Association Between Vonoprazan and the Risk of Gastric Cancer After Helicobacter pylori Eradication.

BACKGROUND & AIMS: Potassium-competitive acid blockers (PCABs) have been increasingly used to treat upper gastrointestinal disorders, replacing proton pump inhibitors (PPIs). Whereas PPIs are associated with an increased risk of gastric cancer (GC) after Helicobacter pylori (Hp) eradication, it is uncertain whether PCABs carry the same risk. METHODS: Using a population-based claims database in Japan, we identified patients who were prescribed a clarithromycin-based first regimen of Hp eradication between 2015 and 2018. Patients who failed this regimen and those diagnosed with GC before or within 1 year after Hp eradication were excluded. We compared GC incidence between PCAB users and histamine type-2 receptor antagonist (H2RA) users, matching them on the basis of propensity scores calculated with considerations for age, sex, smoking, alcohol consumption, comorbidities, and co-administered medications. PCABs included only vonoprazan in this study. RESULTS: Among 54,055 patients, 568 (1.05%) developed GC during the follow-up period (mean, 3.65 years). The cumulative incidence of GC was 1.64% at 3 years, 2.02% at 4 years, and 2.36% at 5 years in PCAB users and 0.71% at 3 years, 1.04% at 4 years, and 1.22% at 5 years in H2RA users. The use of PCABs was associated with a higher GC risk (matched hazard ratio, 1.92; 95% confidence interval, 1.13-3.25; P = .016). Longer PCAB use and high-dose PCAB use were significantly associated with higher incidence of GC. Sensitivity analyses showed the risk of GC incidence among PCAB users was comparable with that of PPI users. CONCLUSIONS: The use of PCABs was associated with an increased risk of GC among Hp-eradicated patients, with duration/dose response effects.

Efficacy and safety of combination of curcuminoid complex and diclofenac versus diclofenac in knee osteoarthritis: A randomized trial.

BACKGROUND: To compare the efficacy and safety of combination of curcuminoid complex and diclofenac vs diclofenac alone in the treatment of knee osteoarthritis (OA). METHODS: In this randomized trial, 140 patients of knee OA received either curcuminoid complex 500 mg (BCM-95) with diclofenac 50 mg 2 times daily or diclofenac 50 mg alone 2 times daily for 28 days. Patients were assessed at baseline, day 14 and day 28. Primary efficacy measures were Knee injury and OA outcome score (KOOS) subscale at day 14 and day 28. Anti-ulcer effect and patient-physician's global assessment of therapy at day 28 were included as secondary endpoints. Safety after treatment was evaluated by recording adverse events and laboratory investigations. RESULTS: Both treatment groups showed improvement in primary endpoints at each evaluation visit. Patients receiving curcuminoid complex plus diclofenac showed significantly superior improvement in KOOS subscales, viz. pain and quality of life at each study visit (P < .001) when compared to diclofenac. Less number of patients required rescue analgesics in curcuminoid complex plus diclofenac group (3%) compared to diclofenac group (17%). The number of patients who required histamine 2 (H2) blockers was significantly less in curcuminoid complex plus diclofenac group compared to diclofenac group (6% vs 28%, respectively; P < .001). Adverse effects were significantly less in curcuminoid complex plus diclofenac group (13% vs 38% in diclofenac group; P < .001). Patient's and physician's global assessment of therapy favored curcuminoid complex plus diclofenac than diclofenac. CONCLUSION: Combination of curcuminoid complex and diclofenac showed a greater improvement in pain and functional capacity with better tolerability and could be a better alternative treatment option in symptomatic management of knee OA. TRIAL REGISTRATION: ISRCTN, ISRCTN10074826.

Consumption of medicines used for gastric acid-related disorders in Australia and South Korea: a cross-country comparison.

