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J Belaiche

Publications and source records attributed to J Belaiche.

At least 19 recordsLinked to original sources
PubMed1998

Effects of dexamethasone on the profile of cytokine secretion in human whole blood cell cultures.

EXPERIMENTAL OBJECTIVES: The interaction between the endocrine and immune systems is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the hypothalamo-pituitary-adrenal axis, inhibit the immune and inflammatory responses and are used as immunosuppressive drugs in many inflammatory, autoimmune and allergic diseases. The aims of this study were to investigate the effects of dexamethasone on the profile of cytokine secretion in whole blood cell cultures from healthy subjects and to analyse the gender-related sensitivity to dexamethasone on each cytokine secretion. RESULTS: There was a significant inhibition by dexamethasone (from 1 to 100 nM) on the secretion of monokines (IL-1beta, IL-6, IL-8 and TNF alpha) and lymphokines (IL-2, IL-4, IL-10 and IFN gamma), either after LPS or PHA stimulation (P < 0.01). Interleukin 4 and IL-10 were less inhibited than IFN gamma (P < 0.05 at 1 nM, P < 0.01 at 10 nM and P < 0.001 from 100 nM to 10 microM). No gender difference was observed in the rate of inhibition of the secretion of each cytokine. CONCLUSION: This study shows that the inhibition of cytokine secretion by dexamethasone is more marked on Th1-type cytokines than on Th2-type cytokines. These data support the idea that glucocorticoids may induce a shift from the Th1 to Th2 profile of cytokine secretion.

Adult↗
PubMed1998

Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans.

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals.

Adult↗
PubMed1998

Clinical pattern of corticosteroid dependent Crohn's disease.

OBJECTIVES: Corticosteroid dependency in Crohn's disease (CD) is characterized by the need for chronic use of corticosteroids to maintain clinical remission. Several definitions have been used. Depending on the definition, 10-30% of the patients are considered as corticosteroid dependent. The aim of the study was to define a clinical pattern of corticosteroid dependent CD patients. PATIENTS AND METHODS: Epidemiological and clinical characteristics were retrospectively compared between 20 corticosteroid dependent CD patients and 248 non-corticosteroid dependent CD patients by using univariate and multivariate analyses. Corticosteroid dependency was defined either by two successive relapses during the 2 months after discontinuing glucocorticoids (n=5) or by two successive relapses at dose tapering, after successful treatment of a flare-up by using glucocorticoids (n=15). RESULTS: Corticosteroid dependent CD patients were younger at diagnosis (P < 0.001), and were characterized by a higher frequency of colonic location (P< 0.05), but lower frequency of ileal location (P < 0.01), and higher ano-perineal location (P < 0.05). They were also more frequently smokers (P< 0.05) and users of contraceptive pills (P< 0.01). The inflammatory type of the disease was increased (P < 0.01), while the fibrostenotic type was decreased (P < 0.001) in corticosteroid dependent CD patients. By multivariate analysis, a smoking habit (P < 0.01), a colonic location (P < 0.05), a non-fibrostenotic type (P< 0.05) and a younger age at diagnosis (P< 0.05) were shown to be independently associated with corticosteroid dependency. CONCLUSIONS: This study suggests a clinical pattern associated with corticosteroid dependency. Whether this clinical pattern is simply associated with the dependency, or whether a primary decrease of corticosensitivity produces this clinical pattern, is not known. Further prospective studies will have to determine whether the presence of these clinical characteristics is predictive of corticosteroid dependency and whether this prediction will be useful for the management of this condition.

Adolescent↗
PubMed1998

[Pseudo-alcoholic hepatitis and cirrhosis caused by amiodarone (Cordarone)].

Amiodarone is an antiarrhythmic drug widely used to treat a variety of supraventricular and ventricular arrhythmias. However its drawback is a very slow elimination and very frequent adverse effects (thyroid, pulmonary, neurologic, ocular, dermatologic, hepatic disorders). We describe a patient who developed a pseudoalcoholic liver disease and a cirrhosis after use of Amiodarone for a long period of time.

Amiodarone↗
PubMed1998

[Clinical case of the month. Hepatoportal sclerosis in a patient treated with azathioprine].

