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)

To evaluate the availability of the fibrinolytic system in patients suffering from acute respiratory distress syndrome, ARDS, induced by septicemia or trauma, the following parameters were analysed: fibrinogen, FG, antithrombin III, AT III, plasma prekallikrein, PPK, plasminogen, PG, alpha 2-antiplasmin, alpha 2-AP, alpha 2-macroglobulin, alpha 2-MG, urokinase-inhibitor, UK-I, streptokinase-inhibitor, SK-I, C1-inhibitor, C1-I, alpha 1-antitrypsin, alpha 1-AT, and fibrinogen-fibrin degradation products, FDP. Survivors and non-survivors of septicemia induced ARDS showed a characteristic feature: marked increase of FG and pronounced decrease of AT III and PPK in the coagulation system; concerning the fibrinolytic system a decrease of PG, alpha 2-AP and alpha 2-MG as well as an increase of inhibitors of PG-activators (PG-antiactivators) UK-I, SK-I, C1-I and alpha 1-AT; the FDP-titer was elevated. This constellation of parameters is interpreted as indicative of a marked procoagulant stimulation rendering the organism a state of hypercoagulability coinciding with a diminished availability of the fibrinolytic system, due to exhaustion of the fibrinolytic potential and increase of PG-antiactivators. In the trauma group initially the rise of FG, SK-I, C1-I and alpha 1-AT is absent independent of the outcome, but develops with progression of the disease. As ARDS is more frequently associated with septicemia, diminished availability of the fibrinolytic system simultaneously with increased procoagulant stimulation may be a particular pathophysiologic mechanism in the pathogenesis of ARDS.
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PMID:Fibrinolysis inhibition in acute respiratory distress syndrome. 386 24

Endotoxin producing bacteria cause disseminated intravascular coagulation (DIC); however, the mechanism of endotoxin action in man is still unclear. Impairment of the fibrinolytic system has been suggested as a contributing mechanism. A single injection of Escherichia coli lipopolysaccharide in rabbits resulted in a marked and prolonged increase of the levels of a fast-acting inhibitor of plasminogen activator (PA-inhibitor) in plasma (from 3.9 +/- 0.7 to 41 +/- 13.2 U/ml after 3 h). Gel filtration studies indicated that inhibition of human tissue-type plasminogen activator (t-PA) by rabbit plasma is accompanied by a change in the elution profile of the activator compatible with the formation of an enzyme-inhibitor complex with an apparent molecular weight of 100,000. Injection of human t-PA (1,500 IU/kg body wt) in endotoxin treated animals resulted in very fast inhibition of t-PA and formation of a similar complex. The half-life of circulating PA-inhibitor activity in rabbits was about 7 min as estimated by donor receiver plasma transfusion experiments. Stimulation of cultured human endothelial cells with endotoxin resulted in enhanced rate of accumulation of PA-inhibitor activity in the culture medium (two- to sevenfold increase). In five patients with septicemia, markedly increased levels of PA-inhibitor (14.3 +/- 15.5 U/ml) as compared with control subjects (1.3 +/- 0.7 U/ml) were observed in plasma. A very strong correlation (r = 0.98) was found between inhibition of t-PA and of urokinase in all conditions, suggesting that this fast-acting inhibitor reacts with both plasminogen activators. These data suggest that the appearance of this fast-acting PA-inhibitor is very sensitive to endotoxin stimulation. The marked increase in the level of PA-inhibitor in blood may contribute to the pathogenesis of DIC in septicemia.
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PMID:Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. 392 Feb 45

