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Biomedical subjects

O Goulet

Publications and source records attributed to O Goulet.

At least 19 recordsLinked to original sources
PubMed2006

Microbial induction of CARD15 expression in intestinal epithelial cells via toll-like receptor 5 triggers an antibacterial response loop.

With the discovery of CARD15 as susceptibility gene for Crohn's disease (CD) a first link to a potential defect in the innate immune system was made. In this work we aimed to analyze enterocyte NOD2/CARD15 expression and regulation in response to bacterial motifs and the consequences of the most common CD-specific CARD15 mutation on antibacterial responses of normal intestinal epithelial cells (IEC). Under normal conditions, IEC lines and ileal enterocytes did not express NOD2/CARD15 mRNA or protein, contrary to IEC derived from inflammatory CD sections. In vitro analyses revealed that the simple contact with non-pathogenic commensal E. Coli K12 was sufficient to induced NOD2/CARD15 mRNA and protein in human IEC (HIEC). We identified bacterial flagellin interacting with TLR5 as major motif in this regulation of NOD2/CARD15. E. Coli mutants not expressing flagellin (DeltaFliC) failed to induce CARD15. Similarly, in HIEC transfected with a plasmid encoding dominant negative TLR5, no CARD15 induction was observed after K12 contact. Isolated TLR2 or TLR4 stimulation had no or only a marginal effect on NOD2/CARD15 expression. NOD2/CARD15 negative HIEC were unresponsive to muramyl dipeptide (MDP), but once NOD2/CARD15 was induced, HIEC and Caco2 cells responded to intra or extracellular MDP presentation with the activation of the NFkB pathway. IEC transfected with the Crohn-specific CARD15 mutant (F3020insC, FS) failed to activate NFkB after MDP-challenge, in contrast to CARD15WT IEC. In response to MDP, IEC induced a massive antibacterial peptide (ABP) response, seen in the apical release of CCL20. This was completely abolished in IEC carrying CARD15FS. These data suggest a critical role of NOD2/CARD15 in the bacterial clearance of the intestinal epithelium while CD-specific mutated NOD2/CARD15 causes an impaired epithelial barrier.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2006

Efficacy of methotrexate in pediatric Crohn's disease: a French multicenter study.

BACKGROUND: Immunosuppressors play a major role in maintaining remission in Crohn's disease (CD). In patients who do not tolerate or escape therapy with azathioprine (AZA)/6-mercaptopurine, there is a marked need for other immunosuppressive drugs. The aim of the present study was to evaluate the efficacy and safety of methotrexate (MTX) in children with active CD. METHODS: In a retrospective multicenter (n = 3) study, the efficacy of MTX to induce complete remission or a clinical improvement was analyzed in 61 children with active CD. RESULTS: CD was diagnosed at a mean age of 11.1 +/- 2.3 years, and MTX was introduced 3.1 +/- 2.2 years after diagnosis. Indications to use MTX were a nonresponse to or relapse under AZA (n = 42) or AZA intolerance/toxicity (n = 19). MTX improved or induced complete remission in 49 patients (80%), of whom 18 (29.5%) relapsed after 13 +/- 10 months of treatment. Under MTX medication, complete remission was observed in 39%, 49%, and 45% at 3, 6, and 12 months, respectively. Follow-up over at least 24 months in 11 children confirmed a sustained remission on MTX monotherapy up to 40 months. Adverse reactions were observed in 14 patients (24%), requiring discontinuation of MTX in 6 children (10%) (liver enzyme elevation, n = 2; varicella-zoster, n = 1; nausea, n = 3). MTX allowed corticosteroid discontinuation in 36 patients. CONCLUSIONS: MTX improved the clinical course in most pediatric CD patients who escaped or did not tolerate AZA. Short-time toxicity of MTX resulted in drug discontinuation in <10%. These data point to a beneficial and safe use of MTX in the treatment of pediatric CD.

Azathioprine↗
PubMed2006

Severe dysimmune cytopenia in children treated with tacrolimus after organ transplantation.

