Pharmacokinetics and safety of single oral doses of amlodipine in patients with and without hepatic impairment: an open study.

An open study was conducted to assess the pharmacokinetics, cardiovascular effects and safety of a single oral dose of amlodipine 5 mg in 12 patients with hepatic impairment and eight healthy convalescing subjects. Cmax values were found to be similar in both groups although Tmax was shorter, and T1/2 was longer, in patients with hepatic insufficiency. AUCs were also higher in hepatic patients although these differences were not significantly different. No side-effects or cardiovascular/ECG changes were observed in either group. Three patients with hepatic failure experienced mild laboratory abnormalities which were of doubtful clinical significance.

[Hepatocellular carcinoma with cirrhosis: treatment with doxorubicin. Phase II evaluation]. / Carcinome hépatocellulaire sur cirrhose: traitement par la doxorubicine. Essai phase II.

Twelve patients with unresectable hepatocellular carcinoma associated with cirrhosis were treated with Doxorubicin which was given intravenously (30 to 50 mg/m2) every three weeks. Six patients were given only one dose of Doxorubicin. No clinical response was observed. Five patients has serum alphafoetoprotein (AFP) determination during the treatment. AFP concentration rose in 4 patients and fell in 1 patient. Survival rate after 3 and 8 months of treatment was 58 and 33 per cent. These results suggest that Doxorubicin is not an effective treatment for hepatocellular carcinoma.

[The liver and metabolism of drugs]. / Fegato e metabolismo dei farmaci

Even if all problems of liver metabolism have not yet been clarified, it is nevertheless established that medicaments induce enzymes in the hepatic cells which influence the metabolism of drugs. Because their effect is unspecific, these enzymes can catabolize many drugs with different structures. About 200 substances are known which induce such enzymes. Among them, for example, is phenobarbital. It is therefore used in the treatment of some forms of icterus with free bilirubin and for Cushing's syndrome. But enzyme induction can also lead to acute intermittent porphyrias and disturbances of the phosphorus-calcium metabolism. Extreme catabolism of a drug can be caused by overinduction of enzymes due to the administration of several incompatible medicaments.

[Cholesterol crystals, cholesterol saturation of bile and biliary lithiasis]. / Cristaux de cholestérol, saturation de la bile en cholestérol et lithiase biliaire.

UNLABELLED: It has been repeatedly shown that normal human gallbladder bile is commonly supersaturated wih cholesterol. It has been therefore suggested that the crucial step of the formation of cholesterol gallstones might be the nucleation and growth of cholesterol monohydrate crystals. Consequently this work was aimed at determining: 1) if cholesterol crystal formation is really a typical feature of gallbladder bile with cholesterol gallstones; 2) the influence of the degree of cholesterol saturation of bile on the formation of cholesterol crystals. Gallbladder bile from 89 patients (23 from patients with cholesterol gallstones, 7 from patients with non-cholesterol gallstones and 59 from patients free of gallstones) and hepatic bile from 17 previously cholecystectomized patients were studied. Four of these patients had cholesterol stones of the common bile duct. RESULTS: (a) gallbladder bile: cholesterol crystals were present on immediate examination in 19 of the 23 bile samples with cholesterol stones, in 2 of the 7 bile samples with non-cholesterol stones and in 1 of the 59 bile samples without stones. Only 1 bile sample with cholesterol stone developed crystals. Cholesterol saturation of bile with or without crystals did not differ significantly; (b) hepatic bile: cholesterol crystals were detected on immediate examination in one of the 17 bile samples and subsequently appeared in one of the remaining samples. Cholesterol saturation of hepatic bile (2.10 +/- 0.43) was significantly higher (p less than 0.01) than that of gallbladder bile containing cholesterol stones (1.32 +/- 0.43).(ABSTRACT TRUNCATED AT 250 WORDS)

[Ascites disclosing systemic lupus erythematosus]. / Ascite révélatrice d'un lupus érythémateux disséminé.

We report the case of a 38-year old woman with massive ascites. No cause could be demonstrated despite multiple investigations. The patient was febrile and had an elevated erythrocyte sedimentation rate. Systemic lupus erythematosus was subsequently diagnosed, when malar rash, arthritis, leucopenia, anti-native DNA and anti-Sm antibodies appeared. Ascites and lupus manifestations resolved simultaneously on steroid therapy. This unusual cause of ascites should be recognized, since it responds favorably to steroid therapy.

