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)

We describe a newborn infant with veno-occlusive disease (VOD) of the liver. Prior to discharge from the hospital, the newborn, who had been treated for suspected neonatal infection, suddenly developed sepsis-like symptoms. The size of the liver as well as serum activity of hepatic enzymes increased progressively. Initial Doppler-flow studies demonstrated an absent flow in the vena portae, a finding that was compatible with vena portae thrombosis or occlusion of other hepatic veins. A therapy with recombinant tissue plasminogen activator (rt-PA) was initiated; due to extensive bleedings from various sides, the fibrinolytic therapy had to be withdrawn 12 hours later, when Doppler-flow examination revealed a reverse flow in hepatofugal direction. Despite supportive therapy, the general condition of the patient deteriorated continuously, finally resulting in liver and renal failure. Our patient died 19 days after birth. The autopsy demonstrated obliterative lesions of the centrilobular and sublobular hepatic veins, the classical signs of VOD of the liver. Despite extensive diagnostics and examinations, the etiology of VOD could not been elucidated in this newborn.
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PMID:Fatal hepatic veno-occlusive disease in a newborn infant. 925 9

This article reports about a young boy with fulminant meningococcal septicemia. Conventional treatment with antibiotics, intensive care and hemostatic drugs hold up vital functions. Because of extensive purpura fulminans with skin necrosis recombinant tissue plasminogen activator (rt-PA) was used. Under this therapy clinical improvement was observed.
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PMID:[Recombinant tissue plasminogen activator in treatment of fulminant meningococcal infection]. 944 24

Patients in intensive care may be at high risk of in vivo platelet activation because comorbid conditions, such as infections, septicemia, shock, disseminated intravascular coagulation, and cancer represent procoagulant states. Hyperreactivity of platelets with or without a decline of cell count may result in thromboembolic complications potentially associated with the phenomenon of heparin-induced thrombocytopenia. We analyzed the data of 10 patients highly suspected of having heparin-induced thrombocytopenia during their intensive care treatment of 29 plus or minus 22 days. In seven patients, thrombocytopenia coincided with thromboembolic complications. Six patients had additionally undergone fibrinolytic therapy before starting activated partial thromboplastin time-adapted alternative anticoagulation with r-hirudin. In three patients, the platelet count decreased without a clinical manifestation, of heparin-induced thrombocytopenia. R-Hirudin treatment monitored by activated partial thromboplastin time and prothrombin time (PT) was effective and safe. The target value for activated partial thromboplastin time was a twofold prolongation. In four of five patients with deep venous thrombosis, a partial recanalization of the lower extremity could be achieved. Three patients with pulmonary embolism associated with deep venous thrombosis in two cases and in one additional case with an acute myocardial infarction did clinically profit from fibrinolysis with recombinant tissue plasminogen activator (rtPA) and r-hirudin treatment. Two lethal events probably caused by the underlying multimorbidity could not be prevented. No recurrence of thrombosis occurred, and there were no severe bleeding complications attributed to r-hirudin treatment. Platelet counts were significantly reduced on day 9.4 plus or minus 6.4 of heparin administration in all cases (>50% decrease related to the initial values) from 224,000 plus or minus 126,000/microL to 96,000 plus or minus 61,000/microL, and increased during rhirudin treatment to mean values of 224,000 plus or minus 126,000/microL. The heparin-induced platelet activation assay (HIPAA) assay was positive in 8/10 cases, whereas the PF4 enzyme-linked immunosorbent assay showed a positive result in four of eight analyzed cases. In four cases, the assays were concordantly positive. The PF4 enzyme-linked immunosorbent assay was not performed in two cases.
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PMID:Heparin-induced thrombocytopenia: a critical risk/benefit analysis of patients in intensive care treated with R-hirudin. 1089 75

