bluuebunny/crossref_metadata_2025 huggingface dataset:
Double‐blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis
Authors: KRUIS W. , SCHÜTZ E. , FRIC P. , FIXA B. , JUDMAIER G. , STOLTE M.
Published: October 2003

Background

Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis. As yet, there is no other existing alternative with proven efficacy. In light of the hypothesis that the intestinal environment may contribute to the pathophysiology of ulcerative colitis, a trial was conducted to test the effects of probiotic treatment with an oral preparation of non‐pathogenic E. coli.

Methods

A total of 120 patients with inactive ulcerative colitis were included in a double‐blind, double‐dummy study comparing mesalazine 500 mg t.d.s. to an oral preparation of viable E. coli strain Nissle (Serotype 06: K5: H1) for 12 weeks with regard to their efficacy in preventing a relapse of the disease. Study objectives were to assess the equivalence of the clinical activity index (CAI) under the two treatment modalities and to compare relapse rates, relapse‐free times and global assessment.

Results

The start and end scores of the CAI demonstrated no significant difference (P=0.12) between the two treatment groups. Relapse rates were 11.3% under mesalazine and 16.0% under E. coli Nissle 1917 (N.S.). Life table analysis showed a relapse‐free time of 103±4 days for mesalazine and 106±5 days for E. coli Nissle 1917 (N.S.). Global assessment was similar for both groups. Tolerability to the treatment was excellent and did not differ. No serious adverse events were reported.

Conclusions

From the results of this preliminary study, probiotic treatment appears to offer another option for maintenance therapy of ulcerative colitis. Additional support is provided for the hypothesis of a pathophysiological role for the intestinal environment in ulcerative colitis.
The management of failed dual or triple therapy for Helicobacter pylori eradication
Authors: RINALDI V. , ZULLO A. , PUGLIANO F. , VALENTE C. , DIANA F. , ATTILI A. F.
Published: October 2003

Background:

After each treatment for Helicobacter pylori infection there is an eradication failure rate ranging from 5 to 50%. Thus, the best therapy schedule and treatment regimen sequence have still to be identified.

Methods:

Patients with H. pylori infection were randomized to receive either a 1‐week triple therapy of omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tetracycline 500 mg b.d. (OCT; 78 patients) or a 2‐week dual therapy of omeprazole 20 mg b.d. and amoxycillin 1 g b.d. (OA; 75 patients). H. pylori infection at entry and eradication 4–6 weeks after therapy had ended were assessed by rapid urease test and histology on biopsies from the antrum and the corpus. When eradication did not occur with either the OCT or OA regimens, patients were switched over to the OA or OCT therapy, respectively. Eradication in these patients was assessed 4–6 weeks after conclusion of treatment by a further endoscopy.

Results:

H. pylori eradication was achieved in 67.9% (95% CI = 57.6–78.3%) of patients treated with the OCT regimen and in 75.7% (95% CI = 65.9–85.5%) of patients treated with the OA therapy (χ2 = 1.11; P = 0.29). Moreover, H. pylori eradication was achieved in 39.1% (95% CI = 19.2–59.1%) of patients re‐treated with the OA regimen and in 88.9% (95% CI = 74.4–100%) of patients re‐treated with the OCT therapy (χ2 = 8.52; P = 0.003). Thus, the overall success rate `per protocol' analysis in our study was 81.6% (95% CI = 72.9–90.3%) for the triple and dual therapy sequence and 97.3% (95% CI = 93.6–100%) for dual followed by triple therapy (χ2 = 8.14; P = 0.004).

Conclusions:

Our data found that H. pylori eradication with OA therapy after OCT therapy failure was poor, while that obtained with OCT after OA therapy was good.
Effects of oral cisapride on small bowel motility in irritable bowel syndrome
Authors: EVANS P. R. , BAK Y.‐T. , KELLOW J. E.
Published: October 2003

Background:

Cisapride has been reported to improve symptoms in patients with constipation‐predominant irritable bowel syndrome.

Aim:

To compare the effects of a 24‐h oral dose regimen of cisapride on interdigestive and post‐prandial small bowel motor activity in irritable bowel syndrome patients with predominant constipation, irritable bowel syndrome patients with predominant diarrhoea and healthy subjects.

Methods:

In 12 irritable bowel syndrome patients (11 females, aged 44 ± 12 years)—constipation‐predominant (irritable bowel syndrome‐C, n=5) and diarrhoea‐predominant (irritable bowel syndrome‐D, n=7)—and six healthy subjects, small bowel motor activity was continuously recorded using an ambulatory technique over a 48‐h period. Subjects received, in single‐blind fashion, placebo tablets q.d.s. in the first 24 h then cisapride 10 mg q.d.s. in the second 24 h. Additional control groups were 13 healthy subjects (eight females, aged 39 ± 13 years) and 10 irritable bowel syndrome patients (10 females, aged 49 ± 14 years) who were studied in identical fashion but who did not receive cisapride.

Results:

Cisapride increased migrating motor complex phase 2 motility index in both irritable bowel syndrome‐D (P < 0.01) and irritable bowel syndrome‐C (P < 0.05) patients, as well as in healthy subjects (P < 0.01). An increase in fasting discrete clustered contractions occurred in irritable bowel syndrome‐D patients (P < 0.001) and in healthy subjects (P < 0.01), but not in irritable bowel syndrome‐C patients; the proportion of discrete clustered contractions that were propagated, however, increased only in irritable bowel syndrome‐D patients (P < 0.001). In addition, cisapride resulted in an increase in post‐prandial motility index in irritable bowel syndrome patients (P < 0.05). Such motor alterations were not observed during the 48‐h recording period in the healthy or irritable bowel syndrome patient control groups who did not receive cisapride.

