bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of current and former cigarette smoking on the clinical course of Crohn’s disease
Authors: Cosnes  , Carbonnel  , Carrat  , Beaugerie  , Cattan  , Gendre
Published: March 2003

Background

: Cigarette smoking is associated with a more severe course of Crohn’s disease, but individual factors determining this effect are poorly known and it is not clear whether smoking cessation is associated with an improvement in the disease activity.

Aim

: To assess the factors determining the harmful effect of smoking in individuals with Crohn’s disease.

Methods

: A total of 622 consecutive patients with Crohn’s disease and Crohn’s disease activity index <200 were enrolled in a prospective 12–18 month cohort study. Patients were classified as current smokers, former smokers, or non‐smokers. Alcohol consumption, oral contraceptive use, body mass index, and blood lipid levels were also recorded. The main outcome measure was the rate of flare‐up.

Results

: A total of 139 current smokers (46%) developed a flare‐up, vs. 79 non‐smokers (30%) and 13 former smokers (23%). The relative risk of flare‐up adjusted for confounding factors was 1.35 (1.03–1.76) in current smokers. This risk was increased in patients with previously inactive disease and in those who had no colonic lesions. It became significant above a threshold of 15 cigarettes per day. Former smokers behaved like non‐smokers. Obesity, dyslipidaemia, and alcohol consumption had no significant effect.

Conclusions

: Current smoking, particularly heavy smoking, markedly increases the risk of flare‐up in Crohn’s disease. Former smokers have a risk similar to that of non‐smokers.
The effect of an inhibitor of matrix metalloproteinases on colonic inflammation in a trinitrobenzenesulphonic acid rat model of inflammatory bowel disease
Authors: Sykes  , Bhogal  , Brampton  , Chander  , Whelan  , Parsons  , Bird
Published: March 2003

Background

: Recent publications have reported that matrix metalloproteinases (MMPs) are expressed in colonic tissue taken from ulcerative colitis and Crohn’s disease patients.

Aim

: To evaluate the effects of a matrix metalloproteinase inhibitor, marimastat, on colonic inflammation in experimental colitis induced by trinitrobenzenesulphonic acid (TNBS)‐ethanol in the rat.

Methods

: Rats were dosed (by mouth) for 7 days (b.d.) with either sulphasalazine (50 mg/kg), marimastat (40 mg/kg) or vehicle. TNBS‐ethanol was administered rectally on the 4th day of dosing. On the last day of dosing, colons were removed and assessed for inflammation using myeloperoxidase activity, production of soluble TNFα (tumour necrosis factor α), clinical score and histological assessment. In addition, the bioavailability and effect of marimastat on a range of MMPs were assessed in‐vitro.

Results

: In this study we have confirmed that marimastat is a broad spectrum MMPI with a bioavailability of 5%. TNBS rats dosed with sulphasalazine had a significantly lower (P < 0.05) myeloperoxidase activity, TNFα production and a markedly lower clinical score. Similarly, rats dosed with marimastat had a significantly lower (P < 0.05) myeloperoxidase activity and clinical score, but the TNFα production was not significantly reduced.

Conclusions

: Dosing rats with TNBS‐induced colitis using sulphasalazine or marimastat produced a significant reduction in tissue injury and inflammation.
Triple therapy for Helicobacter pylori eradication: a comparison of pantoprazole once versus twice daily
Authors: Bardhan  , Dillon  , Axon  , Cooper  , Tildesley  , Wyatt  , Gatz  , Braun
Published: March 2003

Background:

Proton pump inhibitor‐based triple therapy is recommended as treatment for Helicobacter pylori eradication. The proton pump inhibitor may be given once or twice daily. However, little information is available on how these two treatment strategies compare.

Methods:

H. pylori‐positive patients (two positive test results) with endoscopy‐proven healed duodenal ulcer or non‐ulcer dyspesia were randomly allocated to 1 week of double‐blind treatment with pantoprazole 40 mg once or twice daily, plus clarithromycin 250 mg and metronidazole 400 mg twice daily. Eradication was defined as a negative 13C‐urea breath test (13C‐UBT) and histology, 4–5 weeks post‐treatment. The follow‐up phase comprised 12 months off therapy, with 13C‐UBT at 6 and 12 months.

Results:

Two hundred and four patients received treatment: pantoprazole once daily (×1), n=104; twice daily (×2), n=100. Eradication rates were 84% in both the pantoprazole ×1 and pantoprazole ×2 groups by modified intention‐to‐treat analysis and 89% and 87%, respectively, by per protocol analysis. Metronidazole resistance was found in 44% of pre‐treatment cultures of H. pylori. Eradication rates were similar in susceptible (72%) and resistant (75%) strains. During follow‐up, recrudescence of infection occurred in 3/118 patients.

Conclusion:

When using pantoprazole plus clarithromycin and metronidazole, the proton pump inhibitor can be used once daily without loss of efficacy.
The effects of 1‐year gluten withdrawal on bone mass, bone metabolism and nutritional status in newly‐diagnosed adult coeliac disease patients
Authors: Sategna‐Guidetti  , Grosso  , Grosso  , Mengozzi  , Aimo  , Zaccaria  , Di Stefano  , Isaia
Published: March 2003

Objectives:

To evaluate the impact of a 1‐year gluten‐free diet on bone metabolism and nutritional status in coeliac disease.

Methods:

Bone mineral density, serum indices of bone remodelling, clinical and biochemical nutritional assessment were evaluated in 86 consecutive newly‐diagnosed, biopsy proven, coeliac disease patients (untreated). A complete revaluation, including intestinal biopsy, was repeated within 1 year of dietary treatment (treated).

