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Clinical Remission (clinical + remission)
Selected AbstractsMedium-term results of oral tacrolimus treatment in refractory inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 2 2007Siew C. Ng MRCP Abstract Background: This study aimed to evaluate the efficacy of oral tacrolimus in patients with inflammatory bowel disease (IBD) refractory to conventional therapy, including azathioprine, 6-mercaptopurine, and infliximab. Methods: Retrospective review of all patients with IBD treated with oral tacrolimus was undertaken. Tacrolimus was administered at an initial dose of 0.05 mg/kg twice daily, aiming for serum trough levels of 5,10 ng/mL. We evaluated clinical response, a retrospective estimated Crohn's disease activity index (CDAI) for Crohn's disease (CD), modified Truelove-Witts index for ulcerative colitis (UC), and modified pouch disease activity index (mPDAI) for pouchitis. Patients had been monitored clinically for benefit and side effects and by whole blood tacrolimus level approximately every 4 weeks for the duration of treatment. Clinical remission was defined as an estimated CDAI <150 (CD), an inactive disease score on the Truelove-Witts index (UC), and mPDAI <5 (pouchitis). Results: Twelve patients with CD, six with UC, and one with pouchitis, all resistant to previous therapies, were treated for a median of 5 months. After 4 weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a clinical response. There was a median reduction of the estimated CDAI of 108 points (range 35,203; P = 0.002) and stool frequency of three per day at week 4. Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the end of follow-up. Side effects included temporary elevated creatinine (n = 1), tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four patients discontinued treatment due to side effects. Conclusion: Oral tacrolimus is well tolerated and effective in patients with refractory IBD in the short- to medium-term. Further controlled, long-term evaluation is warranted. (Inflamm Bowel Dis 2007) [source] Oral mesalamine and clinical remission are associated with a decrease in the extent of long-standing ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 7 2006Michael F. Picco MD Abstract Objective: To compare colonoscopy alone with surveillance biopsy for the determination of anatomic extent in long-standing ulcerative colitis (UC). To assess the influences of mesalamine use and clinical disease activity on the change of histologic extent with time. Materials and Methods: Disease extent (proctosigmoiditis, left-sided colitis, or pancolitis) measured by colonoscopy and surveillance biopsy was compared among 212 consecutive patients with long-standing UC. Among the 102 patients who had 2 consecutive colonoscopies with surveillance biopsies, the following influences on change in histologic extent were determined: disease activity, mesalamine use, age at disease onset, folic acid, corticosteroid and azathioprine/6-mercaptopurine use, and time between colonoscopies. Results: Agreement between gross and microscopic findings was poor (, = 0.39). Colonoscopy underestimated and overestimated extent in 25.9% and 8.5%, respectively. Microscopic distribution between consecutive colonoscopies remained the same in 60.8%. Where distribution changed, an increase was twice as common as a decrease in extent. There was no difference in age at onset, time between colonoscopies, or disease duration among those with an increase, decrease, or no change in extent. Clinical remission and oral mesalamine were independently associated with 10.7 and 5.8 times the odds of a decrease in disease extent, respectively. Folic acid, topical mesalamine, corticosteroids, and immunomodulators did not influence change in extent. Conclusions: UC extent is best determined by surveillance biopsy. Among patients with long-standing UC, histologic extent fluctuates with time. Disease remission and oral mesalamine were independently associated with decreases in disease extent. [source] Clinical trial: five or ten cycles of granulocyte,monocyte apheresis show equivalent efficacy and safety in ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2010A. U. DIGNASS Aliment Pharmacol Ther,31, 1286,1295 Summary Background, Ulcerative colitis is characterized by leucocyte infiltration into the colonic mucosa. Granulocyte,monocyte apheresis depletes these cells. Aim, To assess the non-inferiority of 5,10 apheresis treatments in patients with steroid-dependent or steroid-refractory ulcerative colitis. Methods, A total of 196 adults with moderate,severe ulcerative colitis were randomized 1:1 to 5 (n = 96) or 10 (n = 90) open label apheresis treatments. The primary endpoint was non-inferiority of clinical activity index score after 12 weeks. Results, The intent-to-treat population comprised 82 and 80 patients for the 5- and 10-treatment groups, respectively. The difference between the two groups in mean clinical activity index was 0.24 with an upper 95% confidence interval of 1.17, which was below a predefined non-inferiority threshold of 1.33. Clinical activity index score improved from baseline in both groups (from 8.7 to 5.6 with 5 treatments, and from 8.8 to 5.4 with 10), with no significant difference between the groups (P = 0.200). Outcomes for the 5- and 10-treatment groups were similar , Clinical remission: 44% and 40%, respectively (P = 0.636); clinical response: 56% and 59%, respectively (P = 0.753). The treatment was well tolerated in both groups. Conclusions, This prospective study comparing apheresis regimens in ulcerative colitis demonstrates that 5 treatments were not inferior to 10 treatments in steroid-refractory or -dependent ulcerative colitis. [source] Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010A. ANSARI Aliment Pharmacol Ther,31, 640,647 Summary Background, The thiopurine drugs, azathioprine and mercaptopurine (MP), are established treatments for IBD. However, therapeutic failure caused by adverse drug reactions occurs frequently. Aim, To study combination of allopurinol with reduced-dose thiopurine in an attempt to avoid adverse drug reactions in the treatment of IBD. Methods, Patients with drug reactions to full-dose thiopurines were recruited for combination therapy in two IBD centres in this retrospective study. Dosing was guided by measuring thiopurine methyltransferase (for UK patients) or thioguanine nucleotides and methyl-6MP (Australian patients). Response was monitored by clinical activity indices. Results, Of 41 patients, 25 had non-hepatic and 16 had hepatitic reactions. Clinical remission was achieved in 32 patients (78%) with a median follow-up of 