bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of octreotide on mouth‐to‐caecum transit time in healthy subjects and in the irritable bowel syndrome
Authors: O'DONNELL L. J. D. , WATSON A. J. M. , CAMERON D. , FARTHING M. J. G.
Published: July 2010

The effect of a single subcutaneous injection of octreotide (50 μg) on mouth‐to‐caecum transit time was determined in patients with the irritable bowel syndrome who complained of bowel frequency, and in healthy volunteers. The assessment of mouth‐to‐caecum transit time was performed by monitoring breath hydrogen concentration and noting a sustained 10 p.p.m. rise after ingestion of lactulose 40 ml. Measurements were performed fasting, and on a separate day, after a standard breakfast which included 40 ml lactulose. The studies were performed double‐blind in a pre‐determined random order. Octreotide prolonged mouth‐to‐caecum transit time in irritable bowel syndrome patients and healthy subjects by factors of 2.4 and 2.6 after lactulose when fasting, respectively, and by factors of 2.8 and 2.6 after the breakfast which contained lactulose. The upper gastrointestinal transit rate was similar in irritable bowel syndrome patients and healthy controls.
The interaction between Helicobacter pylori culture filtrate and indomethacin: effects on the integrity of human gastric antral mucosa and its prostaglandin E2 production in vitro
Authors: TAHA A. S. , KELLY R. W. , GEMMELL C. G. , LEE F. D. , RUSSELL R. I.
Published: July 2010

Histopathological methods and radioimmunoassay were used to assess the microstructure and prostaglandin E2 production by paired specimens of human gastric antral mucosa; the specimens were studied after 48 h of incubation in base‐line tissue culture medium, Helicobacter pylori culture filtrate, H. pylori culture control fluid, indomethacin, and H. pylori culture filtrate plus indomethacin. When applied alone, the filtrate did not affect the structure of the mucosal tissue or its prostaglandin E2 synthesis. In the overall group (n = 21), specimens incubated with the mixture of H. pylori filtrate and indomethacin had a median histological grade of 1 and prostaglandin E2 of 29 pg/mg tissue, compared to 2 pg/mg (P= 0.04) and 60 pg/mg (P= 0.0007) respectively, in specimens incubated with indomethacin alone.

These results indicate that an interaction may exist between
Maintenance therapy of duodenal ulcer with H2‐receptor antagonists—a meta‐analysis
Authors: PALMER R. H. , FRANK W. O. , KARLSTADT R.
Published: July 2010

A theoretical basis for similar recurrence rates among H2‐receptor antagonists exists based on recent concepts of ulcer recurrence, ulcer healing and suppression of nocturnal gastric acidity. In order to compare H2‐receptor antagonists in the maintenance therapy of duodenal ulcer, a meta‐analysis was carried out using 29 studies in the literature that met strict criteria. When the results of the placebo‐controlled studies were expressed as odds ratios, a technique used to minimize differences in protocol design and patient populations among studies, cimetidine, ranitidine, famotidine and nizatidine were all found to be superior to placebo to approximately the same extent. Odds ratios (and 95% confidence limits) for the recurrences in the pooled studies were cimetidine 0.22 (0.18–0.28), ranitidine 0.23 (0.18–0.30), famotidine 0.28–0.31 and nizatidine 0.36. These reflected similar 1‐year recurrence rates of 24.9% (n= 530) for 400 mg cimetidine nocte, 22.4 (n= 508) for 150 mg ranitidine nocte, 28.0% (n= 371) for 20 mg or 40 mg famotidine nocte, and 21.8% (n= 261) for 150 mg nizatidine nocte. In studies to compare cimetidine and ranitidine directly, the odds ratio (and 95% confidence limits) was 0.64 (0.48–0.86). However, for two studies done by a single protocol, the odds ratio of 0.51 (0.35–0.75) tended todiffer from the odds ratio of 0.85 (0.54‐1.33) for six other studies (P = 0.09). These reflected recurrence rates for cimetidine and ranitidine of 28.3% and 16.8% (two studies) and 23.3% and 20.6% (six studies) respectively.
Effect of intra‐colonic nicardipine on colonic motility in irritable bowel syndrome
Authors: MAXTON D. G. , WHORWELL P. J.
Published: July 2010

Intravenous nicardipine has previously been shown to abolish the effect of a 1000‐calorie meal on colonic motility. The purpose of this study was to use the same experimental design to assess the effect of nicardipine instilled directly into the colon. Each patient was studied three times when receiving either placebo, 15 mg or 30 mg nicardipine infused over 2 h. Blood concentrations of nicardipine remained very low, but neither dose of the drug affected either basal or post‐prandial colonic motility. Topical nicardipine does not appear to have therapeutic potential and its activity is probably dependent on systemic absorption.
Antioxidant therapy for recurrent pancreatitis: placebo‐controlled trial
Authors: UDEN S. , BILTON D. , NATHAN L. , HUNT L. P. , MAIN C. , BRAGANZA J. M.
Published: July 2010

Oxidant stress has been proposed as the initiating pathogenetic mechanism in pancreatitis, hence micronutrient antioxidant therapy has been assessed in patients with recurrent attacks and/or constant pancreatic pain. In a 20‐week double‐blind double‐dummy crossover trial active treatment was given as two types of tablets providing daily doses of 600 μg organic selenium, 9000 IU β carotene, 0.54 g vitamin C, 270 IU vitamin E and 2 g methionine. Of 28 patients enrolled, 20 adhered to the full protocol (idiopathic chronic 8, alcoholic chronic 7, idiopathic acute 5). Six patients had an attack whilst on placebo but none whilst on active treatment (P= 0.032). Analysis of visual analogue scoresheets to compare background pain in the 10‐week period before entry and during each phase of the trial, using a 10‐cm scale for each of 11 best descriptors, endorsed the beneficial effect of active treatment (placebo v baseline, P= 0.073; active v baseline, P < 0.001; active v placebo, P= 0.049). The same trend emerged from analysis of pain‐score diaries by conventional and time series methods. Micronutrient antioxidant therapy thus offers a new approach to the treatment of recurrent (non‐gallstone) pancreatitis and/or pancreatic pain.
Duodenal ulcer healing and acid secretory responses to modified sham feeding and pentagastrin stimulation
Authors: JOHNSTON D. A. , MARKS I. N. , YOUNG G. O. , TIGLER‐WYBRANDI N. A. , BRIDGER S.
Published: July 2010

