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Plasma LH, FSH and prolactin secretory patterns were derived from the measurement of 20-min interval plasma samples obtained during a complete 24-h period in a patient with persistent postpartum amenorrhe a and galactorrhea (Chiari-Frommel syndrome), before and after clomiphene citrate therapy. During nocturnal sleep, polygraphic monitoring was carried out to precisely identify sleep onset, specific sleep stages and waking periods. During the evening and nighttime hours, LH and FSH concentrations were markedly reduced, compared to the daytime patterns both before and after clomiphene therapy. A sleep-associated rise of prolactin concentration was present, similar to the pattern found in normal subjects but at higher concentrations. The reciprocal nature of the nocturnal secretory patterns for LH and FSH and prolactin in this patient suggests an alteration in hypothalamic dopaminergic mechanisms which are thought to control the secretion of these hormones.

Two- to threefold variations in sleep length were observed in 12 subjects living on self-selected schedules in an environment free of time cues. The duration of polygraphically recorded sleep episodes was highly correlated with the circadian phase of the body temperature rhythm at bedtime and not with the length of prior wakefulness. Furthermore, the rate of REM (rapid eye movement) sleep accumulation , REM latency, bedtime selection, and self-rated alertness assessments were also correlated with the body temperature rhythm.

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.

Plasma luteinizing hormone, follicle-stimulating hormone, and estradiol were measured at 20-minute intervals for 24-hours in seven pubertal premenarchal girls whose sleep was monitored polygraphically. A circadian variation in plasma estradiol was demonstrated with the highest values occurring during the day (1400-1600 hours) and lowest values during sleep, a time when gonadotropin secretion was augmented.

Plasma luteinizing hormone (LH) and testosterone (T) were measured by radioimmunoassay in nine pubertal boys and three sexually mature young men at 20-min intervals for 24 h. Plasma LH and T were also measured in one boy during a delayed sleep onset study. Polygraphic monitoring was carried out to identify precisely sleep onset. Wakefulness, and specific sleep stages. In all nine pubertal boys the plasma T concentration fluctuated and was significantly higher during normal nocturnal sleep as compared to daytime waking. This increased T secretion during sleep was temporally linked to the characteristic pubertal sleep augmentation of LH secretion. To define further the relationship of this increased T secretion to sleep, plasma LH and T were also measured in three of the pubertal boys after acute (1-day) reversal of the sleep-wake cycle. One of these boys was also studied after 3 days of sleep-wake cycle reversal. The results of these studies showed that plasma T was now augmented during the reversed daytime sleep period; the mean T concentrations during this period were significantly higher (P < 0.001) than during nocturnal waking in all four studies. Measurement of plasma LH and T in the three sexually mature young men showed episodic secretion of LH and T during both waking and sleep periods; there was no consistent significant augmentation of LH or T secretion during sleep. This study demonstrates that (a) in normal pubertal boys and sexually mature young men plasma T fluctuates episodically; (b) there is marked augmentation of T secretion during sleep in pubertal boys, which is dependent on increased LH secretion; (c) this pubertal LH-T secretory “program” is dependent on sleep, since it shifts with delayed sleep onset and reversal of the sleep-wake cycle; and (d) this demonstrable tropic effect of LH on T is evident only during puberty, since sexually mature young men fail to show any consistent relationship between LH and T secretion either awake or asleep.

1. 1. Plasma cortisol concentration (PCC) was determined in euthermic woodchucks (M. monax) for 3 consecutive days at hourly intervals. Cortisol was secreted in a highly episodic manner throughout the 24-hr day. Within 2 hr of lights on PCC rose sharply, but transiently. PCC was significantly higher during the lights on portion of the experiments. At lights off, cortisol levels fell and remained low until a few hours before lights on. 2. 2. The major peak of cortisol release was in the early morning, usually between 0600 and 0900 hr. A second smaller peak was found just before lights off (2000 hr). The cortisol secretion pattern strongly suggests a circadian rhythm of cortisol is present in euthermic woodchucks. 3. 3. There was no significant difference in cortisol concentration between fall and spring animals, and there was no difference between ages. Thus, cortisol secretion continues during the fall when the adrenal cortex is presumed to be involuted in preparation for hibernation.