41 weeks (range 0.5,400). Patients who did not respond to combination therapy tended to fail early with the same adverse reaction. The relative risk of having an adverse reaction with methyl-6MP in the top interquartile range was 2.7 (1.3,28) times that with methyl-6MP in the lower three quartiles (95% confidence interval). Conclusion, The combined experience from our centres is the largest reported experience of this combination therapy strategy in IBD, and the first to provide evidence for benefit in thiopurine and allopurinol co-therapy to avoid non-hepatitic adverse drug reactions. [source] Oral, colonic-release low-molecular-weight heparin: an initial open study of Parnaparin-MMX for the treatment of mild-to-moderate left-sided ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008L. PASTORELLI Summary Background, Efficacy of heparin and low-molecular-weight heparins (LMWHs) in inflammatory bowel disease (IBD) treatment has been suggested. The multimatrix oral formulation MMX releases active drugs in the colon, avoiding systemic absorption. Parnaparin sodium is the LMWH chosen to be carried in the MMX formulation. Aim, To assess the safety of three different oral dosages (70, 140 and 210 mg once daily) of Parnaparin-MMX (CB-01-05) in left-sided ulcerative colitis (UC). Methods, Left-sided UC patients, with a mild-to-moderate relapse were enrolled. All patients received Parnaparin-MMX for 8 weeks. Clinical Activity Index (CAI), Disease Activity Index (DAI), Endoscopic Activity Index and IBD-QoL were assessed throughout the study. A strict clinical and laboratory follow-up, including assessment of anti-factor Xa activity, was performed. Clinical remission was defined as CAI <4. Results, Ten UC patients were enrolled. One patient retired for clinical deterioration. No relevant side effects, including either interference with haemostasis parameters or increased bleeding, were observed. At the end of the treatment, seven patients (70%) were in clinical remission, only one achieving endoscopic healing. Mean final CAI, DAI and IBD-QoL scores were significantly improved from baseline. Conclusions, Parnaparin-MMX appears to be a safe treatment option in mild-to-moderate UC. Controlled studies are warranted. [source] Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus,ARTHRITIS & RHEUMATISM, Issue 8 2010Lingyun Sun Objective Umbilical cord (UC),derived mesenchymal stem cells (MSCs) have shown marked therapeutic effects in a number of diseases in animal studies, based on their potential for self-renewal and differentiation. No data are available on the effectiveness of UC MSC transplantation (MSCT) in human autoimmune disease. This study was undertaken to assess the efficacy and safety of allogeneic UC MSCT in patients with severe and treatment-refractory systemic lupus erythematosus (SLE). Methods We conducted a single-arm trial that involved 16 SLE patients whose disease was refractory to standard treatment or who had life-threatening visceral involvement. All of the patients gave consent and underwent UC MSCT. Clinical changes were evaluated before and after transplantation using the SLE Disease Activity Index (SLEDAI), measurement of serum antinuclear antibody (ANA), anti,double-stranded DNA (anti-dsDNA) antibody, serum complement C3 and C4, and albumin levels, and assessment of and renal function. Evaluation of potential mechanisms of MSCT effects focused on the percentage of peripheral blood Treg cells and serum levels of cytokines. Results From April 2007 to July 2009, a total of 16 patients with active SLE were enrolled and underwent UC MSCT. The median followup time after MSCT was 8.25 months (range 3,28 months). Significant improvements in the SLEDAI score, levels of serum ANA, anti-dsDNA antibody, serum albumin, and complement C3, and renal function were observed. Clinical remission was accompanied by an increase in peripheral Treg cells and a re-established balance between Th1- and Th2-related cytokines. Significant reduction in disease activity was achieved in all patients, and there has been no recurrence to date and no treatment-related deaths. Conclusion Our findings indicate that UC MSCT results in amelioration of disease activity, serologic changes, and stabilization of proinflammatory cytokines. These data provide a foundation for conducting a randomized controlled trial of this new therapy for severe and treatment-refractory SLE. [source] Clinical remission of idiopathic hypereosinophilic syndrome in a RottweilerAUSTRALIAN VETERINARY JOURNAL, Issue 8 2009FE James Idiopathic hypereosinophilic syndrome (HES) is a rare syndrome for which Rottweilers appear to over-represent the canine cases. A 6-month-old female entire Rottweiler presented with seizures following a traumatic incident. The dog was identified as having a marked, sustained eosinophilia and investigations did not identify an underlying cause. Concurrently, the dog had chronic eosinophilic hepatitis with impaired liver function and mesenteric eosinophilic lymphadenitis. The dog went on to have spontaneous resolution of HES and normal liver function was subsequently documented. To date, the dog is still alive, more than 4 years after initial presentation. The diagnosis of idiopathic HES in Rottweilers may not carry a poor prognosis and the condition may spontaneously resolve, even in cases with documented organ damage. [source] Successful management of histiocytic ulcerative colitis with enrofloxacin in two Boxer dogsAUSTRALIAN VETERINARY JOURNAL, Issue 1-2 2004DR DAVIES Two Boxer dogs with histologically confirmed histiocytic ulcera-tive colitis were treated with enrofloxacin, one as sole therapy and one in conjunction with prednisolone, after failure of standard therapy. Clinical remission occurred rapidly in both dogs after commencement of enrofloxacin and in one case where repeat colonoscopy was performed the endoscopic appearance of the mucosa was normal within 2 weeks. Histological examination of the colonic mucosa in this dog after 7 months showed resolution of the cellular infiltration characteristic of histiocytic ulcerative colitis. Histological improvement following therapy in Boxer dogs with histiocytic ulcerative colitis has not been reported previously. [source] Obesity, bariatric surgery and type 2 diabetes,a systematic reviewDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2004Cynthia V. Ferchak Abstract Obesity is endemic in the United States and is closely linked to the development of type 2 diabetes. Both obesity and diabetes are responsible for significant morbidity and mortality. Likewise, both conditions are resistant to treatment. Recent studies have evaluated prevention of type 2 