Timing the end of nocturnal sleep.
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Adrenocorticotropic Hormone↗
Biomedical subjects
M Mölle
Publications and source records attributed to M Mölle.
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↗
Brain potentials and attention after acute and subchronic intranasal administration ofACTH 4-10 and desacetyl-alpha-MSH in humans.
Neuropeptides related to adrenocorticotropin (ACTH) are potent regulators of neurobehavioral functions. In humans, ACTH and its behaviorally active fragment ACTH 4-10 have been consistently found to diminish event-related brain potential (ERP) signs of focussing attention. This study aimed at (1) evaluating effects of ACTH 4-10 on ERP indicators of attention in healthy controls after intranasal administration of the peptide. This route of administration has been proposed to provide a more direct access to the brain than the intravenous administration of the peptide, (2) comparing acute effects and effects of a subchronic treatment with ACTH 4-10, and (3) comparing effects of ACTH 4-10 with those of desacetyl-alpha-MSH (corresponding to ACTH 1-13 amide) which like ACTH 4-10 binds to subgroups of the melanocortin receptor family. Double-blind placebo-controlled experiments were completed in 54 healthy young subjects. ERPs were recorded while the subject performed an auditory selective attention task. Moreover, a modified Stroop interference test including motivational (food, sex) and nonmotivational words was performed. Acute intranasal administration of ACTH 4-10 (1 mg) reduced the processing negativity (PN) of the ERP over frontal and central cortical areas (p < 0.05) indicating diminished focussing of attention. Moreover, on this condition subjects were more prone to interference on the Stroop task especially with motivational words (p < 0.05). Subchronic administration of ACTH 4-10 (1 mg/day over 6 weeks) did not affect PN and Stroop performance. Acute intranasal administration of desacetyl-alpha-MSH at equimolar doses (1.68 mg) also remained ineffective. However, some measures of Stroop performance appeared to improve after subchronic desacetyl-alpha-MSH treatment. Results confirm an acute decrease in focussing of attention after ACTH 4-10. These effects of intranasal administration are likely to reflect a direct action of the peptide on respective brain functions. Moreover, they were specific to ACTH 4-10 and were not obtained after equimolar doses of desacetyl-alpha-MSH, thus excluding a mediation via the known melanocortin receptors.
Administration, Intranasal↗
Scalp recorded direct current brain potentials during human sleep.
The direct current (DC) potential recorded from the scalp of awake humans has been considered a reflection of general changes in cortical excitability. This study examined DC potential shifts in humans during a night of continuous sleep. Standard polysomnographic recordings and skin temperature were measured simultaneously. Contrary to expectations, average DC potential level indicated higher negativity during nonrapid eye movement (NREM) sleep than REM sleep and wakefulness. Moreover, a dynamic regulation of the DC potential level was revealed in association with the NREM-REM sleep cycle comprising four successive phases: (i) a steep 'NREM-transition-negative shift' during the initial 10-15 min of the NREM sleep period; (ii) a more subtle 'NREM-positive slope' during the subsequent NREM sleep period; (iii) a steep 'REM-transition-positive shift' starting shortly prior to the REM sleep period, and (iv) a 'REM-negative slope', characterizing the remaining greater part of the REM sleep period. DC potential changes were only weakly related to changes in slow-wave activity (r2 < 0.18). The NREM-negative slope and REM-positive slope could reflect, respectively, gradually increasing and decreasing cortical excitability resulting from widespread changes in the depolarization of apical dendrites. In contrast, the NREM-transition-negative shift and the REM-transition-positive shift may reflect the progression and retrogression, respectively, of a long-lasting hyperpolarization in deeply lying neurons.
Adult↗
The incidence of DNA aneuploidy in multiple myeloma does not correlate with stage of disease.
The bone marrow of 47 patients with multiple myeloma (MM), 2 patients with plasma cell leukemia, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS) was analyzed by flow cytometry for the detection of DNA aneuploidy. The question to be addressed was whether a correlation exists between the incidence of DNA aneuploidy and the stage of disease. With one-parameter analysis of DNA staining, a DNA aneuploidy was detectable in 17 of 60 patients. The detection rate for DNA aneuploidies could be increased to 37 of 60 patients with the second method, the simultaneous measurement of DNA content in additional immunophenotyped cells (CD38 or B-B4). In MGUS and the early stages of MM, the discrepancy between both methods was higher than in stage III MM. There were no statistical differences in the incidence of DNA aneuploidy between MGUS or the early stages of MM and stage III MM (21/32 patients vs 16/26 patients). The CD56 expression in plasma cells was significantly higher in cases of DNA aneuploidy (mean +/- SD, 64.7% +/- 33.65% vs 39.3% +/- 36.69%; P = .028). Comparing the ratio of diploid to DNA aneuploid with that of CD56+ to CD56- plasma cells, a correlation was found in MGUS (r = 0.7320) in the early stages of MM, I and II (r = 0.8023), but not in stage III MM. Based on these data, the dual-staining method for DNA content in immunophenotyped cells is preferred for the detection of DNA aneuploidy, especially in the early stages of MM and in MGUS. The clinical importance of a classification of DNA aneuploidy and CD56 antigen expression together is proposed for testing.
