Background and aim: There are limited evidence based data concerning the use of azathioprine in ulcerative colitis. We aimed to compare the efficacy of azathioprine and oral 5-aminosalicylic acid in inducing remission of steroid dependent ulcerative colitis. Methods: Seventy two patients with steroid dependent ulcerative colitis were admitted to this investigatorblind study. Steroid dependence was defined as a requirement for steroid therapy >10 mg/day during the preceding six months, with at least two attempts to discontinue the medication. The disease had to be clinically and endoscopically active at study entry, and all patients were taking systemic prednisolone (40 mg/day). Patients were randomised to receive azathioprine 2 mg/kg/day or oral 5-aminosalicylic acid 3.2 g/day, for a six month follow up period. The outcome of the treatment was defined as (1) success, indicating induction of clinical and endoscopic remission and steroid discontinuation, or (2) failure, indicating the absence of clinical and endoscopic remission and therefore the need for at least one further cycle of systemic steroids to control symptoms, apart from the initial one, or colectomy. Results: Significantly more patients in the azathioprine than in the 5-aminosalicylic acid group had clinical and endoscopic remission, and discontinued steroid therapy, both in the intention to treat (azathioprine v 5-aminosalicylic acid: 19/36 patients (53%) v 7/36 (21%); odds ratio (OR) 4.78 (95% confidence interval (CI) 1.57-14.5)) and per protocol (azathioprine v 5-aminosalicylic acid: 19/33 patients (58%) v 7/34 (21%); OR 5.26 (95% CI 1.59-18.1)) analysis. Conclusions: Azathioprine is significantly more effective than 5-aminosalicylic acid in inducing clinical and endoscopic remission and avoiding steroid requirement in the treatment of steroid dependent ulcerative colitis.

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Despite all of the advances in our understanding of the pathophysiology of inflammatory bowel disease (IBD), we still do not know its cause. Some of the most recently available data are discussed in this review; however, this field is changing rapidly and it is increasingly becoming accepted that immunogenetics play an important role in the predisposition, modulation and perpetuation of IBD. The role of intestinal milieu, and enteric flora in particular, appears to be of greater significance than previously thought. This complex interplay of genetic, microbial and environmental factors culminates in a sustained activation of the mucosal immune and non-immune response, probably facilitated by defects in the intestinal epithelial barrier and mucosal immune system, resulting in active inflammation and tissue destruction. Under normal situations, the intestinal mucosa is in a state of 'controlled' inflammation regulated by a delicate balance of proinflammatory (tumour necrosis factor [TNF]-alpha, interferon [IFN]-gamma, interleukin [IL]-1, IL-6, IL-12) and anti-inflammatory cytokines (IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may, therefore, be a logical target for IBD therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, T-helper cell (T(h))-1 polarisation, T-cell activation or nuclear factor (NF)-kappaB, and other miscellaneous therapies are being evaluated as potential therapies for IBD. In this context, infliximab is currently the only biologic agent approved for the treatment of inflammatory and fistulising Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP 571, certolizumab pegol (CDP 870), etanercept, onercept and adalimumab. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanisms involved in the inflammatory process. Lymphocyte-endothelial interactions mediated by adhesion molecules are important in leukocyte migration and recruitment to sites of inflammation, and selective blockade of these adhesion molecules is a novel and promising strategy to treat Crohn's disease. Therapeutic agents that inhibit leukocyte trafficking include natalizumab, MLN-02 and alicaforsen (ISIS 2302). Other agents being investigated for the treatment of Crohn's disease include inhibitors of T-cell activation, peroxisome proliferator-activated receptors, proinflammatory cytokine receptors and T(h)1 polarisation, and growth hormone and growth factors. Agents being investigated for treatment of ulcerative colitis include many of those mentioned for Crohn's disease. More controlled clinical trials are currently being conducted, exploring the safety and efficacy of old and new biologic agents, and the search certainly will open new and exciting perspectives on the development of therapies for IBD.

