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Objective: To (1) investigate the tissue response to a novel urethral bulking agent, polyethylene glycol carboxymethyl cellulose hydrogel (PEG-CMC) injected submucosally in the canine urethra and (2) compare PEG-CMC with bovine collagen (BC), the current standard for urethral bulking., Study Design: Experimental study., Animals: Purpose-bred female hound dogs (n = 8)., Methods: Standardized submucosal urethral injections of BC and PEG-CMC were performed in 8 female dogs. Injection sites were evaluated by cystoscopy on days 0 (n = 8), 30 (n = 4), and 90 (n = 4), magnetic resonance imaging on days 0 (n = 8), 30 (n = 8), and 90 (n = 4) and by histopathology on days 30 (n = 4) and 90 (n = 4)., Results: Both PEG-CMC and BC were detectable on MRI as hyperintense foci on T2-weighted images. Grossly, PEG-CMC formed more prominent blebs than BC. On follow-up cystoscopic examination, 6/8 PEG-CMC injection needle tracts were visible, and 3 of these sites had mucosal erosions. Histopathologic scores for foreign body reaction and inflammation were significantly higher for PEG-CMC compared with BC (P < 0.005). BC elicited a lymphoplasmacytic reaction whereas PEG-CMC incited a granulomatous response., Conclusions: The overall physical characteristics and histologic response associated with PEG-CMC support its use as a urethral bulking agent; however, the current formulation needs to be adjusted for clinical use., (© Copyright 2012 by The American College of Veterinary Surgeons.)

Objective: To compare the efficacy of 2 doses of recombinant human bone morphogenetic protein-2 (rhBMP-2) on tibial osteotomy healing in dogs., Study Design: Experimental, randomized complete block (n=7)., Animals: Adult female dogs (n=21)., Methods: Right midshaft tibial osteotomies were created and stabilized with a 1-mm gap using type I external fixators. Seven dogs were untreated controls and 14 with osteotomies were treated with either 0.05 or 0.2 mg/mL rhBMP-2 delivered in an absorbable collagen sponge (ACS). At 8 weeks, dogs were euthanatized and bones were mechanically tested and examined by microscopy., Results: Bone healing based on radiographic scoring, was significantly improved in dogs treated with 0.2 mg/mL of rhBMP-2 compared with the other groups; these tibiae were also significantly stronger and stiffer than 0.05 mg/mL rhBMP-2 and control osteotomized tibiae. Histologic scores were significantly better for 0.2 mg/mL rhBMP-2 group than 0.05 mg/mL rhBMP-2 group, but neither was significantly different from control., Conclusions: rhBMP-2 in ACS at a concentration of 0.2 mg/mL improves healing of tibial osteotomies in dogs compared with untreated controls and 0.05 mg/mL rhBMP-2 based on force plate analysis and radiographic evaluation. This was not confirmed histologically but treated bones had improved mechanical properties at 8 weeks., Clinical Relevance: After a long bone fracture, dogs may face a long recovery period before full return of limb function. rhBMP-2, in association with good fracture fixation principles, may enhance bone healing in dogs with diaphyseal fractures.

Objectives: To evaluate the effects of intra-articular protection (IAP) on the canine cranial cruciate ligament (CrCL) and stifle in a CrCL midsubstance elongation injury model., Study Design: Experimental longitudinal cohort study., Animals: Skeletally mature female mixed breed hounds (n=12; mean+/-SEM weight, 25.6+/-0.7 kg)., Methods: After CrCL elongation in 1 stifle of each dog, IAP was applied in 6 joints. In vivo assessment included radiographs, cranial-caudal joint translation, gait analysis, and synovial fluid levels of 3B3(-) (proteoglycan epitope) and C2C (collagen II neoepitope) up to 12 weeks after surgery. Joint translation and rotation were quantified at necropsy. CrCL midsubstance length was determined before and after elongation and at necropsy. CrCLs were subjectively assessed with light microscopy. Comparisons were made between stifles containing elongated CrCLs with and without IAP and unoperated controls., Results: Four weeks after surgery, ground reaction forces were significantly decreased in operated limbs. Absolute C2C levels were significantly elevated in operated stifles 4 weeks post-surgery. C2C and 3B3(-) levels normalized to total protein were significantly elevated in IAP+ stifles 8 weeks after surgery. Protected CrCLs appeared to have decreased granulation tissue and better collagen fiber alignment., Conclusions: IAP has negligible effects on the canine stifle based on the response variables evaluated in this 12-week study. Protection of elongated CrCLs may promote reduced, organized scar formation., Clinical Relevance: These results support the healing capacity of the canine CrCL midsubstance following elongation injury and IAP application to potentially reduce cicatrix formation in elongated CrCLs.

