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Biomedical subjects

H L Fehm

Publications and source records attributed to H L Fehm.

At least 199 records · Page 11Linked to original sources

An ACTH 4-9 analog impairs selective attention in man.

Male adults were tested in a dichotic listening task, providing electrophysiological measures of selective attention. Subjects were tested twice, 60 min after oral administration of either 40 mg of ACTH 4-9 analog, or placebo. Averaged auditory evoked potentials (AEPs) to tone pips when attended and when unattended, EEG spectra, heart rate and blood pressure, and behavioral performance were measured during task performance. ACTH 4-9 analog treatment impaired selective attention as indicated a) by a diminished difference between evoked potential waveforms to attended and to unattended tone pips, b) by an impaired behavioral signal detection performance. Furthermore, frontal EEG theta activity slowed down after ACTH 4-9 analog. With time on task, however, there was no decay, but an improvement of selective attention after peptide administration. Differences in attention could not be due to concurrent changes in general cortical and autonomic arousal as indicated by EEG alpha activity, blood pressure and heart rate. Since separate analyses of the AEPs revealed an increased processing of the unattended tone pips in the ACTH 4-9 analog sessions the impaired selective attention under ACTH 4-9 analog may be described as an inability to suppress processing of irrelevant or distracting stimuli.

Adolescent↗

Effects of an ACTH 4-9 analog on auditory evoked brainstem responses and middle latency responses.

Early and middle latency auditory evoked potentials (EAEPs and MAEPs) were recorded from thirteen male volunteers after oral administration of either 40 mg of an ACTH 4-9 analog (ORG 2766) or placebo. Main results indicate slightly longer latencies of the later components of the EAEPs after ACTH 4-9 analog. Effects of differences in treatment were clearest with very high stimulus rates. Therefore, these effects do not lend themselves for the explanation of ACTH 4-9 analog-induced changes in long latency auditory evoked potentials of cortical origin obtained with comparatively slow stimulus rates in earlier studies. In addition, the ACTH 4-9 analog inhibited a decrease in amplitudes of the Na component of the MAEP across the session. This latter result may be in line with dishabituating actions of the peptide.

Adolescent↗

Disturbed cortisol secretion in man: contrasting Cushing's disease and endogenous depression.

A disturbed regulation of cortisol secretion is the principal pathology of Cushing's disease and is also the most widely reported neuroendocrine dysfunction in endogenous depression. Because additional clinical signs in both diseases indicated a hypothetical common pathway, we examined 17 patients suffering from Cushing's disease, following a protocol identical to that used in depressed patients (e.g., Hamilton Rating Scale for Depression, self-rating scales, and a clinical interview). Affective disorders, frequently observed in patients with Cushing's disease, were undetectable after surgical treatment (adrenalectomy or microadenomectomy of hypercortisolism). This was an unexpected result, since we found that recovered patients were still characterized by a disturbance of glucocorticoid feedback regulation, probably acting at the hypothalamic level. Our results, as well as numerous reports from others, failed to support the hypothesis that an impaired regulation of cortisol is directly linked to depressive illness.

Adolescent↗

Cyclic Cushing's syndrome combined with cortisol suppressible, dexamethasone non-suppressible ACTH secretion: a new variant of Cushing's syndrome.

A 55 year old woman with an unusual form of Cushing's disease was studied. During several periods (periods lasting up to 84 days) evidence of cortisol hypersecretion with cycles occurring every 6 days was found. Suppression of plasma cortisol through orally administered dexamethasone (up to 32 mg per day) could not be achieved either during periods of cyclic cortisol hypersecretion or during apparent remission with normal cortisol secretion. Marked suppression of plasma ACTH was measured in response to an iv infusion of 50 mg cortisol over a period of 55 min whereas a similar test with 2 mg dexamethasone (iv bolus) did not suppress ACTH secretion. Transsphenoidal exploration of the sella revealed a tumour surrounding the anterior pituitary. Examination of the pituitary showed a few tiny tumour structures embedded in normal tissue which could not be removed, when the tumour was resected selectively under preservation of normal appearing tissue. Post-operatively, clinical and chemical remission (normal response to 1 mg dexamethasone) was observed for about 4 months. Thereafter, cortisol hypersecretion occurred again necessitating bilateral adrenalectomy. Our results are compatible with the assumption that normal hypothalamic-pituitary-adrenal suppressibility with cortisol, but not with dexamethasone, was caused by the loss of feedback receptors for dexamethasone in the presence of cortisol receptors in the cells which secrete ACTH or CRF. The combination of cyclic hypercortisolism with dexamethasone non-suppressible Cushing's syndrome has not been reported before and thus represents a new variant of Cushing's syndrome.

Adrenocorticotropic Hormone↗

Evidence for ACTH-unrelated mechanisms in the regulation of cortisol secretion in man.