PURPOSE: The study's aim was to compare the use of proton pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RAs) and mucoprotective medicines (MPs) used for gastric acid-related disorders (GARD) in Australia and South Korea (Korea) from 2004 to 2017. METHODS: Prescription data for PPIs, H2RAs and MPs for Australian outpatients were extracted from the Australian Statistics on Medicines annual reports, with dose-specific and expenditure data obtained from Medicare. Similar data were obtained from Korean National Health Insurance Service claims data. We analysed the volume and expenditure of medicines use annually using the defined daily dose per 1,000 population per day. We calculated which medicines accounted for 90% of use and estimated the proportions of use for low- and high-dose PPIs. RESULTS: While total utilisation for GARD medicines increased over time in both countries, patterns of use differed. Overall, use was somewhat higher in Australia but increased more rapidly in Korea. PPIs were used more extensively in Australia, while more MPs and H2RAs were used in Korea. Expenditure and use of low-dose PPIs is escalating in Korea. CONCLUSION: There were substantial differences in the use of GARD medicines in Australia and Korea over 14 years. Both countries face similar challenges to promote rational medicines use and contain medical care costs. The discrepant prescribing patterns can be attributed to differences in healthcare systems, pharmaceutical policies and demographics. This study provides a baseline to influence more rational use of these medicines. It provides insight into medicines policies for other countries that face similar challenges.

Influence of oral magnesium-containing supplement and antacid administration on hypomagnesemia induced by panitumumab.

PURPOSE: Hypomagnesemia is a common side effect of panitumumab. The effect of magnesium-containing supplement as a laxative and concomitant antacid (proton pump inhibitor and histamine H2 antagonist) administration on panitumumab-induced hypomagnesemia was retrospectively investigated. METHODS: Patients with advanced or recurrent colorectal cancer who received panitumumab were included in this study. Serum magnesium levels were extracted from the electronic medical records of 1753 administrations in 221 patients who received panitumumab. Serum magnesium levels in patients with or without oral magnesium-containing supplement and antacid treatment were compared using analysis of covariance as the number of panitumumab administration up to 16 times for covariates. RESULTS: The mean serum magnesium levels were significantly decreased with increasing number of panitumumab administrations (2.13 mg/dL at 1st vs. 1.55 mg/dL at 16th, p < 0.001). The use of oral magnesium-containing supplement significantly inhibited the decline in mean serum magnesium level (1.98 mg/dL vs. 1.78 mg/dL, p < 0.001). However, antacid use in patients receiving oral magnesium-containing supplement significantly decreased the effectiveness of the magnesium supplement on serum magnesium level (2.02 mg/dL vs. 1.93 mg/dL, p < 0.05). CONCLUSION: The use of oral magnesium-containing supplement might function as magnesium supplement based on the finding that use of oral magnesium-containing supplement during panitumumab administration decreased hypomagnesemia. However, combination of antacid decreased the supplemental effect of oral magnesium on hypomagnesemia. These results suggest the possibility that use of antacids during anti-EGFR antibody administration may promote hypomagnesemia.

An Analysis of the Inclusion of Medications Considered Potentially Inappropriate in Older Adults in Chemotherapy Templates for Hematologic Malignancies: One Recommendation for All?

BACKGROUND: There remains a paucity of data regarding the use of potentially inappropriate medications (PIMs) in the supportive management of older adults undergoing chemotherapy. Raising awareness among healthcare providers regarding the frequency of their use and potential toxicities may help to minimize the risks to patients. OBJECTIVE: The aim of this study was to evaluate the frequency of six specific classes of medications considered PIMs by the American Geriatrics Society Beers Criteria that are commonly included in the National Comprehensive Cancer Network (NCCN) chemotherapy order templates for hematologic malignancies. The six PIMs evaluated are first-generation antihistamines, benzodiazepines, corticosteroids, H2-receptor antagonists, metoclopramide, and antipsychotics. METHODS: A total of 311 unique chemotherapy order templates published online by the NCCN for the treatment of hematologic malignancies were reviewed to determine the frequency that these six specific PIMs were recommended for supportive care. RESULTS: Approximately 45% of the NCCN chemotherapy templates for hematologic malignancies specifically recommended the use of at least one of the six PIMs examined. The remainder of the templates evaluated referred exclusively to the NCCN Guidelines® on Oncology for Antiemesis, which also included the use of at least one of the six PIMs evaluated. CONCLUSIONS: These findings demonstrate that PIMs are frequently used as supportive therapy in the treatment of hematologic malignancies. Increasing healthcare provider awareness of their potential side effects may minimize the risks associated with their use in older adults with hematologic malignancies undergoing chemotherapy.

[The novel approaches to the rehabilitation of the patients presenting with gastroesophageal reflux disease and co-morbid pathology]. / Novye podkhody k reabilitatsii bol'nykh gastroézofageal'noi refliuksnoi bolezn'iu s komorbidnoi patologiei.