Conclusions:

Oral cisapride influences interdigestive and post‐prandial small bowel motor activity in both irritable bowel syndrome patients and healthy subjects; the effects of cisapride may be more marked in patients with predominant diarrhoea than in patients with predominant constipation.
Effects of 3‐days' intake of a sustained‐release preparation of the nitric oxide donor, isosorbide dinitrate, on oesophageal motility
Authors: STACHER G. , SCHNEIDER C. , STEINRINGER H. , HOLZÄPFEL A. , GAUPMANN G. , STACHER‐JANOTTA G.
Published: October 2003

Background:

Nitric oxide plays an important role in gastrointestinal motility. We evaluated the effects of a sustained‐release preparation of the nitric oxide donor isosorbide dinitrate on swallow‐initiated oesophageal contractions and the lower oesophageal sphincter.

Methods:

Twelve healthy men, aged 23–32 years, received, at 1‐week intervals and under random double‐blind conditions, for 3 days either 20 mg isosorbide dinitrate, 40 mg isosorbide dinitrate or placebo twice daily (b.d.). One hour after a further dose on day 4, oesophageal motility was recorded for 30 min using a multilumen catheter with a Dent sleeve straddling the lower oesophageal sphincter and side‐hole openings 0, 3, 6 and 9 cm proximal to the sleeve. Contractile responses to twelve 5‐mL water swallows were evaluated.

Results:

Amplitude, duration, propagation velocity and onset latency of oesophageal contractions were not affected by either dosage of isosorbide dinitrate. Lower oesophageal sphincter resting pressure was significantly lower after 40 mg (15.1 mmHg ± 1.2 S.E.M.) and 20 mg isosorbide dinitrate b.d. (15.0 ± 1.0 mmHg) than after placebo (17.9 ± 1.7 mmHg; P<0.025). Headache was reported by all subjects on 40 mg isosorbide dinitrate, seven subjects on 20 mg and by one on placebo.

Conclusions:

Twenty and 40 mg sustained‐release isosorbide dinitrate twice daily had no effect on swallow‐initiated oesophageal contractions but decreased lower oesophageal sphincter resting pressure.
Effects of oral rabeprazole on oesophageal and gastric pH in patients with gastro‐oesophageal reflux disease
Authors: ROBINSON M. , MATON P. N. , RODRIGUEZ S. , GREENWOOD B. , HUMPHRIES T. J.
Published: October 2003

Background

This study examined the dose–response effects of the new proton‐pump inhibitor rabeprazole on oesophageal and gastric pH in patients with gastro‐oesophageal reflux disease.

Methods

This study had a single‐centre, double‐blind, randomized, two‐way crossover design. Twenty patients were treated for two 7‐day periods separated by a 7–10‐day washout period. Patients were randomly assigned to receive either 20 mg of rabeprazole once daily during the first treatment period and 40 mg once daily during the second treatment period, or 40 mg during the first treatment period and 20 mg during the second treatment period. The primary efficacy variable was oesophageal acid exposure determined by 24‐hour ambulatory pH monitoring. Acid‐reflux time was defined as the percentage of time over 24 h that oesophageal pH was <4. A dosage was considered effective if reflux time was reduced to <6%, a number which has been our internal laboratory reference.

Results

Both rabeprazole 20 mg and 40 mg, given once daily, normalized reflux time, with decreases of 79% and 92% in acid exposure by day 7. Both dosages also decreased the mean total number of reflux episodes and the number of episodes lasting> 5 min, with no significant differences between dosages for any reflux parameter. Mean gastric pH increased with 20 mg from 1.86 at baseline to 3.71 on day 1 and 4.17 on day 7. Rabeprazole 40 mg once daily increased gastric pH from 2.01 to 4.37 on day 1, and to 4.65 on day 7. Safety analyses revealed no significant acute side‐effects for either dosage.

Conclusions

Pathological oesophageal acid exposure was normalized with both 20 mg and 40 mg dosages of rabeprazole, and the effects of these two doses did not differ. Rabeprazole was well‐tolerated in this short‐term study.
Aspirin causes rapid up‐regulation of cyclo‐oxygenase‐2 expression in the stomach of rats
Authors: DAVIES N. M. , SHARKEY K. A. , ASFAHA S. , MACNAUGHTON W. K. , WALLACE J. L.
Published: October 2003

Background:

Cyclo‐oxygenase‐1 (COX‐1) is believed to produce prostaglandins vital to mucosal defence, whereas cyclo‐oxygenase‐2 (COX‐2) is induced at sites of inflammation. Little is known about the regulation of COX‐2 in the stomach, particularly during the period following mucosal injury. In this study, we examined COX‐1 and COX‐2 expression shortly after administration of NSAIDs or ethanol.

Methods:

Fasted rats were given aspirin, salicylate, indomethacin or ethanol (20% or 40%) orally. Three hours later the stomach was excised, the severity of damage scored and samples taken for RT‐PCR of COX‐1 and COX‐2 mRNA and immunohistochemistry. Nitric oxide synthase mRNA (iNOS and eNOS) and activity were also measured.

