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)

Activated macrophages convert L-arginine to citrulline and unstable nitrogen oxides that have cytotoxic properties. We recently have shown that the inhibition of protein synthesis in Kupffer cell (KC):hepatocyte (HC) coculture, following exposure to gram-negative bacterial endotoxin (lipopolysaccharide), is due to the metabolism of L-arginine by this cytotoxic pathway. Although this finding supports a role for activated KCs and the L-arginine-dependent mechanism in the HC dysfunction seen in sepsis, it and previous studies have failed to demonstrate direct damage to HCs by adjacent KCs. The current study was undertaken to determine if KCs exposed to lipopolysaccharide could directly damage HCs and, if so, whether the damage was dependent on the metabolism of L-arginine. By using the release of aspartate aminotransferase as a marker of HC damage, it was found that a significant aspartate aminotransferase release by KC:HC cocultures in response to lipopolysaccharide occurred only if L-arginine was present. In addition, requirements for significant aspartate aminotransferase release included KC:HC ratios of 7.5:1 or greater and L-arginine concentrations of 1 mmol or more. Although the KC-induced damage was mild, these results show that in vitro HC damage in KC:HC coculture does require the metabolism of L-arginine and supports a hypothesis that toxic L-arginine metabolites may contribute to liver cell damage in patients with sepsis.
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PMID:Kupffer cell cytotoxicity to hepatocytes in coculture requires L-arginine. 258 66

Abnormalities in biochemical liver function tests in 127 general surgical patients who had a course of intravenous nutrition have been reviewed. Only 26 patients had liver function tests considered to be normal on commencing intravenous nutrition and they were included in this retrospective study. During intravenous nutrition the most sensitive biochemical test of liver dysfunction was gamma-glutamyl transpeptidase--all patients having an elevated gamma-glutamyl transpeptidase level by week 4. Most abnormalities were transient whereas the elevation of alkaline phosphatase was prolonged beyond week 9. Patients with major sepsis were found to have almost double the incidence of abnormal liver function test values compared with patients with no evidence of sepsis. Only patients who were transfused more than 8 units of blood showed a significant rise in bilirubin. Liver function tests in patients who received smaller transfusions showed no difference from patients who did not receive any blood. Patients with below normal anthropometric measurements on commencing intravenous nutrition were more likely to develop abnormalities in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase.
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PMID:Intravenous nutrition and hepatic dysfunction. 287 Feb 3

Acute cholangitis complicating diagnostic endoscopic retrograde cholangiopancreatography (ERCP) is potentially fatal. Among 323 consecutive patients with proved biliary obstruction, 21 (7 percent) developed acute cholangitis after examination. Four patients underwent emergency surgery for the control of sepsis with two deaths. Of the 21 parameters chosen for evaluation, malignant obstruction, fever (higher than 37.5 degrees C) within 72 hours before the procedure or when afebrile, and an increased aspartate transaminase level of 70 IU or more were the independent predictive factors identified by multivariate analysis. An increased temperature should be regarded as an absolute contraindication to examination unless followed by immediate ductal drainage. Since the risk of septic complications is minimal when none of the risk factors are present, routine urgent biliary decompression after ERCP is probably unnecessary for these selected patients. For patients with malignant obstruction or other risk factors, early elective surgical drainage is advisable. When surgery is not feasible, nonoperative drainage of the obstructed biliary system as a preventive measure might be considered.
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PMID:Urgent biliary decompression after endoscopic retrograde cholangiopancreatography. 291 Jan 17

We evaluated the concept that the vascular entrance of both bacterial and nonbacterial particulate material could lead to hepatic parenchymal cell injury, either due to postphagocytic Kupffer cell activity or the margination of activated leukocytes in the liver. Injection of denatured, collagen-coated particles as well as heat-killed bacteria were used as particulate challenges. Hepatic parenchymal cell injury in vivo during postoperative sepsis was evaluated by plasma aspartate aminotransferase (AST) and ornithine carbamyl transferase (OCT) enzyme levels over 3-72 h. AST and OCT levels elevated following either laparotomy plus cecal ligation (mild sepsis) or laparotomy plus cecal ligation with puncture (severe sepsis), with the peak level at 24 h. In addition, the direct intravenous injection of either nonbacterial foreign particles or heat-killed Pseudomonas aeruginosa into normal rats also produced a dose-dependent elevation of AST and OCT. The plasma level of either AST or OCT actually increased 350-400% after injection of the non-bacterial particles. A similar dose related elevation in enzymes followed the intravenous injection of heat-killed Pseudomonas. To differentiate the potential contribution of activated hepatic Kupffer cells versus activated marginated neutrophils to the in vivo hepatic injury, we determined the release of the hepatic specific enzyme OCT by cultured hepatic parenchymal cells when they were exposed to isolated Kupffer cells or isolated PMNs that were activated by exposure to dead bacteria. Bacteria alone when added to cultured hepatocytes did not induce significant OCT release. In contrast, activated PMNs but not Kupffer cells induced a significant (p less than 0.05) release of OCT from parenchymal cells into the culture media. Thus, in vivo transient hepatic parenchymal cell injury with post-operative sepsis may be mediated by the margination of activated PMNs in the liver.
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PMID:Hepatocyte injury during post-operative sepsis: activated neutrophils as potential mediators. 342 80

