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)

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

To study the haemodynamic, cellular and humoral changes seen during septicemia-endotoxinemia a relatively large animal is needed. Pigs are satisfactory in size but have a tendency to develop malignant hyperthermia reaction to stress situations and certain anaesthetic agents. This problem was solved using a screening test of halothane exposure. When later used for experiments, the nonresponding pigs developed the typical hypokinetic low-flow state after endotoxin challenge seen in the advanced stage of septicemia in man. Decreased number of circulating leucocytes and platelets, increased tissue thromboplastin production in monocytes, and a significant coagulation disorder (DIC) were observed. Release of oxygen radicals and lysosomal enzymes from leucocytes could be estimated. Endotoxin levels in plasma were easily measured. This pig model of controlled endotoxinemia correlates well with some important haemodynamic, cellular and humoral reactions observed during human in vivo observations and in vitro studies. This model may thus be a valuable tool in clinical research of endotoxinemia and septicemia.
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PMID:Controlled endotoxinemia in pigs. A suitable model for in vivo studies of some haemodynamic, humoral and cellular reactions. 653 28

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

Thrombocytopenia is characteristically associated with septicemia and hemolytic uremic syndrome (HUS), a subset of which has been shown to be associated with endotoxemia and shigellosis. An experimental model that closely resembles these clinical conditions is the generalized Shwartzman reaction modified with a continuous intravenous infusion of endotoxin for 5 hr in rabbits. In addition to exhibiting the triad of HUS (thrombocytopenia, hemolytic anemia, and azotemia), these animals also had circulating platelet aggregates, leukocytosis, lipidemia, hemoglobinemia, hyperfibrinogenemia, and prolonged partial thromboplastin time. Platelets that remained in circulation were chemically exhausted in serotonin content and functionally impaired in aggregation activities. Plasma from animals during thrombocytopenia and platelet functional deficiency had no effect of the aggregation responses of normal platelets. Although the single triggering event of endotoxin infusion was stopped at hour 5, recovery from abnormalities was only partial on day 2 and within normal limits by day 3. In vitro studies supported platelet exhaustion as a mechanism for decreased platelet function after endotoxin infusion. The presence of circulating platelet aggregates and exhausted platelets suggested that the process of platelet activation took place at as long as 24 hr after the cessation of LPS infusion. Endotoxin and other mechanism(s) are likely to be operative in the pathogenesis leading to platelet activation. Further studies to reveal the mechanism of platelet exhaustion in the experimental model may help our understanding of corresponding events in clinical endotoxic injury and HUS associated with endotoxemia.
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PMID:Impaired and exhausted platelets in modified generalized Shwartzman reaction: an analogue of hemolytic uremic syndrome associated with endotoxemia. 664 55

The potential contribution of Kupffer's cells, le, hepatic macrophages (HM phi s) to the diffuse microvascular thrombosis seen during septicemia was evaluated by measuring the ability of a homogeneous population of explanted HM psi s to express procoagulant activity (PCA). Addition of as little as 100 ng/mL of endotoxin stimulated a 30-fold increase over control values of PCA within eight hours. This PCA was membrane associated and functioned externally to the macrophage. Sensitivity to heat (56 degrees C) and diisopropyl fluorophosphate differentiated this PCA from typical tissue thromboplastin activity. The increase in PCA was blocked by pretreatment with warfarin sodium (a phytonadione blocker) and could be restored by addition of phytonadione. These studies showed that endotoxin induces in HM psi s a significant increase in PCA, functioning like coagulation factor VII. These results support a role for Kupffer's cells in the initiation of microvascular thrombosis in endotoxemia.
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PMID:Potential for endotoxin-activated Kupffer's cells to induce microvascular thrombosis. 668 75

Coagulation studies were performed on 16 children with gram-negative septicemia without the complications of septic shock, liver disease, malnutrition, or laboratory evidence of classic disseminated intravascular coagulation (DIC). Ten (63%) of the 16 cases were found to have abnormal partial thromboplastin and/or prothrombin times. The coagulopathy was caused by a reduction in the vitamin K-dependent coagulation factors. The mechanism that produced this coagulopathy was not known, but evidence was found that suggested that endotoxin may interfere with the vitamin K-carboxylation reaction. The data indicated that abnormal coagulation screening test results in children with gram-negative septicemia were not specific for DIC and that a significant number of patients had a coagulopathy not related to DIC.
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PMID:Vitamin K-dependent coagulation factors in gram-negative septicemia. 670 67

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

Goats, sheep and calves were inoculated intravenously with strain Y3343 of the large colony type of Mycoplasma mycoides subsp. mycoides isolated from a goat with polyarthritis. The goats and sheep died of septicemia (one was killed in extremis) within eight days. The goats had leukopenia and granulocytopenia. Coagulopathy was indicated in some goats; the fibrinogen titer, prothrombin and partial thromboplastin times increased with the progress of disease and the number of platelets decreased dramatically in one goat. Goats and sheep had cellulitis at the site of inoculation, pleural hemorrhages, pneumonia, myocarditis, renal infarcts, glomerulitis, adrenal cortical necrosis, enteritis, focal splenic necrosis, polyarthritis and lymphadenitis. Vasculitis and thrombi were seen occasionally, suggesting that vascular changes, perhaps together with coagulopathy, had a role in pathogenesis. One of two experimental calves developed a slight fever, arthritis and minor inflammation of adrenal tissue. Calves seen less susceptible to the mycoplasma organism given intravenously than do goats or sheep.
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PMID:Experimental infection of goats, sheep and calves with the large colony type of Mycoplasma mycoides subsp. mycoides. 700 31

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


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