bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium polycarbophil compared with placebo in irritable bowel syndrome
Authors: TOSKES P. P. , CONNERY K. L. , RITCHEY T. W.
Published: July 2010

Calcium polycarbophil was compared with placebo in 23 patients with irritable bowel syndrome in a six‐month, randomized double‐blind crossover study. Patients received polycarbophil tablets at a dosage of 6 g/day (twelve 0.5‐g tablets) or matching placebo tablets. At study end, among patients expressing a preference, 15 of 21 (71%) chose polycarbophil over placebo for relief of the symptoms of irritable bowel syndrome. Statistically significant differences favouring polycarbophil were found among the following patient subgroups: 15 (79%) of 19 with constipation; all six with alternating diarrhoea and constipation; 13 (87%) of 15 with bloating; and 11 (92%) of 12 with two or more symptoms. Polycarbophil was rated better than placebo in monthly global responses to therapy. Patient diary entries showed statistically significant improvement for ease of passage with polycarbophil. Polycarbophil was rated better than placebo for relief of nausea, pain, and bloating. The data suggest that calcium polycarbophil can benefit irritable bowel syndrome patients with constipation or alternating diarrhoea and constipation and may be particularly useful in patients with bloating as a major complaint.
Short report: a non‐metronidazole triple therapy for eradication of Helicobacter pylori infection–tetracycline, amoxicillin, bismuth
Authors: GRAHAM D. Y. , LEW G. M. , RAMIREZ F. C. , GENTA R. M. , KLEIN P. D. , MALATY H. M.
Published: July 2010

Triple therapies using bismuth, metronidazole and tetracycline or amoxicillin were the first truly successful anti‐H. pylori therapies. Metronidazole resistance has become an increasing problem that has severely limited the usefulness of the original triple therapy. Resistance to tetracycline or amoxicillin has not been reported and both are effective against H. pylori. We therefore tested a new triple therapy consisting of 500 mg tetracycline, 500 mg amoxicillin, and 2 tablets of bismuth subsalicylate each administered four times daily (with meals and at bedtime) for 14 days during treatment with ranitidine 300 mg daily. H. pylori eradication was defined as no evidence of H. pylori one or more months after stopping therapy. H. pylori status was evaluated by a combination of urea breath test and histology. Sixteen patients with H. pylori infection and active peptic ulcers were enrolled. The new triple therapy was successful in only 7 individuals (43%). Metronidazole appears to be critical for the effectiveness of the original triple therapy. An alternative to metronidazole will be required for a new successful triple therapy.
Review article: Lack of clinical significance of the interaction between H2‐receptor antagonists and ethanol
Authors: LEVITT M. D.
Published: July 2010

It has been proposed that an appreciable fraction of ingested ethanol is metabolized in the gastric mucosa and that inhibition of this metabolism by H2‐receptor antagonists produces clinically important increases in blood ethanol. This paper reviews available data concerning gastric metabolism of ethanol and the influence of H2‐antagonists on ethanol metabolism. It concludes that very little, if any, metabolism of ethanol is likely to occur in the gastric mucosa, and the interaction between H2‐antagonists and ethanol is clinically insignificant.
The effects of lansoprazole, 30 or 60 mg daily, on intragastric pH and on endocrine function in healthy volunteers
Authors: DAMMANN H. G. , MÜHLEN A. VON ZUR , BALKS H. J. , DAMASCHKE A. , STEINHOFF J. , HENNIG U. , SCHWARZ J. A. , FUCHS W.
Published: July 2010

Seven days of dosing with either 30 mg or 60 mg of lansoprazole were compared with placebo in a double‐blind, randomized, three‐way cross‐over study in 12 male healthy volunteers. Twenty‐four‐hour intragastric pH was measured after 7 days of dosing with each regimen, as well as 3 and 7 days after the end of dosing. During dosing with placebo, intragastric pH was above 4 for a median of 51 minutes. pH values were significantly raised to above 4 for 8.45 and 8.33 hours on Day 7 of dosing with lansoprazole 30 and 60 mg, respectively, but returned to normal by the third day after stopping dosing. No clinically relevant influence on endocrine function (serum concentrations of insulin, aldosterone, testosterone, parathormone, glucagon, T3, T4, TSH, LH, FSH, STH. prolactin, circadian Cortisol profile, ACTH test) was observed. No serious adverse clinical or laboratory events were noted.
Gastric anti‐secretory, mucosal protective, anti‐pepsin and anti‐Helicobacter properties of ranitidine bismuth citrate
Authors: STABLES R. , CAMPBELL C. J. , CLAYTON N. M. , CLITHEROW J. W. , GRINHAM C. J. , McCOLM A. A. , McLAREN A. , TREVETHICK M. A.
Published: July 2010

Ranitidine bismuth citrate is a novel compound formed from ranitidine and a bismuth citrate complex. In conscious dogs, ranitidine bismuth citrate had similar activity to ranitidine hydrochloride as an inhibitor of histamine‐induced gastric acid secretion when oral doses containing equivalent amounts of ranitidine base (0.1 or 0.3 mg/kg) were compared. In the rat, ranitidine bismuth citrate (3–30 mg/kg p.o.) prevented gastric mucosal damage induced by ethanol (fundic damage) and indomethacin (antral damage).

Ranitidine hydrochloride and tripotassium dicitrato bismuthate were also effective against indomethacin induced damage, but were both significantly less potent than ranitidine bismuth citrate in this model.

