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Peter Muir - One of the best experts on this subject based on the ideXlab platform.
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radiographic and magnetic resonance imaging predicts severity of cruciate ligament fiber damage and synovitis in dogs with cranial cruciate ligament rupture
PLOS ONE, 2017Co-Authors: Susannah J. Sample, Susan L Schaefer, Jason A. Bleedorn, Gerianne Holzman, Eric C. Hans, Nicola Volstad, Molly A Racette, Kenneth R. Waller, Walter F. Block, Peter MuirAbstract:Cruciate ligament rupture (CR) and associated osteoarthritis (OA) is a common condition in dogs. Dogs frequently develop a second contralateral CR. This study tested the hypothesis that the degree of Stifle synovitis and cranial cruciate ligament (CrCL) matrix damage in dogs with CR is correlated with non-invasive diagnostic tests, including magnetic resonance (MR) imaging. We conducted a prospective cohort study of 29 client-owned dogs with an unstable Stifle due to complete CR and stable contralateral Stifle with partial CR. We evaluated correlation of Stifle synovitis and CrCL fiber damage with diagnostic tests including bilateral Stifle radiographs, 3.0 Tesla MR imaging, and bilateral Stifle arthroscopy. Histologic grading and immunohistochemical staining for CD3+ T lymphocytes, TRAP+ activated macrophages and Factor VIII+ blood vessels in bilateral Stifle synovial biopsies were also performed. Serum and synovial fluid concentrations of C-reactive protein (CRP) and carboxy-terminal telopeptide of type I collagen (ICTP), and synovial total nucleated cell count were determined. Synovitis was increased in complete CR Stifles relative to partial CR Stifles (P<0.0001), although total nucleated cell count in synovial fluid was increased in partial CR Stifles (P<0.01). In partial CR Stifles, we found that 3D Fast Spin Echo Cube CrCL signal intensity was correlated with histologic synovitis (SR = 0.50, P<0.01) and that radiographic OA was correlated with CrCL fiber damage assessed arthroscopically (SR = 0.61, P<0.001). Taken together, results of this study show that clinical diagnostic tests predict severity of Stifle synovitis and cruciate ligament matrix damage in stable partial CR Stifles. These data support use of client-owned dogs with unilateral complete CR and contralateral partial CR as a clinical trial model for investigation of disease-modifying therapy for partial CR.
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autologous bone marrow derived mesenchymal stem cells modulate molecular markers of inflammation in dogs with cruciate ligament rupture
PLOS ONE, 2016Co-Authors: Peter Muir, Susan L Schaefer, Gerianne Holzman, Eric C. Hans, Nicola Volstad, Susannah J. Sample, Debra D. Bloom, Molly A Racette, Caitlin M Heaton, Jason A. BleedornAbstract:Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated Stifle osteoarthritis (OA) is an important veterinary health problem. CR causes Stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and Stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR Stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR Stifle. Blood (entry, 4 and 8 weeks) and Stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR Stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both Stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR Stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and Stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the Stifle joint inflammatory response associated with cranial cruciate ligament matrix degeneration or damage.
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Radiographic synovial effusion and osteophytosis in dogs with unilateral complete cruciate ligament rupture and contralateral partial cruciate ligament rupture.
2016Co-Authors: Peter Muir, Susan L Schaefer, Gerianne Holzman, Eric C. Hans, Molly Racette, Nicola Volstad, Susannah J. Sample, Caitlin Heaton, Debra D. Bloom, Jason A. BleedornAbstract:Orthogonal Stifle radiographic views of the unstable Stifle with complete cruciate ligament rupture (CR) (A,B) and the contralateral stable Stifle with partial CR (C,D) in a four old mixed breed dog at trial entry. Synovial effusion with compression of the infrapatellar fat pat and caudal bulging of the joint capsule is evident in both Stifles. Peri-articular osteophytosis is present in both Stifles and is particularly evident on the distal pole of the patella, the trochlea ridges of the distal femur, and the margins of the tibial plateau. Osteophytosis is more severe in the Stifle with complete CR in this dog. Overall, at diagnosis and trial entry, Stifle synovial effusion (P
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radiographic risk factors for contralateral rupture in dogs with unilateral cranial cruciate ligament rupture
PLOS ONE, 2014Co-Authors: Connie Chuang, Susan L Schaefer, Megan A Ramaker, Sirjaut Kaur, Rebecca A Csomos, Kevin T Kroner, Jason A. Bleedorn, Peter MuirAbstract:Background Complete cranial cruciate ligament rupture (CR) is a common cause of pelvic limb lameness in dogs. Dogs with unilateral CR often develop contralateral CR over time. Although radiographic signs of contralateral Stifle joint osteoarthritis (OA) influence risk of subsequent contralateral CR, this risk has not been studied in detail. Methodology/Principal Findings We conducted a retrospective longitudinal cohort study of client-owned dogs with unilateral CR to determine how severity of radiographic Stifle synovial effusion and osteophytosis influence risk of contralateral CR over time. Detailed survival analysis was performed for a cohort of 85 dogs after case filtering of an initial sample population of 513 dogs. This population was stratified based on radiographic severity of synovial effusion (graded on a scale of 0, 1, and 2) and severity of osteophytosis (graded on a scale of 0, 1, 2, and 3) of both index and contralateral Stifle joints using a reproducible scoring method. Severity of osteophytosis in the index and contralateral Stifles was significantly correlated. Rupture of the contralateral cranial cruciate ligament was significantly influenced by radiographic OA in both the index and contralateral Stifles at diagnosis. Odds ratio for development of contralateral CR in dogs with severe contralateral radiographic Stifle effusion was 13.4 at one year after diagnosis and 11.4 at two years. Odds ratio for development of contralateral CR in dogs with severe contralateral osteophytosis was 9.9 at one year after diagnosis. These odds ratios were associated with decreased time to contralateral CR. Breed, age, body weight, gender, and tibial plateau angle did not significantly influence time to contralateral CR. Conclusion Subsequent contralateral CR is significantly influenced by severity of radiographic Stifle effusion and osteophytosis in the contralateral Stifle, suggesting that synovitis and arthritic joint degeneration are significant factors in the disease mechanism underlying the arthropathy.
