bluuebunny/crossref_metadata_2025 huggingface dataset:
Omeprazole, azithromycin and either amoxycillin or metronidazole in eradication of Helicobacter pylori in duodenal ulcer patients
Authors: Včev  , Včeva  , Štimac  , Takač  , Dmitrović  , Kovač
Published: March 2003

Background

Azithromycin is a new generation, acid stable, macrolide antibiotic that achieves remarkably high concentrations in gastric tissue (above the minimal inhibitory concentration for Helicobacter pylori) after oral administration.

Aim

To establish whether azithromycin plus omeprazole in association with either amoxycillin or metronidazole are useful in curing H. pylori infection in patients with a duodenal ulcer.

Methods

One hundred patients with active duodenal ulcers and H. pylori infection were treated with omeprazole (days 1–10, 40 mg b.d.; days 11–24, 40 mg o.m.; days 25–42, 20 mg o.m.) plus azithromycin 500 mg o.m. for the first 6 days. Patients were randomly assigned to receive either amoxycillin 1 g b.d. (OAzA group; n = 50) or metronidazole 400 mg t.d.s. (OAzM group; n = 50) during the first 10 days of treatment. H. pylori status was determined by urease test and histology before the treatment and 6 weeks after completion of therapy.

Results

Ninety‐seven patients completed the study. H. pylori infection was eradicated in 85% (41/48) of patients in the OAzA group (intention‐to‐treat analysis 82%) vs. 74% (36/49) of patients in the OAzM group (intention‐to‐treat analysis: 72%) (N.S.). All ulcers had healed after 6 weeks of omeprazole treatment. Side‐effects, usually minor, were recorded in 13% (OAzA group) and 47% (OAzM group) of patients (P < 0.001), but therapy was discontinued for only one patient in the OAzA group (N.S.).

Conclusion

Ten days of treatment with omeprazole plus (for the first 6 days) azithromycin and either amoxycillin or metronidazole provides effective regimens to cure H. pylori infection in patients with duodenal ulcer disease.
Duplex‐Doppler evaluation of the effects of propranolol and isosorbide‐5‐mononitrate on portal flow and splanchnic arterial circulation in cirrhosis
Authors: Piscaglia  , Gaiani  , Siringo  , Gramantieri  , Serra  , Bolondi
Published: March 2003

Background:

A decrease in portal flow is an important pharmacological effect of drugs used for the prophylaxis of variceal bleeding.

Aim:

To assess the acute and chronic effects of propranolol, and the effect of the acute addition of isosorbide‐5‐mononitrate, on splanchnic circulation.

Methods:

Measurements of portal blood flow volume (PBFV) and of Doppler ultrasound pulsatility index of the superior mesenteric, femoral and interlobar renal arteries were performed in 10 cirrhotic patients with varices at baseline, 90 min after propranolol or placebo, after 30 days of chronic propranolol treatment and 45 min after the addition of isosorbide‐5‐mononitrate.

Results:

The mean PBFV was significantly lower at all times than at baseline, with the greatest mean percentage decrease achieved after the addition of isosorbide‐5‐mononitrate (≥ 20% in all patients). Acute changes, however, did not predict the chronic effects in many patients. Isosorbide‐5‐mononitrate significantly increased the mesenteric and femoral pulsatility indices, whereas no significant change was observed in the kidney.

Conclusions:

Propranolol significantly decreases PBFV, but chronic effects cannot be reliably predicted by the acute change. All patients achieved a decrease in PBFV of ≥ 20% after the acute addition of isosorbide‐5‐mononitrate to chronic propranolol treatment.
Lansoprazole and secnidazole with clarithromycin, amoxycillin or pefloxacin in the eradication of Helicobacter pylori in a developing country
Authors: Ahuja  , Dhar  , Bal  , Sharma
Published: March 2003

Background:

A number of triple drug regimens using proton pump inhibitors and two antibiotics have been evaluated in the West and reported to achieve Helicobacter pylori eradication rates of over 90%. In developing countries however, these combinations have neither been well evaluated, nor the optimum treatment for H. pylori infection well defined.

Aim:

To compare the combination of a proton pump inhibitor with a nitroimidazole and another antibiotic in eradicating H. pylori infection and healing duodenal ulcer.

Methods:

Sixty consecutive patients with active duodenal ulcer who were positive for H. pylori (by rapid urease test and 14C‐urea breath test) were randomized into three treatments groups: (1) LAS (n = 21): lansoprazole 30 mg o.m., amoxycillin 500 mg q.d.s. and secnidazole 2 g on alternate days for 2 weeks; (2) LCS (n = 18): lansoprazole 30 mg o.m., clarithromycin 500 mg b.d. and secnidazole 2 g on alternate days for 1 week; (3) LPS (n = 21): lansoprazole 30 mg o.m., pefloxacin 400 mg o.m. and secnidazole 2 g on alternate days for 2 weeks. Urease and breath tests were performed at 0, 6 and 12 weeks to check for H. pylori eradication.

Results:

Intention‐to‐treat eradication rates were as follows: LAS 86%, LCS 83%, LPS 71%; the overall ulcer healing rate was 90% at 6 weeks.

Conclusions:

High H. pylori eradication rates were achieved using the amoxycillin‐ and clarithromycin‐based therapies. Fewer side‐effects, better compliance and low cost favoured the amoxycillin‐based therapy.
An ascending single‐dose safety and tolerance study of an oral formulation of rabeprazole (E3810)
Authors: Lew  , Barbuti  , Kovacs  , Sytnic  , Humphries  , Walsh
Published: March 2003

Background:

Proton pump inhibitors such as omeprazole produce a long‐lasting inhibition of gastric acid secretion associated with significant increases in plasma gastrin. Rabeprazole (E3810) is a new substituted benzimidazole H+,K+ ATPase inhibitor. It acts as an irreversible, non‐competitive inhibitor of the H+,K+ ATPase and preliminary studies demonstrate that rabeprazole produces a potent and long‐lasting inhibition of gastric acid secretion and a low level of hypergastrinaemia.

