bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of proton pump inhibitors in non‐H. pylori‐related ulcers
Authors: Freston J.W.
Published: March 2003

The proportion of ulcers that are not associated with Helicobacter pylori infection is increasing, especially in the United States and Australia. The alarming increase in this type of ulcer warrants an analysis of the diagnostic and treatment approaches to H. pylori‐negative ulcers, which was the aim of this study. The medical literature was reviewed to gather information about the prevalence, aetiology, and treatment of H. pylori‐negative ulcers. The reports indicated that up to 52% of duodenal ulcers and 47% of gastric ulcers are not caused by H. pylori infection. The cause of H. pylori‐negative ulceration appears to be multifactorial. Contributing factors include covert non‐steroidal anti‐inflammatory drug use, false‐negative H. pylori tests, genetic predisposition, and in rare cases, Crohn’s disease or Zollinger–Ellison syndrome. H. pylori‐negative ulcers tend to be associated with hypersecretion and can have serious clinical sequelae. H. pylori‐negative ulcers are often refractory to treatment, possibly because they lack the beneficial effect of H. pylori infection on antisecretory therapy. Proton pump inhibitors (PPIs) appear to effectively treat both H. pylori‐positive and H. pylori‐negative ulcers. We conclude that H. pylori‐negative ulcers are becoming more prevalent in the United States and Australia. These ulcers may have an aggressive clinical course and can be refractory to treatment. PPI therapy is indicated for treating and preventing H. pylori‐negative peptic ulcers.
Tegaserod
Authors: Camilleri M.
Published: March 2003

Tegaserod (Zelmac), an aminoguanidine indole derivative of serotonin, is a selective partial agonist highly selective for 5‐HT4 receptor with an affinity constant in the nanomolar range. Tegaserod does not cause adverse pharmacodynamic effects, is absorbed rapidly after oral administration and distributes widely into tissues. Pharmacokinetics of oral tegaserod are linear in the 2–12 mg dose range. After oral administration tegaserod is metabolized mainly pre‐systemically; when absorbed, intact tegaserod is excreted as N‐glucuronides mainly via the bile. No clinically relevant drug–drug interactions were identified. Tegaserod has proven safe in toxicity studies.

In pharmacodynamic studies, tegaserod stimulated the peristaltic reflex in vitro, increased canine intestinal and colonic motility and transit, reduced visceral afferent firing or sensation in response to distension in animals, and accelerated gastric, small bowel and colonic transit in healthy patients, and small bowel transit in patients with constipation‐predominant irritable bowel syndrome.

Three large phase III randomized, double‐blinded, and placebo‐controlled trials were performed predominantly in females (≈ 85%) with constipation‐predominant irritable bowel syndrome. Overall, phase III results support efficacy as assessed by the subject’s global assessment of relief with significant improvement in secondary endpoints such as abdominal pain, bowel frequency and consistency. Tegaserod was well‐tolerated; the most frequent adverse event was transient diarrhoea.
Three‐day lansoprazole quadruple therapy for Helicobacter pylori‐positive duodenal ulcers: a randomized controlled study
Authors: Wong B. C. Y. , Wang W. H. , Wong W. M. , Lau G. K. K. , Fung F. M. Y. , Kung N. N. S. , Chu K. M. , Lai K. C. , Hu W. H. C. , Hu F. L. , Liu X. G. , Chan C. K. , Yuen M. F. , Hui W. M. , Lam S. K.
Published: March 2003

Aim:

To compare the efficacy and tolerability of a 3‐day quadruple therapy with a standard 7‐day triple therapy in eradicating Helicobacter pylori infection and healing duodenal ulcers.

Methods:

Patients with H. pylori‐positive duodenal ulcers were randomized to receive either lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 400 mg twice daily for 7 days (LCM‐7) or lansoprazole 30 mg, clarithromycin 500 mg, metronidazole 400 mg, and bismuth subcitrate 240 mg twice daily for 3 days (LCMB‐3). No pre‐ or post‐treatment acid suppression was used. Follow‐up endoscopy was performed at week 6.

Results:

A total of 118 patients were recruited. Sixty patients in the LCM‐7 group and 53 patients in the LCMB‐3 group returned for endoscopy. Intention‐to‐treat eradication rates were 87% and 86% (P=0.94) and per protocol eradication rates were 87% and 94% (P=0.29) in the LCM‐7 and LCMB‐3 groups, respectively. Per protocol and intention‐to‐treat ulcer healing rates were 98% and 98% in LCM‐7 and 100% and 91% in LCMB‐3, respectively. There were no significant differences in efficacy in relation to the initial metronidazole and clarithromycin susceptibility. Significant reduction in the duration of side‐effects was found in the LCMB‐3 group.

Conclusion:

The 3‐day quadruple therapy is highly effective, better tolerated and can be considered as a first‐line therapy in duodenal ulcer management.
Ambulatory gastric pH monitoring: proper probe placement and normal values
Authors: Fackler W. K. , Vaezi M. F. , Richter J. E.
Published: March 2003

Background

: Gastric acid production may persist while patients are treated with proton pump inhibitors. Twenty‐four‐hour intragastric pH monitoring is being used to identify gastric acid in the stomach while on medical therapy.

Aim

: To identify the optimal region of the stomach to demonstrate the presence of gastric acid.

