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Biomedical subjects

A Picciotto

Publications and source records attributed to A Picciotto.

At least 91 records · Page 5Linked to original sources
PubMed1977

Toxic and immunodepressive effects of L-asparaginase from E. coli and from Erwinia carotovora following chronic administration in rats.

The effects of the administration of L-asparaginase from E. coli and Erwinia carotovora were studied in rats treated for 90 days with 800 or 3200 IU/kg body weight. The studies included overall toxicity on the liver, pancreas, and enteric mucosa as evaluated by both opitcal and electron microscopic examination, biochemical findings, behaviour of IgM-hemolysin producing cells, and antias-paraginase antibody production. The toxic effect and the immunodepressive activity appeared rather early, tending later to decrease. No sex correlation or clear cut dose correlation were observed. However, slight differences in toxicity between the two types of L-ASN-ase were present.

Animals↗
PubMedDate not supplied

HLA-DR antigens in HBsAg-positive chronic active liver disease with and without associated delta infection.

The A, B, C and DR locus specificities of the human leukocyte antigens system (HLA) were determined in 45 delta-positive and 44 delta-negative Italian patients, all with HBsAg-positive chronic active liver disease; controls were 526 healthy Italian blood donors matched for age, sex and geographical origin. HLA-A, B, C gene frequencies were not significantly changed. In delta-positive patients, the frequencies of the DR locus specificities were: DR2, 37.8%; DR3, 20%; DR4, 11.1%. In the delta-negative patients, the frequencies were: DR2, 13.6%; DR3, 36.4%; DR4, 0%. Control frequencies were: DR2, 19.4%; DR3, 17.1%; DR4, 18.5%. The corrected p values of the differences between controls and delta-positive patients were: DR2, pc = 0.046; DR3, pc = NS (not significant); DR4, pc = NS. The corrected p values of the differences between controls and delta-negative patients were: DR2, pc = NS; DR3, pc = 0.03; DR4, pc = 0.002. These findings show that: (a) DR3, a genetic marker of autoimmunity, might assist the establishment of chronic HBsAg liver disease in the absence of delta superinfection; (b) DR2 is linked with failure to clear the delta agent, and (c) DR4 may protect from virus B persistence. Identification of adventitious factors such as delta may help uncover a subgroup of HBsAg carriers who are genetically predisposed to develop chronic liver disease.

Adolescent↗
PubMedDate not supplied

Mutations of the HFE gene and the risk of hepatocellular carcinoma.

The discovery of the C282Y and H63D point mutations in the hereditary hemochromatosis-associated HFE gene allows us to study the molecular basis of congenital and acquired iron overload disorders. In hereditary hemochromatosis an increased frequency of the C282Y and, to a lesser extent, of the H63D mutations has been established, but their role in other conditions associated with iron overload and their prevalence in the normal population are still under investigation. We sought to determine the presence of such mutations, and their possible involvement in the multi-step neoplastic transformation of the hepatocytes, in patients diagnosed with hepatocellular carcinoma, a frequent complication of iron-induced liver cirrhosis occurring in untreated hereditary hemochromatosis subjects. The frequency of the C282Y and H63D mutations was determined in DNA from 12 patients with hepatocellular carcinoma and with no clinical signs of hereditary hemochromatosis. The frequency of the mutations was also determined in 130 normal subjects. A germline C282Y mutation was found in none of the hepatocellular carcinoma patients; the frequency of the H63D mutation was not increased, compared to the 130 controls. The allele frequencies of the C282Y and H63D mutations in the normal population were 0.042 and 0.185, respectively. In conclusion, we suggest that the hereditary hemochromatosis-related mutations of the HFE gene do not play a significant role in the pathogenesis of hepatocellular carcinoma.

Aged↗
PubMedDate not supplied

Antiviral activity of amantadine in elderly patients with chronic hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) infection is a worldwide problem of public health. Epidemiological studies have shown a significant higher prevalence of infection in the elderly. Amantadine is an antiviral agent active against the influenza A virus that has been used in cases of chronic hepatitis C. OBJECTIVES: To evaluate the antiviral activity and the safety of amantadine (200 mg daily for 6 months) in elderly patients with chronic hepatitis C. METHODS: The study group consisted of 23 consecutive patients over 65 years suffering from chronic hepatitis C. Aminotransferase (ALT) levels were tested at baseline, at 15 days and then monthly until the end of therapy. HCV genotype was determined at baseline. A quantitative HCV-RNA measurement was performed at baseline, at 15 days and at the 1st, 3rd and 6th month of treatment. RESULTS: 13 males and 10 females were enrolled (mean age 70.1 +/- 3.4 years; range: 65-75). The mean ALT levels did not change significantly during therapy except in 1 patient subsequently returned normal. The HCV-RNA remained detectable in all patients, but a significant difference in response was observed in patients infected by genotype 1b. CONCLUSIONS: Our results confirm the antiviral activity of amantadine against HCV, mainly for genotype 1b with initial high viral load. No consistent effects on aminotransferases were observed.

Administration, Oral↗
PubMedDate not supplied

Modifications in the serum concentrations of prolyl hydroxylase in patients with chronic hepatitis B during and after interferon therapy.

