Treatment of sleep apnea with prosthetic mandibular advancement (PMA).

Nine males with sleep apnea DOES syndrome and three males with sleep apnea DIMS syndrome were treated with prosthetic mandibular advancement (PMA). The method uses a prosthesis, which is designed to advance the mandible 3-5 mm to prevent upper airway occlusion during sleep. The apnea index in the obstructive-type apnea and the percentage of time spent in obstructive apnea decreased significantly with PMA. Although the apnea index showed merely a tendency to decrease in central apnea (p < 0.1), the percentage of time spent in central apnea decreased significantly with PMA. A marked improvement in sleep structures was observed with PMA; a significant increase was seen in total sleep time, percent slow wave sleep (SWS) and percent rapid eye movement (REM) sleep, and the time spent in intra-sleep awakening decreased remarkably. PMA had excellent effects on snoring, and daytime hypersomnolence was reduced in almost all patients. Moreover, a survey on the therapeutic effects of PMA on sleep apnea syndrome and problems associated with wearing PMA was performed with a questionnaire for the sample of nine DOES patients and an additional 22 patients who were treated over a long time. The therapeutic effects could be maintained without any problems in about 2/3 of these patients. The therapeutic mechanisms of PMA in its reduction of both obstructive and central apnea are discussed.

Individual variations in the effects of flurazepam, clorazepate, L-dopa and thyrotropin-releasing hormone on REM sleep in man.

The comporative effects of flurazepam, clorazepate, L-dopa, and thyrotropin-releasing hormone (TRH) on REM sleep were investigated in normal, healthy adults. A single dose of each drug was given orally to the subjects 30 min before bedtime. A dose of 30 mg flurazepam significantly decreased REM sleep-time when compared to the mean baseline record. No change was noted in REM sleep-time on the clorazepate (15 mg) night, L-dopa (1000 mg) night, or TRH (2 mg) night, when compared to the mean baseline record. Because large individual variations were found in REM sleep time on each drug night, and in percentage increase in REM sleep following partial differential REM deprivation (PDRD), correlation was investigated between them. The percentage decrease in REM sleep during flurazepam was found to have a significant negative correlation with the percentage increase in REM sleep after PDRD in individual subjects. Although there was no significant change in REM sleep on TRH night when compared to the mean baseline record, a similar significant negative correlation was noted. On the L-dopa night, there was a tendency toward a negative correlation between them. No significant correlation was noted on the clorazepate night.

Effects of antibiotics, minocycline and ampicillin, on human sleep.

The effects of two kinds of antibiotics, minocycline (MNC) and ampicillin (AB-PC), on human sleep were investigated on 19 healthy male students to test for a relationship between human sleep and protein synthesis. These drugs and placebos were capsulated identically in appearance and were given to the subjects using the single blind method. MNC has been proven to prevent protein synthesis whereas AB-PC does not inhibit protein synthesis, and both antibiotics are commonly used in clinical practice. With the administration of a single dose of 200 mg of MNC, an apparent decrease in slow wave sleep (SWS) was revealed on the drug night and the effects lasted through the following two consecutive nights being given a placebo. REM sleep was not reduced on all the recording nights. On the other hand, both SWS and REM sleep were not reduced with the administration of a single dose of 500 mg of AB-PC. These results are different from those previously obtained from animal experiments since many kinds of protein synthesis inhibitors have been proven to suppress mainly REM sleep in animals. It might be supposed that the species difference may be responsible for this difference, and that some proteins or polypeptides induce human sleep, especially SWS.

Biorhythm of core temperature in depressive and non-depressive alcoholics.

Core temperature was longitudinally evaluated during the day- and nighttime in six non-depressive and in four depressive alcoholics who had been abstaining from alcoholic beverages. The least squares spectrum method was employed for detecting the periods and acrophase of the circadian rhythm of core temperature. Although normal periods were observed in all the patients throughout the study, an abnormal acrophase was found in many patients, especially in depressive alcoholics. On the 3rd and 4th days after alcohol withdrawal, all of the four depressive alcoholics showed a phase advance of the circadian rhythm, and three patients of the six non-depressive alcoholics exhibited an abnormal acrophase. On the 21st and 22nd days after alcohol withdrawal, a normal acrophase was observed in two patients of the four depressives and in four of the six non-depressives. The mean core temperature was higher in the depressives than in the non-depressives on the third and fourth days after alcohol withdrawal.

