The paradox of sleep: the early years.
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Animals↗
Biomedical subjects
W C Dement
Publications and source records attributed to W C Dement.
Cervical positioning for reduction of sleep-disordered breathing in mild-to-moderate OSAS.
The objective of this study was to assess whether cervical positioning could improve mild to moderate cases of the obstructive sleep apnea syndrome (OSAS). Eighteen subjects recruited from a tertiary sleep disorders clinic population with mild to moderate cases of OSAS were evaluated using a custom-fitted cervical pillow designed to increase upper airway caliber by promoting head extension. The subjects used their usual pillows during two consecutive recorded baseline nights in our laboratory. They then used the cervical pillow for 5 days at home and returned for 2 consecutive recorded nights at our laboratory to use the cervical pillow. During the nights in our laboratory, the subjects completed questionnaires, were videotaped to record head and body position, and had full polysomnography. The subjects had a significant trend toward improvement in their respiratory disturbance indices with use of the cervical pillow, despite spending more time in the supine position and having similar amounts of REM sleep in the baseline and experimental conditions. They also had nonsignificant trends toward improvements in their sleep efficiency and subjective depth of their sleep as well as significantly fewer arousals and awakenings in the experimental compared with the baseline condition. We propose that cervical positioning (i.e., head extension) with a custom-fitted cervical pillow provides a simple, noninvasive, and comfortable means of reducing sleep-disordered breathing in patients with mild to moderate OSAS.
Adolescent↗
Comparison of actigraphic, polysomnographic, and subjective assessment of sleep parameters in sleep-disordered patients.
OBJECTIVE: Comparison of polysomnography (PSG)-derived sleep parameters (total sleep time, sleep efficiency, and number of awakenings) to those derived from actigraphy and subjective questionnaires. BACKGROUND: Actigraphy is commonly used to assist sleep specialists in the diagnosis of various sleep and circadian-rhythm disorders. However, few validation studies incorporate large sample sizes, typical sleep clinic patients, or comparisons with subjective reports of sleep parameters. METHODS: Clinical series with 100 consecutive sleep-disordered patients (69 men, 31 women, mean age of 49+/-14.7 years) at a tertiary sleep disorders center. Sensitivity, specificity, and accuracy measures were obtained from epoch-by-epoch comparison of PSG and actigraphic data. Subjective sleep parameter data were derived from questionnaires given to subjects in the morning following their recording night. RESULTS: We found that total sleep time and sleep efficiency did not significantly differ between PSG data and the combined data obtained from actigraphy and subjective reports. Using a high-threshold (low-wake-sensitivity) actigraphic algorithm, the number of awakenings was not significantly different from those detected by PSG. CONCLUSIONS: We recommend the use of subjective data as an adjunct to actigraphic data in estimating total sleep time and sleep efficiency in sleep-disordered patients, especially those with disorders of excessive somnolence.
Journal Article↗
Remembering Nathaniel Kleitman.
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History, 20th Century↗
Snoring and sleep quality: everyone deserves a good night's rest.
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Humans↗
Cervical positional effects on snoring and apneas.
We examined the effects of cervical position on the Obstructive Sleep Apnea Syndrome (OSAS) through the use of a custom-designed cervical pillow which promoted neck extension. Twelve subjects with OSAS were recruited from a tertiary sleep disorder clinic population. Of the twelve subjects, three had mild cases of OSAS, four had moderate cases, and the remaining five had severe cases. The subjects used their usual pillows during two consecutive recorded baseline nights in our laboratory. The subjects then used the cervical pillow for five days at home, and returned for two consecutive recorded nights at our laboratory while using the cervical pillow. During the nights in our laboratory, the subjects completed questionnaires, were videotaped to record head and body position, and had their breathing parameters recorded during sleep. Subjects with mild OSAS cases had a non-significant improvement in the severity of their snoring and a significant improvement in their respiratory disturbance index with the cervical pillow, while subjects with moderate OSAS cases showed no improvement in these parameters. Subjects with severe OSAS cases showed slight improvement in some measures of their abnormal respiratory events during the experimental period.
