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Biomedical subjects

J D Mathews

Publications and source records attributed to J D Mathews.

At least 73 records · Page 4Linked to original sources
PubMed1986

Genetic markers in rheumatoid arthritis relationship to toxicity from D-penicillamine.

In a 3-centre study involving 144 patients with rheumatoid arthritis (RA), a relationship between side effects from D-penicillamine and HLA antigens, allotypic markers of the IgG heavy chain (Gm) and allotypes of complement components Bf, C4A and C4B was sought. There was a significant association between proteinuria induced by D-penicillamine and the antigens DR3 and B8. However, the presence of DR2 seemed to protect against the development of proteinuria. Thrombocytopenia from D-penicillamine was significantly associated with HLA-A1 and DR4; 15 of 23 patients who possessed both antigens developed thrombocytopenia (p less than 0.001 uncorrected, approximate relative risk (RR) = 5.5). A null complement allele located at the C4B locus (C4BQO) was also associated with thrombocytopenia from D-penicillamine (p less than 0.005, RR = 17.3). Our study confirms the findings from other series which indicate that there is a genetic predisposition for the development of proteinuria from D-penicillamine in RA and suggests that this may also be the case in D-penicillamine induced thrombocytopenia.

Arthritis, Rheumatoid↗
PubMed1985

Twin concordance for a binary trait. II. Nested analysis of ever-smoking and ex-smoking traits and unnested analysis of a "committed-smoking" trait.

Twin concordance rates for a binary trait can provide information about causes of trait variation. However, if trait prevalence varies with age (or birth cohort) or between the sexes, trait concordance rates will be artificially inflated because of the matching within pairs of twins. Our previous paper showed how to minimize the effects of such confounding by using logistic regression to model trait prevalence as a function of age and sex and that the binary correlation coefficient was useful as a measure of concordance that can be adjusted for trait prevalence. This method is extended here to allow for nested analyses and is applied to the smoking habits of a sample of 3,807 pairs of adult twins. For monozygotic (MZ) twins, the correlation coefficients for the binary trait of "ever-smoking" (males: .50 +/- .04; females: .60 +/- .02) were significantly greater than for dizygotic (DZ) twins (males: .37 +/- .05; females: .31 +/- .04; unlike-sex pairs: .21 +/- .03). For "giving-up smoking," given that both twins were previously smokers, the correlations for MZ twins (males: .37 +/- .07; females: .29 +/- .05) were also greater than for DZ twins (males: .11 +/- .09; females: .26 +/- .08; unlike-sex pairs: .13 +/- .06), although the difference was not statistically significant for females. Current smokers who had been smoking for at least 10 years were arbitrarily defined as "committed-smokers." The binary trait of "committed-smoking" was more strongly correlated in MZ twins (males: .41 +/- .06; females: .41 +/- .04) than in DZ twins (males: .22 +/- .08; females: .18 +/- .05; unlike-sex pairs: .16 +/- .05). These observations suggest that as well as depending on socially determined environmental factors, smoking behavior is influenced by genetic factors and/or by environmental factors unique to the MZ twin environment, which are of particular importance as determinants of "committed-smoking." There is a need for further research to investigate the personal characteristics of "committed-smokers" and to seek intervention strategies that are more suited to the needs of individual smokers.

Adult↗
PubMed1985

Defective reticuloendothelial system C3b mediated clearance in rheumatoid arthritis and vasculitis.

C3b receptor mediated clearance by the reticuloendothelial system (RES) was tested in vivo using autologous C3b coated, technetium labelled erythrocytes in patients with rheumatoid arthritis (RA) and rheumatoid vasculitis. Diminished C3b mediated erythrocyte clearance was found in all patients with rheumatoid vasculitis and some patients with active RA. Normal C3b mediated clearance was found in some patients with previous vasculitis, in remission when tested. These results are consistent with the hypothesis that acquired dysfunction of RES C3b receptors is implicated in the pathogenesis of rheumatoid vasculitis.

Adolescent↗
PubMed1984

Further look at dextropropoxyphene with or without paracetamol in the treatment of arthritis.

The analgesic effects of dextropropoxyphene and paracetamol and that of a combination of the two drugs were assessed in 24 patients who suffered from either rheumatoid arthritis or osteoarthritis. Dextropropoxyphene, which had a marginal effect on pain score, led to a more significant effect on patient well-being, particularly when it was the first drug given in the sequence. The addition of paracetamol had more of a negative than a positive effect on pain score and well-being.

