Sleep and breathing in patients with the Prader-Willi syndrome.

The Prader-Willi syndrome is characterized by infantile hypotonia, early childhood obesity, mental deficiency, short stature, small hands and feet, and hypogonadism. Many patients also have hypersomnolence, experience daytime hypoventilation, and subsequently die prematurely of cardiorespiratory failure. Hypersomnolence and daytime hypoventilation are also common occurrences in the sleep apnea syndrome. For a better understanding of the relationship of sleep to the features of the Prader-Willi syndrome, we retrospectively reviewed five patients (two adults, one adolescent, and two children) with this syndrome who underwent polysomnography. All patients were obese; they had hypersomnolence and daytime hypoxemia, and they nored. In all patients, the apnea plus hypopnea index was less than 10 episodes per hour of sleep. During rapid eye movement sleep, nonapneic reductions in oxyhemoglobin saturation were detected in one adult and in one child. Despite the presence of morbid obesity and a history of snoring, patients with Prader-Willi syndrome seem to have only mild sleep-disordered breathing.

Effect of pramipexole in treatment of resistant restless legs syndrome.

OBJECTIVE: To report the results of an open-label trial with a dopaminergic agent, pramipexole, in patients with treatment-resistant restless legs syndrome (RLS). MATERIAL AND METHODS: We studied the response to pramipexole in a consecutive series of 16 patients with symptomatic RLS who had previously experienced failure with other dopaminergic therapies. Patients assessed their posttreatment change in symptoms of RLS on a visual analog scale and indicated drug-related side effects with use of a checklist. RESULTS: With a mean dose of pramipexole of 0.3 mg, most patients reported clinically significant improvement. From 2 to 3 months after initiation of pramipexole therapy, nocturnal leg restlessness, involuntary leg movements, and insomnia had decreased in 12, 10, and 11 patients, respectively. The most frequent adverse effects were fatigue and stiffness, which occurred in a third of the patients. Overall, the drug was well tolerated. CONCLUSION: On the basis of these findings, we propose that pramipexole, a D2 subgroup receptor agonist, is an effective agent for treatment of RLS.

Narcolepsy update.

Narcolepsy, a disorder of excessive daytime sleepiness that affects more than 125,000 people in the United States, is technically defined as a daytime mean sleep latency (time elapsed before falling asleep) of less than 5 minutes in conjunction with verification of rapid eye movement sleep in at least two of five daytime nap periods. Cataplexy, hypnagogic hallucinations, and sleep paralysis are frequently associated with narcolepsy. Currently, overnight polysomnography and multiple sleep latency testing in a sleep disorders laboratory are used to diagnose narcolepsy. Standard pharmacologic therapy consists of the judicious use of stimulants to improve alertness and the administration of tricyclic and other antidepressant drugs to suppress cataplexy. In addition, good sleep hygiene (a regular sleep-wake schedule, an adequate amount of sleep at night, and scheduled daytime naps) is essential for optimal management of this disorder. Patient and family education about narcolepsy and its treatment is also important. Even with use of the best available treatment regimens, many patients with narcolepsy have substantial vocational and social impairments.

Obstructive sleep apnea manifesting as suspected angina: report of three cases.

OBJECTIVE: To describe three cases of obstructive sleep apnea that resembled coronary artery disease and to suggest features that might distinguish these two syndromes. DESIGN: We present three detailed case reports of patients with severe obstructive sleep apnea and discuss similar cases from the literature. MATERIAL AND METHODS: Two obese women and one obese man with previously undiagnosed obstructive sleep apnea had chest discomfort, episodic dyspnea, and palpitations, most prominent at night. All three patients had multiple cardiac risk factors and had previously undergone cardiac evaluations, including at least two prior cardiac catheterizations each. Repeated cardiac catheterization revealed less coronary occlusive disease than expected on the basis of the symptoms in all three patients and a small atrial septal defect in one patient. When reassessed, the medical histories suggested obstructive sleep apnea. RESULTS: Overnight polysomnography documented the presence of severe sleep apnea; the three patients had mean values of 56 disordered breathing events per hour and 44% minimal oxygen saturation. Although bi-level or continuous positive airway pressure yielded initial improvement, all patients had difficulty with routine use of this therapy after 1 1/2 years of follow-up. CONCLUSION: The initial manifestations of severe obstructive sleep apnea may simulate angina, suggest arrhythmia, or mimic heart failure. Failure to inquire about snoring and daytime somnolence in patients with chest pain may prevent the identification of clinically significant disordered breathing during sleep.

