bluuebunny/crossref_metadata_2025 huggingface dataset:
Helicobacter pylori and the risk and management of associated diseases: gastritis, ulcer disease, atrophic gastritis and gastric cancer
Authors: KUIPERS E. J.
Published: October 2003

This review addresses the role of H. pylori and the effect of H. pylori eradication on gastritis, peptic ulcer disease, atrophic gastritis and gastric cancer. Specific emphasis is given to various factors that influence the clinical course of this infection. H. pylori induces chronic gastritis in virtually all infected subjects. This inflammation can lead to peptic ulceration and atrophic gastritis in a considerable number of infected subjects. A minority eventually develops gastric cancer. The risk of such complications depends upon the severity of gastritis, which is determined by various host‐ and bacteria‐related factors. Among bacterial factors, most of the evidence addresses the cagA pathogenicity island, the presence of which has been associated with more severe gastritis, peptic ulceration, atrophic gastritis and gastric cancer. Among host factors, most of the evidence focuses on acid production in response to H. pylori infection. An increase in acid secretion limits H. pylori gastritis to the antrum at the risk of duodenal ulcer disease; a reduction allows more proximal inflammation at the risk of atrophic gastritis, gastric ulcer disease, and gastric cancer. Gastritis and atrophy negatively influence acid secretion. H. pylori eradication is required in peptic ulcer disease and may be advocated in patients on profound acid suppressive therapy; it has been shown to cure gastritis and prevent ulcer recurrence. Further study is required to determine the efficacy of H. pylori eradication in the primary and secondary prevention of atrophic gastritis and gastric cancer.
Lansoprazole, clarithromycin and metronidazole for seven days in Helicobacter pylori infection
Authors: HARRIS A. W. , PRYCE D. I. , GABE S. M. , KARIM Q. N. , WALKER M. M. , LANGWORTHY H. , BARON J. H. , MISIEWICZ J. J.
Published: October 2003

Background: This study determines the efficacy and safety of a 1‐week triple therapy regimen of lansoprazole, clarithromycin and metronidazole in an area with a high prevalence of pre‐treatment metronidazole‐resistant strains of Helicobacter pylori.

Methods: Seventy‐five H. pylori positive patients with gastritis or duodenal ulcer were entered into an open study of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. H. pylori status was determined by CLOtest, histology, culture and by 13C‐urea breath test (repeated 28 days after treatment).

Results: Seventy‐one patients completed the treatment and returned for follow‐up. H. pylori was eradicated in 61 of 71 (86%) patients by per‐protocol analysis, and in 61 of 75 (81%) patients by intention‐to‐treat analysis. H. pylori was eradicated in 12 of 16 (75%) patients with metronidazole‐resistant strains compared with 22 of 24 (92%) in patients with metronidazole‐sensitive strains of H. pylori (P = 0.14). Forty‐five patients reported at least one adverse event, and three patients stopped treatment due to them (two with headaches and one with diarrhoea).

Conclusions: A 1‐week course of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. eradicates H. pylori in up to 86% of patients. It is of proven benefit in patients with pre‐treatment metronidazole‐resistant strains of H. pylori.
Sublingual nitroglycerine: effects on contractile activity of the distal oesophagus and lower oesophageal sphincter in healthy men
Authors: STACHER G. , SCHNEIDER C. , STEINRINGER H. , SATZINGER U. , WEBER U.
Published: October 2003

Background and Aims: Nitric oxide plays an important role in the control of gastrointestinal motility. This study assessed the effects of graded doses of the nitric oxide‐releasing agent, nitroglycerine, on distal oesophageal motor activity and lower oesophageal sphincter resting pressure.

Methods: Eight healthy young men received at 1‐week intervals placebo, 0.2 mg, 0.4 mg or 0.8 mg nitroglycerine sublingually under random double‐blind conditions. Sphincter pressure was recorded using a Dent sleeve and oesophageal motility using sensors 1, 4, 7 and 10 cm orad the sleeve during two 15‐min periods before and four 15‐min periods after drug administration. In minutes 4 to 6 of each period, subjects swallowed 5 mL water at 30 s intervals.

Results: After 0.2 mg and 0.4 mg nitroglycerine, amplitude, duration and area under curve of swallow‐initiated contractions were smaller than after placebo. After 0.8 mg nitroglycerine, amplitude, duration and area under curve were slightly greater than after placebo and significantly greater than after the lower nitroglycerine doses. No effects were discernible on onset latency and propagation velocity of contractions as well as on lower oesophageal sphincter resting pressure.

Conclusions: Sublingual nitroglycerine had modest, dose‐dependent effects on oesophageal peristaltic amplitude and duration, but did not affect the tone of the lower oesophageal sphincter.
Time to maximum effect of lansoprazole on gastric pH in normal male volunteers
Authors: BELL N. J. V. , HUNT R. H.
Published: October 2003

Background: The time to maximum inhibition of gastric acidity resulting from repeated oral dosing with lansoprazole 30 mg daily for 7 days was studied in nine healthy male volunteers.

Methods: Twenty‐four hour intragastric pH monitoring was performed before treatment and on days 1, 3, 5 and 7 of dosing with lansoprazole. Blood samples were taken for the estimation of plasma lansoprazole concentrations.

Results: Lansoprazole 30 mg increased mean 24‐h intragastric pH to 3.57 on day 1 compared with baseline mean pH of 2.11 (P<0.05). The mean intragastric pH during the morning period (08.00–13.00 h) was significantly higher on days 3, 5 and 7 than on day 1, but no consistent differences between day 1, 3, 5 and 7 were noted for subsequent periods (13.00–18.00, 18.00–21.00 and 23.00–07.00 h). There were no differences in mean pH between days 3, 5 and 7. Intragastric pH was maintained above pH 3 for 54.7, 60.1, 61.9 and 67.4% of the time on days 1, 3, 5 and 7, respectively.

