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Biomedical subjects

D L Scott

Publications and source records attributed to D L Scott.

At least 145 records · Page 8Linked to original sources
PubMed1991

Rheumatoid nodules do not predict response to treatment with slow-acting anti-rheumatic drugs.

Rheumatoid nodules have been associated with a poor long-term prognosis. We investigated whether they predict a poor response to treatment with slow-acting anti-rheumatic drugs (SAARDs). Two hundred and twenty-eight patients with rheumatoid arthritis (RA) were treated for six months with a SAARD. Clinical and laboratory assessments of disease activity were made initially and after 6 months' treatment. Patients were divided into two groups according to the presence or absence of nodules at entry. Twenty-one % had nodules before treatment but their response was no different to patients without nodules (79%), both groups showing improvements in all variables. Males were more likely to develop nodules and had a relative risk of 1.7. High titres of rheumatoid factor correlated with nodules and no sero-negative patients had nodules. We conclude that nodules are not predictive of poor response to treatment with a SAARD, despite their presence being associated with a poor long-term prognosis. One possible implication is that SAARDs themselves, despite an early response, may not effect long-term outcome.

Anti-Inflammatory Agents↗
PubMed1991

Joint space in radiologically normal knees.

Joint space loss is a characteristic feature of rheumatoid arthritis and osteoarthritis. It cannot be fully evaluated, however, without knowledge of the normal variability of joint space size. We have measured joint space size using digital image analysis in a population of radiologically normal individuals. Anteroposterior films of the knee were studied from 685 consecutive patients attending Casualty with unexplained knee pain or following trauma, but with no clinical or radiological evidence of arthritis. Results show that in a radiologically normal population, men have larger joint spaces than women and there is a steady decline in joint space size with age. We found no significant difference in joint space size between weight bearing and non-weight bearing women. There was also no difference in patients presenting with pain and those presenting following an injury. Normal joint space size was not related to height, weight or body mass index in a subgroup of 213 patients. We suggest that patients lose joint space with increasing age and eventually reach a 'pain threshold' at which symptoms of osteoarthritis occur. This explains the increase in joint symptoms in those who begin with smaller joint spaces; that is in women and in the elderly.

Adolescent↗
PubMed1991

Septic arthritis complicating hip osteoarthritis.

Four patients with osteoarthritis of the hip, who developed septic arthritis of the affected joint, are reported. The septic arthritis developed insidiously and was diagnosed with difficulty. One patient died, two required subsequent joint excision, and one arthrodesis despite antibiotics. The presence of a recognised predisposing factor to septic arthritis, such as rheumatoid arthritis or a surgically replaced joint, can provide a diagnostic pointer. These cases suggest that osteoarthritis, similarly, is a predisposing factor. It is concluded that joint sepsis should be considered if a patient with osteoarthritis develops new symptoms from a single joint with associated systemic features.

Aged↗
PubMed1991

A clinical comparison of two leading non-steroidal anti-inflammatory drugs.

One hundred patients with rheumatoid arthritis were entered into a randomised, double-blind, cross-over study of naproxen (500 mg b.d.) and diclofenac (50 mg t.i.d.). Each treatment period lasted four weeks with a wash-out period of up to one week on admission and again between periods of active therapy. Compared with baseline, both treatments significantly reduced the duration of morning stiffness, Ritchie Articular Index, daytime and night-time pain and produced a significant improvement in the disease status. Forty-two non-serious presumed side-effects were reported in 21 patients (21%). All were characterised by common everyday signs and symptoms. These largely related to the upper gastrointestinal tract and typical of those commonly reported for non-steroidal anti-inflammatory agents. There were no statistically significant differences between the two treatments for any of the efficacy parameters or in the incidence of side-effects. Patients also expressed an equal preference for the two drugs.

Adult↗
PubMed1991

Variations between rheumatologists in using sulphasalazine.