Results:

Untreated: according to WHO criteria, 34% of patients had a normal bone mineral density, 40% had osteopenia and 26% osteoporosis. Between males and females there were no statistical differences in bone metabolism or in most of the nutritional indices, while, between fertile and postmenopausal women, bone mineral density and several bone metabolism markers were significantly different. Compared to subjects with a normal bone mineral density, osteopenics had higher bone specific alkaline phosphatase (BAP) and Bone‐Gla‐protein (BGP) values. In patients with a concomitant BAP increase and 25OH vitamin D serum level reduction, bone mineral density and several bone turnover markers were statistically different compared to patients without such a serological pattern. Treated: notwithstanding intestinal biopsy which showed a mucosal recovery in only 57%, gluten‐free diet led, even in postmenopausal women, to a significant improvement in bone mineral density, bone metabolism and nutrition, except for folic acid, albumin and pre‐albumin serum levels which persisted as abnormal in patients with obdurate mucosal impairment.

Conclusions:

Coeliac disease patients are at high risk for developing a low bone mineral density and bone turnover impairment. A gluten‐free diet can improve this situation even in postmenopausal women and in patients with incomplete mucosal recovery.
Low‐dose intravenous erythromycin: effects on postprandial and fasting motility of the small bowel
Authors: Medhus  , Bondi  , Gaustad  , Husebye
Published: March 2003

Background

: Erythromycin is a motilin agonist and its effects on gastrointestinal motility are dependent on both dose and whether it is administered during the postprandial or fasting state.

Aim

: To study the motility response of the small bowel to a low dose of intravenous erythromycin after meal intake and during fasting.

Methods

: Eighteen healthy subjects with mean age of 25 years were studied by small bowel manometry. Erythromycin was administered intravenously (0.75 mg per kg body weight) during 20 min in the postprandial (n=9) and the fasting state (n=9), and the motility response was recorded.

Results

: Erythromycin significantly reduced the frequency of propagated contractions (P < 0.001) and the amplitude of contractions (P < 0.02) in the small bowel during established postprandial motility. During the fasting state, erythromycin invariably initiated a phase III‐like activity, which was similar to the spontaneous nocturnal phase III and migrated significantly more slowly than the diurnal phase III (P < 0.01).

Conclusions

: A low dose of erythromycin administered intravenously during the postprandial state significantly inhibits small bowel motility, whereas administration during the fasting state initiates a phase III resembling the nocturnal rather than the diurnal phase III. These effects of erythromycin may indicate interference with vagal pathways. Due to its inhibitory effects, the clinical use of erythromycin in patients with hypomotility should be reconsidered, and the potential usefulness of these effects in patients with exaggerated intestinal motility deserves further attention.
Gastrointestinal spread of oral prolonged‐release mesalazine microgranules (Pentasa) dosed as either tablets or sachet
Authors: Wilding  , Kenyon  , Hooper
Published: March 2003

Background

: There is increasing interest in using higher dosages of mesalazine for the treatment of inflammatory bowel disease; however, with current mesalazine products this involves the use of 8–16 tablets per day.

Aim

: To evaluate the disposition, dispersion and movements of Pentasa prolonged‐release microgranules following single dosing of either tablets (2 × 500 mg) or a new 1 g sachet (unit dose, microgranules in a foil bag).

Methods

: A randomized crossover study in eight healthy volunteers was undertaken. Both formulations were radiolabelled by neutron activation and dosed in the fasted state. Location of the preparations in the bowel was assessed over 24 h by scintigraphy.

Results

: Dissolution testing at pH 7.5 showed comparable in vitro mesalazine release properties for the tablet and sachet preparations. In vivo disposition of the microgranules administered as either tablets or sachet was comparable in terms of gastric emptying, small intestinal transit and colon arrival.

Conclusions

: Pentasa sachets 1 g unit dose offers the same release of mesalazine as Pentasa 500 mg tablets. Drug release occurs throughout the gastrointestinal tract from stomach to colon, with the advantage of fewer oral doses and ease of swallowing.
Clinical and fiscal impact of lansoprazole intolerance in veterans with gastro‐oesophageal reflux disease
Authors: Gerson  , Hatton  , Ryono  , Jones  , Pulliam  , Sampliner  , Triadafilopoulos  , Fass
Published: March 2003

Background:

Omeprazole was replaced by lansoprazole as the only proton pump inhibitor on the Veterans Affairs (VA) formulary in February 1997. We aimed to assess the clinical and fiscal impact of this conversion at two VA hospitals.

Methods:

We identified lansoprazole intolerant patients using pharmacy databases. We reviewed medical records to obtain data regarding reasons for lansoprazole intolerance. The costs of the formulary change and the savings to the VA were calculated.

Results:

A total of 3833 patients required long‐term proton pump inhibitor therapy; 2224 (58%) were started on lansoprazole and 1479 (39%) were converted from omeprazole to lansoprazole. The remaining 130 (3.4%) patients were never converted from omeprazole to lansoprazole. Of the 3833 patients, 325 (8.5%) currently receive omeprazole therapy; of these, 195 out of 3703 (5.3%) patients are true lansoprazole failures; 172 of these 195 patients completed the study. Most (87%) of the lansoprazole intolerant patients received prior omeprazole. Discontinuation of lansoprazole was due to poor symptom control in 69% and/or side‐effects (22%) including diarrhoea (10%), abdominal pain (5%), or hives (1%). The 1‐year cost of managing lansoprazole failure in 195 patients was $61 690. However, the savings to the VA during the same time period, which totalled $321 360, more than offset the costs associated with the conversion.