diabetes through intensive lifestyle intervention, while others are examining the impact of bariatric surgery on type 2 diabetes. This article presents an overview of the impact of bariatric surgical and lifestyle interventions on the prevention and treatment of type 2 diabetes. Although studies using a variety of bariatric surgical techniques are included, the focus is on two interventions in particular: the Roux-en-Y gastric bypass and the laparoscopic silicone gastric banding procedure. Outcomes of these procedures are further contrasted with recent lifestyle intervention studies, in particular, the Diabetes Prevention Program study. Gastric bypass studies have been associated with a 99 to 100% prevention of diabetes in patients with IGT and an 80 to 90% clinical resolution of diagnosed early type 2 diabetes. Gastric banding procedures are associated with a lower median (50,60%) clinical remission of type 2 diabetes. Lifestyle intervention studies of obese and glucose-intolerant patients have achieved a 50% reduction in the progression of IGT to diabetes over the short term, with no reported resolution of the disease. Weight loss by any means in the obese patient appears to prevent progression to type 2 diabetes, at least in the short term. Furthermore, sustained weight loss through bariatric surgical intervention is associated both with prevention of progression of IGT and with clinical remission of early type 2 diabetes. Copyright © 2004 John Wiley & Sons, Ltd. [source] MAGNIFYING COLONOSCOPY FOR THE DIAGNOSIS OF INFLAMMATORY CHANGES IN ULCERATIVE COLITISDIGESTIVE ENDOSCOPY, Issue 3 2006Satoshi Sugano Background:, Endoscopic observation is the most effective method for the evaluation of staging in ulcerative colitis (UC). However, in cases with very mild inflammatory activity, histopathological diagnosis may also be required. Unfortunately, biopsy-related accidents are not uncommon. As an alternative, we have used a magnifying colonoscope commonly used for tumor diagnosis to examine in detail the colon mucosa of UC patients in clinical remission, and then compared these findings relative to conventional endoscopy using histopathological diagnosis. Subjects and Methods:, Among UC cases examined by colonoscopy between April 2000 and April 2005, 27 cases without hematochezia for at least 1 month were enrolled in this study. Following observations of inflammatory changes using conventional colonoscopy, magnifying observation and biopsies at a total of 144 sites were evaluated. Using histopathological standards, acute-phase inflammation was indicated by the presence of neutrophil infiltration, whereas chronic-phase inflammation was indicated by infiltration of lymphocytes, plasma cells and eosinophils. Results:, Indicators of significant inflammation by conventional observation was erosion. Under magnification, inflammation appears as superficial defects in mucosa and small whitish spots. When the presence of infiltrating neutrophils was used as a positive histological marker for inflammation, there was no difference in the accuracy of diagnosis by conventional observation (95.1%) versus magnifying observation (97.2%). In contrast, when lymphocyte infiltration was used as a marker, the accuracy of diagnosis increased significantly (88.2%) using magnifying observation relative to conventional observation (61.1%). Conclusions:, Magnifying endoscopy can be used effectively in the evaluation of minute mucosal changes in cases of UC remission. [source] Long-term follow-up of achalasic patients treated with botulinum toxinDISEASES OF THE ESOPHAGUS, Issue 2 2000D'Onofrio Botulinum toxin A (BoTx), a potent inhibitor of acetylcholine release from nerve endings both within the myenteric plexus and at the nerve,muscle junction, has been shown to decrease the lower esophageal sphincter (LES) pressure in patients with achalasia. Because of this property, the esophageal injection of BoTx has been suggested as an alternative treatment in achalasia. The objective of this study was to determine the long-term efficacy and safety of intrasphincteric injection of BoTx in a group of achalasic patients. Nineteen patients (mean age 56.1 ± 19.2 years) were enrolled in the study. All of them were injected endoscopically with 100 U of BoTx by sclerotherapy needle at different sites of the LES. Symptom score (dysphagia, regurgitation and chest pain, each on a 0,3 scale), esophageal manometer and esophageal radionuclide emptying were assessed before the treatment and at 4 weeks, 3 months and 1 year after BoTx injection. In case of failure or relapse (symptom score >2), the treatment was repeated. All but five patients (74%) were in clinical remission at 1 month. Mean symptom score after 1 month of BoTx decreased from 7.1 ± 0.9 to 2.2 ± 2.5 (p < 0.05). LES pressure decreased from 38.4 ± 13.7 to 27.4 ± 13.5 mmHg (p < 0.05) and 10-min radionuclide retention decreased from 70.9 ± 20.7% to 33.8 ± 27.0% (p < 0.05). Side-effects (transient chest pain) were mild and infrequent. At 12 months, the clinical score was 0.9 ± 0.5 (p < 0.05 vs. basal); mean LES pressure was 22.0 ± 7.1 (p < 0.05 vs. basal) and 10-min radionuclide retention was 15.8 ± 6.0% (p < 0.05 vs. basal). The efficacy of the first injection of BoTx lasted for a mean period of 9 months (range 2,14 months). At the time of writing (follow-up period mean 17.6 months, range 2,31), 14 patients (10 with one injection) were still in remission (74%). Our results showed that one or two intrasphincteric injections of BoTx resulted in clinical and objective improvement in about 74% of achalasic patients and are not associated with serious adverse effects; the efficacy of BoTx treatment was long lasting; this procedure could be considered an attractive treatment, especially in elderly patients who are poor candidates for more invasive procedures. [source] Effects of a MAPK p38 inhibitor on lung function and airway inflammation in equine recurrent airway obstructionEQUINE VETERINARY JOURNAL, Issue 6 2008J.