bluuebunny/crossref_metadata_2025_split 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

BackgroundUlcerative 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.