Conclusions:

Lansoprazole intolerance requiring omeprazole conversion occurred in 5% of veterans on proton pump inhibitor therapy for chronic gastro‐oesophageal reflux disease (GERD) symptoms and in 10% of patients with prior omeprazole success. The VA realized substantial cost savings in association with the formulary change.
Diagnostic accuracy of a new non‐invasive enzyme immunoassay for detecting Helicobacter pylori in stools after eradication therapy
Authors: Ishihara  , Kaji  , Kawamura  , Rumi  , Sato  , Okuyama  , Adachi  , Fukuda  , Watanabe  , Hashimoto  , Hirakawa  , Matsushima  , Chiba  , Kinoshita
Published: March 2003

Background:

Helicobacter pylori eradication therapy has been commonly performed for patients with peptic ulcer. An inexpensive, reliable, non‐invasive test would be useful for evaluation of the effectiveness of eradication therapy.

Aim:

To evaluate the diagnostic potential of a new non‐invasive enzyme immunoassay (HpSA) for H. pylori antigen in stools.

Methods:

A total of 112 peptic ulcer patients with H. pylori infection (82 male, 30 female; age range 22–81 years, mean 54 years) received a course of eradication therapy. Four weeks after the end of the therapy, stool samples were collected from all patients and tested using the HpSA. The diagnostic accuracy of the HpSA EIA was evaluated in comparison with the results of a 13C‐urea breath test.

Results:

The diagnostic sensitivity of HpSA EIA after eradication therapy was 90%, the specificity 98%, the positive predictive value 82% and the negative predictive value 99%.

Conclusion:

The HpSA stool test is potentially useful for the diagnosis of H. pylori infection 4 weeks after the end of eradication therapy.
Rifaximin versus chlortetracycline in the short‐term treatment of small intestinal bacterial overgrowth
Authors: Di Stefano  , Malservisi  , Veneto  , Ferrieri  , Corazza
Published: March 2003

Background:

Bacterial overgrowth of the small intestine is a condition characterized by nutrient malabsorption due to an excessive number of bacteria in the lumen of the small intestine. Current treatment is based on empirical courses of broad spectrum antibiotics; few controlled data, with respect to the duration and choice of antibiotic drug, exist at present. The recent availability of rifaximin, a non‐absorbable rifamycin derivative, highly effective against anaerobic bacteria, prompted us to carry out a randomized, double‐blind controlled trial in order to compare its efficacy and tolerability to those of tetracycline, currently considered the first‐choice drug.

Methods:

In 21 patients affected by small intestinal bacterial overgrowth, fasting, peak and total H2 excretion after ingestion of 50 g glucose and severity of symptoms were evaluated before and after a 7‐day course of rifaximin, 1200 mg/day (400  mg t.d.s.), or chlortetracycline, 1 g/day (333 mg␣t.d.s.).

Results:

Fasting, peak and total H2 excretion decreased significantly in the group of patients treated with rifaximin whereas chlortetracycline did not modify these parameters. The H2 breath test normalized in 70% of patients after rifaximin and in 27% of patients after chlortetracycline. The improvement in symptoms was significantly higher in patients treated with rifaximin.

Conclusions:

Rifaximin is a promising, easily‐handled and safe drug for the short‐term treatment of small intestinal bacterial overgrowth.
Pharmacokinetics of Lactobacillus plantarum NCIMB 8826, Lactobacillus fermentum KLD, and Lactococcus lactis MG 1363 in the human gastrointestinal tract
Authors: Vesa  , Pochart  , Marteau
Published: March 2003

Objectives:

Genetically modified lactic acid bacteria may be a way to deliver vaccinal epitopes in the gastrointestinal tract.

Aim:

Three strains of lactic acid bacteria were studied for their pharmacokinetics in the human gastrointestinal tract.

Methods:

The survival of the strains was studied up to the ileum in six subjects each, after ingestion of 150 g of fermented milk. The strains and their concentrations in the products were Lactobacillus fermentum KLD (107 cfu/g), Lactobacillus plantarum NCIMB 8826 (108 cfu/g), and Lactococcus lactis MG 1363 (108 cfu/g). Ileal fluid was aspirated by intestinal intubation and immediately cultured. L. plantarum NCIMB 8826, which was found in high concentrations in the ileum, was studied for its survival in the faeces after consumption of 150 g of fermented milk three times daily for 7 days. Faecal samples were collected for culture.

Results:

The concentration of L. plantarum NCIMB 8826 in the ileum reached 108 cfu/mL after a single dose, with a survival of 7%. L. fermentum KLD and Lc. lactis MG 1363 had lower (0.5 and 1.0%, respectively) and shorter (4 h) survival in the ileum. During the 7‐day ingestion period, L. plantarum NCIMB 8826 reached high concentrations (108 cfu/g) in the faeces, with a survival of 25 ± 29%. None of the strains colonized.

Conclusions:

L. plantarum NCIMB 8826 has a promising pharmacokinetic profile as a candidate vaccine vehicle.
Nitric oxide formation in the dog sphincter of Oddi from nitric oxide donors as measured with in vivo micro‐dialysis
Authors: Yamamoto I. , Fujimura M. , Kihara N. , Kumano K. , Yamada T. , Yamamoto H. , Fujimiya M.
Published: March 2003

Background:

Nitric oxide (NO) is known to play an important role in neurally mediated relaxation of the sphincter of Oddi.

Aim:

We investigated whether NO donors, such as nitroglycerin or zwitterionic polyamine/NO, applied into the common bile duct or intravenously, may induce the relaxation of the sphincter of Oddi by producing NO in the anaesthetized dog.

Methods:

NO production in the sphincter of Oddi was measured by detecting NO oxidation products (NO2– and NO3–) using micro‐dialysis methods.

