Search PubMed⌕ Search

Biomedical subjects

C W Redman

Publications and source records attributed to C W Redman.

At least 55 records · Page 3Linked to original sources
PubMed1998

Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis.

OBJECTIVE: Our aim was to seek evidence for circulating leukocyte activation in preeclampsia. STUDY DESIGN: Whole blood flow cytometric techniques were used to analyze surface markers of activation (CD11b, CD14, CD23, CD49d, CD62L, CD64, CD66b, HLA-DR) and intracellular reactive oxygen species. Samples were taken from 21 women with preeclampsia, 21 matched normal pregnant women, 21 healthy nonpregnant controls, and 6 nonpregnant patients with septicemia. Ten preeclamptic cases were followed up 6 weeks post partum. RESULTS: The leukocytes of healthy pregnant women differed substantially and significantly from those of nonpregnant women (increased CD11b, CD14, and CD64 and increased intracellular reactive oxygen species). In preeclampsia there was, in addition to these changes, reduced expression of L-selectin and further increases in intracellular reactive oxygen species. The changes found in normal pregnancy and preeclampsia were similar, but not identical, to those found in sepsis. CONCLUSIONS: Normal third-trimester pregnancy is characterized by remarkable activation of peripheral blood leukocytes, which is further increased in preeclampsia.

Adult↗
PubMed1998

Circulating markers of oxidative stress are raised in normal pregnancy and pre-eclampsia.

OBJECTIVE: To determine whether circulating markers of oxidative stress are elevated in pre-eclampsia when appropriate precautions are taken to prevent in vitro oxidation DESIGN: A prospective study. SETTING: Nuffield Department of Obstetrics and Gynaecology, Oxford and The William Harvey Institute, London. SAMPLE: Three groups of women: those with pre-eclampsia (n = 19), control pregnant women (n = 19) matched for gestation, age and parity and a group of non pregnant individuals of reproductive age (n = 7). METHODS: Citrated plasma was stored at -80 degrees C with 20 micromol beta hydroxytoluene to prevent auto-oxidation. Plasma samples were assayed for levels of 8 epi-prostaglandin F2alpha, lipid hydroperoxides, malondialdehyde and also the lipid soluble antioxidant vitamin E. RESULTS: There were no differences in 8 epi-prostaglandin F2alpha, lipid peroxide or malondialdehyde levels between the groups of women with pre-eclampsia and those acting as pregnant controls. However, lipid hydroperoxides and malondialdehyde were significantly raised in both pre-eclampsia and normal pregnancy, compared with nonpregnant women. Vitamin E levels were similar in women with pre-eclampsia and those with a normal pregnancy, but in both groups levels were significantly higher than in nonpregnant women. CONCLUSION: Circulating markers of oxidative stress are raised in normal pregnancy and pre-eclampsia.

Adult↗
PubMed1998

Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies.

OBJECTIVE: To investigate whether syncytiotrophoblast microvilli (STBM) are shed into the maternal circulation in increased amounts in pre-eclamptic pregnancies as a possible cause of maternal vascular endothelial dysfunction. DESIGN: A time-resolved fluoroimmunoassay was developed to measure STBM levels in peripheral and uterine venous plasma from normal pregnant and pre-eclamptic women. Three colour flow cytometry was used to assess the microparticulate nature of the STBM in pregnancy plasma. The effects of these plasmas on endothelial cell proliferation was compared and a correlation with the levels of STBM detected was sought. SETTING: A laboratory investigation using clinical samples obtained from an obstetric practice in a teaching hospital. SAMPLES: Peripheral venous plasma from 20 women with established pre-eclampsia, 20 normal pregnant women matched for age, gestation and parity, and 10 nonpregnant women of reproductive age. Paired uterine and peripheral venous plasma taken at caesarean section from 10 women with pre-eclampsia and 10 unmatched normal pregnant women. RESULTS: STBM were detected in the plasma of pregnant women by both flow cytometry and time-resolved fluoroimmunoassay. Significantly higher levels of STBM were found in women with established pre-eclampsia (P=0.01). STBM concentrations were higher in uterine venous plasma than in concurrently sampled peripheral venous plasma, confirming their placental origin. A significant correlation was found between the amount of STBM in the plasma and endothelial cell inhibitory activity. CONCLUSIONS: STBM are shed into the maternal circulation (microvillous deportation) and are present in significantly increased amounts in pre-eclamptic women. They may contribute to the endothelial dysfunction underlying the maternal syndrome of pre-eclampsia.

Adult↗
PubMed1998

Do routine antibiotics after loop diathermy excision reduce morbidity?