Ranitidine hydrochloride was inactive against ethanol‐induced damage. In vitro, ranitidine bismuth citrate (1 mmol/L) inhibited human pepsin isoenzymes 1, 2, 3 and 5. Pepsin 1 was inhibited to a similar extent by ranitidine bismuth citrate, bismuth citrate and tripotassium dicitrato bismuthate at concentrations equivalent to 1 mmol/L bismuth, but ranitidine (1 mmol/L) was inactive. Ranitidine bismuth citrate was more potent than tripotassium dicitrato bismuthate as an inhibitor of pepsins 2, 3 and 5. Ranitidine bismuth citrate inhibited both Helicobacter pylori (effective concentration 4–32, μg bismuth/ml) and H. mustelae (1–4,μg bismuth/ml); similar results were obtained with tripotassium dicitrato bismuthate. Bismuth citrate was slightly less effective, and ranitidine hydrochloride was inactive (> 125, μg/ml). In ferrets naturally colonized with H. mustelae, oral treatment with ranitidine bismuth citrate, 12 or 24 mg/kg twice daily for 4 weeks, caused a dose related clearance of H. mustelae. Qualitatively similar results were obtained in a small study with tripotassium dicitrato bismuthate and bismuth citrate.
Prospective study of the need for long‐term antisecretory therapy in patients with Zollinger—Ellison syndrome following successful curative gastrinoma resection
Authors: METZ D. C. , BENYA R. V. , FISHBEYN V. A. , PISEGNA J. R. , ORBUCH M. , STRADER D. B. , NORTON J. A. , JENSEN R. T.
Published: July 2010

A long‐term cure is now possible in more than 30% of selected patients with Zollinger–Ellison syndrome who undergo gastrinoma resection. The need, however, for continued gastric acid antisecretory therapy in these patients remains controversial. The current study was designed to determine whether post‐operative antisecretory therapy is needed in patients who have undergone successful gastrinoma resection and, if so, to attempt to define criteria with which to identify patients who require therapy. Twenty‐eight consecutive patients who had previously undergone curative gastrinoma resection were prospectively studied. When antisecretory therapy was discontinued, 43% (12/28) of these patients developed gastro‐oesophageal reflux, diarrhoea, acid–peptic symptoms or endoscopic evidence of acid‐peptic disease within 2 weeks and were deemed to have failed a trial of antisecretory drug withdrawal. The remaining 57% (16/28) of patients who successfully discontinued antisecretory therapy were followed for a mean time of 31 months after withdrawal of therapy. Analysis of acid output studies pre‐operatively, as well as at the time of drug withdrawal, demonstrated that patients who were unable to discontinue antisecretory therapy exhibited higher pre‐operative maximal acid output values and higher basal acid output values at the time of attempted drug withdrawal than patients who were able to discontinue therapy. Despite these findings, there was significant overlap in acid output values between groups so that it was not possible to define specific acid output criteria for successful drug withdrawal. Pre‐operative clinical characteristics, such as the presence or absence of gastro‐esophageal reflux or acid‐peptic disease, or post‐operative laboratory values, such as the fasting serum gastrin level, did not correlate with the ability to discontinue antisecretory therapy. We conclude that following successful curative gastrinoma resection, 40% of patients still require antisecretory therapy and that both symptom evaluation as well as upper endoscopy should be used to guide attempted drug withdrawal. Although patients who are not able to discontinue therapy have significantly higher acid output measurements than those who are able to discontinue therapy, neither acid output criteria nor any other laboratory or clinical characteristics are able to predict the need for continued antisecretory therapy in these patients.
Short report: the absorption of fluconazole and itraconazole under conditions of low intragastric acidity
Authors: LIM S. G. , SAWYERR A. M. , HUDSON M. , SERCOMBE J. , POUNDER R. E.
Published: July 2010

The study investigated the oral absorption of two anti‐fungal agents, fluconazole and itraconazole, under conditions of low intragastric acidity. Twelve healthy male volunteers received each of 4 dosing regimens: 200 mg itraconazole alone, 200 mg itraconazole and famotidine, 100 mg fluconazole alone, and 100 mg fluconazole and famotidine. Two oral doses of 40 mg famotidine were used to induce hypochlorhydria. Serum drug concentrations were measured (by high pressure liquid chromatography) for 48 h after a single dose of each anti‐fungal agent. When dosed with famotidine, there was a significant 52.9% decrease of the peak intraconazole concentration (P< 0.011), and a significant 51.1% decrease of the 48‐h integrated serum intraconazole concentration (P= 0.005). Famotidine‐induced hypochlorhydria did not affect the absorption of fluconazole.
The mode of action of the aminosalicylates in inflammatory bowel disease
Authors: GREENFIELD S. M. , PUNCHARD N. A. , TEARE J. P. , THOMPSON R. P. H.
Published: July 2010

Sulphasalazine and other 5‐aminosalicylic acid (5‐ASA)‐containing drugs are used in the treatment of acute inflammatory bowel disease and in the maintenance of clinical remission. Despite their use for over 50 years, the mechanism of action of this class of drugs remains uncertain, although a number of possibilities are discussed in this review. It seems likely that the aminosalicylates are important free radical scavengers, can reduce leukotriene production and can inhibit the cellular release of interleukin‐1, all of which are likely to be important in reducing the acute inflammatory response in inflammatory bowel disease, The effects of these drugs on prostaglandin production are more contentious, but it appears that 10‐5to 10‐4M concentrations stimulate production of prostaglandins which may be cytoprotective, while higher doses of these drugs inhibit prostaglandin production. The aminosalicylates may maintain remission in inflammatory bowel disease by preventing leucocyte recruitment into the bowel wall. The drugs inhibit the chemotactic response to leukotriene B4, reduce the synthesis of platelet activating factor and also inhibit leucocyte adhesion molecule upregulation.
Effect of treatment with Liu‐Jun‐Zi‐Tang (TJ‐43) on gastric emptying and gastrointestinal symptoms in dyspeptic patients
Authors: TATSUTA M. , IISHI H.
Published: July 2010

