Search PubMed⌕ Search

Biomedical subjects

H L Fehm

Publications and source records attributed to H L Fehm.

At least 55 records · Page 3Linked to original sources
PubMed2000

Interferon-alpha acutely impairs sleep in healthy humans.

We investigated the effects of two low doses of interferon-alpha (IFN-alpha) on nocturnal sleep in 18 healthy men by means of polysomnographic sleep recordings. At 1900h, human recombinant IFN-alpha (1000 or 10000 U/kg body weight) or placebo was administered subcutaneously. Between 2300h and 0700h subjects were allowed to sleep. In general effects were stronger at the dose of 10000 than 1000 U/kg body weight of IFN-alpha. Although, after IFN-alpha subjects experienced increased fatigue, the cytokine impaired the quality of nocturnal sleep. The higher dose of IFN-alpha suppressed slow wave sleep (17.8 +/- 2.0% vs 25.2 +/- 2.6% following placebo, P<0.003) but increased time spent in shallow sleep (P<0.05) during the first half of sleep time. Rapid eye movement (REM) sleep latency was postponed (P<0.02) and time spent in REM sleep was significantly decreased after IFN-alpha (P<0.04). The impairing influence of IFN-alpha on sleep in humans is in contrast with findings of sleep promoting effects of this cytokine in animals. Our data suggest that endogenous IFN-alpha may be a factor responsible for alterations of sleep, e.g. in the course of viral infections.

Adrenocorticotropic Hormone↗
PubMed2000

Changes in direct current (DC) potentials and infra-slow EEG oscillations at the onset of the luteinizing hormone (LH) pulse.

An essential function of the neuroendocrine system lies in the coordination of hypothalamo-pituitary secretory activity with neocortical neuronal activity. Cortical direct current (DC) potential shifts and EEG were monitored in conjunction with the circulating concentration of luteinizing hormone (LH) in humans while asleep to assess a hypothalamic-neocortical interaction. The onset of an LH pulse was accompanied (i) at frontocortical locations by a transient positive DC potential shift of approximately 3 min duration and peak amplitude 50 microV; (ii) at frontal and central locations by an increase in power of infra-slow EEG oscillations for periodicities between 64 and 320 s. Results uniquely demonstrate a coupling of hypothalamo-pituitary activity with regulation of neocortical excitability.

Activity Cycles↗
PubMed2000

Preserved hypothermic response to hypoglycemia after antecedent hypoglycemia.

Hypoglycemia is known to decrease the body temperature and to stimulate counterregulatory hormone secretion. Although it is well established that antecedent hypoglycemia reduces the hormonal response to subsequent hypoglycemia, the effects of antecedent hypoglycemia on the subsequent hypothermic response are obscure. In the present study, body temperature was measured orally during a total of 90 glucose clamp experiments in 45 healthy men. The clamps lasted 6 hours and were performed under 6 different experimental conditions: a euglycemic clamp with a low rate of insulin infusion, 1.5 mU/kg x min (low insulin-eu), a euglycemic clamp with a high rate of insulin infusion, 15.0 mU/kg x min (high insulin-eu), a hypoglycemic clamp with a low rate of insulin infusion, 1.5 mU/kg x min (low insulin-hypo), a hypoglycemic clamp with a high rate of insulin infusion, 15.0 mU/kg x min (high insulin-hypo), and 2 hypoglycemic clamps following an antecedent 2.5-hour hypoglycemia (56 mg/dL) induced by either a low (1.5 mU/kg x min, low insulin-ante-hypo) or a high (15.0 mU/kg x min, high insulin-ante-hypo) rate of insulin infusion. Plasma glucose was maintained normal during the euglycemic clamps and was decreased stepwise during the hypoglycemic clamps (76 --> 66 --> 56 --> 46 mg/dL). During the hypoglycemic clamps, body temperature decreased by 0.26 degrees +/- 0.09 degrees C in low insulin-hypo, 0.28 degrees +/- 0.09 degrees C in high insulin-hypo, 0.29 degrees +/- 0.09 degrees C in low insulin-ante-hypo, and 0.41 + 0.11 degrees C in high insulin-ante-hypo (all P < .01). There were no differences in the hypothermic response to hypoglycemia among the different hypoglycemic conditions (P > .1 for all comparisons). In contrast, body temperature remained unchanged during the euglycemic clamps, so the changes in body temperature differed significantly during the euglycemic clamps versus the hypoglycemic clamps (P < .05 for all comparisons). The data show that the body temperature decreases during hypoglycemia and this decrease is influenced neither by antecedent hypoglycemia nor by circulating insulin levels.

