motilin and Scleroderma--Systemic

Impaired gastric slow waves, frequent gastrointestinal (GI) symptoms and altered GI peptides have been reported in Scleroderma (SSc) patients. The aim of this study was to investigate the associations among these three important components in GI dysmotility. Seventeen fasted SSc patients underwent four channel surface electrogastrography, measuring % of normal gastric slow waves or dysrhythmia. Patients completed a questionnaire designed by us to assess demographics, upper and lower GI symptoms (symptom presence, frequency and impact on quality of life, QOL), by YES/NO, Likert Scales and Visual Analogue Scales 1-100 mm (called GI Dysmotility Questionnaire, GIDQ) and health-related QOL by SF-36. Fasting plasma vasoactive intestinal peptide (VIP) and motilin levels were measured by peptide immunoassays. There were significant correlations between percentages of gastric dysrhythmias (bradygastria or arrhythmia) and a number of major GI symptoms such as nausea, abdominal bloating and pain. The plasma level of VIP was correlated positively with % dysrhythmia but negatively with % normal slow waves. Motilin was positively correlated with slow wave coupling (coordination). No major differences were noted in the measured peptides or gastric slow waves between limited SSc and diffuse SSc. Correlations were noted between SF-36 domain scores and our GIDQ scores. In SSc patients, gastric dysrhythmias are correlated with certain GI symptoms. Correlations are also noted between plasma VIP/Motilin levels and gastric slow waves. Thus in SSc, gastric dysrhythmias may be predictive of development of certain dyspeptic symptoms. Plasma VIP may be involved in the development of dysrhythmias.

Topics: Adult; Disease Progression; Electromyography; Electrophysiology; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Motilin; Nausea; Peptides; Scleroderma, Systemic; Skin; Stomach; Surveys and Questionnaires; Vasoactive Intestinal Peptide

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.. 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.. 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.. 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.

Topics: Adult; Aged; Cholecystokinin; Colon; Esophageal Motility Disorders; Female; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Intestinal Pseudo-Obstruction; Intestine, Small; Male; Manometry; Middle Aged; Motilin; Octreotide; Peptide YY; Radiography; Radioimmunoassay; Scleroderma, Systemic; Severity of Illness Index; Somatostatin

Scleroderma patients frequently present esophageal and gastric emptying abnormalities and small bowel dysfunction. Erythromycin, a macrolide antibiotic, has been found to accelerate gastric and gallbladder emptying in both healthy subjects and diabetic patients. Our objective was to investigate the effects of 4-wk oral erythromycin administration on the gastric and gallbladder emptying, gastrointestinal symptoms (early satiety, abdominal pain, nausea, bloating, vomiting, and constipation), and motilin plasma levels of patients with scleroderma.. 12 scleroderma patients were investigated before and after 4-wk treatment with 250 mg oral erythromycin three times a day. The effect of a single i.v. dose of 2 mg/kg/h erythromycin on gastric and gallbladder emptying before starting the oral treatment was also evaluated. Gastric and gallbladder emptying after a solid meal were evaluated by sonography.. Single i.v. administration of erythromycin before the meal reduced gastric emptying T1/2 from 121.3 +/- 14.0 to 45.5 +/- 7.3 min (p < 0.01) and accelerated gallbladder emptying without affecting the peak. Four-week oral administration of erythromycin reduced gastric emptying T1/2 from 121.3 +/- 14.0 min to 46.5 +/- 8.3 min (p < 0.01). Peak gallbladder emptying was also significantly accelerated, while total emptying remained unchanged (p < 0.01). Furthermore, 4-wk erythromycin administration reduced both motilin plasma levels (from 223.4 +/- 53.8 to 145.4 +/- 67.2 pmol/L, p < 0.01) and symptoms of nausea, vomiting, and abdominal pain (p < 0.01), and increased bowel movements in a subset of scleroderma patients with intestinal pseudo-obstruction.. Erythromycin stimulates gastrointestinal motility in patients with scleroderma. Administered medium-term, it accelerates gastric and gallbladder emptying and alleviates gastrointestinal symptoms.

