bluuebunny/crossref_metadata_2025 huggingface dataset:
Lansoprazole in the treatment of heartburn in patients without erosive oesophagitis
Authors: Richter J. E. , Kovacs T. O. G. , Greski‐Rose P. A. , Huang B. , Fisher R.
Published: March 2003

Background

: This randomized, double‐blind, multicentre study compared lansoprazole with placebo for symptomatic relief of patients with non‐erosive gastro‐oesophageal reflux disease (GERD).

Methods

: 214 patients with symptomatic, non‐erosive GERD (moderate to severe daytime and/or night‐time heartburn greater than half the days over the past 6 months and during the 7‐ to 10‐day pre‐treatment period) were randomized to either lansoprazole 15 mg or lansoprazole 30 mg, or placebo o.d. for 8 weeks.

Results

: Daily diary data indicated that on the first treatment day a statistically significantly smaller percentage of lansoprazole patients reported daytime and night‐time heartburn and antacid usage, compared with placebo patients. Lansoprazole patients also reported statistically significant less severe daytime and night‐time heartburn on the first treatment day. During 0–4, 4–8, and 0–8 weeks of therapy, a statistically significant smaller percentage of days and nights with heartburn, less severe daytime and night‐time heartburn, and less antacid usage were observed in the lansoprazole group compared to the placebo group. The percentages of patients with adverse reactions were similar in the lansoprazole and placebo groups.

Conclusions

: The results of this study demonstrate that lansoprazole is an appropriate therapy for patients with symptomatic non‐erosive GERD.
Dilatation and constriction of rat gastric mucosal microvessels through prostaglandin EP2 and EP3 receptors
Authors: Ohno  , Katori  , Majima  , Saeki  , Boku  , Nishiyama  , Hayashi  , Saigenji
Published: March 2003

Background

: Prostaglandin (PG)E2 has both a vasodilating action and a protective function in the gastric mucosa. There are four subtypes of PGE2‐sensitive, or EP, receptors.

Aim

: To identify the subtype of EP receptors in the microvessels of the rat gastric mucosa using EP2 and EP3 receptor agonists.

Methods

: The posterior wall of the anaesthetized rat stomach was secured in a chamber and superfused with Tyrode’s solution, and the gastric microcirculation of the mucosal base was observed through a window with transillumination. PGE2 and its derivatives (20 μL) were applied topically in the window.

Results

: PGE2 (0.001–10 μmol/L), misoprostol (EP2/EP3 receptor agonist; 0.01–100 μmol/L) and butaprost (EP2 receptor agonist; 1–1000 μmol/L) dilated the arterioles dose‐dependently, but M&B 28 767 (EP3 receptor agonist; 0.001–10 μmol/L) did not alter their diameters. M&B 28 767 constricted the venules and collecting venules dose‐dependently whereas butaprost dilated them. PGE2 and misoprostol had bell‐shaped dose–response curves: constriction by low doses of PGE2 and misoprostol (0.001–0.1 μmol/L and 0.01–1 μmol/L) and dilation by high doses of PGE2 and misoprostol (0.1–100 μmol/L and 1–100 μmol/L).

Conclusions

: These results suggest that PGE2 dilated both arterioles and venules in the rat gastric mucosa through the EP2 receptors and constricted the venules through the EP3 receptors.
Review article: nonsteroidal anti‐inflammatory drug‐associated gastrointestinal complications—guidelines for prevention and treatment
Authors: Schoenfeld  , Kimmey  , Scheiman  , Bjorkman  , Laine
Published: March 2003

Chronic ingestion of NSAIDs increases the risk for gastrointestinal complications, which range from dyspepsia to gastrointestinal bleeding, obstruction, and perforation. Among patients using NSAIDs, 0.1 to 2.0% per year suffer serious gastrointestinal complications. Patients who require analgesic therapy should be carefully assessed for the lowest possible dosage and shortest duration of NSAID use and for the potential of treatment with a non‐NSAID pain reliever. These patients should also be assessed for factors that increase their risk of gastrointestinal complications, including increased age, concomitant anticoagulant or corticosteroid use, and past history of NSAID‐associated gastrointestinal complications.

The exact association between Helicobacter pylori infection and NSAID‐related ulcer disease is unclear, and the routine testing and treatment of all NSAID using patients for H. pylori infection is not recommended at this time. NSAID‐using patients who suffer from dyspepsia should have NSAIDs discontinued, the dosage changed, or be changed to a different class of NSAID. If NSAIDs cannot be discontinued, then an antisecretory agent should be initiated. Misoprostol prevents NSAID‐associated gastrointestinal complications. Proton pump inhibitors are the most effective at healing NSAID‐associated ulcers among patients who cannot discontinue NSAID therapy.
Review article: acid suppression in non‐variceal acute upper gastrointestinal bleeding
Authors: Barkun  , Cockeram  , Plourde  , Fedorak
Published: March 2003

Despite a decreased incidence of ulcer disease and improvements in the management of acute upper gastrointestinal (GI) bleeding, mortality remains at about 6–7%. Although endoscopic haemostatic therapy has been demonstrated to be the mainstay of management, the search continues for less invasive medical modalities that might also improve patient outcome.

In vitro data have indicated the important role of acid in impairing haemostasis and causing clot digestion. Therefore, theoretically, maintenance of a high intragastric pH (above 6.0) during management of upper GI bleeding is warranted. Until recently, available agents did not permit such a sustained elevation in gastric pH. Early studies with H2‐receptor antagonists have not demonstrated significant improvements in important patient outcomes, such as rebleeding, surgery or mortality.

