Low Levels of Gastrin 17 are Related with Endoscopic Findings of Esophagitis and Typical Symptoms of GERD.

BACKGROUND AND AIMS: In clinical practice, most patients with symptoms suggestive of gastroesophageal reflux disease (GERD) undergo esophago-gastro-duodenoscopy (EGD), despite its low sensitivity in detecting reflux stigmata. Gastrin 17 (G-17) has been proposed to be related with GERD, due to the negative feedback between acid secretion and this hormone. We assessed the clinical usefulness of fasting G-17 serum determination for a non-invasive diagnosis of GERD in patients with typical symptoms. METHODS: We consecutively enrolled patients complaining of typical GERD symptoms in two different settings: a single referral center and a primary care setting. Control groups consisted of dyspeptic patients. All subjects underwent assessment of serum levels of G-17 and EGD. RESULTS: At the academic hospital, 100 GERD patients (n=89 with erosive esophagitis and 11 with Barrett's esophagus) had statistically significant low levels of G-17 as compared with 184 dyspeptic patients (1.7±1.2 pg/L vs 8.9±5.7 pg/L p<0.0001). Similarly, in the primary care setting, 163 GERD patients had statistically significant low levels of G-17 as compared with 132 dyspeptic patients (0.5±0.2 pg/L vs. 4.0±2.6 pg/L, p<0.0001). Moreover, in the primary care setting, no statistically significant differences were found for G-17 levels between patients with erosive and non-erosive reflux pattern (0.4±0.2 vs 0.7±0.3; p=0.08). In primary care, the accuracy of G-17 less than 1 pg/L to diagnose non-invasively GERD was 94.3%. CONCLUSIONS: Low levels of G-17 were detected in patients with erosive esophagitis and Barrett's esophagus in a referral center and in patients with typical GERD symptoms in a sample of patients from a primary care setting.

Leptin Aggravates Reflux Esophagitis by Increasing Tissue Levels of Macrophage Migration Inhibitory Factor in Rats.

Leptin, produced primarily by the adipose tissue, acts as a pro-inflammatory modulator, thereby contributing to the development of obesity-related disease. Although high levels of leptin in the obese are closely related to gastroesophageal reflux disease, the mechanism by which leptin influences esophageal inflammation remains unknown. Macrophage migration inhibitory factor (MIF) is produced by immune cells, such as T lymphocytes and macrophages, and MIF is known to induce the production of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6). We therefore investigated the mechanism whereby leptin aggravates reflux esophagitis, by focusing on esophageal tissue levels of MIF and CD3+ T lymphocytes, both of which are crucial for the reflux-induced epithelial damage. Esophageal inflammation was surgically induced in male Wistar rats by ligating the forestomach and narrowing the duodenum to facilitate gastroesophageal reflux, followed by administration of leptin or vehicle with an osmotic pump system for 1 week. We demonstrated that the administration of leptin exacerbated the reflux esophagitis with the apparent infiltration of CD3+ T lymphocytes and caused the significant increase in the esophageal tissue levels of MIF. Moreover, the leptin caused increases in the esophageal tissue levels of TNF-α, IL-1ß and IL-6, downstream targets of MIF. Importantly, the increases in these pro-inflammatory cytokines were accompanied by increased protein levels of phospho-STAT3 and phospho-AKT, pivotal molecules of leptin signaling pathways. In conclusion, through enhancing the MIF-induced inflammatory signaling, leptin could contribute to the development of gastroesophageal reflux disease.

Efficacy of On-Demand Therapy Using 20-mg Vonoprazan for Mild Reflux Esophagitis.

BACKGROUND: The study aimed to evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for mild reflux esophagitis (RE). METHODS: On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 24 weeks using 30 patients with mild RE who were receiving maintenance therapy with proton pomp inhibitors (PPIs). The presence or absence of RE, degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin level before breakfast were examined before and after on-demand therapy. The number of tablets taken during the 24-week period was also noted. RESULTS: One of the 30 patients dropped out of on-demand therapy 1 week after its initiation. Remission was maintained in 25 (86.2%) of the 29 patients (all 10 [100%] Los Angeles classification grade A patients and 15 (78.9%) of the 19 grade B patients). However, 4 grade B patients exhibited grade B relapse. There were no differences in the degree of overall satisfaction, score of symptoms or the gastrin level between PPI and on-demand therapies. The number of vonoprazan tablets taken during the observation period was 33 tablets (median)/24 weeks. CONCLUSION: On-demand therapy using 20-mg vonoprazan tablets is an effective alternative maintenance therapy for mild RE.

