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I Z MacKenzie

Publications and source records attributed to I Z MacKenzie.

At least 19 recordsLinked to original sources
PubMed2006

The kinetics of routine antenatal prophylactic intramuscular injections of polyclonal anti-D immunoglobulin.

OBJECTIVE: To observe the pharmacokinetics of intramuscular anti-D immunoglobulin (IgG) given for routine antenatal prophylaxis. DESIGN: Prospective observational study. SETTING: Maternity unit and antenatal serology laboratory in a district teaching hospital. POPULATION: Forty-five rhesus-D-negative pregnant women not sensitised to RhD. METHODS: Serial serum quantitations of anti-D IgG following the intramuscular injections of anti-D IgG 100 microg (500 IU) at 28 and 34 weeks of gestation. Anti-D IgG concentrations were assayed with the RFA-300 continuous flow analyser. MAIN OUTCOME MEASURES: The kinetic profile and duration of detectable anti-D IgG in maternal serum following the first and second injections of anti-D IgG. RESULTS: For the 43 women in whom serial data were collected, there were no detectable differences between pregnancies with an RhD-positive (26) or -negative (17) fetus. Maximum IgG concentrations were detected two to five days following the first anti-D IgG injection and ranged between 0 and 28 ng/mL. Only 30% of women still undelivered at 40 weeks of gestation had detectable IgG at 2 ng/mL or greater. There was a significant relationship between higher maximum values and low maternal surface body area (R2 = 0.204, P = 0.002), but this did not influence duration of persistent IgG. CONCLUSION: Using previously published data, 70% women are not adequately protected with anti-D IgG 12 weeks after the first prophylactic injection. Despite this, previous clinical results suggest that the antenatal prophylaxis schedule used provides adequate protection and that the recommendation for the lowest concentration of protective anti-D IgG antibody levels currently in use is probably overestimated.

Adult↗
PubMed2006

Does a first trimester dating scan using crown rump length measurement reduce the rate of induction of labour for prolonged pregnancy? An uncompleted randomised controlled trial of 463 women.

OBJECTIVE: To evaluate the effect of a first trimester ultrasound dating scan on the rate of induction of labour for prolonged pregnancy. DESIGN: Randomised controlled trial to include 400 women in each arm of the trial. SETTING: Participating general practices and a district general teaching hospital. POPULATION: Women attending their general practitioner in the first trimester to confirm pregnancy, in whom a first trimester ultrasound scan was not indicated. METHODS: Women randomised to the study group (scan group) underwent an ultrasound dating scan between 8 and 12 weeks, measuring crown-rump length. The estimated date of delivery (EDD) was changed if there was a discrepancy of more than 5 days from the gestation, calculated from the last menstrual period (LMP). For the remaining women (no-scan group), gestation was determined using the LMP. MAIN OUTCOME MEASURES: The rate of induction of labour for prolonged pregnancy. RESULTS: Due to circumstances beyond the researchers' control, recruitment was abandoned when 463 women had been enrolled. The EDD was adjusted in 13 (5.7%) women in the scan group and in 2 (0.9%) in the no-scan group. There was no difference in the rate of induction for prolonged pregnancy between the scan (19 [8.2%]) and the no-scan (17 [7.4%]) groups (relative risk 1.10; 95% CI 0.59-2.07). CONCLUSIONS: Acknowledging the reduced numbers recruited for study, it is concluded that there is no evidence that a first trimester ultrasound dating scan reduces the rate of induction of labour for prolonged pregnancy and may result in a more expensive healthcare strategy.

Adult↗
PubMed2006

Compliance with routine antenatal rhesus D prophylaxis and the impact on sensitisations: observations over 14 years.

Documented routine antenatal anti-D prophylaxis was given to 90% and 81-87% of eligible women at 28 and 34 weeks of gestation, respectively, during the early 1990s and early 2000s. With increasing experience and education, a significant improvement in the timing of the first (OR 0.26, 95% CI 0.16-0.41: P < 0.0001) and second injections (OR 0.40, 95% CI 0.26-0.61: P < 0.0001) occurred during the latter period. Despite these improvements, there was no reduction in the sensitisation rate at 0.4%. However, this low rate occurred despite significant proportions of women delivering more than 42 days after the second injection. Fifteen of the 16 sensitised women had received routine antenatal prophylaxis.

Female↗
PubMed2003

Cesarean section on demand.

