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Biomedical subjects

W B Mendelson

Publications and source records attributed to W B Mendelson.

At least 19 recordsLinked to original sources
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↗
PubMed1992

A comparison of sleep-disordered respiration in ESRD patients receiving hemodialysis and peritoneal dialysis.

STUDY OBJECTIVE: To compare sleep-disordered respiration in ESRD patients receiving peritoneal dialysis and hemodialysis. DESIGN: Subjective and objective measures of sleep were recorded in two groups of ESRD patients receiving PD and HD. SETTING: Tertiary-referral university hospital PATIENTS AND METHODS: Fifteen PD patients (12 males, 3 females) and 15 HD patients (11 males, 4 females) were studied for two nights in the sleep laboratory. RESULTS: Ten of the 15 PD patients and 8 of the 15 HD patients reported multiple types of sleep difficulties (NS). In the PD group, seven described substantial difficulty initially going to sleep; ten were troubled by awakenings during the night, while seven suffered from daytime sleepiness. In the HD group, seven described substantial difficulty initially going to sleep; eight were troubled by awakenings during the night, while five experienced day-time sleepiness. No significant difference was observed in total sleep time, intermittent wake time, sleep latency, sleep efficiency, total disordered breathing events, minimum oxygen saturation and periodic leg movements between the PD and HD groups. Sleep apnea was noted in 9 of 15 PD and 8 of 15 HD patients. CONCLUSIONS: This study indicates that the incidence and severity of sleep apnea is similar in ESRD patients receiving chronic peritoneal dialysis and hemodialysis.

Female↗
PubMed1992

Clinical distinctions between long-acting and short-acting benzodiazepines.

After their clinical introduction in the 1960s, the benzodiazepines rapidly became the most widely prescribed sedative/hypnotics because of their many advantages over barbiturates and other older agents. Along with this popularity came controversy, which has continued to this day. The most recent form this has taken has been the concern that the short-acting benzodiazepines may have a predisposition to induce certain forms of clinical complications. The author reviews the historical framework in which this controversy arose. In the late 1970s and early 1980s, it became increasingly clear that long-acting agents were associated with daytime sedation as well as cognitive and psychomotor impairment, particularly in the elderly. The short-acting benzodiazepines, which greatly reduced the frequency of these types of effects, rapidly became the most widely prescribed agents. A growing body of data indicates that the short-acting hypnotics are less likely to be associated with falls and hip fractures in the elderly and also have less respiratory depressant qualities, compared with the older long-acting agents. The short-acting compounds may also be more efficacious in inducing sleep during the first night of administration. In contrast, the long-acting agents may be more desirable in those cases in which daytime sedation is desired and may be associated with a delayed and milder withdrawal sleep disturbance. With the short-acting agents, however, sleep disturbance upon drug cessation is dose dependent and may be greatly reduced by tapering the dose.

Accidental Falls↗
PubMed1992

Sleep related respiratory disorders in end-stage renal disease patients on peritoneal dialysis.

STUDY OBJECTIVE: To assess the possible effects of peritoneal dialysis (PD) on sleep-related respiration, which might result from dialysate bulk load in the abdomen and/or alterations in metabolic control of respiration during sleep. DESIGN: Subjective and objective measures of sleep were prospectively compared on randomly assigned nights with PD fluid (2.0 L) and without PD fluid in the peritoneal cavity in 11 end-stage renal disease (ESRD) patients on PD. SETTING: Tertiary-referral university hospital. PATIENTS AND METHODS: Fifteen consecutive patients on peritoneal dialysis who complained of chronic sleep disturbance and requested sedative were selected. Four patients declined polysomnographic studies. Consequently, 11 ESRD patients (8 males and 3 females) with a mean age of 63 +/- 4 (SEM) years were studied. RESULTS: Eight of the 11 patients reported multiple types of sleep difficulties. Polysomnographic recordings revealed significant primarily obstructive sleep apnea in 6 of 11 patients on at least 1 of 2 nights. Arterial blood pH, paO2, and paCO2 did not differ between nights with and without PD fluid in the peritoneal cavity in the group as a whole. In the 6 patients with sleep apnea, PaO2 was significantly lower (p less than 0.05) during the night with (PaO2 = 78 +/- 7 mmHg) than during the night without PD fluid (PaO2 = 92 +/- 4 mmHg). In the apneic patients, the amount of dialysate drained in the morning was negatively correlated with the minimum arterial oxygen saturation during the night (r = -0.94; p less than 0.005). CONCLUSIONS: This study indicates a significant relationship between PD patients with chronic sleep disturbance and sleep apnea syndrome. These data suggest that apneic patients may be susceptible to complications of dialysate bulk effect on oxygen desaturation.

Female↗
PubMed1991

An overview of chronic fatigue syndrome.

