Biomedical subjects

H L Fehm

Publications and source records attributed to H L Fehm.

At least 127 records · Page 7Linked to original sources

PubMed1994

Scalp recorded direct current potential shifts associated with the transition to sleep in man.

Cortical direct current (DC) potentials are considered to reflect the state of cortical excitability which may change characteristically from wakefulness to sleep. The present experiments examined changes in the scalp recorded DC potential in 10 healthy humans at the transition from wakefulness to nocturnal sleep. For each subject, DC recordings obtained from Cz were evaluated for a 15 min pre-sleep onset interval and for a 20 min post-sleep onset interval, on 2 separate nights. Sleep stages were determined from standard sleep recordings. The transition from wakefulness to sleep coincided with a significant (P < 0.05) shift in the DC potential of negative polarity. Maximum negative potentials of (mean +/- S.E.M.) 500 +/- 130 microV (first night) and of 760 +/- 200 microV (second night) were reached at the end of the 20 min post-sleep onset interval. A number of possible technical and biological artifacts were controlled. It is reasonable to assume that the slow negative shift of the DC potential at the transition from wakefulness to sleep reflects increased cortical excitability. Whether the negative potential shift pertains during sleep, or is of transient nature and closely linked to the process of falling asleep, remains to be clarified.

Adolescent↗

PubMed1994

Comparison of satiating effects of ceruletide and food intake using behavioral and electrophysiological indicators of memory.

Animal and human studies have suggested a satieting effect of ceruletide, an analog of cholecystokinin. In humans, signs of a selectively diminished central nervous processing of food stimuli may provide a more valid measure of satiety than overt eating behavior. To assess the satieting effects of ceruletide in humans, effects of ceruletide and food intake on memory of food stimuli and stimuli not related to food (neutral and sex) were compared with memory performance in fasted subjects. In experiment I, recall of slide-projected words was tested in 12 fasting men in a within-subject comparison (i) following intravenous administration of saline solution, (ii) of ceruletide (6.75 micrograms), and (iii) after having eaten a regular breakfast. The P3 component of the event-related potential to the stimuli was assessed as a physiological sign of memory processing. In experiment II, recognition of pictures was tested in a between-subject design in 36 fasting men following (i) administration of saline solution, (ii) of ceruletide (6 micrograms), and (iii) intake of an opulent meal. After food intake, recall and recognition of food and also of sex stimuli were diminished, but were increased for neutral stimuli. Ceruletide diminished recognition of food stimuli and increased that of neutral stimuli; similar effects on recall of food and neutral stimuli failed to reach significance. P3 amplitude did not reflect changes in memory performance. Memory of food stimuli declined after ceruletide as well as after food intake, suggesting ceruletide mediates satieting effects on memory processing.

Adult↗

PubMed1994

Effects of menstrual cycle on creativity.

Seventeen healthy women (21-31 years) not taking oral contraceptives were tested at three phases of the menstrual cycle distinctly differing in hormonal patterns (menses, preovulatory phase, and midluteal phase). Phase detection was assured by determination of blood hormone concentrations. Another 17 women taking oral contraceptives (combined preparation of estrogen and progestin) served as age-matched controls, and were tested during menses and during phases corresponding to preovulatory and midluteal phase. On each test occasion, aspects of creativity were assessed by a battery of six tests measuring "semantic" and "figural" abilities of divergent thinking. Additionally, a test of motor perseveration (Mittenecker-Zeigeversuch) was presented. During the preovulatory phase, creativity was in general improved when serum concentrations of estrogen (E2) and luteinizing hormone (LH) were highest whereas motor perseveration decreased. In control women, there was no preovulatory improvement of divergent thinking and no preovulatory decrease in motor perseveration.

Adult↗

PubMed1994

Cholinergic potentiation of the meal-related rise in ACTH and cortisol concentrations in men.

