Quality of life in Chinese patients with inflammatory bowel disease: validation of the Chinese translation of the Inflammatory Bowel Disease Questionnaire

BACKGROUND: Health-related quality of life is an important outcome measure in inflammatory bowel disease. The Inflammatory Bowel Disease Questionnaire is a quality of life questionnaire that has not been validated previously in Chinese patients with inflammatory bowel disease. AIM: To develop and validate a Chinese translation of the Inflammatory Bowel Disease Questionnaire, specifically determining its construct validity, discriminant ability, reliability and sensitivity to change. METHODS: We developed a Chinese version of the Inflammatory Bowel Disease Questionnaire. Chinese patients with Crohn's disease and ulcerative colitis completed the Chinese Inflammatory Bowel Disease Questionnaire and visual analogue scales measuring systemic, social, bowel and emotional well-being. Patients also completed a validated Chinese SF-36 generic quality of life questionnaire, the Crohn's disease activity index or the clinical activity index for ulcerative colitis. RESULTS: One hundred and thirty-five patients (59 with Crohn's disease and 76 with ulcerative colitis) were enrolled, 99 of whom also completed the Chinese Inflammatory Bowel Disease Questionnaire for a second time. The Chinese Inflammatory Bowel Disease Questionnaire correlated well with the SF-36 for all four domains (Spearman: r = 0.55-0.80), the Crohn's disease activity index (r = -0.62-0.72) and the clinical activity index for ulcerative colitis (r = -0.44-0.68), as well as with the visual analogue scales. The Chinese Inflammatory Bowel Disease Questionnaire accurately distinguished between active and inactive disease. Test-re-test reliability showed excellent intra-class correlation (0.76-0.92; all P < 0.001). The Chinese Inflammatory Bowel Disease Questionnaire was also sensitive to changes in disease activity (P < 0.05). CONCLUSION: The Chinese Inflammatory Bowel Disease Questionnaire is a valid and reliable test that correlates well with the patients' subjective well-being and clinical disease activity.     

Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: a prospective, comparative trial

BACKGROUND: In patients with inflammatory bowel disease, oral iron is anecdotally reported to be less effective and less well tolerated than in those without inflammatory bowel disease, and to increase disease activity. AIM: To study prospectively the effects of oral iron in patients with and without inflammatory bowel disease. METHODS: Patients with ulcerative colitis, Crohn's disease and non-inflammatory bowel disease controls, all with iron deficiency anaemia, were assessed with symptom diaries, a quality of life questionnaire (Inflammatory Bowel Disease Questionnaire; inflammatory bowel disease patients only) and blood tests to measure iron repletion, disease activity and antioxidant capacity before and after starting 4 weeks of oral iron. In patients with ulcerative colitis, sigmoidoscopic scoring and rectal biopsies for reactive oxygen metabolite production were performed before and after iron therapy. RESULTS: All groups showed increases in haemoglobin and ferritin. Iron intolerance occurred in about a quarter of patients in each group. Two of 33 (6%) of inflammatory bowel disease patients had a relapse during treatment. Symptoms worsened in ulcerative colitis, but not in Crohn's disease or non-inflammatory bowel disease patients; Inflammatory Bowel Disease Questionnaire scores improved in ulcerative colitis. Laboratory markers of disease activity, sigmoidoscopic scores, histological scores, antioxidant capacity levels and reactive oxygen metabolite production did not change. CONCLUSIONS: Oral iron is equally efficacious and well tolerated in inflammatory bowel disease and non-inflammatory bowel disease patients. A tiny minority of inflammatory bowel disease patients relapse in association with use of oral iron therapy.     

