Basal Acid Output Research Articles

Patients with Multiple Endocrine Neoplasia Type 1 with Gastrinomas Have an Increased Risk of Severe Esophageal Disease Including Stricture and the Premalignant Condition, Barrett’s Esophagus

Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (MEN1/ZES). Although esophageal reflux symptoms are common in these patients, little is known about long-term occurrence of severe peptic esophageal disease including strictures and Barrett's esophagus (BE). The objective of the study was to prospectively analyze the frequency of severe peptic esophageal disease in ZES patients with and without MEN1. The study was conducted at a tertiary care research center. Two hundred ninety-five patients (80 = MEN1/ZES, 215 = sporadic ZES) participated in a prospective study. Assessment of MEN1, acid hypersecretion, upper gastrointestinal endoscopy/biopsies, and tumor status were measured initially and at each follow-up. Esophageal manometry was performed in 89 patients. Frequency and type of esophageal disease were correlated with clinical/laboratory/tumoral features of ZES/MEN1. In MEN1/ZES patients, esophageal stricture was 3-fold higher, BE 5-fold higher, and dysplasia 8-fold higher, and one patient died of esophageal adenocarcinoma. Esophageal symptoms were more frequent or severe in MEN1/ZES, but known risk factors for severe esophageal disease and ZES-specific features did not differ between MEN1/ZES and sporadic ZES. In MEN1/ZES, the onset of ZES was 10 yr earlier, and H2-antagonists were used longer and at lower doses. MEN1/ZES patients with esophageal disease differed from those without in that ZES diagnosis was delayed longer, esophageal symptoms were more frequent or severe, hiatal hernias were more frequent, esophagitis or pyloric scarring was more common, basal acid output was higher, and hyperparathyroidism was underdiagnosed. This study shows that MEN1/ZES patients have a higher incidence of severe esophageal disease including the premalignant condition BE and identifies factors important for their pathogenesis that need to be incorporated into their long-term treatment.

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.

Gastroprotection induced by capsaicin in healthy human subjects.

To evaluate the gastro-protective effect of capsaicin against the ethanol- and indomethacin (IND)-induced gastric mucosal damage in healthy human subjects. The effects of small doses (1-8 microg/mL, 100 mL) of capsaicin on the gastric acid secretion basal acid output (BAO) and its electrolyte concentration, gastric transmucosal potential difference (GTPD), ethanol- (5 mL 300 mL/L i.g.) and IND- (3x25 mg/d) induced gastric mucosal damage were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment. Intragastric application of capsaicin decreased the BAO and enhanced "non-parietal" component, GTPD in a dose-dependent manner. The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application, which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin, but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3x400 microg i.g. Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings.

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.

Zollinger–Ellison syndrome caused by solitary gastrinoma blocking the pancreatic duct: Enucleation and pancreatic duct repair

A 25-YEAR-OLD WOMAN presented in 1987 with persistent diarrhea (up to 30 bowel movements per day). She had a 5-year history of dyspepsia, 1 episode of hematemesis secondary to duodenitis, and a prior emergent cecectomy for a perforated cecal ulcer of questionable etiology. Fasting serum gastrin was 383 pg/mL (normal, <90 pg/mL), secretin-stimulated serum gastrin was 1200 pg/mL (normal rise, <200 pg/mL), basal acid output was 32 mEq/h (normal, 2-3 mEq/h), and peak acid output was 69 mEq/h (normal, 10-15 mEq/h), all establishing the diagnosis of Zollinger–Ellison syndrome. Computed tomography revealed a dilated pancreatic duct without evidence of a gastrinoma in the pancreas or liver. Directed ultrasound, however, identified a nodule in the head of the pancreas obstructing the pancreatic duct. Endoscopic retrograde pancreatography confirmed partial blockage of the main pancreatic duct (Fig 1). Further history and biochemical evaluation ruled out multiple endocrine neoplasia I. At operation, a solitary, 2.8-cm encapsulated gastrinoma was found in the head of the pancreas (Fig 2). During enucleation of the tumor, a tongue extended into the anterior wall of the pancreatic duct and required excision. The pancreatic duct was repaired over a silicone tube that was threaded into the duodenum. The tube functioned as a stent, maintaining a low pancreatic duct pressure by ren-

