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Biomedical subjects

W A Liston

Publications and source records attributed to W A Liston.

At least 19 recordsLinked to original sources
PubMed1992

Prenatal screening for cystic fibrosis.

Screening for carriers of CF (cystic fibrosis) is now possible but the best way of delivering such a service is unknown. In one model 4348 women attending antenatal clinics in an Edinburgh maternity hospital were invited to participate in a trial of prenatal screening. Mouthwash samples were tested for six CF alleles (85% of mutant genes) and when a woman was found to be a CF carrier her partner was also tested. Heterozygous couples were offered prenatal diagnosis. 609 (14%) women declined to enter the trial and another 574 (13%) were not screened, usually because of late booking. Among the remaining 3165 women there were 111 carriers of a CF gene (1 in 29). 4 of these 111 had carrier partners and these couples opted for prenatal diagnosis, the 1 pregnancy with an affected fetus being terminated. The psychological impact of screening was assessed by the general health questionnaire. There was a significant increase in stress at the time of the test result among women identified as carriers. However, this disappeared when their male partners tested normal and did not reappear later in the pregnancy. By providing time for couples to discuss the possibility of screening and by offering the test at a point (the antenatal booking clinic) at which most pregnant women are seen, this approach has advantages, provided that counselling is readily available.

Alleles↗
PubMed1992

Prenatal cystic fibrosis carrier testing: designing an information leaflet to meet the specific needs of the target population.

A questionnaire was given to 180 patients in an antenatal clinic, who were eligible to enter a pilot trial of cystic fibrosis (CF) carrier testing, seeking their views on the information leaflet inviting them to participate; 161 patients (89%) entered the trial and 145 patients (81%) responded to the questionnaire, including 10 who did not enter the trial. Ninety-six percent of these found the leaflet easy to understand, and 97% of those partners who read the leaflet also found it easy to understand. Fifteen percent of patients thought the leaflet should give additional information. Most (92%) had heard of CF before reading the leaflet, television being the most common source of information. Although avoiding the birth of a child with CF was the reason most patients gave for wishing to be screened, almost as many were interested to know their carrier status. The decision to accept or decline testing was taken in conjunction with their partner by 63% of women. Of those who were screened, 59% stated that taking the test made them feel reassured, while 38% felt slightly apprehensive. It was concluded that, with a number of minor amendments, the leaflet met the specific needs of the target patient population.

Attitude to Health↗
PubMed1992

An exclusion map for pre-eclampsia: assuming autosomal recessive inheritance.

Pre-eclampsia is a common complication of the second half of pregnancy that is associated with substantial fetal and maternal morbidity. Although the genetic basis of the disorder is unclear, epidemiological studies suggest that it occurs predominantly in the first pregnancies of women who are homozygous for a relatively common susceptibility gene. Using this epidemiological model, we have begun to construct an exclusion map by using both candidate genes and random DNA markers on a panel of two-generation families in which pre-eclampsia was rigorously defined. No evidence was found for linkage to the HLA region or to several genes implicated in the pathogenesis of hypertension.

Chromosomes, Human, Pair 1↗
PubMed1991

Immunocytochemical localization of neutrophil elastase in term placenta decidua and myometrium in pregnancy-induced hypertension.

OBJECTIVE: The aim of the study was to determine whether there was evidence of elastase containing neutrophils at the materno-fetal interface in women with pregnancy-induced hypertension (PIH). DESIGN: An observational prospective study. SETTING: The Simpson Memorial Maternal Pavilion Edinburgh. METHODS: Placentas were obtained at vaginal or abdominal delivery from 51 consecutive women, 23 had normal pregnancies (13 caesarean sections) and 28 had PIH (18 caesarean sections). An immunocytochemical technique was used to localize elastase containing neutrophils in the placenta, decidua and myometrium. MAIN OUTCOME MEASURES: The numbers of positively stained cells, estimated subjectively as minimal, moderate or heavy, in subchorionic plate, perivillous fibrin and decidua. RESULTS: In both normal and PIH pregnancies neutrophils were absent from the myometrium. However, elastase containing neutrophils were located in areas of fibrin in the subchorionic plate and around the villi although there was no significant difference between the normal and PIH group. Neutrophils were also located in the fibrin of the decidua and in this case the number was significantly greater in the PIH group than in the normal group and correlated with plasma urate. CONCLUSION: The release of neutrophil elastase in the decidua could contribute to the vascular damage evident in PIH.

Adult↗
PubMed1991

Is genetic susceptibility to pre-eclampsia conferred by homozygosity for the same single recessive gene in mother and fetus?

OBJECTIVE: To determine whether any simple, purely genetic mechanism can account for susceptibility to pre-eclampsia. DESIGN: Six simple Mendelian models of inheritance were considered, and predictions concerning the incidence of pre-eclampsia in various family members of index cases were calculated for each genetic model. Data were then extracted from published family studies in which a suitable disease definition had been used, and compared to our theoretical expectations. RESULTS: Only one of the genetic models considered, in which both mother and fetus must express the same recessive gene to confer susceptibility, was consistent with the observed incidence values for relatives of index cases. This model was also consistent with the putative association with HLA-DR4, but could not account for the comparative rarity of pre-eclampsia in parous women. CONCLUSION: Homozygosity for a single recessive gene shared by mother and fetus, unlike five other genetic mechanisms tested, is consistent with published family studies in pre-eclampsia, and should be considered the best working hypothesis at present.

