RESUMO
Perlecan is a large heparan sulfate (HS) proteoglycan present in all basement membranes and in some other tissues such as cartilage, and is implicated in cell growth and differentiation. Mice lacking the perlecan gene (Hspg2) have a severe chondrodysplasia with dyssegmental ossification of the spine and show radiographic, clinical and chondro-osseous morphology similar to a lethal autosomal recessive disorder in humans termed dyssegmental dysplasia, Silverman-Handmaker type (DDSH; MIM 224410). Here we report a homozygous, 89-bp duplication in exon 34 of HSPG2 in a pair of siblings with DDSH born to consanguineous parents, and heterozygous point mutations in the 5' donor site of intron 52 and in the middle of exon 73 in a third, unrelated patient, causing skipping of the entire exons 52 and 73 of the HSPG2 transcript, respectively. These mutations are predicted to cause a frameshift, resulting in a truncated protein core. The cartilage matrix from these patients stained poorly with antibody specific for perlecan, but there was staining of intracellular inclusion bodies. Biochemically, truncated perlecan was not secreted by the patient fibroblasts, but was degraded to smaller fragments within the cells. Thus, DDSH is caused by a functional null mutation of HSPG2. Our findings demonstrate the critical role of perlecan in cartilage development.
Assuntos
Proteoglicanas de Heparan Sulfato/genética , Mutação , Osteocondrodisplasias/genética , Animais , Proteoglicanas de Heparan Sulfato/fisiologia , Humanos , Recém-Nascido , Masculino , Camundongos , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: In vitro maturation (IVM) has some advantages over conventional in vitro fertilization (IVF), particularly in polycystic ovary syndrome (PCOS) where the risk of ovarian hyperstimulation is high. We studied the live birth rate in a large series of PCOS women undergoing human chorionic gonadotropin (hCG)-priming IVM. METHODS: This retrospective study included women with PCOS aged 18-42 years undergoing IVM with hCG priming. We reported live birth rate after the first embryo transfer and cumulative live birth rate from embryos obtained in the IVM cycle. We also performed logistic regression to assess which factors predicted number of oocytes and live birth. RESULTS: We included 921 women (age 28.9±3.5 years, body mass index 21.8±3.1 kg/m2, infertility duration 3.7±2.6 years, 81% primary infertility, 88% first IVF attempt, 94% ovulation induction failure). Live birth rate after the first embryo transfer was 31.7%, with a cumulative live birth rate from the cycle of 33.7%. High anti-Müllerian hormone levels predicted a high number of oocytes and a high oocyte maturation rate while the opposite was the case when luteinizing hormone levels were high. CONCLUSIONS: In women with PCOS, hCG priming IVM was feasible and resulted in acceptable live birth rates.
Assuntos
Gonadotropina Coriônica/uso terapêutico , Transferência Embrionária , Técnicas de Maturação in Vitro de Oócitos , Nascido Vivo/epidemiologia , Adolescente , Adulto , Coeficiente de Natalidade , Feminino , Humanos , Infertilidade Feminina , Síndrome do Ovário Policístico , Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
RATIONALE AND OBJECTIVES: To improve the accuracy of magnetic resonance imaging (MRI) in evaluating the response of osteosarcomas to preoperative chemotherapy, the authors developed a technique of mapping tumor necrosis and viability by quantitating slope values of gadolinium-DTPA (Gd-DTPA) uptake on dynamic fast low-angle shot (FLASH) images. METHODS: Dynamic contrast-enhanced FLASH imaging of a single representative plane was performed on six osteosarcomas. Tumors were mapped by dividing resultant images into contiguous regions of interest and deriving slopes representing percentage increase in signal intensity (SI) per minute over the baseline for each region. The results were compared with estimations of viable tumor volume on subtracted Gd-DTPA-enhanced T1-weighted images and histologic maps of necrotic and viable tumor. RESULTS: Dynamic FLASH estimations of percent tumor necrosis using a critical