Biomedical subjects
Publications and source records attributed to E C Huskisson.
Three double-blind crossover trials were used to study the effects of single doses of flurbiprofen at night on pain at night, duration of morning stiffness and sleep disturbance in patients with active rheumatoid arthritis. Flurbiprofen (150 mg) was shown to be superior to placebo and 150 mg was no more effective than 100 mg. Serum levels of the drug were significantly higher with 150 mg but did not correlate with clinical effects.
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Ninety patients with rheumatoid arthritis completed a double-blind crossover trial comparing fenoprofen, ibuprofen, ketoprofen, and naproxen. Fenoprofen and naproxen were slightly more effective than the other two drugs but there were striking individual variations in response. Groups of patients could be identified who preferred each of the four drugs. The commonest side effects were those related to the upper gastrointestinal tract; these showed individual variation and seldom occurred with more than one or two of the drugs. Side effects were least common with ibuprofen and naproxen. Since naproxen combined greater effectiveness with a lower incidence of side effects it must be regarded as the first choice among these drugs. It may be necessary to try several drugs before finding the right one for a particular patient.
In a controlled study involving thirty-four patients levamisole was shown to be as effective as D-penicillamine and more effective than placebo in the treatment of rheumatoid arthritis. Its action was slow and was accompanied by a reduction in erythrocyte sedimentation-rate, rheumatoid factor, and technetium index. These properties indicate that it has a specific action like that of D-penicillamine. Stimulation of cell-mediated immunity was evident in patients treated with levamisole, and there was a correlation between such changes and pain relief. Animal models confirmed the absence of anti-inflammatory effect and provided some evidence of enhancement of cell-mediated immunity and macrophage stimulation.
A method for identifying particles of crystalline calcium hydroxyapatite in synovial fluids and biopsy material has been developed with high-resolution scanning electron microscopy and an energy-dispersive micro-analytical system. Particles of hydroxyapatite were identified in the joints of six patients diagnosed as having osteoarthritis, three of whom had acute inflammatory episodes with effusions into the joints. Apatite was not identified in joints affected by rheumatoid arthritis and other types of arthropathy. Animal studies showed that hydroxyapatic crystals can cause an acute inflammatory reaction, and this has been confirmed by experimental studies in man. It is suggested that a third type of crystal-deposition disease should be recognised--namely, calcium-hydroxyapatite crystal-deposition disease.
A delayed hypersensitivity response was induced in the rat paw using pertussis vaccine. Oedema was measured after the challenging injection. D-penicillamine and levamisole enhanced the response, while indomethacin suppressed it. This model is useful to distinguish the effects of anti-inflammatory drugs from those like D-Penicillamine which have a specific activity in rheumatoid arthritis.
Male Wistar rats have been sensitized to Bordetella pertussis using a mixture of Freund's incomplete adjuvant and pertussis organisms. Intrapleural challenge 12 days later with pertussis produced a marked delayed inflammatory response, maximal at 48 hours and dominated by influx of mononuclear cells. Dosing with D-penicillamine (25 mg/kg) and levamisole (5 mg/kg) at the time of challenge produced a significant enhancement of the reaction. A long period of dosing with either drug, or treatment with indomethacin (3 mg/kg), suppressed the response. The relevance of this to the testing and mode of action of antirheumatic drugs is discussed.
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Visual-analogue scales can be used to measure the subjective aspect of functional ability but, in a group of patients with severe rheumatoid arthritis, the severity of impairment of two predetermined functional tests was low in comparison with the severity of pain. Measurements of the ability to carry out these two functions, using visual-analogue and descriptive scales, and also using the time taken to perform the tasks, were not useful measures of the effectiveness of treatment of rheumatoid arthritis. Poor correlations were obtained between different measures of the same function and between different functions measured in the same way.
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In an apparently double blind crossover study, two experienced measurement technicians were able to identify many of the treatment periods. They most often correctly identified aspirin, a drug with prominent effects and side effects. It is argued that in many circumstances it is better to use a blind observer who is not concerned with the giving of treatment or the collection of side effects.
The technetium index was measured in 22 patients with rheumatoid arthritis, before and after 6 months' treatment either with penicillamine or with anti-inflammatory drugs. The index was calculated by dividing the sum of the count rates over both knees and both wrists by the dose of technetium given. In the penicillamine group there was a significant reduction in the technetium index and the changes correlated well with some clinical measurements of improvement. It is suggested that the technetium index is a useful objective measure of the effects of drugs with a specific activity in rheumatoid arthritis.
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