A. Mignon

Selective repopulation of normal mouse liver by Fas/CD95-resistant hepatocytes

Hepatocyte transplantation might represent a potential therapeutic alternative to liver transplantation in the future; however, transplanted cells have a limited capacity to repopulate the liver, as they do not proliferate under normal conditions. Recently, studies in urokinase (uPA) transgenic mice and in fumarylacetoacetate hydrolase (FAH)-deficient mice have shown that the liver can be repopulated by genetically engineered hepatocytes harboring a selective advantage over resident hepatocytes. We have reported that transgenic mice expressing human Bcl-2 in their hepatocytes are protected from Fas/CD95-mediated liver apoptosis. We now show that Bcl-2 transplanted hepatocytes selectively repopulate the liver of mice treated with nonlethal doses of the anti-Fas antibody Jo2. FK 506 immunosuppressed mice were transplanted by splenic injection with Bcl-2 hepatocytes. The livers of female recipients were repopulated by male Bcl-2 transgenic hepatocytes, as much as 16%, after 8 to 12 administrations of Jo2. This only occurred after anti-Fas treatment, confirming that resistance to Fas-induced apoptosis constituted the selective advantage of these transplanted hepatocytes. Thus, we have demonstrated a method for increasing genetic reconstitution of the liver through selective repopulation with modified transgenic hepatocytes, which will allow optimization of cell and gene therapy in the liver.

Analgesic efficacy and adverse effects of epidural morphine compared to parenteral opioids after elective caesarean section: A systematic review

Background: The optimal effective dose of epidural morphine that provides postoperative analgesia after caesarean section with minimal side effects remains debated.

Careful cardiovascular screening and follow-up of women with Turner syndrome before and during pregnancy is necessary to prevent maternal mortality

OBJECTIVEnTo report the fatal outcome of a woman with Turner syndrome (TS) undergoing assisted reproductive technology (ART).nnnDESIGNnCase report.nnnSETTINGnReproductive medicine center.nnnPATIENT(S)nA 33-year-old woman with TS.nnnINTERVENTION(S)nScreening before oocyte donation and treatment of aortic dissection occurring at term pregnancy.nnnMAIN OUTCOME MEASURE(S)nEvaluation of cardiovascular risk.nnnRESULT(S)nAfter a normal cardiac screening, a woman with TS got pregnant as a result of oocyte donation. At 16 weeks of gestation, a bicuspid aortic valve was detected and associated with moderate aortic root dilation. Aortic dissection was diagnosed at 38 weeks of gestation, which required emergent cesarean delivery and aortic root replacement. Despite surgical treatment, early maternal death was recorded.nnnCONCLUSION(S)nCareful cardiac screening and close follow-up before and during pregnancy are necessary in patients with TS.

Conséquences fœtales des techniques d’anesthésie au cours du travail

Continuous electronic fetal heart rate (FHR) monitoring is part of routine care for laboring patients under either systemic or locoregional analgesia. Opioid systemic analgesia (mainly meperidine in early labor), yet less frequently used in our country, is associated with a decrease in FHR-variability and worse acid-base and neonatal status compared to epidural or combined spinal epidural analgesia. Although epidural analgesia may cause maternal hypotension and fever, longer second stage of labour and more instrumental vaginal deliveries, these potentially adverse factors appear to be outweighed by benefits on clinical and neonatal acid-base status when compared with maternal opioid systemic analgesia. The mechanisms by which epidural or spinal analgesia may affect fetal well-being include maternal hypotension and/or uterine hyperactivity. All these undesirable side effects which may induce severe intrapartum fetal distress must be adequately detected and treated with intrauterine resuscitation techniques, including correction of maternal hypotension and/or the use of tocolytics agents. Reinstallation of electronic fetal monitoring at arrival in the operating room before cesarean section for suspected fetal hypoxia may be helpful to choose better anesthetic technique and try to avoid general anesthesia associated with increased maternal morbidity and mortality.Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 37 - N° 1S - p. 46-55

