bluuebunny/crossref_metadata_2025 huggingface dataset:
Short report: clarithromycin, an alternative to metronidazole in the triple therapy of Helicobacter pylori infection
Authors: THIJS J. C. , VAN ZWET A. A. , MOOLENAAR W. , OOM J. A. J. , DE KORTE H. , RUNHAAR E. A.
Published: July 2010

Background: Triple therapy for Helicobacter pylori using metronidazole is less effective in patients with a metronidazole resistant strain. Moreover, metronidazole is responsible for many side‐effects. This open study examined the efficacy and side‐effects of a triple treatment regimen substituting clarithromycin for metronidazole.

Methods: 36 patients with a H. pylori infection, proven by culture, were treated with tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 250 mg q.d.s. and clarithromycin 250 mg q.d.s. for 10 days.

Eradication was defined as a negative culture and histological examination of antral biopsy specimens, taken at least 6 weeks after completion of the treatment.

Results: Eradication was achieved in 26 patients (72%). The treatment was well tolerated with only 4 (11 %) of the patients having significant side‐effects.

Conclusion: Triple therapy with clarithromycin seems to be less effective than standard triple treatment when the prevalence of metronidazole resistance is low. It is suggested, however, that this combination could be a valuable alternative in areas with a high prevalence of metronidazole resistance.
Short report: long‐term management of peptic ulcer disease with ranitidine in Germany
Authors: SIMON B. , SCHÜTZ E. , MÜLLER P. , DIXON J. S.
Published: July 2010

One hundred and twenty‐five patients with duodenal ulcer disease were given continuous ranitidine therapy after initial acute healing. Cumulative remission rates indicated that 95 % of patients were ulcer‐free after 1 year, 89% at 2 years, 81% at 3 years, 70% at 4 years and 60% at 5 and 6 years. Nine patients had a second recurrence after healing of the first. No patient developed an ulcer complication. These results support the view that long‐term continuous ranitidine therapy prevents ulcer recurrence and complications.
Comparative effects of H2‐receptor antagonists on subjective and objective assessments of sleep
Authors: ORR W. C. , DUKE J. C. , IMES N. K. , MELLOW M. H.
Published: July 2010

Background:Clinically, it is common for patients to experience drowsiness in association with consumption of H2receptor antagonists. Reported side‐effects with H2‐receptor antagonists include insomnia and somnolence. The present study was designed to assess and compare the effects of three H2‐receptor antagonists (cimetidine, famotidine, and ranitidine) on nocturnal and daytime sleepiness.

Methods: This is a double‐blind crossover study on 12 normal volunteers. Subjects were studied under conditions of placebo, cimetidine (400 mg b.d.), famotidine (20 mg b.d.), and ranitidine (150 mg b.d.) for one week. Sleep was assessed at the end of each one‐week interval via polysomnographic evaluation conducted on nights 6 and 7 of drug administration. On the day between the two nights in the sleep laboratory, a multiple sleep latency test was conducted.

Results: The results revealed a significant reduction in the sleep onset latency with famotidine administration, but since there were no effects of any of the medications in the multiple sleep latency test, this finding is of dubious clinical significance. Cimetidine revealed a small increase in subjective estimates of sleepiness. No effects on sleep‐related respiratory parameters were noted.

Conclusions: This study demonstrates the lack of effect of peripheral administration of H2‐receptor antagonists on sleep stages, while subjective or objective assessment of daytime alertness revealed small effects of famotidine and cimetidine.
Short report: the effect of misoprostol on the anaemia of NSAID enteropathy
Authors: MORRIS A. J. , MURRAY L. , STURROCK R. D. , MADHOK R. , CAPELL H. A. , MACKENZIE J. F.
Published: July 2010

Background: Small bowel ulceration is an increasingly recognised complication of therapy with non‐steroidal anti‐inflammatory drugs (NSAID). The ulceration is a potent site of blood loss contributing to unexplained iron deficiency anaemia in patients with arthritis. No drug is currently available to treat NSAID small bowel ulcers.

Methods: We have retrospectively examined the effect of therapy with the prostaglandin El analogue misoprostol on the anaemia of patients with enteroscopically proven NSAID small bowel enteropathy.

Results: All of the patients had proven iron deficiency anaemia. Eleven patients received misoprostol and ten received no treatment. Haemoglobin in the misoprostol‐treated group rose significantly from median (range) 9.1 (6.2–10.6) g/dL (95% confidence intervals 8.76, 10.13) to 10.6 (6.5–16.8) g/dL (95% confidence intervals 10.06, 11.82); P= 0.004). Those patients who did not receive misoprostol had no significant change in their haemoglobin: 9.1 (7.5–10.6) g/dL to 8.1 (5.6–14.7) g/dL (P= N.S.).

Conclusion: Misoprostol therapy was associated with an improvement in the anaemia in patients with proven NSAID enteropathy.
Review article: orthograde gut lavage for colonoscopy
Authors: BERRY M. A. , DiPALMA J. A.
Published: July 2010

Most colon cleansing regimens for surgical and diagnostic procedures such as colonoscopy are modifications of older barium enema X‐ray preparations which have evolved in gastrointestinal laboratories influenced by empiric experience. Recent formal study allows for careful comparison of gut lavage, diet and cathartic, and oral sodium phosphate preparations. This review will evaluate oral lavage solutions and address their safety, tolerance and efficacy. Administration options are discussed as well as other diet and cathartic methods previously referred to as ‘standard preps’.
A dose‐ranging study of ranitidine and its effect on intragastric and intra‐oesophageal acidity in subjects with gastro‐oesophageal reflux disease
Authors: THOMSON A. B. R. , BABIUK L. , KIRDEIKIS P. , ZUK L. , MARRIAGE B. , BOWES K.
Published: July 2010

Methods: This randomized, double‐blind, single‐centre, crossover study was designed to assess the effects of three regimens of ranitidine (150 mg b.d., 300 mg b.d. and 300 mg q.d.s.) and placebo on intra‐oesophageal and intragastric pH in subjects with gastro‐oesophageal reflux disease (GERD). Twenty‐six subjects were screened, and 9 were evaluable by the admission criteria. These 9 subjects received each of the regimens for 72 h, and a wash‐out period of at least 48 h followed each dosing period. Standard meals and beverages were provided.

