1051
ALUMINIUM HYDROXIDE IN BILE-SALT DIARRHŒA A. SALI
property of antacids in man and, the second, response of bile-salt diarrhoea to treatment with aluminium hydroxide.
bile-acid-binding
to assess
W. R. MURRAY C. MACKAY
Patients and Methods
University Department of Surgery, Western Infirmary, Glasgow G11 6NT The treatment of choleraic diarrhœa remains a problem. Cholestyramine is effective but long-term treatment is often impracticable. In-vitro studies have shown that aluminium hydroxide has bile-acid-binding properties comparable with those of cholestyramine. The bile-acid-binding properties of aluminium hydroxide have now been investigated in vivo and applied to the treatment of patients with choleraic diarrhœa. Aluminium hydroxide increased the fæcal bile-salt concentration of patients with a normal bowel habit whereas magnesium hydroxide had no effect. Eight patients with severe choleraic diarrhœa were treated with aluminium-hydroxide suspension: bowel motion became less frequent and daily fæcal
Summary
weight fell. Introduction THE enterohepatic circulation of bile acids is maintained by active absorption from the terminal ileum, and normally less than 5% of the circulating bile acids enter the colon each cycle.’ If an excess of bile acid enters the colon diarrhoea may result. This symptom, sometimes referred to as choleraic diarrhoea, has been described in Crohn’s disease of the terminal ileum and after ileal resection’ and truncal vagotomy and drainage.2 Patients with choleraic diarrhoea are often significantly incapacitated, both socially and at work, by urgent "explosive"
diarrhoea. The results of diphenoxylate and mebeverine therapy usually disappointing,3 and the most successful treatment for this symptom is the bile-acid-binding resin cholestyramine.4However, cholestyramine is expensive, it takes a long time to prepare, it has an unpleasant taste, and it can cause nausea and vomiting; as a result some patients cannot take the resin long term. In-vitro studies have shown that aluminium hydroxide has bile-acid-binding properties comparable with those of cholestyramine, whereas magnesium hydroxide has a significantly lower bile-acid-binding capacity.’ If these in-vitro results were to be confirmed in vivo this might have significant implications for the treatment of bile-salt diarrhoea. Our aim was, first, to investigate the are
6. Collins, R. L., Turner, R. A., Johnson, A. M., Whitney, N. O., McLean, R. L. Arthritis Rheum. 1976, 19, 623. 7. Sjöblom, K. A., Wollheim, F. A. Lancet, 1977, ii, 41. 8 Walker, W. C. Q. Jl Med. 1967, 36, 239. 9. Ritchie, R. F., Alper, C. A., Grave, J., Pearson, N., Larson, C. Am. J. clin. Path. 1973, 59, 151. 10. Arnaud, P., Chapuis-Cellier, C., Creyssel, R. Protides biol. Fluids, 1975, 22, 515. 11. Lebas, J., Hayem, A., Martin, J. P. C. R. Acad. Sci. Paris, 1974, 278, 2359. 12. Fagerhol, M. K. Protides biol. Fluids, 1975, 22, 493. 13. Ward, A. M., Pickering, J. D., Fagerhol, M. K., Martin, J. P. Hum. Here-
dity, 1977, 27, 292. 14. Stastny, P. J. clin. Invest. 1976, 57, 1148. 15. Stastny, P., Sittler, S., Fink, C. W. Tissue Antigens, 1977, 10, 210. 16. Evans, C. C., Evans, J. M. Lancet, 1975, ii, 975. 17. Frank, S. T., Weg, J. G., Harkelroad, L. E. Chest,
1973, 63, 27.