A 6-year-old girl had subacute onset of hypoventilation and apnea during sleep. Diffuse dysautonomic changes were identified, including dilated, nonreactive pupils, decreased tearing and sweating, and abnormal temperature and cardiovascular control. All-night polysomnographic studies revealed frequent obstructive and central sleep apnea episodes. Her serum contained cytotoxic antineuroblastoma immunoglobulins. She died two years later during sleep. The general pathological examination revealed a ganglioneuroma originating in the sympathetic ganglia. Abnormalities in the brain were confined to the brainstem and consisted of complete loss of neurons with severe fibrillary gliosis in the region of the Edinger-Westphal nuclei as well as loss of neurons with gliosis in the locus ceruleus and in the reticular formation bilaterally.

A sensitive and specific RIA for melatonin has been validated for human plasma. Five young adult men had plasma samples obtained every 20 min during two 24-h periods. One was a normal active period and the other a basal period with complete bed rest. Melatonin was found to be secreted episodically throughout the 24 h in each condition, with secretory episodes clearly present during the waking day in the presence of bright light.

On 4 separate occasions 17–20 mg of cortisol was given intravenously for 4.5 to 6.5 hr at different times of the day to an adult male. Endogenous cortisol secretion was suppressed for 4.5–5.5 hr following cessation of the infusion, and was reinitiated after this period of suppression of secretory activity in a pattern similar to that observed during the same portions of the control days. The study supports the concept that the episodic 24-hr ACTH-cortisol secretory pattern is not directly determined by a sequence of high or low plasma cortisol concentrations, but rather regulated or “programmed” for recurrent shorter time periods linked to the 24-hr sleep-wake cycle.

In order to test the hypothesis that cortisol secretion is inhibited during sleep, six healthy young men (ages 18-24) were studied in a 4-day protocol. A baseline nocturnal sleep period was followed by one night's total sleep deprivation, then sleep at 180 degrees phase shift, and then return to a normal nocturnal sleep episode (SP-3). Plasma cortisol concentrations were measured every 20 min (obtained by an indwelling venous catheter), rectal temperature was measured every minute, and sleep was polygraphically defined. During the first 4 h of sustained sleep, cortisol secretion was decreased even when sleep occurred during a time when the subject was usually awake; conversely, it was elevated if awake at the usual daily time of sleeping. This was not the case for the last 4 h of sleep. Body temperature was also decreased but during each entire 7- to 8-h sleep period. Meals produced only a small brief rise of cortisol and produced no change in body temperature. Stage 4 sleep was increased during the 180 degrees inverted sleep episode and decreased during SP-3, REM sleep however was increased during SP-3. A reciprocal relationship was found between REM and stages 3 and 4 for the second, third, and fourth, and sixth h of sleep for SP-3. These results demonstrate the inhibitory effect of the behavioral complex of sleeping on cortisol secretion superimposed on its endogenous circadian and ultradian rhythm. These neurophysiological events may be used to entrain and time the period and phase of biological rhythms in relation to shift work, sleep deprivation, and transmeridian jet travel.

Investigations in recent years have shown that secretion of pituitary hormones is episodic rather than continuous, manifesting endogenous rhythms that are largely governed by the 24-hour sleep-wake cycle. Variance from normal secretory patterns has been observed in several clinical syndromes (among them acromegaly, Cushing's, and affective depressive illness) and already serves as a valuable diagnostic tool.

(1978). Polysomnographic Recording Techniques Used for the Diagnosis of Sleep Disorders in a Sleep Disorders Center. American Journal of EEG Technology: Vol. 18, No. 3, pp. 107-132.

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.

