[Preterm labour after adenosine treatment for paroxysmal supraventricular tachycardia during pregnancy, a case report]. / Menace d'accouchement prématuré après administration d'adénosine pour la réduction d'une tachycardie supraventriculaire paroxystique à 30 semaines d'aménorrhée : à propos d'un cas.

Paroxysmal supraventricular tachycardia is the most frequent arrhythmia among young pregnant women. In case of failure of vagal manoeuvres, their management is preferentially intravenous infusion of adenosine. The in vitro contracturant effect of adenosine on myometrial fibres is known, but very few data are available about the in vivo effect during pregnancy. We report here the case of a 30-week gestational age pregnant woman treated successfully by adenosine for a junctional tachycardia. Adenosine administration was immediately followed by a preterm labour managed by calcium channels blockers tocolysis. Even if causal relationship remains uncertain, this observation is consistent with physiopathological data and should catch physician's attention when initiating this treatment.

[Implementing palliative care for newborns in various care settings. Part 3 of "Palliative care in the neonatal period"]. / La mise en oeuvre pratique des soins palliatifs dans les différents lieux de soins : 3(e) partie des réflexions et propositions autour des soins palliatifs en période néonatale.

Palliative care in newborns may take place in the delivery room and then continued either in maternity wards or in the neonatal unit. For babies developing a chronic condition, going home may be advantageous. The population concerned includes babies born with a severe intractable congenital malformation and certain extremely preterm newborn babies at the limits of viability. Care procedures as well as withholding and withdrawing treatments are reviewed.

[Access to preventative care, screening and treatment of women in vulnerable socio-economic groups presenting with cervical cancer]. / Cancer du col et précarité, accès aux soins diagnostic et traitement.

AIM: The object of this study was to evaluate access to preventative care, screening and treatment of women in vulnerable socio-economic groups presenting with cervical cancer and the progression of their disease. METHOD: This is a retrospective study of 123 patients with cervical cancer treated at the hôpital Bichat (Paris) or the hôpital Verdier (Bondy) between 1st January 1996 and 31 December 2005. RESULTS: "CMU" or "AME" is the entitlement for fully state funded medical care and was used in this study to indicate social deprivation. Social deprivation is associated with homelessness (43.9 vs 1.23%; P = 0.0001) and unemployment (90 vs 30%; P = 0.0001). Women from deprived groups seldom enter screening programs (25 vs 56.1%; P = 0.008). Once symptomatic they delay seeking medical attention (1.8 months later than for non-deprived groups; P = 0.027), present more often to accident and emergency departments (51.22 vs 17.07%; P = 0.0003), and do not see any primary care practitioner (41.46 vs 8.64%; P < 0.0001). There was no significant difference with regard to treatment instituted in the two groups. The non-deprived patients residing in Bondy had similar access to care as the deprived patients treated in Paris. The average follow-up period was 30.43 months (+/- 26.64). CONCLUSION: Cervical screening is not taken up adequately throughout the general population. Access to health care is poorly tailored to the needs of the socially deprived. Social deprivation did not demonstrate an association with levels of pelvic recurrence, metastasis or death. The low doctor to patient ratio in certain geographical areas reduces access to medical care.

[What's new in fetal medicine?]. / Quoi de neuf en médecine foetale?

One of the major progress in fetal medicine in recent years is the increased sensitivity of sonographic screening for foetal malformations, due to technical improvement but also to a better training of professionals. Screening for chromosomal abnormalities is no longer based on maternal age alone. Second trimester maternal serum screening (MSS) is increasingly used: thus in 1997, 376,798 MSS tests were performed in France, yielding to the prenatal diagnosis of 391 cases of Down's syndrome. First trimester sonographic nuchal translucency measurement (NTM) is an effective screening method when performed under stringent conditions. Quality control however, is more difficult to implement on a large scale for NTM than for MSS. Performing screening tests sequentially carries a danger of generating an unnecessarily high number of amniocentesis, which may be obviated by a rational calculation of an individual's risk to carry an aneuploid baby. First trimester MSS is expected to become standard practice in the next years, probably in combination with NTM. Cytogenetics underwent substantial innovations recently, due to the ever-increasing use of molecular cytogenetics. FISH techniques allow: 1) precise analysis of unexpected structural chromosomal abnormalities diagnosed by routine amniocentesis, 2) rapid screening of the most common aneuploidies by amniocentesis when a fetal structural anomaly is detected by 3rd trimester ultrasound, 3) diagnosis of micro-deletions suspected by fetal ultrasound or post-mortem. Prenatal diagnosis by maternal blood sampling and fetal cells or DNA analysis is now part of routine clinical practice in selected cases, such as fetal sexing in families affected by an X linked disease. Thus one can select those pregnancies eligible to invasive prenatal diagnosis. Pre implantation diagnosis, which has not been legal in France until 1999 is now increasingly used as an alternative to first trimester diagnosis. As for fetal therapy, a major recent breakthrough is the prenatal management of twin to twin transfusion syndrome by either amnioreduction or laser coagulation of inter-twin vascular shunts. In addition, new pathophysiologic concepts involving the renin angiotestin system could lead to further therapeutic innovations. A European randomised trial is now being completed to establish the respective indications of drainage and Laser. All this underscores that fetal medicine is no longer solely a succession of dramatic technical breakthroughs, but is entered an era of large-scale diffusion that requires evidence based evaluation.

Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases.

BACKGROUND: The transplantation of isolated hepatocytes in large animals, including nonhuman primates, must be evaluated before clinical trials are performed. However, in the absence of large transgenic animals and large-animal (as opposed to small-animal) models of genetic deficiencies, it is difficult to evaluate the fate of transplanted hepatocytes, their localization, survival, and function within the parenchyma of the host liver. In this work, we aimed to develop a technique for delivering hepatocytes to the liver of a nonhuman primate and to evaluate their localization and functionality in the short term. METHODS: A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis) and hepatocytes were isolated. Hepatocytes were labeled in vitro with a recombinant retrovirus expressing the beta-galactosidase gene and returned to the liver by infusion through a portal catheter left in place. Liver biopsies were performed 4 and 7 d after transplantation. RESULTS: Twenty-four monkeys underwent surgery to define the necessary technical adjustments and to optimize conditions. Six monkeys died. The whole protocol, including the transplantation of genetically marked hepatocytes and procurement of liver biopsies, was performed in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes expressing the beta-galactosidase gene were widely distributed in the portal tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after transplantation. CONCLUSIONS: We have developed an experimental nonhuman primate model for the evaluation of hepatocyte transplantation. We demonstrated the engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7 d after transplantation.

[Allotransplantation in utero and immortalization of primate fetal hepatocytes]. / Allotransplantation in utero et immortalisation d'hépatocytes foetaux de primates.

We are developing cell therapy approaches on non-human primates as a preclinical model for the treatment of hepatic metabolic diseases. In foetuses, the tissues, including liver, are in expansion, which should facilitate hepatocytes engraftment, and the immune system becomes fully mature only after birth. We have set out conditions for isolation of fetal hepatocytes from macaca mulatta at the end of the 2nd trimester of gestation (90-100 days), their cryopreservation and retroviral transduction. Two different routes of administration of hepatocytes were evaluated: the umbilical vein which was deleterious for the foetuses, and the intraparenchymatous injection which was well tolerated by the animals. Administration of hepatocytes into the hepatic parenchyma resulted in microchimerism and allogenic cells were visualized 9 days after transplantation. Another approach has been to immortalize simian foetal hepatocytes using a retroviral vector expressing SV40 Large T flanked by lox sites. A cell line has been established for 2 years, which is not tumorigenic when injected subcutaneously into nude mice and display characteristics of bipotent hepatoblasts, precursors of hepatocytes and biliary cells. After orthotopic transplantation into nude mice via the portal vein, these cells expressed albumin until the sacrifice of the animals (17 days). The next steps will be to define conditions for transplantation of retrovirally transduced fetal primary and/or immortalized hepatocytes into young foetuses (60 days of gestation) and post-natally.

Prenatal diagnosis of sporadic Apert syndrome: a sequential diagnostic approach combining three-dimensional computed tomography and molecular biology.

Apert syndrome is characterized by coronal craniosynostosis, midfacial hypoplasia, symmetrical syndactyly of the hands and feet described as 'mitten-like' with varying degrees of mental retardation. It results from a mutation of the fibroblast growth factor-2 (FGFR2) gene. In the absence of a family history, prenatal diagnosis may be difficult based on sonography alone. We report a case in which the prenatal diagnosis of Apert syndrome was suspected by ultrasonography, established by three-dimensional computed tomography scan (3DTS) and confirmed by the detection of a mutation on amniotic cells. This underscores the usefulness of a sequential diagnostic approach combining 3DTS and molecular biology in cases in which sonography alone is not con- clusive.