Sulfatide synthesis: inhibition by experimental allergic encephalomyelitis serum.

The rate of (35)S incorporation into cerebroside sulfate in cultures of embryo mouse spinal cord shows a rapid acceleration at the time of myelin formation. Exposure of cultures to dilute serum from rabbits with experimental allergic encephalomyelitis results in almost complete inhibition of sulfatide synthesis. Within 24 hours after replacement of inhibiting medium with normal medium there is an increase in sulfatide synthesis followed by myelination.

Cerebroside antibody inhibits sulfatide synthesis and myelination and demyelinates in cord tissue cultures.

Antiserum to cerebroside was prepared in rabbits by injection of cerebroside together with bovine serum albumin in complete Freund's adjuvant. When applied to cultures of embryo mouse spinal cord at explantation, this antiserum inhibited sulfatide synthesis and myelination; when applied to myelinated cultures it inhibited sulfatide synthesis and produced demyelination. Complement fixation assays also show antibody to cerebroside in serums from rabbits with experimental allergic encephalomyelitis induced by injection of whole white matter. Absorption of such serum with cerebroside abolishes the inhibiting and demyelinating activities.

Treatment modalities for narcolepsy.

Narcolepsy, a lifelong disorder, requires long-term management of symptoms. Interventions may be nonpharmacologic, such as lifestyle changes, and pharmacologic for relief of daytime sleepiness. Pharmacologic treatment of narcolepsy has depended on the use of CNS stimulants to increase wakefulness, vigilance, and performance. The medications considered effective in the treatment of narcolepsy include dextroamphetamine, pemoline, methylphenidate, methamphetamine, and modafinil; only methylphenidate hydrochloride and dextroamphetamine are approved for use in the United States. The currently available stimulants are associated with sympathomimetic side effects, limitations in efficacy, and negative effects on nighttime sleep. This has led to the development of alternative agents. Modafinil, a new wake-promoting agent, has been shown to be effective in reducing daytime sleepiness in patients with narcolepsy. The results of a United States 18-center randomized, placebo-controlled, 9-week trial of modafinil in the treatment of patients with narcolepsy has recently been reported. Patients receiving modafinil demonstrated significant improvement in all subjective and objective measures of sleepiness. Treatment with modafinil 200 mg and 400 mg daily significantly reduced mean scores on the Epworth Sleepiness Scale compared with baseline and placebo (p < 0.001) and significantly increased mean scores on the Maintenance of Wakefulness Test (p < 0.001) and the Multiple Sleep Latency Test (p < 0.001) compared with baseline and placebo. More improvement, as recorded on the Clinical Global Impression of Change scale, was seen in the modafinil group than in the placebo group at all time points (p < 0.001). Modafinil was well tolerated, with headache the only adverse event to occur significantly more often in the active treatment group (p < 0.05). These results suggest that modafinil is an important new therapeutic option for the treatment of narcolepsy.

Serological techniques for detection of antibody to galactocerebroside.

Two serological techniques were developed for the detection of antibody to galactocerebroside using liposomes as a carrier for the lipid hapten. One assay is a radioimmunoprecipitation test employing [3H] cholesterol as a marker in the galactocerebroside-liposomes. The other is a less sensitive but quick and easy galactocerebroside-liposome agglutination assay. Specificity is demonstrated by comparison of titers when other lipid haptens replace galactocerebroside in the liposomes, and when other anti-glycolipid antisera are reacted with galactocerebroside-liposomes.

Pediatricians and sleep disorders: training and practice.