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Lateral radiographic images of the Stifle (A–C).
2014Co-Authors: Jeffrey P. Little, Susan L Schaefer, Megan A Ramaker, Jason A. Bleedorn, Zhengling Hao, Brian J. Sutherland, Ruth Sullivan, Vicki L. Kalscheur, Peter MuirAbstract:(A) Index Stifle with marked osteophytosis and effusion. (B) Contralateral Stifle with mild osteophytosis and moderate effusion. (C) Contralateral Stifle with no radiographic osteophytosis and mild effusion (white arrow). (D) Same contralateral Stifle from image ‘C’ with minimal radiographic changes demonstrating obvious synovitis and fraying of the cranial cruciate ligament (narrow black arrow) and inflammation of the synovium overlying the caudal cruciate ligament (broad black arrowhead).
Susan L Schaefer - One of the best experts on this subject based on the ideXlab platform.
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use of a platelet rich plasma collagen scaffold as a bioenhanced repair treatment for management of partial cruciate ligament rupture in dogs
PLOS ONE, 2018Co-Authors: Susannah J. Sample, Susan L Schaefer, Jason A. Bleedorn, Zhengling Hao, Jeffrey P. Little, Eric C. Hans, Nicola Volstad, Molly A Racette, Kenneth R. Waller, Walter F. BlockAbstract:Dogs are commonly affected with cruciate ligament rupture (CR) and associated osteoarthritis (OA), and frequently develop a second contralateral CR. Platelet rich plasma (PRP) is a component of whole blood that contains numerous growth factors, which in combination with a collagen scaffold may act to promote bioenhanced primary repair of ligament. This study tested the hypothesis that treatment of partial stable CR Stifles with an intra-articular collagen scaffold and PRP would decrease the disease progression, synovitis and risk of complete CR over a 12-month study period. We conducted a prospective cohort study of 29 client-owned dogs with an unstable Stifle due to complete CR and stable contralateral Stifle with partial CR. All dogs were treated with tibial plateau leveling osteotomy (TPLO) on the unstable Stifle and a single intra-articular application of PRP-collagen in the stable partial CR Stifle. Dogs were evaluated at the time of diagnosis, and at 10-weeks and 12-months after treatment. We evaluated correlation between both development of complete CR and time to complete CR with diagnostic tests including bilateral Stifle radiographs, 3.0 Tesla magnetic resonance (MR) imaging, and bilateral Stifle arthroscopy. Additionally, histologic evaluation of synovial biopsies, C-reactive protein (CRP) concentrations in serum and synovial fluid, and synovial total nucleated cell count, were determined. Results indicated that a single application of PRP-collagen in partial CR Stifles of client owned dogs is not an effective disease-modifying therapy for the prevention of progression to complete CR. Radiographic effusion, arthroscopic evaluation of cranial cruciate ligament (CrCL) damage, and MR assessment of ligament fiber tearing in partial CR Stifles correlated with progression to complete CR over the 12-month follow-up period. We determined that the best predictive model for development of complete CR in PRP-collagen treated partial CR Stifles included variables from multiple diagnostic modalities.