We report a case of hepatoportal sclerosis in a renal transplant patient treated with azathioprine. The initial symptom was ascites. On the biochemical level, there were cholestasis without cytolysis or hepatocellular insufficiency. A presinusoidal portal hypertension was found on haemodynamic studies, without portal thrombosis at CT-scan. A diagnosis of hepatoportal sclerosis was evoked on histology and attributed to azathioprine. This case gives an illustration of a classical albeit rare complication of azathioprine. The indolent pattern of the disease and the risk of variceal bleeding point out the need for a hepatic follow-up during the treatment.

Adult↗
PubMed1997

Association between myelodysplastic syndromes and inflammatory bowel diseases. Report of seven new cases and review of the literature.

We report seven patients with both myelodysplastic syndrome (MDS) and inflammatory bowel disease (IBD): Crohn's disease in six cases, ulcerative colitis in one case. We describe their characteristics, and those of 10 previously published similar cases are presented here. Median age at diagnosis of IBD (61 years) was high, as compared to the usual age at diagnosis of IBD. IBD was diagnosed first in nine cases, MDS first in one patient, and both diseases were diagnosed simultaneously in seven cases. Concerning IBD, there was a strong predominance of Crohn's disease (15/17 cases), with an unusually high frequency of colonic involvement (11/15 cases). MDS, in 12/17 cases, showed no excess of marrow blasts. Cytogenetic analysis was abnormal in five of the 13 evaluable cases. These observations suggest that the association between MDS and IBD may not be fortuitous in some cases, and that, in particular, patients with IBD and anemia of nonobvious origin should be evaluated for MDS. The pathogenesis of those associations, however, remains unclear.

Adult↗
PubMed1997

A high serum concentration of interleukin-6 is predictive of relapse in quiescent Crohn's disease.

BACKGROUND/AIMS: Relapses of Crohn's disease are difficult to predict. We assessed the value of serum level of interleukin-6, tumour necrosis factor alpha (TNF-alpha) and soluble TNF receptors as predictors of relapse in quiescent Crohn's disease. PATIENTS/METHODS: Thirty-six patients with inactive Crohn's disease, treated or not, were included. Various clinical and biological parameters, including interleukin-6, TNF-alpha and soluble TNF receptors serum levels were measured at inclusion in the study and the patients were followed clinically for 1 year. The relapse was defined as a Crohn's Disease Activity Index (CDAI) greater than 150 with an increase greater than 100 compared to the inclusion value. We analysed the ability of these parameters to predict relapse in parallel to clinical characteristics and other laboratory parameters. RESULTS: Among the 32 variables tested, interleukin-6 serum level had the greatest ability to predict the time-to-relapse, with 17-fold chance of relapse over a 1-year period for patients with an interleukin-6 serum level greater than 20 pg/ml than for patients with a lower level (P < 0.001). A high serum level of the soluble TNF receptors p55 and p75 also had significant predictive value, in contrast to TNF-alpha serum levels. An interleukin-6 serum level greater than 20 pg/ml and either an acid alpha-1-glycoprotein level greater than 1.1 g/l or a soluble interleukin-2 receptor serum level greater than 95 pM/l were risk factors selected by a stepwise multivariate analysis. In both models a good prognosis group was defined by the absence of the two risk factors, a bad prognostic group by the presence of the two risk factors and an intermediate in between. With both models, the good prognosis group included 17 patients who experienced no relapse over the 1-year follow-up, whereas all patients (seven with the first model and six with the second) in the bad prognosis group had a relapse during the follow-up. Looking specifically at two homogeneous subgroups including either naturally/5-aminosalicylic acid (5-ASA) quiescent or corticoid quiescent patients, a very good predictive value for interleukin-6 serum concentration was also found. CONCLUSION: Interleukin-6 serum level alone or in association with other biological parameters such as acid alpha-1-glycoprotein or the soluble interleukin-2 receptor serum level may be useful for predicting the course of the disease in patients with quiescent Crohn's disease.

Adolescent↗
PubMed1997

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.

Acquired Immunodeficiency Syndrome↗
PubMed1996

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.

Administration, Oral↗
PubMed1996

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.

Administration, Oral↗