SLEEP

Littner, Michael

doi: 10.1093/sleep/22.7.833pmid: 10566901

Baghdoyan, H. A.; Lydic, R.

doi: 10.1093/sleep/22.7.835pmid: 10566902

AbstractRapid eye movement (REM) sleep is generated, in part, by activating muscarinic cholinergic receptors (mAChRs) in the medial pontine reticular formation (mPRF). Molecular cloning has identified five mAChR subtypes, and this study tested the hypothesis that the M2 subtype in the mPRF modulates the amount of REM sleep. This hypothesis cannot be tested directly, due to lack of subtype selective muscarinic agonists. However, the amount of REM sleep can be enhanced by mPRF microinjection of a muscarinic agonist, and the relative potencies of muscarinic antagonists to block the REM sleep enhancement can be determined. Two muscarinic antagonists, methoctramine and 4-DAMP, were studied. Six concentrations of each antagonist were microinjected into the mPRF of conscious cat 15 min prior to the agonist bethanechol. Nonlinear regression analysis was used to calculate the dose of antagonist that caused a 50% inhibition (ID50) of bethanechol-induced REM sleep. Bethanechol significantly increased (442%) the amount of time spent in REM sleep. Both methoctramine and 4-DAMP significantly blocked the bethanechol-induced REM sleep increase, with an ID50 of 1.8 µM and 0.6 µM, respectively. The ID50 ratio for methoctramine-to-4-DAMP (3.0) was similar to the affinity ratio of methoctramine-to-4-DAMP only at the M2 subtype (3.5), suggesting that the M2 subtype in the mPRF modulates the amount of REM sleep. This study also tested the null hypothesis that sleep-dependent respiratory depression evoked by mPRF cholinomimetics would not be antagonized by pretreatment of the mPRF with muscarinic antagonists. Neither methoctramine nor 4-DAMP antagonized the bethanechol-induced decrease in respiratory rate.

Akashiba, Tsuneto; Minemura, Hiroshi; Yamamoto, Hitoshi; Kosaka, Naoko; Saito, Osamu; Horie, Takashi

doi: 10.1093/sleep/22.7.849pmid: 10566903

AbstractTo evaluate the circadian pattern of blood pressure (BP) and the effects of nasal continuous positive airway pressure (CPAP) on patients with obstructive sleep apnea (OSA), we examined 24-hour BP in 38 male OSA patients with and without nasal CPAP. We measured the BP at 30-min intervals during daytime (800 to 2200) and nighttime (2200 to 800) hours. A “dipper” was defined as a patient who showed an average reduction of at least 10 mm Hg systolic and 5 mm Hg diastolic between daytime and nighttime values. The subjects were predominantly “non-dipper” (22 of 38 patients, 58%). Daytime hypertension (>160/95 mm Hg) was present in 11 of 38 patients (4 “dippers” and 7 “non-dippers”). After nasal CPAP treatment for 3 days, the average BP decreased significantly during the day and night in all subjects (p<0.05). Fifteen of 22 subjects who were “non-dippers” before treatment reversed to become “dippers.” And daytime hypertension was detected in only 5 of these patients during nasal CPAP treatment (4 “dippers” and 1 “non-dipper”). These results showed that the “non-dipper” status was common in patients with OSA, and that nasal CPAP restored the normal circadian “dipper” pattern. We suggest that nasal CPAP may contribute to an improved prognosis in patients with OSA because of a reduction in cardiovascular risk factors in “non-dipper” with severe OSA.

Ferini-Strambi, Luigi; Zucconi, Marco; Castronovo, Vincenza; Garancini, Paola; Oldani, Alessandro; Smirne, Salvatore

doi: 10.1093/sleep/22.7.859pmid: N/A

SummaryThe aim of this cross-sectional study was to evaluate the prevalence of sleep-disordered breathing by means of a validated portable instrument (MESAM IV) and to investigate the relationship between snoring and sleep apnea in a sample of Italian middle-aged female population. We randomly chose 750 subjects aged 40 to 65 years and 365 agreed to participate to the study. In this group, 19.7% of subjects were every-night snorers according to the questionnaire; when recorded, 54.2% snored for more than 10% of the night, and 7.1% for more than 50% of the night. Sleep apnea was also common: 10.7% of subjects had a respiratory disturbances per hour (RDI) between 5 and 9, 7.7% an RDI between 10 and 19, and 2.2% had an RDI ≥20. Snoring percentage and RDI were significantly correlated. However, 50% of subjects who snored for more than half the night had no evidence of sleep apnea. Snoring amount >50% resulted influenced by body mass index, while RDI>10 was influenced by neck diameter. We concluded that in middle-aged women, both snoring and sleep apnea are very common. A high percentage of snoring is not essential for the occurrence of sleep apnea, nor it necessarily indicates the presence of sleep apnea.

