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)

Disseminated intravascular coagulation (DIC) or renal damage associated with septicemia was induced in rats by ligating the cecum or by injecting endotoxin. In the septicemia model, the number of E. coli and Bacteroides spp in the blood increased concomitantly with an increase of endotoxin. In this model the development of hypercoagulability with mild fibrinolysis was observed. Histopathologic findings in the kidneys, including the formation of microthrombi in the glomeruli and the vacuolization and dilatation of renal tubular cells, suggest the development of mild DIC. In the endotoxin-induced DIC model, both remarkable state of hypercoagulability and fibrinolysis were observed with fibrin thrombi in glomeruli. The administration of the platelet-activating factor antagonist, CV-6209, or of human antithrombin III, ameliorated DIC significantly by limiting the increases in prothrombin time, activated partial thromboplastin time and fibrin degradation products. These agents significantly reduced the deposition of fibrin in the glomeruli and significantly prolonged the survival time of the endotoxin injected rats. These observations suggest that the PAF antagonist CV-6209 and ATIII merit clinical evaluation in the management of DIC caused by septisemia.
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PMID:Effect of a platelet activating factor antagonist and antithrombin III on septicemia and endotoxemia in rats. 206 2

Fibrin deposition in response to bacterial peritonitis appears to predispose to residual infection in the peritoneal cavity. Our previous studies have demonstrated that intraperitoneal fibrinolysis using human recombinant tissue plasminogen activator (t-PA) prevented abscess formation in a rat intra-abdominal sepsis model. To investigate the potential adverse side effects of its use in the peritoneal cavity, the effect of t-PA on colonic anastomotic wound healing and on systemic coagulation parameters was examined in the rat. T-PA did not adversely affect colonic healing five and ten days after anastomosis. In animals infected intraperitoneally at the time of the anastomosis, t-PA reversed the inhibition of healing induced by perianastomotic abscesses at five days. This effect was mediated by the ability of t-PA to prevent perianastomotic abscess formation. After intraperitoneal administration, t-PA had no effect on prothrombin and partial thromboplastin times in either uninfected or infected animals and there was no evidence of clinical bleeding related to its use. These studies suggest that intraperitoneal fibrinolysis using t-PA may provide a safe, effective form of adjuvant therapy in the management of fibrinopurulent peritonitis.
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PMID:Tissue plasminogen activator reverses the deleterious effect of infection on colonic wound healing. 210

The detection of TATC may inform about the presence of thrombin generation and, and hence of a pre-thrombotic status. An ELISA test (Enzygnst TAT) has been developed here in order to evaluate the predictive role played by TATC, and it was applied on 182 patients who distributed in 14 with cirrhosis of the liver, 11 with sepsis, 17 with chronic arterial insufficiency, 55 with neoplasms, 9 with thrombosis, 15 in postoperative period, 15 with pneumonia, 16 with disseminated intravascular coagulation (DIC), 14 with multiple injuries and 16 with pancreatitis. TATC levels were significantly increased in all groups with regard to the control group. Patients with thrombosis, sepsis, multiple injuries, DIC and in the postoperative period showed especially high TATC figures. No correlation between TATC and fibrinogen, platelet count, activated partial thromboplastin time or prothrombin complex assay was found in the post-operative patient-group. It was concluded that TATC are a good indicator of hypercoagulability.
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PMID:[Detection of thrombin-antithrombin complexes in hypercoagulability conditions. Analysis of 182 cases]. 229 Nov 47

