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Allan I Pack

Publications and source records attributed to Allan I Pack.

At least 37 records · Page 2Linked to original sources
PubMed2005

Changes in symptoms of sleep-disordered breathing during pregnancy.

BACKGROUND: Although incident snoring is common in pregnant women and has been proposed as a potential risk factor for adverse maternal-fetal outcomes, the development of sleep-disordered breathing during pregnancy has not been prospectively described. METHODS: Using the Apnea Symptom Score from the Multivariable Apnea Prediction Index and the Epworth Sleepiness Scale, we prospectively assessed symptoms of sleep-disordered breathing and daytime somnolence in 155 women to determine whether symptoms increased during pregnancy and the characteristics associated with increasing symptoms. RESULTS: We found that sleep-disordered breathing symptoms (Apnea Symptom Score, 0.44 (SEM 0.58) vs 0.95 (0.09, P < .001) and the degree of daytime somnolence (Epworth Sleepiness Scale, 8.6 (0.3) vs 10.2 (0.4), P = .0003) increased significantly during pregnancy. Women with higher baseline body mass indexes and greater increases in neck circumference during pregnancy reported higher apnea symptom scores. Of the 155 subjects, 11.4% reported an increase in Apnea Symptom Score of 2 units or more, consistent with a clinically significant increase in symptoms; these women experienced a significantly greater increase in subjective sleepiness than other subjects (P = .03). Excessive daytime somnolence (Epworth Sleepiness Scale > 10) was prevalent throughout pregnancy (31.0%-45.5%). CONCLUSIONS: Our data demonstrate that symptoms of sleep-disordered breathing increase during pregnancy and that more than 10% of our subjects may be at risk for developing sleep apnea during pregnancy. Excessive daytime somnolence was highly prevalent even early in pregnancy and became increasingly common as pregnancy progressed.

Adult↗
PubMed2005

Sleep deprivation induces the unfolded protein response in mouse cerebral cortex.

Little is known about the molecular mechanisms underlying sleep. We show the induction of key regulatory proteins in a cellular protective pathway, the unfolded protein response (UPR), following 6 h of induced wakefulness. Using C57/B6 male mice maintained on a 12:12 light/dark cycle, we examined, in cerebral cortex, the effect of different durations of prolonged wakefulness (0, 3, 6, 9 and 12 h) from the beginning of the lights-on inactivity period, on the protein expression of BiP/GRP78, a chaperone and classical UPR marker. BiP/GRP78 expression is increased with increasing durations of sleep deprivation (6, 9 and 12 h). There is no change in BiP/GRP78 levels in handling control experiments carried out during the lights-off period. PERK, the transmembrane kinase responsible for attenuating protein synthesis, which is negatively regulated by binding to BiP/GRP78, is activated by dissociation from BiP/GRP78 and by autophosphorylation. There is phosphorylation of the elongation initiation factor 2alpha and alteration in ribosomal function. These changes are first observed after 6 h of induced wakefulness. Thus, prolonging wakefulness beyond a certain duration induces the UPR indicating a physiological limit to wakefulness.

Animals↗
PubMed2005

Claustrophobia and adherence to CPAP treatment.

This study evaluated the effect of claustrophobia, an abnormal dread or fear of closed spaces, on adherence to continuous positive airway pressure (CPAP) therapy. The design was a secondary analysis of data from a prospective study of participants (N = 153) that completed 3 months of CPAP therapy from seven sleep disorders centers in the United States and Canada. A 15-item subscale adapted from the Fear and Avoidance Scale measured claustrophobic tendencies pre-CPAP treatment and again after 3 months. An overt monitor attached to the CPAP machines recorded mask-on CPAP adherence. There was a statistically significant difference in claustrophobia scores by adherence group (< 2 hours, 2 to < 5 hours, > or = 5 hours) and time period (pre-CPAP and after 3 months CPAP). Poor CPAP adherence (< 2 hours per night)was more than two times higher in participants with a claustrophobia score > or = 25. Identification of persons with increased claustrophobia tendencies and targeted interventions may increase adherence.

