bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre‐neoplastic states of the gastric mucosa–a practical approach for the perplexed clinician
Authors: Genta R.M. , Rugge M.
Published: March 2003

The sequence leading to gastric cancer can be schematically reduced to Helicobacter pylori infection–chronic gastritis–atrophy–intestinal metaplasia–dysplasia–neoplasia. Although clinicians have not yet developed a uniform approach to the treatment of gastritis (when should H. pylori infection be treated?), the entity itself is not the subject of controversy. All other lesions are still the focus of debate. There are no guidelines for the management of patients with intestinal metaplasia; pathologists are still searching for universal diagnostic criteria for atrophic gastritis; dysplasia and early neoplasia have elicited scientific diatribes between Japanese and Western pathologists. Amidst such controversies and in the absence of guidelines to regulate the management of gastric lesions, the responsibility to provide sensible clinical advice is often bestowed upon pathologists.

This review discusses whether pathologists have access to sufficient evidence to provide the requested advice, and whether a consensus on the management of gastric ‘pre‐neoplastic’ states is within reach. We conclude that, although many sensible and useful definitions, criteria and classifications are being generated, the final decision on how to manage the individual patient with gastric lesions will continue to be based on the communication between pathologist and clinician.
A dose‐ranging, placebo‐controlled, randomized trial of alosetron in patients with functional dyspepsia
Authors: Talley N. J. , Van Zanten S. V. , Saez L. R. , Dukes G. , Perschy T. , Heath M. , Kleoudis C. , Mangel A. W.
Published: March 2003

Background:

Functional dyspepsia is characterized by upper abdominal pain or discomfort.

Aim:

To assess the benefit of the 5‐HT3‐receptor antagonist alosetron in a pilot, dose‐ranging, placebo‐controlled, multicentre, randomized clinical trial.

Methods:

A total of 320 functional dyspepsia patients received placebo (n=81), or alosetron 0.5 mg b.d. (n=77), 1.0 mg b.d. (n=79) or 2.0 mg b.d. (n=83) for 12 weeks, followed by 1 week of follow‐up. Primary efficacy was the 12‐week average rate of adequate relief of upper abdominal pain or discomfort. Secondary endpoints assessed pain and upper gastrointestinal symptoms.

Results:

Twelve‐week average rates of adequate relief of pain or discomfort were 46% (95% CI: 37–54%), 55% (95% CI: 46–63%), 55% (95% CI: 47–64%) and 47% (95% CI: 38–55%) in the placebo, 0.5 mg, 1.0 mg and 2.0 mg alosetron groups, respectively. Alosetron 0.5 mg or 1.0 mg showed potential benefit over placebo for early satiety and postprandial fullness. Females showed greater responses compared to males. Patients with adequate relief had significantly (P < 0.001) greater reductions in severity and frequency of functional dyspepsia symptoms than those without adequate relief. Constipation was the most commonly reported adverse event.

Conclusions:

Alosetron showed potential benefit in relieving functional dyspepsia symptoms compared to placebo. Patients with adequate relief of upper abdominal pain or discomfort showed improvements in multiple functional dyspepsia symptoms.
Effect of nabumetone and aspirin on colonic mucosal bleeding time
Authors: Basson M. D. , Panzini L. , Palmer R. H.
Published: March 2003

Background:

The management of patients taking aspirin or non‐steroidal anti‐inflammatory drugs (NSAIDs) who require colonoscopy remains controversial because of concerns over bleeding after biopsy or polypectomy.

Aim:

To determine whether patients using the NSAID nabumetone, a non‐acidic prodrug with mixed activity against cyclooxygenase‐1 (COX‐1) and COX‐2, exhibited prolonged mucosal bleeding times and how this might compare with mucosal bleeding times in patients using aspirin.

Methods:

We assessed triplicate mucosal bleeding times in patients undergoing screening flexible sigmoidoscopy. We compared 90 patients who had taken no aspirin or NSAIDs within the previous 2 weeks, to 60 patients who had received nabumetone 1 g b.d. by mouth for the previous 2 weeks, and 30 patients who had taken 325 mg aspirin daily for the previous 2 weeks. In each case, the investigator performing the study was blinded to the patient’s medication.

Results:

Mucosal bleeding times did not differ significantly among control or nabumetone‐using patients. However, the patients receiving aspirin exhibited significant prolongation. Mucosal bleeding time correlated statistically significantly, but weakly, with skin bleeding time.

Conclusions:

Nabumetone does not appear to prolong mucosal bleeding time after mucosal pinch biopsy, and skin bleeding time does not reliably screen for prolonged mucosal bleeding time.
The management of severe Crohn’s disease
Authors: Parkes M. , Jewell D. P.
Published: March 2003

The treatment of severe and active Crohn’s disease is currently based on immunosuppression, but also involves the management of nutrition, appropriate selection of patients for surgery, and maintenance of remission in the long term. Corticosteroids remain the drug of the first choice, particularly in the acute setting. However, there is evolving understanding of the role of other immunosuppressants and immune modifiers, as major concerns regarding side‐effects and efficacy of steroids in the medium to long‐term drive the search for alternatives.
Rapid detection of anti‐Helicobacter pylori IgG in urine using immunochromatography
Authors: Graham D. Y. , Reddy S.
Published: March 2003

Background:

Non‐invasive methods to detect the presence of H. pylori infection continue to be refined.

Aim:

To evaluate a new 20‐min immunochromatography method (RAPIRUN H. pylori Antibody) for the presence of anti‐H. pylori IgG in urine.

