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)

Infection, mainly related to vascular access, is one of the main causes of morbidity and a preventable cause of death in hemodialysis patients. From January 1994 to April 1998 we conducted a prospective study to assess the incidence and risk factors of catheter-related bacteremia. One hundred and twenty-nine tunneled dual-lumen hemodialysis catheters were inserted percutaneously into the internal jugular vein in 89 patients. Bacteremia (n = 56) occurred at least once with 37 (29%) of the catheters (an incidence of 1.1/1,000 catheter-days); local infection (n = 45, 1/1,000 catheter-days) was associated with bacteremia in 18 cases. Death in 1 case was directly related to Staphylococcus aureus (SA) septic shock, and septicemia contributed to deaths in 2 additional cases. Catheters were removed in 48% of the bacteremic episodes. Treatment comprised intravenous double antimicrobial therapy for 15-20 days. Bacteriological data of bacteremia showed 55% involvement of SA. Nasal carriage of SA was observed in 35% of the patients with catheters. Bacteremic catheters were more frequently observed in patients with diabetes mellitus (p = 0.03), peripheral atherosclerosis (p = 0.001), a previous history of bacteremia (p = 0.05), nasal carriage of SA (p = 0.0001), longer catheter survival time (p = 0.001), higher total intravenous iron dose (p = 0.001), more frequent urokinase catheter infusion (p < 0.01), and local infection (p < 0.001) compared with non-bacteremic catheters. Monovariate survival analysis showed that significant initial risk factors for bacteremia were nasal carriage of SA (p = 0.00001), previous bacteremia (p = 0.0001), peripheral atherosclerosis (p = 0.005), and diabetes (p = 0.04). This study confirms the relatively high incidence of bacteremia with tunneled double-lumen silicone catheters and its potential complications. Possible preventive actions are discussed according to the risk factors.
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PMID:Risk factor analysis for long-term tunneled dialysis catheter-related bacteremias. 1211 69

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

Plasminogen activator inhibitor type 1 (PAI-1) is a 50-kilodalton glycoprotein of the serine protease inhibitor family. The primary role of PAI-1 in vivo is the inhibition of both tissue- and urokinase-type plasminogen activators. In addition to this function, PAI-1 acts as an acute-phase protein during acute inflammation. PAI-1 is a pivotal player in the pathogenesis of sepsis, a complex clinical syndrome that results from a systemic inflammatory response. In patients with sepsis, the levels of PAI-1 are positively related to poor outcome, increased severity of disease, and increased levels of various cytokines, acute-phase proteins, and coagulation parameters. The 4G/5G insertion/deletion promoter polymorphism, which leads to differences in PAI-1 production, has been demonstrated to affect the risk of developing severe complications and dying from sepsis during meningococcal infection and multiple trauma.
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PMID:Plasminogen activator inhibitor type 1 gene polymorphism and sepsis. 1623 47

Metformin [2-(N,N-dimethylcarbamimidoyl)guanidine] is a drug used in the treatment of type 2 diabetes. Recent studies have suggested that metformin may have effects in addition to lowering serum glucose concentrations (e.g., anti-inflammatory). The aim of the present study was to determine whether metformin prevents the inflammatory reaction and liver damage in a model of postsurgical sepsis. Accordingly, rats underwent 2/3 partial hepatectomy (PH; or sham surgery); 48 h after surgery, animals were administered endotoxin (LPS; 1.5 mg/kg i.v.). Both PH and LPS alone caused some minor liver damage. However, their combined effect (PH/LPS) was synergistic, leading to robust hepatic damage, as indicated by plasma enzymes and histological assessment. Although metformin treatment did not alter changes caused by PH alone, it almost completely blunted the effects of LPS in the PH/LPS group. Increases in biomarkers of inflammation (e.g., interleukin 6, interferon gamma, and neutrophil number) were also blunted by metformin treatment. Furthermore, PH/LPS caused a >200x increase in hepatic plasminogen activator inhibitor 1 (PAI-1) mRNA expression and plasma PAI-1 protein. These increases were associated with inhibition of hepatic urokinase plasminogen activator activity and an increase in fibrin deposition, indicative of local thrombosis. These effects were markedly reduced by metformin treatment. In conclusion, these data demonstrate that metformin prevents liver damage in a model of postsurgical sepsis in rats by decreasing proinflammatory and hemostatic responses.
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PMID:Metformin prevents endotoxin-induced liver injury after partial hepatectomy. 1632 56

