D M Visco

University of North Carolina at Chapel Hill, North Carolina, United States

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Publications (31)103.78 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The dog is a common model for study of osteoarthritis (OA). Subjective histologic scoring systems have often served as the reference standard for presence and severity of OA. However, these scoring systems have perceived shortcomings. The system developed for this report attempts to address these shortcomings by providing a standardized methodology for global assessment of the joint, versatility and the potential for relative weighting of pathology, allowing for comparison among time points, studies, and centers, and critical analysis of the system's reliability. The proposed system for assessment of canine tissues appears to provide an effective method for global assessment of articular pathology in OA. The system is versatile, comprehensive, and reliable and appears to have advantages over conventional scoring systems.
    Osteoarthritis and Cartilage 10/2010; 18 Suppl 3:S66-79. · 4.26 Impact Factor
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    ABSTRACT: Objective. To examine the distribution of the 3-B-3(–) and 7-D-4 epitopes in proteoglycans from morphologically normal and osteoarthritic (OA) canine articular cartilage.Methods. Cartilage samples from the femurs of stable and destabilized stifle joints of 9 dogs that had undergone transection of the cranial cruciate ligament were examined by immunohistochemistry.Results. The 3-B-3(–) and 7-D-4 epitopes were expressed in the superficial zone of cartilage from the destabilized femorotibial joints in the early stages of developing OA. The staining patterns with these two antibodies differed, with 3-B-3(–) reactivity confined to the superficial and upper middle zones of the articular cartilage, and 7-D-4 reactivity more prominent in the matrix, extending into the deeper zones and increasing with progression of the lesion. Both epitopes were also expressed in the superficial and upper middle zones of areas peripheral to the lesions and were detectable before the loss of matrix and proteoglycans could be identified by histochemical staining with toluidine blue.Conclusion. In this study, the expression of atypical chondroitin sulfate proteoglycans was demonstrated in osteoarthritic canine cartilage, and the pattern of expression changed as the lesions progressed. The occurrence of 3-B-3(–) and 7-D-4 epitopes appears to be associated with changes in chondrocyte metabolism in the early stages of cartilage degeneration in experimental osteoarthritis.
    Arthritis & Rheumatology 12/2005; 36(12):1718 - 1725. · 7.48 Impact Factor
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    ABSTRACT: We characterized the mean peak vertical forces (MFz) in five groups of dogs which underwent transection of the left anterior cruciate ligament (ACLT) or sham ACLT and ipsilateral dorsal root ganglionectomy or sham-ganglionectomy, and the relationship of these forces to the severity of osteoarthritis (previously reported) 72 weeks after arthrotomy. Group I (N=7) underwent ACLT; Group II (N=8) underwent ACLT followed 52 weeks later by ganglionectomy; Group III (N=7) underwent ganglionectomy followed 2 weeks later by ACLT; Group IV (N=7) underwent sham-ganglionectomy followed 2 weeks later by ACLT; Group V (N=8) underwent ganglionectomy followed 2 weeks later by sham-ACLT. The dogs were evaluated 2, 6, 12, 24, 52 and 72 weeks after arthrotomy. From 6 weeks after arthrotomy until death, the left hindlimb MFz in Group V was significantly greater (P< 0.05) than that in the other four groups. The MFz of all groups which underwent ACLT decreased after arthrotomy. While the MFz of Group III (very severe OA) was about 10-20% greater than that of Groups I, II and IV (mild OA) 6 and 12 weeks after ACLT, and generally about 5-10% greater subsequently, this difference was not statistically significant. The MFz of Group II returned to pre-ganglionectomy levels, rather than to baseline levels, following ganglionectomy. (1) since the ipsilateral limb of dogs with ganglionectomy+sham ACLT bore normal amounts of weight throughout most of the postsurgical period, and its knee did not develop OA, one cannot argue that the knee was protected from OA because the limb was not used; (2) the fact that the MFz of dogs which underwent ACLT+ganglionectomy returned to pre-ganglionectomy levels, rather than baseline, is consistent with the hypothesis that the unstable joint was protected from accelerated breakdown by a central nervous system that was reprogrammed by sensation from the unstable limb; (3) the slightly-but consistently-greater MFz of dogs which underwent ganglionectomy+ ACLT may contribute to the acceleration of OA in this model.
