Biomedical subjects
Publications and source records attributed to H Sheppeard.
A patient is described with longstanding ankylosing spondylitis, who develops radicular pain and neurological abnormalities. The diagnosis was cauda equina syndrome. This diagnosis was made on the basis of the clinical findings and the appearance of the computed tomography scan.
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Unlike other areas of research into arthritis, it is pleasing to record independent work leading to convergence of ideas instead of divergence and increasing complexity. Catabolin is now identified with interleukin-1, although there is case for the retention of the original name to describe its chondrocyte-stimulating function with subsequent matrix degradation. In 10 years, catabolin/interleukin-1 research has yielded much information about cellular interactions within the arthritic joint and has provided a probe with which the intricacies of matrix metabolism are being unravelled. In future, there are prospects of characterizing the naturally occurring inhibitors and developing new compounds which influence the actions of catabolin/IL-1 to the benefit of the patient with arthritis.
Five hundred new patients seen at a rheumatology clinic during the first three years of specialist practice were categorised according to diagnosis, age and sex, source of referral, geography of referral and follow up data. Degenerative joint disease was diagnosed in 33.4% of patients; inflammatory joint diseases in 29.4% and soft tissue rheumatism in 9.4%. Connective tissue diseases were rarely encountered (2%) and in 10.4% of patients the diagnosis was uncertain or undetermined. The age range was 6 to 85 years and the mean age 46. Sixty-nine percent of patients were women. General practitioners referred 85.2% of patients and 57.2% of the total patients seen lived within 20 km of the hospital, an area containing approximately 84,000 people. After three years all patients with inflammatory joint diseases and connective tissue diseases were still attending the follow-up clinic compared to 40% of those with non-inflammatory joint diseases. From the data collected, only a small percentage of patients with rheumatic complaints in the community were referred to the clinic and the dichotomy between academic and practical rheumatology was apparent.
A selection of NSAID's and diphosphonates were studied in a tissue culture model of cartilage degradation utilising porcine synovium and bovine nasal cartilage. All the NSAID's significantly reduced cartilage degradation when incorporated into the synovial culture medium. Lesser reductions were recorded when preformed chondrocyte stimulating factors were used and NSAID's added at the cartilage assay stage. These findings suggested that the principle site of action of NSAID's is upon the production of chondrocyte stimulating factors. None of the NSAID's tested affected inherent cartilage degradation. Diphosphonates had the opposite effects, they increased inherent cartilage degradation but had no effect on chondrocyte mediated cartilage degradation. The relationship of these results to previous known effects of NSAID's and diphosphonates upon cartilage is discussed. In addition, correlations between chondrocyte stimulating factors, catabolin and interleukin 1 are made.
1 Synovial cells produce a protein factor, catabolin, that induces chondrocytes to resorb their own matrix with the release of glycosaminoglycan (GAG). 2 Studies were performed to determine the effect of isoxicam, a new NSAID, on GAG production in a catabolin system utilizing tissue culture of bovine nasal septum in a medium containing pooled synovial tissue from young pigs. 3 Using fresh medium containing no synovial tissue, the release of GAG by inherent cartilage breakdown was 49.7% after 8 days culture. GAG release at 8 days increased to 83.6% by the addition of synovial cells to the culture medium, due to the action of catabolin. 4 The incorporation of isoxicam, at concentrations from 5-30 micrograms ml-1, in the porcine synovial culture medium significantly reduced the GAG release to 70.9%. 5 Isoxicam at 50 micrograms ml-1 added to fresh medium without synovial tissue had no effect on cartilage breakdown or GAG production. 6 The results of these experiments show that isoxicam is unlikely to impair cartilage metabolism and may even decrease cartilage resorption.
Pain-mood relationships were investigated in 23 patients with long-standing rheumatoid arthritis over a two-week period. Patients completed form B of the Eysenck personality inventory on entry to the study and visual analogue scales for pain, anxiety and sadness daily throughout the study period. Two pain-mood relationships were identified: a synchronous relationship in which pain and mood scores were positively correlated and an asynchronous relationship in which pain and mood scores were uncorrelated. Furthermore, in all patients reporting high pain and showing synchronous relationships, the pain and mood scores were similar in magnitude, while in all patients reporting high pain and showing asynchronous relationships, the pain and mood scores were dissimilar in magnitude. The latter patients remained calm and happy despite severe pain. All patients reporting low pain showed synchronous and close relationships between pain and mood. Extraversion, neuroticism, age, duration and severity of disease were unrelated to pain severity and the pain-mood relationships recorded. The asynchronous pain-mood relationship was attributed to a coping response to severe pain. Patient education combined with physical, psychological and pharmacological treatments might induce such a response in patients unable to cope with chronic pain.