With the availability of intravenous formulations of proton pump inhibitors, it is now possible to aim at maintaining gastric pH above 6.0 for 24 h per day. Recent clinical trial data would appear to support the use of proton pump inhibitors to decrease the rate of rebleeding and the need for surgery. This paper provides a review of non‐variceal acute GI bleeding, with special reference to the role of proton pump inhibitors in this clinical setting.
Inactivated hepatitis A vaccine in Chinese patients with chronic hepatitis B infection
Authors: Tsang  , Sung
Published: March 2003

Background

: Hepatitis B (HBV)‐infected patients have a higher morbidity and mortality when super‐infected by hepatitis A (HAV).

Aim

: To evaluate the immunogenicity and safety of a commercial inactivated HAV vaccine in Chinese patients with chronic HBV infection.

Methods

: Sixty‐five HBV‐infected patients (30 carriers, 22 chronic hepatitis, 13 cirrhosis), who were seronegative for HAV, received a dose of 1440 ELISA units of HAV vaccine at weeks 0 and 24. Twenty‐eight healthy individuals aged 18–57 years, who were seronegative for both HBV and HAV infection, also received the same vaccination regimen. Seroconversion was defined as an anti‐HAV titre ≥ 33 mIU/mL.

Results

: The seroconversion rates for the HBV‐infected patients at weeks 2, 4 and 24 were 72, 91 and 80%, respectively. The corresponding geometric mean titres (GMTs) were 103, 311 and 123 mIU/mL. In the healthy control group the seroconversion rates were 86, 93 and 89% at weeks 2, 4 and 24. The corresponding GMTs were 112, 158 and 250 mIU/mL. There was no difference in the seroconversion rates between the two groups, but healthy controls had a significantly higher GMT at week 24 (P=0.04). Side‐effects were more common in HBV patients.

Conclusion

: The HAV vaccine is equally efficacious in patients with chronic HBV infection.
Rectal and colonic mesalazine concentration in ulcerative colitis: oral vs. oral plus topical treatment
Authors: Frieri  , Pimpo  , Palumbo  , Onori  , Viscido  , Latella  , Galletti  , Pantaleoni  , Caprilli
Published: March 2003

Aim

: To measure mucosal concentrations of mesalazine in ulcerative colitis patients treated with oral mesalazine alone, compared to patients treated with both topical and oral mesalazine.

Methods

: Twenty‐two patients with mild to moderate ulcerative colitis were randomized to receive 2.4 g/day of oral mesalazine (11 patients) or 2.4 g/day oral plus 4 g/day of topical mesalazine (11 patients). After 2 weeks of treatment, endoscopic biopsies specimens were taken from the rectum and in descending colon just distal of the splenic flexure and stored to –80 °C for later assay (HPLC). Wilcoxon’s rank sum test for unpaired data was used for the statistical analysis.

Results

: Mucosal levels of mesalazine in the rectum were significantly higher in patients who received oral plus topical treatment than in those who had oral treatment alone (52.1 ng/mg, range: 13.6–122.1 vs. 0.2 ng/mg, range: 0.2–9.7, respectively; P < 0.0001). Similarly, in the descending colon, the mucosal concentrations of mesalazine were significantly higher in patients who had oral plus topical treatment than in those receiving oral treatment alone (46.6 ng/mg, range: 6–112.6 vs. 15.9 ng/mg, range: 2.3–42.4, respectively; P=0.01).

Conclusions

: Topical treatment of mesalazine significantly increases mucosal concentrations of mesalazine up to the splenic flexure, supporting the rationale to treat left‐sided ulcerative colitis with topical formulations of mesalazine.
The efficacy of octreotide therapy in chronic bleeding due to vascular abnormalities of the gastrointestinal tract
Authors: Nardone  , Rocco  , Balzano  , Budillon
Published: March 2003

Background

: The treatment of angiodysplasia and watermelon stomach, vascular abnormalities implicated in gastrointestinal bleeding of obscure origin, is a major clinical problem.

Aim

: To determine the efficacy of octreotide in patients with long‐standing gastrointestinal bleeding due to acquired angiodysplasia and watermelon stomach, resistant to previous treatments and not suitable for surgery because of old age and/or concomitant disorders.

Patients and methods

: We treated 17 patients (seven had isolated angiodysplasia, seven had multiple upper and lower gastrointestinal angiodysplasia, and three had watermelon stomach) with octreotide (0.1 mg subcutaneous t.d.s. for 6 months). Six of the patients had liver cirrhosis, one had Glanzmann‐type platelet derangement, two had cardiovascular diseases and one had chronic uraemia.

Results

: Octreotide treatment stopped bleeding in 10 patients. A transient improvement was observed in four, who needed subsequent cyclical retreatment to correct low haemoglobin levels. No effect was observed in three, probably due to the severity of the concomitant disorders.

Conclusions

: Octreotide is a safe drug that may be useful to control the recurrent gastrointestinal bleeding due to acquired angiodysplasia and watermelon stomach, especially in patients who are not candidates for surgery due to old age and/or concomitant disorders.
Standard‐dose lansoprazole is more effective than high‐dose ranitidine in achieving endoscopic healing and symptom relief in patients with moderately severe reflux oesophagitis
Authors: Jansen  , Van Oene  ,   ON BEHALF OF THE DUTCH LANSOPRAZOLE STUDY GROUP
Published: March 2003

Background:

In the treatment of reflux oesophagitis, H2‐receptor antagonists are still widely used in spite of the apparent higher efficacy of proton pump inhibitors. In an attempt to compensate for the lower efficacy, H2‐receptor antagonists are now increasingly being used at a higher dose.

Objective:

To assess whether or not standard‐dose lansoprazole (30 mg o.d.) is more effective than high‐dose ranitidine (300 mg b.d.) in moderately severe reflux oesophagitis (grades II–III).