Luboshitzky, Rafael; Lavi, Shachar; Lavie, Peretz

doi: 10.1093/sleep/22.7.867pmid: 10566905

AbstractThe role of melatonin in normal sleep-wake regulation has been inferred from the temporal relationships between its cycle and the 24h cycle in sleep propensity. Pharmacological doses of melatonin were reported to have sleep-inducing effects in insomniacs. The current study investigated the relationship between melatonin and sleep stages in groups of hypogonadal men with abnormal melatonin levels. We were also interested in examining what would happen to these relationships during testosterone replacement therapy. Male patients with hypogonadotropic hypogonadism (IGD, n=6), constitutional delayed puberty (DP, n=6), and Klinefelter's syndrome (KS, n=5) before and during testosterone replacement therapy were studied. Six patients with KS and normal testosterone levels were also studied. Results were compared with those obtained in normal controls (n=6). Serum samples were obtained at 15 min intervals from 1900–0700h in a controlled light-dark environment with simultaneous polysomnographic sleep recordings. Serum melatonin levels were the highest in IGD and DP and lowest in KS patients. A lower percentage of sleep stage 2 and higher percentage of stage 3/4 were observed in IGD and DP groups while KS patients had higher percentage of stage 2 and lower percentage of stage 3/4 as compared to controls. Slow wave sleep was the highest in IGD and the lowest in KS groups. Serum melatonin levels were lowest in KS groups. Serum melatonin levels were lowest in sleep stage 3/4, higher in stage 2 and highest in REM sleep when all groups were combined and averaged together. However, in the IGD group, melatonin levels were actually lowest in REM sleep. Also in the KS group, melatonin levels were lower in REM than during sleep stage 2. Serum melatonin levels were lowest in sleep stage 3/4 in all groups, higher in stage 2, and highest in REM sleep. During waking periods, melatonin levels were the highest in untreated IGD, DP and KS patients. Testosterone treatment given to these patients, although normalized, their melatonin levels did not statistically significantly change these correlations. These data demonstrate that relative melatonin concentrations are associated with sleep stages in hypogonadal and normal men. The results also indicate that the association between melatonin and the reproductive hormones are independent of the synchronizing effects of melatonin on sleep homeostasis.

Benhaberou-Brun, Dalila; Lambert, Chantal; Dumont, Marie

doi: 10.1093/sleep/22.7.877pmid: 10566906

AbstractStudy objectives:To test the hypothesis that nightworkers’ diurnal sleep complaints are associated with the timing of melatonin secretion.Design:After a minimum of three consecutive night shifts, the subjects were admitted to the laboratory for 24 hours during which they were allowed to eat and sleep ad lib. Urine was collected every two hours under dim illumination (<25 lux). Concentration of urinary 6-sulphatoxymelatonin (UaMT6s) was determined by radioimmunoassay. Sleep quality was assessed by questionnaires.Setting:NAParticipants:Two groups of 15 night nurses with mild and severe daytime sleep complaints.Interventions:NAResults:The proportion of the episode of UaMT6s excretion happening during the day (between 08:00 and 00:00 hours) was smaller in the group of nightworkers with severe daytime sleep complaints, and was negatively correlated with the severity of the complaints over the 30 subjects. A longer duration of melatonin secretion was associated with a lower severity of daytime sleep complaints. However, in most of the subjects with good daytime sleep quality, melatonin secretion remained essentially nocturnal, and the overlap with the time of their sleep episode was small or even absent.Conclusions:Timing and duration of melatonin secretion were associated with better daytime sleep quality when the subjects had an increased proportion of melatonin secreted during the day. When there was an indication of circadian phase shift, the direction of the shift was not of primary importance for daytime sleep quality. A longer duration of melatonin secretion may increase the tolerance to an abnormal circadian phase.

Dorsey, Cynthia M.; Teicher, Martin H.; Cohen-Zion, Mairav; Stefanovic, Louis; Satlin, Andrew; Tartarini, Wendy; Harper, David; Lukas, Scott E.

doi: 10.1093/sleep/22.7.891pmid: 10566907

AbstractThe purpose of this study was to investigate the relationship between core body temperature and sleep in older female insomniacs and changes in that relationship as a result of passive body heating (PBH). An increase in body temperature early in the evening by way of PBH in older female insomniacs increased SWS in the early part of the sleep period and improved sleep continuity. Fourteen older female insomniacs (60–73 years old) participated in at least two consecutive nights of PBH involving hot (40–40.5°C) baths 1.5 – 2 hours before bedtime. Hot baths resulted in a significant delay in the phase of the core body temperature rhythm compared to baseline nights. This delay in temperature phase paralleled the improvements in sleep quality.

