Compensatory sleep responses to wakefulness induced by the dopamine autoreceptor antagonist (-)DS121

The effect of the dopamine autoreceptor antagonist (-)DS121 on wakefulness, locomotor activity, body temperature and subsequent compensatory sleep responses was examined in the rat. Animals entrained to a light-dark cycle were treated at 5 h after lights-on (CT-5) with 0.5, 1, 5 or 10 mg/kg i.p. (-)DS121 or methylcellulose vehicle. An additional group received 5 mg/kg i.p. (-)DS121 or vehicle 6 h after lights-off (CT-18). At CT-5, (-)DS121 dose-dependently increased wakefulness, locomotor activity and body temperature, and decreased both non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM) during the first 4 h post-treatment relative to vehicle controls. REM interference lasted up to 3 h longer than NREM. Low doses of (-)DS121 (0.5 and 1 mg/kg) produced relatively little waking that was not followed by significant compensatory sleep responses. In contrast, higher doses (5 and 10 mg/kg) produced compensatory hypersomnolence (robust increases in NREM immediately after the primary waking effect) that was proportional to the duration of drug-induced wakefulness. NREM recovery 24 h post-treatment was the same for the 5 mg/kg (65.4 +/- 9.9 min) and 10 mg/kg (64.8 +/- 9.3 min) doses, but was not proportional to prior wake duration. NREM displaced by drug-induced wakefulness was recovered completely by 24 h post-treatment at the 5 mg/kg dose, but only 63.5% recovered at 10 mg/kg. In contrast, equivalent wakefulness produced by sleep deprivation yielded 100% NREM recovery. At CT-18, (-)DS121 (5 mg/kg) increased wakefulness without disproportionately increasing locomotor activity, and was compensated fully by 24 h post-treatment. These data show that (-)DS121 dose-dependently increases wakefulness, which is followed by hypersomnolence that is proportional to drug-induced wake-promoting efficacy.     

Sleep and quantitative EEG in patients with progressive supranuclear palsy

Sleep architecture and quantitative EEG from wakefulness and REM sleep were studied in six patients (mean age, 70.5 years) with progressive supranuclear palsy (PSP) and compared with that of six control subjects (mean age, 69.8 years). Particular attention was given to quantifying REM sleep variables because of the known PSP-associated degeneration of the pedunculopontine tegmentum (PPT)--a critical structure in REM sleep generation. Patients with PSP had a shorter total sleep time, a lower sleep efficiency, a drastic reduction in sleep spindles, an atonic slow-wave sleep, and a lower percentage of REM sleep. The lower percentage of REM sleep was the result of both a reduction in the number of REM periods and a reduction in mean period of duration. REM density was also reduced while REM efficiency, atonia, and phasic EMG were similar to control values. REM sleep findings are consistent with the known role of the PPT in REM sleep induction. A slowing of the awake EEG was found for the six frontal leads and for C4, P4, and T4 in PSP patients. The frontal EEG slowing found in wakefulness is in accord with imaging and neuropsychological studies showing impairment of the frontal lobes in these patients. REM sleep EEG was not significantly slower in any regions. Because all previous studies on PSP have relied on visual inspection of the EEG tracings, the present finding of EEG slowing in the frontal lobes (rather than in the temporal regions or diffusely) suggests that our quantitative EEG approach may be more useful in determining specific regions of impaired cortical activity.     

Chronic low-amplitude electrical stimulation of the laterodorsal tegmental nucleus of freely moving cats increases REM sleep

While cholinergic stimulation of the PRF evokes a REM-like state, electrical stimulation of LDT/PPT neurons has not been used to test the hypothesis of mesopontine cholinergic control of REM sleep. Adult cats were implanted for electrographic recording and with bipolar unilateral stimulating electrodes, either in the LDT or within the PRF (stimulation control). Baseline recordings of the normal sleep-wake cycle were carried out for 5 h. On the next day, continuous stimulation of the LDT or mPRF was carried out during the same time period (0.5 ms pulses, 1 microA, 8 Hz) and with post-stimulation recording for 3 h. A second baseline recording day followed with same protocol as the first baseline day. This 3-day sequence, separated by 3 days, was repeated three times in each of the three LDT and the three medial PRF cats. Five hours of chronic low-amplitude stimulation of the LDT induced a highly significant increase in total REM and in the duration of REM sleep bouts. Stimulation of the mPRF did not affect any of the behavioral states. This study, the first to our knowledge to use low-amplitude stimulation of LDT in freely moving cats, indicates the importance of mesopontine cholinergic neurons in REM sleep.     