    Osteoarthritis and Cartilage 11/1999; 7(6):567-73. · 4.66 Impact Factor
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    ABSTRACT: Five gelatin phantoms were constructed to study the effect of matrical hydration on magnetic resonance imaging (MRI) signal intensity using a low-field strength imager. Water content of the phantoms ranged from 75 to 95% weight/weight. Signal intensity values of each phantom were measured using five imaging sequences: proton density, T1-weighted, T2-weighted, inversion recovery with short inversion time, and inversion recovery with long inversion time. There was significant positive correlation (p < .05) of signal intensity with differences in hydration using the T2-weighted sequence and the inversion recovery sequence with short inversion time. Significant negative correlations (p < .05) were found with T1-weighted imaging and the inversion recovery sequence with long inversion time. In a second part of the study, in vivo focal variations in MRI signal intensity were evaluated in a canine cranial cruciate ligament deficient model of osteoarthritis. Signal intensity measurements were obtained from multiple areas of articular cartilage to identify an initial stage in osteoarthritis that is characterized in part by increased hydration of articular cartilage. At 6 weeks post-transection of the cranial cruciate ligament, an increase in signal intensity was detected in the articular cartilage of the weight-bearing portion of the lateral femoral condyle and the caudal portion of the medial tibial condyle with T1-weighted imaging. The increase in signal intensity may reflect increased proteoglycan synthesis by chondrocytes that also occurs early in the pathogenesis of osteoarthritis.
    Veterinary Radiology &amp Ultrasound 01/1999; 40(1):27-35. · 1.26 Impact Factor
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    ABSTRACT: Investigation of furans, pyrroles and pyrazolones identified 3-pyridyl-2,5-diaryl-pyrroles as potent, orally bioavailable inhibitors of p38 kinase. 3-(4-pyridyl-2-(4-fluoro-phenyl)-5-(4-methylsulfinylphenyl)-pyrrol e (L-167307) reduces secondary paw swelling in the rat adjuvant arthritis model: ID50 = 7.4 mg/kg/b.i.d.
    Bioorganic & Medicinal Chemistry Letters 11/1998; 8(19):2689-94. · 2.33 Impact Factor
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    ABSTRACT: Six healthy adult male mongrel dogs underwent cranial cruciate ligament transection in the left stifle. Survey radiography of both stifles and low-field (0.064 T) MRI of the left stifle were performed preoperatively and at 2, 6, and 12 weeks postoperatively. Focal changes in signal intensity were seen with MRI in the subchondral bone of the medial tibial condyle at 2 and 6 weeks postoperatively. At 12 weeks postoperative, a cyst-like lesion was detected using MRI in the subchondral bone of the medial tibial condyle in 4 of 6 dogs and a less defined lesion at this site in the remaining 2 dogs. The cyst-like lesion was spherical in shape and showed typical characteristics of fluid with low signal intensity on T1-weighted images, high signal intensity on T2-weighted images and high signal intensity on inversion recovery images. The lesion was seen in the subchondral bone of the caudal medial and/or middle region of the tibial plateau slightly cranial to the insertion of the caudal cruciate ligament. No subchondral cysts were seen in the tibia on radiographs. Histopathologically, the tibia was characterized by a loose myxomatous phase of early subchondral cyst formation.
