Manolo Ernesto Beelke

2017; 8(3): 555614. DOI: 10.19080/JPCR.2017.03.555614

Medical affairs and marketing worked hand in hand but at the
same time this relationship was sometimes also conflictual. It was
common for the marketing department to see medical affairs as
the “sales prevention department”. In this article, Manolo Beelke,
Senior Medical Director, Medical & Scientific Affairs at Worldwide
Clinical Trials, defines how this vision is changing now towards a
solutions-focused partnership with marketing. These changes offer
the opportunity for a… Mehr anzeigen

Medical affairs and marketing worked hand in hand but at the
same time this relationship was sometimes also conflictual. It was
common for the marketing department to see medical affairs as
the “sales prevention department”. In this article, Manolo Beelke,
Senior Medical Director, Medical & Scientific Affairs at Worldwide
Clinical Trials, defines how this vision is changing now towards a
solutions-focused partnership with marketing. These changes offer
the opportunity for a new type of partnership between medical
affairs and commercial activities. This collaboration can create
scientifically-minded and medically-driven marketing. Weniger anzeigen

Patent foramen ovale (PFO) is an independent risk factor for ischemic stroke by means of paradoxical embolization, due to right-to-left shunt (RLSh). The higher prevalence of PFO found in OSAS respect to the general population could be due to the chronic effect of the intrathoracic pressure changes during periods of obstructive sleep apnea. This study aimed to re-evaluate the magnitude of RLSh in subjects with obstructive sleep apnea syndrome (OSAS) and diagnosed PFO after a long period of CPAP… Mehr anzeigen

Patent foramen ovale (PFO) is an independent risk factor for ischemic stroke by means of paradoxical embolization, due to right-to-left shunt (RLSh). The higher prevalence of PFO found in OSAS respect to the general population could be due to the chronic effect of the intrathoracic pressure changes during periods of obstructive sleep apnea. This study aimed to re-evaluate the magnitude of RLSh in subjects with obstructive sleep apnea syndrome (OSAS) and diagnosed PFO after a long period of CPAP treatment.
Assessment of PFO and concomitant OSAS. Application of CPAP treatment with control of compliance. Re-evaluation of RLSh through the assessed PFO at follow-up (after 41  6 months) by means of Transcranial Doppler with contrast medium injected in antecubital vein. Participants: Eighteen OSAS subjects affected by PFO (mean age 56 ± 11 years). Interventions: They underwent Transcranial Doppler, with injection of agitated saline solution mixed with air during normal breathing and Valsalva maneuver. CPAP treatment has chronically applied by 15 of 18 subjects (83%). RLSh magnitude did not change in the 3 subjects, who had not applied the CPAP treatment. In 4 of the 15 subjects, who used the CPAP treatment, no RLSh could be recorded (PFO closure). The difference between CPAP-user and CPAP–non-users was significant (p<0.01). In the other 11 of this subgroup RLSh magnitude was reduced respect to baseline recording. Multiple regression analysis modelling, magnitude of RLSh correlated mainly to the weekly CPAP use (days/week) negatively and the condition of atrial fibrillation positively.

Conclusions: In the nocturnal sleep period RLSh can occur during single obstructive apneas in subjects with OSAS and concomitant presence of PFO. This can be a risk factor for cerebrovascular diseases. This risk could probably increase proportionally to the respiratory disturbance index of these subjects. Compliance to CPAP treatment is able to reduce the magnitude of RLSh. Weniger anzeigen

The increasing amount of highly effective treatment options in relapsing forms of multiple sclerosis (MS) requires
innovative clinical trial design strategies. These strategies may encompass the application of adaptive designs as
well as the adoption of innovative primary outcome measurements. The offered advantages would include, among
others, shorter study follow-up periods and reduction in the number of patients either on placebo or on non-suitable
dosages of the small molecules… Mehr anzeigen

