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Introduction:The cathartic effect of bile has been known for some years (Labotke 1937) and bile acids have been recognized as being capable of inducing colonic evacuation (Galapeaux, Tepleton &Borkon 1938). In the last two decades enormous numbers of studies have been conducted on the pathophysiology of bile acids, mainly because of their importance in lipid solubilization and also because of their efficacy in dissolving cholesterol gallstones. However, several effects on intestinal physiology have been also identified. Particularly, Mekhjian et al demonstrated, in human perfusion studies, that dihydroxy bile acids promote colonic secretion of water and electrolytes (Mekhjian, Philips & Hofmann 1971). In some patients with ileal resection, diarrhoea is probably induced by bile acid malabsorption since the administration of cholestyramine, a bile acid-binding resin, reduces the frequency of bowel movements(Hofmann & Roley 1972).

Furthermore, Hepner and Hofmann (1973)demonstrated, in a controlled study, that cholic acid causes a significant increase of faecal frequency in patients with chronic constipation. These authors elected to test cholic acid, in the treatment of constipation, 'because its majordegradation product, deoxycholic acid, has the greatest secretory effect of the bile acids present in man'. Chenodeoxycholic acid, the primary dihydroxy bile acid, has been shown to be effective in dissolving cholesterol gall-stones (Danzinger, Hofmann & Schoenfield 1972, Fromm, Escheer & Tollner 1975, Schoenfield et a11981, Roda et aI1982). Diarrhoea, however, has been indicated as a potential side-effect during the chronic administration of the cholelitholytic bile acid (Danzinger et al 1972, Fromm et al 1975,Schoenfield et a11981, Roda et al 1982). The aim of the present study was to investigate whether the cathartic effect of chenodeoxycholic acid, well documented during cholelitholytic treatment, could be helpful in the management of patients with chronic constipation.To test this hypothesis we performed a blind controlled study comparing chenodeoxycholic acid with placebo in twenty patients with constipation.

Experimental Design
Twenty cholesterol gall-stone patients (sixteen females and four males, mean age 44 years, range 30-65; mean % ideal weight 106, range 91-133) referred to our Unit for cholelitholytic treatment, were admitted to the study. All patients had histories of 2 years or more of constipation, with two or less hard bowel motions per week. The twenty patients were randomly treated with either chenodeoxycholic acid 750 mg/day (about 10mg/kg/day) or placebo, for a period of4 weeks.

Chenodeoxycholic acid was provided by the Gipharmex Company (Milan, Italy) and was proved to be 98% pure, as assessed by gas liquid and thin layer chromatography. Both chenodeoxycholic acid and the placebo were administered daily in three divided doses with meals. A card was given to each patient and they were instructed to record both the frequency and the consistency of their stools(hard,formed,mushy or liquid). The cards were checked weekly by one of the investigators who was not aware of the patients’ treatment.

 

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