bluuebunny/crossref_metadata_2025 huggingface dataset:
Pantoprazole‐based 10‐day triple therapy is effective in Helicobacter pylori eradication
Authors: Bardhan  , Morton  , Slater  , Perry  , Cherian  , Jones  , Brookes  , Thompson  , Morris  , McCaldin
Published: March 2003

Aim:

To investigate the efficacy of a short course of pantoprazole‐based triple therapy in Helicobater pylori eradication in a single‐centre pilot study.

Methods:

Patients with active or healed duodenal ulcer or with gastric erosions or gastritis, all of whom were H. pylori‐positive, received 10 days of twice‐daily open treatment with pantoprazole 40 mg, plus clarithromycin 250 mg and tinidazole 500 mg. H. pylori was assessed at entry and 28–35 days after the end of treatment by rapid urease test (at entry only), culture and antimicrobial sensitivity, histology and 13C urea breath test. The criterion for eradication was a negative result in all three tests.

Results:

Seventy patients were treated, of whom four were excluded from analysis due to major deviations from the study protocol. Eradication of H. pylori was achieved in 57/66 patients (per protocol analysis 86% (95% CI: 78–95%)) and was higher in patients with organisms sensitive to nitroimidazole before treatment (sensitive: 47/53 (89%), insensitive: 10/13 (77%)). There was marked reduction in acute gastritis throughout the stomach while chronic gastritis decreased only in the corpus. Healing was achieved in all 24 patients with active duodenal ulcer. Treatment was complied with; only one patient missed one of the 20 doses. Adverse events were of mild or moderate intensity and did not require withdrawal from treatment.

Conclusion:

A short course of pantoprazole‐based triple therapy is well tolerated and effective in eradicating H. pylori.
Clinical economics review: gastrointestinal complications of non‐steroidal anti‐inflammatory drugs
Authors: Haslock
Published: March 2003

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are the most widely used symptomatic remedies for rheumatic disorders. Their major side‐effects involve the gastrointestinal tract and, while the stomach is often the prime focus of adverse reactions, the whole gut may be involved. A number of strategies have been used to reduce both the incidence of side‐effects and their economic consequences. Decreased NSAID use can be achieved both by rational prescribing and by active promotion of other, usually non‐pharmacological, methods of controlling symptoms. Prescribing NSAIDs based on their cost assumes all have equal efficacy and side‐effects, which is demonstrably untrue. Picking the least toxic NSAID is more logical. Most of the larger studies and meta‐analyses available concentrate on older NSAIDs and risk overlooking the advantages of newer preparations which have been shown to be cost beneficial by more comprehensive economic analyses. Misoprostol prophylaxis has been the subject of a number of economic evaluations which, until recently, were based on extrapolations rather than clinical data. There are now good clinical data available which show a small but significant reduction in major side‐effects at the expense of an increase in minor but unpleasant ones. Proton pump inhibitors appear to offer the same degree of gastroprotection as misoprostol, with the additional benefit of symptom relief. Economic data regarding the costs and benefits of prophylaxis with proton pump inhibitors are not yet available. There is still a need for a more comprehensive evaluation of the benefits of NSAIDs in different clinical situations to balance against the costs of adverse reactions.
Dose–response relationship of lansoprazole to gastric acid antisecretory effects
Authors: Blum  , Hunt  , Kidd  , Shi  , Jennings  , Greski‐Rose
Published: March 2003

Background:

Proton pump inhibitors have been found to be effective in numerous studies in patients with peptic ulcer disease, particularly associated with Helicobacter pylori and gastro‐oesophogeal reflux disorders. Optimal healing rates of antisecretory therapy for peptic acid disease is dependent upon the degree and duration of acid suppression and the length of treatment.

Objective:

To evaluate the extent and duration of gastric acid suppression of several lansoprazole regimens, administered for 5 consecutive days in 32 healthy adult male subjects.

Methods:

Intragastric 24‐h pH monitoring was performed in 32 healthy subjects in a randomized, double‐blind, four‐way crossover study. Sixteen subjects (Group 1) received lansoprazole 30 mg o.d. (once daily), 15 mg b.d. (twice daily), 30 mg b.d. and 30 mg t.d.s. (three times a day) for 5 days; and 16 subjects (Group 2) received lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. for 5 days.

Results:

Mean 24‐h intragastric pH values for lansoprazole 30 mg o.d., 15 mg b.d., 30 mg b.d. and 30 mg t.d.s. were 4.47, 4.57, 5.07 and 5.63, respectively. Multiple‐dose regimens of lansoprazole 30 mg b.d. and t.d.s. produced greater acid suppression compared to lansoprazole 30 mg o.d. and 15 mg b.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 15 mg b.d. Mean 24‐h intragastric pH values for lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. were 4.13, 4.45, 5.19 and 5.13, respectively. Multiple‐dose regimens of lansoprazole 60 mg b.d. and t.d.s. produced significantly greater acid suppression compared to lansoprazole 30 mg o.d. and 60 mg o.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 60 mg o.d. Lansoprazole 30 mg t.d.s., 60 mg b.d. and 60 mg t.d.s. produced significantly greater percentage time above pH 3, 4, 5 and 6 than did lansoprazole 30 mg o.d. Post‐regimen serum gastrin values increased by 50–130% from pre‐study mean values but remained within normal range and returned to pre‐study values 7–14 days post‐dosing.

