bluuebunny/crossref_metadata_2025 huggingface dataset:
β‐Galactosidase from Aspergillus niger in adult lactose malabsorption: a double‐blind crossover study
Authors: CORAZZA G. R. , BENATI G. , SORGE M. , STROCCHI A. , CALZA G. , GASBARRINI G.
Published: July 2010

An assessment was made of the efficacy of a β‐galactosidase, obtained from Aspergillus niger and added to intact milk, in decreasing lactose malabsorption and intolerance. Sixteen adult patients with malabsorption and intolerance to this sugar were studied in a double‐blind crossover study vs. placebo. A 5‐hour hydrogen breath test was used to assess malabsorption of lactose contained in 400 ml milk. When compared with placebo, the addition of exogenous lactase to intact milk caused a statistically significant reduction in the maximum breath H2 concentration (P < 0.01) and in the cumulative H2 excretion (P < 0.005). In the same way, the cumulative index for gastrointestinal intolerance was significantly lower (P < 0.005) after the ingestion of lactase‐added milk. This study demonstrates that enzyme replacement therapy, with β‐galactosidases obtained from Aspergillus niger, is effective in decreasing lactose malabsorption and its consequent intolerance in adult subjects with lactase deficiency.
Review article: metabolic consequences of long‐term inhibition of acid secretion by omeprazole
Authors: KOOP H.
Published: July 2010

Metabolic sequelae of profound and long‐lasting inhibition of gastric acid secretion by omeprazole have largely been neglected. Data from long‐term studies suggest that vitamin B12 stores decrease slightly over several years, although this was not clinically relevant within the first 4 years of therapy. Additionally, it cannot be completely ruled out that patients with an increased iron demand may develop iron deficiency, but data available at present do not provide any evidence that iron malabsorption is to be expected under normal conditions. Protein homeostasis and calcium metabolism seem to be unaffected by long‐term omeprazole therapy. Based upon present experience, serum cobalamin concentration should be monitored in patients undergoing omeprazole therapy for several years.
Effect of potassium chloride on gastric acid secretion and gastrin release in humans
Authors: FELDMAN M. , GOLDSCHMIEDT M.
Published: July 2010

The effect of potassium chloride on gastric acid secretion and gastrin release was studied in 6 healthy human beings. On 3 separate days and in random order, subjects received an intragastric infusion of 0.5 L of a glucose‐saline solution to which had been added 40 mmol KCl, 40 mmol NaCl, or no additional salts. All test solutions stimulated acid secretion and gastrin release to a similar degree. While potassium ions play a critical role in acid secretion by parietal cells (via the H+, K+‐ATPase), KCl administered into the gastric lumen at a concentration of 80 mmol/L has no effect on acid secretion in man.
Co‐administration of misoprostol or ranitidine with indomethacin: effects on pharmacokinetics, abdominal symptoms and bowel habit
Authors: KENDALL M. J. , GIBSON R. , WALT R. P.
Published: July 2010

This three‐way randomized crossover study in 18 healthy male volunteers compared the pharmacokinetics of 50 mg indomethacin b.d. during concomitant twice daily dosing with 400 μg misoprostol, 150 mg ranitidine or placebo. Plasma indomethacin concentrations were determined by HPLC assay of samples collected over 12 h after the first dose, and over 14 h after the last dose on Day 8 of each dosing period. A daily diary of bowel habits, and the occurrence and severity of abdominal symptoms, was kept by each subject throughout the study. Statistical comparisons were made by analysis of variance.

In the presence of misoprostol there was a 13% decrease in the area under the plasma concentration‐time curve of indomethacin over one dosing interval on Day 1 (P < 0.01), and at steady state there was a 24% decrease in the maximum plasma concentration (P < 0.02). The pharmacokinetics of indomethacin were not affected by co‐administration of ranitidine. Accumulation of indomethacin after repeated oral dosing was not significantly altered by the co‐administration of either misoprostol or ranitidine. The frequency and severity of abdominal symptoms was significantly increased (P < 0.01) during misoprostol dosing, compared with either ranitidine or placebo plus indomethacin. When the dosing phase (Days 1–8) was compared with the washout phase (Days 9–15) in each period, misoprostol, but not ranitidine or placebo, plus indomethacin resulted in an increase (P < 0.001) in abdominal symptom severity, frequency of bowel motions and a decrease in faecal consistency.
Oral pharmacokinetics of cyclosporin in patients with primary biliary Cirrhosis and patients with skin diseases
Authors: BEUKERS R. , RAVE S. DE , BERG J. W. O. VAN DEN , SCHALM S. W.
Published: July 2010

The pharmacokinetics of cyclosporin after oral administration were studied in seven patients with non‐end stage primary biliary cirrhosis (PBC) without previous cyclosporin treatment (Group I), a control group of nine patients with skin diseases (mainly psoriasis; Group II) and six patients with PBC after prolonged cyclosporin treatment (Group III). Whole blood concentrations of cyclosporin were measured using a nonspecific (N) radioimmunoassay (RIA) and — in a majority of the cases—also by a RIA specific (S) for the parent drug. No difference in cyclosporin absorption was observed between patients with PBC and those with a skin disease. The mean values for the area under the blood concentration‐time curve for the first 6 h after the test dose (AUC0‐6) and the maximal blood concentrations (Cmax) were significantly higher for Group I compared with Group II patients (P= 0.007 and 0.03, respectively), but the time to maximal blood concentrations (tc, max) did not differ. There was a trend toward higher mean AUC0‐6 (P= 0.08) and Cmax (P= 0.08) values for Group III compared with Group I patients. Tc, max values were not influenced by prolonged cyclosporin treatment. The ratio of cyclosporin whole blood concentrations measured by the non‐specific and specific RIA'S (N/S ratio) increased with time without obvious differences between the three groups. These data suggest that cyclosporin absorption and its biotransformation in the liver are not impaired in patients with non‐end stage PBC and that neither is affected by prolonged treatment.
Short report: comparison of the effects of sublingual nifedipine and isosorbide dinitrate on oesophageal emptying in patients with Chagasic achalasia
Authors: FIGUEIREDO M. C. A. , OLIVEIRA R. B. , IAZIGI N. , MATSUDA N. M.
Published: July 2010