A polyethylene glycol conjugate of L-asparaginase (PEGLA) was administered to 21 patients with refractory non-Hodgkin's lymphoma. The dose given was 2,000 mu/m2 intramuscularly every 2 weeks. Eligibility required at least one prior trial of chemotherapy and ambulatory performance status. At entry, all patients had measurable lesions and documented disease progression. The median age of the patients was 61 years; 18 (86%) were ambulatory with minimal symptoms, 12 patients (57%) had 3 or more prior regimens, and 13 (62%) had stage IV disease. Histologic subtype was low grade in 11 patients (52%), intermediate in 7 (33%), high grade in 2 (10%) and unclassifiable in one (5%). There were two partial responses (11%) noted (95% confidence interval of response of 1-30%). Eleven patients (52%) were removed from study due to disease progression. Nine patients (43%), required removal for toxicity (7 for protracted nausea and vomiting and 2 for confusion). One patient died of sepsis while on study but this was not considered drug related. Almost one third of patients complained of fatigue or loss of appetite. Nausea and vomiting occurred in approximately half the patients and was moderate to severe in 9. Diarrhea and abdominal pain were also noted in one-third of those treated. Changes in the partial thromboplastin time and fibrinogen were noted in most patients but resulted in no bleeding complications. In this trial, PEGLA displayed modest activity in a heterogenous group of patients with progressive non-Hodgkin's lymphoma.
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PMID:A phase II trial of PEG-L-asparaginase in the treatment of non-Hodgkins lymphoma. 234 67

We have evaluated the quantitative relationship between lipopolysaccharide (LPS, endotoxin), fibrinopeptide A (FPA), antithrombin (AT), protein C (PC) and extrinsic pathway inhibitor (EPI) in plasma from 39 consecutively admitted patients with systemic meningococcal disease (SMD). The most severely ill patients with fulminant meningococcal septicemia (n = 13, 6 dead) had significantly (p less than 0.01) higher plasma levels of LPS and FPA and lower levels of PC and AT on admission as compared with the less severe clinical presentations (n = 26, 1 dead). The levels of EPI on admission were significantly (p less than 0.05) higher in nonsurvivors vs survivors with fulminant septicemia. As the disease progressed, the levels of LPS, FPA, AT and PC declined, while the levels of EPI increased. Three of six nonsurviving septicemic patients had levels of EPI greater than 200% within 16 hours of admission vs two of 30 survivors (p = 0.02). The results suggest that increasing levels of LPS in SMD elicit increasing consumption coagulopathy, contributing to the organ pathophysiology. The kinetics of EPI, inhibiting the thromboplastin-FVIIa-FXa complex, differs markedly from the kinetics of AT and PC i.e. increases as opposed to decreases.
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PMID:The quantitative association of plasma endotoxin, antithrombin, protein C, extrinsic pathway inhibitor and fibrinopeptide A in systemic meningococcal disease. 251 Mar 54

Between October 1985 and March 1988, 16 patients received the Jarvik-7 total artificial heart as an interim device before transplantation. Ten patients were afflicted with cardiomyopathy, and 6 had end-stage ischemic disease. All but 1 were men; the mean age was 47 years (range, 27 to 59 years). Thirteen patients developed cardiogenic shock despite the use of intravenous inotropic agents (mean, 23 days; range, two to 83 days) and the intraaortic balloon pump (mean, 13 days; range, two to 65 days). Three other patients became candidates because of failed transplantation. The 100-mL Jarvik-7 device was used in the first 3 patients; all subsequent recipients were treated with the 70-mL Jarvik-7. Postoperative anticoagulation was designed to keep the partial thromboplastin time between 2 and 2.5 times control. The control values were obtained during administration of heparin and dipyridamole. In all cases the function of the total artificial heart was adequate to support the needs of the recipient, and there were no mechanical difficulties with the device or the drive system. The average time of implantation was 9 days (range, one to 35 days). Two patients died before transplantation, 1 with sepsis from fungus and the other with hemorrhage from a torn pulmonary arterial anastomosis. Fourteen patients received cardiac allografts, and 7 continue to survive without restrictions. Infection within the mediastinum caused the death of 4 patients after transplantation; in 3 of these mediastinitis was not recognized before transplantation but occurred within the first 2 weeks after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interim use of the Jarvik-7 artificial heart: lessons learned at Presbyterian-University Hospital of Pittsburgh. 264 3

