No abstract

No abstract

No abstract

This is the first large long-term comprehensive study of distal radius fractures in older people. The results indicate that factors predictive of distal radius fractures can easily be assessed in routine clinical practice and can identify women at high risk for fracture. Selected preventive strategies could be designed to reduce the incidence of these fractures.

This article describes the clinical application of gene therapy to a nonlethal disease, rheumatoid arthritis (RA). Intraarticular transfer of IL-1 receptor antagonist (IL-1Ra) cDNA reduces disease in animal models of RA. Whether this procedure is safe and feasible in humans was addressed in a phase I clinical study involving nine postmenopausal women with advanced RA who required unilateral sialastic implant arthroplasty of the 2nd-5th metacarpophalangeal (MCP) joints. Cultures of autologous synovial fibroblasts were established and divided into two. One was transduced with a retrovirus carrying IL-1Ra cDNA; the other provided untransduced, control cells. In a dose escalation, double-blinded fashion, two MCP joints were injected with transduced cells, and two MCP joints received control cells. One week later, injected joints were resected and examined for evidence of successful gene transfer and expression by using RT-PCR, ex vivo production of IL-1Ra, in situ hybridization, and immunohistochemistry. All subjects tolerated the protocol well, without adverse events. Unlike control joints, those receiving transduced cells gave positive RT-PCR signals. Synovia that were recovered from the MCP joints of intermediate and high dose subjects produced elevated amounts of IL-1Ra (P ‫؍‬ 0.01). Clusters of cells expressing high levels of IL-1Ra were present on synovia of transduced joints. No adverse events occurred. Thus, it is possible to transfer a potentially therapeutic gene safely to human rheumatoid joints and to obtain intraarticular, transgene expression. This conclusion justifies additional efficacy studies and encourages further development of genetic approaches to the treatment of arthritis and related disorders.clinical trial ͉ interleukin-1 receptor antagonist ͉ retrovirus ͉ synovium