The efficacy of corticosteroid therapy in inflammatory bowel disease: analysis of a 5-year UK inception cohort

BACKGROUND: Corticosteroids remain the mainstay of first-line therapy in active inflammatory bowel disease. AIMS: To determine the clinical outcome after the first corticosteroid-therapy and to identify factors which predict response/failure. METHODS: 216 (136 ulcerative colitis and 80 Crohn's disease) patients were identified in this 5-year inception cohort. The outcomes of early (30 days) and late (1 year) responses were used. Multivariate analyses were performed to identify factors associated with outcome. RESULTS: 86 (63%) and 60 (75%) ulcerative colitis and Crohn's disease required corticosteroid therapy, respectively. In ulcerative colitis, at 30 days, 69 (51%), 42 (31%) and 25 (18%) patients demonstrated complete response, partial response and no response, respectively. For Crohn's disease, these outcomes were observed in 32 (40%), 28 (35%) and 20 (25%). After 1 year, 75 (55%), 23 (17%) and 29 (21%) patients with ulcerative colitis demonstrated prolonged response, corticosteroid-dependence or required surgery, respectively. For Crohn's disease, these outcomes were observed in 30 (38%), 19 (24%) and 27 (35%) patients. Extensive ulcerative colitis was a predictor of surgery (P = 0.001, OR: 15.2). In Crohn's disease, inflammatory disease behaviour was negatively associated with surgery (P = 0.02, OR: 0.13). CONCLUSION: Although corticosteroids are effective, dependence/resistance remains common. Patients with extensive ulcerative colitis and fistulizing/stricturing Crohn's are most at risk of failing corticosteroid therapy.     

The association of MYO9B gene in Italian patients with inflammatory bowel diseases

Background  Variants of myosin IXB ( MYO9B ) gene, encoding for a motor protein implicated in epithelial permeability, have been recently associated with inflammatory bowel disease.
Aims  To investigate the contribution of three polymorphisms of MYO9B gene for predisposition to Crohn's disease and ulcerative colitis, their association with clinical phenotypes, particularly intestinal permeability, and possible interaction with the CARD15 gene.
Methods  549 Crohn's disease patients, 658 ulcerative colitis patients and 674 controls were genotyped for the rs962917, rs1545620 and rs2305764 single nucleotide polymorphisms.
Results  Highly significant genotypic association with Crohn's disease and ulcerative colitis was shown for all three single nucleotide polymorphisms, with odds ratio ranging from 1.5 to 1.7 ( P -value: <0.01 to <0.002). A significant difference in allele frequencies was also observed in inflammatory bowel disease patients, with the single most significant association for rs1545620, detected in 47% of Crohn's disease, 47% of ulcerative colitis patients and 42% of controls ( P  < 0.005). No association with specific sub-phenotypes was found, with the exception of a trend towards an abnormal intestinal permeability ( P  = 0.043) in Crohn's disease carrying the rs1545620 risk allele.
Conclusions  Our findings confirm the association between the MYO9B polymorphisms and susceptibility to both ulcerative colitis and Crohn's disease, with a weak influence on sub-phenotypic expression.     

Glucose metabolism and insulin sensitivity in inactive inflammatory bowel disease

BACKGROUND: Inflammatory mediator concentration was found to be increased in active inflammatory bowel disease, and this could be related to an insulin-resistant state. Moreover, glucocorticoids, which are widely used in the treatment of inflammatory bowel disease, are notoriously related to insulin resistance. AIM: To measure body composition, whole body glucose uptake and oxidation in Crohn's disease and ulcerative colitis patients with inactive disease. METHODS: All patients had clinical, ultrasound and biochemical assessment. Body composition was determined by isotopic dilution technique; basal metabolic rate and substrate oxidation were measured by indirect calorimetry. Insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp. Ten patients with inactive Crohn's disease (five males, aged 31.1 +/- 7.0 years) and 10 patients with inactive ulcerative colitis (five males, aged 33.4 +/- 8.8 years) participated in the study. Forty healthy subjects, matched for age and height were used as a control group. RESULTS: Crohn's disease patients showed lower BMI (P < 0.001), fat mass (P < 0.05) and respiratory quotient (P < 0.001) values compared to both ulcerative colitis and control subjects. No difference in peripheral glucose uptake (micromol/kg/min) was found between groups (respectively 42.5 +/- 6.78 in Crohn's disease, 40.2 +/- 8.00 in ulcerative colitis and 41.4 +/- 10.8 in control subjects). Glucose storage and oxidation did not differ between groups. CONCLUSION: Our data showed that inflammatory bowel disease patients in a remission phase of the disease activity had a whole body glucose uptake and oxidation similar to those of control subjects, probably due to fat-free mass preservation and low blood and tissue cytokine concentration.     