The increasing amount of highly effective treatment options in relapsing forms of multiple sclerosis (MS) requires
innovative clinical trial design strategies. These strategies may encompass the application of adaptive designs as
well as the adoption of innovative primary outcome measurements. The offered advantages would include, among
others, shorter study follow-up periods and reduction in the number of patients either on placebo or on non-suitable
dosages of the small molecules or biological products under examination. Changing the primary endpoint during the
study conduct additionally represents an option, when the primary endpoint originally is either a composite endpoint
of Magnetic Resonance Imaging (MRI) and clinical variables or a unitary endpoint of clinical variables. The new
outcome measurement of no-evidence-of-disease activity (NEDA) – the former disease activity free (DAF) status,
might represent an attractive approach and NEDA may become a new standard for clinical trials in relapsing MS
(RMS), particularly for pivotal Phase III trials, though also earlier phase trials and exploratory clinical research might
benefit from this endpoint. Future studies in RMS could incorporate NEDA as a primary endpoint and utilize the
adaptive design methodology in order to reduce the sample size and the duration of new therapeutic agents’
clinical development.
Keywords: Relapsing multiple sclerosis, No evidence of disease activity (NEDA), Disease activity free (DAF),
Adaptive design, Primary endpoint Weniger anzeigen

BACKGROUND:

Interferon beta (IFNb) reduces relapse frequency and disability progression in patients with multiple sclerosis (MS).
OBJECTIVES:

Early identification of prognostic biomarkers of IFNb-treated patients will allow more effective management of MS.
METHODS:

The IMPROVE study evaluated subcutaneous IFNb versus placebo in 180 patients with relapsing-remitting MS. Magnetic resonance imaging scans, clinical assessments, and blood samples were obtained at baseline… Mehr anzeigen

BACKGROUND:

Interferon beta (IFNb) reduces relapse frequency and disability progression in patients with multiple sclerosis (MS).
OBJECTIVES:

Early identification of prognostic biomarkers of IFNb-treated patients will allow more effective management of MS.
METHODS:

The IMPROVE study evaluated subcutaneous IFNb versus placebo in 180 patients with relapsing-remitting MS. Magnetic resonance imaging scans, clinical assessments, and blood samples were obtained at baseline and every 4 weeks from every participant. Thirty-nine biomarkers (32 transcripts; seven proteins) were studied in 155 patients from IMPROVE. Therapeutic response was defined by absence of new combined unique lesions, relapses, and sustained increase in Expanded Disability Status Scale over 1 year. A machine learning approach was used to examine the association between biomarker expression and treatment response.
RESULTS:

While baseline levels of individual genes were relatively poor predictors, combinations of three genes were able to identify subjects with sub-optimal therapeutic responses. The triplet CASP2/IRF4/IRF6, previously identified in an independent dataset, was tested among other combinations. This triplet showed acceptable predictive accuracy (0.68) and specificity (0.88), but had relatively low sensitivity (0.22) resulting in an area under the curve (AUC) of 0.63. Other combinations of biomarkers resulted in AUC of up to 0.80 (e.g. CASP2/IL10/IL12Rb1).
CONCLUSIONS:

Baseline expression, or induction ratios, of specific gene combinations correlate with future therapeutic response to IFNb, and have the potential to be prognostically useful. Weniger anzeigen

Comment on
A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. [Neurology. 2011]

Study design of the SOLAR study

Recent studies have demonstrated the immunomodulatory properties of vitamin D, and vitamin D deficiency may be a risk factor for the development of MS. The risk of developing MS has, in fact, been associated with rising latitudes, past exposure to sun and serum vitamin D status. Serum 25-hydroxyvitamin D [25(OH)D] levels have also been associated with relapses and disability progression. The identification of risk factors, such as vitamin D deficiency, in… Mehr anzeigen

