Differential Expression of Vegfr-2 and Its Soluble Form in Preeclampsia

Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably, soluble sVEGFR-1 (also known as sFlt-1) and soluble endoglin (sEng), as well as to decreased PlGF. Recently, soluble VEGF type 2 receptor (sVEGFR-2) has emerged as a crucial regulator of lymphangiogenesis. To date, however, there is a paucity of information on the changes of VEGFR-2 that occur during the clinical onset of PE. Therefore, the aim of our study was to characterize the plasma levels of VEGFR-2 in PE patients and to perform VEGFR-2 immunolocalization in placenta.By ELISA, we observed that the VEGFR-2 plasma levels were reduced during PE compared with normal gestational age matched pregnancies, whereas the VEGFR-1 and Eng plasma levels were increased. The dramatic drop in the VEGFR-1 levels shortly after delivery confirmed its placental origin. In contrast, the plasma levels of Eng and VEGFR-2 decreased only moderately during the early postpartum period. An RT-PCR analysis showed that the relative levels of VEGFR-1, sVEGFR-1 and Eng mRNA were increased in the placentas of women with severe PE. The relative levels of VEGFR-2 mRNA as well as expressing cells, were similar in both groups. We also made the novel finding that a recently described alternatively spliced VEGFR-2 mRNA variant was present at lower relative levels in the preeclamptic placentas.Our results indicate that the plasma levels of anti-angiogenic factors, particularly VEGFR-1 and VEGFR-2, behave in different ways after delivery. The rapid decrease in plasma VEGFR-1 levels appears to be a consequence of the delivery of the placenta. The persistent circulating levels of VEGFR-2 suggest a maternal endothelial origin of this peptide. The decreased VEGFR-2 plasma levels in preeclamptic women may serve as a marker of endothelial dysfunction

Risk factors for peripartum hysterectomy among women with postpartum haemorrhage: analysis of data from the WOMAN trial.

BACKGROUND: Peripartum hysterectomy can cause significant morbidity and mortality. Most studies of peripartum hysterectomy are from high income countries. This cohort study examined risk factors for peripartum hysterectomy using data from Africa, Asia, Europe and the Americas. METHODS: We used data from the World Maternal Antifibrinolytic (WOMAN) trial carried out in 193 hospitals in 21 countries. Peripartum hysterectomy was defined as hysterectomy within 6 weeks of delivery as a complication of postpartum haemorrhage. Univariable and multivariable random effects logistic regression models were used to analyse risk factors. A hierarchical conceptual framework guided our multivariable analysis. RESULTS: Five percent of women had a hysterectomy (1020/20,017). Haemorrhage from placenta praevia/accreta carried a higher risk of hysterectomy (17%) than surgical trauma/tears (5%) and uterine atony (3%). The adjusted odds ratio (AOR) for hysterectomy in women with placenta praevia/accreta was 3.2 (95% CI: 2.7-3.8), compared to uterine atony. The risk of hysterectomy increased with maternal age. Caesarean section was associated with fourfold higher odds of hysterectomy than vaginal delivery (AOR 4.3, 95% CI: 3.6-5.0). Mothers in Asia had a higher hysterectomy incidence (7%) than mothers in Africa (5%) (AOR: 1.2, 95% CI: 0.9-1.7). CONCLUSIONS: Placenta praevia/accreta is associated with a higher risk of peripartum hysterectomy. Other risk factors for hysterectomy are advanced maternal age, caesarean section and giving birth in Asia

Leishmaniose viscérale chronique au cours d'une chimiothérapie pour ostéosarcome métastatique

