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1.
Elife ; 122023 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-36622753

RESUMEN

Chondrosarcomas are primary cancers of cartilaginous tissue and capable of alteration to highly aggressive, metastatic, and treatment-refractory states, leading to a poor prognosis with a five-year survival rate at 11 months for dedifferentiated subtype. At present, the surgical resection of chondrosarcoma is the only effective treatment, and no other treatment options including targeted therapies, conventional chemotherapies, or immunotherapies are available for these patients. Here, we identify a signal pathway way involving EZH2/SULF1/cMET axis that contributes to malignancy of chondrosarcoma and provides a potential therapeutic option for the disease. A non-biased chromatin immunoprecipitation sequence, cDNA microarray analysis, and validation of chondrosarcoma cell lines identified sulfatase 1 (SULF1) as the top EZH2-targeted gene to regulate chondrosarcoma progression. Overexpressed EZH2 resulted in downregulation of SULF1 in chondrosarcoma cell lines, which in turn activated cMET pathway. Pharmaceutical inhibition of cMET or genetically silenced cMET pathway significantly retards the chondrosarcoma growth and extends mice survival. The regulation of EZH2/SULF1/cMET axis were further validated in patient samples with chondrosarcoma. The results not only established a signal pathway promoting malignancy of chondrosarcoma but also provided a therapeutic potential for further development of effective target therapy to treat chondrosarcoma.


Asunto(s)
Neoplasias Óseas , Condrosarcoma , Proteína Potenciadora del Homólogo Zeste 2 , Sulfotransferasas , Animales , Ratones , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Cartílago/patología , Condrosarcoma/genética , Condrosarcoma/metabolismo , Condrosarcoma/patología , Proteínas Tirosina Quinasas Receptoras/metabolismo , Transducción de Señal , Sulfotransferasas/genética , Humanos , Proteína Potenciadora del Homólogo Zeste 2/genética
2.
BMC Musculoskelet Disord ; 22(1): 572, 2021 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-34162365

RESUMEN

BACKGROUND: The hyaluronic acid (HA) injections are widely used in knee osteoarthritis (OA) patients. We conducted the study comparing the efficacy and safety of single injection of Crosslinked Hyaluronic Acid Platform Hyaluronan (CHAP-HA) with 3-injection of linear hyaluronan in knee OA patients. METHODS: This was a randomized two-arms, evaluator-blinded, controlled, single-center study. Participants with knee OA received single CHAP-HA or three-injection of linear-HA. The 140 patients aged 35-85 years with radiographically confirmed knee OA were enrolled. At week 4, 12, 26, 39, and 52, visual analog scale (VAS) pain score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, timed up and go (TUG) and subject's adverse events (AE) of these 2 groups were recorded. Primary outcome of the differences of VAS pain score at week 26 between groups was analyzed with analysis of covariance (ANCOVA). At week 52, those who met the inclusion criteria could receive a CHAP-HA injection and being followed-up for the adverse events for 4 weeks. RESULTS: The trial was conducted from September 2015 to April 2017. A total 140 subjects were available for analysis (71 in the CHAP-HA group and 69 in the linear-HA group). At 26th week, there were significant more improvements in VAS pain scores in CHAP-HA compared with linear-HA. Both CHAP-HA and linear-HA showed significant improvements in the VAS pain score at week 26 compared with the baseline, and the occurrence of adverse events during the study period showed no between-group difference. In subjects with KL = 2, both groups showed significant improvements in VAS pain scores within 26 weeks. In patients with KL = 3, only CHAP-HA group showed significant improvement in VAS pain from 4 to 39 weeks. No unexpected or severe AEs were reported. CONCLUSIONS: A single injection of CHAP-HA may be safe and more effective for 26 weeks in patients with knee OA by comparing to linear-HA; moreover, the pain relief effect of CHAP-HA may remain until 52 weeks. For patients with more severe OA, CHAP-HA was demonstrated to be more preferable to relieve OA pain. Furthermore, repeat treatment of CHAP-HA or using CHAP-HA after a three-injection HA was proved to be safe. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03643588 . Date: August 23, 2018 (retrospectively registered). LEVEL OF EVIDENCE: Therapeutic Level I.