This paper was designed to discuss the problems of co-morbidity and approaches to the rehabilitation of the patients presenting with gastroesophageal reflux disease and a concomitant pathology and to analyze the issues concerning the possible vertebro-visceral correlations inherent in the diseases of the internal organs. AIM: To evaluate the vertebro-neurological status of the thoracic segment of the vertebral column in the patients suffering from gastroesophageal reflux disease and to further improve the methods for their treatment taking into consideration the concomitant pathology, if any. MATERIAL AND METHODS: A total of 290 patients at the age varying from 25 to 60 (mean 44,3±11,3) years with the non-erosive form of gastroesophageal reflux disease were examined in the phase of its exacerbation. They included 132 (45.5%) men and 158 (54.5%) women. The duration of the disease averaged 13.1±3.3 years and that of the exacerbation period 1.2±0.5 months. All the patients underwent the vertebro-neurological examination. The visual analog scale was used to obtain the subjective characteristics of the pain syndrome associated with thoracalgia The quality of life of the patients was estimated based on the Medical Outcomes Study Short Form-36 (scores of MOS SF-36). To evaluate the effectiveness of the proposed approach to the treatment of the gastroesophageal reflux disease, the 260 participants of the study were randomly allocated to two groups, the main and control ones. The latter group was comprised of 130 patients given the standard treatment including the use of histamine H2-receptor antagonists, proton pump inhibitors, stimulators of the motility of the gastrointestinal tract, alginates, and other drugs, as indicated. The former group consisted of the remaining 130 patients undergoing the standard course of pharmacopuncture to correct the functional disorders in the thoracic segment of the vertebral column. The medications of choice for the purpose were the anti-homotoxic agents, such as placental compositum, co-enzyme compositum, and ubichinon compositum (Biologische Heilmittel Heel GmbH, Germany). The statistical analysis was performed with the use of the non-parametric methods based on the Statistica application software package ('StatSoft Inc.', США). RESULTS: The present article reports the results of the study that demonstrate significant strong positive correlation between the clinical manifestations of gastroesophageal reflux disease (the frequency and severity of symptoms) and thoracalgia and provides a rationale for the assessment of the vertebro-neurological status of the thoracic spine in the patients exhibiting the clinical signs of gastroesophageal reflux disease. The study substantiated the inclusion of pharmacopuncture with placenta compositum, co-enzyme compositum, and ubichinon compositum anti-homotoxic medications in the complex rehabilitation programs for the patients presenting with the clinical signs of gastroesophageal reflux disease and the concomitant thoracalgia symptoms. To assess the effectiveness of the proposed method for the treatment of this condition, such diagnostic criteria as the vertebro-neurological symptoms, coefficient of the thoracalgia-associated pain syndrome, the frequency and intensity of the gastroesophageal reflux disease symptoms, and the quality of life parameters were used. CONCLUSION: The results of the present study provide strong evidence that pharmacopuncture helps to improve the quality of life of the patients, alleviate thoracalgia symptoms and clinical signs of gastroesophageal reflux disease, and reduce the intensity of the pain syndrome caused by thoracalgia.

Current and future therapies for the treatment of histamine-induced angioedema.

INTRODUCTION: Angioedema, a sudden, self-limited swelling of localized areas of any part of the body that may or may not be associated with urticaria, is thought to be the result of a mast-cell mediated process versus a bradykinin etiology. Understanding the mechanism is key in determining the proper treatment. Areas Covered: Clinical presentation of varying angioedema types may be similar; however, the appropriate treatment algorithm is dependent upon clinicians' knowledge of the underlying pathophysiology and classification of angioedema. Literature review of recent guidelines, available medications, and alternative therapies was completed to provide an overview of options. CONCLUSION: There are no formal guidelines for treatment of acute or chronic histamine-mediated angioedema, and therefore, algorithms for the treatment of acute and chronic urticaria should be followed until such information becomes available. Differentiating histamine-mediated versus bradykinin mediated angioedema is essential, as treatments and treatment responses are quite different. Further research is needed to better understand idiopathic angioedema that is unresponsive to H1/H2 antagonists, LTMAs, or medications designed to treat bradykinin-mediated angioedema.

Design and optimization of a chronotherapeutic dosage form for treatment of nocturnal acid breakthrough.

