bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: rabeprazole’s tolerability profile in clinical trials
Authors: Thjodleifsson  , Cockburn
Published: March 2003

Rabeprazole is a new member of a class of substituted benzimidazole drugs known as proton pump inhibitors. Comparative trials have demonstrated that it is at least as effective as omeprazole for the treatment of gastro‐oesophageal reflux disease (GERD), duodenal ulcers, or gastric ulcers. It is significantly more effective than histamine2‐receptor antagonists for acid suppression, GERD healing and pain relief, and duodenal ulcer healing and pain relief. Adverse events reported during clinical trials provide an important indication of a medication’s tolerability. We demonstrate that rabeprazole has a favourable adverse events profile. It is well tolerated in placebo‐controlled studies and comparative trials with omeprazole and H2‐receptor antagonists. Moreover, no dose adjustments are required for special populations, such as the elderly or patients with renal or mild‐to‐moderate hepatic disease. Adverse events data from clinical trials support the use of rabeprazole as a treatment for acid‐related diseases.
Anti‐diarrhoeal effects of seirogan in the rat small intestine and colon examined in vitro
Authors: MEERVELD B. GREENWOOD‐VAN , TYLER  , KUGE  , OGATA
Published: March 2003

Background:

Seirogan is a beechwood extract composed of guaiacol, creosol and other related phenolic compounds which is widely used as an anti‐diarrhoeal agent in Asia. Abnormalities in water and electrolyte transport are often the cause of diarrhoea, but the mechanism of action of seirogan on small intestinal and colonic mucosal ion transport is unknown.

Aim:

To examine the effect of seirogan on electrogenic ion transport in vitro.

Methods:

Sheets of rat jejunum and colon were mounted in Ussing chambers, and transmural potential difference (PD) was used as an electrical marker of changes in mucosal ion transport. Hypersecretory conditions were induced by acetylcholine (ACh).

Results:

Serosal or mucosal application of seirogan (0.1–100 μg/mL) decreased basal jejunal transmural PD. Pre‐treatment of the tissue with the neurotoxin, tetrodotoxin, did not inhibit the seirogan‐induced changes in basal electrical activity. Seirogan had no effect on basal transmural PD in the ileum and colon. Under ACh‐induced hypersecretory conditions in the small intestine and colon, addition of serosal or mucosal seirogan produced antisecretory effects determined indirectly by measurement of transmural PD.

Conclusion:

The ability of seirogan to decrease basal transmural PD in the jejunum, and inhibit the ACh‐induced electrical responses, may contribute to its anti‐diarrhoeal action.
Review article: coeliac disease and its management
Authors: PARNELL  , CICLITIRA
Published: March 2003

Coeliac disease (CD) is a disorder of the small intestine, characterized by villous atrophy, due to an intolerance to dietary gluten in genetically susceptible individuals, which responds to gluten withdrawal. The underlying immunological mechanisms causing the disorder are still being worked out.

In recent years a wide range of clinical presentations has become increasingly apparent, as has a lengthening list of associated conditions. Severe malabsorption with steatorrhoea and profound weight loss is seen infrequently, perhaps as a result of earlier diagnosis and the recognition of ‘silent’ and ‘latent’ disease.

The prevalence of CD as judged by population screening with, in particular, anti‐endomysial antibodies, appears to be much higher than that found with clinically apparent cases.

There are a variety of well recognized complications, the commonest probably being osteopenia and osteoporosis. The marked increased risk of lymphoma can be avoided by a strict gluten‐free diet.

Follow‐up of patients needs to be lifelong with prompt investigation of new symptoms and blood test abnormalities.
Protection of human gastric mucosa against aspirin—enteric coating or dose reduction?
Authors: Cole  , Hudson  , Liew  , Murray  , Hawkey  , Heptinstall
Published: March 2003

Background:

Aspirin is widely used for cardiovascular prophylaxis.

Aim:

To compare the effectiveness of two widely‐used strategies—dose reduction and enteric coating—for the minimization of gastric mucosal injury or toxicity.

Methods:

Twelve healthy volunteers were studied. On four separate occasions each received, under blinded conditions, five daily doses of plain aspirin 300 mg, plain aspirin 75 mg, enteric‐coated aspirin 300 mg or placebo. Ex vivo prostaglandin E2 synthesis was stimulated by the vortex mixing of gastric mucosal biopsies in Tris saline and measured by radioimmunoassay. Mucosal injury was quantified both by counting erosions and with a visual analogue scale.

Results:

All three preparations reduced prostaglandin E2 synthesis by day five, by (median) 84% for plain aspirin 300 mg, by 80% for enteric coated aspirin 300 mg and by 63% for plain aspirin 75 mg. There was little mucosal injury prior to the start of each dose and period and no significant change with placebo. Plain aspirin caused a dose‐dependent mucosal injury, with two (median, IQR 0–7) gastric erosions after five days of plain aspirin 75 mg, and 18 (2–26) after five days of plain aspirin 300 mg. With enteric‐coated aspirin 300 mg there were 0 (0–1) gastric erosions (P = 0.003 compared to plain aspirin 300 mg P = 0.11, compared to plain aspirin 75 mg).

Conclusion:

Enteric coated aspirin reduces acute gastric mucosal injury to placebo levels, despite its inhibition of prostaglandin synthesis. Enteric coating is an appropriate strategy for the prevention of gastric mucosal damage induced by low‐dose aspirin, which warrants systematic clinical evaluation.
Depletion of colonic detoxication enzyme activity in mice with dextran sulphate sodium‐induced colitis
Authors: CLAPPER  , ADRIAN  , PFEIFFER  , KIDO  , EVERLEY  , COOPER  , MURTHY
Published: March 2003

Background

: The increased risk of colonic malignancies in individuals with ulcerative colitis has prompted a search for early biomarkers of disease progression.