Results:

Aspirin, indomethacin and the higher concentration of ethanol produced widespread mucosal damage, whereas salicylate and 20% ethanol caused only superficial epithelial damage. Aspirin caused a significant increase in COX‐2 mRNA expression and a marked increase in COX‐2 immunoreactivity, particularly in the superficial mucosa. Expression of COX‐1 (mRNA and protein) was unaffected by aspirin, as were NOS mRNA expression and enzyme activity. Pre‐treatment with prostaglandin E2 prevented the induction of COX‐2 by aspirin. Salicylate and indomethacin caused modest increases in COX‐2 immunoreactivity but no change in COX‐2 mRNA. Neither concentration of ethanol affected COX‐2 mRNA or protein expression, suggesting that this was a specific response to the aspirin, rather than to injury.

Conclusions:

These results demonstrate a rapid up‐regulation of COX‐2 expression in response to aspirin, possibly representing a compensatory response to inhibition of gastric prostaglandin synthesis.
Absence of gaseous symptoms during ingestion of commercial fibre preparations
Authors: ZUMARRAGA L. , LEVITT M. D. , SUAREZ F.
Published: October 2003

Background:

While fibre is believed to cause gaseous symptoms, a study in healthy volunteers showed no increase in flatulence when the diet was supplemented with fermentable (psyllium) or non‐fermentable (methylcellulose) fibre. However, extrapolation of this observation to subjects who use fibre is arguable since these individuals may have a propensity to gaseousness. In the present study, gaseous complaints during fibre ingestion were assessed in subjects who believed that a previous exposure to fibre induced gas.

Methods:

In a double‐blind protocol, subjects were randomized to one of four treatment periods, during which the regular diet was supplemented for 1‐week periods with two daily doses of: placebo 10 g, psyllium 3.4 g, methylcellulose 2 g or lactulose 5 g. A symptom diary was maintained for 1‐week periods on or off treatment.

Results:

During treatment, the lactulose group passed gas significantly more often than did the psyllium or the methylcellulose group (P=0.01). No other symptom was significantly different among the treatment groups.

Conclusions:

(1) psyllium and methylcellulose did not cause greater gaseous symptomatology than did placebo in subjects who believed that these preparations caused gas; and (2) subjects commonly misidentify dietary components that cause gaseous symptoms.
Use of a novel electronic data collection system in multicenter studies of irritable bowel syndrome
Authors: HARDING J. P. , HAMM L. R. , EHSANULLAH R. S. B. , HEATH A. T. , SORRELLS S. C. , HAW J. , DUKES G. E. , WOLFE S. G. , MANGEL A. W. , NORTHCUTT A. R.
Published: October 2003

Background:

The reliability of symptom data collected during efficacy studies in irritable bowel syndrome (IBS) is paramount to the proper assessment of potential therapeutic agents. Historically, data have been collected on paper diary cards, which patients were requested to fill out at a specified interval. However, with paper diary cards it is not possible to determine whether the cards are filled out as required, or at random times. To circumvent this problem, a novel electronic data collection system that ensures the reliability and security of data entry was used.

Methods:

Data were collected from 640 patients during the 2‐week screening and 12‐week treatment phases of two multicentre trials of IBS. The electronic data collection system used was based upon a touchtone telephone system.

Results:

The electronic data collection system had a potential 8135 up‐time hours during the study. An up‐time of 8040 h and down‐time of 95 h was observed. This corresponds to an up‐time of approximately 99%. Patient compliance for data entry in the two studies was 81% and 83%, respectively. On a single random day during their daily telephone call, patients were asked questions to assess satisfaction with the system. On aggregate, 79% of patients were satisfied or very satisfied with the system, only 10% were dissatisfied or very dissatisfied.

Conclusion:

A unique electronic data collection system was tested for use in clinical studies in IBS. This system provided 100% reliability as to the date of data entry, and data were not subject to modification once entered. This methodology represents a marked advancement in clinical studies of IBS.
Review article: the pharmacological inhibition of gastric acid secretion—tolerance and rebound
Authors: SANDVIK A. K. , BRENNA E. , WALDUM H. L.
Published: October 2003

During the last decade our understanding of the regulation of gastric acid secretion has changed considerably. The recognition that gastrin acts mainly by releasing histamine from the enterochromaffin‐like (ECL) cell is of major importance. It is now necessary to review and seek new explanations for the development of tolerance and for the post‐treatment acid hypersecretion that may be observed when treatment with acid‐secretory inhibitors is discontinued. Tolerance and rebound related to H2‐receptor antagonists has previously been explained as upregulation of gastrin and/or histamine H2‐receptors, and/or an increased parietal cell mass. Experimental evidence for these theories is scarce. On the other hand, tolerance can now be explained by a gastrin‐induced increase in ECL cell‐derived histamine at the parietal cell H2‐receptor competing with the antagonist. The lack of tolerance to proton pump inhibitors may be explained by their mode of action, being non‐competitive and acting at the H+, K+‐ATPase rather than at stimulatory receptors. Post‐treatment rebound acid hypersecretion can be understood as gastrin upregulating and/or stimulating growth of the ECL cell, leading to increased amounts of releasable histamine post‐treatment. Novel experimental data strongly support this view of the development of tolerance and post‐treatment rebound acid hypersecretion.
Oral budesonide therapy for steroid‐dependent ulcerative colitis: a pilot trial
Authors: KELLER R. , STOLL R. , FOERSTER E. C. , GUTSCHE N. , DOMSCHKE W.
Published: October 2003

Background:

Budesonide, a corticosteroid with high topical anti‐inflammatory activity and low systemic activity, has been shown to prolong time to relapse in Crohn's disease. In the present study, the efficacy of budesonide in an oral pH‐modified‐release formulation was evaluated for maintenance treatment in patients with steroid‐dependent ulcerative colitis.

