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Biomedical subjects

I Z MacKenzie

Publications and source records attributed to I Z MacKenzie.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Temporary reappearance of sperm 12 months after vasectomy clearance.

OBJECTIVES: To determine the incidence of positive semen analysis 12 months after vasectomy clearance. SUBJECTS AND METHODS: A prospective study was undertaken, starting in 1990, of men undergoing vasectomy. Azoospermia was confirmed by two successive semen analyses 16 weeks after vasectomy. One year later a further sample was analysed for the presence of sperm. RESULTS: Of 1000 men who provided a sample for analysis, six men (0.6%) have had positive semen analyses 1 year after the initial tests showed azoospermia. In all six the sperm count was <10,000 per mL. Five of the six men produced a repeat sample 1 month later which, in all five cases, showed azoospermia. No pregnancies have been reported to date. CONCLUSION: Transitory reappearance of sperm following successful vasectomy occurs in about 0.6% of men. This incidence is 18 times greater than the reported pregnancy rate following successful vasectomy.

Humans↗
PubMed1995

The mortality and morbidity associated with umbilical cord prolapse.

OBJECTIVE: To examine the management of cord prolapse and its morbidity and mortality. DESIGN: Retrospective study of consecutive babies born after cord prolapse, identified using the Oxford Obstetric Data System, and those with registered handicap, identified by the Oxford Region Register of Early Childhood Impairments. SETTING: District maternity hospital managing more than 6000 deliveries annually. SUBJECTS: One hundred and thirty-two babies born after the identification of cord prolapse in the John Radcliffe Hospital between January 1984 and December 1992. MAIN OUTCOME MEASURES: Survival rates, condition at birth assessed by Apgar scores at 1 and 5 minutes and blood gas values on cord blood samples, and incidence of major handicap at three years of age. RESULTS: The incidence of cord prolapse was 1 in 426 total births. There were six stillbirths and six neonatal deaths. One baby died as a result of birth asphyxia. The uncorrected perinatal mortality rate was 91 per 1000. Of 120 survivors, only one baby was known to suffer a major neurological handicap. Electronic cardiotocographs aided the diagnosis of cord prolapse in 41% of cases. Apgar scores were better with a shorter diagnosis to delivery interval, but cord gas results did not correlate well with Apgar scores or the diagnosis to delivery interval. CONCLUSIONS: Cord prolapse occurs with a relatively stable incidence in this population irrespective of changes in obstetric practices. Despite the high incidence of ominous cardiotocographs, low Apgar scores and acidaemia on blood gas analysis, the fetal outcome is not as poor as might be expected and mortality is predominantly attributable to congenital anomalies and prematurity rather than birth asphyxia.

Cardiotocography↗
PubMed1995

Gastrointestinal and pancreatic hormones in the human fetus and mother at 18-21 weeks of gestation.

Several gastrointestinal hormones appear to play an important developmental role in the newborn, particularly in preterm neonates. Although the cells producing these peptides develop towards the end of the first trimester, fetal secretion of these regulatory peptides has not hitherto been demonstrated. Using samples collected by fetoscopy at 19-21 weeks of gestation we have measured concentrations of several gastrointestinal and pancreatic hormones. Maternal venous and amniotic fluid hormone concentrations were measured simultaneously. Concentrations of the pancreatic hormones, insulin, glucagon and pancreatic polypeptide (PP) were similar in fetal and maternal blood. Gastrin and motilin were present in the fetal circulation but at about 30% (p < 0.05) and 60% (p < 0.01) of the maternal levels, respectively. In contrast, enteroglucagon concentrations were more than twofold higher in the fetal circulation compared with maternal levels (p < 0.05). Concentrations of gastric inhibitory polypeptide (GIP) in fetal blood were higher than levels in maternal blood but not significantly. Concentrations of GIP (p < 0.001) were higher in the amniotic fluid than the fetal circulation. Gastrin and glucagon levels were similar in amniotic fluid and fetal blood. In contrast, PP and motilin were present in amniotic fluid, but at lower concentrations than in fetal blood. Enteroglucagon was not detectable in amniotic fluid. In conclusion, several alimentary hormones are secreted in the fetus at midterm. Since these peptides have trophic, secretory and motor effects on the gut, it is likely that these regulatory peptides are involved in the functional development of the fetal intestine.

Amniotic Fluid↗
PubMed1995

Effects of oestradiol and tamoxifen on oxytocin-induced phospholipase C activation in human myometrial cells.

The role of oestradiol in the control of uterine responsiveness to oxytocin was investigated by measuring oxytocin-induced phospholipase C activation in [3H]inositol-labelled cultured human myometrial cells. Addition of oestradiol to steroid-free culture medium (10% (v/v) fetal calf serum treated with dextran-coated charcoal in phenol red-free medium) enhanced formation of inositol phosphates and this effect was completely abolished by the anti-oestrogen tamoxifen. The inhibitory effect of tamoxifen on oxytocin-induced phospholipase C activation occurred in both steroid-free and complete culture medium; it was time- and concentration-dependent and was only partly reversed by oestradiol. When phospholipase C was activated with PGF2 alpha or fluoroaluminate instead of oxytocin, oestradiol and tamoxifen had the same stimulatory and inhibitory effects, respectively. The inhibitory effect of tamoxifen could not be prevented by treating the cells with pertussis toxin. Moreover, the effect of tamoxifen was not mediated by inhibition of protein kinase C, since the use of staurosporine (a protein kinase inhibitor) resulted in potentiation of phospholipase C activation by oxytocin. Both oestradiol and tamoxifen increased [3H]inositol incorporation into cellular lipids and cell proliferation. These results suggest that oestradiol enhances myometrial responsiveness to oxytocin and other agonists by facilitating phospholipase C activation at a post-receptor level. This effect is antagonized by tamoxifen; however, tamoxifen also has oestrogen-independent inhibitory effects.

