24-hour study of intragastric acidity in duodenal ulcer patients and normal subjects using continuous intraluminal pH-metry

The circadian pattern of intragastric acidity was assessed in 19 healthy subjects and 37 patients with active, endoscopically proven duodenal ulcer using 24-hr continuous intraluminal pH-metry. The median pH 24-hr profiles showed that ulcer patients had lower postprandial pH elevations and a smaller decline in acidity during the early morning hours when compared with controls. The after-lunch and -dinner area under the curve and maximum pH values were significantly higher in controls compared to ulcer patients. In the nighttime, the median pH values in controls were significantly higher during 9 pm to 12 pm (P=0.02), 12 pm to 4 am P=0.01), and 4 am to 8 am (P=0.0008) compared to the ulcer patients. We conclude that the 24-hr acidity is higher in ulcer patients compared to healthy subjects and that the differences are particularly evident in the postprandial and nocturnal periods.This work was supported in part by grant 86.02120.03 from CNR.     

Acid and gastrin responses during intragastric titration in normal subjects and duodenal ulcer patients with G-cell hyperfunction.

Amino acid induced acid and gastrin responses during intragastric titration at pH 2.5 and 5.5 were compared in normal subjects and duodenal ulcer patients with G-cell hyperfunction. The latter were identified on the basis of raised basal or maximal acid outputs and increased gastrin responses to feeding. In normal subjects the mixed amino acid meal stimulated only modest increases in serum gastrin, and the highest observed increase was about 30% that after a standard meal. In contrast, in the G-cell hyperfunction group the highest gastrin concentrations were similar to those after a standard meal. In the G-cell hyperfunction group the increment in serum gastrin at pH 2.5 expressed as a proportion of that at pH 5.5 was 0.29 indicating that the capacity of acid to inhibit gastrin release was well established in these patients. Acid secretory rates were close to maximal at both pH 2.5 and 5.5 during intragastric titration in the ulcer patients, but in normal subjects acid output was about 50% maximal at 2.5 and close to maximal at 5.5. The results suggest that the enhanced gastrin response to feeding in G-cell hyperfunction patients is because of increased sensitivity to amino acid stimulation rather than to diminished acid-inhibitory mechanisms.     

The effect of intragastric pH-variations on the gastric acid response to insulin hypoglycaemia in healthy subjects and duodenal ulcer patients.

The gastric acid response to i.v. injection of 0.15 U of soluble insulin/kg b.w. was determined in healthy subjects and duodenal ulcer patients during intragastric perfusion with water, 0.1 M HC1, and alkaline buffer (pH 8.3). Perfusion with hydrochloric acid significantly reduced the peak gastric acid output following insulin in 6 healthy subjects (reduction 45%, p less than 0.05) but had no significant effect on the peak gastric acid response to insulin in 7 DU patients (reduction 16%, p greater than 0.05). The 2.5-hour gastric acid response to insulin was, however, significantly reduced in both groups (56% and 35%, respectively) by exogenous acidification of the stomach. The gastric acid response to insulin hypoglycaemia in 3 DU patients was the same with intragastric water and alkaline buffer perfusion. The reduction of the gastric acid response to insulin hypoglycaemia by intragastric acidification corresponded to a reduced volume secretion and could not be ascribed to increased back diffusion of hydrogen ions or duodenal inhibition. These findings suggest that the gastric acid response to insulin hypoglycaemia is inhibited by a low intragastric pH in man, and that DU patients are less sensitive to the inhibitory mechanism than healthy subjects.     

Propagation of the gastric peristalsis in normal subjects and duodenal ulcer patients

The velocities of gastric peristaltic waves were measured on fluorographic series made in normal subjects and patients with duodenal ulcer. After an overnight fast, the subjects drank 250 ml of barium suspension. Sequential radiograms were taken every 2 s during 30 s after two pyloric ejections. Peristaltic waves were located and their displacements measured with an Apple Graphic Tablet. Wave progression diagrams and velocity histograms were drawn for each subject. The velocities were calculated every 2 s. A "spread index" Ip was determined for each subject, characterizing the irregularity of propagation. Mean frequency and mean velocity were greater in duodenal ulcer patients (3.6 c/min; 3.7 mm/s) than in normal subjects (2.9 c/min; 2.4 mm/s; p less than 0.001). Nevertheless, no significant difference was found between proximal or midcorpus and antral velocities, in ulcer patients as well as in normal subjects, contrarily to classical data. However, the velocities were not uniform along the stomach. The contractions spread unevenly and displayed transient slopes. The irregularities of propagation were more pronounced in normal subjects, ranging from 0 to 14 mm/s with 28 p. 100 of velocities less than 1 mm/s, then in ulcer patients (0 to 13 mm/s with 12 p. 100 of low velocities). The spread index Ip was greater in normal (ranged from 0.54 to 2.62) than in ulcer patients (ranged from 0.16 to 0.48; p less than 0.001). This study showed that the propagation velocity of the peristaltic waves and its regularity were different in normal subjects and in duodenal ulcer patients.     