Methods:

Lansoprazole or ranitidine was given to 133 patients for 4–8 weeks in a double‐blind, randomized, parallel group, multicentre trial.

Results:

The percentage of patients with endoscopically‐verified healing was significantly higher on lansoprazole than on ranitidine both after 4 weeks (79% vs. 42%) and 8 weeks (91% vs. 66%), though smoking had a negative impact on oesophagitis healing with lansoprazole. Heartburn, retrosternal pain and belching improved significantly better with lansoprazole than with ranitidine, as did the patient‐rated overall symptom severity. Relief of heartburn appeared somewhat faster with ranitidine, but was more pronounced with lansoprazole. The number of patients with adverse events was similar in both treatment groups.

Conclusion:

Standard‐dose lansoprazole is better than high‐dose ranitidine in moderately severe reflux oesophagitis.
Treatment of Helicobacter pylori: an overview
Authors: Axon A. T. R.
Published: March 2003

Helicobacter pylori is recognized to be a serious pathogen, but there is still controversy as to who should be treated. There is consensus for treatment of Helicobacter‐positive peptic ulcer and B‐cell lymphoma. Lymphocytic gastritis and giant‐fold gastritis (Ménétrièr's disease) may also respond to treatment. Patients with func‐tional dyspepsia have a 20% placebo response with a 5–10% ‘eradication’ response, results not dissimilar from empirical treatment with a proton pump inhibitor. A ‘test and treat’ policy for patients with uninvesti‐gated dyspepsia remains controversial. Some have suggested that eradication may increase the risk of GERD, or predispose to adenocarcinoma at the gastro‐oesophageal junction. However, PPI treatment without Helicobacter eradication induces greater inflammation in the gastric corpus, the phenotype associated with non‐cardia gastric cancer. A minority believe that Helicobacter should be eradicated in all individuals.

When choosing treatment it is logical to start with a combination of antibiotics that, in the event of failure, will allow a second combination to be used without overlap.
The continuing dilemma of dyspepsia
Authors: Stanghellini V. , Tosetti C. , Barbara G. , De Giorgio R. , Salvioli B. , Corinaldesi R.
Published: March 2003

Dyspepsia drains a substantial proportion of healthcare resources in industrialized countries and an appropriate management strategy is needed. An aetiological role for Helicobacter pylori infection has been demonstrated in a number of pathological conditions associated with dyspepsia, such as peptic ulcer and gastric malignancies, but not in functional dyspepsia. Endoscopy and diagnosis‐based treatment, H. pylori testing and eradication therapy, history taking and empirical therapy, are the main tools that are currently available for managing patients with upper gastrointestinal symptoms. Endoscopy identifies malignancies and organic diseases of the proximal gut and therefore provides reassurance to both doctors and patients. It should be recommended in older patients with suspicious symptoms and it has proven to be more cost‐effective than empirical H2‐receptor antagonists in patients with ulcer‐like symptoms. Empirical eradication in all dyspeptics without suspicious symptoms is a cost‐effective approach that cures the majority of peptic ulcers. Nevertheless, it does not control symptoms in the majority of patients, it may exacerbate gastro‐oesophageal reflux disease, and it encourages antibiotic resistance. The realities of current clinical practice require empirical therapy in most, if not all, the dyspeptics seen by general practitioners. A detailed history taking can help to diagnose gastro‐oesophageal reflux disease and to identify suspicious symptoms. Furthermore, identification of dyspepsia subgroups may provide guidance for empirical therapy. Nevertheless, even analysis of individual symptoms does not provide a sufficient diagnostic yield to differentiate functional from organic dyspepsia and appropriate investigations are needed in patients with poor response to short‐term therapy or frequent relapses.
Omeprazole or ranitidine bismuth citrate triple therapy to treat Helicobacter pylori infection: a randomized, controlled trial in Vietnamese patients with duodenal ulcer
Authors: Mao  , Lak  , Long  , Chung  , Thang  , Hop  , Chien  , Hoan  , Henley  , Perez‐Perez  , Connor  , Stone  , Chey
Published: March 2003

Aim:

To evaluate the effectiveness of triple therapy containing either omeprazole or ranitidine bismuth citrate (RBC) to treat H. pylori infection in Vietnamese duodenal ulcer patients.

Methods:

Patients infected with H. pylori were randomized to receive either omeprazole (20 mg b.d.), clarithromycin (500 mg b.d.) and amoxycillin (1 g b.d.) for 10 days (OAC), or RBC (400 mg b.d.), clarithromycin (500 mg b.d.) and amoxycillin (1 g b.d.) for 10 days (RAC). H. pylori eradication and ulcer healing was established by a follow‐up oesophagogastroduodenoscopy (EGD) at least 4 weeks after therapy. Side‐effects and compliance were assessed.

Results:

One hundred and four out of 108 (96%) patients with a duodenal ulcer were infected with H. pylori. Eighty per cent of infected patients had detectable CagA IgG antibodies. Fifty‐seven patients received OAC and 47 received RAC. OAC eradicated H. pylori in 91 and 86% of patients by per protocol (PP) and intention‐to‐treat (ITT) analysis, respectively. PP and ITT eradication rates for RAC were 96 and 91%. Ulcer healing at the follow‐up EGD was 89% with OAC and 100% with RAC. Side‐effects were minor. No patient failed to complete the protocol due to side‐effects.

Conclusion:

Triple therapy with either omeprazole or RBC is highly effective in eradicating H. pylori and healing duodenal ulcer in Vietnamese patients.
Seven‐day triple therapy with ranitidine bismuth citrate or omeprazole and two antibiotics for eradication of Helicobacter pylori in duodenal ulcer: a multicentre, randomized, single‐blind study
Authors: Spinzi  , Boni  , Bortoli  , Colombo  , Ballardini  , Venturelli  , Minoli
Published: March 2003

Aim:

To investigate the efficacy of a 1‐week triple therapy with amoxycillin, clarithromycin, and omeprazole or ranitidine bismuth citrate (RBC) in curing Helicobacter pylori infection and healing duodenal ulcers.