Disease Susceptibility↗
PubMed1990

First-trimester maternal serum biochemical indicators in Down syndrome.

A set of 21 early maternal serum samples (19 first-trimester and two at 14 weeks) from pregnancies resulting in a child with Down syndrome was matched for gestation and length of storage with 63 samples from unaffected pregnancies. The concentrations of alpha-fetoprotein (AFP), unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG), pregnancy-specific beta 1-glycoprotein (SP1), and placental alkaline phosphatase (PALP) were measured. The ratios of the medians for Down syndrome pregnancies compared with the medians for controls were AFP 0.71, uE3 0.67, hCG 1.43, SP1 0.79, and PALP 0.92. Although the differences between the medians for affected and unaffected pregnancies were not significant, the trends for AFP, uE3, and hCG confirm earlier findings on first-trimester samples.

Alkaline Phosphatase↗
PubMed1990

Pre-eclampsia is associated with HLA-DR4 sharing between mother and fetus.

Full HLA-A,B and DR typing was carried out on 92 women with proteinuric pre-eclampsia, 80 of their husbands and 46 of their babies. The results were compared with corresponding data from 65 normotensive pregnancies involving primiparous women. The frequency of HLA-DR4 was increased in the pre-eclamptic women (RR 3.1; p less than 0.005) and in the babies of pre-eclamptic pregnancies (RR 2.6; p less than 0.03). The strongest association, however, was with sharing of HLA-DR4 between mother and fetus (RR 4.2; p = 0.01). There was no increase in HLA antigen sharing in general between spouses or maternal-fetal pairs in pre-eclampsia. Nor did pre-eclamptic women exhibit increased homozygosity in general at any HLA locus. We conclude that genetic susceptibility to pre-eclampsia depends at least partly on fetomaternal compatibility for a gene or genes associated with HLA-DR4.

Female↗
PubMed1989

Association between susceptibility to pre-eclampsia within families and HLA DR4.

56 women who had had proteinuric pre-eclampsia and who had parous sisters were studied. In first pregnancy, proteinuric pre-eclampsia was more common in the sisters than in the maternity hospital population (8/71 [11%] vs 41/1978 [2%]); the relative risk was 6.0. The frequency of HLA DR4 was higher in sisters with pregnancy-induced hypertension than in sisters with normotensive pregnancies (8/18 [44%] vs 10/54 [19%]) and more of them shared HLA DR4 with their spouses (4/14 [29%] vs 0/29). Genetic susceptibility to pre-eclampsia is associated with HLA DR4; it may be conferred by fetomaternal sharing of a single recessive HLA-linked gene.

Adult↗
PubMed1989

Prenatal exclusion testing for Huntington's disease: a problem of too much information.

At eight weeks of pregnancy a couple were informed that the prospective father's mother had died of Huntington's disease (HD). There were no living affected members in the immediate family to confirm the diagnosis. By inspection of the local genetic register, it was established that it was indeed HD segregating in the extended family. Genotyping of the prospective mother and father, the father's unaffected father, and his unaffected maternal grandmother was carried out using a battery of polymorphic DNA markers, including a new probe which has a very low recombination rate with the HD locus. Analysis of DNA from a chorionic villus sample taken at 10 weeks of pregnancy showed that the fetus must have inherited a chromosome from its father's affected mother. Its risk of developing HD was 47%. If the genotype of the unaffected maternal grandmother was taken into account, the risk was reduced to 42%. Neither risk was considered acceptable by the prospective parents and the pregnancy was terminated at 12 weeks' gestation. Prospects for future pregnancies are good, with a 50% chance of having a child whose risk of inheriting the HD gene is less than 1.5%. In retrospect it was noted that although genotyping of the maternal grandmother had refined the fetal risk, it had also nearly contributed to an inadvertent and unwanted predictive test for HD on the father. This case makes the point that in prenatal exclusion testing, linkage information must be generated with considerable care.

Adult↗
PubMed1987

Histocompatibility studies in pre-eclampsia.

Full HLA-A, B and DR types were obtained for 22 families (mothers, fathers and neonates) associated with severe (proteinuric) pre-eclampsia, 21 families associated with mild pre-eclampsia, and 132 families associated with normal pregnancies. There was an increased frequency of DR4 (relative risk 3.6: p less than 0.003, uncorrected) in both neonates and mothers of the severe pre-eclampsia families when compared to the normotensive controls. There were no significant differences between either pre-eclampsia group and controls in HLA antigen homozygosity, HLA antigen sharing or in lymphocytotoxin production.

Female↗
PubMed1987

Severe pre-eclampsia in multiparous women: indication of an environmental triggering agent?

Two case histories are described with conflicting implications for the etiopathogenesis of pre-eclampsia. In both, typical proteinuric pre-eclampsia developed despite a history of previous normotensive pregnancy. In the first case, the disease was associated with a change of husband, consistent with the view that pre-eclampsia arises from an inadequate maternal immune response to paternal antigens inherited by the fetus. The second case, however, concerned a woman who developed pre-eclampsia for the first time in her third pregnancy by the same reproductive partner. We conclude that either more than one underlying cause can result in the clinical syndrome of pre-eclampsia, or that pre-eclampsia is caused by an environmental factor. The possibility that pre-eclampsia may be initiated by an infectious agent is briefly explored in the light of the clinical histories described and well-established epidemiological, clinical and laboratory data.

Adult↗