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Biomedical subjects

G V Chamberlain

Publications and source records attributed to G V Chamberlain.

At least 19 recordsLinked to original sources

Lactic acidosis. A presentation of metastatic breast cancer arising in pregnancy.

Lactic acidosis B is a rare metabolic complication of malignancy. It usually is associated with advanced and extensive metastatic disease. The authors report a case in which lactic acidosis was the presenting feature of a previously undiagnosed case of metastatic breast cancer in a pregnant woman and that resolved with successful antineoplastic treatment. The authors review the likely cause and management of the condition.

Acidosis, Lactic

Early Doppler ultrasound screening in prediction of hypertensive disorders of pregnancy.

1198 nulliparous women were screened in early pregnancy (median 18 weeks' gestation) by the recording of doppler ultrasound waveforms from the uteroplacental circulation. After exclusions, the results of 1014 women were available for analysis; 118 (12%) of them had persistently abnormal waveforms on repeat ultrasound scans at 24 weeks and were taken to have a positive test result. Hypertension was significantly more frequent among those women than among women with normal doppler waveforms (29/118 [25%] vs 45/896 [5%]). In addition, hypertension in women with abnormal waveforms was more likely to be severe; 12 (10%) had proteinuria and 15 (13%) intrauterine growth retardation compared with 7 (0.8%) and 0, respectively, of those with normal waveforms. Overall, the test did poorly when assessed by standard statistical means. However, the sensitivity was high for hypertension associated with either proteinuria (63%) or intrauterine growth retardation (100%). The test is cheap, easy to carry out, and non-invasive, and it can be done in early pregnancy; it is therefore a useful means of identifying a high-risk group of pregnant women suitable for therapeutic intervention to reduce the incidence of hypertensive disorders and their complications.

Adult

Doppler ultrasound and aspirin in recognition and prevention of pregnancy-induced hypertension.

Screening of 1226 nulliparous women by means of doppler uteroplacental flow-velocity waveforms in early pregnancy identified 148 (12%) as being at high risk of pregnancy-induced hypertension. After exclusions and refusals, 100 women were randomly allocated to groups receiving either low-dose aspirin (75 mg daily; 48 patients) or identical placebo (52 patients) for the remainder of the pregnancy. The difference between the aspirin and placebo groups in the frequency of pregnancy-induced hypertension (13% vs 25%) did not achieve significance, but there were significant differences in the frequencies of proteinuric hypertension (2% vs 19%) and hypertension occurring before 37 weeks' gestation (0% vs 17%). Fewer aspirin-treated than placebo-treated women had low birthweight babies (15% vs 25%), but this difference was not significant. The only perinatal death in the aspirin group followed a cord accident during labour, whereas the 3 perinatal deaths in the placebo group were all due to severe hypertensive disease. No maternal or neonatal side-effects were observed in either group.

Administration, Oral

Mechanisms of parturition: the transfer of prostaglandin E2 and 5-hydroxyeicosatetraenoic acid across fetal membranes.

Prostaglandin E2 production by amnion is thought to be an important event in the onset of human labor. It has been suggested that 5-hydroxyeicosatetraenoic acid, also produced in the amnion, may mediate prelabor contractions. For either of these compounds to play a paracrine role they need to cross the chorion, which has a high capacity to metabolize prostaglandins. With the use of an in vitro system we have shown that both prostaglandin E2 and 5-hydroxyeicosatetraenoic acid cross either amnion or intact amnion-chorion-decidua at a rate similar to that of an extracellular marker sucrose. Analysis by high performance liquid chromatography revealed that at physiologic concentrations neither prostaglandin E2 nor 5-hydroxyeicosatetraenoic acid were metabolized by amnion alone. Moreover, 100% of the 5-hydroxyeicosatetraenoic acid and 72% of the prostaglandin E2 remained in the active form after passage across intact amnion-chorion-decidua. There did not appear to be any difference in the rate of transfer or permeability of the membranes before or after spontaneous labor. We conclude that both 5-hydroxyeicosatetraenoic acid and prostaglandin E2 synthesised in the amnion can cross the membranes by diffusion through the extracellular space, remaining largely unmetabolized, and may play a role in the onset of human labor.

