Biomedical subjects
M M Corkill
Publications and source records attributed to M M Corkill.
The management of rheumatoid arthritis.
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In vivo analysis of disease modifying drug therapy activity in rheumatoid arthritis by sequential immunohistological analysis of synovial membrane interleukin 1 beta.
OBJECTIVE: To assess sequential changes of synovial membrane interleukin 1 beta (IL-1 beta) in patients with rheumatoid arthritis receiving chrysotherapy and glucocorticoids. METHODS: Sequential synovial biopsies taken before and after 2 and 12 weeks of treatment were analyzed by immunohistological techniques. RESULTS: Significant decreases in IL-1 beta staining occurred in biopsies taken after 12 weeks' chrysotherapy, while mononuclear cell numbers were unchanged. Results were similar in patients receiving glucocorticoid and gold, and in those receiving gold alone. CONCLUSION: These data suggest that chrysotherapy reduces IL-1 beta production in vivo, a property that has been shown in vitro, and that this change precedes changes in synovial membrane mononuclear cell numbers.
Immunoassay of platelet-derived growth factor in the plasma of patients with scleroderma.
It has been postulated that platelet-derived growth factor (PDGF) is responsible for the abnormal fibroblast proliferation observed in scleroderma. In one previous study, plasma samples from patients with scleroderma caused increased mitogenesis in cultured fibroblasts, suggesting that the pathogenesis of scleroderma is related to increased plasma PDGF concentrations. To test this hypothesis, we used a sensitive, monoclonal antibody-based ELISA to measure PDGF in the plasma of 12 scleroderma patients. A rigorous sampling protocol prevented false elevations in plasma PDGF levels from ex vivo platelet degranulation: beta-thromboglobulin concentrations were measured in each plasma sample to monitor platelet lysis. Plasma PDGF concentrations in the scleroderma patients were not statistically different from those observed in age- and sex-matched normal controls, and patients with RA. While it is possible that changes in PDGF activity at a local level alter fibroblast function, we cannot conclude that elevated plasma concentrations of PDGF play a role in the pathogenesis of scleroderma.
Intramuscular methylprednisolone is superior to pulse oral methylprednisolone during the induction phase of chrysotherapy.
In a randomized double-blinded placebo-controlled trial, 41 patients with RA starting on i.m. sodium aurothiomalate (SAT) therapy were randomized to receive three doses of either 500 mg methylprednisolone (MP) orally and a placebo injection or 120 mg of i.m. depot methylprednisolone acetate (MPA) and oral placebo tablets at 4-weekly intervals. Disease activity was assessed by visual analogue scale (VAS) of pain, grip strength (GS), tender joint count (JC), and Health Assessment Questionnaire (HAQ). Laboratory assessment was by haemoglobin concentration (Hb) and ESR. A composite index of Disease Activity score (IDA) was constructed using all six measurements. The group receiving i.m. MPA showed greater improvement when compared with the group receiving oral MPA. These changes were statistically significant (P < 0.05) for ESR (weeks 2, 6, 8, 10, 12), VAS (week 4, 6, 8), JC (weeks 2, 4, 6, 8, 10) and HAQ (weeks 2, 8, 10). Statistically significantly (P < 0.05) greater improvement in Hb was seen throughout all time points in favour of the group treated with i.m. MPA. Using the IDA score to summarize the results, patients treated with i.m. MPA had better disease remission from weeks 2-12. In all measures, except Hb, no statistically significant difference between the two groups was seen by 16 weeks. We conclude that 120 mg i.m. depot MPA is more effective at inducing improvement in disease activity than 500 mg of oral MPA in RA patients starting on SAT therapy.
Serial soluble interleukin 2 receptor levels in rheumatoid arthritis: differences in response to glucocorticoid treatment and chrysotherapy.
OBJECTIVE: To analyze the changes in soluble interleukin 2 receptor (sIL-2R) levels following treatment of patients with rheumatoid arthritis (RA). METHODS: Serial measurements of sIL-2R levels were made over 24 weeks in 40 patients with RA, treated with intramuscular (im) gold plus 3 im injections of either 120 mg methylprednisolone acetate or placebo. RESULTS: sIL-2R levels were reduced in the glucocorticoid treated group in contrast to the gold only group, where levels initially increased. At 24 weeks, mean sIL-2R levels did not significantly differ from pretreatment levels in either group, despite improvements in clinical measures. CONCLUSIONS: In our study, sIL-2R levels do not correlate with short term clinical measures of disease activity. Their significance for longer term prognostic use remains to be determined.
Interpretation of therapeutic trials.
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Isolated ACTH deficiency presenting with bilateral frozen shoulder.
