Gastroesophageal Sphincter Pressure and Serum Gastrin: Reaction to Food Stimulation in Normal Subjects and in Patients with Gastric or Duodenal Ulcer

Gastroesophageal sphincter pressure and serum gastrin concentration were determined in the fasting state and after the intake of a protein food in 6 normal subjects, 6 patients with gastric ulcer, and in 6 patients with duodenal ulcer. No significant differences in the fasting state were found. After the food intake, gastroesophageal sphincter pressure increased significantly over basal values in normals and in patients with duodenal ulcer, but in patients with gastric ulcer a decrease in pressure was noted. Serum gastrin rose in all subjects studied after the food stimulation, but it was significant only in the gastric and duodenal ulcer group. In two normals and two patients with duodenal ulcer the ingestion of a potato meal of similar weight to that of the protein meal showed no change either in serum gastrin or in sphincter pressure. In one additional normal subject and one duodenal ulcer patient the constant intravenous infusion of Aminosol for 2 h produced no change in serum gastrin or sphincter pressure. These results indicate that the effect of protein food on sphincter pressure is different for gastric or duodenal ulcers, and, furthermore, that this effect is mediated by proteins in the gastrointestinal tract.     

Lysolecithin and Glyceroglucolipids in Gastric Secretion of Patients with Gastric and Duodenal Ulcer

Basal and pentagastrin-stimulated gastric secretions, collected (at 15-min intervals for 1 h) from six duodenal ulcer and six gastric ulcer patients, were analyzed for their content of lecithin, lysolecithin, and glyceroglucolipids. Whereas the glycero-glucolipid concentrations and the molar ratios of lysolecithin to lecithin (2.5:1) in basal and stimulated secretions from patients with duodenal and gastric ulcer were similar, significant (p < 0.01) differences were noted between these two groups with regard to the lysolecithin contents. The basal secretions of patients with duodenal ulcer contained about 4.5-fold less (204 μmol/l) of lysolecithin than those from patients with gastric ulcer (932 μmol/l). After pentagastrin stimulation, the lysolecithin concentrations in the secretion from duodenal ulcer patients rose slightly (to 212 μmol/l), whereas a twofold decrease (to 440 μmol/l) in lysolecithin was observed in the secretion from patients with gastric ulcer. Statistically significant correlation between concentrations of lysolecithin and glyceroglucolipids was only observed in basal (r = 0.85, p < 0.05) and stimulated (r = 0.93, p < 0.01) secretions from patients with gastric ulcer. It is concluded that high concentrations of lysolecithin in the secretion of gastric ulcer patients results in the weakening of the gastric mucosal barrier by depleting its glyceroglucolipid component.     

Effect of Ranitidine on the Content of Glyceroglucolipids in Gastric Secretion of Patients with Gastric and Duodenal Ulcer

The glyceroglucolipids content of basal and pentagastrin-stimulated gastric secretion was measured in male patients with gastric (12) and duodenal (12) ulcer. Six patients in each group received twice daily for a period of 4 weeks 150 mg of ranitidine, whereas the other patients received placebo. The glyceroglucolipids output in the basal secretion of patients with gastric and duodenal ulcer before treatment was similar and increased 2.7-fold after pentagastrin stimulation. In all patients treated with ranitidine, the mean output of glyceroglucolipids after pentagastrin stimulation increased from 1.38 to 2.05 μmol/h (P < 0.05). This increase, however, was more pronounced in the duodenal ulcer group than in the gastric ulcer patients. No change in glyceroglucolipids output was noted in the patients treated with placebo. The ratio of glyceroglucolipids to HCl increased significantly (P < 0.02) only in the ranitidine-treated patients.     

Gastric Acid Secretion and Duodenal Ulcer Healing during Treatment with Omeprazole

Twenty-seven duodenal ulcer patients were treated with omeprazole, 40 mg daily for 4 weeks. The peak acid output to pentagastrin measured 24 h after dosing was reduced by 54% on day 3 of the study and by 74% on day 14. The ulcers in 25 of 26 patients had healed by the end of the treatment period, and 1 patient was unable to attend the final endoscopy. Ulcer symptoms were relieved rapidly. The drug was well tolerated, and few adverse reactions were reported.     

