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Biomedical subjects

C W Redman

Publications and source records attributed to C W Redman.

At least 91 records · Page 5Linked to original sources
PubMed1994

Progression of cervical intraepithelial neoplasia to cervical cancer: interactions of cytochrome P450 CYP2D6 EM and glutathione s-transferase GSTM1 null genotypes and cigarette smoking.

The factors that determine progression of cervical intraepithelial neoplasia (CIN) to squamous cell carcinoma (SCC) are unknown. Cigarette smoking is an independent risk factor for cervical neoplasia, suggesting that polymorphism at detoxicating enzyme loci such as cytochrome P450 CYP2D6 and glutathione S-transferase GSTM1 may determine susceptibility to these cancers. We have studied the frequencies of genotypes at these loci in women suffering low-grade CIN, high-grade CIN and SCC. A non-cancer control group was provided by women with normal cervical histology suffering menorrhagia. Comparison of the frequency distributions of the CYP2D6 PM, HET and EM genotypes (G-->A transition at intron 3/exon 4 and base pair deletion in exon 5) revealed no significant differences between the menorrhagia and SCC groups. Frequency distributions in the menorrhagia group, however, were significantly different (P < 0.04) from those in the low- and high-grade CIN groups. Thus, the proportion of EM was significantly larger (P < 0.03) and of HET generally lower. We found that the frequency of GSTM1 null in the menorrhagia and case groups was not significantly different. Interactive effects of enzyme genotypes with cigarette smoking were studied by comparing the multinomial frequency distributions of CYP2D6 EM/GSTM1 null/smoking over mutually exclusive categories. These showed no significant differences between the menorrhagia group and SCC or low-grade CIN groups. The frequency distribution in high-grade CIN, however, was significantly different to that in the menorrhagia group and in both SCC and low-grade CIN groups. This study was identified, for the first time, an inherited characteristic in women with high-grade CIN who appear to be at reduced risk of SCC. Thus, women with CYP2D6 EM who smoke have increased susceptibility to high-grade CIN but are less likely to progress to SCC, possibly because they effectively detoxify an unidentified chemical involved in mediating disease progression.

Adult↗
PubMed1994

Suppression of allogeneic reactivity in vitro by the syncytiotrophoblast membrane glycocalyx of the human term placenta is carbohydrate dependent.

Immunosuppressive factors isolated from trophoblast are known to block both innate and major histocompatibility complex (MHC)-dependent cell-mediated immune responses in vitro and, in some cases, in vivo. We investigated the biochemical nature of these factors, which is presently unknown. Immunosuppressive activity, assessed by inhibition of two-way MLR, was extracted from term syncytiotrophoblast microvilli using 3 M KCl. The activity resisted both extensive pronase digestion and heating to 90 degrees C for 1 h, demonstrating that intact membrane proteins were not required. Although purified protein-linked oligosaccharides released by hydrazinolysis from the syncytiotrophoblast membrane were themselves inactive, they blocked the immunosuppressive activity of the KCl extract. After pronase digestion, the activity could be fractionated by TSK 55S gel filtration, followed by C18 reverse-phase chromatography. Sequential exoglycosidase digestion of hydrazine-released sugars of the active fraction demonstrated that it contained neutral N-linked oligomannose and hybrid oligosaccharides, which normally make up < 3% of the total syncytiotrophoblast-derived protein glycan library. These glycopeptides of the active fraction were associated with membrane phospholipid micelles. The possible mechanism by which incompletely processed N-linked oligosaccharides expressed by a variety of syncytiotrophoblast membrane glycoproteins may block allogeneic reactivity when presented as polyvalent sugar groups is discussed.

Carbohydrate Metabolism↗
PubMed1994

Intervention debulking surgery in advanced epithelial ovarian cancer.

OBJECTIVE: To study whether intervention debulking surgery improves survival in patients with advanced ovarian cancer who have bulky (> 2 cm) residual disease after primary surgery. DESIGN: A prospective multicentre randomised study. SETTING: Hospitals in the West Midlands. SUBJECTS: Ovarian cancer patients with bulky residual disease after primary surgery who are considered well enough to receive cis-platinum based chemotherapy and further surgery. METHODS: Eligible patients were randomised to receive combination chemotherapy alone or combined with intervention debulking surgery. MAIN OUTCOME MEASURE: Survival was assessed using product limit method and log-rank test. RESULTS: Seventy-nine patients were entered into the study. Thirty-seven patients were randomised to intervention debulking surgery, 25 (67%) of whom underwent intervention debulking surgery, which was performed a median of 13 weeks after primary surgery. The median survival for the intervention debulking surgery group was 15 months (95% CI 10-20 mo) and that of those randomised to chemotherapy alone, which was 12 months (95% CI 8-16 mo), were not significantly different (hazard ratio = 0.71; 95% CI 0.44-1.13). CONCLUSION: Intervention debulking surgery may not improve survival in patients with advanced ovarian cancer.

