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Publication History View all

  • Bone 09/2013; 57(2). DOI:10.1016/j.bone.2013.09.011
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    ABSTRACT: Osteoarthritis (OA) is the most common joint disease characterised by degradation of articular cartilage and bone remodelling. For almost a decade chondrocyte apoptosis has been investigated as a possible mechanism of cartilage damage in OA, but its precise role in initiation and/or progression of OA remains to the determined. The aim of this study is to determine the role of chondrocyte apoptosis in spontaneous animal models of OA. Right tibias from six male Dunkin Hartley (DH) and Bristol Strain 2 (BS2) guinea pigs were collected at 10, 16, 24 and 30 weeks of age. Fresh-frozen sections of tibial epiphysis were microscopically scored for OA, and immunostained with caspase-3 and TUNEL for apoptotic chondrocytes. The DH strain had more pronounced cartilage damage than BS2, especially at 30 weeks. At this time point, the apoptotic chondrocytes were largely confined to the deep zone of articular cartilage (AC) with a greater percentage in the medial side of DH than BS2 (DH: 5.7%, 95% CI: 4.2-7.2), BS2: 4.8%, 95% CI: 3.8-5.8), p > 0.05). DH had a significant progression of chondrocyte death between 24 to 30 weeks during which time significant changes were observed in AC fibrillation, proteoglycan depletion and overall microscopic OA score. A strong correlation (p ≤ 0.01) was found between chondrocyte apoptosis and AC fibrillation (r = 0.3), cellularity (r = 0.4) and overall microscopic OA scores (r = 0.4). Overall, the rate of progression in OA and apoptosis over the study period was greater in the DH (versus BS2) and the medial AC (versus lateral). Chondrocyte apoptosis was higher at the later stage of OA development when the cartilage matrix was hypocellular and highly fibrillated, suggesting that chondrocyte apoptosis is a late event in OA.
    International Journal of Molecular Sciences 09/2013; 14(9):17729-17743. DOI:10.3390/ijms140917729
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    ABSTRACT: The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus. Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells. In conclusion, it should not be assumed that degenerative changes always precede disc herniation. Cite this article: Bone Joint J 2013;95-B:1127-33.
    The Bone & Joint Journal 07/2013; 95-B(8):1127-1133. DOI:10.1302/0301-620X.95B8.31660
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    ABSTRACT: In order to apply hinged transarticular external skeletal fixation for stabilization of the injured canine tarsal joint, knowledge of the three-dimensional (3D) location and orientation of the transverse axisis necessary. This method of immobilization may be used as a primary or adjunctive method of stabilisation for a large number of traumatic conditions. Using pin-mounted markers in the cadaveric Greyhound crus and talus, a closed-form solution of absolute orientation was used to identify, on radiographs, the lateral and medial locations of the transverse axis by tracking the 3D excursions of the markers during flexion and extension. A line was drawn across the dorsal aspect of the calcaneus from the most dorsal point on the distal articular surface (proximal intertarsal joint: PIJ) to the most dorsal point on its proximal articulation with the body of the talus, and the location of the centre of rotation was expressed in terms of the length of that line. In seven Greyhound tarsal joints, the medial end of the axis was located 73 ± 10% proximal to the PIJ and 11 ± 7% dorsal to the line. The lateral end was 73 ± 9% proximal to the PIJ and -2 ± 3% plantar to the line.
    Veterinary and Comparative Orthopaedics and Traumatology 04/2013; 26(4). DOI:10.3415/VCOT-12-11-0147
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    ABSTRACT: OBJECTIVE: To devise a kinematic technique to objectively ascertain the location and orientation of the centre of rotation of the canine elbow and to compare this axis following arthroplasty with the first generation TATE™ prosthesis in an ex vivo model. METHODS: Five pairs of cadaveric forelimbs were obtained and proximal limb soft tissues removed. Pin-mounted reflective markers were applied to the humerus and ulna. Limbs were mounted on a frame and six trials of the elbow manually cycled through its sagittal range of motion captured using 4 Qualisys cameras at 120 Hz. Radiography was performed to identify marker position. TATE™ cartridges were implanted and kinematic analysis repeated. Kinematic data were imported into custom software and the three-dimensional joint centre of rotation defined using a closed-form solution for absolute orientation. Paired t tests were performed to determine if the centre of rotation of the elbow differed significantly (P<0·05) pre- and postoperatively and between left and right limbs. RESULTS: There was no significant difference in three-dimensional orientation of the elbow axis between pre and postoperative measurements or between left and right limbs. CLINICAL SIGNIFICANCE: A critical factor in obtaining a successful functional outcome following elbow arthroplasty in humans is accurate reconstruction of the anatomic centre of rotation. The first generation TATE canine elbow arthroplasty cartridge and its instrumentation accurately reconstructed the anatomic centre of rotation in 8 of the 10 elbows assessed in this ex vivo model.
    Journal of Small Animal Practice 04/2013; DOI:10.1111/jsap.12060
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    ABSTRACT: We review the evidence that there are two types of disc degeneration. 'Endplate-driven' disc degeneration involves endplate defects and inwards collapse of the annulus, has a high heritability, mostly affects discs in the upper lumbar and thoracic spine, often starts to develop before age 30 years, usually leads to moderate back pain, and is associated with compressive injuries such as a fall on the buttocks. 'Annulus-driven' disc degeneration involves a radial fissure and/or a disc prolapse, has a low heritability, mostly affects discs in the lower lumbar spine, develops progressively after age 30 years, usually leads to severe back pain and sciatica, and is associated with repetitive bending and lifting. The structural defects which initiate the two processes both act to decompress the disc nucleus, making it less likely that the other defect could occur subsequently, and in this sense the two disc degeneration phenotypes can be viewed as distinct.
