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Biomedical subjects

M J Ahern

Publications and source records attributed to M J Ahern.

At least 91 records · Page 5Linked to original sources

Phenotypic and genotypic analysis of mononuclear cells from patients with Felty's syndrome.

Phenotypic and genotypic characteristics of the peripheral blood mononuclear cells in nine patients with Felty's syndrome have been examined. One patient had an increased number and percentage of peripheral blood mononuclear cells with the phenotype CD3+ Leu-7+ CD16+ and showed a clonal rearrangement of the T cell receptor B chain gene. The remaining eight patients all showed a germline configuration of the T cell receptor B chain gene. In two patients an increased proportion of CD3+ Leu-7+ CD16- peripheral blood mononuclear cells (45 (SD 11)% of peripheral blood mononuclear cells) were found, while the remaining six patients had proportions of CD3+ Leu-7+ cells similar to those of patients with uncomplicated rheumatoid arthritis. These data confirm that patients with Felty's syndrome are heterogeneous, with at least three different peripheral blood mononuclear cell phenotypic subsets. One subset is characterised by a clonal expansion of an unusual lymphocyte subpopulation, another by polyclonal expansion, and the third subset has the same proportions of peripheral blood mononuclear cells as patients with uncomplicated rheumatoid arthritis.

Adult↗

Does steroid pulsing influence the efficacy and toxicity of chrysotherapy? A double blind, placebo controlled study.

To test the hypothesis that early steroid pulsing augments the efficacy and decreases the toxicity of chrysotherapy 40 patients with rheumatoid arthritis were studied in a double blind, placebo controlled study. During the first three months of gold treatment group 1 received monthly intravenous methylprednisolone pulsing (steroid group) while group 2 received placebo (placebo group). All patients were assessed clinically and serologically over a 24 week period. Twelve patients were withdrawn before completion of the study and all but one of the remaining 28 patients reported clinical and serological improvements. Two patients in the steroid group were withdrawn owing to gold induced side effects while four were withdrawn in the placebo group. These small numbers were not significantly different. Minor side effects occurred more commonly in the placebo group. The clinical response was clearly better in the steroid group with statistical significance almost being achieved. In an endeavour to obtain a significant conclusion further patients will now be entered into this study.

Aged↗

The Felty syndrome: a case-matched study of clinical manifestations and outcome, serologic features, and immunogenetic associations.

Thirty-two patients with the Felty syndrome, defined by the presence of rheumatoid arthritis, splenomegaly, and neutropenia, have been studied in comparison with 32 patients with rheumatoid arthritis matched for age, sex, and disease duration, and 9 patients with rheumatoid arthritis and idiopathic neutropenia. Patients with the Felty syndrome had severe destructive arthritis, which progressed during follow-up despite little evidence of objective synovitis, and a higher frequency of extra-articular manifestations, including vasculitis. Bacterial infection tended to occur in patients with the lowest neutrophil count but continued to occur in some despite normalization of the WBC. Prognosis was poor and 8 deaths occurred, predominantly from sepsis. Serologic features were prominent. High titers of IgG rheumatoid factor and circulating immune complexes characterized patients with persistent neutropenia. A family history of rheumatoid arthritis was more common in patients with the Felty syndrome. The association with HLA DR4 was very strong; in addition there was an increased frequency of the DQw3 variant, 3b, suggesting that HLA Class II genes in linkage with DR4 may contribute to disease expression.

Adult↗

Impaired delayed type cutaneous hypersensitivity in rheumatoid arthritis reversed by chrysotherapy.

A prospective 24 week study of 31 patients with active rheumatoid arthritis (18 women, 13 men) was undertaken to determine whether weekly intramuscular sodium aurothiomalate (gold) would influence delayed type cutaneous hypersensitivity (DTH) and other indices of cell mediated immunity. DTH to seven recall antigens was measured by Multitest on three occasions during the study. Twenty five patients completed the study. At entry 13 patients (12 female) were anergic, and no significant correlations were found between DTH and other clinical and immunological indices. Women showed a significantly greater depression of DTH than men. At week 24 only three of the patients were anergic with significant increase in mean DTH score being noted particularly to tuberculin, candida, and streptococcus. Improvement in DTH was observed in both gold responders and non-responders. In conclusion, patients with active rheumatoid arthritis show impairment of DTH, which is reversed by chrysotherapy. This effect is most apparent in women and appears to be relatively independent of the clinical response.