The safety of cesarean section has improved dramatically over the past 50 years. During the past 20 years a greater awareness of and discussion about the symptomatic morbidity that can result for women following vaginal delivery has occurred and women's expectations for the outcome of pregnancy for them and their babies has increased. A culture of choice has been promoted in recent years, but contrary to the anticipated demand for less obstetric intervention by those promoting choice, there has been an increase in demand for delivery by cesarean section rather than the reverse. With the balance in favor of benefit for the baby from delivery by cesarean section, it is now difficult to sustain the argument favoring vaginal delivery rather than planned cesarean section, using maternal morbidity and mortality statistics. A critical evaluation of the costs indicates that there are probably few grounds for denying women their request for cesarean section for economic reasons. It seems likely, therefore, that in the near future those advising women on the options for delivery will need to ensure that the risks of vaginal delivery are explained as well as those for planned cesarean section.

Cesarean Section↗
PubMed2003

Indications for caesarean section in a consultant obstetric unit over three decades.

In this paper, we aimed to identify changes in the indications for and timing of caesarean section over 20 years. This involved a prospective data collection by clinical record analysis throughout the 12-month periods for 1976, 1986 and 1996. The study was carried out in the maternity unit of a large district teaching hospital. We studied all women delivered by caesarean section. Main outcome measures were rates for different indications for caesarean section for the populations served during each of the 3 years. Analysis of 1819 caesarean sections showed an increasing rate, from 6.7% in 1976 to 14.2% in 1996. The proportion of planned antepartum deliveries remained constant at 54%, with previous caesarean section given as the main indication in 1976 (55%) and 1986 (49%) and maternal request in 1996 (23%). Caesarean section for intrapartum fetal distress doubled over the study period, with little evidence of improved neonatal or long-term outcome. Caesarean section for failed labour induction and failed first- and second-stage progress all increased and for failed assisted delivery increased threefold. Caesarean section with a singleton breech presentation increased from 30% to 88% and for twin pregnancies from 13% to 47%. The rate of caesarean section for women delivered previously by section remained unaltered at 56%. The proportion of pregnancies delivered by caesarean section increased for virtually all indications. Consumer expectation has encouraged a more ready use of section, with maternal choice being the most frequent indication in 1996.

Adult↗
PubMed2003

'Two week wait' standards for suspected gynaecological malignancy. On target, but missing the point?

OBJECTIVE: To assess the two-week rapid access referral system for UK general practitioners introduced in April 2000 for women suspected of having a gynaecological cancer. STUDY DESIGN: An audit of details of women referred between 1st April 2000 and 31st March 2003 via the two-week rapid access system to one gynaecological consultant who performs gynaecological oncology surgery at the John Radcliffe Hospital, Oxford. MAIN OUTCOME MEASURES: Information on waiting times, clinical indication (postmenopausal bleeding, suspicious pelvic mass, vulval lesions, or "other" symptoms including postcoital vaginal bleeding, suspicious lesions of the cervix or vagina), and subsequent diagnosis were recorded. Data on all other women in whom a diagnosis of a gynaecological malignancy was made during the same period following referral to the same consultant's routine gynaecological outpatient clinic were also collected. RESULTS: The target time of two weeks to see a consultant was met for 94% of women referred via the rapid access system. The response time declined slightly with increasing numbers of referrals. However, the majority of women with a gynaecological malignancy were not referred via the rapid access system. CONCLUSIONS: To accommodate the two-week rapid access referrals and achieve UK government targets, there was a reduction in appointments for routine outpatient referrals. However, as the majority of women with gynaecological malignancy presented via traditional referral routes, there is a danger that their diagnoses are being delayed.

Adult↗
PubMed2003

The usefulness of ultrasound assessment of amniotic fluid in predicting adverse outcome in prolonged pregnancy: a prospective blinded observational study.

