SLEEP

Hansen, Michael K.; Krueger, James M.

doi: 10.1093/sleep/22.6.707pmid: N/A

SummaryThe liver Kupffer cells constitute the largest population of fixed macrophages in the body and reside at a strategic position in liver sinusoids to interact with mediators from the gut. Previously, we showed that cafeteria feeding increases sleep by a sub-diaphragmatic mechanism and increases interleukin-1β (IL-1β) mRNA expression in rat liver and brain. Thus, the aim of the present experiment was to test the hypothesis that macrophages, in particular liver Kupffer cells, contribute to the excess sleep observed in cafeteria diet fed rats. Sleep-wake activity and brain temperature (Tbr) were examined in rats injected with gadolinium chloride (GdCl3) alone and in rats fed a cafeteria diet with or without prior pretreatment with GdCl3. The intravenous administration of GdCl3 alone, using a dose that blocks phagocytosis and eliminates large Kupffer cells (7.5 mg/kg), increased sleep in the dark period of the light-dark cycle and decreased sleep in the light period. Sleep-wake activity returned to baseline levels 24 h after the injection. In control rats, cafeteria feeding increased non-rapid eye movement sleep (NREMS) and Tbr, and decreased rapid eye movement sleep (REMS) and electroencephalographic slow-wave activity (SWA) during NREMS. GdCl3 pretreatment prevented the increase in NREMS, but did not significantly affect REMS, Tbr, or SWA during NREMS compared with the control rats. These results suggest that liver Kupffer cells contribute to the excess NREMS that accompanies increased feeding possibly via their capacity to produce IL-1β.

Chiu, Helen FK; Leung, Tony; Lam, Linda CW; Wing, Y K; Chung, Dicky WS; Li, SW; Chi, Iris; Law, WT; Boey, KW

doi: 10.1093/sleep/22.6.717pmid: 10505817

AbstractBackground:To examine the sleep habits and one-year prevalence of sleep disturbance (difficulty in falling asleep, broken sleep and early morning wakening) as well as insomnia (subjectively inadequate or poor sleep) in an elderly Chinese population in Hong Kong.Method:In Phase 1, a representative sample of elderly aged 70 years or above were interviewed with a sleep questionnaire, and Cantonese versions of the Mini-Mental State Examination (CMMSE) and Geriatric Depression Scale(CGDS). In Phase 2, those with scores suggestive of cognitive impairment on CMMSE or depression on CGDS were interviewed by psychiatrists for making clinical diagnoses according to DSM IV.Results:1,034 elderly were interviewed in Phase 1. Occasional or persistent sleep disturbance were reported by 75% and insomnia in 38.2% of elderly. Slightly less than half of elderly with sleep disturbance complained of insomnia. Advancing age was associated with a higher rate of sleep disturbance while females had a higher rate of insomnia. Factors associated with sleep disturbance and insomnia included poor perceived health, past history of smoking, current depressive disorders, more chronic physical illness, more life events and more somatic complaints. Only 2.8% of the sample had taken sleeping pills within a one -year period.Conclusions:Sleep disturbance and insomnia are two separate but overlapping constructs and should be differentiated. Sleep disturbance is very common in the elderly and may be due to physiological changes with ageing. In contrast, those with a concommitant complaint of insomnia have impaired physical and mental health and may merit more medical attention.

Walsleben, Joyce A.; Norman, Robert G.; Novak, Ronald D.; O'Malley, Edward B.; Rapoport, David M.; Strohl, Kingman P.

doi: 10.1093/sleep/22.6.728pmid: 10505818

AbstractStudy Objectives:We addressed the issue of how commuting affects sleep habits, and its association with general health and potential sleep disorders in individuals on a large, U.S. commuter rail system.Design:Postage-paid mail back questionnaires were distributed to commuters over 6 consecutive weekdays. The questionnaire incorporated previously validated questions regarding sleep habits.Setting:Questionnaires were dispensed at 15 different rail stations.Participants:21,000 commuters accepted the questionnaire.Measurements and results:Data was analyzed by total group and length of commute. A total of 4715 (22%) questionnaires were returned. Over 50% of the sample reported difficulty with sleep and wakefulness while only 3% sought professional help. Sleep apnea was suspected in 4.2% of male and 1% of female respondents and was associated with increased reports of excessive daytime sleepiness, and history of hypertension, diabetes and obesity. Total nocturnal sleep time was significantly less in those subjects with long commutes. Seventy percent of respondents reported napping during the commute. Length of commute was associated with hypertension.Conclusion:Commuting long distances negatively impacts one's ability to capture adequate sleep. Data suggests that there may be significant numbers of respondents with unrecognized sleep disorders which further impact on general health.

