Search PubMed⌕ Search

Biomedical subjects

A J Lewy

Publications and source records attributed to A J Lewy.

At least 19 recordsLinked to original sources
PubMed1992

Sleep propensity free-runs with the temperature, melatonin and cortisol rhythms in a totally blind person.

In previous studies, we found that many totally blind people have free-running melatonin rhythms, but that free-running melatonin rhythms were not necessarily associated with periodic insomnia and daytime sleepiness. Thus, it was not clear if the circadian sleep propensity rhythm was free-running with the other circadian rhythms. In the present study, we report that the sleep propensity rhythm (as defined by an ultrashort sleep-wake schedule) free-ran with the melatonin, temperature and cortisol rhythms in a 44-year-old totally blind man even though he maintained a conventional sleep schedule and did not complain of clinically significant insomnia or excessive daytime sleepiness.

Adult↗
PubMed1992

Melatonin rhythms in night shift workers.

For some time, it has remained uncertain whether the circadian rhythms of permanent night shift workers are adapted to their night-active schedule. Previous studies of this question have often been limited by "masking" (evoked) effects of sleep and activity on body temperature and cortisol, used as marker rhythms. In this study, the problem of masking was minimized by measuring the timing of melatonin production under dim light conditions. Nine permanent night shift workers were admitted to the Clinical Research Center (CRC) directly from their last work shift of the week and remained in dim light while blood samples were obtained hourly for 24 hours. Melatonin concentrations were measured in these samples using a gas-chromatographic mass-spectrometric method. Sleep diaries were completed for two weeks prior to the admission to the CRC. Overall, the onset of the melatonin rhythm was about 7.2 hours earlier (or 16.8 hours later) in the night workers compared to day-active controls. It was not possible to know whether the phase of the melatonin rhythm was the result of advances or delays. In night shift workers, sleep was initiated (on average) about three hours prior to the onset of melatonin production. In contrast, day-active subjects initiated sleep (on average) about three hours after their melatonin onset. Thus, the sleep times selected by night shift workers may not be well-synchronized to their melatonin rhythm, assumed to mark the phase of their underlying circadian pacemaker.

Adult↗
PubMed1992

Circadian rhythm abnormalities in totally blind people: incidence and clinical significance.

When people are completely isolated from environmental time cues, their circadian rhythms free run with a nearly 24-h cycle, generated by an internal body clock. Free-running temperature, cortisol, and melatonin rhythms have also been described in totally blind people, even though they were living in normal society and had access to abundant time cues; thus an intact visual system may be essential for synchronization of the circadian system. However, because of the small numbers of subjects studied, the incidence and clinical significance of circadian rhythm abnormalities among the blind has remained uncertain. In this study, plasma melatonin (n = 20), cortisol (n = 4), and sleep propensity (n = 1) were measured in serial samples taken from totally blind subjects for 24 h. Most totally blind subjects had circadian rhythm abnormalities. In about half of the subjects, the rhythms were free-running. Some blind subjects suffered recurrent insomnia and daytime sleepiness that were maximal when the internal rhythms were out of phase with the preferred sleep times. The high incidence of abnormal circadian rhythms in blind people underscores the importance of the light-dark cycle as an important environmental synchronizer for the human circadian system.

Biological Clocks↗
PubMed1992

Melatonin shifts human circadian rhythms according to a phase-response curve.

A physiological dose of orally administered melatonin shifts circadian rhythms in humans according to a phase-response curve (PRC) that is nearly opposite in phase with the PRCs for light exposure: melatonin delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening. The human melatonin PRC provides critical information for using melatonin to treat circadian phase sleep and mood disorders, as well as maladaptation to shift work and transmeridional air travel. The human melatonin PRC also provides the strongest evidence to date for a function of endogenous melatonin and its suppression by light in augmenting entrainment of circadian rhythms by the light-dark cycle.

Adult↗
PubMed1991

The effects of shifting sleep two hours within a fixed photoperiod.

This study examined the effects of shifting the time of sleep within a constant photoperiod on the circadian rhythms of body temperature and melatonin secretion. Subjects lived under conditions of a long scotoperiod (dim light of less than 10 lux from 6 p.m. until 8 a.m.) for three weeks. In order to delineate dawn and dusk, subjects received one hour of bright light (2500 lux) before and after the scotoperiod (i.e., from 8 to 9 a.m. and from 5 to 6 p.m.). For the first week of the experiment they slept from 10 p.m. until 6 a.m. In the second week, sleep was advanced two hours; that is, subjects retired at 8 p.m. and arose at 4 a.m. The third week was a repeat of the first, resulting in a two-hour delay of sleep from week two to three. The six subjects who successfully completed this protocol had no significant changes in the timing of the body temperature minima and onset of secretion of melatonin. This indicates that the timing of allowed sleep has less of an immediate effect on circadian rhythms than the timing of the external light-dark cycle. The circadian effects of the timing of sleep may be due more to the light-dark cycle that is imposed by the sleep-wake cycle than from the timing of sleep itself.

