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Active Crohn's Disease (active + crohn's_disease)
Selected AbstractsActive Crohn's disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal floraINFLAMMATORY BOWEL DISEASES, Issue 2 2008Alexander Swidsinski MD Abstract Background: The intestinal microflora is important in the pathogenesis of inflammatory bowel disease (IBD). The impact of its spatial organization on health and disease is unknown. Methods: We investigated sections of paraffin-embedded punched fecal cylinders. Fluctuations in spatial distribution of 11 bacterial groups were monitored in healthy subjects (n = 32), patients with IBD (n = 204), and other gastrointestinal diseases (n = 186) using fluorescence in situ hybridization (FISH). Results: The microbial structure differed in patients with Crohn's disease (CD), ulcerative colitis (UC), and healthy and disease controls. The profiles of CD and UC were distinctly opposite in 6 of 11 FISH probes used. Most prominent were a depletion of Faecalibacterium prausnitzii (Fprau<1 × 109/mL) with a normal leukocyte count in CD and a massive increase of leukocytes in the fecal-mucus transition zone (>30 leukocytes/104,m2) with high Fprau in patients with UC. These 2 features alone enabled the recognition of active CD (Crohn's Disease Activity Index [CDAI] >150) or UC (Clinical Activity Index [CAI] >3) with 79%/80% sensitivity and 98%/100% specificity. The mismatch in the sensitivity was mainly due to overlap between single IBD entities, and the specificity was exclusively due to the similarity of Crohn's and celiac disease. When inflammatory bowel disease (IBD) patients were pooled the sensitivity was 100% for severe disease, 84% for moderate activity, 72% for IBD with ,12 months remission, and 24% for IBD with >12 months remission. Conclusions: The fecal flora is highly structured and spatially organized. Diagnosing IBD and monitoring disease activity can be performed based on analysis of punched fecal cylinders independent from the patient's complaints. (Inflamm Bowel Dis 2007) [source] Anti tumour necrosis-, therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's diseaseIMMUNOLOGY, Issue 2 2008Ida Ricciardelli Summary Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T-cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases. Here we investigated whether Infliximab, a chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-, shown to be highly effective in the treatment of CD, has any effect on mucosal CD4+ CD25+ (FOXP3+) Tregs. Colonic mucosal biopsies from children with active Crohn's disease treated in vivo with Infliximab and controls were analysed to determine FOXP3 expression by immunofluorescence and reverse transcription,polymerase chain reaction. We observed that FOXP3+ T cells were significantly reduced in mucosa of CD patients with active disease compared with controls and restored to normal following Infliximab treatment. The frequency of FOXP3+ cells and mRNA expression was significantly increased in CD mucosa from patients treated in vivo with Infliximab compared with CD patients treated with conventional therapies. In conclusion, we show that Infliximab treatment does not solely neutralize soluble TNF-,, but also affects activation and possibly expansion of mucosal regulatory T cells. We suggest that anti TNF-, immunotherapy can also restore mucosal homeostasis in Crohn's disease. [source] Preliminary results obtained with cefoperazone plus corticosteroids in the treatment of active Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 8 2009Ezio Gaia MD No abstract is available for this article. [source] Low counts of Faecalibacterium prausnitzii in colitis microbiotaINFLAMMATORY BOWEL DISEASES, Issue 8 2009H. Sokol MD Abstract Background: The intestinal microbiota is suspected to play a role in colitis and particularly in inflammatory bowel disease (IBD) pathogenesis. The aim was to compare the fecal microbiota composition of patients with colitis to that of healthy subjects (HS). Methods: fecal samples from 22 active Crohn's disease (A-CD) patients, 10 CD patients in remission (R-CD), 13 active ulcerative colitis (A-UC) patients, 4 UC patients in remission (R-UC), 8 infectious colitis (IC) patients, and 27 HS were analyzed by quantitative real-time polymerase chain reaction (PCR) targeting the 16S rRNA gene. Bacterial counts were transformed to logarithms (Log10 CFU) for statistical analysis. Results: Bacteria of the phylum Firmicutes (Clostridium leptum and Clostridium coccoides groups) were less represented in A-IBD patients (9.7; P = 0.004) and IC (9.4; P = 0.02), compared to HS (10.8). Faecalibacterium prausnitzii species (a major representative of the C. leptum group) had lower counts in A-IBD and IC patients compared to HS (8.8 and 8.3 versus 10.4; P = 0.0004 and P = 0.003). The Firmicutes/Bacteroidetes ratio was lower in A-IBD (1.3; P = 0.0001) and IC patients (0.4; P = 0.002). Compared to HS, Bifidobacteria were less represented in A-IBD and IC (7.9 and 7.7 versus 9.2; P = 0.001 and P = 0.01). Conclusions: The fecal microbiota of patients with IBD differs from that of HS. The phylum Firmicutes and particularly the species F. prausnitzii, are underrepresented in A-IBD patients as well as in IC patients. These bacteria could be crucial to gut homeostasis since lower counts of F. prausnitzii are consistently associated with a reduced protection of the gut mucosa. (Inflamm Bowel Dis 2009) [source] Catheter-related septic thrombosis of superior vena cava and right heart in a patient with active Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 