The increased use of audit and resource management within the health service will focus attention on variations in clinical practice. We have looked at one rheumatological example; the extent rheumatologists vary in their clinical use of a slow-acting anti-inflammatory drug. We studied a single drug - sulphasalazine. In a prospective study sulphasalazine was given to 298 rheumatoid patients at 24 rheumatology centres in South East England. They were followed for 6 months. There were large differences between centres in: the types of patient started on therapy; the numbers of patients remaining on treatment; the responses after 6 months. The difference between some centres was more marked than the expected improvement in clinical and laboratory variables given by sulphasalazine. The use of a slow acting anti-rheumatic drug like sulphasalazine in rheumatoid arthritis is agreed by most rheumatologists in the UK and yet there are wide variations in its use. Our results question the validity of comparing clinical practice and associated costs between centres for even a simple clinical procedure.

Aged↗
PubMed1990

Interfacial catalysis: the mechanism of phospholipase A2.

A chemical description of the action of phospholipase A2 (PLA2) can now be inferred with confidence from three high-resolution x-ray crystal structures. The first is the structure of the PLA2 from the venom of the Chinese cobra (Naja naja atra) in a complex with a phosphonate transition-state analogue. This enzyme is typical of a large, well-studied homologous family of PLA2S. The second is a similar complex with the evolutionarily distant bee-venom PLA2. The third structure is the uninhibited PLA2 from Chinese cobra venom. Despite the different molecular architectures of the cobra and bee-venom PLA2s, the transition-state analogue interacts in a nearly identical way with the catalytic machinery of both enzymes. The disposition of the fatty-acid side chains suggests a common access route of the substrate from its position in the lipid aggregate to its productive interaction with the active site. Comparison of the cobra-venom complex with the uninhibited enzyme indicates that optimal binding and catalysis at the lipid-water interface is due to facilitated substrate diffusion from the interfacial binding surface to the catalytic site rather than an allosteric change in the enzyme's structure. However, a second bound calcium ion changes its position upon the binding of the transition-state analogue, suggesting a mechanism for augmenting the critical electrophile.

Bee Venoms↗
PubMed1990

Crystal structure of cobra-venom phospholipase A2 in a complex with a transition-state analogue.

The crystal structure of a complex between a phosphonate transition-state analogue and the phospholipase A2 (PLA2) from Naja naja atra venom has been solved and refined to a resolution of 2.0 angstroms. The identical stereochemistry of the two complexes that comprise the crystal's asymmetric unit indicates both the manner in which the transition state is stabilized and how the hydrophobic fatty acyl chains of the substrate are accommodated by the enzyme during interfacial catalysis. The critical features that suggest the chemistry of binding and catalysis are the same as those seen in the crystal structure of a similar complex formed with the evolutionarily distant bee-venom PLA2.

Amino Acid Sequence↗
PubMed1990

Crystal structure of bee-venom phospholipase A2 in a complex with a transition-state analogue.

The 2.0 angstroms crystal structure of a complex containing bee-venom phospholipase A2 (PLA2) and a phosphonate transition-state analogue was solved by multiple isomorphous replacement. The electron-density map is sufficiently detailed to visualize the proximal sugars of the enzyme's N-linked carbohydrate and a single molecule of the transition-state analogue bound ot its active center. Although bee-venom PLA2 does not belong to the large homologous Class I/II family that encompasses most other well-studied PLA2s, there is segmental sequence similarity and conservation of many functional substructures. Comparison of the bee-venom enzyme with other phospholipase structures provides compelling evidence for a common catalytic mechanism.

Amino Acid Sequence↗
PubMed1990

Antibodies to cardiolipin and intermediate filaments: a study of autoimmunity in rheumatoid arthritis.

Autoantibodies to cardiolipin and intermediate filaments have both been reported with increased frequency in rheumatoid arthritis. We evaluated the frequency, pathological significance, and diagnostic relevance of these autoantibodies in a series of 124 patients and controls. We studied 81 patients with rheumatoid arthritis, 23 with osteoarthritis, and 20 normals. Antibodies to cardiolipin were measured by an ELISA method and antibodies to intermediate filaments were measured by indirect immunofluorescence using HEp2 cells. Antibodies to cardiolipin were present in 58% of rheumatoid patients and antibodies to intermediate filaments were present in 55% rheumatoid patients. They were both predominantly of IgM class, and were more frequent than in normal or osteoarthritic controls. Correlating levels of both these autoantibodies to clinical and laboratory measures of disease activity such as Ritchie articular index and C-reactive protein level showed that no consistent relationships existed. They were not related to other auto-antibodies such as rheumatoid factors and anti-nuclear antibodies, nor to each other. These results show that antibodies to cardiolipin and intermediate filaments in rheumatoid arthritis are of no diagnostic value, they are not related to disease activity, and have no relationship to other autoimmune disturbances. We suggest that several pathological mechanisms must be involved in the development of autoantibodies in rheumatoid arthritis.