Methods:

One hundred and ninety‐two consecutive out‐patients with duodenal ulcer, in whom H. pylori infection was confirmed by histology and a urease biopsy test, were randomly assigned to a 1‐week treatment with either 400 mg b.d. ranitidine bismuth citrate (RAC group) or 20 mg omeprazole b.d. (OAC group) in combination with 1 g amoxycillin b.d. and 500 mg clarithromycin b.d.

Results:

Eradication of H. pylori was successful in 77% (per protocol) and 61% (intention‐to‐treat) of the patients in the RAC group and in 79% (per protocol) and 70% (intention‐to‐treat) of those in the OAC group. The difference was not significant. Per protocol analysis showed ulcers were healed in 97% of patients in the RAC group and 96% in the OAC group. Adverse effects were seen in four patients in each group: they caused discontinuation of the therapy in one patient of the OAC group.

Conclusions:

Eradication rates obtained in this study were lower than those expected on the basis of previously reported studies. The two 1‐week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.
Interferon alfa‐2b plus ribavirin for chronic hepatitis C patients who have not responded to interferon monotherapy
Authors: Lo Iacono  , Castro  , Diago  , Moreno  , Fernandez‐Bermejo  , Vega  , García  , Carbonell  , Sanz  , Borque  , García‐Buey  , García‐Monzón  , Pedreira  , Moreno‐Otero
Published: March 2003

Background:

The role of combination therapy is poorly defined in chronic hepatitis C patients who are non‐responders to interferon.

Aim:

To assess the efficacy, safety and tolerance of interferon alfa‐2b plus ribavirin in chronic hepatitis C patients who do not respond to interferon monotherapy.

Methods:

A total of 127 non‐responder patients with chronic hepatitis C received 3 mU t.i.w. of interferon alfa‐2b plus 1000–1200 mg ribavirin daily for 48 weeks. Effects of therapy were evaluated by serum aminotransferases and hepatitis C virus (HCV) RNA levels.

Results:

Twenty‐nine (23%) patients had an end‐of‐treatment response. Six months after treatment, 20 (16%) patients were sustained responders. Early loss of HCV RNA was the strongest predictor of a sustained response (P < 0.0001). Remission was also more frequent in patients with genotype 1b (P < 0.02), elevated alanine aminotransferase (P < 0.03) and low gamma glutamiltranspeptidase (P < 0.002). Treatment was discontinued in 21 (17%) patients: in 14 for intolerance and in seven due to side‐effects.

Conclusions:

Combination therapy with interferon plus ribavirin produced a sustained response in 16% of chronic hepatitis C patients who were non‐responders to interferon. This combination was safe and well tolerated.
Effect of ornidazole and clarithromycin resistance on eradication of Helicobacter pylori in peptic ulcer disease
Authors: Lehmann  , Drewe  , Terracciano  , Beglinger
Published: March 2003

Background:

Clarithromycin and nitroimidazoles such as metronidazole and ornidazole are among the most frequently used antibiotics for curing Helicobacter pylori infection. However, controversial data exist on whether their in vitro resistance has a negative impact on treatment outcome.

Methods:

Patients with H. pylori positive active peptic ulcer disease were randomly assigned to receive lansoprazole 30 mg o.d., amoxycillin 1 g b.d. and ornidazole 500 mg b.d. (LAO) or lansoprazole 30 mg o.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC) for 2 weeks. Pre‐treatment resistance to ornidazole and clarithromycin was assessed by Epsilometer (E‐) test. Four weeks after completion of treatment, patients underwent a 13C urea breath test to assess H. pylori status.

Results:

Data from 80 patients with active peptic ulcer disease and positive H. pylori status were analysed. The prevalence of primary drug resistance was 25% for metronidazole and 7.5% for clarithromycin. In patients treated with LAO, effective treatment was achieved in 87% of metronidazole‐susceptible, but only 30% of metronidazole‐resistant strains (P < 0.01). In the LAC group, therapy was successful in 81% of clarithromycin‐susceptible strains, whereas treatment failed in all patients with primary clarithromycin resistance (n = 3).

Conclusion:

Resistance against nitroimidazoles significantly affects treatment outcome in H. pylori eradication therapy.
Effect of gastric acid suppression on 13C‐urea breath test: comparison of ranitidine with omeprazole
Authors: Savarino  , Bisso  , Pivari  , Zentilin  , Bilardi  , Dulbecco  , Mele  , Tracci  , Vigneri
Published: March 2003

Background:

The assessment of the effect of H2 antagonists on the results of the urea breath test has produced controversial results.

Aim:

To assess whether standard doses of both omeprazole and H2 blockers can adversely influence the accuracy of the urea breath test.

Methods:

Sixty dyspeptic patients with ascertained Helicobacter pylori infection were recruited for this prospective, open study. They were randomized to receive either omeprazole 20 mg at 08:00 hours (n = 30) or ranitidine 300 mg at 22:00 hours (n = 30) for 14 days. The urea breath test was performed at baseline, on day 14, while patients were still taking the antisecretory drugs, and on day 21, 1 week after their cessation. Duplicate breath samples were collected after ingestion of 75 mg 13C‐urea + citric acid. A δ value > 5‰ was considered positive.

