Comparison of maximal acid output and gastrin response to meals in Chinese and Scottish normal and duodenal ulcer subjects.

Maximal acid output (MAO) after pentagastrin stimulation and gastrin response to a standard meal was studied in 100 control and 200 duodenal ulcer subjects from each of two ethnic groups, Scots and Chinese. The acid output was significantly higher in the Scots than in the Chinese for both controls and duodenal ulcer patients. Despite correction for differences in body stature by expressing MAO as a function of the body weight, these differences persisted. In 45 pairs of closely matched patients with duodenal ulcer, the differences between the two ethnic groups remained significant, irrespective of whether MAO was expressed in absolute or weight corrected values. This indicates that differences in age, sex, family history, or duration of illness did not account for differences in acid output. In 20 pairs of normal control and 45 pairs of duodenal ulcer patients the fasting and post-prandial serum gastrin levels did not differ, significantly between the two ethnic groups. The proportion of acid normosecretors was significantly higher in the Chinese duodenal ulcer patients than in the Scottish. The reason for these differences in the gastric acid output between the two ethnic groups is not known and needs to be studied further.     

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.     

Effect of pentagastrin on histamine output from the stomach in patients with duodenal ulcer.

The role of histamine in acid secretion is controversial. Improvements in the techniques of histamine assay allow a better assessment of the relationship of histamine to acid secretion. Patients with duodenal ulcers were studied to determine the mucosal histamine responses to pentagastrin stimulation to relate the appearance of histamine in the gastric juice to acid production during stimulation, and to detect changes in the plasma histamine concentration during pentagastrin stimulation. There was a mean 27% fall (range 0-60%) in mucosal histamine concentration after pentagastrin. The output of histamine into gastric juice closely paralleled acid output in peak output acid duration. The histogram profiles of acid and histamine were similar in shape. In contrast with previous studies, plasma histamine concentration was found to rise during peak acid secretion (mean rise 65%). There was no relationship between initial mucosal histamine concentration and acid secretion or maximal gastric juice histamine. The association of histamine and gastric acid release found in these studies was so close that a functional relationship may be presumed. Our data are compatible with the hypothesis that pentagastrin acts on the parietal cell indirectly by causing histamine release in the gastric mucosa, which in turn releases acid from the parietal cells.     

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.     

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.     

Maximum acid output to graded doses of pentagastrin and its relation to parietal cell mass in Chinese patients with duodenal ulcer.

In groups of Chinese patients with duodenal ulcer and controls, increasing the dose of pentagastrin from the standard dose of 6 ug/kg or 12 ug/kg did not result in any change in the maximum acid output (MAO). Comparison of the MAO thus obtained with that reported in series of Occidental subjects suggested that the Chinese subjects had smaller MAO. Using the method of Card and Marks (1960), the parietal cells of resected stomachs were counted in a group of Chinese patients with duodenal ulcer. It was found that the parietal cell mass (PCM) correlated with the MAO, both PCM and MAO were significantly small in the Chinese series as compared with the Scottish series, but the acid output per unit parietal cell mass (MAO per 10(9) parietal cells) was not different in the two groups. These observations suggested that the Chinese patients with duodenal ulcer had smaller parietal cell mass compared with the Westerners.     

Effect of Helicobacter pylori on parietal cell sensitivity to pentagastrin in duodenal ulcer subjects.

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 (micrograms/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 micrograms/kg/h) and after (0.057 micrograms/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/l (range, 22-77) before treatment and fell to 33 ng/l (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.     

Characterization and evaluation of the pathogenic nature of duodenogastric reflux by measurement of intragastric choline and sialic acid in normal subjects and in patients with duodenal ulcer

The high choline content in pancreatic juice and bile-contaminated gastric juice samples suggested that intragastric choline content could be related to duodenogastric reflux (DGR). In 308 secretory tests in normal subjects (38) and in duodenal ulcer patients (DU) (270), acid, pepsin, sialic acid and choline outputs were measured in basal secretion and after pentagastrin, insulin or secretin modulation. The distribution of choline output values in basal secretion showed that 77% subjects had no or small choline amounts (less than 10 mumol/h) and another population had high output values (greater than or equal to 10 mumol/h). Choline hourly outputs greater than or equal to 10 mumol/h could be related with positive DGR. DGR did not seem to modify acid or pepsin secretion except if acid outputs were low: in these cases the neutralizing activity reduced acid outputs and resulted in a pepsin inactivation. DGR by itself increased sialic acid outputs as evidenced by mucus erosion. In normal subjects, weak mucus erosion might be due to proteolytic activity. In DU patients without DGR, erosion was increased but was due to the same mechanism. In DU patients with DGR, erosion was stronger and no relationship with proteolytic activity could be established because of the introduction of eroded duodenal glycoprotein into the stomach. Pentagastrin, insulin and secretin were able to induce DGR. Reflux could contribute to mucus erosion either by its detersive properties or by the proteolytic material coming from the pancreas.     