Bahammam, Ahmed; Delaive, Kenneth; Ronald, John; Manfreda, Jure; Roos, Les; Kryger, Meir H.

doi: 10.1093/sleep/22.6.740pmid: 10505819

AbstractObjective:To document changes in health care utilization (physician claims and hospitalizations) two years after diagnosis and treatment of patients with OSAS.Design:Prospective observational cohort study.Setting:The study was done in the Canadian Province of Manitoba. OSAS patients were selected from a University-based sleep disorders center. Control subjects were selected from the general population.Patients and controls:There were 344 OSAS patients on whom there was utilization data for the period of the study. They were matched to controls from the general population by gender, age, and geographic location.Measurements and results:The difference in physician claims between the patients and their matched controls two years after diagnosis and treatment ($174±32.4 (SE) per year in Canadian dollars) was significantly less than the difference in the year before diagnosis ($260±35.7 (SE), p=0.038). Examining the subgroups of patients adhering (PAT) or not adhering (PNAT) to treatment revealed that the changes were only significant in the patients adhering to treatment. Hospital stays for the entire OSAS group decreased from 1.27 days+0.25(SE) per patient per year one year before diagnosis to 0.54+0.13 per patient per year (p=0.01). The changes in the PAT group (1.25+0.28 per patient per year one year before diagnosis to 0.53+0.14 per patient per year (p=0.034) were significant while in the PNAT group they were not.Conclusions:Adherence to treatment in patients with OSAS results in a significant reduction in physician claims and hospital stays.

Kapur, Vishesh; Blough, David K.; Sandblom, Robert E.; Hert, Richard; de Maine, James B.; Sullivan, Sean D.; Psaty, Bruce M.

doi: 10.1093/sleep/22.6.749pmid: 10505820

SummaryObstructive sleep apnea is an under-diagnosed, but common disorder with serious adverse consequences. Cost data from the year prior to the diagnosis of sleep-disordered breathing in a consecutive series of 238 cases were used to estimate the potential medical cost of undiagnosed sleep apnea and to determine the relationship between the severity of sleep-disordered breathing and the magnitude of medical costs. Among cases, mean annual medical cost prior to diagnosis was $2720 versus $1384 for age and gender matched controls (p<0.01). Regression analysis showed that the reciprocal of the apnea hypopnea index among cases was significantly related to log-transformed annual medical costs after adjusting for age, gender, and body mass index (p<0.05). We conclude that patients with undiagnosed sleep apnea had considerably higher medical costs than age and sex matched individuals and that the severity of sleep-disordered breathing was associated with the magnitude of medical costs. Using available data on the prevalence of undiagnosed moderate to severe sleep apnea in middle-aged adults, we estimate that untreated sleep apnea may cause $3.4 billion in additional medical costs in the U.S. Whether medical cost savings occur with treatment of sleep apnea remains to be determined.

Beusterien, Kathleen M.; Rogers, Ann E.; Walsleben, Joyce A.; Emsellem, Helene A.; Reblando, Joseph A.; Wang, Lixia; Goswami, Meeta; Steinwald, Bruce

doi: 10.1093/sleep/22.6.757pmid: 10505821

AbstractObjective:To evaluate the burden of illness of narcolepsy and assess the health-related quality-of-life (HQL) effects of oral modafinil, a wake-promoting therapy for excessive daytime sleepiness associated with narcolepsy.Methods:Subjects with narcolepsy enrolled in a nine-week, placebo-controlled, double-blind study and were randomized to placebo, modafinil 200 mg, or modafinil 400 mg. After the study, consenting subjects received modafinil in a 40-week open-label extension. A self-administered HQL questionnaire consisting of the 36-Item Short Form Health Survey (SF-36) and supplemental narcolepsy-specific scales was given to subjects at baseline, study endpoint, and several open-label timepoints.Results:481 subjects completed a baseline and double-blind endpoint HQL assessment. Compared to population norms, baseline HQL scores reflected substantial burden in vitality, social functioning, and performing usual activities. At study endpoint, subjects in the 400 mg modafinil group had significantly higher scores than placebo for 10 of the 17 HQL scales. The 400 mg modafinil group had more energy, fewer difficulties performing usual activities, fewer interferences with social activities, improved psychological well-being and higher productivity, attention and self-esteem compared to placebo subjects (p<.05). The positive treatment effects were sustained over the open-label extension.Conclusion:Modafinil significantly improves health-related quality of life in narcolepsy.

Okamoto-Mizuno, Kazue; Mizuno, Koh; Michie, Saeko; Maeda, Akiko; lizuka, Sachiko

doi: 10.1093/sleep/22.6.767pmid: N/A

SummaryThe objective of this study was to confirm the effect of humid heat exposure on sleep stages and body temperature. Seven healthy male volunteers with a mean age of 22.7±1.63, served as the subjects. The experiments were carried out under four different conditions of room temperature and relative humidity: 29°C RH 50% (29/50), 29°C RH 75% (29/75), 35°C RH 50% (35/50), and 35°C RH 75% (35/75). The subjects wearing only shorts slept from 23:00 to 7:00 on a bed, which was covered with a 100% cotton sheet. EEG, EOG, and mental EMG were recorded through the night. Rectal temperature (Tr) and skin temperature were measured continuously. The 35/75 condition caused more wake and a lower sleep efficiency index (SEI) and stage S3+S4 than 29/50 and 29/75. Stage REM and stage 3 were significantly decreased at 35/75 than at 29/50 and 35/50. Tr was maintained at a higher level at 35/75 than under the other conditions. Mean skin temperature was higher at 35/50 and 35/75 than at 29/50 and 29/75. These results suggest that humid heat exposure during night sleep increases the thermal load to supress the sleep-evoked Tr decrease, stage 3, SWS, and REM, and increase wakefulness.

