bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of age on the steady state disposition of drugs commonly used for the eradication of Helicobacter pylori
Authors: Ammon  , Treiber  , Kees  , Klotz
Published: March 2003

Background:

The success of eradication therapy for Helicobacter pylori might be affected by the age of patients.

Aim:

To investigate whether disposition of drugs commonly used for H. pylori eradication is age‐dependent.

Methods:

Trough steady state serum levels of lansoprazole or ranitidine, amoxycillin, clarithromycin and metronidazole were monitored in 232 patients during the last dosing interval of a 5‐day quadruple H. pylori eradication regimen. Detailed pharmacokinetic analysis was performed in 28 patients.

Results:

Linear correlations between age and trough serum levels were observed with lansoprazole (r=0.25; P=0.002), ranitidine (r=0.38; P=0.001) and clarithromycin (r=0.36; P < 0.0001). These associations were also inversely dependent of creatinine clearance for ranitidine (r=0.36; P=0.001) and clarithromycin (r=0.30; P < 0.0001). Multiple linear regression revealed age as an important factor influencing trough serum levels of lansoprazole, clarithromycin and ranitidine. There were significant inverse relationships between creatinine clearance and area under curve of ranitidine (r=0.88; P < 0.0001) and amoxycillin (r=0.56; P=0.002). Multiple linear regression revealed serum creatinine as the most important factor influencing the area under curve of ranitidine, clarithromycin and amoxycillin.

Conclusions:

Age per se has little influence on pharmacokinetics of amoxycillin and ranitidine, which depend more on age‐dependent decline in renal function. The influence of age, but not renal function was established for lansoprazole. Age and renal function have independent impacts on clarithromycin disposition.
Cerebral near infrared spectroscopy for the measurement of indocyanine green elimination in cirrhosis
Authors: Therapondos  , Plevris  , Stanley  , Peters  , Teig  , Hayes
Published: March 2003

Background:

Indocyanine green (ICG) clearance is a useful indicator of hepatic function but most measurement methods are invasive.

Aim:

To validate a less invasive technique using cerebral near infrared spectrophotometry (NIRS) to measure ICG elimination, and to compare it with the established methods for the determination of ICG clearance in a group of normal controls and patients with cirrhosis.

Method:

NIRS was used to measure ICG elimination in 41 cirrhotic patients and nine healthy volunteers. The first 13 of the cirrhotic patients also had their ICG clearance measured by the conventional spectrophotometric technique.

Results:

NIRS ICG elimination rate (ICG‐k) and spectrophotometry ICG‐k values correlated strongly (r= 0.828, P < 0.001, n=13). There was a significant reduction in the mean NIRS‐k in cirrhotic patients and within Child–Pugh classes A, B, and C (P < 0.001).

Conclusion:

Measurement of ICG elimination by the NIRS method is at least as reliable as the conventional spectrophotometric technique in normals and in patients with cirrhosis. This technique merits further development for use as a bedside, less invasive liver function test.
Efficacy of sucralfate for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole‐based regimen
Authors: Adachi  , Ishihara  , Hashimoto  , Hirakawa  , Niigaki  , Takashima  , Kaji  , Kawamura  , Sato  , Okuyama  , Watanabe  , Kinoshita
Published: March 2003

Background:

Sucralfate has an inhibitory action against Helicobacter pylori and enhances the anti‐H. pylori activity of antimicrobials.

Aim:

To evaluate the efficacy and safety of sucralfate‐based eradication therapy for H. pylori infection, compared with that based on lansoprazole, in a randomized multicentre study.

Subjects and methods:

The subjects were 150 H. pylori‐positive patients. They were randomly assigned to one of two regimens for 2 weeks: sucralfate 1 g t.d.s., amoxycillin 500 mg t.d.s., and clarithromycin 400 mg b.d. (SAC regimen: 75 patients); or lansoprazole 30 mg o.m. with the same antimicrobial medications (LAC regimen: 75 patients). Cure of infection was assessed by a 13C urea breath test 1 month after completion of treatment.

Results:

Eight patients (four in the SAC group and four in LAC group) could not continue therapy because of severe diarrhoea, and three did not take the 13C urea breath test after therapy. Cure rates for intention‐to‐treat, all‐patients‐treated, and per protocol analysis in the SAC group were 80%, 83%, and 88%, respectively, and those in the LAC group were 87%, 87%, and 92%, respectively. There were no significant differences in cure rate or adverse effects between the two regimens.

Conclusion:

Sucralfate in combination with amoxycillin and clarithromycin is as effective as lansoprazole‐based eradication therapy for H. pylori.
Rabeprazole, amoxycillin and low‐ or high‐dose clarithromycin for cure of Helicobacter pylori infection
Authors: Kihira K. , Satoh K. , Saifuku K. , Kawakami S. , Fukazawa K. , Ishino Y. , Kimura K. , Sugano K.
Published: March 2003

Background:

Rabeprazole sodium is a proton pump inhibitor.

Aim:

To evaluate the efficacy and safety of 1‐week triple therapy with rabeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori.

Methods:

A total of 100 subjects with H. pylori were randomly divided into two groups of 1‐week triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b.d. (RAC800, n=50). Endoscopic examination with four biopsies (two specimens from the antrum and two from the gastric body) was performed. The status of H. pylori infection was determined using culture and histology (Giemsa stain) of the biopsy specimens. Sensitivity to clarithromycin was determined using the E‐test: MIC > 8 g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be sensitive. Cure was defined as no evidence of H. pylori infection 1 month after completion of treatment.