Adult↗
PubMed1991

Melatonin administration to blind people: phase advances and entrainment.

The purpose of this study was to test the phase-shifting and entraining effects of melatonin in human subjects. Five totally blind men were found in a previous study to have free-running endogenous melatonin rhythms. Their rhythms were remarkably stable, so that any deviation from the predicted phase was readily detectable. After determination of their free-running period and phase, they were given exogenous melatonin (5 mg) at bedtime (2200 hr) for 3 weeks, in a double-blind, placebo-controlled trial. The effects on the endogenous melatonin rhythm were assessed at intervals ranging from several days to 2 weeks. Exogenous administration of melatonin phase-advanced their endogenous melatonin rhythms. In three of the subjects, cortisol was shown to be phase-shifted in tandem with the melatonin rhythm. A sixth subject [one of the coauthors (JS)] was previously found to have free-running cortisol and temperature rhythms and was plagued by recurrent insomnia and daytime sleepiness. He had tried unsuccessfully to entrain his rhythms for over 10 years. After he took melatonin (7 mg at 2100 hr), his insomnia and sleepiness resolved. Determination of his endogenous melatonin rhythm after about a year of treatment demonstrated endogenous rhythms that appeared normally entrained. The treatment of blind people with free-running rhythms has many advantages for demonstrating chronobiological effects of hormones or drugs.

Adult↗
PubMed1990

Morning vs evening light treatment for winter depression. Evidence that the therapeutic effects of light are mediated by circadian phase shifts.

Bright light exposure has been found to alleviate the symptoms of recurrent winter depression in many patients. The mechanism of light therapy may involve shifts in the timing (phase) of circadian rhythms. In this study, morning light exposure (which shifts rhythms earlier) was compared with evening light exposure (which shifts rhythms later) in a double-blind, crossover design. The onset of melatonin secretion in the evening was measured under dim light conditions as a marker for circadian timing (phase) before and after each treatment. Eight patients with winter depression and five control subjects were studied. Morning light was found to be significantly better than evening light in reducing depressive symptoms. At baseline, there was a trend for the onset of melatonin production to be later in the patients than in the controls. Morning light shifted the melatonin onset significantly earlier in the patients but not the controls. Our findings suggest that patients with winter depression have circadian rhythms that are abnormally delayed and that bright light therapy benefits winter depression by providing a corrective advance.

Adult↗
PubMed1990

Pineal-adrenal interactions: the effect of acute pharmacological blockade of nocturnal melatonin secretion.

The pineal gland is a complex neuroendocrine organ which is under photoneuroendocrine control. Previous studies in animals and humans have suggested reciprocal variations in pineal melatonin biosynthesis and adrenal glucocorticoid output; it remains unclear, however, whether a causal relationship exists between these two systems. To address this question, we examined the overnight secretory activity of the hypothalamic-pituitary-adrenal (HPA) axis in conjunction with acute pharmacological suppression of pineal melatonin biosynthesis in 11 healthy volunteers. Results of the current study are consistent with the hypothesis that melatonin does not function as a tonic inhibitor of the HPA axis on an acute basis.

Adult↗
PubMed1990

Light suppression of melatonin in the squirrel monkey (Saimiri sciureus).

This study examined plasma melatonin levels and the suppressant effect of light on melatonin production in the squirrel monkey. Monkeys were maintained on a 12:12 light-dark cycle (LD 12:12) with lights on from 07:00 to 19:00. Plasma levels of melatonin were determined by gas chromatography negative chemical ionization mass spectrometry. Melatonin levels at 00:00 (99.5 +/- 18.9 pg/ml) were significantly higher than at 02:00 (57.21 +/- 7.7 pg/ml; Student's t = 2.859; P less than or equal to 0.021). Baseline values at 02:00 were compared with levels at the same time of day after exposure to 2 hours of 200 lux of light (30.6 +/- 13.1 pg/ml), which caused an average suppression of 54.8% in melatonin levels. One animal did not show light suppression. Results indicated that the squirrel monkey suppressant response to light, as well as baseline values of melatonin, varied between animals.

Animals↗
PubMed1989

Bright morning light advances the human circadian system without affecting NREM sleep homeostasis.

Eight male subjects were exposed to either bright light or dim light between 0600 and 0900 h for 3 consecutive days each. Relative to the dim light condition, the bright light treatment advanced the evening rise in plasma melatonin and the time of sleep termination (sleep onset was held constant) for an average approximately 1 h. The magnitude of the advance of the plasma melatonin rise was dependent on its phase in dim light. The reduction in sleep duration was at the expense of rapid-eye-movement (REM) sleep. Spectral analysis of the sleep electroencephalogram (EEG) revealed that the advance of the circadian pacemaker did not affect EEG power densities between 0.25 and 15.0 Hz during either non-REM or REM sleep. The data show that shifting the human circadian pacemaker by 1 h does not affect non-REM sleep homeostasis. These findings are in accordance with the predictions of the two-process model of sleep regulation.

