[Bronchopulmonary dysplasia-associated pulmonary arterial hypertension of very preterm infants]. / Hypertension artérielle pulmonaire des anciens grands prématurés bronchodysplasiques.

Bronchopulmonary dysplasia (BPD) of very preterm infants is a multifactorial chronic lung disease and its incidence has not decreased despite improvements in neonatal intensive care, including lung protective strategies. Pulmonary hypertension (PH) can complicate the course of BPD. Mortality in infants with BPD-associated PH is thought to be very high, but its incidence is unknown and a standard diagnostic and therapeutic strategy has not been well defined. In this article, we will first describe the current knowledge on the BPD-associated PH and the current treatments available for this pathology. We will then present the HTP-DBP Study, carried out in Paris (France) starting in 2012. The diagnosis of PH is suspected on echocardiographic criteria, but cardiac catheterization is considered the gold standard for diagnosis and evaluation of the severity of PH. Moreover, pulmonary vasoreactivity testing is used to guide the management of patients with PH. The pathogenesis of BPD-associated PH is poorly understood and even less is known about appropriate therapy. Today, optimizing ventilation and reducing the pulmonary vascular tone with specific pulmonary vasodilatator drugs are the main goals in treating HTP-associated DBP. Animal studies and a few clinical studies suggest that medications targeting the nitric oxide (NO) signaling pathway (NO inhalation, oral sildenafil citrate) could be effective treatments for BPD-associated PH, but they have not been approved for this indication. The HTP-DBP study is a French multicenter prospective observational study. The objective is to evaluate the frequency of BPD-associated PH, to describe its physiopathology, its severity (morbidity and mortality), and the effectiveness of current treatments.

Maternal transmission of interstitial 8p23.1 deletion detected during prenatal diagnosis.

We report on the first prenatally diagnosed interstitial 8p23.1 maternally inherited deletion. At 20 weeks of gestation (WG) the fetus was diagnosed with a complete atrioventricular canal. In infancy, the mother underwent a two-step cardiac surgery for an interrupted aortic arch type A associated to an inlet ventricular septal defect (VSD). A straddling of the tricuspid valve type B was confirmed during surgery. The outcome showed no cardiac failure or conduction anomalies. However, she presented with moderate intellectual disability. Classical and molecular cytogenetic studies on amniotic and maternal lymphocytes cells showed a nearly identical interstitial deletion of the 8p23.1 region encompassing the GATA4 gene locus (Mother: nt 6,913,337-12,580,828, fetus: nt 7,074,449-12,580,828) with no modification of the telomeric region. The relevance of our report is not only the maternal syndromic interstitial 8p23.1 deletion, but also maternal transmission which has never been reported before. The maternal and fetal phenotypes were not identical, however, even though they had the same cellular and molecular background: an alteration of the epithelial mesenchymal transition of the atrioventricular valvulo-septal complex where GATA4 plays a positive role in the regulation. We reviewed all cases of interstitial 8p23.1 deletions diagnosed either prenatally or postnatally.

[Aneurism of the subclavian artery associated with Turner's syndrome]. / Anévrisme sous-clavier associé à un syndrome de Turner.

UNLABELLED: Arterial aneurysms associated with Turner's syndrome are rare. CASE REPORT: We report a case of aneurysm of the left subclavian artery in a 16-year-old girl with Turner's syndrome. This patient was operated on: resection of the aneurysm, suture of the aortic arch and reimplantation of the subclavian artery in the left common carotid were performed. At 3-year follow-up, the evolution is favourable. COMMENTS: Cardiovascular anomalies are observed in 50% of subjects with Turner's syndrome. This justifies complementary cardiac investigations in these patients. Congenital malformations (bicuspid aortic valve, aortic coarctation, intracardiac communications, valvular lesions) or acquired anomalies (arterial hypertension, aortic dissection) are frequent. Only one similar case of subclavian artery aneurysm has been reported until now. The risk of rupture justifies the surgical treatment.

[Myocardiopathy and isolated glucocorticoid deficit with ACTH resistance: a fortuitous association?]. / Myocardiopathie et déficit isolé en glucocorticoïdes par résistance à l'ACTH: une association fortuite?

UNLABELLED: Hereditary syndrome of unresponsiveness to ACTH is a rare autosomal recessive disorder characterized by an isolated glucocorticoid deficiency which is exceptionally associated to regressive cardiomyopathy. CASE REPORT: A male newborn had iterative episodes of hypoglycemia since the first hours of life. Acute bronchiolitis at the age of 14 days was associated with transitory dilated cardiomyopathy. Hypoglycemia was due to glucocorticoid deficiency secondary to ACTH insensitivity. Molecular biology showed a composite heterozygotism for the ACTH receptor gene. CONCLUSION: Any congenital glucocorticoid deficiency should lead to search for cardiomyopathy.

