Biomedical subjects
J Belaiche
Publications and source records attributed to J Belaiche.
Extensive ulcerative colitis and extraintestinal manifestations in a patient with HIV infection and significant CD4 T-cell lymphopenia.
We report a heterosexual patient with HIV infection and a CD4 T-cell count of 0.45 x 10(9)/L who developed mild ulcerative proctitis, sacroileitis and oligoarthiritis. While he was treated with 5-aminosalicylic enemas, the patient rapidly developed severe pancolitis. An emergency colectomy without procetectomy was performed. A few months later, he suffered recurrence of ulcerative proctitis, aggravation of arthritic pain and developed anterior uveitis. All symptoms disappeared after proctectomy. There was no evidence for opportunistic infection or Kaposi's sarcoma. Antineutrophil cytoplasmic antibodies were positive and the HLA-B27 antigen was present. CD4 counts were lower during the phases of active disease than during remission. This case demonstrates that severe ulcerative colitis can occur in the presence of moderate T-cell defects. In view of a recent report of remission of Crohn's disease under comparable circumstances, it is possible that the extent of T-cell involvement in both diseases is radically different.
Placebo-controlled clinical trial of mesalazine in the prevention of early endoscopic recurrences after resection for Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID).
OBJECTIVE: Endoscopic postoperative recurrences occur early after 'curative' surgery for Crohn's disease. Pentasa has been shown to be effective in the maintenance treatment of quiescent Crohn's disease. The aim of this study was to test the efficacy of a 12-week oral intake of Claversal in the prevention of endoscopic recurrences after 'curative' resection for ileal, colonic or ileocolonic Crohn's disease. We conducted a multicentre double-blind controlled trial comparing Claversal (1g tid) with placebo, starting within 15 days after surgery. The macroscopic normality of the two anastomotic segments was assessed at surgery. Patients were clinically and biologically evaluated twice (6-week interval), and colonoscopy was performed at 12 weeks. Endoscopic relapse was defined by any anastomotic ulcerations or stenosis and staged according to a four-grade score. RESULTS: Between May 1989 and May 1991 12 centres included 126 patients, 70 women and 56 men, aged 33 +/- 12 years (range 16-70) in the study. Disease locations were ileal, colonic and ileocolonic in 45, 6 and 49%, respectively. Claversal and placebo groups were similar at inclusion, except for ESR (37 +/- 26 vs. 27 +/- 23 mm/h in the Claversal and placebo groups, respectively; P < 0.05). Nine patients were withdrawn from the study. Adverse reactions occurred only in six patients. Five patients were excluded for protocol violation. Finally, 106 patients could be evaluated at 12 weeks (55 Claversal and 51 placebo). An endoscopic relapse was observed in 50% and 63% of the Claversal and placebo groups, respectively (P = 0.16), with a similar grade distribution. Claversal was well tolerated. CONCLUSIONS: Our study confirms that a large proportion of endoscopic recurrences occur within 3 months of resection in Crohn's disease. There was a slight trend towards greater efficacy of Claversal; it could be worthwhile trying higher dosages and/or 5-ASA compounds with different intestinal release profiles.
Decrease in systemic tolerance to fed ovalbumin in indomethacin-treated mice.
The oral administration of non-steroidal anti-inflammatory drugs (NSAID) to animals induces a quick increase in intestinal permeability and secondary inflammatory lesions of the intestine. The mechanisms leading to the inflammatory lesions are hypothetical. The increased intestinal permeability could allow a greater mucosal and systemic penetration of fed antigens and bacterial products leading to an abnormal mucosal and systemic immune and inflammatory response toward these materials. We examined the effect of oral dosing with indomethacin on ovalbumin serum levels and the systemic immune response to ovalbumin in mice fed with ovalbumin. The ovalbumin serum level was higher in indomethacin-treated mice and the increase was proportional to the dose of indomethacin. It was associated with epithelial and subepithelial lesions. Moreover, the systemic humoral and, to a lesser extent, the cellular tolerance were partially abrogated in the treated mice. These findings suggest that the oral administration of indomethacin in mice induces an increased passage of fed antigen through the intestinal epithelium associated with a decrease in systemic tolerance to this antigen. The reason for this decrease remains unclear. Besides a disequilibrium between systemic and mucosal immune responses, a loss of integrity of the intestinal epithelial cells and a direct immunomodulating effect of indomethacin may also be involved. This decrease in systemic tolerance to luminal antigen could be involved in the development of NSAID enteropathy.
[Clinical case of the month. Hereditary hemochromatosis].
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[How I explore.... The small intestine using double-lumen enteroscopy].
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[H2 inhibitors and protein pump inhibitors].
