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Biomedical subjects

W C Dement

Publications and source records attributed to W C Dement.

At least 127 records · Page 7Linked to original sources
PubMed1988

Role of central alpha-1 adrenoceptors in canine narcolepsy.

The role of central alpha-1 adrenergic receptors in cataplexy was investigated in genetically narcoleptic Doberman pinschers. Treatment of narcoleptic dogs with 25-600 micrograms/kg prazosin, a selective alpha-1 adrenergic receptor blocker, exacerbated cataplexy, whereas treatment with the alpha-1 agonist, methoxamine, ameliorated it. Subsequent studies showed that the beneficial effects of classical treatments of human narcolepsy (amphetamines and tricyclic antidepressants) are antagonized by prazosin, suggesting that these drugs are active through an indirect alpha-1 stimulation (via an increase of norepinephrine in the synaptic cleft). Other studies confirmed that the observed effects were not due to peripheral alpha-1 cardiovascular involvement. Atropine, a central anticholinergic agent, but not methylatropine, a peripheral one, completely suppressed the prazosin effect, which suggests that adrenergic and cholinergic systems act sequentially and not independently to generate cataplexy. Little is known about the physiological role of central alpha-1 adrenoceptors. This series of experiments implicates these receptors in narcolepsy-cataplexy.

Animals↗
PubMed1988

Determinants of daytime sleepiness in obstructive sleep apnea.

To investigate determinants of daytime sleepiness in obstructive sleep apnea syndrome (OSAS), we studied 100 unselected OSAS patients by nocturnal polygraphic recording and the Multiple Sleep Latency Test (MSLT). Data obtained were submitted to three types of analysis. Respiratory disturbance index, oxygen saturation indices, body mass index, and total nocturnal sleep time did not significantly correlate with daytime sleepiness, as measured by the MSLT. Analysis of subgroups based on weight and degree of alertness also showed a nonsignificant correlation with daytime sleepiness. The best predictor of the excessive daytime sleepiness (EDS) frequently found in OSAS patients was the nocturnal polygraphic recording of the sleep disturbances and sleep structure anomalies that reflect the brain's overall dysfunction in OSAS. Understanding why an electroencephalogram arousal response occurs during sleep in association with abnormal breathing and how this response can become blunted may help us to better predict the development of EDS.

Body Weight↗
PubMed1988

Sleep apnea and mortality in an aged cohort.

In the aged, sleep may be a vulnerable period for death from cardiovascular causes. Because of its high prevalence in the elderly, sleep apnea has been suggested to be one mechanism contributing to such sleep-related mortality. In this study, a cohort of 198 non-institutionalized elderly individuals (mean age at entry = 66) were followed for periods up to 12 years after initial polysomnography. The mortality ratio for sleep apnea (defined as a Respiratory Disturbance Index of over 10 events per sleep hour) was estimated to be 2.7 (95% CI = .95, 7.47). Multiple regression with the Cox proportional hazards model suggested that cardiovascular death was most clearly associated with age in this cohort. These results raise the possibility that "natural" death during sleep in the elderly may be associated with specific pathophysiological events during sleep.

Aged↗
PubMed1988

Profile of mood states changes during and after 5 weeks of nightly triazolam administration.

This double-blind, placebo-controlled study investigated rebound anxiety during and after 5 weeks of nightly use of triazolam 0.5 mg, a short half-life, rapidly absorbed benzodiazepine hypnotic. The study subjects were chronic insomniacs with moderate levels of psychopathology and prior use of hypnotics. Anxiety was assessed with the Profile of Mood States (POMS), instead of the anxiety scales more typically used in psychopharmacology: the Hamilton Rating Scale for Anxiety and a visual analogue scale. The POMS test was administered twice a day during the study. The results indicated that triazolam was not associated with increased anxiety the morning or the evening after previous-night drug administration. The results are discussed in view of the methodological issues in assessing anxiety in prior studies.

Adult↗
PubMed1987

Brain dopamine receptor levels elevated in canine narcolepsy.

Concentrations of dopamine D2 receptors in discrete brain areas differed significantly between dogs with the genetically transmitted form of narcolepsy, and age- and breed-matched controls. D2 receptors were assayed and quantified with Scatchard analysis using [3H]spiperone. Receptor densities in the nucleus accumbens, rostral caudate, and amygdala were consistently higher in narcoleptic animals. In amygdala, dopamine receptor abnormalities were associated with elevated dopamine and 3,4-dihydroxyphenylacetic acid concentrations, but no change in 3-methoxytyramine or homovanillic acid concentrations. These data indicate mesolimbic system involvement in canine narcolepsy and point to impaired dopamine release as a possible etiologic factor.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

HLA-DR restriction-fragment-length polymorphisms in narcolepsy.