Results:

On day 14 the median δ values had declined, but not significantly (P = 0.07) compared to baseline (13.79 vs. 22.39) with omeprazole, while they had increased (P = 0.27) with ranitidine (27.21 vs. 19.46). On the same day there were five out of 30 (17%) and five out of 28 (18%) false‐negative results in the omeprazole and ranitidine groups, respectively. All these cases became positive again on day 21. However, in eight cases treated with omeprazole and 13 treated with ranitidine, there was an increase of 14‐day δ values compared to baseline.

Conclusions:

Our study shows that both omeprazole and ranitidine at standard doses are able to negatively affect the results of the urea breath test. Their adverse effect resolves within 7 days of drug cessation and therefore the withdrawal of these drugs 7 days before testing seems to be sufficient to avoid false‐negative results. The surprising finding that both antisecretory drugs reduce δ values in one group and increase them in another group of patients deserves further study.
Dyspepsia workload in urban general practice and implications of the British Society of Gastroenterology Dyspepsia Guidelines (1996)
Authors: Bodger  , Eastwood  , Manning  , Daly  , Heatley
Published: March 2003

Aim:

To define the characteristics of patients consulting with active dyspeptic symptoms in urban general practice, and to consider the implications of applying the British Society of Gastroenterology Dyspepsia management guidelines.

Design:

Prospective observational study over a period of 12 months.

Setting:

Two multipartner, two‐centre general practices in the City of Leeds (UK) with a combined target population of 11 011 registered patients.

Subjects:

A total of 340 patients consulting with active dyspeptic symptoms (52% male; mean age 53 years, range 16–89 years).

Results:

Of the practice population, 3% consulted with dyspepsia (first‐time consulter: 19%; previous consulter not yet investigated: 30%; previously investigated: 51%). Of 168 undiagnosed patients, 43% had upper abdominal pain (dysmotility‐like symptoms in 42%), 35% had reflux symptoms, 22% had mixed symptoms, 12% had ‘alarm’ symptoms and 18% had a history of NSAID use. Patients < 45 years old with simple dyspepsia accounted for 32% of undiagnosed cases. A fifth of the workload was in dealing with undiagnosed dyspeptics over 45 years old. One per cent of the population would require endoscopy if all undiagnosed cases either > 45 years or with complicated dyspepsia were investigated. Of 172 previously investigated patients, 29% had negative tests, 25% had ‘minor’ findings, and 45% had evidence of acid‐peptic disease. Patients with duodenal ulcer disease accounted for 12% of the total workload.

Conclusions:

A knowledge of the characteristics of patients consulting with dyspepsia in primary care should allow the adaptation of guidelines, to ensure advice is relevant to local case mix and compatible with local resources.
Comparative palatability of 22 liquid antacids
Authors: Temple  , Nahata
Published: March 2003

Objective:

To compare the palatability, acid neutralizing capability, and costs of different antacids.

Methods:

Volunteers between the ages of 18 and 60 years were given 22 antacids. All antacids were given during a 4‐h period in two groups of 11 antacids each. Subjects sampled each antacid in a manner similar to wine tasting and rated each antacid on its smell, taste, texture and aftertaste using a scale of 1–9; 1 being the worst and 9 the best.

Results:

A total of 73 adults completed the study. Mylanta Lemon Twist and Mylanta Cherry Crème were the most palatable antacids; however, overall the palatability of all the antacids was poor. Maalox MS Cool Mint and ES Gaviscon were the least palatable. The extra strength antacids had the most acid neutralizing capability, and thus would require smaller doses. Amphogel was the most costly antacid per mEq of acid neutralized. Age and gender did not affect the palatability scores.

Conclusion:

Although the regular strengths of Mylanta Lemon Twist and Mylanta Cherry Crème were the most palatable, the extra strength versions of these products have twice the acid neutralizing capability and thus, half the volume is required for each dose. Therefore, these agents may be the antacids of choice.
Effects of dietary fibre and olestra on regional apparent viscosity and water content of digesta residue in porcine large intestine
Authors: Mcrorie  , Brown  , Cooper  , Givaruangsawat  , Scruggs  , Boring
Published: March 2003

Background:

Increased consumption of non‐digested, non‐absorbed substrates, such as dietary fibre, can lead to an increase in colonic transit rate and stool output. The effects of dietary fibre and olestra on the consistency and water content of digesta residue within the large bowel were not known.

Aim:

The aim of this study was to determine the effects of dietary fibre and olestra on regional dehydration and apparent viscosity of digesta residue throughout the large bowel.

Methods:

Seventy‐eight pigs were fed diet alone (control) or supplemented with 40 g/day or 80 g/day dietary fibre or olestra and sacrificed 24, 48, 96 or 192 h after initiation of dosing. The large bowel was removed, divided into 13 segments, and the digesta residue/stool was analysed for apparent viscosity (peak force for extrusion) and percentage water content.

Results:

In control animals, digesta residue occurred as a continuum, from liquid in the cecum (87.9% water) to solid in the rectum (71.5% water). The relatively small decrease in percentage water content (16.4%) resulted in a marked increase in mean apparent viscosity (liquid = 87 g peak force; solid=3919 g peak force). Dietary fibre increased the percentage water content of digesta residue throughout the large bowel. In contrast, olestra decreased the percentage water content of digesta residue in the mid and distal large bowel. At 40 g/day, dietary fibre showed a significant (P < 0.05) digesta residue/stool softening effect for all time points, beginning at 24‐h (single dose). Olestra 40 g/day did not significantly soften digesta residue/stool until 48 h (2 doses, P < 0.05), and was not different from control at 96 h. At 80 g/day, both dietary fibre and olestra significantly (P < 0.01) softened digesta residue/stool at all time points. There were no liquid or oily stools at any dose or time‐point.