Results:

There were no significant differences in the clinical characteristics of the two groups. Eradication rates (intention‐to‐treat and per protocol, respectively) were: RAC400: 86% (95% CI: 76–95%) and 89% (95% CI: 80–97%); RAC800: 94% (95% CI: 87–100%) and 97% (95% CI: 94–100%). There was no significant difference between the eradication rates of either regimen. Three subjects with failed eradication in the RAC400 group were all infected with a clarithromycin‐resistant strain before beginning the therapy. Haemorrhagic colitis was the only severe adverse event, which was observed in one patient in the RAC800 group.

Conclusion:

One‐week triple therapy with rabeprazole, amoxycillin and low‐dose clarithromycin is effective for the eradication of H. pylori infection.
Enhanced bioavailability of azathioprine compared to 6‐mercaptopurine therapy in inflammatory bowel disease: correlation with treatment efficacy
Authors: Cuffari C. , Hunt S. , Bayless T. M.
Published: March 2003

Background:

Azathioprine and 6‐mercaptopurine have proven efficacy in the treatment of Crohn’s disease. Immunosuppression is mediated by their intracellular metabolism into active 6‐thioguanine metabolites, and clinical responsiveness to therapy in patients with inflammatory bowel disease has been correlated with the measure of erythrocyte 6‐thioguanine levels.

Aims and methods:

To perform a dosing equivalency analysis and comparison of clinical efficacy in 82 patients with inflammatory bowel disease on long‐term (> 2 months) therapy with either branded azathioprine (Imuran) (n=26), generic azathioprine (n=38), or 6‐mercaptopurine (n=18), based on the measurement of erythrocyte 6‐thioguanine metabolite levels.

Results:

Disease remission was achieved in 51% (42 out of 82) of patients treated with either azathioprine or 6‐mercaptopurine therapy, and correlated well with high erythrocyte 6‐thioguanine levels (> 250 pmoles/8 × 108 RBCs). Patients treated with either branded azathioprine or 6‐mercaptopurine achieved significantly higher erythrocyte 6‐thioguanine levels than patients treated with generic azathioprine, thereby suggesting that branded azathioprine has improved oral bioavailability compared to generic azathioprine. These data are consistent with the putative immunosuppressive role of 6‐thioguanine metabolites in the treatment of inflammatory bowel disease, and provides a basis for developing a therapeutic index of clinical efficacy based on the measurement of erythrocyte 6‐thioguanine metabolite levels.

Conclusions:

Our results suggest that differences in bioavailability may have clinical relevance when considering the need to optimize erythrocyte 6‐thioguanine metabolite levels in patients deemed unresponsive to treatment on conventional drug dosages.
Helicobacter pylori–gastrin link in MALT lymphoma
Authors: Konturek P. C. , Konturek S. J. , Starzyska T. , Marlicz K. , Bielanski W. , Pierzchalski P. , Karczewska E. , Hartwich A. , Rembiasz K. , Lawniczak M. , Ziemniak W. , Hahn E. C.
Published: March 2003

Background:

There is accumulating evidence for the role of Helicobacter pylori in the development of gastric cancer as well as of lymphomas that arise in mucosa‐associated lymphoid tissue (MALT). We reported recently that gastric cancer patients show high prevalence of cagA‐positive H. pylori and express gastrin and gastrin receptors enabling them to stimulate tumour growth in autocrine fashion.

Aims:

Since the H. pylori infection is considered to be more strongly associated with MALT lymphoma than with gastric cancer, we decided to determine the gastrin and its receptors’ mRNA expression and gastrin content in this tumour as well as the release of this hormone both into plasma and gastric lumen. Twenty MALT lymphoma patients were compared with 100 age‐ and gender‐matched controls with similar dyspeptic symptoms.

Results:

The overall H. pylori seropositivity in MALT lymphoma was about 90% and CagA positivity was 70%, compared to 56% and 33%, respectively, in controls. The serum gastrin in MALT lymphoma was about sixfold higher than in controls while gastric luminal gastrin in these patients was over 70 times higher than in controls. Gastrin content in tumour was about 10‐fold higher than in antral mucosa. Gastrin and gastrin‐receptor (CCKB‐receptor) mRNA were detected by reverse transcriptase–polymerase chain reaction in cancer tissue whilst in the fundic and antral mucosa, only enhanced expression of CCKB‐receptor mRNA and gastrin mRNA was detected, respectively. Histamine stimulation in MALT lymphoma induced acid secretion that was only about 30% of control value due to atrophic gastritis. This study confirms an important role of CagA‐positive H. pylori in the pathogenesis of MALT lymphoma and shows that this lymphoma is capable of synthesizing and releasing potent growth promoting gastrin, possibly due to the action on G‐cells of H. pylori‐originated Nα‐methyl histamine and cytokines (tumour necrosis factor alpha and interleukin‐8).

Conclusions:

Gastric MALT lymphoma is closely linked to CagA‐positive H. pylori infection. Gastrin and its receptors may be implicated in the pathogenesis of gastric lymphoma.
Omeprazole and CYP2C19 polymorphism: effects of long‐term treatment on gastrin, pepsinogen I, and chromogranin A in patients with acid related disorders
Authors: Sagar M. , Bertilsson L. , Stridsberg M. , Kjellin A. , Mårdh S. , Seensalu R.
Published: March 2003

Background:

The polymorphic enzyme CYP2C19 is of importance for the metabolism and effects of omeprazole during short‐term treatment.

Aim:

To investigate the relationship between CYP2C19 genotype and the effects of long‐term omeprazole treatment.

Material and methods:

A total of 180 patients with acid related disorders were genotyped for wild type and mutated CYP2C19 alleles by allele‐specific PCR amplification. Gastrin and chromogranin A were assessed by radioimmunoassays, and pepsinogen I and H. pylori serology were assessed by ELISA methods.

