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Biomedical subjects

P A Sanders

Publications and source records attributed to P A Sanders.

At least 19 recordsLinked to original sources
PubMed2001

A case-control study examining the role of physical trauma in the onset of rheumatoid arthritis.

OBJECTIVE: To investigate whether physical trauma may precipitate the onset of rheumatoid arthritis (RA). METHOD: In a case-control study comparing RA out-patients with controls attending non-rheumatology out-patient clinics, 262 patients and 262 age- and sex-matched controls completed a postal questionnaire or were interviewed about any physical trauma in the 6 months before the onset of their symptoms. RESULTS: Fifty-five (21%) of the RA patients reported significant physical trauma in the 6 months before the onset of their disease, compared with only 17 (6.5%) of the controls (P<0.00001). A preceding history of physical trauma was significantly more common in RA patients who were seronegative for rheumatoid factor (P=0.03), but was not significantly associated with sex (P=0.78), age (P=0.64), a family history of RA (P=0.07) or type of occupation, defined as manual or sedentary (P=0.6). CONCLUSION: Physical trauma in the preceding 6 months is significantly associated with the onset of RA.

Arthritis, Rheumatoid↗
PubMed1996

Soluble L-selectin in the connective tissue diseases.

Plasma levels of the leucocyte adhesion molecule L-selectin were measured by ELISA in 41 patients with rheumatoid arthritis, 18 with ankylosing spondylitis, 18 with systemic sclerosis and 27 with vasculitis together with 42 age- and sex-matched controls. Low levels of soluble L-selectin were found in systemic sclerosis (797 +/- 302 ng/ml, P < 0.05) and vasculitis (941 +/- 329 ng/ml, P < 0.05) relative to controls (1244 +/- 269 ng/ml). The exact reasons for low levels of soluble L-selectin are unclear, but may reflect reduced shedding from leucocytes and/or strong binding to its cell membrane ligand(s). An approximate inverse relationship between soluble L-selectin and disease severity may have clinical relevance.

Adult↗
PubMed1995

Agranulocytosis in rheumatoid arthritis associated with long-term flucloxacillin for staphylococcal osteomyelitis.

Agranulocytosis and septicaemia developing in a patient with rheumatoid arthritis after 3 years' intermittent treatment with diclofenac, cimetidine and flucloxacillin for staphylococcal osteomyelitis is described. Treatment with recombinant granulocyte-colony-stimulating factor and high-dose methylprednisolone had no effect on the neutropenia which resolved on stopping all drug therapy. Relapse of agranulocytosis followed reintroduction of flucloxacillin and cimetidine 3 months later.

Aged↗
PubMed1993

Unusual DQA-DR haplotypes in rheumatoid vasculitis.

DQA and DQB variants and HLA haplotypes were defined in Caucasian subjects with rheumatoid arthritis (RA), in a rheumatoid subset characterized clinically by extra-articular features of major vasculitis, and in controls. DQ variants were defined using a panel of sequence specific oligonucleotide probes. In RA subjects without extra-articular features the frequency of DQB*0301 was significantly increased but this was secondary to the main association with DR4. In rheumatoid vasculitis by contrast, DQB*0302 rather than DQB*0301 was increased in frequency, in addition to an increase of C4A null alleles. Family studies showed that DR4 negative haplotypes had an increased frequency of unusual DR-DQA combinations as compared to other rheumatoid subsets. These findings are in keeping with the concept that genes within the MHC other than DR4 have a disease-modifying role in rheumatoid subsets. HLA haplotypes were defined in a family where the proband has RA and Felty's syndrome and an affected sister has rheumatoid vasculitis. These siblings share a DR4 bearing haplotype typing for DQB*0301, and the sister with rheumatoid vasculitis has a DR4 negative haplotype carrying a C4A null allele and an unusual DR-DQA combination.

Arthritis, Rheumatoid↗
PubMed1993

HLA associations in subjects with rheumatoid arthritis and bronchiectasis but not with other pulmonary complications of rheumatoid disease.

