Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Septic adrenal hemorrhage is classically caused by meningococcemia. An autopsied case is presented of a 45-year-old man with adrenal hemorrhage due to Klebsiella oxytoca bacteremia following placement of a central venous catheter. He died 5 hours after developing disseminated intravascular coagulation (DIC). The bacterial entry site may have been the catheter. The cause of death was considered to be pulmonary edema due to bacteremia rather than adrenal insufficiency due to hemorrhage. Septic adrenal hemorrhage should be recognized as a subtype of sepsis rather than adrenal insufficiency, and may be caused in conditions of severe sepsis with DIC, independent of the microorganic variety.
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PMID:Adrenal hemorrhage associated with Klebsiella oxytoca bacteremia. 986 68

Activated protein C (APC) is a natural anticoagulant that plays a pivotal role in coagulation homeostasis. Severe inherited or acquired deficiency results in a clinical syndrome called purpura fulminans. In addition, APC also appears to have potent cytokine-modifying properties and is protective in animal models of sepsis. The dual functional properties of APC are particularly relevant to severe meningococcemia, where acquired PC deficiency is accompanied by multiorgan failure and purpura fulminans. The authors conducted an open-label prospective study assessing the efficacy of PC replacement therapy in patients with severe meningococcal septicemia, purpura fulminans, and multiorgan failure. The morbidity and mortality were compared with predicted morbidity using the Glasgow Meningococcal Septicemia Prognostic Score. Thirty-six patients with a mean age of 12 years (range 3 months to 72 years) were enrolled in the study. The mean +/- SD for plasma PC was 18 +/- 7 IU/mL. PC was significantly lower than antithrombin or protein S and was also significantly lower than PC levels in a cohort of patients who developed meningococcemia without multiorgan failure and purpura fulminans. A total of 3 of 36 (8%) patients died, which compares favorably with predicted mortality of 18 of 36 (50%). Amputations were required in 4 of 33 (12%) survivors and in 2 of 31 (6.5%) patients who received PC within 24 hours of admission into the hospital, in comparison with the predicted amputation rate of 11 of 33 (30%). In conclusion, PC replacement therapy in severe meningococcal septicemia was associated with a reduction in predicted morbidity and mortality. The beneficial effect of PC replacement may reflect both the anticoagulant and anti-inflammatory properties of the PC pathway. (Blood. 2000;96:3719-3724)
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PMID:An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans-associated meningococcemia. 1109 52

Severe meningococcemia, which is associated with hemodynamic instability, purpura fulminans and disseminated intravascular coagulation, still has a high mortality rate, and patients who survive are often left invalids because of amputations and organ failure. Clinical studies have shown that levels of protein C are markedly decreased in patients with severe meningococcemia and that the extent of the decrease correlates with a negative clinical outcome. There is a growing body of data demonstrating that activated protein C, in addition to being an anticoagulant, is also a physiologically relevant modulator of the inflammatory response. The dual function of protein C may be relevant to the treatment of individuals with severe meningococcal sepsis. In the present review we give a basic overview of the protein C pathway and its anticoagulant activity, and we summarize experimental data showing that activated protein C replacement therapy clearly reduces the mortality rate for fulminant meningococcemia.
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PMID:Protein C replacement in severe meningococcemia: rationale and clinical experience. 1130 70

During the past 15 years, several anti-inflammatory treatments have failed to reduce mortality in patients with severe sepsis. However, recent evidence indicates that coagulation abnormalities in sepsis may play a major role in the pathogenesis of multiple organ failure and the high mortality rate in patients with severe sepsis. Interestingly, blockade of the coagulant pathway can inhibit both procoagulant and proinflammatory pathways in sepsis. Protein C, a natural anticoagulant, interrupts several of the pathophysiologic pathways in sepsis. Acquired protein C deficiency is present in the majority of septic patients and is associated with unfavorable outcomes. Protein C replacement therapy was effective in preclinical animal models of sepsis in reducing end-organ damage and mortality. Recent clinical trials of protein C replacement in human meningococcemia resulted in a markedly decreased morbidity and mortality. And, most importantly, in a recently completed large, randomized trial of activated protein C treatment in severe sepsis, mortality was reduced from 30.8% in the placebo group to 24.7% in the treatment group at 28 days. Thus, there is new evidence that mortality can be reduced among patients with severe sepsis through the use of a new therapy that inhibits the procoagulant and the inflammatory cascades.
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PMID:The Role of Protein C in Sepsis. 1155 61

A 22-y-old male developed fever, arthralgias and skin rash 2 d after tonsillectomy. Blood culture grew Neisseria meningitidis. He responded well to antibiotics. Only 1 other case of meningococcal sepsis following adenotonsillectomy has previously been reported. These cases suggest a temporal association of meningococcemia with tonsillectomy.
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PMID:Meningococcemia following tonsillectomy. 1186 68

Neisseria meningitidis (meningococcus), an exclusive pathogen of humans, is the cause of sepsis (meningococcemia) and meningitis, often in otherwise healthy individuals. Several hundred thousand cases of meningococcal disease occur worldwide each year, a number that is frequently accentuated by epidemic outbreaks. In recent years, significant advances, fueled by new molecular approaches and genome sequencing projects, have improved our understanding of the pathogenesis of meningococcal disease and have led to progress in the development of the next generation of meningococcal vaccines. However, the mortality of meningococcal disease remains 10% to 15% for all cases, and is up to 40% in patients with severe sepsis. This review summarizes current knowledge of the pathogenesis, therapy, and prevention of meningococcal disease with emphasis on meningococcal sepsis.
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PMID:Pathogenesis, Therapy, and Prevention of Meningococcal Sepsis. 1222 24