Biological Transport

Flecainide excretion in human breast milk.

Healthy human volunteers who intended not to breast feed were placed on a regimen of 100 mg oral flecainide every 12 hours for 5 1/2 days beginning 1 day after parturition. Milk and blood samples were collected during the dosing period and for 2 days after the last dose. Concentrations of flecainide in milk and plasma were assayed by HPLC. Apparent steady-state levels of flecainide in both milk and plasma were achieved in most cases by day 4 of the study. Highest daily average concentration of flecainide in milk ranged from 270 to 1529 ng/ml for the 11 subjects. Mean +/- SD milk to plasma flecainide ratios were 3.7 +/- 3.5, 3.2 +/- 2.3, 3.5 +/- 2.1, and 2.6 +/- 0.7 on study days 2, 3, 4, and 5, respectively. After the last dose of flecainide, peak milk levels of the drug occurred at 3 to 6 hours and then declined monoexponentially. The half-life for elimination of flecainide from milk was 14.7 +/- 3.5 hours and is very similar to the plasma elimination half-life of flecainide in healthy human subjects. The mean milk to plasma ratios for flecainide after the last dose were 2.3 +/- 1.0 and 2.9 +/- 1.1 at 24 and 48 hours after the dose, respectively. Based on the pharmacokinetics of flecainide in infants, the expected average steady-state plasma concentration of flecainide in a newborn infant consuming all of the milk production of its mother (approximately 700 ml/day) would not be expected to exceed about 62 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Non-steroidal follicular factors attenuate the self-priming action of gonadotropin-releasing hormone on the pituitary gonadotroph.

Pituitary glands of pro-oestrous and oestrous rats were perifused in series with isolated ovarian follicles and the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses to gonadotropin-releasing hormone (GnRH) were measured. Pituitary glands from pro-oestrous rats, perifused with the effluent medium from isolated preovulatory follicles, showed a significant reduction in the self-priming effect of GnRH as observed from the typical biphasic LH response to a continuous GnRH challenge. The initial FSH response to GnRH was also reduced. A similar trend was seen in the LH responses of pituitary glands from oestrous rats but results were not significant; there was no parallel reduction in FSH release. It is unlikely that the attenuation of GnRH self-priming was due to the steroids released by the isolated follicles. LH responses of pro-oestrous pituitaries, perifused with medium containing 200 pg oestradiol/ml, 5 ng progesterone/ml or 200 pg testosterone/ml were similar to paired controls as were the responses when all three steroids were added to the perifusing media at identical concentrations. Furthermore, when steroids were charcoal extracted from the effluent medium of perifused isolated follicles the biological activity of this medium in attenuating GnRH self-priming was not destroyed. Finally, the effects of purified bovine inhibin and steroid-free human follicular fluid (hFF) on LH responses were compared. Purified inhibin at a concentration of 20 or 50 ng/ml perifusing medium had no effect on GnRH-stimulated LH release although GnRH-stimulated FSH secretion was significantly reduced toward the end of an extended perifusing period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ultrasound evaluation of amniotic fluid: outcome of pregnancies with severe oligohydramnios.

We studied a group of 247 patients out of 7725 patients who had an ultrasonic examination between 32 and 36 weeks gestation and were found to have oligohydramnios (amniotic fluid volume (AFV) less than or equal to 2.0 cm). We compared the features of labor and mode of delivery and perinatal outcome in this group with that of a normal control group of 247 patients who also had an ultrasonic examination between 32 and 36 weeks gestation and were found to have normal AFV (greater than 2.0 to less than 8.0 cm). The incidence of induction of labor, of elective cesarean section, of preterm delivery (less than 37 weeks' gestation) was significantly higher in the oligohydramnios group (study group) as compared with the incidence in the control group (P less than 0.05). The incidence of fetal distress in antenatal and intrapartum period, pH (less than or equal to 7.2), of low Apgar score (0-5), of intrauterine growth retardation (IUGR) (less than tenth centile) infants, of major fetal anomaly and perinatal mortality rate (PNMR) are significantly higher in the oligohydramnios group as compared with the incidence and PNMR in the normal control group (P less than 0.05). The ultrasonic finding of oligohydramnios should alert the clinician regarding the possibility of problems in labor and perinatal period.

