bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: gene therapy in gastroenterology and hepatology
Authors: FORBES S. J. , HODGSON H. J. F.
Published: October 2003

Gene therapy for diseases of the gastrointestinal tract is an exciting prospect because of the fundamental cure that is potentially available. The gastrointestinal system, and especially the liver, is an area that will be central to the development of gene therapy.

Techniques for gene replacement include homologous recombination and gene augmentation. For the treatment of cancer antisense strategy, pro‐drug activation systems and gene immunotherapy are being investigated. Gene‐carrying vectors divide into viral‐ and non‐viral‐based vectors, each with advantages and limitations. The accurate delivery of these vectors to sufficient numbers of target cells in vivo is still a major barrier to clinical use.

Diseases that may be helped by gene therapy include: gastrointestinal malignancies, viral hepatitis, the haemophilias, hypercholesterolaemia, α1‐antitrypsin deficiency, and metabolic diseases of the liver and cystic fibrosis.

In this review we will outline the principles of gene therapy, delivery vectors under investigation, diseases that may benefit from this technology and some of the remaining problems to be overcome.
Two omeprazole‐based Helicobacter pylori eradication regimens for the treatment of duodenal ulcer disease in general practice
Authors: COTTRILL M. R. B. , KINNON C. M c , MASON I. , CHESTERS S. A. , SLATCHER G. , COPEMAN M. B. , TURBITT M. L.
Published: October 2003

Background:

Helicobacter pylori is the main acquired factor in the pathogenesis of duodenal ulcer disease.

Methods:

This multicentre study conducted in 32 general practice centres in the UK and Ireland was a double‐blind, placebo‐controlled, randomized, parallel‐group comparison of triple therapy (n = 98: omeprazole 40 mg once daily and amoxycillin 1 g b.d. for 2 weeks, and metronidazole 400 mg t.d.s. for the first week) and dual therapy (n = 85: omeprazole 40 mg once daily and amoxycillin 1 g b.d. for 2 weeks, with placebo during the first week) for the eradication of H. pylori in patients with symptomatic duodenal ulcer disease. Patients who were successfully treated entered a follow‐up phase for 12 months to assess symptomatic relapse and use of health‐care resources.

Results:

Eradication of H. pylori based on a second 13C‐urea breath test was successful in 95% (95% confidence interval (CI) = 90–100%) of patients receiving omeprazole triple therapy and 53% (95% CI = 41–65%) of those receiving omeprazole dual therapy (P < 0.0001 between groups, all data available analysis). The all‐patients‐treated analysis gave eradication rates of 80 and 44% for omeprazole triple therapy and omeprazole dual therapy, respectively. Symptomatic relapse occurred in 16% (18/116) of the H. pylori‐negative patients who entered the 12‐month follow‐up period, and there were significant reductions in the number of consultations, investigations and prescriptions relating to upper gastrointestinal symptoms compared with the 12 months prior to the eradication therapies (all P < 0.0001). The two treatment strategies were comparable in terms of the number of adverse events reported.

Conclusions:

Omeprazole triple therapy provides a highly effective treatment for the eradication of H. pylori infection in patients in general practice, with an adverse event profile similar to that seen with omeprazole dual therapy. The successful eradication of H. pylori with these omeprazole regimens results in a significant decrease in the use of health‐care resources in the 12 months following treatment.
A dose‐ranging pharmacokinetic study of nicotine tartrate following single‐dose delayed‐release oral and intravenous administration
Authors: COMPTON R. F. , SANDBORN W. J. , LAWSON G. M. , SHEETS A. J. , MAYS D. C. , ZINS B. J. , TREMAINE W. J. , LIPSKY J. J. , MAHONEY D. W. , ZINSMEISTER A. R. , OFFORD K. P. , HURT R. D. , EVANS B. K. , GREEN J.
Published: October 2003

Background

Ulcerative colitis is predominantly a disease of non‐smokers, and transdermal nicotine is therapeutic but often results in side‐effects. Administration of nicotine tartrate as a liquid enema decreases systemic nicotine absorption and may be effective for treatment of active distal ulcerative colitis. Ileocolonic delivery of nicotine tartrate via a delayed release oral capsule would be the preferred route to deliver nicotine to the colon.

Aim

: To determine the bioavailability and pharmacokinetic parameters of delayed‐release oral nicotine tartrate capsules (Eudragit S100 coated) at doses of 3 mg and 6 mg nicotine.

Methods

: Twenty healthy human subjects received delayed‐release oral nicotine tartrate at one of two doses (each group n = 10): 3 mg and 6 mg nicotine. All subjects also received intravenous nicotine tartrate (at a dose of 15 μg nicotine base/kg) during a separate study period. Serum nicotine concentrations were determined by gas chromatography–mass spectrometry. In addition, concentrations of serum cotinine (major nicotine metabolite) were determined by high‐performance liquid chromatography in all samples for two subjects (both given 6 mg nicotine). Adverse reactions were determined by questionnaire.

Results

: The mean bioavailabilities of nicotine after ileocolonic nicotine tartrate administration via delayed‐release oral capsules at doses 3 mg and 6 mg nicotine were 41% and 42%, respectively. The ratios (after adjusting for nicotine dose) of cotinine area under the curve (AUC) for delayed‐release oral nicotine to cotinine AUC for intravenous nicotine were 1.5 and 1.6 for the two subjects undergoing cotinine pharmacokinetics, demonstrating significant first‐pass metabolism. Serum nicotine concentrations did not predict adverse reactions.