12 2008J.S. Souza MD No abstract is available for this article. [source] Functional gastrointestinal disorders and visceral hypersensitivity in children and adolescents suffering from Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 11 2008Christophe Faure MD Abstract Background: Symptoms of abdominal pain are reported by children with active Crohn's disease (CD). During remissions abdominal pain improves in most children but some of them continue to experience pain. We hypothesized that these patients may suffer from protracted abdominal pain related to functional gastrointestinal disorders (FGID) and visceral hypersensitivity. The objective was to characterize the symptoms and to measure the rectal sensory threshold for pain (RSTP) by barostat in CD children and adolescents suffering from abdominal pain despite remission. Methods: Eight patients (median age 14.5 years; range 9.8,17) with quiescent CD but suffering from chronic abdominal pain were studied by rectal barostat. At the same time they completed validated questionnaires to assess FGID, anxiety, and depression. They were compared to 10 control children and 8 children with FGID also investigated in our laboratory. Results: All patients fulfilled Rome II criteria for irritable bowel syndrome (n = 5), functional abdominal pain (n = 2), and functional dyspepsia (n = 1). RSTP was significantly lower in CD patients compared to the normal controls: median (range) 25 mmHg (15,29) versus 40 mmHg (30,48) (P < 0.01). RSTP was similar in patients and children with FGID. Rectal compliance was similar in patients, children with FGID, and controls. Seven of the 8 patients had scores indicating an anxiety problem. Conclusions: Protracted abdominal pain that affects children and adolescents with quiescent CD is related to FGID associated with visceral hypersensitivity and anxiety. The incidence of FGID in children suffering from CD requires further investigation. (Inflamm Bowel Dis 2008) [source] Is there a role for multidrug therapy in active Crohn's disease?INFLAMMATORY BOWEL DISEASES, Issue S2 2008Alastair Forbes BSc No abstract is available for this article. [source] Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): Upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p.His161Arg polymorphism in IBDINFLAMMATORY BOWEL DISEASES, Issue 4 2008Julia Seiderer MD Abstract Background: Interleukin (IL)-17F, produced in IL-23R-expressing Th17 cells, is a novel member of the IL-17 cytokine family. Given the association of IL23R with inflammatory bowel disease (IBD), we characterized the role of IL-17F in IBD including its intestinal gene expression and the effect of the IL17F p.His161Arg polymorphism on disease susceptibility and phenotype of Crohn's disease (CD) and ulcerative colitis (UC). In addition, we analyzed the IL17F p.His161Arg polymorphism for potential epistasis with IL23R and NOD2/CARD15 variants. Methods: Intestinal IL-17F mRNA expression was measured by quantitative polymerase chain reaction (PCR). Genomic DNA from 1682 individuals (CD: n = 499; UC: n = 216; controls: n = 967) was analyzed for the presence of the IL17F p.His161Arg polymorphism, the 3 NOD2 variants, p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008, and 10 CD-associated IL23R variants. Results: Intestinal IL-17F mRNA expression was 4.4-fold increased in inflamed colonic lesions compared to uninflamed biopsies in CD (P = 0.016) but not in UC. However, the mean intestinal IL-17F mRNA expression was higher in UC than in CD (P < 0.0001). The IL17F p.His161Arg substitution was observed with similar frequencies in IBD patients and controls and was not associated with a certain disease phenotype, but weakly associated with a low body mass index (BMI; P = 0.009) and an earlier age of disease onset (P = 0.039) in UC. There was no evidence for epistasis between the IL17F p.His161Arg polymorphism and IBD-associated single nucleotide polymorphisms within the IL23R gene. Conclusions: Intestinal IL17F gene expression is increased in active CD. The IL17F p.His161Arg polymorphism is not associated with IBD susceptibility and has no epistatic interaction with CD-associated IL23R variants. (Inclamm Bowel Dis 2007) [source] Carcinoid tumors are 15 times more common in patients with Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 9 2007N.E. West Abstract Background: The coexistence of intestinal neoplasms with Crohn's disease (CD) has been reported, but the evidence of an increased risk of carcinoid tumor with Crohn's disease has been mixed. We present 4 patients with CD with associated carcinoid tumor. Methods: The charts of 111 patients with CD who had undergone resection between June 2001 and March 2005 were reviewed. The number of incidental carcinoid tumors in patients who underwent an appendectomy was used as a control. Results: Four cases of carcinoid tumor discovered in patients at resection for CD were identified. None had metastatic disease or carcinoid syndrome. These included 1 cecal (1 mm), 2 appendiceal (3 and 7mm), and 1 transverse colon (7 mm) carcinoid tumors. None of the carcinoid tumors were identified in regions of active Crohn's disease. The incidence of carcinoid tumor in patients with Crohn's disease was 4 of 111 (3.6%). In comparison, 3 of 1199 patients (0.25%) who had appendectomies were identified as having appendiceal carcinoid tumor. Crohn's disease was associated with an increased incidence of carcinoid tumor; OR 14.9 (95% CI 2.5,102.5), P < 0.0001. Conclusions: There was a significantly increased incidence of carcinoid tumor in our Crohn's patients compared