Aim:

This randomized, double‐blind, placebo‐controlled study was performed to further examine the effects of different single doses of rabeprazole on gastric acid secretion and serum gastrin.

Methods:

In this study, four groups of 10 healthy, non‐smoking Helicobacter pylori‐negative men (mean age 22.5 ± 3.9 years) received single oral doses of 10, 20, 30 and 40 mg of rabeprazole. Two of the 10 volunteers in each group received placebo as part of the double‐blind study design. All volunteers who entered into the study had a normal gastric acid secretory capacity as evaluated by pentagastrin challenge. Prior to administration of the first dose of test drug, volunteers underwent an inpatient 24‐h measurement of baseline intragastric pH. One week later, volunteers received the test drug and again underwent an inpatient 24‐h measurement of intragastric pH. During both periods, plasma samples were collected at specified intervals over 48 h and were sent for analysis of rabeprazole and gastrin levels.

Results:

Administration of rabeprazole resulted in a dose‐dependent increase in the duration and extent of intragastric pH elevation. The response among all volunteers receiving drug was significantly different from placebo, with greater acid inhibition occurring in the 30 and 40 mg groups. In addition, there was also a dose‐related increase in plasma gastrin. The pharmacokinetics of rabeprazole were similar to those of other proton pump inhibitors with a t1/2 of between 0.7 and 1.0 h. There were no clinically significant effects on patient laboratory tests or serious adverse events.

Conclusions:

The results of this study suggest that rabeprazole is as potent as omeprazole and lansoprazole in inhibiting gastric acid secretion.
The influence of cisapride on gastric tone and the perception of gastric distension
Authors: Tack  , Broeckaert  , Coulie  , Janssens
Published: March 2003

Background:

Delayed gastric emptying, impaired gastric accommodation to a meal and hypersensitivity to gastric distension have been implied in the pathophysiology of functional dyspepsia. Dyspeptic patients are often treated with the prokinetic drug cisapride.

Aim:

To assess the effects of cisapride on perception of gastric distension and gastric accommodation to a meal.

Methods:

Eighteen healthy volunteers underwent a gastric barostat study on two occasions, after pre‐treatment with placebo or cisapride 10 mg q.d.s. Graded isobaric and isovolumetric distensions were performed until the subjects reported discomfort. Volume and pressure changes were recorded and perception was scored by a questionnaire. In 10 volunteers, the amplitude of the gastric accommodation to a mixed liquid meal was also measured.

Results:

Pre‐treatment with cisapride significantly lowered thresholds for perception and for discomfort, both during isobaric (4.3 ± 0.7 vs. 3.2 ± 0.7 and 12.2 ± 1.2 vs. 9.2 ± 0.9 mmHg above minimal distending pressure (MDP), respectively, P < 0.05) and isovolumetric (256 ± 46 vs. 200 ± 35 and 644 ± 36 vs. 511 ± 40 mL, respectively, P < 0.05) distensions. Cisapride significantly enhanced the size of the meal‐induced fundus relaxation (143 ± 37 vs. 270 ± 50 mL, P < 0.05).

Conclusions:

Cisapride enhances both the perception of gastric distension and the gastric accommodation to a meal. These data suggest that cisapride may provide benefit to patients with impaired postprandial relaxation of the fundus.
Short‐term low‐dose pantoprazole‐based triple therapy for cure of Helicobacter pylori infection in duodenal ulcer patients
Authors: Pazzi  , Scagliarini  , Gamberini  , Matarese  , Rizzo  , Gullini
Published: March 2003

Background:

The eradication of Helicobacter pylori infection has been achieved using various therapy regimens, but the efficacy of the proton‐pump inhibitor pantoprazole as part of these regimens has not yet been widely tested.

Aim:

To evaluate the efficacy and tolerability of a 1‐week low‐dose pantoprazole‐based triple therapy in patients with H. pylori‐positive duodenal ulcer.

Methods:

In an open single‐centre prospective study, 71 patients with endoscopically proven active duodenal ulcer and H. pylori infection received pantoprazole 40 mg o.m. for 4 weeks, and during the first week a combination antimicrobial treatment comprising tinidazole 500 mg b.d. plus clarithomycin 250 mg b.d. H.␣pylori eradication was defined as concordant negative histology and rapid urease test performed at endoscopy 4–6 weeks after the end of treatment, confirmed 4 weeks later by 13C‐urea breath test.

Results:

Sixty‐six patients (93%) completed the trial and five patients were lost to follow‐up. H. pylori infection was cured in 61 out of the 66 patients who completed the trial (per‐protocol analysis: 92.4%, 95% CI: 83.2–97.5%; intention‐to‐treat analysis: 85.9%, 95% CI: 75.7–93.0%). At final endoscopy, 65 out of 66 patients had healed ulcer (98.5%). Mild adverse events occurred in six patients (9.1%).

Conclusions:

One‐week low‐dose pantoprazole‐based triple therapy is a simple, effective and well‐tolerated regimen for ulcer healing and H. pylori eradication in patients with duodenal ulcer.
Triple regimens using lansoprazole or ranitidine bismuth citrate for Helicobacter pylori eradication
Authors: Spadaccini  , Fanis  , Sciampa  , Russo  , Silla  , Pantaleone  , Virgilio  , Pizzicanella
Published: March 2003

Background:

A combination of an antisecretory agent with two antibiotics is considered the ‘gold standard’ for Helicobacter pylori eradication.

Objectives:

To compare the eradication rates and the safety profile of two short‐term triple therapies containing lansoprazole (L) or ranitidine bismuth citrate (RBC) as antisecretory agents.

