Association of the macrophage migration inhibitory factor gene polymorphisms with inflammatory bowel disease.
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Biomedical subjects
Publications and source records attributed to J L Mendoza.
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BACKGROUND AND OBJECTIVES: Interleukin-10 (IL-10) has a key role in regulating mucosal inflammation in inflammatory bowel disease. In our population of Spanish ulcerative colitis (UC) patients, we have previously demonstrated that two polymorphisms (IL-10.G14 microsatellite allele and homozygous for the -1082G allele (guanine at position -1082)) in the IL-10 gene were susceptibility markers for disease. No data exist regarding the relationship of these IL-10 polymorphisms with phenotypic subpopulations in UC. Therefore, this study sought to examine the contribution of IL-10 polymorphisms to phenotypical variability in UC. MATERIAL AND METHODS: A cohort of 215 Spanish unrelated patients with UC recruited in a single center was studied. All patients were rigorously phenotyped and followed for at least 3 years (mean time: 11.8 years). The clinical phenotype was established before genotyping. Genotyping was performed using polymerase chain reaction (PCR) assays. RESULTS: Patients with UC included 129 (60%) men and 89 (40%) women. Mean age at diagnosis was 38 years, with a range of 8-83. Disease extent included 127 (59.1%) left-side patients and 88 (40.9%) extensive patients. Neither UC phenotype variable was associated with the presence of susceptibility polymorphisms (10G14 microsatellite and -1082G allele). CONCLUSIONS: In Madrid's Spanish population of UC patients, the carrying of the ILG14 microsatellite or -1082G polymorphism in the IL-10 gene was not associated with phenotype of disease.
Treatment of perianal fistulas in Crohn's disease should be defined on an individual basis. A combined medical and surgical approach is the optimal treatment. Adequate management of perianal fistula disease is based on the presence or absence of active proctitis, anatomic location, and fistula type. Furthermore, the presence of perianal abscesses must be ruled out. This evaluation includes digital rectal examination, endoscopy, and examination under anesthesia combined with pelvic magnetic resonance imaging or anorectal endoscopy ultrasonography findings.
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OBJECTIVE: To evaluate the efficacy and toxicity of infliximab for the treatment of fistulizing Crohn's disease. METHODS: Consecutive patients with fistulizing Crohn's disease receiving infliximab were prospectively enrolled. Partial response was defined as a reduction of 50% or more from base-line in the number of draining fistulae. Complete response was defined as the closure of all fistulae. The influence of different variables on the efficacy of infliximab was evaluated. RESULTS: 108 patients were included. The disease was inflammatory plus fistulizing in 18% and only fistulizing in 82%. After the third infusion of infliximab the response was partial in 26% and complete in 57%. Response (%) rates (partial/complete) depending on fistula location were: enterocutaneous (25/68%), perianal (35/60%), rectovaginal (36/64%), and enterovesical (20/40%). None of the studied variables (including concomitant immunosuppressive therapy) correlated with efficacy of infliximab in the multivariate analysis. Incidence of adverse effects (21%) depending on the dose of infliximab was: first dose (5.6%), second (7.4%), and third (11.1%). CONCLUSIONS: Infliximab is an efficacious treatment for fistulizing Crohn's disease. Partial response was achieved in approximately one third of the patients, and complete response in more than half. No studied variable was predictive of response. Adverse effects were relatively infrequent and mild.
OBJECTIVE: To describe our experience with granulocyte apheresis to induce remission in patients with active Crohn's disease refractory to conventional treatment. We summarize the results previously obtained with this technique. CONCLUSIONS: Granulocyte apheresis is a safe and well tolerated therapeutic modality that can be a valid therapeutic alternative in the induction of remission in inflammatory bowel disease, although controlled clinical trials must be conducted to define long-term efficacy, as well as to establish "optimal patient" selection, re-treatment interval, and number of sessions.
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BACKGROUND: We assessed the prevalence of R702W, G908R, and L1007fs coding mutations in the NOD2/CARD15 gene and the genotype-phenotype relation in Spanish patients with Crohn disease. METHODS: A cohort of 204 unrelated patients with Crohn disease and 140 healthy controls were studied. The phenotype was established before commencement of genotyping. Genotyping of the R702W, G908R, and L1007fs gene polymorphisms of NOD2/CARD15 was performed by two independent laboratories using different techniques. In the case of discordant results, specific sequencing of DNA strands was performed. RESULTS: At least one mutation was present in 32.8% of patients compared to 10.7% in controls (OR = 4.08, 95% CI 2.21 to 7.50). In patients with Crohn disease, the frequency of R702W, G908R, and L1007fs carriers was 13.7%, 8.3%, and 14.2%, respectively. Compound heterozygotes and homozygotes occurred in 3.4% and 2.9% of patients and in none of the controls. The correlation of genotype-Vienna classification showed a significant association with ileal disease (RR = 1.61, 95% CI 1.21-2.15, P = 0.001) and an inverse association with colonic localization (RR = 0.29, 95% CI 0.11-0.80, P = 0.007). There was a significant association between G908R carriership and previous appendectomy, surgical interventions, and stricturing behavior. A gene-dosage effect on phenotypic characteristics was not observed. CONCLUSIONS: In a Spanish population from Madrid, mutations of the NOD2/CARD15 gene were a marker of susceptibility to Crohn disease and were associated with ileal disease. Carriers of the G908R mutation showed a stricturing disease behavior, history of appendectomy, and surgical interventions over the course of the disease.