Terminal sleep following delirium tremens in chronic alcoholics--polysomnographic and behavioral study.

Delirium tremens frequently ends with behaviorally deep sleep after which the patient has usually recovered from the withdrawal state. This sleep has been called "terminal sleep" or "critical sleep". In the present study terminal sleep was investigated in 14 chronic alcoholics. Polysomnographic recordings were undertaken during terminal sleep and the patients' behavior was observed after the patients awoke from terminal sleep. A marked decrease in stages 3 and 4 sleep was found in all the patients. Sleep cycles were regularly observed in 10 patients, while in the remaining four patients sleep cycles were not observed in terminal sleep. The patients who exhibited regular sleep cycles had fully recovered from delirium tremens after they awoke from terminal sleep, and they never relapsed into delirium tremens afterwards. In contrast, the patients who demonstrated terminal sleep in which sleep cycles were not observed revealed inactive and sometimes disoriented behavior suggesting slight disturbances of consciousness. These patients developed delirium tremens repeatedly thereafter. Therefore, terminal sleep can be divided into two different types. One is recovery sleep from sleep deprivation induced by delirium tremens, in which sleep cycles are observed. The other is not sleep, but a state which is indicative of disturbances of consciousness.

Polysomnographic study of terminal sleep following delirium tremens.

Polysomnographic recording was performed during terminal sleep following delirium tremens (DT) in nine chronic alcoholics. After terminal sleep all the alcoholics fully recovered from DT. The duration of terminal sleep and DT differed among patients, but no significant correlation was found between the two. The most prominent feature in teh different stages of terminal sleep was a considerable decrease in slow wave sleep, especially stage 4 sleep. A slight decrease was observed in REM sleep, while stages 1 and 2 increased. A small amount of stages 1-REM and 2-REM was observed and a statistically significant correlation was noted between the appearance of these sleep stages. Intermittent wakefulness occurred in many patients. The disappearance of sleep cycles was observed in some patients. Therefore, terminal sleep following DT probably consists of recovery sleep from sleep deprivation caused by DT and disturbances of consciousness. Sleep cycles regularly occur in the former, but not in the latter.

Serum folic acid levels and antipyrine clearance rates in smokers and non-smokers.

Serum folic acid (FA) levels and antipyrine clearance rates were determined in 15 healthy male subjects who had not been administered any drug and alcohol for a month preceding the study. Eight of the 15 subjects smoked cigarettes daily while the remaining seven did not. The serum FA levels were measured by Lactobacillus casei bioassay. The antipyrine clearance rates were estimated in plasma or saliva obtained after oral administration of antipyrine for evaluating the activity of hepatic microsomal oxidase. The serum FA levels in the smokers were significantly lower than those in the non-smokers and the antipyrine clearance rates were significantly higher in the smokers compared with the non-smokers. The increase of the antipyrine clearance rates in the smokers was supposed to be caused by an increase in the activity of hepatic microsomal oxidase since it has been established that polycyclic aromatic hydrocarbons contained in cigarette smoke induce these enzymes. The association of the decrease in the serum FA levels and the increase of the antipyrine clearance rates was investigated.

Questionnaire relating to sleep paralysis.

A sleep survey was conducted on 8162 citizens. The cumulative experience rate of sleep paralysis was 39.6%. The initial occurrence of sleep paralysis peaked at age 16 years. In addition to being higher in young people than in older subjects, the incidence of sleep paralysis was also higher among women than among men, and was significantly higher among shift worker than non-shift worker, and among persons engaged in the nursing profession than those not engaged in the nursing profession. The experience rate of sleep paralysis demonstrated a strong correlation with the frequency of dreaming, the experience rate of nightmares, times and regularity of going to bed and waking up, and particularly with the degree of insomnia.