Idiopathic gastric acid hypersecretion presenting as a diarrheal disorder and mimicking both Zollinger???Ellison syndrome and Crohn??s disease

Many gastric acid hypersecretory states (basal acid output of greater than 15.0 mEq/h) exist for which the etiology is known, such as Zollinger-Ellison syndrome, systemic mastocytosis, antral exclusion, antral predominant Helicobacter pylori gastritis (antral G cell hyperplasia), chronic gastric outlet obstruction, short gut syndrome and basophilic leukemias. However, many hypersecretory patients have no identified etiology for their acid hypersecretion and are designated as idiopathic gastric acid hypersecretors with a basal acid output of greater than 10 mEq/h and a normal serum gastrin level. Because of the gastric acid hypersecretion these patients also commonly have an increased frequency of stools. Idiopathic gastric acid hypersecretion represents a known cause of gastric acid hypersecretion that is far more common than Zollinger-Ellison syndrome and it has a markedly different treatment regimen and natural history. We report a case of a patient with idiopathic gastric acid hypersecretion previously misdiagnosed as having Crohn's disease because of a presenting complaint of diarrhea and mimicking Zollinger-Ellison syndrome because her fasting serum gastrin level was elevated when incorrectly measured in the presence of antisecretory treatment.

Clinical outcome using lansoprazole in acid hypersecretors with and without Zollinger-Ellison syndrome: A 13-year prospective study

Unremitting gastric acid and pepsin hypersecretion causes serious persistent and relapsing lesions, but the natural history with medical treatment alone has not been well-defined. The aims of this study were to heal and prevent relapse of acid/peptic lesions during acid suppression and to analyze benefits and risks during long-term lansoprazole treatment. Sixty-seven patients (49 with Zollinger-Ellison syndrome [ZES], 18 without), with basal acid output (BAO) >15 mmol/h or >5 mmol/h if post-antrectomy (n = 9, all ZES), were treated with individually optimized doses of lansoprazole (7.5-450 mg/day; median, 75 mg/day) to reduce BAO to <5 mmol/h or <1 mmol/h post-antrectomy and underwent endoscopy every 3-6 months for up to 13 years (median, 6.25 years). Before treatment, 94% had duodenal ulcer, 64% had esophagitis, 60% had 1 or more bleeding episodes, 13% had perforated ulcers, 90% had pain, 60% had heartburn, and 40%-48% had diarrhea, vomiting, and/or weight loss. Forty-seven patients (70%) remained symptom- and lesion-free, whereas 13 (20%) had mild, transient relapses, and 7 (10%) had more complicated relapses. Overall, symptoms were reduced 90+%; ulcer or esophagitis relapsed in 4.8% of patients/year, unrelated to Helicobacter pylori , whereas complications declined to <2%/y. Post-antrectomy ZES patients had 3.6-fold higher relapse rates than unoperated ZES patients (67% vs 18%, respectively). With BAO >5 mmol/h in intact patients, relative risk of relapse was 4.1, confidence interval 2.1-8.1, P < .001. Twenty patients died, 3 as a result of ZES (2 metastatic gastrinomas). With individually optimized medical suppression of acid secretion, 90% of patients had good to excellent long-term outcomes without surgery, with an annualized total relapse rate of <5%.

