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Parkinson's disease (PD) is often managed with L-3,4-dihydroxyphenylalanine (L-DOPA), which is still the gold standard to relieve the clinical motor symptoms of PD. However, chronic use of L-DOPA leads to significant motor complications, especially L-DOPA-induced dyskinesia (LID), which limit the therapeutic benefit. Few options are available for the pharmacological management of LID partly due to the inadequacy of our mechanistic understanding of the syndrome. We focused on the role of the histamine (HA) H2 receptor (H2R) in the striatum, which others have shown to be involved in the development of LID. We generated LID in a hemiparkinsonian mouse model and tested the signaling effects of ranitidine, an H2R antagonist. We used histidine decarboxylase deficient mice (Hdc-Ko) which lacks HA to study the role of G-protein-coupled receptor kinases (GRKs) in HA deficiency. Loss of HA in Hdc-Ko mice did not result in the downregulation of GRKs, especially GRK3 and GRK6, which were previously found to be reduced in hemiparkinsonian animal models. Ranitidine, when given along with L-DOPA, normalized the expression of GRK3 in the dopamine-depleted striatum thereby inhibiting LID in mice. The extracellular signal regulated kinase and ΔFosB signaling pathways were attenuated in the lesioned striatum when ranitidine was combined with L-DOPA than L-DOPA alone. These results demonstrate that ranitidine inhibits LID by normalizing the levels of GRK3, extracellular signal regulated kinase activation, and FosB accumulation in the dopamine-depleted striatum via HA H2R antagonism., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Since the treatment of gastroesophageal reflux disease (GERD) symptoms in children is of the utmost importance, the current study is aimed to evaluating the efficacy of quince syrup and ranitidine in the management of pediatric patients with symptomatic GERD., Methods and Materials: This double-blind, randomized clinical trial was performed on 96 children suspected of suffering from GERD. The patients referred to the gastrointestinal clinic of Ghaem Hospital, Iran, during 2017. The participants were randomly categorized into two groups (ranitidine and ranitidine plus quince syrup). The GERD symptoms, including the severity and frequency of vomiting, refusal of eating, difficulty in swallowing, choking at the time of eating, burping or belching, and abdominal or belly pain, were gathered before and after the intervention (4 weeks) using standardized Global Severity Questionnaire (GSQ-YC)., Results: The comparison of two groups in terms of vomiting, refusal of eating, burping or belching, and abdominal or belly pain showed a significant difference 4 and 6 weeks after the intervention (P< 0.05). However, the comparison of difficulty in swallowing and choking at the time of eating between the two groups showed that there was no significant difference after 2, 4, and 6 weeks of the intervention (P > 0.05). The comparison of the total scores between the two groups showed that there was a significant difference 2 (17.8 ± 2.6 vs 23.4 ± 4.0; P < 0.05), 4 (11.5 ± 2.3 vs 18.8 ± 3.6; P< 0.05), and 6 (12.2 ± 2.3 vs 21.1 ± 4.1; P<  0.05) weeks after the intervention., Conclusion: The results showed that the administration of ranitidine plus quince syrup was useful to improve pediatric GERD. However, it is recommended to conduct the future studies with a larger sample size and different dosage., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There is a need to find/discover novel leads to treat complex and/or multi-factorial-pathogenic disease(s) like Nonsteroidal anti-inflammatory drugs (NSAID)-induced gastroenteropathy or gastrointestinal (GI) toxicity as it has emerged as an important medical and socioeconomic problem. There is no approved therapeutic strategy to prevent NSAID-induced enteropathic damage and highly effective gastro-protective drugs such as ranitidine hydrochloride (RAN) exacerbate it. In this purview, the multi target drug discovery approach (MTDD), combination approach and hit to lead strategies based on the foundation of ethnopharmacology and/or reverse pharmacology holds strong potential. Hence, the primary objectives of the current study were to explore the mechanism behind the preventative/curative effects of quercetin (QCT) on RAN exacerbated diclofenac sodium (DIC)-induced enteropathic damage and to assess the effects of co-administration of QCT and RAN on DIC-induced gastropathic damage in rats. Rats were treated twice daily with QCT (35, 50 and 100 mg kg -1 PO) and/or RAN (15 mg kg -1 PO) or vehicle for a total of 10 days. In some experiments, DIC (9 mg kg -1 ) was administered orally twice daily for the final 5 days of RAN/QCT + RAN/vehicle administration. Rats in all the groups were fasted after the last dose on 9th day (free access to water). 12 h after the last dose on 10th day, rats were euthanized and their GI tracts were assessed for haemorrhagic damage, alteration in xanthine oxidase (XO) activity, lipid peroxidation, intestinal permeability and GI luminal pH alterations along with haematological and biochemical estimations. The macroscopic, haematological, biochemical and histological evidences suggested that, though, RAN prevented the DIC-induced gastric injury, it exacerbated enteropathic damage. However, QCT not only significantly attenuated the RAN-induced exacerbation of enteropathic damage caused by DIC at the doses of 50 and 100 mg kg -1 , but, this combination provided complete GI safety against the toxic effects of DIC too. The mechanisms behind the gastro-enteroprotective ability of QCT may be related to its ability to inhibit XO activity thus, preventing enhanced oxidative stress on GI tissues, prevent lipid peroxidation, IP alteration and alteration in GI luminal pH. The preventative effects of QCT on NSAID-induced gastroenteropathy were ably supported by the QCT induced prevention of GI blood loss and serum protein loss. These pharmaco-mechanistic results of QCT are aligning to combination based MTDD approach and hence we propose it as a promising lead to treat NSAID-gastroenteropahty and related complications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In the stomach of a gastric ulcer patient who had been administered an anti-acid, a gram-negative and urease-negative bacillus similar in size to Helicobacter pylori was infected together with H. pylori. According to biochemical test and 16S rRNA gene analysis, the urease-negative bacterium was identified as Kingella denitrificans, a human nasopharyngeal commensal. In contrast to the standard strain of K. denitrificans, the isolate showed catalase activity, did not produce acid from glucose, and exhibited acid tolerance. Acid tolerance of H. pylori was increased by cocultivation with the K. denitrificans isolate, but not with other isolates of K. denitrificans. Disruption of physiological and immunological niche by dysbiotic colonization of bacterium may provide pathological attributes to human stomach. Collectively, a careful administration of anti-acids to the elderly, especially those with atrophic gastritis, is necessary to avoid repression of the gastric barrier to bacteria., (Copyright © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Epidemiologic and physiologic studies suggest an association between gastroesophageal reflux disease (GERD) and chronic cough. However, the benefit of antireflux therapy for chronic cough remains unclear, with most relevant trials reporting negative findings. This systematic review aimed to reevaluate the response of chronic cough to antireflux therapy in trials that allowed us to distinguish patients with or without objective evidence of GERD., Methods: PubMed and Embase systematic searches identified clinical trials reporting cough response to antireflux therapy. Datasets were derived from trials that used pH-metry to characterize patients with chronic cough., Results: Nine randomized controlled trials of varied design that treated patients with acid suppression were identified (eight used proton pump inhibitors [PPIs], one used ranitidine). Datasets from two crossover studies showed that PPIs significantly improved cough relative to placebo, albeit only in the arm receiving placebo fi rst. Therapeutic gain in seven datasets was greater in patients with pathologic esophageal acid exposure (range, 12.5%-35.8%) than in those without (range, 0.0%-8.6%), with no overlap between groups., Conclusions: A therapeutic benefit for acid-suppressive therapy in patients with chronic cough cannot be dismissed. However, evidence suggests that rigorous patient selection is necessary to identify patient populations likely to be responsive, using physiologically timed cough events during reflux testing, minimal patient exclusion because of presumptive alternative diagnoses, and appropriate power to detect a modest therapeutic gain. Only then can we hope to resolve this vexing clinical management problem.

