Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Am Med Inform Assoc ; 29(2): 271-284, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34486655

RESUMO

There are over 1 million transgender people living in the United States, and 33% report negative experiences with a healthcare provider, many of which are connected to data representation in electronic health records (EHRs). We present recommendations and common pitfalls involving sex- and gender-related data collection in EHRs. Our recommendations leverage the needs of patients, medical providers, and researchers to optimize both individual patient experiences and the efficacy and reproducibility of EHR population-based studies. We also briefly discuss adequate additions to the EHR considering name and pronoun usage. We add the disclaimer that these questions are more complex than commonly assumed. We conclude that collaborations between local transgender and gender-diverse persons and medical providers as well as open inclusion of transgender and gender-diverse individuals on terminology and standards boards is crucial to shifting the paradigm in transgender and gender-diverse health.


Assuntos
Pessoas Transgênero , Coleta de Dados , Registros Eletrônicos de Saúde , Identidade de Gênero , Humanos , Reprodutibilidade dos Testes , Estados Unidos
2.
J Pediatr Hematol Oncol ; 41(5): 382-387, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31094908

RESUMO

Pseudomyogenic hemangioendothelioma (PMH) is a rare neoplasm with vascular and sarcomatous elements, unpredictable course, and uncommon metastatic or fatal potential. Although systemic chemotherapy has been reported with variable success, generally accepted treatment is aggressive surgery with wide margins. Evidence-based treatment options are lacking, and lack of clear prognostic features poses a risk of undertreatment or overtreatment with associated morbidity and mortality. We report the use of initial systemic therapy with oral sirolimus (SIR) and IV zoledronic acid (ZA) to induce a sustained clinical response and avoidance of amputation in a 6-year-old boy. At 37 months after diagnosis, our patient remains in sustained clinical remission as documented by x-ray, MRI, and PET-CT with return of normal mobility/activity and resolution of swelling and pain. Literature review identified 20 cases of pediatric and young adult patients with PMH, of which 7 received some form of systemic therapy. To the best of our knowledge, our patient represents the youngest reported case of PMH and the first successful and limb-sparing utilization of systemic chemotherapy as primary treatment for PMH.


Assuntos
Hemangioendotelioma/tratamento farmacológico , Sirolimo/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Criança , Hemangioendotelioma/diagnóstico por imagem , Humanos , Masculino , Imagem Multimodal/métodos
3.
J Am Heart Assoc ; 5(8)2016 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-27464788

RESUMO

BACKGROUND: Despite public awareness that tobacco secondhand smoke (SHS) is harmful, many people still assume that marijuana SHS is benign. Debates about whether smoke-free laws should include marijuana are becoming increasingly widespread as marijuana is legalized and the cannabis industry grows. Lack of evidence for marijuana SHS causing acute cardiovascular harm is frequently mistaken for evidence that it is harmless, despite chemical and physical similarity between marijuana and tobacco smoke. We investigated whether brief exposure to marijuana SHS causes acute vascular endothelial dysfunction. METHODS AND RESULTS: We measured endothelial function as femoral artery flow-mediated dilation (FMD) in rats before and after exposure to marijuana SHS at levels similar to real-world tobacco SHS conditions. One minute of exposure to marijuana SHS impaired FMD to a comparable extent as impairment from equal concentrations of tobacco SHS, but recovery was considerably slower for marijuana. Exposure to marijuana SHS directly caused cannabinoid-independent vasodilation that subsided within 25 minutes, whereas FMD remained impaired for at least 90 minutes. Impairment occurred even when marijuana lacked cannabinoids and rolling paper was omitted. Endothelium-independent vasodilation by nitroglycerin administration was not impaired. FMD was not impaired by exposure to chamber air. CONCLUSIONS: One minute of exposure to marijuana SHS substantially impairs endothelial function in rats for at least 90 minutes, considerably longer than comparable impairment by tobacco SHS. Impairment of FMD does not require cannabinoids, nicotine, or rolling paper smoke. Our findings in rats suggest that SHS can exert similar adverse cardiovascular effects regardless of whether it is from tobacco or marijuana.