The relationship between plasma levels of the tricyclic antidepressant desmethylimipramine (DMI) and plasma levels of melatonin-like immunoreactivity was studied in 32 endogenously depressed patients. An inverse correlation between plasma levels of DMI and plasma levels of melatonin-like immunoreactivity was found in the group of clinical responders to the chronic administration of the drug. The nonresponders had higher levels of melatonin-like immunoreactivity at comparable levels of DMI. This findings is consistent with the hypothesis that chronic high plasma levels of DMI may down-regulate the β-adrenergic receptors in man. However, some other homeostatic mechanisms may be involved in the clinical response.

All biological organisms demonstrate chronobiological rhythms which characterize their responses to both short-term and long-term environmental changes. All the hypothalamic and pituitary and many but not all of the peripheral endocrine hormones have been shown to have complex periodic patterns of secretion and circulation in the blood.

—Studies were carried out on a group of six young (ages 23–30) and six older (ages 53–70) normal men who lived under conditions of temporal, but not social isolation, from three to eight weeks. During entrained and non-entrained (free-running) conditions, comparative measurements were made of sleep-wake cycles, sleep stages and rectal temperature rhythms for these two age groups. Results demonstrated a reduction in the period and amplitude of the body temperature rhythms during free-running in the older group. Sleep efficiency, total sleep time, REM sleep latency, REM episode length, percent REM in the last 2 hours of sleep, the length and frequency of arousals during sleep, and the terminal wake latency were all age related and dependent on entrainment. The period of the sleep-wake cycle, terminal awakenings from REM and percent REM in the first 3 hours of sleep were not age related but were dependent on entrainment. Sleep stages as percents of total sleep time were found to be age related but independent of entrainment, while sleep latency, mid-REM to mid-REM cycle length and the ratio of sleep to total time were neither age related nor dependent on entrainment. In addition, individual chronobiological differences were prominent in the older group. Changes of period and of the phase relationship of sleep-wake and temperature rhythms occurred in several subjects during the non-entrained condition.

In a previous publication, prepubertal depressives were found not to exhibit a shortened REM period latency during active illness when compared with pathological and normal control groups. It was hypothesized that this might be due to a nonselective inhibition of REM sleep by slow-wave sleep (SWS), which is quite intense among prepubertal children, especially during the first 2 h of the sleep period. A number of polysomnographic signs normally associated with REM sleep were observed to occur periodically, prior to the beginning of the first REM period. It was thought that these signs might be indicative of "minor escapes" of REM sleep activity from the inhibitory influence of SWS. It was further hypothesized that differences among the experimental groups in the occurrence (timing and amount per minute) of these signs support the idea of an inhibitory effect of SWS on REM; and thus offer an explanation for the apparent dissociation between the depressive disorder among prepubertal children and a shortened REM period latency. The hypotheses were not supported by the results presented here indicating that the above dissociation is probably not due to inhibitory mechanisms of SWS on REM sleep.

Theoretical and technical problems in using Nocturnal Penile Tumescence (NPT) measurements for the differential diagnosis of impotence are discussed and possible solutions are offered: 1) The basic assumption that NPT measurements can distinguish psychogenic from organic impotence has never been demonstrated in patients shown to be psychogenically and organically impotent independent of the NPT measurements themselves. Studies attempting to do this are necessary to determine definitively the limits of the clinical applicability of this important diagnostic tool. 2) Evidence is presented showing that though a direct observation of one of the patient's fullest erections is required for an adequate NPT evaluation, this is not always done. The danger of misdiagnosis if this step is omitted is illustrated with a case report. 3) Disagreements in the literature about NPT criteria for diagnosing psychogenic impotence are discussed and criteria are suggested that are based on demonstrating the intactness of the physiological mechanisms required for erection rather than on values recorded in normal subjects.

— Man is the only eukaryotic organism in which it has been reported that the circadian system cannot be entrained to a 24-h period by a simple light-dark (LD) cycle. In this paper, we reexamine the evidence for that claim and demonstrate that there were some fundamental flaws in the experimental design of the previous studies on which this conclusion was based. We report new studies in which we tested the efficacy of LD cycles in entraining the circadian rhythms of human subjects living in isolation from environmental time cues. We found that the cyclic alternation of light and dark, when applied to human subjects in a comparable way to experiments in other species, was an effective entraining agent. Our results and a critical review of the literature indicate that a LD cycle alone can be an effective environmental synchronizer of the human circadian timing system. Other factors, such as the knowledge of time of day, social contacts, the feeding schedule, and the imposed rest-activity schedule may contribute to stable entrainment, although their relative strengths as synchronizers have yet to be determined.