Adult↗
PubMed2004

Occupational screening for obstructive sleep apnea in commercial drivers.

Excluding the presence of obstructive sleep apnea in commercial drivers is valuable, as the syndrome may increase their risk of sleepiness-related accidents. Using polysomnography as the criterion standard, we prospectively compared accuracies of five strategies in excluding the presence of severe sleep apnea and, secondarily, any sleep apnea among 406 commercial drivers. These strategies were as follows: (1) symptoms; (2) body mass index; (3) symptoms plus body mass index; (4) a two-stage approach with symptoms plus body mass index for everyone, followed by oximetry for a subset; and (5) oximetry for all. For excluding severe apnea, the two-stage strategy was highly successful, with 91% sensitivity and specificity, and a negative likelihood ratio of 0.10. This strategy was comparable in accuracy to oximetry, which had a negative likelihood ratio of 0.12, and was 88% sensitive and 95% specific. If we avoided oximetry altogether, then symptoms together with body mass index were 81% sensitive and 73% specific, with a negative likelihood ratio of 0.26. On the other hand, excluding any apnea could not be done with reasonable accuracy unless oximetry was used. We conclude that two-stage screening is likely to be a viable means of excluding severe sleep apnea among commercial drivers.

Adult↗
PubMed2004

Glycogen in the brain of Drosophila melanogaster: diurnal rhythm and the effect of rest deprivation.

One function of sleep is thought to be the restoration of energy stores in the brain depleted during wakefulness. One such energy store found in mammalian brains is glycogen. Many of the genes involved in glycogen regulation in mammals have also been found in Drosophila melanogaster and rest behavior in Drosophila has recently been shown to have the characteristics of sleep. We therefore examined, in the fly, variation in the glycogen contents of the brain, the whole head and the body throughout the rest/activity cycle and after rest deprivation. Glycogen in the brain varies significantly throughout the day (p=0.001) and is highest during rest and lowest while flies are active. Glycogen levels in the whole head and body do not show diurnal variation. Brain glycogen drops significantly when flies are rest deprived for 3 h (p=0.034) but no significant differences are observed after 6 h of rest deprivation. In contrast, glycogen is significantly depleted in the body after both 3 and 6 h of rest deprivation (p<0.0001 and p<0.0001, respectively). Glycogen in the fly brain changes in relationship to rest and activity and demonstrates a biphasic response to rest deprivation similar to that observed in mammalian astrocytes in culture.

Animals↗
PubMed2003

Functional genomics of sleep.

Functional genomics is a systematic and high-throughput effort to analyze the functions of genes and gene products. Functional genomics is divided into gene- and phenotype-driven approaches. Gene-driven approaches to the functional genomics of sleep have demonstrated that transcripts of many genes change as a function of behavioral state. A phenotype-driven approach includes identification and characterization of gene function through the analyses of natural polygenic traits, creation of transgenic animals or high-throughput mutagenesis. Identification of a gene for narcolepsy through QTL analyses and concomitantly using a transgenic approach is one example of the phenotype-driven approach to the functional genomics of sleep. Though the majority of functional genomics is currently performed in mice, the rat is emerging as an important model for genomic research. Since rest in Drosophila shares many features with mammalian sleep, this allows a comparative functional genomics approach to the study of rest and sleep. The concepts outlined here for the functional genomics of sleep are applicable to respiration research.

Animals↗
PubMed2003

Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging.