Background: Use of proton-pump inhibitors (PPIs) is common in patients on dual antiplatelet therapy (DAT). Recent warnings about potential interactions of PPIs with clopidogrel metabolism leading to impaired DAT efficacy has prompted the recommendation of substituting PPIs with H(2)-receptor antagonists such as ranitidine. We investigated whether ranitidine interacts with P2Y(12) inhibition on the platelet level., Methods: Blood was collected from 15 patients with stable coronary artery disease, who had undergone elective coronary intervention. Clopidogrel responsiveness was assessed 24h after the administration of a 600mg loading dose using the P2Y(12) specific platelet-reactivity-index (PRI) and light-transmittance aggregometry in the presence and absence of a pharmacologically relevant concentration of the H(2)-receptor antagonist ranitidine (400ng/ml)., Results: Adding ranitidine enhanced P2Y(12)-mediated platelet reactivity to ADP assessed by the PRI (mean PRI+/-SEM: before ranitidine 28+/-5%; after ranitidine 37+/-5%, p=0.0025). Similarly, prostaglandin E1 (PGE(1))-mediated inhibition of ADP-induced aggregation was abrogated in the presence of ranitidine (Agg(max)+/-SEM: before PGE(1) 41+/-2%; after PGE(1) 29+/-2%, p<0.01 vs. before PGE(1); after PGE(1)+ranitidine 42+/-2%, p<0.01 vs. after PGE(1))., Conclusions: Exposition of platelets with ranitidine significantly enhanced their responsiveness to ADP and contributed to impaired P2Y(12) inhibition suggesting that ranitidine interacts with clopidogrel efficacy through adenylyl cyclase inhibition on the platelet level., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Maternal haemodynamic changes and neonatal well-being following bolus administration of ephedrine and phenylephrine were compared in 60 term parturients undergoing elective caesarean delivery under spinal anaesthesia., Methods: In a randomised double-blind study, women received boluses of either ephedrine 6 mg (group E; n=30) or phenylephrine 100 microg (group P; n=30) whenever maternal systolic pressure was 80% of baseline., Results: Changes in systolic pressure were comparable in the two groups. There were no differences in the incidence of bradycardia (group E: 0% vs. group P: 16.7%; P>0.05), nausea (group E: 13% vs. group: P 0; P>0.05) and vomiting (group E: 3.3% vs. group P: 0; P>0.05). Umbilical artery (UA) pH (group E: 7.29 +/- 0.04 vs. group P: 7.32 +/- 0.04; P=0.01) and venous pH (group E: 7.34 +/- 0.04 vs. group P: 7.38 +/- 0.05; P=0.002) were significantly greater in group P than in group E. UA base excess was significantly less in group E (-2.83 +/- 0.94 mEq/L) than in group P (-1.61 +/- 1.04 mEq/L; P<0.001). Apgar scores at 1, 5 and 10min and neurobehavioural scores at 2-4 h, 24 h and 48 h were similar in the two groups (P>0.05)., Conclusions: Phenylephrine 100 mug and ephedrine 6 mg had similar efficacy in the treatment of maternal hypotension during spinal anaesthesia for elective caesarean delivery. Neonates in group P had significantly higher umbilical arterial pH and base excess values than those in group E, which is consistent with other studies., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Stress ulcer prophylaxis (SUP) using ranitidine, a histamine H2 receptor antagonist, has been associated with an increased risk of ventilator-associated pneumonia. The proton pump inhibitor (PPI) pantoprazole is also commonly used for SUP. PPI use has been linked to an increased risk of community-acquired pneumonia. The objective of this study was to determine whether SUP with pantoprazole increases pneumonia risk compared with ranitidine in critically ill patients., Methods: The cardiothoracic surgery database at our institution was used to identify retrospectively all patients who had received SUP with pantoprazole or ranitidine, without crossover between agents. From January 1, 2004, to March 31, 2007, 887 patients were identified, with 53 patients excluded (pantoprazole, 30 patients; ranitidine, 23 patients). Our analysis compared the incidence of nosocomial pneumonia in 377 patients who received pantoprazole with 457 patients who received ranitidine., Results: Nosocomial pneumonia developed in 35 of the 377 patients (9.3%) who received pantoprazole, compared with 7 of the 457 patients (1.5%) who received ranitidine (odds ratio [OR], 6.6; 95% confidence interval [CI], 2.9 to 14.9). Twenty-three covariates were used to estimate the probability of receiving pantoprazole as measured by propensity score (C-index, 0.77). Using this score, pantoprazole and ranitidine patients were stratified according to their probability of receiving pantoprazole. After propensity adjusted, multivariable logistic regression, pantoprazole treatment was found to be an independent risk factor for nosocomial pneumonia (OR, 2.7; 95% CI, 1.1 to 6.7; p = 0.034)., Conclusion: The use of pantoprazole for SUP was associated with a higher risk of nosocomial pneumonia compared with ranitidine. This relationship warrants further study in a randomized controlled trial.