Method

: Probe locations confirmed with fluoroscopy after placement and prior to removal. In experiment 1, five volunteers underwent simultaneous, 24‐h gastro‐oesophageal pH monitoring with the pH sensors located in the gastric antrum, body, fundus and distal oesophagus. In experiment 2, five volunteers underwent simultaneous 24‐h pH monitoring with sensors located side by side in the gastric fundus assessing the reproducibility of gastric pH in this region. In experiment 3, 35 volunteers underwent 24‐h pH monitoring with pH sensors located in the distal oesophagus and gastric fundus. The mean percentage time for which pH < 4 was calculated for total, upright, and supine time periods. Results: pH profiles for the gastric fundus and body are similar—the mean percentage total time for which pH < 4 was 92.2% and 90.1%, respectively (P=N.S.). These values are significantly different from the antrum; pH < 4=54.6% (P < 0.01). pH values from the gastric fundus are highly reproducible (linear regression P= 0.004, r2=0.96). The normal values (mean ± 95th percentile) for percentage time gastric pH < 4 in the fundus were: total 95.6 ± 1.5%, upright 94.8 ± 1.8%, and supine 96.5 ± 2.3%.

Conclusion

: The fundus is the optimal location to evaluate the presence of gastric acid; pH values are highly reproducible in this area. Normal values for percentage time gastric pH < 4 for a healthy population are now defined.
Duodenogastric reflux following cholecystectomy in the dog: role of antroduodenal motor function
Authors: Nogi K. , Haruma K. , Taniguchi H. , Yomota E. , Okajima M. , Hananoki M. , Hata J. , Kusunoki H. , Onoda Y.
Published: March 2003

Background

: Duodenogastric reflux has been implicated in the pathogenesis of gastric ulcer and gastritis. Duodenogastric reflux after cholecystectomy is also a possible cause of post‐cholecystectomy syndrome.

Aim

: To investigate the role of antroduodenal motor function in increased duodenogastric reflux following cholecystectomy and the effect of trimebutine maleate (trimebutine) on the duodenogastric reflux in conscious dogs.

Methods

: Antropyloric and duodenal motility and bile acids content in the gastric juice were measured for 3 h during the inter‐digestive state in dogs with or without cholecystectomy.

Results

: Bile acids content in the gastric juice of cholecystectomized dogs was significantly higher than that of non‐cholecystectomized dogs. The frequency of pyloric relaxation during phase II of the migrating motor complex was significantly increased following cholecystectomy. Intravenous infusion of trimebutine inhibited both the increased duodenogastric reflux and the frequency of pyloric relaxation in the cholecystectomized dog.

Conclusion

: Duodenogastric reflux and frequency of pyloric relaxations were increased in cholecystectomized dogs and trimebutine suppressed both of them. These findings suggest that the increased frequency of pyloric relaxation contributes to the duodenogastric reflux following cholecystectomy.
Anal sphincter biofeedback and pelvic floor exercises for faecal incontinence in adults—a systematic review
Authors: Norton C. , Kamm M. A.
Published: March 2003

Background

: Faecal incontinence is a common health care problem. Biofeedback is extensively used in clinical practice to treat faecal incontinence.

Aim

: To systematically review and evaluate the evidence from clinical studies on the effectiveness of biofeedback as a treatment for faecal incontinence in adults.

Methods

: A systematic literature search was undertaken using electronic databases, with review of the retrieved references.

Results

: The search identified 46 studies published in English using biofeedback to treat adults complaining of faecal incontinence. Those studies included a total of 1364 patients. Of those studies with adequate data, 275 out of 566 patients (49%) were said to be cured of symptoms of faecal incontinence following biofeedback therapy and 617 out of 861 (72%) patients were reported to be cured or improved. Studies varied in the method of biofeedback used, criteria for success and the outcome measures used. Only eight of the 46 studies employed any form of control group.

Conclusions

: The data suggest that biofeedback and exercises help a majority of patients with faecal incontinence. However, methodological variation, lack of controls and a lack of validated outcome measures are problems in evaluating these results.
Review article: pathogenesis of Helicobacter pylori‐induced gastric inflammation
Authors: Israel D. A. , Peek R. M.
Published: March 2003

Helicobacter pylori causes persistent inflammation in the human stomach, yet only a minority of persons harbouring this organism develop peptic ulcer disease or gastric malignancy. An important question is why such variation exists among colonized individuals. Recent evidence has demonstrated that H. pylori isolates possess substantial phenotypic and genotypic diversity, which may engender differential host inflammatory responses that influence clinical outcome. For example, H. pylori strains that possess the cag pathogenicity island induce more severe gastritis and augment the risk for developing peptic ulcer disease and distal gastric cancer. An alternative, but not exclusive, hypothesis is that enhanced inflammation and injury is a consequence of an inappropriate host immune response to the chronic presence of H. pylori within the gastric niche. Investigations that precisely delineate the mechanisms responsible for induction of gastritis will ultimately help to define which H. pylori‐colonized persons bear the highest risk for subsequent development of clinical disease, and thus, enable physicians to focus eradication therapy.
Randomized controlled trial comparing botulinum toxin injection to pneumatic dilatation for the treatment of achalasia
Authors: Mikaeli J. , Fazel A. , Montazeri G. , Yaghoobi M. , Malekzadeh R.
Published: March 2003

Background:

Therapeutic options for achalasia include pharmacological therapy, surgical myotomy, pneumatic dilatation and intrasphincteric botulinum toxin injection.

Aim:

To compare botulinum toxin injection with pneumatic dilatation in a randomized trial.

Patients/methods:

Forty adults with newly diagnosed achalasia were randomized to receive botulinum toxin (n=20) or pneumatic dilatation (n=20). Symptom scores were evaluated at 1, 6 and 12 months. Clinical relapse was defined as a symptom score greater than 50% of baseline. Relapsers received a second botulinum toxin injection or pneumatic dilatation.