We developed a model of sequential influenza A virus (IAV)-Neisseria meningitidis serogroup C (Nm) infection in BALB/c mice. Mice infected intranasally with a sublethal IAV dose (260 pfu) were superinfected intranasally with Nm. Fatal meningococcal pneumonia and bacteremia were observed in IAV-infected mice superinfected with Nm on day 7, but not in those superinfected on day 10. The susceptibility of mice to Nm superinfection was correlated with the peak interferon-gamma production in the lungs and decrease in IAV load. After Nm challenge, both IAV-infected and uninfected control mice produced the inflammatory cytokines interleukin (IL)-1 and IL-6. However, IL-10 was detected in susceptible mice superinfected on day 7 after IAV infection, but not in resistant mice. This model of dual IAV-Nm infection was also used to evaluate the role of bacterial virulence factors in the synthesis of the capsule. A capsule-defective mutant was cleared from the lungs, whereas a mutant inactivated for the crgA gene, negatively regulating expression of the pili and capsule, upon contact with host cells, retained invasiveness. Therefore, this model of meningococcal disease in adult mice reproduces the pathogenesis of human meningococcemia with fatal sepsis, and is useful for analyzing known or new genes identified in genomic studies.
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PMID:A model of meningococcal bacteremia after respiratory superinfection in influenza A virus-infected mice. 1275 52

Acute renal failure is a common occurrence in sepsis, but is rarely reported in meningococcemia. We present a young child diagnosed with fulminant meningococcemia who had several poor prognostic factors, including hypotension, thrombocytopenia, purpura fulminans, seizures, the absence of meningitis with meningococcemia, and acute renal failure, which was successfully treated with peritoneal dialysis. Peritoneal dialysis was started on the 5th day because the patient had been anuric for 48 h. At that time, analysis showed that the child was both hypokalemic and hypophosphatemic. His serum blood urea nitrogen was 61 mg/dl, creatinine 2.75 mg/dl, potassium 2.8 mEq/l, and phosphorus 0.7 mg/dl. Urine output began on the 12th day post admission and normalization of serum creatinine was achieved on the 26th day. In conclusion, renal failure is an important complication of meningococcemia and, to be effective, sometimes long-term peritoneal dialysis is required. Profound metabolic abnormalities, such as hypokalemia and hypophosphatemia, may occur paradoxically in the presence of oliguria.
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PMID:Fulminant meningococcemia and acute renal failure in a 3-year-old boy. 1549 Feb 48

Recent studies have shown that genetic variants, responsible for the different human response when facing an infectious risk, concerned the genes of proteins involved in either recognition of the infectious agent, in the inflammatory cascade, or in the coagulation process. For example, some studies clearly demonstrated that if a twin was affected by an infectious disease, the risk of infection by the same agent for the other twin was significantly higher in homozygote than in heterozygote twins. In Caucasians, a punctual mutation of the TLR2 cytosol was proved to block the response to bacterial lipoproteins and to some Gram positive bacteria and could be responsible for a greater susceptibility to septic shock. Several polymorphisms of the tlr4 gene have been involved in the onset of septic shock in postsurgery infection due to Gram(-) bacilli. Paradoxically, these variants seemed to protect against legionellosis. In pediatrics, polymorphisms of tlr4 were also clearly identified as risk factors for meningococcemia of severe bronchiolitis due to the respiratory syncytial virus (RSV) in children under 2 years of age. A polymorphism of the TLR5 receptor gene, which creates a stop codon and which is responsible for a nonfunctionality of the receptor was associated with the onset of severe legionellosis. Analysing the functions of these genetic polymorphisms in the onset of sepsis will open the way to a lot of research on specific treatments focused on genetic abnormalities.
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PMID:[Genetic polymorphisms and infections]. 1669 44

Neisseria meningitidis causes acute severe diseases, including sepsis and meningitis, and more benign manifestations such as chronic meningococcemia or colonization of the upper respiratory tract. The inflammatory response, which contributes to the pathogenesis of meningococcal disease, is initiated by pattern recognition receptors, among which Toll-like receptors (TLR)s have been ascribed a particularly important role. We have previously demonstrated that N. meningitidis induce proinflammatory cytokine expression through TLR2 and TLR4. Here we characterize the molecular basis for differential activation of the inflammatory response by two N. meningitidis strains. This difference was due to differential ability to activate signal transduction through TLR4, as HEK293 cells expressing TLR4 produced significantly different levels of interleukin-8 in response to these strains. At the level of signal transduction, the two strains differed substantially in their ability to activate the pathway to nuclear factor kappaB in HEK293-TLR4/MD2 cells at late, but not early, time points. TLR4 activates two signal transduction pathways: one dependent on the adaptor molecule MyD88 and one independent of MyD88, and these pathways induce distinct patterns of gene expression in response to TLR4 ligands. By using macrophages from TLR2-/- mice, we observed that the two strains differed in their ability to activate the TLR4-induced MyD88-independent pathway, but not the MyD88-dependent pathway. This idea was further supported by experiments where either of the two pathways was inhibited and IL-8 secretion was measured. These data therefore provide molecular insight into activation of the inflammatory response by N. meningitidis, which is one of the key events in the pathogenesis of meningococcal disease.
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PMID:Two neisseria meningitidis strains with different ability to stimulate toll-like receptor 4 through the MyD88-independent pathway. 1708 21


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