to the control patients. None of the carcinoid tumors developed in areas of Crohn's disease. This suggests that the development of carcinoid tumors may be secondary to distant proinflammatory mediators, rather than a local inflammatory effect from adjacent Crohn's disease. Patients with CD may be at increased risk of developing a carcinoid tumor. (Inflamm Bowel Dis 2007) [source] Infliximab and the risk of latent viruses reactivation in active Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 7 2007Alessandro Lavagna MD Abstract Background: Infliximab is used for refractory Crohn's disease but there are concerns regarding long-term safety. Recently, JC-polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short-term effect of infliximab on reactivation of several harmful latent viruses. Methods: Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein,Barr virus (EBV), human herpes virus-6, (HHV-6), -7, -8, and cytomegalovirus (CMV). Results: Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV-positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV-PCR tests were transiently positive (>40 copies/105 Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV-6, -7, and -8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV-PCR-positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. Conclusions: Our results support the safety of short-term infliximab treatment with respect to latent virus reactivation. The long-term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring. (Inflamm Bowel Dis 2007) [source] Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibodyINFLAMMATORY BOWEL DISEASES, Issue 1 2006Ivan J Fuss MD Abstract Background: Interleukin (IL)-12p70 and IL-23 are key T helper-1 (TH1) cytokines that drive the inflammation seen in numerous models of intestinal inflammation. These molecules contain an identical p40 chain that is bound to a p35 chain in IL-12 and a p19 chain in IL-23, making both potentially susceptible to modulation by an anti-IL-12p40 monoclonal antibody (mAb). Methods: In the present study, we sought to determine whether active inflammation in Crohn's disease (CD) is associated with the increased synthesis of both of these cytokines and whether patients treated with an anti-IL-12p40 mAb down-regulate IL-23 as well as IL-12p70 as previous reported. Results: To this end we initially determined that IL-12p70 secretion by control and CD antigen-presenting cells (macrophages) in lamina propria mononuclear populations is optimized by stimulation with CD40L and interferon-,. In subsequent studies using these stimulation conditions we found that patients with CD manifested both increased IL-12p70 and IL-23 secretion before anti-IL-12p40 mAb treatment and normal levels of secretion of these cytokines following cessation of treatment. Antigen-presenting cells in lamina propria mononuclear cells from ulcerative colitis patients, in contrast, produced only baseline levels of IL-23. Finally, we found that IL-23-induced T cell production of IL-17 and IL-6 are also greatly reduced after antibody treatment. The latter data are parallel to those from previous studies showing that anti-IL-12p40 down-regulates IFN-, and tumor necrosis factor-, secretion. Conclusions: We conclude that CD but not ulcerative colitis is associated with high levels of both IL-12p70 and IL-23 secretion as well as the secretion of downstream effector cytokines, and that this cytokine production is down-regulated following administration of IL-12p40 mAb. [source] Impact of elemental diet on mucosal inflammation in patients with active Crohn's disease: Cytokine production and endoscopic and histological findingsINFLAMMATORY BOWEL DISEASES, Issue 6 2005Takayuki Yamamoto MD Abstract Background: The aim of this study was to examine the impact of elemental diet on mucosal inflammation in Crohn's disease (CD), mainly by cytokine measurements. Methods: Twenty-eight consecutive patients with active CD were treated with an elemental diet (Elental) for 4 weeks. The mucosal biopsies were obtained from the terminal ileum and large bowel before and after treatment. As a control group, mucosal biopsies were obtained from 20 patients without inflammation. Mucosal cytokine concentrations were measured by enzyme-linked immunosorbent assay. Results: After treatment, clinical remission was achieved in 20 patients (71%). Endoscopic healing and improvement rates were 44% and 76% in the terminal ileum and 39% and 78% in the large bowel, respectively. Histologic healing and improvement rates were 19% and 54% in the terminal ileum and 20% and 55% in the large bowel, respectively. Before treatment, the mucosal concentrations of interleukin (IL)-1,, IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, and tumor necrosis factor-, in the ileum and large bowel were significantly higher than in controls. These cytokine concentrations decreased to the levels of control after treatment. IL-1ra/IL-1, ratio in the ileum and large bowel was significantly lower than in controls before treatment. The ratio increased to the level of controls after treatment. The endoscopic and histologic healing of the mucosal inflammation was associated with a decline of the mucosal cytokines and an increase of the IL-1ra/IL-1, ratio. Conclusions: The elemental diet (Elental) reduced mucosal cytokine production and corrected an imbalance between proinflammatory and anti-inflammatory cytokines in CD. [source] Anti-inflammatory role of interleukin-15 in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2005Manuel A Silva MD Abstract Background: Interleukin (IL)-15 is