Conclusions:

Multiple‐dose regimens of lansoprazole (≥30 mg b.d. for 5 days) produce significantly increased intragastric pH and significantly longer duration of increased intragastric pH than does lansoprazole 30 mg administered once daily.
Screening for Helicobacter pylori in young dyspeptic patients referred for investigation—endoscopy for those who test negative
Authors: Breslin  , Lee  , Buckley  , O’morain
Published: March 2003

Background:

Studies in young dyspeptic patients have suggested that screening strategies based on non‐invasive H. pylori testing can reduce endoscopy workload by 25–40%. Such strategies usually propose that only H. pylori‐positive individuals should undergo endoscopy. This approach may fail to diagnose idiopathic ulcers, ulcers in patients whose screening test is falsely negative and reflux disease.

Aim:

To investigate a hypothetical screening strategy in which endoscopy is initially performed only in H. pylori‐negative dyspeptics.

Methods:

Seventy‐two consecutive patients under 45 years of age undergoing investigation for ‘ulcer‐like’ dyspepsia had invasive and non‐invasive determination of H. pylori status. Individuals found to be H. pylori‐positive at endoscopy received 1 week of proton pump inhibitor‐based triple therapy. H. pylori‐negative individuals received therapy tailored to their diagnosis. Endoscopy was repeated in the positive group to confirm successful eradication. Results were analysed according to our strategy, i.e. serologically‐positive patients would have received eradication therapy without endoscopy, but patients found to be negative would have been referred for endoscopy.

Results:

According to the serology test there were 39 positive and 33 negative results. Symptoms failed to resolve during follow‐up in nine of the serological positives despite successful eradication. There were also five false positives who were deemed likely treatment failures. Thus according to our strategy, these 14 serologically‐positive patients would ultimately have required an endoscopy and the other 25 serologically‐positive patients would have avoided an endoscopy, resulting in a 35% reduction in endoscopy usage in this population. In the serologically‐negative group there were three cases of peptic ulcer disease where the test was falsely negative, but they were detected by the strategy. No cases of gastric malignancy were detected at endoscopy. Thus our strategy would have reduced initial endoscopy referrals by 35% in this selected population.

Conclusion:

A strategy of empirical H. pylori eradication therapy can safely reduce the requirement for endoscopy in young dyspeptic patients without sinister symptoms.
Influence of clarithromycin dosage on pantoprazole combined triple therapy for eradication of Helicobacter pylori
Authors: Ellenrieder  , Fensterer  , Waurick  , Adler  , Glasbrenner
Published: March 2003

Background:

Low‐dose clarithromycin (250 mg b.d.) in combination with omeprazole and metronidazole has been recommended for the eradication of Helicobacter pylori. Whether the substitution of omeprazole by pantoprazole requires adjustment of the clarithromycin dose is not known.

Aim:

To directly compare the efficacy and tolerability of two different dosages of clarithromycin in combination with pantoprazole and metronidazole.

Methods:

One hundred and sixty‐three patients with endoscopically confirmed gastritis, gastric or duodenal ulcers and positive H. pylori findings in the rapid urease test were randomized and treated for 7 days with pantoprazole (40 mg b.d.), metronidazole (500 mg b.d.) and clarithromycin using either a regimen of 500 mg b.d. (group PMC 500) or 250 mg b.d. (group PMC 250). Eradication success was determined no less than 4 weeks after concluding therapy using the 13C‐urea breath test.

Results:

One‐hundred and thirty‐nine patients completed the study. Based on a per protocol analysis, successful eradication was documented in 63/70 patients (90.0%) in group PMC 500 and in 62/69 patients (89.9%) in group PMC 250. Based on the intention‐to‐treat analysis, eradication rates were 78.8% (group PMC 500) and 75.6% (group PMC 250). The incidence of adverse effects was significantly higher in patients receiving PMC 500 (50.0%) than in those receiving PMC 250 (25.4%).

Conclusions:

Triple therapy with pantoprazole, metronidazole and clarithromycin provides an efficient eradication regimen for H. pylori infection. A low dose of clarithromycin is equal to a higher dose in therapeutic efficacy and it offers the advantage of improved tolerance and lower cost.
One‐week use of ranitidine bismuth citrate, amoxycillin and clarithromycin for the treatment of Helicobacter pylori‐related duodenal ulcer
Authors: Sung  , Leung  , Ling  , Yung  , Chan  , Lee  , Cheng  , Chung
Published: March 2003

Background:

Proton pump inhibitors have been widely used in combination with amoxycillin, clarithromycin or metronidazole for the treatment of Helicobacter pylori infection.

Aim:

To study the effects of 1‐week ranitidine bismuth citrate (RBC)‐based triple therapy in the treatment of H. pylori‐related duodenal ulcers.

Method:

Patients with duodenal ulcers and H. pylori infection were prospectively randomized to receive either RBC with amoxycillin and clarithromycin for 1 week (RAC), or omeprazole with amoxycillin and clarithromycin for 1 week (OAC). No additional ulcer healing drug was used after the 1‐week medication. Patients were assessed for H. pylori eradication, ulcer healing and side‐effects after receiving the therapies.

Results:

One hundred consecutive patients were recruited to this study, with 50 patients randomized to each treatment group. In the intention‐to‐treat analysis, duodenal ulcers were completely healed in 45 (90%) patients in the RAC group and 43 (89.6%) in the OAC group (P = 1.0). H. pylori eradication was confirmed in 47 (94%) in the RAC group and 42 (87.5%) in the OAC group (P = 0.31). There was no significant difference in the severity of side‐effects experienced by the two treatment groups.

Conclusion:

One‐week RBC‐based triple therapy is an effective treatment for H. pylori‐related duodenal ulcers. The therapeutic effects are comparable to a 1‐week course of proton pump inhibitor‐based triple therapy.
The effect of cisapride on dyspepsia symptoms and the electrogastrogram in patients with non‐ulcer dyspepsia
Authors: Besherdas  , Leahy  , Mason  , Harbord  , Epstein
Published: March 2003

Background:

The electrogastrogram (EGG), which records gastric myoelectrical activity, is abnormal in one‐third of adult patients with non‐ulcer dyspepsia (NUD).