Effects of graded amounts of intragastric calcium on acid secretion,gastrin release,and gastric emptying in normal and duodenal ulcer subjects

We studied effects of graded concentrations of intragastric calcium on acid secretion, residual gastric volume, and serum gastrin and calcium levels. Intragastric titration was performed with solutions of isotonic mannitol or mannitol plus 2.5, 6, 16, 39, and 97 mM CaCl(2) in 10 normal and eight duodenal ulcer subjects. Acid secretion was significantly increased above control values by the two highest CaCl2 concentrations in normal subjects and by the three highest CaCl2 concentrations in ulcer subjects. Highest observed acid output to any concentration of CaCl2 was 55% of peak acid output to pentagastrin in normal subjects and 75% in ulcer subjects. Intragastric calcium also released gastrin; correlation between acid secretion and circulating gastrin was weak (r = 0.43, P less than 0.05). Serum calcium was slightly increased but did not correlate with acid secretion. Residual intragastric volume after both control and CaCl2 solutions was much less in ulcer than in normal subjects; calcium did not alter residual volumes.     

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.     

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.     

Plasma gastrin, daytime intragastric pH, and nocturnal acid output before and at 1 and 7 months after eradication of Helicobacter pylori in duodenal ulcer subjects.

Nine patients with Helicobacter pylori-related antral gastritis and history of duodenal ulceration were studied before and at 1 and 7 months after eradication of the infection by a 4-week course of tripotassium dicitrato bismuthate, metronidazole, and amoxycillin. The median basal gastrin concentration before eradication was 30 ng/l (range, 20-60) and fell to 20 ng/l (5-20) at 1 month (p less than 0.02) and 15 ng/l (5-20) at 7 months (p less than 0.01) after eradication. The integrated gastrin response to a peptide meal was 3650 ng/l.min (range, 1875-6025) before treatment compared with 1800 ng/l.min (range, 1200-3075) at 1 month (p less than 0.01) and 1312 ng/l.min (875-2625) at 7 months (p less than 0.03). Daytime intragastric pH (0900-2100 h) was similar before treatment (median, 1.4; range, 1.1-2.1) and at 1 month (1.4; 1.1-2.3) and 7 months (1.4; 1-2.2) after eradication. In five of the patients nighttime acid output (2300-0900 h) was also studied and was similar before (median, 86 mmol/10 h; range, 52-114) and at 1 month (76 mmol/10 h; 50-143) and 7 months (94 mmol/10 h; 63-106) after eradication. In conclusion, eradication of H. pylori is accompanied by a sustained fall in serum gastrin concentrations but is not accompanied by an early or late reduction of daytime intragastric acidity or nighttime acid output.     

Gastric acid response to graded dose of pentagastrin in duodenal ulcer]

To characterize gastric acid response and its age distribution in the patients with duodenal ulcer (DU), we conducted pentagastrin (PG) dose-response study and calculated maximal response (Vmax-c), half maximal dose of PG (Km-c), and the mean response to 0.22 microgram/kg/hr of PG as percent of highest observed response (SI). The mean values of basal secretion (BAO), Vmax-c, and SI in DU were significantly greater than those of normal subjects (N). The mean values of Km-c were significantly less than those of N. The greater BAO, Vmax-c, and SI, and less Km-c were observed in all age groups of DU. The results indicate that DU patients not only secrete more acid but also are more sensitive to stimulation by pentagastrin than N, and that the characteristics are common in all age groups of DU.     

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.     

Sufotidine 600 mg bd virtually eliminates 24 hour intragastric acidity in duodenal ulcer subjects.

In a double blind study, 24 hour intragastric acidity and 24 hour plasma gastrin concentrations were measured simultaneously in seven duodenal ulcer subjects on the fifth day of receiving either sufotidine 600 mg bd or placebo. Compared with placebo, during treatment with sufotidine 600 mg bd the median integrated 24 hour intragastric acidity was decreased by 95% (range 74% to 99%) from 1000 to 51 mmol/h/l, whilst the median integrated 24 hour plasma gastrin concentration increased from 416 to 927 pmol/h/l.