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

Levels of antibody to serotype VIII group B Streptococcus (GBS) were surveyed in serum samples from 583 pregnant women, from 461 neonates born to these women, and from 4 mother-and-neonate pairs with early-onset serotype VIII sepsis. Colonization by serotype VIII GBS was associated with significantly higher serum concentrations of serotype-specific antibodies (geometric mean [GM], 5.53 micro g/mL), compared with both noncolonization (1.53 micro g/mL) and colonization with other serotypes (2.19 micro g/mL). There was excellent correlation between antibody levels in mothers and those in their neonates. The prevalence of positive antibody levels, when arbitrarily defined, according to antibody levels in neonatal sepsis (GM, 0.49 micro g/mL) as >1.0 micro g/mL, was 58% of all pregnant women and 85% of the women colonized by serotype VIII. This high serotype prevalence may explain, at least in part, why serotype VIII causes early-onset neonatal disease at rates lower than those which would be expected on the basis of its prevalence in mothers in Japan who are colonized by GBS.
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PMID:Seroepidemiologic studies of serotype VIII group B Streptococcus in Japan. 1219 24

Historically, the leading cause of death among persons with haemophilia and other congenital coagulation disorders was uncontrolled bleeding. Mortality was associated with severe deficiency of coagulation factors VIII or IX and especially with high-titre antifactor neutralizing antibodies (inhibitors). The catastrophic contamination of plasma donor pools with human immunodeficiency virus (HIV) resulted in acquired immunodeficiency syndrome replacing haemorrhage as the leading cause of death among persons with haemophilia. Rather little has been written, however, about mortality among those not infected with HIV. The objective of this study was to identify conditions associated with all-cause mortality among HIV-uninfected patients who were followed for a mean of 8.8 years in the Multicentre Hemophilia Cohort Study. Among the 364 children (mean age 8 years), there were four deaths; two related to cancer, one to trauma, and the fourth to haemorrhage, end-stage liver disease and sepsis. Among the 387 HIV-uninfected adults (mean age 35 years) there were 29 deaths, with haemorrhage the leading cause of death, followed by hepatic, stroke and cancer deaths. Prognostic factors for all-cause mortality among the adults included haemophilia Type A with neutralizing antibodies [age-adjusted relative rate (RR) 3.1, 95% confidence interval (CI) 1.4-6.9] and serologic evidence of both hepatitis B and C virus (RR 4.1, 95% CI 0.97-17.6). Although hepatitis C viral load was slightly lower in patients with hepatitis B virus surface antigenaemia, it was unrelated to vital status. We conclude that causes of death and prognostic factors for current HIV-uninfected haemophilia patients are similar to those noted before the HIV epidemic. Better understanding, prevention and control of neutralizing antibodies and hepatitis infections may substantially improve longevity for people with haemophilia.
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PMID:Factors predictive of death among HIV-uninfected persons with haemophilia and other congenital coagulation disorders. 1219 76

The afimbrial AfaE-VIII adhesin is common among Escherichia coli isolates from calves with intestinal and/or extraintestinal infections and from humans with sepsis or pyelonephritis. The virulence genotypes of 77 Escherichia coli afa-8 isolates from farm animals and humans were compared to determine whether any trait of commonality exists between isolates of the different host species. Over half of the extraintestinal afa-8 isolates were associated with pap and f17Ac adhesin genes and contained virulence genes (pap, hly, and cnf1) which are characteristic of human extraintestinal pathogenic E. coli (ExPEC). PapG, which occurs as three known variants (variants I to III), is encoded by the corresponding three alleles of papG. Among the pap-positive strains, new papG variants (papGrs) that differed from the isolates with genes for the three adhesin classes predominated over isolates with papG allele III, which in turn were more prevalent than those with allele II. The data showed the substantial prevalence of the enteroaggregative E. coli heat-stable enterotoxin gene (east1) among afa-8 isolates. Most of the afa-8 isolates harbored the high-pathogenicity island (HPI) present in pathogenic Yersinia; however, two-thirds of the HPI-positive strains shared a truncated HPI integrase gene. The presence of ExPEC-associated virulence factors (VFs) in extraintestinal isolates that carry genes typical of enteric strains and that express O antigens associated with intestinal E. coli is consistent with transfer of VFs and O-antigen determinants between ExPEC and enteric strains. The similarities between animal and human ExPEC strains support the hypothesis of overlapping populations, with members of certain clones or clonal groups including animal and human strains. The presence of multiple-antibiotic-resistant bovine afa-8 strains among such clones may represent a potential public health risk.
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PMID:Extended virulence genotype of pathogenic Escherichia coli isolates carrying the afa-8 operon: evidence of similarities between isolates from humans and animals with extraintestinal infections. 1251 52

