bluuebunny/crossref_metadata_2025 huggingface dataset:
Eradication of Helicobacter pylori does not decrease the long‐term use of acid‐suppressive medication
Authors: Tan  , Hartog G. Den , Mulder
Published: March 2003

Background

: Many patients are not symptom‐free after eradication therapy for Helicobacter pylori and continue to use proton pump inhibitors or H2‐receptor antagonists (H2‐RAs).

Aim

: To ascertain whether a cohort of patients treated for H. pylori were still taking either proton pump inhibitors or H2‐RAs more than 4 years after H. pylori eradication therapy.

Methods

: In 1993–94, a cohort of 167 patients were given eradication therapy for their H. pylori infection. By means of questionnaires to the patient, general practitioner and pharmacist we were able to retrieve data from 151 patients. The use (at the time of questionnaire) of proton pump inhibitors or H2‐RAs was noted.

Results

: Indications for eradication therapy were peptic ulcer disease: 28 patients (19%) or functional dyspepsia: 123 patients (82%). Mean time of follow‐up was 1466 ± 21 days. In this group, 77 patients (51%) still used acid‐suppressive medication (proton pump inhibitors 44% and H2‐RAs 7%) at the time of the survey (mean follow‐up more than 4 years after eradication). In the group treated for peptic ulcer disease (n=28), only nine patients still used proton pump inhibitors or H2‐RAs. In contrast, 68 patients who were treated for functional dyspepsia (total number 123) still used proton pump inhibitors or H2‐RAs (55%) (P < 0.05).

Conclusion

: Even after successful H. pylori eradication, < 50% of patients stop acid‐suppressive therapy. This contributes significantly to economic cost and raises doubts about the practice of routinely eradicating H. pylori in patients with functional dyspepsia. In contrast, the majority of peptic ulcer patients are able to stop acid‐suppressive medication.
Use of a dried plasma collection card for simplified diagnosis of Helicobacter pylori infection
Authors: Kearney  , Boes  , Peacock
Published: March 2003

Objectives

: To compare testing for Helicobacter pylori IgG antibodies using a dried plasma collection card device with specimens obtained by venepuncture.

Methods

: Eighty‐four patients underwent testing for H. pylori IgG antibodies by venepuncture and by fingerstick using a single drop of blood placed on each of two dried plasma collection card devices. The correlation of venepuncture results to dried plasma card results was assessed.

Results

: There was a high degree of correlation of EIA results between venepuncture and dried plasma card specimens (r=0.98). The qualitative result of the first dried plasma card and venepuncture specimen testing differed in 7 of 84 patients and for the second dried plasma card differed in 7 of 82 patients. The first dried plasma card was 93% sensitive and 100% specific and the second was 93% sensitive and 98% specific as compared to the venepuncture result. There was a high degree of correlation between the first and second dried plasma cards (r=0.996).

Conclusions

: The dried plasma collection card has adequate sensitivity and excellent specificity as compared to venepuncture specimens and is a feasible alternative for H. pylori IgG antibody testing.
Omeprazole, clarithromycin and furazolidone for the eradication of Helicobacter pylori in patients with duodenal ulcer
Authors: Dani  , Queiroz  , Dias  , Franco  , Magalhães  , Mendes  , Moreira  , De Castro  , Toppa  , Rocha  , Cabral  , Salles
Published: March 2003

Aim:

To evaluate the efficacy of omeprazole plus clarithromycin and furazolidone in Helicobacter pylori eradication and duodenal ulcer healing in Brazilian patients.

Methods:

Forty H. pylori‐positive patients with duodenal ulcer were randomized to receive 20 mg omeprazole o.m. or b.d. for 1 month plus 500 mg clarithromycin (b.d.) and 200 mg furazolidone (b.d.) for 1 week.

Results:

Three months after the end of the treatment the eradication rates were 90% by intention‐to‐treat analysis, and 97% by per protocol analysis. Mild side‐effects were observed in 25 patients, none of whom abandoned the protocol. No difference was observed between the 20 mg and 40 mg omeprazole daily doses. Cure or significant improvement of the symptoms and of the histological alterations were observed after H. pylori eradication.

Conclusion:

Our results demonstrate that clarithromycin and furazolidone in combination with omeprazole are a good alternative for H. pylori eradication in Brazilian patients with duodenal ulcer.
Impact of advertisement and clinic populations in symptoms and perception of irritable bowel syndrome
Authors: Lee  , Fitzgerald  , Naliboff  , Schmulson  , Liu  , Fullerton  , Mayer  , Chang
Published: March 2003

Background:

This study assessed the impact of recruitment on irritable bowel syndrome clinical trials, by determining whether irritable bowel syndrome patients recruited from advertisement or a specialty clinic differ in clinical and physiologic measures.

Methods:

We prospectively surveyed 657 irritable bowel syndrome patients who either: (i) were referred from a functional bowel disease clinic (52%); or (ii) responded to advertisement for clinical trials (48%), using questionnaires about bowel and psychological symptoms, and quality of life. In a subset of 42 irritable bowel syndrome patients (29 advertisement and 15 clinic patients), rectal discomfort thresholds were measured before and after repetitive sigmoid stimulation.

Results:

While the advertisement population more commonly consulted primary care physicians, the clinic population more commonly consulted gastroenterologists. The clinic population reported more prevalent and severe abdominal pain, and higher psychological symptom scores, while the advertisement population had greater quality of life. In the visceral perception studies, both subgroups were hypersensitive to rectal distension.