Results: With increasing doses of ranitidine, 24‐h intragastric mean H+ and integrated H+ fell, and the percentage of the time the pH was equal to or greater than 4 (% time pH ≥ 4) rose; the minimum effective dose for these effects was ranitidine 300 mg daily. With increasing doses of ranitidine there was also a progressive decline in mean 24‐h intra‐oesophageal H+ and integrated H+, and increasing % time pH ≥ 4. The minimal effective dose was 300 mg daily for intra‐oesophageal mean H+ and integrated H+, and 600 mg for % time pH ≥ 4. The minimal effective dose to decrease the number of reflex episodes was 1200 mg ranitidine. For the daytime upright position, a dose effect of increasing ranitidine was also seen, with minimal effective ranitidine doses of 300 mg for a decrease in mean H+, and 1200 mg for % time pH ≥ 4. Conclusion: If these higher doses of ranitidine are confirmed to be more effective than the standard 150 mg b.d. regimen for the treatment of patients with gastro‐oesophageal reflux disease, then the mechanism of this action probably relates to the lower exposure of the oesophageal mucosa to acid.
Steroid treatment in active Crohn's disease: a comparison between two regimens of different duration
Authors: BRICNOLA C. , DE SIMONE G. , BELLOLI C. , IANNONE P. , BELLUZZI A. , GIONCHETTI P. , CAMPIERI M. , BARBARA L.
Published: July 2010

Background: Steroids are highly effective in active Crohn's disease; clinical relapse following steroid withdrawal, however, is frequent. We used two steroid regimens of different duration in order to compare their efficacy in inducing and maintaining clinical remission. Methods: Seventy patients with active Crohn's disease were treated with methylprednisolone 40 mg/day i.m. for 3 weeks and then with two different regimens of tapering dosage: one for a further 4 weeks and another for a further 12 weeks.

Results: Steroid therapy induced remission within 3 weeks in 91 % of the whole group of patients: at the end of each protocol remission rates were 85% of patients in the group treated for the shorter period and 87% of those treated for the longer period (difference 2%. CI = ‐ 14 to 18, P = NS); remission rates within 6 months after stopping steroids were 53% and 37% respectively (difference 16%, CI = ‐9 to 41, P = NS). Conclusions: No significant differences were found between the two regimens. Multiple courses of steroid treatment in the previous 3 years and a short time interval following previous steroid treatment seem to be risk factors for relapse.
Bran supplementation in the treatment of irritable bowel sgndrome
Authors: SNOOK J. , SHEPHERD H. A.
Published: July 2010

Background: Irritable bowel syndrome remains the commonest reason for referral to a gastroenterology clinic. Patients with irritable bowel syndrome are frequently advised to increase their intake of bran fibre, despite inconclusive experimental evidence of benefit.

Methods: The effect of dietary supplementation with a bolus of bran fibre (12 g/day) was studied in a block‐randomized, placebo‐controlled, crossover study of 80 patients with irritable bowel syndrome referred to a District General Hospital outpatient clinic. Comparison of the benefits of bran and placebo was based upon personal assessment of individual and overall symptom profiles, determined from a simple daily symptom score and post‐treatment interview.

Results: Overall symptomatic improvement was reported with bran by 52% and with placebo by 54% of patients. Bran supplementation was no more effective than placebo in improving individual symptoms of irritable bowel syndrome, and for wind‐related symptoms it was significantly less effective (P < 0.001).

Conclusion: Dietary supplementation with bran is of no value in the treatment of patients with irritable bowel syndrome referred to a hospital clinic.
Effects of pantoprazole on endocrine function in healthy male volunteers
Authors: DAMMANN H. G. , BETHKE Th. , BURKHARDT F. , WOLF N. , KHALIL H. , LUEHMANN R.
Published: July 2010

Method:In a randomized, double‐blind, two‐period crossover study, pantoprazole 40 mg or placebo were given orally to 12 male volunteers for 2 weeks each. There was a wash‐out period of at least 1 week between the two treatment periods. The effects of pantoprazole or placebo on cortisol and testosterone (primary criteria), and tri‐iodothyronine, thyroxine, thyroid‐stimulating hormone, thyronine‐binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle‐stimulating hormone, luteotrophic hormone, prolactin and somatotrophic hormone were compared. In addition, intragastric 24‐h pH, 24‐h H+‐activity, and volume of nocturnal gastric juice were determined by gastric aspiration technique.

Results:Pantoprazole did not influence plasma levels of testosterone, circadian cortisol concentrations or plasma cortisol levels after exogenous adrenocorticotropic hormone stimulation, as compared to placebo (P> 0.05, Koch's test). Furthermore, there were no clinically relevant changes with any of the other endocrine parameters. Pantoprazole significantly increased the median 24‐h pH (group median 4.3 vs. 1.8;P< 0.001) and decreased 24‐h H+‐activity (4.0 vs. 22.6 mmol/L;P< 0.001). The volume of nocturnal gastric juice did not significantly differ between the two treatments. Pantoprazole was well tolerated and the frequency of adverse events was similar to placebo. No drug‐related changes in laboratory values were observed.

