Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical presentation of infections caused by Neisseria meningitidis is highly diverse. Some patients develop meningitis, and others present with sepsis or even septic shock. After invasion of the bloodstream by the bacteria, three main cascade pathways are activated. These are the complement system, the inflammatory response, and the coagulation and fibrinolysis pathway. These pathways do not act independently but are able to interact with each other. Genetic polymorphisms among components of these pathways have been shown to be involved in the susceptibility, severity, and outcome of meningococcal disease. We review knowledge of genetic variations associated with susceptibility to and severity of meningococcal infection. Complement deficiencies and defects in sensing or opsonophagocytic pathways, such as the rare Toll-like receptor 4 single nucleotide polymorphisms (SNPs) and combinations of inefficient variants of Fcgamma-receptors, seem to have the most important role in genetically established susceptibility. Effect on severity has repeatedly been reported for FcgammaRIIa and plasminogen activator inhibitor type 1 (PAI1) polymorphisms. Outcome effects have been confirmed for SNPs in properdin deficiencies, PAI1 and combination of the -511C/T SNP in interleukin 1beta, and the +2018C/T SNP in interleukin RN. Conflicting results are reported for the effect of the -308G/A promoter polymorphism in tumour necrosis factor (TNF) alpha. These differences may reflect discrepancies in group definitions between studies or the influence of additional SNPs in the TNFalpha promoter, which can form haplotypes representing different cytokine production capacity. For several SNPs, the potential effect on susceptibility, severity, or outcome has not yet been confirmed in an independent study.
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PMID:Host genetic determinants of Neisseria meningitidis infections. 1295 63

Waterhouse-Friderichsen syndrome--massive adrenal haemorrhage in the setting of overwhelming clinical sepsis--is usually taken at necropsy to indicate meningococcal infection, and may be the only evidence of this pathogen. This report describes three fatal cases of the syndrome in which the causative organism proved to be a streptococcus. The organisms were detected during routine coroners' autopsies with histology and microbiological investigations. In two cases, the syndrome followed Streptococcus pneumoniae infection and in a third beta haemolytic streptococcus group A. Thus, adrenal haemorrhage alone cannot be taken to indicate meningococcal disease and other pathogens, particularly streptococcus, must be considered.
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PMID:Waterhouse-Friderichsen syndrome as a result of non-meningococcal infection. 1474 54

Despite advances in critical care medicine, acute meningococcal infection remains complicated by high mortality. Different prognostic scoring systems have been developed but none of them is largely used. The objective of this study was to evaluate the performance at admission to the pediatric intensive care unit (PICU) of five severity scores in children with proven and unproven meningococcal infection. Our results seem to indicate that the Neisseria Sepsis Index (NESI) and the Rotterdam Score (RS) perform better than the other scores, being appropriate tools to assess severity of illness at admission to the PICU in children with proven or presumed meningococcal infection.
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PMID:[Assessment of severity of meningococcal sepsis in children]. 1475 Feb 74

Individuals vary considerably in their susceptibility to infection and in their ability to recover from apparently similar infectious processes. These differences can be partially explained by polymorphisms of the genes encoding proteins involved in mediating and controlling the innate immune response, the inflammatory cascade, coagulation, and fibrinolysis. It is evident from experimental studies that dysregulation of the coagulation system, which is characteristic of the pathophysiology of septic shock (a procoagulant and antifibrinolytic state), contributes to systemic inflammation and death in sepsis. Several genetic variations in proteins that increase coagulation or impair anticoagulation and fibrinolysis have been described. Thus, polymorphisms have been reported in prothrombin, fibrinogen, factor V, tissue factor, endothelial protein C receptor, and plasminogen activator inhibitor-1 genes. Some of them are associated with an increased risk of pulmonary emboli, acute myocardial infarction, stroke, and severe sepsis. Hence, the deletion polymorphism (4G) within the promoter region of the plasminogen activator inhibitor-1 gene leads to impaired fibrinolysis and influences the severity and outcome of meningococcal disease and the susceptibility to severe sepsis and multiple organ failure after trauma. The factor V Leiden mutation is associated with thrombotic events and has been reported to exacerbate purpura fulminans in meningococcal infection. Surprisingly, this genetic variant seems to provide a survival advantage in severe sepsis, underlying the extreme complexity of the interaction between inflammation and coagulation. The study of genetic polymorphisms might provide important insights into the pathogenesis of severe sepsis and could make it possible to identify individuals who are at risk of developing or dying of severe infections. As genetic associations are discovered, medical practice can become more preemptive, using the predictive ability of genetics to anticipate disease and recommend therapy.
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PMID:Importance of hemostatic gene polymorphisms for susceptibility to and outcome of severe sepsis. 1511 37

