RESUMO
Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as an approach for generating patient-matched nuclear transfer (NT)-ESCs for studies of disease mechanisms and for developing specific therapies. Past attempts to produce human NT-ESCs have failed secondary to early embryonic arrest of SCNT embryos. Here, we identified premature exit from meiosis in human oocytes and suboptimal activation as key factors that are responsible for these outcomes. Optimized SCNT approaches designed to circumvent these limitations allowed derivation of human NT-ESCs. When applied to premium quality human oocytes, NT-ESC lines were derived from as few as two oocytes. NT-ESCs displayed normal diploid karyotypes and inherited their nuclear genome exclusively from parental somatic cells. Gene expression and differentiation profiles in human NT-ESCs were similar to embryo-derived ESCs, suggesting efficient reprogramming of somatic cells to a pluripotent state.
Assuntos
Linhagem Celular , Células-Tronco Embrionárias/citologia , Fibroblastos/citologia , Técnicas de Transferência Nuclear , Adulto , Animais , Blastocisto/citologia , Fusão Celular , Núcleo Celular/genética , Separação Celular , Feminino , Feto/citologia , Humanos , Macaca mulatta , Mitocôndrias/genética , Oócitos/citologia , Oócitos/metabolismo , Pele/citologiaRESUMO
Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg's cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle-chromosomal complex transfer). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%); however, a significant portion of ST zygotes (52%) showed abnormal fertilization as determined by an irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell isolation (38%) rates were comparable to controls. All embryonic stem cell lines derived from ST zygotes had normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls.
Assuntos
Terapia Genética , Doenças Mitocondriais/genética , Doenças Mitocondriais/terapia , Técnicas de Transferência Nuclear/normas , Adulto , Animais , Núcleo Celular/genética , Criopreservação , Citoplasma/genética , DNA Mitocondrial/análise , DNA Mitocondrial/genética , Embrião de Mamíferos/embriologia , Células-Tronco Embrionárias/citologia , Feminino , Fertilização , Humanos , Macaca mulatta/genética , Macaca mulatta/crescimento & desenvolvimento , Repetições de Microssatélites/genética , Oócitos/citologia , Gravidez , Adulto Jovem , Zigoto/citologia , Zigoto/patologiaRESUMO
OBJECTIVE: Whole-brain computed tomography perfusion (CTP) data sets generated by tracer delay-insensitive singular value decomposition plus (SVD+) and standard singular value decomposition (sSVD) deconvolution algorithms were evaluated to quantify relatedness and discrepancies in CTP results. METHODS: Twenty females with symmetrical hemispheric CTP maps indicative of brain tissue without apparent abnormalities were studied. Tissue-specific CTP values were analyzed. RESULTS: Standard SVD values were higher than SVD+ for cerebral blood flow. Other CTP values had minimal differences across brain regions. All simple linear regression models were statistically significant (P < 0.05) except for cerebral blood flow in white matter (P = 0.06). Cerebral blood volume had a good model fit, and mean transit time, a poor fit. CONCLUSIONS: Corresponding fitted CTP values for sSVD and SVD+ based on regression equations for brain-tissue types are presented. Additional research is required to compare SVD+ and sSVD in disease states when significant hemodynamic brain alterations are present.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Ácidos Tri-Iodobenzoicos/farmacocinética , Adulto , Algoritmos , Área Sob a Curva , Volume Sanguíneo , Isquemia Encefálica/diagnóstico por imagem , Circulação Cerebrovascular , Traumatismos Craniocerebrais/diagnóstico por imagem , Feminino , Cefaleia/diagnóstico por imagem , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Doses de Radiação , Valores de Referência , Estudos RetrospectivosRESUMO
Thoracic endometriosis syndrome is a well-described, rare manifestation of endometriosis. We present a case of a 35-year old woman undergoing controlled ovarian stimulation prior to in vitro fertilization (IVF) who developed bilateral hemorrhagic pleural effusions. She was initially diagnosed with ovarian hyperstimulation syndrome, a complication of infertility therapy; however, she was later found to have occult thoracic endometriosis. We describe ovarian hyperstimulation syndrome and review the manifestations of thoracic endometriosis syndrome. Although endometriosis is a hormone-dependent disease, the rate of IVF complications related to endometriosis is low.