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Soluble interleukin-2 receptor in Crohn's disease. Assessment of disease activity and prediction of relapse.
In Crohn's disease, the activity of the disease is difficult to evaluate and the evolution of the disease is difficult to predict. The soluble interleukin-2 receptor serum level has been reported to correlate with clinical activity of the disease and with mucosal immune activation. We compared serum soluble interleukin-2 receptor to classical inflammatory markers and other immune parameters in the assessment of clinical disease activity and prediction of relapse in patients with Crohn's disease. Soluble interleukin-2 receptor serum levels correlated well with the Crohn's disease activity index, and multivariate analysis showed that this correlation was independent of the other inflammatory and immune markers. The correlation was not greater, However, than that between some inflammatory markers, such as ESR, and Crohn's disease activity index. Longitudinal follow-up showed that a high soluble interleukin-2 receptor serum level was highly predictive of relapse. Multivariate analysis showed that the soluble interleukin-2 recepteur serum level was complementary to other inflammatory and clinical markers in the prediction of relapse of disease. We conclude that soluble interleukin-2 receptor is of use in monitoring Crohn's disease, particularly in prediction of relapse.
Comparison of budesonide and 5-aminosalicylic acid enemas in active distal ulcerative colitis.
BACKGROUND: Budesonide is a new corticosteroid with high topical anti-inflammatory activity but little systemic effect. The aim of the present study was to compare the efficacy and safety of budesonide enema (2 mg/100 mL) and 5-ASA enema (mesalazine 1 g/100 mL) given for 4 weeks in the treatment of active distal ulcerative colitis and proctitis. METHODS: Ninety-seven patients were studied in a multicentre single-blind randomized group-comparative trial. The primary efficacy variables were endoscopy and histopathology scores obtained at 0, 2 and 4 weeks. Clinical symptoms were the secondary efficacy variables. Haematology, chemistry and adverse events were the safety variables. RESULTS: Budesonide and 5-ASA enemas both resulted in a significant improvement in endoscopy and histopathology scores but no difference could be demonstrated between the two treatment groups. There was also a significant improvement of symptoms (number of bowel movements per day, quality of stools, presence of blood and mucus, and state of well-being) within both groups but no difference between the two treatment groups. The clinical remission rate at 4 weeks was, however, 38% for patients treated with budesonide enema but 60% for those treated with 5-ASA enema (P = 0.03). No adverse events attributed to the study drugs were recorded in either of the groups. CONCLUSIONS: Budesonide enema 2 mg/100 mL appears to be as efficient and well-tolerated as 5-ASA enema in the treatment of active distal ulcerative colitis and proctitis.
Increased frequency of bronchial hyperresponsiveness in patients with inflammatory bowel disease.
Although bronchopulmonary manifestations are rare in inflammatory bowel disease (IBD), subclinical abnormalities have been described in up to 50% of cases. The pathophysiology of these abnormalities remains unknown. However, a latent inflammation of the bronchial mucosa secondary to the inflammation of the intestinal mucosa has been suggested. This subclinical inflammation may lead to increased bronchial responsiveness. We studied the bronchial responsiveness in 38 inflammatory bowel disease (IBD) patients, using the methacholine test. Bronchial hyperresponsiveness was defined by a PC20M < 16 mg/ml. Twenty-four healthy controls were also studied. There was no significant difference in baseline FEV1 between IBD patients and controls. However, there was a significantly greater fall in FEV1 in the IBD patients at the concentrations of methacholine tested. The frequency of bronchial hyperresponsiveness was significantly higher in the IBD population (45%) than in controls (17%; P < 0.03). Atopy, defined by skin test, was more common in IBD patients (42%) than in controls (21%). Even when only nonatopic subjects were considered, the frequency of bronchial hyperresponsiveness was significantly higher in IBD patients (41%) than in controls (5%; P < 0.02). Thus, subclinical bronchial hyperresponsiveness is common in IBD, and may be considered a further extraintestinal manifestation.
Systemic immune response after rectocolonic administration of ovalbumin in mice.
The aim of our study was to determine the effect of a rectocolonic preimmunization with ovalbumin on the systemic immune response induced by a subsequent subcutaneous injection of this antigen in Balb/c mice. One rectocolonic, but not intragastric, administration of 25 mg of ovalbumin induced a detectable increase in serum anti-ovalbumin antibody level. The level reached was however much lower than after subcutaneous injection. Both intragastric and rectocolonic immunization with ovalbumin induced specific systemic cellular tolerance. However, after rectocolonic, but not intragastric, preimmunization there was no systemic humoral tolerance to this antigen. These differences in systemic immune responses after rectocolonic or intragastric administration of ovalbumin could be due to different stimulation of the systemic immune system or to differences between the colonic and small bowel mucosal immune system, which remain to be elucidated.