Conclusion:Pantoprazole did not influence endocrine function in healthy male volunteers during short‐term treatment.
Studies of water movement across the gut using oral rehydration solutions in a rat perfusion model
Authors: PILLAI G. V. , BRUETON M. J. , BURSTON D. , SANDHU B. K.
Published: July 2010

Aim: To measure water influx and efflux, as well as net water, sodium and potassium absorption from a range of oral rehydration solutions (ORS) in which the glucose content had been partially replaced with the amino acid leucine or with food supplements.

Methods: A series of in vivo steady‐state perfusion studies in normal rat intestine. The oral rehydration solutions contained 60 or 90 mmol/L of sodium. The reference solution used was the World Health Organization (WHO) formula.

Results: There was a significant negative correlation between the oral rehydration solution osmolality and net water absorption (r=–0.722, P < 0.05). The highest net water absorption occurred using comminuted chicken supplemented oral rehydration solution containing 60 mmol/L sodium (P < 0.001). This oral rehydration solution also showed a significant increase in the rate of influx of water (P < 0.05) in comparison with the WHO formula containing 60 mmol/L sodium.

Conclusion: This work provides further evidence that food‐based oral rehydration solutions, including non‐vegetable sources, may have a useful role to play in the management of patients with acute diarrhoea.
Comparative assessment of phenolphthalein and phenolphthalein glucuronide: is phenolphthalein glucuronide a better laxative?
Authors: ANAND B. S. , TORRES E. , OPERKUN A. , GRAHAM D. Y.
Published: July 2010

Background: Phenolphthalein is widely used as a safe and effective laxative. After oral administration, phenolphthalein is absorbed in the small bowel and is conjugated in the liver to phenolphthalein glucuronide which passes into the colon where it is deconjugated and the active compound, phenolphthalein, is released. Since phenolphthalein glucuronide does not undergo enterohepatic circulation it should theoretically have a more rapid onset of action and a lower threshold dose for taxation. The present study was designed to examine this issue.

Methods: Ten normal healthy subjects volunteered for the study. All subjects were administered placebo, phenolphthalein (at doses of 15, 30, 45, 60, 75 and 90 mg) or phenolphthalein glucuronide (at equivalent doses of 24, 48, 72, 96, 120 and 144 mg) in a random order. Stool weight, the frequency and consistency of stools, and the development of symptoms were recorded at 12‐h intervals for 84 h.

Results: There was a significant increase in the mean stool weight obtained within the first 24 h of administration of a 30 mg dose of phenolphthalein and its glucuronide equivalent compared to the values obtained with placebo. A further increase in the dose did not improve the therapeutic response. There was no difference between phenolphthalein and phenolphthalein glucuronide with respect to the rapidity of action, the threshold dose, effectiveness of taxation, or the frequency of adverse effects.

Conclusions: The therapeutic response and side effect profile of the different doses favoured 30 mg phenolphthalein as the optimum laxative dose. Although theoretically superior, phenolphthalein glucuronide was not found to be a more effective laxative compared to phenolphthalein in normal subjects.
Influence of octreotide on the gastric emptying of solids and liquids in normal healthy subjects
Authors: MAES B. D. , GHOOS Y. F. , GEYPENS B. J. , HIELE M. I. , RUTGEERTS P. J.
Published: July 2010

Background: The effects of octreotide on small intestinal and gall‐bladder motility are well established. However, the influence of octreotide on the gastric emptying rate of both solids and liquids in normal healthy volunteers has never been studied.

Methods: In nine healthy subjects, the gastric emptying rate of liquids and solids was studied in basal condition and 30 min after subcutaneous administration of 50 μg of octreotide, using the combined 14C‐octanoic acid/13C‐glycine breath test. To determine if the results were entirely due to alterations in gastric emptying, 14/13CO2 excretion rates of intraduodenally administered 14C‐octanoic acid and 13C‐glycine were measured in basal condition and after subcutaneous injection of octreotide.

Results: After subcutaneous injection of octreotide, the gastric emptying rate of solids was decreased in all but one subject, while the gastric emptying rate of fluids was decreased in all subjects. Nevertheless, 14/13CO2 excretion rates in the breath after intraduodenally administered 14C‐octanoic acid and 13C‐glycine, were similar in basal condition and after subcutaneous injection of octreotide.

Conclusions: Subcutaneous injection of a single physiological dose of octreotide induces a marked delay in the gastric emptying of solids and liquids in young healthy volunteers. The combined 14C‐octanoic acid/13C‐glycine breath test is very well suited to demonstrate this effect, since the absorption and metabolism of octanoic acid and glycine remains unaltered after administration of octreotide.
Pantoprazole versus omeprazole in the treatment of acute gastric ulcers
Authors: WITZEL L. , GÜTZ† H. , HÜTTEMANN W. , SCHEPP W.
Published: July 2010

Background: Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+,K+‐ATPase.

Methods: The proton pump inhibitors pantoprazole and omeprazole were compared in a randomized, doubleblind study in 219 patients with benign gastric ulcers. Patients received either pantoprazole 40 mg (n= 146) or omeprazole 20 mg (n= 73), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the ulcer had not healed.

Results: After 4 weeks, complete ulcer healing was seen in 88% of protocol‐correct patients given pantoprazole and in 77% given omeprazole (between‐group differenceP< 0.05). At 8 weeks, the corresponding values were 97% and 96% (not significant). In the comparative intention‐to‐treat analysis there were no statistical differences between the treatment groups. Among the patients who had ulcer pain prior to treatment, 79% of the pantoprazole group and 68% of the omeprazole group were pain‐free after 2 weeks, and after 4 weeks 88% and 81%, respectively (not significant). Pronounced improvement in the other gastrointestinal symptoms was seen in both groups. Only 10% of patients in each group reported adverse events. There were moderate increases in fasting serum gastrin levels with both treatments at 4 and 8 weeks.

