Louali F.E.,Cardiologie Pediatrique |
Azagoh-Kouadio R.,Cardiologie Pediatrique |
Kammache I.,Cardiologie Pediatrique |
Fouilloux V.,Cardiologie Pediatrique |
And 2 more authors.
Pediatric Cardiology | Year: 2013
A right ventricular outflow tract stent was implanted in a 1-month-old (3.5 kg) baby boy with tetralogy of Fallot and worsening cyanosis to relieve infundibular and pulmonary valve stenosis in the setting of well-developed pulmonary artery branches. This management allowed a symmetric and optimal growth of the pulmonary artery branches, with right and left pulmonary arteries measuring 7-mm (z-score, +1.3 SD) and 7.3-mm (z-score, +1.7 SD), respectively, 3 months after stent implantation. No signs of pulmonary overcirculation developed, and complete surgical repair was performed at the age of 6 months. © 2012 Springer Science+Business Media, LLC.
Oudin C.,Hopital de la Timone Enfants |
Simeoni M.-C.,Research Unit EA 3279 |
Sirvent N.,Nice University Hospital Center |
Contet A.,Hopital dEnfants de Brabois |
And 10 more authors.
Blood | Year: 2011
We evaluate the prevalence and risk factors of the metabolic syndrome (MS) in young adults surviving childhood leukemia. During the years 2007 to 2008, assessment of MS was proposed to all adults included in the Leucémie de l'Enfant et de l'Adolescent program, a French prospective multicentric cohort of leukemia survivors. Among 220 eligible patients, 184 (83.6%) had complete evaluation. Median age at evaluation and follow-up duration were 21.2 and 15.4 years. Overall prevalence of MS was 9.2% (95% confidence interval, 5.5-14.4). There was no association of MS with sex, age at diagnosis, leukemia subtype, steroid therapy, and central nervous system irradiation. Patients were stratified according to 4 therapeutic modalities: chemotherapy alone (n = 97), chemotherapy and central nervous system irradiation (n = 27), hematopoietic stem cell transplantation (HSCT) without (n = 17) or with (n = 43) total body irradiation (TBI). MS occurred in 5.2%, 11.1%, 5.9%, and 18.6% of them, respectively. The higher risk observed in the HSCT-TBI group was significant in univariate and in multivariate analysis (odds ratio [OR] = 3.9, P = .03). HSCT with TBI was associated with a higher rate of hypertriglyceridemia (OR = 4.5, P=.004), lowlevel of high-density lipoprotein cholesterol (OR = 2.5, P = .02), and elevated fasting glucose (OR = 6.1, P = .04) So, TBI is a major risk factor for MS. Further studies are warranted to explain this feature. © 2011 by The American Society of Hematology.
Bensman A.,Hopital Trousseau |
Broux F.,Hopital Charles Nicolle |
Cailliez M.,Hopital de la Timone Enfants |
Jacqz-Aigrain E.,French Institute of Health and Medical Research
British Journal of Clinical Pharmacology | Year: 2010
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • MMF has been proposed as a treatment of steroid-dependent nephrotic syndrome and in the recent years, several studies have suggested its positive effect in preventing relapses. WHAT THIS PAPER ADDS • The population pharmacokinetics of MPA was first evaluated in children with idiopathic nephrotic syndrome and data fitted well with a two-compartment model with first-order absorption and lag time. • Body weight and serum albumin had a significant impact on oral clearance. • A three-point (T0, T1 and T4h) Bayesian estimator of AUC0-12 was developed. AIMS: To develop a population pharmacokinetic model for mycophenolic acid (MPA) in children with idiopathic nephrotic syndrome (INS) treated with mycophenolate mofetil (MMF), identify covariates that explain variability and determine the Bayesian estimator of the area under the concentration-time curve over 12 h (AUC0-12). METHODS: The pharmacokinetic model of MMF was described from 23 patients aged 7.4 ± 3.9 years (range 2.9-14.9) using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment model with lag-time and first-order absorption and elimination was developed. The final model was validated using visual predictive check. Bayesian estimator was validated using circular permutation method. RESULTS: The population pharmacokinetic parameters were apparent oral clearance 9.7 l h-1, apparent central volume of distribution 22.3 l, apparent peripheral volume of distribution 250 l, inter-compartment clearance 18.8 l h-1, absorption rate constant 5.16 h-1, lag time 0.215 h. The covariate analysis identified body weight and serum albumin as individual factors influencing the apparent oral clearance. Accurate Bayesian estimation of AUC0-12 was obtained using the combination of three MPA concentrations measured just before (T 0), 1 and 4 h (T1 and T4) after drug intake with a small error of 0.298 μg h-1 ml-1 between estimated and reference AUC0-12. CONCLUSIONS: The population pharmacokinetic model of MPA was developed in children with INS. A three-point (T0, T1 and T4h) Bayesian estimator of AUC 0-12 was developed and might be used to investigate the relation between MPA pharmacokinetic and pharmacodynamics in children with INS and determine if there is any indication to monitor MPA exposure in order to improve patient outcome based on individual AUC-controlled MMF dosing. © 2010 The Authors.