Age at onset of inflammatory bowel disease and the risk of surgery for non-neoplastic bowel disease

BACKGROUND: There is conflicting data regarding the response to medical and surgical therapy for inflammatory bowel disease with respect to age at disease onset. AIM: To determine if the age at onset of Crohn's disease and ulcerative colitis is a risk factor for surgery for non-neoplastic bowel disease. METHODS: This was a case-control study of patients evaluated between 1998 and 2001. Cases had undergone an initial operation for bowel disease. Controls were matched 1:1 for gender, disease subtype, date of first visit (+/-2 years), time from diagnosis prior to first visit (+/-3 years) and duration of follow-up. Association with age, disease extent, smoking history, medication use and co-morbidities vs. case/control status was assessed using multiple variable conditional logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (CI) for undergoing surgery. RESULTS: Among 132 Crohn's patients, older patients had lower odds for surgery (OR per 5 years, 0.86; 95% CI: 0.75-0.98). The rate of surgery for non-neoplastic bowel disease was not significantly associated with disease distribution, co-morbidities or cigarette smoking. Among 234 ulcerative colitis patients, the rate of surgery was unrelated to age, disease extent, co-morbidities or cigarette smoking, CONCLUSIONS: For Crohn's disease, but not ulcerative colitis, the risk of surgery for non-neoplastic bowel disease decreases with increasing age at diagnosis, irrespective of disease distribution and history of cigarette smoking.     

Quality of life in patients with established inflammatory bowel disease: a UK general practice survey

BACKGROUND: The current understanding of quality of life impairment in inflammatory bowel disease has largely been derived from selected populations and may not reflect the experience of patients in the community, where fewer than half are likely to be under specialist care. AIM: To describe the health-related quality of life in a community-based sample of patients with established inflammatory bowel disease and explore its association with the type and extent of disease, gender, age, material deprivation and other factors. METHODS: Adults with established inflammatory bowel disease were identified systematically from the records of 23 family practices in north-east England. The health-related quality of life was assessed by self-completion of the UK Inflammatory Bowel Disease Questionnaire. RESULTS: Five hundred and fifty-six patients were sent the questionnaire and 409 (74%) gave usable replies. Lower scores (worse quality of life) were significantly associated with female gender, Crohn's disease, more extensive disease (ulcerative colitis) and being under specialist care. The mean health-related quality of life score was significantly lower in patients resident in more deprived districts, independent of the type and extent of disease. CONCLUSIONS: Most patients with established inflammatory bowel disease showed only minor impairment of their health-related quality of life. On average, women and those with Crohn's disease were relatively more affected. Clinicians responsible for the care of patients with inflammatory bowel disease should be aware of these more vulnerable groups.     

Finger clubbing in inflammatory bowel disease: its prevalence and pathogenesis

Finger clubbing, measured objectively by using the hyponychial angle, was present in 75 out of 200 (38%) patients with Crohn's disease, 15 out of 103 (15%) with ulcerative colitis, and two out of 24 (8%) with proctitis. In Crohn's disease and ulcerative colitis the hyponychial angle was significantly correlated with both disease activity and the extent of fibrosis in the resected specimens from 47 surgically treated patients. The prevalence of finger clubbing in patients with macroscopic disease within the area of the gut innervated by the vagus nerve was significantly higher than that in patients in whom the disease was confined to the distal colon and rectum. Finger clubbing in patients with Crohn's disease tended to regress after resection of macroscopic disease. It is concluded that finger clubbing is significantly commoner in Crohn's disease than ulcerative colitis. The focal stimuli for finger clubbing include mucosal inflammatory change and fibrosis mediated by the vagus and possibly other autonomic pathways acting as the afferent arc of a finger-clubbing reflex.     