Acute Effect of Gamma Irradiation on Gastric Acid Secretion and Gastric Mucosal Integrity in the Rat

The effect of 3- or 6-Gray (Gy) whole-body gamma irradiation on basal and stimulated gastric acid secretion was studied in pylorus-ligated rats. Different groups of rats were irradiated with a single 3- or 6-Gy fraction and examined 7 days after irradiation. Exposure to 3-Gy fraction led to marked increase in basal (nonstimulated) gastric acid output in the 4-h pylorus-ligated rat (47.5% compared with unirradiated controls). After exposure to 6 Gy, only 18.2% increase in gastric acid output was noted compared with unirradiated controls. Under pentagastrin or histamine stimulation, gastric acid secretion in those irradiated with 3- or 6-Gy fraction was markedly reduced compared to that of unirradiated controls. Exposure to 3- or 6-Gy gamma irradiation intensified the degree of gastric mucosal injury evoked by indomethacin or 50% ethanol in a dose-dependent manner. It is concluded that in the pylorus-ligated rat model, lower doses of gamma irradiation increase basal gastric acid secretion and impair the gastric mucosal barrier with marked increase in its permeability to H+ following stimulation of acid secretion or exposure to barrier breakers. Exposure to irradiation is likely to result in failure of the parietal cell to respond to direct stimulation with histamine or pentagastrin.

Rebound acid hypersecretion after long‐term inhibition of gastric acid secretion

Rebound acid hypersecretion develops after the use of acid inhibitors. To estimate the duration of hypersecretion and to elucidate the role of the enterochromaffin-like (ECL) cell in rebound acid hypersecretion. Patients waiting for anti-reflux surgery who had used a proton pump inhibitor daily > 1 year were included. All patients discontinued taking acid inhibiting drugs after the operation. Basal and pentagastrin stimulated acid output was measured at 4, 8, 16 and 26 weeks postoperatively. Oxyntic mucosal biopsies were collected before and 26 weeks after the operation for counting of histidine decarboxylase (HDC) immunoreactive cells. Serum chromogranin A (CgA) and gastrin were measured before and at 4, 8, 16 and 26 weeks after the operation. Pentagastrin stimulated acid secretion was higher at 4 and 8 weeks than at 26 weeks after the operation. Gastrin and CgA were significantly reduced at 4 and 8 weeks, respectively. The number of HDC immunoreactive cells was reduced by 60% at 26 weeks postoperative. Rebound acid hypersecretion lasts more than 8 weeks, but less than 26 weeks after long-term proton pump inhibition. The findings indicate that not only the parietal cell mass, but also ECL cell mass and activity are involved in the mechanism of acid hypersecretion.

Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment

Gastric carcinoid tumors occur in 15% to 50% of patients with multiple endocrine neoplasia-1/Zollinger-Ellison syndrome (MEN-1/ZES) but are thought to be benign. We report 5 patients with MEN-1/ZES with symptomatic, aggressive gastric carcinoid tumors that required surgical procedures. This was a retrospective chart review. Each patient had MEN-1/ZES. Each patient had innumerable gastric carcinoid tumors with symptoms. The fasting gastrin level was 47,000 pg/mL (normal, <200 pg/mL); the basal acid output was 79 mEq/hr (n = 3), and the age at surgical exploration was 47 +/- 6 years, with a duration of MEN-1 of 21 +/- 3 years and of ZES of 15 +/- 2 years. All patients had elevated 5-HIAA or serotonin levels. Somatostatin receptor scintigraphy showed increased stomach uptake in 4 patients (80%). Four patients had a total gastrectomy; 4 patients had lymph node metastases removed, and 3 patients had liver metastases resected. One patient who did not have a total gastrectomy had liver carcinoid metastases. These results demonstrate that gastric carcinoid tumors in patients with longstanding MEN-1/ZES may be symptomatic, aggressive, and metastasize to the liver. With increased long-term medical treatment and life expectancy, these tumors will become an important determinant of survival.