Results:

The cumulative 12‐month remission rate was significantly higher after a single pneumatic dilatation (53%) compared to a single botulinum toxin injection (15%)(P < 0.01). The 12‐month estimated adjusted hazard for relapse and need for retreatment for the botulinum toxin group was 2.69 times that of the pneumatic dilatation group (95% confidence interval; 1.18–6.14). When a second treatment was administered to the relapsers in each group, the cumulative remission rate 1 year after initial treatment was significantly higher in the pneumatic dilatation group (100%) compared to the botulinum toxin group (60%) (P < 0.01). There were no major complications in either group.

Conclusions:

Pneumatic dilatation is more efficacious than botulinum toxin in providing sustained symptomatic relief in patients with achalasia. The efficacy of a single pneumatic dilatation is similar to that of two botulinum toxin injections.
Inhibition of human colon cancer cell growth by antisense oligodeoxynucleotides targeted at basic fibroblast growth factor
Authors: Netzer P. , Domek M. , Pai R. , Halter F. , Tarnawski A.
Published: March 2003

Background:

Basic fibroblast growth factor has been shown to be mitogenic in colon cancer cell lines. In human malignant melanoma cells, antisense oligodeoxynucleotides targeted against basic fibroblast growth factor messenger RNA significantly inhibit cell growth. However, the efficacy of such an antisense oligodeoxynucleotide strategy has not been evaluated for colon cancer cells.

Aim:

To investigate whether basic fibroblast growth factor can stimulate the growth of HT‐29 human colon cancer cells and whether antisense oligodeoxynucleotides can inhibit growth of these cells at baseline.

Methods:

Western blotting analyses were used to confirm the presence of basic fibroblast growth factor protein in this cell line. Cell growth was assessed after 2, 4 and 6 days of treatment by cell counting using the trypan blue exclusion method. Phosphorothioate‐ modified oligodeoxynucleotides (10 μM) were used, complementary to codon 60 of the basic fibroblast growth factor messenger RNA. Cationic liposomes (DOTAP) were used to enhance the cellular uptake of the oligodeoxynucleotides.

Results:

Western blotting demonstrated the presence of basic fibroblast growth factor protein in this cell line. Basic fibroblast growth factor (1–40 ng/mL) dose‐dependently stimulated cell growth and peak values were obtained at a dose of 20 ng/mL. By contrast, antisense oligodeoxynucleotide treatment significantly inhibited cell growth compared with the sense oligodeoxynucleotide‐treated cells (P=0.007). This inhibition was reversed by the addition of basic fibroblast growth factor, 20 ng/mL.

Conclusion:

Treatment targeted against basic fibroblast growth factor messenger RNA inhibits growth of HT‐29 human colon cancer cells. This finding may provide a rationale for the therapeutic use of antisense oligodeoxynucleotides targeted at basic fibroblast growth factor for the treatment of colon cancer.
Pharmacokinetics and pharmacodynamics of esomeprazole, the S‐isomer of omeprazole
Authors: Andersson T. , RÖhss K. , Bredberg E. , Hassan‐Alin M.
Published: March 2003

Background:

Esomeprazole, the S‐isomer of omeprazole, is the first proton pump inhibitor developed as a single isomer for the treatment of acid‐related diseases.

Aim:

To examine the pharmacokinetics and pharmacodynamics of esomeprazole.

Methods:

In a crossover study, 12 healthy males received 5, 10 or 20 mg of esomeprazole, or 20 mg of omeprazole, once daily over 5 days. The pharmacokinetics and effects on pentagastrin‐stimulated peak acid output of esomeprazole and omeprazole were studied on days 1 and 5.

Results:

The area under the curve (AUC) of both esomeprazole and omeprazole increased from day 1 to day 5. The correlation between acid inhibition and AUC for esomeprazole could be well described with a sigmoid Emax model. The mean inhibition values of the pentagastrin‐stimulated peak acid output on day 1 for 5, 10 and 20 mg of esomeprazole were 15%, 29% and 46%, respectively; the corresponding day 5 values were 28%, 62% and 90%. The mean inhibition values of the pentagastrin‐stimulated peak acid output for omeprazole were 35% (day 1) to 79% (day 5).

Conclusions:

The pharmacokinetics of esomeprazole are time and dose dependent. There was a good correlation between AUC and effect for esomeprazole. These data suggest an increased acid inhibitory effect of esomeprazole compared to omeprazole.
The treatment of inflammatory bowel disease with 6‐mercaptopurine or azathioprine
Authors: Nielsen O. H. , Vainer B. , Rask‐Madsen J.
Published: March 2003

The thioguanine derivative, azathioprine, is a prodrug of 6‐mercaptopurine that is further metabolized by various enzymes present in the liver and gut. Azathioprine and 6‐mercaptopurine have been used in the treatment of inflammatory bowel disease, i.e. ulcerative colitis and Crohn’s disease, for more than 30 years. However, widespread use of azathioprine or 6‐mercaptopurine in inflammatory bowel disease is of more recent origin, the primary reason being a long‐standing debate on the efficacy of these agents in inflammatory bowel disease. Both drugs are slow acting, which is why clinical efficacy cannot be expected until several weeks or even months of treatment have elapsed. Consequently, azathioprine and 6‐mercaptopurine have no place as monotherapy in the treatment of acute relapsing inflammatory bowel disease.

Today, azathioprine and 6‐mercaptopurine are the most commonly used immunomodulatory drugs in the treatment of inflammatory bowel disease. Their clinical effects are probably identical, although their exact mode of action is still unknown. The mode of action of azathioprine is thought to be multifactorial, including conversion to 6‐mercaptopurine (which acts as a purine antimetabolite), possible blockade of thiol groups by alkylation, inhibition of several pathways in nucleic acid biosynthesis (preventing proliferation of cells involved in the determination and amplification of the immune response) and damage to DNA through the incorporation of thiopurine analogues. However, 6‐thioguanine nucleotides may accumulate in toxic doses in myeloid precursor cells, resulting in life‐threatening myelosuppression. Azathioprine and 6‐mercaptopurine are further known to alter lymphocyte function, reduce the number of lamina propria plasma cells and affect natural killer cell function.