Aim

: To characterize Phase II detoxication enzyme expression during acute and chronic colitis. The mouse model of dextran sulphate sodium (DSS)‐induced colitis represents a relevant system with which to sequentially evaluate the spectrum of biochemical changes associated with colorectal cancer risk.

Methods

: Acute and chronic colitis were induced in Swiss Webster mice by administering DSS in the drinking water (5%) for 1–4 cycles. Each cycle consisted of 7 days DSS and 14 days of water. The glutathione S‐transferase (GST) activity, γ‐glutamylcysteine synthetase (γ‐GCS) activity and glutathione content of the colonic tissues were determined at various time points throughout the experiment. Alterations in GST isozyme expression were confirmed by Western and Northern blot.

Results

: GST activity was reduced significantly in the colon by the end of Cycle 1 (84% of control values). Specific activities continued to decrease with subsequent cycles of DSS exposure. By the end of Cycle 4, glutathione levels and γ‐GCS activity had reached 29% and 56% of control, respectively.

Conclusions

: These data suggest that detoxication enzyme depletion is associated with both acute and chronic colitis and may be an important event in the progression of ulcerative colitis to colon cancer.
High cure rate of Helicobacter pylori infection using tripotassium dicitrato bismuthate, furazolidone and clarithromycin triple therapy for 1 week
Authors: XIAO  , LIU  , HU  , XIA  , TYTGAT
Published: March 2003

Background:

When metronidazole is used in bismuth‐based or proton pump inhibitor‐based triple therapy, the cure rate of Helicobacter pylori is usually high. However, metronidazole‐resistant H. pylori strains, which are increasing in frequency, are a major cause of failed H.␣pylori eradication.

Aim:

To evaluate the efficacy of non‐metronidazole containing bismuth‐based triple therapy for H. pylori infection.

Methods:

One‐hundred and eighty H. pylori‐positive patients with endoscopically documented peptic ulcer disease or functional dyspepsia were randomly assigned to one of three 1‐week regimens containing tripotassium dicitrato bismuthate (also called colloidal bismuth subcitrate) 240 mg b.d. and two antibiotics: furazolidone 100 mg b.d. plus clarithromycin 250 mg b.d. (Group A); or clarithromycin 250 mg b.d. plus amoxycillin 1000 mg b.d. (Group B); or furazolidone 100 mg b.d. plus josamycin 1000 mg b.d. (Group C). H. pylori status was assessed by rapid urease test, histology and culture of gastric biopsy specimens taken from both the antrum and corpus, both before and at least 4 weeks after completion of therapy.

Results:

Thirteen patients dropped out (3 in group A, 5 in group B and 5 in group C). Based on an intention‐to‐treat analysis, the eradication rates achieved in groups A, B and C were 88% (53/60), 58% (35/60) and 77% (46/60), respectively. These differences were significant between groups A and B (P < 0.001), as well as between groups B and C (P < 0.05). Side‐effects occurred in 7 (12%) patients in group A, 3 (5%) in group B and 8 (13%) in group C, and were mild, with the exception of vomiting in one patient (group C) that resulted in withdrawal from the study.

Conclusion:

One‐week triple therapy, consisting of tripotassium dicitrato bismuthate, low‐dose furazolidone and low‐dose clarithromycin, achieves a high cure rate of H. pylori.
Alendronate gastric ulcers
Authors: GRAHAM  , MALATY
Published: March 2003

Background

: It appears likely that drugs other than NSAIDs may cause ulcers and ulcer complications (e.g. potassium chloride). Alendronate (Fosamax) is used in the treatment and prevention of metabolic bone disease and has also been associated with severe oesophageal damage and stricture. We have previously shown that the dose of alendronate used for Paget's disease (40 mg) causes gastric damage similar to NSAIDs. The usual dose for the treatment of postmenopausal osteoporosis is 10 mg per day.

Aim

: To investigate whether the 10 mg dose of alendronate causes gastric ulcers.

Methods

: We performed an endoscopist‐blind, crossover, randomized, single‐centre comparison of 10 mg of alendronate/day and placebo in volunteers aged 40 years or more. Video‐endoscopy was used to evaluate the presence and degree of mucosal damage to the oesophagus, stomach, or duodenal bulb after 7 and 14 days of treatment.

Results

: Twenty‐four healthy volunteers participated, including 15 women and nine men, ranging in age from 41 to 52 years. Visible gastric mucosal damage was present in nine (38%) who received alendronate compared to three (13%) in the placebo group. There was a marked difference in the severity of mucosal damage; there were no ulcers or large erosions in those receiving placebo. In contrast, potentially clinically significant gastric mucosal injury was seen in six subjects receiving alendronate (two developed antral ulcers and four had large (4–8 mm) superficial antral erosions) compared to none in the placebo group (P = 0.0219). One subject developed oesophageal damage in the form of multiple linear superficial erosions in the mid and distal oesophagus. Duodenal injury was not seen.

Conclusion

: Alendronate causes gastric ulceration, suggesting that alendronate use may be associated with ulcer complications such as acute upper gastrointestinal bleeding. The results of this study suggest the need for post‐marketing surveillance to clarify the nature, frequency and magnitude of any potential gastrointestinal side‐effects associated with the use of this drug.
Effects of extracellular pH on restitution and proliferation of rabbit oesophageal epithelial cells
Authors: JIMENEZ  , LANAS  , PIAZUELO  , ESTEVA
Published: March 2003

Background and Aims

: Exposure to luminal acid induces mucosal damage in the oesophagus. The extent and degree of interaction of acid with wound repair mechanisms of the oesophagus have not been explored.

