Pharmacologic therapy for inflammatory bowel disease refractory to steroids.

Although corticosteroids are an effective treatment for induction of remission in inflammatory bowel disease (IBD), many patients are dependent on or refractory to corticosteroids. This review is based on scrutinizing current literature with emphasis on randomized controlled trials, meta-analyses, and Cochrane reviews on the management of IBD refractory to corticosteroids. Based on this evidence, we propose algorithms and optimization strategies for use of immunomodulator and biologic therapy in IBD refractory to corticosteroids.

Enema de tacrolimus para el tratamiento de la enfermedad inflamatoria intestinal / Tacrolimus enema for the treatment of Inflammatory Bowel Disease

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Hyperhomocysteinemia and methylenetetrahydrofolate reductase 677C-->T and 1298A-->C mutations in patients with inflammatory bowel disease.

BACKGROUND: Hyperhomocysteinemia has been recently described in patients with inflammatory bowel disease (IBD), that could be related to the increased risk for thrombosis that exists in this disease. The aim of this study was the assessment of hyperhomocysteinemia in patients with IBD and its relation among vitamin B12 and folate levels, and methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C mutations. PATIENTS AND METHODS: Fifty two consecutive patients with IBD were studied (29 women and 23 men); age: mean (standard deviation 41.7 [11.9] years) and 186 controls with no difference in age and gender. Hyperhomocysteinemia was considered as homocysteine levels higher than mean plus two standard deviations of the control group (> or = 13 micromol/l). RESULTS: patients had an elevated prevalence of hyperhomocysteinemia (17.3 vs. 3.7%; p = 0.002) and lower folate (7.6 [4.1] vs. 8.9 [3.7] ng/ml; p = 0.01) and B12 vitamin levels (499 [287] vs. 603 [231] pg/ml; p = 0.003). Homocysteinemia was higher (14.3 [5.8] vs. 9.1 [3.9] micromol/l; p = 0.006) in 6 patients (11.5%) that had suffered thromboembolism. Frequency of MTHFR 677C-->T (13.5 vs. 11.3%; p = 0.66) and 1298A-->C (7.8 vs. 7.0%; p = 0.76) mutations was not increased in patients. Odds ratio (OR) for IBD in hyperhomocysteinemic patient was 5.51, 95% confidence interval (CI), 1.81-16.76; p = 0.002). Hyperhomocysteinemia was negatively associated with feminine gender (OR 0.08, 95% CI 0.01-0.49; p = 0.006) and folate levels (OR 0.04, 95%CI: 0.007-0.20; p < 0.001). CONCLUSIONS: hyperhomocysteinemia is associated with IBD and low folate levels, and could be involved in development of thromboembolism. MTHFR 677C-->T and 1298A-->C mutations are not related with the disease.

Hiperhomocisteinemia y mutaciones de la metilentetrahidrofolato reductasa 677C→ T y 1298A→ C en pacientes con enfermedad inflamatoria intestinal / Hyperhomocysteinemia and methylenetetrahydrofolate reductase 677→T and 1298A→ mutations in patients with inflammatory bowel disease

Fundamento: recientemente se ha descrito la existencia de hiperhomocisteinemia en la enfermedad inflamatoria intestinal(EII), que podría estar relacionada con el mayor riesgo de trombosisen esta enfermedad. El objetivo del estudio ha sido evaluar la hiperhomocisteinemia en los pacientes con EII y su relación con las concentraciones de vitamina B12 y folato séricos y con las mutacionesde la metilentetrahidrofolato reductasa (MTHFR)677C→T y 1298A→C.Pacientes y métodos: se estudiaron consecutivamente 52 pacientes con EII (29 mujeres y 23 varones; edad: media [desviación estándar] 41,7 [11,9] años) y 186 controles con edad y sexo similares. Se consideró hiperhomocisteinemia cuando los valoresde homocisteína eran superiores a la media más dos desviacionesestándar del grupo control (≥ 13 µmol/l).Resultados: los pacientes presentaban una mayor prevalenciade hiperhomocisteinemia (17,3 frente a 3,7%; p = 0,002) yunos valores más bajos de folato (7,6 [4,1] frente a 8,9 [3,7]ng/ml; p = 0,01) y de vitamina B12 (499 [287] frente a 603 [231]pg/ml; p = 0,003). En 6 pacientes (11,5%) que habían padecidoepisodios tromboembólicos la homocisteinemia era más elevada(14,3 [5,8] frente a 9,1 [3,9] µmol/l; p = 0,006). La frecuenciade las mutaciones MTHFR 677C→T (13,5% frente a 11,3%; p= 0,66) y de la 1298A→C (7,8 frente a 7,0%; p=0,76) no fuemayor en los pacientes. La odds ratio (OR) de EII en los pacienteshiperhomocisteinémicos fue 5,51, intervalo de confianza [IC]del 95%: 1,81-16,76; (p = 0,002). La hiperhomocisteinemia seasoció negativamente con el sexo femenino (OR 0,08, IC del95%, 0,01-0,49; p = 0,006) y con los valores de folato (OR0,04,IC del 95%: 0,007-0,20; p < 0,001).Conclusiones: la hiperhomocisteinemia se asocia a la EII y alas concentraciones bajas de folato, y puede estar implicada en eldesarrollo de tromboembolia. Las mutaciones MTHFR 677C→ Ty 1298A→ C no se relacionan con la enfermedad

