Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ceforanide, a new cephalosporin antibiotic with a long half-life (3 h), can be administered twice daily. We evaluated its antimicrobial activity, pharmacology, and clinical efficacy. Twenty-seven patients with infections due to susceptible organisms received ceforanide, 0.5, 1, or 2 g, intramuscularly or intravenously every 12 h for 6 to 28 days. In vitro studies with the clinical isolates from 27 patients treated plus 263 additional isolates showed that ceforanide was active against cephalothin-susceptible gram-positive and gram-negative microorganisms. In addition, ceforanide inhibited 65% of cephalothin-resistant Escherichia coli and 65% of Enterobacter spp. at </=12.5 mug/ml. After a single 1-g intramuscular dose, the mean peak plasma concentration at 1 h was 48.9 mug/ml and that at 12 h was 4.7 mug/ml. Plasma accumulation occurred in some patients. The infections included 10 pneumonias, 3 with bacteremia and 1 with empyema; 11 soft tissue infections, 4 with abscesses and 3 with sepsis; and 3 urinary tract infections. One case each of endocarditis, osteomyelitis, and septic thrombophlebitis, all due to Staphylococcus aureus, were treated. Clinical response was satisfactory in all patients; bacteriological response was satisfactory in 26 of 27 patients. Ceforanide was well tolerated. Three patients developed mild increases in liver enzymes, and one developed slight eosinophilia. In another case, the antibiotic was discontinued because of a fivefold rise in serum glutamic-oxalacetic transaminase (aspartate aminotransferase) and serum glutamic-pyruvic transaminase (alanine aminotransferase) and a twofold rise in lactic acid dehydrogenase and alkaline phosphatase.
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PMID:Ceforanide: in vitro and clinical evaluation. 50 95

1. The hepatic metabolism of glutamine, alanine, ammonia, urea, glutathione and glucose was studied in rats made septic by caecal ligation and puncture and was compared with that in rats that had undergone sham operation (laparotomy). 2. Sepsis resulted in increases in the plasma activities of gamma-glutamyltransferase (P less than 0.001), alanine aminotransferase (P less than 0.001) and aspartate aminotransferase (P less than 0.001), the serum total and direct bilirubin concentrations (P less than 0.001), and the blood lactate (P less than 0.01), glutamine (P less than 0.05), alanine (P less than 0.001) and urea (P less than 0.05) concentrations, but produced decreases in the blood ketone body (P less than 0.001) and glutathione (P less than 0.05) concentrations and in the plasma cholesterol concentration (P less than 0.05). These changes were associated with marked negative nitrogen balance in septic rats. 3. Sepsis increased total hepatic blood flow (by 22.7%) together with hepatic arterial flow (by 25.8%) and portal venous flow (by 18.7%). Sepsis resulted in marked increases in the net rates of hepatic extraction of glutamine (by 164%), alanine (by 138%) and ammonia (by 259%) with concomitant increases in the net rates of hepatic release of glutamate (by 105%), glutathione (by 87.5%), glucose (by 70.1%) and urea (by 100.4%). 4. Sepsis increased the activities of liver carbamoylphosphate synthase (by 16.4%), ornithine transcarbamylase (by 29.8%), argininosuccinate synthase (by 28.1%) and arginase (by 33.8%). 5. Septic rats exhibited marked increases in hepatic protein (by 46.0%), RNA (by 43.4%) and DNA (by 37.7%) contents. These changes were accompanied by marked increases in the activity of thymidine kinase (by 35.9%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic glutamine metabolism in the septic rat. 137 98

We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.
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PMID:University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial. 173 83

A 5-year prospective study was performed to monitor liver function tests (LFTs) in patients receiving total parenteral nutrition (TPN). A gradual and progressive rise was seen in the plasma concentration of bilirubin, aspartate transaminase, and alkaline phosphatase. The rate of rise was not increased in patients with LFT abnormalities before the start of TPN. Half of the patients had an episode of sepsis during TPN, but overall abnormal LFTs did not appear more common in these patients than in those without obvious sepsis. Patients with malignant disease, those requiring long-term TPN, and those requiring a nonstandard TPN regimen were more likely to develop raised LFTs.
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PMID:Liver function tests in patients receiving parenteral nutrition. 190 Nov 8

Sixteen patients with massive bowel resection receiving long-term home total parenteral nutrition (HTPN) for 31 to 145 months were reviewed for evidence of liver disease. Patients were divided into three groups: group 1 with duodenocolostomy (n = 3), group 2 with an estimated 15-43 cm residual small bowel (n = 7), and group 3 with an estimated 55-120 cm residual small bowel (n = 6). Two patients in group 1 developed liver cirrhosis; one was diabetic and died of sepsis and liver failure at the 88th month on HTPN; the other died of lung cancer at the 46th month on HTPN. The third patient, followed for 33 months, had transient severe liver function abnormalities associated with a blood transfusion. In groups 2 and 3, only one patient (with a history of probable liver disease before HTPN) developed biopsy-proven cirrhosis at the 60th month of HTPN. All four patients with clinically apparent liver disease developed persistent elevation of serum aspartate aminotransferase (AST) early in HTPN. Four other patients (all in group 3) with abnormal AST values in the early phase of HTPN normalized them later; they did not develop clinical liver disease over a mean follow-up time of 110 months (range, 39-152). None of the remaining eight patients (seven in group 2 and one in group 3) had significant liver function test abnormalities and none developed clinical liver disease over a mean follow-up period of 72 months (range, 39-120).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver dysfunction associated with long-term total parenteral nutrition in patients with massive bowel resection. 190 76

The preliminary results of a trial to examine and compare the safety, tolerability and efficacy of a single dose of teicoplanin with three doses of cephradine combined with metronidazole are presented in a series of 113 patients undergoing elective vascular surgery. There were no obvious differences in the infection rates and sepsis indicators in either group. Neither drug regimen produced any evidence of renal or hepatic damage, though the levels of three hepatocellular enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl-transferase (GGT), were seen to be transiently elevated, peaking 7 days post-operatively. The trial continues.
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PMID:A comparison of teicoplanin vs. cephradine and metronidazole in surgical prophylaxis: an interim analysis. 198 76

Scarcity of small donors results in a high mortality rate for children on liver transplant waiting lists. To alleviate this problem, we have recently started to reduce the size of livers from older donors to use in children. In the last year, a total of 20 liver transplants were performed in 17 patients, including seven reduced-size liver transplants (RSLT) in six children. Mortality on the waiting list has been reduced to negligible amounts compared with a mortality rate of 25% before starting RSLT in patients with acute liver failure or those whose weight was less than 10 kg. Children undergoing RSLT weighed 10.8 +/- 8.5 kg compared with 20.9 +/- 20.3 for all others (NS). Cold ischemia time was significantly longer in the RSLT group (9.5 +/- 3.0 v 6.0 +/- 2.8 hours, P less than .05) as was intraoperative blood loss (9.4 +/- 9.4 v 3.0 +/- 3.5 blood volumes). There was no significant difference in postoperative aspartate aminotransferase and prothrombin time between the two groups. Four children received a RSLT as a primary procedure and three have survived with good liver function. Two patients were retransplanted with RSLT after a failed first transplant and both died of nonhepatic complications. This compares with 11 of 13 survivors in the whole liver transplant group. Causes of death in children who died after RSLT include cytomegalovirus sepsis (2) and myocardial infarction(1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early experience with reduced-size liver transplants. 227 30

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


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