Conclusions

: Nicotine tartrate delivered to the ileocolon as a delayed‐release oral capsule at doses of 3 mg and 6 mg nicotine considerably reduced systemic nicotine bioavailability. This reduction in bioavailability appears to be a result of first‐pass hepatic metabolism rather than poor mucosal absorption of nicotine. The therapeutic potential of an ileocolonic delivery formulation of nicotine tartrate, which can potentially limit toxicity by local delivery of high doses of nicotine, should be investigated in patients with ulcerative colitis.
One‐year prophylactic efficacy and safety of pantoprazole in controlling gastro‐oesophageal reflux symptoms in patients with healed reflux oesophagitis
Authors: MÖSSNER J. , KOOP H. , PORST H. , WÜBBOLDING H. , SCHNEIDER A. , MAIER C.
Published: October 2003

Background:

Pantoprazole is a benzimidazole derivative which selectively inhibits the proton pump H+, K+‐ATPase necessary for the final step in gastric acid secretion.

Aim:

To investigate the tolerability and the prophylactic effect of pantoprazole 40 mg once daily on relapse in patients whose reflux oesophagitis had been healed.

Methods:

The safety of pantoprazole 40 mg once daily was assessed in an open 1‐year trial on 222 patients whose reflux oesophagitis had been healed with omeprazole or pantoprazole. Relapse was defined as endoscopically‐confirmed reflux oesophagitis (at least Grade I), with endoscopies being performed for patients experiencing 3 consecutive days of disease‐specific symptoms.

Results:

Kaplan–Meier survival analysis at 6 and 12 months gave estimated treatment failure rates of 2% and 6% from confirmed relapses (per‐protocol), and of 9% and 30% for a worst‐case group (all withdrawals counted as failures). The only population shift in laboratory variables was a doubling of the median serum gastrin level over the first 6 months; thereafter it stabilized. Fifty‐four (24%) patients experienced adverse events; 15 of these withdrew. Serious adverse events were reported for 12 patients.

Conclusions:

Pantoprazole appears to be highly effective and to have a good safety profile for long‐term prophylaxis of reflux oesophagitis.
Comparison of two 1‐week low‐dose omeprazole triple therapies— optimal treatment for Helicobacter pylori infection?
Authors: GOH K. L. , PARASAKTHI N. , CHUAH S. Y. , CHEAH P. L. , LO Y. L. , CHIN S. C.
Published: October 2003

Objectives:

To determine and compare the efficacy and tolerability of two 1‐week regimen comprising omeprazole, clarithromycin and amoxycillin or metronidazole in the eradication of Helicobacter pylori, and to determine the influence of bacterial resistance to metronidazole and clarithromycin on the outcome of treatment.

Patients and methods:

Patients with unequivocal evidence of H. pylori infection based on culture, histology and rapid urease test of both antrum and corpus biopsies were recruited for the study. The study was a randomized, investigator‐blind, comparative study. Patients received either omeprazole 20 mg o.m., clarithromycin 250 mg b.d. and amoxycillin 500 mg b.d. (OAC) or omeprazole 20 mg o.m., metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC) for 1 week. Patients were assessed for successful eradication, which was defined as absence of bacteria in all tests (culture, histology and urease test on both antral and corpus biopsies), at least 4 weeks after completion of therapy.

Results:

Eighty‐two patients were recruited for the study. Eradication rates on intention‐to‐treat analysis were—OAC: 36/41 (87.8%, 95% CI: 73.8, 95.9); OMC: 33/41 (80.5%, 95% CI: 65.1, 91.2). On per protocol analysis were—OAC: 36/40 (90%, 95% CI: 76.3, 97.2); OMC: 32/38 (84.2%, 95% CI: 68.7, 94.0). All side‐effects encountered were mild and no patient discontinued treatment because of intolerance to medications. The most common side‐effects were altered taste (OAC 31.7%, OMC 53.7%) and lethargy (OAC 14.6%, OMC 19.5%). Pre‐treatment metronidazole resistance was encountered in 34/63 (54.0%) patients. No bacterial strains were found with primary resistance to clarithromycin. Metronidazole resistance did not significantly affect eradication rates. Emergence of resistance to clarithromycin was not seen post‐therapy.

Conclusions:

Both the OAC and the OMC regimens were convenient and well‐tolerated treatments for H. pylori. However, eradication rates were lower than anticipated.
Four‐day quadruple therapy as a routine treatment for Helicobacter pylori infection
Authors: BOER S. Y. DE , SIEM T. H.
Published: October 2003

Background:

H. pylori eradication usually involves treatment with three or four drugs for at least 7 days. Possible advantages of short treatment regimens are better patient compliance and tolerability, and less adverse effects. Recently two reports have shown a cure rate of > 90% using a 4‐day quadruple therapy.

Aim:

To confirm these data and to evaluate the efficacy and tolerability of 4‐day quadruple therapy in a single centre.

Methods:

Thirty‐eight consecutive patients with non‐ulcer dyspepsia or peptic ulcer disease, and proven H. pylori infection, received 4 days of quadruple therapy (bismuth, tetracycline, metronidazole, lansoprazole). At least 6 weeks after treatment, endoscopy was repeated with six biopsies of antrum and corpus for histology and culture.

Results:

The intention‐to‐treat cure rate was 34/38 (89.5%, 95% CI: 79.7–99.2%). In the per protocol analysis the cure rate was 34/37 (91.9%, 95% CI: 83.1–100%). Primary metronidazole resistance was observed in two patients; both were cured. Metronidazole resistance induction was observed in one patient in whom therapy failed. The treatment was generally well tolerated.