Results:

In 108 of the patients, who received a single dose of 20 mg omeprazole, there was no difference in gastrin and chromogranin A concentrations between the three CYP2C19 genotypes. In 72 patients on long‐term treatment (> 1 year) with 20 mg omeprazole daily, serum gastrin as well as plasma chromogranin A concentrations (mean ± s.e.) were both about threefold higher in the wild type/mutated (52.1 ± 7.6 p
M and 7.3 ± 1.3 n
M (n=19), respectively) compared to wild type/wild type (14.7 ± 0.9 p
M and 2.5 ± 0.1 n
M (n=52), respectively; both comparisons P=0.0001). In a single mutated/mutated patient on long‐term treatment, both gastrin and chromogranin A were high (88 p
M and 13.7 n
M, respectively). Serum pepsinogen I concentration was significantly lower in wild type/mutated (n=19) patients on long‐term treatment, compared with the corresponding wild type/wild type (n=49) group (147 ± 19 μg/L vs. 193 ± 12 μg/L, P=0.04).

Conclusion:

Patients with one (and probably also with two) mutated CYP2C19 allele(s) on long‐term treatment with omeprazole had significantly affected serum gastrin and pepsinogen I and plasma chromogranin A concentrations compared with patients with two normal alleles. This indicates that changes in gastric mucosal morphology during omeprazole treatment might be dependent upon the degree of the individual’s capacity to metabolize omeprazole.
Management of Helicobacter pylori in duodenal ulcer: a cost‐effectiveness analysis
Authors: García‐Altés A. , Jovell A. J. , Serra‐Prat M. , Aymerich M.
Published: March 2003

Background:

Empirical eradication therapy of H. pylori has been proposed as a therapeutic alternative for duodenal ulcer.

Aim:

To identify the cost‐effectiveness of empirical eradication therapy vs. test‐and‐treatment for the management of patients already diagnosed with a duodenal ulcer.

Methods:

A decision analysis was performed to compare the cost‐effectiveness of empirical eradication therapy of H. pylori diagnosed duodenal ulcer vs. eradication therapy after confirmatory diagnosis of Helicobacter pylori infection by means of several diagnostic tests.

Results:

The empirical eradication therapy of duodenal ulcer was found to be the most effective and cost‐effective strategy of all the alternatives. Amongst the alternatives, which included the previous performance of confirmatory diagnostic tests, the best cost‐effectiveness ratio used a serology test. The model was robust in the face of changes in the values of therapeutic effectiveness, sensitivity and specificity of the diagnostic tests, prevalence of H. pylori infection in duodenal ulcer, duration of the antisecretory therapy, and number of medical visits.

Conclusions:

Based on our cost‐effectiveness analysis, a treat approach is more effective and cost‐effective than a test‐and‐treat approach in the clinical management of already diagnosed duodenal ulcer.
5‐day vs. 7‐day triple therapy with rabeprazole, clarithromycin and amoxicillin for Helicobacter pylori eradication
Authors: Isomoto H. , Furusu H. , Morikawa T. , Mizuta Y. , Nishiyama T. , Omagari K. , Murase K. , Inoue K. , Murata I. , Kohno S.
Published: March 2003

Aim:

To determine whether a 5‐day regimen with rabeprazole, clarithromycin and amoxicillin (RCA) was as effective as a 7‐day regimen.

Methods:

A total of 139 H. pylori‐infected patients were randomized to receive either a 5‐day or 7‐day course of rabeprazole 10 mg b.d., clarithromycin 400 mg b.d. and amoxicillin 750 mg b.d. Eradication was assessed by CLO test, histology and 13C‐urea breath test.

Results:

On the intention‐to‐treat basis, eradication rates were 66% (46 out of 70) and 84% (58 out of 69) for the 5‐ and 7‐day regimens, respectively (P < 0.05). Using per protocol analysis, eradication rates were 70% (46 out of 66) and 91% (58 out of 64) for the 5‐ and 7‐day regimens, respectively (P < 0.01). Adverse events, which were observed in 14 patients from each group, caused discontinuation of treatment in only two patients, resulting in excellent compliance.

Conclusions:

Our 5‐day regimen of RCA yielded inferior results, whereas the 7‐day regimen achieved an eradication rate exceeding 90% on the per protocol basis. Therefore, treatment regimens of less than 7 days for proton pump inhibitor–clarithromycin–amoxicillin therapies cannot be recommended.
The effects of water extracts of CagA positive or negative Helicobacter pylori on proliferation, apoptosis and connexin formation in acetic acid‐induced gastric ulcer of rats
Authors: Mine T. , Endo C. , Kushima R. , Kushima W. , Kobayashi I. , Muraoka H. , Taki R. , Fujita T.
Published: March 2003

Aim: To investigate the influence of water extracts of CagA‐positive or ‐negative Helicobacter pylori on healing of chronic gastric ulcers and on connexin formation, proliferation and apoptosis, in acetic acid‐induced chronic gastric ulcers in rats.

Methods: Acetic acid was used to induce chronic gastric ulcers in rats, and a water extract of H. pylori was given by mouth every day. Connexin 32 formation was assessed using Western blotting as previously described. The frequencies of proliferating cell nuclear antigen staining and of TdT‐mediated dUTP‐biotin nick end labelling were examined.

