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1.
Neurology ; 102(10): e209395, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38669629

RESUMO

BACKGROUND AND OBJECTIVES: We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia. METHODS: In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm. RESULTS: Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG. DISCUSSION: The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03049956.


Assuntos
Blefaroptose , Diplopia , Miastenia Gravis , Potenciais Evocados Miogênicos Vestibulares , Humanos , Miastenia Gravis/diagnóstico , Miastenia Gravis/fisiopatologia , Miastenia Gravis/complicações , Masculino , Feminino , Diplopia/diagnóstico , Diplopia/fisiopatologia , Diplopia/etiologia , Pessoa de Meia-Idade , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Adulto , Blefaroptose/diagnóstico , Blefaroptose/fisiopatologia , Blefaroptose/etiologia , Idoso , Estudos Prospectivos , Eletromiografia/métodos , Sensibilidade e Especificidade , Músculos Oculomotores/fisiopatologia , Adulto Jovem
2.
Biomaterials ; 35(25): 7180-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24875761

RESUMO

Chemokine-induced stem cell recruitment is a promising strategy for post myocardial infarction treatment. Injection of stromal cell-derived factor 1 (SDF1) has been shown to attract bone marrow-derived progenitor cells (BMPCs) from the blood that have the potential to differentiate into cardiovascular cells, which support angiogenesis, enabling the improvement of myocardial function. SDF1-GPVI bi-specific protein contains a glycoprotein VI (GPVI)-domain that serves as an anchor for collagen type I (Col I) and III, which are exposed in the wall of injured vasculature. In this study, we generated a cytocompatible hydrogel via photo-crosslinking of poly(ethylene glycol) diacrylate that serves as a reservoir for SDF1-GPVI. Controlled and sustained release of SDF1-GPVI was demonstrated over a period of 7 days. Release features were modifiable depending on the degree of the crosslinking density. Functionality of the GPVI-domain was investigated using a GPVI-binding ELISA to Col I. Activity of the SDF1-domain was tested for its CXCR4 binding potential. Preserved functionality of SDF1-GPVI bi-specific protein after photo-crosslinking and controllable release was successfully demonstrated in vitro supporting the implementation of this drug delivery system as a powerful tool for therapeutic protein delivery in the treatment of cardiovascular ischemic disease.


Assuntos
Quimiocina CXCL12/metabolismo , Hidrogéis/química , Infarto do Miocárdio/terapia , Glicoproteínas da Membrana de Plaquetas/metabolismo , Polietilenoglicóis/química , Animais , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Colágeno Tipo I/química , Sistemas de Liberação de Medicamentos/métodos , Células Progenitoras Endoteliais , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Receptores CXCR4/química
3.
Biomaterials ; 33(21): 5259-66, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22521489

RESUMO

Decorin is a structural and functional proteoglycan (PG) residing in the complex network of extracellular matrix (ECM) proteins in many connective tissues. Depending on the protein core and the glycosaminoglycan chain, PGs support cell adhesion, migration, proliferation, differentiation, ECM assembly and growth factor binding. For applications in tissue engineering, it is crucial to develop reliable, ECM-mimicking biomaterials. Electrospinning is a suitable method for creating three-dimensional (3D), fibrillar scaffolds. While there are numerous reports on the electrospinning of proteins including collagen, to date, there are no reports on the electrospinning of PGs. In the following study, we used electrospinning to generate decorin-containing matrices for tracheal tissue engineering applications. The electrospun scaffolds were analyzed using scanning electron microscopy, atomic force microscopy, contact angle measurements and dynamic mechanical analysis. Additionally, we confirmed PG functionality with immunostaining and 1,9-dimethylmethylene blue. To determine cell-matrix-interactions, tracheal cells (hPAECs) were seeded and analyzed using an FOXJ1-antibody. Moreover, interactions of the electrospun scaffolds with immune-mediated mechanisms were analyzed in detail. To conclude, we demonstrated the feasibility of electrospinning of decorin to generate functional 3D scaffolds with low immunogenicity for hPAEC expansion. Our data suggest that these hybrid materials may be suitable as a substrate for tracheal tissue engineering.


Assuntos
Decorina/farmacologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Engenharia Tecidual/métodos , Traqueia/efeitos dos fármacos , Traqueia/fisiologia , Animais , Anticorpos/imunologia , Bovinos , Proliferação de Células/efeitos dos fármacos , Separação Celular , Células Cultivadas , Citocinas/metabolismo , Decorina/imunologia , Decorina/ultraestrutura , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fluoresceínas/metabolismo , Gelatina/farmacologia , Humanos , Imuno-Histoquímica , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Microscopia de Força Atômica , Especificidade de Órgãos/efeitos dos fármacos , Poliésteres/farmacologia , Succinimidas/metabolismo , Sus scrofa , Alicerces Teciduais , Traqueia/citologia
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