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Objective To evaluate the effect and mechanism of 5-aminosalicylic acid (5-ASA) on bone marrow suppression caused by thiopurines, and to explore the proper dosage of thiopurines when combined with 5-ASA for inflammatory bowel diseases (IBD) patients.MethodsThe clinical data of IBD patients who took thiopurines were retrospectively analyzed. Thiopurine methyltransferase (TPMT) activity and 6-thioguanine nucleotide (6-TGN) concentration were tested.In prospective study, patients firstly treated with azathioprine (AZA) of 50 mg/d for 4 weeks, then combined with 5-ASA of 3 g/d for another 4 weeks.The concentration of 6-TGN in red blood cells (RBC) was analyzed at the end of 4th and 8th week.Results In retrospective study, there were 45 cases in AZA/6-mercaptopurine (MP) combined with 5-ASA group, 94 patients were in AZA/6-MP.alone group.The incidence of bone marrow suppression in these two groups were 46.7％ and 16.0％, respectively.Multivariates regression analysis indicated co-administration of 5-ASA was the only risk factor of increasing bone marrow suppression incidence (OR=3.45,95％ CI 1.31 ～ 9.04).There was no significant difference of TPMT activity between AZA/6-MP combined with 5-ASA group and AZA/6-MP alone group(t=-0.351 ,P=0.734).The 6-TGN concentration was significantly higher in AZA/6-MP combined with 5-ASA group than that of AZA/6-MP alone group (the median concentration was 384.9 pmol/8× 108 RBC and 286.4 pmol/8× 108 RBC,F=29.15,P=0.00).Prospective study was completed in 8 patients.After treated with AZA of 50 mg/d for 4 weeks, the 6-TGN concentration of 7 patients was lower than 230 pmol/8 × 108 RBC.After added with 5-ASA of 3 g/d for another 4weeks, the 6-TGN concentration of 7 patients was over 230 pmol/8 × 108 RBC, three patients of those was even higher than 420 pmol/8 × 108 RBC, and bone marrow suppression occurred in 2 patients.ConclusionsThe incidence of bone marrow suppression increased in Chinese IBD patients treated with recommended routine dossage of AZA/6-MP when conbined with 5-ASA.The mechanism may be related with the increased concentration of 6-TGN in RBC.To reduce the AZA dosage may possibly keep the efficacy while decrease the incidence of bone marrow suppression.
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Objective To study the correlation of fecal calprotectin and lactoferrin with intestinal mucosa lesions in Crohn′s disease (CD). Methods Eighty-eight cases of diagnosed CD patients were selected as study group and 35 irritable bowel syndrome (IBS) patients were as controls. Fecal samples of CD patients were collected in one week before colonoscopy examination and of IBS patients were collected of CD patients, CD activity index (CDAI) was calculated at same visit, and CD endoscopic index (CDEI) was calculated in the subsequent endoscopic examination. The level of fecal calprotectin and lactoferrin were tested by ELISA method. Results The median levels of facal calprotectin and lactoferrin in CD patients were 277.16 mg/kg (from 96.85 to 693.57 mg/kg) and 59.68 mg/kg (from 10.75 to 100.58 mg/kg) respectively, which were significantly higher than those of IBS patients (7.6mg/kg, from 5.54 to 32.3 mg/kg and 0.65 mg/kg from 0.23 to 4.34 mg/kg), (Z=-8.301 and -7.986, respectively both P =0.000). There were no significant difference of calprotectin and lactoferrin level between CD patients with colon pathological changes and without colon pathological changes (Z=-0.424 and -0.699,P=0.672 and 0.485, respectively). There was no significant difference of calprotectin and lacoferrin level between remission and active periods in CD patients (Z=-1.491 and -1.075, P=0.136 and 0.283, respectively). The median values of calprotectin and lactoferrin of patients in moderate and severe active period judged under endoscopy were 663.11 mg/kg (from 263.45 to 2015.63 mg/kg) and 105.64 mg/kg (from 56.52 to 187.44) mg/kg respectively, in mild active period were 344.54 mg/kg (from 132.03 to 722.67 mg/kg) and 86.68 mg/kg (from 21.07 to 100.55 mg/kg) accordingly, and in remission period were 133.94 mg/kg (from 60.54 to 583.33 mg/kg) and 45.31 mg/kg (from 7.59 to 48.31 mg/kg, respectively). Both calprotectin and lactoferrin levels were significantly higher in active period than in remission period (χ2=10.63 and 8.18, while, P=0.005 and 0.017, respectively). Conclusions The level of fecal calprotectin and lactoferrin can reflect the pathological changes and severity of the intestinal mucosa.
