Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case of an 8-month-old male with heterozygous coagulation protein C deficiency is presented. Sepsis due to Salmonella typhi aggravated the protein C deficiency and resulted in arterial thrombosis of the distal third of the lower right limb. The patient was treated with both heparin and danazol, the levels of functional protein C increasing and the necrotic phenomenon resolving, thus making unnecessary amputation of the limb. The observation is discussed with the evidences of danazol being useful in the treatment of patients with protein C deficiency.
 ...
PMID:[Effect of danazol on heterozygous c protein coagulation deficiency exacerbated by Salmonella typhi sepsis]. 275 77

The levels of protein C (PC) and other coagulation factors were monitored during endotoxin-induced disseminated intravascular coagulation (DIC) in the dog. Initial evaluation of the effectiveness of intradermal administration of bolus endotoxin quantities into the dog, demonstrated induction of DIC in the canine, without the severe side effects associated with bacterial sepsis. Quantitative determination of canine plasma protein C levels were performed using a multiple step amidolytic assay, that included a specific precipitation of the vitamin K-dependent proteins from citrated plasma, followed by thrombin activation (and neutralization) and subsequent measurement of the activated protein C (APC) by chromogen hydrolysis. This investigation demonstrated, that over a twenty-four hour interval, intradermal administration of endotoxin produces a gradual decrease in the PC activity levels, concomitant with a significant reduction in the Factor V, Factor VIII and fibrinogen levels and platelet count, and a prolongation of the Prothrombin Time and Partial Thromboplastin Time. During the first 6 hours, protein C levels fell below the pre-levels and remained significantly lower in the surviving dogs. Thus, this endotoxin-induced DIC animal model permits evaluation of various hemostatic parameters, yet diminishes the severe clinical findings associated with DIC.
 ...
PMID:Protein C activity levels in endotoxin-induced disseminated intravascular coagulation in a dog model. 278 30

Tumor necrosis factor/cachectin (TNF) is a mediator of the septic shock state, which can modulate hemostatic properties of the vessel wall. The interaction of TNF with endothelium is not cytotoxic, rather it is receptor mediated and results in a change in receptor expression on the endothelial cell surface, enabling endothelium to actively promote coagulation. Anticoagulant mechanisms, including the protein C/protein S system and fibrinolysis are suppressed, whereas the initiation and propagation of procoagulant activity is enhanced. This unidirectional shift in vessel wall coagulant activity favoring clot formation could contribute to the coagulopathy associated with sepsis and indicates a mechanism through which the coagulation system serves as an integral part of the host response.
 ...
PMID:Tumor necrosis factor/cachectin-induced modulation of endothelial cell hemostatic properties. 282

To obtain quantitative information on the in vivo activation of the protein C system during the acute phase of sepsis, several components of the protein C pathway were studied in 18 patients. Blood samples were obtained one day after diagnosis (day 1) and, in 11 patients, also on the fourth and tenth days after diagnosis (days 4 and 10). On day 1, patients showed laboratory signs of haemostatic alterations such as positive fibrinogen/fibrin degradation products, and increased thrombin:antithrombin-III (TAT) complex levels. Compared with the control group, patients on day 1 had significantly decreased (p < 0.001) antigenic protein C (69 +/- 28%) and protein C inhibitor (PCI) (33 +/- 22%) whereas a significant increase in the levels of activated protein C (APC) complexed with alpha 1-antitrypsin (alpha 1AT) (APC:alpha 1AT, 26 +/- 15 ng/mL) and APC:PCI complex (3.0 +/- 2.0 ng/mL), and in the level of plasma kallikrein (KK) complexes with PCI (KK:PCI) (31 +/- 22 ng/mL) was observed. There was a positive correlation between APC:alpha 1AT and TAT complex levels (r = 0.597, p = 0.009). In the follow-up a trend toward normal values in antigenic protein C and PCI, and in APC:PCI and KK:PCI complex levels was found. However, PCI remained significantly decreased compared to normal values. C4b-binding protein, alpha 1AT, and TAT and APC:alpha 1AT complexes did not show any significant variations during the course of the disease, suggesting the contribution of the inflammatory and haemostatic responses, in spite of the good recovery of the patients. This study shows that in the course of sepsis, patients experience a generalized activation of the protein C pathway which was more prominent on day 1, resulting in the consumption of protein C and PCI and in the increase of APC:inhibitor complexes. Moreover, these data provide further evidence that KK:PCI circulating complexes occur in vivo.
 ...
PMID:Activation of the protein C pathway in acute sepsis. 749 7