Asunto(s)
Ácido Hialurónico , Osteoartritis de la Rodilla , Estudios de Seguimiento , Humanos , Ácido Hialurónico/efectos adversos , Inyecciones Intraarticulares , Ontario , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/tratamiento farmacológico , Dolor , Estudios Prospectivos , Resultado del Tratamiento
3.
Phytomedicine ; 53: 1-8, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30668389

RESUMEN

BACKGROUND: Injection of exogenous hyaluronic acid (HA) into the joint capsule improves symptoms of early stage osteoarthritis (OA). However, reactive oxygen species degrade HA into small oligosaccharides that can elicit pro-inflammatory responses. Likewise, disturbance of the antioxidant enzyme system and generation of oxidative stress by pro-inflammatory cytokines worsen knee OA. Accordingly, we proposed the use of aucubin, an antioxidant and anti-inflammatory compound, as a versatile adjuvant to HA for treating OA. METHODS: Primary human chondrocytes were cultured in media supplemented with aucubin in a series of concentrations (0, 0.01, 0.1, 1, and 10 µg/ml) to study dose-dependent toxicity. We then evaluated the therapeutic effects of HA (100 µg/ml) supplemented with aucubin (10 µg/ml) on interleukin-1 beta (IL-1ß, 10 ng/ml)-stimulated chondrocytes. RESULTS: The use of aucubin did not change cell viability or alter lactate dehydrogenase release to normal chondrocytes. Although the proliferation and sulfated glycosaminoglycan production were not affected, aucubin partially restored the hypertrophic transformation of chondrocytes. Relative to treatment with HA or aucubin alone, real-time PCR revealed that aucubin-supplemented HA down-regulated the mRNA levels of tumor necrosis factor-alpha (TNF-α), corrected collagen type 1 and aggrecan, and up-regulated tissue inhibitor of metalloproteinase 1. Moreover, ELISA testing also showed a reduced TNF-α production. Although superoxide dismutases activity was still distributed, aucubin restored total antioxidant capacity of IL-1ß-stimulated chondrocytes. Western blotting further showed that aucubin inhibited cyclooxygenase-2 and regulated the nuclear factor (erythroid-derived 2)-like 2 pathway. CONCLUSION: Aucubin can enhance the anti-catabolic and anti-inflammatory effects of HA on OA chondrocytes.


Asunto(s)
Condrocitos/efectos de los fármacos , Ácido Hialurónico/farmacología , Glucósidos Iridoides/farmacología , Osteoartritis de la Rodilla/patología , Antioxidantes/farmacología , Cartílago Articular/patología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Condrocitos/metabolismo , Condrocitos/patología , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Ciclooxigenasa 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Glicosaminoglicanos/metabolismo , Humanos , Interleucina-1beta/farmacología , Glucósidos Iridoides/administración & dosificación , Factor de Necrosis Tumoral alfa/genética
4.
J Biomed Mater Res B Appl Biomater ; 106(5): 1809-1817, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-28914997

RESUMEN

Proinflammatory cytokines and reactive oxygen species (ROS) are known to be involved in the initiation and progression of osteoarthritis (OA). New evidence clarifying the correlation between ROS and inflammation has indicated that oxidative stress can up-regulate inflammatory cytokines. l-Ascorbic acid (AA), an antioxidant, has been shown to have anti-inflammatory effects and improve matrix deposition in chondrocytes. The purpose of this study was to examine the effects of hyaluronic acid (HA; 100 µg/mL) supplemented with AA (50 µg/mL) on human normal and interleukin-1 beta-stimulated (IL-1ß, 10 ng/mL) chondrocytes. HA, AA, and HA + AA treatment did not change cell morphology, viability, proliferation, and glycosaminoglycan production in normal chondrocytes. HA, AA, and HA + AA, by contrast, partially restored viability and morphology of hypertrophic chondrocytes, and HA and HA + AA further decreased the cytotoxicity of IL-1ß. Real-time PCR revealed that AA and HA + AA had no substantial effects on unstimulated chondrocytes, except for down-regulation of matrix metalloproteinase (MMP)-9 mRNA levels. For IL-1ß-stimulated chondrocytes, significant down-regulation of IL-1ß, tumor necrosis factor-alpha (TNF-α), MMP-3, and MMP-9 mRNA expression was found when cells were cultured in HA-supplemented media. Moreover, HA + AA supplementation further significantly decreased MMP-3 and MMP-9 mRNA expression. The protein production of MMP-3 was decreased, with a significant difference between the HA + AA group and HA group. The antioxidant capacity and superoxide dismutases activity were also partially restored in stimulated chondrocytes. HA supplemented with AA modulates MMPs expression and antioxidant fuction in chondrocytes. AA may enhance the anticatabolic effects of HA on OA chondrocytes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1809-1817, 2018.


Asunto(s)
Ácido Ascórbico/farmacología , Condrocitos/enzimología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Ácido Hialurónico/farmacología , Metaloproteinasa 3 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/biosíntesis , Osteoartritis/metabolismo , Anciano , Anciano de 80 o más Años , Antioxidantes/farmacología , Ácido Ascórbico/agonistas , Condrocitos/patología , Sinergismo Farmacológico , Femenino , Humanos , Ácido Hialurónico/agonistas , Masculino , Persona de Mediana Edad , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Factor de Necrosis Tumoral alfa/biosíntesis
5.
J Knee Surg ; 31(4): 302-305, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28599325

