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Biomedical subjects

B M Ansell

Publications and source records attributed to B M Ansell.

At least 73 records · Page 4Linked to original sources

Rheumatoid arthritis, juvenile arthritis, iridocyclitis and the Epstein-Barr virus.

In order to examine the relation of Epstein-Barry virus (EBV) infection to chronic arthritis in children antibodies to EB virus capsid antigen (EBVCA) and rheumatoid arthritis nuclear antigen (RANA) were analysed in sera from 133 patients classified as juvenile rheumatoid arthritis (JRA) or pauciarticular, polyarticular, or systemic juvenile chronic arthritis. Except for an increased frequency in the systemic subgroup, the prevalence of antibodies to EBVCA and titres of anti-RANA antibodies was similar in patients and controls. These data do not support an aetiological role for EBV in chronic arthritis in children, including JRA, and suggest that the mechanisms which may account for the higher titres of anti-RANA antibodies in adult RA do not occur in children.

Adolescent↗

Antinuclear antibodies in the relatives and spouses of patients with systemic sclerosis.

The families of 65 patients with systemic sclerosis were examined clinically and serum samples from each subject were tested for antinuclear antibodies (ANA) by immunofluorescence on HEp2 cells and for precipitating antibodies to soluble cellular antigens including Scl-70. Of 217 blood relatives, 58 (27%) had ANA (42 speckled, 13 nucleolar, one centromere, two homogeneous); 22 (10%) had precipitins, one anti-Scl-70, one anti-PM-Scl, one anti-nRNP, two anti-Ro(SSA), the remainder unidentified). Family members tended to share ANA patterns. Of 38 spouses, nine (24%) had ANA (all speckled) and two showed unidentified precipitins. This compares with an incidence of ANA and precipitins in a control population of 8% and 1% respectively. Antibodies were more common in female than male relatives (particularly in mothers and sisters of probands). Twenty one of the 58 family members with ANA had clinical features of connective tissue disease; the remainder were asymptomatic. The presence of genetic factors influencing autoimmunity is suggested by the incidence of autoantibodies in first degree relatives. Similar observations in spouses, however, indicate that environmental factors may also have a role in these immune abnormalities.

Antibodies, Antinuclear↗

Genetic susceptibility to early onset pauciarticular juvenile chronic arthritis: a study of HLA and complement markers in 158 British patients.

To investigate the genetics of susceptibility to early onset pauciarticular juvenile chronic arthritis (JCA), 158 unrelated ethnic British patients with a mean disease onset of 3.2 years, together with controls, were tested for HLA-A, B, C, and DR antigens. Additionally, 117 patients were also investigated for complement Bf and C4 markers. New observations included an increased frequency of the C4B 2 allotype (p corrected (pc) less than 0.02) and C4A 4,B 2 phenotype (p less than 0.0005). Findings suggested a unique increase of the haplotype HLA-DRw8, Bf*S, C4A*4, C4B*2, HLA-B39, possibly predisposing to more severe disease. Strong positive associations were confirmed with HLA antigens A2 (pc = 2.5 X 10(-8)), DRw8 (pc = 3.5 X 10(-14)), DR5 (pc less than 0.02), DRw52 (pc = 2.8 X 10(-6)) and DR5, w8 phenotype (pc = 3.9 X 10(-6)), and negative associations with DR7 (pc = 5.8 X 10(-7)), DR4 (pc less than 0.002), and DRw53 (pc = 0.004). Antinuclear antibody (ANA) seropositivity correlated with DR5 (p less than 0.02), and in children with chronic iridocyclitis (CIR) Bw62 incidence was raised (p less than 0.03) and B44 reduced (p less than 0.03). HLA-A2 was found in 88% of ANA+, CIR+ patients (p less than 0.01). A significant excess of DR5, w8 heterozygotes was present (relative risk = 41.1) and a lack of corresponding homozygotes. Results are inconsistent with a recessive, dominant, or intermediate mode of inheritance of susceptibility, and favour the existence of at least two DR linked 'disease' genes. Moreover, there may be an interaction in heterozygotes of combinatorial factors associated with DR5 and DRw8 in enhancing susceptibility. Possible immunogenetic mechanisms underlying the observed associations with three antigen classes are discussed. Evidence here suggests a role for the HLA-DQ locus in determining susceptibility to this disease.

