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G D Champion

Publications and source records attributed to G D Champion.

At least 19 recordsLinked to original sources
PubMed1992

In search of the pathogenesis of refractory cervicobrachial pain syndrome. A deconstruction of the RSI phenomenon.

OBJECTIVE: To discuss the clinical and social phenomenon of refractory cervicobrachial pain, more popularly known as repetitive strain injury (RSI), from the standpoint of medical knowledge and to present the phenomenon as a problem of chronic musculoskeletal pain in which clinical clues suggest a neuropathic pathogenesis. DATA SOURCES: Published articles from both medical and non-medical literature, primarily since 1980, were integrated with our clinical experience and observations. DATA SYNTHESIS: Three sets of formal responses to the issue--medical, psychiatric and sociological--were identified and analysed with respect to the validity of their conclusions, which formed the conventional wisdom. Clinical observation revealed clues to disturbed nociception in a carefully defined set of subjects with chronic cervicobrachial pain. Theoretical pathophysiological correlations of these led to the formulation of an hypothesis. CONCLUSIONS: We doubt that clinical method and diagnostic logic were rigorously applied to the RSI phenomenon, which helped to produce an unresolved controversy with widespread ramifications. Our hypothesis is that there is a central disturbance of nociception in this syndrome, induced by continual afferent barrage from nociceptors in anatomically relevant sites in the neck and upper limbs. Initial and proposed testing of this hypothesis are discussed.

Cumulative Trauma Disorders↗
PubMed1991

Auranofin inhibits the activation pathways of polymorphonuclear leukocytes at multiple sites.

In order to characterize the mechanism by which the anti-rheumatic gold complex auranofin (AF) affects the functions of resting and activated polymorphonuclear leukocytes (PMN) the following studies were performed: (1) The effect of AF on the major processes involved in the respiratory burst of PMN: glucose transport and phosphorylation; hexose monophosphate (HMP) shunt activity in intact cells and in a cell-free system; superoxide production by particulate fractions and intact PMN measured as lucigenin-dependent chemiluminescence. (2) A comparison of the effects of AF added to the PMN before, at the time of, or subsequent to the stimulants [N-formyl-methionyl-leucyl phenylalanine (FMLP), concanavalin A (ConA), calcium ionophore (A23187) and phorbol myristate acetate (PMA)]. (3) The effect of AF on PMN activated by two stimulates (PMA, ConA) added sequentially. AF (0.1-10 microM) caused a dose-dependent inhibition of lucigenin-dependent chemiluminescence regardless of the activator (FMLP, ConA, A23187, PMA) when AF was added before the activator. In contrast, when AF was added to PMN after stimulation, it inhibited only the chemiluminescence of PMN stimulated by PMA. Furthermore, the chemiluminescence was largely unaffected by AF in sequentially activated PMN. The relative sensitivity to AF of the various processes studied indicates that blockade of the activation signal appears to be responsible for inhibition of the respiratory burst of PMN.

Auranofin↗
PubMed1991

The effect of aurothiomalate on the oxidative burst of polymorphonuclear leukocytes varies with the quantity of drug in myocrisin ampoules.

The antirheumatic drug, sodium aurothiomalate (GSTM), is not a well defined substance and chemical changes occur in the heat sterilization of the commercial ampoules (Myocrisin). In a comparison of the pharmacological properties of Myocrisin with freshly prepared solutions of GSTM, their effects on the chemiluminescence of polymorphonuclear leukocytes (PMN) activated by phorbol myristate acetate (PMA) were studied. Chemiluminescence was measured in the presence of GSTM from solid material and from Myocrisin ampoules. Myocrisin from 1 and 5 mg ampoules and GSTM in fresh solutions heated at 95 degrees C for 30 min inhibited chemiluminescence, whereas Myocrisin from the higher strength (10-50 mg) ampoules and GSTM in unheated solutions showed no effect at low concentrations and enhancement of chemiluminescence at higher concentrations. Since the gold complexes present in the different strength Myocrisin ampoules do not have identical biological effects, the use of GSTM in investigational studies should involve consideration of its source.

Capsules↗
PubMed1991

Drug treatment of progressive rheumatoid arthritis.