Assuntos
Endometriose/diagnóstico , Pulmão/patologia , Síndrome de Hiperestimulação Ovariana/diagnóstico , Indução da Ovulação/efeitos adversos , Doenças Torácicas/diagnóstico , Adulto , Erros de Diagnóstico , Endometriose/complicações , Feminino , Fertilização in vitro , Humanos , Hidropneumotórax/diagnóstico por imagem , Hidropneumotórax/etiologia , Derrame Pleural/diagnóstico por imagem , Radiografia , Doenças Torácicas/complicaçõesRESUMO
CONTEXT: Vascular endothelial growth factor A (VEGF-A) is a potent cytokine that promotes angiogenesis and vascular permeability. After controlled ovarian stimulation (COS) for in vitro fertilization (IVF), excessive VEGF-A production can occur, particularly in women with polycystic ovarian syndrome (PCOS); however, it is unclear whether the regulation of VEGF-A production is different between PCOS and non-PCOS women. OBJECTIVE: The aim of this study was to determine whether there were differences in the dose- and time-dependent effects of insulin and IGFs on VEGF-A production by luteinized granulosa cells (LGCs) from women with and without PCOS. DESIGN AND SETTING: A prospective comparative experimental study was conducted at an institutional practice. PATIENTS: Patients included six PCOS and six non-PCOS women undergoing COS and IVF. INTERVENTIONS: Interventions included COS for IVF. MAIN OUTCOME MEASURES: VEGF-A levels in culture media were collected daily for 3 d from LGCs after incubation with variable doses of insulin, IGF-I, and IGF-II in the presence and absence of LH. RESULTS: In both study groups, exposure to LH alone did not alter VEGF-A levels. However, insulin or IGF increased VEGF-A levels within 1 d and appeared to synergize with LH at 3 d. VEGF-A production by non-PCOS LGCs was more sensitive to IGF exposure, whereas PCOS cells were more sensitive to insulin. Although an increase in DNA content (P < 0.05) was noted in cultures of PCOS cells, progesterone levels were lower compared with non-PCOS LGCs. CONCLUSION: Insulin and IGFs promote VEGF-A production in LGCs, but the response patterns are different when cells from PCOS and non-PCOS women are compared.
Assuntos
Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Síndrome do Ovário Policístico/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Células Cultivadas , Meios de Cultura/farmacologia , Feminino , Fertilização in vitro , Células da Granulosa/citologia , Humanos , Hipoglicemiantes/metabolismo , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like II/farmacologia , Luteinização , Hormônio Luteinizante/farmacologia , Indução da OvulaçãoRESUMO
UNLABELLED: The toxicity of red bone marrow is widely considered to be a key factor in restricting the activity administered in molecular radiotherapy to suboptimal levels. The assessment of marrow toxicity requires an assessment of the dose absorbed by red bone marrow which, in many cases, requires knowledge of the total red bone marrow mass in a given patient. Previous studies demonstrated, however, that a close surrogate-spongiosa volume (combined tissues of trabecular bone and marrow)-can be used to accurately scale reference patient red marrow dose estimates and that these dose estimates are predictive of marrow toxicity. Consequently, a predictive model of the total skeletal spongiosa volume (TSSV) would be a clinically useful tool for improving patient specificity in skeletal dosimetry. METHODS: In this study, 10 male and 10 female cadavers were subjected to whole-body CT scans. Manual image segmentation was used to estimate the TSSV in all 13 active marrow-containing skeletal sites within the adult skeleton. The age, total body height, and 14 CT-based skeletal measurements were obtained for each cadaver. Multiple regression was used with the dependent variables to develop a model to predict the TSSV. RESULTS: Os coxae height and width were the 2 skeletal measurements that proved to be the most important parameters for prediction of the TSSV. The multiple R(2) value for the statistical model with these 2 parameters was 0.87. The analysis revealed that these 2 parameters predicted the estimated the TSSV to within approximately +/-10% for 15 of the 20 cadavers and to within approximately +/-20% for all 20 cadavers in this study. CONCLUSION: Although the utility of spongiosa volume in estimating patient-specific active marrow mass has been shown, estimation of the TSSV in active marrow-containing skeletal sites via patient-specific image segmentation is not a simple endeavor. However, the alternate approach demonstrated in this study is fairly simple to implement in a clinical setting, as the 2 input measurements (os coxae height and width) can be made with either pelvic CT scanning or skeletal radiography.