Study Objective: To determine whether combining erythromycin with ranitidine is more efficacious than erythromycin or established ranitidine-metoclopramide combination in reducing the volume and acidity of gastric aspirate., Design: Randomized, double-blind study., Setting: Operating room complex., Patients: Eighty ASA physical status I and II patients., Intervention: Patients were divided into 4 groups of 20 patients each. All patients received the study medication (in tablet form) packed in identical gelatin capsules 60 to 90 minutes before surgery in the premedication room. Patients in group PP were given two placebo tablets; group EP received erythromycin 250 mg, and placebo; group ER received erythromycin 250 mg, and ranitidine 150 mg; and group RM was given ranitidine 150 mg, and metoclopramide 10 mg., Measurements: After tracheal intubation, gastric fluid was aspirated via orogastric tube, and volume and pH of the aspirate were studied., Results: Significantly higher gastric volume occurred in group PP than groups EP, ER, or RM (P < 0.001). There were no differences in volumes among groups EP, ER, and RM. Gastric pH was significantly lower (P < 0.001) in groups PP and EP than in groups ER and RM., Conclusion: Erythromycin and ranitidine combination is more efficacious than erythromycin alone in reducing the acidity and volume of gastric fluid. No difference was found between erythromycin-ranitidine and ranitidine-metoclopramide combination.

Background: Ketorolac may attenuate the maternal stress response to tracheal intubation, while avoiding opioid-induced neonatal depression. We aimed to evaluate the haemodynamic and hormonal effects of prophylactic ketorolac on surgical stress and analgesia after caesarean delivery., Methods: After ethical approval, 90 patients scheduled for elective caesarean delivery were randomly allocated receive either ketorolac 15 mg i.v. bolus 20 min before induction, followed by an infusion of 7.5 mg/h (n=45), or saline placebo (n=45). Anaesthesia was maintained with 50% nitrous oxide in oxygen with 0.5% isoflurane. Haemodynamic variables, plasma cortisol concentrations, uterine relaxation, need for supplementary doses of oxytocin, peri-operative blood loss, haematocrit, Apgar scores at 1 and 5 min, postoperative pain scores at rest and movement, and tramadol consumption were recorded., Results: After induction, patients receiving ketorolac had a smaller increase in heart rate, systolic and mean arterial blood pressure (P<0.001) and lower plasma cortisol concentrations, (32.2+/-7.61 vs. 45+/-15.1 microg/dL, P<0.05), lower pain scores at rest and movement for the first two postoperative hours (P<0.001) and a longer time to first request for analgesia. Fewer patients in the ketorolac group received tramadol in the four hours after surgery (7 (15.6%) vs. 14 (31.1%), P=0.004). There were no differences between groups in peri-operative blood loss, vomiting or Apgar scores. There was no echocardiographic evidence of premature closure of the ductus arteriosus in the newborns., Conclusion: Prophylactic ketorolac is safe and effective in attenuating the maternal stress response to intubation and improves the quality of analgesia after caesarean delivery.

Background: Even with the most effective treatment, Helicobacter pylori eradication is difficult in some patients. Therefore, patients sometimes require acid-suppressive therapy without H. pylori eradication. It has been reported that ranitidine inhibits neutrophil activation, whereas famotidine does not. However, few studies have been published concerning the activation of neutrophils before and after treatment using clinical doses of histamine-2 receptor antagonists in patients with H. pylori infection., Aim: To examine the effects of neutrophil activation after treatment with three different histamine-2 receptor antagonists., Patients: This prospective, open-label, randomised, parallel-group study was conducted. Thirty patients with H. pylori infection were enrolled. These subjects were randomly assigned to receive one of the following treatments: (a) 150 mg ranitidine, (b) 20mg famotidine, or (c) 10 mg lafutidine b.d., for 4 weeks. Before and after histamine-2 receptor antagonist treatment, histological findings, myeloperoxidase activity, and interleukin-8 in the gastric mucosa were evaluated., Results: On the basis of the histological findings between before and after histamine-2 receptor antagonist treatment, no significant differences were found in any groups. Similarly, there were no significant differences in myeloperoxidase activity or interleukin-8 levels., Conclusion: In patients with H. pylori, when used at clinical doses, any histamine-2 receptor antagonists can be used without concerning about inhibition of neutrophil activation.