The purpose of this comprehensive review is to suggest guidelines for the application of azathioprine and 6‐mercaptopurine in the treatment of inflammatory bowel disease.
Effect of inhibition of gastric acid secretion on antropyloroduodenal motor activity and duodenal acid hypersensitivity in functional dyspepsia
Authors: Schwartz M. P. , Samsom M. , Van Berge Henegouwen G. P. , Smout A. J. P. M.
Published: March 2003

Background:

Heightened visceroperception and a decreased duodenal motor response to intraduodenal acid infusion have been reported in functional dyspepsia.

Aim:

To investigate the effect of treatment with a proton pump inhibitor on sensorimotor impairment in 19 patients with functional dyspepsia.

Methods:

Patients were assigned double‐blind to pantoprazole (n=10) or placebo (n=9) treatment for 2 weeks. Antropyloroduodenal manometry was performed before and after treatment, using a 21‐channel catheter, and the responses to intraduodenal infusion of 5 mL of saline and acid were assessed. Nausea, fullness and epigastric pain were scored before and after each infusion.

Results:

Acid induced a modest duodenal motor response and suppression of antral pressure waves, not altered by either treatment. However, acid evoked isolated pyloric pressure waves after pantoprazole treatment (P < 0.02), and not after placebo. Saline induced no motor response. Acid (not saline) induced nausea, both before and after treatment in both groups (all P < 0.05). Subgroup analysis of the seven acid‐hypersensitive patients (37%) showed a tendency towards a decrease in nausea in all four pantoprazole‐treated patients (P=0.07), in contrast to the three placebo‐treated patients (P=1.0).

Conclusions:

In functional dyspepsia, pantoprazole influenced the acid‐induced duodenogastric feedback mechanism, but not the impaired duodenal motor response. Duodenal acid hypersensitivity was decreased to some extent.
Efficacy of low‐dose clarithromycin triple therapy and tinidazole‐containing triple therapy for Helicobacter pylori eradication
Authors: Choi I. J. , Jung H. C. , Choi K. W. , Kim J. H. , Ahn D. S. , Yang U. S. , Rew J. S. , Lee S. I. , Rhee J. C. , Chung I. S. , Chung J. M. , Hong W.‐S.
Published: March 2003

Background:

Proton pump inhibitor‐based triple therapies are recommended as the first‐line treatment for Helicobacter pylori eradication.

Aim:

To evaluate the efficacies of low‐dose clarithromycin triple therapy and tinidazole‐containing triple therapy in a metronidazole resistance prevalent area and to compare the efficacies with standard triple therapy.

Methods:

In a randomized, multicentre, prospective study, a total of 352 patients with duodenal ulcer or non‐ulcer dyspepsia were randomly divided into three groups according to the administered regimen: OAC250 group (omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 250 mg), OAC500 group (omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg) and OTC group (omeprazole, 20 mg, tinidazole, 500 mg, and clarithromycin, 500 mg). The three groups received each regimen twice daily for 7 days. Upper gastrointestinal endoscopy was performed before and 4 weeks after treatment. H. pylori status was determined by rapid urease test and 13C urea breath test.

Results:

The eradication rates in the OAC250, OAC500 and OTC groups were 76.2%, 65.7% and 64.8% (95% confidence interval: 67.9–84.4%, 56.7–74.8% and 55.7–73.9%), respectively, by intention‐to‐treat analysis (P=0.149) and 92.8%, 87.2% and 84.1% (95% confidence interval: 84.4–97.3%, 77.9–93.8% and 73.9–91.2%), respectively, by per protocol analysis (P=0.088). All regimens were well tolerated and compliance was excellent.

Conclusions:

Both low‐dose clarithromycin triple therapy and tinidazole‐containing triple therapy are effective and safe regimens for H. pylori eradication.
The epidemiology and natural history of Crohn’s disease in population‐based patient cohorts from North America: a systematic review
Authors: Loftus E. V. , Schoenfeld P. , Sandborn W. J.
Published: March 2003

Aim:

To quantify, through systematic review, the epidemiology and natural history of Crohn’s disease in North America.

Methods:

The selected articles contained: (i) population‐based samples of patients followed from the time of diagnosis; and (ii) objective diagnostic criteria for disease. Studies on the natural history of Crohn’s disease also contained sufficient follow‐up.

Data collection and analysis:

For prevalence studies, data on the incidence, prevalence, gender and age at diagnosis were extracted. For natural history studies, data on the disease activity, use of medications and surgery were extracted.

Main results:

The prevalence of Crohn’s disease in North America ranges from 26.0 to 198.5 cases per 100 000 persons. The incidence rates range from 3.1 to 14.6 cases per 100 000 person‐years. Most patients have a chronic intermittent disease course, while 13% have an unremitting disease course and 10% have a prolonged remission. Less than half require corticosteroids at any point. During any given year, approximately 10% are treated with corticosteroids and 30% are treated with 5‐aminosalicylates. Up to 57% of patients require at least one surgical resection.

Conclusions:

Between 400 000 and 600 000 patients in North America have Crohn’s disease, and the natural history is marked by frequent exacerbations requiring treatment with corticosteroids, 5‐aminosalicylate products and surgery.
Topical mononitrate treatment in patients with anal fissure
Authors: Tankova L. , Yoncheva K. , Muhtarov M. , Kadyan H. , Draganov V.
Published: March 2003

Aim:

To assess the efficacy and patient compliance of topical mononitrate hydrogel for the treatment of anal fissure.

