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Biomedical subjects

A Zwyghuizen-Doorenbos

Publications and source records attributed to A Zwyghuizen-Doorenbos.

12 recordsLinked to original sources

Sedative effects and plasma concentrations following single doses of triazolam, diphenhydramine, ethanol and placebo.

Twelve, healthy, young men received 0.25 mg triazolam and ethanol placebo, 50 mg diphenhydramine and ethanol placebo, 0.6 g/kg ethanol and placebo pill and ethanol placebo and placebo pill in a double-blind Latin Square design. Each of the four treatments were administered for 2 days at 0900 hours with blood samples drawn on day one at 0830, 1030, 1230, 1430 and 1630 hours, and sleep latency and performance assessed on day two at 1000, 1200, 1400 and 1600 hours. Significant sedative effects of ethanol, triazolam and diphenhydramine relative to placebo were observed on the sleep latency and performance measures with the effects being detected over the full 6.5 hours of assessment. Among the active drugs, triazolam and diphenhydramine had similar sedative effects which differed from that of ethanol. Plasma concentration of each drug declined significantly over the 6.5 hours. Ethanol reached zero, but triazolam and diphenhydramine did not. Continued sedation (sedative effects after plasma concentration reached zero) was observed with ethanol.

Adult↗

Sedating effects of ethanol and time of drinking.

Ethanol (0.5 g/kg) was administered to 12 healthy, normal-sleeping men, aged 21 to 45, at two different times of the day (0900 and 1700 hr). The Multiple Sleep Latency Test (MSLT) was conducted at 1000, 1200, 1400, and 1600 hr in the day drinking condition and at 1800, 2000, 2200, and 2400 hr in the evening drinking condition. On placebo, sleepiness was greater in the daytime testing hours than in the evening, replicating findings on the circadian rhythm of sleepiness/alertness. There was a time of drinking (day versus evening) by ethanol interaction. An ethanol effect on sleep latency was found in the daytime hours, when alertness was relatively low. Ethanol failed to have a significant effect on sleep latency during the evening hours when alertness levels were increasing. Performance on a divided attention task, administered 1 hr postconsumption, was impaired by ethanol consumption, but did not vary as a function of time of drinking (day versus evening). However, at 5 hr postconsumption, mean reaction time on the first 20 min of a 40-min auditory vigilance task was slowed by ethanol to a greater extent after day drinking then after evening drinking.

Adult↗

Alerting effects of caffeine after normal and restricted sleep.

To assess the alerting effects of caffeine after normal and restricted nocturnal sleep, 36 healthy, nonsmoking men, 19 to 35 years old, who reported normal sleep and daytime alertness received 0, 75, or 150 mg caffeine twice daily after 8 and 5 hours in bed the previous night. Sleep restriction reduced average daily sleep latency measured by the Multiple Sleep Latency Test (MSLT) and slowed auditory vigilance reaction time in the latter half of the 40-minute task. Caffeine (75 and 150 mg) increased average daily sleep latency and improved vigilance reaction time. However, sleep restriction did not alter the alerting effects of caffeine. The data show that, unlike ethanol, basal level of sleepiness/alertness does not interact with the effects of caffeine.

Adult↗

Effects of caffeine on alertness.

The alerting effects of caffeine were assessed using a standard physiological measure of daytime sleepiness/alertness, the Multiple Sleep Latency Test (MSLT). Healthy young men (n = 24) were randomly assigned to receive caffeine 250 mg or placebo administered double blind, at 0900 and 1300 hours on each of 2 days. On the 3rd day both groups received placebo to test for conditioning to the alerting effects of caffeine. Each day sleep latency was measured at 1000, 1200, 1400, and 1600 hours and performance (divided attention at 1030 hours and auditory vigilance at 1430 hours) was assessed. Caffeine increased sleep latency (i.e., improved alertness) and auditory vigilance performance compared to placebo. Tolerance to the effects of caffeine on sleep latency developed over the four administrations. On the conditioning test (day 3) the group receiving caffeine the previous two days was more alert and performed better than the placebo group.

Acoustic Stimulation↗

Polysomnographic, performance, and personality differences of sleepy and alert normals.

