Biomedical subjects
E M Symonds
Publications and source records attributed to E M Symonds.
Cumulative changes in the fetal electrocardiogram and biochemical indices of fetal hypoxia.
Previous studies have shown that the relationship between P-R interval of the fetal electrocardiogram (FECG) and the fetal heart rate (FHR) varies according to the acid-base status of the fetus. In the normal fetus there is a negative correlation between these two parameters. However, as acidosis develops, the relationship becomes positive. In order to express this relationship in a quantitative form, an index known as the ratio index (RI) has been derived. This index provides a cumulative time based description of the relationship between the P-R interval and FHR for the whole labour. The aim of this study was to evaluate this derived index and compare it with fetal hypoxia. The FECG was recorded from 132 fetuses during labour using a fetal scalp electrode, and analysed using the Nottingham FECG system. Changes in the nature of this relationship between the P-R interval and heart rate were compared against biochemical markers of asphyxia, namely umbilical artery pH, lactate and umbilical venous norepinephrine and hypoxanthine. Significant correlations were demonstrated between the RI and umbilical arterial pH (r = -0.38, P < 0.01), lactate (r = 0.36, P < 0.01), log10norepinephrine (r = 0.37, P < 0.01), and hypoxanthine (r = 0.28, P < 0.01). The measurement of the ratio index during labour may be a useful method of determining fetal hypoxia during labour.
Plymouth randomized control trial of cardiotocogram only versus ST waveform plus cardiotocogram for intrapartum monitoring in 2400 cases.
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Neonatal platelet reactivity and serum thromboxane B2 production in whole blood: the effect of maternal low dose aspirin.
OBJECTIVES: Concern has been expressed about possible neonatal side effects after the use of maternal anti-platelet agents in pregnancy, particularly low dose aspirin treatment. We have studied neonatal platelet behaviour using whole blood techniques, and assessed the neonatal effect of the maternal ingestion of 60 mg aspirin daily. DESIGN: Cross sectional and randomised, double-blind, placebo-controlled. SETTING: University hospital. SUBJECTS: 1. Eight normal women, studied before conception, and their infants. 2. Twenty-four infants whose mothers had been randomised to receive either 60 mg aspirin daily, or placebo, in double-blind fashion. METHODS: The Clay Adams Ultra Flo 100 whole blood single platelet counter was employed to measure platelet aggregation in response to various agonists. The platelet release reaction was also measured in whole blood, and serum thromboxane B2 (TxB2) production was measured by radio-immunoassay. Umbilical cord blood samples were obtained at delivery. RESULTS: 1. Neonatal platelet aggregation induced by adrenaline, ADP and platelet activating factor was reduced in comparison with their mothers (P < 0.01), whereas the neonatal platelet release reaction was reduced when stimulated by collagen and U46619 (a thromboxane mimetic) (P < 0.01). Serum TxB2 production was similar in mothers and babies. 2. Neonatal platelet aggregation, release reaction and serum TxB2 production were not significantly reduced in infants exposed to maternal aspirin in comparison with those neonates exposed to maternal placebo. This is in contrast to the effect on maternal platelets. CONCLUSIONS: Although only a small number of patients were studied, we interpret this as a relative sparing of neonatal platelet reactivity due to the presystemic action of low dose aspirin.
Neonatal and maternal platelet cytosolic calcium in normotensive and hypertensive pregnancies.