Adult↗
PubMed2000

Comparison of the inhibitory effect of insulin and hypoglycemia on insulin secretion in humans.

Although both insulin and hypoglycemia are known to inhibit endogenous insulin secretion, their potency to suppress insulin secretion has not been directly compared thus far. The serum C-peptide concentration was measured during 28 euglycemic and 28 stepwise hypoglycemic (4.1,3.6, 3.1, and 2.6 mmol/L) clamp experiments using either a low-rate (1.5 mU x min(-1) x kg(-1)) or high-rate (15.0 mU x mU(-1) x kg(-1)) insulin infusion. The experiments lasted 6 hours and were performed in 28 lean healthy men. During both the euglycemic and hypoglycemic clamps, serum insulin was approximately 40-fold higher during the high-rates versus low-rate insulin infusion (euglycemia, 24,029 +/- 1,595 v 543 +/- 34 pmol/L; hypoglycemia, 23,624 +/- 1,587 v 622 +/- 32 pmol/L). Under euglycemic conditions, serum C-peptide decreased from 0.54 +/- 0.04 to 0.41 +/- 0.05 nmol/L during the low-rate insulin infusion (P < .05) and from 0.55 +/- 0.07 to 0.27 +/- 0.09 nmol/L during the high-rate insulin infusion (P < .001). Under hypoglycemic conditions, serum C-peptide decreased from 0.50 +/- 0.03 to 0.02 +/- 0.01 nmol/L during the low-rate insulin infusion (P< .001) and from 0.46 +/- 0.07 to 0.02 +/- 0.01 nmol/L during the high-rate insulin infusion (P< .001). In the euglycemic clamp condition, the high-rate insulin infusion reduced the C-peptide concentration more than the low-rate insulin infusion (P < .05). Independent of the rate of insulin infusion, the decrease in C-peptide was distinctly more pronounced during hypoglycemia versus euglycemia (P < .001). These data indicate that insulin inhibits insulin/C-peptide secretion in a dose-dependent manner. Hypoglycemia is a much stronger inhibitor of insulin secretion than insulin itself.

Adult↗
PubMed2000

Increase in systolic blood pressure and catecholamine level during hyperinsulinemia in a placebo-controlled euglycemic clamp in healthy subjects.

Hyperinsulinemia has been shown to induce vasodilation and activation of the sympathetic nervous system. Whether these effects result in changes in blood pressure (BP) is discussed controversially. We measured BP and catecholamine levels in 50 healthy subjects during a 40-min baseline phase and during a 100-min euglycemic clamp phase. In a double-blind, between-subject comparison, 30 subjects were infused with 1.5mU insulin/kg x min, 20subjects were infused with saline solution. Insulin levels increased during insulin infusion from (mean+/-SE) 23.7 0.6 pmol/l to 406.2+/-3.0 pmol/l, but remained unchanged during placebo infusion. Blood glucose levels were identical during both conditions. Systolic BP increased from 116.6+/-1.5 mmHg to 119.8+/-1.8 mmHg during insulin infusion and decreased from 116.6+/-2.3 mmHg to 114.0+/-2.4 mmHg during placebo infusion (p<0.001, for the difference between the effects of insulin vs. placebo). Heart rate was higher during insulin infusion as compared to placebo infusion (63.8+/-1.9 vs. 60.9+/-2.4 beats/min, p<0.05). Norepinephrine levels increased from 1.25+/-0.09 to 1.58+/-0.12 nmol/l during insulin infusion and remained unchanged during placebo infusion (1.24+/-0.09 vs. 1.29+/-0.11 pmol/l; p<0.001). Epinephrine levels were also higher during insulin as compared to placebo infusion (249.8+/-17.4 vs. 212.8+/-21.1 pmol/l, p<0.001). The changes did not depend on whether the subject experienced his first or second clamp. Data demonstrate reproducable increasing effects of hyperinsulinemia within the normal physiological range on catecholamine release and systolic BP in healthy humans.