Conclusion:

Routine use of 4‐day quadruple anti‐H. pylori treatment is effective and well tolerated.
Treatment of ulcerative colitis with an engineered human anti‐TNFα antibody CDP571
Authors: EVANS R. C. , CLARKE L. , HEATH P. , STEPHENS S. , MORRIS A. I. , RHODES J. M.
Published: October 2003

Background:

Tumour Necrosis Factor‐alpha (TNFα) is a pro‐inflammatory cytokine whose expression is increased in the colonic mucosa of patients with active ulcerative colitis. TNFα antibodies have been shown to be beneficial in animal models of bowel inflammation and in Crohn's disease but have not previously been studied in ulcerative colitis.

Methods:

Patients with mild/moderate ulcerative colitis were treated openly with a single intravenous infusion of 5 mg/kg of an engineered human IgGγ4 antibody CDP571 and monitored for 8 weeks.

Results:

Fifteen patients entered the study, eight males and seven females, with a mean age of 44 years. Eleven had left‐sided disease, four extensive disease and six patients were steroid‐unresponsive. The treatment was well tolerated and plasma half‐life of CDP571 was ≈7 days. There was a significant reduction from 6.7 to 4.6 (P = 0.023) in the mean Powell–Tuck score by 1 week post‐infusion and a reduction to 5.5 was seen at 2 weeks (P = 0.218). Significant but modest reductions also occurred in erythrocyte sedimentation rate and serum C reactive protein in the first 2 weeks. Mean Interleukin‐6 plasma concentrations fell from 6.9 to 5.4 pg/mL by week 1, and to 6.1 pg/mL by week 2 (NS). Reductions in sigmoidoscopic score and number of liquid stools were noted but failed to reach statistical significance.

Conclusion:

A consistent improvement in disease activity was seen in the initial 2 weeks after infusion and the treatment was well tolerated. These promising results support the testing of CDP571 in a larger controlled trial.
Treatment of corticosteroid‐resistant ulcerative colitis with heparin —a report of 16 cases
Authors: EVANS R. C. , WONG V. SHIM , MORRIS A. I. , RHODES J. M.
Published: October 2003

Background:

Heparin, a group of sulphated glycosaminoglycans, in addition to its anticoagulant activity, has a wide range of potentially anti‐inflammatory effects. These include inhibition of neutrophil elastase and inactivation of chemokines. Previous reports of fortuitous improvement in ulcerative colitis patients treated with heparin for prophylaxis of venous thrombosis, prompted us to perform a pilot study in patients with corticosteroid‐resistant ulcerative colitis.

Methods:

Sixteen hospitalized patients in relapse from ulcerative colitis and unresponsive to high‐dose corticosteroid therapy were treated with intravenous standard heparin (subcutaneous in two patients), the dose was adjusted to provide standard anticoagulant activity. Five patients continued with subcutaneous injections on discharge, with a gradual reduction in the frequency of doses.

Results:

Within 1 week of starting heparin, 12/16 patients had shown a considerable reduction in stool frequency. After 2 weeks of heparin therapy median stool frequency had improved from 8.0/day (range 6.3–10.0) pre‐treatment to 3.5/day (2.5–5.25) (P=0.008), and by 4 weeks 12/16 achieved clinical remission. Four patients required elective colectomy. Three patients were treated with heparin on a second occasion during a relapse, two failed to respond and required subsequent colectomy. Nine remain well. No serious complications were seen due to the anticoagulant activity, apart from bruising at subcutaneous injection sites.

Conclusion:

The response to heparin in patients with ulcerative colitis resistant to standard therapy is encouraging and supports the previous uncontrolled evidence for a therapeutic effect. A controlled trial of heparin in ulcerative colitis is clearly indicated.
Bismuth carbomer foam enemas for active chronic pouchitis: a randomized, double‐blind, placebo‐controlled trial
Authors: TREMAINE W. J. , SANDBORN W. J. , WOLFF B. G. , CARPENTER H. A. , ZINSMEISTER A. R. , METZGER P. P.
Published: October 2003

Background:

Bismuth carbomer liquid enemas are equivalent to mesalamine enemas for active distal ulcerative colitis.

Aims:

In this study, the efficacy and safety of bismuth carbomer foam enemas for active chronic pouchitis was determined in a placebo‐controlled trial.

Patients:

Forty adult patients with active chronic pouchitis were randomly assigned into either concurrent therapy for pouchitis or no concurrent therapy. Topical corticosteroids and mesalamine were withdrawn prior to the study.

Methods:

Patients received either bismuth carbomer (270 mg elemental bismuth) (n=20) or placebo (n=20) foam enemas for 3 weeks. Clinical assessment was performed at baseline and at 3 weeks using the pouchitis disease activity index score which incorporates symptoms, endoscopy and histology. Serum bismuth concentrations were determined by atomic absorption spectrophotometry.

Results:

At 3 weeks nine of 20 patients (45%) in both the bismuth and placebo groups had improved. Ten patients discontinued prematurely because of worse diarrhoea (three in each group) or abdominal cramping after enema use (one from the bismuth group and three from the placebo group). No other side‐effects were noted. Serum bismuth concentrations were negligible in all patients.

Conclusions:

Bismuth carbomer foam enemas (270 mg bismuth) nightly for 3 weeks are safe but not efficacious for active chronic pouchitis.
Ranitidine bismuth citrate with clarithromycin versus omeprazole with amoxycillin in the cure of Helicobacter pylori infection
Authors: KOLKMAN J. J. , TAN T. G. , POOL M. OUDKERK , KLEEF W. A. VAN , GERAEDTS A. A. M. , TIMMERMAN R. J. , CROBACH L. F. S. J. , NICOLAI J. J. , WOLFF A. A. C. , LAAN J. VAN DER
Published: October 2003

Aim:

To compare the efficacy of ranitidine bismuth citrate plus clarithromycin (RBC–C) vs. omeprazole plus amoxycillin (OME–AMO) in the cure of Helicobacter pylori infection.

