Biomedical subjects
J P Edmonds
Publications and source records attributed to J P Edmonds.
Aortitis with dissection complicating systemic lupus erythematosus.
A 31 yr old female under treatment for systemic lupus erythematosus complained of episodes of atypical chest pain radiating to the back. Subsequently she suddenly collapsed and died. Post mortem revealed a well-defined, localized area of non-giant cell aortitis extending from the supra-aortic ridge of the aortic valve to the ligamentum arteriosum. Active arteritis with fibrinoid necrosis and obliterative endarteritis of vasa vasorum had resulted in multiple infarcts of differing ages with associated inflammation and disruption of the aortic wall, culminating in aortic dissection and cardiac tamponade.
World Health Organization and International League of Associations for Rheumatology core endpoints for symptom modifying antirheumatic drugs in rheumatoid arthritis clinical trials.
The WHO/ILAR core set of endpoints for rheumatoid arthritis clinical trials signifies progress in a continuing worldwide effort. This core set includes the following measures: pain, patient global assessment, physical disability, swollen joints, tender joints, acute phase reactants, and physician global assessment; in studies of one or more years' duration, radiographs of joints should be performed.
Antirheumatic drugs: a proposed new classification.
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New classification of antirheumatic drugs. The evolution of a concept.
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Classification of antirheumatic drugs. A new proposal.
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Use of a molecularly cloned human SS.B antigen to detect anti-SS.B antibodies.
The aim of this study was to examine the utility of diagnostic assays based on recombinant SS.B/La (rSS.B). Using this antigen, we have developed an ELISA and an immunoblot and compared these recombinant antigen-based assays with traditional thymus extract-based counterimmunoelectrophoresis (CIEP). Using the recombinant ELISA, the incidence of anti-SS.B in 184 normal blood donors was 2.2% (four sera). These four sera were all low titre, i.e., 3-5 SD above the mean. Of 38 sera positive for anti-SS.B by CIEP, 37 were positive in both recombinant assays (97.4% concordance). Anti-SS.B titre in CIEP correlated strongly with results of the rSS.B-based ELISA, but the ELISA was 3,000-fold more sensitive. In an analysis of 152 autoimmune sera containing anti-DNA, anti-RNP, anti-centromere, anti-SS.A/Ro or anti-cardiolipin, all of which were negative for anti-SS.B/La by CIEP, the recombinant assays detected 17 new anti-SS.B positives. These positive results were found only in sera which had previously been characterised by CIEP as anti-SS.A/Ro positive. Anti-SS.B/La antibodies detected by recombinant SS.B assays were found to be highly predictive of primary Sjögren's syndrome. Our results show that rSS.B can have an important role in the design of sensitive and specific assays for anti-SS.B. The diagnostic significance of anti-SS.B/La as a guide to primary Sjögren's syndrome is not diminished by the increased sensitivity of recombinant SS.B assays.
Cross-reacting bacterial determinants in ankylosing spondylitis.
The importance of the association between the human histocompatibility antigen human leukocyte antigen-B27 and ankylosing spondylitis is undisputed, but its biologic significance remains unresolved. We have demonstrated specific cross reactivity between a range of enteric bacteria and a specific determinant found only on the surfaces of cells from human leukocyte antigen-B27-positive persons with ankylosing spondylitis. We have proposed that the genetic element coding for this cross-reactive determinant is mobile and that its acquisition by B27-positive cells in vivo represents an important step in the eventual development of ankylosing spondylitis.
Dose response studies and longterm evaluation of auranofin in rheumatoid arthritis.
Fifty-eight patients with rheumatoid arthritis (RA) entered a double blind trial of auranofin (AF) designed to assess dose response relationships and longterm outcome. Multivariate analysis of repeated measures with trend analysis and discriminant function analysis of standard measures of RA activity were applied to a randomized double blind trial of AF at daily doses of 4, 6 and 8 mg over 6 months. Improvement occurred in each group. There was a highly significant (p less than 0.001) linear trend in the 6 mg group, 73% of whom showed linear improvement. A significant correlation (p less than 0.05) was found between response of individual patients and AF dose (mg/kg/day), but there was no significant correlation between dosage and mean steady state serum gold concentration. No significant correlation was seen between outcome and pretreatment demographic and disease variables. In a subsequent 6 month phase of dosage adjustment, aiming for optimal dosage, no advantage resulted from increasing the dose above 6 mg/day. Patients apparently benefiting from treatment continued an open long-term trial of AF. By 45 months, 33.5% had stopped treatment due to lack of efficacy and 14.5% due to toxicity, mainly rash and diarrhea.