Rare cases of dysimmune phenomena after solid organ transplantation were described in the past. In the present series, we describe six children who developed severe dysimmune anemia or thrombocytopenia while treated with tacrolimus after liver or small bowel transplantation. All patients were off steroids or under low doses alternate day steroid medication when dysimmune cytopenia developed. All patients had positive anti-platelets antibodies and/or Coombs' positive anemia. Therapy was successful in all six patients with a rapid response to corticosteroids in three children, and to anti-CD20 monoclonal antibodies (rituximab) in the three others. The pathogenesis of these rare dysimmune/autoimmune disorders might be related to the interference of tacrolimus with T-cell functions and/or the endogenous control mechanisms of T-lymphocyte activation and down-regulation. Although rare, these complications must be known when discussing protocols of immunosuppression.

Anemia↗
PubMed2005

Outcome and long-term growth after extensive small bowel resection in the neonatal period: a survey of 87 children.

UNLABELLED: This retrospective study aims to analyze the outcome, the prognosis factors and the long-term growth of children after extensive small bowel (SB) resection in the neonatal period. PATIENTS AND METHODS: 87 children, born between 1975 and 1991 who had undergone extensive neonatal small bowel resection, were followed up over a mean period of 15 years. Anatomical data influencing PN dependency and duration were analyzed. Data on height and weight were collected and compared using growth standards. Final heights were studied for patients who achieved their puberty and compared to predicted height based on Tanner's formula. Patients were analyzed according to PN weaning and growth: children still receiving PN (group A), patients weaned from initial PN but requiring PN once again or enteral feeding (group B), and children with permanent intestinal autonomy (group C). RESULTS: The overall survival is 89.7 %, depending on the date of birth. The duration of PN-dependency varies according to the intestinal length and the presence of the ileocaecal valve (ICV). All patients who remain PN dependent had less than 40 cm of small bowel and/or the absence of ICV. Patients in group B had a mean small bowel length of 35 +/- 19 cm, resection of the ICV in 50 % of cases, and a PN duration of 47.4 +/- 23.8 months. There was a significant decrease in height and weight gain within the 4 years after cessation of PN, requiring enteral or parenteral feeding. Patients in group C had a mean small bowel length of 57 +/- 19 cm, presence of ICV in 81 % of cases and a PN duration of 16.1 +/- 11.4 months. After PN weaning, they grow up normally with normal puberty and final height as predicted from genetic target height. CONCLUSION: PN duration is influenced by the length of residual SB and the absence of ICV. With good anatomic prognosis factors and short duration of initial PN, normal long-term growth may be predicted. Conversely, poor anatomical factors and protracted initial PN require careful monitoring of growth and may sometimes require nutritional support to be restarted. The last group, permanently dependent on PN, might be candidates for intestinal transplantation.

Body Size↗
PubMed2005

Fecal tumor necrosis factor-alpha and calprotectin as differential diagnostic markers for severe diarrhea of small infants.

OBJECTIVE: The etiology of early-onset diarrhea of neonates and small infants that persists despite bowel rest is heterogeneous. Two different categories of disorders presenting with diarrhea in the first weeks of life can be distinguished: constitutive intestinal epithelial disorders (microvillus atrophy [MVA] or epithelial dysplasia [ED]) and immune-inflammatory disorders, (autoimmune enteropathy [AIE] or inflammatory colitis [IC]). We aimed to evaluate in a prospective manner the use of fecal inflammatory markers in the differential diagnosis of severe persistent diarrhea. MATERIAL AND PATIENTS: Twenty-five patients (17 males) were enrolled in this study (median age 8 months). Fourteen children had a constitutive enterocyte disorder (group 1: MVA = 8, ED = 6), and 11 patients had an immuno-inflammatory disease (group 2: AIE = 5, IC = 6). Stool samples were collected at the time of diagnosis and stored at -80 degrees until tumor necrosis factor (TNF)-alpha and calprotectin were measured by enzyme-linked immunoadsorbent assay. RESULTS: No significant differences in age at onset of diarrhea or in stool volumes were observed between both groups. In group 1, fecal TNF-alpha was undetectable/normal in 14 of 14 children, whereas group 2 showed dramatically elevated TNF-alpha levels (mean 3,104, range 237-18,078 pg/g) in 8 of 11 patients. Similarly, calprotectin levels were undetectable/normal in 14 of 14 patients in group 1 and highly raised in 11 of 11 patients in group 2 (median 1,145, range 375-3,095 mug/g), P < 0.01. Under therapy, these inflammatory parameters normalized. CONCLUSIONS: Determination of fecal inflammatory markers is a simple method helping to distinguish constitutive from immuno-inflammatory etiologies of severe persistent diarrhea. These data also suggest that constitutive enterocyte disorders are not accompanied by an inflammatory mucosal reaction.