overexpressed in intestinal tissue with active Crohn's disease (CD). However, its role in the pathogenesis of the disease remains uncertain. We studied the effects of IL-15 on colonic mucosal proinflammatory cytokine response in vitro using organ culture of human colonic explants. Methods: Colonic tissue was obtained from (1) resections in pediatric CD patients (inflamed and noninflamed) and (2) rectal biopsies in patients with CD undergoing colonoscopy (n = 31) and controls (n = 9). In preliminary experiments, explants from the resections were cultured in the presence or absence of a simulated TH1 stimulation using ionomycin (Io) and phorbol-myristate-acetate (PMA), with or without IL-15, or in medium alone. Rectal biopsies were cultured in the same conditions as above, with or without adding a monoclonal anti-IL-15 neutralizing antibody (mAb). Levels of interferon (IFN)-,, tumor necrosis factor (TNF)-,, and IL-2R, were measured by enzyme-linked immunosorbent assay. Results: IL-15, in the absence of Io + PMA, did not induce the expression of IFN-,, TNF-,, or IL-2R,. Only inflamed explants from resections stimulated with Io + PMA expressed IFN-,, TNF-,, and IL-2R,. This TH1 stimulatory effect was inhibited by IL-15 in a dose-dependent fashion. In rectal biopsy explants, inflamed, noninflamed CD, and control tissue responded to stimulation with Io + PMA (P < 0.05) with increased IFN-, and TNF-, (P < 0.05). This response was again inhibited by IL-15. The inhibitory effect of IL-15 was specifically reversed by anti-IL-15 mAb (P < 0.05). The data for the CD group were also analyzed according to the severity of colonic inflammation and medication use. Conclusions: Our results suggest a possible anti-inflammatory role for IL-15 in CD. We postulate that its overexpression in CD potentially represents a protective mechanism against the exaggerated TH1 immune response. [source] Use of 6-mercaptopurine/azathioprine as the immunomodulator of choice for moderately active Crohn's disease.INFLAMMATORY BOWEL DISEASES, Issue 2 2005Balance No abstract is available for this article. [source] Looking in the rear view mirror at pentasa in active Crohn's disease: Results may be smaller than they first appearINFLAMMATORY BOWEL DISEASES, Issue 1 2005David A. Schwartz MD No abstract is available for this article. [source] Serum bFGF and VEGF correlate respectively with bowel wall thickness and intramural blood flow in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 5 2004Dr. Antonio Di Sabatino MD Abstract Serum levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF),two factors known to promote tissue repair, fibroblast proliferation, and angiogenesis,were measured in Crohn's disease patients and correlated with bowel wall thickness (BWT), measured by conventional grey scale ultrasonography, and with the ileal intramural vessel flow, measured by contrast-enhanced color Doppler imaging. Serum samples were obtained from 25 patients with active Crohn's disease and 22 healthy volunteers, all sex- and age-matched. Serum bFGF and VEGF levels were measured by ELISA assay. All the patients were examined with conventional transabdominal bowel sonography. Color Doppler of the intramural enteric vessels was then performed after the intravenous injection of Levovist, a galactose-based sonographic contrast agent. In Crohn's disease patients, serum bFGF and VEGF were significantly higher compared with healthy volunteers. A positive correlation between serum bFGF and BWT and between serum VEGF and color Doppler signal intensity was found. The raised serum bFGF levels in Crohn's disease patients with intestinal strictures compared with patients with other phenotypes (fistulizing, inflammatory), together with the correlation observed between serum bFGF and BWT, suggests a possible involvement of bFGF in the process of transmural fibrogenesis in Crohn's disease. The higher levels of VEGF in those patients with increased intramural blood flow suggests that VEGF may be considered a marker of angiogenesis in this condition. [source] Infliximab improves quality of life in patients with Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2002Dr. Gary R. Lichtenstein Abstract Objective The aim of this study was to assess the effect of infliximab on quality of life in patients with active Crohn's disease (CD) inadequately responsive to concomitant therapies. Methods We examined responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) from patients enrolled in a previously reported, randomized, placebo-controlled study. Patients with active CD received a single intravenous infusion of either placebo or infliximab 5, 10, or 20 mg/kg. Most patients received stable doses of mesalamine, corticosteroids, azathioprine, or 6-mercaptopurine throughout the study. Changes from baseline in overall IBDQ score and individual dimensions at 4 weeks postinfusion were compared. Results Patients treated with infliximab had a significantly larger improvement in overall IBDQ score than those treated with placebo at 4 weeks (p < 0.001). Infliximab-treated patients also had larger improvements in all IBDQ dimensions: bowel (p = 0.007), social (p = 0.002), emotional (p < 0.001), and systemic (p < 0.001). A significantly larger proportion of infliximab-treated patients reported having normal or near-normal frequency of bowel movements in the past week (p < 0.001), full or a lot of energy (p = 0.019), and no or hardly any difficulty doing leisure or sports activities (p = 0.011), and being extremely or very satisfied with their personal life (p = 0.046). They also significantly differed