Methods

: Rabbit oesophageal cells were isolated, cultured and exposed to different extracellular pHs for several periods of time. Cell mortality was studied in both isolated and primary cultures of these cells by cell flow cytometry using fluorochrome propidium iodide and LDH release. Subconfluent cell cultures were used to study proliferative responses determined by [3H]‐thymidine incorporation into DNA. Restitution was studied in confluent monolayers wounded by mechanical denudation.

Results

: Isolated cells were resistant to acid when exposed to pH > 2 for 15 min. Cell proliferation increased with small pH decreases (7–6.5) if the period of exposure was less than 6 h, but was inhibited with lower pHs and/or longer periods of acid exposure. However, restitution was gradually inhibited with further pH decreases (6.5–3) and time of acid exposure (0.5–24 h).

Conclusions

: The wound repair activities of oesophageal epithelial cells are deeply affected by even small decreases in pH. These findings may help to explain the need for profound acid inhibition in acid‐related reflux oesophagitis.
Furazolidone‐containing short‐term triple therapies are effective in the treatment of Helicobacter pylori infection
Authors: LIU  , XIAO  , SHI  , WU  , ZHANG  , XU  , TYTGAT
Published: March 2003

Background

: A furazolidone‐containing therapeutic regimen for Helicobacter pylori infection has attracted special interest in the face of a rising world‐wide metronidazole resistant H. pylori, and the expense of currently used antimicrobial regimens.

Aim

: To evaluate the efficacy of furazolidone‐containing regimens in eradicating H. pylori.

Methods

: One‐hundred and forty H. pylori positive patients with endoscopically confirmed duodenal ulcer or functional dyspepsia received one of four different regimens to eradicate H. pylori. In the first trial, the patients were randomly assigned to receive a 1‐week course of furazolidone 100 mg b.d. and clarithromycin 250 mg b.d., with either tripotassium dicitrato bismuthate (TDB) 240 mg b.d. (FCB group) or lansoprazole 30 mg daily (FCL group). In the second trial, the patients were randomly assigned to receive a 1‐week course of clarithromycin 250 mg b.d. and omeprazole 20 mg daily, with either furazolidone 100 mg b.d. (FCO group) or metronidazole 400 mg b.d. (MCO group). Endoscopy was repeated 4 weeks following completion of therapy with re‐assessment of H. pylori status on gastric biopsies by histology and culture.

Results

: Four patients (1 in FCB, 1 in FCO and 2 in MCO groups) dropped out because they refused a follow‐up endoscopy. Eradication rates of H. pylori on an intention‐to‐treat basis in the FCB, FCL, FCO and MCO groups were 91% (32/35, 95% CI: 82–99%), 91% (32/35, CI: 82–99%), 86% (30/35, CI: 74–97%) and 74% (26/35, CI: 60–89%) (all P > 0.05), respectively. Mild side‐effects occurred in 15% of the 140 patients. In MCO group, the eradication rate in the patients infected with metronidazole‐sensitive isolates of H. pylori was 86%, but dropped to 67% in those with metronidazole‐resistance strains (P = 0.198).

Conclusion

: One‐week regimens containing furazolidone and clarithromycin in combination with TDB or a proton pump inhibitor fulfil the criteria for successful H. pylori therapy.
The optimal antibiotic combination in a 5‐day Helicobacter pylori eradication regimen
Authors: NEVILLE  , EVERETT  , LANGWORTHY  , TOMPKINS  , MAPSTONE  , AXON  , MOAYYEDI
Published: March 2003

Background

: Current guidelines for Helicobacter pylori eradication recommend 7 days of a proton‐pump inhibitor, clarithromycin (C), and either metronidazole (M) or amoxycillin (A). A shorter course would be cheaper and could be as effective.

Aim

: This study was designed to investigate the efficacy of three 5‐day regimens based on lansoprazole (L).

Methods

: 168 dyspepsia patients with H. pylori infection were randomized to receive a 5‐day course of either LCM, LAC or CALM, and a 13C‐urea breath test was performed after 4 weeks to assess eradication.

Results

: 160 patients completed the study. Intention‐to‐treat eradication rates were as follows: LCM 81%, LAC 59%, CALM 88%. LCM and CALM gave significantly better eradication rates than LAC. There was no significant difference in adverse events across the three groups. Logistical regression analysis showed that the specific regimen used and the age of the patient were the only factors influencing eradication outcome.

Conclusions

: Five days of CALM yields acceptable eradication rates, and is cheaper than conventional 7‐day proton pump inhibitor‐triple therapy. It appears to offer good results in metronidazole‐resistant strains of H. pylori. A randomized trial comparing 5‐day CALM with conventional 7‐day therapy is needed before this regimen can be recommended for routine use.
An evaluation of increasing doses of ranitidine for treatment of heartburn
Authors: PAPPA  , BUARON  , PAYNE  , SIRGO  , GIEFER
Published: March 2003

Background

: This was a randomized, double‐blind, placebo‐controlled, multicentre, parallel group, dose‐ranging trial of ranitidine tablets for relief of episodic heartburn. Adult out‐patients who reported heartburn relieved by antacids at least seven times per week were eligible.

Methods

: Patients who successfully completed a 1‐week single‐blind placebo run‐in phase and who did not achieve adequate relief in more than 50% of heartburn episodes were randomized to a 1‐week, double‐blind treatment phase during which they received ranitidine doses of 25, 75 or 125 mg, or placebo.

