Biomedical subjects

H L Fehm

Publications and source records attributed to H L Fehm.

At least 91 records · Page 5Linked to original sources

PubMed1997

Regulation of human thought by neuropeptide ACTH 4-10: an analysis of the EEG's dimensional complexity.

The neuroactive 4-10 fragment of adrenocorticotropin (ACTH 4-10) has been found to impair electroencephalographic (EEG) signs of selective attention in previous studies. It was hypothesized that this effect reflects a more general influence of the peptide weakening the mutual inhibition among frontocortical neuronal networks. Therefore, ACTH 4-10 was expected to loosen attentional control not only over external input but also over internal thoughts. This study examined the effects of ACTH 4-10 on the dimensional complexity of the EEG recorded while subjects solved tasks of convergent analytical thinking and of divergent creative thinking and during mental relaxation. Subjects were tested 30 min after i.v. administration of placebo or ACTH 4-10 (2 mg). ACTH 4-10 enhanced dimensional complexity of the EEG. The effect primarily concerned frontocortical recordings during convergent thinking, which, following placebo, was associated with the lowest EEG dimension. ACTH 4-10 also impaired behavioral performance on tasks of convergent thought, when presented verbally. Results suggest that ACTH 4-10 counteracts the inhibitory control among cortical neuronal networks necessary for orderly analytical thinking.

Adrenocorticotropic Hormone↗

PubMed1997

[Quality in hospital treatment. How is it assured and who determines the guidelines?].

BACKGROUND: Internal quality control of medical performance in the interest of patient safety is not a new idea. In fact it has been implemented in varying degrees since the beginnings of medicine. ACTUAL SITUATION AND METHODS: Ever since hospitals are compelled by law to apply methods of quality assurance and external quality control, the question arises as to whether this law can achieve a concrete increase in quality of patient care or whether it rather serves to support economically motivated goals of health care policies, in the sense of an increase in efficiency of performance by physicians. Seen in the light of the overall situation of hospital care, the attempt to create mandatory quality standards is problematical. A reduction of hospital beds and a decrease in the average length of hospital stay contrasts the growing number of treated patients. This presents a problem which must be compensated for, despite cutbacks in budget and personnel. Methods of quality analysis are of the implicit as well as of the explicit type. Implicit methods are based on retrospective data analysis lacking previously set standards of comparison. These methods harbor the danger of viewer-dependent subjectivity (restricted reliability). Explicit methods are based upon comparison to previously defined standards. These methods are more objective, but often fail to give consideration to individual situations (restricted validity). The infrastructure necessary in order to sensibly apply quality control in the hospitals is not yet present in Germany. The software required in order to record and analyse data is still in a stage of development in many places. CONCLUSION: It is of importance not to leave external quality control to politicians and economists unfamiliar with the subject matter, but rather that quality control is implemented by experts in the medical field.

Economics, Hospital↗

PubMed1997

Effects of sleep and circadian rhythm on human circulating immune cells.

The role of nocturnal sleep for normal immune regulation and its relation to circadian rhythm was examined in 10 men participating in two 51-h sessions. One session included two regular wake-sleep cycles; the other included a night of sustained wakefulness followed by a night of recovery sleep. Blood was collected every 3 h to determine PBMC counts, including the enumeration of monocytes, NK cells, and lymphocyte subsets (CD19+, CD3+, CD4+, CD8+, HLA-DR+). Production of IL-1beta, TNF-alpha, IL-2, and IFN-gamma was determined after stimulation of whole blood samples with LPS and PHA, respectively. Concentrations of IL-6 and cortisol were assessed in plasma. Enumeration of cells indicated significant circadian rhythms for all PBMC subsets under conditions of sustained wakefulness. Compared with sustained wakefulness, nocturnal sleep acutely reduced the numbers of monocytes, NK cells, and counts of all lymphocyte subsets. However, in the afternoon and evening of the day following sleep, counts of NK cells and lymphocytes were significantly higher than after nocturnal wakefulness, indicating that effects of sleep interacted with those of the circadian pacemaker. Sleep markedly enhanced production of IL-2 by T cells (CD3+) but did not influence production of IL-1beta and TNF-alpha, or IL-6 concentrations. Effects of sleep were not mediated by changes in cortisol. The decrease in monocytes, NK cells, and lymphocytes, together with an increased production of IL-2 during sleep, may serve to support ongoing immune defense in extravascular lymphoid tissue during a time of diminished acute Ag challenge.

