Insulin-like growth factor-1 treatment prevents anti-fas antibody-induced apoptosis in endplate chondrocytes

Study Design. In vitro investigation of vertebral endplate chondrocyte apoptosis. Objectives. To determine whether Fas antibody caused apoptosis in endplate chondrocytes, and whether insulin-like growth factor-1 (IGF-1) inhibited this effect. Integrin-ā1 and focal adhesion kinase (FAK) expression in conjunction with apoptosis was also investigated. Summary of Background Data. Binding of Fas antibody to Fas mimics Fas-FasL ligation, which causes apoptosis. IGF-1 has been shown to have anti-apoptotic effects. Materials and Methods. Rat cervical endplate chondrocytes were cultured and treated with Fas antibody, with or without IGF-1. Cellular morphology was examined by microscopy. Apoptotic changes were evaluated by transmission electron microscopy, TUNEL staining, and immunostaining. Apoptosis-induced changes in the expression of integrin-ā1 chain and FAK were also investigated. Results. Endplate chondrocytes were able to be cultured; a chondrocytic phenotype was maintained. Fas antibody induced apoptosis in endplate chondrocytes; this was confirmed by TUNEL staining. Bcl-2 expression was decreased by Fas antibody, while Bax expression increased. Integrin-ā1 and FAK expression was decreased by Fas antibody. IGF-1 treatment inhibited these Fas antibody-induced changes. Conclusions. Fas antibody induces apoptosis and decreases Integrin-ā1 and FAK expression in cultured endplate chondrocytes; IGF-1 is protective against these changes. ©2006, Lippincott Williams & Wilkins, Inc.link_to_subscribed_fulltex

Cervical intervertebral disc degeneration induced by unbalanced dynamic and static forces: A novel in vivo rat model

STUDY DESIGN. Establishment of a novel in vivo animal model of cervical spondylosis. OBJECTIVE. To investigate apoptotic, degenerative, and inflammatory changes occurring in the cervical intervertebral discs of rats. SUMMARY OF BACKGROUND DATA. Cervical degeneration occurs as the result of imbalance of both static and dynamic spinal stabilizers. The disc degeneration that occurs is characterized by increased local inflammation and increased apoptosis of intervertebral disc cells. METHODS. By excising the paraspinal musculature and posterior cervical spinal ligaments of rats, both static and dynamic cervical stabilizers were disrupted. The resultant biomechanical imbalance resulted in biochemical and histologic changes, which were characterized by light microscopy, electron microscopy, immunostaining, enzyme-linked immunosorbent assay, polymerase chain reaction, and in situ hybridization. RESULTS. Histologic analysis showed characteristic degenerative changes of the intervertebral discs and vertebral endplates following surgery. Ultrastructural examination revealed apoptotic changes, which were verified by immunostaining. Instability also resulted in significant up-regulation of inflammatory factors, as shown by enzyme-linked immunosorbent assay, polymerase chain reaction, and in situ hybridization. CONCLUSIONS. By creating static and dynamic posterior instability of the cervical spine, this novel model of cervical spondylosis results in rapid intervertebral disc degeneration characterized by increased apoptosis and local inflammation, such as that seen clinically. ©2006, Lippincott Williams & Wilkins, Inc.link_to_subscribed_fulltex

Interpretation of Post-operative Distal Humerus Radiographs After Internal Fixation: Prediction of Later Loss of Fixation

Purpose Stable fixation of distal humerus fracture fragments is necessary for adequate healing and maintenance of reduction. The purpose of this study was to measure the reliability and accuracy of interpretation of postoperative radiographs to predict which implants will loosen or break after operative treatment of bicolumnar distal humerus fractures. We also addressed agreement among surgeons regarding which fracture fixation will loosen or break and the influence of years in independent practice, location of practice, and so forth. Methods A total of 232 orthopedic residents and surgeons from around the world evaluated 24 anteroposterior and lateral radiographs of distal humerus fractures on a Web-based platform to predict which implants would loosen or break. Agreement among observers was measured using the multi-rater kappa measure. Results The sensitivity of prediction of failure of fixation of distal humerus fracture on radiographs was 63%, specificity was 53%, positive predictive value was 36%, the negative predictive value was 78%, and accuracy was 56%. There was fair interobserver agreement (κ = 0.27) regarding predictions of failure of fixation of distal humerus fracture on radiographs. Interobserver variability did not change when assessed for the various subgroups. Conclusions When experienced and skilled surgeons perform fixation of type C distal humerus fracture, the immediate postoperative radiograph is not predictive of fixation failure. Reoperation based on the probability of failure might not be advisable. Type of study/level of evidence Diagnostic III