Plasminogen activator inhibitor type-1 (PAI-1) is a major inhibitor of fibrinolysis by virtue of its capacity to inhibit urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). Systemic inflammation is invariably associated with elevated circulating levels of PAI-1, and during human sepsis plasma PAI-1 concentrations predict an unfavorable outcome. Knowledge about the functional role of PAI-1 in a systemic inflammatory response syndrome is highly limited. In this study, we determined the role of endogenous PAI-1 in cytokine release induced by administration of LPS or staphylococcal enterotoxin B (SEB). Both LPS and SEB elicited secretion of PAI-1 into the circulation of normal wild-type (Wt) mice. Relative to Wt mice, PAI-1 gene-deficient (PAI-1(-/-)) mice demonstrated strongly elevated plasma IFN-gamma concentrations after injection of either LPS or SEB. In addition, PAI-1(-/-) splenocytes released more IFN-gamma after incubation with LPS or SEB than Wt splenocytes. Both PAI-1(-/-) CD4+ and CD8+ T cells produced more IFN-gamma upon stimulation with SEB. LPS-induced IFN-gamma release in mice deficient for uPA, the uPA receptor, or tPA was not different from IFN-gamma release in LPS-treated Wt mice. These results identify a novel function of PAI-1 during systemic inflammation, where endogenous PAI-1 serves to inhibit IFN-gamma release by a mechanism that does not depend on its interaction with uPA/uPA receptor or tPA.
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PMID:Plasminogen activator inhibitor type-1-deficient mice have an enhanced IFN-gamma response to lipopolysaccharide and staphylococcal enterotoxin B. 1711 93

Dual-lumen cuffed central venous catheter proved an important alternative vascular access compared to conventional arteriovenous (Cimino-Brescia) shunt in a selected group of patients on regular dialysis treatment. Typically, these catheters are used as bridging access, until fistula or graft is ready for use, or as permanent access when an arteriovenous fistula or graft is not planned (NKF-DOQI). We conducted a prospective study on IJV permanent catheter insertion and its related earlier and long-term complications. From February 1991 to February 2001 we inserted in 124 patients in end stage renal disease 135 cuffed catheters (130 in the right IJV and 5 in the left IJV), 92 of which were Permcath, 27 Vascath, and 16 Ash-Split. We performed the insertion of catheters by puncturing the IJV under ultrasonographic guid-ance in the lower side of the Sedillot triangle and checking the accurate position of the tip by endocavitary electrocardiography (EC-ECG). The duration of catheter use was from 60 to 1460 days, mean 345 days. The actuarial survival rate at 1 year was 82%, at 2 years 56%, at 3 years 42% and at 4 years 20%. The exit site infection and septicemia rates were 5.2 and 2.86 per 1000 catheter days respectively. Catheter sepsis was implicated in the death of three patients, all of whom had multiple medical problems. Several episodes of thrombosis (6% of dialyses) occurred which required urokinase treatment, and catheter replacement in 12 patients (9.6%). In 3 cases the catheters were displaced and correct repositioning was performed. Two catheters (Ash-Split) were replaced due to accidental damage of the external portion of catheters (alcoholic disinfectant). Catheter tip embolism occurred on one occasion during elective catheter exchange over guide-wire. One of the common problems encountered with cuffed tunneled catheters is poor blood flow, most often secondary to the formation of a fibrin sheath around the lumen. Even if we conducted a non-randomized study, in our experience, the higher rate of malfunctioning catheters was in the group with no anticoagulation therapy. Therefore, we suggest anticoagulation treatment in all patients wearing central vascular catheters with no contraindication. Just one year ago, we followed NKF-DOQI clinical practice guidelines for vascular access that indicated that for patients who have a primary AV fistula maturing, but need im-mediate hemodialysis, tunneled cuffed catheters are the access of choice and the preferred insertion site is the right IJV. Considering recent reports of permanent central venous stenosis or occlusion after IJV can-nulation, currently, our first choice is femoral vein cannulation with smooth silicone rubber catheters, tunneled if long-term utilization is needed (more the 3-4 weeks). In our opinion, the right IJV puncture is to be avoided as much as the venipuncture of arm veins suitable for vascular access placement, particularly the cephalic vein of the non-dominant arm. Our data confirm that permanent venous catheters might rep-resent an effective long-term vascular access for chronic hemodialysis, particularly for older patients with cardiovascular disease and for cancer patients.
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PMID:Implantation of permanent jugular catheters in patients on regular dialysis treatment: ten years' experience. 1763 64