The serum concentrations of zinc, copper and selenium in children with inflammatory bowel disease

OBJECTIVE: To estimate the levels of trace elements in children with inflammatory bowel disease (IBD). DESIGN: Prospective cross sectional study. SETTING: Gastroentrology Unit, Great Ormond Street Children's Hospital, London, UK. SUBJECTS: Seventy four children with inflammatory bowel disease confirmed endoscopically and histologically (38 ulcerative colitis and 36 Crohn's disease) and 40 age matched controls had their serum zinc, copper and selenium assayed at presentation. MAIN OUTCOME MEASURE: Serum levels of zinc, copper and selenium in children with inflammatory bowel disease and age matched controls. RESULTS: Seventy four children with inflammatory bowel disease confirmed endoscopically and histologically (38 ulcerative colitis and 36 Crohn's disease) and 40 age matched controls had their serum zinc, copper and selenium assayed at presentation. The serum levels of selenium were significantly lower in cases of ulcerative colitis 0.63 +/- 0.25 mmol/L and Crohn's disease 0.69 +/- 0.25 mmol/L than in the controls 0.84 +/- 0.13 mmol/L (p < 0.01). The serum copper concentration was significantly higher in those with Crohn's disease 22.7 +/- 5.49 mmol/L than in those with ulcerative colitis 17.6 +/- 5.15 mmol/L and the controls 20.76 +/- 4.06 mmol/L (p < 0.01). Children with Crohn's disease had a lower serum zinc level 11.01 +/- 2.49 mmol/L compared to the control level of 13.6 +/- 1.63 mmol/L (p < 0.05), but the levels were not significantly different in the controls and ulcerative colitis (p > 0.10). Children with inflammatory bowel disease have abnormal levels of the trace elements which is more marked in those with Crohn's disease. CONCLUSION: Children with IBD in this study show abnormalities of the trace elements which is probably a result of inadequate intake, reduced absorption, increased intestinal loss due to impairment of the absorption as a result of the inflammatory process. The reduced free radical scavenging action of zinc and selenium as a result of their deficiency may contribute to the continued inflammatory process of IBD. The recommendation of the supplementation of these trace elements in IBD is further supported by the findings of this study in children.     

Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study

BACKGROUND: Uncontrolled studies suggest that granulocyteaphaeresis might be useful in the management of active ulcerative colitis. AIM: To assess the efficacy of granulocyteaphaeresis treatment in active steroid-dependent inflammatory bowel disease. METHODS: We conducted a multicentre, prospective, open, pilot study in patients with steroid-dependent inflammatory bowel disease. All patients were started on 60 mg/day of prednisone; after 1 week, a five-session programme of granulocyteaphaeresis (once per week) was started. The steroid dose was tapered weekly if there was clinical improvement. Remission was defined as an inactive clinical activity index together with complete withdrawal of steroids at week 6. The patients were followed up for at least 6 months or until disease relapse. RESULTS: Twenty-six patients (14 ulcerative colitis, 12 Crohn's disease) were included. More than a half had been previously treated with immunomodulators. Remission was achieved in 62 and 70% of ulcerative colitis and Crohn's disease, respectively. During a median follow-up of 12.6 months, six of eight ulcerative colitis patients maintained their clinical remission; however, only one Crohn's disease patient remained in remission after the first 6 months of follow-up. CONCLUSIONS: Granulocyteaphaeresis is a safe treatment option in inflammatory bowel disease. A five-session programme of granulocyteaphaeresis seems to be efficient in the treatment of steroid-dependent ulcerative colitis, but not in Crohn's disease.     

Anti-Saccharomyces cerevisiae mannan antibodies in inflammatory bowel disease: comparison of different assays and correlation with clinical features