Conclusions:

Relatively small changes in water content result in large changes in digesta residue/stool apparent viscosity. Dietary fibre increased digesta residue/stool water content throughout the bowel, resulting in softer digesta residue/stool. In contrast, olestra decreased stool water content, yet had a similar stool softening effect compared to dietary fibre.
The impact of antibiotic resistance on the efficacy of three 7‐day regimens against Helicobacter pylori
Authors: Savarino  , Zentilin  , Pivari  , Bisso  , Mele M. Raffaella , Bilardi  , Borro  , Dulbecco  , Tessieri  , Mansi  , Borgonovo  , De Salvo  , Vigneri
Published: March 2003

Background:

Antibiotic resistance affects the success of anti‐Helicobacter pylori therapies and varies greatly from country to country.

Aim:

To compare the efficacy of three short‐term triple regimens in relation to H. pylori primary resistance in our region.

Methods:

We enrolled 210 H. pylori‐positive dyspeptic patients for this randomized, open, parallel‐group study. Three arms of 70 patients each received the following 1‐week regimens: (1) ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. + metronidazole 500 mg b.d. (RCM); (2) bismuth subcitrate 240 mg b.d. + amoxycillin 1000 mg b.d. + metronidazole 500 mg b.d. (BAM); (3) omeprazole 20 mg o.d. + clarithromycin 250 mg b.d. + metronidazole 500 mg b.d. (OCM). H. pylori was assessed by CLO‐test and histology before and 4 weeks after therapy. Antibiotic resistance was assessed by E‐test.

Results:

On intention‐to‐treat analysis RCM was more effective than OCM (84% vs. 69%; P < 0.03) and BAM (84% vs. 63%; P < 0.004). MIC determination was successful in 117 out of 210 patients (55%); metronidazole resistance was present in 52 out of 117 patients (44%) and clarithromycin resistance was present in 17 out of 117 patients (14%). Excellent cure rates were achieved when strains were sensitive to both antibiotics (100% with RCM and BAM and 90% with OCM), whereas RCM was superior to OCM (P=0.009) and BAM (P=0.001) with respect to overall resistant strains (94% vs. 57% and 38%, respectively).

Conclusions:

One‐week RCM is the best regimen to eradicate H. pylori in our geographical area. This seems to be linked to the better ability of RCM compared to OCM and BAM in overcoming the high prevalence of H. pylori resistance to both metronidazole and clarithromycin in our region.
High prevalence of Helicobacter pylori infection with dual resistance to metronidazole and clarithromycin in Hong Kong
Authors: Wang  , Wong  , Mukhopadhyay  , Berg  , Cho  , Lai  , Hu  , Fung  , Hui  , Lam
Published: March 2003

Background:

Metronidazole resistance is a common problem in most Asian countries, and clarithromycin has been widely used in Hong Kong.

Aim:

To determine the prevalence of Helicobacter pylori strains resistant to metronidazole and clarithromycin in Hong Kong and to assess the effect on eradication rates. Also to determine the genetic mutation in relation to phenotypic divergence in clarithromycin‐resistant strains.

Methods:

H. pylori were cultured from gastric biopsies obtained from 87 patients during upper endoscopy. Minimal inhibitory concentrations of metronidazole and clarithromycin were determined by Etest and agar dilution methods. Mutations in clarithromycin‐resistant strains were identified by polymerase chain reaction and restriction analysis. Random amplified polymorphic DNA fingerprinting was performed on clarithromycin‐resistant and susceptible isolates.

Results:

The prevalences of H. pylori strains resistant to metronidazole and clarithromycin were 49.4% and 10.8%, respectively, in Hong Kong. Dual resistance to metronidazole and clarithromycin were found in 7.2% of patients. The agreement between E‐test and agar dilution methods was determined by error‐rate bound analysis as 95.4% for metronidazole and 100% for clarithromycin. Dual resistant strains reduced the eradication rate to 66.7%. Among clarithromycin‐resistant strains tested, all were due to A2144G point mutation in 23S rRNA gene. Random amplified polymorphic DNA fingerprinting suggested various phenotypically mixed populations.

Conclusions:

The prevalence of metronidazole‐resistant H. pylori strains remained static whilst the prevalence of clarithromycin‐resistant strains was not rare in Hong Kong. An alarming 7.2% of patients were resistant to both the antimicrobials, which had a definite impact on treatment success. All cases of resistance to clarithromycin were due to A2144G mutation in 23S rRNA of H. pylori.
Abnormal contractile properties of rectal smooth muscle in chronic ulcerative colitis
Authors: Cook T. A. , Brading A. F. , Mortensen N. J. MCC.
Published: March 2003

Background:

Patients with ulcerative colitis have abnormal rectal motility.

Aim:

To compare the contractile properties of rectal smooth muscle from patients with ulcerative colitis and controls.

Methods:

Rectal smooth muscle strips from patients undergoing resection for ulcerative colitis or cancer (control) were mounted in an organ bath. The effects of carbachol (receptor–mediated) and potassium (causes membrane depolarization) were studied. Acetylcholinesterase histochemistry was performed and nerve counts compared.

Results:

Ulcerative colitis (n=41) and control (n=34) strips contracted in response to potassium and carbachol. Mean (S.E.M.) maximum response to potassium in the control and ulcerative colitis groups was 1.07 (0.06) g/mg and 1.02 (0.09) g/mg tissue, respectively (P=N.S.). EC50s (concentrations required to give 50% of maximal response) were 75 (1) mM and 73 (1) mM, respectively (P=N.S.). Although maximum responses to carbachol were similar, 2.12 (0.12) g/mg and 1.95 (0.12) g/mg tissue (P=N.S.), ulcerative colitis strips exhibited an increased sensitivity to carbachol, EC50s: 5.05 × 10–6  (0.55 × 10–6) M vs. 8.36 × 10–6 (0.88 × 10–6) M, P=0.002). There was no significant difference in nerve counts between the tissues, as assessed by staining for acetylcholinesterase.

