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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrin degradation products (FDP) D and E, total protein, cell count, and alpha-1-antitrypsin levels have been measured in the cerebrospinal fluid (CSF), and FDP-D and E, and alpha-1-antitrypsin analyzed in serum in 13 cases of meningococcal disease, six with meningococcal septicemia and seven with meningitis. Neisseria meningitidis serotype B was the responsible agent in all cases. The following conclusions are obtained: 1) The presence of FDP in the CSF has no prognostic value, and its detection only in plasma does not exclude a fatal outcome. 2) Statistical analysis of the data suggests that the presence of FDP in the CSF is not the result of passive transfer from plasma but it indicates a meningeal inflammatory reaction. 3) Alpha-1-antitrypsin levels are elevated in meningococcal infections both in plasma and in the CSF, and they significantly correlate with the intensity of the fibrinolytic activity.
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PMID:[Fibrin-fibrinogen degradation products in cerebrospinal fluid of patients with meningococcal infections (author's transl)]. 744 35

Various assays have been developed for quantitation of soluble fibrin or fibrin monomer in clinical plasma samples, since this parameter directly reflects in vivo thrombin action on fibrinogen. Using plasma samples from healthy blood donors, patients with cerebral ischemic insult, patients with septicemia, and patients with venous thrombosis, we compared two immunologic tests using monoclonal antibodies against fibrin-specific neo-epitopes, and two functional tests based on the cofactor activity of soluble fibrin complexes in tPA-induced plasminogen activation. Test A (Enzymun-Test FM) showed the best discriminating power among normal range and pathological samples. Test B (Fibrinostika soluble fibrin) clearly separated normal range from pathological samples, but failed to discriminate among samples from patients with low grade coagulation activation in septicemia, and massive activation in venous thrombosis. Functional test C (Fibrin monomer test Behring) displayed good discriminating power between normal and pathological range samples, and correlated with test A (r = 0.61), whereas assay D (Coa-Set Fibrin monomer) showed little discriminating power at values below 10 micrograms/ml and little correlation with other assays. Standardization of assays will require further characterization of analytes detected.
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PMID:Comparison of immunological and functional assays for measurement of soluble fibrin. 858 5

An animal model of gram-positive septicemia was developed to evaluate the effects of antithrombin (AT) concentrates on morbidity, mortality, and laboratory consequences of disseminated intravascular coagulation (DIC). DIC was induced in guinea pigs by infusing Staphylococcus aureus (SA) isolated from blood cultures of patients with DIC (DIC-SA) or without DIC (non-DIC-SA). The non-DIC-SA animals and animals infused with sterile saline served as controls. Varying doses of AT were administered either 30 minutes or 24 hours after infusion of SA. DIC was confirmed within 4 hours by changes in prothrombin time, activated partial thromboplastin time, fibrinogen, fibrinogen-fibrin degradation products, and AT activity. Clinical bleeding was also evident. Mortality of untreated DIC-SA animals was 36% within 24 hours and up to 75% by 72 hours. Intervention with any dose of AT between 125 and 1,000 IU/kg 30 minutes after DIC-SA infusion was associated with 100% survival (P < or = .05 in the 250 IU/kg group) and sustained increases in AT activity and fibrinogen concentrations (P < or = .05). When AT was administered in combination with low molecular weight heparin (LMWH) or if LMWH was adminstered alone, mortality from DIC-SA was slightly, but not significantly reduced compared with untreated DIC-SA. Gross hemorrhage was observed premortem and at autopsy in all of the DIC-SA animals but in substantially fewer animals that received AT (P < or = .001 in the 250, 500, and 1,000 IU/kg groups). In contrast, groups treated with LMWH, alone or with AT, experienced hemorrhage and appeared to develop pathologic DIC. Fibrin formation in end-organs was detected in all guinea pigs in the untreated DIC-SA group and in the groups treated with 125 IU/kg AT and LMWH alone. AT doses between 250 and 1,000 IU/kg administered 30 minutes after DIC-SA infusion prevented fibrin formation in end-organs (P < or = .001 in the 250 and 1,000 IU/kg groups). AT administered 24 hours after DIC-SA could not reverse pre-existing histopathologic evidence of DIC but favorably affected survival, which reached statistical significance in the 1,000 IU/kg AT group (P < or = .025). In summary, suprapharmacologic doses of AT concentrate significantly decreased morbidity and mortality and ameliorated adverse changes in laboratory measures induced by DIC-SA in this guinea pig model and were not associated with untoward hemorrhagic complications. These findings provide justification for studying the use of AT therapy in patients with DIC-SA.
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PMID:The suprapharmacologic dosing of antithrombin concentrate for Staphylococcus aureus-induced disseminated intravascular coagulation in guinea pigs: substantial reduction in mortality and morbidity. 919 63