Results: In untreated rats, acetic acid‐induced gastric ulcers healed after 14 days and the electrophoretic band corresponding to connexin 32 appeared 4 days after ulcer induction. Treatment with a water extract of H. pylori delayed ulcer healing, with the ulcers remaining unhealed even on the 14th day; healing was delayed more when treatment was with an extract of CagA‐positive rather than CagA‐negative H. pylori. Connexin 32 appeared earlier when treatment was with a CagA‐negative rather than a CagA‐positive extract, but in both cases later than in the untreated control group. Proliferating cell nuclear antigen labelling on the fourth day was seen in 14.5% ± 1.6% of mucosal cells of control group, but in 35.9% ± 1.4% and 36.5% ± 1.4% of mucosal cells treated with either VacA(+)CagA(–) and VacA(+)CagA(+) H. pylori extract, respectively. Furthermore, extracts of both H. pylori strains, especially VacA(+)Cag(+) H. pylori promoted apoptosis.

Conclusions: A water extract of H. pylori increased both proliferation and apoptosis, which are related to excerbation and healing of ulcer as well as appearance of connexin 32.
Review article: control of gall‐bladder motor function
Authors: Shaffer E. A.
Published: March 2003

Muscular contraction of the gall‐bladder is the primary determinant of bile delivery into the duodenum. Where bile goes following its secretion by the liver depends upon a co‐ordinated series of pressure interrelations between the hepatic secretory pressure at the entrance to the biliary system, a low pressure conduit, and the pressure differences between the gall‐bladder, cystic duct and sphincter of Oddi. During fasting, the relatively higher tone in the sphincter of Oddi fosters the entry of bile into the gall‐bladder. The gall‐bladder accommodates this influx without an increase in intravesicular pressure through its compliance or distensibility, which consists of active muscle relaxation and passive fibroelastic components. The concentrating function of the gall‐bladder keeps the volume small. Once about every 120 min during the interdigestive period, gall‐bladder emptying occurs coincident with intense duodenal contractions, all part of the migratory myoelectric complex. This helps maintain the enterohepatic circulation of bile salts. Motilin, which mediates these events during fasting, acts by stimulating intrinsic cholinergic nerves. Cholecystokinin is the major determinant of gall‐bladder emptying with eating. Cholecystokinin acts through pre‐ganglionic cholinergic nerves, to initiate gall‐bladder contraction. Agonists like cholecystokinin and acetylcholine cause contraction of gall‐bladder smooth muscle through signal transduction, which increases intracellular calcium levels and so initiates the contractile machinery. Cholecystokinin also acts on the sphincter of Oddi via pre‐ganglionic cholinergic nerves to release vasoactive intestinal polypeptide and nitric oxide, and so lower tone. These events are co‐ordinated with motility and secretory events in the upper gastrointestinal tract, delivering bile at appropriate times into the duodenum.
Helicobacter pylori, mucosal inflammation and symptom perception – new insights into an old hypothesis
Authors: Stanghellini V. , Barbara G. , De Giorgio R. , Tosetti C. , Cogliandro R. , Cogliandro L. , Salvioli B. , Corinaldesi R.
Published: March 2003

The role of Helicobacter pylori and the accompanying mucosal inflammatory response in functional dyspepsia is still undefined. Human and animal studies have clearly demonstrated a link between intestinal mucosal inflammation and changes in sensory‐motor function. Growing clinical and basic evidence supports the concept that a similar paradigm may occur in H. pylori‐related dyspepsia. The infection may both induce gastric dysmotility and trigger neuroplastic changes in the afferent neural pathways leading to visceral hyperalgesia. A reduction of central antinociceptive control systems may also play a pathophysiological role.

H. pylori eradication has provided disappointing results in terms of improvement of symptoms. This may reflect the long‐term recovery of neuroplastic changes occurring in the afferent nervous system or, alternatively, the incomplete resolution of gastritis and the persistent production of inflammatory mediators by resident cells in the muscularis externa.

The identification of these mechanisms may provide a better understanding of the pathophysiology of H. pylori‐related dyspepsia and prompt innovative therapeutic approaches.
The gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase‐2, in humans
Authors: Hawkey C. J. , Jackson L. , Harper S. E. , Simon T. J. , Mortensen E. , Lines C. R.
Published: March 2003

Highly selective inhibitors of cyclooxygenase‐2, such as rofecoxib, are hypothesized to have an improved gastrointestinal tolerability and safety profile compared with non‐selective NSAIDs, which inhibit cyclooxygenase‐1 and cyclooxygenase‐2 non‐selectively. This paper reviews data from randomized, double‐blind, placebo‐controlled studies which investigated the effects of rofecoxib and NSAIDs on the human gastrointestinal tract.

In healthy subjects, rofecoxib 25 mg and 50 mg daily had no effect on gastric mucosal prostaglandin synthesis, whilst naproxen 1000 mg daily caused a 70% reduction. Therapeutic doses of rofecoxib 25 mg and 50 mg daily did not increase intestinal permeability or faecal blood loss in healthy subjects, whereas increases in both measures were seen with indometacin 150 mg or ibuprofen 2400 mg. A supra‐therapeutic dose of rofecoxib (250 mg) given daily for 7 days did not induce an increase in gastroduodenal erosions in healthy subjects, whilst increased numbers of erosions were found in subjects given ibuprofen 2400 mg or aspirin 2600 mg.

The endoscopic findings in healthy subjects were confirmed in two 6‐month clinical studies involving 1516 patients with osteoarthritis; the incidences of ulcers following rofecoxib 25 mg or 50 mg daily were similar to placebo and less than ibuprofen 2400 mg. The advantage of rofecoxib over NSAIDs in these studies appears to translate into clinically relevant benefits; an analysis of 5435 patients with osteoarthritis found a significantly lower incidence of gastrointestinal perforations, ulcers and bleeds in patients taking rofecoxib compared with patients taking NSAIDs.

