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To define the physiopathological significance of 201Tl per rectum scintigraphy, we compared results obtained using this method with direct measurement of inferior mesenteric shunting, portal pressure, liver cellular function as evaluated by the Aminopyrine Breath Test and the size of esophagogastric varices and spleen, constituting, respectively, indirect representation of azygos and splenic shunts. Results indicated that a high correlation exists between the measures of portal systemic shunt estimated by the per rectal method and those obtained by direct administration of the tracer in the inferior mesenteric artery. No correlation was observed between 201Tl per rectal results and portal pressure or with azygos and splenic shunting. Fair correlation was observed with the Aminopyrine Breath Test. This could be explained by the fact that both methods are altered in advanced liver disease. These results suggest that the 201Tl per rectal scintigraphy explores the portal systemic shunt, which depends almost exclusively on the inferior mesenteric territory. While the limited territory explored by the method constitutes, undoubtedly, a limiting factor in detection and quantitation of total portal-systemic shunt, the specific information provided by the test could be useful in defining clinical and biological profiles of cirrhotic patients with inferior mesenteric shunting.

In a long-term survival study, we compared the prognostic significance of the hepatic venous pressure gradient and of the aminopyrine breath test (ABT) in 99 alcoholic cirrhotic patients. Thirty patients survived and had a complete follow-up for at least 4 yr. Mean hepatic venous pressure gradient was 19.1 +/- 5.8 mm Hg (range 8-35 mm Hg). Variceal rupture occurred only when the gradient was > or = 12 mm Hg. Variceal bleeding was observed exclusively in patients with large varices. Survival was not influenced by the level of gradient. We used the ABT to classify patients into three groups (group I, ABT > or = 2%; group II, 1% < or = ABT < 2%; and group III, ABT < 1%). Survival was significantly higher in group I than in group II (p < 0.05) or III (p < 0.01), indicating a better prognosis at a residual functional hepatic cellular mass of about 50% of the lower limit of normal value.

Sixty-three outpatients with endoscopically proven duodenal ulcer and 58 with gastric ulcer were treated under single-blind conditions with either sucralfate, 4 g daily, or with cimetidine, 1 g daily. Endoscopy was performed after 4 weeks and again after 6 weeks if the ulcer had not healed. Among the duodenal ulcer patients, 22 of 31 (71.0%) who received sucralfate and 24 of 32 (75.0%) who received cimetidine were healed after 4 weeks. After 6 weeks, the overall healing rate was 96.8% in the sucralfate group and 96.9% in the cimetidine group. Of 28 gastric ulcer patients who received sucralfate, 10 (35.7%) were healed after 4 weeks, compared with 18 of 30 (60.0%) who received cimetidine. The overall healing rates after 6 weeks were 71.4% in the sucralfate group and 83.3% in the cimetidine group. None of the differences between treatment groups was statistically significant. No serious side effects occurred with either drug. The results suggest that sucralfate and cimetidine are equally effective in the short-term treatment of peptic ulcer.

The clinical value of thallium 201 per rectum scintigraphy in the work-up of patients with alcoholic liver disease was evaluated using data obtained in 104 patients. The 25th min ratio of heart to liver activities was used as an index of portal systemic shunting. This ratio was found to be normal in alcoholic patients with normal liver biopsy and also in those presenting only steatosis. It was slightly higher in patients with liver fibrosis and significantly higher values were observed in patients with liver cirrhosis. High values of the ratio were associated with a higher risk of portal systemic encephalopathy and/or gastrointestinal bleeding. The prognostic value of the test was supported by the fact that good correlations were observed between the ratio and widely accepted prognostic scores such as the Child score or the Orrego index. Moreover, high ratios were associated with an increased mortality risk at one year. We conclude that this simple test is interesting in the screening of cirrhotics at risk of encephalopathy, gastrointestinal hemorrhage, or early death.

To elucidate the mode of action of AC-3579, a diazafluoranthen derivative, the effects of the drug were tested, in incubations with rat liver homogenates on three phospholipases: the endogenous microsomal phospholipase A and the exogenous phospholipases A2 and C. The rates of hydrolysis of phosphatidylcholine and phosphatidylethanolamine, the main liver phospholipids, were significantly decreased in liver of treated animals. This inhibition was more marked in experiments with exogenous phospholipase A than with phospholipase C. For phospholipid the difference observed may be due to the decrease in activity of endogenous phospholipase A in livers of treated rats. On the other hand, the addition to the incubation media of AC-3579 or of homogenates of AC-3579-treated rat livers did not modify the action of the three phospholipases on phospholipids from normal rat liver homogenates. It is concluded that AC-3579 forms with the hydrophobic moiety of the phospholipids of smooth endoplasmic reticulum a reversible complex less accessible to the activity of phospholipase A. This mechanism accounts for the decrease in phospholipid catabolism, previously observed in vivo, which leads to hypertrophy of smooth endoplasmic reticulum and to the formation of lamellate cytosomes.

The effects of AC-3579 (NSC-170561), a new experimental antitumour drug which depresses phospholipid catabolism in liver, were compared in rat aflatoxin-induced hepatoma and in non-neoplastic hepatocytes surrounding the tumour. Ultrastructural lesions, characterized by the hypertrophy of the smooth endoplasmic reticulum and the presence of lamellate cytosomes appeared in both tissues. They were less marked in hepatoma than in non-neoplastic cells. As in control livers, they were related to an invrease in pohspholipid concentration due to the decrease of phospholipid breakdown. In addition, chemical analysis demonstrated differences between hepatoma, non-neoplastic aflatoxin-treated liver and control liver: total and free cholesterol were decreased, relative concentration of sphingomyelin increased and that of phosphatidylethanolamine decreased by about 50%, in both hepatoma and non-neoplastic liver. Phospholipid concentration was decreased by 50% in tumour cells. After AC-3579 treatment total cholesterol was increased 3.2 fold in non-neoplastic liver and 2.5 fold in hepatoma but not in control liver.