Acetaminophen↗
PubMed1984

Genetic Analysis Workshop II: pedigree analysis of a binary trait without assuming an underlying liability.

A model for concordance in a binary measure that does not rely on the assumption of an underlying latent liability dichotomized about a threshold has been demonstrated for twin pairs [Hannah et al, 1983]. It is extended here to pedigrees of arbitrary structure by making an assumption that is, for small incidence rates, almost equivalent to postulating that relative risks are multiplicative. The model is applied to the workshop data to determine the extent to which the known structure of the simulated models can be recovered.

Alleles↗
PubMed1983

NHMRC workshop on non-pharmacological methods of lowering blood pressure. Is alcohol use a preventable cause of hypertension?

There is good evidence that hypertension is more frequently observed in alcohol-users than in non-users, and that the prevalence of hypertension is proportional to the average dose of alcohol consumed. If this association is causal, the 20% to 50% of hypertension in middle-aged Australian men which is attributable to alcohol use could prove to be entirely preventable. On the other hand, if the association is largely secondary, that is, if alcohol use and hypertension share genetic and other causes in common, then intervention to reduce alcohol consumption could have little effect on the prevalence of hypertension. Further work is needed to study the mechanisms by which alcohol use may cause hypertension, to identify the genetic factors which may determine susceptibility to hypertension in alcohol-users, and to carry out controlled intervention studies to test the hypothesis that alcohol use is a reversible cause of hypertension.

Alcohol Drinking↗
PubMed1983

Twin concordance for a binary trait. I. Statistical models illustrated with data on drinking status.

A flexible method based on maximum likelihood theory is introduced for the analysis of binary response data in twins. The method allows for explanatory variables such as age and sex, is free of the untestable distributional assumption of bivariate normality of liability, and makes more efficient use of the data available. The method is illustrated with preliminary data on drinking status in adult twins. Although there is some bias in the ascertainment of male dizygous twins, the results suggest that monozygous twins are more concordant than dizygous twins for drinking status.

Alcohol Drinking↗
PubMed1983

Extensions to multivariate normal models for pedigree analysis. II. Modeling the effect of shared environment in the analysis of variation in blood lead levels.

A multivariate normal model for pedigree analysis is applied to blood lead measurements from 617 individuals in 80 families in Melbourne, Australia, studied in 1977-1978. A new method is introduced for estimating time dependence of the family covariance matrix for blood lead levels; this time dependence can be interpreted as arising from the effects of common family environment on blood lead levels. Methods for the testing of assumptions and detection of outlying pedigrees and outlying individuals are applied. No correlation between blood lead levels of spouses was observed, but an effect of shared family environment was suggested by the difference between an estimated sibling correlation of about 0.5 for young sibling pairs living together and of about 0.1 for older siblings no longer living together. As there was no significant polygenic additive effect, the non-zero correlation between older siblings is more likely to be due to continuing effects of (environmental) factors shared in youth, rather than to a polygenic dominant effect. It is estimated that smoking 20 cigarettes per day is associated with an increase of about 12 per cent in blood lead level.

Adolescent↗
PubMed1983

HLA and Gm genes in systemic lupus erythematosus.

HLA and Gm phenotypes were compared in 53 patients with unequivocal systemic lupus erythematosus (SLE) and in 180 healthy subjects. SLE was associated with HLA-B8 (relative risk (RR) = 3.5, P less than 0.001) and with HLA-DR3 (RR = 2.8, P less than 0.01). There was an increased risk of SLE with HLA-B8/B27 (RR = 27.6) and with HLA-B15/B35 (RR greater than 13) and, in contrast, the risk was decreased in subjects with HLA-B40 (RR = 0.3). The risk of SLE in subjects who were heterozygous for the Gm phenotypes a,f,x; b,g was increased (RR = 2.0, P = 0.03) relative to the risk in subjects who were homozygous for these Gm phenotypes. These findings suggest that susceptibility to SLE is influenced by one or more genes in linkage disequilibrium with the HLA-B8-DR3 haplotype, by "augmentor" or "protector" genes associated with other HLA antigens and by separate genes, possibly VH genes, in linkage disequilibrium with the Gm (CH allotype) locus.

Genes, MHC Class II↗
PubMed1982

Clinical rheumatoid vasculitis associated with the B8 DR3 phenotype.

