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- Author or Editor: C. Wayne McIlwraith x
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Abstract
Objective—To evaluate the temporal pattern of prostaglandin (PG) E2 concentrations in synovial fluid after transection of the cranial cruciate ligament (CCL) in dogs and to correlate PGE2 concentrations with ground reaction forces and subjective clinical variables for lameness or pain.
Animals—19 purpose-bred adult male Walker Hounds.
Procedure—Force plate measurements, subjective clinical analysis of pain or lameness, and samples of synovial fluid were obtained before (baseline) and at various time points after arthroscopic transection of the right CCL. Concentrations of PGE2 were measured in synovial fluid samples, and the PGE2 concentrations were correlated with ground reaction forces and clinical variables.
Results—The PGE2 concentration increased significantly above the baseline value throughout the entire study, peaking 14 days after transection. Peak vertical force and vertical impulse significantly decreased by day 14 after transection, followed by an increase over time without returning to baseline values. All clinical variables (eg, lameness, degree of weight bearing, joint extension, cumulative pain score, effusion score, and total protein content of synovial fluid, except for WBC count in synovial fluid) increased significantly above baseline values. Significant negative correlations were detected between PGE2 concentrations and peak vertical force (r, –0.5720) and vertical impulse (r, –0.4618), and significant positive correlations were detected between PGE2 concentrations and the subjective lameness score (r, 0.5016) and effusion score (r, 0.6817).
Conclusions and Clinical Relevance—Assessment of the acute inflammatory process by measurement of PGE2 concentrations in synovial fluid may be correlated with the amount of pain or lameness in dogs. (Am J Vet Res 2004;65:1269–1275)
Abstract
Objective—To determine whether decreases in peak vertical force of the hind limb after transection of the cranial cruciate ligament (CrCL) would be indicative of medial meniscal damage in dogs.
Animals—39 purpose-bred adult male Walker Hounds.
Procedure—The right CrCL was transected arthroscopically. Force plate measurements of the right hind limb were made prior to and 2, 4, 10, and 18 weeks after transection of the CrCL. Only dogs with ≥ 10% decreases in peak vertical force after week 2 were considered to have potential meniscal damage. Dogs that did not have ≥ 10% decreases in peak vertical force at any time point after week 2 were assigned to group 1. Group 2 dogs had ≥ 10% decreases in peak vertical force from weeks 2 to 4 only. Group 3 and 4 dogs had ≥ 10% decreases in peak vertical force from weeks 4 to 10 only or from weeks 10 to 18 only, respectively. Damage to menisci and articular cartilage was graded at week 18, and grades for groups 2 to 4 were compared with those of group 1.
Results—The percentage change in peak vertical force and impulse area was significantly different in groups 2 (n = 4), 3 (4), and 4 (4) at the end of each measurement period (weeks 4, 10, and 18, respectively) than in group 1 (27). The meniscal grade for groups 2 to 4 was significantly higher than for group 1. A ≥ 10% decrease in peak vertical force had sensitivity of 52% and accuracy of 72% for identifying dogs with moderate to severe medial meniscal damage.
Conclusions and Clinical Relevance—In dogs with transected or ruptured CrCLs, force plate analysis can detect acute exacerbation of lameness, which may be the result of secondary meniscal damage, and provide an objective noninvasive technique that delineates the temporal pattern of medial meniscal injury. ( Am J Vet Res 2005;66:156–163)
Abstract
Objective—To compare articular cartilage from horses with naturally developing osteochondrosis (OC) with normal articular cartilage and healing cartilage obtained from horses with experimentally induced osteochondral fractures.
Sample Population—109 specimens of articular cartilage from 78 horses.
Procedure—Morphologic characteristics, proteoglycan (PG), and type II collagen were analyzed in articular cartilage of OC specimens (group 1), matched healing cartilage obtained 40 days after experimentally induced osteochondral fractures (group 2), and matched normal cartilage from the same sites (group 3).
Results—79 specimens of OC cartilage were obtained from horses. Ex vivo PG synthesis was significantly greater in the femoral cartilage, compared with synthesis in the tibial cartilage, and significantly greater for groups 1 and 2, compared with group 3. For groups 1 and 2, femoral fragments had significantly greater PG content, compared with PG content in tibial fragments. Keratan sulfate content was significantly less in group 3, compared with groups 1 and 2. Cartilage from the OC specimens had loss of structural architecture. The OC tissue bed stained positive for chondroitin sulfate and type II collagen, but the fracture bed did not.
Conclusions and Clinical Relevance—Our analyses could not distinguish articular cartilage from horses with OC and a healing fracture. Both resembled an anabolic, reparative process. Immunohistochemical analysis suggested a chondromyxoid tissue in the OC bed that was morphologically similar to fibrous tissue but phenotypically resembled hyaline cartilage. Thus, tissue in the OC bed may be degenerative cartilage, whereas tissue in the fracture bed may be reparative fibrous callus. (Am J Vet Res 2005;66:1881–1890)
Abstract
Objective—To assess clinical, radiographic, histologic, and biochemical effects of sodium pentosan polysulfate (NaPPS) administered IM for treatment of experimentally induced osteoarthritis in horses.
