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Biomedical subjects

W B Mendelson

Publications and source records attributed to W B Mendelson.

At least 55 records · Page 3Linked to original sources
PubMed1995

The relationship of sleepiness and blood pressure to respiratory variables in obstructive sleep apnea.

As a follow-up to a previous assessment of complications of sleep-disturbed breathing in 265 patients, we have reevaluated measures of sleepiness and hypertension in patients with obstructive sleep apnea (OSA) (n = 518), central sleep apnea (n = 50), and subclinical sleep-disordered breathing (SDB) (n = 107). Both subjective and objective (multiple sleep latency test [MSLT]) measures indicated that OSA patients were sleepier than those with subclinical SDB. The OSA patients weighed significantly more than the patients with central sleep apnea or subclinical SDB. They had a higher proportion of men, described more habitual sleepiness, and had a higher likelihood of feeling unrefreshed in the morning compared with the group with subclinical SDB. Among the OSA patients, there was a significant correlation between subjective and objective assessment of sleepiness, but this relationship was quantitatively very small. A forward stepwise regression analysis revealed that weight, and to a lesser degree waking time after sleep onset, could account for 65.5% of the variance in subjective sleepiness. Seventy-five percent of the variance of the mean sleep latency in the MSLT could be accounted for by the mean minimum arterial oxygen saturation in non-REM sleep and the nocturnal sleep latency. Diastolic BP was significantly higher in OSA patients compared with the patients with central sleep apnea and subclinical SDB. When covarying for weight, age, and gender, this effect lost significance. Among OSA patients taken by themselves, 98.3% of the variance in diastolic blood pressure could be accounted for by the mean minimum arterial oxygen saturation in non-REM sleep, with very small additional contributions of apnea/hypopnea index, weight, and age. In summary, among patients across a spectrum of SDB, differences in diastolic BP were primarily associated with weight, age, and gender. Among OSA patients, perhaps because of a more limited variance in weight, diastolic BP was associated with measures of SDB.

Adult↗
PubMed1995

An assessment of short-acting hypnotics.

Insomnia, the experience of poor quality or quantity of sleep, is a very common complaint. Approximately 65 million adults (36% of the American population) complain of poor sleep, and of this group, 25% have insomnia on a chronic basis. These chronic insomniacs not only report higher rates of difficulty with concentration, memory and the ability to cope with minor irritations but also have 2.5 times more fatigue-related automobile accidents than do good sleepers. Despite its ubiquity, insomnia is often either untreated or inadequately treated. Short-acting hypnotics are advocated for transient insomnia, which lasts less than 3 weeks, and in patients with chronic insomnia as an adjunctive treatment where nonpharmacological treatment is not sufficient to alleviate insomnia and the related daytime detrimental effects. The putative adverse effects of hypnotics must be weighted against the severe health effects caused by continued sleep impairment. If hypnotic agents are used, they should be taken nightly only for brief use, or intermittently in longer term use. Benzodiazepines, zolpidem and zopiclone (in countries where the latter is available) remain the recommended hypnotic agents, although in the past few years there has been much criticism in lay magazines and on television about the use of benzodiazepines. However, this review of the efficacy and tolerability data of the short-acting hypnotics suggests that triazolam is comparable with other short-acting hypnotics at equipotent doses while taking into consideration that for every hypnotic, different study populations display different degrees of efficacy. In addition, contrary to previous suggestions that such adverse effects are rebound insomnia and anterograde amnesia are unique to triazolam, hypnotically equivalent doses of tirazolam have not been shown to produce these effects more frequently than other short-acting hypnotics. The newer nonbenzodiazepine hypnotics seem to be equally efficacious as the short-acting benzodiazepines; whether they will truly have a better adverse effect profile will be determined as more clinical experience accumulates. Despite the availability, relative safety and efficacy of these newer hypnotic agents, they should not be perceived as the sole treatment for insomnia and should be used in conjunction with nonpharmacological techniques (such as adherence to good sleep hygiene, sleep restriction, stimulus control and biofeedback therapy).

Adult↗
PubMed1995

Mean versus median for the multiple sleep latency test.