Plasma fibronectin (PFN) depletion has been associated with poor outcome in patients with sepsis or those who have experienced trauma; restoration of normal levels appears beneficial. PFN synthesis is increased after cecal ligation even in malnourished animals with sepsis, implying that stimulation of endogenous PFN synthesis is possible. One hundred rats received either a single therapeutic agent (gelatin, heparin, indomethacin, urokinase, captopril, or endotoxin) or the combination of a cecal ligation and a single agent (cimetidine, methylprednisolone, epsilon-aminocaproic acid (EACA), or transaminomethyl cyclohexane carboxylic acid. PFN levels were measured by enzyme-linked immunosorbent assay at 0, 24, and 48 hours. Only endotoxin alone caused significant PFN elevation at 24 to 48 hours (p less than 0.01); however, its multiplicity of effects precludes localization of regulatory pathways. Methylprednisolone results in an accelerated rise in PFN levels after operation (p less than 0.05), probably through an intracellular augmentation PFN synthesis. EACA attenuates the postoperative response while transaminomethyl cyclohexane carboxylic acid augments the PFN rise. This effect of EACA implies the existence of a proteolytic fragment capable of stimulating PFN synthesis. If a nontoxic factor can be identified, the use of exogenous PFN may be avoided.
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PMID:Modulators of plasma fibronectin response during sepsis. 637 57

Hemodialysis is an important component of chronic renal replacement therapy, which is increasingly being provided with indwelling venous catheters. Catheter malfunction is commonly dealt with using Urokinase instillation or endovascular catheter stripping. We describe the application of a simple technique that allows the indwelling dialysis catheter to be replaced in a subcutaneous tunnel following manipulation for flow problems. Function was restored in all catheters without occurrence of tunnel infection or catheter-related sepsis. Preliminary results offer evidence of the efficacy of the technique in salvaging dialysis catheters, especially in patients with difficult vascular access.
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PMID:Method of salvaging long-term dialysis catheters. 748 14

Vascular catheter-related infection is an important cause of mortality and morbidity in hospitalized patients. The mean incidence of catheter-related bloodstream infection in hospitalized pediatric patients is 2.4 episodes per 1,000 days. Totally implantable central venous catheters may be associated with a lower risk of infection. Coagulase-negative staphylococci are the predominant cause and account for about one third of episodes of catheter-related bloodstream infection. The diagnosis of catheter-related bloodstream infection is often difficult because there are frequently no signs of inflammation around the catheter. Diagnosis depends on either a positive quantitative catheter culture yielding the same microorganism recovered from the bloodstream or differential quantitative blood cultures with significantly greater colony counts from blood drawn through the catheter than from blood drawn through a peripheral vein. Alternatively, probably catheter-related sepsis can be diagnosed when clinical sepsis is refractory to antimicrobial therapy but responds to catheter removal. Often these criteria are not met but catheter-related bloodstream infection is presumed because a common skin microorganism is isolated from the blood when clinical manifestations of bloodstream infection are present and there is no other apparent source of infection. Microorganisms causing catheter-related bloodstream infection gain access to the bloodstream predominantly from either the catheter insertion site or the catheter hub. Most catheter-related infections occurring shortly after catheter insertion probably gain access to the bloodstream by extraluminal migration along the catheter from the skin at the catheter insertion site. When catheters are in place for extended periods, especially greater than 30 days, the catheter hub probably plays a major role in microorganisms gaining access and then migrating endoluminally until reaching the bloodstream. Recently employed strategies for the prevention of catheter-related infections include topical antibiotics or antiseptics at the catheter insertion site, flush solutions containing vancomycin, and bonding antimicrobial agents to the catheter. Infection of peripheral and central venous catheters generally resolves after catheter removal. For tunneled silicone catheters, most episodes of catheter-related infection can be initially managed with antimicrobial therapy infused through the catheter without catheter removal. Staphylococcus aureus is generally more aggressive and associated with more complications than coagulase-negative staphylococci. Microorganisms that usually require catheter removal include Candida and Bacillus species. Adjunctive treatments of catheter infections include the use of urokinase. Catheter-related infection remains an important complication of vascular access. Novel prevention and treatment strategies are currently being investigated. In the near future bonding of antibiotics or other agents to catheters may become routine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intravenous catheter-related infections. 771 11