Lansoprazole pharmacokinetic parameters did not change with daily dosing. The area under the lansoprazole plasma concentration–time curve correlated with the intragastric pH (P<0.005).

Conclusions: Lansoprazole 30 mg raised intragastric pH significantly from baseline on day 1 to a maximum effect as early as 6 h after the first dose. The degree and duration of acid suppression confirm the usefulness of lansoprazole for the treatment of acid‐related disorders.
Effect of the kappa agonist fedotozine on perception of gastric distension in healthy humans
Authors: COFFIN B. , BOUHASSIRA D. , CHOLLET R. , FRAITAG B. , DE MEYNARD C. , GENEVE J. , LEMANN M. , WILLER J.‐C. , JIAN R.
Published: October 2003

Background and Aim: Gastric hypersensitivity to mechanical distension has been observed in functional dyspepsia, but no drug is available that specifically acts on gastric afferent pathways to decrease gastric nociception. The aim of this study was to assess the effect of fedotozine, a synthetic ligand for peripheral kappa receptors, on human gastric sensitivity.

Methods: Twenty‐seven healthy volunteers were randomized to receive either fedotozine (30 mg t.d.s.) or a placebo, for 7 days. On day 7, the effects of fedotozine were tested on discomfort threshold and gastric compliance during graded isobaric and isovolumic distensions. In 16 of these subjects, the effect of this drug was tested on somatic sensitivity. In 10 other healthy volunteers the effect of fedotozine on gastric distension‐induced inhibition of the RIII reflex, a process closely related to visceral sensitivity, was also studied.

Results: During isobaric distensions, the discomfort threshold was significantly higher in subjects on fedotozine than in those on placebo (14.4±0.92 vs. 12.0±1.13 mmHg; P=0.04). Compared to placebo, fedotozine did not modify gastric compliance and somatic sensitivity. Fedotozine also reduced the inhibition of the RIII reflex induced by gastric distension.

Conclusion: Fedotozine decreases gastric sensitivity to distension by exerting specific action on gastric afferent pathways.
Lansoprazole versus ranitidine in the maintenance treatment of reflux oesophagitis
Authors: GOUGH A. L. , LONG R. G. , COOPER B. T. , FOSTER C. S. , GARRETT A. D. , LANGWORTHY C. H.
Published: October 2003

Aims: To assess the relative efficacies of lansoprazole 15 mg once daily, lansoprazole 30 mg once daily and ranitidine 300 mg b.d. in the maintenance treatment of reflux oesophagitis for 12 months.

Methods: Multicentre, out‐patient, double‐blind, parallel group, prospectively randomized clinical trial. Patients with grade 0, asymptomatic oesophagitis after 8 weeks of treatment with lansoprazole 30 mg once daily were randomized to receive lansoprazole 30 mg once daily (L30) (n=75), lansoprazole 15 mg once daily (L15) (n=86) or ranitidine 300 mg b.d. (R600) (n=74) for 12 months. Endoscopy was repeated at 6 and 12 months, and symptomatic assessment was made every 3 months. Efficacy was primarily assessed by the time to endoscopically confirmed relapse (oesophagitis grade1) and the proportion of patients who relapsed during the 12‐month study period. Severity of symptoms were secondary efficacy measures.

Results: For all patients randomized with at least one post‐baseline endoscopy (intent‐to‐treat principle) both lansoprazole 15 mg (P<0.001) and lansoprazole 30 mg (P<0.001) were significantly superior to ranitidine 600 mg with respect to time to endoscopic relapse. There was no difference between the lansoprazole groups (P=0.11). There was evidence of relapse in 27 of 86 (31.4%), 15 of 75 (20.0%) and 50 of 74 (67.6%) of the patients treated with lansoprazole 15 mg and 30 mg and ranitidine 600 mg, respectively. Patients receiving treatment with either lansoprazole dosages experienced significantly less severe heartburn and regurgitation than those patients treated with ranitidine. There were no differences between the treatment groups with respect to the severity or incidence of adverse events. No clinically significant laboratory changes were observed in any of the treatment groups. Serum gastrin levels were elevated in all treatment groups, and most markedly in those patients receiving lansoprazole, but there was no significant difference between the treatments. Morphological and immunohistochemical examination of the gastric biopsies revealed no clinically relevant changes from baseline in any of the treatment groups.

Conclusion: Both lansoprazole 15 mg and lansoprazole 30 mg once daily are significantly more effective than high‐dose ranitidine in maintaining reflux oesophagitis in remission.
One‐week triple therapy with omeprazole, amoxycillin and clarithromycin for treatment of Helicobacter pylori infection
Authors: YOUSFI M. M. , EL‐ZIMAITY H. M. T. , GENTA R. M. , GRAHAM D. Y.
Published: October 2003

Background: Multi‐drug regimens are generally required to reliably cure H. pylori infection. We previously demonstrated that a 2‐week three‐times‐a‐day regimen of amoxycillin and clarithromycin was effective against H. pylori infection.

Objectives: To evaluate the efficacy and side‐effects of a 1‐week twice‐daily dosing schedule for the treatment of H. pylori infection.

Methods: We studied the efficacy of 1‐week of therapy with 20 mg of omeprazole, 1 g of amoxycillin and 250 mg of clarithromycin, all twice daily H. pylori status was determined at entry and 4 or more weeks after completing antimicrobial therapy using histology (Genta stain) and culture.

Results: Thirty‐one patients with documented peptic ulcer disease and H. pylori infection were treated. The H. pylori infection was cured in 24 (77%, 95% CI= 58–90%) (intention‐to‐treat). In a per protocol analysis the cure rate was 23 of 29 patients (79%, 95% CI= 60–92%). One patient took only 43% of the study drugs and another withdrew following development of an anaphylactic reaction to study medication. Mild side‐effects were reported by 16% including diarrhoea, headache and altered taste. Compliance averaged 95%. Pretreatment clarithromycin resistance averaged 5% and had not been acquired by any strains post‐therapy.