OBJECTIVE: A series of studies were conducted to investigate pediatricians' training, knowledge, and practices regarding sleep and sleep disorders in children and adolescents. METHOD AND RESULTS: Study 1, a national survey of 156 pediatric residency programs, found that pediatricians receive a mean of 4.8 hours of instruction on sleep and sleep disorders, although the mode and median hours of instruction is 0 hours. In study 2, 88 pediatricians completing a questionnaire concerning general knowledge about sleep disorders in children and adolescents received a mean score of 71.8% (range, 40% to 93%). Pediatricians appear to know the most about developmental issues and sleep hygiene and the least about specific disorders such as narcolepsy and parasomnias. In the third study, 183 pediatricians were surveyed about their actual beliefs and practices regarding young children's sleep problems. Together, those surveyed reported that approximately 25% of their patients experience some type of sleep problem. Most pediatricians recommend behavioral interventions, although 14.8% of pediatricians report prescribing pharmacological treatments, and 48.9% inform parents that their child is likely to outgrow the problem. CONCLUSIONS: The results of these studies support the need for more education in sleep and sleep disorders in children and adolescents within medical schools, pediatric residency programs, and the practicing pediatric community.

Relationship of autonomic nervous system activity to daytime sleepiness and prior sleep.

Autonomic nervous system (ANS) measures have been used frequently as measures of activation or arousal. However, their relationship to standard measures of alertness--the Multiple Sleep Latency Test (MSLT) and Stanford Sleepiness Scale (SSS)--and to the quantity and quality of prior sleep has not been determined. In this study, the direct pupil light reflex (PLR) was measured with the MSLT and SSS to determine how ANS activity varies with daytime sleepiness and how all three measures were related to prior nocturnal sleep in a group of patients with obstructive sleep apnea. When the effects of age and time of day were partialed out, PLR data suggest that increased sleepiness as measured by MSLT is significantly correlated with increased parasympathetic activity (r = -0.60, p less than 0.01) and not with decreased sympathetic activity (r = -0.24, not significant). These partial correlations were significantly different (p less than 0.05). Increased sleepiness as measured by the SSS was significantly correlated with decreased sympathetic activity (r = -0.46, p less than 0.05) and not with increased parasympathetic activity (r = -0.00, not significant). These partial correlations were significantly different (p less than 0.02). In the group of sleep apnea patients, the PLR suggests that increased number of apneas and hypopneas (sleep fragmentation) was significantly correlated with both decreased sympathetic activity and increased parasympathetic activity. These findings suggest that ANS activity is related to daytime sleepiness and to the quality of prior sleep.

Treatment of narcolepsy with codeine.

The effectiveness of codeine as a treatment for the excessive daytime sleepiness of narcolepsy was studied in two experimental trials. In an open trial of codeine in five narcoleptic subjects, dramatic clinical improvement was reported. However, all-night polysomnography and maintenance of wakefulness tests before and after codeine showed no significant differences. A double-blind placebo-codeine trial was conducted in which eight narcoleptic subjects received codeine for 1 week and placebo for 1 week in a random order. During the week they kept a diary, and on the sixth evening and for 10 h following awakening on the seventh day they were monitored by radiotelemetry in the sleep laboratory for electroencephalogram, electro-oculogram, and electromyogram. The results were analyzed for sleep stages as well as four levels of wakefulness. The results showed no significant differences in any of the objective sleep or wakefulness parameters. However, the diaries showed significantly fewer naps during the week on codeine as compared with the placebo week. Eighteen of 27 narcoleptic patients treated with codeine report clinical improvement. Codeine consistently results in subjective clinical improvement. However, this is not reflected in the objective measures generally used to assess daytime sleepiness.

Full polysomnography in the home.

