Gastric accommodation in non-ulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function.

BACKGROUND: The pathophysiological mechanisms in non-ulcer dyspepsia are incompletely understood. AIMS: To compare gastric motor and sensory functions in Helicobacter pylori positive or negative patients with non-ulcer dyspepsia. PATIENTS: Seventeen patients with non-ulcer dyspepsia and 16 asymptomatic controls. METHODS: The following were evaluated: gastrointestinal symptoms; gastric emptying and orocaecal transit of solids; abdominal vagal function; gastric compliance; fasting and postprandial gastric tone and phasic contractions; symptoms during ingestion of cold water and during the distension of an intragastric bag; and somatic sensitivity and personality profile (Minnesota Multiphasic Personality Inventory, MMPI). RESULTS: Gastric accommodation was reduced in H pylori negative dyspeptics relative to controls; the degree of accommodation was unrelated to H pylori status in dyspeptics. Increased postprandial gastric sensation was more frequent among H pylori positive patients (4/5 H pylori positive versus 4/12 H pylori negative patients). Intragastric meal distribution and orocaecal transit were normal; gastric emptying at four hours was abnormal in 4/17 patients. Vagal dysfunction was rare. Eight of 17 patients had somatisation or depression on MMPI. CONCLUSION: Impaired gastric accommodation is frequent in non-ulcer dyspepsia and seems to be unrelated to vagal efferent dysfunction. H pylori infection does not seem to influence gastric accommodation, but is associated with heightened sensitivity in dyspeptics. Therapeutic approaches that restore normal postprandial accommodation and gastric sensitivity should be tested in non-ulcer dyspepsia.

Medium-term effects of a new 5HT3 antagonist, alosetron, in patients with carcinoid diarrhoea.

BACKGROUND: Carcinoid diarrhoea is associated with rapid small bowel and proximal colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT3) antagonist restores postprandial colonic tone towards normal in carcinoid patients. AIMS: To evaluate the medium-term effects of an oral 5HT3 antagonist, alosetron, on symptoms, stool fat, and transit in patients with carcinoid diarrhoea. METHODS: In 27 patients with carcinoid diarrhoea, symptoms were recorded daily and gastrointestinal transit was measured by scintigraphy in a three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group, four week study. Placebo was given during the first week. Loperamide (2 mg capsules) was used as rescue medication. RESULTS: There were numerical improvements in median diarrhoea score, stool weight, loperamide use, and overall colonic transit at four hours, but no overall significant drug effect was shown. Alosetron reduced the proximal colon emptying rate (p < 0.05 in 20 evaluable comparisons), but did not significantly alter small bowel transit. CONCLUSIONS: Alosetron retardation of proximal colonic emptying in patients with carcinoid diarrhoea confirms the potential role of a 5HT3 mechanism in this disorder. Doses of alosetron higher than 2.0 mg twice daily will be required for symptomatic benefit in carcinoid diarrhoea.

Influence of H. pylori infection on gastric motor and sensory function in asymptomatic volunteers.

The effect of H. pylori infection on gastric motility and sensation is unclear. Our hypothesis is that H. pylori infection increases gastric sensation and reduces gastric accommodation and emptying. In eight H. pylori-positive and eight H. pylori-negative asymptomatic subjects, infection was proven by antral histology or culture. We evaluated: (1) gastric emptying of solids, (2) proximal gastric compliance, (3) fasting and postprandial proximal gastric tone and phasic contractions, (4) gastric sensation during balloon inflations or ingestion of cold water, and (5) abdominal vagal function. H. pylori infection was associated with lower gastric accommodation (median 75% postprandial increase in barostat balloon volume compared to fasting) when compared to the accommodation in uninfected volunteers (median 211% change from fasting). One H. pylori-positive subject had an abnormal abdominal vagal function test and her gastric accommodation response was reduced. Other motor and sensory functions in the two groups were similar. In asymptomatic volunteers, H. pylori infection and gastritis result in reduced accommodation (diastolic dysfunction) but no change in overall sensation or motor functions of the stomach.

Octreotide inhibition of flushing and colonic motor dysfunction in carcinoid syndrome.

