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Biomedical subjects

C R Lake

Publications and source records attributed to C R Lake.

At least 163 records · Page 9Linked to original sources

Effect of acute volume alterations on norepinephrine and dopamine-beta-hydroxylase in normotensive and hypertensive subjects.

Fifty-six patients with essential hypertension and 29 normotensive controls were hospitalized and volume expanded with saline or volume depleted with furosemide. We measured plasma norepinephrine (NE) and dopamine-beta-hydroxylase (DBH) to evaluate their sympathetic nervous activity. NE and DBH levels and their response to volume changes were the same in normal and hypertensive subjects. Volume depletion increased plasma NE in recumbent subjects by 50% and in standing subjects by 75% but did not alter DBH. Volume expansion with 2 liters of normal saline did not generally alter plasma NE, but led to a small decrease in DBH. Hypertensives have normal plasma levels of NE and DBH and normal responses of NE and DBH to alterations in volume and posture. The human sympathetic nervous system increases NE output during volume depletion, but fails to decrease NE during volume expansion.

Adult↗

Cerebrospinal fluid norepinephrine in affective illness.

The authors measured cerebrospinal fluid norepinephrine concentrations in manic, depressive, and neurological control patients with and without probenecid administration. Baseline and probenecid norepinephrine values were significantly higher in manic than in depressed patients, who did not differ significantly from the neurological patients. Depressed patients with high levels of anxiety had higher levels of norepinephrine than those with low anxiety. These data suggest that alterations in mood or motor activity may be associated with changes in central norepinephrine metabolism in man.

Anxiety↗

Effect of handling and forced immobilization on rat plasma levels of epinephrine, norepinephrine, and dopamine-beta-hydroxylase.

Forced immobilization of rats triggers activation of adrenal-medullary discharge of epinephrine (EPI) and sympathetic neuronal release of norepinephrine (NE). Plasma levels of EPI reach peak values, which are about 40-fold greater than in undisturbed rats, at about 20 min and then decline to about one-third the peak levels. Plasma levels of NE are increased about 6-fold throughout the immobilization interval. Decapitation produces an 80-fold increase in plasma levels of EPI and an 8-fold increase in NE. These striking decapitation-induced increases are potentiated about 3-fold by immobilization, presumably as a consequence of an immobilization-induced alteration in the "set" of responsivity of spinal cord mechanisms controlling sympathoadrenal medullary discharge. Even minor disturbances produce highly significant increases in plasma EPI and NE and special precautions must be observed when studies involving plasma catecholamines or their effects are performed in animals.

Animals↗

Effects of smoking marihuana on left ventricular performance and plasma norepinephrine: studies in normal men.

In 14 healthy men we assessed the effects of smoking marihuana cigarettes containing 6 mg of delta-9-tetrahydrocannabinol on ultrasound measures of left ventricular function. Four of this group and four additional subjects also had measurements of plasma norepinephrine. Both heart rate and left ventricular performance (mean rate of internal diameter shortening [mean Vcf]) were significantly increased for at least 1 h after drug exposure compared with these values after placebo cigarettes. The immediate tachycardia and increase in mean Vcf were not accompanied by raised plasma norepinephrine levels. However, by 30 min after marihuana exposure, sympathetic neurotransmitter levels were significantly greater than both control values and those after placebo cigarettes, and they remained elevated for at least 2 h. Excessive sympathoadrenal discharge, as evidenced by augmented left ventricular function and prolonged catecholamine release, could adversely affect patients with heart disease.

Adult↗

Plasma noradrenalin and dopamine-beta-hydroxylase during behavioral testine of sexually deviant XYY and XXY males.

In a behavior study of a sexually deviant XYY and XXY male, who were both murderers, plasma noradrenaline (NAA), dopamine-beta-hydroxylase (DBH) were determined radioenzymatically under resting conditions and during exertional and emotional stress. Under a physical sork load on the bicycle ergometer both had normal plasma NA and DBH levels. During emotional stress both had NA increases of the same magnitude. During an arithmetic test NA values did not increase more than expected for the sitting position.

Adult↗

Lesch-Nyhan syndrome: low dopamine-beta-hydroxylase activity and diminished sympathetic response to stress and posture.

Patients with Lesch-Nyhan syndrome with virtually no hypoxanthine phosphoribosyltransferase activity demonstrate significantly low plasma activity of dopamine-beta-hydroxylase but normal basal levels of norepinephrine. Under conditions of emotional or postural stress the plasma concentrations of norepinephrine in Lesch-Nyhan patients increased less than in a normal population.

Adolescent↗

The sympathetic-nervous-system defect in primary orthostatic hypotension.

We sought to elucidate further the neurologic defect of idiopathic orthostatic hypotension, which appears to represent two distinct clinical entities. While recumbent, patients with multiple central-nervous-system defects, as well as peripheral autonomic nervous dysfunction, have normal plasma levels of norepinephrine that fail to increase normally after standing or exertion (P less than 0.001 by t-test as compared to controls). While recumbent, patients with peripheral autonomic insufficiency without signs of central-nervous-system defects have low levels of plasma norepinephrine (P less than 0.001) that also fail to increase normally after standing or exercising (P less than 0.001). Both groups have low levels of plasma dopamine-beta-hydroxylase (P less than 0.02). These findings are consistent with other pathological and pharmacologic observations suggesting that patients with central-nervous-system disease are unable to activate appropriately an otherwise intact sympathetic nervous system, whereas in patients without signs of central-nervous-system disease the deficit affects peripheral sympathetic nerves.

Adult↗

Increased norepinephrine levels and decreased dopamine-beta-hydroxylase activity in primary autism.