The effects of sublingual nifedipine and isosorbide dinitrate on oesophageal emptying were compared in 11 patients with Chagasic achalasia. The oesophageal emptying of a radiolabelled test meal was assessed three times in each patient by a scintigraphic technique. No treatment preceded one of the studies (basal study). Nifedipine (20 mg) by the sublingual route 30 min before the meal, preceded one study. Isosorbide dinitrate, 5 mg by the sublingual route 5 min before the meal, preceded the third study. The order of the studies was allocated randomly for each patient. Oesophageal retention at the completion of the meal was significantly less (P < 0.01) after isosorbide dinitrate (median: 54%, range: 5–87%) than after sublingual nifedipine (median: 78%, range: 7–99%) or after the control study (median: 83%, range: 5–100%). This difference persisted up to 20 min after the meal. Values measured in the control study and after sublingual nifedipine were not different (P > 0.10).

These results show that isosorbide dinitrate, but not sublingual nifedipine, enhances oesophageal emptying in Chagasic achalasia.
The effect of combined therapy with ranitidine and pirenzepine in the treatment of reflux oesophagitis
Authors: LONDONG W. , PHILLIPS J. , JOHNSON N. J. , WOOD J. R.
Published: July 2010

The combination of a histamine H2‐receptor antagonist and a muscarinic receptor antagonist has been reported to result in greater suppression of intragastric acidity than either agent alone. The present randomized, double‐blind, multicentre trial compared the effects of the oral combination of 150 mg ranitidine b.d. plus 50 mg pirenzepine b.d. with 150 mg ranitidine b.d. plus placebo pirenzepine b.d. in the treatment of patients with reflux oesophagitis. All 157 patients had symptoms of gastro‐oesophageal reflux with endoscopically confirmed oesophageal erosions (Savary and Miller grades I‐III). After four weeks of treatment, healing rates were 32/75 (43%) in the combined treatment group and 34/76 (45%) in the group receiving ranitidine alone. After eight weeks, the cumulative healing rates had increased to 48/72 (67%) and 51/75 (68%), respectively. More patients receiving ranitidine plus pirenzepine had complete relief of day‐ and night‐time heartburn after four weeks compared with those receiving ranitidine alone (day: 59% vs. 38%, P= 0.02; night: 69% vs. 52%, P= 0.04). After eight weeks, symptom relief was comparable in both groups. Clinical adverse effects were reported by nine patients receiving ranitidine and by 19 patients receiving the combination. It is concluded that combining ranitidine with pirenzepine does not aid the healing of reflux oesophagitis but does improve symptom relief at four weeks.
Review article: urease, gastric ammonium/ammonia, and Helicobacter pylori — the past, the present, and recommendations for future research
Authors: GRAHAM D. Y. , GO M. F. , EVANS D. J.
Published: July 2010

The presence of ammonium in gastric contents was described in 1852; urease activity in the stomach was identified 70 years later. The discovery of gastric urease resulted in intense research activity to discover its origin, function, and relation to the gastric levels of ammonium and urea. Interest in urease waned in the 1960s as most pertinent questions appeared to have been addressed and there was strong evidence that gastric urease was not a property of the stomach but was of microbial origin. Identification of Helicobacter pylori as the source of urease in the stomach in the last decade has resulted in a rebirth of interest in gastric urease and its products.1–15 There is little actual evidence to support a role for toxicity of ammonia in relation to H. pylori and the bulk of the evidence suggests that the products of urease activity are not toxic and may even be beneficial. The purpose of this review is to examine the older literature and to examine‐ new findings in the perspective of what is already known and to suggest areas remaining to be examined. We ask, ‘What is old, what is new, and what needs to be done?’
Effect of sumatriptan, a new selective 5HT1‐like agonist, on liquid gastric emptying in man
Authors: HOUGHTON L. A. , FOWLER P. , KEENE O. N. , READ N. W.
Published: July 2010

Paired studies were carried out on 12 healthy male subjects to compare the effect of intravenous doses of the 5‐HT1‐like agonist sumatriptan (GR43175; 3 mg), 10 mg metoclopramide and saline control on the rate of gastric emptying of a radiolabelled liquid test‐meal. Intravenous administration of metoclopramide accelerated gastric emptying by decreasing the lag period, while intravenous administration of sumatriptan delayed gastric emptying by increasing the lag period. The observation that sumatriptan causes a delay in gastric emptying in normal healthy volunteers, but relieves nausea and vomiting during migraine attacks, suggests that sumatriptan may be acting via a central mechanism to relieve symptoms of nausea and vomiting associated with migraine.
Maintenance therapy in duodenal and gastric ulcer disease: survey of practice amongst British gastroenterologists
Authors: BOYD E. J. S. , PENSTON J. G. , WORMSLEY K. G.
Published: July 2010

