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Biomedical subjects

T Poynard

Publications and source records attributed to T Poynard.

At least 163 records · Page 9Linked to original sources

Prednisone-interferon combination in the treatment of chronic hepatitis B: direct and indirect metanalysis.

The aim of this study was to review all published randomized clinical trials evaluating the efficacy of a combination of prednisone and interferon in treatment of chronic hepatitis B and to subject these studies to metanalysis. Two types of metanalyses were carried out: direct metanalysis, comparing the prednisone-interferon combination with interferon on its own; and indirect metanalysis, comparing the treatment efficacy of prednisone-interferon and of interferon with control results. At the end of follow-up, four assessable end points were analyzed: HBeAg, hepatitis B virus DNA, HBsAg loss and serum ALT normalization rate. The direct metanalysis included seven trials comparing prednisone-interferon with interferon treatment. No significant differences were observed between the two types of therapy, for all the criteria given. However, in patients with low ALT levels, the prednisone-interferon combination gave significantly better results than interferon alone--HBeAg loss was 48% in the former group vs. 18.4% with interferon alone (p < 0.01). Fifteen trials compared interferon with control values; all end points were significantly improved. Seven trials compared prednisone-interferon with control results and showed all end points to be significantly improved by treatment. Indirect metanalysis showed that the differences in odds ratios for prednisone-interferon/control group and interferon/control group studies were negative for all assessable end points. In conclusion, the use of corticosteroids did not produce any significant increase in the efficacy of interferon treatment in adults with chronic hepatitis B and high initial ALT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Alpha-2-macroglobulin and hepatic fibrosis. Diagnostic interest.

Alpha-2-macroglobulin (A2M) is a proteinase inhibitor. Cells synthesizing A2M are in first-order hepatocytes and in second-order activated Ito cells (in culture starting at day 4-5 after seeding). This study was undertaken in 525 alcoholic patients with different histological stages of alcoholic liver disease to assess if the A2M could improve the diagnostic value of PGA index for detection of cirrhosis or fibrosis among drinkers, particularly in patients without clinical symptoms of liver failure and portal hypertension, and to assess the specific correlation of serum A2M with the score of liver fibrosis adjusted for steatosis and alcoholic hepatitis and thereafter adjusted for GGT, PT, and ApoA1, the three components of the PGA index. In 525 alcoholic patients, we have demonstrated the independent diagnostic value of A2M. The predictive values of the weighted score, using linear discriminant function combining PT, GGT, ApoA1 and A2M of the PGAA score and of the PGA score were assessed in a training step and validated in a second step. Then, 316 alcoholic clinically asymptomatic patients were studied. In these patients, the discriminant function permitted correct classification of 72% of patients. The PGAA index had comparable diagnostic value with 70% of patients correctly classified. On the other hand, the PGA index including only PT, GGT, and ApoA1 had classified correctly less patients (65%) than the discriminant function and the PGAA index (P < 0.01). For a value of 7, PGAA had 79% specificity and 89% sensitivity for the diagnosis of cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

A two-centre, randomized, double-blind trial of ornithine oxoglutarate in 194 elderly, ambulatory, convalescent subjects.

In a double-blind trial, 194 ambulatory elderly patients (mean age, 74 +/- 8 years) recovering from acute illnesses were randomly assigned to receive either ornithine oxoglutarate (OGO) or a placebo. Nine subjects withdrew during the study, six in the OGO group and three in the placebo group. OGO and the placebo were administered once daily at a dose of 10 g after lunch for 2 months; the patients were monitored for a total of 4 months. Efficacy was evaluated in terms of nutritional variables, quality of life and total cost of medical treatment. The analysis involved a total of 185 patients (93 in the placebo group and 92 in the OGO group). The two groups were comparable at inclusion. After 30 and 60 days of treatment, there was a significant improvement in the following variables in the OGO group relative to the placebo group: appetite (p < 0.001), body weight (p < 0.001) and independence (p < 0.01). Two months after the end of treatment, there was still a significant improvement in the quality-of-life index (p < 0.001) and the medical-cost index (p < 0.03) in the OGO group, with an overall cost saving of 37%. We conclude that OGO seems to be a cost-effective nutritional supplement for elderly convalescent patients.

Activities of Daily Living↗

Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome.