Inhibition of pentagastrin-stimulated gastric secretion by duodenal acidification or administration of fat in normal subjects and in patients with duodenal ulcer

The inhibitory effect of duodenal acidification and intraduodenal fat infusion on pentagastrin-stimulated gastric secretion in normal subjects and in patients with duodenal ulcer was studied. Intraduodenal infusion of acid resulted in inhibition of HCl secretion found to be significant only in ulcer patients. Pepsin output, although lower during the first 15 minutes of duodenal acidification, later increased. Intraduodenal infusion of olive oil resulted in significant inhibition of HCl and pepsin output in both groups of patients, which was maximal 45–60 minutes after the beginning of fat infusion. Gastric secretion was more readily inhibited in ulcer patients than in normal subjects; this difference was particularly evident in inhibition of pepsin secretion. In addition, decrease in concentration of HCl and pepsin was observed to be significant only in ulcer patients. Mechanisms by which duodenal acidification and fat inhibit gastric secretion are discussed. The results obtained suggest that secretin, which is probably responsible for inhibition after duodenal acidification, is not the inhibitor during inhibition by fat. The ulcer patients were found to have unimpaired mechanisms of inhibition by acid and fat.     

Secretin provocation in normal and duodenal ulcer subjects

The secretin provocation test for gastrinoma is based on the premise that secretin decreases or has no effect on serum gastrin in normal and duodenal ulcer subjects while inducing a paradoxical rise in gastrinoma. We reexamined the serum gastrin response to pharmacologic amounts of secretin in normal volunteers (N = 17) and unoperated duodenal ulcer patients (N = 10). GIH secretin caused significant early gastrin rises from baseline in both groups (P less than 0.05). The gastrin response curves after secretin were not significantly different between normal and ulcer subjects. Similar gastrin rises were seen when synthetic secretin was administered to normal subjects (N = 6). In normal volunteers, intravenous bolus saline (N = 10) or amino acid (L-cysteine, N = 8) caused no change in serum gastrin from baseline. The gastrin response curves to GIH secretin and saline were significantly different (P less than 0.05). Our findings suggest that the gastrin rise in gastrinoma patients after secretin is an exaggeration of the normal response and not paradoxical.     

Somatostatin in gastric juice in normal subjects and patients with duodenal ulcer

Somatostatin in gastric juice was determined in normal subjects and patients with duodenal ulcer. Gel exclusion chromatography of gastric juice revealed that the main immunoreactivity existed at the position of somatostatin-14. A large amount of somatostatin was present in gastric juice, and the quantity increased following tetragastrin stimulation. Furthermore, there was a good inverse correlation between somatostatin concentration and acidity of gastric juice; however, there was no difference between normal subjects and patients with duodenal ulcer in the amount of somatostatin released into gastric juice.     

Comparison of an intragastric method of estimating acid output with the pentagastrin test in normal and duodenal ulcer subjects.

Using Fordtran's technique but substituting the meat extract Oxo for the steak meal we investigated gastric acid secretion in eight control subjects and nine patients with chronic duodenal ulcer. Intragastric titration was performed using a double lumen tube measuring the pH in the stomach every three minutes and adjusting it to 5.5 throughout the test by infusing 0.3-M sodium bicarbonate. On a separate day a pentagastrin test was performed using a conventional gastric aspiration technique. In the eight control subjects the mean acid output after pentagastrin was 13.7 +/- 2.1 (SEM) mmol/h, whereas the mean hourly acid output measured by intragastric titration was 20.1 +/- 3.1. The greater response to Oxo than to pentagastrin in the controls (deltaAO = + 46%) was significant (P less than 0.01). This is in contrast with our duodenal ulcer patients whose mean hourly acid outputs were 22.7 +/- 4.4 and 23.0 +/- 4.4 mmol/h in response to pentagastrin and Oxo respectively (r = 0.95). The findings, while clearly at variance with those of Fordtran and Walsh (1973), are more in keeping with the concept of increased endogenous secretory drive in duodenal ulcer patients compared to normal subjects.     