Methods:

One hundred and twelve H. pylori‐positive patients either with peptic ulcer (56 duodenal ulcers: 25 active and 31 with a history of ulcer; 13 gastric ulcers: nine active and four with a history of ulcer) or gastritis (43) were included in an open, randomized, controlled trial. H. pylori infection was initially detected by CLO‐test and histology on antral and corpus biopsies. H.␣pylori‐positive patients were randomized to receive L plus clarithromycin (C) 250 mg b.d. plus tinidazole (T) 500 mg b.d. (LCT) or RBC plus C 250 mg b.d. and T 500 mg b.d. for 7 days (RbcCT). L or RBC were administered for a further 3 weeks in patients with active peptic ulcers. A second endoscopy was performed at least 6 weeks after the end of therapy for the assessment of H. pylori infection by CLO‐test and histology. Eradication was assumed if all the tests were negative for H. pylori.

Results:

Forty‐eight patients in the LCT group and 45 in the RbcCT group were assessed for H. pylori eradication. The eradication rates, according to intention‐to‐treat (ITT) and per protocol (PP) analyses were, respectively, 76.8% and 89.5% for the LCT group, and 73.2% and 91.1% for the RbcCT group. No statistically significant difference in eradication rates was found between the two groups by Mantel–Haenszel test. All peptic ulcers were healed. In patients in whom H. pylori had been eradicated, the severity of gastritis was significantly reduced. Side‐effects were rare. One patient in the LCT group and two in the RbcCT group were withdrawn because of adverse events.

Conclusion:

Short‐term triple therapy with either lansoprazole or RBC is equally effective and well tolerated.
The pharmacodynamics of lansoprazole administered via gastrostomy as intact, non‐encapsulated granules
Authors: Sharma  , Ugheoke  , Vasudeva  , Howden
Published: March 2003

Background:

Because of its acid‐labile nature, lansoprazole is usually administered as encapsulated enteric‐coated granules. The gelatin capsule and acid‐resistant coating of the granules have been considered essential for effective drug absorption and optimal bioavailability. Lansoprazole may attain effective plasma levels when given as non‐encapsulated intact granules, but effects on intragastric acidity are unknown.

Aim:

To test the effectiveness of non‐encapsulated, intact lansoprazole granules in suppressing intragastric acidity when administered through a gastrostomy.

Methods:

Eight men, each with an established gastrostomy, underwent baseline 24 h intragastric pH monitoring while off any acid‐suppressing medication. Via the gastrostomy, they then received 7 days of once‐daily dosing with 30 mg lansoprazole as intact granules in 3 fl. oz. of orange juice. Intragastric pH monitoring was repeated on day 7.

Results:

Mean intragastric pH pre‐dosing was 1.96 ± 0.5 (s.d.). This increased to 4.7 ± 0.6 on day 7 (P < 0.0001). Median intragastric pH rose from 1.5 to 5.2 (P < 0.0001). Before lansoprazole, the proportions of time when intragastric pH was above 3, 4 and 5 were 23.2, 13.5 and 7.5%, respectively. Corresponding values after 7 days of lansoprazole were 81.1, 70.2 and 52.3% (P < 0.0001 for each comparison).

Conclusion:

Lansoprazole can effectively suppress intragastric acidity when given through a gastrostomy as intact, non‐encapsulated granules in orange juice.
Reveiw article: factors influencing antibiotic transfer across the gastric mucosa
Authors: Goddard
Published: March 2003

The delivery of antimicrobial drugs to Helicobacter pylori within the stomach is poorly understood. The gastric environment represents a unique pharmacokinetic compartment, into which drug can be delivered directly following oral administration, or indirectly following intestinal absorption and transfer from the blood into the stomach across the gastric mucosa. Several methods have been used to study drug disposition across the gastric mucosa, including endoscopic biopsy studies, nasogastric intubation studies and animal models. Direct, or topical, delivery is limited by luminal drug degradation, drug formulation and the permeability of the mucus layer. Indirect, or systemic, delivery is limited by factors affecting the concentration gradient across the gastric mucosa and the permeability of the mucosa. These factors include intragastric pH, plasma protein binding, drug lipophilicity, the presence of active transport mechanisms, drugs that damage the gastric mucosa and inflammation secondary to H. pylori infection. Little is known about the last of these, and further research in this area should help in the rational approach to development of treatments against H. pylori.
Review article: the efficacy of infliximab in Crohn’s disease — healing of fistulae
Authors: Present D.H.
Published: March 2003

In the management of fistulae, the current therapeutic approach is the use of a combination of antibiotics and/or a combination of immunomodulatory agents. However, clinicians treating patients with fistulae, particularly those with fistulizing Crohn’s disease, have little data from controlled clinical trials of these pharmacologic agents or regimens to substantiate their use in treating this complication. Therapy with the anti‐tumour necrosis factor‐alpha antibody, infliximab, has shown promise in treating patients with Crohn’s disease and those with the disease complicated by fistulae. A recent clinical trial was designed specifically to evaluate infliximab in the treatment of fistulizing Crohn’s disease. Study results demonstrated infliximab to be the first therapeutic agent to show statistical efficacy in fistulae closure in a placebo‐controlled trial. Therapy with the chimeric monoclonal antibody was characterized by a rapid onset of closure and a lasting benefit of action. Two patient cases from the clinical trial are presented to exemplify the dramatic effectiveness of this novel therapeutic approach in modulating the immune response of patients with this debilitating complication of Crohn’s disease.
Effects of S‐0509, a novel CCKB/gastrin receptor antagonist, on acid secretion and experimental duodenal ulcers in rats
Authors: TAKEUCHI  , HIRATA  , YAMAMOTO  , KUNIKATA  , ISHIKAWA  , ISHIHARA
Published: March 2003

Background:

S‐0509, 2‐[(tert‐butoxycarbonylmethyl) [(m‐(carboxy‐phenyl)‐ureidomethyl‐carbonyl]] aminobenzo phenone, was developed as a potent and selective CCKB/gastrin receptor antagonist that does not affect the central nervous system.