Adult↗

PubMed1997

Verbal memory after three months of intranasal vasopressin in healthy old humans.

In animals, evidence has been accumulated that vasopressin (VP) improves learning and memory. In humans, this effect was not consistently demonstrated, and attempts to restore age-related memory deficits by VP also remained inconsistent. Assuming that in old subjects a beneficial effect on memory occurs only after prolonged treatment with VP, we conducted a study in 26 healthy elderly persons receiving 40 IU of VP for three months through the intranasal route. The trial was randomized, placebo-controlled and held double-blind. Memory was assessed by the Auditory Verbal Learning Test (AVLT) requiring the subject to learn repeatedly presented lists of 15 words. Results demonstrated no general effect of long-term treatment with VP on memory in aged humans. However, recall of an interfering word list was improved, indicating a diminished proactive interference by the peptide. Additionally, VP influenced recall depending on the serial position of an item: it improved the primacy effect (i.e. recall of the first words of a list) and impaired the recency effect. This result may indicate an improved semantic encoding (i.e. a primary effect on processes of attention) after long-term administration of VP.

Administration, Intranasal↗

PubMed1997

Slow wave sleep drives inhibition of pituitary-adrenal secretion in humans.

During the first half of nocturnal sleep, the secretory response of the pituitary-adrenal axis to either CRH or vasopressin (VP) administration is reduced. Two experiments were performed aiming (i) to investigate the impact of sleep on the response to a combined CRH/VP administration and (ii) to specify the onset of sleep associated pituitary-adrenal suppression and its relation to specific sleep stages. In experiment I, we compared the effect of simultaneous administration of VP (0.5 IU i.v., within 6 min) and CRH (50 micrograms bolus i.v., in the third min of VP infusion) on the secretion of ACTH, cortisol and GH in healthy men during the first nocturnal epoch of slow wave sleep (SWS) and during nocturnal wakefulness. The increase of ACTH and cortisol concentrations after combined VP/CRH administration was distinctly higher during wakefulness than sleep (P < 0.01). In experiment II, CRH (30 micrograms/h, after an initial bolus of 30 micrograms) was continuously infused in 7 healthy men on 2 nights. On one of the nights, the men were allowed to sleep (between 23.00 h and 05.00 h) after a 3-h period of wakefulness, on the other night they stayed awake throughout the experiment. In both conditions, CRH enhanced ACTH/cortisol plasma levels. Compared with concentrations during continuous wakefulness, sleep and in particular SWS was associated with a suppression of ACTH/cortisol levels (P < 0.05). The findings further support an inhibitory influence of early nocturnal sleep on pituitary-adrenal activity. The effect appears to be strongest during SWS and is probably mediated via hypothalamic secretion of a release inhibiting factor of ACTH.

Adolescent↗

PubMed1997

Insulin stimulation of human adipocytes activates the kinase of only a fraction of the insulin receptors.

The degree of insulin receptor kinase activation by in situ stimulation was studied in isolated human adipocytes. Although maximal in situ stimulation increased the kinase activity approximately 10-fold, this activity could again be doubled by subsequent activation in a cell-free system. To investigate how in situ stimulation resulted in incomplete activation, receptors binding or not binding to anti-phosphotyrosine antibody (alpha-PY) were studied separately. Even after maximal insulin stimulation of the cells, approximately 50% of the receptors did not bind to alpha-PY and had low kinase activity. In the cell-free system, however, these receptors reached activity levels similar to the other receptors, suggesting that they were intact and that factors in their cellular environment had prevented their activation. The activity of the alpha-PY-binding receptors could only be slightly increased in the cell-free system, suggesting that almost complete activation had been attained in situ. In situ stimulation with increasing insulin concentrations increased the number of activated receptors rather than their individual activity. We conclude that factors in the in situ environment prevent insulin activation of approximately 50% of the insulin receptors in human adipocytes and might therefore be important regulators of insulin signaling.