Results

: Of 577 patients randomized, 566 had at least one evaluable heartburn episode and were included in the intention‐to‐treat analysis. All three ranitidine doses were statistically significantly superior to placebo in providing overall episodic heartburn relief for the first episode (P < 0.002), last episode (P≤0.004), and all episodes combined (P <  0.001). The ranitidine 75 mg and 125 mg doses provided sustained relief (relief within 60 min of dosing that lasted throughout the 4‐h evaluation period) to a greater proportion of patients for each individual episode (43–56% for 75 mg and 42–57% for 125 mg) than the ranitidine 25 mg dose (35–50%) or placebo (21–29%). The incidence of adverse events was similar in all treatment groups.

Conclusions

: All three ranitidine doses (125, 75 and 25 mg) are safe and superior to placebo in providing adequate relief for heartburn. Ranitidine's onset of relief was progressive and clearly present by 30 min as shown by statistically significant differences for the 75 mg dose when compared to placebo. Similarly, patients treated with ranitidine 75 mg and 125 mg consumed statistically fewer rescue antacids than placebo‐treated patients for the first episode. All three doses were well tolerated, with adverse event profiles similar to those of placebo.
The effect of Helicobacter pylori eradication on intragastric pH during dosing with lansoprazole or ranitidine
Authors: Herwaarden M. A. van , Samsom M. , Nispen C. H. M. van , Mulder P. G. H. , Smout A. J. P. M.
Published: March 2003

Background

: The antisecretory effect of omeprazole on intragastric pH is decreased in the absence of Helicobacter pylori.

Aim

: To investigate the effect of H. pylori eradication on intragastric pH during lansoprazole or ranitidine dosing in 41 asymptomatic H. pylori‐positive subjects.

Method

: Two groups of healthy H. pylori‐positive volunteers were investigated. One group was dosed with lansoprazole 30 mg at 08.00 hours for at least 8 days, before and after 2 weeks of placebo‐controlled double‐blind eradication therapy using ranitidine bismuth citrate 400 mg b.d. and clarithromycin 500 mg b.d. The other group was dosed with ranitidine 300 mg at 23.00 hours for at least 8 days using the same trial design. An upper endoscopy was performed to establish H. pylori status by rapid urease test, culture and histology before both periods of dosing. Twenty‐four hour intragastric pH recording was performed on the final day of all periods of dosing.

Results

: H. pylori eradication significantly decreased the intragastric pH reached during lansoprazole treatment throughout all periods of the day. Intragastric pH during ranitidine treatment was not affected by H. pylori eradication, except for the late‐night period.

Conclusion

: H. pylori eradication has a more pronounced effect on the acid‐inhibiting properties of lansoprazole than on those of ranitidine.
Gastrointestinal safety and tolerance of ibuprofen at maximum over‐the‐counter dose
Authors: Doyle  , Furey  , Berlin  , Cooper  , Jayawardena  , Ashraf  , Baird
Published: March 2003

Background

:  Delineation of non‐steroidal anti‐inflammatory drug (NSAID) gastrointestinal toxicity has largely depended on retrospective epidemiologic studies which demonstrate that lower doses of NSAIDs pose a lower risk of gastrointestinal toxicity. Ibuprofen, a propionic acid NSAID, has, in most such studies, exhibited a favourable profile in terms of gastrointestinal bleeding. Since 1984, ibuprofen has been available as a non‐prescription analgesic/antipyretic with a limit of 1200 mg/day for 10 days of continuous use. Trials and spontaneously reported adverse experiences suggest that gastrointestinal symptoms and bleeding are rare.

Methods

: This study prospectively evaluated the gastrointestinal tolerability, as compared to placebo, of the maximum non‐prescription dose and duration of ibuprofen use in healthy subjects representative of a non‐prescription analgesic user population.

Results

: Gastrointestinal adverse experiences were similar in the placebo and ibuprofen groups (67 out of 413, 16% with placebo vs. 161 out of 833, 19% with ibuprofen). There was no difference between the two groups in the proportion discontinuing due to a gastrointestinal event. Gastrointestinal adverse experiences reported by ≥ 1% of subjects were: dyspepsia, abdominal pain, nausea, diarrhoea, flatulence, and constipation. Seventeen (1.4%) subjects had positive occult blood tests: their frequency was comparable between treatments.

Conclusions

: When used as directed to treat episodic pain, non‐prescription ibuprofen at the maximum dose of 1200 mg/day for 10 days, is well‐tolerated.
Omeprazole therapy decreases the need for dilatation of peptic oesophageal strictures
Authors: Barbezat  , Schlup  , Lubcke
Published: March 2003

Background

: Better control of gastric acid secretion with omeprazole appeared to decrease the need for dilatation of oesophageal strictures complicating gastro‐oesophageal reflux disease in our hospital‐based endoscopy service.

Aim

: To investigate whether the perceived decrease in the need for oesophageal dilatation could be documented from endoscopy records, and, if confirmed, whether this could be related to the treatment used.

Patients and methods

: Retrospective study of the records of 69 patients who had peptic oesophageal strictures dilated, followed by treatment with acid inhibition for at least 6 months. Mean duration of follow‐up was 3.9 years during treatment with H2‐receptor antagonists and 2.1 years while on omeprazole (258 and 78 patient‐years, respectively). Re‐dilatation rates were compared between those treated with H2‐receptor antagonists or omeprazole.

Results

: There has been a significant decrease in dilatations performed for gastro‐oesophageal reflux induced strictures (P < 0.001), while dilatation rates for other indications remained constant. Treatment with omeprazole not only decreased the need for further dilatations, but also prolonged the mean time between any further dilatations to 26.3 months compared to 9.3 months for those on an H2‐receptor antagonist (P < 0.0001).

