A sample of 126 patients with cholelithiasis was treated with chenodeoxycholic acid (CDCA) (375 or 750 mg g.d.) for 2 years. Hepatotoxicity was assessed by sequential light (LM) and electron microscopic (EM) analysis of liver biopsies obtained before and after 9 and 24 months of therapy. Patients were without symptoms of biliary colic for 3 months prior to biopsy, less than 70 years old, and had normal tests of liver function. All light microscopy was read blindly by two morphologists, and electron microscopy by one. Only four biopsies (3%) showed severe (3+) abnormalities preventing admission to the study. On evaluation, moderate (2+) LM changes were present in less than 12% of biopsies, while milder changes (1+) were seen more frequently. No severe, dose-related abnormalities were seen in LM over the 2 years of study. However, mild changes (hepatocyte ballooning and lipofuscin, binucleate cells, glycogen nuclei, ductular proliferation, enlarged and fibrotic triads, and sinusoidal congestion) became more prevalent with time (p less than or equal to 0.01) regardless of CDCA dose, according to 1 of the 2 morphologists. Because patients with "proven" cholelithiasis for greater than 2 years (33% of the study population) did not have a greater incidence of morphologic abnormalities than those with the diagnosis for less than 2 years, it is unlikely that these changes were due to the natural history of gallstone disease. Furthermore, electron microscopic findings demonstrated worsening intrahepatic cholestasis and a lesion in two patients which was identical to that produced in animals administered lithocholic acid, the 7-alpha-dehydroxylated metabolite of CDCA. the possibility that clinically significant hepatotoxicity could develop with CDCA therapy greater than 24 months thus cannot be excluded by this study.

Adult↗

PubMedDate not supplied

A study of bile canalicular contractions in isolated hepatocytes.

Living hepatocytes observed under standard methods of cell isolation and culture show frequent active contractions of bile canaliculi when viewed by time-lapse cinephotomicrography. This report gives details of the methods used to show the contractions. In addition, the characteristics of the contraction pattern are defined and analyzed. The contractions are regular, canalicular contraction time (systole) lasts 60 sec, and the most probably interval between contractions is 5 1/2 min. The finding of a regular pattern of contraction suggests an ordered, programmed, and integrated mechanism which entails a high degree of communication and functional coordination between neighboring hepatocytes.

Animals↗

PubMedDate not supplied

What is actin doing in the liver cell?

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Actins↗

PubMedDate not supplied

Possible defect in the bile secretory apparatus in arteriohepatic dysplasia (Alagille's syndrome): a review with observations on the ultrastructure of liver.

Ultrastructural observations on 12 liver biopsies from 10 patients with arteriohepatic dysplasia syndrome (Alagille's syndrome) are reported. The electron microscopic changes in the liver in this condition are different from those seen in other forms of chronic intra- and extrahepatic cholestasis. In particular, the bile canalicular and pericanalicular changes classically observed in cholestasis are infrequently seen. When compared with other forms of intrahepatic cholestasis including syndromes associated with paucity of intrahepatic bile ducts, the ultrastructural changes in Alagille's syndrome appear to be distinctive. Bile pigment retention is found in the cytoplasm especially in lysosomes and in vesicles of the outer convex face of the Golgi apparatus (cis-Golgi), but rarely in bile canaliculi or the immediate pericanalicular region. These results suggest a block in the Golgi apparatus or in the pericanalicular cytoplasm.

Bile↗

PubMedDate not supplied

Three-dimensional observations of the hepatic arterial terminations in rat, hamster and human liver by scanning electron microscopy of microvascular casts.

The arterial terminations were studied by scanning electron microscopy of microvascular casts in rat, hamster and human livers. Important species differences were observed. In the rat, frequent anastomoses between the terminal hepatic arterioles and portal venules were observed, whereas a few arterioles terminated directly into sinusoids. On the contrary, no arterioportal venous anastomoses were demonstrated in the hamster and human livers. In these latter species, all arterioles terminated into sinusoids adjacent to the portal tracts. No intralobular arterioles were observed in any species.

Adolescent↗

PubMedDate not supplied

Salvage chemotherapy for relapsed and resistant lymphoma with a carboplatin containing schedule--EPIC.

We have treated 11 patients with relapsed or resistant lymphoma with a combination of Etoposide, Prednisolone, Ifosfamide and Carboplatin (EPIC), obtaining complete responses in two patients and partial responses in four patients for an overall response rate of 54 per cent. The treatment was well tolerated with no toxic deaths and five patients were able to proceed to high dose therapy with autologous bone marrow transplantation (ABMT).

Adolescent↗

PubMedDate not supplied

The present status of xenotransplantation.

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Animals↗