The present study examined the influence of physostigmine, an acetylcholine esterase inhibitor, on the secretory activity of the hypothalamo-pituitary-adrenocortical (HPA)--axis under basal (experiment I) and stimulated (experiment II) conditions in young healthy men. In a third experiment, the effect of scopolamine, a muscarinic acetylcholine receptor antagonist, on HPA secretory activity after physiological stimulation was tested. The experiments started between 09.00 and 10.00 a.m.. After a resting period of 1.5 h, either physostigmine (0.0125 mg per kg body weight soluted in isotonic saline) or placebo (saline) was infused within 15 min. In experiment I subjects (n = 7) remained fasting while in experiment II (n = 18) a standardized lunch was offered after the infusion. Experiment III (n = 7) was designed as experiment II but instead of physostigmine, scopolamine or placebo (0.5 mg) was subcutaneously injected 105 min before the meal. Blood for the determination of ACTH and cortisol was drawn in regular intervals during the experiments. Physostigmine did not change basal ACTH and cortisol secretion per se, excluding activation of basal HPA secretion due to acetylcholineesterase inhibition and its non specific side effects. Meal intake stimulated ACTH and cortisol secretion which was significantly enhanced when physostigmine was administered (p < 0.05). Scopolamine did not influence the meal related ACTH and cortisol secretion. These findings demonstrate that cholinergic neurotransmission is able to increase ACTH and cortisol concentrations in humans. This effect seems to be complementary to other stimulatory neurotransmitter systems, and is functional during stimulated HPA secretory activity and not under basal conditions.

Adrenocorticotropic Hormone↗

PubMed1994

Effects of vasopressin on event-related potential indicators of cognitive stimulus processing in young and old humans.

BACKGROUND: Vasopressin has been shown to improve electrophysiological signs of cognitive stimulus processing in young human subjects. This study compared the effects of arginine vasopressin (AVP) on central nervous stimulus processing in old and young mentally healthy subjects. To assess aspects of cognitive stimulus processing, event-related potentials (ERPs) were recorded. METHOD: A total of 22 old and 28 young subjects were tested on two subsequent days. Substances were administered intranasally 22, 12, and 1 hour(s) prior to experimental sessions. Prior to the first session, all subjects received placebo. Prior to the second session, 11 of the elderly and 15 of the young subjects received AVP (3 x 10 IU in each nostril) while the remaining subjects again received placebo. The study was held double blind. The subjects performed an auditory "oddball" task consisting of rare target tones (requiring a button press response) interspersed throughout a sequence of frequent standard tones while an electroencephalogram was recorded. RESULTS: Differences between young and aged subjects were more pronounced for ERPs to targets than standard pips. Latencies of the N2 and P3 waves of the ERP to targets were significantly prolonged, and the P3 amplitude was diminished in the elderly subjects (p < .01). N2 amplitude was enhanced in both age groups by vasopressin (p < .05). However, AVP treatment significantly enlarged the N2-P3 difference amplitude only in young subjects. CONCLUSIONS: The results indicate that AVP improves ERP signs of stimulus processing associated with attentional mechanisms. However, the ERP signs of age-related cognitive impairment remained unimproved after AVP.

Administration, Intranasal↗

PubMed1994

Effects of insulin and hypoglycemia on the auditory brain stem response in humans.

1. This study aimed to differentiate effects of insulin and hypoglycemia on sensory brain stem functions in humans. Auditory brain stem responses (ABR) were examined in 30 healthy men during euglycemia and after 20 and 50 min of steady-state hypoglycemia of 2.6 mM induced with human insulin (HI) in one session and porcine insulin (PI) in another session. 2. Levels of blood glucose and serum insulin were identical in both sessions during HI and PI infusion. 3. Hypoglycemia increased interpeak latencies III-V (+71 microseconds; P < 0.001) and I-V (+123 microseconds; P < 0.001), whereas changes in the latency of wave I were not significant. 4. After 20 min of constant hypoglycemia, increases in the interpeak latencies I-V and III-V were significantly more pronounced during infusion of PI than HI. These differences disappeared with time spent in hypoglycemia, i.e., after 50 min of hypoglycemia. 5. Apart from the delaying effect of hypoglycemia on neuronal transmission within the sensory brain stem, the results provide evidence for a separate influence of insulin on these functions.

Adolescent↗

PubMed1994

Sleep and wakefulness affect the responsiveness of the pituitary-adrenocortical axis to arginine vasopressin in humans.

