gastrins and Scleroderma--Systemic

The effects of famotidine on human upper gastrointestinal motility were investigated, together with the relationship of gastric alkalinization and serum gastrin levels to changes produced by famotidine. Intravenous famotidine (20 mg), at a dose level in which an inhibitory effect on acetylcholinesterase activity is not recognized, was given to 13 patients with progressive systemic sclerosis but no other disorders. Gastric phasic motor activity was not changed significantly, but the lower esophageal sphincter pressure was elevated significantly in comparison with 15 controls given physiological saline, even when gastric phasic motor activity was taken into consideration. Gastric alkalinization with 7% sodium bicarbonate did not significantly increase the sphincter pressure in all 7 subjects so treated. No significant correlation was recognized between the serum gastrin level, the lower esophageal sphincter pressure, and the gastric motility index in any of the 3 groups. It was, therefore, concluded that intravenous administration of famotidine affected upper gastrointestinal motility, especially the lower esophageal sphincter pressure, through an as yet unknown mechanism other than inhibition of acetylcholinesterase activity, gastric alkalinization, or elevation of serum gastrin levels.

Topics: Adult; Bicarbonates; Chi-Square Distribution; Famotidine; Female; Gastrins; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Scleroderma, Systemic; Sodium; Sodium Bicarbonate; Stomach

Gastrointestinal tract (GIT) is the most common organ system involved in systemic sclerosis (SSc). GIT involvement is mainly attributed to GIT dismobility and wide mouth diverticular. GIT involvement in SSc can be also severely debilitating and even life threatening. To our knowledge, the presence of gastrointestinal bleeding due to the presence of multiple peptic ulcers in scleroderma patients is not well described. In this case report, we describe a scleroderma patient with recurrent gastrointestinal bleeding due to multiple peptic ulcers, in which vagotomy, pyloroplasty, and cholocystectomy were performed and subcutaneous somatostatin was administered to discontinue the recurrent bleeding and stabilize her clinical condition.

Topics: Female; Gastrins; Hormones; Humans; Injections, Subcutaneous; Middle Aged; Peptic Ulcer; Peptic Ulcer Hemorrhage; Scleroderma, Systemic; Somatostatin

Hypochlorhydria, hypergastrinaemia, inflammation and Helicobacter pylori infection, dose and duration of omeprazole treatment may separately, or in combination, influence the proliferation of enterochromaffin-like (ECL) cells and parietal cell changes in gastric mucosa. To assess the effects of these variables comparisons were carried out in patients with the acid related Zollinger-Ellison syndrome (ZES) versus patients with progressive systemic sclerosis (PSS) and gastro-oesophageal reflux disease.. Twenty-five patients with PSS and 16 patients with ZES were included and received continuous omeprazole treatment for a mean of 7.5 and 9 years. The patients were investigated every 6-12 months with endoscopy, biopsies and histology, and plasma gastrin measurements. PSS patients were titrated by 24 h pH-metry to oesophageal pH>4, and all ZES patients were titrated to a basal acid output of zero H+.. Changes towards diffuse and linear ECL cell hyperplasia were observed in 41% of the PSS patients. Micronodular hyperplasia and neoplasia were not seen. In the ZES patients changes towards linear and micronodular hyperplasia were observed in all patients. Two patients developed ECL cell carcinoids; one of these had MEN-1 syndrome. Also parietal cell changes were more pronounced in the ZES group than in the PSS group.. In patients without intrinsic acid hypersecretion and hypergastrinaemia significant proliferation of ECL cells is not an issue irrespective of gastric mucosal inflammation, omeprazole dose, duration of treatment and acid inhibition. The level of gastrin secretion and high plasma gastrin appear to accelerate ECL cell proliferation and parietal cell changes possibly influenced by chronic gastritis and H. pylori infection.

Topics: Achlorhydria; Aged; Aged, 80 and over; Anti-Ulcer Agents; Cell Division; Drug Administration Schedule; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Neurosecretory Systems; Omeprazole; Parietal Cells, Gastric; Scleroderma, Systemic; Zollinger-Ellison Syndrome