We used sophisticated volumetric analysis techniques with magnetic resonance imaging in a case-control design to study the upper airway soft tissue structures in 48 control subjects (apnea-hypopnea index, 2.0 +/- 1.6 events/hour) and 48 patients with sleep apnea (apnea-hypopnea index, 43.8 +/- 25.4 events/hour). Our design used exact matching on sex and ethnicity, frequency matching on age, and statistical control for craniofacial size and visceral neck fat. The data support our a priori hypotheses that the volume of the soft tissue structures surrounding the upper airway is enlarged in patients with sleep apnea and that this enlargement is a significant risk factor for sleep apnea. After covariate adjustments the volume of the lateral pharyngeal walls (p < 0.0001), tongue (p < 0.0001), and total soft tissue (p < 0.0001) was significantly larger in subjects with sleep apnea than in normal subjects. These data also demonstrated, after covariate adjustments, significantly increased risk of sleep apnea the larger the volume of the tongue, lateral pharyngeal walls, and total soft tissue: (1) total lateral pharyngeal wall (odds ratio [OR], 6.01; 95% confidence interval [CI], 2.62-17.14); (2) total tongue (OR, 4.66; 95% CI, 2.31-10.95); and (3) total soft tissue (OR, 6.95; 95% CI, 3.08-19.11). In a multivariable logistic regression analysis the volume of the tongue and lateral walls was shown to independently increase the risk of sleep apnea.

Adult↗
PubMed2003

Genetic evidence for a role of CREB in sustained cortical arousal.

The cyclic AMP-response element binding protein (CREB) is an activity-dependent transcription factor important for synaptic plasticity and memory storage. Levels of phosphorylated CREB within the cortex are higher in waking than in sleep, suggesting that CREB plays a role in sleep/wake regulation in mammals. We tested the hypothesis that CREB is critical for sleep/wake regulation by examining behavioral state parameters in mice lacking the alpha and Delta isoforms of CREB. Over 24 h, time spent awake was significantly decreased in CREB alphaDelta mutant mice by approximately 100 min, and time spent in nonrapid eye movement sleep (NREM) sleep was increased correspondingly. Wake and REM sleep periods were shorter in CREB alphaDelta mice, and CREB alphaDelta mice had decreased levels of -activity during wake and REM sleep, consistent with an impairment in the ability to maintain an activated electroencephalogram. These results suggest that the CREB protein contributes to the mechanisms by which wakefulness is maintained and demonstrate that specific genetic alterations in species as diverse as Drosophila and mice produce similar phenotypes in arousal and wakefulness.

Animals↗
PubMed2003

Modafinil maintains waking in the fruit fly drosophila melanogaster.

Fruit flies exhibit a sleep-like rest state that shares behavioral characteristics with mammalian sleep, including a homeostatic increase in rest after deprivation by mechanical methods. We tested the effect of modafinil, a novel wake-promoting agent, to discover whether its effect is conserved. Flies fed various concentrations of modafinil were compared to groups of control flies fed diluent only. Flies were also tested for a homeostatic response to the modafinil-related rest deprivation by examining rest and activity during recovery after 48H modafinil administration, compared to rest deprivation alone and to both treatments combined. The duration and consolidation of rest, and the duration, intensity, and circadian rhythms of activity were measured. Modafinil significantly and dose-dependently decreased rest when fed at concentrations from 2.5 mg/ml to 0.3125 mg/ml. Activity intensity was not increased, and circadian timing was unchanged, although the 2.5 mg/ml dose blunted the amplitude of overt circadian locomotor rhythms. Compared to controls, the duration of rest bouts was decreased in flies fed 2.5 mg/ml, and waking was frequently interrupted by 5-min periods of immobility. A rest rebound (significant increase in rest) followed withdrawal of either 2.5mg/ml or 0.625mg/ml modafinil after 48H. When directly compared to 6H total rest deprivation, the increase after withdrawal was briefer, reminiscent of the attenuated rest rebound seen in mammals, including humans, after modafinil. However, modafinil withdrawal combined with 6H total rest deprivation significantly enhanced the rebound, suggesting that a rest debt is accumulating during modafinil. We conclude that modafinil affects states of arousal in Drosophila in the same direction as it does in mammals. This discovery provides a tool for searching for conserved molecular mechanisms by which modafinil regulates rest and waking.

Animals↗
PubMed2003

Functional outcomes of excessive daytime sleepiness in older adults.