Conclusions:

Ulcerative colitis tissue has an increased sensitivity to carbachol and this is not due to denervation; it may result from increased calcium release from intracellular stores since contraction due to membrane depolarization is not altered. Modulation of this pathway could potentially be used to alter rectal motility in patients with ulcerative colitis.
Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis
Authors: Green J. T. , Richardson C. , Marshall R. W. , Rhodes J. , Mckirdy H. C. , Thomas G. A. O. , Williams G. T.
Published: March 2003

Background:

Ulcerative colitis is a condition of nonsmokers in which nicotine is of therapeutic benefit.

Aims:

To examine thein vitroeffect of nicotine on colonic smooth muscle activity and the role of nitric oxide (NO) as a mediator.

Methods:

Nicotine, 1–10 μM, was administered to strips of circular muscle from the distal sigmoid colon of 9 patients with active ulcerative colitis and 18 with colorectal cancer. The effect of electrical field stimulation (EFS) was examined before nicotine was added. Finally L‐NAME, a NO synthetase inhibitor, was added before nicotine was administered again.

Results:

Muscle strips developed similar spontaneous resting tone. In response to EFS, ulcerative colitis tissue developed lower tensions than the controls. Nicotine significantly reduced the resting tone and peak tension after EFS, with a greater effect in controls. With L‐NAME, peak tensions were increased more in ulcerative colitis than controls, and nicotine produced a much smaller reduction.

Conclusions:

Nicotine reduces circular muscle activity, predominantly through the release of nitric oxide—this appears to be ‘up‐regulated’ in active ulcerative colitis. These findings may explain some of the therapeutic benefit from nicotine (and smoking) in ulcerative colitis and may account for the colonic motor dysfunction in active disease.
The effects of tegaserod (HTF 919) on oesophageal acid exposure in gastro‐oesophageal reflux disease
Authors: Kahrilas P. J. , Quigley E. M. M. , Castell D. O. , Spechler S. J.
Published: March 2003

Background:

Tegaserod (HTF 919), a 5‐HT4 receptor partial agonist, has prokinetic effects that might be useful in decreasing acid reflux in gastro‐oesophageal reflux disease (GERD).

Methods:

To investigate the potential clinical utility of tegaserod in GERD, a five‐period crossover study (balanced Latin square) was designed to evaluate the efficacy of 4 b.d. doses of tegaserod vs. placebo. Four‐hour manometry (1 h fasting and 3 h postprandial) with continuous recording of lower oesophageal sphincter pressure and distal oesophageal pH, was performed at the end of each 2‐week treatment period in 19 patients with mild‐to‐moderate GERD. Recordings were scored for mean lower oesophageal sphincter pressure, number of transient lower oesophageal sphincter relaxations, and distal oesophageal acid exposure.

Results:

Tegaserod (1 mg/day and 4 mg/day) caused a more than 50% decrease in acid exposure in the postprandial period in patients with abnormal acid exposure, although only the 1 mg/day tegaserod treatment elicited statistically significant decreasing (P < 0.05) for the entire treatment group (percentage time for which pH < 4: placebo=13%; 1 mg/day dose=5%; 4 mg/day dose=8%). A decreased number of reflux episodes was demonstrated with both the 1 mg/day and 4 mg/day tegaserod doses. There was no apparent effect on mean lower oesophageal sphincter pressure, whilst transient lower oesophageal sphincter relaxations frequency decreased in the 1–2.5 h post‐dose.

Conclusions:

Tegaserod in a dose of 1 mg/day causes a significant decrease in postprandial oesophageal acid exposure. The reduction in oesophageal acid exposure with tegaserod treatment may result from enhanced oesophageal acid clearance, improved gastric emptying, and/or reduced transient lower oesophageal sphincter relaxations.
A randomized controlled trial to assess alendronate‐associated injury of the upper gastrointestinal tract
Authors: Marshall J. K. , Rainsford K. D. , James C. , Hunt R. H.
Published: March 2003

Background:

Aminobisphosphonates are recommended for postmenopausal osteoporosis but have been associated with injury to the upper gastrointestinal tract.

Aim:

To conduct a randomized controlled trial, to assess the endoscopic damage caused by alendronate and its effect on gastric mucosal prostaglandin synthesis.

Methods:

Seventy‐six healthy volunteers age 40–60 years, with normal baseline endoscopy were randomly assigned to treatment with: (A) ASA 650 mg q.d.s.; (B) alendronate 10 mg o.d.; or (C) placebo o.d. for 14 days. Mucosal injury scores on day 14 of treatment were reported by a blinded endoscopist. Gastric biopsies were analysed for prostaglandin E2 (PGE2) concentration by radioimmunoassay.

Results:

Oesophageal injury did not differ among treatment groups. Gastric ulcers developed in five out of 26 subjects given ASA, two out of 25 given alendronate, and none of 25 given placebo. The mucosal damage scores for the alendronate group exceeded those for the placebo group in the gastric body but not at other sites. Injury scores for ASA exceeded those for placebo in the duodenum, antrum, body, and fundus. The mean change in log10[PGE2] (ng/mg protein) was − 0.07 for placebo, − 0.80 for ASA, and + 0.62 for alendronate (differences not significant).

