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Biomedical subjects

I Z MacKenzie

Publications and source records attributed to I Z MacKenzie.

At least 37 records · Page 2Linked to original sources
PubMed2000

Adrenomedullin is an autocrine regulator of endothelial growth in human endometrium.

Human endometrium is a mucosa served by a microvascular blood supply that involves benign angiogenesis under the control of ovarian steroids throughout reproductive life. Adrenomedullin is a multifunctional 52-amino acid peptide involved in numerous physiological and pathological processes, including angiogenesis, growth regulation, differentiation, vasodilation and smooth muscle relaxation. We have previously shown that adrenomedullin is present in the human uterus. To investigate further the role of adrenomedullin in human endometrial angiogenesis, a method for the isolation and culture of non-pregnant endometrial endothelium was developed. Enzymatic dispersion and 'Percoll' gradient centrifugation, followed by positive selection using Ulex europaeus agglutinin-coated immunomagnetic beads, yielded pure isolates of endothelium. The cells formed a typical 'cobblestone' monolayer within 5-7 days and expressed the classic endothelial markers, CD31 and von Willebrand factor. The presence of adrenomedullin immunoreactivity in endometrial endothelial cells was shown by immunohistochemistry both in vitro and in vivo. Adrenomedullin promotes growth of endothelial cells as measured by [methyl-(3)H] thymidine uptake. Adrenomedullin also induced cyclic AMP in endometrial endothelial cells. These results demonstrate, for the first time, that adrenomedullin is an autocrine growth factor for human endometrial endothelial cells and is thus involved in endometrial angiogenesis.

Adrenomedullin↗
PubMed2000

Decision to delivery intervals for assisted vaginal vertex delivery.

OBJECTIVE: To describe the time interval between decision for assisted vaginal delivery and the birth of the baby in different clinical circumstances. DESIGN: A prospective analysis of 225 consecutive women with a singleton fetal cephalic presentation in the second stage of labour requiring an operative vaginal delivery for various reasons. SETTING: A maternity unit in a district general hospital delivering more than 6,000 women annually. MAIN OUTCOME MEASURES: The decision to delivery interval and the immediate and short term maternal and neonatal outcomes according to indication for operative vaginal delivery. RESULTS: The mean (SD) decision to delivery interval was 34.4 minutes (28.3) with a range of 5 to 101 minutes. For those delivered because of suspected fetal distress, the interval of 26.5 minutes (14.0) was significantly shorter than for those performed without fetal distress 39.5 minutes (19.0) (P < 0.0001); for cases with fetal distress, forceps were significantly quicker at 23.3 minutes (14.3) than the ventouse 29.2 minutes (13.2) (P = 0.04). The longer the interval in cases of fetal distress the less favourable the condition of the neonate at birth, although this trend did not reach statistical significance and was not seen for deliveries expedited for other reasons. Perineal repair was required following 96% forceps deliveries compared with 87% ventouse (P = 0.015). Perineal trauma was not influenced by the interval between decision and delivery. CONCLUSIONS: If speed of delivery is important, use of forceps results in a quicker birth than use of the ventouse, without any compromise to the condition of the baby at delivery, and with similar rates of perineal trauma.

Adult↗
PubMed2000

Should tissue from pregnancy termination and uterine evacuation routinely be examined histologically?

OBJECTIVE: To assess the value of routine histological examination of tissue samples collected at termination of pregnancy in the first trimester and emergency surgical uterine evacuation. SETTING: The gynaecological department of a teaching hospital. DESIGN: Prospective study of women attending the gynaecological department in a 12-month period. PARTICIPANTS: All women undergoing a therapeutic first trimester medical or surgical abortion or an emergency surgical evacuation of a failed pregnancy, suspected incomplete spontaneous miscarriage or incomplete induced abortion. MAIN OUTCOME: Association of pre-operative clinical diagnosis and the post-operative histological result. RESULTS: Of 1,576 women studied, the histological report confirmed that products of conception were obtained in 1,465 (93%); in two women (0.13%) molar changes were reported confirming the preoperative diagnosis by ultrasound. Products of conception were not confirmed in the tissue specimens in 0.5% medical terminations, 5% surgical terminations, 10% evacuations following a previous evacuation, 12% evacuations for a failed pregnancy, and 19% evacuations for an incomplete miscarriage. In 87 women (6%), decidua was reported; two of these women had undergone an evacuation for an ultrasound diagnosis of spontaneous miscarriage, but in both a tubal ectopic pregnancy was subsequently diagnosed. CONCLUSION: There did not appear to be any obvious benefit from routine histological examination of tissue removed at termination of pregnancy or emergency uterine evacuation. The histological result was sometimes not consistent with the pre-operative diagnosis and may result in unnecessary further investigation and treatment unless due consideration is given to the clinical presentation.

