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Biomedical subjects

J Rask-Madsen

Publications and source records attributed to J Rask-Madsen.

At least 109 records · Page 6Linked to original sources
PubMed1983

Colonic transport of water and electrolytes in a patient with secretory diarrhea due to collagenous colitis.

Whole colon perfusion studies and measurements of luminal prostaglandin E2 were carried out in a 41-year-old female with collagenous colitis to investigate pathophysiological mechanisms for the diarrhea. Biopsies of the colorectal mucosa had revealed a continuous 25- to 60-micron subepithelial collagenous layer, but normal junctional complexes and capillaries. When the patient fasted, the diarrhea persisted and fecal electrolytes, as estimated from the concentration of sodium, potassium, and their anions, accounted for all the osmolality (284 mosm/kg) of stool water, the pH of which was above 8.0. The lumen-negative electrical potential difference in the rectum was -64 mV vs -45 +/- 2 mV (mean +/- SEM) in healthy controls. Profuse secretion of fluid and electrolytes occurred during colonic perfusion with saline. Transport of sodium appeared to be passive with flux ratios equal to those predicted for passive sodium movements, while chloride transport against a steep electrical gradient indicated active secretion. Perfusion with an "ileal output"-like solution decreased fluid and electrolyte secretion, suggesting that bicarbonate, in addition to chloride, may be a major determinant of secretion rates. Since immunoreactive prostaglandin E2 levels following in vivo equilibrium dialysis of feces ranged from 555 to 650 pg/ml vs 55 to 235 pg/ml (99% confidence limits) in healthy controls, it is speculated that prostaglandins synthesized locally in response to mucosal hypoxia might be the mediators of anion secretion.

Adult↗
PubMed1983

Effect of carbenoxolone on gastric prostaglandin E2 levels in patients with peptic ulcer disease following vagal and pentagastrin stimulation.

The influence of oral carbenoxolone sodium (50 mg X 3 daily) on prostaglandin E2 release into gastric juice has been examined in nine peptic ulcer patients (duodenal ulcer, n = 6; prepyloric ulcer, n = 1; gastric ulcer, n = 2) during modified sham feeding and following bolus stimulation of acid secretion by pentagastrin (6 micrograms/kg). Carbenoxolone increased the overall mean of prostaglandin E2 concentrations in gastric juice following modified sham feeding by 32 +/- 9% (mean +/- SEM; P less than 0.02) and decreased the acidity slightly but significantly (P less than 0.05). A marked rise in prostaglandin E2 levels (46 +/- 11%; n = 5; P less than 0.02) was observed in for duodenal ulcer patients and the patient with a prepyloric ulcer responding to therapy (i.e., pain relief and ulcer healing within 4 weeks of treatment). A significant peak (P less than 0.05) related to modified sham feeding was observed only during medication, while a late gradual increase in prostaglandin E2 levels--not associated with vagal stimulation--occurred both in control and carbenoxolone experiments. No significant differences were observed following pentagastrin stimulation. The initial peak in prostaglandin E2 levels observed during medication favours the notion that the mechanism of drug action relies on inhibition of enzymatic degradation while the late increase in prostaglandin E2 levels may be explained by artificial prostaglandin formation during the aspiration procedure.

Adult↗
PubMed1981

Release of prostaglandin E2 into gastric juice during stimulation of muscarinic- and gastrin receptors in dogs and in humans.

