Search PubMed⌕ Search

Biomedical subjects

D A Edwards

Publications and source records attributed to D A Edwards.

At least 73 records · Page 4Linked to original sources
PubMed1988

Vitamin E, membrane order, and antioxidant behavior in lung microsomes and reconstituted lipid vesicles.

Vitamin E, a dietary antioxidant, is known to inhibit peroxidation of membrane lipids and to protect the lungs of vitamin E-deficient animals and to a lesser extent vitamin E-sufficient animals from oxidant injury. Since the protective interaction between vitamin E and biological membranes may be related to alterations in composition and physical state of membrane lipids, we evaluated the effect of vitamin E deficiency on lung microsomal lipids and membrane fluidity. Both intact microsomes and lipid vesicles prepared from the total lipid extracts of these microsomes were used. The percentage incorporation of vitamin E and cholesterol, membrane fluidity, and lipid peroxidation were measured in microsomes as well as their lipid vesicles. Fluidity was measured by monitoring changes in fluorescence anisotropy for 1,6-diphenyl-1,3,5-hexatriene (DPH). Lipid peroxidation was measured by thiobarbituric acid reaction. There were significant increases in the phospholipid (p less than 0.01), the total cholesterol (p less than 0.05), and the total saturated fatty acids (p less than 0.05) and decreases in total polyunsaturated fatty acid (p less than 0.01) content of vitamin E-deficient microsomes. There were no detectable peroxidative products in freshly isolated microsomes from either vitamin E-sufficient or -deficient lungs. However, lipids from vitamin E-deficient microsomal membranes were more susceptible to free radical initiated peroxidation than lipids from vitamin E-sufficient microsomes. Fluidity in vitamin E-deficient microsomes or in their lipid vesicles was significantly (p less than 0.05) decreased compared to the respective controls. In vitamin E-deficient microsomes or their lipid vesicles, the incorporation rate of vitamin E was two- to three-fold greater than in vesicles of vitamin E-sufficient microsomes or their lipid vesicles. However, the percentage incorporation of cholesterol was identical in both vitamin E-deficient and vitamin E-sufficient microsomes or in their respective lipid vesicles. As a result of vitamin E incorporation, fluidity was significantly decreased (p less than 0.05) in vitamin E-sufficient vesicles and was further decreased (p less than 0.001) in vitamin E-deficient vesicles. Incorporation of cholesterol also decreased fluidity in both vitamin E-deficient and vitamin E-sufficient vesicles but to the same extent (p less than 0.001). Lipid peroxide formation was two-fold greater in the vitamin E-deficient than in the vitamin E-sufficient vesicles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

[Subthalamic lesions eliminate sexual behavior in the male rat].

Electrical stimulation of parts of the subthalamus and mesencephalon produces coordinated stepping movements, and for this reason these areas are sometimes referred to as the subthalamic and mesencephalic "locomotor" regions. In this study we contrast the sexual behavioral effect of electrolytic destruction of these two regions in the male rat. Lesions of the mesencephalic locomotor region had no significant effect on male sexual behavior. In contrast, subthalamic lesions centered on the caudal zona incerta just dorsal to the subthalamic nucleus eliminated sexual behavior in 6 of 15 males. The sexual behavior of the remaining males was affected to a lesser degree, for the most part in accord with the extent of destruction to this "critical zone." Subthalamic lesions produced no obvious impairment in locomotion, posture, limb use, muscle tone or sensorimotor orientation. Even so, the fact that electrical stimulation of the subthalamus elicits coordinated stepping suggests that the region is linked with systems directly concerned with movement and locomotion. These links could be particularly important in the process by which sexual motivation is translated into sexual behavior.

Animals↗
PubMed1987

Evidence for an olfactory receptor which responds to nicotine--nicotine as an odorant.