OBJECTIVE: To determine whether a single ultrasound scan at or beyond 40 weeks of gestation to detect a single deepest pool of amniotic fluid <2 cm and amniotic fluid index (AFI) <5 cm is clinically useful in the prediction of subsequent adverse pregnancy outcome. DESIGN: A prospective double blind cohort study. SETTING: A university teaching hospital delivering approximately 6000 women annually. POPULATION: One thousand and five hundred and eighty-four pregnant women at or beyond 40 weeks of gestation. METHODS: Ultrasound assessment of liquor to detect the single deepest pool of amniotic fluid and derive the AFI at or after 40 weeks of gestation. MAIN OUTCOME MEASURES: Perinatal death, meconium aspiration, birth asphyxia, intervention in labour for fetal distress, a cord arterial pH <7 and admission to the neonatal unit. RESULTS: An AFI <5 cm but not a single deepest pool <2 cm was significantly associated with birth asphyxia or meconium aspiration. An AFI <5 cm was also significantly associated with caesarean section for fetal distress in labour, a cord arterial pH <7 at delivery and low Apgar scores. Despite there being a statistically significant association with adverse outcomes the sensitivity of AFI was low at 28.6%, 12% and 11.5% for major adverse outcome, fetal distress in labour or admission to the neonatal unit, respectively. CONCLUSIONS: The AFI is superior to a measure of the single deepest pool as an assessment of the fetus at or after 40 weeks but has a poor sensitivity for adverse pregnancy outcome. Routine use is likely to lead to increased obstetric intervention without improvement in perinatal outcomes.

Adult↗
PubMed2002

Wnt-7a is upregulated by norethisterone in human endometrial epithelial cells: a possible mechanism by which progestogens reduce the risk of estrogen-induced endometrial neoplasia.

Progestogens are added to oestrogen in hormone replacement therapy regimens to reduce the risk of endometrial cancer. We have performed in vitro studies analysing gene expression of isolated normal endometrial epithelia cells (NEE) treated with estradiol and the progestogen norethisterone acetate (NETA). We report here for the first time upregulation of the Wnt-7a gene by NETA in estrogen treated NEE. Wnt genes are a large family of developmental genes associated with cellular responses such as oncogenesis. We therefore suggest that upregulation of Wnt-7a may be associated with the antineoplastic effects of progestogens on the endometrium.

Cells, Cultured↗
PubMed2002

Tamoxifen induction of angiogenic factor expression in endometrium.

Tamoxifen is the current therapy of choice for patients with oestrogen receptor positive breast cancer, and it is currently under evaluation as a prophylactic for women at high risk of developing the disease. However, tamoxifen is also known to induce proliferative changes in the endometrium increasing the risk of developing endometrial hyperplasia, polyps and carcinoma. Angiogenesis is an intimate part of this process. For this reason, we have examined the expression of several well characterized angiogenic factors, namely, acidic and basic fibroblast growth factor, thymidine phosphorylase, vascular endothelial growth factor and adrenomedullin in both normal and tamoxifen exposed pre- and postmenopausal endometrium. Vascular density and endothelial proliferation index were also quantified. We found increased expression of acidic and basic fibroblast growth factor and adrenomedullin after treatment with tamoxifen mainly in premenopausal tissue. Vascular density was significantly increased in pre- but not post-menopausal endometrium (P=0.0018) following tamoxifen treatment. These results support the notion that angiogenesis is integral to the response to tamoxifen exposure, and is a potential target with which to block these side effects of tamoxifen.

Adrenomedullin↗
PubMed2002

Protease activated receptor-1 is down regulated by levonorgestrel in endometrial stromal cells.

Progestogens are used clinically for contraception, to control excessive menstrual bleeding and to oppose oestrogen in hormone replacement therapy. The use of intrauterine levonorgestrel (LNG) is however, associated with endometrial atrophy and decidualisation of the stroma. In this study, we aimed to identify genes whose expression is modulated by LNG either alone or in combination with progesterone. Thus endometrial stromal cells were stimulated with progesterone, LNG or LNG and progesterone. Poly-A RNA was isolated and used to probe expression arrays. The expression of a number of genes was altered on exposure to LNG or LNG and progesterone. Alteration of expression patterns was confirmed using semi-quantitative RT-PCR and western blot analysis. In particular, the protease activated receptor-1 (PAR-1) gene that encodes a receptor for thrombin was down regulated. This is the first demonstration that PAR-1 is down regulated by the progestogen LNG in human endometrium. Alteration in the expression levels of this receptor may affect both growth and haemostatic activity within the endometrium and may account for the observed morphological effects seen in users of intrauterine LNG delivery devices.

Down-Regulation↗
PubMed2002

In-vivo angiogenesis and progestogens.