OBJECTIVES: To describe the effect of self-reported excessive daytime sleepiness (EDS) on functional outcomes. DESIGN: Case-control study designed to examine differences in functional status between cases (with daytime sleepiness) and controls (no daytime sleepiness) with regard to demographic factors, general health, sleep history, and medications. SETTING: Retirement communities in southeastern Pennsylvania, Delaware, and New Jersey. PARTICIPANTS: Seventy-six nondepressed, nondemented adults, aged 65 and older, were cases (had daytime sleepiness) and 38 were controls (had no daytime sleepiness). MEASUREMENTS: Standardized questionnaires to assess disease-specific functional status (Functional Outcomes of Sleepiness Questionnaire (FOSQ) and Epworth Sleepiness Scale (ESS)), depression (Geriatric Depression Scale-Short Form and the Center for Epidemiologic Studies-Depression Scale), dementia (Short Blessed Test), demographic factors, current medical history, and sleep complaints. RESULTS: There was a significant difference in functional status between sleepy cases and nonsleepy controls. Sleepiness had a moderate to large negative effect (effect size range from 0.59 to 0.83, P <.005) on the following functional domains of the FOSQ: social outcome, general productivity, vigilance, activity level, and global assessment of functional status. Correlation between ESS and FOSQ subscales were -0.31 to -0.67, P <.05. Examination of cases with daytime sleepiness revealed increased functional impairment in individuals with more than three medical conditions or those taking more than four medications (P <.001 and P =.03, respectively). CONCLUSION: Daytime sleepiness is associated with functional impairments in a broad range of activities. The decrease in daily functioning noted in the sleepy subjects has implications for deconditioning and related comorbidity. These findings suggest that exploration of daytime sleepiness should be part of the ongoing assessment of the elderly, particularly those with multiple medical conditions.

Activities of Daily Living↗
PubMed2003

The validity and feasibility of saliva melatonin assessment in the elderly.

Recent work in young and middle-aged subjects suggests that melatonin levels in saliva may represent a viable alternative to serum melatonin measurement. We hypothesized that it may be a valid measure of melatonin levels in older adults as well, but features unique to the elderly may limit its utility. To study this, subjects were admitted to an academic medical center where saliva and serum specimens were collected concurrently in dim light conditions during a 14-hr overnight study period and analyzed for melatonin levels with radioimmunoassays (RIAs). Eighty-five subjects over the age of 65 with a broad range of medical conditions participated in the study. Subjects with dementia, depression and anemia were excluded. We found that saliva volume was inadequate for analysis (<200 microL) in 23.6% of specimens, with the majority of inadequate volume specimens occurring after midnight and inadequate specimens occurring more frequently in females than in males. The correlation coefficient for saliva melatonin and serum melatonin was r = 0.659 (Spearman, P < 0.001), and r = 0.466 for saliva dim light melatonin onset (DLMO) and serum DLMO. Saliva melatonin levels were 30.9% of serum melatonin levels, with a wide range of ratios noted between subjects. Overall melatonin levels influenced both the correlation and ratio of saliva melatonin to serum melatonin; higher correlations and lower ratios were noted when melatonin levels were high. Saliva specimens provide an economical and practical method for melatonin assessment, however, in older adults, issues such as hyposalivation and low melatonin levels limit the feasibility and validity, respectively, of saliva melatonin.

Aged↗
PubMed2003

Enzymes of adenosine metabolism in the brain: diurnal rhythm and the effect of sleep deprivation.

Adenosine plays a role in promoting sleep, an effect that is thought to be mediated in the basal forebrain. Adenosine levels vary in this region with prolonged wakefulness in a unique way. The basis for this is unknown. We examined, in rats, the activity of the major metabolic enzymes for adenosine - adenosine deaminase, adenosine kinase, ecto- and cytosolic 5'-nucleotidase - in sleep/wake regulatory regions as well as cerebral cortex, and how the activity varies across the day and with sleep deprivation. There were robust spatial differences for the activity of adenosine deaminase, adenosine kinase, and cytosolic and ecto-5'-nucleotidase. However, the basal forebrain was not different from other sleep/wake regulatory regions apart from the tuberomammillary nucleus. All adenosine metabolic enzymes exhibited diurnal variations in their activity, albeit not in all brain regions. Activity of adenosine deaminase increased during the active period in the ventrolateral pre-optic area but decreased significantly in the basal forebrain. Enzymatic activity of adenosine kinase and cytosolic-5'-nucleotidase was higher during the active period in all brain regions tested. However, the activity of ecto-5'-nucleotidase was augmented during the active period only in the cerebral cortex. This diurnal variation may play a role in the regulation of adenosine in relationship to sleep and wakefulness across the day. In contrast, we found no changes specifically with sleep deprivation in the activity of any enzyme in any brain region. Thus, changes in adenosine with sleep deprivation are not a consequence of alterations in adenosine enzyme activity.