The secretory activity of the pituitary-adrenocortical axis at night is characterized by a quiescent period during the first hours of sleep, preceding a period of enhanced activity in the early morning hours. It is still controversial whether the typical nocturnal secretory pattern of adrenocorticotropic hormone (ACTH) and cortisol is a mere reflection of a circadian rhythm or whether mechanisms associated with the state of sleep influence the nocturnal secretion of these hormones. Here, we administered arginine vasopressin (AVP) to normal men during the first part of nocturnal sleep and compared the release of ACTH and cortisol with the release after a second administration during the second part of the same night and also with the release after administration of AVP at identical points of nighttime while subjects were kept awake in another night. Compared with wakefulness, the cortisol release in response to AVP was significantly lower during sleep, with this effect restricted to the early part of sleep. The ACTH release was lower after the first AVP administration during the early part of sleep as compared with the AVP injection during the second part of the same night. Our data demonstrate a sleep-associated inhibition of stimulated ACTH and cortisol release, suggesting a period of decreased responsiveness of the pituitary-adrenocortical axis during early sleep.

Adrenal Cortex↗

PubMed1994

Effects of diurnal sleep on secretion of cortisol, luteinizing hormone, and growth hormone in man.

Evidence has been provided for an influence of nocturnal sleep on the secretion of cortisol, LH, and GH in man. Although nocturnal sleep inhibits cortisol secretion during the first hours, it augments the secretion of LH and GH. To separate the effects of circadian rhythm from those of sleep, the present experiments examined the influence of diurnal sleep on the release of cortisol, LH, and GH in 12 young men. Subjects slept on 2 different occasions. After a night of wakefulness, subjects were assigned to bed at 0800 h the following morning. Lights were turned off either at 1100 or 1500 h to enable sleep. Effects of diurnal sleep were evaluated by comparing blood hormone concentrations during the interval from 1100-1500 h between subjects when sleeping and awake. Comparing hormonal concentrations during the 4 h of sleep after 1100 h with those during the 4-h sleep interval after 1500 h provided evidence for an influence of circadian rhythm on cortisol and LH release. Diurnal sleep, as has been shown for nocturnal sleep, augmented the secretion of LH and GH. However, in contrast to nocturnal sleep, diurnal sleep failed to suppress cortisol release, suggesting that sleep does not inhibit cortisol release at any point of its circadian rhythm, but only within a limited range of entrainment.

Adult↗

PubMed1994

Interleukin-6 stimulates the hypothalamus-pituitary-adrenocortical axis in man.

A recent study in humans, animal studies, and in vitro data have suggested that interleukin-6 (IL-6) stimulates the secretory activity of the hypothalamus-pituitary-adrenocortical (HPA) axis. In a phase II study, one female and six male patients with metastatic renal cell carcinoma received IL-6 to evaluate a possible antitumor effect of IL-6. This offered the possibility of investigating the influence of IL-6 on the HPA axis in man. The subjects were studied 1 day before, on day 1, and on day 21 of IL-6 therapy (150 micrograms administered sc every day at 0900 h). Blood samples were taken at 0900, 1100, 1300, 1600, and 2000 h the day before, on day 1 of IL-6 therapy, 24 h after the first IL-6 injection, and on day 21 of IL-6 treatment. Plasma ACTH and cortisol levels promptly followed the rise of IL-6, which peaked 4 h after administration. They were significantly (P < 0.05) higher at 1100 and 1300 h on day 1 of IL-6 therapy compared with the corresponding plasma levels the day before IL-6 treatment. Cortisol concentrations remained significantly increased at 1600 and 2000 h after IL-6 administration. Twenty-four hours after the first IL-6 administration, IL-6, ACTH, and cortisol levels had reached preinjection values. Although plasma cortisol levels were similar on days 1 and 21, ACTH levels were lower on day 21 (than on day 1), but significantly elevated at 1100 h compared with levels on the day before the first IL-6 injection. Results confirming the very recent data of another study demonstrate a stimulating effect of IL-6 on the HPA axis in man. They support the notion that IL-6 is one of the cytokines involved in the interaction between the immune system and the HPA axis.

Adrenal Cortex↗

PubMed1994

Basal secretory activity of the hypothalamo-pituitary-adrenocortical axis is enhanced in healthy elderly. An assessment during undisturbed night-time sleep.