A total of 466 patients were treated with cefoperazone. The drug was usually administered by drip infusion of 2 to 4 gm/day. Therapy was described as markedly effective and moderately effective in 64 of 77 patients (83.1%) treated for urinary tract infections; 253 of 316 patients (80.1%) treated for respiratory infections; 37 of 48 patients (77.1%) treated for liver biliary duct infections; ten of 16 patients (62.5%) treated for septicemia; and seven of nine patients (77.8%) being treated for other infections. Overall, cefoperazone was effective 79.6% of all patients treated. With respect to bacteriological activity, the overall eradication rate for gram-negative organisms (including Pseudomonas aeruginosa, Klebsiella sp, Escherichia coli, Haemophilus influenzae, Enterobacter sp, and Proteus sp) was 81% (182/225) and for gram-positive (Staphyloccocus aureus, Streptococcus pneumoniae and Streptococcus faecalis) 90% (36/40). Of 205 patients who failed to respond to previous antibiotic therapy, 67.8% were treated effectively with cefoperazone. Side effects, such as skin eruption, pyrexia and diarrhea, occurred in only 4.8% of patients treated, while laboratory abnormalities, such as elevated glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, alkaline phosphatase, and eosinophil values, occurred in only 6.4% of the treated patients. None of these abnormal values were of clinical significance.
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PMID:Clinical trials with cefoperazone in the field of internal medicine in Japan. 644 92

To assess the prevalence and long-term impact of HCV on kidney transplant recipients, we assayed 716 pre-transplant sera using a first-generation ELISA. The anti-HCV positive sera were confirmed by a 6-antigen radioimmunoassay (RIA). Patients were followed up for 5 years. Graft survival, function, evidence of chemical hepatitis (AST > 2x normal), patient mortality and cause of death were evaluated. The prevalence of anti-HCV antibody was 10.3%. In the 638 patients who were followed up for 5 years, there were no differences in graft function, graft survival, overall mortality, or death from sepsis or liver disease. Peak AST levels were significantly higher in anti-HCV positive patients compared to anti-HCV negative patients. At 5 years, the AST levels remained significantly higher in the anti-HCV positive group, however, this was only 6 U/1 > normal. Liver biopsies performed 3 to 7 years post-transplant in 80% of anti-HCV positive patients with chemical hepatitis showed 12% CAH, 50% mild hepatitis and 38% normal histology. Six (9.7%) patients seroconverted from anti-HCV positive to anti-HCV negative 2 to 5 years post-transplant. The presence of anti-HCV does not appear to alter long-term patient or graft survival, and histologic evidence of severe chronic liver disease was rare in anti-HCV positive patients with chemical hepatitis. From these results, the presence of anti-HCV antibody should not preclude kidney transplantation.
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PMID:Long-term outcome in kidney transplant patients with hepatitis C (HCV) infection. 759

The prognostic value of a dynamic liver-function test, based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX), in predicting multiple organ failure (MOF) was prospectively investigated in 28 critically ill patients after multiple trauma. The MEGX test and conventional static liver tests (bilirubin, aspartate aminotransferase, glutamate dehydrogenase, and factor V) were performed on days 1, 3, 5, and 7 after trauma. Patients were classified by a modified MOF score into a group without (n = 18) and a group with the MOF syndrome (n = 10). One patient who developed MOF on the basis of a bacterial septicemia was excluded from the general evaluation. No significant differences were observed in the MEGX values of the two groups on day 1. All patients who subsequently developed MOF, however, displayed a sharp decrease in their MEGX values between days 1 and 3. Analysis of the data using receiver operating characteristic (ROC) curves revealed that the results of the MEGX test on day 3 provided the greatest discriminating power between patients with and without subsequent MOF. A cut-off MEGX value of 30 micrograms/L on day 3 was associated with a prognostic sensitivity of 89% and a prognostic specificity of 94%.
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PMID:Monoethylglycinexylidide as an early predictor of posttraumatic multiple organ failure. 762 99

