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Biomedical subjects

M Farr

Publications and source records attributed to M Farr.

At least 37 records · Page 2Linked to original sources
PubMed1989

Efficacy of tests used to monitor rheumatoid arthritis.

The relative efficacy of clinical and laboratory tests used to monitor disease activity in rheumatoid arthritis was determined by consensus analysis in a study of 21 patients treated for 6 months. Erythrocyte sedimentation rate (ESR), which is influenced by the anaemia of chronic disease and by variation in the blood concentration of acute-phase proteins, was the most effective single test. ESR was a better guide to disease severity than measurement of plasma viscosity, serum C-reactive protein, and serum orosomucoid--tests that reflect the blood concentration of acute-phase proteins only. Clinical tests performed poorly unless combined with laboratory data in a numerical index. Consensus analysis can be used to assess the efficacy of clinical and laboratory tests and to identify redundant tests.

Adult↗
PubMed1989

Thymopentin (TP-5) in the treatment of rheumatoid arthritis.

A randomized control trial of TP-5 in rheumatoid arthritis is reported. In a multicentre study, 76 patients were treated with TP-5 50 mg or placebo three times a week for 3 weeks as a slow intravenous injection, and followed for 7 weeks. Clinical parameters such as the Ritchie index and sum score of swollen joints improved significantly on TP-5 compared to placebo. Laboratory parameters did not change but an increased skin test score to common recall antigens was observed. Toxicity was minimal. TP-5 is a potentially useful agent in the treatment of rheumatoid arthritis, although further studies are required to determine the optimal treatment regimen.

Arthritis, Rheumatoid↗
PubMed1989

Sulphasalazine in rheumatoid arthritis: haematological problems and changes in haematological indices associated with therapy.

This prospective study documents the haematological responses in 300 rheumatoid patients (RA) treated with sulphasalazine (SASP) for between 1 and 9 years. It also examines the effect of SASP on the total white cell and platelet counts over 2 years in relation to disease activity in 80 RA patients. Neutropenia occurred in six (2%) (three severe--neutrophil count less than 0.8 X 10(9)/l) after 3 and 12 weeks. The drug was withdrawn in six immediately and in one patient after 21 months when the neutrophil count fell to 0.7 X 10(9)/l. An additional 11 (3.7%) developed mild or transient leucopenia between 2 weeks and 24 months, and eight continued therapy. Thrombocytopenia occurred in one patient at 18 weeks associated with other reactions. Four with Felty's syndrome developed a further fall in the total WBC associated with thrombocytopenia in two. A rise in mean cell volume was common (72%), and macrocytosis (MCV greater than 98 fl) occurred in 27 (9%). Macrocytic anaemia was rare (less than 1%). All haematological problems were reversible. In 80 patients treated with SASP for 2 years there was a significant fall in the median white cell and platelet counts at 3 months associated with improvement in disease activity.

Adolescent↗
PubMed1989

Lymphopenia in rheumatoid arthritis.

Lymphopenia is a recognized but poorly studied feature of rheumatoid arthritis (RA). We set out to establish the prevalence and significance of lymphopenia in RA. A group of 66 RA patients was studied for one year. During this time 10 (15%) had persistent lymphopenia (lymphocyte count less than 1.00 X 10(9)/l) without evidence of Felty's syndrome. A separate study of lymphocyte subsets in 13 lymphopenic RA patients showed marked reduction in T-cell numbers with normal circulating B-cell numbers. The numbers of CD4 and CD8 positive T-cells were equally depressed. Lymphopenia may indicate more severe disease. It was not influenced by changes in disease activity or therapy.

Arthritis, Rheumatoid↗
PubMed1988

Sulphasalazine in rheumatoid arthritis: combination therapy with D-penicillamine or sodium aurothiomalate.

