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Biomedical subjects

E Krag

Publications and source records attributed to E Krag.

At least 37 records · Page 2Linked to original sources

The effect of i.v. indomethacin on the gastric mucosal electrical potential difference and blood flow in anaesthetized dogs.

Indomethacin inhibits prostaglandin synthesis and causes gastric mucosal damage. The correlation between the gastric mucosal function and gastric blood flow was investigated. The intragastric liquid junction corrected potential difference (PD) across the stomach wall was used to characterize the gastric mucosal function. Mucosal blood flow was determined by the radiolabelled microsphere technique. Seven dogs were anaesthetized, intragastric PD was measured continuously and blood flow determined at basal condition during sympathetic activation, and after IV indomethacin (7.5 mg/kg). PD was unchanged during the basal period and during mild sympathetic activation. After indomethacin PD was reduced significantly (-40 +/- 6 mV to -20 +/- 5 mV, measured with gastric lumen negative, mean and SD, P less than 0.05). Mucosal blood flow decreased during sympathetic activation and a further significant reduction was seen after indomethacin. PD and flow reductions correlated (R = 0.92). As indomethacin given IV caused a parallel impairment of gastric mucosal function and blood flow, part of the indomethacin-related mucosal damaging effects might be due to the flow reduction.

Animals

The influence of ispaghula husk and lactulose on the in vivo and the in vitro production capacity of short-chain fatty acids in humans.

To evaluate factors influencing the short-chain fatty acid (SCFA) concentrations in stools, three different experiments were performed: faecal concentrations of SCFA at defecation were determined by gas liquid chromatography in nine healthy volunteers on a free diet. SCFAs were 114 +/- 15.0 mmol/l (means +/- SD). The coefficient of variation (CV) of the assay was 4-15%, the intraindividual CV 12-33%, and the interindividual CV 11-29%. On incubation of faeces at 37 degrees C concentrations of SCFA doubled in 6 h and rose fourfold in 72 h. In three volunteers the experiments were extended by adding ispaghula husk or lactulose to the diet for two 14-day periods each; no change in faecal SCFA concentrations was seen, either at defecation or after incubation. When ispaghula husk or lactulose was added to faeces in an in vitro incubation system, the concentrations of SCFA were five times higher than those of controls. We conclude that instant handling of faeces is essential for determinations of SCFA concentrations to obtain interpretable and comparable results; that determination of total SCFA output is of limited value; that addition of fibre to the diet does not influence faecal SCFA concentrations; and that the capacity for SCFA production in faeces is large provided a sufficient amount of substrate is available.

Adult

Short-chain fatty acids and the irritable bowel syndrome: the effect of wheat bran.

Short-chain fatty acids (SCFA) in faeces were examined in 18 patients with the irritable bowel syndrome (IBS) during treatment with wheat bran or placebo. In the placebo period, the patients could be classified in accordance with the faecal concentrations of SCFA into one group with low concentrations (mean, 40 mmol/l; range, 19-77 mmol/l; 10 patients) and another with high concentrations (mean, 168 mmol/l; range, 145-187 mmol/l; 8 patients). The concentrations of SCFA differed (P less than 0.001) in both groups from concentrations found in faeces from a reference group of nine normal individuals (mean, 114 mmol/l; range, 93-155 mmol/l). Patients with low levels of SCFA had lower (P less than 0.001) mean stool mass and longer (P less than 0.05) transit times than those with high concentrations of SCFA in faeces. Ingestion of bran, although a precursor of SCFA, did not change faecal concentrations of SCFA. Abdominal pain, distension, and rumbling were not correlated to low or high concentrations of SCFA in faeces, nor did bran improve these symptoms when compared to placebo. The level of SCFA was rather constant intraindividually and independent of the variability of the daily faecal mass. It is concluded that patients with IBS apparently have continuously abnormal concentrations of SCFA in faeces, either high or low, which are unaffected by the treatment with bran and which hypothetically may be of pathophysiologic importance.

Adult

A new method for measurement of the electrical potential difference across the stomach wall. Clinical evaluation of the gastric mucosal integrity.