Objective: Evaluation of the relationship between canine weight gain from 6 to 15 weeks of age and passive coxofemoral joint (CFJ) laxity at 16 weeks of age., Study Design: Longitudinal cohort study., Animals: Full- or half-sibling hounds (n = 56)., Methods: Hounds were weighed weekly from 6 to 15 weeks of age. Individual average daily gain (ADG) was calculated for each week (weekly) and for the study (overall). PennHIP distraction index (DI) was determined for each CFJ at 16 weeks. Mixed effects linear models were evaluated for associations of DI (highest and mean) with 15-week weight and ADGs (actual or normalized). Left and right DIs were compared with a Student's paired t-test. Significance was set at P<.05. Trends were considered at P<.10., Results: Mean (+/-SD) 16-week DI score and 15-week weight was 0.67 +/- 0.16 and 12.5 +/- 1.8 kg, respectively. Within animal left and right DIs were not significantly different. There were no significant associations between DI and any of the weight gains evaluated. There was a trend for a negative relationship between normalized 14-week ADG and DI in one statistical model., Conclusions: Weight gain from 6 to 15 weeks of age was unrelated to 16-week PennHIP DI in a homogenous canine population with moderate-to-severe CFJ joint laxity., Clinical Relevance: Based on our results, ad libitum feeding between 6 and 15 weeks of age does not appear to have an adverse impact on joint laxity at 16 weeks of age as measured by the PennHIP DI.

Objective: To determine fibroblast viability, assess development of apoptosis, and evaluate tissue hypoxia via histochemical, in-situ hybridization, or immunohistochemical staining in ruptured and intact cranial cruciate ligaments (CCLs) of dogs., Animals: 32 dogs with ruptured CCLs, and 8 aged and 19 young dogs with intact CCLs., Procedure: Markers of cell viability (lactate dehydrogenase [LDH]), apoptosis (terminal deoxynucleatidyl transferase-mediated deoxyuridine triphosphate-nick end labeling [TUNEL] method), and hypoxia (hypoxia-inducible factor-1alpha [HIF-1alpha] monoclonal antibody) were applied to CCL specimens; positive cells were assessed objectively (LDH) and subjectively (TUNEL and HIF-1alpha) in the main axial tissue component (core) and synovial intima and subintima (epiligamentous tissue)., Results: Viable fibroblasts were seen in all intact and ruptured CCLs. More nonviable cells were found in the core regions of ruptured CCLs and intact CCLs of young dogs than in the epiligamentous regions. Number of nonviable cells in the core region of ruptured CCLs was greater than that in intact CCLs of young and aged dogs, whereas the number in the epiligamentous region was similar in all specimens. The TUNEL and HIF-1alpha staining was only found in the epiligamentous region of ruptured CCLs., Conclusions and Clinical Relevance: Ruptured CCLs contained a high number of nonviable cells but not a great number of apoptotic cells. Repair processes in the epiligamentous region of the CCL include a metabolic response to hypoxia, suggesting that necrosis of ligament fibroblasts and transformation of surviving cells to a spheroid phenotype may be a response to hypoxia cause by microinjury or inadequate blood flow.

Objective: To investigate the harvest and application of hamstring grafts for canine cranial cruciate ligament (CrCL) reconstruction., Study Design: Experimental study., Animals: Four adult female hounds, weighing 26.3 +/- 1.6 kg (mean +/- SEM). METHODS-One stifle in each dog was randomly chosen for hamstring graft CrCL reconstruction after native CrCL transection. Arthroscopy was performed to evaluate graft integrity at 12 weeks. Gait analysis and stifle radiographs were performed preoperatively and up to 52 weeks after graft placement. Dogs were killed 12 (n = 2) or 52 weeks (n = 2) after CrCL reconstruction. Tissues were evaluated grossly and with light and confocal laser microscopy., Results: Hamstring grafts were intact in all stifles at 12 weeks (n = 4) and 52 weeks (n = 2). Grossly, there was no osteoarthritis in stifles at 12 weeks and only chondrophytes along the trochlear ridges at 52 weeks. Minimal radiographic evidence of osteoarthritis developed in stifles with grafts during the study. Lameness in limbs with grafts resolved by 52 weeks. Graft tissue was highly vascular, ligamentized, and undergoing active remodeling at 12 weeks. Fifty-two weeks after graft placement, intraarticular graft tissue was well vascularized, mature, and encapsulated by synovium, and graft-bone interfaces were characterized by Sharpey's fiber insertions. There was no evidence of graft necrosis using confocal laser microscopy at either time point., Conclusions: The hamstring graft technique may be a viable method of canine CrCL reconstruction., Clinical Relevance: Hamstring grafts may be an alternative technique for canine CrCL reconstruction. Further study is needed before clinical application., (Copyright 2003 by The American College of Veterinary Surgeons)