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UNLABELLED: The inflammatory bowel disease is accompanied by cutaneous manifestations in approximately 10% of the cases. Neutrophilic dermatoses are located on the dermis and/or epidermis and are characterised on histological examination by the presence of an infiltrate that consists largely of neutrophils. The prototype of neutrophilic dematoses is Sweetacute;s syndrome; which is rarely associated with Crohńs disease. CASE REPORT: A 63 year old woman was admitted to hospital with pyrexia, abdominal pain, episcleritis and skin lesions. She presented erythematous lesions on trunk, legs and arms, with tendency towards formation of plaques, nodules and vesicular pustular lesions. Both the colonoscopy and colonic biopsies confirmed the diagnosis of colonic Crohńs disease. Cutaneous biopsies re-vealed an infiltrate consisting mainly of neutrophils. These biopsies, together with clinical details led to the diagnosis of Sweetacute;s syndrome. A methylprednisolone treatment rapidly improved the skin lesions and clinical symptoms. The different clinical forms of neutrophilic dermatosis are an extra intestinal manifestation of Crohńs disease, and are some-times found concurrently in the same patient, which would indicate a common pathogenesis with different clinical presentations (spectrum of neutrophilic dermatoses).
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OBJECTIVE: The aim of this study is to report our experience with infliximab and analyse prognostic factors for response in Crohn's disease (CD). MATERIAL AND METHODS: Consecutive patients were prospectively enrolled in the study when referred for infliximab infusion. Data collected included indication for infusion, patient epidemiological characteristics, Vienna classification, previous surgery, previous medications and extra-intestinal manifestations. Adverse events and clinical response were tabulated separately for patients with luminal or fistulous Crohn's disease. RESULTS: 28 patients were treated (7 with inflammatory and 21 with fistulizing disease). Patients received a total of 116 infusions of infliximab: 57.1% (4 of 7) of patients with luminal disease had complete response within a median of 17.5 days (range 15-28 days), and 62% (13 of 21) of patients with fistulizing disease had complete response within a median of 9 days (range 6-51 days). All patients (5) without relapse received concomitant treatment with immune modifiers. The group of patients with previous resection or perianal fistula repair had complete response more frequently p = 0.03 (OR = 30; IC 95% = 1.47-119.8). CONCLUSIONS: Infliximab is safe and beneficial in clinical practice for Crohn's disease. The re-treatment regimen of infliximab is effective in maintaining clinical response. Immunosuppressant therapy may have a role in the duration of maintained clinical remission in patients with fistulizing disease. In patients with perianal fistulizing disease infliximab treatment is more effective when previous resection or fistula repair is present.
BACKGROUND: The benefit of highly active antiretroviral therapy (HAART) may be limited by the development of liver toxicity. The prevalence and risk factors of this complication using different antiretroviral drug combinations are not well known. PATIENTS AND METHOD: Clinical charts of HIV-infected patients, previously naive for antiretroviral drugs, starting HAART between January 1997 and January 2000 were reviewed. Liver toxicity was scored according to increases in liver enzymes. RESULTS: HIV infection had been acquired by intravenous drug use in 36 (40%) of 91 subjects recruited in the study. The rest had been infected through homosexual (38%) or heterosexual contact (22%). Overall, 43 patients (47%) were coinfected with hepatitis C (42%) and/or B (8%) viruses. Antiretroviral therapy included protease inhibitors (PI) plus two nucleosides in 48 individuals and non-nucleosides in 50. Baseline characteristics were similar across the different treatment groups. Liver toxicity was recorded in 30 (31%) subjects, and it was severe in 10 (11%). Cytolysis was the predominant pattern (28), while only one case of cholestasis and one with a mixed pattern were recorded. Coinfection with hepatitis B and/or C viruses was associated with liver toxicity (RR: 10.36; 95% CI, 1.38-77.56; p = 0.03) as was a high alcohol intake (RR: 3.35; 95% CI, 2.43-4.62; p = 0.01). No differences in the rate of hepatotoxicity were found when comparing PI and non-nucleoside containing regimens. The development of isolated hyperbilirubinemia (27%) was strongly associated with the use of indinavir (RR: 3.61; 95% CI, 1.81-7.21; p < 0.001). CONCLUSIONS: Liver toxicity occurs in about one third of HIV-infected patients after initiating HAART, regardless of the drugs used, yet it is commonly mild and transient. A high alcohol intake and a coinfection with HCV/HBV constitute the most important predictive factors.
OBJECTIVES: Treatment of HIV infection with highly antiretroviral therapy (HAART) may be limited by liver toxicity. Its incidence and risk factors are not well known. PATIENTS AND METHODS: Retrospective chart review. Naive patients beginning HAART between January 1997 and January 2000. Severe transaminase elevation was defined as fivefold or higher rise over upper normal limits, or as > or =3.5-fold rise above abnormal baseline values. RESULTS: Of 222 study subjects, 38%, 5%, and 2% were coinfected with hepatitis C virus (HCV), hepatitis B virus, and hepatitis D virus, respectively. Besides two nucleoside reverse transcriptase inhibitors (NRTIs), 96 patients received protease inhibitors (PIs), 90 received nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 35 received a PI + NNRTI combination. Severe hepatic injury developed in 21 (9%): 10% PI, 9%, and 9% PI + NNRTI. Both univariate and multivariate analyses identified alcohol abuse, HCV coinfection, and older age as independent risk factors. Predictor variables in the final multivariate model were: alcohol abuse (risk ratio [RR], 5.87; 95% confidence interval [CI], 1.49-23.15; p =.01], positive HCV serology (RR, 3.99; 95% CI, 1.32-12.10; p =.01], and older age (RR, 1.11; 95% CI, 1.04-1.18; p = 0.001). CONCLUSIONS: Nearly 10% of study subjects who start HAART experience severe transaminase elevation, irrespective of the treatment. Avoidance of alcohol abuse, especially in study subjects coinfected with HCV, will reduce the risk of hepatic injury after HAART. When possible, prior treatment for chronic HCV infection should be considered.