STUDY OBJECTIVES: To evaluate unattended full polysomnography (PSG) recorded in the home by the DigiTrace Home Sleep System (DHSS) and to assess the ability to acquire, store and analyze polysomnographic data using the DHSS compared to standard paper PSG. DESIGN: Part 1 used a prospective, cross-over design. Part 2 consisted of a prospective concurrent collection of polysomnographic data. SETTING: Sleep Disorders Center in a university medical center. PARTICIPANTS: All adult patients who required standard clinical PSG as part of their clinical evaluation, regardless of suspected diagnosis, except patients requiring video recording for abnormal behaviors. MEASUREMENTS AND RESULTS: The DHSS is a digital recording system with miniature preamplifiers and the capacity to record 18 channels of polysomnographic data, including 4 channels of EEG (C3-A2, C4-A1, C3-O1 and C4-O2), right and left EOG, two channels of chin EMG, ECG naso-oral airflow, respiratory effort (piezo crystal thoracic and abdominal belts and bilateral interacostal EMG), snore microphone, bilateral anterior tibialis EMG, and body-position sensor. In part 1,77 DHSS home recordings were evaluated. No recordings were lost due to equipment failure and each parameter was scorable in greater than 95% of all epochs. Most of the subjective assessments by questionnaire following each study revealed no difference between the two testing situations. However, patients reported more sleep time and a better overall test experience in the lab. Assessments of sleep quality and morning alertness compared to usual were rated higher in the lab. After completing both studies, more patients preferred the lab study (p < .01), mostly because of minor inconveniences and apprehension regarding acquisition of data during the home study. There was no difference in the assessment of which test most accurately represented their sleep. In Part 2, the DHSS recorded concurrently with paper PSG in the laboratory in 16 patients. The results show no significant differences for any parameter and strong positive correlations for all parameters. CONCLUSION: Using the DHSS, unattended full PSG can be performed in the home with reliable and high quality recordings. Full PSG can be extended to a larger patient population, because it is no longer limited by the number of beds, and there is a reduction in cost due to elimination of overnight staff and facility cost.

The indications for polysomnography and related procedures.

This paper is a review of the literature on the use of polysomnography in the diagnosis of sleep disorders in the adult. It is based on a search of MEDLINE from January 1966 through April 1996. It has been reviewed and approved by the Board of Directors of the American Sleep Disorders Association and provides the background for the accompanying ASDA Standards of Practice Committee's Parameters for the Practice of Sleep Medicine in North America. The diagnostic categories reviewed are: sleep-related breathing disorders; other respiratory disorders; narcolepsy; parasomnias and sleep-related epilepsy; restless legs syndrome and periodic limb movement disorders: insomnia; and circadian rhythm sleep disorders. Where appropriate, previously published practice parameters papers are cited and discussed. The relevant published peer-reviewed literature used as the basis for critical decisions was compiled into accompanying evidence tables and is analyzed in the text. In the section on the assessment of sleep apnea syndrome, options for estimating pretest probability to select high risk patients are also reviewed. Sleep-testing procedures other than standard polysomnography are also addressed (daytime polysomnography, split-night studies, oximetry, limited full respiratory recordings, and less-than-full respiratory recording) and treatment-related follow-up studies are discussed.

Periodic leg movements in sleep following treatment of obstructive sleep apnea with nasal continuous positive airway pressure.

Periodic leg movements in sleep are shown to be a common finding in patients with OSA and may become evident or increase in severity after treatment of the OSA with NCPAP. Periodic leg movements in sleep were measured during baseline polysomnography, a NCPAP treatment trial, and a repeat NCPAP recording in 33 patients treated with NCPAP for OSA. During baseline PSG, nine patients had five or more PLMS per hour of sleep (index), while 14 patients had a PLMSI of 5 or more during the NCPAP trial and the repeat NCPAP recording. Among those patients with a PLMSI of 5 or more during repeat NCPAP studies, the PLMSI showed a significant increase from baseline to initial NCPAP (16.9 +/- 25.3 vs 39.3 +/- 29.4; p less than 0.001) and from baseline to repeat NCPAP (16.9 +/- 25.3 vs 42.9 +/- 39.8; p less than 0.05). The number of PLMS associated with electroencephalographic arousal also increased significantly from baseline to initial NCPAP (4.3 +/- 7.4 vs 9.7 +/- 8.9; p less than 0.05) and from baseline to repeat NCPAP (4.3 +/- 7.4 vs 16.5 +/- 18.6; p less than 0.05). The 14 patients with a PLMSI of 5 or more on the repeat NCPAP had significantly more stage 1 sleep and less REM sleep than 19 patients with a PLMSI of less than 5. Bilateral anterior tibialis EMG must be measured during NCPAP recordings in order to recognize sleep disruption caused by PLMS.