Changes in sleep pattern after sleep deprivation.

Total sleep deprivation (TSD) was performed for one night with 11 healthy male students and three-consecutive-recovery night-sleep was recorded. Special attention was paid to the analysis of the individual difference in SWS(min, %) on the baseline and recovery nights. The total sleep time increased on the first recovery night compared to the baseline, but it decreased significantly on the second and third recovery nights. Stage 1(%) decreased significantly on the first and second recovery nights. Stage SWS(min) showed a significant increase on the first recovery night, while SWS(%) increased significantly on the first and second recovery nights. As for Stage REM(%), there was no significant difference between the baseline and the recovery nights. There was a positive correlation between SWS(min) on the baseline and that on the recovery nights. SWS(%) also showed the same results as those obtained with SWS(min). Between SWS(min) in the baseline and the increase rate of SWS(min) on the first recovery night, there was a significant inverse correlation, while there was a tendency to inverse correlation on the second and third recovery nights. As to SWS(%), there was a significant inverse correlation between SWS(%) in the baseline and the increase rate of SWS(%) on the first and third recovery nights.

Individual variations in response of human REM sleep to amitriptyline and haloperidol.

The effect of amitriptyline and haloperidol on REM sleep was investigated in healthy human adults, with special attention to individual variations in these drugs' effects. In addition, an investigation was made of the rebound elevation of REM sleep occurring on the following night of partial differential REM deprivation (PDRD), again with emphasis being placed on individual variations in that effect. The administration of amitriptyline in a single oral dose of 25 mg was followed by an inhibition of REM sleep in all subjects. The per cent decrease in REM sleep was found to have a significant negative correlation with the per cent increase in REM sleep following PDRD in individual subjects. The amount of REM sleep during the recovery night following the night of amitriptyline medication tended to correlate with the per cent increase in REM sleep following PDRD in individual subjects. Haloperidol in a single oral dose of 1.5 mg caused REM sleep to augment in some subjects but inhibit in others. A significant correlation was noted to exist between drug-induced change in REM sleep and the per cent increase in REM sleep following PDRD.

Time course of saliva and serum melatonin levels after ingestion of melatonin.

Salival and serum melatonin levels after melatonin ingestion were measured by gas chromatography-mass spectrometry. Ingestion of 3 mg melatonin caused a marked increase in serum melatonin (3561+/-1201 pg/mL) within 20 min, followed by a gradual decrease, but the level still remained higher than the basal level at 240 min after the ingestion. The saliva melatonin 60 min after the ingestion showed the highest level (1177+/-403 pg/mL) which was one-third of the plasma level. The saliva melatonin level was highly correlated with the serum level throughout the experimental period (r=0.82, P=0.0001). These data indicate that the measurement of saliva melatonin level may be a suitable indicator for the melatonin secretion into general circulation.

Comparison of body temperature rhythms between healthy elderly and healthy young adults.

The fact that the elderly are usually aware of early sleep onset and early morning awakening shows that the phase of sleep-wake rhythms in the elderly is more advanced than that in young adults. Since it has been suggested that human sleep onset, morning awakening, sleep period and depth of sleep are highly influenced by body temperature rhythms, rectal temperature rhythms were analyzed in 7 healthy elderly and 7 healthy young adults under the condition with time cue. Although a significant 24-hour period was found in the rhythms for all subjects, the phase of the rhythms in the elderly was more advanced than in the young adults. Moreover, a significant inverse correlation was observed between age and acrophase time in the elderly.

Individual differences in compensatory rebound of REM sleep, with particular reference to their relationship to personality and behavioral characteristics.