The tobacco alkaloid (S)(-)-nicotine, when applied as a vapour to an in vitro head preparation, stimulates the olfactory epithelium in three strains of rats and to a lesser extent in two strains of mice. The electro-olfactogram (EOG) generated by nicotine has similar characteristics to the EOGs produced by known odorants. The nicotine EOG increases with increasing concentration of nicotine vapour (1-100 nM) applied to the olfactory epithelium. Differential reduction of the nicotine EOG by the lectin concanavalin A is seen in Wistar and Lister Hooded rats. The reduction of the nicotine EOG by concanavalin A is prevented by adding alpha-methyl-D-mannoside to the lectin superfusion medium. This suggests that there is a glyco-moiety associated with at least one olfactory receptor responding to nicotine. Our results suggest that rat olfactory epithelium has receptor sites for nicotine. Nicotine is an unusual compound because it shows both odorant and pharmacological properties.

Animals↗
PubMed1987

The effect of concanavalin A on the rat electro-olfactogram at various odorant concentrations.

We have studied the effect of concanavalin A (Con A) on the rat electro-olfactogram response to several odorants. Each odorant was applied over a range of concentrations. For hydrophobic odorants whose response was affected by Con A, the diminution in response was maximal at odorant concentrations of about 1 microM in the olfactory mucus. The (odour) concentration-dependence of the change is compatible with the idea that Con A inactivates one or more types of olfactory receptor that normally bind odorants with dissociation constants of the order of 100 nM. With hydrophilic odorants we had to apply concentrations very much higher than this to elicit any response from the system. At these high concentrations we could observe Con A-induced diminutions in response.

Animals↗
PubMed1987

Testicular hormones during the first few hours after birth augment the tendency of adult male rats to mount receptive females.

In the male rat, a dramatic increase in serum testosterone of testicular origin occurs during the first two hours of postnatal life. This experiment was designed to determine whether this increase contributes to the development of the propensity for adult male rats to mount sexually receptive females. Male rats were castrated at either 0-hours (virtually at the moment of birth), or at 6 hours, or at 24 hours after birth. Some males castrated at 0-hours were injected with 1 microgram of testosterone after surgery. Control males were sham-operated at birth, and castrated in adulthood. At about 90 days of age, each male was given testosterone replacement therapy and tested over a period of 6 weeks for mounting. Castration of newborn males retards the development of mounting in the sense that males castrated at 0-hours require a longer period of hormone stimulation before beginning to mount, a greater percentage of males castrated at 0-hours fail to mount altogether, and even those who do mount do so at a frequency significantly lower than that for males castrated later in life. These effects are not seen when males are given an injection of testosterone immediately after castration at 0-hours, or when castration occurs at 6 hours after birth or later. We conclude that gonadal hormonal stimulation during the first several hours after birth contributes to, although is perhaps not essential for, the development of mounting.

Animals↗
PubMed1987

Effect of progesterone on the testosterone and estradiol levels in the hypothalamus of neonatal rats.

Pregnant female rats were injected with progesterone or oil from 18.5 up to 21.5 days of gestation. Rat pups were delivered by caesarean section, and pups delivered from progesterone-treated mothers were injected with 100 micrograms of progesterone and pups from oil-treated mothers were injected with oil. Two hours after delivery, pups were killed and hypothalamic testosterone and estradiol were determined by RIA. Control males had substantially higher concentrations of testosterone and estradiol in hypothalamus than control females. Treatment with progesterone did not affect the accumulation of testosterone in the hypothalamic tissue of neonatal males, but completely prevented the formation of estradiol in hypothalamic tissue. This result suggests that progesterone can inhibit hypothalamic aromatase activity in the neonate and may explain why progesterone can protect against some of the neural defeminizing effects of neonatally administered androgens.

Animals↗
PubMed1987

Influence of the environmental temperature on the post-partum testosterone surge in the rat.

