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Biomedical subjects

C W Redman

Publications and source records attributed to C W Redman.

At least 109 records · Page 6Linked to original sources
PubMed1993

Distribution of cell adhesion molecules on CD56++, CD3-, CD16- large granular lymphocytes and endothelial cells in first-trimester human decidua.

Human decidua exhibits a unique infiltrate of large granular lymphocytes (LGL) with a natural killer (NK) cell phenotype (CD56++, CD16-, CD3-). The mechanisms underlying the binding of circulating LGL to vascular endothelium in the decidua and their migration into the decidual stroma were investigated immunohistochemically in first-trimester decidua with antibodies against endothelial adhesion molecules and their counter-receptors on leukocytes. Decidual and peripheral blood LGL were also investigated by flow cytometry. In the immunohistochemical investigations, moderate to large numbers of lymphoid cells in the decidua were found to express the alpha 4 and alpha L integrin subunits, platelet endothelial cell adhesion molecule (PECAM) and intercellular adhesion molecule-1 (ICAM-1). PECAM and ICAM-1 were found on the endothelium of large numbers of decidual blood vessels of all types. Vascular cell adhesion molecule (VCAM), however, was found on the endothelium of only small to moderate numbers of arterioles and venules and a few capillaries, the latter being the main site of migration of leukocytes into the stroma. Weak staining for endothelial leukocyte adhesion molecule (ELAM) was seen only in a moderate number of blood vessels. Flow cytometry revealed expression of the alpha L integrin subunit by 72 +/- 10% and 97 +/- 3% of decidual and peripheral blood CD56+ LGL, respectively, of the alpha 4 integrin subunit by 85 +/- 7% and 90 +/- 5%, of PECAM by 40 +/- 12% and 30 +/- 15%, and of ICAM-1 by 22 +/- 10% and 1 +/- 1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1993

Communicating the significance of the fetal heart rate record to the user.

Fetal heart rate (FHR) records should be presented as measurements derived from numerical analysis. Such analysis requires computerized systems. The Oxford system is the longest established and most tested of the systems available. It could provide the basis for a standardized approach to the numerical analysis of antepartum FHR records. Intrapartum FHR monitoring is of uncertain clinical value. It is premature to recommend standards for numerical analysis to upgrade the present methods of data presentation during labour. Once the patterns of abnormality are better defined numerically such standards will be mandatory because intrapartum FHR records cannot be interpreted reliably by eye.

Diagnosis, Computer-Assisted↗
PubMed1993

Noninvasive assessment of the maternal cerebral circulation by transcranial Doppler ultrasound during angiotensin II infusion.

OBJECTIVE: To examine the relationship between experimentally induced increments in blood pressure and maternal middle cerebral artery flow velocity patterns measured by transcranial Doppler ultrasound (TCD). DESIGN: Prospective experimental study. SETTING: John Radcliffe Maternity Hospital, Oxford. INTERVENTION: Middle cerebral artery flow velocity waveforms were measured using 2 MHz pulsed Doppler ultrasound via the temporal cranial approach at 28 weeks gestation before, during and 10 min following an angiotensin II infusion. SUBJECTS: 101 normotensive primiparous women at 28 weeks gestation. RESULTS: A significant rise in blood pressure and fall in heart rate were demonstrated between pre-infusion and maximum angiotensin II infusion (maximum blood pressure) recordings. Simultaneous changes were observed in all flow velocity indices, shown as a decrease in systolic velocity and pulsatility index, and an increase in diastolic and mean velocity (P < 0.0001). These values all returned to baseline levels 10 min post infusion (P < 0.0001). Statistical analysis suggested that the change in flow velocity is related to the rise in blood pressure rather than the direct effect of angiotensin II on the cerebral circulation. CONCLUSION: Transcranial Doppler can detect changes in the cerebral circulation associated with alterations in blood pressure during pregnancy. The technique needs to be evaluated further in hypertensive disease.

Adult↗
PubMed1993

Second trimester ambulatory blood pressure in nulliparous pregnancy: a useful screening test for pre-eclampsia?

