Kristina Sjölund

Autonomic vagal nerve dysfunction in patients with ulcerative colitis

Autonomic nerve function was evaluated in 40 patients with total ulcerative colitis and in 25 patients with irritable bowel syndrome by three established non-invasive tests based on the heart reactions to deep breathing (E/I ratio) and tilt (acceleration and brake index). None of the patients were diabetic. Most of the patients with ulcerative colitis were clinically and biochemically inactive; 10 had previously undergone colectomy. The results were compared with a control group consisting of 56 healthy individuals and 33 previously investigated patients with Crohns disease, 45% of whom demonstrated autonomic neuropathy (AN). Patients with ulcerative colitis had a significantly lower E/I ratio than controls in age-corrected values, indicating vagal nerve dysfunction. Altogether, 35% had signs of AN. In patients with irritable bowel syndrome 36% had evidence of AN, a figure in agreement with observations from other investigators. We conclude that AN is common in patients with ulcerative colitis, regardless of disease activity and previous colectomy. In contrast to a predominantly sympathetic dysfunction in Crohns disease, AN in ulcerative colitis was vagal.

Disturbed motilin and cholecystokinin release in the irritable bowel syndrome.

BACKGROUND The irritable bowel syndrome (IBS) is associated with motor abnormalities in the small intestine and colon. Neuropeptides may have an important role in initiating and regulating the intestinal motility. Motilin has been proposed to initiate the peristaltic reflex in the small intestine and cholecystokinin the gastrocolic reflex. METHODS In 18 patients with IBS and 11 healthy control subjects plasma motilin and cholecystokinin (CCK) concentrations were measured after intraluminal stimulation of water and a fat-rich meal. RESULTS The IBS patients had reduced motilin secretion after both water intake and the fat meal. In contrast, the fat meal elicited an exaggerated and prolonged CCK release in the IBS patients. CONCLUSIONS Disturbed motilin and CCK release may partly be responsible for the intestinal dysmotility in the IBS patients.

Effects of long-term treatment with oxytocin in chronic constipation; a double blind, placebo-controlled pilot trial.

Abstract  Background:  Oxytocin and its receptor have been found throughout the gastrointestinal (GI) tract, where it affects gut function. Clinically, we have noticed an improvement of bowel habits during lactation in constipated women. The aim of this study was to examine whether oxytocin has an effect on bowel symptoms and psychological well being in women with refractory constipation.

Small intestinal manometry in patients with systemic sclerosis.

Objectives The study explores, by the use of manometry, the frequency and severity of small intestinal involvement in patients with systemic sclerosis, and relates the manometric findings to clinical symptoms, radiology, and some intestinal regulatory peptides. Methods Stationary antroduodeno-jejunal manometry was used to study small bowel involvement in 10 patients with systemic sclerosis and dysmotility of the oesophagus or signs of malabsorption. Measurements were made during fasting, after a meal, and after octreotide administration and were then compared with a sex-matched control group of healthy individuals. Plasma samples were taken in order to analyse levels of motilin, peptide YY, cholecystokinin, and somatostatin. Results Manometry was abnormal, with signs of intestinal pseudo-obstruction in eight out of 10 patients. In the control group, one individual had an abnormal manometry, as a result of burst activity. The mean contractile amplitudes during fasting and periods after food, spontaneous phase III periods, and octreotide-induced activity complexes were significantly reduced in the systemic sclerosis group when compared with controls. None of the patients, including two with advanced manometric intestinal disturbances, had small intestinal dilatation when examined by radiography. The plasma peptide levels did not differ significantly between the two groups. Conclusions In eight out of 10 patients the manometric criteria for intestinal pseudo-obstruction were fulfilled, with a motility pattern consistent with both neuropathy and myopathy. The release of motility-regulating peptides was unaffected.

Is GIP a glucagon cell constituent

Summary“Gastric inhibitory peptide” or “glucose-dependent insulin-releasing peptide” (GIP) is a member of the gut hormone family. Its physiological action is thought to be related to its insulinotrophic effect.The occurrence and distribution of GIP was studied by immunohistochemistry. In all species examined including man, GIP immunoreactivity was found to reside in the glucagon cells of the pancreas and gut. Three pancreatic glucagonomas were found to contain numerous cells displaying GIP and glucagon immunoreactivity.The GIP antiserum used did not cross react with either pancreatic-type or gut-type glucagon (GLI).

Cholecystokinin Stimulation Leads to Increased Oxytocin Secretion in Women

OBJECTIVE To find out if cholecystokinin (CCK) stimulates the secretion of oxytocin in humans, and if there are any differences in secretion between healthy women and those with normal-transit constipation. DESIGN Prospective open study. SETTING Teaching hospital, Sweden. SUBJECTS 8 healthy female volunteers and 6 women with chronic refractory normal-transit constipation. INTERVENTIONS Subjects were fasted before experiments. On one day they were given emulsified corn oil and another an intravenous injection of 1 Ivy dog unit (IDU) CCK/kg body weight. Blood samples were taken before each experiment at 10 minutes and at the time the experiments started. Blood samples were also taken after each experiment at 10, 20, 30, 45, 60, 90 and 120 minutes. MAIN OUTCOME MEASURES Concentrations of CCK and oxytocin. RESULTS Ingestion of corn oil significantly increased the plasma concentration of CCK in both groups (healthy women p = 0.03 and constipated women p = 0.008). Injection of CCK also led as expected to hypercholecystokininaemia in both groups (p = 0.008 and p = 0.03, respectively). The corn oil increased oxytocin secretion in both groups (p = 0.02 and 0.03, respectively) and exogenous CCK increased the secretion still further (p = 0.008 and 0.03, respectively). CONCLUSIONS Both corn oil and injection of CCK led to an increased CCK concentration in plasma. Oxytocin was secreted in response to endogenous as well as exogenous CCK stimulation. There was no difference between healthy and constipated women in either parameter analysed.