Methods:

Fourteen patients with steroid‐dependent ulcerative colitis in the reduction phase of conventional glucocorticosteroids (c‐GCS) following a severe attack, were treated with budesonide 3 mg t.d.s. for 6 months. The primary investigation parameters were changes in the clinical activity index (CAI) and in the daily dose of c‐GCS.

Results:

In 11 cases the CAI improved significantly and treatment with c‐GCS could be terminated. Three patients experienced relapse and needed further c‐GCS treatment. The average daily dose of c‐GCS and the average value of the CAI before treatment with budesonide were significantly higher in the relapse group than in the remission group.

Conclusions:

In patients with c‐GCS‐dependent ulcerative colitis, a dose of 9 mg budesonide daily in an oral pH‐modified‐release formulation was well tolerated, significantly decreased the CAI, and rendered c‐GCS unnecessary in the majority of cases.
Intragastric pH after oral administration of single doses of ranitidine effervescent tablets, omeprazole capsules and famotidine fast‐dissolving tablets to fasting healthy volunteers
Authors: HEDENSTRÖM H. , ALM C. , KRAFT M. , GRAHNÉN A.
Published: October 2003

Background:

The therapeutic effect of drugs inhibiting acid production on acid‐related discomforts is related to both the onset and duration of action of the drug. The effects on gastric pH by single oral doses of some acid‐inhibiting drugs were investigated by measuring daytime (morning to lunch) intragastric pH in healthy volunteers.

Methods:

This randomized, single‐dose, 4‐way crossover study included 15 healthy fasting subjects. Effervescent ranitidine tablets 150 and 300 mg, fast‐dissolving famotidine tablets 20 mg and capsules of omeprazole 20 mg were administered. Measurements of intragastric pH were performed every 4 s for 10 min prior to drug administration and during the following 4 h.

Results:

The effervescent ranitidine tablets (150 or 300 mg) produced similar changes in intragastric pH: following an immediate increase to about pH 5, intragastric pH decreased slightly over the next 10–20 min. Thereafter pH increased steadily, reaching pH 4 after 20–40 min and pH 6 after about 70 min. After famotidine, pH 4 was reached after 80 min, significantly slower than ranitidine. After omeprazole, pH 3 was never reached. Ranitidine 150 and 300 mg showed significantly larger integrated pH responses over the 4‐h observation period, compared to famotidine (P=0.0288 and 0.0074) or omeprazole (P < 0.001).

Conclusions:

After single‐dose administration to healthy fasting volunteers), ranitidine effervescent tablets showed a significantly more rapid onset of action and a significantly larger integrated pH response compared to either famotidine 20 mg fast‐dissolving tablets or omeprazole 20 mg capsules.
Interaction of an aluminium–magnesium containing antacid and gastric mucus: possible contribution to the cytoprotective function of antacids
Authors: GRÜBEL P. , BHASKAR K. R. , CAVE D. R. , GARIK P. , STANLEY H. E. , LAMONT J. T.
Published: October 2003

Background: Antacids are generally thought to protect the gastric mucosa from damage primarily by their ability to neutralize hydrochloric acid, but recently other mechanisms of antacid cytoprotection have been suggested. The aim of our study was to determine if the antacid hydrotalcit (Mg6Al2(OH)16CO3×4H2O) and its clinical formulations Talcid (suspension and tablet) can influence the acid barrier properties of pig gastric mucus (PGM).

Methods: Viscosities, flow patterns of injected HCl, and permeability to HCl were assayed in solutions of PGM with and without added antacid.

Results: Talcid‐suspension markedly increased mucin viscosity between pH 2 and 7. In contrast, powdered Talcid‐tablet and hydrotalcit noticeably reduced mucin viscosity at pH 5 and below. HCl barely diffused through PGM‐Talcid‐suspension, whereas the acid was able to quickly penetrate a PGM‐Talcid‐tablet powder or PGM‐hydrotalcit mixture. When injected into a mixture of PGM‐Talcid‐suspension, HCl travelled in a single distinct channel whereas in both PGM‐Talcid‐tablet powder or PGM‐hydrotalcit mixtures, the acid mixed irregularly throughout. Experiments with antacids alone revealed that Talcid‐suspension, but not Talcid‐tablet nor hydrotalcit, had barrier properties similar to PGM.

Conclusion: Talcid‐suspension has viscoelastic features similar to gastric mucin and may afford mucosal protection by its ability to maintain or mimic the barrier properties of gastric mucus gel. In contrast, powdered Talcid‐tablets and hydrotalcit reduce the barrier function of gastric mucus.
Prevention of heartburn relapse by low‐dose famotidine: a test meal model for duration of symptom control
Authors: MANN S. G. , COTTRELL J. , MURAKAMI A. , STAUFFER L. , RAO A. N.
Published: October 2003

Aim: To establish whether patients taking famotidine 10 mg to treat an episode of heartburn were protected from a recurrence of symptoms after a subsequent test meal.

Methods: Frequent heartburn sufferers (n=366) were randomized to receive double blind treatment with famotidine 10 mg or 2×250 mg chewable alginate tablets within 30 min of a spontaneous episode of heartburn. After 4 h, patients with no or slight residual symptoms consumed a meal likely to induce heartburn. Over the next 4 h patients recorded the severity of heartburn and any consumption of ‘rescue’ antacids. At the end of this time they rated the global efficacy of their treatment in controlling meal‐induced symptoms.