-P. LAVOIE Summary Reasons for performing study: It has been suggested that many of the beneficial effects of corticosteroids are mediated through mitogen-activated protein kinase (MAPK) p38 inhibition. Objective: To investigate the efficacy of the MAPK p38 inhibitor compound MRL-EQ1 to either prevent (Phase 1) or treat (Phase 2) recurrent airway obstruction (RAO) in horses. Methods: MRL-EQ1 was administered i.v. at a dosage of 0.75-1.5 mg/kg bwt q. 12 h. In Phase 1, susceptible horses in clinical remission were divided into 2 groups (n = 5/group), based on historical values of respiratory mechanics. All horses were entered in the study in pairs (one control, one treated horse) and exposed to the same environmental challenge (stabling, mouldy hay and dusty conditions). The treatment group received MRL-EQ1 for 14 days while the control horses were untreated during the same period. In Phase 2, affected horses were ranked by severity of respiratory dysfunction and split randomly into either dexamethasone or MRL-EQ1 treatment groups (n = 5/group). Bronchoalveolar lavage fluid, respiratory mechanic measurements, MRL-EQ1 plasma concentration and tumour necrosis factor (TNF) whole blood activity were evaluated sequentially. Results: In Phase 1, MRL-EQ1 did not prevent the occurrence of clinical signs and pulmonary inflammation. However, treatment was associated with a reduction in severity and a delay in the onset of signs and a reduction in pulmonary neutrophilia. In Phase 2, plasma concentrations achieved resulted in ex vivo suppression of lipopolysaccharide-induced TNF production in equine blood. MRL-EQ1 did not improve airway inflammation or lung function and was associated in a dose dependent manner with behavioural (depression, excitability) and blood changes (neutrophilia, increased serum muscle enzyme concentrations). Conclusions: Inhibition of p38 in the horse was partially effective in reducing clinical signs and airway inflammation when administered prior to, but not during clinical exacerbation in RAO. Potential relevance: Inhibitors of p38 MAPK with a better toxicity profile may be effective in the prevention or treatment of RAO. [source] Qualitative and quantitative evaluation of equine respiratory mechanics by impulse oscillometryEQUINE VETERINARY JOURNAL, Issue 1 2006E. VAN ERCK Summary Reasons for performing study: The long- established conventional reference technique (CRT) for measuring respiratory mechanics in horses lacks sensitivity and there is a need for further refinement in new technology, such as the impulse oscillometry system (IOS). Objectives: To evaluate the potential use of the IOS as a clinical respiratory function test and compare it to the current CRT in horses suffering from common upper and lower airway dysfunctions. Methods: Six healthy horses were tested before and after induction of a unilateral nasal obstruction (UNO) or transient left laryngeal hemiplegia (LLH). Six heaves-affected horses were tested in clinical remission and during a heaves crisis, before and after nebulisation of cumulative doses of a bronchodilator therapy (ipratropium bromide; IPB). Results: As opposed to the CRT, the IOS was able to detect partial upper airway obstruction (UAO) caused by UNO or LLH in resting horses, without differentiating both conditions. Upper airway obstruction caused an upward shift of resistance (Rrs) from 5 to 35 Hz without altering reactance (Xrs). As for the CRT, IOS respiratory parameters measured in heaves-affected horses in crisis differed significantly from values measured during remission. The difference in frequency-dependent behaviour of Rrs and Xrs allowed discrimination between upper and lower airway obstructions. Bronchodilator treatment induced significant dose-dependent changes in Xrs at 5 and 10 Hz, from the first dose. Total pulmonary resistance (RL) and Rrs at 5 Hz were affected from the second dose and displayed similar sensitivity. Although post treatment RL values were comparable to remission, Rrs and Xrs remained significantly different, characterising persistent peripheral obstruction. Conclusions: The IOS was more sensitive than the CRT in detecting partial UAO in resting horses and persistent post treatment peripheral dysfunction in heaves-affected horses. The IOS is a sensitive test that provides graded quantitative and qualitative information on disease-induced respiratory dysfunctions as well as on treatment efficiency in horses. Potential relevance: The IOS could represent a practical and sensitive alternative respiratory function test for routine clinical investigations of common airway obstructive diseases and therapy in horses. [source] Environment and prednisone interactions in the treatment of recurrent airway obstruction (heaves)EQUINE VETERINARY JOURNAL, Issue 5 2000C. A. Jackson Summary Recurrent airway obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional benefit. Twelve RAO-susceptible horses were stabled, fed hay, and bedded on straw until they developed airway obstruction. At this point, bedding was changed to wood shavings and they were fed a pelleted diet for 2 weeks. Lung function was measured and bronchoalveolar lavage was performed before and 3, 7, and 14 days after environmental modification. In a crossover design, horses were treated for the 14 days with prednisone tablets (2.2 mg/kg bwt, q. 24 h). Horses then returned to pasture for 30 days. Airway obstruction was greatest before environmental modification. Significant improvement in lung function occurred within 3 days of the change in environment and continued to Day 7. Airway function was best after 30 days at pasture. The clinical response achieved by environmental modification was not significantly improved by addition of oral prednisone. The total number of cells, total neutrophils, and percent neutrophils was greatest before environmental modification. In the absence of prednisone, total and percent neutrophils did not decrease until Day 14 and total cell number until 30 days at pasture. In the presence of prednisone, total cells and total and percent neutrophils decreased by Day 3 and again at pasture. The fact that lung function can be improved within 3 days by environmental management alone emphasises the need for allergen reduction as the cornerstone of treatment of RAO. Although prednisone induced a more rapid reduction in airway inflammation, this was not associated with a more rapid improvement in airway function. [source] Research Submission: Mixture Analysis of Age at Onset in Migraine Without Aura: Evidence for Three SubgroupsHEADACHE, Issue 8 2010Carlo Asuni MD (Headache 2010;50:1313-1319) Objective. , To verify the presence of different age at onset (AAO) subgroups of patients in a sample of patients with migraine without aura (MWA) and compare clinical correlates among them. Background., MWA is a long-lasting disease whose prognosis has not yet been fully investigated. Patients may present complete remission, partial clinical remission, persistence and progression (migraine attack frequency and disability may increase over time leading to chronic migraine). Limited evidence exists regarding the identification of risk factors or predictors which might influence migraine prognosis. AAO has been proven a useful tool in the investigation of the clinical, biological, and genetic characteristics able to influence