Abortion, Induced↗
PubMed2000

Loss of myometrial oxytocin receptors during oxytocin-induced and oxytocin-augmented labour.

Oxytocin is used widely for the induction and augmentation of labour, but there is little information about the dynamics of oxytocin receptors in human myometrium during parturition, and the possible effect of oxytocin infusion. This information is important because G protein-coupled receptors, such as the oxytocin receptor, undergo desensitization after prolonged or repeated stimulation. The concentration of myometrial oxytocin receptors and the steady state of its mRNA were measured in patients undergoing Caesarean sections before or during spontaneous or induced labour. The concentration of receptors before labour was 477 (175-641) fmol mg(-1) protein (median, quartile range), and decreased to 140 (72-206; P < 0.05) and 118 (69-75; P < 0.01) fmol mg(-1) protein during prolonged oxytocin-augmented and oxytocin-induced labour, respectively. The corresponding oxytocin receptor mRNA concentrations decreased by 60- and 300-fold, respectively. The decrease in receptor binding and mRNA in women receiving oxytocin infusion indicates that homologous receptor desensitization occurs in vivo.

Analysis of Variance↗
PubMed2000

Expression of the hypoxically regulated angiogenic factor adrenomedullin correlates with uterine leiomyoma vascular density.

Uterine leiomyomas are the most prevalent benign tumor type in women of reproductive age and are one of the most common indications for hysterectomy. The expression of five angiogenic factors, adrenomedullin (ADM), vascular endothelial growth factor (VEGF), acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived endothelial cell growth factor/thymidine phosphorylase, were examined in 91 uteri collected throughout the menstrual cycle; 52 of which contained leiomyomata, and the remainder were normal controls. The microvascular density and endothelial proliferative indices were then determined for each of the uterine sections. ADM and VEGF were the most widely expressed angiogenic factors in the leiomyomas. Furthermore, the expression of ADM and VEGF in the endometrium and myometrium was up-regulated in leiomyoma-bearing uteri compared with controls. Although acidic fibroblast growth factor and basic fibroblast growth factor were expressed in leiomyomas and endometrium in all of the uterine samples examined, they were only expressed in the myometrium of leiomyomata-bearing uteri. Endothelial proliferation in leiomyomas was statistically greater than that of the myometrium and endometrium, both within and between uteri (P < 0.05). The vascular density in the myometrium but not the endometrium was significantly increased in leiomyoma-containing uteri (P < 0.05). Expression of ADM alone correlated directly with vascular density and endothelial cell proliferation index in leiomyomas and myometrium and may account for the high vascularity found in leiomyomas and the myometrium of leiomyoma-bearing uteri. As such, ADM is identified as a novel target for antiangiogenic therapy of these benign, clinically problematic uterine tumors.

Adrenomedullin↗
PubMed1999

Gestational regulation of granulocyte-colony stimulating factor receptor expression in the human placenta.

A number of cytokines and their receptors are abundantly expressed at the materno-fetal interface and are thought to have a function in the regulation of placentation. Granulocyte-colony stimulating factor (G-CSF) is expressed by stromal cells in both placental tissue and maternal decidua throughout placentation. In this study, we examined the expression of placental G-CSF receptor (G-CSFR) mRNA and protein throughout gestation by ribonuclease protection assays, Western blotting, and immunohistochemistry. The major placental form of G-CSFR mRNA, corresponding to a membrane-bound form of the protein, was present in first-trimester placental tissues; levels decreased in second- and were highest in third-trimester placental tissues. Two placental G-CSFR molecules, 120 kDa and 150 kDa, were detected in first- and third-, but not second-, trimester tissues. The level of the 150-kDa G-CSFR was greater in the third- than in first-trimester samples. These differences were irrespective of whether or not the patients had received prostaglandin E1 analogues, prostaglandin E1 analogues and oxytocin, oxytocin alone, or mifepristone before labor. We demonstrated by immunohistochemistry that interstitial cytotrophoblast in first- and second-trimester decidual tissue and cytotrophoblast in term fetal membranes express G-CSFR. These data demonstrate that the expression of specific forms of placental G-CSFR is strictly cell type- and developmental stage-specific, and they suggest that G-CSFR may be important in decidual invasion of cytotrophoblast and in trophoblast function during placentation.