OBJECTIVES: Previous studies showed increased plasma motilin and substance P concentrations and accelerated motor function in the small bowel and colon in patients with carcinoid diarrhea. Octreotide is beneficial in patients with carcinoid syndrome. Our hypothesis was that octreotide inhibits accelerated motility and gut neuropeptides in carcinoid syndrome. METHODS: In 12 patients with metastatic carcinoid syndrome, we investigated the effect of octreotide 50 microg s.c. t.i.d (n = 6) or placebo (n = 6) on postprandial symptoms, GI transit, colonic motility, and circulating levels of selected circulating peptides and amines. RESULTS: Octreotide reduced postprandial flushing (p = 0.03) but not pain. Octreotide significantly retarded overall colonic transit and proximal colonic emptying (p < 0.05); it tended to prolong small bowel transit time (p = 0.13) and to reduce postprandial colonic tone (p = 0.08) compared with placebo. Octreotide also reduced circulating levels of peptide YY, neurotensin, vasoactive intestinal polypeptide, and substance P but had no effect on plasma motilin, neuropeptide Y, calcitonin gene-related peptide, or histamine after meal ingestion. CONCLUSION: Octreotide ameliorates gut motor dysfunctions that characterize carcinoid diarrhea; the potential role of specific antagonism of serotonin, substance P, and vasoactive intestinal polypeptide alone or in combination with agents that inhibit their release in carcinoid diarrhea deserves further study.

Gastrointestinal sensation. Mechanisms and relation to functional gastrointestinal disorders.

This article reviews the basic anatomy and physiology of visceral afferent function and its application to a clearer understanding of visceral pain and symptoms in patients with functional gastrointestinal disorders. Recent investigations have focused on the potential role of visceral tone, different afferent (A delta and C) fibers, dorsal column neurons, and supraspinal modulation in the elicitation of visceral perception of noxious and nonnoxious stimuli arising in the gut. Greater understanding of these pathomechansims and their pharmacologic manipulation offers an opportunity for future therapeutic strategies for these disorders.

Relation between fat malabsorption and transit abnormalities in human carcinoid diarrhea.

BACKGROUND & AIMS: Fat and complex carbohydrates in the distal bowel activate "brakes" inhibiting upper gut motility. The hypothesis of this study was that rapid transit carcinoid diarrhea in association with steatorrhea results in impairment of gastric emptying. METHODS: Fifteen patients with carcinoid diarrhea without prior gastrointestinal resection or whose small bowel resection was limited to < 100 cm of ileum were studied. Gastrointestinal transit was measured scintigraphically with a standardized meal. Percentage of ingested fat excretion was calculated. RESULTS: Mean length of small bowel resected was 33 cm, and mean 24-hour urine 5-hydroxyindoleacetic acid was 120 mg. Fourteen patients had increased daily stool weights, and 10 had increased stool fat excretion (mean, 13%). Transit was accelerated in the small bowel in 14 and in the colon in all patients. The lag time for gastric emptying was prolonged in 2 patients who had no previous resection. Gastric emptying rate was accelerated in 5, normal in 7, and delayed in 3 patients. CONCLUSIONS: Ileal and colonic brakes do not seem to delay gastric emptying in patients with carcinoid diarrhea associated with rapid transit and mild to moderate steatorrhea.

Mechanism of accelerated gastric emptying of liquids and hyperglycemia in patients with type II diabetes mellitus.

BACKGROUND & AIMS: The roles of hyperglycemia in diabetic gastroparesis and gastric delivery in postprandial hyperglycemia of diabetic patients are unclear. The aims of this study were to assess gastric emptying and its relation to postprandial glucose metabolism in patients with asymptomatic non-insulin-dependent diabetes mellitus (NIDDM) and no autonomic neuropathy and to identify motor mechanisms responsible for any accelerated gastric emptying. METHODS: Autonomic function, gastric emptying, postprandial glucose metabolism, and hormone levels (glucagon, insulin, cholecystokinin, glucose-dependent insulinotropic polypeptide, neurotensin, and peptide YY) were assessed in healthy volunteers and patients with NIDDM. In a second study, gastric tone and motility were measured in patients with accelerated gastric emptying and in controls. RESULTS: Gastric emptying of solids did not differ in the two groups, but liquids emptied faster in patients with NIDDM (P < 0.02). The rate of entry of ingested glucose into the systemic circulation was similar, but higher postprandial glucagon and lower insulin concentrations led to greater (P < 0.01) postprandial hepatic glucose release. Levels of other enteropeptides, gastric accommodation, and antral motility were similar, but patients with NIDDM had greater proximal gastric phasic contractions than controls (P < 0.05). CONCLUSIONS: Excessive hepatic glucose release, not rapid entry of ingested glucose, is the primary cause of postprandial hyperglycemia in patients with NIDDM. Accelerated gastric emptying in patients with nonneuropathic NIDDM is associated with increased proximal stomach phasic contractions.