Adolescent↗
PubMed2000

Rhythms of pituitary-adrenal activity during sleep in patients with Cushing's disease.

Previous studies have indicated a dependence of nocturnal pituitary-adrenal secretory activity on central nervous sleep processes in healthy humans: Under normal physiological conditions the release of ACTH/cortisol is inhibited during early sleep and becomes entrained to periods of NonREM sleep during late sleep. Here, we compared nocturnal dynamics in plasma concentrations of ACTH/cortisol in 7 patients with Cushing's disease with those of 7 healthy controls matched in age and sex with the patients. The patients in part were repeatedly tested. The total of 13 nights is composed of 7 nights of hyperpulsatile secretion pattern (5 patients) and 6 nights from hypopulsatile secretion pattern (4 patients). After an adaptation night polysomnographic sleep recordings were obtained and blood was sampled every 15 min between 23.00 and 7.00 h. Controls displayed the typical minimum in ACTH/cortisol concentrations during the early part of the night and maximum concentrations during the late part of the night, whereas ACTH/cortisol levels of Cushing patients indicated a relatively constant elevated pituitary-adrenal activity throughout the night, lacking any circadian variation. Autocorrelation functions revealed the presence of cortisol secretory rhythms with a similar period length in healthy controls (155.6+/-17.4 min) and patients with a hyperpulsatile pattern (142.4+/-6.6 min). In patients displaying hypopulsatility, no significant rhythmicity was observed. However, regardless of the type of secretory pulsatility, adrenal secretory activity started predominantly during periods of NonREM sleep (p<0.01) in healthy controls as well as in patients with Cushing's disease. This data indicates that the normal nocturnal circadian oscillation of pituitary-adrenal activity is absent in Cushing patients, whereas a link between pituitary-adrenal activity and ultradian rhythms of sleep appears to be preserved.

Activity Cycles↗
PubMed2000

Event-related brain potentials and working memory function in healthy humans after single-dose and prolonged intranasal administration of adrenocorticotropin 4-10 and desacetyl-alpha-melanocyte stimulating hormone.

Neuropeptides of the adrenocorticotropin/melanocorticotropin (ACTH/MSH) family are most potent modulators of cognitive function. Their neurobehavioral activity is principally encoded in the 4-10 fragment of the ACTH/MSH molecule; in humans, it has been shown to pertain primarily to functions of attentive stimulus/response processing. The aims of this study were (1) to examine the effects of ACTH 4-10 on event-related brain potentials (ERPs) and behavioral indicators of stimulus encoding within the working memory; (2) to compare the effects after a single dose and after prolonged treatment with ACTH 4-10; and (3) to compare the effects of ACTH 4-10 with those of desacetyl-alpha-MSH (i.e., ACTH 1-13 amide), which, like ACTH 4-10, binds to the known brain melanocortin receptors (MC-Rs) but with distinctly higher affinity. Double-blind, placebo-controlled experiments were performed in 60 healthy control subjects. The authors monitored ERPs and reaction times while these subjects performed an auditory vigilance task ("oddball"). Recall was tested on a verbal short-term memory task including different word categories (neutral, rare, food, sex). After a single (1 mg) as well as prolonged intranasal administration (1 mg/day over a period of 6 weeks), ACTH 4-10 enhanced the positive slow wave in ERPs to target stimuli of the vigilance task (p < 0.05), but left classic P3 unaffected. Moreover, single-dose and prolonged administration of ACTH 4-10 increased the rate of false responses during vigilance (p < 0.01). In the short term, ACTH 4-10 also impaired recall of neutral words (p < 0.05). Equimolar doses of desacetyl-alpha-MSH did not influence ERPs, neither after a single dose nor after prolonged treatment. Similar to ACTH 4-10, desacetyl-alpha-MSH increased the error rate during vigilance and acutely impaired the recall of neutral words. The increase in ERP slow-wave positivity, in conjunction with behavioral impairments after treatment with ACTH 4-10, complemented previous results of inferior focusing of attention and a less concise structure of thought after administration of ACTH 4-10. The changes indicated an impairment in differential processing of relevant versus irrelevant contents within the working memory, and, in this regard, might mimic aspects of psychopathologic disturbances of attention and thought processes. Their persistence after prolonged treatment with ACTH 4-10 suggests an activation of mechanisms subserving the consolidation of the peptide's effects. The poor efficacy of desacetyl-alpha-MSH suggests that the known MC-Rs may be irrelevant for mediating cognitive effects of this neuropeptide family.