the prognosis of a number of neuropsychiatric disorders. AAO distribution was studied using mixture analysis, a statistical approach that breaks down the empirical AAO distribution observed into a mixture of normal components. Methods., A sample of 334 outpatients affected by MWA, recruited in a clinical genetic study at our Headache Center from 2004 to 2008, was enrolled for this study. Diagnosis was made according to International Headache Society criteria 2004. AAO distribution in patients was studied using mixture analysis. Chi-square test was used to compare clinical correlates among identified subgroups. Logistic regression was performed in order to correct for effect of possible confounders. Results., Mixture analysis broke up the observed distribution of AAO into 3 normal theoretical distributions. Informational criteria clearly showed a better 3-component model rather than the 2-component one. An early-onset (,7 years of age), an intermediate-onset (,8 and ,22), and a late-onset group (,23) were identified. Comparison of clinical correlates among subgroups by means of chi-square test showed a statistically significant result for migraine frequency (,2 = 7.41, P = .02). Considering the frequency of migraine attacks as a main outcome, the regression model showed a higher AAO is associated with low frequency (odds ratio = 0.95; P = .02). Conclusions., The significant association between AAO and attack frequency found in our study supports the hypothesis that AAO could act as a predictor factor able to influence prognosis. AAO could represent a phenotype suitable for identifying MWA susceptibility genes. [source] Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeuticsIMMUNOLOGICAL REVIEWS, Issue 1 2008Marc Feldmann Summary: Advances in cDNA and monoclonal antibody technology in the 1980s fuelled the discovery and characterization of the properties of cytokines. It became apparent that because cytokines were expressed in tissues derived from autoimmune diseases, they were likely to be of fundamental importance in disease pathogenesis and developing a new class of biological therapeutics. In this review, we describe the history of bench to bedside translation of work that led to the identification of tumor necrosis factor (TNF) as a key regulator of the loss of homeostatic immune-inflammatory responses in rheumatoid arthritis (RA) and a good therapeutic target. First in human clinical trials in collaboration with a biotechnology company, the safety and efficacy of TNF blockade with a chimeric monoclonal antibody was substantiated in patients refractory to standard anti-rheumatoid drugs. Abnormal immune-inflammatory responses after therapy showed improvement and remain a focus of ongoing research in many laboratories. Longer term multi-center studies that followed with several anti-TNF biologicals have demonstrated the augmented efficacy, including inducing clinical remission, of low dose methotrexate and anti-TNF therapy co-therapy, but serious infections and lymphomas in a low frequency have been observed. In the course of the past decades, three ,blockbuster' anti-TNF biologicals are in the clinic. Over a million patients with RA and other immune-mediated diseases have been successfully treated, and a better perspective on the risk of harm and its management has become part of good clinical practice. This success has encouraged a burgeoning industry of biologicals for chronic diseases. [source] Efficacy of infliximab in pediatric Crohn's disease: A randomized multicenter open-label trial comparing scheduled to on demand maintenance therapyINFLAMMATORY BOWEL DISEASES, Issue 3 2009Frank M. Ruemmele MD Abstract Background: Infliximab (IFX) is efficacious in inducing remission in severe forms of pediatric Crohn's disease (CD). Adult studies indicate that IFX is also safe and well tolerated as maintenance therapy. The present study aimed to evaluate in a prospective manner the efficacy and safety of IFX as maintenance therapy of severe pediatric CD comparing scheduled and "on demand" treatment strategies. Methods: Forty children with CD (nonpenetrating, nonstricturing as well as penetrating forms, mean age: 13.9 ± 2.2 years) with a severe flare-up (Harvey,Bradshaw Index [HBI] ,5, erythrocyte sedimentation rate [ESR] >20 mm/h) despite well-conducted immunomodulator therapy (n = 36 azathioprine, n = 1 mercaptopurine, n = 3 methotrexate) combined with steroids were included in this randomized, multicenter, open-label study. Three IFX infusions (5 mg/kg) were administered at week (W)0/W2/W6. At W10, clinical remission (HBI <5) and steroid withdrawal were analyzed and IFX responders were randomized to maintenance therapy over 1 year: group A, scheduled every 2 months; group B, "on demand" on relapse. Results: In all, 34/40 children came into remission during IFX induction therapy (HBI: 6.7 ± 2.5 (WO) vs. 1.1 ± 1.5 (W10); P < 0.001). At the end of phase 2, 15/18 (83%) patients were in remission in group A compared to 8/13 (61%) children in group B (P < 0.01), with a mean HBI of 0.5 versus 3.2 points (group A versus B, P = 0.011). In group A, 3/13 (23.1%) children experienced a relapse compared to 11/12 (92%) children in group B. No severe adverse event occurred during this trial. Conclusions: IFX is well tolerated and safe as maintenance therapy for pediatric CD, with a clear advantage when used on a scheduled 2-month basis compared to an "on demand" basis. (Inflamm Bowel Dis 2009) [source] Oral budesonide for the therapy of post-liver transplant de novo inflammatory bowel disease: A case series and systematic review of the literatureINFLAMMATORY BOWEL DISEASES, Issue 12 2008A. Sidney Barritt IV MD Abstract Background: The therapy for posttransplant IBD is clinically challenging. Patients receiving liver transplants are immunosuppressed to prevent rejection, but via an unknown mechanism develop de novo IBD in spite of receiving some of the same medications used for therapy in traditional IBD. In the published literature most of the patients who developed de novo IBD were treated with traditional corticosteroids. Exposure to systemic corticosteroids increases risks of infection, diabetes mellitus, and osteoporosis among other complications. Budesonide, a luminally active steroid with low systemic absorption, is an established therapeutic agent for IBD that should receive special considerations as first-line therapy in this patient population. Methods: We describe 3 cases of de novo IBD after liver transplantation. None of these patients had a history of IBD prior to their transplant. All 3 were treated with oral budesonide in lieu of systemic corticosteroids. Additionally, a Medline MeSH