Maximal Acid Output Research Articles

Intravenous Pantoprazole as Initial Treatment in Patients With Gastroesophageal Reflux Disease and a History of Erosive Esophagitis: A Randomized Clinical Trial

We sought to evaluate safety and efficacy of IV pantoprazole when used as initial therapy in patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis (EE) in a double-blind, placebo-controlled, randomized, parallel-group study. Patients were randomized to 7 days of once-daily IV or oral pantoprazole (40 mg) or placebo. Efficacy variables included maximal acid output, basal acid output, and changes from baseline in frequency/severity of GERD symptoms, and frequency of antacid usage. Seventy-eight patients were randomized (n=26/27/25 [IV/oral/placebo]). Mean maximal acid output was 8.4, 6.3, and 20.9 mEq/h for IV or oral pantoprazole, and placebo, respectively. For pantoprazole versus placebo, maximal and basal acid output were significantly lower (P<.001) and there was a numerical trend toward improved GERD and antacid usage. Both treatments were well tolerated. In conclusion, IV/oral pantoprazole were similarly effective in suppressing basal and pentagastrin-stimulated gastric acid secretion in GERD patients with a history of EE.

Effect of naproxen on gastric acid secretion and gastric pH

The mechanisms for the non-steroidal anti-inflammatory drug-induced inflammation in the stomach are unclear. To determine if naproxen (Naprosyn, Roche, Nutley, NJ, USA) alters basal acid output, pentagastrin-stimulated maximal acid output, or fasting gastrin. Basal acid output and maximal acid output gastric aspirations were performed pre-naproxen and 7 days post-naproxen 500 mg b.d. in 24 healthy subjects. Volume, pH and acid mEq were determined. Fasting gastrin was obtained. Comparisons were made using paired t-tests (alpha = 0.05). Dosing with naproxen did not statistically decrease mean pH of the basal acid output gastric fluid (3.3 vs. 3.1; N.S.) or the pentagastrin-stimulated maximal acid output gastric fluid (2.7 vs. 2.6; N.S.). Basal acid output total volume was significantly decreased post-naproxen (84 vs. 61 mL/h; P = 0.01), with no change in maximal acid output total volume (196 vs. 188 mL/h; N.S.). Basal acid output mean gastric acidity was significantly increased post-naproxen (0.04 vs. 0.05 mEq/mL; P = 0.03), with no change in maximal acid output mean gastric acidity after naproxen (0.10 vs. 0.10; N.S.). Gastrin was not altered by dosing with naproxen. Naproxen does not influence total acid secreted but does decrease basal gastric fluid volume, thereby increasing basal gastric acid concentration. These observations define one mechanism by which non-steroidal anti-inflammatory drugs may induce gastric injury.

Gastric histology, serological markers and age as predictors of gastric acid secretion in patients infected with Helicobacter pylori

Background: Acid secretion is intimately associated with most upper gastrointestinal diseases. Helicobacter pylori infection is a major environmental factor modifying acid secretion. Aim: To study the association between the pattern...

Inhibition of Epidermal Growth Factor Receptor Activation Enhances In Vivo Histamine-Stimulated Gastric Acid Secretion in the Rat

Epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) have been shown to inhibit gastric acid secretion through stimulation of the EGF receptor (EGFR). In this study we examined in vivo the effects of inhibition of the EGFR on histamine-stimulated acid secretion in the rat. Submaximal (1.5 mg/kg/hr) histamine-stimulated acid secretion was measured (microEq H(+)/2 hr) during infusion of EGFRtk inhibitors and ranitidine in anesthetized rats. EGFR phosphorylation in gastric mucosal tissue lysates was measured by Western blot analysis. Submaximal histamine-stimulated acid secretion was increased significantly by the EGFR inhibitors tyrphostin (Tyr) A46 and Tyr AG1478. Tyr A46 prevented TGFalpha (10 microg/kg/hr)-mediated inhibition of maximal (5.0 microg/kg/hr) histamine-stimulated acid output. Histamine caused a fourfold increase in EGFR phosphorylation which was inhibited by both Tyr and ranitidine. We conclude that the EGFRtk inhibitors, Tyr A46 and Tyr AG1478, significantly increased submaximal histamine-stimulated acid output and Tyr A46 prevented TGFalpha inhibition of histamine-stimulated acid secretion. These observations suggest that the EGFR is involved, in vivo, in the regulation of gastric acid secretion.

