摘要:

SUMMARYThe mechanisms underlying cell death are reviewed in order to propose new targets for the therapy of gastrointestinal disease. Necrosis is a set of precise biochemical and cellular lesions which culminate in cell destruction. A number of potential targets for drug therapy are discussed which will inhibit necrosis, including preservation of cellular ATP by inhibition of poly(ADP‐ribose) polymerase. Such therapies may be useful either as adjuncts to other therapeutic modalities such as immunosuppressive agents for the treatment of inflammatory conditions or on their own for organ preservation prior to organ transplantation. Either excessive apoptosis or failure of apoptosis plays an important role in a variety of gastrointestinal diseases. Failure of apoptosis is of particular importance in the development of colorectal cancer. Mutations or deletions ofp53, bcl‐2andmycprevents the appropriate deletion of malignant cells and causes resistance to anti‐cancer drugs which act by the induction of apoptosis. Correction of these genetic defects or replacement of their function is a major strategy in cancer prevention and therapy. It is concluded that manipulation of cell death processes is an important new area for gastrointestinal res

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00376.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYA role for prostaglandins in maintaining mucosal integrity in the gastrointestinal tract is well documented. While traditionally the effects of prostaglandins on mucosal blood flow and epithelial function have been regarded as critical in the mechanism of action of these fatty acids, recent evidence that mucosal ulceration is almost invariably associated with mucosal inflammation has caused a reevaluation of the role of prostaglandins in mucosal defence. This review focuses on the ability of prostaglandins to exert anti‐inflammatory, and therefore anti‐ulcerogenic, effects in the gastrointestinal tract. These effects of prostaglandins are attributable to their ability to suppress the release of inflammatory mediators and reactive oxygen metabolites from a number of immunocytes, stromal cells and inflammatory cells. There is emerging evidence for cooperative interactions between prostaglandins and nitric oxide in maintaining mucosal integrity. Recent work on the inducible isoform of prostaglandin synthase as it pertains to mucosal defence is also revie

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00377.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYOsteoporosis is a serious complication of inflammatory bowel disease which has not received adequate recognition despite its high prevalence and potentially devastating clinical effects. Its pathogenesis remains poorly defined although corticosteroid therapy and sex hormone deficiency are likely to play a major role.Recent advances in the diagnosis and management of osteoporosis have facilitated early detection of bone loss and identified means by which this may be prevented. Bone density measurements to predict fracture risk and define thresholds for prevention and treatment should be performed routinely in patients with inflammatory disease. Hormone replacement therapy is effective in prevention of bone loss in peri‐ and post‐menopausal patients, but the treatment of younger women and men of all ages requires further st

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00378.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYReflux of gastric acid and pepsins into the lower oesophagus causes symptoms such as heartburn and nausea, and tissue injury leading to erosive oesophagitis and stricture formation. This article reviews the mechanisms involved in protecting the oesophagus against acid‐mediated injury, including the role of the lower oesophageal sphincter, secondary oesophageal peristalsis and swallowed saliva. The oesophageal mucosa has inherent abilities to resist acid damage, and recent data from three laboratories suggest a secretory function with local production of bicarbonate and mucus responsive to local acidification. The evidence for these putative oesophageal defence mechanisms is discusse

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00379.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYThe search continues for a single reliable test of liver function that provides accurate prognostic information in chronic liver disease, in acute liver failure, and about graft function following orthotopic liver transplantation. Although transaminases, the commonly used markers of hepatocellular injury, have a high sensitivity in screening for liver disease, they do not provide any information about prognosis. Rational assessment of liver function using bilirubin, serum albumin and prothrombin‐time is limited by the relative lack of sensitivity of these measurements and their inability to identify the functional reserve of the liver. Dynamic liver function tests are an improvement on the static tests but are generally cumbersome.The ideal liver function test would be cheap, easy to perform and analyse, safe,havea simple pharmacokinetic profile with minimal drug interactions, have a high predictive value and provide quick results. Numerous quantitative liver function tests have been developed and have shown promise in some studies. The aim of this review is to assess the place of these tests in the practical management of liver diseas

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00380.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYAim: To perform a further Cox proportional hazards logistic regression analysis of data from two large‐scale placebo‐controlled trials with cisapride as maintenance treatment in reflux disease.Results: Analysis of each of the two databases, allowing the model to operate freely, led to the identification of a number of unexpected putative predictors of outcome in the 6 to 12 months following initial healing of oesophagitis with an H2‐receptor antagonist or omeprazole. This allowed us to delineate more accurately the patient population that is likely to respond to long‐term continuous treatment with low or standard dose cisapride.The analysis revealed that symptom severity may be more useful than endoscopic severity in predicting relapse or in guiding therapy. Reflux oesophagitis outcome is particularly poor in the presence of treatment‐recalcitrant symptoms or severe mucosal damage.Analysis showed cisapride to be effective in the maintenance treatment of patients with non‐refractory symptoms, irrespective of the initial severity of oesophagitis, the healing agent used, or a history of previous endoscop