Assuntos
Medula Óssea/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Radiometria/métodos , Medula Óssea/patologia , Osso e Ossos/efeitos da radiação , Cadáver , Feminino , Humanos , Modelos Lineares , Masculino , Modelos Químicos , Dosagem Radioterapêutica , Análise de Regressão , Tomografia Computadorizada por Raios X/métodos , Imagem Corporal TotalRESUMO
UNLABELLED: Toxicity of the hematopoietically active bone marrow continues to be a primary limitation in radionuclide therapies of cancer. Improved techniques for patient-specific skeletal dosimetry are thus crucial to the development of dose-response relationships needed to optimize these therapies (i.e., avoid both marrow toxicity and tumor underdosing). Current clinical methods of skeletal dose assessment rely heavily on a single set of bone and marrow cavity chord-length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired-image radiation transport (PIRT) model that can provide a more realistic 3-dimensional geometry for particle transport of the skeletal site at both microscopic and macroscopic levels of its histology. METHODS: Ex vivo CT scans were acquired of the lumbar vertebra and right proximal femur excised from a 66-y male cadaver (body mass index, 22.7 kg m(-2)). For both skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were then taken and subjected to nuclear magnetic resonance (NMR) microscopy. Voxels within the resulting NMR microimages were segmented and labeled into regions of bone trabeculae, endosteum, active marrow, and inactive marrow. The PIRT methodology was then implemented within the EGSnrc radiation transport code, whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the NMR microimage of the skeletal site. RESULTS: At electron initial energies greater than 50-200 keV, a divergence in absorbed fractions to active marrow is noted between PIRT model simulations and those estimated under infinite spongiosa transport techniques. Calculations of radionuclide S values under both methodologies imply that current chord-based models used in clinical skeletal dosimetry can overestimate dose to active bone marrow in these 2 skeletal sites by approximately 4%-23% for low-energy beta-emitters ((33)P, (169)Er, and (177)Lu), by approximately 4%-25% for intermediate-energy beta-emitters ((153)Sm, (186)Re, and (89)Sr), and by approximately 11%-30% for high-energy beta-emitters ((32)P, (188)Re, and (90)Y). CONCLUSION: The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow-containing bones within the skeleton, thus permitting improved estimates of absorbed fractions and radionuclide S values for intermediate-to-high beta-emitters.
Assuntos
Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiopatologia , Espectroscopia de Ressonância Magnética/métodos , Modelos Biológicos , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Algoritmos , Carga Corporal (Radioterapia) , Osso e Ossos/efeitos da radiação , Cadáver , Simulação por Computador , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Transferência Linear de Energia , Masculino , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Técnica de SubtraçãoRESUMO
UNLABELLED: Alpha-particles are of current interest in radionuclide therapy due to their short range and high rates of energy transfer to target tissues. Published values of alpha-particle absorbed fraction phi in the skeletal tissues, as needed for patient-specific dosimetry under the MIRD schema, do not generally account for its variation with particle energy or skeletal site. Furthermore, variations in alpha-particle absorbed fraction with marrow cellularity have yet to be fully considered. METHODS: In this study, a 3-dimensional (3D) chord-based radiation transport model (or 3D-CBIST) is presented, which combines (a) chord-based techniques for tracking alpha-particles across bone trabeculae, endosteum, and marrow cavities and (b) a spatial model of the marrow tissues that explicitly considers the presence of marrow adipocytes. Chord-length distributions are taken from a 44-y male subject (ICRP [International Commission on Radiological Protection] Reference Male) and are identical to those used currently for clinical dose estimates for beta-particle emitters. RESULTS: Values of phi(active marrow<--active marrow) given by the 3D-CBIST model are shown to be considerably lower than phi = 1.0 assumed under the ICRP Publication 30 and 2003 Eckerman bone models. For example, values of absorbed fraction for the self-dose to active bone marrow in the ribs, cervical vertebra, and parietal bone are 0.81, 0.80, and 0.55 for 6-MeV alpha-particles and are 0.74, 0.72, and 0.43 for 9-MeV alpha-particles, where each is evaluated at ICRP reference cellularities in the 3D-CBIST model (72%, 72%, and 42%, respectively, at age 25 y). CONCLUSION: Improvements in patient-specific dosimetry of skeletal tissues require explicit consideration of not only changes in target mass with variable patient marrow cellularity (i.e., active marrow) but also corresponding changes in values of the absorbed fraction. The data given in this study provide a more-firm basis for application of the MIRD schema to patient-specific dosimetry for newly developing therapies using alpha-particle emitters.
