Inhibition of K(+)-evoked release of rat striatal 5-hydroxytryptamine by an atypical antidepressant: trazodone.

Using microdialysis, extracellular concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the striatum of rats. In rats given trazodone, m-chlorophenylpiperazine dihydrochloride, or imipramine, the concentrations of 5-HT were unchanged. 5-HIAA in trazodone- or imipramine-treated rats, however, was respectively, decreased to 80 or 65% of preinjections levels. When the potassium concentration (K(+)) was increased up to 150 mmol/l in the perfusate, the concentrations of 5-HT increased to about ten times the basal levels in the rats given saline. In rats treated with trazodone, K(+)-evoked elevations of 5-HT were less than five times the basal level. Multiple trazodone administrations prolonged the duration of inhibition of 5-HT release. In rats treated with other drugs, the K(+)-evoked 5-HT release was not affected. These observations suggest that trazodone itself might reduce 5-HT neural transmission.

Clozapine, but not haloperidol, reverses social behavior deficit in mice during withdrawal from chronic phencyclidine treatment.

Phencyclidine (PCP) reduced social behavior (SB) in a dose- and time-dependent fashion. However, no such SB deficit was observed on repeated treatment with methamphetamine for 14 days. The SB deficit produced by treatment with PCP (10 mg/kg/day) for 14 days, which persisted for 28 days after withdrawal, was attenuated by clozapine (10 mg/kg/day) given for 7 days, whereas haloperidol for 7 days had no effect. Clozapine, but not haloperidol, alone at the same treatment dose increased SB in saline-treated mice. These results suggest that the proposed PCP model in mice will provide a tool to test beneficial effects of atypical antipsychotics on social dysfunction in schizophrenia, and contribute to our understanding of the mechanisms by which clozapine improves SB deficit.

Habitual snoring in an outpatient population in Japan.

In order to investigate the occurrence and history of sleep problems in Japan, the 11-Centre Collaborative Study on Sleep Problems (COSP) project was carried out. Complaints of snoring are examined, and its prevalence, risk factors and screening reliability are discussed. The subjects who participated in the study were 6445 new outpatients from a general hospital. They were asked to answer a sleep questionnaire that consisted of 34 items with seven demographic items; each item was composed of four grades of frequency. In order to offset possible seasonal variations in sleep habits, data were collected across four seasons. Sleep patterns, insomnia, hypersomnia, parasomnia and circadian rhythm sleep disorders were covered. Habitual snoring was seen in 16.0% of males and 6.5% of females. Male predominance was noted. From these data, the relationship between habitual snoring and sleep complaints was statistically analyzed. Habitual snorers (HS) were observed to wake up more frequently during sleep (17.8% of males, 21.5% of females) than were non-habitual snorers (NHS; 6.6% of males, 9.7% of females). Mid-sleep awakening of HS was also more frequent than it was for NHS; however, there were no differences in difficulty in falling asleep and early morning awakening. Body mass index, cigarette smoking and alcohol consumption were also correlated with habitual snoring.

Sleep problems in the aged in relation to senility.

As a part of an epidemiologic survey of dementia in a community of aged persons, correlation between sleep complaints and physical illness and senility were studied. A total of 3302 randomly sampled aged individuals(aged > or = 65 years) were studied using a questionnaire. In this sample the prevalence of poor sleep and habitual snoring did not increase with age. The prevalence of excessive daytime sleepiness showed an increase with age. Male predominance of habitual snoring and female predominance of poor sleep were observed. Female predominance of excessive daytime sleepiness was noted among the aged 70 and over. Age-related excessive daytime sleepiness was significantly correlated with senility.

Differences in arousal response between aged and middle-aged patients with obstructive sleep apnea syndrome.

The aim of this study is to show the clinical significance of the differences in arousal response at a termination of apnea/hypopnea between aged and middle-aged patients with obstructive sleep apnea syndrome (OSAS). We polygraphically assessed electrocardiographic (ECG) and electroencephalographic (EEG) arousal. Electrocardiographic arousal was defined as an abrupt increase in heart rate at a termination of apnea/hypopnea. Our findings showed that EEG and ECG arousal at a termination of apnea/hypopnea were significantly suppressed in aged patients with OSAS, which might provide useful information on the pathophysiology, of OSAS.

Daytime sleepiness and automobile accidents in patients with obstructive sleep apnea syndrome.