Agonist regulation of beta-adrenergic receptors: immunoblotting and indirect immunofluorescence reveal agonist-induced lateral sequestration and loss of binding

Sleep and wakefulness were studied polygraphically in two adult male ferrets between the ages of 3 months and 2.5 years. Nine 24-hour recordings were obtained on different light/dark schedules, and one animal was also monitored for 3 days following administration of the serotonin synthesis inhibitor, parachlorophenylalanine. Stage scoring was accomplished utilizing criteria similar to those used in the cat. Certain modifications to the criteria were made to accommodate apparent differences in electrographic indicators of state. Mean daily percentages [+/- standard error of the mean (SEM)] for the major stages were: slow-wave sleep, 36.0 +/- 1.33; rapid eye movement (REM) sleep, 24.4 +/- 0.94; and wake, 39.4 +/- 1.17. Under laboratory conditions, ferrets spend over 60% of the time in sleep and 40.28% +/- 0.93% of total sleep time in REM sleep. The high amount of REM sleep is achieved by having a high number of REM sleep episodes rather than long REM periods. Sleep cycle length was computed in two ways: with long wake episodes removed, 16.7 +/- 0.4 minutes; and with all wake removed, 13.2 +/- 0.3 minutes. Sleep and waking indices in the ferret are compared to those in the cat and discussed with respect to predictions based on several constitutional variables. The high amount of REM sleep and the relative immaturity of the ferret at birth lends additional support for a functional role of REM sleep on ontogenetic development.     

Scalp recorded direct current brain potentials during human sleep

The direct current (DC) potential recorded from the scalp of awake humans has been considered a reflection of general changes in cortical excitability. This study examined DC potential shifts in humans during a night of continuous sleep. Standard polysomnographic recordings and skin temperature were measured simultaneously. Contrary to expectations, average DC potential level indicated higher negativity during nonrapid eye movement (NREM) sleep than REM sleep and wakefulness. Moreover, a dynamic regulation of the DC potential level was revealed in association with the NREM-REM sleep cycle comprising four successive phases: (i) a steep 'NREM-transition-negative shift' during the initial 10-15 min of the NREM sleep period; (ii) a more subtle 'NREM-positive slope' during the subsequent NREM sleep period; (iii) a steep 'REM-transition-positive shift' starting shortly prior to the REM sleep period, and (iv) a 'REM-negative slope', characterizing the remaining greater part of the REM sleep period. DC potential changes were only weakly related to changes in slow-wave activity (r2 < 0.18). The NREM-negative slope and REM-positive slope could reflect, respectively, gradually increasing and decreasing cortical excitability resulting from widespread changes in the depolarization of apical dendrites. In contrast, the NREM-transition-negative shift and the REM-transition-positive shift may reflect the progression and retrogression, respectively, of a long-lasting hyperpolarization in deeply lying neurons.     

The diurnal distribution of sleep propensity: experimental data about the interaction of the propensities for slow-wave sleep and REM sleep