Assuntos
Partículas alfa , Medula Óssea/fisiologia , Osso e Ossos/fisiologia , Modelos Biológicos , Radiometria/métodos , Adulto , Carga Corporal (Radioterapia) , Medula Óssea/efeitos da radiação , Simulação por Computador , Humanos , Transferência Linear de Energia/fisiologia , Masculino , Doses de Radiação , Radiometria/normas , Valores de Referência , Eficiência Biológica RelativaRESUMO
Current methods of skeletal dose assessment in both medical physics (radionuclide therapy) and health physics (dose reconstruction and risk assessment) rely heavily on a single set of bone and marrow cavity chord-length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired-image radiation transport (PIRT) model which provides a more realistic three-dimensional (3D) geometry for particle transport in the skeletal site at both microscopic and macroscopic levels of its histology. Ex vivo CT scans were acquired of the pelvis, cranial cap, and individual ribs excised from a 66-year male cadaver (BMI of 22.7 kg m(-2)). For the three skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were taken and subjected to microCT imaging. Voxels within the resulting microCT images were then segmented and labeled as regions of bone trabeculae, endosteum, active marrow, and inactive marrow through application of image processing algorithms. The PIRT methodology was then implemented within the EGSNRC radiation transport code whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the CT microimage of the skeletal site. At initial electron energies greater than 50-200 keV, a divergence in absorbed fractions to active marrow are noted between PIRT model simulations and those estimated under existing techniques of infinite spongiosa transport. Calculations of radionuclide S values under both methodologies imply that current chord-based models may overestimate the absorbed dose to active bone marrow in these skeletal sites by 0% to 27% for low-energy beta emitters (33P, 169Er, and 177Lu), by approximately 4% to 49% for intermediate-energy beta emitters (153Sm, 186Re, and 89Sr), and by approximately 14% to 76% for high-energy beta emitters (32p, 188Re, and 90Y). The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow-containing bones within the skeleton thus permitting improved estimates of absorbed fractions and radionuclide S values for intermediate-to-high energy beta emitters.
Assuntos
Partículas beta , Densidade Óssea/fisiologia , Osso e Ossos/fisiologia , Osso e Ossos/efeitos da radiação , Transferência Linear de Energia/fisiologia , Modelos Biológicos , Radiometria/métodos , Idoso , Algoritmos , Carga Corporal (Radioterapia) , Densidade Óssea/efeitos da radiação , Osso e Ossos/diagnóstico por imagem , Cadáver , Simulação por Computador , Humanos , Masculino , Especificidade de Órgãos , Doses de Radiação , Radiografia , Planejamento da Radioterapia Assistida por Computador/métodos , Eficiência Biológica RelativaRESUMO
Anatomic models needed for internal dose assessment have traditionally been developed using mathematical surface equations to define organ boundaries, shapes, and their positions within the body. Many researchers, however, are now advocating the use of tomographic models created from segmented patient computed tomography (CT) or magnetic resonance (MR) scans. In the skeleton, however, the tissue structures of the bone trabeculae, marrow cavities, and endosteal layer are exceedingly small and of complex shape, and thus do not lend themselves easily to either stylistic representations or in-vivo CT imaging. Historically, the problem of modeling the skeletal tissues has been addressed through the development of chord-based methods of radiation particle transport, as given by studies at the University of Leeds (Leeds, U.K.) using a 44-year male subject. We have proposed an alternative approach to skeletal dosimetry in which excised sections of marrow-intact cadaver spongiosa are imaged directly via microCT scanning. The cadaver selected for initial investigation of this technique was a 66-year male subject of nominal body mass index (22.7 kg m(-2)). The objectives of the present study were to compare chord-based versus voxel-based methods of skeletal dosimetry using data from the UF 66-year male subject. Good agreement between chord-based and voxel-based transport was noted for marrow irradiation by either bone surface or bone volume sources up to 500-1000 keV (depending upon the skeletal site). In contrast, chord-based models of electron transport yielded consistently lower values of the self-absorbed fraction to marrow tissues than seen under voxel-based transport at energies above 100 keV, a feature directly attributed to the inability of chord-based models to account for nonlinear electron trajectories. Significant differences were also noted in the dosimetry of the endosteal layer (for all source tissues), with chord-based transport predicting a higher fraction of energy deposition than given by voxel-based transport (average factor of about 1.6). The study supports future use of voxel-based skeletal models which (1) permit nonlinear electron trajectories across the skeletal tissues, (2) do not rely on mathematical algorithms for treating the endosteal tissue layer, and (3) do not implicitly assume independence of marrow and bone trajectories as is the case for chord-based skeletal models.