Conclusion: Pantoprazole, 40 mg once daily in the morning, is a highly effective, well tolerated treatment for acute, benign gastric ulcer. Pantoprazole and omeprazole were equally safe in the therapy of gastric ulcer.
A comparison of lansoprazole and ranitidine in the treatment of erosive oesophagitis
Authors: ROBINSON M. , SAHBA B. , AVNER D. , JHALA N. , GRESKI‐ROSE P. A. , JENNINGS D. E.
Published: July 2010

Background: Lansoprazole is a new proton pump inhibitor which produces prolonged decrease of gastric acidity. The aim of this study was to compare lansoprazole to a standard dose of ranitidine in the treatment of patients with reflux oesophagitis.

Methods: Two hundred and forty‐seven patients with erosive oesophagitis were randomly assigned to 8 weeks of treatment with either 30 mg lansoprazole once daily or 150 mg ranitidine twice daily.

Results: Two hundred and forty‐two patients were included in the analysis. Lansoprazole (30 mg) daily, healed oesophagitis in 92.1% of patients after 8 weeks of treatment. This was significantly superior to 150 mg ranitidine b.d.s. which healed oesophagitis in 69.9% of patients (P < 0.001). Relief of reflux symptoms was superior with lansoprazole to that with ranitidine. Both lansoprazole and ranitidine were well tolerated with no serious drug‐related adverse events noted.

Conclusion: Lansoprazole, 30 mg once daily, is highly effective and safe in the short‐term treatment of erosive oesophagitis.
Eflect of lactose, lactulose and bisacodyl on gastrointestinal transit studied by metal detector
Authors: EWE K. , UEBERSCHAER B. , PRESS A. G. , KURRECK C. , KLUMP M.
Published: July 2010

Aim and methods: To study the effect of 45 g lactose, 30 g lactulose and 10 mg bisacodyl on gastrointestinal transit in 30 healthy volunteers by metal detector and Hinton marker method. The first set of measurements were performed under standard conditions. In a second stage, transit was slowed to twice the original value by loperamide to simulate constipation conditions.

Results: Bisacodyl drastically accelerated small and large intestinal transit. Colonic transit was shortened to 23 % and to 31% of control values, without and with loperamide. Bisacodyl increased stool weight and decreased stool consistency in all persons. Lactulose marginally shortened small intestinal transit (P= 0.08) but significantly increased stool weight and decreased stool consistency. The accelerating effect of lactose on small intestinal transit was abolished by loperamide. Lactose did not influence colonic transit, stool weight or stool consistency. Results of metal detector and Hinton marker method corresponded well (r=0.75), the metal detector method measuring slightly shorter transit times than the Hinton marker method.

Conclusions: With the dose chosen in this trial, lactose did not have any laxative effect in lactose tolerant persons. Laxative effect was mild with lactulose and most pronounced with bisacodyl.
Tolerability of interferon alpha‐2b, a possible new treatment of active Crohn's disease
Authors: DAVIDSEN B. , MUNKHOLM P. , SCHLICHTING P. , NIELSEN O. H. , KRARUP H. , BONNEVIE‐NIELSEN V.
Published: July 2010

Background and aims: Due to the need for new principles for the treatment of Crohn's disease and due to the documented immunomodulatory effects of interferon alpha, the tolerability and effect(s) of interferon alpha‐2b (Introna) in active Crohn's disease were examined in a pilot study.

Methods: Five patients with active Crohn's disease (activity index (CDAI) scores of 235–517), were treated with interferon alpha‐2b for 12 weeks.

Results: All patients tolerated the treatment, but developed influenza‐like symptoms, which were fully controlled by paracetamol. Two patients obtained partial remission with a decline in activity index scores of 39% and 50%. The activity of 2′, 5′‐oligoadenylate synthetase, which together with two other interferon‐induced proteins, neopterin and β2‐microglobulin were increased during treatment, indicated clearly an in vivo uptake of interferon. Sedimentation rate, C‐reactive protein, orosomucoid, albumin, specific inflammatory markers: soluble interleukin‐2 α‐receptors (sIL‐2R) and intercellular adhesion molecule‐1 (ICAM‐1) did not show any changes before or after treatment.

Conclusion: Future multicentre investigations are required to evaluate the clinical effect of interferon alpha‐2b treatment in active Crohn's disease.
Lansoprazole versus ranitidine for the treatment of reflux oesophagitis
Authors: BARDHAN K. D. , HAWKEY C. J. , LONG R. G. , MORGAN A. G. , WORMSLEY K. G. , MOULES I. K. , BROCKLEBANK D.
Published: July 2010

Background: Lansoprazole is a H+, K+‐ATPase (proton pump) inhibitor with an anti‐secretory action and is therefore potentially useful in the treatment of gastro‐oesophageal reflux.

Methods: This study was conducted to determine the efficacy and short‐term safety of lansoprazole at doses of 30 mg or 60 mg once daily, compared with ranitidine 150 mg twice daily, in the treatment of patients with reflux oesophagitis. This was a double‐blind, stratified, randomized, comparative, parallel group study conducted in five centres in the UK. A total of 229 patients (155 men) aged 18–79 years with endoscopically‐confirmed oesophagitis were randomized to receive lansoprazole 30 mg p.o. daily, lansoprazole 60 mg p.o. daily, or ranitidine 150 mg p.o. b.d. Efficacy was assessed by endoscopic examination at 4 weeks and 8 weeks, together with symptom relief and antacid usage.