    Veterinary Radiology &amp Ultrasound 04/1998; 39(3):167 - 173. · 1.41 Impact Factor
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    ABSTRACT: Low-field magnetic resonance imaging (MRI) was performed on the stifle joints of four normal adult mongrel dogs using a 0.064 Tesla scanner. Markers were placed on each stifle joint to serve as reference points for comparing gross sections with the images. A T1-weighted sequence was used to image one stifle joint on each dog in the sagittal plane and the other stifle joint in the dorsal plane. The dogs were euthanized immediately following MRI and the stifle joints frozen intact. Each stifle joint was then embedded in paraffin, again frozen, and sectioned using the markers as reference points. On T1-weighted images, synovial fluid had low signal intensity (dark) compared to the infrapatellar fat pad which had a high signal intensity (bright). Articular cartilage was visualized as an intermediate bright signal and was separated from trabecular bone by a dark line representing subchondral bone. Menisci, fibrous joint capsule, and ligamentous structures appeared dark. In the true sagittal plane, the entire caudal cruciate ligament was often seen within one image slice. The patella was visualized as an intermediate bright signal (trabecular bone) surrounded by a low intensity signal (cortical bone). The trochlea and the intercondylar notch were difficult areas to analyze due to signal volume averaging of the curved surface of these areas and the presence of several types of tissues.
    Veterinary Radiology &amp Ultrasound 03/1998; 39(2):87-97. · 1.26 Impact Factor
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    ABSTRACT: Up-regulation of the inducible isoform of nitric oxide synthase (iNOS) was determined during the development of adjuvant-induced arthritis in the rat. iNOS enzymatic activity, measured in spleen tissue, appeared and increased coincidentally with the appearance and degree of paw swelling and joint destruction in this arthritis model, when measured on days 0 through 21 subsequent to inoculation of the rats with adjuvant. The increase in enzymatic activity was paralleled by an increase in the plasma nitrite/nitrate (NOx) level and the appearance of immunoreactive iNOS, as measured by Western immunoblot, in the spleens of these rats. Prophylactic administration of N-iminoethyl-L-lysine (L-NIL) completely abolished iNOS activity (plasma NOx elevation) and effectively reduced both the swelling and radiographic changes in the joint tissues of the noninjected paw measured on day 21. However, therapeutic administration of L-NIL beginning on day 14 had no effect on the inflammatory or arthritic changes measured on day 21, even though plasma NOx levels were reduced to that of the naive controls. These results suggest that iNOS may be involved with the initial stages of the immune response to adjuvant injection, but its product, NO, does not mediate the chronic inflammation and joint destruction which occur during the later phase in this model.
    Journal of Pharmacology and Experimental Therapeutics 03/1998; 284(2):714-21. · 3.86 Impact Factor
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    ABSTRACT: The gross morphology of the musculus articularis genus and the location of muscle spindles at its point of insertion were studied in 18 adult dogs. The m. articularis genus was usually small and bipartite. From its originate on the cranial surface of the distal femur, it passed distally to terminate at the femoropatellar-joint capsule surface and extend into the synovial membrane. Although the m. articularis genus was usually composed of two parts, only a medial part was present in some dogs and was entirely absent in one specimen. Innervation to the m. articularis genus was provided by a branch of the femoral nerve. Muscle spindles were abundant in the termination of the muscle. spindles were abundant in the termination of the muscle. Frequently, the spindles were not in contact with muscle fibers (dissociated). Muscle spindles were located in close proximity to the surface of the synovial membrane. Morphological adaptations of the m. articularis genus support its potential function as a monitor of joint movement rather than an extensor of the stifle joint.
    Anantomia Histologia Embryologia 07/1996; 25(2):113-6. · 0.74 Impact Factor
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    ABSTRACT: Lesions induced by transecting the cranial cruciate ligament in two surgical models of osteoarthritis (OA) in mature, male, cross-bred dogs were compared by using an established grading system and alternatives. Previously, we relied on evaluations of lesions in articular cartilage on femurs alone. No statistically significant differences were found between grades for lesions in cartilage when either treated or control joints were compared by surgical method. Because the Pond-Nuki method yielded statistically significant differences between grades for lesions affecting treated and control femurs or tibias, and for some parameters indicative of synovitis, we preferred this method of surgery. Although by using the medial arthrotomy method of surgery, we were able to destabilize the joint in a more consistent manner, significant differences between treated and control joints were found for lesions on tibias, but not femurs, a frequent site for OA in humans. Suggestions are made for enhancing the surgical models and for a more holistic approach to evaluating joints morphologically.