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radiographic and magnetic resonance imaging predicts severity of cruciate ligament fiber damage and synovitis in dogs with cranial cruciate ligament rupture
PLOS ONE, 2017Co-Authors: Susannah J. Sample, Susan L Schaefer, Jason A. Bleedorn, Gerianne Holzman, Eric C. Hans, Nicola Volstad, Molly A Racette, Kenneth R. Waller, Walter F. Block, Peter MuirAbstract:Cruciate ligament rupture (CR) and associated osteoarthritis (OA) is a common condition in dogs. Dogs frequently develop a second contralateral CR. This study tested the hypothesis that the degree of Stifle synovitis and cranial cruciate ligament (CrCL) matrix damage in dogs with CR is correlated with non-invasive diagnostic tests, including magnetic resonance (MR) imaging. We conducted a prospective cohort study of 29 client-owned dogs with an unstable Stifle due to complete CR and stable contralateral Stifle with partial CR. We evaluated correlation of Stifle synovitis and CrCL fiber damage with diagnostic tests including bilateral Stifle radiographs, 3.0 Tesla MR imaging, and bilateral Stifle arthroscopy. Histologic grading and immunohistochemical staining for CD3+ T lymphocytes, TRAP+ activated macrophages and Factor VIII+ blood vessels in bilateral Stifle synovial biopsies were also performed. Serum and synovial fluid concentrations of C-reactive protein (CRP) and carboxy-terminal telopeptide of type I collagen (ICTP), and synovial total nucleated cell count were determined. Synovitis was increased in complete CR Stifles relative to partial CR Stifles (P<0.0001), although total nucleated cell count in synovial fluid was increased in partial CR Stifles (P<0.01). In partial CR Stifles, we found that 3D Fast Spin Echo Cube CrCL signal intensity was correlated with histologic synovitis (SR = 0.50, P<0.01) and that radiographic OA was correlated with CrCL fiber damage assessed arthroscopically (SR = 0.61, P<0.001). Taken together, results of this study show that clinical diagnostic tests predict severity of Stifle synovitis and cruciate ligament matrix damage in stable partial CR Stifles. These data support use of client-owned dogs with unilateral complete CR and contralateral partial CR as a clinical trial model for investigation of disease-modifying therapy for partial CR.
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Relationships between diagnostic variables in complete and partial cruciate rupture Stifles to evaluate patterns of correlation between markers.
2017Co-Authors: Susannah J. Sample, Susan L Schaefer, Jason A. Bleedorn, Gerianne Holzman, Zhengling Hao, Eric C. Hans, Nicola Volstad, Molly A Racette, Kenneth R. Waller, Walter F. BlockAbstract:(A) In the complete CR Stifle, correlations formed three clusters. Several inflammation markers were positively correlated with Synovial and Serum CRP concentrations, suggesting that inflammation promotes collagen degradation within affected Stifles. Serum CRP was also positively correlated with histologic inflammation. In a second cluster, Radiographic effusion and OA were positively correlated with arthroscopic synovitis variables. In a third cluster, numbers of CD3+ lymphocytes were positively correlated with numbers of TRAP+ macrophages and neutrophils. (B) In the partial CR Stifle, a larger number of positive correlations were identified that formed four clusters. Suppurative inflammation was positively correlated with CrCL ligament volume, assessed by MR imaging, and functional length of the ligament, suggesting that acute inflammation is related to ligament edema and loss of mechanical properties. In a second cluster, synovial and serum CRP concentrations were correlated with Stifle TNCC, indicating that biochemical markers of inflammation correlate with inflammatory cell counts. In a third cluster, the synovial to serum CRP ratio was positively correlated several histologic markers of inflammation, suggesting that the synovial to serum CRP ratio is likely a clinically useful marker of Stifle synovitis. In a fourth cluster, arthroscopic variables of inflammation were correlated with MR imaging measures of ligament fluid content, as measured by grayscale value, suggesting that early in the CR condition, synovitis may result in increased ligament fluid content. Abbreviations: TAS, Total Arthroscopic Score; ACVAS, Arthroscopic CrCL Fiber Damage Visual Analog Scale (VAS) score; AVAS, Arthroscopic Synovitis VAS score; CD3, CD3+ T Lymphocyte Grade; CrCLD, Radiographic length of CrCL normalized to patellar length; CRPR, C-reactive Protein (CRP) serum to synovial fluid ratio; FSEG, MR imaging CrCL FSE Grayscale; FSEV, MR imaging CrCL FSE Volume; FVIII, Synovial Factor VIII+ Vessel Grade; FVIIIVAS, Synovial Factor VIII+ Vessel VAS; Hgrade, Histologic Synovitis Grade; HVAS, Histologic Synovitis VAS Score; ICTPR, pyridinoline cross-lined carboxy-terminal telopeptide of type I collagen (ICTP) serum to synovial fluid ratio; JCRP, Synovial fluid CRP; JICTP, Synovial fluid ICTP; RADE, Radiographic Effusion score; RADOA, Radiographic OA score; SCRP, Serum C-Reactive Protein; SICTP, Serum ICTP; Supp, Suppurative Inflammation Grade; T1, MR imaging CrCL T1 Enhancement; TNCC, Synovial fluid total nucleated cell count; TPA, Tibial Plateau Angle; TRAP, TRAP+ Macrophage Grade; VIPRV, MR imaging CrCL VIPR Volume; VIPRG, MR imaging CrCL VIPR Grayscale.
