Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence suggests that interferon-alpha (IFN-alpha) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-alpha in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-alpha (5 x 10(6) IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-alpha has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.
 ...
PMID:Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-alpha in patients with advanced pancreatic cancer. Eastern Cooperative Oncology Group Protocol 3292. 893 68

Pruritus is a common symptom of chronic cholestatic liver diseases but is considered rare in chronic hepatitis. We observed pruritus to be an unusually common complaint in patients with advanced chronic hepatitis C. We reviewed the records of 175 chronic hepatitis C patients to identify patients with severe, diffuse, unexplained pruritus; 12 consecutive prospective patients undergoing liver biopsy for chronic hepatitis C served as controls. Assessment included laboratory biochemical tests and assessment of liver pathology by stage, grade, hepatic activity index, and a bile duct score. Pruritus was present in nine (5.1%) patients. Serum AST, ALT, alkaline phosphatase, GGTP, total bilirubin, and ferritin were similar in pruritics and controls. Pruritics had higher serum bile acids (2028.4 +/- 223.1 mmol/liter vs 423.1 +/- 194.3, P < 0.001), higher transferrin saturation (57.5 +/- 6.8% vs 33.2 +/- 3.3, P < 0.01), and lower HCV RNA by bDNA (24.5 +/- 12.7 x 10(5) vs 172.7 +/- 54.1 x 10(5), P < 0.05). Pathology revealed cirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P < 0.01). Pruritics had higher pathologic stage (3.7 +/- 0.2 vs 2.2 +/- 0.4, P < 0.01), grade (4.4 +/- 0.2 vs 2.1 +/- 0.2, P < 0.001), activity index (14.3 +/- 1.9 vs 8.6 +/- 1.9, P < 0.025), and bile duct score (7.6 +/- 0.6 vs 4.7 +/- 0.4, P < 0.01). Of eight pruritics treated with IFN-alpha2b, two had complete ALT response and one relapsed. Pruritus followed a relapsing course and only three patients partially responded despite a variety of interventions. In conclusion, pruritus is a common complication of advanced CHC. Its presence is associated with high serum bile acids, advanced pathology and bile duct abnormalities. The clinical course of pruritus is relapsing and response to therapy is inconsistent. These features suggest that pruritus in CHC has a pathogenesis that may vary from that of chronic cholestatic diseases.
 ...
PMID:Pruritus in chronic hepatitis C: association with high serum bile acids, advanced pathology, and bile duct abnormalities. 914 69

One hundred patients with severe Chronic C Hepatitis, > 60 years of age and a life expectancy > 10 yrs were randomised to receive a course of lymphoblastoid a-IFN or a non specific support therapy as control. Patients randomised to IFN (no. 50) were treated with 3MU i.m. every two days for 2 months and then with 6MU i.m. every second two days for additional 10 months. All patients were followed-up for 12 months at the end of treatment. At the end of treatment, 30/50 patients in the IFN group showed a complete remission with normalisation of ALT and AST values (60%). Partial remission occurred in 11 patients (22%) whose transaminase values improved but did not normalise. No response was seen in 9 cases (18%) who showed similar pre- and post- treatment transaminase levels. On the contrary, normalisation of ALT-AST was observed in just two patients assigned to the non-specific therapy, whereas pre- and post-treatment values were similar in the remaining 48 patients. In patients receiving IFN a marked histological improvement was observed at the end of therapy in 22 responders (73.3%) and in 6 partial or non responders (30%) treated with IFN. No histological improvement was observed in control patients. At the end of the 12-month follow-up (24 months from the beginning of the study), 12 responders relapsed (40%) showing levels of transaminase which returned to the pre-treatment values within the second month from the IFN discontinuation. Therefore 18 out of 50 patients (36%) showed a long-term response to lymphoblastoid interferon. Lymphoblastoid a-IFN is an effective and safe therapy in elderly patients whose life expectancy justify its use and generates responses which are similar to those observed in younger subjects.
 ...
PMID:Treatment of chronic hepatitis C with lymphoblastoid interferon alpha in elderly patients. 944 98