The effect of duodenal ulcer healing on the acid secretory responses to modified sham feeding and maximal pentagastrin stimulation has been studied in 17 patients treated successfully with ranitidine (n= 9) and sucralfate (n= 8). Parietal cell sensitivity was calculated as the ratio of the modified sham feeding response to the peak pentagastrin response, expressed as a percentage. Ulcer healing after sucralfate therapy resulted in significant falls in modified sham feeding stimulated acid output (P < 0.02), from 9.4 (1.8–17.0) (median + range) to 3.7 (0.2–9.4) mmol/h; in peak acid output (P < 0.05) from 42.8 (23.0–61.4) to 27.7 (7.2–51.0)mmol/h; and in the parietal cell sensitivity (P < 0.05) from 19.2 (4.4–42.6) to 14.3 (2.8–19.7)%. No significant falls in any of these parameters were noted following ulcer healing with ranitidine. Duodenal ulcer healing with sucralfate results in decreased acid secretory responses to vagal and pentagastrin stimulation.
Efficacy of diltiazem in the treatment of diffuse oesophageal spasm
Authors: DRENTH J. P. H. , BOS L. P. , ENGELS L. G. J. B.
Published: July 2010

Calcium antagonists relax smooth muscle, a possible useful concept in treatment of diffuse oesophageal spasm. Therefore the effects of oral diltiazem (60 mg t.d.s.) and placebo were compared in eight patients with diffuse oesophageal spasm in a 10‐week double‐blind crossover study. The patients recorded the severity of chest pain and/or dysphagia in daily pain diaries using visual analogue scales. Chest pain index and dysphagia index were calculated by multiplying frequency with daily intensity of each individual symptom. When compared to placebo, diltiazem did not significantly change the overall dysphagia index and chest pain index. An individual sizeable reduction of dysphagia was attained on diltiazem in four out of six patients and in six out of eight patients suffering from chestpain. Side effects were not seen during diltiazem therapy. Diltiazem, in our study, did not yield in a significant improvement of symptoms in diffuse oesophageal spasm. Diltiazem, however, can offer relief in selected individual patients suffering from diffuse oesophageal spasm.
Short report: sedation for upper gastrointestinal endoscopy—diazepam versus midazolam
Authors: GILVARRY J. M. , CRAIG M. , FIELDING J. F.
Published: July 2010

Intravenously injected midazolam was associated with a greater degree of sedation, as assessed by 24‐h retrograde amnesia, than the longer acting benzodiazepine, diazepam. No differences in the frequency of pain on injection or the occurrence of venous sequelae were noted between the two preparations.
Prolonged inhibition of acid secretion causes hypergastrinaemia without altering pH inhibition of gastrin release in humans
Authors: KARNES W. E. , BERLIN R. G. , MAXWELL V. , SYTNIK BOYZENA , ROOT JANET K. , WALSH J. H.
Published: July 2010

Hypergastrinaemia induced by potent inhibitors of acid secretion is thought to occur as a result of the elimination of the inhibitory effects of intragastric acid on gastrin release. The present study was designed to determine if the mechanisms responsible for feedback inhibition of gastrin release and acid secretion by intragastric acid are preserved during four weeks of varying degrees of drug‐induced acid inhibition. Forty‐eight healthy male volunteers were randomly assigned to one of four treatments for four weeks: 10 mg omeprazole o.m., 20 mg omeprazole o.m., 40 mg omeprazole o.m. or 150 mg ranitidine b.d. Gastrin release and acid secretion in response to peptone meals maintained at pH 2.5 and pH 5.5 by intragastric titration, and 24‐hour gastrin profiles in response to standard meals were determined before treatment, at the fourth week of treatment and two weeks after discontinuing treatment. As expected, omeprazole produced dose‐related effects on acid secretion and gastrin concentrations that were largely reversed after treatment was discontinued. Gastrin release in response to pH 5.5 peptone meals remained significantly greater than gastrin release in response to pH 2.5 meals during treatment with all doses of omeprazole. The ratio of pH 5.5/pH 2.5 peptone meal‐stimulated gastrin release was approximately 1.5, and remained constant for all treatment groups throughout the study period. These data indicate that four weeks of drug induced hypochlorhydria causes an apparent increase in overall G‐cell function, but it does not interfere with normal feedback inhibition of gastrin release and acid secretion mediated by intragas tric acidity.
Comparison of three regimens in the management of acute gastroenteritis in infants
Authors: McCLEAN P. , LYNCH A. B. , DODGE J. A.
Published: July 2010

Sixty infants were randomly assigned to one of three groups on admission to hospital with a diagnosis of gastroenteritis. After rehydration, Group A received a low‐lactose, low‐fat feed (HN25) in full strength; Group B were regraded on to a conventional formula (SMA); Group C received a hydrolysed soya and collagen feed (Prejomin) in full strength. All feeds were continued for 5 days. The median duration of loose stools from starting the feed was 24 hours in Group A, compared to 119 hours and 95 hours in Groups B and C, respectively. Group A showed a mean percentage increase in weight of 2.34%, Group B showed a mean loss of 1.45%, and Group C a mean increase of 0.15%. These differences were statistically significant. Recovery from gastroenteritis is hastened by the use of a low‐lactose, low‐fat feed in the initial post‐rehydration phase of the disease.
Pharmacological profile of duodenal alkaline secretion
Authors: GARNER A. , HEYLINGS J. R. , HAMPSON S. E. , STANIER A. M.
Published: July 2010