Results: Study groups were well matched for all baseline characteristics. Of the 366 randomized patients, 276 took study medication and data from 269 patients (132 famotidine, 137 alginate) were analysed for efficacy. Compared to the alginate control group famotidine treated patients reported better global efficacy following the test meal (P<0.001; relative odds for a more favourable response: 2.26 [95% CI: 1.45–3.53]). Fewer patients receiving famotidine resorted to antacid rescue (P = 0.038; relative odds for a more favourable response: 2.24 [95% CI: 1.04–4.79]) and peak heartburn was significantly less severe with famotidine treatment (P<0.001; relative odds for a more favourable response: 2.90 [95% CI: 1.85–4.53]). Eleven famotidine‐treated patients (8%) and 13 alginate patients (9%) reported adverse events.

Conclusion: Compared to patients receiving an alginate preparation, patients self medicating with famotidine 10 mg for heartburn are better protected against a recurrence of their symptoms when they next eat. This suggests that the duration of acid control (9 h) previously demonstrated with this dose translates into a similar duration of measurable symptom control during the day.
Ranitidine bismuth citrate and clarithromycin twice daily in the eradication of Helicobacter pylori
Authors: AXON A. T. R. , IRELAND A. , LANCASTER SMITH M. J. , ROOPRAM P. D.
Published: October 2003

Background: Ranitidine bismuth citrate (RBC) 400 mg when given twice daily (b.d.) for 4 weeks with clarithromycin 250 mg four times daily (q.d.s.) for the first 2 weeks effectively heals duodenal ulcers and eradicates Helicobacter pylori.

Aims: To compare two dosage regimens of clarithromycin, 250 mg q.d.s. and 500 mg b.d., used with ranitidine bismuth citrate (Pylorid) 400 mg b.d., for the eradication of H. pylori and for symptom relief in patients with active duodenal ulcers.

Subjects: 236 patients with active duodenal ulcer and confirmed H. pylori infection.

Methods: In a randomized, double‐blind, parallel group, multi‐centre study, RBC was given with clarithromycin for 2 weeks followed by 2 weeks treatment with RBC alone to allow for ulcer healing. Ulcer status was assessed by endoscopy at entry. H. pylori status was assessed by CLO Test and 13C‐urea breath test (UBT) at entry and UBT alone 4 weeks after the end of treatment. At entry, during the study and at follow‐up, ulcer symptoms were recorded on a scale of none, mild, moderate or severe.

Results: 176 patients had an evaluable UBT at least 4 weeks post‐treatment. H. pylori eradication rates were 96.2% for the RBC plus clarithromycin b.d. regimen and 91.8% for the RBC plus clarithromycin q.d.s. regimen (observed data). Four weeks post‐treatment, 92% of patients receiving RBC b.d. plus clarithromycin q.d.s. and 89% receiving RBC b.d. plus clarithromycin b.d. were considered symptom successes (none or mild symptoms).

Conclusions: RBC 400 mg b.d. plus clarithromycin 500 mg b.d. was as effective as RBC 400 mg b.d. plus clarithromycin 250 mg q.d.s. in eradicating H. pylori and both regimens were well tolerated. The simpler dual therapy in a b.d. regimen might well encourage greater patient compliance.
Review article: insurance risks for patients with ulcerative colitis or Crohn's disease
Authors: TRAVIS S. P. L.
Published: October 2003

Prospective population‐based studies have allowed a re‐evaluation of the risks of insuring patients with ulcerative colitis or Crohn's disease. Life expectancy, the risk of cancer and working capacity are very much better than previously recognised and are normal for many patients. Three population‐based studies in ulcerative colitis have shown a mortality similar to or slightly less than the general population except in the first year after diagnosis, whilst two have shown a slightly higher mortality (standardized mortality ratio, SMR=1.4), except for those with proctitis. In Crohn's disease, two population‐based studies have also shown an increased mortality (SMR=1.4), which is similar to that of unskilled manual labourers (SMR=1.43) from all causes of death. Three other studies have shown no increase in overall mortality, except in the first 5 years after diagnosis, in those with proximal small intestinal disease and in some patients needing multiple operations. Insurance risks should be evaluated on an individual basis, after details of the extent and pattern of disease have been obtained. Although the ‘standard life’ in insurance terms differs from that of the general population, because people who seek life assurance are self‐selected from a more affluent section of society, many patients can be identified who have a particularly good prognosis. These include patients with ulcerative proctitis, those with left‐sided colitis in extended remission (>12 months), and patients more than 30 years old with localized ileal or ileocaecal Crohn's disease that has responded to treatment. From the published data, it is difficult to justify increasing the insurance premium in such patients.
Ursodeoxycholic and tauro‐ursodeoxycholic acids for the treatment of primary biliary cirrhosis: a pilot crossover study
Authors: LARGHI A. , CROSIGNANI A. , BATTEZZATI P. M. , DE VALLE G. , ALLOCCA M. , INVERNIZZI P. , ZUIN M. , PODDA M.
Published: October 2003

Background: Results from animal studies and preliminary data from pilot studies in patients with primary biliary cirrhosis suggest that tauro‐ursodeoxycholic acid has metabolic properties that may favour its long‐term use as an alternative to ursodeoxycholic acid for patients with chronic cholestatic liver diseases. No direct comparison of tauro‐ursodeoxycholic and ursodeoxycholic acids have yet been carried out in primary biliary cirrhosis.

