Effect of acute gastric electrical stimulation on the systemic release of hormones and plasma glucose in dogs.

This study evaluated the effect of gastric electrical stimulation (GES) with various parameters on plasma concentrations of satiety-related peptides and glucose. GES was performed in nine healthy dogs via electrodes implanted in the middle of the lesser curvature. Four sessions were performed in each animal: control, stimulation with IGS (implantable gastric stimulation for obesity, 0.3 m sec), modified IGS (2 msec), and long pulses (300 msec). Blood samples were collected at 15 and 0 min before the meal and at 15, 30, and 60 min after the meal. GES was initiated 30 min before the first blood sample and maintained throughout collection. Plasma ghrelin, leptin, insulin and glucose were measured. The total AUCs of plasma ghrelin and leptin were not significantly affected by GES. The total AUC of plasma insulin was significantly lower with IGS and long pulse parameters (P < 0.05). The total AUC for plasma glucose was significantly lower in sessions with long pulses and modified IGS parameters (P < 0.05). We conclude that acute GES is able to change the release of some satiety-related peptides. Whether this is associated with the changed eating behavior and weight loss in obese patients needs further investigation.

Giant hamartoma of the ascending colon in an adult with ulcerative colitis.

We report an unusual case of giant colonic hamartoma in a 50-yr-old man with ulcerative colitis. The clinical, endoscopic, and histological aspects of this case are discussed. In addition, the possible pathogenesis of colonic hamartoma is reviewed and related to our patient with ulcerative colitis.

Postresection hypergastrinemia correlates with malabsorption but not adaptation.

Massive intestinal resection is associated with transient hypergastrinemia and gastric hypersecretion. Gastric hypersecretion impairs intestinal absorption, but gastrin may be trophic during intestinal adaptation. Our aim was to determine if postresection hypergastrinemia correlates with malabsorption or adaptation. Ten dogs (13 to 19 kg) underwent 75% proximal intestinal resection. Intestinal remnant length and villus height was assessed at 12 weeks (n = 5) and 40 weeks (n = 5). Body weight and serum albumin, as well as stool fat, moisture, and weight, were measured preoperatively and at 4-week intervals for 40 weeks. Fasting serum gastrin values were measured by radioimmunoassay at similar intervals. Significant hypergastrinemia occurred between 4 and 28 weeks postresection. Hypergastrinemia did not correlate with increased intestinal remnant length (r = -.486, p = .407) or villus height (r = -.410, p = .584). Duration of hypergastrinemia (> 100 pg/ml) correlated with percentage of fecal fat at 12 weeks (r = .807, p = .015) and stool weight at 40 weeks (r = .881, p = .046). Thus, postresection hypergastrinemia correlates with early fat malabsorption and increased stool weight, but there is no correlation between hypergastrinemia and adaptation. These findings suggest that gastric hypersecretion, not hypergastrinemia, may be the more important pathophysiologic event after intestinal resection.

Somatostatin analogue inhibits intestinal regeneration.

Somatostatin analogue octreotide inhibits intestinal absorption and motility but its effect on epithelial cell migration and proliferation remains unclear. Our aim was to determine the effect of octreotide on parameters of intestinal regeneration, including epidermal growth factor (EGF)-induced changes. Thirty rabbits had full-thickness ileal defects patched with cecal serosa surface. Group 1 were controls. Groups 2 and 3 received 100 micrograms and 1000 micrograms, respectively, of subcutaneous octreotide daily. Group 4 received EGF at 1.5 micrograms/kg per hour via subcutaneous miniosmotic pump, and group 5 received both octreotide (1000 micrograms/d) and EGF (1.5 micrograms/kg per hour). Octreotide at 100 micrograms/d did not inhibit epithelial cell migration or proliferation at 7 days. Octreotide at 1000 micrograms/d inhibited normal but not EGF-stimulated cell migration. Octreotide decreased EGF-stimulated but not normal proliferation. Octreotide impairs epithelial cell migration in a dose-dependent manner. Octreotide inhibits EGF-stimulated proliferative activity but not EGF-stimulated migration. Prolonged administration of octreotide may adversely affect normal and adaptive intestinal regeneration by both direct and indirect effects.