Methods:

In this double‐blind, multicentre, parallel‐group study 122 H. pylori‐positive patients with active duodenal ulcer or gastritis, with confirmed history of duodenal ulcer, were randomized to treatment with ranitidine bismuth citrate 400 mg b.d. plus clarithromycin 500 mg b.d. or omeprazole 20 mg b.d. plus amoxycillin 1000 mg b.d. for 14 days, followed by 14 days of ranitidine bismuth citrate 400 mg b.d. or omeprazole 20 mg once daily, respectively, to facilitate ulcer healing. Endoscopy was carried out at the start of the study and 28 days after the end of treatment. At each endoscopy four biopsies were obtained from the antrum and four biopsies from the corpus, for rapid urease test, histology and culture. H. pylori infection was defined as a positive urease test, confirmed by histology or culture. Cure of H. pylori infection was defined as negative urease test, histology or culture from both sites.

Results:

Per‐protocol, all‐patients‐treated and intention‐to‐treat cure rates (95% confidence interval) were, respectively, 90% (81–89%), 90% (82–89%) and 84% (74–93%) for ranitidine bismuth citrate plus clarithromycin, and 39% (27–54%), 44% (31–57%) and 41% (29–53%) for omeprazole plus amoxycillin, P < 0.00001. Both regimens were well tolerated. Eight patients were lost to follow‐up, for lack of efficacy (one patient), adverse events (three patients) or refusal of second endoscopy (four patients).

Conclusion:

Ranitidine bismuth citrate 400 mg b.d. with clarithromycin 500 mg b.d. is superior to omeprazole 20 mg b.d. with amoxycillin 1000 mg b.d. Ranitidine bismuth citrate with clarithromycin is the first dual therapy with high cure rates and good tolerance, and is easy to take. It may therefore prove a suitable first‐line treatment in H. pylori infection.
Susceptibility of Helicobacter pylori isolates to metronidazole, clarithromycin and amoxycillin in vitro and in clinical treatment in Japan
Authors: MIYAJI H. , AZUMA T. , ITO S. , SUTO H. , ITO Y. , YAMAZAKI Y. , SATO F. , HIRAI M. , KURIYAMA M. , KATO T. , KOHLI Y.
Published: October 2003

Background:

Primary and acquired resistance to antibiotics is an important factor in determining the reason for treatment failure in Helicobacter pylori infection. We examined the relationship between the susceptibility of H. pylori isolates and the efficacy of chemotherapy.

Methods:

The minimal inhibitory concentrations (MICs) of metronidazole (MNZ), clarithromycin (CLAR) and amoxycillin (AMOX) of 320 H. pylori pre‐treatment isolates were determined by the agar dilution method. In 290 patients with peptic ulcers, H. pylori infection was treated by dual or triple combination therapies for 2 weeks: one proton pump inhibitor (30 mg/day lansoprazole or 20 mg/day omeprazole) and one or two antibiotics (500 mg AMOX, 200 mg CLAR or 250 mg MNZ twice a day). MICs were also determined after the treatment failure.

Results:

Among the drugs tested, for MNZ and CLAR, 8.1% and 9.1% of the isolates, respectively, were resistant, while no isolate was resistant to AMOX. After unsuccessful treatment using MNZ and CLAR, 66.7% and 70.6% of the isolates changed from sensitive to resistant, respectively. All isolates were sensitive to AMOX after treatment failure.

Conclusions:

The failure of the H. pylori treatment results in the induction of resistance to CLAR and/or MNZ. Regimens with a high cure rate should be used in order to prevent the generation of acquired resistance to antibiotics.
Comparison of mesalazine suppositories in proctitis and distal proctosigmoiditis
Authors: GIONCHETTI P. , RIZZELLO F. , VENTURI A. , BRIGNOLA C. , FERRETTI M. , PERUZZO S. , CAMPIERI M.
Published: October 2003

Background:

Mesalazine suppositories at 500 mg b.d. are a safe and effective treatment for patients with ulcerative proctitis or distal proctosigmoiditis. Recently a mesalazine 1 g suppository (Pentasa) has been developed.

Methods:

Fifty patients with active ulcerative colitis extending not beyond 20 cm from the anus on sigmoidoscopy, participated in a randomized single‐blind study comparing the efficacy, tolerance and acceptance of the new Pentasa mesalazine 1 g suppository, given once daily versus Claversal mesalazine 500 mg suppository b.d.

Results:

After 2 weeks, clinical remission was observed in 16 of 25 (64%) in the Pentasa group and in 7 of 25 (28%) in the Claversal 500 mg b.d. treated group; sigmoidoscopic remission occurred in 13 of 25 (52%) in the Pentasa group and in six of 25 (24%) in the Claversal group (P < 0.01). After 4 weeks, clinical and sigmoidoscopic remission were observed, respectively, in 84 and 76% of patients treated with Pentasa suppositories, and in 80 and 72% of patients treated with Claversal suppositories 500 mg b.d. (P= N.S.). The patients' evaluation for tolerability and practicality showed that the Pentasa suppository was significantly superior to the Claversal suppository.

Conclusions:

Pentasa 1 g suppository once daily induces a quicker clinical and sigmoidoscopic remission, and was better tolerated, than the Claversal 500 mg suppository b.d., and it may represent an advance for the topical treatment of distal proctosigmoiditis.
Clinical economics review: irritable bowel syndrome
Authors: WELLS N. E. J. , HAHN B. A. , WHORWELL P. J.
Published: October 2003

The ubiquitous nature of irritable bowel syndrome (IBS), coupled with a lack of good treatment options, has created the impression that the condition must represent a large drain on health‐care resources. The literature certainly appears to support this view but is largely based on patients seen in referral centres (10–15%) and it may not be appropriate to extrapolate these data to the IBS population as a whole (85–90%).