The effects of treatment with the Chinese herbal medicine Liu‐Jun‐Zi‐Tang (TJ‐43) on gastric emptying and gastrointestinal symptoms were investigated in 42 patients with chronic idiopathic dyspepsia. By random allocation, 22 patients received oral treatment with 2.5 g TJ‐43 three times daily, and 20 patients received placebo. Gastric emptying was measured by the acetaminophen absorption method. After 7 days of treatment, gastric emptying was significantly accelerated and gastrointestinal symptoms were significantly reduced in patients treated with TJ‐43. Placebo treatment produced no significant effects. These findings indicate that TJ‐43 had a prokinetic action on gastric emptying and that it was useful in treating chronic dyspepsia.
Short report: treatment of Helicobacter pylori‐associated duodenal ulcer with omeprazole plus antibiotics
Authors: McCARTHY C. J. , COLLINS R. , BEATTIE S. , HAMILTON H. , O'MORAIN C.
Published: July 2010

Omeprazole heals most duodenal ulcers after 4 weeks of treatment but relapse is common. Eradication of Helicobacter pylori is associated with reduced rate of ulcer relapse. This study investigates the effect of omeprazole with antibiotics in H. pylori‐associated duodenal ulceration. Forty‐three patients with endoscopically proven duodenal ulcer and H. pylori entered this study. Treatment consisted of 20 mg omeprazole daily (four weeks) and seven days (first week) treatment with 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. Four weeks after completing the treatment, 81 % (35143) had a healed duodenal ulcer, and 58% (25/43) had H. pylori eradication. In those who healed, at one year 21 remained H. pylori‐negative, 12 had persistent H. pylori infection and 2 had re‐infection. The ulcer relapse rate at one year was 26%: of the 9 who relapsed, 6 had persistent infection, 2 were re‐infected, and only 1 was H. pylori‐negative.

This combination therapy of antibiotics with omeprazole successfully eradicates Helicobacter pylori and has a lower ulcer replase than omeprazole alone.
Short report: effect of sucralfate on angiogenesis in granulation tissue of acetic acid‐induced gastric ulcers in rats
Authors: TSUKAMOTO Y. , TSUCHIDA T. , GOTO H. , HASE S. , ARISAWA T. , NIWA Y.
Published: July 2010

We investigated the effect of sucralfate on angiogenesis in granulation tissue of gastric ulcers induced by acetic acid in rats using the carmine dye method. Intragastric administration of sucralfate at a dose of 500 mg/kg twice daily for 9 days significantly accelerated ulcer healing and significantly increased the extent of angiogenesis in the ulcer base on the tenth day after ulcer induction. As we reported previously, intragastric administration of cimetidine at a dose of 100 mg/kg once daily for 9 days decreased the extent of angiogenesis on the tenth day. However, combination treatment using sucralfate and cimetidine accelerated ulcer healing significantly, without altering the extent of angiogenesis. It is concluded, therefore, that the treatment with sucralfate may be effective in peptic ulcer disease from the standpoint of angiogenesis in the ulcer base.
Efficacy and tolerability of polyethylene glycol‐electrolyte lavage solution with and without simethicone in the preparation of patients with inflammatory bowel disease for colonoscopy
Authors: LAZZARONI M. , PETRILLO M. , DESIDERI S. , PORRO G. BIANCHI
Published: July 2010

This placebo‐controlled study assessed the efficacy and tolerability of polyethylene glycol‐electrolyte lavage solution (PEG‐ELS), with and without simethicone, in the preparation of patients with inflammatory bowel disease for colonoscopy. PEG‐ELS 4 L plus placebo, or PEG‐ELS 4 L plus simethicone 120 mg, was administered according to a randomized double‐blind protocol to 115 patients with ulcerative colitis or Crohn's disease. The parameters assessed were: presence of bubbles, degree of haziness, degree of bowel cleansing and patient acceptance. In the 105 patients completing the study, the efficacy of colonic lavage was found to be essentially comparable for the two preparations, although the addition of simethicone showed a significant reduction in the formation of bubbles. Significantly better results were reported by patients treated with the drug combination regarding reduction of general malaise (P= 0.01) and sleep disturbance (P= 0.01).

The PEG‐ELS solution represents an effective bowel cleansing method which can also be used for patients suffering from inflammatory bowel disease. The addition of simethicone to the traditional formulation is an acceptable development in terms of clinical efficacy and tolerability.
Short report: prospective, randomized trial comparing a single dose sodium phosphate regimen with PEG–electrolyte lavage for colonoscopy preparation
Authors: MARSHALL J. B. , BARTHEL J. S. , KING P. D.
Published: July 2010

We performed a prospective, randomized trial in 52 patients to see how preparation with a single‐dose sodium phosphate solution regimen (Fleet Phospho‐Soda), in which the entire 89 ml dose was given on the evening prior to colonoscopy, compared with conventional polyethylene glycol(PEG)–electrolyte lavage in terms of quality of colon cleansing and ease of patient preparation. Previous trials had utilized a two‐dose sodium phosphate regimen in which one dose was given on the evening prior to colonoscopy and the other on the morning of the procedure. A nurse gave a questionnaire to the patient prior to colonoscopy, assessing how well the preparation was tolerated. The attending gastroenterologist graded the quality of colon cleansing, unaware of how the patient was prepared or tolerated the preparation (1 = excellent, 2 = good, 3 = fair, 4 = unsatisfactory). Both preparations were similarly tolerated. The overall quality of bowel preparation with PEG lavage was significantly better (mean score 1.62) than with the single‐dose sodium phosphate regimen (mean score 2.85) (P= 0.0002). Of 26 patients, 2 (7.7%) undergoing preparation with PEG lavage were judged to have had an unsatisfactory preparation, compared with 8 of 26 patients (30.8%) receiving the sodium phosphate regimen (P = 0.075). We conclude that the single‐dose sodium phosphate regimen is suboptimal for clinical practice and its use cannot be recommended.
Short report: smoking habits and the acquisition of metronidazole resistance in patients with Helicobacter pylori‐related gastritis
Authors: WITTEMAN E. M. , HOPMAN W. P. M. , BECX M. C. J. M. , DE KONING R. W. , TYTGAT G. N. J. , JANSSEN A. J. H. M. , JANSEN J. B. M. J.
Published: July 2010