in responses regarding fatigue, frustration, ability to work, general well-being, depression, anxiety, and anger resulting from bowel problems. Conclusions These results indicate that infliximab significantly improved quality of life in patients with active CD, increasing their ability to work and participate in leisure activities, and decreasing feelings of fatigue, depression, and anger. [source] Preliminary study of ciprofloxacin in active Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 1 2002Dr. George L. Arnold Abstract Based on limited reports of the successful use of antibiotics in the treatment of Crohn's disease (CD) and on the possibility that intestinal bacteria may be one of the etiologic factors playing a role in the pathogenesis of this condition, we undertook a study to evaluate the use of a broad-spectrum antibiotic in CD. Our team studied the efficacy of adding the antibiotic ciprofloxacin to the treatment of moderately active, but resistant cases of CD. Forty-seven adults with moderately active CD were randomly assigned treatment with ciprofloxacin 500 mg twice daily versus placebo twice daily for 6 months. The primary endpoint was the change in scores on the Crohn's Disease Activity Index (CDAI) from baseline to month 6. Although 47 patients were randomized, at 1 month of follow-up 28 patients received ciprofloxacin and 19 received placebo. The mean entry CDAI scores were not significantly different: 187 for the ciprofloxacin group versus 230 for the placebo group (p = 0.638). Mean CDAI scores at the completion of study were 112 for the ciprofloxacin group (n = 25) and 205 for the placebo group (n = 12), (p < 0.001). Disease remission is defined as a decrease in the CDAI score to less than 150 points. Our preliminary study suggests that ciprofloxacin may be an effective agent when added to the treatment of moderately active, resistant CD. [source] Adsorptive monocyte-granulocytapheresis (M-GCAP) for refractory Crohn's disease,JOURNAL OF CLINICAL APHERESIS, Issue 4 2004Takeshi Kusaka Abstract Six patients with active Crohn's disease (CD) unresponsive to conventional medications (CM) were treated with Monocyte-granulocytapheresis (M-GCAP). CD patients who scored 200,400 points in Crohn's disease activity index (CDAI) in spite of receiving CM, including enteral nutrition, for at least 2 weeks were enrolled in our double series trial. Each series had 5 weekly M-GCAP and 2 follow-up weeks, and each M-GCAP treated 1,800 ml of patient's peripheral blood. After the 1st series, patients who decreased more than 50 points on the CDAI were deemed responders and enrolled in the second series. Patients with a CDAI score less than 150 points were considered in remission. The patients' quality of life was evaluated using an index (IBDQ) before and after the 1st series. The CDAI was significantly decreased comparing before and after the 1st series (258.2 ± 36.2 vs. 166.5 ± 16.6; P < 0.02). 50% of patients (3/6) responded to the therapy, and one case (16.7%) could be induced to remission. Significant removal was revealed only for white blood cells (25.6 ± 16.9%; P < 0.05), especially granulocytes (29.5 ± 22.5%; P < 0.05). A statistically significant improvement of IBDQ was revealed in the responders' group (162.3 ± 17.2 vs. 189.3 ± 11.5; P < 0.03). M-GCAP could be an effective adjunctive therapy for active CD patients unresponsive to CM allowing them to maintain a high QOL. However, it might be difficult to improve patients who could not be induced to remission after the 1st series by applying another series. J. Clin. Apheresis 19:168,173, 2004. © 2004 Wiley-Liss, Inc. [source] Interleukin-27 polymorphisms are associated with inflammatory bowel diseases in a Korean populationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2009Chun-Shi Li Abstract Background and Aims:, The cytokine interleukin (IL)-27 is composed of two subunits, Epstein,Barr virus-induced gene 3 (EBI3) and p28, and IL-27 is a novel IL-12 family member that mediates between the innate and adaptive immune systems. We previously identified four polymorphisms in the human IL-27 gene and we suggested that the polymorphism of IL-27 is associated with the susceptibility to asthma. IL-27 transcripts are significantly elevated in active Crohn's disease (CD) but not in ulcerative colitis (UC). To determine whether these IL-27 single nucleotide polymorphisms are associated with the susceptibility to inflammatory bowel disease (IBD), the genotype and allelic frequencies of the IL-27 polymorphisms were analyzed between the IBD patients and the healthy controls. Methods:, Genotype analysis of the IL-27 gene was performed by the single-base extension (SBE) method. The haplotype frequencies of IL-27 for multiple loci were estimated using the expectation maximization (EM) algorithm. Results:, The genotype frequencies of the g.-964A > G polymorphism in the IBD patients were significantly different from those of the healthy control group (P = 0.001). In both the UC and CD patients, the genotype frequencies of the g.-964A > G polymorphism were also significantly different from the frequencies of the healthy control group (P = 0.009). The frequencies of the AGT and GGT haplotypes were significantly different between the healthy control group and the IBD patient group (P = 0.00004 and 0.021, respectively). Conclusion:, Our results suggest that the g.