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Biomedical subjects

C W Redman

Publications and source records attributed to C W Redman.

At least 19 recordsLinked to original sources

Prognosis for pre-eclampsia complicated by 5 g or more of proteinuria in 24 hours.

Forty-two women with pregnancies complicated by pre-eclampsia and heavy proteinuria greater than or equal to 5 g/24 h were referred for conservative management to the high-risk obstetric unit in the John Radcliffe Hospital, Oxford, over a period of 5 years. Hyperuricaemia preceded the onset of heavy proteinuria in all 42 women. Most of the women had severe hypertension, but none developed eclampsia and there were no major maternal complications. Delivery was necessary within 2 weeks of onset of severe proteinuria in 88.1% of cases, although in some very preterm pregnancies delivery could be deferred for 3 or more weeks. Thirty-five women (83%) were delivered by caesarean section, 91% of whom were delivered urgently before the onset of labour. The high rate of urgent preterm operative delivery underlines the uncertainty of advanced pre-eclampsia and the need for close monitoring if delivery is to be deferred. Perinatal mortality was high; all the perinatal deaths occurred in babies of less than 29 weeks gestation. Despite heavy proteinuria, postpartum recovery was good. Three months after delivery, all but one patient had no significant proteinuria. There was no evidence of residual renal dysfunction. Although the outlook for pre-eclampsia with heavy proteinuria is limited, in a few cases pregnancy can be prolonged for significant periods of time without apparently prejudicing maternal safety and permitting enhancement of maturity at birth. The observations justify cautious conservative management even when heavy proteinuria is present.

Antihypertensive Agents

Isolation and characterisation of a subpopulation of human chorionic cytotrophoblast using a monoclonal anti-trophoblast antibody (NDOG2) in flow cytometry.

Human cytotrophoblast cells, isolated from term amniochorion by enzymic digestion and Percoll gradient centrifugation, were characterised by flow cytometry. A panel of 12 anti-trophoblast monoclonal antibodies was screened for labelling of these cells in flow cytometry and the results compared with immunoperoxidase labelling of cytospin preparations and tissue sections. All 12 antibodies were positive for trophoblast on tissue sections, 11/12 were positive on cytospins but only two (NDOG2 and GB25) gave consistent results in flow cytometry. Two-colour labelling with NDOG2 and W6/32, an antibody to HLA-A, -B, -C, demonstrated that 88% of the NDOG2-positive cells also express Class I major histocompatibility complex (MHC) antigens. The NDOG2-positive cytotrophoblast subpopulation was isolated by flow cytometry in sufficient purity (greater than 95%) and yield (3.1 x 10(6)) for use in functional studies in vitro.

Antibodies, Monoclonal

Immunological aspects of pre-eclampsia.

The first pregnancy preponderance and apparent partner specificity of pre-eclampsia suggest that it might have an immune aetiology. The pathogenesis of pre-eclampsia is undefined although it is clear that it is a placental disorder. The maternal syndrome appears to be mediated by placental ischaemia secondary to spiral artery insufficiency. This leads to a hypothesis that pre-eclampsia is a two-stage disease. The first comprises processes that limit the size of the spiral arteries (poor placentation) or obstruct them (acute atherosis). Either or both may have immunological causes although there is no direct evidence. Factors limiting placentation could involve maternal immune intolerance of the fetal allograft, which in their most extreme expression could lead to immunologically mediated abortion. Thus pre-eclampsia may be part of a wider spectrum of pregnancy loss secondary to poor maternal immune accommodation of her genetically disparate fetus. The second stage involves the consequences of the ensuing placental ischaemia. The syndrome is currently tentatively ascribed to diffuse maternal endothelial dysfunction. There is less reason to invoke immunological mechanisms in the second stage although neutrophil activation could explain generalized endothelial damage. It should be clear that these conclusions are provisional and that the greatest need is for more investigation to eliminate the uncertainty which clouds our concepts.

Female

Management of severe pre-eclampsia and eclampsia by UK consultants.