The authors report on the method, course and results of treatment of patients with meningococcal septicaemia. The two most common forms of meningococcal disease are meningococcal septicaemia (MS) and meningitis. Severe MS is a fulminant form of sepsis characterized by a rapidly spreading purpuric rash, haemodynamic instability and rapid progression to shock or death. The diganosis of MS was confirmed by isolation of NM in blood or cerebrospinal fluid, and/or positive solubile bacterial antigenes. However, in some children whose symptoms were consistent in MS (temperature and extensive purpura), no bacterial or soluble antigens were detected, particularly when they had been previours antibiotic treatment. Several scoring systems have been used to predict morbidity and mortility from MS. We selected the prognostic scor developed by Malley et al. Absolute neutrophil count less than 3 x 10(3)/mm3, platelet count less than 150 x 10(3)/mm3 and poor perfusion are indicators of poor prognosis. The presence of at least two of these indicators was associated with an 82% of risk of death. We reviewed the hospital records of 36 paediatric patients with acute meningococcal infection during a 5-year period. The age of our patients ranged from 2 months to 15 years (mean 4.4 yrs). Twenty seven (70%) of 36 children had MS and 11 (40.7%) had both MS and meningitis. Based on Malley scor, 13 (48.1%) patients had at least two predictors with > 82% of risk of lethal outcome. Four children (30.7%) died. Severe MS was diagnosed in 16 (59.2%) patients, who required mechanical ventilation (16; 59.2%), or continuous inotropic support and invasive measures of circulatory parametars (15; 55.5%). Shock treatment consisted of large volumes of crystalloid or colloid infusions thad ranged from 140 to 500 ml/kg/24 hrs (mean 215 ml/kg) Our results indicate that early controlled mechanical ventilations increase safety of large volume infusion with continuous invasive monitoring and inotropic stimulation, and may contribute to a greater survival of children with severe MS.
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PMID:[Results of intensive therapy of meningococcal sepsis in children]. 1563 90

Chemokines are important in regulating leukocyte traffic during infection. We analyzed plasma chemokine levels of monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha , interleukin (IL)-8, and RANTES in patients with meningococcal infection and correlated these to plasma lipopolysaccharide (LPS) levels, which are closely associated with clinical presentation. In patients with fulminant meningococcal septicemia, versus distinct meningitis or mild systemic meningococcal disease, MCP-1 (both P<.0001), MIP-1 alpha (both P<.0001), and IL-8 (P<.0001 and P=.011) were significantly higher and RANTES significantly lower (P=.007 and P=.021). MCP-1 (r=.88), MIP-1 alpha (r=.82), and IL-8 (r=.89) were positively correlated to plasma LPS levels, whereas RANTES was negatively correlated (r=-.49). In an ex vivo whole-blood model, heat-inactivated wild-type Neisseria meningitidis, purified meningococcal LPS, and (to a negligible extent) heat-inactivated LPS-deficient mutant N. meningitidis induced these chemokines. N. meningitidis LPS is the major cause of chemokine release in meningococcal disease.
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PMID:Chemokine patterns in meningococcal disease. 1568 94

