P A Manley

CSU Mentor, Long Beach, California, United States

Are you P A Manley?

Claim your profile

Publications (61)120.69 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate stifle joints of dogs for synovitis, before development of joint instability and cranial cruciate ligament rupture (CrCLR). Cross-sectional study. Dogs (n = 16) with CrCLR and stable contralateral stifles; 10 control dogs with intact CrCL. Arthritis and tibial translation were graded radiographically. Synovitis severity and cruciate pathology were assessed arthroscopically. Presence of inflammatory cells in synovial membrane biopsies was scored histologically. CrCLR stifle pairs and control stifles were compared. Radiographic evidence of arthritis, cranial tibial translation, and arthroscopic synovitis were increased in unstable stifles, when compared with stable contralateral stifles in CrCLR dogs (P < .05). Arthroscopic synovitis in both joints of CrCLR dogs was increased compared with controls, was correlated with radiographic arthritis (S(R) = 0.71, P < .05), and was present in all stable contralateral stifles. Arthroscopically, 75% of stable stifle joints had CrCL fiber disruption, which correlated with severity of synovitis (S(R) = 0.56, P < .05). Histologic evidence of synovitis was identified in all CrCLR dogs, but was only significantly correlated with arthroscopic observations in stable stifles (r(2) = 0.57, P < .005). Synovitis is an early feature of the CrCLR arthropathy in dogs before development of joint instability clinically. Severity of synovitis is correlated with radiographic arthritis in joints with minimal to no clinically detectable CrCL damage.
    Veterinary Surgery 05/2011; 40(5):531-43. · 1.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The clinical efficacy of oral doxycycline was evaluated in twelve dogs with stifle arthritis and a presumptive diagnosis of early cruciate disease. Doxycycline (2.5-4.5 mg/kg once daily) was administered orally for 3 to 8 weeks. Eight dogs, who presented prior to the treat-ment with clinical signs of 4 weeks or fewer duration (group B), had a good response to doxycycline, whereas four dogs with a longer history of lameness (group A) had a poor response. The follow-up periods ranged from 2 to 12 months after discontinuation of the doxy-cycline treatment (median=6.5 months, 3 months in group A, and 9.5 months in group B). There was a significant correlation between the duration of lameness and the sub-jective grading of clinical improvement. In 68% of these cases of dogs with stifle arthritis (8/12), the oral administration of doxycycline resulted in the improvement of lameness, even after discontinuation of doxycycline. Careful selection of patients based on the duration of their lameness appears to be crucial in order to achieve a positive outcome.
    Veterinary Science Development. 02/2011; 1(1).
  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been proposed that small quantities of microbial material within synovial joints may act as a trigger for development of synovitis. We have previously identified an association between intra-articular bacteria and development of inflammatory stifle arthritis and cranial cruciate ligament rupture (CCLR) in dogs, and now wished to quantify bacterial load and markers of synovitis in dogs with and without stifle arthritis and CCLR. Joint tissues were collected from dogs with CCLR (n=51) and healthy dogs with normal stifles (n=9). Arthritis was assessed radiographically in CCLR dogs. Bacterial load was assessed using qPCR and broad-ranging 16S rRNA primers. qRT-PCR was used to estimate expression of the T lymphocyte antigen receptor (TCR Vβ), CD3ɛ, tartrate-resistant acid phosphatase (TRAP), IL-4, IL-17, and TNF-α genes. Severity of synovitis was assessed histologically. Bacterial load was increased in arthritic stifles, when compared with healthy stifles. Histologic synovitis in arthritic stifles was mononuclear and was significantly correlated with bacterial load (1 of 2 primer sets) (S(R)=0.49, p<0.001). In arthritic stifles, expression of TRAP in synovium was increased relative to healthy stifles. Expression of pro-inflammatory genes was not correlated with bacterial load, histologic inflammation, or radiographic arthritis. Translocation of bacterial material to the canine stifle is related to the presence of joint inflammation. The lack of a strong positive correlation suggests that bacterial load is unlikely to be a primary pro-inflammatory factor. However, dysregulation of immune responses within synovial tissues may be dependent upon an environmental microbial trigger.