Adult↗
PubMed1989

Ontogenesis of pineal thyroxine 5'-deiodinase activity and plasma melatonin concentration in the rat.

Rat pineal thyroxine 5'-deiodinase (5'-D) activity was detectable by 5 days after birth. Nyctohemeral differences became significant by 10 days of age and gradually reached adult magnitude at 1-2 months, primarily due to a progressive increase in nocturnal enzyme activity. A nyctohemeral difference in N-acetyltransferase (NAT) activity was observed by 5 days postnatally and the maturation of NAT rhythmicity was characterized by both a decrease in diurnal and an increase in nocturnal enzyme activity. The maturation of 5'-D rhythmicity was slower than that of NAT. Isoproterenol stimulated 5'-D activity in 5-day-old rats in which there was no spontaneous nyctohemeral 5'-D rhythm, suggesting that the appearance of rhythmicity in pineal 5'-D may depend on the development of pineal innervation. Melatonin was detectable in plasma by 5 days postnatally and reached adult levels at 21 days. A nyctohemeral difference in plasma melatonin concentration existed from day 5 with the highest value at midnight. The difference between noon and midnight increased approximately 10-fold to the adult amplitude by 15 days of age. There was a transient rise of both diurnal and nocturnal plasma melatonin concentration which peaked at 10 days before dropping severalfold to the adult level for both noon and midnight values by 21 days. Since the rhythms of pineal NAT activity and of plasma melatonin concentration are established before that of pineal 5'-D, it is unlikely that the rhythm of melatonin secretion is initiated by a prior maturation of the pineal 5'-D rhythm.

Acetyltransferases↗
PubMed1989

Increase in plasma melatonin, beta-endorphin, and cortisol after a 28.5-mile mountain race: relationship to performance and lack of effect of naltrexone.

Strenuous exercise increases plasma melatonin, cortisol, and beta-endorphin concentrations. Furthermore, a relationship between endogenous opioids and melatonin has been proposed. We measured plasma melatonin, cortisol, and beta-endorphin in 46 subjects before and after a 28.5-mile high altitude race. Thirteen of the subjects received the orally active opioid antagonist naltrexone immediately before the race. The mean plasma melatonin, cortisol, and beta-endorphin levels were higher after the race than before it; the melatonin results were confirmed by gas chromatography-mass spectrometry assay of 12 subjects. Naltrexone had no effect on the increase in any of the three hormones. The run-induced increases in plasma melatonin, beta-endorphin, and cortisol were negatively correlated with finishing time, but only the plasma beta-endorphin and cortisol rises correlated with each other. We conclude that prolonged exercise in trained athletes can increase plasma melatonin and that this rise is not due to the concomitant opioid release.

Adult↗
PubMed1989

Entrainment of a free-running human with bright light?

The case of a 40-year-old sighted woman with free-running sleep-wake and melatonin rhythms is presented. The subject was studied for 102 days. During the pre-treatment period, both the sleep-wake and melatonin rhythms had a period of 25.1 hr, similar to the average period of humans living in temporal isolation. Treatment consisted of bright artificial light exposure (2500 lx Vita-Lite) for 2 hr each day upon awakening. Clock time of light exposure was held constant for 6 days and then slowly advanced until the subject was arising at her desired time of day. The subject continued the light treatment at home and was able to live on a 24-hr day for the 30-day follow-up study. While other factors may be operating in this situation, it is possible that the light treatment caused the stabilization of the free-running rhythms, advancement to a normal phase and entrainment to the 24-hr day. We suspect that the tendency to free-run was related to sleep onsets that were abnormally delayed relative to the circadian phase response curve for light. By scheduling a 2-hr pulse of bright light each morning, this tendency to delay would be counteracted by light-induced advances, resulting in normal entrainment.

Adult↗
PubMed1989

The dim light melatonin onset as a marker for circadian phase position.

Masking is known to affect a variety of circadian rhythms, making it difficult to use them as reliable markers of circadian phase position. Melatonin may be unique in that it appears to be masked only by (bright) light. Sleep and activity do not appear to influence the melatonin rhythm. By measuring the onset of melatonin production, a clearly demarcated event, we can reliably assess circadian phase position, provided blood is sampled under dim light (the dim light melatonin onset, or DLMO). The DLMO has been useful in assessing the phase-shifting properties of bright light and in phase typing patients with chronobiologic disorders, such as winter depression.

Animals↗
PubMed1988

Dose-response relationship between light irradiance and the suppression of plasma melatonin in human volunteers.

This study tested the capacity of different irradiances of monochromatic light to reduce plasma melatonin in normal humans. Six healthy male volunteers, 24-34 years old, were exposed to 0.01, 0.3, 1.6, 5, or 13 microW/cm2 of 509 nm monochromatic light for 1 h during the night on separate occasions. Light irradiance depressed plasma melatonin in a dose-response pattern. The data indicate that the mean threshold irradiance for suppressing melatonin is between 1.6 and 5 microW/cm2. Individual variations in threshold responses to monochromatic light were observed among the volunteers.

Adult↗