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Biomedical subjects

R H Ward

Publications and source records attributed to R H Ward.

At least 109 records · Page 6Linked to original sources

Obstetric aspects of midtrimester fetal blood sampling by needling or fetoscopy.

We describe our experience at University College Hospital, London, with the first 135 patients submitted to midtrimester fetal blood sampling for antenatal diagnosis of beta-thalassaemia major, other thalassaemias and homozygous sickle cell disease. Blind needling and fetoscopy with sampling are evaluated and their application discussed. With experienced operators 9 per cent of patients experienced a fetal loss.

Anemia, Sickle Cell↗

A comparison of the genetic infrastructure of the Ye'cuana and the Yanomama: a likelihood analysis of genotypic variation among populations.

A general procedure is described for measuring and testing population differences in gametic frequencies. The total dispersion among populations is subdivided in hierachical fashion. The multiple-locus treatment is simply the sum of the single-locus analyses, provided gametic equilibrium obtains among the loci. In the event that gametic equilibrium does not obtain, correlations among loci need to be dealt with.--The analysis is then used to examine the genetic infrastructure of two Indian tribes from South America, the Ye'cuana (Makiritare) and the Yanomama. From historical evidence, we may identify several "clusters" of villages within each tribe. The demographic and cultural practices affecting village formation and the maintenance of peer integrity are rather different in these tribes, however, and lead us to postulate rather different patterns of genetic variation among villages. Analyses of five codominant two-allele loci, four dominant two-allele loci and two complex loci (with four codominant haplotypes each) demonstrate that Yanomama clusters are more disparate than Ye'cuana clusters, as would have been predicted on sociocultural grounds.

Blood Group Antigens↗

The treatment of mild adrenal hyperplasia and associated infertility with prednisone.

Thirty patients with mild post-pubertal adrenal hyperplasia, characterized by raised urinary 17-oxosteroid levels and variable combinations of irregular menses, hirsuties, infertility, and spontaneous abortion, were treated with 2.5 to 10 mg of prednisone per day and all conceived (55 pregnancies). With this treatment, regular, ovulatory cycles occurred immediately in 25 patients, and after two to six months, in the rest. Treatment reduced raised 17-oxosteroid levels to normal and brought about some improvement in hirsuties and acne. Forty-seven pregnancies ended in the birth of liveborn infants; one of these died of prematurity and another had congenital emphysema. One pregnancy was terminated, two were of unknown outcome and five (9.4%) ended in abortion. Before treatment, 20 out of 22 pregnancies (91%) had ended in abortion.

17-Ketosteroids↗

Fetomaternal transfer of glucose analogues by sheep placenta.

The steady-state permeability of the placenta to radiolabeled 3-O-methyl--D-glucopyranose (3MeG), alpha-methyl-D-glucopyranoside (AMG), and D-xylose was measured in chronically catheterized conscious sheep near term. Fetomaternal flux was calculated by application of Fick's principle to the uterine circulation after injection to the fetus. At a fetal glucose concentration of 10.2 +/- 1.25 mM, the permeability of 3MeG was half the maximal value of 59.5 +/- 11.2 ml/min found by extrapolation to zero glucose concentration. The permeability to 3MeG is considerably greater than is compatible with restricted diffusion, which together with the competitive effect of D-glucose suggests a carrier-mediated transfer mechanism. The permeability to AMG was less than 0.1 ml/min. The specificity pattern of sugar transport from the fetal side of the sheep placenta is different from that reported for gut lumen or kidney tubule in other species. D-Xylose is not metabolically inert after its injection into the fetal lamb.

Animals↗

Bidirectional sodium fluxes across the placenta of conscious sheep.

Conscious pregnant sheep in the last 3 wk of gestation were studied 1--3 days after surgery. Fetal plasma sodium concentration was significantly lower than maternal. A mean electrical potential difference (PD) of 34 +/- 4 (SE) mV (n = 24) was recorded between maternal and fetal intravascular catheters, the mother being positive with reference to fetus. Unidirectional fetomaternal (Jf leads to m) and maternofetal (Jm leads to f) sodium fluxes were determined by application of Fick's principle to uterine and umbilical circulations following injection of 22NaCl or 24NaCl to fetus or mother, respectively. Blood flows were measured by an antipyrine technique. Jm leads to f = 0.142 +/- 0.029 mmol/min (n = 10); Jf leads to m =0.137 +/- 0.015 mmol/min (n = 21). Jm leads to f increased as a linear function of calculated fetal weight. In seven sheep both Jm leads to f and Jf leads to m were measured in a single experiment. The measured ratio Jm leads to f/Jf leads to m was significantly different from the ratio predicted using Ussing's flux ratio equation. There is probably a transplacental sodium pump active in the direction fetus to mother.

Animals↗

A comparative study of plasma 17beta-oestradiol, progesterone, placental lactogen and chorionic gonadotrophin in abortion induced with intra-amniotic prostaglandin F2alpha.

Serial estimations were made in plasma of 17beta-oestradiol (E2), progesterone and human placental lactogen (HPL) in 43 patients and of human chorionic gonadotrophin (HCG) in 34 patients during mid-trimester abortions induced with intra-amniotic prostaglandin F2alpha (PGF2alpha. Mean plasma concentrations of all the hormones showed a progressive fall after PGF2alpha. There was no relationship between the fall in levels of progesterone, HPL and HCG and the induction-abortion interval, signs of fetal distress or of intrauterine fetal death. Both the control level and the rate of fall of E2 were related to the induction-abortion interval and a rapid decline preceded intrauterine fetal death. The relationships of the progesterone/E2 ratio and the amniotic fluid volume/progesterone ratio to the induction-abortion interval were examined. The variation in the time at which significant falls in the concentration of individual hormones occurred was probably related to their respective half-lives in plasma.