Early results of surgery in patients considered cimetidine failures.

Fifty-two consecutive unselected duodenal ulcer patients (Group I), who had failed to respond to cimetidine and who subsequently underwent elective vagotomy and drainage, were studied. All patients were symptomatic on cimetidine in full recommended dosage. This group has been compared with another group of 634 duodenal ulcer patients (Group 2) undergoing elective vagotomy and drainage in the 'pre-cimetidine era'. The groups were similar pre-operatively with regard to age, sex, length of history and maximal acid output. Completeness of vagotomy and amount of acid reduction were similar in the two groups. The incidence of recurrent ulceration was 5 per cent in Group I and 5.7 per cent in Group 2. Although, of necessity, follow-up is shorter in the cimetidine failures (mean 2.3 years), there is nothing to suggest that failure to respond to cimetidine precludes a satisfactory surgical result.

Selection of operation for duodenal ulcer based on acid secretory studies--a reappraisal.

Abstract The incidence of recurrent duodenal or jejunal ulceration was assessed 5–10 years after selective surgery for duodenal ulceration in 253 patients after vagotomy and drainage and in 55 patients after vagotomy and antrectomy. In the vagotomy and drainage group 8.6 per cent of the patients developed proven or highly suspected recurrent duodenal or jejunal ulcer. None of these patients had preoperative maximal acid output (M.A.O.) values less than 25 mEq. per hour. No recurrent jejunal ulcers occurred in the vagotomy and antrectomy group despite the fact that they had the same incidence of incomplete vagotomy by Hollander's criteria as the vagotomy and drainage group. It is suggested that a policy of selection of patients for vagotomy and drainage based on a preoperative M.A.O. of 25 mEq. per hour seems more justified and realistic than the previously used level of 40–50 mEq. per hour. Vagotomy and antrectomy should probably be employed if the M.A.O. is greater than 25 mEq. per hour.

A laboratory appraisal of the effects of truncal and selective vagotomy.

Abstract Maximal acid output and insulin tests were carried out in a series of 56 consecutive patients who had either a truncal or a bilateral selective vagotomy and drainage operation. The results of the insulin tests are discussed in the light of criteria established by several authors. The postoperative reduction in basal and maximal acid output was considered, and also the risk of recurrent ulceration. A comparison of the test results of the two types of vagotomy was made, and no significant difference was found.

Lack of necessity for corrections for pyloric losses and duodenogastric reflux in the performance of gastric secretory studies.

Gastric secretory studies are subject to considerable error owing to incomplete collections and to contamination by reflux of alkaline duodenal contents. Corrections for these sources of error have been defined, and they have been extensively applied in a research setting. In order to assess their utility in the performance of routine gastric secretory studies, the value of such corrections was assessed in 56 studies in patients with duodenal ulceration (10), previous surgical vagotomy (8), reflux oesophagitis (30) and primary oesophageal motility disorders (8). The effect of such corrections was small, and there were close correlations between uncorrected and corrected acid outputs in all four groups. The status of the vagal efferent gastric fibres was assessed by comparing the acid output after insulin hypoglycaemia with the maximal acid output after pentagastrin (insulin: pentagastrin ratio). The application of the corrections did not alter the conclusion regarding the assessment of vagal status in 55 of the 56 studies performed. It is concluded that such corrections are not necessary in the routine performance of gastric secretory studies.

The place of pylorus-preserving gastrectomy in the treatment of duodenal ulcer.

