Biomedical subjects

O M Buxton

Publications and source records attributed to O M Buxton.

10 recordsLinked to original sources

PubMed2002

Circadian variation in Cushing's disease and pseudo-Cushing states by analysis of F and ACTH pulsatility.

Distinguishing pituitary-dependent Cushing's disease from pseudo-Cushing's states can present a diagnostic challenge. Although many studies potentially discriminate between the 2, only the dexamethasone-suppressed corticotropin-releasing hormone (CRF) stimulation test at 15 minutes is 100% sensitive or specific. We measured baseline profiles of F and ACTH in 31 Cushing's disease patients, 11 with pseudo-Cushing's and 17 controls. Venous blood was collected at 30 minute intervals for 24-h. Subjects also had CRF stimulation tests and 2.0 mg/day dexamethasone suppression tests. F and ACTH profiles were analyzed for circadian rhythmicity, variability, and pulsatility. Relative circadian amplitude was decreased in Cushing's disease compared to both pseudo-Cushing's and normal states. Relative pulse amplitude was reduced in Cushing's disease. Because of this dampening of circadian and pulsatile variations, the overall variability of F and ACTH levels around their mean levels as quantified by the intra-series coefficient of variation (CV), was also decreased in Cushing's disease compared to pseudo-Cushing's and normal states. A F 24-h CV<40% was able to distinguish Cushing's disease from pseudo-Cushing's with 100% sensitivity (95% confidence interval (CI), 88-100%) and specificity (CI, 71-100%). An ACTH CV<40% had 97% sensitivity (CI, 83-100%) and 100% specificity (CI, 71-100%). An overnight 8-h F CV <40% also distinguished Cushing's disease from pseudo-Cushing's with 100% sensitivity (CI, 88-100%) and specificity (CI, 71-100%). These data show that a simple index of total temporal variability (the intra-series CV) derived from the analysis of basal F profiles, provides a useful method to distinguish Cushing's disease from pseudo-Cushing's. A F or ACTH CV <40% discriminates Cushing's disease from pseudo-Cushing's and reflects reduced circadian and pulsatile variations.

Adolescent↗

PubMed2000

A benzodiazepine hypnotic facilitates adaptation of circadian rhythms and sleep-wake homeostasis to an eight hour delay shift simulating westward jet lag.

STUDY OBJECTIVES: To determine whether appropriately timed administration of a short-acting benzodiazepine hypnotic, which has proven effective in an animal model of jet lag, also facilitates adaptation of circadian rhythmicity and sleep-wake homeostasis in a human model of jet lag. DESIGN: Subjects participated in two double-blind, placebo-controlled studies of adaptation to an 8-hr delay shift of sleep-wake and dark-light cycles simulating westward travel. Each 9-day laboratory study began with a 3-day habituation period followed by a 24-hr study to obtain basal hormonal and sleep profiles (23:00-07:00). Subjects were then kept awake until 07:00 the next day and slept in darkness 07:00-15:00 for the next five 24-hr spans post-shift. SETTING: N/A. PARTICIPANTS: 6 normal, healthy men 24-31 years of age. INTERVENTIONS: Oral Triazolam (0.5 mg) or placebo given at 04:00 before the first shifted sleep/dark period (3 hours before bedtime) and at 07:00 (at bedtime) on days 2-5 post-shift. MEASUREMENTS AND RESULTS: Sleep recordings and 24-hr cortisol and growth hormone profiles were obtained at baseline and on the first, third, and fifth days post-shift. Global measures of treatment efficacy were calculated for multiple endpoints representing circadian rhythmicity and sleep-wake homeostasis. With placebo, the shift induced disturbances of sleep and hormonal secretion, and a gradual re-entrainment of circadian rhythmicity. Triazolam significantly facilitated adaptation by accelerating re-entrainment of circadian rhythms (chronobiotic effect) and normalizing markers of sleep/wake homeostasis (hypnotic effect). CONCLUSIONS: Appropriately timed administration of a benzodiazepine hypnotic appears to facilitate the adaptation of both circadian rhythmicity and sleep-wake homeostasis to a shifted dark/sleep cycle. Compounds with combined chronobiotic/hypnotic properties may be useful in conditions of jet lag or night work.

Adaptation, Physiological↗

PubMed2000

Twenty-four-hour profiles of serum leptin in siberian and golden hamsters: photoperiodic and diurnal variations.