We have used a postal questionnaire to obtain data on the practice of maintenance therapy for peptic ulcer disease by members of the British Society of Gastroenterology. Completed questionnaires were returned by 434 members. Ninety‐six per cent used maintenance therapy for patients with duodenal ulcer and 81 % for gastric ulcer. Maintenance therapy was considered to be safe (duodenal ulcer 91%; gastric ulcer 78%), acceptable to patients (duodenal ulcer gastric ulcer 89%; gastric ulcer 80%) and to reduce the incidence of ulcer complications (duodenal ulcer 81 %; gastric ulcer 68 %). There was consensus that increasing age of patient, current use of non‐steroidal anti‐inflammatory drugs, previous ulcer complications, and ulcer relapse after surgery were relatively strong indications for maintenance therapy. However, the proportion of patients who received maintenance therapy varied widely amongst respondents (from < 10% to > 50%). There was no agreement on the optimal duration of therapy, nor on management of patients who relapsed during maintenance therapy. It appears that the criteria for use of maintenance therapy need to be better defined, and that established knowledge about the practice of maintenance therapy should be better disseminated and acted upon.
Short report: omepmzole plus antibiotic combinations for the eradication of metronidazole‐resistant Helicobacter pylori
Authors: BELL G. D. , POWELL K. U. , BURRIDGE S. M. , SPENCER G. , BOLTON G. , PURSER K. , BROOKS S. , PROSSER S. , HARRISON G. , GANT P. W. , JONES P. H. , TROWELL J. E.
Published: July 2010

Twenty‐eight Helicobacter pylori‐positive patients with metronidazole‐resistant isolates and 25 with metronidazole‐sensitive isolates were treated for 14 days with 40 mg omeprazole nocte plus 500 mg amoxycillin t.d.s. Eradication of H. pylori, defined as absence of the organism one month after cessation of treatment, was assessed using the [14C]urea breath test. The eradication rate in patients with metronidazole‐resistant isolates was 14/28 (50%) while that in patients was metronidazole‐sensitive isolates was 12/25 (48%). In contrast to these encouraging eradication rates, very poor results were obtained with a 7‐day course of omeprazole (40 mg nocte) in combination with erythromycin ethylsuccinate (500 mg q.d.s.) and tripotassium dicitrato bismuthate tablets (120 mg q.d.s.). The latter eradication rates were 3/20 (15%) in patients taking erythromycin tablets and 3/19 (16%) in those taking a liquid formulation of erythromycin. All treatment regimens were well tolerated and all patients completed the prescribed course of therapy.
Omeprazole is superior to ranitidine plus metoclopramide in the short‐term treatment of erosive oesophagitis
Authors: ROBINSON M. , DECKTOR D. L. , MATON P. N. , SABESIN S. , ROUFAIL W. , KOGUT D. , ROBERTS W. , McCULLOUGH A. , PARDOLL P. , SACO L. , RUSTGI V. , KOVACSHU T.
Published: July 2010

Histamine H2‐receptor antagonists are moderately effective in symptomatic treatment and healing of erosive oesophagitis, but they are not as effective as the proton pump inhibitor omeprazole. In some studies prokinetic agents seem to increase the effectiveness of H2‐antagonists, but no study comparing the efficacy of omeprazole to H2‐antagonists plus prokinetic agents has been performed. The purpose of this study was to compare the efficacy and tolerability of 20 mg omeprazole daily with 150 mg ranitidine b.d.s. plus the prokinetic agent 10 mg metoclopramide q.d.s. in patients with erosive oesophagitis. After both 4 and 8 weeks of treatment, omeprazole healed the mucosa in significantly more patients than did ranitidine plus metoclopramide. Omeprazole also provided significantly greater relief from daytime heartburn, nighttime heartburn, and acid regurgitation, and was associated with decreased concomitant antacid use. Although the overall incidence of adverse events was similar in the two treatment groups, a significantly higher number of treatment‐related adverse events and more treatment‐related withdrawals from the study occurred in the ranitidine plus metoclopramide treatment group. Omeprazole is more effective and better tolerated than the combination of standard dose ranitidine plus metoclopramide for patients with erosive oesophagitis.
Review article: immunosuppressive therapy for inflammatory bowel disease
Authors: KOZAREK R. A.
Published: July 2010

Refractory inflammatory bowel disease can be treated by surgery or using nutritional supplementation or replacement. Immunosuppressive agents may also play a role for refractory disease; they have gained widespread acceptance, due not only to trials that demonstrate efficacy but also to the realization that
Review article: topical corticosteroids in inflammatory bowel disease
Authors: MULDER C. J. J. , TYTGAT G. N. J.
Published: July 2010

It would be ideal to treat inflammatory bowel disease with topical corticosteroids that are either not absorbed through the mucosa, or have a substantial first‐pass hepatic metabolism. The topical use of hydrocortisone, prednisolone‐21‐phosphate or betamethasone is often associated with systemic side‐effects. Newer corticosteroid preparations (prednisolone metasulphobenzoate, tixocortol pivalate, fluticasone propionate, beclomethasone dipropionate and budesonide) are usually associated with minimal systemic corticosteroid activity. This article reviews the clinical activity and safety of these newer preparations.
Efficacy of long‐term therapy with low doses of omeprazole in the control of gastric acid secretion in Zollinger‐Ellison syndrome patients
Authors: CORLETO V. , ANNIBALE B. , D'AMBRA G. , SAGGIORO A. , FERRUA B. , CASSETTA M. R. , DELLE FAVE G.
Published: July 2010