Results: Lansoprazole 30 mg and 60 mg were superior at 4 and 8 weeks (P < 0.01) to ranitidine in healing reflux oesophagitis: respective healing rates being 84%, 72% and 39% after 4 weeks and 92%, 91% and 53% after 8 weeks. Relief of heartburn with lansoprazole 30 mg and 60 mg was superior to that achieved with ranitidine at both week 4 (P < 0.01) and week 8 (P < 0.02).

Sixty‐four patients experienced a total of 85 adverse events, one‐third of which were considered drug‐related. The incidence and severity were similar in the three groups.

Conclusion: Lansoprazole 30 mg and 60 mg once daily are more effective than ranitidine 150 mg twice daily in the short‐term treatment of reflux oesophagitis.
Rectal aminosalicylate therapy for distal ulcerative colitis: a meta‐analysis
Authors: MARSHALL J. K. , IRVINE E. J.
Published: July 2010

Background: To summarize and quantify the evidence supporting rectal 5‐ or 4‐aminosalicylate (ASA) therapies for disease exacerbation or remission maintenance in distal ulcerative colitis, we performed a meta‐analysis.

Methods: All randomized, double‐blind controlled trials involving aminosalicylate therapy were retrieved from a MEDLINE search, review articles on ulcerative colitis therapy or their bibliographies. Of 55 studies retrieved, 19 met the inclusion criteria. Appraisal and data extraction were performed by two observers and scoring disagreements were resolved by consensus.

Results: Eleven trials tested 5‐ASA and three tested 4‐ASA in active ulcerative colitis. 5‐ASA was superior to placebo for inducing remission or symptomatic improvement in active ulcerative colitis with a pooled odds ratio of 7.36 (95% Confidence interval (CI): 4.72–11.47). In four trials the pooled odds ratio for endoscopic improvement was 10.04 (95 % CI: 5.72–17.61) and for histological improvement 10.31 (95% CI: 5.85–18.18). Studies evaluating 4–ASA suggest a benefit similar to prednisolone in treating active disease. Five trials assessed remission maintenance with 5‐ASA, and when compared to placebo gave a pooled odds ratio of 16.22 (95% CI: 4.71–55.92). No dose‐response relationship was observed. ASA compounds were not therapeutically superior to other treatments.

Conclusions: We conclude that rectal 5‐ASA is effective therapy for active distal ulcerative colitis. More trials are needed to assess 4‐ASA, dose‐response effects and the ideal regimen for remission maintenance.
Effects of FK506 on an experimental model of colitis in rats
Authors: HOSHINO H. , GOTO H. , SUGIYAMA S. , HAYAKAWA T. , OZAWA T.
Published: July 2010

Aim: To assess the effects of FK506, a newly developed immunosuppressant, on experimental colitis in rats.

Methods: Experimental colitis was induced by a single colonic instillation of hapten 2,4,6‐trinitrobenzene sulphonic acid (TNB) in anaesthetized rats. Rats received 30 mg TNB dissolved in 0.25 mL of 50% ethanol, and were sacrificed on day 5 following 4 days dosing with FK506 (0.25, 0.5, 1.0, 2.0 mg/kg, s.c.) or vehicle. Mucosal prostanoid concentrations were determined using high performance liquid chromotography. Tissue myeloperoxidase activities were measured. The effects of FK506 on superoxide radical formation by neutrophils in both rats and humans were also estimated in vitro.

Results: Administration of FK506 significantly reduced the colonic damage in a dose‐dependent manner. Activities of myeloperoxidase and concentrations of 6‐keto‐prostaglandin Fl1α (6‐keto‐PGF1α, PGF2α and PGE2 in colonic tissue increased significantly following induction of experimental colitis, however, FK506 did not affect these changes. FK506 reduced stimulant‐induced superoxide radical formation by neutrophils in rats and humans.

Conclusion: FK506 decreased superoxide radical generation by neutrophils, which might contribute to the lessening of colonic damage in this model.
Octreotide treatment of carcinoid syndrome: analysis of published dose‐titration data
Authors: HARRIS A. G. , REDFERN J. S.
Published: July 2010

Background: Octreotide has proven therapeutically effective in carcinoid syndrome, but the rarity of carcinoid tumors has hampered detailed dose‐ranging studies. This study analysed published dose‐titration data on octreotide use in carcinoid patients to (a) investigate the relation between octreotide dose and efficacy and (b) establish octreotide dosing recommendations for maximum therapeutic benefit. Method: An exhaustive, computer‐assisted literature search for published articles employing octreotide to manage patients with carcinoid syndrome was performed using several databases. The relation between octreotide dose and efficacy in decreasing urinary 5‐hydroxyindoleacetic acid (5‐HIAA) levels, flushing and diarrhoea was analysed for seven dose ranges by pooling data from selected articles.

Results: Analysis of data compiled from 62 published studies revealed that maximum effective therapeutic doses of octreotide effectively controlled symptoms in up to 93 % of patients, and that increasing the dose of octreotide is associated with increased benefit with respect to control of flushing, diarrhoea and 5‐HIAA levels.

Conclusions: We recommend starting octreotide therapy at 100 μg subcutaneously t.d.s. in patients with mild/moderate, non‐life‐threatening carcinoid syndrome. Since therapeutic response to octreotide varies markedly among patients, we recommend titrating the octreotide dose in increments of 50–100 μg every 8 h until adequate symptom control is achieved.
Double‐blind, randomized trial of roxatidine 150 mg in the early evening versus bedtime administration in the short‐term treatment of duodenal ulcer
Authors: LAZZARONI M. , CANALI A. , PORRO G. BIANCHI
Published: July 2010

Aim: To compare the efficacy and tolerability of early evening (19.00–21.00 hours) vs. bedtime (22.00–00.00 hours) oral administration of roxatidine 150 mg in the short‐term treatment of active duodenal ulcer.