Conclusion: This combination of omeprazole, amoxycillin and low‐dose clarithromycin resulted in a relatively low cure rate even in patients with clarithromycin‐sensitive isolates. Large comparative studies will be needed to define the optimal duration, dose and dosing interval if this combination of drugs is to become competitive.
Effect of short‐ and long‐term treatment with omeprazole on the absorption and serum levels of cobalamin
Authors: SCHENK B. E. , FESTEN H. P. M. , KUIPERS E. J. , KLINKENBERG‐KNOL E. C. , MEUWISSEN S. G. M.
Published: October 2003

Aims: To evaluate absorption of protein‐bound and unbound cyanocobalamin before and during treatment with omeprazole, and cobalamin levels in patients on long‐term treatment with omeprazole.

Methods: In eight former duodenal ulcer patients absorption of unbound and protein‐bound cobalamin was determined by measuring 24‐h urinary excretion of unbound 58Co‐cyanocobalamin or protein‐bound 57Co‐cyanocobalamin during a modified Schilling test. Tests were performed before and during treatment with 20 mg and 40 mg omeprazole daily for 9 days.

Serum cobalamin levels were assessed in 25 patients with gastro‐oesophageal reflux disease (GERD) before and during long‐term maintenance therapy with omeprazole. Mean treatment duration was 56 months (range 36–81 months).

Results: Urinary excretion of unbound cobalamin was unchanged with both dosages of omeprazole. Excretion of 57Co‐cyanocobalamin, however, decreased significantly during treatment with both 20 mg omeprazole (mean ±S.E.M.: 1.31±0.20 vs. 0.54±0.17%; P<0.02) and 40 mg omeprazole (1.25±0.26 vs. 0.29±0.06%; P<0.02).

Mean serum cobalamin levels (±S.E.M.) before and during therapy with omeprazole in GERD patients were 298±27 and 261±16 pg/mL (normal range 180–900 pg/mL), respectively (P=N.S.).

Conclusions: Absorption of protein‐bound, but not unbound, cyanocobalamin is decreased when measured by a modified Schilling test during treatment with omeprazole. However, no change in serum cobalamin levels was observed in patients with GERD after treatment with omeprazole for up to 7 years.
Effects of misoprostol on healing and prevention of biopsy‐induced gastroduodenal lesions occurring during the administration of diclofenac to volunteers
Authors: DORTA G. , NICOLET M. , VOUILLAMOZ D. , MARGALITH D. , BLUM A. L. , ARMSTRONG D.
Published: October 2003

Aim: To determine whether misoprostol promotes the healing of non‐steroidal anti‐inflammatory drug‐induced gastroduodenal lesions in a human experimental model.

Methods: Mucosal damage and healing of mucosal biopsy sites were assessed endoscopically in 10 healthy, Helicobacter pylori‐negative volunteers with a normal initial endoscopy: they were enrolled in a double‐blind, double‐dummy, placebo‐controlled cross‐over study. They received 2‐week courses of misoprostol (200 μg b.d.) or placebo; a water‐soluble non‐steroidal anti‐inflammatory drug diclofenac 50 mg t.d.s., was given during the second week of each dosage regimen after three endoscopic biopsies had been taken from each of the duodenum, antrum and corpus.

Results: The number of unhealed biopsy sites was not different after misoprostol or placebo, although the number of healed biopsy sites was greater in the corpus and duodenum than in the antrum. Misoprostol did not prevent the appearance of diclofenac‐induced erosions and petechiae. Epigastric discomfort was related to the intake of diclofenac and was reduced by misoprostol. Bloating and flatulence occurred more frequently with misoprostol alone and with misoprostol plus diclofenac, than with placebo alone or placebo plus diclofenac.

Conclusion: Misoprostol does not prevent new mucosal lesions induced by diclofenac in healthy volunteers and it does not accelerate the healing of the biopsy sites. Misoprostol decreases the frequency of diclofenac‐induced epigastric discomfort, but it increases gas bloating and flatulence.
Selective 5‐hydroxytryptamine antagonism: a role in irritable bowel syndrome and functional dyspepsia?
Authors: MAXTON D. G. , MORRIS J. , WHORWELL P. J.
Published: October 2003

Background: Abnormalities of gut motility and visceral pain perception are both thought to be involved in the pathogenesis of irritable bowel syndrome and may be susceptible to modulation by drugs affecting the various 5‐HT receptor subtypes. The aim of this study was to investigate the therapeutic potential of a 5‐HT3 antagonist in irritable bowel syndrome.

Methods: Fifty patients with irritable bowel syndrome were treated with ondansetron, a highly selective 5‐HT3 antagonist, in a double‐blind, placebo‐controlled cross‐over study. In addition to assessing its effect on the classical symptoms of irritable bowel syndrome (abdominal pain, distension and disordered bowel habit) its effect on symptoms often seen in irritable bowel syndrome, but more commonly associated with functional dyspepsia, was also examined.

Results: Ondansetron reduced bowel frequency (P=0.035) and improved stool consistency (P=0.002) in diarrhoea predominant irritable bowel syndrome and did not cause a deterioration of bowel habit in constipation predominant subjects. No statistically significant improvement was seen for abdominal pain or distension, although those patients who did respond were approximately twice as likely to be taking ondansetron than placebo. It was also found that ondansetron significantly improved the upper gastrointestinal symptoms of post‐prandial epigastric discomfort (P=0.008), flatulence (P=0.022) and heartburn (P=0.003).

