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Biomedical subjects

H L Fehm

Publications and source records attributed to H L Fehm.

At least 163 records · Page 9Linked to original sources
PubMed1990

Time course of ACTH 4-10 effects on human attention.

Previous studies have demonstrated that the adrenocorticotropic hormone (ACTH) and its 4-10 fragment are potent modulators of attention in humans. In these studies the Nd component ('negative displacement') of the stimulus-evoked brain potential (event-related potential, ERP), which is a neurophysiological indicator of selective attention, proved most sensitive to effects of these peptides. The Nd decreased in amplitude linearly with logarithmically increasing doses of ACTH 4-10 applied. Here we report results complementing these previous findings by establishing a time course of the effects of ACTH 4-10 on human attention. In a double-blind cross-over study, attention performance on a dichotic listening task was tested in 18 healthy volunteers, after having received intravenously either placebo or 1 mg ACTH 4-10. Tests took place 0, 30, 90, 180, 330, 600 min, 24, 48 and 72 h after drug intake and took about 15 min. Each subject was tested on 4 of these occasions, selected according to a random schedule. During task performance ERPs to the different task stimuli were recorded. ERPs were used to determine the Nd (an indicator of controlled processing of stimuli which the subjects selectively attended to) and the mismatch negativity (MMN) reflecting automatic processing of stimulus deviance. ACTH 4-10 diminished the Nd significantly at 30 min after treatment administration. On none of the other occasions significant changes in Nd occurred. MMN was not affected by the peptide. The results indicate a short-term action of ACTH 4-10 on selective attention, which takes about 30 min to develop and does not last longer than 90 min after treatment.

Adrenocorticotropic Hormone↗
PubMed1990

Differential effects of human and pork insulin-induced hypoglycemia on neuronal functions in humans.

Insulin has been found to cross the blood-brain barrier, and insulin receptors have been detected in different structures of the brain. However, the biological significance of insulin acting in the brain remains unclear. Reports of differential awareness of hypoglycemic symptoms during human insulin (HI)- and pork insulin (PI)-induced hypoglycemia hint at a modulatory influence of insulin on sensory processing. In a double-blind study, we recorded auditory-evoked potentials (AEPs), indexing neuronal transmission along sensory pathways, in 30 healthy male subjects during a baseline condition and HI- and PI-induced mild hypoglycemia of 2.65 mM. Fifteen subjects were tested after 20 min and another 15 after 50 min of constant hypoglycemia. During hypoglycemia, subjects had to indicate the severity of hypoglycemic symptoms and their current mood. Hypoglycemia increased latencies of the P3 component and reduced amplitudes of the N1, P2, and P3 components. Despite identical blood glucose and serum insulin levels in both sessions, effects of PI-induced hypoglycemia on AEP components were significantly stronger than those of HI-induced hypoglycemia (P less than 0.05). Differences between the effects of the insulins were consistently apparent after 20 min of hypoglycemia, indicating a short-term action of these hormones on central nervous system functions. Also, after 20 min, but not after 50 min, of steady-state hypoglycemia, subjects felt more excited during PI than HI infusion (P less than 0.05). The results indicate different influences of HI and PI on sensory function during hypoglycemia. These differences, occurring during early hypoglycemia, could contribute to the differential awareness of hypoglycemic warning symptoms during HI- and PI-induced hypoglycemia in diabetic patients.

Animals↗
PubMed1990

Different effects of human and porcine insulin on hypoglycemia-induced abnormalities of brainstem sensory function.

Following a switch from porcine insulin (PI) to human insulin (HI), a subgroup of diabetic patients complained of unawareness of hypoglycemia. In the present study, a glucose clamp technique was used to assess changes in auditory evoked brainstem responses (ABR) during infusion of HI and PI (0.015 IU/kg/min) under conditions of euglycemia (about 5.00 mM) and of hypoglycemia (3.40 and 2.60 mM) in 9 healthy volunteers. Serum insulin and plasma glucose did not differ between HI and PI conditions. ABR components remained unchanged during the euglycemic clamp, but increased in latency during hypoglycemia in all subjects. At mean glucose levels of 2.60 mM, the increase in latency of ABR wave V ranged between 50 and 400 microseconds during PI infusion, and between 100 and 2,460 microseconds during HI infusion. Thus, compared to the PI condition, changes during HI infusion were significantly more variable (p less than 0.01) due to some subjects displaying extremely prolonged ABR latencies. These findings suggest that hypoglycemia induced by HI can be more detrimental to early sensory processing in humans as compared to PI.