Methods:

We evaluated the effects of S‐0509 on gastric acid secretion and duodenal ulcerogenic and healing responses in rats comparing it with L‐365,260, another CCKB/gastrin receptor antagonist.

Results:

S‐0509 (0.1~10 mg/kg, i.d.) was able to dose‐dependently decrease basal acid secretion and inhibit the acid secretory responses induced by both pentagastrin (60 μg/kg/h, i.v.) and peptone (10%, i.g.) but not histamine (4 mg/kg/hr, i.v.) or carbachol (60 μg/kg/h, i.v.). L‐365,260 (10 and 30 mg/kg, i.d.) caused only partial a suppression of the acid secretory response to pentagastrin but not to other stimuli, including peptone treatment. On the other hand, a duodenal ulcerogen, mepirizole (200 mg/kg, s.c.) caused an increase in acid secretion and resulted in penetrating ulcers in the proximal duodenum, and these ulcers gradually healed over 3 weeks. S‐0509 significantly inhibited both the acid secretory (> 1.0 mg/kg, i.d.) and ulcerogenic (> 3 mg/kg, p.o.) responses induced by mepirizole when it was given as a pre‐treatment. It also promoted significantly the healing of these ulcers (> 3 × 2 mg/kg, p.o.) when it was given twice daily for 14 days. In contrast, L‐365,260 (30 mg/kg) tended to reduce the severity of mepirizole‐induced duodenal ulcers, with a slight inhibition of acid secretion, but it caused no influence on the healing response of these ulcers.

Conclusion:

These results confirmed that S‐0509 is a selective CCKB/gastrin receptor antagonist with potent antisecretory action in vivo conditions, and further demonstrated that this agent not only prevents the development of duodenal ulcers but also shows healing promoting action on duodenal ulcers, probably through the blockade of CCKB/gastrin receptors.
Effects of pumaprazole (BY841), a novel reversible proton pump antagonist, and of omeprazole, on intragastric acidity before and after cure of Helicobacter pylori infection
Authors: MARTÍNEK  , BLUM  , STOLTE  , HARTMANN  , VERDÚ  , LÜHMANN  , DORTA  , WIESEL
Published: March 2003

Background:

Omeprazole produces a higher intragastric pH in the presence of Helicobacter pylori infection than after cure.

Aim:

To investigate whether this effect also occurs with pumaprazole (BY841), a reversible proton pump antagonist which, in contrast to omeprazole, does not require activation in the acid compartment of the parietal cell.

Methods:

In a randomized, crossover, double‐blind study, 24‐h intragastric pH was measured in 13 H. pylori‐positive subjects before and after a 1‐week course of omeprazole (20 mg o.d.) or of pumaprazole (100 mg b.d.). The studies were repeated after the infection was cured.

Results:

In the absence of drug administration, the median 24‐h pH values before cure (median 2.0, 90% CI: 1.2–3.2) did not differ from those after cure (median 1.5, 90% CI: 1.3–2.2; P = 0.115). The 24‐h pH values were higher before cure of the infection than after during both pumaprazole (6.0, 4.8–6.7 vs. 4.3, 2.6–5.7; P = 0.002) and omeprazole (5.8, 4.0–6.2 vs. 3.6, 2.8–5; P = 0.004). Both before and after cure, there were no significant differences between the two drugs with respect to acid inhibition over the 24‐h period. The median decrease in acid inhibition after cure of the infection (calculated as the difference in H+ activity in mmol/L) during pumaprazole (median 0.05, 90% CI: 6 × 10–4– 2.3) was no different from that during omeprazole (median 0.2, 90% CI: 3 × 10–3–1.5; P = 0.6).

Conclusions:

Both before and after cure of H. pylori infection, pumaprazole raised the intragastric pH over a 24‐h period to a similar degree as omeprazole. H. pylori infection similarly augments the pH‐increasing effect of both drugs. This effect is related to H. pylori infection and not to an increased activation of acid inhibitory agents in the parietal cell compartment.
Gastric emptying in hyperemesis gravidarum and non‐dyspeptic pregnancy
Authors: Maes  , Spitz  , Ghoos  , Hiele  , Evenepoel  , Rutgeerts
Published: March 2003

Background:

Emesis and hyperemesis are significant problems associated with early pregnancy. However, gastric emptying of solids has never been studied during early pregnancy in humans.

Aim:

To investigate gastric emptying of solids in patients recovering from hyperemesis gravidarum and in non‐dyspeptic pregnant women and to compare these results with a group of healthy non‐pregnant women.

Methods:

Fourteen patients with hyperemesis gravidarum, 10 non‐dyspeptic pregnant women and 36 non‐pregnant women in the first half of the menstrual cycle underwent a gastric emptying study. Seven non‐pregnant women repeated the test in the post‐ovulatory period.

Results:

Gastric emptying of solids was not significantly delayed in non‐dyspeptic pregnant women compared with non‐pregnant women. The emptying rate tended to be impaired in the post‐ovulatory period of the menstrual cycle. Solid emptying was significantly accelerated in patients recovering from hyperemesis gravidarum, correlating well with thyroid function in the latter group.

Conclusion:

Pregnancy in humans is not associated with decreased solid gastric emptying. In subjects recovering from hyperemesis gravidarum, solid emptying is increased, correlating well with thyroid function abnormalities. Nausea and vomiting in hyperemesis are therefore probably not due to upper gastrointestinal disorders.
Review article: the potential role of nitric oxide in chronic inflammatory bowel disorders
Authors: Perner  , Rask‐Madsen
Published: March 2003

The aetiology of the chronic inflammatory bowel diseases—ulcerative colitis and Crohn’s disease—as well as ‘microscopic colitis’—both collagenous (COC) and lymphocytic colitis (LC)—remains unknown. Autoimmune mechanisms, cytokine polymorphism, commensal bacteria, infectious agents and vascular impairment have all been proposed as playing important roles in the pathogenesis of this spectrum of diseases.