Seventeen white patients from the Stanford Sleep Disorders Clinic complaining of excessive daytime somnolence (EDS) were selected for restriction-fragment-length polymorphism (RFLP) studies. Fourteen of the patients with clinically diagnosed narcolepsy were seropositive for DR2. RFLP analysis of these patients compared with a homozygous DR2-Dw2 cell line failed to reveal any polymorphism when digested with six restriction endonucleases and hybridized with three different cDNA probes. None of the three patients with central nervous system hypersomnia, a syndrome similar to narcolepsy, were DR2-positive. We conclude that any polymorphism of the DR beta, DQ alpha, or DQ beta genes of DR2 narcoleptics that might distinguish them from DR2 normals cannot be resolved through RFLP analysis.

HLA-D Antigens↗
PubMed1987

Daytime sleepiness: quantification of a behavioral state.

A neurophysiological technique that quantifies drowsiness as the speed of falling asleep at intervals across a day is used to identify patterns of sleepiness/alertness. The Multiple Sleep Latency Test (MSLT) reveals a daily biphasic organization of sleepiness that is affected in predictable ways by the length and continuity of nocturnal sleep on one or several nights, and by maturation, aging, sleep pathology, and drug ingestion. The systematic nature of these relationships provides impetus to efforts examining the neurobiological mechanisms subserving the delicate balance of sleep and wakefulness.

Adolescent↗
PubMed1987

Risk factors for sleep disordered breathing in heterogeneous geriatric populations.

This cross-sectional, multivariate study investigated associations between sleep disordered breathing (SDB) and putative risk factors in a heterogeneous group of 720 individuals over the age of 50 years studied during all-night in-lab polysomnography. Results indicated that: aged men were more likely to show impaired respiration during sleep than aged women; excessive daytime somnolence and parasomniac symptoms (snoring, gasping during sleep) were associated with SDB but insomnia was not; obesity accounted for more variance in SDB than age per se, implying that the prevalence of SDB in some elderly persons could be related to the deposition of body fat seen as individuals grow older. All four risk factors (age, sex, obesity, and symptomatic status) were statistically significant and independent predictors of impaired respiration in sleep in the elderly.

Age Factors↗
PubMed1987

Cetirizine effects on objective measures of daytime sleepiness and performance.

Sixty healthy men and women with no sleep complaints, 21 to 45 years of age (mean age 28), were randomly assigned to one of five parallel groups that received one of the following: cetirizine 5 mg (n = 13), 10 mg (n = 13), or 20 mg (n = 11); hydroxyzine 25 mg (n = 12); or placebo (n = 11). After one adaptation night in the lab, the subjects' sleep patterns were recorded from 2300 to 0730 hours. Subjects were in bed during this period. When they awoke at 0730, a test agent was administered according to double-blind technique. Multiple Sleep Latency Tests (MSLT: 20-minute opportunities to fall asleep in bed while EEG and eye movements are recorded) were given at two-hour intervals throughout the day, and a 30-minute vigilance performance test was given at 1000 and 1600 hours. Subjects receiving cetirizine in doses of 5 to 20 mg did not differ from placebo controls in any objective or subjective measure of daytime alertness. Subjects receiving hydroxyzine were significantly more sedated and showed slower reaction times than the placebo control group for at least four hours after treatment. Self-rated feelings of sleepiness, impairment, and fatigue did not differ significantly between groups. This suggests that hydroxyzine subjects may not have been aware of their sleepiness and slower reaction times.

Adult↗
PubMed1987

Modulation of activity of the striatal dopaminergic system during the hibernation cycle.

To evaluate how the activity of a well-established neurotransmitter pathway is modulated by a behavioral state, 3H-spiperone binding sites and dopamine (DA) and DA metabolite concentrations were measured in the striata of ground squirrels in 5 phases of the hibernation cycle. Whereas levels of striatal DA and its deaminated metabolite DOPAC did not change significantly, the concentrations of the O-methylated-deaminated metabolite, homovanillic acid (HVA), decreased in all phases of hibernation relative to euthermia. Striatal 3H-spiperone binding sites declined across the hibernation cycle in parallel with the reduction of HVA concentration; receptor binding affinity was unchanged by arousal state. In conjunction with previously reported findings, these results are consistent with the hypothesis that hibernation is associated with a down-regulation of the postsynaptic D2 receptors secondary to increased extracellular DA concentration and reduced DA degradation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

The effects of buspirone on sleep in the rat.