Conclusion:

Compared to the clinic population, the advertisement population had less severe abdominal pain and psychological symptoms, better quality of life but similar visceral perception. The differences in clinical self‐reports may have consequences for enrolment of these different patient populations into clinical trials.
Ursodeoxycholic acid has no influence on function after restorative proctocolectomy in ulcerative colitis
Authors: Tan  , Morton  , Bain  , Keighley
Published: March 2003

Background:

Poor pouch function is associated with impaired bile acid absorption and increased faecal loss of bile acids. Bile acid replacement therapy might therefore be of clinical benefit, provided that diarrhoea is not aggravated by therapy.

Aim:

To investigate the role of exogenous bile acid therapy in patients with poor pouch function after restorative proctocolectomy for ulcerative colitis.

Patients and methods:

Twenty ulcerative colitis patients with poor pouch function (score > 4 on a 12‐point score) were recruited for inclusion to a prospective, randomized, double‐blind crossover, placebo‐controlled trial of ursodeoxycholic acid (10 mg/kg per day in two divided doses for 1 month).

Results:

A total of 16 patients completed the study. There was no significant difference in the functional score or bowel frequency following treatment irrespective of whether the active treatment was given before or after placebo.

Conclusions:

We conclude that ursodeoxycholic acid given over 4 weeks had no influence on functional score or bowel frequency after restorative proctocolectomy for U.C.
Non‐steroidal anti‐inflammatory drugs inhibit Helicobacter pylori‐induced human neutrophil reactive oxygen metabolite production in vitro
Authors: Jones‐Blackett  , Hull  , Davies  , Crabtree
Published: March 2003

Background:

Helicobacter pylori infection is associated with increased production of gastric mucosal reactive oxygen metabolites which have been implicated in mucosal damage and carcinogenesis. In vitro, neutrophils produce reactive oxygen metabolites following activation by H. pylori. Non‐steroidal anti‐inflammatory drugs (NSAIDs) inhibit neutrophil activation by several factors, e.g. N‐formyl‐methionyl‐leucyl‐phenyalanine (f‐MLP).

Aim:

To examine the effect of NSAIDs on H. pylori‐induced reactive oxygen metabolite production by human peripheral blood neutrophils.

Methods:

Neutrophils were stimulated by H. pylori (NCTC 11637) water extract or f‐MLP in the presence or absence of NSAIDs. Reactive oxygen metabolite activity was measured by luminol‐enhanced chemiluminescence.

Results:

H. pylori water extract stimulated a sevenfold increase in chemiluminescence which was inhibited dose‐dependently by diclofenac. All six NSAIDs studied (at 10–4 M) significantly inhibited H. pylori‐and f‐MLP‐stimulated neutrophil reactive oxygen metabolite production. Meclofenamic acid and diclofenac had the greatest inhibitory effects on both H. pylori and f‐MLP‐stimulated neutrophil reactive oxygen metabolite production. The inhibitory effects of other NSAIDs varied with the activation stimulus. NSAIDs did not quench reactive oxygen metabolites generated in a cell‐free xanthine:xanthine oxidase assay.

Conclusion:

Several NSAIDs attenuate H. pylori‐induced neutrophil reactive oxygen metabolites production in vitro. This may be relevant to a potential chemopreventative role in gastric cancer and to a possible lack of synergy between H. pylori and NSAID use regarding peptic ulceration.
Is Helicobacter pylori status relevant in the management of GORD?
Authors: Vigneri S. , Termini R. , Savarino V. , Pace F.
Published: March 2003

There is growing interest in the relationship between H. pylori infection and gastro‐oesophageal reflux disease (GORD). However, this relationship is complex, as yet not fully elucidated, and probably based on a multiplicity of factors. The prevalence of H. pylori infection in patients with GORD is similar, more often lower than in matched controls. There is a negative correlation between H. pylori infection and the severity of GORD. There are many hypothetical mechanisms by which H. pylori infection may protect from the development of GORD. Conversely, there are many possible mechanisms by which H. pylori infection could theoretically foster the GORD. Patients after H. pylori eradication may develop GORD, and this seems to suggest a protective role of H. pylori infection, but other possible explanations include weight gain after H. pylori eradication, changes in dietary habits and smoking, and pre‐existing GORD.

H. pylori infected patients treated by various acid‐inhibiting therapies such as proton pump inhibitors (PPIs), H2‐receptors antagonists (H2‐RA) or vagotomy, have an increase of their corpus gastritis severity, both in the activity of inflammation and in the density of organisms. Long‐term therapy of GORD in H. pylori infected may lead to rapid progression of atrophic gastritis intestinal metaplasia and dysplasia, and increase the risk of developing gastric cancer. More recently it has been shown that H. pylori infection may interfere with the acid suppressive therapies used for treating GORD.

In our opinion the progression of gastritis depends on the threshold of acid output at which H. pylori can ‘flourish’. Recently interest is growing on gastric transitional zones and Helicobacter ecology. Any decrease of acid secretion changes the behaviour of H. pylori: the activity of gastritis improves in the antrum, but it deteriorates in the body. During proton pump inhibitor treatment, H. pylori redistribution occurs within the stomach, from an antral to a corpus or fundus prevalent pattern; corpus‐fundus gastritis, exacerbated by PPI therapy, may result both in a diminished acid secretion and gastro‐oesophageal reflux.

The interest in Barrett's oesophagus is growing due to the associated risk of adenocarcinoma. The literature seems to demonstrate that the prevalence of H. pylori infection of the stomach in Barrett's oesophagus patients is not different from that exhibited by controls, roughly one‐third of the subjects. Intestinal metaplasia of the gastric cardia seems to be equally frequent in patients with and without GORD. Finally, it appears unlikely that a causal relationship exists between H. pylori infection and Barrett's‐associated adenocarcinoma.
A retrospective study of the usefulness of acid secretory testing
Authors: Metz  , Starr
Published: March 2003

Background:

Gastric analysis is useful for diagnosing and monitoring the control of hypersecretory conditions and to distinguish appropriate from inappropriate causes of hypergastrinaemia. Pentagastrin, used to measure maximal acid output (MAO), is no longer available in the USA.