BACKGROUND: Anti-Saccharomyces cerevisiae mannan antibodies have been proposed as a new serological marker associated with Crohn's disease. However, their clinical value is still unclear; furthermore, a standardization of anti-S. cerevisiae mannan measurements is lacking. AIM: In this study, we aimed to assess the correlation between anti-S. cerevisiae mannan detection and specific clinical features in Crohn's disease and ulcerative colitis. Moreover, we tested the concordance of four different anti-S. cerevisiae mannan assays. MATERIALS AND METHODS: Serum samples from 196 patients with Crohn's disease, 197 patients with ulcerative colitis and 100 unrelated healthy controls were tested for anti-S. cerevisiae mannan with a standard enzyme-linked immunosorbent assay method (Lille) by one of the authors (VP). Subsequently, 60 randomly selected serum samples (27 Crohn's disease, 28 ulcerative colitis and five healthy controls) were tested for anti-S. cerevisiae mannan with three different commercial kits. RESULTS: With the Lille assay, anti-S. cerevisiae mannan were detected in 100 of 196 patients with Crohn's disease (51%; P < 0.0001 vs. controls), 32 of 197 patients with ulcerative colitis (16%; P < 0.02 vs. controls), and six of 100 controls (6%). No correlation between presence of anti-S. cerevisiae mannan and specific clinical features was found in both ulcerative colitis and Crohn's disease patients. The percentages of anti-S. cerevisiae mannan detected with four different assays ranged from 28 (Bouty) up to 43% (Inova), but these differences did not reach statistical significance. The concordance rate of anti-S. cerevisiae mannan detection in the four assays was very low (11 concordant results of 60 samples, 18.3%) (k = 0.15). No improvement of the concordance rate was obtained by modifying the suggested cut-off values (k = 0.20). CONCLUSION: In this study, we confirm that anti-S. cerevisiae mannan are significantly more frequent in Crohn's disease patients compared with ulcerative colitis patients (P < 0.0001) and controls. However, no correlation with clinical features was found in both ulcerative colitis and Crohn's disease. The low prevalence of anti-S. cerevisiae mannan, at least in our population, and the low concordance rate between different assays, makes the clinical role of this marker questionable.     

Anti-TNF alpha therapy in the management of extraintestinal manifestation of inflammatory bowel disease

Inflammatory bowel disease, Crohn's disease and ulcerative colitis, are immune-mediated disorders of unknown etiology that primarily affect the gastrointestinal tract. In addition, other organ systems can be involved such as joint/bones, skin, eyes, hepatobiliary tract, lungs and kidney. Overall, they represent extraintestinal manifestations of inflammatory bowel disease and may present before, in conjunction or after the onset of bowel disease. Extraintestinal manifestations are observed in 20-40% of patients and frequently have a negative impact on quality of patients' life. Some extraintestinal manifestations such as arthritis, erytema nodosum, pyoderma gangrenosum, iritis, uveitis have a pathogenic tumor necrosis factor alpha-dependent mechanism common with Crohn's disease and ulcerative colitis. Early recognition and treatment of extraintestinal manifestations can minimize potential severe complications. In this review we provide an overview on the prevalence and clinical aspects of the more commonly reported extraintestinal manifestations of Crohn's disease and ulcerative colitis and the role of tumor necrosis factor alpha inhibitors in their treatment.     

The quality of life in patients with Crohn's disease

BACKGROUND: Health-related quality of life studies provide insight into the influence of Crohn's disease on patients' lives, and the potential impact on professional and personal productivity. AIM: To compare health-related quality of life in Crohn's disease patients with that in other patients and healthy controls, and between medically and surgically treated Crohn's disease patients, and to correlate health-related quality of life with Crohn's disease activity. METHODS: An expanded MEDLINE search of full length, English language, adult Crohn's disease studies from January 1966 to September 2000 was performed. The key words utilized were: 'Quality of Life', 'Health Status' or 'Health Related Quality of Life' and 'Crohn's' or 'Inflammatory Bowel Disease'. RESULTS: A total of 258 articles were identified; 236 subsequently were excluded, leaving 22 for analysis. Compared with Crohn's disease patients, the health-related quality of life was better in healthy controls and in ulcerative colitis patients (except pre-colectomy), but similar to or worse than that in many other medical conditions. The health-related quality of life was directly correlated with Crohn's disease activity, and was worse in active disease than in remission. The health-related quality of life was improved only in the short term in surgically vs. medically treated Crohn's disease patients. CONCLUSIONS: Health-related quality of life analysis provides important insights into the impact of Crohn's disease, and should be included in clinical trials. Researchers, clinicians and other health care providers need to be cognizant of the impact of the health-related quality of life upon patients' lives.     