Conclusion: The results of this study justify evaluation of the therapeutic potential of selective 5‐HT antagonists in both functional dyspepsia and irritable bowel syndrome.
the management of pouchitis
Authors: KEIGHLEY M. R. B.
Published: October 2003

Pouchitis occurs in 10–35% of patients in the first 10 years after pouch construction for ulcerative colitis. Pouchitis must be carefully defined and should not include patients with poor function or Crohn's disease. Most patients have only a single attack of pouchitis which rapidly resolves with metronidazole. Chronic pouchitis suggests some other abnormality of function which, if responsible for persistent poor function, may necessitate pouch excision.
Enhanced eradication of Helicobacter pylori by pre‐ versus post‐prandial amoxycillin suspension with omeprazole: implications for antibiotic delivery
Authors: ATHERTON J. C. , CULLEN D. J. E. , KIRK G. E. , HAWKEY C. J. , SPILLER R. C.
Published: October 2003

Background: Strategies to improve antibiotic treatment of Helicobacter pylori infection are hampered by lack of knowledge about the route of antibiotic delivery. Post‐prandial dosing with antibiotics prolongs their gastric residence time and improves their intragastric distribution, leading to improved local delivery compared with pre‐prandial dosing. We aimed to assess whether pre‐ or post‐prandial dosing with amoxycillin suspension was more effective for H. pylori eradication in an amoxycillin/omeprazole regimen.

Methods: Seventy‐nine patients with H. pylori infection were treated with omeprazole 40 mg o.m. for 28 days and amoxycillin suspension 500 mg q.d.s. for days 15–28, the amoxycillin being randomized to either 1 h before or immediately after food.

Results: The H. pylori eradication rate, for those completing the trial, was 67% (22/33) when amoxycillin suspension was given pre‐prandially, compared with 39% (15/38) when it was given post‐prandially (P<0.05). Good compliance was achieved, with H. pylori eradication in 59% (28/46) of good compliers compared with 36% (9/25) of others completing the protocol (P<0.05).

Conclusion: When given with omeprazole, pre‐prandial dosing with amoxycillin suspension is more effective for H. pylori eradication than post‐prandial dosing. This is consistent with the hypothesis that systemic rather than local delivery of amoxycillin is important for H. pylori eradication.
Long‐term follow‐up after cure of Helicobacter pylori infection with 4 days of quadruple therapy
Authors: LAI J. Y. L. , DE BOER W. A. , DRIESSEN W. M. M. , GEUSKENS L. M.
Published: October 2003

Background: We have shown that 4 days of quadruple therapy after omeprazole pre‐treatment is an effective therapy for curing H. pylori infection. In this study we investigated whether this regimen would maintain the high cure rate during long‐term follow‐up. Some recent studies have reported high recurrence rates after apparent cure. Apparently not all methods to test for cure have sufficient sensitivity to pick up small numbers of residual bacteria. This study also served to investigate whether our methods to test for cure 5–6 weeks post‐treatment were reliable.

Methods: All patients from a previous study were invited to return for a 14C‐urea breath test and serology. A representative group of 37 patients (76%) returned for a urea breath test and serology. The mean follow‐up was 14.7 months (range 11.4–23.6 months).

Results: None of the 37 patients had a positive urea breath test result. IgG antibody titres fell steadily in all patients, showing a mean decrease of 83% at the end of the follow‐up. None of the patients showed an increase in titre. Reinfection was therefore 0% (0 of 37).

Conclusion: Four days of quadruple therapy seems to be an effective therapy for the eradication of H. pylori as evidenced after long‐term follow‐up. Our biopsy methodology is reliable in identifying treatment failures 5–6 weeks post‐treatment.
Reflux symptom relief with omeprazole in patients without unequivocal oesophagitis
Authors: BATE C. M. , GRIFFIN S. M. , KEELING P. W. N. , AXON A. T. R. , DRONFIELD M. W. , CHAPMAN R. W. G. , O'DONOGHUE D. , CALAM J. , CROWE J. , MOUNTFORD R. A. , WATTS D. A. , TAYLOR M. D. , RICHARDSON P. D. I.
Published: October 2003

Background: As many as 50% of patients with reflux symptoms have no endoscopic evidence of oesophagitis. This multicentre study was designed to assess symptom relief after omeprazole 20 mg once daily in patients with symptoms typical of gastro‐oesophageal reflux disease but without endoscopic evidence of oesophagitis.

Methods: Patients (n=209) were randomized in a double‐blind study to receive either omeprazole 20 mg once daily (n=98) or placebo (n=111) for 4 weeks. Symptoms were assessed at clinic visits and using daily diary cards, with patient‐completed questionnaires providing additional data on symptoms and on psychological disturbance.

Results: On completion, symptom relief favoured omeprazole: 57% of patients on omeprazole were free of heartburn (vs. 19% on placebo), 75% were free of regurgitation (47%) and 43% were completely asymptomatic (14%), each with P<0.0001. Fewer patients in the omeprazole group required alginate/antacid relief medication (P<0.05). Symptom relief (time to first heartburn‐free day) was more rapid with omeprazole (2 vs. 5 days on placebo; P<0.01). A greater reduction in anxiety occurred in the omeprazole group (P<0.05).

Conclusion: Omeprazole 20 mg once daily is effective in providing relief of the symptoms typical of gastro‐oesophageal reflux disease in patients with essentially normal oesophageal mucosa.
Subcutaneously administered recombinant human β‐interferon in the treatment of chronic hepatitis B virus infection
Authors: GUAN R. , YEOH K. G. , YAP I. , KANG J. Y. , WEE A. , SMITH R.
Published: October 2003

Background: Treatment of chronic replicative hepatitis B virus (HBV) infection is aimed at stopping viral replication and preventing the development of chronic liver disease. β‐Interferon treatment has been less well studied than α‐interferon.