OBJECTIVE: To determine the current management of severe pre-eclampsia and eclampsia in the United Kingdom. DESIGN: One-page postal survey to all (1007) UK consultant obstetricians with questions about use of antihypertensive and anticonvulsant drugs in severe pre-eclampsia and eclampsia, other management strategies, definition of factors determining severity, protocol development and regional review. RESULTS: 688 replies (69.6% response rate). The antihypertensive drugs used were mainly oral labetalol (35%), oral methyl dopa (23%) and parenteral hydralazine (29%); diuretics were not used. Diazepam was the preferred drug in eclampsia. Very few consultants used magnesium sulphate (2%). Anticonvulsants were also prescribed by 85% of consultants to prevent fits; the drugs then preferred were diazepam (41%), phenytoin (30%) and chlormethiazole (24%). Two-thirds of consultants felt there was a need for trials to study the effectiveness of antihypertensive and anticonvulsant drugs. In a woman with proteinuric hypertension, 15% of consultants did not regard the development of headache as indicating severe pre-eclampsia. Consistent management practices were not associated with agreement about protocols. Regional review does not appear to have occurred. CONCLUSION: Antihypertensive and anticonvulsant therapies are widely used but trials are considered necessary. Improvements in the management of women with severe pre-eclampsia or eclampsia might occur if UK obstetricians sought more collective opinion and undertook regional audit of protocols.

Anticonvulsants

Antenatal cardiotocogram quality and interpretation using computers.

OBJECTIVE: To test the application in practice of computerized fetal heart rate (FHR) analysis in pregnancy. DESIGN: Randomized distribution of subjects with computerized analysis automatically revealed or concealed. SETTING: A district general hospital and a teaching hospital outside London. SUBJECTS: 2869 pregnant women studied within a year. OUTCOME MEASURES: Quality and duration of the cardiotocogram; quantitative measurement of FHR variation; number of stillbirths. RESULTS: With interactive advice to the operator, records were of improved quality (up to 28% without signal loss) with potentially much reduced recording time. The short-term FHR variation measured in the last records before intervention is reported for the first time. CONCLUSION: The benefits of using the computers include improvement in record quality and saving of time. In addition, where interpretation depended on estimation of FHR variation there was prima facie evidence of observer misinterpretation; visual analysis was unreliable. A larger trial is now required with more rigorous constraints on intervention.

Cardiotocography

Spontaneous resolution of pre-eclampsia-related thrombocytopenia.

OBJECTIVE: To observe the spontaneous resolution of pre-eclampsia-related thrombocytopenia. DESIGN: A retrospective study. SETTING: High Risk Pregnancy Unit, John Radcliffe Maternity Hospital, Oxford. SUBJECTS: Thirty women with pre-eclampsia complicated by the HELLP/ELLP syndrome who did not receive any specific treatment for their thrombocytopenia. INTERVENTION: Serial platelet counts throughout labour and the puerperium until the platelet counts returned to levels above 100 x 10(9)/l. MAIN OUTCOME MEASURES: Time taken from delivery and platelet nadir for platelet counts to return to levels above 100 x 10(9)/l. The rate of recovery from the platelet nadir was measured by the slope of the serial platelet counts plotted against time. RESULTS: The mean time until platelet count exceeded 100 x 10(9)/l was 67 h (SD 25) after delivery and 44 h (SD 17) from the platelet nadir. All women had counts above 100 x 10(9)/l by 111 h after delivery, and by 88 h after the platelet nadir. Although the time to recovery appeared to depend on the degree of thrombocytopenia, the rate of resolution did not. CONCLUSION: These data can be used as a guide by clinicians as to the expected time course for postpartum resolution of pre-eclampsia-related thrombocytopenia.

Adolescent

Short-term fetal heart rate variation, decelerations, and umbilical flow velocity waveforms before labor.

OBJECTIVE: To determine the value of computerized antepartum measurements of short-term fetal heart rate (FHR) variation and decelerations as a predictor of outcome, and to compare these with measurements of the umbilical artery flow velocity waveform. METHODS: Data were collected from 3563 high-risk patients for measurements of FHR variables (15,702 records) and outcome (intrauterine death or metabolic acidemia on delivery). Detailed analyses were made on 89 patients with one or more records in which short-term FHR variation was 3 milliseconds or less. Umbilical artery flow velocity waveforms were measured concurrently on 2441 occasions in 991 patients. RESULTS: More than half of the patients with FHR variation of 3 milliseconds or less were identified before 31 weeks. When short-term FHR variation exceeded 3 milliseconds, there were no intrauterine deaths and only one instance of metabolic acidemia on cesarean delivery. When FHR variation fell below 2.6 milliseconds, 34% of the subjects had metabolic acidemia on cesarean or intrauterine death. The appearance or absence of decelerations was an unreliable guide to outcome. The correlation between FHR variation and the umbilical artery flow velocity waveform was low (r = 0.32). The population studied contained some patients without placental vascular disease or, in five with pre-eclampsia, without abnormal umbilical artery velocity waveforms but with grossly reduced FHR variation. CONCLUSION: Reduction in short-term FHR variation, as measured by computer, reliably predicts fetal outcome and is a more general measure of fetal well-being than are umbilical artery flow velocities.