The aim of the present study was to assess the diurnal variation of sleep propensity by evaluating the temporal distribution of sleep onset latency (SOL) and REM- and slow-wave sleep (SWS) parameters in systematically scheduled daytime naps for 12 young males. To reduce the effect of prior SWS on subsequent REM sleep, a double-nap technique was used, i.e. two adjacent naps A and B, which were separated by a 10-min break. Nap duration was adjusted in such a way that nap A allowed 30 min of sleep and nap B one complete NREM-REM cycle. EEG slow wave activity (SWA, power density from 0.5-4 Hz) was estimated from nap A and REM sleep parameters from nap B. The time span between 08.00 hours and 24.00 hours was covered by nine double-naps at 2 h intervals. The order of the nap sessions was systematically varied within and across subjects. For each subject, the time between successive double-nap recordings was at least three days. SOL was shortest in the time interval 12.00 hours to 16.00 hours and significantly longer between 20.00 hours and 24.00 hours. REM sleep duration and the percentage of sleep onset REM episodes decreased continuously from 08.00 hours to the interval 18.00-20.00 hours and increased thereafter, with a time course inversely related to the one of body temperature, which was also measured continuously. SWA showed a steady, threefold increase from 08.00 hours to 24.00 hours. The study offers new data on the diurnal variation of sleep propensity which seems to be a composite function of the drives for SWS and REM sleep.     

EEG slow waves and sleep spindles: windows on the sleeping brain

Slow waves and sleep spindles are prominent features of the EEG in non-REM sleep and some of the neurophysiological mechanisms underlying their genesis have been elucidated. In humans, slow-wave activity in non-REM sleep increases and EEG activity in the frequency range of sleep spindles decreases when wakefulness prior to sleep is varied from 2 to 40 h. The opposite changes are observed in the course of sleep, even when sleep is scheduled out of phase with the circadian rhythm of sleep propensity. Within non-REM sleep episodes the association between slow waves and sleep spindles is bi-phasic: both activities are correlated positively at the beginning and end of non-REM sleep episodes whereas in the middle part of non-REM sleep episodes high values of slow-wave activity coincide with low levels of spindle activity. An extension of wakefulness enhances the rise rate of slow-wave and spindle activity at the onset of sleep. Since macroscopic slow waves and sleep spindles both are dependent on hyperpolarization and synchronization of neurons in thalamo-cortical and cortical circuits, the sleep deprivation induced changes in these EEG activities may be related to reduced activating input to thalamo-cortical and cortical neurons, local facilitation of their hyperpolarization or facilitation of their synchronization. The precise regulation of slow-wave and spindle activity as a function of the duration and intensity of prior sleep and wakefulness demonstrates that these EEG oscillations are accurate indicators of non-REM-sleep homeostasis and suggests that they are fundamental to the sleeping brain.     

Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness

Both subjective and electroencephalographic arousal diminish as a function of the duration of prior wakefulness. Data reported here suggest that the major criteria for a neural sleep factor mediating the somnogenic effects of prolonged wakefulness are satisfied by adenosine, a neuromodulator whose extracellular concentration increases with brain metabolism and which, in vitro, inhibits basal forebrain cholinergic neurons. In vivo microdialysis measurements in freely behaving cats showed that adenosine extracellular concentrations in the basal forebrain cholinergic region increased during spontaneous wakefulness as contrasted with slow wave sleep; exhibited progressive increases during sustained, prolonged wakefulness; and declined slowly during recovery sleep. Furthermore, the sleep-wakefulness profile occurring after prolonged wakefulness was mimicked by increased extracellular adenosine induced by microdialysis perfusion of an adenosine transport inhibitor in the cholinergic basal forebrain but not by perfusion in a control noncholinergic region.     

Characterization of transition sleep episodes in baseline EEG recordings of adult rats

By scoring 5-s EEG epochs and calculating spectral power of consecutive EEG segments as short as 1-s, transition sleep (TS) episodes were identified in baseline recordings of adult rats. TS episodes were characterized by the abrupt appearance of theta and alpha waves within an ongoing period of slow-wave sleep (SS). They were followed by paradoxical sleep (PS) or, somewhat more frequently, by a period of wakefulness (W) that often led to an additional SS. Statistical values of the main variables of TS-->(W) and TS-->(PS) episodes are presented, together with comparable data concerning previous SS and following W or PS episodes. On the whole, TS episodes were more numerous than PS episodes, and less numerous than SS episodes. Their average duration was considerably shorter. As a consequence of the identification of TS and of brief W or PS epochs intervening within SS, the number of SS episodes was estimated to be considerably higher than previously assessed, and their average duration considerably shorter.     

