Anne Wernet

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.

Intérêt de l’instillation pariétale unique de ropivacaïne dans la prévention des douleurs après césarienne

OBJECTIVE To assess the efficiency of single-shot ropivacaine wound infiltration during cesarean section for postoperative pain relief, using a prospective, randomized, double-blinded study. PATIENTS AND METHODS One hundred consecutive patients with planned cesarean section were enrolled between September 2007 and May 2008 and randomized into two groups: single-shot wound infiltration of 20mL of ropivacaine 7.5mg/mL (Group R; n=56) or single-shot wound infiltration of 20mL of saline solution (group T; n=44). The primary goal of this study was the double-blinded evaluation of the postoperative pain after coughing and leg raise using the 100-mm visual analog scales (VAS) during the first 48 postoperative hours after cesarean delivery. The secondary goals were the occurrence of nausea and vomiting and the morphine consumption. RESULTS Numerical pain rating scale for pain evaluation was significantly lower (P<0.05) in the ropivacaine group than in the control group at M0, M20, M40, M60, H2 and H4. But, at H8, H12 and H24, no significant difference for VAS was noted between the two groups. The occurrence of nausea and vomiting and the total morphine consumption were not significantly different between the two groups during the first 48 postoperative hours. DISCUSSION AND CONCLUSION Single-shot ropivacaine wound infiltration during planned cesarean section is a simple and safe procedure that provides effective reduction of post-partum pain within the first 4hours.

Malaria in pregnant woman masquerading as HELLP syndrome.

Malaria may be complicated by development of thrombocytopenia, elevated liver enzymes, and/or hemolysis, which may be difficult to distinguish from HELLP (hemolytic anemia; elevated liver enzymes; low platelet count) syndrome in a pregnant patient. A 33-year-old woman developed a HELLP-like syndrome and persistent fever postpartum without symptoms of preeclampsia. A malaria blood smear was performed and was positive for Plasmodium falciparum. The patient was immediately treated with quinine. The follow-up was uneventful with total disappearance of fever and prompt resolution of biochemical signs of HELLP-like syndrome 3 days later. Malaria in a pregnant woman can masquerade as HELLP syndrome. The wide overlap in symptoms (headache, malaise, digestive symptoms) does not suggest that symptoms would be effective in differentiating malaria and preeclampsia. A recent travel in endemic area, associated with malaria blood smear and clinic examination, should be the key of the differential diagnosis.

Use of insulin-like growth factor binding protein-1 for retrospective diagnosis of amniotic fluid embolism in first trimester.

A 27-year-old woman, gravida 2 para 1, was admitted for dilatation and curettage (D&C) for voluntary interruptions of pregnancy at 13 weeks of gestation. The patient had no significant personal history, with a normal previous pregnancy. She strongly desired general anesthesia. Pre-anesthesia fasting was of 6 h; 400 lg of misoprostol intravaginally and 400 mg of cimetidine orally had been administrated 4 h before surgery. General anesthesia with rapid sequence induction for tracheal intubation and controlled mechanical ventilation was decided, because of patient’s obesity (BMI = 37 kg/m), using 3.5 mg/kg of propofol, 1.5 mg/kg of succinylcholine, and sevoflurane 1.9 % in oxygen. D&C was realized without any complication. But, 5 min after termination of D&C, the patient presented sudden unexpected uncoordinated movements of upper and lower limbs, severe hypotension with low systolic blood pressure (43 mmHg), tachycardia (120 bpm), oxygen saturation decreasing to 92 % and wheezes were auscultated suggesting a component of bronchospasm. There were no sign of external hemorrhage; electrocardiogram scope showed ST-elevation of 2 mm, and capillary hemoglobin dosage was of 12.3 g/dL, identical to preoperative hemoglobin level. Iterative ephedrine boluses were administrated (total doses: 12 mg). All symptoms resolved within 5 min, and she was discharged to the recovery room after tracheal extubation. Post-operative electrocardiogram, troponin I (\10 lg/L; normal range \13.5 lg/L) and coagulation tests were normal. Post-operative course was uneventful. Serum tryptase and histamine concentrations measured at 30 and 90 min after shock were negative. Serum alpha-fetoprotein (AFP; 294 vs. 31.4 ng/mL before shock; normal range \10 ng/mL) and insulin-like growth factor binding protein-1 (IGFBP-1; 2,542 vs. 72 lg/L before shock) levels were significantly higher 90 min after onset of shock compared to levels in maternal serum, initially sampled for platelets and coagulation studies the day before the shock. Anaphylactoid shock, acute coronary syndrome and acute pulmonary embolism (rapid resolution of symptoms with normal examination) were ruled out and amniotic fluid embolism was our final diagnosis. Amniotic fluid embolism is rare (1/8,000 to 1/80,000 pregnancies), unpredictable, often fatal, and usually occurs during or soon after labor, rarely induced by uterine surgical manipulations or surgical trauma during pregnancy, even following curettage procedure in early pregnancy [1–4]. The diagnosis remains largely a clinical one, essentially a diagnosis of exclusion or an autopsy-proven analysis, because there is no specific routine diagnostic test to confirm an amniotic fluid embolism. In our case, D&C seems to be the dramatic triggering event, even if authors documented an increasing risk of death from amniotic fluid embolism during voluntary interruptions of pregnancy after 12 weeks, and a decreasing risk of abortion-related amniotic fluid embolism using D&C at about 13 weeks [5, 6]. A. Wernet Department of Anesthesia and Intensive Care, Hôpital Beaujon, AP-HP, Université Paris 7, Clichy, France