The process of aging is characterized by a disturbed neuroendocrine regulation, including a changed secretory activity of the hypothalamo-pituitary-adrenocortical (HPA) axis. In the present study adrenocorticotropin (ACTH) and cortisol secretion was monitored during nocturnal sleep (controlled by somnopolygraphy) in healthy aged men (N = 10, aged range 70-92 years, mean 78.2 years) and women (N = 10, age range 70-88 years, mean 78.6 years), and in young male controls (N = 16, age range 20-34 years, mean 24.9 years). Blood was drawn every 15 min. Most important, basal HPA secretory activity was enhanced distinctly in the elderly, as indicated by significantly elevated nadirs of plasma cortisol and ACTH concentrations occurring during early nocturnal sleep (p < 0.001, compared to young controls) and by elevated average levels of cortisol and ACTH between 23.00 and 03.00 h (p < 0.001). The first rise in nocturnal plasma cortisol began, on average, 67 min earlier than in young controls (p < 0.005). Changes of endocrine activity were associated with marked reductions of slow-wave sleep (SWS, p < 0.05) and rapid eye movement (REM) sleep in the elderly (p < 0.01), while time awake and in stage 1 sleep was increased. The REM sleep coincided with decreased HPA secretory activity, irrespective of age, indicating that the link between the ultradian sleep structure and the secretory HPA activity is maintained in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1994

Evidence for effects of insulin on sensory processing in humans.

Systemic insulin passes the blood-brain barrier and insulin receptors have been detected in various brain regions. Yet, the biological significance of insulin acting on the brain remains rather unclear. Reports of different awareness of hypoglycemic symptoms during hypoglycemia induced by human insulin (HI) and porcine insulin (PI) suggest a modulatory influence of insulin on sensory processing. In a double-blind, within-subject, crossover comparison, we recorded visual-evoked potentials (VEP) in 30 healthy men during euglycemia and after 20 or 50 min of constant hypoglycemia of 2.66 mM (47.9 mg/dl) induced by HI and PI. Blood glucose and serum insulin levels were identical in both sessions. Hypoglycemia reduced amplitudes of the VEP components P1 and N2 and increased latencies of N1, P1, and N2. However, hypoglycemia-induced changes in VEP amplitudes and latencies were significantly stronger during PI and HI infusion: P1-N2 difference amplitude decreased from (mean +/- SE) 11.9 +/- 0.9 to 10.7 +/- 0.8 muV during HI and from 12.4 +/- 0.9 to 8.7 +/- 0.7 muV during PI infusion (P < 0.002). P1 latency increased from 112.0 +/- 3.2 to 118.8 +/- 3.2 ms during HI and from 114.0 +/- 3.3 to 126.3 +/- 4.6 ms during PI infusion (P < 0.05). Differences between the effects of the insulins were consistently apparent after 20 min of hypoglycemia, which indicates a short-term action of the hormone. The results add to those of a foregoing study demonstrating differential effects of HI- and PI-induced hypoglycemia on auditory evoked potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Auditory reflex thresholds elevated by stress-induced cortisol secretion.

To study steroid effects on auditory perception, 24 volunteers were unexpectedly confronted with a psychological stressor. Auditory reflexes to pure tones and noise were recorded before stress exposure, up to 100 min afterwards and in a second control session. Repeated measurements of cortisol and testosterone in saliva, as well as blood pressure, heart rate, and subjective feelings confirmed the stressful nature of the test. Following stress induction the auditory reflex of the contralateral ear needed significantly higher loudness (i.e. more decibels) to be elicited than at baseline or control measures. Two lines of evidence suggest that this stress-induced change may be specifically related to glucocorticoid actions: (1) In a previous study similar elevations in auditory reflex threshold had been obtained by the administration of exogenous glucocorticoids (hydrocortisone), and (2) in the present study the overall effect of stress induction on acoustic reflex described above was mainly observed in a subgroup of subjects, who responded to the stressor with a marked rise in free cortisol.

Acoustic Stimulation↗

PubMed1993

Entrainment of nocturnal pituitary-adrenocortical activity to sleep processes in man--a hypothesis.

