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Biomedical subjects

T Roth

Publications and source records attributed to T Roth.

At least 145 records · Page 8Linked to original sources

Uvulopalatopharyngoplasty. One-year followup.

Uvulopalatopharyngoplasty (UPPP), originally evaluated in 66 patients with objectively documented sleep apnea syndrome, was successful in 33 of the patients as indicated by clinical and polysomnographic improvements. One-year followup polysomnographic evaluations were obtained in 20 of these patients; the remaining 13 were lost to followup. After one year, the patients maintained the improvements seen at the six-week evaluation. Frequency and duration of apnea was significantly reduced from presurgery levels and similar to the six-week results. Oxygenation measures also did not differ from the six-week results, remaining better than presurgery values. Thus, respiration did not disrupt sleep to the degree it had before surgery. Sleep measures were improved compared to presurgery and similar to the six-week data. Body weight remained stable over the entire period.

Female

Sustained performance with short evening and morning sleeps.

The effect which early evening sleep may have on overnight and subsequent daytime performance, and the effect which morning sleep may have on daytime performance after overnight sleep deprivation has been studied in six healthy male volunteers. It would appear that relatively short periods of natural and drug induced (brotizolam 0.125 mg) sleep have a beneficial effect on subsequent performance even in the absence of preceding sleep debt. In the event of disturbed sleep in shiftwork an hypnotic may be helpful, and in this context, one which is rapidly eliminated and sustains sleep is appropriate.

Adult

Hypnotics and aircrew.

The management of sleep difficulties which arise during air operations must be related, at least initially, to the cause, but the aeromedical specialist is frequently faced with the possible use of hypnotics. There are no simple guidelines, but an understanding of various issues will help toward the effective use of these drugs in those who have to cope with irregularity of rest and carry out skilled work. Some knowledge of the pharmacokinetics of the drugs concerned is useful as persistence of effect and the potential for accumulation with repeated ingestion are important factors, while efficacy in relation to sleep of different durations and at unusual times must also be considered.

Adult

Treatment of a 12-hour shift of sleep schedule with benzodiazepines.

Normal sleepers underwent sleep recordings and daytime tests of sleep tendency, performance, and mood while being shifted 180 degrees in their sleep-wake schedule. After two baseline 24-hour periods, subjects postponed sleep until noon. For the next three 24-hour periods, they were in bed from 1200 to 2000 and received triazolam, flurazepam, or placebo at bedtime in parallel groups. Placebo subjects showed significant sleep loss after the shift. Active medication reversed this sleep loss. Despite good sleep, flurazepam subjects appeared most impaired of the three groups on objective assessments of waking function; triazolam subjects were least impaired.

Adult

Polysomnographic and MMPI characteristics of patients with insomnia.

This report represents the polysomnographic aspects of sleep and the psychological characteristics of a large series of patients with insomnia classified according to the diagnostic system of the Association of Sleep Disorders Centers. The findings for patients in the various diagnostic categories were compared to those of symptomatic patients with no objective findings. 9 specific diagnoses were made, but 4 diagnoses accounted for the majority of patients. The 4 most prevalent were psychophysiological disorders (15%), psychiatric disorders (17%), nocturnal myoclonus and restless legs (18%), and no objective findings (19%). Patients of a sleep disorders center are a select population and may not be representative of the general population of patients with insomnia complaints. The psychological characteristics of the different diagnostic groups were assessed by computing the number of elevations on the MMPI. Patients with a psychiatric diagnosis exhibited the highest number of MMPI elevations, as might be expected. Patients with nocturnal myoclonus had the lowest number of elevations. The other groups did not significantly differ from the group with no objective findings. Polysomnographic measures of sleep differed considerably among the diagnostic groups. The groups with medical disorders, respiratory impairment, atypical polysomnographic features, and nocturnal myoclonus had similar short sleep latencies to those of the group with no objective findings. With longer wake times before sleep and significantly different from patients with no objective findings were the psychophysiological disorder, psychiatric disorder and drug and alcohol groups. Patients with a circadian rhythm disturbance had the longest latencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm

Amnesic effects of lormetazepam.

Sixteen healthy men, age 18-35, each received lormetazepam (1.5 mg), flurazepam (30 mg), temazepam (30 mg) and placebo (double-blind in a Latin Square design) 30 min before bedtime for 2 consecutive nights followed by a 12 day washout between conditions. Three hours after drug (2.5 h after bedtime) subjects were awakened and administered a 16-item memory task. Fifteen minutes after the awakening subjects returned to bed, were instructed to go to sleep, and remained in bed for an additional 5.5 h. Immediately after the memory tasks, before returning to bed, subjects recalled almost all of the 16 items when placebo was administered before bedtime. Immediate recall was significantly poorer than placebo after temazepam and flurazepam, but not after lormetazepam. Morning recall was reduced significantly from the immediate nighttime level in each condition; this loss was smallest with placebo. All active drug conditions produced significantly greater amnesia than placebo. This amnesia was smallest after lormetazepam and greatest after temazepam, which differed significantly from each other. All active drugs significantly reduced latency measures of the return to sleep after the 15 min awakening; it was shortest with temazepam and longest with flurazepam. This study showed a relation between the hypnotic and amnesic effects of these drugs which is consistent with their pharmacokinetic properties.