[Superficial and extensive epidermoid cancer of the esophagus]. / Cancer épidermoïde, superficiel et étendu en nappe, de l'oesophage.

A case of extensive squamous cell carcinoma of the esophagus in a 56 year old man, with an history of excessive alcoholic and tobacco consumption, is reported. After subtotal esophagectomy, the course was favorable 10 months after surgery. The pathological study of the surgical specimen showed that the tumor was superficial and confined to the mucosa and submucosa. The lesion measured 65 mm in length (after fixation) and was circumferential. Foci of moderate and severe dysplasia and inflammatory erosions were also observed. The relationship between extensive squamous cell carcinoma, dysplasia, esophagitis and the concept of "carcinogenic fields" are discussed. The necessity of large radical resection of the esophagus is emphasized.

[Hepatitis and pancreatitis due to indalpine]. / Hépatites et pancréatite à l'indalpine.

The authors report two cases of hepatitis and a case of pancreatitis associated with indalpine. In one case of hepatitis, onset was acute and the clinical presentation was suggestive of cholecystitis; in the other case, hepatitis was discovered by biological tests. In the two cases, hepatitis was mainly cytolytic. Outcome was favorable upon interruption of drug administration. Onset of pancreatitis was inconspicuous, with progressively increasing pain. The pancreatic lesions were diffuse and massive. After interruption of administration, outcome was eventually favorable. Elevated amylasemia was also noted in the two cases of hepatitis. It is suggested that transaminase and amylase activities should be monitored during indalpine therapy.

[Nodular regenerative hyperplasia of the liver and primary biliary cirrhosis. A fortuitous association?]. / Hyperplasie nodulaire régénérative du foie et cirrhose biliaire primitive. Une association fortuite?

We report here in a case of primary biliary cirrhosis associated with nodular regenerative hyperplasia of the liver in a white woman revealed by digestive hemorrhage due to ruptured esophageal varices. The diagnosis of primary biliary cirrhosis was based on the following: elevated serum IgM, high titer of antimitochondrial antibody (anti M2), typical histopathological picture of stage I/II disease. The diagnosis of nodular regenerative hyperplasia was supported by the demonstration of disseminated small hepatic nodules without perinodular fibrosis. This association may be a supplementary argument in favor of a possible autoimmune origin of nodular regenerative hyperplasia of the liver.

[Does the size of esophageal varices have a prognostic significance in alcoholic cirrhosis?]. / La taille des varices oesophagiennes a-t-elle une signification pronostique au cours des cirrhoses alcooliques?

This study was designed to determine whether the size of esophageal varices were of prognostic value in patients with alcoholic cirrhosis. Esophageal varices were classified into 2 groups according to whether their size was larger or smaller than 4 mm. There was a total of 99 patients; 56 had small varices and 43 had large varices. Of the clinical and biological data collected at the time of determination of the size of the esophageal varices, only the duration of cirrhosis and the prevalence of gastrointestinal bleeding were significantly greater in patients with large esophageal varices. The one- and two-year cumulative rates of patients with large esophageal varices were 63 +/- 7 p. 100 and 42 +/- 8 p. 100, respectively; these results were not significantly different from those in patients with small esophageal varices, i.e. 68 +/- 6 p. 100 and 61 p. 100 respectively (p less than 0.5 for one-year survival; p less than 0.08 for two-year survival). Serum bilirubin and albumin as well as the presence of ascite were of significant prognostic value concerning death at two years while the presence of esophageal varices did not significantly increase the prognostic value of the above-mentioned variables (using Cox's regression model). In conclusion, the results of our study suggest that large esophageal varices, in spite of their association with a high incidence of gastrointestinal bleeding, do not influence prognosis at two years for patients with alcoholic liver cirrhosis.

[Hepatic function and significance of the increase in serum concentrations of IgA in alcoholic cirrhosis]. / Fonction hépatique et signification de l'augmentation de la concentration sérique des IgA au cours de la cirrhose alcoolique.

