Biomedical subjects
E O Bixler
Publications and source records attributed to E O Bixler.
Next-day memory impairment with triazolam use.
The prevalence, rate, and degree of memory impairment for next-day activities during a short, intermittent course of bedtime doses of triazolam, temazepam, and placebo were assessed in a double-blind parallel-group study. 5 of the 6 subjects in the triazolam group reported at least one episode of next-day memory impairment/amnesia, with a total of 12 episodes being reported for the 30 subject-drug nights (a rate of 40%). In the temazepam group there were no such episodes of memory impairment. Immediate and delayed recall were also tested and related to whether active drug or placebo had been taken the night before. Impairment of delayed recall was significantly and several times greater than that in the temazepam or placebo groups. Next-day memory impairment/amnesia after a bedtime dose of triazolam tended to increase with continued or intermittent drug use. Cognitive impairments associated with triazolam probably represent a spectrum of organic brain dysfunction, with memory impairment/amnesia and confusion being the commonest, and milder manifestations and hallucinations and delusions the more severe and less common, features.
Preoperative insurance status influences postoperative complication rates for gastric bypass.
One hundred morbidly obese patients who had gastric bypass surgery were studied to determine how various demographic and medical variables affected complication rates, weight loss, and reduction in comorbidities associated with obesity. During the follow-up period (range: 12 to 59 months), 42 patients developed at least 1 complication. Twenty-three patients developed postoperative medical complications, 9 developed psychiatric complications, and 24 developed complications related to food ingestion. No significant relationships were observed between outcome and age, sex, age of obesity onset, or associated medical disorders. Striking differences in outcome were noted, however, when patients were contrasted according to their preoperative insurance status. Patients dependent on medical assistance, social security disability, or workman's compensation (publicly funded group) (n = 40) developed significantly more medical and psychiatric complications than did those (n = 60) who had private medical insurance (p less than 0.02). Despite the higher complication rate, both groups had the same average weight loss (44.9 +/- 15.3 kg for the publicly funded group versus 43.1 +/- 12.9 kg for those with private insurance) and similar reductions in percent excess weight (66.0 +/- 18.4% versus 75.7 +/- 23.0%) during the first postoperative year. All patients also had similar reductions in medication requirements for hypertension, diabetes, and degenerative joint disease. Additionally, 45% of the publicly funded insurance group who either received public welfare (n = 26) or disability benefits (n = 14) preoperatively were able to attain either full-time or part-time employment postoperatively which allowed them to decrease their level of support (58% and 21%, respectively). Forty-six percent of women in the private insurance group who were not working outside the home also began part-time or full-time employment postoperatively. All patients who were working preoperatively continued to work. These data suggest that although the risks associated with gastric bypass surgery are greater in patients dependent on public funding, these patients benefit significantly from the surgery.
Effects of lovastatin and pravastatin on sleep efficiency and sleep stages.
The effects on sleep of two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (40 mg lovastatin and 40 mg pravastatin) were evaluated in 12 normal subjects in a double-blind placebo-controlled sleep laboratory study. Subjects were randomly assigned to each of two parallel groups (lovastatin and pravastatin). Each parallel-group protocol consisted of 22 consecutive nights including 4 placebo-baseline nights, 2 weeks of drug administration, and 4 placebo-withdrawal nights. Lovastatin did not disturb sleep initially (nights 5 through 7) but, with continued administration (nights 16 through 18), it significantly and markedly increased wake time after sleep onset and stage 1 sleep compared with baseline. By contrast, pravastatin was not associated with sleep disturbance either initially or with continued use. Neither drug caused any sleep disturbance after withdrawal. Lovastatin's sleep disturbing effects with continued administration are attributed to its high degree of lipophilicity in contrast with the hydrophilicity of pravastatin.
Rebound insomnia after only brief and intermittent use of rapidly eliminated benzodiazepines.