Materials and methods:

Nineteen patients with symptomatic chronic anal fissures were randomly allocated to receive either active (10 patients) or placebo (nine patients) gel treatment. Rectal administration of hydrogel containing 0.2% isosorbide‐5‐mononitrate was prescribed. Patients were instructed on its application to the anal canal twice daily for 3 weeks. A questionnaire was used to determine patient compliance with therapy. Anal manometry was performed before and after therapy.

Results:

At the end of therapy, the fissures were healed in 80% of actively treated patients compared with 22% of the control group. There was a mean reduction of 28% in mean resting anal pressure. Two actively treated patients (20%) suffered from mild headache relieved with oral analgesics and menthol lozenges. Faecal incontinence was not observed. There were no recurrences during at least 3 months of follow‐up.

Conclusions:

Topical mononitrate gel therapy of anal fissures is an effective and safe approach. In this study, the few cases of headache were rapidly relieved with oral analgesia and menthol lozenges.
Antioxidant effects of herbal therapies used by patients with inflammatory bowel disease: an in vitro study
Authors: Langmead L. , Dawson C. , Hawkins C. , Banna N. , Loo S. , Rampton D. S.
Published: March 2003

Background:

Herbal remedies used by patients for treatment of inflammatory bowel disease include slippery elm, fenugreek, devil’s claw, Mexican yam, tormentil and wei tong ning, a traditional Chinese medicine. Reactive oxygen metabolites produced by inflamed colonic mucosa may be pathogenic. Aminosalicylates (5‐ASA) are antioxidant and other such agents could be therapeutic.

Aims:

To assess the antioxidant effects of herbal remedies in cell‐free oxidant‐generating systems and inflamed human colorectal biopsies.

Methods:

Luminol‐enhanced chemiluminescence in a xanthine/xanthine oxidase cell‐free system was used to detect superoxide scavenging by herbs and 5‐ASA, and fluorimetry to define peroxyl radical scavenging using a phycoerythrin degradation assay. Chemiluminescence was used to detect herbal effects on generation of oxygen radicals by mucosal biopsies from patients with active ulcerative colitis.

Results:

Like 5‐ASA, all herbs, except fenugreek, scavenged superoxide dose‐dependently. All materials tested scavenged peroxyl dose‐dependently. Oxygen radical release from biopsies was reduced after incubation in all herbs except Mexican yam, and by 5‐ASA.

Conclusions:

All six herbal remedies have antioxidant effects. Fenugreek is not a superoxide scavenger, while Mexican yam did not inhibit radical generation by inflamed biopsies. Slippery elm, fenugreek, devil’s claw, tormentil and wei tong ning merit formal evaluation as novel therapies in inflammatory bowel disease.
Integrated acidity and rabeprazole pharmacology
Authors: Gardner J. D. , Perdomo C. , Sloan S. , Hahne W. F. , Barth J. A. , Rodriguez‐Stanley S. , Robinson M.
Published: March 2003

Background:

Integrated gastric and oesophageal acidity can be calculated from measurements of gastric and oesophageal pH and used to quantify gastric and oesophageal acidity over time. Rabeprazole is a new proton pump inhibitor that is effective in treating gastro‐oesophageal reflux disease (GERD).

Aim:

To use measurement of integrated gastric and oesophageal acidity to determine the onset, duration and overall effect of rabeprazole in subjects with GERD.

Methods:

Subjects with GERD were required to have oesophageal pH ≤ 4 for at least 10% of a 24‐h recording. Effects of 20 mg rabeprazole on 24‐h gastric and oesophageal pH were measured on days 1 and 7 of dosing. Integrated gastric and oesophageal acidity were calculated from time‐weighted average hydrogen ion concentrations at each second of the 24‐h record.

Results:

At steady‐state, 20 mg rabeprazole inhibited gastric acidity by 89% and oesophageal acidity by 95%. The first dose of rabeprazole inhibited gastric and oesophageal acidity by at least 70% of the steady‐state effect. Oesophageal acidity could be divided into monophasic and biphasic patterns, and rabeprazole had different effects on oesophageal and gastric acidity in these two GERD subpopulations. The onset of action of the first dose of rabeprazole on gastric acidity was 4 h and on oesophageal acidity was 4 h in monophasic subjects and 7 h in biphasic subjects. Integrated acidity was more sensitive than time pH ≤ 4 in measuring the inhibitory actions of rabeprazole.

Conclusions:

Integrated gastric and oesophageal acidity are quantitative measurements that provide useful and novel information regarding the pathophysiology of GERD as well as the impact of antisecretory agents such as rabeprazole.
Interferon‐α plus ribavirin for 12 months increases the sustained response rates in chronic hepatitis C relapsers
Authors: Moreno‐Monteagudo J. A. , Castro A. , De Pedro A. , Lorenzo J. A. , Fernández‐Bermejo M. , Lopez S. , García‐Buey L. , Borque M. J. , Pedreira J. D. , Moreno‐Otero R.
Published: March 2003

Background:

The effectiveness and tolerability of combination therapy for 12 months have not been evaluated sufficiently in chronic hepatitis C relapsers to interferon.

Aims:

To evaluate the sustained response to interferon plus ribavirin for 12 months in chronic hepatitis C relapsers.

Methods:

We included 55 chronic hepatitis C relapsers in a 12‐month treatment protocol with interferon (3 MU thrice weekly) plus ribavirin (1–1.2 g/day). The effectiveness was evaluated using serum aminotransferase and hepatitis C virus RNA levels, alanine aminotransferase normalization and viraemia clearance after 12 months, defining the end‐of‐treatment response, and 6 months after completion of therapy, defining the sustained response. Adverse effects were recorded.