Aikens, James E.; Vanable, Peter A.; Tadimeti, Lakshminarayana; Caruana-Montaldo, Brendan; Mendelson, Wallace B.

doi: 10.1093/sleep/22.6.775pmid: 10505823

AbstractStudy Objective:To determine patterns and relative intensity of psychopathology, as measured by the Minnesota Multiphasic Personality Inventory (MMPI), in 108 patients with either psychophysiological insomnia (PI; n=20), insomnia with psychiatric disorder (IPD; n=30), periodic limb movement disorder (PLM; n=28), or obstructive sleep apnea (OSA; n=30).Design:Cross-sectional.Setting:University sleep disorders center.Measurements and Results:Subjects completed the MMPI prior to overnight diagnostic polysomnographic assessment followed by Multiple Sleep Latency Test (MSLT). Seventy five percent of the entire sample had at least one MMPI elevation (T>70). Groups showed significant baseline differences in age, BMI, and MSLT latency (all ps<.05). Logistic regression indicated that even after statistically controlling for these three diagnostic covariates, MMPI elevation was more likely among PLM and IPD patients than OSA or PI patients (all ps<.05). Followup pairwise comparisons indicated that this same pattern of group differences occurred for the Depression, Psychasthenia, and Schizophrenia scales (all ps<.05).Conclusions:Irrespective of age, obesity, and daytime sleepiness, patients with untreated PLM or IPD are more likely to experience clinically significant psychological difficulties than those with either OSA or PI. These differences are most likely to be manifested in terms of depressive symptoms, anxiety symptoms (tension, worry, guilt), social alienation, and diminished mental concentration. Finally, PLM may be associated with greater MMPI elevations than previously suspected, and agree with earlier clinical reports of high rates of psychiatric treatment in PLM.

Sippel, Jeffrey M.; Giraud, George D.; Holden, William E.

doi: 10.1093/sleep/22.6.786pmid: 10505824

SummaryIn preliminary studies, human subjects complained of drowsiness after aerosolization of NG-nitro-L-arginine methyl ester (L-NAME) into the nasal passages. We compared the effects of a nasal aerosol of L-NAME (0.5 M, 4 ml) to those of saline on sleep onset latency and exhaled nasal nitric oxide (NO). L-NAME decreased sleep onset latency and exhaled nasal NO. Vasoconstriction and local effects of L-NAME on NO synthesis are unlikely to explain this effect since oxymetazoline, a vasoconstrictor, decreased exhaled NO but had no effect on sleep onset latency. We conclude that aerosolization of L-NAME to the nasal passages induces daytime sleepiness.

George, CFP; Smiley, A

doi: 10.1093/sleep/22.6.790pmid: N/A

AbstractBackground:As a group, patients with obstructive sleep apnea (OSA) are at increased risk of having automobile accidents. Previous studies using actual accident data have used only small numbers of subjects.Objective:To determine the rate of automobile accidents in a large population of OSA patients using objective data from the Ministry of Transportation of Ontario (MTO).Design:Retrospective studySetting:Academic sleep disorders clinic and laboratory.Participants:All cases of OSA polygraphically confirmed between June 1990 and June 1994.Interventions:Cases of OSA were a priori divided into groups based on apnea-hypopnea index (AHI): (OSA1- AHI 10–25, OSA2 - AHI 26–40, OSA3 - AHI>40) and driving records were obtained from the MTO. Age and sex matched controls were selected at random from drivers in the MTO driver database who hold passenger vehicle licences. Analysis was restricted to drivers with the same licence class.Main Outcome Measures:Primary outcome measure was accidents in the five years preceding diagnosis. Secondary outcome was citations during the same period.Results:There were 155 of 460 OSA patients with one or more accidents compared with 150 of 581 Controls for the same time period (x2=7.7,p<0.01).The rate of accidents/year, for the preceding five years, was 0.07±0.14 for Controls versus 0.09±0.14 for OSA (p <0.05). This difference could all be accounted for by increased accident rate in OSA patients with the highest AHI (OSA3) (MVA/yr: 0.11+0.15, 0.08+0.12, 0.06±0.14 for OSA groups 3,2,1 respectively) as there was no differences among Control, OSA1 and OSA2 accident rates. OSA patients had twice as many citations as Controls (1.74+2.13 vs 0.86+1.43 pO.001) although the types of citation were the same.Conclusions:Increased automobile accidents in OSA may be restricted to cases with more severe apnea (AHI >40). Despite the large sample size (an order of magnitude greater than previous reports using accident data) further study is needed with even larger numbers, including more measures of disease severity and rigorously controlling for driving exposure.