RESUMO
The occurrence of rudimentary horn pregnancy is an extremely rare and potentially serious obstetric entity, threatening maternal and fetal outcome. The authors report five cases of rudimentary horn pregnancy, the difficulties in making a proper diagnosis and the therapeutic management of this pathological entity, stressing the importance of transvaginal ultrasound, of pelvic MRI and laparoscopy in the early diagnosis of this type of uterine malformation.
Assuntos
Laparoscopia/métodos , Gravidez Ectópica/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Útero/anormalidades , Adulto , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Gravidez , Gravidez Ectópica/patologia , Gravidez Ectópica/terapia , Estudos Retrospectivos , Útero/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVES: Survival Motor Neuron (SMN) protein levels may become key pharmacodynamic (PD) markers in spinal muscular atrophy (SMA) clinical trials. SMN protein in peripheral blood mononuclear cells (PBMCs) can be quantified for trials using an enzyme-linked immunosorbent assay (ELISA). We developed protocols to collect, process, store and analyze these samples in a standardized manner for SMA clinical studies, and to understand the impact of age and intraindividual variability over time on PBMC SMN signal. METHODS: Several variables affecting SMN protein signal were evaluated using an ELISA. Samples were from healthy adults, adult with respiratory infections, SMA patients, and adult SMA carriers. RESULTS: Delaying PBMCs processing by 45 min, 2 hr or 24 hr after collection or isolation allows sensitive detection of SMN levels and high cell viability (>90%). SMN levels from PBMCs isolated by EDTA tubes/Lymphoprep gradient are stable with processing delays and have greater signal compared to CPT-collected samples. SMN signal in healthy individuals varies up to 8x when collected at intervals up to 1 month. SMN signals from individuals with respiratory infections show 3-5x changes, driven largely by the CD14 fraction. SMN signal in PBMC frozen lysates are relatively stable for up to 6 months. Cross-sectional analysis of PBMCs from SMA patients and carriers suggest SMN protein levels decline with age. CONCLUSIONS: The sources of SMN signal variability in PBMCs need to be considered in the design and of SMA clinical trials, and interpreted in light of recent medical history. Improved normalization to DNA or PBMC subcellular fractions may mitigate signal variability and should be explored in SMA patients.
Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Proteínas do Complexo SMN/metabolismo , Adolescente , Adulto , Portador Sadio/sangue , Contagem de Células , Separação Celular , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Atrofia Muscular Espinal/sangue , Infecções Respiratórias/sangue , Adulto JovemRESUMO
The design and synthesis of the novel 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole 5 is described. This azepinoindole has excellent affinity for 5-HT(2C) (K(i) 4.8 nM) and modest selectivity over 5-HT(2A) ( approximately 4-fold). Several N- and C(11)-substituted analogues of 5 were prepared, as were a number of biaryl indoline derivatives. The anxiolytic potential for the azepinoindole template 5 is demonstrated by activity in a mouse shock-aggression assay.