This open study examined the safety of adding a second slow-acting anti-rheumatic drug (SARD) - D-penicillamine or sodium aurothiomalate - to the therapy of 38 rheumatoid patients already established on sulphasalazine. Combined anti-rheumatic therapy given in this way was generally well-tolerated and the incidence of adverse reactions was not increased. During the first year none of the reactions were serious although 9 of the 29 patients (31%) given D-penicillamine and 3 of the 9 patients receiving aurothiomalate developed side-effects requiring withdrawal of the second SARD. Reactions attributed to D-penicillamine were: gastro-intestinal - 6, rashes - 2, and blurring of vision - 1. All 3 reactions occurring with gold were rashes, 2 associated with proteinuria and one with increased liver enzymes. During the second year D-penicillamine was withdrawn in 4 patients due to thrombocytopenia - 2, and rashes - 2. In addition an overall favourable clinical response was achieved in 70% of patients. This approach for combination therapy whereby a second SARD is given to patients already established on a single SARD, appears to minimise the toxicity which is a problem when 2 SARDs are started simultaneously.

Adult↗
PubMed1988

Treatment of psoriatic arthritis with sulphasalazine: a one year open study.

Sulphasalazine (SASP) has recently become established as an effective treatment for active rheumatoid arthritis (RA), but has not previously been used in psoriatic arthritis in which remission-inducing drugs have proved disappointing. In this one year open study, 34 patients with active psoriatic arthritis were treated with sulphasalazine. An overall favourable clinical response was observed in 23 patients (67%). Nine patients (26%) achieved a very good therapeutic response and these either had arthritis associated with spondylitis or the symmetrical type of joint disease. Evaluation at 3, 6 and 12 months showed a significant improvement in inflammatory indices including a reduction in the C-reactive protein level and ESR. The drug was well-tolerated and side-effects were mild. Eight patients (23.5%) stopped the drug because of reactions and one patient with a rash was successfully desensitised. Fifty-three percent continued the drug into the second year. No apparent exacerbation of the psoriasis was observed. These results suggest that sulphasalazine is a safe and potentially effective drug in the treatment of psoriatic arthritis. A double-blind placebo-controlled trial has been set up to determine its true efficacy.

Adult↗
PubMed1988

T-cell functional defects in rheumatoid arthritis: intrinsic or extrinsic?

This study investigated two mechanisms which may underlie abnormal T-cell function [lymphocyte proliferation and interleukin-2 (IL-2) production] in rheumatoid arthritis (RA). These were: (a) a possible lack of the IL-2-producing CD4+2H4+ lymphocytes and (b) the possible inhibitory role of monocytes and neutrophils. Numbers of CD4+2H4+ cells did not differ between normal controls and patients with RA, although IL-2 produced by the peripheral blood mononuclear cells (PBMC) of the same individuals was markedly reduced in the patient group (P less than 0.001). Many rheumatoid peripheral blood mononuclear cell preparations, but very few control, were contaminated with neutrophils (P less than 0.001). This was more marked in patients with active RA than in those with inactive disease (P less than 0.001). Numbers of monocytes were similar in all groups. Monocyte depletion, or addition of indomethacin and/or catalase in PBMC, caused a significantly greater increase of responses in RA patients than in controls. This effect was significantly higher in patients with active disease than in the inactive group. These findings suggest that activated monocytes and neutrophils found in the rheumatoid PBMC preparations exert inhibitory effects mediated, in part, by the production of prostaglandins and reactive oxygen intermediates. Monocyte depletion and partial reconstitution resulted in significant increase of lymphocyte proliferation and IL-2 production in both controls and patients. None of the manipulations performed succeeded in normalizing the deficient rheumatoid T-cell responses. These data support the hypothesis that non-lymphoid cell populations play an important role in the T-cell dysfunction characteristic of RA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Sulfasalazine treatment and lymphocyte function in patients with rheumatoid arthritis.

