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The objective of the study is to determine the proportion and different types of birth defects among the children born in Hospital Kuala Lumpur. A cross-sectional study was conducted for a period of 18 months where all consecutively born infants, dead or alive were included. There were total of 34,109 births recorded during this period. The proportion of birth defects in Hospital Kuala Lumpur was 3.1% (n = 1056). The commonest involved were the hematology system, (157.7 per 10,000 births), the central nervous system, genitourinary system and chromosomal anomalies. The proportion was significantly higher in males and in the Chinese (p < 0.001). The commonest abnormalities are Glucose 6 Phosphate Deficiency (157.7/10000), Down's syndrome (12.6/10000), thalassaemia (8.8/10000), cleft lip and/or palate (7.6/10000) and anencephaly (7.3/10000). Neural tube defect is common and ranked second after G6PD deficiency. There is a need for a birth defect registry to assess the extent of the problem in Malaysia.

This study reviews the deliveries of macrosomic babies and their outcomes. A total of 330 macrosomic (birth weight > or =4 kg) cases were studied retrospectively from July 1999 to December 1999 in the Maternity Hospital of Kuala Lumpur. The variables studied included induction of labour, mode of delivery and the incidence of maternal and perinatal complications. Three hundred and thirty macrosomic infants were delivered during the period of study. Vaginal delivery was achived in 56% of the study cases. The percentage of vaginal delivery was higher among those who had induction of labour (63%) compared to the group without induction of labour (50%). Vaginal delivery was planned in 267 mothers and of these 69% achieved vaginal delivery. Twelve per cent of the macrosomic infants were delivered by elective caesarean section. Shoulder dystocia occurred in 4.9% of vaginal deliveries. Eighty-eight neonates were admitted to the special care nursery unit and 57% of these infants were delivered by elective caesarean section. Perineal trauma occurred in 26% of vaginal deliveries. Post-partum haemorrhage occurred in 32% of caesarean deliveries compared to 4% in vaginal deliveries. Two cases of stillbirths were documented but no maternal death occurred during the period of study. Vaginal delivery is the most frequent mode of delivery for a fetus weighing in excess of 4 kg and vaginal delivery should be attempted in the absence of contraindications, because vaginal delivery has less maternal morbidity compared to caesarean delivery. However, shoulder dystocia remains a significant complication of vaginal delivery for macrosomic fetuses.

Objective: To assess the safety and targeting ability of the engineered human antibody (hCTMO1) in women with ovarian carcinoma., Design: The monoclonal antibody labelled with Indium-111 was administered to women with suspected primary or recurrent ovarian carcinoma six days pre-operatively. The first group of women was given a dose of 0.1 mg per kg body weight of radiolabelled antibody. A second group of women received 1 mg per kg body weight and finally a third group was given 1 mg per kg body weight of unlabelled antibody followed one hour later by 0.1 mg per kg body weight of radiolabelled antibody. All the women were then imaged using a gamma camera one hour and up to 96 hours after injection., Participants: Fourty-four women in whom there was a high suspicion of primary ovarian carcinoma on the basis of ultrasound or CT imaging and serum CA125 and those in whom there was a suspicion of recurrent ovarian carcinoma after being treated for histologically confirmed carcinoma., Setting: The Queen's Medical Centre, Nottingham and University Hospital Vrije Universiteit, Amsterdam, The Netherlands., Results: At the low dose of antibody the sensitivity for detection of ovarian carcinoma was 70%. After increasing the dose of antibody and also after pre-dosing with unlabelled antibody the sensitivity increased to 100%, but there was a large number of false positive results at the higher dose, and therefore the specificity was low. The liver and bone marrow were the organs with the highest activities., Conclusion: The genetically engineered antibody hCTMO1 is safe for use in women. This antibody effectively targets ovarian carcinoma and has greater potential as a vector for therapeutic use than as a diagnostic agent.