Results:

Zwitterionic polyamine/NO and nitroglycerin applied into the common bile duct induced a marked increase in NO2– but not NO3–, in the sphincter of Oddi. Intravenous infusion of zwitterionic polyamine/NO and nitroglycerin induced little or no increase in NO2– formation. Nitroglycerin infused into either the common bile duct or intravenously administered produced relaxation of the sphincter of Oddi, but zwitterionic polyamine/NO had no effect on the sphincter of Oddi in spite of the increase in NO2– levels.

Conclusions:

Locally or systemically applied NO donors induce relaxation of the sphincter of Oddi by producing NO, although their mode of action differs in different analogues.
Gastric damage in the rat with nitrogen‐containing bisphosphonates depends on pH
Authors: Blank  , Gibson  , Myers  , Dierckman  , Phipps  , Smith
Published: March 2003

Background:

The use of nitrogen‐containing bisphosphonates (N‐BPs) has been reported to be associated with gastrointestinal intolerance. The fasted, indomethacin‐treated rat provides a model for assessing the gastrointestinal effects of these compounds.

Aims:

The aims of this study were to elucidate the effect of pH on N‐BP‐induced gastric damage, and to evaluate the structure–activity relationship between N‐BP anti‐resorptive and gastric effects.

Methods:

Fasted rats were dosed concomitantly with indomethacin (40 mg/kg, subcutaneously) and an N‐BP (pamidronate, alendronate, or risedronate at 150 or 300 mg/kg, orally), with the N‐BP dosing solutions adjusted to pH 2, 4 or 7. The aminopentane and aminohexane N‐BPs (150, 225 or 300 mg/kg, orally) were only tested at pH 4 only.

Results:

Nitrogen‐containing bisphosphonate‐induced gastric damage was pH‐dependent, with increased damage at increasing pH.

Conclusions:

Gastric damage potential did not correlate with bone anti‐resorptive effects, and the more potent anti‐resorptive N‐BPs were not necessarily more damaging to the stomach.
Helicobacter pylori vaccines—the current status
Authors: Sutton  , Lee
Published: March 2003

In this review, we take a look at the current status in the development of a vaccine against the human pathogenic bacterium, Helicobacter pylori, a major aetiological factor in peptic ulcer disease and gastric adenocarcinoma. Various animal models are now in use from mice infected with H. pylori, through gnotobiotic pigs and primates to ferrets naturally infected with their own Helicobacter, H. mustelae. A significant problem remains the requirement for a suitable mucosal adjuvant. Detoxification or the use of low doses of adjuvants already available may provide a solution and new immune stimulating compounds have been tested with some success. New approaches include the delivery of Helicobacter antigens by DNA immunization, microparticles or live vectors such as attenuated salmonella and the examination of alternative routes of vaccine administration. The phenomenon of post‐immunization gastritis and improvements in vaccine efficacy are also discussed. A major area of interest is the mechanism by which immunization actually influences Helicobacter colonization. This remains a mystery: antibodies appear to be unimportant whereas CD4+ T‐cells essential. Finally, a viewpoint is given on whom should be immunized when a final vaccine becomes available.
Changes in Helicobacter pylori‐induced gastritis in the antrum and corpus during long‐term acid‐suppressive treatment in Japan
Authors: Uemura N. , Okamoto S. , Yamamoto S. , Matsumura N. , Yamaguchi S. , Mashiba H. , Sasaki N. , Taniyama K.
Published: March 2003

Background:

Several studies have shown that acid‐suppressive therapy aggravates corpus gastritis in patients with Helicobacter pylori infection, promoting the development of atrophic gastritis.

Aim:

To study the effects of long‐term use of antisecretory agents on the H. pylori‐positive gastric mucosa in Japan, a country with a high incidence of gastric cancer.

Methods:

A total of 141 H. pylori‐positive patients who had peptic ulcers or reflux oesophagitis were treated for 3 years with either omeprazole (20 mg/day) alone (n=7) or with omeprazole for primary therapy (8 weeks), followed by famotidine (40 mg/day) for maintenance therapy (n=134). Endoscopy was performed before, during, and after treatment. Biopsy specimens were taken from the greater curvature of the antrum and corpus and were examined histologically.

Results:

The long‐term use of famotidine after 8 weeks of treatment with omeprazole distinctly decreased H. pylori density and neutrophil infiltration in the antrum, but did not change H. pylori density in the corpus. The gastritis score increased in patients who had no, or only mild corpus gastritis before treatment (n=74), and significantly decreased in those who had moderate or severe gastritis before treatment (n=60). In four of the seven patients who received long‐term treatment with omeprazole alone, neutrophil infiltration and H. pylori density decreased not only in the antrum but also in the corpus. There was no increase in intestinal metaplasia or mucosal atrophy as assessed endoscopically during follow‐up.

Conclusion:

Changes in corpus gastritis in response to acid‐suppressive therapy depend on the severity of gastritis before treatment. Long‐term use of acid‐suppressive therapy apparently does not accelerate the development of atrophy or intestinal metaplasia in Japanese patients.
Lower‐dose 13C‐urea breath test to detect Helicobacter pylori infection—comparison between infrared spectrometer and mass spectrometry analysis
Authors: Sheu B.‐S. , Lee S.‐C. , Yang H.‐B. , Wu H.‐W. , Wu C.‐S. , Lin X.‐Z. , Wu J.‐J.
Published: March 2003

Background:

The expense of the 13C‐urea breath test (UBT) to detect Helicobacter pylori infection is mainly due to the cost of 13C‐urea and the analysis using isotope ratio mass spectrometry (IRMS).

Aim:

To test whether a UBT, using a lower dose of urea and lower‐priced isotope‐selective nondispersive infrared spectrometry (INIS), can preserve diagnostic efficacy in clinical practice.