RESUMEN

A reliable method of measuring knee alignment is critical in the preoperative planning of high tibial osteotomy (HTO). This radiological study, based on the measurements of the mechanical and anatomical axes of the lower limb, aimed to determine which method would be more reliable and reproducible. From 2004 to 2013, 50 consecutive patients (50 knees) with medial gonarthrosis were treated with valgus-producing HTO. Four independent investigators assessed preoperative standing lower limb radiography (including hip, knee, and ankle joints) to measure both anatomical and mechanical axes. We defined a response as a difference in the angle measured by the same investigator using the same method. The covariates were the investigators and methods. To account for both inter- and intraobserver variabilities, all data were evaluated using a generalized estimating equation model. The results revealed that the effect of the investigators was not statistically significant; however, the effect of the measurement method was highly significant (p < 0.0001). The estimated coefficient of the anatomical axis method was negative, indicating that the reproducibility of the anatomical axis method was better than that of the mechanical axis.


Asunto(s)
Desviación Ósea/diagnóstico por imagen , Enfermedades de los Cartílagos/cirugía , Articulación de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteotomía/métodos , Tibia/diagnóstico por imagen , Articulación del Tobillo/diagnóstico por imagen , Desviación Ósea/prevención & control , Enfermedades de los Cartílagos/diagnóstico por imagen , Articulación de la Cadera/diagnóstico por imagen , Humanos , Articulación de la Rodilla/cirugía , Extremidad Inferior/diagnóstico por imagen , Variaciones Dependientes del Observador , Osteoartritis de la Rodilla/cirugía , Postura , Cuidados Preoperatorios , Reproducibilidad de los Resultados , Tibia/cirugía
6.
Chin J Physiol ; 59(4): 191-201, 2016 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-27426258

RESUMEN

The incidence of osteoporosis has increased among the elderly population. Establishing a model of bone remodeling for screening new drugs is critical to identify safe and effective treatments for osteoporosis. In this study, we established a platform to investigate the therapeutic effects of collagenous peptides extracted from scales of two kinds of fish, namely, sparidae and chanos. These peptides were prepared using seven concentrations of collagenous peptide: 100, 80, 60, 40, 20, 10 and 1 mg/ml. Experimental results indicated that collagenous peptides promoted the proliferation of osteoblasts and inhibited the proliferation of mature osteoclasts; the effective concentration of collagenous peptide-sparidae was 10 mg/ml and that of collagenous peptide-chanos was 40 mg/ml. These findings demonstrate that, to a certain extent, collagenous peptides extracted from fish scales can be used to prevent osteoporosis to assist bone remodeling.


Asunto(s)
Colágeno/uso terapéutico , Proteínas de Peces/uso terapéutico , Osteoblastos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoporosis/prevención & control , Animales , Resorción Ósea/prevención & control , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colágeno/farmacología , Evaluación Preclínica de Medicamentos , Proteínas de Peces/farmacología , Humanos , Perciformes
7.
Med Eng Phys ; 38(10): 1070-5, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27423702

RESUMEN

Open reduction internal fixation technique has been generally accepted for treatment of midshaft clavicle fractures. Both superior and anterior clavicle plates have been reported in clinical or biomechanical researches, while presently the spiral clavicle plate design has been introduced improved biomechanical behavior over conventional designs. In order to objectively realize the multi-directional biomechanical performances among the three geometries for clavicle plate designs, a current conceptual finite element study has been conducted with identical cross-sectional features for clavicle plates. The conceptual superior, anterior, and spiral clavicle plate models were constructed for virtual reduction and fixation to an OTA 15-B1.3 midshaft transverse fracture of clavicle. Mechanical load cases including cantilever bending, axial compression, inferior bending, and axial torsion have been applied for confirming the multi-directional structural stability and implant safety in biomechanical perspective. Results revealed that the anterior clavicle plate model represented lowest plate stress under all loading cases. The superior clavicle plate model showed greater axial compressive stiffness, while the anterior clavicle plate model performed greater rigidity under cantilever bending load. Three model represented similar structural stiffness under axial torsion. Played as a transition structure between superior and anterior clavicle plate, the spiral clavicle plate model revealed comparable results with acceptable multi-directional biomechanical behavior. The concept of spiral clavicle plate design is worth considering in practical application in clinics. Implant safety should be further investigated by evidences in future mechanical tests and clinical observations.