Methods:

We used the 13C‐urea breath test to establish H. pylori status. We evaluated the urine test among 104 subjects including 43 with H. pylori infection confirmed by repeatedly positive urea breath tests and 61 H. pylori‐negative subjects with repeatedly negative urea breath tests. Forty‐one of the 43 subjects with H. pylori infection had a positive rapid urine test with two false negative tests. There were two false positive tests among the 61 with repeatedly negative urea breath tests. The sensitivity, specificity, positive and negative predictive values for the rapid urine test were 95.3%, 96.7%, 95.3%, and 96.7%, respectively. The kit was easy to use and required no special equipment.

Conclusions:

The rapid immunochromatography method for determination of anti‐H. pylori IgG proved to be reliable with excellent sensitivity and specificity and is likely to be useful for both clinical and epidemiological studies.
Surveillance colonoscopy or chemoprevention with COX‐2 inhibitors in average‐risk post‐polypectomy patients: a decision analysis
Authors: Arguedas M. R. , Heudebert G. R. , Wilcox C. M.
Published: March 2003

Objectives:

Clinical trials are currently underway evaluating the efficacy of COX‐2 inhibitors in decreasing the incidence of adenomas and colorectal carcinoma in ‘average’ risk individuals.

Aim:

To use decision analysis to compare the cost‐effectiveness of celecoxib to surveillance colonoscopy in ‘average’ risk patients who had undergone prior adenoma resection.

Methods:

A model of the natural history of adenomas after endoscopic polypectomy was constructed using probabilities from the literature. Cost estimates were obtained from available Medicare reimbursement rates and supplemented by the literature. Three strategies were evaluated: (i) no surveillance; (ii) colonoscopic surveillance; and (iii) celecoxib chemoprevention. We compared total costs and performed cost‐effectiveness analysis between these strategies. The outcome measures were years of life saved and ‘high‐grade’ adenoma prevented. Sensitivity analyses were performed on selected variables.

Results:

Our base‐case analysis assumed a 50% risk reduction in the incidence of adenomas among patients using celecoxib. No surveillance was associated with a cost of $1014 per patient, and colonoscopic surveillance with a cost of $1572 per patient, whereas celecoxib use was associated with a total cost of $11 503. Ten years after the index colonoscopy, 15% of patients in the no surveillance strategy developed ‘high‐grade’ lesions compared to 13% of patients in the colonoscopic surveillance group and 6% in the celecoxib group. There was a small gain in years of life saved (0.006) favouring celecoxib over colonoscopic surveillance. The incremental cost‐effectiveness ratio of celecoxib vs. colonoscopy was $141 871 per ‘high‐grade’ adenoma prevented and $1 715 199 per year of life saved. The most important variables in determining the cost‐effectiveness of celecoxib were its cost and its efficacy.

Conclusion:

Chemoprevention with COX‐2 inhibitors in ‘average‐risk’ postpolypectomy patients is a more expensive strategy compared to colonoscopic surveillance.
A randomized controlled crossover study comparing synthetic porcine and human secretins with biologically derived porcine secretin to diagnose Zollinger–Ellison Syndrome
Authors: Metz D. C. , Buchanan M. , Purich E. , Fein S.
Published: March 2003

Background:

Although biologically‐derived porcine secretin is approved for the diagnosis of Zollinger–Ellison Syndrome, it is no longer available in the United States. Pure human and porcine secretins have now been synthesized and new drug applications have been filed with the Federal Drug Administration (FDA).

Methods:

In the current study we compared secretin testing results in six confirmed Zollinger–Ellison Syndrome patients using the biologically‐derived product and both synthetic products (human and porcine) in a three‐way, randomized, single‐blind Latin‐squares crossover study.

Results:

Using the FDA‐approved criterion for positive secretin testing (i.e. a serum gastrin concentration increase of > 110 pg/mL), there was complete agreement between all three agents for all patients. With the more stringent NIH criterion (i.e. a serum gastrin concentration increase of > 200 pg/mL), positive results persisted in five out of six, six out of six and four out of six patients using biologically‐derived secretin, synthetic porcine secretin, and synthetic human secretin, respectively (six out of six, six out of six and four out of six if a positive test was defined as a 50% increase in serum gastrin concentration). The time to peak serum gastrin concentration after secretin injection occurred within 15 min in all studies (in 94% by 10 min and in 77% by 5 min). Three‐way comparisons of serum gastrin concentrations showed a single statistically significant difference (the change from baseline at 15 min between synthetic human and synthetic porcine secretin, P=0.0274). Statistically significant changes from baseline occurred at 1, 2 and 5 min for biologically‐derived porcine secretin and at 2 and 5 min for both synthetic porcine and synthetic human secretin, in keeping with the expected time curve for positive tests. All three agents were well‐tolerated.

Conclusions:

These data suggest that either synthetic secretin product, when released onto the United States market, can be used to confirm Zollinger–Ellison Syndrome.
Bolus somatostatin but not octreotide reduces hepatic sinusoidal pressure by a NO‐independent mechanism in chronic liver disease
Authors: Matrella E. , Valatas V. , Notas G. , Roumpaki H. , Xidakis C. , Hadzidakis A. , Mouzas I. , Kouroumalis E.
Published: March 2003

Background:

Evidence exists that somatostatin and octreotide might have different effects on hepatic haemodynamics.

Aim:

The investigation of the effects of somatostatin and its octapeptide analogue, octreotide, on sinusoidal pressure measured by the wedged hepatic venous pressure in patients with cirrhosis or chronic hepatitis and the correlation with the levels of hepatic vein NO.

Methods:

Patients were randomly assigned to receive an injection of either 250 μg somatostatin (n=14: cirrhosis six, chronic hepatitis eight) or an injection of 125 μg octreotide (n=19: cirrhosis nine, chronic hepatitis 10) during hepatic vein catheterization. Baseline wedged hepatic venous pressure was measured, followed by measurements at 2, 5, 10 and 15 min after the injection of the drug. Nitrites/nitrates of the hepatic vein were measured before the injection and after 15 min.