Longtime administration of growth hormone-releasing hormone (GHRH) does not restore the reduced efficiency of GHRH on sleep endocrine activity in 2 old-aged subjects--a preliminary study

Aging results in a more shallow sleep accompanied by a blunted growth hormone (GH) secretion. In young male normal controls repetitive administration of GH-releasing hormone (GHRH) at the beginning of the night results in an increased secretion of GH, a blunting of cortisol and a stimulation of slow-wave sleep (SWS). In healthy elderly men and women, however, GHRH exerts only weak effects on sleep-endocrine activity. In a previous report continuous treatment of healthy elderly males by repetitive administration of GHRH (during 12 days administration with 100 micrograms GHRH i.v. at 9.00 h every second day, "priming") enhanced GHRH stimulated GH secretion at daytime markedly. We tested if priming with GHRH results in a more distinct modulation of the nocturnal hormone secretion and of the sleep EEG than acute administration of the peptide. Two elderly male controls spent first three consecutive nights in the sleep laboratory, the first of which served for adaptation to laboratory conditions. During the two other nights (at days 1 and 2) sleep EEG was recorded and blood was sampled for determining the secretion of GH, cortisol and ACTH. In one of the nights the subjects received 50 micrograms GHRH hourly between 22.00 h and 1.00 h (4 x 50 micrograms) or placebo. The next examination followed after the priming period at day 14 and the last was performed two weeks after treatment at day 28. After the baseline administration of 4 x 50 micrograms GHRH before priming no clear changes of sleep EEG towards improved sleep were detectable, whereas GH secretion was increased. After priming sleep period time and SWS time were lower compared to the baseline night with GHRH administration, whereas REM time duration increased. GHRH induced GH secretion was not enhanced after priming. ACTH secretion was markedly enhanced compared to baseline stimulation. We conclude that priming with GHRH has no sleep improving effect and does not change hormone secretion in elderly normal subjects. Hence in the elderly priming with GHRH is not capable to induce a rejuvenation of sleep endocrine activity.     

1997 Paul Ehrlich and Ludwig Darmstaedter Prize for the rediscovery of Helicobacter pylori to J. Robin Warren and Barry J. Marshall

The aim of this study was to: (i) test different instruments that focused on sleep, quality of life and personal adjustment in order to evaluate the usefulness of these instruments in a larger study; and (ii) to describe self perceptions of sleep and life situation by patients who had undergone coronary artery bypass grafting (CABG). A one-group pre-test repeated post-test design was used. Six men aged between 51 and 70 years were interviewed, and 24 h polysomnographic recordings were performed before and after the operation. The interviews indicated disturbed sleep and changes in behaviour and mental state immediately postoperatively. Postoperatively the polysomnographic recordings revealed a significant decrease in mean duration of sleep, mean percentage of stage 3-4 sleep and mean rapid eye movement (REM) sleep. One month after surgery the quality of life was improved, while moderate anxiety and sensation of incisional pain persisted. The measurements used in this pilot study provide valuable information into the understanding of altered sleep, quality of life and personal adjustment following CABG.     

The effect of unilateral destruction of the head of the caudate nucleus with kainic acid on the structure of the wakefulness-sleep cycle and the EEG in rats

The wakefulness-sleep cycle characteristics changes in Wistar line rats after unilateral lesions of the neuronal elements of the caudate nucleus head with kainic acid (at sparing the conducting ways going through this structure) were studied. It was shown that in 4 days after acid injection the share of the active wakefulness and light slow-wave sleep is significantly increased, whereas the percentage of the passive wakefulness, deep slow-wave stage, and paradoxal sleep (up to 80%) is reduced. The wakefulness-sleep cycle in rats is completely normalized on the 7th day after injection. The obtained data allow to consider the caudate nucleus as a modulator for wakefulness-sleep cycle, that is the structure involved in the motive activity regulation.     

