Biomedical subjects
E Krag
Publications and source records attributed to E Krag.
Tea consumption: a cause of constipation?
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Secretion rate of intestinal immunoglobulins, complement factor C3, "acute phase" reactants, and albumin in the perfused ileum and jejunum of normal man.
A new method for assessment of the intestinal secretion rate of immunoglobulins and other proteins is evaluated. The procedure involves a combination of luminal perfusion of a defined intestinal segment and analysis of the aspirated perfusates by rocket immunoelectrophoresis. The technique is sensitive and reliable. A material from the normal human jejunum and ileum is presented. The method is proposed as an investigative tool for characterization of the local immunological system of the small intestine.
Bile acid metabolism after intestinal bypass operations.
Intestinal bypass operation for obesity results in substantial weight loss only if the small bowel segment left in function is 50 cm or less. The anatomical changes induce interruption of the enterohepatic circulation of bile acids, which result in bile acid malabsorption. This review discusses the various aspects of the disturbed bile acid metabolism. A small number of controlled prospective studies have focused on the problems of the jejunoileal ratio (JIR) of the functioning segment in relation to the changes induced on the bile acid metabolism. 1:3 JIR results in a significantly: (1) lower bile acid pool size; (2) lower postprandial concentration of bile acid in the jejunum: (3) lower ratio of glycine to taurine conjugates; (4) higher cholesterol saturation index in bile, compared to 3:1 JIR. Thus, the studies mentioned have not only elucidated the changes in bile acid metabolism after jejunoileostomy, but also given support to a new hypothesis that a functioning upper jejunum is necessary for the bile acid synthesis as such. This hypothesis is further supported by the finding that 1:3 JIR at follow-up has a three fold higher rate of gallstones than 3:1 JIR (p less than 0.05).
[Effect of oat brain on intestinal transit time, feces volume and excretion of fecal bile acids in healthy volunteers. A controlled double-blind study].
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[Cellulose acetate phthalate coating of tablets disintegrating at a predetermined intestinal position].
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Prophylactic effect of cimetidine in duodenal ulcer disease.
Fifty-seven symptom-free patients with duodenal ulcer entered a double-blind trial to assess the prophylactic effect of cimetidine. Patients were randomly allocated to receive cimetidine 400 mg twice daily (29 patients) or placebo (28 patients). The trial was designed to imitate daily clinical practice, so duodenal ulcer disease was diagnosed by means of x-ray examination. Three patients from each group withdrew from the trial. All remaining patients continued to receive treatment for 12 months or until symptoms recurred. Three out of 26 patients suffered relapses during cimetidine treatment, compared with 20 out of 25 receiving placebo. No side effects were attributable to cimetidine. Long-term cimetidine treatment had no curative effect as relapses occurred soon after treatment was stopped. The estimated chance (cumulative remission rate +/- 2 SE) of remaining symptom-free 13 weeks after one year's cimetidine treatment had been completed was 47 +/- 21%. Maintenance treatment with cimetidine is a suitable alternative to elective in surgery in patients with duodenal ulcer subjects frequent relapses. Further study is needed to establish the optimal duration and safety of prolonged cimetidine treatment.
[Cimetidine treatment of Ménétrier's syndrome].
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A secretory epithelium of the small intestine with increased sensitivity to bile acids in irritable bowel syndrome associated with diarrhoea.
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Cimetidine treatment of protein-losing gastropathy (Ménétrier's disease). A clinical and pathophysiological study.
In a 47-year-old male with Ménétrier's disease (protein-losing gastropathy) the histamine-H2-receptor antagonist Cimetidine stops the protein loss and improves the clinical condition. Gastric perfusion studies on net and bidirectional ionic fluxes, protein secretion rates, and permeability, with simultaneous recording of the transmural electrical potential difference indicate that Cimetidine decreases a paracellular protein secretion by 'tightening' the tight junctions of the gastric epithelium.
Cimetidine in patients with gastric ulcer: a multicentre controlled trial.
Forty-five adult outpatients with endoscopically confirmed gastric ulceration completed a double-blind trial of either cimetidine (1 g/day) or placebo. After six weeks 18 of the 23 patients receiving cimetidine showed complete ulcer healing compared with only six of the 22 patients receiving placebo. The cimetidine group also had fewer days with pain than the placebo group but the difference was not statistically significant. Cimetidine therefore seems to promote healing of gastric ulcers without severe side effects, although its effect on pain is less pronounced than in patients with duodenal ulcers.
[Treatment of doudenal ulcer with cimetidine--an H2 receptor antagonist].
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A pragmatic trial of cimetidine in duodenal ulcer patients.
Fifty-eight outpatients with a clinical and radiological diagnosis of duodenal ulcer completed a double-blind randomized trial of the effect of cimetidine on ulcer symptoms. Patients normally treated in general practice were included in the trial. The patients in the treatment group received cimetidine 1 g daily and the controls received inactive tablets. The treatment period was four weeks. During the last nine days 18 (60%) of 30 cimetidine-treated patients were symptom-free against 5 (18%) of 28 controls (P less than 0.005). The antacid consumption, the number of days with pain and the number of hours with pain also differed significantly in the two groups. Apart from a transient rash in one patient no important clinical side-effects were noted. The serum creatinine rose slightly in the cimetidine-treated patients.