Aim:

To observe the effects of cisapride on EGG in adults with NUD.

Methods:

Twenty‐seven NUD patients who had undergone a pre‐ and post‐prandial EGG were entered into an open study. All patients completed a dyspepsia symptom questionnaire and were then treated with cisapride 10 mg t.d.s. The dyspepsia questionnaire was repeated in all those completing 4 weeks of treatment. Those with an initial abnormal EGG (< 70% of slow wave activity at 2–4 cycles per minute) had a repeat EGG at the end of the study.

Results:

Treatment with cisapride was associated with a significant improvement in the post‐prandial EGG (P = 0.007). After 4 weeks of treatment, 7 of 13 abnormal EGGs normalized. Symptom scores improved significantly in the 13 patients with an abnormal EGG who completed treatment (P < 0.0003), but not in NUD patients with a normal EGG (P = 0.48).

Conclusion:

In this open study, treatment of NUD with cisapride was associated with significant symptom improvement in patients with an abnormal pre‐treatment EGG, but not those with a normal EGG, with a significant improvement of the post‐prandial EGG.
Trends in prescribing H2‐receptor antagonists and proton pump inhibitors in primary care
Authors: Martin  , Lim  , Kerry  , Hilton
Published: March 2003

Background:

H2‐receptor antagonists and proton pump inhibitors account for approximately 15% of primary care prescribing costs in the UK.

Aim:

To examine the use of antisecretory drugs in primary care between October 1991 and September 1996.

Method:

Analysis of prescribing data from an ongoing postal survey performed every 3 months on a rolling quota of 250 UK general practitioners (GPs), identified from a representative sampling frame of 1000 GPs.

Results:

There were 8811 new courses of proton pump inhibitors and 11 948 new courses of H2‐receptor antagonists during this study. The number of new prescriptions for proton pump inhibitors increased by 174.5%, but decreased for H2‐receptor antagonists by 12.5%. Proton pump inhibitors were mostly prescribed for reflux disease (52.7%) and H2‐receptor antagonists for non‐specific dyspepsia (43.6%). Proton pump inhibitors (14.1%) were less likely to be stopped than H2‐receptor antagonists (35.3%) overall, and they were less likely to be stopped because of perceived ineffectiveness (5.3%) than H2‐receptor antagonists (23.8%). The rate of stopping treatment because of side‐effects was about 3% for both classes of drug.

Conclusions:

Prescribing of proton pump inhibitors has increased sharply each year since 1991. One reason may be that GPs perceive proton pump inhibitors to be more effective than H2‐receptor antagonists.
Evidence for impaired assimilation and increased colonic fermentation of protein, related to gastric acid suppression therapy
Authors: Evenepoel  , Claus  , Geypens  , Maes  , Hiele  , Rutgeerts  , Ghoos
Published: March 2003

Background:

Although the role of gastric digestion (by acid‐dependent pepsins) in overall protein assimilation has never thoroughly been studied, it is generally considered to be limited. Protein that escapes assimilation in the small intestine is intensely fermented by the colonic flora. Phenol and p‐cresol are specific bacterial metabolites of tyrosine.

Aim:

To elucidate the role of gastric digestion of protein by evaluating the influence of acid suppression therapy on overall protein assimilation and fermentation.

Methods:

Protein assimilation was studied in 16 healthy subjects under basal conditions and after omeprazole treatment using the combined 14C‐octanoic acid/13C‐egg white breath test. The degree of protein fermentation was estimated by measuring the urinary output of phenol and p‐cresol in 41 healthy volunteers and in 17 patients treated for more than 1 month with omeprazole because of peptic disease.

Results:

Protein assimilation was significantly impaired after omeprazole treatment. Gastric emptying, conversely, was not affected. The urinary output of phenol and p‐cresol was increased in patients treated with omeprazole as compared to untreated controls.

Conclusion:

Gastric acid suppression therapy hampers protein assimilation and may promote protein malabsorption. Gastric digestion is likely to play a substantial role in overall protein assimilation.
Effects of somatostatin on proximal gastric motor function and visceral perception
Authors: Mearadji  , Straathof  , Biemond  , Lamers  , Masclee
Published: March 2003

Background:

Somatostatin affects gastrointestinal motility and secretion and visceral sensation, but little is known about its effects on the proximal stomach.

Aim:

To evaluate the effects of somatostatin on proximal gastric motor function and perception of symptoms.

Methods:

Six healthy subjects participated in two experiments performed in random order during continuous intravenous infusion of saline or somatostatin (250 μg/h). Proximal gastric motor function was evaluated using a barostat. We performed pressure and volume distensions and a barostat procedure (minimal distending pressure + 2 mmHg). Symptoms were evaluated at regular intervals using visual analogue scales (VAS).

Results:

Neither minimal distending pressure nor gastric fundal tone were significantly different between somatostatin and saline. Pressure–volume curves during distensions were not influenced by somatostatin. However, phasic volume waves were significantly (P < 0.001) reduced by somatostatin, and somatostatin significantly (P < 0.05) reduced symptom perception of fullness and abdominal pressure during stepwise distensions.

Conclusions:

Continuous infusion of somatostatin does not influence gastric compliance but it inhibits phasic volume waves and significantly reduces visceral perception.
Soluble adhesion molecules correlate with liver inflammation and fibrosis in chronic hepatitis C treated with interferon‐α
Authors: Iacono  , García‐Monzón  , Almasio  , García‐Buey  , Craxí  , Moreno‐Otero
Published: March 2003

Background:

In chronic hepatitis C the relation of circulating adhesion molecules to disease features before, during and after therapy has not been completely established.