    Veterinary Microbiology 09/2010; 148(2-4):308-16. · 3.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An underappreciated cause and effect relationship between environmental bacteria and arthritis may exist. Previously, we found that stifle arthritis in dogs was associated with the presence of environmental bacteria within synovium. Cranial cruciate ligament rupture (CCLR) is often associated with stifle arthritis in dogs. We now wished to determine whether seasonal variation in detection of bacterial material may exist in affected dogs, and to also conduct analyses of both synovium and synovial fluid. We also wished to analyze a larger clone library of the 16S rRNA gene to further understanding of the microbial population in the canine stifle. Synovial biopsies were obtained from 117 affected dogs from January to December 2006. Using PCR, synovium and synovial fluid were tested for Borrelia burgdorferi and Stenotrophomonas maltophilia DNA. Broad-ranging 16S rRNA primers were also used and PCR products were cloned and sequenced for bacterial identification. Overall, 41% of arthritic canine stifle joints contained bacterial DNA. Detection of bacterial DNA in synovial fluid samples was increased, when compared with synovium (p<0.01). Detection rates were highest in the winter and spring and lowest in the summer period, suggesting environmental factors influence the risk of translocation to the stifle. Organisms detected were predominately Gram's negative Proteobacteria, particularly the orders Rhizobiales (32.8% of clones) and Burkholderiales (20.0% of clones), usually as part of a polymicrobial population. PCR-positivity was inversely correlated with severity of arthritis assessed radiographically and with dog age. Bacterial translocation to the canine stifle may be associated with changes to the indoor environment.
    Veterinary Microbiology 08/2009; 141(1-2):127-33. · 3.13 Impact Factor
  • Trent A Tuttle, Paul A Manley
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine the incidence of, and risk factors for, fibular fracture after tibial plateau leveling osteotomy (TPLO) in dogs. Case series. TPLO (n=168) on 142 dogs. Medical records (January 2006-September 2007) and radiographs of all dogs that had TPLO were reviewed. Data retrieved were breed, sex, age, weight, type of plate, use of a jig, time to recheck, preoperative tibial plateau angle (TPA), immediate postoperative TPA, and presence or absence of fibular fracture. Fibular fractures occurred in 5.4% TPLOs. Body weight, change in TPA, and preoperative TPA were significantly higher in dogs with fibular fracture. TPLO without use of a jig was significantly associated with fibular fracture. Age, postoperative TPA, and plate type were not significantly associated with fibular fracture. Fibular fracture is uncommon after TPLO. Risk factors are increased body weight, greater preoperative TPA, greater change in TPA, and TPLO performed without a jig. All fractures occurred during convalescence. Owners should be warned of potential complications and risk factors associated for fibular fracture after TPLO.
    Veterinary Surgery 05/2009; 38(3):355-60. · 1.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dysregulation of immune responses within joints plays an important role in development of inflammatory arthritis. We determined expression of a panel of immune response and matrix turnover genes in synovial fluid collected from a group of dogs with stifle oligoarthritis and associated degenerative cranial cruciate ligament (CCL) rupture (n=27). We also studied synovial fluid gene expression in dogs affected with other forms of degenerative arthritis (n=9) and in the stifle joint of healthy dogs with intact CCL (n=14). After collection, synovial cells were pelleted and RNA was isolated. Relative expression of cathepsin K, cathepsin S, tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), invariant chain (li), toll-like receptor-2 (TLR-2), and TLR-9 was determined using real-time quantitative RT-PCR. Data were normalized to peripheral blood mononuclear cells (PBMC) as an internal control. Relative expression of cathepsin K, MMP-9, TRAP, and li was increased in the stifle synovial fluid of dogs with oligoarthritis, when compared with the stifles of healthy dogs (P<0.05). In contrast, relative expression of all of the genes-of-interest in synovial fluid from joints affected with other forms of arthritis was not significantly different from the stifles of healthy dogs. TRAP expression was also significantly increased in the stifle joints of dogs with oligoarthritis, when compared to joint expression of TRAP in dogs with other forms of degenerative arthritis (P<0.05). In the dogs with stifle oligoarthritis, expression of both matrix turnover and immune response genes was increased in stifle synovial fluid, when compared with the internal PBMC control, whereas in healthy dogs and dogs with other forms of arthritis, only expression of matrix turnover genes was increased in synovial fluid, when compared with the internal PBMC control (P<0.05). Taken together, these findings suggest that antigen-specific immune responses within the stifle joint may be involved in the pathogenesis of persistent synovitis and associated joint degradation in dogs with oligoarthritis and degenerative CCL rupture.
