Bright light induction of strong (type 0) resetting of the human circadian pacemaker.

The response of the human circadian pacemaker to light was measured in 45 resetting trials. Each trial consisted of an initial endogenous circadian phase assessment, a three-cycle stimulus which included 5 hours of bright light per cycle, and a final phase assessment. The stimulus induced strong (type 0) resetting, with responses highly dependent on the initial circadian phase of light exposure. The magnitude and direction of the phase shifts were modulated by the timing of exposure to ordinary room light, previously thought to be undetectable by the human pacemaker. The data indicate that the sensitivity of the human circadian pacemaker to light is far greater than previously recognized and have important implications for the therapeutic use of light in the management of disorders of circadian regulation.

Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle.

Human circadian rhythms were once thought to be insensitive to light, with synchronization to the 24-hour day accomplished either through social contacts or the sleep-wake schedule. Yet the demonstration of an intensity-dependent neuroendocrine response to bright light has led to renewed consideration of light as a possible synchronizer of the human circadian pacemaker. In a laboratory study, the output of the circadian pacemaker of an elderly woman was monitored before and after exposure to 4 hours of bright light for seven consecutive evenings, and before and after a control study in ordinary room light while her sleep-wake schedule and social contacts remained unchanged. The exposure to bright light in the evening induced a 6-hour delay shift of her circadian pacemaker, as indicated by recordings of body temperature and cortisol secretion. The unexpected magnitude, rapidity, and stability of the shift challenge existing concepts regarding circadian phase-resetting capacity in man and suggest that exposure to bright light can indeed reset the human circadian pacemaker, which controls daily variations in physiologic, behavioral, and cognitive function.

Stability, precision, and near-24-hour period of the human circadian pacemaker.

Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.

[Delayed perforation of the cecum and sigmoid colon after blunt abdominal trauma in a patient with multiple injuries]. / Perforación diferida de ciego y sigma tras traumatismo abdominal cerrado en paciente politraumatizado.

Blunt abdominal trauma can damage the intestinal vasculature and may occasionally lead to delayed intestinal perforation, associated with a combined rate of morbidity and mortality of 25%. The diagnosis of such complications is hindered by sedation in critical patients, however, and morbimortality in this population is therefore higher. We report the case of a man with multiple injuries admitted to the intensive care unit, where delayed perforations of the sigmoid colon and cecum were diagnosed. The management of blunt abdominal trauma is reviewed and the possible causes, diagnostic approaches, and treatment options for colon injuries are discussed.

Timing of REM sleep is coupled to the circadian rhythm of body temperature in man.

Ten male subjects were studied for a total of 306 days on self-selected schedules. Four of them developed bedrest-activity cycle period lengths very different from 24 hr (mean = 36.8 hr) despite the persistence of near-24-hr oscillations in other physiologic functions, including that of body temperature (mean = 24.6 hr). The percentage of sleep time spent in REM sleep varied significantly with the phase of that near-24-hr body temperature cycle. The peak in REM sleep propensity (RSP) occurred on the rising slope of the average body temperature curve, coincident with the phase of peak sleep tendency. This was associated with a significantly increased REM episode duration and shortened REM latency (including sleep-onset REM episodes), but without a significant change in the REM-NREM cycle length. We conclude that there is an endogenous circadian rhythm of REM sleep propensity which is closely coupled to the body temperature rhythm and is capable of free-running with a period different from both 24 hr and the average period of the sleep-wake cycle.

Timing of REM and stages 3 + 4 sleep during temporal isolation in man.

During nonentrained sleep--wake conditions in man, healthy adult subjects spontaneously develop "long" biological days (greater than 35 hr) in addition to the normal, approximately 25 hr day. The ratio of sleep to total time remains constant (approximately 0.30), with long sleep episodes occurring approximately 180 degrees out of phase with the short sleep episodes. The timing and amount of REM sleep advance to an earlier time within the sleep episode during free-running, whereas stage 3 + 4 sleep is related to the initiation and course of the sleep process itself. The REM--NREM cycle length does not change, comparing entrained and nonentrained conditions. The study of the chronophysiology of humans under nonentrained conditions may serve as a model of the chronopathology of sleep--wake changes which occur in sleep disorders associated with depression, narcolepsy--cataplexy, sleep--wake dyssomnias, delayed sleep phase insomnia, and aging.

[Relation between clinical symptoms and the results of a computerized dynamic posturography]. / Asociación entre síntomas clínicos y resultados de la posturografía computarizada dinámica.

