Les complications pulmonaires après allogreffe de cellules souches hématopïétiques

Les complications pulmonaires après allogreffe de cellules souches hématopoïétiques (CSHP) sont fréquentes dont la réaction du greffon contre l hôte (GVH) pulmonaire chronique qui contribue grandement à la mortalité et à la morbidité en post-greffe. Le syndrome de bronchiolite oblitérante (BOS) est la forme la plus fréquente et sévère. Notre étude monocentrique prospective avait pour but de déterminer les complications pulmonaires survenant après allogreffe de CSHP sur 67 patients greffés à Angers avec une médiane de suivie de 10,5 mois. Elle devait préciser l incidence, les facteurs de risque et le pronostic des patients atteints de BOS et évaluer la faisabilité d un suivi systématique de la fonction respiratoire en post-allogreffe. 46,3% des patients ont présenté une complication pulmonaire majoritairement de type infectieuse. La prévalence des BOS était de 6% chez les patients allogreffés de CSHP et de 21% chez les patients ayant présenté une GVH chronique. Aucun facteur de risque n était significatif en ce qui concerne les BOS. Cependant pour les patients diagnostiqués à risque de développer un BOS définis selon JW. Chien en 2003, les facteurs de risque significatifs étaient l utilisation d un conditionnement myéloatténué et la présence d une GVH chronique extra-pulmonaire. Le taux de mortalité des BOS était de 50% à 20 mois post-greffe. Peu de patients ont pu réaliser leurs EFR de façon systématique durant leur suivi. Si un suivi systématique et rapproché des EFR semble souhaitable afin de dépister précocement le BOS, il semble difficile du fait de la fragilité des patients et de la fréquence des complications intercurrentes.Pulmonary complications after allogeneic hematopoietic stem cell transplantation (aHCT) are common. Bronchiolitis obliterans syndrome (BOS) is the most common and severe manifestation of chronic graft versus host disease (GVHD) lung injury and increases morbidity and mortality. The aim of our prospective study was to describe aHCT pulmonary complications, especially BOS. It included 67 patients transplanted in Angers hospital with a median follow-up of 10,5 months. It aimed to describe incidence, risk factors and prognostic of patients with BOS and to evaluate a systematic lung function follow-up after aHCT. 46,3% of patients had pulmonary complications, essentially infectious complications. The prevalence of BOS for all patients receiving aHCT was 6% and 21% among patients who developed chronic GVHD. We did not identify predictive factors of BOS in our population. However in patients susceptible to develop BOS with an airflow obstruction, there was a significantly association with reducted-intensity conditioning and with GVHD. Mortality rate of BOS was 50% at 20 months. Systematic spirometric following was not possible for many patients. Althrough if systematic lung function follow-up seems advisable for early detection of BOS, it appears to be difficult because of the fragile state of the patients.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

The developing female genital tract: from genetics to epigenetics.

International audienceThe mammalian female reproductive tract develops from the Mullerian ducts which differentiate, in a cranial to caudal direction, into oviducts, uterine horns, cervix and the anterior vagina. The developmental processes taking place during this organogenesis are notably under the control of steroid hormones, such as members of the Wnt and Hox families, which regulate key developmental genes. At later stages, steroid hormones also participate in the development of the female genital tract. Chemical compounds homologous to steroids can thus act as agonists or antagonists in fetuses exposed to them. These so-called endocrine disruptors are nowadays found in increasing amounts in the environment and may therefore have a particular impact on such developing organs. Epidemiological studies have revealed that endocrine disruptors have had drastic effects on female health and fertility during the last decades. Furthermore, these adverse effects might be transmitted to subsequent generations through epigenetic modifications. Given the potential hazard of inherited epigenetic marks altering reproduction and/or human health, such molecular mechanisms must be urgently investigated. This review aims to summarize the cellular and molecular mechanisms involved in female genital tract development, to highlight key genes involved in this process and to present epigenetic mechanisms triggered by endocrine disruptors and their consequences in regard to female reproductive tract development

Epilepsy in young Tsc1+/− mice exhibits age-dependent expression that mimics that of human tuberous sclerosis complex

International audienceObjective - To describe the epileptic phenotype of Tsc1(+/-) mice pups in comparison with age-related seizures in human tuberous sclerosis complex (TSC). Methods - Tsc1(+/-) and control mice underwent intracranial electroencephalography (EEG) recording at postnatal ages (P)8 to P33, with linear silicon probe implanted in the somatosensory cortex of one or both hemispheres for 8-24 h. Ictal events were classified visually by independent analyzers; distinct EEG patterns were related to age and analyzed to quantify field potential characteristics and signal dynamics between hemispheres. We collected retrospectively 20 infants with prenatally diagnosed TSC and EEG before seizure onset, and analyzed the electroclinical course of epilepsy, taking into account a first-line treatment by vigabatrin. Results - Spontaneous seizures were disclosed in 55% of Tsc1(+/-) mice at P9-18. Three ictal patterns were identified: from P9 to P12 "spike clusters" consisted of recurring large spikes without clinical correlate; "spasm-like" discharges dominated from P13 to P16 consisting of high amplitude large field potential superimposed with or followed by fast activity repeated every 2-10 s for at least 20 s, accompanied by rhythmic limb contractions; from P14 to P18 a "tonic-clonic like" pattern comprised rhythmic spikes of increasing amplitude with tonic-clonic movements. Early onset "spike clusters" were mainly unilateral, whereas "spasm-like" and "tonic-clonic like" patterns were bilateral. Interhemispheric propagation was significantly faster for "tonic-clonic like" than for "spasm-like" events. In infants diagnosed prenatally with TSC, clusters of sharp waves or spikes preceded the first seizure, and vigabatrin prevented the development of seizures. Patients treated after seizure onset developed spasms or focal seizures that were pharmacoresistant in 66.7% of cases. Significance - Tsc1(+/-) mice pups exhibit an age-dependent seizure pattern sequence mimicking early human TSC epilepsy features. Spike clusters before seizure onset in TSC should be considered as a first stage of epilepsy reinforcing the concept of preventive antiepileptic therapy