Involvement of cardiac, respiratory and gastrointestinal functions in neural responses to stressful events.

In the stress concept, fight and flight situations as well as other CNS-controlled reaction patterns for alertness to danger have to be followed by or integrated with a restorative "build-up" process in order to maintain homeostasis. The "build-up" process can be studied physiologically for example after regular exercise or training. Under these conditions there is a decrease in resting sympathetic adrenergic activity and an increase in the parasympathetic vagal activity. A theoretical model for the "build-up" process in psychosomatic gastroenterology has previously been presented. The present paper deals with the "build-up" process in cardiovascular and respiratory tract diseases seen in athletes. Anorexia nervosa related to excess physical training is also discussed as well as the "build-up" process in severe obesity and psychosomatic gastroenterological disorders.

The intragastric milieu during gastric ulcer treatment with pirenzepine 50 mg b.i.d. or cimetidine 400 mg b.i.d.

In a double-blind randomised four-center trial 43 patients with gastric ulcer (20 men, 23 women; mean age 52.2 years) were treated with either pirenzepine (P) 50 mg b.i.d. (n = 24) or cimetidine (C) 400 mg b.i.d. (n = 19) during six weeks. In ten patients gastric juice was examined before and at the end of the treatment for concentration and type of the microbial flora, and for nitrite concentration. After six weeks 83% of the patients in both groups were either symptom-free or clearly improved. In 15/24 patients on P (62.6%) and in 13/18 on C (72.2%) the ulcer(s) were healed at the time of control endoscopy. In the ten patients investigated, intragastric concentrations of fungi, bacteria, and nitrite were not significantly changed by the treatment. In gastric ulcer, treatment with pirenzepine 50 mg b.i.d. or cimetidine 400 mg b.i.d. during six weeks does not result in significant microbial overgrowth or generation of nitrite.

GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease.

An interview-based rating scale consisting of 15 items for assessment of gastrointestinal symptoms in irritable bowel syndrome and peptic ulcer disease has been developed. The interrater reliability was estimated by means of independent and simultaneous duplicate ratings by two raters in 20 cases and ranged from 0.86 to 1.00. The scale was easy to apply and proved to be useful in comparing the effectiveness of different modes of treatment in two clinical trials.

The effect of gastric secretion on orocoecal transit time measured with the hydrogen (H2) breath test.

Orocoecal transit time was studied by means of a hydrogen (H2) breath test after a standard meal in patients with peptic disease before and during treatment with ranitidine, in patients with gastric achlorhydria, and in healthy acid-secreting volunteers. Treatment with ranitidine prolonged the orocoecal transit time in patients with peptic disease from 201.9 +/- 18.3 (SEM) to 242.3 +/- 18.3 min (p less than 0.05). Also in patients with achlorhydria, the orocoecal transit time was prolonged (276.2 +/- 20.3 min), compared to the control group of healthy acid-secreting volunteers (213.5 +/- 15.7 min), (p less than 0.05). The orocoecal transit time did not correlate with gastric bacterial concentrations in the groups investigated, nor with the subjects' age. It was not correlated to the pH in the gastric juice of acid-secreting individuals, either with or without treatment. As gastric emptying was not evaluated in this study, it is impossible to state whether gastric stasis or inhibited small bowel motility, or both, cause the delayed transit in achlorhydria and during treatment with ranitidine. We suggest that the reduction of gastric juice volume could be the cause.

Rectosigmoid motility response to beta-adrenoceptor stimulation in patients with the irritable bowel syndrome.

Patients with the irritable bowel syndrome were studied with regard to the effects of beta-adrenoceptor agonists on rectosigmoid motility. Pressure was recorded with a continuously inflated balloon in the upper rectum and recorded from a pressure catheter in the sigmoid colon. On different days the beta-2 agonist terbutaline, the beta-1 agonist prenalterol, and placebo, respectively, were administered intravenously after a control period. During each examination contractile activity was quantified for three consecutive periods of 25 min. Terbutaline in a total dose of 0.50 mg decreased sigmoid motility index significantly from 3.0 +/- 0.6 (SEM) to 1.1 +/- 0.3 kPa X min (p less than 0.01). After less than or equal to 5 mg prenalterol no significant changes of motility index were observed. After placebo an increase, although not significant, in contractile activity was seen compared with the initial control period. Rectal motility indices were low and not changed by the beta agonists. The serum concentrations of the drugs were within the therapeutic limits used in clinical practice and caused a dose-dependent increase of both systolic blood pressure and heart rate. It is concluded that beta-2 adrenoceptor stimulation significantly decreases sigmoid motility whereas the motility index seems to be unaffected by beta-1 adrenergic stimulation.

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.

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.

