Journal of orthopaedic research : official publication of the Orthopaedic Research Society
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Chemotherapeutic agents have been used for the treatment of patients with osteosarcoma (OS). However, inherent or acquired resistance to these agents is a serious problem in the management of OS patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to induce apoptosis in a variety of cancer cells but not normal cells. ⋯ Consequently, the activated caspase-8 might lead to either activation of effector caspases such as caspase-3 or loss in DeltaPsi(m). Both the increased caspase activation and mitochondrial dysfunction induced by combination of CDDP and TRAIL would contribute to enhanced apoptotic cell death. The results of the present study would be valuable for the design of novel treatment modalities for patients with OS.
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Interfragmentary movements affect the quality and quantity of callus formation. The mounting plane of monolateral external fixators may give direction to those movements. Therefore, the aim of this study was to determine the influence of the fixator mounting plane on the process of fracture healing. ⋯ The group with the anteromedially mounted fixator, initially showing significantly more interfragmentary movements, ended up with a significantly smaller callus diameter and a significantly higher callus stiffness as a result of advanced fracture healing. This demonstrates that the initial phase of healing is sensitive to mechanical conditions and influences the course of healing. Therefore, initial mechanical stability of an osteosynthesis should be considered an important factor in clinical fracture treatment.
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Non-steroidal anti-inflammatory drugs (NSAIDs) specifically inhibit cyclooxygenase (COX) activity and are widely used as anti-arthritics, post-surgical analgesics, and for the relief of acute musculoskeletal pain. Recent studies suggest that non-specific NSAIDs, which inhibit both COX-1 and COX-2 isoforms, delay bone healing. The objectives of this study were 2-fold; first, to measure the relative changes in the normal expression of COX-1 and COX-2 mRNAs over a 42 day period of fracture healing and second, to compare the effects of a commonly used non-specific NSAID, ketorolac, with a COX-2 specific NSAID, Parecoxib (a pro-drug of valdecoxib), on this process. ⋯ Histological analysis at 21 days showed that the calluses in the ketorolac-treated group contained substantial amounts of residual cartilage while neither the control nor the parecoxib-treated animals showed comparable amounts of cartilage at this stage. These results demonstrate that ketorolac and parecoxib delay fracture healing in this model, but in this study daily administration of ketorolac, a non-selective COX inhibitor had a greater affect on this process. They further demonstrate that a COX-2 selective NSAID, such as parecoxib (valdecoxib), has only a small effect on delaying fracture healing even at doses that are known to fully inhibit prostaglandin production.
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This study addressed the question of whether the level of compressive load would affect the conclusions from statistical analyses aimed at determining how well a lateral meniscal autograft restores tibial contact (as indicated by the maximum contact pressure, mean pressure, and contact area) to that of the intact knee. If statistical analyses indicated that normal tibial contact was not restored with a higher, more physiologic load, then a secondary question was whether an autograft surgically implanted with bone plugs would improve tibial contact compared to that in a meniscectomized knee. Nine, fresh-frozen human cadaveric knees were subjected to a low, non-physiologic compressive load of 400 N and a higher, more physiologic compressive load of 1200 N under three conditions (lateral meniscus intact, lateral meniscus removed and reimplanted as an autograft, and lateral meniscus removed). ⋯ Therefore studies designed to evaluate tibial contact pressure for a meniscal transplant should use a higher, more physiologic compressive load, because lower loads overestimate the transplant's effectiveness. Although none of the contact variables was restored to normal when the compressive load was increased to 1200 N, all of the contact variables were more normal than those of the meniscectomized knee. Thus, lateral meniscal allografts implanted using bone plugs can significantly improve contact pressure relative to a meniscectomized knee at the time of implantation.
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Comparative Study
Development of an atrophic nonunion model and comparison to a closed healing fracture in rat femur.
Although most fractures heal, some fail to heal and become nonunions. Many animal models have been developed to study problems of fracture healing. The majority of nonunion models have involved segmental bone defects, but this may not adequately represent the biologic condition in which nonunions clinically develop. ⋯ The radiographical appearance of nonunion models was atrophic. This investigation showed pronounced differences between the experimental nonunions and standard closed fractures both histologically and biomechanically. In conclusion, we have developed a reproducible atrophic nonunion model in the rat femur that simulates the clinical condition in which there is periosteal disruption but no bone defect.