In addition to reviewing such literature that exists on the economics of IBS, this paper contains some new data, which suggest that the direct costs of the condition, certainly in the UK, may not be quite as high as has previously been assumed. This may be partly due to factors such as the low cost of the drugs used to treat the condition and the tendency for many patients to stop consulting because of disenchantment with the inadequacies of current therapy. Conversely, the indirect and intangible costs of the disorder appear to be much greater, but these burdens obviously do not have such an impact on those responsible for purchasing and providing health care for IBS sufferers.

Paradoxically, if a new, effective therapy for IBS were forthcoming, the situation could change dramatically, especially if it involved a new drug. Any such agent would inevitably be more expensive than anything available today, leading to a potentially dramatic escalation in the direct costs of this disorder.
Long‐term effect of gluten restriction on bone mineral density of patients with coeliac disease
Authors: BAI J. C. , GONZALEZ D. , MAUTALEN C. , MAZURE R. , PEDREIRA S. , VAZQUEZ H. , SMECUOL E. , SICCARDI A. , CATALDI M. , NIVELONI S. , BOERR L. A. , MAURIÑO E.
Published: October 2003

Aim: To assess the long‐term effect of a gluten‐free diet on bone mineral density of adults with untreated coeliac disease.

Methods: Bone mineral density was assessed at baseline and after a mean duration of 37 months of treatment in 25 unselected newly diagnosed coeliac patients.

Results: At baseline, osteopenia (>−1 s.d. below normal) was evident in the lumbar spine and total skeleton in 18 (72%) and 21 (84%) patients, respectively. At the end of the study, bone density had increased (mean bone mass Z‐score increase: Z‐score +1.0 for the lumbar spine and +1.1 for total skeleton) in 22 and 23 patients, respectively. Patients who adhered to strict gluten restriction (n=15) demonstrated a similar bone remineralization in the spine than those patients with partial compliance (n=10) (mean Z‐score increase: +1.0, in both areas). A greater mean annual change in Z‐score in the total skeleton was noted in patients who followed strict gluten restriction (0.4±0.1) respect to those with partial compliance (0.3±0.1); however, this difference was not statistically significant. Pre‐menopausal women had significantly greater remineralization that post‐menopausals (P>0.05). Remineralization showed an inverse correlation with the degree of basal osteopenia (r=−0.525; P<0.002).

Conclusions: Long‐term treatment with gluten‐free diet produces a significant improvement in bone density in coeliac patients. Remineralization was more pronounced in patients who better comply with gluten‐free diet, in pre‐menopausal women and in patients with the lowest baseline bone mineral density.
Lansoprazole heals erosive reflux oesophagitis in patients with Barrett's oesophagus
Authors: SONTAG S. J. , SCHNELL T. G. , CHEJFEC G. , KURUCAR C. , KARPF J. , LEVINE G.
Published: October 2003

Background: Barrett's oesophagus is thought to be a complication of severe gastro‐oesophageal reflux.

Aim: To determine whether the proton pump inhibitor, lansoprazole, is effective in healing erosive reflux oesophagitis in patients with Barrett's oesophagus.

Methods: An 8‐week, randomized, double‐blind study was conducted using patients with both erosive reflux oesophagitis and Barrett's oesophagus. Erosive reflux oesophagitis was defined as grades 2–4 oesophagitis; Barrett's oesophagus, as specialized columnar epithelium obtained by biopsy from the tubular oesophagus; and healing, as a return to grade 0 or 1 oesophageal mucosa (complete re‐epithelialization). One‐hundred and five (105) patients from one centre were randomized to receive either lansoprazole 30 mg daily or ranitidine 150 mg twice daily. Unhealed or symptomatic lansoprazole patients at week 4 were randomized to receive the same 30 mg dose daily or an increased dose of 60 mg daily. Endoscopy was performed at baseline and at weeks 2, 4, 6 and 8.

Results: The treatment groups were similar in regards to baseline characteristics, erosive reflux oesophagitis grades and length of Barrett's oesophagus. At each 2‐week interval, lansoprazole patients had significantly greater healing rates and less day and night heartburn and regurgitation than ranitidine patients. There were no significant differences between treatment groups in antacid use, quality of life parameters, or rate of reported adverse events. Median values for fasting serum gastrin levels remained within the normal range for both groups.

Conclusion: In patients with both Barrett's oesophagus and erosive reflux oesophagitis, lansoprazole is significantly more effective than ranitidine in relieving reflux symptoms and healing erosive reflux oesophagitis.
Cisapride in functional dyspepsia in general practice. A placebo‐controlled, randomized, double‐blind study
Authors: DE GROOT G. H. , DE BOTH P. S. M.
Published: October 2003

Background: Functional dyspepsia is recognized as a common disorder in clinical practice. The aim of this study was to determine the efficacy and adverse effects of cisapride compared to a placebo in patients from a general practice with functional dyspepsia (FD). Secondly we investigated whether Helicobacter pylori‐positive FD patients present with specific symptoms and determined the efficacy of cisapride for FD patients with H. pylori.

Methods: In a placebo‐controlled double‐blind study, patients were randomized to receive fixed doses of either cisapride (10 mg three times daily) or placebo. Symptoms were evaluated after 2 and 4 weeks of treatment. The selection of FD patients,collection of data, and evaluation of symptoms as well as adverse effects were performed by general practitioners. Dyspeptic patients were referred to the Gastroenterology Department in order to exclude ulcers, oesophagitis, pancreatitis and gallstones. Biopsies of gastric mucosa were taken for histological examination and H. pylori culture.