Adipocytes↗

PubMed1997

Systemic immune changes following meal intake in humans.

Food intake represents a high intestinal antigen exposition requiring host defense. Besides local immune activation, this defense includes a coordinate systemic immune response, which may serve to support local immunity. This study examined influences of a standardized high-protein meal on peripheral blood mononuclear cell counts; on the in vitro mitogen-stimulated production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interferon-gamma; on the in vivo plasma levels of tumor necrosis factor-alpha and interleukin-6; and on plasma concentrations of cortisol and growth hormone. Ten healthy men (18-35 yr) participated in two experimental sessions in a balanced order. On one occasion, subjects fasted; on the other, they received a high-protein meal at 1230. Blood was sampled every 15 min. Whereas the numbers of neutrophils and platelets were increased for more than 2.5 h after meal intake (P < 0.01) lymphocyte counts decreased (P < 0.01). Meal intake also decreased the production of interferon-gamma but did not affect the production and plasma levels of the other cytokines. Changes in immune cell distribution and function were accompanied by a strong postprandial rise in plasma cortisol concentrations. Some of the systemic immune changes, like the emigration of lymphocytes, probably into extravascular abdominal tissues, may serve to support local immune defense.

Adult↗

PubMed1997

Cholecystokinin-induced effects on selective attention depend on level of activation.

Cholecystokinin (CCK)-like peptides, such as ceruletide, have been found to improve selective attention as indicated by the processing negativity (PN) of the event-related brain potential. The present study compared effects of ceruletide and placebo after intravenous administration of ceruletide on the PN in healthy subjects classified into two groups scoring high versus low on self-reported activation. Following placebo, PN (at Fz) was somewhat larger in subjects with low than high activation (p < 0.1). Administration of the CCK analog decreased PN in low-activation subjects but increased PN in the highly activated group (p < 0.01). Results suggest that the effects of CCK on selective attention depend on a modulation of central nervous mechanisms underlying activation.

Adult↗

PubMed1997

Evidence for central nervous effects of corticotropin-releasing hormone on gastric acid secretion in humans.

In animals, corticotropin-releasing hormone (CRH) has been shown to decrease gastric acid secretion after intracerebral administration. Evidence exists that in man peptides have a direct access to the brain upon intranasal administration. This study aimed at assessing brain-mediated effects of CRH on gastric pH after intranasal administration in humans. Eleven healthy men were tested on 2 occasions in a double-blind within-subject cross-over comparison during treatment with CRH (versus placebo) administered intranasally at a dose of 20 micrograms every 10 min. Gastric pH values were measured continuously by a gastral pH tube. After 2 h of intranasal treatment, 6 micrograms/kg pentagastrin was injected subcutaneously. The subject's mood was assessed by an adjective list (EWL-N) at the end of each experimental condition. Intranasal CRH increased pH baseline values from (mean +/- SE) 1.70 +/- 0.31 to 2.62 +/- 0.53 (corresponding to 54%), whereas during intranasal treatment with placebo pH values remained unchanged (p < 0.05). After injection of pentagastrin, pH values decreased to 0.73 +/- 0.04 during placebo and to 0.93 +/- 0.14 during CRH treatment (n.s.). During treatment with CRH, subjects felt less tired (p < 0.05) and deactivated (p < 0.05). Plasma cortisol and CRH levels were not affected by intranasal CRH, excluding mediation of the CRH effects via resorption into the bloodstream, and TSH levels were slightly decreased by the end of the treatment. Results confirm the notion of a pathway for CRH from the nose to the brain, initiating, via central nervous mechanisms, inhibition of gastric acid secretion and a change of mood in humans.