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Radiographic and magnetic resonance imaging predicts severity of cruciate ligament fiber damage and synovitis in dogs with cranial cruciate ligament rupture
2017Co-Authors: Susannah J. Sample, Susan L Schaefer, Jason A. Bleedorn, Gerianne Holzman, Zhengling Hao, Eric C. Hans, Nicola Volstad, Molly A Racette, Kenneth R. Waller, Walter F. BlockAbstract:Cruciate ligament rupture (CR) and associated osteoarthritis (OA) is a common condition in dogs. Dogs frequently develop a second contralateral CR. This study tested the hypothesis that the degree of Stifle synovitis and cranial cruciate ligament (CrCL) matrix damage in dogs with CR is correlated with non-invasive diagnostic tests, including magnetic resonance (MR) imaging. We conducted a prospective cohort study of 29 client-owned dogs with an unstable Stifle due to complete CR and stable contralateral Stifle with partial CR. We evaluated correlation of Stifle synovitis and CrCL fiber damage with diagnostic tests including bilateral Stifle radiographs, 3.0 Tesla MR imaging, and bilateral Stifle arthroscopy. Histologic grading and immunohistochemical staining for CD3+ T lymphocytes, TRAP+ activated macrophages and Factor VIII+ blood vessels in bilateral Stifle synovial biopsies were also performed. Serum and synovial fluid concentrations of C-reactive protein (CRP) and carboxy-terminal telopeptide of type I collagen (ICTP), and synovial total nucleated cell count were determined. Synovitis was increased in complete CR Stifles relative to partial CR Stifles (P
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autologous bone marrow derived mesenchymal stem cells modulate molecular markers of inflammation in dogs with cruciate ligament rupture
PLOS ONE, 2016Co-Authors: Peter Muir, Susan L Schaefer, Gerianne Holzman, Eric C. Hans, Nicola Volstad, Susannah J. Sample, Debra D. Bloom, Molly A Racette, Caitlin M Heaton, Jason A. BleedornAbstract:Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated Stifle osteoarthritis (OA) is an important veterinary health problem. CR causes Stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and Stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR Stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR Stifle. Blood (entry, 4 and 8 weeks) and Stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR Stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both Stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR Stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and Stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the Stifle joint inflammatory response associated with cranial cruciate ligament matrix degeneration or damage.
Jason A. Bleedorn - One of the best experts on this subject based on the ideXlab platform.
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use of a platelet rich plasma collagen scaffold as a bioenhanced repair treatment for management of partial cruciate ligament rupture in dogs
PLOS ONE, 2018Co-Authors: Susannah J. Sample, Susan L Schaefer, Jason A. Bleedorn, Zhengling Hao, Jeffrey P. Little, Eric C. Hans, Nicola Volstad, Molly A Racette, Kenneth R. Waller, Walter F. BlockAbstract:Dogs are commonly affected with cruciate ligament rupture (CR) and associated osteoarthritis (OA), and frequently develop a second contralateral CR. Platelet rich plasma (PRP) is a component of whole blood that contains numerous growth factors, which in combination with a collagen scaffold may act to promote bioenhanced primary repair of ligament. This study tested the hypothesis that treatment of partial stable CR Stifles with an intra-articular collagen scaffold and PRP would decrease the disease progression, synovitis and risk of complete CR over a 12-month study period. We conducted a prospective cohort study of 29 client-owned dogs with an unstable Stifle due to complete CR and stable contralateral Stifle with partial CR. All dogs were treated with tibial plateau leveling osteotomy (TPLO) on the unstable Stifle and a single intra-articular application of PRP-collagen in the stable partial CR Stifle. Dogs were evaluated at the time of diagnosis, and at 10-weeks and 12-months after treatment. We evaluated correlation between both development of complete CR and time to complete CR with diagnostic tests including bilateral Stifle radiographs, 3.0 Tesla magnetic resonance (MR) imaging, and bilateral Stifle arthroscopy. Additionally, histologic evaluation of synovial biopsies, C-reactive protein (CRP) concentrations in serum and synovial fluid, and synovial total nucleated cell count, were determined. Results indicated that a single application of PRP-collagen in partial CR Stifles of client owned dogs is not an effective disease-modifying therapy for the prevention of progression to complete CR. Radiographic effusion, arthroscopic evaluation of cranial cruciate ligament (CrCL) damage, and MR assessment of ligament fiber tearing in partial CR Stifles correlated with progression to complete CR over the 12-month follow-up period. We determined that the best predictive model for development of complete CR in PRP-collagen treated partial CR Stifles included variables from multiple diagnostic modalities.