Adult↗
PubMed1994

Dexamethasone and fetal heart rate variation.

OBJECTIVE: To determine the effect of maternal administration of dexamethasone on fetal heart rate and its variation. DESIGN: Retrospective analysis of computerised data derived from cases studied over three years. SETTING: High risk pregnancy unit, John Radcliffe Hospital, Oxford. SUBJECTS: Twenty-eight pregnant women, at 27 to 32 weeks of gestation, to whom dexamethasone was given to accelerate pulmonary maturation in the expectation of preterm delivery. METHODS: Dexamethasone (two doses of 12 mg intramuscularly, 12 h apart) was given on 51 occasions at weekly intervals (one to four occasions per patient). Complete data were available for cardiotocograph analysis from computerised measurement of fetal heart rate variables for two days before and four days after dexamethasone and, in 19 women, measurements of umbilical arterial flow velocity waveforms before and after dexamethasone. RESULTS: In 10 pregnancies without fetal distress there was a highly significant (P < 0.01) transient rise in short term fetal heart rate variation after dexamethasone administration, from means (SE) 6.4 (0.28) to 9.8 (0.4) ms. In 18 pregnancies with subsequent delivery for fetal distress (abnormal fetal heart rate pattern) and high umbilical arterial resistance index [mean 0.93 (0.06 SE)], the rise in short term fetal heart rate variation was less (P < 0.01), from mean (SE) 5.4 (0.26) to 6.1 (0.48) ms. In a further case of discordant twin pregnancy, the larger twin continued to respond to dexamethasone administrations with a rise in fetal heart rate variation for five weeks; the smaller twin, with maintained tachycardia and reduced umbilical arterial end-diastolic flow velocity, failed to respond after the first two weeks. CONCLUSION: The results show that maternal dexamethasone administration normally causes a rise in fetal heart rate variation for up to a day. This rise is reduced in pre-eclampsia or intrauterine growth retardation, associated with a reduction in umbilical flow, perhaps because of a consequential lower concentration of steroid in the fetus. The results contrast with those for betamethasone which has been reported to reduce fetal heart rate variation.

Blood Flow Velocity↗
PubMed1994

Neonatal outcome after pregnancy complicated by abnormal velocity waveforms in the umbilical artery.

The neonatal outcome of 61 infants born after pregnancies complicated by absent or reversed end diastolic flow velocities (AREDFV) in the fetal umbilical artery was compared with that of 61 controls matched for gestational age born after high risk pregnancies with documented forward end diastolic flow velocities (EDFV). The AREDFV group was significantly more growth retarded, had lower platelet counts at birth, and were more likely to become significantly thrombocytopenic in the first week after birth. Owing to concerns about the possible increased risk of necrotising enterocolitis in newborn infants after AREDFV, this group was started on enteral feeds later and was more likely to receive parenteral nutrition than the EDFV group. Seven infants with AREDFV and one control infant developed necrotising enterocolitis.

Adolescent↗
PubMed1994

Distribution of cell adhesion molecules in decidua of early human pregnancy. An immunohistochemical study.