Gastric antisecretory effects of synthetic cannabinoids after central or peripheral administration in the rat

Previous studies have revealed that cannabinoid (CB)-receptor agonists inhibit gastric acid secretion stimulated by indirectly acting agents, but not by histamine. Aiming to investigate whether central or peripheral mechanisms are involved, the effects of the synthetic CB-receptor agonists WIN55,212-2 and HU-210, administered either intracerebroventricularly (i.c.v.) or intravenously (i.v.) to the anaesthetized rat with lumen-perfused stomach, against gastric acid secretion induced by pentagastrin were tested. Injected i.c.v., both WIN55,212-2 (50 and 100 μg/kg) and HU-210 (25, 50 and 100 μg/kg) were ineffective on either basal secretion or acid output induced by pentagastrin (7.7 μg/kg, i.v.). By contrast, i.v. injections of WIN55,212-2 (100 and 1000 μg/kg) or HU-210 (10–100 μg/kg) significantly inhibited pentagastrin-induced acid secretion, maximal reductions being 75.70 and 82.24% for WIN55,212-2 and HU-210, respectively. The gastric antisecretory effect of HU-210 was prevented by administration of the selective CB 1-receptor antagonist SR141716A (1000 μg/kg, i.v.). These results show that CB 1-receptors mediating inhibition of gastric acid secretion in the rat are mainly peripherally located.

INTRAVENOUS LANSOPRAZOLE IS EQUIVALENT TO ORAL CAPSULE IN SUPPRESSING PENTAGASTRIN-STIMULATED ACID OUTPUT

Purpose: Patients with erosive esophagitis (EE) may require short-term intravenous therapy due to their inability to receive medication orally. The purpose of this multicenter, open-label study was to compare the pharma-codynamics of 30 mg intravenous lansoprazole (IV LAN) to 30 mg oral lansoprazole (PO LAN) capsules in patients with EE. Methods:H. pylori–negative patients with >= Grade 2 EE confirmed by endoscopy received 30 mg PO LAN for 7 consecutive days followed by 30 mg IV LAN infused over 30 min for 7 consecutive days without a washout. In both periods, LAN was administered 1 hr prior to the morning meal. Pentagastrin-stimulated acid output (MAO) and basal acid output (BAO) were assessed 22 hrs and 21 hrs, respectively following the last dose of PO LAN (Day 8), first dose of IV LAN (Day 9) and last dose of IV LAN (Post-Treatment Day 1). The primary endpoint was MAO after the last dose of IV LAN as compared to that afterthe last dose of PO LAN. Secondary endpoints included BAO after the last dose of IV LAN as compared to that after the last dose of PO LAN. Therapeutic equivalence of the two formulations was established if the population average for IV LAN minus 120% of PO LAN was negative. To test the null hypothesis of IV-1.2 PO> = 0, one-sided Wilcoxon signed-rank tests were performed at a significance level of 0.05. Equivalence would be established by rejection of the null hypothesis. Safety was monitored by adverse events, vital signs, physical examinations, routine ophthalmic examinations, laboratory evaluations, electrocardiograms and IV infusion site assessments. Results: 68 subjects 19 to 72 yrs of age enrolled, including 51 males and 17 females; among them 57 received 7 doses of IV LAN as well as at least 7 doses of PO LAN. The median MAO (mEq/hr) was 7.72 on Day 8 and 7.25 on Post-Treatment Day 1. The median BAO (mEq/hr) was 0.73 on Day 8 and 0.45 on Post-Treatment Day 1. Equivalence of the two formulations was established for both MAO (p = 0.001, N = 56) and BAO (p = 0.011, N = 57). All adverse events were mild or moderate in severity. Both formulations were safe and well tolerated. Conclusions: This study confirms previous findings that IV lansoprazole is as effective at suppressing pentagastrin-stimulated acid output and as safe as the oral formulation in treating patients with EE. The IV formulation is an alternative for the short-term treatment in patients who are unable to take oral medication.