Adolescent

Sleep fragmentation and daytime sleepiness.

It has been noted that clinical populations complaining of excessive daytime sleepiness (EDS) frequently have disrupted or fragmented nocturnal sleep. The relation between sleep fragmentation and daytime sleepiness has not been systematically studied. This study was designed to use correlational techniques evaluating the relation between these variables in patients complaining of EDS, patients complaining of insomnia, and asymptomatic controls. The four groups studied included patients complaining of EDS with sleep apnea (n = 15) or with periodic leg movements (n = 15), patients complaining of insomnia (n = 15), and healthy volunteers with no sleep complaint (n = 10). One night of polysomnography followed by a Multiple Sleep Latency Test was obtained for each subject. Each recording was evaluated using standard criteria and also by a four-level arousal scoring system. Across all subjects, the total number of arousals correlated significantly with sleepiness index (r = 0.48, p less than 0.001). Closer analysis of the data shows that, depending upon the sleep complaint, different types of arousals are predictive of degree of daytime sleepiness. It is concluded that the number and type of nocturnal arousals play an important role in subsequent daytime sleepiness.

Adult

Daytime sleepiness and antihistamines.

A daytime nap procedure was used to evaluate the daytime sleepiness associated with antihistamines, as well as to assess their hypnotic potential. Healthy, normal subjects received diphenhydramine (150 mg), terfenadine (120 mg), and placebo and went to bed at 900, 1100, 2000, and 2200 h with the instruction to try to fall asleep. The remained in bed for 60 min while standard sleep recordings were made. Across all conditions latency to stage 1 sleep increased significantly from nap 1 to nap 4 and the amount of sleep (all nonstage 1 sleep) decreased significantly. Over the four naps the mean latency to stage 1 sleep with diphenhydramine was significantly shorter than terfenadine and placebo, which did not differ. On the other hand, there were no differences among the drug conditions in the amount of nonstage 1 sleep. In sum, diphenhydramine at this dose produces sleepiness but shows little potential as a hypnotic, and accumulated sleep across the day makes people progressively more alert.

Adult

Periodic movements during sleep, sleep fragmentation, and sleep-wake complaints.

To better understand the relation of sleep complaint to sleep continuity and periodic movements during sleep (PMS), two groups of patients were studied retrospectively. One group of 51 patients, 26 men and 25 women, with a mean age of 56.4 years, complained of insomnia. The other group of 29 patients, 20 men and nine women, with a mean age of 55.8 years, complained of excessive daytime sleepiness. Sleepy patients differed significantly from insomnia patients in that they fell asleep faster and slept longer. They showed more frequent arousals (shifts to stage 1 sleep and number of awakenings) than insomnia patients who had longer arousals (mean duration of awakenings). Insomnia patients had more series of PMS, but sleepy patients had more PMS bursts per series.

Arousal

Temazepam's efficacy in patients with sleep onset insomnia.

The hypnotic efficacy of temazepam capsules (30 mg) was studied in twelve patients who had objective polysomnographic evidence of sleep onset insomnia. Patients slept in the laboratory, retiring at their usual bedtime after taking placebo or temazepam 30 min earlier, and were monitored for 8 h using standard polysomnographic techniques. Acute (nights 5-7) and chronic (nights 11-13) temazepam improved the sleep of these patients by reducing sleep latency and increasing sleep time compared to the placebo baseline (nights 2-4). No detrimental effects on daytime function the following morning were observed using questionnaires and objective tests of performance. No consistent evidence of disturbed sleep after discontinuation of treatment was obtained over three recovery nights.

Adult

Benzodiazepines and memory.

Benzodiazepines possess anterograde amnesic properties, disrupting both short-term and long-term memory function. The amount of amnesia is systematically related to dose effects and half-life differences among the benzodiazepines. Memory deficits are found for episodic, semantic, and iconic memory function. The deficits in long-term memory are probably the result of a disruption of consolidation of information in memory and not retrieval from memory. The disruption is produced by rapid sleep onset. Thus the long-term amnesia is really a retrograde effect of sleep and not the anterograde effect of the drug.

Amnesia

Effects of a single dose of flurazepam on the sleep of healthy volunteers.

