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)

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

Plasma and serum from patients with liver disease and elevated fibrin(ogen) degradation product (FDP) levels as measured by latex agglutination were analyzed by immunoblotting to characterize the FDP in these patients. An antihuman fibrinogen antibody was used that recognizes fibrinogen, fibrin monomer, soluble high molecular weight fibrinogen and fibrin polymers, as well as high molecular weight cross-linked degradation fragments, and the smaller fragments X, Y, D-dimer, D, and E. The analytic procedures were validated with plasma and serum from patients known to have intravascular fibrinolysis associated either with disseminated intravascular coagulation (DIC) or with thrombolytic therapy. The samples demonstrated a spectrum of plasmin degradation fragments on the immunoblots. Twenty-eight of 35 patients with liver disease (80%) had no evidence of plasmin degradation fragments in their plasma or serum. The cause of the elevated FDP levels as measured by latex agglutination was thought to be fibrin monomer or unclottable fibrinogen that was retained in the sera of some of these patients. Seven patients (20%) were found to have circulating plasmin degradation fragments. In addition to liver disease, however, these patients all had an illness (sepsis, shock, and pancreatic carcinoma) independently associated with intravascular coagulation and fibrinolysis. Three patients who lacked plasmin fragments also had pancreatic carcinoma or sepsis. The two groups of liver disease patients could not be clearly differentiated on the basis of clinical or laboratory evidence, but the blotting procedure proved to be a useful discriminator.
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PMID:Analysis of elevated fibrin(ogen) degradation product levels in patients with liver disease. 293 48

Renal disease with distinctive pathologic features developed in two young women who had placental site trophoblastic tumors. The renal abnormalities were manifested by proteinuria in both cases and by hematuria in one case; blood pressure was elevated in one of the patients. Pathologic examination of the kidneys showed distinctive glomerular abnormalities, characterized mainly by the presence of occlusive eosinophilic deposits in many of the glomerular capillary lumina, most of which stained for fibrinogen-related antigens and IgM by immunohistochemical techniques. Ultrastructural examination showed the deposits to consist mainly of granular material that contained packets of fibrillar material with the appearance of fibrin. The uterine tumors were composed of mononucleated and multinucleated cells with abundant cytoplasm that infiltrated between the muscle bundles of the myometrium; in both tumors there was prominent deposition of eosinophilic material that had the tinctorial properties of fibrin and that stained for fibrinogen and IgM in immunoperoxidase studies. The renal abnormalities disappeared after hysterectomy in one case; the other patient, who was receiving chemotherapy and had disseminated intravascular coagulation, died with leukopenia and sepsis. The clinical and pathologic features in these cases suggest that the renal abnormalities were related to the uterine tumors and that the production of immune complexes and/or the activation of intravascular coagulation by the tumors were pathogenetic mechanisms.
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PMID:A distinctive glomerular lesion complicating placental site trophoblastic tumor: report of two cases. 298 14

Children undergoing ABMT, a procedure which entails massive doses of chemotherapy along with total-body irradiation, are candidate to develop severe gastrointestinal toxicity and prolonged anorexia requiring administration of Parenteral Nutrition (PN) for variable periods. We report a series of 35 consecutive children affected by malignancies who underwent 37 courses of PN after ablative therapy followed by ABMT. Age ranged from 8 months to 17 years; 16 were females, 19 males. There were 23 cases of neuroblastoma, 5 of Wilms' tumor, 3 of acute myelogenous leukemia, 2 of Ewing's sarcoma, 1 case each of rhabdomyosarcoma and acute lymphoblastic leukemia. All patients developed severe neutropenia for 9-42 days (median 18 d). Fever occurred in all patients; sepsis was documented in 10. Duration of PN ranged from 10 to 64 days (23 +/- 9; mean +/- SD). PN solution, containing crystalline L-Aminoacids (8.5%) mixed with 33% glucose, minerals, trace elements and vitamins provided for children a caloric intake of 49.8 +/- 17.3 Kcal/Kg/day with a nitrogen intake of 0.26 +/- 0.27 g/Kg/day. Nutritional assessment, utilizing percent ideal body weight, serum protein electrophoresis, C3, pseudocholinesterase and fibrinogen, was performed at the beginning and at the completion of each course of PN. Mean percent ideal body weight was 95.8 before PN, 98.5 on last day of PN (p less than 0.0005). Other parameters did not change significantly. No metabolic complication nor severe electrolyte imbalance were observed except for 5 patients who developed hypokalemia in coincidence with administration of Amphotericin B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Autologous bone marrow transplantation in children. Use of parenteral nutrition]. 311 38

