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

It has been demonstrated that oxidized regenerated cellulose promptly and markedly reduces the bacterial census of ten different strains of common pathogens when exposed to them in vitro. This was not true of two other hemostatic agents tested, namely, absorbable gelatin sponge and topical thrombin. Wounds in guinea pigs in which oxidized regenerated cellulose was placed and infected with one of three pathogens had healing per primum in 39 of 40 instances. In similar control wounds and incisions in which absorbable gelatin sponge was placed, sepsis of the wound developed in 19 of 20 of the control group and in 39 of 40 guinea pigs in the absorbable gelatin sponge group.
 ...
PMID:Antibacterial activity of oxidized regenerated cellulose. 17 40

Numerous studies have demonstrated that reticuloendothelial system (RES) depression induced by colloid blockade increases susceptibility to circulatory shock following trauma and sepsis. Recent data have suggested that this may relate to the failure of the RES to clear potentially embolic material derived from activation of the hemostatic system. The present study thus compared the hypotensive response precipitated by trauma or sepsis with that resulting from induction of intravascular coagulation. Mean arterial blood pressure (MABP) was monitored for 120 minutes after sublethal NCD trauma and after intra-aortic injection of live E coli (approximately 10(10) organisms per rat), E coli endotoxin (0.1 mg/100 gm), or bovine thrombin (10 units/100 gm) in 400-500 gm rats 30 minutes after RE blockade (50 mg/100 gm gelatinized lipid colloid) or saline injection. All rats were anesthetized with sodium pentobarbital. No hypotension was observed in blockaded control rats. After trauma, MABP decreased by 20 minutes after injury and recovered to normal levels by 1 hour post-trauma. MABP decreased in blockaded rats after trauma and remained diminished through 2 hours. After live E coli endotoxin or thrombin, both the normal and the blockaded groups underwent an initial hypotension of similar magnitude. A second period of hypotension was much more pronounced in the RE-blockaded animals. Reduced MABP persisted in these animals through 2 hours. These data indicate that RE blockade enhances the hypotensive response to intravascular coagulation and that resulting from trauma or sepsis. This effect was especially apparent during the second phase of hypotension during sepsis and intravascular coagulation. It was suggested that the RES manifests some protective effect against the agents inducing this secondary hypotensive response.
 ...
PMID:Effect of reticuloendothelial blockade on the development of hypotension after trauma, sepsis, and intravascular coagulation. 26 5

The unexplained occurrence of thrombocytopenia in cases of Gramnegative sepsis in man led us, in the light of animal experiments indicating the blood platelet as the target cell for endotoxin, to examine the effect of Salmonella enteritidis lipopolysaccharide B on human platelets. Human platelets were separated from a coat of plasma proteins by Sepharose 2B filtration or by a combined procedure of albumin gradient and Sepharose 2B filtration. The action of endotoxin on human platelets resulted in membrane changes manifested by dose-dependent release of [3H]serotonin and adenine nucleotides. Cytoplasmic marker, lactic dehydrogenase, and lysosomal marker, beta glucuronidase, were retained indicating that the release reaction was selective. Release of [3H]serotonin was specific for endotoxin since other particulates, zymosan and erythrocyte stroma, were without effect. Endotoxin, added to gel-filtered human platelets, induced a significant evolution of platelet factor 3 procoagulant activity. Preincubation of endotoxin with a membrane-rich homogenate of human platelets inhibited its labilizing effect on human platelets thus suggesting an interaction between endotoxin and the platelet membrane itself. Other plausible factors in this interaction [fibrinogen, adenine nucleotides, thrombin, sialic acid residues, and IgG] were eliminated on the basis of a series of control experiments. From the negligible effect of aspirin and indomethacin, we may infer that the interaction of endotoxin with platelets does not depend on the platelet prostaglandin synthesis pathway. The direct interaction of endotoxin with the human platelet membrane comprises a new mechanism which may help to clarify the pathogenesis of vascular and haemostatic disorders accompanying bloodstream infections due to Gram-negative bacteria.
 ...
PMID:Membrane changes in human platelets induced by lipopolysaccharide endotoxin. 32 97

The diagnosis of defibrination syndrome in shock, sepsis and neonatal hypoxia is based, in addition to the clinical picture, upon a few parameters of the hemostatic system, which, in part as global tests, provide information about the course of coagulation. The parameters measured are partial thromboplastin time, thromboplastin time, plasma thrombin time, fibrinogen, thrombin-coagulase and reptilase times as well as platelet count. Normal values of these laboratory parameters were established for healthy newborns 1--5 days of age, and for healthy adults. It is suggested that especially partial thromboplastin time, the thrombin-coagulase and reptilase times, the latter influenced by fibrinolysis cleavage products, are representative for the tentative diagnosis of disseminated intravascular coagulation with fibrinolysis syndrome (DICFS). The platelet fall often lags 1--2 days behind the event. Moreover normal values for newborns, are markedly higher than those for older children or adults. In the presence of DICFS, a low-dose heparin therapy is immediately initiated. If completed defibrination is manifest, therapy is supplemented with urokinase and streptokinase, For DICFS with congenital sepsis, an exchange transfusion with heparinized fresh blood is the treatment of choice.
 ...
PMID:[Diagnostic therapeutic problems of defibrination syndrome in shock, sepsis, and neonatal hypoxia (author's transl)]. 32 24

