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Research Interests: Humans, Tibia, Femur, Female, Male, and 3 moreClinical Sciences, Knee Osteoarthritis, and Knee Joint
A possible role for immune complexes in the degradation of cartilage (rheumatoid arthritis and antigen induced arthritis) has been modelled in vitro by studying interactions between cultured bovine chondrocytes and monomeric (M) or heat... more
A possible role for immune complexes in the degradation of cartilage (rheumatoid arthritis and antigen induced arthritis) has been modelled in vitro by studying interactions between cultured bovine chondrocytes and monomeric (M) or heat aggregated (HA) IgG. Concentrations of IgG used were within the range of values reported in the synovial fluids of rheumatoid joints. ELISA and rosetting assays revealed Fc receptor mediated binding of MIgG and HAIgG to chondrocytes that had been cultured, but not to freshly isolated cells. Both forms of IgG stimulated the production of metalloprotease, but only HAIgG boosted generation of superoxide anion and reduced proteoglycan synthesis. HAIgG also stimulated cells to produce immunoreactive interleukin 1 although no biological activity was apparent. It is concluded that the equivalent behavior of chondrocytes in vivo, triggered by immune complexes, could contribute or lead directly to matrix degradation.
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Our recommendations for standing radiography of the lower limb are that assessments be standardized with respect to limb rotation and fixed relative positions of the hip, knee, and ankle. Specifically, a neutral knee rotation position... more
Our recommendations for standing radiography of the lower limb are that assessments be standardized with respect to limb rotation and fixed relative positions of the hip, knee, and ankle. Specifically, a neutral knee rotation position should be set up, defined as alignment of the flexion plane straight ahead. For a complete appraisal, there should be both AP and lateral views in which the positioning of the patient is the same in all respects. The QPR frame greatly assists in achieving these objectives. Furthermore, the presence of a calibration system adds to the reliability and reproducibility of data by compensating for errors of position or alignment arising from the placement of the source and the film. Standardization of positioning also improves the detectability of axial-rotational deformities on comparison of AP and lateral views, providing more reliable indications of the need for CT than possible with nonstandardized short views. When a skyline patellar radiograph is adde...
Research Interests: Adolescent, Osteoarthritis, Humans, Female, Male, and 4 moreClinical Sciences, Adult, Reference Values, and Knee Joint
Some arthritic knees with varus deformity show excessive valgus angulation of the femoral joint surface with proximal tibia vara. This causes a downward and medial inclination of the articular surfaces in the coronal plane. The patients... more
Some arthritic knees with varus deformity show excessive valgus angulation of the femoral joint surface with proximal tibia vara. This causes a downward and medial inclination of the articular surfaces in the coronal plane. The patients we studied had a medial shift of the standing load-bearing axis, and arthritic changes mainly in the medial compartment. Some also had lateral tibial subluxation with twisting of the distal femur and proximal tibia in opposite directions. We assessed the articular geometry by precise radiographic analysis, and compared the results with those in normal volunteers and a group of osteoarthritic patients. The prevalence of this type of deformity in our osteoarthritic patients was 11.5%; its recognition allows the use of specific operative correction that may include double osteotomy or the precise orientation of prosthetic components.
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A method is described which provides standardised reproducible radiographic images of the lower limb. Anteroposterior and lateral radiographs are digitised and processed by computer to provide graphic/numeric displays of angles and linear... more
A method is described which provides standardised reproducible radiographic images of the lower limb. Anteroposterior and lateral radiographs are digitised and processed by computer to provide graphic/numeric displays of angles and linear measurements, relating the centre points of the hip, knee, and ankle. Two cases illustrate how surgical planning is facilitated when standardised data are available. These data confirm the close relationship between postoperative limb alignment and positioning of prosthetic elements.
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Cartilage from patients with rheumatoid arthritis and from animals with antigen-induced arthritis is frequently contaminated with complement-containing immune complexes. A possible role for complement activation in cartilage degradation... more
Cartilage from patients with rheumatoid arthritis and from animals with antigen-induced arthritis is frequently contaminated with complement-containing immune complexes. A possible role for complement activation in cartilage degradation was modeled in vitro by exposing cultured bovine chondrocytes to homologous serum, and determining cytotoxicity by monitoring the release of intracellular 51Cr. Complement activation was found to be cytotoxic, having maximal effect at 20-30% serum by 18 h. Serum toxicity was ablated by heat (50 degrees C, 20 min) or methylamine treatment but not by EGTA, suggesting that in these experiments activation occurred by the alternate route. The implications of the results are discussed in relation to ultrastructural evidence for the involvement of complement in the pathogenesis of cartilage degradation in inflammatory arthritis.
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Rabbits were first immunized and later challenged with the same antigen (bovine serum albumin, or ferritin) by injection into the tibialis anterior tendon. Inflammatory changes of the tenosynovium and epitenon included infiltration by... more
Rabbits were first immunized and later challenged with the same antigen (bovine serum albumin, or ferritin) by injection into the tibialis anterior tendon. Inflammatory changes of the tenosynovium and epitenon included infiltration by neutrophils (early) and mononuclear cells (later) over a 6-week course of tenosynovitis. A pattern of antigen entrapment in the tendon together with immunoglobulin was shown by use of radiolabelled antigen and immunochemical staining. Half-life of antigen in the tissues averaged 5 days over the 6-week period. Changes in the epitenon included cellular necrosis, appearance of phagocytic cells, and disruption of the collagen matrix. Tissues of control animals (challenged without prior immunization) showed minimal changes and significantly less retention of antigen (P greater than 0.005). The model is relevant to the mechanism of tendon damage associated with antigen-driven chronic inflammation, as may be the case in rheumatoid arthritis.
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The critical role of CMI in the pathogenesis of RA has been reinforced, if not entirely illuminated, by recent information about the immunogenetic basis for individual susceptibility, in regard to genes of the HLA-D locus that control... more
The critical role of CMI in the pathogenesis of RA has been reinforced, if not entirely illuminated, by recent information about the immunogenetic basis for individual susceptibility, in regard to genes of the HLA-D locus that control expression of MHC II determinants. An aberration in the T-cell response to cells presenting antigen is strongly implied, and must therefore be characterized. We will need to know what types of antigen trigger aberrant responses in those that are susceptible, and whether continuous presence of antigen is necessary to sustain chronic inflammation. The second part of this article will review immunological injury to joint tissues as an off-shoot of the CMI and HI responses of RA. Using data from animal models we shall examine criteria for establishing chronic joint inflammation, and consider their relevance to RA. We shall also consider the problem of why some joints are more susceptible than others to immunological injury.
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ABSTRACT The visible reaction occurring at a uranium surface exposed to 700 mm hydrogen at 170°C was observed under the microscope. Initial attack was localized and of two types: one readily visible and developing randomly at inclusion... more
ABSTRACT The visible reaction occurring at a uranium surface exposed to 700 mm hydrogen at 170°C was observed under the microscope. Initial attack was localized and of two types: one readily visible and developing randomly at inclusion sites, the other seen only at relatively high magnification developing with uniform distribution. Rates of formation of attack sites of both types on clean uranium were found to be high. With increasing thickness of oxide film up to 1000 Å rates were progressively lower. It is proposed that attack sites are formed at local deficiencies in the oxide film around inclusions and through film porosity.