Sylvie Beaudoin

Fetal Lung Growth in Congenital Diaphragmatic Hernia

Background: In spite of significant therapeutic progress, the prognosis of congenital diaphragmatic hernia (CDH) remains pejorative in those forms in which the liver is herniated into the chest. The severity of this malformation relies on the pulmonary hypoplasia due to lung compression by the herniated viscera in the thoracic cavity, particularly the liver. This impaired growth concerns the whole pulmonary tissue, i.e. both the vessels and the alveoli. For the clinician, it is mandatory to know the evolution pattern of the lesions, to define the best time to treat them. Aim and Method: The aim of this work was to study the pulmonary lesions along the gestation in fetuses affected byCDH. This morphological study was carried out on 134 human fetuses aged from 22 to 40 weeks of gestation. Anatomical and histological analysis focused on lung weight, alveolar count and wall thickness of the distal vessels. Results: The results indicate that the pulmonary lesions worsen as the pregnancy continues, particularly beyond 30 weeks of gestation. Conclusion:Such an anatomical study should bring to the clinicians useful data to enhance the management of the patients.

Developmental Stages in the Rabbit Embryo: Guidelines to Choose an Appropriate Experimental Model

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth.

Mediastinal fetus in fetu. Case report and embryological discussion.

Fetus in fetu is an extremely rare condition defined by the presence of both axial skeleton and organoid formations in the parasitic mass. Besides some authors assuming that fetus in fetu and highly-differentiated teratomas are part of the same pathogenic spectrum, it has been emphasized that these criteria indicate a rather different embryogenetic mechanism. We herein report the first case to our knowledge developed in the ventral mediastinum that was thought to be a tumor before birth. The literature is reviewed and we propose a new explanation for the development of this rare anomaly, based on a defective implantation.

In utero allotransplantation of retrovirally transduced fetal hepatocytes in primates: Feasibility and short-term follow-up

In utero allotransplantation of fetal hepatocytes into a preimmune fetus could be used in early treatment of many inherited hepatic metabolic diseases. This study was designed to assess the tolerance to hepatocyte transplantation and to test the feasability and toxicity of such an injection in a primate model. Fetal hepatocytes were obtained from two 120-day-old Macaca mulatta fetuses and cryopreserved. They were thawed, cultured in vitro, and transduced with a recombinant retrovirus expressing beta-galactosidase. Transduction efficiency was 75-85%. Three unrelated fetuses (90, 100, and 104 days old) were each given 1-2 x 10(7) transduced cells via the umbilical vein. This caused vasospasm and severe bradycardia. Two fetuses died in the 48 hours after transplantation; the third survived and was killed at the end of gestation. No evidence of the infused cells was found. Three fetuses (90 days old) were, therefore, given 3-4 10(7) hepatocytes by direct intrahepatic injection. All the fetuses survived without side effect. Donor cells were not apparent from histochemical staining and PCR reactions. There was no evidence of inflammatory reaction. These findings indicate that the protocole could be improved by increasing the number of transplanted cells and using specific hepatic promoters in the retroviral vectors to achieve an effective postnatal chimerism.

Deeper rectal biopsies and better yield of neuronal structures with Scheye vs Noblett forceps—preliminary results

OBJECTIVE The aim of the study was to compare 2 different forceps designed to perform biopsies of the rectal mucosa, those of Noblett and Scheye, the latter having a similar design and differing by the disposable cutting system. METHODS This historical study compares biopsies obtained with the Noblett forceps in 13 girls and 20 boys (mean ± SD age, 13 ± 30 months) and biopsies obtained with the Scheye forceps in 19 girls and 21 boys (mean ± SD age, 8.5 ± 19 months). RESULTS The thickness of the material obtained with the Scheye forceps was significantly greater for the specimens obtained with the Scheye forceps (total biopsy: 1.74 ± 0.46 mm vs 0.67 ± 0.2 mm, P < .0001; submucosa: 1.12 ± 0.4 mm vs 0.14 ± 0.17 mm, P < .001). The Scheye forceps considerably increased the yield of neuronal structures, both for submucosal plexus (P < .003) and ganglia (P < .0001). No complication occurred in either group. CONCLUSION The Scheye disposable rectal biopsy system provides larger mucosal biopsy samples than the Noblett with increased recovery of neuronal structures.

In utero Allotransplantation of Fetal Hepatocytes in Primates

Objective: Because intrauterine transplantation of fetal hepatocytes could become an effective approach for treating severe genetic disorders of the liver, the objective of this study was to demonstrate the feasibility of in utero allotransplantation of fetal hepatocytes in a nonhuman primate model using direct intraparenchymal administration of donor cells. Methods: Fetal primary hepatocytes were isolated from 3 fetal primates (Macaca mulatta) at 89–120 days of gestation, and cryopreserved. When a recipient was available, the cells were thawed and transduced by a β-galactosidase-expressing retrovirus (3 cases) or labelled with a fluorescent dye (4 cases). Hepatocytes were infused directly into the fetal liver under surgical visual control. Engraftment was assessed by surgical liver biopsies taken 8–60 days following transplantation. Results: Six recipients survived until liver biopsy, and 1 died during the surgical procedure. There was no evidence of engraftment in the 3 fetuses that received genetically marked hepatocytes. All 3 monkeys who received 20–25 × 106 hepatocytes from an 89-day-old donor labelled with fluorescent dye had positive liver biopsies 8–11 days following intrauterine transplantation. Conclusions: In utero allotransplantation of fetal hepatocytes is feasible in the nonhuman primate, and direct intraparenchymal administration enables short-term detection of persisting donor hepatocytes.

Surgical Approach of an Early Mammalian Embryo: The Rabbit Model

We describe an experimental surgical model in early rabbit embryo (12.5 days of gestation). Twenty-one embryos were operated, of which 9 survived the first postoperative week and 5 had normal further growth until term. As far as we can ascertain, this is the first successful report of a surgical approach in early mammalian embryos. We think that this model may be useful for workers involved in the study of early congenital malformations.

Insights into the etiology and embryology of gastroschisis

The development of gastroschisis has long remained an area of interest and controversy. Successive theories about its pathogenesis are herein reviewed and discussed. Two historical assumptions, that omphalocele results from a persistent umbilical hernia, and that gastroschisis does not involve the umbilical cord, are dismissed. Therefore, one can envision gastroschisis for what it is, i.e. a ruptured physiological hernia. The causal agents for this intrauterine accident to occur are yet to be determined. Further bowel damage and complications can be explained by the mesenteric insult.

Meconium peritonitis in both fetuses with early twin-to-twin transfusion syndrome.

Twin-to-twin transfusion syndrome (TTTS) is due to unbalanced inter-twin bloodflow through placental vascular anastomoses. We present a TTTS case treated with fetoscopic laser photocoagulation (FLP) that was complicated by perinatal meconium peritonitis in both twins. Ten weeks following laser treatment, the two fetuses showed intra-abdominal hyperechogenicity and ascites. After birth, the two newborns were surgically managed for peritonitis. We discuss the pathogenesis of this double insult. The present case highlights the role of end-circulation bowel thrombi as the potential cause of subsequent intestinal perforation.

P258 - Diagnostic anténatal des omphalocèles et malformations associées

Objectifs Apprecier la sensibilite de l’echographie antenatale au diagnostic de l’omphalocele et au depistage des malformations associees et l’impact consecutif sur le taux de survie. Materiels et Methodes Etude retrospective de 91 enfants operes d’une omphalocele a l’Hopital de Saint Vincent de Paul entre 1985 et 2005. Nous les avons classes en deux groupes: omphalocele de type 1 (49 cas), type 2 (42 cas). Resultats La sensibilite de l’echo-antenatale au diagnostic est plus faible pour le type 1:52 % contre 96 % pour le type 2 et sa fiabilite pour le depistage des malformations associees a ete plus faible dans le groupe 1: 50 % contre 68 % dans le groupe 2. Le taux de survie a ete considerablement ameliore pour le groupe 2 entre les deux periode d’etude 1985-1992 et 1993-2005 (80 % a 100 %) par contre la mortalite dans le groupe 1 n’a pas change (8 %). Conclusions Les omphaloceles de petite taille ont un diagnostic antenatal difficile et tardif alors que ceux de grande taille ont un diagnostic antenatal plus facile est plus precoce ce qui permet un depistage precoce des malformations associees, et par consequence l’amelioration de taux de survie grâce a la programmation de l’accouchement dans des centres specialises et l’elimination des naissances porteuses des malformations severes.