Relational coordination across health care providers is associated with improved quality of care, reduced postoperative pain, and decreased lengths of hospital stay for patients undergoing total joint arthroplasty. These findings support the design of formal practices to strengthen communication and relationships among key caregivers on surgical units.
Objective. To evaluate the effect of a short preoperative exercise intervention on the functional status, pain, and muscle strength of patients before and after total joint arthroplasty. Methods. A total of 108 men and women scheduled for total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomized to a 6-week exercise or education (control) intervention immediately prior to surgery. We assessed outcomes through questionnaires and performance measures. Analyses examined differences between groups over the preoperative and immediate postoperative periods and at 8 and 26 weeks postsurgery. Results. Among THA patients, the exercise intervention was associated with improvements in preoperative Western Ontario and McMaster Universities Osteoarthritis Index function score (improvement of 2.2 in exercisers versus decline of 3.9 in controls; P ؍ 0.02) and Short Form 36 physical function score (decline of 0.4 in exercisers versus decline of 14.3 in controls; P ؍ 0.003). No significant differences were seen in TKA patients. Exercise participation increased muscle strength preoperatively (18% in THA patients and 20% in TKA patients), whereas the control patients had essentially no change in strength (P > 0.05 for exercise versus education in both THA and TKA groups). Exercise participation prior to total joint arthroplasty substantially reduced the risk of discharge to a rehabilitation facility in THA and TKA patients (adjusted odds ratio 0.27, 95% confidence interval 0.074 -0.998). The intervention had no effects on outcomes 8 and 26 weeks postoperatively. Conclusion. A 6-week presurgical exercise program can safely improve preoperative functional status and muscle strength levels in persons undergoing THA. Additionally, exercise participation prior to total joint arthroplasty dramatically reduces the odds of inpatient rehabilitation.
Currently, an in vivo model of human breast cancer metastasizing from the orthotopic site to bone does not exist, making it difficult to study the many steps of skeletal metastasis. Moreover, models used to identify the mechanisms by which breast cancer metastasizes to bone are limited to intracardiac injection, which seeds the cancer cells directly into the circulation, thus bypassing the early steps in the metastatic process. Such models do not reflect the full process of metastasis occurring in patients. We have developed an animal model of breast cancer metastasis in which the breast cancer cells and the bone target of osteotropic metastasis are both of human origin. The engrafted human bone is functional, based on finding human IgG in the mouse bloodstream, human B cells in the mouse spleen, and normal bone histology. Furthermore, orthotopic injection of a specific human breast cancer cell line, SUM1315 (derived from a metastatic nodule in a patient), later resulted in both bone and lung metastases. In the case of bone, metastasis was to the human implant and not the mouse skeleton, indicating a species-specific osteotropism. This model replicates the events observed in patients with breast cancer skeletal metastases and serves as a useful and relevant model for studying the disease. (Cancer Res 2005; 65(14): 6130-38)
Objective
Our previous study suggested that growth arrest and DNA damage–inducible protein 45β (GADD45β) prolonged the survival of hypertrophic chondrocytes in the developing mouse embryo. This study was undertaken, therefore, to investigate whether GADD45β plays a role in adult articular cartilage.
Methods
Gene expression profiles of cartilage from patients with late-stage osteoarthritis (OA) were compared with those from patients with early OA and normal controls in 2 separate microarray analyses. Histologic features of cartilage were graded using the Mankin scale, and GADD45β was localized by immunohistochemistry. Human chondrocytes were transduced with small interfering RNA (siRNA)–GADD45β or GADD45β-FLAG. GADD45β and COL2A1 messenger RNA (mRNA) levels were analyzed by real-time reverse transcriptase–polymerase chain reaction, and promoter activities were analyzed by transient transfection. Cell death was detected by Hoechst 33342 staining of condensed chromatin.
Results
GADD45β was expressed at higher levels in cartilage from normal donors and patients with early OA than in cartilage from patients with late-stage OA. All chondrocyte nuclei in normal cartilage immunostained for GADD45β. In early OA cartilage, GADD45β was distributed variably in chondrocyte clusters, in middle and deep zone cells, and in osteophytes. In contrast, COL2A1, other collagen genes, and factors associated with skeletal development were up-regulated in late OA, compared with early OA or normal cartilage. In overexpression and knockdown experiments, GADD45β down-regulated COL2A1 mRNA and promoter activity. NF-κB overexpression increased GADD45β promoter activity, and siRNA-GADD45β decreased cell survival per se and enhanced tumor necrosis factor α–induced cell death in human articular chondrocytes.
Conclusion
These observations suggest that GADD45β might play an important role in regulating chondrocyte homeostasis by modulating collagen gene expression and promoting cell survival in normal adult cartilage and in early OA.
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