RESUMEN
The Psychiatric Board System under the Japanese Society of Psychiatry and Neurology was started in 2004. Over the last 10 years, psychiatrists who had worked in the field of psy- chiatry and were recognized as having the necessary training took the board examination, and 10,498 psychiatrists acquired the Psychiatric Specialty Board certification. On the other hand, new psychiatrists who trained according to a special curriculum for more than 3 years took the board examination, and 762 psychiatrists obtained certification through the Psychiatric Specialty Board. According to principle of this system, the Psychiatric Board System should resolve several issues, such as the kind of training facility, issues with medical teaching staff and training pro- grams, the examination system, and the renewal system. An outline of the New Board System under the Japanese Medical Specialty Board is pro- vided, and this system is expected to improve the Psychiatric Board System and may promote the quality of psychiatrists.
Asunto(s)
Educación Médica , Sociedades Médicas , Japón , Neurología/educación , Psiquiatría/educación , Consejos de EspecialidadesRESUMEN
This prospective, nationwide, specified drug use-results survey investigated the effects of levetiracetam (LEV) in elderly individuals with partial-onset seizures of advanced-age onset in a practical setting. Participants comprised LEV-naïve patients with onset of focal epilepsy at ≥50 years old and management by at least one antiepileptic drug. Efficacy measures were the physician-rated global improvement scale (GIS), and proportions of patients showing 50% and 100% seizure reduction by comparing seizure frequency during the 4-week pre-treatment period and the last 4 weeks of the 25-week treatment period. Adverse drug reactions (ADRs) and retention rate were also evaluated. Data for safety, GIS evaluation, and seizure frequency analyses were available from 105, 78, and 76, respectively, of 116 enrolled patients, 83 (71.55%) of whom were enrolled by neurosurgeons. Improvement rate (improved or markedly improved) as determined by GIS was 98.72% (77/78). Seventy-four (97.37%) and 64 patients (84.21%) showed 50% and 100% seizure reduction, respectively. Incidence of ADRs was 12.38%, including one serious ADR (mania). LEV retention rate remained high at the end of the 25-week treatment period (96.00%). LEV appears efficacious and well-tolerated in elderly patients with focal epilepsy. Including LEV in the treatment regimen may allow elderly patients to achieve freedom from seizures.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsias Parciales/tratamiento farmacológico , Piracetam/análogos & derivados , Anciano , Anticonvulsivantes/efectos adversos , Recolección de Datos , Quimioterapia Combinada , Femenino , Humanos , Levetiracetam , Masculino , Persona de Mediana Edad , Piracetam/efectos adversos , Piracetam/uso terapéutico , Estudios ProspectivosAsunto(s)
Crecimiento y Desarrollo/fisiología , Convulsiones/etiología , Convulsiones/fisiopatología , Potenciales de Acción , Animales , Encéfalo/citología , Encéfalo/fisiología , Modelos Animales de Enfermedad , Geles , Vías Nerviosas/fisiología , Neuronas/fisiología , Penicilinas , Transmisión Sináptica/fisiología , Compuestos de TungstenoRESUMEN
This double-blind study was conducted to evaluate the efficacy and safety of gabapentin 1200 mg/day and 1800 mg/day (t.i.d.) compared to placebo as an adjunctive therapy in patients with refractory epilepsy. Patients were included when they had partial seizures at least eight times during a 12-week baseline period despite treatment with one to two antiepileptic drugs. After baseline, eligible patients were randomized to gabapentin 1200 mg/day, 1800 mg/day, or placebo for 12-week treatment. The primary end-point, response ratio, was derived from seizure frequencies during treatment and baseline period based upon the seizure daily record by a patient. Of the 209 randomized patients, 86 received gabapentin 1200 mg/day, 41 received gabapentin 1800 mg/day, and 82 received placebo. A statistically significant difference was found between each of the two gabapentin groups and placebo for the primary efficacy end-point, response ratio (P < 0.005) with definite dose-response (P < 0.001). More gabapentin patients reported moderate to marked improvement in seizure frequency and intensity/duration of each seizure than placebo patients. Treatment-related adverse events were reported by approximately 65% of patients receiving gabapentin compared to approximately 46% of patients receiving placebo; somnolence and dizziness were the most common events. Gabapentin 1200 mg/day and 1800 mg/day significantly reduced the frequency of refractory seizures compared to placebo. Favorable tolerability of gabapentin was confirmed also in a Japanese population, consistent with previous global studies.