Aim: Due of paucity of studies on stress ulcer prophylaxis in intracerebral hemorrhage (ICH), we have evaluated the usefulness of ranitidine and sucralfate in preventing gastric hemorrhage (GH) in patients with ICH., Subjects and Methods: In a hospital-based randomized placebo-controlled study, patients with CT-proven ICH within 7 days of ictus were randomized into ranitidine 50 mg i.v. eight hourly, sucralfate 1 g six hourly and placebo groups. Patients were conservatively managed. Primary endpoint was occurrence of GH within 15 days of ictus and secondary endpoint 1-month mortality., Results: The mean age of the patients was 57.2 (range 25-90) years and 40 were females. There were 45 patients in ranitidine, 49 in sucralfate and 47 in placebo group. Demographic, clinical and radiological features were not significantly different in 3 groups. GH occurred in 11 (23.4%) patients in placebo, 5 (11.1%) in ranitidine and 7 (14.3%) in sucralfate group, which was not significant. Only one female had GH. There were 13 (27.7%) deaths in placebo, 5 (11.1%) in ranitidine and 12 (24.5%) in sucralfate group. Pneumonia occurred in placebo group in 5 (10.6%), ranitidine in 2 (4.4%) and sucralfate in 5 (10.2%) patients, which was not significantly different., Conclusion: Ranitidine and sucralfate do not seem to significantly prevent GH or reduce 1-month mortality.

Study Objective: To describe the frequency and timing of intravenous patient-controlled analgesia (IV-PCA) or neuraxial morphine-induced postoperative respiratory depression., Design: Audit of data captured by routine quality assurance of the acute pain protocols that were implemented by nurses performing routine postoperative care., Setting: The surgical wards of a university-affiliated, 700-bed, tertiary hospital., Patients and Interventions: In real time, the data of all patients enrolled into our Acute Pain Service (APS) were entered and stored in the APS database. Thereafter, patients who had received IV morphine via a PCA device or neuraxial morphine between January 1999 and December 2002 were isolated. From this subset, all patients in whom a respiratory rate (RR) less than 10 breaths per minute was recorded were retrieved., Measurements and Main Results: From a total of 4500 patients, IV or neuraxial morphine was administered to 1524 patients. Eighteen (1.2%) cases of an RR less than 10 breaths per minute were recorded (13 patients, 4 patients, and 1 patient in the IV-PCA, daily epidural morphine, and single-dose intrathecal morphine groups, respectively). A direct correlation between intraoperative fentanyl administration and postoperative respiratory depression was demonstrated between the IV-PCA (P = 0.03) and epidural groups (P = 0.05). The time from IV-PCA initiation or last neuraxial morphine administration until the diagnosis of respiratory depression ranged between 2 hours and 31.26 hours and 2 hours and 12.15 hours, respectively. Ten (55.6%) patients received naloxone., Conclusion: Morphine-induced respiratory depression may occur at any time during the APS admission. However, the optimal frequency of intermittent RR monitoring is unknown. Furthermore, because multiple variables (age, sex, prior opioid administration, site of operation) may affect morphine-induced respiratory depression, further investigation must be performed to determine the ideal monitoring protocol.

Documentation concerning the pathogenesis of gastric hemorrhagic ulcer in Salmonella typhimurium (Salmonella typhi)-infective disease is lacking. This research first proposed that alterations of mast cell histamine release, gastric acid back-diffusion and mucosal microvascular permeability are important in modulating gastric ulcer and hemorrhage in Salmonella typhi-infected rats. Additionally, effects of several histamine-related drugs on this ulcer model were evaluated. Male Wistar rats were deprived food for 36 h. Live cultures of Salmonella typhi (OU 5045, 1 x 10(10) CFU in 1.0 mL of sterilized phosphate buffer saline) were challenged, intrajejunally to rats just before withdrawal of food. Control rats received the same volume of sterilized vehicle only. Rat stomachs were irrigated for 3 h with either normal saline or simulated gastric juice. Gastric acid back-diffusion, mucosal histamine concentration, microvascular permeability as well as luminal hemoglobin content and ulcer areas were determined. Severe gastric hemorrhage and mucosal ulcerations, particularly in acidic stomachs, were observed in Salmonella typhi-infected rats. A positive correlation of histamine to gastric hemorrhage and ulcer was found in those rats with Salmonella typhi-infection. This hemorrhagic ulcer in Salmonella typhi-infected rats was effectively ameliorated by intraperitoneal ketotifen, diphenhydramine and ranitidine but was worsen by exogenous histamine or diamine oxidase. In conclusion, enhancement of acid back-diffusion, mast cell histamine release and microvascular permeability is important in modulating gastric hemorrhage and ulcer in Salmonella typhi-infected rats.

