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Biomedical subjects

L Pagliaro

Publications and source records attributed to L Pagliaro.

At least 91 records · Page 5Linked to original sources
PubMed1992

Distal spleno-renal shunt versus endoscopic sclerotherapy in the prevention of variceal rebleeding. A meta-analysis of 4 randomized clinical trials.

Meta-analysis was used to evaluate 4 clinical trials comparing distal spleno-renal shunt (DSRS) with endoscopic sclerotherapy (EVS) in the prevention of variceal rebleeding: the interval between bleeding and therapy ranges from < 14 days to > 100 days. A questionnaire was sent to each author of the published trials concerning methods, definitions and results of the trials in order to obtain more detailed and up-to-date information. The selected end-points for the meta-analysis were: rebleeding, mortality and chronic encephalopathy. Analysis of the results in the questionnaires was made using the method proposed by Collins. The pooled relative risk (i.e. the combined Odds ratio of each trial as an estimate of overall efficacy) of rebleeding was statistically reduced by DSRS (0.16; 95% confidence interval 0.10-0.27). Despite this, the overall risk of death following DSRS was only marginally decreased (0.78; 95% confidence interval 0.47-1.29); the lack of homogeneity in the results does not permit any significant conclusions on this end-point. However, in non-alcoholic patients, the decrease in risk of death was greater, and this without heterogeneity, following DSRS than EVS (0.59; 95% confidence interval 0.23-1.50). The overall risk of chronic encephalopathy was slightly increased after DSRS (1.86; 95% confidence interval 0.90-3.86). In conclusion, DSRS significantly reduced the risk of rebleeding compared to EVS without increasing the risk of chronic hepatic encephalopathy. However, DSRS did not significantly affect the overall death risk. Only in non-alcoholic disease did it seem to show an advantage over EVS.

Brain Diseases↗
PubMed1992

2-Deoxyglucose and cytochalasin D modulate aldolase mobility in living 3T3 cells.

Approximately 23% of the glycolytic enzyme aldolase in the perinuclear region of Swiss 3T3 cells is immobile as measured by FRAP. Previous studies suggest that the immobile fraction may be associated with the actin cytoskeleton (Pagliaro, L. and D. L. Taylor. 1988. J. Cell Biol. 107:981-991), and it has been proposed that the association of some glycolytic enzymes with the cytoskeleton could have functional significance, perhaps involving a fundamental relationship between glycolysis, cytoplasmic organization, and cell motility. We have tested the effect of a key glycolytic inhibitor and an actin cytoskeletal modulator on the mobility of aldolase in living cells directly, using fluorescent analog cytochemistry and FRAP. We report here that the competitive hexokinase inhibitor 2-deoxyglucose releases the bound fraction of aldolase in 3T3 cells within 10 min, and that this process is reversible upon washout of the inhibitor. A similar result is produced with the actin-binding agent, cytochalasin D. These results are consistent with models in which glycolytic enzymes are not exclusively diffusion-limited, soluble proteins, but may exist partially in the solid phase of cytoplasm. Such organization has significant implications for both the modulation of cytoplasmic structure and for cellular metabolism.

3T3 Cells↗
PubMed1992

Prevention of upper gastrointestinal bleeding from portal hypertension in cirrhosis: rationale for medical treatment.

We updated meta-analysis and critical descriptive analysis of randomized clinical trials (RCTs) assessing the value of beta-blockers in preventing first bleeding (prophylactic) or rebleeding (therapeutic) and on survival of patients with cirrhosis. Both the methods of Peto-Mantel-Haenszel and DerSimonian-Laird were used to assess the heterogeneity and obtain cumulative estimates of treatment effects; the L'Abbé plot was also used for a visual assessment of heterogeneity in the direction of treatment effect. Seven prophylactic and nine therapeutic RCTs were analysed. beta-Blockers uniformly reduced the bleeding risk and revealed a trend toward improved survival in non-ascitic, well-compensated patients in both the prophylactic and therapeutic sets of RCTs. Discordant results were found in patients with ascites or in poor functional condition.