Hepatitis C virus (HCV) infection usually recurs after orthotopic liver transplantation (OLT), and most patients develop graft damage. This study compared the efficacy of interferon alfa (IFN-alpha) and ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft. Thirty OLT recipients with chronic hepatitis C were randomized to receive either IFN-alpha (3 MU three times a week) or ribavirin (up to 1.2 g daily) for 24 weeks. Virological, biochemical, and histological responses to treatment were assessed. Twenty-eight patients completed the treatment regimen, two ribavirin-treated patients being withdrawn because of severe hemolysis. Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin (93%) and 6 of 14 patients receiving IFN-alpha (43%; P=.01). Lobular inflammation was reduced in 9/14 ribavirin-treated (64%) and 3 of 14 IFN-alpha-treated patients (21%; P=.05), each of whom had a biochemical response. However, the total histological activity index did not improve in either the interferon (P=.43) or the ribavirin (P=.96) group. Posttreatment viremia levels were significantly reduced in IFN-alpha-treated (P=.05) but not in ribavirin-treated (P=.88) patients. Hemolysis occurred in all ribavirin-treated patients, with serum hemoglobin decreasing to < 10 g/dL in 50%. Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment (P=.02 and P=.004, respectively). We concluded that in patients with chronic hepatitis C after OLT, IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation, but not the total histological activity index. These findings provide a rationale for combination therapy in the post-OLT setting, although patients must be carefully monitored for hemolysis.
 ...
PMID:A randomized study comparing ribavirin and interferon alfa monotherapy for hepatitis C recurrence after liver transplantation. 958 98

Interferon alpha (IFN alpha) has been widely used as therapy for chronic hepatitis C. However, changes in glucose metabolism during IFN alpha therapy in patients with chronic hepatitis C remain unknown. To study the effects of IFN alpha on glucose tolerance in patients with chronic hepatitis C, we prospectively examined glucose tolerance in 15 patients with chronic hepatitis C before and four weeks after the start of IFN alpha therapy. Serum bilirubin, albumin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) improved after the therapy compared with before (p < 0.05, respectively), while levels of fasting blood sugar, blood sugar at 30 min in 75 g-oral glucose tolerance test (OGGT) and fasting immunoreactive insulin (IRI) decreased (p < 0.05, respectively); insulinogenic index (II) also increased (p < 0.05). Response patterns in 75 g OGGT before therapy were: four patients in normal pattern, five in a borderline pattern and four in a diabetic pattern, whereas those after therapy were changed to four in a normal pattern, and eight in a borderline pattern. Changes in AST between before and after therapy were correlated with those in blood glucose at 30 min in a 75 g-OGGT (r = +0.648, p = 0.042). Although interferons have been reported to impair glucose tolerance in viral infection, the results of the present study indicate that hepatic functional recovery may be associated with improved glucose tolerance in patients with chronic hepatitis C treated with IFN alpha.
 ...
PMID:Changes in glucose tolerance after interferon-alpha therapy in patients with chronic hepatitis C. 960 92

Thirty-five outpatients (7 F, 28 M, mean age 39.8 years) with histologically confirmed active chronic B hepatitis, have been immunised with specific anti-HBV vaccine (Engerix B 20 mcg, SmithKline Beecham Biologicals, Rioxensart, Belgium) on days 0, 30 and 60. Hepatitis B markers, HBV-DNA and anti-HDV antibodies were determined on the same day of vaccination. One week after the last dose of anti-HBV vaccine, 15 and 10 patients have been treated respectively with alpha-leukocyte-IFN and beta-natural-IFN at the dose of 6 mU three times/week for one year; the remaining 10 patients were included in the control group. Hepatitis B and D markers and transaminases were monitored monthly during IFN therapy. Within one month from the last dose of anti-HBV vaccine, 20 patients out 35 have shown a transitory disappearance of HBV-DNA. After the 2nd dose in 4 patients a marked increase in AST and ALT levels was observed (up to 10 times the normal values). After the 3rd dose (last dose) five HBV-DNA-negative patients have shown transitory low levels of anti-HBs antibodies; moreover, after the last dose of anti-HBV, one HBV-DNA-negative patient resulted HBV-DNA-positive. After one year of IFN-therapy, 8 patients out 15 treated with alpha-leukocyte-IFN and 2 treated with beta-natural-IFN, have shown normalisation of transaminases. These results confirm the effectiveness of an anti-HBV vaccination before an IFN treatment and a better response achieved with alpha-leukocyte-IFN.
 ...
PMID:Anti-HBV vaccination before therapy with interferon (IFN) in chronic B hepatitis. 971 55