Assuntos
Algoritmos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiologia , Transporte de Elétrons/fisiologia , Modelos Biológicos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiometria/métodos , Idoso , Cadáver , Simulação por Computador , Humanos , Masculino , Doses de Radiação , Espalhamento de RadiaçãoRESUMO
In radiation protection, skeletal dose estimates are required for the tissues of the hematopoietically active bone marrow and the osteogenic cells of the trabecular and cortical endosteum. Similarly, skeletal radiation dose estimates are required in therapy nuclear medicine in order to develop dose-response functions for myelotoxicity where active bone marrow is generally the dose-limiting organ in cancer radioimmunotherapy. At the present time, skeletal dose models in both radiation protection and medical dosimetry are fundamentally reliant on a single set of chord-length distribution measurements performed at the University of Leeds in the late 1970's for a 44-y-old male subject. These distributions describe the relative frequency at which linear pathlengths are seen across both the marrow cavities and bone trabeculae in seven individual bone sites: vertebrae (cervical and lumbar), proximal femur (head and neck), ribs, cranium (parietal bone), and pelvis (iliac crest). In the present study, we present an alternative set of chord-length distribution data acquired within a total of 14 skeletal sites of a 66-y-old male subject. The University of Florida (UF) distributions are assembled via 3D image processing of microCT scans of physical sections of trabecular spongiosa at each skeletal site. In addition, a tri-linear interpolation Marching Cube algorithm is employed to smooth the digital surfaces of the bone trabeculae while chord-length measurements are performed. A review of mean chord lengths indicate that larger marrow cavities are noted on average in the UF individual for the cervical vertebrae (1,038 vs. 910 microm), lumbar vertebrae (1,479 vs. 1,233 microm), ilium (1,508 vs. 904 microm), and parietal bone (812 vs. 389 microm), while smaller marrow cavities are noted in the UF individual for the femoral head (1,043 microm vs. 1,157 microm), the femoral neck (1,454 microm vs. 1,655 microm), and the ribs (1,630 microm vs. 1,703 microm). The mean chord-lengths for the bone trabeculae show close agreement for both individuals in the ilium (approximately 240 microm) and cervical vertebrae (approximately 280 microm). Thicker trabeculae were seen on average in the UF individual for the femoral head (ratio of 1.50), femoral neck (ratio of 1.10), lumbar vertebrae (ratio of 1.29), and ribs (ratio of 1.14), while thinner trabeculae were seen on average in the UF individual for the parietal bone of the cranium (ratio of 0.92). In two bone sites, prominent discrepancies in chord distribution shape were noted between the Leeds 44-y-old male and the UF 66-y-old male: (1) the bone trabeculae in the ribs, and (2) the marrow cavities and bone trabeculae within the cranium.
Assuntos
Sistema Musculoesquelético/efeitos da radiação , Radiometria/métodos , Adulto , Fatores Etários , Idoso , Medula Óssea/patologia , Medula Óssea/efeitos da radiação , Colo do Fêmur/patologia , Colo do Fêmur/efeitos da radiação , Cabeça/patologia , Cabeça/efeitos da radiação , Humanos , Imageamento Tridimensional , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Sistema Musculoesquelético/patologia , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador , Costelas/patologia , Costelas/efeitos da radiação , Coluna Vertebral/patologia , Coluna Vertebral/efeitos da radiaçãoRESUMO
UNLABELLED: Few studies have been conducted to quantify the spatial distributions of adipocytes in the marrow cavities of trabecular bone. Nevertheless, such data are needed for the development of 3-dimensional (3D) voxel skeletal models where marrow cellularity is explicitly considered as a model parameter for dose assessment. In this investigation, bone marrow biopsies of the anterior iliac crest were examined to determine the size distribution of adipocyte cell clusters, the percentage of perimeter coverage of trabecular surfaces, and the presence or absence of adipocyte density gradients in the marrow space, all as a function of the biopsy marrow cellularity (5%-95%). METHODS: Biopsy slides from 42 patients were selected as designated by the hematopathologist as either normocellular or with no evidence of disease. Still-frame video image captures were made of 1-3 regions of interest per biopsy specimen, with subsequent image analysis of adipocyte spatial characteristics performed via a user-written MATLAB routine. RESULTS: A predictable shift was found in cluster size with decreasing marrow cellularity from single adipocytes to clusters of >or=3 cells; the percentage of 2-cell clusters remained relatively constant with changing cellularity. Also, a nonlinear increase in trabeculae perimeter coverage was found with increasing fat tissue fraction at marrow cellularities between 50% and 80%. Finally, it was demonstrated that only in the range of 20%-50% marrow cellularity was a slight gradient in adipocyte concentration indicated with adipocytes localized preferentially toward the trabecular surfaces. CONCLUSION: Electron transport simulations were conducted in 4 different 3D voxel models of trabecular bone for sources localized in the active marrow (TAM), bone volume (TBV), bone endosteum (TBE), and bone surfaces (TBS). Voxel model simulations demonstrated that absorbed fractions to active marrow given by the ICRP 30 model (MIRDOSE2) are exceedingly conservative for both TBV and TBS sources, except in the case of high-energy particles (>500 keV) at high values of marrow cellularity (>70%). Values of both phi(TAM<--TBV) and phi(TAM<--TBS) given by the Eckerman and Stabin model (MIRDOSE3) were shown to be reasonably consistent with 3D voxel model simulations at the reference cellularity of 25%, except in the case of low-energy emitters (<100 keV) on the bone surfaces.
