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Biomedical subjects

A L Bell

Publications and source records attributed to A L Bell.

At least 55 records · Page 3Linked to original sources

D-penicillamine induced polymyositis causing complete heart block.

We describe a 63-year-old female patient with rheumatoid arthritis who developed complete heart block and features of polymyositis within a few weeks of starting treatment with D-penicillamine. We believe she is one of only three published patients in whom complete heart block accompanies penicillamine-induced polymyositis. The literature on penicillamine myositis is reviewed with special emphasis on cardiac problems. Patients taking D-penicillamine who develop features suggestive of polymyositis may develop insidious, but potentially life-threatening cardiac involvement and must be carefully monitored.

Arthritis, Rheumatoid↗

Myeloperoxidase deficiency in a patient with rheumatoid arthritis: oxygenation and radical activity by phagocytic cells.

Complete functional deficiency of the phagocytic cell enzyme, myeloperoxidase, is described in a patient with rheumatoid arthritis. Measurement of oxygenation and free radical activity by blood monocytes and polymorphonuclear leucocytes shows gross reduction in myeloperoxidase-dependent chemiluminescence. Implications of these data for theories linking reactive oxygen species to inflammatory tissue damage in rheumatoid arthritis are discussed.

Adult↗

Markers of inflammatory activation: upregulation of complement receptors CR1 and CR3 on synovial fluid neutrophils from patients with inflammatory joint disease.

Expression of the C3 receptors CR1 and CR3 was investigated on neutrophils from paired peripheral blood and synovial fluid samples from 34 patients with inflammatory joint disease (21 patients with rheumatoid arthritis (RA) and 13 patients with other articular diseases (OAD)). Using monoclonal antibodies (anti-CD35, anti-CD11b) and immunofluorescence flow cytometric analyses the percentages of positively labeled cells and the relative fluorescence intensities (as a measure of receptor number) were determined. CR1 and CR3 were found to be present on the majority (> 85%) of circulating neutrophils from normal subjects, RA and OAD patients, and on synovial fluid neutrophils from both patient groups. A strong correlation between neutrophil CR1 and CR3 expression was observed in peripheral blood samples from normal subjects (r = 0.81; P = 0.001), RA (r = 0.79; P = 0.001), and OAD patients (r = 0.83; P = 0.001); in each case the levels of CR3 expression were approximately twice those recorded for CR1. Both CR1 and CR3 expression was upregulated on synovial fluid neutrophils compared with that observed on the corresponding peripheral blood cells. Mean percentage increases observed were: RA patients: CR1, 16.5% (P < 0.001) and CR3, 28.7% (P < 0.001); and OAD patients: CR1, 4.1% and CR3, 26.9% (P = 0.001). Correlation of serum and synovial fluid IL-6, IL-8, and immune complex levels with neutrophil CR1 and CR3 expression failed to demonstrate any significant relationship between the concentrations of these soluble factors and receptor expression. Upregulation of CR1 and CR3 receptors, reflecting neutrophil activation within the inflamed joint, is a consistent finding in patients with inflammatory arthropathies.

Adult↗

A flap augmentation technique for Achilles tendon repair. Postoperative strength and functional outcome.

The efficacy of tendo-Achilles rupture repair by a modified version of Lindholm's technique was studied biomechanically and functionally. The procedure involves secondary reinforcement of a conventionally reapproximated rupture site by means of a backfolded augmentation flap. The flap cross section consisted of approximately one third of the proximal stump. In 18 paired fresh anatomic Achilles tendons, flap augmentation repairs had an average strength of 217.5 N (SD = 44.7), whereas conventional repairs (two interrupted Kessler sutures) failed at an average of 153.9 N (SD = 30.2). In a series of seven augmentation flap patients evaluated clinically and by Cybex dynamometry, an excellent result (by the Percy/Conochie rating) was obtained in six, and a good result in one. Plantar flexion strength in full extension averaged 94% of that of the uninvolved leg. There were no reruptures. These data suggest that flap augmentation may be a useful adjunct to conventional suture repair.

Achilles Tendon↗

Diclofenac inhibits monocyte superoxide production ex vivo in rheumatoid arthritis.

Effects of the nonsteroidal anti-inflammatory drug, diclofenac, on stimulated monocyte superoxide production were assessed directly in vitro and following treatment of patients with rheumatoid arthritis ex vivo. Diclofenac inhibited superoxide generation provoked by serum treated zymosan (STZ) and fluoride anion (F) but not by phorbol myristate acetate (PMA) in vitro. Following patient therapy, inhibition of superoxide production occurred when STZ and PMA, but not F were used as stimuli. No changes were seen in control subjects. The contrasting profiles of inhibition seen in vitro and ex vivo suggest an indirect effect on superoxide production during clinical use of the agent. These data are consistent with the hypothesis that anti-inflammatory drugs may act in rheumatoid arthritis by inhibiting phagocyte superoxide anion production.

Adult↗

Immunoglobulin isotype composition of circulating and intra-articular immune complexes in patients with inflammatory joint disease.