Gastrointestinal involvement commonly occurs in systemic sclerosis (SSc), but its pathogenesis is not well understood. Since there is evidence of a defect in neurotransmitter release, we were interested in examining the relationship between gastrointestinal dysfunction and plasma concentrations of gastrointestinal regulatory peptides in patients with SSc. We studied 43 consecutive patients, 18 with diffuse and 25 with limited cutaneous disease.. Levels of corticotropin-releasing hormone (CRH), gastrin, motilin, neuropeptide Y (NPY), and peptide YY (PYY) were determined by radioimmunoassay and high-performance liquid chromatography (HPLC).. Plasma concentrations of CRH, motilin, NPY, and PYY were significantly increased among SSc patients compared with healthy control subjects, and HPLC-characterization of motilin, NPY, and PYY showed a different pattern of fragments. No correlation was found between esophageal hypomotility and the concentration of peptide. Acid output did not correlate with gastrin levels, but was more often increased in patients with increased CRH and NPY values. Fat malabsorption, assessed by the triolein breath test, was more common among patients with increased motilin and PYY.. This study shows that elevated peptide concentrations commonly occur in patients with SSc. Since regulatory peptides are involved in gastrointestinal motility, secretion, and absorption, further characterization of this neuroendocrine system may help in understanding the complex regulation of gastrointestinal dysfunction in SSc.

Topics: Adult; Aged; Corticotropin-Releasing Hormone; Female; Gastrins; Gastrointestinal Diseases; Humans; Male; Middle Aged; Motilin; Neuropeptides; Scleroderma, Systemic

Topics: Adult; Aged; Dietary Proteins; Fasting; Gastrins; Humans; Middle Aged; Scleroderma, Systemic

We examined 51 sera from patients with pernicious anaemia for their capacity to block maximal gastrin stimulation of acid secretion by isolated rodent gastric parietal cells. 14C-aminopyrine accumulation was used as the index of acid secretion in vitro. Sera from patients with pernicious anaemia gave significantly (P less than 0.005) more block of maximal gastrin stimulation of acid secretion (61.7 +/- 37.8%) than sera from 10 patients with systemic lupus erythematosus (19.6 +/- 17.7%), 10 with scleroderma (34.2 +/- 22.3%), five with rheumatoid arthritis (22.4 +/- 15.6%) or 30 from healthy persons (27.4 +/- 12.8%). Maximal histamine stimulation of acid secretion was not inhibited. The blocking factor was present in serum IgG fractions, and serum and IgG fractions gave parallel dose-response and dilution curves. The serum block was abolished by absorption with gastric mucosal cells and correlated with the presence of parietal cell surface autoantibody. We conclude that serum immunoglobulin in pernicious anaemia can block gastrin stimulation of acid secretion and suggest that this block may be mediated by competition with gastrin for surface receptors on parietal cells.

Topics: Adult; Aged; Aminopyrine; Anemia, Pernicious; Animals; Arthritis, Rheumatoid; Autoantibodies; Binding, Competitive; Dose-Response Relationship, Immunologic; Female; Gastric Acid; Gastrins; Humans; Immunoglobulin G; In Vitro Techniques; Intrinsic Factor; Lupus Erythematosus, Systemic; Male; Middle Aged; Parietal Cells, Gastric; Rats; Rats, Inbred Strains; Scleroderma, Systemic

Topics: Adolescent; Adult; Aged; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Scleroderma, Systemic

Topics: Bed Rest; Brain Stem; Diabetes Complications; Duodenal Ulcer; Gastrins; Gastroesophageal Reflux; Hernia, Diaphragmatic; Hernia, Hiatal; Humans; Scleroderma, Systemic

To determine the pathogenesis of esophageal dysfunction in scleroderma and Raynaud's disease, the lower esophageal sphincter (LES) was tested with: (a) methacholine acting directly at the cholinergic receptor on the muscle; (b) edrophonium, a cholinesterase inhibitor, enhancing the effect of released acetylcholine; and (c) gastrin I, acting through the release of acetylcholine. 10 patients with Raynaud's disease and 22 patients with scleroderma were compared with 20 normals and 20 patients with isolated LES incompetence. The mean basal LES pressure in normals was significantly greater than that recorded in both patients with scleroderma and Raynaud's disease. Six patients having scleroderma with normal peristalsis had an LES pressure significantly greater than that noted in 16 patients having scleroderma with abnormal peristalsis. In all groups, the per cent increase in LES pressure was similar when tested by direct muscle stimulation by methacholine. The response to agents that acted indirectly through intact cholinergic nerves differed in these groups. The LES response to gastrin I distinguished patients with normal peristalsis from those with abnormal peristalsis. The patients with normal peristalsis, either with scleroderma or with Raynaud's disease showed only a partial reduction in their response to gastrin I. The response to gastrin I was markedly reduced only in patients with abnormal peristalsis. These data indicate that in patients with scleroderma and Raynaud's disease, the LES response to direct muscle stimulation by methacholine was intact while the response to gastrin I and edrophonium was diminished.

Topics: Adult; Edrophonium; Esophageal Diseases; Esophagus; Gastrins; Humans; Manometry; Methacholine Compounds; Middle Aged; Raynaud Disease; Scleroderma, Systemic