Methods: The effects of ursodeoxycholic and tauro‐ursodeoxycholic acids were compared in 23 patients with primary biliary cirrhosis according to a crossover design. Both drugs were administered at the daily dose of 500 mg, in a randomly assigned sequence for two 6‐month periods separated by a 3‐month wash‐out period.

Results: Serum liver enzymes related to cholestasis and cytolysis consistently improved, as compared to baseline values, during the administration of both ursodeoxycholic and tauro‐ursodeoxycholic acids, but no significant difference between these two bile acids was found. Both treatments were well tolerated and no patient complained of side effects.

Conclusion: In the short‐term, tauro‐ursodeoxycholic acid appears to be safe and at least as effective as ursodeoxycholic acid for the treatment of primary biliary cirrhosis.
The safety of ranitidine in over a decade of use
Authors: MILLS J. G. , KOCH K. M. , WEBSTER C. , SIRGO M. A. , FITZGERALD K. , WOOD J. R.
Published: October 2003

Background: Ranitidine hydrochloride (Zantac) is one of the most extensively studied and widely used drugs of all time. This has provided an excellent opportunity to define its safety profile.

Methods: Data from 189 controlled clinical trials in which more than 26000 patients received daily doses of ranitidine for 4 weeks or more were reviewed. More than 80% of patients were treated with up to 300 mg ranitidine daily; the remaining patients received doses of up to 1200 mg daily. Eighty‐seven trials were placebo controlled. Analyses of post‐marketing surveillance and a database of all spontaneously reported adverse events were also evaluated.

Results: Overall in the clinical trial programme adverse events were reported by 20% of those receiving ranitidine compared with 27% of those receiving placebo. The pattern of events was similar in all treatment groups with no evidence of dose‐related toxicity in regimens encompassing an eightfold range of therapeutic doses. Similarly in a programme of studies designed to evaluate a dose of ranitidine of 75  mg for non‐prescription (over‐the‐counter) use in the treatment of heartburn, ranitidine was not associated with an adverse event profile distinct from that of placebo. Analysis of spontaneously reported adverse event data allowed identification of rare idiosyncratic events.

Conclusions: Review of data from a large population of controlled clinical trials with analyses of postmarketing surveillance studies and spontaneously reported adverse events confirmed the excellent safety profile of ranitidine.
Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi‐centre double‐blind study
Authors: SONTAG S. J. , ROBINSON M. , ROUFAIL W. , HIRSCHOWITZ B. I. , SABESIN S. M. , WU W. C. , BEHAR J. , PETERSON W. L. , KRANZ K. R. , TARNAWSKI A. , DAYAL Y. , BERMAN R. , SIMON T. J.
Published: October 2003

Introduction: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing.

Aim: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole.

Patients and methods: Patients whose active erosive reflux oesophagitis (grade 2) had healed (grade 0 or 1) after 4–8 weeks of open‐label omeprazole 40 mg daily (phase I) were eligible to join a multi‐centre, 6‐month double‐blind, placebo‐controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n=138), 20 mg omeprazole for 3 consecutive days each week (n=137), or placebo (n=131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse.

Results: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3‐days‐a‐week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P<0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3‐days‐a‐week (P<0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells.

Conclusions: These results show that after healing of erosive oesophagitis with 4–8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.
The effect of intravenous erythromycin on solid meal gastric emptying in patients with chronic symptomatic post‐vagotomy–antrectomy gastroparesis
Authors: KENDALL B. J. , CHAKRAVARTI A. , KENDALL E. , SOYKAN I. , McCALLUM R. W.
Published: October 2003

Background: Chronic symptomatic gastroparesis occurs in 3–5% of patients following vagotomy and antrectomy. Erythromycin, a macrolide antibiotic, improves gastric emptying in patients with idiopathic and diabetic gastroparesis. Erythromycin's effect on gastric emptying in patients with post‐vagotomy– antrectomy gastroparesis is unknown. The aim of this study was to determine if a single dose of intravenous erythromycin (1 mg/kg or 6 mg/kg) accelerates solid meal gastric emptying in patients with chronic symptomatic post‐vagotomy–antrectomy gastroparesis.

Methods: Six patients were entered into the study, three males and three females, with a mean age of 50 years. Four patients were randomized to receive erythromycin 6 mg/kg and two patients 1 mg/kg. The mean time since initial surgery was 9.2 years (range 1–16 years) with five patients having undergone a Roux‐en‐Y revision.

Results: Intravenous erythromycin significantly lowered percentage gastric retention at 120 min, from a baseline of 90.5±6% (S.E.M.) to 40.1±4.8% after erythromycin (P=0.0002). Erythromycin improved gastric emptying in each patient by at least 40%. Intravenous erythromycin significantly accelerated the rate of gastric emptying in the first 30 min after meal ingestion from a baseline rate of 0.072±0.06%/min to 0.96±0.31%/min after erythromycin (P=0.028). For each of the subsequent 30 minute time periods, erythromycin had no significant effect on the rate of gastric emptying.

Conclusion: Intravenous erythromycin significantly improves the initial phase of solid meal gastric emptying in patients with chronic symptomatic post‐antrectomy–vagotomy gastroparesis.
Review article: platelets in inflammatory bowel disease— pathogenetic role and therapeutic implications
Authors: COLLINS C. E. , RAMPTON D. S.
Published: October 2003

An elevated platelet count is well recognized as a marker of inflammatory bowel disease activity. There is an increased incidence of systemic thromboembolism in this disease. Recent work indicates that platelets exhibit several proinflammatory properties including release of inflammatory mediators, and recruitment, chemotaxis and modulation of the activity of other inflammatory cells. Furthermore there is evidence that microvascular thrombosis and a procoagulant state may play a role in the pathogenesis of inflammatory bowel disease.