Methods: The trial was randomized, double‐blind and double‐dummy, with parallel groups. A total of 276 patients were recruited and randomly assigned either to roxatidine in the early evening (n= 139) or roxatidine at bedtime (n= 137).

Results: After 4 weeks, 78% of patients receiving roxatidine in the early evening and 74% of those treated at bedtime had achieved complete healing, as determined by per‐protocol analysis. With intention‐to‐treat analysis the healing rates were 70.5% and 70.8%, respectively. After 8 weeks the healing rates in the early evening and bedtime treatment groups were 92% and 95% (per‐protocol analysis) and 78% and 84% (intention‐to‐treat analysis). Both treatments proved effective in reducing the frequency and severity of daytime and nocturnal epigastric pain, as well as other ulcer‐related symptoms.

Conclusions: This study confirmed the healing and analgesic properties of roxatidine in duodenal ulcer disease. Early evening or bedtime dosing with roxatidine 150 mg resulted in similar 4‐ to 8‐week rates of duodenal ulcer healing.
Effect of omeprazole and feeding on plasma gastrin in patients with achlorhydria
Authors: BANERJEE S. , ARDILL J. E. S. , BEATTIE A. D. , McCOLL K. E. L.
Published: July 2010

Background: The mechanism of hypergastrinaemia during omeprazole therapy is unclear, but is generally assumed to be entirely a consequence of acid suppression. However, direct stimulation of G cells by omeprazole could also be a factor. In order to further investigate the mechanism of omeprazole‐induced hypergastrinaemia, we have studied the effects of the drug on plasma gastrin in patients with achlorhydria, in whom altered acid secretion cannot play a role. Methods: We estimated fasting and peptone meal stimulated plasma gastrin in nine patients (seven female) with pernicious anaemia and achlorhydria, before and on the final day of 4 weeks’dosing with omeprazole 40 mg daily.

Results: Despite the high fasting gastrin concentrations, the peptone meal produced a further elevation in plasma gastrin concentrations, median gastrin concentrations rising from 1500 ng/L (range 225–10875 ng/L) to 3750 ng/L (range 585–15600 ng/L) post‐prandially (P = 0.004). The median post‐prandial rise in plasma gastrin at this initial visit was 44% (3–260%), and the median time interval until plasma gastrin concentrations returned to fasting levels was 120 min (range 10‐ > 150 min). There was a significant negative correlation between fasting plasma gastrin concentrations and the percentage increase in plasma gastrin levels in response to meal stimulation (Spearman correlation coefficient ‐0.79, P= 0.01). Fasting plasma gastrin concentrations were similar pre‐omeprazole (median 1950 ng/L, range 240–16500 ng/L) and postomeprazole (median 1500 ng/L, range 315–7650 ng/L). Likewise, peak plasma gastrin concentrations were also similar pre‐omeprazole (median 2700 ng/L, range 585–16500 ng/L) and post omeprazole (median 3420 ng/L, range 720–11250 ng/L).

Conclusions: (i) The hyperplastic G cell mass in patients with pernicious anaemia can be further stimulated by a peptone meal, which causes a prolonged rise in plasma gastrin concentrations. (ii) There is a negative correlation between fasting plasma gastrin concentrations and the percentage increase in plasma gastrin levels in response to meal stimulation. (iii) Omeprazole has no effect on plasma gastrin in achlorhydric patients, which is consistent with its hypergastrinaemic effect being entirely secondary to acid inhibition.
A comparison of three doses of lansoprazole (15, 30 and 60 mg) and placebo in the treatment of duodenal ulcer
Authors: AVNER D. L. , DORSCH E. R. , JENNINGS D. E. , GRESKI‐ROSE P. A.
Published: July 2010

Background: Lansoprazole is a new proton pump inhibitor for the treatment of peptic ulcer disease. Methods: A double‐blind, multicentre study was undertaken in 2 9 6 patients with endoscopically proven duodenal ulcer to compare the efficacy and safety of lansoprazole 15, 30 or 60 mg with placebo. Ulcer healing was documented by endoscopy at 2 and 4 weeks; patients whose ulcers healed after 4 weeks were followed for up to 6 months post‐treatment.

Results: Four‐week healing rates of 89.4% 91.7% and 89.9% were obtained with lansoprazole 15, 30 and 60 mg, respectively, compared with 46.1 % on placebo (P < 0.001). All three doses of lansoprazole produced rapid symptom relief, although patients taking 60 mg lansoprazole required fewer antacids than did those taking 15 mg. At 6 months, the percentages of patients healed were 45.3%, 40.0% and 38.4% in the lansoprazole 15, 30 and 60 mg dosage groups, respectively, and 2 5.3 % for the placebo group. No significant adverse events were documented during the period of this trial.

Conclusion: Lansoprazole is an effective and safe treatment for duodenal ulcer and the 15 mg dose is as effective as 30 or 60 mg.
Erythromycin shortens orocaecal transit time in diabetic male subjects : a double‐blind placebo‐controlled study
Authors: MINOCHA A. , KATRAGADDA R. , RAHAL P. S. , RIES† A.
Published: July 2010

Background: The effects of erythromycin on small bows motility are controversial. Orocaecal transit time (OCTT) is considered to be a valid measure of small bowel motility.