Abortifacient Agents, Steroidal↗
PubMed1999

Routine antenatal Rhesus D immunoglobulin prophylaxis: the results of a prospective 10 year study.

OBJECTIVE: To assess the clinical and financial impact, and identify the problems, of providing routine antenatal RhD immunoglobulin prophylaxis for Rhesus D negative nulliparae. DESIGN: A retrospective (1980-1986) and prospective (1987-1996) comparison between two similar populations, one population with nulliparae offered routine RhD immunoglobulin 500 IU prophylaxis at 28 and 34 weeks of gestation part way through the study period, and the other population not offered prophylaxis at any time. SETTING: Obstetric units in two counties (three health districts) with similar annual numbers of maternities and the Regional Blood Transfusion Service antenatal serology laboratory. PARTICIPANTS: Non-sensitised Rhesus D negative pregnant nulliparae. INTERVENTIONS: Intramuscular RhD immunoglobulin 500 IU at 28 and 34 weeks of gestation to eligible women booked for confinement in one county; the intervention not offered in the other county. MAIN OUTCOME MEASURES: 1. Rhesus D sensitised second pregnancy rate; 2. success in providing prophylaxis to eligible women; 3. serology laboratory activity changes; 4. potential savings from the prophylaxis programme. RESULTS: Prophylaxis significantly reduced iso-immunisation in the next pregnancy when compared with historical (OR 0.28, CI 0.14-0.53; P < 0.0001) and contemporary controls (OR 0.43, CI 0.22-0.86; P = 0.02). However, success at achieving comprehensive prophylaxis was disappointing, with only 89% of eligible women receiving the first injection, 74% both injections, and for only 29% were both at the correct gestation. Fifty-two percent of women delivered after 40 weeks of gestation, beyond the period of adequate prophylaxis protection. The savings in antenatal interventions, neonatal care and possible long term ill-health that result from very preterm birth should be considerable. CONCLUSION: Routine prophylaxis for nulliparae significantly reduces the incidence of sensitised next pregnancies with consequent savings, and its adoption nationwide should be encouraged. A programme offering antenatal prophylaxis for all Rhesus D negative women is unlikely to be economic. Improvement in uptake of prophylaxis is needed; alternative administration strategies should be explored.

Female↗
PubMed1997

Recombinant human relaxin as a cervical ripening agent.

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of recombinant human relaxin (rhRIx) as a cervical ripening agent in women with an unfavourable cervix before induction of labour at term. DESIGN: A multi-centre, double-blind, placebo-controlled trial performed in Edinburgh, Glasgow and Oxford. Women were treated with 0, 1, 2 or 4 mg of rhRIx in a gel vehicle administered intravaginally. Analysis of variance tests were performed on all continuous variables, and Cochran Mantel-Haenszel tests employed for all discrete variables. PARTICIPANTS: Ninety-six women at 37 to 42 weeks of gestation with a singleton pregnancy and a modified Bishop score of < or = 4 were recruited. RESULTS: There was no significant difference in the change in modified Bishop score between the four treatment groups. The lengths of the first and second stages of labour were similar in all 4 groups. PGE2 and oxytocin requirements were similar in all groups, as was the mode of delivery. There was no evidence that relaxin was absorbed systemically when given in this way. CONCLUSION: Recombinant human relaxin 1 to 4 mg, administered as an intravaginal gel, has no effect as a cervical ripening agent before induction of labour at term.

Administration, Intravaginal↗
PubMed1997

Randomised trial of one versus two doses of prostaglandin E2 for induction of labour: 1. Clinical outcome.