Aim:

To analyse the basal levels of circulating adhesins and the changes induced by interferon in these patients.

Methods:

We studied, using ELISA assays, the serum levels of soluble intercellular adhesion molecule‐1 (sICAM‐1) and vascular cell adhesion molecule‐1 (sVCAM‐1) in 52 patients with chronic hepatitis C on entry, prior to finalizing a 6‐month course of interferon‐α therapy and at the end of the follow‐up. Correlations with clinical, virological and histological features, including inflammation and fibrosis, were calculated by Pearson’s r‐test.

Results:

Liver necroinflammation was more closely related to sICAM‐1 (r = 0.54, P = 0.0000) than to sVCAM‐1 (r = 0.32, P = 0.02). Fibrosis, both as serum pIIIP and histological scoring, was, however, clearly related to sVCAM‐1 (1071 ± 291 in patients who scored 0–2 vs. 1870 ± 458 in patients who scored 3–4; P = 0.0000). Severe fibrosis was never found below a sVCAM‐1 cut‐off threshold of 1300 ng/mL. Levels of both adhesins did not correlate with viraemia and were comparable among 1b and non‐1b genotypes. Sustained response to interferon was significantly related to low viraemia (P = 0.03), non‐1b type (P = 0.04) and low sICAM‐1 (P = 0.04), but not to sVCAM‐1. On finalizing therapy, patients with normal transaminases had reduced sICAM‐1 (P = 0.0005), but not sVCAM‐1 levels.

Conclusions:

In chronic hepatitis C, sICAM‐1 was a marker of liver necroinflammation while sVCAM‐1 reflected fibrosis. Both low sVCAM‐1 and pIIIP serum concentrations were strictly linked, suggesting that measuring sVCAM‐1 could give information on the degree of liver fibroplasia.
Review article: rabeprazole’s profile in patients with gastrointestinal diseases
Authors: Humphries  , Barth
Published: March 2003

The selection of agents to treat patients with acid‐related gastrointestinal diseases requires knowledge of their efficacy, tolerability, and ease of dosing among individuals with differing disease severities and other baseline characteristics. The efficacy and favourable benefit–risk profile of rabeprazole, a new proton pump inhibitor, has been demonstrated in controlled clinical trials of patients with gastro‐oesophageal reflux disease (GERD), duodenal ulcers, and gastric ulcers.

In comparative trials, rabeprazole is at least as effective as omeprazole for the treatment of GERD, duodenal ulcers, and gastric ulcers, and it is superior to histamine2‐receptor antagonists for the treatment of GERD and duodenal ulcers. Its once‐daily dosing regimen and low potential for interaction with drugs metabolized by the cytochrome P450 system make it a particularly attractive option for the treatment of acid‐related diseases among older individuals.

Rabeprazole is likely to be a valuable new addition to its class in treating patients with acid‐related gastrointestinal diseases given its efficacy in acid suppression, high healing rates, rapid symptom relief, and convenient dosing.
Low‐dose lansoprazole provides greater relief of heartburn and epigastric pain than low‐dose omeprazole in patients with acid‐related dyspepsia
Authors: JONES  , CROUCH
Published: March 2003

Aim

: To compare the relative efficacies of lansoprazole 15 mg o.m. and omeprazole 10 mg o.m. in relieving heartburn and epigastric pain in patients with acid‐related dyspepsia. In addition, the study compared the safety profiles of the two treatments.

Methods

: This double‐blind, parallel group, randomised, multicentre study was conducted in 52 general practices in the UK. A total of 609 patients was recruited, 562 of whom were eligible for inclusion in the intention‐to‐treat analysis. All of the patients had experienced at least mild heartburn or mild epigastric pain persistently on at least 4 of the previous 7 days; patients with severe symptoms were excluded. 283 patients received lansoprazole 15 mg and 279 received omeprazole 10 mg, both for 4 weeks. The main efficacy measure was relief of symptoms, based on physician assessments.

Results

: In the intention‐to‐treat population, a complete relief of overall primary symptoms of dyspepsia was achieved after 2 weeks in 53% of patients receiving lansoprazole and in 41% of patients receiving omeprazole (P = 0.007). After 4 weeks, 59% of the lansoprazole group and 51% of the omeprazole group had achieved complete symptom relief (P = 0.078). Antacids were taken for additional relief of symptoms in fewer patients given lansoprazole compared to the omeprazole group in the third and fourth weeks (P = 0.035) and also significantly fewer antacids were taken by patients in the lansoprazole group compared with patients in the omeprazole group (P = 0.033). The proportion of patients reporting adverse events was similar in both groups.

Conclusion

: Low‐dose lansoprazole is more effective than low‐dose omeprazole in the treatment of patients with mild heartburn or epigastric pain in general practice.
Prescription of acid‐suppressing drugs in relation to endoscopic diagnosis: a record‐linkage study
Authors: PRACH  , MCGILCHRIST  , MURRAY  , JOHNSTON  , MACDONALD
Published: March 2003

Background

: Although widely used, few data are available on the appropriateness of prescribing of acid‐suppressing drugs (ASDs), despite guidelines on the investigation and treatment of dyspeptic patients.

Methods

: We created a database of 62 000 endoscopy examinations and record‐linked these to a prescribing database. Endoscopic diagnoses were classified into peptic, nonpeptic and others. The H2‐antagonists, omeprazole and misoprostol, were studied.

