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Biomedical subjects

H L Fehm

Publications and source records attributed to H L Fehm.

At least 181 records · Page 10Linked to original sources

Effects of the neuropeptide PLG (L-prolyl-leucyl-glycinamide) on writing pressure and speed in healthy subjects.

There has been accumulating evidence that PLG influence behavior in humans after peripheral administration. In a randomized double blind study with 10 healthy male subjects in each group, the effect of 25 mg PLG i.v. on writing regulation was investigated and computer evaluated. The writing pressure test was selected as a sensitive parameter to ascertain an effect of PLG on motor behavior. As compared to the placebo group, PLG effects an increase of writing time and a reduction of writing pressure. The results suggested an peptide effect on writing performance in healthy subjects.

Adult↗

Stimulation of the pituitary adrenocortical system in man by cerulein, a cholecystokinin-8-like peptide.

The responses of plasma adrenocorticotropin hormone (ACTH) and cortisol to intravenous injection of cerulein (ceruletide), a decapeptide closely related to cholecystokinin octapeptide, were investigated in healthy men. In response to 16 ng/kg cerulein, plasma ACTH rose from a preinjection level of 42 +/- 11 pg/ml (mean +/- SEM) to a peak level of 81 +/- 16 pg/ml after 15 min. This ACTH increase was followed by a rise in plasma cortisol from a preinjection value of 10.3 +/- 0.9 microgram/dl to a peak value of 17.7 +/- 1.7 microgram/dl after 30 min. This is the first report of the potent stimulating effect of a cholecystokinin-8-related peptide on the pituitary-adrenal system in man.

Adrenal Cortex↗

Dose-dependent influences on electrophysiological signs of attention in humans after neuropeptide ACTH 4-10.

The afferent humoral system exerts significant influences on brain activity. Central nervous actions of the adrenocorticotropic hormone (ACTH) are most likely to be mediated by information coded in a portion of this hormone structure corresponding to ACTH 4-10. Our previous research suggested an impairing effect of ACTH 4-10 on electrophysiological signs of selective attention in humans. The present experiments in 12 male subjects investigated the influences of ACTH 4-10 on different aspects of attention as indicated by auditory event-related potential (AERP) components. Furthermore, dose-response characteristics of these influences should be examined. Attention performance was tested in a dichotic listening paradigm, after 0, 0.1, 1.0, and 10 mg ACTH 4-10, administered intravenously 1 h prior to testing according to a double-blind latin-square design. Different aspects of attention were measured by brain electrical responses evoked either by frequent standard or rare target tone pips, which the subject had to attend to, or to ignore. The selective type of attention was reflected by the Nd determined as mean difference in amplitude between AERPs to tone pips when attended and when unattended, for a latency range between 0-460 ms post-stimulus. In addition, plasma cortisol, heart rate, blood pressure, and behavioral performance were measured. Results indicated a clear reduction of the Nd amplitude after all doses of ACTH 4-10. Other indicators of attention mechanisms such as mismatch processing were not affected by the peptide. The diminished Nd after ACTH 4-10 was due to an increased processing of unattended stimuli, but simultaneously attended tones were processed less intensively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Influences of ACTH 4-10 on event-related potentials reflecting attention in man.

The present paper is concerned with effects of the 4-10 sequence of the endogenous ACTH on electrophysiological measures of attention in humans. It was attempted to replicate previous findings of an impaired selective attention following administration of an analog of ACTH 4-9. The effect of this analog had been found to dominate in the beginning of the blocks of an attention task, but to fade away with time on task. In the present study, fourteen male students were tested in a dichotic listening paradigm, 40 min after intranasal application of either 0.4 mg ACTH 4-10, or placebo. Averaged auditory evoked potentials (AEPs) to attended and inattended tone pips, EEG power spectra, heart rate and blood pressure, and behavioral performance were measured during task performance. ACTH 4-10 appeared to slightly impair selective attention as indicated by AEP responses. In particular, the positive shift of the AEP waveforms to inattended stimuli was reduced at the beginning of each block of tone pips under ACTH 4-10. The pattern of actions resembled the effects observed after administration of the more potent synthetic analog of ACTH 4-9 in the previous experiment. Effects of ACTH 4-10 on the AEPs to inattended stimuli, however, differed from influences of the synthetic analog in that they did not affect a rather wide latency range but concentrated on the latency range of the P200 component.

