Relationship between delta activity during all-night sleep and negative symptoms in schizophrenia: a preliminary study.
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Adult↗
Biomedical subjects
T Okuma
Publications and source records attributed to T Okuma.
Zopiclone pharmacodynamics: by monitoring event-related potentials and psychometric scores.
To investigate the pharmacological effects of zopiclone in the central nervous system, we monitored event-related potentials (ERPs, N100 and P300), the reaction time and the scores for subjective mental and emotional state (by using the Polarity Profile Questionnaire, PPQ) on 10 healthy right-handed male volunteers between 21 and 32 years old. Subjects were randomly allocated to receive a single oral administration of zopiclone 7.5 mg or placebo at the first-session, and the drug was crossed over at the second session 1 week later. ERPs, the reaction time and the psychometric scores were monitored at pre-drug, and 1, 3 and 5 hours after drug administration. In the zopiclone group, the reaction time was prolonged significantly at 1 hour after drug administration, the amplitudes of the ERPs significantly decreased at 1 and 3 hours after, and the PPQ scores showed significant changes. Maximum effects on the psychometric scores appeared later than those on ERPs and reaction time. Zopiclone decreased the arousal level and sensory sensitivity, and induced sedation through changes in subjective mental and emotional states.
Administration, Oral↗
[Improvement in the surgical results in cancer of the thoracic esophagus by application of pre- and post-operative chemotherapy combined with antineoplastic agent sensitivity tests].
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Combined Modality Therapy↗
A quantitative sleep-EEG study on the effects of benzodiazepine and zopiclone in schizophrenic patients.
Polysomnographic examinations (PSG) were performed on 6 male schizophrenic outpatients who were being treated with benzodiazepine (BZD) hypnotics in combination with neuroleptics and 6 healthy male volunteers. In schizophrenic subjects, zopiclone (ZPC), 15 mg/day, was substituted for the BZD hypnotics, and PSGs were recorded again during ZPC therapy. All-night sleep stage scoring was carried out by visual analysis, and computerized period-amplitude analysis of sleep EEG was also performed. The schizophrenics showed marked reduction in the amount of slow-wave sleep (SWS) and in the number of delta half-waves during all-night sleep, especially those with higher amplitude, as compared to the normals. The number of delta half-waves in the patients was markedly reduced during the first sleep cycle. The average amplitude of delta half-waves during all-night sleep in the schizophrenics was significantly lower than that in the normals. The half-wave count of total delta waves in the schizophrenics was higher during treatment with ZPC than with BZDs, although no significant differences were observed in the amount of SWS between the two treatments. Soundness of sleep in the subjective sleep assessment was better evaluated during treatment with ZPC than BZDs. These results suggest that reduction of SWS in schizophrenia may be attributable mainly to the decrease in the number of delta waves with higher amplitude and that ZPC may induce deeper sleep in schizophrenics than BZDs.
Adult↗
The present and the future of sleep research in Asia.
In recent years, recognition of the importance of sleep, not only as a health problem but also as a social problem, has brought about worldwide growing interest in sleep and sleep research. In Asian countries, the number of sleep researchers is increasing rapidly and as a result the Asian Sleep Research Society (ASRS) was founded in 1994. This paper reviews the main topics of basic and clinical sleep research which have been investigated recently in Japan and in Asian countries. The subjects of sleep research in Asia in the future will be, in principle, similar to those in other countries of the world. However, the author suggests several subjects which are more or less specific to Asia and which should be studied in association, such as epidemiological longitudinal study of sleep disorders in developing countries, characteristics of sleep and dreaming in oriental culture and philosophy, etc. The roles of ASRS in dissemination of information, promotion of training and education, and enlightenment of public and government were also emphasized.
Asia↗
[Study of zopiclone with quantitative EEG analysis and topography].
Zopiclone is a cyclopyrrolone derivative which possesses hypnotic activity. This drug is known to increase the slow sleep stage compared to benzodiazepines in polysomnography. The subjects were 10 right-handed healthy male volunteers aged 21-23 years. Double-blind crossover trials with placebo control were conducted in a random sequence at intervals of 1 week. Zopiclone 7.5 mg and placebo were administered as single oral doses. Three-minute vigilance controlled EEGs at before and at 1, 3, and 5 h after drug administration, and the response times were recorded. One minute out of the 3-minute EEGs was analyzed with FFT and the power spectrum was obtained. Then the absolute amplitude power (microV) was calculated. These results were subjected to Student's t-test (double difference) and displayed with topographic maps (t statistic significance probability mapping). Zopiclone prolonged the latency of the response time, and increased the amount of delta absolute amplitude power over the right central region, beta 1 absolute amplitude power over the left central region and beta 2 absolute amplitude power over the right central area along with decreased alpha absolute amplitude power over the occipital region and theta power over the left frontal pole area after 1 h, when the peak pharmacological effect was expected. The EEG profiles of zopiclone were different from that of diazepam reported previously concerning the increase in delta activity.