ESOMEPRAZOLE 40 MG ADMINISTERED INTRAVENOUSLY (I.V.) PROVIDES BETTER CONTROL OF BASAL AND STIMULATED GASTRIC ACID SECRETION THAN OMEPRAZOLE 40 MG ADMINISTERED I.V.

Purpose: This study compared the effect on basal and pentagastrin stimulated acid output (BAO and PAO) of single-dose i.v. administration of esomeprazole 40 mg and omeprazole 40 mg. Methods: This was an open, randomized, two-way cross-over study in 23 Helicobacter pylori-negative healthy male and female subjects (18 males; mean age: 26 years; mean body mass index: 22.8 kg/m). Both drugs were administered as single 30-minute i.v. infusions with a washout period of at least 6 days. BAO (1 h) and PAO (1.5 hrs) were determined at baseline, between 3–5.5 h and finally between 23–25.5 h after drug administration on each study day. Blood samples, taken during the first 12 hours, were used to determine the area under the plasma concentration-time curve (AUC) and maximum observed plasma concentration (Cmax) for both drugs. The PAO and BAO values were analyzed using a mixed model ANOVA. The mean for each treatment and the mean treatment difference were estimated with 95% confidence intervals (CI). As an interim analysis was performed when 12 subjects had been included in the study, a 97.5% CI was calculated for the mean difference in PAO measured 3-5.5 hours after dose. Results: At baseline the mean BAO and PAO were 4.4 mmol/h (95% CI: 3.0 to 5.8) and 34.0 mmol/h (95% CI: 30.2 to 37.2), respectively. Intravenous administration of esomeprazole 40 mg resulted in a more pronounced reduction in BAO and PAO both measured 3–5.5 h and 23–25.5 h after dose compared with omeprazole 40 mg i.v. (Table). The geometric mean AUC and Cmax values were 36% and 18% higher, respectively, for esomeprazole 40 mg i.v. compared with omeprazole 40 mg i.v. There were no serious adverse events and both drugs were well tolerated.Table: Basal and pentagastrin stimulated acid output (BAO, PAO).Conclusions: Esomeprazole 40 mg i.v. provides faster and more complete control of basal and stimulated gastric acid secretion throughout the 24-hour period than omeprazole 40 mg i.v.

Helicobacter pylori infection, iron absorption, and gastric acid secretion in Bangladeshi children

Nonheme-iron absorption requires an acidic milieu. Reduced gastric acid output as a consequence of Helicobacter pylori infection could be an important limiting factor for iron absorption. We measured gastric acid output and iron absorption from a non-water-soluble iron compound (ferrous fumarate) and a water-soluble iron compound (ferrous sulfate) in children with and without H. pylori infection. Gastric acid output was quantified before (basal acid output, or BAO) and after pentagastrin stimulation (stimulated acid output, or SAO) in 2-5-y-old children with iron deficiency anemia who were (n = 13) or were not (n = 12) infected with H. pylori. Iron absorption was measured by using a double-stable-isotope technique. H. pylori-infected children were studied before and after eradication therapy. BAO and SAO were significantly lower in the H. pylori-infected children (0.2 +/- 0.2 and 1.6 +/- 0.9 mmol/h, respectively) than in the uninfected children (0.9 +/- 0.7 and 3.1 +/- 0.9 mmol/h, respectively; P = 0.01 and P < 0.005). BAO and SAO improved to 0.8 +/- 1.3 and 3.3 +/- 2.4 mmol/h, respectively, after therapy. Iron absorption from ferrous sulfate was significantly greater than that from ferrous fumarate both before (geometric : 19.7% compared with 5.3%; P < 0.0001) and after (22.5% compared with 6.4%; P < 0.0001) treatment in H. pylori-infected children. Corresponding values for uninfected children were 15.6% and 5.4%, respectively (P < 0.001; n = 12). Iron absorption from ferrous fumarate was significantly lower than that from ferrous sulfate in both H. pylori-infected and uninfected Bangladeshi children. Treatment of H. pylori infection improved gastric acid output but did not significantly influence iron absorption. The efficacy of ferrous fumarate in iron fortification programs to prevent iron deficiency in young children should be evaluated.