Systematic evaluations of anemia, thrombocytopenia, and coagulopathy are essential to identifying and managing their causes successfully. In all cases, clinicians should evaluate RBC measurements alongside WBC and platelet counts and WBC differentials. Multiple competing factors may coexist; certain factors affect RBCs independent of those that affect WBCs or platelets. Ideally, clinicians should examine the peripheral blood smear for morphologic features of RBCs, WBCs, and platelets that provide important clues to the cause of the patient's hematologic disorder. Thrombocytopenia arises from decreased platelet production, increased platelet destruction, or dilutional or distributional causes. Drug-induced thrombocytopenias present diagnostic challenges, because many medicines can cause thrombocytopenia and critically ill patients often receive multiple medications. If they suspect type II HIT, clinicians must promptly discontinue all heparin sources, including LMWHs, without awaiting laboratory confirmation, to avoid thrombotic sequelae. Because warfarin anticoagulation induces acquired protein C deficiency, thereby exacerbating the prothrombotic state of type II HIT, warfarin should be withheld until platelet counts increase to more than 100,000/microL and type II HIT is clearly resolving. The presence of a consumptive coagulopathy in the setting of thrombocytopenia supports a diagnosis of DIC, not TTP-HUS, and is demonstrated by decreasing serum fibrinogen levels, and increasing TTs, PTs, aPTTs, and fibrin degradation products. Increasing D-dimer, levels are the most specific DIC parameter and reflect fibrinolysis of cross-linked fibrin. Elevated PTs or a PTTs can result from the absence of factors or the presence of inhibitors. Clinicians should suspect factor inhibitors when the prolonged PT or aPTT does not correct or only partially corrects following an immediate assay of a 1:1 mix of patient and normal plasma. In addition to factor inhibitors, antiphospholipid antibodies (e.g., lupus anticoagulant) can produce a prolonged aPTT that does not correct with normal plasma but is overcome by adding excess phospholipid or platelets. Paradoxically, a tendency to thrombosis, not bleeding, accompanies lupus anticoagulants and the antiphospholipid antibody syndrome. Transfusion of red blood cells, platelets, or plasma products is sometimes warranted, but clinicians must carefully weigh potential benefits against known risks. In critically ill patients, administering RBCs can enhance oxygen delivery to tissues. Among euvolemic patients who do not have ischemic heart disease, guidelines recommend a transfusion threshold of HGB levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least 10.0 g/dL are unlikely to benefit from blood transfusion. The use of rHuEPO to increase erythropoiesis offers an alternative to RBC transfusion, assuming normal, responsive progenitor cells and adequate iron, folate, and cobalamin stores. Future research should examine whether clinical outcomes from rHuEPO use in critically ill patients are important and cost-effective. Because platelets play an instrumental role in primary hemostasis, platelet transfusions are often important in managing patients who are bleeding or at risk of bleeding with thrombocytopenia or impaired platelet function. Platelet transfusions carry risks, and decisions to transfuse platelets must consider clinical circumstances. Most important, platelet transfusions are generally contraindicated if the underlying disorder is TTP or type II HIT, because platelet transfusion in these settings may fuel thrombosis and worsen clinical signs and symptoms. Plasma products can correct hemostasis when bleeding arises from malfunction, consumption, or underproduction of plasma coagulation proteins. Choice of plasma product for transfusion depends on clinical circumstances. FFP is the most commonly used plasma product to correct clotting factor deficiencies, particularly coagulopathies that are attributable to multiple clotting factor deficiency states as in liver disease, DIC, or warfarin anticoagulation. PCC or rFVIIa that is administered in small volumes may provide advantages over FFP when coagulopathies require quick reversal without risk of volume overload. Factor concentrates can replace specific factor deficiencies. Recombinant FVIIa bypasses inhibitors to factors VIII and IX and vWF. Use of rFVIIa in managing hemostatic abnormalities from severe liver dysfunction; extensive surgery, trauma, or bleeding; excessive warfarin anticoagulation; and certain platelet disorders requires further study to determine optimal and cost-effective dosing regimens. Recombinant activated protein C reduces mortality from severe sepsis that is associated with organ dysfunction in adults who are at high risk for death (APACHE scores of at least 25). In severe sepsis, levels of protein C decrease, as do fibrinogen and platelet levels. Because of its anticoagulant effect, however, drotrecogin alfa may induce bleeding. Guidelines for drotrecogin alfa use must take into account bleeding risks.
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PMID:Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. 1471 Jun 93