Does the Novel Potassium-Competitive Acid Blocker Vonoprazan Cause More Hypergastrinemia than Conventional Proton Pump Inhibitors? A Multicenter Prospective Cross-Sectional Study.

BACKGROUND/AIM: The long-term administration of proton pump inhibitors (PPIs) is useful for preventing recurrent reflux esophagitis. On the other hand, several adverse reactions, such as an increase in the blood gastrin level, have been reported. The aim of the present study was to examine the increase in the blood gastrin level due to the long-term administration of conventional PPIs compared with vonoprazan. METHODS: A prospective cross-sectional study was conducted. We examined the blood gastrin levels of patients taking vonoprazan or conventional PPIs in whom the grade of atrophic gastritis had been endoscopically evaluated in the last year. RESULTS: The blood gastrin level was significantly higher in the vonoprazan group than that in the PPI group in patients with milder or no atrophic gastritis, irrespective of the administration periods. However, no significant difference was observed between the groups in patients with severe atrophic gastritis. CONCLUSION: Vonoprazan more markedly increased the blood gastrin level compared with conventional PPIs in patients with milder or no atrophic gastritis. This indicates that vonoprazan may have stronger acid-suppressing effects in such patients than conventional PPIs. Key Message: We should be aware of the potential development of hypergastrinemia during the long-term administration of vonoprazan, especially in patients with mild or no atrophic gastritis.

Supplementation of Los Angeles classification with esophageal mucosa index of hemoglobin can predict the treatment response of erosive reflux esophagitis.

BACKGROUND: We assessed whether the esophageal mucosa index of hemoglobin (IHb) could assist the Los Angeles (LA) classification in defining the severity of erosive reflux esophagitis (RE) and predicting the treatment response by esomeprazole. METHODS: Five hundred twenty-four subjects (424 RE and 100 controls) with normal body mass index and hemoglobin had undergone endoscopy to confirm the RE grade by LA classification and to check the series of IHb values at every centimeter of the esophageal mucosa while withdrawing the endoscope to above the esophageal-gastric junction (EGJ). The RE cases had received esomeprazole for 8 weeks (40 mg/day) to assess the cumulative proportions of sustained symptomatic response (SSR). RESULTS: The IHb value at the EGJ was higher in RE patients than in controls (P < 0.001). Selecting 70 as the cutoff IHb value at the EGJ, the efficacy to define RE achieved 95.8% (406/424) sensitivity and 94% (94/100) specificity. For the patients with same the LA grade, the length of IHb value >70 above the EGJ (L-IHb70) that is greater than 4 cm correlated with a poor cumulative rate of SSR (P < 0.01). CONCLUSION: The IHb value >70 at the EGJ is a reliable indicator of RE. The L-IHb70 can serve as a supplementary indicator to predict the response to esomeprazole index within the same LA grade.

Study of arteriosclerosis in patients with hiatal hernia and reflux esophagitis.

BACKGROUND AND AIM: It has been reported that the prevalence of hiatal hernia (HH) and reflux esophagitis (RE) increases with age, as does the degree of arteriosclerosis. However, it has not been investigated whether or not arteriosclerosis is correlated with the presence of HH and RE. Therefore, we prospectively investigated the degree of arteriosclerosis in patients with HH and RE compared with subjects without HH and RE. METHODS: We prospectively enrolled 1683 people who visited Shimane Environment and Health Public Corporation for annual medical check-ups. All subjects were investigated by upper gastrointestinal endoscopy for the possible presence of HH and RE. Factors used for assessing cardiovascular risk were sex, age, body mass index (BMI), smoking and drinking habits, serum total cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol (HDLC). Arteriosclerosis was investigated by measuring systolic blood pressure, heart-carotid pulse wave velocity (HCPWV), bilateral ankle brachial index (ABI) and heart-ankle PWV (HAPWV). RESULTS: The number of patients with HH and RE was 624 (37.1%) and 143 (8.5%), respectively. The HDLC level of the patients with HH was significantly lower, and the levels of BMI, TG and arteriosclerotic parameters were higher than those of the subjects without HH after adjusting for confounding factors (sex, age and smoking and drinking habits). Cardiovascular and arteriosclerosis parameters except for TG did not differ between the subjects with and without RE. CONCLUSION: Levels of arteriosclerosis parameters in patients with HH were higher than in those without HH. However, the association between arteriosclerosis and presence of RE was not clarified.