Objective: To determine the incidence of cellular proliferation in the placenta throughout the three trimesters of normal pregnancy, and in the third trimester of pregnancy complicated by intrauterine growth restriction (IUGR)., Methods: Placental samples were obtained from 17 first-trimester pregnancies, 9 second-trimester pregnancies, 33 uncomplicated third-trimester pregnancies, and 21 third-trimester pregnancies complicated by IUGR. These samples were then stained by immunohistochemical technique, using the monoclonal antibody MIB-1., Results: The incidences of cellular proliferation in the four groups were as follows: first trimester (n = 17): 11.8% of cells (8.51-17.04); second trimester (n = 9): 9.88% of cells (5.04-10.99); normal third trimester (n = 33): 3.15% of cells (2.07-3.7); IUGR third trimester (n = 21): 3.7% of cells (3.02-4.85). The decline in cellular proliferation throughout the three trimesters of pregnancy was statistically significant (P < .0001 Kruskall-Wallis test). The Spearman rank correlation for proliferative index against gestational age had a P value less than .0001 (Rho corrected for ties = -0.81). There was no statistically significant difference in the incidence of cellular proliferation between normal third-trimester and IUGR third-trimester samples., Conclusion: The incidence of cellular proliferation in the placenta declines as pregnancy progresses, a finding that agrees with previous work by others. The incidence of cellular proliferation was not altered in cases of IUGR.

mAb hCTM01 binds a carcinoma-associated antigen, the MUC1 gene product. The antigen is also present in the circulation, and administration of 111In-labelled hCTM01 results in the formation of immune complexes with enhanced accumulation in the liver. To avoid the unwanted effect of circulating radioactive immune complexes, a strategy to remove the circulating antigen was investigated using a split-dosage schedule. Eleven patients suspected of having ovarian carcinoma were injected with 1 mg/kg unlabelled hCTM01, 1 h before receiving 0.1 mg/kg 111In-labelled hCTM01 (100 M Bq). The amount of radioactivity was determined in resected tumour tissue, various normal tissues and blood samples obtained at laparotomy 6 days postinjection (p.i.). In all patients, the circulating antigen decreased to its nadir after the unlabelled antibody infusion and immune complex formation was demonstrated. Uptake in tumour deposits 6 days p.i. was 11.1 times higher than in normal tissues (P < 0.0001) and 5.9 times higher than in blood (P < 0.0001). 111In activity in liver tissue was comparable to 111In uptake in tumour tissue, and considerably lower than previously reported in patients not pretreated with unlabelled antibody. The split-dosing strategy would appear to be advantageous for use of hCTM01 as a specific carrier for the delivery of cytotoxic agents to patients with ovarian cancer.

Objectives: Our purpose was to investigate a possible role for apoptosis in the pathophysiologic mechanisms of intrauterine growth restriction., Study Design: Placental samples were obtained from 43 uncomplicated third-trimester pregnancies and from 26 pregnancies complicated by intrauterine growth restriction. The definition used to identify cases of intrauterine growth restriction depended on three criteria: clinical evidence of suboptimal growth, ultrasonographic evidence of deviation from an appropriate growth percentile, and individualized birth weight ratios <10th percentile. Light microscopy was used to quantify the incidence of apoptosis. Electron microscopy and TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) staining were used to confirm the occurrence of apoptosis., Results: Quantification of apoptosis (medians and interquartile ranges) resulted in the following values: normal third trimester (n = 43) 0.14% of cells (0.08% to 0.20%) and intrauterine growth restriction third trimester (n = 26) 0.24% of cells (0.16% to 0.29%). The incidence of apoptosis was significantly higher in placentas from pregnancies with intrauterine growth restriction compared with normal third-trimester placentas (p < 0.01, Mann Whitney U test)., Conclusions: These results suggest that apoptosis may play a role in the pathophysiologic mechanisms of intrauterine growth restriction.

Objectives: The study aims were to conclusively demonstrate apoptosis in the human placenta and to quantify its incidence at different stages of pregnancy., Study Design: Placental samples were obtained from 28 first-trimester pregnancies and 38 uncomplicated third-trimester pregnancies. Light microscopy, electron microscopy, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate marker nick end-labeling staining were used to identify apoptosis. Light microscopy was used to quantify its incidence., Results: Apoptosis has been conclusively demonstrated within placental tissue. Quantification of apoptosis (medians and interquartile ranges) was as follows: first trimester (n = 28), 0.07% of cells (0.05% to 0.14%); third trimester (n = 39), 0.14% of cells (0.09% to 0.20%). The incidence of apoptosis was significantly higher in the third trimester than in the first trimester (p < 0.01, Mann-Whitney U test)., Conclusions: Placental apoptosis increases significantly as pregnancy progresses, suggesting that it may play a role in the normal development and aging of the placenta.

