The clinical use of the MSLT and MWT

The studies examined in this review indicate that the MSL is sensitive to conditions expected to increase sleepiness. MSL are generally lower following sleep loss, following use of sedating medications, during wakefulness in the late night or early morning hours, and among patients with sleep disorders associated with excessive sleepiness such as narcolepsy or obstructive sleep apnea. However, the wide range in MSL makes it difficult to establish a specific threshold value for excessive sleepiness or to discriminate patients with sleep disorders from non-patients. Some of this variation may be attributable to methodological differences and some may be attributable to individual differences in sleep tendency (e.g., related to age). The studies analyzed in this review indicate that the MSL on both the MSLT and MWT does not discriminate well between patients with sleep disorders and normal populations. This is due to large SD as well as floor or ceiling effects in the tests. However, the MSL shows appropriate change from initial testing to subsequent testing following treatment or manipulations intended to alter sleepiness or alertness. Additionally the presence of two or more SOREMPs on the MSLT is a common finding in narcolepsy patients. However, SOREMPs are not exclusive to narcolepsy patients but are frequent in untreated sleep apnea     

Daytime Sleepiness and Driving Performance in Patients with Obstructive Sleep Apnea: Comparison of the MSLT,the MWT,and a Simulated Driving Task

Study Objectives:

To test the reliability of a driving-simulation test for the objective measurement of daytime alertness compared with the Multiple Sleep Latency Test (MSLT) and with the Maintenance of Wakefulness Test (MWT), and to test the ability to drive safely, in comparison with on-road history, in the clinical setting of untreated severe obstructive sleep apnea.

Design:

N/A.

Setting:

Sleep laboratory.

Patients or Participants:

Twenty-four patients with severe obstructive sleep apnea and reported daytime sleepiness varying in severity (as measured by the Epworth Sleepiness Scale).

Interventions:

N/A.

Measurements and Results:

Patients underwent MSLT and MWT coupled with 4 sessions of driving-simulation test on 2 different days randomly distributed 1 week apart. Simulated-driving performance (in terms of lane-position variability and crash occurrence) was correlated with sleep latency on the MSLT and more significantly on the MWT, showing a predictive validity toward the detection of sleepy versus alert patients with obstructive sleep apnea. In addition, patients reporting excessive daytime sleepiness or a history of car crashes showed poorer performances on the driving simulator.

Conclusions:

A simulated driving test is a suitable tool for objective measurement of daytime alertness in patients with obstructive sleep apnea. Further studies are needed to clarify the association between simulated-driving performance and on-road crash risk of patients with sleep disordered breathing.

Citation:

Pizza F; Contardi S; Mondini S; Trentin L; Cirignotta F. Daytime sleepiness and driving performance in patients with obstructive sleep apnea: comparison of the MSLT, the MWT, and a simulated driving task. SLEEP 2009;32(3):382-391.     

Lymphocytes which differentiate in an allogeneic thymus

Nude mice which have been grafted with an allogeneic H-2-incompatible thymus are frequently specifically tolerant to skin grafts from the thymus donor strain. The evidence presented here indicates that both clonal deletion and peripheral suppressor cells play a part in maintaining this tolerance.     

Test-retest reliability of the MSLT

The test-retest reliability of the Multiple Sleep Latency Test (MSLT) was evaluated in 14 healthy normal subjects. Each slept a single night in the laboratory (8 h time in bed) and received the MSLT the following day (1000, 1200, 1400, and 1600 h) on two occasions separated by 4-14 months. Mean sleep latency (four tests) was highly reliable from MSLT to MSLT (r = 0.97, p less than 0.001). The test-retest reliability did not change as a function of the interval of time between tests or as a function of the level of sleepiness (range = 4-20 min) within the population. However, as the number of tests comprising the MSLT was reduced below three, the reliability was reduced such that only 50% or less of the variance could be predicted.     

Simple color tests based on an alanyl peptidase reaction which differentiate Listeria monocytogenes from other Listeria species.

The hydrolysis of DL-alanine-beta-naphthylamide and D-alanine-p-nitroanilide for identification of Listeria spp. has been studied with 227 cultures. All species of Listeria, except L. monocytogenes, hydrolyzed these substrates. The reactions were detected by simple chromogenic reactions and could substitute for the CAMP test.     

