gamma-Hydroxybutyric acid (GHB) is currently used to induce and maintain abstinence from alcohol. Cases of craving and desire to increase doses of GHB have been reported in both clinical trials and ...nonclinical self-administration. The enhancement of dopamine activity induced by GHB receptor activation might play a role in the euphoric effect and potential craving and the consequent abuse of this drug. Naltrexone (NTX), a mu-opioid antagonist, is effective in inducing and maintaining abstinence from alcohol, reducing relapses in heavy drinking and craving for alcohol in alcohol-dependent outpatients. Taking into account the alcohol antireward property of NTX, we tested its activity in reducing craving for GHB in 3 consecutive cases of alcoholics who manifested craving for this drug. In all patients the combination with NTX suppressed the craving for GHB. The antireward effect of NTX likely results from its interference with the GHB-induced dopamine release, leading to a partial blockade of the GHB reinforcing effect responsible of the craving for the drug. A combined therapy with GHB and NTX seems to be able to suppress craving for the former, thus improving the manageability and safety of treatment.
Hepatocytes isolated from 101 biopsies were examined for membrane-bound IgG. The sera of the patients were tested for anti-liver-specific lipoprotein by radioimmunoassay and for liver membrane ...autoantibody (by indirect immunofluorescence on isolated rabbit hepatocytes. The seven patients with normal liver or minor nonspecific alterations were negative for membrane IgG and serum antibodies. Membrane IgG with granular distribution was found in 41 patients 21 hepatitis B virus-related chronic active hepatitis (CAH), 3 cryptogenic CAH, 3 chronic persistent hepatitis, 6 prolonged viral hepatitis, 1 alcoholic cirrhosis, and 6 primary biliary cirrhosis. Membrane IgG with linear fluorescence pattern was detected in 12 cases (4 autoimmune CAH, 3 HBsAg-positive CAH, 2 alcoholic cirrhosis, 1 anti-HBc positive CAH, 1 cryptogenic CAH, and 1 prolonged viral hepatitis). A strong association between granular IgG and serum HBsAg was found. Nuclear localization of IgG was found in 34 patients and correlated with the positivity of granular membrane IgG. The highest prevalence of anti-liver-specific lipoprotein was found in primary biliary cirrhosis and autoimmune CAH cases which were also positive for liver membrane autoantibody. No relationship was found between the presence of membrane IgG and circulating liver-specific autoantibodies. Membrane IgG and anti-liver-specific lipoprotein correlated with the presence of moderate and severe portal inflammatory infiltration but not with piecemeal necrosis or transaminase levels. Eleven of the twelve patients with linear membrane IgG presented chronic active liver disease with moderate to severe signs of liver damage. Therefore, it is suggested that, while granular membrane IgGs are related to hepatitis B virus, antigenic expression on the hepatocyte surface and/or the presence of immune complexes, linear membrane IgG could play a role in the immunopathogenesis of liver cell damage particularly in "autoimmune" cases which present high percentages of positive cells liver-specific autoantibodies.
The silicon pixel detector (SPD) comprises the two innermost layers of the ALICE Inner Tracking System (ITS). It is instrumented with arrays of hybrid pixels made out of 150
μm thick ASICs, each ...containing 8192 readout cells, bump bonded to 200
μm thick silicon sensors. The dimensions of the pixel cells are 50
μm (
rϕ)×425
μm (
z). Prototype assemblies have been tested in high-energy particle beams at the CERN SPS. The results of measurements in a multi-track environment, from interactions of an In beam at 158
AGeV on a Pb target, are reported.
Defects in T lymphocyte subpopulations and in the functional characteristics of such cells have been thought to play a role in the evolution of chronic hepatitis B, but the precise nature of the ...alterations and their significance remains unresolved. We studied lymphocyte subsets in 27 patients with chronic hepatitis B utilizing standard monoclonal antibodies including Leu 1,2a,3a,7 and D1/12 (against the common determinant of the Dr molecule), as well as a newly described monoclonal antibody, "5/9," which is thought to characterize a unique subpopulation of T4 cells with specific helper/inducer function. These results were compared with those obtained using the autologous mixed lymphocyte reaction assay for the same patients in order to further delineate the lymphocyte alterations in chronic hepatitis B. A significant reduction in the mean number of Leu 3a (T4) positive cells was observed as well as a reduction in the number of 5/9 positive cells. These changes were most evident in those positive for HBeAg in serum. Reduction in Leu 3a cells was associated with a reduced autologous mixed lymphocyte reaction assay response, and was most marked in the HBeAg-positive individuals. These findings suggest that HBeAg-positive patients in whom active viral replication is occurring have a defect in T lymphocyte number and function, which may be due in part to reduced 5/9 positive cells. These alterations may be related to the persistence of virus in chronic active hepatitis B patients.