Patients: 121 patients entered this study (61 took cisapride, 60 placebo). There were 113 patients (56 cisapride, 57 placebo) available for analysis of the efficacy and 120 patients (61 cisapride, 59 placebo) for evaluation of adverse effects.In total 102 biopsies were tested for the presence of gastritis by histological examination. There were 30 H. pylori‐positive cultures among 111 patients.

Results: After 4 weeks a statistically significant reduction in symptoms was found, but it was similar in the two groups. No symptoms specific for H. pylori‐positive patients were found. There was not a significant difference in the response to cisapride between H. pylori‐positive and H. pylori‐negative patients. The difference in overall (63%) response in the cisapride group and the 44% response in the placebo group did not reach statistical significance.

Conclusions: No significant difference was found between placebo and cisapride in the treatment of FD in general practice. H. pylori‐positive patients did not present with specific symptoms nor did they exhibit a different response to cisapride.
Lactulose improves psychometric testing in cirrhotic patients with subclinical encephalopathy
Authors: HORSMANS Y. , SOLBREUX P. M. , DAENENS C. , DESAGER J. P. , GEUBEL A. P.
Published: October 2003

Background: Therapeutic trials suggest that lactulose is an effective treatment of acute and chronic encephalopathy in cirrhotic patients.

Aim and Methods: As it is likely that portal‐systemic shunting and hepatocellular dysfunction are associated with some degree of neurological dysfunction, 14 patients with cirrhosis and documented portal‐systemic shunting, but without detectable encephalopathy, were randomized to treatment with either lactulose 20 g t.d.s., or lactose 20 g t.d.s. as placebo, for a 15‐day period. Monitoring included manually administered and computer‐based psychometric testing, the results of which were correlated with a battery of biochemical and functional parameters.

Results: There was no correlation between biochemical or functional parameters and psychometric testing. There was a close correlation between the time required to complete the number connection test and both the number of errors and the duration of errors at sinusoid testing. Lactulose therapy resulted in a significant improvement, assessed by the number connection test and the race track test.

Conclusion: Our data suggest that lactulose therapy might improve subclinical hepatic encephalopathy in patients with cirrhosis and portal‐systemic shunting.
Rectal steroids suppress bone formation in patients with colitis
Authors: ROBINSON R. J. , IQBAL S. J. , WHITAKER R. P. , ABRAMS K. , MAYBERRY F.
Published: October 2003

Background: The aetiology of bone loss in inflammatory bowel disease is multifactorial, but oral corticosteroids are an important contributory factor. Rectally administered steroids are widely used in patients with distal disease, but very little is known about their effect on bone metabolism. The aim of this study was to investigate the effect of a standard course of rectal prednisolone on biochemical markers of bone turnover.

Methods: In a longitudinal study of 10 patients, biochemical markers of bone turnover were measured before, during and after treatment with prednisolone metasulphobenzoate (Predfoam, Pharmax Ltd) 20 mg twice daily for 2 weeks. Bone formation markers measured were serum osteocalcin (BGP), bone‐specific alkaline phosphatase (BALP) and procollagen carboxy‐terminal propeptide (PICP). Urinary deoxypyridinoline (dPyr) was measured to assess bone resorption.

Results: Disease activity scores improved during treatment (difference in mean Powell–Tuck score=2.3 (±3.1), 95% CI: 0.11–4.48, P=0.04). There was a significant fall in BALP (P=0.02) during treatment, and a rapid but non‐significant fall in BGP (P=0.19). PICP (0.42), and urinary dPyr (0.30) did not change significantly during treatment.

Conclusions: Following a standard 2‐week course of rectal prednisolone metasulphobenzoate, we observed a significant fall in bone‐specific alkaline phosphatase activity. These results suggest that bone formation is suppressed in patients with distal colitis treated with pharmacological doses of rectal steroids.
An evaluation of near‐patient testing for Helicobacter pylori in general practice
Authors: JONES R. , PHILLIPS I. , FELIX G. , TAIT C.
Published: October 2003

Introduction: A knowledge of Helicobacter pylori status is likely to be important in the management of patients presenting in general practice with dyspepsia. Near‐patient testing kits for the detection of the H. pylori antibodies in whole blood, which provide results very quickly, are now available.

Aim: To determine the test characteristics of the Helisal Rapid Blood test in general practice and to describe the ways in which general practitioners incorporate the results of H. pylori testing into their management of patients with dyspepsia.

Setting: Nine general practices in the United Kingdom.

Patients: Consecutive patients presenting with dyspepsia in whom further investigation or referral was considered.

Methods: A whole blood fingerstick sample was tested for H. pylori antibodies using the Helisal Rapid Blood test and a venous sample was obtained for subsequent laboratory testing using Helisal Serum and Helico G (ELISA) methods. Results of the three tests were compared and analysed. Clinical data were recorded by the general practitioners.

Results: Full serological data were obtained on 123 patients, mean age 44.8 years. The sensitivity and specificity of the Helisal Rapid Blood test, compared with concordant results of the laboratory tests, were 83% and 78%, respectively. The prevalence of H. pylori‐positive patients was 57%, with a positive predictive value of 83% and a negative predictive value of 78%. The results of the test had a significant impact on the clinical management of the patients in the study.

Comment: The Helisal Rapid Blood test is a useful and convenient method of improving the clinical care of patients with dyspepsia in general practice.
Effects of octreotide, a somatostatin analogue, on gastric function evaluated by real‐time ultrasonography
Authors: OKAMOTO E. , HARUMA K. , HATA J. , TANI H. , SUMII K. , KAJIYAMA G.
Published: October 2003

Background: Somatostatin exerts inhibitory effects on physiological functions in the gastrointestinal tract. The actions differ, however, depending on the test meal, dose, and other factors.

