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)

Actin has been found to bind to plasmin's kringle regions, thereby inhibiting its enzymatic activity in a noncompetitive manner. We, therefore, examined its effect upon the conversion of plasminogen to plasmin by tissue plasminogen activator. Actin stimulated plasmin generation from both Glu- and Lys-plasminogen, lowering the Km for activation of Glu-plasminogen into the low micromolar range. Accelerated plasmin generation did not occur in the presence of epsilon-amino caproic acid or if actin was exposed to acetic anhydride, an agent known to acetylate lysine residues. Actin binds to tissue plasminogen activator (t-Pa) (Kd = 0.55 microM), at least partially via lysine-binding sites. Actin's stimulation of plasmin generation from Glu-plasminogen was inhibited by the addition of aprotinin and was restored by the substitution of plasmin-treated actin, indicating the operation of a plasmin-dependent positive feedback mechanism. Native actin binds to Lys-plasminogen, and promotes its conversion to plasmin even in the presence of aprotinin, indicating that plasmin's cleavage of either actin or plasminogen leads to further plasmin generation. Plasmin-treated actin binds Glu-plasminogen and t-PA simultaneously, thereby raising the local concentration of t-PA and plasminogen. Together, but not separately, actin and t-PA prolong the thrombin time of plasma through the generation of plasmin and fibrinogen degradation products. Actin-stimulated plasmin generation may be responsible for some of the changes found in peripheral blood following tissue injury and sepsis.
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PMID:Actin accelerates plasmin generation by tissue plasminogen activator. 183 75

The authors give an account on the relations between disseminated intravascular coagulation, sepsis and multiorgan failure. Disseminated intravascular coagulation is defined as an acquired disorder of blood clotting with an increased turnover of thrombocytes, fibrinogen and coagulation factors. The authors discuss aetiopathogenetic aspects, possibilities of laboratory diagnosis, anticoagulation and substitution therapy and prophylaxis of disseminated intravascular coagulation in septicaemia. They emphasize comprehensive treatment of septicaemias where haematological monitoring and therapy must form an integral part. In an extensive series of septic multiorgan failures the authors detected failures apparent on laboratory examination in 41% of the patients.
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PMID:[Disseminated intravascular coagulation and sepsis]. 184 51

Meningococcal sepsis with cardiovascular manifestations is one of the leading causes of pediatric intensive care admission (14.85%) in our area. We carried out a two phase study over period of 10 years from 1979 to 1988, involving a retrospective analysis of clinical and analytical manifestations in order to determine a prognostic score of the severity of meningococcal infections in our area. A total of 86 cases were studies over a two year period. After establishing the prognostic score, we applied a previously assayed therapeutic protocol, based on the number of criteria of severity, in 170 children selected as having the same criteria. The factors of seriousness considered were: Appearance of the first symptoms less than 12 h. previously, appearance of petechia less than 6 h. previously, hyperthermia, shock at admission, absence of meningitis, fulminating course of purpura and convulsions, leukopenia less than or equal to 5,000 mm3, prothrombin activity less than or equal to 45%, platelets less than or equal to 75,000 mm3, fibrinogen less than or equal to 250 mgrs% and FPD greater than 40 micrograms/ml (p less than or equal to 0.01 (CHI SQUARE]. In the first phase of study, overall mortality was associated with the presence of three criteria, and was highest when more than seven criteria were present. The results indicate that mortality from meningococcal sepsis is linked to fulminating deterioration of hemodynamics and DIC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Meningococcal sepsis in our area. Study of the disease severity factors and therapeutic management over a 10-year period]. 188 8

Thrombolytic therapy usually used for thrombosis in the adult has been administered as a therapeutic regiment in pediatric patients (parental consent was sought prior to the treatment with rt-PA). We report our experience with rt-PA in 17 children and adolescents suffering from arterial (n = 4) or venous thrombosis (n = 13) due to local rhabdomyosarcoma, acute lymphoblastic leukemia, chronic myeloblastosis, sickle cell anaemia, parenteral nutrition, haemolytic uremic syndrome, central arterial and venous catheters and septicemia Thrombotic diseases have been diagnosed by Doppler ultrasound, computed tomography, angiography and phlebography. Rt-PA therapy was started immediately after diagnostic procedures had been performed. Rt-PA dose varied from 0.2 mg as a single dose to 0.8 mg/kg bw/d over a three day period in children local thrombolysis was performed. In patients requiring systemic thrombolytic therapy rt-PA was administered from 0.8 mg/kg bw/d in three days to 2.0 mg/kg bw/d over a whole period of three weeks in both groups during thrombolysis low dose heparin was added. When rt-PA infusion was terminated heparin (70 IU - 400 IU/kg bw/d) was administered for 7 to 14 days in order to prevent reocclusion. Later prophylaxis with coumarin derivatives in venous thrombosis and antiplatelet agents in arterial occlusive diseases was performed. In no patient did we see a decrease of fibrinogen and plasminogen during rt-PA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Thrombolysis with rt-PA in children with arterial and venous thromboses--a new therapy concept]. 194 42