Adolescent↗

Differential effects of hydrocortisone, fluocortolone, and aldosterone on nocturnal sleep in humans.

Previous experiments have suggested that sleep processes are sensitive to influences of corticosteroids. The present experiment was designed to compare effects of three different corticosteroids on human sleep: fluocortolone (a synthetic pure glucocorticoid), cortisol which possesses glucocorticoid and mineralocorticoid activity, and aldosterone (the major mineralocorticoid). Ten male adult subjects were tested in four experimental nights according to a double-blind latin-square design under conditions of either 1.0 mg of aldosterone, 20 mg of fluocortolone, 80 mg of hydrocortisone, or placebo. Substances were administered orally (fluocortolone, 23.00 h) or infused iv throughout the night (hydrocortisone, aldosterone) starting at 23.00 h. Hydrocortisone and fluocortolone induced a substantial reduction of rapid eye movement sleep. Hydrocortisone increased slow wave sleep activity. No such effect was observed after fluocortolone. Effects on sleep processes of aldosterone, in general, seemed to be neglegible. The results demonstrate differential effects of synthetic glucocorticoid, cortisol, and aldosterone on sleep in humans, which may be attributed to the heterogeneity of corticosteroid receptors in the brain.

Administration, Oral↗

Effects of corticotropin releasing hormone on human brain function: an analysis based on auditory evoked potentials.

There is evidence that the peptides derived from proopiomelanocortin as well as the neurohypophyseal hormones exert important and substantial effects on brain functions after intracerebroventricular and peripheral administration. This led us to study the effects of intravenous hCRH on brain functions in humans using electroencephalographic techniques. In our experience the event-related potentials (e.g. auditory evoked potentials) provide a sensitive and accurate assay systems to study such effects of peptides. Male volunteers were tested in a dichotic listening paradigm, providing electrophysiological measures of selective attention. Human CRH (50 micrograms/hr i.v.) augmented selective attention as indicated by an increased difference between evoked potential waveforms to attended and to unattended stimuli. The opposite results, a decrease in selective attention, was observed after treatment with the behavioral active fragment of adrenocorticotropin, ACTH 4-10. In comparison to ACTH 4-10, lysine-vasopressin, and cortisol, CRH displayed a unique pattern of influences on event related potentials. From these results we conclude that CRH can affect brain function in man and does so by a direct action on the brain and not only by stimulating the release of other behavioral active hormones.

Adrenocorticotropic Hormone↗

Night-time plasma cortisol secretion is associated with specific sleep stages.

Polysomnographic recordings were obtained in 16 healthy male subjects in order to evaluate temporal interrelationships between concentrations of plasma cortisol and sleep at night. The pattern of nocturnal cortisol secretion appeared to be synchronized with the periodicity of sleep: rapid eye movement (REM) sleep was found to be primarily present when cortisol concentrations were decreasing, indicating a diminished or absent secretory activity of the adrenals at that time; wakefulness and Stage 1 sleep, by contrast, were associated with increasing plasma cortisol concentrations. Furthermore, the enhanced adrenal secretory activity usually preceded the occurrence of light sleep or wakefulness, which is in accord with a wakening effect of plasma cortisol. Just prior to the onset of the first pronounced rise in plasma cortisol during sleep, episodes of slow wave sleep (SWS) became more frequent. This suggests that the offset of episodes of SWS may act as a trigger for the first pronounced nocturnal rise in plasma cortisol.

Adrenal Cortex↗

Acute effects of desipramine and clomipramine on pituitary-adrenal axis in man.

