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Biomedical subjects

H E Edwards

Publications and source records attributed to H E Edwards.

At least 19 recordsLinked to original sources

Gonadectomy unmasks an inhibitory effect of progesterone on amygdala kindling in male rats.

Previous studies have suggested that the effects of progesterone on kindling in rats may be sexually differentiated, significant effects of physiological levels of progesterone being observed only in females. The present study demonstrates that this difference results from the hormones secreted by the testes. Thus, in orchidectomized males, progesterone induces a delay in the onset of amygdala-kindled seizures similar to that observed in females.

Amygdala↗

Improving pain management by nurses: A pilot Peer Intervention Program.

Significant pain continues to be reported by many hospitalized patients despite the numerous and varied educational programs developed and implemented to improve pain management. A theoretically based Peer Intervention Program was designed from a predictive model to address nurses' beliefs, attitudes, subjective norms, self-efficacy, perceived control and intentions in the management of pain with p.r.n. (as required) narcotic analgesia. The pilot study of this program utilized a quasi-experimental pre-post test design with a patient intervention, nurse and patient intervention and control conditions consisting of 24, 18 and 19 nurses, respectively. One week after the intervention, significant differences were found between the nurse and patient condition and the two other conditions in beliefs, self-efficacy, perceived control, positive trend in attitudes, subjective norms and intentions. The most positive aspects of the program were supportive interactive discussions with peers and an awareness and understanding of beliefs and attitudes and their roles in behavior.

Adult↗

Determinants of nurses' intention to administer opioids for pain relief.

A statewide cross-sectional survey was conducted in Australia to identify the determinants of registered nurses' intention to administer opioids to patients with pain. Attitudes, subjective norms and perceived control, the key determinants of the Theory of Planned Behavior, were found to independently predict nurses' intention to administer opioids to these patients. Perceived control was the strongest predictor. Nurses reported positive overall attitudes towards opioids and their use in pain management. However, many negative attitudes were identified; for example, administering the least amount of opioid and encouraging patients to have non-opioids rather than opioids for pain relief. The findings related to specific attitudes and normative pressures provide insight into registered nurses' management of pain for hospitalized patients and the direction for educational interventions to improve registered nurses' administration of opioids for pain management.

Attitude of Health Personnel↗

Fever management practises: what pediatric nurses say.

Pediatric nurses manage fevers in hospitalized children daily: a complex practise. The present study identified varied decision-making criteria and inconsistent practise influenced by many external variables. Nurses perform comprehensive assessments in order to make informed decisions. However, factors influencing their practise include medical orders, the temperament of the child, a history of febrile convulsions, parental requests, colleagues and ward norms. Nurses have a 'temperature' at which they consider a child febrile (37.2-39.0 degrees C) and many reported a 'temperature' at which they administered antipyretics (37.5-39.0 degrees C). Antipyretics were administered to febrile children for pain relief, irritability, at the request of parents and to settle a child for the night. Administration was reported to be higher during the day and evening shifts, at medication rounds and when the ward was busy. At night, nurses were reluctant to wake a sleeping febrile child, preferring to observe them instead. Recommendations to promote consistent fever management practises are included.

Analgesics, Non-Narcotic↗

Evaluating student learning: an Australian case study.

Determining the quality of student learning is an ongoing challenge to all educators. However, for educators and students in the health professions, evaluation of learning takes on a different dimension in terms of ensuring that graduates are competent, and thus safe, practitioners. This paper outlines the processes and methods by which student learning has been evaluated throughout a 22-year period at a large school of nursing in a Australian university. First, a historical overview of the major methods used demonstrates how relevant educational theories and sociopolitical forces and movements have influenced the whole curriculum including evaluation methods. Second, examples of current evaluation methods for undergraduate clinical and theoretical units are described. Reflections about past successes and future challenges conclude the paper.

Australia↗

The impact of corticosteroids on the developing animal.