Objectives: To determine changes to the cells and collagenous and amorphous extracellular matrix (ECM) structure in ruptured canine cranial cruciate ligaments (CCL)., Study Design: Prospective clinical study., Animals: CCL specimens obtained from 29 dogs with ruptured CCL and 6 young dogs with intact CCL., Methods: Ligament fibroblast number density and phenotype were determined in the core and epiligamentous regions. ECM birefringence and crimp structure in the core region were also studied., Results: Loss of fibroblasts from the core region of ruptured CCL was seen (P <.001), whereas, in the epiligamentous region, cell number densities were similar in ruptured and intact CCL (P =.7). In ruptured CCL, numbers of typical ligament fibroblasts (fusiform and ovoid cells) were decreased, and numbers of cells exhibiting chondroid transformation (spheroid cells) were increased in the core region (P <.001). Expansion of the volume of the epiligamentous region was also seen, although bridging scar tissue was not seen between the ends of ruptured CCL. The structure of the ECM collagen in the core region was extensively disrupted in ruptured CCL. This was, in part, because of decreased birefringence and elongation of the crimp in the remaining collagen fibers when compared with intact CCL (P <.01)., Conclusions: Extensive alterations to the cell populations and collagenous ECM structure were seen in ruptured CCL. Although a proliferative epiligamentous repair response was seen in ruptured CCL, there was a lack of any bridging scar between the ruptured ends of the CCL., Clinical Relevance: The cellular and ECM changes in ruptured CCL that we have described appear to result from the cumulative effects of remodeling and adaptation to mechanical loading and microinjury. Treatment of early cruciate disease in dogs will need to inhibit or reverse these progressive changes to CCL tissue, which are directly associated with partial or complete structural failure of the CCL under conditions of normal activity., (Copyright 2003 by The American College of Veterinary Surgeons)

This study was to determine the efficacy of recombinant human bone morphogenetic protien-2 (rhBMP-2)/calcium phosphate matrix (CPX) paste to accelerate healing in a canine articular fracture model with associated subchondral defect. rhBMP-2/CPX (BMP), CPX alone (CPX) or autogenous bone graft (ABG) was administered to a canine articular tibial plateau osteotomy with a subchondral defect in each of 21 female dogs. The unoperated contralateral limbs served as controls. Ground reaction forces, synovial fluid, radiographic changes, mechanical testing, bone density, and histology of bone and synovium were analyzed at 6 weeks after surgery. Radiographic analysis demonstrated that the BMP and CPX groups showed improved bony healing compared to the ABG group at week 6. Histomorphometric analysis demonstrated that the BMP group had significantly increased trabecular bone volume compared to the CPX and ABG groups. Mechanical testing revealed that the BMP group had significantly greater maximum failure loads than the ABG group. Histological analysis demonstrated that the BMP group had significantly less sub-synovial inflammation than CPX group. This study demonstrated that rhBMP-2/CPX accelerated healing of articular fractures with subchondral defect compared to ABG in most of the parameters evaluated, and had less subsynovial inflammation than the CPX alone in a canine model. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 466-471, 2009 [ABSTRACT FROM AUTHOR]

Objective--To quantify and compare the microscopic changes in articular cartilage (AC), zone of calcified cartilage (ZCC), and subchondral bone plate in femoral heads from clinically normal dogs and dogs with moderate or severe osteoarthritis, Sample Population--Femoral heads from clinically normal dogs (n = 16) and dogs with moderate (24) or severe (14) osteoarthritis Procedures--Femoral heads were allocated to 3 categories (normal, moderate, or severe osteoarthritis) on the basis of radiographic findings, macroscopic findings, and histologic grade determined by use of a modified Mankin scale. Equally spaced 2-mm sections were cut in each femoral head in a coronal or transverse plane Thickness of the AC, ZCC, and subchondral bone plate was recorded. Results--Mean thickness of AC was significantly greater in samples with moderate and severe osteoarthritis than those considered normal. Mean thickness of the ZCC was significantly greater in samples with moderate and severe osteoarthritis than those considered normal. Mean thickness of the subchondral bone plate in samples with severe osteoarthritis was significantly greater than those with moderate osteoarthritis and those considered normal. A significant decrease in AC thickness was detected in the proximomedial area of femoral heads with severe osteoarthritis, compared with those considered normal. Conclusions and Clinical Relevance--A cause and effect association between thickening of subchondral structures and thinning and loss of the overlying AC was not detected. Changes in AC were associated with changes in the subchondral bone plate, which is compatible with the theory of adaptation in response to altered load distribution. [ABSTRACT FROM AUTHOR]