BACKGROUND: The aim of the study was to investigate human decidua for cell adhesion molecules involved in interactions between the various different maternal and fetal cell populations, homing of the unusual intradecidual population of CD56+ lymphocytes, and organization of the decidual extracellular matrix. EXPERIMENTAL DESIGN: First trimester human decidua from normal pregnancies was investigated immunohistochemically with antibodies against integrin subunits (alpha 1-6, alpha L, alpha M, alpha X, alpha IIb, alpha V, beta 1, beta 3, and beta 4), platelet-endothelial cell adhesion molecule, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and L-selectin. RESULTS: Endometrial glands stained for alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha V, beta 1, beta 3, and beta 4, and stromal cells for alpha 1, alpha 3, alpha 5, alpha 6, alpha V, beta 1, beta 3, ICAM-1, and VCAM-1. Endothelium stained for alpha 1, alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, alpha V, alpha IIb, beta 1, beta 3, and beta 4; platelet-endothelial cell adhesion molecule and ICAM-1 also were found on the endothelium of a large number of blood vessels of all types, and VCAM-1 on the endothelium of a moderate number of arterioles and venules, and a few capillaries. Weak staining for E-selectin was seen in a moderate number of arterioles and venules. Large numbers of lymphocytes stained for alpha 4, alpha L, alpha M, alpha X, beta 1, and moderate or small numbers for alpha 1, alpha 3, alpha 5, alpha v, beta 3, platelet-endothelial cell adhesion molecule, ICAM-1, and L-selectin. CONCLUSIONS: Decidual stromal cells, like endometrial glands and endothelium, express integrins that bind basement membrane components. These integrins represent the basis for the formation of the pericellular basement membrane of these cells. They also bind certain glycoproteins that support outgrowth and attachment of the trophoblast in vitro. Vitronectin-binding integrins on endometrial glands, stromal cells, and endothelium may be involved in adhesion of the trophoblast through vitronectin on its surface. From our findings and published data it seems that adhesion of alpha 1 beta 2 (leukocyte function-associated antigen-1) on lymphocytes to ICAM-1 on the endothelium plays the most important role in the migration of CD56+ lymphocytes from the peripheral blood into the decidua. The expression of several beta 1 (VLA) integrins on lymphocytes suggests that these cells are activated, and, like the expression of ICAM-1 and VCAM-1 on stromal cells, probably contributes to their retention in the decidual stroma.

Cell Adhesion Molecules↗
PubMed1993

Management of severe, early pre-eclampsia: is conservative management justified?

A retrospective analysis was performed to assess the fetal and maternal benefits of allowing women presenting with severe pre-eclampsia between 24 and 32 weeks to continue their pregnancy following treatment of their hypertension. Cases presenting in Oxford (conservative management) and in Birmingham (stabilisation and early intervention) were compared. Patients were considered to require treatment when their systolic blood pressure was > or = 170 mmHg systolic or > or = 110 mmHg diastolic, associated with at least 1+ proteinuria and hyperuricaemia. We compared gestation at delivery, birth weight and neonatal complications for each group, and any maternal morbidity. There were 28 patients in each group. Gestational age at delivery was significantly less in the group managed by early intervention. Those women managed conservatively gained a mean of 9.5 days (range 2-26 days; P < 0.05), and their birthweight was significantly greater (P < 0.05). There was a significant difference between the length of stay in the neonatal intensive care unit between the 2 groups (P < 0.05), the babies of those women managed conservatively staying a mean of 7.4 days less. There were fewer neonatal complications in those cases managed conservatively, the number of newborns with 1 or more complications in the early intervention group being 18 (64.3%), compared with 8 (28.6%) in the expectant management group (P = 0.0001). All of the women in the group managed by early intervention recovered with no severe complications. However, those women managed conservatively had a higher incidence of HELLP (2 cases) and ELLP syndrome (2 cases), 1 case requiring temporary renal dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1993

Large fetal heart rate decelerations at term associated with changes in fetal heart rate variation.

OBJECTIVE: The objective was to determine whether large antepartum decelerations in fetal heart rate were associated with a switch from high to low fetal heart rate variation, suggestive of a change in sleep state, and whether the variation predicted outcome. STUDY DESIGN: Retrospective computerized analysis of 10,272 cardiotocographic records from 3998 patients at 37 to 42 weeks' gestation from four centers in England and Italy identified 140 good-quality records with large decelerations (more than 20 lost beats in area). RESULTS: In otherwise normal cardiotocograms a large deceleration had a 40% chance of association with a downward change in fetal heart rate variation (69% when the deceleration exceeded 100 lost beats). The change resembled that occurring naturally with behavioral states. Uterine contractions did not always precede large decelerations. When they did, the lag time (peak of contraction-trough of deceleration) increased from 28 seconds (at 20 to 29 lost beats) to > 100 seconds with increase in deceleration area. Of patients with large decelerations 76% had a normal vaginal delivery. CONCLUSION: Large decelerations near term, present in up to 5% of patients with otherwise normal fetal heart rate and variation, are often associated with a fall in fetal heart rate variation characteristic of a change in sleep state, without ominous significance.

Female↗
PubMed1993

Sera from women with unexplained infertility inhibit both mouse and human embryo growth in vitro.