gamma-Aminobutyric acid localization and function as modulator of cholinergic neurotransmission in rat antral mucosal/submucosal fragments.

gamma-Aminobutyric acid, a neurotransmitter in the central nervous system, has been shown to be present in and synthesized and secreted by rodent and feline myenteric plexus neurons. The aims of the present studies were to measure gamma-aminobutyric acid concentrations and synthesis and to establish cellular localization and uptake of gamma-aminobutyric acid by immunocytochemistry and autoradiography, respectively, within mucosal and submucosal tissues of the rat antrum. Direct demonstration of [3H]gamma-aminobutyric acid release and the effects of exogenous gamma-aminobutyric acid and muscimol, a GABA alpha agonist, on [3H]acetylcholine release from antral mucosal/submucosal fragments were examined in perifusion experiments. gamma-Aminobutyric acid content and synthesis, as reflected by glutamic acid decarboxylase activity, were present within antral mucosa at levels two to three times that of the body and muscular layers of both the gastric body and antrum. gamma-Aminobutyric acid was identified immunocytochemically, principally in mucosal epithelial cells of the antrum. Exogenous gamma-aminobutyric acid and muscimol were capable of stimulating acetylcholine release through a GABA alpha receptor-mediated mechanism that was abolished by tetrodotoxin. These results indicate that gamma-aminobutyric acid is present in and taken up by epithelial cells of the gastric antrum and that gamma-aminobutyric acid is capable of being synthesized by antral mucosal/submucosal tissues. Furthermore, these studies suggest that a peripheral gamma-aminobutyric acid mechanism that may modulate cholinergic neurotransmission and endocrine cell function exists within the antrum.

Cholecystokinin, vasoactive intestinal peptide and peptide histidine methionine responses to feeding in anorexia nervosa.

Anorexia nervosa (AN) is a syndrome of unknown cause characterized by voluntary starvation. Cholecystokinin has been implicated as a neuroendocrine regulatory factor in control of satiety. Relatively little information is known about gastrointestinal hormone responses to feeding in subjects with anorexia nervosa. In the present studies, we examine fasting and postprandial levels of cholecystokinin (CCK), vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in anorexia nervosa subjects and in control individuals. Results of these studies indicate that plasma CCK response to a liquid meal (Ensure Plus) in untreated AN subjects was distinctly different from that observed in healthy controls, both in terms of temporal pattern of peptide released and the amount of CCK secreted into the circulation. Peak levels of CCK release occurred at 30 min following meal ingestion in AN patients and at 60 min in control subjects. Integrated CCK release in untreated AN patients was approximately twice that measured in control individuals. Renutrition therapy was associated with reversion of the pattern of CCK release to that observed in control subjects. Plasma VIP levels were unchanged following meal ingestion in both control and anorexic subjects. In contrast, PHM levels in AN subjects were significantly greater than that observed in control individuals. The pattern of PHM release following liquid meal ingestion was similar to that observed with plasma CCK; namely, peak release of peptide was observed at 30 min which was significantly greater than corresponding control values (P less than 0.05). In conclusion, these results demonstrate distinctive differences in plasma CCK and PHM levels in response to feeding in AN subjects when compared to control individuals. These findings suggest that the earlier and greater rise in plasma CCK levels in AN subjects following meal ingestion may contribute to the abnormal sensation of satiety in this condition.

Endoscopy in the diagnosis of gastrointestinal Mycobacterium avium-intracellulare infection.