Methods:

We examined the University of Pennsylvania Health System gastric analysis database, which includes demographic data, study indications, gastric analysis, and serum gastrin and secretin testing results according to referral indications, paying specific attention to discordant basal acid output (BAO) and MAO measurements.

Results:

One hundred and twenty‐four gastric analyses were performed in 103 patients (42 males, mean age 47.5 years, 14 with prior acid‐decreasing surgery). Recurrent ulceration or pain unresponsive to antisecretory therapy was the indication in 42 patients. Twelve were hypersecretory, including three each with isolated elevations of BAO or MAO. Hypergastrinaemia was the indication in 35 patients. Five were hypersecretory (four with Zollinger–Ellison syndrome), three had isolated MAO elevations and 16 were hypo‐ or achlorhydric, indicating appropriate hypergastrinaemia. Of the seven patients with isolated MAO elevations, two had clear benefit from the stimulated portion of the study (four additional patients had equivocal benefit).

Conclusions:

Gastrin concentrations cannot be interpreted without knowledge of acid secretory capacity. MAO measurement has a small but significant benefit over measuring BAO alone.
Do mucosal defensive agents improve the cure rate when used with dual or triple therapy regimens for eradicating Helicobacter pylori infection?
Authors: Hojo  , Miwa  , Kikuchi  , Sato
Published: March 2003

Background:

Some of mucosal defensive agents have anti‐Helicobacter pylori activities. However, their effectiveness in eradicating H. pylori infection has not been evaluated.

Aim:

To assess the additive effect of mucosal defensive agents in eradication regimens using statistical analysis.

Methods:

Pertinent studies were retrieved using the Medline and the Igaku–chuo–zasshi databases in Japan, reference and congress abstract lists. Studies in which regimens consisted of dual or triple therapy with mucosal defensive agents and without them, were selected from the retrieved studies. Eradication rates were extracted from studies according to intention‐to‐treat analysis. We evaluated the efficacies of mucosal defensive agents by pooled relative risk of eradication rates and its 95% confidence intervals (95% CI), which were calculated by Mantel–Haenszel method. Heterogeneity among the studies in treatment effect was evaluated by a χ2‐test.

Results:

In dual therapy regimens, mucosal defensive agents demonstrated significant additive effects (pooled relative risk 1.41; 95% CI: 1.24–1.61). In triple therapy regimens, these agents did not provide significant additive effect. The clinical usefulness of specific agents could not be established, when each agent was analysed independently.

Conclusions:

Mucosal defensive agents improve the cure rate when used with existing dual therapy regimens for eradicating H. pylori infection.
Furazolidone versus metronidazole in quadruple therapy for eradication of Helicobacter pylori in duodenal ulcer disease
Authors: Malekzadeh  , Ansari  , Vahedi  , Siavoshi  , Alizadeh  , Eshraghian  , Vakili  , Saghari  , Massarrat
Published: March 2003

Objective:

Furazolidone, an old but cheap antibiotic, was shown to be a good alternative to metronidazole in triple therapy for Helicobacter pylori eradication in areas where metronidazole resistant bacteria are common, but randomized studies are lacking.

Aim:

A randomized controlled trial to determine the efficacy and safety of furazolidone compared to metronidazole in classic quadruple therapy for eradication of H. pylori infection in duodenal ulcer patients.

Methods:

Patients with endoscopically proven duodenal ulcer and positive urease test were randomized to receive ranitidine 300 mg, amoxycillin 1000 mg and bismuth subcitrate 240 mg b.d, with either furazolidone 200 mg b.d (RABF), or metronidazole 500 mg b.d. (RABM) for 2 weeks. Compliance and side‐effects were monitored and recorded by table diary. H. pylori eradication was assessed at least 4 weeks after the completion of therapy with 14C‐urea breath test.

Results:

A total of 106 patients were enrolled and 101 (59 male, 42 female, mean age=40 ± 11 years) completed the study. Endoscopic findings and demographic data were comparable in both groups. Intention‐to‐treat eradication rates were 75% and 55% (P=0.03) and per protocol eradication rates were 82 and 56% (P=0.006) in the RABF and RABM groups, respectively. Side‐effects were reported by 13 patients (27%) in the RABF group (one stopped treatment) compared to five patients (10%) in the RABM group (P=0.04).

Conclusion:

Quadruple therapy containing furazolidone, instead of metronidazole, results in a significantly higher H. pylori eradication rate in Iranian duodenal ulcer patients.
Rifabutin‐based ‘rescue therapy’ for Helicobacter pylori infected patients after failure of standard regimens
Authors: Perri  , Festa  , Clemente  , Quitadamo  , Andriulli
Published: March 2003

Background:

The ideal treatment for patients who have failed eradication of Helicobacter pylori infection after standard proton pump inhibitor‐based triple therapies has still to be determined. Although either a second course of triple therapy or a quadruple therapy (proton pump inhibitor plus bismuth‐based triple therapy) has been proposed, the efficacy of these second‐line therapies is relatively unknown. Therefore, alternative strategies are needed.

Aim:

To assess the efficacy and tolerability of rifabutin, a derivative of rifamycin‐S, in patients who were still H. pylori infected after two or more courses of 1‐week triple therapies.

Methods:

Patients were given a 1‐week regimen of pantoprazole 40 mg b.d. + amoxycillin 1 g b.d. + rifabutin 300 mg daily. Side‐effects and compliance were determined at the end of therapy. Eradication rate was assessed with a 13C‐urea breath test performed at 4 and 12 weeks after treatment.

