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1.
Aliment Pharmacol Ther ; 39(8): 823-33, 2014 Apr.
Article de Anglais | MEDLINE | ID: mdl-24612000

RÉSUMÉ

BACKGROUND: Diagnosis of inflammatory bowel disease (IBD) is based on clinical presentation, colonoscopy and histology. Differentiation of Crohn's disease (CD) and ulcerative colitis (UC) can be difficult in some patients. Endoscopic ultrasound (EUS) provides high resolution images of the gastrointestinal wall (GI) and may be an alternative to differentiate CD/UC. AIM: EUS of the GI layers in patients with IBD and healthy controls (HC) for the differential diagnosis of UC/CD in a prospective, blinded study. METHODS: Consecutive patients with CD, UC or HC underwent EUS in the mid sigmoid colon with a forward-viewing radial echoendoscope. Mucosal, submucosal, total wall thickness (TWT) and locoregional lymphnodes (LN) were assessed by EUS in a blinded fashion. TWT was correlated with macroscopic IBD scores and histological inflammation scores. RESULTS: Total wall thickness of 61 HC was 1.71 ± 0.02 mm, and 3.51 ± 0.15 mm in n = 52 with active IBD. In patients with active UC significant thickening of the mucosa was observed but nearly normal submucosa and m.propria. In active CD significant thickening of the submucosal layer was seen with nearly normal mucosa and m.propria [MucosaUC  = 2.08 ± 0.11 mm, MucosaCD  = 1.32 ± 0.17 mm (P = 0.0001); SubmucosaUC  = 1.01 ± 0.08 mm, SubmucosaCD  = 2.01 ± 0.22 mm (P = 0.0001)]. In 73.7% of patients with active CD, but in none with UC, paracolonic lymph nodes were detected. When mucosal-submucosal and TWT and LNs were combined, the sensitivity was 92.3% for the differentiation of active UC/CD. There was a strong correlation of TWT with histological inflammation scores (UC: r = 0.43; CD: r = 0.69). CONCLUSIONS: Increased total wall thickness has a high positive predictive value for active IBD. EUS can differentiate active UC from CD and quantify the level of colonic inflammation.


Sujet(s)
Rectocolite hémorragique/diagnostic , Coloscopie/méthodes , Maladie de Crohn/diagnostic , Endosonographie/méthodes , Adulte , Sujet âgé , Études cas-témoins , Rectocolite hémorragique/anatomopathologie , Maladie de Crohn/anatomopathologie , Diagnostic différentiel , Femelle , Humains , Mâle , Adulte d'âge moyen , Études prospectives , Méthode en simple aveugle
2.
Clin Pharmacol Ther ; 84(1): 43-6, 2008 Jul.
Article de Anglais | MEDLINE | ID: mdl-18322448

RÉSUMÉ

Budesonide treatment of chronic inflammatory bowel disease commonly leads to non-response or adverse reactions, possibly because of alterations in efflux transport mediated by the ABCB1 gene product P-glycoprotein or metabolism by CYP3A isoenzymes. Two groups, each consisting of nine healthy volunteers, one with the CYP3A5(*)1/(*)3 genotype (expressors) and the other with the CYP3A5(*)3/(*)3 genotype (non-expressors), were given a single oral dose of 9 mg budesonide. Plasma and urine concentrations of budesonide and its major metabolites were determined using liquid chromatography-tandem mass spectrometry. Subsequently, rectosigmoidal biopsies were taken for analysis of messenger RNA (mRNA) expression. Budesonide pharmacokinetics did not differ between genotype groups. However, intestinal CYP3A4 expression was shown to correlate directly with partial metabolic clearances of 16-hydroxy-prednisolone (r(2) = 0.30; P = 0.010) and 6-hydroxy-budesonide (r(2) = 0.25; P = 0.016), but inversely with budesonide AUC(0-24 h) (r(2) = 0.18; P = 0.040). Interestingly, a strong correlation was found between CYP3A5 and ABCB1 expression in CYP3A5 expressors (r(2) = 0.79; P = 0.001). This study suggests that intestinal CYP3A4 expression has an impact on budesonide pharmacokinetics. Moreover, CYP3A5 and ABCB1 expression appears to be coregulated.


Sujet(s)
Glycoprotéine P/génétique , Budésonide/pharmacocinétique , Cytochrome P-450 CYP3A/génétique , Régulation de l'expression des gènes codant pour des enzymes/physiologie , Muqueuse intestinale/métabolisme , Sous-famille B de transporteurs à cassette liant l'ATP , Glycoprotéine P/biosynthèse , Administration par voie orale , Adulte , Budésonide/administration et posologie , Budésonide/sang , Cytochrome P-450 CYP3A/biosynthèse , Femelle , Régulation de l'expression des gènes codant pour des enzymes/effets des médicaments et des substances chimiques , Génotype , Humains , Absorption intestinale/effets des médicaments et des substances chimiques , Absorption intestinale/physiologie , Muqueuse intestinale/effets des médicaments et des substances chimiques , Mâle
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