Mesure échographique de l'épaisseur du segment inférieur et ruptures utérines en cas d'utérus unicicatriciel

Les ruptures utérines en cas d'accouchement voie basse après césarienne surviennent dans environ 1% des cas. Ce sont des complications graves pour la mère et l'enfant. La mesure échographique de l'épaisseur du segment inférieur a pour but d'identifier les patientes avec un segment inférieur <= 3,5mm qui sont plus à risque de rupture utérine afin de les orienter vers le mode d'accouchement le plus approprié. Ce travail a pour but d'évaluer la réalisation de cette mesure en pratique courante. Sur 1145 dossiers, 10 ruptures ont été identifiées, aucune n'avait une épaisseur du segment inférieur <= 3,5mm. La valeur prédictive négative de ce seuil est excellente (0,98) et conforme aux données de la littérature. Cependant, parmi les patientes avec un segment inférieur en dessous de 3,5mm, il n'y a pas eu de rupture utérine quelque soit la voie d'accouchement. Après analyse statistique, il n'y a pas de meilleur seuil pour notre population.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Cancers de l' endomètre sous tamoxifène après un cancer du sein, de 1998 à 2002, dans le département de Loire-Atlantique

Le risque de cancer de l' endomètre sous tamoxifène après un cancer du sein existe mais il reste faible (RR=2 à 3). Il faut tenir compte de la durée du traitement ainsi que de l' association avec d' autres facteurs de risque (oestrogénothérapie seule, obésité) pour évaluer le risque de cancer de l' endomètre d' une patiente prenant du tamoxifène. Si la majorité des tumeurs sont des adénocarcinomes endométrioïdes bien différenciés découverts à un stade précoce, certains cancers sont particulièrement agressifs par leur type histologique (carcinome à cellules claires, carcinome papillaire séreux, sarcome), leur faible différenciation ou/et leur caractère invasif, entraînant une diminution de la survie spécifique dans certaines études. L' augmentation du risque de cancer de l' endomètre sous tamoxifène est largement contrebalancée par le bénéfice attendu de ce médicament. Cependant, les anti-aromatases et le raloxifène, qui n' ont pas d effet sur l endomètre, pourraient supplanter le tamoxifène dans le traitement adjuvant du cancer du sein.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Complex Management of Nephrotic Syndrome and Kidney Failure during Pregnancy in a Type 1 Diabetes Patient: A Challenging Case

International audiencePregnancy with chronic kidney disease is challenging, and patients with diabetic nephropathy are at particular risk of a rapid kidney function decline during pregnancy. While indications for the management of pregnant patients with initial diabetic nephropathy are widely available in the literature, data on patients with severe nephrotic syndrome and kidney function impairment are lacking, and the decision on whether and when dialysis should be initiated is not univocal. We report a type 1 diabetes patient who started pregnancy with a severe nephrotic syndrome and shifted from CKD stage 3b to stage 5 during pregnancy. The management was complicated by a fetal heart malformation and by poorly controlled diabetes. The evidence for and against starting dialysis was carefully evaluated, and the choice of strict nephrological and obstetrical monitoring, nutritional management, and diuretic treatment made it possible to avoid dialysis in pregnancy, after ruling out pre-eclampsia. This experience enables examination of some open issues and contributes to the discussion of when to start dialysis in pregnancy

Effectiveness of nitrous oxide in external cephalic version on success rate: a randomized controlled trial

International audienc

Complex Management of Nephrotic Syndrome and Kidney Failure during Pregnancy in a Type 1 Diabetes Patient: A Challenging Case

International audiencePregnancy with chronic kidney disease is challenging, and patients with diabetic nephropathy are at particular risk of a rapid kidney function decline during pregnancy. While indications for the management of pregnant patients with initial diabetic nephropathy are widely available in the literature, data on patients with severe nephrotic syndrome and kidney function impairment are lacking, and the decision on whether and when dialysis should be initiated is not univocal. We report a type 1 diabetes patient who started pregnancy with a severe nephrotic syndrome and shifted from CKD stage 3b to stage 5 during pregnancy. The management was complicated by a fetal heart malformation and by poorly controlled diabetes. The evidence for and against starting dialysis was carefully evaluated, and the choice of strict nephrological and obstetrical monitoring, nutritional management, and diuretic treatment made it possible to avoid dialysis in pregnancy, after ruling out pre-eclampsia. This experience enables examination of some open issues and contributes to the discussion of when to start dialysis in pregnancy