Elevated serum gammaglobulin concentrations are frequently observed in patients with liver cirrhosis. Predominant elevation of the IgA is generally considered as suggestive of an alcoholic aetiology. The aim of this study was to define the factors that determine the serum concentration of IgA in alcoholic cirrhosis. Twenty-seven patients with alcoholic cirrhosis were studied. Serum concentrations of IgG, IgA and IgM were measured by immunonephelometry. Hepatocellular function was assessed by the Child-Turcotte score, the prothrombin time and the intrinsic clearance of indocyanine green. The importance of intra-hepatic shunts was estimated according to the intact hepatocyte theory, and the degree of hepatic necrosis by serum levels of transaminases. It was noted that: 1) the IgA concentration correlated significantly with the Child-Turcotte score and with the decrease of the prothrombin time, intrinsic clearance and the functional fraction of hepatic blood flow; 2) there was no such correlation between the serum concentration of IgA and the total hepatic blood flow or transaminase levels; 3) there was no correlation between serum concentration of IgG or IgM and the factors studied. These results suggest that in alcoholic cirrhosis, increase in serum IgA, reflects the degree of impairment of hepatic function and intrahepatic shunting.

[Extensive liver cancer of undetermined origin. Diagnostic procedure]. / Cancer étendu du foie d'origine indéterminée. Conduite diagnostique.

In patients with isolated malignant tumoral hepatomegaly, the investigations performed should aim at excluding a primary carcinoma of the liver and concentrate on the search for primary tumours belonging to 2 main groups: tumours responsive to hormonal treatment or chemotherapy, and obstructive tumours amenable to local palliative measures. In all cases where simple, essentially clinical examinations fail to indicate the cause of the tumoral liver enlargement, further investigations should be based on the histopathological features of the metastases.

[Current etiological problems, in France, related to primary liver cancer in cirrhosis (personal observation of 130 cases)]. / Problèmes étiologiques actuels posés, en France, par le cancer primitif du foie développé sur cirrhose (à propos de 130 observations personnelles).

The etiological problems concerning, in France, hepatocellular carcinoma (H C C) developed on liver cirrhosis, are studied in this work through 130 personal cases followed up during the last decade. These 130 cases of H C C are divided in five groups according to apparent etiology: alcoholic (63%), B virus (15.3%), cryptogenetic (11,5%), hemochromatic (7.6%), autoimmune (2.3%). A review of these cases according to recent publications shows an evidence underestimated for years: we mean the important role played in France by H B V (and probably H C V) not only in chronic cirrhotic hepatitis, but even more in cancerization of cirrhosis in general whatever is the apparent etiology. This role, unsuspected when biological investigations are limited to serological markers of H B V, is demonstrated by implementing more sophisticated+ technics (molecular hybridization+ and gene amplification). But it is very unlikely that this role is exclusive++ and one must recognize that viral "focalization" of recent publications has a tendency to hide other causes of H C C and primarily the toxicological etiology in a wide sense. This etiology is in fact indubitable, already in tropical areas, where the role of mycotoxins and particularly of aflatoxin B l is very well demonstrated, even in areas of very high incidence of H B V. In low incidence areas, such as France, the specific carcinogenic role of alcohol cannot be excluded, neither the role of numerous experimental hepato-carcinogen, very much studied 15 years ago and may be incorrectly forgotten in our days. If the accidents of research lead to privilege temporarily one or the other factor, one must not forget that the genesis of H C C is most probably multifactorial, as for the majority of human cancers.

Rioprostil in the short-term treatment of duodenal ulcer: a multicentre double-blind trial vs. cimetidine.

The efficacy and safety of the new prostaglandin E1 (PGE1) synthetic analogue, rioprostil, 300 micrograms b.d. and cimetidine, 400 mg b.d., on duodenal ulcer healing are compared in an international, multicentre, double-blind study. A total of 257 patients have entered the study; 243 are considered eligible for efficacy analysis and 207 for safety analysis. After 4 and 6 weeks of treatment, the endoscopic healing rates do not significantly differ between the two groups, being 55% and 83% respectively with rioprostil vs. 60% and 78% respectively with cimetidine. The major adverse effect attributable to rioprostil is diarrhoea, which was documented in 11% of patients compared with 1% of patients taking cimetidine. However, central nervous system complaints are twice as frequent in the cimetidine group. Monitoring of clinical laboratory tests show no significant abnormalities when compared with the baseline values during the administration of either drug. This study documents that rioprostil, at the dosage of 300 micrograms b.d., is as effective and safe as cimetidine in the short-term therapy of duodenal ulcer.