Animals—18 horses.
Procedures—Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. Nine horses received NaPPS (3 mg/kg, IM) on study days 15, 22, 29, and 36. Nine control horses received the same volume of saline (0.9% NaCl) solution IM on study days 15, 22, 29, and 36. Clinical, radiographic, gross, histologic, histochemical, and biochemical findings as well as findings of synovial fluid analysis were evaluated.
Results—No adverse treatment-related events were detected. Induced osteoarthritis caused a substantial increase in lameness, response to flexion, joint effusion, radiographic findings, synovial membrane inflammation, and articular cartilage fibrillation. Articular cartilage fibrillation was substantially reduced by NaPPS treatment, and concentrations of chondroitin sulfate 846 epitope were significantly increased in the synovial fluid of osteoarthritic and nonosteoarthritic joints of treated horses.
Conclusions and Clinical Relevance—Results indicated that NaPPS has some beneficial disease-modifying effects and may be a therapeutic option for osteoarthritis in horses.
Abstract
OBJECTIVE To evaluate the efficacy of IV administration of a product containing hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses.
ANIMALS 32 healthy 2- to 5-year-old horses.
PROCEDURES The study involved 2 portions. To evaluate prophylactic efficacy of the test product, horses received 5 mL of the product (n = 8) or saline (0.9% NaCl) solution (8; placebo) IV every fifth day, starting on day 0 (when osteoarthritis was induced in the middle carpal joint of 1 forelimb) and ending on day 70. To evaluate treatment efficacy, horses received either the product or placebo (n = 8/treatment) on days 16, 23, 30, 37, and 44 after osteoarthritis induction. Clinical, diagnostic imaging, synovial fluid, gross anatomic, and histologic evaluations and other tests were performed. Results of each study portion were compared between treatment groups.
RESULTS Limb flexion and radiographic findings were significantly worse for horses that received the test product in the prophylactic efficacy portion than for placebo-treated horses or product-treated horses in the treatment efficacy portion. In the prophylactic efficacy portion, significantly less articular cartilage erosion was identified in product-treated versus placebo-treated horses. In the treatment efficacy portion, joints of product-treated horses had a greater degree of bone edema identified via MRI than did joints of placebo-treated horses but fewer microscopic articular cartilage abnormalities.
CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that caution should be used when administering the evaluated product IV to horses, particularly when administering it prophylactically, as it may have no benefit or may even cause harm.
Abstract
Objective—To investigate the influence of early conditioning exercise on the development of gross cartilage defects and swelling behavior of cartilage extracellular matrix (ECM) in the midcarpal joint of horses.
Animals—12 Thoroughbreds.
Procedures—6 horses underwent early conditioning exercise from birth to 18 months of age (CONDEX group), and 6 horses were used as control animals (PASTEX group). The horses were euthanized at 18 months of age, and the midcarpal joints were harvested. Gross defects of the cartilage surface were classified and mapped. Opposing surfaces of the third and radial carpal bones were used to quantify swelling behavior of the cartilage ECM.
Results—A wide range of gross defects was detected in the cartilage on the opposing surfaces of the bones of the midcarpal joint; however, there was no significant difference between the CONDEX and PASTEX groups. Similarly, no significant difference in swelling behavior of the cartilage ECM was evident between the CONDEX and PASTEX groups.
Conclusions and Clinical Relevance—In the study reported here, we did not detect negative influences of early conditioning exercise on the prevalence of gross defects in cartilage of the midcarpal joint or the quality of the cartilage ECM as defined by swelling behavior. These results suggested that early conditioning exercise may be used without negative consequences for the midcarpal joint and the cartilage ECM of the third and radial carpal bones.
Abstract
Objective—To describe and measure histologic features of midcarpal joint cartilage defects in Thoroughbreds and evaluate the influence of early conditioning exercise on defect development.
Sample—24 midcarpal joints from twelve 18-month-old Thoroughbreds.
Procedures—Midcarpal joints from 12 horses (6 exercised spontaneously at pasture only and 6 given additional conditioning exercise beginning at a mean age of 3 weeks were evaluated. Gross cartilage defects were assessed histologically. Third and radial carpal bones were categorized with regard to the presence or absence of calcified cartilage (CC) abnormalities at the dorsoproximal and dorsodistal articular surfaces, respectively; histomorphometric assessment and statistical analysis were conducted for the third carpal bone.
Results—Number and severity of defects did not appear different between exercise groups. Nine third or radial carpal bones had thickened CC with microcracks, matrix and osteochondral junction changes, and increased vascularity, without histologic changes in the hyaline cartilage. Third carpal bones with CC abnormalities had significantly thicker CC (452 vs 228 μm) than did those without CC abnormalities in the evaluated region. However, in the same region, there were no significant differences in hyaline cartilage thickness (681 vs 603 μm), vascular channel area in the subchondral bone (624,894 vs 490,320 μm2), or number of vascular channels (15.9 vs 18.0).