Group B streptococci (GBS) (Streptococcus agalactiae) are a major cause of sepsis and meningitis in neonates and infants and of invasive disease in pregnant women, nonpregnant, presumably immunocompromised adults, and the elderly. Nine GBS serotypes based on capsular polysaccharide antigens have been described. The serotype distributions among invasive and colonizing isolates differ between pediatric and adult populations and have changed over time. Thus, periodic monitoring of GBS serotype distributions is necessary to ensure the proper formulation and application of an appropriate GBS vaccine for human use and to detect the emergence of novel serotypes. Since the mid-1990s, the proportion of GBS isolates that are nontypeable by standard serologic methods has increased, creating a need for more sensitive typing methods. We describe a typing method that uses DNA dot blot hybridization with probes generated by PCR from the GBS capsular genes for serotypes Ia, Ib, and II to VIII. PCR primers were designed to amplify type-specific GBS capsular gene sequences. Gene probes were constructed from the PCR products and used to classify isolates based on hybridization profiles. A total of 306 previously serotyped invasive and colonizing isolates were used to compare our dot blot capsular typing (DBCT) identification method with Lancefield serotyping (LS). A dot blot capsular type was assigned to 99% (303 of 306) of the isolates, whereas 273 of 306 isolates (89%) were assigned a Lancefield serotype. The overall agreement between the methods was 95% (256 of 270 isolates typeable by both methods). We conclude that the DBCT method is a specific and useful alternative to the commonly used LS method.
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PMID:Comparison of DNA dot blot hybridization and lancefield capillary precipitin methods for group B streptococcal capsular typing. 1471 45

Activated protein C (APC), a natural anticoagulant, is formed from protein C by the action of the thrombin-thrombomodulin (TM) complex on the endothelial cell surface. Endothelial protein C receptor augments the activation of protein C by the thrombin/TM system. APC inactivates the activated form of coagulation factors V and VIII in the presence of protein S. Administration of APC reduced the pulmonary vascular injury and hypotension as well as the coagulation abnormalities by inhibiting production of the tumor necrosis factor-alpha (TNF-alpha) in rats given endotoxin (ET). These therapeutic effects of APC could not be attributed to its anticoagulant effects. APC inhibited ET-induced TNF-alpha production in human monocytes by inhibiting activation of nuclear factor K-B and activator protein-1 in vitro. Administration of the human plasma-derived APC ameliorated coagulation abnormalities without any adverse effects in patients with disseminated intravascular coagulation (DIC). Recombinant APC was reported to reduce the mortality of patients with severe sepsis, and the therapeutic effect was more marked in such patients with overt DIC than those without it. These observations strongly suggest that APC plays important roles in the regulation of inflammation as well as coagulation. Both anti-inflammatory and anticoagulant properties of APC might contribute to the therapeutic usefulness in patients with severe sepsis.
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PMID:Regulation of inflammatory responses by activated protein C: the molecular mechanism(s) and therapeutic implications. 1506 50

Activated protein C (APC), a natural anticoagulant, is formed from protein C by the action of thrombin bound to thrombomodulin on the endothelial cell surface. APC regulates the coagulation system by inactivating the activated form of factors V and VIII in the presence of protein S. Tumor necrosis factor-alpha (TNF-alpha) plays critical roles in the development of disseminated intravascular coagulation, acute respiratory distress syndrome and shock in sepsis by inducing endothelial cell damage through activation of neutrophils. APC reduces the pulmonary endothelial cell injury and hypotension in rats administered endotoxin (ET) by inhibiting TNF-alpha production through inhibition of its transcription. Furthermore, APC reduces the ischemia/reperfusion-induced renal injury and the stress-induced gastric mucosal injury in rats. Inhibition by APC of the endothelial cell damage inhibited the decrease in the endothelial production of prostacyclin in vivo. These therapeutic effects could not be attributed to its anticoagulant effects, but to inhibition of TNF-alpha production. APC inhibits ET-induced TNF-alpha production in vitro in human monocytes by inhibiting activation of NFkappaB and AP-1 by inhibiting degradation of IkappaB and mitogen-activated protein kinase pathways, respectively. Recombinant APC was reported to reduce the mortality of patients with severe sepsis. These observations strongly suggest that APC might be involved not only in regulation of the coagulation system, but in regulation of inflammatory responses by preventing endothelial cell injury. Furthermore, APC reduced the spinal cord injury induced by compression-trauma or ischemia/reperfusion by inhibiting TNF-alpha production in rats, suggesting that APC may be a potential therapeutic agent for spinal cord injury in which only limited therapeutic measures are currently available.
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PMID:Prevention of endothelial cell injury by activated protein C: the molecular mechanism(s) and therapeutic implications. 1532 May 13