In the neonatal male rat, a rapid and transient increase in serum testosterone occurs about 2 h after birth. This post-partum testosterone surge (PPTS) has been implicated in the masculinization and defeminization of the central nervous system. The present study shows that environmental temperature can have a profound influence on the PPTS. Male rats were delivered from their mothers by caesarean section on day 22 of gestation. Immediately thereafter, neonatal males were placed at an ambient temperature of either 18, 21, 24 or 30 degrees C. With 2 h of exposure, the body temperature was in close correspondence with the ambient temperature. The PPTS was clearly abolished in the pups exposed for 2 h at either 18 or 21 degrees C. The effect of temperature was reversible: by placing pups at either 18 or 21 degrees C for 2 h after delivery, and then rewarming by placing them with a foster mother, the PPTS was delayed until 4 h after birth, i.e. 2 h after the beginning of rewarming. Thus, environmental cooling appears to retard the development of neural and/or endocrine systems mediating the PPTS. Aberrant maternal care which would produce substantial cooling of the male pups would be expected to affect the PPTS, which in turn might affect the sexuality of male progeny.

Animals↗
PubMed1986

Preoptic lesions increase the display of lordosis by male rats.

Male rats do not normally show feminine patterns of sexual behavior even when injected with the ovarian hormones estrogen and progesterone. We find that brain lesions which damage the preoptic-anterior hypothalamic continuum augment the display of lordosis in hormone-treated male rats. The most effectively feminizing brain lesions are ones which bilaterally destroy a substantial portion of the medial preoptic area encompassing the sexually dimorphic nucleus of the preoptic area (SDN-POA). Males with particularly large preoptic lesions are receptive following estrogen treatment and show a progesterone facilitation of receptivity. In this respect, they cannot be behaviorally distinguished from females. Thus, axons originating in and/or passing through the preoptic area apparently inhibit the display of feminine sexual behaviors in males. Preoptic development and lordosis are each predictably affected by perinatal stimulation by testicular hormones, and hormone-stimulated preoptic development may form the neurological basis for some of the defeminizing effects of perinatal hormonal exposure. Our results raise the possibility that the site of this behavioral defeminization is the SDN-POA.

Animals↗
PubMed1986

Preoptic and midbrain control of sexual motivation.

In a testing arena where a male rat can choose to spend time (and mate with) a sexually receptive female or choose a non-receptive female, a sexually motivated male will prefer the sexually receptive female and a decrease in preference for the receptive female can be said to reflect a decrease in sexual motivation. We have used a preference test to study the effects of castration and brain damage on sexual motivation. In neurologically intact males castration virtually eliminates copulation and decreases preference for a receptive female; copulation and preference are restored by replacement therapy with testosterone. Lesions of the medial preoptic area (MPOA) and lesions of the dorsolateral tegmentum (DLT) of the midbrain abolish copulation and decrease preference for a sexually receptive female. In lesioned males preference declines even further as testing is extended over a span of several months and is not affected by either castration or replacement therapy with testosterone. It seems likely that, at least in part, castration and brain damage decrease mating by decreasing sexual motivation. The MPOA and DLT are connected by axons running through the medial forebrain bundle, and we speculate that sex hormones may work on cells in the MPOA to increase sexual motivation and behavior, perhaps by altering the activity of axons projecting to the DLT which are principally involved in the mediation of sexual reward or "pleasure".

Animals↗
PubMed1986

Midbrain lesions, dopamine and male sexual behavior.

Destruction of the medial preoptic area (MPOA) eliminates mating in male rats and this region is believed to play a major role in the control of male sexual behavior. Efferents from the MPOA pass through and/or terminate in 4 midbrain regions: the dorsolateral tegmentum (DLT), the central gray, and the A9 and A10 areas. The present study reports the effects of bilateral destruction of each of these midbrain regions on brain catecholamines and sexual behavior in male rats. DLT lesions eliminated mating, reproducing the effect of bilateral preoptic lesions. The sexual activity of males with central gray lesions was accelerated in the sense that the mounting rate for these males was significantly faster than for controls and lesioned males ejaculated more frequently and with shorter latencies than did controls. A9 lesions impaired mating--lesioned males mounted at a slower rate and ejaculated less frequently than controls. Males with A10 lesions took longer to re-initiate mating after an ejaculation than controls, but copulation per se (as reflected in mount rate, ejaculation frequency and latency to ejaculate) was not affected by A10 damage. Brain catecholamine levels were not affected by either DLT or central gray lesions. A9 lesions produced a significant depletion in neostriatal dopamine which was highly correlated with mount latency, mount rate, ejaculation latency and ejaculation frequency. A10 lesions produced a significant depletion of dopamine in the nucleus accumbens and cingulate cortex, but these effects were not significantly correlated with any measure of sexual behavior.

