Molecular lysis of synovial lining cells by in vivo herpes simplex virus-thymidine kinase gene transfer.

Herpes simples virus thymidine kinase (HSV-TK) expression plasmid DNA was injected into the joint space of rabbits with antigen-induced arthritis (AIA). Purified plasmid DNA was able to mediate transfection of synovial lining cells and transient overexpression of HSV-TK in the context of active synovial inflammation. The pharmacodynamic distribution of intraarticular expression plasmid DNA was confined to the joint space. Arthritic rabbits treated with intraarticular expression plasmid DNA followed by intravenous ganciclovir (GCV, 5 mg/kg) twice daily for 3 days showed histologic evidence of synovial lining layer cytolysis when articular tissues were examined 21 days posttreatment. There was also a reduction in joint swelling in the TK-treated knees. No untoward clinical effects were observed in the rabbits and no evidence of cytolytic damage specific to the TK-GCV gene therapy was observed either in the articular cartilage or bone. The application of TK-GCV intraarticular gene therapy using purified expression plasmid DNA for the induction of synovial cytolysis may be applicable to the treatment of human inflammatory arthritis.

Early intervention: why, for whom, how, and at what cost?

When the concept of intervention is applied to human development, the goal is usually to enhance functioning or to prevent some unwanted condition. During the past 20 years, the United States has committed itself to an early intervention position for young children who are socio-economically, educationally, or physically disadvantaged. This article summarizes the knowledge base concerning early educational interventions and to recommend actions concerning public policy and associated research.