Conclusions

: Following dilatation of peptic oesophageal strictures, treatment with omeprazole in place of an H2‐blocker significantly decreases the need for repeat dilatation.
Safety and efficacy of nabumetone in osteoarthritis: emphasis on gastrointestinal safety
Authors: Scott  , Palmer
Published: March 2003

Aim:

To compare the efficacy and gastrointestinal (GI) safety of nabumetone with two comparator non‐steroidal anti‐inflammatory drugs (NSAIDs), diclofenac SR and piroxicam.

Methods:

Two randomized, double‐blind, multicentre, parallel group trials were carried out in patients with moderate to severe osteoarthritis of the hip or knee. During the 6 month treatment phase, the safety and efficacy of nabumetone (1500–2000 mg/day) was compared to diclofenac SR (100 mg/day) or piroxicam (20–30 mg/day). GI safety was evaluated by reviewing all adverse events reported during the trials and presenting all cases of ulcers (complicated and uncomplicated), as well as other bleeding events that may have been associated with NSAID administration.

Results:

Most of the efficacy parameters showed no significant differences between the NSAIDs, although diclofenac SR was significantly better than nabumetone in one of 18 efficacy parameters. Nabumetone‐treated patients experienced significantly fewer ulcer and bleeding events compared to patients treated with the comparator NSAIDs [1.1% (4/348) vs. 4.3% (15/346), P= 0.01]. Bleeding events, including outright upper or lower GI bleeding or a significant decline in haemoglobin, occurred in significantly fewer patients treated with nabumetone than with the comparator NSAIDs [1.1% (4/348) vs. 3.5% (12/346), P < 0.05]. More importantly, complications associated with either ulcers (perforation) or bleeding (leading to hospitalization or withdrawal) occurred in significantly fewer patients receiving nabumetone [0% (0/348)] than with comparator NSAIDs [1.4% (5/346), (P < 0.05)].

Conclusion:

The results suggest that nabumetone was similar in efficacy by most criteria to diclofenac SR and piroxicam in relieving the symptoms of osteoarthritis; however, nabumetone’s GI safety profile was generally superior to that of both comparator NSAIDs. In the pooled analysis, nabumetone was associated with a significantly lower total incidence of ulcers and bleeding events, and a significantly lower incidence of complications associated with these events.
Review article: the initial management of uninvestigated dyspepsia in younger patients—the value of symptom‐guided strategies should be reconsidered
Authors: Hession  , Malagelada
Published: March 2003

Several major management guidelines on dyspepsia (upper abdominal pain or discomfort) recommend an initial ‘test‐and‐treat’ policy (non‐invasive Helicobacter pylori testing with eradication therapy if positive) in uninvestigated patients less than about 45 years old. However, the evidence that this is the optimal strategy is limited. Data from the few available randomized controlled trials provide evidence that this policy improves symptomatology more than a ‘test‐and‐endoscope’ approach (in which only H. pylori‐positive patients undergo early endoscopy) in those with upper abdominal pain. The balance of cost‐effectiveness data from clinical studies and decision analyses indicates that both ‘test‐and‐treat’ and empirical anti‐secretory therapy approaches are more cost‐effective than the ‘test‐and‐endoscope’ strategy. Therefore, given concerns about the safety of widespread H. pylori eradication, initial empirical anti‐secretory therapy may be a cost‐effective alternative to the ‘test‐and‐treat’ policy in some younger dyspeptic patients. The effectiveness of such an empirical approach might well be improved by symptom‐guided therapy and there is growing evidence that the predominant dyspeptic symptom may provide this guide. The diagnostic, therapeutic and economic utility of this approach merits further clinical investigation.
Personal review: alarmism or legitimate concerns about long‐term suppression of gastric acid secretion?
Authors: Yeomans  , Dent
Published: March 2003

This article responds to controversial issues about the long‐term use of acid suppression raised in a recent article in this journal by Waldum & Brenna. Although rebound acid secretion occurs following proton pump inhibitor therapy, the clinical significance of this is unclear, but the proposal that this is a major driver of acid‐related diseases is considered implausible. The polypoid deformity of the gastric corpus that can occur with long‐term proton pump inhibitor therapy is not neoplastic, and therefore has no bearing on other issues raised about proton pump inhibitor therapy and gastric malignancy. Current data in humans suggest that the magnitude of serum gastrin elevation from proton pump inhibitor treatment of up to 10 years, and any theoretical risks from this, have been overstated by Waldum & Brenna. Pernicious anaemia is a model of very doubtful validity for the risks of proton pump inhibitor therapy on several grounds. The proposal that diffuse gastric carcinoma arises from acid suppression‐induced stimulation of enterochromaffin‐like cells is challenged vigorously, because this is based on an implausible and substantially criticized interpretation of histopathology. It is agreed that it is appropriate to be cautious about the safety of long‐term acid suppression, because no data are available for lifelong treatment in humans. Such caution should be tempered by a critical assessment of the benefits of this treatment in relation to any possible risks. The substantial data that now exist from long‐term treatment of humans with proton pump inhibitors has not thus far revealed any definite risks. The risk of death from anti‐reflux surgery, although small, would seem to far exceed any possible risks associated with long‐term proton pump inhibitor use. Available data suggest that denial of the benefits of effective acid suppressant therapy to patients with clear‐cut troublesome acid related disorders is an overreaction to concerns about the biological effects of inhibiting acid secretion with proton pump inhibitors.
Equally high efficacy of 4, 7 and 10‐day triple therapies to eradicate Helicobacter pylori infection in patients with ulcer disease
Authors: Hurenkamp G. J. B. , Van Der Ende A. , Grundmeijer H. G. L. M. , Tytgat G. N. J. , Van Der Hulst R. W. M.
Published: March 2003

Background:

In patients with ulcer disease the optimal dose and duration of Helicobacter pylori treatment containing omeprazole (O), metronidazole (M) and clarithromycin (C) has yet to be established. The efficacy might be influenced by metronidazole‐ and clarithromycin‐resistance.