Use of pain rating scales, especially the visual analogue scale (VAS), has increased dramatically in the last decade. Consideration of the VAS in terms of its physical structure and the patient's behaviour when confronted with the scale, casts doubt on its validity. It is non-linear and prone to bias which limits its use as a serial measure of pain severity. Measuring pain intensity alone imposes further limitations. The McGill Pain Questionnaire measuring several dimensions of pain appears to be a better alternative.
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The analgesic effects of high frequency transcutaneous electrical nerve stimulation (TNS), "acupuncture-like" TNS and placebo TNS were evaluated in 33 patients with rheumatoid arthritis and chronic hand pain using a randomized, double-blind, non-crossover design. An oscilloscope was employed to monitor the stimulator output in the TNS treatment groups and to provide strong suggestion and a focus of attention in the placebo treatment group. The two forms of TNS were applied at the highest intensity that could be tolerated by patients. Assessments of resting pain, joint tenderness, grip strength and grip pain were made before and after treatment. The pain and joint tenderness measurements showed high frequency TNS, "acupuncture-like" TNS and placebo TNS to be equally effective in producing analgesia of similar degree and trend over time. The grip strength measurements showed no significant change. The results obtained with placebo are probably due to the suggestion and attention effects of the visual stimulus. The implications of these results in respect to pain control pathways are discussed. Although TNS given at high intensity was shown to be no better than placebo applied with strong suggestion, this does not preclude its use as a method of pain control in rheumatoid arthritis.
A patient is described whose initial symptoms, though suggestive of polymyalgia rheumatica, were attributed to psoriatic arthritis, and whose subsequent development of claudication of the left arm led to the biopsy proven diagnosis of giant cell arteritis. Attention is drawn to widespread arterial involvement by giant cell arteritis which, though uncommon, must be considered in all patients with ischemic limb pain. In addition, the consequences of overlooking polymyalgia rheumatica as an early manifestation of giant cell arteritis are outlined.
The therapeutic effect of once weekly transcutaneous electrical nerve stimulation in patients with rheumatoid arthritis was compared with placebo in a randomised, double-blind, non-crossover study lasting three weeks. Thirty-two patients with classic or definite rheumatoid arthritis and wrist involvement were evaluated. Transcutaneous electrical nerve stimulation was better than the placebo in relieving pain at rest and while gripping. In addition, grip strength, measured as power and work done, immediately improved following transcutaneous electrical nerve stimulation but returned almost to initial values between assessments. No significant improvement was shown for the placebo group.
A simple pressure dolorimeter for the detection and quantification of joint tenderness is described and evaluated. The pressure dolorimeter was more sensitive than a modified Ritchie Index in measuring degree of joint tenderness and as sensitive in detecting tender joints. The interobserver error of the pressure dolorimeter was low, and in a drug withdrawal study, the pressure dolorimeter was able to detect change in joint tenderness whereas the conventional Ritchie Index was not. These results suggest that the pressure dolorimeter is a simple, reliable and sensitive instrument for measuring joint tenderness in patients with inflammatory joint disease. It is also inexpensive and readily available.
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We report the effects of some common antirheumatic drugs on the production of catabolin from synovium and on its action on cartilage. A method is described to generate reproducible amounts of catabolin from synovial mince. Aspirin, Clozic (ICI 55,897), and gold were without effect on the catabolin system. Penicillamine at high doses enhanced the action of catabolin, while chloroquine inhibited catabolin's effect on cartilage. Prednisolone inhibited the production of catabolin without affecting its action. This inhibition was produced by very low doses of prednisolone (25 ng/ml) and was dose-dependent.
A study of post-mortem examinations performed between 1970 and 1979 at a specialist orthopaedic hospital revealed that the overall mortality rate due to pulmonary embolism was 0.23% and that pulmonary embolism was responsible for 19.1% of hospital deaths. The majority of these fatalities occurred following operation for either fractured proximal femur or total hip replacement. During the decade, 928 patients were operated upon for fractured proximal femur, none received prophylactic anticoagulation therapy and the mortality rate due to pulmonary embolism was 17.7%. However, the yearly mortality rate decreased with time and this change was attributed to earlier operation and early mobilisation. Over the same period, 3016 patients underwent total hip replacement, 20% were anticoagulated prophylactically; the mortality rate due to pulmonary embolism was 0.63%. In those patients who died of pulmonary embolism, post-mortem evidence of deep vein thrombosis was usually found, but no relationship between site of thrombosis and side of operation was observed. Pulmonary embolism was diagnosed in only a few patients although on later consideration at least a third of patients had symptoms suggestive of previous emboli. Possible improvements in diagnosis are discussed and a more rational approach to prophylactic anticoagulation suggested.
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Fifty-two patients with stable rheumatoid arthritis were followed-up for one year after being referred to the Disablement Resettlement Officer for work counselling. The proportion of patients employed following work counselling initially increased from 35% to 67%, falling to 57% after one year. In addition, 44% of patients "off sick" were re-established at work by job modification. Comparison of patients employed or unemployed one year later indicated that successful employment was related more to social and environmental factors than disability ro financial considerations.