Asunto(s)
Clavícula/lesiones , Análisis de Elementos Finitos , Fracturas Óseas , Fenómenos Mecánicos , Anciano , Fenómenos Biomecánicos , Placas Óseas , Tornillos Óseos , Clavícula/diagnóstico por imagen , Clavícula/cirugía , Humanos , Masculino , Tomografía Computarizada por Rayos X
8.
J Biomed Mater Res A ; 104(8): 2071-9, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27027581

RESUMEN

Intra-articular injection of hyaluronic acid (HA) has been widely accepted for the treatment of osteoarthritis (OA) in early stage. l-Glutathione (GSH), an antioxidant, has an anti-inflammatory effect on protecting cells from reactive oxygen species and reactive nitrogen species (ROS/RNS). In this study, the therapeutic effects of HA (0.1%) supplemented with GSH (0, 5, 10, and 20% in weight ratios to HA) on human fibroblast-like synoviocytes (FLSs) were evaluated. The results showed that cell morphology and glycosaminoglycan production of FLSs were not changed under treatments. However, the addition of HA + 20% GSH significantly decreased cell survival (p < 0.001) relative to other groups. Relative to un-stimulated FLSs, interleukin-1 beta (IL-1ß) stimulation significantly decreased the total antioxidant capacity (p < 0.001) of cells. The antioxidant capacity was restored and the intracellular ROS/RNS was decreased in HA or HA + GSH-treated FLSs. Real-time PCR analysis revealed the mRNA levels of IL-1ß, tumor necrosis factor-alpha, and matrix metalloproteinase-3 were down-regulated significantly (all p < 0.05) when FLSs cultured in HA or HA + GSH. IL-6 mRNA expressions were down-regulated significantly in HA and HA + 5% GSH groups (both p < 0.05) but up-regulated when HA supplemented with 10% and 20% GSH (both p < 0.01). In addition, the protein levels of IL-1ß were further decreased with significant differences (both p < 0.05) in the HA + 10% GSH and HA + 20% GSH groups when compared to FLSs cultured in normal medium. In conclusion, HA supplemented with GSH improves antioxidant capacity and modulates pro-inflammatory cytokines expressions in FLSs. GSH has the potential to augment the effect of viscosupplementation using HA on OA patients. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2071-2079, 2016.


Asunto(s)
Antioxidantes/farmacología , Citocinas/metabolismo , Fibroblastos/citología , Glutatión/farmacología , Ácido Hialurónico/farmacología , Mediadores de Inflamación/metabolismo , Sinoviocitos/citología , Anciano , Forma de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/genética , Femenino , Glicosaminoglicanos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/metabolismo , Osteoartritis/patología , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Sinoviocitos/efectos de los fármacos
9.
Biomed Res Int ; 2015: 780451, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26273644

RESUMEN

This study evaluates the safety and effectiveness of computed tomography- (CT-) assisted endoscopic surgery in the treatment of infectious spondylodiscitis of the thoracic and upper lumbar spine in immunocompromised patients. From October 2006 to March 2014, a total of 41 patients with infectious spondylodiscitis underwent percutaneous endoscopic surgery under local anesthesia, and 13 lesions from 13 patients on the thoracic or upper lumbar spine were selected for evaluation. A CT-guided catheter was placed before percutaneous endoscopic surgery as a guide to avoid injury to visceral organs, major vessels, and the spinal cord. All 13 patients had quick pain relief after endoscopic surgery without complications. The bacterial culture rate was 77%. Inflammatory parameters returned to normal after adequate antibiotic treatment. Postoperative radiographs showed no significant kyphotic deformity when compared with preoperative films. As of the last follow-up visit, no recurrent infections were noted. Traditional transthoracic or diaphragmatic surgery with or without posterior instrumentation is associated with high rates of morbidity and mortality, especially in elderly patients, patients with multiple comorbidities, or immunocompromised patients. Percutaneous endoscopic surgery assisted by a CT-guided catheter provides a safe and effective alternative treatment for infectious spondylodiscitis of the thoracic and upper lumbar spine.


Asunto(s)
Discitis/inmunología , Discitis/cirugía , Endoscopía/métodos , Huésped Inmunocomprometido/inmunología , Vértebras Lumbares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/patología , Infecciones Bacterianas/cirugía , Discitis/patología , Endoscopía/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Cirugía Asistida por Computador/métodos
10.
J Trauma Acute Care Surg ; 74(1): 317-21, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23505668

RESUMEN

BACKGROUND: Distal radius fracture is recognized as an osteoporosis-related fracture in aged population. If another osteoporosis-related fracture occurs in a short period, it represents a prolonged hospitalization and a considerable economic burden to the society.We evaluated the relationship between distal radius fracture and subsequent hip fracture within 1 year, especially in the critical time and age. METHODS: We identified newly diagnosed distal radius fracture patients in 2000 to 2006 as an exposed cohort (N = 9,986). A comparison cohort (N = 81,227) was randomly selected from patients without distal radius fracture in the same year of exposed cohort. The subjects were followed up for 1 year since the recruited date.We compared the sociodemographic factors between two cohorts.Furthermore, the time interval following the previous distal radial fracture and the incidence of subsequent hip fracture was studied in detail. RESULTS: The incidence of hip fracture within 1 year increased with age in both cohorts. The risk was 5.67 times (84.6 vs. 14.9 per 10,000 person-years) greater in the distal radial fracture cohort than in the comparison cohort. The multivariate Cox proportional hazard regression analyses showed the hazard ratios of hip fracture in relation to distal radial fracture was 3.45 (95% confidence interval = 2.59-4.61). The highest incidence was within the first month after distal radial fracture, 17-fold higher than the comparison cohort (17.9 vs. 1.05 per 10,000). Among comorbidities, age 9 60 years was also a significant factor associated with hip fracture (hazard ratio = 8.67, 95% confidence interval = 4.51-16.7). CONCLUSIONS: Patients with distal radius fracture and age 960 years will significantly increase the incidence of subsequent hip fracture, especially within the first month. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level II.