These observations prompted recent studies of platelet activity in inflammatory bowel disease, which indicate enhanced platelet aggregation in vivo and in vitro, and increased platelet activation as measured by increased release of intracellular proteins into plasma and expression of platelet surface markers, including P‐selectin and GP53. These abnormalities could contribute to the pathogenesis of inflammatory bowel disease by enhancing inflammation and promoting microinfarction. Aminosalicylates reduce platelet activity although they also have many other additional properties to explain their efficacy in inflammatory bowel disease. There are however several specific anti‐platelet drugs now available which may provide new therapeutic possibilities in the management of this disease.
Lansoprazole versus omeprazole: influence on meal‐stimulated gastric acid secretion
Authors: DAMMANN H. G. , FUCHS W. , RICHTER G. , BURKHARDT F. , WOLF N. , WALTER Th. A.
Published: October 2003

Aims: To investigate, by means of meal‐stimulated acid secretion, the extent to which differences in plasma half‐life, bioavailability and the recommended therapeutic dose can influence the antisecretory potency of lansoprazole and omeprazole.

Methods: In this double‐blind, placebo‐controlled, crossover study, 10 healthy male volunteers received 15 mg or 30 mg lansoprazole, 20 mg or 40 mg omeprazole or placebo for 5 days, in a randomized order. Meal‐stimulated acid secretion was determined by means of a homogenized test meal and intragastric titration.

Results: On day 1, meal‐stimulated acid secretion was decreased by 35% and 45% after administration of 15 mg or 30 mg lansoprazole, and by 16% and 42% after 20 mg or 40 mg omeprazole. After 3 and 5 days of dosing the decreases were 53% and 48% with 15 mg lansoprazole, 82% and 82% with 30 mg lansoprazole, 43% and 39% with 20 mg omeprazole, and 76% and 83% with 40 mg omeprazole. At all measuring points during the 5‐day dosing periods, lansoprazole 15 mg and 30 mg proved superior to 20 mg omeprazole in inhibiting meal‐stimulated gastric acid secretion, but the differences were only statistically significant for the lansoprazole 30 mg dose. 30 mg lansoprazole and 40 mg omeprazole proved equipotent. On day 1 only 30 mg lansoprazole was significantly better than placebo.

Conclusion: This study demonstrated the following order of antisecretory potency: 30 mg lansoprazole=40 mg omeprazole>15 mg lansoprazole≈20 mg omeprazole.
In single doses ranitidine effervescent is more effective than lansoprazole in decreasing gastric acidity
Authors: ARNESTAD J. S. , KLEVELAND P. M. , WALDUM H. L.
Published: October 2003

Background: A rapid and reproducible decrease of gastric acidity is preferable in patients with penetrating/perforating peptic ulcers and in on‐demand treatment of some patients with dyspepsia. The present study was done to compare the effect of single doses of ranitidine effervescent with that of the proton pump inhibitor lansoprazole.

Method: Twelve healthy young volunteers were studied by 11‐h intragastric continuous pH recording after the intake of ranitidine 150 or 300 mg effervescent tablets or lansoprazole 30 mg capsules. Trial medications were taken with 200 mL water, and the subjects remained fasting apart from 250 mL fluid at 4 h.

Results: Ranitidine effervescent, both 150 and 300 mg, induced a rapid and persisting increase in gastric pH in most of the subjects, whereas a single dose of lansoprazole 30 mg did not affect intragastric pH in five of the twelve subjects.

Conclusion: The histamine H2‐blocker ranitidine given as an effervescent formulation is superior to the proton pump inhibitor lansoprazole in inducing a rapid decrease of gastric acidity.
Clinical economics review: cost‐effectiveness in the therapy of liver disease
Authors: NEUBERGER J. , BRYAN S.
Published: October 2003

There have been many advances made in the management of patients with liver disease both in diagnosis and in the treatment of underlying liver disease and its complications, although comparatively few of these have been rigorously subjected to full cost‐effectiveness evaluation. In this review, we have analysed a small number of the therapeutic interventions; while these have been well evaluated clinically, very few have been analysed from the view‐point of cost‐effectiveness and, thus, it is difficult to make many definitive claims. It is hoped that future studies will consider these aspects as well.
Somatostatin receptor scintigraphy in the initial staging of Hodgkin's disease
Authors: Van Den Anker‐Lugtenburg P. J. , Krenning E. P. , Oei H. Y. , Van Hagen M. P. , Gerrits C. J. H. , Reubi J. C. , Lamberts S. W. J. , Löwenberg B.
Published: October 2003

Somatostatin receptor (SS‐R) scintigraphy has been successfully used in the visualization of a variety of neuroendocrine tumours. In vitro studies have shown that SS‐Rs are present in human malignant lymphomas. We conducted a prospective study in 56 consecutive untreated patients with histologically proven Hodgkin's disease (HD) and compared the results of SS‐R scintigraphy with physical and radiological examinations as initial evaluation.

SS‐R scintigraphy was positive in 55/56 (98%) patients at sites of documented disease. In 20 patients SS‐R scintigraphy disclosed lymphoma localizations not revealed following procedures of conventional staging. As a result in 12 patients (21%) SS‐R scintigraphy produced a change of stage and in seven patients (13%) the additional information obtained from SS‐R scintigraphy led to a change of treatment. SS‐R scintigraphy failed to visualize sites of HD in four patients, mainly in the abdominal area. In three patients a false‐positive result was obtained.