Liver injury is common in patients following hemorrhage and sepsis. There are multiple etiologies for this liver injury which involve both decreased nutrient blood flow and direct cellular injury. Enteral nutrients vasodilate gut blood vessels and increase blood flow to the intestines and liver. Since enteral nutrients vasodilate gut blood vessels, we wondered whether luminal nutrition would prevent hepatic injury during shock states. We randomized Sprague-Dawley rats to saline or enteral nutrition via duodenal feeding tubes. Animals were then subjected to 60 min of hemorrhagic hypotension or intraperitoneal injection of lipopolysaccharide (LPS). Liver injury was assessed by measuring levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) before and after hemorrhage or LPS. Enteral nutrients significantly decreased liver injury following hemorrhage. AST increased from 246 +/- 17 to 1605 +/- 593 U/L in saline animals and 283 +/- 39 to 551 +/- 94 U/L in enterally fed animals. ALT increased from 60 +/- 4 to 726 +/- 355 U/L in saline animals and 61 +/- 6 to 161 +/- 38 U/L in enterally fed animals. Enteral nutrients did not significantly alter the increase in AST/ALT following LPS. These results indicate that enteral nutrients can decrease liver injury following hemorrhagic hypotension.
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PMID:Enteral feeding minimizes liver injury during hemorrhagic shock. 774 61

Shortage of donor livers has led several liver transplant centres to widen their definition of liver donor suitability. We have assessed the function of liver grafts from "marginal" donors and attitudes to use of such organs. Over an 18-month period, livers used in 30 of 213 consecutive liver transplantations in Birmingham, UK, came from marginal donors (history of alcoholism, abnormal liver function test results, drug overdose that included paracetamol, advanced cardiovascular disease, sepsis, lengthy hypotension [systolic blood pressure < 80 mm Hg for > 1 h], high-dose inotropic drug use). 16 of these donors had been refused by other UK liver transplant centres, 11 on medical grounds. The controls were grafts retrieved from "good" donors (n = 183) during the same period. All 30 grafts showed satisfactory early function but had greater day 1 (p = 0.004) and peak serum aspartate aminotransferase (p = 0.0008) values than control grafts. Graft and patient survival at 1 year in the two groups was similar (72% vs 73% and 80% vs 82%, respectively). To assess attitudes to marginal donor livers, a questionnaire outlining the details of these 30 donors was sent to the 80 centres in the European Liver Transplant Group, and 60 replied. Median immediate refusal rate of the marginal donors was 7/30 (range 0-18) and median outright acceptance rate was only 11/30 (1-26). Larger centres were less selective, with a significantly lower refusal rate (p = 0.03). These results indicate that, because of existing liver donor criteria within Europe, usable donor livers are being unnecessarily refused on medical grounds.
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PMID:Policies in Europe on "marginal quality" donor livers. 796 24

Nitric oxide (NO) and prostaglandins (PG) both possess the ability to induce vasodilatation and prevent the aggregation of platelets. The synthesis of these substances is increased following in vivo lipopolysaccharide (LPS) infusion, but their function during sepsis is incompletely understood. We studied the role of NO and PG in a murine model of chronic hepatic inflammation (Corynebacterium parvum injection), which is known to progress to sudden hepatic necrosis after LPS injection. NO synthesis, which is induced in hepatocytes by C. parvum treatment and in nonparenchymal cells by LPS treatment, was inhibited using NG-monomethyl-L-arginine (L-NMMA). High-dose aspirin (ASA) was used to block PG synthesis. Treatment with L-NMMA or ASA alone, in the absence of LPS, resulted in no increase in hepatic injury. C. parvum-treated mice that received both L-NMMA and ASA without LPS developed marked hepatic damage as reflected by increased hepatocellular enzyme release (aspartate aminotransferase and L-ornithine carbamoyl-transferase). Marked hepatic damage was seen after LPS administration, and ASA pretreatment alone had no effect on the LPS-induced hepatic injury, whereas L-NMMA markedly increased the hepatic damage. The combination of L-NMMA and ASA after LPS resulted in the greatest hepatocellular enzyme release, characterized histologically by intravascular thrombosis with diffuse infarction and necrosis. Simultaneous treatment with either PGI2 or L-arginine partially prevented this injury. These data demonstrate that NO and PG function synergistically to maintain hepatocellular integrity; thus increased synthesis of these mediators protects the liver from the pathophysiological effects of LPS in this model.
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PMID:Nitric oxide and prostaglandins interact to prevent hepatic damage during murine endotoxemia. 802 33


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