Van Der Feen D.E.,University of Groningen |
Dickinson M.G.,University of Groningen |
Bartelds B.,University of Groningen |
Borgdorff M.A.J.,University of Groningen |
And 4 more authors.
Journal of Heart and Lung Transplantation | Year: 2016
Background Pulmonary arterial hypertension (PAH) is hallmarked by the development of neointimal lesions. The transcription factor Egr-1 seems to play a critical role in neointimal formation in experimental PAH and was identified as a putative target for intervention. In this study we investigated whether Egr-1 is also associated with neointimal-type vascular remodeling in different forms of human PAH or pulmonary hypertension. Methods Using immunohistochemistry, we studied Egr-1 expression specifically in a wide morphologic spectrum of pulmonary arteries in the lung tissue of 72 patients with different forms and stages of PAH, specifically idiopathic PAH (n = 18), advanced-stage congenital heart disease-associated PAH (PAH-CHD) (n = 21), early-stage PAH-CHD (n = 19) and non-neointimal hypoxic pulmonary hypertension (PH) (n = 4), and controls (n = 10). Results In PAH patients, pulmonary vascular expression of Egr-1 protein was abundant, whereas it was sporadic in non-neointimal (hypoxic) PH patients and controls. In PAH-CHD, protein expression was more pronounced in patients with advanced vascular lesions compared to those with less advanced lesions, such as medial hypertrophy. Conclusions Pulmonary vascular Egr-1 expression is significantly increased in patients with PAH, appears specifically associated with neointimal-type vascular remodeling, and correlates with disease progression. These data translate the critical role of Egr-1 in the development of experimental PAH to human pulmonary vascular disease forms. © 2016 International Society for Heart and Lung Transplantation.
Kachaner J.,Service de cardiologie pediatrique
Archives de Pediatrie | Year: 2010
Every medical decision-making is to do justice to the one who suffers and who considers his pain as nonsensical. This requirement falls into 3 universal ethical principles, governing the patient-doctor relationship: the autonomy of the person even if it is a young child, beneficence and non-maleficence. Adhering to these principles gives medical decision-making its ethical dimension. It implies that the doctor makes the best use of the emotions that he feels in front of his patient and/or in front of his relatives: respect for autonomy, the beneficent compassion and the fear of maleficence in diagnosis and care. If a paediatrician combines these 3 affects harmoniously, his attitude is in keeping with the requirement of justice, which is the quintessence of Ethics. However, reality is often more complex, a source of conflicting emotions and, in fine, a source of an anguish whose benefit is yet to alert on the necessity to carry on looking for the right decision-making: the emotional revision consists of a meta-analysis of the objective and subjective data of the problem. It preciously helps to establish a compromise of justice. Eventually, in order to be just, the doctor must include the concern of equity amongst the criteria of his decision-making, in other words a fair allocation of the goods and of the care services. Unfortunately, this concern is undermined by geopolitical, socio-economic and cultural factors, which vary greatly according to the environmental conditions that might mar what should be optimal ethical decisionmaking. The doctor cannot solve these problems on his own, but he has to know them in order to deal with them. © 2010 Elsevier Masson SAS. All rights reserved.
PubMed | Weierstrass Institute for Applied Analysis And Stochastics, Service de Cardiologie Pediatrique, CNRS Fluid Dynamics Institute of Toulouse and French Institute for Research in Computer Science and Automation
Type: Journal Article | Journal: Cardiovascular engineering and technology | Year: 2015
Tetralogy of Fallot is a congenital heart disease characterized over time, after the initial repair, by the absence of a functioning pulmonary valve, which causes regurgitation, and by progressive enlargement of the right ventricle outflow tract (RVOT). Due to this pathological anatomy, available transcatheter valves are usually too small to be deployed there. To avoid surgical valve replacement, an alternative consists in implanting a reducer prior to or in combination with the valve. It has been shown in animal experiments to be promising, but with some limitations. The effect of a percutaneous pulmonary valve reducer on hemodynamics in enlarged RVOT is thus studied by computational modeling. To this aim, blood flow in the RVOT is modeled with CFD coupled to a simplified valve model and 0D downstream models. Simulations are performed in an image-based geometry and boundary conditions tuned to reproduce the pathological flow without the device. Different device designs are built and compared with the initial device-free state, or with the reducer alone. Results suggest that pressure loss is higher for the reducer alone than for the full device, and that the latter successfully restores hemodynamics to a healthy state and induces a more symmetric flow in the pulmonary arteries. Moreover, pressure forces on the reducer and on the valve have the same magnitudes. Migration would occur towards the right ventricle rather than the pulmonary arteries. Results support the thesis that the reducer does not introduce clinically significant pressure gradients, as was found in animal experiments. Such study could help transfer to patients.