AIM: To assess the efficacy of smooth muscle relaxants in the treatment of patients with irritable bowel syndrome, a meta-analysis of 26 selected double-blind randomized trials vs. placebo was performed. METHODS: Five end-points were assessed: global assessment, abdominal pain, constipation, abdominal distension and the absence of adverse reactions. Analyses were performed according to the intention-to-treat method. For each end-point, the drug efficacy was assessed by the Der Simonian and Peto methods. When a significant difference was observed, sensitivity analyses were performed by successive stratifications according to the type of drug, the treatment duration, the prevalence of constipated patients, the trial design and the methodological quality. RESULTS: All myorelaxants analysed were significantly better than placebo for the improvement of global assessment (62% improvement rate vs. 35% on placebo, that is 27% improvement rate, P < 0.01) and for pain improvement (64% improvement rate vs. 45% on placebo, that is 19% improvement rate, P < 0.01). No significant differences were observed for constipation and abdominal distension. The percentage of patients with adverse reactions was significantly higher in patients receiving myorelaxants than placebo (6% mean difference, P < 0.01). CONCLUSION: According to this overview five drugs have proved their clinical efficacy in patients with irritable bowel syndrome, without significant adverse reactions: cimetropium bromide, pinaverium bromide, trimebutine, octilium bromide and mebeverine.

Colonic Diseases, Functional↗

Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy.

OBJECTIVES: This meta-analysis was performed to determine whether corticosteroid therapy induces the development of peptic ulcer and other putative complications of steroid therapy. DESIGN: A retrospective investigation in which we analysed all the randomized, double-blind, controlled trials (RDBCT) in which steroids had been administered that we were able to identify. The number of episodes of peptic ulcer, dermatological effects, sepsis, diabetes, hypertension, osteoporosis, psychosis and tuberculosis reported in both the placebo and steroid groups were compared. SETTING: The international medical literature was analysed for any RDBCT in which any steroid or ACTH had been administered in any dosage for any duration, and any putative complication of steroid therapy was reported. SUBJECTS: Of 1857 articles, 93 satisfied our requirements and were analysed by the meta-analytic techniques of Peto, DerSimonian and Laird. A total of 6602 patients were included. MAIN OUTCOME MEASURES: The relative frequencies of each of these eight 'complications' were compared in the placebo and steroid groups using conventional statistics and meta-analysis. The relative frequencies of 'annualized' subgroups of patients who received treatment for 1 to 7 days, 1 week to 1 month, 1 to 3 months and more than 3 months, were similarly analysed. RESULTS: Nine of 3267 patients in the placebo group (0.3%) and 13 of 3335 patients in the steroid group (0.4%) were reported to develop peptic ulcer (P > 0.05). The dermatological cosmetic effects of steroid therapy were observed more frequently in the steroid group (P < 0.001), as was diabetes (P < 0.001), hypertension (P < 0.01) and psychosis (P < 0.001). Sepsis, osteoporosis and tuberculosis all occurred more frequently in the steroid than in the placebo group, but the differences are not statistically significant. CONCLUSIONS: Peptic ulcer is a rare complication of corticosteroid therapy that should not be considered a contraindication when steroid therapy is indicated.

Adrenal Cortex Hormones↗

Acetaldehyde-modified epitopes in liver biopsy specimens of alcoholic and nonalcoholic patients: localization and association with progression of liver fibrosis.

Acetaldehyde, the first product of ethanol oxidation, has been shown to stimulate collagen gene expression and to form protein-acetaldehyde adducts. Because little is known about these adducts in human liver tissue, we assessed, with an immunohistochemical procedure, the presence and location of acetaldehyde-protein adducts in liver biopsy specimens of alcoholic patients. In addition, we correlated the presence of adducts with the progression or subsequent occurrence of liver fibrosis. The group included 106 patients with high alcohol consumption (> 90 gm ethanol/day for the last 5 yr), 10 nonalcoholic patients with normal livers and 23 patients with other liver diseases. Sixty-four of the 106 alcoholic patients had a second liver biopsy, whose specimen was used to assess the progression of liver fibrosis. Polyclonal antibodies were produced against homologous low-density lipoprotein purified from rabbit serum and modified in vitro in the presence of acetaldehyde. Protein-acetaldehyde adducts could be detected by immunohistochemistry in biopsy specimens of 90 alcoholic patients (85%), in none of the 10 nonalcoholic patients with normal livers and in 65% of the patients with nonalcoholic liver disease. Acetaldehyde-modified epitopes were detected in the intracellular and extracellular compartment. Intracellular protein-acetaldehyde adducts were localized in the cytoplasm of hepatocytes with a more intense staining in zone 3. No correlation existed between the intensity of intracellular staining and the histologically assessed severity of liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

Meta-analysis of hydroxyethylrutosides in the treatment of chronic venous insufficiency.