Results:

Both agents showed a similar qualitative but a different quantitative haemodynamic profile. No change in the wedged hepatic venous pressure was observed during the first 2 min after the injection of both drugs. This was followed by a decrease: 18% at 5 min (N.S.), 23% at 10 min (P < 0.01) and 24% at 15 min (P < 0.01) for somatostatin. Octreotide induced a relatively smaller decrease in the wedged hepatic venous pressure: 8% at 5 min (N.S.), 20% at 10 min (P < 0.01) and 16% at 15 min (N.S.). Further analysis of the sub‐groups of cirrhotic and chronic hepatitis patients revealed a different effect. In the sub‐group of cirrhotic patients, somatostatin caused a maximum decrease of 34% at 15 min post‐injection (P < 0.01), but octreotide failed to produce a significant change on the wedged hepatic venous pressure. In contrast, no change was observed in chronic hepatitis patients with either drug. No change in the hepatic vein concentration of NO after treatment was observed with either somatostatin or octreotide. Moreover, no correlation of the levels of NO with the wedged hepatic venous pressure values was found.

Conclusions:

This study shows that somatostatin is more effective than octreotide in acutely reducing the wedged hepatic venous pressure after bolus injection and the observed change is probably mediated by a NO‐independent mechanism.
What is the optimal length of proton pump inhibitor‐based triple therapies for H. pylori? A cost‐effectiveness analysis
Authors: Calvet X. , Gené E. , LÓpez T. , Gisbert J. P.
Published: March 2003

Background:

Triple therapy with a proton pump inhibitor, clarithromycin and amoxicillin is widely used for H. pylori infection. The appropriate length of treatment remains controversial.

Aim:

To determine whether length of treatment has an impact on the cost‐effectiveness of triple therapy.

Methods:

The study took the form of a cost‐effectiveness analysis spanning 2 years. The perspective was societal and the setting, ambulatory care. Subjects were Helicobacter pylori‐positive patients with a duodenal ulcer. The triple therapy trials spanned 7, 10 or 14 days and the main outcome measures were cost per patient and marginal cost for additional cured patient calculated for a low cost‐of‐care setting (Spain), for a high‐cost setting (USA), and for two follow‐up strategies: (i) systematic 13C‐urea breath test after eradication; (ii) clinical follow‐up, breath‐test if symptoms recurred.

Results:

Base‐case analysis showed that for both the 13C‐UBT and the clinical follow‐up branches, lowest costs were obtained with 7‐day schedules both in Spain and the USA. Sensitivity analysis showed that in Spain, 10‐day therapies would have to increase 7‐day cure rates by 10–12% to become cost‐effective. In contrast, in the USA only a 3–5% increase was needed. The corresponding figures for 14‐day therapy were 25–35% and 8–11%, respectively.

Conclusions:

Seven‐day therapies seem the most cost‐effective strategy. However, in high‐cost areas the differences were less evident.
Influence of anti‐Helicobacter triple‐therapy with metronidazole, omeprazole and clarithromycin on intestinal microflora
Authors: Bühling A. , Radun D. , Müller W. A. , Malfertheiner P.
Published: March 2003

Background:

Proton pump inhibitor‐based therapy including two antibiotics is the treatment of choice for Helicobacter pylori infection. Oral antibiotic treatment can lead to intestinal overgrowth of potentially pathogenic bacteria.

Aim:

To investigate the intestinal microflora before and at different times after H. pylori treatment with omeprazole, clarithromycin and metronidazole.

Methods:

Bacterial growth in faecal samples from 51 patients infected with H. pylori was determined qualitatively and quantitatively. During the same period of time, stool samples from 27 H. pylori‐negative controls were taken and investigated at the same intervals.

Results:

The microflora of H. pylori‐infected patients was different from that in H. pylori negative controls. It was characterized by a high concentration of lactobacilli, mainly Lactobacillus acidophilus. Immediately after therapy there was an increased colonization with yeasts, while the growth of lactobacilli and other species was inhibited. Clostridium difficile was cultured from three cases, but without clinical manifestations of pseudomembranous colitis. After 4 weeks of therapy, the microflora returned to normal and was not different from that of the H. pylori‐negative control group.

Conclusions:

In H. pylori‐positive patients the intestinal flora is characterized by an increase in growth of acid‐tolerant L. acidophilus. Eradication therapy exerts only a short‐term influence on intestinal flora, whereas in the long term, the intestinal microflora is restored to a pattern similar to that of the control group.
A study of fructo oligosaccharides in the prevention of travellers’ diarrhoea
Authors: Cummings J. H. , Christie S. , Cole T. J.
Published: March 2003

Background

: Prebiotic carbohydrates selectively stimulate the growth of bifidobacteria and lactobacilli in the human colon. These bacteria form part of the gut’s inherent defence against invading pathogens.

Aim

: To test the effectiveness of fructo oligosaccharides in preventing travellers’ diarrhoea.

Methods

: A total of 244 healthy subjects, travelling to high and medium risk destinations for travellers’ diarrhoea, took part in a randomized, double‐blind, placebo‐controlled study. The protocol comprised a preliminary week for recording bowel habit by diary, a 2‐week pre‐holiday period with the diary and consumption of 10 g of fructo oligosaccharides or placebo daily, followed by a 2‐week holiday with continuation of treatment and diary. A post‐study questionnaire was completed by all subjects on their return to the UK.