Asunto(s)
Aminas/uso terapéutico , Anticonvulsivantes/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Epilepsias Parciales/tratamiento farmacológico , Ácido gamma-Aminobutírico/uso terapéutico , Adolescente , Adulto , Anciano , Aminas/efectos adversos , Anticonvulsivantes/efectos adversos , Ácidos Ciclohexanocarboxílicos/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Gabapentina , Humanos , Japón , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Ácido gamma-Aminobutírico/efectos adversosRESUMEN
PURPOSE: Nefiracetam (NEF) is a novel pyrrolidonetype nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition-enhancing effects. The present study focused on the effects of NEF in amygdala-kindled seizures and its potential for antiepileptic therapy. METHODS: Effects of NEF on fully amygdala-kindled seizures and development of amygdala-kindled seizures were investigated in rats and compared with those of levetiracetam (LEV), a pyrrolidone-type antiepileptic drug (AED). RESULTS: In fully amygdala-kindled rats, NEF (25, 50, and 100 mg/kg, p.o.) decreased afterdischarge induction, afterdischarge duration, seizure stage, and motor seizure duration in a dose-dependent manner. LEV (25, 50, and 100 mg/kg, p.o.) had no effects on afterdischarge induction and slightly decreased afterdischarge duration, whereas it markedly decreased seizure stage and motor seizure duration. In contrast to the results in fully amygdala-kindled rats, NEF (25 and 50 mg/kg/day, p.o.) had few or no effects on the development of amygdala-kindled seizures. As well as fully amygdala-kindled seizures, LEV (50 mg/kg/day, p.o.) markedly inhibited the development of behavioral seizures without reducing daily afterdischarge duration. CONCLUSIONS: Although NEF possesses potent anticonvulsant effects on fully amygdala-kindled seizures, it has few or no effects on the development of amygdala-kindled seizures. LEV shows marked anticonvulsant effects on both phases of kindling. In fully amygdala-kindled rats, NEF inhibits both electroencephalographic and behavioral seizures, whereas LEV inhibits only behavioral seizures. This double dissociation suggests that NEF has a distinct anticonvulsant spectrum and mechanisms from those of LEV.
Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Anticonvulsivantes/farmacología , Excitación Neurológica/efectos de los fármacos , Nootrópicos/farmacología , Pirrolidinonas/farmacología , Convulsiones/prevención & control , Administración Oral , Amígdala del Cerebelo/fisiopatología , Animales , Anticonvulsivantes/uso terapéutico , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Estimulación Eléctrica , Electrodos Implantados , Electroencefalografía/estadística & datos numéricos , Epilepsia Parcial Compleja/tratamiento farmacológico , Humanos , Excitación Neurológica/fisiología , Levetiracetam , Masculino , Nootrópicos/uso terapéutico , Piracetam/administración & dosificación , Piracetam/análogos & derivados , Piracetam/farmacología , Piracetam/uso terapéutico , Pirrolidinonas/administración & dosificación , Pirrolidinonas/uso terapéutico , Ratas , Ratas Wistar , Convulsiones/tratamiento farmacológico , Convulsiones/fisiopatologíaRESUMEN
