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)

Administration of intravenous polyspecific immunoglobulin G (IVIG) has been proposed as adjunctive therapy for toxic shock syndrome caused by Streptococcus pyogenes or Staphylococcus aureus. We investigated whether superantigen-containing culture supernatants prepared from streptococcal isolates (n=21) and staphylococcal isolates (n=20) from cases of severe sepsis were inhibited to an equal extent by IVIG in proliferation experiments that used human peripheral blood mononuclear cells. All 3 IVIG preparations tested were highly efficient in neutralizing the superantigens, and most supernatants were completely inhibited at concentrations ranging from 0.05 to 2.5 mg IVIG/mL. An important finding was that culture supernatants from S. pyogenes isolates were consistently inhibited to a greater extent than those of S. aureus isolates (P<.01). The findings demonstrate that staphylococcal superantigens are not inhibited as efficiently as streptococcal superantigens by IVIG, and, hence, a higher dose of IVIG may be required for therapy of staphylococcal toxic shock syndrome in order to achieve protective titers and clinical efficacy.
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PMID:Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications for therapy of toxic shock syndrome. 1499 28

While moderate hypothermia is protective against ischemic cardiac and brain injury, it is associated with much higher mortality in patients with sepsis. We previously showed that in vitro exposure to moderate hypothermia (32 degrees C) delays the induction and prolongs the duration of TNF-alpha and IL-1beta secretion by lipopolysaccharide (LPS)-stimulated human mononuclear phagocytes. In the present study, we extended these observations by showing that moderate hypothermia exerts effects on TNF-alpha and IL-1beta generation in the human THP-1 monocyte cell line that are similar to those that we previously found in primary cultured monocytes; that hypothermia causes comparable changes in cytokine generation stimulated by zymosan, toxic shock syndrome toxin-1, and LPS; and that hypothermia causes similar changes in TNF-alpha and IL-1beta mRNA accumulation. TNF-alpha mRNA half-life, determined after transcriptional arrest with actinomycin D, was not significantly prolonged by lowering incubation temperature from 37 to 32 degrees C, suggesting that hypothermia modifies TNF-alpha gene transcription. This finding was further supported by reporter gene studies showing a threefold increase in activity of the human TNF-alpha promoter at 32 vs. 37 degrees C. Electrophoretic mobility shift assay revealed that hypothermia prolonged NF-kappaBeta activation, identifying a potential role for this transcription factor in mediating the effects of hypothermia on TNF-alpha and IL-1beta production. Delayed reexpression of the inhibitor IkappaBalpha, shown by Northern blotting and immunoblotting, may account in part for the prolonged NF-kappaBeta activation at 32 degrees C. Augmentation of NF-kappaBeta-dependent gene expression during prolonged exposure to hypothermia may be a common mechanism leading to increased lethality in sepsis, late-onset systemic inflammatory response syndrome after accidental hypothermia, and neuroprotection after ischemia.
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PMID:Hypothermia prolongs activation of NF-kappaB and augments generation of inflammatory cytokines. 1507 Aug 15

A prospective, nationwide, laboratory-based surveillance of invasive group A streptococcal infections was conducted in the Netherlands from 1992 through 1996. Clinical and demographic data were obtained and all isolates were T/M typed. All noninvasive group A streptococcal isolates were registered from 1994 through 1996. A total of 880 patients with invasive streptococcal disease were identified. The annual incidence was found to be 2.2 per 100,000. Predominant M types were M1 (21%), M3 (11%), M6 (5%), M12 (5%), and M28 (8%). Particular age and M-type distributions were observed in different clinical entities. The case-fatality rate was 18% overall, but it reached 59% among cases of toxic shock-like syndrome. Older age, necrotizing fasciitis, sepsis without focus, pneumonia, infection with type M1 or M3 strains, and underlying cardiopulmonary disease were associated with fatality. A total of 10,105 patients with noninvasive group A streptococcal disease were registered. These patients differed significantly from patients with invasive disease with regard to age distribution and primary foci of infection.
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PMID:Epidemiological features of invasive and noninvasive group A streptococcal disease in the Netherlands, 1992-1996. 1516 57

In Staphylococcus aureus, 19 different superantigens (SAgs) have been described. Their genes are all located on mobile genetic elements, such as pathogenicity islands, plasmids, and phages. SAgs bypass conventional antigen recognition by directly cross-linking major histocompatibility complex class II (MHCII) molecules on antigen-presenting cells with T cell receptors. This leads to massive T cell proliferation and cytokine release, which may end in toxic shock syndrome. The role of SAgs in other forms of sepsis is less well defined. In animal models, SAgs and lipopolysaccharide (LPS) very efficiently synergize in the induction of lethal shock, and on the basis of these observations a two-hit model of sepsis has been proposed: LPS or another monocyte stimulus hits first, then SAg or another T cell stimulus hits. In clinical studies, however, evidence for an involvement of SAgs in sepsis has been difficult to obtain. This may have a number of reasons: differences between humans and rodents in their response to LPS and SAg, heterogeneity of SAg combinations in S.aureus clinical isolates, lack of tools to analyze SAg effects in patients, blocking anti-SAg serum antibodies, and MHCII polymorphisms.
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PMID:Staphylococcal superantigens: do they play a role in sepsis? 1576 73