Aim:

To study the effect of duration of OMC treatment on its efficacy and influence of metronidazole‐resistance and clarithromycin‐resistance on the optimal duration.

Materials and methods:

Ulcer patients (n=76) were randomized to three double‐blind treatments of 10 days: OMC 4 consisted of 4 days b.d. 20 mg omeprazole, 400 mg metronidazole and 250 mg clarithromycin switched over to 6 days b.d. 20 mg omeprazole and placebo antibiotics (n=27); OMC 7 consisted of 7 days b.d. omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg and 3 days b.d. omeprazole 20 mg and placebo antibiotics (n=25); OMC 10 consisted of 10 days b.d. omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (n=24). H. pylori was assessed by biopsies for culture and histology pre‐ and 4–6 weeks after OMC therapy. Metronidazole‐resistance and clarithromycin‐resistance were assessed by the E‐test.

Results:

Intention‐to‐treat‐eradication rates were: OMC 4, 96%; OMC 7, 92%; and OMC 10, 96% (N.S.). All of the three per protocol eradication rates were 100% (95% CI: 85.2–100). Of 75 isolates, 16 were metronidazole‐resistant and one was clarithromycin‐resistant.

Conclusion:

In H. pylori‐positive ulcer patients, OMC 4 is highly efficacious and as effective as OMC 7 and OMC 10. No influence of metronidazole‐resistance or clarithromycin‐resistance was observed.
Local and systemic effects of peritoneal lavage with high concentrations of adenosine in rats
Authors: Jackson E. K. , Swamy R. S. , Herzer W. A. , Mi Z.
Published: March 2003

Background:

Adenosine exerts actions which may be beneficial in treating diseases of the gastrointestinal tract. However, administered systemically, adenosine causes a ‘stress reaction’ and may adversely affect blood pressure and cardiac and renal function.

Aim:

To determine whether peritoneal lavage with adenosine provides pharmacological levels of adenosine in the intestines without elevating adenosine levels in the systemic circulation.

Methods:

Rats received an intramesenteric artery infusion of angiotensin II (30 ng/min) plus methoxamine (3 μg/min) to reduce mesenteric blood flow by approximately 60%, and adenosine solutions were instilled into the abdominal cavity. In a second study, microdialysis probes were placed in the mesenteric vein and aortic arch of rats, and the peritoneal cavity was continuously lavaged with adenosine solutions.

Results:

High concentrations (10−3 M) of adenosine normalized the mesenteric blood flow without affecting blood pressure or heart rate. High concentrations of adenosine (10−3 M) induced micromolar levels of adenosine and inosine in the mesenteric vein, without affecting adenosine or inosine levels in the aorta.

Conclusions:

Peritoneal lavage with high concentrations of adenosine provides pharmacological levels of adenosine in the gastrointestinal tract without systemic side‐effects. Peritoneal lavage with high concentrations of adenosine may be useful for the treatment of a number of diseases of the gastrointestinal tract.
Potential therapeutic applications and mechanisms of action of heparin in inflammatory bowel disease
Authors: Papa A. , Danese S. , Gasbarrini A. , Gasbarrini G.
Published: March 2003

Unfractioned heparin was recently reported to be beneficial in the treatment of inflammatory bowel disease. The available uncontrolled data show that it may be effective in steroid‐resistant ulcerative colitis with a percentage of complete clinical remission of over 70% after an average of 4–6 weeks of therapy. The administration of unfractioned heparin is not currently justified by the very limited available data.

The worsening of rectal bleeding is infrequent in treated ulcerative colitis patients and only rarely does it require blood transfusion or a colectomy. Low molecular weight heparin was used in a single trial in patients with steroid‐refractory ulcerative colitis, with results similar to those observed with unfractioned heparin.

Since a prothrombotic state has been described in inflammatory bowel disease, and microvascular intestinal occlusion seems to play a role in the pathogenesis of inflammatory bowel disease, it is reasonable that part of the beneficial effects of unfractioned heparin in inflammatory bowel disease may result from its anticoagulant properties. However, beyond its well‐known anticoagulant activity, unfractioned heparin also exhibits a broad spectrum of immunomodulating and anti‐inflammatory properties, by inhibiting the recruitment of neutrophils and reducing pro‐inflammatory cytokines. Moreover, it can restore the high‐affinity receptor binding of basic fibroblast growth factor and this would aid healing of the ulcerated mucosa.

In conclusion, unfractioned heparin may represent a safe therapeutic option for severe, steroid‐resistant ulcerative colitis, although randomized, controlled trials are needed to confirm these data.
The effect of NSAIDs and a COX‐2 specific inhibitor on Helicobacter pylori‐induced PGE2 and HGF in human gastric fibroblasts
Authors: Takahashi M. , Katayama Y. , Takada H. , Kuwayama H. , Terano A.
Published: March 2003

Background: There is compelling evidence for the pivotal role of Helicobacter pylori in the pathogenesis of gastrointestinal ulcer disease. However, despite the bacterium's toxicity, the majority of H. pylori infections are not accompanied by gastric ulcers. This implies the existence of a host mechanism offsetting H. pylori toxicity.