Aims: To determine by use of ultrasonography and scintigraphy the effect of a somatostatin analog, octreotide, on gastric emptying and antral contraction.

Subjects: Twenty healthy men; mean age 23.9 years

Methods: Subjects were studied for 7 days, once after subcutaneous injection of octreotide, 50 μg, 5 min before the ingestion of a test meal and once after subcutaneous injection of placebo. Ten subjects received a liquid meal, 10 others received a solid meal. With the liquid meal, gastric emptying was measured 15 min after its ingestion and antral contraction was measured for 15 min by ultrasonography. With the solid meal, gastric emptying was measured both by ultrasonography (n=10) and by simultaneous scintigraphy (n=6), with antral contraction measured by ultrasonography for 5 h after ingestion of the meal.

Results and Conclusions: Octreotide given with a liquid or solid meal inhibited gastric emptying in healthy subjects. A significant suppression of antral contraction occurred only with a solid meal.
Review article: critical review of meta‐analyses of randomized clinical trials in hepatogastroenterology
Authors: AUPERIN A. , PIGNON J.‐P. , POYNARD T.
Published: October 2003

Background: This review attempts to identify meta‐analyses performed in hepatogastroenterology, and to assess their quality and to identify simple criteria of good quality.

Methods: Meta‐analyses of randomized clinical trials in hepatogastroenterology published as full papers before 1993 were included. A quality score was defined as the sum of 27 items evaluated in each publication and coded 2 if adequate, 1 if partial and 0 if missing. Quality criteria were identified by discriminant analysis through three groups of meta‐analyses defined by their quality score (poor, middle, high).

Results: From 1981 to 1992, 62 publications were identified, including 42% in the last 2 years. Nineteen per cent concerned peptic ulcers, 18% oesophageal varices and 6% digestive cancers. They reported 180 meta‐analyses. The quality score ranged from 14 to 40, the median was 29. Twenty‐five per cent of the studies obtained a score lower than 23 and 25% a score higher than 34. Several stages of meta‐analysis were poorly performed: identification and selection of trials, study of trial quality, data extraction and achievement of sensitivity analyses, subgroup and indirect analyses. Some of them led to biases and questions about the validity of results. Five criteria were significantly associated with high quality: presence of a protocol, assessment of trial quality, only randomized trials pooled, achievement of sensitivity analyses, and peer‐reviewed publication.

Conclusions: In hepatogastroenterology, there is an exponential increase in publication of meta‐analyses but their quality is heterogeneous. In particular, the control of the biases has to be better performed.
Randomized study comparing omeprazole plus amoxycillin versus omeprazole plus clarithromycin for eradication of Helicobacter pylori
Authors: SPINZI G. , BORTOLI A. , COLOMBO E. , LESINIGO E. , VENTURELLI R. , TERRUZZI V. , IMPERIALI G. , MINOLI G.
Published: October 2003

Background: Dual therapy with omeprazole plus amoxycillin or with omeprazole plus clarithromycin has been proposed for eradication of Helicobacter pylori. The main problem is the great variability in the rate of eradication.

Methods: A group of 287 consecutive patients with active peptic ulcers and H. pylori infections were admitted to a prospective, randomized, multicentre study, to be given omeprazole 20 mg b.d. plus either amoxycillin 1 g b.d. or clarithromycin 500 mg t.d.s. for 2 weeks. Cure was defined as the absence of H. pylori infection, 4–6 weeks after completing anti‐microbial therapy, assessed by urease activity and histology of antral and body gastric biopsies.

Results: The bacteria were eradicated in 68/143 patients (48%) treated with amoxycillin and omeprazole and 70/144 patients (49%) treated with clarithromycin and omeprazole (intention‐to‐treat analysis). The ulcers were healed in 118/127 patients (93%) treated with amoxycillin and in 115/123 (94%) of those treated with clarithromycin. Undesirable effects were rare with both treatments.

Conclusions: Combined treatment with omeprazole plus either amoxycillin or clarithromycin produced a high percentage of short‐term healing of ulcers and was well tolerated, but is not useful as first‐line anti‐Helicobacter pylori treatment.
Double‐blind study of the effect of cisapride on constipation and abdominal discomfort as components of the irritable bowel syndrome
Authors: SCHÜTZE K. , BRANDSTÄTTER G. , DRAGOSICS B. , JUDMAIER G. , HENTSCHEL E.
Published: October 2003

Aim: To study the effect of prokinetic treatment with cisapride in patients with constipation‐predominant irritable bowel syndrome.

Patients and methods: Ninety‐six patients were randomly assigned to treatment with either cisapride 5 mg three times daily or placebo three times daily for a period of 12 weeks. The dosage could be doubled after 4 weeks. Presence of the target symptoms abdominal pain, constipation and abdominal bloating was an obligatory criterion for inclusion in the study.

Results: After 12 weeks of treatment, 31%, 56% and 27% of the cisapride treated patients were found to be without the three target symptoms (P<0.05). The corresponding percentages for the placebo‐treated patients were 31%, 58% and 19%, respectively, (P<0.05). The visual analogue scale (VAS) symptom scores assessed by the patients for global rating of bowel disease, general well‐being and frequency of stool passage improved significantly within each treatment group (P<0.05). Evaluation of efficacy parameters using intention‐to‐treat analysis showed no statistically significant differences between the groups. Using efficacy analysis, the difficulty of stool passage showed a significantly higher improvement with cisapride (P0.05).