Alkaloids↗
PubMed1994

Analysis of limb reduction defects in babies exposed to chorionic villus sampling.

In 1991 we reported a cluster of babies with limb abnormalities and suggested that chorionic villus sampling (CVS) was aetiologically associated with these defects. To address the issue more objectively, we have assessed reported limb reduction defects in 75 babies exposed to CVS in utero. 13 babies had an absent limb or a defect through the humerus or femur; 9 had defects through the radius or tibia; 22 defects of the carpus, tarsus, metacarpus, or metatarsus; 25 defects of the digits; and 6 defects of the terminal phalanx or nail only. There was a strong correlation between the severity of the defects and the duration of gestation when CVS was done. The median gestational age at CVS ranged from 56 (range 49-65) postmenstrual days for the most severe category to 72 (51-98) days for the least severe. The relation was seen for both isolated limb defects and for cases with oromandibular-limb hypogenesis syndromes. This relation is further evidence that CVS has an aetiological role in some limb reduction anomalies.

Abnormalities, Multiple↗
PubMed1994

A prospective, double-blind, randomized comparison of prophylactic intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, and intravenous oxytocin, 20 units, for the control of blood loss at elective cesarean section.

OBJECTIVE: Our purpose was to compare intramyometrial 15-methyl prostaglandin F2 alpha with intravenous oxytocin for controlling blood loss at elective cesarean section. STUDY DESIGN: A double-blind, randomized trial was performed with intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, or intravenous oxytocin, 20 U, in 60 women undergoing elective lower segment cesarean section at 36 to 41 weeks' gestation. Subjective assessment of the operative blood loss and early lochial discharge and objective change in hemoglobin and hematocrit before and 24 hours after delivery and the incidence of side effects were compared by nonparametric statistical tests. RESULTS: The mean estimated blood loss was similar in both groups, with 645 ml (SD 278, range 400 to 1500) in the 15-methyl prostaglandin F2 alpha group compared with 605 ml (SD 303, range 200 to 1750) in the oxytocin group. The mean fall in hemoglobin and hematocrit was greater in the 15-methyl prostaglandin F2 alpha group than in the oxytocin group, 0.98 gm/dl (SD 0.95) versus 0.65 gm/dl (SD 0.79) for hemoglobin and 2.58% (SD 2.96) versus 2% (SD 2.96) for hematocrit. None of these differences reached statistical significance. There were no differences in side effects and lochial discharge between the treatment groups. In both groups there was a decrease of approximately 1% in maternal arterial oxygen saturation. CONCLUSION: Routine intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, does not offer any obvious advantage over intravenous oxytocin, 20 U, in reducing operative blood loss at elective lower-segment cesarean section.

Adult↗
PubMed1994

Effect of oxytocin antagonists on the activation of human myometrium in vitro: atosiban prevents oxytocin-induced desensitization.

OBJECTIVE: Our purpose was to investigate whether the sensitivity of myometrial cells to oxytocin is affected by prolonged exposure to oxytocin antagonists. STUDY DESIGN: Tissue slices or cultured myometrial cells were exposed to peptides in vitro. Myometrial activation was studied by measuring the formation of inositol phosphates and the changes in intracellular calcium. Oxytocin binding was measured by saturation analysis. RESULTS: Atosiban and related peptides inhibited oxytocin-induced myometrial activation as pure antagonists (inhibition constant 10 nmol/L) but had no effect on prostaglandin E2-induced activation. Long-term (> or = 24 hours) exposure to atosiban had no residual effect on oxytocin sensitivity. However, long-term exposure to oxytocin resulted in homologous desensitization and loss of oxytocin receptors. Oxytocin-induced desensitization was prevented by coincubation with atosiban. CONCLUSIONS: Atosiban is a pure oxytocin antagonist and has a specific, reversible effect on myometrial cells in vitro. Its potential use for the management or even prevention of idiopathic preterm labor or to reverse uterine hypertony during oxytocin-induced labor should be tested in controlled clinical trials.

Calcium↗
PubMed1993

Diagnostic dilatation and curettage: is it used appropriately?

OBJECTIVE: To determine patterns of use of dilatation and curettage in Britain as compared with those in the United States; to examine variations in utilisation rates within one regional health authority. DESIGN: Analysis of routinely collected hospital inpatient statistics. SETTING: Statistics for England, Scotland, and the United States; local statistics for Oxford region. SUBJECTS: All inpatient episodes in which dilatation and curettage was performed but excluding those related to pregnancy. RESULTS: Dilatation and curettage rates remained stable in Britain between 1977 and 1990, whereas in the United States they declined dramatically. In 1989-90 the rate was 71.1 per 10,000 women in England as compared with only 10.8 per 10,000 in America. In 1989, 6936 women underwent diagnostic dilatation and curettage in the Oxford region, making it the most common elective operation. A total of 2726 (39%) of these women were under 40. There was a more than twofold variation in usage of the procedure among district health authorities within the region and even greater variation in rates in women under 40. The proportion of patients treated as day cases in the district general hospitals ranged from 22% to 82%. CONCLUSIONS: Dilatation and curettage may frequently be used inappropriately. The considerable variations in usage of dilatation and curettage internationally and nationally indicate differences in clinical perception of its appropriateness. This makes it suitable for audit. In developing guidelines it will be important to agree on the most appropriate patients and the relative merits of alternative methods of endometrial sampling. Probably this could result in considerable cost savings at no risk and possibly some benefit to patients.

Adolescent↗