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)

Central venous plasma concentrations of thromboxane B2 (TXB2) the stable metabolite of the vasoconstrictor platelet aggregator thromboxane A2, were measured in 12 patients with septic shock. In 8 patients dying with septic shock the concentration of plasma TXB2 (912 +/- 250 pg/ml) was ten times higher than that in 4 survivors of septic shock (92 +/- 25 pg/ml) and 6 controls (91 +/- 18 pg/ml). Prothrombin time and partial thromboplastin time were significantly prolonged in nonsurvivors compared with survivors. Similarly, the alveolar-arterial oxygen gradient was significantly raised in nonsurvivors (233 +/- 39 mm Hg) compared with survivors (112 +/- 47 mm Hg). This study demonstrates that the metabolism of arachidonic acid to thromboxanes is increased in patients dying of septic shock and this raises the possibility that thromboxanes may be involved in the disseminated intravascular coagulation and respiratory distress syndrome associated with severe sepsis.
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PMID:Plasma thromboxane concentrations are raised in patients dying with septic shock. 612 85

Measurements of the heparin level were made under continuous anticoagulation in a total of 7 patients. For the purpose of monitoring heparin the coagulation time values were determined parallelly. Except a patient with a sepsis and a 7 days old newborn baby the desired prolongation for the partial thromboplastin time and the reaction time of thrombelastogram resulted from heparin titres lying within the range of 0.2-0.7 U/ml of plasma. Even after applying depot preparations there was a relatively good correspondance of heparin level curves and coagulation parameters. In childhood the partial thromboplastin time is primarily suitable for monitoring the heparin therapy. Heparin half-life times calculated during the transumbilical exchange transfusion in 7 children amounted to values ranging between 40-110 minutes. In addition to checking low dose heparinizing, measurements of the level are suitable for deriving dosage standards for neutralizing heparin effects by protamine sulfate.
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PMID:[Heparin and antiheparin in childhood. 3. Heparin level measurements and their importance in heparin monitoring]. 619 49

Sixty-seven patients were treated with moxalactam in a noncomparative trial of hospitalized patients; 32 had endometritis or chorioamnionitis, 12 had skin and soft tissue infections, 5 had osteomyelitis, 5 had pneumonia, 5 had urinary tract infections, 4 had arthritis, 2 had sepsis from an unknown source, 1 had endocarditis, and 1 had peritonitis. Bacteremia was present in 12 of these patients. Patients were given 3 to 12 g of moxalactam per day (mean, 6.24 g/day) in divided doses every 6 to 8 h. Seven patients were given intramuscular treatment for 3 to 20 days for part or all of their therapy. The rest were given intravenous treatment exclusively. Treatment was continued for 2 to 42 days (mean, 10 days). The dose and the duration of therapy were determined by the type of infection and the response of each patient. There were four treatment failures and one enterococcal-clostridial superinfection. Moxalactam was well tolerated. Allergic reactions led to the discontinuation of the antibiotic in three patients. Prolonged prothrombin and partial thromboplastin times were observed in 2 of 11 patients tested; in both instances in patients had severe underlying diseases, including malnutrition and alcoholism. Pain on intramuscular injection was noted in two patients receiving 1,500 mg, but not in five receiving a lower dose; in one case the pain forced the use of intravenous therapy after one dose, and in the other case the pain was mild and the patient was treated for 20 days. We concluded that moxalactam was effective in the treatment of the types of infections included in this study and produced few adverse reactions.
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PMID:Moxalactam in the therapy of serious infections. 621 Nov 40

The purpose of this study has been to provide information on the mortality and morbidity rates for operation on nonbleeding cirrhotic patients and to identify factors that portend a grave prognosis. A review of 102 cirrhotic patients who underwent a variety of major therapeutic operations revealed a mortality rate of 19.6 percent. Mortality rates were significantly increased (p less than 0.05) by emergency operation (45.8 percent), gastrointestinal related operation (27.6 percent), ascites (37.5 percent), a bilirubin concentration greater than 3.5 mg (44.4 percent), a prothrombin time increase greater than 2 seconds (36.1 percent), a partial thromboplastin time increase greater than 2 seconds (50 percent), an alkaline phosphatase concentration greater than 70 units (40.9 percent), an operative blood loss greater than 1,000 ml (33.3 percent), and the presence of one or more postoperative complications (39.6 percent). Mortality rates were not increased after extremity, genitourinary, or gynecologic operations, an albumin concentration less than 3 g, a serum glutamic oxalacetic transaminase concentration greater than 40 units, hepatomegaly, and a history of previous gastrointestinal bleeding. When significant risk factors were added, mortality rates were significantly associated (p less than 0.001): zero to one factors 5.1 percent, two to three factors 19.4 percent, four to five factors 33.3 percent, and more than six factors 66.7 percent. The complication rate was 47.1 percent and included liver failure (42.2 percent), sepsis (18.6 percent), and bleeding (8.8 percent). Thus, in cirrhotic patients a clear need for operation must exist, liver function must be optimized preoperatively, and the most simple and expeditious procedure must be performed to avoid excessive blood loss and postoperative complications.
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PMID:Morbidity and mortality after operation in nonbleeding cirrhotic patients. 660 65