Activity, arousal, and the MSLT in patients with insomnia

OBJECTIVES: It has recently been shown that physiological arousal following walking increased sleep latencies during daytime naps as compared to sleep latencies following TV viewing. Patients with insomnia have been shown to have increased physiological arousal and to also have longer MSLT latencies. It was hypothesized that insomnia patients, who are at a higher state of physiological arousal, would be unable to relax while lying in bed and watching TV and therefore would have relatively longer sleep latencies in naps following TV watching (due to inability to relax) as compared to walking. DESIGN: Twelve patients with psychophysiological insomnia took Multiple Sleep Latency Tests after either watching television for 15 minutes or after a 5-minute walk following baseline, sleep deprivation, and recovery sleep conditions. SETTING: Sleep Laboratory PATIENTS: Twelve patients with psychophysiological insomnia INTERVENTIONS: Manipulation of state arousal and sleep deprivation RESULTS: Sleep latencies were significantly longer following the walk as compared to watching TV (11.9 vs. 6.9 min. respectively). Sleep latencies were 13.4 and 3.8 min. following baseline and sleep deprivation conditions. Heart period, used as a measure of physiological arousal, was significantly elevated throughout naps following the walk as compared to naps following TV viewing. Heart period was also significantly correlated with nap sleep latency. CONCLUSIONS: The insomnia patients in this study had significantly increased arousal, as measured by heart rate, and significantly longer sleep latencies after walking as compared to resting. The magnitude of these changes was similar to that seen in normal subjects in a previous study. These data, in concert with previous work, support the contention that measured sleep tendency is a combination of sleep drive and level of central nervous system arousal, where arousal has both state and trait components.     

Brain ERP components predict which individuals progress to Alzheimer's disease and which do not

Predicting which individuals will progress to Alzheimer's disease (AD) is important in both clinical and research settings. We used brain Event-Related Potentials (ERPs) obtained in a perceptual/cognitive paradigm with various processing demands to predict which individual Mild Cognitive Impairment (MCI) subjects will develop AD versus which will not. ERP components, including P3, memory “storage” component, and other earlier and later components, were identified and measured by Principal Components Analysis. When measured for particular task conditions, a weighted set of eight ERP component_conditions performed well in discriminant analysis at predicting later AD progression with good accuracy, sensitivity, and specificity. The predictions for most individuals (79%) had high posterior probabilities and were accurate (88%). This method, supported by a cross-validation where the prediction accuracy was 70-78%, features the posterior probability for each individual as a method of determining the likelihood of progression to AD. Empirically obtained prediction accuracies rose to 94% when the computed posterior probabilities for individuals were 0.90 or higher (which was found for 40% of our MCI sample).     

Mechanisms by which extracellular matrix components induce osteoblast apoptosis

Bone cell apoptosis is seen at sites of active turnover. We hypothesize that at these sites, factors released from resorbing bone induce apoptosis of vicinal cells. Related to this observation, earlier studies indicate that an elevation in the level of inorganic phosphate ions combined with a modest increase in the calcium (Ca2+) concentration, or a rise in the local concentration of RGD-containing peptides promote osteoblast apoptosis. The aim of the current investigation is to elucidate the mechanism by which these extracellular matrix components induce bone cell apoptosis. The data presented in this study clearly demonstrate that osteoblasts are sensitive to peptide fragments and solubilized mineral ions. It is reasonable to expect that these apoptogens would be generated by osteoclasts during resorption of the extracellular bone matrix. We suggest that these components conspire to regulate bone cell function. In terms of the mechanism by which these agents activate apoptosis, it is clear that while they share common pathways, there are some differences in the mechanism of apoptosis. These differences appear to be upstream of caspase activation. The observation that two such pathways exist lends strength to the notion that apoptosis is carefully regulated in bone and that signals from both matrix components act together to trigger the remodeling process.     

Arousal from sleep: the differential effect of frequencies equated for loudness

The present research required individual subjects to personally equate the loudness of three different auditory frequencies. When these same auditory stimuli were presented to the subject during sleep they produced equal levels of arousal (increases in cortical desynchronization) during sleep characterized by nonREM fast-wave EEG activity but different levels of arousal during sleep characterized by slow-wave EEG activity. During this latter type of sleep, the individual's arousal appeared more related to physical sound pressure level than subjective loudness. These results are discussed in relation to the possible occurrence of cortical inhibition during sleep characterized by slow-wave electrocortical activity.     

