Serum gastrin response to food stimulation in male azotemic patients.

In 37 patients with hypertension and/or renal disease, blood from a peripheral and a renal vein was drawn during renal vein catheterization. The serum gastrin concentrations were determined and found by paired comparison to be statistically significantly (p less than 0.05) higher in the peripheral than in the renal vein. A test meal was given to 9 male controls and 7 male azotemic patients, and the serum gastrin concentration response determined. The mean fasting serum gastrin values were 173 +/- 22 pg/ml in the group of patients versus 42 +/- 5.5 pg/ml in the controls. The serum gastrin response was significantly higher and of longer duration in the azotemic patients than in the controls. The pentagastrin-stimulated gastric acid secretion was, however, equal in the two groups.     

Dietary linoleic acid, gastric acid, and prostaglandin secretion

Basal and pentagastrin-stimulated gastric acid secretion, fasting serum gastrin concentrations, and the gastric output of prostaglandin E and its major metabolite 13,14-dihydro 15-keto prostaglandin E2 were measured in 9 normal subjects before and after 14-20 days of dietary supplementation with linoleic acid. Mean maximal gastric acid output fell from 36.0 +/- 3.3 (SEM) to 30.1 +/- 2.9 mmol/h (p less than 0.05), although mean basal acid output was not significantly affected (8.3 +/- 2.1 and 7.2 +/- 1.7 mmol/h, respectively). Mean fasting serum gastrin concentrations increased from 19.2 +/- 3.1 to 30.9 +/- 3.8 ng/L (p less than 0.01) after linoleic acid, probably because of acid suppression. The mean output of prostaglandin E increased from 498 +/- 110 to 1254 +/- 465 ng/h (p less than 0.05); that of its metabolite increased from 165 +/- 18 to 1168 +/- 645 ng/h (p less than 0.01). These findings show that in normal subjects essential fatty acid weakly inhibits gastric acid secretion, but considerably increases gastric prostaglandin output.     

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.     

Rebound nocturnal hypersecretion after four weeks treatment with an H2 receptor antagonist.

Daytime intragastric pH, fasting and meal stimulated serum gastrin and nocturnal acid output were studied in eight male duodenal ulcer patients before, during and two days after completing nizatidine 300 mg nocte (20:00 h) for four weeks. Median nocturnal acid output (mmol/10 h) decreased during treatment to 11.6 (range 0.4-26.7) compared with pretreatment value of 39.4 (9.8-91.2); median acid inhibition 77% (p less than 0.01) which was strongest between 24:00 and 04:00 h. Two days after discontinuing treatment, nocturnal acid output increased to 74.1 (11-181). Compared with the pretreatment value this represents median rebound hypersecretion of 77% (p less than 0.05), caused by increased H+ concentration and volume of secretion. Overall median daytime intragastric pH (09:00-21:00 h) was unchanged on the final day of treatment and two days after completing therapy, compared with the pretreatment values. Fasting serum gastrin measured between 09:30 and 10:00 h and the integrated gastrin response to an OXO breakfast taken out at 10:00 h were also similar during and after treatment, compared with pretreatment values. The rebound nocturnal hypersecretion may be relevant to the high ulcer relapse rates after stopping H2 receptor antagonists.     

Effect of simulated intragastric haemorrhage on gastric acid secretion, gastric motility, and serum gastrin.

The majority of upper gastrointestinal bleeds stop spontaneously despite the low pH and proteolytic activity of gastric juice which inhibit coagulation and platelet aggregation. In order to investigate this paradox six healthy male volunteers received intragastric infusions of 160 ml autologous venous blood or 160 ml egg white acting as control in random order on separate days. Basal acid output was calculated before infusion, net acid secretion and gastric volume emptied were calculated after intragastric infusions. Serum gastrin concentrations were also measured before and after intragastric infusions and expressed as the integrated gastrin response. Basal acid output (mmol/h) was 4.7 (1.9) (mean (SEM)) before egg white infusion and 5.9 (2.6) before venous blood infusion. After egg white infusion net acid secretion (mmol/20 min) increased to 5.6 (3.1) compared with 2.3 (1.3) after venous blood infusion (p less than 0.05). The gastric volume emptied (ml/20 min) was less after venous blood infusion at 105 (28) compared with 321 (66) after egg white infusion (p less than 0.03). Integrated gastrin response was similar after venous blood and egg white infusion. When compared with an equivalent protein meal intragastric blood stimulates less acid secretion and delays gastric emptying. This effect may facilitate haemostasis after gastric bleeding.     

