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Biomedical subjects

W G McBride

Publications and source records attributed to W G McBride.

At least 19 recordsLinked to original sources
PubMed1990

Thalidomide induced alteration in secondary structure of rat embryonic DNA in vivo.

Teratogenicity of thalidomide was demonstrated in Wistar rats following a single maternal intravenous injection during the embryonic organogenetic period. When compared to day 13 embryonic DNA isolated from untreated control mothers, differences were observed in the mean wet weights of day 13 embryos from rats treated with thalidomide during days 10 or 11 of gestation, and significantly less amounts of embryonic DNA were recovered from mothers similarly treated on days 10 or 12 of their respective gestation periods. Rat embryonic DNA may be separated into two fractions by stepwise elution from benzoylated DEAE-cellulose (BD-cellulose) columns with 1.0 M NaCl (SE-DNA) and 1.8% (w/v) caffeine (CE-DNA) solutions, respectively. Other studies using bacterial, yeast, and rat liver DNA suggested that the first fraction contains native DNA, whereas the second may exhibit some degree of single-stranded character. Similar reproducible chromatographic profiles were obtained using a novel "batch method" developed for general application. Rat embryonic DNA was monitored by labelling in vivo with an i.p. injection of [methyl-3H]-thymidine (3H-TdR) during days 5, 6, and 7 of the gestation period. All samples were analysed on day 13 of gestation. A simple increase in percentage of caffeine-eluted DNA was not detected in thalidomide treated samples; however, diversity of percent (%) CE-DNA within litter was noted. Briefly, the percent CE-DNA values for embryos in one litter were ranked and arbitrarily grouped in classes with limits of mean +/- 1 SD, mean +/- 2 SD, and so on to generate a characteristic profile of percent CE-DNA distribution. The number of embryos within the range of each SD unit was expressed as a percentage of each litter. A plot of the ranges of percent CE-DNA versus percentage of each litter was used to illustrate the distribution profile of the particular litter and to be used for comparison between samples from untreated control and thalidomide and/or dimethylformamide (DMF) treated DNA. Treatment of day 12 mothers with thalidomide produced a majority of embryos having percent CE-DNA values similar to those of untreated controls with the exception of the inclusion of a second population of embryos with much higher percent CE-DNA values than those of the untreated controls. Similar treatment of day 11 animals produced a majority of embryos still having percent CE-DNA values similar to those of untreated controls and also having a second group of embryos with a lower percent CE-DNA values than those of untreated controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Teratological study of malathion in the rabbit.

There has been much debate concerning the teratogenic potential of the organophosphate pesticides, including malathion, although few experimental studies have been performed on mammals. This study was designed to expand the range of animal species used in the testing of malathion and to further evaluate malathion's teratogenic potential. A 100-mg/kg dose regimen from d 7 to d 12 of gestation was administered to New Zealand white rabbits. This produced no detectable differences in the number of resorptions, fetal size, and external or visceral anomalies between the treated and control groups. This suggests, as has been previously reported, that malathion has little or no teratogenic potential in the mammal.

Abnormalities, Drug-Induced↗
PubMed1987

Acetylcholine and choline levels in rabbit fetuses exposed to anticholinergics.

It has been hypothesized that acetylcholine, choline acetylase and acetylcholinesterase may have an ontogenic and trophic influence in the embryo, and that therefore certain drugs may produce malformations via their effect on the acetylcholine and choline levels in the fetus. Thalidomide and the anticholinergics, scopolamine hydrobromide and orphenadrine hydrochloride, and doxylamine succinate, an antihistamine with secondary anticholinergic action, were administered to pregnant New Zealand White rabbit does from day 8 to day 15 of gestation. Cesarean sections were performed on gestational day 16, the fetuses removed and the acetylcholine and choline contents of the fetuses and placentas were estimated by organic extraction and derivation for injection into a GCMS. These acetylcholine and choline levels were compared with those of the fetuses and placentas of the control animals mated with the same buck on the same day as the treated animals. Thalidomide (50 mg/kg) did not affect acetylcholine or choline levels in the fetuses or the placentas obtained from the treated animal. Scopolamine (approximately 100 micrograms/kg) reduced the choline level in the placenta and fetus but not the acetylcholine levels. Orphenadrine (approximately 24 mg/kg) reduced acetylcholine and choline levels in the fetus and choline levels in the placenta. Doxylamine succinate (10 mg/kg) reduced the acetylcholine levels in the fetus and the choline levels in the placenta. The placenta is a fetal organ and the significance of acetylcholine production by the placenta is as yet unknown. The reduction in acetylcholine levels in the fetus exposed to drugs with an anticholinergic action may be of significance in the production of malformations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1979

Children born after elective induction of labour.

