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)

Clinical studies have demonstrated that chronic alcohol abuse is an independent outcome variable in acute lung injury. The Emory Center for the Study of Acute Lung Injury is determining the mechanisms by which ethanol increases susceptibility to acute lung injury. We developed a rat model of chronic ethanol ingestion and demonstrated that ethanol predisposes rats to edematous lung injury elicited by endotoxemia or sepsis. Chronic ethanol ingestion in rats led to decreased levels of glutathione, an important antioxidant in the lung, and this defect was associated with alterations in epithelial cell permeability, decreased alveolar liquid clearance, decreased cell viability, and decreased surfactant production. Chronic ethanol ingestion also led to the activation of lung tissue remodeling as demonstrated by the increased expression of profibrotic growth factors, matrix components, and metalloproteases. In cultured fibroblasts, the induction of the matrix glycoprotein fibronectin by ethanol was mediated via nicotinic acetylcholine receptor-dependent signal transduction. We speculate that these alterations render the host susceptible to acute lung injury by diminishing the protective mechanisms of the lung and promoting exaggerated inflammatory and tissue repair responses elicited against injurious agents.
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PMID:Chronic ethanol ingestion increases susceptibility to acute lung injury: role of oxidative stress and tissue remodeling. 1247 7

Vibrio vulnificus is the leading cause of death in the United States associated with the consumption of raw seafood, particularly oysters. In epidemiological studies, primary septicemia and inflammation-mediated septic shock caused by V. vulnificus is strongly associated with liver disease, often in the context of chronic alcohol abuse. The present study was undertaken to determine whether clinical biomarkers of liver function or cellular oxidative stress are associated with peripheral blood mononuclear cell inflammatory cytokine responses to V. vulnificus. Levels of interleukin-1 beta (IL-1 beta), IL-6, IL-8, and tumor necrosis factor alpha elicited in response to V. vulnificus and measured in cell supernatants were not associated with the liver biomarkers aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or the AST/ALT ratio. In contrast, reduced glutathione (GSH) levels were associated with the release of all four cytokines (IL-1 beta [R(2) = 0.382; P = 0.006], IL-6 [R(2) = 0.393; P = 0.005], IL-8 [R(2) = 0.487; P = 0.001], and TNF-alpha [R(2) = 0.292; P = 0.021]). Those individuals with below-normal GSH levels produced significantly less proinflammatory cytokines in response to V. vulnificus. We hypothesize that persons with markers for cellular oxidative stress have increased susceptibility to V. vulnificus septicemia.
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PMID:Inflammatory cytokine response to Vibrio vulnificus elicited by peripheral blood mononuclear cells from chronic alcohol users is associated with biomarkers of cellular oxidative stress. 1281 21

Chronic alcohol abuse increases the risk of developing acute lung injury approximately threefold in septic patients, and ethanol ingestion for 6 wk in rats impairs alveolar epithelial barrier function both in vitro and in vivo. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a trophic factor for the alveolar epithelium, and a recent phase II clinical study suggests that GM-CSF therapy decreases sepsis-mediated lung injury. Therefore, we hypothesized that GM-CSF treatment could improve ethanol-mediated defects in the alveolar epithelium during acute stresses such as endotoxemia. In this study, we determined that recombinant rat GM-CSF improved lung liquid clearance (as reflected by lung tissue wet:dry ratios) in ethanol-fed rats anesthetized and then challenged with 2 ml of saline via a tracheostomy tube. Furthermore, GM-CSF treatment improved lung liquid clearance and decreased epithelial protein leak in both control-fed and ethanol-fed rats after 6 h of endotoxemia induced by Salmonella typhimurium lipopolysaccharide given intraperitoneally, but with the greater net effect seen in the ethanol-fed rats. Our previous studies indicate that chronic ethanol ingestion decreases lung liquid clearance by increasing intercellular permeability. Consistent with this, GM-CSF treatment in vitro decreased permeability of alveolar epithelial monolayers derived from both control-fed and ethanol-fed rats. As in the endotoxemia model in vivo, the effect of GM-CSF was most dramatic in the ethanol group. Together, these results indicate that GM-CSF treatment has previously unrecognized effects in promoting alveolar epithelial barrier integrity and that these salutary effects may be particularly relevant in the setting of chronic alcohol abuse.
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PMID:Granulocyte/macrophage colony-stimulating factor treatment improves alveolar epithelial barrier function in alcoholic rat lung. 1450 66