These data show that SS‐R scintigraphy provides an imaging technique that appears to visualize tumours in most patients with HD and may be clinically useful in the management of these patients.
Optimally functional fluorescein isothiocyanate‐labelled fibrinogen for quantitative studies of binding to activated platelets and platelet aggregation
Authors: XIA Z. , Wong T. , Liu Q. , Kasirer‐Friede A. , Brown E. , Frojmovic M. M.
Published: October 2003

Dynamic and quantitative studies of the binding of fibrinogen (Fg) to its receptor, GPIIb–IIIa, on activated platelets, leading to platelet aggregation, are best studied with fluorescently‐labelled Fg by flow cytometry. Due to conflicting reports on the functionality of FITC‐labelled Fg, we have developed a reproducible and ‘mild’ labelling of fibrinogen with FITC‐celite at pH 7.4–8.5 for direct and dynamic studies of specific Fg binding to activated platelets evaluated for native platelet‐rich plasma, for washed platelets, and for activated, fixed platelets. We have demonstrated the equivalence of FITC‐labelled and unlabelled Fg for binding to activated GPIIb–IIIa receptors, and in the rate and extent of mediating platelet aggregation. We found that FITC‐Fg labelled at pH ≥9 had reduced to absent specific binding to activated platelets, whether using soluble FITC or FITC‐celite. The FITC‐labelled Fg must be diluted 3‐fold with unlabelled Fg when evaluating maximal Fg binding to activated platelets in order to prevent autoquenching of the FITC‐Fg which leads to underestimation of Fg levels. The dissociation constant (KD) of Fg on stable preparations of activated, fixed platelets, determined with FITC‐Fg binding to platelets by flow cytometry, was in the range reported for 125I‐labelled Fg, 70–255 nm with Bmax = 10 000–25 000 Fg per platelet (n  = 20). The FITC‐Fg was used to monitor Fg binding to activated platelets directly in plasma, as well as to evaluate platelet subpopulations which maximally bind Fg according to the concentration of ADP used as activator. It is expected that this ‘mildly’ labelled FITC‐Fg will stimulate further studies of platelet activation directly in native anticoagulated blood/plasma, for both basic and clinical research.
Beta2‐glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant
Authors: Brighton T. A. , Hogg P. J. , Dai Y‐P. , Murray B. H. , Chong B. H. , Chesterman C. N.
Published: October 2003

Although the physiological role of beta2‐glycoprotein I (B2GPI) is unknown, in vitro evidence indicates that B2GPI may be a natural anticoagulant. In this study we have examined whether fluctuations of plasma B2GPI occur in in vivo coagulation. Serial measurements of B2GPI and other anticoagulant proteins were performed in 51 patients with thrombotic (group 1: six patients with disseminated intravascular coagulation (DIC), group 2: venous (n=4) or arterial (n=17) thrombosis) and non‐thrombotic disease (group 3: 24 patients undergoing elective surgery). Reductions in plasma B2GPI levels were seen in most patients which were roughly proportional to the severity of their illness. Particularly striking reductions of B2GPI, protein C (PC) and antithrombin III (AT‐III) (mean ± 95% CI: 42.7 ± 8.6%, 42.1 ± 14.8%, 39.1 ± 28.4% respectively) were seen in group 1. The reductions in plasma B2GPI were significantly greater in group 1 than in the other groups. Dilutional factors explain most of the reductions in B2GPI, PC and AT‐III in groups 2 and 3, but contribute little to group 1. In conclusion, although B2GPI behaves as a ‘negative acute phase reactant’, the magnitude of reduction of plasma B2GPI levels, accompanied by reductions in other anticoagulant proteins in patients with DIC, suggests specific consumption of B2GPI in in vivo coagulation. This study provides further evidence that B2GPI is an anticoagulant of physiological importance.
Clinical and laboratory factors associated with platelet transfusion refractoriness: a case–control study
Authors: Alcorta Iñaki , Pereira Arturo , Ordinas Antonio
Published: October 2003

In recent years clinical factors have largely surpassed alloimmunization as the predominant cause of platelet refractoriness. This makes it necessary to properly identify and weigh the non‐immune factors that have a major impact on refractoriness. A case–control study is suitable for such an analysis, and to our knowledge has not previously been performed to assess this issue.

Fifty‐two refractory patients were compared with 52 control patients who were transfused at the same time. Only one transfusion event was analysed per patient. Clinical and laboratory data were recorded at the time of selected transfusion, and their association with refractoriness was investigated by the contingency table method and the Cox stepwise logistic regression.

There were 16 (31%) patients with HLA antibodies in the index group and only one in the control group. The corrected count increment in the group of patients refractory due to HLA antibodies was significantly lower than that in non‐alloimmunized refractory patients [median (range): 48.5 (−3560, 4614) and 4058 (−4417, 6886), respectively; U = 493, P < 0.0001]. In the multivariate analysis, factors associated with refractoriness were the presence of HLA antibodies (odds ratio (OR) 50.7; 95% CI 5.5–463); fever (odds ratio 7.2; 95% CI 2.5–21) and BMT because of chronic myeloid leukaemia (odds ratio 7.3; 95% CI 1.8–30). The latter two were the only factors that remained independently associated with refractoriness after excluding alloimmunized patients and their controls.

We conclude that HLA antibodies are strongly associated with platelet transfusion refractoriness, but account for less than a third of these patients. Fever and BMT because of chronic myeloid leukaemia were the only non‐immune factors independently associated with refractoriness.