Interactions between antral peptides and prostaglandin biosynthesis in gastric acid regulation in man

The role of endogenous prostaglandins as modulators of antral hormone release and gastric acid secretion was studied in the intact human stomach. The subjects (n = 9) received indomethacin prior to gastric perfusion at pH greater than 7 or less than 2 and subsequent vagal stimulation. Indomethacin was also tested against parenteral somatostatin (n = 10) and pentagastrin (n = 8). The release of somatostatin into the circulation was biphasic after vagal stimulation, and the plasma levels were inversely proportional to those of plasma gastrin. Acidification of the gastric antrum from pH greater than 7 to less than 2 increased twofold the basal plasma levels of somatostatin (p less than 0.05) and suppressed basal and vagally stimulated gastrin release (p less than 0.05) and gastric acid secretion (p less than 0.05). Indomethacin prior to acidification had little effect in the basal state. Following stimulation the release of somatostatin increased, as indicated by a twofold elevation of somatostatinlike immunoreactivity in the gastric lumen (p less than 0.05), but there was less inhibition of plasma gastrin (p less than 0.05) and gastric acid secretion (p less than 0.05) as compared to acidification alone. During alkaline gastric perfusion, indomethacin increased circulating somatostatin (p less than 0.05) levels without affecting plasma gastrin or gastric acid. Indomethacin given against intravenously infused somatostatin (0.1 microgram.kg-1.h-1) partially reversed the inhibited gastrin response to vagal stimulation without affecting somatostatin-suppressed gastric acid secretion. The effects of indomethacin against pentagastrin were marginal. In conclusion: Gastric acidification in man stimulates plasma release of somatostatin in parallel to suppressing gastrin release and gastric acid secretion. Endogenous prostanoids participate to regulate antral hormone interactions and may have dual actions on antral somatostatin, as negative modulators of release and as mediators of somatostatin effects on the gastrin cell. It is suggested that an unrestricted release of antral somatostatin is reflected in the gastric lumen rather than in the circulation.     

Effect of terbutaline, a beta 2-adrenoreceptor agonist, on gastric acid secretion and serum gastrin concentrations in humans

Because beta-adrenoreceptor agonists inhibit gastrin-stimulated gastric acid secretion in animals, we postulated that the beta 2-adrenoreceptor agonist, terbutaline, would inhibit pentagastrin-stimulated acid secretion in humans. Moreover, we hypothesized that terbutaline might inhibit food-stimulated acid secretion, as gastrin is a major mediator of food-stimulated acid secretion. Subcutaneous terbutaline (0.25 mg) reduced acid secretion during intravenous infusion of a submaximal dose of pentagastrin by 30%-40% (p less than 0.005), even though terbutaline increased serum gastrin levels (p less than 0.05). Furthermore, subcutaneous (0.25 mg) or oral (5 mg) terbutaline, given before a homogenized steak meal was infused into the stomach, lowered mean food-stimulated acid secretion rates, despite enhanced postprandial serum gastrin concentrations. Terbutaline also increased serum gastrin concentrations in patients with Zollinger-Ellison syndrome and in vagotomized individuals. Thus, beta 2-adrenoreceptor agonists enhance gastrin release while at the same time inhibiting gastrin-stimulated acid secretion in humans.     

Effect of parietal cell vagotomy on acid secretory responsiveness to circulating gastrin in humans. Relationship to postprandial serum gastrin concentration

To study the relationship between gastric acid secretion and serum gastrin concentration after vagotomy, gastric acid output and serum gastrin concentration were measured simultaneously during intravenous infusion of graded doses of human gastrin heptadecapeptide (G-17) in duodenal ulcer patients with parietal cell vagotomy and in unoperated patients with duodenal ulcer disease (controls). The curve relating serum gastrin concentration to gastric acid output was shifted downward and to the right after vagotomy; the peak acid output to G-17 was reduced by 50% (p less than 0.001). The serum gastrin concentration that produced half of peak acid output (EC50%) averaged 185.5 pg/ml after vagotomy and 74.1 pg/ml in controls (p less than 0.01). Mean basal and postprandial serum gastrin concentrations were twofold to threefold higher in vagotomy patients than in controls (p less than 0.005). However, when peak postprandial serum gastrin concentrations were used to predict acid secretion from curves relating serum gastrin to acid output, predicted acid secretion was only 12.6 mmol/h in vagotomy patients compared to 24.4 mmol/h in controls. Parietal cell vagotomy decreases "functional" parietal cell mass, as reflected by a 50% decrease in peak acid output, and also reduces the responsiveness of "functional" parietal cells to gastrin to such an extent that acid secretion is reduced after vagotomy despite basal and postprandial hypergastrinemia.     