Nefiracetam is a novel pyrrolidone-type nootropic agent, and it has been reported to possess a potential for antiepileptic therapy as well as cognition-enhancing effects. We investigated the anticonvulsant and neuroprotective effects of nefiracetam in kainic acid-induced seizures of rats, compared with levetiracetam and standard antiepileptic drugs. Subcutaneous injection of kainic acid (10 mg/kg) induced typical behavioral seizures such as wet dog shakes and limbic seizures and histopathological changes in the hippocampus (degeneration and loss of pyramidal cells in CA1 to CA4 areas). Nefiracetam (25, 50 and 100 mg/kg po) had no effect on the behavioral seizures and dose-dependently inhibited the hippocampal damage. In contrast, levetiracetam, a pyrrolidone-type antiepileptic drug, inhibited neither. Valproic acid and ethosuximide prevented the hippocampal damage without attenuating the behavioral seizures as nefiracetam. Zonisamide and phenytoin did not inhibit the behavioral seizures, while zonisamide enhanced the hippocampal damage and phenytoin increased the lethality rate. Carbamazepine inhibited the behavioral seizures at 50 mg/kg and enhanced that at 100 mg/kg, and it completely inhibited the hippocampal damage at both doses. We have previously reported that anticonvulsant spectrum of nefiracetam paralleled that of zonisamide, phenytoin or carbamazepine in standard screening models. However, the pharmacological profile of nefiracetam was closer to valproic acid or ethosuximide than that of zonisamide, phenytoin or carbamazepine in this study. These results suggest that anticonvulsant spectrum and mechanism of nefiracetam are distinct from those of standard antiepileptic drugs, and nefiracetam possesses a neuroprotective effect that is unrelated to seizure inhibition.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Ácido Kaínico , Fármacos Neuroprotectores/uso terapéutico , Pirrolidinonas/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Masculino , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Estadística como Asunto , Factores de TiempoRESUMEN
Trazodone is an effective antidepressant drug with a broad therapeutic spectrum, including anxiolytic efficacy. Although trazodone is usually referred to as a serotonin (5-HT) reuptake inhibitor, this pharmacological effect appears to be too weak to fully account for its clinical effectiveness. The present study aimed to elucidate the agonist properties of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP), at 5-HT(1A) receptors by means of the guanosine-5'-O-(3-[(35)S]thio)-triphosphate ([(35)S]GTPgammaS) binding assay. In membranes prepared from Chinese hamster ovary cells expressing human 5-HT(1A) receptors (CHO/h5-HT(1A)), trazodone behaved as an almost full agonist and m-CPP was also a highly efficacious partial agonist at 5-HT(1A) receptors. The intrinsic activities of both compounds were higher than those of tandospirone and buspirone, which are clinically effective anxiolytics with well-known 5-HT(1A) partial agonist properties. These effects were replicated in the 5-HT(1A) receptor-mediated [(35)S]GTPgamma(S) binding assay in native rat brain membranes (at least in hippocampal membranes), although the intrinsic activities of the compounds were low and differently ranked compared to those in CHO/h5-HT(1A) cell membranes. When considering the implications of 5-HT(1A) receptors in anxiety and/or depression, as well as the clinical effectiveness of azapirone anxiolytics with partial 5-HT(1A) receptor agonist properties such as buspirone, it is possible that the agonist effects on 5-HT(1A) receptors of trazodone and its active metabolite m-CPP presented in this study contribute, at least in part, to the clinical efficacy of the atypical antidepressant trazodone.