Age of Onset↗
PubMed2004

[Peritoneal tuberculosis in children: report of two cases].

UNLABELLED: Peritoneal tuberculosis is an uncommon presentation of extra-pulmonary tuberculosis in children. It usually presents as ascites, abdominal pain, anorexia and weight loss. CASES REPORT: We report two adolescent patients who presented with ascites, fever, weight loss and abdominal distension. In one case, the diagnosis was late, and confirmed by ascites culture. In the second case, a laparoscopy was performed and showed whitish nodules involving the entire abdominal cavity, compatible with peritoneal tuberculosis, later confirmed bacteriologically. CONCLUSION: Peritoneal tuberculosis presents with nonspecific symptoms. Because laboratory investigations may not be helpful, diagnosis may be difficult. Peritoneal-fluid adenosine deaminase (ADA) determination and coelioscopy seem to be the best way to make a rapid diagnosis.

Abdominal Pain↗
PubMed2004

Effects of long-term consumption of a fermented infant formula (with Bifidobacterium breve c50 and Streptococcus thermophilus 065) on acute diarrhea in healthy infants.

OBJECTIVE: To determine whether long-term consumption of a fermented infant formula could influence the incidence of acute diarrhea and its severity in healthy infants. METHOD: Nine hundred seventy-one infants, ranging in age from 4 to 6 months, were included in a randomized, double-blind, placebo-controlled trial during a period of 5 months. They consumed daily either a fermented infant formula (FF) (fermentation with Bifidobacterium breve C50 and Streptococcus thermophilus 065) or a standard infant formula (SF) of the same nutritional composition. EVALUATION CRITERIA: Number and duration of acute diarrhea episodes were evaluated. Severity of the episodes was determined by the number of hospital admissions, incidence of dehydration, number of medical consultations, number of oral rehydration solution prescriptions, and number of formula switches. RESULTS: Growth of the infants and acceptability of the formulas were identical in the two groups. Incidence, duration of diarrhea episodes, and number of hospital admissions did not differ significantly between groups. Episodes were less severe in the FF (fermented formula) group. There were fewer cases of dehydration 2.5%versus 6.1% (P = 0.01), fewer medical consultations (46%v 56.6%, P = 0.003), fewer ORS prescriptions 41.9%v 51.9% (P = 0.003) and fewer switches to other formulas (59.5%v 74.9%, P = 0.0001) in FF infants compared to SF. CONCLUSION: A fermented formula may reduce the severity of acute diarrhea among healthy young infants. This outcome may be linked to the bifidogenic effects of fermentation products and their interactions with the intestinal immune system.

Acute Disease↗
PubMed2004

Induction of T lymphocyte apoptosis by sulphasalazine in patients with Crohn's disease.