A comparison was made between the performance at eight years of age of 63 children who were born after elective induction of labour, and 29 spontaneously born children. The children had been tested previously at five years of age. Tests of reading and arithmetic achievement, visuomotor coordination, aural-visual coordination, auditory discrimination, and behavioural rating scales were administered. On two of the 12 measures (reading comprehension and euroticism) the induced children performed better than the spontaneously born. On all other measures there were no significant differences. There appeared to be no evidence of specific learning disabilities or behavioural problems among the induced children.

Achievement↗
PubMed1979

Method of delivery and developmental outcome at five years of age.

A controlled follow-up study examined the impact of delivery method on developmental outcome of the child. The modes of delivery investigated were low forceps delivery (188 infants), midcavity forceps delivery (51 infants), forceps rotation with forceps delivery (57 infants), manual rotation with forceps delivery (67 infants), elective caesarean section (101 infants) and spontaneous delivery (control, 207 infants). Breech presentation (100 infants) was separately compared with the vertex presentation groups. Sample selection controlled for complications during pregnancy and low birthweight and was restricted to married English-speaking mothers. The children were assessed at the age of five years on verbal and non-verbal subtests of a standardized intelligence scale, tests of gross motor coordination, and auditory and visual tests. A full paediatric examination was also performed. Breech presentation children performed less well on tests of balance and fine motor coordination and on visual acuity and stereopsis testing than children who presented in the vertex position. No deleterious effect of delivery method was found. In the absence of other complicating events (like a poor antenatal history, prematurity, and a disorganized home environment) delivery complication constitutes an early risk factor which the growing child is able to overcome.

Cesarean Section↗
PubMed1979

Disposition of synethetic glucocorticoids. I. Pharmacokinetics of dexamethasone in healthy adults.

The pharmacokinetics of dexamethasone alcohol is described in six male and six female healthy adult volunteers who each received 8 mg of dexamethasone phosphate by bolus intravenous injection. Quantitation of the alcohol was done using a high-performance liquid chromatographic method with improved specificity. Statistical evaluation of the results generated by nonlinear least-squares regression analysis of the plasma concentration-time data shows that the phosphate ester is very rapidly hydrolyzed to the alcohol and a biexponential equation is the simplest polyexponential equation that is consistent with the data. The terminal phase half-life t1/2 beta was significantly greater (P less than 0.05) in males (mean 201.5 min) than in females (mean 142.3 min). They prolonged t1/2 beta in males did not appear to be caused by an impaired capacity to eliminate dexamethasone since the total plasma clearance did not differ between males (mean 24.5 ml/min) and females (mean 242.9 ml/min). There was, however, a high positive correlation between t1/2 beta and Vdss among the 12 adults (r = 0.92, p less than 0.001). There were also significant correlation between Vdss and body weight (r = 0.67, p less than 0.05) and t1/2 beta and body weight (r = 0.80, p less than 0.01). The difference in body weight between the sexes seems to be the main factor contributing to the difference observed in t1/2 beta. An average of only 2.6% of the dose was found unchanged in a 24-hr urine sample, and hence it appears that dexamethasone is primarily eliminated by extrarenal, probably hepatic, mechanisms.

Adult↗
PubMed1978

Quantitation of dexamethasone in biological fluids using high-performance liquid chromatography.

A sensitive and specific method for the quantitation of dexamethasone in plasma and urine is described. The specificity of the method is obtained using adsoprtion chromatography on a high-performance liquid chromatograph. The dexamethasone is detected with a variable-wavelength UV detector. An internal standard technique is used for quantitation of dexamethasone with a minimum sensitivity of 15 ng. Preliminary results of the application of the method to pharmacokinetic studies of dexamethasone in humans are reported.

Chromatography, High Pressure Liquid↗
PubMed1977

A study of five year old children born after elective induction of labour.

A controlled retrospective study of some short-term and long-term effects of elective induction of labour was conducted. There did not appear to be any increase in the incidence of maternal complications during labour, or of neonatal problems in the induced-labour group compared with the remainder of the mothers in the hospital. In the follow-up phase of the study, two treatment groups of children who were delivered after amniotomy and amniotomy plus the administration of oxytocin were compared with each other, and with a control group of children born after spontaneous labour. The children were assessed at the age of five years on verbal and non-verbal subtests of a standardized intelligence scale, tests of gross motor and fine motor coordination, and auditory and visual tests. A full physical examination was also performed. No statistically significant differences nor trends of clinical interest were found between the groups on any measure.

Birth Weight↗
PubMed1976

Ultrastructural changes in the dorsal root ganglia evoked by thalidomide in rabbits.

Administration of the teratogenic drug thalidomide to pregnant does produces ultrastructural changes in foetal ganglion cells, Schwann cells and axons in the posterior root ganglia corresponding to forelimb segments deformed by the orug. Ultrastructural changes in ganglia appear on the 13th day of gestation, i.e., preceding the appearance of limb malformation.

Animals↗