Repetitive nocturnal arterial oxygen desaturation and silent myocardial ischemia in patients presenting for vascular surgery.

OBJECTIVE: To determine whether nocturnal respiratory abnormality (cyclic oxygen desaturation and tachycardia) is associated with nocturnal myocardial ischemia in older individuals with ischemic heart disease. DESIGN: Non-invasive monitoring on a single occasion. SETTING: Tertiary care referral hospital. PATIENTS: Thirty four consecutive older (68.5 +/- 6 yrs) patients referred for elective abdominal or carotid reconstructive vascular surgery. RESULTS: Seven patients (21%) had moderately severe nocturnal respiratory abnormality, defined by more than 50 dips in arterial oxygen saturation and increases in heart rate during the night. Two of these seven had clinical risk factors for ischemic heart disease and had nocturnal myocardial ischemia. Ten patients (29%) developed ischemia at some time during the study, of whom seven hand known ischemic heart disease, hypertension, and/or angina. Those with increased nocturnal ischemia showed very low frequency (1-2 cycles per minute) cyclic heart rate oscillations and repetitive nocturnal episodes of arterial oxygen desaturation, similar to patients with sleep apnea. CONCLUSION: Repetitive nocturnal cyclic arterial desaturation and cyclic increases in heart rate are associated with nocturnal myocardial ischemia in individuals with clinical risk factors for ischemic heart disease. Further investigation in a large patient sample utilizing non-invasive monitoring of saturation, heart rate, and blood pressure may provide definitive evidence regarding causation of some of the nocturnal myocardial ischemia occurring in older individuals with vascular disease.

Avoiding false positive findings in measuring nocturnal penile tumescence.

The measurement and interpretation of nocturnal penile tumescence (NPT) studies depend on appropriate measurement techniques, knowledge of the conditions during which NPT was recorded, and a lack of preconceived notions about the relationship of penile circumference to penile rigidity. This case report illustrates several of the most common problems in the measurement and interpretation of NPT that could result in a false positive finding.

Antiserum induced myelination inhibition in vitro without complement.

Exposure of neonatal rat cerebellum cultures to antiserum to whole spinal cord or galactocerebroside inhibited myelin formation regardless of whether guinea pig serum was added fresh or after heating to 56 degrees C for 1 h in order to achieve complete removal of hemolytic complement activity. Myelination followed removal of antisera from the culture media. This suggests that the inhibition of primary myelination by anti-CNS tissue antiserum occurs through some mechanism other than as the result of a cytotoxic reaction against oligodendrocytes mediated via the complement system.

Sleep disorders.

Advancements in sleep research have led to the development of new standards of what is normal sleep and arousal and new diagnostic tests for the detection of sleep disorders. Millions of adults have frequent or chronic complaints about the quality and quantity of their sleep. Sleep complaints increase with increasing age and are more common in women than in men and in women over 45 than in younger women. Sedative-hypnotic drugs are taken more frequently by women than men, and the incidence of use increases with increasing age. Studies of sleep and sleep disturbances during the perimenopausal period suggest that difficulty falling asleep and frequent nocturnal awakenings result from hormonal changes, vasomotor symptoms, and possibly psychologic factors. Other causes for sleep complaints in menopausal and postmenopausal women are occult sleep disorders, especially periodic leg movements in sleep and sleep apnea syndrome. Sleeping pills are inappropriate for most patients with sleep complaints. If sleep difficulties persist after a trial of good sleep hygiene, further evaluation at a sleep disorders center is indicated.

