Myasthenialike syndrome due to adverse effects of cibenzoline in a patient with chronic renal failure.
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Angina Pectoris↗
Biomedical subjects
E Matsushima
Publications and source records attributed to E Matsushima.
A psychophysiological study of the development of delirium in coronary care units.
This is a longitudinal investigation of the psychophysiological mechanism for the development of delirium in coronary care units (CCUs). Ten patients satisfying DSM-III-R diagnostic criteria for delirium (group D) and 10 controls (group C) were drawn from patients admitted to CCU. Electroencephalogram (EEG) and eye movement recordings were observed over the days that patients were admitted to CCU and on a control day of admission and compared for each group and between each day. In the D group, slowing of background EEG activity, particularly on day 2, and many R (rapid) group eye movements and RS type (rapid superimposed on slow) eye movements, particularly on day 3, were observed. That is, from days 2 to 3, EEG findings showed an improvement in consciousness, and eye movement recordings manifested signs of anxiety and tension. These psychophysiological findings can be used to explain the transition from prodromal delirium to obvious delirium, and are supported by clinical features.
Anti-Anxiety Agents↗
Determination of S-1 (combined drug of tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate) and 5-fluorouracil in human plasma and urine using high-performance liquid chromatography and gas chromatography-negative ion chemical ionization mass spectrometry.
A high-performance liquid chromatography (HPLC) and gas chromatography-negative ion chemical ionization mass spectrometry (GC-NICI-MS) method was developed for the analysis of the combined antitumor drug S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate) and active metabolite 5-fluorouracil in human plasma and urine. Tegafur was fractionated from biological fluids by extraction with dichloromethane and analyzed by HPLC. 5-Fluorouracil and 5-chloro-2,4-dihydroxypyridine were extracted with ethyl acetate from the residual layer after extraction of tegafur, and converted to pentafluorobenzyl (PFB) derivatives. Potassium oxonate was cleaned up with an anion-exchange column (Bond Elut NH2). The extracted potassium oxonate was degraded to 5-azauracil and converted to PFB derivatives. The PFB derivatives were analyzed by GC-NICI-MS. A stable isotope was employed as the internal standard in the GC-NICI-MS analysis. The limits of quantitation of tegafur, 5-fluorouracil, 5-chloro-2,4-dihydroxypyridine and potassium oxonate in plasma were 10, 1, 2 and 1 ng/ml, respectively. The reproducibility of the analytical method according to the statistical coefficients is approximately 10%. The accuracy of the method is good; that is, the relative error is < 10%. The methods were applied to pharmacokinetic studies of S-1 in patients.
Antineoplastic Combined Chemotherapy Protocols↗
Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET.
Schizophrenia is believed to involve altered activation of dopamine receptors, and support for this hypothesis comes from the antipsychotic effect of antagonists of the dopamine D2 receptor (D2R). D2R is expressed most highly in the striatum, but most of the recent positron emission tomography (PET) studies have failed to show any change in D2R densities in the striatum of schizophrenics, raising the possibility that other receptors may also be involved. In particular, the dopamine D1 receptor (D1R), which is highly expressed in the prefrontal cortex, has been implicated in the control of working memory, and working memory dysfunction is a prominent feature of schizophrenia. We have therefore used PET to examine the distribution of D1R and D2R in brains of drug-naive or drug-free schizophrenic patients. Although no differences were observed in the striatum relative to control subjects, binding of radioligand to D1R was reduced in the prefrontal cortex of schizophrenics. This reduction was related to the severity of the negative symptoms (for instance, emotional withdrawal) and to poor performance in the Wisconsin Card Sorting Test. We propose that dysfunction of D1R signalling in the prefrontal cortex may contribute to the negative symptoms and cognitive deficits seen in schizophrenia.
Adult↗
Comparative pharmacodynamic analysis of TAT-59 and tamoxifen in rats bearing DMBA-induced mammary carcinoma.
TAT-59 suppressed the growth of DMBA-induced mammary tumors in rats earlier and more strongly than tamoxifen (TAM). After oral administration of the drugs, DP-TAT-59, one of the main metabolites of TAT-59, was found in 10- to 15-fold higher concentrations in both the tumor and blood compared to 4-OH-TAM, an active metabolite of TAM. In a 3-day antiuterotrophic test, every detected metabolite of TAT-59 showed stronger antiestrogenic activity than did TAM. In a competition assay, the affinity of the metabolites for estrogen receptors ranged from that of estradiol to that of TAM. These results suggest that the superior antiestrogenic activity of TAT-59 compared to TAM was either due to its higher penetration into tumor tissue or to the stronger antiestrogenic activity of its metabolites.
9,10-Dimethyl-1,2-benzanthracene↗
Behavioral and neuroimaging studies on schizophrenia in Japan.