Adult

The relationship of increased amniotic fluid volume to perinatal outcome.

We studied a group of 135 patients with polyhydramnios diagnosed on the basis of ultrasonic findings (greatest vertical diameter of the liquor column greater than or equal to 8.0 cm) between 32 and 36 weeks gestation (study group). We compared the obstetric characteristics and perinatal outcome of the study group with a similar number who constituted our control group. The incidence of women aged 20 years or less was higher in the study group (8.9%) compared with 4.5% in the control group. Of the 135 patients who were diagnosed to have polyhydramnios ultrasonically, the clinical diagnoses prior to referral for ultrasonic scanning, were, suspected large for date fetuses in 34 patients (25.2%), clinically suspected polyhydramnios in 28 (20.7%), gestational diabetes in 21 (15.6%) and insulin dependent diabetes in 6 (4.4%) compared with 13.3%, 5.2%, 3.0% and 0.7%, respectively in the control group (P less than 0.05). Preterm delivery occurred in 11.1% in the study group compared with the incidence of 6.7% in the control group. The incidence of fetal distress, low Apgar Score, macrosomic infants, major fetal anomalies, gross and corrected perinatal mortality rate and admission to special/intensive care nursery was significantly higher in the study group compared with that of the control (P less than 0.01). We found ultrasonic examination is a reliable technique to assess the amount of amniotic fluid volume and it alerts the clinician to possible future problems in pregnancy, labor and neonatal period.

Adult

Ultrasonically guided percutaneous umbilical blood sampling in the management of intrauterine growth retardation.

Ten patients, hospitalized because of severe asymmetrical fetal growth retardation before 32 weeks gestation, underwent ultrasonically guided percutaneous umbilical blood sampling because of concern over the fetal heart rate trace. In eight patients the fetus was judged to be acidotic and they were delivered immediately by caesarean section. In two patients the fetus was not considered to be acidotic and the pregnancy was allowed to go on. In those babies that were delivered the pH blood collected from the umbilical vein at the time of delivery was compared to the antenatal sample. There were no significant differences. The technique of antenatal umbilical vein blood sampling is readily learned and by assessment of fetal acid base status a more precise diagnosis can be made leading to appropriately planned management.

Acidosis

The use of a birthroom: a randomized controlled trial comparing delivery with that in the labour ward.

A randomized controlled trial of two environments for delivery was conducted at Queen Charlotte's Maternity Hospital. A total of 253 parous women expecting to have a labour ward delivery were invited to participate in the trial but only 148 agreed. These women were randomly allocated to be delivered either with standard labour ward management (n = 72) or in the birthroom--a small bedroom decorated in a homely manner, without facilities for epidural analgesia or electronic fetal monitoring (n = 76). Eleven women in the birthroom group and 10 in the labour ward group withdrew from the trial before labour and four were transferred from the birthroom to the labour ward when in labour. A questionnaire sent in the postnatal period to the women who completed the trial was returned by 80%. In the birthroom group there was significantly (i) decreased admission-to-delivery interval (ii) less analgesia (iii) more freedom of movement (iv) less suturing (v) increased rooming-in. No difference was found in the assessment of difficulty of labour nor in the method of subsequent infant feeding.

Clinical Trials as Topic

Factors associated with delayed onset of regular respiration.

In a population of 16333 singleton births born in one week of April, 1970, 4.4% failed to establish regular respiration within 3 min of birth. A follow-up at 5 years of age collected medical, educational and sociological information on 79.6% of the survivors of the cohort identified by the birth survey. Data have been analysed to investigate the relationships between the delay in the onset of regular respiration and possible risk factors identifiable prior to or at the time of birth. Complex statistical analysis employing linear modelling techniques showed that the delay in the onset of respiration was primarily related to: null and high parity; antepartum haemorrhage (especially placenta praevia); pre-eclampsia; breech delivery; Caesarian section and low birthweight. There was no association with maternal smoking during pregnancy or with social class. These conclusions are reasonably consistent with those drawn from other studies using alternative measures of asphyxia.