Assuntos
Poluição do Ar/efeitos adversos , Endotélio Vascular/efeitos dos fármacos , Fumar Maconha/efeitos adversos , Fumaça/efeitos adversos , Animais , Circulação Coronária/efeitos dos fármacos , Feminino , Óxido Nítrico/metabolismo , Nitroglicerina/farmacologia , Doenças Vasculares Periféricas/etiologia , Doenças Vasculares Periféricas/fisiopatologia , Ratos Sprague-Dawley , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
4.
J Am Heart Assoc ; 5(1)2016 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-26738788

RESUMO

BACKGROUND: Circulating angiogenic cells (CACs) are peripheral blood cells whose functional capacity inversely correlates with cardiovascular risk and that have therapeutic benefits in animal models of cardiovascular disease. However, donor age and disease state influence the efficacy of autologous cell therapy. We sought to determine whether age or coronary artery disease (CAD) impairs the therapeutic potential of CACs for myocardial infarction (MI) and whether the use of ex vivo gene therapy to overexpress endothelial nitric oxide (NO) synthase (eNOS) overcomes these defects. METHODS AND RESULTS: We recruited 40 volunteers varying by sex, age (< or ≥45 years), and CAD and subjected their CACs to well-established functional tests. Age and CAD were associated with reduced CAC intrinsic migration (but not specific response to vascular endothelial growth factor, adherence of CACs to endothelial tubes, eNOS mRNA and protein levels, and NO production. To determine how CAC function influences therapeutic potential, we injected the 2 most functional and the 2 least functional CAC isolates into mouse hearts post MI. The high-function isolates substantially improved cardiac function, whereas the low-function isolates led to cardiac function only slightly better than vehicle control. Transduction of the worst isolate with eNOS cDNA adenovirus increased NO production, migration, and cardiac function of post-MI mice implanted with the CACs. Transduction of the best isolate with eNOS small interfering RNA adenovirus reduced all of these capabilities. CONCLUSIONS: Age and CAD impair multiple functions of CACs and limit therapeutic potential for the treatment of MI. eNOS gene therapy in CACs from older donors or those with CAD has the potential to improve autologous cell therapy outcomes.


Assuntos
Doença da Artéria Coronariana/enzimologia , Células Progenitoras Endoteliais/enzimologia , Células Progenitoras Endoteliais/transplante , Infarto do Miocárdio/cirurgia , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Transplante de Células-Tronco/métodos , Adulto , Idoso , Animais , Estudos de Casos e Controles , Movimento Celular , Células Cultivadas , Técnicas de Cocultura , Doença da Artéria Coronariana/diagnóstico , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos SCID , Pessoa de Meia-Idade , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Óxido Nítrico Sintase Tipo III/genética , Fenótipo , Interferência de RNA , Recuperação de Função Fisiológica , Regeneração , Transdução de Sinais , Fatores de Tempo , Transdução Genética , Transfecção
5.
Nat Commun ; 4: 2429, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24019001

RESUMO

Gain-of-function mutations of the isocitrate dehydrogenase 1 (IDH1) gene are among the most prevalent in low-grade gliomas and secondary glioblastoma. They lead to intracellular accumulation of the oncometabolite 2-hydroxyglutarate, represent an early pathogenic event and are considered a therapeutic target. Here we show, in this proof-of-concept study, that [1-(13)C] α-ketoglutarate can serve as a metabolic imaging agent for non-invasive, real-time, in vivo monitoring of mutant IDH1 activity, and can inform on IDH1 status. Using (13)C magnetic resonance spectroscopy in combination with dissolution dynamic nuclear polarization, the metabolic fate of hyperpolarized [1-(13)C] α-ketoglutarate is studied in isogenic glioblastoma cells that differ only in their IDH1 status. In lysates and tumours that express wild-type IDH1, only hyperpolarized [1-(13)C] α-ketoglutarate can be detected. In contrast, in cells that express mutant IDH1, hyperpolarized [1-(13)C] 2-hydroxyglutarate is also observed, both in cell lysates and in vivo in orthotopic tumours.


Assuntos
Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Glioma/enzimologia , Glioma/genética , Isocitrato Desidrogenase/genética , Animais , Isótopos de Carbono , Extratos Celulares , Linhagem Celular Tumoral , Análise Mutacional de DNA , Glutaratos/metabolismo , Humanos , Ácidos Cetoglutáricos/metabolismo , Espectroscopia de Ressonância Magnética , Proteínas Mutantes/metabolismo , Ratos , Ratos Nus
6.
PLoS One ; 8(4): e61413, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23630585

RESUMO

Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model.


Assuntos
Proteínas de Transporte/genética , Citocinas/genética , Terapia Genética , Isquemia/terapia , Músculo Esquelético/irrigação sanguínea , Fragmentos de Peptídeos/genética , Animais , Proteínas de Transporte/metabolismo , Movimento Celular , Transformação Celular Neoplásica/metabolismo , Células Cultivadas , Vasos Coronários/patologia , Citocinas/metabolismo , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Membro Posterior/irrigação sanguínea , Membro Posterior/patologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Masculino , Camundongos , Camundongos Nus , Camundongos SCID , Músculo Esquelético/patologia , Mioblastos/metabolismo , Mioblastos/transplante , Miocárdio/patologia , Miócitos de Músculo Liso/fisiologia , Neovascularização Fisiológica , Fragmentos de Peptídeos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...