ADP-ribosyl Cyclase↗
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↗
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↗
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↗
Event-related gamma band activity during passive and active oddball tasks.
The EEG was recorded during passive listening and active attending to tone pips of an oddball stimulus sequence, and the time course of event-related gamma band activity (30-60 Hz) was compared with event-related potential (ERP) components. In the conventional frequency range (0.1-4.3 Hz) mismatch negativity (MMN) was produced in the passive listening condition. Concurrent with MMN, the power of event-related gamma activity to the deviant stimulus was higher than gamma activity elicited by the preceding standard stimulus. The transition from the N2b to the P3 wave, produced during active attention, was associated with a decrease in gamma band power upon the deviant tone. The results show the differential generation of gamma band power depending on preattentive and attentive stimulus processing.
Acoustic Stimulation↗
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↗
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↗
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↗
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↗
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↗
The angiotensin converting enzyme inhibitors fosinopril and enalapril differ in their central nervous effects in humans.
BACKGROUND: Although the antihypertensive actions of different angiotensin converting enzyme (ACE) inhibitors are comparable, they may affect central nervous activity, mood and well-being differently. Thus, central nervous actions of ACE inhibitors may represent an essential factor determining compliance with antihypertensive therapy. OBJECTIVE: To compare central nervous effects of the biochemically different ACE inhibitors fosinopril and enalapril in healthy men. METHODS: In a double-blind cross-over study, auditory event-related brain potentials and heart rate variability were assessed 6 h after oral intake of placebo, enalapril (10 mg) and fosinopril (20 mg) with the doses being equipotent with regard to systemic ACE inhibition. Plasma concentrations of noradrenaline, adrenaline, vasopressin and cortisol were determined 3 and 6 h after drug intake. Central nervous effects mediated via direct systemic hypotensive actions were avoided (although not completely ruled out) by including only subjects (n = 14) who displayed no substantial drop in blood pressure following intake of the ACE inhibitors. RESULTS: Enalapril, but not fosinopril, enhanced the N1 component and the N1-P2 amplitude of the event-related brain potential (P < 0.05). In addition, enalapril enhanced plasma noradrenaline concentrations (P < 0.05). A similar effect of fosinopril failed to reach significance. There was no clear-cut effect of ACE inhibition on heart rate variability, and also plasma concentrations of adrenaline, vasopressin and cortisol remained unaffected. CONCLUSION: The results suggest an enhancing effect of enalapril on mechanisms regulating stimulus-induced cortical arousal and central nervous sympathetic outflow. The effects diverging between enalapril and fosinopril indicate that access to human brain functions differs among the various types of ACE inhibitors.
Adult↗
[Disseminated aspergillosis and mucormycosis. A case report].
This paper reports a simultaneous pulmonary infection due to Aspergillus fumigatus and Rhizomucor pusillus which evolved to disseminated aspergillosis and mucormycosis in a leukaemic and neutropenic 40-year-old woman. Both fungi were cultured ante mortem from bronchial secretion. Although high doses of intravenous amphotericin B were administered, the course of the infection was fatal. At autopsy, aspergilli were demonstrated by histology in lungs and brain, and zygomycetes were found to have invaded liver and kidneys.
Adult↗
Greater efficacy of episodic than continuous growth hormone-releasing hormone (GHRH) administration in promoting slow-wave sleep (SWS).
It has been suggested that growth hormone (GH)-releasing hormone (GHRH) stimulates the surge in GH and enhances slow-wave sleep (SWS), two phenomena that characterize the beginning of nocturnal sleep. However, in human studies the effects of systemic GHRH administration on sleep were not consistent. This may reflect the differential influence of administration procedures being episodic in one of the above studies, but either a continuous infusion or a single bolus in the others. The present study in healthy volunteers compared changes in nocturnal sleep following 200 micrograms GHRH administered iv either episodically (4 boluses of 50 micrograms each at 2200, 2300, 2400, and 0100 h) or as a continuous infusion (57 micrograms/h between 2130 and 0100 h). Time spent in stage 4 of SWS on nights of episodic GHRH administration significantly exceeded that on nights of continuous GHRH administration (P < 0.01). Compared with a placebo condition, episodic administration of GHRH enhanced SWS (P < 0.01) and rapid eye movement (REM) sleep (P < 0.05) and diminished time spent in wakefulness and sleep stage 1 (P < 0.05). Effects of continuous GHRH infusion on sleep generally remained insignificant compared with placebo. Plasma GH concentrations were enhanced during both conditions of GHRH administration (P < 0.01), with the increase following episodic administration slightly exceeding that during continuous infusion (P < 0.05). The results support a greater physiological efficacy of episodic GHRH stimulation in promoting sleep.
Adult↗
[Prophylaxis and therapy of fungal infections in oncology].
The observation of a considerable incidence of fungal infections in oncology patients has promoted a large number of studies both on prophylaxis and treatment in this patient group. Trials using triazoles, especially fluconazole, have shown effect in preventing fungal infections. In neutropenic patients, their role in therapy still remains less clear. Amphotericin B is the drug of choice for most life-threatening infections. With this drug, efforts concentrate upon the amelioration of side effects by sodium loading, administration in lipid emulsions or liposomes. The use of AMB as low-dose systemic prophylaxis or by inhalation needs further study.
Amphotericin B↗