The nocturnal sleep, performance, and personality of healthy, asymptomatic, normal young men, 18 who had unusually short sleep latencies on the Multiple Sleep Latency Test (average latency, less than or equal to 6 min) and 20 with unusually long latencies (average latency, greater than or equal to 16 min) were compared. On the nocturnal sleep recording, sleepy subjects had a shorter sleep latency, less waking time, and overall greater sleep efficiency than alert subjects. During the day, sleepy subjects performed more poorly than alert subjects on divided attention and vigilance performance tasks. The sleepy and alert subjects did not differ appreciably on the Minnesota Multiphasic Personality Inventory and Jenkins Activity measures of personality. On the Institute of Personality and Ability Testing Anxiety Scale, the sleepy subjects showed higher levels of anxiety than the alert subjects. The data were interpreted as indicating that the sleepy subjects had a sleep debt due to chronic sleep restriction.

Adult↗

Individual differences in the sedating effects of ethanol.

Twenty-four healthy, normal-sleeping, males aged 21-35 were screened for basal levels of sleepiness using the Multiple Sleep Latency Test (MSLT). Twelve subjects had basal average daily sleep latencies of less than or equal to 6 min (sleepy) and 12 had latencies of greater than or equal to 16 min (alert) on the MSLT. Subjects consumed either ethanol (0.75 mg/kg) or placebo at 0900-0930 after spending 8 hr time in bed (TIB) the previous night. Sleep latency was measured at 1000, 1200, 1400, and 1600 hr. Divided attention performance and the Stanford Sleepiness Scale (SSS) were assessed at 1100 hr. Breath ethanol concentration (BEC) was determined prior to each latency test. Ethanol decreased average daily sleep latency, divided attention scores and SSS ratings. There were individual differences in the sedating and impairing effects of ethanol, related to subjects' basal level of sleepiness/alertness. The alert subjects exhibited longer sleep latencies and higher performance scores after ethanol administration than the sleepy subjects after placebo. Subjectively the groups had a similar level of sleepiness on placebo and were similarly sedated with ethanol.

Adult↗

Sleep extension, enhanced alertness and the sedating effects of ethanol.

Twelve, healthy young men (mean age 25.6 years) consumed either ethanol (0.75 g/kg producing a peak breath ethanol concentration, BEC, of 0.060% on average) or placebo at 0900-0930 hr after spending 8 hr time-in-bed (TIB) the previous night and once again after 7 or 8 consecutive nights of 10 hr TIB. Latency to sleep onset (on the Multiple Sleep Latency Test, a standard measure of daytime sleepiness/alertness) was tested at 1000, 1200, 1400 and 1600 hr and divided attention performance was assessed at 1100 hr. Ethanol reduced sleep latency and divided attention performance and the sleep extension improved both sleep latency and divided attention performance. Sleep extension attenuated the sedating effects of ethanol; sleep latency after extending sleep did not differ between placebo and ethanol. While the effects of ethanol on performance still were detectable after sleep extension, the level of performance was at the 8-hr TIB placebo level. BEC peak and decline (determined before each latency test) did not change with the sleep extension. Hence, reduced BECs do not account for the reduction in the disruptive effects of ethanol with sleep extension.

Adult↗

Sleep extension in sleepy and alert normals.

Twenty-four healthy, young (21-35 years old) men with no complaints of daytime sleepiness, no habitual napping, and polysomnographically verified normal nocturnal sleep extended their time in bed (TIB) to 10 h for 6 consecutive nights to assess the effects of sleep extension on daytime sleepiness and performance. Twelve subjects had basal average daily sleep latencies of less than or equal to 6 min on the Multiple Sleep Latency Test and 12 had latencies of greater than or equal to 16 min before TIB was extended. The sleep extension improved daytime sleepiness differentially in the two groups. The degree of improvement was greater in the sleepy subjects than the alert subjects and the pattern of improvement differed between the groups. Sleepy subjects showed an immediate and uniform increase in alertness, while alert subjects did not show improvements until late in the extension. However, sleepy subjects never achieved the baseline level of sleepiness/alertness seen in the alert subjects.

Adult↗

Sleep and memory.

