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Biomedical subjects

R H Ward

Publications and source records attributed to R H Ward.

At least 91 records · Page 5Linked to original sources
PubMed1983

Genetic and sociocultural components of high blood pressure.

The cardiovascular diseases exert widely differing contributions to the total burden of mortality and morbidity in extant human populations. To a large extent these differences are a reflection of the variable distribution of specific antecedent risk factors. For one such risk factor, blood pressure, there is considerable variability in its distribution between different ethnic groups, especially between traditional and nontraditional societies. Intensive epidemiological studies in Western societies, together with a number of cross-cultural comparisons, suggest that the major determinants of high blood pressure are likely to be a constellation of sociocultural factors, with genetic determination being limited to the interaction between genotype and environment. Studies of populations in sociocultural transition offer an unique opportunity to identify the relative influence of specific sociocultural factors on the rate of change of blood pressure. In addition, when the study of such populations is placed in a quasi-experimental context, genetic-environmental interactions may also be detected. This strategy is illustrated by a study of the changing blood pressure distribution in Tokelauan migrants. Such an approach requires the initial definition of a response variable which measures change in blood pressure as a consequence of migration. The response variable, which identifies the relative influence of concomitants such as weight, age, and obesity, can then be subjected to genetic analysis. In the Tokelau case, blood pressure response tends to be positive in migrants but negative in nonmigrants. Further statistical analysis indicates that there is a small proportion of high responders in both populations and that these cluster in families in the migrant population. However, estimates of the transmission parameter suggest that sociocultural transmission, rather than Mendelian segregation, is responsible. To date there is little evidence that genetic-environmental interactions have had any impact on the development of hypertension in this migrant population.

Age Factors↗
PubMed1983

Volumes of distribution of sodium and albumin in the sheep placenta.

The volumes of distribution of 22Na and 24Na, 51Cr-EDTA and albumin labelled with 131I and 125I were measured in cotyledons and skeletal muscle taken from pregnant sheep and the fetuses near term. Radiolabelled substances were injected through chronically implanted catheters 0.5-3.2 hr before removal of tissues in 'short-term' experiments and 24-26 hr before in 'long-term' experiments. Volumes of distribution were expressed as percentages of tissue weights. Cotyledonary water content was 81.5 +/- 0.6% (S.E. of mean) of wet weight (n = 10 sheep). Sodium content was 76.0 +/- 4.0 m-mole kg-1 wet weight (n = 4) and potassium content was 58.8 +/- 2.4 m-mole kg-1 wet weight (n = 4). In short-term studies cotyledonary spaces following injection into the fetal circulation were: Na, 20.5 +/- 0.9% (n = 10 sheep); Cr-EDTA, 19.5 +/- 1.2% (n = 3); and albumin, 2.8 +/- 0.3% (n = 11). The equivalent maternal cotyledonary spaces were: Na, 23.5 +/- 1.6%, or 22.1 +/- 1.6% when 'corrected' for fetal radioactivity (n = 8); and albumin, 4.7 +/- 0.8% (n = 8). Maternal and fetal cotyledonary sodium spaces were additive. Larger cotyledons had larger fetal sodium spaces. In long-term studies, the value for maternal albumin spaces was considerably higher 12.3 +/- 3.2% (n = 3), whereas that for fetal albumin spaces was only 3.9 +/- 0.4% (n = 4). The higher fetal sodium space of 24.9 +/- 1.0% (n = 4) in the long-term experiments was attributable to rising sodium counts in the maternal circulation. In the short-term experiments maternal skeletal muscle spaces were Na, 13.5 +/- 1.3% (n = 7) and albumin, 1.7 +/- 0.3% (n = 7), with higher values of 22.0% (n = 2) and 3.8 +/- 0.2% (n = 3) respectively in long-term experiments. In the short-term experiments fetal skeletal muscle spaces were Na, 32.8 +/- 3.2% (n = 7) and albumin, 2.5 +/- 0.3% (n = 10), with higher values of 39.7 +/- 7.4% (n = 4) and 16.2 +/- 0.6% (n = 4) respectively in long-term experiments.

Animals↗
PubMed1983

Immunological tolerance induced by in utero injection.

Intrauterine injection of human whole blood into rabbit and rhesus monkey fetuses was found to result in long lasting unresponsiveness to human serum albumin. Intrauterine injection of viable allogeneic bone marrow cells into rabbit fetuses was without any apparent harmful effect and also resulted in permanent unresponsiveness demonstrated by donor red cell survival studies. The implication of these findings in respect of using this approach towards the correction of certain inherited diseases in man is discussed.