Adult↗
PubMed1989

Fragments of ACTH affect electrophysiological signs of controlled stimulus processing in humans.

It has been proposed that the systemic administration of the 4-10 fragment of ACTH in humans affects primarily attention. In the present study, influences of ACTH 4-10 on event-related potential (ERP) indicators of attention were evaluated in healthy men. The influences were compared with those of an analog of the ACTH 4-9 sequence (HOE 427) which was expected to have an increased potency. Following an adaptation session, each of 20 healthy men was tested on four occasions in a double-blind study designed according to a latin-square. On each occasion, subjects received (iv) one of the following treatments: placebo, ACTH 4-10 (1 mg), HOE 427 (60 micrograms) and HOE 427 (200 micrograms). Treatments were administered 40 min prior to recordings of ERPs. ERPs were recorded while the subjects performed on a dichotic listening task paradigm. The various tone pips presented in this task elicit ERPs providing measures of controlled stimulus processing (Nd reflecting selectivity of attention, and P3) and automatic processing of stimulus deviance (mismatch negativity). ACTH 4-10 as well as 200 micrograms HOE 427 reduced Nd and also P3 amplitudes following attended stimuli. Smaller (non-significant) changes in the same direction were observed following 60 micrograms HOE 427. The results suggest an impairing influence of ACTH 4-10 and of HOE 427 on signs of controlled stimulus processing, particularly on the Nd. The analog appeared to be more potent than the endogenous 4-10 fragment.

Adrenocorticotropic Hormone↗
PubMed1989

Effects of cholecystokinin and calcitonin on evoked brain potentials and satiety in man.

Central nervous effects of the peptides cholecystokinin (CCK) and calcitonin (CT) were tested in an attention task for their effects on Auditory Event Related Potentials (AERPs) and for their effects on satiety and activation as measured in self-rating scales. Thirteen healthy subjects received either 3 IDU/kg bodyweight CCK 1-33, 0.1 IU/kg bodyweight CT and placebo according to a double-blind within-subject cross-over design. Subjects had fasted for at least 16 hr prior to the experiment. CCK induced the feeling of satiety after stimulation with the preparation of a meal. The peptides prevented an attenuation of the N2-component of the AERP after the preparation of a meal, indicating that the subjects were less distracted by the food cues. The results suggest that the central nervous effects of CCK and CT may constitute an aspect of satiated behavior.

Adult↗
PubMed1989

The influence of a vasopressin-analogue (DGAVP) on event-related potentials in a stimulus-mismatch paradigm.

To assess the influence of DGAVP (des-glycinamide-arginine-8-vasopressin, a synthetic vasopressin analogue) on the processing of stimuli and stimulus deviance in humans in a double-blind cross-over experiment, 13 subjects received 60 IU DGAVP versus placebo intranasally 48, 24, and 1 h prior to the experimental session. Auditory event-related potentials (ERPs) were taken as a tool to investigate central nervous processing in an experimental task that required the subjects to count different kinds of rare tone pips deviating in pitch and probability compared to frequent standard tones. Direction of attention was manipulated by instructing the subject to count a different class of deviating tone pips in each attention condition. DGAVP enhanced the N2 of the ERP to tone pips deviating extremely in pitch from standard tones, whether or not the extremely deviating pips were to be attended to by the subjects. This influence suggests an intensified mismatch processing under DGAVP that may result from a general excitatory effect of this substance on cortical activity.

Administration, Intranasal↗
PubMed1989

Taste thresholds in man are differentially influenced by hydrocortisone and dexamethasone.

The present study focused on sensory processing (taste threshold) in healthy young men given different cortisol doses within the normal physiological range. It aimed to differentiate the effects of dexamethasone, a synthetic pure glucocorticoid, compared to hydrocortisone, which has both glucocorticoid and mineralocorticoid properties. In a double-blind, cross-over design, 18 male subjects participated in three sessions. Subjects were pretreated orally with hydrocortisone (50 mg), dexamethasone (2 mg) or placebo. Taste detection was tested by a forced-choice three stimulus drop technique to determine detection acuity and a signal detection procedure to determine the ability to detect differences in NaCl concentration. Cortisol concentrations were determined in blood and saliva. Hydrocortisone and dexamethasone had opposite effects on taste detection acuity. With the highest cortisol levels after intake of hydrocortisone, subjects made more errors in detection trials with respect to stimuli close to the absolute taste detection threshold than after intake of dexamethasone. Detection of differences was impaired by both glucocorticoids. This type of behavioral study in man may help clarify the roles of heterogeneous corticosteroid receptor systems within the human brain.