We describe a 55-year-old female who presented with a 1-year history of tiredness, depression and painful stiff joints. The most striking clinical abnormality was bilateral frozen shoulders, local corticosteroid treatment of which provided the first diagnostic clue. She was found to have profound diminution of plasma cortisol secondary to an isolated deficiency of ACTH. There was no obvious cause for this. Steroid replacement eradicated her lethargy within 3 months and evidence of frozen shoulders resolved completely.
Gold treatment of rheumatoid arthritis decreases synovial expression of the endothelial leukocyte adhesion receptor ELAM-1.
Leukocyte adhesion receptors on endothelial cells play an important role in the evolution of synovitis. We studied sequential synovial biopsies at Weeks 0, 2 and 12 in 11 patients with rheumatoid arthritis beginning parenteral gold therapy either alone or combined with 120 mg intramuscular methylprednisolone acetate at Weeks 0, 4 and 8 of treatment. Expression of endothelial leukocyte adhesion molecule 1 (ELAM-1) decreased on synovial blood vessels after both 2 and 12 weeks treatment (p less than 0.05), while the overall vascularity of the synovium did not change. Neutrophil numbers within the synovial membrane also decreased although this did not reach statistical significance. In contrast, there was no significant change in numbers or subset distribution of T cells or in Class II MHC expression by synovial lining cells, mononuclear cells or endothelial cells. Our results suggest that one of the early effects of intramuscular gold and glucocorticoid therapy may be a downregulation of the acute inflammatory process associated with the endothelial expression of a neutrophil adhesion receptor and the subsequent recruitment of neutrophils into the joint.
Response to glucocorticoid treatment in rheumatoid arthritis: in vitro cell mediated immune assay predicts in vivo responses.
Variable treatment responses to glucocorticoids occur in patients with rheumatoid arthritis (RA). In renal transplantation and asthma treatment responses correlate with in vitro tests of glucocorticoid immunosuppression. We compared in vitro methylprednisolone suppression of concanavalin A stimulated cellular proliferation with clinical responses to methylprednisolone in patients with RA. Patients found to be glucocorticoid sensitive by in vitro testing had significantly greater improvements in joint score and soluble interleukin 2 receptor (sIL-2R) levels compared to control patients, indicating that individual responsiveness to glucocorticoid exists in RA. Similar in vitro and in vivo changes of sIL-2R levels suggests that they reflect cell mediated immune events in vivo.
Pulse treatment with methylprednisolone in rheumatoid arthritis.
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A controlled trial of sulphasalazine treatment of chronic ankylosing spondylitis: failure to demonstrate a clinical effect.
Sixty-two patients with long established but symptomatic ankylosing spondylitis were treated with sulphasalazine or matching placebo in a randomized double-blind controlled trial for 48 weeks. There were no consistent significant differences between the treatment groups in clinical parameters despite multiple assessments. Equivalent numbers in each group were able to decrease or stop non-steroidal anti-inflammatory drug ingestion during the study period (four active, eight placebo). Side effects were reported more commonly in the sulphasalazine group (27 versus 17, NS), but only 21 patients stopped treatment because of side effects (12 versus 9, NS). Analysis of the subgroup with an initial ESR greater than 20 mm/h failed to show any persisting differences of response between sulphasalazine and placebo. We conclude that sulphasalazine therapy does not have a role in the treatment of chronic ankylosing spondylitis.
Intramuscular depot methylprednisolone induction of chrysotherapy in rheumatoid arthritis: a 24-week randomized controlled trial.
Fifty-nine patients commencing intramuscular sodium aurothiomalate therapy were randomized to receive three doses of 120 mg intramuscular depot methylprednisolone acetate or matching placebo at weeks 0, 4, and 8 in addition to chrysotherapy. The group receiving methylprednisolone had more rapid disease improvement. This advantage persisted for up to 12 weeks, although by 24 weeks both groups exhibited similar benefits due to continued improvement in the group treated with gold alone. Withdrawals secondary to gold-induced side-effects occurred later in the steroid group (median time to withdrawal: 15 weeks steroid; 4.5 weeks placebo, P less than 0.05), and there were fewer withdrawals due to a lack of effect in the steroid group (one steroid versus three placebo, P NS). We conclude that glucocorticoids given as intermittent, intramuscular depot injections have a significant short term benefit which can be maintained by concomitant administration of intramuscular gold.
Melioidosis: a new disease to New Zealand.
The first case of melioidosis diagnosed in New Zealand is described. The patient presented with an abscess overlying the liver, which resolved on oral cotrimoxazole therapy, without the need for surgical drainage.
Physician variables in the treatment of myocardial infarction in a single metropolitan hospital.
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