Norman B. Javitt

Cimetidine cholestatic jaundice in children

Patients. The children were 14, 3, 2, 1.5, and 1 year old (Table 1). The peptic disease was duodenal ulcer in three patients and prepyloric ulcer in two. Two patients had major duodenal ulcer hemorrhage at the time cimetidine therapy was instituted. The third patient with a duodenal ulcer had a 90% small bowel resection 3 months prior to the diagnosis of his ulcer. One of the children with a prepyloric ulcer had an associated hiatal hernia; the other had gastric outlet obstruction. Patients No. 1 and 3 had preexisting liver disease. The latter had biliary atresia treated by Kasai’s operation [3]; the etiology of the liver disease in patient No. 1 was never precisely diagnosed but could have been a consequence of long-term parenteral alimentation or chronic sepsis. Diagnosis of peptic disease was made by barium study and in two instances confirmed by endoscopy.

Chenodeoxycholic acid-3-sulfate: Metabolism and excretion in the rat and hamster and effects on hepatic transport systems☆

The metabolism and excretion of chenodeoxycholic acid-3-sulfate were determined in rats and hamsters. Constant intravenous infusions of 1, 2, and 3 mumoles/min in rats gave a maximum excretion in bile of 1.25 mumoles/min. Simultaneous infusions of sodium taurocholate at 2.0 mumoles/min and sulfobromophthalein at 0.2 mumole/min had no effects on the maximum excretion rate of chenodeoxycholic acid-3-sulfate. However, the bile acid ester sulfate caused a dose-related reduction in the excretion rate of BSP without affecting bile acid excretion rate and without a reduction in total bile flow. Chromatographic analysis of ester sulfate, a bile acid recovered in bile and urine, indicated that more than 95% had not undergone further metabolic transformation.

Biliary lipid excretion after hepatic portoenterostomy.

Since 1974, 16 consecutive infants with biliary atresia have been treated by hepatic portoenterostomy employing an exteriorized Roux-en-Y intestinal segment (Mikulicz). Simultaneous, sequential analyses of bile pigments and lipids in serum and biliary drainage were performed. In the 11 patients with sustained bile drainage, progressive increases in bile volume, bilirubin and biliary lipid concentrations correlated well with their subsequent return toward normal in the serum. Despite relief of biliary obstruction, four patients have had progressive liver cirrhosis. The other 7 have residual liver damage which has been stable, or in two instances, improved, at late biopsy. The clinical and biochemical results suggest that both obstructive and parenchymal factors are operative in infants with biliary atresia.

Current Status of Cholestasis Induced by Monohydroxy Bile Acids

The development of an experimental model for the induction of cholestasis (1) has led to further exploration of the pathophysiological mechanism and to a search for evidence that monohydroxy bile acids may be a cause of cholestasis in man.

Pathogenesis of Cholesterol Gallstones

The discovery that spontaneous gallstone formation occurs in the baboon provided an appropriate animal model for study of the relative contributions of the liver and gallbladder to cholelithiasis. Use of this model has shown that supersaturation of hepatic bile is normal during certain phases of the enterohepatic cycle and that local conditions within the gallbladder cannot be ruled out of the pathogenetic process.