Adolescent↗
PubMed1989

Cortisol deficiency in metomidate anesthetized bacteremic pigs: results in circulatory failure--beneficial effect of cortisol substitution.

Etomidate and the closely related metomidate are known to inhibit cortisol synthesis. We studied the influence of metomidate on hemodynamic performance and survival time of bacteremic pigs. Thirty pigs, 30.2 +/- 0.8 kg, were anesthetized with intravenous metomidate (2.5 mg.kg-1.h-1) plus ketamine (3.0 mg.kg-1.h-1), and were then mechanically ventilated. The animals were randomly allocated to three groups of 10 pigs each. Group A received an infusion of live Pseudomonas aeruginosa bacteria (2.5.10(9).kg-1.h-1 organisms until death), Group B additionally received a bolus of 1 mg.kg-1 cortisol (followed by an infusion of 0.1 mg.kg-1.h-1) starting 1 h prior to the bacterial infusion, and Group C served as anesthesia control without receiving bacteria or cortisol. The experiments in Group C were terminated after 10 h. In Group A the cortisol level was severely suppressed from the very beginning. The animals died of circulatory failure after 4.3 +/- 0.4 h. In contrast, Group B exhibited fairly stable hemodynamics, but the animals died due to pulmonary edema after 11.1 +/- 1.3 h. Cortisol deficiency in metomidate anesthetized pigs facilitates the development of circulatory failure in the course of Pseudomonas bacteremia, which does not occur if cortisol is infused to reconstitute a physiological level. However, this cortisol substitution did not prevent the development of pulmonary edema caused by Pseudomonas aeruginosa. Possible mechanisms of the deleterious effect of cortisol deficiency and implications in regard to the clinical use of metomidate/etomidate are discussed.

Anesthesia, Intravenous↗
PubMed1989

Influences of cortisol on auditory evoked potentials (AEPs) and mood in humans.

The present study was designed to investigate effects of cortisol on evoked potential indicators of sensory processing and on mood in 45 healthy human subjects. In order to determine the glucocorticoid effect to be primary excitatory or inhibitory, the vertex potential components. (P1, N1, P2) of the auditory evoked potential (AEP) were assessed, which also indicate a stimulus-induced cortical arousal response mediated by the nonspecific sensory system of the reticular formation. The AEPs were recorded while the subject performed a vigilance task containing 8 blocks of monotonous series of tone pips presented at different interstimulus intervals. Mood was assessed by an extensive adjective checklist. Experiments were held double-blind and designed as between-group comparison. Subjects received either 40 or 20 mg hydrocortisone (constantly infused between 35 min prior to testing till the end of the experiment), or placebo. Enhanced plasma cortisol levels were related to increased amplitudes of the AEP vertex response. Furthermore, cortisol augmented self-reported concentration and reduced tiredness during task performance. The glucocorticoid effects on both AEPs and self-report measures suggest an excitatory influence of cortisol on brainstem and thalamic mechanisms mediating the stimulus-induced cortical arousal.

Adolescent↗
PubMed1989

Influences of corticotropin-releasing hormone, adrenocorticotropin, and cortisol on sleep in normal man.

We studied the effects of the hormones of the hypothalamus-pituitary-adrenocortical axis on sleep processes in normal men. In one experiment, 10 men received placebo, cortisol (6 mg/h), and ACTH (0.55 U/h) as continuous iv infusions from 2200-0700 h on 3 separate nights. In another experiment, placebo and CRH (30 micrograms/h) were administered to another 10 men in the same manner. The mean plasma cortisol levels were comparable during the cortisol and ACTH infusions (552 vs. 668 nmol/L). During both infusions, the time spent in rapid eye movement (REM) sleep was significantly (P less than 0.01) reduced compared to that during the placebo infusion, and the cortisol infusion significantly (P less than 0.05) enhanced the time spent in slow wave sleep (SWS). The CRH dose used only moderately increased plasma ACTH and cortisol levels; the changes in SWS and REM sleep during CRH infusion were in the same direction as occurred during the cortisol infusion, but were not significant. These results suggest that cortisol has a sleep modulatory effect. The decrease in REM sleep during the ACTH infusion may be mediated by the rise in endogenous cortisol. However, ACTH specifically altered sleep, in that it inhibited the cortisol-induced increase in SWS. Peripherally administered CRH had no intrinsic influence on sleep.

Adrenocorticotropic Hormone↗
PubMed1989

Neurophysiological effects of recombinant interferon-gamma and -alpha in man.

