A. M. Dawson

Effects of lactulose and other laxatives on ileal and colonic pH as measured by a radiotelemetry device

Using a pH-sensitive radiotelemetering device the effect of lactulose on luminal pH in the ileum, colon, and rectum has been compared with that of two other laxative agents. Lactulose produced marked acidification of proximal colonic contents but this effect was not consistently maintained into the distal colon. Sodium sulphate acidified distal rather than proximal colonic contents. However, for a similar degree of laxation it was not possible to produce a significantly more uniform reduction of pH along the length of the colon by combining these laxatives compared with lactulose alone. Magnesium sulphate had little effect upon luminal pH except in the rectum where a significant rise occurred. These results are discussed in relation to both normal colonic physiology and to their possible relevance to the treatment of chronic hepatic encephalopathy by colonic acidification.

Is bran efficacious in irritable bowel syndrome? A double blind placebo controlled crossover study.

Twenty eight patients with classical irritable bowel syndrome completed a double blind placebo controlled crossover trial in which they added to their normal diet a daily supplement of either 12 bran biscuits (1 = 1.3 g fibre) or 12 placebo biscuits (1 = 0.23 g fibre). Each biscuit was given for three months in random order with crossover to the alternative biscuit at three months. After the initial three months therapy, there was a significant symptomatic improvement compared with pretreatment in both the bran treated (p less than 0.01) and placebo treated groups (p less than 0.01), but there was no significant difference in symptom scores between these two groups. There was no further improvement in either group after the second three months treatment with the alternative therapy. When crossover data for all 28 subjects were combined, symptoms scores after three months bran therapy and after three months placebo therapy did not differ significantly. Twenty four patients completed three day stool collections in both treatment periods. When the symptomatic response to bran among 15 subjects in whom stool weights rose on bran was compared with that among nine subjects whose stool weights were static or fell on the bran, it was shown that symptomatic improvement was independent of an increase in stool weight. These data suggest that in irritable bowel syndrome, especially that associated with abdominal pain, the beneficial effects of bran are due to a placebo response which is independent of an increase in stool weight.

Experience with Coeliac Axis Compression Syndrome

Seven patients with “coeliac axis compression syndrome” are reported. Five were treated surgically, but only two did well. A survey of 200 healthy adults showed epigastric bruits in 6·5%; only one of these had dyspepsia, though dyspepsia was present in 12·5% overall. Caution is urged in attributing a causal relationship between coeliac axis compression and pain and in proceeding to arteriography when compression is suspected on clinical grounds.

Functional differentiation of human jejunum and ileum: A comparison of the handling of glucose, peptides, and amino acids

The characteristics of glucose, glycine, L-alanine, and glycyl-L-alanine absorption from the jejunum and ileum have been compared in normal human subjects. A perfusion technique has been used, and correct positioning of the perfusion tube has been confirmed by measuring the differential jejunal and ileal handling of bicarbonate. Glucose and glycine were absorbed faster from the jejunum than from the ileum of all subjects studied, and L-alanine was absorbed faster from the jejunum than from the ileum in five out of six subjects studied. In contrast, the dipeptide glycyl-L-alanine was absorbed at comparable rates from the jejunum and ileum. Higher concentrations of free amino acids were detected in the luminal contents aspirated during the ileal dipeptide perfusions. These results emphasize the importance of oligopeptide transport in the absorption of protein digestion products, especially in the human ileum, and the practical implications of these findings are discussed.

Relationship between gastric acid and elevated plasma somatostatinlike immunoreactivity after a mixed meal

The aim of this study was to examine whether hydrochloric acid plays a role mediating the post-prandial increase in plasma somatostatinlike immunoreactivity in normal subjects. Intravenous infusion of cimetidine was found to reduce by 45% the postprandial increment in plasma somatostatin-like immunoreactivity. This effect was reversed by concomitant intragastric administration of 0.1 N hydrochloric acid, which in previous studies in fasted subjects had not affected plasma somatostatinlike immunoreactivity. The effects of cimetidine on postprandial plasma gastrin were the inverse of those observed on postprandial somatostatin. There was a greatly enhanced increment in postprandial plasma gastrin during cimetidine infusion, which was reduced significantly toward control levels by concomitant intragastric infusion of hydrochloric acid. To exclude direct inhibition by cimetidine of nutrient-stimulated plasma somatostatinlike immunoreactivity we studied the effect of cimetidine on plasma somatostatinlike immunoreactivity stimulated by an intraduodenal infusion of fat. Cimetidine did not alter the incremental response of somatostatinlike immunoreactivity to intraduodenal fat infusion. These data show that cimetidine does not invariably reduce nutrient-stimulated plasma somatostatinlike immunoreactivity and are consistent with the hypothesis that the action of cimetidine in reducing the plasma somatostatin response to ingestion of a meal is a consequence of reduction of postprandial acid secretion. These data suggest that the postprandial elevation in plasma somatostatin observed in humans is mediated in part through postprandial secretion of gastric acid, which in turn acts to elevate plasma somatostatin.

Limitation of the use of inert gases in the measurement of small gut mucosal blood flow.