Background: In this study, we evaluated the capacity of a single percutaneous injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a rapidly resorbable calcium phosphate paste (alpha-BSM) to accelerate bone-healing in a canine tibial osteotomy model. We hypothesized that the osteotomy sites would heal faster after percutaneous delivery of rhBMP-2/alpha-BSM than they would after injection of alpha-BSM alone or after no treatment.Methods: Bilateral tibial osteotomy was performed and the sites were stabilized with external fixators in sixteen dogs. Four hours after the surgery, one limb of each dog was treated with a single percutaneous injection of rhBMP-2/alpha-BSM paste or an equal volume of alpha-BSM alone. There were eight limbs in each group, and the osteotomy site in the contralateral limb served as an untreated control. The results were evaluated with serial radiography and force-plate analysis at four and eight weeks after surgery and with mechanical testing and histologic examination at eight weeks after the surgery.Results: At four and eight weeks after the osteotomy and treatment, the scores for radiographic union were significantly greater for the rhBMP-2/alpha-BSM-treated limbs than they were for the alpha-BSM-treated or untreated, control limbs (p < 0.05). The callus area in the rhBMP-2/alpha-BSM-treated limbs was significantly greater than that in the alpha-BSM-treated and untreated, control limbs at four and eight weeks postinjection (p < 0.05). The time-integrated vertical force for the rhBMP-2-treated limbs was significantly greater than that for their contralateral controls at four weeks and significantly greater than that for the treated and control limbs of the alpha-BSM-treated dogs at four and eight weeks after the surgery (p Conclusions: This study demonstrates the capacity of a single percutaneous injection of rhBMP-2 delivered in a resorbable calcium phosphate paste (alpha-BSM) four hours after surgery to accelerate the healing of tibial osteotomy sites in a canine model. [ABSTRACT FROM AUTHOR]

Objective To quantify long-term bone adaptation after stable cemented total hip arthroplasty (cTHA) in dogs. Study Design Clinical study. Animals Fourteen dogs. Methods Femoral specimens were collected from client-owned dogs that were donated after death because of causes unrelated to their cTHA. Mean (±SEM) dog age was 11.4±0.7 years and implant duration was 5.3±0.7 years. Implant stability was established from radiographic signs and gross mechanical stability. Femurs were evaluated at 3 levels based on implant length: proximal stem (PS), mid-stem (MS), and distal to stem (DS). Cortical area, medullary area, and porosity were measured at each level. Implanted femurs were compared to contralateral nonimplanted femurs. Results Cortical area and cortical porosity were significantly increased in implanted femurs compared to nonimplanted femurs. Cortical area was increased at the MS and DS levels, and porosity was increased at the PS and MS levels in implanted femurs. Porosity was greatest in the endosteal region at the PS and MS levels in implanted femurs. Conclusions Significant differences in femoral geometry and cortical porosity were detected after long-term stable cTHA. Net bone loss proximally and increased bone mass distally support stress shielding as a important mechanical factor associated with bone adaptation. Distribution of porosity shifts to endosteal regions after long-term cTHA. Clinical Relevance Significant site-specific femoral adaptation occurs in response to stable cTHA and may precede implant loosening. [ABSTRACT FROM AUTHOR]

Objective To evaluate femoral adaptation after unstable long-term cemented total hip arthroplasty (cTHA) in dogs. Study Design Clinical study. Animals Four dogs. Methods Paired femurs were examined from client-owned dogs that were donated to a retrieval program after death from causes unrelated to their cTHA. Mean (±SEM) dog age was 10.0±1.5 years and implant duration was 6.0±1.4 years. Implanted femurs had radiographic changes associated with implant loosening and gross mechanical instability at femur retrieval. Femurs were evaluated at 3 levels relative to implant length. Cortical area and medullary area were measured at each level, and cortical porosity was assessed at each level in 4 quadrants and in 3 regions. Implanted femurs were compared with the contralateral non-implanted femurs. Results Cortical area and cortical porosity were increased at all levels in femurs with unstable implants. Implanted femurs had increased porosity in all quadrants and regions at the proximal 2 levels, and increased porosity in only the cranial quadrant and mid-cortical area at the distal level, when compared with contralateral non-implanted femurs. Corresponding medullary areas were not different. Conclusions Significant histomorphometric changes occur in femurs after unstable cTHA. The patterns of periosteal bone formation and endosteal bone resorption support mechanisms of stress shielding and wear debris-mediated osteolysis as factors that may contribute to femoral adaptation and implant loosening. Clinical Relevance Despite popularity and excellent return to function with cTHA, aseptic loosening remains a serious long-term complication. Substantial net bone loss and unfavorable environment with unstable cTHA may make revision surgery less successful. [ABSTRACT FROM AUTHOR]