Animals↗
PubMed1983

Evaluating pedigree data. II. Identifying the cause of error in families with inconsistencies.

Pedigree data can be evaluated, and subsequently corrected, by analysis of the distribution of genetic markers, taking account of the possibility of mistyping . Using a model of pedigree error developed previously, we obtained the maximum likelihood estimates of error parameters in pedigree data from Tokelau. Posterior probabilities for the possible true relationships in each family are conditional on the putative relationships and the marker data are calculated using the parameter estimates. These probabilities are used as a basis for discriminating between pedigree error and genetic marker errors in families where inconsistencies have been observed. When applied to the Tokelau data and compared with the results of retyping inconsistent families, these statistical procedures are able to discriminate between pedigree and marker error, with approximately 90% accuracy, for families with two or more offspring. The large proportion of inconsistencies inferred to be due to marker error (61%) indicates the importance of discriminating between error sources when judging the reliability of putative relationship data. Application of our model of pedigree error has proved to be an efficient way of determining and subsequently correcting sources of error in extensive pedigree data collected in large surveys.

Female↗
PubMed1983

Genetic epidemiology as a tool for investigating rheumatic disease.

Both genetic and environmental factors are likely to contribute to the etiology of the rheumatic diseases. The relative contribution of genes and environment to the observed variability in prevalence and expression of rheumatic disease in different populations can only be assessed by procedures designed to identify both genetic and environmental influences. By applying the new discipline of genetic epidemiology to study familial aggregation, association with genetic markers, segregation, and linkage analysis, our understanding of rheumatic disease is likely to be substantially advanced during the next decade.

Disease Susceptibility↗
PubMed1983

Evaluating pedigree data. I. The estimation of pedigree error in the presence of marker mistyping.

Pedigrees used in the analysis of genetic or medical data are usually ascertained from sources subject to a variety of errors including misidentification of individuals, faults in historical documents or record linkage, nonpaternity, and unidentified adoption. Genetic markers can be used to verify putative family and pedigree data through the search for inconsistencies, or genetic exclusions, between putative parents and offspring. The probability of observing an exclusion given the occurrence of an error depends upon the gene frequencies at the loci under study and the forms of error. In addition, inconsistencies can arise from laboratory errors in marker determination. Together, these problems make the proper statistical analysis of such data desirable. Here we give a model that specifies the combined effects of various kinds of pedigree error along with genetic marker error. This model allows the maximum-likelihood estimation of the rates of various forms of pedigree error and laboratory error from genetic marker data collected on putative families. The method is illustrated by applying it to data obtained from a South Pacific island population, Tokelau. From the observed distribution of genetic marker inconsistencies between the parents and offspring of putative families, derived from the extensive genealogy of this population, we are able to estimate that the error of a paternal link is 4%, the error of a maternal link is zero, and the overall system typing error is 1%.

Alleles↗
PubMed1982

Reduced Coxsackie antibody titres in type 1 (insulin-dependent) diabetic patients presenting during an outbreak of Coxsackie B3 and B4 infection.

The potential role of antecedent viral infection in the pathogenesis of Type 1 (insulin-dependent) diabetes was investigated by measuring antibody titres to several viruses in serum obtained at the time of diagnosis of diabetes. An outbreak of Coxsackie B4 infection followed by a wave of Coxsackie B3 and B5 infections occurred in Seattle during the time viral serology was obtained in the diabetic patients. Antibody titres to Cocksackie B5 and Influenza A and B viruses were comparable in diabetics and matched control subjects, but antibody titres to Cocksackie B3 and B4 were lower in the diabetics and a low antibody titre to Coxsackie B3/B4 was associated with a significantly increased relative risk of diabetes.

Antibodies, Viral↗
PubMed1981

Aqueous-venous shunt for glaucoma. A further report.

The aqueous-venous shunt procedure is a new microsurgical procedure for the relief of glaucoma. The procedure is therapeutically effective in control of glaucoma, is relatively simple to perform, is associated with low risk, and is well tolerated. As measured by tonography and clinical observations, intraocular pressure reduction following the procedure is due mainly to an improvement in aqueous outflow facility. It can be considered clinically as a useful alternative in the management of selected cases of open angle glaucoma.