Asunto(s)
Antidepresivos de Segunda Generación/farmacología , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Piperazinas/farmacología , Receptor de Serotonina 5-HT1A/efectos de los fármacos , Agonistas de Receptores de Serotonina , Trazodona/farmacología , Animales , Células CHO , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Cricetinae , Relación Dosis-Respuesta a Droga , Proteínas de Unión al GTP/metabolismo , Técnicas In Vitro , Masculino , Ratas , Ratas Sprague-Dawley , Radioisótopos de AzufreRESUMEN
The current overview of zonisamide use and effectiveness is based on both a long-term prospective postmarketing survey and current zonisamide use at the Saitama Medical College, Department of Neuropsychiatry. Survey data, which were collected from individual physicians and 23 survey groups throughout Japan, assessed the effectiveness of zonisamide in 1631 patients. Zonisamide was highly effective for treating partial seizures, with 70% of patients reporting improvement. More than half of patients with generalized seizures (58%) and half of patients with myoclonic and atypical absence seizures showed improvement with zonisamide treatment. Among the different epileptic syndromes, zonisamide was highly effective in treating generalized idiopathic epilepsy (> or =78% improvement) and partial epilepsy (> or =58% improvement). However, only 28% of patients with West syndrome or Lennox-Gastaut syndrome showed improvement. Among 60 outpatients treated with zonisamide at our facility as of October 1998, most had partial seizures or generalized seizures subsequent to partial seizures. The majority of patients received zonisamide in combination with other antiepilepsy drugs. Patients receiving zonisamide monotherapy showed greater improvement than did patients receiving polytherapy. We conclude that zonisamide is highly effective for partial seizures and generalized seizures, and that there appears to be no decrease in efficacy with long-term use.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Isoxazoles/uso terapéutico , Vigilancia de Productos Comercializados , Adolescente , Adulto , Anticonvulsivantes/sangre , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Epilepsia/sangre , Epilepsia/clasificación , Epilepsia/epidemiología , Femenino , Humanos , Isoxazoles/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , ZonisamidaRESUMEN
The purpose of this study was to explore differences in mood profile evaluation between raters with different backgrounds. Special emphasis was placed on expertise factor, influence of mood categories, and patient heterogeneity in a clinical setting. We administered Profile of Mood Scale (POMS) to patients' families, residents, and experienced psychiatrists as well as the patients, asking them to make an evaluation based on their image of the patients' subjective mood experience. Subscale scores and within-case across-item agreement indices among the raters were submitted for analysis. Analysis of variance of the subscale score showed significant effects of the rater by subscale-category and the rater by case components. The former was most influenced by the Vigor/Activity subscale in which the families and patients had higher scores than the physicians. As for rater-to-patient correlations of the score, psychiatrists were superior to residents in Anger/Hostility and Fatigue/Inertia, while families were superior to physicians in Vigor/Activity. These results suggest significance of expertise in mood evaluation as well as importance of time shared with the patients. The within-case across-item agreement data were subjected to cluster and canonical discriminant analysis. The analysis revealed four clusters which were best explained by two dimensions, one interpreted as general feasibility of evaluation and the other as characteristic emotional expression which caused separation of evaluation between families and physicians. Rater's expertise is a significant factor. Attention should also be paid to mood categories and patient heterogeneity.
Asunto(s)
Cuidadores/psicología , Internado y Residencia , Trastornos del Humor/diagnóstico , Determinación de la Personalidad/estadística & datos numéricos , Competencia Profesional , Psiquiatría/educación , Análisis de Varianza , Humanos , Entrevista Psicológica , Cómputos Matemáticos , Trastornos Mentales/diagnóstico , Trastornos Mentales/psicología , Trastornos del Humor/psicología , Variaciones Dependientes del Observador , Psicometría/estadística & datos numéricos , Reproducibilidad de los ResultadosRESUMEN
Recent studies have shown that functional variations in clock genes, which generate circadian rhythms through interactive positive/negative feedback loops, contribute to the development of circadian rhythm sleep disorders in humans. Another potential candidate for rhythm disorder susceptibility is casein kinase I epsilon (CKIepsilon), which phosphorylates clock proteins and plays a pivotal role in the circadian clock. To determine whether variations in CKIepsilon induce vulnerability to human circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24), we analyzed all of the coding exons of the human CKIepsilon gene. One of the variants identified encoded an amino-acid substitution S408N, eliminating one of the putative autophosphorylation sites in the carboxyl-terminal extension of CKIepsilon. The N408 allele was less common in both DSPS (p = 0.028) and N-24 patients (p = 0.035) compared to controls. When DSPS and N-24 subjects were combined, based on an a priori prediction of a common mechanism underlying both DSPS and N-24, the inverse association between the N408 allele and rhythm disorders was highly significant (p = 0.0067, odds ratio = 0.42, 95% confidence interval: 0.22-0.79). In vitro kinase assay revealed that CKIepsilon with the S408N variation was approximately 1.8-fold more active than wild-type CKIepsilon. These results indicate that the N408 allele in CKIepsilon plays a protective role in the development of DSPS and N-24 through alteration of the enzyme activity.