Stimulation of mucosal alkaline secretion represents an opportunity for discovering novel drugs of potential benefit in maintenance therapy of duodenal ulcer disease. We screened over 200 agents representing the full spectrum of pharmacological categories in order to characterize stimulatory pathways and identify mechanistic leads. A variety of eicosanoids, phospho‐diesterase inhibitors and adrenoreceptor agonists together with forskolin, 6–hydroxy‐dopamine, 2–chloroadenosine, diazepam, testosterone, dipyridamole and dihydropyridazinone caused a reproducible increase in the metabolism‐dependent component of alkaline secretion in bullfrog proximal duodenum. PGE2(ED500.02 μg/ml) was the most potent agent in vitro and was also the most effective stimulant of duodenal alkalinization in vivo in an anaesthetized cat preparation. Agents without effect on spontaneous alkaline secretion by amphibian duodenum included agonists and antagonists of histamine, 5–hydroxy‐tryptamine, γ‐aminobutyric acid, dopamine, muscarinic and nicotinic receptors, inhibitors of amine uptake, monoamine oxidase and cholinesterase, plus various corticoids, diuretics, oestrogens, chemotherapeutic (anticancer) and antimicrobial agents. The major mechanism of stimulating alkaline secretion in the isolated duodenum is by increasing intracellular cyclic AMP levels. This may occur by either inhibiting metabolism of the nucleotide or by stimulating its formation.
Effects of low‐dose cimetidine on nocturnal acid secretion in healthy subjects
Authors: ACTON G. , BROOM C. , WAREHAM K. , LAROCHE J. , BURNHAM D. , FRIEDMAN C.
Published: July 2010

The effects of 100 mg and 200 mg bedtime doses of cimetidine on nocturnal gastric acid secretion were examined in nine healthy subjects in a double blind, placebo controlled, randomised three way crossover study. Treatment was given at 23.00 hours and the gastric contents continually aspirated from midnight until 07.00 hours the following morning. Hourly aliquots were analysed for pH and acid output. Relative to placebo the 100 mg and 200 mg doses of cimetidine respectively increased mean pH by 2.22 and 2.63 units/h (P < 0.001) with mean acid output decreasing by 0.95 and 0.98 mmol/h (P < 0.001). Whilst mean pH was higher and mean acid output was lower for 200 mg cimetidine compared to 100 mg cimetidine the difference was not statistically significant. Mean hourly pH was consistently above pH 3 for 100% of the time for both doses of cimetidine whereas mean pH failed to reach this value at anytime on placebo.

Low doses of cimetidine taken at bedtime effectively reduced nocturnal gastric acid secretion in healthy individuals.
Long‐term effects of elemental and exclusion diets for Crohn's disease
Authors: GIAFFER M. H. , CANN P. , HOLDSWORTH C D.
Published: July 2010

Previous studies have confirmed the therapeutic value 61 elemental diets in promoting remission in active Crohn's disease, but their long‐term benefit has not been established. Twenty‐seven patients with established Crohn's disease who attained clinical remission after four weeks of enteral feeding were followed prospectively for up to 36 months. Twenty of these were willing to be tested for specific food intolerance using a predefined dietary elimination protocol; the others continued on a normal unrestricted diet. Eighteen patients (67%) have since relapsed; 89% of the relapses occurred within the first 6 months. Of the 15 patients with colonic involvement, 12 (80%) relapsed by 6 months. In contrast only 3 of 11 with isolated small bowel disease experienced early relapse. Of the 14 patients who completed the process of dietary testing, 5 could not identify any trigger foods; the remaining 9 were maintained on exclusion diets, 3 of whom relapsed early. Of the 11 taking a normal diet, 9 relapsed. Disease duration, previous intestinal resection or prior steroid therapy did not affect the relapse rate. Eight patients (31 %) obtained a long‐term remission, mean 23 months (range 12–36 months), without any medication. Long‐lasting remissions can be obtained in about one‐third of patients with Crohn's disease following treatment with a defined formula diet. Colonic involvement is associated with a high early relapse rate.
The effects of renzapride, a novel prokinetic agent, in diabetic gastroparesis
Authors: MACKIE A. D. R. , FERRINGTON C , COWAN S. , PALMER K. R.
Published: July 2010

Gastric emptying was measured in 9 diabetic patients with autonomic neuropathy (Group 1) and 8 normal controls (Group 2) on 4 occasions after swallowing placebo, 0.5, 1.0 or 2.0 mg of the newly developed prokinetic drug renzapride given double‐blind and in random order. The liquid component of the test meal was labelled with In113mand the solid with Tc99m. Liquid emptying was uni‐exponential. Solid emptying comprised an initial lag phase, followed by a linear component. Following placebo, the mean lag phase of solid emptying was 40 ± 7 (S.E.M.) min in Group 1 and 16 ± 2 min in Group 2 (P< 0.01). In Group 1 subjects renzapride reduced the mean lag phase by 20–26 min at all doses (P< 0.01). No effect was seen in Group 2. The linear rate of solid emptying was similar in both groups (0.9 ± 0.1 and 1.0 ± 0.2%/min) and was not altered by renzapride. Mean liquidt1/2was similar in Groups 1 and 2 after placebo (30 ± 6 and 29 ± 4 min, respectively) and was decreased with increasing doses of renzapride in both groups. No adverse effects were encountered in any subjects. Renzapride may be useful in the treatment of diabetic gastroparesis.
Morphometric studies in duodenal biopsies from patients with coeliac disease: the effect of the steroid fluticasone propionate
Authors: ZAITOUN A. , RECORD C. O.
Published: July 2010

Morphometric measurements have been performed on small intestinal biopsy specimens from patients with untreated coeliac disease before and after six weeks oral treatment with a steroid of low systemic bioavailability (fluticasone propionate). Measurements were obtained by point counting and also by a computer‐aided measuring system with reference to a constant area of the muscularis mucosa.