Adult↗
PubMed1990

Monoarthritis of the ankle in diabetes mellitus without neuropathy: a report of three cases.

Diabetes mellitus is associated with several non articular rheumatic conditions and is a cause of Charcot's arthropathy. We report three cases of long-standing insulin-dependent diabetics who developed an inflammatory monoarthritis of the ankle. There was no evidence of a peripheral neuropathy or sepsis. They were all seronegative for rheumatoid factor. In two the synovitis persisted; in the third there was a gradual resolution. This type of inflammatory synovitis has not been previously described in diabetes. It developed after a mean duration of diabetes of 34.3 years (range 18-52 years). We suggest that it may be associated with microvascular changes in diabetes, possibly involving hypoxic reperfusion.

Aged↗
PubMed1990

Diagnostic relevance of fibronectin in cryoprecipitates.

Fibronectin is a known component of plasma cryoprecipitates. It is seen in cryoglobulins from patients with monoclonal gammopathies and also from rheumatoid arthritis, and patients with systemic lupus erythematosus and other connective tissue diseases. We evaluated the clinical relevance of measures of cryoprecipitable fibronectin from the sera of 88 patients with rheumatic diseases and 27 healthy controls. There were 28 patients with rheumatoid arthritis, 19 with systemic vasculitis, 5 with cutaneous vasculitis, and 36 with a systemic connective tissue disorder. We measured total and cryoprecipitable fibronectin and for comparison immunoglobulins G, A, and M and complement C3 and C4. Cryoprecipitable fibronectin was detected in 33% control sera and 42% patient sera. The mean levels were higher in the sera of patients in all diagnostic groups. The highest levels were seen in rheumatoid patients with systemic disease, systemic vasculitis, and connective tissue diseases. The presence of cryoprecipitable fibronectin was related to the clinical activity of systemic vasculitis; none of the 6 patients with clinically inactive vasculitis had detectable fibronectin in their cryoprecipitates; but it was seen in 7 to 13 cases with active vasculitis. There were only weak relationships between cryoprecipitable fibronectin and immunoglobulin and complement levels in cryoprecipitates. We conclude that routinely measuring fibronectin levels in cryoprecipitates is generally of doubtful diagnostic value. However, it appears to be a useful marker of the clinical activity of systemic vasculitis and we recommend its use in the laboratory assessment of vasculitis.

Adult↗
PubMed1990

Synovial fluid fibronectin fragments: no evidence for a mitogenic effect on fibroblasts.

Fragments of bovine plasma fibronectin produced by cathepsin D digestion are reportedly mitogenic for hamster fibroblasts. Rheumatoid arthritis synovial fluid contains many fibronectin fragments, which may contribute to the proliferation of synovial cells. We have therefore investigated the potential of fibronectin fragments to stimulate proliferation of synovial fibroblast-like cells using human material. Affinity-purified human plasma and synovial fluid fibronectin was digested with cathepsin D at pH 3.5 for 0-18 h and proteolysis stopped with pepstatin. A variety of fragments were produced ranging from 50 to 200 kDa when analysed by SDS-PAGE. The proliferative activity of various test preparations was studied using quiescent human skin and synovial fibroblasts. Tests were applied for 24 h to 10(4) cells and DNA synthesis measured by tritiated thymidine incorporation. Both undigested and peptides of fibronectin consistently failed to stimulate DNA synthesis in fibroblasts at all concentrations tested, compared with a phosphate-buffered saline control. This was in marked contrast to human synovial fluid from either rheumatoid arthritis or osteoarthritis patients, which stimulated DNA synthesis in the same system (P less than 0.01). Therefore, our data do not confirm the findings of previous studies in which animal materials were used. We can find no evidence that fibronectin fragments play a role in stimulating synovial proliferation in inflammatory arthritis.

Arthritis, Rheumatoid↗