Interleukin-1 (IL-1) is a proinflammatory cytokine that has been implicated in wear-debris associated total joint replacement failure. We hypothesized that the absence of the IL-I type-1 receptor would mitigate the inflammatory response to titanium particles and decrease periprosthetic inflammatory tissue in a murine intramedullary rod model. Methods: An intramedullary rod with and without commercially pure titanium particles was placed in the femora of 24 wild type mice (WT) and 24 mice lacking a functional type-1 receptor to IL-1. Femora were analyzed histologically and by ELTSA.of organ culture explant supernatants. Results: The presence of titanium particles in WT mice stimulated increased expression of interleukin-6 (IL-6) and macrophage chemoattractant protein-1 (MCP-1) relative to rod only controls. In contrast, IL-6 and MCP-1 expression were diminished in IL-lrl-KO mice exposed to titanium particles. Additionally, the formation of a periprosthetic fibro-inflammatory membrane in IL-1 rl -KO mice was blunted at 2 weeks when compared to that in wild-type mice. Inflammatory changes and the quality of periprosthetic bone of IL-lrl-KO mice was similar to WT mice in response to titanium particles. Conclusions: These results implicate IL-I as an important modulator in the local inflammatory response to intramedullary titanium particles. MCP-1 appears to be significantly modulated in IL-lrl-KO mice in response to titanium particles. This may be responsible, in part, for the diminished periprosthetic membrane observed in IL-lrl-KO mice at 2 weeks. Expansion of this murine model of intramedullary particle-induced inflammation to other gene targets may contribute to a more mechanistic understanding of wear-debris associated prosthesis failure.
Conceived as a solution to clinical dilemmas, and now required by organizations for hospital accreditation, ethics committees have been subject only to small-scale studies. The wide use of ethics committees and the diverse roles they have played compel study. In 1999 the University of Pennsylvania Ethics Committee Research Group (ECRG) completed the first national survey of the presence, composition, and activities of U.S. healthcare ethics committees (HECs). Ethics committees are relatively young, on average seven years in operation. Eighty-six percent of ethics committees report that they played a role in ongoing clinical decision making through clinical ethics consultation. All are engaged in developing institutional clinical policy. Although 4.5% of HECs write policy on managed care, 50% of HEC chairs feel inadequately prepared to address managed care. The power and activity of ethics committees parallels the composition of those committees and the relationship of members to their institutions. The role of ethics committees across the nation in making policies about clinical care is greater than was known, and ethics committees will likely continue to play an important role in the debate and resolution of clinical cases and clinical policies.
In 1992, the Joint Commission on the Accreditation of Healthcare Organizations ( JCAHO) passed a mandate that all its approved hospitals put in place a means for addressing ethical concerns. Although the particular process the hospital uses to address such concerns-ethics consultant, ethics forum, ethics committee-may vary, the hospital or healthcare ethics committee (HEC) is used most often. In a companion study to that reported here, we found that in 1998 over 90% of U.S. hospitals had ethics committees, compared to just 1% in 1983, and that many have some and a few have sweeping clinical powers in hospitals.
In this model, a single bolus of UHMWPE particles had a long-term effect on gene transcription in mononuclear cells which perpetuated a chronic inflammatory state. This murine model of intramedullary particle-induced inflammation simulates periprosthetic events associated with implant wear in humans, and may contribute to a more mechanistic understanding of wear-debris associated prosthesis failure.
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