Adrenergic beta-Antagonists↗
PubMed1991

Transmission of hepatitis B and hepatitis delta viruses in the households of chronic hepatitis B surface antigen carriers: a regression analysis of indicators of risk.

To evaluate whether clinical and laboratory features of a hepatitis B surface antigen (HBsAg) carrier can predict risks of infection, its chronicity, and the development of liver disease among close contacts, the authors studied a cohort of 994 first degree relatives or cohabitants (household contacts) of 226 non-drug-addicted chronic HBsAg carriers (index cases), of whom 77% had liver disease and 26% were superinfected by hepatitis D virus (HDV). A logistic form of regression analysis was used to assess the role of each feature in the index case as predictor of hepatitis B virus (HBV)- and HDV-related outcomes among household contacts. Six models of risk, expressed as odds ratios, were assessed by multivariate step-down analysis, with the following results. 1) Infection with HBV in the household contact was independently predicted by the index case being son, sibling, spouse, female, or HBV-DNA positive. 2) Chronic HBsAg carriage in the adult household contact was associated with female sex of the index case and with being a sibling; among young subjects, household contacts were more likely to be chronic HBsAg carriers when the index case was the mother, a sibling, or an HBV-DNA-positive subject. 3) HBV-DNA positivity in the young contact was more likely when the index case was HBV-DNA positive and when she was the mother. 4) HBV-DNA positivity in the absence of hepatitis B e antigen (HBeAg) in serum in the index case was not related to a similar pattern of infection in HBsAg-positive contacts. 5) Super-infection with HDV of an HBsAg-positive household contact was significantly predicted by female sex of the index case and by anti-HDV positivity. 6) Chronic liver disease in a contact was predicted only by HDV superinfection of the index case. We conclude that horizontal, nonparenteral transmission of HBV among siblings plays a major role in the household of HBsAg carriers from an intermediate endemicity area.

Adolescent↗
PubMed1991

Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group.

BACKGROUND: The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported. METHODS: In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo. RESULTS: After two years, the mean (+/- SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 +/- 3 percent in the beta-adrenergic-antagonist treatment group and 65 +/- 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 +/- 2 percent in the treatment group and 82 +/- 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 +/- 3 percent in the treatment group and 68 +/- 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 +/- 3 percent in the treatment group and 53 +/- 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P less than 0.001) and death (P less than 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P less than 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices. CONCLUSIONS: Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity.

Adrenergic beta-Antagonists↗
PubMed1991

Hepatocellular carcinoma. A worldwide problem and the major risk factors.

Male sex, age, cirrhosis, and HBsAg are the major risk factors for hepatocellular carcinoma (HCC). The geographic distribution of HCC is highly uneven, such that three distinct incidence areas are recognized. To clarify the reason(s) for this geographic variability of HCC, the risk factors in each incidence area were assessed. In parallel with the geographic distribution of HCC, HBsAg prevalence was highest in both HCC patients and in general population in Africa and Asia, where mothers of HCC patients are frequently HBsAg-positive, suggesting that hepatitis B virus hyperendemicity and perinatal infection account for the high HCC incidence in these areas. Cirrhosis, which is found on autopsy in 80% of the cases of HCC patients worldwide, is the most prevalent risk factor for HCC in areas where hepatitis B virus infection is less common. However, HBsAg carriage adds to the HCC risk carried by cirrhosis and explains the higher incidence of HCC in cirrhotics from Africa and Asia as well as elsewhere. Available data suggest that chronic HCV infection is a risk factor for cirrhosis and HCC. HBV vaccination should decrease HCC incidence rates worldwide; however, HCC prevention in regions where HBsAg carriage is infrequent may also require prevention of the other causes of cirrhosis in order for HCC rates to decline.

Carcinoma, Hepatocellular↗
PubMed1991

Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease.