Levels of serologic markers of celiac disease in patients with reflux esophagitis.

AIM: To investigate the prevalence of celiac disease serologic markers (antigliadin IgA, IgG, and anti-endomysial IgA) in patients with reflux esophagitis and to detect the relationship between reflux esophagitis and celiac disease (CD). METHODS: This study was performed prospectively between January 2003 and January 2004. Sixty-eight adult reflux esophagitis patients and 40 people as control group for symptoms related with gastrointestinal system were enrolled in this study. The diagnostic work-up included an accurate medical history with gastrointestinal symptoms, routine laboratory measurements, the detection of antibodies against gliadin (IgA and IgG) and endomysium (IgA), and an upper endoscopy with postbulbar biopsy. RESULTS: IgA-AGA and IgG-AGA were positive at 8.8% and 10.3% in patients with reflux esophagitis. In control group, it was found that 10% people had positive IgA-AGA, and 7.5% people had positive IgG-AGA. There was no significant relationship between patients and control group regarding positive IgA-AGA and IgG-AGA. The patients and persons in control group had no positive IgA-EMA. On postbulbar biopsies, no finding was detected concerning celiac disease. There were no symptoms and signs for gluten enteropathy in patients and control group. CONCLUSION: This review supports that an association does not exist between celiac disease and reflux esophagitis. We think these diseases exist independently from each other.

Therapeutic effects of 10 mg/day rabeprazole administration on reflux esophagitis was not influenced by the CYP2C19 polymorphism.

BACKGROUND: The acid suppressive effects of omeprazole (OPZ) and lansoprazole (LPZ) are influenced by the CYP2C19 polymorphism. On the other hand, some investigators have reported that acid suppressive effect of rabeprazole (RPZ) was not significantly affected by CYP2C19. The present study was designed to investigate whether the CYP2C19 genotype is related to the healing of reflux esophagitis (RE) in treatment with RPZ 10 mg. METHODS: One hundred and three Japanese patients with RE were treated with daily oral administration of 10 mg RPZ. At 4 and 8 weeks after the start of treatment, healing of RE was evaluated endoscopically. The CYP2C19 genotype was investigated before the treatment. RESULTS: At 4 weeks after the start of treatment, the healing rates for homo-extensive metabolizer, hetero-extensive metabolizer, and poor metabolizer patients were 83.3% (15/18), 77.3% (17/22), and 88.9% (8/9) [corrected] respectively, and at 8 weeks after the start of treatment, the healing rates were 86.1% (31/36), 92.0% (46/50), and 82.4% (14/17), respectively. There were no significant differences in the healing rate of RE among the three genotypes at either 4 or 8 weeks after the start of treatment. CONCLUSIONS: The therapeutic effects of 10 mg/day RPZ administration on RE may be uninfluenced by the CYP2C19 polymorphism.

Association between interleukin-1beta-511C/T polymorphism and reflux esophagitis in Japan.

BACKGROUND: Interleukin-1beta (IL-1beta) gene polymorphisms are related to hypochlorhydria and increase the risk of gastric cancer in the presence of Helicobacter pylori infection. However, little information is available about the genetic risk factors of reflux esophagitis. In this study we investigated its association with the IL-1beta polymorphisms. METHODS: We examined 48 patients with reflux esophagitis and 96 control subjects, 89 with gastric cancer. IL-1beta-511C/T genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The frequency of IL-1beta-511T alleles was significantly higher in reflux esophagitis patients (57.3%) than in controls (41.1%) (P = 0.0215, chi(2) = 5.289). The frequency of IL-1beta-511T/T genotypes was also significantly higher in reflux esophagitis patients (31.3%) than in controls (15.6%). The odds ratio and the 95% confidence interval were 4.000 and 1.393-11.486, respectively. The frequency of IL-1beta-511T/T genotypes was significantly higher in reflux esophagitis patients (31.3%) than in gastric cancer patients (21.4%). The odds ratio and the 95% confidence interval were 2.961 and 1.054-8.316, respectively. CONCLUSIONS: IL-1beta-511T was associated with reflux esophagitis having hyperacidity. Differences of genetic background regarding gastric acid secretion may exist between Japanese and Caucasians.

