Biomedical subjects

E R Smith

Publications and source records attributed to E R Smith.

At least 199 records · Page 11Linked to original sources

PubMed1985

Reproductive physiology and behavior in the male rat following acute and chronic peripheral adrenergic depletion by guanethidine.

The effect of guanethidine, an adrenergic neuron blocking agent, on sexual behavior, penile reflexes, and spontaneous seminal emission (SSE) in the rat was studied by acute (i.e., 4 hours prior to testing) and daily IP injection of a low (5 mg/kg) and moderately high (25 mg/kg) dose of the drug. Acute low dose treatment eliminated the expulsion of a seminal plug with behavioral ejaculation without affecting sexual behavior; while acute high dose administration significantly decreased the number of intromissions preceding ejaculation and eliminated emission in copula and SSE for 3 days, with no evidence of retrograde ejaculation. Acute high dose treatment also increased the number of long flips displayed in the penile reflex test, and resulted in significant depression in plasma testosterone (T) and luteinizing hormone (LH) levels. Daily injection with the low dose eliminated emission in and ex copula for 4 weeks, without altering sexual behavior or penile reflexes. Seminal emission in copula reappeared more rapidly after stopping injections than SSE. Chronic high dose treatment was also without effect on copulatory activity. There was a partial recovery of emission in copula by the fourth week of treatment, suggesting that a nonadrenergic mechanism had assumed this function. In penile reflex tests conducted after 4 and 8 weeks, significantly fewer erections were displayed by drug-treated animals. During the period of initial recovery of emission in copula, emission during the reflex test was markedly increased, but SSE was decreased. Plasma T was significantly suppressed after two and four weeks of daily injections, but not thereafter, while plasma LH levels were not affected by the drug.

Animals↗

PubMed1985

Central effects of RDS-127: sexual behavior after intracerebroventricular administration and in vitro receptor binding studies.

RDS-127, in a dose-related manner, induced seminal emission ex copula after intracerebroventricular (i.c.v.) administration. In mating tests initiated 6 min after i.c.v. administration, RDS-127 induced decreases in ejaculation latency and intromission frequency, with some rats ejaculating on the initial intromission. Additionally, penile reflexes were eliminated by 150 micrograms and 600 micrograms, but not by an intermediate dose. In in vitro radioligand binding studies, RDS-127 potently displaced [3H]DPAT binding to 5-HT1A sites in rat cortex (Ki = 14 +/- 4 nM) and was only moderately effective in displacing [3H]spiperone binding to dopaminergic D2 sites in rat striatum. RDS-127 was essentially ineffective at 5-HT1B sites labeled by [3H]5-HT in rat striatum (Ki = 13 000 +/- 4 000 nM). These data demonstrate that centrally administered RDS-127 mimics the previously reported alterations in sexual behavior after systemic treatment and that RDS-127 is a high affinity 5-HT1A agent with low affinity at the 5-HT1B binding site.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1985

Obesity, acanthosis nigricans, insulin resistance, and hyperandrogenemia: pediatric perspective and natural history.

We studied the syndrome of acanthosis nigricans, obesity, insulin resistance, and hyperandrogenemia in 22 patients. Although isolated case reports in adolescents have appeared, this syndrome has not received full recognition as a pediatric entity. Our patients (17 girls, five boys) had a mean weight 5.7 SD above the mean for age, although mean height was only 0.5 SD above the mean for age. All patients had acanthosis nigricans. Their insulin resistance was significantly greater than that in a control group with comparable obesity. Fasting insulin concentration was 5.25 microU/ml in lean controls, 19.6 microU/ml in obese controls, and 49.8 microU/ml in study patients (P less than 0.002). Mean glucose disappearance rate during an insulin tolerance test was 6.7%/min in lean controls, 5.19%/min in obese controls, and 2.35%/min in study patients (P less than 0.02). After menarche, mean plasma testosterone concentration was 106 ng/dl, compared with less than 50 ng/dl in all lean and obese control patients. Data derived from our series of patients lead us to conclude that (1) this is a genetic syndrome, although the exact mode of inheritance is unclear; (2) the natural history of the syndrome invariably begins with the onset of obesity, followed by acanthosis nigricans that worsens with progressive weight gain; (3) acanthosis nigricans is thus a marker for hyperinsulinemia, which occurs before hyperandrogenemia; (4) hyperandrogenemia occurs only after menarche. Identification of this syndrome should permit monitoring for the development of hyperandrogenemia during puberty and determination of other affected family members.