Results

: 35 000 patients had one or more endoscopies during 1978–93; two‐thirds were over 45 years of age at first endoscopy. A quarter of all patients who had been endoscoped had consistently normal examinations. Peptic oesophageal pathology was the commonest positive finding. A quarter of those prescribed ASDs between 1989 and 1993 had been endoscoped between 1978 and 1993. In those with a peptic diagnosis prescribed any ASD, the pathologies found were: oesophageal (42.9%), duodenal (36.3%) and gastro‐pyloric (21.3%). Patients prescribed omeprazole were more likely to have undergone endoscopy than those prescribed other ASDs, and they were also more likely to have peptic oesophageal pathology. Long‐term prescribing (>56 days per year) occurred in two‐thirds of patients prescribed ASDs and 40% had at least one endoscopy. In those prescribed short‐term ASDs, 20% had undergone at least one endoscopy. Peptic and nonpeptic endoscopic pathology was associated with increased ASD prescribing, but a normal endoscopy did not reduce prescribing.

Conclusion

: ASD prescribing appeared to be mainly symptom‐driven. Positive endoscopic findings increased the prescribing of ASDs, but normal findings did not reduce it.
The effect of curcumin and placebo on human gall‐bladder function: an ultrasound study
Authors: Rasyid  , Lelo
Published: March 2003

Background:

The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall‐bladder.

Aims:

To compare the effect of 20 mg curcumin or placebo on the gall‐bladder volume of healthy volunteers.

Methods:

A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall‐bladder volume. The data obtained was analysed by paired Student’s t‐test.

Results

The fasting gall‐bladder volumes of 15.74 ± 4.29 mL on curcumin and 15.98 ± 4.08 mL on placebo were similar (P > 0.20). The gall‐bladder volume was reduced within the period after curcumin administration. The percentage of gall‐bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 ± 6.9, 16.8 ± 7.4, 22.0 ± 8.5 and 29.3 ± 8.3%, respectively, which was statistically significant compared to placebo.

Conclusion:

On the basis of the present findings, it appears that curcumin induces contraction of the human gall‐bladder.
Serum gastrin and chromogranin A during medium‐ and long‐term acid suppressive therapy: a case‐control study
Authors: Sanduleanu  , Stridsberg  , Jonkers  , Hameeteman  , Biemond  , Lundqvist  , Lamers  , Stockbrügger
Published: March 2003

Background:

Serum chromogranin A (CgA) is regarded as a reliable marker of neuroendocrine proliferation. We previously described increased serum CgA levels during short‐term profound gastric acid inhibition.

Aim:

To investigate serum gastrin and CgA levels in dyspeptic patients during continuous medium‐ (6 weeks to 1 year), or long‐term (1–8 years) gastric acid suppressive therapy.

Patients and methods:

114 consecutive dyspeptic patients referred for upper gastrointestinal endoscopy were enrolled in a cross‐sectional, case‐control study [62 patients on continuous antisecretory therapy, either with proton pump inhibitors (n = 47) or H2‐receptor antagonists (H2RA) (n = 15) for gastro‐oesophageal reflux disease with or without Barrett’s oesophagus or functional dyspepsia, and 52 age‐ and sex‐matched patients without medical acid inhibition and with normal endoscopic findings (control group)]. Omeprazole doses ranged from 20 mg to 80 mg daily and ranitidine from 150 mg to 450 mg daily. Fasting serum CgA and serum gastrin levels were measured by radioimmunoassay (reference values: serum CgA < 4.0 nmol/L; serum gastrin < 85 ng/L).

Results:

Fasting serum CgA levels positively correlated with serum gastrin in the entire study population (r = 0.55, P = 0.0001). Median serum CgA values were higher in patients treated with a proton pump inhibitor than H2RA [2.8 (2.0–5.9) nmol/L vs. 2 (1.9–2.3) nmol/L, P < 0.002] and controls [2.8 (2.0–5.9) nmol/L vs. 1.8 (1.5–2.2) nmol/L, P < 0.0001) and did not differ between patients treated with H2RA or controls. Serum gastrin and CgA levels in patients on proton pump inhibitor therapy positively correlated with the degree and duration of acid inhibition. Patients on long‐term proton pump inhibitor therapy had significantly higher fasting serum gastrin and CgA than those on medium‐term proton pump inhibitor therapy [127 (73–217) ng/L vs. 49 (29–78) ng/L, P < 0.0001 and 4.8 (2.8–8) ng/L vs. 2.1 (1.9–2.6) ng/L, P < 0.001]. No such relation was found in patients on medium‐ vs. long‐term H2RA. Overall, patients with positive Helicobacter pylori serology had higher serum gastrin and CgA levels than those with negative H. pylori serology [51 (27–119) ng/L vs. 27 (14–79) ng/L, P = 0.01, 2.4 (1.9–3.4) nmol/L vs. 2.0 (1.7–2.5) nmol/L, P = 0.05].

Conclusions:

During long‐term continuous proton pump inhibitor treatment, serum gastrin and CgA levels are significantly elevated compared to H2RA treatment and nontreated dyspeptic controls. H. pylori infection seems to affect gastric ECL cell secretory function. Increased serum CgA values during long‐term profound gastric acid inhibition could reflect either gastric enterochromaffin‐like cell hyperfunction or proliferative changes.
Effects of octreotide treatment on early TNF‐α production and localization in experimental chronic colitis
Authors: LAMRANI  , TULLIEZ  , CHAUVELOT‐MOACHON L , CHAUSSADE  , MAUPRIVEZ  , HAGNÉRÉ  , VIDON
Published: March 2003

Background

: Colitis induced by trinitrobenzene sulphonic acid (TNB) is a model of Th1 disease, mainly explored from the third day of induction. It has recently been shown that octreotide and other somatostatin analogues can modify inflammatory/immune processes by acting on cytokines.