Asunto(s)
Fracturas de Cadera/complicaciones , Fracturas Osteoporóticas , Fracturas del Radio/complicaciones , Adulto , Femenino , Fracturas de Cadera/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo
11.
J Shoulder Elbow Surg ; 22(7): 932-9, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23312816

RESUMEN

BACKGROUND: This study aims to clarify the effect of various designs of reverse shoulder prosthesis (RSP) on stress variation of its glenoid component using 2-dimensional (2D) finite element analysis (FEA). This FEA study provides future reference for the optimal design of glenoid component of RSP. MATERIALS AND METHODS: In this study, a 2D finite element (FE) model of human shoulder with implementation of RSP was developed by commercial FE software. The proper material properties were adopted in our model. Various design factors were simulated and all the mechanical profile data were investigated by FEA. RESULTS: Both distal placement and increased lateral offset of glenosphere induce higher stress over glenoid-baseplate junction. Increased thickness of graft, inferiorly tilting of the baseplate, and adoption of BIO-RSA (bony increased-offset reverse shoulder arthroplasty) incur higher stresses over glenoid screws. The inferior screw attains more stress than superior screw. Maximum stress occurs at the base of inferior screw. CONCLUSION: Increased eccentric offset and lateral offset of glenosphere, although being able to reduce notching, may pay the penalty of significant stress concentration over glenoid and its subsequent loosening. Maximum stress occurs at the base of inferior screw elucidate the direct contact failure mode at the middle of inferior screw. This study provides an alternative tool for the optimal design of glenoid component of RSP in the future.


Asunto(s)
Artroplastia de Reemplazo/métodos , Análisis de Elementos Finitos , Prótesis Articulares , Articulación del Hombro/cirugía , Estrés Mecánico , Artroplastia de Reemplazo/instrumentación , Fenómenos Biomecánicos , Placas Óseas , Tornillos Óseos , Humanos , Modelos Anatómicos , Diseño de Prótesis , Sensibilidad y Especificidad
12.
BMC Musculoskelet Disord ; 12: 221, 2011 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-21978211

RESUMEN

BACKGROUND: The efficacy and tolerability of 500-730 kDa sodium hyaluronate (Hyalgan®) for treatment of osteoarthritis (OA) pain has been established in clinical trials, but few data are available in the Asian population. We conducted a randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and tolerability of this preparation in a Taiwanese population. METHODS: Two hundred patients with mild to moderate OA of the knee were randomized to receive five weekly intra-articular injections of sodium hyaluronate or placebo. The primary efficacy outcome was the change from baseline to Week 25 in patients' evaluation of pain using a 100-mm visual analog scale (VAS) during the 50-foot walking test. Additional outcomes included Western Ontario and McMaster Universities (WOMAC) scores, time on the 50-foot walking test, patient's and investigator's subjective assessment of effectiveness, acetaminophen consumption, and the amounts of synovial fluid. RESULTS: The Hyalgan® treatment group showed a significantly greater improvement from baseline to Week 25 in VAS pain on the 50-foot walking test than the placebo group (p = 0.0020). The Hyalgan® group revealed significant improvements from baseline to week 25 in WOMAC pain and function score than the placebo group (p = 0.005 and 0.0038, respectively) Other outcomes, such as time on the 50-foot walking test and subjective assessment of effectiveness, did not show any significant difference between groups. Both groups were safe and well tolerated. CONCLUSIONS: The present study suggests that five weekly intra-articular injections of sodium hyaluronate are well tolerated, can provide sustained relief of pain, and can improve function in Asian patients with osteoarthritis of the knee. TRIAL REGISTRATION: Therapeutic study, Level I-1a (randomized controlled trial with a significant difference).


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Ácido Hialurónico/uso terapéutico , Osteoartritis de la Rodilla/tratamiento farmacológico , Adyuvantes Inmunológicos/administración & dosificación , Anciano , Pueblo Asiatico , Método Doble Ciego , Prueba de Esfuerzo , Femenino , Estado de Salud , Humanos , Ácido Hialurónico/administración & dosificación , Inyecciones Intraarticulares , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/etnología , Osteoartritis de la Rodilla/fisiopatología , Dimensión del Dolor , Recuperación de la Función , Taiwán/epidemiología , Resultado del Tratamiento , Caminata
13.
J Orthop Res ; 29(4): 495-500, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20957732