Thirteen patients with Zollinger‐Ellison syndrome were investigated: 8 without, and 5 with, previous gastric surgery. After 7–34 months of treatment with famotidine, 8 out of 13 patients were resistant to this drug. Omeprazole 60 mg/day was administered to these 8 patients; after one month, the dose was reduced to 40 mg/day, and after another month to 20 mg/day. Basal acid secretion was inhibited by every dose of omeprazole. The patients were then treated with a low dose (20 mg/day) of omeprazole for a longer period. Periodic clinical and endoscopic assessments, and measurement of basal acid secretion showed the efficacy of this low dose of omeprazole in our Zollinger‐Ellison syndrome patients. The drug was discontinued after 12–32 months of omeprazole treatment, and gastric acid recovery was evaluated. Four patients recovered 50% of their ‘initial basal acid secretion’ after 5 days, while two patients who had been treated with omeprazole for a longer time (30–32 months) recovered only 38 and 40%, respectively, of their ‘initial basal acid secretion’ at the tenth day. Our results indicate that the omeprazole dosage to be used in the treatment of Zollinger‐Ellison syndrome must be chosen principally on the basis of basal acid secretion determination. A low daily dose of omeprazole is able to control acid secretion in Zollinger‐Ellison syndrome for a long period (10–30 months). The slow recovery of gastric secretory function demonstrates the prolonged inhibitory effects of omeprazole.
Short report: effect of ranitidine on duodenal ulcer healing in patients with cirrhosis of the liver
Authors: LJUBIĆIĆ W. , BILIĆ A. , ROIĆ D.
Published: July 2010

The effect of ranitidine (300 mg daily) on the healing of acute duodenal ulcer was investigated in patients with and without cirrhosis of the liver. Of the 109 patients who entered the study, two patients from each group were excluded. Healing rates after 4 and 8 weeks were significantly different between patients with cirrhosis and controls (4‐ and 8‐week healing rates in cirrhotics and non‐cirrhotics: 49 and 69%, and 71 and 91%, respectively). This study demonstrates that duodenal ulcer healing is delayed in patients with cirrhosis.
Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease
Authors: BRIGNOLA C. , BELLOLI C. , DE SIMONE G. , EVANGELISTI A. , PARENTE R. , MANCINI R. , IANNONE P. , MOCHEGGIANI E. , FABRIS N. , MORINI M. C. , LICASTRO F.
Published: July 2010

The aim of this work was to evaluate whether oral supplementation with zinc sulphate (ZnSO4) could restore thymic endocrine function in patients with Crohn's disease who showed decreased plasma concentrations of zinc and active thymulin, a zinc‐dependent thymic hormone. Twenty‐seven patients in clinical remission were randomly assigned to receive, for 3 months, one of the following treatments: 60 mg/day ZnSO4; 200 mg/day ZnSO4 or placebo. Plasma thymulin activity and zinc concentrations significantly increased only in patients treated with 200 mg/day ZnSO4. Lymphocyte subpopulations, within the range of normality before zinc supplementation, were unaffected by any of the administered treatments. In conclusion, low plasma concentrations of zinc and thymulin in Crohn's disease patients were restored by the administration of high doses of zinc.
Effect of zinc therapy on natural killer cell activity in inflammatory bowel disease
Authors: VAN DE WAL Y. , VEER A. VAN DER SLUYS , VERSPAGET H. W. , MULDER T. P. J. , GRIFFIOEN G. , VAN TOL E. A. F. , PEÑA A. S. , LAMERS C. B. H. W.
Published: July 2010

Disturbances in zinc metabolism have been documented in patients with inflammatory bowel disease. In this study we evaluated the effect of in vivo treatment with zinc on the in vitro natural killer cell activity in thirteen inflammatory bowel disease patients, with stable disease and mild–moderate disease activity, in a double‐blind randomized cross‐over trial. The results of our study show a long‐lasting effect of in vivo zinc administration, which decreased peripheral blood natural killer cell activity in inflammatory bowel disease.
Barrett's oesophagus—cancer risk, biology and therapeutic management
Authors: FENNERTY M. B. , SAMPLINER R. E. , GAREWAL H. S.
Published: July 2010

Barrett's oesophagus is receiving increasing scrutiny as the rates of adenocarcinoma of the oesophagus rise. Because clinical features are not predictive of the presence of Barrett's oesophagus and most individuals with Barrett's oesophagus go undetected, a case can be made for surveillance endoscopy in patients with chronic reflux. Once Barrett's oesophagus is diagnosed patients should be entered into a surveillance programme despite lack of proof of efficacy. Scientific study of putative biological markers of increased risk has added dramatically to the understanding of the biology of the lesion, but currently the finding of high‐grade dysplasia remains the best marker predicting the presence of greatly increased risk of developing cancer. It is likely that newer molecular biology techniques will become clinically applicable biological markers in the future. Currently there is no effective medical nor surgical therapy to cause regression of the metaplastic Barrett's epithelium, however the application of novel de‐differentiating agents or ablation of the metaplastic epithelium while controlling oesophageal acid exposure and other environmental abnormalities offer hope that effective treatment of Barrett's oesophagus may someday be reality.
Relapse rate of patients after healing of oesophagitis—a prospective study of alginate as self‐care treatment for 6 months
Authors: POYNARD T. ,   French Co‐operative Study Group
Published: July 2010