Age Factors↗

Total hip replacement in children with juvenile chronic arthritis.

The results of 75 total hip replacements in 42 children with juvenile chronic arthritis are reported after a mean follow-up of 5.4 years. Their ages ranged from 11 to nearly 17 years at operation and many had active disease. Severe pain and marked stiffness of the hips were limiting their independence. At least half of the children were still growing and continued to grow after operation. The patients were carefully selected and gratifying results were obtained, but pre-operative assessment and overall supervision by a rheumatologist are important. Technical difficulties related to the size and maldevelopment of the hip are discussed. There was no infection and the single case of loosening of a femoral component after nine years has been successfully revised.

Adolescent↗

Soft-tissue release of the hips in children with juvenile chronic arthritis.

In juvenile chronic arthritis the hips are commonly affected and this becomes the most important reason for losing independence and mobility: the joint develops a painful flexion contracture with marked loss of movement. Soft-tissue release operations consisting of psoas and adductor tenotomies have proved a safe and effective method of relieving pain and improving function. We report 89 such operations in 52 patients. More extensive soft-tissue release operations or synovectomy of the hips offer no advantage and recovery is often more painful and prolonged.

Adolescent↗

Antibodies to peptidoglycan in juvenile onset ankylosing spondylitis and pauciarticular onset juvenile arthritis associated with chronic iridocyclitis.

Using an indirect enzyme linked immunosorbent assay, antibodies of the IgG class to Streptococcus pyogenes group A peptidoglycan-polysaccharide polymers (PG-GSP) were measured in the sera of 37 patients with juvenile onset ankylosing spondylitis (JAS), 22 with pauciarticular onset juvenile arthritis associated with chronic iridocyclitis and 20 healthy children. Mean antibody activity, measured in arbitrary units, was of 184 U in JAS and 250 U in chronic iridocyclitis (p = NS). The results in both groups differed significantly from those found in healthy children (p less than 0.001 and p less than 0.01, respectively). This suggests either a possible role of bacterial cell wall products in the pathogenesis of these disorders or a state of immune reactivity to PG-GSP in these children.

Antibodies↗

Slow-acting antirheumatic drug use in systemic onset juvenile chronic arthritis.

The records of patients with systemic onset juvenile chronic arthritis were reviewed to study the effects of slow-acting antirheumatic drugs on systemic features of the disease and joint manifestations. Frequency and severity of side effects were also evaluated. The following conclusions resulted from this study. Most children could be treated with an alternate-day corticosteroid regimen. Gold and D-penicillamine treatment was not effective or tolerated during the systemic phase. However, after that phase, joint disease was controlled in 42% and 60% of children, respectively. Chlorambucil treatment was helpful in patients with amyloidosis and in those patients in whom all other drugs had failed. The incidence of side effects of chlorambucil are high, however. Antimalarial drug treatment was well tolerated but ineffective during the systemic phase. It was effective on joint disease alone in 44% of a small number of patients. Azathioprine treatment was well tolerated and effective in 50% of patients.

Adolescent↗

The visualization and characterization of two immunological forms of alpha 2 macroglobulin by immunoelectrophoretic methods.

Two peaks of alpha 2 macroglobulin (alpha 2M) were demonstrated in serum or plasma treated with trypsin using crossed immunoelectro-phoresis (CIEP). Both peaks moved the same distance in the first dimension and separated only when electrophoresed into antibody containing gel. The double peak phenomenon was shown not to be an artefact of the antiserum used and that the sample had to be fresh for both peaks to be visualised. Using the methods of staggered well CIEP and crossed thin layer gel chromatography (CTLGC) both peaks were shown to be of very similar antigenicity and molecular size. The technique of line immunoelectrophoresis (LIEP) demonstrated that the newly described lower peak was the alpha 2M/protease complex. The lowest concentration of alpha 2M/protease complexes that could be detected was 0.03 g/l. The two peaks of alpha 2M do not follow the theory of rocket immunoelectrophoresis (RIEP) and this is discussed.

Chromatography, Thin Layer↗

Azathioprine in 50 rheumatoid arthritic patients intolerant or unresponsive to gold or penicillamine.