Adult↗
Breeding history of the Stanford colony of narcoleptic dogs.
Narcolepsy is a disabling sleep disorder of unknown aetiology. In humans, the disease is mostly sporadic, with a few familial cases having been reported. In 1973 a sporadic case of narcolepsy was reported in a poodle, and in 1975 familial cases of narcolepsy occurred in dobermanns. As with human narcoleptics, these narcoleptic dogs exhibited excessive daytime sleepiness and cataplexy. A colony of narcoleptic dogs was established at Stanford University in 1976 to study the pathophysiology of the disease. Between 1976 and 1995, a total of 669 animals of various breeds were born, of which 487 survived. Dobermanns accounted for 78 per cent of the total. The narcolepsy genotype in dobermanns had no significant influence on puppy mortality rate (numbers of stillborn and survival rate). The sex, maternal parity or the age of the sire or dam had no significant effect. The percentage of stillborn puppies increased from 6.1 per cent in outbred litters to 15.4 per cent in inbred litters (P = 0.10). Birth season also had a significant effect, and the highest survival rate (P = 0.02), and the lowest percentage of stillborn puppies (P = 0.09) occurred between April and June.
Animals↗
Neuropharmacological characterization of basal forebrain cholinergic stimulated cataplexy in narcoleptic canines.
Basal forebrain (BF) cholinergic regulation of cataplexy was investigated in narcoleptic canines. Specific cholinergic agonists and antagonists, and excitatory or inhibitory amino acid neurotransmitter receptor agonists, were perfused through microdialysis probes implanted bilaterally in the BF of narcoleptic canines. Cataplexy was monitored using the food-elicited cataplexy test (FECT) and recordings of electroencephalogram, electrooculogram, and electromyogram. In narcoleptic canines, carbachol and oxotremorine (10(-5)-10(-3) M), but not McN-A-343 or nicotine (10(-4)-10(-3) M), produced a dose-dependent increase in cataplexy. In addition, N-methyl-d-aspartate (10(-4)-10(-3) M) and kainic acid (10(-5)-10(-4) M) did not have any effects, while muscimol (10(-3) M) produced a weak (P < 0.10) increase in cataplexy. In control canines, carbachol (10(-5)-10(-3) M), but not oxotremorine (10(-4)-10(-3) M), produced muscle atonia after the highest concentration in one of three animals. Carbachol (10(-3) M)-induced cataplexy in narcoleptic canines was blocked by equimolar perfusion with the muscarinic antagonists atropine, gallamine, and 4-DAMP but not pirenzepine. These findings indicate that carbachol-stimulated cataplexy in the BF of narcoleptic canines is mediated by M2, and perhaps M3, muscarinic receptors. The release of acetylcholine in the BF was also examined during FECT and non-FECT behavioral stimulation in narcoleptic and control canines. A significant increase in acetylcholine release was found in both narcoleptic and control BF during FECT stimulation. In contrast, simple motor activity and feeding, approximating that which occurs during an FECT, did not affect acetylcholine release in the BF of narcoleptic canines. These findings indicate that BF acetylcholine release is enhanced during learned emotion/reward associated behaviors in canines.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
Development of cataplexy in genetically narcoleptic Dobermans.