Abstract Forty-seven patients with chronic duodenal ulceration have had a pylorus-preserving gastrectomy carried out. The mean reduction in maximal acid output after the procedure was 65 per cent. Pyloric sphincter function appeared normal postoperatively and gastric emptying time was slow without stasis. Postoperative dumping was absent and there has been no evidence of recurrence. In spite of retention of a cuff of antrum circulating gastrin levels are greatly reduced. The results appear to justify the use of the procedure for uncomplicated duodenal ulcer.

Pylorus-preserving gastrectomy in the treatment of duodenal ulcer.

Abstract Twenty patients with duodenal ulcer have been treated by a pylorus-preserving gastrectomy. A functioning pyloric sphincter was maintained by retaining a 2-cm. cuff of antrum and carrying out a Billroth-I type of resection proximally. Basal acid output was reduced by 52.4 per cent and maximal acid output by 65 per cent. Gastric emptying time was prolonged, without producing stasis. A provocative test for the presence of dumping produced symptoms in only 1 patient following this operation in comparison with a high incidence of symptoms in patients who had had a Polya gastrectomy or vagotomy and drainage. The results suggest that the procedure may be of value in the treatment of chronic duodenal ulcer.

Fasting and postprandial serum gastrin levels before and after highly selective gastric vagotomy, truncal vagotomy with pyloroplasty and truncal vagotomy with antrectomy: Is there a cholinergic antral gastrin inhibitory and releasing mechanism?

Fasting serum gastrin levels and postprandial gastrin response were measured before and 1 month after highly selective vagotomy, truncal vagotomy with pyloroplasty and truncal vagotomy with antrectomy. The three groups of patients, 12 in each group, were closely matched for age, sex, maximum acid output and completeness of vagotomy. After highly selective and truncal vagotomy an identical and significant increase in fasting gastrin was observed, whereas after truncal vagotomy with antrectomy the pre- and postoperative fasting gastrin levels were not different. The net postprandial gastrin output over basal value was significantly increased after highly selective vagotomy, unchanged after truncal vagotomy and significantly lowered after truncal vagotomy with antrectomy. These results suggest the presence in the intact subject of a cholinergic inhibitory mechanism in the gastric body and fundus for the release of antral gastrin in the fasting and postprandial states and a possible cholinergic facilitatory mechanism for the release of antral gastrin after meals.

Acid-fundic selective vagotomy of the stomach without drainage in the treatment of duodenal ulcer: technique and results.

Abstract Out of 415 patients with duodenal ulcer under-going vagotomy in the past 6 years, 198 truncal vagotomies (T.V.) and 217 selective vagotomies (S.V.) were performed. Of the 217 S. V. s, 134 cases had a total selective vagotomy of the stomach (preserving the pyloroduodenal nervous peduncle), and in 83 cases a proximal selective vagotomy was performed (preserving also the antral branches of the two principal nerves of the gastric lesser curve or Latarjet nerves). The authors prefer the name ‘acid-fundic selective vagotomy (A.F.S.V.) of the stomach’ for the latter procedure. In 89 of the patients having S.V. no gastric drainage procedure was performed; in 27 of these a total S.V. had been performed and in 62 cases an A.F.S.V. In patients undergoing S.V. without gastric drainage the clinical results and gastric emptying were fairly good in the cases with a total S.V. (follow-up time, 12 months), and very good in the cases with an A.F.S.V. (follow-up time, 6 months). Basal acid output (B.A.O.) and maximal (pentagastrin-stimulated) acid output (M.A.O.) were evaluated in those patients undergoing A.F.S.V. before and 10 days after operation. B.A.O. was reduced by 80.5 per cent and M.A.O. by 68.5 per cent. An insulin test performed 3 months after operation was negative in 80 per cent of cases (complete vagotomy); in the other cases the vagotomy was adequate. Clinical results, although after only a short follow-up, suggest that the procedure can be considered as the treatment of choice in most patients with an uncomplicated duodenal ulcer (76 per cent in our series). Gastric drainage is required only in cases of stenosing duodenal ulcer with delayed gastric emptying. Pyloroplasty is also mandatory in the treatment of bleeding ulcer and of perforated ulcer (if the suture is stenosing).