Leukocyte adhesion molecules are important in cell-cell interactions of the immune system. Lymphocyte function-associated antigen 1 (cluster designation 11a) mediates interactions between T cells and mononuclear phagocytes through its ligand, the intercellular adhesion molecule 1 (CD54), whereas complement receptors 3 (CD 11b) and 4 (CD11c) are involved in complement-mediated phagocytosis. Expression of CD11 molecules and intercellular adhesion molecule 1 was studied in colonic biopsy specimens from 20 patients with inflammatory bowel disease and 10 normal controls. In normal colon, few mononuclear phagocytes expressed lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1 at high densities. The major adhesion molecule was CD11c. Thus, the largest population of normal colonic mononuclear phagocytes was represented by quiescent, resident macrophages with likely phagocytic function. In inflammatory bowel disease, mononuclear phagocytes showed only a slight increase in CD11a expression and no significant change in expression of CD11b and CD11c. By contrast, the percentage of mononuclear phagocytes expressing intercellular adhesion molecule 1 was increased from 6.9% +/- 3.9% in controls to 69.2% +/- 12.8% in ulcerative colitis (P less than 0.001) and to 45.7% +/- 22.8% in Crohn's disease (P less than 0.01), showing a close relationship with histological activity. The increased expression of intercellular adhesion molecule 1 in inflammatory bowel disease indicates a state of immunological activation induced by local release of inflammatory cytokines. Such induction of intercellular adhesion molecule 1 on mononuclear phagocytes may be important in the maintenance of chronic inflammation by facilitating interactions with T cells and T-cell antigen recognition.

Adult↗
PubMed1991

A performance evaluation of the expert system 'Jaundice' in comparison with that of three hepatologists.

The diagnostic performance of an Expert System (Jaundice) designed to discriminate between different causes of jaundice was evaluated in a test sample of 200 consecutive in-patients with serum bilirubin greater than or equal to 51 mumol/l. The average probability assigned to true diagnosis, the non-error rate and the overall accuracy were, respectively, 55%, 77% and 70%. The Expert System's discriminatory ability in probabilistic prediction, assessed by a method based on continuous functions of the diagnostic probabilities (Brier score) was good. We also compared the ability of our Expert System to that of three experienced hepatologists, who were required to give a diagnosis in 20 cases following the same protocol used by computer (i.e., by asking only clinical and laboratory items). Both the hepatologists and Jaundice achieved a correct diagnosis in 70% of 20 cases, but the Expert System asked a significantly higher average number of questions during each consultation. Analysis of the reasoning pathway made by an external referee showed a high agreement between the diagnostic strategies of the Expert System and the physicians. We conclude that Jaundice can be a useful tool to support a physician with insufficient clinical experience in this field to generate correct diagnostic hypotheses.

Diagnosis, Computer-Assisted↗
PubMed1991

Hepatitis C virus replication in 'autoimmune' chronic hepatitis.

Both high and low anti-hepatitis C virus antibody (anti-HCV) prevalence has been reported in autoimmune chronic active hepatitis. Therefore, we studied 15 consecutive HBsAg-negative, ELISA anti-HCV-positive, autoantibody-positive patients with biopsy proven chronic active hepatitis in order to confirm ELISA specificity by immunoblot test (RIBA-HCV), and to evaluate HCV replication by serum HCV-RNA. Nine patients were anti-nuclear, three type 1 anti-liver-kidney microsomal and three anti-smooth muscle antibody positive. None had associated autoimmune disease. All cases showed mild clinical disease and only moderate necroinflammatory activity. Response to prednisone was poor. RIBA-HCV confirmed ELISA results in all patients. HCV-RNA was found in the serum from 10 patients. Institution of alpha-interferon treatment in three steroid non-responsive patients was followed by prompt normalization of transaminases. Thus, a subgroup of autoantibody-positive chronic active hepatitis can be recognized as HCV-related and should be clinically and etiologically distinguished from autoimmune chronic active hepatitis. Trials of alpha-interferon treatment are worthwhile in this condition.

Autoantibodies↗
PubMed1991

Interferon for non-A, non-B chronic hepatitis. A meta-analysis of randomised clinical trials.

We reviewed randomised clinical trials evaluating the effect of lymphoblastoid or recombinant alpha-interferon in non-A, non-B chronic hepatitis. The outcomes assessed were the rates of serum alanine aminotransferase normalization and relapse during and after stopping interferon. Data were pooled by meta-analysis and a 50% overall rate difference, favouring treated patients, was found. Results showed homogeneity in direction of treatment effect both after short-term (2-6 months, greater than or equal to 2 mega-units thrice weekly) and long-term (9-18 months, variable dose) interferon course. Moreover, results did not change when type of publication (abstracts vs. full reports) and treatment duration or schedule were accounted for. About 50% of patients originally responding to treatment relapsed within 6 months of either dose reduction or stopping interferon, thus suggesting that only in about one out of four patients is benefit from treatment sustained up to 1 year. We conclude that larger trials are needed to identify an optimal schedule of treatment and to evaluate predictors of interferon effectiveness in patients with non-A, non-B chronic hepatitis.

Alanine Transaminase↗
PubMed1991

Is autoimmune chronic active hepatitis a HCV-related disease?

We evaluated the specificity and clinical relevance of anti-hepatitis C virus antibody positivity in 22 HBsAg-negative patients with autoimmune (anti-nuclear, anti-actin or anti-liver-kidney microsomal antibody positive) chronic active hepatitis. An ELISA anti-HCV test and a recombinant immunoblot assay (RIBA-HCV) were used. Thirteen patients (59%) were anti-HCV positive and five (23%) anti-HCV negative by both ELISA and RIBA-HCV tests. Four patients (18%) were borderline positive by ELISA (OD less than 1.0), and three of them (all with severe disease) were negative by RIBA. Histologic necroinflammation, AST/ALT and gamma-globulins levels were higher and response to prednisolone treatment was better in RIBA anti-HCV-negative than in anti-HCV-positive cases. We confirmed with both RIBA and ELISA tests the high prevalence of anti-HCV already reported by ELISA in anti-nuclear and anti-liver-kidney microsomal antibody positive chronic active hepatitis. False positive for anti-HCV (i.e., a positive ELISA test not confirmed by RIBA) occurred only among patients with severe disease. Since RIBA-negative subjects showed the best response to corticosteroid, they might represent the only subset of cases of 'true' autoimmune chronic active hepatitis.

Adrenal Cortex Hormones↗
PubMed1990

Natural history of congestive gastropathy in cirrhosis. The Liver Study Group of V. Cervello Hospital.

In a prospective study of the natural history of congestive gastropathy, 212 consecutive cirrhotic patients (75 treated with sclerotherapy) were included. Mean follow-up was 46 months. Mild gastropathy (mosaiclike pattern) was found in 110 patients and severe gastropathy (granular mucosa with cherry spots) was found in 20. Prevalence of Helicobacter pylori, formerly Campylobacter pylori, was 50% in patients without, 43% in those with mild, and 28% in those with severe gastropathy. Congestive gastropathy was significantly more frequent in patients treated with sclerotherapy (83% vs. 50%, P less than 10(-5)). Sixty-month actuarial proportions of patients free of anemia (in the absence of hematemesis or melena), were 17% with severe, 62% with mild, and 93% without gastropathy (P less than 10(-8]. Corresponding figures for overt bleeding were 25%, 73%, and 87% (P less than 10(-7], whereas those for survival were 46%, 72%, and 85% (P = 0.0005), respectively. A multivariate regression analysis supported the following conclusions: (a) sclerotherapy and the presence of large esophageal varices significantly increase the risk of congestive gastropathy, which (b) is a significant risk indicator of both chronic and overt bleeding but does not independently affect survival.

Adult↗