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Biomedical subjects

C B Sledge

Publications and source records attributed to C B Sledge.

At least 19 recordsLinked to original sources

Synovium-like tissue from loose joint replacement prosthesis: comparison of human material with a canine model.

The formation of synovium-like tissue is a biological response to a loose joint replacement prosthesis. Histological examination of this tissue has shown a synovial lining with a predominance of fibroblasts and macrophages, some multinucleated giant cells, and dispersed particles from the implant. Previous studies have reported elevated interleukin 1 (IL-1), prostaglandin E2 (PGE2), and collagenase in this tissue. We developed a canine model for the loose cemented femoral stem. Tissue harvested from the canine model was compared with human tissue retrieved at revision arthroplasty. Histology showed synovium, similar to that observed around loose human prostheses, adjacent to the canine cement sheath. Cells were isolated from this tissue and incubated in culture medium with or without naproxen for 3 days. Aliquots of the conditioned media were tested in the thymocyte proliferation assay to determine IL-1-like activity. IL-1 beta levels in human cell-conditioned media were analyzed by enzyme-linked immunosorbent assay, and PGE2 levels were measured by radioimmunoassay (RIA) using a PGE2 RIA kit (New England Nuclear). Human tissue contained levels of IL-1 beta in the range of 150 to 7,040 pg/mL and PGE2 levels of 82 to 952 ng/mL. The canine specimens contained IL-1-like activity and significant amounts of PGE2 (76 to 1,720 ng/mL). Naproxen decreased PGE2 levels in vitro. This animal model provides the means to investigate the in vivo and in vitro activity of the synovial cells around loose total joint prostheses.

Adult

Evaluation of the hip with pigmented villonodular synovitis. A case report.

Pigmented villonodular synovitis (PVNS) is an uncommon disorder of the synovium that rarely involves the hip joint. The natural history of an untreated case of PVNS is presented herein. A young adult with a painful hip and destructive changes on plain roentgenograms requires further diagnostic evaluation. The relative value of current imaging techniques is discussed in this report. Plain roentgenograms alone often suggest the correct diagnosis of PVNS of the hip, but traditional criteria have proven to be inaccurate. Computed tomography (CT) is helpful in demonstrating the location and degree of bone loss throughout the pelvis and assists in determining the need for bone graft or prosthetic modification in preoperative planning. Experience with magnetic resonance imaging (MRI) in this disorder is limited, but no clear advantage over CT has been demonstrated thus far. Three-dimensional reconstruction has provided no useful information not already found on plain CT or MRI. For diagnostic accuracy and effective preoperative planning, evaluation should include a complete blood count, sedimentation rate, CT scan, and MRI.

Adult

Chondrocyte mediated cartilage degradation: regulation by prostaglandin E2, cyclic AMP and interferon alpha.

Local responses to cytokines and their induced products play a critical role in outcome in the arthritic joint. Using a bovine nasal cartilage culture model, chondrocyte mediated breakdown was stimulated by lipopolysaccharides or tumor necrosis factor. Cartilage breakdown was inhibited in a dose dependent manner by prostaglandin E2, cyclic AMP enhancement and interferon alpha. The possible regulatory roles played by these agents in cytokine activated cartilage breakdown suggest potential therapeutic strategies in human arthritis.

Animals

Total hip arthroplasty in ankylosing spondylitis.

Total hip arthroplasty was performed on 29 hips in 19 patients diagnosed with ankylosing spondylitis over a 13-year period. The results were analyzed retrospectively with an average follow-up period of more than four years. Complete pain relief was achieved in 97%, and significant gains were made in ambulatory capacity. The limited gains in total range of motion (average improvement 75 degrees) were felt to be primarily due to the high incidence of Brooker Class III and IV myositis ossificans (23%) and long-standing soft tissue contractures.

Adult

Effects of isolated rheumatoid synovial cells on cartilage degradation in vitro.

Rheumatoid synovium in coculture with cartilage has been shown to release a factor(s) that stimulates the depletion of glycosaminoglycans (GAG) from cartilage matrix. Human rheumatoid synovium was enzymatically disaggregated and the isolated cells were subjected to a variety of mechanical and immunological treatments. Synovial cell conditioned media (SCCM) were prepared and analyzed for their ability to stimulate GAG depletion. SCCM prepared from increasing concentrations of isolated synovial cells demonstrated cartilage degradative activity in a dose-dependent manner. This activity was characterized as interleukin-1 like and was found mostly within the adherent cell population where the synovial macrophages retained significant degradative ability. T cells alone were found to have no direct degradative effect on cartilage, but their presence appeared to augment the response of the adherent cells. The techniques described here provide a quantitative model for examining the degradative factors from synovium as well as the cellular interactions that promote their release.