Methods: We studied the effect of erythromycin on OCTT in diabetic male subjects in a double‐blind placebo‐controlled crossover fashion. After an overnight fast, subjects received erythromycin 500 mf 250 mg or placebo, on 3 different days. A standard solid meal containing 20 g lactulose was administered 30 min after the erythromycin ingestion. Exhaled breath was collected and hydrogen concentration was assessed over 5 h. Breath hydrogen concentrations for each session were analysed over time by a generalized logistic function generating a sigmoidal curve. Front transit time was recorded as the time point when a sustained rise in breath hydrogen concentration of at least 5 p.p.m. was first observed.

Results: The mean ± S.E.M. time taken for the front of the meal to reach the caecum was 92.5 ± 9.5, 86.1±16.5 and 62.3 ± 12.1 min for placebo, erythromycin 250 mg and erythromycin 500 mg, respectively. The OCTT was significantly decreased with erythromycin 500 mg compard to placebo (P< 0.05).

Conclusion: Oral administration of 500 mg erythromycin has prokinetic effect on orocaecal transit in male patients with diabetes mellitus.
Comparison of budesonide and 5‐aminosalicylic acid enemas in active distal ulcerative colitis
Authors: LÉMANN M. , GALIAN A. , RUTGEERTS P. , HEUVERZWIJN R. VAN , CORTOT A. , VITEAU J. M. , ELEWAUT A. , BELAICHE J. , FROGUEL E. , MODIGLIANI R.
Published: July 2010

Background: Budesonide is a new corticosteroid with high topical anti‐inflammatory activity but little systemic effect. The aim of the present study was to compare the efficacy and safety of budesonide enema (2 mg/100 mL) and 5‐ASA enema (mesalazine 1 g/ 100 mL) given for 4 weeks in the treatment of active distal ulcerative colitis and proctitis.

Methods: Ninety‐seven patients were studied in a multicentre single‐blind randomized group‐comparative trial. The primary efficacy variables were endoscopy and histopathology scores obtained at 0, 2 and 4 weeks. Clinical symptoms were the secondary efficacy variables. Haematology, chemistry and adverse events were the safety variables.

Results: Budesonide and 5‐ASA enemas both resulted in a significant improvement in endoscopy and histopathology scores but no difference could be demonstrated between the two treatment groups. There was also a significant improvement of symptoms (number of bowel movements per day, quality of stools, presence of blood and mucus, and state of well‐being) within both groups but no difference between the two treatment groups. The clinical remission rate at 4 weeks was, however, 38% for patients treated with budesonide enema but 60% for those treated with 5‐ASA enema (P= 0.03). No adverse events attributed to the study drugs were recorded in either of the groups.

Conclusions: Budesonide enema 2 mg/100 mL appears to be as efficient and well‐tolerated as 5‐ASA enema in the treatment of active distal ulcerative colitis and proctitis.
A comparative study of cisapride and ranitidine at controlling oesophageal acid exposure in erosive oesophagitis
Authors: POUDEROUX P. , KAHRILAS P. J.
Published: July 2010

Background: The severity of gastro‐oesophageal reflux disease is generally considered to be related to the extent of oesophageal acid exposure. Current therapies include antisecretory and prokinetic agents. We compared two of these, ranitidine and cisapride, in their ability to lower oesophageal acid exposure in patients with erosive oesophagitis.

Methods: Seven patients with Savary–Miller's grade II–IV oesophagitis and with oesophageal contact time ± 8% were studied. Mean lower oesophageal sphincter pressure was 4.6 mmHg. Oesophageal acid contact time was 25.6 ± 5.6%. Each patient received ranitidine 150 mg b.d., ranitidine 150 mg q.d.s., or cisapride 10 mg q.d.s. in a randomized 3‐way cross‐over design. Intra‐oesophageal pH was monitored during 24 h for each of these treatments in a controlled hospital environment, while consuming a high fat, high calorie diet.

Results: Cisapride and ranitidine at both doses decreased the acid contact time and the number of reflux episodes. However, a minority of patients treated with ranitidine, and none with cisapride, diminished their oesophageal acid contact time to a normal value of < 5%. No treatment significantly decreased nocturnal acid exposure.

Conclusion: In patients with severe gastro‐oesophageal reflux disease both cisapride and ranitidine demonstrably lower oesophageal acid exposure, but neither therapy predictably normalizes it.
Intravenous administration of lansoprazole: a preliminary study of dose ranging and eflcacy in upper gastrointestinal bleeding
Authors: AOKI T.
Published: July 2010

Using 24‐h pH monitoring, we studied the optimal dose and mode of administration of lansoprazole (LAN) injection in healthy adult male volunteers in three tests of antisecretory effect. We followed this with a dosefinding study, using the drug's suppressive effect on increased gastric acid secretion due to surgical stress as the indicator. Finally, we conducted a pilot study to determine the optimal mode of administration and efficacy of the drug in patients with haemorrhage from the upper gastrointestinal tract.

Twenty‐four‐hour intragastric pH monitoring established the order of potency of the different regimens: LAN 30 mg b.d. > LAN 15 mg bed.: and LAN 30 mg b.d., intravenous drip infusion = LAN 30 mg b.d., bolus injection.