Corticosteroid abuse--an unusual manifestation of drug dependence.

A depressed 44-year-old man presented with a 2 1/2-year history of use of a synthetic glucocorticoid (prednisone) as the only psychoactive drug. The pattern of use strongly suggested drug dependence; secondary Cushing's syndrome was noted. We call attention to the potential abuse of neuroendocrine agents and, more specifically, corticosteroid preparations.

Sleep disorders in psychiatric practice.

Sleep disorders medicine and psychiatry interface in numerous ways. Most psychiatric patients have a complaint about sleep, and regardless of the theoretical orientation of a psychiatrist, understanding of a patient's sleep function is an important part of assessment. The success or failure of treatment will be strongly influenced by the effect of that treatment on the patient's sleep disorder. The psychiatrist can provide expertise in treating patients with primary sleep disorders, offering pharmacologic consultations, and recommending psychotherapy or behavioral management. Conversely, a knowledge of primary sleep disorders should make the psychiatrist a more effective practitioner.

Theophylline effect on sleep in normal subjects.

In an effort to isolate the effect of theophylline on sleep from the effect of asthma, we examined the impact of oral theophylline on sleep quality in normal, nonasthmatic subjects. Ten healthy, nonsmoking, male subjects ranging in age from 23 to 35 were studied. The subjects were randomly divided into two groups and studied in a double-blinded, crossover designed protocol. Each group underwent two consecutive nights in the sleep laboratory. Group one received four doses of 300 mg of sustained-release theophylline at 12-h intervals prior to the study night. Group two received a placebo. After 14 days, the patients crossed over to the other group, and the procotcol was repeated. The mean serum theophylline level on the morning following the study night was 7.85 +/- SD 2.12 micrograms/ml, with a range of 5.1 to 12.1 microns/ml. The analysis of variance for a crossover design showed no order effect. The analysis for drug effect showed that theophylline administration resulted in a statistically significant adverse effect on arousals per sleep hour (19.3 vs 15.9 for placebo, p = .006) and total sleep time (370.9 min vs 399.45 min for placebo, p = .015). Comparing the sum of ranks data, theophylline was found to have a significant adverse effect on sleep quality (p = .036). We conclude that low doses of oral theophylline result in a significant disturbance in sleep quality in normal nonasthmatic subjects.

High dose transdermal nicotine therapy for heavy smokers: safety, tolerability and measurement of nicotine and cotinine levels.

Transdermal nicotine has been shown to relieve nicotine withdrawal and to double smoking cessation rates compared to placebo in clinical trials. A 21 or 22 mg/day dose provides a steady state serum nicotine that is less than obtained from smoking. Limited information is available about higher nicotine patch doses. To define better the optimal dosing of nicotine patch therapy, we undertook an open-label study to determine the safety and tolerability of 44 mg/day dose for smoking cessation in subjects smoking > or = 20 cigarettes per day. Forty smokers received 44 mg/day of transdermal nicotine for 4 weeks followed by 4 weeks of 22 mg/day. Of the 40 subjects enrolled, 38 (95%) completed the 4 weeks of 44 mg patch therapy and 36 (90%) completed the entire 8 weeks of patch therapy. Non-smokers at week 4 had a mean serum nicotine level of 23.4 +/- 11.7 ng/ml and cotinine of 152.2 +/- 87.3 ng/ml. Percent replacement was calculated by dividing the steady state level at week 4 by the baseline level while the subjects were smoking their usual number of cigarettes. Percent nicotine replacement for non-smokers at week 4 (while on 44 mg nicotine patch) averaged 158% +/- 108.4, and for cotinine was 112.0 +/- 73.8. For nicotine, 33% of non-smokers at week 4 had < or = 100% nicotine replacement and for cotinine 63% < or = 100% replacement. Biochemically confirmed point prevalence smoking cessation rates were 65% and 55% at weeks 4 and 8 of patch therapy, respectively, and self-reported smoking cessation at 3 months was 50%. The most common effect was skin irritation at the patch site. A single subject was admitted for myocardial infarction following step-down from 44 to 22 mg of replacement nicotine. The subject was not smoking and the adverse event was deemed to be not related to the patch therapy. Sleep complaints were reported in 33% of subjects during the 44 mg phase. Other complaints were infrequent. We conclude that 44 mg per 24-h nicotine patch therapy in heavy smokers is safe, tolerable, and without significant adverse events.

Hallucinogens antagonize histamine H1 receptors of cultured mouse neuroblastoma cells.

