thrombocytopenias.
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PMID:Platelet-associated immunoglobulins IgG, IgM, IgA and complement C3 in immune and nonimmune thrombocytopenic disorders. 375 69

Eleven patients (10 boys, one girl) with Evans' syndrome with a median follow up time of 8.0 years were evaluated retrospectively. Six patients had either persistent hepatosplenomegaly or generalised lymphadenopathy, or both. In five patients, an increase in lymph node and/or spleen size was observed during the exacerbations of cytopenias. Seven patients had quantitative serum immunoglobulin abnormalities at the time of presentation. There were associated systemic manifestations in nine patients. Various forms of treatment were used with mixed results. Four patients died from sepsis and haemorrhage; four had complete recovery--two after splenectomy. These findings show that Evans' syndrome is a heterogeneous disorder with significant morbidity and mortality. High incidence of quantitative serum immunoglobulin abnormalities, lymphoid hyperplasia, and associated systemic manifestations suggest that Evans' syndrome may represent a stage of a more broad spectrum, generalised immune dysregulation.
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PMID:The spectrum of Evans' syndrome. 962 17

This study was designed to evaluate the decreased permselectivity of the capillary wall and the resultant higher permeability to macromolecular anionic albumin in septic rats, by quantitative estimation of Evans blue-albumin complexes in interstitial tissue. Septic peritonitis was induced by intraperitoneal injection of Escherichia coli-O6 KS H16. Twenty-four hours after induction of septic peritonitis, intact (healthy, noninoculated animals) and septic rats were perfused with 5 mL/Kg of a solution of Evans blue in normal saline (20 mg/mL in .9% NaCl). In septic rats, the interstitial concentration of Evans blue in mesentery, pancreas, and diaphragmatic muscle was significantly higher than that observed in intact animals. The present observations were made in the same experimental model of abdominal sepsis that showed a substantial reduction in the endothelial negative charge of the mesenteric, pancreatic, and diaphragmatic capillary beds. The evidence obtained from this experiment confirms that the loss of the permselective properties of capillary wall for macromolecular anionic albumin derives from a drastic reduction of its normally present and regularly distributed fixed electronegative charges.
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PMID:Increased mesenteric, diaphragmatic, and pancreatic interstitial albumin content in rats with acute abdominal sepsis. 948 59

Group B streptococci (GBS) are the leading cause of pneumonia and sepsis in human newborns. Exudative pulmonary edema and alveolar hemorrhage seen in GBS pneumonia indicate vascular damage, and we reported that GBS injure lung microvascular endothelial cells (LMvEC) both in vivo and in vitro. The specific GBS factors causing LMvEC injury are uncertain, but GBS beta-hemolysin activity is associated with lung epithelial cell injury. We hypothesized that GBS beta-hemolysin contributes to LMvEC injury and exudative pulmonary edema. To test this hypothesis we used isogenic nonhemolytic and hyperhemolytic GBS mutants derived by transposon insertional mutagenesis from three different wild-type strains. Hemolytic titers for each strain were calculated using live GBS and Tween 80/starch-stabilized extracts of log-phase GBS. All nonhemolytic mutants lacked detectable hemolytic activity, whereas hyperhemolytic mutants produced 4-16 times the hemolytic activity of their parent strains. LMvEC injury was assayed by light microscopy, the release of lactate dehydrogenase, trypan blue nuclear staining and Evans blue-albumin flux. Compared with the parent strains, all nonhemolytic mutants caused significantly reduced, and all hyperhemolytic mutants caused significantly greater lactate dehydrogenase release from and trypan blue nuclear staining of LMvEC. Moreover, a nonhemolytic mutant caused reduced and a hyperhemolytic mutant caused increased Evans-blue albumin flux across polar LMvEC monolayers. These findings were corroborated by light microscopic evidence of hemolysin-associated damage to the LMvEC monolayers. We conclude that GBS beta-hemolysin promotes LMvEC injury and increases permeability in vitro, and speculate that GBS beta-hemolysin contributes to the pathogenesis of alveolar edema and hemorrhage in early onset GBS pneumonia.
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PMID:Group B streptococcal beta-hemolysin promotes injury of lung microvascular endothelial cells. 1023 55