Adult↗
Effects of zopiclone on sleep and symptoms in schizophrenia: comparison with benzodiazepine hypnotics.
Sleep variables and psychiatric symptoms were investigated in 6 male chronic schizophrenic outpatients. The patients were being treated with benzodiazepine (BZD) hypnotics for more than 8 weeks, and BZDs were replaced with zopiclone (ZPC) 15 mg/day. Polysomnographic examinations, subjective sleep assessments and BPRS scoring were performed during BZD therapy and at the end of 8 weeks of ZPC therapy. The doses of neuroleptics and anticholinergic agents remained fixed throughout the study. The amount of slow-wave sleep (SWS) was markedly small and that of stage 1 sleep was moderately large during BZD therapy. The amount of stage 1 was smaller and that of stage 2 was larger during treatment with ZPC than BZDs. There were no significant change in the amount of SWS between the treatment. Half of the patients exhibited a sleep-onset REM period (SOREMP) during ZPC therapy. Both total BPRS score and negative symptom score were lower during treatment with ZPC than BZDs. These results suggest that ZPC may be more beneficial in treating schizophrenic insomnia than BZD hypnotics and that reduced SWS and SOREMP may be partly involved in the pathophysiology of schizophrenia.
Adult↗
Preoperative chemotherapy for esophageal cancer based on chemosensitivity testing.
To examine the role and significance of in vitro chemosensitivity testing on cells cultured from endoscopic biopsy specimens, we evaluated outcomes in 57 patients with squamous cell carcinoma of the thoracic esophagus. Over 3 1/2 years, 57 patients were treated with a single course of preoperative combination chemotherapy based on the results of chemosensitivity testing utilizing eight antineoplastic agents. A radiologically evident response (partial response) was seen in 23 patients (40.4%) and histologic effects on grade IIb tumors were seen in six patients (10.5%). The median survival time of all 57 patients was 16.3 months. The median survival time of nine patients who received palliative resection was 4.5 months. The median survival times after curative resection of the 19 patients with a partial response and 29 patients with no response were 27.7 months and 17.3 months, respectively (p < 0.009). The most frequent combination chemotherapy used was cis-dichlorodiammine platinum (II) vindesine/5-fluorouracil, and a high rate of response was noted after therapy with etoposide and 4'-D-tetrahydropyranyl-doxorubicin. Chemosensitivity testing appears to be useful in selecting preoperative chemotherapeutic agents for patients with esophageal cancer, decreasing tumor recurrence after surgery and resulting in more partial responses than conventional chemotherapy.
Adult↗
Preoperative in vitro chemosensitivity test of esophageal cancer with endoscopic specimens.
BACKGROUND: From January 1990 to June 1991, the authors tested in vitro chemosensitivity before surgery with endoscopic biopsy specimens from 23 patients with intrathoracic esophageal cancer. METHODS: The authors tested eight anticancer agents using the dye exclusion method, and all 23 patients received chemotherapy with the most sensitive three drugs according to the results of the chemosensitivity test. RESULTS: Ten patients (43.5%) had a tumor reduction of more than 50% on radiologic studies, and 4 patients (17.4%) had a good histologic effect. CONCLUSIONS: The chemosensitivity test is useful in selecting preoperative chemotherapeutic agents for patients with esophageal cancer.
Adult↗
Memory and cognitive impairments in a case of long-term trihexyphenidyl abuse.
We present a case of long-term trihexyphenidyl (THP) abuse in which memory and cognitive impairments were observed 23 years after the commencement of medication. This case showed a dramatic improvement after withdrawal of THP. Clinical course during admission was followed with psychometric testing and laboratory examinations. The fact that the patient showed no evidence of lowered alertness during the clinical course raises the possibility that THP can primarily induce impairment of memory and cognitive functions. This is supported by the findings on the resting EEG of the patient. This case emphasizes the need to exercise caution in prescribing high doses of anticholinergic agents for long periods, particularly in elderly patients with underlying brain pathology.