Study design of the SOLAR study

Recent studies have demonstrated the immunomodulatory properties of vitamin D, and vitamin D deficiency may be a risk factor for the development of MS. The risk of developing MS has, in fact, been associated with rising latitudes, past exposure to sun and serum vitamin D status. Serum 25-hydroxyvitamin D [25(OH)D] levels have also been associated with relapses and disability progression. The identification of risk factors, such as vitamin D deficiency, in MS may provide an opportunity to improve current treatment strategies, through combination therapy with established MS treatments. Accordingly, vitamin D may play a role in MS therapy. Small clinical studies of vitamin D supplementation in patients with MS have reported positive immunomodulatory effects, reduced relapse rates and a reduction in the number of gadolinium-enhancing lesions. However, large randomized clinical trials of vitamin D supplementation in patients with MS are lacking. SOLAR (Supplementation of VigantOL(®) oil versus placebo as Add-on in patients with relapsing-remitting multiple sclerosis receiving Rebif(®) treatment) is a 96-week, three-arm, multicenter, double-blind, randomized, placebo-controlled, Phase II trial (NCT01285401). SOLAR will evaluate the efficacy of vitamin D(3) as add-on therapy to subcutaneous interferon beta-1a in patients with RRMS. Recruitment began in February 2011 and is aimed to take place over 1 calendar year due to the potential influence of seasonal differences in 25(OH)D levels. Weniger anzeigen

Case report

The effect of the neuroactive steroids progesterone, dihydroprogesterone and tetrahydroprogesterone on myelin abnormalities induced by diabetes was studied in the sciatic nerve of adult male rats treated with streptozotocin. Streptozotocin increased blood glucose levels and decreased body weight gain, parameters not affected by steroids. Streptozotocin increased the number of fibers with myelin infoldings in the axoplasm, 8 months after the treatment. Chronic treatment for 1 month with… Mehr anzeigen

The effect of the neuroactive steroids progesterone, dihydroprogesterone and tetrahydroprogesterone on myelin abnormalities induced by diabetes was studied in the sciatic nerve of adult male rats treated with streptozotocin. Streptozotocin increased blood glucose levels and decreased body weight gain, parameters not affected by steroids. Streptozotocin increased the number of fibers with myelin infoldings in the axoplasm, 8 months after the treatment. Chronic treatment for 1 month with progesterone and dihydroprogesterone resulted in a significant reduction in the number of fibers with myelin infoldings to control levels. Treatment with tetrahydroprogesterone did not significantly affect this myelin alteration. These results suggest that neuroactive steroids such as progesterone and dihydroprogesterone may represent therapeutic alternatives to counteract peripheral myelin alterations induced by diabetes. Weniger anzeigen

OBJECTIVE:
Total sleep time and slow-wave sleep (SWS) are frequently reported to be reduced in anorectics. A preliminary study showed that slow-wave activity (SWA, 0.5-4.5 Hz) is decreased in anorectic adolescents. The present study investigates whether this reduction is the result of the increased sleep fragmentation or is dependent on an intrinsic weakness of SWA-producing mechanisms.
DESIGN:

Statistical analysis of spectral electroencephalogram data recorded during sleep from a… Mehr anzeigen

OBJECTIVE:
Total sleep time and slow-wave sleep (SWS) are frequently reported to be reduced in anorectics. A preliminary study showed that slow-wave activity (SWA, 0.5-4.5 Hz) is decreased in anorectic adolescents. The present study investigates whether this reduction is the result of the increased sleep fragmentation or is dependent on an intrinsic weakness of SWA-producing mechanisms.
DESIGN:

Statistical analysis of spectral electroencephalogram data recorded during sleep from a group of anorectics and a control group.
SETTING:

Polysomnographic data were recorded in single rooms in the hospital for 1 night following an adaptation night.
PARTICIPANTS:

20 adolescent anorectic girls (13.9 +/- 2.0 years) and 12 age-matched control subjects.
INTERVENTIONS:

Refeeding and psychotherapy.
MEASUREMENTS AND RESULTS:

Anorectics had an increase of wakefulness after sleep onset, a higher number of arousals, and a reduction of SWS and SWA during total sleep time. No relationship between the reduction of SWA and duration of illness was found, while a relationship between SWA decrease and the level of emaciation (body mass index) was present. The analysis limited to the first non-rapid eye movement sleep cycle did not show any difference between the 2 groups in the number of awakenings and arousals. Nevertheless, anorectics showed a reduction of SWS and SWA.
CONCLUSIONS:
Sleep of anorectic patients seems to be characterized by an impairment of SWA-producing mechanisms independent of the increased sleep fragmentation. This is probably related to the primary pathophysiologic characteristics of the illness but could also reflect secondary functional and anatomic alterations of the brain. Weniger anzeigen