We evaluated the rate of automobile accidents and daytime sleepiness using the Epworth sleepiness scale (ESS) in 44 patients with obstructive sleep apnea syndrome (OSAS). We defined the automobile accident score as a sum of two points for every one automobile accident and one point for every near-miss accident. Automobile accidents and near-misses were found in 54.5% and 50.0% in patients with OSAS. Automobile accident score was significantly correlated with the ESS score (r=0.56, P < 0.01). Our findings suggest that ESS score may be useful in detecting patients with the potential risk of automobile accidents associated with daytime sleepiness.

A survey of habitual snoring in centenarians.

OBJECTIVE: To ascertain whether centenarians in the surveyed group would be nonhabitual snorers. DESIGN AND SETTING: A cross-sectional survey of centenarians residing in the Aichi Prefecture of Japan. PARTICIPANTS: A total of 103 centenarians (21 men and 82 women). MEASUREMENTS: Questionnaire on sleep habits, breathing, and snoring. RESULTS: Nineteen centenarians (18.4%; 5 men and 14 women) were habitual snorers and two (1.9%) were suspected of having sleep apnea syndrome because of the presence of heavy snoring and nocturnal respiratory arrest. CONCLUSION: Most centenarian subjects were nonsnorers and without breathing pauses during sleep; their snoring rates were no different from those of younger aged older adults in the same population.

Ultra-low-field magnetic resonance imaging in upper airways obstruction in sleep apnea syndrome.

The hypothesis that the sites of upper airways obstruction (UAO) are varied in a patient with obstructive sleep apnea syndrome (OSAS) among different sleep stages is studied. Four patients with OSAS underwent ultra-low-field magnetic resonance imaging (MRI) with a field strength of 0.064 Tesla provided real-time images and generated less noise and necessitated less strict magnetic isolation compared with conventional high-field MRI. After the fixed end-apneic sleep stage was determined, the polysomnogram was switched off and ultra-low-field MRI was commenced. The effects of continuous positive airway pressure (CPAP) on the upper airway patency in the deepest sleep stage obtained for each patient was assessed. Upper airway obstruction was found at the level of the palatopharynx (PP) at sleep onset extended to the glossopharynx (GP) during rapid eye movement (REM) sleep in two cases and during NREM sleep in one case. This combined PP and GP obstruction was observed from sleep onset and remained unchanged in one case. The patent upper airways were observed during treatment with CPAP during REM sleep in two patients and during stage two of NREM sleep in the other two patients. It can be concluded that the sites of UAO vary in a patient with OSAS in different sleep stages. The results also suggest the use of the ultra-low-field MRI in order to visualize the dynamic and real-time behaviors of the upper airways during sleep in patients with OSAS.

Changes in cerebral oxygenation and hemodynamics during obstructive sleep apneas.

OBJECTIVE: To evaluate changes in cerebral tissue oxygenation and blood volume during obstructive sleep apnea (OSA). METHODS: We studied eight men with moderate to severe OSA by near-infrared spectroscopy (NIRS) simultaneously with polysomnography during nocturnal sleep (five patients) and daytime naps (three). RESULTS: In all patients, a consistent decrease of oxyhemoglobin (OxyHb) and increases of deoxyhemoglobin and total hemoglobin (TotalHb) in the regional cerebral tissue were observed during the episode of OSA at every sleep stage. Changes in each hemoglobin and apnea duration were significantly (p<0.01) more remarkable during rapid eye movement (REM) sleep than non-REM (NREM) sleep. Significant correlations of changes in OxyHb and TotalHb during the apneic episode with apnea duration were found during both NREM and REM sleep (p<0.01). CONCLUSIONS: Since TotalHb is used as an indicator of blood volume in the NIRS technique and the venous return is reported to increase during OSA, it is assumed that cerebral blood flow (CBF) increases during the episode of OSA. Because a decrease in OxyHb was observed and brain activity is reported to decrease during OSA, it is supposed that oxygen supply to the brain tissue decreases rather than oxygen consumption in the brain increases. The results of this study indicate that possibly increased CBF could not compensate for reduced arterial oxygen saturation and cerebral tissue hypoxia may occur during the episode of OSA.

Long-term follow-up study of 10 adolescent patients with sleep-wake schedule disorders.

Therapeutic trials for sleep-wake schedule disorders have been described, but a long-term follow-up of adolescents with such disorders have not previously been reported. We investigated 10 adolescents with sleep-wake schedule disorders who had formerly received intensive treatment. The investigation was carried out with detailed questionnaires about current sleep conditions and social state. The follow-ups were obtained from 1.2 to 11.2 years after the initial treatment. Three cases have remitted, and six have improved in illness severity. All patients showed improvement in social adaptation. Improvement in the social adaptation level was greater than improvement in the illness severity level. More cases should be studied to learn what factors influence the prognosis of these disorders.