Reliable access to a central vein is increasingly important in the treatment of major acute and chronic disease. The use of an implantable central venous access device in a district general hospital is reviewed. Fifty-four PortaCaths (Kabi Pharmacia, Milton Keynes, UK) were inserted in 51 patients over a 7-year period. Most patients had haematological disease, often with neutropenia and thrombocytopenia. There were a total of 22,515 catheter days experience. Twelve catheters were removed for complications with an overall complication rate of 0.93/1000 catheter days. There were four line infections and four episodes of periport sepsis. Occasional catheter thrombosis was usually cleared with urokinase. Neutropenic and immunocompromised patients had an increased complication rate. PortaCaths were well tolerated by patients and required minimum maintenance. An implantable central venous access device proved safe and reliable for use in a district general hospital.
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PMID:Experience of an implantable central venous access system in a district general hospital. 773 94

The receptor for urokinase plasminogen activator (uPA-R, CD87) is a glycosylphosphatidylinositol (GPI)-anchored 50 to 65 kD glycoprotein that, by regulating membrane-associated plasmin activity, may facilitate the invasion of inflammatory and malignant cells. Certain other GPI-anchored glycoproteins are shed from the cell membrane and exist as soluble products in vitro and in vivo. To determine if uPA-R undergoes a similar phenomenon, we have developed a sensitive enzyme-linked immunoabsorbent assay (ELISA) (using a rabbit antiserum as both capture and detection reagents) to measure the quantity of soluble uPA-R (suPA-R) in tissue culture supernatants and biologic fluids. Using this ELISA, we have detected suPA-R in the culture supernatants of U-937 cells and human monocytes stimulated in vitro by certain soluble inflammatory mediators (Sitrin et al, Blood 84:1268, 1994; Mizukami et al., Clin Res 42:115A, 1994). To determine if suPA-R exists in vivo, we have screened the plasma of 20 normal volunteers (mean +/- SD, 3 +/- 3 ng/mL; median, 2 ng/mL; range, 1 to 11 ng/mL [serum values slightly higher]); the plasma of 13 ICU patients with clinical sepsis syndrome (mean +/- SD, 30 +/- 11 ng/mL; median, 11 ng/mL; range, 4 to 221 ng/mL); and the extravascular fluids (pleural, pericardial, and peritoneal) of 84 individuals with presumed inflammatory or malignant conditions (mean +/- SD, 21 +/- 39 ng/mL; median, 10 ng/mL; range, 2 to 253 ng/mL). Among the latter specimens, most were inflammatory exudates (only six were malignant by positive cytology) with the highest quantities of suPA-R associated with neutrophilic exudates. The solubility of suPA-R contained within these fluids was confirmed by reanalysis after ultracentrifugation to remove particulate material. When tested in a uPA ligand capture ELISA, representative specimens of extravascular body fluids and sepsis plasma contained suPA-R capable of binding uPA ligand (generally representing a small fraction of the immunoreactive material). We conclude from these data that suPA-R is immunologically detectable in vitro and in vivo with high concentrations of receptor found under conditions of inflammatory stimulation. The possibility of suPA-R's biologic activity is suggested by its partial retention of ligand binding capacity.
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PMID:Enzyme-linked immunoabsorbent assay detection of a soluble form of urokinase plasminogen activator receptor in vivo. 779 25