Treatment of malignant tumors with interferon (IFN) is in some patients accompanied by serious neurological side effects. The present study assessed neurophysiological changes in spontaneous EEG activity, visual-evoked cortical potentials (VEPs), and brainstem auditory-evoked potentials (BAEPs) during IFN-gamma or IFN-alpha therapy in 9 patients. In addition, blood pressure, heart rate and body temperature were monitored. In all sessions under IFN, the latency of the P100 component of the VEP was shortened as compared to baseline conditions. IFN also reduced latencies of BAEP components, and diminished amplitudes of the spontaneous EEG activity within the alpha and beta frequency band. These latter effects were somewhat less consistent than those on VEPs. The major neurophysiological changes appeared to be similar for IFN-gamma and IFN-alpha. The results are in accord with an excitatory effect of IFN on central nervous activity. The magnitude of changes excludes a neurotoxicity of IFN-gamma or IFN-alpha at the doses used in this study.

Adult↗
PubMed1988

Vasopressin but not oxytocin enhances cortical arousal: an integrative hypothesis on behavioral effects of neurohypophyseal hormones.

Behavioral changes after administration of the neurohypophyseal hormones vasopressin and oxytocin can be observed in animal and man. Several groups attempted to specify these changes in terms of memory or attention processing enhancement for vasopressin and amnesic properties for oxytocin. These interpretations, however, were targets for recent criticism. In a double-blind between-subject comparison with male volunteers receiving arginine-vasopressin (AVP), oxytocin or placebo intranasally prior to the experimental session, we tried to develop an alternative hypothesis on the basis of behavioral and EEG measures. At the beginning of the session subjects had to learn a list of 25 unrelated nouns within five trials. Recall was assessed 1 h later. Neither learning nor long-term recall were affected by peptide treatments. In a second vigilance task subjects had to covertly count eight series of tone pips. Averaged auditory evoked potentials to these tones showed the expected habituation during the course of the task within all three groups. Vasopressin-treated subjects, however, displayed significantly higher amplitudes of the vertex potential as compared to the other treatment groups. AVP effects were most prominent with the longest interstimulus interval. No influences on heart rate or blood pressure were found. Results indicate that vasopressin induces an enhancement of stimulus-related phasic cortical arousal, and that in this respect oxytocin has no effect.

Adult↗
PubMed1988

The behaviorally active peptide ACTH 4-10: measurement in plasma and pharmacokinetics in man.

A specific radioimmunoassay for the quantitative measurement of ACTH 4-10 and a procedure for its extraction from plasma have been developed. Its pharmacokinetics was studied in eight healthy male volunteers given ACTH 4-10 125 micrograms/kg body weight as a bolus i.v. injection, by infusion and intranasally. Following the i.v. bolus, plasma levels rapidly declined biexponentially, with half-lives of 0.39 +/- 0.05 min for the alpha-phase and 3.84 +/- 1.5 min for the beta-phase (mean +/- SD). The constant rate i.v. infusion yielded steady-state levels between 0.74 and 5.06 ng/ml plasma. Administered as intranasal spray, absorption of intact ACTH 4-10 was low and variable (maximal bioavailability 7.6%). The results are discussed in relation to the dose-dependent effects of ACTH 4-10 on the auditory evoked potential.

Administration, Intranasal↗
PubMed1988

Combined pituitary stimulation test: interactions of hypothalamic releasing hormones in man.

The use of hypothalamic releasing hormones for the clinical assessment of anterior pituitary function is both simple and free of severe side effects. Tests with the recently discovered substances GRF and CRF as well as with combinations of several releasing hormones are therefore used in many clinics. A reliable interpretation of such combined tests, however, is only possible when positive or negative interactions between these releasing hormones are known. After a rest of 2 h to reach basal cortisol levels, 7 groups of 5 male volunteers each received an iv bolus injection consisting of either: A): GRF (100 micrograms) + CRF (50 micrograms) + TRH (200 micrograms) + LHRH (100 micrograms), B): CRF + TRH, C): GRF + TRH, D): LHRH + TRH, E): TRH, F): GRF, G): CRF. During the following 2 h, GH, TSH, cortisol, LH, FSH and prolactin were measured every 15 min. The TSH response after the injection of all 4 releasing hormones was significantly higher (delta TSH = 16.5 +/- 2.0 microU/ml, x +/- SE) compared to the injection of TRH alone (delta TSH = 9.3 +/- 1.4 microU/ml; p less than 0.025). This increment in TSH secretion was confirmed when 2 groups of 5 female volunteers were studied with the TRH-test (delta TSH = 9.9 +/- 1.8 microU/ml) or the combination of all four releasing hormones (delta TSH = 16.8 +/- 2.9 microU/ml; p less than 0.05). This exaggerated TSH-response to TRH was demonstrated to be entirely due to simultaneous administration of GRF, whereas CRF and LHRH in combination with TRH had no additional effect on TSH release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Influences of partial REM sleep deprivation and awakenings on nocturnal cortisol release.