Purpose: Previous work demonstrates that oleanolic acid (OA), a triterpene widely distributed in plants, shows gastroprotective effect in the ethanol, aspirin and pilorous ligature-induced gastric ulcer in rats as well as in the ethanol/hydrochloric acid-induced ulcer in mice. The aim of this work was to assess the healing effect of OA in the acetic acid-induced chronic gastric ulcer model in rats., Methods: Chronic gastric lesions were induced in male Sprague-Dawley rats with acetic acid. OA was administered orally during 14 days at 25, 50 and 100 mg/kg per day. Ranitidine (50 mg/kg) and the vehicle were used as controls. The ulcer area (mm2) and the curative ratio (%) were determined. Histological preparations were carried out for comparative purposes., Results: The effect of OA was significantly different as compared to the control reducing the lesion area (in mm2) from 39+/-7 in controls to 17.8+/-1.9 and 9.4+/-1.1 at the doses of 50 and 100 mg/kg, respectively. The curative ratio was 54.5 and 76% for the compound at 50 and 100 mg/kg, while ranitidine at 50 mg/kg reduced the lesion area to 6.9+/-0.8 with a curative ratio of 84%. Mucosal thickness increased from 342 microm in controls to 540 microm in oleanolic acid- (100 mg/kg) and 945 microm in ranitidine-treated animals. Histological examination of the stomach showed regeneration of the lesions., Conclusions: OA improves healing of chronic gastric lesions in rats. The low toxicity and widespread occurrence of OA in plants suggest a potential for the development of the triterpene or their derivatives as a new antiulcer drug.

Background and Aim: This prospective cohort observational study, set in a district hospital, presents our experience (1976-1993) of duodenal ulcer refractory to histamine H2 receptor antagonists (defined as not healed after 3 months' treatment) and comments on onset, outcome and spontaneous decline., Methods: Patients were treated mainly with cimetidine, the dose being titrated (up to 3.2 g daily) according to response, and followed by serial check endoscopy and clinical assessment., Results: A total of 782 of the 4032 duodenal ulcer patients seen (19%) were refractory; the incidence declined over time: 1976-1978: 124/379 (33%); 1979-1983: 390/1240 (31%); 1984-1988: 190/1295 (15%); 1989-1993: 78/1118 (7%). A total of 344 were refractory for the first time on their first healing course and 174 on their second. Healing was achieved in two-thirds after a mean of 7 months' treatment with cimetidine 1 g; treatment for 12-18 months with higher doses was needed in the remainder. Relapse occurred in up to three-quarters of patients despite maintenance cimetidine up to 3 g daily. Eventually 47 patients were operated upon but good results (i.e., no ulcer, no symptoms) were achieved in only 11., Conclusion: Refractoriness was common until recently. Its incidence has declined dramatically, the fall preceding the newer more powerful treatment with proton pump inhibitors and with Helicobacter pylori eradication. We suggest this phenomenon is a modern example of a spontaneous change in the natural history of the disease.

Since the incidence of peptic ulcer and gastroesophageal reflux (GER) is more common in patients with chronic obstructive pulmonary disease (COPD) than normal population, H(2) receptor blockers are given more extensively to COPD patients. This study evaluated the effects of Ranitidine on pulmonary function tests (PFT) of the patients having COPD and peptic ulcer or GER, and of healthy volunteers. Fifty milligrams of Ranitidine was given intravenously to 30 COPD patients and 25 healthy volunteers. PFT were done before and 15, 30, 60, 120min after Ranitidine injection. Although mean forced vital capacity (FVC), forced expiratory volume in 1s (FEV(1)) and forced midexpiratory flow rate (FEF(25-75%)) of COPD patients were found to be decreased 60 and 120min after Ranitidine injection, the decrements were statistically insignificant. The decrements in PFT of healthy volunteers were also not statistically significant.H(2) receptor blockers can be used safely for treatment of gastrointestinal disorders in COPD patients who have mild or moderate obstruction. Minimal decreases in FEV(1) and FVC due to treatment by H(2) receptor blockers may clinically worsen COPD patients who have severe obstruction.

Background and Aim: We present a survey on the incidence, demography and natural history (re-dilatation rates) of patients with oesophageal acid-peptic stricture seen between 1977 and 1995., Patients and Methods: Prospective, cohort observational study. Stricture severity was graded mild, moderate or severe (needing forcible dilatation with bougies). Most were treated with histamine H2 receptor antagonists or proton pump inhibitors, and were followed up by serial check endoscopy., Results: A total of 156 of 7429 (2%) reflux patients had stricture: mild, n=56; moderate, n=25; severe, n=75. The prevalence of reflux disease is rising, paralleled by an increase in the number of patients with stricture; hence the incidence of stricture is unchanged: 1977-1982, 1.8% (18/986); 1983-1989, 2.4% (61/2595); 1990-1995, 2% (77/3848). Demography: mean age 68 years; mean length of reflux history 6.4 years; 15% on non-steroidal anti-inflammatory drugs/aspirin; 18% with Barrett's metaplasia. Mean follow-up: 5.6 years., Outcome: of the 75 with severe stricture, 36 (48%) needed forcible dilatation only once, and 39 more often (13 twice, nine three times), most within 2 years. Only six of these patients need > or = 6 re-dilatations., Conclusion: The incidence of stricture is low and remains unchanged, despite the increased prevalence of reflux disease. Most patients have a good prognosis, only half needing further forcible dilatation, mainly within the first 2 years.