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radiographic and magnetic resonance imaging predicts severity of cruciate ligament fiber damage and synovitis in dogs with cranial cruciate ligament rupture
PLOS ONE, 2017Co-Authors: Susannah J. Sample, Susan L Schaefer, Jason A. Bleedorn, Gerianne Holzman, Eric C. Hans, Nicola Volstad, Molly A Racette, Kenneth R. Waller, Walter F. Block, Peter MuirAbstract:Cruciate ligament rupture (CR) and associated osteoarthritis (OA) is a common condition in dogs. Dogs frequently develop a second contralateral CR. This study tested the hypothesis that the degree of Stifle synovitis and cranial cruciate ligament (CrCL) matrix damage in dogs with CR is correlated with non-invasive diagnostic tests, including magnetic resonance (MR) imaging. We conducted a prospective cohort study of 29 client-owned dogs with an unstable Stifle due to complete CR and stable contralateral Stifle with partial CR. We evaluated correlation of Stifle synovitis and CrCL fiber damage with diagnostic tests including bilateral Stifle radiographs, 3.0 Tesla MR imaging, and bilateral Stifle arthroscopy. Histologic grading and immunohistochemical staining for CD3+ T lymphocytes, TRAP+ activated macrophages and Factor VIII+ blood vessels in bilateral Stifle synovial biopsies were also performed. Serum and synovial fluid concentrations of C-reactive protein (CRP) and carboxy-terminal telopeptide of type I collagen (ICTP), and synovial total nucleated cell count were determined. Synovitis was increased in complete CR Stifles relative to partial CR Stifles (P<0.0001), although total nucleated cell count in synovial fluid was increased in partial CR Stifles (P<0.01). In partial CR Stifles, we found that 3D Fast Spin Echo Cube CrCL signal intensity was correlated with histologic synovitis (SR = 0.50, P<0.01) and that radiographic OA was correlated with CrCL fiber damage assessed arthroscopically (SR = 0.61, P<0.001). Taken together, results of this study show that clinical diagnostic tests predict severity of Stifle synovitis and cruciate ligament matrix damage in stable partial CR Stifles. These data support use of client-owned dogs with unilateral complete CR and contralateral partial CR as a clinical trial model for investigation of disease-modifying therapy for partial CR.
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Relationships between diagnostic variables in complete and partial cruciate rupture Stifles to evaluate patterns of correlation between markers.
2017Co-Authors: Susannah J. Sample, Susan L Schaefer, Jason A. Bleedorn, Gerianne Holzman, Zhengling Hao, Eric C. Hans, Nicola Volstad, Molly A Racette, Kenneth R. Waller, Walter F. BlockAbstract:(A) In the complete CR Stifle, correlations formed three clusters. Several inflammation markers were positively correlated with Synovial and Serum CRP concentrations, suggesting that inflammation promotes collagen degradation within affected Stifles. Serum CRP was also positively correlated with histologic inflammation. In a second cluster, Radiographic effusion and OA were positively correlated with arthroscopic synovitis variables. In a third cluster, numbers of CD3+ lymphocytes were positively correlated with numbers of TRAP+ macrophages and neutrophils. (B) In the partial CR Stifle, a larger number of positive correlations were identified that formed four clusters. Suppurative inflammation was positively correlated with CrCL ligament volume, assessed by MR imaging, and functional length of the ligament, suggesting that acute inflammation is related to ligament edema and loss of mechanical properties. In a second cluster, synovial and serum CRP concentrations were correlated with Stifle TNCC, indicating that biochemical markers of inflammation correlate with inflammatory cell counts. In a third cluster, the synovial to serum CRP ratio was positively correlated several histologic markers of inflammation, suggesting that the synovial to serum CRP ratio is likely a clinically useful marker of Stifle synovitis. In a fourth cluster, arthroscopic variables of inflammation were correlated with MR imaging measures of ligament fluid content, as measured by grayscale value, suggesting that early in the CR condition, synovitis may result in increased ligament fluid content. Abbreviations: TAS, Total Arthroscopic Score; ACVAS, Arthroscopic CrCL Fiber Damage Visual Analog Scale (VAS) score; AVAS, Arthroscopic Synovitis VAS score; CD3, CD3+ T Lymphocyte Grade; CrCLD, Radiographic length of CrCL normalized to patellar length; CRPR, C-reactive Protein (CRP) serum to synovial fluid ratio; FSEG, MR imaging CrCL FSE Grayscale; FSEV, MR imaging CrCL FSE Volume; FVIII, Synovial Factor VIII+ Vessel Grade; FVIIIVAS, Synovial Factor VIII+ Vessel VAS; Hgrade, Histologic Synovitis Grade; HVAS, Histologic Synovitis VAS Score; ICTPR, pyridinoline cross-lined carboxy-terminal telopeptide of type I collagen (ICTP) serum to synovial fluid ratio; JCRP, Synovial fluid CRP; JICTP, Synovial fluid ICTP; RADE, Radiographic Effusion score; RADOA, Radiographic OA score; SCRP, Serum C-Reactive Protein; SICTP, Serum ICTP; Supp, Suppurative Inflammation Grade; T1, MR imaging CrCL T1 Enhancement; TNCC, Synovial fluid total nucleated cell count; TPA, Tibial Plateau Angle; TRAP, TRAP+ Macrophage Grade; VIPRV, MR imaging CrCL VIPR Volume; VIPRG, MR imaging CrCL VIPR Grayscale.