Since its introduction in the mid-1970s, the multiple sleep latency test (MSLT) has become the standard method for evaluating hypersomnolence. The mean sleep latency is usually calculated and constitutes the traditional basis for interpretation. Mean and median are both measures of the central tendency of a distribution, but because the trials of the MSLT are limited to 20 minutes, the median may be more appropriate. The objective of this study was to compare the value of the mean versus the median sleep latency in the interpretation of the MSLT. We retrospectively analyzed 100 MSLTs performed for evaluation of excessive daytime sleepiness. Patients' ages ranged from 6 to 84 years (mean 43). Mean and median sleep latencies were calculated according to standard formulas. We classified each record into one of three categories, using both the mean and the median sleep latencies: normal (> 10 minutes), moderate (> or = 5 and < or = 10 minutes), and severe sleepiness (< 5 minutes). Of the 100 MSLTs, 89 remained in the same category (normal, moderate, severe) whether mean or median was used. In 11 cases, the category changed. All shifts were by one category, that is, no shift occurred between normal and severe. This study suggests that, despite valid theoretical arguments for the use of the median, both measures are equally acceptable for clinical purposes.

Adolescent↗
PubMed1994

Sleep in fall/winter seasonal affective disorder: effects of light and changing seasons.

Disturbances of sleep are a hallmark of seasonal affective disorders (SAD), as they are of other mood disorders. Fall/winter SAD patients most often report hypersomnia. Among responses of 293 SAD patients on a symptom questionnaire, complaints of winter hypersomnia (80%) greatly exceeded insomnia (10%), hypersomnia plus insomnia (5%), or no sleep difficulty (5%). Increased sleep length in fall/winter is not unique to SAD. Among 1571 individuals across four latitudes surveyed at random from the general population, winter sleep increases of < or = 2 hr/day relative to summer were reported by nearly half. However, hypersomnia had a low correlation (r = 0.29) with the total number of other SAD symptoms that were reported in this sample. Ten SAD patients kept daily sleep logs across 1 yr that showed increases in fall and winter (sleeping most in October; least in May) whose maximum averaged 2.7 hr per day more weekend sleep than in spring and summer. These winter increases might have been somewhat attenuated since most received light therapy during part of the winter. Nocturnal EEG recordings of depressed SAD patients in winter showed decreased sleep efficiency, decreased delta sleep percentage, and increased REM density (but normal REM latency) in comparison with recordings: (1) from themselves in summer; (2) from themselves after > or = 9 days of light therapy; or (3) from age- and gender-matched healthy controls. Thus, the extent of fall/winter oversleeping recorded by our SAD patients did not differ dramatically from that reported by the general population, but sleep complaints of our SAD patients have been accompanied by features of sleep architecture that are different from healthy controls and are reversed by summer or by bright-light therapy.

Adult↗
PubMed1994

Nifedipine blocks effects of triazolam injected into the dorsal raphe nucleus on sleep.

In previous studies, the author has reported both in vitro and in vivo sleep studies in which there were complex interactions between benzodiazepine hypnotics and the dihydropyridine calcium channel blocker nifedipine. The author has also reported that microinjections of triazolam into the dorsal raphe nucleus of the rat result in enhancement of wakefulness. In the present study, nifedipine and triazolam were coadministered into this site. As previously was observed, triazolam produced a dose-dependent increase in sleep latency and a decrease in total sleep, primarily by reducing non-rapid-eye-movement sleep. Nifedipine had no effect on sleep when given by itself but prevented the alterations in sleep by triazolam. These various sleep effects were not associated with alterations in core temperature. These data are consistent with the view that aspect of the sleep-altering activity of triazolam involves interaction with voltage-dependent calcium channel activity.

Animals↗
PubMed1993

Sleep disturbance in chronic fatigue syndrome.

Sleep and fatigue characteristics were evaluated in 72 patients who met major criteria for the chronic fatigue syndrome (CFS), 57 multiple sclerosis (MS) patients preselected for fatigue complaints, and 40 healthy controls. Using previously validated rating scales, CFS patients had significant elevations in fatigue and sleep disturbance compared to the MS and healthy control groups. To confirm these subjective measures, polysomnography was carried out in a subgroup of CFS patients who included sleep disturbance as one of their symptoms on initial clinical interview. In 10 of 16 (62.5%) polysomnography revealed clinically significant and potentially treatable sleep abnormalities. Their sleep disorders included periodic movement disorder (4), excessive daytime sleepiness (3), apnea (2), and narcolepsy (1). We conclude that subjective sleep disturbance is common in CFS and some CFS patients may have objective sleep disorders.