Fetal Fibroblasts and Keratinocytes with Immunosuppressive Properties for Allogeneic Cell-Based Wound Therapy

<div><p>Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with <i>in vitro</i> scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO) activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the <i>in vitro</i> scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors.</p></div

Immunogenicity and Immunosuppressive activity of fetal cells.

<p><b>A,</b> MHC class I and class II expression in fetal cells. Flow cytometry analysis of MHC class I and class II expression in fetal fibroblasts and kerationcytes treated or not with 1 µg/ml IFN-γ for 48 hours. Full histograms represent test samples, solid lines represent isotypic controls. Percentage of positive cells and mean fluorescence intensity values (MFI) are indicated. Cytograms are typical of two independent experiments. <b>B,</b> Proliferation of allogeneic PBMC in co-culture with fetal fibroblasts, keratinocytes or both cell types in co-culture. PBMC were initially plated with various fetal cell numbers corresponding to four different ratios between fetal cells and PMBC, 1∶4, 1∶20, 1∶100 and 1∶200. PBMC were collected from the co-cultures after 5 days and treated with ³H-thymidine for 16 hours before radioactive counting. Data represent the means ± SD (n = 3) of ³H-thymidine incorporation by proliferative PBMC. Asterisks denote significant differences in PBMC proliferation compared to the positive control (column 2) (*, p<0.05; **, p<0.01; ***, p<0.001). Data are representative of three independent experiments performed with PBMC obtained from different healthy donors.</p

Scratch closure is faster in fetal fibroblast and keratinocyte co-cultures than in fibroblast or keratinocyte mono-cultures.

<p><b>A</b>, Representative images of the progression of the scratch closure at T0, 5 h and 20 h for keratinocytes (upper panel), fibroblasts (middle panel) and both in co-culture (lower panel). <b>B</b>, The extent of the scratch closure in scratch assays performed on fetal fibroblasts, keratinocytes or both in co-culture at 5 h and 20 h. Data shown are the means ± SD (n = 4). Asterisks denote significant differences in the extent of the scratch closure (*, p<0.05; **, p<0.01).</p

Characterization of the fetal fibroblasts and keratinocytes manufactured of the clinical batches.

<p><b>A</b>, Morphological and molecular characterization. Left panel, microphotography of the fetal fibroblasts and keratinocytes. Middle panel, immunofluorescence of cultured fetal fibroblasts and kerationcytes from the clinical batches, stained for nuclei (blue), prolyl-4-hydroxylase (green) and keratin 14 (red). Right panel, cytometry histograms showing the percentage of prolyl-4-hydroxylase positive cells and the percentage of keratin14 positive cells in the fetal fibroblasts and keratinocytes, respectively. Full histograms represent test samples, solid lines represent isotypic controls. <b>B</b>, Integrin expression profiles. Cytometry histograms showing β1-, α2- and α3-integrin expression in fetal fibroblasts (upper panel) and keratinocytes (lower panel). Cytograms are typical of at least three independent experiments.</p

Multiplex cytokine analysis of cell culture supernatants from fetal and adult fibroblasts and keratinocytes mono-cultures or fibroblasts and keratinocytes co-cultures.

<p>Supernatants from fibroblast and keratinocyte mono-cultures or both cell types in co-culture (ratio 1∶1) were collected to detect soluble HGF, GM-CSF, IL-1α, VEGF-A and IL-8 by multiplex immunoassay (see materials and methods). For adult skin cells, values are the means of three samples (see table 1). Fib., fibroblasts mono-culture; Ker., keratinocytes mono-culture; Fib./Ker. (1∶1), fibroblasts and keratinocytes co-culture at the ratio 1∶1.</p