Topics: Drug Administration Schedule; Erythromycin; Female; Gallbladder Emptying; Gastric Emptying; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Male; Middle Aged; Motilin; Scleroderma, Systemic; Stimulation, Chemical; Time Factors

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

Patients with scleroderma may have abnormal motility of the small intestine, with pseudoobstruction and bacterial overgrowth. Standard stimulatory agents are often ineffective in such patients. Because the somatostatin analogue octreotide evokes intestinal motor activity in normal subjects, we hypothesized that it might increase motility in patients with scleroderma.. We studied the effects of octreotide on intestinal motility and plasma motilin concentrations in five fasting patients with scleroderma who had bacterial overgrowth and in six fasting normal subjects. The motor effects of octreotide were correlated with its effects on abdominal symptoms and bacterial overgrowth as determined by the level of breath hydrogen excretion.. In the normal subjects, octreotide (10 micrograms subcutaneously) increased the mean (+/- SD) frequency of intestinal migrating complexes, which reflect intestinal motility, from 1.5 +/- 1.0 to 4.1 +/- 1.1 every three hours. In the patients with scleroderma, who had no spontaneous migrating complexes, octreotide (100 micrograms) induced 3.6 +/- 2.3 complexes every three hours. These complexes propagated at the same velocity and had two-thirds the amplitude of the spontaneous complexes in normal subjects. Plasma motilin concentrations, which were higher in the patients with scleroderma (229 +/- 74 pmol per liter) than in the normal subjects (112 +/- 37 pmol per liter), were inhibited by octreotide, suggesting that intestinal activity evoked by octreotide is independent of motilin. Treatment of the patients with scleroderma with octreotide (50 micrograms every evening) for three weeks reduced breath hydrogen excretion while they were fasting from 25 +/- 5 to 4 +/- 2 ppm (P = 0.001) and breath hydrogen excretion after they ingested 50 g of glucose from 46 +/- 24 to 8 +/- 7 ppm (P = 0.015); these reductions were accompanied by a significant decrease in nausea, bloating, and abdominal pain and by less frequent emesis.. Octreotide stimulates intestinal motility in normal subjects and in patients with scleroderma. In such patients, the short-term administration of octreotide reduces bacterial overgrowth and improves abdominal symptoms. This agent may be useful for the treatment of intestinal dysmotility in patients with scleroderma.

Topics: Adult; Aged; Breath Tests; Duodenum; Female; Gastrointestinal Motility; Humans; Hydrogen; Intestine, Small; Male; Manometry; Middle Aged; Motilin; Octreotide; Scleroderma, Systemic; Stimulation, Chemical

Cyclic pattern of interdigestive motility and of plasma levels of motilin, somatostatin and pancreatic peptide (PP) show close relationship. During interdigestive state gastric and lower esophageal motility seems to be mediated by pulsatile release of motilin, whereas the motor activity of duodenum seems to be controlled by somatostatin. Disturbed interdigestive motility could be demonstrated in gastrointestinal diseases like bacterial overgrowth, sclerodermia, post-vagotomy diarrhea and reflux esophagitis.

Topics: Diarrhea; Female; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Intestinal Obstruction; Intestinal Secretions; Male; Motilin; Peptides; Scleroderma, Systemic; Somatostatin; Vagotomy

Fasting antral, duodenal, and jejunal motor activity and plasma motilin and pancreatic polypeptide were studied in 14 patients with systemic sclerosis, 6 and 9 without clinical evidence of small bowel involvement, and 8 healthy control subjects. Normal interdigestive motor activity was present in control subjects and patients without intestinal involvement. However, cyclic motor activity was absent in 3 of the patients with intestinal disease and the motility index per interdigestive cycle (or per 6-h recording period in those without cyclic activity) was significantly less in the antrum (181 +/- 103 mm2 compared with 760 +/- 86 and 1116 +/- 96 mm2 for patients without involvement and healthy control subjects, respectively), duodenum (153 +/- 101 mm2 compared with 1425 +2- 186 nd 1055 +/- 241 mm2), and jejunum (268 +/- 131 mm2 compared with 1166 +/- 97 and 1105 +/- 128 mm2). Metoclopramide and bethanechol significantly increased motor activity at the three sites in all subjects but the magnitude of the metoclopramide response was less in patients with intestinal involvement. Fasting concentrations of motilin and pancreatic polypeptide exhibited cyclic variation with peak values occurring during phase 3 of the interdigestive cycle. Plasma motilin during each phase of motor activity was significantly higher in patients with scleroderma, with or without intestinal involvement, than in control subjects. The abnormal motor activity demonstrated here indicates a possible mechanism by which intestinal stasis and bacterial overgrowth could occur and by which clinical disturbances of intestinal transit might arise.

Topics: Adult; Bethanechol; Bethanechol Compounds; Duodenum; Fasting; Female; Gastrointestinal Motility; Humans; Jejunum; Male; Metoclopramide; Middle Aged; Motilin; Motor Activity; Pancreatic Polypeptide; Pyloric Antrum; Scleroderma, Systemic