Gastrointestinal transit and gastric acid secretion in patients with achalasia

Previous studies suggest that patients with achalasia exhibit degenerative changes of extraesophageal nerve fibers. We investigated whether these morphological alterations are associated with functional abnormalities of the gastrointestinal tract. Patients with achalasia had a normal acid secretory response (5.5 +/- 1.5 mmol/hr) to vagal stimulation when compared to controls (6.0 +/- 5.3 mmol/hr). However, the half time of gastric emptying of liquids was significantly shorter in patients with achalasia (10.4 +/- 1.8 min) than in control subjects (19.3 +/- 11.3 min) (P less than 0.01). Although there was a tendency towards a more rapid gastrointestinal transit in patients with achalasia, these changes failed to reach statistical significance. It is concluded that patients with achalasia have a gastric emptying disorder that could either be explained by a selective defect of extraesophageal vagal inhibitory nerve fibers or as an epiphenomenon occurring as a consequence of impaired esophageal emptying.     

Influence of acid-pepsin secretion on gastric emptying of solids in humans: studies with cimetidine.

The commonly accepted model for gastric emptying suggests that the 'antral mill' is responsible for the triturition and subsequent emptying of solid food from the stomach. Little is known about the contribution to solid emptying made by other digestive mechanisms such as acid-pepsin secretion. We have investigated the effect of inhibiting gastic secretion on the rate at which a solid test meal emptied from the stomach. Using a radiolabelled beefburger, we performed paired gammacamera studies on consecutive days in 10 fasted, healthy volunteers to compare gastric emptying of the test meal with and without oral cimetidine (400 mg 1 hour before the test, 800 mg at the start of the meal). Inhibition of acid-pepsin secretion by cimetidine was associated with an appreciable delay in the rate of emptying of the burger from the stomach (T50 cimetidine 187 (16) min (mean (SEM); T50 no cimetidine 146 (15) min; p less than 0.01, paired t test). This delay was related to a change in the slope of the emptying profile and was not associated with a prolonged lag phase. These results may be explained by the relative achlorhydria and reduced pepsin activity induced by cimetidine impairing the breakdown of solid food into particles small enough to leave the stomach.     

Effect of long-term cimetidine on gastric acid secretion, serum gastrin, and gastric emptying.

Gastric acid secretion, gastric emptying, fasting serum gastrin and the serum gastrin response to a meal were measured in duodenal ulcer patients before, and at least five days after completing prolonged treatment with cimetidine (1 or 2 g/day for four or eight weeks followed by 600 mg twice daily for six months). Fasting serum gastrin and the gastrin response were also measured during treatment. Compared with pretreatment values, fasting serum gastrin concentrations were raised both during and five to 31 days after stopping treatment (P less than or equal to 0.02). The integrated gastrin response and the rate of gastric emptying of the solid component of the meal were increased during treatment (P less than 0.001 and P less than 0.002 respectively) but returned to pretreatment levels after stopping therapy. No significant changes were observed in the basal or maximal acid outputs or the rate of emptying of the liquid component of the meal. The results imply that the hypergastrinaemia associated with long-term cimetidine therapy does not result in increased gastric acid secretion.     

Gastric emptying of solids, acid secretion and tobacco in duodenal ulcer]

We study in a group of patients with endoscopically diagnosed duodenal ulcer (19; 17 males) and controls (11; 7 males) the gastric emptying of solids through scintigraphy and gastric acid secretion by standard tests. In the same way we investigated prospectively some clinical data, specially smoking habits. As a whole, patients with duodenal ulcer showed an emptying of solids slightly faster than controls (T 1/2-minutes-: 85.4 +/- 28.6 in patients with duodenal ulcer versus 116.9 +/- 46.5 in controls, p less than 0.03). However, most of our patients (15 of 19 or 79%) were found to have a normal emptying rate. No correlation was found between secretory outputs and gastric emptying. Smokers with duodenal ulcer had a faster emptying that non-smokers with duodenal ulcer (T 1/2 74.8 +/- 30.05 vs. 99.91 +/- 19.86; p = 0.05).     

Esophageal motility and gastric emptying in PSS patients, correlation with symptoms

Progressive systemic sclerosis (PSS) commonly involves the esophagus. Dysphagia and heartburn are the most common esophageal symptoms. In this study we evaluated the relationship between esophageal symptoms and esophago-gastric motility. On esophageal manometry, loss of peristalsis, peristaltic contraction amplitude of distal esophagus less than 30 mmHg and decreased LES pressure were critical for esophageal symptoms. The degree of symptoms correlated to esophageal dysmotility. The gastric emptying in PSS patients was delayed, but there was no significant difference in gastric emptying between the patients with and without reflux esophagitis. Esophageal dysmotility is considered to be much responsible for the reflux esophagitis in PSS patients than gastric emptying.     