Medical guidelines for interferon-alpha2a or -alpha2b (IFN-alpha) treatment of chronic hepatitis C virus (HCV) infection depend upon baseline liver histology. A better long-term response to IFN-alpha therapy correlates with less inflammation and absence of cirrhosis. It has been suggested that the presence of cirrhosis in patients with chronic hepatitis C virus infection may be predicted based on an AST/ALT ratio > or = 1. This study was designed to determine if the presence of cirrhosis can be predicted in patients with chronic HCV infection by such a ratio. Seventy-seven patients, including 23 cirrhotics, with chronic HCV infection were studied. Serum ALT, AST, and HCV-RNA levels and hepatic activity index (HAI), reflecting histologic inflammation in all liver biopsies, were assessed. AST/ALT ratios and mean ALT, AST, and HCV-RNA were determined for both cirrhotic and noncirrhotic patients. HAI was correlated with ALT, AST, and HCV-RNA levels, the latter determined by quantitative RT-PCR. The likelihood ratio (LR) and positive predictive value of an AST/ALT ratio > or = 1 for cirrhosis was 7.3 and only 77%, respectively. In cirrhotics vs noncirrhotics, there were no significant differences between mean serum ALT (149 +/- 28 vs 176 +/- 17 units/liter), AST (139 +/- 28 vs 102 +/- 8 units/liter), or HCV-RNA levels (589,160 +/- 147,053 vs 543,915 +/- 75,497 copies/ml), respectively. There was a significant, but clinically weak, correlation between serum ALT and HAI (r = 0.234), and none between HAI and either serum AST or HCV-RNA levels. Our results support the need for a liver biopsy prior to treatment of chronic HCV infection, since the AST/ALT ratio fails to predict accurately the presence of cirrhosis.
 ...
PMID:AST/ALT ratio > or = 1 is not diagnostic of cirrhosis in patients with chronic hepatitis C. 975 86

To evaluate the safety, toxicity, and maximum tolerated dose (MTD) of IFN beta-1a (Rebif, Serono Laboratories, Inc.) in patients with malignant diseases unresponsive to standard therapies and to assess the pharmacodynamics and pharmacokinetics associated with IFN beta-1a administration, an open-label, single-center phase I study was designed. Thirty-four patients were enrolled and treated with IFN beta-1a. All had measurable solid neoplasms or evaluable hematological malignancies. All patients received a single i.v. bolus dose of IFN-beta-1a on day 1, followed 7 days later by daily s.c. injections for 28 consecutive days. Successive groups of three patients received increasingly higher doses (in geometric progression from 1.5 million international units (MIU)/m2 to 24 MIU/m2) until dose-limiting toxicities were noted. Pharmacokinetic and biological studies, including measurement of the activity of 2',5'-oligoadenylate synthetase (2',5'-OAS) in peripheral blood mononuclear cells and serum levels of soluble Tac (CD 25) and beta-2 microglobulin, were performed on patients who agreed to participate. i.v. and s.c. doses of IFN beta-1a up to 24 MIU/m2 were administered. The most frequent adverse events (AEs) were constitutional symptoms. Grade III AEs during i.v. dosing included fever, elevation of bilirubin, and infection unrelated to therapy. No grade IV events were seen. AEs noted during continuous s.c. therapy included fever, liver transaminase increase, albuminuria, fatigue, nausea, myalgia, and rigors. Dose-limiting toxicities were encountered during s.c. dosing at the 24-MIU/m2 and 18-MIU/m2 dose levels and included gastrointestinal toxicity, elevations of aspartate aminotransferase and alanine aminotransferase, and albuminuria. The s.c. MTD was determined to be 12 MIU/m2, although there was great variability in the individual patient's ability to tolerate IFN beta-1a. 2',5'-OAS activity, thought to be indicative of IFN activity, increased within hours after i.v. and s.c. dosing, with the level remaining persistently elevated during the s.c. daily injections. The highest peak level was attained in the 6-MIU/m2 group. There was no evidence that the increase in 2',5'-OAS activity decayed with repetitive dosing, nor was there evidence of accumulation in this pharmacodynamic marker. Serum beta-2-microglobulin levels showed a modest time- and dose-dependent increase after s.c. administration of IFN beta-1a, with the largest increase seen at the 24-MIU/m2 dose level. There were no clear dose-dependent responses noted in soluble Tac serum levels. IFN beta-1a was well-tolerated when administered by a single i.v. bolus injection at doses up to and including 24 MIU/m2. Daily s.c. injections for at least 28 days were well-tolerated at doses up to and including 12 MIU/m2, with some patients tolerating doses twice as high as this. The MTD for the i.v. route could not be clearly determined according to the guidelines of the protocol. However, i.v. bolus doses up to 24 MIU/m2 were relatively well-tolerated. For the s.c. route, the MTD was determined to be 12 MIU/m2, but there was great interpatient variability, with some patients able to tolerate higher doses.
 ...
PMID:A phase I study of recombinant interferon-beta in patients with advanced malignant disease. 1063 30