Overall, the findings from these studies suggest that, as a result of cyclooxygenase‐1 sparing, rofecoxib is significantly less gastrotoxic than non‐selective NSAIDs, and may not differ from placebo.
Maximal acid reflux control for Barrett’s oesophagus: feasible and effective
Authors: Srinivasan R. , Katz P. O. , Ramakrishnan A. , Katzka D. A. , Vela M. F. , Castell D. O.
Published: March 2003

Introduction:

The treatment of patients with Barrett’s oesophagus is controversial. Debate exists regarding the use and value of high dose acid suppression as the standard of practice. Despite prolonged use of high dose proton pump inhibitors (40 mg omeprazole, 60 mg lansoprazole), most studies have shown no convincing evidence of significant regression of Barrett’s length. These studies, however, have used fixed doses of proton pump inhibitors and did not regularly document control of oesophageal acid exposure.

Aim:

To determine whether regression of Barrett’s epithelium can be achieved with documented maximal acid suppression.

Methods:

We have prospectively followed nine patients with Barrett’s oesophagus (eight male; mean age 60 years) for more than 1 year. They were all treated using medical therapy with pH monitoring documenting oesophageal acid exposure over 24 h < 1.6% of the time, and with two or more esophagogastroduodenoscopies performed by the same endoscopist.

Results:

Acid control was individually tailored and achieved with proton pump inhibitor b.d. (omeprazole 20 mg or lansoprazole 30 mg) and ranitidine at bedtime (HS) (Ran) if necessary. All nine patients (100%) showed some evidence of regression. All nine patients (100%) showed a decrease in Barrett’s length (mean 2 cm, range 1–3 cm). Six out of nine (66.67%) patients showed evidence of squamous islands on the last oesophagogastroduodenoscopy. The mean total distal oesophageal acid exposure was 0.38% (range: 0–1.5%). The mean follow‐up of patients was 54 months (range: 13–118 months).

Conclusions:

Consistent and individually tailored maximal acid suppression documented by pH‐metry is achievable and may result in decreased length and development of squamous islands in patients with Barrett’s epithelium. This approach should be further evaluated as potentially the preferred medical treatment for these patients.
Review article: the risk of lymphoma associated with inflammatory bowel disease and immunosuppressive treatment
Authors: Aithal G. P. , Mansfield J. C.
Published: March 2003

Lymphoma complicating inflammatory bowel disease is well described. Whether the risk of lymphoma is incre‐ ased by immunosuppressive treatment with azathiop‐ rine, 6‐mercaptopurine or infliximab is a common concern among patients and physicians considering using these agents. This review aims to quantify the lymphoma risk in inflammatory bowel disease and the added risk attributable to these treatments.

The evidence from published cases is that lymphomas occur at sites of active inflammatory bowel disease more often than expected for this to be a chance association. Studies on inflammatory bowel disease populations are conflicting, with some follow‐up studies from large inflammatory bowel disease clinics showing an increase in lymphoma incidence, while other population‐based studies show little or no increase in risk of lymphoma. A small increase in lymphoma risk in inflammatory bowel disease, perhaps 2–3‐fold, may be compatible with both sets of data.

Studies of the risks associated with immuno‐ suppression are less satisfactory, with smaller numbers of patients and relatively short follow‐up. The available evidence would support a further increase in lymphoma risk associated with immunosuppressive treatment in inflammatory bowel disease of around fivefold compared to no immunosuppressive use, and tenfold compared to the general population. The risks appear to be less than that associated with renal and hepatic transplant‐related immunosuppression. Infliximab treatment is still too new to make a full assessment of its long‐term safety, but post‐marketing surveillance currently suggests that lymphoma risk may not be any greater than that associated with azathioprine and 6‐mercaptopurine.

Population‐wide surveillance for lymphoma in inflammatory bowel disease would be required to narrow the confidence intervals on these estimates of lymphoma risk in inflammatory bowel disease and immunosuppressive treatment.
Outcomes of Helicobacter pylori treatment in community practice and impact of therapeutic effectiveness information on physician behaviour
Authors: Fennerty M. B. , Magaret N. , Dalros L. , Faigel D. , Lieberman D. , Shaw M.
Published: March 2003

Background:

The effect of knowledge of Helicobacter pylori eradication rates on physician choice of treatment regimen is unknown. As practice variation results in differences in outcome, it is important to determine whether physician behaviour can be altered by such knowledge.

Aims:

(i) To determine whether dissemination of practice variation and effectiveness data regarding H. pylori changes subsequent prescribing behaviour and (ii) whether this change results in an improvement in the effectiveness of therapy.

Methods:

Community gastroenterologists in the Portland metropolitan area enrolled patients being treated for H. pylori. The regimen used, diagnostic method, indication and success in eradication was measured. Patient‐centred factors were also measured, including symptoms, interest in post‐treatment diagnostic testing and willingness to pay.

Results:

Significantly more physicians participating in both studies used proton pump inhibitor–triple therapy based regimens in this trial (46% vs. 85%, P=0.01), although the overall difference between the two trials was not significant (62% vs. 83%, P=0.11). There was no change in overall eradication rates by per protocol analysis between trials (84% vs. 85%, P=0.78), but a significant decrease in effectiveness by intention‐to‐treat analysis observed in this study (80% vs. 71%, P=0.03). Significantly more patients were treated for reasons other than peptic ulcer disease in this study (P=0.0003).

Conclusions:

The overall effectiveness of H. pylori therapy in practice remains good. There has been a shift in the choice of treatment regimen and indication for therapy between the time periods of the two studies. Dissemination of treatment data appears to effect prescribing behaviour, but whether it has a beneficial effect on treatment outcome remains unproven.
The role of age and salivation in acid clearance in symptomatic patients with gastro‐oesophageal reflux disease
Authors: Orr W. C. , Chen C.‐L. , Sloan S.
Published: March 2003

Background:

Cisapride has been shown to have not only prokinetic effects, but also salivary stimulating effects. Both of these mechanisms play an important role in the acid clearance of the oesophagus.