The effect of eight weeks of rabeprazole therapy on nitric oxide plasma level and esophageal pH and motility and motility nitric oxide plasma level in patients with erosive esophagitis.

BACKGROUND: Esophageal clearance, an important pathogenetic factor in gastroesophageal reflux disease, depends mainly on motility. Motility disturbances can be secondary to gastric output reflux. Nitric oxide influences esophageal motility. The aim of this study was to determine the effect of eight weeks of gastric acid secretion suppression with rabeprazole (20 mg/day) on esophageal motility. MATERIAL/METHODS: 20 patients with erosive esophagitis were studied. At study start and two weeks after the end of therapy, we recorded the results of interview, endoscopy, gastric and esophageal mucosa biopsy, 24-h esophageal pH-metry and manometry, and NO metabolites plasma concentration, determined spectrophotometrically (OXIS). RESULTS: All patients reported improvement and remained free of symptoms two weeks later. In 60% of cases, improvement of esophageal mucosa appearance was observed in endoscopic and histological examination. In follow-up we found a significantly smaller number of acid gastrooesophageal refluxes (p<0.05), reduced DeMeester score for pH range >7 (p<0.05), and greater % of time within the esophageal pH range 6-7 (p<0.05). Other esophageal pH-metry and 24-h manometry parameters did not change significantly. NO metabolites plasma concentration increased significantly (p=0.039). CONCLUSIONS: Clinical improvement after eight weeks of therapy with rabeprazole was connected with endoscopic changes only in 60% of our patients. Rabeprazole therapy did not influence esophageal motility, despite increased plasma levels of NO metabolites. Patients with erosive esophagitis need maintenance therapy, since as soon as two weeks after the end of treatment the % of monitoring time with esophageal pH<4 was similar to study start.

Effect of long-term, continuous versus alternate-day omeprazole therapy on serum gastrin in patients treated for reflux esophagitis.

BACKGROUND: Proton pump inhibitors have been proven to have a major role in the management of peptic diseases, especially the long-term control of reflux esophagitis. The potent inhibitory effect of omeprazole on gastric acid secretion is frequently associated with hypergastrinemia, and gastrin and its intermediates have been reported to promote gastrointestinal cellular functions and cell growth. Experimental data suggest that gastrin may affect the proliferation of colon cells and some other cancer cells. However, so far the direct role of gastrin in tumorigenesis is unclear. Although most clinical studies on long-term treatment with omeprazole or other proton pump inhibitors do not report serious adverse effects, the issue of prolonged hypergastrinemia and tissue growth is unsettled, and many clinicians are reluctant to recommend long-term use of omeprazole or of other proton pump inhibitors. STUDY: We examined the effect of long-term omeprazole treatment on serum gastrin levels in patients with reflux esophagitis when given either 20 mg daily (group 1) or on alternate days (group 2). During the follow-up period, clinical remission was monitored and maintained in all patients in group 1 and in the majority of patients in group 2. RESULTS: The mean serum gastrin level was significantly elevated in group 1 (mean +/- SE, 159 +/- 23.6 pg/mL; range, 45-620 pg/mL; n = 31) as compared with the alternate-day treatment group (group 2) (66 +/- 4.8 pg/mL; range, 37-115 pg/mL; n = 21) (p < 0.005). In controls, serum gastrin levels showed similar values to those found in group 2 (54 +/- 4.3 pg/mL; range, 27-94 pg/mL; n = 20). Fourteen patients (45%) in group 1 had serum gastric ranging from 140 to 620 pg/mL, and 8 (25%) had a 6-fold or greater increase in serum gastrin. The follow-up treatment period ranged between 3 and 60 months (mean +/- SE, 16.1 +/- 2.1 months) for group 1 and 3-36 months (9.7 +/- 1.4 months) for group 2. Upon multivariate adjustment for age and duration of treatment, a significantly lower mean serum gastrin level was observed in the alternate-day group as compared with the daily treated group. CONCLUSION: Alternate-day, long-term treatment with omeprazole may be adequate to maintain remission in patients with reflux esophagitis. This regimen can assure serum gastrin levels within the normal range, thus reducing the potential risk of prolonged, sustained hypergastrinemia and profound hypochlorhydria.

Increased release of interleukin-6 by oesophageal mucosa in children with reflux oesophagitis.