OBJECTIVE: Present work focuses on the use of tamarind gum to develop a drug delivery system making combined use of floating and pulsatile principles, for the chrono-prevention of nocturnal acid breakthrough. METHOD: The desired aim was achieved by fabricating a floating delivery system bearing time - lagged coating of Tamarindus indica seed polymer for the programmed release of Famotidine. Response Surface METHODology was the statistical tool that was employed for experiment designing, mathematical model generation and optimization study. A 32 full factorial design was used in designing the experiment. % weight ratio of tamarind gum to ethyl cellulose in the coating combination and the coating weight were the independent variables, whereas the lag time for drug release and the cumulative % drug release in 330 minutes were the observed responses. KEY FINDINGS: Results revealed that both the coating composition and the coating weight significantly affected the release of drug from the dosage form. CONCLUSION: The optimized formulation prepared according to the computer generated software, Design-Expert® deciphered response which were in close proximity with the experimental responses, thus confirming the robustness and accuracy of the predicted model for the utilization of natural polymer like tamarind gum for the chronotherapeutic treatment of nocturnal acid breakthrough.

Double liposomes mediated dual drug targeting for treatment of Helicobacter pylori infections.

In the present study the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Histamine-2 receptor antagonist use and incident dementia in an older cohort.

OBJECTIVES: To examine whether histamine-2 receptor antagonist medications (H2RAs) are associated with a lower incidence of all-cause dementia or Alzheimer's disease (AD), as some studies have suggested. DESIGN: Prospective population-based cohort SETTING: Group Health, an integrated health maintenance organization, Seattle, Washington. PARTICIPANTS: Two thousand nine hundred twenty-three participants aged 65 and older without dementia at baseline, with initial recruitment between 1994 and 1996. MEASUREMENTS: Follow-up occurred every 2 years to identify incident dementia and AD using standard criteria. Exposure to H2RAs was determined based on automated pharmacy data. Three aspects of exposure (time-varying) were examined based on standard daily dose (SDD): cumulative use, intensity of use (highest SDD in any prior 2-year window), and cumulative use stratified according to recency (1-3 years vs >3 years before). RESULTS: Over a mean follow-up of 6.7 years, 585 subjects developed dementia (453 developed AD). Total cumulative exposure was not associated with dementia (P=.35; omnibus test) or AD (P=.23). The adjusted hazard ratios for the highest exposure category (>1,080 SDDs) compared with light or no use were 1.28 (95% confidence interval (CI)=0.95-1.72) for dementia and 1.41 (95% CI=1.00-1.97) for AD. Intensity of use was not associated with dementia (P=.39) or AD (P=.63). Examining exposure according to recent and distant cumulative use also showed no association with dementia (P=.11) or AD (P=.30). CONCLUSION: No association was found between H2RA use and risk of all-cause dementia or AD using more-detailed and -extensive information about past H2RA use than any prior study.

Statistical optimization of ranitidine HCl floating pulsatile delivery system for chronotherapy of nocturnal acid breakthrough.

Present work conceptualizes a specific technology, based on combining floating and pulsatile principles to develop drug delivery system, intended for chronotherapy in nocturnal acid breakthrough. This approach will be achieved by using a programmed delivery of ranitidine hydrochloride from a floating tablet with time-lagged coating. In this study, investigation of the functionality of the outer polymer coating to predict lag time and drug release was statistically analyzed using the response surface methodology (RSM). RSM was employed for designing of the experiment, generation of mathematical models and optimization study. The chosen independent variables, i.e. percentage weight ratios of ethyl cellulose to hydroxypropyl methyl cellulose in the coating formulation and coating level (% weight gain) were optimized with a 3(2) full factorial design. Lag time prior to drug release and cumulative percentage drug release in 7h were selected as responses. Results revealed that both, the coating composition and coating level, are significant factors affecting drug release profile. A second-order polynomial equation fitted to the data was used to predict the responses in the optimal region. The optimized formulation prepared according to computer-determined levels provided a release profile, which was close to the predicted values. The proposed mathematical model is found to be robust and accurate for optimization of time-lagged coating formulations for programmable pulsatile release of ranitidine hydrochloride, consistent with the demands of nocturnal acid breakthrough.

Acid-suppressive medications and risk of bone loss and fracture in older adults.