Administration, Intranasal↗
PubMed2000

Acute suppression of muscle sympathetic nerve activity by hydrocortisone in humans.

In the present study, we examined the acute influence of hydrocortisone on human sympathetic nerve activity and cardiovascular parameters. Muscle sympathetic nerve activity (MSA), heart rate, and blood pressure were monitored in 8 healthy subjects (20 to 37 years old) before and after a bolus injection of 50 mg hydrocortisone followed by a continuous infusion at 50 mg/h during a period of 3 hours in a placebo-controlled, double-blind, crossover protocol. Recordings were performed at rest and during repeated transient sympathoexcitation induced by voluntary apneas. Resting MSA and endogenous serum cortisol concentrations were also measured in a larger study group (49 experiments, 25 subjects). During the experimental period, MSA burst number increased by 56% from the control level in the placebo group. In contrast, MSA was suppressed by 25% at the end of the hydrocortisone infusion, resulting in a significant treatment effect (P<0.05). In addition, sympathoexcitation during apnea was significantly reduced with hydrocortisone after 180 minutes. In parallel with the sympathetic outflow, blood pressure decreased in the hydrocortisone-treated group, whereas it rose in the placebo group (P<0.05 between groups). No correlation was found between basal MSA and basal cortisol levels. Our results indicate that pharmacological doses of hydrocortisone acutely influence MSA responses to short- and long-lasting environmental stimuli, whereas basal native cortisol levels do not appear to be tonically involved in the regulation of resting MSA. The suppressive hydrocortisone effect is most likely induced via supraspinal autonomic centers and cannot be explained by peripheral steroid mechanisms. The effect of elevated corticosteroid levels on sympathetic nerve discharge may be an important mechanism in cardiovascular adaptations to stress.

Adolescent↗
PubMed2000

Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans.

Circulating plasma insulin and glucose levels are thought to be major regulators of leptin secretion. There is evidence from in vitro and animal experiments that glucose metabolism rather than insulin alone is a main determinant of leptin expression. Here, we tested the hypothesis that in humans also leptin secretion is primarily regulated by glucose uptake and only secondarily by plasma insulin and glucose. In 30 lean and healthy men we induced 4 experimental conditions by using the blood glucose clamp technique. A total of 60 hypoglycemic and euglycemic clamps, lasting 6 h each, were performed. During these clamps insulin was infused at either high (15.0 mU/min x kg) or low (1.5 mU/min x kg) rates, resulting in low-insulin-hypo, high-insulin-hypo, low-insulin-eu, and high-insulin-eu conditions. Serum leptin increased from 0-360 min by 20.5 +/- 4.1% in the low-insulin-hypo, 33.6 +/- 7.6% in the high-insulin-hypo, 39.6 +/- 6.0% in the low-insulin-eu, and 60.4 +/- 7.6% in the high-insulin-eu condition. Multiple regression analysis revealed a significant effect of circulating insulin (low vs. high insulin; P = 0.001) and blood glucose (hypoglycemia vs. euglycemia; P = 0.001) on the rise of serum leptin. However, when the total amount of dextrose infused during the clamp (grams of dextrose per kg BW) was included into the regression model, this variable was significantly related to the changes in serum leptin (P = 0.001), whereas circulating insulin and glucose had no additional effect. These findings in humans support previous in vitro data that leptin secretion is mainly related to glucose metabolism.