Animals↗
PubMed1986

Screening for auditory dysfunction in high risk neonates.

Brainstem auditory evoked responses were recorded in 117 pre-term and 71 full-term infants from the general population of infants born at a referral obstetric unit. The threshold intensity required to evoke a reliable BAER was determined at different post-menstrual ages (PMAs) and in many cases at follow-up clinics. The BAER thresholds for 12 infants born and tested at less than 31 wk PMA were all greater than or equal to 50 dBHL. Sixty-two low-gestational-age infants who were tested between 31 and 36 wk PMA had BAER thresholds between less than or equal to 30 dBHL and greater than or equal to 80 dBHL. The majority of pre-term and term infants tested at term equivalent age had BAER thresholds less than or equal to 30 dBHL. Longitudinal studies also indicated that BAER thresholds can decline rapidly during the pre-term period. Follow-up studies showed that those pre-term and term infants with BAER thresholds less than or equal to 30 dBHL had normal auditory thresholds as determined using conventional behavioural testing at 4 or more months of age. Of those infants with BAER thresholds greater than or equal to 40 dBHL at the time of discharge or at term equivalent age, 67% (n = 16) were confirmed later as having a moderate to profound hearing deficit. The remaining 8 infants in this group had had BAER thresholds at term of 40 or 50 dBHL and had normal BAER and behavioural thresholds at follow-up. The cross-sectional and longitudinal data indicate that the majority of low-gestational-age infants who are at risk of hearing deficit achieve BAER thresholds less than or equal to 30 dBHL by term equivalent age. We recommend that auditory screening of infants in this group is best performed at the time of discharge from hospital or at term equivalent age, whichever is the later. Those infants with thresholds greater than or equal to 40 dBHL at that time should be encouraged to attend follow-up testing and, if high thresholds persist, they should then be referred on for behavioural testing and assessment for habilitative support.

Audiometry, Evoked Response↗
PubMed1986

Prediction of acetaminophen level from clinical history of overdose using a pharmacokinetic model.

A retrospective study was undertaken to determine the accuracy of predicting acetaminophen levels using the pharmacokinetic equation for first-order absorption and elimination of a single oral ingestion, (Formula: see text) Forty-four acute adult acetaminophen overdoses were studied during a 22-month period. Eighty levels drawn from 0 to 16 hours after ingestion were evaluated. To standardize the data, only first levels drawn in patients without prior spontaneous or ipecac-induced vomiting were analyzed (n = 26). Of these 26 levels, eight (31%) were drawn from 0 to two hours after ingestion, eight (31%) from two to four hours, and ten (38%) from four to 16 hours, with correlations of 0.59, 0.85, and 0.98, respectively. To determine the accuracy of predicting four-hour levels, five patients with first levels drawn at four hours, prior to vomiting, were evaluated. Substituting appropriate constants, the condensed equation, Cp4h = (0.59) (mg/kg dose), was used to predict the four-hour level (r = 0.99). Preliminary data suggest the ability to accurately predict four-hour acetaminophen levels from ingestion history alone using pharmacokinetic equations.

Acetaminophen↗
PubMed1986

Incidence and mechanism of bradycardia during apnoea in preterm infants.

Bradycardia occurred during 363 of 1520 apnoeas of 10 seconds' duration recorded in 28 preterm infants. The incidence increased with increasing duration of apnoea (10% of 10-14 seconds, 34% of 15-20 seconds, and 75% of greater than 20 seconds, p less than 0.001). This was similar for each type of apnoea--central, mixed, and obstructive. During 133 apnoeas in five infants the time from the start of the apnoea to the onset in the fall in oxygen saturation (mean 6.9 seconds) was significantly related to the onset of the fall in heart rate (mean 9.3 seconds) (r = 0.67, p less than 0.001). Recovery in heart rate coincided with resumption of air flow rather than breathing efforts and preceded the recovery in oxygen saturation. These results suggest that bradycardia occurs during apnoea as a response to falling oxygen saturation, probably through a peripheral chemoreceptor reflex that is manifest when breathing efforts are absent or ineffective.