-964A > G polymorphism of the IL-27 gene located on the IBD1 locus might be associated with the susceptibility to IBD. [source] Clinical trial: the microbiological and immunological effects of synbiotic consumption , a randomized double-blind placebo-controlled study in active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010H. Steed Aliment Pharmacol Ther 2010; 32: 872,883 Summary Background, Crohn's disease is an inflammatory illness in which the immune response against gut microorganisms is believed to drive an abnormal immune response. Consequently, modification of mucosal bacterial communities, and the immune effects they elicit, might be used to modify the disease state. Aim, To investigate the effects of synbiotic consumption on disease processes in patients with Crohn's disease. Methods, A randomized, double-blind placebo-controlled trial was conducted involving 35 patients with active Crohn's disease, using a synbiotic comprising Bifidobacterium longum and Synergy 1. Clinical status was scored and rectal biopsies were collected at the start, and at 3- and 6-month intervals. Transcription levels of immune markers and mucosal bacterial 16S rRNA gene copy numbers were quantified using real-time PCR. Results, Significant improvements in clinical outcomes occurred with synbiotic consumption, with reductions in both Crohn's disease activity indices (P = 0.020) and histological scores (P = 0.018). The synbiotic had little effect on mucosal IL-18, INF-, and IL-1,; however, significant reductions occurred in TNF-, expression in synbiotic patients at 3 months (P = 0.041), although not at 6 months. Mucosal bifidobacteria proliferated in synbiotic patients. Conclusion, Synbiotic consumption was effective in improving clinical symptoms in patients with active Crohn's disease. [source] Clinical trial: the effects of certolizumab pegol therapy on work productivity in patients with moderate-to-severe Crohn's disease in the PRECiSE 2 studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2010B. G. FEAGAN Aliment Pharmacol Ther,31, 1276,1285 Summary Background, The effect of certolizumab pegol on employment status and work productivity has not been previously assessed. Aim, To assess the impact of treatment with certolizumab pegol, the only PEGylated, Fab, TNF antagonist, on work productivity in patients with active Crohn's disease (CD) from the PRECiSE 2 study. Methods, Patients (n = 668) with active disease [CD activity index (CDAI) score of 220,450] were treated with open-label subcutaneous certolizumab pegol 400 mg (week 0, 2, 4). Responders (n = 425) (,100-point decrease in CDAI from baseline) were randomized to receive certolizumab pegol 400 mg or placebo every 4 weeks until week 24, with final evaluation at week 26. Patients completed the Work Productivity and Activity Impairment for CD questionnaire (WPAI:CD) and the Inflammatory Bowel Disease Questionnaire (IBDQ) at weeks 0, 6, 16 and 26 and at the withdrawal visit. Results, Work productivity improved following induction with certolizumab pegol. Between week 6 and 26, certolizumab pegol-treated patients experienced significant improvement in work productivity compared with placebo recipients (11% and 10% overall improvement in work and activity impairment, respectively). During the maintenance phase, impairments in productivity and activities due to CD were significantly less in the certolizumab pegol group than in the placebo group. Conclusion, Induction and maintenance therapy with certolizumab pegol significantly improved the work productivity of patients with active CD compared with those in the placebo group. [source] Clinical trial: the safety and short-term efficacy of recombinant cholera toxin B subunit in the treatment of active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010P. STÅL Aliment Pharmacol Ther,31, 387,395 Summary Background, The cholera toxin B subunit ameliorates experimentally induced colitis in mice. In humans, cholera toxin B subunit has never been tested in the treatment of Crohn's disease (CD). Aim, To evaluate the safety and efficacy of treatment with recombinant cholera toxin B subunit of patients with CD. Methods, An open-label, multicentre, nonrandomized trial including 15 patients with mild/moderate CD. Patients received an oral solution of 5 mg recombinant cholera toxin B subunit three times weekly for 2 weeks. Reduction in CD Activity Index (CDAI) with >100 between baseline and days 15, 29, 42 and 70 defined clinical response. Patients with CDAI score ,150 were defined as being in remission. Results, A significant decrease in CDAI score was observed. Response rates were 40% in the full analysis set and 42% in the per protocol analysis. Two patients receiving adjuvant treatment after day 29 were excluded, after which 40% were in remission at 4 weeks and 30% at 8 weeks post-treatment. Mild side effects (arthralgia, headache and pruritus) were seen in 33% of patients. Conclusions, Treatment with recombinant cholera toxin B subunit was safe. Approximately 40% of patients with active CD responded to treatment. Randomized studies are needed to establish the clinical efficacy of recombinant cholera toxin B subunit. [source] An analysis of the placebo effect in Crohn's disease over timeALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010W. C. GALLAHAN Summary Background, Randomized, placebo controlled trials are used to assess the efficacy of therapies for Crohn's disease. The placebo response and remission rates vary among studies. Aim, To analyse how the placebo response and remission rates in Crohn's trials have changed over time in the era of parenteral biologic therapies. Methods, A search for randomized, placebo-controlled trials of parenteral biologic therapies for active Crohn's disease was conducted using online databases. The