Effects of low-dose naloxone on subjective alertness and pupil diameter in normal and narcoleptic subjects.

Recent evidence suggests that endogenous opiates may be involved in the pathophysiology of narcolepsy. To test this theory, the effect of 0.8 mg naloxone hydrochloride on pupil size and subjective alertness was measured in normal and narcoleptic subjects. Naloxone resulted in significant pupillary constriction in the normal but not in the narcoleptic subjects. The extent of contraction of the pupil light reflex was reduced significantly in the narcoleptic but not in the normal subjects. There was no effect on subjective ratings of alertness on the Stanford Sleepiness Scale or the visual analogue scale in either group. The naloxone-related miosis in the normal group confirms that naloxone is not a pure opiate antagonist. The lack of naloxone-related miosis in the narcoleptics suggests that narcoleptic individuals do not respond to naloxone as do normal individuals. However, this difference can not be definitely attributed to the antagonism of endogenous opiates. The reduction of the extent of contraction of the light reflex suggests that naloxone caused an increase in supranuclear inhibition of parasympathetic pupil reflex activity. However, this finding may have resulted from mechanical limitations of a small pupil or technical limitations of the recording equipment. This study does not support previous reports that naloxone causes an increase in subjective alertness in narcoleptics.

What is normal sleep in the elderly?

Changes in the sleep and daytime alertness of the elderly are common and are secondary to a variety of causes. These changes cannot be attributed solely to the aging process. The role of occult sleep disorders in producing these changes in significant, and severe sleep disruption in the healthy elderly is almost always secondary to a sleep disorder such as sleep apnea. A number of precautions must be kept in mind when interpreting studies of sleep in the elderly.

Muscle enzymes in the diagnosis of ovine weaner nutritional myopathy.

The diagnostic performance of plasma tests for muscle enzymes was measured in sheep from flocks affected by clinical and sub-clinical nutritional myopathy. Parallel combinations of tests for creatine kinase (CK), alanine amino transferase (ALT), aspartate amino transferase (AST) and lactate dehydrogenase had higher diagnostic sensitivity than CK alone. The enzymes ALT and AST showed the highest correlation with the degree of muscle damage. A parallel combination of tests for plasma CK and ALT as well as tests for plasma alpha-tocopherol and red cell glutathione peroxidase are recommended for the diagnosis of nutritional myopathy and a decision on the appropriate treatment. The number of false negative results based on a diagnosis from the microscopic examination of single muscles was higher than for the parallel combination of tests. The number of false negatives was highest for the vastus intermedius and lowest for the tensor fascia lata. Diagnosis using a panel of blood tests has the advantages of overcoming problems of inadequate muscle sampling, a larger number of sheep in the flock can be tested and a more rapid diagnosis can be obtained.

Plasma indicators of muscle damage in a model of nutritional myopathy in weaner sheep.

Subclinical nutritional myopathy was induced in 5-month-old sheep by feeding them a diet low in vitamin E and selenium. Subsequently clinical myopathy was induced by dosing with protected polyunsaturated fatty acids. Plasma activities of creatine kinase (CK), pyruvate kinase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase and aldolase, enzymes of muscle origin, all remained above their reference ranges in clinically affected sheep, but fluctuated widely. Similar fluctuations occurred in subclinically affected animals, resulting in some activities being within the reference ranges and some above, at different times. Plasma malondialdehyde, an indicator of lipid peroxidation, proved of no diagnostic value. Terminal plasma CK activities were significantly correlated with microscopic damage in the vastus lateralis (VL), but not the vastus intermedius (VI) or the tensor fascia lata (TFL) muscles. AST was the most highly correlated with damage in VI and VL. In two clinically affected sheep successfully treated with an oral dose of alpha-tocopherol acetate all enzymes decreased steadily to within their reference ranges, at rates probably related to their plasma half-lives. These results suggest that measurement of plasma CK activity would be useful in monitoring recovery of treated sheep.