Nonarthritic Knees Research Articles

Suppression of antigen-induced arthritis in rabbits by ex vivo gene therapy.

Gene therapy offers a novel approach to treating human joint diseases such as rheumatoid arthritis. In the present study, we have used the retrovirus, MFG-IRAP, to transfer the human IL-1 receptor antagonist protein (IRAP) gene to rabbits' knees and have assessed its impact on inflammatory and chondrodestructive aspects of the acute phase of antigen-induced arthritis in these joints. Surprisingly, intra-articular expression of IRAP was three- to fivefold higher in arthritic knees than in nonarthritic knees, accumulating to levels of over 20 ng/knee in the highest expressing joints. This level of expression produced a marked chondroprotective effect but a milder anti-inflammatory one. Both the increased cartilage matrix catabolism and the inhibition of matrix synthesis that occur in antigen-induced arthritis were abrogated in the presence of the IRAP gene; the latter effect was particularly strong. Of the indices of inflammation that were examined, only leukocyte influx into the joint space was inhibited, and this effect declined with time. Concentrations of rabbit IL-1 were reduced by the IRAP gene, suggesting inhibition of an autocrine induction loop. These data demonstrate that the course of arthritic disease in the rabbit knee can be altered by genetic manipulation, thus encouraging the further development of gene treatments for human joint diseases.

Accuracy and precision of joint space width measurements in standard and macroradiographs of osteoarthritic knees.

To improve the reproducibility and accuracy of joint space width (JSW) measurement as an assessment of cartilage loss in patients with osteoarthritis (OA) of the knee by determining how precision and accuracy of JSW measurement were altered by a computerised method of measurement, correction for radiographic magnification, radiography of the knee in the standing semiflexed view, and high definition macroradiography of the knee in the semiflexed view--taking JSW measurements from standard radiographs of OA knees in the extended view as the standard for comparison. Twenty five OA and 10 nonarthritic knees were radiographed in the extended view and minimum JSW was measured manually. Conventional and x5 macroradiographs were taken in the semiflexed view. All radiographs were taken twice on the same day and repeated two weeks later. Automated computerised measurement of minimum JSW was obtained from digitally stored images of all radiographs. For medial compartment JSW measurements, computerised was more accurate than manual, correction for radiographic magnification improved precision and accuracy, measurements in the semiflexed view were more precise and accurate, and macroradiography increased measurement precision. For the lateral compartment JSW measurements, correction for radiographic magnification improved precision and accuracy, and the semiflexed view improved precision only. Protocols defining radiographic and mensural procedures are essential for quality control of knee radiography in the semiflexed view to permit accurate and reproducible measurement of JSW. Macroradiography provides greater precision of JSW measurement.

Detectable levels of pyridinoline are present in synovial fluid from various patients with knee effusion: preliminary results*

There is a major interest for using biochemical markers of bone metabolism as a non-invasive tool for diagnostic purposes in the field of bone and joint diseases. Based upon the fact that the pyridinium cross-links of collagen are markers of bone and cartilage degradation, this study was designed to assess the presence of pyridinoline in synovial fluid samples originating from various arthritic and non-arthritic knee joints. Using a sample pooling method, significant levels of pyridinoline could be measured in synovial fluid by high performance liquid chromatography. Pyridinoline levels ranged from 19.3 +/- 5.8 pmol mL-1 (mean +/- SD) in osteoarthritic knee joints up to 32.4 +/- 14.6 pmol mL-1 in rheumatoid arthritis joints. Pyridinoline levels in synovial fluid were not significantly correlated to disease duration and synovial fluid cell count, but were correlated to erythrocyte sedimentation rate in osteoarthritic patients (r = 0.99, P = 0.002). This study demonstrates that synovial fluid originating from knee effusion contains significant levels of pyridinoline which can be quantified by high performance liquid chromatography and could, therefore, be a tool to investigate the metabolism of a single joint.

Cysts of the medial meniscus. Arthroscopic diagnosis and management.

We report the clinical and arthroscopic findings in 20 cases of medial meniscal cyst with a mean follow-up of 20 months. These were studied prospectively from a series of 7435 knee arthroscopies in which there were 1246 stable non-arthritic knees with medial meniscal tears. The diagnosis on referral was incorrect in seven, and incomplete in seven. There was coexistent meniscal injury in 17 (85%), but in the other three no tear was visible at arthroscopy. Ten knees had additional intra-articular abnormalities. Treatment of the cyst was by open resection in 12 and arthroscopic evaluation at meniscectomy in seven. In one case the cyst resolved after arthroscopic partial meniscectomy alone. Meniscal tears were treated by arthroscopic partial medial meniscectomy. Medial meniscal cysts are an important but under-diagnosed cause of knee pain and are frequently related to arthroscopically diagnosable and treatable meniscal pathology. Treatment should be directed towards both the meniscus and the cyst, which may require open surgery.

Inorganic pyrophosphate in metabolic diseases predisposing to calcium pyrophosphate dihydrate crystal deposition.

Inorganic pyrophosphate (PPi) levels were estimated by radiometric assay in urine and in synovial fluid (SF) from asymptomatic, nonarthritic knees of patients with untreated metabolic disease and normal controls. SF PPi was significantly elevated in patients with hyperparathyroidism (mean +/- SEM 19 +/- 3 microM; n = 9), hemochromatosis (23 +/- 5 microM; n = 6), and hypomagnesemia (27 +/- 0.1 microM; n = 2) compared with normal subjects (10 +/- 0.5 microM, n = 50), and was low in patients with hypothyroidism (4.2 +/- 2.3 microM; n = 11) (P less than 0.05 all comparisons). Urinary PPi was elevated only in those with hypophosphatasia. Local elevation of ionic PPi may be relevant to the mechanism of crystal formation in metabolic diseases predisposing to calcium pyrophosphate dihydrate (CPPD) crystal deposition. The finding of low SF PPi levels in patients with hypothyroidism further questions the association between this condition and CPPD.