A variety of proinflammatory mediators, including tumour necrosis factor α, interleukin‐1β, interferon γ, leukotriene B4 and platelet activating factor, promote the adherence of phagocytes to the venular endothelium and extravasation of these cells into the colonic mucosa. In addition to large amounts of nitric oxide (NO), injurious peroxynitrite may be formed in the epithelium by the inducible nitric oxide synthase (iNOS), which is considered to elicit cytotoxicity by the generation of superoxide with reduced
L‐arginine availability. In active ulcerative colitis, and to a lesser extent in Crohn’s disease, a greatly increased production of NO has been demonstrated by indirect and direct measurements. Surprisingly, even higher rates of production have been observed in COC—a condition which is never associated with injurious inflammation. The latter observation favours the notion that NO promotes mucosal integrity. Further evidence for a protective role of NO in chronic inflammatory bowel disorders is provided by the observation of increased susceptibility to the induction of experi mental colitis in ‘knock‐out’ mice deficient in iNOS.

Selective inhibitors of iNOS activity, as well as topical L‐arginine, may therefore prove beneficial in inflammatory bowel disease by reducing the production of superoxide by iNOS, while only the former option may be expected to reduce diarrhoea in chronic inflammatory bowel disorders. Clearly, further experimental work needs to be done before testing topical
L‐arginine in human inflammatory bowel disease.
Eradication of Helicobacter pylori infection after ranitidine bismuth citrate, metronidazole and tetracycline for 7 or 10 days
Authors: KNIGGE  , KELLY  , PETERSON  , FENNERTY
Published: March 2003

Background

: We assessed the efficacy, tolerance, and compliance of twice‐daily triple therapy for Helicobacter pylori with ranitidine bismuth citrate, metronidazole and tetracycline for 7 or 10 days.

Methods

: 105 subjects with H. pylori infection documented by the 13C‐urea breath test were randomly assigned to a 7 or 10‐day course of ranitidine bismuth citrate 400 mg b.d., metronidazole 500 mg b.d. and tetracycline 500 mg b.d. Subjects returned at the end of therapy for assessment of side‐effects and pill count. A repeat 13C‐urea breath test was obtained 4 or more weeks after completion of therapy and cure of infection was defined as a negative test result.

Results

: Poor compliance (< 80% of medications) was seen in 2% of subjects randomized to 7 days of therapy and in 10% randomized to 10 days of therapy (P = N.S.). Intention‐to‐treat eradication rates were 56% for 7‐day and 60% for 10‐day therapy (P = N.S.). Per protocol eradication rates were 58% for 7‐day and 61% for 10‐day therapy (P = N.S.). The 10‐day intention‐to‐treat eradication rate for males was 78% and 32% for females (P < 0.01) and per protocol eradication rates were 79% and 31%, respectively (P < 0.01).

Conclusions

: Despite excellent compliance and tolerance, neither 7 nor 10 days of therapy with twice‐daily ranitidine bismuth citrate, metronidazole and tetracycline are adequate as a treatment of H. pylori infection.
The influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate triple therapy regimens for Helicobacter pylori infection
Authors: WOUDEN E. J. VAN DER , THIJS  , ZWET A. A. VAN , KOOY  , KLEIBEUKER
Published: March 2003

Aim

: To assess the influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate‐based triple therapy regimens in two consecutive studies.

Methods

: In the first study, patients with a culture‐proven Helicobacter pylori infection were treated with ranitidine bismuth citrate 400 mg, metronidazole 500 mg, and clarithromycin 500 mg, all twice daily for 1 week (RMC). In the second study, amoxycillin 1000 mg was substituted for clarithromycin (RMA). Susceptibility testing for metronidazole was performed with the E‐test. Follow‐up endoscopy was performed after ≥ 4 weeks. Antral biopsy samples were taken for histology and urease test, and culture and corpus samples for histology and culture.

Results

: 112 patients, 53 males, age 55 ± 14 years (39 duodenal ulcer, 7 gastric ulcer and 66 gastritis) were treated with RMC, and 89 patients, 52 males, age 58 ± 15 years (23 duodenal ulcer, 7 gastric ulcer and 59 gastritis) were treated with RMA. For RMC, intention‐to‐treat eradication results were 98% (59/60, 95% CI: 91–100%) and 95% (20/21, 95% CI: 76–100%) for metronidazole susceptible and resistant strains, respectively (P = 0.45). For RMA these figures were 87% (53/61, 95% CI: 76–94%) for metronidazole susceptible strains and 22% (2/9, 95% CI: 3–60%) for resistant strains (P = 0.0001).

Conclusion

: Both regimens are effective in metronidazole susceptible strains. However, in contrast to the amoxycillin‐containing regimen, that containing clarithromycin is also effective in resistant strains.
Transjugular liver biopsy in the 1990s: a 2‐year audit
Authors: PAPATHEODORIDIS  , PATCH  , WATKINSON  , TIBBALLS  , BURROUGHS
Published: March 2003

Background

: In view of the changing nature of transjugular liver biopsy, we performed an audit of the safety, adequacy and clinical impact of such biopsies in our centre over a 2‐year period from 1995 to 1997.

Methods

: One hundred and fifty‐seven transjugular biopsies were carried out in 145 patients, with prothrombin time >5 s over control and/or platelet count <50 × 109/L and/or gross ascites.

Results

: Major complications were two (1.3%) capsular perforations, which were easily plugged with coils without sequelae. Biopsy sample was adequate for histological diagnosis in 90%, inadequate in 6% and technically unsuccessful in 4% of cases. Mean biopsy size was 14.8 ± 7.7 (1–51) mm. Adequacy did not differ between cases with and without cirrhosis. Transjugular biopsy had a clinical impact (specific diagnosis or influence on patient’s management) in 50% of acute liver disease, 62% of chronic liver disease and 87% of transplant patients (P < 0.001). In chronic liver disease, it had a significantly greater clinical impact in cases trying to establish the stage rather than diagnosis (84% vs. 35%, P < 0.001).