Two cases of mycobacterium avium-intracellulare (MAI) infection in association with acquired immunodeficiency syndrome (AIDS) are presented to highlight the distinctive upper gastrointestinal endoscopic appearances: 2 X 4 mm diameter, white nodules with intervening erythema and hemorrhagic erosions covered the mucosa of the second part of the duodenum. Histological evaluation of these nodules revealed diffuse expansion of the lamina propria by macrophages that contained numerous intracellular and extracellular acid-fast organisms. We conclude that endoscopy with endoscopic biopsy may represent the most rapid and sensitive diagnostic tool available in this disease.

Development of squamous cell carcinoma of the esophagus after endoscopic variceal sclerotherapy.

We describe the case of a 45-yr-old white male with portal hypertension and presumed Laennec's cirrhosis who developed squamous cell carcinoma of the esophagus 8 months after completion of a course of endoscopic variceal sclerotherapy. The epidemiology and natural history of esophageal cancer and their relationship to our patient are analyzed. This report emphasizes that squamous cell carcinoma of the esophagus should be considered in the differential diagnosis of postsclerotherapy dysphagia. Further studies will be required to determine whether or not esophageal variceal sclerotherapy is associated coincidently or causally with the development of squamous cell carcinoma of the esophagus in patients at increased risk for this condition.

Mechanisms of vasoactive intestinal peptide release in short-term culture of vasoactive intestinal peptide-producing tumor.

Vasoactive intestinal peptide-producing tumor tissue fragments obtained at surgery were maintained in short-term culture. Functional cellular integrity of vasoactive intestinal peptide-producing tumor tissue was reflected by progressive protein synthesis and the ability of tumor tissue to release vasoactive intestinal peptide when stimulated by the intracellular second messengers cyclic adenosine monophosphate and calcium. Studies with verapamil and ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetraacetic acid suggest that cyclic nucleotide- and ionophore A23187-mediated vasoactive intestinal peptide release are dependent, at least in part, upon the availability and transmembrane transport of extracellular calcium.

Antral release of gastrin and somatostatin in duodenal ulcer and control subjects.

Organ culture was used to compare gastrin and somatostatin release from cultured antral mucosa obtained from duodenal ulcer and non-ulcer (control) subjects. In response to dibutyryl cyclic AMP (DBCAMP) cultured antral mucosal explants from patients with a history of duodenal ulcer released a greater proportion of antral gastrin into the medium than did antral mucosal explants from non-ulcer subjects. Somatostatin release from antral mucosa from duodenal ulcer patients was substantially less than somatostatin released by antral explants from non-ulcer subjects. In the non-ulcer subjects there was a direct positive correlation between the amounts of antral somatostatin and gastrin released into the culture medium (r = 0.64, less than p 0.01). In the duodenal ulcer patients, however, there was no correlation between gastrin release and somatostatin release from antral mucosa ( r = 0.09; p greater than 0.2). Results of these studies identify enhanced gastrin release in response to stimulation and decreased release of somatostatin from antral mucosa of duodenal ulcer patients. These alterations in paracrine relationships of antral somatostatin and gastrin in duodenal ulcer subjects may contribute, at least in part, to the pathogenesis of duodenal ulcer disease.

Decision analysis in evaluation of hypergastrinemia.

Hypergastrinemia and gastric acid hypersecretion are the principal laboratory features of Zollinger-Ellison syndrome. Decision and cost-effectiveness analyses were employed in the present study to compare and contrast the diagnostic strategies of initial gastric analysis followed by secretin infusion test versus secretin infusion test alone in the evaluation of hypergastrinemia in patients suspected of having gastrinoma. The results of this study showed that 59 percent of patients with elevated serum gastrin values were either hypochlorhydric or achlorhydric. Application of decision analysis to either diagnostic strategy demonstrated that gastric analysis followed by secretin infusion test, if indicated, was superior in expected value than secretin infusion test alone. Likewise, in this group of patients, performance of gastric analysis in the outpatient setting prior to secretin infusion testing was financially more advantageous than performance of secretin infusion testing alone. These results also demonstrate the importance of performing gastric analysis prior to anticipated hospitalization for evaluation of suspected gastrinoma. Such testing would obviate unnecessary hospitalization and medical costs.