Aim

: To examine TNFα production and the effect of preventive treatment with octreotide, during the early phase of TNB‐colitis.

Methods

: Thirty milligrams TNB with 50% ethanol was instilled into the colon of male Wistar rats. Treated groups received octreotide (2 × 10 μg.day/rat) or dexamethasone (1 × 2 mg.day/kg), subcutaneously, with the first injection before TNB. Eight and 80 h later, the colon was excised and processed for histology, TNFα immunohistochemistry, quantification of cytokine release ex vivo and tissue‐inducible NO synthase (iNOS) activity.

Results

: Maximal TNFα production was observed at the 8th hour, associated with intense immunostaining of the external muscle layer. Octreotide treatment decreased TNFα expression (staining and activity) and iNOS activity. At the 80th hour, submucosal macrophages were positive for TNFα and colonic production of IL1β and interferon γ was increased; all these effects were reduced by octreotide treatment.

Conclusions

: TNFα was expressed early by resident muscle cells, before staining of infiltrated immune cells and increased production of interferon γ. TNFα regulation by octreotide suggests that this drug might exert anti‐inflammatory properties via smooth muscle cells.
The effect of cisapride on duodenal acid exposure in the proximal duodenum in healthy subjects
Authors: VERHAGEN  , ROELOFS  , EDELBROEK  , SMOUT  , AKKERMANS
Published: March 2003

Aim

: To investigate the effect of the prokinetic drug, cisapride, on fasting and postprandial acid exposure in the proximal duodenum.

Methods

: Using a double‐blind, placebo‐controlled crossover study design, 12 healthy male volunteers were studied. After 1 week of dosing (cisapride 20 mg b.d. orally or placebo), fasting and postprandial antroduodenal pH‐and pressure‐recordings were made. Using a small‐caliber (4 mm) catheter, containing one antral and two duodenal pH electrodes, and two antral and three duodenal pressure recording sites. Transmucosal potential difference was measured to ensure proper catheter position. Infusions of 0.1 N HCl were given in the duodenal bulb.

Results

: Endogenous acidification of the duodenal bulb occurred more frequently during phase II and post‐ prandially, compared to phase I (P < 0.001). During phase I, alkalinization of the antrum was observed. Cisapride significantly increased the postprandial number of duodenal acidic periods (P < 0.02), but shortened their duration (P < 0.04). The duodenal motor response elicited by exogenous acid was lower during phase I (P < 0.05).

Conclusions

: Antral and proximal duodenal acidity vary with the phases of the interdigestive motor complex. Cisapride shortens the individual periods of duodenal acidification.
Specific inhibition of cyclooxygenase‐2 with MK‐0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen
Authors: Lanza F. L. , Rack M. F. , Simon T. J. , Quan H. , Bolognese J. A. , Hoover M. E. , Wilson F. R. , Harper S. E.
Published: March 2003

Background

: Compared with currently available NSAIDs (which inhibit COX‐1 and COX‐2 isoforms of cyclooxy‐ genase), MK‐0966 (a specific COX‐2 inhibitor) is expected to cause less gastrointestinal toxicity.

Aim

: To compare the effect on the upper gastrointestinal mucosae of a high dose of MK‐0966 with that of conventional doses of ibuprofen and aspirin.

Methods

Healthy subjects (n = 170; age range 18–54 years) with endoscopically normal gastric and duodenal mucosa were randomized to either MK‐0966 250 mg q.d. (n = 51), ibuprofen 800 mg t.d.s. (n = 51), aspirin 650 mg q.d.s. (n = 17), or placebo (n = 51) in this 7‐day, double‐blind, parallel‐group study. The mucosae were evaluated by endoscopy using a predefined scale; scores could range from 0 to 4. The primary end‐point was the percentage of subjects who developed a mucosal score ≥ 2 (i.e. the development of one or more erosions). To evaluate COX‐1 activity, serum thromboxane B2 levels were determined in a subset of the population.

Results

The percentage of subjects who developed a mucosal score ≥ 2 in the MK‐0966 group (12%) was significantly lower (P < 0.001) than that in the ibuprofen (71%) and aspirin (94%) groups, and was similar to that in the placebo group (8%). Only ibuprofen and aspirin significantly (P < 0.0001) reduced baseline thromboxane B2 levels. All treatments were generally well tolerated.

Conclusions

In this acute short‐term endoscopic study, MK‐0966 250 mg q.d. (a dose at least 10 times higher than that demonstrated to reduce the signs and symptoms of osteoarthritis) produced significantly less gastrointestinal mucosal damage than either ibuprofen 800 mg t.d.s. or aspirin 650 mg q.d.s. and was comparable to placebo in this regard.
A new quadruple therapy for Helicobacter pylori: influence of resistant strains on treatment outcome
Authors: Okada M. , Nishimura H. , Kawashima M. , Okabe N. , Maeda K. , Seo M. , Ohkuma K. , Takata T.
Published: March 2003

Background

: There have been no reports concerning the efficacy and safety of a 1‐week quadruple therapy regimen of omeprazole, amoxycillin, roxithromycin and metronidazole for Helicobacter pylori infections and the impact of primary resistance on the eradication rate.

Methods

: One hundred and sixty‐nine consecutive patients with peptic ulcer disease as well as gastritis with biopsy‐proven H. pylori infection were entered into an open study of omeprazole 20 mg o.m., amoxycillin 500 mg t.d.s., roxithromycin 150 mg b.d., and metronidazole 250 mg t.d.s. Helicobacter pylori status was determined by urease test, histology and culture. Susceptibility to amoxycillin, metronidazole and roxithromycin was determined by the E‐test.