Zhao W.,French Institute of Health and Medical Research |
Fakhoury M.,French Institute of Health and Medical Research |
Brochard K.,Hopital Mere et Enfant |
Niaudet P.,Hopital Necker Enfants Malades |
And 7 more authors.
Journal of Clinical Pharmacology | Year: 2010
The objective was to develop a population pharmacokinetic-pharmacogenetic model of mycophenolic acid following administration of mycophenolate mofetil (MMF) in de novo pediatric renal-transplant patients and identify factors that explain variability. The pharmacokinetic samples were collected from 89 de novo pediatric renal-transplant patients treated with MMF and studied during the first 60 postoperative days. All patients were genotyped for UGT1A8-A9, UGT2B7, and ABCC2. Population pharmacokinetic analysis was performed with the NONMEM and was validated using bootstrap visual predictive check. The pharmacokinetic data were best described by a 2-compartment model with Erlang distribution to describe the absorption phase. The covariate analysis identified body weight as an individual factor influencing central volume of distribution and concomitant immunosuppressive medication and identified body weight and UGT2B7 802C>T genotype as individual factors influencing apparent oral clearance (CL/F) of MMF. CL/F in cyclosporine-MMF-treated patients was 33% higher than in tacrolimus-MMF-treated patients. The CL/F was significantly lower in patients with UGT2B7 802 C/C genotype compared with patients with UGT2B7 802 C/T and 802T/T genotypes, and this effect was independent of concomitant immunosuppressive medication or body weight. The population pharmacokinetic- pharmacogenetic model of mycophenolic acid was validated. Body weight, concomitant medication, and UGT2B7 genotype contribute significantly to the interindividual variability of MMF disposition in pediatric renal-transplant patients. © The Author(s) 2010.
Hazekamp M.G.,Leids Universitair Medisch Centrum |
Gomez A.A.,Leids Universitair Medisch Centrum |
Koolbergen D.R.,Leids Universitair Medisch Centrum |
Hraska V.,Deutsches Kinderherzzentrum |
And 6 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2010
Objectives: Optimal surgical management for patients with transposition of the great arteries (TGA), ventricular septal defect (VSD) and left ventricular outflow obstruction (LVOTO) remains controversial. Although the Rastelli operation has been the most widely performed surgical procedure during the past decades, several studies have shown its suboptimal long-term prognosis. Other operations have been developed to improve results. This study was performed to compare the outcomes of the different surgical approaches for patients with TGA, VSD and LVOTO, as well as to determine risk factors for mortality and re-intervention. Methods: Records from 146 patients undergoing surgery from 1980 to 2008 from eight European hospitals were reviewed. Median age at operation was 21.5 months (range 0.2-165.1 months), and median weight was 10.0 kg (range 2.0-41.0 kg). Surgical procedures involved were the Rastelli procedure (82), arterial (24) and atrial (5) switch operation with relief of LVOTO, Réparation à l'Etage ventriculaire (REV) procedure (7) and the Metras modification (24), as well as the Nikaidoh procedure (4). Results: The overall survival was 88%, 88% and 58% at 1, 10 and 20 years, respectively. The overall event-free survival was 80%, 45% and 26% at 1, 10 and 20 years, respectively. The REV procedure and the Metras modification were found to have the best long-term results in both survival and event-free survival rates. Multivariate analysis revealed year of operation, non-commitment of the VSD and prolonged cardiopulmonary bypass (CPB) time as risk factors for mortality while age at surgery, year of operation and type of corrective surgery were risk factors for re-intervention. Conclusions: Different surgical approaches have been developed for patients with TGA, VSD and LVOTO. The REV procedure and the Metras modification were observed to have favourable long-term results in survival and event-free survival rates. Aortic translocation techniques such as the Nikaidoh procedure seem promising, but further studies will be needed to confirm this in the long term. © 2010 European Association for Cardio-Thoracic Surgery.