In order to estimate the rate of symptomatic relapse and to identify factors associated with this relapse, 1030 patients were included in a multicentre study. All patients included had clinically and endoscopically healed oesophagitis (grade I (erosion, 57%), grade II (confluent erosion, 33%) or grade III (circular erosion, 9%)) after treatment with an H2 blocker or omeprazole. Patients were given conservative advice and were told to take sodium alginate only in response to pain. Relapse was defined as pain justifying more than eight sodium alginate sachets over 48 hours or treatment with another drug, or the need for a new endoscopy. Forty risk factors were recorded initially and patients were seen every 2 months; they filled out diary‐cards describing symptoms and drug consumption. Data were available for 883 patients during follow up. The cumulative percentage of patients without relapse at 6 months estimated by Kaplan Meier method was 76 ± 2 % (mean ± S.E.M.). Among these patients without relapse, 95% took less than two sachets per day. Only two factors were identified as associated with relapse—the grade of oesophagitis (P < 0.007), and the occurrence of stress during follow‐up (P < 0.05). The percentage of patients free from relapse at six months was 85 ± 2% in patients with grade I oesophagitis, 69 ± 3% in patients with grade II, and 56 ± 6% in patients with grade III oesophagitis (P < 0.0001).
Trends in morbidity and mortality from peptic ulcer disease: Tayside versus Scotland
Authors: PENSTON J. G. , CROMBIE I. K. , WAUGH N. R. , WORMSLEY K. G.
Published: July 2010

Recent studies have shown that the prophylactic use of H2‐receptor antagonists reduces both ulcer recurrence and the risk of ulcer complications. Despite these results, epidemiological studies have failed to show any evidence of an effect of gastric anti‐secretory drugs on complicated ulcer disease in the community.

Since 1979, it has been the policy of the gastroenterology department at Ninewells Hospital in Tayside to recommend long‐term, continuous therapy with H2‐receptor antagonists for patients with peptic ulcer; in contrast, prophylactic therapy is less commonly used in the rest of Scotland. The difference in the management of peptic ulcer between Tayside and Scotland presented an opportunity to study the population effects of the widespread use of continuous H2‐receptor antagonists on the morbidity and mortality from ulcer disease. This study compared the trends in hospital admissions, gastric surgery, haemorrhage, perforation and mortality from ulcer disease using data supplied by the Information and Statistics Division of the Common Services Agency, Scottish Health Service, Edinburgh.

During the 1980s, hospital admissions for peptic ulcer declined significantly in Tayside, whereas in Scotland there was no obvious downward trend. Gastric surgery for ulcer disease declined throughout Scotland although the fall was significantly steeper in Tayside than in the rest of Scotland. For the population in general, the rate of perforation decreased faster in Tayside than in the rest of Scotland, although the difference was not significant. The rate of admissions for ulcer haemorrhage declined substantially in Tayside whereas there was little change in Scotland as a whole. The decrease in mortality from ulcer disease in all groups except younger females was more marked in Tayside than in Scotland, although the differences were not significant.

The magnitude of the differences between Tayside and Scotland, and in particular the consistency of these results across a broad range of indicators of ulcer disease, suggests that the policy of prescribing long‐term, continuous therapy with H2‐ receptor antagonists has reduced both uncomplicated and complicated peptic ulcer in the community in Tayside.
Comparison of two intravenous ranitidine regimens in a homogeneous population of intensive care unit patients
Authors: GEUS W. P. , VINKS A. A. T. M. M. , SMITH S. J. , WESTRA P. , LAMERS C. B. H. W.
Published: July 2010

Primed continuous infusion and repeated intravenous injections of ranitidine (daily dose 200 mg) were compared in a homogeneous population of postoperative intensive care unit patients in a randomized fashion. Intragastric pH was measured continuously for 72–96 h with combined glass electrodes positioned in the gastric corpus. Patients whose intragastric acidity fell below pH 4.0 for 70% of a 24‐h period within 48 h after the operation (baseline period) were considered ‘at risk’ of developing stress‐related lesions. From the 26 patients screened, 18 fulfilled this criterion. Nine received the continuous infusion regimen (50 mg bolus+0.125 mg.kg/h) and nine received repeated boluses (50 mg ranitidine every 6 h). A consistent decrease of intragastric acidity was shown in each group by a rise in 24‐h median pH from 1.4 (1.3–1.7; 26th–75th percentile) during the baseline period to 4.2 (1.9–5.4, P < 0.01) for the continuous infusion and from 1.55 (1.1–2.2) to 2.65 (2.1–3.5, P < 0.02) for the repeated boluses during the final 24 h of the therapy period. During that period intragastric pH was maintained above 4 for 52% of time by continuous infusion and for 40% of time for repeated boluses compared with 10.8% (P= 0.01) and 6.2% (P= 0.008) of time, respectively, in the baseline period. In conclusion, although no statistically significant differences between the two regimens could be detected, the continuous infusion regimen tended to show slightly better results in percentages of time that pH values were above 1 to 7, and in median 24–h pH values.
Ranitidine bismuth citrate and aspirin‐induced gastric mucosal injury
Authors: HUDSON N. , MURRAY F. E. , COLE A. T. , TURNBULL G. M. , LETTIS S. , HAWKEY C. J.
Published: July 2010

The aim of this study was to investigate the protective action of a new compound, ranitidine bismuth citrate, in the prevention of aspirin‐induced acute mucosal injury to the upper gastrointestinal tract of healthy human volunteers. In a double‐blind randomized three‐way cross‐over study 24 male volunteers received placebo, 900 mg aspirin or 900 mg aspirin and 800 mg ranitidine bismuth citrate at 12‐h intervals for nine doses with a 2‐week wash‐out period between each treatment. The median (interquartile range) number of erosions seen at endoscopy when ranitidine bismuth citrate was given with aspirin (1 [0–4]) was significantly lower than aspirin alone (24 [16–32]) (P < 0.001) and not significantly different from either baseline or placebo (0 [0–2]). These findings were similarly reflected in the effects on microbleeding following the ninth dose: 12.1 (7.1–21.0) μL/10 min following aspirin alone compared to levels with placebo of 1.2 (0.4–2.9), and with aspirin and ranitidine bismuth citrate of 1.6 (0.8–2.6) (P < 0.005). Ranitidine bismuth citrate conferred substantial protection from aspirin‐induced injury to the gastric and duodenal mucosa as determined by both endoscopic assessment and microbleeding rates, reducing injury to placebo levels.
Effect of a 5HT3‐antagonist (ondansetron) on rectal sensitivity and compliance in health and the irritable bowel syndrome
Authors: HAMMER J. , PHILLIPS S. F. , TALLEY N. J. , CAMILLERI M.
Published: July 2010

In some patients with the irritable bowel syndrome, rectal urgency and discomfort are major clinical problems and, under experimental conditions, these symptoms are perceived at lesser volumes of rectal distension than they are in asymptomatic controls. Further, a 5‐hydroxytryptamine type‐3 receptor antagonist increased the threshold for rectal discomfort in irritable bowel syndrome. Our aims were, (a) to measure rectal sensation during isobaric distensions of the rectum, and (b) to test the effect of another selective 5HT3antagonist, ondansetron 0.15 mg/kg, on rectal sensitivity, colonic tone, rectal tone and manometric responses. Ten healthy volunteers and five patients with diarrhoea‐predominant irritable bowel syndrome were studied. A multilumen barostatmanometric assembly was placed in the descending colon, and a second barostat balloon was positioned in the rectum. Tone in the wall of the colon and rectum was measured by the barostat balloon volume during a constant pressure clamp, while intraluminal pressures were recorded by manometry; perceived sensations were also recorded before and after the intravenous administration of ondansetron or placebo in blinded fashion. Rectal resistance to stretch was greater and rectal urgency was induced by lower distending pressures in irritable bowel syndrome, however, basal tone in the rectum was similar in health and irritable bowel syndrome. Ondansetron did not change rectal sensitivity (first sensation or urgency) or tone. Rectal distension did not alter tone in the descending colon or colonic manometry; ondansetron did not influence any index of colonic function. We conclude that in diarrhoea‐predominant irritable bowel syndrome there is reduced rectal compliance and the rectum is abnormally sensitive to a pressure stimulus, but this is not altered by 5HT3‐blockade with ondansetron at the dose used.
An investigation into the effect of cimetidine pre‐treatment on raft formation of an anti‐reflux agent
Authors: WASHINGTON N. , WILSON C. G. , WILLIAMS D. L. , ROBERTSON C.
Published: July 2010

It is now becoming common practice to co‐administer H2 receptor antagonists and anti‐reflux agents in the treatment of reflux oesophagitis. The mechanism by which anti‐reflux agents achieve flotation requires a small amount of gastric acid to be present in the stomach. This study investigated whether an antireflux agent would remain effective after the decrease in acid secretion produced by a typical clinical dosage regimen of cimetidine (400 mg q.d.s., 7 days). Gastric distribution and residence of a meal and an anti‐reflux agent were assessed in 12 normal subjects using gamma scintigraphy. The area under the gastric and fundal emptying curves demonstrated that Liquid Gaviscon (sodium alginate compound) had a significantly greater gastric residence than the meal, both during the control period and after cimetidine pre‐treatment, and that the majority of the Gaviscon was located in the fundus. The distribution of Gaviscon into the fundus was not affected by cimetidine pre‐treatment. Cimetidine pre‐treatment slightly, but not significantly, increased the time for half the meal and the Gaviscon to empty from the stomach. The results suggest that the mechanism of action of Liquid Gaviscon is not compromised by concurrent H2‐antagonist therapy.
Treatment of active distal ulcerative colitis with immunoglobulin G enemas
Authors: JARLØV A. E. , MUNKHOLM P. , SCHMIDT P. NORDBLAD , LANGHOLZ E. , VESTERGAARD B. FABER , BECH R. MøLSKOV
Published: July 2010

Seven patients with active distal ulcerative colitis were treated with IgG enemas given as a daily bedtime retention enema for two weeks. Evaluation of effect was assessed by means of sigmoidoscopy with biopsy, measuring acute phase reactants in peripheral blood, and measuring the faecal protein loss. Clinical signs of active disease were registered by the patients on a diary chart. Five patients completed the treatment period, two patients were withdrawn after 7 and 10 days due to deterioration of disease. Four patients did not register any effect, whereas one patient improved clinically. In conclusion, rectally administered IgG did not exert any effect on rectal ulcerative colitis in our study.
Oral budesonide in active Crohn's disease
Authors: LÖFBERG R. , DANIELSSON Å. , SALDE L.
Published: July 2010

We studied the efficacy and safety of the topically acting steroid budesonide in an oral preparation for controlled ileal release in an open, uncontrolled trial. Twenty‐one patients with active Crohn's disease localized to the distal ileum, ileocaecal region or ascending colon, entered the trial. The median age was 36 years and the median duration of Crohn's disease was 8 years. The patients received budesonide, in a controlled ileal release preparation, in a dose of 3 mg t.d.s. for 12 weeks, followed by a reduction to 2 mg t.d.s. for 6 weeks and finally to 1 mg t.d.s. for an additional 6 weeks. Primary variables were the modified Crohn's disease activity index (mCDAI), laboratory parameters and plasma cortisol levels. The mean mCDAI at entry was 268 (± 71 s.d.). dropping to 146 (± 91 s.d.) after 4 weeks of treatment and to 122 (± 87 s.d.) after a total of 12 weeks on 3 mg t.d.s. (P < 0.001). Following dose reduction, the mean mCDAI increased after 18 and 24 weeks of treatment. The erythrocyte sedimentation rate also fell significantly during the study period. Eighteen patients responded favourably during the first 12‐week treatment period, and 13 completed the trial. Seven patients were withdrawn due to failure of treatment after reduction of dose, and four of those were treated surgically. No serious side‐effects or significant corticosteroid‐related side‐effects occurred. The mean plasma cortisol levels decreased, but remained within normal range. Four patients were markedly suppressed on the highest dose of budesonide. The controlled ileal release of budesonide seems to be beneficial in active ileal and ileocolonic Crohn's disease without causing important side‐effects.
Cisapride increases gallbladder volume in gallstone patients before and after extracorporeal shock wave lithotripsy
Authors: ZIEGENHAGEN D. J. , HEITZ W. , KRUIS W. , POHL C. , ZEHNTER E.
Published: July 2010

We have previously shown that oral cisapride causes a dose‐related increase of fasting gallbladder volume in healthy subjects. The present study investigates the effect of cisapride on gallbladder motility in 16 patients with gallbladder stones: 8 patients had no biliary symptoms, but the other 8 patients with symptomatic gallstone disease were studied before and 6 weeks after extracorporeal shock wave lithotripsy (ESWL). For each study the patients received a single oral dose of 20 mg cisapride; fasting gallbladder volume was measured by ultrasound before, and for 120 minutes after, drug administration. In the 8 asymptomatic patients a mean maximal increase of the fasting volume to 152.7 ± 7.6% of the initial value was observed at a mean 97.5 ± 8.3 minutes after cisapride ingestion. Similarly, in the 8 patients with biliary pain mean fasting volume after cisapride ingestion increased to 141.3 ± 5.7% before ESWL treatment and to 145.0 ± 5.8% after ESWL and 6 weeks of oral litholytic therapy. There were no significant differences between the results in the symptomatic and asymptomatic patients. Our results indicate that cisapride increases the gallbladder volume in gallstone patients regardless of biliary symptoms. Similar volume changes were observed before therapy and after ESWL with bile acid therapy. The therapeutic efficacy of litholytic agents could be diminished by simultaneous cisapride administration.
Regression of columnar lined (Barrett's) oesophagus with continuous omeprazole therapy
Authors: GORE S. , HEALEY C. J. , SUTTON R. , EYRE‐BROOK I. A. , GEAR M. W. L. , SHEPHERD N. A. , WILKINSON S. P.
Published: July 2010

Twenty‐three adult patients with a columnar lined (Barrett's) oesophagus are being treated with long‐term omeprazole, 40 mg daily. Twelve had never undergone anti‐reflux surgery (Group 1), the other eleven having previously had insertion of an Angelchik anti‐reflux prosthesis (Group 2). Endoscopy was carried out six months before, immediately before and six months, one year and two years into treatment. Multiple and standardized biopsies were taken at each endoscopy. Results from the two groups were similar. During the 6‐month run‐in period there was a statistically non‐significant increase in the linear extent of the columnar mucosa, but this showed a progressive, statistically significant decrease during the two years of treatment. Other evidence for regression of the Barrett's mucosa includes the emergence of large numbers of macroscopic squamous islands within the abnormal mucosa, an increase in the number of microscopic squamous islands, and microscopic squamous encroachment of the abnormal mucosa at the squamocolumnar junction. Histological assessment showed a reduction in the proportion of sulphomucin‐rich intestinal metaplasia, but this only achieved statistical significance in Group 1. The results substantiate the importance of acid in the pathogenesis of Barrett's oesophagus. Omeprazole may have a therapeutic role in bringing about regression of the metaplastic epithelium.
Safety of lansoprazole
Authors: COLIN‐JONES D. G.
Published: July 2010

The care with which patients are monitored during clinical trials provides an excellent database to assess the tolerability and safety of drugs. Additional information can be obtained from knowledge of the compound itself, its metabolism and its pharmacological action. Other compounds from the same class can highlight areas that need particular study. All these factors have been used to assess the safety of lansoprazole. Lansoprazole has been administered to 4749 subjects and has been well tolerated. Only 1.2% of patients have been withdrawn from trials because of suspected drug‐related events but there was no pattern and no relationship to drug dosage. Diarrhoea (3.2%) and headache (4.7%) were the most commonly reported adverse events.
Future prospects for proton pump inhibitors
Authors: FRESTON J. W.
Published: July 2010