Thirty‐three dyspeptic patients with colonization of Helicobacter pylorl in the gastric antrum were treated with tripotassium dicitrate bismuthate 120 mg q.d.s. for 28 days and metronidazole 250 mg q.d.s for 10 days starting on day 19. Five weeks after cessation of this treatment regimen H. pylori was eradicated in 23 patients. In 8 of the remaining 10 patients, H. pylori had become resistant to metronidazole. In this study resistance was significantly associated with smoking habits, but not with age, bacterial load, gastritis score or alcohol consumption.
Is there any acid peptic disease that is refractory to proton pump inhibitors ?
Authors: BARDHAN K. D.
Published: July 2010

Non‐healing and delayed healing during acid inhibition treatment depend on the extent to which acid and‘non‐acid’factors are causative in the particular acid peptic disease, and on the effectiveness and duration of acid suppression. Refractoriness (defined arbitrarily) occurs less often with proton pump inhibitors than with H2‐receptor antagonists as the former decrease acid more effectively; H2‐receptor antagonist‐refractory disease usually responds to treatment with proton pump inhibitors. In Rotherham, 5–10% of duodenal ulcer and gastric ulcer patients are refractory (not healed after 3 months of standard‐dose H2‐receptor antagonist). In patients with oesophagitis 15% are refractory to high‐dose H2‐receptor antagonist (for example, 3.2 g cimetidine daily) and 5% to standard‐dose proton pump inhibitors (for example, 20 mg omeprazole daily). In controlled clinical trials of patients with refractory duodenal ulcer, healing at 8 weeks with 40 mg omeprazole o.m. vs. continued standard‐dose H2‐receptor antagonist was 98%vs. 60%; and with 40 mg omeprazole vs. continued high‐dose H2‐receptor antagonist (2 g + 3 g cimetidine, that is, ultra‐refractory disease) was 92%vs. 67%. After healing, in open studies, relapse with maintenance 400‐800 mg cimetidine nocte was 45‐69% at one year, but 0% with 40 mg omeprazole administered for up to 6.5 years. For 53 patients with refractory gastric ulcer, in an open study, healing with omeprazole 40 mg o.m. occurred in 94% at 8 weeks, and none relapsed on long‐term maintenance treatment at this dose. In controlled trials of patients with refractory oesophagitis, healing at 12 weeks with 40 mg omeprazole o.m. vs. high‐dose ranitidine (300 mg b.d.) was 90%vs. 47%, and with maintenance 20 mg omeprazole o.m. vs. 150 mg ranitidine b.d., relapse at 1 year was 32%vs. 88%. In conclusion, acid peptic disease refractory to H2‐receptor antagonists is uncommon and treatment with proton pump inhibitors is effective. Refractoriness to proton pump inhibitors is rare.
Lack of evidence of neurotoxicity following 8 weeks of treatment with tripotassium dicitrato bismuthate
Authors: NWOKOLO C. U. , FITZPATRICK J. D. , PAUL R. , AL R. DY , SMITS B. J. , LOFT D. E.
Published: July 2010

Objective: To search for evidence of subclinical neurotoxicity in patients treated with tripotassium dicitrato bismuthate.

Design: Prospective, controlled, triplicate study using urinary bismuth concentration, magnetic resonance imaging (MRI), nerve conduction studies, visual evoked response and a battery of 10 neuropsychological screening tests.

Setting: Out‐patient clinics, Walsgrave Hospital, Coventry, UK.

Subjects: Fourteen dyspeptic patients; 8 (treatment group) treated with tripotassium dicitrato bismuthate one tablet q.d.s and 6 (control group) treated with ranitidine 150 mg b.d. for 8 weeks.

Main outcome measures: Changes in urinary bismuth, MRI, nerve conduction studies, visual evoked response, and neuropsychological tests performed before, immediately after and 8 weeks after the cessation of treatment.

Results: In the treatment group the median (range) urinary bismuth concentration was 1 (1–12) ng/ml before treatment, increased to 560 (140–1300) immediately after treatment (P < 0.01, Wilcoxon Rank Sum test) and was still significantly elevated (23 (7–53) ng/ml) 8 weeks after the cessation of treatment. In the patient who recorded the highest urinary bismuth, a high intensity signal appeared in the globus pallidus immediately after treatment and was still present (though diminished in intensity) 8 weeks after the cessation of treatment. This isolated MRI finding was not associated with evidence of subclinical neurotoxicity. No changes in the MRI, nerve conduction studies, visual evoked response and neuropsychological tests were observed among the other patients studied.

Conclusions: Bismuth accumulation occurs in patients receiving a conventional course of treatment with tripotassium dicitrato bismuthate but this is not associated with significant changes in the nervous system.
Comparison of pantoprazole and ranitidine in the treatment of acute duodenal ulcer
Authors: JUDMAIER G. , KOELZ H. R. ,   PANTOPRAZOLE‐DUODENAL ULCER‐STUDY GROUP
Published: July 2010

Background:Pantoprazole is a new substituted benzimidazole that blocks the H+/K+‐ATPase in the gastric mucosa and thus inhibits acid secretion.

Methods: Efficacy and tolerability of pantoprazole (40 mg at breakfast) and ranitidine (300 mg at bedtime) in the treatment of uncomplicated acute duodenal ulcer were compared in a double‐blind, randomized multicentre trial.