Multiple duodenal ulcer: natural history and pathophysiology.

It has not been established whether multiple duodenal ulcer is associated with a different natural history, pathophysiology, and therapeutic response than a single duodenal ulcer. A consecutive series of 96 patients with two or more duodenal ulcers at endoscopy, representing 9.6% of the total number of new patients with duodenal ulcer seen during the period 1980-1985, were compared with a random series of 200 patients with single duodenal ulcer seen in the middle years of this period. Multiple duodenal ulcer was associated with higher (p less than 0.02) male to female ratio, more (p less than 0.05) late onset patients (those with ulcer symptoms starting after age 30 years, more (p less than 0.05) chronic cigarette smokers, and more frequent (p less than 0.05) moderate to severe deformity of the duodenal bulb. More (p less than 0.05) patients with multiple duodenal ulcer had abnormally low D50 derived from pentagastrin dose response tests, indicating that they were more sensitive to gastrin stimulation. Furthermore, their mean fasting and meal stimulated serum gastrin concentrations were significantly higher than those of patients with single ulcer (p less than 0.005), or of controls (p less than 0.05). Compared with single duodenal ulcer, multiple ulcer had significantly lower placebo healing rate, and required a higher dose of misoprostol (1200 v 800 micrograms/day) to achieve a similar healing efficacy at four weeks. We conclude that multiple duodenal ulcer is associated with different clinical features, pathophysiology, and possibly therapeutic response from single duodenal ulcer, and appears to represent the more aggressive side of the ulcer spectrum.     

Upper gastrointestinal findings in chronic renal failure

Twenty-nine patients with chronic renal failure were examined both during the predialytic stage and after active treatment (dialysis, transplantation) for upper GI diseases. They underwent a gastric dose-response secretion test, gastroduodenoscopy, radiologic upper GI series, and fasting serum gastrin determination. Upper GI diseases increased in the active treatment stage. At the time of examination, patients with these diseases had a positive ulcer history, duodenitis, duodenogastric reflux, and blood group O more often in the predialytic stage. Their stimulation sensitivity to pentagastrin and their acid secretion capacity were greater, and they were less achlorhydric. Their fasting serum gastrin level was also lower. They had less endoscopically discovered gastritis, but microscopically, with regard to gastritis, they did not differ from those who did not develop upper GI complications. In conclusion, in chronic renal failure upper GI findings increase after the active treatment. Secretion tests and endoscopy performed before active treatment give an indication of those who will develop upper GI complications during active treatment.     

Upper Gastrointestinal Findings in Chronic Renal Failure

Twenty-nine patients with chronic renal failure were examined both during the predialytic stage and after active treatment (dialysis, transplantation) for upper GI diseases. They underwent a gastric dose-response secretion test, gastroduodenoscopy, radiologic upper GI series, and fasting serum gastrin determination. Upper GI diseases increased in the active treatment stage. At the time of examination, patients with these diseases had a positive ulcer history, duodenitis, duodenogastric reflux, and blood group O more often in the predialytic stage. Their stimulation sensitivity to pentagastrin and their acid secretion capacity were greater, and they were less achlorhydric. Their fasting serum gastrin level was also lower. They had less endoscopically discovered gastritis, but microscopically, with regard to gastritis, they did not differ from those who did not develop upper GI complications. In conclusion, in chronic renal failure upper GI findings increase after the active treatment. Secretion tests and endoscopy performed before active treatment give an indication of those who will develop upper GI complications during active treatment.     

Effects of eight weeks'' continuous treatment with oral ranitidine and cimetidine on gastric acid secretion, pepsin secretion, and fasting serum gastrin

Gastric acid secretion, pepsin secretion, and fasting serum gastrin levels were measured in 23 patients with duodenal ulcer disease, divided into three groups which received either cimetidine 800 mg daily, cimetidine 1600 mg daily, or ranitidine hydrochloride 300 mg daily for eight weeks. Pentagastrin tests were carried out at intervals both before and after treatment. Each dose of cimetidine reduced acid secretion to 42% of control one week after starting therapy. Ranitidine reduced acid secretion to 33% of the pretreatment value. Acid secretion remained suppressed to these levels throughout treatment with each drug. Acid secretion returned to pretreatment levels in all patients one week after treatment and remained normal until the end of the study. Both drugs reduced pepsin, which fell to 64% and 61% (p less than 0.01) after 800 mg and 1600 mg cimetidine respectively and to 65% (p less than 0.005) with ranitidine after one week's treatment. Pepsin secretion remained at this reduced level in both cimetidine groups till the end of treatment. Pepsin levels fell to 50% at two weeks of therapy with ranitidine but stabilised at this level till the end of therapy. Cimetidine withdrawal was followed by a return towards pretreatment levels of pepsin secretion; but secretion remained significantly depressed (p less than 0.05) to the end of the study period. In the ranitidine-treated patients pepsin output returned to normal after drug withdrawal. Fasting gastrin levels rose during treatment with both drugs but failed to reach significant levels. After withdrawal of treatment fasting serum gastrin levels returned to normal in all three groups of patients.     

