P. Donnai

Amino acid (system A) transporter activity in microvillous membrane vesicles from the placentas of appropriate and small for gestational age babies

ABSTRACT: Although a number of causes of poor fetal growth are known, the involvement of placental transport proteins in the etiology of growth retardation is not understood. The aim of this study was to investigate the activity of the system A amino acid transporter and the Na+/H+ exchanger in vesicles isolated from the microvillous membrane of the syncytiotrophoblast of placentas of appropriate and small for gestational age babies. There were no biochemical differences between the membranes from the two groups of placentas, and there was no difference in the activity of the Na+/H+ exchanger. The initial rate of uptake of methylaminoisobutyric acid (a nonmetabolizable amino acid analogue) was 63% lower in vesicles from placentas of small for gestational age babies. Kinetic analysis of the system A transporter (utilized by methylaminoisobutyric acid) showed that the Vmax in the vesicles from placentas of small for gestational age babies (0.24 ± 0.03 nmol/mg protein/30 s, n = 5) was significantly lower than that in vesicles from placentas of appropriate for gestational age babies (0.64 ± 0.09 nmol/mg protein/30 s, n = 4, p < 0.001), whereas the Km was not different between the two groups. It is concluded that there is an abnormality of system A amino acid transporter function in placentas of small for gestational age babies.

Outcome of pregnancy in women with Marfan's syndrome

Objective To improve life expectancy and prevent premature mortality in women with Marfans syndrome.

Antenatal administration of betamethasone to prevent respiratory distress syndrome in preterm infants: report of a UK multicentre trial

In a prospective, randomized, double‐blind, multicentre trial the effect of antenatal treatment with betamethasone phosphate was compared with placebo in the prevention of the respiratory distress syndrome (RDS) in preterm infants. The dose of betamethasone was 4 mg every 8 h for six doses, unless delivery occurred. The 251 women who were enrolled gave birth to 262 liveborn infants, 130 in the betamethasone and 132 in the placebo group; the two groups were evenly matched in most respects. The diagnosis of RDS in the newborn was confirmed by two independent assessors. Seven of the 130 infants in the betamethasone group and 16 of the 132 in the placebo group developed RDS. In infants whose mothers had received at least three injections, RDS was also less frequent in the steroid group than in the placebo group (3/104 and 10/104 respectively; P<0·05). There was a significant reduction of RDS in those born between 24 h and 6 days after entry into the trial (0/30 and 8/45 respectively; P<0·05). The largest difference in frequency of RDS occurred in the subgroup of infants born before 34 weeks gestation, within 8 days of trial entry, and whose mothers had received at least three injections (0/27 steroid group and 7/32 placebo group; P=0·03), and there were also significantly fewer neonatal deaths (2/27 and 13/32, respectively; P<0·01) in this subgroup. Betamethasone did not provoke earlier delivery. Premature rupture of the membranes and maternal hypertension did not seem to contraindicate the use of steroids: there was no increase in maternal or neonatal sepsis nor in stillbirth in hypertensive pregnancies in the steroid group. Neonatal jaundice was significantly less frequent in the steroid (55/129) than in the placebo group (81/127; P<0·01) but not in the subgroups born before 34 completed weeks gestation.

PLASMA NORADRENALINE IN NORMAL PREGNANCY AND IN HYPERTENSION OF LATE PREGNANCY

Plasma noradrenaline was measured by radioenzymatic assay on 90 occasions in 72 women throughout normal pregnancy. Plasma noradrenaline levels declined as pregnancy advanced. A total of 21 patients who developed hypertension in late pregnancy were found to have plasma noradrenaline levels significantly lower than controls at the same stage of pregnancy. It is concluded that plasma noradrenaline is reduced in hypertension of late pregnancy. This indicates a compensatory reduction in sympathetic nervous system activity.

Importance of vitamin C in maintenance of the normal amnion: An experimental study

Collagenous matrix in amnion accounts for most of the dry weight of the tissue and provides its mechanical strength and resistance to rupture. Cell and organ culture techniques have been utilized to study the influence of vitamin C upon the synthesis and deposition of extracellular matrix by cells of normal amnion at term. The cultures have been examined using light and electron microscopy and metabolic labelling. These studies show that both epithelial cells and fibroblasts of the deeper stromal layer are active in the production of fibrillar matrix at this time. Matrix deposition by epithelial cells in culture increases several-fold when the vitamin C concentration in the supernatant medium is increased from zero to 50 micrograms/ml, and, at the latter concentration, a continuous anastomosing fibrillar collagenous meshwork appears beneath the cells. This study thus provides new evidence that an adequate dietary supply of vitamin C is probably needed to maintain the strength of the chorioamnion.