A permanent glial precursor cell line, immortalized with the adenovirus E1A gene, undergoes apoptosis in restrictive growth conditions.

We have previously described some differentiation properties of the ERD.1.1 cell line, obtained after transfer and integration of the adenovirus-5 E1A gene. Depending on the growth conditions, these cells differentiate towards the astrocyte or early oligodendrocyte differentiation pathway. However, in growth restrictive conditions, we observed dying cells that detached from the monolayer constituted of differentiating cells. This led us to examine the characteristics of the dying cells. The study of the low-molecular-weight DNA and the ultrastructural examination of chromatin showed that these cells were undergoing apoptosis. The results also suggest that the expression of an integrated polyoma middle T gene can partly save the cells from apoptosis.

Immortalization of different precursors of glial cells with a targeted and temperature-sensitive oncogene.

Different types of glial precursor cell lines were obtained after stable transfection of brain cells with the pJC-SVLTtsA vector carrying the tsA58 simian virus 40 large T (SVLT) gene driven by the promoter of a gliotropic strain of JC papovavirus. The immortalized cells were conditional for growth: they expressed the SVLT antigen and proliferated at 34 degrees C, but their growth was either reduced or arrested when they were shifted to 39 degrees C. The differentiation characteristics of four representative lines were more extensively studied. The CR15 and CM8 lines displayed properties of bipotential glial progenitors: they were able to express oligodendrocyte markers at both temperatures, but could differentiate into astrocytes only at 39 degrees C. In contrast, the CR19 and CM3r lines corresponded to more committed oligodendrocyte precursors: they expressed various oligodendroglial markers but they could not synthesize the glial fibrillary acidic protein. More particularly, the CM3r mouse cells displayed a typical oligodendrocyte progenitor morphology and expressed the proteolipid protein mRNA.

Proliferation and differentiation properties of bipotent glial progenitor cell lines immortalized with the adenovirus E1A gene.

Bipotent glial progenitors have been immortalized by the transfer of the adenovirus E1A gene into primary cultured cells from embryonic rat brain. The lines obtained are phenotypically untransformed, retain growth contact-inhibition, and are able to differentiate, unless they are surtransfected with transforming oncogenes. Depending on the growth conditions, these immortalized cells express differentially either oligodendrocyte or astrocyte-specific markers and genes. After being seeded in serum-free medium, they display gangliosides recognized by A2B5 monoclonal antibody, and then they express sequentially O4 epitopes, galactocerebroside, and the myelin protein DM20. When grown in serum-supplemented medium, the cells express at first A2B5 epitopes, and then transiently O4 and galactocerebroside; after reaching confluence, O4 and galactocerebroside become undetectable, whereas the cells begin to coexpress glial fibrillary acidic protein and glutamine synthetase. These results indicate that the cell lines can undergo a differentiation reminiscent both of O-2A progenitors and of plastic process-bearing glial subpopulations. The cells were also genetically marked by the stable introduction of the nlslacZ reporter gene. Thus, the lines could be useful for studying direct interactions in vitro, or for post-grafting investigations. They should also provide a model for studying the mechanisms involved in the commitment and in the control of proliferation and differentiation of this cell lineage. This suggestion is consistent with the data indicating a growth arrest-dependent differential expression of a novel gene encoding a protein with a helix-loop-helix domain.

Establishment of permanent astroglial cell lines, able to differentiate in vitro, from transgenic mice carrying the polyoma virus large T gene: an alternative approach to brain cell immortalization.

Permanent untransformed cell lines have been established from the cerebral cortex of transgenic mice that carry the polyoma virus large T gene. The immortalized cells described here synthesize laminin and neural cell adhesion molecules and induce primary neurons to develop neuritic processes. As shown by immunofluorescence and immunoblotting assays, they begin to synthesize the glial fibrillary acidic protein (GFAP) after confluence. Double labelling experiments indicated that GFAP expression is reversibly correlated with the arrest of cell division. The present cells also display adrenergic, serotoninergic, and high levels of muscarinic receptors coupled to the phosphatidylinositol signalling pathway. Taken together, our data show that these cell lines constitute homogeneous cell material that has retained the main differentiative, functional, and growth properties of normal astrocytes. Therefore, such clonal untransformed cell lines should be useful for further molecular studies, addressing terminal differentiation of glial cells, glioneuronal interactions, and astroglial expression of receptors for neurotransmitters. Furthermore, we suggest that this approach of cell immortalization by the use of transgenic mice carrying a non-transforming oncogene might be extended to a variety of cell types.

Immortalization of bipotential and plastic glio-neuronal precursor cells.

