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Biomedical subjects

B Bresnihan

Publications and source records attributed to B Bresnihan.

168 records · Page 10Linked to original sources

Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus.

Normal peripheral blood mononuclear cells demonstrated increased DNA synthesis and secretion of newly synthesized protein when suboptimal concentrations of Concanavalin A (Con A) were added to the cultures after 24-h incubation in vitro. Cells stimulated by Con A, 1 mug/ml, after 24-h incubation demonstrated 3.0 times more tritiated thymidine incorporation, and 4.4 times more 14C-amino acid incorporation into newly synthesized secreted protein, than cells stimulated at 0 h (P less than 0.001). The acquisition of increased responsiveness was not abrogated by washing and resuspending the cells in fresh medium. Since the increased responsiveness could be inhibited by the addition to the cultures of small numbers of cells previously activated by Con A it is suggested that the enhanced reactivity acquired in culture represents the loss of a subpopulation of suppressor cells that modulate the T-lymphocyte response. Cells from nine patients with active, untreated systemic lupus erythematosus demonstrated normal responses to optimal concentrations of Con A added at 0 h, but an impaired response to Con A, 1 mug/ml. When these cells were incubated for 24 h, a significant increased response to Con A was not observed. This observation suggests that patients with active SLE lack circulating suppressor cells. When seven SLE patients were again studied after corticosteroid therapy had led to clinical improvement, the response to Con A, 1 mug/ml, added after 24-h incubation was similar to that observed in normal controls, suggesting that suppressor function in SLE returns as disease activity declines.

Adolescent↗

Brain reactivity of lymphocytotoxic antibodies in systemic lupus erythematosus with and without cerebral involvement.

A prospective clinical study of cold-reactive lymphocytotoxic antibodies in systemic lupus erythematosus has been completed. A highly significant association between serum lymphocytotoxicity and the development of cerebral manifestations was observed. While lymphocytotoxic antibodies from patients with cerebral lupus were absorbed by homogenates of human brain, those from patients who at no time had evidence of cerebral disease failed to cross-react with brain. It is suggested that subpopulations of lymphocytotoxic antibodies differ in their brain reactivity, and that one population may be causally related to the development of some of the features of cerebral lupus.

Antibodies↗

Disease-modifying anti-rheumatic drug therapy and structural damage in early rheumatoid arthritis.

The appearance of measurable structural damage in rheumatoid arthritis (RA) is an indicator of disease severity and future disability. Disease-modifying anti-rheumatic drugs (DMARDs) used in combination appear to be more effective than monotherapies at reducing the rate of progressive joint damage during randomized controlled trials. In clinical practice, however, combination DMARD therapy is still largely reserved for patients who have failed to respond to monotherapy. High dose corticosteroid, when given in early disease with combination DMARD therapy, may continue to ameliorate disease severity and progression for years after discontinuation of the high dose. To date, no DMARD combination has totally arrested joint damage in all patients with early RA. Future randomised controlled trials should always include prospective radiographic data as a primary outcome measure.

Adult↗

Anakinra as a new therapeutic option in rheumatoid arthritis: clinical results and perspectives.

Interleukin-1 receptor antagonist (IL-1Ra) is a member of the IL-1 gene family, which blocks IL-1-mediated signal transduction. In rheumatoid arthritis (RA), recombinant human IL-1Ra (anakinra) has been evaluated in 5 randomized, placebo-controlled clinical trials. In the European monotherapy study, 43% of patients receiving 150 mg/day anakinra achieved a 20% response according to the American College of Rheumatology criteria (ACR 20), compared to 27% in the placebo group. In the methotrexate combination therapy study, 42% of the patients receiving 1 mg/kg/day anakinra achieved an ACR20 response, 24% an ACR50 response, and 10% an ACR70 response. In each study, clinically meaningful improvements in the Health Assessment Questionnaire scores were observed. The Economic Resource Survey was employed in the European monotherapy study to evaluate patient and caregiver days of missed work or domestic activity in successive 4-week periods. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose-related. The mean change in the total modified Sharp score of patients who completed treatment with anakinra was significantly less than in the patients who received placebo. Anakinra, a new biologic approach to the treatment of RA, results in significant improvements in the signs and symptoms, has beneficial effects on functional status, and on the rate of progressive structural joint damage.

Antirheumatic Agents↗

Chronic active hepatitis in a patient presenting with clinical and serological evidence of SLE.

A patient with clinical and serological manifestations of systemic lupus erythematosus (SLE) without renal or neurological manifestations was managed conservatively for 4 1/2 years. At this time she developed ascites and abnormal liver function tests, and was found to have severe chronic active hepatitis (CAH) with cirrhosis and portal hypertension. No clinical or biochemical evidence of liver disease was documented over the first 3 1/2 years of her illness, though no tests were performed in the 12 months before diagnosis. This case emphasizes the value of monitoring liver function tests over extended periods in such patients, since appropriate immunosuppressive therapy may benefit CAH, and as in this case, systemic manifestations of CAH may simulate SLE and precede clinical liver disease.

Adult↗