Risk-reducing surgery for ovarian cancer: outcomes in 300 surgeries suggest a low peritoneal primary risk.

Risk-reducing salpingo-oophorectomy is currently advocated for the reduction of both breast and ovarian cancer risk in BRCA1/2 carriers, but residual risk of peritoneal primary cancer remains a concern. A sequential series of women attending a single institution for ovarian risk management underwent either risk-reducing surgery or screening. A person-years at risk analysis was used to compare observed versus expected cancers. In total, 300 women underwent risk-reducing salpingo-oophorectomy, including 160 BRCA1/2 mutation carriers. Three occult ovarian cancers were detected at surgery. There have been 2400.4 years of follow-up and 15.79 expected cancers. No peritoneal cancers have occurred. Amongst 503 women controls with 3444.3 years of follow-up, 15.93 ovarian cancers were expected and 17 were found. There were six ovarian cancer-related deaths in the control group compared with one in the surgery group. Risk-reducing salpingo-oophorectomy in a single institution has so far avoided peritoneal cancer incidence.

Human amniotic fluid urogastrone (epidermal growth factor) and fetal lung phospholipids

Summary. Urogastrone was measured by radioimmunoassay in amniotic fluid obtained from 186 complicated pregnancies at 22 to 40 weeks gestation. Amniocentesis was performed for a variety of indications to obtain information about fetal lung maturity or bilirubin levels before induction of labour or caesarean section in various obstetric conditions. In 114 specimens lung phospholipids extracted from amniotic fluid were also assayed using two‐dimensional thin layer chromatography. Urogastrone concentrations became measurable at approximately 30 weeks gestation and thereafter there was a 10‐fold rise in concentrations between 30 and 40 weeks gestation. This increase in urogastrone concentration was positively correlated with a rise in phosphatidylcholine and phosphatidylglycerol concentrations and the phosphatidylcholine (lecithin)/sphingomyelin ratio (L/S). These results are compatible with a role for urogastrone in human fetal lung maturation.

Fetal and maternal blood volumes in shed human placentae: discrepant results comparing morphometry to haemoglobin content.

The maternal blood volume (MBV) and fetal blood volume (FBV) of shed human placentae delivered by caesarean section at term were measured using a morphometric technique and from the placental content of adult and fetal haemoglobin. MBV was 35.3 +/- 1.5 (s.e.m.) per cent by the former and 11.0 +/- 1.5 per cent by the latter technique. FBV was 11.0 +/- 0.7 and 9.0 +/- 0.6 per cent respectively (n = 6). Measurement of the dimensions of individual villi initially photomicrographed in 0.9 per cent NaCl and subsequently re-photographed in fixative suggested that individual villi shrank to 0.7 of their initial volume during fixation. It is suggested that morphometric measurement of MBV may lead to approximately a threefold overestimate because of relative MBV expansion and villous tissue shrinkage during the process of fixation without alteration in overall placental volume.

COMPARISON OF PREGNANCY OUTCOME AFTER AMNIOCENTESIS FOR PREVIOUS NEURAL TUBE DEFECT OR RAISED MATERNAL SERUM ALPHAFETOPROTEIN

Amniocentesis was performed in 219 pregnancies because a previous pregnancy produced a fetus with neural tube defect (NTD) and in 212 pregnancies in which the indication for amniocentesis was a high maternal serum alphafetoprotein (AFP) level. The proportion of abnormal fetuses, the frequency of low birth weight infants, and the frequency of undesired fetal loss were significantly greater in the group with high maternal serum AFP, in which there was also a significant excess of male births. It is concluded that maternal serum AFP screening defines a group of high risk pregnancies. The greater fetal loss and low birth weight associated with high maternal serum AFP levels were not the result of amniocentesis but were an inherent feature of these pregnancies.

AMNIOTIC FLUID OPTICAL DENSITY DETERMINATION AS A RAPID TEST FOR ASSESSMENT OF FETAL LUNG MATURITY

The lecithin/sphingomyelin (L/S) ratios and optical densities at 650 nm were determined for 158 samples of amniotic fluid obtained by amniocentesis. A further 24 samples collected by vaginal aspiration from patients with spontaneous rupture of the membranes were also analysed. The relation between the L/S ratio and the optical density suggests that the more rapidly obtainable optical density measurement could be used as a screening procedure for fetal pulmonary maturity. A valid estimate of maturity by optical density is not possible in amniotic fluid aspirated from the vagina.