Severe infections caused by Neisseria meningitidis, clinically appearing as meningitis or sepsis, are constantly noted in developed countries, including Poland. Because of rapid clinical course and mortality rate they continue to pose a serious clinical problem. Most cases are sporadic ones, caused by the contact with a healthy carrier of N. meningitidis. Familial and group outbreaks are rare, being responsible for about 1% of cases. However, in family members of patients with meningococcal infection the risk of developing the disease during the following week is about one hundred times higher than in the general population and they should receive an antibiotic prophylaxis. We describe a familial outbreak of meningococcal meningitis with typical clinical features, which appeared in two members of a family during the same day, with a case of acute pharyngitis most likely of the same etiology in the third person, a child. In that instance, practically simultaneous appearance of consecutive cases gave no time for prophylaxis. However, suspicion of meningococcal disease in the first patient contributed to the prompt hospitalization and diagnostics and proper treatment in the two following cases.
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PMID:[Meningococcal meningitis--familial outbreak]. 1575 42

Neisseria meningitidis (meningococcus) is an important cause of meningitis and sepsis. Currently, there is no effective vaccine against serogroup B meningococcal infection. Host defense against neisseriae requires the complement system (C) as indicated by the fact that individuals deficient in properdin or late C components (C6-9) have an increased susceptibility to recurrent neisserial infections. Because the classical pathway (CP) is required to initiate efficient complement activation on neisseriae, meningococci should be able to evade it to cause disease. To test this hypothesis, we studied the interactions of meningococci with the major CP inhibitor C4b-binding protein (C4bp). We tested C4bp binding to wild-type group B meningococcus strain (H44/76) and to 11 isogenic mutants thereof that differed in capsule expression, lipo-oligosaccharide sialylation, and/or expression of either porin (Por) A or PorB3. All strains expressing PorA bound radiolabeled C4bp, whereas the strains lacking PorA bound significantly less C4bp. Increased binding was observed under hypotonic conditions. Deleting PorB3 did not influence C4bp binding, but the presence of polysialic acid capsule reduced C4bp binding by 50%. Bound C4bp remained functionally active in that it promoted the inactivation of C4b by factor I. PorA-expressing strains were also more resistant to C lysis than PorA-negative strains in a serum bactericidal assay. Binding of C4bp thus helps Neisseria meningitidis to escape CP complement activation.
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PMID:Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis. 1587 29

Neisseria meningitidis is a major cause of sepsis and/or meningitis. These bacteria normally cause disease only in humans, however, mice expressing human CD46 are susceptible to meningococcal disease. To explain the sensitivity of CD46 transgenic mice to meningococci, we evaluated early immune responses. Stimulation of TNF, IL-6, and IL-10 was stronger in CD46 transgenic mice compared with nontransgenic mice, and resembled human responses. In CD46 transgenic mice, bacterial clearance in blood started at later time points, and neutrophil numbers in blood were lower compared with nontransgenic mice. Further, elevated levels of activated microglia cells and cyclooxygenase-2 were observed in brain of infected CD46 transgenic mice. Intraperitoneal administration of meningococci lead to increased levels of macrophages only in the i.p. cavity of CD46 transgenic mice. Most of the responses were impaired or absent using LPS-deficient meningococci, showing the importance of LPS in the early immune response to meningococcal infection. Taken together, these data demonstrate that responses in mice expressing human CD46 mimic human meningococcal disease in many aspects, and demonstrate novel important links between CD46 and the innate immune system.
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PMID:Human-like immune responses in CD46 transgenic mice. 1597 77

Plasminogen activator inhibitor type 1 (PAI-1) is a 50-kilodalton glycoprotein of the serine protease inhibitor family. The primary role of PAI-1 in vivo is the inhibition of both tissue- and urokinase-type plasminogen activators. In addition to this function, PAI-1 acts as an acute-phase protein during acute inflammation. PAI-1 is a pivotal player in the pathogenesis of sepsis, a complex clinical syndrome that results from a systemic inflammatory response. In patients with sepsis, the levels of PAI-1 are positively related to poor outcome, increased severity of disease, and increased levels of various cytokines, acute-phase proteins, and coagulation parameters. The 4G/5G insertion/deletion promoter polymorphism, which leads to differences in PAI-1 production, has been demonstrated to affect the risk of developing severe complications and dying from sepsis during meningococcal infection and multiple trauma.
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PMID:Plasminogen activator inhibitor type 1 gene polymorphism and sepsis. 1623 47


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