Backgrounds/Aims: Knowledge of the proportion of liver cirrhosis attributable to the main risk factors is largely based on methodologically questionable clinical reports.
Methods: The proportion of ...newly diagnosed cases of symptomatic liver cirrhosis attributable to known risk factors was estimated by a case-control study performed during 1989–1996 in 23 medical divisions of several hospitals distributed throughout Italy. Cases were 462 inpatients with cirrhosis admitted for the first time for liver decompensation. Controls were 651 patients admitted during the same period and to the same hospitals as the cases, for acute diseases unrelated to alcohol and virus infection. The proportion of symptomatic liver cirrhosis cases due to alcohol intake and hepatitis B and C viruses and the combination of these was expressed as the population attributable risk.
Results: Attributable risks were 67.9% (95% confidence interval (CI): 53.8–79.4) for alcohol, 40.1% (95% CIL 35.3–45.2) for hepatitis C virus and 4.4% (95% CI: 2.5–7.6) for hepatitis B virus. The three factors together explained 98.1% (95% CI: 81.6–99.6) of cases in men and 67.0% (95% CI: 50.4–85.8) in women.
Conclusions: Alcohol is the risk factor with the highest impact on symptomatic liver cirrhosis risk in Italy. From a public health viewpoint, with the elimination of the well-known risk factors (particularly alcohol and hepatitis C virus), liver cirrhrosis should become a rare disease.
Several experimental studies have suggested that specific nutrients might play a role on the risk of liver damage. Nevertheless, few epidemiological studies have evaluated the role of diet on the ...risk of symptomatic liver cirrhosis, giving contradictory results. To evaluate the role of the intake of nutritional factors and dietary patterns on the risk of symptomatic liver cirrhosis and to examine their combined action with alcohol consumption we used data from the Italian Study on Liver Cirrhosis Determinants project. From 1994 to 1998 all the consecutive cirrhotic inpatients admitted to 19 Italian collaborative hospitals for signs of liver decompensation in whom the diagnosis of liver cirrhosis was made for the first time (259 cases) and one or two gender, age and area of residence matched individuals (416 controls) were recruited. Data on lifetime alcohol intake, usual consumption of 191 food items and on markers of hepatitis B and C viral infection were collected. The analysis of principal components identified a nutritional pattern positively correlated with vegetable and fruit intakes and negatively with animal and no-fruit sugar products. With respect to abstainers, relative risks in consumers of use ≤25 and ≥51 g/day of alcohol increased from 0.4 95% confidence interval 0.0, 5.9 to 9.3 1.3, 69.0 and from 2.1 1.1, 4.2 to 18.1 2.8, 118.3 for the lowest and the highest value of this nutritional pattern, respectively. Diet might therefore modulate the damaging effect of alcohol on the liver.
Venom immunotherapy (IT) is a very effective method for the treatment of Hymenoptera venom allergy. We compared safety, efficacy, and modulation of specific immunologic parameters in 70 patients ...sensitized to Apis mellifera, treated for > or = 5 years with standardized quality (SQ) aqueous IT, either with a rush (n = 20) or with a cluster (n = 20) induction protocol, or with an SQ depot extract and a cluster induction protocol (n = 30). We made an open, noncontrolled study. Side effects were monitored and the effects of field stings during the maintenance phase of the treatment and after its interruption were recorded. Skin reactivity to Apis was measured by end point dilution and specific serum immunoglobulin E (IgE) were measured by a solid-phase-based assay. The depot IT was better tolerated than aqueous IT with rush induction. This was caused by mainly the lower frequency in the induction phase of systemic side effects (3.4% versus 36.8% p < 0.0041 on a "per patient" and 0.1% versus 0.9% p = 0.0092 on a "per dose "basis, respectively). The cluster protocol with the aqueous extract tended to be better tolerated that the rush protocol. About one-half of patients from each group were re-stung during the study and all suffered only minor discomfort. Reduction of skin reactivity and of serum-specific IgE was significant in the three groups (p < 0.02 in all cases). SQ Depot IT to Apis venom allergy administered with a cluster protocol induces less side effects and is equally effective then IT with SQ aqueous extract administered with a rush protocol.
PDF