Conclusions and Clinical Relevance—Early exercise did not appear to influence the distribution or severity of cartilage defects in the midcarpal joint. Calcified cartilage abnormalities beneath the undisrupted hyaline cartilage in the dorsoproximal aspect of the third carpal bone may represent the first changes in the pathogenesis of midcarpal osteochondral disease.
Abstract
Objective—To investigate histomorphometric changes in the cartilage and subchondral bone of the third carpal bone associated with conditioning exercise in young Thoroughbreds.
Animals—Nine 18-month-old Thoroughbreds.
Procedures—Both third carpal bones of 9 horses (4 exercised spontaneously at pasture only and 5 given additional conditioning exercise beginning at a mean age of 3 weeks) were evaluated. Histomorphometric variables (hyaline and calcified cartilage thickness and collagen orientation; vascular channel area, number, and orientation; and osteochondral junction rugosity) of the third carpal bone, sampled at 4 dorsopalmar sites in the radial facet, were compared between the exercised and nonexercised groups.
Results—The vascular channel area measured at the 4 dorsopalmar sites was larger in the exercised group than in the control group, but none of the variables were significantly different between groups. Both groups had significant site-specific variations in all measured variables. Most importantly, the vascular channel area was highest in the most dorsal aspect.
Conclusions and Clinical Relevance—Results suggested that the mild exercise imposed in both groups during the developmental period appeared to be associated with an increase in the vascular channel area beneath the calcified cartilage layer in the third carpal bone. This increased vascular channel area could also be associated with high stress in the dorsal aspect of the radial facet, a region that is known to be vulnerable to osteochondral fragmentation.
Abstract
Objective—To develop an antibody that specifically recognizes collagenase-cleaved type-II collagen in equine articular cartilage.
Sample Population—Cartilage specimens from horses euthanatized for problems unrelated to the musculoskeletal system.
Procedure—A peptide was synthesized representing the carboxy- (C-) terminus (neoepitope) of the equine type-II collagen fragment created by mammalian collagenases. This peptide was used to produce a polyclonal antibody, characterized by western analysis for reactivity to native and collagenase-cleaved equine collagens. The antibody was evaluated as an antineoepitope antibody by ELISA, using peptides ± an amino acid at the C-terminus of the immunizing peptide. Collagen cleavage was assayed from equine articular cartilage cultured with interleukin-1 (IL-1), ± a synthetic MMP inhibitor, BAY 12-9566. Cartilage specimens from osteoarthritic and nonarthritic joints were compared for antibody staining.
Results—An antibody, 234CEQ, recognized only collagenase- generated 3/4-length fragments of equine type-II collagen. This was a true antineoepitope antibody, as altering the C-terminus of the immunizing peptide significantly decreased competition for binding in an inhibition ELISA. The IL-1-induced release of type-II collagen fragments from articular cartilage was prevented with the MMP inhibitor. Cartilage from an osteoarthritic joint of a horse had increased staining with the 234CEQ antibody, compared with normal articular cartilage.
Conclusions and Clinical Relevance—We generated an antineoepitope antibody recognizing collagenase- cleaved type-II collagen of horses. This antibody detects increases in type-II collagen cleavage in diseased equine articular cartilage. The 234CEQ antibody has the potential to aid in the early diagnosis of arthritis and to monitor treatment responses. (Am J Vet Res 2001;62:1031–1039)
Abstract
Objective—To determine whether serum concentrations of biomarkers of skeletal metabolism can, in conjunction with radiographic evaluation, indicate severity of osteochondrosis in developing horses.
Animals—43 Dutch Warmblood foals with varying severity of osteochondrosis.
Procedure—24 foals were monitored for 5 months and 19 foals were monitored for 11 months. Monthly radiographs of femoropatellar-femorotibial and tibiotarsal joints were graded for osteochondral abnormalities. Serial blood samples were assayed for 8 cartilage and bone biomarkers. At the end of the monitoring period, foals were examined for macroscopic osteochondrosis lesions.
Results—Temporal relationships were evident between certain serum biomarkers and osteochondrosis severity in foals during their first year. Biomarkers of collagen degradation (collagenasegenerated neoepitopes of type-II collagen fragments, type-I and -II collagen fragments [COL2-3/4Cshort], and cross-linked telopeptide fragments of type-I collagen) and bone mineralization (osteocalcin) were positive indicators of osteochondrosis severity at 5 months of age. In foals with lesions at 11 months of age, osteochondrosis severity correlated negatively with COL2-3/4Cshort and osteocalcin and positively with C-propeptide of type-II procollagen (CPII), a collagen synthesis marker. Radiographic grading of osteochondrosis lesions significantly correlated with macroscopic osteochondrosis severity score at both ages and was strongest when combined with osteocalcin at 5 months and CPII at 11 months.
Conclusions and Clinical Relevance—The ability of serum biomarkers to indicate osteochondrosis severity appears to depend on stage of disease and is strengthened with radiography. In older foals with more permanent lesions, osteochondrosis severity is significantly related to biomarker concentrations of decreased bone formation and increased cartilage synthesis. (Am J Vet Res 2004;65:143–150)
