Serum transforming growth factor-beta1 levels increase in response to successful anti-inflammatory therapy in ulcerative colitis.

OBJECTIVE: To investigate serum levels of transforming growth factor-beta1 and interferon-gamma in active ulcerative colitis and to assess changes during treatment. METHODS: We prospectively evaluated serum from 25 patients with untreated active ulcerative colitis and 19 healthy controls. Disease activity score (DAI), serum transforming growth factor-beta1 and interferon-gamma levels were measured at baseline and after 7 days of conventional treatment. Disease activity score and transforming growth factor-beta1 were also assessed at 42 days. RESULTS: Baseline transforming growth factor-beta1 levels were significantly higher in patients than in controls (P < 0.02). On the 7th day, transforming growth factor-beta1 levels increased only in patients who responded (P < 0. 01); variations in transforming growth factor-beta1 levels and disease activity score were inversely correlated (r=- 0.72, P < 0. 001). At day 42, serum transforming growth factor-beta1 decreased significantly compared with the 7th day (P < 0.05). While in controls, interferon-gamma was undetectable; untreated patients had higher, widely variable, levels. At day 7, responders had higher interferon-gamma values than unresponsive cases. Variations in interferon-gamma correlated moderately with changes in transforming growth factor-beta1 (r=0.53, P < 0.05). Cytokine response did not depend upon the type of treatment. CONCLUSIONS: Both transforming growth factor-beta1 and interferon-gamma may play a role in the injury-repair process in active ulcerative colitis. Variations in circulating transforming growth factor-beta1 levels in the first week of treatment seem to be related to the therapeutic response.

Budesonide enema in pouchitis--a double-blind, double-dummy, controlled trial.

BACKGROUND: Pouchitis has been suggested to be a recurrence of ulcerative colitis in a colon-like mucosa. Topical steroids are a valid therapeutic alternative for distal forms of ulcerative colitis. AIM: To investigate the efficacy and tolerability of budesonide enema in the treatment of pouchitis compared with oral metronidazole. MATERIALS AND METHODS: Twenty-six patients with an active episode of pouchitis (defined as a pouchitis disease activity index score >or= 7) and no treatment during the previous month were randomized to receive either budesonide enema (2 mg/100 mL at bedtime) plus placebo tablets or oral metronidazole (0.5 g b.d.) plus placebo enema in a prospective, double-blind, double-dummy, 6-week, controlled trial. RESULTS: Based on the intention-to-treat principle, we detected a significant improvement in disease activity at the end of the first week with both drugs (P < 0.01). After that, improvement was moderated until stabilization at 4 weeks in both treatments. The per protocol analysis showed that both drugs had similar efficacy in terms of disease activity, clinical and endoscopic findings. Fifty-eight per cent and 50% of patients improved (decrease in pouchitis disease activity index >or= 3) with budesonide enema and metronidazole, respectively (odds ratio, 1.4; confidence interval, 0.2-8.9). Adverse effects were observed in 57% of patients given metronidazole and in 25% of patients given budesonide. CONCLUSIONS: Budesonide enemas are an alternative treatment for active pouchitis, with similar efficacy but better tolerability than oral metronidazole.

[Synchronous lesions in advanced colorectal cancer]. / Lesiones sincrónicas en el cáncer colorrectal avanzado.

From jan '82 to jun '91 were done 3701 colonoscopic procedures. Of these, we arrived to cecum in 283 patients (pat) (51.1%) (male: 175 pat; female: 108 pat) in the first six months after the diagnostic of the colorectal cancer (CRC). The localization of the primary CRC was: rectum: 17.7%; left colon: 37.8% and right colon: 44.5%. 105 synchronical polyps (p) were seen in 87 pat (30.7%): 61 pat with 1p; 16 pat with 2 p and 10 pat with 3 p. Adenomas: 50/105 p (56.19%). Early cancer was histologically confirmed in 11/105 p (11/59 p adenomas). The distribution of early were 5/11 in the same colon segment ant 6/11 in the different colon segment. 1 pat has 3 early cancer. Synchronic advanced colorectal cancer (ACC) was seen in 9 pat (M/F = 2/1). All of these in different segments. In conclusion, the high frequency of the premalignant (adenomas) an malignant (early and advanced cancer) lesions, and the high risk of these in different segments of the large bowel, shows the colonoscopy is the most efficient method in the detection of the synchronical lesions of the colorectal cancer.

Time course of nitric oxide synthase generation after gluten exposure in the rectal mucosa of gluten-sensitive patients.

BACKGROUND: Nitric oxide is thought to play an important role in modulating chronic inflammatory responses as well as in immune-mediated inflammation. We reproduced a gluten-mediated mucosal response in the rectum of celiac and control subjects in order to determine the role of inducible and constitutive nitric oxide synthases in the pathogenesis of this process. MATERIAL: Nine patients with confirmed celiac disease and five healthy controls underwent a long-term rectal gluten challenge (48 h) after an enema of 6 g of crude gluten, and constitutive and inducible nitric oxide synthase activity were determined in rectal biopsies. The histological localization of inducible nitric oxide synthase was determined by immunohistochemistry. RESULTS: Activity of both isoforms of nitric oxide synthase in control subjects did not change significantly after gluten instillation. In celiac patients, constitutive nitric oxide synthase on rectal mucosa also showed no significant changes after challenge with gluten. Inducible nitric oxide synthase isoform exhibited a modest increase 4 h after gluten instillation in celiac patients (mean increase 35% compared with baseline levels) but, 8 h after challenge, generation of iNO synthase was significantly higher: 54% more than pre-challenge production (P < 0.05) and higher than control values (P < 0.05). Inducible nitric oxide synthase staining was mostly localized in mononuclear cells of the epithelium and the lamina propria. After gluten instillation, the enhanced staining was mainly localized in subepithelial areas of the lamina propria. CONCLUSION: Our data suggest a role for nitric oxide, generated by inducible nitric oxide synthase, in the process of rectal mucosa injury by local gluten instillation in sensitized patients. We could not, however, determine if the role of nitric oxide in the ensuing injury of this gluten-induced immune inflammation model is a protective one, or merely a by-product generated by the activation of the inflammatory cells.