The addition of antibiotics to an adhesive haemostat results in an ideal system for the treatment of a localized infectious disease. Fibrin sealant (FS) is a biocompatible, resorbable, adherent haemostat that can deliver antibiotics. Previous use of fibrin to deliver antibiotics resulted in rapid release and limited bioactivity. We have reported previously that poorly soluble antibiotics significantly retard release from FS, resulting in extended delivery in vitro, and overcome antibiotic-resistant infection. We now report that localized antibiotic delivery from FS controls peritoneal infection without measurable systemic antibiotic. Rats and mice were implanted with preformed FS discs containing tetracycline free-base to evaluate control of peritoneal sepsis and to measure serum tetracycline levels. Infection was initiated with Staphylococcus aureus. Morbidity and mortality were evaluated for 14 days. Serum was isolated from jugular vein blood with subsequent evaluation for antimicrobial activity. Mice prophylactically treated with FS-tetracycline (FS-TET) 500 mg/kg 2 days before infection cleared the S. aureus infection, resulting in 100% survival. Mice treated with FS-TET 500 mg/kg 7 days before infection survived. Mice treated with FS-TET 1750 mg/kg 35 days before infection also survived. Rats treated with FS-TET 500 mg/kg had undetectable serum tetracycline levels, whereas in vitro release of tetracycline from FS-TET pellets in rat serum was readily detected. We conclude that fibrin is an excellent vehicle for extended delivery of low solubility tetracycline. Tetracycline delivered from FS is an appropriate chemotherapy for S. aureus peritonitis. FS-TET controls localized infection without a measurable concentration of systemic tetracycline.
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PMID:Tetracycline delivery from fibrin controls peritoneal infection without measurable systemic antibiotic. 1173 70

A variety of interventional techniques have been developed to restore function to dysfunctional tunneled hemodialysis catheters (THC). The relative efficacies of these techniques were evaluated retrospectively to determine which therapy might be most beneficial. The records of malfunctioning THCs referred to interventional radiology between November 1995 and December 1999 were retrospectively reviewed. Dysfunctional THCs were studied using DSA images obtained while injecting contrast through the lumens of the THCs. The interventions performed were categorized into 1 of 5 groups: no treatment or conservative measures such as vigorous flushing; advancing a guidewire through the THC to reposition the catheter tip or to dislodge a small thrombus; catheter exchange over a guidewire; fibrin stripping of the THC using a loop snare; or prolonged (4 or more hr) direct thrombolytic infusion. A Cox Proportional Hazards model was developed to compare the rate of failure among the procedures. There were 340 THC studies. The catheters were managed as follows: 93 patients received conservative management only, 15 had a guidewire advanced through the catheter, 147 underwent catheter exchange, 62 were treated with a fibrin stripping procedure, and 23 received a thrombolytic infusion. Estimated 30-day patency rates for THCs were 38.2% for conservative management, 30.9% for guidewire manipulation of catheter tip, 53.6% for catheter exchange, 76.1% for fibrin stripping, and 69.8% for thrombolytic infusion. Differences among the treatments were observed (p < 0.01) and pairwise comparisons were made among the treatment groups. Failure rates were significantly higher in the catheter exchange (p <0.01) and guidewire manipulation at catheter tip (p <0.01) groups when compared with the fibrin stripping group. The catheter exchange and guidewire manipulation groups also experienced higher rates of failure when compared with the thrombolytic infusion group, although the differences were not statistically significant (p = 0.08, p = 0.17, respectively). Four procedure-related complications requiring hospitalization or other intervention occurred. Three of these were in the catheter exchange group with one incidence of sepsis, one drug reaction, and one hematoma. Fibrin stripping and thrombolytic infusion provided the greatest efficacy in the treatment of poorly functioning THCs, but all therapies demonstrated wide-ranging results. Central line exchanges did not provide a superior secondary patency and experienced more complications.
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PMID:Utility of percutaneous intervention in the management of tunneled hemodialysis catheters. 1239 16

Disseminated intravascular coagulation (DIC) is a systemic thrombohemorrhagic disorder seen in association with many clinical situations, e.g. sepsis, malignancy, obstetrical complications and intravascular hemolysis. In our model, disseminated intravascular coagulation was induced in rabbits by two consecutive intravenous bolus injections of endotoxin from Escherichia coli, 80 and 40 microg/kg. The control group was treated with 0.9% saline. The activity of thioglycosides was compared to unfractionated heparin (UFH) and efegatran with and without administration of endotoxin. Drugs were administered in the following doses: heparin 50 and 100 IU/kg/h i.v. infusion; efegatran 0.25 and 0.5 mg/kg/h i.v. infusion; GYKI 39521 (RGH-1875) as well as GYKI 39541 (RGH-1962) 12.5 and 25 mg/kg per os. Thioglycosides did not modify coagulation parameters in this model [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT)] as compared with endotoxin/vehicle group. The changes in TFPI level after administration of thioglycosides and heparin were similar in the mentioned model to those without endotoxin. Endotoxin-induced changes of leukocyte count were not affected by GYKI 39521 and GYKI 39541 treatment in our model. Diminution of fibrinogen level and platelet count was prevented by GYKI 39521 and GYKI 39541. Fibrin degradation products and fibrinolysis were significantly decreased by GYKI 39521 and GYKI 39541. The thioglycosides may have a lower risk of bleeding in the treatment of disseminated intravascular coagulation than heparin.
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PMID:Effect of some new thioglycosides on endotoxin-induced disseminated intravascular coagulation in rabbits. 1256 24