PubMed | Service dimagerie pediatrique et prenatale, hopital de la Timone Enfants and Institute Mediterraneen Of La Reproduction Et Fondation
Type: Journal Article | Journal: Diagnostic and interventional imaging | Year: 2016
Aortic coarctation is a local narrowing of the aortic lumen, which is located at the level of the isthmus in 95% of patients. Aortic coarctation accounts for 5 to 8% of all congenital heart diseases. It may have an acute presentation in the form of heart failure in the neonate or may be discovered incidentally in adult because of severe treatment-resistant hypertension. Ultrasound may reveal the presence of aortic coarctation during the antenatal period. In this situation, associated abnormalities should be investigated (including karyotype), because they influence prognosis and indicates whether or not the birth should occur in a center with pediatric cardiology expertise. Postnatally, ultrasound and chest radiography are the basic imaging work-up. Computed tomography is often the second line imaging investigation in infants and young children for whom magnetic resonance imaging fails to confirm the diagnosis. Magnetic resonance imaging with cardiac synchronization is the preferred imaging tool in the post-treatment period. Aortic coarctation may be treated surgically or by endovascular techniques. Potential complications should be searched for using ultrasound and magnetic resonance imaging.
Catanese M.,Rothschild |
Popovici C.,Hopital de la Timone Enfants |
Proust H.,Hopital de la Timone Enfants |
Hoffart L.,Hopital de la Timone Enfants |
And 4 more authors.
Investigative Ophthalmology and Visual Science | Year: 2011
PURPOSE. To assess corneal epithelial cell survival after keratoplasty. METHODS Corneal impression cytology (CIC) was performed on sex-mismatched corneal transplants. Fluorescent in situ hybridization (FISH) with sex chromosome-specific probes was performed to identify epithelial cell mosaicism and therefore allocate the donor or recipient origin of the cells. Twenty-four samples of corneal epithelial cells derived from 21 transplanted patients were analyzed. All patients received post-operative treatment using dexamethasone eye drops, with progressive tapering over 18 months, and nine patients also received 2% cyclosporine eye drops. RESULTS. Out of the 24 samples reaching quality criteria, sex mosaicism was found in 13, demonstrating the presence of donor-derived cells at the center of the graft for at least 211 days post keratoplasty. Kaplan-Meier analysis established a median survival of donor corneal epithelial cells of 385 days. Although not statistically significant, the disappearance of donor cells seemed to be delayed and the average number of persistent cells appeared to be greater when 2% cyclosporine was used topically as an additional immunosuppressive therapy. CONCLUSIONS. The combination of corneal impressions and FISH analysis is a valuable tool with negligible side effects to investigate the presence of epithelial cell mosaicism in sex-mismatched donor transplants. Epithelial cells survived at the center of the graft with a median survival of more than one year, suggesting slower epithelial turnover than previously described. © 2011 The Association for Research in Vision and Ophthalmology, Inc.