The study objective was to describe the clinical, biologic, and hemodynamic features of adult overwhelming meningococcal purpura and to examine the prognostic factors by multivariate analysis at the time of admission to the intensive care unit. Thirty-five patients (greater than or equal to 13 years of age) with meningococcal infection, circulatory shock, and generalized purpuric lesions of abrupt onset were recorded in eight intensive care units from 1977 to 1989. The patients were young (mean age, 26.6 years; range, 13 to 68 years) and had been previously healthy. The female-to-male ratio was 3:1. Mortality was 54.3%, with most deaths occurring within the first 48 hours, usually secondary to irreversible shock with multiple organ failure. Ischemic complications (eight cases), prolonged heart failure (seven cases), and secondary septicemia (five cases) were the chief complications among survivors. Initial hemodynamic study after volume loading showed low stroke volume index (mean +/- SD, 29.4 +/- 13 mL/m2) and tachycardia (mean +/- SD, 138 +/- 16 beats per minute), a profile suggesting a greater myocardial depression than usually observed in gram-negative bacillary septic shock. Univariate prognostic analysis showed that four variables at the time of admission were associated with fatal outcome: a plasma fibrinogen level of 1.5 g/L or less, a factor V concentration of 0.20 or less, a platelet count lower than 80 x 10(9)/L, and a cerebrospinal fluid leukocyte count of 20 x 10(6)/L or less. Stepwise regression analysis showed that low fibrinogen level (less than or equal to 1.5 g/L) was the sole adverse prognostic variable (odds ratio = 2, 95% confidence interval, 1.5 to 2.7). Adult overwhelming meningococcal purpura is still associated with high mortality and morbidity. Low fibrinogen level at time of admission may permit early recognition of the most severely ill patients.
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PMID:Adult overwhelming meningococcal purpura. A study of 35 cases, 1977-1989. 199 58

One of the aims of research in the area of thrombosis has been to design an effective anticoagulant that would function in a predictable and direct manner. In evaluating the role of coagulation in sepsis we used factor Xa blocked in the active center with [5-(dimethylamino)1-naphthalenesulfonyl]-glutamylglycylarginyl+ ++ chloromethyl ketone (DEGR-Xa). We infused 1 mg/kg of DEGR-Xa together with LD100 concentrations of Escherichia coli (4 x 10(10) organisms/kg) into five baboons. As controls, we infused E coli alone into five baboons. The inflammatory, coagulant, and cell injury responses to E coli of both the treated and control groups were lethal and were similar in every respect except for the complete inhibition of the consumption of fibrinogen in the DEGR-Xa group. The half life of DEGR-Xa was approximately 10 hours and 2 hours, as determined by isotopic and enzyme-linked immunosorbent assays, respectively. These results for the first time demonstrate that, although coagulation occurs in E coli sepsis, fibrin formation per se did not influence the lethal outcome in this model. These results also show the effectiveness of DEGR-Xa as an anticoagulant and raise the possibility that it could serve as an alternative to anticoagulants currently in use.
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PMID:DEGR-factor Xa blocks disseminated intravascular coagulation initiated by Escherichia coli without preventing shock or organ damage. 207 73

The levels of fibronectin, alpha-1 antitrypsin, and fibrinogen have been studied in 34 patients after orthotopic liver transplantation (OLT). Patients were grouped according to A: postoperative course without complications (n = 18), B: development of sepsis accompanied by organ insufficiency (n = 8), and C: acute rejection (n = 6). The plasma levels of alpha-1 antitrypsin and fibrinogen did not show a typical pattern with respect to the postoperative course. The levels of fibronectin, however, did respond to the postoperative events. Starting from a subnormal level a significant increase was observed in group A (p less than 0.005) and C (p less than 0.05) whereas in group B plasma levels remained low. Significant differences (p less than 0.05) were found on day 3 and 5 between group A and C and group B and C. At the end of the observation period survivors (group A and C) had significantly higher levels of fibronectin than nonsurvivors (group B). Therefore fibronectin might aid to diagnose immunologic disturbances after OLT.
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PMID:[Plasma proteins in the early postoperative course after liver transplantation]. 209 69