Effect of urogastrone on gastric secretion and serum gastrin concentration in patients with duodenal ulceration

A one-hour infusion of 0.25 micrograms/kg urogastrone administered to seven patients with duodenal ulceration resulted in significant reduction of basal acid secretion (p less than 0.05) but was without significant effect on basal pepsin and intrinsic factor secretion or on serum gastrin concentration. In another group of five patients with duodenal ulceration a one-hour infusion of urogastrone was given on five successive days. On day 1 and 5 urogastrone was administered after establishing a plateau response to intravenous pentagastrin 1.2 micrograms/kg/h. A mean reduction of 65% in acid output during the urogastrtone infusion was seen on day 1 and this was maintained during the next hour. On day 5 the pentagastrin-stimulated acid output was less than on day 1 and a further significant decrease was noted after urogastrone. Pepsin and intrinsic factor output were also significantly inhibited. There was no change in fasting serum gastrin or urogastrone concentration.     

H2 antagonists in the treatment of reflux oesophagitis: can physiological studies predict the response?

Ambulatory oesophageal pH, oesophageal manometry and fasting serum gastrin concentrations were carried out on 28 patients with reflux oesophagitis, before and during treatment with ranitidine 300 mg bd. Fourteen patients healed endoscopically at six weeks (group A) and 14 had residual oesophagitis (group B). Group A were characterised by a lower serum gastrin concentration before treatment (4.52 pmol/l; 2.4-10: mean and range) than group B (11.1 pmol/l; 3.5-21: p less than 0.05) and showed a marked reduction in acid reflux on treatment to near normal values. Mean per cent time below pH4 fell from 14.9 to 4.2 in group A (p less than 0.05) but was not affected in group B (14.2-15.6, not significant). Abnormal oesophageal motility was found in 13 patients from each group. This did not inhibit the response to ranitidine, and was not improved by healing of oesophagitis.     

Bombesin and G-17 dose responses in duodenal ulcer and controls

Gastric acid and pepsin secretion and serum gastrin concentrations were measured in nine patients with uncomplicated duodenal ulcer (DU) and 10 normal controls in the fasting state and in response to graded doses of bombesin, a tetradecapeptide gastrin releaser, and, for reference, synthetic gastrin G-17. Serum gastrin with bombesin stimulation was significantly greater in duodenal ulcer (maximum 467 pg/ml) than in controls (153 pg/ml), while in seven of the DU group tested gastrin levels after a meal were not different from that seen in five of the normal controls. Gastric acid concentrations and outputs were greater in duodenal ulcer with both stimuli. Secretory responses were then related to serum gastrin levels; despite increasing gastrin levels with bombesin stimulation, peak outputs achieved with bombesin were only 50% of G-17 maximum in normals and up to 90% of maximum in duodenal ulcer. Up to the point of peak response to bombesin, acid and pepsin outputs were the same with exogenous and endogenous gastrin, ie, bombesin acted only via G-17. Furthermore, in direct comparison of duodenal ulcer and normals with G-17 infusion, acid and pepsin outputs related to serum gastrin were congruent up to 75% of duodenal ulcer maximum, at which point normals reached their maximum level. These data have shown that duodenal ulcer patients are not more sensitive to either exogenous or endogenous gastrin; we have also shown regulatory defects in duodenal ulcer patients not previously described: (1) an exaggerated release of gastrin with bombesin stimulation, and (2) a defective inhibition of acid and pepsin secretion with higher doses of bombesin.Presented at AGA, Washington, D.C., 1983.     

Behaviour of acid secretion, gastrin release, serum pepsinogen I, and gastric emptying of liquids over six months from eradication of helicobacter pylori in duodenal ulcer patients. A controlled study.

