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Biomedical subjects

I Z MacKenzie

Publications and source records attributed to I Z MacKenzie.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Anti-D concentrations in fetal and maternal serum and amniotic fluid in rhesus allo-immunised pregnancies.

OBJECTIVE: To investigate the relation between anti-D concentrations in maternal serum, fetal serum and amniotic fluid, and the development of fetal anaemia. DESIGN: Observational cross sectional and longitudinal study. SETTING: Regional referral centre. SUBJECTS: Sixty-one women undergoing fetal blood sampling at 19 to 36 weeks' gestation for fetal blood and haematocrit estimation for the management of Rh (D) allo-immunisation. Thirty-eight pregnancies (7 with an Rh (D) negative fetus) were tested only once but the rest had two to five fetal blood samplings. INTERVENTIONS: Ultrasound guided fetal blood sampling and amniocentesis, and automated analysis of anti-D antibody quantitation. RESULTS: There were strong correlations between maternal serum, fetal serum and amniotic fluid anti-D concentrations. Analyses of both longitudinal and cross sectional data demonstrated a decrease of the maternal/fetal serum anti-D ratio with gestation. In pregnancies with Rh (D) negative fetuses the maternal/fetal anti-D ratio was significantly lower (P < 0.0001) than in those with Rh (D) positive fetuses. The degree of fetal anaemia (delta haematocrit) was correlated with maternal serum and amniotic fluid anti-D concentrations (r = -0.55, n = 54, P < 0.0001; r = -0.57, n = 44, P < 0.0001, respectively) but there was a weaker correlation with fetal serum anti-D (r = 0.37, n = 54, P < 0.01). CONCLUSION: Anti-D concentrations in maternal serum, fetal serum and amniotic fluid are correlated with fetal anaemia. The decrease in maternal/fetal anti-D ratio with gestation suggests an increase in placental permeability for anti-D with advancing pregnancy.

Amniotic Fluid↗

Oxytocin-stimulated phosphoinositide hydrolysis in human myometrial cells: involvement of pertussis toxin-sensitive and -insensitive G-proteins.

Phosphoinositide hydrolysis is important in mediating the actions of oxytocin and prostaglandin (PG) F2 alpha on uterine contractions during labour. We have measured the effect of oxytocin, PGF2 alpha and other agents on the formation of inositol phosphates (IPs) in cultured human myometrial cells labelled with [3H]inositol and on changes in intracellular free Ca2+ concentration ([Ca2+]i) in cells loaded with Fura-2. Oxytocin induced the formation of [3H]IPs in a concentration-dependent manner with an EC50 (concentration of agonist producing 50% of the maximal response) of 1.4 +/- 0.5 nmol/l (mean +/- S.E.M.). The maximal response was obtained with 1 mumol oxytocin/l and represented a stimulation of 670% over basal. PGF2 alpha also stimulated the formation of [3H]IPs and the response at 1 mumol/l was a 204% stimulation over basal. The effects of PGF2 alpha were independent of extracellular Ca2+ but the effect of oxytocin was reduced with low extracellular Ca2+. Cyclic AMP formation, induced by forskolin or PGE2, had no effect on the stimulated levels of [3H]IPs. Pertussis toxin (PT) reduced the oxytocin-stimulated formation of [3H]IPs in a concentration-dependent manner. The maximal effect of PT resulted in an 80% reduction in the formation of [3H]IPs. However, PGF2 alpha stimulation was not affected by PT treatment. To analyse the action of PT further, we studied its effect on oxytocin-induced changes in [Ca2+]i. The basal [Ca2+]i was 112 +/- 4 nmol/l (n = 225 cells) and was not affected by PT treatment (109 +/- 3 nmol/l; n = 200 cells). In the absence of PT, 1 mumol oxytocin/l increased [Ca2+]i to a peak of 522 +/- 26 nmol/l, and in PT-treated cells, the [Ca2+]i peak was reduced to 348 +/- 16 nmol/l. Similar inhibitory effects of PT were obtained at oxytocin concentrations ranging from 1 to 100 nmol/l. Our data suggest that in human myometrial cells, the oxytocin-induced production of [3H]IPs and increase in [Ca2+]i are mediated by a PT-sensitive G-protein. However, a significant fraction of the oxytocin response appears to be mediated by a PT-insensitive G-protein, possibly a member of the Gq family.

Calcium↗

The unripe cervix and its management for labour induction.

Cervical state plays an important part in the outcome of induced labour. The mechanism governing the process of ripening, which is part of the continuum ending in labour, is still not fully understood, but is thought to involve several hormonal interactions including oestrogens, progesterone, and prostaglandins. The prostaglandins have been found to produce the best results for inducing labour when the cervix is unripe and are most effective when administered locally and most convenient when placed in the vagina as a viscous gel, wax pessary or slow release pessary. They are of benefit for labour induction in cases previously delivered by lower segment caesarean section, breech presentation, and multiple pregnancies. Hyperstimulation and fetal distress may occur and this might be reduced with the use of the controlled release hydrogel pessary. Newer approaches using an antiprogestin or recombinant relaxin are being explored in the hope that further improvements in outcome can be obtained.

Administration, Intravaginal↗

Does amniotic fluid analysis reflect acid-base balance in fetal blood?

OBJECTIVE: The purpose of the study was to examine whether the acid-base balance in amniotic fluid reflects the acid-base state in fetal blood. STUDY DESIGN: The pH, PCO2, PO2, bicarbonate, and base excess concentrations were measured in umbilical venous, umbilical arterial, and maternal venous blood and in amniotic fluid samples obtained at fetoscopy. This was performed before intraamniotic termination of 16 normal pregnancies (mean gestation 19.4 weeks), as well as in 14 red blood cell isoimmunized pregnancies (mean gestation 28.4 weeks) undergoing fetoscopy for the diagnosis and treatment of fetal anemia. RESULTS: In normal pregnancies, amniotic fluid pH and bicarbonate were significantly lower than umbilical venous and umbilical arterial blood concentrations, and this was due to the high concentration of base deficit in amniotic fluid. Whereas amniotic fluid PCO2 did correlate significantly with fetal umbilical venous PCO2 values, there was no correlation between other acid-base characteristics. CONCLUSION: Simultaneous sampling of human fetal umbilical blood and amniotic fluid under the acute conditions of this study did not show significant correlations in acid-base values.

Acid-Base Equilibrium↗

Cellular schwannoma of the vagina.

Schwannomas of the female genital tract are rare, and an example in the vagina has not previously been reported. The case of a 37-year-old woman with a cellular schwannoma of the vagina is described and is accompanied by a review of schwannomas in the female genital tract.

Adult↗