placebo response and remission rates and study week of evaluation were recorded for each trial. The placebo response and remission rates were analysed as functions of publication date and study week of evaluation. Results, The odds of a placebo-induced remission and response significantly increased as the week of evaluation increased. The placebo remission rate increased significantly with year of publication. Adjusted for week of evaluation, this increase in placebo remission rate over time was no longer significant. The increase in the placebo response over this time period was not statistically significant. Conclusion, The observed increase in placebo remission rates over time in trials of parenteral biologic therapies in Crohn's disease is explained by longer times to the primary endpoint in more recent trials. [source] Influence of standard treatment on ileal and colonic antimicrobial defensin expression in active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009I. KÜBLER Summary Background, Crohn's Disease (CD), a chronic intestinal inflammation, is currently treated primarily by therapeutics which are directed against inflammatory responses. Recent findings though suggest a central role of the innate immune barrier in the pathophysiology. Important factors providing this barrier are antimicrobial peptides like the ,- and ,-defensins. Little is known about in vivo effects of common drugs on their expression. Aim, To analyse the influence of corticosteroids, azathioprine and aminosalicylate treatment on ileal and colonic antimicrobial peptides in active CD and also assess the role of inflammation. Methods, We measured the expression of antimicrobial peptides and pro-inflammatory cytokines in 75 patients with active CD. Results, Ileal and colonic ,- and ,-defensins as well as LL37 remained unaffected by corticosteroids, azathioprine or aminosalicylate treatment. Additionally, we did not observe a negative coherency between Paneth cell ,-defensins and any measured cytokines. HBD2 and LL37 unlike HBD1 levels were linked to inflammatory cytokines and increased in highly inflamed samples. Conclusions, Current oral drug treatment seems to have no major effect on the expression of antimicrobial peptides. In contrast to HBD2 and LL37, ileal levels of HD5 and HD6 and colonic HBD1 level are independent of current inflammation. Innovative drugs should aim to strengthen protective innate immunity. [source] Evaluation of the meaningfulness of health-related quality of life improvements as assessed by the SF-36 and the EQ-5D VAS in patients with active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009G. COTEUR Summary Background, Crohn's disease (CD) is a chronic inflammatory illness characterized by episodic abdominal pain, diarrhoea, fever, bleeding and obstruction. While the Crohn's Disease Activity Index (CDAI) remains the most commonly accepted measure for assessing the disease status in clinical trials, patient-reported outcome (PRO) instruments are being utilized more frequently to provide information about health-related quality of life (HRQOL). To facilitate interpretation of results, it is common to identify a meaningful unit of PRO score change, such as a minimal clinically important difference (MCID). Aim, To define and apply MCID estimates for the SF-36 and EuroQol-5D visual analogue scale (EQ-5D VAS) for use in CD treatment evaluation. Methods, Data from two phase III randomized controlled trials of certolizumab pegol were utilized. MCID estimates were computed from one trial using anchor-based and distribution-based methods. These estimates were applied to data from the other trial. Results, SF-36 PCS and MCS MCID estimates ranged from 1.6 to 7.0 and 2.3 to 8.7 respectively, depending on approach. EQ-5D VAS MCID estimates ranged from 4.2 to 14.8. Conclusions, For the first time, the MCID values provided interpretation guidelines for PRO results in CD. This research demonstrates that patients treated with certolizumab pegol benefit from meaningful and sustained HRQOL improvements. [source] Clinical trial: randomized study of clarithromycin versus placebo in active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2008K. LEIPER Summary Background, Crohn's disease is characterized by defective innate immune responses to intestinal bacteria. Clarithromycin is a broad-spectrum antibiotic that has good penetration into macrophages. Aim, To assess the efficacy of clarithromycin in active Crohn's disease. Methods, Patients with Crohn's disease activity index > 200 and serum C-reactive protein , 10 mg/L were randomized to receive clarithromycin 1 g o.d. or placebo for 3 months. Patients taking more than 10 mg/day prednisolone or 3 mg/day budesonide were excluded. Primary outcome was remission (CDAI , 150) or response (fall in CDAI , 70 from pre-treatment level) at 3 months. Results, The trial was stopped after 41 patients had been recruited because of poor overall efficacy. There was no difference in combined remission or response rates at 3 months between clarithromycin: 26% (five of 19) and placebo: 27% (six of 22) (P = 1.00). The mean (s.d.) fall in Crohn's disease activity index was 35 (80) clarithromycin and ,2 (114) placebo (P = 0.24). However, post hoc analysis showed a significant difference in response/remission determined by Crohn's disease activity index after 1 month: 53% (10 of 19) clarithromycin vs. 14% (three of 22) placebo (P = 0.01). Conclusion, Clarithromycin 1 g for 3 months is ineffective in active Crohn's disease but possible benefit was observed at 1 month, suggesting that an initial effect