Gram-negative septicemia/endotoxemia remains a serious clinical disorder that is often complicated by disseminated intravascular coagulation (DIC). Plasma antithrombin-III (AT-III) levels usually decrease during gram-negative septicemia/endotoxemia, and even moderate decreases in this major inhibitor of the coagulation system are associated with serious DIC. We demonstrated in an earlier study that prophylactic treatment of rats with 250 U/kg of AT-III followed by endotoxin challenge markedly attenuates DIC, indices of organ damage, and metabolic dysfunction. The present study was to determine whether treatment with 250 U/kg AT-III 1 hr after endotoxin challenge would be similarly efficacious. Rats treated with 250 U/kg of AT-III inactivated by human sputum elastase (ATX) served as protein controls. Blood samples for analysis were obtained 4 hr after AT-III or ATX treatment (5 hr after endotoxin challenge). Rats in the ATX treatment group exhibited abnormalities characteristic of endotoxemia, i.e., decreased fibrinogen levels and platelet counts, increases in prothrombin time and activated partial thromboplastin time, elevated serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase (AKP), and hypoglycemia. Treatment with AT-III markedly and significantly (P less than .05) attenuated all of these abnormalities, although survival was not increased. This study strongly suggests that supplementation of plasma AT-III is efficacious after the development of sepsis, although not as efficacious as prophylactic treatment.
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PMID:Antithrombin-III treatment limits disseminated intravascular coagulation in endotoxemia. 273 21

The levels of protein C (PC) and other coagulation factors were monitored during endotoxin-induced disseminated intravascular coagulation (DIC) in the dog. Initial evaluation of the effectiveness of intradermal administration of bolus endotoxin quantities into the dog, demonstrated induction of DIC in the canine, without the severe side effects associated with bacterial sepsis. Quantitative determination of canine plasma protein C levels were performed using a multiple step amidolytic assay, that included a specific precipitation of the vitamin K-dependent proteins from citrated plasma, followed by thrombin activation (and neutralization) and subsequent measurement of the activated protein C (APC) by chromogen hydrolysis. This investigation demonstrated, that over a twenty-four hour interval, intradermal administration of endotoxin produces a gradual decrease in the PC activity levels, concomitant with a significant reduction in the Factor V, Factor VIII and fibrinogen levels and platelet count, and a prolongation of the Prothrombin Time and Partial Thromboplastin Time. During the first 6 hours, protein C levels fell below the pre-levels and remained significantly lower in the surviving dogs. Thus, this endotoxin-induced DIC animal model permits evaluation of various hemostatic parameters, yet diminishes the severe clinical findings associated with DIC.
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PMID:Protein C activity levels in endotoxin-induced disseminated intravascular coagulation in a dog model. 278 30

The activity of the extrinsic pathway inhibitor (EPI), which is the factor-Xa-dependent inhibitor of the factor VIIa-tissue thromboplastin complex, was serially determined in 13 patients with postoperative/posttraumatic septicemia, and compared to the activity of antithrombin (AT), heparin cofactor II and protein C (PC). In the survivors (n = 8), initial low values for all the inhibitors normalized during recovery. In the demises (n = 5), a progressive increase in EPI activity was observed until death, whereas progressive decreases were observed for the other inhibitors. No correlation was found between the inhibitor values and the endotoxin concentration. We conclude that EPI activities are increased in the late course of fatal septicemia. Apparently, a large EPI-AT gap is a severe prognostic indicator in such patients.
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PMID:Extrinsic pathway inhibitor in postoperative/posttraumatic septicemia: increased levels in fatal cases. 280 38

A patient with T-polyagglutinable red cells and a severe coagulopathy provided an opportunity to observe the results of plasma transfusion in the face of T-activation. The patient was a 52-year-old Navajo Indian with a perforated gall bladder and related sepsis due to Clostridium perfringens. The gall bladder was removed surgically. Postoperatively, he had severe thrombocytopenia, and prolonged partial thromboplastin and prothrombin times. The patient's red cells were agglutinated by Arachis hypogaea and Glycine soja lectins but were unagglutinated by extracts of Salvia horminum, Salvia sclarea, and Bandeiraea simplicifolia. No untoward reactions or any evidence of hemolysis were observed when the patient was given platelet concentrates and 4 units of single-donor plasma. Serial plasma hemoglobin and haptoglobin levels documented that there was no hemolysis. His coagulopathy responded, and he had a successful surgical re-exploration and recovery. This case documents that serious adverse consequences do not necessarily follow transfusion of plasma in a recipient with T-activated red cells. T-activation is a relative but not absolute contraindication to plasma transfusion.
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PMID:Uneventful administration of plasma products in a recipient with T-activated red cells. 286


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