Chronic methamphetamine psychotics became a major problem in Japan after World War II. On one hand, the clinical symptoms of chronic methamphetamine psychotics were noted to resemble those of schizophrenics quite closely but, on the other hand, their respective personality profiles appeared to differ. Recent research on exploratory eye movements has also shown such similarities and differences. In long-term remitted chronic methamphetamine psychotics, extremely small doses of drugs, or stress, can be enough to cause a recurrence of symptoms. This phenomenon resembles the recurrence of schizophrenia, and animal experiments and basic research are being actively conducted in order to elucidate the mechanism involved. Some 20 years ago, unique studies were conducted that objectively looked at the characteristic behavior of severe chronic schizophrenics in a playground situation. Exploratory eye movements can also be regarded as a kind of behavior and, in this paper, eye movement patterns made in response to a maze test are discussed. In addition, much research on brain imaging in schizophrenia is being conducted in Japan and several interesting studies have also been chosen by the authors for presentation in this paper.
Brain↗
[Electroconvulsive therapy of affective disorders].
Compared with Europe and North America, fewer psychiatrists in Japan use electroconvulsive therapy (ECT) when treating affective disorders. We reviewed 25 papers focusing on this Modern ECT is a safe treatment, even in patients with severe systemic disabilities, as well as, in those who may be intolerant of tricyclic antidepressants. Modern ECT is considered to be as effective as or even more effective than antidepressant therapy. These facts indicate that Japanese psychiatrists should reconsider the application of ECT for treating affective disorders. In addition, knowledge derived from the study of ECT, can lead to a better understanding of the pathogenesis of depression and permit the design of more effective pharmacologic treatments.
Electroconvulsive Therapy↗
[Refractory depression].
It is generally accepted that antidepressants are ineffective in as many as 20 to 30 percent of patients with major depression. In Japan, the term "refractory" is commonly used to refer to a patient who does not respond to adequate treatment for depression, mainly standard pharmacotherapy. Factors associated with refractory depression are multiple. Refractory depression can be divided into several states, such as slightly depressive, neurotic, and residual. A variety of approaches to the refractory patient, that is pharmacotherapy, somatic therapy and psychotherapy is presented.
Antidepressive Agents↗
Classification of the clinical course of delusional and/or hallucinatory states in epilepsy.
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Adult↗
Determination of bisaramil and its metabolite in plasma using high-performance liquid chromatography with electrochemical detection.
A column liquid chromatographic method using electrochemical detection has been developed for determination of an antiarrhythmic agent, bisaramil, and its metabolite in plasma. The plasma was fractionated by extraction with chloroform and chloroform-ethanol, and each fraction was dried and dissolved in ethyl acetate. After back-extraction into an acidic buffer, bisaramil was chromatographed on a reversed-phase column, and the metabolite, which has a higher polarity, was analysed by ion-pairing chromatography. Calibration curves were linear over the concentration range 2-200 ng/ml with coefficients of variation, within-day or day-to-day, not exceeding 5% at any level. The limits of detection of bisaramil and its metabolite were 0.5 and 1 ng/ml, respectively, using 0.5 ml of plasma. The dual-electrode detector was operated in the screening mode of oxidation (electrode 1, +0.55 V; electrode 2, +0.8 V), providing a greater specificity and reducing the background noise. This procedure was applied to a large number of samples in a pharmacokinetic study at the therapeutic dose.
Anti-Arrhythmia Agents↗
Exploratory eye movements in schizophrenic patients and patients with frontal lobe lesions.
Exploratory eye movements in 20 schizophrenics, 18 patients with frontal lobe lesions (9 right-sided and 9 left-sided) and 20 normal controls were examined with an eye mark recorder while they viewed stationary S-shaped figures. The eye movements made during the subject's first 15-s viewing of an original figure were analyzed. Patients with right frontal lobe lesions (RF) and schizophrenics (S) had lower scores than normal controls (NC) for the number of eye fixations, total eye scanning length and mean eye scanning length. Each subject was then shown two other figures slightly different from the original and was requested to compare them with the original. After comparing them, the subject was asked the question, "Are there any other differences?" The eye movements made over the ensuing 5 s in response to this question were scored using the responsive search score (RSS). The RSS was low only in the S group. The subject was also asked to reproduce the original figure before and after making comparisons between the figures. The RF and S groups were poorer at reproduction than the NC group. These findings suggest that there is disordered function of the right frontal lobe in schizophrenia, and that schizophrenia is due not only to localized damage to one part of the brain but to more widespread damage.
Adult↗
Exploratory eye movements and neuropsychological tests in schizophrenic patients.