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.

Risk factors for esophagitis in extreme acid hypersecretors with and without Zollinger-Ellison syndrome

Background & aims Whereas severe duodenal ulcer is the hallmark of acid hypersecretion in Zollinger-Ellison syndrome (ZE) and similar states, the esophagus also is at high risk. We quantified the incidence of esophagitis and various risk factors that might contribute to it. Methods Sixty-eight acid hypersecretors (basal acid output >15 mmol/h), 50 patients with ZE, and 18 patients without ZE with normal gastrin levels were studied by gastric analysis, serum gastrin levels, and endoscopy. In 44 of 68 patients, esophageal manometry was performed after the esophagus had healed. Results Erosive esophagitis, grade 2 or worse, was found in 65%; an additional 15% had heartburn only, for a total reflux disease incidence of 80%. ZE accounted for 95% of severe esophagitis. Patients with and without esophagitis had the same high overnight fasting gastric residual volume and acidity, as well as basal and peak acid and pepsin outputs. However, patients with esophagitis had a lower median lower esophageal sphincter pressure (LESP) of 15.5 vs. 23 mm Hg in those without symptoms; the critical discriminator threshold was 16 mm Hg. Multivariate analysis further identified frequent vomiting and obesity as positive predictors of esophagitis, whereas Helicobacter pylori was a strong negative predictor (odds ratio, 0.16), possibly related to an elevated LESP in patients infected with H. pylori. Conclusions Erosive esophagitis is very common in acid hypersecretors. Identified risk factors that could promote abnormal esophageal exposure to the high acid and pepsin levels in our population of hypersecretors were vomiting, LESP < 16 mm Hg, and obesity, whereas H. pylori appeared to protect the esophagus not by reduced acid, but through an elevated LESP.

Intravenous lansoprazole: in erosive oesophagitis.

An intravenous formulation of lansoprazole, a proton pump inhibitor, is approved for use in patients with erosive oesophagitis who are temporarily unable to take oral lansoprazole. In healthy volunteers, oral and intravenous lansoprazole 30 mg/day were equivalent in suppressing basal and pentagastrin-stimulated maximum gastric acid output. Moreover, the mean 24-hour intragastric pH did not differ significantly following oral or intravenous administration of lansoprazole and was significantly higher with both formulations than with intravenous polyethylene glycol vehicle. After treatment for 7 days in patients with erosive oesophagitis, intravenous lansoprazole (30 mg/day) recipients had significantly lower median stimulated and basal gastric acid output measurements than placebo recipients. Median pentagastrin-stimulated gastric acid output levels were equivalent after 7 days treatment with intravenous or oral lansoprazole. Intravenous lansoprazole is generally well tolerated. All adverse events experienced by patients with erosive oesophagitis who received intravenous lansoprazole were mild or moderate in severity.

The evaluation and treatment of gastrointestinal disease in children with cystinosis receiving cysteamine

Objectives Cysteamine prevents organ damage in children with cystinosis, but may cause gastrointestinal (GI) symptoms. In this study we evaluated the nature of GI disease, and the value of omeprazole in controlling GI symptoms in these children. Study design Upper GI disease was evaluated with endoscopy, gastrin levels, and acid secretion studies after oral administration of cysteamine, before and after 16 weeks of therapy with omeprazole. A symptom score was devised. Results Eleven children (mean age, 5.7 years) were studied. After cysteamine ingestion, before and after omeprazole therapy, the mean maximum acid output was significantly higher than the mean basal acid output. The maximum acid output was measured within 60 minutes of cysteamine ingestion and was reduced by omeprazole therapy ( P<.01). The mean peak gastrin level was 30 minutes postcysteamine and was higher than baseline ( P<.01). The initial mean symptom score (maximum score, 14) was 6.9 and fell to 0.7 ( P<.0001) after 16 weeks of omeprazole therapy. At endoscopy, two children had diffuse gastric nodularity, and nearly all had cystine crystal deposits. Conclusions GI symptoms in children with cystinosis receiving cysteamine are often acid-mediated and improve with omeprazole. Cystine crystals were detected in the GI tract and may signify inadequate treatment with cysteamine.