A history of immunosuppressive drugs in the treatment of inflammatory bowel disease: origins at The Mount Sinai Hospital

Much of what we know about the role of immunopathologic mechanisms in causing Crohn's disease and ulcerative colitis originated from research at The Mount Sinai Hospital. The authors were privileged to have been able to share in this undertaking, along with many others, including Moschcowitz, Klemperer, Otani, Crohn, Ginzburg, Oppenheimer, Garlock, Lyons, Marshak, Janowitz, Aufses, Waye, Greenstein, Sachar, Meyers, Gelernt, Mayer, Lichtiger and Kornbluth. In medical history, elucidation of disease processes is often serendipitous. Transplant surgery was successful because of the discovery by Hitchings and Elion of 6-mercaptopurine (6-MP) and azathioprine, which inhibited rejection. And the concept of immunosuppression slowly evolved into possible treatment of any disease thought to be caused by autoimmunity. This includes those diseases of the bowel seen so frequently at The Mount Sinai Hospital: ileitis, granulomatous colitis, ileocolitis, and ulcerative colitis. This paper depicts the progressive role of immunosuppressive drugs, from corticosteroids to 6-mercaptopurine, cyclosporine and anti-tumor necrosis factor, in both the treatment and understanding of the pathogenesis of Crohn's disease and ulcerative colitis. Major contributions to these treatments have come from physicians and surgeons with roots at The Mount Sinai Hospital.     

Review article: insurance risks for patients with ulcerative colitis or Crohn's disease

Prospective population-based studies have allowed a re-evaluation of the risks of insuring patients with ulcerative colitis or Crohn's disease. Life expectancy, the risk of cancer and working capacity are very much better than previously recognised and are normal for many patients. Three population-based studies in ulcerative colitis have shown a mortality similar to or slightly less than the general population except in the first year after diagnosis, whilst two have shown a slightly higher mortality (standardized mortality ratio, SMR=1.4), except for those with proctitis. In Crohn's disease, two population-based studies have also shown an increased mortality (SMR=1.4), which is similar to that of unskilled manual labourers (SMR=1.43) from all causes of death. Three other studies have shown no increase in overall mortality, except in the first 5 years after diagnosis, in those with proximal small intestinal disease and in some patients needing multiple operations. Insurance risks should be evaluated on an individual basis, after details of the extent and pattern of disease have been obtained. Although the 'standard life' in insurance terms differs from that of the general population, because people who seek life assurance are self-selected from a more affluent section of society, many patients can be identified who have a particularly good prognosis. These include patients with ulcerative proctitis, those with left-sided colitis in extended remission (>12 months), and patients more than 30 years old with localized ileal or ileocaecal Crohn's disease that has responded to treatment. From the published data, it is difficult to justify increasing the insurance premium in such patients.     

Effects of iron and iron chelation in vitro on mucosal oxidant activity in ulcerative colitis

BACKGROUND: Reactive oxygen species may be pathogenic in ulcerative colitis. Oral iron supplements anecdotally exacerbate inflammatory bowel disease and iron levels are elevated in the inflamed mucosa. Mucosal iron may enhance hydroxyl ion production via Fenton chemistry. Conversely, the iron chelator, desferrioxamine, is reportedly beneficial in Crohn's disease. AIMS: To assess the in vitro effects of exogenous iron and of iron chelators on the production of reactive oxygen species by colonic biopsies from normal control subjects and patients with ulcerative colitis. METHODS: Luminol-amplified chemiluminescence was used to measure mucosal reactive oxygen species production both before and after addition in vitro of ferric citrate (100 microM), desferrioxamine (1 mM) and 1,10-phenanthroline (1 mM). RESULTS: Ferric citrate had no effect on the chemiluminescence produced by human colonic mucosa. However, desferrioxamine and phenanthroline reduced chemiluminescence by 47% (n=7, P=0.018) and by 26% (n=10, P=0.005), respectively, in inactive ulcerative colitis, and by 44% (n=9, P=0. 008) and 42% (n=11, P=0.006) in active disease. CONCLUSION: The lack of effect of ferric citrate suggests that sufficient free iron is already present in inflamed biopsies to drive the Fenton reaction maximally. The effects of desferrioxamine and 1,10-phenanthroline on the chemiluminescence of biopsies from patients with ulcerative colitis suggest that a clinical trial of topical iron chelation in active disease is indicated.     