The efficacy of O-(beta-hydroxyethyl)-rutosides (HR) in chronic venous insufficiency (CVI) was assessed by using a meta-analysis on the basis of randomized trials. Analyzed parameters were clinical symptoms related to CVI, i.e. pain of the legs, nocturnal cramps, tired legs, swelling sensations and restless legs. The treatments had to be administered for at least 4 weeks and the average HR dose chosen was 1000 mg/day. On a total of 21 evaluated trials, 15 were selected that included 1973 patients. The placebo-treated group showed a significant (p < 0.01) improvement of patients (i.e., disappearance of the symptoms) as follows: pain 27%, cramps 26%, tired legs 22%, swelling 35% and restless legs 26%. Compared to placebo, the mean additional improvement in favour of HR was 11% for pains, 12% for cramps, 12% for restless legs, 14% for swelling and 24% for tired legs. All these improvements were significant (p < 0.01). The results were robust and stood up to the treatment effect to all meta-analyses across subgroups of randomized clinical trials. In conclusion, this meta-analysis shows that, despite the high response rate to placebo therapy, the effect of HR therapy is significantly superior in the treatment of symptoms related to CVI.

Adult↗

Diaphragm function is not impaired by pneumoperitoneum after laparoscopy.

Open cholecystectomy is known to induce a major restrictive respiratory syndrome. These respiratory disturbances, although of reduced magnitude, still persist after laparoscopic cholecystectomy. To determine the role of pneumoperitoneum per se in the respiratory dysfunction observed after this procedure, seven patients were studied before and 2 hours after laparoscopy. This diagnostic procedure avoids the upper midline incision and the surgical injury of cholecystectomy. Ventilatory performance and diaphragm function were assessed as follows: (1) during quiet tidal breathing by obtaining measurements of esophageal, gastric, and transdiaphragmatic pressures; determining the ratio of gastric pressures to esophageal pressures; and abdomen-rib cage partitioning of tidal volume obtained from two differential linear transformers and (2) during maximal respiratory efforts by obtaining measurements of vital capacity and maximal transdiaphragmatic pressure during Müller's maneuver and a sniff test. Although a large residual pneumoperitoneum (assessed as the maximal height of the suprahepatic space: Hmax = 30.3 +/- 7.8 mm) was observed after laparoscopy, we did not find any change suggestive of diaphragm dysfunction. We thus conclude that postoperative residual pneumoperitoneum per se is unable to explain the diaphragm dysfunction observed after open or laparoscopic cholecystectomy.

Cholecystectomy, Laparoscopic↗

Relapse rate of patients after healing of oesophagitis--a prospective study of alginate as self-care treatment for 6 months. French Co-operative Study Group.

In order to estimate the rate of symptomatic relapse and to identify factors associated with this relapse, 1030 patients were included in a multicentre study. All patients included had clinically and endoscopically healed oesophagitis (grade I (erosion, 57%), grade II (confluent erosion, 33%) or grade III (circular erosion, 9%)) after treatment with an H2-blocker or omeprazole. Patients were given conservative advice and were told to take sodium alginate only in response to pain. Relapse was defined as pain justifying more than eight sodium alginate sachets over 48 hours or treatment with another drug, or the need for a new endoscopy. Forty risk factors were recorded initially and patients were seen every 2 months; they filled out diary-cards describing symptoms and drug consumption. Data were available for 883 patients during follow up. The cumulative percentage of patients without relapse at 6 months estimated by Kaplan Meier method was 76 +/- 2% (mean +/- S.E.M.). Among these patients without relapse, 95% took less than two sachets per day. Only two factors were identified as associated with relapse--the grade of oesophagitis (P < 0.007), and the occurrence of stress during follow-up (P < 0.05). The percentage of patients free from relapse at six months was 85 +/- 2% in patients with grade I oesophagitis, 69 +/- 3% in patients with grade II, and 56 +/- 6% in patients with grade III oesophagitis (P < 0.0001).

Adolescent↗

Transforming growth factor beta 1: in situ expression in the liver of patients with chronic hepatitis C treated with alpha interferon.

In a semiquantitative assessment of the expression of transforming growth factor (TGF) beta 1 in liver biopsy specimens from patients with chronic hepatitis C, treatment with interferon alfa-2b (3 million units (MU) three times weekly) decreased the expression of TGF beta 1 in six of seven patients. The reduction in TGF beta 1 correlated significantly with the scores for inflammation (p < 0.05) and necrosis (p < 0.05), but not with the alanine aminotransferase activities (p = 0.36) or the score for fibrosis (p = 0.86).

Adult↗

A randomized trial of prednisolone in patients with severe alcoholic hepatitis.