The sympathetic nervous system was evaluated in 11 primary autistic patients and their families. The plasma levels of norepinephrine (NE), the neurotransmitter of the sympathetic nervous system, was higher in the patients than in age-controlled normal volunteers both while supine and after standing. The plasma activity of dopamine-beta-hydroxylase, the enzyme that converts dopamine to NE, was significantly lower in the autistic patients and their healthy relatives than in control groups. Dopamine-beta-hydroxylase does not appear to provide an index of sympathetic activity in this group of patients who, on the basis of the elevated plasma levels of NE, may demonstrate a chronic state of hyperactivity of the sympathetic nervous system. Low enzyme activity found in both the autistic patients and their immediate families may be associated with this disorder.

Autistic Disorder↗

Reduction in plasma norepinephrine during fenfluramine treatment.

Plasma norepinephrine levels were reduced to 30% of placebo levels during the administration of fenfluramine, 120 mg/day, for 10 or more days. There was also a significant reduction in plasma dopamine beta-hydroxylase activity during fenfluramine treatment, suggesting that chronic administration may induce antiadrenergic effects which may be useful in the treatment of disorders affected by circulating catecholamines.

Adult↗

Lack of correlation of plasma norepinephrine and dopamine-beta-hydroxylase in hypertensive and normotensive subjects.

Dopamine-beta-hydroxylase (DBH) and norepinephrine (NE) have been determined in over 350 plasma samples from 174 subjects while resting supine (basal sample), standing, or exercising. Although increments in both NE and DBH were found with postural change, the further increase in plasma levels of NE during exertion was not attended by any change in levels of DBH. There was no significant correlation between basal levels of DBH and NE nor was there any correlation in their increments after standing or exercising. DBH activity in plasma of subjects with moderate essential hypertension was not different from that of normotensive subjects. It is concluded that plasma DBH is a poor index of acute sympathetic neuronal activity.

Blood Proteins↗

Increased sympathetic nervous system activity in alcoholic patients treated with disulfiram.

The authors measured plasma levels of norepinephrine (NE) and dopamine beta-hydroxylase (DBH), pulse rates, and blood pressures of 81 hospitalized alcoholic patients. Treatment with 500 mg/day of disulfiram (but not 250 mg/day or placebo) resulted in small but significant increases in plasma NE and in blood pressure. The 500-mg dose did not appreciably inhibit DBH. Patients receiving high doses of disulfiram should have their blood pressure monitored and their dose decreased to 250 mg/day when possible.

Adult↗

Catecholamine metabolism in Gilles de la Tourette's syndrome.

Abnormal central catecholamine neurotransmission has been suggested in Gilles de la Tourette's syndrome. The authors evaluated the sympathetic nervous system in both the basal state and in its responsivity to postural and exercise stress. Plasma norepinephrine and the activities of its synthetic and degradative enzymes were not different in 33 Tourette patients, a control group of unaffected relatives, and another control group of unrelated healthy volunteers. This finding suggests that these patients have neither a generalized dysfunction of norepinephrine metabolism nor a defect in the central control of sympathetic function.

Adolescent↗

Newborn dopamine-beta-hydroxylase, minor physical anomalies, and infant temperament.

The authors examined newborn anomaly scores for 193 normal infants in relation to obstetrical history, newborn dopamine-beta-hydroxylase (DBH), and 5-month (N=185) and 1-year (N=123) infant behavior, determined by a questionnaire completed by their mothers. There was no significant relationship between anomaly score and obstetrical history or 5-month infant temperament; low significant correlations were found between newborn DBH and 1) infant irritability and unsociable response and 2) 1-year anomaly scores and reported activity levels. The authors discuss the possible importance of these findings.

Child Behavior↗

Cerebrospinal fluid norepinephrine alterations during electrical stimulation of cerebellar, cerebral surfaces in epileptic patients.

Lumbar cerebrospinal fluid norepinephrine concentrations were determined by radioenzymatic assay in five epileptic patients receiving double-blind cerebellar stimulation and in three epileptic patients with subdural cerebral surface electrodes. Mean CSF norepinephrine levels were significantly elevated by chronic cerebellar stimulation and significantly depressed after intermittent cerebral cortical stimulation. Lumbar CSF cyclic adenosine monophosphate levels determined by radioimmunoassay were not significantly altered by either cerebellar or cerebral surface stimulation. Our study suggests that (1) electrical stimulation of the anterodorsal cerebellum in man evokes alterations in noradrenergic metabolism. Cerebellar stimulation-induced elevations in norepinephrine may inhibit cerebellar, cerebral, and spinal neuronal activity. In addition, (2) noradrenergic responses to brain surface stimulation may exhibit regional specificity, and (3) noradrenergic alterations evoked by cerebral surface stimulation may not mimic those induced in isolated brain preparations.

Adolescent↗

Neurophysiological and neurochemical alterations during electrical stimulation of human caudate nucleus.

Lumbar cerebrospinal fluid (CSF) norepinephrine (NE) concentrations were preoperatively determined in five patients using a radioenzymatic assay technique. Stereotaxic thalamotomy was performed using depth coagulating electrodes with stimulating points at 5.0-mm intervals along the shaft. No significant alterations in prestimulation lumbar CSF NE levels were noted 12 days after electrode installation. Stimulating points within the caudate nucleus were anatomically localized using ventricular landmarks and stimulation-induced neurophysiological responses were recorded. Twelve hours after intermittent electrical stimulation of the caudate nucleus, lumbar CSF NE concentrations were significantly decreased. Our data suggest the presence of noradrenergic pathways in man that are inhibited by caudate nucleus stimulation.

Adolescent↗