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Biomedical subjects

D L Scott

Publications and source records attributed to D L Scott.

At least 235 records · Page 13Linked to original sources

Cancer morbidity in rheumatoid arthritis.

A consecutive series of 489 patients with rheumatoid arthritis seen at the centre was studied to determine their cancer morbidity. Overall the 36 cancers diagnosed in the series between 1964 and 1981 were not significantly in excess of the expected number, but there was a highly significant excess of tumours of the reticuloendothelial system. The excess was mainly due to 6 observed cases of lymphoma. We conclude that there is a highly significant association between rheumatoid arthritis and the subsequent development of lymphoproliferative malignancy in this series.

Adult↗

Lymphoproliferative malignancy in rheumatoid arthritis: a study of 20 cases.

A series of 20 patients with definite or classical rheumatoid arthritis who subsequently developed a lymphoproliferative malignancy are described. The mean time between the onset of the 2 diseases was 13.2 years. A wide range of types of non-Hodgkin's lymphoma and Hodgkin's disease were found; there were no unusual histological features in the lymphomas. Although many of the patients had had gold, penicillamine, and other second-line drugs, none of them had received cytotoxic drugs, and there was no evidence that therapy was a cause of their malignancies. The likely cause of the association is a predisposition to both diseases.

Adult↗

Laminin and vascular proliferation in rheumatoid arthritis.

Laminin is a high molecular weight basement membrane structural glycoprotein. In rheumatoid arthritis and other arthropathies immunoreactive laminin was prominent in synovial blood vessel basement membranes and acted as a marker for them. It codistributed with collagen type IV. Immunohistological reactivity to laminin showed extensive vascular proliferation in rheumatoid arthritis together with basement membrane reduplication, which was confirmed ultrastructurally. Parallel histological studies showed vascular proliferation was predominantly in the subintimal rheumatoid synovium, where it was related to connective tissue proliferation but not to the inflammatory cell infiltrate. Vascular proliferation was also seen in relation to connective tissue changes in biopsies from cases of haemophilic arthritis, osteoarthritis, and meniscal tears. We suggest connective tissue activation is non-specific reaction associated with vascular proliferation. This involves laminin and other structural proteins. It occurs in rheumatoid arthritis and other arthropathies but is distinct from inflammatory cell infiltration.

Adolescent↗

Morphometric effect of prostaglandin E1 and F2 alpha on lactating bovine mammary tissue in vitro.

Mammary explants from six lactating cows were incubated for .17, 4, 8, and 12 h in medium containing prostaglandin E1 or prostaglandin F2 alpha tromethamine salt at 0, 1, 10, or 50 micrograms/ml to determine if prostaglandins alter tissue structure. Explants were fixed, dehydrated, embedded in plastic resins, and sectioned at .5 to 1.0 mu. Tissue area was partitioned by light microscopy into normal, damaged, or debris epithelial; normal or debris lumenal; or stromal areas. All tissue samples exhibited signs of deterioration as incubation progressed. Prostaglandin E1 treatment maintained more secretory epithelium and resulted in less epithelial debris and lumenal debris than controls. Prostaglandin F2 alpha-treated tissue had less epithelial debris and normal lumenal area than tissue receiving no prostaglandin during the limited incubation. The three concentrations of prostaglandins studied did not identify optimal prostaglandins for mammary tissue incubated but indicated concentrations below 1 microgram prostaglandin E1 or F2 alpha/ml should be studied. The response of mammary tissue to prostaglandin was affected by donor milk production. Increases of normal epithelial area were correlated with decreases of damaged and debris areas. Prostaglandins E1 and F2 alpha appeared to be beneficial to healthy mammary tissue incubated under limited conditions.

Alprostadil↗

An experimental model for the study of the opsonic activity of fibronectin in the clearance of intravascular complexes.