The computerized dynamic posturography (CDP) is a quantitative method for the evaluation of balance function under different conditions that simulates the ones found in normal life. Its applications are centered in the diagnosis and rehabilitation of balance dysfunction. We report a descriptive study on 96 patients with balance disorders who underwent a CDP, stablishing a relation between their main symptoms and the results in the test. A high percentage of patients with symptoms that suggested peripheral vestibular pathology did not present alterations at this level by means of the CDP. However a considerable number of patients who referred symptoms classically related to a non vestibular origin did show an alteration at this level.

[Allergic fungal sinusitis]. / Sinusitis fúngica alérgica.

Allergic fungal sinusitis is a recently described clinical entity that has gained increased attention as a cause of chronic sinusitis. Consist in a benign noninvasive sinus disease related to a hypersensitivity reaction to fungal antigens. It should be suspected in any atopic patient with refractory nasal polyps. Computed tomography (CT) findings are characteristics, but not diagnostic. Diagnosis requires show allergic mucin in the histopathologic examination and hiphae in special fungal stains. The suitable treatment includes the allergic mucin removal and sinus aeration accomplished endoscopically, perioperative systemic steroids and immunotherapy with fungal antigens. We present a case of this kind of chronic sinusitis describing the characteristic histopathologic and radiologic findings, the pathogenic theories and recent advances in immunotherapy.

[Midfacial necrosis secondary to cocaine-abuse]. / Necrosis mediofacial secundaria al abuso de cocaína.

Midfacial necrosis due to the abuse of inhaled cocaine is a new entity that is included in the differential diagnosis of the midline destructive diseases such as Wegener's granulomatosis, polymorphic reticulosis, nasal lymphoma, infections and the idiopathic midline destructive disease. We report the case of a forty-year-old male who presented necrosis of the nasosinusal tract and optic neuropathy as complications due to the abuse of inhaled cocaine for more than twenty years and a discussion about the differential diagnosis.

Effects on subjective and objective alertness and sleep in response to evening light exposure in older subjects.

Evening bright light exposure is reported to ameliorate daytime sleepiness and age-related sleep complaints, and also delays the timing of circadian rhythms. We tested whether evening light exposure given to older adults with sleep-wake complaints would delay the timing of their circadian rhythms with respect to their sleep timing, thereby reducing evening sleepiness and improving subsequent sleep quality. We examined the impact of evening light exposure from two different light sources on subjective alertness, EEG activity during wakefulness, and sleep stages. Ten healthy older adults with sleep complaints (mean age=63.3 years; 6F) participated in a 13-day study. After three baseline days, circadian phase was assessed. On the evening of days 5-8 the subjects were exposed for 2h to either polychromatic blue-enriched white light or standard white fluorescent light, and on the following day circadian phase was re-assessed. Subjects were allowed to leave the laboratory during all but the two days when the circadian phase assessment took place. Evening assessments of subjective alertness, and wake and sleep EEG data were analyzed. Subjective alertness and wake EEG activity in the alpha range (9.75-11.25 Hz) were significantly higher during light exposures when compared to the pre-light exposure evening (p<0.05). The light exposures produced circadian phase shifts and significantly prolonged latency to rapid eye-movement (REM) sleep for both light groups (p<0.05). The increase in wake EEG alpha activity during the light exposures was negatively correlated with REM sleep duration (p<0.05). Evening light exposure could benefit older adults with early evening sleepiness, without negatively impacting the subsequent sleep episode.

Exposure to bright light and darkness to treat physiologic maladaptation to night work.

Working at night results in a misalignment between the sleep-wake cycle and the output of the hypothalamic pacemaker that regulates the circadian rhythms of certain physiologic and behavioral variables. We evaluated whether such physiologic maladaptation to nighttime work could be prevented effectively by a treatment regimen of exposure to bright light during the night and darkness during the day. We assessed the functioning of the circadian pacemaker in five control and five treatment studies in order to assess the extent of adaptation in eight normal young men to a week of night work. In the control studies, on the sixth consecutive night of sedentary work in ordinary light (approximately 150 lux), the mean (+/- SEM) nadir of the endogenous temperature cycle continued to occur during the night (at 3:31 +/- 0:56 hours), indicating a lack of circadian adaptation to the nighttime work schedule. In contrast, the subjects in the treatment studies were exposed to bright light (7000 to 12,000 lux) at night and to nearly complete darkness during the day, and the temperature nadir shifted after four days of treatment to a significantly later, midafternoon hour (14:53 +/- 0:32; P less than 0.0001), indicating a successful circadian adaptation to daytime sleep and nighttime work. There were concomitant shifts in the 24-hour patterns of plasma cortisol concentration, urinary excretion rate, subjective assessment of alertness, and cognitive performance in the treatment studies. These shifts resulted in a significant improvement in both alertness and cognitive performance in the treatment group during the night-shift hours. We conclude that maladaptation of the human circadian system to night work, with its associated decline in alertness, performance, and quality of daytime sleep, can be treated effectively with scheduled exposure to bright light at night and darkness during the day.