Acanthosis Nigricans↗

PubMed1985

The pericardial hypothesis: a mechanism of acute shifts of the left ventricular diastolic pressure-volume relation.

Changes in LV diastolic P-V relations may be caused by changes in myocardial distensibility and by changes in extraventricular constraint. Experimental studies suggest that the upward shift of the LV diastolic P-V relation associated with pacing tachycardia, in patients with angina pectoris, is due to decreased myocardial distensibility which possibly represents incomplete relaxation. However, shifts in the LV diastolic P-V relation with vasodilator and vasoconstrictor agents seem to be caused by changes in extraventricular constraint. Experimental and clinical data show that such interventions do not significantly change the LV transmural P-V relation. This supports the hypothesis that these shifts are due to changes in pericardial pressure. Our data suggest that such vasoactive agents act by shifting blood between the (splanchnic) venous compartment and the heart, thereby changing heart size and in turn pericardial pressure. These concepts have significantly improved our understanding of the mechanisms of action of vasoactive agents. It seemed a paradox that vasodilators (e.g., nitroglycerine) could substantially lower filling pressure of the failing left ventricle without reducing cardiac output. Because of the downward-shift in the P-V relation with nitroglycerine, preload is virtually unchanged and therefore stroke volume is maintained. Appreciation of these phenomena has considerable impact on how haemodynamic measurements are interpreted. It is obvious that the use of LV end-diastolic pressure as an index of end-diastolic volume may lead to serious misinterpretations of ventricular function. Our demonstration that right atrial pressure might be used to assess pericardial pressure provides a potentially useful way to estimate LV transmural pressure, and therefore an accurate measure of preload.

Animals↗

PubMed1985

Conservative treatment of gastrointestinal haemorrhage.

The Gastroenterology Unit of the Royal Newcastle Hospital treats all acute bleeders in the hospital and has followed a policy of conservative blood transfusion and early surgery directed to gastric ulcer upon rebleeding. A prospective study of 201 consecutive episodes is presented and compared with recent series treated more conventionally. Our patients were transfused less, and operated upon less often with a lower mortality rate in those with chronic peptic ulcers. The data suggest that a reversion to the less aggressive treatment policies of several decades ago, combined with early limited surgery directed to endoscopically proven gastric ulcer is worthy of trial.

Acute Disease↗

PubMed1985

Evidence for the modulation of sexual behavior by alpha-adrenoceptors in male rats.

Clonidine, a commonly used antihypertensive agent believed to act by stimulation of central alpha-adrenoceptors, produced a dose-related suppression of ejaculatory behavior in sexually vigorous male rats throughout the range of treatment (0.0125-0.5 mg/kg). Treatment with 0.25 mg/kg virtually eliminated ejaculatory behavior, without altering the number of animals mounting and intromitting. These effects were maintained for at least 4 h after treatment. Prazosin, another antihypertensive (but acting by blockade of alpha 1-adrenoceptors), increased latencies to initiation of copulation, to ejaculation, and to reinstatement of copulation following ejaculation. Additionally, prazosin (1 mg/kg) pretreatment failed to attenuate or prevent the clonidine-induced suppression of ejaculation. In contrast, yohimbine, a drug which preferentially blocks alpha 2-adrenoceptors (2 mg/kg, 20 min prior to mating tests), caused a facilitation of copulatory behavior as evidenced by drastic decreases in ejaculation latency and intercopulatory and postejaculatory intervals. Pretreatment with yohimbine completely prevented the clonidine-induced suppression of ejaculation, while clonidine attenuated the facilitatory effects of yohimbine, suggesting a competitive interaction. These data lead to the suggestion that increased excitatory adrenergic activity results in increased sexual arousal either by blockade of alpha 2-or stimulation of alpha 1-adrenoceptors. Alternatively, stimulation of alpha 2-or blockade of alpha 1-adrenoceptors results in diminished sexual motivation. While the precise implications of this animal research for the clinic are as yet unclear, further research could lead to important developments in the pharmacological treatment of sexual dysfunctions.

Animals↗

PubMed1985

Assessment of pericardial constraint in dogs.