Results:Of 202 outpatients who entered the study, 185 terminated the treatment without violation of the protocol. After 2 weeks of treatment, healing rates (protocol correct) with pantoprazole and ranitidine were 81 and 53%, respectively (P> 0.001), the corresponding results after 4 weeks were 97 and 83% (P> 0.01). Pantoprazole was more effective with respect to symptom relief. Both treatments were well tolerated.

Conclusion:Pantoprazole 40 mg at breakfast is superior to ranitidine 300 mg at bedtime in the short‐term treatment of acute, uncomplicated duodenal ulcer.
Short report: a comparative study of the interaction between antacid and H2‐receptor antagonists
Authors: SULLIVAN T. J. , REESE J. H. , JAUREGUI L. , MILLER K. , LEVINE L. , BACHMANN K. A.
Published: July 2010

The influence of concomitant antacid administration on the relative bioavailability of the H2‐receptor antagonists cimetidine, famotidine, nizatidine and ranitidine, was investigated in a panel of 21 healthy, adult male volunteers in an eight‐way crossover trial. Administration with antacid reduced the bioavailability of all agents tested. The reduction in area under the serum concentration‐time curve (AUC) was greatest for cimetidine (23%) and ranitidine (26%) and least for nizatidine (12%) and famotidine (19%). Reductions in peak serum concentration (Cmax) followed a similar pattern. The times of peak serum concentrations were not affected by antacid. Comparison of the relative bioavailability among all drugs tested showed no statistically significant differences in the effect of antacid administration on these agents. However, a high degree of intersubject variability was observed.
Short report: zinc sulphate supplementation corrects abnormal erythrocyte membrane long‐chain fatty acid composition in patients with Crohn's disease
Authors: BELLUZZI A. , BRIGNOLA C. , CAMPIERI M. , GIONCHETTI P. , RIZZELLO F. , BOSCHI S. , CUNANNE S. , & M. MIGLIOLI , BARBARA L.
Published: July 2010

Patients with Crohn's disease may become zinc‐deficient and, in such patients, an altered metabolism of radiolabelled long‐chain fatty acids has been reported. We have investigated the possible reversal by zinc supplementation of altered long‐chain fatty acid profiles of red cells in Crohn's disease. Twenty patients with long‐standing Crohn's disease in clinical remission received 200 mg of zinc sulphate daily for 6 weeks. Phospholipid fatty acid profiles of washed red cells were analysed before and after zinc treatment and compared to those of 20 unsupplemented healthy controls.

Plasma zinc levels in Crohn's were 72 ± 8 μg/dL before zinc treatment and increased to 114 ± 10 μg/dl after the therapy. Prior to zinc supplementation, the percentage of palmitic, stearic and oleic acids was significantly higher in Crohn's disease, while linoleic, arachidonic and n‐3 fatty acids were reduced in Crohn's disease compared to healthy controls. Zinc supplementation abolished these pre‐treatment differences in red‐cell long‐chain fatty acid profiles but did not affect plasma fatty acid values. Further studies are needed to clarify whether these fatty acid changes can be related to the clinical course of the disease.
Review article: aspirin and gastrointestinal bleeding
Authors: HAWKEY C.J.
Published: July 2010

Many animal and human studies have shown aspirin to cause gastric mucosal erosions and enhanced spontaneous microbleeding. Chronic use is associated with uncomplicated gastric ulcer (but not clearly with uncomplicated duodenal ulcer) and with presentation with haematemesis and melaena. Sub‐group analysis suggests that the risks of bleeding duodenal ulcer as well as bleeding gastric ulcer (and possibly non‐ulcer bleeding) are increased. These data imply that an anti‐haemostatic as well as an ulcerogenic effect contributes to such presentation and acute data support this proposition. A broken mucosa and inhibition of thromboxane synthesis both appear to be necessary for bleeding to occur. Aspirin enhances the bleeding associated with mucosal biopsy analogous to its prolongation of the skin bleeding time. Anti‐haemostatic properties could account for the apparent increase in presentation with haematemesis and melaena in patients taking low doses of aspirin for cardiovascular prophylaxis. However, acute studies also show aspirin 300 mg to cause a level of mucosal injury which is substantial, though significantly less than with aspirin 600 mg q.d.s. The risk attached to aspirin consumption needs to be kept in perspective. It can be calculated that aspirin use is associated with approximately 700 bleeds per annum in the UK. The relative risk for upper gastrointestinal bleeding is roughly similar to that for non‐aspirin non‐steroidal anti‐inflammatory drugs but those affected are generally younger, in an age group where death from upper gastrointestinal bleeding is very uncommon. In keeping with this and in contrast to non‐aspirin nonsteroidal anti‐inflammatory drugs, no study has shown increased mortality from aspirin‐related upper gastrointestinal complications.
Comparison of acid inhibition by either oral high‐dose ranitidine or omeprazole
Authors: HURLIMANN S. , ABBÜHL B. , INAUEN W. , HALTER F.
Published: July 2010

Background:High‐dose once daily oral omeprazole dosing can inhibit acid secretion almost completely but several days elapse before maximum efficacy is established. The acid inhibitory effect obtained with high doses of a histamine H2‐receptor antagonist is built up rapidly but has the tendency to fade‐the term tolerance’has been applied to characterize this phenomenon.

Methods: To obtain more information on the dynamics of acid inhibition during prolonged dosing, we compared the acid suppressory effects of oral high‐dose omeprazole with high‐dose ranitidine. Twenty‐eight healthy volunteers were randomly assigned to a 2‐week dosing with omeprazole or ranitidine in a double‐blind, double‐dummy, parallel‐group study design. Omeprazole was given as 1 capsule of 40 mg mane and ranitidine as 2 tabs of 150 mg q.d.s. The median 24‐h pH, daytime pH and night‐time pH were measured by ambulatory continuous 24‐h pH metry on days ‐8, ‐6, 1. 2, 7 and 14.