Clinical studies are currently underway to assess the biodistribution and therapeutic potential of the genetically engineered human antibody hCTM01 directed against polymorphic epithelial mucin (PEM) in patients with ovarian carcinoma. The present study was undertaken to assess the effect of circulating PEM antigen on the biodistribution of the anti-PEM antibody in mice bearing MUC-1 transfected adenocarcinoma cell lines. Tumour xenografts were established from three cell lines: 413-BCR, which expressed antigen on the cell surface and also shed antigen into the circulation, E3P23, which expressed the antigen but did not shed into the circulation, and a negative control (410.4 MUCI). Groups of five mice were injected with 1.0 mg/kg antibody, imaged after 72 h and then sacrificed, followed by assay of tissue uptake. The results showed a clear difference in the tumour and liver uptake, with the non-secreting cell line showing almost twice the tumour uptake and approximately 20% of the liver uptake of the secreting cell line.

Thirty-one patients suspected of having ovarian cancer received a single i.v. injection of radiolabeled (100 MBq (111)In) engineered human CTMO1 (hCTMO1) to investigate its potential as an internalizing drug carrier. hCTMO1 is a complementary-determining region-grafted human IgG4 monoclonal antibody recognizing an ovarian carcinoma-associated antigen, the MUC-1-gene product. The amount of radioactivity was determined in tumor tissue, various normal tissues, including liver biopsies, and blood samples obtained at laparotomy, 6 days after injection of either 0.1 or 1.0 mg hCTMO1/kg of body weight. Circulating antigen-15-3 was measurable in all patients before injection, and immune complex formation was already present at the end of infusion. In the 0.1 mg/kg group, most of the radioactivity was bound to immune complexes, whereas in the 1.0 mg/kg group, most was bound to IgG monomers. Increasing the hCTMO1 dose 10-fold did not influence the overall disappearance of (111)In from the blood, but the elimination half-life of (111)indium bound to immune complexes was increased 2-fold. Uptake in tumor tissue 6 days postinjection at the 0.1 mg/kg dose was 7.6 times higher (P = 0.0009) than in normal tissue and 2.5 times higher (P = 0.03) than in blood. At the 1.0 mg/kg dose, the uptake in tumor tissue was 14.0 times higher (P = 0.0003) than in normal tissue and 8.1 times higher (P = 0.0007) than in blood. Liver activity was substantial (23.7 +/- 10.5 and 18.3 +/- 6.7% of the injected dose/kg for the 0.1 and 1.0 mg/kg dose group, respectively). These results are superior to those found with other clinically tested anti-MUC-1 gene product antibodies. hCTMO1 seems to be a suitable carrier for cytotoxic agents in ovarian carcinoma patients; the better uptake results and tumor-to-blood ratios are obtained at the higher dose of 1.0 mg hCTMO1/kg body weight.

A retrospective study was performed at the Queens Medical Centre, Nottingham, UK to evaluate the potential value of PR interval analysis of the FECG compared to conventional intrapartum assessment with fetal heart rate monitoring. Two-hundred sixty-five labours were selected for monitoring. Outcome was assessed by the number of fetal scalp blood samples (FBS) performed and the associated incidence of acidosis in the first stage of labour, the mode of delivery and whether or not this was expedited for fetal heart abnormality or an abnormal scalp pH. The condition of the fetus at delivery was assessed by arterial and venous blood acid-base status, Apgar score and the need for admission to the neonatal intensive care unit. Conventional electronic fetal heart rate monitoring (EFM) was used in all labours. The addition of PR interval assessment would potentially reduce the numbers of normal FBSs being carried out from 85.5% to 26.8% and the proportion of cases of missed acidosis at delivery from 8.5% to 4.5%. These results highlight the potential benefit of PR interval analysis in improving interpretation of the intrapartum cardiotocograph and need to be tested by prospective randomised controlled study.