Background: hyperhomocysteinemia has been recently describedin patients with inflammatory bowel disease (IBD), thatcould be related to the increased risk for thrombosis that exists inthis disease. The aim of this study was the assessment of hyperhomocysteinemiain patients with IBD and its relation among vitaminB12 and folate levels, and methylenetetrahydrofolate reductase(MTHFR) 677C→ T and 1298A→C mutations.Patients and methods: fifty two consecutive patients withIBD were studied (29 women and 23 men); age: mean (standarddeviation 41.7 [11.9] years) and 186 controls with no differencein age and gender. Hyperhomocysteinemia was considered as homocysteinelevels higher than mean plus two standard deviationsof the control group (≥ 13 µmol/l).Results: patients had an elevated prevalence of hyperhomocysteinemia(17.3 vs. 3.7%; p = 0.002) and lower folate (7.6[4.1] vs. 8.9 [3.7] ng/ml; p = 0.01) and B12 vitamin levels (499[287] vs. 603 [231] pg/ml; p = 0.003). Homocysteinemia washigher (14.3 [5.8] vs. 9.1 [3.9] µmol/l; p = 0.006) in 6 patients(11.5%) that had suffered thromboembolism. Frequency of MTHFR677C→T (13.5 vs. 11.3%; p = 0.66) and 1298A→C (7.8 vs.7.0%; p = 0.76) mutations was not increased in patients. Odds ratio(OR) for IBD in hyperhomocysteinemic patient was 5.51, 95%confidence interval (CI), 1.81-16.76; p = 0.002). Hyperhomocysteinemiawas negatively associated with feminine gender (OR0.08, 95% CI 0.01-0.49; p = 0.006) and folate levels (OR 0.04,95%CI: 0.007-0.20; p < 0.001).Conclusions: hyperhomocysteinemia is associated with IBDand low folate levels, and could be involved in development ofthromboembolism. MTHFR 677C→T and 1298A→C mutationsare not related with the disease

Los inmunosupresores en el tratamiento de la enfermedad inflamatoria intestinal / Immunosuppresive therapy for inflammatory bowel disease

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[Non alcoholic steatohepatitis. Mid-term clinical and histologic course in 10 patients]. / Esteatohepatitis no alcohólica. Evolución clínica e histológica a medio plazo de diez pacientes.

BACKGROUND: The progressive character of the hepatic lesions in nonalcoholic steatohepatitis (NASH) has not been well established. In the present study, the clinical and histological course of this condition was evaluated at medium term. METHODS: Then patients (6 females and 4 males) with NASH, in a non-cirrhotic stage at the time of diagnosis, were followed up during 58 +/- 7 months (range 24 to 88 months). RESULTS: Nine patients were obese, but a significant reduction of body weight was found at the end of the study (p = 0.0072). Other clinical, physical or laboratory changes were not found, although in two cases hepatic biochemical tests were within normal limits when the follow-up biopsy was performed. Changes in the characteristic hepatic features were also absent, although fat infiltrates disappeared in three cases. Six patients had increased fibrosis and a progression of the hepatic architectural distortion; four reached the stage of cirrhosis. The evolution of the hepatic lesion correlated with the interval between diagnostic and follow-up biopsies (r = 0.69; p less than 0.05) and with the reduction in body weight (r = 0.64; p less than 0.05). CONCLUSIONS: In most cases, NASH results in a progressive hepatic distortion with can end in cirrhosis, although the change is slow and silent.