Pancreatic and Gastric Secretion in Rats Studied by Means of Duodenal and Gastric Perfusion

The duodenum and stomach of female rats, anaesthetized by urethane, were perfused separately and continuously with saline solution. Stimulation was performed by means of intravenous infusion of secretin, cholecystokinin-pancreozymin (CCK-PZ), and pentagastrin in a ‘step-test’, increasing the infused dosages in 20-minute periods. During basal secretion only acid and bicarbonate were detectable. High amounts of CCK-PZ induced the same maximal acid output as pentagastrin. All three hormones evoked the bicarbonate output in different intensities. The output of pancreatic enzymes was influenced only by CCK-PZ and pentagastrin. During the course of stimulation amylase showed a constant secretion rate. On the other hand, trypsin and chymotrypsin output increased to a peak and then decreased. In contrast to man and the dog, rather high doses of the different hormones are necessary to reach maximal secretion of acid, bicarbonate, and enzymes.     

Cholecystokinin in the Control of Gastric Acid Secretion and Gastrin Release in Response to a Meal at Low and High pH in Healthy Subjects and Duodenal Ulcer Patients

Objective: In healthy subjects a gastric meal at low pH inhibits gastric acid secretion, possibly by reducing gastrin release, whereas duodenal ulcer (DU) patients have been reported to show a lack of this low pH inhibition of gastric secretion.

Methods: The intragastric pH profiles were measured in seven healthy subjects and seven DU patients after meals of pH6.5 and 3.0 without or with pretreatment with loxiglumide (1.2 g orally), a selective antagonist of type-A cholecystokinin (CCK) receptors. During all tests (30min before and 30, 60, and 90min after each meal) plasma gastrin, CCK, and somatostatin were determined by specific radioimmunoassays.

Results: In healthy subjects a standard meal at pH 6.5 and 3.0 resulted in median 3-h intragastric pH of 3.8 and 2.8, respectively. In DU patients under the same conditions the pH6.5 meal resulted in median 3-h intragastric pH of 3.4, and the acidified meal in pH 2.2. After pretreatment with loxiglumide the median pH after both meals was significantly lower in healthy controls but not in DU patients. After the pH 6.5 meal, in healthy subjects the plasma gastrin rose by 57%. CCK by 177%. and somatostatin by 39%, and in DU patients by 152%, 367%, and 125%, respectively. Pretreatment with loxiglumide led to a marked increase in plasma gastrin response to the pH 6.5 meal only in healthy controls and not in DU subjects, and it was accompanied by a significant increase in plasma CCK and a decrease in plasma somatostatin. The pH 3.0 meal resulted in a significantly smaller rise in plasma gastrin and a higher increase in CCK and somatostatin in both groups; again, after treatment with loxiglurnide only healthy controls and not DU patients showed significant increase in plasma gastrin level.

Conclusions: Acidification of meals results in the reduction of plasma gastrin and increase in plasma CCK and somatostatin in both healthy subjects and DU patients. DU patients differ from healthy subjects by virtually unchanged plasma gastrin response to a meal after CCK antagonism with loxiglumide, suggesting a defect in both gastric acid and gastrin inhibition by CCK in these patients.     

Gastric Acid Secretion,Serum Pepsinogen I,and Serum Gastrin in Japanese with Gastric Hyperplastic Polyps or Polypoid-Type Early Gastric Carcinoma

We determined the maximum secretion of gastric acid and the fasting serum levels of pepsinogen I and gastrin in Japanese patients with gastric hyperplastic polyps or polypoid-type early gastric carcinoma, comparing those findings with observations in control subjects. Both the maximum acid secretion and fasting levels of serum pepsinogen I were significantly lower in the patients with gastric hyperplastic polyps or polypoid-type early gastric carcinoma than in the controls. Fasting serum gastrin levels were significantly higher in the patients with gastric hyperplastic polyps than in the other two groups of subjects. These data demonstrated that the combination of hypochlorhydria, a low level of pepsinogen I, and hypergastrinemia (type-A gastritis) was common in the patients with gastric hyperplastic polyps, whereas hypochlorhydria and a low pepsinogen I without hypergastrinemia (type-B gastritis) were common in those with polypoid-type early gastric carcinoma.     