Fluticasone propionate led to a parallel reduction in the intra‐epithelial lymphocyte count within the surface (P < 0.001) and crypt epithelium (P < 0.01). The intra‐epithelial lymphocyte count assessed by reference to constant areas of the muscularis mucosa and surface epithelium were decreased two‐fold (P < 0.01) and seven‐fold (P < 0.001) respectively. Fluticasone propionate treatment also led to significant increases in the absorptive surface epithelium as shown by an increase in the villus: crypt ratio (P < 0.01), the epithelial cell height (P < 0.01) and two‐ to three‐fold increases in the area and length of the surface epithelium (P < 0.001).

Short‐term fluticasone propionate treatment appears to exert a powerful beneficial effect upon duodenal morphology in patients with coeliac disease. Whether the alterations seen are comparable to a similar period of gluten withdrawal is not yet known.
A controlled study of 20 mg famotidine nocte vs. 150 mg ranitidine nocte for the prevention of duodenal ulcer relapse
Authors: PORRO G. BIANCHI , LAZZARONI M. , BARBARA L. , CORINALDESI R. , BLASI A. , MANGIAMELI A. , CAPURSO L. , KOCH M. , CHELI R. , BOVERO E. , FRANCHIS R. DE , GUSLANDI M. , FRANCAVILLA A. , INGROSSO M. , GASBARRINI G. , ZOLI G. , MAZZACCA G. , SABBATINI F. , NACCARATO R. , MARIO F. DI , PAOLUZI P. , AGNELLO M. , SCURO L. A. , CAVALLINI G. , SURRENTI C. , CALACRO A.
Published: July 2010

A 24‐week, double‐blind, randomized study at 13 centres compared the efficacy and safety of 20 mg famotidine nocte and 150 mg ranitidine h.s. for the prevention of duodenal ulcer recurrence. All participants had been successfully treated for an acute duodenal ulcer with 40 mg famotidine nocte. Patients were endoscoped at baseline and at 24 weeks, unless symptoms warranted earlier examination: of the 208 patients enrolled, 86 who received famotidine and 84 who received ranitidine met all protocol criteria and were considered evaluable.

Intention to treat and per protocol analyses showed non‐significant trends in favour of famotidine (P= 0.44 and 0.16, respectively). During the 24‐week observation period, 16.3% of the famotidine group and 25% of the ranitidine group had an ulcer recurrence (95% CI of percentage difference –0.22 + 0.04). At 24 weeks, relief of day and night pain was reported by 81.2% and 91.8% of the famotidine‐treated patients, respectively. The corresponding figures in the ranitidine group were 73.5% and 85.5%.

No laboratory abnormalities related to the study‐drugs were noted and only two drug related (possibly or probably) adverse experiences were reported, both in the famotidine group. The data from this study therefore, supports the conclusion that the efficacy of 20 mg famotidine nocte is comparable to that of ranitidine in preventing duodenal ulcer recurrence, with comparable tolerability for long‐term therapy.
Review article: dietary and nutritional management of Crohn's disease
Authors: RUSSELL R. I.
Published: July 2010

The value of dietary alteration and the nutritional management of Crohn's disease is assessed in this review.

Lactose restriction, low‐fat diets and low‐residue diets may be of value in specifically indicated clinical situations. A fibre‐rich, unrefined carbohydrate diet has not been shown to alter the course of the disease, and the value of ‘exclusion diets’remains to be confirmed in controlled, prospective studies.

Nutritional insufficiency of varying degrees is common in Crohn's disease and can be corrected by the efficient use of enteral diets (usually with polymeric preparations) or intravenous nutritional support. Growth retardation in adolescents with Crohn's disease can usually be improved by enteral nutrition.

Nutritional support of various kinds may be of value in the management of local complications of Crohn's disease; sub‐acute obstruction, anal, perianal and rectal lesions, fistulas and ileostomy complications, and the management of bile acid‐induced diarrhoea.

The use of nutrition as ‘primary therapy; in Crohn's disease is considered. Theoretical reasons why nutritional support and bowel rest may possibly induce remission of the disease are discussed. The evidence to date suggests that intravenous nutrition and bowel rest may not be effective in inducing a primary remission of the disease, and the possible value of elemental diets and polymeric diets in this respect are assessed. Further prospective controlled studies of elemental diets as primary therapy in Crohn's disease are required.
Suppression of castor oil‐induced diarrhoea by α2‐adrenoceptor agonists
Authors: THOLLANDER M. , HELLSTRÖM P. M. , SVENSSON T. H.
Published: July 2010

The effects of systemic administration of α2‐adrenoceptor agonists on migrating myoelectric complexes and castor oil‐induced diarrhoea of the small intestine were studied in conscious rats. Castor oil (1 mg/kg, intraduodenally) disrupted the migrating myoelectric complexes and induced irregular spiking activity with sporadic bursts of myoelectric activity. This change of motility pattern was present concomitant with diarrhoea 1–2 h after instillation of castor oil and during the whole period of diarrhoea. Pre‐treatment with clonidine (5–10 μg/kg i.v.) or oxymetazoline (5.6–11.2 μg/kg i.v.), a peripherally active α2‐agonist, inhibited the irregular spiking induced by castor oil and no diarrhoea occurred during the experimental period of 6 h. Thus, the antidiarrhoeal action of peripherally acting α2‐adrenoceptor agonists such as oxymetazoline, may be of clinical value in the treatment of diarrhoea.
A comparison of roxatidine and ranitidine for the acute treatment of duodenal ulcer
Authors: WALT R. P. , LOGAN R. F. A. , HAWKEY C. J. , DANESHMEND T. K. , LONG R. G. , COOPER B. T. , LANGMAN M. J. S. , COLLINS M. , STREET R.
Published: July 2010