Lansoprazole 30 mg b.d. appeared to be slightly more effective than LAN 15 mg b.d. in suppressing increased gastric acid secretion due to post‐operative stress and in haemostasis in patients with upper gastrointestinal bleeding. No severe adverse effects were observed in either study.
Review article: The medical management of Crohn's disease
Authors: ELTON E. , HANAUER S. B.
Published: July 2010

The choice of medical therapies for Crohn's disease continues to grow. Although our understanding of the mechanisms of the disease is incomplete, increasing knowledge of the pathogenesis of inflammation in general and Crohn's disease in particular allows targeting of therapies at various points in the immunoinflammatory cascade. In addition, the division of Crohn's disease into subtypes by location, aggressiveness, and the presence or absence of perianal and fistulizing disease allows the tailoring of medical therapy to the individual patient. For those patients with moderate to severe symptoms or frequent flares of disease activity, and those who have required surgical resection, maintenance therapy can substantially reduce the rate of recurrence. Despite these advances, available medical therapies for Crohn's disease remain imperfect, as evidenced by their sometimes substantial toxicities and the continued frequent need for surgery.
Clinical Economics Review: gastroenterology
Authors: BODGER K. , DALY M. J. , HEATLEY R. V. , WILLIAMS D. R. R.
Published: July 2010

In the prevailing climate of cost containment, doctors are increasingly expected to consider the economic consequences of treatment choices. Clinical (or medical) economics attempts to apply economic principles to the description and analysis of the costs of medical interventions, so as to identify how best to spend scarce health care resources. Such economic evaluations may assess the overall financial burden of a disease to society as a whole (macro‐economics), or attempt to compare alternative treatment strategies for a specific clinical situation (micro‐economics). In addition to expenditure on drugs and investigations (direct medical costs), economic studies may consider a variety of other costs. These include direct costs borne by patients (e.g. prescription charges, travel, food), indirect costs to society owing to lost productivity (resulting from morbidity or premature mortality) and even intangible costs which assign a monetary value to outcomes of disease such as pain, distress and anxiety.

Four main types of economic analysis are in current use.Cost minimization analysisattempts to identify the least expensive option in situations where there are a range of equally effective treatments for a given clinical condition, whereascost‐effectiveness analysisallows management strategies differing both in cost and efficacy to be compared. The cost‐effectiveness of health care programmes targeting different disease states may also be compared usingcost‐utility analysis, in which health benefits are translated into a common utility‐based unit of outcome, such as the Quality Adjusted Life Year (QALY).Cost‐benefit analysisattempts to quantify health outcomes in monetary terms, so that the net result provides an assessment of value‐for‐money of health interventions.

Gastrointestinal disorders are amongst the commonest of complaints, and considerable health care resources are consumed in treatment. Issues of cost‐effectiveness are likely to assume increasing importance in gastroenterologybecause of the everexpanding range of drug choice, the increasing number of high costtreatments and the development of new therapeuticinterventions.
Significance of activated mast cells in submucosa and muscularis propria of patients with Crohn's disease detected by a novel antimast cell surface molecule antibody
Authors: OSHITANI N. , KAMATA N. , INAGAWA M. , YAMAGAMI H. , WATANABE K. , FUJIWARA Y. , HIGUCHI K. , ARAKAWA T. , OKADA T.
Published: July 2010

Background

Degranulated mast cells may be missed by histochemical and immunohistological techniques, making the histological assessment of activated mast cells difficult.

Aim

To use a novel mast cell surface antigen 1 (MASA‐1) to detect activated mast cells.

Methods

Surgical samples of human intestine were obtained from 15 patients with ulcerative colitis (UC), 14 patients with Crohn's disease (CD) and 11 controls. Frozen sections were cut and MASA‐1 was detected and quantified by enzyme immunohistology. Immunohistological double staining with anti‐MASA‐1 and either anti‐CD68 or anti‐c‐Kit antibody was also performed.

Results

The number of MASA‐1‐positive cells was significantly higher in the submucosal layer and muscularis propria in patients with CD than in patients with UC or controls. The number of MASA‐1‐positive cells was significantly higher in the muscularis propria in patients with UC in highly inflamed colon compared with controls and less inflamed colon. Human intestinal MASA‐1‐positive cells are not from the macrophage lineage and showed heterogeneous expression of c‐Kit.

Conclusion

The increased number of mast cells in the submucosa and muscularis propria in patients with CD suggests that the involvement of activated mast cells in transmural inflammatory responses possibly including tissue remodelling.
Comparison of efficacies of dual therapy and triple therapy using rabeprazole in second‐line eradication ofHelicobacter pyloriin Japan
Authors: KAWAI T. , KAWAKAMI K. , KATAOKA M. , TAIRA S. , ITOI T. , MORIYASU F. , TAKAGI Y. , AOKI T. , RIMBARA E. , NOGUCHI N. , SASATSU M.
Published: July 2010

Background

The only authorized second‐lineHelicobacter pyloriregimen in Japan is proton pump inhibitor + amoxycillin + clarithromycin. However, it has been reported that this second‐line regimen is not effective. In this study, we evaluated the efficacy of dual and triple eradication therapies using rabeprazole as second‐lineH. pylorieradication regimens.

Aim

To evaluate the efficacy of dual and triple eradication therapies using rabeprazole as second‐lineH. pylorieradication therapy.

Methods

Sixty‐twoH. pylori‐positive patients with first‐line eradication failure were randomly assigned to two groups. The RAM group was administered rabeprazole 20 mg + amoxycillin 1500 mg + metronidazole 500 mg daily for 1 week. The RA group was administered rabeprazole 40 mg + amoxycillin 2000 mg daily for 2 weeks. Eradication ofH. pyloriinfection was determined by13C‐urea breath testing at 8 weeks after completion of treatment. Prior to treatment, amoxycillin, clarithromycin and metronidazole susceptibility, and CYP2C19 phenotype status were determined.

Results

Eradication rates for the RAM and RA groups were 97% and 74%, respectively. Eradication rates were not influenced by CYP2C19 phenotype in either group. Eradication rates for clarithromycin‐resistant patients were 100% in the RAM group and 77% in the RA group.

Conclusions

One week with RAM therapy and 2 weeks with RA therapy were effective as second‐line eradication therapy forH. pyloriinfection; moreover, RAM was more effective than RA therapy.