Adolescent↗

PubMed1997

Plasma epinephrine and norepinephrine concentrations of healthy humans associated with nighttime sleep and morning arousal.

We assessed the activity of the sympathetic nervous system during undisturbed nocturnal sleep and periods of wakefulness directly before and after sleep in healthy young men. Changes induced by periods of rapid eye movement and by morning awakening, both periods reported to demonstrate an enhanced risk for the onset of cardiovascular diseases, were of particular interest. In 13 healthy men (age, 18 to 35 years), blood for determination of epinephrine and norepinephrine was drawn every 7 minutes between 9:30 PM and 8:30 AM with the subjects resting in a strictly horizontal position. Lights were switched off at 11 PM until awakening at 7 AM. At 8:30 AM, subjects stood up and a final blood sample was drawn. Sleep was monitored somnopolygraphically, and heart rate and blood pressure were continuously measured. Average epinephrine but not norepinephrine concentrations were significantly lower during nocturnal sleep than during wakefulness before and after sleep. In parallel, heart rate and blood pressure declined significantly during sleep. During rapid eye movement sleep, both epinephrine and norepinephrine concentrations were significantly lower than during sleep stages 1 and 2 and slow-wave sleep. Whereas epinephrine concentrations gradually began to increase after morning awakening, norepinephrine levels were not significantly enhanced. However, standing up at the end of the experiment sharply increased norepinephrine concentrations by 180%, whereas epinephrine levels were less enhanced (46%) by the change of body position. This study suggests that the decrease in the activity of the sympathoadrenal branch of the sympathetic nervous system is probably due to an entrainment to the sleep-wake cycle, whereas the low activity of the noradrenergic branches depends mainly on horizontal body position during nocturnal sleep. The activities of the sympathoadrenal and noradrenergic branches of the sympathetic nervous system seem to be downregulated during rapid eye movement sleep. Awakening itself selectively enhances epinephrine levels. Subsequent orthostasis activates both the sympathoadrenal and, most prominently, the noradrenergic branches of the sympathetic nervous system.

Adolescent↗

PubMed1997

Blocking of central nervous mineralocorticoid receptors counteracts inhibition of pituitary-adrenal activity in human sleep.

Pituitary-adrenal activity has been found to be inhibited during early nocturnal sleep in humans. This inhibition was supposed to reflect a regulatory influence of hippocampal cells characterized by the expression of mineralocorticoid receptors (MR). Pituitary adrenal responsiveness to bolus injections of CRH (50 micrograms) was examined in each of nine healthy men on four occasions: CRH was injected either during early nocturnal sleep or at the same time of night while the subject was kept awake. Both of these conditions were run after pretreatment with the selective MR antagonist, canrenoate (2 x 200 mg, 0800 and 1700 h, preceding the experimental night) and after placebo administration. After placebo, sleep reduced ACTH and cortisol secretory responses to CRH to about 65% of the size observed during wakefulness (P < 0.05). After canrenoate, ACTH and cortisol secretory responses during sleep and wakefulness did not differ and were comparable with those obtained in placebo-treated subjects during wakefulness. Compared with placebo, canrenoate also distinctly reduced the time spent in slow-wave sleep (P < 0.005). The findings confirm an inhibition of pituitary-adrenal responsiveness during early sleep. The inhibition disappearance after blockage of MR suggests that sleep exerts this influence via central nervous MR-expressing cells. These cells seem to be simultaneously involved in the generation of slow-wave sleep.

Adrenocorticotropic Hormone↗

PubMed1996

Enhanced dynamic complexity in the human EEG during creative thinking.

This study shows that divergent thinking, considered the general process underlying creative production, can be distinguished from convergent, analytical thought based on the dimensional complexity of ongoing electroencephalographic (EEG) activity. EEG complexity over the central and posterior cortex was higher while subjects solved tasks of divergent than convergent thinking, and also higher than during mental relaxation. Over the frontal cortex, EEG complexity was comparable during divergent thinking and mental relaxation, but reduced during convergent thinking. Results indicate that the basic process underlying the generation of novel ideas expresses itself in a strong increase in the EEG's complexity, reflecting higher degrees of freedom in the competitive interactions among cortical neuron assemblies. Frontocortical EEG complexity being comparable with that during mental relaxation, speaks for a loosened attentional control during creative thinking.