OBJECTIVE: To evaluate whether routinely giving an antibiotic after loop diathermy excision of the cervical transformation zone reduced post-operative vaginal loss. DESIGN: Prospective, randomised, double-blind placebo controlled parallel study. PARTICIPANTS: Five hundred women undergoing loop diathermy excision in a colposcopy clinic. INTERVENTION: Administration of either ofloxacin 400 mg (2x200 mg) once daily for 5 days or an identical placebo. MAIN OUTCOME MEASURE: Vaginal loss, assessed using a pictorial chart. RESULTS: No significant difference in post-operative vaginal loss was found. CONCLUSION: Routine antibiotic prophylaxis after loop diathermy excision is not justified.

Adult↗
PubMed1998

Association of glutathione S-transferase GSTM1 and GSTT1 null genotypes with clinical outcome in epithelial ovarian cancer.

Epithelial ovarian cancer is generally associated with a poor outcome, although the mechanisms that determine survival and progression-free interval (PFI) are unclear. Data from ovarian tumors showing associations between (a) null genotypes at the glutathione S-transferase GSTM1 and GSTT1 loci and expression of p53 protein and (b) outcome and expression of p53 suggest that polymorphism at these loci is a factor determining outcome. Accordingly, we have studied the association between the GSTM1 null and GSTT1 null genotypes and survival and PFI in 148 women with epithelial ovarian cancer. Although we did not find an association between individual genotypes and outcome, women with both GSTM1 null and GSTT1 null genotypes demonstrated poorer survival (P = 0.001) and reduced PFI (P = 0.003). Thus, no cases with both these genotypes survived past 42 months postdiagnosis. In contrast, 43% of the women without this combination survived beyond this time. Because response to chemotherapy is a major factor determining outcome in ovarian cancer, we also examined the data for associations between the glutathione S-transferase genotypes and response to such treatment. Thus, in 78 patients treated with chemotherapy, the combination of GSTM1 null and GSTT1 null was associated with unresponsiveness to primary chemotherapy (P = 0.004); none of the eight patients with both these genotypes responded, compared with 38 of 70 (54%) of patients with other genotype combinations. The effect of the combination of genotypes on survival and PFI was lost in a multivariate model that included response to chemotherapy as a confounding factor. This suggests that the combination of GSTM1 null/GSTT1 null is associated with outcome because of its influence on response to chemotherapy. These preliminary findings may provide a basis for the selection of patients for treatment with chemotherapeutic agents.

Adolescent↗
PubMed1997

Presence of fetal DNA in maternal plasma and serum.

BACKGROUND: The potential use of plasma and serum for molecular diagnosis has generated interest. Tumour DNA has been found in 'the plasma and serum of cancer patients, and molecular analysis has been done on this material. We investigated the equivalent condition in pregnancy-that is, whether fetal DNA is present in maternal plasma and serum. METHODS: We used a rapid-boiling method to extract DNA from plasma and serum. DNA from plasma, serum, and nucleated blood cells from 43 pregnant women underwent a sensitive Y-PCR assay to detect circulating male fetal DNA from women bearing male fetuses. FINDINGS: Fetus-derived Y sequences were detected in 24 (80%) of the 30 maternal plasma samples, and in 21 (70%) of the 30 maternal serum samples, from women bearing male fetuses. These results were obtained with only 10 microL of the samples. When DNA from nucleated blood cells extracted from a similar volume of blood was used, only five (17%) of the 30 samples gave a positive Y signal. None of the 13 women bearing female fetuses, and none of the ten non-pregnant control women, had positive results for plasma, serum or nucleated blood cells. INTERPRETATION: Our finding of circulating fetal DNA in maternal plasma may have implications for non-invasive prenatal diagnosis, and for improving our understanding of the fetomaternal relationship.

Case-Control Studies↗
PubMed1997

Activin A and inhibin A as possible endocrine markers for pre-eclampsia.