Objectives: The evaluation of the changes in the relationship of the PR interval and fetal heart rate during prolonged fetal compromise in sheep at levels of acidosis comparable to those seen during human fetal compromise and to see whether these changes are potentially of use in the detection of fetal distress., Study Design: A retrospective analysis of continuous fetal electrocardiogram recordings during graded fetal hypoxemia in 20 chronically cannulated fetal sheep was performed. Baseline recordings during normoxemia were compared with recordings during hypoxemia by use of Fisher's exact test and the Student t test., Results: Sixteen of the 20 cases could be used for final analysis. Twelve showed a statistically significant change from a predominantly negative relationship between the PR interval and the fetal heart rate during normoxemia to a predominantly positive relationship during hypoxemia. Two cases showed an obvious trend in the same direction, which was statistically not significant. In two other cases no change in the relationship was observed., Conclusion: A changing relation between the PR interval and the fetal heart rate is of potential use in the detection of fetal compromise.

Advances in microprocessing technology have made fetal ECG analysis a feasible adjunct to fetal surveillance. Time interval and morphology changes of the FECG occur during fetal hypoxia. The use of these changes to detect a fetus at risk of intrapartum asphyxia awaits validation in terms of both future and ongoing clinical trials. Recognition of FECG changes during decelerations may improve the sensitivity of EFM. Antepartum FECG analysis has potential for the detection of a number of pathological fetal conditions, including intrauterine growth retardation, but remains hampered by low signal-to-noise ratios, rendering successful signal acquisition unreliable.

During the past decade a variety of intrapartum fetal monitors have been constructed that process the entire fetal electrocardiogram (FECG), obtained via a scalp electrode. They therefore differ from conventional monitors in aiming to extract relevant timing and magnitude information from the morphology of the FECG rather than simply the RR interval and hence heart rate. An intrapartum monitor such as this has been successfully developed by ourselves. This paper describes the early results obtained whilst attempting to extend this form of monitoring forward into the antenatal period. In order to achieve this the FECG must be acquired via surface electrodes placed on the maternal abdomen, which yields a signal containing the FECG amidst a number of noise sources. Our investigations into the feasibility of "antenatal abdominal FECG analysis" have been on two fronts. The first has been to produce a bedside monitor similar in function to our intrapartum device, whilst the second has been to address the possibility of performing such monitoring in ambulant subjects. At present the antenatal bedside monitor has successfully extracted and processed the FECG in approximately 75% of the cases studied, with subjects ranging from 20 weeks through to term having been monitored. We also have demonstrated the feasibility of the long term monitoring of maternal and fetal heart rate using a portable instrument.

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,

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.

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.

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.

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.

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.

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.

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.

Objectives: The primary objective of this study was to determine the baseline platelet intracellular free Ca2+ concentration in normotensive and hypertensive primigravid women and to note any correlation between variables (ie. platelet intracellular free Ca2+ concentration and arterial blood pressure)., Design: A cross-sectional study of 24 normotensive and 36 primiparous women whose pregnancies were complicated by gestational hypertension, in the third trimester., Methods: Platelet intracellular free Ca2+, serum Ca2+, and renal clearance of Ca2+ were recorded., Results: Mean platelet intracellular free Ca2+ concentration was significantly increased in those subjects whose pregnancies were complicated by proteinuric gestational hypertension (pre-eclampsia) compared with the normotensive primiparous control sample. Those subjects with non-proteinuric pregnancy-induced hypertension did not show this significant increase in baseline platelet intracellular free Ca2+ concentration despite having a persistent and statistically significantly elevated systemic arterial blood pressure. On pooling these data for both normotensive and hypertensive primigravidae a significant positive correlation was noted between the variables of platelet intracellular free Ca2+ concentration and arterial blood pressure. The renal clearance of free Ca2+ was progressively reduced with increasing severity of the disease but had returned to normal 6 weeks postpartum. Serum Ca2+ concentrations corrected for albumin were however higher in the hypertensive patients., Conclusion: Transmembrane Ca2+ fluxes are altered in hypertensive pregnancy by a specific mechanism, probably of placental origin.

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.

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.

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)

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.

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.

Objective: To determine the nature and extent of changes in platelet reactivity in gestational hypertension and pre-eclampsia (using whole blood techniques which may be more physiological than those previously employed)., Design: Cross-sectional observational study., Subjects: 8 normal primigravidae, 16 women with gestational hypertension and 12 women with pre-eclampsia, studied at around 36 weeks gestation., Results: Platelet reactivity (aggregation and release reaction) induced by stimulation with adrenaline was decreased in the pre-eclamptic group. Serum thromboxane B2 production was unchanged in both hypertensive groups compared with the control group., Conclusions: In the context of evidence of platelet activation in pre-eclampsia, our findings are interpreted as reflecting platelet exhaustion.