Adult↗

PubMed1996

Brain potential changes after intranasal vs. intravenous administration of vasopressin: evidence for a direct nose-brain pathway for peptide effects in humans.

There is evidence that intranasal application of peptides is a way to circumvent the blood-brain barrier. This led us to compare the effects of arginine-vasopressin (AVP) on event-related potentials (ERPs) in healthy men (n = 15) after intranasal and after intravenous (i.v.) administration. In a double-blind, crossover study, subjects received on three different occasions 20 IU of AVP intranasally (IN), 1.5 IU of AVP i.v., and saline solution. ERPs were recorded during the subject's performance on a auditory attention task. Plasma concentrations of vasopressin during task performance were enhanced after AVP, with the increase after i.v. administration of AVP exceeding that after AVP (p < 0.05). Intranasal administration of AVP substantially increased the P3 component of the ERP (p < 0.05). Intranasal administration of AVP substantially increased the P3 component of the ERP (< 0.01). By contrast, i.v. administration of AVP had no consistent effects on the ERP responses. In supplementary experiments as well, i.v. administration of lower doses of AVP (0.1 and 0.025 IU) did not affect the ERP. Plasma vasopressin concentrations after the 0.025 IU dose in these experiments were comparable to those after intranasal administration of 20 IU AVP. The results provide functional evidence that in the human brain effects of peptides like AVP may be facilitated after IN as compared to i.v. administration.

Administration, Intranasal↗

PubMed1996

Event-related brain potentials during identification of tachistoscopically presented pictures.

In the present study in 20 healthy subjects, event-related potentials (ERPs) were used to investigate the identification of picture stimuli. Each of 36 landscape pictures and 36 scrambled pictures was presented by a tachistoscope repeatedly until the subject made an identification response. Presentation of one picture was finished after 12 exposures. On the average, landscapes were identified after 5.8 +/- 0.4 exposures; identification responses to scrambles were always wrong and occurred after 11.8 +/- 0.1 exposures. Latencies and amplitude measures were assessed for P2, P3, N400, and the slow wave (SW). Changes in P2 across stimulus presentations did not differ between landscapes and scrambles excluding this component from being indicative for the processing of stimulus meaning. Amplitude of P3 generally declined across presentations, but increased prior to identification for landscape pictures. N400 rapidly declined across presentations of landscapes, but less rapidly for scrambles. The SW increased across stimulus presentations. This increase was more pronounced for landscape than scrambled pictures. The pattern of ERP changes can be interpreted in a framework of a stepwise inhibition of spreading activation within semantic memory with progressing picture identification.

Adult↗

PubMed1996

Jealousy, general creativity, and coping with social frustration during the menstrual cycle.

Sensitivity to feelings of jealousy in women (n = 16) at three phases of their menstrual cycle differing in serum hormone concentrations (menses, preovulatory phase, midluteal phase) was investigated. Nonspecific electrodermal activity indicating sympathetic excitation was measured while subjects listened to stories and imagined situations inducing (i) nonsexual jealousy (the partner forms a deep emotional attachment to another woman), (ii) sexual jealousy (the partner has sexual intercourse with another woman), and (iii) no jealousy (social interaction lacking intense emotionality). Subjective ratings of the intensity of jealousy during both stories of jealousy were also assessed. In addition, changes in cognitive coping abilities, in general, and in the context of socially frustrating events, were assessed by tests of divergent thinking (creativity) and the Rosenzweig Picture Frustration Test. Frequency of nonspecific electrodermal reactions was generally enhanced during the preovulatory phase. This increase was particularly strong when the women listened to stories inducing nonsexual jealousy, i.e., a story characterized by cues of a complete loss of the partner's investment. Rated jealousy tended to be enhanced during the ovulatory phase, especially after the story of nonsexual jealousy. These changes in emotionality were paralleled by an improved divergent thinking performance and less aggressive coping with socially frustrating events around the time of ovulation.