Animals

Rhenium heptasulfide: a potential carrier system for radiation synovectomy.

Rhenium sulfide colloid was prepared by the thiosulfate acid reduction method and assessed for its applicability as a particle carrier for use in radiation synovectomy. In vitro stability studies demonstrated that greater than 95% of the 186Re activity remained in colloidal form over a 5 day period. Intraarticular knee injections of 186Re2S7 into normal and arthritic rabbit joints were followed by gamma camera imaging and by biodistribution in order to quantify the leakage to different organs. Mean retentions of 186Re in knees, determined by gamma camera imaging were 97(+/- 4)%, 92(+/- 7)%, 89(+/- 9)% and 88(+/- 10)% at 1 h, 1, 2 and 3 days, respectively. The percent injected dose was 0.0023% in the lymph nodes, 1.65% in the liver, 0.006% to the spleen, 0.013% in the lungs, 0.35% in the kidney, 0.014% in the heart, 0.12% in the bone, 0.7% in the muscle, 0.3% in the fat and 0.6% in the blood.

Animals

Total shoulder arthroplasty versus hemiarthroplasty. Indications for glenoid resurfacing.

The results of total shoulder arthroplasty and hemiarthroplasty in a similar patient population were compared in an effort to define more clearly the indications for resurfacing the glenoid. The results of 64 Neer hemiarthroplasties in 59 patients were compared with 146 Neer total shoulder arthroplasties in 134 patients in a retrospective review of the period between 1974 and 1986. The average follow-up period was 44 months (range, 24-124 months). Hemiarthroplasty and total shoulder arthroplasty produced similar results in terms of functional improvement. Pain relief, range of motion, and patient satisfaction were better with total shoulder arthroplasty than hemiarthroplasty in the rheumatoid population. Progressive glenoid loosening was found in 12% of total should arthroplasties but no correlation with pain relief or range of motion was noted. Total shoulder arthroplasty is recommended for patients with inflammatory arthropathies, and hemiarthroplasty is recommended for patients with osteoarthritis, avascular necrosis, and four-part fractures with preservation of glenoid congruity and absent synovitis.

Adult

Antibody to interleukin 1 inhibits the cartilage degradative and thymocyte proliferative actions of rheumatoid synovial culture medium.

Cartilage breakdown in rheumatoid arthritis results from (a) lytic action by synovial enzymes, and (b) release of synovial catabolin, now believed to be a form of interleukin 1 (IL-1), causing chondrocytes to degrade their matrix. Rheumatoid synovial culture media were tested for their ability to stimulate cartilage degradation (proteoglycan release from bovine nasal cartilage discs) and thymocyte proliferation (3H-thymidine incorporation) in the absence or presence of anti-IL-1. Degradation of living cartilage, stimulated 2-fold by synovial culture media, was inhibited up to 80% by anti-IL-1. Residual breakdown in living cartilage and synovial culture media induced breakdown in dead cultures were of similar magnitude, and both were unaffected by antibody treatment. Proteoglycan products released from synovial culture media treated cartilage were of smaller average molecular weight (Sepharose CL-2B), and such size reduction was inhibited by anti-IL-1 treatment. Synovial culture media that stimulated cartilage degradation also stimulated thymocyte proliferation; the latter was fully suppressible by anti-IL-1. One of 8 synovial culture media contained an inhibitor(s) of thymocyte proliferation, removable by dialysis. We conclude (1) rheumatoid synovial catabolin activity is due to a form of IL-1. (2) A minor nonsuppressible component of synovial culture media stimulated breakdown, identical in living and killed cartilage, is due to passive transfer of enzymic activity. (3) Cultured rheumatoid synovium releases both IL-1 and an inhibitor(s) of IL-1 action.

Antibodies

Biochemical and histological evaluation of the synovial-like tissue around failed (loose) total joint replacement prostheses in human subjects and a canine model.

The tissue around loose total joint replacement prostheses displays a synovial-like lining comprised of cells that produce IL-1 and PGE2, mediators of inflammation that stimulate bone resorption. Particles of titanium alloy, as well as cobalt-chromium alloy and polyethylene, were found to aggravate the histiocytic response and production of IL-1 and PGE2. Tissue with similar histological and biochemical features was produced in a canine model of the aseptic loose cemented femoral stem.

Animals

Tissue changes around loose prostheses. A canine model to investigate the effects of an antiinflammatory agent.