Forty-two genetically narcoleptic Doberman puppies [20 pure narcoleptic (N) puppies (from four narcoleptic x narcoleptic crosses) and 22 backcross narcoleptic (BN) puppies (from six narcoleptic x heterozygous crosses)] were systematically observed during the developmental period (4-24 weeks) to assess the age at onset and severity of cataplexy, a pathological manifestation of REM sleep atonia seen in narcolepsy. The mean age of onset of cataplexy was 9.69 +/- 1.15 weeks, with a median age of 7 weeks. The severity of cataplexy increased with age and reached a plateau at around 16-24 weeks. The effects of cross type (N vs BN) and sex on the development of cataplexy were analyzed. There was no difference in severity between N and BN puppies (P = 0.51). However, females had more severe cataplexy than males (P = 0.01), and this trend was preserved in five of the six litters that had both male and female puppies. These results suggest that the pathophysiological process in genetic canine narcolepsy emerges during the early developmental period and that it may involve a differential development in males and females. Furthermore, our results revealed that cataplexy onset corresponds to the emergence of adult-like REM sleep and to previously reported neuroanatomical and neurochemical abnormalities in canine narcolepsy.
Age of Onset↗
Effects of adrenalectomy and subsequent corticosterone replacement on rat sleep state and EEG power spectra.
Individual effects of corticotropin-releasing hormone (CRH) and glucocorticoids on sleep have been difficult to discern due to the feedback effects each hormone exerts on the other. In addition, it is not known whether hypothalamic-pituitary-adrenal axis hormones alter sleep homeostasis or circadian influences on sleep propensity. We therefore analyzed sleep architecture and electroencephalographic (EEG) power in freely moving rats before and after removal of corticosterone (thus elevating endogenous CRH) by surgical adrenalectomy. Adrenalectomy reduced the amplitude of the diurnal rhythms of maximal and average sleep bout lengths (P < 0.004). After adrenalectomy, power from 1 to 4 Hz decreased (P < 0.042), whereas power from 9 to 12 Hz increased in the power spectra of the EEG recording (P = 0.001). Administration of physiological corticosterone replacement reversed some of these effects. Supraphysiological corticosterone replacement in adrenalectomized rats reduced the amount of non-rapid-eye-movement sleep in the 24-h cycle (P = 0.001). During each endocrine condition, rats were sleep deprived for 6 h. Endocrine status did not alter the subsequent homeostatic response to sleep deprivation. Thus ADX and supraphysiological corticosteroid replacement each altered sleep architecture without a demonstrable effect on sleep homeostasis.
Adrenalectomy↗
Normative data on snoring: a comparison between younger and older adults.
Snoring is a common sleep-related behaviour. Increased body mass index (BMI), cranio-facial anatomical features, and older age have been linked to the occurrence of snoring. While mostly middle-aged populations have been studied for the occurrence of snoring and sleep-related breathing abnormality, this study was designed to assess the subjective report of snoring and the objective measurement of snoring at the two extremes of human age. The study design called for measurement of snoring in two age groups (college students; n=155 and older subjects; mean age 64.1 yrs n=134) with a mean age difference of 45 yrs. Snoring was assessed with a validated recording device. A validated questionnaire was used to subjectively assess snoring and obtain relevant sleep-related information. Students and older subjects differed in the self-report of snoring. While 83% of students reported "never" or "rarely" snoring only 35% of older subjects fell into these categories. Measurement of snoring during sleep revealed that students spent more time during sleep with continuous snoring than older subjects. In older subjects, a reduction in continuous snoring was accompanied by an increase in apnoeic snoring. Subjective snoring frequency correlated with continuous snoring in students only. A positive family history of snoring increased the odds ratio for self-reported snoring but not for recorded snoring. It has been shown that snoring frequency can vary depending on age and that the congruency between perceived snoring frequency and recorded snoring is influenced by the age of an individual.
Adult↗
The study of human sleep: a historical perspective.
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History, 20th Century↗
Serotonin-containing fibers in the suprachiasmatic hypothalamus attenuate light-induced phase delays in mice.