Methods: The efficacy and tolerability of a 6‐month course of subcutaneously administered human recombinant β‐interferon (rINF‐βser) was studied and the results of a low‐dose regime compared with a high‐dose regime. Twenty patients (17 men and three women), aged 24–54 years, with chronic hepatitis B virus infection (all hepatitis B surface antigen‐positive with detectable HBV‐DNA in their sera for at least 3 months prior to therapy) were randomized into two treatment groups of 10 patients each. The low‐dose group received 6×106 U/dose and the high‐dose group received 30×106 U/dose, both groups receiving their respective doses three times a week initially for 1 month and continuing for a total of 6 months.

Results: The treatment was well tolerated in both groups. None of the patients required dosage reduction or cessation of treatment because of side‐effects. HBV‐DNA decreased in all patients during treatment, demonstrating the anti‐viral efficacy of rINF‐βser, and was undetectable in 20 and 40% of patients receiving low‐dose and high‐dose regimes, respectively, at the end of 6 months treatment (P=N.S.). One year after completion of treatment, HBV‐DNA was undetectable in 50 and 30% of patients in the low‐dose and high‐dose groups, respectively (P=N.S.). However, only one patient achieved seroconversion with loss of the hepatitis B surface antigen and appearance of an anti‐hepatitis B ‘e’ antigen at the end of 18 months.

Conclusion: This study shows that subcutaneously administered rINF‐βser is well tolerated, but the optimal dose and duration of treatment still needs to be defined by further studies.
Early and late effects of low‐dose famotidine, ranitidine or placebo on pentagastrin‐stimulated gastric acid secretion in man
Authors: GRIMLEY C. E. , WEST J. M. , LOFT D. E. , COTTRELL J. , MANN S. G. , STAUFFER L. , NWOKOLO C. U.
Published: October 2003

Background: There are no published comparative studies on the effect of low‐dose H2‐antagonists on pentagastrin‐stimulated gastric acid secretion.

Methods: Twenty‐four healthy subjects were dosed with either famotidine 10 mg, ranitidine 75 mg or placebo in a balanced three‐period cross‐over design. The subjects were studied in groups of 12, simultaneously, under identical controlled environmental conditions. Gastric juice was aspirated in 15‐min aliquots during sub‐maximal (0.6 μg . h/kg) intravenous pentagastrin stimulation in the third and fourth hours (early period) and the eighth and ninth hours (late period) after oral dosing. The hydrogen ion (H+) content of gastric juice was measured ex vivo, by titrating to pH 7 known volumes of gastric aspirate against 0.1 m sodium hydroxide, using a versatile microprocessor‐controlled auto‐titration unit. Gastric acid output during the period of interest was calculated by adding the hydrogen ion content of 15‐min aliquots collected during that period. The geometric mean of the cumulative pentagastrin‐stimulated gastric acid output during the early and late periods was determined for the subjects dosed with either famotidine, ranitidine or placebo. Comparisons were performed by ANOVA.

Results: During the early period (2–4 h post‐dose), when the subjects were given placebo, mean gastric acid output was 46.6 mmol, decreasing by 76% to 11.3 mmol (P<0.001) when treated with famotidine and by 76% to 11.1 mmol (P<0.001) when treated with ranitidine. During the late period (7–9 h post‐dose), when the subjects were dosed with placebo, mean gastric acid output was 41.2 mmol, decreasing by 38% to 25.7 mmol (P<0.001) when treated with famotidine and by 27% to 30.0 mmol (P=0.007) when treated with ranitidine. The difference between the inhibitory effects of famotidine and ranitidine on gastric acid output were non‐significant during either period.

Conclusions: Low‐dose famotidine and ranitidine, intended for over‐the‐counter use, inhibit stimulated gastric acid secretion profoundly in the third and fourth hours after an oral dose. Modest effects are still detectable up to 9 h after dosing.
Effects of lansoprazole plus amoxycillin on the cure of Helicobacter pylori infection in Japanese peptic ulcer patients
Authors: KATO M. , ASAKA M. , KUDO M. , SUKEGAWA M. , KATAGIRI M. , KOSHIYAMA T. , KAGAYA H. , NISHIKAWA K. , HOKARI K. , TAKEDA H. , SUGIYAMA T.
Published: October 2003

Aim: The effect of lansoprazole plus amoxycillin on curing Helicobacter pylori infection and peptic ulcer recurrence was evaluated.

Method: The study group was composed of 68 patients with gastric ulcers and 51 with duodenal ulcers, all were H. pylori‐positive. The participants were assigned at random to the lansoprazole alone group (lansoprazole 30 mg o.m. for 6 or 8 weeks) or the lansoprazole plus amoxycillin group (lansoprazole alone regimen plus amoxycillin at 500 mg q.d.s. concomitantly for the first 2 weeks). Healed patients were not given maintenance treatment with acid secretion inhibitors. The cure rate for H. pylori infection and the ulcer recurrence rate after 1 year were investigated.

Result: The cure rate for H. pylori infection was 4.2% in patients receiving lansoprazole alone and 38.5% in patients receiving lansoprazole plus amoxycillin (P< 0.01) for gastric ulcers, and 0% in patients receiving lansoprazole alone and 61.9% in patients receiving lansoprazole plus amoxycillin (P<0.001) for duodenal ulcers. The recurrence rate was 42.3% in patients receiving lansoprazole alone and 28.6% in patients receiving lansoprazole plus amoxycillin for gastric ulcers, and 66.7% for patients receiving lansoprazole alone and 11.1% for patients receiving lansoprazole plus amoxycillin (P<0.001) for duodenal ulcers. None of the patients with gastric or duodenal ulcers cured of H. pylori infection had a recurrence.