HLA-B27, molecular mimicry, and ankylosing spondylitis: popular misconceptions.
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Cytotoxic T lymphocytes against disease-associated determinant(s) in ankylosing spondylitis.
Cytotoxic T lymphocytes, induced by stimulating the PBMC of an HLA-B27+ normal individual (B27+, AS-) with the PBMC of an HLA-identical sibling suffering from ankylosing spondylitis (AS) (B27+, AS+), specifically lyse B27+, AS+ PBMC but not PBMC from HLA-27+ or B27-, AS- normal controls, or from HLA-B27- AS patients (B27-,AS+). CTL of similar specificity can also be raised by immunizing in vitro B27+,AS- cells with autologous cells modified by cross-reactive bacterial antigens. These results suggest that CTL can recognize certain bacterial antigens in association with HLA-B27 and that this interaction may lead to an inflammatory episode during the initial stages of the disease.
Rabbit antisera to cross-reactive organisms--where's the problem.
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HLA-B27 associated cross-reactive marker on the cells of New Zealand patients with ankylosing spondylitis.
We have previously shown that antibodies raised in rabbits to certain enteric bacteria will specifically lyse, in a 51Cr release assay, the peripheral blood lymphocytes (PBL) of 80% of HLA-B27 positive patients with ankylosing spondylitis (B27+ AS+) but not the PBL of HLA-B27 positive normal controls (B27+ AS-). Other laboratories have been unable to reproduce these findings. This study was designed to ascertain whether this lack of reproducibility was due to a peculiarity of our B27+ AS+ patients or to technical difficulties in the complement mediated 51Cr release assay. We have shown in this blind study that the PBL of 16 out of 18 B27+ AS+ patients from a New Zealand population were lysed by our antisera but none of the PBL of 20 B27+ AS- normal controls were lysed. The phenomenon of 'cross reactivity' between certain enteric bacteria and B27+ AS+ PBL is not confined to the Sydney AS population.
Significance of non-pathogenic cross reactive bowel flora in patients with ankylosing spondylitis.
We have previously shown that antisera raised in rabbits to certain enteric cross reactive strains of bacteria are capable of specifically lysing the peripheral blood lymphocytes of HLA-B27 positive patients with ankylosing spondylitis (B27+ AS+). We now report that bacteria with cross reactive antigenic determinants are found in the bowel flora of all of 52 B27+ AS+ patients but in only one of 50 HLA-B27 positive normal controls (B27+ AS-). These organisms are functionally similar to the cross reactive enteric bacteria originally reported. They are not confined to a particular genus or species and their cross reactive serological nature appears to be a property shared by all enteric organisms isolated from B27+ AS+ patients. Organisms with these properties have been shown to persist in the bowel flora of 14 B27+ AS+ patients followed up for more than one year.
The immunopathology of ankylosing spondylitis--a review.
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Gold-induced bone marrow aplasia: successful treatment with antithymocyte globulin.
A patient receiving gold treatment for rheumatoid arthritis developed sudden severe pancytopenia secondary to bone marrow aplasia. She required extensive hematological support but was unsuitable for bone marrow transplantation. Although early use of large doses of a chelating agent did not change the hematological parameters, subsequent use of antithymocyte globulin has been associated with substantial hematological improvement.
The enigma of the Klebsiella connection and ankylosing spondylitis: a commentary.
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Persistence of HLA-B27 cross-reactive bacteria in bowel flora of patients with ankylosing spondylitis.
Previous studies have shown that antisera raised in rabbits to certain enteric bacteria (cross-reactive bacteria) are capable of specifically lysing in a 51chromium-release lymphocytotoxicity test the lymphocytes of HLA-B27-positive (B27+) patients with ankylosing spondylitis (AS). This study investigated the clinical relevance of this finding by ascertaining whether Escherichia coli isolated from the rectal swabs of 20 B27+ AS patients (B27+ AS+) and 46 controls (35 B27- AS- and 11 B27+ AS-) were able to absorb the lymphocytotoxic activity of these antisera. All isolates from B27+ AS+ patients and one from a B27- AS- individual were capable of removing this activity. These organisms persisted in the bowel flora of five selected patients for at least 9 months. Cross-reactive bacteria were also found in a range of gram-positive organisms, including streptococcal, staphylococcal, and clostridial species. The relevance of these findings is discussed in terms of a pathogenetic concept relating the persistence of cross-reactive bacteria in the bowel flora of B27+ individuals to an early event in the development of AS.