A prospective study investigated platelet cytosolic calcium in non-pregnant volunteers (n = 30) and samples from the umbilical veins of babies from both normotensive (n = 18) and hypertensive (n = 15) primigravidae, and their mothers. There was no significant difference between the neonatal umbilical venous platelet cytosolic calcium concentration (p[Ca2+]i) in babies born to normotensive primigravidae or to those whose pregnancies were complicated by gestational hypertension (88 x 9 (SE) 2 x 5) in normotensive primagravidae, 80 x 6 (2 x 8) in pregnancy induced hypertension without proteinuria, and 89 x 3 (3 x 2) nmol/l in pre-eclampsia. There was also no significant difference in the p[Ca2+]i from the umbilical veins of the pregnancies studied and those of non-pregnant female volunteers in the follicular phase of their menstrual cycle. This was despite a gradual and significant rise in p[Ca2+]i with increasing severity of disease in the mothers of the babies studied (119 x 9 (4 x 1) in normotensive primagravidae, 130 x 8 (7 x 3) in pregnancy induced hypertension without proteinuria, and 148 x 2 (4 x 5 ) nmol/l in pre-eclampsia). The mean maternal p[Ca2+]i in the three samples returned to concentrations comparable with those in non-pregnant subjects by 12 weeks after birth. These data demonstrate no significant difference between the mean p[Ca2+]i in non-pregnant women and those obtained from the umbilical venous blood of normotensive or hypertensive primigravidae. They suggest that the functional hypoactivity of neonatal platelets is probably not secondary to a decrease in basal p[Ca2+]i. They also suggest that the progressively raised p[Ca2+]i in normal and hypertensive pregnancies might be due to a pregnancy specific factor that does not cross the placenta,
Fetal monitoring: medical and legal implications for the practitioner.
Seventy per cent of all claims concerning intrapartum care in relation to fetal brain damage are based on abnormalities of the cardiotocograms and electronic fetal monitoring. Claims arise because of failure to take action in the presence of an abnormal cardiotocogram, or because of delayed response to an abnormal tracing. Difficulties in court arise from variations in the interpretation of the significance of recordings. The importance of taking appropriate action in the presence of an abnormal cardiotocogram, and in keeping accurate time-sensitive records is emphasized.
Platelet cytosolic calcium in human pregnancy complicated by essential hypertension.
Five pregnant women whose pregnancies were complicated only by essential hypertension had significantly elevated platelet cytosolic calcium levels as compared with those of their normotensive counterparts. There seems to be an association between platelet cytosolic calcium level and arterial blood pressure that has previously been described in both nonpregnant and preeclamptic women.
Immunoscintigraphy of ovarian carcinoma using a monoclonal antibody (111In-NCRC48) defining a polymorphic epithelial mucin (PEM) epitope.
An anti-polymorphic epithelial mucin (PEM) monoclonal antibody NCRC48 (IgG3) has been tested for its capacity to localize in tumours according to accepted guidelines for human administration. Following radiolabelling with 111In, 1 mg antibody was administered to 19 patients with a clinical suspicion of ovarian malignancy. Initial imaging and biodistribution studies confirm the safety of this conjugate although six out of 11 patients tested developed an antibody response to the monoclonal antibody. Immunoscintigraphy with this antibody was compared with magnetic resonance imaging and ultrasound in relation to the final tumour histology, the final accuracies being 79, 79 and 64% respectively. Positive localization of antibody was confirmed in malignant tissue with little evidence of uptake in benign tissue.
Litigation and the cardiotocogram.
The extent of the liability in obstetric litigation is discussed. Arguments between experts reveal the lack of agreed standards in cardiotocography. This paper discusses the problems which need to be addressed when defining what constitutes an abnormal cardiotocogram (CTG), how long it needs to abnormal before it is significant, the contribution made by inadequate equipment and the question of whether it is defensible to decide positively not to monitor. Records need to be archived for a minimum of 25 years.
Changes in platelet intracellular free calcium in normal pregnancy.
OBJECTIVE: To determine if platelet intracellular free calcium concentration (p.(Ca2+)i) changes with gestation in normotensive, uncomplicated pregnancy. DESIGN: A prospective, longitudinal study of primigravid pregnant women compared to a large control group consisting of nulliparous nonpregnant volunteers. SETTING: The antenatal clinic at University Hospital, Queen's Medical Centre, Nottingham. SUBJECTS: Two groups of women were studied. Thirty-one nulliparous, nonpregnant women not using oral contraception were investigated in the early follicular phase of their menstrual cycles. Also, 24 primigravid women with normotensive, uncomplicated pregnancies were investigated on eight separate occasions during their pregnancies. RESULTS: A significant increase in mean p.(Ca2+)i was demonstrated by 28 weeks gestation in the pregnant women as compared to the nonpregnant control group and the same individuals when investigated at 12 weeks postpartum (P < 0.05; ANOVA). This change was maximal at 36 weeks gestation (P < 0.001; ANOVA); concentrations had returned to those not significantly different from nonpregnant women by six weeks postpartum. CONCLUSIONS: Basal platelet (Ca2+)i increases significantly by the third trimester of normal, primigravid pregnancy as compared to pregnancy values and postnatal values. These data mirror the previously described observations of platelet behaviour noting increased activity at this gestation of pregnancy. It may be that the increased basal p.(Ca2+)i indicates that smaller transient signals have to be generated to induce platelet activity, such as shape change, aggregation and exocytosis.
