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

Cefotaxime is the most commonly used antibiotic for initial therapy of spontaneous bacterial peritonitis in cirrhosis. However, since the introduction of cefotaxime no study has been performed to investigate factors influencing prognosis in cirrhotic patients with this type of infection. In this study, predictive factors for infection resolution and patient survival were investigated in 213 consecutive episodes of spontaneous bacterial peritonitis in 185 cirrhotic patients. All patients were initially treated with cefotaxime. One hundred sixty-five episodes (77%) resolved with cefotaxime alone, and two more episodes (1%), initially unresponsive to cefotaxime, were cured after modification of antibiotic therapy. In a multivariate analysis (stepwise logistic regression), only 4 of 51 clinical and laboratory variables obtained at the time of diagnosis of infection were identified as independent predictors of infection resolution: band neutrophils in white blood cell count, community-acquired vs. hospital-acquired peritonitis, blood urea nitrogen level and serum aspartate aminotransferase level. No patient experienced serious adverse effects related to cefotaxime. Eighty-two patients died during hospitalization (38% mortality rate in relation to the 213 episodes of peritonitis). In the multivariate analysis, six variables were independently correlated with survival: blood urea nitrogen level, serum aspartate aminotransferase level, community-acquired vs. hospital-acquired peritonitis, age, Child-Pugh score and ileus. No microbiological data had predictive value for infection resolution or survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spontaneous bacterial peritonitis in cirrhosis: predictive factors of infection resolution and survival in patients treated with cefotaxime. 842 22

E7070 is a novel sulfonamide anticancer agent that disrupts the G1/S phase of the cell cycle. The objectives of this phase I study of E7070 were to estimate the maximal tolerated dose (MTD), to determine the recommended dose for phase II, and to clarify the pharmacokinetic profile of E7070 and its relation to polymorphisms of CYP2C9 (*2, *3) and CYP2C19 (*2, *3) in Japanese patients. Patients received 1-2-h i.v. infusions of E7070 (400, 600, 700, 800 or 900 mg/m2) on day 1 of a 21-day cycle. Twenty-one patients received between one and eight cycles of E7070. The dose-limiting toxicities (DLT) comprised leukopenia, neutropenia, thrombocytopenia, elevation of aspartate aminotransferase, colitis, and ileus. The mean area under the plasma concentration-time curve (AUC) for successive dose levels increased in a non-dose-proportional manner. Two patients were heterozygous for the CYP2C9 mutation. For CYP2C19, eight patients were wild type and the remainder had heterozygous (n = 8) or homozygous mutations (n = 5). Regarding the CYP2C19 genotype, the AUC of patients with mutant alleles were higher than those of patients with wild type at a dose of 600 mg/m2 or more. The severity of toxic effects, such as myelosuppression, seemed to depend on the AUC. No partial responses were observed. One patient treated at a dose of 700 mg/m2 experienced a maximum tumor volume reduction of 22.5%. The MTD was estimated to be 900 mg/m2. A dose of 800 mg/m2 is recommended for further phase II studies. The pharmacokinetic/pharmacodynamic properties of E7070 seemed to be influenced by CYP2C19 genotype. The observed safety profile and preliminary evidence of antitumor activity warrant further investigation of this drug in monotherapy or in combination chemotherapy.
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PMID:Phase I pharmacokinetic and pharmacogenomic study of E7070 administered once every 21 days. 1623 5

To overcome the barrier of size match, right lobe graft has been widely used in living donor liver transplantation (LDLT). We assessed donor outcome, with a focus on remnant liver volume (RLV) after right hepatectomy based on the experiences of 2 LDLT centers, as a means of guiding the establishment of safe RLV limits for donor right hepatectomy. Between January 2002 and December 2003, a consecutive 146 liver donors who underwent right hepatectomy with at least 12 months of follow-up were enrolled in this study. Donors were grouped into 2 groups according to RLV: group 1 (n = 74), <35% (range, 26.9-34.9) and group 2 (n = 72), > or = 35% (35.0-46.8). No donors died or suffered a life-threatening complication. Mean peak serum postoperative aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (IU/L) levels were 219.5 +/- 79.9 and 231.5 +/- 83.3 in group 1 and 210.3 +/- 81.6 and 225.8 +/- 93.0 in group 2 (P = 0.497 and 0.699), respectively. Mean peak serum total bilirubin (TB) (mg/dL) level in group 1 (3.4 +/- 1.6) was higher than in group 2 (2.8 +/- 1.4; P = 0.023). Overall 23 (15.8%) major morbidities, 10 in group 1 (13.5%) and 13 in group 2 (18.1%), occurred according to Clavien's system (P = 0.939). These included bleeding (n = 3 in group 1 and n = 6 in group 2; P = 0.282), ileus (n = 3 and 1; P = 0.324), biliary leakage (n = 4 and 4; P = 0.968), and pneumonia (n = 0 and 2; P = 0.149). Minor morbidities were also comparable in the 2 groups. In conclusion, the outcome of donors with an RLV of <35% was not different from that of donors with an RLV of > or = 35%, with the exception of transient cholestasis. Therefore, a remnant RLV of <35% does not appear to be a contraindication for right liver procurement in living donors.
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PMID:Outcome of donors with a remnant liver volume of less than 35% after right hepatectomy. 1644 1

Steatotic liver graft transplantation affect donor safety as well as recipient survival. We investigated safety of donors according to the extent of fatty change. We retrospectively reviewed donors who underwent right hepatectomy from September 1999 to April 2005, dividing them into three groups according to degree of macrovesicular fatty change upon intraoperative liver biopsy. Group 1 included patients with macrovesicular steatosis of 0 approximately 9%: group 2, 10 approximately 19% and group 3, at least 20%. Two hundred forty-five donors were enrolled with a male to female ratio of 2.02:1 and mean age of 31.8 years. There were 163 donors in group 1, 75 in group 2, and seven in group 3. There was no statistically significant difference in body mass index, operative time, blood loss, postoperative peak serum bilirubin, and aspartate transaminase levels among groups 1, 2, and 3. Overall complication rate, including reoperation, biliary stricture, wound infection, ileus, transfusion, bile leak and fluid collection were not different between the groups. Postoperative hospital stay was also not different. Peak alanine transaminase level was different between each group, and prothrombin time between group 1 and 3, but days until return to normal levels in all measured laboratory parameters were not different. Residual liver volume percent was significantly smaller among group 1 compared to others. In conclusion, fatty livers with less than 30% macrovesicular steatosis may be good donor candidates without significant complications as long as sufficient residual liver volume is left for the donor.
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PMID:Safety of donors with fatty liver in liver transplantation. 1698 14

This paper describes three cases of liver lobe torsion in rabbits presenting with anorexia, lethargy, jaundice and abdominal pain. This condition was associated with anaemia and elevation of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase. Abnormal radiological findings included hepatomegaly, gas-filled intestinal loops consistent with gastrointestinal ileus and ascites. Ultrasonographic findings included heterogeneous liver parenchyma, free abdominal fluid and reduced bowel motility. Diagnosis was confirmed by histopathological examination of the liver in all three cases.
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PMID:Liver lobe torsion in three adult rabbits. 1979 19