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Radiographic and magnetic resonance imaging predicts severity of cruciate ligament fiber damage and synovitis in dogs with cranial cruciate ligament rupture
2017Co-Authors: Susannah J. Sample, Susan L Schaefer, Jason A. Bleedorn, Gerianne Holzman, Zhengling Hao, Eric C. Hans, Nicola Volstad, Molly A Racette, Kenneth R. Waller, Walter F. BlockAbstract:Cruciate ligament rupture (CR) and associated osteoarthritis (OA) is a common condition in dogs. Dogs frequently develop a second contralateral CR. This study tested the hypothesis that the degree of Stifle synovitis and cranial cruciate ligament (CrCL) matrix damage in dogs with CR is correlated with non-invasive diagnostic tests, including magnetic resonance (MR) imaging. We conducted a prospective cohort study of 29 client-owned dogs with an unstable Stifle due to complete CR and stable contralateral Stifle with partial CR. We evaluated correlation of Stifle synovitis and CrCL fiber damage with diagnostic tests including bilateral Stifle radiographs, 3.0 Tesla MR imaging, and bilateral Stifle arthroscopy. Histologic grading and immunohistochemical staining for CD3+ T lymphocytes, TRAP+ activated macrophages and Factor VIII+ blood vessels in bilateral Stifle synovial biopsies were also performed. Serum and synovial fluid concentrations of C-reactive protein (CRP) and carboxy-terminal telopeptide of type I collagen (ICTP), and synovial total nucleated cell count were determined. Synovitis was increased in complete CR Stifles relative to partial CR Stifles (P
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autologous bone marrow derived mesenchymal stem cells modulate molecular markers of inflammation in dogs with cruciate ligament rupture
PLOS ONE, 2016Co-Authors: Peter Muir, Susan L Schaefer, Gerianne Holzman, Eric C. Hans, Nicola Volstad, Susannah J. Sample, Debra D. Bloom, Molly A Racette, Caitlin M Heaton, Jason A. BleedornAbstract:Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated Stifle osteoarthritis (OA) is an important veterinary health problem. CR causes Stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and Stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR Stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR Stifle. Blood (entry, 4 and 8 weeks) and Stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR Stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both Stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR Stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and Stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the Stifle joint inflammatory response associated with cranial cruciate ligament matrix degeneration or damage.
Steven P. Arnoczky - One of the best experts on this subject based on the ideXlab platform.
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Experimental and Basic Research Studies Three dimensional, radiosteriometric analysis (RSA) of equine Stifle kinematics and articular surface contact: A cadaveric study
2016Co-Authors: S E Halley, Michael Lavagnino, M J Bey, J A Haladik, Steven P. ArnoczkyAbstract:Reasons for performing study: Studies examining the effect of Stifle joint angle on tibial rotation, adduction–abduction angle and articular contact area are lacking. Objectives: To test the hypothesis that tibial rotation, adduction–abduction angle and articular contact area change with Stifle joint angle. Study design: Descriptive study of normal kinematics and articular contact patterns of the equine Stifle through the functional range of motion using 3 dimensional (3D) radiosteriometric analysis (RSA) and equine cadaver Stifles. Methods:Multiple, radiopaque markers were embedded in the distal femur and proximal tibia and sequential, biplanar x-rays captured as the Stifle was passively extended from 110 ° to full extension. Computer-programmed RSAwas used to determine changes in abduction–adduction and internal–external rotation angles of the tibia during Stifle extension as well as articular contact patterns (total area and areas of high contact) through the range of motion. Results: The tibia rotated externally (P<0.001) as the Stifle was extended. Tibial abduction occurred from 110–135 ° of extension (P<0.001) and tibial adduction occurred from 135 ° through full extension (P = 0.009). The centre of joint contact moved cranially on both tibial condyles during extension with the lateral moving a greater distance than the medial (P = 0.003). Articular contact area decreased (P = 0.001) in the medial compartment but not in the lateral compartment (P = 0.285) as the Stifle was extended. The area of highest joint contact increased on the lateral tibial condyle (P<0.001) with extension but decreased (P = 0.001) on the medial tibial condyle. Conclusions: Significant changes occur in tibial rotation, adduction–abduction angle and articular contact area of the equine Stifle through the functional range of motion. Understanding the normal kinematics of the equine Stifle and the relationship between joint positions and articular contact areas ma
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three dimensional radiosteriometric analysis rsa of equine Stifle kinematics and articular surface contact a cadaveric study
Equine Veterinary Journal, 2014Co-Authors: S E Halley, Michael Lavagnino, M J Bey, J A Haladik, Steven P. ArnoczkyAbstract:Summary Reasons for performing study Studies examining the effect of Stifle joint angle on tibial rotation, adduction–abduction angle and articular contact area are lacking. Objectives To test the hypothesis that tibial rotation, adduction–abduction angle and articular contact area change with Stifle joint angle. Study design Descriptive study of normal kinematics and articular contact patterns of the equine Stifle through the functional range of motion using 3 dimensional (3D) radiosteriometric analysis (RSA) and equine cadaver Stifles. Methods Multiple, radiopaque markers were embedded in the distal femur and proximal tibia and sequential, biplanar x-rays captured as the Stifle was passively extended from 110° to full extension. Computer-programmed RSA was used to determine changes in abduction–adduction and internal–external rotation angles of the tibia during Stifle extension as well as articular contact patterns (total area and areas of high contact) through the range of motion. Results The tibia rotated externally (P<0.001) as the Stifle was extended. Tibial abduction occurred from 110–135° of extension (P<0.001) and tibial adduction occurred from 135° through full extension (P = 0.009). The centre of joint contact moved cranially on both tibial condyles during extension with the lateral moving a greater distance than the medial (P = 0.003). Articular contact area decreased (P = 0.001) in the medial compartment but not in the lateral compartment (P = 0.285) as the Stifle was extended. The area of highest joint contact increased on the lateral tibial condyle (P<0.001) with extension but decreased (P = 0.001) on the medial tibial condyle. Conclusions Significant changes occur in tibial rotation, adduction–abduction angle and articular contact area of the equine Stifle through the functional range of motion. Understanding the normal kinematics of the equine Stifle and the relationship between joint positions and articular contact areas may provide important insight into the aetiology and location of common Stifle joint pathologies (articular cartilage and meniscal lesions).