Plasma growth hormone measured at 20-min intervals across the night via indwelling venous cannula revealed a significant reduction in 16 healthy aged men as compared with 14 healthy young men. The decrease in growth hormone was entirely confined to the first 3 hours of the night (M +/- SEM for the integrated level was 5.0 +/- 1.2 and 21 +/- 4.2 ng . hr/ml). Growth hormone across the latter part of the night did not differ. Day and evening growth hormone levels measured hourly in five of the aged and nine of the young men failed to reveal an age effect. Growth hormone release is known to be associated with sleep onset, and particularly with slow wave sleep, stage 3 and 4, which was reduced in amount in these aged men (9.9 +/- 1.9 and 22.8 +/- 2.3% of time in bed for aged and young groups, respectively). Sleep stage 3 and 4 correlated significantly with growth hormone level (R = .463, p less than .01) for young and aged men combined, but not for either age group alone, indicating that growth hormone does not have a direct, simple relationship with slow wave sleep.

1. 1.|Plasma catecholamines (dopamine, norepinephrine and epinephrine) were measured in non-hibernating (summer) and hibernating woodchunks (Marmota monax). Summer animals were warm (24°C) or cold (9°C) adapted for 3 weeks before blood samples were collected. 2. 2.|In summer, norephinephrine (NE) concentration after cold acclimation was double the level found at warm ambient temperature. Epinephrine (E) and dopamine (DA) concentrations were not significantly different between warm and cold acclimation. 3. 3.|During entrance into and in deep hibernation, all catecholamine values were significantly lower than cold-adapted levels. With arousal from hibernation, all catecholamines rose markedly above the summer values. The variation in plasma catecholamine levels reflect dramatic changes in the adrenosympathetic axis during all stages of hibernation.

Prolactin secretion in normal adults is characterized by periods of episodic secretion which increase in magnitude during sleep. In this study, we report the 24-h mean prolactin concentrations, prolactin secretory patterns, and associated pituitary hormone function in nine patients (seven women and two men) with hyperprolactinemia of diverse etiologies. Four of the women and one of the men had clinically demonstrable pituitary tumors, one boy had a hypothalamic tumor, and the three other women had “functional” hyperprolactinemia. The 24-h mean prolactin concentrations derived from averaging the 20-min interval samples for 24 h ranged from 28.6 to 1,220 ng/ml. The plasma prolactin patterns in these patients showed persistence of episodic secretion in all and loss of the normal sleep-wake difference in plasma prolactin in seven of nine. Three of the patients with galactorrhea and comparable 24-h mean prolactin concentrations (58.3, 59.7, and 64.3 ng/ml) showed similar prolactin secretory patterns despite different etiologic mechanisms. Evaluation of the secretory patterns of luteinizing hormone (LH) in these patients showed loss of normal pulsatile LH release and a low 24-h mean LH concentration in the patient with the pituitary tumor, while the two patients without clinically demonstrable pituitary tumors (“post-pill” galactorrhea and “idiopathic” galactorrhea) showed normal LH secretory patterns and 24-h mean LH concentrations. The 24-h mean cortisol concentrations and secretory patterns were normal in five of the seven patients who had these parameters measured. The patient with the hypothalamic tumor had a low 24-h mean cortisol concentration and production rate and absent response to metyrapone. The patient with “idiopathic” galactorrhea had an elevated 24-h mean cortisol concentration but normal cortisol production rate and urinary 17-hydroxycorticoid excretion. Growth hormone secretion was abnormal in four of the patients (one with the hypothalamic tumor and three with pituitary tumors). Thyrotropin-releasing hormone (TRH) administration in four patients resulted in normal TSH release in two patients (one of whom developed galactorrhea after the test), an absent response in the patient with the hypothalamic tumor, and a blunted response in one of the women with a pituitary tumor. The two men had low 24-h mean plasma testosterone concentrations (69 and 30 ng/100 ml) and symptoms of impotence and loss of libido. Five of the women (four with pituitary tumors and one with Chiari-Frommel syndrome) had either low 24-h mean LH concentrations, abnormal LH secretory patterns, or both. These data indicate that patients with hyperprolactinemia encompassing a varied etiological range frequently show loss of the normal sleep-associated increase in prolactin secretion as well as abnormalities in the regulation of the other hypothalamic pituitary-regulated hormones. The finding that the abnormalities in LH, growth hormone, thyrotropin, and cortisol (adrenocorticotrophic) secretion were almost uniformly confined to the patients with the clinically demonstrable hypothalamic or pituitary tumors suggests that the size of the lesion is the critical factor.