5'-Nucleotidase↗
PubMed2003

Self-efficacy in sleep apnea: instrument development and patient perceptions of obstructive sleep apnea risk, treatment benefit, and volition to use continuous positive airway pressure.

STUDY OBJECTIVES: The purpose of this study was to evaluate the Self-Efficacy Measure for Sleep Apnea (SEMSA) designed to assess adherence-related cognitions. DESIGN: Subjects completed the questionnaire prior to the initiation of continuous positive airway pressure (CPAP) treatment. Test-retest reliability of the instrument was evaluated by having a subset of subjects complete the SEMSA a second time at home, 1 week later, returning the questionnaire by mail. PATIENTS: 213 subjects with newly diagnosed obstructive sleep apnea were recruited from the clinic populations of 2 sleep disorders centers. MEASUREMENTS AND RESULTS: Content validity was confirmed by a panel of expert judges. Confirmatory factor analysis validated the 3 a priori sub-scales: risk perception, outcome expectancies, and treatment self-efficacy. The internal consistency of the total instrument was 0.92. Test-retest reliability coefficients (N = 20) were estimated to be 0.68, P = 0.001, for Perceived Risk; 0.77, P more more than 0.0001, for Outcome Expectancies; and 0.71, P = 0.0005, for the Treatment Self-Efficacy subscale. Subject responses indicated that approximately half of the subjects did not perceive problems with concentration, sexual performance, sleepy driving, or an accident as related to sleep apnea. More than 60% of the subjects acknowledged most of the benefits of CPAP presented to them, but only 53% associated CPAP use with enhanced sexual performance. Frequently identified barriers to treatment use were nasal stuffiness, claustrophobia, and disturbing bed partner sleep. CONCLUSION: These findings indicate that the SEMSA has strong psychometric properties and has the potential for identifying patient perceptions that may indicate those most likely to not adhere to treatment.

Adult↗
PubMed2002

Upper airway size analysis by magnetic resonance imaging of children with obstructive sleep apnea syndrome.

Detailed analysis of the upper airway has not been performed in children with obstructive sleep apnea. We used magnetic resonance imaging and automatic segmentation to delineate the upper airway in 20 children with obstructive sleep apnea and in 20 control subjects (age, 3.7 +/- 1.4 versus 3.9 +/- 1.7 years, respectively). We measured mean and minimal cross-sectional area, length, and volume of: (1) the total airway; (2) regions along the adenoid, tonsils, and where adenoid and tonsils overlap; and (3) 10 segments at 10% increments along the airway. The mean cross-sectional area of the total airway of the obstructive sleep apnea group was significantly smaller in comparison with the control group, 28.1 +/- 12.6 versus 47.1 +/- 18.2 mm2, respectively (p < 0.0005). Minimal cross-sectional area and airway volume were smaller in this group, 4.6 +/- 3.3 versus 15.7 +/- 12.7 mm2 (p < 0.0005), and 1,129 +/- 515 versus 1,794 +/- 846 mm3 (p < 0.005), respectively. Regional analysis suggested that the upper airway in children with obstructive sleep apnea is most restricted where adenoid and tonsils overlap. Segmental analysis demonstrated that the upper airway is restricted throughout the initial two-thirds of its length and that the narrowing is not in a discrete region adjacent to either the adenoid or tonsils, but rather in a continuous fashion along both.

Child↗