A statistically significant association of clinical rheumatoid vasculitis (excluding nodules or nail-fold infarcts only) with the HLA B8 DR3 phenotype was found when comparing 30 patients with vasculitis with 84 classic or definite rheumatoid patients without clinical vasculitis. The previously reported association on HLA DR4 with rheumatoid disease was also confirmed.

Arthritis, Rheumatoid↗
PubMed1982

Immunotherapy maintenance in acute non-lymphocytic leukaemia.

Between January 1975 and December 1977, 264 adult patients with acute non-lymphocytic leukaemia entered the Australian National Leukaemia Trial. Of 251 evaluable patients, three induction regimens achieved similar complete response (CR) rates. CROP (cytosine arabinoside, daunorubicin, vincristine, prednisolone) produced CR in 41% of patients, 7 and 3 (cytosine arabinoside, daunorubicin) in 42% and 7 and 3 plus hydroxyurea in 52%. Remission duration and survival were similar when induction regimens were compared. Forty-five patients reaching maintenance therapy were randomised to either chemo-immunotherapy (BCG plus intradermal leukaemic blast cells) or chemotherapy alone. The duration of CR in these two groups was almost identical, though patients receiving chemotherapy alone had prolonged survival (median 161 weeks) when compared to the chemo-immunotherapy group (84 weeks, p = 0 . 07). Institutions with less developed supportive facilities reported lower CR rates (p = 0 . 04). Leucocytosis (greater than 100 X 10(9)/1) and older age (greater than 50 years) were associated with shortened survival. The Trial has failed to show any advantage for this form of immunotherapy.

Acute Disease↗
PubMed1982

Extensions to multivariate normal models for pedigree analysis.

Lange, Westlake & Spence (1976) used the assumption of multivariate normality to apply a likelihood method to the analysis of quantitative traits measured over pedigrees. We now introduce a test of the assumption of multivariate normality and methods for the detection of outlying families and outlying individuals. We also introduce a method for the estimation of effects of measured genetic markers as variance components, a flexible parameterization to estimate effects of shared family environment, and a method to allow for the ascertainment of pedigrees through probands. These innovations have been applied using numerical methods for maximization of the likelihood. Simulation studies and available theory suggest that the likelihood ratio criterion used in significance testing follows the expected asymptotic distribution with sample sizes encountered in typical applications.

Family↗
PubMed1982

Immune complexes and vasoactivity generated from platelets in pre-eclampsia.

In vivo platelet activation by circulating immune complexes has been suggested as one of the underlying mechanisms in preeclampsia. Using a modification of the polyethylene glycol protein-A immune complex assay, immune complexes were found in excess of the equivalent of 20 micrograms/ml heat aggregated IgG in fourteen out of twenty patients diagnosed as having pre-eclampsia. Only six out of nineteen normal controls were found to have similar levels of immune complexes. Furthermore, using a small volume bio-assay method, concentrations of heat aggregated IgG in excess of 20 micrograms/ml were found to activate platelets to release sufficient concentrations of vasoactive agents to constrict a human blood vessel in vitro. These results support the hypothesis that in vivo platelet activation by immune complexes can release sufficient concentrations of vasoactive agents to contribute to the hypertension characteristic of pre-eclampsia.

Adolescent↗
PubMed1981

HLA-DR patterns in pernicious anaemia.

The pattern of HLA-DR antigens was studied in a group of 66 patients with Addisonian pernicious anaemia, comprising a subgroup of 18 patients with associated endocrine disease and a subgroup of 48 patients with no associated endocrine disease. Compared with a control group of 120 subjects all 66 patients showed an increase in HLA-DR2 and DR4 and a decrease in DR3 (p less than 0.02). Significant differences were also found between the endocrine and non-endocrine subgroups for patterns of HLA-DR antigens (p less than 0.005) and for pairwise combinations of HLA-DR antigens (p less than 0.01). Relative to controls, the endocrine subgroup showed an increase of HLA-DR3/DR4 (relative risk 4.0), contrasting with an increase of HLA-DR2/DR4 (relative risk 6.85) and DR4/DR5 (relative risk 5.38) in the non-endocrine subgroup. These observations suggest that HLA-DR antigens or closely linked genes may interact to influence susceptibility to pernicious anaemia (or endocrine disease, or both). Thus interactive effects related to HLA-DR2/DR4 and DR4/DR5 may predispose to pernicious anaemia without endocrine disease, whereas interactive effects related to HLA-DR3/DR4 may predispose to pernicious anaemia in association with endocrine disease.

Adult↗