Results:

Forty‐one patients (mean age 47 ± 15 years) were studied. All patients took medications according to the proposed schedule. Side‐effects were infrequent and mild. The eradication rates were 71% (95% CI: 57–85%) on intention‐to‐treat analysis and 74% (95% CI: 61–88%) on per protocol analysis.

Conclusions:

Rifabutin, in combination with pantoprazole and amoxycillin, is an effective and well tolerated regimen in patients who failed standard eradication treatments.
Diagnosis of Helicobacter pylori after triple therapy in uncomplicated duodenal ulcers—a cost‐effectiveness analysis
Authors: Gené  , Calvet  , Azagra
Published: March 2003

Background:

The cost‐effectiveness of determining Helicobacter pylori status after treatment remains to be established.

Aim:

To determine the benefit of post‐treatment assessment of H. pylori eradication in patients with uncomplicated duodenal ulcer.

Materials and methods:

A decision analysis was performed in patients with uncomplicated duodenal ulcer who were H. pylori‐positive and had received eradication therapy. A decision tree was devised to compare the costs per patient of two different strategies: (a) systematic performance of post‐treatment urea breath test and new treatment if positive; and (b) clinical follow‐up, 13C‐urea breath test if dyspeptic symptoms recurred and eradication treatment if the test was positive.

Results:

Post‐eradication 13C‐urea breath test was notably more expensive than clinical follow‐up, both in a low‐cost per care setting (197 vs. 132 Euros) and in a high‐cost per care (614 vs. 340 US $) scenario. This conclusion remained stable for a wide range of variations of the variables included in the decision tree (e.g. cure rates of eradication treatment, cost of the urea breath test or sensitivity, and specificity of urea breath test to detect eradication).

Conclusion:

In patients with uncomplicated duodenal ulcer, evaluation of eradication after H. pylori treatment markedly increases costs with no clear improvement in results and therefore should not be performed routinely.
Randomized study comparing omeprazole with ranitidine as anti‐secretory agents combined in quadruple second‐line Helicobacter pylori eradication regimens
Authors: Michopoulos  , Tsibouris  , Bouzakis  , Balta  , Vougadiotis  , Broutet  , Kralios
Published: March 2003

Background:

Few data are available on the efficacy of second‐line H. pylori eradication regimens.

Aim:

To compare the efficacy of either omeprazole or ranitidine in a second‐line quadruple regimen in patients with duodenal ulcer or erosive duodenitis.

Patients and methods:

A total of 37 patients with erosive duodenitis and 119 with duodenal ulcer who have failed eradication of H. pylori with double or triple regimens, without metronidazole, were randomly assigned to receive tripotassium dicitrato bismuthate 600 mg t.d.s. + metronidazole 500 mg t.d.s. + tetracycline hydrochloride 500 mg t.d.s. combined with either omeprazole 20 mg b.d. (group O, 78 patients) or ranitidine 300 mg b.d. (group R, 78 patients) for 14 days. H. pylori eradication was verified by histology, rapid urease test and 13C‐urea breath test.

Statistics:

t‐test, χ2‐test.

Results:

A total of 143 patients had a post‐treatment endoscopy. Eradication rates were: intention‐to‐treat: group O 77% (67–87), group R 76% (66–85), P=0.85; per protocol analysis: group O 86% (77–95), group R 82 (71–93), P=0.58. Side‐effects were frequent but mild.

Conclusions:

Omeprazole 20 mg b.d. and ranitidine 300 mg b.d. were equally effective as antisecretory agents combined in a second‐line quadruple eradication regimen.
A new highly effective short‐term therapy schedule for Helicobacter pylori eradication
Authors: Zullo  , Rinaldi  , Winn  , Meddi  , Lionetti  , Hassan  , Ripani  , Tomaselli  , Attili
Published: March 2003

Background:

Although triple therapy regimens suggested in the Current European guidelines give fairly good results, several studies have reported an unsatisfactory Helicobacter pylori eradication rate (< 80%).

Aim:

To evaluate the efficacy of a new short‐term treatment sequence on H. pylori eradication.

Methods:

A total of 52 patients with H. pylori infection and either non‐ulcer dyspepsia (34 patients) or peptic ulcer (18 patients) were enrolled to receive a 10‐day therapy: omeprazole 20 mg b.d. plus amoxycillin 1 g b.d. for the first 5 days, followed by omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for the remaining 5 days. H. pylori infection at entry was assessed by rapid urease test and histology on biopsies from the antrum and the corpus. Bacterial eradication was assessed by endoscopy (peptic ulcer patients) or 13C urea breath test (non‐ulcer dyspepsia patients) 4–6 weeks after therapy had ended.

Results:

All patients completed the study. H. pylori eradication was achieved in all but one patient, with an eradication rate of 98% (95% CI: 94.3–100) with intention‐to‐treat analysis. Patient compliance was good (consumption of prescribed drugs > 95%) for all but one patient, who took the triple therapy regimen for 4 days instead of 5 days. No major side‐effects were reported but three (6%) patients complained of mild side‐effects.

Conclusions:

The use of this ‘five plus five’ therapy schedule as an initial treatment for H. pylori deserves further investigation.
Effects of fedotozine on gastric emptying and upper gastrointestinal symptoms in diabetic gastroparesis
Authors: Jones  , Wishart  , Berry  , Abitbol  , Horowitz
Published: March 2003

Background:

Delayed gastric emptying and upper gastrointestinal symptoms occur frequently in patients with diabetes mellitus.

Aim:

To evaluate the effects of fedotozine on gastric emptying and gastrointestinal symptoms in diabetic gastroparesis.