BACKGROUND: Psychological and immunologic factors both appear to contribute to chronic fatigue syndrome (CFS). By comparing CFS with other disorders in which fatigue is a prominent symptom, the association between fatigue, psychological vulnerability, depression, and immune function may be further defined. Recent data from psychological, neurologic, and immunologic studies that address these issues are reviewed. METHOD: Articles and abstracts covering CFS and related topics of fatigue, depression, and postinfectious syndromes were identified through MEDLINE and Index Medicus (1980-1990) and by bibliographic review of pertinent review articles. RESULTS: The 1988 definition of CFS by the Centers for Disease Control encompasses several conditions in which the major characteristic is severe fatigue associated with constitutional symptoms. Several studies have identified immune dysfunction in CFS patients, but the specificity of these findings remains unclear. Most studies have shown that CFS patients, compared with other patients with chronic medical illness, experience more disabling fatigue. Some investigators have found a higher incidence of concurrent and past psychiatric illness in CFS patients compared with other medical patients, thereby suggesting an underlying psychopathology in CFS. However, other studies have not found a higher than expected incidence of past depression in CFS patients and have further shown that many CFS patients have no identifiable psychopathology. CONCLUSION: CFS appears to be a heterogenous entity. Although there may be a high coincidence of major depression in CFS, a substantial proportion of patients lack any identifiable DSM-III-R psychiatric disorder yet still manifest the syndrome, thereby suggesting it has an autonomous entity. Despite the evolving nature of our current understanding of CFS, a rational diagnostic and therapeutic approach to CFS is possible.

Comorbidity↗
PubMed1990

Effects of muscimol and flurazepam on the sleep EEG in the rat.

In order to assess the possible role of GABA receptor function in the hypnotic property of benzodiazepines, we have examined the sleep EEG in rats given the GABA agonist muscimol, alone and in combination with flurazepam. Muscimol 0.05 and 0.1 mg/kg IP failed to alter sleep latency or total sleep time, and did not interact with the sleep-enhancing properties of flurazepam 20 mg/kg IP. These observations, in conjunction with a previous study of bicuculline, suggest that the hypnotic property of benzodiazepines may not be mediated by alteration of GABAergic activity.

Animals↗
PubMed1990

The search for the hypnogenic center.

1. Electrophysiological and lesion studies have suggested that a number of specific sites in the brainstem and basal forebrain may be involved in the regulation of sleep and waking. In contrast, a study of glucose consumption as measured by the 2-deoxyglucose technique reported a generalized decrease in nonREM sleep compared to waking. The rate of protein synthesis was relatively unchanged in nonREM sleep. 2. Another approach to understanding sleep regulation is to study the mechanism by which hypnotic drugs affect the nervous system. This may be done at both a molecular and neuroanatomic level. Studies with B-carbolines, inverse agonists of benzodiazepines (BZs), indicate that sleep induction by BZs is mediated by binding at the BZ recognition site of the BZ receptor complex. Binding at this site by a long-acting B-carboline parallels the time course of its arousing effects. A study with an enantiomeric BZ indicates that the effects on sleep are stereospecific. It is conceivable that some inverse agonists or enantiomeric benzodiazepines might be developed for clinical use as analeptics. 3. Microinjection of a BZ into the dorsal raphe nucleus acutely increases wakefulness, while administration into the medial preoptic area of the hypothalamus enhances sleep maintenance.

Animals↗
PubMed1990

Effects of buspirone on sleep and respiration.

Drugs used in the treatment of anxiety are frequently sedating and tend to be respiratory depressants. Buspirone, a nonbenzodiazepine anxiolytic agent, has little reported sedative effect. It has been shown to be a respiratory stimulant in an anesthetized, glomectomized cat model. In this study, we examined the effects of two intraperitoneal single doses (10 and 20 mg/kg) of buspirone on sleep and respiration in unanesthetized, intact, freely moving rats. Buspirone increased sleep latency (p less than 0.0001) and decreased total sleep (p less than 0.02) through reductions in both non-REM and REM sleep. Respiratory rate (p less than 0.0003) and ventilation (p less than 0.004) were significantly increased for 4 h after drug injection. The effects on respiration were independent of those on sleep; stimulation was evident in both waking and non-REM sleep. This study suggests that buspirone, in addition to being free of sedating and respiratory depressant side effects when prescribed for anxiety in humans, may be a respiratory stimulant whose effects persist in sleep.

Animals↗
PubMed1990

Clinical neuropharmacology of sleep.