The neonatal period is probably the only time when a higher incidence of spontaneous thromboembolic complications may occur in the otherwise normal healthy individual, and this may be related to the activation of the coagulation system at the time of parturition. This study was performed to look at the newborn coagulation and anticoagulation systems and compare these with the changes in the maternal circulation in normal cases. Paired umbilical cord venous and maternal venous blood samples were obtained and plasma levels of protein C, protein S, antithrombin III, fibrinopeptide A, fibrinogen, plasminogen, and fibrinolytic inhibitory activity were measured. The maternal plasma level was significantly higher in all cases except for fibrinopeptide A which was similar, and for fibrinolytic inhibitory activity which was lower (p less than 0.05). A significant correlation exists between maternal and newborn protein C levels (p less than 0.02) and fibrinolytic inhibitory activity (p less than 0.05). The findings indicate that parturition leads to a similar degree of activation of the newborn coagulation system as shown by the fibrinopeptide A level. As their anticoagulants and fibrinolytic activity levels are lower and the fibrinolytic inhibitory activity is higher, the newborns are thus predisposed to thrombosis even in the absence of complications such as sepsis.
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PMID:Coagulation and anticoagulation systems in newborns--correlation with their mothers at delivery. Lower levels of anticoagulants and fibrinolytic activity in the newborn. 214 83

Cecal ligation and puncture (CLP) were performed in rats. After 4 hr (early sepsis) and 16 hr (late sepsis), platelet morphology and function were studied. At 16 hr, platelet counts for the CLP group were significantly lower than for the sham-operated control group. Low maximum aggregation rates (MAR) and decreased platelet counts were elicited in platelet-rich plasma with 4 M ADP and 2 micrograms/ml collagen. However, with platelet counts equalized, MAR for the CLP group increased significantly, especially after 16 hr. The platelet-large cell rate and platelet distribution width decreased temporarily at 4 hr, then rose significantly at 16 hr. No significant changes were observed in the mean platelet volume after 4 hr, but there were significant increases after 16 hr. Total adenine nucleotide (TAN) levels within the platelets rose significantly in the CLP group, suggesting the appearance during the late sepsis of large, heavy platelets or adenine nucleotide-rich platelets. The platelet adenylate pool was divided into granular and cytoplasmic fractions, respectively characterized by ADP and ATP increases. However, no septicemia-related differences were noted in the degree of binding between goat antirat fibrinogen and platelet surface glycoprotein IIb/IIIa complex. Internal environment changes in the platelets indicated that during septicemia hyperfunctional or hypersensitive platelets with a latent capacity for active aggregation and release appeared in the circulation. Hypercoagulability in septicemia involves activation of coagulation factors, stimulation of the coagulation cascade, volume changes accompanying increased platelet TAN content, and changes in AN distribution in the two pools. These findings significantly increase our understanding of the transition from the prethrombotic state to thrombosis in septicemia.
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PMID:Platelet size and function in septic rats: changes in the adenylate pool. 217 92

To elucidate the role of leukocytes in intravascular clotting in patients with septicemia, plasma levels of thrombin-antithrombin III complex (TAT), soluble fibrin monomer complex (SFMC) and fibrinogen (Fbg) were determined in 33 patients with septicemia. Twenty out of 33 patients revealed a marked leukopenia (leukocyte count was less than 1,000/microliters) due to suppression of hematopoiesis by the administration of chemotherapeutic agents for the treatment of hematological malignancies. Thirteen out of 33 patients showed normal or increased leukocyte counts. Plasma levels of TAT and SFMC in septicemic patients with leukopenia were significantly lower than those in patients whose leukocyte counts were higher than 1,000/microliters. Plasma fibrinogen levels were significantly lower in patients whose leukocyte counts were higher than 1,000/microliters than those in patients with leukopenia. Plasma TAT levels were found to correlate well with the number of leukocytes in these patients with the correlation coefficient (R) of 0.67 (p less than 0.001). Significantly high positive correlation was observed between plasma TAT levels and the number of monocytes (R = 0.92, p less than 0.001). Significant correlation was also observed between plasma SFMC levels and the number of monocytes (R = 0.72, p less than 0.001). No significant correlation was found between the number of platelets and TAT levels. These findings suggest that leukocytes (especially monocytes) play a critical role in activating intravascular coagulation in septicemic patients.
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PMID:[Studies on the role of leukocytes in the activation of intravascular coagulation in septicemia]. 220 43


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