BACKGROUND:T lymphocytes play a crucial role in the pathogenesis of inflammatory bowel disease. Achieving stable T-cell lines, rather than continuous bleeding of patients, is desirable in order to dissect their implication in the disease.METHODS:Long-lasting T-cell lines from patients with Crohn disease and ulcerative colitis and from healthy volunteers have been obtained by transformation of T lymphocytes using the lymphotropic Herpesvirus saimiri. Lines were subjected to phenotypic and functional analyses, and the results compared with freshly isolated peripheral blood mononuclear cells.RESULTS:Fresh cells revealed only minor differences between patients and controls, with regard to phenotype and proliferative capacity. In contrast, the use of T-cell lines showed that cells from Crohn disease patients, but not ulcerative colitis patients, over-responded to several membrane or cytoplasmic stimuli when compared to control T-cell lines. Thus, higher responses were found when stimulated with alphaCD3 and IL2, alphaCD3 and alphaCD28, IL2 alone, phorbol esters (PMA) and alphaCD3 and, finally, PMA and alphaCD2 (P < 0.05 in all instances). Further, lines from patients with Crohn disease responded more vigorously to alphaCD3 and alphaCD28 or alphaCD3 and PMA when compared to ulcerative colitis (P < 0.05 in both instances).CONCLUSIONS:The data obtained with these lines suggest that T cells from patients with Crohn disease differ in vivo in their proliferative capacity, as compared with those from ulcerative colitis patients, a finding that may reflect the clear Th-1 phenotype found in the former and absent in the latter.
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.Objetivo: evaluar la eficacia e identificar los factores predictivos de respuesta al tratamiento con infliximab en la enfermedad de Crohn fistulizante. Métodos: se realizó un estudio prospectivo en pacientes con enfermedad de Crohn fistulizante que recibían tratamiento con infliximab. La respuesta parcial se definió como una reducción del 50% o más de la línea base en el número de fístulas que drenan. La respuesta completa se definió como el cierre de todas las fístulas. Se evaluó la influencia de diferentes variables sobre la eficacia de infliximab. Resultados: se estudiaron 108 pacientes. La enfermedad era inflamatoria y fistulizante en el 18% y sólo fistulizante en el 82%. Después de la tercera infusión de infliximab la respuesta fue parcial en el 26% y completa en el 57%. Las tasas de respuesta (%) (parcial/completa) dependiendo de la localización de la fístula fueron: enterocutánea (25/68%), perianal (35/60%), rectovaginal (36/64%), y enterovesical (20/40%). Ninguna de las variables estudiadas (edad, sexo, tabaco, tratamiento inmunosupresor, antigüedad, origen y localización de la fístula) presentó correlación con la eficacia de infliximab en el análisis de multivariante. La incidencia de efectos adversos (21%) fue: 5,6,7,4 y 11,1% durante la primera, segunda y tercera dosis respectivamente. Conclusiones: infliximab es un tratamiento eficaz para la enfermedad de Crohn fistulizante. Aproximadamente un tercio de los pacientes alcanzaron respuesta parcial y alrededor de la mitad, respuesta completa. Ninguna variable estudiada fue predictiva de respuesta. Los efectos adversos fueron relativamente infrecuentes y leves.
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 determine whether endoscopic signs exist to establish the presence of Helicobacter pylori, which may be used markers of infection in the absence of gastroduodenal peptic lesions.Methods: A prospective study was carried out in 150 consecutive patients, all symptomatic, who presented endoscopic evidence of gastritis and in whom the absence or presence of H. pylori was undetermined at the time of the study. A quantitative assessment was made of the three types of lesions previously associated with the presence of H. pylori on endoscopy: nodules, erosions, and red patches in the antrum, Biopsy samples were taken for the microbiological and histological studies; a positive result in either study was considered to indicate infection by H. pylori.Results: Of the 150 patients studied, 115 (76%) presented H. pylori infection. No significant differences existed with respect to the clinical findings or the distribution according to sex. The mean age of infected patients was 49 years, being lower in the nodular group (p = 0.008) and higher in the group presenting erosions (p < 0.05); this fact suggests that the endoscopic findings may differ depending on the moment of infection.Evidence of antral nodules was observed in 15 patients, 11 of whom (73%) showed positivity for H. pylori; the sensitivity was 9.5% and the positive predictive value was 0.73.Of the 17 patients presenting erosions, 16 were positive for H. pylori (93.8%); the sensitivity was 13% and the positive predictive value was 0.94.Red patches were detected in 63 patients, 48 of whom (76%) were positive for H. pylori; the sensitivity was 48% and the positive predictive value was 0.76.These three patterns did not coincide in any of the patients, for an overall sensitivity and specificity of 70.5% and 80.6%, respectively (p < 0.05).Conclusion: The sensitivity and specificity of the set of lesions assessed were high as no two overlapped; when the lesions were dealt with individually, however, the sensitivity was low, showing a low negative predictive value, making it necessary the use of standard detection measures, althouht in the presence of nodules and/or erosions the existence of H. pylori infection is practically the norm.