Roxatidine acetate is a new histamine H2‐antagonist of about twice the potency of ranitidine on a weight‐for‐weight basis. Two hundred and thirty‐two patients participated in a double‐blind randomized trial of duodenal ulcer healing comparing 300 mg ranitidine nocte with 150 mg roxatidine nocte. Endoscopy was repeated fortnightly to 4 weeks in each of four participating centres. Usual exclusion criteria applied but NSAID users were allowed. There were no important demographic differences between treatment recipients. Three analyses were used: protocol (dropouts and violators not included), intention‐to‐treat I (dropouts considered failures), and intention‐to‐treat II (dropouts considered failures, but violators outcome included). Healing rates differed markedly (but not significantly) with each analysis. After 2 weeks of treatment ulcers had healed in 51% versus 45% using the intention to treat I analysis with roxatidine and ranitidine, respectively; by the protocol analysis the healing proportions were 60% and 55%. These differences between treatments were not significant. After 4 weeks of treatment healing rates ranged from 71% to 83% on roxatidine and between 69% and 84% on ranitidine depending on the analysis. Differential healing proportions of smokers and non‐smokers were nonsignificant (83% vs. 79%). Both drugs were well tolerated and adverse events were similar with each agent. Roxatidine should prove as effective as ranitidine for acute duodenal ulcer treatment.
Effects of ranitidine on maternal gastric juice and neonates when administered prior to caesarean section
Authors: IKENOUE T. , IITO J. , MATSUDA Y. , HOKANISHI H.
Published: July 2010

Ranitidine hydrochloride, a histamine H2‐receptor antagonist, was intravenously administered to 61 pregnant women at a dose of 50 mg as premedication for caesarean section; its effects on gastric secretion were studied in the mother and the newborn.

The volume of the maternal gastric juice collected immediately after the induction of anaesthesia averaged 14.0 ± 10.0 ml with pH 3.48 ± 1.70, and at the time of extubation, 3.6 ± 2.8 ml with pH 4.19 ± 1.79, respectively.

Forty‐four full‐term neonates whose mothers had received ranitidine were selected to investigate the effects of ranitidine. Another 45 full‐term normal newborns delivered vaginally, and 14 by caesarean section, served as controls.

No effects of ranitidine infusion in the mothers were detected in the newborn children. The gastric pH of the newborn at birth and 24 hours after birth, gastrointestinal symptoms and the general growth checked at the regular one‐month work‐up after birth did not differ in test and control groups.
Omeprazole
Authors: LANGMAN M. J. S.
Published: July 2010

Omeprazole is a potent and effective antisecretory drug. Benefits in gastric and duodenal ulceration nevertheless seem marginal because standard treatments are very effective. More obvious advantages are discernible in oesophageal reflux disease where more profound acid inhibition may be needed to obtain symptom relief. Fears of important adverse effects either through inducing ECL cell hyperplasia or outright carcinogenesis, do not seem firmly founded, nor is there convincing evidence of significant interactions with other xenobiotics. Nevertheless, continued caution seems justified.
Rebound hypersecretion after H2‐antagonist withdrawal—a comparative study with nizatidine, ranitidine and famotidine
Authors: FULLARTON G. M. , MACDONALD A. M. I. , McCOLL K. E. L.
Published: July 2010

Our previous study demonstrated rebound nocturnal acid hypersecretion after a 4‐week course of nizatidine. Nocturnal acid output was increased by 77% two days after discontinuing treatment compared with pretreatment values. To confirm this effect with other H2‐blockers we assessed daytime intragastric pH, fasting and meal‐stimulated plasma gastrin and nocturnal acid output in 9 duodenal ulcer patients in remission before, during and two days after treatment with three different drugs. Each patient received 4‐week courses of 300 mg ranitidine, 40 mg famotidine or 300 mg nizatidine, taken at 20.00 hours in randomized order with a ‘washout’period of 4 weeks between each course of drug. Median nocturnal acid output (mmol/10 h) decreased during treatment with ranitidine to 3 (range 0–17), famotidine to 4 (1–12) and nizatidine 6 (0–40) compared with the respective pre‐treatment values, 49 (20–126;P< 0.01), 52 (22–105;P< 0.01) and 32 (23–114;P< 0.01). Two days after discontinuing treatment nocturnal acid output was increased after ranitidine at 77 (28–237;P< 0.04) and after nizatidine at 64 (17–130;P< 0.05) compared with pre‐treatment values.

There was no significant change in nocturnal acid output after famotidine at 57 (27–107) compared with the pre‐treatment value. There was no change in daytime intragastric pH with any drug during or after treatment compared with the pre‐treatment values. Fasting and meal‐stimulated plasma gastrin concentrations were increased on the final treatment day with ranitidine and famotidine but had returned to pretreatment levels two days after treatment. The rebound acid hypersecretion may contribute to the high ulcer relapse rate after discontinuation of H2‐receptor antagonists.
Effect of anti‐obesity drugs promoting energy expenditure, yohimbine and ephedrine, on gastric emptying in obese patients
Authors: JONDERKO K. , KUCIO C.
Published: July 2010