Equimolar doses ofD-amphetamine and L-amphetamine, and a water placebo were injected intravenously on different days into rhesus monkeys, and their plasma cortisol and GH responses were determined over a 3-hour period. D- and L-amphetaniine (but not the placebo) equally suppressedplasma cortisol concentration and equally increased plasma GH concentration. Pretreatment of the monkeys with large doses of pimozide, a specific dopa- mine receptor blocker, did not appear to block the hormonal responses to either isomer of amphetamine. The results suggest that the hormonal responses to both D- and L-amphetamine were mediated by noradrenergic neurones stimulatory to GH and inhibitory to ACTH, and that D- and L-amphetamine exert equipotent noradrenergic effects in the neuroendocrine system.(Endocrinology 99: 459,1976)

We have observed three children who developed obstructive sleep apnea immediately following construction of pharyngeal flaps designed to improve the speech of these patients with velopharyngeal incompetence. Postoperatively the patients were noted to have repeated episodes during sleep of strong respiratory efforts without airflow. Sleep apnea can be debilitating and lethal, and should be looked for following surgery of the upper airway. Respiratory depressants should be avoided. Airway intubation, revision of the surgery, or tracheostomy may be necessary.

Obstructive sleep apnea syndrome was studied in 32 children, aged 2 to 14 years, in the sleep-wake disorders center at Montefiore Hospital and Medical Center during the years 1977 to 1980. All children under-went all-night polysomnograms; 17 of these children had surgery to relieve airway obstruction and seven had a repeat polysomnographic study 4 to 6 weeks following the surgery. There was a significant improvement in the number of obstructive apneas and in other apnea indices following surgery. There was no significant effect on the durations and the proportions of the various sleep stages, on sleep efficiency, or on the number of awakenings.

The temporal pattern of growth hormone release at sleep onset was studied in six adult human subjects by frequent blood sampling combined with polygraphic sleep recording. HGH release was associated with sleep onset but not with the transition from waking to sleep. Delta activity consistently preceded the first elevation of plasma HGH.

Twelve normal women with regularly recurring menstrual periods had electrophysiological recording performed and indwelling venous catheters inserted during 1–4 consecutive nights of sleep at mid-menstrual cycle. Four of these subjects were also studied during daytime waking activity. Plasma samples were collected at frequent intervals in order to study the temporal aspects of LH secretion. LH was measured by double-antibody radioimmunoassay. All subjects demonstrated episodic secretion of LH at a frequency (for major episodes) which resembled that of the human REM-non-REM sleep cycle. However, there was no correlation of plasma LH values with the stages of sleep. In addition, no difference in LH concentration was found between sleep and waking. During the LH surge, episodic secretion of LH continued and was superimposed on a rising baseline. Two subjects, who were studied sequentially before and during the LH surge, demonstrated sudden elevations of plasma LH concentration in the latter part of the sleep ...