Results

: The consumption of fructo oligosaccharides led to a small (6%; P < 0.02) increase in stool frequency in the pre‐holiday period and gave a significantly better sense of ‘well‐being’ during the holiday, although subjects reported more flatulence. There were non‐significant decreases in episodes of diarrhoea with 20% on placebo and 11% on fructo oligosaccharides recording episodes in the post‐study questionnaire (P=0.08) and 46% placebo, 38% fructo oligosaccharides recording episodes in the diary (P > 0.1). No change in bowel frequency, consistency or stool size was recorded.

Conclusion

: Travel to high risk areas increases diarrhoea. Fructo oligosaccharides alone are not sufficient to prevent this, although do have some benefits for the subjects.
Alternative antibacterial agents for Helicobacter pylori eradication
Authors: Guslandi M.
Published: March 2003

Standard eradication therapies against Helicobacter pylori appear to be effective in most cases, but in clinical practice a failure rate higher than the 5–10% reported in clinical trials is often observed. Among the various reasons responsible for therapeutic failure, antibiotic resistance is becoming a major issue in some countries. A range of different antibacterial agents is currently under investigation: several macrolides, new fluoroquinolones, furazolidone and rifabutin.

Although not formally tested in refractory cases, azithromycin, spiromycin, levofloxacin and furazolidone represent the most promising antibacterial agents for possible inclusion in eradication regimens.

Rifabutin has been evaluated in H. pylori infections resistant to standard therapies. Although very effective, the drug is expensive and its use should be restricted to the most difficult cases to avoid the development of rifabutin resistance in Mycobacterium spp.
Intragastric distribution of Helicobacter pylori during short‐term omeprazole therapy: study using Carnoy’s fixation and immunohistochemistry for detection of bacteria
Authors: Ishihara S. , Okuyama T. , Ishimura N. , Ono M. , Hashimoto T. , Kazumori H. , Kaji T. , Sato H. , Fujishiro H. , Adachi K. , Fukuda R. , Kinoshita Y.
Published: March 2003

Background:

There is controversy about the effect of acid‐suppressive therapy on Helicobacter pylori density and the severity of histological gastritis in the corpus.

Aim:

To evaluate the precise distribution of H. pylori, both on the surface mucus cells and in the surface mucus gel layer, by using Carnoy’s fixation and immunostaining for the detection of bacteria.

Methods:

A total of 19 peptic ulcer patients with H. pylori infection were studied. All patients received a 6‐week course of treatment with omeprazole (20 mg/day). Before and after the therapy, H. pylori density in Carnoy‐fixed tissue sections was examined immunohistochemically. The effect of omeprazole therapy on the severity of gastritis was also evaluated.

Results:

H. pylori density and the grade of gastritis significantly decreased in the antrum after omeprazole therapy. In the corpus, however, there were no significant changes in H. pylori density or the severity of gastritis after omeprazole therapy.

Conclusion:

Carnoy’s fixation and immunostaining was found to be useful for the detection of H. pylori in the surface mucus gel layer as well as on the surface mucus cells in biopsy tissue sections. By using this method, H. pylori density decreased in the antrum, but remained unchanged in the corpus after a 6‐week course of omeprazole therapy.
Influence of pantoprazole on oesophageal motility, and bile and acid reflux in patients with oesophagitis
Authors: Netzer P. , Gut A. , Brundler R. , Gaia C. , Halter F. , Inauen W.
Published: March 2003

Background:

Reflux of duodeno‐gastric juice into the oesophagus appears to be involved in the pathogenesis of both reflux oesophagitis and oesophageal adenocarcinoma. Although proton pump inhibitors have been shown to decrease acid reflux and heal oesophagitis, their effect on biliary reflux and motility is less clear.

Aim:

To investigate whether pantoprazole also reduces bile reflux and whether this is paralleled by a change in oesophageal motility.

Methods:

Combined 24‐h measurements of intraoesophageal bilirubin concentration, pH and pressure were performed in 18 symptomatic patients with endoscopically proven reflux oesophagitis before and on day 28 of treatment with pantoprazole, 40 mg/day, under standardized conditions. A reflux symptom score was determined initially and every 2 weeks thereafter. After 56 days on medication, a control endoscopy was performed.

Results:

The symptom score and the acid and bile reflux improved significantly, whereas the motility parameters did not change during the study period. Helicobacter pylori‐positive patients had a significantly higher bile reflux time (32.1 ± 4.3%) than H. pylori‐negative patients (16.3 ± 3.1%) (P=0.009). The endoscopic healing rate was 89%. The cough symptoms disappeared in three of four patients.

Conclusions:

The proton pump inhibitor pantoprazole decreases both acid and bile reflux. The decrease of bile reflux cannot be explained by increased oesophageal clearance as oesophageal motility did not improve with therapy. Interestingly, H. pylori infection of the stomach was associated with higher levels of oesophageal bile reflux.
Octreotide increases the proportions of arachidonic acid‐rich phospholipids in gall‐bladder bile
Authors: Pereira S. P. , Hussaini S. H. , Murphy G. M. , Wass J. A. H. , Dowling R. H.
Published: March 2003

Background and aims:

Octreotide treatment of acromegalic patients induces cholesterol gallstone formation, in part by impairing cholecystokinin release and gall‐bladder contraction. However, there are few data on the effect of octreotide on biliary arachidonic acid‐rich phospholipids or mucin glycoprotein, factors which also influence cholesterol gallstone formation.

Methods:

In acromegalic patients studied before and during 3 months of octreotide treatment, we measured mucin glycoprotein concentrations and the molecular species of phosphatidylcholine, and related the results to the cholesterol saturation and percentage of deoxycholic acid in gall‐bladder bile.

Results:

The relative proportions of the major arachidonic acid‐rich phosphatidylcholine species, PC 16:0–20:4 and PC 18:0–20:4, increased significantly during octreotide treatment. These changes were associated with a rise in the cholesterol saturation index and a non‐significant twofold increase in mucin glycoprotein concentration. There were significant correlations between PC 16:0–20:4 and the cholesterol saturation index, percentage of vesicular cholesterol and percentage of deoxycholic acid in gall‐bladder bile.