Long-term course of adult patients with delayed sleep phase syndrome.

A response to treatment and long-term course of 14 adults with delayed sleep phase syndrome were investigated with the use of their hospital records and mailed questionnaires. Six patients treated with chronotherapy showed full recovery just after the treatment. In three of them the delay of sleep phase relapsed one year afterwards. Four of five patients treated with pharmacotherapy alone showed partial recovery. Six of nine patients followed for periods of longer than three years after treatment showed good prognoses, though all of them still had a mild phase delay and had to shorten their sleep time in order to work full-time. The three others had poor prognoses and one of them was under psychiatric treatment for affective instability. These findings suggest that a long-term follow-up is needed to judge the effect of the treatment.

Daily activity and persistent sleep-wake schedule disorders.

1. Patients with disorders of entrainment to external time cues such as delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake syndrome (HNS) were treated with non-pharmacological interventions and/or pharmacological agents. 2. Resetting the circadian clock with chronotherapy was easy in all DSPS patients, but it was not as easy to maintain the reset rhythm without additional therapy. Triazolam was effective in treating the phase delay that reappeared after chronotherapy. 3. Vitamin B12 (methylcobalamin) was strikingly effective in some patients with DSPS or HNS. 4. All the adolescent patients who complained of inability to attend school finally returned to their classes after treatment. Maintaining the reset rhythm in adolescent patients was easier than in adults.

Treatment of persistent sleep-wake schedule disorders in adolescents with methylcobalamin (vitamin B12).

Two adolescent patients suffering from persistent sleep-wake schedule disorders appear to have responded to treatment with vitamin B12 (methylcobalamin). A 15-year-old girl with delayed sleep phase syndrome (DSPS) and a 17-year-old boy with hypernychthemeral syndrome complained of not being able to attend school despite many trials of medication. The improvement of the sleep-wake rhythm disorders appeared immediately after the administration of high doses (3,000 micrograms/day) of methylcobalamin. Neither patient showed any laboratory or clinical evidence of vitamin B12 deficiency or hypothyroidism (which can cause B12 deficiency). Serum concentrations of vitamin B12 during treatment were in the high range of normal or above normal. The duration of the sleep period of the DSPS patient decreased gradually from 10 hours to 7 hours, and the time of sleep onset advanced from 2 a.m. to midnight. The period of the sleep-wake cycle of the hypernychthemeral patient was 24.6 hours before treatment and 24.0 hours after treatment. The relationship between the circadian basis of these disorders and vitamin B12 and its metabolites is discussed.

Unusual cases of presenile dementia with Fahr's syndrome.

Three patients with an unusual type of presenile dementia were studied. Atypical clinical pictures emerged from an evaluation of these cases. Their symptoms and signs were thought to be neither those of Alzheimer's disease nor those of Pick's disease but a partial mixture of those of both diseases. The neuropathological changes were characteristic and the common findings were as as follows: the absence of senile plaques, the widespread presence of numerous neurofibrillary tangles, a calcareous deposition of Fahr's type, a circumscribed cerebral atrophy in the temporal or/and frontal lobes, a moderate or severe demyelination and fibrous gliosis in the white matter of the atrophied areas, and a slight or moderate neuronal loss in the nucleus basalis of Meynert. Similar cases reported previously were reviewed.

An unusual case of Pick's disease.

A man aged 64, with a history of chronic trichloroethylene intoxication, presented early headache, impairment of memory, and "stehende Redensarten", later on mental deterioration with muteness and oral tendency. He died of bronchopneumonia. The brain was studied by light and electron microscopy. Numerous inflated cells, intraneuronal argentophil Pick bodies and central chromatolysis of neurons were found throughout the cerebral cortex. Widespread diffuse fibrillary gliosis was the finding bearing a striking resemblance to "progressive subcortical gliosis". Severe loss of nerve cells was observed in the temporal lobe (except the posterior of T 1) and moderate or mild loss in the gyrus rectus, insula, gyrus cinguli, and partial areas of the frontal, parietal, and occipital lobes. By electron microscopy, the argentophil Pick bodies consisted of a conglomeration of randomly arranged short 100-150 A filaments, ribosomes, vesicles, mitochondria, and scanty paired helical filaments. The present case was considered to represent a rare case of Pick's disease of the temporo-fronto-parieto-occipital type or panencephalic type.