Adult↗
PubMed2000

Insulin activation of insulin receptor kinase in erythrocytes is not altered in non-insulin-dependent diabetes and not influenced by hyperglycemia.

Recent studies suggest that high glucose concentrations impair insulin receptor phosphorylation and kinase activation in certain cell models. To examine whether such an effect of glucose can also be demonstrated in vivo, insulin receptor kinase activation was studied in erythrocytes from 11 patients with non-insulin-dependent diabetes (NIDDM), before and after reduction of hyperglycemia (from 14.6+/-1.6 to 6.6+/-0.5 mmol/l fasting plasma glucose within 8.6+/-0.6 days). For the measurement of receptor kinase activation, cells were incubated with insulin (0-400 nmol/l), solubilized and insulin receptors immobilized to microwells coated with anti-insulin receptor antibody. Kinase activity towards insulin receptor substrate-1 and insulin binding were then measured in these wells. Kinase activities (expressed as amol phosphate transferred per min and per fmol insulin binding activity) were similar before (2.4+/-0.4 and 32.2+/-2.0 amol/min per fmol with 0 and 400 nmol/l insulin, respectively) and after improvement of metabolic control (2.4+/-0.5 and 32.0+/-2.3 amol/min per fmol with 0 and 400 nmol/l insulin, respectively). Moreover, activities were also similar in 22 hyperglycemic patients with NIDDM (2.1+/-0.3 and 35.1+/-1.4 amol/min per fmol with 0 and 400 nmol/l insulin, respectively) compared with those in 21 non-diabetic control individuals (2.1+/-0.3 and 34.2+/-1.2 amol/min per fmol with 0 and 400 nmol/l insulin, respectively). We conclude that insulin activation of erythrocyte insulin receptor kinase is not impaired in NIDDM and is not influenced by hyperglycemia.

Blood Glucose↗
PubMed2000

The subcutaneous lipolytic response to regional neural stimulation is reduced in obese women.

Disturbed fat tissue metabolism with a reduction of the lipolytic rate could be an important pathogenetic factor in obesity. Lipolysis of the subcutaneous tissue of the thigh is partly under neural control and can be increased by intraneural stimulation of the lateral cutaneous femoral nerve in lean women. In the present study, we tested whether the lipolytic response to intraneural stimulation is altered in vivo in obese subjects. Seven obese women were examined and the results were compared with those of seven age-matched lean women. After an overnight fast, the lateral cutaneous femoral nerve was intraneurally stimulated for 10 min, and the local subcutaneous lipolytic response to this procedure was evaluated with microdialytic measurements of interstitial glycerol concentrations in the receptive field of the stimulated nerve fascicle. To exclude unspecific effects of stimulation, lipolysis was also controlled in a corresponding area of the contralateral leg. Intraneural stimulation produced no significant change in subcutaneous lipolysis in obese women (25.7 +/- 9.7%, NS). This finding is in sharp contrast with the marked regional lipolytic response in lean women in which the same stimulation procedure enhanced the regional interstitial glycerol levels by 72 +/- 17% (P < 0.05) compared with the unstimulated corresponding area of the contralateral leg. These in vivo results suggest that human obesity is characterized by a profound unresponsiveness of the subcutaneous adipose tissue to neurally stimulated lipolysis. This could be an important factor in the development and treatment of obesity.

Adipose Tissue↗
PubMed2000

Adaptation of cognitive function to hypoglycemia in healthy men.

