RESUMEN
OBJECTIVES: The Osteoarthritis Questionnaire (OA-Quest) is a new measure of individual burden of osteoarthritis, composing seven brief (4-11 items; total 42 items), independent scales. This study describes the psychometric evaluation of the OA-Quest. Specifically, temporal stability, convergent and discriminant validity, and responsiveness of the OA-Quest to joint replacement surgery were examined. STUDY DESIGN AND SETTING: Participants were drawn from rheumatology (n = 62), orthopedic (n = 90), and community (n = 175) settings. Temporal stability of the OA-Quest was evaluated over a 2-week period and was assessed with intraclass correlation coefficients. Responsiveness was assessed with standardized effect sizes and paired samples t-tests. Convergent and discriminant validity was assessed with a multitrait multimethod confirmatory factor analysis (MTMM CFA). RESULTS: The OA-Quest scales had high temporal stability, with intraclass correlation coefficients between 0.75 (lost productivity) and 0.94 (physical limitations) and showed improvements of expected magnitude and direction 3 months after joint replacement surgery, supporting their responsiveness. MTMM CFA supported the convergent and discriminant validity of the OA-Quest, demonstrated by adequate model fit (χ2 = 483.54, df = 184, P < 0.001, comparative fit index = 0.95, Tucker-Lewis index = 0.93, root mean square error of approximation = 0.07, standardized root mean square residual = 0.06) and factor loadings of the expected magnitude and direction. CONCLUSION: The OA-Quest has strong evidence of temporal stability, construct validity, and is responsive to change following joint replacement surgery.
Asunto(s)
Artroplastia de Reemplazo/estadística & datos numéricos , Encuestas Epidemiológicas/estadística & datos numéricos , Osteoartritis/cirugía , Medición de Resultados Informados por el Paciente , Adulto , Anciano , Anciano de 80 o más Años , Análisis Discriminante , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Psicometría , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
Human tissue and cell-based therapeutic interventions provide efficacious alternative treatment where traditional drugs or medical devices have proved unsatisfactory. Yet human tissue and cell-based products (HTC/P) still present a series of challenges regarding their safety and efficacy. By reviewing the history of development and current regulatory standards and observing activities related to the manufacture of HTC/P, we have described the common characteristics of HTC/P, including the risk of pathogen transmission, transportation methods of human tissues, quality control in HTC/P manufacturing, and the concern of ancillary materials. The ethical issues of cadaveric donation and clinical trial standards for HTC/P have also been discussed. Overall, we have provided a general standard, which articulates the essential requirements on the safety and efficacy of HTC/P.
Asunto(s)
Trasplante de Células , Trasplante de Tejidos , Trasplante de Células/efectos adversos , Trasplante de Células/normas , Enfermedades Transmisibles/etiología , Humanos , Seguridad , Trasplante de Tejidos/efectos adversos , Trasplante de Tejidos/normasRESUMEN
SHP-2 (Src homology phosphatase type-2) is essential for haematopoietic skeletal and vascular development. Thus the identification of its binding partners is critically important. In the present study, we describe a unique monoclonal antibody, WM78, which interacts with PZR, a SHP-2 binding partner. Furthermore, we identify two novel isoforms of PZR, PZRa and PZRb, derived by differential splicing from a single gene transcription unit on human chromosome 1q24. All are type 1 transmembrane glycoproteins with identical extracellular and transmembrane domains, but differ in their cytoplasmic tails. The PZR intracellular domain contains two SHP-2 binding immunoreceptor tyrosine-based inhibitory motifs (VIY(246)AQL and VVY(263)ADI) which are not present in PZRa and PZRb. Using the WM78 monoclonal antibody, which recognizes the common extracellular domain of the PZR isoforms, we demonstrate that the PZR molecules are expressed on mesenchymal and haematopoietic cells, being present on the majority of CD34(+)CD38(+) and early clonogenic progenitors, and at lower levels on CD34(+)CD38(-) cells and the hierarchically more primitive pre-colony forming units. Interestingly, we show by reverse transcriptase-PCR that the PZR isoforms are differentially expressed in haematopoietic, endothelial and mesenchymal cells. Both PZR and PZRb are present in CD133(+) precursors and endothelial cells, PZRb predominates in mesenchymal and committed myelomonocytic progenitor cells, and all three isoforms occur in erythroid precursor cell lines. Importantly, using SHP-2 mutant (Delta 46-110) and SHP-2 rescue of embryonic fibroblasts stably expressing the PZR isoforms, we demonstrate for the first time that PZR, but not PZRa or PZRb, facilitates fibronectin- dependent migration of cells expressing a competent SHP-2 molecule. These observations will be instrumental in determining the mechanisms whereby PZR isoforms regulate cell motility.