The Effect of Intragastric Ammonia Production on Titratable Gastric Acid Output in Helicobacter pylori-Infected Patients with Chronic Gastritis

The purpose of this study was to assess whether intragastric neutralization of HCl by ammonia in Helicobacter pylori-infected patients could meaningfully affect the titratable acid output as a measure of gastric acid secretion in a relation to the severity of infection. In 79 patients with different degrees of Helicobacter pylori infection and chronic gastritis, the basal acid output (BAO) and maximal acid output (MAO) after pentagastrin (6 microg/kg s.c.) was estimated. Cl- and NH4+ contents in these fractions were also assayed. H+/Cl- ratio in the MAO fraction was diminished in markedly infected patients (68.1 +/- 3.9%, vs 84.1 +/- 3.3% in noninfected patients; P < 0.005). Ammonium content was maximal in patients with marked infection (0.912 +/- 0.086 vs 0.149 +/- 0.034 mmol/hr in MAO [P < 0.001] and 0.475 +/- 0.063 vs 0.105 +/- 0.016 mmol/hr in BAO of noninfected patients [P < 0.001]), with intermediate values in mild and moderate infection. The NH4 +/(H+ + NH4+) ratio reached 27.01 +/- 7.34% in the BAO of moderately infected patients, vs 10.22 +/- 3.81% in noninfected patients (P = 0.05), and 7.25 +/- 1.06% in the MAO of markedly infected patients, vs 1.14 +/- 0.33% in noninfected patients (P < 0.001). The intragastric ammonia production affects the titratable acid output in Helicobacter pylori-infected patients dependent on the severity of infection. Therefore this factor should be taken into consideration in the evaluation of gastric secretory function in Helicobacter pylori-infected patients.

Serum pepsinogen concentrations as a measure of gastric acid secretion in Helicobacter pylori-negative and -positive Japanese subjects

Although previous studies have indicated that serum pepsinogen I levels, as well as the pepsinogen I/II ratio, were positively correlated with maximal gastric output, the relationship may be different between Helicobacter pylori-negative and -positive subjects. The aim of this study was to investigate the relation between serum pepsinogen concentrations and gastric acid secretion in H. pylori-positive and -negative subjects separately. The presence of H. pylori infection, the serum pepsinogen concentrations, and gastric acid secretion were investigated in 182 subjects without localized lesions in the upper gastrointestinal tract. Serum pepsinogen concentration was measured by radioimmunoassay, and maximal gastric acid output was estimated by an endoscopic gastrin test, as we have previously shown. In H. pylori-positive subjects, serum pepsinogen I levels and the pepsinogen I/II ratio were significantly correlated with gastric acid secretion, although the latter showed a better correlation (r=0.40 and 0.53, respectively). On the other hand, in H. pylori-negative subjects, serum pepsinogen concentrations were well correlated with acid secretion (r=0.57), but there was no relation between the pepsinogen I/II ratio and acid secretion. The correlations between serum pepsinogens and gastric acid secretion differ, depending on the presence or absence of H. pylori infection. With the use of serum pepsinogens as a simple measure of gastric acid secretion, therefore, consideration of H. pylori infection status is needed. Because the determination of the acid secretory level has some clinical implications in both H. pylori-positive and -negative subjects, its estimation by serum pepsinogen concentrations can be of practical use.