Results: High reproducibility was observed for the two baseline acidity measurements. Ranitidine exerted its peak acid suppressant effect on day 1 of dosing; the degree of acid inhibition faded from day 2 to 7, with no significant change thereafter. The decline in antisecretory activity was more pronounced during the day than the night. In contrast, acid inhibition by omeprazole increased throughout the first week, and antisecretory activity was stable thereafter. Despite the considerable differences in median intragastric pH values at the end of the 14‐day study, plasma gastrin levels were elevated to a similar degree with both medications.

Conclusions: This study confirms the ‘tolerance’phenomenon previously observed with high‐dose histamine H2‐receptor antagonist dosing. The dynamics with which it occurs exclude a typical exaggerated first‐dose response. Prolonged high‐dose histamine H2‐receptor dosing compromises the feedback mechanism regulating gastrin release, whilst this is maintained during dosing with omeprazole.
Rapid healing of gastric ulcers with lansoprazole
Authors: BARDHAN K. D. , AHLBERG J. , HISLOP W. S. , LINDHOLMER C. , LONG R. G. , MORGAN A. G. , SJOSTEDT S. , SMITH P. M. , STIG R. , WORMSLEY K. G. , LANGWORTHY H H. , MOULES I. K.
Published: July 2010

Background: Lansoprazole is a new proton pump inhibitor which powerfully decreases acid secretion.

Methods: We compared the efficacy and short‐term safety of lansoprazole against ranitidine in the healing of gastric ulcer. This was a parallel group, comparative multicentre, prospectively randomized, double‐blind study which included 250 patients with gastric ulcer, 219 of whom had follow‐up endoscopic data.

Results: Both lansoprazole 30 mg and 60 mg daily produced significantly more rapid healing of gastric ulcer than ranitidine 300 mg nightly with healing rates after 4 weeks of 78% (P < 0.05), 84% (P < 0.01) and 61%, respectively. After 8 weeks, the corresponding healing rates were 99%, 97% and 91% (P = 0.08). Symptom relief was similar for all treatment groups, but fewer antacids were used by patients receiving lansoprazole. Sixty‐nine patients experienced 91 adverse events; the incidence, pattern and severity was similar across all three treatment groups.

Conclusions: Lansoprazole 30 mg and 60 mg once daily had similar efficacy. Both were superior to ranitidine 300 mg nocte in healing gastric ulcer. The short‐term safety profile of lansoprazole was similar to ranitidine. These data indicate that lansoprazole should be used at a dose of 30 mg once daily for the treatment of gastric ulcers.
Rolling review–the pathogenesis, diagnosis and management of viral hepatitis
Authors: DUSHEIKO G. M.
Published: July 2010

Five major hepatotrophic viruses have been identified. The pathogenesis, diagnosis and treatment of chronic viral hepatitis continues to be intensely researched. Experimental evidence suggests that HLA restricted virus‐specific T cells play a role in hepatocellular injury in type A hepatitis. The absence of chronic infection indicates the effectiveness of the host immune response to hepatitis A virus (HAV). It is postulated that HAV may rarely trigger an autoimmune chronic hepatitis. Active prophylaxis of hepatitis A is possible.

The elimination of hepatitis B is dependent on the recognition of viral determinants in association with HLA proteins on infected hepatocytes by cytotoxic T cells. The specific epitopes recognized by B and T cells are being mapped. Polymerase chain reaction (PCR) amplification and sequencing of genomic DNA in patients with chronic hepatitis B has indicated that nucleotide substitutions in the genome are not uncommon. Their pathogenicity is being explored. Antiviral therapy for hepatitis B remains difficult. Interferon is effective in a proportion of patients. Thymosin may prove to be more effective immunomodulatory therapy. New nucleoside analogues suppress HBV replication, but the safety of these drugs has been questioned after the appearance of severe liver toxicity with fialuridine.

The data that hepatitis D virus is pathogenic has recently been challenged with the observation that HDV re‐occurs in transplanted liver after engrafting, but without signs of HBV recurrence or evidence of liver damage. Treatment of hepatitis D virus remains difficult.

Several isolates of hepatitis C virus have been cloned, and the sequence divergence of these isolates indicates that there are several major genotypes and component subtypes of this polymorphic virus. Hypervariability of regions of the HCV envelope proteins may be important in persistence of HCV infection and immunopathogenesis. Type C hepatitis has a complex natural history, and several systemic manifestations as well as autoimmune disease have been linked to hepatitis C infection. Alpha interferon is beneficial in 25–30% of patients; certain genotypes may be more sensitive to interferon therapy.

The hepatitis E virus causes acute, and in susceptible populations, fulminant hepatitis. The diagnosis can now be made with tests for anti‐HEV and Polymerase chain reaction.

Other forms of viral hepatitis, particularly those associated with fulminant hepatitis, severe sporadic hepatitis and autoimmune disease are being sought.
Review article: the transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of portal hypertension
Authors: McCORMICK P. A. , DICK R. , BURROUGHS A. K.
Published: July 2010

