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Biomedical subjects

P W Thompson

Publications and source records attributed to P W Thompson.

At least 19 recordsLinked to original sources

Post-translational modifications in the collagen of human osteoporotic femoral head.

No detailed biochemical analysis has been made of the possible compositional changes in the collagen relating to the fragility of osteoporotic bone. We report for the first time significant changes in the compositional properties of the collagen. The major differences were observed in the post-translational modifications, namely, in the hydroxylation of lysine residues and the nature of the stabilizing cross-links of the collagen fibre. The increase in hydroxylation was greater in the head region compared to the neck region of the femoral head, whilst the decrease in the intermediate cross-links was greater in the neck region. Clearly, the collagen is altered in osteoporosis and it is important that these changes are recognised in studies of bone metabolism in osteoporosis since they may play a role in the pathogenesis of the disease.

Adult

Urinary collagen crosslinks reflect the radiographic severity of knee osteoarthritis.

The collagen crosslinks deoxypyridinoline and pyridinoline are indices of mature collagen breakdown and reflect increased bone turnover. Urinary levels were found to be significantly raised in a group of 59 women with knee OA compared to 110 female controls from the general population. Levels of the crosslinks correlated significantly with X-ray grade of all subjects including women from the general population with mild, often asymptomatic, disease. These correlations were not diminished after adjustment for age and weight.

Aged

Juvenile chronic arthritis and Wegener's granulomatosis.

We present a case of Wegener's granulomatosis in a teenage boy with systemic onset juvenile chronic arthritis. We discuss the implication of these two uncommon conditions coexisting in one patient. The recent characterization of the antineutrophil cytoplasmic antibody (ANCA) as a marker of small vessel vasculitis has helped in the differential diagnosis of pulmonary renal syndromes.

Adolescent

Morphological evidence that activated polymorphs circulate in the peripheral blood of patients with rheumatoid arthritis.

Purified peripheral blood polymorphonuclear leucocytes (PMNs) from patients with rheumatoid arthritis (RA) have been found to differ from purified PMNs from normal subjects in ways that are consistent with their prior activation. However, it is currently contentious whether activated PMNs really circulate in patients with RA, or whether they are produced as an in vitro artefact of purification. Recently developed rapid leucocyte fixation and preparation technique showed that the proportion of polarised (activated) PMNs (36.9 (24.7)%, mean (SD); n = 31) was increased relative to that in control subjects (8.1 (5.6)%; n = 12). Serum cytidine deaminase levels, a biochemical marker of PMN lysis, were also increased in patients with RA (11.59 (7.26) U/ml) compared with those in controls (6.82 (3.78) U/ml), but the proportion of polarised PMNs and the levels of cytidine deaminase activity were unrelated to clinical assessments of inflammatory disease activity. Twelve patients who were not receiving drugs or who were receiving only non-steroidal anti-inflammatory drugs (NSAIDs) had more polarised PMNs than 19 patients receiving second line treatment in addition to NSAIDs (patients receiving NSAIDs, 49.6 (25.9)%; patients receiving second line treatment, 27.5 (21.1)%). Fluorescence activated cytometric analysis of CR1 and CR3 expression on PMNs from a randomly selected subgroup of patients with RA showed that the serum level of cytidine deaminase activity was correlated positively with the expression of CR1 (the C3b receptor) on the cell surface and that the proportion of polarised PMNs was positively correlated with the expression of CR3 (or CD11b/CD18), the iC3b receptor that is upregulated on activation. It is suggested that the polarised PMNs which circulate in blood samples from patients with RA represent cells which have been activated but not yet marginated, or activated cells which have marginated but subsequently returned to the circulating pool.

Adult

Immune complexes in ankylosing spondylitis.

Immune complexes have been reported in ankylosing spondylitis (AS) and may implicate infectious agents. Serum samples from 49 patients with AS were assayed for immune complexes by polyethylene glycol precipitation, followed by radial immunodiffusion and pepsinogen binding immunoassay. Both methods showed increases in IgA containing immune complexes, which correlated with serum IgA and with IgA rheumatoid factor concentrations, but did not show increases in other immune complex components. Increased immune complexes were associated with peripheral joint synovitis, but showed no correlation with other clinical or laboratory indices of disease activity. Immune complexes from nine AS serum samples and one AS synovial fluid were electrophoretically separated then probed with anti-Klebsiella pneumoniae, but AS specific antigens were not identified. This study did not suggest a major role for immune complexes in AS without peripheral disease, nor provide serological evidence for the involvement of klebsiella antigens.

Antigen-Antibody Complex

Keratan sulphate in rheumatoid arthritis, osteoarthritis, and inflammatory diseases.

Serum concentrations of antigenic keratan sulphate determined by an enzyme linked immunosorbent assay (ELISA) with a monoclonal antibody were studied in patients with rheumatoid arthritis (RA), osteoarthritis, ankylosing spondylitis, other inflammatory diseases, and a large control group of women without arthritis. Mean keratan sulphate concentrations were low in 117 women with RA compared with 227 female control subjects matched for age drawn from a community survey. There were significant correlations between serum keratan sulphate concentrations in patients with RA and serum C reactive protein and the erythrocyte sedimentation rate. Serum keratan sulphate concentrations were also low in 29 men and women with ankylosing spondylitis and 29 patients with arthritis and high concentrations of C reactive protein. In 98 women undergoing an operation for benign breast disease there were decreases in serum keratan sulphate concentrations after the operation which correlated with doses in serum C reactive protein. No differences were found in keratan sulphate concentrations in 137 women with osteoarthritis compared with controls. Within the group with osteoarthritis there were no differences for the various joint groups and there was no obvious correlation with radiographic severity or progression. These findings suggest serum keratan sulphate is unlikely to be useful as a diagnostic marker in osteoarthritis or RA but indicate a role for inflammation in the regulation of cartilage loss.