The 24 hr patterns of plasma ACTH and cortisol concentrations are characterized by prominent circadian and ultradian oscillations. Usually both, nadir and acrophase of the circadian rhythm occur during sleep. This led us to re-evaluated the temporal relationship between sleep processes and nocturnal plasma ACTH and cortisol levels and the impact of several types of sleep manipulation (sleep delay, sleep disruption, sleep prolongation, sleep deprivation, and reversal of the sleep-wake cycle). Pituitary-adrenocortical activity appeared to be linked to the cyclic process of nocturnal sleep with inhibitory influences present during the first two sleep cycles. After initiation of the third sleep cycle stimulatory effects of sleep prevailed, lasting until awakening. The sleep associated influences appeared to act in concert with influences of circadian oscillators and resulted in an amplification of the circadian rhythm of pituitary-adrenal activity; they were strong enough to entrain the circadian rhythm of the pituitary-adrenal system to the sleep-wake cycle, as long as phase delays were moderate. However, with acute sleep-wake reversals the sleep associated influences were masked by the dominant effects of the circadian clock. In contrast, GH secretion appeared to be controlled primarily be sleep-associated mechanism with only minor circadian influences.

Adrenal Cortex↗

PubMed1993

Event-related brain potential correlates of self-reported hunger and satiety.

Perception of hunger and satiety was examined by means of event-related potential (ERP) recordings. On the basis of Helson's frame-of-reference theory, it was hypothesized that hunger is perceived with reference to an actual adaptation level. ERPs were recorded to adjectives (hungry, thirsty, tired) combined with one of five adverbs (very, almost, somewhat, hardly, not). Subjects indicated whether a particular adverb-adjective combination accurately described their actual feeling of hunger, thirst, or fatigue. They were tested after they had fasted for 16 hr and another time when they were satiated. Area of P300 of the ERP was smallest for adverb-adjective combinations agreeing with the subject's actual state of hunger (i.e., adaptation level), which was almost hungry in fasting subjects and hardly hungry in satiated subjects. These P300 minima were flanked by significantly enhanced (p < 0.001) P300 areas for the immediately adjacent adverbs combined with hungry. P300 areas for adverbs combined with thirsty and tired did not depend on the subject's state of hunger. The data suggest that perception of internal states, such as hunger, refers to an adaptation level that is sensitively indicated by P300 area.

Adult↗

PubMed1993

Antimineralocorticoid canrenoate enhances secretory activity of the hypothalamus-pituitary-adrenocortical (HPA) axis in humans.

In rats, both hippocampal glucocorticoid and mineralocorticoid receptors (MR) have been shown to participate in the regulation of basal hypothalamus-pituitary-adrenocortical (HPA) secretory activity. Inhibition of hippocampal MRs enhanced the activity of the HPA axis in these animals. We tested the influence of potassium cancrenoate, a selective MR antagonist, on basal cortisol secretion in 10 healthy young men during sleep. Cortisol, ACTH, vasopressin and growth hormone (GH) were determined at 22.00, 23.00, 01.00, 04.00 and 07.00 h. Sleep was monitored by somnopolygraphy. Potassium canrenoate (200 mg) was administered intravenously at 08.00 and 17.00 h the preceding day. Compared with a placebo condition, potassium canrenoate elevated cortisol levels throughout the night, with significant (p < 0.05) increases at 22.00, 23.00, 01.00 and 07.00 h. Effects of canrenoate on ACTH levels were not significant, and there was also no effect on plasma vasopressin levels. GH concentrations at 04.00 and 07.00 h were higher after canrenoate than placebo (p < 0.05). Changes induced by canrenoate paralleling those in animals after intracerebroventricular administration of MR antagonists suggest that central nervous MRs are involved in the regulation of HPA secretory activity also in humans.

Adult↗

PubMed1993

Impact of sleep on the circadian excursions in the pituitary gonadotropin responsiveness of early follicular phase women.