Buspirone is a novel anxiolytic compound that does not produce the sedation often associated with the use of benzodiazepines. The present study evaluated the effects of this anxiolytic on sleep in rats surgically prepared for long-term recordings. Buspirone, at a dose of 3 mg/kg i.p., produced a significant increase in total wake time (P less than 0.05) compared with drug-free controls. At a dose of 10 mg/kg i.p., rats displayed altered sleep patterns with the most significant effects observed in the first third of recording period. These animals displayed increased wakefulness (P less than 0.001), decreased non-REM sleep (P less than 0.001), and an obliteration of REM sleep (P less than 0.02). These data support the suggestion that the clinically useful anxiolytic buspirone, unlike the benzodiazepines, does not induce sleep.

Animals↗
PubMed1986

Precision of circadian wake and activity onset timing in the mouse.

In each circadian cycle, a mouse begins its major activity period with discrete wake onset and activity onset events. The precision with which these events are timed in constant darkness was analyzed using the approach outlined by Pittendrigh and Daan (1976). Negative serial correlations of observed circadian period values (mean r1 = -0.471 for wake data, -0.409 for activity data) imply that deviations in period tend to be compensated by opposite deviations in the following cycle. As a result, precision of the circadian pacemaker must be better than that of observed rhythms. Standard deviation of the pacemaker period sigma(tau) was estimated at 5.1 min. Some individual data series had estimates s(tau) = 0, implying a nearly perfect pacemaker. Previous speculation was that wake onset would be under more direct pacemaker control than activity onset, and would therefore be timed more precisely (Pittendrigh and Daan 1976; Richardson et al. 1985). Contrary to this prediction, intervals between successive wake onsets exhibited significantly greater variance than intervals between successive activity onsets. Two possible interpretations of this finding were proposed.

Animals↗
PubMed1986

Sleep disturbance produced by electrical stimulation of the locus coeruleus in a human subject.

A 25-year-old man with a chronically implanted stimulating electrode placed in the region of the locus coeruleus (LC) was monitored for 5 nights in a sleep laboratory to study the role of the LC in sleep. Sleep patterns were compared between the 2 nights in which the stimulation was applied periodically every 90 min and the 2 nights in which no stimulation was applied. In contrast to the normal sleep patterns that occurred during the 2 nonstimulation nights, electrical stimulation of the LC produced a profound disruption of sleep and significant reductions in the total amounts of NREM sleep, REM sleep, REM sleep as a percent of total sleep (NREM + REM sleep), and total sleep. Results suggest that the LC has a role in maintaining normal sleep patterns.

Adult↗
PubMed1986

Evidence for excessive sleepiness in canine narcoleptics.

Six genetically narcoleptic dogs, as well as 6 age- and breed-matched control dogs, were recorded continuously for 24 h to compare sleep/wake patterns and to determine whether narcoleptic dogs exhibit evidence of excessive sleepiness. Compared with controls, the affected animals showed a substantial reduction in wakefulness and a significant increase in time spent in the drowsy state. Total NREM sleep and total sleep time (NREM and REM sleep) in the 2 groups, however, were very similar. Results suggest that, whereas genetically narcoleptic dogs show less wakefulness than controls, they are not hypersomnolent. However, the greater amounts of drowsiness in the affected animals suggest that they are 'sleepier' than controls. These results are highly consonant with those found in human narcolepsy.

Animals↗
PubMed1986

Dose-related effects of triazolam and flurazepam on a circadian rhythm insomnia.

Forty-eight normal subjects had sleep recordings and multiple sleep latency tests (an EEG measure of sleepiness) before and after a 12-hour shift of sleep-wake schedule. After 2 baseline days, subjects postponed sleep until 12:00 noon, then for three 24-hour periods were in bed from 12:00 noon until 8:00 PM. Treatment in parallel groups were administered before shifted sleeps. Sleep disturbance was greatest in the last quarter of shifted nights (6.5 to 8.5 hours after medication). Subjects taking placebo showed significant sleep loss on shifted nights and increased sleepiness the next day. Triazolam, 0.5 mg, reversed the sleep loss and consequent daytime sleepiness associated with the shifted sleep schedule. Triazolam, 0.25 mg, was not significantly better than placebo. In a dose-related manner, flurazepam mitigated the insomnia, but carryover effects left both dose groups more sleepy than were the placebo control subjects. Whether these laboratory results are applicable to clinically occurring forms of transient insomnia remains to be seen.

Adult↗