Infants are subjected to both endogenous and exogenous corticosteroids in the pre- and postnatal periods. Stress to the mother before birth, or to the child postpartum, can give rise to high, chronic endogenous corticosteroid levels caused by activation of the hypothalamic-pituitary-adrenal (HPA) axis. Physician-administered exogenous corticosteroids are also used in the management of a wide spectrum of pre- and postnatal conditions. The long-term effects of corticosteroids in developing humans are not well known. Studies in animals, however, indicate that both natural stress and exogenous corticosteroids can have long-lasting and deleterious effects on the body, brain, behavior, and hypothalamic-pituitary-adrenal axis of developing infants. These data suggest that exogenous corticosteroids should be administered with caution, after careful benefit/risk analyses, and that, as far as possible, the developing brain should be protected against the effects of pre- and postnatal stress.

Adrenal Cortex Hormones↗

The effect of seizures and kindling on reproductive hormones in the rat.

Reproductive dysfunction and endocrine disorders are common among both women and men with epilepsy, and, in particular, with temporal lobe epilepsy. In clinical studies, it is hard to separate the effects of seizures from the effects of medication and life style. Studies in rodents, however, suggest that seizures per se can contribute to reproductive dysfunction. In female rats, generalized seizures disrupt normal ovarian cyclicity in adults, and repeated electroshock seizures delay the onset of puberty in juveniles. Right amygdala kindling in adult female rats causes acyclicity, the development of polycystic ovaries and premature aging of the hypothalamic-pituitary neuroendocrine axis, leading to chronic anovulation and continuous estrogen exposure. In adult male rats, repeated electroshock seizures result in transient hypogonadism, characterized by decreased serum testosterone levels and lowered gonadal tissue weight. In contrast, right amygdala kindling increases serum testosterone, estradiol levels and gonadal weight. These findings suggest that reproductive dysfunction in women and men with epilepsy may result from recurrent seizure activity, due to seizure-related interference with the normal functions of the hypothalamic-pituitary-gonadal axis.

Animals↗

Progestin receptors mediate progesterone suppression of epileptiform activity in tetanized hippocampal slices in vitro.

Clinical and laboratory studies suggest that progesterone reduces epileptic seizure activity. The mechanisms underlying this effect are not known. The present study determined the effects of progesterone on extracellular evoked responses recorded in the CA1 field of hippocampal slices, as well as epileptiform responses recorded from tetanized slices. Slices were prepared from ovariectomized rats, with or without estrogen replacement. Hippocampal slices were superfused in vitro with one of the following treatments: progesterone with or without RU486 (a progesterone receptor antagonist); allopregnanolone (a progesterone metabolite that potentiates GABA action at GABA(A) receptors); RU5020 (a high-affinity progesterone receptor agonist); or cholesterol (control). In non-tetanized slices, a twofold increase in the excitatory postsynaptic field potential and population spike amplitude occurred during both cholesterol and progesterone superfusion. In contrast, under the same conditions, exposure to allopreganolone caused a 25% reduction in both field potential and population spike amplitude of evoked responses within 30min of treatment. In tetanized slices, progesterone and RU5020, but not allopregnanolone or cholesterol, caused significant reductions in the field potential and population spike amplitude of evoked responses. Progesterone and RU5020 also significantly reduced the duration of tetanic stimulus-induced afterdischarges and the frequency of spontaneous interictal discharges. The effects of allopregnanolone were restricted to a reduction in the primary afterdischarge duration. Estrogen replacement slightly attenuated progesterone's suppression of spontaneous discharges and depression of evoked responses. All responses to progesterone were blocked by prior or concurrent exposure to RU486. These data indicate that allopregnanolone suppresses evoked potentials in non-tetanized hippocampal slices, consistent with previous reports that this neurosteroid has marked anxiolytic and anticonvulsant effects. After tetanization, however, progesterone receptor-mediated responses become quantitatively more important as a mechanism for suppressing hippocampal electrical activity.

Animals↗

Steroid hormones affect limbic afterdischarge thresholds and kindling rates in adult female rats.