Results

: H. pylori was eradicated in 155 out of 169 (92%; 95% CI 88–96%) by intention‐to‐treat analysis, and in 155 out of 163 (95%; 95% CI 92–98%) by per protocol analysis. The prevalence of primary resistance against amoxycillin, roxithromycin and metronidazole was 2 out of 166 (1%), 16 out of 166 (10%) and 27 out of 166 (16%), respectively. H. pylori was eradicated in 25 out of 27 (93%) patients with metronidazole‐resistant strains compared with 130 out of 136 (96%) in patients with metronidazole‐sensitive strains of H. pylori. It was eradicated in 15 out of 16 (94%) patients with roxithromycin‐resistant strains while in 140 out of 147 (95%) patients with roxithromycin‐sensitive strains of H. pylori, and in two out of two (100%) patients with amoxycillin‐resistant stains compared with 153 out of 161 (95%) in patients with amoxycillin‐sensitive strains. H. pylori was eradicated in three out of four (75%) patients with double resistance against metronidazole and roxithromycin compared with 152 out of 159 (96%) patients with sensitive strains to metronidazole and or roxithromycin. None of these differences were statistically significant. Severe side‐effects were found in only one out of 169 patients—anaphylaxis due to penicillin.

Conclusions

: The 1‐week quadruple therapy with omeprazole, amoxycillin, metronidazole and roxithromycin was found to eradicate H. pylori in over 90% of all patients. This regimen was also found to be beneficial for patients with pre‐treatment resistant strains to metronidazole, roxithromycin or amoxycillin, and was observed to be safe and well‐tolerated.
The effect of omeprazole on gastro‐oesophageal reflux and symptoms during strenuous exercise
Authors: Peters  , De Kort A. F. C. C. , Van Krevelen H. , Akkermans  , Van Berge Henegouwen G. P. , Bol  , Mosterd  , De Vries W. R.
Published: March 2003

Background

: Strenuous exercise exacerbates gastro‐oesophageal reflux and symptoms and this may be diminished by antisecretory medication with omeprazole.

Methods

: Fourteen well‐trained athletes (13 men, one woman), who indicated suffering from either heartburn, regurgitation or chest pain during competition running, performed two experimental trials at 2‐week intervals using a randomized, double‐blind, placebo‐controlled crossover design. During the 6 days preceding the trial and on the trial day itself either 20 mg of omeprazole or a placebo was administered. Two hours after a low‐fat breakfast and 1 h after the last study dose, the trial started with five successive 50‐min periods: rest, three running periods on a treadmill, and recovery. Reflux (percentage time and number of periods oesophageal pH < 4) was measured with an ambulant pH system during these periods.

Results

: Compared to rest, reflux lasted significantly longer and occurred more frequently during the first running period, irrespective of the intervention, whereas during the second running period this effect was only observed with the placebo. Reflux occurred for longer and more frequently with the placebo than with omeprazole, but this was significant during the first two running periods only. Seven subjects reported heartburn, regurgitation and/or chest pain during exercise, irrespective of the intervention. Only a minority of the symptom periods was actually associated with acid reflux and in all cases this concerned periods with heartburn.

Conclusions

: Running‐induced acid reflux, but not symptoms, were decreased by omeprazole, probably because most symptoms were not related to acid reflux.
Effect of ursodeoxycholic acid administration in patients with acute viral hepatitis: a pilot study
Authors: Fabris  , Tositti  , Mazzella  , Zanetti  , Nicolin  , Pellizzer  , Benedetti  , De Lalla F.
Published: March 2003

Background

: Ursodeoxycholic acid (UDCA) is able to improve biochemical markers of cholestasis, with a parallel decrease in transaminases, in various cholestatic liver diseases.

Aim

: To evaluate the effects of UDCA administration on acute viral hepatitis‐related cholestasis and the course of acute viral hepatitis.

Methods

: Seventy‐nine consecutive patients with acute viral hepatitis (HBV: 43, HCV: 11, HAV: 15, HEV: 3, Non A‐E: 7) were randomized to receive either UDCA for 3 weeks or no treatment. Liver biochemistry and serum bile acid determinations were run at weekly intervals.

Results

: No significant differences were observed in mean percentage decreases in transaminases between treated and untreated patients. By contrast, cholestatic indexes decreased significantly more quickly in patients treated with UDCA than in controls, and this effect was more evident in patients with increasing alanine transaminase levels at admission. After a peak at the end of the first week of therapy, serum levels of conjugated ursodeoxycholic acid (CUDCA) showed a gradual decrease. Conjugated cholic acid (CCA) and chenodeoxycholic acid (CCDCA) showed a progressive decrease with the resolution of viral hepatitis, but no influence of UDCA administration was observed.

Conclusions

: Our study demonstrates that UDCA significantly improves cholestatic indices in patients with acute viral hepatitis, but this effect does not seem to affect the course of the illness.
Regression of columnar‐lined (Barrett’s) oesophagus with omeprazole 40 mg daily: results of 5 years of continuous therapy
Authors: Wilkinson  , Biddlestone  , Gore  , Shepherd
Published: March 2003

Background

: We have previously reported the effect of 2 years of omeprazole 40 mg daily on columnar‐lined (Barrett’s) oesophagus (CLO).

Aims

: In the present study, follow‐up has been extended to 5 years to assess the macroscopic and microscopic effects of continuing therapy.

Patients and methods

: The 23 patients have been followed for up to a further 3 years. Endoscopy with multiple biopsies was performed at the end of years 3, 4 and 5.