Exploratory eye movements in schizophrenic and nonschizophrenic subjects were examined with an eye mark recorder while the subjects viewed geometric figures. Elementary components of eye movements and the responsive search score (RSS), a function of the number of sections on which the subjects fixated, were measured by means of an eye movement analyzer and slow motion replay. The schizophrenic group and the depressed patient group had fewer eye fixations than the normal control group and the obsessive-compulsive disorder group. The schizophrenic group had a lower RSS average than patients with depression, patients with obsessive-compulsive disorders, or subjects in the normal control group. These results in conjunction with those of our previous studies suggest that a low RSS is specific to schizophrenia. We examined the relationship between these eye movements and neuropsychological tests and also investigated the relation between the eye movements and clinical symptoms by means of the Brief Psychiatric Rating Scale, Schedule for Affective Disorders and Schizophrenia, and the Scale for the Assessment of Negative Symptoms. The RSS correlated positively with the performance IQ and Wechsler's Maze test, but not with the Wisconsin Card Sorting Test or the verbal IQ result. The RSS also correlated negatively with negative symptoms. These results suggest that the RSS has two characteristic features: it is strongly associated with the interpersonal response and it may be connected with visuospatial and visuomotor functions including attention.
Adult↗
WHO project on eye movements in patients with schizophrenia.
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Cross-Cultural Comparison↗
Decreased superoxide dismutase activity in erythrocyte in Parkinson's disease.
Superoxide dismutase (SOD) activities in Parkinson's disease (PD) were significantly lower than those in controls, especially in a treated PD group. However, SOD activities in an untreated PD group did not decrease. There was a significant correlation between SOD activities and the duration of illness in the treated PD group (p < 0.05). There was a significant correlation between SOD activities and the present doses of L-DOPA/carbidopa in the treated PD group.
Aged↗
Eye movements in acute, chronic, and remitted schizophrenics.
Eye movements in 10 acute schizophrenics, 50 chronic schizophrenics, 20 remitted schizophrenics, 25 methamphetamine psychotics, 21 temporal lobe epileptics with left-sided spike focus (l-focus), 12 temporal lobe epileptics with right-sided spike focus (r-focus), and 50 normal controls were examined with an eye mark recorder while they viewed geometric figures. The eye movements while viewing an original "S"-shaped figure for 15 sec were analyzed. Each schizophrenic group and methamphetamine psychotics had significantly less eye fixations than the normal controls and temporal lobe epileptics (r-focus and l-focus). The chronic schizophrenics had significantly shorter mean eye scanning length (MESL) than the other six groups. Each subject was then shown two other figures slightly different from the original and was requested to compare them with the original. After comparing them, the subjects were asked the question, "Are there any other differences?" The 5-sec eye movements during the response to this question were scored using the Responsive Search Score (RSS). The schizophrenic groups had a significantly lower RSS than the nonschizophrenic patient groups and the normal controls. In the chronic schizophrenics, there was a significant negative correlation between the RSS and negative symptoms. These results suggest that the MESL can be an indicator of a chronic process of schizophrenia, and that lowering of the RSS may be a nosologically specific indicator for schizophrenia.
Acute Disease↗
The threshold of pain and neurotransmitter's change on pain in Parkinson's disease.
Among Parkinson's disease (PD) patients complaining of pain, 10 with pain not associated with a motor fluctuation or L-dopa therapy were evaluated. The controls were 14 PD without pain and eight with thalamic pain syndrome. The threshold of pain and neurotransmitters in CSF were measured in the three groups. In PD with pain, the maximum tolerance level and tourniquet pain ratio decreased significantly. In PD with pain, the score on the self-depression scale increased significantly and 5-hydroxy-indole acetic acid (5-HIAA) among the neurotransmitters decreased significantly. These results suggest that decreases in the threshold of pain and changes of serotonin in CSF are involved in the development of specific pain in PD who do not respond to L-dopa.
Aged↗
Limited eye movement patterns in chronic schizophrenic patients.
Eye movements of 29 chronic schizophrenic patients and 23 normal control subjects were measured by an eye mark recorder during viewing of stationary geometric figures. The results suggested that the eye movements of schizophrenic patients were more limited than those of normal control subjects and that the abnormal eye movement inspection patterns in schizophrenic patients may reflect a lack of visual investigation of novel stimuli in the environment. Our findings, together with Moriya's (1979) observation of similar eye movement pattern abnormalities in the relatives of schizophrenic patients, support the hypothesis that the limited eye movement patterns may be a biological marker for schizophrenia.
Adult↗
Gas chromatographic-negative-ion chemical ionization mass spectrometric determination of a new dihydropyridine calcium antagonist (MPC-1304) and its metabolites in human plasma and urine.
A gas chromatographic-negative-ion chemical ionization mass spectrometric method was developed for the determination of a new calcium antagonist, (+/-)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, and its metabolites in plasma and urine. The sample was extracted with n-hexane-diethyl ether. The dried organic layer was subjected to acetylation: the aqueous layer was acidified and extracted with ethyl acetate, and after the ethyl acetate extract was dried the resulting residue was subjected to methylation. Aliquots of each reactant solution were injected into the gas chromatograph-mass spectrometer, equipped with a chemical ionization source and negative-ion monitoring mode, and analysed by the selected-ion monitoring method using deuterium-labelled internal standards. Detection was limited to 0.02-0.05 ng/ml of plasma and urine for each metabolite. A precise and sensitive assay for the determination of a new dihydropyridine calcium antagonist and its metabolites in plasma and urine was thus established.
Animals↗