The aseptically loosened prosthesis provided a means for investigating the in vivo and in vitro activity of the cells associated with the loosening process in seven dogs. The cells were isolated and maintained in culture for sufficient periods of time so that their biologic activity could be studied as well as the effect of different agents added to the cells in vivo or in vitro. The biologic response as determined by interleukin-1 and prostaglandin E2 activity paralleled the roentgenographic appearance of loosening and the technetium images and observations made at the time of revision surgery. The correlation between clinical, roentgenographic, histologic, and biochemical loosening indicates that the canine model is suitable for investigating the mechanisms of prosthetic failure. A canine model permits the study of possible nonsurgical therapeutic interventions with the ultimate hope of stopping or slowing the loosening process.

Animals

Results of revision total knee arthroplasty performed for aseptic loosening.

One hundred thirty-seven revision total knee arthroplasties (TKA) performed in 117 patients with failed aseptic metal-to-plastic knees over ten years (1974-1984) were studied to determine the long-term clinical and roentgenographic results and were compared to primary TKA. The mean age was 65 years (range, 32-90 years). Fifty-three percent had rheumatoid arthritis, and 47% had osteoarthritis. The mean interval from initial to revision TKA (129 knees) was four years (range, three months to 11 years) and from the first to second revision (seven knees) was 2.4 years (range, seven months to 5.5 years). The most common reasons for failure were loosening (73%), patellar complications (13%), and instability (10%). The mean follow-up time was 5.2 years (range, two to 12 years). Function, instability, motion, and pain all improved after revision TKA, but these improvements were significantly less than those seen after primary TKA. One-third of the patients still ambulated with crutches, a walker, or not at all. While mean postoperative flexion was 100 degrees, 24% could not flex to 90 degrees. Most patients (90%) were malaligned at the time of failure and remained so after revision (78%). The increased incidence of radiolucent lines (tibial, 61%; femoral, 24%) was not related to increased failure. Complications were not increased over primary TKA. The failure rate was 5.8% at 5.2 years, or approximately 1% per year. A successful clinical result was defined as a knee with mild or no pain, mild or no instability, and flexion to at least 90 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Total knee arthroplasty with the kinematic prosthesis. Results after five to nine years: a follow-up note.

A review of the results of 192 kinematic total knee replacements five to nine years after the operation showed that the results were still satisfactory. At the time of the review, the ages of the patients ranged from twenty-two to eighty-seven years. About half of the patients had rheumatoid arthritis and the other half, osteoarthrosis. About 90 per cent of the results were rated good or excellent, and the average range of flexion was 109 degrees. Radiolucency was present around 40 per cent of the tibial components, 30 per cent of the femoral components, and 60 per cent of the patellar components, but the lines were thin and not progressive. The complications included loosening of the patellar components in five knees, one fracture of the tibial tray with loosening of the patellar component, one fracture of the patellar component, and one dislocation of the patellar component.

Adult

Cyclic AMP-regulating agents inhibit endotoxin-mediated cartilage degradation.

The influence of cyclic AMP on cartilage degradation was investigated by using phosphodiesterase inhibitors [theophylline and 3-isobutyl-1-methylxanthine (IBMX)], forskolin (which activates the catalytic subunit of adenylate cyclase) and cyclic AMP analogues (dibutyryl and 8-bromo). Breakdown was assessed by quantification of proteoglycans released into the media of 8-day bovine nasal-septum cartilage cultures. Theophylline (1-20 mM), IBMX (0.01-2 mM) and dibutyryl cyclic AMP (0.1-2 mM) had little or no influence on the rate of proteoglycan release from unstimulated (no-endotoxin) cartilages. A small but detectable increase in breakdown was observed with 8-bromo cyclic AMP (0.5-2 mM) and forskolin (50-75 micrograms/ml). To examine potential inhibitory influences of these agents, the cyclic AMP modulators were added to cultures simultaneously treated with Salmonella typhosa endotoxin (12-25 micrograms/ml), a potent stimulator of cartilage degradation. The 3-4-fold stimulation of breakdown by endotoxin was strikingly inhibited by all three classes of cyclic AMP regulators. Optimal inhibition was found at 10-20 mM-theophylline, 1-2 mM-IBMX, 50-75 micrograms of forskolin/ml, 2 mM-dibutyryl cyclic AMP and 2 mM-8-bromo cyclic AMP. Inhibition was shown to be reversible, indicating that cartilages were viable after treatment. Sepharose CL-2B chromatography of proteoglycan products released from treated cartilages showed that the endotoxin-stimulated shift to lower average Mr was significantly prevented by cyclic AMP analogues and phosphodiesterase inhibitors. Together, these results show that agents which increase cyclic AMP inhibit both quantitative and qualitative aspects of endotoxin-mediated cartilage degradation.

1-Methyl-3-isobutylxanthine