BACKGROUND: Lamina propria T lymphocytes (LPL) of the intestinal mucosa are chronically activated in Crohn's disease (CD). Defective apoptosis of activated LPL was proposed as a key pathogenic mechanism. In fact, increased expression of antiapoptotic molecules was observed in CD LPL. In the present work, we aimed to analyse the effects and underlying molecular mechanisms of 5-amino salicylic acid (5-ASA) and derivatives on apoptosis of LPL and peripheral blood lymphocytes (PBL) in patients with CD compared with ulcerative colitis (UC) and in non-inflammatory controls. METHODS: PBL and LPL were isolated by Ficoll-Hypopaque gradient centrifugation and the EGTA-collagenase method, respectively. PBL/LPL were stimulated with FasL, 5-ASA, sulphapyridine, and sulphasalazine for 24/48 hours and apoptosis was quantified by flow cytometry (annexin V- propidium iodide method) and immunofluorescence. The molecular mechanisms of drug induced apoptosis were analysed in wild-type and FADD-/- Jurkat T cells using western blots and caspase assays. RESULTS: While PBL displayed a normal apoptosis pattern after Fas stimulation in patients with active CD, LPL from inflammatory areas were highly resistant. Comparable resistance to apoptosis was observed in LPL of UC patients. In contrast with 5-ASA, which did not induce apoptosis in lymphocytes, sulphasalazine proved to be a potent proapoptotic agent. Sulphasalazine induced T lymphocyte apoptosis was independent of the Fas pathway but associated with marked downregulation of antiapoptotic bcl-xl and bcl2, activation of the mitochondrial apoptosis signalling pathway, and subsequent activation of caspase-9 and caspase-3. CONCLUSION: The beneficial effect of sulphasalazine in treating inflammatory bowel disease is at least in part attributable to its proapoptotic effects on LPL which allows potent downregulation of lymphocyte activation.

Adolescent↗
PubMed2003

[Feeding of infants based on age. Practice guidelines].

This paper presents practical guidelines for nutrition and feeding of infants and toddlers including vitamin D, vitamin K and fluoride supplementations and preventive measures at risk for food allergy based on family history.

Breast Feeding↗
PubMed2002

[Study of psychological repercussions of 2 modes of treatment of adolescents with Crohn's disease].

UNLABELLED: No study has yet compared the respective psychological impact of corticotherapy and enteral nutrition in the treatment of Crohn's disease, and especially, the psychological problems linked to the wearing of a nasogastric tube 24 hours a day. The goal of this study was to collect comparative information regarding the real-life experience and the feeling of these two treatments. PATIENTS AND METHODS: From September 1997 to February 1998 at the clinic of inflammatory bowel diseases of the hospital Necker-Enfants malades, 51 patients aged 12 to 18 (average 15) participated in this study. Thirty [15 on corticotherapy (CT); 15 on enteral nutrition (EN)] answered a questionnaire inspired by a similar Canadian questionnaire (Inflammatory Bowel Disease Questionnaire), and 21 passed Spielberger's anxiety tests, Beck's depression tests and a psychological interview. RESULTS TREATMENT: According to the 30 questionnaires the appreciation of the therapeutic results was similar in the two treatments, the majority of patients respected their treatment (only one patient on EN ate secretly and two on CT stopped their corticotherapy). Of the 15 EN questionnaires: nine out of 15 patients responded well to the suspension of oral feeding, two were hungry, nine experienced cravings and ten avoided meals during their treatment. From a cosmetic point of view, six/14 (43%) found it difficult putting up with the nasogastric tube 24 hours a day, and eight/15 (53%) on CT found the facial swelling difficult to bear. According to the 21 psychological interviews, eight patients deemed EN efficient, while only four felt the same about CT. Of the 11 EN psychological interview, no adolescent patients were hungry, eight had cravings and nine avoided meals during their treatment, seven mentioned they felt different and seven described how EN had upset the family's routine. Nine (82%) talked about how difficult it was to put up with the nasogastric tube 24 hours a day from a cosmetic standpoint while eight/ten (80%) on CT found the facial swelling difficult to live with. Seven complained that they had been the victims of verbal abuse. Quality of life: According to the 30 questionnaires, eight/15 patients on EN missed an average of 15 days of school against five/15 patients on CT, ten patients judged that EN restricted their daily lives and nine mentioned the daily difficulties to wear a tube 24 hours a day. TESTS: Spielberger's test of anxiety revealed that on average, the 11 patients on EN who were interviewed suffered the first level of anxiety, while the ten patients on CT felt the second level. As for the Beck's depression test, the 11 patients on NE suffered the first level of depression on average, while those on CT were subject to the second level. CONCLUSION: This study demonstrated that EN was perceived as being more disruptive to patients daily lives than CT and defines the difficulties linked to the suspension of oral feeding and the wearing of a naso-gastric tube. The study also describes the difficulties involved in coping with the side effects of CT, one example being facial swelling which can be as unpleasant from a cosmetic point of view as wearing of a naso-gastric tube.

Adolescent↗