Plasma components which mediate cellular defences in the gastropod mollusc Biomphalaria glabrata

Blood plasmas from certain strains of Biomphalaria glabrata are known to have components which facilitate a hemocyte-effected cytotoxic response against encapsulated Schistosoma mansoni sporocysts. The possible identity of the factor(s) has been investigated. Sporocysts placed in snail plasma rapidly acquire a wide variety of host plasma antigens, at least some of which are displayed on the parasite surface. Plasmas from strains of snail resistant to the parasite agglutinate fixed sporocysts, while plasmas from susceptible strains fail to do so. Fixed sporocysts incubated in plasma bind selectively a subpopulation of plasma antigens; some are bound uniquely in resistant plasma. Another resembles a hemagglutinin from snail plasma. These and other recently acquired data are discussed in light of increasing evidence for defensive roles of multivalent lectins.     

Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the epworth sleepiness scale: failure of the MSLT as a gold standard

Excessive daytime sleepiness (EDS) is an important symptom that needs to be quantified, but there is confusion over the best way to do this. Three of the most commonly used tests: the multiple sleep latency test (MSLT), the maintenance of wakefulness test (MWT) and the Epworth sleepiness scale (ESS) give results that are significantly correlated in a statistical sense, but are not closely related. The purpose of this investigation was to help clarify this problem. Previously published data from several investigations were used to calculate the reference range of normal values for each test, defined by the mean+/-2 SD or by the 2.5 and 97.5 percentiles. The 'rule of thumb' that many people rely on to interpret MSLT results is shown here to be misleading. Previously published results from each test were also available for narcoleptic patients who were drug-free at the time and who by definition had EDS. This enabled the sensitivity and specificity of the three tests to be compared for the first time, in their ability to distinguish the EDS of narcolepsy from the daytime sleepiness of normal subjects. The receiver operator characteristic curves clearly showed that the ESS is the most discriminating test, the MWT is next best and the MSLT the least discriminating test of daytime sleepiness. The MSLT can no longer be considered the gold standard for such tests.     

体外诱导恒河猴骨髓基质细胞分化为神经细胞的分化条件

目的比较血清维甲酸(retinoic acid,RA)、胶质细胞源神经营养因子(glial cell line-derived neurotrophic factor,GDNF)及脑源性神经营养因子(brain derived neurotrophic factor,BDNF)等在不同浓度诱导条件下使恒河猴骨髓基质细胞(bone marrow stromal cells)诱导分化为神经干细胞(NSCs)及成熟神经细胞的分化条件。方法用Nestin、CD133抗体免疫细胞化学染色,鉴定NSCs;用NSE、β-tublin鉴定神经元;用GFAP鉴定神经胶质细胞,膜片钳检测分化成熟细胞的电生理特性。结果培养第8天多数细胞表现出Nestin及CD133抗原阳性,即为NSCs细胞;诱导后3天即有神经元样细胞出现,此后神经元样细胞逐渐增多,膜片钳检测发现这些细胞具有类似神经细胞的电生理特性。同时,与其他培养条件相比较,低浓度血清(2．5％) RA GDNF组诱导分化效能最高。结论应用RA GDNF及配合使用低浓度血清能够高效诱导骨髓源NSCs向成熟神经细胞分化。     

How does Japan differentiate hyperplasia from neoplasia?

A Japanese pathologist's contribution to the discussion of the problem on differentiation of hyperplasia from neoplasia is to introduce his experience and knowledge in human and experimental pathology of gastric, hepatic, and uterine cervical cancers, all of which are prevalent in Japan. Canine and rodent gastric cancers induced experimentally by N-ethyl-N'-nitro-N-nitrosoguanidine or N-methyl-N'-nitro-N-nitrosoguanidine, respectively, show different histologic types which are similar to human gastric cancer when examined routinely by endoscopic method. Dogs show more similarities to human gastric cancer than rats in the morphologic features and responses to chemotherapy. Serial liver biopsies performed on patients with liver diseases revealed the final stages of liver cell carcinoma in some of them. They all progressed to liver cirrhosis before terminating in carcinoma. However, this does not mean that the hyperplastic nodule is an obligatory precursor of carcinoma in human. Among experimental models of liver cancer produced by a large number of agents, only carbon tetrachloride and luteoskyrin seem to induce liver cell carcinoma combined with cirrhotic lesions in rodents. The mode of manifestation of atypical changes in the proliferating cells as preneoplastic or neoplastic lesions seems to differ according to tissue. The cellular pathology of cervicovaginal smears is a reliable index for detection of carcinoma in the cervix, where the appearance of atypical cells represents a landmark between benign and malignant tumors.     