NOD2/CARD15 gene polymorphisms and Crohn's disease in the Chinese population

BACKGROUND: Crohn's disease affects people world-wide, but the incidence in Asia is lower than in Western countries. This difference may be due to genetic and/or environmental factors. Three single nucleotide polymorphisms (SNPs) of the NOD2/CARD15 gene have been identified to be independently associated with the development of Crohn's disease in Caucasians. Whether these SNPs are involved in the pathogenesis of Crohn's disease in the Chinese population is unknown. AIM: To determine if NOD2/CARD15 gene polymorphisms are found in Chinese patients with Crohn's disease. METHODS: Sixty-five consecutive Chinese Crohn's disease patients had genotyping performed using sequence-specific PCR directed against the wild-type and the Arg702Trp, Gly908Arg and 3020insC variants of the NOD2/CARD15 gene. Controls consisted of 63 patients with ulcerative colitis and 70 patients with dyspepsia. RESULTS: None of the patients with Crohn's disease had heterozygous or homozygous SNP variants. Similarly none of the ulcerative colitis or dyspeptic controls had these SNPs. CONCLUSION: The three previously described SNPs associated with the development of Crohn's disease in Caucasians are not found in Chinese patients with Crohn's disease.     

The efficacy of methotrexate for maintaining remission in inflammatory bowel disease

BACKGROUND: The management of patients with inflammatory bowel disease who are resistant to or intolerant of azathioprine remains a challenge. Low-dose methotrexate has been shown to be effective in inducing remission in Crohn's disease. AIM: This review was conducted because there are limited long-term follow-up data during and after stopping treatment. There are also limited data on the use of methotrexate in ulcerative colitis. METHODS: The study was a retrospective review of clinical notes. Remission was defined as minimal bowel symptoms without the need for oral steroids for 3 months. Relapse was defined as bowel symptoms that required steroid treatment or surgery. RESULTS: Seventy patients were reviewed; 48 had Crohn's disease and 22 had ulcerative colitis. The mean duration of treatment was 17.1 months; the mean maintenance dose was 20 mg weekly. Remission was achieved in 34 of 55 patients who completed more than 3 months of treatment (62%). Life-table analysis showed that the chances of remaining in remission at 12, 24 and 36 months (if treatment was continued) were 90%, 73% and 51%, respectively. The chances of remaining in remission after stopping treatment at 6, 12 and 18 months were 42%, 21% and 16%, respectively. The dose of methotrexate (mg/kg) was associated with the induction of remission (P=0.02). Treatment was equally effective for Crohn's disease and ulcerative colitis. CONCLUSIONS: Maintenance methotrexate treatment gives acceptable remission rates for treatment periods up to 3 years. After stopping treatment, relapse is frequent and occurs early (usually within 1 year).     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

Patients with refractory Crohn's disease or ulcerative colitis respond to dehydroepiandrosterone: a pilot study

BACKGROUND: Dehydroepiandrosterone is a steroid hormone used as an 'over-the-counter' drug in the USA. Treatment with dehydroepiandrosterone was effective in randomized controlled trials in patients with systemic lupus erythematosus. Dehydroepiandrosterone sulphate concentrations are decreased in patients with inflammatory bowel disease. Dehydroepiandrosterone inhibits nuclear factor-kappaB and the secretion of interleukin-6 and interleukin-12 via the peroxisome proliferator-activated receptor alpha. AIM: A phase II pilot trial was started to evaluate the effect of dehydroepiandrosterone in active inflammatory bowel disease. METHODS: Twenty patients with chronic active inflammatory bowel disease [seven Crohn's disease (Crohn's disease activity index, 242 +/- 51; mean +/- s.d.); 13 ulcerative colitis (clinical activity index, 7.8 +/- 2.1)] took 200 mg dehydroepiandrosterone per day orally for 56 days. RESULTS: Six of the seven patients with Crohn's disease and eight of the 13 patients with ulcerative colitis responded to treatment, with a decrease in the Crohn's disease activity index of > 70 points and a decrease in the clinical activity index of > 4 points, respectively. Six Crohn's disease patients and six ulcerative colitis patients went into remission (Crohn's disease activity index < 150; clinical activity index 相似文献