Response of Heidenhain Pouch to Histamine,Gastrin and Feeding before and after Truncal Vagotomy in Dogs

Dogs with both gastric fistulas of the main stomach and Heidenhain pouches were studied before and after transthoracic truncal vagotomy. Confirming earlier studies in dogs with gastric fistulas alone, truncal vagotomy abolished the acid secretion in response to 2-deoxy-D-glucose (2-DG) and depressed the response to submaximal doses of exogenous gastrin or histamine but did not alter the maximal responses to gastrin or histamine. Effects of truncal vagotomy on acid secretion from the Heidenhain pouches: a) response to 2-DG with the gastric fistulas open was abolished, b) submaximal, but not maximal, responses to histamine were decreased, c) submaximal and maximal responses to exogenous gastrin were markedly increased, and d) response to feeding was markedly increased.     

Gastric Acid Response to Sham Feeding and Pentagastrin before and after Parietal Cell Vagotomy in Patients with Duodenal Ulcer

The influence of sham feeding (PAO_Sh) preceding pentagastrin-stimulated gastric acid secretion (PAO_Pg) was investigated in 28 patients with duodenal ulcer (DU) before vagotomy and in 36 after parietal cell vagotomy (PCV). Sham feeding had little influence on PAO_Pg and it is concluded that the two secretion tests may be combined. The ratio PAO_Sh/PAO_Pg was significantly reduced by PCV. Fourty-four patients with DU were studied for 1 year after PCV. and their PAO_Pg was measured preoperatively and their PAO_Pg and PAO_Sh postoperatively. Seven of the 44 patients had recurrent ulcer within 1 year. PAO_Pg had no predictive value pre- and postoperatively, but postoperative PAO_Sh and PAO_Sh/PAO_Pg were both significantly higher in patients with recurrent ulcer. It is concluded that PAO_Sh and PAO_Sh/PAO_Pg after PCV may assess completeness of vagotomy, but the relationship between PAO_Sh and risk of recurrent ulcer may be stronger than that between PAO_Sh/PAO_Pg and recurrence.     

Gastric Acid Secretion and Pattern of Gastroesophageal Reflux in Patients with Esophagitis and Concomitant Duodenal Ulcer: A Multivariate Analysis of Pathogenetic Factors

This study was designed to assess the relationship between gastric acid output (GAO) and both pattern of gastroesophageal reflux (GER) and severity of esophageal lesions. Gastric acid secretory testing and 24-h intraesophageal pH-monitoring were performed in 31 patients with esophagitis and concomitant duodenal ulcer (E + DU) and compared with those of 72 patients with esophagitis (E). The second aim of this study was to evaluate the role of GAO and other potential pathogenetic factors in the development of esophagitis. The results of the study showed that GAO in patients with E + DU was significantly higher than in patients with E (p < 0.05). There was no significant difference between the two groups of patients with regard to endoscopic findings or GER variables (p > 0.05). Multiple regression analysis with stepwise deletion showed that the presence of hiatal hernia, GER in the upright position and age appear to correlate significantly with the presence of esophagitis. We conclude that no parallel relationship exists between GAO and severity of GER or esophageal lesions in patients with E + DU and that GAO is not a major pathogenetic factor in GER disease.     

Effect of a 28-Day Therapy with Famotidine on Blood Levels of Alcohol and Gastrin and Intragastric pH in Healthy Human Subjects

Teyssen S, Chari ST, Joos A, Singer MV. Effect of a 28-day therapy with famotidine on blood alcohol and gastrin and intragastric pH in healthy human subjects. Scand J Gastroenterol 1994;29:398-405.

In a randomized, placebo-controlled study of 10 healthy human subjects blood alcohol levels after consumption of beer. 24-h intragastric pH, and serum gastrin concentrations were serially measured during a 28-day therapy with famotidine. The subjects consumed placebo or famotidine (40 mg at 1830 h) and beer (500 ml at 1900 h) every day for 28 days. On days 1, 7, and 28 of the study 24-h intragastric pH-metry and blood alcohol and gastrin estimations were performed. Famotidine did not significantly alter either the peak or the 2-h integrated blood alcohol response to beer. The median intragastric pH on days 1, 7. and 28 was significantly (p < 0.006) increased by famotidine. After 7 days of famotidine therapy, however, the pH was significantly (p < 0.03) lower than on day 1 (4.0 versus 2.4); this effect persisted on day 28 (2.3). Whereas basal plasma levels of gastrin were not significantly altered by famotidine, the 2-h integrated plasma gastrin response to beer was significantly (p < 0.05) higher with famotidine than with placebo. We conclude that 1) a 28-day therapy with famotidine does not alter blood alcohol levels in response to social consumption of beer; 2) after 7 days of therapy tolerance to its gastric acid-inhibitory effect is seen; and 3) an exaggerated postprandial release of gastrin may be involved in the development of this tolerance.     

