G. Dotevall

Upper gastrointestinal and mental symptoms in the irritable bowel syndrome.

Gastrointestinal and mental symptoms were assessed in 101 outpatients with the irritable bowel syndrome (IBS). A normal female population was used for comparison of mental symptoms. By definition all patients had abdominal pains and/or change of bowel habits (constipation or diarrhoea, or both) but no demonstrable organic disease. Upper gastrointestinal symptoms without peptic ulcer disease were reported by 87% of the patients. Mental symptoms were reported by almost all patients. Symptoms of anxiety, fatiguability, hostile feelings, sadness, and sleep disturbances were seen significantly more often among IBS women than in the controls. We conclude that patients with IBS frequently have upper gastrointestinal and mental symptoms that should be taken into account in the therapeutic management and evaluation of new modes of treatment.

Chronic Inflammatory Bowel Disease in Patients with Coeliac Disease

Six patients with coeliac disease and inflammatory bowel disease are described. Of special interest were two patients with coeliac disease and dermatitis herpetiformis and ulcerative colitis, one of whom also had sclerosing cholangitis. Three patients had both coeliac disease and ulcerative colitis, and one of them also had sclerosing cholangitis. In one patient with coeliac disease Crohns disease of the small bowel was diagnosed. There seems to be association between coeliac disease without dermatitis herpetiformis, and ulcerative colitis. The possible combination of coeliac disease and inflammatory bowel disease deserves more attention than it has hitherto received.

Symptom Profiles in Chronic Peptic Ulcer Disease

Abdominal and mental symptoms were assessed in 103 outpatients with chronic peptic ulcer disease. Patients with present symptoms and a history of duodenal or prepyloric ulcer were included if they had no other disorder requiring treatment. A normal female population was used for comparison of mental symptoms. Besides the cardinal ulcer or acid-related symptoms, there was a high rate of indigestion and bowel dysfunction symptoms, usually associated with the irritable bowel syndrome. Mental symptoms were reported by almost all patients. Symptoms of anxiety, depression, and neurasthenia were seen significantly more often among the female patients than in the normal women. We conclude that a wide range of both abdominal and mental symptoms should be taken into account in the therapeutic management of peptic ulcer disease, in evaluation of clinical trials, and in studies of the natural history.

Effect of selective and non-selective antimuscarinics on rectosigmoid motility and gastrointestinal transit.

In 12 healthy volunteers, a rectosigmoid motility index (RSMI) was measured when either placebo, 0.5 mg atropine, or 5 mg pirenzepine was given intravenously as a single dose, double-blind, in random order after a control period of 30 min. Compared with the control period, atropine gave a significant decrease of the RSMI during the entire recorded period of 90 min, whereas pirenzepine inhibited RSMI only during the first two 15-min periods. In another series of experiments, gastrointestinal transit was assessed by means of a radiographic marker method. In healthy volunteers, gastrointestinal transit was estimated (n = 20) and gastric secretion was measured (basally and after modified sham feeding; n = 10) during oral medication with placebo, 50 mg pirenzepine twice daily, or 17.5 mg benzilonium bromide twice daily. In 10 of the volunteers gastrointestinal transit was also estimated with 35 mg benzilonium bromide twice daily, and in the other 10 volunteers with 0.6 mg L-hyoscyamine twice daily. The number of retained markers was significantly lower during pirenzepine than during L-hyoscyamine treatment. Neither dose of benzilonium bromide changed the transit of markers. Compared with non-selective antimuscarinics, the effect of pirenzepine was differential: with equipotently acid-reducing doses the decrease of the RSMI after pirenzepine lasted shorter and gastrointestinal transit was accelerated.

Inhibition of Gastric Acid Secretion by Pirenzepine (LS 519) in Man

Pirenzepine is a new tricyclic drug used in the treatment of peptic ulcer disease. The effect of two doses of pirenzepine (25 mg twice daily and 50 mg thrice daily) was examined in ten healthy volunteers during basal acid secretion and under stimulation with two doses of pentagastrin (0.166 microgram/kg . h and 1 microgram/kg.h given as continuous intravenous infusion). Serum drug concentrations were determined by radioimmunoassay, and parallel studies of the salivary function were performed. Pirenzepine, 25 mg twice daily, reduced basal acid output by 50% and 55%, respectively, and inhibited stimulated acid output by 31% and 26%, respectively. The higher dose of pirenzepine, 50 mg thrice daily, augmented the effect insignificantly despite markedly increased serum drug levels. The recommended therapeutic dose of 25 mg twice daily gave no salivary inhibition. Pirenzepine may have an anticholinergic effect on the parietal cell, although systemic side effects were not seen. Pirenzepine does not competitively inhibit pentagastrin-stimulated acid secretion.

The effect of pirenzepine on basal, pentagastrin- and insulin-stimulated gastric acid secretion in patients with peptic ulcer disease.

The effect of pirenzepine on basal and stimulated acid secretion was tested in five patients with peptic ulcer disease and gastric hypersecretion. Two types of stimulation were compared, namely pentagastrin by intravenous infusion (1 microgram/kg/h) and hypoglycaemia induced by insulin given subcutaneously (0.125 IU/kg). Basal acid output/30 min was reduced by 44% and 69%, respectively. Pentagastrin-stimulated acid output was reduced by 30%/120 min, and insulin-stimulated acid output by 47%. The reduction was similar during the first and second hour of stimulation in both series. These results strengthen our previous impression that pirenzepine may interfere with cholinergic receptors at the parietal cell level. As the inhibition of gastric acid secretion by pirenzepine is similar to that produced by oral doses of cimetidine, pirenzepine may be useful in the treatment of peptic ulcer disease.

Failure of Beta-Adrenergic Stimulation to Affect Cholecystokinin-Stimulated Sigmoid Motility in Man

Sigmoid motility, stimulated by the octapeptide of cholecystokinin (OP-CCK) and the effects of beta-adrenoceptor agonists, was studied in 12 healthy subjects in a randomized, double-blind fashion. Sigmoid pressure was recorded 18-20 cm from the anus, and contractile activity quantified as the area under pressure waves for three 25-min periods. OP-CCK (sincalide), 80 ng X kg-1 X h-1, was continuously infused throughout each session, resulting in a high sigmoid motility index. Preceded by a control period, terbutaline (beta-2 agonist), prenalterol (beta-1 agonist), or placebo was injected on 3 separate days. After 1 mg + 4 mg prenalterol or 0.25 mg + 0.25 mg terbutaline intravenously no significant changes in motility pattern were seen compared with the control period. Terbutaline and prenalterol infusions were followed by a dose-dependent increase of systolic blood pressure and heart rate. After placebo no effect on blood pressure or heart rate was seen. The study shows that CCK significantly enhances sigmoid motility in man and that selective beta-adrenergic agonists do not show any inhibitory influence on colonic motility stimulated with CCK. Since terbutaline inhibits sigmoid and rectal motility in man during rectal distention, it is suggested that the inhibitory effect of beta-2-adrenoceptor agonists may be dependent on the mode of background stimulation of the colon.