Methods:

A total of 177 dyspeptic patients received endoscopy for H. pylori culture and histology. All of them received a UBT in which the duplicate baseline, 10 min, and 15 min breath samples after ingestion of 50 mg 13C‐urea were collected to analyse the excess 13CO2/12CO2 ratio (ECR) by IRMS (ABCA, Europa Scientific, UK) and INIS (UBiT‐IR200, Photal Otsuka Electronics, Japan), respectively.

Results:

Of the 177 patients, 84 were infected and 93 were uninfected with H. pylori. A close correlation of ECR was found between IRMS and INIS (r=0.9829 at 10 min; r=0.9918 at 15 min, P < 0.0001). Analysing the 15‐min samples, UBT by both IRMS and INIS achieved the same sensitivity (96.4%) and specificity (98.9%).

Conclusions:

INIS is as effective as IRMS for UBT, and can use a lower dose of 13C‐urea. This can provide an economic UBT, using the lower‐priced INIS and a low dose of 13C‐urea.
Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial
Authors: Kahrilas P. J. , Falk G. W. , Johnson D. A. , Schmitt C. , Collins D. W. , Whipple J. , D'Amico D. , Hamelin B. , Joelsson B. ,   FOR THE ESOMEPRAZOLE STUDY INVESTIGATORS
Published: March 2003

Background:

The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with acid‐related disease.

Methods:

1960 patients with endoscopy‐confirmed reflux oesophagitis (RO) were randomized to once daily esomeprazole 40 mg (n=654) or 20 mg (n=656), or omeprazole 20 mg (n=650), the standard recommended dose for RO, for up to 8 weeks in a US, multicentre, double‐blind trial. The primary efficacy variable was the proportion of patients healed at week 8. Secondary variables included healing and heartburn resolution at week 4, time to first resolution and sustained resolution of heartburn, and per cent of heartburn‐free days and nights. Safety and tolerability were also evaluated.

Results:

Significantly more patients were healed at week 8 with esomeprazole 40 mg (94.1%) and 20 mg (89.9%) vs. omeprazole 20 mg (86.9%), using cumulative life table estimates, ITT analysis (each P < 0.05). Esomeprazole 40 mg was also significantly more effective than omeprazole for healing at week 4 and for all secondary variables evaluating heartburn resolution. The most common adverse events in all treatment groups were headache, abdominal pain and diarrhoea.

Conclusion:

Esomeprazole was more effective than omeprazole in healing and symptom resolution in GERD patients with reflux oesophagitis, and had a tolerability profile comparable to that of omeprazole.
Triple therapy with clarithromycin, omeprazole, and amoxicillin for eradication of Helicobacter pylori in duodenal ulcer patients in Asia and Africa
Authors: Wong B. C. Y. , Chang F. Y. , Abid S. , Abbas Z. , Lin B. R. , Van Rensburg C. , Chen P. C. , Schneider H. , Simjee A. E. , Hamid S. S. , Seebaran A , Zhang J. , Destefano M. , Lam S. K.
Published: March 2003

Background:

Studies assessing the efficacy of triple therapy containing clarithromycin and amoxicillin for the eradication of Helicobacter pylori infection and healing of duodenal ulcers in Asian and African countries are limited.

Aim:

To determine the efficacy and safety of 1‐week triple therapy with omeprazole, amoxicillin and clarithromycin for eradicating H. pylori infection in patients with active duodenal ulcer living in Asian and African regions.

Methods:

This was an open‐label, multicentre study in 11 centres in Asia and Africa. Patients with endoscopy‐proven duodenal ulcer and who were H. pylori‐positive were treated with clarithromycin 500 mg, omeprazole 20 mg, and amoxicillin 1000 mg, all given twice daily for 7 days. Upper endoscopy was repeated at week 6 to check for ulcer healing and H. pylori status.

Results:

A total of 117 patients were recruited. H. pylori eradication rates were 85% by per protocol analysis and 80% by intention‐to‐treat analysis. Ulcer healing was found in 94% of subjects (per protocol analysis). Clinical success, measured by change of pre‐treatment ulcer symptoms, was strongly supported by complete resolution or improvement in 100% of the evaluable patients (per protocol analysis). Since treatment‐related adverse events, when present, were largely mild or moderate, the triple therapy regimen was considered safe.

Conclusion:

Seven‐day triple therapy with omeprazole, amoxicillin, and clarithromycin was efficacious for treating Asian and African patients with duodenal ulcer disease associated with H. pylori infection, and the treatment regimen was well‐tolerated.
Budesonide in the treatment of Crohn’s disease: a meta‐analysis
Authors: Papi C. , Luchetti R. , Gili L. , Montanti S. , Koch M. , Capurso L.
Published: March 2003

Aim:

To perform a meta‐analysis to assess the effectiveness and safety of oral budesonide for inducing remission in active Crohn’s disease and for preventing relapse in Crohn’s disease with medically‐ or surgically‐induced remission.

Methods:

All randomized, double‐blind controlled trials involving oral budesonide therapy in Crohn’s disease were retrieved from a Medline search, reviews articles or their bibliographies. Of 83 articles retrieved, 12 met the inclusion criteria. Data extraction was performed by three independent observers and scoring disagreements were resolved by consensus.