The effect of ephedrine, a non‐selective adrenoreceptor agonist, and yohimbine, a selective alpha2‐adrenolytic drug, on gastric emptying of a radiolabelled solid meal was examined in groups of 8 (all women) and 15 (4 men and 11 women) obese patients, respectively. Patients were given orally, double‐blind in random order, placebo or 50 mg ephedrine in the first group, and placebo or 15 mg yohimbine in the second group, 1.5 h prior to the gastric emptying measurement performed with the use of a gamma camera. Yohimbine did not significantly affect gastric emptying—the fraction of the meal retained within the stomach at the end of the examination (that is after 90 min), F90, amounted to 71.0 ± 3.8% (placebo) and 66.8 ± 4.1% (yohimbine); the gastric emptying index, Ix, was 0.737 ± 0.106 min−1× 10−2 (placebo) and 0.885 ± 0.128 min−1× 10−2 (yohimbine). A significant delay in gastric emptying was observed after administration of ephedrine: F90 increased from 70.3 ± 5.1% after placebo to 80.9 ± 3.0% after ephedrine, P < 0.02, and Ix decreased from 0.747 ± 0.142 min−1× 10−2 to 0.461 ± 0.080 min−1× 10−2 after ephedrine, P < 0.02. We conclude that the inhibitory influence of ephedrine on gastric emptying, and thus possibly on satiety, makes it a candidate for trial as pharmacological support of a low‐energy diet treatment of obesity.
Protection from gastrointestinal side‐effects by azapropazone by its incorporation into a glucose—sodium acid citrate formulation
Authors: RAINSFORD K. D. , DIEPPE P. A. , PRITCHARD M. H. , RHODES J. , LEACH H. , RUSSELL R. I. , WALKER F. S. , UPADHYAY R. , HORT J. F.
Published: July 2010

Addition of glucose and sodium citrate to azapropazone, in proportions of 1:1:1 by weight reduced gastric mucosal damage in rats and there was a trend towards reduction in radiolabelled faecal red cell loss in human volunteers compared with that with azapropazone alone. The glucose and citrate did not affect the pharmacokinetics of azapropazone, or its therapeutic efficacy. While no difference was observed in endoscopic injury and in symptomatic gastrointestinal complaints in a multicentre comparison in rheumatic patients, a striking reduction in symptoms was observed in those patients with a history of severe gastrointestinal intolerance to non‐steroidal anti‐inflammatory drugs.
Short report: the effect of omeprazole on Helicobacter pylori and associated gastritis
Authors: DAW M. A. , DEEGAN P. , LEEN E. , O'MORÁIN C.
Published: July 2010

Twenty‐one patients with endoscopically confirmed duodenal ulceration, who had failed to heal with an H2‐antagonist, were given omeprazole 20 mg o.m. for four weeks. Four antral biopsies from each patient were taken at endoscopy before, at the end of, and four weeks after treatment. Rapid urease test, culture, histopathology and transmission electron microscopy were carried out on these biopsies to determine the presence of Helicobacter pylori and improvement of gastritis. After four weeks of treatment, duodenal ulceration was healed in 16 (79%) of the patients; H. pylori was not detected by culture in 11 (50%) of the patients, and the associated gastritis improved in 12 (54%) patients. Four weeks after cessation of treatment the organism was cultured from antral biopsies of 18 (86%) of the patients and all of these had gastritis. Omeprazole treatment healed duodenal ulceration, improved gastritis temporarily, and suppressed but did not eradicate H. pylori.
Effects on bowel motility of misoprostol administered before and after meals
Authors: RUTGEERTS P. , VANTRAPPEN G. , HIELE M. , GHOOS Y. , ONKELINX C.
Published: July 2010

Prostaglandin analogues, used in the treatment of duodenal and benign gastric ulcer and in the prevention of gastric ulceration caused by nonsteroidal anti‐inflammatory drugs, are frequently associated with gastrointestinal side effects, particularly diarrhoea and abdominal cramps. We investigated the effects of misoprostol, a prostaglandin E1 derivative, on bowel motility and faecal loss of fat, water and bile acids in relation to its postprandial vs. preprandial administration. Twelve healthy subjects participated in a double‐blind crossover study comparing three 5‐day courses of therapy with a washout period of 1‐2 weeks between courses. Following a Latin Square design, the dosing regimens were (a) 400 μ misoprostol b.d. after meals and placebo b.d. before meals; (b) 400 μ misoprostol b.d. before meals and placebo b.d. after meals; (c) placebo before and after meals. Orocaecal transit time measured by H2 breath tests following lactulose administration, was shortest during pre‐prandial dosing but was also significantly decreased during post‐prandial dosing. The overall treatment difference was highly significant (P < 0.001), and the difference between each pair of treatments was also statistically significant. Whole bowel transit time studied by means of 3H‐PEG 4000 determination in stools, was shorter for the two misoprostol regimens but statistical significance was borderline. The number of stools passed per day was similar in the three groups. During both misoprostol dosing periods, stools were less formed and their content of water, fat and bile acids was higher. There was also more urgency, flatulence, abdominal pain and nausea. It is concluded that the gastrointestinal side effects caused by misoprostol are mainly based on an increased orocaecal transit time. The effects are more important when the drug is administered before meals than after meals.
Short report: plasma aluminium concentration and 24‐hour urinary aluminium excretion before, during and after treatment with sucralfate
Authors: MISTRY P. , VARGHESE Z. , POUNDER R. E.
Published: July 2010

Ten dyspeptic patients were treated with 1 g sucralfate q.d.s. for six weeks. The plasma aluminium concentration and 24‐h urinary aluminium excretion were measured at 3‐weekly intervals before, during and after treatment with sucralfate. Compared with before treatment, there were significant rises in the median plasma aluminium concentration at 3 and 6 weeks during treatment with sucralfate (6 μ/L to 13 and 12 μ/L). The median 24‐h urinary aluminium excretion rose significantly from a pretreatment level of 20 μ to 71 and 78 μ after 3 and 6 weeks of treatment; the significant increase of urinary aluminium excretion persisted for three weeks after cessation of treatment (52 μ/24 hours), but thereafter urinary excretion was not significantly different from pretreatment. The results are consistent with significant absorption and tissue accumulation of aluminium during standard treatment with sucralfate in individuals with normal renal function.
Review article: the histamine H3‐receptor: a novel prejunctional receptor regulating gastrointestinal function
Authors: BERTACCINI G. , CORUZZI G. , POLI E.
Published: July 2010