An experimental model is described which provides direct evidence of endocytosis of complexes of a charged colloid (dextran sulphate or DS) and of plasma fibronectin (FN) by reticulo-endothelial (RE) cells. This supports previous suggestions that plasma FN acts as a non-immunologically mediated opsonin which effects the clearance of various kinds of circulating colloids and particles by RE cells. DS of molecular weight 500 000 forms FN-containing complexes in rat plasma in vitro and lowers plasma FN levels acutely and in a dose-related fashion when given parenterally to rats. The plasma changes are accompanied by deposition of DS (shown histochemically as metachromatic material) and of FN (shown by specific immunofluorescence) in an identical distribution within RE cells in rat liver and spleen. The protein and polysaccharide components of the complex are disposed of by RE cells at markedly different rates. The model thus also offers a means of studying the dynamics of catabolism of plasma FN by this 'scavenger' pathway. Possible further extensions of the model for other purposes are also discussed.

Animals↗

A model of persistent antigen-induced chronic inflammation in the rat air pouch.

Continuing antigen-induced inflammation was established in a subcutaneous air pouch in rats by recurrent local challenge. The animals were sensitized using bovine serum albumin in Freund's complete adjuvant and were challenged 14 days later by injection of the antigen in a solution containing sodium carboxymethylcellulose into the air pouch to produce allergic inflammation. A single antigenic challenge induced acute inflammation with a predominantly polymorph infiltration in the first 48 h. Later samples showed a low-grade mononuclear response which persisted for 4-5 days. Repeated challenge produced chronic inflammation with an accentuated mononuclear response. Connective tissue activation involving fibronectin and collagen was seen as the inflammation progressed, and this was associated with production of ferritin by mononuclear cells. Discontinuation of challenge injections resulted in resolution of the granuloma. We suggest this model can be used to investigate the mechanisms involved in chronic inflammatory diseases with an immunological component and to evaluate the effects of therapeutic intervention upon chronic allergic inflammation.

Animals↗

Failure of R1 type anti-reticulin antibody to react with fibronectin, collagen type III or the non-collagenous reticulin component (NCRC).

The precise specificity of the R1 anti-reticulin antibody (ARA) associated with untreated gluten sensitive enteropathy (GSE) is unknown. Collagen type III, fibronectin and the non-collagenous reticulin component (NCRC) of Pras & Glynn (1973) co-distribute in tissues in a manner consistent with their being components of reticulin. We therefore used purified preparations of these connective tissue components in studies of the specificity of the ARA. Our results show that the ARA found in GSE does not react with collagen type III, fibronectin or NCRC.

Antibodies↗

The role of fibronectin in the pathogenesis of antigen-induced arthritis in the rabbit.

Fibronectin (FN), a high molecular weight glycoprotein, is present in plasma and is a normal structural component of the synovium in the rabbit, as it is in man. FN is also involved in the sequence of changes seen in synovium in experimental antigen-induced arthritis. Its widespread distribution in inflamed synovia in the initial acute phase of induced arthritis probably merely reflects the presence of FN of plasma origin in serous exudates. In established experimental arthritis, FN co-distributes with fibrin, while in synovia undergoing organisation, FN is present intracellularly in several types of mesenchymal cells (suggesting local synthesis) and is deposited on immature collagen fibrils. However, it is no longer present when mature collagen is formed. The persistence of FN, along with fibrin, in inflamed joints, and its involvement in fibrosis, suggest that it may play a significant part in determining the chronicity of this form of experimental arthritis.

Animals↗

The assessment of radiological changes in the hands and wrists in rheumatoid arthritis.

Two methods of assessing changes in hand and wrist radiographs, the Larsen Index and Amos Index, were compared and contrasted in 48 patients with rheumatoid arthritis (RA). X-rays were taken before and after 1 year of treatment with remission-inducing drugs and scored independently by three observers using both methods. Single readings of radiographs using the Larsen Index were highly reproducible (intra- and inter-observer correlations greater than 0.90 on all occasions), but reproducibility fell when changes were determined from paired films (intra- and inter-observer correlations 0.47-0.82). Variability was greatest in the proximal interphalangeal and wrist joints. The Amos Index, which assesses erosive progression and not the appearance of single films, was more reproducible (intra- and inter-observer correlations 0.72-0.94); it would therefore be better able to detect small changes in groups of patients. The scoring systems were significantly correlated (r = 0.63; P less than 0.001), and with both different observers scored the films at the same "level'. The Amos Index is simple, reproducible, and does not require standard films. It is the assessment of choice.