To develop prognostic models for identifying children with hepatitis B who are likely to respond to interferon-alpha (IFN-alpha) or to spontaneously seroconvert, we evaluated results of a multinational controlled trial comprising 70 children with chronic hepatitis B who received IFN-alpha and 74 children who did not receive therapy. Prognostic models were developed using SMILES (similarity of least squares), which is a data analysis network that incorporates multidimensional relationships in the clinical data of complex diseases. Commonly collected clinical data included age, gender, serum aminotransferase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and hepatitis B virus (HBV) DNA levels, and IFN-alpha dose. Additional data included pretreatment directional information (e.g. increases or decreases in serum aminotransferase and HBV DNA levels), liver biopsy results, race and transmission mode. Using data available prior to initiation of treatment, the SMILES models achieved prospective predictions of 89% for responders, 96% for non-responders, 100% for seroconverters and 93% for non-seroconverters. Although not predictive by themselves, the variables that had the greatest impact on predictions for IFN-alpha response were HBV DNA pretreatment direction, baseline HBV DNA, IFN-alpha dose and gender. The variables that had the greatest impact on predictions for spontaneous seroconversion were ALT pretreatment direction, baseline HBV DNA level, age and AST pretreatment direction. Therefore, these models may be useful in determining, in children with hepatitis B, the likelihood of response to IFN-alpha and spontaneous seroconversion.
 ...
PMID:Statistical models for predicting response to interferon-alpha and spontaneous seroconversion in children with chronic hepatitis B. 1076 45

Traditional Chinese medicine is still being extensively used for treatment of liver disease in China. The anti-viral herbs, Phyllanthus amarus, P. niruri and P urninaria, and Oxymatrine extracted from Sophora flavecientis and S. subprostratae, have been shown to have a remarkable HBV suppressing effect with a serum conversion rate for HBeAg and HBV DNA around 45%, similar to that of IFN-alpha. The anti-inflammatory compound, Stronger NeoMinophagen C (SNMC), is a Japanese preparation of glycerrhizin, extracted from Glyceriza glabra, which has shown an effective rate of ALT and AST normalization and reduction to < 60 U/L in 65.6%, and 73.5% of patients. Compound 861, made of 10 herbs with Salvia miltiorrhiza as its chief component, has been shown experimentally to be effective in suppressing fibrogenesis, enhancing collagen degradation, and inhibiting TIMP expression. Clinically, an open trial of 2,000 patients showed improvement of symptoms in 83% and normalization of serum ALT in 82%. In a controlled study of 107 patients with HBV-related diseases, double liver biopsies showed that the fibrosis reversal rate after 6 months treatment with Cpd 861 was 78% in S2, 82% in S3 (precirrhotic stage) and 75% in S4 (early cirrhosis), as assessed by Scheuer's and Chevallier's criterion. In conclusion, traditional Chinese medicine has great potential in the treatment of chronic hepatitis B.
 ...
PMID:Treatment of chronic liver diseases with traditional Chinese medicine. 1092 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>