A total of eight patients with chronic active HBsAg-positive hepatitis was treated with recombinant interferon-alpha 2b for 12 months and serum aspartate aminotransferase, alanine aminotransferase, gamma-globulin and prolyl hydroxylase concentrations were determined every 3 months. Liver biopsies after 12 months' treatment revealed a significant (P less than 0.05) reduction in the histological activity score. After 6 months, alanine aminotransferase (P less than 0.01) and aspartate aminotransferase (P less than 0.05) concentrations fell significantly compared with baseline concentrations. Serum prolyl hydroxylase concentrations declined significantly (P less than 0.05) after 15 months and remained depressed. It is concluded that interferon-alpha 2b therapy reduced fibrogenetic activity in chronic active hepatitis B.

Adult↗
PubMedDate not supplied

Probability of non-response during interferon therapy in patients with chronic hepatitis C.

BACKGROUND/AIMS: About 50% of patients with chronic hepatitis C do not respond to interferon therapy and this failure is expensive. The aim of this study was to identify possible predictive factors of biochemical non-response during interferon therapy among biochemical, virological (HCV genotype), histological (Knodell's score) and pharmacokinetic (monoethylglycinexylidide formation test) pre-treatment parameters. METHODOLOGY: Our study included 60 patients with chronic hepatitis C undergoing a course of Interferon therapy. Patients whose serum ALT levels were normal at the 3rd month of therapy and remained so until the end of treatment were regarded as responders. RESULTS: In univariate analysis, only the gamma-glutamyltransferase (gamma-GT) and the gamma-GT/alanine aminotranferase ratio were significantly higher in non-responder patients. Multivariate logistic analysis showed that high gamma-GT levels, high histological activity index, low monoethylglycinexylidide formation rate and viral genotype 1 were the best combination for the identification of non-responder patients (16.7% error rate). By adding alanine aminotranferase modification at the 1st month of therapy the probability error was reduced to 5%. CONCLUSIONS: These results show that the combination of biochemical, histological, virological and pharmacokinetic pre-treatment variables, associated with alanine aminotranferase modification at the 1st month of therapy, can predict non-response to interferon and allow therapeutic modifications.

Adult↗
PubMedDate not supplied

Hepatitis G virus infection in intravenous drug users with or without human immunodeficiency virus infection.

BACKGROUND/AIMS: To evaluate the HGV infection prevalence in a group of intravenous drug users with or without human immunodeficiency virus coinfection. METHODOLOGY: We studied 57 patients (48 males and 9 females) who were either previous or still ongoing intravenous drug users. Thirty-seven patients were HIV+ve, 55 patients were anti-HCV+ve and 3 patients were HBsAg chronic carriers. Patient sera were tested for HGV-RNA, anti-E2, qualitative and quantitative HCV-RNA as well as for HCV genotypes. Moreover, the ALT level was checked in the serum sample of each patient. RESULTS: We found a high prevalence (35/57; 61.4%) of HGV infection in our patients. HGV-RNA was detected in 16 out of the 57 intravenous drug users (28%). In particular HGV-RNA was positive in 12 out of the 37 HIV+ve patients (32.4%) and in 4 out of the 20 HIV-ve patients (20%). Anti-E2 were detected in 19 out of the 57 patients (33.3%) with greater prevalence among HIV-ve subjects (12/20; 60%) compared to HIV+ve group (7/37; 18.9%). This resulting difference was statistically significant (P < 0.05). All HGV-RNA+ve/anti-E2+ve patients were anti-HCV/HCV-RNA+ve and none of our patients were anti-E2+ve/HGV-RNA+ve at the same time. Significant differences were not found between HGV-RNA+ve and HGV-RNA-ve patients as far as clinical and virological data are concerned. CONCLUSIONS: The prevalence of HGV infection in intravenous drug users proved to be high especially in the HIV+ve group. Moreover HGV was associated with HCV in all our cases. The actual clinical impact of HGV infection remains unclear since HGV does not seems to influence the biochemical, virological or histological alterations caused by HCV infection.

Adult↗
PubMedDate not supplied

A new assay for hepatitis C virus (HCV) core antigen detection: an alternative to nucleic acid technologies in positive or indeterminate anti-HCV subjects?

Markers of viral replication are fundamental tools for understanding the mode of transmission, diagnosis and management of hepatitis C virus (HCV) infection. A new enzyme-linked immunosorbent assay for quantitative detection of free and complexed HCV core antigen (HCV Ag) has been developed. The aim of this study is to evaluate the clinical performance of the new test and compare it with the most widely used commercially available RT-PCR-based assay. To determine the cut-off value we tested 60 samples from anti-HCV negative samples and selected a qualitative cut-off value of 3 pg/ml. To evaluate the usefulness of the new assay in confirming serologically indeterminate results we collected 62 sera. To evaluate the HCV Ag and HCV-RNA relationship we tested 245 samples from patients with different clinical conditions. The results of 61 out of 62 (98.4%) anti-HCV indeterminate samples were found to agree, whereas only one serum was found to be RT-PCR positive and HCV Ag negative. We also found the results to agree in 77.6% (190/245) of the samples from infected patients, while we observed higher agreement in untreated patients, both with and without evidence of liver damage. The correlation coefficient (r) observed between HCV Ag and HCV-RNA was 0.88. The regression line meets the cut-off value at an HCV-RNA concentration of approximately 40,000 IU/ml. In conclusion, we found that the results from the total HCV Ag test agree with the RT-PCR results and therefore we believe that this test could become a useful tool for the diagnosis and management of HCV infection.

Hepatitis C Antigens↗