Histological appearances of oesophagus, antrum and duodenum and their correlation with symptoms in patients with a duodenal ulcer.

Clinical data and histology from the oesophagus, gastric antrum, and duodenum were collected from 36 patients undergoing surgery for duodenal ulcer. Gastritis was present in 94% of the patients (25% of atrophic type), oesophagitis in 72% and duodenitis in 39%. Abnormal biopsies were present from all three sites in 33% of the patients. Only one patient showed three normal biopsies. The low incidence of duodenitis does not support the theory that duodenitis is part of the same spectrum as duodenal ulcer. Heartburn was related to the presence of gastritis (100%) and oesophagitis (76%) but not to duodenitis (52%). No relationship was found between the length of history, severity of pain, and histological abnormalities.     

Gastrin, gastric acid secretion, and gastric microflora in patients with rheumatoid arthritis.

The relation between the basal and stimulated gastric acid secretion, plasma gastrin, and the gastric microflora was examined in 45 patients with rheumatoid arthritis. Sixteen patients (36%) had basal achlorhydria, and of these, 10 (22%) had achlorhydria or hypochlorhydria after stimulation with pentagastrin. The peak acid output and acidity showed inverse correlation with the disease duration but were not associated with age or with the degree of physical disability. Hypergastrinaemia was found in nine patients (20%), of whom 6 (13%) had significant titres of parietal cell antibody. The acidity of the peak acid output showed negative correlation with plasma gastrin. It was confirmed that the gastric secretory state is a determinant of plasma gastrin levels and in addition influences the growth of micro-organisms in the gastric lumen. The type of microflora in the non-acid stomach was similar to that found in the saliva. A subgroup of eight females was identified who showed low gastric acid secretion rates, positive bacterial cultures, and atlantoaxial subluxation. Gastrin- and insulin-like immunoreactivities were found in joint fluid. The concentrations reflected their plasma levels, suggesting that the peptides are not released at the inflammatory site, but rather that they reach synovial fluid from circulating blood.     

Gastric acid secretion and gastric emptying of liquids in 99 male duodenal ulcer patients

Gastric acid hypersecretion and accelerated gastric emptying are commonly considered as possible determinants of duodenal ulcer, but the relative frequencies of these gastric dysfunctions have never been evaluated in a homogeneous group of patients. We studied basal and pentagastrin-stimulated gastric acid secretion and gastric emptying of a radiolabeled caloric liquid meal in 99 consecutive male patients with endoscopically proven, active, uncomplicated duodenal ulcers. Compared to matched healthy subjects, ulcer patients presented increased basal and stimulated acid secretion (P<0.001).Sixty-nine patients had peak acid output values above the 95% confidence limits of the control population (14.2–30.6 meq/hr).Cigarette smoking was correlated with gastric acid hypersecretion. No significant difference was found between duodenal ulcer patients and controls in mean gastric emptying times. Ulcer patients showed a greater variance of gastric acid secretion and emptying values than healthy subjects. This reflects varied gastrointestinal function among ulcer patients. No significant correlation was found between gastric acid output and gastric emptying times. These findings suggest that gastric acid hypersecretion, but not accelerated gastric emptying of liquids, play a relevant role in the pathogenesis of duodenal ulcer.     

Morphological and pharmacological studies of the parietal cells of the stomach in the dog during periods of maximal acid output and after the gastric secretory inhibitor UK-9040.

UK-9040, a derivative of the antihistamine triprolidine, is a potent gastric secretory inhibitor. Given orally to dogs it reduced gastric acid, pepsin and volume output in response to food, insulin, histamine, N-methyl histamine, and pentagastrin. Doses of 6-36 mg/kg administered orally four to five hours before the secretagogues produced a dose-dependant and up to 100% inhibition in the outputs of innervated gastric fistula and denervated Heidenhain pouch. Inhibition was still present 24 hours after administration of UK-9040 but was absent at 48 hours. Blood pressure and pulse rate were not affected. Studies with the electron microscope revealed that the normal ultrastructural responses to gastric secretory stimulation were arrested. UK-9040 showed no cumulative effect, tolerance did not occur, and after withdrawal of the drug the physiological and morphological gastric responses of the parietal cells rapidly returned to normal.     

Effect of endogenous pancreatic glucagon on gastric acid secretion in patients with duodenal ulcer before and after parietal cell vagotomy.