This review examines the evidence for the existence in the gastrointestinal tract of a new subtype (H3) of histamine receptors, previously described in the central nervous system. Study of these receptors is facilitated by the availability of the highly selective agonist (R)α‐methylhistamine and the selective antagonist, thioperamide. H3‐receptors seem to exert negative control on gastric acid secretion evoked by indirect cholinergic stimuli: their localization is unclear but it seems to be outside the parietal cell. H3‐receptors also seem to be located on cholinergic and non‐adrenergic non‐cholinergic (NANC) neurones of the myenteric plexus, where they negatively control the release of neurotransmitters.
The effect of bile acids on the growth and adherence of Helicobacter pylori
Authors: MATHAI E. , ARORA A. , CAFFERKEY M. , KEANE C. T. , O'MORAIN C.
Published: July 2010

Bile reflux gastritis occurs in the absence of Helicobacter pylori (H. pylori). The aim of this study was to see if the bile acids cheno or ursodeoxycholic acid affected the growth or adherence of H. pylori in vitro. Twenty‐seven strains growth were inhibited by 0.1% chenodeoxycholic acid whereas only 11 out of the 27 were inhibited by 0.1% ursodeoxycholic acid. Growth was totally inhibited by a combination of 0.05 % chenodeoxycholic acid + 0.05 % ursodeoxycholic acid. Chenodeoxycholic acid was a more effective inhibitor of adherence in that the number inhibited and percentage inhibition were greater than with ursodeoxycholic acid. Bile salts might be useful in the treatment of H. pylori infection.
Short report: plasma somatostatin concentrations in the irritable bowel syndrome
Authors: O'DONNELL L. J. D. , DAVIDSON K. , CAMERON D. , WASS J. A. H. , FARTHING M. J. G.
Published: July 2010

The description of a patient with the irritable bowel syndrome whose symptoms were completely relieved by the administration of somatostatin raised the possibility that a deficiency of somatostatin may be involved in the pathogenesis of the disorder. We have examined this possibility by studying 11 healthy controls (35 ± 12 years; mean ± S.D. 8 female) and 10 irritable bowel syndrome patients (39 ± 14 years; 7 female) complaining of frequency of defaecation of 4 or more times a day. Plasma somatostatin concentrations were determined by specific radioimmunoassay, fasting and at 15, 30, 45, 60, 90, 120 and 180 min after a standard breakfast. Irritable bowel syndrome patients and controls had similar fasting (27.4 ± 5.1 vs. 35.2 ± 4.3 pg/ml; mean ± S.E.M. and integrated increment of post‐prandial (5105 ± 858 vs. 3885 ± 793 pg. min/L) plasma concentrations of somatostatin, as assessed by student's t‐test. These observations do not support the idea that a state of somatostatin deficiency exists in the irritable bowel syndrome.
Idiopathic gastric acid hypersecretion: treatment implications for refractory acid/peptic disorders
Authors: LEWIS J.H.
Published: July 2010

Although in most patients with duodenal ulcer disease the ulcer heals after 8 weeks of treatment with standard doses of H2 blockers or other agents, in about 10% the ulcer does not heal. These patients are considered ‘refractory’to treatment. Reasons often cited for non‐healing include poor patient compliance, cigarette smoking, and non‐steroidal anti‐inflammatory drug (NSAID) use. Gastric acid hypersecretion also appears to be an important factor in non‐healing with standard doses of antisecretory agents. We have defined idiopathic gastric acid hypersecretion as a basal acid output of > 10 mmol/h in the absence of an elevated fasting serum gastrin level (or a negative secretin test if gastrin level > 100 pg/ml) to exclude persons with Zollinger‐Ellison syndrome. Among the acid/peptic‐related disorders in which idiopathic gastric acid hypersecretion should be considered are refractory duodenal ulcer, refractory gastro‐oesophageal reflux disease (especially patients with oesophagitis), postbleeding duodenal ulcer, and certain rare disorders such as hereditary angioedema. Some children with atypical abdominal pain may also be hypersecretors of gastric acid.

Once identified, patients with refractory duodenal ulcer or gastrooesophageal reflux disease are treated with incremental doses of ranitidine titrated against the level of gastric acid secretion that remains during therapy. Ranitidine was selected to avoid the dose‐related antiandrogenic effects and potential hepatic cytochrome P450 system‐related drug interactions that may occur with cimetidine. In most cases of refractory duodenal ulcer, doubling the standard dose of ranitidine (to 300 mg b.d.) is sufficient to achieve symptomatic relief and mucosal healing. Higher doses appear to be necessary for refractory oesophagitis. To date, no side effects have been associated with high doses of ranitidine (up to 1800 mg/day) for periods of longer than 6 months. Idiopathic gastric acid hypersecretion is an important factor in explaining why not all patients respond to a ‘standard’ulcer‐healing dose of H2 blocker, and it provides a rationale for use of higher‐dose therapy as a safe and effective alternative to omeprazole or to combination drug therapy in refractory acid/peptic disease.
Pathophysiology of NSAID‐induced gastroduodenal damage: epidemiology and mechanisms of action of therapeutic agents
Authors: IVEY K. J.
Published: July 2010

All NSAIDs cause gastroduodenal mucosal damage. The mechanisms by which NSAIDs damage the mucosa are not fully understood. Peptic ulcers appear to be caused by an imbalance between acid output and mucosal resistance; therapeutic agents that act favourably on either variable will heal NSAID‐induced ulcers, particularly if the NSAID is discontinued. Inhibition of acid secretion and/or stimulation of prostaglandin secretion are also believed to have a protective effect against NSAID‐induced mucosal damage. Thus, antisecretory agents, such as the H2 blockers, and prostaglandin analogues, such as misoprostol, can provide protection against NSAID‐induced gastroduodenal damage.
Drug interactions with antisecretory agents
Authors: HANSTEN P. D.
Published: July 2010