We compared the effects of a single dose of flurazepam (Dalmane) 45 mg with placebo on the sleep of twelve young, healthy male volunteers. A double-blind random-order cross-over design was used. Flurazepam 45 mg had no effect on sleep latency to stage 1 or to stage 2 sleep and no effect on percent stages 3 and 4 sleep. Total sleep time and percent stage 2 sleep significantly increased on the drug night, while wake time, percent stage 1, and percent REM decreased. It is hypothesized that decreases in stages 3 and 4 that are generally seen on second administration or withdrawal of flurazepam are due to the major metabolite, N-desalkyl-flurazepam. In addition, respiration was recorded in six subjects. The number of NREM apneas increased from 15 on the placebo night to 29 on the drug night, although this was not statistically significant. The effect of flurazepam and other benzodiazepines on respiration deserves further study.

Adolescent

Night-to-night consistency of apneas during sleep.

The consistency of apneas from night to night was examined in 2 groups of patients. The first group had more than 100 apneas per night (frequent apnea) and the second group had less than 100 apneas per night (infrequent apnea). All patients underwent clinical polysomnography for 2 nights, with no significant weight change or treatment occurring between recordings. The frequent apnea group showed a consistent number of apneas on the 2 nights (r = 0.92, p less than 0.01), whereas the infrequent apnea group showed a highly variable number of apneas (r = 0.35, p greater than 0.10). The correlations on apnea index (apneas per hours of sleep) showed a similar result. Apnea duration and type were consistent in both groups of patients.

Humans

Daytime sleepiness as a criterion in hypnotic medication trials: comparison of triazolam and flurazepam.

Sleep laboratory hypnotic medication trials typically determine efficacy by examining changes in polysomnographically recorded sleep. We introduce the use of daytime sleepiness, as assessed by the Multiple Sleep Latency Test (MSLT), as a criterion for daytime functioning in such trials. Two benzodiazepine hypnotics, triazolam (0.5 mg) and flurazepam (30 mg), with short and long half-lives respectively, were compared in a multicentered, double-blind crossover study. Results indicated these medications had virtually indistinguishable nocturnal effects, but differed dramatically during the day. Flurazepam decreased sleep latency on the MSLT, whereas triazolam did not. These results could indicate that daytime sleepiness is a concomitant effect of flurazepam.

Adult

Excessive daytime sleepiness associated with insufficient sleep.

Chronic insufficient sleep as an identifiable cause of excessive daytime sleepiness was investigated post hoc by comparing a series of patients with this diagnosis with patients with narcolepsy. Among the prominent features differentiating patients with insufficient sleep from patients with narcolepsy was the report, obtained on the sleep history, of a disparity between the reported amount of sleep obtained on weekdays versus weekends. On evaluation in the laboratory, patients with insufficient sleep showed atypically high sleep efficiency at night and a prolonged sleep time (longer than they report sleeping on a weekday night at home). Compared with patients with narcolepsy, they show a somewhat elevated percentage of stage 3-4 and REM sleep, although this is probably not higher than that of age-matched controls. On the Multiple Sleep Latency Test they displayed moderate sleepiness and no sleep onset REM periods. A mental status examination and Minnesota Multiphasic Personality Inventory did not suggest a primary psychiatric disorder.

Adult

Sleep laboratory and performance evaluation of midazolam in insomniacs.

This study evaluated laboratory sleep and performance after placebo, after 5, 10 and 20 mg of midazolam and after 30 mg of flurazepam. EEG recordings showed that 20 mg of midazolam significantly decreased sleep latency and stage 1 sleep, increased stage 2 sleep, and delayed the onset of the first REM period when compared with placebo. Subjective reports from the patients showed that the dose decreased the frequency of awakenings. In the morning, 9 h after drug ingestion, performance on most tests was affected very little by 20 mg of midazolam. However, performance on two psychomotor tests was slightly impaired after 20 mg of midazolam, while a test of free recall was slightly improved. On most variables, 5 mg of midazolam acted like placebo, while 10 mg of midazolam was intermediate between placebo and 20 mg of midazolam. Preliminary data suggest that 20 mg of midazolam may be as efficacious in inducing sleep as 30 mg of flurazepam, but may show fewer performance decrements in the morning.

Adult

Effects of acute administration of brotizolam in subjects with disturbed sleep.

Effects of ingestion of brotizolam (0.25 and 0.50 mg) over 1-3 days on polysomnographic measures of sleep were assessed in patients complaining of insomnia. Brotizolam reduced latency to sleep, number of awakenings and wake during sleep, and increased total sleep time. It also increased stage 2 sleep and decreased slow wave and rapid eye movement sleep. Increasing the dose from 0.25 to 0.50 mg increased hypnotic efficacy, and there was a more consistent and reliable effect. Discontinuation of brotizolam had minimal effects on sleep compared with placebo over the 3 nights after acute administration. No side-effects or disruption of daytime function was found using questionnaires and objective tests of performance.

Adult