Results:

Six trials tested budesonide in active disease and six in quiescent disease. Budesonide was less effective than conventional corticosteroids for inducing remission of active Crohn’s disease (pooled rate difference, RD –8.5%; 95% CI: –16.4 to –0.7%; P=0.02), but corticosteroid‐related adverse events were reduced (RD –22.4%; 95% CI: –32 to –12.8%; P < 0.001). In quiescent Crohn’s disease, budesonide was as effective as placebo for preventing relapse in medically induced remission (RD –0.8%; 95% CI: –9.9 to 8.3%; P=0.42) and endoscopic recurrence in surgically induced remission (RD –3.5%; 95% CI: –16.9 to 9.8%; P=0.30). In the long term treatment, budesonide had an occurrence rate of corticosteroid‐related adverse effects similar to placebo (RD 5.3%; 95% CI: –3.9 to 14.5%; P=0.30).

Conclusions:

Budesonide is significantly less effective than conventional corticosteroids for inducing remission in active Crohn’s disease, but the risk of corticosteroid‐related adverse effects is significantly reduced. Budesonide is not effective in preventing relapse of Crohn’s disease after medically‐ or surgically‐induced remission.
Failure of a motilin receptor agonist (ABT‐229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric emptying: a randomized double‐blind placebo‐controlled trial
Authors: Talley N. J. , Verlinden M. , Snape W. , Beker J. A. , Ducrotte P. , Dettmer A. , Brinkhoff H. , Eaker E. , Ohning G. , Miner P. B , Mathias J. R , Fumagalli I. , Staessen D. , Mack R. J.
Published: March 2003

Introduction:

Motilin‐receptor agonists are prokinetics; whether they relieve the symptoms of functional dyspepsia is unknown. We aimed to test the efficacy of the motilin agonist ABT‐229 in functional dyspepsia patients with and without delayed gastric emptying.

Methods:

Patients were randomized with postprandial symptoms and documented functional dyspepsia by endoscopy (n=589 in intention‐to‐treat analysis). Patients were assigned to either the delayed or normal gastric emptying strata, based on a validated 13C octanoic acid breath test. Patients were then further randomized within each strata, to receive one of four doses of ABT‐229 (1.25, 2.5, 5 or 10 mg b.d. before breakfast and dinner) or placebo for 4 weeks, following a 2‐week baseline. The primary outcome was the assessment of change in symptom severity over the 2 weeks from baseline to final visit, based on a self‐report questionnaire measuring severity on visual analogue scales.

Results:

Baseline characteristics across the treatment arms were very similar. No significant differences in the upper abdominal discomfort severity score (maximum 800 mm) were observed for any active treatment arm vs. placebo (mean change from baseline −139, −141, −145, −160 and −134 mm for placebo, 1.25, 2.5, 5, and 10 mg, respectively, at 4 weeks by intention‐to‐treat). More patients on placebo reported a good or excellent global response than patients on 1.25 or 5 mg of active therapy (both P < 0.05). The results were very similar in those with and without delayed gastric emptying. Helicobacter pylori status did not predict response. Excluding patients with any baseline heartburn (total remaining n=240), ABT‐229 10 mg was inferior to placebo in relief of upper abdominal discomfort.

Conclusions:

ABT‐229 was of no value for relief of symptoms in functional dyspepsia, compared with placebo.
Factors associated with consulting medical or non‐medical practitioners for dyspepsia: an Australian population‐based study
Authors: Westbrook J. I. , Mcintosh J. , Talley N. J.
Published: March 2003

Background:

Little is known about how many dyspeptics in the population consult medical and non‐medical practitioners, or the factors associated with various consulting patterns.

Methods:

A cross‐sectional survey of 748 Australians with dyspepsia investigated their age, sex, dyspepsia symptoms, medical and non‐medical consultations, and health status on the SF‐12.

Results:

Overall, 56% had ever consulted a medical practitioner for dyspepsia. Of these, 54% consulted within 6 months of first symptoms. Non‐medical practitioners were consulted by 29%. Compared to dyspeptics in all, or most, other consulting groups, subjects who did not consult (37%, group NO) were characterized by fewer symptoms, better physical health, and younger age. Those who only consulted doctors (34%, group M) were older and had better mental, but poorer physical health. Those who only consulted non‐medical practitioners (7%, group N) were younger and had better physical, but poorer mental health. Dyspeptics consulting both medical and non‐medical practitioners (22%, group M + N), were older, more dissatisfied with medical care, had more symptoms and poorer physical and mental health. Timing of medical consultations was similar in groups M and M + N. Group M + N dyspeptics consulted similar types, but more non‐medical practitioners than group N. No sex differences were found in consulting behaviour.

Conclusions:

Many dyspeptics do not consult; they have fewer symptoms than consulters. Consultation with non‐medical practitioners is common and is associated with poor mental health. Dyspeptics seeking advice from both medical and non‐medical practitioners are less satisfied with their medical management than those who only consult doctors for their dyspepsia.
Review article: transcription factors and growth factors in ulcer healing
Authors: Szabo S. , Khomenko T. , Gombos Z. , Deng X. M. , Jadus M. R. , Yoshida M.
Published: March 2003

This review is focused on recent investigations demonstrating a pharmacological and patho‐physiologic role in gastroduodenal ulceration for growth factors such as basic fibroblast growth factor (bFGF), platelet‐derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), as well as for transcription factors. Our experiments revealed accelerated healing, without decreased gastric acid secretion, of chronic cysteamine‐induced duodenal ulcers in rats treated daily for 3 weeks with intragastric administration of bFGF, PDGF or VEGF. Our recent studies also indicate a pathophysiological role of endogenous growth factors in the natural history of experimental duodenal ulcer development and healing.