BACKGROUND: Inhibin A and activin A are produced by the placenta during human pregnancy. This study aimed to measure circulating concentrations of inhibin A, pro alpha C-containing inhibins, and activin A in the serum of women with pre-eclampsia and of healthy matched control pregnant women, and to establish the molecular-weight forms of circulating inhibin A and activin A in pre-eclampsia. METHODS: In a retrospective cross-sectional study, blood samples were taken from 20 women in hospital with established pre-eclampsia, and from 20 control pregnant women attending antenatal clinics, who were matched for duration of gestation (pre-eclampsia mean 29.15 [SD 3.75] weeks; controls 29.30 [3.93] weeks), parity, and maternal age. Serum samples were analysed for inhibin A, inhibin B, pro alpha C, and activin A. Pooled samples of control (n = 3) and pre-eclampsia serum (n = 3) subsequently underwent fast protein liquid chromatographic analysis to assess the molecular-weight forms of inhibin A and activin A. Results are expressed as mean and SD for all variables measured. FINDINGS: Serum concentrations of inhibin A, activin A, and pro alpha C were significantly higher in pre-eclampsia than in control normal pregnancy (inhibin A 3.05 [1.8] vs 0.36 [0.14] ng/mL, p < 0.001; activin A 38.08 [25.88] vs 3.95 [2.32] ng/mL, p < 0.001; pro alpha C-containing inhibins 2.2 [0.81] vs 0.71 [0.33] ng/mL, p < 0.001). Inhibin B concentrations in maternal serum were not increased. Molecular-weight forms of inhibin A (32 kDa) and activin A (> 100 kDa) were similar in pre-eclampsia and normal pregnancy. The mean concentrations of hCG were 59.05 [43.98] and 16.3 [8.72] ng/mL, respectively. INTERPRETATION: Higher maternal serum concentrations of inhibin A, pro alpha C, and total activin A in pre-eclampsia than in control pregnancies could be helpful in the diagnosis of pre-eclampsia. These changes are interpreted as further evidence for trophoblast dysfunction in pre-eclampsia.

Activins↗
PubMed1997

Increased maternal plasma levels of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin) in preeclampsia.

The physiological significance of soluble adhesion molecules has not been elucidated but it has been reported that a number of cytokines may increase the cleavage of soluble adhesion molecules. The fact that preeclampsia is associated with both increased cytokine concentrations and endothelial cell damage led us to analyse levels of soluble adhesion molecules in preeclamptic women and to compare these levels to the disease state. Since the cytokine network is altered by reproduction, the present study also raised the question as to whether levels of soluble adhesion molecules differ between pregnant and non-pregnant women, and whether variations occur with relation to gestational age or delivery. Levels of soluble adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin) in 25 preeclamptic women were compared to those in healthy pregnant women matched for age, parity and gestation, and the levels of soluble adhesion molecules of 40 healthy pregnant women at different gestational ages were determined and compared to those of 15 non-pregnant women. Concentrations were measured by ELISAs. Levels of ICAM-1, VCAM-1 and E-selectin concentrations were elevated in preeclamptic pregnancies, whereas serum levels in normal pregnancy did not differ from those of non-pregnant women. No changes were observed in relation to gestational age or delivery.

Adult↗
PubMed1997

A randomised controlled comparison of betamethasone with dexamethasone: effects on the antenatal fetal heart rate.

OBJECTIVE: To compare the effects of maternal administration of betamethasone and dexamethasone on fetal heart rate, using computerised numerical analyses, and to examine the association between changes in short term variation and the timing and indication for delivery. SETTING: John Radcliffe Hospital, Oxford. SAMPLE: Fifty-nine women with singleton pregnancies, who were at risk of delivery before 34 weeks of gestation, had received no steroids in the preceding week and could give informed consent. METHODS: Women were randomised on a double-blind basis to receive either betamethasone or dexamethasone. The fetal heart rate was recorded (60-minute duration at similar times of day) before steroid administration and on each of the following two days; changes were measured by computerised analyses. MAIN OUTCOME MEASURES: Changes in short term variation and long term variation of fetal heart rate or the number of fetal movements. Statistical analysis was nonparametric. RESULTS: Betamethasone and dexamethasone had no differential effects on the computerised cardiotocography. However, both steroids decreased baseline fetal heart rate, increased long term variation, increased short term variation, and decreased fetal movements on the first day after steroid administration, and decreased high fetal heart rate variation and decelerations on the second day. Among 13 women who were delivered within one week of steroid administration, smaller rises in short term variation on day one were associated with delivery for fetal indications. CONCLUSIONS: Both betamethasone and dexamethasone produced transient, unexplained changes in the fetal heart rate over the two days following steroid administration. Larger changes in short term variation were associated with fetal wellbeing. It is important to recognise that such changes are a physiological response of the human fetus to steroid administration.

Adult↗
PubMed1997

Human placental syncytiotrophoblast microvillous membranes impair maternal vascular endothelial function.