UNLABELLED: Catamenial epileptics show particular vulnerability to seizures during menstruation and at the time of ovulation, when circulating estradiol (E(2))/progesterone (P(4)) ratios are high. The present study tested the hypothesis that alterations in neuronal excitability induced by E(2) and P(4) affect thresholds and the development of secondary generalization in kindled rats. METHODS: The effects of endogenous hormones secreted during the estrous cycle, and of exogenous exposure to E(2) and P(4) after ovariectomy (OVX), with and without adrenalectomy (ADX), were tested. Kindling electrodes were implanted in the basolateral amygdala or dorsal hippocampus in adult female rats. The anticonvulsive effects of P(4) on amygdala kindled seizures were also determined in intact subjects. RESULTS: In intact females, afterdischarge thresholds (ADTs) in the amygdala were significantly lower (306+/-48 microA; peak to peak) at mid-day proestrus, just prior to ovulation, when serum E(2) is elevated. ADTs were more than twofold higher (808+/-95 microA) during metestrus, coincident with peak ovarian P(4) secretion. In OVX females, amygdala thresholds were lowest with E(2) replacement and highest with P(4) replacement. Hippocampal ADT was unaffected by hormone replacement after OVX. The rates of both amygdala and hippocampal kindling were significantly accelerated by E(2) and slowed by P(4). E(2) replacement significantly increased serum corticosterone (CORT) levels. In ADX rats, CORT replacement increased kindling rates, synergizing with the effects of E(2). In fully kindled animals, P(4) administration suppressed motor seizures in approximately 60% of cases. CONCLUSIONS: E(2) lowers amygdala ADTs and facilitates kindling. This effect may involve both direct E(2) effects and indirect effects mediated via increased levels of circulating corticosterone. P(4) raises amygdala ADTs, slows kindling development and suppresses fully kindled seizures. Hence, P(4) may have potential therapeutic value for women with catamenial epilepsy.

Amygdala↗

Testosterone and its metabolites affect afterdischarge thresholds and the development of amygdala kindled seizures.

UNLABELLED: In boys with epilepsy, pubertal increases in seizure frequency may be associated with rising androgen levels. The present study tested the hypothesis that testosterone (T) and/or its metabolites might affect amygdala seizure thresholds and the development of secondary generalization from amygdala foci (kindling). Afterdischarge thresholds and kindling rate were measured in gonadectomized (GDX) male rats, with or without T replacement therapy. Drugs that block either androgen or estradiol (E(2)) receptor-mediated responses were also tested. METHODS: Kindling electrodes were implanted in the basolateral amygdala of adult male Wistar rats. In Experiment 1, subjects were GDX and implanted with a silastic capsule containing either: cholesterol (control); T; 5% E(2) in cholesterol; or 5alpha-dihydrotestosterone (DHT). In Experiment 2, intact subjects were treated with daily injections of vehicle (control); daily injections of flutamide (an androgen receptor antagonist); or Silastic implants containing 1,4,9-androstatriene 3,17-dione (ATD; an aromatase inhibitor). RESULTS: In Experiment 1, initial afterdischarge (AD) thresholds were significantly lowered by E(2) treatment, as compared to cholesterol controls, and remained low throughout the kindling paradigm. In T replaced males, AD threshold significantly decreased over the kindling period, a response that was not observed in DHT treated rats. Rates of kindling were significantly faster as a result of T, E(2) and DHT treatment, as compared to cholesterol controls. E(2) treated males kindled the fastest of all 3 groups. In Experiment 2, initial AD thresholds were significantly lowered by flutamide treatment, as compared to cholesterol controls, and remained low throughout the kindling paradigm. AD threshold significantly decreased over the kindling period in intact males, a response that was blocked by ATD treatment. Both flutamide and ATD significantly slowed the rate of kindling, as compared to intact controls. ATD had the most dramatic inhibitory effect on kindling rate. CONCLUSIONS: In males, T and its two metabolites, E(2) and DHT, all appear to enhance the development of amygdala-kindled seizures. E(2) has the most potent epileptogenic effect. Antagonism of E(2) mediated effects in the brain may have potential therapeutic value for males with epilepsy.