The Bristol Helicobacter Project is an ongoing, pragmatic, double-blind placebo-controlled trial of the effect of Helicobacter pylori eradication on symptoms of dyspepsia, health utilization and costs, and quality of life in the adult population. Commencing in 1996, 27,536 individuals ages 20-59 years who were registered with seven primary care centers in Bristol and the surrounding areas in southwest England were invited to undergo a 13C urea breath test. There was no selection on the basis of symptoms and 23.5% had dyspepsia on entry to the study. A total of 10,537 people were tested (38.3% of those invited), 1636 tested positive (15.5% of those tested), and 1558 (95.2% of those who tested positive) were randomized to H. pylori eradication therapy or placebo. The rate of participation in the screening phase increased with age (odds ratio [OR]: 1.42 per decade, 95% CI: 1.31 to 1.54) and female gender (OR: 1.35, 95% CI: 1.27 to 1.43) but decreased with lower socioeconomic status (OR: 0.70, 95% CI: 0.56 to 0.86 comparing lowest with highest category). H. pylori prevalence increased with age (OR: 1.69 per decade, 95% CI: 1.51 to 1.89) and lower socioeconomic status (OR: 1.33, 95% CI: 1.05 to 1.69) but was lower in women (OR: 0.87, 95% CI: 0.76 to 1.00). Population-based trials of H. pylori eradication are feasible but necessitate screening large numbers of people to identify those who are infected and who may benefit from eradication. In the Bristol Helicobacter Project the rate of participation varied inversely with both social deprivation and the prevalence of the infection.

The management of Helicobacter pylori infection is still surrounded by controversy and uncertainties. Indications and correct application of current regimens for Helicobacter pylori infection are still considered a matter of debate. Regarding indications, only peptic ulcer and mucosa associated lymphoid tissue lymphoma are considered clear indications for treatment. In other conditions, such as atrophic gastritis, post gastric cancer resection, first-degree relatives of gastric cancer patients, dyspeptic patients, patients with gastro-oesophageal reflux disease and non-steroidal anti-inflammatory drug users, the value of Helicobacter pylori eradication is still controversial. The regimens for first-line and second-line treatment of Helicobacter pylori infection have been recommended by the Maastricht 2 Consensus Report. Although all the treatments are considered to be effective, physicians still do not agree on what first-line regimen should be used. Furthermore, a consensus on the duration of the antibiotic treatment is still lacking, although Maastricht guidelines for treatment of Helicobacter pylori infection recommend a one-week therapy. Also regimens, as a third-line treatment, and methods to improve compliance and clinical outcome are still a matter of debate. All these points will be considered in the present review

The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.

A recently published meta-analysis has re-awakened the controversy regarding the risk and benefits of using acid-suppressant drugs to prevent stress ulceration in intensive care patients., (Copyright 2001 Harcourt Publishers Ltd.)

Gastroesophageal reflux (GER) is often associated with respiratory disorders. We report an unusual case of GER presented with haemoptysis. On fibreoptic bronchoscopy (FFB) a focal erythematous lesion of the mucosa of the main carina was found. Repeated FFB and biopsy excluded in situ neoplasm. Pharmacological treatment of GER with sisapride and ranitidine resulted in complete remission of the bronchial lesions. To the best of our knowledge haemoptysis with bronchoscopic lesions due to the gastroesophageal reflux has not been described previously.

Objective: Identify and critically review the peer-reviewed, English-language studies of the effects of medical antireflux therapy in asthmatics with gastroesophageal reflux (GER)., Design: Using the 1966 to 1996 MEDLINE database, asthma was combined with GER to identify all studies of the effects of medical antireflux therapy on asthma control. The articles' bibliographies were also reviewed. Studies were graded according to Sackett's criteria and grouped by levels of evidence., Results: A total of 242 citations were found; 171 were published in English. Twelve studies of the effects of medical antireflux therapy on asthma control, with a total of 326 treated patients, were identified. Eight studies were placebo-controlled, three were open studies, and one used an untreated control. Eight studies treated 20 or fewer patients. Reflux symptoms either did not improve or the effects of antireflux therapy on them were not reported in four studies. The combined data from the controlled medical antireflux studies showed that: (1) asthma symptoms improved in 69% of the subjects; (2) asthma medication use was reduced in 62% of the subjects; (3) evening peak expiratory flow (PEF), but not PEF at other times, improved in 26% of the subjects; and (4) spirometry did not improve in any of the placebo-controlled antireflux studies., Conclusions: Analysis of the combined data suggests that medical antireflux therapy improves asthma symptoms, may reduce asthma medication use, but has minimal or no effect on lung function.

We conducted a two-part controlled study to evaluate the efficacy of preoperative oral pirenzepine (muscarinic receptor antagonist known to inhibit gastric secretion), ranitidine, and the combination pirenzepine-ranitidine in controlling gastric fluid pH and volume in 210 ASA I children, aged 2-14 yr, undergoing elective surgery. In the first part of the study (n = 90), the proportion of children considered at risk for aspiration pneumonitis was reduced with pirenzepine 25 mg (P < 0.05) but not with 12.5 mg. In the second part of the study, the other 120 children were allocated randomly to one of four groups: pirenzepine 25 mg with placebo; ranitidine 75 mg with placebo; pirenzepine 25 mg with ranitidine 75 mg; and placebo and placebo. These medications were administered 1 h before anaesthesia. After tracheal intubation, volume and pH of the gastric fluid aspiration via a multiorifice orogastric tube were measured. Pirenzepine 25 mg decreased gastric fluid volume (P < 0.05) but failed to increase gastric pH. Ranitidine 75 mg increased gastric pH (P < 0.05) but failed to decrease fluid volume. The pirenzepine-ranitidine combination reduced gastric fluid acidity and volume (P < 0.05).

Unlabelled: Cardiotoxicity of cisapride may increase when this drug is associated with ranitidine., Case Report: A 37-day old term infant, treated with cisapride (1.2 mg/kg/d) and ranitidine for regurgitations, was hospitalized for malaise. A prolonged QT interval (with isolate ventricular extrasystoles), noted at admission, disappeared rapidly after cisapride withdrawal. Linkage to cisapride was probable, promoted by high dosage and cisapride metabolism inhibition by ranitidine, but its plasma concentration was not measured., Conclusion: This case report stresses the problem of cisapride dosage in infants and the question of an interaction between cisapride and ranitidine.