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Objective To assess the predictive value of thiopurine methyltransferase genotyping and enzyme activity in relation to side effects in patients with inflammatory bowel disease (IBD) who were treated with azathioprine (AZA). Methods One hundred and eleven IBD patients (26 with ulcerative colitis and 86 with Cronh's disease) with indication of AZA administration between April 2004 and Dec. 2009 were enrolled. All patients received 2 mg/kg of AZA daily. Polymerase chain reaction and high performance liquid chromatography were used to genotype the TPMT * 2, * 3A, * 3B, * 3C and to detect TPMT activity, respectively. The association of TPMT genotype and activity with side effects was analyzed in patients treated with AZA for 24 weeks or more, or in those discontinued AZA because of adverse effects. Results Adverse effects were reported in 38(33. 9%) patients, the most frequent being myelosuppression (20. 5%). The frequency of TPMT * 3C heterozygous mutation was 0. 9% (1/112). The TPMT activity was (12. 9±4. 8) U/ml RBC with unimodal distribution. One patient with TPMT * 3C heterozygous mutation developed myelosuppression at the 4th week after AZA treatment. The TPMP genotype myelosuppression patients. Conclusions TPMT genotype mutation and low enzyme activity can be used to predict myelosuppression with high specifically and low sensitivity. In patients treated with AZA, co-administration of 5-ASA results in a high frequency of myelosuppression with no effect on TPMT activity.
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Objective To evaluate the prevalence of low bone mineral density in patients with inflammatory bowel disease(IBD) and to identify its risk factors. Methods A cross-sectional survey was carried out in IBD patients. Anthropemetric measures, biochemical markers of nutrition and bone mineral density measurement were completed for these patients as well as healthy control subjects. Results Seventy-seven Crohn's disease (CD) and 43 ulcerative colitis(UC) patients were enrolled, and 37 healthy volunteers were recruited as healthy controls(HC). The T value of CD patients, UC patients and HC was -1.72±1.20,-1.26±1.12 and-0.62±0.87 respectively and the T value of CD patients was significantly lower than that of HC (P=0.000). The prevelance of osteoporosis in CD, UC and HC was 23.3%, 14.0% and 0 respectively. The prevelance of osteoporosis in CD was higher than that in HC (P=0.003). Logistic regression analysis indicated that low BMI(BMI≤18.4 kg/m~2) was an independent risk factor for osteoporosis both in CD (OR=11.25,95% CI 3.198-39.580, P=0.000) and in UC (OR= 14. 50,95% CI 1.058-88.200, P=0.045) patients. Age, disease duration, clinical activity active index (CDAI), oral steroid therapy, immunosuppressant treatment and serum vitamin D concentration were not found to be correlated with osteoperosis in IBD patients. Conclusions Low bone mineral density is common in both CD and UC patients and low BMI is an independent risk factor for osteoporosis in IBD patients.
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Objective To compare the changes of serum C reactive protein (CRP) in different lesion site and activity so as to evaluate its worthy of an indicator of disease activity. Methods Forty-two patients with Crohn's disease (CD) were divided into small intestinal group and colonic group according to the involved lesions. Twenty-three cases of UC and 26 cases of inflammatory bowel disease (IBS)were served as controls. The serum level of hs-CRP was tested using latex-enhanced immunoturbidimetery. mg/L and (1.1±1.8)mg/L, respectively. Hs-CRP was elevated significantly in CD group compared to UC and IBS groups (P＜0.001). The ratio of patients whose hs-CRP exceeded 3 mg/L was 76.2%, 30.4% and 7.7% in CD, UC and IBS, respectively (P=0.000). The ratio was significantly higher in CD higher than that of small intestinal group [(11.9±7.6 )mg/L vs (6.8±7.2)rag/L, P =0.04]. The ratio of patients whose hs-CRP exceeded normal value was higher in colonic group than that in small CRP(≥10 rag/L). Among them, 4/17 were in remission, 3/11 in mild, 10/13 in moderate and 1/1 in severe according to the CDAI. The hs-CRP was correlated well with CDAI and ESR (r was 0.52 and 0.70 respectively, P＜0.001). Conclusions CRP can he used as a inflammatory marker for evaluating the disease activity of CD. The patients with small intestinal involvment may have lower CRP than those with colonic affection. The elevation of CRP was paralleled to the disease severity of CD.