Bradycardia↗
PubMed1985

The early development of head control in preterm infants.

This study documents the longitudinal development of head control in 104 infants born at 25-33 weeks gestation. Protective side turning of the head was found to have a developmental sequence of reducing spinal extension. In the 93 infants with normal motor outcome, individual differences in the rate of development correlated with caudo-cephalic muscle development (P less than 0.001, r = 0.5) but not with the length of extra-uterine experience. As a group, the 11 infants with later motor handicap showed a persistence of the early form of movement at 35-39 weeks post-menstrual age, without a significant correlation with the ratio of upper-lower limb muscle development. Head control, supine to sitting, in the infants with normal motor outcome showed variations in the rate of preterm development. The infants born at less than 31 weeks showed significantly higher scores at 33-35 weeks post-menstrual age than those born at 31-33 weeks (P less than 0.01). There was no difference at later ages. The spinal extension movement accompanying protective side turning of the head is age specific to the preterm infant. Individual rates of normal preterm development can be evaluated by longitudinal standardised examination. As a group, the infants with subsequent abnormal motor development showed delay at preterm age but this was not individually significant.

Cerebral Palsy↗
PubMed1985

Peripheral nerve conduction velocity and brainstem auditory evoked responses in small for gestational age preterm infants.

Ulnar nerve conduction velocity (NCV) and brainstem auditory evoked responses (BAER) were measured in each of 11 preterm small for gestational age (SGA) infants born at less than 35 weeks gestation. The mean motor NCV in the SGA infants was similar to that reported for infants who were appropriately grown for their gestational age (AGA). However, the mean central conduction time of the BAER in SGA infants was significantly shorter than that of AGA infants of the same post-menstrual age. Thus, the precocious development of auditory brainstem neural function in preterm SGA infants is not accompanied by changes in functional maturation of the peripheral motor nerves.

Brain Stem↗
PubMed1985

The influence of intra-uterine growth retardation on brainstem development of preterm infants.

This study examined brainstem function in 76 appropriate-for-gestational-age (AGA) and 25 small-for-gestational-age (SGA) infants born at less than 35 weeks gestation, using brainstem auditory evoked responses. During the preterm period the mean brainstem conduction time (BCT) of the 25 SGA infants was significantly shorter than that of AGA babies of the same gestation. The BCTs of the AGA infants decreased rapidly during postnatal development to term-equivalent age; those of the SGA infants did not change significantly. It is likely that prenatal factors are responsible for the alteration of early development in the neural function of non-asphyxiated SGA infants. This change in neural development may be important in determining later neurological performance.

Auditory Pathways↗
PubMed1985

Relation between apnoea duration and type and neurological status of preterm infants.

The incidence, duration, and type of apnoea were determined in 28 preterm infants born at 27 to 34 weeks' gestation, using polygraphic records of abdominal breathing movements and nasal airflow. Of the 1520 episodes of apnoea of 10 or more seconds duration, 1002 (66%) lasted 10 to 14 seconds, 311 (20%) lasted 15 to 20 seconds, and 207 (14%) lasted more than 20 seconds. Overall, 69% were central in type, 20% were mixed, and 11% were purely obstructive. With increasing duration of apnoea, the proportion of episodes of central apnoea decreased (69 to 29%) while that of mixed apnoea increased (20 to 60%). Eight infants had obstructive apnoea of more than 20 seconds duration. When they were compared with the 10 infants of similar gestational age and birthweight who had central or mixed apnoea, they had a higher incidence of intraventricular haemorrhage, hydrocephalus, positive pressure ventilation via an endotracheal tube, and abnormal neurological development during the first year of life.

Airway Obstruction↗