Histopathology of the gastric oxyntic mucosa in two different patient groups during long-term treatment with omeprazole.

Hypochlorhydria, hypergastrinaemia, inflammation and Helicobacter pylori infection, dose and duration of omeprazole treatment may separately, or in combination, influence the proliferation of enterochromaffin-like (ECL) cells and parietal cell changes in gastric mucosa. To assess the effects of these variables comparisons were carried out in patients with the acid related Zollinger-Ellison syndrome (ZES) versus patients with progressive systemic sclerosis (PSS) and gastro-oesophageal reflux disease. Twenty-five patients with PSS and 16 patients with ZES were included and received continuous omeprazole treatment for a mean of 7.5 and 9 years. The patients were investigated every 6-12 months with endoscopy, biopsies and histology, and plasma gastrin measurements. PSS patients were titrated by 24 h pH-metry to oesophageal pH>4, and all ZES patients were titrated to a basal acid output of zero H+. Changes towards diffuse and linear ECL cell hyperplasia were observed in 41% of the PSS patients. Micronodular hyperplasia and neoplasia were not seen. In the ZES patients changes towards linear and micronodular hyperplasia were observed in all patients. Two patients developed ECL cell carcinoids; one of these had MEN-1 syndrome. Also parietal cell changes were more pronounced in the ZES group than in the PSS group. In patients without intrinsic acid hypersecretion and hypergastrinaemia significant proliferation of ECL cells is not an issue irrespective of gastric mucosal inflammation, omeprazole dose, duration of treatment and acid inhibition. The level of gastrin secretion and high plasma gastrin appear to accelerate ECL cell proliferation and parietal cell changes possibly influenced by chronic gastritis and H. pylori infection.

Histopathology of the gastric oxyntic mucosa in two different patient groups during long-term treatment with omeprazole

Objectives Hypochlorhydria, hypergastrinaemia, inflammation and Helicobacter pylori infection, dose and duration of omeprazole treatment may separately, or in combination, influence the proliferation of enterochromaffin-like (ECL) cells and parietal cell changes in gastric mucosa. To assess the effects of these variables comparisons were carried out in patients with the acid related Zollinger-Ellison syndrome (ZES) versus patients with progressive systemic sclerosis (PSS) and gastrooesophageal reflux disease. Methods Twenty-five patients with PSS and 16 patients with ZES were included and received continuous omeprazole treatment for a mean of 7.5 and 9 years. The patients were investigated every 6-12 months with endoscopy, biopsies and histology, and plasma gastrin measurements. PSS patients were titrated by 24 h pH-metry to oesophageal pH > 4, and all ZES patients were titrated to a basal acid output of zero H+. Results Changes towards diffuse and linear ECL cell hyperplasia were observed in 41% of the PSS patients. Micronodular hyperplasia and neoplasia were not seen. In the ZES patients changes towards linear and micronodular hyperplasia were observed in all patients. Two patients developed ECL cell carcinoids; one of these had MEN-1 syndrome. Also parietal cell changes were more pronounced in the ZES group than in the PSS group. Conclusions In patients without intrinsic acid hypersecretion and hypergastrinaemia significant proliferation of ECL cells is not an issue irrespective of gastric mucosal inflammation, omeprazole dose, duration of treatment and acid inhibition. The level of gastrin secretion and high plasma gastrin appear to accelerate ECL cell proliferation and parietal cell changes possibly influenced by chronic gastritis and H. pylori infection.