EVALUATION OF DMSO TRANSPORT IN HUMAN ARTICULAR CARTILAGE: VEHICLE SOLUTIONS AND EFFECTS ON CELL FUNCTION.

Osteochondral allografting techniques are limited by the availability of suitable donor tissue; there is an urgent need for effective cryopreservation. A fundamental requirement is the need to establish initial conditions of exposure to cryoprotectant that the chondrocytes will tolerate and that load the tissue with an adequate concentration of cryoprotectant. Three vehicle solutions to transport DMSO into the tissue were studied. Knee joints were obtained from deceased donors with appropriate consent. Whole condyles were treated with 20% w/w DMSO in each of three vehicle solutions and chondrocyte function and tissue CPA content measured. The results showed that exposure to 20% DMSO in each vehicle solution for 2 hours at 0 degrees C was tolerated without loss of GAG synthetic activity. It was observed that penetration of DMSO increased little after 1 hour of CPA exposure at 0 degrees C but the final tissue concentration of CPA was markedly lower than that in the medium.

A liquidus tracking approach to the cryopreservation of human cartilage allografts.

In the "liquidus tracking" (LT) approach to cryopreservation both the temperature and the concentration of cryoprotectant (CPA) are controlled such that solution composition "tracks" the liquidus (melting point) line for that system. Ice crystal formation is prevented but the tissue is not exposed to CPA concentrations exceeding those experienced by cells during conventional cryopreservation. This approach is particularly appropriate for articular cartilage because chondrocytes in situ are exquisitely susceptible to damage by the crystallisation of ice. This project aimed to develop a suitable process for tissue to be used in the surgical repair of damaged human knee joints. A high proportion of the chondrocytes should be alive. Human articular cartilage was obtained from deceased donors and dimethyl sulphoxide (DMSO) was used as the CPA, cooling was at 0.14°C/min and warming at 0.42°C/min. The vehicle solution was CPTes2. A program of increasing DMSO concentration was developed for cooling and this gave satisfactory tissue concentrations but reduction of DMSO concentration during warming was inadequate, resulting in higher tissue concentrations than required. Biomechanical testing indicated a compressive modulus of 9.5±1.3 MPa in LT-processed cartilage, with control values of 11.6±0.8 MPa (p>0.05, Student's t-test). Measurement of GAG synthesis sometimes approached 65% or 85% of control, but the variability of replicate data prevented firm conclusions. Ideally allograft tissue should score 1A or above on the Noyes scale and the donor age should be less than 46 years but the cartilage used in this study did not meet these standards.

Preliminary experience with diacetylrhein in the treatment of osteoarthritis.

A single-blind, placebo controlled study was carried out over a 12-week period in 12 patients with osteoarthritis of the hip or knee to assess the effectiveness of 50 mg diacetylrhein per day. The 4 weeks of active treatment were preceded and followed by periods on placebo. Response to treatment as assessed by pain score, walking time and the number of 'rescue' analgesic tablets (paracetamol) consumed showed that 6 patients improved, 4 were unchanged and 2 deteriorated. Improvement was not apparent for several weeks after starting active treatment and remission lasted for 2 weeks to 3 or more months after the drug was withdrawn. The action of diacetylrhein is not yet established, but it does not appear to be related to analgesia or inhibition of prostaglandin synthetase activity. It is considered that further studies of this interesting drug are warranted to determine the most effective dose and duration of treatment.

Myelotoxicity of D-penicillamine.

Information has been collected on 10 patients, 9 with marrow depression and 1 in whom the diagnosis was presumed. Six of the 10 patients died. The sequentially recorded blood counts on at least 5 of the patients showed a downward trend of the white cell and platelet counts while D-penicillamine was still being administered. One patient suddenly developed leucopenia and thrombocytopenia with a streptococcal septicaemia.

Management of the rheumatoid hand.

The hand is often forgotten in the management of rheumatoid arthritis. Rheumatoid disease in the hand, as elsewhere, can be divided into three phases: the early proliferative stage, the period of synovial regression and the stage of fixed deformity. Our studies suggest that the eventual pattern of hand deformity is related to the site, severity and sequence of synovial involvement. It is, therefore, likely that the results of early medical and surgical treatment of the rheumatoid hand will be more rewarding than those of late reconstructive procedures.

Experience with Silastic prostheses in the rheumatoid hand. A 5-year follow-up.

Nine patients with rheumatoid arthritis, who had Silastic prostheses (Swanson's) introduced into 34 metacarpophalangeal joints, were reviewed 5 years after surgery. The most important long-term advantage conferred by the introduction of prostheses was pain relief; functional benefit was marginal. The majority of prostheses eventually fractured but this did not necessarily lead to a functional deterioration. Impairment of function was usually the result of loss of flexion at the metacarpophalangeal joints, but it was sometimes due to excessive instability after fracture of the prostheses. It is suggested that Silastic joint replacement may be a worthwhile procedure in rheumatoid patients with moderate destruction or deformity of the metacarpophalangeal joints when pain is a predominant feature. Significant functional improvement can be anticipated only when secondary to pain relief.

Monitoring adverse reactions to antirheumatic drugs.

Drug monitoring systems have been developed in response to public concern over drug-related adverse events: no completely satisfactory method has yet been developed. Drug associated morbidity and mortality is a major problem in the treatment of rheumatic diseases. The damage to patients from recognized drug hazards can be reduced by close monitoring and sequential recording of results of investigations. Previously unrecognized drug-associated adverse events can best be identified by prospective surveillance of new drugs. Methodological problems are considerable but not insurmountable. Rheumatologists need to apply a variety of strategies to drug monitoring, some of them involving international cooperation.

Myelotoxicity of gold.

Of 55 patients who developed blood dyscrasias attributable to gold treatment 15 with bone marrow hypoplasia died. A few of the dyscrasias, occurring in patients who had taken a low total dose of sodium aurothiomalate, may have resulted from immune hypersensitivity, but most, occurring in patients who had taken a higher total dose, were due to cumulative toxicity. All patients receiving gold treatment should undergo frequent blood counts. Any pronounced or continuing fall in the counts is a warning of toxicity, and gold treatment should be stopped. Treatment should be resumed only with caution, and in some patients already in remission lower doses may be just as effective in controlling the disease.