Chronic alcohol abuse is of significant clinical and economic relevance. A major part of internal medical pathology is associated with chronic alcoholism. 50% of all accidents with subsequent traumatic injuries are related to alcohol intake. Patients who are chronic alcohol abusers have prolonged hospital stays and substantial increases in postoperative morbidity. A sophisticated diagnosis of alcoholism within standard clinical routine is often difficult, and in most cases the treatment of alcohol-related diseases and complications is protracted and requires increased energy expenditure by the treating physicians. In surgical patients, chronic alcohol abuse is associated with a 3- to 4-fold risk of infections, sepsis, cardiac and bleeding complications. Therefore, the patients themselves, along with the general practitioner and an in-hospital interdisciplinary team should cooperate in medical and operative treatment in order to attain better clinical outcome. Each patient history should include a detailed assessment of the quantity of daily alcohol intake. Alcoholic diagnostic regimens including questionnaires (i.e. CAGE, AUDIT) in combination with specific laboratory markers (CDT, GGT, MCV), if implemented, could prove valuable, especially in cases where major surgical procedures are considered. Strict abstinence by alcoholic patients with organ pathology in medical and elective surgical settings as well as the prophylactic treatment of pre-operative alcohol withdrawal appear to be useful strategies to reduce the risk of complications. Short-term interventions are associated with reduced alcohol intake and decreased incidence of re-trauma. Considering the clinical relevance of alcohol abuse, sufficient screening, interventions, and open approaches to address alcohol problems should be important components of the daily clinical routine in outpatient clinics, emergency rooms, in GPs' offices and in general hospitals.
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PMID:[The alcoholic patient in the daily routine]. 1460 33

Marginal liver donor criteria included the following: obesity (weight >100 Kg or BMI >27), age >50 years; macrovesicular steatosis >50%; intensive care unit stay >4 days; prolonged hypotensive episodes of >1 hour, and <60 mm Hg with high inotropic drug use (dopamine, [DPM] > 14 microg/kg per minute); cold ischemia time >14 hours, peak serum sodium >155 mEq/L; sepsis, viral infections, and alcoholism; high levels of bilirubin, ALT, and AST, or extrahepatic neoplasia. Between August 1992 and May 2003, we performed 251 liver transplants in 241 patients of whom 155 are presently alive. We used 124 (49.4%) standard donors and 127 (50.6%) marginal donors. Among the group that received a standard donor, 81 (65.3%) are still alive. Among recipients of organs from marginal donors. 81 (63.8%) are still alive. We also assessed the quality of donors according to the severity of recipient disease. For standard donors these outcomes were 61.5% for UNOS 1, 37.5% for UNOS 2A, 73.2% for UNOS 2B, and 80% for UNOS 3 for marginal donors they were 46.1% for UNOS 1, 53.6% for UNOS 2A, 70.7% for UNOS 2B, and 63.6% for UNOS 3. Among the patients who received a liver from a donor >60 years old, there were no survivors in UNOS 1 and 2A, but there were good results in groups 2B and 3. These results suggest there is no difference between marginal and standard donors, even in sick patients, with the exception of donor age.
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PMID:Marginal donors in liver transplantation. 1511 May 80

Endotoxin (lipopolysaccharide, LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release from Kupffer cells is critically involved in the pathogenesis of alcohol-induced liver injury. We recently reported that inhibition of alcohol-induced plasma endotoxin elevation contributes to the protective action of zinc against alcoholic hepatotoxicity. The present study was undertaken to determine whether zinc interferes with the endotoxin-TNF-alpha signaling pathway, and possible mechanism(s) by which zinc modulates the endotoxin-TNF-alpha signaling. Administration of LPS to metallothionein (MT)-knockout (MT-KO) mice and 129/Sv wild-type (WT) controls at 4 mg/kg induced hepatic TNF-alpha elevation at 1.5 hours, followed by liver injury at 3 hours. Zinc pretreatment (two doses at 5 mg/kg) attenuated TNF-alpha production and liver injury in both MT-KO and WT mice, indicating a MT-independent action of zinc. Immunohistochemical detection of the phosphorylation of I-kappaB and nuclear factor (NF)-kappaB in the liver of MT-KO mice demonstrated that zinc pretreatment abrogated LPS-induced NF-kappaB activation in the Kupffer cells. Fluorescent microscopy of superoxide by dihydroethidine and of zinc ions by Zinquin in the liver of MT-KO mice showed that zinc pretreatment increased the intracellular labile zinc ions and inhibited LPS-induced superoxide generation. These results demonstrate that zinc inhibits LPS-induced hepatic TNF-alpha production through abrogation of oxidative stress-sensitive NF-kappaB pathway, and the action of zinc is independent of MT. Thus, zinc may be beneficial in the treatment of LPS-induced liver injuries, such as sepsis and alcoholism.
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PMID:Abrogation of nuclear factor-kappaB activation is involved in zinc inhibition of lipopolysaccharide-induced tumor necrosis factor-alpha production and liver injury. 1511 1