The behaviour of basal and stimulated acid secretion, gastrin release, serum pepsinogen I, and gastric emptying of liquids was studied in 19 consecutive patients with Helicobacter pylori positive duodenal ulcer, over a follow up period of six months. Eleven patients were studied before and at three and six months after eradication with lansoprazole plus amoxicillin and tinidazole (case group), whereas the remainder, with persistent H pylori infection, were studied before and after three and six months from ulcer healing, thus constituting the control group. In the case group, three months after eradication, fasting serum pepsinogen I fell from (mean (SEM)) 91.9 (6.9) (pretreatment) to 72.2 (5.1) ng/l and the integrated gastrin response to a meal reduced from 11,470 (1174) (pretreatment) to 8130 (608) pg/ml/h (p < 0.05). Fasting serum gastrin concentrations and maximal acid output reduced significantly only six months after eradication. In contrast, no significant change of any of these measurements was seen in the control group either at three or six months from healing compared with the pretreatment values. Gastric emptying of liquids did not change over the entire period of follow up in both study groups. In conclusion, eradication of H pylori in duodenal ulcer patients is accompanied by a rapid fall in serum pepsinogen I and plasma gastrin concentrations, whereas a slight but significant reduction of maximal acid secretion takes place later on. In contrast, gastric emptying of liquids does not seem to be influenced by H pylori status.     

Effect of chronic antacid ingestion on serum gastrin and gastric secretion

Basal gastrin and acid secretion, and histamine- and food-stimulated acid secretion were examined before and after 6 weeks of regular antacid consumption by 20 normal volunteers, in order to test the hypothesis that regular use of antacids produces gastrin cell hyperplasia, altered gastrin inhibition by acid, and gastric hypersecretion. We found no differences in fasting serum gastrin, basal or maximal histamine-stimulated acid, or acid output in response to a protein meal after consumption of commercial antacids with or without calcium carbonate. The results suggest that normal subjects do not acquire functional hyperactivity of the gastrin mechanism after a period of regular antacid use.     

Effect of Intragastric Amino Acids on Lower Esophageal Sphincter Pressure and Serum Gastrin in Man

The effects of the intragastically administered individual L-amino acids, phenylalanine, tryptophan, glycine, aspartic acid, and leucine on lower esophageal sphincter (LES) pressure and serum gastrin concentration were studied in normal subjects. On separate days and in random, double-blind fashion, 13 adult male subjects received isotonic 0.1 M concentration of amino acids and saline, at pH 5.5 in a volume of 600 ml by rapid intragastric instillation over 5 min. LES pressure and serum gastrin concentration were monitored basally and then at frequent intervals for 90 min. Only tryptophan had a significant effect on LES pressure when compared with saline, decreasing LES pressure from 20 to 60 min after administration (p less than 0.01). Only phenylalanine and tryptophan produced significant stimulation of serum gastrin levels with peak increases above basal occurring 30 min after administration (p less than 0.05). It is concluded that: aspartic acid, leucine and glycine produced no significant changes in LES pressure or serum gastrin level; tryptophan and phenylalanine significantly increased serum gastrin concentration; tryptophan significantly decreased LES pressure whereas phenylalanine had no effect; the mechanism of inhibition of LES pressure by tryptophan is not defined and may be mediated by neural or hormonal pathways possibly involving a duodenal receptor.     

Role of thought, sight, smell, and taste of food in the cephalic phase of gastric acid secretion in humans

The relative importance of thought, sight, smell, and taste of food in the cephalic phase of gastric acid secretion has not been studied systematically. We found that discussing appetizing food for 30 min (without sight, smell, or taste) increased acid secretion from 4 to 13 mmol/h in healthy human subjects (p less than 0.001) and also increased serum gastrin concentrations significantly (p less than 0.02). Discussing food resulted in an acid secretory response that averaged 66% +/- 10% of the response to modified sham feeding, which activates thought, sight, smell, and taste. Discussing topics other than food (e.g., current events, sports) did not increase acid secretion significantly. The sight of appetizing food (without smell or taste), the smell of appetizing food (without sight or taste), or the combination of sight and smell (without taste) also increased acid secretion and serum gastrin concentrations significantly. However, sight and smell were significantly less potent stimulants of acid secretion than sham feeding, with responses averaging only 23%-46% of the response to sham feeding. These studies indicate that thinking about food is a potent stimulant of gastric secretion in healthy humans. Moreover, the sight and smell of food increase gastric acid secretion and serum gastrin concentrations, probably by provoking thoughts related to food.     

Gastric ulcer

In 15 patients with uncomplicated benign gastric ulcers, basal and peak gastric acid outputs and fasting serum gastrin levels were studied before and after healing. The mean basal acid output [4.0±1.3 (sem) mEq H⁺/hr], the mean peak acid output (29.5±5.1 mEq H⁺/hr), and the mean fasting serum gastrin level (80.3±16.7 pg/ml) in these patients did not change significantly with healing. Failure of gastric secretory function to change with healing suggests that mucosal resistance factors are more important than gastric acid secretion in the pathogenesis of a gastric ulcer.