Short-term memory, alertness and performance: a reappraisal of their relationship to body temperature.

Previous studies have led to the beliefs: (1) that short-term memory is best during the night when the body temperature is at its nadir, and (2) that the circadian rhythms of short-term memory and subjective alertness are driven by oscillators independent from each other and from the body temperature cycle. Unfortunately, these conclusions, which would have major implications for understanding the organization of the human circadian timing system, are largely based on field and laboratory studies, which in many cases sampled data infrequently and/or limited data collection to normal waking hours. In order to investigate these points further, we have monitored behavioural variables in two different protocols under controlled laboratory conditions: (1) during a period of 36-60 h of sustained wakefulness; and (2) during forced desynchrony between the body temperature and sleep/wake cycles, allowing testing of non-sleep-deprived subjects at all circadian phases. Contrary to earlier findings, we report here that the circadian rhythm of short-term memory varies in parallel with the circadian rhythms of subjective alertness, calculation performance, and core body temperature under both these experimental conditions. These results challenge the notion that short-term memory is inversely linked to the body temperature cycle and suggest that the human circadian pacemaker, which drives the body temperature cycle, is the primary determinant of endogenous circadian variations in subjective alertness and calculation performance as well as in the immediate recall of meaningful material.

Variation of electroencephalographic activity during non-rapid eye movement and rapid eye movement sleep with phase of circadian melatonin rhythm in humans.

1. The circadian pacemaker regulates the timing, structure and consolidation of human sleep. The extent to which this pacemaker affects electroencephalographic (EEG) activity during sleep remains unclear. 2. To investigate this, a total of 1.22 million power spectra were computed from EEGs recorded in seven men (total, 146 sleep episodes; 9 h 20 min each) who participated in a one-month-long protocol in which the sleep-wake cycle was desynchronized from the rhythm of plasma melatonin, which is driven by the circadian pacemaker. 3. In rapid eye movement (REM) sleep a small circadian variation in EEG activity was observed. The nadir of the circadian rhythm of alpha activity (8.25-10.5 Hz) coincided with the end of the interval during which plasma melatonin values were high, i.e. close to the crest of the REM sleep rhythm. 4. In non-REM sleep, variation in EEG activity between 0.25 and 11.5 Hz was primarily dependent on prior sleep time and only slightly affected by circadian phase, such that the lowest values coincided with the phase of melatonin secretion. 5. In the frequency range of sleep spindles, high-amplitude circadian rhythms with opposite phase positions relative to the melatonin rhythm were observed. Low-frequency sleep spindle activity (12.25-13.0 Hz) reached its crest and high-frequency sleep spindle activity (14.25-15.5 Hz) reached its nadir when sleep coincided with the phase of melatonin secretion. 6. These data indicate that the circadian pacemaker induces changes in EEG activity during REM and non-REM sleep. The changes in non-REM sleep EEG spectra are dissimilar from the spectral changes induced by sleep deprivation and exhibit a close temporal association with the melatonin rhythm and the endogenous circadian phase of sleep consolidation.

Association of sleep-wake habits in older people with changes in output of circadian pacemaker.

Many elderly people complain of disturbed sleep patterns but there is not evidence that the need to sleep decreases with age; it seems rather that the timing and consolidation of sleep change. We tried to find out whether there is a concurrent change in the output of the circadian pacemaker with age. The phase and amplitude of the pacemaker's output were assessed by continuous measurement of the core body temperature during 40 h of sustained wakefulness under constant behavioural and environmental conditions. 27 young men (18-31 years) were compared with 21 older people (65-85 years; 11 men, 10 women); all were healthy and without sleep complaints. The mean amplitude of the endogenous circadian temperature oscillation (ECA) was 40% greater in young men than in the older group. Older men had a lower mean temperature ECA than older women. The minimum of the endogenous phase of the circadian temperature oscillation (ECP) occurred 1 h 52 min earlier in the older than in the young group. Customary bedtimes and waketimes were also earlier in the older group, as was their daily alertness peak. There was a close correlation between habitual waketime and temperature ECP in young men, which may lose precision with age, especially among women. These findings provide evidence for systematic age-related changes in the output of the human circadian pacemaker. We suggest that these changes may underlie the common complaints of sleep disturbance among elderly people. These changes could reflect the observed age-related deterioration of the hypothalamic nuclei that drive mammalian circadian rhythms.

Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights.

Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.