Adult↗

The use of 'alternative treatments' by patients with rheumatoid arthritis.

In a study of 199 patients with rheumatoid arthritis, 68% were found to have tried 'alternative treatments'. Some treatments (acupuncture and faith healing) gave subjective benefit in nearly half those who tried them and were considered to be better than others (such as copper bracelets). No adverse reactions were reported. 'Alternative treatments' play an important role as self prescribed therapy in rheumatoid arthritis and their use should not be ignored nor underestimated.

Acupuncture Therapy↗

Nitrogen mustard in severe rheumatoid arthritis.

The value of intravenous bolus therapy was investigated in patients with severe active rheumatoid arthritis. Nitrogen mustard was given in 3 intravenous bolus injections (0.1 mg/kg body weight) over 3-5 weeks. In a controlled study of 11 patients the actively treated ones (7 cases) showed greater improvement in all the clinical and laboratory variables measured than did the controls (4 cases). A prospective evaluation of this treatment in 22 patients over 6-18 months showed it had a persistent effect and was associated with clinically significant improvements in the assessments of disease activity. We consider bolus therapy with intravenous nitrogen mustard to be of value, but its use should be restricted to patients with severe rheumatoid arthritis during hospital admission, and it should be combined with other therapy.

Adult↗

Eosinophilia in D-penicillamine therapy.

Cross-sectional and longitudinal studies have been carried out to determine the incidence and clinical significance of eosinophilia in patients taking penicillamine for rheumatoid arthritis. In a cross-sectional study of 204 patients eosinophilia was found with equal frequency during treatment with penicillamine, gold, and nonsteroidal anti-inflammatory drugs. A longitudinal study of 89 patients treated with penicillamine showed no consistent relationship between eosinophilia and adverse reactions to the drug. It is concluded that routine monitoring of eosinophil counts is unlikely to be of value in the management of patients taking penicillamine.

Anti-Inflammatory Agents↗

Musculoskeletal disorders in patients with hyperlipidaemia.

We have assessed the nature and significance of musculoskeletal disorders in 166 patients with the commonly encountered forms of hyperlipidaemia attending a lipid clinic. The incidence of musculoskeletal disorders was determined by questionnaire to the patients, inquiries to general practitioners, and a review of hospital records. To ensure the sensitivity of these methods a series of negatively responding cases were seen and examined; none had identifiable musculoskeletal disease. Eight males with type IV hyperlipidaemia had recurrent acute attacks of gout. The only other musculoskeletal disorder possibly attributable to an association with hyperlipidaemia was a transient polyarthritis in 3 patients. This was inflammatory, recurrent, but nondeforming, and involved the small joints of the hand. It did not require any specific therapy or lead to disability. We suggest that, while we have confirmed the association of type IV hyperlipidaemia and gout, there is little evidence for clinically significant arthritis being associated with other commonly presenting forms of hyperlipidaemia, although we accept that the rarely met homozygous familial hypercholesterolaemia may also be complicated by a crystal arthropathy due to the presence of crystalline cholesterol in joints.

Arthritis↗

Thrombocytosis of active rheumatoid disease.

Two cross-sectional and one longitudinal study of patients with rheumatoid arthritis showed that platelet number correlated with both clinical and laboratory parameters of disease activity, including erythrocyte sedimentation rate, zeta sedimentation ratio, viscosity of plasma and blood, white cell count, liver enzymes, rheumatoid factor, and several acute-phase proteins. There was also an inverse relationship between platelet number and the haemoglobin and serum albumin levels. III Indium-labelled platelet survival was reduced in 4 patients with active rheumatoid arthritis despite a raised platelet count, with labelled platelets being localised to inflamed joints in the 2 patients studied. Platelet aggregation was normal. We suggest that the raised platelet count of active rheumatoid arthritis may be a useful index of disease activity and may represent a bone marrow stress (syndrome) response to shortened platelet survival, with platelet sequestration occurring in areas of synovial inflammation.

Arthritis, Rheumatoid↗