The hydrogen (H2) breath test. Sampling methods and the influence of dietary fibre on fasting level.

Three end-expiratory breath hydrogen (H2) sampling methods were compared in a patient group (n = 12) and a laboratory staff group (n = 12) on two separate occasions. H2 samples obtained with each method showed significantly different concentrations (p less than 0.001) but no significant differences in coefficient of variation when individual triplicate samples were evaluated. There was a high correlation between the breath H2 concentrations obtained by the three methods (r = 0.93-0.96). Fasting breath H2 values after an overnight fast and an unrestricted diet the day before the investigation were compared with values obtained after an overnight fast and a low-fibre diet the day before the test in two patient groups (n = 39 and 39) with a comparable distribution of diagnoses and in one group of healthy volunteers (n = 17). Fasting breath H2 concentrations were significantly lower after a low-fibre diet in the patient groups (p less than 0.005) and in healthy volunteers (p less than 0.02). We conclude that each of the three end-expiratory sampling methods can be chosen for use in H2 breath tests depending on suitability and convenience and that a low-fibre diet the day before the H2 breath test lowers fasting breath H2 concentration.

Effects of beta-adrenoceptor stimulation on rectosigmoid motility in man.

Effects of selective beta-adrenoceptor agonists on rectosigmoid motility during prolonged rectal distension were studied in 12 healthy volunteers in a double-blind, randomized fashion. Continuous distension was performed with a balloon in the proximal part of the rectum. Pressure was recorded by this balloon and by a catheter in the sigmoid. Contractile activity was quantified for three consecutive periods of 25 min. On separate days prenalterol (beta-1 agonist), terbutaline (beta-2 agonist), and placebo, respectively, were administered intravenously preceded by a control period. Terbutaline, 0.5 mg intravenously, was followed by a significant decrease of sigmoid motility from 4.3 +/- 1.5 (SEM) kPa X min to 2.9 +/- 1.0 kPa X min (P less than 0.01) and of rectal motility from 4.3 +/- 1.3 to 2.4 +/- 0.7 kPa X min (P less than 0.05). After placebo a slight, but not significant, increase of contractile activity was seen compared to the initial control period. The effects of prenalterol, 1.0 and 4.0 mg intravenously, on motility did not differ from that of placebo infusion. Both drugs caused a dose-dependent increase of systolic blood pressure and of heart rate. The study shows that beta-2-adrenoceptor stimulation decreases rectosigmoid colonic pressure in man, while effects of beta-1 stimulation on motility index do not differ from that of placebo.

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.

Symptom profiles in chronic peptic ulcer disease. A detailed study of abdominal and mental symptoms.

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.

Pirenzepine versus cimetidine in duodenal ulcer treatment. A clinical and microbiological study.

The therapeutic efficacy of pirenzepine (PIR) and cimetidine (CIM) in duodenal ulcer and their effects on the intragastric milieu have been studied in a double-blind multicentre trial. Seventy-nine patients with endoscopically proven duodenal ulcer were randomly allocated to 4 weeks' treatment with either 50 mg PIR twice daily or 400 mg CIM twice daily. In addition to clinical and endoscopic evaluation and registration of side effects and laboratory test results, endoscopically obtained gastric juice was cultured and its nitrite concentration was measured before and at the end of the treatment. Seventy-five patients completed the study. The treatment groups were comparable with regard to age, sex, smoking habits, and consumption of coffee and alcohol. After 4 weeks, 27 of 37 patients (73%) in the PIR group were completely healed, compared with 29 of 38 (76%) in the CIM group (NS). The number of patients with side effects was similar in both groups, but side effects of antimuscarinic type were more frequently reported by patients in the PIR group. Intragastric microbial concentrations increased significantly during treatment in both groups but remained well within normal limits. No single nitrite concentration before or after treatment exceeded the normal range. In conclusion, the two drugs were about equally effective in the short-term treatment of duodenal ulcer disease. In the doses given they did not adversely affect the intragastric milieu.

Stress management in the long-term treatment of peptic ulcer disease.

The definition of stress varies from author to author. Whether or not it is experienced depends on the perception of the potentially stress-producing event. Stress can be induced experimentally in animals or human beings in various ways and can arise from a person's occupation, leading to adverse effects such as hypertension, cardiac alterations, increase in gastric acid secretion and the occurrence of peptic ulceration. In man, peptic ulceration may be linked to a dependence-independence conflict. The incidence of duodenal ulcer has been shown to be higher in those from broken homes than from normal homes. In 103 duodenal ulcer patients with high scores for stressful life events followed-up over a 15 month period, the outcome was more favourable in those who received psychotherapy plus intermittent pharmacotherapy than in those who received intermittent pharmacotherapy alone.