Consequences of antral and duodenal acidification on acid secretion, gastrin response and gastric emptying in duodenal ulcer patients and normal subjects

The present study intended to investigate the effect of antroduodenal acidification on gastric acid secretion and emptying, gastrin and somatostatin release in response to food in healthy subjects as well as in duodenal ulcer patients. Ten duodenal ulcer patients and 9 normal controls were studied twice: the same 400 ml liquid protein meal (proteins: 10 g) was introduced into the stomach; then intragastric pH was either maintained at pH 4.5 or allowed to decrease in response to the meal. Acid secretion was calculated using the intragastric titration method (for which the intragastric pH is fixed at pH 4.5) and using the serial dilution indicator method (which allows antral acidification) respectively. Gastric emptying was estimated according to: a) iterative measurements of intragastric meal residual volume; b) volume passing through the pylorus. These two tests were performed in a random order and during each, plasma gastrin and somatostatin responses to the meal were determined. In healthy subjects, antral acidification following the meal was associated with a significantly lower acid secretion (17.3 +/- 0.9 mmol/h; m +/- SEM) than when the pH was maintained at pH 4.5 (20.2 +/- 1.3; p less than 0.05). Moreover, gastric emptying was slower when the pH was allowed to decrease (t 1/2: 26.2 +/- 1.4 min) than when the pH was constant (t 1/2: 20.5 +/- 2.2 min; p less than 0.05). By contrast, in the duodenal ulcer group, neither acid output nor gastric emptying were significantly different in the two situations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gastric acid secretion rate and buffer content of the stomach after a rice- and a wheat-based meal in normal subjects and patients with duodenal ulcer.

The study describes gastric acid secretory response to a rice-based and a wheat-based meal over a prolonged period of five hours and buffer content of the stomach in five normal and seven duodenal ulcer subjects from the rice-eating eastern Indian population. The results suggest that (1) the meal-mediated gastric acid secretory response in duodenal ulcer subjects is much higher than in the controls, even though the histamine stimulated response is similar, (2) the type of meal, whether rice and fish based or wheat and meat based, does not influence the acid secretory response, and (3) the duodenal ulcer subjects in this area, two hours after a meal, have a buffer capacity similar to the controls.     

Dose-kinetics of pancreatic alpha- and beta-cell responses to a protein meal in normal subjects

A protein meal is well known to induce a prompt secretion of insulin and glucagon. However, the data regarding the dose-response relationship between the protein meal and the insulin and glucagon responses are sparse. This study assessed the effects of ingestion of protein meals of varying amounts on plasma glucose [S], insulin [I], and glucagon [G] concentrations in eight normal subjects. Protein meals were administered after an overnight fast in a randomized sequence at intervals of 10 days in four different quantities: 250 mg/kg body weight (BW) (A), 500 mg/kg BW (B), 1 g/kg BW (C), and 2 g/kg BW (D). Mean S levels were not significantly altered following A, B, or C, although significant decreases in S responses were noted after C and D as reflected by absolute changes (delta) and/or the cumulative responses (CR) and the areas under the curve (sigma). Mean I increased promptly to peak concentration by 30 minutes, although in individual subjects the peak was achieved either at 30 or 60 minutes following all protein meals. The increase was progressively greater and the return was delayed with increasing quantities resulting in progressive elevations in delta I and percent increase from basal concentration (%), as well as CRI and sigma I. G increased following all protein meals as well. The mean peak G concentrations were achieved by 90 minutes, although in individual subjects the peak G was reached at 90 or 120 minutes, a significant delay in comparison to the peak I levels. G returned to base line only following ingestion of A during the study period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gastric emptying of liquids in normal subjects and patients with healed duodenal ulcer disease

We have characterized the dose-response of inhibition of gastric emptying by acid, glucose, and fat in duodenal ulcer (DU) patients and normals (N) matched by age and sex. Gastric emptying was measured by the George technique while intragastric pH was maintained constant by intragastric titration. Acid, glucose, and fat inhibited gastric emptying in a dose-dependent fashion in both groups. DU patients emptied all three types of meals faster than normals, but differences were only seen at the lower doses of glucose or with the less potent doses of acid and fat. With low concentrations of glucose and at all concentrations of acid, DU patients emptied the meals faster than normals only in the first 5 min; but with fat the differences persisted throughout the 30-min test. Differences in gastric emptying of liquid meals in DU patients vs normals are small, and they occur with nutrient as well as acid meals. The variable responses obtained with the different concentrations may explain the inconsistencies found by other workers.     

Single dose ranitidine: influence of the time of administration on gastric acidity in normal subjects and in patients with duodenal ulcer

Using ambulatory 24 hour pH monitoring, intragastric acidity was measured in 6 healthy volunteers and 8 patients with duodenal ulcer. According to a latin square design each patient was randomly assigned to receive placebo, 300 mg ranitidine at 19.00 h or 300 mg ranitidine at 22.00 h, on three separate occasions. Validation of the method was achieved by comparing the values indicated by the intragastric electrode and the pH of simultaneously aspirated gastric juice (y = 0.87x + 0.66, r = 0.93). Comparing the area under the curve of intragastric hydrogen ion activity, as well as the percent of time less than pH 5, we found a better inhibition of nocturnal acidity (20.00 h-08.00 h) with 19.00 h ranitidine than with ranitidine administered at 22.00 h (p less than 0.01). By contrast, there was no significant difference in diurnal acidity between both ranitidine regimens and placebo.