Adaptation, Psychological↗

PubMed1996

Sensory processing during early and late nocturnal sleep.

The present experiments in 10 healthy men compared auditory evoked potentials (AEPs) and heart rate (HR) indicators of stimulus processing during early and late phases of nocturnal stage 2 sleep. Definition of early and late sleep relied on endocrine pituitary-adrenal secretory activity which is known to be inhibited during early nocturnal sleep but sharply increases during late sleep. AEPs and HR responses were recorded to trains of 10 tone pips (1000 Hz; interstimulus interval 15 s; intertrain interval > 3 min). On one night, tone pips were presented in the first part of sleep, on the other night tone presentation took place in the second part, with the order of conditions balanced across subjects. Amplitudes of N150 and N550 components of the AEP, and of acceleratory and deceleratory HR responses, were higher during the first than second part of nocturnal sleep (P < 0.05). Moreover, habituation of P240 and N550 amplitudes was slower during the first than second part of sleep (P < 0.05). In supplementary experiments, AEP and HR responses to the same stimuli did not differ between the first and second part of the night when subjects were waking during stimulation. Results indicate a reduced inhibitory control over cortical stimulus processing during early nocturnal sleep. This diminished inhibition of cortical processing together with other concomitant changes during early sleep (such as the enhanced inhibition of pituitary-adrenal secretion) may reflect a coordinated regulatory function of sleep possibly mediated by hippocampal mechanisms.

Acoustic Stimulation↗

PubMed1996

Sleep and signs of attention during 3 months of intranasal vasopressin: a pilot study in two elderly subjects.

Prominent features of aging include a decrease of attention abilities and loss of sleep. Although acute effects of vasopressin (VP) on these functions in the elderly remained inconsistent, beneficial effects of the peptide may develop only with subchronic treatment, which so far has not been tested. This pilot study examined the changes in: i) event-related brain potentials (ERPs) during an attention task, ii) mood, and iii) nocturnal sleep in two healthy elderly subjects during a 3-month period of VP treatment (40 IU/day). The period of VP treatment was preceded and followed by 4-week periods of placebo treatment. ERPs and mood were not consistently affected by VP. However, unexpectedly, VP improved sleep by markedly enhancing nocturnal slow-wave sleep (SWS, p < 0.05). These findings indicate that effects of subchronic treatment with VP involve mechanisms different from those mediating acute effects.

Administration, Intranasal↗

PubMed1996

Corticosteroid receptor mediated effects on mood in humans.

The present double-blind cross-over study aimed to discriminate effects of dexamethasone (DEX) and cortisol (CORT) on mood in ten healthy men. DEX is assumed to predominantly activate glucocorticoid receptors (GR) whereas CORT binds central nervous mineralocorticoid receptors (MR) as well as GR. Mood was assessed by an extensive adjective checklist (Eigenschaftswoerterliste) every morning during two 7-day experimental periods. During one of these periods, subjects were subchronically treated with placebo, during the other they received DEX (4 mg/day). On days 5 and 7 of these periods, (in a balanced manner) either placebo or CORT (10 mg/h) was infused during the night (9 h) before mood assessment. DEX, acutely, enhanced activation, concentration, and arousal (p < .05). During prolonged DEX administration, the energizing effect of the glucocorticoid decreased, but emotional arousability and negative feelings (anger, sadness) were significantly enhanced. CORT administered during prolonged DEX treatment, counteracted these negative feelings, and enhanced scores on a dimension of "high spirits". Sole administration of CORT also enhanced "high spirits" (p < .05) and, like DEX, activation and concentration (p < .05). Results suggest GR to mediate an energizing effect and, with prolonged activation, a dysphoric influence on mood. Predominant activation of MR appears to mediate changes towards euphoric mood.

Administration, Oral↗