To evaluate the secretory patterns of luteinizing and follicle-stimulating hormones in various forms of sexual precocity, plasma levels of these hormones were measured every 20 minutes for 24 hours in six patients and nine normal pubertal children. Three patients with "idiopathic" precocious puberty and one boy with a hypothalamic tumo rand precocious puberty exhibited fluctuating plasma concentrations that resembled findings in normal pubertal children in that they had significantly increased luteinizing hormone concentrations during sleep. Two boys with congenital adrenal hyperplasia and advanced bone age also showed episodic fluctuation of both hormones and augmented luteinizing hormone concentrations during sleep. These findings show that patients with precocious puberty related either to Central-nervous-system stimulation or to a primary adrenal disorder can exhibit the normal pubertal luteinizing hormone pattern of augmented secretory activity synchronous with sleep. (N Engl J Med 289:282–2...

Plasma luteinizing hormone (LH) was measured by radioimmunoassay at 20-min intervals for 24-hr in 5 normal men before and after the daily administration of 100 mg clomiphene citrate for 7 days. The results showed that clomiphene caused a significant (P < 0.001) increase in the 24-hr mean LH concentration in all 5 subjects. The range of the percent increase was 135–245 with a mean of 180%. In spite of the highly significant increase in the 24-hr mean LH concentration there were instances of overlap of isolated LH values in the control and clomiphene studies. Analysis of the 24-hr plasma curves showed that the increased mean LH concentration was achieved by either increasing the amount of LH secreted per secretory episode or the number of major secretory episodes or both. Calculation of the LH production rate from the 24-hr LH secretory patterns showed a mean percent increase of 189% with a range of 149–259. Estimation of the LH “half-life” from the declining phase of the secretory episodes showed a cluster...

Polygraphic recording is presented of the sleep pattern in a young male who developed nystagmus and oscillopsia associated with a remittent CNS demyelinating disease. The vestibular nystagmus observed during wakefulness disappeared during all stages of sleep, including rapid eye movement sleep (REM). Since vestibular nystagmus experimentally induced in wakefulness is also absent during all phases of sleep, these findings suggest that during sleep similar suppressive mechanisms are operative.

Plasma samples were collected every twenty minutes from each of five normal women and luteinizing hormone was measured by radio-immunoassay. Plasma concentrations of luteinizing hormone were decreased in the first part of the sleep period with the maximum drop occuring during the third hour following stage II onset. Analysis of similar data from a group of five normal men revealed no significant differences in the LH secretory pattern between waking activity and sleep or between the two halves of the sleep period. Analogy was made with the differential capacity of the hypothalamus in males and females to release LH cyclically. Speculation was offered on the possible role of the pineal gland in the sleep-related changes of LH secretion in women.

The behavioral, EEG, and auditory responses have been studied during the maturation of prematurely born infants. It was found that: (1) The less mature the infant, the less time spent in a quiet sleep state. As the infants matured, periods of quiet sleep occurred for longer durations and interrupted the active sleep phase more frequently. (2) The EEG pattern of young infants (23–26 weeks estimated conceptional age [ECA]) consisted almost entirely of an “intermittent” pattern. As maturation progressed, this “intermittent” pattern became more closely associated with periods of quiet sleep. The continuous pattern appearing at approximately 29 to 31 weeks (ECA) was increasingly associated with an active sleep phase; by 34 to 35 weeks (ECA), the correspondence between EEG pattern and sleep state was more constant. (3) All infants regardless of conceptional age responded to the auditory stimulus from all recorded areas of the scalp. A sequence of wave patterns of the auditory evoked response was noted as a function of maturation. The young infants had a large, negative, long-latency (180–270 msec) wave diffusely over the scalp. As maturation progressed, a series of negative-positive-negative components was recognized. The evoked response patterns changed wave latency-amplitude relation as a function of both age and scalp topography. (4) The latency of the evoked response waves N1 and P2 were consistently greater during the intermittent, compared to the continuous EEG pattern in infants 34 to 40 weeks age post conception. (5) A small, (early ∼ 15 msec) auditory evoked response was recorded from the ear electrode and is probably of muscle origin. This early muscle response was augmented when the baby was awake and crying, intermediate in amplitude during an active sleep period, and barely detectable or absent during quiet sleep.