In subjecting 14 healthy university students to partial differential rapid eye movement (REM) sleep deprivation (PDRD), the compensatory rebound of REM sleep during the next night was determined, and showed fairly substantial individual differences in the increased percentage of REM sleep time. This rate was approximately the same for the same individual for two sleep recordings. These individual differences had no positive correlation with the decreased rate of REM time in the PDRD nights or with the percentage of REM time in the baseline night. Therefore, the individual differences in the increased percentage of REM time can be presumed to reflect individual differences in need for deprived REM sleep. Next, we looked into the relationship between the individual subject's personality and behavior characteristics, and his increased percentage of REM time. This revealed that the individuals who were extrovertive, active, optimistic, showy, and who had many friends had significantly higher increases in the percentage of REM time than the individuals who were introvertive, neurotic, inactive, nervous, modest, and who had few friends. Also discussed was the neurophysiological and biochemical basis of the central nervous system as the background for the relationship between the personality and behavioral characteristics and the increased percentage of REM sleep time.

Effects of hCRH on sleep and body temperature rhythms.

We investigated the effects of human corticotropin-releasing hormone (hCRH) on the sleep structure and body temperature rhythms of seven healthy young men. Polysomnographic recordings were obtained and body temperatures were monitored continuously for 48 h in each subject following the intravenous administration of saline or of 100 micrograms hCRH. The administration of hCRH was associated with a significant phase-advancement in body temperature rhythm vs the saline control. The administration of hCRH affected non-rapid eye movement (NREM) sleep by reducing significantly slow wave sleep (SWS) and sleep efficiency, whereas the percentage of sleep stages 1 and 2 were increased significantly. These changes in body temperature rhythms and sleep structure induced by hCRH resembled those observed in patients with endogenous depression, except for the findings during rapid eye movement (REM) sleep. We hypothesize that a hypersecretion of hCRH in patients with endogenous depression may help to explain the changes in body temperature rhythms and sleep structure often reported in such patients.

Study on the effects of L-5HTP on the stages of sleep in man as evaluated by using sleep deprivation.

The effects of L-5HTP 200 mg on the EEG sleep pattern were investigated in normal subjects. When L-5HTP 200 mg was orally administered, only % S1 significantly decreased in comparison with the baseline. There was no change in any sleep stage on the first recovery night. On the second recovery night, % S1 significantly decreased, while % SR increased significantly. SWS did not show any change. The effects of L-5HTP 200 mg were investigated on the first recovery night after one night of sleep deprivation. SWS significantly increased on the first recovery night when a placebo was given, while this rebound increase of SWS disappeared and % S2 significantly increased on the first recovery night when L-5HTP was given. % SR significantly increased on the next night after the L-5HTP night.

Digital plethysmographic responses to auditory stimuli in patients with vibration disease.

Digital plethysmographic responses to auditory stimuli in 15 healthy men and 82 patients with vibration disease were analyzed in order to clarify the functional conditions of autonomic nervous system in this disease. The auditory stimuli given to healthy men caused a rapid decrease in the amplitude of the plethysmograms. After cessation of the auditory stimuli the decreased amplitude recovered to the control value within 30 sec. In the patients with vibration disease, however, the recovery of the decreased amplitude was delayed. The plethysmographic changes in the patients with vibration disease were divided into 4 types: normal (N), intermediate (I), delayed (D) and poor response (P) types. Each type of I, D and P was altered to type N by treatments consisting of therapeutic exercises, hot spring cures and so on. All healthy men showed type N. There were no significant differences between the time courses of the recovery of the plethysmographic changes and the amplitudes of the plethysmograms before the auditory stimuli. The results obtained seem to indicate that the autonomic nervous system in the patient with vibration disease is in disorder, and that the digital plethysmography with auditory stimuli is instrumental to detect the functional changes in the autonomic nervous system.

Study on the partial differential REM deprivation (PDRD).

With an aim to make observations on the rebound elevation of REM sleep, we have devised the partial differential REM deprivation (PDRD) method whereby the subjects are awakened forciby at a fixed time early in the morning. By this method, REM sleep is deprivated by about a half and stage 2 sleep by about one third of the baseline value; but stage SWS is not deprivated. When the test set of PDRD is performed repeatedly on an identical subject, the REM sleep time during PDRD night and recovery night is almost always constant. Our PDRD, we believe, is an excellent method that relieves the disconfort of the subject and the physical burden of research workers and yet is capable of measuring almost accurately the magnitude of rebound elevation of REM sleep in each subject.