Because chronic alcohol abuse alters immune defenses and increases infection in adults, we tested the hypothesis that maternal alcohol use during pregnancy would increase the risk of sepsis in very low birth weight (VLBW) premature newborns. We performed a case-controlled analysis of VLBW newborns born at Grady Memorial Hospital (Atlanta, GA). Alcohol exposure, as the predictive variable, was assessed by maternal self-report. The outcome variables were early-onset and multiple late-onset sepsis. Univariate analysis with Fisher exact test and multivariate analysis with the use of binary logistic regression were performed. Early-onset sepsis was 15-fold higher in the alcohol-exposed group (n=20) compared with findings for the matched control group (n=168) [alcohol-exposed group, 10%, vs. control group, 0.6%: odds ratio (OR) 6.8 (95% confidence interval [CI], 2.7-17.1), P < or = .05]. Early-onset sepsis in the alcohol+cocaine-exposed group (n=64) did not differ from findings for the control group. The prevalence of multiple late-onset sepsis did not differ among the exposure groups. Logistic regression analysis, controlling for chorioamnionitis and premature prolonged rupture of membranes, demonstrated an independent, increased risk of early-onset sepsis with alcohol exposure [OR 16 (95% CI, 1.2-210), P < or = .05]. We conclude that alcohol exposure significantly increased the risk of early-onset sepsis in this group of VLBW newborns. The effects of maternal alcohol abuse during pregnancy on the risk of infection in the VLBW newborn require further analysis.
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PMID:Is maternal alcohol use a risk factor for early-onset sepsis in premature newborns? 1552 11

This author has personally carried out in excess of 700 major hepatic resections for tumor, and runs a unit with a current resection rate of 200 per year, yet uses no scientific tests designed to judge hepatic reserve. In our unit, we have an advantage in that we deal with a northern European population, with a low rate of viral hepatitis, although alcoholism is becoming an increasing feature within our practice and we are dealing with more elderly patients that in the past, and more who have undergone neoadjuvant chemotherapy. In these patients, there appear to be greater risks of postoperative sepsis and slower regeneration. Approximately 65% of our current resection practice is hemihepatectomy or more and the majority is trisectionectomy (extended hepatectomy) and bilateral resection work. Preoperative, operative, and postoperative factors affect the occurrence of postoperative hepatic failure and these aspects are considered. Case series studies are presented to illustrate the incidence of significant hepatic failure we have encountered.
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PMID:Assessment of hepatic reserve for the indication of hepatic resection: how I do it. 1575 92

This study of ventilated patients investigated pneumonia risk factors and outcome predictors in 476 episodes of pneumonia (48% community-acquired pneumonia, 24% hospital-acquired pneumonia, 28% ventilator-associated pneumonia) using a prospective survey in 14 intensive care units within Australia and New Zealand. For community acquired pneumonia, mortality increased with immunosuppression (OR 5.32, CI 95% 1.58-1799, P<0.01), clinical signs of consolidation (OR 2.43, CI 95% 1.09-5.44, P=0.03) and Sepsis-Related Organ Failure Assessment (SOFA) scores (OR 1.19, CI 95% 1.08-1.30, P<0.001) but improved if appropriate antibiotic changes were made within three days of intensive care unit admission (OR 0.42, CI 95% 0.20-0.86, P=0.02). For hospital-acquired pneumonia, immunosuppression (OR 6.98, CI 95% 1.16-42.2, P=0.03) and non-metastatic cancer (OR 3.78, CI 95% 1.20-11.93, P=0.02) were the principal mortality predictors. Alcoholism (OR 7.80, CI 95% 1.20-17.50, P<0.001), high SOFA scores (OR 1.44, CI 95% 1.20-1.75, P=0.001) and the isolation of "high risk" organisms including Pseudomonas aeruginosa, Acinetobacter spp, Stenotrophomonas spp and methicillin resistant Staphylococcus aureus (OR 4.79, CI 95% 1.43-16.03, P=0.01), were associated with increased mortality in ventilator-associated pneumonia. The use of non-invasive ventilation was independently protective against mortality for patients with community-acquired and hospital-acquired pneumonia (OR 0.35, CI 95% 0.18-0.68, P=0.002). Mortality was similar for patients requiring both invasive and non-invasive ventilation and non-invasive ventilation alone (21% compared with 20% respectively, P=0.56). Pneumonia risks and mortality predictors in Australian and New Zealand ICUs vary with pneumonia type. A history of alcoholism is a major risk factor for mortality in ventilator-associated pneumonia, greater in magnitude than the mortality effect of immunosuppression in hospital-acquired pneumonia or community-acquired pneumonia. Non-invasive ventilation is associated with reduced ICU mortality. Clinical signs of consolidation worsen, while rationalising antibiotic therapy within three days of ICU admission improves mortality for community-acquired pneumonia patients.
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PMID:Disease risk and mortality prediction in intensive care patients with pneumonia. Australian and New Zealand practice in intensive care (ANZPIC II). 1595 85

The annual incidences of severe sepsis in several industrialized nations have recently been reported to be 50-100 cases per 100,000 persons. These numbers exceed the estimated rates for other diseases that hold a heightened public awareness, including breast cancer and acquired immune deficiency syndrome. There are also sex and race differences in the incidence of sepsis. Men are more likely than women to develop sepsis, with a mean annual relative risk of 1.28. Nonwhites are nearly twice as likely to develop sepsis as whites. These race and sex disparities in the incidence of sepsis are likely explained by differences in a variety of factors, including the presence of comorbid conditions. For example, chronic alcohol abuse is associated with a persistent fever, delayed resolution of symptoms, increased rates of bacteremia, increased use of intensive care, prolonged duration of hospital stay, and increased cost of hospitalization for infected patients.
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PMID:Epidemiology of sepsis: race, sex, and chronic alcohol abuse. 1623 52


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