Cognition Disorders↗
Pharmaco-EEG mapping of diazepam effects using different references and absolute and relative power.
The effects of diazepam on the EEG were studied by means of EEG topographic mapping, using recordings with four different references. Subjects were ten healthy, right-handed, male volunteers aged 21-25 years. Double-blind crossover trials with a single oral dose of 10 mg diazepam and placebo controls were conducted in random sequence at intervals of one week. Four referential derivations--ipsilateral earlobe (A1A2), average reference (AV), source derivation (SD), and balanced noncephalic electrode (BNE)--were used. One-minute vigilance-controlled EEGs before drug administration and two hours after drug administration were analyzed using Fourier transformation; absolute power and relative power were calculated for four frequency bands. Diazepam caused a widespread increase of beta-frequency relative power, and a widespread decrease of theta-frequency absolute power when A1A2 and SD were taken as references. From the comparison of different reference electrodes we conclude that the selection of the reference and of spectral parameters (absolute power or relative power) play an important role in pharmaco-EEG studies.
Adult↗
Effects of carbamazepine and lithium on affective disorders.
Characteristics of the responders and nonresponders to prophylactic treatment with carbamazepine (CBZ) or lithium (Li) were investigated in a retrospective study of 215 bipolar disorder patients who had received more than 2 years of CBZ or Li treatment in Japan. Patients of mania-dominant type, with isolated occurrence of manic and depressive episodes, with onset of the illness below 30 years of age, and with atypical symptomatology, tended to respond favorably to CBZ. Rapid cyclers and patients with a past history of rapid cycling and with a continuous recurrence of episodes responded unfavorably to CBZ. Patients of mania-dominant type also showed a favorable response to Li, while patients with a continuous-type course, with rapid cycling, and a past history of rapid cycling, as with CBZ, tended to respond unfavorably to Li.
Adolescent↗
Prognosis in esophageal carcinoma with cervical lymph node metastases.
BACKGROUND: The purpose of this study was to assess cervical lymph node (C-LN) metastases and to examine whether the site of the C-LN metastasis impacts on survival of the patient with thoracic esophageal cancer. METHODS: Transthoracic esophagectomy and three-field dissection (mediastinal, abdominal, and C-LN) followed by esophageal reconstruction were performed on 68 patients with squamous cell carcinoma of the thoracic esophagus who were seen at our institution from 1983 to 1990. RESULTS: C-LN metastasis was seen in 20 (29.4%) patients, and the survival curve of the 20 patients with positive C-LN metastasis was not significantly different from that of the 48 patients without positive C-LN metastasis. The survival curve of patients (n = 7) with positive node limited to recurrent laryngeal nerve chain node (RLN group) was significantly better than that of patients (n = 13) with positive internal jugular nodes including supraclavicular nodes (IJN group) (p = 0.010; generalized Wilcoxon). This was because there were more patients in the IJN group (84.6%) than in the RLN group (28.6%) (p = 0.022) who had five or more positive nodes in the three fields. CONCLUSIONS: The results suggest that RLN should not be defined as M1 but as N1 in thoracic esophageal cancer.
Age Factors↗
On the psychophysiology of dreaming: a sensory image--free association hypothesis of the dream process.
A psychophysiological hypothesis of the dream process during REM sleep called "a sensory image-free association hypothesis" is proposed. It is assumed that a state with a sustained EEG pattern of drowsiness (non-REM stage-1) and muscle atonia produces a stream of disorganized and vague thinking as a background mentation during the REM sleep. The phasic excitation of the brain occurring concurrently with the burst of rapid eye movements (REMs) activates the hippocampal-neocortical memory system and draws out sensory images from the memory reservoir of the brain. The dreamer makes a freely organized association about the successive sensory images and makes up a dream story. This hypothesis is compatible not only with the recent neurophysiological findings but also with traditional psychological interpretation of the dream content.
Animals↗
Effects of indeloxazine hydrochloride on sleep in normal humans.
The effects of 40 mg of indeloxazine hydrochloride, a cerebral metabolic enhancer, on sleep were investigated in 6 healthy male students. Polygraphic recordings were made for 8 consecutive nights on each subject. An inert placebo was given on the first 3 nights and on the 7th and 8th nights, and 40 mg of indeloxazine was administered on the 4th, 5th and 6th nights. Drug and placebo were administered orally at 21:30 h, and the recording of polysomnograms started at 22:00 h and ended at 8:00 h the next morning. The polysomnograms were evaluated by computerized automatic analysis using the interval histogram method. Indeloxazine prolonged both sleep latency and REM latency, and increased stage 1 sleep, but decreased stages 3, 4 and REM sleep. A significant increase of REM sleep was observed on the 7th and 8th recovery nights. No obvious changes were shown in the subjective assessments after administration of the drug. These results suggest that the effects of indeloxazine on sleep are similar to those of the tricyclic antidepressants. Furthermore, polysomnographic examinations might be useful in evaluating the pharmacological properties of cerebral metabolic enhancers.