RESUMEN

Progression to osteoarthritis (OA) is a frequent sequela of severe articular fracture, particularly when weight-bearing joints are involved. Prevention from post-traumatic OA remains a challenge. Hyaluronan (HA) therapy is reported to represent a safe and effective treatment for patients with OA and rheumatoid arthritis. However, the capacity of HA to prevent the occurrence of osteoarthritic changes in fractured joints has not been demonstrated. The present study was undertaken to examine the effects of HA on expression of six OA-related proteins in fibroblast-like synoviocytes (FLS) from 10 patients with tibia plateau fracture. OA-related factors were quantified using a sandwich enzyme-linked immunosorbent assay. Regardless of induction of the FLS with interleukin (IL)-1ß, HA was found to down-regulate expression of catabolic factors (IL-1ß, matrix metalloproteinase-3, and tumor necrosis factor-α) and to up-regulate production of anti-catabolic factors (tissue inhibitors of metalloproteinase-1 and metalloproteinase-2). HA also enhanced expression of IL-10, an anti-inflammatory cytokine, in FLS. Our results indicated that HA can promote the expression of both antiinflammatory and structure-protective factors in FLS of patients with tibia plateau fracture.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Ácido Hialurónico/farmacología , Interleucina-10/metabolismo , Membrana Sinovial/efectos de los fármacos , Fracturas de la Tibia/patología , Regulación hacia Arriba/efectos de los fármacos , Adulto , Biomarcadores/metabolismo , Células Cultivadas , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Interleucina-10/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Traumatismos de la Rodilla , Masculino , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , Persona de Mediana Edad , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Tibia/metabolismo , Tibia/patología , Fracturas de la Tibia/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
14.
J Trauma ; 68(1): 146-52, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20065770

RESUMEN

BACKGROUND: Preventing arthritic change in a joint with an intra-articular fracture remains a challenge, especially in weight-bearing joints. Hyaluronan (HA) has been proven to be effective in relieving joint pain and improving function in chronic osteoarthritis. However, controversy still exists about its potential use in a joint with an intra-articular fracture and about whether this effect is dependent on molecular weight. We analyzed and compared the effects of two different molecular weight HAs on six osteoarthritis-related proteins expressed in fibroblast-like synoviocytes from 12 patients with tibial plateau fracture. METHODS: The interleukin (IL)-1beta-stimulated or IL-1beta-unstimulated fibroblast-like synoviocytes were cultivated with or without treatment by two different molecular weight HAs. The production of these proteins was quantified by using commercially available sandwich enzyme-linked immunosorbent assay. RESULTS: The results revealed that HA with a high molecular weight is more effective in downregulating proinflammatory cytokines such as interleukin-1beta and tumor necrosis factor-alpha. Conversely, HA with a low molecular weight has greater efficacy in upregulating anticatabolic enzymes, such as tissue inhibitor of metalloproteinase-1 and tissue inhibitor of metalloproteinase-2, and in suppressing the catabolic enzyme, matrix metalloproteinase-3, which are thought to be more chondroprotective. CONCLUSIONS: In a knee joint with an intra-articular fracture of the tibial plateau, we posit that high molecular weight HA may have a better anti-inflammatory effect, whereas low molecular weight HA has superior efficacy for chondroprotection.


Asunto(s)
Ácido Hialurónico/farmacología , Osteoartritis de la Rodilla/metabolismo , Membrana Sinovial/metabolismo , Fracturas de la Tibia/metabolismo , Viscosuplementos/farmacología , Adolescente , Adulto , Artroscopía , Células Cultivadas , Humanos , Ácido Hialurónico/administración & dosificación , Inyecciones Intraarticulares , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacología , Fracturas Intraarticulares/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Persona de Mediana Edad , Peso Molecular , Osteoartritis de la Rodilla/etiología , Osteoartritis de la Rodilla/terapia , Membrana Sinovial/citología , Membrana Sinovial/efectos de los fármacos , Fracturas de la Tibia/complicaciones , Fracturas de la Tibia/patología , Lesiones de Menisco Tibial , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Viscosuplementos/administración & dosificación , Adulto Joven
15.
Injury ; 40(3): 231-5, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19121827

RESUMEN

A retrospective study was performed to evaluate the use of an AO reconstruction plate in open reduction and internal fixation for non-union of the mid-shaft clavicle, examining the relationship between the position of the scapula and final functional results and whether perioperative variables such as clavicular reconstruction ratio and period of non-union influence the position of the scapula. From January 1998 to January 2005, data on 21 people with symptomatic non-union of the mid-shaft clavicle were collected; 17 non-unions were atrophic and 4 were hypertrophic. Initially, treatment was conservative with a figure-of-eight bandage in 19 cases, and cerclage wire fixation in 2 cases. The follow-up period was 65.7 (24-108) months. Outcome analyses included standard clinical follow-up, plain radiography, the Constant-Murley scoring and subjective assessment. All non-unions united well in 13.6 (11-27) weeks. All patients were satisfied with their surgical results. Greater age and longer period of non-union resulted in a larger amount of scapular malposition, which related to poor functional results.