Abortifacient Agents↗

Placental permeability in the sheep.

The transplacental flux of different radiolabelled substances was measured, according to Fick's principle, in chronically catheterised pregnant sheep (124 to 143 days of gestation). Knowing the uterine blood flow, it was possible to calculate the net flux and derive a permeability coefficient, K. With 14C erythritol, K soon reaches its ultimate value, thus suggesting there is only one rate-limiting step to transfer and no significant middle compartment in the sheep placenta. The comparison of feto-maternal fluxes of different metabolically inert, lipid insoluble molecules (urea, erythritol, mannitol and Cr-EDTA) demonstrates a very sharp decrease in permeability as molecular size increases. The membrane behaves like a tight epithelium, with pores of of an approximate radius of 0.45 nm which allow but a poor passive diffusion. On the contrary, permeability to 3 methylglucose and 2 deoxyglucose is much too high for passive diffusion. Transfer competition between D-glucose and 3 methylglucose affords other evidence for a stereospecific monosaccharide carrier. The relationship between the presumably "active" sodium flux out of the fetus and the electrical potential difference across the placenta is discussed. The fetus is usually negative to the mother but the potential difference changes from day to day, and in twin gestation, the respective fetomaternal potentials seem to be independent. Acid infusion to the fetus increases the potential difference. The maintenance of this electrical or chemical gradients is taken as a consequence of the low passive permeability of the placenta.

Animals↗

The genetic structure of a tribal population, the Yanomama Indians. XIV. Clines and their interpretation.

The Yanomama Indians are a South American tribe distributed over an irregular area approximately 200 X 300 miles. The gene frequencies observed at 12 loci in 47 villages within this area have been analyzed for the occurrence of clines. Apparently significant clines are observed for alleles of the Rh, MNSs, Kidd, Gm, Inv and serum albumin system. Available data concerning recent tribal expansion and admixture permit a tentative analysis of the causes of these clines. Although the action of selection cannot be rigorously excluded, it seems unlikely to be the major couse. Admixture with surrounding tribes plays a role which can be quantified because of the fortuitous cicumstance of two genetic markers for admixture. It is suggested that an important factor in the origin of these clines is the manner in which the tribe has recently expanded through successive village fissionings and a predominantly centrifugal pattern of village migration.

Alleles↗

Alpha-fetoprotein levels in maternal plasma and amniotic fluid during prostaglandin-induced mid-trimester abortions: the relation to fetal distress and death.

Alpha-fetoprotein (AFP) levels were measured in both plasma and amniotic fluid during 43 abortions induced with prostaglandin F2alpha (PGF2alpha) and their relationship to the induction-abortion interval and signs of fetal distress or intrauterine death examined. The mean plasma AFP levels showed a progressive rise after PGF2alpha administration but abnormally high levels were found infrequently until the time of delivery. Feto-maternal bleeding could explain the abnormally high plasma AFP levels which occurred early in a few cases. A shorter induction-abortion interval was found in patients with normal plasma AFP levels. Neither fetal distress nor intrauterine death were associated with abnormally high plasma AFP levels. No change in AFP levels in amniotic fluid was found.

Abortion, Induced↗

The genetic structure of a tribal population, the Yanomama Indians XI. Gene frequencies for 10 blood groups and the ABH-Le secretor traits in the Yanomama and their neighbors; the uniqueness of the tribe.

In this paper we present the results of blood group typings for a total of 33 villages distributed among five South American Indian tribes--Yanomama (21 villages), Makiritare (eight villages), Macushi (two villages), Piaroa (one village), and Wapishana (one village). These new results for the Yanomama and Makiritare tribes have been combined with those previously reported to allow a better appreciation of the distribution of allelic frequencies in the tribes. The relationship of the Yanomama to other South American Indian tribes is investigated using data on six polymorphic loci (Rh, MNS, Fy, Jk, Di, Hp). By use of four genetic measures (two of genetic relationship and two of genetic diversity), we demonstrate that the Yanomama are genetically unique among a sample of 20 South American tribes. In addition, the Yanomama show somewhat less genetic diversity for the six loci analyzed than the average South American tribe. Taken together, these results indicate a rather long period of isolation for the population antecedent to the Yanomama--perhaps since the time of entry of man into the South American continent. The pattern of genetic relationships and genetic diversity for the 20 tribes is consistent with the hypothesis that evolution in South America proceeded by a process of fission-fusion leading to isolation of subpopulations with subsequent genetic differentiation as a consequence of population isolation. The uniqueness of the Yanomama appears to stem entirely from such a process, there being no evidence of any selective differential for the loci analyzed.

ABO Blood-Group System↗

Placental lactogen levels in rhesus isoimmunization.

A prospective study of the plasma levels of human placental lactogen (HPL) in pregnancies complicated by rhesus isoimmunization showed that in mild and moderately affected cases the levels were normal, while in severely affected cases they were raised. Serial levels of HPL before the 26th week provide a valuable indication of fetal outcome, and we suggest that this estimation should be used routinely as an adjunct to other tests in the management of rhesus isoimmunization.

Antibody Formation↗