Study1 Nine male patients taking antacids for symptoms of peptic ulceration were investigated. Duodenal ulceration had been confirmed by barium meal or endoscopy. Aluminium hydroxide (’Aludrox’) or magnesium hydroxide (’Milk of Magnesia’) was given orally for 6 days. Fxces were collected over the last 2 days of treatment. At the end of the 6-day period patients were switched from one antacid to the other and the 2-day faecal collections were repeated. The antacid given first to each patient was randomly selected. The dosage of aluminium hydroxide was 15 ml four times a day. The dosage of magnesium hydroxide used was 10 ml four times a day because higher doses caused diarrhoea in some patients. Eleven age-matched controls, men who were free from gastrointestinal disease and were taking no drugs, were also studied. The mean age of the duodenal-ulcer group was 46 and the mean age of the controls was 47. Faeces were collected over a 2-day period from the controls. Patients and controls were advised to continue with their normal outpatient diet. Only patients and controls with a regular daily bowel habit were included, to facilitate accurate estimations of daily faecal bile-salt concentrations. Faecal bile salts were extracted by a modification of the techniques described by Hill and Aries.6 Bile-salt concentrations were measured with the 3&agr;-hydroxysteroid-dehydrogenase method.’ This technique permitted estimation of faecal bile-salt concentration from a freeze-dried sample of fw-ces, and bile-salt output was then calculated from the daily faecal weight.
Study 2
Eight patients with severe choleraic diarrhoea were investigated. Six had had an ileal resection for Crohn’s disease of the terminal ileum and two had had diarrhoea continuously since a truncal vagotomy and pyloroplasty for chronic duodenal ulceration. All these operations had been done at least 3 years previously, and the eight patients were passing at least five watery unformed urgent stools per day. Dietary treatment and diphenoxylate, mebeverine, and pancreatic extract had been tried with poor response. Four patients had been treated with cholestyramine with satisfactory control of the diarrhoea, but they could not tolerate the resin over a long period. Eight age and sex matched patients who were free from gastrointestinal disease were used as controls. 2-day faecal collections were taken from all sixteen patients and fsecal bile-salt concentration and output were estimated. The eight patients with choleraic diarrhoea were then given aludrox 40-120 ml per day, depending on the response. Aludrox was usually administered two or three times a day. The patients were interviewed twice weekly and asked to record the frequency of their bowel motions. Blood was taken for full blood count, urea, electrolytes, and liver-function tests before and during treatment with aluminium hydroxide. Faecal bilesalt concentrations and daily outputs were again estimated once a significant improvement had been observed in their diarrhoea.
Results
Study 1 Bile-salt concentrations were significantly higher in patients taking aluminium hydroxide than in controls (mean + S.E.M. 23.55 and 14 µmol/g, respectively but concentrations in patients receiving (P
ALUMINIUM HYDROXIDE IN BILE-SALT DIARRHŒA A. SALI
property of antacids in man and, the second, response of bile-salt diarrhoea to treatment with aluminium hydroxide.
bile-acid-binding
to assess
W. R. MURRAY C. MACKAY
Patients and Methods
University Department of Surgery, Western Infirmary, Glasgow G11 6NT The treatment of choleraic diarrhœa remains a problem. Cholestyramine is effective but long-term treatment is often impracticable. In-vitro studies have shown that aluminium hydroxide has bile-acid-binding properties comparable with those of cholestyramine. The bile-acid-binding properties of aluminium hydroxide have now been investigated in vivo and applied to the treatment of patients with choleraic diarrhœa. Aluminium hydroxide increased the fæcal bile-salt concentration of patients with a normal bowel habit whereas magnesium hydroxide had no effect. Eight patients with severe choleraic diarrhœa were treated with aluminium-hydroxide suspension: bowel motion became less frequent and daily fæcal
Summary
weight fell. Introduction THE enterohepatic circulation of bile acids is maintained by active absorption from the terminal ileum, and normally less than 5% of the circulating bile acids enter the colon each cycle.’ If an excess of bile acid enters the colon diarrhoea may result. This symptom, sometimes referred to as choleraic diarrhoea, has been described in Crohn’s disease of the terminal ileum and after ileal resection’ and truncal vagotomy and drainage.2 Patients with choleraic diarrhoea are often significantly incapacitated, both socially and at work, by urgent "explosive"