PubMed | Hopital de la Timone Enfants
Type: Journal Article | Journal: Acta haematologica | Year: 2012
This study investigated immune recovery and the effect of cytomegalovirus (CMV) infection on the early stages of T-lymphocyte recovery after cord-blood transplantation (CBT) from unrelated donors to 24 children. In addition, 15 children who were recipients of a bone-marrow transplant (BMT) were studied concomitantly. The main objectives of the study were whether lymphocytes from CBT recipients were capable of rapid qualitative differentiation in the effector memory (EM) stage, of regenerating de novo nave cells and of responding to CMV infection. Results showed that CB lymphocytes were mainly differentiated into the EM stage at 3 months and into the nave stage at 6 months. CMV infection induced a dramatic increase in CD8 but not CD4 T-cell counts, and differentiation into the EM stage with high perforin contents. Our data suggest that CB lymphocytes are capable of rapid differentiation in children, but stabilization of lymphocyte counts in children is associated with effective nave subset regeneration at 6 months. Moreover, the T-cell repertoire is capable of rapid adjustment when CMV infection occurs.
PubMed | University Of Medicine Et Pharmacie Iuliu Hatieganu and hopital de La Timone Enfants
Type: Journal Article | Journal: Diagnostic and interventional imaging | Year: 2016
To evaluate the use of non-ECG-gated computed tomography (CT) angiography to describe pulmonary and coronary defects in patients with tetralogy of Fallot (TOF).This retrospective study was carried out on TOF patients having undergone pre-operative non-ECG-gated CT angiography between February 2007 and September 2012. The following clinical parameters were recorded: mean age at CT angiography, sex, the existence of genetic disease and the need to sedate the patient prior to CT angiography. CT data were analyzed retrospectively to determine the site(s) of pulmonary stenosis (infundibular, valvular or arterial), the size of pulmonary arteries and the presence of anomalous coronary artery courses. CT findings were then compared to the anatomy observed during surgery.Thirty-five patients were included in the study. The mean age was 4.301.91months (boys/girls=17/18). Two patients had associated chromosome disorders (one 22q11 microdeletion and one CHARGE syndrome). Sixteen patients (45.71%) were sedated prior to CT. Pulmonary artery assessment revealed 24 patients (68.57%) with infundibular stenosis, 5 (17.5%) with infundibular and/or valvular stenosis, and 6 (21%) with anomalous pulmonary arteries. CT angiography also evidenced anomalous coronary arteries in 8 patients (22.85%).Due to its reduced scanning time and high spatial resolution, non-ECG-gated CT angiography is a non-invasive imaging modality that provides accurate information on pulmonary and coronary artery anatomy in patients with TOF.
PubMed | Hopital de la Timone Enfants
Type: Journal Article | Journal: Blood | Year: 2011
We evaluate the prevalence and risk factors of the metabolic syndrome (MS) in young adults surviving childhood leukemia. During the years 2007 to 2008, assessment of MS was proposed to all adults included in the Leucmie de lEnfant et de lAdolescent program, a French prospective multicentric cohort of leukemia survivors. Among 220 eligible patients, 184 (83.6%) had complete evaluation. Median age at evaluation and follow-up duration were 21.2 and 15.4 years. Overall prevalence of MS was 9.2% (95% confidence interval, 5.5-14.4). There was no association of MS with sex, age at diagnosis, leukemia subtype, steroid therapy, and central nervous system irradiation. Patients were stratified according to 4 therapeutic modalities: chemotherapy alone (n = 97), chemotherapy and central nervous system irradiation (n = 27), hematopoietic stem cell transplantation (HSCT) without (n = 17) or with (n = 43) total body irradiation (TBI). MS occurred in 5.2%, 11.1%, 5.9%, and 18.6% of them, respectively. The higher risk observed in the HSCT-TBI group was significant in univariate and in multivariate analysis (odds ratio [OR] = 3.9, P = .03). HSCT with TBI was associated with a higher rate of hypertriglyceridemia (OR = 4.5, P = .004), low level of high-density lipoprotein cholesterol (OR = 2.5, P = .02), and elevated fasting glucose (OR = 6.1, P = .04) So, TBI is a major risk factor for MS. Further studies are warranted to explain this feature.