Serum leptin concentrations were obtained from male Siberian hamsters (Phodopus sungorus) and golden hamsters (a.k.a. Syrian, Mesocricetus auratus) housed on long [light:dark (LD) 16:8] and short (LD 6:18) photoperiods for 10-11 weeks. Blood samples were collected at 45-min intervals for 24 h from individual animals using an in-dwelling atrial catheter. In Siberian hamsters, exposure to short photoperiods as compared to long photoperiods reduced body weight (32.5 +/- 1.5 vs 47.7 +/- 1.1 g) and leptin (24-h mean: 5.3 +/- 0.4 ng/ml vs 18.6 +/- 2.1 ng/ml). Although photoperiod influenced the temporal distribution of leptin in golden hamsters, the main effect of photoperiod on leptin levels in golden hamsters did not reach significance (24-h mean: 7.1 +/- 1.0 ng/ml vs 5.1 +/- 0.8 ng/ml.). Body weights of golden hamsters did not vary significantly following exposure to short photoperiod for 11 weeks (178.3 +/- 3.6 g in LD 6:18 vs 177.8 +/- 7.3 g in LD 16:8). There was no nocturnal increase in serum leptin in either species. Marked interindividual differences were apparent in individual leptin profiles. Periodogram analysis revealed that only a few animals exhibited 24-h periodicities; the presence of a significant 24-h periodicity was more common in hamsters exposed to short days. Photoperiod-associated differences in the 24-hour profile of leptin secretion may be the result of photoperiod-associated changes in feeding behavior or metabolism. A full understanding of the regulation of leptin secretion in multiple time domains may enhance our understanding of the function of leptin.

Animals↗

PubMed2000

Locomotor response to an open field during C57BL/6J active and inactive phases: differences dependent on conditions of illumination.

Time of day has proven to be a source of variability in diverse behavioral measures. Knowledge of the pattern of this temporal effect as well as its origin (exogenous or endogenous) is essential for a precise description of any behavior. This study analyzed the effect of the external light-dark cycle and the internal rest-activity rhythm on the response of C57BL/6J mice to a novel environment. In a first experiment, animals maintained in a 12:12-h light-dark cycle were tested in an open field at six different times of day. A diurnal rhythm of ambulation in the open field was observed with greater levels of activity exhibited by those groups tested at night. Long-term and short-term behavioral habituation to spatial novelty were also affected by phase of the light-dark cycle. A second experiment was designed to control for any direct effect of the light-dark cycle by keeping the animals in dim green light where entrainment was maintained by a skeleton photoperiod (two 15-min bright-light pulses separated by 12 hours of green, dim light). This second group of animals was tested at two different circadian phases under the same conditions of illumination. One group was tested during the subjective night and another group during the subjective day, i.e., 2 or 14 h after the onset of the active phase, as assessed by wheel-running behavior. No effect of circadian phase on ambulation or habituation of this response to the open field was observed in these animals. Taken together, these results suggest that spatial novelty is equally arousing regardless of circadian phase and that the conditions of illumination can dramatically alter the response to a novel environment.

Animals↗

PubMed2000

Daytime naps in darkness phase shift the human circadian rhythms of melatonin and thyrotropin secretion.

To systematically determine the effects of daytime exposure to sleep in darkness on human circadian phase, four groups of subjects participated in 4-day studies involving either no nap (control), a morning nap (0900-1500), an afternoon nap (1400-2000), or an evening nap (1900-0100) in darkness. Except during the scheduled sleep/dark periods, subjects remained awake under constant conditions, i.e., constant dim light exposure (36 lx), recumbence, and caloric intake. Blood samples were collected at 20-min intervals for 64 h to determine the onsets of nocturnal melatonin and thyrotropin secretion as markers of circadian phase before and after stimulus exposure. Sleep was polygraphically recorded. Exposure to sleep and darkness in the morning resulted in phase delays, whereas exposure in the evening resulted in phase advances relative to controls. Afternoon naps did not change circadian phase. These findings indicate that human circadian phase is dependent on the timing of darkness and/or sleep exposure and that strategies to treat circadian misalignment should consider not only the timing and intensity of light, but also the timing of darkness and/or sleep.

Adult↗

PubMed1998

Effects of aging on sleep in the golden hamster.

The golden hamster (Mesocricetus auratus) has been a model organism for the study of circadian rhythmicity and, in particular, the effects of age on the circadian system. Surprisingly, nothing is known about the effects of advanced age on sleep in this species. As a first step in determining the effects of aging on sleep in the golden hamster, we recorded sleep for 24 hours in 12 young (3 months) and 18 old (17-18 months) golden hamsters entrained to a 14:10 light:dark (LD) cycle. Aged hamsters exhibited small but significant increases in overall NREM sleep time, primarily due to an increase in time the old animals spent in the NREM sleep state during the dark period relative to the young hamsters. There were no significant differences in REM sleep, median sleep episode length, or the number of arousals. The most striking differences between the sleep of young and old hamsters was in NREM delta (0.5-4 Hz) power per epoch. Old hamsters showed approximately 27% less (p=0.0004) delta power per NREM epoch than young hamsters. It is possible that increased NREM sleep time in the old hamsters may be a failed attempt to maintain cumulative delta power; ie, old hamsters may have more NREM sleep in order to make up for the lower intensity of their sleep. This decline in delta power with age parallels earlier findings in cats and humans, although has it not been previously reported in rodents.