    Veterinary Immunology and Immunopathology 11/2007; 119(3-4):214-21. · 1.88 Impact Factor
  • Peter Muir, Paul A Manley, Zhengling Hao
    [Show abstract] [Hide abstract]
    ABSTRACT: Inhibition of collagen fragment generation in canine cranial cruciate ligament (CCL) explant cultures by the matrix metalloprotease inhibitor (6-demethyl)-6-deoxy-4-dedimethylamino tetracycline (COL-3) was studied. Cranial cruciate ligament specimens were collected from dogs with inflammatory stifle arthritis/CCL rupture and dogs with normal stifles. Explant cultures from each CCL specimen included one COL-3 treated explant and a baseline control; explants from 12 ruptured CCLs were prepared in triplicate and a protease inhibitor cocktail positive control was used. Explant supernatants were analyzed for generation of collagen fragments after two days. Treatment of ruptured CCL explants with 10(-4)M COL-3 decreased generation of collagen fragments. The extent of this inhibition was increased in explants treated with a protease inhibitor cocktail. Generation of collagen fragments was increased in ruptured CCLs, when compared with intact CCLs. It is concluded that generation of collagen fragments was increased in pathological ruptured CCL explants. This degradation could be significantly inhibited in vitro by 10(-4)M COL-3.
    The Veterinary Journal 10/2007; 174(2):403-6. · 2.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To describe outcome in dogs with insufficient bone healing treated with recombinant human bone morphogenetic protein-2 (rhBMP-2). Retrospective study. Four dogs clinically affected with delayed union or nonunion bone healing. Medical records were reviewed for signalment, clinical problem, treatment, and outcome. Four dogs that had delayed- or nonunion of bone fracture, osteotomy, or arthrodesis were treated with either minimally invasive, fluoroscopically guided, percutaneous administration or direct surgical application of rhBMP-2. Doses used ranged from 0.2 to 1.6 mg of rhBMP-2. In 3 dogs, a calcium phosphate matrix (CPM) carrier was used whereas in 1 dog commercially prepared rhBMP-2 impregnated in an absorbable collagen sponge (INFUSE Bone Graft) was used. This latter dog had osteomyelitis associated with implant infection before rhBMP-2 administration. Rapid radiographic union was noted in all dogs with excellent long-term outcome. Adverse effects were minimal and included transient worsening of lameness after percutaneous administration of rhBMP-2 in 2 dogs. rhBMP-2 stimulated rapid bone formation at delayed- or nonunion sites resulting in radiographic bone union with minimal adverse effects and excellent long-term outcome in 4 dogs. Direct intraoperative administration or fluoroscopically guided, minimally invasive delivery of rhBMP-2 may be an effective treatment modality for bone delayed- or nonunions and could potentially be used to stimulate new bone production in a variety of orthopedic surgical conditions in dogs.
    Veterinary Surgery 03/2007; 36(2):132-40. · 1.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this 18 month in vivo canine study we compared three methods of attaching the gluteal muscles to the proximal femur during hip reconstruction with an allograft-prosthesis composite (APC). All three methods are commonly practiced in human hip revision surgery and data on their effectiveness in dogs is directly relevant to human treatment. The methods compared were host gluteal tendon sutured to allograft tendon, host greater trochanter apposed to allograft using a cable grip system, and host cortical bone shells around the allograft secured with cerclage wires. For each method, we assessed changes in allograft-host bone fusion, weight bearing, gluteal muscle mass, and structural properties through qualitative radiography, gait analysis, histology, and biomechanical testing. Hip reconstruction using the WRAP method resulted in the greatest limb use with complete resolution of gluteal muscle atrophy 18 months after surgery. This method yielded a stronger, more stable hip joint that allowed for more normal limb function. These hips had the more rapid rate of bony union at the host bone-allograft junction and little resorption of the graft. The increased limb use and resultant larger gluteal muscle mass conferred to the WRAP hip composites the greatest tensile strength and stiffness when tested 18 months after reconstruction. There was a large amount of new bone formation on the periosteal surface where the WRAP reconstructions had an overlay of live bone that resulted in a more rapid union and increased cortical width at the level of the osteotomy. New bone also penetrated into the allograft a greater distance from the osteotomy in the WRAP group.