In an attempt to elucidate the significance of ACTH independent mechanisms in the regulation of cortisol secretion in man, the dynamics of plasma ACTH and cortisol levels were studied in response to different stimuli. The cortisol response to small amounts of exogenous ACTH and to insulin induced hypoglycemia was preceded by an increase in ACTH levels appropriate to explain the increase in cortisol. In contrast, after administration of methamphetamine, there was an increase in cortisol levels in the absence of any changes in ACTH concentrations. Apparently, the methamphetamine induced cortisol secretion was not mediated by radioimmunoassayable ACTH. A diurnal rhythm was observed for the responses to hypoglycemia and to methamphetamine with larger cortisol responses in the evening as compared to the forenoon. These changes were not accompanied by parallel changes in the ACTH responses. From these differences, additional evidence is provided for the importance of ACTH independent mechanisms in the regulation of cortisol secretion.

Adrenal Cortex↗

Human memory and neurohypophyseal hormones: opposite effects of vasopressin and oxytocin.

A classical task of experimental psychology, the retention of lists of words, was given twice to three groups of subjects treated with lysine vasopressin (LVP), oxytocin or saline. From a baseline session (no treatment) to a second session with treatment, the LVP and placebo groups showed an enhancement of the number of words remembered correctly, whereas the oxytocin group did not. Rather, oxytocin impaired memory performance. However, we cannot claim a memory enhancing effect of LVP, because placebo treatment enhanced memory performance to the same extent.

Adult↗

Dishabituating effects of an ACTH 4-9 analog in a vigilance task.

Ten male adults were tested in a vigilance task after oral administration of either 40 mg ACTH 4-9 analog, ORG 2766, or placebo in a single three hour session. EEG spectra, averaged auditory evoked responses, heart rate and blood pressure, and behavioral performance were measured during a vigilance task. ACTH 4-9 analog treatment led to a decreased inhibition of the central nervous system across the experiment: to less mean power density and faster center frequencies within the alpha band, and to less attenuated amplitudes of the components of the auditory vertex potential (P50, N100, P200). Treatment effects increased towards the end of the session and might indicate a dishabituating effect, probably due to suppression of inhibitory influences of limbic structures on mesencephalic reticular activity.

Adrenocorticotropic Hormone↗

Behavioral effects of vasopressin.

A single case study was executed to generate hypotheses concerning the role of vasopressin in human behavior. Classic tasks of experimental psychology, introspective and electrophysiological measures were applied in twelve sessions after randomized intake of vasopressin or a placebo. Results indicate that earlier stages of information processing in terms of attentional and arousal processes could be affected by the neuropeptide. Therefore the often claimed enhancement of memory processing seems to be an indirect effect of vasopressin.

Arousal↗

Evidence for extrapituitary mechanisms mediating the morning peak of plasma cortisol in man.

There is evidence for the existence of ACTH unrelated mechanisms in the regulation of cortisol secretion in man. This study was designed to elucidate the interrelationship between plasma ACTH and cortisol levels during the increase in cortisol levels, which occurs during morning hours. The results were compared with those of an artificial cortisol peak induced by administration of small amounts of ACTH, and with ACTH and cortisol values during insulin-induced hypoglycemia. In these control groups, the increase in cortisol levels was preceded by a large increase in ACTH levels; in the case of the physiological morning peak there was no adequate rise in mean ACTH levels. Thus, the spontaneously occurring increments in individual ACTH levels appear to be inappropriate for the increases in cortisol. This conclusion was corroborated by the finding that oscillations of plasma cortisol concentrations, comparable to the physiological morning peak, were demonstrable in ACTH-deficient patients when they were supplied with subthreshold amounts of exogenous ACTH. These findings argue against the classic concept that the adrenal cortex is invariably linked to immediately preceding episodes of pituitary ACTH secretion.

Adrenal Cortex↗

[Blood glucose, ACTH, cortisol, T4, T3 and rT3 after cholecystectomy. Comparative studies of continuous peridural anesthesia and neuroleptanalgesia].

15 patients (12 women and 3 men) undergoing cholecystectomy were randomized into two groups. 8 patients were operated on under continuous thoracic epidural anaesthesia in combination with light general anaesthesia. Postoperatively they were kept painfree by continuous infusion of an 0.125% solution of bupivacaine via epidural catheter at a rate of 0.25-0.3 ml/kg X h over a period of four days. The 7 patients in the control group were operated on under neuroleptanalgesia. Piritramide was given for postoperative analgesia. All patients received 40 ml/kg X day of electrolyte solution during the period of investigation. Blood was collected at 8 am, 12 am, 4 pm, 8 pm, and 12 pm on the day of operation and on the third postoperative day, at 8 am on the first and second postoperative day, and at 8 am, 12 am, and 4 pm on the fourth postoperative day. Plasma glucose, ACTH, cortisol, T4, T3, and reverse T3 were measured. During the operation and for 12 h thereafter a mild hyperglycaemia was observed in the neuroleptanalgesia group but not in the epidural group. The differences were significant. A rise in ACTH was seen in both groups during and shortly after operation. The increase in cortisol concentration following this ACTH release was significant only in the neuroleptanalgesia, but not in the epidural group. From the first to the fourth postoperative day ACTH levels were low and cortisol concentrations within the normal range. On the third day it appeared that a diurnal variation in cortisol levels was again present. Cortisol suppression following the administration of 2 mg dexamethasone on the fourth postoperative day was detectable in both groups. Of the thyroid hormones, T4 remained unchanged and at a normal level during the investigation. T3 decreased and reverse T3 increased significantly, the maximum rise being observed on the second day. There were no differences between the groups. These changes are defined as low T3 syndrome, following caloric deprivation, injury, and stress. The metabolic and hormonal alterations caused by cholecystectomy are marked only during operation and shortly thereafter and only in this period are they influenced by epidural analgesia. From the first postoperative day onwards they are almost negligible so that a mitigation by using continuous epidural analgesia is not to be expected.