Permanent clonal cell lines from newborn mouse striatum have been established after transfer of the simian virus 40 large tumor oncogene by means of a retroviral vector. Some of the lines obtained displayed properties of bipotential and plastic glio-neuronal precursors. Depending on the culture conditions, these cells express either the glial fibrillary acidic protein or neurofilaments. In addition, the cells can display adrenergic, D1 and D2 dopaminergic, muscarinic, and 5-hydroxytryptamine type 2 serotoninergic receptors, which are coupled either to the adenylate cyclase or to the phosphatidylinositol signaling pathways. The panel of receptors for neurotransmitters exhibited by these lines closely resembles that of primary striatal neurons. Results suggest that plastic common precursors of astrocytes and neurons persist in the striatum at a late developmental stage. As these permanent cell lines constitute an unlimited source of homogenous cell material, we suggest that they should be useful for molecular and pharmacological studies on the mechanisms and regulation of signal transduction as well as the commitment, plasticity, and differentiation of neural cells.

Value of radionuclide assessment with thallium 201 scintigraphy in carnitine deficiency cardiomyopathy.

The case of a 30 month-old boy who presented with isolated severe dilated cardiomyopathy is reported. The diagnosis of systemic carnitine deficiency was confirmed by low serum and tissue carnitine levels. During oral L-carnitine therapy, dramatic improvement of the cardiac function was assessed by radionuclide methods. Myocardial thallium 201 uptake was closely correlated with cardiac function studied by angioscintigraphy. These methods are simple, easily reproducible, non-invasive and involve little radiation. In a case of cardiomyopathy, we suggest an immediate trial of oral carnitine treatment; the efficacy of the therapy can be confirmed by isotopic tests with thallium 201 scintigraphy.

[A rare cause of neonatal ulcero-necrotizing enterocolitis: aortic coarctation syndrome]. / Une cause rare d'entérocolite ulcéro-nécrosante néo-natale: le syndrome de coarctation aortique.

The authors report a case of necrotizing enterocolitis which appeared in the first hours of life of a full-term neonate without signs of sepsis. This neonate presented with a severe hypoplasia of the horizontal aorta and very tight coarctation responsible for hepatic, renal and mesenteric ischemia. Reports of enterocolitis as a complication of congenital heart disease are rare and related most often to hypoplastic left heart than to coarctation of the aorta.

[Coronarocardiac fistula disclosed neonatally. Apropos of 2 cases]. / Fistules coronaro-cardiaques à révélation néo-natale. A propos de deux observations.

Two cases of fistula between a coronary artery and the cardiac cavities (right coronary artery-right atrium, and right coronary artery-right ventricle) are reported. They were revealed by cardiac failure developed shortly after birth. The diagnosis was confirmed by two-dimensional echocardiography and angiography. In both cases closure of the fistula, with atriotomy in one case and coronary arterotomy in the other case, could be performed before the age of 1 month. The post-operative result was satisfactory in the two infants. Cases in which blood flow through such fistulae is important enough to cause cardiac failure in the newborn are exceptional. Nevertheless, this diagnosis must be borne in mind, as it requires rapid surgical correction.

[Regressive hypertrophic myocardiopathy in an infant with Recklinghausen's neurofibromatosis]. / Myocardiopathie hypertrophique régressive chez un nourrisson atteint d'une neuro-fibromatose de Recklinghausen.

A case of neonatal hypertrophic cardiomyopathy (HCM) without obstruction is reported. Von Recklinghausen neurofibromatosis in the mother and several relatives and the occurrence of café-au-lait spots in the child at 6 weeks of life led to the association of HCM with this phacomatosis. The spontaneous regression of the myocardial hypertrophy after 6 weeks makes this first report of neonatal HCM in the course of Von Recklinghausen neurofibromatosis peculiar. Several reports in the literature mention the possibility of such a spontaneous regression of HCM or diffuse cardiac tumors, especially in the course of phacomatosis.

[Outcome of infants operated on for aortic coarctation before 3 months of age]. / Devenir des nourrissons opérés avant 3 mois d'une coarctation aortique.

Between January 1966 and June 1982, 177 infants less than 3 months of age underwent surgical cure of coarctation of the aorta. Seventy-one percent had associated cardiac lesions not including a patent ductus arteriosus. With the cure of the coarctation either by resection anastomosis or angioplasty, 45% underwent associated surgical procedure, mainly pulmonary artery banding. Early mortality was 26% for the last 4 years of the study. Early deaths, significantly correlated with the severity of the preoperative heart failure and the importance of pulmonary hypertension, were not correlated with an associated heart disease. Of the 95 survivors operated on before December 31, 1981 and with a long follow-up, 18 died later on. Late deaths are related with associated cardiac malformations. Thirty-nine (41%) of the survivors had recurrent coarctation. This was correlated with the year of surgery and not with the surgical technique. In cases with coarctation of the aorta surgical cure should not be withheld before age 3 months, when there is heart failure, with or without associated cardiac malformations. The mortality, even in isolated coarctation (6%), the occurrence of sudden deaths after good surgical repair, the frequency of recoarctations lead to suggest that in infants under 3 months of age, careful supervision and conservative medical treatment should be considered, if the coarctation is isolated and well tolerated.