PubMed | Center for Pediatric Genomic Medicine, University of Paris Pantheon Sorbonne, French Atomic Energy Commission, Service de Cardiologie Pediatrique and 5 more.
Type: Journal Article | Journal: Nature genetics | Year: 2015
Heterotaxy results from a failure to establish normal left-right asymmetry early in embryonic development. By whole-exome sequencing, whole-genome sequencing and high-throughput cohort resequencing, we identified recessive mutations in MMP21 (encoding matrix metallopeptidase 21) in nine index cases with heterotaxy. In addition, Mmp21-mutant mice and mmp21-morphant zebrafish displayed heterotaxy and abnormal cardiac looping, respectively, suggesting a new role for extracellular matrix remodeling in the establishment of laterality in vertebrates.
PubMed | University of Groningen and Service de Cardiologie Pediatrique
Type: Journal Article | Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation | Year: 2016
Pulmonary arterial hypertension (PAH) is hallmarked by the development of neointimal lesions. The transcription factor Egr-1 seems to play a critical role in neointimal formation in experimental PAH and was identified as a putative target for intervention. In this study we investigated whether Egr-1 is also associated with neointimal-type vascular remodeling in different forms of human PAH or pulmonary hypertension.Using immunohistochemistry, we studied Egr-1 expression specifically in a wide morphologic spectrum of pulmonary arteries in the lung tissue of 72 patients with different forms and stages of PAH, specifically idiopathic PAH (n = 18), advanced-stage congenital heart diseaseassociated PAH (PAH-CHD) (n = 21), early-stage PAH-CHD (n = 19) and non-neointimal hypoxic pulmonary hypertension (PH) (n = 4), and controls (n = 10).In PAH patients, pulmonary vascular expression of Egr-1 protein was abundant, whereas it was sporadic in non-neointimal (hypoxic) PH patients and controls. In PAH-CHD, protein expression was more pronounced in patients with advanced vascular lesions compared to those with less advanced lesions, such as medial hypertrophy.Pulmonary vascular Egr-1 expression is significantly increased in patients with PAH, appears specifically associated with neointimal-type vascular remodeling, and correlates with disease progression. These data translate the critical role of Egr-1 in the development of experimental PAH to human pulmonary vascular disease forms.
PubMed | Center Intercommunal Poissy St Germain en Laye, Clinique Pasteur, Service de Cardiologie Pediatrique, Pediatrie Cardiologie and 11 more.
Type: Journal Article | Journal: European journal of human genetics : EJHG | Year: 2016
The etiology of congenital heart defect (CHD) combines environmental and genetic factors. So far, there were studies reporting on the screening of a single gene on unselected CHD or on familial cases selected for specific CHD types. Our goal was to systematically screen a proband of familial cases of CHD on a set of genetic tests to evaluate the prevalence of disease-causing variant identification. A systematic screening of GATA4, NKX2-5, ZIC3 and Multiplex ligation-dependent probe amplification (MLPA) P311 Kit was setup on the proband of 154 families with at least two cases of non-syndromic CHD. Additionally, ELN screening was performed on families with supravalvular arterial stenosis. Twenty-two variants were found, but segregation analysis confirmed unambiguously the causality of 16 variants: GATA4 (1 ), NKX2-5 (6 ), ZIC3 (3 ), MLPA (2 ) and ELN (4 ). Therefore, this approach was able to identify the causal variant in 10.4% of familial CHD cases. This study demonstrated the existence of a de novo variant even in familial CHD cases and the impact of CHD variants on adult cardiac condition even in the absence of CHD. This study showed that the systematic screening of genetic factors is useful in familial CHD cases with up to 10.4% elucidated cases. When successful, it drastically improved genetic counseling by discovering unaffected variant carriers who are at risk of transmitting their variant and are also exposed to develop cardiac complications during adulthood thus prompting long-term cardiac follow-up. This study provides an important baseline at dawning of the next-generation sequencing era.