Influence of sleep states on laryngeal and abdominal muscle response to upper airway occlusion in lambs

This study was aimed at describing abdominal and laryngeal muscle responses to upper airway occlusion (UAO) in early life and the effect of sleep states on these responses. Twelve nonsedated, 9-26-d-old lambs were studied. We simultaneously recorded 1) airflow (pneumotachograph + face mask); 2) sleep states (electrocorticogram and electrooculogram); 3) abdominal muscle (external obliquus) electromyogram (EMG); and 4) glottic constrictor (thyroarytenoid) and dilator (posterior cricoarytenoid and cricothyroid) muscle EMGs. The pneumotachograph was repeatedly occluded for 15-30 s in wakefulness and natural sleep. We analyzed 90 occlusions during wakefulness (11 lambs), 28 during non-rapid eye movement (nREM) sleep (six lambs), and 23 during rapid eye movement (REM) sleep (five lambs). A phasic expiratory external obliquus EMG was present during baseline and progressively increased throughout UAO in wakefulness and nREM sleep, but not in REM sleep. Phasic thyroarytenoid EMG progressively increased during inspiratory efforts throughout UAO in wakefulness and nREM sleep, paralleling the increase in glottic dilator (posterior cricoarytenoid and cricothyroid) EMG. In contrast, glottic muscle response to UAO in REM sleep was severely blunted or disorganized by frequent swallowing movements. We conclude that UAO triggers complex and coordinated laryngeal and abdominal muscle responses during wakefulness and nREM sleep in lambs; these responses are largely absent, however, in REM sleep. These unique results, together with the defective arousal response in REM sleep, suggest that vulnerability to airway occlusion could be increased during REM sleep in early life. Possible implications for understanding severe postnatal apneas are discussed.     

Differences in sleep variables, blood adenosine, and body temperature between hypothyroid and euthyroid rats before and after REM sleep deprivation

Sleep deprivation causes an increase in energy expenditure in animals. Thyroid gland function has been related to metabolic function, and this may be compromised in sleep manipulations. The objectives of the present study were the following: 1) to develop a model of hypothyroid rats by surgical removal of thyroid glands without extirpation of the parathyroid; 2) to observe the sleep architecture in euthyroid (Etx) and hypothyroid (Htx) rats, both before and after rapid eye movement (REM) sleep deprivation (96 hours); 3) to challenge both groups (i.e. Etx and Htx) with REM sleep deprivation (96 hours) and then evaluate the effects on temperature; and 4) to measure the levels of adenosine and thyroid hormones in blood. One-month-old Wistar male rats (weight 90-100 g) were studied. The thyroid gland was removed, and the parathyroid glands were reimplanted within the neck muscle (Htx) under halothane anesthesia. A sham-operated group was also included (Etx). Four months later, the animals were studied according to the following protocols. Protocol 1: Animals of both groups (i.e. Etx and Htx) were implanted for sleep recordings. After a baseline polysomnography, these animals were REM sleep deprived by the platform method (96 hours). Protocol 2. An intraperitoneal temperature transducer was placed into animals of both groups under deep halothane anesthesia. They were studied at baseline, during 96 hours of REM sleep deprivation, and on the rebound period. Protocol 3: Plasma thyroid hormones [T3, T4, and thyroid-stimulating hormone (TSH)] and plasma adenosine were determined in both groups. Results of protocol 1 indicated that the main difference observed in Htx rats during the baseline sleep was an increase in delta sleep (slow-wave sleep 2) and a reduction in waking time compared with Etx animals. REM sleep rebound after 96 hours of REM sleep deprivation was similar in both groups. In protocol 2, the main finding was that Htx animals had reduced body temperature. A significant difference in body temperature between Etx and Htx animals was found mainly during lights-on period. REM sleep deprivation in the Etx group produced an increase in body temperature. Htx animals showed the opposite effect, with a reduction in body temperature during and after REM sleep deprivation. In protocol 3, the main findings were that Htx animals exhibited a significant reduction in blood thyroid hormones (T3, T4), and that they also had high levels of plasma adenosine. REM sleep deprivation produces changes in temperature regulation. The increase in body temperature during REM sleep deprivation may require thyroid integrity. Absence of the thyroid gland does not seem to influence REM sleep recovery after its deprivation. The high plasma adenosine levels found in the Htx group may explain the increase in delta sleep in this group.     