In three parallel groups, brief and intermittent administration and withdrawal of triazolam, 0.5 mg, temazepam, 30 mg, and placebo were assessed in a 12-night sleep laboratory study of 18 subjects with insomnia. With this intermittent schedule both drugs improved sleep, with about one-third reduction in total wake time; this reduction was significant for temazepam but not for triazolam. Even though the periods of drug administration were quite brief, withdrawal of triazolam consistently produced rebound insomnia, with increases in total wake time above baseline of 61% and 51%, respectively, for the first night of each withdrawal period. With temazepam this effect was more variable, with total wake time increased only with the second withdrawal period (39%). Thus these findings indicate that even under conditions of brief, intermittent use and withdrawal, triazolam and, to a lesser degree, temazepam produce rebound insomnia after abrupt withdrawal, thereby predisposing to drug-taking behavior and increasing the potential for drug dependence.
Suicide in Alaska Natives, 1979-1984.
Alaska native suicide data were reviewed for every Alaska native suicide (N = 90) from death certificate data for the years 1979-1984 and compared to suicide statistics of age- and sex-matched groups of the entire U.S. population. The yearly suicide rate for Alaska natives was about twice that for the United States. Most of this difference was accounted for by dramatically and significantly greater rates for young, single, Alaska native men compared to white men in the U.S.; this was true for both the 15-24 and 25-34 age groups. With advancing age, suicide rates among Alaska natives decreased; the rates for the 35-44 and 45-54 male groups were still much greater, but not significantly so, than the rates for the comparable U.S. groups. After age 55, no suicides were reported for Alaska natives while U.S. white men had their highest suicide rates in the 55-64 and 65 and above groups. A number of social factors appear to have fueled the rise in suicide rates in young Alaska native men, including: economic growth, industrialization and changing lifestyles; prevalence of firearms; and a high rate of alcoholism.
Buspirone: sedative or stimulant effect?
OBJECTIVE: The primary objectives of this study were to evaluate the effects of initial and continued administration of buspirone on sleep induction and maintenance and sleep stage parameters, to determine the presence or absence of any drug-induced side effects, and to ascertain the presence or absence of sleep disturbances following abrupt withdrawal of the drug. METHOD: Six insomniac subjects who had chronic complaints of difficulty falling asleep and/or staying asleep and who were in good physical health, were not suffering from any major mental disorders, and had not used any medication for at least the last month participated in a 16-night sleep laboratory protocol. The protocol consisted of 4 placebo-baseline nights, 7 nights on which buspirone, 10 mg at bedtime, was administered, and 5 placebo-withdrawal nights. RESULTS: Wake time after sleep onset increased moderately during the first 3 nights of drug administration (there was a marked and significant increase on the first night) and increased by lesser degrees with continued drug administration. Overall, reports of side effects were infrequent. Following drug termination, there was a delayed and mild increase in sleep difficulty above baseline. CONCLUSIONS: These data not only confirm that buspirone lacks sedative effects but also suggest that the drug may have stimulant properties. Further, these findings suggest that buspirone has limited usefulness in anxious patients with concomitant sleep difficulties.
Variables associated with frequency of rumination in a boy with profound mental retardation.
The relationships between frequency of rumination in a boy with profound mental retardation and a variety of environmental, interpersonal, and temporal variables were investigated by collecting and analyzing data during all waking hours over a 4-week period. Low levels of rumination were associated with periods of special education programming (versus nonschool hours), individual attention (versus group activities and independent play), and time spent with caretakers who like the child (versus those who like him less). The findings also revealed a mealtime effect (decreasing rumination as time elapsed following meals) and a time of day effect (increasing rumination as the day progressed). Directions for future research and possible implications for the environmental management of rumination are discussed.
Morphology of the uvula in obstructive sleep apnea.