Purpose: To estimate the incidence of hypersensitivity reactions using a short-course intravenous prophylactic regimen in patients receiving outpatient therapy with paclitaxel., Patients and Methods: Patients were identified from a retrospective search of a computerized pharmacy database covering a two-year period from January 1994 through December 1995. Eligible outpatients received paclitaxel as a one- to three-hour infusion 30 minutes after intravenous dexamethasone (10 or 20 mg), diphenhydramine (50 mg), and cimetidine (300 mg) or ranitidine (50 mg). Charts from all patients were then manually reviewed to verify drug administration and to record any evidence of hypersensitivity reactions during the first two cycles of therapy., Results: A total of 283 outpatients were identified from the pharmacy database and all charts reviewed. All patients received intravenous dexamethasone (5 to 20 mg) 30 minutes prior to paclitaxel without prior oral dexamethasone. Hypersensitivity reactions were documented in 13 patients (4.6%) during the first or second cycle with a 95% confidence interval (CI) of 2.2% to 7.0%. Reactions resolved rapidly without sequelae and did not require hospitalization. Only two reactions (0.7%) were graded as serious with a 95% CI of 0.2% to 1.2%, based on the use of bronchodilators and presence of angioedema. Therapy was continued with modification in 10 patients without recurrent hypersensitivity reaction. Therapy was discontinued in two patients without rechallenge and discontinued in one patient after rechallenge with a recurrent hypersensitivity reaction., Conclusion: A short-course single-dose regimen of intravenous dexamethasone, diphenhydramine, and cimetidine (or ranitidine) offers a safe and convenient alternative for prevention of hypersensitivity reactions associated with outpatient paclitaxel administration.

We have compared gastric aspirate pH and volume at induction of anaesthesia in 222 patients who had received either omeprazole or ranitidine before elective operations. Omeprazole was given orally either as 40 mg on the evening before and 40 mg on the morning of surgery or as 80 mg on the morning of surgery. Ranitidine 150 mg was given orally on the evening before surgery and 2 h before anaesthesia. Treatment success was defined as aspirate pH > or = 2.5 and volume < 25 ml at induction of anaesthesia. Treatment was successful in 84% (95% confidence interval (CI) 73-91%) of patients in the omeprazole 40 + 40 mg group, 84% (95% CI 73-91%) in the ranitidine group and 73% (95% CI 61-83%) in the omeprazole 80 mg group. There were no statistically significant differences between the groups. Twelve patients in the omeprazole 80 mg group had gastric pH < 2.5 and four had volume > 25 ml. Only three patients had a gastric pH < 2.5 in the omeprazole 40 + 40 mg group and none had volume > 25 ml, which compared well with the ranitidine group. Omeprazole, given as 40 mg in the evening and 40 mg on the morning of operation, has a potential role for use in patients at risk for aspiration during general anaesthesia.

The recommended strategy for management of dyspepsia is empirical treatment with an H2-blocking drug, followed by endoscopy if the symptoms do not respond or recur. We compared two strategies for the management of dyspepsia--treatment based on the results of prompt endoscopy (group 1) and empirical H2-blocker treatment with diagnostic endoscopy only in cases of therapeutic failure or symptomatic relapse within 1 year (group 2). Eligible patients had symptoms severe enough to justify empirical H2-blocker therapy. Symptoms, drug consumption, and sick-leave days were assessed through monthly diaries. Patients with non-organic dyspepsia diagnosed by endoscopy did not receive ulcer drugs. Of 414 patients randomised, 373 completed 1-year follow-up. Organic disease was found at endoscopy in 68 (33%) of 208 group-1 patients (ulcer in 45). Endoscopy was done in 136 (66%) of 206 group-2 patients. Case selection for endoscopy was not improved by the empirical treatment strategy, since the diagnostic profile was the same as in group 1 and 40% of the expected ulcer cases remained undiagnosed. After 1 year there were no differences in symptoms or quality of life measures. The empirical treatment strategy in dyspepsia was associated with higher costs, due mainly to a higher number of sick-leave days and cost of ulcer drug use. Prompt endoscopy is a cost-effective strategy in dyspeptic patients with symptoms severe enough to justify the current practice of empirical H2-blocker treatment.

In an effort to examine the safety and pharmacology of the intraperitoneal (i.p.) delivery of paclitaxel, 25 patients (24 with ovarian cancer) were treated in a phase I dose escalation trial. The drug was administered in normal saline every 3 to 4 weeks, starting at a dose of 25 mg/m2. The dose-limiting toxicity at doses at or above 175 mg/m2 was abdominal pain. A 3-log pharmacokinetic advantage for peritoneal cavity exposure to paclitaxel, compared with the systemic compartment, was observed. High levels of drug persisted within the cavity for longer than 48 hours following a single treatment. In addition, significant paclitaxel concentrations were found in the systemic compartment after i.p. treatment, despite the pharmacokinetic advantage demonstrated for cavity exposure. Several patients exhibited clinical and laboratory evidence of an antitumor response. On the basis of these data, further exploration of a potential role for i.p. paclitaxel in the management of ovarian cancer appears justified.