Sleep electroencephalographic abnormalities in adolescent depressives: effects of scopolamine

In contrast to sleep studies of adult depressives that have consistently demonstrated abnormalities of sleep continuity, slow-wave sleep, and REM sleep, existing studies of depressed children and adolescents have been conflicting. Furthermore, only one study has explored the cholinergic regulation of sleep in early-onset depressives. In the present study, the electroencephalographic sleep of 20 adolescent outpatients with major depressive episodes and 13 normal control adolescents was obtained on two separate 2-night sessions, 1 night incorporating challenge with scopolamine. Depressed adolescents showed increased baseline phasic REM sleep measures, increased arousals, a trend toward reduced slow-wave sleep, and a greater difference in the change of first REM period density on the scopolamine night versus placebo night compared to controls. These findings support the continuity of some sleep abnormalities of depression into adolescence, and suggest that adolescent depression may be associated with alterations of cholinergic neurotransmission in some patients.     

Sleep bruxism is a disorder related to periodic arousals during sleep

There is evidence that sleep bruxism is an arousal-related phenomenon. In non-REM sleep, transient arousals recur at 20- to 40-second intervals and are organized according to a cyclic alternating pattern. Polysomnographic recordings from six subjects (two females and four males) affected by sleep bruxism (patients) and six healthy age-and gender-matched volunteers without complaints about sleep (controls) were analyzed to: (1) compare the sleep structure of bruxers with that of non-complaining subjects; and (2) investigate the relations between bruxism episodes and transient arousals. Patients and controls showed no significant differences in conventional sleep variables, but bruxers showed a significantly higher number of the transient arousals characterized by EEG desynchronization. Bruxism episodes were equally distributed between non-REM and REM sleep, but were more frequent in stages 1 and 2 (p < 0.0001) than in slow-wave sleep. The great majority of bruxism episodes detected in non-REM sleep (88%) were associated with the cyclic alternating pattern and always occurred during a transient arousal. Heart rate during the bruxism episodes (69.3+/-18.2) was significantly higher (p < 0.0001) than that during the pre-bruxing period (58.1+/-15.9). Almost 80% of all bruxism episodes were associated with jerks at the anterior tibial muscles. The framework of the cyclic alternating pattern offers a unified interpretation for sleep bruxism and arousal-related phenomena.     

Anticonvulsant activity of felbamate in amygdala kindling model of temporal lobe epilepsy in rats

PURPOSE: Previous studies have demonstrated that felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate) at nontoxic doses exerts potent anticonvulsant activity in a variety of animal epilepsy or seizure models. We further characterized the anticonvulsant activity of FBM by using the kindling model of temporal lobe epilepsy (TLE). METHODS: The experiments were performed in fully kindled rats. The anticonvulsant effect of FBM was assessed by determining seizure severity, afterdischarge (AD) duration and seizure duration either at the focal seizure threshold, or after suprathreshold stimulation. In addition, the neurological performance of kindled rats after FBM administration was evaluated in the open field and by the rotorod test. RESULTS: FBM at doses of 12.5-50 mg/kg, given intraperitoneally (i.p.) 60 min before testing, dose-dependently increased the AD threshold (ADT). The maximal effect was achieved after the highest dose tested and reached almost 600% of the control ADT. This dose of FBM significantly diminished other seizure parameters, e.g., seizure severity, seizure duration, and AD duration. When the rats were stimulated with suprathreshold current (500 microA) seizure severity was moderately but significantly reduced. No behavioral abnormalities were noted in kindled rats after administration of either of the doses. CONCLUSIONS: FBM potently increases the threshold for focal seizures and reduces seizure severity, seizure duration, and AD duration at doses that produce no adverse behavioral effects in amygdala-kindled rats. These data are thus compatible with clinical experience with FBM in TLE and substantiate that kindling is a good predictor of anticonvulsant activity against TLE.     