We have examined HLA-DR, DQA and DQB variants in 72 controls, 153 subjects with RA without extra-articular features and in subjects with the rheumatoid pulmonary complications of interstitial fibrosis (23) peripheral airways disease (13) and in 41 subjects with RA and bronchiectasis. Subjects with RA alone showed the expected association with HLA-DR4 (79%) but those with RA and co-existent pulmonary fibrosis were less likely to be DR4 positive (61%). No other HLA-DR variants were significantly increased in the different disease groups. HLA-DQB1*0501 which types serologically as DQw1 was increased in subjects with RA and peripheral airways disease as compared to rheumatoid subjects with normal lung function, but these differences were not statistically significant. DQB1*0601 was increased in subjects with bronchiectasis with or without RA (but only significantly so in RA-BR subjects) DQB1*0301, DQB1*0201 and DQA1*0501 frequencies were also increased in subjects with RA and bronchiectasis as compared to those with RA alone.

Aged↗
PubMed1992

Complement C4 null alleles as a marker of gold or D-penicillamine toxicity in the treatment of rheumatoid arthritis.

C4 null alleles and HLA-DR antigens were defined in 48 rheumatoid arthritis (RA) subjects who had developed renal or heamatological side effects to gold or penicillamine, as compared to 33 RA subjects who had received the drugs for similar time periods without developing side effects. A C4A null allele was found in 56% of subjects with and 31% of those without side effects (P = 0.027, relative risk 2.8). A similar but statistically non-significant trend was observed with the C4B null allele (P = 0.64) resulting in a higher risk of drug toxicity in rheumatoid patients bearing either a C4A or C4B null allele (relative risk 5.7). Frequencies of DR3 and DR4 were similar in the two groups.

Alleles↗
PubMed1991

Immunogenetic heterogeneity in rheumatoid disease as illustrated by different MHC associations (DQ, Dw and C4) in articular and extra-articular subsets.

Genetic variants at DRB1 (Dw subtypes), DQB, and C4 loci were compared in rheumatoid disease subjects with or without the extra-articular feature of Felty's syndrome or major vasculitis. DR4 positive subjects with rheumatoid arthritis alone showed no preferential associations with DQB or Dw variants or with C4 null alleles. Felty's subjects showed associations with the DQB encoded DQw7 allele and with the C4B null allele but no preferential associations with any Dw subtype of DR4. By contrast DR4 +ve rheumatoid-vasculitic subjects showed associations with the Dw14 as well as with DQw7 and the C4A null allele. These different MHC associations in different clinical disease subsets show that rheumatoid disease is immunogenetically heterogeneous and suggest that MHC genes outside the DRB1 locus may also influence susceptibility or modify expression of the rheumatoid disease process.

Alleles↗
PubMed1991

Ig CH and D14S1 variants in rheumatoid arthritis--linkage and association studies.

We have looked for an effect of 14th chromosomal genes linked to immunoglobulin heavy chain (IgCH) or D14S1 regions on susceptibility to rheumatoid arthritis (RA) by both linkage (sibling pair analysis) and association studies. There was no overall linkage between RA and either IgCH or D14S1. However, Gm haplotype similarity in affected siblings appeared greater in either DR4-positive as compared to DR4-negative sibships or in sibships without clinical or serological evidence of autoimmune thyroid disease when compared to sibships with such evidence. In association studies there were no associations at the D14S1 locus. Within the Ig CH region there were no overall associations. However, within the RA population G1m (z) and G3m (g) both appeared less frequent in DR4-negative RA versus both DR4-positive RA and versus control groups. Analysis of DNA variants at Ig CH loci showed differences at the gamma 4 locus with a 9.0 kb fragment appearing less frequently in DR4-positive RA versus DR4-negative RA and control groups. The results suggest a weak or HLA-DR dependent effect of genes linked to the Ig CH region on susceptibility to RA.