Assuntos
Adipócitos/citologia , Células da Medula Óssea/citologia , Osso e Ossos/efeitos da radiação , Doses de Radiação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Elétrons , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
UNLABELLED: Dose assessment to active bone marrow is a critical feature of radionuclide therapy treatment planning. Skeletal dosimetry models currently used to assign radionuclide S values for clinical marrow dose assessment are based on bone and marrow cavity chord-length distributions. Accordingly, these models cannot explicitly consider energy loss to inactive marrow (adipose tissue) during particle transport across the trabecular marrow space (TMS). One method to account for this energy loss is to uniformly scale the resulting TMS absorbed fractions by reference values of site-specific marrow cellularity. In doing so, however, the resulting absorbed fractions for self-irradiation of the trabecular active marrow (TAM) do not converge to unity at low electron source energies. This study attempts to address this issue by using nuclear magnetic resonance microscopy images of trabecular bone to define 3-dimensional (3D) dosimetric models in which explicit spatial distributions of adipose tissue are introduced. METHODS: Cadaveric sources of trabecular bone were taken from both the femoral heads and humeral epiphyses of a 51-y-old male subject. The bone sites were sectioned and subsequently imaged at a proton resonance frequency of 200 MHz (4.7 T) using a 3D spin-echo pulse sequence. After image segmentation, voxel clusters of adipocytes were inserted interior to the marrow cavities of the binary images, which were then coupled to the EGS4 radiation transport code for simulation of active marrow electron sources. RESULTS: Absorbed fractions for self-irradiation of the TAM were tabulated for both skeletal sites. Substantial variations in the absorbed fraction to active marrow are seen with changes in marrow cellularity, particularly in the energy range of 100-500 keV. These variations are seen to be more dramatic in the humeral epiphysis (larger marrow volume fraction) than in the femoral head. CONCLUSION: Results from electron transport in 3D models of the trabecular skeleton indicate that current methods to account for marrow cellularity in chord-based models are incomplete. At 10 keV, for example, the Eckerman and Stabin model underestimates the self-absorbed fraction to active marrow by 75%. At 1 MeV, the model of Bouchet et al. overestimates this same value by 40%. In the energy range of 20-200 keV, neither model accurately predicts energy loss to the active bone marrow. Thus, it is proposed that future extensions of skeletal dosimetry models use 3D transport techniques in which explicit delineation of active and inactive marrow is feasible.