Customised antenatal growth charts.
Charts for fetal growth do not take physiological variables into account. We have therefore designed a computer-generated antenatal chart that can be easily "customised" for each individual pregnancy, taking the mother's characteristics and birthweights from previous pregnancies into consideration. The adjusted birthweight range expected at 40 weeks' gestation is combined with a standard, longitudinal ultrasound-derived curve for intrauterine weight gain. Review at the Queen's Medical Centre, Nottingham, UK, of 4179 pregnancies with ultrasound-confirmed dates showed that, in addition to gestation and sex, maternal weight at first antenatal-clinic visit, height, ethnic group, and parity were significant determinants of birthweight in our population. Correction factors were calculated for each of these variables and entered into a computer program to adjust the normal birthweight centile limits. With adjusted centiles we found that 28% of babies conventionally designated small for gestational age (less than 10th centile) and 22% of those designated large (greater than 90th centile) were in fact within normal limits for the pregnancy. Conversely, 24% and 26% of babies identified as small or large, respectively, with adjusted centiles were "missed" by conventional unadjusted centile assessment. Adjustment for physiological variables will make assessment of fetal growth more precise and reduce unnecessary investigations, interventions, and parental anxiety.
The resolution of chronic pelvic pain after normal laparoscopy findings.
Sixty patients with chronic pelvic pain were monitored after diagnostic laparoscopy had excluded obvious pelvic pathology. Six months after the procedure only two patients described their symptoms as unchanged or worse. Treatment should be limited to the minority of patients whose symptoms remain 6 months after laparoscopy.
Changes in human platelet angiotensin II binding sites associated with early pregnancy.
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Longitudinal study of platelet angiotensin II binding in human pregnancy.
1. Platelet angiotensin II binding, circulating angiotensin II levels, plasma renin substrate and plasma renin concentration were measured in a longitudinal study of 30 women during pregnancy and the puerperium. 2. There was a significant fall in platelet angiotensin II binding from 11 weeks gestation to 18 weeks gestation (P less than 0.01). There were no further significant changes in platelet angiotensin II binding until after delivery, a significant rise in platelet angiotensin II binding being found at 6 weeks post partum as compared with at 36 weeks gestation (P less than 0.01). There was no further significant change from 6 to 12 weeks post partum, and platelet angiotensin II binding at 6 and 12 weeks post partum in the pregnant cohort approximated to that in nonpregnant women. These changes parallel those known to occur in pressor responsiveness to angiotensin II in pregnancy. 3. Plasma angiotensin II concentration, plasma renin substrate and plasma renin concentration were all significantly higher during pregnancy than in the puerperium (P less than 0.001). There were no significant changes during pregnancy in plasma angiotensin II concentration or plasma renin concentration, although plasma renin substrate rose throughout. 4. Significant inverse correlations between platelet angiotensin II binding and plasma angiotensin II concentration (P less than 0.01), plasma renin substrate (P less than 0.01) and plasma renin concentration (P less than 0 greater than 001) were found during pregnancy. These data suggest that down-regulation of platelet angiotensin II binding by the components of the renin-angiotensin system pertains in pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparative study of platelet angiotensin II binding and the angiotensin II sensitivity test as predictors of pregnancy-induced hypertension.