Acute graft versus host disease (GVHD) occurred in a patient after cadaveric liver transplantation from an HLA disparate donor. Immunosuppression resulted in a remission, but chronic GVHD with a scleroderma-like syndrome ensued. This was further complicated by immune hemolytic anemia and thrombocytopenia (Evan's syndrome). Semi-quantitative microsatellite analysis of circulating lymphoid cells showed that T cells were predominantly of donor origin, thereby explaining the chronic GVHD. The marrow hematopoietic cells remained recipient, so that the immune cytopenias were expected to be alloimmune in nature. However, the red cell antibodies were shown to have anti-C and anti-e specificity, with both the donor (R1R1) and recipient (R1r) possessing the C and e antigens. Therefore, the immune hemolysis might be considered both alloimmune and autoimmune. The patient finally died of sepsis. This case illustrates that chronic GVHD due to stable donor T cell engraftment may rarely occur in liver transplantation despite HLA disparity. Immunosuppression may result in dysregulation of T cell functions, leading to alloimmune and autoimmune problems.
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PMID:Evans' syndrome complicating chronic graft versus host disease after cadaveric liver transplantation. 1150 87

The effects of nitric oxide (NO) from calcium-independent NO synthase (iNOS) on microvascular protein leak in acute lung injury (ALI) are uncertain, possibly because of disparate effects of iNOS-derived NO from different cells. We assessed the contribution of iNOS from inflammatory versus parenchymal cells to pulmonary protein leak in murine cecal ligation and perforation-induced ALI. We studied iNOS+/+, iNOS-/-, and two reciprocally bone marrow-transplanted iNOS chimeric mice groups: + to - (iNOS+/+ donor bone marrow-transplanted into iNOS-/- recipient mice) and - to +. Sepsis-induced ALI was characterized by pulmonary leukocyte infiltration, increased pulmonary iNOS activity, and increased pulmonary microvascular protein leak, as assessed by Evans blue (EB) dye. Despite equal neutrophil infiltration, sepsis-induced EB-protein leak was eliminated in iNOS-/- mice and in - to + iNOS chimeras (parenchymal cell-localized iNOS) but was preserved in + to - chimeric mice (inflammatory cell-localized iNOS). EB-protein leak was also prevented by pretreatment with allopurinol and superoxide dismutase. Microvascular protein leak in sepsis-induced ALI is uniquely dependent on iNOS in inflammatory cells with no obvious contribution of iNOS in pulmonary parenchymal cells. Pulmonary protein leak is also dependent on superoxide, suggesting an effect of peroxynitrite rather than NO itself.
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PMID:Role of inducible nitric oxide synthase in pulmonary microvascular protein leak in murine sepsis. 1207 65

Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial wall components. TLR2 function was investigated in a murine Streptococcus pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. TLR2(-/-) mice showed earlier time of death than wt mice (P<.02). Plasma interleukin-6 levels and bacterial numbers in blood and peripheral organs were similar for both strains. With ceftriaxone therapy, none of the wt but 27% of the TLR2(-/-) mice died (P<.04). Beyond 3 hours after infection, TLR2(-/-) mice had higher bacterial loads in brain than did wt mice, as assessed with luciferase-tagged S. pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera. After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of TLR2(-/-) than wt mice (P<.05) and was related to increased blood-brain barrier permeability (Evans blue staining, P<.02). In conclusion, the lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.
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PMID:Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation. 1219 14

Magnolol is a Chinese herb that has potent antioxidant effects. This study evaluated the effect of magnolol in the treatment of severe injury using a two-hit model in Sprague-Dawley rats. Hemorrhagic shock followed by resuscitation was performed. Intra-abdominal sepsis was induced by cecal ligation puncture. The rats were randomly segregated into the following three groups: group 1 (sham group) rats were sham-operated; group 2 (untreated group) rats received hemorrhagic shock and resuscitation and cecal ligation puncture 24 h later; and group 3 (treated group) rats were treated with magnolol and subjected to the same procedures as group 2. Plasma cytokine levels and tissue cytokine contents of lung, including tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-10 were assayed after hemorrhagic shock and sepsis. Pulmonary injury study was performed using Evans blue dye and survival analysis was performed after development of sepsis. Plasma and tissue TNFalpha levels increased after hemorrhagic shock. Magnolol treatment blunted the TNFalpha levels in plasma and tissue. The plasma IL-10 level increased after hemorrhagic shock, whereas the tissue level of IL-10 did not change. Magnolol treatment did not alter the plasma level of IL-10 but did increase tissue level. After sepsis, TNFalpha levels in both plasma and tissue of magnolol-treated animals were significantly lower than those in untreated animals, whereas plasma and tissue IL-10 levels were not significantly different between treated and untreated groups. Pulmonary injury study showed that magnolol-treated rats had decreased pulmonary permeability after the onset of sepsis. Survival analysis showed that survival rate was significantly higher in the treated group. In conclusion, magnolol modifies the cytokine response after hemorrhagic shock and resuscitation; the proinflammatory cytokine response is suppressed. The modified cytokines response induced by magnolol may result in decreased tissue injury and increased survival in subsequent intra-abdominal sepsis.
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PMID:Magnolol alters cytokine response after hemorrhagic shock and increases survival in subsequent intraabdominal sepsis in rats. 1292 99


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