Whereas the nocturnal slowing of the LH pulse frequencies in the early follicular phase (EFP) of the menstrual cycle may be attributed to a sleep-associated increase in opioidergic activity, the concomitant augmentation of LH pulse amplitudes remains unexplained. We reasoned whether alterations in the pituitary gonadotropin responsiveness during the 24-hour rest-activity cycle may account for these enhanced LH pulse amplitudes during sleep. Accordingly, 12 EFP women (cycle days 3-5) were studied on 2 consecutive days during three occasions: a day time between 1000 and 1400 h (day studies), at night between 2200 and 0200 h, while the women were awake (night studies), and finally, during identical night hours, while the women were asleep (sleep studies). At all occasions, blood was collected at 10-min intervals for 4 h, while GnRH (25 micrograms) was administered twice within 2 h. During the day studies, prompt and sustained LH and FSH releases were noted in response to the first and second GnRH stimulations. However, the LH and FSH release after both the first and second GnRH challenges was markedly (P < 0.01) blunted during the night studies. By contrast, this decrease in LH, but not FSH response during the night was completely prevented, when GnRH was administered during sleep. Independent of the time at which GnRH had been administered, the second GnRH stimulations provoked much greater (P < 0.05 or less) LH and FSH releases than the first. Thus, a marked attenuation of the gonadotroph responsiveness is observed in EFP women during the night, and nocturnal sleep may eliminate this decline. Further, the priming actions on the gonadotrophs by repetitive GnRH stimulations are unaffected by the time of GnRH administrations. Collectively, these observations permit us to infer that the increased LH pulse amplitudes observed during sleep in EFP women may not be attributed to increased pituitary responsiveness.

Adult↗

PubMed1993

Systemic growth hormone does not affect human sleep.

Subsequent to sleep onset, GH concentrations increase markedly, suggesting a stimulatory influence of sleep on GH secretion. However, results have been inconsistent as to whether GH conversely exerts a significant influence on sleep. Hence, the effects of exogenous administration of GH and of GH secretion stimulated by GH-releasing hormone (GHRH) on sleep were reexamined in 3 experiments in healthy male volunteers. In Exp I, 12 men participated on 3 experimental nights, receiving a constant iv infusion of 5 IU GH (between 2100-0700 h), an im bolus injection of 5 IU GH at 2100 h, and placebo. In Exp II, the effects of a short iv infusion of a high dose of 48 IU GH (between 2345-2315 h) on sleep were evaluated in 3 men. In Exp III, the effects of continuous infusion of 30 micrograms/h GHRH (between 2200-0700 h) on sleep were compared to the placebo condition in 10 men. Experiments were double blind, within-subject, cross-over comparisons and included an adaptation night before experimental nights. On all nights, the subjects went to bed at 2300 h and were awakened at 0700 h. Administration of GH elevated plasma GH and somatomedin-C levels throughout the night (P < 0.005). Neither im administration of 5 IU GH nor iv administration of 5 and 48 IU GH had any effect on the total sleep time or the time spent in different sleep stages during the whole night or in the first and second halves of sleep time. Infusion of GHRH increased nocturnal GH secretion (P < 0.005), but the episodic pattern of GH secretion was maintained. However, sleep remained unchanged during GHRH infusion. From these results we conclude that in healthy man, systemic GH has no physiological role for sleep regulation.

Adult↗

PubMed1993

Corticotropin-releasing hormone-induced adrenocorticotropin and cortisol secretion depends on sleep and wakefulness.

Twenty-four-hour profiles of pituitary-adrenocortical secretory activity in humans are characterized by a distinct decrease in hormone secretion after sleep onset and a strong increase during the early morning hours. It is a widely accepted notion that this pattern of hormone secretion is driven by intrinsic circadian oscillators, and the contributions of sleep and wakefulness have been greatly neglected. Here, we examined whether there is a sleep-dependent inhibition of stimulated ACTH and cortisol release during early nocturnal sleep, which is dominated by slow wave sleep (SWS). We administered human CRH (hCRH; 50 micrograms), the main corticotropin secretagogue, to 14 healthy men during the first SWS period after sleep onset and another time in the same night during a period of stage 2 sleep in the second half of sleeping time. To discriminate possible circadian influences from influences of sleep, on a second night another two injections of hCRH were administered at identical points during the night to the same subject, who was kept awake. Exclusively during sleep, but only during SWS in the beginning of sleep time, ACTH and cortisol responses to hCRH were blunted. The results demonstrate an inhibiting influence of sleep on stimulated ACTH and cortisol secretion, with this effect restricted to the early part of sleep.

Adrenocorticotropic Hormone↗