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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.

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A case of a 28-day-old infant who developed suxamethonium apnoea is described. He was found to be homozygous for atypical cholinesterase. Main characteristics of this disorder are reviewed. Other causes of prolonged apnoea in infants recovering from anaesthesia for surgery of pyloric stenosis are discussed.

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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.

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The usefulness and optimal timing of laboratory coagulation tests before obstetric extradural analgesia are controversial. Moreover, the significance of mild coagulation abnormalities during pregnancy remains unclear. We have assessed the reliability of coagulation tests performed several weeks before delivery as predictors of coagulation abnormalities during labour. Platelet count, plasma fibrinogen concentration, prothrombin time (PT) and activated partial thromboplastin time (aPTT) were sampled in 797 women during the ninth month of pregnancy and checked during labour. Platelet count was less than 100 x 10(9) litre-1 for 11 women during labour. Only three had been detected by the first sample. Platelet count less than 100 x 10(9) litre-1 or fibrinogen concentration less than 2.9 g litre-1 during labour were associated with an increase in the incidence of postpartum haemorrhage (odds ratio = 19.7). We conclude that a platelet count several weeks before delivery was not reliable in predicting thrombocytopenia during labour and that women with mild coagulation abnormalities in early labour may need special attention regarding the risk of postpartum haemorrhage.

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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.

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We describe herein a new model of surgical approach of an early mammalian embryo. Indeed the developmental mechanisms of numerous congenital anomalies, such as bladder exstrophy, remain obscure, and progresses in their knowledge must be achieved to propose better treatments. But up to now all the successful reports in experimental models of early produced malformations concerned birds or batracians, whose development is very different from human. We used the rabbit. Twenty-five time matted does were operated at 12.5 days of gestation. Out of their 247 embryos, 99 underwent a surgical procedure. Forty-eight were injured in order to produce an exstrophy. In 18 cases, the embryo extruded from the uterine cavity and could not be reintegrated, and 2 sacs were found empty. The remaining 31 were only exteriorized. Nine additional does received intravenous teratogen at 12.5 days of gestation. In the group of operated embryos we obtained 6 full-term fetuses, one of whom had a cloacal exstrophy. No exstrophy was noted among the intact embryos, neither in the 87 fetuses submitted to the teratogen. We conclude that: it is possible to operate on an early mammalian embryo, and to obtain further growth until term and that the exstrophy we observed in one case resulted from the surgical specific procedure.

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OBJECTIVES: To specify by which means French anaesthesiologists evaluate the haemostasis profile of pregnant women before epidural analgesia. STUDY DESIGN: Nationwide retrospective survey. MATERIAL: Questionnaire sent of 847 French obstetrical units. METHODS: Comparison of categorical qualitative parameters using a chi 2 test. RESULTS: Answers from 435 centres, including 1,834 anaesthesiologists, performing 227 x 10(3) epidurals for 411 x 10(3) deliveries/year were obtained. A preanaesthetic clinical assessment was performed systematically in two out of three units, and blood samples for PT, aPTT and platelet count were taken in more than 90% of the centres. These laboratory examinations were often made during the 9th month of pregnancy (74%). For more than one-third of the anaesthesiologists, biological data are not essential before epidural puncture. In addition, the lower limits considered as being safe before epidural puncture were highly variable between the teams. CONCLUSIONS: Coagulation laboratory tests are almost always ordered before epidural obstetrical analgesia in France. The rationale to perform them is not always related to pregnancy induced haemostatic changes. Therefore, this problem should be clarified by a consensus conference for both practical and economical reasons.

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Methotrexate toxicity is rare but extremely severe. When complete, it consists of ulcerations of the gastrointestinal mucosae responsible for necrotizing enteritis, erythroderma, bone marrow aplasia, interstitial pneumonia, hepatitis and organic renal failure with diuresis. Toxicity is facilitated by pre-existing renal impairment, third sector and abstention or underdosage of foliculinic acid prescribed as antagonist. The diagnosis rests on serum assays, the results of which must be interpreted taking into account the assay method and the time elapsed between the injection of methotrexate and its assay in serum. The multivisceral pathology observed may totally regress, as in the case reported here. Treatment is based on symptomatic measures, starting with maintenance of an abundant and alkaline diuresis, and on the parenteral administration of folinic acid in doses that vary with the authors.

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