The effect of endogenous pancreatic glucagon on submaximal pentagastrin stimulated gastric acid secretion was studied by infusion of 1-arginine in patients with duodenal ulcer before and after parietal cell vagotomy without drainage (PCV). Preoperatively infusion of 1-arginine resulted in a marked inhibition of acid secretion, whereas no effect was found postoperatively. Plasma glucagon concentrations were identical pre- and postoperatively, fasting as well as during arginine infusion. Serum gastrin concentration rose after PCV but not unaffected by arginine infusion both pre- and postoperatively. The study demonstrates that intact vagal innervation of the fundic glands is a condition of inhibition of pentagastrin induced acid secretion by pancreatic glucagon released by infusion of 1-arginine.     

Total 24-hour gastric acid secretion in patients with duodenal ulcer. Comparison with normal subjects and effects of cimetidine and parietal cell vagotomy

The purposes of these studies were as follows: (a) to compare gastric acid secretion throughout an entire 24-h period in 8 patients with duodenal ulcer disease and in 7 normal subjects, and (b) to determine in duodenal ulcer patients to what extent total, 24-h acid secretion was reduced by oral cimetidine (n = 7) or parietal cell vagotomy (n = 7). Basal, interprandial, and nocturnal acid secretion were measured by gastric aspiration, whereas acid secretion in response to breakfast, lunch, and dinner was measured by in vivo intragastric titration. Total, 24-h acid secretion averaged 408.3 +/- 61.7 mmol in duodenal ulcer patients and 208.3 +/- 18.5 mmol in normal subjects (p less than 0.02). Acid secretion was higher in duodenal ulcer patients than in normal subjects during both day (p less than 0.01) and night (p less than 0.05). Cimetidine (400 mg twice daily) significantly (p less than 0.001) reduced total, 24-h acid secretion in duodenal ulcer patients to 235.3 +/- 58.6 mmol, a rate that was not significantly different from 24-h acid secretion in normal subjects. On the other hand, total, 24-h acid secretion averaged only 86.7 +/- 20.7 mmol after parietal cell vagotomy, a rate that was significantly lower than 24-h acid secretion in normal subjects (p less than 0.001) and in duodenal ulcer patients receiving cimetidine (p less than 0.05). These studies indicate that patients with duodenal ulcer disease secrete excessive amounts of gastric acid during the day and night and throughout an entire 24-h period. A twice-daily 400-mg dose of cimetidine reduces 24-h acid secretion in duodenal ulcer patients to nearly normal rates, whereas parietal cell vagotomy reduces acid secretion to well below normal rates.     

Neurotensin induced inhibition of gastric acid secretion in duodenal ulcer patients before and after parietal cell vagotomy

The influence of the vagal nerve on the inhibitory effect of neurotensin on pentagastrin stimulated gastric acid secretion was investigated in seven duodenal ulcer patients before and after parietal cell vagotomy without drainage. Preoperatively, neurotensin inhibited gastric acid secretion, whereas no effect was found postoperatively. Plasma concentration of neurotensin was identical pre-and postoperatively. This study shows that the inhibitory effect of neurotensin on gastric acid secretion is dependent on an intact vagal innervation of the parietal cell area.     

Effect of cisapride on gastric emptying of indigestible solids in patients with gastroparesis diabeticorum. A comparison with metoclopramide and placebo

Cisapride is a prokinetic agent believed to facilitate acetylcholine release from the myenteric plexus of the gut. The effect of cisapride on gastric emptying of solids was studied in 9 diabetic patients, all of whom had delayed gastric emptying of indigestible solids (gastroparesis). Six patients had chronic nausea and vomiting, and 3 had no symptoms. Cisapride (5 mg) was given intravenously 15 min before ingestion of a 400-kcal test meal and 10 indigestible solid radiopaque markers. On separate days and in random order each patient also received intravenous metoclopramide (10 mg) or placebo 15 min before ingestion of the meal and markers. Mean gastric emptying of radiopaque markers, assessed by serial radiographs of the gastric region, was accelerated by metoclopramide and cisapride, but the difference reached significance only with cisapride (p less than 0.05). There was considerable intersubject variability in gastric emptying responses to cisapride and metoclopramide. No side effects occurred with either drug. This study indicates that acute, intravenous administration of cisapride accelerates gastric emptying of indigestible solids in patients with diabetic gastroparesis.     

The endocrine polypeptide cells of the human stomach, duodenum, and jejunum

Thirty specimens of stomach, duodenum, and jejunum, removed at operation, were examined by optical microscopical, cytochemical, and electron microscopical techniques. The overall distribution of four types of endocrine polypeptide cell in the stomach, and three in the intestine, was determined. The seven cell types are described by names and letters belonging to a scheme for nomenclature agreed upon at the 1969 Wiesbaden conference on gastrointestinal hormones. The gastrin-secreting G cell was the only cell for which firm identification with a known hormone was possible. Although there was wide variation in the distribution of the various cells, from one case to another, striking differences were nevertheless observable, with respect to the G cell, between antra from carcinoma and from ulcer cases.