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Biomedical subjects

C B Sledge

Publications and source records attributed to C B Sledge.

At least 109 records · Page 6Linked to original sources

A tissue-culture model of cartilage breakdown in rheumatoid arthritis. Quantitative aspects of proteoglycan release.

1. The destruction of articular cartilage in human rheumatoid and other arthritides is the result of diverse mechanical, inflammatory and local cellular factors. A tissue-culture model for studying cartilage-synovial interactions that may be involved in the final common pathway of joint destruction is described. 2. Matrix breakdown was studied in vitro by using bovine nasal-cartilage discs cultivated in contact with synovium. Synovia were obtained from human and animal sources. Human tissue came from patients with ;classical' rheumatoid arthritis, and animal tissue from rabbits with antigen-induced arthritis. 3. Cartilage discs increased their proteoglycan content 2-3-fold during 8 days in culture. Proteoglycan was also released into culture medium, approx. 70% arising from cartilage breakdown. 4. Synovial explants from human rheumatoid and rabbit antigen-induced arthritis produced equivalent stimulation of proteoglycan release. After an initial lag phase, the breakdown rate rose abruptly to a maximum, resulting in a 2-fold increase of proteoglycan accumulation in culture medium after 8-10 days. 5. High-molecular-weight products shed into culture media were characterized chromatographically and by differential enzymic digestion. Proteoglycan-chondroitin sulphate accounted for 90% of the released polyanion, and its partial degradation in the presence of synovial explants was consistent with limited proteolytic cleavage. 6. Rheumatoid synovium applied to dead cartilage increased the basal rate of proteoglycan release. Living cartilage was capable of more extensive autolysis, even in the absence of synovium. However, optimal proteoglycan release required the interaction of living synovium with live cartilage. These findings support the view that a significant component of cartilage breakdown may be chondrocyte-mediated.

Animals↗

A tissue culture model of cartilage breakdown in rheumatoid arthritis. III. Effects of antirheumatic drugs.

The effects of hydrocortisone, indomethacin, and gold thiomalate on proteoglycan release were assessed in bovine nasal cartilage-rheumatoid synovium cocultures. Of the three agents, only hydrocortisone consistently inhibited both basal and synovium-stimulated cartilage breakdown. Hydrocortisone responsivity was a direct function of the degradative capacity of synovial specimens, and this was equally well demonstrated both in patients receiving long-term therapy and those given perioperative glucocorticoid therapy. The data are consistent with significant hydrocortisone inhibition of lysosomal enzyme-mediated degradation of cartilage.

Arthritis, Rheumatoid↗

Clinical study of total ankle replacement with gait analysis. A preliminary report.

Twenty-one ankle replacements in nineteen patients after an average follow-up of 14.7 months were analyzed with respect to their history, physical and roentgenographic findings, and gait analysis. The relief of pain and functional improvement after operation were disappointing compared with the results of prosthetic replacement in other joints and were not related to early complications, age, diagnosis, or the prosthesis used. Muscle weakness about the ankle, especially of the plantar flexors, was a prominent finding and appeared to cause abnormal patterns of gait and of ankle motion. The frequency of progressively increasing radiolucent lines was 88 per cent and of late loosening, 10 per cent. These results suggest a need for more emphasis on postoperative rehabilitation and on the uncertainty of this procedure at its present stage of development.

Activities of Daily Living↗

Total hip replacement with and without osteotomy of the greater trochanter. Clinical and biomechanical comparisons in the same patients.

Twelve patients with bilateral hip replacement, one side performed with a trochanteric osteotomy and the other without osteotomy, were analyzed by review of the clinical records, the findings on physical examination, preoperative and postoperative Harris hip scores, each patient's evaluation, biomechanical analysis of the preoperative and postoperative roentgenograms of the hips and pelvis, and force-plate gait analysis. All operations yielded good results clinically but the majority of patients preferred the replacement done without osteotomy. Blood loss and trochanteric bursitis were greater problems in patients who had an osteotomy. There were no differences between the two groups in the postoperative Harris scores or in the biomechanical measurements made on the preoperative and postoperative roentgenograms except for the change in the abductor-muscle length. Changes in this parameter correlated well with the patients' symptoms and clinical findings.

Adult↗

Experimental limb lengthening by epiphyseal distraction.

Kirshner wires were placed either side of the right distal femoral epiphysis and a constant tension device applied a distracting force across the plate in rabbits. Growth increase was measured between the wires and found to be about 150% greater than the concurrent normal growth between 2 control (undistracted) wires on the left; such growth increase can occur in the absence of fracturing. The forces required to do this were between 1/5 and 1/10 of those shown to cause fracturing in vitro. The growth increase was shown to be associated with hyperplasia and hypertrophy of the plate, as well as an increased rate of cell division and sulfated polysaccharide synthesis. This was in turn shown to be associated with an increase in new bone formation.

Animals↗

Complications of total hip-replacement arthorplasty in patients with rheumatoid arthritis.

During the period 1969 through 1974, 716 total hip-replacement arthorplasties were performed. The results of the surgery in 275 cases of rheumatoid arthritis as regards complications were compared with those in 382 procedures in cases of osteoarthritis. In contrast to the reports of others,the incidence of deep would infection in the two groups was found to be equal. Patients undergoing total hip-replacement arthroplasty as a revision of a previous operation had a substantially increased risk of infection. Patients with rheumatoid arthritis, however, were more subject to certain other complication (intraoperative fracture, difficulties with anesthesia, and malposition of prosthetic components), in addition to the complications that were predictable because of the involvement of multiple joints and the systemic disease process.

Adult↗