Adult↗

Pseudomonas peritonitis associated with continuous ambulatory peritoneal dialysis: a six-year study.

In a population of 214 patients on continuous ambulatory peritoneal dialysis (CAPD), 415 peritoneal infections occurred between 1980 and 1986. Fourteen of these infectious events were caused by Pseudomonas aeruginosa (3.4%). None of those patients with P aeruginosa peritonitis were cured by medical therapy alone. Peritoneal catheter removal was necessary to achieve resolution of the infection. Significant patient morbidity from Pseudomonas infection included loss of peritoneal space for further dialysis and abscess formation. Our data suggests that prompt catheter removal should be seriously considered for chronic ambulatory peritoneal dialysis patients who develop P aeruginosa peritonitis.

Adult↗

The disposition of ketoprofen enantiomers in man.

1. The disposition of ketoprofen enantiomers was studied in 21 patients taking racemic ketoprofen (Orudis SR). 2. In each patient the plasma concentrations of the R- and S-enantiomers were similar at all times over a 24 h dosing interval. The mean (+/- s.e. mean) time-averaged plasma ketoprofen concentrations over the dosage interval were 0.76 (+/- 0.06) mg l-1 for R-ketoprofen and 0.78 (+/- 0.06) mg l-1 for S-ketoprofen. 3. Creatinine clearances for the 21 patients ranged from 6-162 ml min-1. There was no correlation between creatinine clearance and time-averaged plasma concentration for either R- or S-ketoprofen. 4. Approximately 30% of the dose was recovered in urine (unconjugated + glucuronide conjugate) and this was made up of 43% R-ketoprofen and 57% S-ketoprofen. Because of incomplete urine recoveries of ketoprofen it was not possible to determine whether inversion from the R- to the S-enantiomer takes place in man. 5. The data suggest that in terms of total (bound + unbound) ketoprofen, half the concentration value derived by a non-enantiospecific analysis would give a reasonable approximation of the pharmacologically active S-enantiomer concentration in plasma.

Aged↗

Pancytopenia induced by low-dose methotrexate for rheumatoid arthritis.

Four cases of pancytopenia related to low-dose weekly pulse methotrexate therapy for rheumatoid arthritis are described. All patients were aged above 60 years and had renal impairment. In every case marrow recovery followed withdrawal of methotrexate. However, one patient developed pneumonitis and died. Cholangitis, respiratory infection and increase in methotrexate dose were precipitating factors. Pharmacokinetic data indicated prolonged tissue drug exposure in two cases studied; dose-related toxicity was further supported by successful resumption of methotrexate in reduced dosage in two cases. It is possible that methotrexate dose should be modified during intercurrent illness in patients older than 60 years who have renal impairment.

Aged↗

Low molecular weight IgM in juvenile chronic arthritis.

Low molecular weight IgM, the monomeric subunit of pentameric IgM, was clearly detected by immunoblotting and filtration chromatographic techniques in six patients with juvenile chronic arthritis and in trace quantities in a further eight of 24 patients studied. This low molecular weight IgM moiety contributed up to 33% of the total circulating IgM and was strongly associated with raised serum concentrations of IgM and the presence of antinuclear antibodies, extractable antinuclear antibodies, and rheumatoid factor. Immunoblot analysis of positive serum samples showed small quantities of other low molecular weight oligomers of IgM in addition to monomeric IgM. It is postulated that the presence of low molecular weight IgM in the serum of patients with juvenile chronic arthritis reflects a disorder of the intracellular assembly of IgM subunits during a stimulated IgM immune response. The pathogenetic role of low molecular weight IgM remains uncertain.

Antibodies, Antinuclear↗

Effects of chrysotherapy on circulating lymphocyte numbers and subsets.