In a porcine model of Gram-positive sepsis, 28 juvenile pigs were studied to evaluate the effect of a continuous infusion of live serogroup A streptococci (GAS) on the activation of coagulation and fibrinolysis. Plasma levels of thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities were measured using commercially available kits. The continuous infusion of GAS [(3-5) x 10(8) colony-forming units/kg per h] caused early signs of severe septicaemia in the pigs, with pulmonary hypertension, systemic hypotension, reduced cardiac output and liver hypoperfusion, ultimately leading to shock with a high mortality. There was a sequential and ordered activation of the coagulation, fibrinolytic and antifibrinolytic systems. GAS infusion induced a gradual, maximally 2.5-fold increase in plasma TAT levels. Plasma t-PA activity levels peaked at 2 h (nine-fold increase), whereas the peak of PAI-1 activity was delayed (eight-fold increase at 4 h). These findings are similar to changes observed during endotoxin infusion. This procoagulant state favours disseminated intravascular coagulation and microthrombus formation, ultimately threatening tissue viability.
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PMID:Systemic activation of coagulation and fibrynolysis in a porcine model of serogroup A streptococcal shock. 1093 4

Endothelial damage plays a central role in the development of an SIRS-related Multiple Organ Dysfunction Syndrome (MODS) as a consequence of the establishment of a hemostatic imbalance between coagulation and fibrinolysis systems. Until now, sepsis is the SIRS model that has been most studied. The aim of this study was to assess the endothelial damage and the hemostatic imbalance in early stages of an SIRS of different origins, and to study if there are any differences in these disturbances between infectious and noninfectious SIRS. The endothelial damage and hemostatic changes were studied in 40 patients with SIRS (with less than 12 h of evolution) and an acute renal failure. Infectious SIRS was diagnosed in 19 cases and noninfectious SIRS in the remaining 21 patients. Patients with SIRS presented significantly higher values (p<0.001) for factors related to endothelial damage [von Willebrand factor (vWF), thrombomodulin, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) antigen], hypercoagulability [prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT)], and fibrinolysis (D-dimer and PAI activity) with respect to the control group. However, although the group with infectious SIRS presented higher values for all the factors except for the t-PA and D-dimer with respect to SIRS of other origins, none of these differences reached statistical significance (p>0.05). Our data show that patients with SIRS and associated acute renal failure, irrespective of the origin (infectious or noninfectious), show signs of intense endothelial damage and hypercoagulability throughout the process.
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PMID:Hemostatic disturbances in patients with systemic inflammatory response syndrome (SIRS) and associated acute renal failure (ARF). 1105 12

Increased survival of extremely low birth weight infants depends on the use of indwelling catheters. These catheters expose the infant to the risk of thrombus formation and line infection. When intracardiac thromboses become infected, the entity is indistinguishable from infective endocarditis and exposes the infant to prolonged sepsis and risk of disseminated infected emboli. Despite prolonged antiinfective therapy and removal of the infected line, resolution of the sepsis and dissolution of the vegetations is frequently not achieved. We describe 2 cases of infective endocarditis in extremely low birth weight infants successfully treated with recombinant tissue plasminogen activator in addition to prolonged antiinfective therapy. Blood cultures became sterile and vegetations disappeared within days of commencing treatment, and there were no systemic complications. A literature search detailed in the article confirms the poor outcome associated with infectious endocarditis in preterm infants. Tissue plasminogen activator may play an important role when standard care has failed.
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PMID:Infective endocarditis successfully treated in extremely low birth weight infants with recombinant tissue plasminogen activator. 1177 59

Sepsis and trauma are the two most common causes of disseminated intravascular coagulation and multiple organ dysfunction syndrome. Both disseminated intravascular coagulation and the systemic inflammatory response syndrome often lead to multiple organ dysfunction syndrome. The current studies have evaluated the relationship between the anaphylatoxin, C5a, and changes in the coagulation/fibrinolytic systems during the cecal ligation and puncture (CLP) model of sepsis in rats. CLP animals treated with anti-C5a had a much improved number of survivors (63%) compared to rats treated with pre-immune IgG (31%). In CLP rats treated with pre-immune IgG there was clearly increased procoagulant activity with prolongation of the activated partial thromboplastin time and prothrombin time, reduced platelet counts, and increased levels of plasma fibrinogen. Evidence for thrombin formation was indicated by early consumption of factor VII:C, subsequent consumption of factors XI:C and IX:C and anti-thrombin and increased levels of the thrombin-anti-thrombin complex and D-dimer. Limited activation of fibrinolysis was indicated by reduced plasma levels of plasminogen and increased levels of tissue plasminogen activator and plasminogen activator inhibitor. Most of these parameters were reversed in CLP rats that had been treated with anti-C5a. Production of C5a during sepsis may directly or indirectly cause hemostatic defects that can be reduced by blockade of C5a.
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PMID:Anti-c5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis. 1200 Jul 38