OBJECTIVES: To compare the effect of sera from women with reproductive disorders on the in vitro growth of mouse and human embryos up to the blastocyst stage and to determine the influence on human pregnancy outcome. DESIGN: The growth of mouse embryos and in vitro fertilized human embryos up to the blastocyst stage was compared in sera from women with unexplained infertility, and these results were correlated with pregnancy outcome. Also the growth of mouse embryos in sera from women with a history of recurrent abortions was correlated with their pregnancy outcome. PATIENTS, SETTING: Women with unexplained infertility were attending the IVF Unit at the John Radcliffe Hospital, Oxford, United Kingdom. Women with a history of recurrent abortions were attending the high risk pregnancy unit at the same hospital. MAIN OUTCOME MEASURES: Human embryo growth was monitored by daily morphological assessment and mouse embryo growth by both morphological assessment and tritiated thymidine uptake. RESULTS: In 15 women with unexplained infertility, poor mouse embryo development correlated with poor human embryo quality and impaired blastocyst formation when cultured in the same serum, as well as failure to achieve a pregnancy. In 11 women with a history of recurrent abortion, inhibition of mouse embryo growth correlated with unsuccessful pregnancy outcome. DISCUSSION: Assessment of both morphological development and cell proliferation in mouse embryos may be a useful test to determine the suitability of maternal sera for human IVF embryo culture, predicting pregnancy outcome and for categorizing women with reproductive disorders for future clinical management.

Abortion, Habitual↗
PubMed1993

The West Midlands epithelial ovarian cancer adjuvant therapy trial.

In a multicentre prospective randomized controlled trial, single agent cisplatinum was compared with whole abdomino-pelvic moving strip radiotherapy in the management of Stage IC-III epithelial ovarian cancer patients who had no macroscopic residual disease after primary surgery. Over a 6-year period 40 eligible patients were recruited, 15 of whom had Stage III disease. The overall 5-year survival was 60% with no significant survival difference between the treatment groups. Acute toxicity was common in both arms and six (11%) patients experienced significant long term disability.

Chemotherapy, Adjuvant↗
PubMed1993

Expression of the three endothelin genes and plasma levels of endothelin in pre-eclamptic and normal gestations.

1. Maternal vasoconstriction and fetal growth retardation are part of the syndrome of pre-eclampsia and are thought to be related to placental insufficiency. There is evidence to suggest that the powerfully vasoactive endothelin peptides might be involved in the pathogenesis. 2. The production of endothelins appears to be regulated mainly by modulation of mRNA levels, and they are thought to exert their effects locally, rather than systemically. Hence, the measurement of endothelin mRNA levels in tissues would be expected to reflect the activity of the endothelin systems. 3. RNAase protection assays, using specific antisense probes capable of distinguishing between the endothelin mRNA isoforms, have been used to examine the expression of the three endothelin genes in placental villous tissue, amniotic membrane and myometrium. Samples were taken from 15 pre-eclamptic women and from 14 women with normal gestations. Myometrium was taken at hysterectomy from five non-pregnant women as an additional control. Plasma concentrations of immunoreactive endothelin [endothelin-1, endothelin-2 and big endothelin (not distinguished)] were measured in samples taken concurrently from uterine vein and peripheral blood during surgery in ten patients. 4. The level of endothelin-1 mRNA in placental villous tissue was significantly higher in pre-eclamptic women (32 weeks gestation) than in control subjects (38 weeks gestation) (1.85 +/- 0.26 versus 0.52 +/- 0.09 arbitrary units, means +/- SEM, P < 0.001) and in gravid than in non-gravid myometrium (P < 0.001). Endothelin-2 was not expressed in villous tissue, but was expressed in amniotic membrane and myometrium, with relatively little difference between pre-eclamptic and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Obstetric and neonatal outcome in fetuses with absent end-diastolic velocities of the umbilical artery: a case-controlled study.

Absence of end-diastolic velocities (AEDV) is the most severe waveform abnormality detected by Doppler ultrasound examination of the umbilical artery. It is associated with fetal hypoxemia and acidemia. If AEDV predisposed to more neonatal complications, then it might be an indication for earlier delivery. This was investigated in 21 preterm fetuses with AEDV who were matched for gestational age at delivery with 21 with end-diastolic velocities. All fetuses were delivered electively before 36 weeks' gestation of mothers who were hypertensive. The fetal heart rate (FHR) variability, birthweight, and umbilical arterial blood pH were significantly lower in the AEDV group. However, the neonatal outcomes were similar except for less severe hyaline membrane disease and lower initial platelet counts in the AEDV group. At present, fetuses with umbilical arterial AEDV need not be delivered earlier than indicated by the FHR pattern, nor should neonatal management be altered on the basis of antenatal AEDV.

Acidosis↗