OBJECTIVE: To investigate the hypothesis that, should there be an increase in deported syncytiotrophoblast microvillous membrane fragments in pre-eclampsia, it may cause maternal vascular endothelial dysfunction. DESIGN: Syncytiotrophoblast microvillous membrane (STBM) vesicles, prepared from normal term placentae, were perfused through small subcutaneous arteries isolated from fat biopsies obtained at caesarean section. Endothelial function of these arteries was studied by determining acetylcholine-induced relaxation after preconstriction with noradrenaline. As controls, physiological buffer or red blood cell membranes in physiological buffer were used and endothelial function similarly estimated. Transmission electron microscopy was performed on arteries after perfusion. SAMPLE: STBM vesicles, isolated from the placentae of three healthy women undergoing elective caesarean section for reasons unrelated to pre-eclampsia, were suspended in physiological buffer. Subcutaneous fat arteries were obtained from a separate group of 13 normotensive pregnant women, also undergoing elective caesarean section at term. RESULTS: Perfusion with red blood cell membranes or physiological buffer had no significant effect on the concentration dependent relaxation in arteries preconstricted with noradrenaline. However, after 2 h perfusion with STBM vesicles, arteries showed a significant reduction in relaxation to acetylcholine, indicative of altered endothelial function. Transmission electron microscopy of arteries perfused with STBM vesicles confirmed endothelial disruption. CONCLUSIONS: STBM vesicle perfusion specifically altered the relaxation response of preconstricted maternal subcutaneous fat arteries to acetylcholine, suggesting an alteration in endothelial dependent relaxation. Deported microvilli may therefore be capable of producing endothelial cell damage and endothelial dysfunction observed in the maternal syndrome of pre-eclampsia.

Arteries↗
PubMed1997

The effect of nifedipine and methyldopa on maternal cerebral circulation.

OBJECTIVE: To study how the treatment of severe gestational hypertension affects maternal middle cerebral artery velocimetry. DESIGN: Prospective, clinical, descriptive study. SETTING: John Radcliffe Maternity Hospital, Oxford, England. PARTICIPANTS: Pregnant and puerperal women who required acute or chronic antihypertensive treatment with nifedipine (n = 46) or methyldopa (n = 26), respectively. METHODS: Transcranial Doppler ultrasound examinations of maternal middle cerebral arteries were performed before and 45 min after nifedipine; and before and 48 hours after the onset of methyldopa therapy. Blood pressure and heart rate were also recorded. MAIN OUTCOME MEASURES: Clinical and transcranial Doppler changes induced by the antihypertensive medication. RESULTS: Blood pressure and middle cerebral artery velocities decreased significantly following both short- and long-acting antihypertensive therapy. Nifedipine-induced changes were more pronounced and uniform than those found after methyldopa (16.7% and 6.4% decrease in middle cerebral artery mean velocity, respectively). The middle cerebral artery mean velocity decrease was independent of changes in the blood pressure or heart rate. CONCLUSIONS: Maternal cerebral haemodynamics are influenced by antihypertensive treatment. The reduction of middle cerebral artery flow velocities following administration of nifedipine and methyldopa may suggest that cerebral vasodilatation is occurring, which is consistent with the concept that cerebral vasospasm is present in women with pre-eclampsia. The cerebral vasodilatation could result from a direct effect of the medication on the arteries in question.

Antihypertensive Agents↗
PubMed1997

Elevated levels of serum nitrate, a stable end product of nitric oxide, in women with pre-eclampsia.

OBJECTIVES: Nitric oxide released from vascular endothelial cells is a potent vasodilator and inhibits platelet adhesion. It has been suggested that decreased nitric oxide production from dysfunctional endothelial cells is implicated in the pathophysiology of pre-eclampsia. In this study evidence was sought for abnormal production of nitric oxide in pre-eclamptic women. PARTICIPANTS: Blood was collected from 20 women presenting with pre-eclampsia, from 20 matched healthy pregnant controls and from 12 nonpregnant women of childbearing age. METHODS: Serum nitrate, the stable end metabolite of nitric oxide, was measured by vanadium III chloride reduction and chemiluminescence. RESULTS: Sera from women with pre-eclampsia had significantly higher nitrate concentrations (mean 47.4 mumol/L [SD 13.6]) compared with healthy pregnant (mean 31.2 mumol/L [SD 9.14]) and nonpregnant (mean 32.1 mumol/L [SD 10.0]) controls. CONCLUSIONS: These results do not support the hypothesis that decreased endothelial cell nitric oxide production may be important in the pathophysiology of pre-eclampsia. On the contrary, serum nitrate levels are increased which may reflect either increased production of nitric oxide from an unidentified source or decreased elimination through the kidneys.

Adult↗