Conclusions:

In acromegalic patients, octreotide increases the proportions of arachidonic acid‐rich phospholipids, with associated rises in: (a) the cholesterol saturation index and percentage of vesicular cholesterol, and (b) the percentage of deoxycholic acid in gall‐bladder bile—changes similar to those found in patients with cholesterol‐rich gall‐bladder stones.
Comparable clinical efficacy and tolerability of 20 mg pantoprazole and 20 mg omeprazole in patients with grade I reflux oesophagitis
Authors: Bardhan K. D. , Van Rensburg C. ,   (on behalf of the investigators)
Published: March 2003

Background:

Several clinical trials have shown that pantoprazole (40 mg) and omeprazole (40 or 20 mg) have similar efficacy and safety in the treatment of grade II–IV reflux oesophagitis (Savary–Miller classification).

Aim:

To compare the efficacy and safety of once‐daily doses of pantoprazole (20 mg) and omeprazole (20 mg) with respect to symptom relief and healing of patients with grade I reflux oesophagitis.

Methods:

Patients with endoscopically established grade I reflux oesophagitis (non‐confluent, patchy red lesions with/without white fibrin coating) were enrolled into this randomized, open, parallel‐group, multicentre study. A total of 328 patients (n=166 in the pantoprazole group, n=162 in the omeprazole group) were recruited in 23 centres. Patients received 4 weeks of treatment. If the reflux oesophagitis was not completely healed, the treatment was extended to 8 weeks.

Results:

After 2 and 4 weeks of treatment with either pantoprazole or omeprazole, the rate of symptom relief was similar (70% vs. 79% and 77% vs. 84%, respectively). High healing rates were observed after 4 and 8 weeks (pantoprazole: 84% and 90%, respectively; omeprazole: 89% and 95%, respectively). Both treatments were well tolerated. The most frequently reported adverse events on pantoprazole and omeprazole, respectively, were nausea (8% vs. 7%), diarrhoea (5% vs. 6%) and headache (6% vs. 3%).

Conclusions:

After 4 and 8 weeks of treatment with pantoprazole (20 mg) or omeprazole (20 mg), patients with mild gastro‐oesophageal reflux disease (grade I) showed comparably high rates of symptom relief and healing. Both treatments were safe and well tolerated.
Clinical use of Infliximab in Crohn’s disease: the Edinburgh experience
Authors: Arnott I. D. R. , McDonald D. , Williams A. , Ghosh S.
Published: March 2003

Introduction:

Infliximab is an established treatment for steroid‐resistant and fistulating Crohn’s disease. Although efficacy has been shown in clinical trials, financial implications often limit its use and limited data exist regarding clinical practice.

Aims:

To audit the clinical effectiveness of Infliximab.

Methods:

We prospectively audited 50 consecutive patients [28 females; median age, 34 years (17–70 years)]. Disease activity and response rates were assessed by the Harvey–Bradshaw index. Clinical and disease data were collected and blood was taken for inflammatory markers, complement and double‐stranded DNA antibodies. Patients received Infliximab at 5 mg/kg and were followed for 12 weeks.

Results:

Indications for Infliximab were refractory Crohn’s disease in 39 patients, fistulating Crohn’s disease in six, pyoderma gangrenosum in one, pouchitis in two and coeliac disease in two. Thirty‐one (79%) of the refractory Crohn’s disease patients and four (66%) of the fistulating patients responded at 4 weeks. Twenty‐one (54%) of the refractory Crohn’s disease patients had a continued response at 12 weeks. Perianal disease was more prevalent in non‐responders (7/8 vs. 12/31, P < 0.02).

Conclusions:

Response rates to Infliximab in our group are comparable to those of clinical trials. Despite the expense, it remains a useful adjunct to treatment in this otherwise difficult group of patients. Patients with perianal disease responded less well in our cohort.
Efficacy and safety of oral ridogrel in the treatment of ulcerative colitis: two multicentre, randomized, double‐blind studies
Authors: Tytgat G. N. J. , Van Nueten L. , Van De Velde I. , Joslyn A. , Hanauer S. B.
Published: March 2003

Background:

Ridogrel at low doses inhibits thromboxane synthase. Oral ridogrel, from 5 mg once daily to 150 mg twice daily, improves the endoscopic appearance of colonic mucosa and clinical manifestations in mild to moderate ulcerative colitis.

Aim:

One US trial and one international trial were conducted to determine the effect of ridogrel on mild to severe active ulcerative colitis.

Methods:

Two 12‐week, double‐blind, randomized, parallel‐group trials were conducted. A US trial compared 0.5 mg, 2.5 mg and 5 mg of ridogrel once daily with placebo. An international trial compared 0.5 mg of ridogrel once daily with 2.5 mg and 5.0 mg of ridogrel once daily and 800 mg of mesalazine (known as mesalamine in the USA) three times daily. The primary efficacy outcome measure was the rate of complete remission.

Results:

In the US trial, complete remission was achieved in 20.8% of patients in the 0.5 mg ridogrel group, 17.9% in the 2.5 mg ridogrel group, 20.6% in the 5.0 mg ridogrel group and 13.6% in the placebo group. In the international trial, 14.4% of patients in the 0.5 mg ridogrel group, 19.6% in the 2.5 mg ridogrel group, 19.4% in the 5.0 mg ridogrel group and 16.4% in the mesalazine group experienced complete remission. In the international trial, rates of complete remission at the end‐point were greater in the 2.5 mg and 5.0 mg ridogrel groups than in the 0.5 mg ridogrel group, but the differences were not statistically significant. In the US trial, rates of complete remission at the end‐point were greater in the 2.5 mg and 5.0 mg ridogrel groups than in the placebo group, but the differences were not statistically significant. Approximately 30% of the patients in each group discontinued treatment before the 12‐week end‐point owing to a lack of therapeutic response. All doses of ridogrel were well tolerated and comparable with placebo or mesalazine in terms of safety.