Amygdala↗

Limbic seizures alter reproductive function in the female rat.

PURPOSE: Reproductive dysfunction and endocrine disorders are common among women with temporal lobe epilepsy. This study used the kindled rat model to test the hypothesis that limbic seizures directly contribute to reproductive dysfunction. METHODS: Kindling electrodes were implanted in the basolateral amygdala in adult female rats. Females were kindled by either brief, daily, suprathreshold stimulations with a bipolar electrode or sham-kindled (controls). Electrographic and behavioral seizures were monitored. Estrous cycles also were monitored with daily vaginal smears. RESULTS: Seizures arrested ovarian cyclicity in all (n = 42) kindled animals, the rats exhibiting persistent vaginal cornification (PVC). In these animals PVC was associated with high serum estradiol, increased pituitary weight, and polyfollicular ovaries consisting of many cystic follicles, as well as follicles in various stages of growth and atresia. In 93% of females, this effect occurred after the development of stage 5 motor seizures, when focal seizures had secondarily generalized. In contrast, only five (21%) of 24 sham-kindled controls exhibited PVC. A single injection of progesterone (P4) temporarily restored cyclicity in five (18%) of 28 kindled females exhibiting PVC. In contrast, P4 administration restored cyclicity in all five sham-kindled controls that had spontaneously stopped cycling. P4 treatment to kindled females in PVC resulted in a different endocrine profile than that in non-P4-treated, kindled rats in PVC. P4-treated rats had high serum estradiol, testosterone, and prolactin levels; they showed an increase in pituitary weight; and their ovaries contained numerous corpora lutea and cystic follicles surrounded by markedly overdeveloped thecal cell layers. CONCLUSIONS: Seizures initiated in the amygdala result in impairment of the hypothalamic-pituitary axis, resulting in loss of ovarian cyclicity.

Amygdala↗

Partial and generalized seizures affect reproductive physiology differentially in the male rat.

PURPOSE: Reproductive dysfunction and endocrine disorders occur frequently among men with epilepsy. This study tested the hypothesis that focal limbic seizures and generalized seizures may both contribute to reproductive dysfunction. METHODS: The rat kindling model was used to mimic focal limbic seizures. Kindling electrodes were placed in the basolateral amygdala. Male rats were either intact, gonadectomized (GDX) or GDX + testosterone (T) replaced and then kindled. Controls were left intact and sham-kindled. Maximal electroconvulsive shock (MES) treatment was used to model generalized seizures, by using eight stimulations, one every other day, for 2.5 weeks. Animals were killed either 3 h or 6 weeks after MES treatment to determine short- and long-term effects. RESULTS: Kindled seizures resulted in an increase in serum testosterone, estradiol, and prolactin in intact males, accompanied by a significant increase in testis, epididymis, and pituitary weight, as well as a significant decrease in prostate weight. MES treatment caused a short-term reduction in serum testosterone and testis, epididymis, and prostate weight. All parameters were restored to control values within 6 weeks of the last MES seizure, with the exception of pituitary weight and serum prolactin, which remained significantly elevated 6 weeks after MES treatment. CONCLUSIONS: Our results indicate that both focal limbic (amygdaloid) seizures and generalized MES seizures disturb normal reproductive physiology in the male rat. Amygdaloid-kindled seizures have mixed effects on different parameters of reproductive function, whereas MES seizures induce a transient hypogonadal state. These results suggest that reproductive dysfunction in men with epilepsy may result from seizure-related interference with the normal functions of the hypothalamic-pituitary-testicular axis.

Amygdala↗

Reproductive aging in the Djungarian hamster, Phodopus campbelli.