STUDY OBJECTIVES:
Night work can be dangerous because both circadian sleep propensity (process C) and sleep pressure due to the prolonged wakefulness (process S) contribute to the reduction of vigilance levels. As naps are a countermeasure to sleepiness, this study evaluates the role they play in preventing sleep-related accidents in Italian shift-working police drivers.
DESIGN/SETTING/PARTICIPANTS:

The study concerns highway car accidents that occurred to Italian shift-working… Mehr anzeigen

STUDY OBJECTIVES:
Night work can be dangerous because both circadian sleep propensity (process C) and sleep pressure due to the prolonged wakefulness (process S) contribute to the reduction of vigilance levels. As naps are a countermeasure to sleepiness, this study evaluates the role they play in preventing sleep-related accidents in Italian shift-working police drivers.
DESIGN/SETTING/PARTICIPANTS:

The study concerns highway car accidents that occurred to Italian shift-working police drivers; it was performed in 2 steps: a retrospective analysis of the overall number of accidents that occurred during the years 1993--1997 (n, 1195), followed by a validation analysis of a smaller cohort of accidents prospectively collected during 2003 (n, 84).
INTERVENTIONS:N/A.
MEASUREMENTS AND RESULTS:
RETROSPECTIVE ANALYSIS: The influence of process S, process C, driver characteristics, and context conditions on accident risk, estimated by means of Cox hazard regression, revealed that nighttime accident risk was mainly influenced by process S levels. Consequently, an experimental mathematical model linking the hourly observed number of accidents to process S levels was designed. Its generalization to the theoretical case of drivers omitting naps showed an increase of about 38% of accidents. PROSPECTIVE ANALYSIS: In order to validate our results, we compared retrospective and prospective sleep patterns: no statistical difference was found. Again, the hourly number of accidents increased with homeostatic sleep pressure; the theoretical efficacy of napping was quantified in 48% accidents decrease.
CONCLUSIONS:
Our data seem to confirm that napping before working a night shift is an effective countermeasure to alertness and performance deterioration associated with night work. Moreover, this self-initiated behavior could have a prophylactic efficacy in reducing the number of car accidents. Weniger anzeigen

BACKGROUND AND PURPOSE:

Periodic limb movement disorder (PLMD) is frequently accompanied by awakenings or signs of EEG arousal. However, it is matter of debate whether EEG arousals trigger leg movements or both EEG arousal and leg movements are separate expressions of a common pathophysiological mechanism. Previous studies showed that cardiac and cerebral changes occur in association with periodic limb movements (PLMs), and that a combining increase in delta activity and in heart rate… Mehr anzeigen

BACKGROUND AND PURPOSE:

Periodic limb movement disorder (PLMD) is frequently accompanied by awakenings or signs of EEG arousal. However, it is matter of debate whether EEG arousals trigger leg movements or both EEG arousal and leg movements are separate expressions of a common pathophysiological mechanism. Previous studies showed that cardiac and cerebral changes occur in association with periodic limb movements (PLMs), and that a combining increase in delta activity and in heart rate (HR) occurs before the onset of PLMs.
PATIENTS AND METHODS:

This paper presents some preliminary data, obtained from a sample of 5 subjects with PLMD not associated to restless legs syndrome. To describe the temporal pattern of cardiac and EEG activities changes concomitant with PLMs in NREM sleep we used time frequency analysis technique.
RESULTS:

PLM onset is heralded by a significant activation of HR and delta activity power, beginning 4.25 and 3 s respectively before PLMs onset, with PLMs onset and arousal onset falling together.
DISCUSSION:

Delta and HR variations herald PLMs and activation of fast EEG frequencies. Such a stereotyped pattern is common in PLMs and in spontaneous or stimuli-induced arousals. Moreover a similar pattern seems to encompass the CAP phenomenon. The whole of these phenomena can be linked to the activity of a common brainstem system, which receives peripheral inputs, regulating the vascular, cardiac and respiratory activities and synchronizing them to cortical oscillations of EEG. Weniger anzeigen