Hening, WA; Walters, AS; Wagner, Mary; PharmD, ; Rosen, Raymond; Chen, Vincent; Kim, Steven; Shah, Mona; Thai, Oanh

doi: 10.1093/sleep/22.7.901pmid: 10566908

AbstractStudy Objectives:To determine if motor restlessness in the Restless Legs Syndrome (RLS) shows a circadian rhythm with maximum at night, as previously found for subjective discomfort and periodic limb movements (PLMs), and to correlate RLS peak intensity with the core temperature cycle.Design:Subjects underwent two days of normally timed wakefulness and sleep followed by a night and subsequent day of sleep deprivation. Activity was standardized through modified suggested immobilization tests (mSITs).Setting:The study was conducted in a laboratory environment with a bedroom equipped for polysomnography during sleep and the mSITs.Patients:Nine patients (mean age 59.8 +/− 11.3 years {range: 33 − 72}; 4 males, 5 females) with clinically severe idiopathic RLS. Interventions: Patients were monitored with continuous ambulatory activity and core temperature recording. The mSITs were performed every three hours while subjects were awake. During the mSITs, subjective discomfort was measured every 15 minutes while motor restlessness was assessed through activity monitoring.Measurements and Results:Subjective discomfort and motor restlessness increased from a trough in the morning to a maximum at night in the hours following midnight. Peak intensity was found on the falling phase of the core temperature cycle, whose circa-dian rhythm appeared to be within the normal range for age.Conclusions:An independent circadian factor modulates the intensity of RLS, which seems to peak on the falling phase of the core temperature cycle. Therefore, the diagnostic criteria that RLS occurs with rest and during the night have independent bases. Furthermore, RLS may be partially controlled by some process or substance whose level varies with the normal circadian rhythm.

Loredo, José S.; Clausen, Jack L.; Ancoli-Israel, Sonia; Dimsdale, Joel E.

doi: 10.1093/sleep/22.7.916pmid: 10566909

AbstractStudy Objectives:Measurement of arousals from sleep is clinically important, however, their definition is not well standardized, and little data exist on reliability. The purpose of this study is to determine factors that affect arousal scoring reliability and night-to-night arousal variability.Design:The night-to-night arousal variability and interscorer reliability was assessed in 20 subjects with and without obstructive sleep apnea undergoing attended polysomnography during two consecutive nights. Five definitions of arousal were studied, assessing duration of electroencephalographic (EEG) frequency changes, increases in electromyographic (EMG) activity and leg movement, association with respiratory events, as well as the American Sleep Disorders Association (ASDA) definition of arousals.Setting:NAPatients:NAInterventions:NAResults:Interscorer reliability varied with the definition of arousal and ranged from an Intraclass correlation (ICC) of 0.19 to 0.92. Arousals that included increases in EMG activity or leg movement had the greatest reliability, especially when associated with respiratory events (ICC 0.76 to 0.92). The ASDA arousal definition had high interscorer reliability (ICC 0.84). Reliability was lowest for arousals consisting of EEG changes lasting <3 seconds (ICC 0.19 to 0.37). The within subjects night-to-night arousal variability was low for all arousal definitionsConclusion:In a heterogeneous population, interscorer arousal reliability is enhanced by increases in EMG activity, leg movements, and respiratory events and decreased by short duration EEG arousals. The arousal index night-to-night variability was low for all definitions.

Ohayon, Maurice M.; Guilleminault, Christian; Zulley, Jurgen; Palombini, Luciana; Raab, Hubert

doi: 10.1093/sleep/22.7.925pmid: 10566910

AbstractObjectives:To validate the Sleep-EVAL expert system, a computerized tool designed for the assessment of sleep disorders, against polysomnographic data and clinical assessments by sleep specialists.Design:Patients were interviewed twice, once by a physician using Sleep-EVAL and again by a sleep specialist. Polysomnographic data were also recorded to ascertain diagnoses. Agreement between diagnoses generated by Sleep-EVAL and those formulated by sleep specialists was determined via the kappa statistic.Settings:Sleep disorder centers at Stanford University (USA) and Regensburg University (Germany).Patients:105 patients aged 18 years or over.Interventions:NAResults:Sleep-EVAL made an average of 1.32 diagnoses per patient, compared with 0.93 for the sleep specialists. Overall agreement on any sleep-breathing disorder was 96.9% (Kappa .94). More than half of the patients were diagnosed with obstructive sleep apnea syndrome (OSAS); the agreement rate for this specific diagnosis was 96.7% (Kappa .93).Conclusions:The findings indicate that the Sleep-EVAL system is a valid instrument for the recognition of major sleep disorders, particularly insomnia and OSAS.