Generally sleep is considered a time of amnesia. It is not uncommon for an individual to experience 8 h of sleep and have no memory for events during that time. Similarly, a substantial proportion of the population has no memory for dreams that occurred during the night, despite the fact that the literature on awakening during rapid eye movement (REM) sleep clearly shows that individuals normally have four to six "dream experiences" a night. Research on this issue seems to indicate that the lack of memory cannot be explained by the organisms' inability to perceive stimuli. The data indicate that although perceptual thresholds are elevated, organisms can clearly perceive stimuli, and, in fact, can discriminate between them during sleep. The amnesia also cannot be explained by a defect in long-term memory, as studies have indicated that stimuli put into the memory during wakefulness are more efficiently retrieved after a sleep period than after a comparable period of wakefulness. The most likely explanation for the amnestic property of sleep seems to be the inability of organisms to transfer information from short-term memory to long-term memory during sleep. There are several sources of evidence to support this hypothesis. First, the probability of remembering a stimulus given during wakefulness is related to the proximity of sleep onset to the stimulus. Generally, information put into the system within 5 min of sleep onset is lost from memory. Secondly, disorders of excessive daytime somnolence which cause individuals to have frequent microsleeps are often associated with complains of memory problems.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Reversal by caffeine of triazolam-induced impairment of waking function.

Twelve, healthy normal men aged 21-25 years received each of four treatments (triazolam placebo plus caffeine placebo, triazolam 0.50 mg plus caffeine placebo, triazolam 0.50 mg plus caffeine 4 mg/kg, triazolam 0.50 mg plus caffeine 8 mg/kg), double blind, in a Latin-Square design. Triazolam or placebo was administered at 0830 and caffeine or placebo at 1000 and 1245. On two memory tasks, administered at 1015 with an immediate recall and a delayed recall at 1230 following a 90 min nap (1030-1200), both immediate and delayed recall was impaired by triazolam. Neither caffeine dose reversed the impairments. Sleep latency and sleep efficiency were improved by triazolam and not reversed by caffeine. On a performance battery presented at 1300 most measures of performance were impaired by triazolam; in general the caffeine dose of 4 mg/kg partially reversed the effect while the dose of 8 mg/kg completely restored performance.

Adult↗

Test-retest reliability of the MSLT.

The test-retest reliability of the Multiple Sleep Latency Test (MSLT) was evaluated in 14 healthy normal subjects. Each slept a single night in the laboratory (8 h time in bed) and received the MSLT the following day (1000, 1200, 1400, and 1600 h) on two occasions separated by 4-14 months. Mean sleep latency (four tests) was highly reliable from MSLT to MSLT (r = 0.97, p less than 0.001). The test-retest reliability did not change as a function of the interval of time between tests or as a function of the level of sleepiness (range = 4-20 min) within the population. However, as the number of tests comprising the MSLT was reduced below three, the reliability was reduced such that only 50% or less of the variance could be predicted.

Adult↗

Increased daytime sleepiness enhances ethanol's sedative effects.

Thirty healthy men, 21 to 35 years old, received either 8.7, 13.0 or 17.4 mmol/kg (0.4, 0.6, or 0.8 g/kg) ethanol after 8 hours time in bed (TIB), one night of 5 hours TIB, and four nights of 5 hours TIB. Ethanol, administered as 80-proof vodka mixed 1:4 with tonic water, was consumed over 30 minutes (0900 to 0930 hours). Sleep latency was measured at 1000, 1200, 1400, and 1600 hours using standard sleep laboratory methodology. Breath ethanol concentration (BEC) was determined prior to each latency test. Mean latency to sleep on the four tests decreased from day 1 (8 hours TIB) to day 5 (fourth day of 5 hours TIB). On day 1 mean latency after 8.7 mmol/kg differed from that after 17.4 mmol/kg, with the 13.0 mmol/kg latency intermediate between the other two. On day 2 and day 5 during sleep restriction these dose differences were diminished. Latency on day 5 after 8.7 mmol/kg was similar to that of 13.0 mmol/kg on day 2, which was similar to that of 17.4 mmol/kg on day 1. The BEC did not change from day 1 to day 5 and significant dose differences between each dose remained consistent from day to day. These data show that increased basal levels of sleepiness enhance ethanol's sedative effects for even moderate ethanol doses.

Adult↗