Comparison of the effects of intravenously and orally administered esomeprazole on acid output in patients with symptoms of gastro‐oesophageal reflux disease

Intravenous esomeprazole may be beneficial for patients who cannot take oral medications. To compare intravenous esomeprazole with oral esomeprazole for effects on maximal acid output during pentagastrin stimulation in patients with gastro-oesophageal reflux disease symptoms. In four separate open-label, randomized, two-way crossover studies, adult patients were administered esomeprazole 20 or 40 mg once daily either orally or intravenously (by 15-min infusion or 3-min injection) for 10 days and switched to the other formulation with no washout period. Basal acid output and maximal acid output were measured on days 11, 13 and 21. In the four studies (total of 183 patients), least-squares mean maximal acid output ranged from 3.0 to 4.1 mmol/h after intravenous esomeprazole 40 or 20 mg and from 2.2 to 3.3 mmol/h after oral esomeprazole 20 or 40 mg. Differences between formulations were small and not statistically significant but did not meet the prospectively defined criterion for non-inferiority of the intravenous formulation. Median basal acid output values ranged from 0.04 to 0.27 mmol/h after intravenous administration and from 0.05 to 0.25 mmol/h after oral esomeprazole. Intravenous esomeprazole is an acceptable alternative to the oral formulation for treatment of up to 10 days of duration.

Esomeprazole therapy for gastric acid hypersecretion in children with cystinosis

Oral cysteamine therapy prevents natural disease progression in children with cystinosis, but it may cause severe gastrointestinal (GI) symptoms through gastric acid-hypersecretion. The purpose of this study was to assess the value of esomeprazole in controlling cysteamine-induced acid-hypersecretion and GI symptoms in children with cystinosis. Subjects underwent upper GI endoscopy and biopsy, serum gastrin and cysteamine measurements as well as acid secretion studies (basal, maximal and peak acid output, BAO, MAO, PAO) before and during esomeprazole therapy. A symptom score (maximum 14 points) was devised to monitor symptoms. Twelve children (mean age 5.8 years) were studied. Cysteamine ingestion resulted in mean MAO and PAO significantly higher than mean BAO, both before and during esomeprazole therapy. PAO was usually within 60 min of cysteamine ingestion. Esomeprazole therapy significantly reduced MAO (P<0.01) and PAO (P<0.01). The mean symptom score fell from 6.4 to 0.7 (P<0.0001) during esomeprazole therapy. The mean final dose of esomeprazole was 1.7 mg/kg per day (range 0.7 mg/kg per day to 2.75 mg/kg per day). Plasma cysteamine levels were not affected by acid-suppression therapy. One child had multi-nucleated parietal cells. Cysteamine-induced gastric acid-hypersecretion and GI symptoms are dramatically reduced with esomeprazole therapy. Esomeprazole does not alter cysteamine absorption and is very well tolerated in children.

Low pH and Helicobacter pylori increase nuclear factor kappa B binding in gastric epithelial cells: A common pathway for epithelial cell injury?

Helicobacter pylori infection results in peptic ulceration and chronic gastritis through mechanisms which are not fully elucidated. Live H. pylori activate the pro-inflammatory transcription factor NF-kappaB in gastric epithelial cells. Patients may have peptic ulcer disease in the absence of H. pylori infection; therefore other factors contribute to the inflammatory process. Maximal acid output in patients with H. pylori infection and duodenal ulceration is significantly increased indicating a role for acid in the pathogenesis of mucosal ulceration. The effect of low pH on NF-kappaB activation in gastric epithelial cells has not been studied. Human gastric epithelial cells (AGS) were exposed to a range of pH changes in the presence or absence of H. pylori. NF-kappaB DNA-binding and cytosolic IkappaB-alpha were measured using electrophoretic mobility shift assay and Western blotting. NF-kappaB DNA-binding in gastric epithelial cells dramatically increased when the pH of the culture medium decreased. Increases in NF-kappaB nuclear binding were paralleled by decreasing amounts of cytosolic IkappaB-alpha. These findings were similar but less potent than those observed when cells were exposed to H. pylori. Low pH resulted in enhancement of H. pylori-induced NF-kappaB nuclear binding. DNA binding of NF-kappaB activation secondary to low pH was attenuated by PD98059 but not by SB203580. Similar to H. pylori, low pH potently and independently augments NF-kappaB nuclear binding in AGS cells and such activation appears to be mediated through MEK1-dependant signaling pathways.