It has been hypothesized that the protein C pathway is a pivotal link between the inflammation and coagulation cascades. The demonstration that a survival benefit is associated with administration of drotrecogin alfa (activated) (recombinant human activated protein C [APC]) in severe sepsis patients has provided new insights into the protein C pathway. APC was originally identified based on its antithrombotic properties, which result from the inhibition of activated Factors V and VIII. In the early 1990s, any potential anti-inflammatory properties of APC were thought to relate primarily to its inhibition of thrombin generation. However, the mid-1990s saw the identification of the endothelial protein C receptor (EPCR), which has subsequently been shown to be neither endothelial specific nor protein C specific, but has a primary function as a cofactor for enhancing the generation of APC or behaving as an APC receptor. Thus, the potential biologic activities of APC can be classed into two categories related either to the limiting of thrombin generation or to cellular effects initiated by binding to the EPCR. Intracellular signaling initiated by binding of APC to its receptor appears to be mediated by interaction with an adjacent protease-activated receptor (PAR), or by indirect activation of the sphingosine 1-phosphate pathway. Based mostly on in vitro studies, binding of APC to its receptor on endothelial cells leads to a decrease in thrombin-induced endothelial permeability injury, while such binding on blood cells, epithelial cells, and neurons has been shown to inhibit chemotaxis, be anti-apoptotic, and be neuroprotective, respectively. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study, drotrecogin alfa (activated) was associated with improved cardiovascular function, respiratory function, and a prevention of hematologic dysfunction. This article discusses the way in which the interactions of APC may alter the microcirculation.
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PMID:New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated). 1616 74

Venous thrombosis can be the source of emboli, a significant health risk encountered throughout surgical and medical clinics. Taurolidine is an antimicrobial agent used to prevent intraabdominal adhesion formation and sepsis in experimental and clinical trials. The aim of this study is to evaluate effect of taurolidine on experimental thrombus formation and make a comparison with low-molecular weight heparin. Four groups of ten Wistar-Albino rats (300-350 g) were used; with the first and second groups each being administered 10 and 20 mg of taurolidine, the third group low-molecular weight heparin and the fourth group saline solution (control group) respectively. Experimental thrombus formation was performed in rats in the area of the abdominal inferior vena cava by using a combination of stasis and hypercoagulability described by Wessler et al. [Wessler, S., Reimer, S.M., Sheps, M.C., 1959. Biologic assay of a thrombosis inducing activity in human serum. J. Appl. Physiol. 14:943-946.]. Thrombocyte count, the weight of thrombus, prothrombin time and activated partial thromboplastin time and activities of coagulation factors were measured and compared across groups. Thrombus weights in the taurolidine treated groups were lower than the control group and greater than the low-molecular weight heparin treated group. Taurolidine was found to decrease activities of coagulation factors V, VIII, IX, XI and XII. Taurolidine showed no effect on activated partial thromboplastin time and prothrombin time values; however, it decreased thrombus weight, but not as much as low-molecular weight heparin. The cause of these findings in our study may be related to the minimized effect of taurolidine on factor II, VII, and X activities. These effects likely render the agent ineffective in the prevention of venous thrombosis. Taurolidine was found to be less effective than low-molecular weight heparin in prevention of thrombus formation.
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PMID:The effect of taurolidine on experimental thrombus formation. 1796 49

OUR CONCLUSIONS FROM THE LITERATURE AND OUR OWN EXPERIMENTS MAY BE SUMMARIZED AS FOLLOWS: I. Blood for bacteriological examination during life should be taken directly from the veins and in considerable quantity. II. Resorption of toxines is the most important feature in cases of sepsis; pyogenie bacteria invade the general circulation in a rather small proportion even of severe eases, and, as a rule, late in the course of the disease. III. A general infection by the pnenmococcus can be demonstrated occasionally in the late stages of acute lobar pneumonia. IV. The value of blood cultures as a means of diagnosis in obscure cases of sepsis is limited by the fact that invasion of the blood by the specific organism cannot be demonstrated during life in the majority of cases. Positive cultures are very valuable; negative cultures do not exclude local septic infections. V. The detection of specific bacteria in the blood of cases of sepsis and of pneumonia gives a very unfavorable prognosis in most cases. VI. General terminal infections with pyogenic cocci occasionally occur as an immediate cause of death in chronic disease. Local infections processes play this part more frequently. VII. As far as our experiments have shown, invasion of the blood by bacteria during the death agony, with subsequent distribution of the genus to the organs by the circulation, is a rather uncommon occurrence. VIII. Owing to the relative infrequency of agonal invasion, we believe that in the majority of cases where the autopsy is performed promptly after death, the bacteria which are found in the organs succeeded in reaching these organs previously to the death agony, and are associated with the course of the disease. IX. The presence of bacteria in the organs of late autopsies is due in many cases to post-mortem extension from one organ to another, and in some cases to the post-mortem growth of small numbers of genus which were distributed to the organs by means of the circulation.
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PMID:CULTURES FROM THE BLOOD In SEPTICAEMIA, PNEUMONIA, MENINGITIS AND CHRONIC DISEASES. 1986 18


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