Sulfasalazine is now an established 2nd line agent in the treatment of rheumatoid arthritis (RA) but its mode of action is unknown. Two separate studies have investigated the possibility that it works in RA by influencing lymphocyte function. After 12 weeks of treatment with sulfasalazine, elevated levels of circulating activated lymphocytes and abnormal ex vivo mitogen response to concanavalin A (Con-A) in 11 patients with RA reverted to normal. An in vitro study investigated the effect of sulfasalazine and its metabolites on mitogen response by healthy and RA peripheral blood mononuclear cells (PBMC). Sulfapyridine (SP) and 5-hydroxy SP suppressed the response of RA PBMC to Con-A. Sulfasalazine, SP and N-acetyl SP suppressed the response of healthy PBMC to pokeweed mitogen. 5-aminosalicylic acid also affected mitogen response and cell viability, which may be relevant to actions of this metabolite within the gut.

Aminosalicylic Acids↗
PubMed1988

Deficient interleukin 2 production in rheumatoid arthritis: association with active disease and systemic complications.

Interleukin 2 (IL-2) production and proliferative responses of peripheral blood mononuclear cells (PBMC) stimulated with three concentrations of PHA were measured in 75 patients with rheumatoid arthritis (RA) and 25 normal controls. All patients were on a standard therapeutic regime, and were assessed for disease activity by clinical and laboratory criteria. Rheumatoid cells showed significantly lower IL-2 production and proliferation than normal PBMC at all PHA doses. These differences were not attributable to different kinetics. Within the rheumatoid population, both IL-2 levels and proliferation were lower in patients with active disease than those with inactive RA. Patients with extra-articular disease showed the most pronounced defects. Proliferative responses showed an inverse correlation with clinical indices of disease activity but not with measures of the acute phase response. Rheumatoid patients had higher proportions of CD4+, TFR+ and Tac+ lymphocytes than controls. Both proliferative responses and IL2- levels showed a positive relationship with the proportion of CD4+ cells, and an inverse relationship with Tac+ lymphocytes. Monocyte depletion and partial reconstitution resulted in an increase of both proliferation and IL-2 production, which was more marked in RA patients, suggesting that depressed IL-2 production may relate in part to monocyte effects. However, this cannot completely explain the magnitude of the defects observed, because normal monocytes did not increase the responses of rheumatoid lymphocytes, neither did rheumatoid monocytes suppress the responses of normal lymphocytes.

Adult↗
PubMed1987

Long term experience of salazopyrin EN in rheumatoid arthritis (RA).

Our studies have shown that Salazopyrin EN is an effective slow-acting anti-rheumatic drug, improving clinical synovitis, depressing the acute phase response, capable of inducing remissions and possibly influencing the progression of joint damage. It is well-tolerated in the long-term with comparatively few serious side effects. Its mechanism of action, however, is still not entirely clear. We have found that the sulphapyridine moiety penetrates the synovial membrane and also that it can modify immune function. While Salazopyrin undoubtedly has an important role in the therapy of rheumatoid arthritis, it probably also has a place in the treatment of seronegative arthropathies and the spondyloarthritides. Furthermore we suggest that it should be used as an anchor drug in combination therapy to attempt to suppress disease activity further and limit joint damage.

Anti-Inflammatory Agents↗
PubMed1986

Ranking of laboratory tests by consensus analysis.

A new analytical technique (consensus analysis) was devised to assess the performance of laboratory tests that are commonly used to monitor the acute and chronic phases of inflammatory disease. On thirty-one tests carried out monthly for 7 months in seventeen patients with rheumatoid arthritis, the consensus analysis procedure ranked plasma viscosity and erythrocyte sedimentation rate in a tie for first place. Measurement of the acute-phase serum protein orosomucoid ranked third. Consensus analysis has the potential to reduce laboratory costs by identifying the most useful tests; it also promises to be helpful in the design of new laboratory tests that are more sensitive and specific.

Adult↗
PubMed1986

Neutropenia in patients with inflammatory arthritis treated with sulphasalazine.

This report describes two patients who developed severe neutropenia one month after starting sulphasalazine (SASP) as treatment for their inflammatory joint disease. Both recovered on stopping the drug. Six further cases (out of a series of 180 patients with inflammatory forms of arthritis receiving SASP therapy) in whom transient leucopenia occurred are also recorded. These patients were able to continue the drug under close supervision. Sulphasalazine is a useful addition to the small number of slow acting antirheumatic drugs (SAARDs) and, despite this complication, is safer than other SAARDs. Careful monitoring of patients is essential, however, particularly in the early stages of treatment, to detect this adverse reversible reaction promptly.