No relationship between IL-1B gene polymorphism and gastric acid secretion in younger healthy volunteers

To investigate the influence of IL-1B-511 gene polymorphism on IL-1B mRNA expression and gastric acid output in individual with or without Helicobacter pylori (H pylori) infection. IL-1B mRNA expression and gastric acid secretion in 117 health volunteers were assayed using semi-quantitative RT-PCR and gastric juice assay, respectively. Pepsinogen (PG) I and II of 255 subjects (including 117 health volunteers) were also examined. T/T genotype individuals with H pylori infection had a more decreased PG I/II ratio. In gastric antrum mucosa, the individuals with H pylori infection had higher IL-1B expression than those without H pylori infection, but there was no obvious difference among each genotype. In gastric corpus, the individuals with H pylori infection had a significantly higher IL-1B expression than those without H pylori infection. IL-1B-511T/T genotype was markedly higher as compared with the other two genotypes. Both maximal acid output and basic acid output were similar among each genotype in IL-1B-511 gene locus, regardless of H pylori infection. IL-1B-511 T allele does not decrease gastric acid output, although it has a stimulated influence on IL-1B expression. Consequently, the pathway, through which IL-1B plays a central role in gastric cancer development, might not depend on low acid, but on the other regulation mechanisms.

Modulating the cytokine response to treat Helicobacter gastritis

The conventional view of gastric acid secretion is that a negative feedback mechanism arises in response to high acidity, such that somatostatin keeps G-cells and parietal cells from producing more gastrin and acid, respectively. When the stomach becomes infected, for example with Helicobacter pylori (H. pylori), the feedback mechanism is impaired. In animal models, our laboratory has demonstrated that other types of bacteria besides H. pylori can cause gastritis. For example, under conditions of low acidity, gastritis is secondary to bacterial overgrowth, not production of excessive acid, thus suggesting a new paradigm for the regulation of gastric acid secretion under inflammatory conditions. Cytokines, released during the gastric inflammatory response, including IFNγ, TNFα and IL-1β stimulate the G-cell to produce gastrin. Gastrin in turn triggers the release of acid, and hypergastrinemia suppresses somatostatin, the inhibitor of acid. The overall response results in maximal gastric acid output that acts as the stomach's most important anti-microbial agent. The increased acid secretion by the stomach in the presence of H. pylori seems to be part of the innate immune response, in that gastrin and somatostatin are reciprocally regulated by Th1 or Th2 cytokines, respectively. In a mouse model, we showed that octreotide, a somatostatin, analog, is an efficacious treatment for Helicobacter gastritis. In humans, octreotide might accelerate recovery from H. pylori infection, reducing the duration of antibiotic therapy.

Evaluation of the pharmacokinetics and pharmacodynamics of intravenous lansoprazole

To compare the pharmacokinetics and pharmacodynamics of lansoprazole 30 mg administered intravenously in 0.9% NaCl or in polyethylene glycol, or orally. Twenty-nine subjects received lansoprazole orally on days 1-7 and intravenous lansoprazole in NaCl on days 8-14. Blood samples were collected on days 1, 7, 8 and 14. Fasting basal acid output and pentagastrin-stimulated maximal acid output were determined on days -1, 8, 9 and 15. Thirty-six different subjects received one of four regimen sequences: intravenous lansoprazole in NaCl, intravenous in polyethylene glycol, per orally, or intravenous placebo, each for 5 days. Twenty-four hour intragastric pH was recorded on days 1 and 5. Intravenous and per oral lansoprazole for 7 days produced equivalent basal acid output and maximal acid output suppression. Pharmacokinetics and mean pH values with intravenous lansoprazole in NaCl or polyethylene glycol were equivalent. Both produced mean pH and percentages of time pH above 3, 4, 5 and 6 that were significantly greater than did per orally. Intravenous lansoprazole inhibits acid secretion as effectively in NaCl as in polyethylene glycol, and its onset of action is faster than per oral lansoprazole.