Hallucinogens were competitive antagonists of histamine at the H1-receptor of cultured mouse neuroblastoma cells. Their rank order of potency at this receptor was similar to that for their potency at eliciting subjective effects in vivo. Comparison with studies of other receptors, however, suggests that no single model of drug--receptor interaction adequately accounts for the known subjective effects of these compounds.

Alcoholism in a coronary care unit population.

To estimate prospectively the concordance between diagnoses of alcoholism by a physician and by use of a questionnaire-type screening test in patients in a coronary care unit, we studied 608 patients admitted to a coronary care unit in a 5 1/2-month period. The results from the Self-Administered Alcoholism Screening Test (SAAST) were compared with the diagnoses by physicians recorded in the medical records for the same patients. A strong association (P < 0.001) existed between the clinicians' identification of an alcohol problem and the SAAST scores indicative of such a problem. However, 23 (4.2%) patients were identified as alcoholics by the SAAST but not by clinicians, and 16 (2.9%) patients were identified as alcoholics by clinicians but not by the SAAST. The SAAST was well accepted in this coronary care unit and can complement and extend the clinicians' impression, although each approach may identify some patients that the other will miss. Routine use of the SAAST in the coronary care unit or other hospital settings is feasible and, with appropriate clinician assessment and physician involvement, should yield more complete evaluation and case finding for alcoholism.

Prevalence of glaucoma in patients with obstructive sleep apnoea--a cross-sectional case-series.

AIM: To determine the prevalence of glaucoma in patients with obstructive sleep apnoea. DESIGN: Cross-sectional case series. PARTICIPANTS: One hundred patients with moderate to severe obstructive sleep apnoea. TESTING: Within 48 h of the polysomnographic diagnosis of obstructive sleep apnoea, patients underwent the following tests: intraocular pressure, gonioscopy, automated perimetry, stereoscopic biomicroscopy, and fundascopic assessment for the presence of glaucomatous optic nerve changes. MAIN OUTCOME MEASURES: The prevalence of glaucoma in patients with obstructive sleep apnoea and the associations between patient characteristics and both glaucoma and intraocular pressure. RESULTS: Glaucoma was diagnosed in 27 of 100 patients yielding an estimated prevalence of 27% (95% CI 19-37%). The presence of glaucoma did not correlate with sex, body mass index (BMI), or AHI, but did appear to be associated with age (P=0.014). There was no evidence of a relationship between intraocular pressure and either the apnoea plus hypopnoea index or age. CONCLUSION: The prevalence of glaucoma in patients with obstructive sleep apnoea is an estimated 27%. Sex, age, body mass index or apnoea plus hypopnoea index are not factors influencing the presence of glaucoma in this population of patients.

Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up. One-year outcome and percentage of nicotine replacement.

OBJECTIVE: To determine the efficacy of a 22-mg nicotine patch combined with the National Cancer Institute program for physician advice and nurse follow-up in providing withdrawal symptom relief, 1-year smoking cessation outcome, and percentage of nicotine replacement. DESIGN: Randomized, double-blind, placebo-controlled trial. SUBJECTS: Two-hundred forty healthy volunteers who were smoking at least 20 cigarettes per day. INTERVENTIONS: Based on the National Cancer Institute program, subjects received smoking cessation advice from a physician. Follow-up and relapse prevention were provided by a study nurse during individual counseling sessions. Subjects were randomly assigned to 8 weeks of a 22-mg nicotine or placebo patch. MAIN OUTCOME MEASURES: Abstinence from smoking was verified by expired air carbon monoxide levels. Withdrawal symptoms were recorded during patch therapy, and the percentage of nicotine replacement was calculated by dividing serum nicotine and cotinine levels at week 8 of patch therapy by levels obtained while smoking. RESULTS: Higher smoking cessation rates were observed in the active nicotine patch group at 8 weeks (46.7% vs 20%) (P < .001) and at 1 year (27.5% vs 14.2%) (P = .011). Higher smoking cessation rates were also observed in subjects assigned to the active patch who had lower serum levels of nicotine and cotinine at baseline, and withdrawal symptom relief was better in the active patch group compared with placebo. CONCLUSIONS: Clinically significant smoking cessation can be achieved using nicotine patch therapy combined with physician intervention, nurse counseling, follow-up, and relapse prevention. Smokers with lower baseline nicotine and cotinine levels had better cessation rates, which provides indirect evidence that they had more adequate nicotine replacement with this fixed dose of transdermal nicotine than those smokers with higher baseline levels.