Conclusions

: Transjugular liver biopsy is a safe procedure for high‐risk patients providing an adequate liver sample even in cirrhosis. It has a clinical impact in more than 80% of transplant patients and for staging chronic liver disease, but in only 50% (acute) or 35% (chronic) of liver disease when a diagnosis is sought.
Protection against aspirin‐induced human gastric mucosal injury by bosentan, a new endothelin‐1 receptor antagonist
Authors: DUGGAN  , STACK  , HULL  , FILIPOWICZ  , KNIFTON  , CROME  , WEBER  , BISHOP  , POLAK  , HAWKEY
Published: March 2003

Background

: Gastric ulceration induced by aspirin and by non‐steroidal anti‐inflammatory drugs (NSAIDs) is a major clinical problem. The mechanism of injury is unclear. There is evidence that NSAID‐induced injury may cause endothelin activation. Endothelin‐induced vasoconstriction has been shown to be capable of causing gastric ulceration.

Aim

: To investigate whether acute gastroduodenal injury induced in humans by aspirin can be prevented by the endothelin‐1 antagonist, bosentan.

Methods

: Eighteen healthy volunteers each received 5 × 900 mg aspirin every 12 h on three separate occasions (with either placebo, bosentan 700 mg or misoprostol 400 mg). Treatment order was randomized by Latin square design. Subjects were endoscoped and erosions counted before and 90 min after the first and last dose of aspirin. Plasma concentrations of bosentan were measured up to 5 h post‐dose.

Results

: There was a significant reduction in the mean number of erosions in the aspirin plus bosentan and aspirin plus misoprostol groups after the first dose of aspirin, compared with controls (aspirin plus placebo) (P < 0.05). This was not sustained after the fifth dose of aspirin in the aspirin plus placebo and aspirin plus bosentan groups, but was still present in the aspirin plus misoprostol group. The mean plasma concentration of bosentan measured 3.5 h post‐dose fell from 4510 (95% CI: 2791–6230) ng/mL after the 1st dose to 2508 (95% CI: 1733–3283) ng/mL after the 5th dose (P = 0.02).

Conclusion

: Endothelin receptor antagonism by bosentan can protect the gastric mucosa against aspirin damage. After five doses, bosentan levels fell, possibly because of enzyme induction, and protection was no longer evident. Further investigation is needed to assess whether higher doses would be effective.
Management of uninvestigated and functional dyspepsia: a working party report for the World Congresses of Gastroenterology 1998
Authors: Talley  , Axon  , Bytzer  , Holtmann  , Lam  , Zanten S. Velohuyzen Van
Published: March 2003

Background

: The management of dyspepsia is controversial.

Methods

: An international Working Party was convened in 1998 to review management strategies for dyspepsia and functional dyspepsia, based on a review of the literature and best clinical practice.

Results

: Dyspepsia, defined as pain or discomfort centred in the upper abdomen, can be managed with reassurance and over‐the‐counter therapy if its duration is less than 4 weeks on initial presentation. For patients with chronic symptoms, clinical evaluation depends on alarm features including patient age. The age cut off selected should depend on the age specific incidence when gastric cancer begins to increase, but in Western nations 50 years is generally an acceptable age threshold. In younger patients without alarm features, Helicobacter pylori test and treatment is the approach recommended because of its value in eliminating the peptic ulcer disease diathesis. If, after eradication of H. pylori, symptoms either are not relieved or rapidly recur, then an empirical trial of therapy is recommended. Similarly, in H. pylori‐negative patients without alarm features, an empirical trial (with antisecretory or prokinetic therapy depending on the predominant symptom) for up to 8 weeks is recommended. If drugs fail, endoscopy should be considered because of its reassurance value although the yield will be low. In older patients or those with alarm features, prompt endoscopy is recommended. If endoscopy is non‐diagnostic, gastric biopsies are recommended to document H. pylori status unless already known. While treatment of H. pylori is unlikely to relieve the symptoms of functional dyspepsia, the long‐term benefits probably outweigh the risks and treatment can be considered on a case‐by‐case basis. In H. pylori‐negative patients with documented functional dyspepsia, antisecretory or prokinetic therapy, depending on the predominant symptom, is reasonable, assuming reassurance and explanation are insufficient, unless patients have already failed this approach. Other treatment options include antidepressants, antispasmodics, visceral analgesics such as serotonin type 3 receptor antagonists, and behavioural or psychotherapy although these are all of uncertain efficacy. Long‐term drug treatment in functional dyspepsia should be avoided; intermittent short courses of treatment as needed is preferred.

Conclusion

: The management of dyspepsia recommended is based on current best evidence but must be tailored to local factors such as practice setting, the background prevalence of H. pylori and structural disease, and costs.
Review article: malnutrition and maltreatment—a comment on orlistat for the treatment of obesity
Authors: Cahill  , Lean
Published: March 2003

The prevalence of obesity has doubled in the last 10 years and is now reaching epidemic proportions. There is a significant comorbidity and financial cost associated with this disorder. Orlistat is an intestinal lipase inhibitor that is approved for the treatment of obesity.

Recent randomized, double‐blind, placebo‐controlled trials have demonstrated the benefit of orlistat used in conjunction with a hypocaloric (low‐fat) diet in facilitating weight reduction and the long‐term maintenance of this weight loss. Patients treated with orlistat lost a greater amount of initial body weight compared to those who received placebo. After 24 months of treatment, weight loss of more than 5% was maintained in a greater number of those treated with orlistat. This was associated with significant reductions in cardiovascular risk factors (cholesterol, LDL cholesterol, LDL:HDL cholesterol ratio). The main adverse events are related to fat malabsorption, with potential losses of fat‐soluble vitamins and other compounds.