Asunto(s)
Placas Óseas , Clavícula/lesiones , Fijación Interna de Fracturas/métodos , Fracturas no Consolidadas/cirugía , Escápula/lesiones , Adolescente , Adulto , Anciano , Clavícula/diagnóstico por imagen , Femenino , Curación de Fractura , Fracturas no Consolidadas/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Radiografía , Rango del Movimiento Articular/fisiología , Estudios Retrospectivos , Escápula/diagnóstico por imagen , Adulto Joven
16.
J Chin Med Assoc ; 69(8): 372-6, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16970273

RESUMEN

BACKGROUND: The purpose of this prospective study was to identify if F-18-fluorodeoxy-D-glucose positron emission tomography (F-18-FDG PET) was a reliable noninvasive surrogate of histologic response in determining the efficacy of neoadjuvant chemotherapy before surgical resection in primary osteosarcoma. METHODS: Between January 2003 and December 2003, 10 patients with primary osteosarcomas were examined using F-18-FDG PET before neoadjuvant chemotherapy and surgery. The mean age at the time of first intervention was 19 years (range, 4-47 years). Positive prognostic significance was defined as more than 90% tumor necrosis response following neoadjuvant chemotherapy. The parameters of FDG uptake were correlated with histologic findings. The intraclass correlation coefficient was used to validate the tumor necrosis rates determined by PET and histology. RESULTS: The tumor necrosis rate determined by PET was comparable with that determined histologically. The mean standardized uptake value before and following neoadjuvant chemotherapy were 8.2 and 4.4, respectively. The average tumor necrosis rate determined by PET was 22%. However, the mean tumor necrosis rate determined histologically was 54.5%. According to the intraclass correlation coefficient models, the intraclass correlation coefficient equaled O. The relationship of tumor necrosis rates determined by F-18-FDG PET and histology seems to be statistically insignificant. CONCLUSION: In this preliminary study, FDG PET did not seem to be a promising tool for evaluating the response of primary osteosarcoma to neoadjuvant chemotherapy.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patología , Fluorodesoxiglucosa F18 , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/patología , Tomografía de Emisión de Positrones , Adolescente , Adulto , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Necrosis , Estudios Prospectivos
17.
J Chin Med Assoc ; 68(10): 474-8, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16265862

RESUMEN

BACKGROUND: A retrospective group study was done to evaluate the effect of the small AO external fixator in the management of acute intra-articular fractures of the distal radius. METHODS: Between January 1995 and December 1996, 70 consecutive patients with articular fractures of the distal radius were treated by closed reduction and external fixation with small AO external fixators. The mean age at the time of surgery was 58.9 years (range, 14-87 years). There were 58 Colles' Barton's fractures and 12 Smith's Barton's fractures. The follow-up period was 104 months (range, 92-118 months). RESULTS: All fractures united in a mean of 5.8 weeks (range, 4-10 weeks). At the final follow-up, the average range of motion was 56.3 +/- 11.6 degrees in flexion, 58.6 +/- 10.7 degrees in extension, 21.5 +/- 4.2 degrees in ulnar deviation, 9.1 +/- 2.9 degrees in radial deviation, 71.5 +/- 8.5 degrees in pronation, and 67.3 +/- 9.2 degrees in supination. Compared with the normal side, the average grip force was 87 +/- 6%. The overall clinical and functional outcomes, according to the scoring system of Gartland and Werley, showed that 22 patients (31.4%) had excellent results, 36 (51.4%) had good results, 9 (12.9%) had fair results, and 3 (4.3%) had poor results. CONCLUSION: Closed reduction and external fixation with the small AO external fixator is useful and effective in the management of displaced comminuted articular fractures of the distal radius.


Asunto(s)
Fijadores Externos , Fracturas del Radio/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
18.
J Chin Med Assoc ; 68(9): 425-30, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16187599

RESUMEN

BACKGROUND: A retrospective cohort study was conducted to evaluate the outcomes of massive allograft arthrodesis in the management of high-grade osteosarcoma around the knee. METHODS: The results of 19 patients with high-grade osteosarcoma around the knee, which was treated by wide resection and reconstruction using allograft arthrodesis, were evaluated for a mean length of 7.3 years (range, 3-13 years). The mean age at the time of surgery was 13.3 years (range, 6-27 years). According to the Musculoskeletal Tumor Society staging system, 17 patients were stage IIB and 2 were stage IIIB at presentation. Evaluations were based on the oncologic results, non-oncologic results and complications. Functional evaluation was performed with the Enneking functional evaluation form. RESULTS: Four patients (21.1%) died of their disease; 3 (15.8%) are alive with disease; and 12 (63.2%) are free of disease. Four patients (21.1%) had local recurrence of their tumor at a mean of 23 months postoperatively (range, 9-44 months). The mean time to union of the metaphyseal junction was 24.7 weeks (range, 16-30 weeks) and the diaphyseal junction was 47 weeks (range, 24-78 weeks). The overall complication rate was 31.6%, including 2 (10.5%) infections, 3 (15.8%) allograft fractures, and 1 (5.3%) nonunion. Our mean final functional result was 65%. CONCLUSION: Due to the high rate of complications in this study, we conclude that allograft arthrodesis should be left as a salvage or "back-up" reconstructive procedure after resection of osteosarcoma around the knee, unless there are special indications for this procedure. We found allograft fracture to be the most common complication.