A total of 92 fetuses have been studied during labour using a technique of real-time fetal electrocardiography. This study showed differences in the PR and QRS intervals between male and female infants and also confirmed previous findings of a positive correlation between QRS width and fetal birthweight. The importance of taking natural biological factors into account in the interpretation of the time constants of the FECG is demonstrated.

Application of pulse oximetry to intrapartum monitoring was investigated in 105 women. No adequate reading could be obtained in 44 cases. Two major sources of artifact, related to probe apposition and signal processing, were identified and excluded. The average arterial oxygen saturation from the fetal scalp was 82% (SD 6%), which is higher than has been inferred from pO2 levels. Readings below 60% or the development of an unstable baseline suggest the presence of substantial hypoxia and acidosis.

Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10(9) cells) when compared with the non-pregnant women (9.0 fmol/10(9) cells P less than 0.001). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10(9) cells) when compared with the 25 normotensive pregnant women (P less than 0.001). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10(9) cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10(9) cells) although the difference was not statistically significant (P less than 0.04). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy.

Non-invasive methods of measuring blood velocity, especially Doppler velocimetry, are being increasingly used in obstetrics to provide observational information. We report a preliminary study of their usefulness in experimental studies. Doppler velocimetry was used to assess blood flow and velocity-time profiles in the common carotid artery of seven women of reproductive age before and during the incremental administration of angiotensin II. Angiotensin II infusion evoked the expected increments in systolic and diastolic arterial pressure and fall in heart rate. Angiotensin II was associated with a dose-dependent fall in maximum blood velocity, which, at an average rise in systolic blood pressure of 23 mmHg, had fallen from 91 +/- 16 to 52 +/- 4 (mean +/- SD, p < 0.01). Absolute maximum blood velocity was strongly correlated with systolic and diastolic blood pressures (p < 0.001 for both). The minimum velocity was unaltered throughout, and the calculated flow did not change significantly (490 +/- 100 cf. 380 +/- 50 ml/min). Overall, these findings are in agreement with those previously reported using invasive methods of monitoring flow during angiotensin II infusion, and further support the usefulness of Doppler velocimetry as an investigative tool in human physiology and pharmacology.However, the pulsatility index, resistance index and systolic/diastolic velocity ratio all fell significantly during angiotensin II infusion (p < 0.01 for all). The conventional interpretation of a fall in these indices, i.e. reduced downstream resistance, is clearly erroneous under these circumstances, since angiotensin II induces arteriolar vasoconstriction. This illustrates the importance of interpretation of Doppler velocity envelopes in the light of pharmacological mechanisms likely to be evoked by the experimental procedure., (Copyright 1991 International Society of Ultrasound in Obstetrics and Gynecology)

A longitudinal study of platelet behaviour (platelet aggregation and release reaction) in whole blood and of serum thromboxane B2 production was performed before, during and after normal pregnancy. The response of platelets to arachidonic acid and to adrenaline was significantly increased in the third trimester. Six weeks after delivery, values were still modestly increased but return to non-pregnant values was complete by 12 weeks. Serum thromboxane B2 production was unchanged throughout pregnancy and the puerperium.

The renal and genital tracts share a common embryological origin; it is thus not surprising that tissues from both can synthesize renin. Preliminary studies showed extremely high concentrations of renin in follicular fluid (FRC) following ovarian stimulation for in-vitro fertilization. This necessitated complete revalidation of the renin assays and showed that data obtained using commercial kits were invalid. An assay protocol was developed using a 1:2 dilution of follicular fluid taken into EDTA (0.3 mol/l) and o-phenanthroline (0.05 mol/l). The assay was performed at pH 7.5 in the presence of excess exogenous (sheep) renin substrate, with incubation periods of 5, 10 and 15 min at 37 degrees C. This protocol resulted in the linear generation of angiotensin I (AI). Activation of inactive renin was performed using eightfold more trypsin than was required for plasma samples. Follicular renin substrate concentrations (FRS) were measured using the same assay methodology as used for measurement of plasma renin substrate concentrations (PRS). Storage of samples at -18 degrees C for up to 2 months was found not to affect the FRC, although repeated freeze-thaw cycles did. FRC and plasma renin concentrations (PRC) were very similar in 25 unstimulated control women, studied in the follicular phase of the menstrual cycle. Trypsin activation increased follicular total renin concentration (FTRC) more than plasma total renin concentration (PTRC) (P less than 0.0001). FRS was slightly higher than PRS (P less than 0.02). Ovarian stimulation with clomiphene citrate (CC; six women) was without effect on these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