Effect of Cimetidine on Histamine- and Pentagastrin-stimulated Gastric Secretion in Healthy Subjects

Cimetidine-induced inhibition of gastric acid and pepsin secretion in response to histamine and pentagastrin stimulation was studied in four healthy young subjects. Different doses of histamine and pentagastrin were administered alone and in combination with cimetidine on separate days; the order of administration was randomized. As the dose of histamine increased, the inhibitory effect of 0.6 mg · kg^?1 h^?1 of cimetidine on acid output decreased. With supramaximal histamine stimulation the inhibition was completely overcome. These results are consistent with competitive inhibition of histamine-stimulated acid output by cimetidine in man. After pentagastrin stimulation the inhibition of acid output by cimetidine could not be overcome by increasing the dose of the stimulant, suggesting a noncompetitive inhibition of pentagastrin-evoked acid output. It is concluded that the kinetics of cimetidine-induced inhibition of histamine- and pentastrin-stimulated gastric acid output are different. At approximately half maximal stimulation of acid secretion, cimetidine was a more potent inhibitor of histamine than of pentagastrin. Pepsin output in response to both histamine and pentagastrin stimulation was also inhibited by cimetidine.     

Gastric Emptying and Dyspeptic Symptoms in Patients with Nonautoimmune Fundic Atrophic Gastritis

Our aim was to evaluate the relationship between gastric emptying and demographic, clinical, histological, and secretory features in patients with nonautoimmune fundic atrophic gastritis. Only 31% of 45 patients with fundic atrophic gastritis presented with achlorhydria. Scintigraphic gastric emptying of solids was delayed compared to healthy controls. Patients with achlorhydria showed gastric emptying rates lower than those with preserved acid secretion. Significant, but weak, correlations were observed between emptying rates and both peak acid output (Rs = 0.33) and serum gastrin levels (Rs = –0.36), but not with grading of mucosal atrophy. No symptom differences were observed between patients with or without achlorhydria, but a weak correlation was detected between peak acid output and the severity of epigastric pain (Rs = 0.40). In conclusion, patients with fundic atrophic gastritis present delayed gastric emptying that is weakly related to the reduction of the acid secretion and the raising of serum gastrin levels rather than to the severity of the atrophy.     

Effect of Helicobacter pylori on Parietal Cell Sensitivity to Pentagastrin in Duodenal Ulcer Subjects

Chittajallu RS, Howie CA, McColl KEL. Effect of Helicobacter pylori on parietal cell sensitivity to pentagastrin in duodenal ulcer subjects. Scand J Gastroenterol 1992;27:857-862.

We have investigated the possibility that hypergastrinaemia in chronic Helicobacter pylori infection is a compensatory response to reduced parietal cell sensitivity to gastrin. The acid response to 45-min infusions of pentagastrin at sequential doses (mg/kg/h) of 0, 0.031, 0.062, 0.124, and 0.6 was compared before and 1 month after eradication of H. pylori in eight duodenal ulcer patients. The median acid outputs (mmol/h) with the respective infusions were 5.0, 7.5, 26.5, 30.8, and 37.0 when H. pylori-positive and similar at 4.5, 7.1, 22.7, 28, and 31.5 when H. pylori-negative. The median estimated dose of pentagastrin required to produce 50% maximal response (D₅₀) was similar before (0.060 mg/kg/h) and after (0.057 mg/kg/h) eradication of H. pylori. The median estimated maximal response to pentagastrin (mmol/h) was also similar before (39.2) and after (32.3) treatment. The median basal gastrin concentration was 48 ng/1 (range, 22-77) before treatment and fell to 33 ng/1 (range, 8-37) after eradication of H. pylori (p = 0.03). These findings show that the parietal cell sensitivity to pentagastrin is unaffected by chronic H. pylori infection in duodenal ulcer subjects and that the hypergastrinaemia cannot be attributed to the bacterium inhibiting parietal cell function.     