OBJECTIVE: To compare the outcome of induction of labour using a single versus two doses of prostaglandin E2 vaginal gel. DESIGN: Prospective randomised trial comparing a single dose of prostaglandin E2 2 mg vaginal gel in the evening with two doses of prostaglandin E2 (2 mg), the second being given after six hours if labour had not started or the cervix was still unripe. Amniotomy and oxytocin titration were performed when necessary for both protocols. Nulliparae and multiparae were analysed separately by treatment intention. SETTING: A maternity unit in a district general hospital annually delivering > 6000 women. PARTICIPANTS: Nine-hundred and ninety-five women with viable singleton pregnancies and cephalic presentation at term without previous history of caesarean section who were advised to have labour induced with prostaglandins. MAIN OUTCOME MEASURES: Need for formal amniotomy and oxytocin augmentation, use of epidural analgesia, rate of intrapartum interventions, mode of delivery and neonatal condition at birth. RESULTS: For multiparae two prostaglandin doses resulted in a significant reduction in the need for formal amniotomy (15% vs 30%) and oxytocin augmentation (28% vs 38%) compared with those receiving a single dose; there was no significant difference for nulliparae. Other interventions during labour, length of labour, and mode of delivery were similar in both protocols. Failed induction occurred only in nulliparae and was similar in both protocols (1%). There was no discernible difference in fetal or neonatal outcome although passage of meconium was more common in labour if two doses had been given, as was neonatal admission to the special care baby unit. CONCLUSIONS: There was little clinical benefit from inducing labour with two doses of prostaglandin E2 at a six-hour interval, compared with a single dose. There may be financial advantages with a two-dose regimen.

Administration, Intravaginal↗
PubMed1997

Randomised trial of one versus two doses of prostaglandin E2 for induction of labour: 2. Analysis of cost.

OBJECTIVE: To compare the impact upon maternity unit resources and finances of two protocols for induction of labour using prostaglandins. DESIGN: A prospective randomised trial comparing a single dose of prostaglandin E2 (2 mg) in the evening with two doses of prostaglandin E2 (2 mg), the second being given after six hours if labour had not started or the cervix was still unripe, followed if necessary by formal induction of labour by amniotomy and oxytocin infusion 14 to 20 hours after the initial prostaglandin E2 dose. Outcome for nulliparae and multiparae were analysed separately, by treatment intention. SETTING: A maternity unit in a district general hospital delivering > 6000 women annually. PARTICIPANTS: Nine hundred and fifty-five women with viable singleton pregnancies and cephalic presentation at term without previous history of caesarean section who were advised to have labour induced with prostaglandins. MAIN OUTCOME MEASURES: Costs incurred in managing all aspects of labour, including time spent on the antenatal ward and, in the delivery unit; costs associated with formal induction, augmentation of labour and epidural analgesia; costs of intrapartum maternal morbidity, mode of delivery and immediate neonatal care. Costs of postpartum hospital stay were estimated from unit statistics. RESULTS: The overall mean cost of induction of labour was Pounds 5.00 and Pounds 7.22 less per woman for nulliparae and multiparae, respectively, if the two dose regimen was used. The main reason for the differences was due to delivery suite costs from the slightly greater rate of assisted deliveries in the single treatment groups. In contrast, costs for neonatal care were marginally lower if only one prostaglandin dose was used. CONCLUSIONS: The increased drug costs providing two prostaglandin E2 doses when required were off-set by reductions in the costs of other intrapartum interventions for both nulliparae and multiparae. The advantages of less time spent on the antenatal ward for multiparae when two prostaglandin E2 doses were used may be eliminated if amniotomy and oxytocin infusion was commenced six hours after the initial prostaglandin dose had been given if labour had not started.

Dinoprostone↗
PubMed1995

Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies.

The increase in survival of very preterm babies during the 1980s was accompanied by a sharp increase in the rate of cerebral palsy in this group. The relation between antenatal and intrapartum factors and cerebral palsy in such babies has not been well defined. To identify adverse and protective antenatal and intrapartum factors we undertook a case-control study of 59 very preterm babies who developed cerebral palsy, identified from a population-based register, and 234 randomly selected controls. The frequency of cerebral palsy decreased with increasing gestational age and birthweight. Antenatal complications occurred in 215 (73%) of the women with preterm deliveries. Factors associated with an increased risk of cerebral palsy after adjustment for gestational age were chorioamnionitis (odds ratio 4.2 [95% CI 1.4-12.0]) prolonged rupture of membranes (2.3 [1.2-4.2]), and maternal infection (2.3 [1.2-4..5]). Pre-eclampsia was associated with a reduced risk of cerebral palsy (0.4 [0.2-0.9]), as was delivery without labour (0.3 [0.2-0.7]). There was no increased risk of cerebral palsy with intrauterine growth retardation (1.0 [0.9-1.1]). The effect of rigorous management of adverse antenatal factors on the frequency of cerebral palsy in very preterm babies should be tested in randomised controlled trials.

Apgar Score↗