Visual contrast stimulation evokes in man an oscillatory mass response at approximately 20.0-35.0 Hz, consistent with stimulus-dependent synchronous oscillations in multiunit animal recordings from visual cortex, but shorter in duration and phase-locked to stimulus. A factor analysis was applied to characterize the signal structure under stimulus conditions inducing an oscillatory response and to identify possible subcomponents in normal volunteers.
METHODS:

Contrast stimuli were… Mehr anzeigen

Visual contrast stimulation evokes in man an oscillatory mass response at approximately 20.0-35.0 Hz, consistent with stimulus-dependent synchronous oscillations in multiunit animal recordings from visual cortex, but shorter in duration and phase-locked to stimulus. A factor analysis was applied to characterize the signal structure under stimulus conditions inducing an oscillatory response and to identify possible subcomponents in normal volunteers.
METHODS:

Contrast stimuli were gratings with a sinusoidal luminance profile (9.0 degrees; 5.0 cycle/degree; 80% contrast; reversal 1.06 Hz). The amplitude spectrum of the signal was computed by Discrete Fourier Transform (DFT) and the oscillatory response was separated from the corresponding visually evoked potential (VEP) by DFT high-pass filter at 19.0 Hz. Nine consecutive waves were identified in all subjects (60 volunteers), with amplitudes/latencies consistent with normative studies. A factor analysis was computed 1- in the frequency domain, on the amplitude values of the signal components (2 Hz resolution), and 2- in the time domain, on the latencies/amplitudes of the averaged VEP and oscillatory responses.
RESULTS:

(1) Two non-overlapping factors accounted for the approximately 2-20.0 and approximately 20.0-40.0 Hz signal components, with separation of the approximately 20.0-35.0 Hz oscillatory response from low frequency VEPs. (2) Two factors on latencies and one factor on amplitudes (independent of each other and from those of VEPs) accounted for the average approximately 20.0-35.0 Hz oscillatory response.
CONCLUSIONS:

The factor structure further indicates an oscillatory structure and some independence from conventional VEPs of the human oscillatory response to contrast, with a separation between the oscillatory response early and late waves possibly reflecting functional differences. Weniger anzeigen

A number of phasic events influence sleep quality and sleep macrostructure. The detection of arousals and the analysis of cyclic alternating patterns (CAP) support the evaluation of sleep fragmentation and instability. Sixteen polygraphic overnight recordings were visually inspected for conventional Rechtscaffen and Kales scoring, while arousals were detected following the criteria of the American Sleep Disorders Association (ASDA). Three electroencephalograph (EEG) segments were associated to… Mehr anzeigen

A number of phasic events influence sleep quality and sleep macrostructure. The detection of arousals and the analysis of cyclic alternating patterns (CAP) support the evaluation of sleep fragmentation and instability. Sixteen polygraphic overnight recordings were visually inspected for conventional Rechtscaffen and Kales scoring, while arousals were detected following the criteria of the American Sleep Disorders Association (ASDA). Three electroencephalograph (EEG) segments were associated to each event, corresponding to background activity, pre-arousal period and arousal. The study was supplemented by the analysis of time-frequency distribution of EEG within each subtype of phase A in the CAP. The arousals were characterized by the increase of alpha and beta power with regard to background. Within NREM sleep most of the arousals were preceded by a transient increase of delta power. The time-frequency evolution of the phase A of the CAP sequence showed a strong prevalence of delta activity during the whole A1, but high amplitude delta waves were found also in the first 2/3 s of A2 and A3, followed by desynchronization. Our results underline the strict relationship between the ASDA arousals, and the subtype A2 and A3 within the CAP: in both the association between a short sequence of transient slow waves and the successive increase of frequency and decrease of amplitude characterizes the arousal response. Weniger anzeigen

OBJECTIVE:

The aim of this study was to evaluate the impact of chronic vagus nerve stimulation (VNS) on sleep/wake background EEG and interictal epileptiform activity (IEA) of patients with medically refractory epilepsy.
METHODS:

From a broader sample of 10 patients subjected to baseline and treatment polysomnographies, spectral analysis and IEA count have been performed on 6 subjects' recordings, comparing the results by means of statistical analysis.
RESULTS:

An… Mehr anzeigen

OBJECTIVE:

The aim of this study was to evaluate the impact of chronic vagus nerve stimulation (VNS) on sleep/wake background EEG and interictal epileptiform activity (IEA) of patients with medically refractory epilepsy.
METHODS:

From a broader sample of 10 patients subjected to baseline and treatment polysomnographies, spectral analysis and IEA count have been performed on 6 subjects' recordings, comparing the results by means of statistical analysis.
RESULTS:

An overall increase in EEG total power after VNS has been observed, more marked in NREM sleep; collapsing EEG power spectra into 5 frequency bands, we have found a statistically significant increase in delta and theta in NREM sleep, and of alpha in wakefulness and REM sleep. The incidence of IEA is diminished, although not significantly; only the duration of discharges is significantly diminished.
CONCLUSIONS AND SIGNIFICANCE:

Long-term VNS produces an enhancement in sleep EEG power of medically refractory epileptic patients. These results may be related to a better structured composition of EEG, and it is possible that chronic VNS may have a major role in enhancing the brain's ability to generate an electrical activity. Weniger anzeigen

Our study aimed to evaluate the existence and entity of changes in sleep structure following vagus nerve stimulation in patients with refractory epilepsy.
METHOD:

A polysomnographic study was performed on the nocturnal sleep of 10 subjects with refractory epilepsy. Subjects were recorded both in baseline conditions and after chronic vagus nerve stimulation. Sleep parameters of the entire night were evaluated. Mean power value of slow-wave activity was computed in the first non-rapid… Mehr anzeigen

Our study aimed to evaluate the existence and entity of changes in sleep structure following vagus nerve stimulation in patients with refractory epilepsy.
METHOD:

A polysomnographic study was performed on the nocturnal sleep of 10 subjects with refractory epilepsy. Subjects were recorded both in baseline conditions and after chronic vagus nerve stimulation. Sleep parameters of the entire night were evaluated. Mean power value of slow-wave activity was computed in the first non-rapid eye movement sleep cycle. A sleep-wake diary evaluated quantity of both nocturnal and daytime sleep, while visual-analog scales assessed quality of sleep and wake. The differences between the 2 conditions underwent parametric and nonparametric statistical evaluation.
RESULTS:

Vagus nerve stimulation produced a significant reduction in REM sleep (in all subjects with vagus nerve stimulus intensity greater than 1.5 milliampere, but not in the only patient with a stimulus intensity less than 1.5 milliampere), along with an increase in the number of awakenings, percentage of wake after sleep onset, and stage 1 sleep. Data from a sleep-wake questionnaire show a decrease in both nocturnal sleep and daytime naps and an increased daytime alertness, while the quality of wakefulness is globally improved. Spectral analysis shows an enhancement of delta power during non-rapid eye movement sleep.
CONCLUSIONS:

Our data demonstrate major effects of vagus nerve stimulation on both daytime alertness (which is improved) and nocturnal rapid eye movement sleep (which is reduced). These effects could be interpreted as the result of a destabilizing action of vagus nerve stimulation on neural structures regulating sleep-wake and rapid eye movement/non-rapid eye movement sleep cycles. Lower intensity vagus nerve stimulation seems only to improve alertness; higher intensity vagus nerve stimulation seems able to exert an adjunctive rapid eye movement sleep-attenuating effect. Weniger anzeigen

Book on physiology of sleep and sleep disorders

Under particular conditions a patent foramen ovale (PFO) can potentially give rise to ischemic stroke by means of paradoxic embolization. In obstructive sleep apnea syndrome (OSAS) right to left shunting (RLSh) can occur through PFO during periods of nocturnal apnea. Our study aimed to evaluate the prevalence of PFO diagnosed by means of transcranial Doppler (TcD) in subjects with OSAS.
METHODS:

Seventy-eight consecutive subjects with OSAS (mean age 53+/-12 years) and 89 normal… Mehr anzeigen