In a prospective 24 week study of 25 patients with rheumatoid arthritis (RA) weekly intramuscular (IM) sodium aurothiomalate resulted in a small but significant reduction in the circulating lymphocyte count. Analysis of absolute levels of pan T cells, T4 helper cells, T8 suppressor cells, T4/8 ratio, B cells, and major histocompatibility complex (MHC) class II positive cells showed reductions in these subsets, though these changes did not reach significance. At entry there was no association between circulating lymphocyte counts and subsets and clinical and laboratory indices which reflected disease activity, and during the study gold responders could not be differentiated from non-responders with regard to changes in lymphocyte counts and subsets. Thus this study suggests that weekly IM gold leads to a modest reduction in circulating lymphocyte numbers which involves most subsets. This effect appears to be independent of the clinical efficacy of this drug.

Arthritis, Rheumatoid↗

Pulse steroid therapy in rheumatoid arthritis: can equivalent doses of oral prednisolone give similar clinical results to intravenous methylprednisolone?

Pulse methylprednisolone therapy has dramatic effects on clinical and immunological parameters of disease activity in patients with rheumatoid arthritis. Previous studies of this treatment have all used the intravenous route and methylprednisolone succinate. This study addresses the question of whether oral prednisolone in equivalent doses can substitute for intravenous methylprednisolone in pulse therapy in a double blind parallel study. It is shown that oral prednisolone has clinical and immunological effects equivalent to those of intravenous methylprednisolone, making it possible to administer pulse therapy to patients with rheumatoid arthritis as outpatients without the inconvenience and inherent dangers of intravenous administration.

Administration, Oral↗

Two distinct quinidine-induced rheumatic syndromes.

Of seven patients with quinidine-induced polyarthropathy, four had positive antinuclear antibodies and could be considered to have had quinidine-induced lupus erythematosus. The remaining three patients had milder symptoms, which occurred soon after the start of quinidine therapy, and did not have antinuclear antibodies. To confirm the association, the latter three patients were rechallenged with quinidine therapy, which caused recurrence of symptoms within 1 week. Antihistone antibodies, which are characteristic of drug-induced lupus erythematosus associated with procainamide and hydralazine therapy, were detected in all patients with quinidine-induced lupus erythematosus. An unusual characteristic of antihistone antibodies seen in two patients was the presence of high levels of IgG antibodies to histone H1 as well as H2A.H2B and H3.H4 complexes, without antibodies to the individual core histones.

Aged↗

The clinical and immunological effects of pulse methylprednisolone therapy in rheumatoid arthritis. II. Effects on immune and inflammatory indices in peripheral blood.

Marked effects on C reactive protein, circulating immune complexes, rheumatoid factor and immunoglobulin levels were demonstrated in a group of 40 patients with rheumatoid arthritis, who received pulse methylprednisolone therapy, either as sole treatment or in combination with a disease modifying agent. The only patient groups in which these serological changes were maintained were the groups taking disease modifying agents, with the more significant and sustained changes occurring in the group of patients who started a disease modifying agent at the time pulse therapy was begun. No significant effect of pulse therapy on neutrophil or lymphocyte counts or lymphocyte subsets could be demonstrated. Pulse therapy, per se, did not have a significant effect on the results of intradermal delayed hypersensitivity testing in any patient group.

Antigen-Antibody Complex↗

The clinical and immunological effects of pulse methylprednisolone therapy in rheumatoid arthritis. III. Effects on immune and inflammatory indices in synovial fluid.

Pulse methylprednisolone therapy has dramatic effects on cellular traffic and immunological variables of disease activity in both the synovial fluid (SF) and peripheral blood compartments. While these effects persisted at 2 weeks in the SF they had reverted to pretreatment levels in the peripheral blood. Pulse therapy resulted in temporary changes in the number of helper and suppressor cells in peripheral blood with an initial fall followed by a rise in the helper to suppressor ratio. In the SF, pulse therapy produced more gradual and sustained effects on the helper and suppressor subpopulations, resulting in a reduction in the helper to suppressor ratio.

Antigen-Antibody Complex↗

Does colchicine work? The results of the first controlled study in acute gout.

We have performed the first controlled study of colchicine in acute gout, to determine its efficacy and toxicity, and to define the natural history of acute gout. Two-thirds of colchicine-treated patients improved after 48 hours, but only one-third of the patients receiving placebo demonstrated similar improvement. The colchicine-treated patients responded earlier; significant differences from placebo were shown after 18-30 hours. All patients given colchicine developed diarrhea after a median time of 24 hours (mean dose of colchicine 6.7 mg). This side effect occurred before relief of pain in most patients.

Acute Disease↗