More recently, we investigated the genetic regulation of these growth factors in experimental duodenal ulceration. Since gene expression is most effectively controlled by transcription factors, proteins that bind tocis‐acting elements of DNA and guide the binding of polymerase II to start the transcription of specific mRNA, we tested the hypothesis that the expression of IEGs and their transcription factor products, such as Egr‐1 and Sp1, might precede the increased synthesis of bFGF, PDGF and VEGF in duodenal ulcer healing. Indeed, the duodenal ulcerogen cysteamine, but not its nonulcerogen and toxic analogue ethanolamine, rapidly increased duodenal (but not gastric) mucosal levels of ET‐1, which was followed by enhanced expression of Egr‐1 and a decrease in Sp1 in the preulcerogenic stage of duodenal ulceration. These changes in levels of ET‐1 and expression of transcription factors were also accompanied by increased expression of the CDK inhibitor p21. Thus, not only growth factors such as bFGF, PDGF and VEGF, but also transcription factors such as Egr‐1 and Sp1 and the cell cycle regulator p21, may play a role in the natural history of experimental duodenal ulceration.
Gastric epithelial cell proliferation and apoptosis in Helicobacter pylori‐infected mice
Authors: Yamaguchi T. , Nakajima N. , Kuwayama H. , Ito Y. , Iwasaki A. , Arakawa Y.
Published: March 2003

Background: Helicobacter pylori causes gastritis and is strongly associated with gastroduodenal ulcer and gastric cancer. The bacterium is associated with an increased rate of epithelial proliferation, which can be reversed by eradication of the organism. The mechanism of this response is not known, but this epithelial proliferation is one of the risk factors for developing gastric carcinoma. Recently, apoptosis also was found to be increased in the gastric mucosa of persons carrying H. pylori.

Methods: cagA‐positive H. pylori isolated from a human gastric ulcer was inoculated into BALB/C mice. At 4, 6, 12, 18 and 24 weeks, mice were injected with bromodeoxyuridine 5 mg/kg and killed 1 h later. Proliferation was analysed by histochemical staining for BrdU; apoptosis was examined by the TUNEL assay.

Results: The number of BrdU‐labelled cells in the antrum was significantly increased by H. pylori infection beginning 12 weeks after infection. The number of apoptotic cells in this tissue was increased significantly by 6 weeks after inoculation.

Conclusion: The proliferation observed in H. pylori infection may be a response to increased apoptosis.
Interactive roles of endogenous prostaglandin and nitric oxide in regulation of acid secretion by damaged rat stomachs
Authors: Takeuchi K. , Sugamoto S. , Yamamoto H. , Kawauchi S. , Tashima K.
Published: March 2003

Background: The acid inhibitory mechanism in the damaged stomach is known to involve endogenous nitric oxide (NO) as well as prostaglandin (PG).

Aim: To investigate the interaction between PG and NO in regulation of acid secretion in the stomach following damage.

Methods: Under urethane anaesthesia, a rat stomach was mounted in an ex vivo chamber and perfused with saline. Acid secretion, luminal PGE2, NO metabolites (NOx) and histamine output were measured before and after application of 20 m
m taurocholate Na (TC) for 30 min, with or without pre‐treatment with indomethacin and/or NG‐nitro‐
l‐arginine methyl ester (L‐NAME).

Results: Exposure of the stomach to TC caused a decrease in acid secretion, with concomitant increase of both luminal NOx and PGE2. Either L‐NAME or indomethacin reduced the decrease in acid secretion in response to TC, but only L‐NAME allowed acid secretion to increase over basal values. L‐NAME prevented the increase of luminal NOx after TC treatment, while indomethacin inhibited PGE2 release during and after exposure to TC. The increase in acid secretion in the presence of L‐NAME was prevented when indomethacin was given concomitantly. TC treatment increased histamine output in the lumen, a process that was enhanced by L‐NAME but reduced by indomethacin.

Conclusions: Damage to the stomach increases both NO and PG in the lumen, and decreases acid secretion. Inhibiting NO production increases acid secretion in the damaged stomach, but only when PG biosynthesis is intact. It is assumed that endogenous PG has a dual role in the regulation of acid secretion in the damaged stomach: an inhibitory effect at the parietal cell and an excitatory effect probably through enhancing the release of mucosal histamine.
Helicobacter pylori screening for individuals requiring chronic NSAID therapy: a decision analysis
Authors: Scheiman J. M. , Bandekar R. R. , Chernew M. E. , Fendrick A. M.
Published: March 2003

Introduction:

Although it is incontrovertible that Helicobacter pylori causes peptic ulcer disease, controversy persists regarding the impact of H. pylori infection on the incidence of NSAID‐related complications and whether H. pylori eradication reduces the rate of adverse events.

Methods:

A symptom‐driven decision analytic model was developed to compare the clinical and economic impact of H. pylori screening compared to a strategy of no H. pylori testing for individuals requiring chronic NSAID therapy. In the principal analysis, it was assumed that untreated H. pylori infection increased the ulcer risk by 50% and that successful eradication reduced the risk of adverse events to that of uninfected patients. Patients’ ulcer risk and the protective effect of H. pylori eradication were evaluated using sensitivity analysis.

Results:

When compared to no H. pylori testing, H. pylori screening led to fewer symptomatic ulcers (no test, 5.4; H. pylori test, 4.6 per 100 patient years) and ulcer complications (no test, 2.6; H. pylori test, 2.3 per 100 patient years) and a higher cost per patient (no test, $435; H. pylori test, $556). The incremental cost attributable to the H. pylori screening strategy to prevent a symptomatic and complicated ulcer was $16 805 and $31 842, respectively. The clinical and cost‐effectiveness advantage of H. pylori screening improved as patients’ ulcer risk increased or the protective effect of H. pylori eradication was enhanced.