The immunoglobulin (Ig) heavy chain isotype composition of intra-articular and circulating immune complexes (ICs) were determined by a Raji cell flow cytometric assay in paired serum and synovial fluid samples from 15 patients with rheumatoid arthritis (RA) and 15 patients with other articular diseases (osteoarthritis, ankylosing spondylitis, gout, psoriatic arthritis, Reiter's disease). ICs were most prevalent in synovial fluid samples of patients with RA but were infrequently detected in serum and synovial fluid samples from the non-RA patients. ICs in patients with RA were heterogeneous both in the prevalence of Ig subclasses identified and in the distribution of the respective Ig isotypes within the complexes. Furthermore, differences were observed in the Ig isotype composition of ICs in paired serum and synovial fluid samples indicating that circulating ICs may not always arise simply by spill-over from articular sites. The possible mechanisms for IC formation in RA are discussed with reference to four patients who displayed features of extra-articular disease.

Adult↗

Evidence for impaired erythropoietin response to anaemia in rheumatoid disease.

In this study we determined the serum erythropoietin (Epo) levels of 97 anaemic rheumatoid (RD) patients (Hb less than 11 g/dl) of whom 44 had serum ferritin greater than 60 micrograms/l (anaemia of chronic disorders; ACD), 26 had ferritin 20-60 micrograms/l and 27 had ferritin less than 20 micrograms/l. These results were compared with the Epo levels of 36 iron deficient controls (Hb less than 11 g/dl), 33 non-anaemic RD patients and 33 normals. The serum Epo levels of anaemic subjects were significantly higher (P less than 0.05) than those of non-anaemic patients. Despite similar Hb, the Epo results (geometric mean (confidence limits] of the ACD group (38 (32,45) mU/ml) and of RD patients with ferritin of 20-60 micrograms/l (39 (33,46)mU/ml) were significantly lower (P less than 0.05) than those of iron deficient controls (65 (52,80)mU/ml). When the Hb fell to 10 g/dl or less, the serum Epo of 13 RD patients with ferritin less than 20 micrograms/l was 65 (47,89)mU/ml, significantly lower (P less than 0.05) than that of 17 iron deficient controls (104 (78,136)mU/ml). These results justify clinical trials of recombinant human Epo in RD patients with ACD.

Adult↗

Class II major histocompatibility complex antigen expression on unstimulated and gamma-interferon stimulated monocytes from patients with multiple sclerosis, rheumatoid arthritis and normal controls.

HLA-DR, HLA-DQ, and HLA-DP antigen expression was assessed by immunofluorescent flow cytometry on monocytes from 19 patients with active multiple sclerosis (MS), 19 with inactive MS, 7 patients with early active rheumatoid arthritis (RA), and 19 normal controls. Percentage positivity and median channel fluorescence (MCF) were determined after separation of the monocytes (TO) and following 48 h culture with (T48 + IFN) and without (T48) recombinant gamma interferon (rIFN-gamma). The percentage positivity of the cells was normal at TO for all groups of patients for each of the HLA types but statistically significantly increased above normal, on monocytes from patients with inactive MS, after culture with rIFN-gamma. At TO, the MCF values for HLA-DQ, and HLA-DP were statistically significantly increased above normal on monocytes from patients with active MS indicating some pre-programming of the cells in vivo. After culture, when the carry-over from baseline TO values was eliminated, the increment in MCF for HLA-DR, on monocytes from patients with inactive MS, was statistically significantly lower than normal in the non-gamma-IFN cultures but was normal in the presence of rIFN-gamma. Conversely, the increment in MCF for HLA-DP on monocytes from patients with active MS was significantly lower than normal after culture with rIFN-gamma. Therefore, the stimulation required to increase antigen density on cells already expressing antigen may be different to that required to stimulate de novo expression on negative cells. Both systems appear to be abnormal in MS, possibly reflecting differences in disease activity, while only one system appears abnormal in RA.

Adult↗

A possible role for superoxide production in the pathogenesis of contact dermatitis.

Superoxide generation by blood monocytes was examined in patients with irritant, nickel, and chromate hand dermatitis. Phorbol myristate acetate stimulated monocytes generated significantly more superoxide in patients with nickel dermatitis, as did patients with hand eczema generally. No significant stimulation of monocyte superoxide generation occurred with either opsonized zymosan or PMA in the presence of excess superoxide dismutase in any of the groups of hand dermatitis. The results indicate a biochemical stimulation of superoxide which may accentuate the immunological damage in the skin that is observed in nickel and perhaps chromate dermatitis.

Adolescent↗

Monocyte esterase deficiency in malignant neoplasia.

A survey of the incidence of monocyte esterase deficiency in 4000 inpatients (including 808 with malignant neoplastic disease) and 474 normal controls was performed using an automated esterase method. A highly significant excess of patients with malignant disease and the deficiency was evident when compared with normal controls or all other patients. Within the group of patients with malignant disease the demonstrable excess occurred in B chronic lymphocytic leukaemia, non-Hodgkin's and Hodgkin's lymphoma, and carcinoma of the gastrointestinal tract. There was also a significant excess of patients with the deficiency attending the renal unit, both among patients who had had renal transplants and those who had not. A familial incidence of monocyte esterase deficiency was found in 19 (35%) of first degree relatives of those patients in whom family studies were done. It is suggested that the reason for the increased prevalence of the anomaly in these disorders might be that the diminution of esterase activity has a role in their development.

Esterases↗