Photic and non-photic stimuli phase shift and entrain circadian rhythms through distinct but interacting mechanisms which impinge on the suprachiasmatic nucleus (SCN), the circadian pacemaker. Our understanding of this mechanism is incomplete. Serotonin (5-HT) injected locally at the SCN reduces light-induced glutamate release and decreases the expression of c-fos, a marker of photic transduction. Furthermore, in SCN slices, 5-HT application reduces field potentials after optic nerve stimulation. We therefore predicted that 5-HT-terminal destruction restricted to the SCN would augment phase shifts of circadian rhythms induced by light exposure. To investigate this possibility, we compared photic phase delays and Fos-like immunoreactivity in mice which had previously received bilateral infusions directed at the SCN containing either the selective 5-HT neurotoxin 5,7-dihydroxytryptamine (DHT, n = 16) or vehicle (VEH, n = 12). Phase delays after a light pulse given during the mid-subjective night (30 lux, 30 min starting at circadian time (CT) 12-20) in DHT-mice were 50% greater than in VEH-mice (P = 0.017). DHT mice (n = 5) had 76% larger Fos responses to a mid-subjective night light pulse than VEH-mice (n = 5) (P = 0.029). We conclude that 5-HT at or near the SCN in mice reduces photic phase shifts and modulates the magnitude of the photic phase response in the mouse.
5,7-Dihydroxytryptamine↗
Effects of thyrotropin-releasing hormone and its analogs on daytime sleepiness and cataplexy in canine narcolepsy.
The therapeutic potential of thyrotropin-releasing hormone (TRH) and TRH analogs in narcolepsy, a sleep disorder characterized by abnormal rapid eye movement (REM) sleep and daytime sleepiness, was examined using the canine model. The effects of TRH and the biologically stable TRH analogs CG3703, CG3509, and TA0910 on daytime sleep and cataplexy, a symptom of abnormal REM sleep, were assessed using polysomnographic recordings and the food elicited cataplexy test (FECT), respectively. CG3703 (100 and 400 microg/kg, i.v.) and TA0910 (100 and 400 microg/kg, i.v.) significantly increased wakefulness and decreased sleep in narcoleptic canines, whereas TRH (400 and 1600 microg/kg, i.v.) had no significant effect. TRH (25-1600 microg/kg, i.v.) and all three TRH analogs, CG3703 (6. 25-400 microg/kg, i.v., and 0.25-16 mg/kg, p.o.), CG3509 (25-1600 microg/kg, i.v.), and TA0910 (25-1600 microg/kg, i.v.), significantly reduced cataplexy in canine narcolepsy. These compounds did not produce any significant side effects during behavioral assays, nor did they alter free T3 and T4 levels in serum even when used at doses that completely suppressed cataplexy. Although more work is needed to establish the mode of action of TRH analogs on alertness and REM sleep-related symptoms, our results suggest a possible therapeutic application for TRH analogs in human sleep disorders.
Animals↗
Mesopontine organization of cholinergic and catecholaminergic cell groups in the normal and narcoleptic dog.
Canine narcolepsy is a unique experimental model of a human sleep disorder characterized by excessive daytime sleepiness and cataplexy. There is a consensus recognition of an imbalance between cholinergic and catecholaminergic systems in narcolepsy although the underlying mechanisms remain poorly understood. Possible substrates could be an abnormal organization, numbers and/or ratio of cholinergic to catecholaminergic cells in the brain of narcoleptic dogs. Therefore, we sought to characterize the corresponding neuronal populations in normal and narcoleptic dogs (Doberman Pinscher) by using choline acetyltransferase (ChAT), nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase, tyrosine hydroxylase (TH), and dopamine beta-hydroxylase (DBH). Cholinergic cell groups were found in an area extending from the central to the gigantocellular tegmental field and the periventricular gray corresponding to the pedunculopontine tegmental nucleus (PPT), the laterodorsal tegmental nucleus (LDT), and the parabrachial nucleus. An almost perfect co-localization of ChAT and NADPH-diaphorase was also observed. Catecholaminergic cell groups detected included the ventral tegmental area, the substantia nigra, and the locus coeruleus nucleus (LC). The anatomical distribution of catecholaminergic neurons was unusual in the dog in two important aspects: i) TH- and/or DBH-immunoreactive neurons of the LC were found almost exclusively in the reticular formation and not within the periventricular gray, ii) very few, if any TH-positive neurons were found in the central gray and dorsal raphe. Quantitative analysis did not reveal any significant differences in the organization and the number of cells identified in the LDT, PPT, and LC of normal and narcoleptic dogs. Moreover, the cholinergic to catecholaminergic ratio was found identical in the two groups. In conclusion, the present results do not support the hypothesis that the neurochemical imbalance in narcolepsy could result from abnormal organization, numbers, or ratio of the corresponding neuronal populations.