Gluten sensitivity in the rectal mucosa of first-degree relatives of celiac disease patients.

BACKGROUND/AIMS: Rectal gluten challenge is a simple, sensitive, and specific test of mucosal gluten sensitivity. Our aims in this study were to evaluate gluten sensitivity in a group of relatives of celiac patients and to compare these findings with those obtained on small bowel histology, celiac disease-related serology, and HLA typing. METHODS: A 4-h rectal gluten challenge was performed with 6 g of crude gluten in saline solution in 29 first-degree relatives, 20 well-diagnosed celiac patients, and 10 subjects in whom celiac disease had been excluded. The number of intraepithelial lymphocytes in pre- and postchallenge frozen rectal biopsies (pan T-cell immunocytochemistry) was quantified by computerized image analysis. RESULTS: The intraepithelial lymphocyte response after gluten instillation was significantly higher in celiac disease patients (median, 126% increase above the baseline count; 95% confidence interval: 61-213%) compared with control subjects (median, -5%; 95% confidence interval: -29-5%). Using a cut-off of 20% change in intraepithelial lymphocyte count, 14 relatives (48%) showed a celiac-like response. Two of these subjects had partial villous atrophy and increased lymphocyte counts in the small bowel mucosa. One of them also exhibited a positive celiac disease-related serology and the typical celiac human lymphocyte antibody (HLA) DQ2. The remaining 12, and all those relatives with a negative challenge, had normal small bowel mucosa and were negative for antigliadin and endomysial antibodies. The characteristic celiac HLA (DQA1 0501 DQB1 0201 heterodimer) was identified in five relatives with positive challenge (including the patient with more severe mucosal atrophy) but was also present in eight relatives with no evidence of gluten sensitivity in the rectal mucosa. CONCLUSIONS: Our study characterizes a subgroup of relatives of celiac patients who show mucosal evidence of sensitization after local instillation of gluten in the rectum but who have no other features of celiac disease.

Gluten sensitivity in patients with primary biliary cirrhosis.

OBJECTIVE: Whereas celiac disease and primary biliary cirrhosis have been reported to coexist in the same patient, the frequency of this relationship has not been clarified. Nowadays, the concept of celiac disease has been extended from that of a severe enteropathy to a broader concept of gluten-driven intestinal immunological response. In this study we assessed features of gluten sensitivity in a cohort of patients with primary biliary cirrhosis. METHODS: Ten patients with primary biliary cirrhosis were evaluated a mean of 2 yr after diagnosis. The following features of gluten sensitivity were assessed: serum antigliadin and endomysial antibodies, small bowel histology (degree of atrophy and quantitative histological parameters), the presence of the typical celiac HLA genotype (DQ2), and intraepithelial lymphocyte response in the rectal mucosa after local gluten instillation (rectal gluten challenge). RESULTS: Overall, three patients presented evidence of gluten sensitivity. All three had abnormal titers of antigliadin antibody type IgA and one was positive for endomysial antibody. Two patients had partial villous atrophy. The rectal gluten challenge showed a celiac-like response, evidenced by an increase in intraepithelial lymphocyte infiltration after gluten exposure, in the three patients. The characteristic celiac HLA genotypes (DQA1 0501 and DQB1 0201) were identified in three patients. One of them also exhibited other features of gluten sensitivity. However, despite evidence of gluten intolerance, patients had minimal or no symptoms characteristic of celiac disease. CONCLUSION: We detected features of gluten sensitivity in a high proportion of patients with primary biliary cirrhosis. Further studies should be performed to elucidate the clinical significance of this association.

Lesiones sincrónicas en el cáncer colorrectal avanzado / Synchronous lesions in the advanced colorectal cancer

Desde ene'82 a jun'91 fueron realizados 3701 fibrocolonoscopía, diagnosticándose cáncer colorrectal (CCR) en 554 pacientes (pac.). De ellos, se llegó a ciego en 283 pac (51,1// ) (Masc: 175 pac; Fem: 108 pac) ya sea en el momento del diagnóstico o dentro de los 6 primeros meses posteriores a la cirugía. La distribución de pólipos sincrónicos (p) en 87 pac (30,7//) = 61 pac. tuvieron 1p; 16 pac, 2p; y 10 pac, 3p. En total: 105 p. Adenomas: 59/105p. 11/105p representaron carcinoma temprano, hsitológicamente confirmado (representando 11/59 adenomas). La distribución de los mismos fue: 5/11 en el mismo segmento colorrectal; 6/11 en diferentes segmento. 1pac. tuvo 3 carcinomas tempranos. Cáncer colorrectal avanzado sincrónico fue presentado por 9 pac (Masc./Fem = 2/1). Todos ellos localizados en distinto segmento colorrectal que el tumor primario. En conclusión, la alta frecuencia de presentación de lesiones premalignas (adenomas) y malignas (cáncer temprano y/o avanzado), y el alto riesgo de presentación de las mismas en diferentes segmentos que el tumor primario, muestra a la colonoscopía como el método más eficiente en la detección ( y eventual extracción) de lesiones sincrónicas del cáncer colorrectal