The adult respiratory distress syndrome (ARDS) is a form of acute lung injury that is characterized by florid extravascular fibrin deposition. Thrombosis in the pulmonary vasculature and disseminated intravascular coagulation have also been observed in association with ARDS. Fibrin deposition does not occur in the normal lung but is virtually universal in acute lung injury induced by disparate insults. A large body of basic and preclinical evidence further implicates abnormalities of pathways of fibrin turnover in the pathogenesis of acute inflammation and fibrotic repair. Coagulation is locally upregulated in the injured lung, while fibrinolytic activity is depressed. These abnormalities occur concurrently and favor alveolar fibrin deposition. The systemic derangements of fibrin turnover in sepsis are similar to those that occur in the injured lung. Recent clinical trials demonstrate that interventions using selective anticoagulation can provide a mortality advantage and that selective anticoagulants differ in their ability to provide clinical benefit. Preclinical trials in primates with sepsis-induced ARDS now indicate that anticoagulant interventions that block the extrinsic coagulation pathway can protect against the development of pulmonary fibrin deposition as well as lung dysfunction and acute inflammation. These observations provide proof of principle that key steps in the coagulation cascade are appropriate therapeutic targets to prevent the development of acute lung injury in ARDS. Ongoing studies and prior publications also support the hypothesis that reversal of the fibrinolytic defect in ARDS could protect against the development of acute lung injury. In all, these studies suggest that fibrin deposition in the injured lung as well as abnormalities of coagulation and fibrinolysis are integral to the pathogenesis of ARDS. The ability of selective anticoagulants to effectively and safely alter clinical outcome in ARDS remains to be determined.
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PMID:Adult respiratory distress syndrome: do selective anticoagulants help? 1472 25

Fibrin persistence in the vasculature is an important complication of sepsis that can often lead to mortality. We have previously established that polymorphonuclear leukocytes (PMN) from healthy individuals have the capacity to degrade fibrin via urokinase-type plasminogen activator (u-PA). We have also demonstrated an increase in u-PA antigen in the plasma of patients suffering from septic shock. In this study, we investigate the hypothesis that PMN from patients with sepsis have lost their fibrinolytic ability and that this might contribute to the persistence of fibrin deposits. We show here that PMN from these patients do not express any u-PA activity, despite retaining some u-PA antigen. Additionally, thrombi prepared from the whole blood of the patients exhibit reduced endogenous lysis compared with those from healthy individuals. These data indicate that loss of fibrinolytic activity from PMN may be a contributing factor in fibrin persistence in the microvasculature in sepsis.
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PMID:Polymorphonuclear leukocytes from patients with severe sepsis have lost the ability to degrade fibrin via u-PA. 1527 68

The problem of obesity has reached epidemic proportions in the USA. More than 50% of adults are obese or overweight. The only therapeutic intervention that provides effective long-term weight loss for the severely obese is bariatric surgery. Roux-en-Y gastric bypass is the most commonly performed bariatric operation in the USA. Anastomotic leaks can cause life-threatening sepsis in the immediate postoperative period or delayed presentations with fistulas. Fibrin sealant and bovine pericardium have been used to reinforce the anastomosis in order to decrease the rate of this dreaded complication. This review will summarize current literature on the subject.
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PMID:Staple-line buttressing material in gastric-bypass surgery. 1629 71

We evaluated the score for disseminated intravascular coagulation (DIC) recently published by the International Society for Thrombosis and Haemostasis (ISTH) in a well-defined series of sepsis patients. Thirty-two patients suffering from severe sepsis and eight patients with septic shock were evaluated following the ISTH DIC score. Fibrin monomer and D-dimer were chosen as fibrin-related markers (FRM), respectively. DIC scores for nonsurvivors (n = 13) as well as for septic shock patients were higher (P < 0.04) compared with survivors and patients with severe sepsis, respectively. Using fibrin monomer and D-dimer, 30 and 25% of patients suffered from overt DIC. Overt DIC was associated with significantly elevated thrombin-antithrombin complexes and plasminogen activator inhibitor type-1 levels as well as with significantly lower factor VII clotting activity. Patients with overt DIC had a significantly higher risk of death and of developing septic shock. Since more than 95% of the sepsis patients had elevated FRM, the DIC score was strongly dependent on prolongation of the prothrombin time and platelet counts. The ISTH DIC score is useful to identify patients with coagulation activation, predicting fatality and disease severity. It mainly depends on the prolongation of the prothrombin time and platelet counts.
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PMID:International Society on Thrombosis and Haemostasis score for overt disseminated intravascular coagulation predicts organ dysfunction and fatality in sepsis patients. 1690 47


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