To investigate the causal relationship, if any, between gastric PG formation and gastric acid output, the release of PGE2 into gastric juice has been studied in eight beagle dogs with a gastric fistula, using sustained half-maximal stimulation by bethanechol and pentagastrin, and in eight duodenal ulcer patients, using the combined sham feeding/pentagastrin test. Immunoreactive PGE2 was determined by a method validated by gas chromatography-mass spectrometry and PGE2 values were normalized by expressing them as ng PGE2 released per meq H+ secreted. In the dogs "steady state" PGE2 output (0.4-10 ng/meq H+) was interrupted during continuous i.v. pentagastrin infusion by symmetrical peaks (50-60 minutes of duration) with a maximum of 24 +/- 3.1 ng/meq H+ (mean +/- SEM). During bethanechol stimulation the rhythmic variations were smaller, but the median values for the periods 30 to 180 or 240 minutes significantly (p less than 0.01) higher (3.9-46 ng/meq H+) than in pentagastrin experiments (0.8-20 ng/meq H+). In humans the peak PGE2 output during sham feeding (3.4-41 ng/meq H+) was significantly (p less than 0.02) larger than following bolus stimulation (6/micrograms/kg) by pentagastrin (2.2-18 ng/Meq H+). The findings are consistent with the hypothesis that activation of muscarinic receptors represents the physiologic mechanism by which gastric release of PGs is regulated. Cyclic variations in gastric PG formation appear to occur in response to vagal stimulation since the peaks in PGE2 output were preceded by increased myoelectrical activity (i.e. mean contractile index).

Adult↗
PubMed1981

Prostaglandin E2 in jejunal fluids and its potential diagnostic value for selecting patients with indomethacin-sensitive diarrhoea.

Since prostaglandins (PGs) appear to be important in the pathogenesis of secretory diarrhoea, a radioimmunoassay for determination of PGE2 was applied to purified samples of jejunal fluids aspirated at the ligament of Treitz. Studies on validation of the assay system included quantification of PGE2 following alkali-treatment of the samples, variation of the sample volume, and fractionation of immunoreactive- and tracer PGE2. In addition, the specificity of the assay system was confirmed by gas chromatography--mass spectrometry. In healthy volunteers (n = 22) the PGE2 concentration range was 5--205 pg/ml (99% confidence limits). Alcohol addicts (n = 27) with diarrhoea or steatorrhoea had PGE2 levels within the normal range. Values beyond the 99% upper confidence limit were observed in ten out of seventeen patients with chronic diarrhoea (205--340 pg/ml) and two out of fifteen patients with intermittent diarrhoea (265 and 275 pg/ml) classified as irritable bowel syndrome. In six patients with high PGE2 concentrations indomethacin treatment (25 mg x 4 daily) halved the associated diarrhoea and reduced PGE2 concentrations to normal levels. Subsequently, a double-blind multiple randomized clinical trial was carried out in two single patients. Indomethacin proved to be effective in preventing diarrhoea only in the patient with a raised PGE2 level (P less than 0.005).

Alcoholism↗
PubMed1981

Prostaglandin E2-mediated secretory diarrhea in villous adenoma of rectum: effect of treatment with indomethacin.

Biochemical and clinical evidence is presented to indicate that prostaglandin (PG)E2 is the mediator of fluid and electrolyte secretion by villous adenomas of the rectum. A 64-yr-old man with a 2-mo history of mucous diarrhea had, on admission, prerenal uremia, severe hyponatremia, and hypokalemia. At sigmoidoscopy an 11 X 11-cm villous adenoma of the rectum was revealed. The rectal fluid discharge was 1800-1825 ml/day, with sodium and potassium concentrations of 150 and 12 mEq/L, respectively. Immunoreactive PGE2 levels in the rectal effluents were high (viz. 1160-1250 pg/ml vs. 200-395 pg/ml) compared with those in stool water from patients with infectious diarrhea. The concentration of vasoactive intestinal polypeptide (VIP) in the tumor was lower (viz. 10.5 pmol/g vs. 100-700 pmol/g) than in normal colonic mucosa. Indomethacin treatment (24 mg X 4 daily) reduced the rectal PGE2 excretion from 2.2 to 0.3 microgram/day and caused a decrease in the rectal fluid loss of 850 ml/day associated with a similar reduction in rectal sodium excretion. Discontinuing medication, a rise in the rectal excretions of PGE2, fluid, and sodium was observed. In conclusion, PGE2 formation in the villous adenoma appears to be the cause of fluid secretion by the abnormal tumor epithelium. The use of PG synthetase inhibitors may facilitate the preoperative correction of severe fluid-electrolyte deficits in patients with large villous adenomas of the rectum.