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.
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PMID:Identification of diagnostic biomarkers for infection in premature neonates. 1862 29

Anthrax is a zoonotic disease caused by Bacillus anthracis. The infection is associated with inflammation and sepsis, but little is known about the acute-phase response during disease and the nature of the bacterial factors causing it. In this study, we examined the levels of the acute-phase proteins (APPs) in comparative experiments using mice challenged with spores and a purified B. anthracis protease InhA as a possible factor mediating the response. A strong increase in the plasma levels of APPs such as haptoglobin and serum amyloid A was observed during infection. Protein and mRNA levels of plasminogen activator inhibitor (PAI)-1 in the liver were also increased concurrently with bacterial dissemination at 72 h post-infection. Similar effects were observed at 6 h post injection with InhA. Induction of hepatic transforming growth factor-beta1, a PAI-1 inducer, was also found in the liver of InhA-injected mice. PAI-1 elevation by InhA resulted in an increased level of urokinase-type plasminogen activator complex with PAI-1 and a decreased level of D-dimers indicating inhibition of blood fibrinolysis. These results reveal an acute liver response to anthrax infection and provide a plausible pathophysiological link between the host inflammatory response and the pro-thrombotic haemostatic imbalance in the course of disease through PAI-1 induction in the liver.
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PMID:Activation of plasminogen activator inhibitor implicates protease InhA in the acute-phase response to Bacillus anthracis infection. 1942 49

Early onset sepsis due to group B streptococcus leads to neonatal morbidity, increased mortality, and long-term neurological deficencies. Interaction between septicemic GBS and confluent monolayers of human coronary artery endothelial cells (HCAECs) was analyzed by genome wide expression profiling. In total, 124 genes were differentially expressed (89 upregulated, 35 downregulated) based on a more than 3-fold difference to control HCAEC. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, infection, and inflammation. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real-time RT-PCR assay (granulocyte chemotactic protein 2), ELISA (urokinase, cyclooxygenase 2, granulocyte chemotactic protein 1), and western blotting (Heme oxygenase1, BCL2 interacting protein) at various time points between 4 and 24 hours. These results indicate that GBS infection might influence signalling pathways leading to impaired function of the innate immune system and hemorrhagic and inflammatory complications during GBS sepsis.
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PMID:Infection of human coronary artery endothelial cells by group B streptococcus contributes to dysregulation of apoptosis, hemostasis, and innate immune responses. 2143 10

The study by Yang and colleagues examined 81 patients with septic shock due to pneumonia, along with 20 patients with pneumonia without organ dysfunction. Their major findings were that circulating levels of soluble vascular endothelial cell growth factor receptor-1 (sVEGFR-1) and urokinase-type plasminogen activator (uPA) were associated with organ dysfunction and mortality, whereas vascular endothelial cell growth factor (VEGF) levels had no such predictive power. Yang and colleagues are to be complimented for a well-conducted study of a reasonably (and helpfully!) homogeneous population of patients with sepsis that carefully and comprehensively analyzed the relationship between sVEGFR-1, uPA, VEGF and clinical outcome. The study serves not only to provide evidence in support of new diagnostic biomarker targets in sepsis, but also to augment the growing evidence of an important role of the endothelium in sepsis in general, and the VEGF signaling axis in particular.
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PMID:Sepsis and the broken endothelium. 2121 33


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