Disseminated intravascular coagulation (DIC) was diagnosed as a secondary disease in 6 horses. Four horses had localized and/or systemic sepsis, one horse had disseminated neoplasia, and one had idiopathic ulcerative enteropathy. The diagnosis of DIC was based on the finding of at least 3 of 4 abnormalities: thrombocytopenia, prolonged prothrombin time, prolonged activated partial thromboplastin time, and a high concentration of fibrinolytic degradation products. The most common clinical signs other than those attributable to the primary disease process were abnormal hemorrhage (4 hours) and venous thrombosis (4 horses). All horses eventually died or were euthanatized because of the severity of the primary disease.
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PMID:Disseminated intravascular coagulation in six horses. 664 11

These studies were undertaken to determine the type and availability of the procoagulant activities generated in blood incubated with endotoxin. The shortening of the recalcification time of blood incubated with endotoxin was directly correlated with the increase in synthesis of tissue thromboplastin in the monocytes. The procoagulant activity which resulted in the shortening of the clotting time was shown to be almost totally blocked by tissue thromboplastin antibodies. Thus, no additional procoagulant activity was generated in platelets during the 5 h incubation of blood with endotoxin. However, lysed platelets enhanced the synthesis of tissue thromboplastin in blood monocytes in the presence of endotoxin. Lysed red blood cells or granulocytes had no such effect. In endotoxin stimulated monocytes the main part of the newly synthesized tissue thromboplastin appeared to be exposed on the cellular surface. Thus, only 25% of the tissue thromboplastin activity was recovered when tissue thromboplastin antibodies had been present during the stimulation. Unstimulated monocytes were also found to possess tissue thromboplastin activity, but this low activity was not affected by tissue thromboplastin antibodies unless the monocytes were disrupted by sonication. The high percentage of tissue thromboplastin exposed on the surface of the endotoxin stimulated monocytes in whole blood may contribute significantly to the rapid induction of disseminated intravascular coagulation in gram negative sepsis.
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PMID:The production and availability of tissue thromboplastin in cellular populations of whole blood exposed to various concentrations of endotoxin. An assay for detection of endotoxin. 681 61

Disseminated intravascular coagulation (DIC) is a common occurrence during clinical sepsis and can be induced in the experimental host by LPS. Fibrin deposition in the hepatic microcirculation has been observed within 30 min of i.v. injection of LPS. Because mononuclear phagocytes have been shown to produce a PCA after exposure to LPS, we have examined the ability of a homogeneous population of explanted hepatic macrophages to express PCA. Addition of as little as 10 ng/ml of LPS stimulated a 15- to 20-fold increase in PCA over control culture levels within 7 1/2 hr post-treatment. The PCA was found to be membrane-associated, with approximately 90 to 95% of the total PCA present in the cellular lysates, and more than 85% was inhibited by pretreatment of the cells with the diazonium salt of sulfanilic acid, an inhibitor of ecto-enzymes. In contrast to tissue thromboplastin produced by other M phi populations, the H-M phi PCA was found to be markedly sensitive both to heat inactivation at 56 degrees C and to inhibition by 1 mM DFP. Additionally, assays involving both a 1-stage coagulation test as well as an enzyme assay with a Factor Xa-specific substrate (using normal and deficient human plasmas) demonstrated that the H-M phi PCA appears to activate Factor X directly. Unlike tissue thromboplastin, the H-M phi PCA is non-dependent of Factor VII activation. These studies: 1) demonstrate the LPS induces a unique PCA in the H-M phi, and 2) support a role for the H-M phi in the initiation of DIC in endotoxemic shock.
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PMID:The induction of a unique procoagulant activity in rabbit hepatic macrophages by bacterial lipopolysaccharides. 702 10