Changes in fertility (delivery success), fecundity (litter size and weaning success), sensitivity to pregnancy-blocking stimuli (mate removal after 24 h), and hypothalamic-pituitary-ovarian function were assessed during reproductive aging in the Djungarian hamster, Phodopus campbelli. All indices of aging occurred earlier in the Djungarian hamster than they do in other laboratory models, including the mouse. Fertility and fecundity were halved by 8 mo of age, and the response to pregnancy-blocking stimuli disappeared by 4-6 mo. Pup birth weight increased with maternal age and decreasing litter size. Older females also tended to lose entire litters rather than to reduce litter size and successfully wean remaining pups. Impaired ovarian function was a major contributor to reproductive aging. Numbers of large antral follicles developing in aged females and in aged females receiving eCG treatment were similar to those in young females. However, a few preovulatory follicles routinely failed to ovulate from each ovary. Healthy preovulatory follicles in old females secreted the large quantities of estradiol-17 beta typical of estrous cycles, but eCG-induced preovulatory follicles did not. As young females of this species have smaller folicular reserves than other rodent species, and follicle numbers in older females are further reduced (with a high incidence of completely degenerate ovaries), follicular exhaustion was coincident with reproductive failure. Neuroendocrine aging of the hypothalamus was also implicated in the loss of a pregnancy-blocking response and the failure of maternal care with increasing maternal age. Similarities to reproductive aging in long-cycle species (including primates) suggest that the Djungarian hamster is a useful laboratory model that deserves further investigation.

Aging↗

Daily patterns of pituitary prolactin secretion and their role in regulating maternal serum progesterone concentrations across pregnancy in the Djungarian hamster (Phodopus campbelli).

Profiles of serum prolactin (PRL) and progesterone (P4) were determined in repeatedly (every 2 h) sampled female Djungarian hamsters (Phodopus campbelli) over a 24-h period on Days 3, 6, 9, 12, and 15 of the 18-day pregnancy. The first half of pregnancy was characterized by significant surges of PRL within a 2-h period around dawn (0500 h) and dusk (1900 h), with some females also showing a weak midday surge at 1300 h. By Day 9, dusk and midday surges were absent, but the dawn surge remained at its initial amplitude. On Day 12, no PRL surges were seen. Resumption of both the dusk and dawn PRL surges occurred on Day 15 of gestation. Considerable interindividual variability in the amplitude of PRL surges, the timing of PRL surges, and the number of surges per day was detected and would complicate any assessment of PRL levels based on single samples per female. Serum P4 concentrations were 8-10 ng.ml-1 before doubling on Day 15. A 3-day treatment of 50 and 300 micrograms bromocryptine (CB 154; on Days 13-15) effectively suppressed PRL during late pregnancy (Day 15) but did not alter serum P4 concentrations or interfere with parturition. Therefore, surges of PRL are not an essential luteotropic stimulus during late gestation. Compared to oil-injected controls, CB 154-treated females had a higher incidence of infanticide postpartum. Growth rates of the pups, mammary gland development, and successful delivery of milk to pups, however, did not differ between groups. Further studies will be required to determine the function of late-gestation PRL surges.

Animals↗

Spontaneous termination of an induced pseudopregnancy in the Djungarian hamster, Phodopus campbelli.

The mechanisms which underlie the termination of a functional pseudopregnancy and the return to a behavioral estrus in the Djungarian hamster, Phodopus campbelli, were investigated through changes in (1) serum prolactin concentrations; (2) progesterone and estradiol concentrations in the serum and extracted corpus luteum, ovulatory follicle, and non-luteal portion of the ovary; and (3) corpus luteum and non-luteal ovary weight. Females were asynchronous in the timing of resumption of behavioral estrus, ranging between Days 9 and 11 postcoitus with the mode on Day 10. Unlike proestrus of a cycle, mating following a pseudopregnancy was associated with a large surge of progesterone in serum. Early pseudopregnancy was characterized by high pulsatile changes in serum prolactin, stable serum and corpus luteum progesterone, low concentrations of serum and ovarian estradiol, and high, stable corpus luteum weight. Although the day of return to behavioral estrus varied across females, there was synchrony between females in the timing of regression of corpus luteum function and structure. Serum prolactin and progesterone levels significantly decreased by Day 7 but were not followed by a decrease in corpus luteum progesterone content until Day 8. Changes in luteal function were also uncoupled from changes in weight since luteal weight remained high through Day 8 before disappearing from the ovary by Day 9. The pattern and level of prolactin surges during pseudopregnancy is the same as that seen during pregnancy, suggesting that the termination of coitally induced pituitary prolactin surges is spontaneous.