To determine the better method of measuring pericardial constraint, pericardial pressure was recorded by a liquid-filled open-ended catheter and a liquid-containing flat balloon in six open-chest anesthetized dogs. Left ventricular pressure was measured by a micromanometer-tipped catheter and left ventricular anteroposterior diameter was measured by sonomicrometry. Left ventricular end-diastolic pressure was raised to 20 +/- 1.7 (mean +/- SD) mm Hg by intravenous saline. Left ventricular diastolic pressure-diameter loops were constructed (1) with incremental amounts of saline (0 to 50 ml) in the resealed pericardium, (2) with several small holes in the pericardium, and (3) with the pericardium widely open. Measured pericardial pressures were compared with what was assumed to be the correct pericardial pressure, i.e., the calculated difference between left ventricular diastolic pressure (at a given left ventricular diameter) before and after opening the pericardium. Pressure recorded by the flat balloon was similar to the calculated pericardial pressure at all pericardial liquid volumes. Pressure recorded by the open-ended catheter, however, was significantly lower (p less than .05) than the calculated pressure unless there was at least 30 ml of liquid in the pericardium. After several holes had been made in the pericardium it still exerted a constraining effect, as shown by a marked rightward or downward shift of the left ventricular diastolic pressure-diameter relationships after completely opening the pericardium. After holes were made in the pericardium pressure recorded by the flat balloon was still similar to the calculated pericardial pressure. However, pressure recorded by the open-ended catheter was significantly (p less than .02) lower than the calculated pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Physical, metabolic, and hormonal effects on men of long-term therapy with medroxyprogesterone acetate.

Twenty-three men were treated with injectable medroxyprogesterone acetate (MPA) for sex-offending behavior. The physical, hormonal, and metabolic effects were monitored. The patients had significant (P less than 0.001) weight gain and increases (P less than 0.0001) in systolic blood pressure independent of weight gain. MPA therapy decreased testosterone (P less than 0.0001), luteinizing hormone (P less than 0.005), and testicular size (P less than 0.001), but not follicle-stimulating hormone. MPA's suppression of total sperm count was not consistent, but MPA significantly reduced sperm motility (P less than 0.001) and percent normal morphology (P less than 0.005). Statistically insignificant increases in insulin response without changes in glucose tolerance occurred in all patients, but only one patient developed overt diabetes mellitus. Three men developed gallstones, but none had significant changes in liver function. Patients receiving high-dose MPA therapy should be carefully monitored for blood pressure changes, diabetes mellitus, and gallbladder dysfunction.

Adult↗

PubMed1985

Sudden cardiac death: the search for a non-invasive means to detect the electrical substrate for the development of life-threatening cardiac arrhythmias.

Cardiovascular diseases remain the major cause of death in the adult North American population. Most of these deaths are sudden, occurring secondary to ventricular tachycardia/fibrillation (VT/VF). Based on the results of recent clinical trials, it seems likely that many of these deaths could be prevented if reliable means were available to select those patients at highest risk. To date, however, no totally satisfactory means to establish risk has been identified. The purpose of this paper is to review the currently utilized techniques and to draw attention to some new and potentially useful technology involving computer processing of surface recorded electrocardiographic (ECG) signals. ECG monitoring during rest and activity is neither sensitive nor specific. Invasive studies, using programmed ventricular stimulation to reproduce clinical arrhythmias, have proven extremely useful in the management of patients with recurrent VT/VF; this technique allows the selection of effective therapy as documented by subsequent inability to induce the arrhythmia. However, this technique does not have broad applicability given the complexity of these studies and the significant potential for morbidity. Recent efforts have focused on the detection of the abnormal electrical substrate giving rise to VT/VF by using body-surface electrocardiographic recording. Two approaches are being investigated. In one, high-gain, signal-averaged ECG signals are being utilized to detect (delayed) depolarization potentials occurring during the repolarization process - an electrophysiologic state known to give rise to re-entrant arrhythmias. Initial results with this technique are encouraging. We have focused on another approach - that of body-surface potential mapping.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

PubMed1984

Enhancement of sexual motivation in male rats by yohimbine.

Yohimbine hydrochloride, an alpha 2-adrenoceptor antagonist, increased sexual motivation in male rats as evidenced by increased mounting performance in mating tests conducted after genital anesthetization, increased percentage of male rats ejaculating in their first heterosexual encounter, and induction of copulatory behavior in sexually inactive male rats. These observations lead to the suggestion that alpha-adrenoceptors are important modulators of sexual arousal in intact male rats. These results indicate that pharmacological treatment of sexual (libido) dysfunction may be useful.