This chapter has provided a review of available literature regarding alterations of hemostasis associated with CPB. The primary pathology of altered hemostasis during CPB appears to be two-fold: (1) a functional platelet defect of unclear etiology, which occurs in virtually all patients, and (2) a primary hyperfibino(geno)lytic defect which occurs in the majority of patients undergoing cardiopulmonary bypass. Significant thrombocytopenia does not appear to be a consistent problem, and is probably a function of perfusion technics; this may, however, be an important source of hemorrhage in some instances. Although hyperheparinemia, heparin rebound, and protamine excess have occasionally been incriminated as sources of hemorrhage during CPB, no well documented cases appear in the literature. Likewise, although DIC gained popularity in early reports of CPB hemorrahge, it appears that this syndrome rarely, if ever, arises as a consequence of CPB alone; it can be seen, however, in CPB patients who are provided a triggerin situation for DIC, such as shock, sepsis, or hemolytic transfusion reaction. It is likely that many reported alterations of hemostasis during CPB which were concluded to represent DIC actually were due to hyperfibino(geno)lysis. The key to prevention of CPB hemorrhage rests simply in obtaining an adequate preoperative workup. Of extreme importance is an adequate history with respect to bleeding tendencies in both patient and family; of equal importance is a careful history regarding antiplatelet drugs. A careful physical examination, searching for clues of a real or potential bleeding diathesis, also can often prevent catastrophic cases of CPB hemorrhage. Lastly, an adequate presurgical laboratory screen must be performed; in addition to the usual prothrombin time, partial thromboplastin time, and platelet count, a thrombin time and standardized template bleeding time must be added. The addition of these two simple modalities will insure against significant defects in fibrinogen, the fibrinolytic system, vascular function, and platelet function. When CPB hemorrhage occurs, simple laboratory screening will usually allow for a quick hemostasis evaluation. The parameters recommended in this review will distinguish between surgical and nonsurgical bleeding and should, therefore, allow for a quick decision regarding necessity for reexploration and the adequacy of hemostasis if reexploration is needed. In addition, this screen will distinguish between difficulties with heparin, protamine, and the fibrinolytic system. The vast majority of nonsurgical hemorrhages during CPB is due to a functional platlet defect, primary hyperfibrino(geno)lysis, or a combination of these. The quick administration of platelet concentrates, while awaiting laboratory evaluation, will control or significantly blunt most instances of CPB hemorrhage. If platelets fail to control bleeding, and reasonable laboratory evidence of primary hyperfibrino(geno)lysis is present, antifibrinolytics should then be used...
 ...
PMID:Alterations of hemostasis associated with cardiopulmonary bypass: pathophysiology, prevention, diagnosis, and management. 79 78

The DIC syndrome is the most common cause of an abnormal hemorrhage tendency during pregnancy and the puerperium and reflects systemic activation of the coagulation cascade by circulating thromboplastic material, with secondary activation of the fibrinolytic system. Its presence in a pregnant patient almost invariably is evidence of an underlying obstetric disorder such as abruptio placentae, eclampsia, retention of a dead fetus, amniotic fluid embolism, placental retention or bacterial sepsis. Diagnosis of the DIC syndrome rests on the demonstration of reduced levels of fibrinogen and platelets, prolongation of the thrombin, prothrombin and partial thromboplastin times, and the presence of fibrin/fibrinogen degradation products (FDP) in the serum. Therapy consists of prompt removal of the source of procoagulant material, replacement of depleted clotting factors and, in some cases, anti-coagulation with heparin.
 ...
PMID:Disseminated intravascular coagulation in pregnancy. 91 82

Serial measurements of coagulation activity, platelet counts, and platelet aggregation were done in patients with full-thickness burns involving 25% or more of body surface area to detect specific changes that might correlate with the onset of septicemia. Mean and maximal values for prothrombin time, partial thromboplastin time, thrombin time, activities of factor V and factor VIII, and concentrations of fibrinogen and fibrinogen-related antigens observed in the presence of bacterial septicemia did not differ significantly from those observed in the absence of septicemia. Mean platelet counts were significantly less with sepsis, but values in individual subjects were not indicative of the presence of septicemia. By contrast, platelet aggregation in response to adenosine diphosphate, epinephrine, and collagen always became severely abnormal with the onset of septicemia but not in the absence of sepsis.
 ...
PMID:Platelet aggregation as a sign of septicemia in thermal injury. A prospective study. 94 30