An analysis was made of 41 cases of disseminated intravascular coagulation in dogs, with the objective of evaluating routine and nonroutine laboratory tests used in making the diagnosis. The dogs were grouped on the basis of underlying disease, which included neoplasia (39%), pancreatitis (30%), chronic active hepatitis (15%), heat stroke (12%), and sepsis (4%). Of the diagnostic tests evaluated, those for determination of activated partial thromboplastin time, antithrombin III activity, prothrombin time, and the platelet count were the most valuable. Of the clotting factors, factor V activity was decreased more frequently than the activity of factor VIII:C (factor VIII: procoagulant). The factor VIII:C activity was in conflict with prevailing dogma that reflects depression of this factor in disseminated intravascular coagulation. Factor VIII:C activity was decreased in only 29% of dogs studied. Activation of the fibrinolytic system was manifested by decreased plasminogen activity in 49% of the dogs studied. Sixty-one percent of the dogs had increased amounts of fibrin (ogen) degradation products.
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PMID:Disseminated intravascular coagulation: antithrombin, plasminogen, and coagulation abnormalities in 41 dogs. 726 67

Acute respiratory failure is a common complication in patients with disseminated intravascular coagulation associated with sepsis. To elucidate the role of coagulation abnormalities in acute lung injury in sepsis, we investigated the effect of anticoagulants on the pulmonary vascular injury in rat induced by lipopolysaccharide (LPS). When administered intravenously, LPS (5 mg/kg body weight) significantly increased the accumulation of 111indium-labeled neutrophils in lung 30 min after administration. Subsequently, the pulmonary vascular permeability and the serum level of fibrin and fibrinogen degradation products (E) [FDP (E)] increased and remained elevated for several hours. Neither heparin alone, heparin plus antithrombin III, or dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa, a selective inhibitor of thrombin generation, prevented LPS-induced vascular injury 6 hours after LPS administration, whereas these substances significantly inhibited the increase in serum FDP (E) at that time. LPS-induced pulmonary vascular injury was significantly attenuated in rats with methotrexate-induced leukocytopenia or treated with ONO-5046, a potent granulocyte elastase inhibitor, although ONO-5046 did not inhibit the LPS-induced increase in serum FDP (E). Thus, activated leukocytes play a more important role than coagulation abnormalities in the pathogenesis of LPS-induced pulmonary vascular injury in an experimental rat model of endotoxemia.
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PMID:Endotoxin-induced pulmonary vascular injury is mainly mediated by activated neutrophils in rats. 748 29

Endotoxin(lipopolysaccharide = LPS), cell wall component of gram-negative bacteria, activates monocytes and macrophages to release cytokines, reactive nitrogen intermediates (RNI), and to generate tissue factor(TF) which initiate coagulation. We have purified 7kDa and 18kDa cationic antibacterial proteins (CAP-7 and CAP-18) with LPS-binding and LPS-neutralizing activities from rabbit granulocytes using as an assay the agglutination of erythrocytes coated with Re-LPS. From protein sequencing, CAP-7 was identified as the C-terminal 37 amino acid fragment of CAP-18. Synthetic peptide #197 (identical sequence to CAP-7, Gly1-Try37) and #36-1 (a truncation of CAP consisting of 32 amino acid residues, Gly1-Ala32) showed LPS-binding activity. Each peptide inhibited LPS-induced tissue factor(TF) generation by murine peritoneal macrophages, even added 1-3 hours after stimulation of cells with LPS. C57BL/6 mice treated with #197 were significantly protected from lethal LPS challenge. Peptide #36 also blocked the LPS-induced lethality. These peptides had antibacterial activity to gram-negative bacteria, such as E.coli, S.typhimurium, K.pneumonia, Ps.aeruginosa and also to gram-positive S.aureus (Methicillin sensitive and resistant strains). Both peptides inhibited TF- and Xa-induced plasma clotting. Using synthetic chromotogenic substrates, both CAP7 peptides blocked the coagulation cascade at two sites, activation of factor X to Xa and conversion of Factor II (prothrombin) to factor IIa (thrombin). In vivo treatment of peptide #197 prevented acute lethality in mice injected with tissue factor (rabbit brain thromboplastin). Two other peptides, #32(Gly1-Phe9) and #50(Ile13-Typ37) failed to demonstrate LPS-binding, LPS-neutralizing, antibacterial and anticoagulant activities. The active peptides but not the inactive peptide maintain a putative heparin binding domain at their N-termini. This heparin binding domain is participate in the LPS-binding, LPS neutralizing, antibacterial and anticoagulant activities of CAP7. These active peptides may have a therapeutic potential for treatment for DIC due to sepsis and endotoxin shock.
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PMID:Endotoxin-binding synthetic peptides with endotoxin-neutralizing, antibacterial and anticoagulant activities. 783 55


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