Results:

End‐of‐treatment response and sustained response were achieved in 47 (85%) and 37 (67%) patients, respectively; there were 10 (21%) relapsers after combination therapy. Predictive factors of sustained response included the genotype (non‐1 95% vs. 1 48%; P < 0.001), lower viraemia (503 917 ± 553 230 vs. 901 393 ± 548 267 copies/mL; P < 0.005), higher alanine aminotransferase levels (137 ± 75 vs. 103 ± 41 IU/L; P < 0.05) and a lower γ‐glutamyl transpeptidase/alanine aminotransferase ratio (0.30 ± 0.23 vs. 0.49 ± 0.39; P < 0.05). Tolerance to therapy was good, with no withdrawals.

Conclusions:

Interferon plus ribavirin treatment for 12 months in chronic hepatitis C relapsers yields high sustained response rates and is well tolerated. The sustained response is related to a non‐1 genotype, lower baseline viraemia, higher alanine aminotransferase level and a lower γ‐glutamyl transpeptidase/alanine aminotransferase ratio.
Immunosuppressants in distal ulcerative colitis
Authors: Falasco G. , Zinicola R. , Forbes A.
Published: March 2003

Background:

Distal ulcerative colitis may prove to be resistant to steroids and aminosalicylates, but total colectomy is more difficult to justify than in severe extensive colitis. Immunosuppression is of established benefit in generalized colitis, but there are no data available specific to distal disease.

Aim:

To determine whether the protocol‐driven use of immunosuppressants in resistant distal ulcerative colitis is of similar efficacy and safety to that in extensive disease.

Methods:

Two hundred and twenty‐eight patients with distal ulcerative colitis seen in a 5‐year period were identified from a prospective database. Details of 52 who had received immunosuppression were analysed.

Results:

The 52 patients received 68 courses of therapy (53 azathioprine, five mercaptopurine, 10 ciclosporin). The thiopurines yielded clinically valuable responses in only 43% of courses, with failure of response in 16% and toxicity in 34%. Ciclosporin was helpful on only two of 10 occasions. Eight patients required total colectomy. Adverse events were typical of those normally associated with immunosuppressants, with potential risk to life in seven patients; treatment was discontinued because of toxicity on a total of 31% of occasions.

Conclusions:

Immunosuppression appears to be of lower efficacy and higher toxicity in resistant distal colitis than when used in more extensive colitis.
Primary resistance to antibiotics and its clinical impact on the efficacy of Helicobacter pylori lansoprazole‐based triple therapies
Authors: Poon S. K. , Chang C. S. , Su J. , Lai C. H. , Yang C. C. , Chen G. H. , Wang W. C.
Published: March 2003

Aim:

To evaluate Helicobacter pylori primary resistance and its clinical impact on the efficacy of two lansoprazole‐based eradication triple therapies.

Methods:

H. pylori‐positive patients (n=228) were randomized to receive one of the 1‐week regimens: lansoprazole 30 mg, clarithromycin 500 mg and amoxicillin 1 g (LAC), or lansoprazole 30 mg, clarithromycin 500 mg and metronidazole 500 mg (LMC), each given twice daily. H. pylori status was assessed by 13C‐urea breath test and culture at diagnosis and by 13C‐urea breath test 6 weeks after therapy. Antibiotic susceptibility was determined by E‐test (n=98).

Results:

The eradication rates with per protocol/ intention‐to‐treat analyses were: LAC (n=95/114) 83%/69% and LMC (n=96/114) 85%/72%. Primary resistance was 11% for clarithromycin, 41% for metronidazole and 0% for amoxicillin. Eradication in metronidazole‐susceptible/‐resistant strains was 85%/82% in LAC and 83%/63% in LMC. Significantly lower cure rates were observed in clarithromycin‐resistant patients treated with LAC (95% vs. 0%, P < 0.001) and LMC (86% vs. 0%, P < 0.001).

Conclusions:

One‐week LAC and LMC are similarly effective therapies. Clarithromycin resistance significantly affected H. pylori eradication in both regimens.
Effect of Helicobacter pylori eradication on oesophageal acid exposure in patients with reflux oesophagitis
Authors: Wu J. C. Y. , Chan F. K. L. , Wong S. K. H. , Lee Y. T. , Leung W. K. , Sung J. J. Y.
Published: March 2003

Background:

The effect of Helicobacter pylori eradication on reflux oesophagitis is unclear.

Aim:

To study the effect of H. pylori eradication on oesophageal acid exposure and disease severity in patients with reflux oesophagitis.

Methods:

Patients with reflux oesophagitis and H. pylori infection were recruited for 24‐h oesophageal pH‐metry. They were then randomly assigned to receive either treatment for H. pylori eradication (1‐week omeprazole‐based triple therapy, followed by 7‐week omeprazole) or omeprazole alone (8‐week omeprazole). Uninfected patients were recruited as controls. Endoscopy, pH monitoring and symptom assessment were repeated at 26 weeks.

Results:

Forty patients (25 H. pylori‐positive and 15 uninfected) with erosive oesophagitis were studied. Fourteen were randomized to receive treatment for H. pylori eradication and 11 to receive omeprazole alone. There was no difference in the percentage of time the oesophageal pH < 4 before and 26 weeks after treatment among the three groups. However, the percentage of time the oesophageal pH < 2 (P=0.01) and pH < 3 (P=0.02) was significantly increased in patients receiving treatment for H. pylori eradication. Three (21%) patients in the group receiving treatment for H. pylori eradication had worsening of reflux oesophagitis.