Conclusion: Concomitant use of lansoprazole and amoxycillin increased the curative effects on H. pylori infection. However, the cure rates with this regimen remained inadequate.
Treatment of severe Crohn's disease with anti‐CD4 monoclonal antibody
Authors: CANVA‐DELCAMBRE V. , JACQUOT S. , ROBINET E. , LÉMANN M. , DROUET C. , LABALETTE M. , DESSAINT J.‐P. , ENGOUFA D. , RABIAN B, C. , MODIGLIANI R. , WIJDENES J. , REVILLARD J.‐P. , COLOMBEL J.‐F.
Published: October 2003

Background: Monoclonal CD4 antibodies have been proposed as a new immunosuppressant drug in the treatment of inflammatory bowel disease. We report our experience of treatment with a monoclonal anti‐CD4 (B‐F5) antibody in severe refractory Crohn's disease.

Methods: Twelve patients with severe refractory Crohn's disease were treated in an open clinical trial. B‐F5 was given intravenously at a dose of 0.5 mg.day/kg for 7 consecutive days (patients 1–8). For patients 9–12, B‐F5 was given at a dose of 0.5 mg.day/kg on the first day (day 0) and of 1 mg.day/kg on days 1–6. Follow‐up examinations were carried out at days 8, 15, 22 and 30. Endoscopic evaluation was performed on days 0 and 30 in eight of 12 patients.

Results: Immediately after the first infusion, one patient had dyspnoea and tachycardia requiring cessation of the treatment. Among the 11 patients who received the complete course of treatment, two had prolonged clinical improvement and two had partial clinical improvement. Significant endoscopic improvement was observed in only one patient. No sustained depletion of CD4+ cells could be observed.

Conclusion: In this uncontrolled open trial, monoclonal anti‐CD4 B‐F5 antibody was not successful in severe Crohn's disease.
Mebeverine alters small bowel motility in irritable bowel syndrome
Authors: EVANS P. R. , BAK Y.‐T. , KELLOW J. E.
Published: October 2003

Background and Aim: Despite its widespread use in irritable bowel syndrome (IBS), limited clinical data exist on the effects of mebeverine hydrochloride on gastrointestinal motility. Human motor activity in the small bowel is more reproducible than that in the large bowel; therefore the aim of this study was to determine in the small bowel the effects of oral mebeverine in both IBS patients and in healthy controls.

Methods: Twelve IBS patients (11 females/ 1 male, 46±13 years old)—predominant constipation (IBS‐C, n=6) and predominant diarrhoea (IBS‐D, n=6)—and six healthy controls, underwent continuous 48 h ambulant recording of small bowel motor activity. One low energy (400 kcal) and one high energy (800 kcal) standard meal were administered in each consecutive 24‐h period. Subjects received, in blinded fashion, placebo tablets in the first 24 h then mebeverine 135 mg q.d.s. in the second 24 h.

Results: Mebeverine had no effect on parameters of small bowel motility in controls. In contrast, in both IBS‐C (P=0.01) and IBS‐D (P<0.05) patients, phase 2 motility index was increased during mebeverine administration. Also, after mebeverine the proportion of the migrating motor complex cycle occupied by phase 2 was reduced in IBS‐D (P=0.01), while phase 2 burst frequency was reduced in IBS‐C (P<0.05). For phase 3 motor activity in IBS‐C patients, the propagation velocity was decreased (P<0.01), and the duration increased (P<0.01).

Conclusions: These findings suggest that mebeverine, in the initial dosing period, has a normalizing effect in the small bowel in IBS, enhancing contractile activity in a similar fashion to ‘prokinetic’ agents, as well as producing alterations in motor activity consistent with an ‘antispasmodic’ effect.
A randomized, placebo‐controlled trial of calcium supplementation for decreased bone density in corticosteroid‐using patients with inflammatory bowel disease: a pilot study
Authors: BERNSTEIN C. N. , SEEGER L. L. , ANTON P. A. , ARTINIAN L. , GEFFREY S. , GOODMAN W. , BELIN T. R. , SHANAHAN F.
Published: October 2003

Background: Patients with inflammatory bowel disease (IBD) have a high prevalence of osteoporosis. A number of studies have found that corticosteroid use is associated with the development of osteoporosis in these patients. Calcium supplementation may be of benefit in corticosteroid‐induced osteoporosis and calcium may be a nutrient that patients with IBD lack. Aim: To test the benefit of calcium supplementation on bone density in a pilot study over a 1‐year period, in a group of corticosteroid‐using patients with IBD, in a randomized, double‐blind, placebo‐controlled treatment study.

Methods: Corticosteroid‐using patients with IBD including males over the age of 18 years and premenopausal females, were randomized to receive either calcium carbonate 1000 mg plus vitamin D 250 IU (Oscal) or an identically matched placebo. Dual energy X‐ray absorptiometry measurements of bone density were obtained at entry and at 1 year. At entry, and every 3 months thereafter, serum was collected for the measurement of haemoglobin, biochemistry and bone hormones. Simultaneously a 24‐h urine collection was analysed for calcium excretion and creatinine clearance, and a 4‐day food record was collected to document dietary calcium and vitamin D ingestion.

Results: We found a high prevalence of moderately severe decreased bone density in corticosteroid‐using patients with IBD. The dose of prednisone in the year prior to study entry was inversely correlated with bone density at the hip (R=‐0.67, P=0.004). At study entry serum osteocalcin was inversely correlated with corticosteroid dose in the year prior to the study (R=‐0.64, P=0.02) and at study end, directly correlated with the percentage change in spine bone density (R=0.59, P=0.01). The dietary calcium intake of these patients was close to the current RDA (recommended daily intake) for premenopausal, post‐adolescent adults. Calcium supplementation with small extra doses of vitamin D conferred no obvious benefit to bone density at the end of 1 year. There was no correlation between oral calcium ingestion and bone mass measurements. Both the treatment and placebo groups' bone density remained relatively stable at 1 year, suggesting that bone loss in corticosteroid‐using patients may peak early into the use of the corticosteroids.