Recent studies have suggested an increased fracture risk with acid-suppressive medication use. We studied two cohorts of men and women over age 65 who were enrolled in the Osteoporotic Fractures in Men Study (MrOS) and the Study of Osteoporotic Fractures (SOF), respectively. We used dual-energy X-ray absorptiometry and assessed baseline use of proton pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs) in 5,755 men and 5,339 women. Medication use and bone mineral density (BMD) were assessed, and hip and other nonspine fractures were documented. On multivariate analysis, men using either PPIs or H2RAs had lower cross-sectional bone mass. No significant BMD differences were observed among women. However, there was an increased risk of nonspine fracture among women using PPIs (relative hazard [RH] = 1.34, 95% confidence interval [CI] 1.10-1.64). PPI use was also associated with an increased risk of nonspine fracture in men but only among those who were not taking calcium supplements (RH = 1.49, 95% CI 1.04-2.14). H2RA use was not associated with nonspine fractures, and neither H2RA use nor PPI use was associated with incident hip fractures in men or women. The use of PPIs in older women, and perhaps older men with low calcium intake, may be associated with a modestly increased risk of nonspine fracture.

Do acid-lowering agents affect vitamin B12 status in older adults?

OBJECTIVE: To examine the relationship between serum vitamin B12 levels in older adults on histamine(2) receptor antagonists (H2 blockers) or proton-pump inhibitors (PPI) over 6 years. PARTICIPANTS: A cross-sectional sample of 659 adults, 60 to 102 years, from long-term care facilities and community ambulatory care (C) in the Bronx. MEASUREMENTS: Patient demographics, serum B12 levels, use and duration of use of H2 blockers, PPIs, antacids, multivitamin/minerals, liquid dietary supplements, oral vitamin B12 supplementation, oral or intramuscular B12 therapy, and recent lab chemistries. RESULTS: Acid-lowering agents (ALA) were used by 54% (PPIs by 26% and H2 blockers by 28%), duration averaged 18.2 +/- 16.0 (SD) months. NH and C subjects had similar ages (P = .9971), gender distributions (P = .625), durations of ALA use (P = .1227), and rates of PPI use (P = .130); NH subjects used more H2 blockers (P < .0005) and had less low B12 status (P = .037). H2 blocker use did not influence serum B12 status (P = .1036) while PPI use was associated with diminished serum B12 levels (P < .00005). Concomitant oral B12 supplementation slowed but did not prevent the decline in B12 status during prolonged PPI use (P = .0125). CONCLUSIONS: B12 status declines during prolonged PPI use in older adults, but not with prolonged H2 blocker use; supplementation with RDA amounts of B12 do not prevent this decline. This report reinforces that B12 deficiency is common in the elderly and suggests that it appears prudent to monitor periodically B12 status while on prolonged PPI use, to enable correction before complications ensue.

Long-term proton pump inhibitor therapy and risk of hip fracture.

CONTEXT: Proton pump inhibitors (PPIs) may interfere with calcium absorption through induction of hypochlorhydria but they also may reduce bone resorption through inhibition of osteoclastic vacuolar proton pumps. OBJECTIVE: To determine the association between PPI therapy and risk of hip fracture. DESIGN, SETTING, AND PATIENTS: A nested case-control study was conducted using the General Practice Research Database (1987-2003), which contains information on patients in the United Kingdom. The study cohort consisted of users of PPI therapy and nonusers of acid suppression drugs who were older than 50 years. Cases included all patients with an incident hip fracture. Controls were selected using incidence density sampling, matched for sex, index date, year of birth, and both calendar period and duration of up-to-standard follow-up before the index date. For comparison purposes, a similar nested case-control analysis for histamine 2 receptor antagonists was performed. MAIN OUTCOME MEASURE: The risk of hip fractures associated with PPI use. RESULTS: There were 13,556 hip fracture cases and 135,386 controls. The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI therapy was 1.44 (95% confidence interval [CI], 1.30-1.59). The risk of hip fracture was significantly increased among patients prescribed long-term high-dose PPIs (AOR, 2.65; 95% CI, 1.80-3.90; P<.001). The strength of the association increased with increasing duration of PPI therapy (AOR for 1 year, 1.22 [95% CI, 1.15-1.30]; 2 years, 1.41 [95% CI, 1.28-1.56]; 3 years, 1.54 [95% CI, 1.37-1.73]; and 4 years, 1.59 [95% CI, 1.39-1.80]; P<.001 for all comparisons). CONCLUSION: Long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.