An evaluative study of the short-term effects of once-daily, sustained-release theophylline on sleep in nocturnal asthmatics

OBJECTIVE: To examine the effects of once-daily, sustained-release theophylline on sleep patterns in nocturnal asthmatics. DESIGN: Double-blind, randomised, cross-over, placebocontrolled trial over 22 days. Seven-day period to establish therapeutic levels of theophylline (11.8 +/- 3 mg/l); 8-day cross-over period of 4 days' placebo or theophylline; 7-day baseline period. Electrophysiological sleep patterns, overnight bronchoconstriction and arterial O2 saturation monitored on nights 7, 11 and 15. SETTING: Sleep Laboratory, Medical School, University of the Witwatersrand. PATIENTS: Twelve volunteers who met the criteria for asthma, had previously used theophylline, were clinically stable and had a history of nocturnal awakenings caused by asthma were enrolled. OUTCOME MEASURES: Sleep-onset latency (SOL), within-sleep wakefulness (WSW), rapid eye movement sleep (REM), slow-wave sleep (SWS), peak expiratory flow rate (PEFR) and arterial oxygen saturation. RESULTS: SOL increased on theophylline--12 minutes (range 7-9 minutes) compared with placebo--6 minutes (range 3-11 minutes); WSW increased from 33 minutes (range 17-66 minutes) on placebo to 72 minutes (range 35-150 minutes) on theophylline. REM sleep was unaltered. SWS decreased in 10-12 patients, but this difference was not significant. Early morning PEFR was significantly better on theophylline in all study limbs. CONCLUSION: Our findings show that while once-daily, sustained-release theophylline improves bronchodilation in nocturnal asthmatics, it increases nocturnal wakefulness and decreases sleep efficiency during short-term treatment. This may, however, not be a long-term effect.     

Effect of sleep on changes in breathing pattern accompanying sigh breaths

We studied the effect of sleep on the characteristics of sigh breaths and the associated changes in breathing pattern in breaths following spontaneous sighs in 4 unrestrained dogs with an intact upper airway. The sigh breath was characterized by its large tidal volume (VT), long TI and TE in comparison with the control breath. The volume of the sigh breath was larger in awake sighs than in those recorded during non-REM (NREM) and REM sleep. The strength of Hering-Breuer reflex as determined by duration of the post-sigh apnea was similar in NREM and REM sleep. Sighs occurring during wakefulness, NREM and REM sleep were associated with augmented activity of the parasternal muscles during inspiration, and a persistent tonic abdominal muscle activity during the expiratory period. Breathing pattern in the post-sigh period was characterized by a smaller VT and longer TE in the first post-sigh breath in all sleep states (compared with the control breath), but the pattern returned to control level within the second or third post-sigh breath in both NREM and REM sleep. Sighs did not precipitate periodic breathing or other forms of abnormal breathing patterns in either wakefulness or sleep. We conclude that the respiratory control mechanisms stabilizing breathing after a sigh in the awake dog are intact in NREM and REM sleep.     

The Sterling-Gallant new allotropic form of silver detected in biological preparations containing cysteine

We investigated the relationship between hemodynamic changes in the cortex measured by near-infrared spectroscopy (NIRS) and the polysomnographic changes during sleep. Four healthy male volunteers participated in the study. Near-infrared spectroscopy measuring and polysomnographic recordings were done simultaneously during sleep. In many case, oxy-hemoglobin (oxy-Hb) decreased and deoxy-hemoglobin (deoxy-Hb) increased during the transition from wakefulness to sleep, and oxy-Hb increased toward deep sleep. Oxy-Hb and deoxy-Hb had larger fluctuations during REM sleep than those during non-REM sleep. During REM sleep, oxy-Hb often showed a lower level and deoxy-Hb showed a higher level than those during the preceding and following non-REM sleep.