Ventricular fibrillation during termination of pregnancy

In June, 2006, a 29-year-old woman underwent a termination of pregnancy at 35 weeks of gestation, because the fetus had been found to have porencephaly. She had had three previous pregnancies, of which two had proceeded to term; her medical history was otherwise unremarkable. The fetus was killed with sufentanil and lidocaine. Misoprostol was administered intravaginally to induce labour, and the membranes were artifi cially ruptured. 15 min later, the patient suddenly lost consciousness and began to gasp for breath. She entered ventricular fi brillation. She was immediately intubated and ventilated; cardiac massage was done; and she was given three DC shocks. The period between onset of cardiac arrest and the start of life support was estimated at around 3 min; life support was given for about 10 min. Immediate transthoracic echocardiography, using an obstetric ultrasound device, showed a massively dilated hypokinetic right ventricle, with fl oating echo-dense masses (fi gure). Blood test results indicated disseminated intravascular coagulation (platelet and fi brinogen concentrations very low at 20×109/L and 0·59 μmol/L respectively; activated partial thromboplastin time >120 s). Within 1 h of the onset of cardiac arrest, the fetus was delivered—with subsequent profuse vaginal bleeding. Manual exploration of the uterus, uterine massage, intravenous oxytocin, and uterine packing all failed to stem the bleeding, so a sulprostone infusion was started, and the patient was given several units of blood, which stabilised her condition. The combination of cardio vascular collapse, coagulopathy, and the echocardiographic fi ndings indicated that an amnioticfl uid embolism (AFE) was likely; a blood sample was immediately analysed by the pathologist, who observed amniotic and fetal cells after staining the sample with Wright’s stain and Nile blue stain. The patient was transferred to another hospital, where more intensive management was possible. She was given bilateral uterine embolisation, which caused the bleeding to cease. However, her haemodynamic stability deteriorated, despite increasing doses of epinephrine and dobutamine. Transoesophageal echo cardiography showed left ventricular failure (ejection fraction <15%). 8 h after cardiac arrest, extracorporeal life support (ECLS) was initiated, by use of a femoro-femoral bypass. The patient’s left ventricular function did not improve. She developed a fever and a raised white cell count that appeared to be caused not by an infection, but a systemic infl ammatory reaction. 12 days after cardiac arrest, the decision was made to give intravenous hydrocortisone (50 mg every 6 h). Left ventricular function began to recover within hours, and we were able to discontinue ECLS 20 days after cardiac arrest. The patient was extubated on day 26, and discharged on day 40. When last seen, in March, 2007, the patient was well, with no evidence of neurological damage; she had resumed work, and was preparing to run the Paris marathon. AFE is a rare complication of pregnancy, occurring in one in 20 000–50 000 deliveries. However, it is one of the leading causes of maternal mortality in developed countries; the proportion of patients surviving without neurological damage is only 15%. The presence of amniotic fl uid in the maternal bloodstream causes severe vasoconstriction and pulmonary hypertension. There follows a cascade of infl ammatory activation, similar to the systemic infl ammatory response caused by sepsis or burns. This process can cause multiple organ dysfunction, and typically depresses the myocardium. This scenario needs to be anticipated, so that alternative treatments—which can include ECLS—can be initiated or prepared. In this case, steroids appeared instrumental in reversing left ventricular dysfunction, perhaps because of their anti-infl ammatory activity. Had ventricular function not recovered, a heart transplant might have been necessary.

Le sulfate de magnésium en obstétrique : données actuelles

Resume Objectif Effectuer une revue objective des donnees disponibles concernant l’histoire, la pharmacologie, la physiologie, les effets secondaires et l’efficacite du sulfate de magnesium dans ses deux principales indications obstetricales, la tocolyse et la crise d’eclampsie. Donnees Une revue de la litterature a ete effectuee dans Medline de 1966 a avril 2003 en utilisant les mots cles suivants : magnesium sulfate , tocolytic , pre-eclampsia , eclampsia , et pregnancy . Les references bibliographiques des articles ont egalement ete analysees a la recherche de donnees additionnelles. Resultats Le sulfate de magnesium (MgSO4) est utilise en pratique obstetricale depuis des decennies pour prevenir la prematurite (effet tocolytique) et la survenue d’une crise d’eclampsie (effet neuroprotecteur). Plusieurs essais randomises et des meta-analyses ont maintenant demontre l’efficacite du sulfate de magnesium dans la prevention primaire et secondaire de la crise d’eclampsie. A l’inverse, le sulfate de magnesium n’est pas efficace comme tocolytique et son utilisation a forte posologie semble etre associee a un risque accru de mortalite perinatale. Conclusion Le sulfate de magnesium previent la survenue d’une crise d’eclampsie chez la femme pre-eclamptique. En revanche, son utilisation n’est pas recommandee a visee tocolytique.