    Osteoarthritis and Cartilage 04/1996; 4(1):9-22. · 4.66 Impact Factor
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    ABSTRACT: The presence and distribution of tumor necrosis factor-alpha (TNF-alpha), TNF receptors and stromelysin [matrix metalloproteinase 3 (MMP-3)] in articular cartilage were evaluated in an iatrogenically induced model of osteoarthritis (OA). Eleven adult male dogs were assigned randomly to a control group (N = 4) or an OA group (N = 7). Osteoarthritis was created by surgical transection of the cranial cruciate ligament of one stifle joint. Both femoral condyles were sampled 3 months post-surgery at necropsy and immunohistochemically analyzed for the presence of the aforementioned cytokines and receptors. Chondrocytes stained for TNF-alpha and TNF receptors in control articular cartilage, spanning an area encompassing most of the middle and deep zones. Positive matrical and chondrocytic staining for TNF-alpha, TNF receptors, and stromelysin was present in OA articular cartilage. Staining varied in intensity and distribution and was dependent of the severity of the lesion. Smooth muscle cells of arteries and arterioles (periarticular synovial membrane) were stained for only one (p55) of two TNF receptors; this staining was confined to control tissues. Results indicate that the differential expression of TNF-alpha and its receptors may be important in the normal maintenance of articular cartilage. The increased presence of TNF-alpha and its receptors in articular cartilage with mild osteoarthritic changes suggests a role in the development of early OA. Regulating TNF-alpha may be an important component in the treatment of OA.
    Osteoarthritis and Cartilage 04/1996; 4(1):23-34. · 4.66 Impact Factor
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    ABSTRACT: When lameness occurs in a load-bearing limb, compensatory load adjustments are made in the other supporting limbs. The vertical component of the ground reaction force, as measured by force platform analysis, reflects these adjustments. This study describes the pattern of vertical ground reaction force redistribution during experimental, chronic hindlimb lameness in dogs. The peak and impulse of the vertical ground reaction force were measured and described in 13 dogs before, and at 2, 6, and 12 weeks after transection of the cranial cruciate ligament. These variables were compared among limbs. The vertical ground reaction force in the forelimbs did not change significantly during the course of the study. At 2, 6, and 12 weeks after surgery, means of peak vertical force in the limb that underwent surgery were 18.9%, 44.0%, and 61.3% respectively, of presurgical values. In the contralateral limb, corresponding values were 131.7%, 112.8% and 112.9% respectively. If one accepts the relationship of mechanical loading to musculoskeletal architecture and the now certain relationship between lameness and compensatory loading of other limbs, then the use of another limb of the same animal as a control is a potential study design flaw.
    Veterinary Surgery 09/1995; 24(5):384-9. · 0.99 Impact Factor
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    ABSTRACT: Objective. To evaluate the potential of using monoclonal antibodies (MAb) 3-B-3(–) and 7-D-4 to detect biochemical markers of altered cartilage metabolism in human arthritides.Methods. Fifty-five samples of normal articular cartilage (subjects' age range 18 weeks of gestation to 83 years of age) and 89 samples of arthritic cartilage (patients' age range 20–81 years) were collected, and their proteoglycans were extracted and analyzed for the presence of the epitopes recognized by MAb 3-B-3 and 7-D-4.Results. Native 3-B-3(–) mimotope was expressed at a high incidence in proteoglycans extracted from the cartilage of patients with most of the arthritic diseases examined (osteoarthritis, juvenile rheumatoid arthritis, rheumatoid arthritis, avascular necrosis, and degenerative meniscal tears). Its expression in normal cartilage specimens was very low or absent, occurring mainly in the young, skeletally immature individuals. In contrast, expression of the 7-D-4 epitope was more variable in patients with different arthritides and was also frequently found in normal cartilage specimens. Immunohistochemical analyses with both 3-B-3(–) and 7-D-4 showed strong focal positive staining in superficial areas, where cartilage degeneration, remodeling, and repair were greatest.Conclusion. The biochemical markers recognized by MAb 3-B-3(–) and 7-D-4 are indicative of altered proteoglycan synthesis and metabolism in human articular cartilage. The data suggest that in human cartilage, the 3-B-3(–) epitope might be a better marker of biochemical changes than the 7-D-4 epitope.