Conclusions: Calcium supplementation (1000 mg/day) conferred no significant benefit to bone density at 1 year in patients with corticosteroid‐using IBD patients with osteoporosis. Future investigations should explore other therapeutic avenues that may have greater effects on increasing bone density in patients who already have considerable osteoporosis.
the management of gallstone disease
Authors: HUSSAINI S. H.
Published: October 2003

Surgical techniques have an inherent advantage over oral bile therapy and extracorporeal shock‐wave lithotripsy because they remove both gallstones and the gallbladder, thus preventing stone recurrence. Moreover, surgical techniques are more effective for patients with symptomatic gallstones compared with non‐surgical techniques. Laparoscopic surgery is the best therapy from the clinical economic viewpoint being cost‐minimal, effective and beneficial compared with other surgical and medical techniques. However, non‐surgical techniques may be preferable in selected patients at high risk from general anaesthesia such as the elderly and those with significant cardio‐pulmonary disease.
Clinical economics review: the health‐care economic implications of minimal access gastrointestinal surgery
Authors: GUILLOU P. J. , WINDSOR A. J. , NEJIM A.
Published: October 2003

This article reviews some of the health‐care economic data that have been acquired in recent assessments of minimal access surgery of the digestive tract, with particular reference to laparoscopic cholecystectomy and laparoscopic surgery for gastro‐oesophageal reflux disease.
Could oral erythromycin optimize high energy continuous enteral nutrition?
Authors: LANDRY C. , VIDON N. , SOGNI P. , NEPVEUX P. , CHAUMEIL J.‐C. , COUTURIER D. , CHAUSSADE S.
Published: October 2003

Background: Intravenous erythromycin has previously been reported to stimulate gastric emptying, to inhibit gastric acid secretion and to stimulate pancreatic secretion during continuous gastric infusion of a liquid diet in healthy volunteers.

Aim: The aim of this study was to evaluate the effects of oral erythromycin (160 mg/h) on gastrointestinal function under these conditions in seven healthy subjects.

Method: This randomized double‐blind cross‐over study measured the gastric emptying rate of nutrients, gastric acid secretion, gastric pH, jejunal flow rate as well as biliopancreatic secretion and duodeno‐caecal transit time during a 19.9 kJ/min continuous infusion of a nutrient solution (4.18 kJ/mL) in the antrum over a 6‐h period by a perfusion method.

Results: The nutrition was well tolerated except by one subject with placebo perfusion. During the 6‐h period, total gastric volume and gastric volume of nutrient decreased during erythromycin administration by 22±8 and 22±6%, respectively. Gastric acid secretion was not modified by erythromycin. Lipase and bile salt outputs were significantly higher with erythromycin. The duodeno‐caecal transit time was not statistically different with drug and placebo (169±15 and 146±19 min, respectively).

Conclusion: During continuous gastric infusion of a liquid diet, the effect of oral erythromycin on gastric emptying could be useful to optimize cyclic enteral nutrition or to enhance the tolerance of enteral nutrition.
High‐dose proton pump inhibitor plus amoxycillin for the treatment or retreatment of Helicobacter pylori infection
Authors: MALATY H. , EL‐ZIMAITY H. M. T. , GENTA R. M. , COLE R. A. , GRAHAM D. Y.
Published: October 2003

Background: The combination of 120 mg of omeprazole (40 mg t.d.s.) and amoxycillin has been reported to be effective for treating H. pylori infections.

Methods: Normal volunteers with H. pylori infection received high‐dose omeprazole (40 mg t.d.s.) or lansoprazole (60 mg t.d.s.) plus amoxycillin 750 mg t.d.s. for 14 days. The studies were open label and not randomized as those receiving omeprazole plus amoxycillin had previously failed lower dose omeprazole (20 mg b.d.) plus amoxycillin therapy more than 6 months previously. Those receiving lansoprazole plus amoxycillin had not been previously treated. Four to 6 weeks after ending antimicrobial therapy, H. pylori status was determined by Genta stain of gastric mucosal biopsies.

Results: Forty‐three volunteers entered the study and 41 completed it. The overall success with high‐dose proton pump inhibitor plus amoxycillin was 34.9%. For the individual regimens the per‐protocol results were 48% (95% CI=28–69%) with lansoprazole and 12.5% (95% CI=2–38%) with omeprazole. Compliance was >95% for both regimens. Side‐effects were experienced by four lansoprazole and three omeprazole subjects, and caused two omeprazole subjects to withdraw. Cure rates were similar among different races and ethnic groups, between men and women, and between smokers and non‐smokers. The level of the pre‐treatment urea breath test also did not predict outcome.

Conclusion: High‐dose proton pump inhibitor plus amoxycillin combinations for treatment of H. pylori infection yielded unacceptable results, as the 95% confidence intervals did not include an 80% cure rate. These combinations do not yield consistent results worldwide and cannot be recommended as primary therapy.
Sucralfate and hydrocortisone enemas in the treatment of active ulcerative proctitis—a randomized single‐blind comparative study
Authors: ARDIZZONE S. , PETRILLO M. , ANTONACCI C. M. , BIANCHI PORRO G.
Published: October 2003

Background: Sucralfate is a non‐absorbable aluminium salt of sucrose octasulphate which in recent studies has proved to be of possible use in the treatment of active distal ulcerative colitis.

Aim: The aim of this randomized, single‐blind, study was to compare 10 g sucralfate with 100 mg hydrocortisone enemas in the treatment of 40 patients (26 male and 14 female; mean age 36.5 years, range 18–65 years) with active ulcerative proctitis, twice daily for 4 weeks.

Methods: A clinical, sigmoidoscopic and histological assessment was performed before and 4 weeks after the start of the therapy.