Child, Preschool

Delayed onset of regular respiration and subsequent development.

A comprehensive survey carried out at birth, data on mortality and a 5 year follow-up covering medical, educational and sociological aspects of child development were available for singleton births born in one week of April 1970. The survey at 5 years of age included 12363 children, 79.6% of the surviving cohort. An assessment has been made of the extent to which delay in the onset of regular respiration at birth is associated with the subsequent development of the child. Using the results of our previous investigations, the relationships between this delay and other factors known at the time of birth have been taken into account. The distributions of a large number of development variables were not significantly different for groups of children determined by respiratory delay at birth, but there was an association with mortality and cerebral palsy. In addition, there was an unexpected relationship between delayed onset of respiration and subsequent bronchitis. This association remained significant after controlling for possible confounding effects using linear modelling techniques.

Bronchitis

Trial of the use of masks in the gynaecological operating theatre.

A randomly controlled trial was performed on 41 women having gynaecological surgery in which the team of surgeons and nurses wore or did not wear masks. After major abdominal surgery, 3 of 5 patients in the unmasked group developed wound infections whereas no infection was observed in the 4 patients of the masked group. A greater number of Streptococci were also found by settle-plates on the operating table in the unmasked group. No infection was recorded after minor or vaginal surgery.

Abdomen

Plus ça change: predictors of birthweight in two national studies.

The 16 989 singleton births in one week of March, 1958, studied by the British Perinatal Mortality Survey, were subjected to an analysis of covariance, which showed that major factors associated with birthweight of the infant were: maternal height, history of smoking in pregnancy, parity and history of pre-eclampsia during the pregnancy. The same analysis was repeated on the data collected on 16792 singletons born 12 years later in one week of April, 1970 and studied by the British Births Survey. In spite of major changes in obstetric practice and in the maternal population, the same factors were shown to be highly significant and the magnitude of the associations had changed little.

Analysis of Variance

Some problems of alpha-fetoprotein screening.

In two years of a routine screening programme for the detection of neural-tube defects over 6000 women had serum-alpha-fetoprotein (A.F.P.) measured. As a result, 80 women carrying live singleton fetuses were offered amniocentesis under ultrasound control. All neural-tube defects detected at birth were recorded and necropsies were done routinely on abortuses, thus permitting evaluation of the screening programme in terms of false negatives and false positives. 16 amniotic-fluid A.F.P.s were abnormal, 1 for an unaffected fetus; and 2 others were normal for fetuses which had closed lesions. At the serum-A.F.P. stage, 3 lesions were missed. The detection-rate compares favourably with those of other series. However, in a pilot study, routine ultrasonic assessment of gestation yielded a substantial proportion of cases where a serum-A.F.P. deemed normal or abnormal when gestation was assessed clinically would have been misleading. Loss of normal fetuses subsequent to amniocentesis (5 in this series) also has to be taken into account.

Abortion, Therapeutic

How obstetricians manage hypertension in pregnancy.

One thousand and ninety-three obstetricians answered a questionnaire on the management of pregnant women with pre-existing hypertension and pre-eclampsia. They reported that they frequently used antihypertensive drugs (most often methyldopa and diuretics) in severe essential hypertension but tended to give sedatives in mild cases. Renal impairment was considered more important that raised blood pressure as an indication for terminating pregnancy; but even without a raised blood urea concentration over a quarter of respondents (especially the more senior obstetricians) would have considered it. The more junior obstetricians were more likely to admit the least severely affected patients to hospital. Pre-eclampsia was usually treated with bed rest and sedatives (most frequently diazepam); but the choice of drug varied with the seniority of the respondents, the more senior obstetricians tending to confine themselves to the more familial drugs. There was considerable unanimity in the replies, even though most of the treatments and practices have not been validated by controlled trials, and two-thirds of the obstetricians gave the same answers to most of the questions.

Abortion, Therapeutic