PD, the electrical potential difference across the gastric mucosa, is a variable used frequently in experimental studies. Existing methods for PD measurements are, however, unstable, and variations in the pH of the gastric juice causes liquid junction potentials between gastric juice and the PD measuring probe. A new PD measuring system has been developed with high stability, easy handling, and correction for the liquid junction potentials. PD was measured between a stomach microelectrode and an intravenous reference electrode connected to a millivoltmeter. pH was measured by an intragastric microelectrode. The liquid junction potential was calculated by using the pH measured in the gastric juice and the Henderson equation and was then subtracted from the measured PD to provide a better approximation of the PD across the mucosa. The liquid junction potential calculated as stated above correlated with the liquid junction potential calculated from precise ion determinations made in gastric juice samples (y = x; r = 0.92; p less than 0.05). The reliability of the PD measuring system was tested in vitro and in vivo and was satisfactory. In conclusion, a new, reliable, and easily applied method for gastric PD measurements corrected for the liquid junction potential between gastric juice and the PD measuring probe has been developed.

Action Potentials

Effect of enterocoated cholestyramine on bowel habit after ileal resection: a double blind crossover study.

Ileal resection causes malabsorption of bile acid; the increased load of bile acids in the colon induces increased secretion of salt and water and hence diarrhoea. A study was carried out to test the effect of an enterocoated cholestyramine tablet designed to disintegrate in the colon and sequester the bile acids there, thereby minimising diarrhoea induced by bile acids while having no effect on malabsorption of bile acid and jejunal fat absorption. The study comprised 14 patients who had undergone ileal resection of 40-150 cm for Crohn's disease. A double blind crossover trial was performed with placebo and cholestyramine enterocoated with cellulose acetate phthalate. During treatment with cholestyramine the daily faecal output decreased, the number of defecations each week decreased, and the intestinal transit time increased. Acceptability of the tablets was high, in contrast with general clinical experience with cholestyramine powder. No change was observed in the total faecal output of bile acids or fat. Cholestyramine tablets caused a reduction in diarrhoea without noticeably interfering with the metabolism of fat or bile acid.

Adult

The effect of coarse wheat bran in the irritable bowel syndrome. A double-blind cross-over study.

Dietary supplementation with wheat bran has been widely advocated as a first-line treatment of patients with the irritable bowel syndrome (IBS). Few controlled trials have been reported, and the results are, furthermore, contradictory. The present study comprised 20 patients with IBS, of whom 18 (14 women, 4 men) completed the trial. The two treatment periods of 6 weeks each, with a daily intake of 30 g coarse wheat bran or 30 g placebo bran, respectively, were randomized in a double-blind cross-over design. Wheat bran significantly (P less than 0.05) increased the stool weight and shortened the intestinal transit time but was without significant effect on the colonic motility index was shown. We conclude that coarse wheat bran used as the only treatment in IBS does not provide a sufficient effect in a 6-week period. However, wheat bran seems to be justified in the treatment of constipation.

Adult

Irritable bowel syndrome: current concepts and future trends.

About five per cent of the adult population each year will see their doctor with complaints that are finally characterised as irritable bowel syndrome (IBS). The complaints are constipation (perhaps alternating with diarrhoea), abdominal pain (dull or colicky), abdominal distension, abdominal rumbling and flatulence. The diagnosis of IBS implies that a relevant examination has precluded any organic disease. The etiology is unknown and the syndrome probably does not represent a disease entity. It is therefore difficult, if not impossible, to produce a definite rationale of treatment. However, several aspects of the pathogenesis of the individual symptoms of IBS are well known: 1) chronic constipation is most likely due to fibre-depleted diet, psychological factors, local organic disorders (e.g., anal fissures, hemorrhoids, diverticulosis) and disturbance of the body fluid balance (e.g., high consumption of diuretic compounds such as coffee and tea); 2) pain is related to spasms and motility disturbances causing increased intraluminal pressure; 3) meteorism is not due to an increased amount of intestinal gas, but "air traps" and segmental accumulation of gas seem to occur. Furthermore, psychopathological factors and perhaps also food intolerance may play an etiological role. At present the rationale of treatment in IBS is: 1) management of constipation, 2) ease of spasms, 3) reduction of surface tension of intestinal contents, 4) ease of mental stress.

Abdomen

A computer model simulating the intestinal absorption of bile acids.

