PubMed Health⌕ Search

Biomedical subjects

M Farr

Publications and source records attributed to M Farr.

At least 55 records · Page 3Linked to original sources

Raised serum alkaline phosphatase and aspartate transaminase levels in two rheumatoid patients treated with sulphasalazine.

Hepatotoxicity is a rare complication of sulphasalazine therapy in ulcerative colitis. This report describes two rheumatoid patients in whom raised serum levels of liver enzymes occurred soon after starting sulphasalazine treatment for their arthritis. In both cases the serum enzyme levels returned to normal after stopping the drug. Drug-induced hepatotoxicity should be considered in patients with rheumatoid arthritis (RA) who develop raised serum levels of liver enzymes while taking sulphasalazine.

Aged↗

Platelets in the synovial fluid of patients with rheumatoid arthritis.

In a study of synovial fluid from 110 patients with various forms of arthritis, platelets were identified in the synovial fluid of all the 50 rheumatoids, in 18 out of the 25 (72%) with osteoarthritis and in all 35 of those with other forms of inflammatory osteoarthrosis. Identification of platelets by light microscopy was confirmed by electron microscopy. Platelet counts were significantly higher in rheumatoid fluid (mean 14 988/mm3; range 1000-65 000/mm3) compared with fluid from patients with osteoarthrosis (mean 1 592/Mm3; 0-10 000/mm3). In addition, significantly higher platelet counts were found in the synovial fluid (SF) of inflamed joints. There was a positive correlation between the SF platelet count and the total white cell count, polymorph count, hydrogen ion concentration, knee score, acid phosphatase and 5-nucleotidase activity and a negative correlation with the glucose level. All these factors indicate joint activity. Finally, platelet numbers correlated with SF levels of immunoglobulin M, and seropositive patients had significantly higher platelet counts in the SF compared with seronegative patients. Rheumatoid patients with thrombocytosis also had higher SF platelet counts. The close relationship of the SF platelet count to other indices of inflammation supports the concept that platelets may directly contribute to synovial inflammation by a variety of pathways.

Arthritis↗

Lymphocyte sub-populations and NSAIDs. Methodological aspects.

Activated lymphocytes can be enumerated as the less dense lymphocyte population (LDL) on a Ficoll density gradient column. The numbers of LDL are higher in rheumatoid arthritis (RA) but fall with successful second-line therapy; they correlate with active synovitis rather than with extra-articular disease. A cytospin technique has been developed which uses fewer cells than conventional suspension techniques and which allows further characterization of LDL using monoclonal antibodies. This confirms that these cells are relatively T-depleted but enriched in IA bearing cells, which may relate to homing patterns to the RA synovium. Using this technique, RA patients with active synovitis were shown to have more LDL and IA bearing cells, as were the active disease controls, including patients with other autoimmune disease (vasculitis) and with non-immune disease (sepsis). There were no differences between the ratios of T-suppressor to T-helper cells within these patient groups.

Anti-Inflammatory Agents↗

The long term effects of sulphasalazine in the treatment of rheumatoid arthritis and a comparative study with penicillamine.

The long term efficacy and tolerability of sulphasalazine (SASP) in the treatment of 21 patients with active classical or definite rheumatoid arthritis (RA) were examined and compared with the effects of penicillamine in a similarly active group of RA patients. Nineteen of the 21 patients treated with SASP improved during the first 6 months as shown by significant changes in the clinical and laboratory variables. Clinical improvement was maintained for the remainder of the year. Improvement in laboratory variables was maintained at 9 months but showed some deterioration at 1 year. Six patients went into remission by the ARA criteria, and 16 were able to continue the drug at the end of 1 year. In addition SASP had a steroid-sparing effect in 4 of the patients on systemic steroids. No potentially dangerous side effects were encountered by the end of the first year, although 5 patients were withdrawn. Dyspepsia, nausea and abdominal discomfort were the most common side-effects, although rashes (3) and macrocytosis (2) also occurred. Eighteen of the 21 patients treated with penicillamine improved during 9 months, although there was some deterioration at 1 year. Eight patients were withdrawn because of side-effects - thrombocytopenia (5), nephrotic syndrome (1) and proteinuria (2). This study suggests that SASP has a disease modifying action maintained over a year and associated with low toxicity. It is a useful addition to the small number of second-line drugs with a possibly different mode of action.

Adult↗

Septic arthritis and thigh abscess after dilatation and curettage.

A previously fit 57-year old housewife who developed a septic arthritis of the right knee and abscess in the right thigh after dilatation and curettage is described. This is the first report of joint and soft tissue complications occurring together after this procedure. Despite antibiotic therapy which eradicated the joint infection, the abscess required surgical intervention. This illustrates the potential morbidity of septic complications after a minor surgical procedure.

Abscess↗

Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients.

Thiobarbituric acid (TBA)-reactive material is present in serum and knee joint synovial fluid from rheumatoid patients, consistent with lipid peroxidation occurring in vivo. The amount of TBA-reactive material in synovial fluid correlates with the concentration of iron salts present as determined by the bleomycin method, presumably because iron is an important catalyst of radical reactions in vivo. There appear to be significant correlations between the contents of TBA-reactive material and bleomycin-detectable iron in synovial fluid and the activity of rheumatoid arthritis as assessed with a clinical index of local inflammation and with various laboratory parameters.

Arthritis, Rheumatoid↗

Whipple's disease diagnosed at hip arthroplasty.