Chronic visceral leishmaniasis during chemotherapy for metastatic osteosarcoma. Leishmaniasis refers to a spectrum of diseases caused by Leishmania. Clinically, three types of leishmaniasis can be distinguished : the cutaneous, mucous and visceral leishmaniasis, the latter being caused by Leishmania donovani. Case report. - An 11-year-old Thai, living in Belgium for 6 years, had surgery for a vertebral osteosarcoma with pulmonary metastases, followed by polychemotherapy, then pulmonary metastasectomy. During a post-chemotherapy bone marrow aplasia, febrile episode with a general condition impairment was noted and first treated by broad-spectrum antibiotherapy, then by amphotericin B, in the absence of any accurate etiology. The outcome first was favourable. Nevertheless, 7 months later, the visceral leishmaniasis diagnosis was made because of the recurrence of the same symptoms. Classical treatments by antimony derivatives (Glucantim®), then liposomal amphotericin (Ambisome ®) proved to he inefficient. A liposomal amphotericin-gamma interferon association suppressed the symptoms without eradicating the parasite. The patient was given a maintenance therapy based on liposomal amphot ricin. Conclusion. - The stubborn and recurring nature this chronic visceral leismaniosis can be due to the immune deficit inherent in the polychemotherapy performed in order to treat the metastatic osteosareoma which currently is in first full remission.On observe trois types de leishmanioses : la leishmaniose cutanée, la leishmaniose muqueuse et la leishmaniose viscérale, cette dernière étant provoquée par Leishmania donovani. Observation. - Un enfant de 11 ans, d'origine thaïlandaise, résidant en Belgique depuis 6 ans, est opéré d'un ostéosarcome vertébral, métastasé au niveau pulmonaire, ce qui conduit à une polychimiothérapie suivie d'une métastasectomie pulmonaire. Un épisode d'hyperthermie, sans cause précise, avec altération de l'état général lors d'une aplasie médullaire postchimiothérapique est traité par une antibiothéapie à large spectre puis par amphotéricine b. L'évolution est d'abord favorable puis, 7 mois plus tard un diagnostic de leishmaniose viscérale est posé à la suite de la réapparition des mêmes symptômes. Les traitements classiques par dérivés de l'antimoine (Glucantime®), puis par amphotéricine liposomale (Ambisome ®) se montrent inefficaces, Une association amphotéricine liposomale et interféron gamma amende les symptômes sans éradiquer le parasite de I'organisme. Face cette leishmaniose viscérale chronique, le patient reçoit un traitement de maintenance par amphotéricine liposomale. Conclusion. -Le caractère réfractaire et récidivant de cette leishmaniose viscérale chronique pourrait être secondaire au déficit immunitaire inhérent à la polychimiotédrapie reçue en raison d'un ostéosarcome métastatique, actuellement en première rémission complèt

PHARMA -CLINICS : Comment je traite ...L'anémie falciforme chez l'enfant.

peer reviewe

Cutaneous involvement in children with acute lymphoblastic leukemia or lymphoblastic lymphoma

Objective. Skin involvement in children with acute monocytic leukemia or CD30-positive anaplastic large-cell lymphoma is well-known. In contrast, very little is known about the malignant cutaneous infiltrates in children with acute lymphoblatic leukemia (ALL) or lymphoblastic lymphoma (LBL). This study was designed to determine the frequency of these specific lesions in childhood ALL or LBL and the characteristics of such patients. Design. We studied the clinical and biological findings of children with cutaneous involvement at initial diagnosis of ALL or LBL enrolled between August 1989 and March 1995 in the multicentric trial 58881 of the Children's Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC). Results. Among the 1359 children enrolled in the multicenter trial EORTC 58881, 24 presented with skin involvement at diagnosis. ALL was diagnosed in 15 patients and LBL in 9. In 15 cases, skin lesions were observed within a median time of 6 weeks (range, a few days to 8 months) before the diagnosis of the hematologic disease. Twenty-one children had at least one skin lesion located on the head. Diffuse cutaneous lesions were observed in 7 infants with high-risk ALL. Seventeen of the 24 children remain in the first complete remission (median follow-up of 3 years; range 2 months to 5 years) and 3 are in the second remission with a follow-up of 14 to 24 months. Conclusion. The present study demonstrates that cutaneous involvement can be an early manifestation of ALL or LBL. Cutaneous leukemic infiltrates can be observed in children with standard risk as well as in highrisk ALL. Cutaneous involvement in children with LBL is mainly associated with a B-cell precursor immunophenotype of the lymphomatous cells. The most frequent location of skin lesions in children with ALL or LBL is on the head. Further studies are needed to evaluate the prognosis of children with such involvement at diagnosis