Arthritis, Rheumatoid↗
PubMed1991

Articular disease severity in rheumatoid subjects with and without Felty's syndrome.

Articular disease severity as measured by a radiographic score of hands and feet was compared in rheumatoid subjects with (21) and without (170) Felty's syndrome. Disease duration was a major determinant of joint destruction. When this was taken into consideration radiographic scores were no higher in the Felty's group than in rheumatoid subjects without Felty's syndrome. Immunogenetic associations previously described in Felty's syndrome are unlikely therefore to represent non-specific markers of disease severity and more likely to represent markers of extra-articular disease.

Arthritis, Rheumatoid↗
PubMed1990

Age and year of onset differences in siblings with rheumatoid arthritis.

Differences in age of disease onset and calendar year of onset were studied in 46 rheumatoid arthritis (RA) sibling pairs and in unrelated pairs of RA patients attending a hospital clinic. Mean age of onset and calendar year of onset differences in each group were similar. These results support the theory that RA is caused by an interaction of genetic and environmental factors and provide evidence against a single environmental transmissible cause.

Adult↗
PubMed1990

Studies of a C2 DNA polymorphism in RA, Felty's and normal subjects.

A restriction fragment length polymorphism at the C2 locus was studied in rheumatoid arthritis (RA), Felty's and control subjects. No association was found between any C2 variant and either RA itself or within the rheumatoid population with Felty's syndrome. The C2 DNA polymorphism can be used to subdivide Bf*S- as well as Bf*F-bearing haplotypes. The 2.65-kb C2 DNA allele showed allelic association with HLA-B44 and C4B*Q0 and may help to further characterize the haplotype B44-Bf*S-C4A*3-C4B*Q0-DR4, which has previously been described in Felty's syndrome.

Alleles↗
PubMed1989

Haplotypes bearing HLA-A, -B, and -DR: Bf and C4 genes in rheumatoid arthritis families.

We have compared haplotypes bearing HLA-A, -B, -DR; Bf and C4 genes in 54 rheumatoid arthritis (RA) and 24 control families. There was no statistically significant differences in C4A or C4B gene frequencies between RA and control groups, although there were trends for C4B*Q0 to be reduced and C4B2 to be increased in DR4 positive RA compared with DR4 positive controls. The lack of any strong association between C4 variants and RA overall makes it unlikely that the association between RA and genes within the MHS represents a direct effect of variants within the C4A or C4B loci themselves. On comparison of DR4-bearing haplotypes, the haplotype B15-BfS-DR4 was increased fourfold and the B44-Bfs-DR4 haplotype was less frequent in the RA group. When C4 variants were also considered, the haplotype B44-C4B*Q0-C4A3-BfS-DR4 was nine times less frequent in RA patients than in controls. The observation that different DR4 bearing haplotypes may confer either increased or decreased susceptibility to RA suggests either that it is unlikely that DR4 itself is involved in the disease process or that specific haplotypic combinations are important. Thirty-two RA patients were HLA-DR4 negative. No single DR4 negative haplotype was found to confer significantly increased susceptibility to RA.

Arthritis, Rheumatoid↗
PubMed1989

Immunoglobulin allotypes in rheumatoid arthritis.

The HLA region of chromosome 6 may account for as little as 20% of the genetic contribution to rheumatoid arthritis (RA). Previous studies have shown associations with immunoglobulin heavy chain allotypes (Gm) coded for by genes on chromosome 14. We review evidence that G1m(x)-bearing haplotypes are associated with DR4-positive, but not DR4-negative RA. A differing Gm association has been reported in two studies of RA patients with circulating antibodies to native type II collagen, which might constitute a specific genetic subgroup. A family study has shown no evidence for genetic linkage between Gm allotypes and susceptibility to RA. It is possible that Gm (or linked 14th chromosomal genes) may influence susceptibility to RA by interacting with different genes within the HLA region. Immunoglobulin light chain allotypes (Km) coded by genes on chromosome 2 show no consistent association with RA.

Arthritis, Rheumatoid↗