A patient is reported with a six-year history of seronegative inflammatory arthritis, lymphadenopathy, and a rash. Many investigations, including repeat jejunal and synovial needle biopsies, failed to establish the diagnosis. Eventually right hip destruction led to arthroplasty. Synovial membrane obtained at operation was examined by electron microscopy and organisms were found with the morphological characteristics of those in patients where the diagnosis was firmly established as Whipple's disease. We propose that Whipple's disease should be seriously considered as a rare but distinct and treatable possibility in the differential diagnosis of seronegative inflammatory arthritis.

Adult↗

Ultrastructure of synovial changes in rheumatoid disease and in seronegative inflammatory arthropathies.

Synovial tissue has been examined by electron microscopy from patients suffering from either sero-positive or sero-negative inflammatory arthropathies to allow direct comparison of the ultrastructural changes found in these groups and to confirm and extend observations previously made in a smaller group of sero-negative arthropathies. Both groups have been compared with material from healthy controls. The sero-positive group comprised 13 cases of 'definite' or 'classical' rheumatoid arthritis. The sero-negative group consisted of 9 cases of arthritis secondary to Crohn's disease (3); Reiter's syndrome (2); Whipple's disease (1); Behcet's disease (1); Wegener's granulomatosis (1) and ankylosing spondylitis (1). The control tissue was obtained from 6 non-arthritic subjects undergoing surgery for non-inflammatory conditions. Confirmation was obtained of changes previously reported in subcellular organelles, especially in synovial B cells, in all forms of inflammatory arthritis as compared with controls. Attention is now drawn to other intracellular changes in B cells and intermediate cells which included: a marked increase of intermediate filaments and microfilaments: and proliferation of pinocytotic vesicles and rough endoplasmic reticulum. These changes were often accompanied by the presence, in the immediate environment of these cells, of extracellular microfibrillary masses but little or no accumulation of intermediate filaments. It was confirmed that synovial A cells were reduced in number but showed changes suggestive of increased phagocytic activity and also exhibited proliferation of cytoskeletal elements. Differences in these structural changes between sero-positive and sero-negative arthritis were of degree rather than of kind and no 'specific' or diagnostic differences were observed between the various forms of seronegative athropathies. The possible significance of the structural changes observed is discussed.

Arthritis↗

Ferroxidase and ascorbate oxidase activities of caeruloplasmin in synovial fluid from rheumatoid patients.

1. The protein caeruloplasmin inhibits certain free radical reactions, in part probably due to its ability to oxidize Fe2+ into Fe3+ (ferroxidase activity). Since caeruloplasmin is present in synovial fluid from rheumatoid patients, we investigated its properties in relation to protection of the joint from damage by oxygen radicals produced by activated phagocytes. 2. The ferroxidase and ascorbate oxidase activities of serum from both normal and rheumatoid patients could be accounted for by the caeruloplasmin present, as determined immunologically. More caeruloplasmin is present in the serum of rheumatoid patients than in normal serum. 3. Synovial fluid from rheumatoid patients contains caeruloplasmin protein but its ferroxidase and ascorbate oxidase activities are abnormally low. It is suggested that ferroxidase deficiency contributes to radical damage in the rheumatoid joint.

Arthritis, Rheumatoid↗

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↗

Ultrastructure of the synovial membrane in seronegative inflammatory arthropathies.

The ultrastructure of the synovial membrane has been studied in 6 patients with seronegative inflammatory arthropathies: Reiter's (2), Crohn's (2), Whipple's (1) and Behçet's disease (1). The most striking changes were found in the synovial B cells, many containing abnormally large mitochondria with altered cristae surrounded by fibrillar material. Similar material was present in dilated endoplasmic reticulum which was the probable source of groups of extracellular fibrillar spheroidal bodies. The B cells also contained electron dense granular lysosomes of very variable size which, in common with the abnormal mitochondria, were often associated with bundles of orientated microfilaments and large golgi complexes. Light microscopy of the synovial membrane was consistent with an inflammatory arthritis, as were the high white cell counts in the synovial fluid. Systemic activity in the patients was indicated by raised ESR and C-reactive protein (CRP).

Arthritis↗

Synovial fluid and plasma fibronectin levels in rheumatoid arthritis.

1. Plasma fibronectin levels were similar in 60 healthy subjects and 88 with the rheumatoid arthritis. 2. In 42 patients with rheumatoid arthritis synovial fluid fibronectin levels were significantly higher than plasma levels (P less than 0.001). Intermediate fibronectin levels were found in synovial fluid from six patients with psoriatic arthritis, eight patients with osteoarthritis and seven with seronegative arthritis. 3. Plasma and synovial fluid fibronectin levels were not related to indices of inflammatory activity such as the erythrocyte sedimentation rate, the Ritchie articular index or synovial fluid cell counts. Nor did fibronectin behave as an acute-phase protein. 4. Immunofluorescent studies showed that fibronectin was adsorbed on fibrinous debris in rheumatoid arthritic joints. 5. These findings suggest that there is local production of fibronectin by the synovium and suggest that measurement of fibronectin levels in the synovial fluid may serve as an indicator of the tissue response to rheumatoid arthritis.

Adolescent↗

Some observations and speculations on the factors influencing the concentration of phenylbutazone in synovial fluid.

Simultaneous plasma and synovial fluid samples have been obtained from patients, having reached a steady state on phenylbutazone, as a means of investigating factors influencing drug penetration into synovial fluid. Synovial fluid levels are lower than, but related to, plasma levels and are higher in rheumatoid disease (55-100% plasma levels) than in osteoarthritis (less than 50%). Patients with a more active form of the disease have higher synovial fluid drug concentrations. Results are discussed in the light of present knowledge and areas for further study are proposed.

Albumins↗