Adenoma↗
PubMed1979

Prostaglandins and chronic diarrhoea: methodological problems.

In order to determine the arterio-venous difference in circulating prostaglandin levels the isotope derivative technique was applied to rat plasma for measurements of prostaglandin E2 (PGE2). No arterio-venous difference was observed if the blood was collected without precautions to avoid in vitro prostaglandin production in the sampling tube. In contrast, inhibition of the in vitro prostaglandin release by the infusion of indomethacin into the catheter from which the blood was drawn, showed PGE2 levels in the right atrium of 60 +/- 20 pg/ml (mean +/-SD; N = 8), and peripheral levels insignificantly different from zero. A significant difference in PGE2 levels of right atrial plasma from fed and fasted rats was observed without the use of in vitro indomethacin in blockade (210 +/- 70 pg/ml; N=4, and 330 +/- 35 pg/ml; N = 4, respectively). This difference could not be reproduced if indomethacin was infused into the catheter (60 +/- 20 pg/ml; N = 8 and 90 +/- 35 pg/ml; N = 5, for fed and fasted rats, respectively). Measurements by radio-gas-liquid-chromatography of the arachidonic acid plasma level showed values of 6.8 +/- 1.6 micrometers (N = 7) and 12.0 +/- 3.4 micrometers (N = 7) for fed and fasted rats, respectively. It is suggested that the higher level of PGE2 (without indomethacin) in fasted rats reflects that of arachidonic acid. The present available methods for the determination of primary prostaglandins and prostaglandin metabolites are discussed with respect to their value not only in physiological studies on fluid and electrolyte transport in the gut, but also for clinical use.

Animals↗
PubMed1978

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.

Adult↗
PubMed1978

The electrical potential difference and impedance between CSF and blood in unanesthetized man.

The electrical potential difference (PD) between cerebrospinal fluid (CSF) and blood has been studied extensively in animals. To obtain data from man the PD and impedance were recorded from the lumbar subarachnoid space of thirteen unanaesthetized patients with a presumably normal blood--brain barrier. The spontaneous PD ranged from 1 mV to 5 mV, CSF positive to blood. Hyperventilation and CO2-inhalation changed the PD with a mean slope of deltaPD/deltapHa of --4.16 mV/pH. The CSF-blood PD in unanaesthetized man is similar in direction to that found in dogs, goats and rats, but its sensitivity to change in arterial pH may be less.

Adult↗
PubMed1977

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.

Adult↗
PubMed1977

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.

Adolescent↗
PubMed1977

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.

Adult↗
PubMed1977

Effect of amiloride on electrical activity and electrolyte transport in human colon.

It is not known whether factors other than Na transport are involved in generating the electrical potential difference (PD) across the human colonic wall. Therefore, experiments were performed in which the effect of amiloride on PD and ion transport was evaluated in the in vitro short-circuited human colon. In control periods the short-circuit current (Isc) was 2.9 +/- 0.3 (mean +/- S.E.M.) muEq per hr per cem2, while the corresponding net transfer of Na and Cl was 4.6 +/- 0.4 and 1.4 +/- 0.1 respectively. The residual flux was insignificantly different from zero. Amiloride caused a prompt, but reversible, decrease in Isc, PD, and conductance when added to the mucosal sie,dbut only a relatively small reduction of the mucosa to serosa fluxes of Na occurred. Bidirectional Cl fluxes were unchanged while the residual flux increased significantly. It is proposed, therefore, that some ions other than Cl (presumably mucosa to serosa fluxes of H and/or serosa to mucosa fluxes of HCO3) are the main counter ions for actively transported Na in the large bowel. Experiments performed in vivo showed that the rectal PD decreased exponentially from -46 mV +/- 0.8 TO -27 MV +/- 0.3 (mean +/- S.E.M.) following rectal instillation of 10-3 M amiloride. The half-time required for this effect was less than 13 seconds.

Adult↗
PubMed1977

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.

Adult↗