The vascular endothelium plays a central role in the regulation of extrinsic fibrinolysis and thus maintains vascular patency through clot dissolution. Plasminogen activation provides an important source of localized proteolytic activity not only during fibrinolysis but also during a variety of other physiological and pathological processes. Numerous studies have indicated that human endothelial cells can directly synthesize and secrete plasminogen activators (PA) and inhibitors of these activators. PAs specifically hydrolyse a single arginine-valine bond in plasminogen, an abundant and widely distributed plasma zymogen, to form the broad spectrum serine protease, plasmin. Tissue type-PA (t-PA) and urokinase type PA (u-PA) forms of PA have been described in endothelial cells, although t-PA production and secretion is elevated most frequently. The tPA form of PA functions predominantly in endothelial cell mediated fibrinolysis, while uPA is involved in tissue remodeling. During inflammatory reactions activated mononuclear phagocytes produce a variety of cytokines which may influence the phenotype of the endothelium through a process termed "endothelial cell activation". Tumor necrosis factor alpha (TNF alpha), a mononuclear cytokine, is a distinct polypeptide of Mr 17,000 and has been implicated as a mediator of gram negative induced sepsis as well as angiogenesis. TNF alpha is known to interact with specific endothelial cell receptors and to alter endothelial coagulant and anticoagulant properties implying that cytokines may be potent modulators of hemostasis. Recent observations have indicated that TNF alpha and lymphotoxin (TNF beta) can promote the expression, synthesis and secretion of urokinase plasminogen activator (uPA) in human endothelial cells. The upregulation of uPA results in an alteration in the fibrinolytic capacity of endothelial cells and allows cells the selective ability to degrade and invade underlying subendothelial extracellular matrix (ECM). Endothelial cells treated with TNF alpha also display, in an in vitro angiogenic assay, the ability to invade Matrigel and reorganize into tube-like structures, unlike control cultures. The effects of TNF alpha on the PA proteolytic system of endothelial cells, the biological significance of this event and potential in vivo consequences will be discussed. In addition, the influence of cytokine regulatory control systems will be described, since it is becoming increasingly clear that cytokines do not act in isolation. The vascular endothelium serves as a widely distributed anatomical interface between the blood and tissue with diverse capabilities, performing distinctive biologic functions at different sites and within specific organs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytokine regulation of endothelial cell extracellular proteolysis. 835 23

Use of right atrial catheters (RACs) in children with cancer improves the comfort and efficacy of therapy. However, catheter-related infections are responsible for significant morbidity leading to the removal of approximately 20% of implanted RACs. Sepsis has been linked to thrombus and fibrin sheath formation within the RAC. Gram-negative and fungal infections appear to be particularly resistant to antibiotic therapy alone and most of these infections have required catheter removal. Urokinase has been effectively used for reopening thrombus occluded RACs. Theoretically, thrombolytic agents could improve the treatment of catheter-related infections by removing luminal sites of bacterial/fungal colonization. We prospectively monitored the use of urokinase and antibiotics for catheter-related sepsis in our pediatric hematology/oncology population from 1985 to 1991. Sepsis episodes were treated with 2 doses of urokinase and antibiotics (10 to 42 days) infused through the RAC. One to 2 mL of urokinase (5,000 U/mL) was instilled in the RAC for 1 hour, then removed and repeated 24 hours later. During the study, 224 RACs were placed in 177 children. RACs were in place for a total of 71,134 days (median, 274 days). There were 67 blood culture-positive sepsis episodes occurring in 50 RACs. Fifty-nine sepsis episodes were treated with urokinase and antibiotics and all responded by clearance of organisms from the blood. Three patients (5.1% of urokinase treated) had recurrent sepsis with the same organism within 2 months, were considered treatment failures and had RACs removed. Only 1 of 16 episodes of multiple organism/Candida sepsis led to RAC removal due to inability to cure the infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prospective analysis of urokinase in the treatment of catheter sepsis in pediatric hematology-oncology patients. 846 45

We report a case of iliac stent infection. Nine days after a 24-hour infusion of urokinase and right iliac artery stent deployment, the patient had fever, in addition to severe groin pain and petechiae isolated to the stented limb. The hospital course was complicated by sepsis, adult respiratory distress syndrome, liver dysfunction, and renal insufficiency. Stent removal and iliac/femoral artery resection, as well as an above-knee amputation, were life-saving. Arterial and stent cultures grew Staphylococcus aureus. Stent infection with arterial necrosis is a devastating, rare endovascular complication. Given its potential seriousness, we would recommend the use of prophylactic antibiotics before stent deployment.
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PMID:Endovascular stent infection. 860 99


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