Adolescent↗
PubMed1981

Four years' experience of maternal alpha-fetoprotein screening and its effect on the pattern of antenatal care.

Estimation of alpha-fetoprotein (A.F.P.) in maternal serum was used as a screening method for the detection of fetal neural tube defect (N.T.D.) in 7315 women over a four year period. Of these, 5668 pregnancies were tested between 15 and 21 weeks. Action was advised in 129 patients (2.3 per cent). In 74 patients, the only action required was reviewing the notes, including the report of any ultrasound examination, and repeating the blood A.F.P. Detailed ultrasound including scanning the fetal spine was requested in 47 patients and amniocentesis was advised in 19 of these (0.33 per cent). In practice the incidence of amniocentesis was 0.28 per cent as three patients declined our advise. The programme gave detection rates between 15 and 21 weeks of 100 per cent and 75 per cent respectively for anencephaly and open spina bifida. A high fetal mortality was associated with persistently elevated blood A.F.P. levels whether amniocentesis was performed or not.

Amniocentesis↗
PubMed1981

Obstetric outcome and problems of mid-trimester fetal blood sampling for antenatal diagnosis.

Detailed follow-up is presented of 335 pregnancies in which mid-trimester fetal blood sampling was performed for the diagnosis of a haemoglobinopathy, mostly beta-thalassemia. There were three twin pregnancies. Thirty-eight fetuses were lost including four in whom a diagnosis of thalassemia major was made. Placentacentesis was particularly associated with fetal vessel trauma, exsanguination and early intrauterine fetal death, while late complications associated with fetoscopy or failed fetoscopy necessitating subsequent placentacentesis included spontaneous abortion, leakage of amniotic fluid and premature onset of labour.

Abortion, Spontaneous↗
PubMed1980

Maternofetal electrical potential difference in conscious sheep: effect of fetal death or acidosis.

Maternofetal electrical potential difference (pd) was measured in conscious pregnant ewes during the last 40 days of gestation. Recordings were made via catheters filled with saline solution and chronically implanted in at least two blood vessels on either side of the placenta. The pd ranged between -14 and 93 mV, mother positive. The mean potential declined from 54 +/- 8 mV (n = 5) immediately after operation to 28 +/- 7 mV after 48 hours and did not alter significantly thereafter. The pd increased with fetal acidosis induced by infusion of acid. The mean slope was 54 +/- 11 mV per pH unit (n = eight infusions). The pd rose when the fetus died, but was abolished by killing the ewe. The pd 1 day postoperatively fell with increasing gestational age (pd = 164 - 1.00 x days; p < 0.05, n = 41 sheep).

Allantois↗
PubMed1980

Effect of introducing antenatal diagnosis on reproductive behaviour of families at risk for thalassaemia major.

Families who were at risk of producing a child with thalassaemia major were studied to determine the sequential effects on their reproductive behaviour of knowing the risk and, subsequently, of knowing that antenatal diagnosis was available. Knowing the risk caused them virtually to stop reproduction and to seek termination of 70% of pregnancies, most of which were accidental. The introduction of antenatal diagnosis in 1975 permitted the resumption of nearly normal reproduction by at-risk families, with fewer than 30% of pregnancies being terminated for thalassaemia major. All couples at risk for thalassaemia major should be detected and counselled before they produce an affected child; responsibility for either choosing or refusing antenatal diagnosis should be theirs alone.

Abortion, Induced↗
PubMed1980

Haematological aspects of antenatal diagnosis for thalassaemia in Britain.

The results are described of 200 antenatal diagnostic tests for haemoglobinopathies performed on samples of fetal blood obtained during the second trimester of pregnancy. Haemoglobin A synthesis in the fetus was measured by incorporation of tritiated leucine in vitro and separation of the globin chains on CM23 columns. The range of HbA synthesis detected was 3.5-8.0% in normal fetuses, 2.0-5.0% in fetuses with thalassaemia trait, and less than 1.6% in fetuses with thalassaemia major. There were eight cases in which other haemoglobinopathies were diagnosed. 29% of the pregnancies were terminated because thalassaemia major was diagnosed, and 9.5% of the remaining healthy fetuses were lost for obstetric reasons. Follow up has been possible for 96% of the 124 surviving babies and three misdiagnoses have come to light; one false positive (0.5%) and two false negatives (1%). These figures represent a first effort at antenatal diagnosis for haemoglobinopathies and it is likely that they will improve with the passage of time.

Chromatography, Ion Exchange↗