Conclusions: These results indicate that cisapride is not superior to placebo in the treatment of constipation and abdominal discomfort as components of irritable bowel syndrome. It may, hovever, be of use in improving the difficulty of stool passage.
Immediate repeat course of amoxycillin, metronidazole and omeprazole to eradicate Helicobacter pylori
Authors: STRÖM M. , SÖRBERG M. , JÖNSSON K.‐Å.
Published: October 2003

Aim: To investigate a repeat treatment regimen with the same antibiotic combination of amoxycillin and metronidazole in patients with continuing Helicobacter pylori infection.

Methods: Eighty‐two patients with severe peptic ulcer disease and concurrent Helicobacter pylori infection were treated with a two week regimen of omeprazole (40 mg once daily), amoxycillin (750 mg t.d.s.) and metronidazole (400 mg t.d.s.). Upper gastrointestinal tract endoscopy was performed before, and approximately 2 months after, completion of antibiotic therapy. Biopsies were taken for rapid urease testing and the histological demonstration of H. pylori infection. Patients with persistent H. pylori infection at follow‐up endoscopy were re‐treated with a second and identical antibiotic treatment course. A subsequent endoscopic examination with accompanying biopsies was performed at least 6 weeks after the second treatment course and after a further 6, 18 and 30 months.

Results: Eradication of H. pylori was achieved in 69 patients (84%, 95% CI: 75–90%) after the first treatment. Four patients (4/82=5%) were withdrawn from the study because of side‐effects. All of the remaining nine patients had their H. pylori infection eradicated after the second treatment course (95% CI: 70–100%). Seventy‐eight patients had a follow‐up examination after a median 30 months of the initial eradication of H. pylori, and all but one remained free of infection and none had an ulcer relapse.

Conclusions: This study demonstrates that patients with persistent H. pylori infection after completing a primary course of omeprazole (40 mg once daily), amoxycillin (750 mg t.d.s.) and metronidazole (400 mg t.d.s.) will probably respond to a repeat course of treatment with the same antibiotic combination.
Prescribing of nonsteroidal anti‐inflammatory drugs in general practice: determinants and consequences
Authors: HAWKEY C. J. , CULLEN D. J. E. , GREENWOOD D. C. , WILSON J. V. , LOGAN R. F. A.
Published: October 2003

Aim: To use Prescribing Analysis and Costs data to investigate factors associated with differences in rates of nonsteroidal anti‐inflammatory drug prescribing in Nottingham general practices.

Results: Poisson regression analysis revealed that the Age, Sex and Temporary Resident Prescribing Unit Index was the largest identifiable influence; larger practice size and a higher index of deprivation were also significantly associated with lower prescribing, whilst the number of partners was associated with higher levels of prescribing. However, even after correcting for the influence of age, sex and temporary residents, there was an 5.9‐fold variation in rates of prescribing. A similar Poisson regression analysis to identify factors associated with admission to hospital with ulcer bleeding in the elderly over the preceding 57 months identified the rate of nonsteroidal anti‐inflammatory drug (NSAID) prescribing as the only significant influence.

Conclusion: The data are compatible with 1 hospital admission per 2823 NSAID prescriptions (95% confidence intervals 2098–8110) and they emphasize the need for strategies to reduce levels of NSAID prescribing.
Review article: COX‐II inhibitors—a new generation of safer NSAIDs?
Authors: DONNELLY M. T. , HAWKEY C. J.
Published: October 2003

A hundred years after the introduction of aspirin as the first effective anti‐inflammatory drug, problems of tolerability still beset this class of drugs, in particular, gastrointestinal toxicity. Despite this, NSAIDs are among the most widely used and prescribed drugs world‐wide. Many agents have been used to counteract these side‐effects with varying degrees of success and acceptance.

Although the central mechanism of NSAID action, reduced prostaglandin production by cyclooxygenase (COX) inhibition, was first described 25 years ago, the recent discovery of a second, inducible form of cyclo‐oxygenase, COX‐2, has stimulated research and interest in producing NSAIDs that are inherently safer whilst maintaining efficacy.

Specific COX‐2 inhibitors, the first of which has recently been marketed in the UK, offer real hope as safer NSAIDs and this may be realised when drugs with even greater specificity become available. However, long‐term safety and efficacy need to be demonstrated in clinical practice, and questions remain unanswered about possible physiological roles for COX‐2.

Other approaches to improving the safety of NSAIDs, including profound acid suppression and nitric oxide donation, may prove to be as successful in this rapidly changing field.
One‐week triple therapy with omeprazole, amoxycillin and tinidazole for Helicobacter pylori infection: the significance of imidazole resistance
Authors: THIJS J. C. , VAN ZWET A. A. , THIJS W. J. , VAN DER WOUDEN E. J. , KOOY A.
Published: October 2003

Background: Triple therapy involving a proton pump inhibitor and two antibiotics has been suggested as an effective treatment for Helicobacter pylori infection. The impact of imidazole resistance on the efficacy of such regimens is largely unknown.

Methods: One hundred patients with culture proven H. pylori infection were treated with omeprazole 40 mg b.d., amoxycillin 1000 mg b.d., and tinidazole 500 mg b.d. for one week. Pre‐treatment imidazole susceptibility was measured by disk diffusion. Resistance was confirmed by E‐test. Eradication was assessed by endoscopy 6–8 weeks after the end of treatment. In cases of doubt a 13C‐urea breath test was performed. Side‐effects were scored using a semiquantitative scale.

Results: H. pylori was eradicated in 95% of the patients with an imidazole‐susceptible strain and in 69% of the patients with a resistant strain (P<0.005). Significant side‐effects were seen in 12%.

Conclusion: This proton pump inhibitor triple therapy is a simple, reasonably effective regimen with few significant side‐effects. The efficacy is dependent on the susceptibility of the infecting H. pylori strain.