    Arthritis & Rheumatology 04/1995; 38(5):655 - 659. · 7.48 Impact Factor
  • International Archives of Allergy and Immunology 01/1995; 107(1-3):333-5. · 2.43 Impact Factor
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    ABSTRACT: Radiography and magnetic resonance imaging were used to evaluate osteoarthritis at 2, 6, and 12 weeks following transection of the cranial cruciate ligament of the stifle (femorotibial) joint of 6 dogs. A quantitative radiographic scoring system was used to assess the progression of hard and soft tissue changes of osteoarthritis. Mediolateral (flexed joint) and oblique (extended joint) radiographic projections enabled identification of small osteophytes on the femoral trochlear ridges, which were detected at an earlier stage of development than was previously reported. Magnetic resonance imaging was useful in detecting changes in cartilage thickness, osteophytosis and intraarticular loose bodies. Radiography and magnetic resonance imaging were complementary in the assessment of pathologic changes of osteoarthritis.
    Veterinary Radiology &amp Ultrasound 08/1994; 35(5):371 - 384. · 1.41 Impact Factor
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    ABSTRACT: Force platform analysis of gait provides ground reaction force information that can be used to study limbs with normal or abnormal function. When combined, the interrelated variables of ground reaction forces give a more thorough description of gait than when used individually. To describe the pattern of ground reaction forces in clinically normal, conditioned, mesomorphic dogs, we studied the data from platform gait analyses of 43 dogs. Mediolateral (Fx), craniocaudal (Fy), and vertical (Fz) forces were measured and recorded. Torque (Tz) around the vertical axis also was calculated. Mean stance times for forelimbs and hind limbs were 0.278 and 0.261 second, respectively. Among dogs, ground reaction forces were normalized and expressed as percentage of body weight (%bw). The vertical (Fz) peak, average force during stance phase, and force vs time impulses were 106.68, 60.82, and 17.2 %bw in forelimbs, and were 65.11, 35.3, and 9.33 %bw in hind limbs. The forelimb braking/propulsive (Fy) peaks were -16.74 and +6.73 %bw. In hind limbs, these peaks were -3.76 and +7.69 %bw. The usual mediolateral force (Fx) pattern found in forelimbs was laterally directed, with average peak magnitude of 6.69 %bw, whereas the hind limb patterns were variable.
    American Journal of Veterinary Research 07/1994; 55(6):756-61. · 1.21 Impact Factor
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    ABSTRACT: The slow rate at which articular cartilage degrades in dogs after transection of the anterior cruciate ligament (ACLT) has been attributed to capsular thickening and buttressing by osteophytes. We investigated the roles of the peripheral and central nervous systems in protecting knee joints with chronic ACL deficiency from breakdown. Five groups of dogs were studied; all were killed 72 weeks after left knee surgery. Group A had ACLT, group B had ACLT followed 52 weeks later by ipsilateral L4-S1 dorsal root ganglionectomy (DRG), group C had DRG followed 2 weeks later by ACLT, group D had sham DRG followed 2 weeks later by ACLT, and group E had DRG followed 2 weeks later by sham ACTL. Group E dogs did not develop knee pathology. All cruciate-deficient knees were lax at the end of the study. The osteoarthritis (OA) that developed in groups A, B, and D was comparable (P > 0.05), and was significantly greater than that in group E (P < 0.05). Group C developed much more severe OA than any of the other groups (P < 0.05). Ipsilateral sensory input is temporarily important in protecting the unstable joint from rapid breakdown. Over time, the central nervous system apparently acquires the ability to protect the unstable joint without continued ipsilateral sensory input.