Butin M.,Service de Nephrologie |
Mekki Y.,Laboratoire Of Virologie Est |
Phan A.,Service de Nephrologie |
Billaud G.,Laboratoire Of Virologie Est |
And 4 more authors.
Pediatric Infectious Disease Journal | Year: 2013
We report a case of an immunocompetent child who developed parvovirus B19 infection complicated by autoinflammatory disease with myocarditis, tamponade and macrophage activation syndrome. He recovered with immunotherapy including prednisone, immunoglobulins, cyclosporin and anakinra (anti-interleukin-1). The report shows that parvovirus can provoke severe systemic inflammation with acute heart injury and that anti-interleukin-1 might be considered in such parvovirus-related inflammation. Copyright © 2013 Lippincott Williams & Wilkins.
Latour C.,Service de pediatrie |
Veyrier M.,Service de cardiologie pediatrique |
Teyssier G.,Service de pediatrie
Archives de Pediatrie | Year: 2011
We report 2 cases of children who developed a complete atrioventricular block following an infection, varicella without complication initially in the first case and Mycoplasma pneumoniae pneumopathy in the second case, in which a first-degree congenital heart block was diagnosed on this occasion. In case 1, the treatment consisted in oral corticosteroids leading to the recovery of sinus rhythm; the course was unfavorable in the second case and required a permanent pacemaker. This cardiac complication of bacterial or viral infection is rare in children but evolves to permanent conduction disturbance in 1/3 of the cases. It is important to detect this disorder, which is feasible simply by a clinical examination and an electrocardiogram. © 2011 Elsevier Masson SAS.
Van Aerschot I.,Service de cardiologie pediatrique |
Boudjemline Y.,Service de cardiologie pediatrique
Archives de Pediatrie | Year: 2012
With the technological progress, the role of the cardiac catheterization has dramatically changed, moving from diagnostic to therapeutic and becoming adjuvant to surgical procedures. In various congenital heart defects, it allows to postpone the need for surgery or even cancel the surgical indication being less invasive and as powerful as surgery. It is thanks to many technological advances, in particular with the development of devices with memory alloy, that the catheterization makes such great strides today, and the miniaturization of the prosthetic material makes it possible to push back more and more the limits of feasibility which remain related to the smallness of the vascular accesses at the newborn age. The future of this discipline lies in the hybrid procedures, where a true teamwork between the surgeons and the pediatric cardiologists makes it possible to bring the best therapeutic strategy for patients with congenital heart defects. © 2011.
PubMed | Service de cardiologie pediatrique
Type: | Journal: Archives de pediatrie : organe officiel de la Societe francaise de pediatrie | Year: 2017
A patent ductus arteriosus, very common in the preterm infant (incidence up to 70% in infants less than 28 weeks gestational age), causes a left-to-right shunt leading to overload of the pulmonary circulation and low systemic blood flow. These hemodynamic anomalies are associated with a higher incidence of respiratory, neurological, and digestive complications of prematurity, as well as a higher mortality rate. Although growing knowledge about the natural history, the pathophysiology, and the mechanisms of closure of the ductus arteriosus has resulted in therapeutic progress, management of the patent ductus arteriosus in the preterm infant is still a subject of intense controversy. We describe here the different treatment modalities, their benefits and side effects, and the therapeutic strategies that have been tested in the last four decades. Based on this evidence, the current trend is a personalized approach to the patent ductus arteriosus, adapted to each preterm infants individual characteristics and risk factors.