Animals↗

PubMed1984

Mechanism of action of nitrates. Role of changes in venous capacitance and in the left ventricular diastolic pressure-volume relation.

Nitroglycerin, when administered to patients with heart failure, causes a marked reduction in left ventricular filling pressure but often an increase in stroke volume and stroke work; based on the Frank-Starling principle, such a reduction in "preload" would be expected to result in a decrease in left ventricular end-diastolic volume and, therefore, a decline in stroke volume. Assessment of pressure-volume coordinates, however, has revealed that nitroglycerin produces a downward shift in the pressure-volume relationship. This apparent improvement in left ventricular compliance cannot be attributed to alterations in the elastic properties of the myocardium but rather appear to reflect a reduction in left ventricular external constraint. Recent animal and clinical investigations in our laboratory suggest that nitroglycerin causes venous dilatation (particularly in the mesenteric bed), thereby decreasing venous pressure at any given vascular volume. This decrease in cardiac filling pressure results in a decrease in heart size and, therefore, a reduction in pericardial pressure. Left ventricular transmural (intracavitary minus pericardial) pressure is little changed, however, so that end-diastolic volume and stroke volume are maintained.

Animals↗

PubMed1984

Sperm count, morphology and fluorescent body frequency in autopsy service workers exposed to formaldehyde.

A battery of monitoring tests that could indicate genetic damage was used to investigate occupational formaldehyde exposure in a population of a hospital autopsy service workers. 11 exposed individuals and 11 matched controls were evaluated for sperm count, abnormal sperm morphology and 2F-body frequency. Subjects were matched for sex, age and customary use of alcohol, tobacco and marijuana. Additional information was collected on health, medications and other exposures to toxins. 10 subjects were employed for 4.3 months (range 1-11 months) prior to the first sample and 1 was employed for several years. Formaldehyde exposures were episodic but with a time weighed average between 0.61 and 1.32 ppm (weekly exposure range 3-40 ppm X h). Exposed and control subjects were sampled 3 times at 2-3 month intervals. Sperm morphology was also evaluated in B6C3F1 mice after 5 daily oral doses of 100 mg/kg formalin. No increase in abnormal morphology was detected in the treated animals. In humans, no statistically significant differences were observed between the exposed and control groups for the observed variables. Reduced sperm count correlated with increased abnormal morphology and 2F-body frequency in the exposed group but not in the control group. Evaluation of the impact of incidental exposures suggests a reduced count with marijuana use and increased abnormal morphology with medications used by controls. No effects on sperm were seen from formaldehyde or its metabolites in this population after occupational exposure, nor in mice following a high acute exposure. It is possible that minor effects might have occurred. The lack of an effect in this study may be due to a lack of statistical power to detect effects at this exposure level.

Air Pollutants, Occupational↗

PubMed1984

Immunoreactive-beta-endorphin and LHRH levels in the brains of aged male rats with impaired sex behavior.

Levels of immunoreactive beta-endorphin and luteinizing hormone releasing hormone (LHRH) were measured in brain tissue of aged male Long-Evans rats. The animals were tested for sex behavior twice in one week at bimonthly intervals between the 7th and 27th month of life and were sacrificed along with a group of young (5-month old) sexually active rats. Thirty-one of the 89 rats which began the study remained healthy and tumor-free. By month 27, 21 of these had completely ceased to mate and 10 continued to show adequate sexual behavior. Diminished levels of beta-endorphin-like immunoreactivity were measured in the hypothalami and hindbrain of the old animals grouped together as compared to young animals and this reduction was shown to be significantly greater in hypothalamic tissue from the behaviorally inactive subgroup. Hypothalamic LHRH levels were not significantly altered by age in these animals. However, a marked reduction of LHRH content in the septal and midbrain regions of the aged-behaviorally inactive subgroup was evident when compared with the behaviorally active group. The data suggest that altered function of beta-endorphin and LHRH neurons of the aged brain may be involved in the behavioral deterioration observed in aged animals.

Aging↗

PubMed1984

Orthotopic ovarian transplantation in young and aged CBA mice.