OBJECTIVE: Antecedent hypoglycemia reduces hypoglycemic counterregulation and symptoms, thereby provoking the hypoglycemia unawareness syndrome. The effects of antecedent hypoglycemia on hypoglycemia-induced cognitive dysfunction are less well established. RESEARCH DESIGN AND METHODS: To determine whether antecedent hypoglycemia also reduces hypoglycemic cognitive dysfunction, we performed stepwise hypoglycemic clamp experiments (4.1, 3.6, 3.1, and 2.6 mmol/l) during a 6-h period in 30 young healthy men. A total of 15 subjects additionally received a 2.5-h antecedent hypoglycemic clamp (3.1 mmol/l) on the preceding day (prior-hypo group), whereas the other 15 subjects did not (control group). Cognitive function was assessed by auditory-evoked brain potentials (AEBPs) and reaction time during a vigilance task and short-term memory recall. Tests were performed during the stepwise hypoglycemic clamp at baseline and at each hypoglycemic plateau. RESULTS: In both groups, performance on all measures of cognitive function deteriorated during stepwise hypoglycemia (all P < 0.01). However, after antecedent hypoglycemia, the hypoglycemia-induced decrease in the amplitude of the P3 of the AEBP was distinctly reduced compared with the control condition (P < 0.05). Also, short-term memory performance was less impaired in the prior-hypo group than in the control group (P < 0.005), and a minor hypoglycemic impairment of reaction time (P < 0.05) was evident in the prior-hypo group. CONCLUSIONS: Data provide evidence that a single episode of mild antecedent hypoglycemia (3.1 mmol/l) attenuates several aspects of cognitive dysfunction during subsequent hypoglycemia 18-24 h later.

Adaptation, Physiological↗
PubMed2000

Selective influence of the menstrual cycle on perception of stimuli with reproductive significance: an event-related potential study.

In this study, we examined changes in the event-related potential (ERP) to stimuli with and without reproductive significance occurring during the menstrual cycle. Eleven spontaneously cycling women were tested during three menstrual phases (menses, ovulatory phase, luteal phase) differing in plasma concentrations of gonadal hormones. ERPs were recorded while subjects were presented with slides showing pictures from four different stimulus categories (sexual stimuli, babies, people occupied with body care, ordinary people). Slides were presented randomly in the context of two tasks, requiring either affective processing (i.e., to judge the emotional content of a slide as positive, neutral, or negative) or structural processing (i.e., to estimate the number of parallel thin lines inserted in each picture). Menstrual phase primarily affected a late positive component (LPC) peaking 550-600 ms poststimulus. The effects were as follows: (i) During the ovulatory phase, amplitude of the LPC to sexual stimuli was larger than that evoked by the other stimulus categories. (ii) This relationship was not apparent during the other menstrual phases or (iii) during the ovulatory phase when the task required structural processing. The ovulatory increase in LPC positivity to sexual stimuli suggests a greater valence of these stimuli during a phase of increased sexual desire. The data indicate a specific effect of the menstrual cycle on the processing of sexual stimuli that increases with deeper emotional processing.

Adult↗
PubMed1999

Intraneural stimulation elicits an increase in subcutaneous interstitial glycerol levels in humans.

1. The effect of intraneural electrical stimulation of the lateral femoral cutaneous nerve on lipolysis in the innervation territory of the stimulated nerve fascicle was studied in seven healthy women. Lipolysis was evaluated by microdialytic measurement of the interstitial glycerol concentration in subcutaneous adipose tissue. 2. Ten minutes of unilateral intraneural stimulation elicited a 22 +/- 8 % (mean +/- s.e.m.) increase in glycerol levels in the stimulated region (P < 0.05), whereas no change was registered in the corresponding area of the contralateral unstimulated leg. 3. Significantly higher glycerol levels in the stimulated vs. contralateral unstimulated region (47 +/- 13 %, P < 0.05) were already observed at baseline (30 min resting period preceding the 10 min stimulation), in all probability as a consequence of the nerve searching procedure and trial stimulations. After the 10 min stimulation, the overall glycerol increase was 72 +/- 17 % compared with the contralateral leg, illustrating the degree of lipolysis induced by the whole experimental procedure. 4. The sympathetic discharge in the lateral femoral nerve (6 recordings) showed typical characteristics of skin sympathetic activity, and the firing pattern was strikingly similar to simultaneously recorded sympathetic discharge in cutaneous nerve fascicles innervating regions without prominent subcutaneous fat stores (2 double nerve recordings). Thus, no component of cutaneous sympathetic outflow specific for the nerve innervating prominent subcutaneous fat stores could be identified. 5. Our findings suggest that sympathetic nerve fibres travelling in cutaneous nerve fascicles exert a regulatory influence on subcutaneous fat tissue in humans. The combination of intraneural recording/stimulation and subcutaneous microdialysis provides a model for evaluating neural control of human fat metabolism.