Adult↗
PubMed1993

Do benzodiazepines induce sleep by a GABAergic mechanism?

In order to further characterize the possible role of GABA function in the sleep-inducing properties of benzodiazepines (BZs), we have administered the GABA agonist muscimol (0.05 and 0.1 mg/kg) and the GABA antagonist bicuculline (1.25 and 2.5 mg/kg) IP, alone and in combination with triazolam (0.8 mg/kg). There was no evidence of interaction of these compounds with triazolam vis a vis sleep. These data are consistent with an earlier report indicating a lack of interaction of muscimol with flurazepam, and suggest that non-GABAergic mechanisms may be involved in the hypnotic properties of benzodiazepines.

Animals↗
PubMed1993

Effects of triazolam and nifedipine injections into the medial preoptic area on sleep.

We have reported previously that microinjections of the benzodiazepine (BZ) hypnotic triazolam into the medial preoptic area (MPA) of the hypothalamus increase sleep in the rat. As a follow up to previous work, which has indicated that the dihydropyridine calcium channel blocker, nifedipine, prevents sleep induction by an intraperitoneally administered BZ, we have now coinjected nifedipine and triazolam into the MPA. It was found that nifedipine alone had no significant effects on sleep and prevented sleep induction by triazolam. There were no drug-specific effects on core temperature in any treatment condition. These data suggest that dihydropyridine-sensitive sites may be involved in the mechanism of sleep induction by BZs.

Animals↗
PubMed1993

Sedatives and suicide: the San Diego study.

Although clinical experience points to the frequent use of sedatives and hypnotics in suicide, remarkably few data are available to characterize the demographics of the population involved. The San Diego study, in which toxicological examinations were performed in over 90% of 204 consecutive suicides seen by the San Diego County Coroner during 1981-1982, provides an opportunity to examine suicide victims who were taking various medicines and drugs of abuse. Drugs were detected in 68% of tested subjects. Anxiolytics and hypnotics were found in 10.7% and 12.3% of the cases respectively. Women were more than 4 times as likely as men to have tested positive for an anxiolytic or hypnotic. Antidepressants were found in 5.9%. Alcohol had been ingested by 28.3% of subjects. Barbiturates and benzodiazepines were found in approximately equal proportions, although nationally the number of barbiturate prescriptions filled in drugstores was only one-sixth that of benzodiazepines. Major depression was found in 22.5%; among cases with positive histories of major depression, only a small proportion ranging from 4-10% were positive for antidepressants, anxiolytics or hypnotics. Interestingly, approximately equal proportions (4.8% and 6.2%) of depressed and non-depressed patients were positive for antidepressants. Among subjects whose deaths were attributed to drug ingestion, benzodiazepines, barbiturates and antidepressants were found in approximately one-third each, with little overlap. Although benzodiazepines were found in less than 10% of the group as a whole, they were found in one-third of subjects who committed suicide by overdose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Pharmacologic alteration of the perception of being awake or asleep.

In order to further explore the effects of triazolam on the subjective experience of sleeping, we awakened chronic insomniacs with an electronic tone at five points across the night after having administered placebo and three doses of triazolam (0.125, 0.25 and 0.375 mg). Triazolam reduced the likelihood of subjects reporting that they had been awake by about half. Drug effects were most evident in the period 5 minutes after "lights out", at which time there was a reduction in the certainty of the subjects' response; the investigator's ratings of mental activity on the dream complexity scale rose from a rating of "awake" following placebo to the borderline of sleep following triazolam. After triazolam administration, subjects reported less certainty about their descriptions of mental imagery. These data are consistent with a hypothesis that during sleep, and particularly at the threshold of electroencephalogram (EEG) defined sleep, triazolam induces cognitive changes in which the subjective distinction between waking and sleep becomes less clear. Several approaches are suggested to determine whether these effects are related to retrospective subjective reports of hypnotic efficacy.