Results: Both treatments showed significant within‐treatment improvement in clinical, endoscopic and histological grades (Wilcoxon's matched pair test, P<0.05). Between‐treatment comparisons, using the Mann–Whitney test, showed that hydrocortisone is more effective than sucralfate in improving the clinical score (P<0.05).

Conclusions: Sucralfate enema treatment, which was significantly less effective than hydrocortisone enemas in this study, has very limited use in the treatment of active ulcerative proctitis.
Review article: symptom improvement through eradication of Helicobacter pylori in patients with non‐ulcer dyspepsia
Authors: LAHEIJ R. J. F. , JANSEN J. B. M. J. , VAN DE LISDONK E. H. , SEVERENS J. L. , VERBEEK A. L. M.
Published: October 2003

The aim of this article is to determine, by reviewing the literature, whether treatment of Helicobacter pylori infection in patients with non‐ulcer dyspepsia affects symptoms. Ten publications were identified through a computerized and manual literature search, and the percentage of patients with symptom improvement after successful or unsuccessful eradication therapy for H. pylori infection was calculated. In the 10 studies, symptom improvement after treatment was found in 73% of the patients that became H. pylori‐negative and 45% of the patients that remained H. pylori‐positive. Symptom improvement was modified by various clinical features and methodological aspects. If eradication of H. pylori failed, symptoms only improved over a short period. Symptom improvement was more pronounced in dyspeptic patients in whom H. pylori was eradicated than in those in whom H. pylori infection persisted.
Cure of Helicobacter pylori infection in the elderly: effects of eradication on gastritis and serological markers
Authors: PILOTTO A. , DI MARIO F. , FRANCESCHI M. , LEANDRO G. , SOFFIATI G. , SCAGNELLI M. , BOZZOLA L. , VALERIO G.
Published: October 2003

Background: Specific data on anti‐H. pylori treatments in elderly people are very scarce. The aim of the study was to evaluate in the elderly the efficacy of different anti‐H. pylori therapies and the behaviour of serum anti‐H. pylori antibodies, pepsinogen A and C, and PGA/PGC ratio induced by the anti‐H. pylori treatment.

Methods: One hundred and twenty‐one dyspeptic patients aged >60 years (mean age, 73 years; range, 61–89 years) with H. pylori‐positive gastric ulcers (17 patients), duodenal ulcers (33 patients) or chronic gastritis (71 patients) were treated with one of the following anti‐H. pylori treatments: (A) omeprazole 20 mg/day plus azithromycin 500 mg/day for 3 days; (B) omeprazole 20 mg/day plus azithromycin 500 mg/day for 3 days plus metronidazole 250 mg q.d.s. for 7 days; (C) omeprazole 40 mg/day plus azithromycin 500 mg/day for 3 days plus metronidazole 250 q.d.s. for 7 days; (D) omeprazole 20 mg/day plus clarithromycin 250 b.d. for 7 days; (E) omeprazole 20 mg/day plus clarithromycin 250 b.d. for 7 days plus metronidazole 250 q.d.s. for 7 days; and (F) omeprazole 40 mg/day plus clarithromycin 250 mg b.d. for 7 days plus metronidazole 250 mg q.d.s. for 7 days. At the baseline and 2 months after therapy, endoscopy and serum anti‐H. pylori antibodies, pepsinogen A and C, and PGA/PGC ratio were measured.

Results: Ten patients (8.2%) dropped out of the study. Six patients (4.9%) reported side‐effects. The eradication rates of the six regimens, expressed using intention‐to‐treat and per protocol analysis, were, respectively: (A) 39% and 44%; (B) 50% and 56%; (C) 65% and 77%; (D) 47% and 50%; (E) 85% and 90%; and (F) 83% and 87%. The triple therapy for regimens E and F was significantly more effective than dual therapies (regimens A and D; intention‐to‐treat=P<0.007, per protocol=P<0.001) or the triple therapy for regimens B and C (intention‐to‐treat=P<0.009, per protocol=P<0.03). Patients cured of H. pylori infection showed a significant decrease in the activity of gastritis (P<0.0001), a significant drop in IgG anti‐H. pylori (P=0.0004) and pepsinogen C (P<0.0001), and an increase in PGA/PGC ratio (P<0.001), while patients remaining H. pylori‐positive showed no changes in the serum parameters.

Conclusions: In the elderly, triple therapy with omeprazole +metronidazole+clarithromycin for 1 week is well tolerated and highly effective; anti‐H. pylori antibody and PGC serum levels decrease soon after anti‐H. pylori therapy only in patients cured of H. pylori infection.
Adverse events in patients treated with 5‐aminosalicyclic acid: 1993–1994 pharmacovigilance report for Pentasa in France
Authors: MARTEAU P. , NELET F. , LE LU M. , DEVAUX C.
Published: October 2003

Background: The incidence of the side‐effects of 5‐aminosalicylic acid (5‐ASA) in clinical practice is not known.

Aim: To present the safety reports on the use of Pentasa in France.

Methods: Pentasa‐related adverse events were recorded from 1 January 1993 to 31 December 1994. Spontaneous reports to Ferring S.A. came from physicians or pharmacovigilance regional centres.

Results: In 1993 and 1994, 51 and 79 adverse events were reported; the estimated gross incidence was 6.6 and 9.0 per million days of therapy. Detailed information was obtained in 64% of cases in 1993 and 53% in 1994. Adverse events with a high likelihood of causalty included five cases of diarrhoea, 14 cases of pancreatitis, seven cases of liver abnormalities, seven of blood dyscrasias, two cases of renal insufficiency (one of which was in a fetus), and eight of cardiac disorders including three myocarditis.

Conclusions: Pentasa seldom has adverse effects. The majority of the adverse events do not seem to be dose‐related. Clinicians should be aware of exceptional but severe adverse events including pancreatitis, cardiac disorders, blood dyscrasias and renal insufficiency.