Conclusions:

Alendronate is associated with injury and ulceration of the gastric mucosa. This effect was not associated with any significant change in gastric mucosal PGE2 levels.
Identifying responders to acid suppression in dyspepsia using a random starting day trial
Authors:   THE DANISH DYSPEPSIA STUDY GROUP:, Bytzer P. , Hansen J. M. , Rune S. , Bonnevie O. , Breinstrup H. , Funch‐Jensen P. , Matzen P. , Meineche‐Schmidt V. , Schaffalitzky De Muckadell O. B.
Published: March 2003

Background:

Functional dyspepsia is a heterogeneous condition and a uniform response to drug treatment is not likely. This may be the reason for the general failure of acid suppression in clinical trials in these patients. It may be more rewarding to identify true responders to drug treatment by a single subject trial.

Aim:

To develop and to test a novel single subject trial design (random starting day trial) in dyspeptic patients.

Patients and methods:

A total of 301 dyspeptic patients entered a 16‐day trial. All patients received placebo for the first 4 days and switched to omeprazole at a randomized and blinded day between day 5 and day 14. Response was defined as a sustained ≥ 50% decrease in symptom score occurring in relation to drug shifting.

Results:

Spontaneous response varied between 0.3% and 10.6% per day, uniformly distributed over time. Overall, 53–61% of patients with organic dyspepsia had a symptom response in relation to shifting to active treatment, compared to only 23% of patients with functional dyspepsia. The only predictor of response was symptoms suggesting gastro‐oesophageal reflux.

Conclusions:

A random starting day trial may be a valuable tool to identify response to acid suppression in dyspeptic patients.
Autonomic nervous regeneration in acetic acid‐induced ulcer from the viewpoint of synapse formation – effect of basic fibroblast growth factor and sofalcone in the rat
Authors: Nakamura M. , Kishikawa H. , Ishii H. , Kumagai N. , Tsuchimoto K.
Published: March 2003

Background: Monoclonal antibodies against GAP43 and synaptophysin, markers of regenerated nerves, have recently become available.

Aim: To investigate the regeneration of the autonomic nerves after acetic acid treatment, as well as the effect of recombinant basic fibroblast growth factor (bFGF‐CS23) and sofalcone on reinnervation.

Methods: Ulcers were induced by the direct application of 100% acetic acid to the serosal surface of the rat fundic stomach. Some rats were treated with bFGF‐CS23 or sofalcone every 12 h after the acetic acid treatment. The immunohistochemical location of GAP43 and synaptophysin was observed by confocal laser microscopy, and the uptake sites of 14C‐sofalcone were observed by autoradiography.

Results: Both GAP43 and synaptophysin immuno‐reactivities surrounding microvessels were weak in the control group, whereas in the acetic acid‐treated group, these immunoreactivities were increased. Treatment with bFGF‐CS23 and sofalcone increased these immunoreactivities. The binding sites of sofalcone coincided with the location of regenerated nerves and surface mucous cells. The progenitors of the autonomic nerves were more abundant than expected.

Conclusion: Both bFGF and sofalcone seem to stimulate nerve regeneration.
The effect of Helicobacter pylori on cell proliferation and apoptosis in gastric epithelial cell lines
Authors: Takagi A. , Watanabe S. , Igarashi M. , Koike J. , Hasumi K. , Deguchi R. , Koga Y. , Miwa T.
Published: March 2003

Background: Helicobacter pylori has been implicated in the pathogenesis of gastric cancer and malignant lymphoma. It is not known whether the bacterium stimulates cell proliferation directly or if apoptosis induced by H. pylori leads to a hyperproliferative response.

Aim: To clarify the precise mechanism of H. pylori action on gastric epithelial cell growth, we compared the response of two cell lines, Kato III (p53 deletion) and MKN 45 (p53 wild type), to the organism. To determine the role of Helicobacter vacuolating cytotoxin in gastric mucosal injury, we examined the relation between vacuolating activity and apoptosis under several conditions.

Methods: Five cytotoxic and four noncytotoxic strains of H. pylori were used, each with an inoculum of 107 cfu/mL. The effect on the growth in MKN 45 and Kato III cells was studied by MTT assay. Vacuolating cytotoxin activity was determined using RK‐13 cells.

Results: Neither cytotoxic nor noncytotoxic strains induced apoptosis, but death of MKN 45 cells was induced by pre‐treatment with interferon‐γ and culture with TNF‐α. In contrast, some strains of H. pylori increased proliferation of Kato III cells. Furthermore, cell death induced by cytotoxic strains, but not noncytotoxic strains, was significantly augmented by amoxycillin 5–50 g/mL (P = 0.0016). On the other hand, acid‐treated supernatant fluids from cultures of H. pylori showed enhanced vacuolating activity but did not induce cell death, suggesting that death is attributable to some factor other than the cytotoxin.

Conclusion: These findings suggest that H. pylori induces apoptosis by a means independent of vacuolating cytotoxin.
Long‐term use of proton pump inhibitors in GORD – help or hindrance?
Authors: Tytgat G.N.J.
Published: March 2003

Many patients with gastro‐oesophageal reflux disease (GORD) experience chronic relapses and require maintenance therapy for symptomatic relief. This article reviews possible mechanisms for chronic relapse in GORD, and discusses the risks and benefits of proton pump inhibtors as maintenance therapy for this disease. Recent medical literature was reviewed to gather information about proton pump inhibitor therapy and GORD. The reports indicated that the tendency to relapse in GORD is probably related to ongoing motor defects and to the acid rebound that follows sucessful healing therapy. Proton pump inhibitors are very effective in maintaining symptomatic and endoscopic remission in GORD. Limitations of proton pump inhibitor therapy have largely so far been clinically irrelevant. Most side‐effects are inherent consequences of any form of acid suppression therapy, and include hypergastrinaemia and rebound hyperacidity upon discontinuation of therapy. We conclude that the therapeutic balance tips toward proton pump inhibitors for treatment of GORD because their limitations are largely surpassed by excellent clinical efficacy, tolerance, and lack of serious adverse effects.