Review article: putting immediate-release proton-pump inhibitors into clinical practice--improving nocturnal acid control and avoiding the possible complications of excessive acid exposure.

Nocturnal gastro-oesphageal reflux is an under-appreciated clinical challenge. This condition may cause symptoms such as nocturnal heartburn, or it may be asymptomatic. In addition, patients may experience sleep disturbances that can potentially lead to complications such as erosive oesophagitis and Barrett's oesophagus, and may be a risk factor for development of oesophageal adenocarcinoma. Delayed-release proton-pump inhibitors (PPIs) have traditionally been effective in treating both daytime and night-time reflux symptoms, but are limited in control of nocturnal acidity by their pharmacodynamic characteristics. This narrative review addresses the prevalence, impact and pharmacologic approaches used to control nocturnal acidity. Methods to optimize nocturnal acid control include careful attention to dosing schedule, using higher doses of PPIs, adding an histamine H2-receptor antagonist at bedtime to once or twice daily delayed-release PPI, or using immediate-release omeprazole (Zegerid powder for oral suspension; Santarus, Inc., San Diego, CA, USA). This new formulation appears to provide sustained control of intragastric pH at steady state, and when dosed at bedtime, and may be effective in improving control of nocturnal pH and treating night-time GERD.

Effects of Momordica charantia L. (Cucurbitaceae) on indomethacin-induced ulcer model in rats.

BACKGROUND/AIMS: Fruits of Momordica charantia L.-cucurbitaceae have been frequently used in folk medicine for rapid healing of cutaneous lesions and peptic ulcer, especially in Western Anatolia in Turkey. METHODS: The anti-ulcerogenic effect of the oily extract of Momordica charantia fruits was investigated in male Sprague-Dawley rats. Animals were separated into six groups. Distilled water (control group), famotidine (40 mg/kg), oily extracts (5 and 10 ml/kg), and vehicles (olive oil -5 and 10 ml/kg) were given orally (gavage). Thirty minutes later indomethacin (25 mg/kg) was administrated to all the groups. Six hours later, animals were killed with decapitation. For each stomach, ulcerated and total areas were measured (mm2). The ulcer indexes for each stomach and the ulcer inhibition rates for each group were calculated, after which the stomachs were evaluated pathologically (polymorphonuclear leukocytes infiltration). RESULTS: Ulcer inhibition rates were as follows: famotidine -91.54%, oily extract (5 ml/kg) -53.80%, oily extract (10 ml/kg) -98.04%, vehicle (olive oil -5 ml/kg) -18.40%, and vehicle (olive oil -10 ml/kg) -88.02%. According to polymorphonuclear leukocytes infiltration, oily extract (10 ml/kg) and vehicle (10 ml/kg) had similar effects to famotidine. CONCLUSIONS: The olive oil extract of M. charantia fruit did show a protective effect macroscopically.

The efficacy of omeprazole twice daily with supplemental H2 blockade at bedtime in the suppression of nocturnal oesophageal and gastric acidity.

BACKGROUND: It has been presumed that nocturnal acid breakthrough may pose a risk for the development of nocturnal gastro-oesophageal reflux. AIM: To investigate the occurrence of gastro-oesophageal reflux and acid breakthrough during polygraphically monitored sleep under conditions of powerful acid suppression with omeprazole 20 mg b.d. and an additional dose of ranitidine at bedtime. METHODS: Nineteen individuals with symptomatic gastro-oesophageal reflux disease were studied. Each individual was studied on two occasions subsequent to 1 week of 20 mg of omeprazole treatment b.d. Subjects underwent 24-h oesophageal and gastric pH recording, with polysomnographic monitoring. Participants received either 150 mg ranitidine at bedtime or placebo, prior to a provocative meal. RESULTS: Ranitidine administration resulted in a significant (P < 0.01) reduction in the percentage of time the intragastric pH < 4.0. There was no significant difference with regard to measures of gastro-oesophageal reflux, and reflux events were not noted to occur with a significantly greater frequency during periods of nocturnal acid breakthrough compared with control intervals without acid breakthrough. CONCLUSIONS: The administration of 150 mg ranitidine at bedtime did not significantly alter the occurrence of sleep-related gastro-oesophageal reflux.