    Journal of Orthopaedic Research 03/2007; 25(2):208-20. · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To compare long-term outcomes of juvenile pubic symphysiodesis (JPS) and triple pelvic osteotomy (TPO) in dogs with hip dysplasia. Prospective clinical trial. 18 dogs with hip dysplasia (ie, distraction index > or = 0.5 in at least 1 hip joint and no, mild, or moderate radiographic evidence of degenerative joint disease [DJD]). Dogs between 4 and 5.5 months old at enrollment were assigned to undergo JPS, and dogs between 5 and 12 months old were assigned to undergo TPO. All dogs were reexamined at 2 years of age. At 2 years of age, there were no significant differences between groups in regard to lameness scores, angle of extension of the hip joints, distraction index, peak vertical force, acetabular angle, radiographic DJD score, or owner-assigned scores of clinical function. Dorsal acetabular rim angle was significantly higher in dogs that underwent JPS than in dogs that underwent TPO. For dogs that underwent TPO, dorsal acetabular rim angle was significantly decreased and acetabular angle was significantly increased at 2 years of age, compared with values obtained prior to surgery. Results suggest that JPS and TPO have similar effects on hip joint conformation in dogs with moderate to severe hip dysplasia but that neither procedure eliminates the hip joint laxity characteristic of hip dysplasia or the progression of degenerative changes.
    Journal of the American Veterinary Medical Association 02/2007; 230(2):206-10. · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mixtures of bacterial nucleic acids can often be detected in synovial joints affected with arthritis. We investigated the potential role of such mixtures of bacterial nucleic acids in the pathogenesis of arthritis in a naturally occurring canine model. Dogs with a common inflammatory knee arthritis in which associated pathological degenerative anterior cruciate ligament (ACL) rupture often develops were studied. Synovial biopsies were obtained from 43 dogs with the naturally occurring ACL rupture arthropathy, 12 dogs with normal knees and intact ACL, and 16 dogs with normal knees and experimentally induced ACL rupture. Using PCR, specimens were tested for Borrelia burgdorferi OspA and p66 gene sequences. Broad-ranging 16S rRNA primers were also used; 'panbacterial' PCR products were cloned and multiple clones were sequenced for bacterial identification. Synovium was also studied histologically. The presence of bacterial DNA within the synovium was significantly associated with the naturally occurring ACL rupture arthropathy (p<0.05); knee joints from 37% of these dogs were PCR-positive. Mixtures of bacterial DNA were common and often included environmental bacteria; predominant organisms included Borrelia burgdorferi and Stenotrophomonas maltophilia. DNA from environmental bacteria was only found in dogs with the naturally occurring ACL rupture arthopathy; joints from 33% of affected dogs contained such bacterial DNA. Synovial inflammation developed in dogs with both naturally occurring and experimentally induced ACL rupture, when compared with intact ACL controls (p<0.01). These results indicate that mixtures of DNA derived from environmental bacteria are commonly found in the knee joint of a naturally occurring canine arthropathy, often in association with a recognized joint pathogen. Our results also suggest that knee instability alone is not responsible for this finding and have led us to hypothesize that mixtures of bacterial DNA are an important causative factor in the pathogenesis of inflammatory arthritis in this canine model.
    Microbial Pathogenesis 01/2007; 42(2-3):47-55. · 1.97 Impact Factor
  • Source
    Brian M Daubs, Mark D Markel, Paul A Manley
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. Femoral heads from clinically normal dogs (n = 16) and dogs with moderate (24) or severe (14) osteoarthritis. 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. 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. 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.
    American Journal of Veterinary Research 11/2006; 67(10):1719-24. · 1.35 Impact Factor
  • Peter Muir, Paul A Manley, Zhengling Hao
    [Show abstract] [Hide abstract]
    ABSTRACT: Collagen fragmentation in cranial cruciate ligament (CCL) explants and stifle synovial fluid was investigated in dogs with ruptured and intact CCL. Cathepsin K and tartrate-resistant acid phosphatase (TRAP) activities were determined in CCL explant supernatants. Formation of collagen fragments was determined in explant supernatants and stifle synovial fluid. Cathepsin K(+) and TRAP(+) cells were stained specifically in histological sections of CCL. Formation of telopeptide collagen fragments was increased in ruptured CCL explants and stifle synovial fluid from dogs with ruptured CCL. In ruptured CCL explants, release of collagen fragments was associated with extracellular release of TRAP and the presence of cathepsin K(+) cells within CCL tissue. Cathepsin K(+) and TRAP(+) cells were only seen in ruptured CCL. It was concluded that infiltration of the CCL with TRAP(+) cells in dogs with CCL rupture is associated with increased collagenolysis. It is hypothesized that recruitment and activation of TRAP(+) mononuclear cells within the synovium and CCL precipitates CCL rupture through upregulation of collagenolytic enzymes and collagen degradation.
