Sclerosing cholangitis with neonatal onset.

Sclerosing cholangitis is characterized by irregular narrowing of extrahepatic or intrahepatic bile ducts, and in adults is defined mainly by radiologic findings. We describe eight children with cholestasis from the first week of life, followed by early cirrhosis and portal hypertension. Histologic examination of the liver showed absence of interlobular bile ducts in the early cholestatic phase in two patients and biliary cirrhosis later in all patients. Radiologic examination by percutaneous cholecystography under ultrasound guidance, carried out at age 8 months to 9 years, disclosed abnormal intrahepatic bile ducts with rarefaction of segmental branches, stenosis, and focal dilation. The extrahepatic ducts were involved in six patients. No intestinal disease has been found in these patients.

Alterations in cholesterol metabolism in cultured fibroblasts from patients with Niemann-Pick disease type C.

Cholesterol synthesis, esterification and efflux were investigated in cultured fibroblasts from patients with Niemann-Pick disease type C. Sterol synthesis from sodium acetate was markedly increased in the two Niemann-Pick disease type C strains as compared to controls, either in the presence or absence of exogenous cholesterol supply by low-density lipoproteins. By contrast, cholesterol esterification was about 2-3-fold reduced when measured by oleic acid incorporation into cholesteryl esters and 10-15-fold reduced when measured with labelled free cholesterol as precursor, although acylcoenzyme-A:cholesterol acyltransferase activity was normal when studied in vitro on cell homogenates. Chase experiments with 14C-cholesterol demonstrated that the rate of cholesterol efflux was decreased by about 3-4-fold in fibroblasts from patients with Niemann-Pick disease type C. These results provide further evidence for alterations of sterol metabolism in Niemann-Pick disease type C and support the hypothesis of a trapping of exogenous cholesterol, which cannot enter the regulatory intracellular pools.

[Changes in the biosynthesis, esterification and efflux of cholesterol in fibroblasts in culture from patients with Niemann-Pick disease type C]. / Altérations de la biosynthèse, de l'estérification et de l'efflux du cholestérol dans les fibroblastes en culture de sujets atteints de maladie de Niemann-Pick type C.

Cholesterol synthesis, esterification and efflux have been comparatively studied in control fibroblasts and in fibroblasts from patients with Niemann-Pick disease type C (NPC). Sterol synthesis was markedly increased in NPC cells as compared to controls, either in whole medium or in medium devoid of lipoproteins. 14C-oleic acid incorporation into cholesteryl-esters was 2 to 3 fold reduced in NPC cells, and esterification of 14C-exogenous cholesterol was dramatically (15-30 fold) decreased. ACAT activity, measured in vitro, was not significantly altered in NPC cells. Finally, cholesterol efflux appeared to be decreased in NPC fibroblasts as compared to controls. The hypothesis of a defect in exogenous cholesterol access to intracellular regulatory pools is proposed.

Prolonged constant rate elemental enteral nutrition in Crohn's disease.

Constant rate enteral nutrition (CREN) has been used in 17 pediatric patients with Crohn's disease. Exclusive CREN was maintained from 2 to 7 months and progressively reduced to assure fractioned oral intakes from 12 to 22 months. From this preliminary study, CREN appeared to be as effective as steroid therapy in initiating remission of active Crohn's disease and was able to suppress steroid dependence. In some cases with prolonged CREN, reduction or disappearance of stenotic lesions of the bowel was observed. Two other positive points must be emphasized: the favorable psychological impact of the method and the ability to avoid growth suppression secondary to steroids. The long-term effects and longer remissions must be confirmed by a multicenter study in a larger group of patients.