Conclusions:

No significant differences in the primary efficacy outcome measure were found between either the 2.5 mg or the 5.0 mg dose of ridogrel and placebo in the US trial and between either the 2.5 mg or the 5.0 mg dose of ridogrel and the 0.5 mg dose of ridogrel, a surrogate dose for placebo, in the international trial. There was no clear indication in either trial of an effective dose of ridogrel in the treatment of ulcerative colitis.
High rate of post‐therapeutic resistance after failure of macrolide–nitroimidazole triple therapy to cure Helicobacter pylori infection: impact of two second‐line therapies in a randomized study
Authors: Peitz U. , Sulliga M. , Wolle K. , Leodolter A. , Von Arnim U. , Kahl S. , Stolte M. , Börsch G. , Labenz J. , Malfertheiner P.
Published: March 2003

Background:

The optimal second‐line treatment after failed Helicobacter pylori therapy has not been established.

Aims:

To ascertain whether quadruple therapy or triple therapy with omeprazole, clarithromycin and amoxicillin is the superior re‐treatment after triple therapy containing a macrolide and a nitroimidazole, and to determine the impact of microbial in vitro resistance.

Methods:

Patients after failed triple therapy were randomly allocated to one of two 1‐week second‐line treatments: omeprazole, 40 mg, clarithromycin, 500 mg, and amoxicillin, 1 g, all b.d.; or omeprazole, 20 mg b.d., bismuth subsalicylate, 600 mg q.d.s., metronidazole, 400 mg t.d.s., and tetracycline, 500 mg q.d.s. Post‐therapeutic Helicobacter pylori status was assessed by 13C‐urea breath test at least 4 weeks after treatment.

Results:

The study was terminated after including 84 patients. H. pylori cure rates differed significantly: omeprazole–clarithromycin–amoxicillin: intention‐to‐treat, 43%; per protocol, 50%; omeprazole–bismuth subsalicylate–metronidazole–tetracycline: intention‐to‐treat, 68%; per protocol, 69%. The frequencies of resistance after first‐line therapy were: metronidazole, 90%; clarithromycin, 71%; both combined, 68%. For clarithromycin resistance, H. pylori cure with omeprazole–clarithromycin–amoxicillin was 30% vs. 83% for clarithromycin susceptibility.

Conclusions:

Omeprazole–bismuth subsalicylate–metron‐ idazole–tetracycline was superior to omeprazole–clarithromycin–amoxicillin, but both therapies yielded unsatisfactory results. The high rate of post‐therapeutic dual resistance has a negative impact on omepraz‐ ole–clarithromycin–amoxicillin, and probably also on omeprazole–bismuth subsalicylate–metronidazole–tetracycline, and limits the choice for second‐line treatment.
13C‐Aminopyrine breath test to evaluate severity of disease in patients with chronic hepatitis C virus infection
Authors: Giannini E. , Fasoli A. , Chiarbonello B. , Malfatti F. , Romagnoli P. , Botta F. , Testa E. , Polegato S. , Fumagalli A. , Testa R.
Published: March 2003

Background:

There are few data on the use of the 13C‐aminopyrine breath test to evaluate the severity of disease in patients with hepatitis C virus‐related chronic liver disease, although these patients represent one of the most important problems in clinical hepatology.

Aims:

To compare 13C‐aminopyrine breath test results of patients with hepatitis C virus‐related chronic hepatitis and Child–Pugh class A cirrhosis with those of normal subjects, and to evaluate different methods of expressing 13C‐aminopyrine breath test results.

Methods:

Twenty‐four patients with hepatitis C virus‐related chronic hepatitis and 17 patients with Child–Pugh class A cirrhosis underwent 13C‐aminopyrine breath test. Breath samples were collected every 30 min up to 2 h after 13C‐aminopyrine administration. 13C‐Aminopyrine breath test results were expressed as a percentage of the administered dose of 13C recovered per hour (% dose/h) and the cumulative percentage of administered dose of 13C recovered over time (% dose cum). Nineteen healthy subjects served as controls. Patients with hepatitis C virus‐related chronic hepatitis were divided into subgroups on the basis of histological staging and grading.

Results:

The 13C‐aminopyrine breath test result (% dose/h) at 30 min was significantly different among the three subgroups of subjects (normal subjects, 11.5 ± 3.5; chronic hepatitis patients, 8.1 ± 4.1; cirrhosis patients, 5.0 ± 3.1; P < 0.0005). Moreover, the differences between chronic hepatitis and cirrhosis patients were statistically significant (P < 0.03). The fibrosis score showed a significant inverse correlation with the 13C‐aminopyrine breath test result (% dose/h) at 30 min (rs=− 0.409, P=0.05). The 13C‐aminopyrine breath test result (% dose/h) at 30 min also allowed normal subjects and chronic hepatitis patients with low (≤ 2) or high (> 2) fibrosis scores to be distinguished. The 13C‐aminopyrine breath test results (% dose cum) at 30, 60 and 90 min allowed discrimination between normal subjects and chronic hepatitis and cirrhosis patients. The 13C‐aminopyrine breath test result (% dose cum) was also able to distinguish between normal subjects and chronic hepatitis patients with high but not low fibrosis scores. Both 13C‐aminopyrine breath test results (% dose/h and % dose cum) at 120 min allowed the differentiation between normal subjects and chronic hepatitis patients with high (≥ 6) necro‐inflammatory activity.