Acute Disease↗
PubMed1986

Side effect profile of 200 patients with inflammatory arthritides treated with sulphasalazine.

The side effect profile of sulphasalazine was documented in 200 patients with inflammatory joint disease treated with the drug for at least 1 year. Fifty-eight percent of patients developed one or more adverse reactions and in 21.5% the drug was withdrawn. A further 28% continued taking the drug at a reduced dose. Five percent of the side effects were judged to be potentially serious. In all patients the reactions subsided on either discontinuation of the drug or reduction of the dose. Gastrointestinal (33%) and central nervous system reactions (19%) were the most common, but all were relatively minor. Neutropenia (2%), thrombocytopenia (1%) and pan-hypogammaglobulinaemia (1%) were potentially the most serious effects. The side effect profile of sulphasalazine in inflammatory joint disease appeared to be similar to that in inflammatory bowel disease, but reactions were more frequent in inflammatory joint disease. Enteric-coated sulphasalazine is a useful addition to the small number of slow acting antirheumatic drugs, and in view of its established efficacy, its level of toxicity was found to be 'acceptable' as long as patients were carefully monitored and regular blood tests were carried out.

Adult↗
PubMed1986

Assessing the progression of joint damage in rheumatoid arthritis.

Joint damage in rheumatoid arthritis can be assessed by plain radiographs of the hands and wrists. There are a number of established methods that give reproducible scores which relate to increasing joint damage by measuring erosions and loss of joint space. Only 3 placebo-controlled trials have shown convincing evidence that gold or cyclophosphamide reduce the rate of progression of joint damage. Most placebo-controlled studies have failed to show a beneficial effect of slow acting antirheumatic drugs on radiological joint damage progression. However, comparative studies or analyses of cohorts of patients taking slow acting antirheumatic drugs show comparable amounts of progression for patients receiving gold and other drugs in this category. In addition, patients who show a clinical response also have less radiological progression after 6 months' therapy. In these circumstances, sulphasalazine produces comparable rates of radiological progression to those produced by gold and penicillamine. There are many problems associated with the use of radiological assessments to determine the progression of rheumatoid arthritis; thus, this method should not be deemed the most important technique by which to measure the success of therapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1985

Plasma and synovial fluid concentrations of sulphasalazine and two of its metabolites in rheumatoid arthritis.

A study was made of plasma and synovial fluid levels of sulphasalazine, one of its dissociation products--sulphapyridine and a metabolite of the latter--acetyl sulphapyridine in patients with rheumatoid arthritis (RA) who were in a steady state on sulphasalazine therapy. Combined sulphapyridine levels were significantly higher than those of sulphasalazine both in plasma and synovial fluid. Synovial fluid levels of both drugs correlated with their plasma levels and were generally slightly lower. Some patients accumulated sulphasalazine and sulphapyridine in the synovial fluid and the mean concentration of sulphasalazine was higher in the fluid than in the plasma. The explanation for this is uncertain. The concentration of combined sulphapyridine in synovial fluid was related to local joint inflammation and more active systemic disease. No consistent association was found between sulphasalazine levels and local or systemic activity. The higher sulphapyridine levels in synovial fluid found in this study suggest the possibility that this moiety could play a more active role in RA than it does in inflammatory bowel disease.

Adult↗
PubMed1985

Fenclofenac-induced selective IgA deficiency in rheumatoid arthritis.

A 35-year-old man with seropositive rheumatoid arthritis developed selective IgA deficiency during treatment with fenclofenac. His arthritis remained quiescent while taking the drug and following its withdrawal his condition relapsed and his serum IgA level returned to normal. This case demonstrates the association of selective IgA deficiency with remission in rheumatoid arthritis induced by fenclofenac as well as aurothiomalate and sulphasalazine. It also shows severe relapse after withdrawal of fenclofenac.

Adult↗