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00381.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYBackground: Oesophagitis is usually a chronic condition. Healing with omeprazole is often followed by early relapse. Combination treatment and subsequent maintenance treatment with the prokinetic cisapride may be of benefit in relapse prevention.Methods: Patients with endoscopically proven oesophagitis, grade I (n= 120) or grade II (n= 105), were randomized in an open fashion to receive 8 weeks of healing treatment with omeprazole 20 mg daily (OM) followed by 12 months of follow‐up without maintenance treatment, or 8 weeks of combined treatment of omeprazole 20 mg daily plus cisapride 5 mg t.d.s. (OMCIS) followed by 12 months of maintenance treatment with cisapride 5 mg t.d.s. (CIS). Only the patients healed after acute treatment were included in the 12‐month follow‐up study for evaluation of endoscopic relapse.Results: In the group of patients with oesophagitis grade I (n= 58 receiving OM,n= 62 receiving OMCIS), healing rates were comparable for both acute treatment regimens. In the group of patients with grade II (n= 54 receiving OM,n= 51 receiving OMCIS), the healing rates were slightly but not significantly in favour of OMCIS after 4 and 8 weeks of treatment. During the 12 months of follow‐up, CIS maintenance treatment was associated with a significant reduction of relapse. In the group of patients with initial grade I oesophagitis, the relapse rates after 3 months were 20% in the OMCIS group receiving CIS maintenance treatment, compared to 48 % in the group healed on OM without further maintenance treatment (P= 0.04). After 6 months, these relapse rates were 31% and 85% respectively (P<0.001), and after 12 months 40% and 96% (P<0.001). In the group of patients with initial grade II oesophagitis, they were, respectively, 20% vs. 39% after 3 months (P= 0.056), 41% vs. 78% after 6 months (P<0.001) and 52% vs. 95 % after 12 months (P<0.001).Conclusions: The results of this open study indicate that continued treatment with cisapride 5 mg t.d.s. (after initial healing with omeprazole 20 mg daily plus cisapride 5 mg t.d.s.) is beneficial in the long‐term management of grade I and II oesophagitis : this treatment approach significantly reduces the high relapse rate observed after stopping healing treatment with o

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00382.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYBackground: The purpose of this study was to investigate if the use of a higher night time dose of ranitidine (300 mg) could keep significantly more duodenal ulcer patients in remission than the usual maintenance dose (150 mg).Methods: Double‐blind, multi‐centre, parallel group study of patients with proven healed duodenal ulcer randomized to ranitidine 150 mg or 300 mg daily for 1 year. The primary study end‐point was symptomatic, endoscopically proven ulcer relapse.Results: A total of 489 patients were recruited into the study. The endoscopically proven relapse rates were 6.1% of ranitidine 150 mg daily (n= 250) and 6.9% on 300 mg daily (n= 239). These differences were not statistically significant.Conclusion: This study provides further evidence that maintenance therapy with ranitidine 150 mg daily is highly effective at preventing duodenal ulcer relapse. The use of the higher dose of 300 mg daily does not appear to keep significantly more patients in remi

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00383.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYBackground: To summarize and quantify the evidence supporting rectal 5‐ or 4‐aminosalicylate (ASA) therapies for disease exacerbation or remission maintenance in distal ulcerative colitis, we performed a meta‐analysis.Methods: All randomized, double‐blind controlled trials involving aminosalicylate therapy were retrieved from a MEDLINE search, review articles on ulcerative colitis therapy or their bibliographies. Of 55 studies retrieved, 19 met the inclusion criteria. Appraisal and data extraction were performed by two observers and scoring disagreements were resolved by consensus.Results: Eleven trials tested 5‐ASA and three tested 4‐ASA in active ulcerative colitis. 5‐ASA was superior to placebo for inducing remission or symptomatic improvement in active ulcerative colitis with a pooled odds ratio of 7.36 (95% Confidence interval (CI): 4.72–11.47). In four trials the pooled odds ratio for endoscopic improvement was 10.04 (95 % CI: 5.72–17.61) and for histological improvement 10.31 (95% CI: 5.85–18.18). Studies evaluating 4–ASA suggest a benefit similar to prednisolone in treating active disease. Five trials assessed remission maintenance with 5‐ASA, and when compared to placebo gave a pooled odds ratio of 16.22 (95% CI: 4.71–55.92). No dose‐response relationship was observed. ASA compounds were not therapeutically superior to other treatments.Conclusions: We conclude that rectal 5‐ASA is effective therapy for active distal ulcerative colitis. More trials are needed to assess 4‐ASA, dose‐response effects and the ideal

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00384.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYAim: To assess the effects of FK506, a newly developed immunosuppressant, on experimental colitis in rats.Methods: Experimental colitis was induced by a single colonic instillation of hapten 2,4,6‐trinitrobenzene sulphonic acid (TNB) in anaesthetized rats. Rats received 30 mg TNB dissolved in 0.25 mL of 50% ethanol, and were sacrificed on day 5 following 4 days dosing with FK506 (0.25, 0.5, 1.0, 2.0 mg/kg, s.c.) or vehicle. Mucosal prostanoid concentrations were determined using high performance liquid chromotography. Tissue myeloperoxidase activities were measured. The effects of FK506 on superoxide radical formation by neutrophils in both rats and humans were also estimated in vitro.Results: Administration of FK506 significantly reduced the colonic damage in a dose‐dependent manner. Activities of myeloperoxidase and concentrations of 6‐keto‐prostaglandin Fl1α(6‐keto‐PGF1α, PGF2αand PGE2in colonic tissue increased significantly following induction of experimental colitis, however, FK506 did not affect these changes. FK506 reduced stimulant‐induced superoxide radical formation by neutrophils in rats and humans.Conclusion: FK506 decreased superoxide radical generation by neutrophils, which might contribute to the lessening of colonic dama

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00385.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY