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Biomedical subjects

F Bargy

Publications and source records attributed to F Bargy.

At least 19 recordsLinked to original sources

Preclinical studies for cell transplantation: isolation of primate fetal hepatocytes, their cryopreservation, and efficient retroviral transduction.

Fetal hepatocytes are an attractive target for in utero cellular transplantation. Their use could provide a very efficient way for implanting normal or transduced cells into the livers of affected fetuses. Marking cells with recombinant retroviruses is a powerful tool for evaluating the chimerism of grafted animals. The technique relies on the ex vivo transduction efficiency of the engrafted cells. We have isolated fetal primary hepatocytes from nonhuman primates. The cells were cultured and transduced with a retroviral vector carrying the Escherichia coli beta-galactosidase gene. Optimal gene transfer efficiency was obtained 48-60 hr after plating and was as high as 90%. Cryopreservation had little effect on cell viability and infectivity: The viability of thawed hepatocytes remained high (75-85%) and the infection efficiency was identical to that of freshly isolated cells. Efficient ex vivo retroviral gene transfer into fetal hepatocytes provides an appropriate system for testing allogenic grafting and for modifying immunogenicity of engrafted cells. These results open up new perspectives for cell transplantation through cell banking.

Animals

[Hernia in children].

Congenital hernia seems to be the right term to define "hernia in childhood". Especially in newborn and infant, it is possible to observe numerous different pathologies which have nothing in common apart their congenital origin. Some as inguinal or umbilical hernia are very commonly encountered and others us omphalocele, gastroschisis or diaphragmatic hernia are quite rare and involved in the field of prenatal diagnosis and neonatal surgery.

Abdominal Muscles

Anatomical basis of a common embryological origin for epispadias and bladder or cloacal exstrophies.

Epispadias, bladder exstrophy and its variants are in the first place usually considered as urological anomalies. Embryological theses and therapeutic approaches are mainly based upon this aspect. We challenge this point of view, in order to bring out a new axis of research about this still misknown pathologic field. A review of 16 cases of bladder exstrophy, 6 epispadias cases, and one cloacal exstrophy case, which had never been described before, revealed that the almost constant bony defect of the pelvic ring was linked with the severity of the visceral features, and with the continence status in epispadias cases. The commonly admitted theories about exstrophy development are based on a primary defect of the cloacal membrane. We suggest that the first anomaly could lie in a lack of rotation in the pelvic ring primordia.

Bladder Exstrophy

[Towards gene therapy in familial hypercholesterolemia].

Familial hypercholesterolemia (FH) is an inherited disease caused by a defect in the gene encoding the Low Density Lipoprotein receptor (LDL-R). The ex vivo hepatic gene therapy which restore the expression of the normal protein in hepatocytes should correct the disease. Improved transduction efficiency and long lasting expression of the transduced gene remain the main goals of gene therapy research. We developed an efficient and reliable method for in vivo transduction of human, mouse and primate primary hepatocytes. A retroviral vector bearing the LDL-R cDNA driven by the liver-type pyruvate kinase promoter allows high and tissue specific expression of the gene in primary hepatocytes. A second vector with a housekeeping promoter corrects the LDL-R deficiency in fibroblasts from a FH patient. Ex vivo preclinical studies in non-human primates will provide new insight in transduced cells biology after reimplantation.

Animals

Gastroesophageal reflux after repair of congenital diaphragmatic hernia.

Seventy-four survivors of congenital diaphragmatic hernia (CDH) repair were reviewed for gastroesophageal reflux (GER). Twenty-nine patients had a prenatal diagnosis of CDH, 31 had the diagnosis established during the first 60 minutes of life, and 14 had a late diagnosis. Fifty-seven of the 60 patients with a prenatal diagnosis or diagnosis at birth had their CDH repaired during the first 24 hours of life. Thirty-six of the 37 patients with clinical signs of GER and 10 patients without typical clinical signs had documented GER. The overall incidence of GER was 62% (46 of 74). The 46 comprised 22 of the 29 patients (75.8%) with a prenatal diagnosis of CDH, 21 of the 31 (67.7%) with a diagnosis at birth, and 3 of the 14 with a late diagnosis. Eleven patients had surgical treatment of GER. A significant correlation was found between GER and the preoperative thoracic position of the stomach (32 v 8, GER+ v GER-; P < .01) and GER and the prenatal diagnosis of CDH (22 v 7, GER+ v GER-; P < .01). Duration of artificial ventilation (68.97 +/- 15.33 days v 14.14 +/- 3.89 days, GER+ v GER-; P < .005) and duration of hospitalization (22.04 +/- 3.59 weeks v 3.9 +/- 0.88 weeks, GER+ v GER-; P < .0003) were significantly longer for the patients with pathological GER. To decrease the morbidity related to GER, we propose using diaphragmatic patches during hernia repair to lower the strain on the crus, and using parietal patches to lower intraabdominal pressure after reintroduction of the herniated viscera.

Female

Gastroesophageal reflux in neonates with congenital abdominal wall defect.

Gastroesophageal reflux (GER), not yet described as a real complication, takes place very often in neonates with congenital abdominal wall defect. Our aim was to determine whether it is due to abdominal hyperpressure alone, or if another factor is involved in this occurrence. Thus we studied one group of 80 gastroschises and one of 67 omphaloceles, treated in our department between December 82 and December 92. Overall occurrence was found to be about 50% in both groups. The main feature is the particular severity of GER in neonates with wide omphalocele who required staged closure, leading to further surgical antireflux procedure. We suggest that this procedure could be performed earlier, at the time of closure, for these babies in whom moreover the anatomic approach is favorable.

Abdominal Muscles

[Fetal surgery].

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Animals

Amniotic fluid digestive enzymes: diagnostic value in fetal gastrointestinal obstructions.

The diagnostic value of amniotic fluid gamma-glutamyl-transpeptidase (GGTP) and intestinal alkaline phosphatase (iALP) was evaluated in 55 patients who underwent amniocentesis for karyotyping because fetal gastric or small bowel dilatation had been detected by ultrasound. Gastrointestinal malformation was confirmed in 46 cases and there was no gastrointestinal anomaly in nine cases. Prenatal ultrasound was suggestive of gastroduodenal dilatation in 34 cases (group I) and small bowel dilatation in 21 cases (group II). In group I, amniotic fluid GGTP above the 99th percentile was 71 per cent sensitive and 100 per cent specific for a true anatomical defect of the digestive tract (mainly duodenal atresia). In group II, high levels of GGTP and/or iALP were 69 per cent sensitive and 83 per cent specific for a fetal digestive tract anomaly. In other words, when digestive tract dilatations were diagnosed by prenatal sonography, abnormal amniotic fluid enzyme activities were strongly suggestive of such an anomaly, the possibility of which was not precluded by normal amniotic fluid iALP and GGTP activities. But amniotic fluid digestive enzyme activities do not help in defining the prognosis.

Alkaline Phosphatase

Longus colli has a postural function on cervical curvature.

To determine the postural role of longus colli (LC) and dorsal neck muscles, we have studied the relationship between their cross-sectional areas related to their force of contraction and the lordosis and the length of the cervical spine. This study was carried out in 36 healthy subjects. Muscle cross-sectional areas were measured by computerized tomography. The index of lordosis and the length of the cervical spine were measured on an X-ray profile. The cross-sectional area of LC was correlated to the lordosis index (R = -0.432, p < 0.02) whereas all the other parameters were not correlated. The authors conclude that LC counteracts the lordosis increment related to the weight of the head and to the contraction of the dorsal neck muscles. Postural functions of LC and postcervical muscles are complementary. They form a sleeve which encloses and stabilizes the cervical spine in all positions of the head.

Adult

Management of ovarian cyst detected by prenatal ultrasounds.

As a result of refinements in Prenatal Ultrasonography (US), neonatal ovarian cysts are more frequently encountered than in the past. Between January 1981 and December 1990, 21 consecutive fetuses with ovarian cysts were followed up by ultrasonography. 23 ovarian cysts were diagnosed between 28 and 38 weeks gestation. 18 cysts were initially large cysts (more than 50 mm in diameter). In 9 cases, an anechoic cyst was observed and a US-guided needle aspiration of the cyst was performed (2 antenatally and 7 postnatally). Ultrasonographic patterns of complicated cyst were observed in 3 fetuses. After a postnatal ultrasound control, 11 infants were operated on: 8 surgical interventions were required for complicated cysts (torsion: 4, hemorrhage: 4), 3 cases irrespective of their sonographic appearance in our initial experience. In the remaining cases, spontaneous resolution was followed by repeated ultrasonographic examination. Prenatal ultrasonography today allows diagnosis of ovarian cysts and may suggest antenatal complications. To preserve as much ovarian tissue as possible, cysts greater than 50 mm in diameter should be candidates for percutaneous aspiration and complex cystic masses should be operated on.

Female

Venous territories of the brain.

The venous return of the cerebral hemispheres is ensured by two systems. The first, superficial system, reaches the peripheral dural sinuses, i.e. the superior sagittal sinus, the lateral sinus and the cavernous sinus. The second, deep system, corresponds to Galen's vein. Anatomical and angiographic data from the literature enable the usual drainage territory to be defined for each of these collecting vessels. However, the variability of the superficial sylvian vein and the importance of cortical anastomotic vessels make impossible to delimit precisely the territory of each peripheral sinus. The functional role played by numerous centro-peripheral anastomoses is more difficult to assert in each individual. It is therefore probable that in the cerebral hemispheres there is a deep territory balancing the superficial territories.

Cavernous Sinus

[Evaluation of 5 years of experimental in utero surgery for the repair of diaphragmatic hernia].

The incidence of diaphragmatic hernia in he newborn is 1:2,500 to 5,000 births. An extensive American programme of foetal surgery for in utero repair of this defect has shown that the pulmonary hypoplasia was due to compression of lung tissue by the herniated organs. This process could be interrupted be repairing the diaphragmatic defect early enough in utero (before the 28th week). The results of five years of experimental surgery for in utero correction of diaphragmatic hernia are presented here. The experimental model used was the Macaca fascicularis monkey, the pregnant female of which having several gestational and endocrine characteristics similar to those of the pregnant woman. Three different experimental programmes were carried out successively. A first series including five animals was used to experiment both surgical and anaesthetic techniques; three foetuses died in utero. The second series (10 animals) was designed to find a suitable protocol for tocolysis. One female died after surgery, and seven other foetuses also died. The third group (13 animals) was the main study group. The diaphragmatic hernia was first created surgically, and then repaired. No foetus died from the surgery. One female died before giving birth, and one offspring died shortly after birth as its mother had no milk. After the encouraging results obtained with this last series of animals, the procedure was applied to human cases, with the Hospital Ethical Committee's approval. In the first case, the foetus died postoperatively as a result of the rupture of the diaphragmatic prosthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General

[Fetal surgery: for what purpose?].

Widespread use of prenatal ultrasonography allows accurate diagnosis of many fetal malformations. The natural history and pathophysiology of some fetal diseases will undoubtedly induce lethal issue. Prenatal ultrasounds allow to determine prognosis during the second trimester of pregnancy. Experimental model and clinical practice have shown that prenatal surgery could be proposed for some correctable malformations: congenital diaphragmatic hernia, cystic adenomatoid lung disease, sacrococcygeal teratoma, lower urinary tract obstruction. To purpose this fetal therapy, great attention has to be paid to maternal risk and her future fertility, keeping in mind the aim of such fetal surgery: a new hope for improved management of the fetus with life-threatening defect.

Congenital Abnormalities

Method of quantitative anatomical study of the dorsal neck muscles. Preliminary study.

Biomechanical models of the cervical spine require knowledge of the position, size and orientation of the individual muscles that act on the cervical spine. We have developed a technique to stereometrically measure anatomical specimens. The apparatus is composed of three graduated metallic rods, which slide along a fixed support. This method is accurate to map the anatomy of individual muscles and provides quantitative data on their lines of action. Results are obtained from one specimen. The computer processing of the collected data allows formulation of a three-dimensional model of the neck muscles in man.

Biomechanical Phenomena

The anatomy of intersexuality.

A description of anatomical lesions in the intersexual states has been made based on clinical and anatomical observations. This study provides the anatomical basis which is necessary before surgical genital reconstruction can be carried out.

Disorders of Sex Development

[Meconium peritonitis. The value of prenatal diagnosis].

Over an eight year period (1980-1987), fifteen cases of meconium peritonitis have been studied. As it has been reported, this pathology is still very rare. Ten pregnancies have been followed on by multiple échographies and the prenatal diagnosis of meconium peritonitis, suspected as early as 24 weeks of amenorrhea, has been established in ten cases. Among these, eight infants have been operated on before twelve hours of life, and for the ninth, surgical treatment was not advocated. The most frequent cause of the pathology is a perforation above a bowel obstruction. Two had cystic fibrosis. Of the 15 infants with meconium peritonitis, nine survived, and among these, one with cystic fibrosis and the one that has not been operated. Prenatal diagnosis in meconium peritonitis is of major interest in taking care early infants that will need an urgent surgical operation in most cases.

Diagnosis, Differential