Because of the possible involvement of cytokines in gram-negative septicemia, we investigated serum levels of tumor necrosis factor alpha, interleukin-1 beta, alpha interferon, and gamma interferon in children with gram-negative sepsis and purpura fulminans. We studied 55 patients (ages, 1 month to 19 years) with a clinical diagnosis of sepsis and purpuric lesions who were in shock or had three or more other biologic risk factors. The mortality rate was correlated with the number of risk factors present on admission to the hospital (P = 0.03). Tumor necrosis factor alpha was elevated in 91 percent of the 35 patients tested, interleukin-1 in 21 percent of the 33 patients tested, and gamma interferon in 19 percent of the 32 tested. Alpha interferon levels were within normal limits in the 32 patients tested. Serum levels of tumor necrosis factor alpha were positively correlated with the number of risk factors (P less than 0.05) and negatively correlated with blood fibrinogen levels (P = 0.01). Tumor necrosis factor alpha, interleukin-1, and gamma interferon were significantly higher in patients who died than in the survivors. Alpha interferon levels were similar in the two groups. Serum concentrations of both interleukin-1 and gamma interferon were correlated with concentrations of tumor necrosis factor alpha. These data provide evidence that serum levels of tumor necrosis factor alpha, interleukin-1, and gamma interferon correlate with the severity of meningococcemia in children. The findings may have implications for new therapeutic approaches.
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PMID:Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura. 313 97

Alpha 1-antitrypsin-Pittsburgh (AT-P), a naturally occurring lethal mutation (358Met----Arg), has been genetically engineered (rAT-P). The protein has been shown to be a potent active site-directed inhibitor of thrombin and the contact enzymes Factor XIIf, Factor XIa, and kallikrein. Because activation of the contact system is known to occur in gram-negative septicemia, the authors have hypothesized that the administration of rAT-P might modulate the course of this syndrome. Yorkshire piglets anesthetized with pentobarbital and infused with viable Pseudomonas aeruginosa (2 X 10(8) CFU) were untreated (Group I) or treated with rAT-P (Group II) and studied in a 6-hour protocol. Coagulation studies revealed that rAT-P significantly inhibited the rapid decrease in the functional concentrations of Antithrombin III, Factor XI, and fibrinogen. In addition, rAT-P markedly reduced the serum levels of fibrinogen degradation products. Survival in Group II was significantly increased during 2-5 hours but not at 6 hours when the functional levels of rAT-P in plasma were the lowest. These results indicate that this recombinant inhibitor, even at low concentrations, affords protection in experimental gram-negative septicemia.
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PMID:Recombinant alpha 1-antitrypsin Pittsburgh attenuates experimental gram-negative septicemia. 325 51

The blood coagulation system is activated regularly in severe forms of shock, polytrauma, and sepsis. Arising thrombin cleaves the fibrinopeptides A and B from fibrinogen, and it generates monomers of fibrin, which are initially kept in solution by the remaining excess fibrinogen. The effects of soluble fibrin (fibrin monomer/oligomer-fibrinogen complexes) and fibrinopeptides A and B were investigated in blood-free perfused, isolated rabbit lungs. Urea Tris buffer-dissolved fibrin monomers were injected into the pulmonary artery in the presence of circulating excess fibrinogen. In doses above 5 mg, the monomers consistently provoked a sharp rise in pulmonary artery pressure, which was followed by an elevated pressure plateau. Changing to fresh perfusate devoid of soluble fibrin did not restore the pressure to baseline, and a second administration of the soluble fibrin caused a pressor response larger than the first. Only a modest increase in lung weight (less than 2 g) was observed, and lung inflation pressure was not altered. The pressor responses were accompanied by a rapid release of thromboxane A2 and a more delayed release of prostaglandin I2 into the perfusion fluid. A significant correlation between the height of the fibrin-induced pressure rise and the amount of thromboxane release was noted. Inhibition of cyclooxygenase (indomethacin) suppressed the generation of both prostanoids, whereas inhibition of thromboxane synthetase (OKY-046 and imidazole) selectively blocked the liberation of thromboxane. All three inhibitors caused an immediate decline in pulmonary artery pressure, which had been previously elevated due to administration of soluble fibrin, and markedly reduced the pressor response evoked by a subsequent fibrin application in the same lung.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary vasoconstrictor response to soluble fibrin in isolated lungs: possible role of thromboxane generation. 334 71