BACKGROUND: Controlled trials have yielded inconsistent results with regard to the efficacy of corticosteroids in the treatment of alcoholic hepatitis. Three meta-analyses suggest that they may be effective in patients with encephalopathy who have severe liver disease. METHODS: We conducted a randomized, double-blind trial comparing 28 days of prednisolone treatment (40 mg per day) with placebo in 61 patients with biopsy-proved alcoholic hepatitis and either spontaneous hepatic encephalopathy (n = 19) or a discriminant-function value higher than 32. The discriminant function used was as follows: 4.6 (prothrombin time-control time [in seconds]) + serum bilirubin (in micromoles per liter)/17. Fifty-seven of the patients had evidence of cirrhosis on biopsy. The primary end point was death within two months. RESULTS: One patient was lost to follow-up after 56 days. Treatment was discontinued in two patients because of drug toxicity. By the 66th day after randomization, 16 of 29 placebo recipients had died (mean [+/- SE] survival, 45 +/- 8 percent), as compared with 4 of 32 prednisolone recipients (survival, 88 +/- 5 percent) (log-rank test, 10.9; P = 0.001). The survival advantage for prednisolone persisted after stratification according to center and the presence of encephalopathy, and after adjustment for prognostic factors in a proportional-hazards model. CONCLUSIONS: Treatment with prednisolone improves the short-term survival of patients with severe biopsy-proved alcoholic hepatitis.

Double-Blind Method↗

Anti-pre-S responses and viral clearance in chronic hepatitis B virus infection.

Serial sera were collected prospectively during the clinical course of 13 HBsAg carriers with chronic liver disease and analyzed for ALT levels, pre-S1 and pre-S2 antigens and corresponding antibodies and other serological hepatitis B virus markers. In five patients, anti-pre-S1 and anti-pre-S2 antibodies became detectable in multiple serum samples, whereas in eight patients anti-pre-S was never detected or only appeared transiently during the follow-up. The first pattern was associated with normalization of ALT levels and undetectable pre-S antigens and viral DNA by the polymerase chain reaction assay at final follow-up. HBsAg clearance occurred in two of the five patients. The second pattern was one of persistence of HBsAg and pre-S antigens, associated with the presence of serum HBV DNA detectable by spot hybridization or polymerase chain reaction regardless of clinical outcome. These findings demonstrate the occurrence of anti-pre-S antibodies in chronic hepatitis B virus-induced liver disease and associate anti-pre-S appearance with the clearance of hepatitis B virus from serum.

Adult↗

Does elective sclerotherapy improve the efficacy of long-term propranolol for prevention of recurrent bleeding in patients with severe cirrhosis? A prospective multicenter, randomized trial.

We conducted a prospective, multicenter, randomized trial to compare the efficacy of sclerotherapy plus propranolol with that of propranolol alone in the prevention of recurrent gastroesophageal bleeding in severely cirrhotic patients. For 2 yr (1987 to 1988) 131 patients (96% of whom were alcoholic) with Child-Pugh class B or C cirrhosis (56% were class B and 44% were class C) were randomly assigned to one of our two treatment groups after cessation of variceal bleeding, without hemostatic sclerosis, and were observed for at least 2 yr. Treatment observance was good in 89% of cases; alcohol withdrawal was observed in 62% of cases. Sclerotherapy was performed weekly with 1% polidocanol, and variceal obliteration was obtained in 83% of cases, in a mean number of four sessions. The cumulative percentages (expressed as mean +/- S.D.) of recurrent bleeding at 2 yr were 42% +/- 6% for propranolol plus sclerotherapy and 59% +/- 6% for propranolol alone (a nonsignificant difference). Twenty-eight patients from the propranolol group but only 12 patients from the propranolol-plus-sclerotherapy group had recurrent bleeding from esophageal variceal rupture (p less than 0.01). The total number of blood units per patient with recurrent bleeding was slightly but not significantly more important in the propranolol group (8 +/- 7) than in the propranolol-plus-sclerotherapy group (5 +/- 5; p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal Diseases↗

Cirrhosis as an independent risk factor for colonic adenomas.

This study aimed to determine the relation between cirrhosis and colorectal adenomatous polyps after adjustment for alcoholism and other confounding variables. Four groups of patients aged 40 years or above were studied. Group I included 100 consecutive outpatients with irritable bowel syndrome, group II 100 consecutive alcoholic inpatients without cirrhosis, group III 100 consecutive inpatients with alcoholic cirrhosis, and group IV included 36 consecutive inpatients with non-alcoholic cirrhosis. All patients underwent colonoscopy. The prevalence of adenomatous polyps was 13% in group I, 26% in group II, 58% in group III, and 22% in group IV (p less than 0.001). The prevalence of adenomatous polyps was greater in patients with cirrhosis than in those patients without (48.5% v 19.5%). This difference remained significant after successive adjustment for alcoholism, sex, age, smoking, and serum cholesterol. The prevalence of adenomatous polyps was greater in alcoholic patients than in non-alcoholic patients (42% v 15.4%) (p less than 0.001). This difference remained significant after successive adjustment for cirrhosis, sex, age, smoking, and serum cholesterol. These results suggest that cirrhosis is an independent risk factor for colorectal adenomatous polyps and confirm that alcoholism increases this risk.

Adult↗