Study Objective: To evaluate the effects of preanesthetic administration of intramuscular (IM) ranitidine on pH and volume of gastric contents in children., Design: Three randomized treatment groups., Setting: Central operating rooms at a university hospital., Patients: Forty children age 1 to 10 years undergoing a variety of elective surgical procedures requiring general anesthesia with endotracheal intubation., Interventions: IM ranitidine 1 mg/kg (n = 15) or 2 mg/kg (n = 15) was administered 2 hours prior to induction of anesthesia. Ten patients without ranitidine served as the control group. An orogastric tube was inserted into each patient., Measurements and Main Results: Gastric fluid pH and volume were measured every hour in the three groups. Plasma ranitidine concentrations were measured in ten patients of the ranitidine-treated groups. The mean volume of gastric fluid at induction of anesthesia was significantly lower in the ranitidine-treated patients (2.4 ml for ranitidine 1 mg/kg, 3.2 ml for ranitidine 2 mg/kg) than in the controls (8.6 ml; p less than 0.05). The mean pH values at induction of anesthesia were significantly higher in the ranitidine-treated patients (4.6 for 1 mg/kg, 6.7 for 2 mg/kg) than in the controls (2.1; p less than 0.05). Dose-dependent plasma ranitidine concentrations were obtained., Conclusions: Preanesthetic IM ranitidine 1 to 2 mg/kg resulted in a higher pH and lower volume of gastric fluid at the time of induction and in a higher pH during 3 hours of anesthesia. This therapy may be a useful adjunct to premedication for children who have a greater than normal risk of pulmonary aspiration during anesthesia.

Study Objective: To evaluate whether 360 ml of oral clear liquids consumed within 4 hours of elective surgery worsens gastric volume and acidity in patients given acid aspiration prophylaxis., Design: Randomized, unblinded study., Setting: Main operating room at a U.S. military hospital., Patients: Eighty-three adult inpatients scheduled to receive general anesthesia for elective surgery., Interventions: Nineteen patients (Group 1) were given 150 mg of oral ranitidine (two doses), 10 mg of metoclopramide, and 360 ml of apple juice 3 hours before the scheduled start of surgery. Thirty-four patients (Group 2) fasted before surgery but received acid aspiration prophylaxis identical to that given to Group 1. Twenty-three additional patients (Group 3) received no oral fluids or acid aspiration prophylaxis before surgery., Measurements and Main Results: The residual gastric volume (RGV) and the pH of Group 1 patients were compared with measurements obtained in the two groups of patients who fasted. RGV measurements in Group 1 (14 +/- 3 ml) were similar to those in Group 2 (11 +/- 2 ml) and were significantly less than (p less than 0.05) those in Group 3 (26 +/- 4 ml). Gastric pH was significantly higher (p less than 0.001) in Group 1 (5.16 +/- 0.69) and Group 2 (5.78 +/- 0.43) than in Group 3 (1.97 +/- 0.27)., Conclusions: Three hundred and sixty ml of apple juice consumed within 4 hours of elective surgery by patients given ranitidine and metoclopramide did not worsen gastric volume and acidity.

In a comparative trial of preventive medication for duodenal ulceration with 51 participating centres, 484 patients were recruited for a year's maintenance treatment with the recommended bedtime dose of ranitidine (150 mg; n = 243) or cimetidine (400 mg; n = 241). These outpatients had recently healed duodenal ulcers, confirmed by endoscopy before and after healing, and ulcer relapse was monitored by endoscopy every 4 months. The distribution of factors likely to influence ulcer recurrence was similar in the two treatment groups. A life-table method of analysis showed that the ulcer relapse rate was consistently and significantly lower on ranitidine that on cimetidine (8% v 21%, p = 0.0018 at 4 months; 14% v 34%, p less than 0.0001 at 8 months; and 23% v 37%, p = 0.004 at 12 months). Crude relapse rate calculations, which underestimate the probability of ulcer recurrence, also confirmed the significant superiority of ranitidine 150 mg over cimetidine 400 mg nightly in preventing ulcer recurrence throughout the year.

30 patients with rapidly relapsing duodenal ulceration were studied to assess the possible benefit of hypnotherapy in relapse prevention. After the ulcer had healed on treatment with ranitidine, the drug was continued for a further 10 weeks during which time patients received either hypnotherapy or no hypnotherapy. The two randomly selected groups were comparable in terms of age, sex, smoking habits, and alcohol consumption. Follow-up of both groups of patients was continued for 12 months after the cessation of ranitidine. After 1 year, 8 (53%) of the hypnotherapy patients and 15 (100%) of the control subjects had relapsed. The results of this study suggest that hypnotherapy may be a useful therapeutic adjunct for some patients with chronic recurrent duodenal ulceration.

The ability of H2 receptor antagonists and continuous enteral alimentation to maintain high intragastric pH in patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation was evaluated by continuously monitoring intragastric pH prior to and following sequential addition of ranitidine or continuous enteral alimentation (or both) to their therapeutic regimen. Prior to therapy, intragastric pH was less than 4.0 for 75 +/- 10 percent of the time, but never less than 1.0. Nevertheless, this moderate gastric acidity was associated with evidence of mucosal injury. Ranitidine failed to continuously maintain a high intragastric pH (pH less than 4.0 for 35 +/- 11 percent of the time; p greater than 0.2 compared to patients treated with placebo). Following administration of continuous enteral alimentation, intragastric pH fell, and ranitidine therapy only partially blocked this increase in gastric acidity induced by continuous enteral alimentation. We conclude that without treatment, patients with COPD who have acute respiratory failure may develop gastric mucosal injury despite the presence of only moderate intragastric acidity; however, ranitidine and continuous enteral alimentation are not effective in maintaining a high intragastric pH.