Adult↗
PubMed1993

Insomnia and related sleep disorders.

Insomnia may result from a variety of causes, including pathophysiology of the cardiorespiratory system, medical or psychiatric disorders, medications, substance abuse, and circadian rhythm disturbances. When these many causes are excluded, there remains an interesting group of patients whose disorder is characterized either by learned sleep-preventing associations or by a dissociation between physiologic measures and the subjective experience of sleep. One approach to understanding the latter group is to examine the patient's perception of the experience of being awake or asleep as well as the effects of hypnotic medication on this process.

Attitude↗
PubMed1992

Characterization of the hypnotic effects of triazolam microinjections into the medial preoptic area.

We have previously reported that microinjections of the benzodiazepine hypnotic triazolam into the medial preoptic area (MPA) of the hypothalamus enhance sleep in rats. The present study further characterizes this effect, by examining its anatomical specificity, determining whether it is mediated by interaction with central benzodiazepine receptors, and assessing whether sleep induction is associated with changes in core temperature. It was found that microinjections of 0.25 and 0.5 micrograms triazolam into two nearby structures, the lateral preoptic area and diagonal band of Broca, failed to alter sleep. Total sleep time was enhanced by microinjection of triazolam into the MPA, and this effect was blocked by co-administration of the benzodiazepine receptor blocker RO 15-1788. Sleep enhancement by triazolam was not associated with significant alterations in core body temperature. These observations continue to suggest that the MPA may be a site which mediates the hypnotic effect of triazolam, and add to the growing body of data emphasizing the importance of hypothalamic function in the regulation of sleep and waking.

Body Temperature↗
PubMed1992

Sleepiness and hypertension in obstructive sleep apnea.

In order to assess the complications of sleep apnea, we have reviewed a data base of 619 consecutive admissions to a university sleep disorders center. Although patients with obstructive sleep apnea (OSA) described more subjective sleepiness than patients with central sleep apnea (CSA) or primary snoring (PS), the multiple sleep latency test (MSLT) indicated similar levels of physiologic sleepiness in the two apneic groups, which was greater than among those with PS. There was no significant relationship between individual subjective estimates of habitual sleepiness and the MSLT values. Among the OSA patients the mean minimum arterial oxygen desaturation during REM sleep accounted for 65 percent of the variance of the mean sleep latency on the MSLT, with an additional, smaller, contribution of the disordered breathing rate per hour. Subjective reports of sleepiness were associated with sleep efficiency and the number of disordered breathing events in NREM sleep. Patients with OSA or CSA had similar diastolic blood pressures and frequencies of history of treatment for hypertension, which were significantly higher in OSA than in the PS group. In the OSA group the absolute minimum arterial oxygen desaturation during NREM sleep was the most significant contributor to waking diastolic blood pressure, with an additional small contribution by weight. A history of treatment for hypertension was most strongly associated with weight, without significant additional contributions by measures of disordered breathing events or oxygen desaturation; however, weight was highly intercorrelated with measures of the apnea/hypopnea index and minimum arterial oxygen desaturation. In summary, these data support recent findings which show a close relation of obesity to a history of hypertension in OSA, and extend to this group a previous observation that in regular heavy snorers, there may be a disparity between levels of physiologic and subjective sleepiness.

Analysis of Variance↗
PubMed1992

Neuropharmacology of sleep induction by benzodiazepines.

Although benzodiazepines (BZs) have been the most widely used sedative/hypnotics for many years, the mechanism by which they induce sleep and the neuroanatomic site(s) at which they act have remained poorly understood. Recent characterization of the central BZ-GABAA receptor complex using molecular biological techniques and sleep studies employing new ligands have begun to elucidate these issues. Although alterations in GABAergic activity are involved in the anticonvulsant and myorelaxant properties of BZs, the significance of GABA function in their hypnotic effects is less clear. The pharmacologic significance of receptor subtypes also remains uncertain. A growing body of evidence indicates that the hypnotic effects of BZs involve alterations in potential-dependent calcium ion flux. In terms of neuroanatomy, BZ effects on sleep may result from actions in the anterior hypothalamus as well as brainstem structures including the dorsal raphe nuclei.

Animals↗