Methods:

Thirty‐one diabetic patients (20 type 1, 11 type 2) with gastroparesis were randomized to receive fedotozine (30 mg as the tartrate) or placebo t.d.s. Measurements of gastric emptying (100 g ground beef labelled with 20 MBq 99mTc‐sulphur colloid chicken liver and 150 mL 10% dextrose labelled with 10 MBq 113mIn‐DTPA) and gastrointestinal symptoms were performed before and after 12–16 days of treatment. Data are the mean ± s.d.

Results:

Of the 31 patients enrolled, two were excluded from analysis. Data from the remaining 29 patients (18 type 1, 11 type 2; 22 female, seven male), aged 42.7 ± 11.1 years (of whom 14 were randomized to fedotozine and 15 to placebo), were analysed. Fedotozine had no effect on either gastric emptying (solid retention at 100 min; fedotozine: baseline, 84 ± 15%; treatment, 73 ± 23% vs. placebo: baseline, 83 ± 10%; treatment, 70 ± 20%) or liquid 50% emptying time (fedotozine: baseline, 59 ± 32 min; treatment, 58 ± 38 min vs. placebo: baseline, 44 ± 9 min; treatment, 43 ± 21 min) or gastrointestinal symptoms (fedotozine: baseline, 4.4 ± 2.9; treatment, 4.1 ± 3.9 vs. placebo: baseline, 4.9 ± 4.2; treatment, 4.8 ± 3.9).

Conclusions:

Fedotozine has no effect on gastric emptying in patients with diabetic gastroparesis.
Motilides accelerate regional gastrointestinal transit in the dog
Authors: Chiba  , Thomforde  , Kost  , Allen  , Phillips
Published: March 2003

Background:

Motilides have prokinetic effects on the upper gut during fasting, increasing the strength of antral contractions and stimulating gastroduodenal phase 3 sequences. Effects on the distal gut, and postprandially, are less well documented.

Aim:

To evaluate dose–response effects of motilin and erythromycin on gastric emptying, small bowel and colonic transit in the dog using a validated scintigraphic technique.

Methods:

For gastric emptying and small bowel transit, 99mTc labelled beads were added to a meal of dog chow (450 kcal). Regional colonic transit was measured by 111In labelled beads placed in a capsule which dissolved and released radiation into the proximal colon. Scintiscans were taken at regular intervals and indices of whole‐gut transit were calculated. Drugs were given by slow intravenous administration.

Results:

In the doses used, motilin accelerated regional colonic transit but did not hasten gastric emptying or small bowel transit. Single or repeated doses of motilin had similar effects on colonic transit. Erythromycin accelerated gastric emptying, small bowel transit and regional colonic transit.

Conclusions:

Motilin receptors are apparently present in the canine small bowel and colon. Postprandially, motilides accelerate transit in the distal gut.
Oral pharmacokinetics of omeprazole and lansoprazole after single and repeated doses as intact capsules or as suspensions in sodium bicarbonate
Authors: Sharma  , Peyton  , Spears  , Raufman  , Howden
Published: March 2003

Background:

Omeprazole and lansoprazole can be given in sodium bicarbonate as, respectively, simplified omeprazole suspension and simplified lansoprazole suspension. We previously found the antisecretory effect of omeprazole 20 mg given as simplified omeprazole suspension to be lower than with intact capsules. However, lansoprazole 30 mg as simplified lansoprazole suspension produced an effect similar to that seen with intact capsules.

Aim:

To evaluate the absorption of both drugs when given orally as capsules or as suspensions in sodium bicarbonate.

Methods:

In random order, we gave 5‐day courses of omeprazole 20 mg and lansoprazole 30 mg as capsules and as suspensions in sodium bicarbonate to 12 healthy women. Serial blood samples were taken on days 1 and 5 of each course for pharmacokinetic measurements.

Results:

There was impairment of omeprazole absorption when given as simplified omeprazole suspension. Maximum plasma concentration and area under the concentration/time curve were lower with simplified omeprazole suspension than with omeprazole capsules (P=0.034 and 0.013, respectively, on day 5). No differences were found in lansoprazole absorption when simplified lansoprazole suspension was compared with its standard capsule formulation. Relative bioavailability of omeprazole from simplified omeprazole suspension compared to the capsule was 58.4% on day 5. The corresponding value for lansoprazole was 84.7%.

Conclusions:

Simplified omeprazole suspension 20 mg does not supply adequate omeprazole for systemic absorption. Lansoprazole absorption from simplified lansoprazole suspension is maintained.
Review article: treatment of Helicobacter pylori infection with ranitidine bismuth citrate‐ or proton pump inhibitor‐based triple therapies
Authors: Van Oijen A. H. A. M. , Verbeek A. L. , Jansen J. B. M. J. , De Boer W. A.
Published: March 2003

Triple therapy, combining a proton pump inhibitor with clarithromycin (C) and either amoxycillin (A) or a nitro‐imidazole (I) is the standard in Helicobacter pylori eradication therapy. Recently, triple therapies based on ranitidine bismuth citrate (RBC) have emerged as an alternative. This review examines the current literature for studies directly comparing proton pump inhibitor‐ with RBC‐based triple therapies. Seventeen studies were identified, of which three have been published as a full paper.

Eradication rates in an intention‐to‐treat analysis ranged from 51 to 98%. No large difference in cure rates between the different regimens was demonstrated, although the RBC‐I‐C combination was somewhat superior. No definite conclusions could be made about the impact of metronidazole or clarithromycin resistance since only three studies performed a formal resistance analysis. No serious side‐effects were reported, and dropout rates were equal for the two regimens.