[Pharmaclinics--how I treat... Crohn disease].
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Deleterious influence of pyrazinamide on the outcome of patients with fulminant or subfulminant liver failure during antituberculous treatment including isoniazid.
Isoniazid and pyrazinamide are well-known hepatotoxic drugs, often used in combination. The aim of this study was to assess the prognostic influence of pyrazinamide on the outcome of fulminant or subfulminant liver failure caused by antituberculous therapy. Eighteen patients with fulminant or subfulminant liver failure due to antituberculous therapy were studied. Nine patients received isoniazid and rifampicin without pyrazinamide (group 1), and nine patients received isoniazid and rifampicin together with pyrazinamide (group 2). The severity of fulminant and subfulminant liver failure, as judged by the prevalence of coma and the lowest level of factor V, was similar in the two groups. Spontaneous survival was greater in group 1 (eight of nine) than in group 2 (two of nine) (P < .02). The authors conclude that pyrazinamide co-administration was associated with an increased mortality in patients with fulminant or subfulminant hepatitis occurring during antituberculous therapy. In these patients, pyrazinamide administration and an interval of more than 15 days between the onset of antituberculous treatment and jaundice, combined with grade III encephalopathy and factor V below 20%, predicted death without liver transplantation.
[Pharma clinics: how I treat... Inflammatory intestinal diseases and pregnancy].
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Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives.
The relationships between clinical activity, endoscopic severity, and biological parameters in Crohn's disease have not been thoroughly investigated and a link was therefore sought between these three elements. The following parameters were determined simultaneously in 121 consecutive patients with colonic or ileocolonic Crohn's disease: Crohn's disease activity index, Crohn's disease endoscopic index of severity, and serum albumin, alpha 2-globulin, alpha 1-antitrypsin, orosomucoid, C reactive protein, erythrocyte sedimentation rate, platelets, lymphocyte and polymorphonuclear cell counts, haematocrit, and faecal alpha 1-antitrypsin concentration. The distribution of these parameters was studied and transformation was used so that data matched the normal distribution closely. A weak but significant correlation (r = 0.32; p < 0.001) was found between clinical and endoscopic indices in the whole group of patients and this correlation seemed to be homogenous in various patient subgroups (clinically quiescent or active disease, pure colonic disease, untreated patients). Endoscopic or clinical indices were also found to be weakly linked with biological parameters (r < 0.50). Stepwise linear regression identified C reactive protein as predictive of the clinical index, and, successively, alpha 2-globulin, erythrocyte sedimentation rate, faecal alpha 1-antitrypsin, serum orosomucoid, and alpha 1-antitrypsin as predictive of the endoscopic index. Both predictions were poor--the biological variables accounting for only 22 and 44% respectively of the clinical and endoscopic index variations. In conclusion, Crohn's disease clinical activity seems to be virtually independent of the severity of the mucosal lesions and biological activity.
[Acute hepatic insufficiency. Diagnosis, treatment and results following orthotopic liver transplantation].
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[Current contribution of genetics in intestinal inflammatory diseases].
It is clear since many years that the liability to develop inflammatory bowel disease is influenced by genetic factors. Recent progresses in the field of genetic markers and genetic models bring the concept of genetic heterogeneity. This new concept leads us to try to classify different forms of inflammatory bowel disease and could have in the future an impact on the prevention, the follow up and the treatment of these diseases.
Insulin secretion, clearance, and action on glucose metabolism in cirrhotic patients.
To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test (0.3 g glucose/kg BW) in nine compensated cirrhotic patients and nine healthy volunteers well matched for age, sex, and body weight. The insulin secretion rate was derived by the deconvolution of plasma C-peptide levels, insulin sensitivity was calculated using Bergman's minimal model method, and insulin clearance was estimated by dividing the 0-180 min area under the curve of insulin secretion rate by that of peripheral plasma insulin levels. The cirrhotic patients were characterized during the frequently sampled i.v. glucose tolerance test by a 60% greater insulin secretion rate (P < 0.05), a markedly reduced insulin sensitivity index (SI; 2.82 +/- 0.75 vs. 5.86 +/- 0.68 x 10(-4) min/mU.L; P < 0.01) and a 40% reduced insulin clearance (725 +/- 169 vs. 1165 +/- 99 mL/min.m-2; P < 0.05). The reduction of insulin clearance was significantly correlated with the amplitude of the portosystemic shunt, measured using an isotopic method (r = 0.75; P < 0.02). In conclusion, cirrhosis is characterized by an important peripheral hyperinsulinism, resulting from both a higher insulin secretion rate and a reduced insulin hepatic clearance; the severe insulin resistance explains the glucose metabolism alterations.