Sleep affects, and is in turn affected by, cardiovascular, thermal, respiratory, endocrine, circadian, and sensory processes. Integrative areas of the basal forebrain play a crucial role, as does interaction with cholinergic and aminergic areas of the brain stem. AD, which affects a wide range of structures and functions, alters sleep in a manner distinguishable from depressive pseudodementia and may involve changes in autonomic function. Sleep apnea occurs with a high incidence in patients with AD, and the possibility should be explored that treating sleep apnea might be beneficial to their cognitive and affective status. Long-acting hypnotics can adversely affect daytime functioning. This might occur because of either direct effects on structures mediating sleep and cognition or, alternatively, exacerbation of sleep-related respiratory dysfunction. Studies of the benzodiazepine receptor complex may lead to the development of new drugs to aid sleep and wakefulness.

Alzheimer Disease↗
PubMed1990

Melatonin administration in insomnia.

Ten patients with persistent insomnia were randomized in a double-blind design and the effects of 1-mg and 5-mg oral dosages of melatonin on the electroencephalogram-recorded sleep were examined. Subjects showed no changes in either the onset or duration of sleep, nor any effect on mood or alertness the following day. A significant increase in rapid-eye-movement (REM) latency was noted at the 1-mg dose, though no other parameter of REM sleep was affected. The patients reported less sleep on both melatonin conditions. Despite this perception of decrease, overall subjective quality was reported to be improved.

Adult↗
PubMed1990

Effects of hemodialysis on sleep apnea syndrome in end-stage renal disease.

A high prevalence of sleep apnea syndrome has been reported in previous studies of patients with chronic renal failure. The possible effects of chronic hemodialysis on the magnitude and severity of sleep apnea have not yet been clarified. The present study was undertaken to understand this relationship, by examining subjective and objective measures of sleep on nights following hemodialysis compared to those without hemodialysis. Significant sleep apnea was noted in 6 of 11 patients. The percentage of apnea time comprised of obstructive apneas increased significantly on the nights following hemodialysis. No significant differences occurred between these nights in the subjective or EEG measures of sleep, or in the total number of disordered breathing events or level of arterial oxygen desaturation. The association between end-stage renal disease (ESRD) and sleep apnea syndrome remains highly significant, but seems not to be acutely altered by conventional hemodialysis treatment.

Female↗
PubMed1989

Evidence for the presence of a benzodiazepine receptor binding substance in cerebrospinal fluid of a rabbit model of hepatic encephalopathy.

Based on the reversal of hepatic encephalopathy in animal models with administration of specific benzodiazepine receptor antagonists, it has been postulated that this syndrome may be mediated by an endogenous benzodiazepine-like compound. In this study using a radio-receptor assay, evidence for the existence of this substance has been demonstrated in cerebrospinal fluid but not sera of rabbits with hepatic encephalopathy due to galactosamine-induced hepature failure. Cerebrospinal fluid from rabbits with hepatic encephalopathy caused 36.1 +/- 5.03% displacement of 3H-Ro 15-1788 specific binding to cortical benzodiazepine receptors, compared to 11.7 +/- 0.76% in control animals (P less than 0.01). The benzodiazepine receptor binding activity has been shown to behave as a competitive inhibitor of radiolabeled benzodiazepine receptor binding. The finding of endogenous benzodiazepine binding activity affords a potential explanation for the amelioration of hepatic encephalopathy in this model with the administration of benzodiazepine receptor antagonists.

Aminocaproates↗
PubMed1989

Sleep apnea syndrome in chronic renal disease.

PURPOSE: We performed this study in order to expand on an earlier report indicating a high prevalence of the sleep apnea syndrome in male patients with end-stage renal disease treated with hemodialysis and to determine whether patients with chronic renal insufficiency (prior to the initiation of therapy for end-stage renal disease) and female patients with end-stage renal disease treated with hemodialysis were affected. PATIENTS AND METHODS: Polysomnography was performed in 26 male and female patients with chronic renal insufficiency and end-stage renal disease treated with hemodialysis who were not receiving testosterone. They included 22 whose histories were suggestive of sleep apnea ("symptomatic") and four whose histories were not ("asymptomatic"). RESULTS: Sixteen of the symptomatic (73 percent) and none of the asymptomatic patients were found to have clinically significant sleep apnea syndrome (p less than 0.02). Both female patients and patients with chronic renal insufficiency had sleep apnea. In nine of these 16 cases, the disorder was primarily of the obstructive type. CONCLUSION: These preliminary data raise the possibility of an association of chronic renal disease and the sleep apnea syndrome, and suggest that some of the daytime sleepiness and disturbed nocturnal sleep in such patients may be related to sleep apnea. They also indicate that questioning patients with chronic renal disease and symptoms suggestive of a sleep disorder is useful in determining who are at high risk for the sleep apnea syndrome. Further study is required to establish a causal relationship between chronic renal disease and the sleep apnea syndrome, and to determine the prevalence of the latter in patients with end-stage renal disease.

Adult↗