Under particular conditions a patent foramen ovale (PFO) can potentially give rise to ischemic stroke by means of paradoxic embolization. In obstructive sleep apnea syndrome (OSAS) right to left shunting (RLSh) can occur through PFO during periods of nocturnal apnea. Our study aimed to evaluate the prevalence of PFO diagnosed by means of transcranial Doppler (TcD) in subjects with OSAS.
METHODS:

Seventy-eight consecutive subjects with OSAS (mean age 53+/-12 years) and 89 normal controls (mean age 48+/-9 years) underwent TcD with intravenous application of agitated physiological saline solution. The test was performed on patients at rest and during Valsalva maneuver.
RESULTS:

PFO was present in 21 out of 78 patients with OSA (27%) and in 13 out of 89 control patients (15%). Seventeen out of 21 patients with OSA showed PFO only during Valsalva maneuver (85%) with respect to 12 out of 13 subjects of the control group (92%). Prevalence of PFO in OSAS was statistically different with respect to the control group (P<0.05). However, no statistically significant differences could be found for the prevalence of provocative-only shunting PFO with respect to already at rest shunting PFO in patients with OSAS with respect to the control group.
CONCLUSIONS:

Prevalence of PFO in subjects with OSA is significantly higher than in normal controls. The shunt is frequently present only during Valsalva maneuver. Weniger anzeigen

OBJECTIVE:

Experimental and clinical evidence in prion diseases suggests that the prion protein gene (PRNP) plays a role in regulating sleep.
METHODS:

Seventeen healthy individuals belonging to a single fatal familial insomnia pedigree, 8 carriers and 9 non-carriers of the PRNP codon 178 mutation, underwent polysomnography and spectral electroencephalographic (EEG) analysis. All were also characterized with regard to the codon 129 polymorphism on both PRNP… Mehr anzeigen

OBJECTIVE:

Experimental and clinical evidence in prion diseases suggests that the prion protein gene (PRNP) plays a role in regulating sleep.
METHODS:

Seventeen healthy individuals belonging to a single fatal familial insomnia pedigree, 8 carriers and 9 non-carriers of the PRNP codon 178 mutation, underwent polysomnography and spectral electroencephalographic (EEG) analysis. All were also characterized with regard to the codon 129 polymorphism on both PRNP alleles.
RESULTS:

PRNP codon 129 polymorphism exhibited influences on sleep-EEG activities. In particular, spindle frequency band power and balance between delta and spindle activity were found to correlate with the genotype of PRNP codon 129, irrespective of the mutation at codon 178.
CONCLUSIONS:

Our data suggest that PRNP codon 129 polymorphism may also affect sleep in the healthy population and warrant further studies in the general population and other sleep disorders. Weniger anzeigen

Acetylcholine (ACh) function is thought not only to play a significant role in memory, learning and other cognitive processes, but studies at a cellular level and in vivo indicate an important role for ACh in vision as well, especially for visual information processing. A suitable experimental model of geriatric memory impairment and Alzheimer dementia that pharmacologically blocks the brain muscarinic transmission has been proposed. This model has been extensively used also as an attempt to… Mehr anzeigen

Acetylcholine (ACh) function is thought not only to play a significant role in memory, learning and other cognitive processes, but studies at a cellular level and in vivo indicate an important role for ACh in vision as well, especially for visual information processing. A suitable experimental model of geriatric memory impairment and Alzheimer dementia that pharmacologically blocks the brain muscarinic transmission has been proposed. This model has been extensively used also as an attempt to test cholinergic drugs in the absence of detailed knowledge of sites and mechanisms of ACh action and as test condition in the investigation of the role of ACh in visual information processing. Alzheimer's dementia results from complex neuron alterations, rather than simply reflecting ACh impoverishment, also involving the visual system, with substantial loss of retinal ganglion cells and alterations in visual information processing. Viewing all these data as a whole, nonspecific ACh actions on cognition, such as arousal or attention, contribute in modulating the function-specific action of ACh in information processing, both at cognitive and visual level. Weniger anzeigen