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Stifle extension results in differential tensile forces developing between abaxial and axial components of the cranial meniscotibial ligament of the equine medial meniscus a mechanistic explanation for meniscal tear patterns
Equine Veterinary Journal, 2012Co-Authors: J G Fowlie, Michael Lavagnino, Steven P. Arnoczky, J A StickAbstract:Summary Reason for performing the study: To identify potential functional-anatomical characteristics of the cranial horn attachment of the medial meniscus (MM) that may help explain the pathogenesis of the common tear patterns that have been reported. Hypothesis: Full extension of the Stifle generates a significant increase in tensile forces within the cranial meniscotibial ligament (CrMTL) of the MM, which may predispose this structure to injury. Methods: The effect of femorotibial angle (160°, 150°, 140° and 130°) on tensile forces in the axial and abaxial components of the CrMTL was examined in 6 mature cadaver Stifles using an implantable force probe. Three additional specimens were used to examine the histological structure of the CrMTL and its connection to the cranial horn of the MM. Results: Full extension of the Stifle (160°) resulted in a significantly greater tensile force in the abaxial component of the CrMTL when compared with the axial component (P = 0.001). The tensile force in the abaxial component of the CrMTL increased significantly between 150° and 160° of Stifle extension (P = 0.011). The CrMTL appears to be comprised of 2 functional components, which become more visually distinct as the Stifle is extended. Histologically, these components are separated by a cleft of highly vascularised, less organised connective tissue, which becomes less prominent at the junction of the ligament and the cranial horn of the MM. Conclusion: A 4-fold difference in the tensile forces in the 2 functional components of the CrMTL of the MM was observed with full extension of the Stifle. Potential relevance: The functional anatomy of the CrMTL may place this region at greater risk of injury during hyperextension of the Stifle and, therefore, may provide a mechanistic rationale for the commonly reported meniscal tear patterns in the horse.
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resection of grade iii cranial horn tears of the equine medial meniscus alter the contact forces on medial tibial condyle at full extension an in vitro cadaveric study
Veterinary Surgery, 2011Co-Authors: J G Fowlie, Tristan Maerz, Michael Lavagnino, Steven P. Arnoczky, John A. StickAbstract:Objective To evaluate the magnitude and distribution of joint contact pressure on the medial tibial condyle after grade III cranial horn tears of the medial meniscus. Study Design Experimental study. Animals Cadaveric equine Stifles (n = 6). Methods Cadaveric Stifles were mounted in a materials testing system and electronic pressure sensors were placed between the medial tibial condyle and medial meniscus. Specimens were loaded parallel to the longitudinal axis of the tibia to 1800 N at 130°, 140°, 150°, and 160° Stifle angle. Peak pressure and contact area were recorded from the contact maps. Testing was repeated after surgical creation of a grade III cranial horn tear of the medial meniscus, and after resection of the simulated tear. Results In the intact specimens, a significantly smaller contact area was observed at 160° compared with the other angles (P .05). Resection of the tear resulted in significantly higher peak pressures in the central region of the medial tibial condyle at a Stifle angle of 160° relative to the intact (P = .026) and torn (P = .012) specimens. Conclusions Resection of grade III cranial horn tears in the medial meniscus resulted in a central focal region of increased pressure on the medial tibial condyle at 160° Stifle angle.
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Meniscal translocation and deformation throughout the range of motion of the equine Stifle joint: an in vitro cadaveric study.