Transmural ionic fluxes and electrical potential difference in the human jejunum during perfusion with a dihydroxy bile acid.
Perfusion studies of the proximal jejunum were performed in healthy volunteers to define the influence of glycochenodeoxycholic acid (GCDC) 2.5 mmol/1 on the net movements of water and electrolytes, the bidirectional fluxes of sodium, potassium, and chloride, and the transmural electrical potential difference (PD). The flux data supported the notion that active sodium transport is inhibited by luminal GCDC, which on the other hand elicits active secretion of chloride. PD was 3 +/- 1 mV, lumen negative, and was not influenced by GCDC. The flux data fit a previously proposed model for the GCDC effect.
Effect of glycochenodeoxycholic acid on unidirectional transepithelial fluxes of electrolytes in the perfused human ileum.
Perfusion studies of the terminal ileum were performed in healthy volunteers to define the influence of a dihydroxy bile acid, glycochenodeoxycholic acid (GCDC) 2.5 mmol/l, on the mechanisms of electrolyte transport. Net movements of water and electrolytes, bidirectional fluxes of sodium, potassium, and chloride, and the transmural electrical potential difference (PD) were measured simultaneously. The results supported the notion of an active mechanism for sodium and chloride transfer. GCDC evoked net secretion of water and electrolytes, and decreased the mucosa to serosa flux of chloride, There was a tendency that the latter also applied to sodium and potassium. During bile acid perfusion active secretion of chloride occurred. PD was 16 +/- 4 mV, lumen negative, and was not influenced by GCDC. In conclusion, we propose a model for the GCDC effect.
Bile acid metabolism after jejunoileal bypass operation for obesity.
Bile acid metabolism and duodenal bacterial flora were studied in 12 obese patients before and 1-2 months after jejunoileal bypass operation, either including 37.5 cm jejunum and 12.5 cm ileum (Type I) or 12.5 cm jejunum and 37.5 cm ileum (Type III). The cholic acid pool size was unchanged after type I, but decreased after type III, bypass. The daily fractional turn-over of cholic acid increased about five times after both types of operation. The synthesis rate of cholic acid increased after both types of bypass, but more after type I than after type III. In duodenal bile the ratios of cholic to taurine conjugates increased after type I, but were unchanged after type III bypass, whereas the ratio of cholic to chenodeoxycholic acid was unchanged after both types of bypass. The bacterial flora and the occurrence of free bile acids in the fasting duodenal contents did not change after either of the two types of bypass operation. It is concluded that jejunoileal bypass results in marked disturbances in the bile acid metabolism. Surprisingly, these are most severe after bypass including the longest ileum, possibly because of insufficient stimulation of the bile acid synthesis in this type of operation.
Congenital chloridorrhoea. A question of reversed brush border transport processes and varying junctional tightness.
The surprising results of intestinal perfusion studies in an 8-month-old child with congenital chloridorrhoea offered a unique opportunity not only to elucidate the underlying defect, but also to test the adequacy of proposed models for normal intestinal transport. In ileum Na, K and Cl as well as water were secreted and HCO3 absorbed. Lumen was 91 mV negative to blood. Only Cl was transported against both electrical and chemical gradients, but discrepancies between observed and predicted Na flux ratios suggested the presence of a Na-absorbing mechanism as well. Mucosa was impermeable to Cl from the lumen side. 2.5 mM glycochenodeoxycholic acid (GCDC) mediated Na and water absorption and abolished any transport of Cl. PD was -95 mV. In colon a similar pattern was observed and mucosa to serosa fluxes of Cl were abnormally low. Rectal PD was -116 mV. GCDC made the epithelium more absorptive in function, but contrary to ileum the effect was due to an increase of Na and Cl fluxes from mucosa to serosa. The patient was at that time in severe electrolyte imbalance. He was reinvestigated three months later when he was in a good clinical condition with normal serum electrolytes. Net transfer of electrolytes and water and bidirectional fluxes of Cl and K were unchanged while bidirectional Na fluxes had increased considerably and PD decreased to -18 mV. Rectal PD was -45 mV. In jejunum water and electrolyte transport were normal and PD -3 mV. It is tentatively concluded that the abnormal transport in ileum is due to an inversion of the brush border transport processes, which also satisfies the paradoxical effects of GCDC. Furthermore, Na and Cl seem to migrate through separate pathways. A varying degree of junctional tightness, which is almost completely cationic, may be responsible for the functional differences observed in resonse to improvement of the general electrolyte status.
Regional ileitis (Crohn's disease). I. Kinetics of bile acid absorption in the perfused ileum.
Bile acid absorption was studied by steady state perfusion technique in the ileum of 11 patients with regional ileitis (Crohn's disease). By computerizing absorption kinetics the presence of an active transport of glycochenodeoxycholic acid (GCDC) was rendered probable by finding a saturable transport system and a competitive absorption between conjugated bile acids. At the time of investigation 5 patients had no diarrhoea, whereas 6 patients had diarrhoea as defined from the amount of faecal output. In the former group the faecal bile acid excretion was low, the ileal absorption of GCDC high, and judged from the xylose absorption the ileal absorption surface large compared to the latter group, in which the faecal bile acid excretion was high, the ileal absorption of GCDC low, and the ileal absorptive surface small. It is concluded that malabsorption of bile acids in the ileum may be of significant physiological importance in the pathogenesis of diarrhoea in patients with regional ileitis.