Jejunoileal Bypass Changes the Duodenal Cholecystokinin and Somatostatin Cell Density

Background: In obese patients, jejunoileal bypass (JIB) has been used to induce weight reduction. Changes in the neuroendocrine system may be affected by the JIB-operation, because the proximal small intestinal mucosa has a rich supply of endocrine cells and peptidergic nerves. Materials and Methods: In 37 obese patients operated with JIB 1-30 years ago, small intestinal biopsies were taken at the duodeno-jejunal flexure, proximal to the anastomosis and from 5 unoperated obese persons and 20 normal weight patients. The tissue specimens were processed for immunocyto-chemical demonstration of cells/nerves containing: gastrin, cholecystokinin (CCK), secretin, gastric inhibitory peptide (GIP), motilin, somatostatin, serotonin, glicentine, peptide YY (PYY), neurotensin, vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and galanin. The number of different endocrine cell-types were counted per unit length of mucosa, and the density of the peptidergic nerves was assessed semiquantitatively according to a schematic scale. Results: JIB-patients had an increased density of CCK and somatostatin cells in the duodenal mucosa. The CCK cells displayed a changed reaction pattern, with a greater cell number reacting with an antiserum directed towards a non-amidated mid-sequence of procholecystokinin compared with the other groups. In obese unoperated patients, the density of PYY and secretin cells was decreased compared with the JIB-patients and the density of the GIP cells compared with both other groups. Conclusion: JIB induces an up-regulation of somatostatin and CCK precursor-containing cells in the duodenal mucosa. The time duration after the JIB did not seem to influence the results.

Covariation of plasma ghrelin and motilin in irritable bowel syndrome

We have previously shown that ghrelin is mainly localized to the stomach but also occurs, together with the prokinetic hormone motilin, in endocrine cells in the proximal small intestine. This study explored ghrelin and motilin concentrations in plasma in relation to gastrointestinal motility and whether plasma ghrelin is changed in patients with irritable bowel syndrome (IBS). Nine patients with severe IBS and 10 healthy subjects underwent stationary antro-duodeni-jejunal manometry; blood was sampled during similar motility phases in the two groups. The motility phases were monitored and blood samples were collected during fasting and after food intake. Plasma was analyzed for two forms of ghrelin (octanylated and desoctanylated) as well as for motilin. In IBS patients circulating motilin levels covaried with total ghrelin levels (r=0.90; p<0.004), octanylated ghrelin (r=0.77; p<0.02) and desoctanylated ghrelin (r=0.69; p<0.04). No such correlations were seen in the control group. Octanylated ghrelin comprised 35.3+/-3.9% (mean+/-SEM) of the total circulating ghrelin in the IBS patients compared to 40.4+/-4.5% (mean+/-SEM) in the control group (NS). Ghrelin covaried with motilin in plasma in IBS but not in plasma from healthy subjects. This suggests the two peptides act together in IBS.

Further Validation of the Visual Analogue Scale for Irritable Bowel Syndrome After Use in Clinical Practice.

The Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS), a self-rating questionnaire, was designed to measure symptoms and the effect of treatment in patients suffering from irritable bowel syndrome. The aim of this descriptive correlational study was to conduct further psychometric validation after the VAS-IBS had been used in clinical practice, translate it into English, and compare the results with controls. Forty-nine patients with irritable bowel syndrome (median age = 38 years old [range, 18–69 years]) were compared with 90 healthy persons (median age = 44 years old [range, 21–77 years]) who served as controls. The patients with irritable bowel syndrome completed 3 questionnaires: the VAS-IBS, the Gastrointestinal Symptom Rating Scale, and the Perception of Change of Symptoms. Controls completed only the VAS-IBS. Results showed that the VAS-IBS is a valid questionnaire that measures the degree of change of symptoms and discriminates between patients who have irritable bowel syndrome from those who do not. It is important to compare the VAS-IBS among different cultural populations so we suggest that the English version of the VAS-IBS should now be used in English-speaking countries and be further tested for validity and reliability with English-speaking patients.

Evaluation of gastric acid secretion at endoscopy with a modified Congo red test.

BACKGROUND Markedly decreased or absent gastric acid production is associated with a number of clinically significant conditions, and identification of patients with hypo/achlorhydria may be important. However, current methods of assessing impaired acid secretion are unreliable, time-consuming, and/or complex. The aim of this prospective study was to evaluate a modified endoscopic Congo red test for the diagnosis of hypo/achlorhydria by correlation with a standard gastric acid secretory test. METHODS One hundred six consecutive outpatients with or without dyspeptic symptoms referred for endoscopy were evaluated by using a modified endoscopic Congo red test and a standard test of gastric acid secretion. The modified endoscopic Congo red test suggested hypo/achlorhydria when there was no color shift or a shift of small extent (less than one third of fundic mucosa). Hypo/achlorhydria by the standard gastric acid secretory test was defined as a maximal acid output of less than 6.9 mmol/hour in men and 5.0 mmol/hour in women. RESULTS The accuracy of the modified endoscopic Congo red test for the diagnosis of hypo/achlorhydria was 0.98 (95% CI [0.93, 0.99]). The sensitivity was 1.0 (95% CI [0.92, 1.00]) and specificity 0.96 (95% CI [0.88, 0.99]). All patients tolerated the modified endoscopic Congo red test well. CONCLUSION The modified endoscopic Congo red is an accurate, simple, fast, inexpensive, and well-tolerated chromoendoscopic method for identification of patients with hypo/achlorhydria during routine upper endoscopy.