OBJECTIVE: To evaluate the release of interleukin-6 (IL-6) by oesophageal mucosa and to establish the serum levels of IL-6 and C-reactive protein (CRP), and plasma fibrinogen in children with reflux oesophagitis. DESIGN: In a prospective study, IL-6 release by tissue fragments obtained from oesophageal biopsies was determined and serum IL-6 and CRP as well as plasma fibrinogen were analysed. METHODS: The study population comprised ten children with reflux oesophagitis, diagnosed on the basis of 24 h oesophageal pH monitoring and endoscopy with biopsies. Ten children with recurrent abdominal pain were studied for comparative purposes. Biopsy tissue fragments were processed to obtain a cell suspension and the release of IL-6 was determined in culture medium. Serum IL-6 levels were measured by ELISA, serum CRP by turbidimetry, and plasma fibrinogen by spectrophotometry. RESULTS: Oesophageal cells obtained from reflux oesophagitis patients synthesize and release in vitro a significantly higher amount of IL-6 than controls (71.26+/-19.5 versus 31.67+/-8.02 pg/10(6) cells; P<0.01). Serum IL-6, serum CRP and plasma fibrinogen levels were not statistically different between patients with reflux oesophagitis and controls. CONCLUSIONS: These results suggest a short-term action of IL-6 since its effects could be exerted only in the microenvironment of the oesophageal mucosa.

Factors influencing corpus argyrophil cell density and hyperplasia in reflux esophagitis patients treated with antisecretory drugs and controls.

A cross sectional study was designed to elucidate the factors influencing the argyrophil cell population in patients with gastroesophageal reflux disease treated with omeprazole (N = 201) or H2-receptor antagonists (N = 118) and in control patients (N = 215). Fasting gastrinemia and Helicobacter pylori serology were determined. Gastritis, Helicobacter pylori infection, and argyrophil cell density and hyperplasia were evaluated in gastric biopsies. The argyrophil cell density was higher in both treatment groups than in controls (P = 0.002 and P = 0.051), whereas argyrophil cell hyperplasia was similar in the three groups. According to multivariate analysis, positive Helicobacter pylori serology was an independent parameter that decreased both density and grade of hyperplasia of argyrophil cells. Female gender and hypergastrinemia were independent factors increasing argyrophil cell density and hyperplasia, whereas antisecretory therapy, age and active gastritis were not. In addition, atrophic gastritis independently increased argyrophil cell hyperplasia. The prevalence of atrophic gastritis was significantly higher in Helicobacter pylori-positive than in negative patients and lower in the patients treated long-term with omeprazole than in the other groups.

Reflux esophagitis and airway hyperresponsiveness.

OBJECTIVES: To observe the effects of reflux esophagitis(RE) on the lung function and airway reactivity, and study the mechanism of airway hyperresponsiveness(AHR) in patients with RE. METHODS: Lung function measurements and airway provocation tests were performed in 31 RE patients and 35 control subjects. TXB2 and PGF1a were determined in 20 cases of each group. RESULTS: In RE patients the lung function was lower and the rate of AHR was higher than control subjects (P < 0.05). Among RE patients 25% had higher airway sensitivity (Dmin < 3 u). The TXB2 of RE patients with AHR was higher than those without AHR. Dmin correlated significantly with TXB2 (r = -0.653, P < 0.05). CONCLUSIONS: RE could damage the lung function. The rate of AHR was 61%, the high airway sensitivity was probably potential asthma, and TXB2 may play a role in the pathogenesis of AHR.

Helicobacter pylori gastritis and epithelial cell proliferation in patients with reflux oesophagitis after treatment with lansoprazole.

BACKGROUND: Helicobacter pylori gastritis may spread proximally in the stomach during profound acid inhibition. AIMS: To examine histological gastric body changes and epithelial cell proliferation before and after treatment with lansoprazole. PATIENTS AND METHODS: Patients diagnosed as having reflux oesophagitis grade 1 or 2 were enrolled and treated for 12 weeks with lansoprazole (30 mg every morning). After 12 weeks, 103 of the 118 patients appeared endoscopically healed and were asymptomatic; they then received maintenance treatment with 15 or 30 mg lansoprazole daily. Biopsy specimens obtained from similar sites before and after treatment, were available from 90 patients after a median of 64 weeks (range 15-73 weeks). Epithelial cell proliferation was determined by the number of Ki-67 antigen positive cells per gland. RESULTS: Of these 90 patients, 44 (49%) were found to be infected with H pylori. Their median inflammation score had increased from grade 1 before to grade 2 after treatment (p < 0.0001). Initially, the number of Ki-67 antigen positive cells per gland was significantly higher in the H pylori infected than in the uninfected group and increased further after treatment (p < 0.0001). In uninfected patients, no significant change in inflammation or proliferation occurred during treatment. CONCLUSIONS: A marked increase in body gastritis was observed in H pylori infected individuals during long term treatment with the proton pump inhibitor lansoprazole. Epithelial cell proliferation and atrophy also increased in infected but not in uninfected patients.

Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety.

OBJECTIVE: To evaluate the long-term efficacy and safety of omeprazole in patients with gastroesophageal reflux disease resistant to treatment with histamine-2 (H2)-receptor antagonists. DESIGN: Cohort analytic study with a mean follow-up of 48 months (range, 36 to 64 months). SETTING: Patients receiving ambulatory care from referral centers. PATIENTS: 91 patients with gastroesophageal reflux disease resistant to treatment with an H2-receptor antagonist but subsequently responsive to 40 mg of omeprazole daily. INTERVENTION: Open maintenance therapy consisting of 20 mg of omeprazole daily in 86 patients and 40 mg daily in 5 patients. OUTCOME MEASURES: Endoscopy to assess healing; side effects, laboratory values, fasting serum gastrin level, and gastric corpus biopsies to assess safety. RESULTS: Esophagitis recurred in 47% of the patients receiving 20 mg of omeprazole daily, but all rehealed after the dose was doubled. Seven of 40 patients (18%) had a second relapse after a mean follow-up time of 24 months (range, 9 to 36 months) that was successfully treated with a further 20-mg dose increment for a mean period of 36 months (range, 6 to 39 months). Median gastrin levels increased initially from 60 ng/L before study entry to 162 ng/L (P < 0.01) with treatment and reached a plateau during maintenance treatment. Very high gastrin levels (> 500 ng/L) were observed in a subgroup (11%) of patients. The incidence of micronodular hyperplasia increased from 2.5% of the patients at first biopsy to 20% at the last biopsy (P = 0.001), with a corresponding progression of gastritis to subatrophic or atrophic gastritis from less than 1% to 25% (P < 0.001), which was more pronounced in patients with very high serum gastrin levels. CONCLUSIONS: Maintenance therapy with omeprazole was effective for at least 5 years in patients with gastroesophageal reflux disease resistant to treatment with H2-receptor antagonists. Treatment was accompanied by a persistent increase in serum gastrin levels and an increase of micronodular argyrophil cell hyperplasia and subatrophic or atrophic gastritis.

Omeprazole and high dose ranitidine in the treatment of refractory reflux oesophagitis.

Thirty two consecutive patients (age range 6 months-13.4 years) with severe reflux oesophagitis were randomised to a therapeutic trial for eight weeks during which they received either standard doses of omeprazole (40 mg/day/1.73 m2 surface area) or high doses of ranitidine (20 mg/kg/day). Twenty five patients completed the trial (12 on omeprazole, 13 on ranitidine). At entry and at the end of the trial patients underwent symptomatic score assessment, endoscopic and histological evaluation of the oesophagus, and simultaneous oesophageal and gastric pH measurement; results are given as median (range). Both therapeutic regimens were effective in decreasing clinical score (omeprazole before 24.0 (15-33), after 9.0 (0-18); ranitidine before 19.5 (12-33), after 9.0 (6-12)), in improving the histological degree of oesophagitis (omeprazole before 8.0 (6-10), after 2.0 (0-60); ranitidine before 8.0 (8-10), after 2.0 (2-6), and in reducing oesophageal acid exposure, measured as minutes of reflux at 24 hour pH monitoring (omeprazole before 129.4 (84-217), after 44.6 (0.16-128); ranitidine before 207.3 (66-306), after 58.4 (32-128)) as well as intragastric acidity, measured as median intragastric pH (omeprazole before 2.1 (1.0-3.0), after 5.1 (2.2-7.4); ranitidine before 1.9 (1.6-4), after 3.4 (2.3-5.3)). Serum gastrin concentration was > 150 ng/l in four patients on omeprazole and in three patients on ranitidine. It is concluded that in children with refractory reflux oesophagitis high doses of ranitidine are comparable with omeprazole for the healing of oesophagitis and relief of symptoms; both drugs resulted in efficacious reduction of intragastric acidity and intra-oesophageal acid exposure.