Conclusions:

H. pylori eradication increases oesophageal acid exposure and may adversely affect the clinical course of reflux disease in a subset of patients.
Interactions between Helicobacter pylori and other risk factors for peptic ulcer bleeding
Authors: Stack W. A. , Atherton J. C. , Hawkey G. M. , Logan R. F. A. , Hawkey C. J.
Published: March 2003

Aim:

To investigate the role of Helicobacter pylori, expressing the virulence marker CAGA (cytotoxin associated gene product A) in ulcer complications and its interaction with nonsteroidal anti‐inflammatory drugs (NSAIDs) and other risk factors.

Design:

Case control study using conditional logistic regression analysis.

Setting:

University and City Hospitals, Nottingham.

Subjects:

203 consecutive patients with ulcer bleeding and 203 age‐ and sex‐matched controls.

Results:

Ulcer bleeding was more likely with positive H. pylori serology (odds ratio = 3.3, 95% CI: 1.7–6.6 for CagA positive, but only OR = 1.6, 95% CI: 0.7–3.7 for CagA negative serology), current smoking (OR 2.2, 95% CI: 1.04–4.7), aspirin ≤ 300 mg daily (OR 7.7, 95% CI: 2.8–20.6), all other nonsteroidal anti‐inflammatory drugs (NSAIDs: OR 10.6, 95% CI: 3.1–35.7 for ≤ 1 defined daily dose lower and OR 22.6, 95% CI: 6.2–82.0 for higher doses) and past ulcer history (OR 5.6, 95% CI: 2.3–14.1). Aspirin ≤ 300 mg daily was used by 25.1% of patients vs. 7.4% of controls. Smoking only enhanced risk in the presence of H. pylori, with a synergistic interaction (interaction odds ratio = 4.9, 2.4–9.9, P=0.002). Conversely, risks with non‐aspirin NSAIDs were reduced in the presence of H. pylori, particularly if CagA‐positive (interaction odds ratio=0.21, 0.05–0.9, P=0.03).

Conclusions:

CagA positive H. pylori infection is associated with an increased risk of ulcer bleeding. The risk from non‐aspirin NSAIDs is even higher, but is less in H. pylori infected people. Low‐dose aspirin is now commonly associated with ulcer bleeding.
The concept of entero‐colonic encephalopathy, autism and opioid receptor ligands
Authors: Wakefield A. J. , Puleston J. M. , Montgomery S. M. , Anthony A. , O'Leary J. J. , Murch S. H.
Published: March 2003

There is growing awareness that primary gastrointestinal pathology may play an important role in the inception and clinical expression of some childhood developmental disorders, including autism. In addition to frequent gastrointestinal symptoms, children with autism often manifest complex biochemical and immunological abnormalities. The gut–brain axis is central to certain encephalopathies of extra‐cranial origin, hepatic encephalopathy being the best characterized.

Commonalities in the clinical characteristics of hepatic encephalopathy and a form of autism associated with developmental regression in an apparently previously normal child, accompanied by immune‐mediated gastrointestinal pathology, have led to the proposal that there may be analogous mechanisms of toxic encephalopathy in patients with liver failure and some children with autism. Aberrations in opioid biochemistry are common to these two conditions, and there is evidence that opioid peptides may mediate certain aspects of the respective syndromes. The generation of plausible and testable hypotheses in this area may help to identify new treatment options in encephalopathies of extra‐cranial origin.

Therapeutic targets for this autistic phenotype may include: modification of diet and entero‐colonic microbial milieu in order to reduce toxin substrates, improve nutritional status and modify mucosal immunity; anti‐inflammatory/immunomodulatory therapy; and specific treatment of dysmotility, focusing, for example, on the pharmacology of local opioid activity in the gut.
Inhibition of Helicobacter pylori‐induced cyclo‐oxygenase‐2 aggravates NSAID‐caused gastric damage in Mongolian gerbils
Authors: Futagami S. , Hiratsuka T. , Wada K. , Tatsuguchi A. , Tsukui T. , Miyake K. , Akamatsu T. , Hosone M. , Sakamoto C. , Kobayashi M.
Published: March 2003

Background:

The effect of Helicobacter pylori infection on non‐steroidal anti‐inflammatory drug‐induced gastric mucosal injury is controversial.

Aim:

To examine the effect of the interaction between H. pylori and non‐steroidal anti‐inflammatory drugs on gastric mucosal injury.

Methods:

Mongolian gerbils infected with H. pylori were treated with indometacin at 8 mg/kg for 2 days or 7 days. Mucosal damage was assessed by macroscopic and histological examination, and myeloperoxidase activity was measured as an index of neutrophil infiltration. The expression levels of cyclo‐oxygenase proteins were determined by Western blot analysis and cyclo‐oxygenase activity.

Results:

A 2‐day course of indometacin did not cause an increase in gastric damage in H. pylori‐infected Mongolian gerbils compared to uninfected gerbils, while a 7‐day course of indometacin caused additive gastric damage in H. pylori‐infected animals. H. pylori infection induced cyclo‐oxygenase‐2 expression in the stomach. Treatment with indometacin for 2 days did not significantly affect cyclo‐oxygenase activity in H. pylori‐infected animals, while treatment for 7 days inhibited both cyclo‐oxygenase‐1 and cyclo‐oxygenase‐2 activities. Pre‐treatment with a selective cyclo‐oxygenase‐2 inhibitor aggravated mucosal injury in H. pylori‐infected animals treated or not treated with indometacin for 2 days.