Mathematical models were developed for assessment of the absorption kinetics of compounds passing down the length of a perfused intestinal segment. The models considered the intestinal segment as a cylinder composed of a large number of very small (infinitesimal) cylinders and described the concentration decline of the compound in situations with active, passive and combined active and passive transport. The maximal velocity of active transport, Vmax, the Michaëlis-Menten constant, Km, and the permeability coefficient, P, were calculated. A computer program was developed to operate the mathematical expressions. The models were validated by jejunal and ileal perfusions of various bile acids in six healthy volunteers. The fit between the mathematical models and the actually measured data showed an average standard deviation of 0.14 mmol/l (substrate infusion concentration ranging from 0.25 mmol/l to 3.0 mmol/l). It was concluded that the computer models were feasible for practical purposes. Moreover, the models reduced the number of perfusions necessary to determine the absorption kinetics of a given bile acid.

Adult

Spontaneous healing of duodenal ulcers.

Ninety-one patients with duodenal, pyloric, or prepyloric ulcers were studied endoscopically. Spontaneous ulcer healing was seen in 29 patients within 2 weeks (rapid healing) and in 23 patients within 6 weeks (slow healing). More ulcers healed spontaneously in women than in men (P less than 0.05). Spontaneous healing in men was related to a low gastric peak acid output (P less than 0.05). During follow-up study for 2 years of patients with spontaneously healed ulcers 13 patients had no recurrence, whereas 19 patients had 1 or 2 recurrences, which also healed spontaneously; 11 patients had to be given active treatment, and 9 patients did not complete the study. Cigarette smoking was more frequently recorded in the group receiving active treatment than in the group with spontaneous healing. In men ulcers needing active treatment during the follow-up period were related to a high peak acid output (P less than 0.05).

Adult

Effect of oat bran on lithogenic index of bile and bile acid metabolism.

Epidemiological studies lend support to the hypothesis that high-fibre diets might prevent and low-fibre diets might facilitate the formation of cholesterol gall stones. In the present study, the bile compositions after ingestion of oat bran 18 g/day and placebo 18 g/day for 2 X 2 weeks were compared in a randomized, double-blind cross-over study in 6 healthy volunteers. The lithogenic index of bile was not influenced, whereas the following changes (0.05 less than p less than 0.10) occurred: the cholic acid pool was enlarged, the relative proportion of chenodeoxycholate in bile was increased and that of deoxycholate reduced, while cholate remained unchanged. It is concluded that oat bran seems to influence the metabolism of bile acids.

Adult

Mucosal function of the perfused ileum in patients with and without diarrhoea and dumping after vagotomy and pyloroplasty.

Perfusion studies of the terminal ileum were performed in patients who had previously had vagotomy and pyloroplasty performed for peptic ulcer disease and who at follow-up study had either diarrhoea or dumping, or no symptoms (the control group). The aim was to elucidate possible pathophysiological factors contributing to the sequelae. Net movements of water, electrolytes, and sugars, unidirectional fluxes of sodium and chloride, and the transmural electrical potential difference (PD) were measured simultaneously with and without the influence of chenodeoxycholic acid (CDC), 1.0 mmol/l, in the intestinal lumen. In patients without symptoms or with dumping, water and sodium chloride were absorbed during the control perfusion. Addition of CDC reduced the absorption or evoked secretion. In patients with diarrhoea the control perfusion disclosed a large spontaneous ileal secretion that was not influenced by CDC. The secretion was mainly due to a reduced mucosa-to-serosa flux of sodium and chloride and, to a lesser extent, to an increased serosa-to-mucosa flux. The diarrhoea patients showed an increased xylose absorption rate, suggesting an increased interepithelial leakiness. No change in PD was demonstrated. The effect of CDC on the unidirectional fluxes was identical in all three groups of patients. In conclusion, our findings suggest that the basic biological mechanisms are identical (and normal) in all patients, but the ileal epithelium of patients with diarrhoea secretes spontaneously and seems to be prestimulated by some at present unidentified agent.

Adult

Enzymatic determination of total 3 alpha-hydroxy bile acids in faeces. Validation in healthy subjects of a rapid method suitable for clinical routine purpose.

A method for determining faecal bile acids, suitable for clinical purposes, is introduced. The analysis uses a 0.2-g stool specimen, a simple extraction procedure, and 3 alpha-steroid dehydrogenase determination. The method, which is rapid, has been validated by gas-liquid chromatography and by recovery of internal standards. Stool examination was done in 16 healthy volunteers on free diet and in 25 patients with non-gastrointestinal diseases who were on a fat- and fibre-fixed diet. No difference was found between the two groups, so the data were pooled, and the normal reference interval (mean +/- S.D.) for faecal bile acid output was calculated to be 0-975 mumol/24h.

3-Hydroxysteroid Dehydrogenases