Orlistat as a treatment for obesity, when prescribed within present guidelines, can aid modest weight loss in about one‐third of patients. More importantly, it can assist in the maintenance of weight loss with major medical benefits for these patients.
Helicobacter pylori infection is a protective factor for bleeding gastric ulcers but not for bleeding duodenal ulcers in NSAID users
Authors: Santolaria  , Lanas  , Benito  , Pérez‐Aisa  , Montoro  , Sainz
Published: March 2003

Background

: The effect of Helicobacter pylori infection on NSAID‐induced gastroduodenal damage is unclear.

Aim

To determine the role of H. pylori and NSAID use in complicated peptic ulcers.

Methods

: A total of 185 consecutive patients with bleeding peptic ulcers and 185 hospitalized matched controls were studied prospectively. Additionally, 75 consecutive uncomplicated peptic ulcers and 75 community controls were also studied. Active H. pylori infection was determined by urea breath test and/or both urease test and histology. Serum CagA and VacA status were determined at random in 135 infected patients and 82 controls. NSAID use was determined by structured data collection.

Results

: H. pylori (odds ratio [OR]=5.98; 2.9–12.3) and NSAID use (OR=5.74; 3.4–9.7) were independent risk factors for duodenal ulcer bleeding, whereas NSAID use was the main risk factor for bleeding gastric ulcers (OR=12.4; 5.5–27.9). Interaction of both factors was associated with reduced risk for bleeding gastric ulcers (OR=0.19; 0.04–0.88) but not for bleeding duodenal ulcers, which showed a similar risk to any one factor alone. This was observed for all types of NSAID use, including low‐dose aspirin, and infection by CagA positive strains. H. pylori was the only factor involved in common uncomplicated duodenal ulcers.

Conclusion

: Interaction of both H. pylori infection and NSAID use decreases the risk of bleeding due to gastric ulcers, but not that due to duodenal ulcers.
Randomised double‐blind comparison of simethicone with cisapride in functional dyspepsia
Authors: Holtmann  , Gschossmann  , Karaus  , Fischer  , Becker  , Mayr  , Gerken
Published: March 2003

Aim

: To compare the efficacy of simethicone with cisapride in patients with functional (non‐ulcer) dyspepsia.

Methods

: After standardized diagnostic work‐up and at least 6‐days wash‐out of medication, 177 patients with functional dyspepsia were enrolled; 173 of them (age 19–71 years) were randomized and treated using a double‐dummy technique with simethicone (84 mg t.d.s.) or cisapride (10 mg t.d.s.). At baseline and after 2 and 4 weeks, the intensity of the symptoms was scored from 0 (absent) to 3 (severe) using a standardized symptom questionnaire. Efficacy of the treatment was judged by the patients as ‘very good’, ‘good’, ‘moderate’ or ‘no effect’.

Results

: A total of 166 patients completed the trial. After 2 and 4 weeks, 34% and 46% (respectively), of the patients treated with simethicone judged the improvement in symptoms to be excellent compared to 13% and 22% (respectively) of patients treated with cisapride (P < 0.01). After 2 weeks the difference in the improvement in the global symptom score was significantly better (Δ30.7%, P < 0.001) for simethicone than for cisapride, while this difference failed statistical significance after 4 weeks (Δ10.2%, P=0.11).

Conclusions

: In patients with functional dyspepsia, simethicone relieves symptoms during the first 2 weeks of treatment significantly better than cisapride.
Non‐steroidal anti‐inflammatory drugs and Helicobacter pylori
Authors: Barr M. , Buckley M. , O'morain C.
Published: March 2003

Non‐steroidal anti‐inflammatory drugs (NSAIDs) and Helicobacter pylori are well‐recognized causes of gastroduodenal mucosal damage. This damage is mediated through the effects of both agents on acid secretion, neutrophil activity and function, and prosta‐ glandin metabolism. Clinical trials on the interrelation‐ ship between H. pylori, NSAIDs and gastroduodenal mucosal injury have yielded conflicting results. No consensus has been reached on what recommenda‐ tions should be implemented with regard to H. pylori eradication in patients on long‐term NSAID therapy. At present, the presence of H. pylori is identified at endoscopy and eradication is carried out in symptomatic patients. Asymptomatic patients remain a dilemma that requires further investigation. Clinical practice will continue to be tailored to a patient's individual requirements. Therefore, in patients at risk of gastrointestinal haemorrhage, and on NSAID therapy, acid suppression therapy should be prescribed.
The efficacy of a 40‐mg extended‐release formulation of cisapride in the treatment of patients with gastro‐oesophageal reflux
Authors: Katschinski  , Schirra  , Arnold
Published: March 2003

Background:

This study was conducted to assess the efficacy of a novel 40‐mg extended‐release formulation of cisapride in reducing gastro‐oesophageal reflux.

Methods:

According to a double‐blind, randomized, placebo‐controlled design, 19 patients with pathological gastro‐oesophageal reflux were treated with extended (40 mg o.d.) or immediate (10 mg q.d.s.) release formulations for two periods of 4 days each (pH‐monitoring on day four). Patients received identical treatments in both periods to allow limits of agreement defining equivalent potency of both formulations to be derived from intra‐individual variability of treatment effects.

Results:

The extended‐release formulation decreased total and upright reflux times by 5.5 ± 1.3% and 8.1 ± 2.1% (P < 0.001), respectively. It did not change the percentage supine reflux time but diminished the mean duration of reflux episodes by 1.0 ± 0.4 min (P=0.005). The total number of reflux episodes remained unaltered with both formulations. Immediately‐released cisapride decreased total, upright, and supine acid exposures by 5.8 ± 1.3%, 6.8 ± 1.6% (P < 0.002) and 3.6 ± 1.8%, respectively, and mean duration of episodes by 0.9 ± 0.2 min (P ≤ 0.05). Equivalent potency for both formulations was accepted in terms of percentage total and upright acid exposure and mean duration of episodes.