Equine veterinary journal, 2010Co-Authors: J G Fowlie, Steven P. Arnoczky, John A. Stick, Anthony PeaseAbstract:Reason for performing study By study of the translocation and deformation of equine menisci throughout the range of motion, it may be possible to identify potential mechanical factors in the pathogenesis of injury to the cranial horn of the medial meniscus. Objective To quantitatively document meniscal translocation and deformation using radiographic and MR imaging, and to evaluate for potential variation between the medial and lateral menisci. Methods Radiographic markers were embedded in the periphery of the menisci in 6 cadaver Stifles. Proximal-distal radiographs were taken at 15° intervals ranging from full flexion (30°) to full extension (160°). Magnetic resonance imaging sequences of 3 additional cadaver Stifles were obtained in axial and sagittal planes at the predetermined Stifle angles. Results A significantly greater overall mean cranial-caudal translocation (1.6 times) of the lateral meniscus relative to the medial was seen from full extension to full flexion (P = 0.002). The cranial horn of the medial meniscus was the least mobile of the 4 horns, yet a significant cranial displacement relative to the cranial horn of the lateral meniscus was seen in the terminal 10° of extension. MRI images revealed a significantly greater axial compressive strain in the cranial horn of the medial meniscus relative to the cranial horn of the lateral meniscus in the terminal 10° of extension (P = 0.017). Conclusion The equine menisci exhibit a cranial-caudal translocation over the tibia throughout the range of motion. While the cranial horn of the medial meniscus is the least mobile of the 4 horns, it undergoes significant cranial translocation and axial compression in the terminal 10° of extension. Potential relevance Hyperextension of the Stifle may place the cranial horn of the medial meniscus at risk of injury and thus explain the higher prevalence of meniscal tears at this location.
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proinflammatory cytokine activities matrix metalloproteinase 3 activity and sulfated glycosaminoglycan content in synovial fluid of dogs with naturally acquired cranial cruciate ligament rupture
Veterinary Surgery, 2006Co-Authors: Yukihiro Fujita, Yasushi Hara, Yoshinori Nezu, Kurt S Schulz, Masahiro TagawaAbstract:OBJECTIVE: To measure and compare activities of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and matrix metalloproteinase-3 (MMP-3); as well as sulfated glycosaminoglycan (S-GAG) content in synovial fluid from dogs with cranial cruciate ligament rupture (CCLR) and dogs with clinically normal Stifles. To determine whether correlations exist between demographic and disease-related variables and these synovial markers. STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs with CCLR (n=23) and Beagles with normal Stifle joints (n=21). METHODS: Synovial fluid activities of proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) were determined by bioassay. MMP-3 activity was measured using fluorogenic substrate. S-GAG contents were determined by dimethylmethylene blue dye-binding assay. Mann-Whitney U-test was used to compare results from CCLR joints with normal controls. Spearman's rank correlation test was used to evaluate associations between demographic and disease-related markers and synovial markers. RESULTS: Mean values for synovial markers were significantly higher in CCLR joints compared with controls. IL-1beta and MMP-3 were positively correlated with lameness duration. CONCLUSIONS: Activities of proinflammatory cytokines, MMP-3 activity and S-GAG contents were significantly elevated in synovial fluid from canine Stifle joints with naturally acquired CCLR. These results indicate that there is joint inflammation and increased release of GAGs into synovial fluid, suggesting that these inflammatory changes are associated with depletion of proteoglycan from articular cartilage. CLINICAL RELEVANCE: Medical and surgical treatments designed to decrease joint inflammation and breakdown of proteoglycans may be of value in the management of CCLR in the dog.
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proinflammatory cytokine activities matrix metalloproteinase 3 activity and sulfated glycosaminoglycan content in synovial fluid of dogs with naturally acquired cranial cruciate ligament rupture
Veterinary Surgery, 2006Co-Authors: Yukihiro Fujita, Yasushi Hara, Yoshinori Nezu, Kurt S Schulz, Masahiro TagawaAbstract:Objective— To measure and compare activities of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-3 (MMP-3); as well as sulfated glycosaminoglycan (S-GAG) content in synovial fluid from dogs with cranial cruciate ligament rupture (CCLR) and dogs with clinically normal Stifles. To determine whether correlations exist between demographic and disease-related variables and these synovial markers. Study Design— Prospective clinical study. Animals— Dogs with CCLR (n=23) and Beagles with normal Stifle joints (n=21). Methods— Synovial fluid activities of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were determined by bioassay. MMP-3 activity was measured using fluorogenic substrate. S-GAG contents were determined by dimethylmethylene blue dye-binding assay. Mann–Whitney U-test was used to compare results from CCLR joints with normal controls. Spearman's rank correlation test was used to evaluate associations between demographic and disease-related markers and synovial markers. Results— Mean values for synovial markers were significantly higher in CCLR joints compared with controls. IL-1β and MMP-3 were positively correlated with lameness duration. Conclusions— Activities of proinflammatory cytokines, MMP-3 activity and S-GAG contents were significantly elevated in synovial fluid from canine Stifle joints with naturally acquired CCLR. These results indicate that there is joint inflammation and increased release of GAGs into synovial fluid, suggesting that these inflammatory changes are associated with depletion of proteoglycan from articular cartilage. Clinical Relevance— Medical and surgical treatments designed to decrease joint inflammation and breakdown of proteoglycans may be of value in the management of CCLR in the dog.