Acute-Phase Reaction

Use of a risk factor and dietary calcium questionnaire in predicting bone density and subsequent bone loss at the menopause.

One hundred and thirty six healthy white females within 30 months of their last menstrual period (mean age 52 years) were examined to determine the usefulness of a risk factor questionnaire in predicting bone density and subsequent loss. Bone density was assessed at baseline and at 12 monthly intervals. None of the proposed risk factor variables with the exception of nulliparity correlated with the baseline spinal or femoral bone density. As a predictor of bone loss only drinking alcohol (more than four units/day) was significant. A risk factor score derived from the questionnaire before its administration did not correlate with baseline bone density or subsequent bone loss. In most normal women questioned soon after a natural menopause, an estimate of bone density and subsequent bone loss and hence osteoporotic risk cannot be reliably made using a simple risk factor questionnaire.

Alcohol Drinking

A comparison of disability measured by the Stanford Health Assessment Questionnaire disability scales (HAQ) in male and female rheumatoid outpatients.

Eighty-five consecutive rheumatoid patients (M:F = 22:63) seen during a 10-week period were studied. There were significant differences between the sexes for haemoglobin (means (SD) M = 13.5 (1.2), F = 12.0 (1.6) g/dl, P less than 0.01), presence of nodules (M = 50%, F = 19%, P less than 0.05) and for the HAQ scores (mean (SD) score M = 1.1 (0.9), F = 1.7 (0.9), P = 0.03) but not for age, disease duration, presence of erosions, Larsen score, treatment, pain, early morning stiffness, articular index, ESR, and C-reactive protein. The results suggest that the patients were matched for age, disease activity, severity and duration. The difference in haemoglobin between the sexes is in keeping with a reference population. The data suggest that the impact of RA has a greater effect on the functional status of women.

Arthritis, Rheumatoid

The relationship between sex steroids and bone mineral content in women soon after the menopause.

Prevention of postmenopausal osteoporosis is now possible with current therapy, if initiated soon after the menopause and continued for at least 10 years. Simple ways of detecting those at risk of subsequent osteoporosis are urgently needed. This study investigated the hypothesis that certain serum sex hormones could predict bone mineral content (BMC) as measured by dual photon densitometry, soon after the menopause. The subjects included 136 healthy white females within 30 months of their last menstrual period with a mean age of 52 years. Of the sex hormones, the adrenal androgen dehydroepiandrosterone sulphate (DHEAS) correlated best with spinal BMC, a relationship which was significant using multiple regression (P = 0.02), although the correlation was weak (r = +0.19). A direct physiological role for DHEAS has yet to be found, despite being present in large quantities in serum, although it may act as a marker for other processes. No association was seen between testosterone, sex hormone binding globulin, oestradiol, oestrone and oestrone sulphate and spinal BMC. No significant correlations with any hormones were seen with femoral BMC. The data suggest that serum sex hormones are not useful markers of current bone mineral status soon after the menopause, although further work is needed to explore the relationship with DHEAS.

Absorptiometry, Photon

Characterisation of the size and composition of circulating immune complexes in patients with rheumatoid arthritis.

The size and composition of circulating immune complexes in the sera of patients with rheumatoid arthritis (RA) were studied in relation to different manifestations of the disease. Circulating immune complexes from the sera of 94 patients (50 with extra-articular disease) and 10 matched controls were fractionated by sucrose density gradient ultracentrifugation. The composition, immunoglobulin and rheumatoid factor (RF) concentrations within each of the fractions were determined by a sensitive enzyme linked immunosorbent assay (ELISA). Intermediate size (14S-21S) IgG complexes containing RF activity and 22S IgG-IgM RF complexes were found in the sera of 40 patients with RA, while intermediate size complexes of self associated IgG RF and larger size complexes (greater than 22S) of IgG RF and IgM RF were associated with extra-articular features of RA (50% of extra-articular disease). Complexes containing IgA were found in the sera of many patients with RA, and dimeric IgA RF mainly in patients with extra-articular disease. These results support the view that whereas small size circulating immune complexes are of no primary pathogenic importance in synovitis, large size (greater than 22S) circulating immune complexes may play a role in extra-articular disease in RA. Current understanding of the formation of large complexes provides a biological explanation for their occurrence and effects.

Antigen-Antibody Complex

Comparison of four articular indices for use in clinical trials in rheumatoid arthritis: patient, order and observer variation.

Using a Latin square design, 4 patients were examined by 4 rheumatologists. Joints were scored for tenderness and inflammation. The Ritchie, the index of the American Rheumatism Association (ARA), the Hart modified Ritchie and a simplified Lansbury index were calculated from the raw data. The results suggest that an articular index consisting of a simple count of tender joints (Hart modified Ritchie) or a simple count of tender or swollen joints (ARA index) are the most reproducible with multiple observers. We suggest that these indices would be most appropriate for multicenter clinical trials.

Arthritis, Rheumatoid

Evaluation of a simple method for the measurement of cytidine deaminase in serum and comparison with a reference method.

This study was designed to evaluate a cytidine deaminase (CD) assay modified to allow results to be achieved within one working day. Inter-batch variation for samples of mean (SD) CD activity, 10.2 (1.0) units, 17.5 (1.2) units and 31.7 (1.7) units were, 9.8%, 6.9% and 5.4% respectively (n = 26). The reference range (3.2-13.2 U) was similar in males and females and was independent of age. There was close correlation with a reference method (r = 0.96). The mean difference between methods was 2.7 U and the limits of agreement were -1.7 to 7.1 U. The results indicate that the short assay technique can produce results that are sufficiently accurate and precise to be clinically useful.

Arthritis, Rheumatoid