Age Factors↗

PubMed1998

Effects of exercise on neuroendocrine secretions and glucose regulation at different times of day.

To study the effects of time of day on neuroendocrine and metabolic responses to exercise, body temperature, plasma glucose, insulin secretion rates (ISR), and plasma cortisol, growth hormone (GH) and thyrotropin (TSH) were measured in young men, both at bed rest and during a 3-h exercise period (40-60% maximal O2 uptake). Exercise was performed at three times of day characterized by marked differences in cortisol levels, i.e., early morning (n = 5), afternoon (n = 8), and around midnight (n = 9). The subjects were kept awake and fasted, but they received a constant glucose infusion to avoid hypoglycemia. Exercise-induced elevations of temperature were higher in the early morning than at other times of day. The exercise-induced glucose decrease was approximately 50% greater around midnight, when cortisol was minimal and not stimulated by exercise, than in the afternoon or early morning (P < 0.05). This effect of time of day appeared unrelated to decreases in ISR or increases in temperature and GH. Robust TSH increases occurred in all exercise periods and were maximal at night. The results demonstrate the existence of circadian variations in neuroendocrine and metabolic responses to exercise.

Adult↗

PubMed1997

Synchronizing circadian rhythms in early infancy.

Entrainment to the 24-hour light-dark cycle is of adaptive significance to mammals. Human infants are no exception, but some postnatal care habits prevalent in developed countries can interfere with the physiological mechanisms underlying circadian synchronization. We describe the physiological mechanisms of entrainment to the light-dark cycle in fetuses and newborns, and some common parental care behaviors which subject the developing circadian system of the newborn to conflicting temporal cues. Improvements in parental care are proposed which may improve the circadian synchronization of newborns, and their parents or caregivers.

Animals↗

PubMed1997

Roles of intensity and duration of nocturnal exercise in causing phase delays of human circadian rhythms.

To determine the roles of intensity and duration of nocturnal physical activity in causing rapid phase shifts of human circadian rhythms, eight healthy men were studied three times under constant conditions with no exercise, a 3-h bout of moderate-intensity exercise, or a 1-h bout of high-intensity exercise. Exercise stimulus was centered at 0100. Circadian phase was estimated from the onsets of the nocturnal elevation of plasma thyrotropin (TSH) and melatonin. Mean phase shifts of TSH onsets were -18 +/- 8 (baseline), -78 +/- 10 (low-intensity exercise, P < 0.01), and -95 +/- 19 min (high-intensity exercise, P < 0.01). Mean phase delays of melatonin onsets were -23 +/- 10 (baseline), -63 +/- 8 (low-intensity exercise, P < 0.04), and -55 +/- 15 min (high-intensity exercise, P < 0.12). Taken together with our previous findings, this study indicates that nocturnal physical activity may phase delay human circadian rhythms and demonstrates that phase-shifting effects may be determined with exercise durations and intensities compatible with the demands of a real-life setting.

Adult↗

PubMed1997

Acute and delayed effects of exercise on human melatonin secretion.

Accumulating evidence suggests that exercise may have both rapid and delayed effects on human melatonin secretion. Indeed, exercise may acutely (i.e., within minutes) alter melatonin levels and result in a shift of the onset of nocturnal melatonin 12 to 24 h later. The presence and nature of both acute and delayed effects appear to be dependent on the timing of exercise. The presence of a detectable acute effect also depends on the duration, intensity, and type of exercise. Late evening exercise during the rising phase of melatonin secretion may blunt melatonin levels. High-intensity exercise during the nighttime period, when melatonin levels already are elevated, consistently results in a further (nearly 50%) elevation of melatonin levels. No effect of low-intensity exercise performed at the same circadian phase could be detected. Irrespective of intensity, exercise near the offset of melatonin secretion or during the daytime has no consistent acute effect on melatonin secretion. Nighttime exercise, whether of moderate or high intensity, results in phase delays of the melatonin onset on the next evening. In support of the concept that a shift of the melatonin onset on the day after nighttime exercise represents a shift of intrinsic circadian timing is the observation that similar phase shifts (in both direction and magnitude) may be observed simultaneously for the onset of the circadian elevation of thyrotropin secretion. The observation of exercise-induced phase shifts of the onset of melatonin secretion is, therefore, interpreted as evidence that, in humans as in rodents, increased physical activity during the habitual rest period is capable of altering circadian clock function.

Exercise↗