Aim:

To access the efficacy of cisapride in facilitating acid clearance in patients with symptomatic gastro‐oesophageal reflux disease.

Methods:

Fifteen older adults and 15 younger adults with symptomatic gastro‐oesophageal reflux disease completed the study. The acid clearance test was accomplished by infusing 15 mL of 0.1 NHCl into the distal oesophagus, and the number of swallows was determined to achieve an oesophageal pH of 4.0. This was accomplished under baseline conditions and salivary stimulation with a peppermint lozenge. After 1 week of treatment with cisapride (10 mg, q.d.s.), the acid clearance test was repeated.

Results:

The lozenge produced a significant decrease in the number of swallows compared to baseline in both groups (P < 0.01). There was a significant decrease in the number of swallows after the treatment with cisapride compared to baseline in both groups (P < 0.01). No significant difference was found in the number of swallows when comparing cisapride with lozenge.

Conclusions:

Cholinergic stimulation of salivation is an effective means of facilitating oesophageal acid clearance. Drugs, such as 5 hydroxytriptamine (5‐HT)4‐receptor agonists, should be considered as potentially important compounds in the treatment of gastro‐oesophageal reflux disease.
Plasma transforming growth factor‐β1 level and efficacy of α‐tocopherol in patients with non‐alcoholic steatohepatitis: a pilot study
Authors: Hasegawa T. , Yoneda M. , Nakamura K. , Makino I. , Terano A.
Published: March 2003

Background:

Non‐alcoholic steatohepatitis is a distinct entity, characterized by fatty change, lobular inflammation and fibrosis of the liver. Some cases of non‐alcoholic steatohepatitis progress to cirrhosis, but it is not easy to distinguish this disease from non‐alcoholic fatty liver by non‐invasive examinations. No proven therapy for non‐alcoholic steatohepatitis exists. Transforming growth factor‐β1 is implicated in the development of liver fibrosis, and is inhibited by α‐tocopherol (vitamin E) in the liver. Therefore, in this study, the significance of the measurement of the level of plasma transforming growth factor‐β1 and the effect of α‐tocopherol on the clinical course of non‐alcoholic steatohepatitis were investigated.

Methods:

Twelve patients with non‐alcoholic steatohepatitis and 10 patients with non‐alcoholic fatty liver, with a diagnosis confirmed by liver biopsy, were studied. None of the patients had a history of alcohol abuse, habitual medicine or malignant or inflammatory diseases. All patients were negative for hepatitis B, C and G virus. Patients were given dietary instruction for 6 months, and then α‐tocopherol (300 mg/day) was given for 1 year. Blood chemistries, measurement of plasma transforming growth factor‐β1 level and liver biopsies were undertaken before and after the 1‐year α‐tocopherol treatment.

Results:

The serum alanine transaminase level decreased in non‐alcoholic fatty liver patients, but not in non‐alcoholic steatohepatitis patients, after 6 months of dietary therapy. Although the serum alanine transaminase level in non‐alcoholic steatohepatitis patients was reduced during the 1‐year α‐tocopherol treatment, α‐tocopherol had no effect on the serum alanine transaminase level in non‐alcoholic fatty liver patients. The histological findings, such as steatosis, inflammation and fibrosis, of the non‐alcoholic steatohepatitis patients were improved after α‐tocopherol treatment. The plasma transforming growth factor‐β1 level in non‐alcoholic steatohepatitis patients was significantly elevated compared with that in non‐alcoholic fatty liver patients and healthy controls, and decreased, accompanied by an improvement in serum alanine transaminase level, with α‐tocopherol treatment.

Conclusions:

lOur data suggest that the measurement of the level of plasma transforming growth factor‐β1 represents a possible method of distinguishing between non‐alcoholic steatohepatitis and non‐alcoholic fatty liver. Long‐term α‐tocopherol treatment may be safe and effective for non‐alcoholic steatohepatitis. A randomized, controlled, double‐blind trial is needed to confirm the full potential of α‐tocopherol in the management of non‐alcoholic steatohepatitis.
Randomized controlled trial of clarithromycin and ethambutol in the treatment of Crohn’s disease
Authors: Goodgame R. W. , Kimball K. , Akram S. , Ike E. , Ou C.‐N. , Sutton F. , Graham D.
Published: March 2003

Background:

A mycobacterial infection may be the cause of Crohn’s disease in some patients. Measurement of intestinal permeability may identify Crohn’s disease patients with a high likelihood of relapse and may quantify the severity of intestinal injury.

Aim:

To assess the effect of 3 months of clarithromycin and ethambutol on the disease activity and intestinal permeability in patients with Crohn’s disease at high risk of relapse.

Methods:

Patients with Crohn’s disease, with a lactulose–mannitol permeability test above 0.03, were randomly assigned to receive either clarithromycin, 500 mg twice daily, and ethambutol, 15 mg/kg daily, or identically appearing placebo for 3 months in addition to their regular therapy. The Harvey–Bradshaw index and the lactulose–mannitol test were assessed in a blind fashion every 3 months for 12 months.

Results:

Thirty‐one patients were randomized to receive either drugs (n=15) or placebo (n=16). The groups were similar in age, sex, duration of disease, location of disease, past complications and disease severity. Specifically, there was no difference between the drug or placebo groups in the mean Harvey–Bradshaw index (4.8 vs. 4.4), number with active disease (33% vs. 44%) and mean lactulose–mannitol test (0.06 vs. 0.10). During the 12‐month follow‐up period, there were no consistent, statistically significant differences in the mean Harvey–Bradshaw index or lactulose–mannitol test between treatment and placebo groups. Individual patients showed either improvement or worsening of these indices, but these were not related to study medication. Specifically, no ‘cures’ were noted with anti‐mycobacterial treatment.

