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)

We measured plasma heparin cofactor II (HC II) activity in patients with disseminated intravascular coagulation (DIC) due to various underlying diseases together with the levels of antithrombin III (AT III), pseudocholinesterase (a marker of hepatic synthesis), and various haemostatic molecular markers. Both HC II and AT III were decreased in DIC secondary to all the underlying diseases studied, except acute promyelocytic leukemia (APL), when compared with healthy subjects. The lowest HC II and AT III levels was observed in coagulopathy secondary to liver disease, the HC II level in sepsis was the second lowest. In DIC due to APL, the decrease in HC II was not accompanied by a decrease in AT III. Thus, we divided all 124 samples tested into APL and non-APL groups. The HC II level correlated positively with fibrinogen and plasminogen in both the APL and non-APL groups. In the APL group, the HC II level had a significant negative correlation with the thrombin-AT III complex (TAT), fibrinogen/fibrin degradation products, and D-dimer levels as well as the prothrombin time, while AT III showed no correlations with any of the haemostatic parameters. These results suggest that HC II may be consumed preferentially by thrombin in APL patients with DIC, and thus may spare the consumption of AT III. Accordingly, HC II seems to be a superior indicator of DIC than AT III in APL patients. Moreover, replacement therapy with HC II instead of AT III may be useful to treat DIC associated with APL. In the non-APL group, the HC II levels were positively correlated with the levels of AT III and pseudocholinesterase activity. This indicates that plasma HC II levels are closely related not only to consumption coagulopathy but also to hepatic synthetic activity, as is the case for plasma AT III.
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PMID:Preferential consumption of heparin cofactor II in disseminated intravascular coagulation associated with acute promyelocytic leukemia. 141 8

We examined the changes in plasma levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, in 47 cases of disseminated intravascular coagulation (DIC) to investigate the role of ET-1 in DIC and its relation to multiple organ failure (MOF). A significant elevation of plasma levels of ET-1 was observed in some cases of DIC, especially in patients with sepsis, blastic crisis of chronic myelogenous leukemia, and cancer. However, no such significant elevation was observed in patients with acute promyelocytic leukemia (APL), acute leukemias except for APL, or non-Hodgkin lymphoma. Plasma levels of ET-1 were higher in patients with DIC with MOF than in those without MOF. Although the levels of ET-1 were decreased or remained low with clinical improvement in most DIC patients, the levels were further increased or remained high in patients who showed no improvement in DIC. It is suggested that ET-1 must play an important role in further progression of MOF with the vasoconstriction and microcirculatory disorders.
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PMID:Role of endothelin in disseminated intravascular coagulation. 141 85

We investigated the imbalance between thrombin and plasmin activity in vivo with various grades of severity of disseminated intravascular coagulation (DIC) in relation to the underlying diseases. Plasma thrombin-antithrombin-III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) levels were measured in 133 blood samples obtained from patients with DIC. The TAT/PAP ratio was higher in patients with sepsis or solid cancer than in those with hematologic malignancies. In acute promyelocytic leukemia (APL), the TAT levels were the highest, but the PAP levels were even higher and the TAT/PAP ratio was the lowest. As for the severity of DIC, in mild DIC, both thrombin and plasmin activities were increased. In moderate DIC, the TAT/PAP ratio increased, and thrombin activity was much more predominant. However, in severe DIC, the ratio decreased, and plasmin activity became excessive. In 3 patients with acute myeloblastic leukemia, APL and pancreatic cancer, respectively, the PAP level remained high during heparin therapy although the TAT level was decreased. When tranexamic acid was given, the PAP level was selectively reduced, and the TAT/PAP ratio was markedly decreased along with clinical improvement. These results indicate that monitoring of the TAT/PAP ratio may contribute to decisions regarding the institution and performance of combination therapy for DIC using anticoagulants and antifibrinolytic agents.
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PMID:Imbalance between thrombin and plasmin activity in disseminated intravascular coagulation. Assessment by the thrombin-antithrombin-III complex/plasmin-alpha-2-antiplasmin complex ratio. 146 20