Abstract. Ardizzone S, Bollani S, Bettica P, Bevilacqua M, Molteni P, Bianchi Porro G (`L. Sacco' University-Hospital, Milan, Italy). Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn's disease and ulcerative colitis. J Intern Med 2000; 247: 63±70.Objectives. The aims of this study were to assess bone metabolism in inflammatory bowel disease (IBD) patients and to evaluate potential differences between Crohn's disease (CD) and ulcerative colitis (UC) with respect to the mechanisms underlying bone loss in this group of diseases. Design and setting. This was a cross-sectional study which started in 1992. Patients were randomly selected for invitation to participate and were examined during the years 1992±95 in one research clinic in Milan. Subjects and methods. Fifty-one patients suffering from CD (30 women and 21 men, mean age 38.7 6 13.2 years) and 40 with UC (15 women and 25 men, mean age 34.4. 6 12.5 years) entered the study. Thirty healthy subjects were selected as sex-and age-matched controls (C). Spine and femoral neck bone mineral density (expressed as T score), calciotropic hormones (parathyroid hormone, PTH; 25-hydroxycholecalciferol, 25(OH)D 3 ; 1,25-hydroxycholecalciferol, 1,25(OH)D 3 ) and biochemical markers of bone turnover (ostecalcin, OC; total alkaline phosphatase, ALP; type I collagen Cterminal telopeptide, ICTP) were evaluated. Results. Spine and femur T scores were similar in the two groups (spine: CD = ±1.49 6 1.46; UC = ± 1.67 6 1.13; femur: CD = ±1.80 6 1.36; UC = ± 1.60 6 1.03). Based upon the WHO guidelines, only 8% of CD patients and 15% of UC patients had a normal bone mineral density (BMD), 55% (CD) and 67% (UC) were osteopenic, and 37% (CD) and 18% (UC) were osteoporotic. The distribution amongst the three different diagnostic groups was not significantly different between CD and UC groups (P = 0.11). PTH and 25(OH)D 3 concentrations were not significantly different between CD and UC patients and controls, whilst 1,25(OH)D 3 concentrations were significantly lower in both CD and UC patients compared with controls (P , 0.05). Bone turnover was increased in UC but not in CD patients, as shown by significantly increased concentrations in UC patients of both OC (CD = 7.77 6 5.06, UC = 10.03 6 6.24, C = 6.58 6 2.87, P , 0.05 vs.C) and ICTP (CD = 5.74 6 3.94, UC = 10.2 6 8.47, C = 3.48 6 0.95, P , 0.05 vs. CD and C). In a stepwise regression that included age, sex, disease duration and cumulative prednisolone dose as independent variables, the femur T score was significantly inversely related to disease duration (r 2 = 0.125, F = 6.06) in CD patients. In UC patients, the spine T score was inversely related to age (r 2 = 0.107, F = 5.49) and significantly related to sex (more negative in males: r 2 = 0.3, F = 16.1); the femur T score was significantly related to sex (more negative in males) and inversely related to the cumulative prednisolone dose (r 2 = 0.283, F = 7.3). Conclusions. These data show that IBD patients have a diffuse osteopenia, the degr...

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SUMMARYBackground: Although bowel ultrasound is a widely accepted diagnostic tool in bowel diseases, its value as the primary imaging procedure in patients with symptoms/signs suggestive of inflammatory bowel disorders is still unclear. Aim: To investigate the accuracy of bowel ultrasound compared with barium X-ray studies, computed tomography, endoscopy and bowel surgery in the initial assessment of inflammatory bowel disorders. Methods: Four hundred and eighty-seven patients hospitalized consecutively for symptoms or signs suggestive of a bowel disorder between December 1999 and March 2002 were initially enrolled in the study. All patients underwent bowel ultrasound as the first imaging procedure within 36 h of admission; radiographic evaluations, endoscopy and/or surgery were then performed as appropriate and the results of these investigations were used as the gold standard. Results: Three hundred and thirty-six patients had pathological findings of the bowel detectable at

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