Future prospects for proton pump inhibitors depend on their efficacy and safety relative to H2‐receptor antagonists, the therapeutic standard for acid peptic disorders. As safety concerns diminish, efficacy considerations become more important as these may pertain to cost effectiveness. Comparative, controlled trials show that omeprazole and lansoprazole are somewhat more effective than H2‐blockers in healing duodenal and gastric ulcers, providing faster relief of symptoms. Relapse after cessation of therapy is similar between the two classes. The proton pump inhibitors are substantially more effective in healing lesions and relieving symptoms in patients with reflux oesophagitis, and are particularly effective in cases that have failed to heal after 12 weeks of treatment with H2‐blockers. Relapse rates of oesophagitis are significantly less with prolonged treatment with omeprazole than ranitidine. A proton pump inhibitor combined with amoxicillin is less effective than triple therapy with antibiotics and bismuth in eradicating Helicobacter pylori infections, but is more convenient and associated with fewer side‐effects. Efficacy might be improved by more optimal dosing regimens. Prospects for reversible proton pump inhibitors depend on the balance between their theoretical advantages and their acid inhibition profile which, at present, closely resembles that of H3‐bIockers.
Three months of octreotide treatment decreases gastric acid secretion and argyrophil cell density in patients with Zollinger‐Ellison syndrome and antral G‐cell hyperfunction
Authors: ANNIBALE B. , FAVE G. DELLE , AZZONI C. , CORLETO V. , CAMBONI G. , D'AMBRA G. , PILATO F. P. , BORDI C.
Published: July 2010

Methods: The effects of three months of treatment with octreotide on gastric acid hypersecretion induced by hypergastrinaemia were investigated in patients with Zollinger‐Ellison syndrome (n= 5) or antral G‐cell hyperfunction (n= 4). Gastric acid secretion, fasting plasma gastrin concentrations and clinical findings were examined, and a morphometrical analysis of oxyntic endocrine cells was performed.

Results: Administration of octreotide 100 meg b.d. subcutaneously significantly decreased the volume density of argyrophil cells (P < 0.05) as well as basal and pentagastrin‐stimulated acid secretion (P < 0.05). Although partial or complete loss of inhibition was found in most patients after 3 months, gastrin levels were decreased during the first 2 months of treatment (P < 0.05). Fundic D‐cells were not affected by treatment. Positive correlations were observed between volume density of argyrophil cells and basal acid output (r= 0.65); plasma gastrin and basal acid output (r= 0.74); plasma gastrin concentrations and volume density of argyrophil cells (r= 0.80).

Conclusion: These results support the important role of the enterochromamn‐like cell in maintaining acid secretion, and indicate a specific role for octreotide in the therapy of gastric acid hypersecretion associated with hypergastrinaemic diseases.
Effect of eradication of Helicobacter pylori on gastric epithelial cell proliferation
Authors: FRASER A. G. , SANKEY R. SIM. E. A. , DHILLON A. P. , POUNDER R. E.
Published: July 2010

Background: Helicobacter pylori is associated with B‐type gastritis, duodenal ulcer disease, and possibly gastric carcinoma. The object of this study was to assess the effect of eradication of H. pylori infection on gastric epithelial cell proliferation.

Methods: Gastric epithelial cell proliferation was assessed in 22 H. pyloori‐positive duodenal ulcer patients before and 6 weeks after' triple therapy’with bismuth, tetracycline and metronidazole. Cell proliferation was studied either by immunostaining for the proliferating cell nuclear antigen (PCNA) or by a microdissection technique.

Results: Eradication was successful in 10 of the 22 H. pylori‐positive patients. Treatment with' triple therapy’resulted in a significant fall in the rate of gastric epithelial cell proliferation; this effect was seen in both the gastric body and antrum. There was a significant correlation between the number of PCNA‐labelled cells and the histological grade of activity (neutrophil inflammation) (r= 0.49, P= 0.02); the same correlation was found for the number of mitoses per gland (r= 0.5, P= 0.02). There was no significant difference in the treatment effect for eradicated or non‐eradicated patients or either the body or antrum. Six patients, who had at least one antral biopsy that showed evidence of focal intestinal metaplasia, had a higher rate of cell proliferation.

Conclusions: The reduction in epithelial cell proliferation in the body and antrum after triple therapy is independent of successful eradication of H. pylori, and it may be due to an anti‐inflammatory effect of triple therapy.
Phospholipase A2 activity in gastric juice from patients with active and H. pylori‐eradicated healed duodenal ulcer
Authors: BERSTAD K. , SJÖDAHL R. , BERSTAD A.
Published: July 2010

Background: Despite the close association between gastric Helicobacter pylori infection and duodenal ulcer. little is known about how this organism may promote mucosal damage. A possibility might be that it produces, or induces the host to release, phospholipases that metabolize the protective layer of phospholipids

Methods: Aimed at determination of phospholipase A2 activity and the concentration of choline‐containing phospholipids in gastric juice, aspirates were collected during gastroscopy in 38 consecutive referrals with either active (n= 19) or H. pylori‐eradicated healed duodenal ulcer (n = 19).

Results: Gastric juice phospholipase A2 activity was 3.1 times higher in active than in healed duodenal ulcers (P = 0.03). Concurrently, the concentration of choline‐containing phospholipids in the group with active ulcers was less than half compared with the healed group (P = 0.02).

Conclusion: The results indicate that phospholipase A2 activity and the concentration of choline‐containing phospholipids in gastric juice are related to H. pylori status and duodenal ulcer disease.