Conclusions:

In patients with hepatitis C virus‐related chronic liver disease, the 13C‐aminopyrine breath test proved to be safe and easy to perform, and was able to evaluate different degrees of liver function impairment which were partly correlated to clinical and histological evaluation. In future studies, 13C‐aminopyrine breath test results should be expressed in a standardized fashion to permit comparison.
A pilot study of treatment of active ulcerative colitis with natalizumab, a humanized monoclonal antibody to alpha‐4 integrin
Authors: Gordon F. H. , Hamilton M. I. , Donoghue S. , Greenlees C. , Palmer T. , Rowley‐Jones D. , Dhillon A. P. , Amlot P. L. , Pounder R. E.
Published: March 2003

Background:

Alpha‐4 integrins facilitate leucocyte migration across vascular endothelium.

Aim:

To assess the safety and efficacy of natalizumab (Antegren), a humanized antibody to alpha‐4 integrin, in patients with active ulcerative colitis.

Methods:

Ten patients with active ulcerative colitis, defined by a Powell‐Tuck activity score > 4, received a single 3 mg/kg natalizumab infusion. The primary end‐point was the change in Powell‐Tuck score at 2 weeks post‐infusion.

Results

Significant decreases in the median Powell‐Tuck score were observed at 2 and 4 weeks post‐infusion (7.5 and 6, respectively) compared to the median baseline score (10). Five of 10 patients achieved a good clinical response at 2 weeks and one more patient by 4 weeks, defined by a Powell‐Tuck score of ≤ 5. Significant improvements in quality of life scores were found at week 4. Rescue medication was required by two (20%), three (30%) and eight (80%) patients by weeks 2, 4 and 8, respectively (median, 34 days; range, 8–43 days). One patient remained in remission at 12 weeks. The median C‐reactive protein at 2 weeks (6 mg/L) was lower than that pre‐treatment (16 mg/L).

Conclusions:

A single 3 mg/kg infusion of natalizumab was well tolerated by ulcerative colitis patients. The positive efficacy demonstrated in this study merits further investigation by randomized, placebo‐controlled trials.
The 13C‐urea breath test to detect Helicobacter pylori infection: a validated simple methodology with 50 mg 13C‐urea
Authors: Liao C.‐C. , Lee C.‐L. , Chiang T.‐C. , Lee S.‐C. , Huang S.‐H. , Tu T.‐C. , Chen T.‐K. , Wu C.‐H.
Published: March 2003

Background:

Several modifications of the 13C‐urea breath test have been published. For reasons of cost efficiency and practicability, the urea dose and measurement duration should be reduced while still maintaining excellent diagnostic accuracy.

Aims:

To establish a validated simple protocol for the urea breath test with 50 mg 13C‐urea and to compare this protocol with the conventional urea breath test with 100 mg 13C‐urea.

Methods:

Conventional urea breath test with 100 mg 13C‐urea was performed on 152 dyspeptic patients. Full‐cream cow's milk was used as the test meal. Breath tests were repeated using 50 mg 13C‐urea and the breath samples were collected at baseline and at 10 (protocol t10), 15 (protocol t15) and 30 min (protocol t30). Helicobacter pylori status was assessed by rapid urease test, histology and conventional urea breath test with 100 mg 13C‐urea.

Results:

With protocol t15, the best combination of sensitivity (99.1%), specificity (97.3%) and accuracy (98.7%) was obtained with a cut‐off of 2.5‰. There was an extremely high correlation coefficient between the three protocols and conventional 13C‐urea breath test (all P < 0.001).

Conclusions:

A urea breath test with 50 mg 13C‐urea using a simple test meal and a 15‐min sampling interval with a low cut‐off seems to be cost‐effective and convenient. In a well‐standardized laboratory, this modification is not associated with any loss of diagnostic accuracy.
Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low‐dose aspirin
Authors: Lanas A. , Fuentes J. , Benito R. , Serrano P. , Bajador E. , Sáinz R.
Published: March 2003

Aim:

To evaluate the role of Helicobacter pylori infection and other clinical factors in the risk of upper gastrointestinal bleeding in patients taking low‐dose aspirin.

Subjects and methods:

A case–control study was carried out of consecutive current users of low‐dose aspirin admitted because of upper gastrointestinal bleeding. Within a cohort of 695 patients with upper gastrointestinal bleeding, 98 patients had taken low‐dose aspirin and no other non‐steroidal anti‐inflammatory drug. Controls were 147 low‐dose aspirin users without upper gastrointestinal bleeding of similar age, sex and extent of aspirin use as cases. H. pylori infection was determined by CagA/VacA serology and 13C‐urea breath test in all cases and controls. Adjusted odds ratios (OR) are provided.

Results:

H. pylori infection was identified as an independent risk factor of upper gastrointestinal bleeding in this population (OR, 4.7; 95% confidence interval (95% CI), 2.0–10.9), but the presence of CagA‐positive serology was not. Other risk factors identified were a previous ulcer history (OR, 15.2; 95% CI, 3.8–60.1), alcohol use (OR, 4.2; 95% CI, 1.7–10.4) and use of calcium channel blockers (OR, 2.54; 95% CI, 1.25–5.14). Antisecretory therapy (OR, 0.1; 95% CI, 0.02–0.3) and nitrovasodilators (OR, 0.2; 95% CI, 0.1–0.6) decreased the risk of bleeding.

Conclusions:

H. pylori infection is a risk factor for upper gastrointestinal bleeding in low‐dose aspirin users, which might have therapeutic implications in high‐risk patients.
P‐Glycoprotein‐170 inhibition significantly reduces cortisol and ciclosporin efflux from human intestinal epithelial cells and T lymphocytes
Authors: Farrell R. J. , Menconi M. J. , Keates A. C. , Kelly C. P.
Published: March 2003

Aim:

To assess the role of P‐glycoprotein‐170 (P‐gp) in transporting cortisol and ciclosporin from human intestinal epithelium and T lymphocytes.