We examined the changes in plasma levels of soluble thrombomodulin in 66 cases of disseminated intravascular coagulation (DIC), to investigate the damage to vascular endothelial cells and its relationship to multiple organ failure. A significant elevation of plasma levels of soluble thrombomodulin was observed in most cases of DIC, especially in patients with sepsis. However, no such significant elevation was observed in patients with acute promyelocytic leukemia. Plasma levels of both soluble thrombomodulin and active plasminogen activator inhibitor were higher in the cases of DIC with multiple organ failure than in those without multiple organ failure. The levels of soluble thrombomodulin were decreased with the clinical improvement in most cases of DIC but were further increased or remained at high levels in patients who showed no improvement of DIC. It was suggested that an increase in soluble thrombomodulin indicates the damage to the vascular endothelial cells in cases of DIC and that the damage to vascular endothelial cells plays some role in further progression of multiple organ failure.
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PMID:Plasma levels of soluble thrombomodulin increase in cases of disseminated intravascular coagulation with organ failure. 166 Jun 74

In order to assess the thrombin and plasmin generation in vivo in disseminated intravascular coagulation (DIC), plasma levels of thrombin-antithrombin III (ATIII) complex (TAT) and plasmin-alpha 2-antiplasmin (a2AP) complex (PAP) were measured together with standard coagulation and fibrinolytic parameters in 80 patients with DIC. Both TAT and PAP were markedly elevated in patients with DIC. When plotted by the underlying disease categories, differences in the magnitude of the elevations of these complexes were recognized among groups. Patients with acute promyelocytic leukemia (APL) had the highest PAP, the lowest TAT/PAP ratio, low a2AP, and low fibrinogen, indicating that the most excessive fibrinolysis can occur in APL. Similar profiles, although less marked, were observed in patients with other leukemias and vascular diseases. Patients with sepsis showed the highest TAT/PAP ratio and the lowest PAP with no decrease in a2AP or fibrinogen, demonstrating a relatively impaired fibrinolysis. Patients with cancer had a relatively high TAT and high TAT/PAP ratio. In addition, both TAT and PAP were markedly elevated in patients with shock. From these, it was suggested that, although laboratory manifestations in DIC are extremely variable from patient to patient, underlying disorders are, at least in part, responsible for the observed variations. Recognition of this variable activation of coagulation and fibrinolysis would be helpful for the proper management of patients with DIC.
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PMID:Thrombin vs. plasmin generation in disseminated intravascular coagulation associated with various underlying disorders. 200 32

Plasma levels of tissue-plasminogen activator.plasminogen activator inhibitor (t-PA.PAI) complex and active PAI were assayed in 58 cases of disseminated intravascular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, especially in patients with non-Hodgkin lymphoma, sepsis, or some patients with acute leukemia, but no such elevation was observed in patients with acute promyelocytic leukemia (APL). The levels of both parameters were higher in cases of DIC with multiple organ failure (MOF) than in those without MOF. Since no elevation of t-PA.PAI complex was observed in most cases of APL, t-PA did not seem to play an important role in the activation of fibrinolytic system in APL. Active PAI, which reflects the inhibitory regulation in fibrinolytic system, was considered to play a role in the progression of MOF. Plasma levels of active PAI were low in the cases of APL, which had no complication of MOF.
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PMID:Changes in plasma levels of tissue-plasminogen activator/inhibitor complex and active plasminogen activator inhibitor in patients with disseminated intravascular coagulation. 130 60

Two hundred and sixty-two patients (actual number 162) of hematological malignancies were admitted to our department from November 1977 to December 1986. Fourty-three of them (16.4%) were demonstrated to be accompanied with sepsis by blood culture. In acute non-lymphocytic leukemias (AML, APL, AMoL) the rate of sepsis was 33.8% (27 patients), while in lymphocytic malignancies (ML, HD, ATL) it was 11.7% (16 patients), particularly being 3.0% in ATL. Among the detected pathogenic microorganisms, gram-negative bacilli were 86.2% in the former and 50.0% in the latter. Especially, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli occupied 58.6% of the total in the former. Laboratory examination, when sepsis occurred, revealed peripheral neutropenia in acute non-lymphocytic leukemias (mean 831/cmm) but not in lymphocytic malignancy (mean 4,420/cmm). And 20 of the 27 cases showed remarkable neutropenia of below 500/cmm in the former. On the other hand in the latter, out of 16 only one with ATL was the case. Hypogammaglobulinemia was one of the characteristic features in lymphocytic malignancies but not in acute non-lymphocytic leukemias. Hypogammaglobulinemia in lymphocytic malignancies might be affected by long-term immunodepressant therapy. Immunologic skin reaction was demonstrated to be decreased in lymphocytic malignancies on admission. From the findings mentioned above, affecting factors to infections may be mainly neutropenia in acute non-lymphocytic leukemias and immunodeficiency in lymphocytic malignancies. And sepsis can occur frequently under neutropenic condition. In ATL both of humoral- and cellular-immunologic disturbance were detected before therapy. But peripheral neutrophil count was maintained to be normal and this could be the reason for the low septic incidence in ATL despite of total immunodepression.
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PMID:[Infections in hematological malignancies--clinical analysis of septic patients admitted to the Second Department of Miyazaki Medical College Hospital in the past ten years]. 240 13