Conclusions:

Our results suggest that cyclo‐oxygenase‐2 protein induced by H. pylori infection may be involved in the defence of the gastric mucosa against damage caused by non‐steroidal anti‐inflammatory drugs. Therefore, inhibition of cyclo‐oxygenase‐2 activity may enhance non‐steroidal anti‐inflammatory drug‐caused gastric damage in H. pylori‐infected animals.
Monitoring for drug side‐effects in inflammatory bowel disease
Authors: Cunliffe R. N. , Scott B. B.
Published: March 2003

The side‐effects suitable for monitoring in patients with inflammatory bowel disease being treated with the four main groups of drugs (5‐aminosalicylic acid preparations, azathioprine and 6‐mercaptopurine, methotrexate, and corticosteroids) are reviewed. On the basis of the reported frequency, severity and timing of side‐effects, a practical scheme of monitoring is recommended. This includes a baseline measurement of full blood count, creatinine and liver function tests in all patients. In the absence of worrying symptoms, we recommend the following: (i) no monitoring for sulfasalazine; (ii) for other 5‐aminosalicylic acid preparations, the meas‐ urement of creatinine at 6 and 12 months and then annually; (iii) for azathioprine/6‐mercaptopurine, thiopurine methyltransferase genotype/phenotype determination has no role in treatment monitoring, but a full blood count at 2 weeks, 1 month, 3 months and then every 3 months should be performed; (iv) for methotrexate, a full blood count and liver function tests should be performed every 3 months; (v) for steroids, dual energy X‐ray absorptiometry bone scanning should be performed at the start of therapy, every year in which steroids are used if the T score is < 0, and every 3–5 years if the T score is > 0.
Comparison of the main oesophageal pathophysiological characteristics between short‐ and long‐segment Barrett's oesophagus
Authors: Zentilin P. , Conio M. , Mele M. R. , Mansi C. , Pandolfo N. , Dulbecco P. , Gambaro C. , Tessieri L. , Iiritano E. , Bilardi C. , Biagini R. , Vigneri S. , Savarino V.
Published: March 2003

Aim:

To assess the oesophageal manometric characteristics and 24‐h pH profiles of patients with both short‐segment and long‐segment Barrett's oesophagus and compare them with those of patients with reflux oesophagitis and controls.

Methods:

Seventy‐nine patients who had undergone upper digestive endoscopy were recruited: 16 had short‐segment Barrett's oesophagus, 13 had long‐segment Barrett's oesophagus, 25 had grade III oesophagitis according to the Savary–Miller classification and 25 were used as controls. The diagnosis of Barrett's oesophagus was based on the histological detection of specialized intestinal metaplasia, which extended < 3 cm into the oesophagus in patients with short‐segment disease and > 3 cm in patients with long‐segment disease. All subjects underwent oesophageal manometry and basal 24‐h oesophageal pH monitoring.

Results:

The lower oesophageal sphincter pressure was significantly lower in patients with reflux oesophagitis and short‐segment and long‐segment Barrett's oesophagus than in controls (P=0.0004–0.0001), but there was no difference among the three reflux groups. The peristaltic wave amplitude of patients with long‐segment Barrett's oesophagus was significantly lower than that of controls (P=0.002) and patients with short‐segment Barrett's oesophagus (P=0.02), but was no different from that of patients with reflux oesophagitis. The percentage of non‐propagated wet swallows was significantly higher in patients with reflux oesophagitis and short‐segment and long‐segment Barrett's oesophagus when compared with that of controls (P=0.0004–0.0001). The total percentage of time the oesophagus was exposed to pH < 4.0 was significantly higher in patients with reflux oesophagitis and short‐segment and long‐segment Barrett's oesophagus (P=0.0001) than in controls, and was higher in patients with long‐segment disease than in those with short‐segment disease (P=0.01).

Conclusions:

Long‐segment Barrett's oesophagus is characterized by a greater impairment of peristaltic wave amplitude and a higher oesophageal acid exposure than is short‐segment Barrett's oesophagus. However, both forms are linked to increased acid reflux.
Prospective audit of gastroscopy under the `three‐day rule': a regional initiative in Italy to reduce waiting time for suspected malignancy
Authors: Parente F. , Bargiggia S. , Bianchi Porro G.
Published: March 2003

Background:

A regional initiative, called the `three‐day rule', has recently been introduced in Italy to facilitate the earlier diagnosis of malignancy. It requires patients with suspected severe diseases to have a diagnostic procedure performed within three working days of referral by a general practitioner.

Aim:

To assess prospectively the effectiveness and compliance with the three‐day rule for upper digestive malignancies.

Methods:

We compared patients referred for gastroscopy under the three‐day rule initiative with contemporaneous open access referrals over a 12‐month period at a single large teaching hospital in west Milan. We compared the prevalence of malignancies and other serious non‐neoplastic diseases as well as the waiting times in the two groups. The appropriateness of the indications for each referral was also reviewed by a gastroenterologist blind to the outcome of the test.

Results:

One hundred and forty‐two patients referred for gastroscopy under the three‐day rule scheme and 767 routine referrals were studied. Significantly more oesophageal/gastric cancers (6% vs. 1%) and serious benign gastrointestinal lesions (grade II–III oesophagitis or peptic ulcer) were diagnosed in three‐day rule patients in comparison with routine referrals (P < 0.05). The rate of inappropriate referral was significantly lower in the three‐day rule group than in the open access group (39% vs. 22%) (P < 0.01). The estimated cost of the three‐day rule scheme (in extra list examinations alone) was 10 780 euros, with about 1198 euros per diagnosis of cancer, but only 229.5 euros per `useful' diagnosis (including peptic ulcer disease and oesophagitis).

Conclusions:

Significantly more upper gastrointestinal cancers and serious benign diseases can be found within a short period to comply with the three‐day rule scheme. However, some general practitioners appear to over‐interpret alarm symptoms, leading to some inappropriate referrals. Better awareness of appropriate urgent referral criteria is needed in order to ensure that the best use is made of the resources available.