Conclusions:

Three months of treatment with clarithromycin and ethambutol does not benefit Crohn’s disease patients who are receiving standard medical therapy.
Rabeprazole‐based 3‐day and 7‐day triple therapy vs. omeprazole‐based 7‐day triple therapy for the treatment of Helicobacter pylori infection
Authors: Wong B. C. Y. , Wong W. M. , Yee Y. K. , Hung W. K. , Yip A. W. C. , Szeto M. L. , Li K. F. , Lau P. , Fung F. M. Y. , Tong T. S. M. , Lai K. C. , Hu W. H. C. , Yuen M. F. , Hui C. K. , Lam S. K.
Published: March 2003

Background:

Rabeprazole is a new proton pump inhibitor with more potent acid suppressive and anti‐Helicobacter effects.

Aim:

To compare two different regimens of rabeprazole‐based triple therapy vs. 7‐day omeprazole‐based triple therapy for the eradication of Helicobacter pylori infection.

Method:

Patients with proven H. pylori infection were randomized to receive: (i) 7‐day rabeprazole, 10 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; (ii) 3‐day rabeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; or (iii) 7‐day omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily. Endoscopy (CLO test, histology) was performed before randomization and 6 weeks after drug treatment.

Results:

One hundred and seventy‐three patients were randomized. H. pylori eradication rates (intention‐to‐treat, n=173/per protocol, n=167) were 88%/91% for 7‐day rabeprazole‐based therapy, 72%/72% for 3‐day rabeprazole‐based therapy and 82%/89% for 7‐day omeprazole‐based therapy, respectively. The per protocol eradication rate was significantly better in the 7‐day rabeprazole‐based therapy and 7‐day omeprazole‐based therapy groups when compared to the 3‐day rabeprazole‐based therapy group (P=0.01 and P=0.04, respectively). Compliance was excellent and all three regimens were well tolerated.

Conclusions:

The efficacy of seven‐day rabeprazole‐based triple therapy is similar to 7‐day omeprazole‐based triple therapy for the eradication of H. pylori infection.
The efficacy of thymosin in the treatment of chronic hepatitis B virus infection: a meta‐analysis
Authors: Chan H. L.‐Y. , Tang J.‐L. , Tam W. , Sung J. J.‐Y.
Published: March 2003

Background:

Trials of thymosin treatment in chronic hepatitis B virus infection have been small and the results have been inconsistent.

Aim:

To conduct a meta‐analysis to evaluate the efficacy of thymosin treatment in chronic hepatitis B virus infection.

Methods:

Randomized controlled trials comparing thymosin for over 24 weeks vs. placebo (or usual care) in the treatment of chronic hepatitis B virus infection were identified through MEDLINE, EMBASE and the Cochrane Register of Clinical Trials. Biochemical (normalization of transaminases) and virological (loss of hepatitis B virus DNA and hepatitis B e antigen) responses were analysed using the intention‐to‐treat method. The odds ratio was used to measure the magnitude of the efficacy.

Results:

Five trials (353 patients) were identified. The odds ratio (95% confidence interval) of the virological response of thymosin over placebo at the end of treatment, 6 months post‐treatment and 12 months post‐treatment were 0.56 (0.2–1.52), 1.67 (0.83–3.37) and 2.67 (1.25–5.68), respectively. There was an increasing trend of the virological response with time since the cessation of thymosin treatment (P=0.02). There was no difference in the biochemical response between the thymosin and placebo groups at the end of treatment, 6 months post‐treatment and 12 months post‐treatment.

Conclusions:

Thymosin is effective in suppressing viral replication in chronic hepatitis B virus infection, but the effect is delayed until 12 months after the cessation of treatment.
Effects of 5‐HT3 antagonism on postprandial gastric volume and symptoms in humans
Authors: Kuo B. , Camilleri M. , Burton D. , Viramontes B. , McKinzie S. , Thomforde G. , O'Connor M. K. , Brinkmann B. H.
Published: March 2003

Background:

Alosetron reduces symptoms of dyspepsia, but the physiological basis for the symptomatic benefit is unclear.

Aim:

To assess 5‐HT3 antagonism on postprandial gastric volume and symptoms after ingestion of maximum tolerable volume of a liquid meal.

Methods:

In 36 healthy volunteers, we assessed effects of placebo, 0.5 and 1 mg b.d. alosetron on fasting and postprandial gastric volumes (using single photon emission computed tomography) and symptoms based on 100 mm VAS, 30 min after maximum volume ingested.

Results:

The 5‐HT3 antagonist reduced postprandial symptoms (aggregate score: P < 0.05), nausea (P < 0.001), and tended to reduce bloating (P=0.08). Both 0.5 and 1 mg alosetron reduced nausea (P < 0.025); 1 mg alosetron reduced aggregate symptoms (P < 0.05) and bloating (P < 0.05). Effects on pain (P=0.19) and fullness (P=0.14) were not statistically significant. There were no significant effects of the 5‐HT3 antagonist on volume of meal tolerated or on SPECT‐measured fasting or postprandial gastric volumes.

Conclusion:

5‐HT3 antagonism reduces aggregate symptoms, nausea and bloating after a liquid meal without increase in gastric volumes, suggesting a role for 5‐HT3 in afferent functions in healthy humans during the postprandial period.
Serum pepsinogen and gastrin levels in HIV‐positive patients: relationship with CD4+ cell count and Helicobacter pylori infection
Authors: Fabris P. , Pilotto A. , Bozzola L. , Tositti G. , Soffiati G. , Manfrin V. , De Lalla F.
Published: March 2003

Background:

The relationship between serum parameters of gastric function and Helicobacter pylori infection in human immunodeficiency virus (HIV)‐positive patients is almost unknown.