The snap-shot capability of the echo-planar imaging technique is used to freeze motion effectively in human fetal studies in utero. These first results obtained at 0.5 T demonstrate diagnostic quality images without the need for averaging. Although averaging improves the image signal to noise ratio, it is shown that significant image blurring is produced even when only eight separate images are averaged over a period of a few seconds. Results are presented showing anatomical detail of the internal organs of the fetus. Some pathology is also demonstrated. These results were obtained using the modulus blipped echo-planar single-pulse technique (MBEST). Running at 10 frames/second, the modulus version of the fast low-angle excitation echo-planar technique (FLEET) is used to produce ungated fetal cardiac movies.

1. The results are presented of a cross-sectional study of 25 non-pregnant and 125 pregnant/postnatal women in whom platelet angiotensin II binding and plasma angiotensin II, plasma renin concentration and plasma renin substrate were measured. 2. Platelet angiotensin II binding was significantly lower in the first-trimester patients as compared with the non-pregnant women (P less than 0.001). Specific binding remained low in the second and third trimesters, and in those patients studied 24 h after delivery. However, higher values, approximating to the non-pregnant level, were found 6 weeks postnatally (n = 25 for each group). 3. Plasma angiotensin II, plasma renin concentration and plasma renin substrate increased in pregnancy, with the increase becoming statistically significant as compared with the non-pregnant women in the second trimester. Maximal median values of plasma angiotensin II and plasma renin substrate were found in the third trimester, but maximal median values of plasma renin concentration were found in the second trimester. The concentrations of all three hormones fell after delivery. 4. There was an inverse correlation between platelet angiotensin II binding and simultaneously measured endogenous levels of plasma angiotensin II (P less than 0.02) and plasma renin substrate (P less than 0.05) in the 25 non-pregnant subjects. These findings support the concept of the angiotensin II receptor concentration being regulated by the plasma angiotensin II level. There was no correlation between platelet angiotensin II binding and plasma renin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

The ultrafast echo-planar magnetic resonance imaging technology, developed and built in Nottingham, has been used to produce the first snapshot images of the human fetus in utero. The imager, operating at a proton resonance frequency of 22 MHz, produces transaxial views in 64 or 128 milliseconds. These images comprise either 64 x 128 or 128 x 128 pixels with an in-plane resolution of 3 x 3 mm2. The slice thickness is 10 mm. Fetal scans of up to 32 contiguous slices are produced in a few minutes. These have been used to study the internal structure of the uterus and the fetus in a range of cases with gestations ranging from 26 weeks to term. Echo-planar imaging seems particularly suitable as an imaging modality since its high speed obviates image blurring arising from fetal motion.

In recent years advances in medical electronic equipment for monitoring, diagnosis and treatment of patients have led to a large increase in the number and variety of instrumentation available to the medical profession. There is a considerable amount of duplication of equipment and in the absence of readily available information buyers are unlikely to make informed decisions about the ideal instrument for their particular circumstances. One method of increasing the users' awareness is a comparative, independent assessment of equipment, with the results disseminated to the interested parties. This paper describes the essential qualities of cardiotocographs: how they are assessed as part of the UK Department of Health's evaluation programme and the measures to inform users of the latest evaluation information.

Plasma renin activity, active renin concentrations, and total renin concentrations were measured serially in 15 women in preterm labor treated with ritodrine. All three parameters showed rapid increases during treatment that depended on ritodrine doses and paralleled changes in maternal pulse rate. The slope of the correlation between plasma renin activity and active renin concentrations suggested an increase in both active renin and renin substrate during ritodrine treatment. In contrast, levels of inactive renin remained unchanged for several hours during ritodrine infusion, showing only a late and much smaller response than that of either total or active renin concentrations. Thus ritodrine treatment results in further activation of an already activated renin-angiotensin system in pregnancy. This activation relates to an increase in both renin enzyme and its substrate. It may be responsible for the disturbance in water balance and the risk of pulmonary edema associated with beta-sympathomimetic drug treatment in preterm labor.