Decreasing endogenous plasma cortisol levels during rapid eye movement (REM) sleep have been recently reported, suggesting a diminished or absent secretory activity of the adrenals during this period. On the other hand, episodes of light sleep (Stage 1) and intermittent wakefulness have been found to be associated with increasing plasma cortisol levels. The present experiments in 10 adult men were designed to examine whether or not REM sleep inhibits adrenocortical activity and if short periods of wakefulness increase nocturnal cortisol release. Somnopolygraphic recordings were obtained from each subject under three experimental sleep conditions: a baseline night, an REM deprivation night in which the subject's sleep was disturbed contingent upon the occurrence of REM, and a control night in which sleep was disturbed both during REM deprivation and non-REM (NREM) epochs, i.e., mostly during Stage 2 sleep. This last condition was introduced to distinguish the effects of REM deprivation from those of arousals that may per se act as stressful stimuli for cortisol release. Contrary to expectation, we found that both REM sleep deprivation and arousals in NREM epochs reduced rather than enhanced mean plasma cortisol levels as compared with baseline conditions. These findings do not support the hypothesis of an inhibitory effect of REM sleep on cortisol secretion, though present data do not refute this hypothesis. The awakenings, or the light sleep subsequent to sleep disturbance, appear to have no stimulatory effect on adrenocortical secretion. Awakenings during sleep at night may even reflect the activity of mechanisms inhibiting sleep-related increases in plasma cortisol concentration.

Adult↗
PubMed1988

Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin.

Cortisol secretion by the adrenal cortex is thought to depend upon a preceding release of pituitary ACTH. This concept ignores a large number of observations suggesting important extrapituitary influences on adrenocortical function. The present study was designed to demonstrate the contribution of these extrapituitary mechanisms in the release of cortisol induced by human corticotropin releasing hormone (hCRH) in man. In patients with proven deficiency in pituitary ACTH the functional atrophy of the adrenals had been restored by pretreatment with long-acting ACTH. Fifty-eight hours after the second and last injection of ACTH a CRH test was performed (100 micrograms hCRH intravenously). Administration of hCRH induced a small but significant increase in plasma cortisol. Surprisingly, this rise was preceded by an increase in plasma ACTH similar to the ACTH response observed in the control group. It appeared that hCRH is able to stimulate cortisol release in the absence of pituitary ACTH, presumably by stimulating extrapituitary sources of ACTH.

Adenoma↗
PubMed1988

The significance of sleep onset and slow wave sleep for nocturnal release of growth hormone (GH) and cortisol.

The present experiments were designed to compare the influences of delayed sleep onset and temporary slow wave sleep (SWS) deprivation on nocturnal GH and cortisol release in humans. Polysomnographic recordings and blood samples were obtained from 10 male subjects each participating on three experimental nights. On all nights the subjects went to bed at 2300 h and were wakened at 0700 h. On the baseline night, the lights were turned off at 2300 h, enabling the subject to fall asleep. To delay sleep onset, on the second night, the subjects were kept awake until 0200 h. On the third night, the subjects were deprived of SWS between 2300 h and 0200 h. SWS deprivation was accomplished by sounding a tone as soon as it appeared the subject was going into stage 3 sleep. The order of experimental conditions was randomized. On the baseline nights, the occurrence of SWS was closely associated with the occurrence of GH secretory bursts, and plasma cortisol concentrations were low at that time. Delaying sleep onset after 0200 h substantially delayed the GH secretory bursts, which again coincided with the initial periods of SWS. Deprivation of SWS between 2300 h and 0200 h did not significantly reduce the time spent in SWS, because it recovered after the deprivation was discontinued. On these nights, the GH secretory peaks were not significantly changed in amplitude. However, they were dissociated from SWS, because they occurred mostly subsequent to sleep onset rather than during the main epochs of SWS occurring after 0200 h. Nocturnal cortisol release was distinctly delayed with delayed sleep onset, whereas temporary SWS suppression had no significant effect. Thus, the timing of both nocturnal GH and cortisol secretion seems more dependent on sleep onset than on SWS.

Adolescent↗