Platelet consumption is a prominent feature of disseminated intravascular coagulation. We investigated whether monocyte procoagulant activity (PCA) might play a role in platelet consumption associated with gram-negative septicemia. Human mononuclear cells exposed in vitro to lipopolysaccharide demonstrated parallel dose-dependent increases in PCA and ability to induce platelet aggregation. Induction of platelet aggregation required the generation of thrombin dependent on coagulation Factors VII, X, and II, and calcium. This is consistent with monocyte tissue factor initiating thrombin generation. A specific monoclonal antimonocyte antibody was used to identify monocytes via indirect immunofluorescence, and demonstrated that all monocytes were included in platelet aggregates. Mononuclear cells that did not express PCA did not induce platelet aggregation and monocytes were not surrounded by platelet clumps. These data suggest that monocytes induced to express tissue factor on their surface may be important mediators of endotoxin-induced platelet, as well as fibrinogen, consumption.
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PMID:Human platelet aggregation is initiated by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide in vitro. 353 97

Gram-negative septic shock remains a major clinical problem. One frequently encountered complication of sepsis is disseminated intravascular coagulation (DIC). The present study was to determine in an Escherichia coli endotoxemia awake rat model the efficacy of antithrombin-III (AT-III) prophylaxis and to explore the role of DIC in the pathogenesis of endotoxemia. We demonstrated that DIC occurs very early, before the appearance of detectable serious abnormalities in cardiovascular, metabolic, and biochemical variables indicative of organ damage or dysfunction; AT-III prophylaxis significantly ameliorates DIC, as evidenced by completely preventing the fall in plasma fibrinogen concentration and significantly limiting the increases in prothrombin time and activated partial thromboplastin time after 4 hours of endotoxemia; and AT-III prophylaxis dramatically increases permanent survival. Results of this study suggest that AT-III prophylaxis is very protective above a threshold dosage in an endotoxemic rat model and that protection is in part due to ameliorating DIC. Our data also suggest that DIC occurs very early during endotoxemia and may in part be responsible for the pathogenesis of endotoxemia in the rat. We conclude that AT-III prophylaxis may be efficacious in conditions of impending DIC, such as gram-negative septicemia/endotoxemia.
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PMID:Protection against disseminated intravascular coagulation and death by antithrombin-III in the Escherichia coli endotoxemic rat. 354 29

A case of thyroid cancer causing right ventricular outflow tract obstruction is described. A 72-year-old woman was admitted because of shortness of breath, some ecchymoses, and marked anasarca. Her liver was palpable four fingerbreadths below her costal margin. Laboratory findings included leukocytosis, marked thrombocytopenia, and an increase in fibrinogen degradation products due to disseminated intravascular coagulopathy. Two-dimensional echocardiography demonstrated a solid mass in the right ventricle, which protruded into the right atrium and main pulmonary artery. Right ventricular outflow tract obstruction and tricuspid regurgitation were demonstrated by contrast echocardiography. These findings were confirmed by CT scans, RI angiography, and contrast angiography. The mass was partially resected from her right ventricle and her tricuspid valve was replaced successfully, but she died of sepsis three weeks after surgery. At autopsy, undifferentiated thyroid cancer and cardiac metastasis were verified. To date, only eight cases with initial symptoms of congestive heart failure due to right ventricular outflow tract obstruction caused by metastatic intracavitary tumors have been reported. Very rarely have cardiac tumors resulted in disseminated intravascular coagulopathy.
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PMID:[Metastatic thyroid cancer to the right ventricle causing obstruction of the right ventricular outflow tract and associated with disseminated intravascular coagulopathy: a case report]. 365 26


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