Systemic inflammation because of sepsis results in endothelial cell activation and microvascular injury. High-mobility group protein-1 (HMGB1), a novel inflammatory molecule, is a late mediator of endotoxin shock and is present in the blood of septic patients. The receptor for advanced glycation end products (RAGE) is expressed on endothelium and is a receptor for HMGB1. Here we examine the effects of HMGB1 on human endothelial cell function. Recombinant human HMGB1 (rhHMGB1) was cloned and expressed in Escherichia coli and incubated with human microvascular endothelium. rhHMGB1 caused a dose- and time-dependent increase in the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and RAGE. rhHMGB1 induced the secretion of tumor necrosis factor-alpha (TNFalpha), interleukin 8 (IL-8), monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), and tissue plasminogen activator (tPA) (P <.01). rhHMGB1 stimulation resulted in transient phosphorylation of mitogen-activated protein (MAP) kinases, extracellular signal-related kinase (ERK), Jun N-terminal kinase (JNK), and p38, and in nuclear translocation of transcription factors NF-kappaB and Sp1. These effects are partially mediated by TNFalpha autocrine stimulation, as anti-TNFalpha antibodies significantly decrease chemokine and adhesion molecule responses (P </=.002). Thus, rhHMGB1 elicits proinflammatory responses on endothelial cells and may contribute to alterations in endothelial cell function in human inflammation.
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PMID:Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. 1245 6

Kinins are peptide hormones that exert pathophysiological as well as pronounced beneficial physiological effects, mainly by stimulation of bradykinin (BK) B(2) receptors. Owing to the strong proinflammatory properties of kinins resulting from vasodilation, plasma extravasation, activation of mast cells, fibroblasts and macrophages, stimulation of sensory neurons, and the release of nitric oxide, prostaglandins, leukotrienes and cytokines, kinins are believed to play an important role in a variety of inflammatory diseases and pain. Beneficial effects of BK B(2) receptor antagonists in perennial rhinitis, asthma and brain edema have already been shown in clinical trials. Recently, the potential therapeutic utility of BK B(2) receptor antagonists has been extended by the discovery of orally active, nonpeptide BK B(2) receptor antagonists and the identification of novel indications for their use. On the other hand, kinins also have been identified as potent antihypertensive and organ-protective peptides. They have been shown to have vasodilatory, antihypertrophic, antiaggregatory and fibrinolytic effects due to the BK B(2) receptor-mediated release of the autacoids nitric oxide, prostacyclin and tissue plasminogen activator. A recent finding is that kinins are also involved in ischemic preconditioning. Orally active, nonpeptide BK B(2) receptor agonists as potential novel therapeutic agents in cardiovascular medicine have also been identified. In conclusion, interaction with the BK B(2) receptor by either its blockade or its stimulation offers promising therapeutic approaches. BK B(2) receptor antagonists may prove to be useful in the treatment of asthma, rhinitis, arthritis, colitis, pancreatitis, sepsis, edema, tissue injury, pain and possibly infections, hepatorenal syndrome, Alzheimer's disease and lung cancer. BK B(2) receptor agonists have potential in the treatment of cardiovascular diseases like hypertension, cardiac hypertrophy, restenosis and myocardial infarction and diabetic disorders.
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PMID:Bradykinin B2 receptor as a potential therapeutic target. 1293 26

Superior vena cava syndrome is rare in infants, and rarely responds to conservative treatment. We report a 22-mo-old girl with superior vena cava syndrome due to the use of a central venous line and/or sepsis. Doppler study and computed tomography angiography of the neck showed thrombosis within the superior vena cava and jugular veins. She was admitted to a monitored setting and received recombinant tissue plasminogen activator for 2 d. The clinical features of superior vena cava syndrome disappeared completely 3 d after treatment. No complications were observed and radiological investigations showed blood flow through the thrombus after treatment. Systemic recombinant tissue plasminogen activator may be useful in the treatment of superior vena cava syndrome in children.
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PMID:Thrombolytic therapy with tissue plasminogen activator for superior vena cava thrombosis in an infant with sepsis. 1598 62


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