The drug treatment of progressive rheumatoid arthritis (RA) is discussed with emphasis on second line agents used both singly and in combination. NSAIDS play a supportive role in the management of RA. Low dose prednisolone is acceptably safe and effective in long term use whereas pulsed steroids and intra-articular use is reserved for short term control of disease. Antimalarials are rarely valuable as sole agents in progressive arthritis. The use of sulphasalazine, gold thiomalate, d-penicillamine, auranofin, methotrexate, azathioprine and cyclophosphamide in rheumatoid arthritis and their place in the therapeutic strategy are discussed. The reported use of combination chemotherapy has not shown the expected additive benefits although azathioprine, methotrexate and hydroxychloroquine combination may prove to be better than single agents. Recently cyclosporine and gamma interferon have not been shown to be highly efficacious. Of the new therapies monoclonal antibodies to CD4 and CD5 positive lymphocytes are showing promise of marked efficacy in the short term. Sustained control of synovitis appears to improve the long term outcome but better strategies and better drugs are needed.

Anti-Inflammatory Agents↗
PubMed1990

The activation of gold complexes by cyanide produced by polymorphonuclear leukocytes--I. The effects of aurocyanide on the oxidative burst of polymorphonuclear leukocytes.

It has been suggested that the antiarthritic gold complex, aurothiomalate (Autm), is activated by its conversion to aurocyanide by polymorphonuclear leukocytes (PMN) which generate cyanide from thiocyanate. In an examination of this hypothesis, a study has been conducted on the effects of aurocyanide on the oxidative burst of polymorphonuclear leukocytes (PMN) and monocytes activated by phorbol myristate acetate (PMA). Aurocyanide produced delayed inhibition of the oxidative burst as shown by its effect on both lucigenin and luminol-dependent chemiluminescence and on the production of superoxide. It was a more potent inhibitor of luminol-dependent chemiluminescence than free thiomalate and other by-products of the reaction between Autm and cyanide. Aurocyanide had a biphasic effect on the PMA-stimulated hexose monophosphate shunt of PMN, with enhancement at 0.1 microM and inhibition at 10 and 100 microM. The activity of aurocyanide was also compared with that of auranofin, an orally active gold complex, which inhibits a variety of functions of PMN and monocytes. At low concentrations, auranofin produced delayed inhibition of chemiluminescence in a similar fashion to aurocyanide but at high concentrations was an immediate inhibitor of the oxidative burst.

Auranofin↗
PubMed1990

The gold complexes.

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Arthritis, Rheumatoid↗
PubMed1989

Effects of low dose corticosteroids on bone mass in rheumatoid arthritis: a longitudinal study.

Low dose corticosteroids are effective in suppressing synovitis in rheumatoid arthritis (RA), but there remains concern about their side effects, particularly osteoporosis. To examine the effects of low dose corticosteroids on bone loss in RA bone mineral density (BMD) was measured in the lumbar spine and hip for up to two years in 15 patients treated with these agents (mean dose prednis(ol)one 6.6 mg/day). 15 patients not receiving them, and 15 age matched controls. The initial BMD at both skeletal sites was significantly reduced in both patient groups compared with controls. The mean change in bone density was 0.2, 0.1, and -0.1% a year in the spine and -2.0, -1.9, and -1.0% a year in the hip respectively for the three groups. These rates of bone loss were not significantly different between groups at either site. These findings suggest that low dose corticosteroid treatment in RA is not associated with an increased risk of osteoporosis.

Arthritis, Rheumatoid↗
PubMed1988

Synovial complications of spondylepiphyseal dysplasia of late onset.

We describe 2 patients with a late-onset type of spondylepiphyseal dysplasia who developed multiple synovial complications. The synovial manifestations in the first patient included recurrent episodes of acute arthritis due to calcium pyrophosphate dihydrate crystal deposition and, later, chronic synovitis with radiologically evident chondrocalcinosis. In the second patient, cholesterol crystals in synovial fluid, multiple osteochondromata, and a histologic appearance resembling pigmented villonodular synovitis on synovial biopsy were seen. Osteochondromata were identified in 4 other members of this patient's family. Synovial manifestations in the osteochondrodysplasias may be more common than previously recognized.