Aims:

To investigate in HIV‐infected patients: (i) the relationship between serum gastrin and serum pepsinogens over the progressive phases of HIV‐related disease; (ii) the impact of H. pylori infection on gastrin and pepsinogen serum levels and its relation to antral histology; (iii) the prevalence of parietal cell autoantibodies.

Methods:

Fifty‐nine HIV‐positive patients were studied by upper endoscopy plus gastric antral biopsy. Serum samples were tested for gastrin, pepsinogen A, pepsinogen C and parietal cell autoantibodies.

Results:

In patients without overt acquired immunodeficiency syndrome (AIDS), or with a CD4+ count of > 100 × 106 cells/L, mean serum levels of gastrin and pepsinogen C were higher than in subjects with AIDS or with a CD4+ count of < 100 × 106 cells/L (P < 0.01). Only one patient was found to be positive for parietal cell autoantibodies. H. pylori infection was associated with increased values of gastrin and pepsinogen C only in HIV‐positive patients without AIDS or with a CD4+ count of > 100 × 106 cells/L. Atrophy was more frequent in patients with overt AIDS than in those without overt AIDS (57% vs. 33%, P=N.S.), and/or in patients with a CD4+ count of < 100 × 106 cells/L than in those with a CD4+ count of > 100 × 106 cells/L (62% vs. 26%, P < 0.05).

Conclusions:

HIV‐positive patients without overt AIDS have increased serum levels of gastrin and pepsinogen C compared with HIV‐positive patients with overt AIDS.
Ranitidine, 75 mg, over‐the‐counter dose: pharmacokinetic and pharmacodynamic effects in children with symptoms of gastro‐oesophageal reflux
Authors: Orenstein S. R. , Blumer J. L. , Faessel H. M. , McGuire J. A. , Fung K. , Li B. U. K. , Lavine J. E. , Grunow J. E. , Treem W. R. , Ciociola A. A.
Published: March 2003

Background:

The use of over‐the‐counter antacids has increased in children under the age of 12 years, and has been followed by an apparent increase in the use of over‐the‐counter histamine‐2 receptor antagonists. However, the pharmacokinetic and pharmacodynamic effects of over‐the‐counter histamine‐2 receptor antagonists in the paediatric population are largely unknown.

Aim:

To evaluate the pharmacokinetics and pharmacodynamics of a single dose of the over‐the‐counter histamine‐2 receptor antagonist, ranitidine, 75 mg, in children with symptoms of gastro‐oesophageal reflux disease.

Methods:

Children aged between 4 and 11 years with symptoms of heartburn suspected to be due to gastro‐oesophageal reflux disease were recruited at six clinical centres. Following a single dose of either oral ranitidine, 75 mg (n=19), or placebo (n=10), recording of intragastric pH and serial blood sampling were carried out for 6 h.

Results:

The estimated pharmacokinetic parameters of ranitidine, 75 mg, were as follows: the median Cmax value of 477 ng/mL occurred within a median of 2.5 h after dosing, and the median half‐life was 2.0 h. The intragastric pH began to rise approximately 30 min after dosing with ranitidine to a peak of pH ˜ 4. The pH in the ranitidine group remained higher than that in the placebo group throughout the 6‐h evaluation period. Adverse events were generally mild.

Conclusions:

Ranitidine, 75 mg, significantly increased the intragastric pH in children aged 4–11 years. The pharmacokinetic and pharmacodynamic profiles were similar to those in adults. Ranitidine, 75 mg, appears to be effective for the control of intragastric acidity for 5–6 h in children aged 4–11 years.
Extra‐intestinal manifestations associated with irritable bowel syndrome: a twin study
Authors: Svedberg P. , Johansson S. , Wallander M.‐A. , Hamelin B. , Pedersen N. L.
Published: March 2003

Background:

Little is known about the role of genetic and environmental factors in irritable bowel syndrome. Various extra‐intestinal manifestations are more prevalent in cases than in controls. Genetic effects may be important in the liability to develop functional bowel disorders.

Aims:

To evaluate the associations of irritable bowel syndrome with several disorders co‐morbid with the condition, using both a case–control design and a co‐twin control design.

Methods:

A sample of 850 Swedish twin pairs, aged 18–85 years, was contacted for a telephone interview. Through a diagnostic algorithm, 72 unrelated cases of irritable bowel syndrome and 216 age‐ and gender‐matched controls were identified. Fifty‐eight twin pairs discordant for irritable bowel syndrome were evaluated in co‐twin analyses.

Results:

Renal problems (odds ratio (OR)=3.3; confidence interval (CI), 1.3–8.2), obesity (OR=2.6; CI, 1.0–6.4), underweight in the past (OR=2.4; CI, 1.1–6.4), gluten intolerance (OR=9.0; CI, 1.4–60.1), rheumatoid arthritis (OR=3.2; CI, 1.1–9.4) and poor self‐rated health (OR=1.8; CI, 1.0–3.2) were significantly associated with irritable bowel syndrome. In the co‐twin analyses, the only factors maintaining significance were renal and recurrent urinary tract problems.

Conclusions:

The association between irritable bowel syndrome and renal and urinary tract problems does not reflect a genetic or familial mediation. Eating disorders in childhood represent a familial–environmental influence on irritable bowel syndrome, whereas the association with rheumatoid arthritis and perhaps gluten intolerance probably reflects genetic mediation.