    The Veterinary Journal 08/2006; 172(1):121-8. · 2.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chondromalacia can cause joint pain and synovial effusion with the potential for developing into osteoarthritis. Thermal chondroplasty using radiofrequency energy (RFE) has been reported to be superior to mechanical debridement for treating chondromalacia. We compared short-term changes in biomechanical properties of articular cartilage after treatment with monopolar (mRFE) or bipolar RFE (bRFE) or mechanical debridement (MD) on experimentally created grade II chondromalacia patellae. Chondromalacia patellae was created arthroscopically in both patellae of 15 ponies. Ten months after surgery, each patella was randomly assigned to one of four experimental groups: sham operated, untreated control; MD; bRFE; and mRFE. Animals were euthanized 6 months after treatment and fresh osteochondral sections were collected from the treated area, the border of the chondromalacic and nonchondromalacic area, and from two untreated areas for analysis of mechanical properties. The same areas were harvested from an additional six untreated ponies. The aggregate modulus (H(A)), Poisson's ratio (nu(s)), and permeability (k) were determined for each area under creep indentation, and cartilage thickness was measured with a needle probe. The relation between zone of calcified cartilage (ZCC) and mechanical properties of hyaline cartilage (HC) was assessed histomorphometrically. Treated areas of all four groups had inferior mechanical properties compared at the same location. The treated and border areas had significantly lower H(A) values than the untreated areas. Permeability values showed significant differences between bRFE and other treated groups. Chondromalacic areas showed thinning of cartilage compared to nonchondromalacic areas. Biomechanical properties of the injured cartilage were inferior to nonchondromalacic cartilage regardless of the treatment type. mRFE had the highest stiffness value compared to other treatments and significantly higher values than MD. A significant correlation was observed between the mechanical properties of HC and ZCC thickness.
    Journal of Orthopaedic Research 05/2006; 24(4):716-24. · 2.88 Impact Factor
  • Source
    Journal of Orthopaedic Research 12/2005; 19(5):990 - 990. · 2.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Disruption of the murine Mop3 (also known as Bmal1 or Arntl) locus results in a loss of behavioral and molecular circadian rhythms. Although Mop3 null mice do not display anomalies in early development, they do display reduced activity as they age. In an effort to explain this decreased activity, we characterized the physiological and anatomical changes that occurred with age. We observed that Mop3 null mice display an increased mortality after 26 weeks of age and a phenotype best described as a progressive noninflammatory arthropathy. Although little pathology is observed prior to 11 weeks of age, by 35 weeks of age essentially all Mop3 null animals develop joint ankylosis due to flowing ossification of ligaments and tendons and almost complete immobilization of weight-bearing and nonweight-bearing joints. This pathology appears to explain the decreased activity of Mop3 null mice and suggests that MOP3 is an inhibitor of ligament and tendon ossification.
    genesis 04/2005; 41(3):122-32. · 2.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To describe the histomorphometric properties of epiphyseal and metaphyseal trabecular bone of the proximal portion of the femur of dogs with moderate osteoarthritis. Proximal portions of a femour from 24 dogs. The proximal portion of a femur was obtained from each dog. Eleven and thirteen specimens were sectioned in the transverse and coronal planes, respectively. Three evenly spaced sections from each specimen were chosen, surface stained, and digitized, and the stained areas were preferentially selected. Custom software was used for histomorphometric analysis of each section. A mixed-model analysis was used to evaluate the effect of slice location and region on 6 parameters, and a Fisher protected t test was used when differences were detected. There was a significant difference between the femoral head and femoral neck for all parameters tested. In coronal sections, the femoral neck was significantly more anisotropic than the femoral head. In transverse sections, the craniolateral region of the femoral neck was significantly more anisotropic than the caudomedial and craniomedial regions. There is a predictable cancellous microarchitecture in the proximal portion of femurs from dogs with moderate osteoarthritis. Trabeculae are more numerous, thicker, and closer together but more randomly arranged in the femoral head than in the femoral neck. Dogs with moderate osteoarthritis had an increase in trabecular anisotropy in the craniolateral region of the femoral neck. However, there was no corresponding increase in trabecular alignment of the proximomedial region of the femoral head. Results support an association between trabecular alignment and the progression of osteoarthritis.