Postreceptor inhibition of antral gastrin release by somatostatin.

This study was performed to examine the effects of somatostatin on antral gastrin release stimulated by postreceptor increases in adenosine cyclic nucleotide. Increases in intracellular levels of cyclic adenosine monophosphate were achieved through the use of the dibutyryl derivative of cyclic adenosine monophosphate and the phosphodiesterase inhibitor theophylline. The effects of somatostatin on basal and stimulated gastrin release were examined in rat antral organ culture experiments. Inclusion of somatostatin in the culture medium (1 X 10(-8) to 1 X 10(-4) M) resulted in significant inhibition of gastrin release at somatostatin concentrations of 1 X 10(-5) and 1 X 10(-4) M: both doses of somatostatin inhibited gastrin release by approximately 52% at 30 min and by 32% at 6 h. Gastrin release stimulated by dibutyryl cyclic adenosine monophosphate was significantly inhibited by 1 X 10(-5) and 1 X 10(-4) M somatostatin to 133% and 121% at 30 min and 77% and 98% at 6 h, respectively. Gastrin release stimulated by theophylline (1 mM) was also significantly inhibited by somatostatin in doses ranging from 1 X 10(-6) to 1 X 10(-4) M. The degree of inhibition by somatostatin of dibutyryl cyclic adenosine monophosphate- and theophylline-stimulated gastrin release declined over the duration of culture. In conclusion, these results suggest that somatostatin inhibits adenosine cyclic nucleotide-stimulated gastrin release by acting at a point distal to the formation of cyclic adenosine monophosphate.

Invasive endometriosis of the terminal ileum: a cause of small bowel obstruction of obscure origin.

A 40-year-old woman with a five-month history of intermittent abdominal pain in the right lower quadrant, diarrhea, and signs of small bowel obstruction was thought to have Crohn's disease of the terminal ileum. At operation, endometriosis of the terminal ileum was found and treated by resection. Enteric endometriosis is a rare cause of small bowel obstruction and the correct diagnosis is usually made at surgery.

Sensitivity of single contrast barium enema with regard to colorectal disease as diagnosed by colonoscopy.

The results of single contrast barium enema were retrospectively correlated with colonoscopically diagnosed colorectal disease in 54 patients (75 lesions). Altogether 66 lesions (88%) were correctly diagnosed. The sensitivity of barium enema for polyps was 81% (26/32). There were three perceptive errors and three polyps 5 mm or less in size were not demonstrated by barium enema. Twenty-nine cases of inflammatory disorders were all correctly diagnosed. One of 12 malignancies was missed by perceptive error. In two cases with vascular malformations the barium enema was normal. 4/9 (44%) of missed lesions were perceptive errors and could have been probably avoided by a second independent reading of films.

Effects of cyclic adenosine and cyclic guanosine nucleotides and theophylline on gastrin synthesis and secretion in rat antral organ culture.

The effect of cyclic adenosine and cyclic guanosine nucleotides and theophylline upon gastrin synthesis and secretion were examined in rat antral mucosa maintained in organ culture. In concentration-response experiments, cyclic AMP, dibutyryl cyclic AMP and theophylline stimulated gastrin release and incorporation of [3H]-tryptophan into gastrin: a high degree of positive correlation was demonstrated between gastrin synthesis and gastrin release in response to control and test culture conditions. Cyclic GMP and dibutyryl cyclic GMP also stimulated gastrin secretion to a degree similar to that seen with cyclic AMP. These studies provide support for the proposal that the cyclic nucleotide system is involved in the stimulation of gastrin synthesis and release by the antral gastrin cell.

Role of calcium in antral gastrin release.