It has recently been demonstrated that the total daily production of cortisol by normal man is accomplished in a series of discontinuous secretory episodes (Fig 1) separated by periods of quiescence of the adrenal cortex (1). In the normal it was shown that the adrenals did not secrete cortisol for about 18 hours of each day. The proof was based upon measurement of the specific activity of plasma cortisol in association with rises and falls in the plasma cortisol concentration measured at brief intervals. Rises in plasma level were accompanied by drops in cortisol specific activities while falls were associated with unchanged specific activity. It was also demonstrated that this episodic secretory activity persisted throughout the 24 hour sleep-awake cycle. It was of considerable importance to establish whether a similar pattern of secretion existed in Cushing's syndrome due to bilateral adrenal hyperplasia. It has been possible to study a carefully selected patient and to resolve the problem with the fin...

Normal full-term newborn infants have been studied during a 3-hour period in which EEG, EMG, EKG and eye movements were recorded. Plasma HGH samples were obtained every 20 to 30 minutes in some infants by indwelling venous catheter, but in most by heel stick. Five infants of 2 days of age and eight infants between 4 and 8 days of age were studied. In the 2-day-old group studied findings for the average plasma HCH in mµg/ml (mean ± S.E.) following at least 5 minutes of sleep (active and quiet) were 33.4 ± 7, 52.8 ± 11, and 43.5 ± 36 following 5 minutes of waking. Comparable values for the 4-to 8-day-old group were 9.1 ± 1.1, 9.5 ± 1.3, and 8.3 ± 1.2. Wide variation in individual samples was found for the 2-day-old's (3 to 150 µg/ml) while this was less so for the older groups (0 to 20.2 mµg/ml). However, only three samples out of a total of 95 had values less than 1 mµg/ml. It thus appears that no clear correlation between plasma HGH levels and sleep-wake cycles was evident in these infants. It is likely that as with other biologic rhythms, HGH rhythmicity develops at a later stage of cerebral maturation.

Plasma LH and FSH concentrations were measured every 20 min for 24 hr in 3 patients with gonadal dysgenesis (12, 18, and 26 yr old). A 12-yr-old girl with Turner's syndrome showed augmented LH and FSH secretory activity synchronous with sleep similar to normal pubertal girls, but with gonadotropin levels in the castrate range. An 18-yr-old girl with pure gonadal dysgenesis had a statistically significant higher mean LH concentration during sleep compared with waking; however, the difference was less striking compared with the 12-yr-old. This diminution in the sleep-wake LH difference is also characteristic of normal late adolescents. A 26-yrold woman with Turner's syndrome did not show increased LH or FSH secretory activity during sleep which is similar to what has been reported in normal women. These findings suggest that patients with gonadal dysgenesis follow a qualitative pattern of gonadotropin secretion during sexual maturation which is similar to normal, but the concentrations of gonadotro...

The maturation of the nervous system of two groups of infants of low birth weight was estimated by the results of a standardized clinical neurologic examination and by evaluation of the electroencephalographic responses to auditory stimuli (clicks). Algebraically summed responses to clicks were recorded simultaneously from 10 scalp electrodes, using a standard electroencephalograph, tape recorder, and a computer of average transients. The results obtained by the two methods were compared with the age postconception, estimated from the maternal history. One group consisted of infants whose birth weights were below the 10th percentile for their gestational age (37.1 ± 2.0 weeks); the other group consisted of infants whose birth weights were similar to the first group but were between the 25th and 75th percentile for their gestational age (31.0 ± 2.3 weeks). In the small-for-age infants, the electroencephalographic responses and the neurologic reflexes were more mature than in the infants of similar birth weights who were not small for age. The results of both examination methods correlated well with the estimated postconception age but less well with birth weight, postnatal age, or somatic growth.

Fully developed nystagmus present in five Ss with congenital nystagmus while awake with eyes open or closed did not appear during the REM or non-REM sleep phases. However, rapid conjugate eye movements were present during REM sleep in all five Ss, and could not be distinguished from the patterns recognized in normal subjects.