search was performed using the terms "inflammatory bowel disease" and "liver transplant" as part of a systematic review of the literature. Results: All 3 cases of de novo post transplant IBD went into clinical remission with oral budesonide. The Medline search ultimately revealed 19 case reports, case series or retrospective reviews on de novo post liver transplant IBD. Most reports focused on the diagnosis and risk factors and did not have an emphasis on therapy. Conclusions: Given the track record for budesonide in traditional IBD, and its documented efficacy and systemic steroid-sparing benefit, in our opinion this drug should be considered first-line therapy for de novo posttransplant IBD. (Inflamm Bowel Dis 2008) [source] Sarcopenia is prevalent in patients with Crohn's disease in clinical remissionINFLAMMATORY BOWEL DISEASES, Issue 11 2008Stéphane M. Schneider MD Abstract Background: Patients with Crohn's disease (CD) are prone to osteoporosis. A loss of muscle mass, called sarcopenia, is responsible for an increased risk of disability. Many factors associated with osteopenia also decrease muscle mass. The aim of the present study was to measure the prevalence of sarcopenia in CD patients in remission and uncover its relationship with osteopenia. Methods: In all, 82 CD patients (43 female / 39 male; 36 ± 14 years; body mass index [BMI] 21.1 ± 3.4) and 50 healthy volunteers (30F/20M; 39 ± 13 years; BMI 22.2 ± 2.5) were studied. Body composition was assessed using dual-energy x-ray absorptiometry. Sarcopenia was defined as an appendicular skeletal muscle index (ASMI) below 5.45 kg/m2 for women and 7.26 for men. Osteopenia was defined as a T-score for bone mineral density (BMD) (g/cm2) below ,1.0. Results: In all, 60% of CD patients were found to be sarcopenic and 30% osteopenic, compared to 16% and 4% of controls, respectively (P < 0.01). ASMI was significantly lower in patients than in controls (6.0 ± 1.1 versus 6.5 ± 1.2; P < 0.05). Sarcopenic patients had significantly (P < 0.01) lower BMI (20.0 ± 3.5 versus 22.7 ± 2.8 kg/m2), lean mass (41.5 ± 9.1 versus 48.1 ± 9.1 kg), and BMD (1.09 ± 0.12 versus 1.15 ± 0.08 g/cm2) than nonsarcopenic patients; 91% of sarcopenic patients were also osteopenic. ASMI correlated with BMD (r = 0.46; P < 0.01) and BMI (r = 0.38; P < 0.01). Conclusions: The prevalence of sarcopenia is high in young CD patients and strongly related to osteopenia. These 2 phenomena may share similar mechanisms. Simultaneous screening for sarcopenia and osteopenia may be useful in CD patients. (Inflamm Bowel Dis 2008) [source] Fecal calprotectin is useful in predicting disease relapse in pediatric inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 5 2008Dorota Walkiewicz MD Abstract Background: Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker to determine the degree of intestinal inflammation and predicting relapse in patients with inflammatory bowel disease (IBD). The aim was to compare FC levels in IBD and healthy controls, to correlate FC levels with clinical disease activity, and to assess whether FC levels can be used to predict clinical relapse in children with IBD. Methods: Enzyme-linked immunosorbent assay (ELISA) determined levels of FC were measured in more than 1 stool samples (n) from 32 IBD patients (n = 97) and from 34 healthy controls (n = 37). Disease activity was assessed by the Harvey,Bradshaw index in Crohn's disease (CD) and by Physician's Global Assessment (PGA) in both CD and ulcerative colitis (UC). Clinical events were recorded up to 9 months following stool collection in CD patients. Wilcoxon rank sum test and Fisher's exact tests were used to compare FC levels in IBD patients and in control. Kaplan,Meyer analysis was used to determine a risk of clinical relapse in relation to FC levels. Results: The IBD group had higher FC levels (range 17,7500 g/g) compared with control (16,750 g/g, P < 0.0001). FC levels were higher during relapse (CD, 3214 ± 2186; UC, 2819 ± 1610) compared to remission (CD, 1373 ± 1630; UC, 764 ± 869; P < 0.0001). Among those with clinical relapse, 90% had FC levels more than 400 ,g/g in CD. Eighty-nine percent of CD encounters with FC levels less than 400 ,g/g remained in clinical remission. Conclusions: FC levels differentiate active IBD from controls. Among children with CD and in remission, FC levels may be useful in predicting impending clinical relapse. (Inflamm Bowel Dis 2008) [source] MDR1 polymorphisms and response to azathioprine therapy in patients with Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 5 2007Juan L. Mendoza MD Abstract Background: To investigate the contribution of multidrug resistance 1 (MDR1) gene pharmacogenetics (G2677T/A and C3435T) to the efficacy of azathioprine in inducing remission in patients with Crohn's disease (CD). Methods: A cohort of 327 unrelated Spanish patients with CD recruited from a single center was studied. All patients were rigorously followed up for at least 2 years (mean time, 11.5 years). A case-control analysis of MDR1 G2677T/A and C3435T SNPs and 2 loci haplotypes in 112 steroid-dependent CD patients treated with azathioprine was performed. Patients were classified on the basis of response to azathioprine. Results: A total 76 patients treated with azathioprine for longer than 3 months were included. Remission was achieved in 42 CD patients (55.3%). A higher frequency of the 2677TT genotype was found in nonresponders than in responders (17.65% versus 7.14%; OR = 2.8; 95% CI; 0.6,12.1; P = 0.11). Nonresponders to azathioprine were found to have a higher frequency of the 3435TT genotype than did CD patients who had achieved clinical remission (17.64% versus 4.76%; OR = 4.3; 95% CI, 0.8,22.8; P = 0.06). The 2677T/3435T haplotype was also more abundant in nonresponders (29.4% versus 20.2%), whereas the 2677G/3435C haplotype was more frequent in responders (58.3% versus 47.1%). Lack of response to azathioprine therapy in CD patients was 1.8-fold greater in carriers of the 2677T/3435T haplotype than in carriers of the 2677G/3435C haplotype (OR = 1.8; 95% CI, 0.82,3.9; P = 0.14). Conclusions: The results of our study indicate higher frequencies of the 2677TT and 3435TT genotypes and the 2677T/3435T haplotype in CD patients who did not respond to azathioprine. Additional replications in independent populations would confirm the real impact of these polymorphisms in response to azathioprine therapy. (Inflamm Bowel Dis 2007) [source] Oral mesalamine and clinical remission are associated with a decrease in the extent of long-standing ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 7 2006Michael F. Picco MD Abstract Objective: To compare colonoscopy alone with