Acute Disease↗
PubMed1988

Sex hormone status and osteoporosis in postmenopausal women with rheumatoid arthritis.

Sex hormones have important effects on bone, especially in postmenopausal women. These hormones may be of particular significance in patients with rheumatoid arthritis (RA), who have a high frequency of osteoporosis. To examine this, we measured estrogen and androgen concentrations and bone mineral density (BMD) in 49 postmenopausal women with RA and 49 normal postmenopausal women. Compared with the controls, postmenopausal RA patients had significantly reduced levels of estrone (median 18 pmoles/liter versus 49; P less than 0.001), dehydroepiandosterone sulfate (DHEAS) (median 0.3 mumoles/liter versus 2.0; P less than 0.001), testosterone (median 0.6 nmoles/liter versus 0.95; P less than 0.001), and femoral BMD (mean 0.72 gm/cm2 versus 0.80; P less than 0.002). Prednisolone therapy in 22 patients (mean dosage 8 mg/day) was associated with reductions in estrone and testosterone levels; however, DHEAS and femoral BMD were also decreased in RA patients who were not receiving corticosteroids. Reduced DHEAS levels in postmenopausal women with RA may increase their risk of osteoporosis.

Arthritis, Rheumatoid↗
PubMed1988

Stereoselective disposition of ibuprofen enantiomers in synovial fluid.

The simultaneous disposition of the enantiomers of ibuprofen in synovial fluid and plasma was studied in eight patients with arthritis. Concentrations of the active S-enantiomer in synovial fluid exceeded those of the R-enantiomer at all times in all patients with the ratio of S to R concentrations being 2.1 +/- 0.3 (mean +/- SE). Synovial fluid concentrations fluctuated much less than in plasma and exceeded plasma concentrations from 5.4 +/- 0.3 hours for R-ibuprofen and 5.5 +/- 0.6 hours for S-ibuprofen. Pharmacokinetic analysis suggested that, although the enantiomers diffuse into synovial fluid primarily in the unbound form, there may be significant diffusion of the enantiomers out of synovial fluid in the protein-bound form in some patients. Interpatient differences in the disposition of the enantiomers of ibuprofen in synovial fluid were evident and may contribute to the interindividual variability in response to treatment with ibuprofen.

Female↗
PubMed1988

The oncogenicity of chlorambucil in rheumatoid arthritis.

Chlorambucil is useful in patients with rheumatoid arthritis (RA) refractory to other agents but there is concern about the risk of haematological malignancy with this agent. A retrospective survey was performed to assess the incidence of all types of malignancy in 39 patients treated with chlorambucil (mean daily dose 4.25 mg, mean duration of treatment 25 months). These patients were compared with 30 patients with RA who received contemporaneously, the purine analogues azathioprine or 6-mercaptopurine (mean dose 100 mg, mean duration of treatment 24 months). Eight patients treated with chlorambucil and one patient receiving purine analogues developed cutaneous malignancy (p = 0.03). In the chlorambucil-treated patients these were mostly multiple and recurrent. Three patients treated with chlorambucil developed myeloid leukaemia or a preleukaemic state, whilst no patient treated with purine analogues developed this complication. The use of chlorambucil in RA is associated with an increased risk of cutaneous as well as haematological oncogenesis.

Acute Disease↗
PubMed1988

Interaction of salicylate and corticosteroids in man.

Corticosteroids have been reported to decrease the plasma concentrations of salicylate when salicylates have been administered chronically at high doses. In the present study, two single, oral doses of sodium salicylate, 10 mg kg-1 were administered to six adult subjects with a variety of inflammatory conditions both before and during treatment with daily oral doses of prednisone (12-60 mg). Concomitant prednisone therapy did not increase the whole body clearance of single doses of salicylate in these subjects (0.0275 +/- 0.08 l kg-1 h-1 before prednisone; 0.0247 +/- 0.03 l kg-1 h-1 during prednisone therapy; P greater than 0.05). These results indicate that corticosteroids do not alter the clearance of single doses of salicylate in man.

Adrenal Cortex Hormones↗