Both RBC‐ and proton pump inhibitor‐based triple therapies are highly effective. If one prefers a imidazole/clarithromycin combination the evidence presented here suggests that RBC should be used instead of a proton pump inhibitor. Larger studies comparing both forms of triple therapy, using proper resistance analysis, are needed before final conclusions can be reached regarding efficacy in the setting of bacterial resistance.
Esomeprazole provides improved acid control vs. omeprazole in patients with symptoms of gastro‐oesophageal reflux disease
Authors: Lind  , Rydberg  , Kylebäck  , Jonsson  , Andersson  , Hasselgren  , Holmberg  , Röhss
Published: March 2003

Background:

Esomeprazole (Nexium) is a new proton pump inhibitor for the treatment of acid‐related diseases.

Methods:

In this double‐blind crossover study, 38 patients with gastro‐oesophageal reflux disease (GERD) symptoms were randomized to esomeprazole 40 and 20 mg and omeprazole 20 mg once daily for 5 days. On day 5 of each dosing period, 24‐h intragastric pH and pharmacokinetic variables were measured.

Results:

Thirty‐six patients aged 29–58 (mean 45) years completed the study. Esomeprazole 40 and 20 mg maintained intragastric pH > 4 for (mean) 16.8 and 12.7 h, respectively, vs. 10.5 h for omeprazole 20 mg (P < 0.001 and P < 0.01). Twenty‐four‐hour median intragastric pH was significantly higher with esomeprazole 40 mg (4.9) and 20 mg (4.1) than with omeprazole 20 mg (3.6) (P < 0.001 and P < 0.01). Area under the plasma concentration–time curve (AUC) was 80% higher for esomeprazole 20 mg vs. omeprazole, while that for esomeprazole 40 mg was more than five times higher (each P < 0.0001). Interpatient variability in intragastric pH and AUC was less with esomeprazole than with omeprazole. Esomeprazole was well tolerated and there were no safety concerns.

Conclusions:

Esomeprazole provides more effective acid control than omeprazole, with reduced interpatient variability, thereby offering the potential for improved efficacy in acid‐related diseases.
Effects of iron and iron chelation in vitro on mucosal oxidant activity in ulcerative colitis
Authors: Millar  , Rampton  , Blake
Published: March 2003

Background:

Reactive oxygen species may be pathogenic in ulcerative colitis. Oral iron supplements anecdotally exacerbate inflammatory bowel disease and iron levels are elevated in the inflamed mucosa. Mucosal iron may enhance hydroxyl ion production via Fenton chemistry. Conversely, the iron chelator, desferrioxamine, is reportedly beneficial in Crohn’s disease.

Aims:

To assess the in vitro effects of exogenous iron and of iron chelators on the production of reactive oxygen species by colonic biopsies from normal control subjects and patients with ulcerative colitis.

Methods:

Luminol‐amplified chemiluminescence was used to measure mucosal reactive oxygen species production both before and after addition in vitro of ferric citrate (100 μM), desferrioxamine (1 m
M) and 1,10‐phenanthroline (1 m
M).

Results:

Ferric citrate had no effect on the chemiluminescence produced by human colonic mucosa. However, desferrioxamine and phenanthroline reduced chemiluminescence by 47% (n=7, P=0.018) and by 26% (n=10, P=0.005), respectively, in inactive ulcerative colitis, and by 44% (n=9, P=0.008) and 42% (n=11, P=0.006) in active disease.

Conclusion:

The lack of effect of ferric citrate suggests that sufficient free iron is already present in inflamed biopsies to drive the Fenton reaction maximally. The effects of desferrioxamine and 1,10‐phenanthroline on the chemiluminescence of biopsies from patients with ulcerative colitis suggest that a clinical trial of topical iron chelation in active disease is indicated.
Third line treatment for Helicobacter pylori: a prospective, culture‐guided study in peptic ulcer patients
Authors: Gomollón F. , Sicilia B. , Ducóns J. A. , Sierra E. , Revillo M. J. , Ferrero M.
Published: March 2003

Background:

A third line treatment is needed in roughly 5% of patients infected with Helicobacter pylori. Few data have been reported on efficacy of treatment regimens in these patients.

Methods:

A prospective trial was designed to study the effectiveness of third line treatment of H. pylori infection in ulcer patients. Two‐week quadruple, culture‐guided, combinations were used in 31 consecutive patients. Susceptibility to metronidazole and clarithromycin were studied by E‐test, and thereafter a predetermined treatment regimen was used. Compliance was evaluated by pill count, and eradication defined by negative urea breath test at 6 weeks.

Results:

Two main quadruple regimens were used in 29 patients. In spite of good compliance, the combination of omeprazole, tetracycline, bismuth and clarithromycin (OTBC) showed an eradication rate (per protocol analysis) of 36% (five out of 14; CI: 12.8–64.9), and if amoxycillin was used (OTBA) the rate was 67% (eight out of 12; CI: 34.9–90.1). The difference was not significant. No clinical factor was found to be associated with failure to eradicate.

Conclusions:

Third line treatment often fails to eradicate H. pylori infection. New strategies need to be developed and tested for this common clinical situation.
Efficacy of two one‐week rabeprazole/levofloxacin‐based triple therapies for Helicobacter pylori infection
Authors: Cammarota G. , Cianci R. , Cannizzaro O. , Cuoco L. , Pirozzi G. , Gasbarrini A. , Armuzzi A. , Zocco M. A. , Santarelli L. , Arancio F. , Gasbarrini G.
Published: March 2003

Background:

One‐week low‐dose proton pump inhibitor‐based triple therapies have usually proved to be effective treatments for Helicobacter pylori infection.

Aim:

To investigate the eradication efficacy, safety profile and patient compliance of two triple therapies containing a standard dose of rabeprazole and a new fluoroquinolone, levofloxacin.