diarrhoea. The results of diphenoxylate and mebeverine therapy usually disappointing,3 and the most successful treatment for this symptom is the bile-acid-binding resin cholestyramine.4However, cholestyramine is expensive, it takes a long time to prepare, it has an unpleasant taste, and it can cause nausea and vomiting; as a result some patients cannot take the resin long term. In-vitro studies have shown that aluminium hydroxide has bile-acid-binding properties comparable with those of cholestyramine, whereas magnesium hydroxide has a significantly lower bile-acid-binding capacity.’ If these in-vitro results were to be confirmed in vivo this might have significant implications for the treatment of bile-salt diarrhoea. Our aim was, first, to investigate the are
6. Collins, R. L., Turner, R. A., Johnson, A. M., Whitney, N. O., McLean, R. L. Arthritis Rheum. 1976, 19, 623. 7. Sjöblom, K. A., Wollheim, F. A. Lancet, 1977, ii, 41. 8 Walker, W. C. Q. Jl Med. 1967, 36, 239. 9. Ritchie, R. F., Alper, C. A., Grave, J., Pearson, N., Larson, C. Am. J. clin. Path. 1973, 59, 151. 10. Arnaud, P., Chapuis-Cellier, C., Creyssel, R. Protides biol. Fluids, 1975, 22, 515. 11. Lebas, J., Hayem, A., Martin, J. P. C. R. Acad. Sci. Paris, 1974, 278, 2359. 12. Fagerhol, M. K. Protides biol. Fluids, 1975, 22, 493. 13. Ward, A. M., Pickering, J. D., Fagerhol, M. K., Martin, J. P. Hum. Here-
dity, 1977, 27, 292. 14. Stastny, P. J. clin. Invest. 1976, 57, 1148. 15. Stastny, P., Sittler, S., Fink, C. W. Tissue Antigens, 1977, 10, 210. 16. Evans, C. C., Evans, J. M. Lancet, 1975, ii, 975. 17. Frank, S. T., Weg, J. G., Harkelroad, L. E. Chest,
1973, 63, 27.
Study1 Nine male patients taking antacids for symptoms of peptic ulceration were investigated. Duodenal ulceration had been confirmed by barium meal or endoscopy. Aluminium hydroxide (’Aludrox’) or magnesium hydroxide (’Milk of Magnesia’) was given orally for 6 days. Fxces were collected over the last 2 days of treatment. At the end of the 6-day period patients were switched from one antacid to the other and the 2-day faecal collections were repeated. The antacid given first to each patient was randomly selected. The dosage of aluminium hydroxide was 15 ml four times a day. The dosage of magnesium hydroxide used was 10 ml four times a day because higher doses caused diarrhoea in some patients. Eleven age-matched controls, men who were free from gastrointestinal disease and were taking no drugs, were also studied. The mean age of the duodenal-ulcer group was 46 and the mean age of the controls was 47. Faeces were collected over a 2-day period from the controls. Patients and controls were advised to continue with their normal outpatient diet. Only patients and controls with a regular daily bowel habit were included, to facilitate accurate estimations of daily faecal bile-salt concentrations. Faecal bile salts were extracted by a modification of the techniques described by Hill and Aries.6 Bile-salt concentrations were measured with the 3&agr;-hydroxysteroid-dehydrogenase method.’ This technique permitted estimation of faecal bile-salt concentration from a freeze-dried sample of fw-ces, and bile-salt output was then calculated from the daily faecal weight.
Study 2
Eight patients with severe choleraic diarrhoea were investigated. Six had had an ileal resection for Crohn’s disease of the terminal ileum and two had had diarrhoea continuously since a truncal vagotomy and pyloroplasty for chronic duodenal ulceration. All these operations had been done at least 3 years previously, and the eight patients were passing at least five watery unformed urgent stools per day. Dietary treatment and diphenoxylate, mebeverine, and pancreatic extract had been tried with poor response. Four patients had been treated with cholestyramine with satisfactory control of the diarrhoea, but they could not tolerate the resin over a long period. Eight age and sex matched patients who were free from gastrointestinal disease were used as controls. 2-day faecal collections were taken from all sixteen patients and fsecal bile-salt concentration and output were estimated. The eight patients with choleraic diarrhoea were then given aludrox 40-120 ml per day, depending on the response. Aludrox was usually administered two or three times a day. The patients were interviewed twice weekly and asked to record the frequency of their bowel motions. Blood was taken for full blood count, urea, electrolytes, and liver-function tests before and during treatment with aluminium hydroxide. Faecal bilesalt concentrations and daily outputs were again estimated once a significant improvement had been observed in their diarrhoea.
Results
Study 1 Bile-salt concentrations were significantly higher in patients taking aluminium hydroxide than in controls (mean + S.E.M. 23.55 and 14 µmol/g, respectively but concentrations in patients receiving (P