    American Journal of Veterinary Research 02/2005; 66(1):150-5. · 1.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To localize cathepsin K and tartrate-resistant acid phosphatase (TRAP) in synovium and cranial cruciate ligament (CCL) of dogs with cruciate disease. Dogs (n=15) with cruciate disease and ruptured CCL, and 12 dogs with intact CCL. Synovium and CCL were examined histologically and cells containing cathepsin K or TRAP were identified immunohistochemically and histochemically, respectively. Increased cellular localization of cathepsin K and TRAP was detected in synovium and ruptured CCL in dogs with cruciate disease, when compared with tissues from dogs with intact CCL. Inflammation of synovium with TRAP+ macrophage-like cells was seen in 73% of dogs with CCL disease, but was not seen in dogs with intact CCL. The presence of cathepsin K and TRAP protein in synovium and CCL tissues was significantly correlated in dogs with CCL rupture. Inflammation of the epiligament of ruptured CCL with cathepsin K+ and TRAP+ macrophage-like cells forms part of a similar, more generalized chronic inflammatory change within the periarticular tissues of the stifle of a large proportion of dogs with CCL rupture. Production of matrix-degrading enzymes by the synovium may induce progressive pathologic rupture of the CCL. Therefore, these collagenolytic pathways may offer a novel target for medical therapy of joint inflammation in canine patients with cruciate disease.
    Veterinary Surgery 01/2005; 34(3):239-46. · 1.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine expression of collagenolytic genes and collagen degradation in stifle tissues of dogs with ruptured cranial cruciate ligament (CCL). Six dogs with CCL rupture and 11 dogs with intact CCL. Gene expression in CCL tissue and synovial fluid cells was studied using reverse transcriptase-polymerase chain reaction (RT-PCR). Collagen degradation was studied using CCL explant cultures and a synovial fluid bioassay. Expression of matrix metalloproteases (MMP) was not found in young Beagles with intact CCL; however, increased expression of MMP-3 was found in CCL tissue from older hounds with intact CCL, when compared with young Beagles. In dogs with ruptured CCL, expression of MMP-2 and -9 was increased in stifle tissues, when compared with dogs with intact CCL. Similar to MMP-9, expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin S was only found in stifle tissues from dogs with ruptured CCL; in contrast, expression of cathepsin K was found in all ruptured and intact CCL. Collagen degradation was increased in ruptured CCL, when compared with intact CCL. Rupture of the CCL is associated with up-regulation of expression of MMP-2 and -9 (gelatinase A and B), TRAP, and cathepsin S, and increased degradation of collagen. These findings suggest that MMP-2, -9, cathepsin S, and TRAP may be important mediators of progressive joint destruction in dogs with CCL rupture. These genes are markers for macrophages and dendritic cells. MMP and cathepsin S pathways may offer novel targets for anti-inflammatory medical therapy aimed at ameliorating joint degradation associated with inflammatory arthritis.
    Veterinary Surgery 01/2005; 34(5):482-90. · 1.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To compare the effects of caudal pole hemi-meniscectomy (CPHM) and complete medial meniscectomy (MM), specifically with respect to development of secondary osteoarthritis, in the stifle joints of clinically normal dogs. 14 large-breed dogs. Unilateral CPHM (7 dogs) or MM (7) was performed, and the left stifle joints served as untreated control joints. Gait was assessed in all dogs before surgery and at 4, 8, 12, and 16 weeks postoperatively. After euthanasia, joints were evaluated grossly; Mankin cartilage scores, subchondral bone density assessment, and articular cartilage proteoglycan extraction and western blot analyses of 3B3(-) and 7D4 epitopes were performed. Weight distribution on control limbs exceeded that of treated limbs at 4 and 16 weeks after surgery in the CPHM group and at 4 and 8 weeks after surgery in the MM group; weight distribution was not significantly different between the 2 groups. After 16 weeks, incomplete meniscal regeneration and cartilage fibrillation on the medial aspect of the tibial plateau and medial femoral condyle were detected in treated joints in both groups. Mankin cartilage scores, subchondral bone density, and immunoexpression of 3B3(-) or 7D4 in articular cartilage in CPHM- or MM-treated joints were similar; 7D4 epitope concentration in synovial fluid was significantly greater in the MM-treated joints than in CPHM-treated joints. Overall severity of secondary osteoarthritis induced by CPHM and MM was similar. Investigation of 7D4 epitope concentration in synovial fluid suggested that CPHM was associated with less disruption of chondrocyte metabolism.
    American Journal of Veterinary Research 09/2004; 65(8):1053-60. · 1.35 Impact Factor

Publication Stats

707 Citations
120.69 Total Impact Points

Institutions

  • 2011
    • CSU Mentor
      Long Beach, California, United States
  • 1991–2011
    • University of Wisconsin, Madison
      • • School of Veterinary Medicine
      • • Department of Surgical Sciences
      • • Department of Medical Sciences
      Madison, MS, United States