The transjugular intrahepatic portosystemic shunt (TIPS) is a non‐surgical intrahepatic shunt connecting the hepatic and portal veins. The shunt can be inserted successfully in more than 90% of patients and it effectively decompresses the portal venous circulation. Serious complications, such as intraperitoneal bleeding, occur but they are uncommon. The role of TIPS in the treatment of portal hypertension is currently being evaluated. There are few controlled data available to compare TIPS with established treatments such as drugs, injection sclerotherapy, endoscopic banding or shunt surgery. TIPS has also been used to treat ascites, the Buddxhiari syndrome and cirrhotic hydrothorax. Concerns over the long‐term patency and the true incidence of encephalopathy following TIPS raise doubts about its long‐term efficacy. Controlled trials are required to demonstrate the cost‐effectiveness of TIPS for individual indications before it is widely adopted. TIPS may find its most immediate application in the emergency treatment of active variceal haemorrhage refractory to standard medical and endoscopic therapy, as there is no satisfactory treatment currently available for this high‐risk group. TIPS may also have a role in patients awaiting liver transplantation who bleed from varices. Long‐term patency should not be an issue in this patient group and portal decompression may reduce blood transfusion requirements during transplant surgery.
Effect of decaffeination of coffee or tea on gastro‐oesophageal reflux
Authors: WENDL B. , PFEIFFER A. , PEHL C. , SCHMIDT T. , KAESS H.
Published: July 2010

Background: Coffee and tea are believed to cause gastrooesophageal reflux : however, the effects of these beverages and of their major component, caffeine, have not been quantified. The aim of this study was to evaluate gastro‐oesophageal reflux induced by coffee and tea before and after a decaffeination process, and to compare it with water and water‐containing caffeine.

Methods: Three‐hour ambulatory pH‐metry was performed on 16 healthy volunteers, who received 300 ml of (i) regular coffee, decaffeinated coffee or tap water (n = 16), (ii) normal tea, decaffeinated tea, tap water, or coffee adapted to normal tea in caffeine concentration (n= 6), and (iii) caffeine‐free and caffeine‐containing water (n= 8) together with a standardized breakfast.

Results: Regular coffee induced a significant (P < 0.05) gastro‐oesophageal reflux compared with tap water and normal tea, which were not different from each other. Decaffeination of coffee significantly (P < 0.05) diminished gastro‐oesophageal reflux, whereas decaffeination of tea or addition of caffeine to water had no effect. Coffee adapted to normal tea in caffeine concentration significantly (P < 0.05) increased gastro‐oesophageal reflux.

Conclusions: Coffee, in contrast to tea, increases gastrooesophageal reflux, an effect that is less pronounced after decaffeination. Caffeine does not seem to be responsible for gastro‐oesophageal reflux which must be attributed to other components of coffee.
A dose‐response study of orally administered torsemide in patients with ascites due to cirrhosis
Authors: APPLEFELD J. J. , KASMER R. J. , HAK L. J. , DUKES G. E. , WERMELING D. P. , McCLAIN C. J.
Published: July 2010

Background: This study evaluated the dose‐response relationship of torsemide, the first pyridine‐sulphonylurea loop diuretic, in patients with ascites due to cirrhosis.

Methods: During a 13‐day hospitalization period, 17 patients received single, oral doses of 5 mg, 10 mg, or 20 mg of torsemide or placebo in a randomized, double‐blind, crossover fashion. All the patients received a constant dose of spironolactone concomitantly beginning at least 7 days before the study. Electrolyte excretion and urine volume were measured for 24 h after each dose. Body weight was measured before, and 24 h after each dose.

Results: Torsemide was effective in producing statistically significant, dose‐related increases in urinary sodium and chloride excretion, with little effect on potassium or magnesium excretion. Urine volume increased and body weight decreased in a dose‐related manner.

Conclusion: Torsemide increased sodium excretion substantially in patients with cirrhosis and ascites who were receiving spironolactone.
Alosetron does not affect the visceral perception of gastric distension in healthy subjects
Authors: ZERBIB F. , VARANNES S. BRULEY des , ORIOLA R. C. , McDONALD J. , ISAL J. P. , GALMICHE J. P.
Published: July 2010

Background: The effect of alosetron, a new specific 5‐HT3, receptor antagonist, on the visceral perception in response to gastric distension was assessed in 12 healthy male subjects in a randomized, double‐blind, placebo controlled crossover trial

Methods: Each subject was given orally either alosetron 1 mg b.d. or placebo b.d. for 6 days (wash‐out period 7–28 days). At the end of each dosing period, both isobarometric and isovolumetric gastric distensions were performed using an electronic barostat.

Results: Alosetron did not modify the gastric wall compliance (pressure‐volume relationship). Alosetron had an effect similar to placebo on the visceral perception scores in both isobarometric and isovolumetric distensions. The mean (± SEM) thresholds for abdominal discomfort were, respectively, 16.8 ±0.7 mmHg and 825 ± 61 mL with alosetron, 16.7±0.6 mmHg and 883±45 mL with Placebo (P = NS).

Conclusions: 5‐HT3 receptors do not appear to be involved in the visceral perception of gastric distension in healthy subjects.
Ulceration, fibrosis and diaphragm‐like lesions in the caecum of rats treated with indomethacin
Authors: ANTHONY A. , DHILLON A. P. , SIM R. , NYGARD G. , POUNDER R. E. , WAKEFIELD A. J.
Published: July 2010

Background: Patients on nonsteroidal antiinflammatory drugs can develop curious intestinal fibrotic diaphragms.

Methods: Groups of rats received indomethacin mixed into a powdered diet at 3 mg.kg/day for 6 and 12 weeks and 6 mg. kg/day for up to 6 weeks. In an attempt to reproduce a human dosing regimen, another group of rats, for a total of 30 weeks, received consecutive periods of indomethacin at 3 mg. kg/day for 12 weeks, 4.5 mg.kg/day for 1 week, 6 mg.kg/day for 1 week, control diet for 6 weeks, 4.5 mg.kg/day for 2 weeks and finally, a control diet for a healing period of 8 weeks. Control rats received powdered diet alone. At termination, the small and large intestines were examined macroscopically and histologically.

Results: Indomethacin caused microcytic anaemia, hypoalbuminaemia, small intestinal ulceration, caecal ulceration and inconspicuous raised mucosal lesions in the caecum that histologically showed submucosal fibrosis with disruption and thickening of the apical muscularis mucosae. No control rats showed any abnormality.