Alterations in pharyngeal structure and function are considered fundamental in the pathogenesis of obstructive sleep apnea (OSA). However, little is known about morphologic features of the pharynx in patients with OSA. We therefore studied the tissue composition of the uvula (midsagittal section) in patients with OSA, using a quantitative, morphometric point-counting technique. Uvula tissue was obtained by uvulopalatopharyngoplasty (UPPP) in 33 patients (mean number of apneas per hour of sleep = 32.7 +/- 5.2) and by autopsy in 22 normal subjects not known to have OSA. All statistical comparisons were controlled for differences caused by age and body mass index. Patients with OSA had a significantly greater percentage of muscle in the uvula (18.1 +/- 1.9% versus 9.3 +/- 2.1%, p = 0.02) than did normal subjects. A significant difference in fat content was also found (9.5 +/- 1.4% in patients versus 4.0 +/- 1.0% in normal subjects, p less than 0.02). These differences between patients with OSA and control subjects could not be accounted for by anthropometric or sex differences. The percentage of uvula fat tissue was significantly related to the frequency of apneas and hypopneas in sleep (r = 0.43, p less than 0.01). Uvula morphology in 6 nonapneic snorers undergoing UPPP was similar to that of patients with OSA. We conclude that the uvula in patients with OSA contains more muscle and fat than the uvula in control subjects, possibly contributing to pharyngeal narrowing in OSA.
Effects of nadolol on blood pressure, sleep efficiency, and sleep stages.
The effects of nadolol (20 and 80 mg) on blood pressure and sleep parameters were assessed in six patients with mild hypertension. A 32-night experimental protocol in the sleep laboratory was instituted consisting of four placebo-baseline nights followed by 4 weeks of drug administration. Both doses of nadolol had a clear-cut and consistent lowering effect on blood pressure throughout the night and during the day, with a greater reduction noted with the 80 mg dose. In fact, blood pressure values were reduced to normotensive levels. Neither dose had a disrupting effect on sleep, whereas the 80 mg dose improved sleep efficiency and also had a rapid eye movement-enhancing effect. This absence of sleep-disrupting effects is attributed to nadolol's low level of lipophilicity and lack of intrinsic sympathomimetic activity. The clinical significance of the lack of sleep disruption and possible improvement of sleep with nadolol is discussed in light of the well-recognized sleep disturbances produced by other beta-blockers.
Nocturnal sleep and blood pressure in essential hypertension.
Blood pressure and sleep-wakefulness patterns were monitored in the sleep laboratory over four consecutive nights in six patients with mild hypertension and six age- and sex-matched controls. In both hypertensives and normals, blood pressure levels decreased during sleep compared with presleep levels by 16.6 and 8.4%, respectively; levels for hypertensives, however, remained significantly above those for the normals. The nocturnal drop in blood pressure for both groups appeared to be related primarily to the general state of sleep rather than to any specific sleep stage. Nocturnal patterns of sleep stages and sleep cycling were almost identical for the two groups. Nocturnal blood pressure fluctuation was correlated positively with the distribution of nocturnal wakefulness in hypertensives but not in normotensives. This suggests that with hypertension there is some diminution of the dampening effect of sleep itself upon blood pressure which normally carries over into periods of nocturnal wakefulness. This alteration in patients with mild hypertension may reflect a decrease in the sensitivity of the baroreceptor reflex or some other pathophysiological process.
Diazepam: effects on sleep and withdrawal phenomena.
Diazepam 10 mg was evaluated in a sleep laboratory study of six insomniac subjects. The protocol, which lasted for 18 consecutive nights, including four placebo-baseline, seven drug, and seven placebo-withdrawal nights, allowed for assessment of initial and short-term drug effects, side effects, and any withdrawal effects. With initial drug use, there was a significant improvement in sleep. Further, there was little evidence of tolerance developing at the end of the 1-week drug administration period. During drug administration there was a mild degree of daytime sedation reported. After abrupt termination of diazepam, there was a moderate degree of sleep difficulty on the sixth withdrawal night when total wake time was increased by 34% above baseline (not significant). On other nights, mild withdrawal changes were noted. These findings for the short-term administration and withdrawal of diazepam contrast with those for rapidly eliminated benzodiazepine drugs. The latter are characterized by a rapid development of tolerance and more frequent and intense withdrawal sleep disturbances.
Alprazolam: effects on sleep and withdrawal phenomena.