Assuntos
Medula Óssea/patologia , Osso e Ossos/efeitos da radiação , Doses de Radiação , Adipócitos/efeitos da radiação , Medula Óssea/efeitos da radiação , Cadáver , Cabeça do Fêmur/efeitos da radiação , Humanos , Úmero/efeitos da radiação , Imageamento Tridimensional , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radiometria , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To evaluate alternatives for couples with severe male factor infertility who fail to conceive with IVF-intracytoplasmic sperm injection (ICSI). DESIGN: Outcomes of couples using artificial insemination with donor sperm (AID) after failed IVF-ICSI, assessing multiple risk factors affecting prognosis. SETTING: University infertility service. PATIENT(S): Nineteen patients with complex infertility disorders who failed IVF-ICSI and subsequently used AID (1 to 7 cycles). INTERVENTION(S): Artificial insemination with donor sperm was performed 36 hours after detection of an LH surge or hCG injection. MAIN OUTCOME MEASURE(S): Pregnancy outcomes were determined. RESULT(S): Seventeen pregnancies occurred in 16 women associated with AID for a pregnancy rate per cycle of 27.9% within a mean of 3.2 +/- 18 cycles. Live birth rate per cycle was 24.6%. CONCLUSION(S): A high pregnancy rate was achieved with AID in women who failed IVF-ICSI. Given the low cost and effectiveness of AID in this series, consideration of AID is a reasonable and effective option even in couples with poor prognosis who fail to conceive with IVF-ICSI.
Assuntos
Fertilização in vitro , Infertilidade/terapia , Inseminação Artificial Heteróloga , Resultado da Gravidez , Injeções de Esperma Intracitoplásmicas , Adulto , Coeficiente de Natalidade , Feminino , Humanos , Masculino , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Doadores de Tecidos , Falha de TratamentoRESUMO
IMPORTANCE: In the last 3 years, we have witnessed the publication of multiple but conflicting guidelines on the management of hypothyroidism during pregnancy. Hypothyroidism is one of the most common endocrinopathies in reproductive-age and pregnant women. Given the prevalence of thyroid disease, it is highly likely that obstetricians will encounter and provide care for pregnant women with thyroid disease. Therefore, a review of current guidelines and management options is clinically relevant. OBJECTIVES: Our goals are to review the changes in thyroid function during pregnancy, the options for testing for thyroid disease, the different categories of thyroid dysfunction and surveillance strategies among subspecialty societies, and the obstetric hazards associated with thyroid dysfunction and review the evidence for benefit of treatment options for thyroid disease. EVIDENCE ACQUISITION: We reviewed key subspecialty guidelines, as well as current and ongoing studies focused on the treatment of hypothyroidism during pregnancy. RESULTS: There are significant differences in the identification and management of thyroid disease during pregnancy among subspecialists. We present our recommendations based on the available evidence. RELEVANCE: Evidence exists that obstetricians struggle with the diagnosis and treatment of hypothyroidism. According to recent surveys, the management of hypothyroidism during pregnancy is the number 1 endocrine topic of interest for obstetricians. A synopsis of recently published subspecialty guidelines is timely. CONCLUSIONS: Recent, evidence-based findings indicate that obstetricians should consider modifying their approach to the identification and treatment of thyroid disease during pregnancy.
Assuntos
Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Guias de Prática Clínica como Assunto , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Doenças Assintomáticas/terapia , Autoanticorpos/sangue , Feminino , Humanos , Hipotireoidismo/imunologia , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Iodo/deficiência , Gravidez , Complicações na Gravidez/imunologia , Trimestres da Gravidez , Glândula Tireoide/fisiologia , Tireotropina/sangue , Tiroxina/sangue , Tiroxina/uso terapêuticoRESUMO
OBJECTIVE: To compare the precision of progesterone measurements obtained with the use of immunoassays and of liquid chromatography-tandem mass spectrometry (LC-MS/MS). DESIGN: Comparative study. SETTING: Academic, private practice, and in vitro fertilization (IVF) research centers. PATIENT(S): A total of 189 human serum samples were collected during controlled ovarian hyperstimulation and early pregnancy in women undergoing IVF. INTERVENTION(S): Serum progesterone pools (n = 10; 0.2-4 ng/mL) were sent to four laboratory centers that used four different automated immunoassay analyzers. Progesterone was measured by immunoassay in triplicate at three separate time points (n = 9 per pool) and by LC-MS/MS in triplicate once (n = 3 per pool). MAIN OUTCOME MEASURE(S): Inter- and intraassay coefficients of variation (CVs) of progesterone measurements were compared for each analyzer and LC-MS/MS. RESULT(S): Progesterone measurements by immunoassay were highly correlated with those by LC-MS/MS. Only two analyzers had intraassay CVs <10% at all three experimental time points, and only two analyzers had an interassay CV <10%. Mean progesterone levels by the analyzers were different across multiple progesterone pools. CONCLUSION(S): Our results indicate that progesterone threshold measurements used for IVF clinical decisions should be interpreted cautiously and based on laboratory- and method-specific data. A validated progesterone standard incorporated into daily immunoassays could improve medical decision accuracy.