Conclusion: These fibrotic lesions of the rat caecum resemble human diaphragms and may arise from healed caecal ulcers.
Scintigraphic assessment of the intragastric distribution and gastric emptying of an encapsulated drug: the effect of feeding and of a proton pump inhibitor
Authors: ATHERTON J. C. , WASHINGTON N. , BRACEWELL M. A. , SUTTON L. J. , GREAVES J. L. , PERKINS A. C. , HAWKEY C. J. , SPILLER R. C.
Published: July 2010

Background: Local delivery of therapeutic agents to the stomach may be a useful strategy in the treatment of Helicobacter pylori infection. We aimed to see whether the intragastric distribution and gastric retention of a therapeutic agent could be improved, either by giving omeprazole or by dosing after a meal.

Methods: Twelve healthy volunteers took part in this double‐blind placebo‐controlled crossover study comparing the effects of omeprazole 20 mg twice daily for 5 days with placebo, and the fasted with the fed state, on the gastric emptying and intragastric distribution of a soluble scintigraphic marker contained in a drug capsule.

Results: Dosing after food profoundly prolonged gastric residence of the drug label, prolonging mean time to 50% emptying (T50) from 0.5 ± 0.1 h in the fasted state to 2.0 ± 0.2 h when given after food. Food also improved intragastric distribution by increasing delivery to the body and fundus. Omeprazole enhanced the effect of food, prolonging T50 to 2.9 ± 0.3 h, but had no effect in fasted subjects.

Conclusions: Dosing after food markedly improves the aspects of local drug delivery to the stomach investigated in this study, and omeprazole enhances this effect. Post‐prandial dosing may, therefore, be useful for improving delivery of some anti‐Helicobacter agents.
Amoxycillin capsules with omeprazole for the eradication of Helicobacter pylori. Assessment of the importance of antibiotic dose timing in relation to meals
Authors: ATHERTON J. C. , HUDSON N. , KIRK G. E. , HAWKEY C. K. , SPILLER R. C.
Published: July 2010

Background: Giving antibiotics after meals prolongs their gastric residence time and improves their intragastric distribution. We aimed to see whether this would result in improved eradication of Helicobacter pylori.

Methods: Eighty patients with H. pylori infection were treated with 40 mg omeprazole in the morning for 28 days and amoxycillin 500 mg q.d.s. for days 15–28. Amoxycillin dosing was randomised to either 1 h before or 10 min after food. Good compliance was pre‐defined as missing less than four doses of amoxycillin or two of omeprazole.

Results: Amoxycillin dosing after meals was shown not to affect H. pylori eradication rate either when results were analysed on an intention‐to‐treat basis [amoxycillin before meals successful in 63% (25/40), after in 65% 26/40)] or for good compliers only [before meals 81% (17/21), after 71% (20/28)]. This excludes, with 95% confidence, a benefit of greater than 18% from dosing before, or 23% from dosing after meals. Good compliance, however, was shown to be important, with H. pylori eradication in 76% (37/49) of good compliers compared with 48%(11/23) of others completing the protocol (P < 0.05).

Conclusions: The timing of antibiotic administration in relation to meals is not important in the treatment of H. pylori infection with this regimen of amoxycillin capsules and omeprazole. Good compliance, is however, an important determinant of treatment success.
Low dose aspirin: selective inhibition of rectal dialysis thromboxane B2 in healthy volunteers
Authors: COLE A. T. , FILIPOWICZ B. , HYMAN‐TAYLOR P. , HAWKEY C. J.
Published: July 2010

Aim: To investigate the degree and selectivity of rectal thromboxane inhibition by low dose aspirin and there by investigate the contribution of platelet thromboxane to rectal thromboxane.

Methods: The study was a randomized double‐blind placebo controlled crossover study. Twelve healthy volunteers were studied, each over four separate study periods with two weeks wash‐out between each period. Changes in levels of thromboxane (TX) B2, prostaglandin (PG) E2 and leukotriene (LT) B2 in rectal dialysates were measured in response to 5 days oral low dose aspirin therapy in one of three once‐daily formulations (plain 75 mg, plain 300 mg or enteric coated 300 mg), and compared to placebo. For each study period, rectal dialysates (4 h duration) were obtained at baseline and twice more after 5 days of aspirin or placebo therapy. Dialysate levels of thromboxane B2, leukotriene B4, prostaglandin E2, and serum thromboxane B2 were measured by radioimmunoassay.

Results: Dialysate thromboxane B, levels were consistently inhibited by low dose aspirin (overall results of all formulations, 75 to 300 mg daily) from 1.06 ng/ml (geometric mean, 95 % CI:0.79–1.43 ng/ml) on placebo, by 29% (95% CI: 11–40%) to 0.75 ng/ml(0.56–1.01 ng/ml) (P= 0.046) on aspirin. In the absence of aspirin the level of prostaglandin E, was 1.47 ng/ml (0.97–2.23 ng/ml) and in the presence of aspirin was not significantly changed. The dialysate level of leultotriene B, was 0.45 ng/ml(0.34–0.61 ng/ml) in the absence of aspirin and there was no significant change on low dose aspirin. Serum thromboxane was inhibited by 80% to 20% of placebo values by plain aspirin 75 mg, by 95 % by plain aspirin 300 mg, and by 82 % by enteric coated aspirin 300 mg, respectively (P < 0.01). These results show that 29 % of the rectal thromboxane, but none of the rectal prostaglandin E2 or leukotriene B4, is inhibited by low dose aspirin. We infer that 34% of the rectal thromboxane B2 is platelet‐derived in our volunteers.

Conclusion: Low dose aspirin will selectively inhibit a proportion of rectal thromboxane and may have prophylactic therapeutic potential in inflammatory bowel disease.