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STUDY DESIGN: Prospective study. OBJECTIVE: To identify proteins with differential expression in the cerebrospinal fluid (CSF) from 15 clinically normal (control) dogs and 15 dogs with cervical spondylomyelopathy (CSM). SUMMARY OF BACKGROUND DATA: Canine CSM is a spontaneous, chronic, compressive cervical myelopathy similar to human cervical spondylotic myelopathy. There is a limited knowledge of the molecular mechanisms underlying these conditions. Differentially expressed CSF proteins may contribute with novel information about the disease pathogenesis in both dogs and humans. METHODS: Protein separation was performed with 2-dimensional electrophoresis. A Student t test was used to detect significant differences between groups (P < 0.05). Three comparisons were made: (1) control versus CSM-affected dogs, (2) control versus non-corticosteroid-treated CSM-affected dogs, and (3) non-corticosteroid-treated CSM-affected versus corticosteroid-treated CSM-affected dogs. Protein spots exhibiting at least a statistically significant 1.25-fold change between groups were selected for subsequent identification with capillary-liquid chromatography tandem mass spectrometry. RESULTS: A total of 96 spots had a significant average change of at least 1.25-fold in 1 of the 3 comparisons. Compared with the CSF of control dogs, CSM-affected dogs demonstrated increased CSF expression of 8 proteins including vitamin D-binding protein, gelsolin, creatine kinase B-type, angiotensinogen, α-2-HS-glycoprotein, SPARC (secreted protein, acidic, rich in cysteine), calsyntenin-1, and complement C3, and decreased expression of pigment epithelium-derived factor, prostaglandin-H2 D-isomerase, apolipoprotein E, and clusterin. In the CSF of CSM-affected dogs, corticosteroid treatment increased the expression of haptoglobin, transthyretin isoform 2, cystatin C-like, apolipoprotein E, and clusterin, and decreased the expression of angiotensinogen, α-2-HS-glycoprotein, and gelsolin. CONCLUSION: Many of the differentially expressed proteins are associated with damaged neural tissue, bone turnover, and/or compromised blood-spinal cord barrier. The knowledge of the protein changes that occur in CSM and upon corticosteroid treatment of CSM-affected patients will aid in further understanding the pathomechanisms underlying this disease. LEVEL OF EVIDENCE: N/A.

Approximately 2 million patients in the United States annually undergo total joint arthroplasty with reaming and placement of intramedullary nails, resulting in extravasation of bone marrow and fat into the circulatory system and potentially causing fat embolism syndrome. Acute and chronic changes in mental status documented after these procedures may be related to embolic events. The Reamer/Irrigator/Aspirator (RIA) device has been shown to decrease intramedullary pressure during reaming. We hypothesized that the use of the RIA in a canine model would reduce the number of microemboli detected in the carotid artery and brain compared with nailing either with or without reaming.Twenty-four large canines underwent unreamed nailing (UR), sequentially reamed nailing (SR), or RIA-reamed nailing (RIA) of bilateral femora (eight dogs per group). During reaming and nailing, the number and size of microemboli transiting the carotid artery were recorded. After euthanasia, the brain was harvested for immunostaining and measurement of microinfarction volumes.Total embolic load passing through the carotid artery was 0.049 cc (UR), 0.045 cc (SR), and 0.013 cc (RIA). The number and size of microemboli in the UR and SR groups were similar; however, the RIA group had significantly fewer larger-sized (200-μm) emboli (p = 0.03). Pathologic examination of the brain confirmed particulate emboli, and histologic analyses demonstrated upregulation of stress-related proteins in all groups, with fewer emboli and less evidence of stress for RIA reaming.RIA reaming decreased microemboli compared with traditional reaming and unreamed nailing, suggesting that intramedullary pressure and heat are important variables. The documented embolic events and brain stress may help to explain subtle neurobehavioral symptoms commonly seen in patients after undergoing long-bone reaming procedures.RIA reaming decreased cranial embolic events and may have an ameliorating effect on postoperative neurologic sequelae.

Background: Unloading treatments for osteoarthritis of the knee, such as valgus braces, have been shown to reduce medial joint-loading and pain. The purpose of this preclinical study was to investigate the tissue response to an extracapsular implantable device (KineSpring System; Moximed, Hayward, California) that is designed to reduce loading across the medial compartment of the knee. Methods: Eleven sheep were implanted with the KineSpring System, consisting of bases secured to the medial femoral and tibial cortices with bone screws and also consisting of a joint-spanning load-absorber composed of a piston and spring assembly inside a polymeric sheath. In nine sheep, titanium alloy washers with either an uncoated or a plasma-sprayed titanium-hydroxyapatite (TPS-HA) coated undersurface were fixed with screws to the contralateral femur and tibia to investigate the effects of surface treatment on extracortical bone apposition. The functionality of the KineSpring System was assessed by fluoroscopy, tissue response was determined by gross and microscopic histology, and implant fixation was determined by radiography, microradiography, and histomorphometry at four, twelve, twenty-six, and fifty-two weeks. Results: The function of the KineSpring System was confirmed in all sheep. Seventeen of eighteen TPS-HA coated bases and thirty-six of thirty-six washers had stable bone fixation; one coated base was loose with evidence of infection. At four weeks, there was an early, expected inflammatory response, but this response resolved by twelve weeks and a pseudosynovial membrane formed around the sheath. Bone apposition increased over time for the TPS-HA coated bases and for uncoated washers (p < 0.05). There was good apposition of the TPS-HA coated washers even at early time points, with no subsequent increase in apposition over time. Conclusions: The KineSpring System demonstrated safety in a simulated use model for periods of up to fifty-two weeks. Screws result in stable implant fixation and TPS-HA coating allows for early and long-lasting cortical bone apposition and integration. Clinical Relevance: This implant warrants further investigation as a means of reducing medial compartment loading and pain in patients with osteoarthritis of the knee.