Blood Flow Velocity

Approximate entropy, a statistic of regularity, applied to fetal heart rate data before and during labor.

OBJECTIVE: To determine whether approximate entropy (ApEn), a new statistic of regularity, when applied to fetal heart rate (FHR) data antepartum or in labor, would offer an advantage over standard statistics of variation in predicting outcome. METHODS: A large data base of antepartum FHR records collected in clinical practice over 10 years was available. Two data sets in labor were stored on disk in small computers interfaced to fetal monitors on-line. Outcomes were assessed using blood gas values on delivery and Apgar scores. RESULTS: Antepartum, when the most favorable form of ApEn was used on 769 good-quality FHR records, the correlation with measurement of short-term variation was high. This was especially true when the fetal pulse interval variation fell below the normal range (less than 6 milliseconds short-term; r = 0.93) and in 20 other records with sinusoidal variation (r = 0.96). Approximate entropy varied with fetal sleep cycles and took longer to calculate than FHR variation. During the last hour of labor, in 319 records, there was no significant correlation between umbilical artery base deficit values on delivery and ApEn measurement. In 871 additional good-quality records of fetuses with normal outcome, the mean (+/- standard error [SE]) ApEn (0.95 +/- 0.005) was significantly greater than in 22 records (0.88 +/- 0.028) from fetuses with abnormal outcome (umbilical artery base deficit more than 12 mmol/L and Apgar score of 3 or less at 1 minute). However, consideration of the frequency distributions of these measurements showed that ApEn did not discriminate between normal and abnormal outcomes. The SD of fetal pulse intervals rose in labor whereas ApEn values fell, confirming that this new statistic of regularity differs from standard statistics of variation. CONCLUSION: Approximate entropy offered no advantage over measurement of short-term FHR variation antepartum, and neither measurement predicted outcome in labor.

Adult

Congenital heart block with hydrops fetalis treated with high-dose dexamethasone; a case report.

A 32-year-old woman with systemic lupus erythematosus was found to have a fetus with heart block and fetal ascites at 23 weeks gestation. Treatment with high-dose corticosteroids ameliorated the early signs of heart failure, although the fetal heart rate gradually fell from 48 beats/min to 42 beats/min by 34 weeks. Sudden deterioration of the fetal state occurred at 35 weeks, and this only partially responded to digitalisation. Neonatal death occurred on Day 18 from the consequences of severe birth asphyxia. The relationship and pathogenesis of anti-Ro antibodies, congenital heart block and hydrops fetals are discussed, together with the in utero management of this condition.

Adult

Detection of fetal cells in maternal blood.

We report the detection of fetal cells in the maternal circulation by enzymatic amplification of a single copy gene sequence that was fetal-specific. Fetal HLA-A2-positive cells were sorted from maternal HLA-A2-negative cells by flow cytometry and confirmed by demonstration of a fetal-specific HLA-DR4 sequence. However, this sequence could not be detected in unenriched maternal DNA prepared at 28 and 32 weeks' gestation. The sensitivity of detection was 1 HLA-DR4-positive cell in 10(5) HLA-DR4-negative cells. We conclude that prenatal diagnosis of paternally inherited autosomal-dominant genetic defects may be possible by selective gene amplification of maternal peripheral blood. However, preliminary enrichment for fetal cells may be necessary.

Female

Short-term variation in abnormal antenatal fetal heart rate records.

In a retrospective study the relation of reduced fetal heart rate variation to fetal acidemia was analyzed with a computerized system for numeric analysis. Between 1983 and 1987, 78 pregnancies were identified in which at least one record of the fetal heart rate had very low long-term variation. The outcome was analyzed to determine the numeric criteria of fetal heart rate variation that most efficiently detect a fetus that will die (preterminal) or is dying (terminal). Because fetal compromise was found on occasion to be associated with a slow sinusoidal fetal heart rate rhythm that increased measures of long-term variation. It was necessary to define a new index of short-term fetal heart rate variation (the 1/16 minute epoch-epoch variation). This was closely related to long-term variation (r = 0.9) but provided better detection of preterminal records as judged by metabolic acidemia at delivery or intrauterine death.

Adult