It has been proposed that the reduction in mortality in animal models of sepsis by activated protein C (APC) is mediated by an antiinflammatory property rather than the well-characterized anticoagulant action. Human recombinant APC was examined for potential antiinflammatory activity in the pentobarbital-anesthetized rat. In the dermal reversed passive Arthus model, APC (20.0 mg/kg/h, i.v.) elevated clotting time 10-fold 3 h after the Arthus challenge, at which time, the wet-weights from Arthus dermal samples in APC rats (120.0 +/- 1.5 mg, n = 10) did not differ from controls (120.1 +/- 1.5 mg, n = 10) but were 30% heavier than remote noninflamed skin (92.0 +/- 2.0 mg, n = 10), indicating that APC treatment did not diminish tissue edema associated with immune-complex deposition. Skin-lesion myeloperoxidase (neutrophil marker enzyme) activities from APC rats were not significantly different from controls but was 21-fold more than remote noninflamed skin, indicating that APC treatment did not diminish dermal recruitment of neutrophils. In the intestinal ischemia/reperfusion model, 1 h complete occlusion of the superior mesenteric artery and an additional 4 h reperfusion was associated with a 2.87-fold increase in lung myeloperoxidase activity compared to sham-operated rats. APC (1.0 mg/kg/h, i.v.) did not diminish the elevation in this index of lung neutrophil sequestration. In conclusion, APC did not produce an antiinflammatory effect in the rat models used.
 ...
PMID:Activated recombinant human protein C does not attenuate recruitment of neutrophils in rat models of acute inflammation. 771 66

Haemostatic parameters were studied in 12 adult patients with acute myeloid leukaemia and acute lymphoblastic leukaemia in complete remission using high-dose cytosine arabinoside regiments together with with other drugs. Increased tissue plasminogen activator (t-PA:Ag) antigen 4 hours after AraC application (p < 0.05) as well as increased levels of plasminogen activator inhibitor activity (PAI) (p < 0.05) and fibrinopeptide A (FPA) antigen (p < 0.05) were observed on day 2. All patients during bone marrow aplasia suffered from infectious complications (7 from sepsis and 5 from fever of undetermined origin). During that period of infection the increased levels of FPA on day 21 (p < 0.05), PAI on days 15 and 21 (p < 0.05) and fibrinogen on day 21 (p < 0.05) as well as decreased values of antithrombin III (p < 0.05) on day 21 and protein C on day 15 (p < 0.05) were measured. t-PA:Ag, plasminogen, alpha 2 antiplasmin and fibrin(ogen) degradation products were within normal throughout infectious complications. None of the patients experienced clinically manifest thrombotic complication. Though the results demonstrate that changes found were not clinically important (even if they were statistically significant), and that haemostasis was compensated as well as that thrombosis was not serious problem, authors recommend routine haemostasis monitoring in acute leukaemia patients, especially at diagnosis, in association with chemotherapy and during infectious complications.
 ...
PMID:[Hemostasis in patients with acute leukemia treated with high doses of cytosine-arabinoside: the effect of chemotherapy and infectious complications on hemostasis]. 781 98

The authors present an infant with left ventricular and mitral valve thrombi diagnosed by cross-sectional echocardiography. Thrombosis was due to acquired transient protein C deficiency, which was caused by impaired liver function due to sepsis. Because the thombi were very large and mobile, urgent surgery was performed. Eight weeks later, the patient's protein C level returned to normal ranges. The authors suggest that in all cases with intracardiac thrombosis, protein C deficiency should be investigated.
 ...
PMID:Mitral valve and left ventricular thrombi in an infant with acquired protein C deficiency. A case report. 781 62