At therapeutic levels in pediatric patients, radiation causes damage to the growth plate and contributes to growth deformity and fractures. The purpose of this project was to examine the effects of x-ray irradiation on regional bone mineral density (BMD) and osteoclast histology of rat bone with and without radioprotectant amifostine (AMF) pretreatment. Seventy-two weanling rats had their right knee irradiated with single fraction 17.5 Gy, whereas the left leg was used as an internal control. Twelve animals were euthanized at each of 6 time periods (0.5-6 wk) after irradiation, half having received 100 mg/kg amifostine. BMD (g/cm3) was determined for both the right and left femurs using peripheral quantitative computed tomography (CT) (pQCT). Tibial sections were stained for osteoclasts/chondroclasts with tartrate-resistant acid phosphatase. Statistically significant increases in BMD within the radiation field were seen in the treatment groups' right irradiated legs over the control unirradiated left legs at all time points from 0.5 through 6 weeks. Anatomically, a peak in BMD occurs in the region immediately adjacent to the chondro-osseous junction at 2 weeks after irradiation and then moves proximally within the adjacent metaphysis after 3 weeks. Corresponding to these findings, histologically a 2-week nadir occurs after irradiation in osteoclasts/chondroclast numbers adjacent to the chondro-osseous junction with a 71.9% decrease compared with controls (p

Aseptic loosening is the most common indication for revision surgery in total hip arthroplasty (THA) and total knee arthroplasty (TKA). Radiostereometric analysis (RSA), considered the benchmark for in vivo evaluation of implant fixation, provides a sensitive method for detecting implant migration. Available evidence from patients who have undergone TKA suggests that excessive early migration (>0.2 mm within the second postoperative year) is a strong indicator of components that will eventually become clinically loose. RSA migration data reflect permanent motions that have occurred between the implant and the surrounding bone; these data do not provide detailed information about real-time micromotion that may be occurring at the interface of a loaded implant. In an effort to provide qualitative and quantitative data regarding the stability of total joint arthroplasty implants, attention has focused on the development of sensitive techniques for assessing dynamic micromotion around cemented and noncemented total joint arthroplasties. In vivo measurements of inducible micromotion have been reported using RSA, but this technique is an order of magnitude less sensitive than direct mechanical testing of the implants in vitro. Destructive and nondestructive mechanical tests have been widely used to quantify the strength of the implant-bone interface, but less attention has been paid to measuring micromotion in response to loading and, in particular, to the determination of relative motions between the implant, cement mantle, and periprosthetic bone in cemented total joint arthroplasties. Several recent studies have highlighted a novel methodology for examining local interface motions around total joint arthroplasty implants. Central to these experiments has been the use of digital image correlation (DIC), a technique in which relative motions between different regions of an interface are quantified by measuring changes in the relative position of microscopic landmarks under mechanical loading. Although previously used to determine changes in strain pattern adjacent to loaded implants, DIC has now been used to perform high-resolution mapping of micromotion across the interfaces of retrieved cemented and noncemented total hip and knee replacement implants. The retrieved implants are sectioned into slabs approximately 5 to 10 mm thick using high-speed sectioning techniques that effectively preserve the integrity of the implant-bone, cement-bone, and implant-cement interfaces. A fine mist of black paint is applied to the interface tissues to provide surface texture for the imaging process; micromotion across the interface zones is quantified by measuring relative motion between individual topographic features that have picked up the paint. Using DIC, motions on the order of microns may be detected; just as importantly, the location of the motions can be determined. In a series of cemented THA retrievals subjected to gait loading conditions, this “functional micromechanics” approach was used to Matthew J. Allen, Vet MB, PhD

Gelatin sponge (Gelfoam; Upjohn, Kalamazoo, MI, U.S.A.) is commonly used as an interpositional barrier to shield the spinal cord from thermal injury during vertebral reconstruction with polymethylmethacrylate bone cement. The aim of this study was to record epidural and intradural temperatures during polymethylmethacrylate reconstruction of vertebral corpectomy defects. Three surgical techniques (subtotal corpectomy, total corpectomy with insertion of a Gelfoam barrier, and total corpectomy with no barrier) were compared in vivo and in vitro in a porcine model. As expected, total corpectomy defects cemented without a Gelfoam barrier produced the highest epidural temperatures in vivo (52.8 degrees C) and in vitro (58 +/- 2 degrees C). The Gelfoam barrier provided some protection against heat transfer, but peak temperatures and absolute temperature increases were significantly higher than in defects with an intact posterior cortex (p < 0.05). These results indicate that an intact posterior cortex provides the best protection against heat transfer, whereas the use of a Gelfoam barrier appears to provide only partial protection against thermal injury.