    Arthritis & Rheumatology 08/1993; 36(8):1154-63. · 7.87 Impact Factor
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    ABSTRACT: The pattern of vertical ground reaction force redistribution among limbs during episodes of acute synovitis of the stifle in 12 mixed-breed dogs was investigated as an adjunct to a blinded nonsteroidal anti-inflammatory drug efficacy study. Without regard to drug efficacy groupings, the redistribution of vertical forces before and during the acute synovitis episode was evaluated by analysis of gait, using a force platform. Acute synovitis was induced by intrasynovial injection of sodium urate crystals. Simultaneously, each dog was given 1 of 4 treatment regimens, including IV injection of sterile saline solution (as a negative control), phenylbutazone (as a positive control), or 1 of 2 proprietary nonsteroidal anti-inflammatory drugs. Postinjection analyses took place at 2, 4, 8, 12, 24, and 36 hours. The peak vertical force redistribution in the 3 untreated limbs of the dogs was described. The greatest redistribution was observed 4 hours after substance injection when the synovitis was clinically at maximum. Thereafter, there was steady improvement and the dogs had a clinically normal gait 24 hours after substance injection. During synovitis, peak vertical force increased in the contralateral hind limb. During the more severe synovitis episodes, force was decreased in both forelimbs. There was good correlation between severity of lameness and peak vertical force response in the contralateral hind limb. Results of the study indicate that the untreated limbs of the same animal should not be used as a control during acute lameness studies.
    American Journal of Veterinary Research 04/1993; 54(3):365-9. · 1.21 Impact Factor
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    ABSTRACT: The development of osteoarthrosis in unstable knee joints of dogs after transection of the anterior cruciate ligament is greatly accelerated when the afferent nerve fibers from the ipsilateral hindlimb have been interrupted by dorsal root ganglionectomy before transection. The purpose of the current study was to determine whether partial loss of the afferent fibers from the knee joints of dogs, accomplished by neurectomy of the primary articular nerves before transection of the ligament, also accelerates the development of osteoarthrosis. Osteoarthrosis did not develop in dogs that had had transection of the medial, posterior, and lateral articular nerves to the left knee joint but had an intact anterior cruciate ligament. Osteoarthrosis developed in all dogs that had had transection of the anterior cruciate ligament. However, the osteoarthrotic lesions, as gauged by histological and macroscopic criteria, were more frequent and severe in dogs that had had neurectomy before transection than in those that had intact sensory nerves and an unstable joint (p less than or equal to 0.05). A subchondral fracture occurred in three dogs that had had neurectomy and had an unstable joint but in none of the dogs that had intact sensory nerves and an unstable joint.
    The Journal of Bone and Joint Surgery 04/1992; 74(3):367-76. · 4.31 Impact Factor
  • Journal of the American Veterinary Medical Association 07/1991; 198(11):1914-22. · 1.67 Impact Factor

Publication Stats

871 Citations
103.78 Total Impact Points


  • 2005
    • University of North Carolina at Chapel Hill
      North Carolina, United States
  • 1998–1999
    • West Haven University
      West Haven, Connecticut, United States
  • 1994–1998
    • Auburn University
      • College of Veterinary Medicine
      Auburn, Alabama, United States
  • 1987–1991
    • Purdue University
      • Department of Veterinary Clinical Sciences (VCS)
      West Lafayette, IN, United States
  • 1989
    • Indiana University-Purdue University Indianapolis
      • Department of Orthopaedic Surgery
      Indianapolis, Indiana, United States