In order to assess precisely the fibrinolytic state in disseminated intravascular coagulation (DIC), plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP) and fibrinogenolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme-linked immunosorbent assays based on monoclonal antibodies in 72 patients with DIC at presentation. Not only FbDP and TDP but also FgDP were markedly elevated in patients with DIC. When analyzed according to the underlying disease categories, the relative proportion of FgDP to TDP was high in patients with acute promyelocytic leukemia and vascular diseases, and it was the lowest in patients with sepsis. Correlation analysis revealed that plasma levels of FgDP correlated negatively with alpha 2-antiplasmin and positively with plasmin-alpha 2-antiplasmin complex (PAP) and a ratio of PAP to thrombin-antithrombin III complex (TAT). These findings indicate that besides fibrinolysis, fibrinogenolysis is markedly accelerated in the majority of the patients with DIC.
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PMID:Fibrinolysis and fibrinogenolysis in disseminated intravascular coagulation. 240 38

In the present study plasma fibronectin levels were determined in patients with hematopoietic malignancy, particularly leukemias, in an effort to clarify their clinical implications. Among leukemia patients, those with AML, ALL, ATL or CLL had various plasma fibronectin levels that were higher in some cases, while lower in others, as compared to normal control values. An elevation of the fibronectin level was noted often in APL, while lower fibronectin values were observed in many instances of CML. In these types of leukemia, acute exacerbation as well as supervention of infection tended to be associated with lower than normal levels of fibronectin. An especially marked depression of fibronectin occurred, when leukemia was complicated by sepsis or DIC, in which a good parallel was noted between the progress of disease and the fibronectin level. In lymphoproliferative diseases, the fibronectin value varied widely, but low fibronectin levels were frequently associated with intercurrent infection or an extreme deterioration of the general physical conditions.
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PMID:Variation of plasma fibronectin levels in leukemia patients. 248 45

Pharmacokinetics of ceftizoxime (CZX), a new cephalosporin antibiotic, was investigated in 9 children with normal renal and hepatic function. In addition, the clinical effect of CZX was evaluated in 26 pediatric patients with various infections. In 4 of the 9 children with normal renal and hepatic function, intravenous bolus injection of CZX in a dose of 20 mg/kg yielded a mean peak serum level of 36.5 micrograms/ml at 1/2 hour after infusion, and mean serum levels of 12.5 micrograms/ml at 2 hours and 6.0 micrograms/ml at 4 hours after infusion. The biological half-lives of CZX were estimated to be 1.25--2.55 hours. In another child, serum levels of CZX at 1/2, 2 and 4 hours after intravenous bolus injection in a dose of 10 mg/kg were 19.60, 5.96 and 2.06 micrograms/ml, respectively. The clear difference in dose response between 20 mg/kg and 10 mg/kg reflected the doubled dose levels. In the remaining 4 children, drip infusion of CZX in a dose of 20 mg/kg (1 child 17 mg/kg) over 0.5--1.5 hours yielded peak serum levels at the end of infusion. The biological half-lives of CZX were estimated to be 0.95--1.50 hours. About 80% of CZX was excreted in the urine within 6 hours after infusion in the 4 children tested. Twenty-six pediatric patients with various infections were treated with CZX intravenous doses of 20 mg/kg to 118 mg/kg b.i.d.--q.i.d. for 3--14 days. Of the 12 patients with acute bronchitis and pneumonia, 5 showed excellent response, 6 good and 1 fair response. Of the 5 patients with urinary tract infection, 4 showed excellent response and 1 good response. One patient each with colitis, tonsillitis and facial cellulitis, pharyngitis showed excellent response and 1 patient each with purulent thyroiditis and gluteal abscess showed good response. The single patients with sepsis showed excellent response. One patient each with pyothorax, purulent arthritis and cerebral abscess showed poor response. Overall effectiveness rate was 84.6%. although 22 of all 26 patients treated had serious underlying diseases such as APL, AML. A mild increase in GOT and GPT was observed in 1 patient during treatment with CZX, and the values returned to normal after discontinuation of the drug. These results suggest that ceftizoxime is 1 of the most important antibiotics for treating a wide range of infections in children as well as in adults.
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PMID:[Pharmacokinetics and clinical evaluation of ceftizoxime (author's transl)]. 627 8


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