Animals↗
Diagnosis and treatment of sleep apnea within the community. The Walla Walla Project.
BACKGROUND: Patients with sleep disorders are common in primary care, yet most physicians lack training in the diagnosis and treatment of such patients. OBJECTIVES: To enhance recognition of sleep disorders by community physicians and transfer the diagnostic testing and care of such patients from tertiary care centers to the local community. To present our polysomnogram experience relevant to sleep apnea. METHODS: Sleep disorders specialists provided a community with education, diagnostic equipment, and ongoing support as sleep disorders expertise was established locally. Outcomes for a 2-year period were assessed by chart review, patient questionnaire, tabulation of polysomnographic data, and comparison with published reports from specialized centers. RESULTS: Referral for sleep testing increased by almost 8-fold in patients at the Walla Walla Clinic in Walla Walla, Wash, from 0.27% (2 of 752 cases reviewed) to 2.1% (294 of 14330 internal medicine patients). Data were collected from all community physicians for a 2-year period on 360 new patients who underwent polysomnogram testing. This resulted in the diagnosis of sleep-related breathing disorders in 81% and periodic leg movements of sleep in 18%. Nasal continuous positive airway pressure treatment was given to 228 patients (average baseline apnea index of 19.1), representing a higher volume of patients than at many traditional sleep centers, yet compliance with continuous positive airway pressure was comparable. CONCLUSIONS: Sleep apnea is significantly underrecognized by primary care physicians. As a result of the intervention, local sleep expertise was established and large numbers of patients were discovered and treated in the community. Thus, a significant public health problem is identified and a solution established.
Diagnosis, Differential↗
The morbidity of insomnia uncomplicated by psychiatric disorders.
The morbidity of sleep problems has been well documented; however, they are frequently associated with and are symptomatic of several psychiatric disorders. It is unclear how much of the morbidity can be accounted for by the associated psychiatric and substance abuse disorders and medical problems, and how much by the sleep problems per se. Sleep problems may also be an early sign of a psychiatric problem. This paper reports data from an epidemiologic community survey of over 10,000 adults living in three U.S. communities. A structured diagnostic assessment of psychiatric disorders as well as assessment of the presence of insomnia not due to medical conditions, medication, drug or alcohol abuse, and a 1-year follow-up were completed. Persons with insomnia in the past year without any psychiatric disorders ever (uncomplicated insomnia); with a psychiatric disorder in the past year (complicated insomnia); and with neither insomnia nor psychiatric disorders ever were compared on treatment utilization and the first onset of a psychiatric disorder in the subsequent year. Eight percent of those with uncomplicated as compared with 14.9% with complicated insomnia and 2.5% with neither had sought treatment from the general medical sector for emotional problems in the 6 months prior to the interview. The rates of treatment sought from the psychiatric specialty sector were 3.8%, 9.4%, and 1.2%, respectively. These differences were significant after controlling for sociodemographic characteristics and were sustained when the persons were interviewed 1 year later. Uncomplicated insomnia was also associated with an increase in risk for first onset of major depression, panic disorder, and alcohol abuse over the following year. Insomnia, even in the absence of psychiatric disorders, is associated with increased use of general medical and mental health treatment for emotional problems and for the subsequent first onset in the following year of some psychiatric disorders. Early diagnosis and treatment of uncomplicated insomnia may be useful.
Adult↗