BACKGROUND: Progestogens are used clinically for contraception, to control excessive menstrual bleeding, and to prevent estrogen-induced endometrial hyperplasia. A significant problem with progestogen-only methods of contraception is the induction of breakthrough bleeding. METHODS: The effects of different progestogens on angiogenesis were examined using two approaches. The mouse sponge angiogenesis assay employed direct delivery of the dose ranges achieved therapeutically. The angiogenic response to long-term intrauterine levonorgestrel exposure, compared with unexposed premenopausal endometrium, was also studied. RESULTS: In the mouse sponge assay, norethisterone and medroxyprogesterone acetate stimulated angiogenesis at all doses, but was dose-dependent for levonorgestrel and nomegestrol. Levonorgestrel stimulated angiogenesis in the dose range 100 pmol/l to 10 nmol/l, but not at higher doses. In contrast, nomegestrol acetate stimulated angiogenesis at high, but not low, doses. Expression of acidic and basic fibroblast growth factors, thymidine phosphorylase, vascular endothelial growth factor and adrenomedullin were unaltered in levonorgestrel-exposed endometrium compared with premenopausal controls. Vascular density was increased but endothelial proliferation reduced in levonorgestrel-exposed endometrium. CONCLUSIONS: This is the first report of the direct effects of a wide range of doses of different progestogens on angiogenesis; results suggest that vascular targeting may be an effective strategy to deal with progestogen-induced abnormal bleeding.

Administration, Intravaginal↗
PubMed2002

What is a reasonable time from decision-to-delivery by caesarean section? Evidence from 415 deliveries.

OBJECTIVE: To determine how long it takes from the decision to achieve delivery by non-elective caesarean section (DDI), the influences on this interval, and the impact on neonatal condition at birth. DESIGN: Twelve months prospective data collection on all non-elective caesarean sections. METHODS: Prospective collection of data relating to all caesarean sections in 1996 in a major teaching hospital obstetric unit was conducted, without the knowledge of the other clinicians providing clinical care. Details of the indication for section, the day and time of the decision and the interval till delivery were recorded as well as the seniority of the surgeon, and condition of the baby at birth. RESULTS: The mean time from decision-to-delivery for 100 emergency intrapartum caesarean sections was 42.9 minutes for fetal distress and 71.1 minutes for 230 without fetal distress (P < 0.0001). For 22 'crash' sections the mean time from decision-to-delivery was 27.4 minutes; for 13 urgent antepartum deliveries for fetal reasons it was 124.7 minutes and for 21 with maternal reasons it was 97.4 minutes. The seniority of the surgeon managing the patient did not appear to influence the interval, nor did the time of day or day of the week when the delivery occurred. Intrapartum sections were quicker the more advanced the labour, and general anaesthesia was associated with shorter intervals than regional anaesthesia for emergency caesarean section for fetal distress (P < 0.001). Babies born within one hour of the decision tended to be more acidaemic than those born later, irrespective of the indication for delivery. Babies tended to be in better condition when a time from decision-to-delivery was not recorded than those for whom the information had been recorded. CONCLUSION: Fewer than 40% intrapartum deliveries by caesarean section for fetal distress were achieved within 30 minutes of the decision, despite that being the unit standard. There was, however, no evidence to indicate that overall an interval up to 120 minutes was detrimental to the neonate unless the delivery was a 'crash' caesarean section. These data thus do not provide evidence to sustain the recommendation of a standard of 30 minutes for intrapartum delivery by caesarean section.

Adult↗
PubMed2001

A comparative study of surgical and medical procedures: 932 pregnancy terminations up to 63 days gestation.

The aim of this retrospective study was to compare the efficacy and complications associated with early medical and surgical pregnancy termination. The study population comprised 932 consecutive women undergoing pregnancy termination at gestations of 63 days or less. There were no age or parity differences between the study groups. Medical termination was performed with mifepristone 200 mg orally and misoprostol 800 microgram vaginally; surgical aspiration termination was performed under general anaesthesia. Outcome measures were: surgical curettage for presumed retained products of conception; ongoing pregnancy; and planned and emergency review in the unit. Early medical and surgical termination were associated with a 90.2 and 94.5% complete abortion rate respectively (P = 0.025). The complete abortion rate with medical termination decreased significantly with increasing parity; no such relationship with surgical abortion was found. Women of parity three or more were less likely to have a complete abortion following a medical (83.3%) compared to surgical procedure (97.7%) (P = 0.028). The ongoing pregnancy rate was 0.9% with medical and 0.5% with surgical termination (P = NS). Medical termination was associated with a lower complete abortion rate than surgical termination, particularly for women of higher parity. However, early medical termination allows over 90% of women to avoid the risks of surgical instrumentation of the uterus and anaesthesia.

