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Biomedical subjects

R L Sack

Publications and source records attributed to R L Sack.

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↗
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↗
PubMed1987

Antidepressant and circadian phase-shifting effects of light.

Bright light can suppress nighttime melatonin production in humans, but ordinary indoor light does not have this effect. This finding suggested that bright light may have other chronobiologic effects in humans as well. Eight patients who regularly became depressed in the winter (as day length shortens) significantly improved after 1 week of exposure to bright light in the morning (but not after 1 week of bright light in the evening). The antidepressant response to morning light was accompanied by an advance (shift to an earlier time) in the onset of nighttime melatonin production. These results suggest that timing may be critical for the antidepressant effects of bright light.

Circadian Rhythm↗
PubMed1987

Civil commitment by conservatorship: the workings of California's law.

This article summarizes the conservatorship provisions of the California Civil Commitment Statute, the Lanterman-Petris-Short (LPS) Act and reviews the major findings from previous studies. By studying the hospital records of eighty-five gravely disabled patients affected by LPS, the authors address issues raised by these reports. The results indicate that the law's provisions work unevenly. Patients with acute and current disability received conservatorships more frequently than those who had been disabled in the past. There is some evidence that the process is used to confine threatening patients and does not function equally well for all diagnostic groups.

Activities of Daily Living↗
PubMed1986

Flurbiprofen in the treatment of acute gout. A comparison with indomethacin.

The relative efficacy and safety of flurbiprofen (Ansaid, Upjohn) and indomethacin were compared in 29 patients with monoarticular gouty arthritis of less than 48 hours' duration. A loading dose of 400 mg of flurbiprofen or 200 mg of indomethacin was administered for 24 hours, followed by 200 mg of flurbiprofen per day or 100 mg of indomethacin per day for a maximum of five days. Based on global assessment of improvement, at least 50 percent of patients in both treatment groups showed improvement within 24 hours. There were statistically significant improvements in pain, swelling, erythema, and skin temperature in both groups of patients within 48 hours of treatment. By 72 hours, the proportion of patients with improvement in the flurbiprofen group was equal to or greater than the proportion in the indomethacin group for all clinical efficacy parameters. At the end of treatment, eight of 15 patients in the indomethacin group and five of 14 patients in the flurbiprofen group were asymptomatic. There were no statistically significant differences between indomethacin and flurbiprofen in the percentage of asymptomatic patients at the end of treatment. Side effects were mild in both groups. No clinically significant between-treatment differences were noted in vital signs or in the results of laboratory assays.

Acute Disease↗