Methods:

One hundred patients referred to us for gastroscopy, who were H. pylori‐positive, were consecutively recruited in a prospective, open‐label study. The enrolled patients were randomised to receive a seven‐day course of rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and either amoxycillin 1 g b.d. (RLA group) or tinidazole 500 mg b.d. (RLT group). Their H. pylori status was assessed by means of histology and rapid urease test at entry, and by 13C‐urea breath test 8 weeks after the end of treatment.

Results:

All 100 enrolled patients completed the study. Forty‐six of 50 patients treated with RLA (both PP and ITT analysis: 92%; 95% CI: 81–98%) and 45 of 50 with RLT (both PP and ITT analysis: 90%: 95% CI: 78–97%), became H. pylori‐negative. Slight or mild side‐effects occurred in 4 (8%) patients of the RLA group and in 5 (10%) of the RLT group.

Conclusions:

This study demonstrates the efficacy of two 1‐week rabeprazole‐based triple therapies including levofloxacin to eradicate H. pylori. These regimens prove to be safe, well‐tolerated, and achieved good eradication rates. Levofloxacin may be an effective alternative to clarithromycin in triple therapy regimens.
A randomized trial of polyurethane and silicone percutaneous endoscopic gastrostomy catheters
Authors: Van Den Hazel S. J. , Mulder C. J. J. , Den Hartog G. , Thies J. E. , Westhof W.
Published: March 2003

Background:

No data are available on differences in complication rate and long‐term functioning between polyurethane and silicone percutaneous endoscopic gastrostomy (PEG) catheters.

Methods:

We randomized patients who qualified for PEG placement to receive either a polyurethane or silicone PEG catheter. Patients were prospectively monitored for 28 days after placement for the occurrence of complications. Data on long‐term PEG survival were obtained retrospectively from the Hospital and general practitioner’s medical records.

Results:

One hundred and six patients were randomized (polyurethane 50, silicone 56). During the first four weeks of follow‐up, major complications occurred twice with both polyurethane and silicone PEGs (relative risk 1.1, 95% confidence interval: 0.11–11). Overall complications occurred four times with polyurethane and 17 times with silicone PEGs (relative risk 3.8, 95% confidence interval: 1.37–10.5). Long‐term follow‐up was available in 96 patients. Seven polyurethane PEGs and 10 silicone PEGs were removed because of PEG malfunctioning, the remainder functioned well until death or the reinstitution of oral feeding. The median complication‐free survival was 916 days for the polyurethane PEG and 354 days for the silicone PEG (Log rank test: P=0.24).

Conclusion:

Polyurethane PEG catheters were associated with less short‐term complications than silicone catheters, but major complications and long‐term function were comparable.
Serum transforming growth factor‐β1 levels increase in response to successful anti‐inflammatory therapy in ulcerative colitis
Authors: Sambuelli A. , Diez R. A. , Sugai E. , Boerr L. , Negreira S. , Gil A. , Camartino G. , Huernos S. , Doldán I. , Felstiner D. , Bai J. C.
Published: March 2003

Objective:

To investigate serum levels of transforming growth factor‐β1 and interferon‐γ in active ulcerative colitis and to assess changes during treatment.

Methods:

We prospectively evaluated serum from 25 patients with untreated active ulcerative colitis and 19 healthy controls. Disease activity score (DAI), serum transforming growth factor‐β1 and interferon‐γ levels were measured at baseline and after 7 days of conventional treatment. Disease activity score and transforming growth factor‐β1 were also assessed at 42 days.

Results:

Baseline transforming growth factor‐β1 levels were significantly higher in patients than in controls (P < 0.02). On the 7th day, transforming growth factor‐β1 levels increased only in patients who responded (P < 0.01); variations in transforming growth factor‐β1 levels and disease activity score were inversely correlated (r=– 0.72, P < 0.001). At day 42, serum transforming growth factor‐β1 decreased significantly compared with the 7th day (P < 0.05). While in controls, interferon‐γ was undetectable; untreated patients had higher, widely variable, levels. At day 7, responders had higher interferon‐γ values than unresponsive cases. Variations in interferon‐γ correlated moderately with changes in transforming growth factor‐β1 (r=0.53, P < 0.05). Cytokine response did not depend upon the type of treatment.

Conclusions:

Both transforming growth factor‐β1 and interferon‐γ may play a role in the injury–repair process in active ulcerative colitis. Variations in circulating transforming growth factor‐β1 levels in the first week of treatment seem to be related to the therapeutic response.
Review article: the role of non‐acid reflux in gastro‐oesophageal reflux disease
Authors: Katz P. O.
Published: March 2003

The role of acid in the pathogenesis of gastro‐oesophageal reflux disease (GERD) has been extensively studied and is well accepted. The role, if any, of non‐acid reflux, in particular duodenogastro‐oesophageal reflux, is much debated. The availability of new technology to detect non‐acid reflux has heightened interest in this question. This article reviews the following: How do we define non‐acid reflux? Does duodenogastro‐oesophageal reflux (alone or in combination) cause oesophageal injury, symptoms or both? What is its role in complicated GERD? What methods are available to assess non‐acid reflux? Does non‐acid reflux need treatment and if so what modalities are available?
A lyophilized and inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates
Authors: Canducci F. , Armuzzi A. , Cremonini F. , Cammarota G. , Bartolozzi F. , Pola P. , Gasbarrini G. , Gasbarrini A.
Published: March 2003

Background:

Acid suppression plus two antibiotics is considered the reference anti‐Helicobacter pylori treatment. Reported eradication rates are around 65–80%. Human Lactobacillus acidophilus shows an in vitro inhibitory effect on the attachment of H. pylori to gastric epithelial cell lines. Culture supernatant of this bacillus seems to decrease the in vitro viability of H. pylori.