Disseminated intravascular coagulation (DIC) is a syndrome caused by the systemic generation of thrombin. Most cases are due to pathological activation of the intrinsic coagulation systems (e.g. in sepsis), and/or the extrinsic system (e.g. in malignancy and head trauma). Diagnosis is made by finding abnormalities in at least 3 of 4 laboratory values, namely prothrombin time, platelet count, fibrinogen and fibrinogen/fibrin degradation products. The most common clinical manifestation of DIC is bleeding, with thrombosis in less than 10% of acute cases but more frequently encountered in chronic DIC associated with malignancy. Acute DIC must first be treated by specific therapy of the underlying disease and general support measures. If serial clinical and laboratory monitoring improves, no further treatment is required. If severe or life-threatening haemorrhage occurs or a thrombotic event ensues, heparin anticoagulation followed by aggressive replacement with platelets, fresh plasma and possibly cryoprecipitate is indicated. Heparin doses should be 'therapeutic' (i.e. adequate to overcome the coagulant forces that may have produced a relative heparin-resistant state in the blood). Chronic DIC with haemorrhage, or more usually thrombosis, should also be treated with heparin; warfarin is ineffective. If DIC persists because, for example, a tumour does not regress, long term outpatient subcutaneous heparin therapy may be required.
 ...
PMID:Disseminated intravascular coagulation. Approach to treatment. 128 66

To estimate the degree of coagulopathy in abdominal sepsis, we measured the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) by the enzyme-linked immunosorbent assay in 38 patients with disseminated intravascular coagulation (DIC). In 20 patients with DIC due to abdominal sepsis, plasma levels of F1 + 2, TAT and PIC were 2.6 nmol/l, 27.9 micrograms/l and 1.5 micrograms/ml, respectively, with a mean antithrombin III (AT III) activity of 41.7%. F1 + 2, TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 micrograms/l, 8.8 micrograms/ml and 70.9% in 18 patients with DIC as the result of malignancy. Though AT III levels in DIC due to sepsis were lower than those in DIC due to malignancy, the levels of F1 + 2, TAT and PIC in the former were not significantly more increased than those in the latter. The plasma levels of F1 + 2 were positively correlated with TAT and PIC in DIC patients with malignancy; however, there was no correlation between F1 + 2 and TAT or PIC in DIC patients with sepsis. In addition, the levels of serum albumin in the two groups were similar. These results suggest that activation of coagulation and fibrinolytic systems may not be so prominent in cases of DIC due to abdominal sepsis, compared to related events in DIC due to malignancy. It is also suggested that the depletion of AT III in cases of sepsis is not only caused by a consumption related to intravascular coagulation or to an alternate distribution of protein.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Coagulopathy in disseminated intravascular coagulation due to abdominal sepsis: determination of prothrombin fragment 1 + 2 and other markers. 138 63

In a rhesus monkey endotoxin sepsis model established by intravenous administration of 300 mg/kg D-galactosamine and 0.1 microgram/kg lipopolysaccharide from Salmonella abortus equi, hemodynamic, respiratory, metabolic and hematologic variables; levels of blood gases; monkey leukocyte elastase levels, and blood plasma concentrations of tumor necrosis factor--alpha (TNF) were monitored for 6 hours after administration, and again after 24 hours. Thirty minutes after administration of lipopolysaccharide, either 15 mg/kg anti-TNF monoclonal antibody (MoAB; n = 6) or vehicle placebo (saline solution; n = 4) were given intravenously. During this short-term experiment the organ functions were not different between the treatment groups. However, anti-TNF MoAb afforded morphologic protection from heart, lung, liver, and kidney damage after lipopolysaccharide challenge. Coagulation responses (platelet count and levels of fibrinogen, antithrombin III, and thrombin-antithrombin III complex) were smaller in anti-TNF MoAB-treated monkeys. Plasma TNF levels (WEHI cell cytotoxicity assay) reached a peak (350 pg/ml) 60 minutes after lipopolysaccharide administration in vehicle control subjects but no TNF was detected in the anti-TNF MoAB-treated monkeys. All control animals died 67 +/- 30 hours after lipopolysaccharide administration from multiorgan failure. On the contrary, all anti-TNF MoAB-treated animals survived 14 days (p > 0.005 vs placebo group mortality). Thus in short-term monkey experiments our study indicates protection against lipopolysaccharide-induced endotoxin sepsis by anti-TNF MoAB, which may have clinical relevance for the treatment of human septicemia.
 ...
PMID:Monoclonal antibody to tumor necrosis factor--alpha prevents lethal endotoxin sepsis in adult rhesus monkeys. 140 33


1 2 3 4 5 6 7 8 9 10 Next >>