The role of blood flow in absorption from the small gut would be best studied by a method able to measure exclusively blood flow in the small gut mucosa because this might vary independently of total small gut blood flow. Such a method should be repeatable to give values in control and experimental periods, and one would hope that it would be adaptable for use in man. We had hoped to meet these criteria by measuring the rate of removal of 133Xenon from fluid in the lumen of the small gut. Kety (1951) has described the factors involved in the use of inert gases to measure tissue blood flow. In muscle (e.g., Lassen, H0edt-Rasmussen, Lindjberg, Pedersen, and Munck, 1963), myocardium (e.g., Ross, Ueda, Lichtlen, and Rees, 1964), and brain (e.g., Lassen and Klee, 1956) blood flow has been measured from the rate of disappearance of radioactive inert gases out of the tissue. The validity of these methods depends upon the assumption that diffusion of gas through the tissue is so fast that it does not delay its removal, which is therefore dependent only upon blood flow. In the gut, if the same assumption holds true, then when the gas is dissolved in fluid placed in the gut lumen, the rate of its removal will be proportional to blood flow in the mucosa, and will be unaffected by blood flow in any other part of the gut wall.

A physicochemical study of fat absorption in rats. Limitation of methods in vitro.

Abstract 1. 1. The hypothesis that the first stage of normal fatty acid absorption represents a partition between a luminal bile salt mixed micellar phase and mucosal membrane lipid phase has been investigated. 2. 2. Everted segments of rat jejunum incubated with [14C]oleic acid in 10 mM sodium taurocholate accumulated a greater amount of 14C-labelled free fatty acid when incubated at pH 5.8 then at pH 7.3 but this was unrelated to incorporation into jejunal [14C]triglyceride. 3. 3. Uptake of [14C]oleic acid into mucosal free fatty acid from 15 mM taurocholate (20 μmoles/ml) in vitro was less than from 6 mM taurocholate, but the triglyceride accumulation was greater. 4. 4. pH had no effect on the uptake in vitro of the non-ionized oleyl alcohol from taurocholate mixed micellar solution but with increasing taurocholate concentration there was decreased uptake of [14C] oleyl alcohol. 5. 5. Increasing concentrations of [14C]oleic acid in bile salt mixed micelles caused an increase both of 14C-labelled free fatty acid and [14C]triglyceride in vitro. 6. 6. Absorption of [14C]oleic acid from perfused or closed loops of jejunum in vivo was increased with increased oleic acid concentration but was not influenced by pH or bile salt concentration. 7. 7. These findings suggest that although uptake of free fatty acid by the mucosal cell in vitro may be predicted on the basis of a partition between micelle and lipid membrane via a molecular phase, this is not an important mechanism during normal fatty acid absorption.

The absorption of tristearin and stearic acid and tripalmitin and palmitic acid: Studies on the rate-limiting steps in rats

Abstract 1. 1. In free feeding experiments in rats the absorption of labelled tristearin was poor. It remained constant over a wide dose range, but fell with a high dose. The absorption in bile fistula rats was diminished. 2. 2. The addition of triolein increased the absorption of labelled tristearin in control rats but not in bile fistula rats, suggesting that poor solubility in bile salt solution is an important step hindering the absorption of tristearin and that triolein stimulates absorption by increasing this solubility. 3. 3. Jejunal segments incubated in a micellar solution of equal concentration of labelled stearic acid and oleic acid in 10 mM sodium taurocholate took up stearic acid at a slightly faster rate than oleic in a ratio of 0.84, but incorporation into triglyceride was greater for oleic acid in the ratio of 1.3. 4. 4. When a micellar solution of equal concentration of labelled oleic and stearic acids were infused into the duodenum the content of oleic acid in lymph triglyceride was greater than that of stearic acid in a ratio of 1.35. 5. 5. When equal weights of labelled oleic and stearic acids were fed, mixed with bran, the content of oleic acid in lymph triglyceride was much greater than that for stearic acid, in a ratio of 8.9 in the first hour, falling to 4.5 by the fourth hour. These ratios are much greater than those during lymphatic absorption from equimolar micellar solution. 6. 6. We conclude that micellar solubilisation is a major rate-limiting step in the absorption of tristearin and stearic acid, that mucosal cell uptake is not rate-limiting and that esterification is only a minor rate-determining step. 7. 7. The absorption of palmitic acid by control rats was slightly increased by a large dose of triolein added to the feed, but that of tripelmitin was unaltered. Reasons for the difference in behaviour between tripalmitin and tristearin are discussed.

Oleic Acid Absorption from Micellar Solutions and Emulsions in the Rat

Summary Closed loops of rat jejunum in vivo have been used to study the absorption of oleic acid from nonmicellar and micellar taurocholate solutions and compared with that from micellar solutions of a nonionic detergent Pluronic Acid F 68. (a) Absorption from 15 mM taurocholate was greater than from 1 mM taurocholate over a range of oleic acid concentrations. (b). Absorption of oleic acid was proportional to its total and not its micellar concentration. (c) Pluronic acid micelles were as efficient as taurocholate micelles in promoting absorption from a 10 mM oleic acid solution but had no advantage over a nonmicellar solution at low oleic acid concentration 0.1 mM.