Conclusions:

The 40‐mg extended‐release formulation of cisapride decreases total acid exposure and in this study is equivalent to the conventional immediate‐release 10 mg q.d.s. regimen. Cisapride primarily interferes with reflux by improving oesophageal acid clearance.
Lack of a pharmacokinetic interaction between lansoprazole or pantoprazole and theophylline
Authors: Pan  , Goldwater  , Zhang  , Pilmer  , Hunt
Published: March 2003

Aim:

To study the potential pharmacokinetic interaction between lansoprazole or pantoprazole and theophylline at steady state.

Methods:

Theophylline 200 mg extended‐release formulation was administered twice daily on days 1–11 to 30 healthy, non‐smoking males. On days 5–11, 15 subjects received concomitant lansoprazole 30 mg once daily (o.d.) and 15 subjects received concomitant pantoprazole 40 mg o.d.

Results:

No significant changes in the steady‐state theophylline maximum plasma concentration (Cmax), time to Cmax (Tmax), minimum plasma concentration (Cmin), area under the plasma concentration–time curve over the 12‐h dosing interval (AUC0–12), or apparent total oral clearance (CL/F) were observed within the two treatment groups when theophylline was administered alone or in combination with lansoprazole or pantoprazole. In addition, no significant differences in the changes of steady‐state theophylline pharmacokinetics from day 4 to day 11 were noted between the two treatment groups. Treatment with theophylline in combination with either lansoprazole or pantoprazole was well tolerated. All adverse events were transient and rated mild to moderate in severity.

Conclusion:

Co‐administration of either lansoprazole or pantoprazole in healthy subjects does not significantly affect the steady‐state pharmacokinetics of theophylline at the therapeutic doses tested.
An evaluation of whole blood testing for Helicobacter pylori infection in the Chinese population
Authors: Wong  , Wong  , Tang  , Lai  , Yuen  , Hu  , Chan  , Lau  , Lai  , Lam
Published: March 2003

Background:

Near patient tests for Helicobacter pylori were developed to assist in the management of dyspepsia patients in general practice. Most studies were performed in western populations.

Aim:

To evaluate the rapid whole blood test (Flexpack HP) for H. pylori in the Chinese population.

Methods:

Consecutive dyspeptic patients referred for upper endoscopy were recruited. During upper endoscopy, biopsies were taken from the antrum and corpus for rapid urease test (CLO test) and histological examination. After endoscopy, the whole blood test (FlexPack HP) was performed according to the manufacturer’s instruction. Patients then received a 13C‐urea breath test. Results of the whole blood test were compared with the gold standard (CLO test, histology and 13C‐urea breath test).

Results:

A total of 294 consecutive patients gave a valid Flexpack HP result for interpretation. The mean age of patients was 47.7 (range 15–85) years. Analysis showed a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 58%, 92%, 91%, 63% and 73% respectively.

Conclusion:

The FlexPack HP whole blood test showed good specificity but lacked sensitivity. It is not sensitive enough to be used in a general practice setting for the test‐and‐treat approach in the Chinese population.
Review article: pharmacological treatment of the hepatorenal syndrome in cirrhotic patients
Authors: Dagher  , Patch  , Marley  , Moore  , Burroughs
Published: March 2003

Renal failure is common in patients who are dying from end‐stage cirrhosis, developing in 40–80% of all patients. Where there is no anatomical or pathological cause for the renal failure, it is termed the hepatorenal syndrome. When the hepatorenal syndrome develops, it will only recover when there is some degree of improvement in liver function. Thus for most patients this will occur only after liver transplantation, although the transplantation mortality is increased in this group. Hepatorenal syndrome is a common complication of alcoholic hepatitis, and this group is unusual in that with time and abstinence, significant recovery of liver function may occur. There is therefore a need for supportive therapy to allow time for some recovery of liver function in patients with alcoholic hepatitis and hepatorenal syndrome. Similarly, patients may need support whilst waiting for liver transplantation. This article reviews the pathophysiology and treatment of hepatorenal syndrome.
Dose‐dependent effects of ketoprofen on the human gastric mucosa in comparison with ibuprofen
Authors: Donnelly  , Richardson  , Hawkey  , Courtauld  , Stack
Published: March 2003

Background:

As non‐steroidal anti‐inflammatory drugs (NSAIDs) become available for over‐the‐counter use, it is important to define doses that would not cause undue gastroduodenal damage during the short periods for which self‐medication with NSAIDs is licensed.

Aim:

To establish what dose of ketoprofen most closely resembles the maximum dose of ibuprofen (400 mg t.d.s.) licensed for self‐medication.

Methods:

We studied healthy volunteers in a double‐blind double‐dummy randomized crossover study. Each subject took, over four separate 10‐day dosing periods, ibuprofen 400 mg t.d.s., ketoprofen 12.5 mg t.d.s., ketoprofen 25 mg t.d.s. or ketoprofen 50 mg t.d.s. Mucosal injury was assessed by endoscopy at baseline and on the 3rd and 10th day of each dosing period. Ex vivo gastric mucosal prostaglandin (PG) E2 evoked by vortex mixing was measured by radioimmunoassay. Serum thromboxane was also measured by radioimmunoassay.

Results:

Ketoprofen 50 mg t.d.s. suppressed prostaglandin synthesis to a significantly greater extent than ibuprofen and caused significantly more gastroduodenal injury. The profile of prostaglandin synthesis and injury on ketoprofen 12.5 mg t.d.s. most closely resembled that of ibuprofen 400 mg t.d.s.

Conclusions:

Ketoprofen 12.5 mg t.d.s. is an appropriate dose for self‐medication, which is likely to be similar to ibuprofen 400 mg t.d.s. in its effects on the stomach and duodenum.