Reproductive and hormonal changes associated with CBA mice which were orthotopically transplanted with ovaries from young or aged CBA mice were studied. Reproductive decline was defined by the number of mice mating and the number of implantation sites and resorptions in pregnant mice. A high percentage of resorptions was observed in aged mice receiving ovaries from young mice. An increase in the number of resorptions and a decrease in the number of implantation sites was observed in young mice transplanted with aged ovaries. Concentrations of LH, FSH and Prl were analyzed by radioimmunoassay from plasma of pregnant and nonpregnant transplanted mice, ovariectomized and sham-operated controls. Young ovariectomized mice had elevated concentrations of LH and FSH when compared to sham-operated controls. No differences were noted between the aged ovariectomized mice although the gonadotrophin levels in these animals were higher than those in comparable young groups. The highest LH and lowest FSH concentrations were found in young to young transplanted mice. The Prl concentrations in transplanted mice did not vary between groups. These data suggest that the hypothalamic-hypophyseal complex is functioning adequately in all transplanted groups and age-related changes in the ovary and uterus are responsible for embryonic mortality.

Aging↗

PubMed1984

Plasma and pituitary concentrations of LH, FSH and prolactin in aging Mongolian gerbils.

Samples of plasma and pituitary homogenates collected from female Mongolian gerbils (3-4, 11-13 and 20-25 month-old) at various stages of the estrous cycle were analyzed by radioimmunoassay for luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (Prl). Plasma and pituitary LH concentrations were similar in all three age groups. Plasma FSH concentrations tended to increase with age while plasma Prl concentrations remained unchanged. Pituitary concentrations of FSH and Prl were variable between the age groups depending upon the stage of the estrous cycle. The inability of older gerbils to produce young appears to result primarily from age-related changes occurring in the uterus rather than from alterations in the hypothalamic-hypophyseal complex.

Aging↗

PubMed1984

Temporal evolution of body surface map patterns following acute inferior myocardial infarction.

We studied the evolution of body-surface potential map (BSPM) patterns in 32 patients following first acute inferior myocardial infarction. Initial BSPMs were obtained at a mean of 79 hours post-infarction; follow-up BSPMs, a mean of eight months post-infarction. Temporal area-of-difference maps, constructed by subtracting initial from follow-up group-mean BSPMs, revealed reciprocal changes over the superior and inferior torso for both Q-zone and ST-segment time-integral distributions. The temporal changes in Q-zone patterns were small but definite: over the inferior torso there was a relative gain in Q-zone values and, over the superior torso, a relative decrease. In contrast, there were marked spatial and quantitative changes of ST-segment distributions during the follow-up period. Over the superior torso, particularly anteriorly, there was a gain in ST-segment values; over the inferior torso, a decrease. With the small temporal changes in Q-zone time-integral distributions, individual Q-zone maps continued to reflect a pattern of inferior myocardial infarction at follow-up. In contrast, the marked temporal changes in ST-segment time-integral distributions resulted in individual map patterns at follow-up that were nearly indistinguishable from normal ST-segment maps. The relatively small changes in depolarization time-integral patterns during the early post-infarction period suggest that the Q-zone patterns of the acute phase of myocardial infarction reflect near-irreversible or completed myocardial damage. The marked normalization of repolarization time-integral patterns during the recovery phase suggests, however, that there are also considerable areas of myocardium-at-risk during the early phase of the infarction process which stabilize with time.

Adult↗

PubMed1984

Seasonal aggression independent of seasonal testosterone in wood rats.

Levels of inter-male aggression, both in laboratory encounters and in the field, rise dramatically during the breeding season, closely paralleling the seasonal rise in testosterone. However, post-pubertally castrated males also show the dramatic seasonal rise in aggression in laboratory encounters with castrated opponents and show no decrement in fighting ability when paired with intact opponents, clearly demonstrating the independence of seasonal aggression from the proximate modulating effects of testosterone in wood rats.

Acclimatization↗

PubMed1984

Melatonin influences the reproductive physiology of male pallid bats.

Adult male pallid bats collected in July were maintained in photoperiods that provided 14 or 10 h of light/day (long or short days) and implanted subcutaneously with empty or melatonin-filled Silastic capsules. By early September, long-day bats treated with melatonin had smaller testes, larger accessory gland complexes and were more likely to have epididymal sperm than long-day bats which received empty capsules. In addition, in September, melatonin-treated animals weighed more than untreated animals. Melatonin simulates the effects of short days on testicular spermatogenesis and epididymal sperm storage in this species. We suggest that sensitivity to photoperiod in pallid bats, as in several other mammals, is mediated by the pineal gland.

Animals↗