Adipose Tissue↗
PubMed1999

A determinant factor in the efficacy of GHRH administration in promoting sleep: high peak concentration versus recurrent increasing slopes.

A previous experiment indicated a greater efficacy of episodic than continuous growth hormone (GH)-releasing hormone (GHRH) administration in enhancing sleep. The greater efficacy of episodic administration could principally result from two factors, i.e. the greater peak concentration reached after episodic administration or the recurrence of increasing slopes in GHRH concentration. In order to investigate which factor essentially determines the pharmacodynamics of sleep promotion after GHRH, effects after a transient high peak in GHRH concentration were compared with those of repetitive increases in GHRH concentration. Sleep, plasma concentrations of GH, and GHRH were examined in healthy subjects after evening administration of a 'single' i.v. bolus of 50 micrograms GHRH, after five 'repetitive' boluses of 10 micrograms GHRH, and after placebo. Compared with placebo, single GHRH significantly increased time spent in stage 4 sleep (p < .01) and in stage 2 sleep, reduced time spent in wakefulness and onset latency of stage 4 sleep (p < .05, for each), while repetitive GHRH remained without effects. GH secretory activity also tended to be higher after single than repetitive GHRH. Thus, results suggest the relevance of a transiently high concentration of GHRH in blood as an essential factor in enhancing the central nervous sleep process.

Adult↗
PubMed1999

Sleep and endocrine changes after intranasal administration of growth hormone-releasing hormone in young and aged humans.

Systemic administration of growth hormone-releasing hormone (GHRH) has been found to improve human sleep in previous studies. Here we examined effects of GHRH on endocrine function and sleep after intranasal administration, a method which based on previous studies appears to enable a direct effect of peptides on brain function. Also, it was hypothesized that elderly humans displaying deficient GH release and sleep, benefit from GHRH administration more than young subjects. A study was performed according to a double-blind cross-over design. Each of 12 young and 11 old healthy men were intranasally administered with 300 micrograms GHRH (vs. placebo) 30 min before bedtime at 23:00 h. Sleep was recorded polysomnographically until 07:00 h and blood was collected in 15 min intervals for determination of cortisol and GH. Apart from the well-known age-related changes of hormonal secretion and sleep, intranasal GHRH reduced cortisol nadir concentrations in the beginning of sleep (P < 0.05), and also reduced the sleep-induced elevation in GH concentrations during early sleep. Moreover, results indicated that after intranasal administration GHRH increased rapid-eye-movement (REM) sleep and slow wave sleep (SWS), with this influence concentrating on the second half of sleep time. Effects of GHRH did not depend on the subject's age. We conclude that there is a coordinate influence of intranasal GHRH on the central nervous regulation of sleep processes and of hypothalamic-hypophysiotropic secretory activity in both young and elderly men. The effects may mimic the dual neuronal and endocrine function of hypothalamic GHRH activity.

Administration, Intranasal↗
PubMed1999

EEG complexity and performance measures of creative thinking.

The electroencephalogram (EEG) was used because of its dimensional complexity to establish a differentiation of divergent versus convergent thought, considered fundamental modes of cortical processing. In 28 men, the EEG was recorded while solving tasks of divergent and convergent thinking and during mental relaxation. The EEG during divergent thought was compared between subjects achieving high versus low performance scores on this type of task. The dimensional complexity of the EEG was greater during divergent thinking than during convergent thinking. While solving tasks of divergent thinking, subjects with high performance scores had a lower EEG dimension than did subjects with low scores, in particular over frontal cortical areas. The changes were not reflected in single frequency bands of conventional EEG analysis. Based on Hebb's view of neuron assemblies as functional processing units, the higher EEG complexity during divergent than convergent thinking could be the result of the concurrent activation of a greater number of independently oscillating processing units.

Adult↗