OBJECTIVE: To assess the effectiveness of second trimester 24-hour ambulatory blood pressure measurement as a screening test for pre-eclampsia. DESIGN: Prospective interventional study. SETTING: John Radcliffe Maternity Hospital, Oxford, and Queen Charlotte's and Chelsea Hospital, London. SUBJECTS: One hundred and sixty-two normotensive nulliparous women recruited at hospital booking clinics. INTERVENTION: Ambulatory blood pressure was measured at 18 and 28 weeks gestation using the TM2420 monitor. MAIN OUTCOME MEASURE: The development of pre-eclampsia. RESULTS: Awake systolic and mean arterial pressures were significantly increased (P < 0.02) at 18 weeks in those who later developed pre-eclampsia. Those differences were more apparent at 28 weeks at which time the diastolic pressure was also increased (P < 0.01). At both stages of gestation the higher readings were sustained during sleep so that the awake-sleep differences were similar in relation to each outcome. The group with incipient pre-eclampsia had a significantly faster heart rate at both 18 and 28 weeks (P < 0.002) The sensitivity in predicting pre-eclampsia for a mean arterial pressure of 85 mmHg or greater at 28 weeks was 65%, with a positive predictive value of 31%. The sensitivity and positive predictive value for a test combining a mean arterial pressure of 85 mmHg or greater and a heart rate of 90 bpm or greater were 53% and 45%, respectively. CONCLUSION: Although second trimester ambulatory blood pressure is significantly increased in women who later develop pre-eclampsia, the predictive values for blood pressure alone are low. The efficiency of the test is increased by combining the awake ambulatory heart rate and blood pressure measurement together. If an effective method for preventing pre-eclampsia becomes available (commencing at 28 weeks gestation), then awake ambulatory blood pressure and heart rate may have some clinical value as a screening test.

Adolescent↗
PubMed1993

The effect of placental syncytiotrophoblast microvillous membranes from normal and pre-eclamptic women on the growth of endothelial cells in vitro.

OBJECTIVES: To determine if placental syncytiotrophoblast microvillous (STBM) membranes contain factors which could cause the maternal endothelial cell disturbance thought to be central to the pathophysiology of the maternal syndrome of pre-eclampsia. DESIGN: STMB membranes isolated from pre-eclamptic or normal placentae were added to cultures of endothelial cells and their effect on the proliferation (measured by 3H-thymidine incorporation), viability (measured by 51Cr release) and growth as a monolayer of these cells was determined. Membranes prepared from red blood cells, and non-endothelial adherent and nonadherent cell lines were used as specificity controls. SUBJECTS: STBM membranes were isolated from the placentae of primigravid women, 10 having caesarean sections for breech presentations and 10 for pre-eclampsia. RESULTS: STBM membranes from the placentae of normal and pre-eclamptic women suppressed endothelial cell proliferation to a similar extent and disrupted the cell monolayer to form a honeycomb-like pattern. This change in morphology was seen before significant endothelial cell death occurred. Red blood cell membranes had no effect on either endothelial cell proliferation, viability or monolayer integrity. Endothelial cells from human umbilical arteries and bovine adrenal capillaries were similarly suppressed, but comparable concentrations of STBM membranes had no effect on non-endothelial cell lines. CONCLUSIONS: Syncytiotrophoblast microvillous membranes specifically interfered with endothelial cell growth in vitro. Our results demonstrate that there are trophoblast products which could cause the maternal syndrome of pre-eclampsia through endothelial cell damage.

Cell Division↗
PubMed1993

Fetal cerebral Doppler in the recognition of fetal compromise.