1. Platelet angiotensin II binding was measured in 34 primigravid women (between 28 and 32 weeks gestation), in whom the pressor response to infused angiotensin II was also determined. 2. There was a significant correlation between the platelet angiotensin II binding and the slope of the curve relating the diastolic pressor response to infused angiotensin II (P less than 0.01), suggesting that co-linearity between the two techniques exists and supporting the use of platelet angiotensin II binding as a model of vascular smooth muscle pressor responsiveness. 3. Ten of the 34 women subsequently developed pregnancy-induced hypertension. Platelet angiotensin II binding in the patients who subsequently developed pregnancy-induced hypertension was sixfold higher than in the patients who remained normotensive (P less than 0.001). There were, however, no significant differences between the groups in any of the parameters derived from the angiotensin II infusion experiments. 4. The use of platelet angiotensin II binding alone in predicting the outcome of the pregnancies, as assessed using discriminant analysis, was more successful than when any of the infusion parameters were used, with 77% of patients being correctly classified.
A randomised placebo controlled trial of labetalol in the treatment of mild to moderate pregnancy induced hypertension.
OBJECTIVE: To determine the need for, and efficacy of, treatment with labetalol in women with mild-to-moderate pregnancy induced hypertension (PIH). DESIGN: Prospective double-blind randomised placebo controlled study. SETTING: Maternity units of five hospitals in the Trent Region. SUBJECTS: 144 women (86 primigravid) who developed PIH after 20 weeks gestation. INTERVENTIONS: Treatment with oral labetalol up to 600 mg daily or placebo with subsequent care of treatment failures in accordance with the attending obstetrician's practice. MAIN OUTCOME MEASURES: Number of days spent as an antenatal inpatient; the development of proteinuria; the perceived need for induction of labour or elective caesarean section; and gestation age at delivery. RESULTS: Labetalol significantly lowered the blood pressure and reduced the incidence of proteinuria. However, neither the number of days spent as an antenatal inpatient, nor the perceived need for induction of delivery or elective caesarean section, nor the gestation age at delivery differed significantly between the two treatment groups. Post-randomisation consideration of early (< or = 32 weeks) and late (> 32 weeks) onset groups showed the placebo treated early-onset group (n = 15) to have more patients with severe hypertension (> 150/110 mmHg) and a greater requirement for additional antihypertensive therapy prior to labour than the group treated with labetalol (n = 16). CONCLUSION: Anti-hypertensive intervention therapy in pregnancy induced hypertension has been examined using a placebo controlled randomised double-blind trial of labetalol in pregnancy. The maximum blood pressure prior to labour and the incidence of proteinuria was reduced in women on active therapy. However, the length of gestation was not significantly prolonged and indices of clinical outcome were not significantly altered. The appropriateness of pharmacological therapy for late-onset PIH may be questioned.
A randomized placebo-controlled study of the effect of low dose aspirin on platelet reactivity and serum thromboxane B2 production in non-pregnant women, in normal pregnancy, and in gestational hypertension.
OBJECTIVE: To investigate the effect of 60 mg aspirin daily on platelet reactivity and prostaglandin production in various groups of patients. Similar regimens, which are thought to act through inhibition of platelet thromboxane production, are currently undergoing clinical assessment for the prevention of pre-eclampsia and intrauterine growth retardation. DESIGN: A prospective randomized placebo controlled study. SETTING: University Hospital, Nottingham. SUBJECTS: 12 non-pregnant female volunteers, 18 normal primigravidae before 16 weeks gestation and 16 pregnant women admitted with gestational hypertension (GH) at a mean gestation of 38 weeks. INTERVENTIONS: In the non-pregnant women blood samples were taken before and after a 10-day course of 60 mg aspirin daily. The primigravidae had blood samples taken at 16 weeks and then they were randomized to receive either 60 mg aspirin daily or a matched placebo. Further blood samples were obtained at 28, 32 and 36 weeks. MAIN OUTCOME MEASURES: Changes in platelet reactivity and release reaction, and serum thromboxane production, were estimated in whole blood. RESULTS: 60 mg aspirin daily significantly inhibited cyclo-oxygenase dependent platelet aggregation, release reaction and serum thromboxane production in non-pregnant and pregnant women, and in women with GH (P less than 0.01). When adrenaline was used as the aggregating agent, the cyclo-oxygenase pathway was recruited in the increased reactivity seen in the third trimester of normal pregnancy, and was sensitive to inhibition by low dose aspirin. CONCLUSION: Low dose aspirin would appear to be an appropriate agent for the inhibition of platelet reactivity associated with hypertensive pregnancy.