Aims: To evaluate gastric fibroblasts' expression of hepatocyte growth factor (HGF), which is known to facilitate gastric ulcer healing, in the presence of H. pylori; to compare the effect on H. pylori‐induced HGF expression of a COX‐2 selective inhibitor with that of nonselective nonsteroidal anti‐inflammatory drugs (NSAIDs).

Methods: Human gastric fibroblasts were cultured from human gastric mucosa obtained at surgery. Prostaglandin E2 (PGE2) and HGF were measured by EIA. The expression of COX‐2 mRNA was assessed by the TaqMan quantitative RT‐PCR system.

Results: H. pylori increased PGE2 release in gastric fibroblasts. H. pylori induced expression of COX‐2 mRNA, which indicates that PG induction by H. pylori is through COX‐2. Sulindac sulphide, etodolac and NS 398 all inhibited H. pylori‐induced PGE2 release to the same extent. These agents also inhibited H. pylori‐induced HGF release.

Conclusion: Gastric fibroblasts produce PG and HGF in response to the presence of H. pylori, which may be considered part of the human body's defensive reaction to H. pylori toxicity. This defensive mechanism is inhibited not only by COX‐2 nonselective NSAIDs but also by a COX‐2 selective inhibitor. These findings indicate the importance of COX‐2 in chronic H. pylori infection.
Induction of cyclooxygenase‐2 in mesothelial cells in peritonitis caused by perforated ulcers – an immunohistochemical study in humans
Authors: Tatsuguchi A. , Sakamoto C. , Fukuda Y. , Wada K. , Akamatsu T. , Tsukui T. , Miyake K. , Futagami S. , Kishida T. , Yamanaka N. , Kobayashi M.
Published: March 2003

Background: Increasing evidence suggests that mesothelial cells contribute to the control of inflammation in the peritoneal cavity by secreting prostaglandins. A study has shown that cyclo‐oxygenase (COX)‐2 knockout mice die partly as a result of peritonitis.

Aim: To investigate the expression and location of COX in peritonitis associated with peptic ulcer perforation.

Methods: Gastric and duodenal tissues were collected intraoperatively from nine and four patients, respectively, and immunohistochemical staining for COX‐1 and COX‐2 was performed.

Results: Histologically, all patients had severe peritonitis around the perforation sites, into which many inflammatory cells and fibroblasts had infiltrated, and reactive mesothelial cells exhibited hyperplastic change. The COX‐1 protein was not detected, whereas COX‐2 was abundant in reactive mesothelial cells near the perforation site and disappeared away from the site. Macrophages and fibroblasts around the perforation site also revealed immunostaining for COX‐2.

Conclusions: Our results showed that COX‐2 protein is induced in mesothelial cells, as well as in macrophages and fibroblasts, in inflamed peritoneal tissues associated with peptic ulcer perforation, suggesting involvement of COX‐2 in tissue repair.
Manometric and hormonal changes after distal partial gastrectomy
Authors: Yamashita Y. , Inoue H. , Ohta K. , Yoshida K. , Miyahara E. , Hirai T. , Toge T. , Adrian T. E.
Published: March 2003

Background: Alkaline oesophagitis attributable to duodenal mechanisms may induce oesophageal carcinogenesis in a rat reflux model.

Aim: To investigate the mechanism of the regurgitation after distal partial gastrectomy.

Methods: Oesophageal manometry was used in 16 patients before and after distal partial gastrectomy with reconstruction by Bilroth methods. Serum concentrations of four gastrointestinal hormones were measured by radioimmunoassay in 10 gastrectomy patients and nine healthy volunteers before and after a standardized meal.

Results: The lower oesophageal sphincter pressure was reduced to 83% after surgery. The amplitude and duration of the peristaltic waves tended to be increased, and the velocity tended to be less after surgery (amplitude 120%, duration 114%, velocity 88%). Interrupted waves appeared more frequently after surgery. The manometric changes in gastrectomized patients are considered to be disadvantageous relative to regurgitation. After surgery, gastrin and pancreatic polypeptide were completely abolished postprandially, whereas cholecystokinin and neurotensin were significantly increased.

Conclusion: The hormonal changes should have a suppressive effect on the lower oesophageal sphincter. Both the manometric and the hormonal changes may exacerbate reflux oesophagitis after distal partial gastrectomy.
Review article: hepatobiliary complications associated with total parenteral nutrition
Authors: Angelico M. , Guardia P. Della
Published: March 2003

Parenteral nutrition is often associated with hepatobiliary complications. Hepatic steatosis, intrahepatic cholestasis and biliary sludge are the most frequent. Cholestasis predominates in infants, steatosis in adults, and biliary sludge in both. Other less frequent complications are steatohepatitis and gallstones. All hepatobiliary complications are more likely to occur after extended periods of total parenteral nutrition, and are prevented by the concomitant consumption of nutrients by the enteral route. The pathogenic causes are multiple and only partially known. They include lack of gastrointestinal stimuli for biliary secretion and gall‐bladder motility, abnormalities in bile acid metabolism, the presence of sepsis, and the potentially unfavourable effects of individual components in the total parenteral nutrition formulae, including an excess of calories. Each potential mechanism and its clinical relevance is discussed in this review.
The cost of diagnosing Helicobacter pylori infection
Authors: Vakil N.
Published: March 2003

Non‐invasive testing and treatment for Helicobacter pylori has been recommended for dyspeptic patients in primary care and a number of recent studies have demonstrated the cost‐effectiveness of this approach. As the prevalence of H. pylori infection declines, the positive and negative predictive values of individual tests will change. Cost‐effectiveness is important in determining the appropriate test in individual populations. Recent studies have shown that the stool antigen test and the urea breath test have high sensitivity and specificity in the detection of H. pylori infection before and after therapy.