OBJECTIVE: To establish reference ranges for the human fetal middle cerebral artery pulsatility index (MCA PI) for the local obstetric population, and to compare computerised antenatal fetal heart rate (FHR) analysis with the MCA PI as indicators of fetal compromise. DESIGN: Prospective data collection for selected patients. SETTING: High risk pregnancy unit of a teaching hospital. SUBJECTS: Group 1 consisted of 18 healthy women with uncomplicated singleton pregnancies. Group 2 consisted of 27 women admitted to the high risk pregnancy unit over a 9 month period with intrauterine growth retardation and other related problems; all these women were delivered by prelabour caesarean section. INTERVENTION: Serial Duplex sonography to determine fetal MCA PI in Groups 1 and 2. Serial FHR analysis using computerised numerical techniques in Group 2 only. MAIN OUTCOME MEASURES: Serial MCA PI values from 24 to 39 completed weeks of gestation in Group 1. Comparison of serial MCA PI values with FHR analysis in relation to fetal outcome in Group 2. RESULTS: In Group 1 the MCA PI diminished significantly as gestation advanced from 1.73 (SD 0.25) at 24 weeks to 1.38 (SD 0.26) at 39 weeks (P < 0.01). In Group 2 eleven babies were hypoxaemic at delivery: all had low MCA PI values while only nine had an abnormal FHR prior to delivery. CONCLUSION: In normal pregnancy, there is a fall in the fetal MCA PI with advancing gestation which probably reflects a decreasing vascular resistance to fetal cerebral blood flow. Hypoxaemia at delivery appeared to be better recognised by the fetal MCA flow velocity waveform than the FHR analysis. This increased sensitivity, however, was achieved at the expense of a reduced specificity. Larger studies are needed to confirm the findings of this preliminary investigation.

Adult↗
PubMed1993

A randomised prospective study comparing the new vacuum extractor policy with forceps delivery.

OBJECTIVE: To compare assisted vaginal delivery by forceps with delivery by vacuum extractor, where a new vacuum extractor policy was employed which dictated the cup to be used in specific situations. DESIGN: Multicentre randomised controlled trial. SETTING: Four district general hospitals in the West Midlands. SUBJECTS: Six hundred-seven women requiring assisted vaginal delivery, of whom 296 were allocated to vacuum extractor delivery and 311 to forceps. MAIN OUTCOME MEASURES: Delivery success rate, maternal perineal and vaginal injuries, maternal anaesthetic requirements, neonatal scalp and facial injuries. RESULTS: Of the vacuum extractor group, 85% were delivered by the allocated instrument compared to 90% in the forceps group (odds ratio (OR) 0.64; 95% confidence intervals (CI) 0.4-1.04). However, more women in the vacuum extractor group were delivered vaginally (98%) than in the forceps group (96%). There were significantly fewer women with anal sphincter damage or upper vaginal extensions in the vacuum extractor group (11% vs 17%, OR 0.6; 95% CI, 0.38-0.97). There were significantly fewer women in the vacuum extractor group requiring epidural or spinal anaesthetics (25.4% vs 32.7%, OR 0.69; 95% CI 0.49-0.99) or general anaesthetics (1% vs 4%, OR 0.17; 95% CI 0.04-0.76). Although there were significantly more babies in the vacuum extractor group with cephalhaematomata (9% vs 3%, OR 3.3; 95% CI 1.4-7.4) there were fewer babies in the vacuum extractor group with other facial injuries. There were three babies in the forceps group with unexplained neonatal convulsions. CONCLUSIONS: Assisted vaginal delivery using the new vacuum extractor policy is associated with significantly less maternal trauma than with forceps. Further studies are required to assess neonatal morbidity adequately.

Adult↗
PubMed1993

Pre-eclampsia is associated with an increase in trophoblast glycogen content and glycogen synthase activity, similar to that found in hydatidiform moles.

Pre-eclampsia is a placental disorder, but until now, biochemical details of dysfunction have been lacking. During an analysis of the oligosaccharide content of syncytiotrophoblast microvesicles purified from the placental chorionic villi of 10 primigravid women with proteinuric pre-eclampsia, we found an excess of glycogen breakdown products. Further investigation revealed a 10-fold increase in glycogen content (223 +/- 117 micrograms glycogen/mg protein), when compared with controls matched for gestational age at delivery (23 +/- 18 micrograms glycogen/mg protein) (P < 0.01). This was confirmed by examination of electron micrographs of chorionic villous tissue stained for glycogen. The increase in glycogen content was associated with 16 times more glycogen synthase (1,323 +/- 1,013 relative to 83 +/- 96 pmol glucose/mg protein per min) (P < 0.001), and a threefold increase in glycogen phosphorylase activity (2,280 +/- 1,360 relative to 700 +/- 540 pmol glucose/mg protein per min; P < 0.05). Similar changes in glycogen metabolism were found in trophoblast microvesicles derived from hydatidiform moles. Glycogen accumulation in villous syncytiotrophoblast may be a metabolic marker of immaturity of this cell which is unable to divide. The implications of these findings with regard to the pathogenesis of pre-eclampsia are discussed.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