The meal patterns of men who were initiating meals for extended periods in the absence of time cues were examined. A significant, positive correlation was found between the sizes (in kcals) of mixed and varied meals and the lengths of postprandial intervals. This quantitative relationship between meal size and meal timing is similar to patterns reported for freely feeding rats. If postprandial correlations reflect a short term mechanism for energy regulation then when humans schedule their meals due to social or time considerations they may negate this contribution to the regulation of their energy intake.

Une perfusion continue de melatonine diminue de facon significative les taux permatiques de LH chez des femmes menopausees. Cette experience plaide en faveur d'un effet antigonadotrope de la melatonine

The recent development of precise and sensitive radioimmunoassay methods for the measurement of human prolactin has resulted in a large body of data concerning the regulation of this hormone in phy...

There are circadian (approximately 24 h) rhythms for a wide range of human physiological and psychological functions including mood and performance efficiency. These rhythms are self-sustaining in conditions of temporal isolation, indicating that internal oscillators (or biological clocks) control them. Recent research has proposed an endogenous two-oscillator model of the human circadian system, with one oscillator indicated by the core body temperature rhythm and a second oscillator responsible for the daily cycle of sleep and wakefulness. The present study was designed to produce a desynchronization in period between the two oscillators, to assess directly the behaviour of the rhythms of different performance tasks. The results, reported here, indicate that a simple manual dexterity task is almost entirely under the control of the temperature rhythm oscillator, whereas a more complex cognitive task demonstrates a periodicity which appears to be influenced by those oscillators controlling temperature and the sleep/wake cycle.

The amount of time that monkeys (Macaca mulatta) slept was reduced after they were given p-chlorophenylalanine, a selective depletor of serotonin in animal tissues. The time spent in the rapid eye movement stage of sleep was unchanged, but the time in other sleep stages decreased. Seven regions of the brain had a 31 to 46 percent decrease in serotonin content; the concentration of cerebellar serotonin increased by 44 percent.

• We performed a three-night polysomnographic study of 54 rigorously assessed, drug free, prepubertal children who fit unmodified Research Diagnostic Criteria for major depressive disorder, and two groups of nondepressed controls (25 with emotional disorders and 11 who were normal). The groups did not differ polysomnographically, even though a high proportion of depressives and neurotics reported sleep disturbance in structured interviews. Sleep stage data do not appear to differentiate children with prepubertal major depressive disorders from nondepressed neurotic or normal children. Other psychobiologic findings in prepubertal depressives together with marked age effects on polysomnographic correlates of adult major depressive disorders suggest the hypothesis that polysomnographic abnormalities in adult major depressives are secondary to an interaction between depression and age.

Plasma growth hormone (GH) concentrations were determined every 20 minutes during sleep in 71 prepubertal children: 22 had endogenous major depressive disorder, 20 had nonendogenous major depressive disorder, 21 had nondepressed neurotic disorders, and eight were normal. Both depressive groups secreted significantly more GH during sleep than did controls. Measures included maximal GH plasma peak and area under the curve (AUC) during the total sleep period, during the first three hours after sleep onset, and during the first five hours after sleep onset. An AUC cutoff of 2,000 ngx min/mL Identified positively half the prepubertal children with major depression; with a specificity of 78% ( v neurotics) and 100% ( v normal children). Increased GH secretion during sleep may be a marker of illness, a past episode, or trait for prepubertal major depression regardless of endogenicity.

A case of impotence with significantly impaired nocturnal penile tumescence (NPT) following transurethral resection of the prostate (TURP) is described. The patient was studied with polysomnographic recording including measurements of NPT for three consecutive nights at nine months after surgery and showed a total absence of full erections. Possible causes of his impotence are discussed. It is concluded that the total clinical picture strongly suggests that the erectile dysfunction was a result of physiologic complications of the surgery. Methodologic problems in past work are discussed, and the need for detailed diagnostic studies is stressed. The sleep studies that should be a part of this comprehensive evaluation are described.