Adult↗
Comparison of the antimanic efficacy of carbamazepine and lithium carbonate by double-blind controlled study.
A multi-institutional study comparing the antimanic effect of carbamazepine (CBZ) and lithium carbonate (Li) was performed using a double-blind group comparison design in a series of 105 patients with bipolar disorders. CBZ and Li were given for four weeks using a fixed-flexible method at an equipotent dose ratio of 1:1, starting from an initial dosage of 400 mg with a maximum dosage of 1200 mg. The final global improvement rate, based on the number of cases showing moderate to marked amelioration of manic symptoms, was 62% in the CBZ group and 59% in the Li group, with no significant difference being found between the two groups. Incidence of cutaneous side-effects was significantly higher in the CBZ group. The mean daily dosage and serum level of CBZ in the fourth week were 674 +/- 239 mg and 7.3 +/- 2.4 micrograms/ml respectively; these were within the therapeutic range. The daily dose and serum level of Li, however, were 710 +/- 239 mg and 0.46 +/- 0.22 mEq/l, and the Li level seemed to be too low to compare its therapeutic effect with that of CBZ. Prior to the present study, approximately 80% of the patients in both groups had been receiving antipsychotic medication, equivalent to 8.0 mg of haloperidol on average, without favorable response. This medication was maintained unchanged during treatment. While the shortcomings of the present study limit the interpretation of the data, it may be suggested that the usefulness of CBZ as a drug for the treatment of manic states is comparable to that of Li.
Adolescent↗
[An autopsy case of glioblastoma occurred in the region after lobotomy].
The authors describe an autopsy case of glioblastoma occurred after 38 years received lobotomy. The patient was a 72 year-old male, who received lobotomy at 34 year old against schizophrenia. CT scan taken at 72 year old showed irregular low density areas without mass effect in the bilateral frontal white matter adjacent to the anterior horn. After 4 months, the signs of intracranial hypertension were observed and his consciousness was disturbed abruptly. CT scan revealed ring enhancement with marked mass effect in the left frontal lobe. A biopsy specimen from the tumor showed a picture of anaplastic astrocytoma. Family rejected the remission maintenance treatment. The patient died 3 months later the onset. At autopsy, a large tumor occupied in the left frontal lobe was recognized. The tumor demarcated poorly from the cerebral tissue and invaded into the left anterior cingulate gyrus and the corpus callosum. Histologically, tumor cells composed of fibrillary, gemistocytic and multinucleated astrocytes. GFAP, NSE and vimentin were found in large cells. Histological diagnosis was glioblastoma. It was suggested that the tumor occurred from the region around a cyst of prefrontal lobotomy in the left frontal lobe. In the right frontal lobe, a large cyst in size of 30-18 mm was present in the centrum semiovale. The wall of cyst was composed of layer of glial scar tissue. The origin of the cyst was discussed.
Aged↗
Clinical efficacy of carbamazepine in affective, schizoaffective, and schizophrenic disorders.
The therapeutic effects of carbamazepine (CBZ) were evaluated in 103 patients with affective disorders, 54 with schizophrenic disorders, and 26 with schizoaffective disorders by a multi-institutional open study. The rate of marked and moderate improvement was 72.8% in affective disorders, 54.6% in schizophrenic disorders, and 61.5% in schizoaffective disorders. Symptom items of the Clinical Psychopharmacology Research Group rating scale for mania showed significant improvement in the patients with affective disorders as well as in those of the other two groups. In the Brief Psychiatric Rating Scale as applied to patients with schizophrenic or schizoaffective disorders, symptom items related to affect and emotion showed significant improvement. The antimanic efficacy of CBZ was also noted in many poor responders to lithium. Side-effects were observed in 82 patients (44.8%), and abnormal laboratory findings in 37 patients (44.8%), and abnormal laboratory findings in 37 patients. The present study seems to confirm the usefulness of CBZ for the treatment of affective disorders and in some cases, of schizophrenic and schizoaffective disorders.
Adult↗