Cost‐effectiveness studies have shown that when the prevalence of H. pylori infection is low or intermediate, serological tests have relatively poor accuracy compared with the stool test or the urea breath test. In populations with low or intermediate prevalence (<60%) these tests should be preferred to ELISA serology or office‐based whole‐blood test or serology. This is particularly true when the prevalence of H. pylori infection is less than 30% as is seen in many developed countries. When the prevalence of H. pylori infection is high (>60%), low‐cost antibody tests are cost‐effective.
Managing the dyspeptic patient–an interactive discussion
Authors: Malfertheiner P. , Stanghellini V. , Galmiche J.‐P. , Jones R.H.
Published: March 2003

Dyspepsia, a common disorder, can present some difficult clinical dilemmas. Physicians should explore some of the more challenging cases of dyspepsia in a setting that fosters interactive dialogue among colleagues, as was the case at the interactive discussion reported below. A panel of experts presented and discussed three case histories. The audience was able to choose from among several options for diagnosis or treatment and recorded their votes by means of an electronic handset. The first case concerned the relationship between continued non‐steroidal anti‐inflammatory drug (NSAID) use and recurrent upper gastrointestinal (GI) symptoms without ulcer or Helicobacter pylori infection. The second was a woman with complex upper GI symptoms including heartburn. The last featured a young man with dyspepsia and no alarm symptoms. The first case showed that a standard dose of proton pump inhibitor (PPI) is the best treatment for patients with gastritis who continue to use NSAIDs. The second case revealed that 24‐h pH monitoring can be used to establish a relationship between symptoms and reflux episodes. The third case demonstrated that it can be difficult to make a definitive diagnosis based on clinical symptoms, and that patients with endoscopy‐negative reflux disease usually respond well to PPI therapy.
Time course of serum hepatitis C virus‐RNA during chronic hepatitis C treatment accurately predicts the type of response
Authors: Calleja J. L. , Albillos A. , Rossi I. , Moreno R. , Domper F. , MartÍnez J. L. , EscartÍn P.
Published: March 2003

Aim:

To establish the value of alanine aminotransferase normalization and hepatitis C virus‐RNA clearance as predictors of sustained virological response in naïve and relapser chronic hepatitis C patients on mono or combination therapy.

Methods:

A total of 282 hepatitis C patients were studied: 98 naïves on interferon, and 64 naïves and 75 relapsers on interferon plus oral ribavirin; 45 patients were excluded. Drugs were administered at standard doses for 12 months. Alanine aminotransferase and hepatitis C virus‐RNA were determined at baseline and at weeks 4, 12, 24, 48, and at 72 and 96 weeks after completion of therapy.

Results:

The rate of sustained response was greater (P < 0.05) in naïves and relapsers on combination therapy (33% and 48%, respectively) than in naïves on interferon alone (16%). Hepatitis C virus‐RNA significantly decreased from baseline by week 4 in naïves on interferon and relapsers on combination therapy and by week 12 in naïves on combination therapy. Alanine aminotransferase levels paralleled viremic load in naïves on interferon, yet in patients on combination therapy, alanine aminotransferase normalized independently of the virological response. During treatment, the main factor associated with sustained response was hepatitis C virus‐RNA clearance by week 4 in naïves on interferon and relapsers on combination therapy, and by week 24 in naïves on combination therapy.

Conclusion:

Clearance of viraemia constitutes the best predictor of a sustained response to therapy, but needs to be measured at patient‐specific times.
Adverse drug reactions in patients with gastroenterological diseases: does age increase the risk?
Authors: Dormann H. , Krebs S. , Muth‐Selbach U. , Criegee‐Rieck M. , Radespiel‐TrÖger M. , Levy M. , Hahn E. G. , Brune K. , Schneider H. T.
Published: March 2003

Background:

It has been claimed that the risk of adverse drug reactions increases with age. However, only limited data exist for disease‐group specific risks and none for patients with liver and gastrointestinal diseases.

Aims:

To determine the incidence and characteristics of adverse drug reactions and the physicians’ awareness of adverse drug reactions.

Methods:

During a 7‐month period, a prospective survey of 532 male patients (158 aged 65 years or older; 30%) was conducted on a hepatogastroenterological ward of a tertiary‐care university hospital, using intensive bedside and computer‐assisted drug surveillance methods.

Results:

No difference was found in the overall rate of adverse drug reactions between older and younger patients (25.9% vs. 24.2%) during 6213 treatment days. However, a significantly higher risk for developing adverse drug reactions could be shown for the elderly with biliary tract diseases (P < 0.01). Independently of age, patients suffering from gastric ulcers, acute episodes of pancreatitis, cholangitis or inflammatory bowel diseases were at high risk of adverse drug reactions. Adverse drug reaction‐associated mortality was encountered in four elderly and none of the younger patients. Secondary pharmacological effects and drug toxicity were the main types of adverse drug reactions for both age groups. Although 75.3% of the adverse drug reactions were predictable, only 37.5% of all adverse drug reactions were recognized by the staff physicians.

Conclusion:

In hepatogastroenterological patients, advancing age was not associated with an overall increased risk of adverse drug reactions except for patients with biliary tract diseases. In the elderly, adverse drug reactions were more severe and carried higher mortality. Guidelines and educational programs should be developed to increase the awareness of adverse drug reactions and their prevention, especially in high risk patients and, thus, to improve patient outcomes.