Assuntos
Fertilização in vitro , Imunoensaio/normas , Infertilidade/terapia , Indução da Ovulação , Progesterona/sangue , Automação Laboratorial/normas , Biomarcadores/sangue , Cromatografia Líquida/normas , Desenho de Equipamento , Feminino , Humanos , Imunoensaio/instrumentação , Infertilidade/sangue , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Ensaio de Proficiência Laboratorial , Variações Dependentes do Observador , Seleção de Pacientes , Valor Preditivo dos Testes , Gravidez , Taxa de Gravidez , Reprodutibilidade dos Testes , Estudos Retrospectivos , Espectrometria de Massas em Tandem/normas , Estados UnidosRESUMO
OBJECTIVE: To compare rates of dyspareunia in infertile women and healthy controls. Secondary aims are to determine whether demographic characteristics, rates of sexual dysfunction, and baseline depression status differ between the two groups. DESIGN: A case-control study. SETTING: University-based faculty fertility and OB/GYN generalist clinics. PATIENT(S): Seventy-five infertile female subjects presenting to the infertility clinic and 210 women presenting to the generalist clinic for their annual exam. INTERVENTION(S): Completion of an anonymous survey including demographic information, the Female Sexual Function Index (FSFI), Patient-Health Questionnaire-9 (PHQ-9), and original questions regarding sexual pain. MAIN OUTCOME MEASURE(S): Rate of dyspareunia and sexual dysfunction. RESULT(S): There were no significant differences in rates of dyspareunia (37.6% controls vs. 30.7% study) or the rate of sexual dysfunction (31.9% controls vs. 37.3% study). Infertile women had more frequent intercourse than controls and were more likely to be married. There were otherwise no differences in baseline rates of depression, demographic characteristics, or individual domain scores of the FSFI. CONCLUSION(S): Women seeking fertility treatment had similar rates of dyspareunia and sexual dysfunction compared with controls.
Assuntos
Depressão/epidemiologia , Infertilidade Feminina/epidemiologia , Estado Civil/estatística & dados numéricos , Técnicas de Reprodução Assistida/estatística & dados numéricos , Disfunções Sexuais Fisiológicas/epidemiologia , Saúde da Mulher/estatística & dados numéricos , Adolescente , Adulto , Comorbidade , Dispareunia , Feminino , Humanos , Oregon/epidemiologia , Medição de Risco , Adulto JovemRESUMO
OBJECTIVE: To determine whether angiopoietin (ANGPT)-1 and -2 are detectable in the circulation of nonhuman primates and women and whether these levels fluctuate in association with ovarian activity. DESIGN: Prospective. SETTING: National Primate Research Center, medical center, and infertility clinic. PATIENT(S): Adult female rhesus monkeys; 15 women donating oocytes for infertility treatment. INTERVENTION(S): Controlled ovarian stimulation with gonadotropins, removal of the corpus luteum and ovaries, oocyte retrieval, and ET. MAIN OUTCOME MEASURE(S): Circulating levels of ANGPT-1 and ANGPT-2. RESULT(S): Serum ANGPT-1 and ANGPT-2 levels were detectable and invariant in maintaining an ANGPT-1 to -2 ratio >1 in [1] macaques over the course of the natural menstrual cycle, during a controlled ovulation protocol, and after removal of the corpus luteum or ovaries and [2] women undergoing controlled ovarian simulation. In contrast, the ANGPT-1 to -2 ratio was markedly decreased (<<1) at mid-to-late gestation in macaques and in the follicular fluid of women undergoing controlled ovarian simulation because of increased levels of ANGPT-2. CONCLUSION(S): The ovary and its dominant structures are not major contributors to circulating levels of ANGPT-1 or ANGPT-2. The physiologic importance of the rising levels of ANGPT-2 after the luteal-placental shift in pregnancy is unknown.
Assuntos
Angiopoietina-1/sangue , Angiopoietina-2/sangue , Ciclo Menstrual/sangue , Indução da Ovulação , Adulto , Animais , Feminino , Líquido Folicular/metabolismo , Idade Gestacional , Humanos , Macaca mulatta , Gravidez , Estudos Prospectivos , Fatores de TempoRESUMO
Circulating levels of Ang-2 and sTie-2 receptor were detectable but invariant in women during COS cycles. During the postimplantation period, the rise in Ang-2 (but not sTie-2) levels probably reflects placental rather than luteal production.