Female Sexual Arousal and the Menstrual Cycle

Abstract

Self-reports of sexual arousal were significantly affected by conditions under which they were elicited. Such self-reports in women not taking oral contraceptives were congruent with a hormonal basis for such arousal only when the women were “unaware” that the study investigated sexual arousal as a function of the menstrual cycle. The “unaware” condition was operationalized by means of daily self-reports elicited from males and females for 11 weeks under the guise of a study of biological rhythms. A composite of one to three menstrual cycles for 26 women not taking oral contraceptives showed that sexual arousal during the luteal phase, when progesterone is relatively high, was significantly lower compared to peaks around ovulation, and premenstrual and late menstrual days (p<.02). For the “aware” condition, women were asked to remember moods for the premenstrual, menstruating and luteal phases of the very last cycle on which they had just finished giving “unaware” daily self-reports. A 2 × 3 analysis of variance (with “aware” versus “unaware” conditions and premenstrual, menstruating, and luteal phases of the last cycle as the two independent variables) yielded a significant interaction effect with F=6.5, df=2, 50, p<.003. In the “unaware” condition, sexual arousal was reported lowest during the luteal phase. The opposite pattern was reported in the “aware” condition. The results suggest that cyclical variability may not be simply due to women's misattribulions. However, “awareness” has an effect on self-report measures and may bias reports according to cultural stereotypes. Daily self-reports of sexual arousal for men were averaged over the duration of the study. This average was 3.16. The equivalent average for women not taking oral contraceptives was 2.35 and for women taking oral contraceptives was 2.62. Analysis of variance of these three means yielded a significant difference with F=4.49, df=2, 59, p<.02.     

Arousal response to hypoxia in newborns: Insights from animal models

In newborns, the inability to initiate an arousal response to hypoxia is associated with apnea of prematurity, sudden infant death syndrome, and rare genetic disorders of respiratory control. Despite intensive research, the mechanisms of this response are poorly understood. This paper provides an overview of studies investigating the arousal response to hypoxia, with special emphasis on newborn mouse models. Mutant mouse models can provide valuable information regarding the pathogenesis of genetically determined disorders affecting arousal response to hypoxia, although data remain sparse. In mice, the arousal response to hypoxia emerges immediately after birth, when the ventilatory response to hypoxia is still immature. Habituation of the arousal response occurs after repeated hypoxic episodes. Newborn mice can learn to associate novel odors to hypoxia and respond to those odors by producing alerting responses, suggesting that the arousal response to hypoxia may be shaped by learning processes.     

Discharge Patterns of Human Genioglossus Motor Units during Arousal from Sleep

Study Objectives:

Single motor unit recordings of the human genioglossus muscle reveal motor units with a variety of discharge patterns. Integrated multiunit electromyographic recordings of genioglossus have demonstrated an abrupt increase in the muscle''s activity at arousal from sleep. The aim of the present study was to determine the effect of arousal from sleep on the activity of individual motor units as a function of their particular discharge pattern.

Design:

Genioglossus activity was measured using intramuscular fine-wire electrodes inserted via a percutaneous approach. Arousals from sleep were identified using the ASDA criterion and the genioglossus electromyogram recordings analyzed for single motor unit activity.

Setting:

Sleep research laboratory.

Participants:

Sleep and respiratory data were collected in 8 healthy subjects (6 men).

Measurements and Results:

138 motor units were identified during prearousalarousal sleep: 25% inspiratory phasic, 33% inspiratory tonic, 4% expiratory phasic, 3% expiratory tonic, and 35% tonic. At arousal from sleep inspiratory phasic units significantly increased the proportion of a breath over which they were active, but did not appreciably increase their rate of firing. 80 new units were identified at arousals, 75% were inspiratory, many of which were active for only 1 or 2 breaths. 22% of units active before arousal, particularly expiratory and tonic units, stopped at the arousal.

Conclusions:

Increased genioglossus muscle activity at arousal from sleep is primarily due to recruitment of inspiratory phasic motor units. Further, activity within the genioglossus motoneuron pool is reorganized at arousal as, in addition to recruitment, ∼20% of units active before arousals stopped firing.

Citation:

Wilkinson V; Malhotra A; Nicholas CL; Worsnop C; Jordan AS; Butler JE; Saboisky JP; Gandevia SC; White DP; Trinder J. Discharge patterns of human genioglossus motor units during arousal from sleep. SLEEP 2010;33(3):379-387.