Gastric Emptying of a Liquid Meal in Health and Duodenal Ulcer Disease

In the present investigation an extension of the method of George was used, which allows the rate of emptying of the gastric content (GC) to be assessed. The aim of the study was to find out whether there is any difference in gastric emptying rate of a liquid meal of 750 ml 10% glucose (glucose monohydrate, mol. wt. 198) between healthy subjects and duodenal ulcer patients (DU). The straight numerical volume of GC, the logarithm and the square root of GC were related to time, and these functions were compared. The correlation coefficient for the regression line for these functions showed that data both for healthy subjects and DU gave a better fit to the GC/time and ?GC/time relationship than to a semi-logarithmic function, when the starting point at time zero was excluded. Regardless of the type of transformation of the basic data, there was no difference between healthy controls and DU as regards the regression coefficient, indicating that from 20 min after the installation of the test volume the GC is decreasing at the same rate in the two groups. When the straight numerical volume of GC was used, there was a significant difference in the extrapolated Y-intercept for the regression lines between healthy subjects and the DU, indicating an increased initial emptying in the DU patients. This was further confirmed when the volume emptied during consecutive 20-min periods was estimated. Furthermore, there was a shorter emptying time in patients with duodenal ulcer than in healthy controls.     

Circadian Acidity Pattern in Prepyloric Ulcers: A Comparison with Normal Subjects and Duodenal Ulcer Patients

Savarino V, Mela GS, Zentilin P, Malesci A, Vigneri S, Sossai P, Di Mario F, Cutela P, Mele MR, Celle G. Circadian acidity pattern in prepyloric ulcers: a comparison with normal subjects and duodenal ulcer patients. Scand J Gastroenterol 1993;28:772-776.

We used continuous 24-h pH monitoring to compare the circadian intragastric acidity of 36 patients with prepyloric ulcers (PPU) with that of 101 normal subjects (NS) and that of 206 patients with duodenal ulcer (DU). The ulcer crater was endoscopically ascertained in all cases, and PPU were located within an area up to 2 cm proximal to the pylorus. The pH curve pertaining to DU patients ran below that of NS during most of the circadian period, whereas the pH profile of PPU patients was higher than that of NS, and this was particularly true during the evening and the night. The acidity of PPU patients was significantly lower (p < 0.01) than that of NS during the night only, whereas it was lower (p < 0.05-0.001) than that of DU patients during each time interval analysed (24 h, nighttime, and daytime). Our findings show that the gastric acidity of PPU patients differs greatly from that of DU patients, since it is lower throughout the whole 24-h period, and particularly during the night. Thus these two entities are pathophysiologically different with regard to the acidity pattern and should be considered two distinct subgroups of peptic ulcer disease instead of being incorporated, as usually happens, in the clinical group ‘duodenal ulcer disease’.     

Comparison of the Effect of Histamine and Pentagastrin on Gastric Secretion in Ulcer Patients

The effect of subcutaneous histamine dihydrochloride (24 μg per kg body weight) and pentagastrin (6 μg per kg) on volume and gastric acid output was compared in 18 ulcer patients. The time course for the volume or acid response to histamine and pentagastrin was very similar. Neither volume output nor acid output, expressed as maximal output per 15 minutes or peak 30-minute output independent of time after the injection of the stimulants, differed significantly. A highly significant correlation was found between both the volumes and the acid outputs after histamine and pengagastrin.     

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.     

Gastric Acid and Pepsin Secretion after Single Oral Doses of Mifentidine in Healthy Subjects

Mifentidine represents a potential improvement in the class of H₂-receptor antagonists because of its long plasma half-life (10 h). The aim of this study was to evaluate the effects of mifentidine on pentagastrin-induced gastric pepsin and acid secretion in man. Nine healthy subjects participated in two separate sessions in which they were given randomly either a single oral dose of placebo or 10 or 20 mg of mifentidine, in accordance with an incomplete balanced block design. Basal secretion was measured 30 min before the administration of the drug, and 90 min later unstimulated gastric secretion was collected through a nasogastric tube for an additional 30 min. Then, 2 μg/kg/h pentagastrin were infused intravenously for 2 h, and gastric juice collected again in 15-min aliquots. Acid output was almost completely blocked by both doses of mifentidine during the unstimulated period (-99%). Pentagastrin infusion induced 10 times as much acid output as in the unstimulated phase. This dramatic increase was reduced by 32% with the low dose of mifentidine and to a major extent (-86%) with the high dose. The pepsin output was significantly inhibited by both doses of mifentidine during unstimulated (-83% and -82%) and stimulated (-49% and -71%) phases. Acid output correlated with the area under the mifentidine plasma levels (r=-0.69, p < 0.05). It is concluded that mifentidine is a potent inhibitor of both acid and pepsin secretion in man.