    Journal of Anatomy 08/2012; 221(6):497-506. DOI:10.1111/j.1469-7580.2012.01551.x
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    ABSTRACT: Central nociceptin/orphanin FQ (N/OFQ)- expressing neurones are abundantly expressed in the hypothalamus and limbic system and are implicated in the regulation of activity of hypothalamo-pituitary-adrenal axis (HPA) activity and stress responses. We investigated the role of the endogenous N/OFQ receptor (NOP) system using the non-peptidic NOP antagonist, JTC-801, during the HPA axis response to acute physical/ psychological stress (60 min restraint). Although i.v. JTC-801 (0.05 mg ⁄kg in 100 μl) had no significant effect on restraint-induced plasma corticosterone release at 30 or 60 min post-injection, i.v. JTC-801 (0.05 mg ⁄kg in 100 μl) in quiescent rats significantly increased basal plasma corticosterone at the 30-min time-point compared to i.v. vehicle (1% DMSO in sterile saline). Central injection of JTC-801 i.c.v. was associated with increased Fos expression in the parvocellular paraventricular nucleus (PVN) 90 min after infusion compared with vehicle control. These findings contrast to the effects of i.c.v. UFP-101, a NOP antagonist that we have previously shown to have no effect on HPA activity in quiescent rats. To determine whether restraint stress was associated with compensatory changes in N ⁄ OFQ precursor (ppN/OFQ) or NOP receptor mRNAs, in a separate study we undertook RT-PCR and in situ hybridisation analysis of ppN/OFQ and NOP transcripts in brains of male Sprague-Dawley rats. In support of an endogenous role for central N ⁄ OFQ in psychological stress, we found that acute restraint significantly decreased preproN ⁄ OFQ transcript expression in the hippocampus 2 h after stress compared to unstressed controls. PpN/OFQ mRNA was also reduced in the mediodorsal forebrain 4h after stress. NOP mRNA was reduced in the hypothalamus 2 h after restraint and at 4h in mediodorsal forebrain and hippocampus. In situ hybridisation analysis showed that acute restraint significantly decreased ppNN/OFQ in the central amygdala with significantly increased expression in bed nucleus and reticular thalamus associated with repeated restraint. There was a strong trend for reduced NOP mRNA in the bed nucleus of acute and repeated restraint groups although there were no other significant changes seen. Although the exact mechanisms require elucidation, the findings obtained in the present study provide evidence indicating that the endogenous N/OFQ system is involved in both acute and chronic restraint stress responses. In summary, our findings confirm the significant role of endogenous NOP receptors and tonic N/OFQ function in the response to the psychological stress of restraint © 2012 The Authors. Journal of Neuroendocrinology © 2012 Blackwell Publishing Ltd.
    Journal of Neuroendocrinology 07/2012; 24(12). DOI:10.1111/j.1365-2826.2012.02361.x
  • Equine Veterinary Journal 07/2012; 44(4):377-8. DOI:10.1111/j.2042-3306.2012.00589.x
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    ABSTRACT: STUDY DESIGN.: Mechanical and biochemical analyses of cadaveric and surgically removed discs. OBJECTIVE.: To test the hypothesis that fissures in the annulus of degenerated human discs are mechanically and chemically conducive to the ingrowth of nerves and blood vessels. SUMMARY OF BACKGROUND DATA.: Discogenic back pain is closely associated with fissures in the annulus fibrosus, and with the ingrowth of nerves and blood vessels. METHODS.: Three complementary studies were performed. First, 15 cadaveric discs that contained a major annulus fissure were subjected to 1 kN compression, while a miniature pressure transducer was pulled through the disc to obtain distributions of matrix compressive stress perpendicular to the fissure axis. Second, Safranin O staining was used to evaluate focal loss of proteoglycans from within annulus fissures in 25 surgically removed disc samples. Third, in 21 cadaveric discs, proteoglycans (sulfated glycosaminoglycans [sGAGs]) and water concentration were measured biochemically in disrupted regions of annulus containing 1 or more fissures, and in adjacent intact regions. RESULTS.: Reductions in compressive stress within annulus fissures averaged 36% to 46%, and could have been greater at the fissure axis. Stress reductions were greater in degenerated discs, and were inversely related to nucleus pressure (R = 47%; P = 0.005). Safranin O stain intensity indicated that proteoglycan concentration was typically reduced by 40% at a distance of 600 μm from the fissure axis, and the width of the proteoglycan-depleted zone increased with age (P < 0.006; R = 0.29) and with general proteoglycan loss (P < 0.001; R = 0.32). Disrupted regions of annulus contained 36% to 54% less proteoglycans than adjacent intact regions from the same discs, although water content was reduced only slightly. CONCLUSION.: Annulus fissures provide a low-pressure microenvironment that allows focal proteoglycan loss, leaving a matrix that is conducive to nerve and blood vessel ingrowth.
    Spine 06/2012; 37(22):1883-91. DOI:10.1097/BRS.0b013e318263ba59
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    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2012; 27(6):1432; author reply 1433-4. DOI:10.1002/jbmr.1626
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