The role of calcium in gastrin release was investigated using rat antral organ culture. During the initial 4-h culture interval, in the absence of calcium in the culture medium, gastrin release was not different from that observed with 0.5, 1, and 2 mM calcium. However, after 6 h of culture, gastrin release with 0.5, 1, and 2 mM calcium was significantly greater than that with antral explants cultured in calcium-free media. In the presence of 1 mM calcium in the culture medium gastrin release was stimulated by dibutyryl cyclic AMP, whereas with calcium-free culture medium dibutyryl cyclic AMP was ineffective in stimulating gastrin release. Effects of ionophore A23187 on gastrin release were examined in experiments with culture medium containing no added calcium and with 2 mM calcium. The dose-response to ionophore A23187 (1.2--10 microgram/ml) with 2 mM calcium demonstrated progressive increases in culture media gastrin at 30, 60, and 120 min of culture. Maximal gastrin release occurred with 10 microgram/ml ionophore at each culture interval. Gastrin releases was not stimulated by increasing doses of ionophore when added to calcium-free organ culture media. Results of these experiments suggest that calcium is important in regulation of antral gastrin release and that dibutyryl cyclic AMP-stimulated release of antral gastrin is, at least in part, calcium-dependent. Stimulation of gastrin secretion by ionophore A23187 (in the presence of calcium) further supports the role of calcium in antral gastrin release and suggests that transport of calcium across cellular membranes is important in the coupling of secretory events in the gastrin cell.

The role of gastrin in duodenal ulcer.

It is now evident that hypersecretion of gastric hydrochloric acid is an important pathogenetic element among a variety of heterogeneous factors responsible for the production of common duodenal ulcer. Hypersecretion of gastric acid due to usually strikingly increased circulating levels of gastrin released from gastrinoma tissue is characteristics of patients with to Zollinger-Ellison Syndrome. In contrast, fasting serum gastrin levels are normal in patients with common duodenal ulcer. The polypeptide hormone, gastrin does, however, appear to play subtle and multiple roles in enhancement of gastric acid secretion in duodenal ulcer. Recent evidence suggests that abnormalities in gastrin release and action may be influenced by participation of somatostatin. The hypothesis is proposed for consideration and for further investigation that the multiple subtle abnormalities in gastrin release and parietal cell sensitivity to gastrin may be due to disturbances in the actions or concentrations of locally acting polypeptides, substances which are capable of suppressing gastrin release and its effects (somatostatin), or alternatively, are capable of stimulating release of gastrin into the circulation (bombesin).

Sclerosing peritonitis and propranolol.

Sclerosing peritonitis developed in a 43-year-old man with angina pectoris who had been receiving the beta-adrenergic receptor antagonist, propranolol. The patient had abdominal and back pain, weight loss, a midabdominal fullness, ascites, and evidence of partial small bowel obstruction. At surgery, the small bowel was distended and encased by dense fibrous tissue. Infectious and neoplastic causes of fibrosing peritoneal inflammation were excluded. The patient described in this report illustrates several features commonly experienced by individuals who developed sclerosing peritonitis associated with beta-adrenergic receptor blockade therapy. To my knowledge, the development of ascites and considerable ascitic fluid leukocytosis have not been described previously with this disorder.

Severe hyperchloremic acidosis complicating jejunoileal bypass.

In summary, severe hyperchloremic acidosis developed in two patients as a late complication after jejunoileal bypass for morbid obesity. This acidosis was associated with episodes of dizziness, ataxia, headache, weakness, confusion and transient loss of consciousness. Recognition of this symptom complex in the patient with a jejunoileal bypass should suggest metabolic acidosis as a complication of this surgical procedure. Bicarbonate replacement provided prompt, but temporary, improvement in the symptoms and the acidosis. Revision of the intestinal bypass was required for correction. Special studies to rule out renal tubular acidosis were performed and definitely excluded the kidney as a source of the acidosis.