Aim:

To evaluate whether the supplementation with an inactivated preparation of L. acidophilus could improve the efficacy of a standard anti‐H. pylori therapy.

Methods:

One‐hundred and twenty H. pylori‐positive patients were randomly assigned to a 7‐day triple therapy based on rabeprazole (20 mg b.d.), clarithromycin (250 mg t.d.s.) and amoxicillin (500 mg t.d.s.) (RCA group: 60 subjects), or to the same regimen supplemented with a lyophilized and inactivated culture of Lactobacillus acidophilus (t.d.s.) (RCAL group: 60 subjects).

Results:

In the RCA group, eradication was successful in 72% (42 out of 58 patients) from a per protocol (PP) analysis, or 70% (42 out of 60 patients) using an intention‐to treat (ITT) analysis. In the RCAL group a significant increase in the eradication rate was observed: 88% (52 out of 59 patients) from PP analysis (P=0.03), 87% (52 out of 60 patients) from ITT analysis (P=0.02).

Conclusions:

These results seem to confirm the in vitro anti‐H. pylori effect of L. acidophilus, suggesting that the inactivated L. acidophilus could be effective in increasing eradication rates of a standard anti‐H. pylori therapy.
One‐week triple therapy with esomeprazole provides effective eradication of Helicobacter pylori in duodenal ulcer disease
Authors: Veldhuyzen Van Zanten S. , Lauritsen K. , Delchier J.‐C. , Labenz J. , De Argila C. M. , Lind T. , Treichel H.‐C. , Stubberöd A. , Cockeram A. , Hasselgren G. , Göthe L. , Wrangstadh M. , Sinclair P.
Published: March 2003

Background:

Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid‐related diseases.

Methods:

Four hundred and forty eight duodenal ulcer patients with Helicobacter pylori infection, confirmed by 13C‐urea breath test (UBT), and no current ulcer, were randomised to double‐blind treatment with esomeprazole 20 mg twice daily (b.d.) (n=224) or omeprazole 20 mg b.d. (n=224), in combination with amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week (EAC and OAC, respectively). A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H. pylori eradication.

Results:

Intention‐to‐treat (ITT) analysis comprised 400 patients (EAC, n=204; OAC, n=196) and per protocol (PP) analysis 377 patients (EAC, n=192; OAC, n=185). Eradication rates (95% confidence intervals) for ITT and PP populations were: EAC, 90% (85–94%) and 91% (86–94%); OAC, 88% (82–92%) and 91% (86–95%). Between‐group differences in eradication rates were not statistically significant. Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy.

Conclusions:

Esomeprazole‐based triple therapy for 1 week is highly effective in eradicating H. pylori infection in duodenal ulcer disease, offers comparable efficacy to omeprazole‐based therapy, and is well tolerated.
Effect of activin on cell growth in primary cultures of guinea pig gastric epithelial cells
Authors: Ogihara S. , Kudo T. , Yamada M. , Seki T. , Kawaguchi M. , Saito T.
Published: March 2003

Background: The effect of activin on differentiated cells is known to be different from that on undifferentiated cells. Cultured gastric epithelial cells in complete serum‐free conditions grew into matured mucous cells after treatment with epidermal growth factor (EGF).

Aim: To elucidate the effect of activin on the growth of differentiated and undifferentiated gastric mucosal cells.

Methods: Cultured guinea pig gastric epithelial cells were prepared using the method of Ogihara et al.
1Synthesis of activin was analysed by Western blot using monoclonal anti‐activin A antibody. Cell proliferation was assessed by counting the number of cells. Mucin production was assessed by histochemical study using periodic acid‐Schiff (PAS) reaction.

Results: Western blot analysis indicated that activin was synthesized in cultured guinea pig gastric mucosal cells. One hundred nanomolar EGF induced a 3‐fold increase in cell count and the appearance of PAS‐positive granules. Five nanograms activin per millilitre without EGF stimulated proliferation of the cells that showed almost negative PAS staining. When activin was added after treatment with 100 n
m EGF for 24 h, cell proliferation induced by EGF was inhibited by activin at concentrations higher than 5 ng/mL.

Conclusion: These results suggest that activin stimulates proliferation of undifferentiated cells and inhibits growth of differentiated cells.
Helicobacter pylori and NSAID gastropathy
Authors: Lazzaroni M. , Bianchi porro G.
Published: March 2003

Non‐steroidal anti‐inflammatory drugs (NSAIDs) and Helicobacter pylori are known to share a number of pathogenic mechanisms, but there is no evidence to show a significant synergic action between the two risk factors. Studies assessing this subject have differed in almost every aspect of their methodology, including the definition of a NSAID user as well as the types, doses, duration and their indications for NSAID use. They also differed in their end‐points, the definition of dyspepsia and the regimes used for eradication of H. pylori. However, some conclusions may be drawn from the results of clinical trials.

In H. pylori‐positive patients without mucosal lesions, NSAIDs may aggravate dyspeptic symptoms but, with the exception of elderly patients, they do not present a definite major risk of gastric and duodenal lesions and, above all, of ulcer‐correlated complications.

So what recommendations can be made with regard to H. pylori eradication in patients requiring treatment with NSAIDs? The microorganism and the anti‐inflammatory drugs are undoubtely independent causes of gastric and duodenal damage. Patients taking NSAIDs who are found to have gastric or duodenal ulcers should therefore be tested for the bacterium and specifically treated, since H. pylori and NSAID‐induced ulcers may be macroscopically indistinguishable.

Whether asymptomatic patients taking NSAIDs should be tested and treated for H. pylori infection is still a matter of debate.