Alprazolam was evaluated in chronic insomniacs in a 1-mg bedtime dose. The 16-night sleep laboratory protocol included four placebo-baseline nights followed by seven nights of drug administration and five placebo-withdrawal nights. On the first three drug nights (nights 5 to 7), the drug was highly effective in inducing and maintaining sleep with this short-term use. By the end of the one week of administration (nights 9 to 11), however, the drug had lost about 40% of its efficacy. During drug use, one subject reported some difficulty in controlling expression of inappropriate emotions when interacting with others, which suggested the presence of disinhibition. On the third night following drug termination, there was a significant increase in sleep difficulty above baseline levels (rebound insomnia). This worsening was of comparable magnitude to the peak improvement of sleep with drug administration. Thus, the clinical utility of alprazolam when administered to insomniac patients appears to be limited because of a relatively rapid development of tolerance and possible disinhibitory reactions during drug use and the occurrence of rebound insomnia following withdrawal.
Normal sleep: patterns and mechanisms.
In the last three decades, research in the sleep laboratory has decisively contributed to a much deeper knowledge of sleep physiologic and pathologic states. Parallel to clinical research related to sleep disorders, multifaceted basic research has greatly contributed to a better understanding of the mechanisms underlying sleep and wakefulness. This basic research in the realm of the neurosciences integrates data derived from the application of various methodologic approaches. Currently, the prevailing concepts about sleep mechanisms generally favor the idea of a dynamic interaction among systems rather than that of a unidimensional explanation for sleep generation. Examples of these integrative concepts in current sleep research are the revised model of reciprocal interaction for the control of REM sleep and the two-process model comprising the seemingly incompatible homeostatic and circadian sleep mechanisms. In sleep disorders medicine, the prevailing approach is also integrative: findings from the sleep laboratory are considered in conjunction with those from clinical experience in understanding the nature of sleep disorders. Applying this integrative model, physicians in sleep disorders medicine are able to manage patients with sleep disorders comprehensively. Based on an understanding of sleep physiology, clinicians can make the diagnosis of most sleep disorders in the office setting.
Uvulopalatopharyngoplasty as a treatment of obstructive sleep apnea precipitated by uvular prolapse.
Two patients are discussed in whom obstructive sleep apnea was precipitated by uvular prolapse into the larynx and successfully treated by uvulopalatopharyngoplasty. Although tracheostomy has been the definitive treatment for obstructive sleep apnea, uvulopalatopharyngoplasty has also been used as an alternative surgical procedure. However, indications for its successful use have not been clearly defined. Our experience illustrates that the surgical approach to obstructive sleep apnea is dependent on a thorough diagnostic evaluation that includes a sleep history, head and neck examination, hypnopolygraphic recording and, if indicated, nocturnal fiberoptic endoscopy.
Narcolepsy/cataplexy. IV: Diagnostic value of daytime nap recordings.
Sleep and wakefulness patterns in daytime naps of 50 patients with narcolepsy/cataplexy were compared with those of 50 controls. Each subject was monitored polygraphically during 2 one-hour nap periods. A sleep-onset REM period in either of the 2 daytime naps was observed to have a higher diagnostic sensitivity (78%) than an abnormally shortened sleep latency (68%). However, the specificities of a sleep-onset REM period (88%) or abnormally shortened sleep latency (90%) were quite similar. When the occurrence of either a sleep-onset REM period or a shortened sleep latency was evaluated in either of the two naps, the overall sensitivity was increased to 84% while the specificity was decreased only to 80%. The limitations of and indications for the use of testing for sleep and REM latencies in the diagnosis of narcolepsy in clinical practice are discussed.
Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system.
The rates of reported adverse drug reactions involving the central nervous system were compared among patients taking any of three benzodiazepine hypnotics: flurazepam, temazepam, and triazolam. These rates, based upon data collected through the spontaneous reporting system of the Food and Drug Administration, were controlled for the number and size of new prescriptions for each drug. In general, triazolam had much higher overall rates than did the other two drugs. Hyperexcitability and withdrawal effects were greatest for triazolam and least for flurazepam. Amnesia was reported almost exclusively with triazolam. Rates for other cognitive as well as affective and other behavioral effects were also much greater for triazolam and about equal for the other two drugs. Finally, daytime sedation was reported slightly more for flurazepam than triazolam and least for temazepam which was also reported most frequently as lacking hypnotic effect.