Antisecretory agents may affect the absorption, metabolism, and renal excretion of other drugs. Inhibition of gastric acid secretion may decrease the gastrointestinal absorption of drugs such as ketoconazole that dissolve poorly in the absence of adequate acid. With anti‐secretory agents, the drug interaction mechanism most likely to result in adverse effects is the inhibition of hepatic oxidative drug metabolism, primarily a problem with cimetidine. Omeprazole also appears to inhibit the hepatic metabolism of some drugs, but available evidence indicates that it interacts with fewer drugs than cimetidine and the magnitude of the inhibition is lower. Cimetidine decreases the renal clearance of procainamide and its active metabolite, N‐acetylprocainamide, probably through interference with active renal tubular secretion. In therapeutic doses, other H2‐receptor antagonists probably have minimal effects on renal procainamide elimination.
Pharmacokinetics and absolute rectal bioavailability of hydrocortisone acetate in distal colitis
Authors: PETITJEAN O. , WENDLING J. L. , TOD M. , LOUCHAHI K. , NICOLAS P. , PERRET G. , ASTIER A.
Published: July 2010

The hydrocortisone pharmacokinetic profiles of hydrocortisone acetate foam (Proctocort) administered rectally was assessed in healthy volunteers and patients with ulcerative colitis or X‐irradiation colitis. Endogenous production of hydrocortisone was suppressed by dexamethasone. Comparison of these data with those obtained after intravenous administration enabled assessment of absolute bioavailability, which was 30.0 ± 15.1% in healthy volunteers vs. 16.4 ± 14.8% in patients (P= 0.09). Maximal concentrations of hydrocortisone were also decreased in patients, 277 ± 215 nmol/L vs. 610 ± 334 mmol/L (P= 0.03). There was a nonsignificant tendency to faster absorption of hydrocortisone in patients vs. healthy volunteers, as the times to peak concentration were, respectively, 2.5 ± 1.2 h vs. 2.8 ± 0.8 h (P= 0.64), and the mean absorption times were 1.96 ± 1.45 h vs. 2.54 ± 1.62 h (P= 0.46). Thus, rectal inflammation resulted in a lower absorption of hydrocortisone. In addition systemic plasma levels remained in the physiological range, so that only minor side effects are to be expected.
Effects of oral pantoprazole on 24‐hour intragastric acidity and plasma gastrin profiles
Authors: HANNAN A. , WEIL J. , BROOM C. , WALT R. P.
Published: July 2010

Pantoprazole selectively blocks gastric parietal cell H+,K+‐ATPase. To define a dosage regimen for clinical trials we compared the effect of pantoprazole 40 and 60 mg daily on 24‐h intragastric acidity and plasma gastrin concentrations using a double‐blind, randomized, cross‐over design. Eleven men took each of the three regimens (placebo, 40, 60 mg) for 5 days. On Day 5, 24‐h pHmetry and plasma gastrin profile were performed. A consistent decrease in intragastric acidity with each dosage regimen was shown by a rise in 24‐h median pH from 1.4 (1.2–1.8, IQR) on placebo to 2.3 (1.8–4.4, P= 0.0022) during pantoprazole 40 mg and to 3.5 (2.6–4.9, P= 0.0017) during 60 mg. Pantoprazole 40 and 60 mg maintained the intragastric pH above 3 for 33% and 58% of time, respectively, compared with 15% time with placebo. Twenty‐four‐hour integrated plasma gastrin concentration rose from 478 to 1798 and 1962 pmol.h/L, respectively. The drug was well tolerated. The decrease of acidity was dose related and should result in clinical efficacy similar to other antisecretory drugs. It is not known whether higher doses might abolish acid secretion. The optimal dose of pantoprazole is yet to be established.
Helicobacter pylori lipopolysaccharide stimulates gastric mucosal pepsinogen secretion
Authors: YOUNG G. O. , STEMMET N. , LASTOVICA A. , MERWE E. L. VAN DER , LOUW J. A. , MODLIN I. M. , MARKS I. N.
Published: July 2010

The effect of Helicobacter pylori lipopolysaccharide on guinea pig gastric mucosal pepsinogen secretion has been examined using an Ussing chamber technique. Luminal addition of H. pylori lipopolysaccharide resulted in a fifty‐fold stimulation of pepsinogen secretion compared to a twelve‐fold increase with E. coil lipopolysaccharide. Electron microscopy showed marked degranulation of zymogen granules but no evidence of chief cell disruption.
Circadian differences in pharmacological blockade of meal‐stimulated gastric acid secretion
Authors: SANDERS S. W. , MOORE J. G. , DAY G. M. , TOLMAN K. G.
Published: July 2010

The effects of identical morning (08.05 hours) and evening (20.05 hours) meals on intragastric pH were compared in 12 healthy volunteers receiving gastric antisecretory medication. Dosing included continuous intravenous infusion ranitidine (50 mg bolus followed by 12.5 mg/h) or a matching placebo which were randomly administered prior to and following 7 days of treatment with oral omeprazole (40 mg mane). Intragastric pH was monitored continuously using a tethered indwelling pH probe. Subjects were divided into groups, one of which began the pH monitoring session in the morning, the other in the evening. The median 24‐h intragastric pH was significantly increased by all active dosing regimens (P < 0.05). Combined omeprazole and ranitidine produced the highest median pH, 5.92. However, a breakthrough drop in intragastric pH occurred during the evening after all active dosing. Intragastric pH fell prior to and after consumption of the evening meal with median pH values less than 4 during all sessions. The evening meal led to significantly lower intragastric pH compared to the morning meal for omeprazole and the combined omeprazole and ranitidine dosing periods (P < 0.05). There was no difference between morning and evening pH during the placebo or ranitidine periods. Ranitidine and omeprazole, either alone or in combination, were unable to prevent the mealstimulated decline in intragastric pH during the evening time period.