may be attenuated by subsequent bacterial resistance. [source] Review article: appropriate use of corticosteroids in Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2007P. M. IRVING Summary Background, Corticosteroids are a well-established treatment for active Crohn's disease and have been widely used for decades. It has become apparent, however, that a proportion of patients either fails to respond to corticosteroids or is unable to withdraw from them without relapsing. Furthermore, their use is associated with a range of side effects, such that long-term treatment carries unacceptable risk. Aim, To review the evidence regarding the appropriate use of corticosteroids in Crohn's disease, along with their side effects, safety and alternatives. Methods, To collect relevant articles, a PubMed search was performed from 1966 to November 2006 using the terms ,steroid', ,corticosteroid', ,glucocorticoid', ,prednisolone', ,prednisone', ,methylprednislone', ,hydrocortisone', ,dexamethasone' and ,budesonide' in combination with ,Crohn(s) disease'. Relevant articles were reviewed, as were their reference lists to identify further articles. Results, When used correctly, corticosteroids are a highly effective, well tolerated, cheap and generally safe treatment for active Crohn' disease. Nevertheless, approximately 50% of recipients will either fail to respond (steroid-resistant) or will be steroid dependent at 1 year. Newer alternatives to corticosteroids are not, however, without risk themselves and, moreover, are not necessarily available universally. Conclusions, Steroids are used widely to treat Crohn's disease, a situation that is unlikely to change in the near future. Accordingly, efforts should be made to ensure that they are used correctly and that their side effects are minimized. Reference is made to recently published guidelines and a simplified ,users guide' is presented. [source] Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acidsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2005A. A. NIELSEN Summary Background :,Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract. Polyunsaturated omega-3 fatty acids given orally may reduce the secretion of proinflammatory cytokines and hereby downregulate the inflammatory process. Aim :,To assess the effects of enteral fatty acids, in the form of Impact Powder (Novartis, Switzerland), as adjuvant therapy to corticosteroid treatment on the proinflammatory and anti-inflammatory cytokine profiles in patients with active Crohn's disease. Methods :,The proinflammatory and anti-inflammatory cytokines were measured in plasma from 31 patients with active Crohn's disease. Patients were randomized for oral intake of omega-3 fatty acid (3-Impact Powder) or omega-6 fatty acids (6-Impact Powder). Clinical and biochemical markers of inflammation were studied at baseline and after 5 and 9 weeks. Results :,Within the 3-Impact Powder group, no significant changes in concentrations of interleukin-6, interferon- ,, monocyte chemoattractant protein-1, interleukin-2, interleukin-5 and interleukin-10, whereas a significant differences in concentration of interleukin-1, and interleukin-4 were observed during therapy. Within the 6-Impact Powder group a significant changes in concentrations of interleukin-1,, interleukin-6, interferon- ,, monocyte chemoattractant protein-1, interleukin-2, interleukin-4, interleukin-5 and interleukin-10 were observed. Conclusions :,The 3-Impact Powder showed immunomodulatory properties and might inhibit an increase of proinflammatory cytokines in contrast to the 6-Impact Powder. [source] An open-labelled study of granulocyte colony-stimulating factor in the treatment of active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2005J. R. Korzenik Summary Background :,Immunodeficiency syndromes associated with a Crohn's-like illness suggest innate immune defects may lead to Crohn's disease. Anecdotal cases using haemopoietic colony-stimulating factors report improvement in intestinal disease associated with these syndromes. Aim :,To test the safety and efficacy of recombinant human granulocyte colony-stimulating factor in active Crohn's disease. Methods :,In an open-labelled 12-week trial, patients with a Crohn's Disease Activity Index between 220 and 450 were treated with recombinant human granulocyte colony-stimulating factor (filgrastim, Neupogen). Concomitant immunosuppressants were prohibited except prednisone ,20 mg/day. Patient's received recombinant human granulocyte colony-stimulating factor 300 mcg daily subcutaneously adjusted to achieve an absolute neutrophil count between 25 and 35 × 109/L. Results :,Twenty patients were enrolled with a mean initial Crohn's Disease Activity Index of 307 (range: 234,428). Fifteen patients (75%) completed 8 weeks; 13 patients (65%) completed 12 weeks with the mean Crohn's Disease Activity Index for patients continuing through those times of 196 (range: 36,343) and 162 (range: 20,308), respectively. At week 12, 11 patients (55%) demonstrated a decrease of at least 70 points; five (25%) achieved a sustained remission. The mean decrease was statistically significant at each assessment time-point. Three of four patients with fistulae had a positive response. Adverse effects included bone pain, mostly mild resolving with continued treatment. One patient was hospitalized with a viral-like syndrome but it is uncertain if this was treatment related. Conclusion :,Recombinant human granulocyte colony-stimulating factor is safe and potentially effective therapy for active Crohn's disease. [source] | ||||||||||||||||||||||