Abortifacient Agents↗
PubMed2001

Morbidity of first trimester aspiration termination and the seniority of the surgeon.

Vacuum aspiration is a safe, acceptable, and efficacious method of first trimester pregnancy termination. The success and complication rates are thought to be partially dependent on operator experience and gestation. We examined this further by studying the outcome of 828 consecutive surgical abortions up to 13 weeks gestation in our hospital. The following outcomes were measured: surgical curettage for presumed retained products of conception; continuing pregnancy; uterine perforation; pelvic sepsis requiring intravenous antibiotics; and blood transfusion required. The complete abortion rate was 94.6% and the rate of continuing pregnancy 0.24%. There was a significant relationship between efficacy and seniority of the surgeon; consultants, senior registrars, registrars, and senior house officers had complete abortion rates of 97.8, 92.8, 94.7, and 88.4% respectively (P = 0.039). Parity did not affect efficacy. Terminations at 12-13 weeks gestation were associated with a significantly lower complete abortion rate. The rates of uterine perforation, blood transfusion, pelvic sepsis requiring intravenous antibiotics, and overnight hospital admission were 0.24, 0, 0.97, and 1.69% respectively. Thus, the only significant factors affecting outcome of surgical abortion are grade of operating surgeon or terminations performed at later gestations of 12-13 weeks. It is vital that physicians performing surgical terminations are adequately trained.

Abortion, Induced↗
PubMed2001

Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus.

The calcitonin receptor-like receptor (CRLR) can function as a receptor for either calcitonin gene-related peptide (CGRP) or adrenomedullin (AM), depending upon co-expression with members of a novel family of receptor activity-modifying proteins (RAMP). RAMP1 presents the CRLR at the cell surface as a CGRP/AM receptor. RAMP2- and RAMP3-transported CRLR receptors act as AM-specific receptors. However, it is still unknown if this signalling system operates in vivo. Of particular interest is the uterus, where both peptides and their binding sites are known to be present and where both mitogenic and vasodilatory responses to AM and CGRP have been demonstrated. In this study, we examined whether CRLR and RAMP are co-expressed in the same populations of cells in human uterine tissue. Analysis by in-situ hybridization and immunocytochemistry revealed a heterogeneous and cell type-specific distribution of components of this AM/CGRP signalling system. Adrenomedullin mRNA was expressed and evenly distributed across all cell types. CRLR mRNA was predominantly found in blood vessels. RAMP1 expression was specific to myometrial myocytes and vascular smooth muscle cells in uterine arteries. RAMP2 and RAMP3 mRNA were not detectable by in-situ hybridization. The pattern of differential and cell-specific expression of CRLR and RAMP suggests the involvement of CRLR/RAMP1 in the processes of vasodilation, smooth muscle relaxation and angiogenesis in response to AM and CGRP in the human uterus, but also indicates that other receptors may be implicated.

Adrenomedullin↗
PubMed2001

Secondary postpartum haemorrhage: incidence, morbidity and current management.

OBJECTIVE: To determine the incidence, risk factors, presentation, treatment and morbidity associated with secondary postpartum haemorrhage. DESIGN: Analysis of 132 consecutive women presenting with secondary postpartum haemorrhage occurring over a three-year period. SETTING: The maternity unit in a district general teaching hospital serving an annual delivery rate of around 6500 women. MAIN OUTCOME MEASURES: Factors associated with the cause of the haemorrhage and the resulting morbidity. RESULTS: Most women presented during the second week after delivery. A history of primary postpartum haemorrhage (OR 9.3; 95% CI 6.2-14.0) and manual removal of placenta (OR 3.5; 95% CI 1.6-7.5) were the only significant risk factors identified. There was a high associated morbidity, with 84% requiring hospital admission, 63% surgical evacuation, 17% blood transfusion, with three women suffering a uterine perforation, one managed by hysterectomy. In women undergoing evacuation only, 37% had retained placental tissue confirmed after surgery; pre-operative ultrasound examination did not provide a better discrimination over clinical assessment for this finding. CONCLUSIONS: Secondary postpartum haemorrhage occurs in just under 1% of women, is associated with primary postpartum haemorrhage and retained placenta, and may result in significant maternal morbidity. This problem deserves more attention than it has received in recent years.

Blood Transfusion↗