Brain neurotransmitters play an essential role in central regulation of hypothalamic factors which stimulate or inhibit the secretion of pituitary hormones. Insight in this complex system might be obtained by analysing changes in pituitary and peripheral hormone secretion following the administration of neuroactive drugs which influence the action of neurotransmitters. Desipramine is well-known to inhibit presynaptic norepinephrine reuptake, clomipramine on the other hand interferes with the serotoninergic system. In 15 male volunteers, the effects of single-dose administration of each drug were studied in comparison to placebo. Basal concentrations of ACTH and cortisol, as well as the rise of both hormones following insulin-induced hypoglycemia, were studied. Basal cortisol values and the response to hypoglycemia were not affected by either pharmacon in this study. Slight differences could be seen in the ACTH responses, which were however not significant.

Adrenocorticotropic Hormone↗

ACTH and attention in humans: a review.

In addition to the hormonal action of corticotropin (ACTH) on the adrenal cortex, this peptide and fragments of it may function as chemical signals in CNS synapses. This report reviews studies on behavioral and psychophysiological effects of ACTH-related neuropeptides. Experiments will be emphasized which applied EEG techniques for the measurement of peptide-induced changes on aspects of information processing in man. It is proposed to conceptualize the pattern of actions of ACTH-related neuropeptides as a blocking of suppressive functions occurring, for example, during habituation or selective attention. Disinhibitory effects mediated by structures of the limbic system may be responsible for repeatedly observed improvements of sustained attention, but impairments of selective attention following the administration of ACTH-related neuropeptides. Under the influence of these peptides the attention is more easily attracted by stimuli, irrespective of their relevance.

Adrenocorticotropic Hormone↗

Influences of corticosteroids, dexamethasone and hydrocortisone on sleep in humans.

The present two experiments were designed to investigate the effects of a synthetic and of a natural corticosteroid on nocturnal sleep in humans. Both experiments were held double-blind and designed according to a within-subject cross-over comparison. In the first experiment, 1 mg of dexamethasone applied orally prior to sleep (11.00 p.m.) led to a reduction of the percent of time spent in REM and in stage 4 sleep. The amount of stage 2 sleep tended to be increased after dexamethasone. In the second experiment, an infusion of 100 mg hydrocortisone throughout the night also reduced REM, but increased stage 4 sleep. A statistical comparison of both experiments suggested that both steroids not only reduced REM sleep but also tended to enhance intermittent wakefulness. This analysis also confirmed opposite effects on measures of slow-wave sleep of both substances. The results represent a first demonstration of differential effects of synthetic and natural corticosteroids on sleep, which has to be substantiated in further studies directly comparing effects of these steroids.

Adult↗

Relationships between sleep stages and plasma cortisol: a single case study.

The relationship between the plasma cortisol level and sleep stages was investigated in a single male subject across 17 nights. Blood samples were taken every 30 min from 11.00 p.m. until 02.30 a.m. and every 15 min during the rest of the night. Data analyses performed for the whole nights did not give evidence for strong relations between plasma cortisol and sleep stages. Analyses on data of the second part of the night, beginning with the onset of the first cortisol peak, revealed that plasma cortisol was primarily decreasing when rapid eye movement sleep (REM) was present. Sleep stage I and periods of wakefulness were associated with increasing cortisol levels. There was no evidence for a particular EEG event triggering the first rise of plasma cortisol during the night.

Adult↗

[Global pituitary stimulation test with releasing hormones].

The endocrine function of the thyroid and gonads has for long been investigated using the corresponding releasing hormones (TRH- and LHRH-test, respectively). The adrenal cortex has, up to now, been stimulated using insulin-induced hypoglycaemia or lysine-vasopressin and growth hormone stimulated using arginine. New diagnostic possibilities have arisen with the isolation of the corresponding releasing-hormones, CRF and GRF, and with the availability of these too for clinical use. Using the four above mentioned releasing-hormones in a global pituitary-stimulation-test, the secretion of ACTH, cortisol, STH, TSH, LH, FSH and prolactin hormones can now be examined together.

Adrenocorticotropic Hormone↗