This is a retrospective review of 50 rheumatoid patients who had experienced side effects with gold and/or penicillamine and who were treated with azathioprine in routine clinical practice. The mean duration of the disease at commencement of azathioprine was 9.4 years; despite attempts to maintain the dose at 2.5 mg/kg.d because of minor side effects the average daily dose was 1.68 mg/kg.d. By one year, 11 (22%) had discontinued the drug due to side effects; 6 (12%) had not improved in any respect, 20 (40%) had a reduction in the total number of active joints with maintenance of function and in 13 (26%) the total number of active joints had been reduced by more than a half. During year 2 a further 4 discontinued therapy for adverse reactions. No further formal analysis has been performed though 31 patients were still on the drug with a mean duration of therapy for a period of 5 years. Ten of these had less than half their originally affected joints still active; this condition was usually associated with a fall in ESR and rise in haemoglobin but this was not invariable.

Adolescent↗

In vitro stimulation of lymphocytes from patients with rheumatoid arthritis.

Peripheral blood lymphocytes from patients with rheumatoid arthritis (RA) and from normal controls were compared in 20 microliters droplet cultures following stimulation with phytohemagglutinin or concanavalin A. The dynamics of proliferation were significantly changed in RA. Higher numbers of cells in culture were needed to achieve the same response. This may explain the low proliferative responses of lymphocytes from some patients with RA, and apparent changes of in vitro suppressor effects, reported by other authors. Diurnal variations of lymphocytes in RA patients were also studied. No differences in the response to mitogen of lymphocytes taken at 7 AM and 7 PM were found.

Adult↗

Chlorambucil induced chromosome damage in juvenile chronic arthritis.

Sister chromatid exchanges, a sensitive measure of chromosome damage, were counted in peripheral blood lymphocytes from 23 patients with juvenile chronic arthritis receiving long term, low dose chlorambucil treatment. Thirty five patients with juvenile chronic arthritis who had not been treated with cytotoxic drugs served as controls. All of the treated patients have cells with abnormal sister chromatid exchange frequencies. Damage is related to the daily dose and may, in part, be determined by the duration of treatment. Sister chromatid exchanges from nine patients who had received chlorambucil at some time in the past remained high for at least five months after stopping the drug. Long term follow up will determine whether sister chromatid exchange analysis can help predict those most at risk of drug induced malignancies.

Adolescent↗

Radiological findings in seropositive juvenile chronic arthritis (juvenile rheumatoid arthritis) with particular reference to progression.

The radiological effects of peripheral joint disease in 81 patients with seropositive juvenile chronic arthritis were studied retrospectively with an average length of follow up of 11 years. The patients comprised 63 girls and 18 boys with average ages of onset being 10.7 years and 12.1 years respectively. All had developed positive serology within the first year of the disease. X-rays available in 70 of these patients at five years from onset of the disease showed erosive change to be present in all but three. The sites most commonly affected included the carpus, the metacarpal, the metatarsal, and interphalangeal joints, though a third of the patients also showed erosive change in large joints such as hips, knees, or shoulders. Between five and 10 years after disease onset progression of x-ray changes was evident in most patients, with additional joints becoming involved in about one third, though the distribution of joints was similar. After 15 years or more of disease the radiological changes tended to be more stable, but various mechanical difficulties often secondary to poor growth and degenerative change and to primary destructive inflammatory arthritis were evident. No specific drug regimen was found to have been universally effective in suppressing disease, and the frequency of side effects was a significant factor in preventing treatment schedules being maintained for long enough to be effective.

Adolescent↗

Autoantibodies in childhood scleroderma.

The clinical presentation of scleroderma in childhood is even more varied than in adult life. This study of 19 children shows that antinuclear antibodies (ANA) detected on the HEp2 cell substrate are just as common as in the adult disorders. All seven children with diffuse scleroderma or acrosclerosis were ANA positive, as were eight of the 12 with more localised disease. Antinucleolar antibodies were particularly frequent (58% overall), but anticentromere antibody was not observed. Enzyme-linked immunosorbent assays (ELISAs) for antibodies to collagen types I-V, in contrast to adult scleroderma, gave normal results in all childhood cases.

Antibodies, Antinuclear↗