Adrenocorticotropic Hormone↗

[Thoracic epidural anesthesia with 0.75% bupivacaine has no effect on ACTH-stimulated cortisol secretion].

The basis of this investigation was the question of whether low plasma cortisol concentrations during epidural anaesthesia are caused by sympathetic denervation of the adrenals. In 6 otherwise healthy patients undergoing upper abdominal operation 15-20 ml 0.75% bupivacaine was given via epidural catheter which had been inserted thoracically. Ringer's lactate solution 1,000 ml was infused during the time of onset of anaesthesia. When segmental epidural anaesthesia had spread from T2/3 to T12/L1/2 0.01 U/kg of ACTH were given intravenously. 5, 10, 20, and 30 minutes thereafter plasma ACTH and cortisol concentrations were measured. The same experimental procedure was carried out in a control group without epidural anaesthesia. The patients in both groups were unpremedicated and unanaesthetized. Plasma ACTH levels rose from 100 pg/ml (basic values) to 500-600 pg/ml immediately after ACTH injection in both groups and then decreased logarithmically. The increase of plasma cortisol concentrations was significant 15 minutes after the ACTH peak and rose from 0.28-0.3 mumol/l (10-11 micrograms/dl) up to 0.7 mumol/l (25 micrograms/dl) in both groups. We can, therefore, rule out that thoracic epidural anaesthesia with 0.75% bupivacaine impairs ACTH stimulated cortisol secretion.

Adrenocorticotropic Hormone↗

Influence of neuroactive drugs on corticosteroid feedback regulation of ACTH secretion in man.

Corticosteroid feedback effects on ACTH secretion in man can be manipulated by neuroactive drugs. In patients without endogenous corticosteroids (primary adrenocortical insufficiency) differential and integral feedback effects can be differentiated. When in these patients brain norepinephrine receptor activity was increased by desipramine, the normally negative differential feedback mechanism was converted into a positive one (paradoxical ACTH response). The pre-existing paradoxical ACTH response of patients with Cushing's disease after adrenalectomy was abolished after depletion of norepinephrine granules by means of reserpine.

Addison Disease↗

Distractability under the influence of an ACTH 4-9 derivative.

Event-related brain potentials, autonomic responses, and response latency under distraction conditions served to investigate the effects of an ACTH 4-9 derivative (ORG 2766) on attention. Male volunteers (45) received either 40 mg ORG 2766 or placebo in a double-blind setting. Two-stimulus trials with acoustic warning signal (S1) and acoustic S2 which had to be interrupted by immediate button press, preceded trials with distraction during the warning interval in 50% of the trials. A final period without distraction served to test for rebound effects. A reduction in early CNV was found in placebo subjects under distraction, while subjects under ORG 2766 showed no reduced early negativity, but increased late negativity under this condition. Peptide subjects differed from controls in evoked potential components, showing enhanced N1 and P3 amplitudes. Activity in the alpha band was elevated. Postexperimental systolic blood pressure was raised by 15 mm Hg under ORG 2766. Results are in agreement with previous findings and suggest ORG 2766 effects on distraction resistance and attention fixation.

Adrenocorticotropic Hormone↗

The meal-related peak in plasma cortisol is not mediated by radioimmunoassayable ACTH.

There is evidence for the existence of ACTH-unrelated mechanisms in the regulation of cortisol secretion in man. The present study was designed to elucidate the interrelations between plasma ACTH and cortisol levels during the 'midday surge' in cortisol concentrations. For comparison, a 'midday surge' was imitated by infusing small amounts of ACTH in dexamethasone-suppressed subjects. The meal-related cortisol bursts were not preceded by an adequate increase in ACTH levels. In contrast, markedly elevated ACTH levels were necessary to produce a comparable cortisol peak by administration of ACTH. Apparently, the meal-related bursts in cortisol levels were not mediated by radioimmunoassayable ACTH. These findings argue against the classic concept that the adrenal cortex is inseparably linked to immediately preceding hormonal events occurring in the hypothalamo-pituitary system.

Adrenocorticotropic Hormone↗