The baboon model of E. coli sepsis illustrates three concepts with respect to the host response and vascular endothelium. First, the endothelium is the primary target. E. coli sepsis is an acute inflammatory disease of the vascular endothelium. Second, the endothelium is not a passive target. Initially it regulates both the inflammatory and coagulopathic aspects of E. coli sepsis through membrane associated regulatory receptor/plasma protein assemblies including protein C/thrombomodulin, activated protein C/protein S, C4bBP/protein S, tissue factor pathway inhibitor/Xa, antithrombin III/glycosaminoglycans. Third, when overridden by inflammatory events, the endothelium can change its anticoagulant phenotype and mount a massive procoagulant fibrinolytic counter-attack on its luminal side through the expression of tissue factor and release of tissue plasminogen activator. Fourth, again when overridden by inflammatory events, the endothelium can change its antioxidant phenotype and produce a "distal" tissue hypoxia on its abluminal side through induction of free radical generation and peroxidation of mitochondrial lipid membranes of those tissues with high metabolic rates. It has become increasingly clear that the so-called anticoagulant systems which act on the proximal factors of the clotting cascade (protein C, TFPI, AT-III, PGI2) also attenuate the amplification of the inflammatory response. Aspects of the mechanism by which this occurs are coming to light. This includes the attenuation of Il-6 response by TFPI and the attenuation of the complement effects by C4bBP/PS. The specifics of these observations in the E. coli sepsis model will be reviewed.
 ...
PMID:Studies on the inflammatory-coagulant axis in the baboon response to E. coli: regulatory roles of proteins C, S, C4bBP and of inhibitors of tissue factor. 783 58

This study explored the relationship between cytokines (TNF, IL-1, IL-6), coagulation and fibrinolytic factors in the early stage of sepsis syndrome and the relation between these factors with the severity of inflammatory illness as measured by the Simplified Acute Physiology Score (SAPS). Twenty-one normal controls were compared to 34 patients divided into three categories ranging from uncomplicated postoperative patients, to patients with severe infectious conditions including septic shock. A major hemostatic imbalance was demonstrated with particularly marked reduction in fibrinolytic activity [drop of antithrombin III (ATIII) and protein C with an increase of plasminogen activator inhibitor (PAI-1) levels] which were directly correlated with the severity of the inflammatory state. Both ATIII and PAI-1 levels were correlated with the levels of TNF and IL-6 and the severity of illness as measured by SAPS. We established an index, ATIII/PAI-1 antigen that is significantly different among the four groups (p < 0.001) and strongly correlated with the SAPS (p < 0.001). As PAI-1 could be secreted not only by TNF activating endothelial cells but also by hepatocytes activated by insulinemia, treatment of sepsis with cytokine-specific agents might be of limited effect.
 ...
PMID:Coagulation/fibrinolysis balance in septic shock related to cytokines and clinical state. 795 54

An unusual case of a 67-year-old man is reported with fulminant pneumococcal sepsis. He had been healthy before, and the identified predisposing factors were only that he was a chronic alcohol drinker and was a HCV carrier. He presented signs of acute renal failure, liver dysfunction, adult respiratory distress syndrome and disseminated intravascular coagulation. Subsequently purpura fulminans (symmetrical peripheral gangrene) with major extremity involvement developed. He finally survived with amputation of both legs, right forearm and two fingers of left hand. Purpura fulminans is a rare catastrophic disease, with initial hemorrhagic skin lesions that progress to gangrene. It usually follows an infectious illness, and although it most commonly occurs in children, it can occur in adults with predisposing factors such as alcoholic, asplenia, AIDS and so on. In adults, pneumococcus and meningococcus are microorganisms that have been reported most frequently as caused agents in Europe and America. But in Japan the previously reported adult case was the only one complicating Xanthomonas maltophilia sepsis, and none accompanying pneumococcal sepsis. Congenital protein C deficiency is recognized to be able to cause purpura fulminans especially in patients with risk factors. In our case, protein C antigen was decreased in the acute stage but gradually increased later toward normal, so this decrease was thought to be concomitant with the initial disseminated intravascular coagulation rather than compatible with protein C deficiency.
 ...
PMID:[Purpura fulminans complicating pneumococcal sepsis: a case report]. 796 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>