Asunto(s)
Artrodesis/métodos , Neoplasias Óseas/cirugía , Trasplante Óseo , Articulación de la Rodilla/cirugía , Osteosarcoma/cirugía , Adolescente , Adulto , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Estudios Retrospectivos , Trasplante Homólogo
19.
Clin Orthop Relat Res ; (432): 188-95, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15738821

RESUMEN

A prospective group study was done to clarify whether perioperative variables such as preoperative and postoperative tibiofemoral angles influence the survivorship of proximal tibia osteotomy as measured by conversion to arthroplasty and patient dissatisfaction. The results of 93 proximal tibial osteotomies in 82 consecutive patients with medial compartment osteoarthrosis were followed up for a mean of 10.9 years. All data were analyzed by the Kaplan-Meier survivorship method and the multivariate Cox proportional hazards model. Only the preoperative tibiofemoral angle was a predictor of conversion to arthroplasty and patient dissatisfaction. The ideal prognostic cutoff angle was 9 degrees or less varus. Increasing the preoperative varus alignment 1 degrees would result in a 1.2 (95% confidence intervals, 1.02-1.50) times higher risk of conversion to a total knee arthroplasty and a 1.5 (95% confidence intervals, 1.27-1.76) times higher chance of patient dissatisfaction. Factors such as age, gender, body mass index, Ahlback's classification, and postoperative tibiofemoral angle were not significant. We think that proximal tibial osteotomy should be considered for patients with medial compartment osteoarthrosis and a preoperative varus alignment of 9 degrees or less, whereas arthroplasty is a more suitable alternative for patients with preoperative varus alignment greater than 9 degrees.


Asunto(s)
Fémur/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Osteotomía , Tibia/diagnóstico por imagen , Tibia/cirugía , Adulto , Anciano , Artroplastia de Reemplazo de Rodilla , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud , Satisfacción del Paciente , Pronóstico , Estudios Prospectivos , Radiografía
20.
J Trauma ; 58(1): 62-9, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15674152

RESUMEN

BACKGROUND: We would like to define the results of treatment of open reduction and internal fixation in elderly patients with severe fractures of the distal humerus. METHODS: Between 1988 and 1998, 19 consecutive aged patients (older than 65 years old) with displaced comminuted articular fractures of the distal humerus were treated by open reduction and internal fixation with AO reconstruction plate. The age at the time of injury was 71.9 (65-79) years old. According to the AO classification, 15 patients had type C2 and four had type C3 injury. No patient had inflammatory arthritis of the elbow. The period of follow up is 97.2 (60-174) months. RESULTS: All fractures united with union time of 14.6 (11-20) weeks. No implant failure was found. In final follow up, the average flexion contracture was 16.8 degrees with a range of 0-40 degrees , the average active flexion was 128.4 degrees with a range of 115-140 degrees , the average pronation was 80 degrees with a range of 60-90 degrees , and the average supination was 78 degrees with a range of 60-90 degrees . According to the elbow motion classification of Cassebaum, eight (42.1%) patients were graded as very good elbow motion, eight (42.1%) as good, three (15.8%) as fair, and none as poor. The functional results showed that 15 (79%) patients had excellent results, four (21%) had good results, and none had fair or poor results, according to Mayo elbow performance score. The radiographic evaluation in final follow up showed that four patients (21%) had no osteoarthritic (OA) change, 11 (58%) had grade 1 OA, four (21%) had grade 2 OA, and none had grade 3 OA (the scale of Knirk and Jupiter). Fifteen (79%) patients reported no pain and four (21%) had mild pain. All patients were satisfied with their results. However, There were two early post-operative complications, including one (5.3%) superficial wound infection and one (5.3%) iatrogenic ulnar nerve injury. CONCLUSIONS: Open reduction and internal fixation with appropriate surgical technique is effective in the treatment of displaced fractures of the distal humerus in elderly patients.


Asunto(s)
Fijación Interna de Fracturas , Fracturas Conminutas/cirugía , Fracturas del Húmero/cirugía , Anciano , Placas Óseas , Hilos Ortopédicos , Femenino , Fracturas Conminutas/diagnóstico por imagen , Humanos , Fracturas del Húmero/diagnóstico por imagen , Masculino , Osteoartritis/epidemiología , Radiografía , Rango del Movimiento Articular , Resultado del Tratamiento
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