Results

: Although there had been a statistically significant regression in the length of CLO after 2 years, there was no overall further measurable change after 5 years. However, one patient showed complete macroscopic and microscopic regression. The number and size of macroscopic squamous islands within the CLO continued to increase, and there was a further increase in microscopic squamous re‐epithelialization of surface mucosa, gland ducts and Barrett’s gland tissue. Low‐grade dysplasia was found consistently in one patient in biopsies taken up to the end of year 3 but it could not be detected thereafter.

Conclusions

: Omeprazole 40 mg daily appears to have beneficial effects on CLO, although it rarely induces a complete regression. Whether the benefits will reduce the risk of malignant transformation is unknown.
The effect of dosing with omeprazole on the accuracy of the 13C‐urea breath test in Helicobacter pylori‐infected subjects
Authors: Connor  , Seow  , Ngu  , Katelaris
Published: March 2003

Background

: The 13C‐urea breath test (13C‐UBT) is an accurate means of Helicobacter pylori diagnosis. However, proton pump inhibitors may suppress H. pylori and cause false negative results.

Aim

: To study the kinetics of H. pylori suppression by omeprazole during and after short‐term use.

Methods

: Volunteers underwent a baseline 13C‐UBT (13C‐urea 100 mg). H. pylori‐positive subjects took omeprazole 20 mg daily for 14 days. Those who remained 13C‐UBT positive (δ13CO2 ≥ 5) continued omeprazole for a further 14 days. 13C‐UBTs were performed weekly on omeprazole and then every second day after it was stopped. False negatives occurred when δ13CO2 fell to < 5.

Results

: In 25 H. pylori‐positive subjects (mean age 43.9 ± 2.4 years; 21 females, 4 males) the mean baseline δ13CO2 was 28.1 ± 3.4. False negative breath tests occurred in three subjects after 7 days of omeprazole and in a further four subjects after 14 days. A further six subjects developed negative tests between Days 14 and 28. Following cessation of omeprazole, the 13C‐UBT became positive again in 12/13 subjects within 4 days and in all within 6 days, with a mean recovery to 99.9 ± 18.6% of baseline δ13CO2.

Conclusions

: False negative 13C‐UBTs are common during treatment with omeprazole and occur after as little as 7 days. Return to positive test results is rapid after cessation of omeprazole. These findings are relevant to the timing of testing in clinical practice.
Ibuprofen augments gastrointestinal symptoms in lactose maldigesters during a lactose tolerance test
Authors: Peuhkuri  , Nevala  , Vapaatalo  , Moilanen  , Korpela
Published: March 2003

Background

: Clinical symptoms during lactose tolerance test mimic those seen after therapeutic administration of prostaglandins, and resemble inflammatory processes.

Aim

: To investigate the possibility that lactose‐induced gastrointestinal symptoms are associated with prostaglandins and/or nitric oxide.

Methods

: After an overnight fast, nine maldigesters ingested lactose or sucrose with or without an inhibitor of prostaglandin synthesis (ibuprofen), in a randomised double‐blind crossover trial. Gastrointestinal symptoms, concentrations of PGE2‐M in blood and urine, and urinary 6‐keto PGF1α (as indicators of prostaglandin synthesis), and urinary nitrate and nitrite as well as cyclic GMP excretions (as indicators of nitric oxide formation), were measured.

Results

: Ibuprofen increased the first 3‐h symptom scores (flatulence + borborygmi + abdominal bloating + pain) caused by lactose (P=0.008) but not sucrose. The concentrations of PGE2‐M in the plasma and in the urine were unaffected. Lactose increased the urinary excretion of 6‐keto PGF1α by about 30% (P=0.17), which was inhibited by ibuprofen (P=0.02). The production of nitric oxide was unaffected by lactose or ibuprofen.

Conclusion

: The inhibition of prostaglandin synthesis intensified gastrointestinal symptoms in lactose maldigesters, suggesting a negligible role for prostanoids in lactose‐induced symptoms.
5‐HT4 receptor antagonism in irritable bowel syndrome: effect of SB‐207266‐A on rectal sensitivity and small bowel transit
Authors: Houghton  , Jackson  , Whorwell  , Cooper
Published: March 2003

Background

: Pre‐clinical studies indicate that the 5‐hydroxytryptamine (5‐HT)4 receptor may be involved in the pathophysiology of irritable bowel syndrome and that antagonism of this receptor may be an effective therapeutic strategy.

Aim

: To investigate the effects of SB‐207266‐A, a selective 5‐HT4 receptor antagonist on rectal sensitivity and small bowel transit in patients with irritable bowel syndrome.

Methods

: Eighteen patients with diarrhoea‐predominant irritable bowel syndrome and a history of increased rectal sensitivity were randomized to receive either SB‐207266‐A (20 mg) or placebo for 10 days. Following a washout period, patients were then crossed over to receive the alternative therapy for 10 days. Rectal sensitivity and orocaecal transit time were assessed on day 10 of each treatment period. In addition, patients were asked whether they had experienced any changes in their symptoms.

Results

: Fifteen patients completed the study. SB‐207266‐A significantly increased orocaecal transit time towards normal (placebo: 5.3 h (4.0–7.2 h), mean (IQR) vs. SB‐207266‐A: 6.5 h (4.8–8.0 h); P=0.027) and tended to decrease rectal sensitivity (volume to discomfort 89 mL (60–150 mL), geometric mean (IQR) vs. 107 mL (75–150 mL); P=0.134). Eleven out of 15 patients reported symptomatic improvements with SB‐207266‐A but none with placebo. SB‐207266‐A was well tolerated.

Conclusion

: Our results support a role for the 5‐HT4 receptor in the pathophysiology of irritable bowel syndrome and suggest that the selective 5‐HT4 antagonist, SB‐207266‐A, is worthy of further evaluation in this disorder.