Methods:

The effect of P‐gp inhibitors (verapamil, 0–100 μM; PSC 833, 0–20 μM) on the intracellular accumulation of 3H‐cortisol and 3H‐ciclosporin was studied in confluent layers of human Caco‐2 cells (n=6), a P‐gp‐dependent absorptive intestinal epithelial cell phenotype, and moderately resistant MDRhigh CEM/VBL 100 T cells (n=6). The transport of 3H‐vinblastine, a strong multidrug resistance (MDR) substrate, and 3H‐progesterone, a poor MDR substrate, was also studied.

Results:

Caco‐2 cells had a 2.4‐, 6.6‐, 6.7‐ and 1.03‐fold higher net basal to apical transport (efflux) of 3H‐cortisol, 3H‐ciclosporin, 3H‐vinblastine and 3H‐progesterone, respectively. PSC 833 (20 μM) reduced cortisol efflux by 69% (0.23 ± 0.04 to 0.07 ± 0.01 pmol/cm2/h, P < 0.05) and ciclosporin efflux by 76% (11.1 ± 1.4 to 2.7 ± 0.6 pmol/cm2/h, P < 0.001). MDRlow CEM T cells had a 1.4‐, 1.9‐, 3.2‐ and 1.02‐fold higher intracellular accumulation of cortisol, ciclosporin, vinblastine and progesterone than MDRhigh CEM/VBL 100 T cells. Increasing concentrations of PSC 833 (> 0.1 μM) and verapamil (> 1 μM) restored the intracellular level of 3H‐cortisol and 3H‐ciclosporin in MDRhigh CEM/VBL 100 T cells to that of MDRlow CEM cells with little change in accumulation in the MDRlow parental cell line.

Conclusions:

P‐gp inhibitors significantly increase intracellular cortisol and ciclosporin levels in human intestinal epithelium and T lymphocytes in a dose‐dependent manner, demonstrating a potential mechanism for overcoming poor response to immunosuppressant therapy in refractory inflammatory bowel disease.
Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta‐analysis
Authors: Vallve M. , Vergara M. , Gisbert J. P. , Calvet X.
Published: March 2003

Background:

Triple therapies combining a double dose of proton pump inhibitor plus two antibiotics are the standard treatment for Helicobacter pylori infection. Some reports suggest that the use of half the dose of proton pump inhibitor is equally effective.

Aim:

To compare the efficacy of a single vs. double dose of proton pump inhibitor in triple therapy.

Methods:

We conducted a MEDLINE search. The search strategy included the words (pylori) AND (triple, PPI, proton pump, omeprazole, rabeprazole, pantoprazole, lansoprazole, clarithromycin, amoxicillin, amoxycillin or metronidazole). Abstracts of the articles obtained and papers presented at the European Helicobacter pylori Study Group and American Gastroenterological Association congresses from 1996 to 2001 were examined. Inclusion criteria were: (i) randomized studies with at least two branches of triple therapy including a proton pump inhibitor and two standard antibiotics; (ii) branches could differ only in terms of proton pump inhibitor dosage. A meta‐analysis was conducted using conventional shareware (Review Manager 4.1).

Results:

Thirteen studies met the inclusion criteria with a total of 2391 patients. Cure rates with double doses of proton pump inhibitor were higher in both the intention‐to‐treat analysis (83.9% vs. 77.7%; Peto odds ratio, 1.51; 95% confidence interval, 1.23–1.85; P < 0.01) and per protocol analysis (89% vs. 81%; Peto odds ratio, 1.96; 95% confidence interval, 1.55–2.47; P < 0.01).

Conclusion:

Triple therapies containing a single dose of proton pump inhibitor are less effective than those containing a standard double dose of proton pump inhibitor.
An open‐label study of thalidomide for maintenance therapy in responders to infliximab in chronically active and fistulizing refractory Crohn's disease
Authors: Sabate J. M. , Villarejo J. , Lemann M. , Bonnet J. , Allez M. , Modigliani R.
Published: March 2003

Background : Infliximab, a chimeric monoclonal antibody to tumour necrosis factor‐α, is a new potent therapy for active Crohn's disease, but induces short‐lived improvements.

Aim : To evaluate the efficacy of thalidomide, a drug with anti‐tumour necrosis factor‐α activity, for the maintenance of infliximab‐induced response in refractory Crohn's disease.

Methods : Fifteen patients with severe, refractory disease (10 females, five males; mean age, 40 years; eight with luminal disease, two with fistulizing disease and five with both luminal and fistulizing disease) were started on thalidomide (100 mg daily), 29 ± 10 days after they had responded to infliximab (5 mg/kg infusions).

Results : The median follow‐up period was 238 days (range, 10–458 days) from the initiation of thalidomide and 265 days (range, 10–537 days) from the last infliximab infusion. The median Crohn's disease activity indices were 322 (range, 170–525), 119 (range, 24–503) and 35 (range, − 60–360) before infliximab, at the initiation of thalidomide and at the end of follow‐up, respectively. Remission rates on thalidomide were 92%, 83% and 83% at 3, 6 and 12 months, respectively, after the last infliximab infusion (Kaplan–Meier). Four patients (two in remission) stopped thalidomide for suspected adverse effects. Side‐effects (drowsiness, rash and peripheral neuropathy) were mild and mostly transient.

Conclusions : Thalidomide appears to be an effective and relatively safe drug to maintain response to infliximab in chronically active and fistulizing refractory Crohn's disease.