Animals↗

Endocrinology of the pregnant Djungarian hamster Phodopus campbelli.

Factors regulating maternal serum progesterone concentrations during pregnancy in the Djungarian hamster Phodopus campbelli were investigated through changes in (1) concentrations of progesterone and oestradiol in the serum and extracted corpus luteum, non-luteal ovary, and placenta during late pregnancy, (2) prolactin concentrations in the serum, and (3) mass of the fetus, placenta, corpus luteum and non-luteal ovary. Early pregnancy (days 1-4) was characterized by surges of prolactin, corpus luteum growth and increased corpus luteum activity as indicated by increases in luteal mass, progesterone content and serum progesterone concentration. During mid-pregnancy (days 8-11) there was a loss of prolactin surges and a halt in the growth of the corpus luteum, as indicated by stable luteal mass, progesterone content and serum progesterone concentrations that were comparable with those of day 4 of pregnancy. At the same time, the non-luteal ovary began to secrete oestradiol and, on day 12, preovulatory follicles of unknown function were found. During late pregnancy (days 14-17), the prolactin surge pattern was re-established, the non-luteal ovary and corpus luteum contained oestradiol, luteal cell growth caused an increase in corpus luteum size and mass, and serum progesterone concentrations doubled. As late-term pregnancies failed to survive bilateral ovariectomy and the placenta contained little extractable progesterone, it appears that the progesterone of Djungarian hamster pregnancy is synthesized by the corpus luteum throughout gestation.

Animals↗

Induced components in the spontaneous ovulatory cycle of the Djungarian hamster (Phodopus campbelli).

Although Djungarian hamsters, Phodopus campbelli, show regular, 4-day spontaneous estrous cycles when tested for behavioral receptivity, this study shows that over 50% of 624 virgin females paired with males show their first behavioral estrous on the third day after pairing. The observed pattern is compared against predictions of estrous synchrony and/or estrous cycle suppression models. They fail to explain the high incidence of mating on the third day, and are incompatible with our current understanding of the natural history of the species. An alternative hypothesis, that Djungarian hamsters fail to cycle in the absence of a male, but are rapidly induced into a succession of 4-day cycles by his presence, appears to explain both the pattern of matings and earlier observations that estrous cycles could not be monitored by vaginal smear or lavage, only by interactions with a male. These analyses, thus, conclude that Djungarian hamster females may require a signal from a male to initiate and maintain successive 4-day estrous cycles.

Animals↗

Prediction of high blood pressure in young people: the limited usefulness of parental blood pressure data.

Blood pressure was measured in 864 young people aged 16-24 years, 8 years after both of their parents had their blood pressures measured as part of the screening phase of the Medical Research Council Mild Hypertension Trial. Only 29% of offspring with a conventional 'family history of hypertension', defined in terms of having at least one parent with a score in the top 10% of the distribution, had a blood pressure score in the top 20% after 8 years. The positive predictive value was increased to 38% in offspring with two parents in the top 20%, but only 4% of offspring met this definition and only 7% of offspring in the top 20% after 8 years were identified by this method. Sensitivity was increased to 46% in offspring with at least one parent in the top 20%, but 33% of offspring met this definition and 74% of them did not have a blood pressure level in the top 20% after 8 years. It is concluded that parental blood pressure data are of limited value for the prediction of high blood pressure in young people and provide no scientific basis for a high risk strategy of prevention.

Adolescent↗