surveillance biopsy for the determination of anatomic extent in long-standing ulcerative colitis (UC). To assess the influences of mesalamine use and clinical disease activity on the change of histologic extent with time. Materials and Methods: Disease extent (proctosigmoiditis, left-sided colitis, or pancolitis) measured by colonoscopy and surveillance biopsy was compared among 212 consecutive patients with long-standing UC. Among the 102 patients who had 2 consecutive colonoscopies with surveillance biopsies, the following influences on change in histologic extent were determined: disease activity, mesalamine use, age at disease onset, folic acid, corticosteroid and azathioprine/6-mercaptopurine use, and time between colonoscopies. Results: Agreement between gross and microscopic findings was poor (, = 0.39). Colonoscopy underestimated and overestimated extent in 25.9% and 8.5%, respectively. Microscopic distribution between consecutive colonoscopies remained the same in 60.8%. Where distribution changed, an increase was twice as common as a decrease in extent. There was no difference in age at onset, time between colonoscopies, or disease duration among those with an increase, decrease, or no change in extent. Clinical remission and oral mesalamine were independently associated with 10.7 and 5.8 times the odds of a decrease in disease extent, respectively. Folic acid, topical mesalamine, corticosteroids, and immunomodulators did not influence change in extent. Conclusions: UC extent is best determined by surveillance biopsy. Among patients with long-standing UC, histologic extent fluctuates with time. Disease remission and oral mesalamine were independently associated with decreases in disease extent. [source] 5-Aminosalicylate therapy is associated with higher 6-thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprineINFLAMMATORY BOWEL DISEASES, Issue 4 2006Scott Hande MD Abstract Background: Small uncontrolled trials have suggested that 5-aminosalicylate (5-ASA) medications increase 6-thioguanine nucleotide (6-TGn) levels in adults with Crohn's disease (CD) on azathioprine (AZA) or 6-mercaptopurine (6-MP), presumably through the inhibition of thiopurine methyltransferase (TPMT). We tested the theory that coadministration of 5-ASA agents with AZA/6-MP results in higher 6-TGn levels in a large cohort of children and adults with CD or ulcerative colitis (UC). Methods: A retrospective cohort study identified all children and adults treated for IBD with AZA/6-MP at 2 tertiary medical centers. Patients were included if their TPMT genotype was known and 6-TGn and 6-methymercaptopurine (6-MMP) levels had been obtained after 3 months of clinical remission at a stable dose of AZA/6-MP. 6-TGn and 6-MMP levels were compared between patients taking and those not taking 5-ASA medications through the use of linear regression models to identify and adjust for potentially confounding variables. Results: Of the 126 patients included, 88 were taking 5-ASA medications. Patients on 5-ASA agents had higher mean 6-TGn levels after adjustment for confounding variables (,6-TGn, 47.6 ± 21.8 pmol/8 × 108 red blood cells; P = 0.03). CD and TPMT heterozygosity was independently associated with higher 6-TGn levels (P = 0.01 and P = 0.03, respectively). 5-ASA exposure was not associated with a change in 6-MMP levels. Conclusions: We found that 5-ASA therapy is associated with higher 6-TGn levels in children and adults with IBD on 6-MP/AZA. TPMT inhibition may not explain this effect because 5-ASA exposure did not affect 6-MMP levels. The observed association of CD with higher 6-TGn levels is novel and needs to be verified in prospective studies. [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] A new oral delivery system for 5-ASA: Preliminary clinical findings for MMxINFLAMMATORY BOWEL DISEASES, Issue 5 2005Cosimo Prantera MD Abstract Background: Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how the therapy would compare with topical 5-ASA. Methods: Patients received either 1.2 g of 5-ASA MMx three times per day plus placebo enema or 4 g of 5-ASA enema plus placebo tablets for 8 weeks. The primary endpoint was clinical remission (clinical activity index ,4) at 8 weeks. Secondary endpoints were endoscopic and histologic remissions. Results: Seventy-nine patients were enrolled. Clinical remission rates at 4 and 8 weeks were 57.5% and 60.0% for patients treated with MMx and 68.4% and 50.0% for patients randomized to 5-ASA enemas, respectively (95% confidence interval for the difference at 8 weeks, ,12 to +32). Endoscopic remission was achieved by 45.0% of patients on 5-ASA MMx and by 36.8% of those on enema, whereas 15.0% and 8% of patients, respectively, showed histologic remission. Compliance was 97.0% for oral and 87.5% for topical therapy. In the enema group, compliance was 88.0% for the patients in remission and 65.5% for those with active disease. Conclusions: Preliminary studies suggest that similar rates for induction of remission can be expected from 5-ASA enemas and MMx for patients with left-sided ulcerative colitis. [source] Muscle performance in patients with Crohn's disease in clinical remissionINFLAMMATORY BOWEL DISEASES, Issue 3 2005Jean-Baptiste Wiroth PhD Abstract Background: Because patients with Crohn's disease (CD) often show increased energy expenditure, nutritional deficiencies, and general fatigue, all which may persist after a flare, we hypothesized that CD could alter muscle mass and function. This study aimed to assess muscle strength and endurance in CD patients in clinical remission and the influencing factors. Methods: Forty-one outpatients (17 men and 24 women; age, 37 ± 10 yr), in remission (CD Activity Index < 150) for >3 months, and 25 age-matched healthy controls (10 men and 15 women; age, 37 ± 13 yr) were evaluated. Evaluation included a sit-up test, hand-grip strength test, hand-grip endurance test, lower limb strength test, and lower limb endurance test (LE), as well as a measure of physical activity. Results: No significant difference was found between CD and control groups regarding weight, height, body mass index, fat mass, and fat-free mass. Strength performance was lower in CD subjects compared with controls, particularly for lower limb indexes: lower limb strength test (,24.6%, P < 0.001), LE (,25.8%, P < 0.001), and sit-up test (,25.1%, P < 0.001). Previous disease severity, disease duration, the cumulative dose of glucocorticosteroids, current inflammation, and global habitual physical activity did not affect muscle performance. A recent use of steroids improved LE. Conclusions: CD patients in clinical remission have decreased muscle function that may affect