slope value of 45% per minute correctly predicted histologic response to chemotherapy in all six patients. Comparison of dynamic FLASH and histologic maps showed a high degree of correlation. Static enhanced T1-weighted images overestimated the amount of residual viable tumor. CONCLUSIONS: Dynamic FLASH Gd-DTPA-enhanced mapping is a potentially useful noninvasive method of quantitating tumor response to chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/diagnóstico , Meios de Contraste , Gadolínio , Imageamento por Ressonância Magnética/métodos , Compostos Organometálicos , Osteossarcoma/diagnóstico , Ácido Pentético , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Criança , Doxorrubicina/administração & dosagem , Feminino , Gadolínio DTPA , Humanos , Ifosfamida/administração & dosagem , Imageamento por Ressonância Magnética/instrumentação , Masculino , Metotrexato/administração & dosagem , Necrose , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Cuidados Pré-OperatóriosRESUMO
The fitting characteristics of 1-day Acuvue disposable soft contact lenses (SCLs) [base curve (BC) 9.0 mm, diameter 14.2 mm] and 14-day Acuvue disposable SCLa (BC 8.8 mm, diameter 14.0 mm) were evaluated and compared with respect to lens centration and post-blink movement in primary gaze and in upgaze. In this double-blind study 25 successful daily wearers of either the 1-day lens or the 14-day lens with the same parameters were randomly fit with three 1-day lenses and three 14-day lenses for a total of 6 lenses per eye. The lene fit was evaluated 5 min after insertion. Lens centration was assessed by measuring temporal, nasal, superior and inferior limbal coverage, and then comparing the net horizontal centration (temporal minus nasal coverage) and the net vertical centration (superior minus inferior coverage) of the 1-day and 14-day lenses. There was no significant difference between the two lenses in terms of temporal, superior, and inferior limbal coverage (p > 0.05). However, the 1-day lens showed statistically more nasal coverage (p < 0.05). No statistically significant difference in movement or in horizontal and vertical differences in centration were found (p > 0.05). Although our findings indicate a subtle statistical difference in fitting characteristics, clinically the two lenses should provide similar fits.
Assuntos
Lentes de Contato Hidrofílicas , Equipamentos Descartáveis , Erros de Refração/terapia , Adulto , Análise de Variância , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ajuste de Prótese , Erros de Refração/fisiopatologia , Acuidade VisualRESUMO
Magnetic resonance imaging (MRI) is a sensitive method for the diagnosis of bone marrow abnormalities, but its usefulness in detecting active disseminated cancer in this tissue in treated patients has not been determined. We therefore examined 14 children who had been treated for disseminated bone marrow involvement by neuroblastoma (n = 6), lymphoma (n = 3), Ewing's sarcoma (n = 3), osteosarcoma (n = 1), and leukemia (n = 1). MRI studies were performed at 21 marrow sites to evaluate residual or recurrent tumor and were correlated with histologic material from the same site. T1- and T2-weighted sequences were employed in 21 and 14 studies, respectively; short tau inversion recovery (STIR) in 18; and static gadolinium diethylene triamine pentaacetic acid (Gd-DPTA)-enhanced. T1-weighted sequences in 13. All MRI studies showed an altered bone marrow signal. Technetium 99m methylene diphosphonate (99mTc-MDP) bone scintigraphy was also performed (19 studies). On histologic examination, 7 marrow specimens contained tumor, and 14 did not. Of the 7 tumor-positive lesions, all T1-weighted, 4 of 6 T2-weighted, and all 6 STIR sequences showed abnormal signal; all 5 Gd-DTPA-enhanced. T1-weighted sequences showed enhancement of the lesion. However, abnormal signals were also observed on all T1-weighted, 6 of 8 T2-weighted, 11 of 12 STIR, and 5 of 8 Gd-DTPA-enhanced, T1-weighted images of the tumor-negative sites. In this clinical setting, MRI did not consistently differentiate changes associated with treatment from malignant disease.