Clinical efficacy of polyspecific immunoglobulins or monoclonal antibodies to treat patients with severe sepsis or septic shock is still under debate after several clinical trials. Only a few of them have been able to demonstrate a direct benefit to reduce mortality or this effect appears after meta-analysis. Evidence sustains that polyspecific immunoglobulin G reduces mortality in these patients, being this effect higher for IgM-enriched immunoglobulins. Best indications are postsurgical sepsis or early septic shock patients with high titers of endotoxinemia. The use of intravenous immunoglobulins is also recommended for the treatment of patients with streptococcal toxic shock, as demonstrated by the evidence obtained through case-control studies and one randomized clinical trial with a clear trend toward benefit. Evidence does not sustain a favorable impact on mortality for monoclonal antibodies directed against bacterial lypopolysaccaride, other bacterial antigens or against TNF-alpha. Furthermore, infusion of recombinant IL-1 receptor antagonist or soluble receptors for TNF-alpha that could attenuate the inflammatory response have not demonstrated utility after many clinical trials. These therapeutic tools are characterized by a high acquisition cost and adequate cost-effectiveness analysis has not been yet performed.
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PMID:[Immunoglobulins in sepsis and septic shock]. 1579 66

Serotype VI group B Streptococcus (GBS) has been almost frequently isolated among colonizing strains of pregnant women in Japan, but the clinical features and prognosis, when a patient is invasively infected, are largely unknown. We report, for the first time, three cases of fatal infection caused by serotype VI GBS; two cases were middle-aged men with necrotizing fasciitis/cellulitis, sepsis, and toxic shock syndrome with poorly controlled diabetes as underlying conditions; and one was a premature infant with intrauterine infection. Our results indicated that type VI GBS is pathogenic for humans not only in fetuses but also adults, and has the ability to be fatal, at least in selected patients.
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PMID:Three fatal cases of invasive serotype VI group B streptococcal infection. 1640 80

The mortality from septic shock remains high despite the availability of modern critical care facilities. In recent years, new agents have been tested to reduce morbidity and mortality in patients with severe sepsis. Among them, recombinant human activated protein C (rhAPC) has been reported to significantly reduce mortality and morbidity in patients with severe sepsis and one or more acute organ failures. We describe our experience with this drug in the early reversal of septic shock from toxic shock syndrome.
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PMID:Activated protein C in toxic shock syndrome: a case report. 1657 75

From mid-July to the end of August 2005, a total of 215 cases of human Streptococcus suis infections, 66 of which were laboratory confirmed, were reported in Sichuan, China. All infections occurred in backyard farmers who were directly exposed to infection during the slaughtering process of pigs that had died of unknown causes or been killed for food because they were ill. Sixty-one (28%) of the farmers had streptococcal toxic shock syndrome; 38 (62%) of them died. The other illnesses reported were sepsis (24%) and meningitis (48%) or both. All isolates tested positive for genes for tuf, species-specific 16S rRNA, cps2J, mrp, ef, and sly. A single strain of S. suis caused the outbreak, as shown by the identification of a single ribotype. The high death ratio was of concern; prohibiting backyard slaughtering ended the outbreak.
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PMID:Human Streptococcus suis outbreak, Sichuan, China. 1670 46

Among 28 patients with necrotizing fasciitis 18 patients had the syndrome of infectious-toxic shock with clinically severe manifestations. Nine of them had the disease with most serious (lightening-like) clinical forms of severe sepsis that led to lethal outcomes within 1-3 days. This form is referred to as an irreversible septic shock and genetically is due to two factors: 1. Type of the pathogen (Streptococcus pyogenes) whose toxin is responsible for the septic shock syndrome. 2. Spacious zone of the superficial fascia necrosis, a massive source of endotoxemia resulting from generalized thrombosis of the microcirculation bed of the fascial structures. There is no alternative to the method of treatment of patients with necrotizing fasciitis but urgent (immediately after the diagnosis) and aggressive in volume and character operation as well as an adequate resuscitation management and antibiotic therapy.
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PMID:[Syndrome of infectious-toxic shock in the structure of patients with necrotizing fasciitis]. 1688 Nov 89

Group A Streptococcus pyogenes causes a distinctive clinical disorder, streptococcal toxic shock syndrome, mediated by superantigenic bacterial exotoxins. Oncology patients with viridans group streptococcal sepsis frequently present with a streptococcal toxic shocklike syndrome of unclear pathogenesis. Viridans group streptococci isolated from pediatric oncology patients with streptococcal toxic shocklike illnesses do not possess homologs of known superantigen genes. Supernatants from cultures of these bacteria also fail to stimulate T-cell proliferation, suggesting these bacteria do not commonly elaborate superantigens. Adjunctive treatment with intravenous immunoglobulin, which is advantageous in streptococcal toxic shock syndrome, may not benefit these patients.
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PMID:Failure of viridans group streptococci causing bacteremia in pediatric oncology patients to express superantigens. 1700 72


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