their quality of life. This pattern is reflected by reduced strength and endurance indexes, particularly for lower limbs. The reasons for these changes need further study. Strength training should be assessed in these patients. [source] Shortened questionnaire on quality of life for inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2004M. J. Alcalá MD Abstract Questionnaires for measuring quality of life in patients with inflammatory bowel disease usually include a large number of items and are time-consuming for both administration and interpretation. Our aim was to elaborate and validate a short quality-of-life questionnaire with the most representative items from the Spanish version of the 36-item Inflammatory Bowel Disease Questionnaire (IBDQ-36) using the Rasch analysis. The responses to 311 IBDQ-36 questionnaires from 167 patients with ulcerative colitis (UC) and 144 with Crohn's disease (CD) were analyzed. IBDQ-36 was shortened with successive Rasch analyses until all the remaining items showed acceptable separation and goodness-of-fit properties. Validation of the short questionnaire was studied in a new group of 125 patients by determining its validity and reliability. A 9-item short questionnaire was obtained (IBDQ-9). Its correlation with IBDQ-36 was excellent (r = 0.91). Correlation between IBDQ-9 and clinical indices of activity was statistically significant in UC (r = 0.70) and CD (r = 0.70). IBDQ-9 score discriminates adequately between patients in clinical remission or relapse (P < 0.01). Sensitivity to change was determined in 14 patients who improved clinically, showing significant IBDQ-9 changes between both determinations (P < 0.01), with an effect size of ,2.67 in UC and ,5.29 in CD. IBDQ-9 was also homogeneous, with a Cronbach's , of 0.95 in UC and 0.91 in CD. In 35-clinically stable patients, test-retest reliability was good, with a statistically-significant correlation between both questionnaires (r = 0.76 in UC and 0.86 in CD, P < 0.01) and an intraclass correlation coefficient of 0.82 in UC and 0.84 in CD. In conclusion, a short and valid questionnaire to measure quality of life in patients with inflammatory bowel disease was obtained using a new measurement model. Its use should facilitate comprehension of the impact of inflammatory bowel disease. [source] Leflunomide in subacute cutaneous lupus erythematosus , two sides of a coinINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2008Anke Suess MD Background, Subacute cutaneous lupus erythematosus (SCLE), a distinct clinical subset of lupus erythematosus, remains a therapeutic challenge, especially in cases resistant to topical and standard systemic therapy. Leflunomide, a novel antirheumatic drug, has shown efficacy in the treatment of systemic lupus erythematosus in pilot studies. Methods, We report two patients with SCLE who demonstrated the spectrum of possible clinical responses to leflunomide therapy. Results, One patient experienced a complete clinical remission of symptoms, whereas the other developed a massive skin reaction which was distinctly related to the commencement of leflunomide therapy. Conclusion, To our knowledge, this is the first time that remission and deterioration of SCLE by leflunomide therapy have been described. [source] Treatment of refractory fludarabine induced autoimmune haemolytic with the anti-cd20 monoclonal antibody rituximabINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2006R. SWORDS Summary A patient with cold-type autoimmune haemolytic anaemia for 8 years developed progressive B cell chronic lymphocytic leukaemia (CLL). Despite the risk of fludarabine induced exacerbation of haemolysis, he was given aggressive anti-CLL therapy with six courses of FCR (fludarabine 25 mg/m2 D1,3, cyclophosphamide 250 mg/m2 D2,4 and rituximab 375 mg/m2 D1) every 4 weeks. This resulted in a marked acute increase in haemolysis shortly after completing each course of fludarabine. However, haemolysis had settled to its baseline level by the time of subsequent courses of FCR. FCR resulted in complete clinical remission of CLL but residual haemolysis persisted. The patient was then given four weekly infusions of single agent rituximab, resulting in ongoing remission of haemolysis. In this patient, rituximab appears to have controlled fludarabine induced exacerbation of autoimmune haemolysis. In addition, subsequent single agent rituximab therapy resulted in prolonged remission of cold-type autioimmune haemolytic anaemia. It remains to be seen if the addition of rituximab will allow other patients with a positive direct Coomb's test and/or autoimmune haemolysis to receive fludarabine containing chemotherapy without undue risk of life-threatening haemolytic anaemia. [source] Laboratory findings associated with thrombophilia are not more common in inflammatory bowel diseaseINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2000K. K. Sundaram Summary Thromboembolic disease (TED) has been recognized as a complication of inflammatory bowel disease (IBD) since the 1930s ( Bargen & Barker 1936). The relative contributions of inherited or acquired thrombophilia and the inflammatory response to the mechanism of this tendency is unclear. Thrombotic events are more common in active disease although significant numbers also occur spontaneously, when the disease is in clinical remission ( Talbot et al. 1986 ; Jackson et al. 1997 ). Studies looking at the prevalence of specific thrombophilic states such as Antithrombin III deficiency ( Jackson et al. 1997 ; Lake, Stauffer & Stuart 1978; Cianco et al. 1996 ; Ghosh et al. 1983 ), Factor V Leiden mutation (APC Resistance) ( Jackson et al. 1997 ; Probert et al. 1997 ; Ardizzone et al. 1998 ; Liebman et al. 1998 ), anticardiolipin antibodies ( Ciancio et al. 1996 ), Protein C ( Wyshock, Caldwell & Crowley 1988; Korsten & Reis 1992) and Protein S deficiencies ( Jorens et al. 1990 ; Aadland et al. 1992 ) in IBD have been contradictory or equivocal. We had previously found that IBD patients with a history of TED are not more likely to have a laboratory thrombophilic abnormality than those with uncomplicated disease. We also demonstrated that the prevalence of heterogenous laboratory thrombophilic abnormalities (usually minor) in all IBD patients may be as high as 60%, much higher than the recognized prevalence of TED ( Lim, Jones & Gould 1996). We wondered how this would compare with the healthy non-IBD population. We have therefore explored the prevalence of such thrombophilic abnormalities in a group of IBD patients who had no history of TED and compared them with healthy age and sex matched controls. [source] | ||||||||||||||||||||||||||||||||||