Sudden coma after subclavian catheterization

Bilateral thalamic infarction is a very rare affection. We report here a case of bithalamic infarction during subclavian catheterization related to the accidental migration and complete occlusion of an arterial embolism to the Percherons artery. Percherons artery is an anatomical variation described in 1977, constituted by a solitary arterial trunk arising from one of the proximal segments of a posterior cerebral artery supplying the paramedian thalami and the rostral midbrain bilaterally. We review here the clinical presentation and discuss the aetiologies of such a cerebral infarction.

Infections pelviennes graves de la femme

Les infections pelviennes graves de la femme constituent la forme la plus severe d’une maladie appelee « maladie inflammatoire du pelvis » ou encore « pelvic inflammatory disease (PID) » par les Anglo-Saxons (1). Cette affection, que nous connaissons plus generalement sous le terme generique d’infection genitale haute, fait reference a toute infection de l’uterus, des trompes ou des structures pelviennes adjacentes en dehors d’un contexte chirurgical ou de la grossesse. Elle regroupe l’endocervicite, l’endometrite et la salpingite. L’endocervicite correspond a l’infection du canal cervical au-dela de l’orifice externe, l’endometrite a l’infection localisee de l’uterus, et la salpingite a l’atteinte utero-annexielle. Malgre ces distinctions nosologiques, l’ensemble de ces pathologies represente une seule entite, avec une prise en charge tres similaire dans le cadre des maladies sexuellement transmissibles (MST). Il s’agit d’une affection frequente (1 million de cas par an aux Etats-Unis) qui genere des complications (douleurs chroniques, grossesse extra-uterine [GEU], infertilite) et des couts tres importants (1 milliard

Embolie amniotique. Succès de mise en place d’une assistance cardio-respiratoire (ECLS)

par an aux memes Etats-Unis) (2).

Comparaison historique de deux types de prises en charge de placenta accreta : radicale versus conservatrice

Mme L. 29 ans ne presente aucun antecedent medical ou chirurgical particulier en dehors de deux accouchements par voie basse en 2002 et 2004. Au stade de 32 semaines d’amenorrhee, une interruption medicale de grossesse est demandee pour AVC ischemique fœtal avec hemiplegie sequellaire. Un malaise brutal (mouvements tonico-cloniques) survient 4 heures environ apres la rupture artificielle des membranes, avec a l’examen une patiente inconsciente, une tachycardie sinusale, une hypotension (TA imprenable), une cyanose du territoire cave superieur, une turgescence jugulaire. Un episode de bradycardie sinusale ( 2 100 %. Une echographie cardiaque est alors realisee. Les hypotheses diagnostiques envisagees sont un accident des anesthesiques locaux, une embolie amniotique ou une embolie cruorique necessitant une thrombolyse en urgence. Le bilan retrouve une acidose metabolique associe a une CIVD. Une hemorragie de la delivrance avec persistance d’un saignement uterin modere mais continu necessite un transfert a l’HEGP dans le pole cardio-vasculaire pour une embolisation bilaterale des arteres uterines et mise en place d’un filtre cave. Au decours de ce geste, la fonction ventriculaire gauche se degrade (FE Morbi/mortalite de l’embolie amniotique Les derniers chiffres montrent un taux de mortalite entre 26 a 37 % ainsi que 13 % sequelles neurologiques. Conclusion Une reanimation immediate est indispensable avec traitements des detresses vitales maternelle, du choc hypovolemique, de la CIVD, prise en charge obstetricale medicale, chirurgicale ou radiologique pour l’extraction fœtale et le traitement de l’hemorragie de la delivrance, mais surtout mise en place tres rapide au stade du choc cardiogenique d’une ECLS.