Conclusions:

Based upon the available evidence, H. pylori screening has the potential to reduce NSAID‐related adverse events for average‐risk patients at an incremental cost. Until controlled investigations definitively quantify the effect of H. pylori eradication on clinically significant NSAID‐related adverse events, a compelling argument can be made for H. pylori testing for chronic NSAID users at increased risk of ulcer disease.
Randomized trial of low‐dose misoprostol and naproxen vs. nabumetone to prevent recurrent upper gastrointestinal haemorrhage in users of non‐steroidal anti‐inflammatory drugs
Authors: Chan F. K. L. , Sung J. J. Y. , Ching J. Y. L. , Wu J. C. Y. , Lee Y. T. , Leung W. K. , Hui Y. , Chan L. Y. , Lai A. C. W. , Chung S. C. S.
Published: March 2003

Background:

Prophylactic misoprostol or non‐steroidal anti‐inflammatory drugs (NSAIDs) with low gastric toxicity (nabumetone) has been shown to reduce mucosal injury.

Aim:

To compare nabumetone vs. co‐therapy of naproxen with low‐dose misoprostol for secondary prevention of upper gastrointestinal bleeding in NSAID users.

Methods:

NSAID users presenting with upper gastrointestinal bleeding were enrolled if they required long‐term NSAIDs. After ulcer healing, they were randomized to receive: naproxen (500–1000 mg/day) and misoprostol (200 μg b.d.), or nabumetone (1000–1500 mg/day) and placebo misoprostol for 24 weeks. The primary end‐point was recurrent upper gastrointestinal bleeding. The secondary end‐point was the proportion of patients suffering from major gastrointestinal events including ulcer bleeding, symptomatic ulcers and severe dyspepsia.

Results:

A total of 90 patients were included in the intention‐to‐treat analysis (misoprostol/naproxen 45, nabumetone 45). Recurrent bleeding occurred in 10 patients (22.2%) receiving misoprostol/naproxen compared with three (6.7%) receiving nabumetone (relative risk 3.33, 95% CI: 0.98–11.32, P=0.069). The proportion of patients suffering from major gastrointestinal events at 24 weeks was 31.1% in the misoprostol/naproxen group and 28.9% in the nabumetone group.

Conclusions:

Misoprostol/naproxen is not superior to nabumetone for secondary prevention of upper gastrointestinal bleeding. Neither low‐dose misoprostol nor nabumetone is adequate for high‐risk NSAID users.
Oral hypoglycaemic drugs and gastrointestinal symptoms in diabetes mellitus
Authors: Bytzer P. , Talley N. J. , Jones M. P. , Horowitz M.
Published: March 2003

Background:

Gastrointestinal symptoms are commonly reported as side‐effects of oral hypoglycaemic drugs. It may be very difficult to distinguish between spontaneous and truly drug‐related symptoms due to the high background incidence of gastrointestinal symptoms. Gastrointestinal symptoms in diabetic patients have also been linked to factors associated with long‐standing disease and suboptimal control.

Aim:

To explore the association between gastrointestinal symptoms and treatment with oral hypoglycaemic drugs in a large cohort of subjects with type 2 diabetes.

Patients and methods:

956 subjects with type 2 diabetes participated in the study. All subjects completed a validated, self‐administered questionnaire on gastrointestinal symptoms, diabetes, drug use and various potential risk factors for gastrointestinal symptoms. The association between oral hypoglycaemics and nine gastrointestinal symptom groups was assessed based on logistic regression.

Results:

405 of the 956 patients used oral hypoglycaemic drugs. Metformin use was independently associated with chronic diarrhoea (odds ratio 3.08, 95% CI: 1.29–7.36, P < 0.02) and with faecal incontinence (odds ratio 1.95, 95% CI: 1.10–3.47, P < 0.05). Use of sulphonylureas was associated with less abdominal pain, but not with any other gastrointestinal symptom.

Conclusions:

Troublesome gastrointestinal symptoms do not appear to be caused by oral hypoglycaemics, except for diarrhoea and faecal incontinence, which are strongly and independently associated with metformin use.
The effect of oral administration of Lactobacillus GG on antibiotic‐associated gastrointestinal side‐effects during Helicobacter pylori eradication therapy
Authors: Armuzzi A. , Cremonini F. , Bartolozzi F. , Canducci F. , Candelli M. , Ojetti V. , Cammarota G. , Anti M. , De Lorenzo A. , Pola P. , Gasbarrini G. , Gasbarrini A.
Published: March 2003

Background:

One‐week triple therapy is currently considered the golden standard against Helicobacter pylori. However, gastrointestinal side‐effects are among the major pitfalls in such regimens. Probiotic supplementation might help to prevent or reduce such drug‐related manifestations.

Aim:

To determine whether adding the probiotic Lactobacillus GG to an anti‐H. pylori regimen could help to prevent or minimize the gastrointestinal side‐effects burden.

Methods:

Sixty healthy asymptomatic subjects screened positive for H. pylori infection were randomized to 1 week rabeprazole (20 mg b.d.), clarithromycin (500 mg b.d.), tinidazole (500 b.d.) and the probiotic Lactobacillus GG for 14 days or to the same regimen with a placebo preparation. Patients completed validated questionnaires during the week of treatment and during the following 3 weeks, to determine the type and severity of side‐effects and an overall judgement of tolerability.

Results:

Diarrhoea, nausea and taste disturbance were significantly reduced in the Lactobacillus GG supplemented group (relative risk=0.1, 95% CI: 0.1–0.9; relative risk=0.3, 95% CI: 0.1–0.9; relative risk=0.5, 95% CI: 0.2–0.9, respectively). An overall assessment of treatment tolerability showed a significant difference in favour of the Lactobacillus GG supplemented group (P=0.04).

Conclusions:

Lactobacillus GG supplementation showed a positive impact on H. pylori therapy‐related side‐effects and on overall treatment tolerability.