Asunto(s)
Caseína Cinasa 1 épsilon/genética , Ritmo Circadiano/genética , Mutación Missense/genética , Trastornos del Sueño-Vigilia/genética , Adulto , Alelos , ADN Complementario/análisis , ADN Complementario/genética , Exones/genética , Femenino , Genotipo , Humanos , Intrones/genética , Cinética , Masculino , Fosforilación , Polimorfismo Conformacional Retorcido-Simple , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de RiesgoRESUMEN
According to DSM-IV criteria, gender identity disorder(GID) is characterized as follows: 1) Strong, persistent cross-gender identification. 2) Persistent discomfort with one's assigned sex or the Sense of inappropriateness in that gender role. 3) Not due to an intersex condition. In this chapter, symptoms, diagnosis and treatment of GID are briefly described. Possible pathogenesis of GID is also discussed.
Asunto(s)
Identidad de Género , Trastornos Sexuales y de Género , Encéfalo/patología , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Masculino , Psicoterapia , Caracteres Sexuales , Diferenciación Sexual , Trastornos Sexuales y de Género/diagnóstico , Trastornos Sexuales y de Género/etiología , Trastornos Sexuales y de Género/psicología , Trastornos Sexuales y de Género/terapia , Procedimientos Quirúrgicos UrogenitalesRESUMEN
gamma-Hydroxybutyric acid is a naturally occurring substance that may act as a neurotransmitter or neuromodulator to elicit several biological effects. Although the existence of a specific gamma-hydroxybutyric acid receptor has been postulated, the receptor protein itself has not been cloned yet. The current study was designed to elucidate whether gamma-hydroxybutyric acid receptors are functionally coupled with heterotrimeric G-proteins, especially Gi/Go family, by means of high-affinity GTPase activity and guanosine 5'-O-(3-[35S]thiotriphosphate) ([35S]GTPgammaS) binding assays in rat brain membranes. The stimulatory effects of GABAB receptor activation were always determined in parallel as a positive control. The selective GABAB receptor agonist (+/-)-baclofen stimulated the high-affinity GTPase activity in cerebral cortical, hippocampal, and striatal membranes, whereas gamma-hydroxybutyric acid was inactive up to 1 mM in these brain regions. The optimum assay conditions for [35S]GTPgammaS binding to detect a receptor-mediated activation of G-proteins at the greatest signal to noise ratio were then probed as to the concentrations of constituents in the assay mixture (GDP, MgCl2, and NaCl) and incubation period. Even under such an optimized experimental condition, [35S]GTPgammaS binding was not altered by gamma-hydroxybutyric acid in the membranes prepared from cerebral cortex or hippocampus. On the other hand, the specific [35S]GTPgammaS binding was increased by GABAB receptor agonists in a concentration-dependent manner, which was competitively inhibited by CGP54626, a selective GABAB receptor antagonist. These results indicate that gamma-hydroxybutyric acid receptors, if any, are not associated with G-proteins, at least Gi/Go family.
Asunto(s)
Encéfalo/efectos de los fármacos , Proteínas de Unión al GTP/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Hidroxibutiratos/farmacología , Receptores de Superficie Celular/efectos de los fármacos , Ácido gamma-Aminobutírico/farmacología , Animales , Baclofeno/farmacología , Encéfalo/enzimología , Encéfalo/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Agonistas del GABA/farmacología , Hidroxibutiratos/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Receptores de Superficie Celular/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
PURPOSE: Alternate-site kindling (AK), which has been known to induce so-called kindling antagonism, was performed in the bilateral hippocampi to reveal neural mechanisms underlying hippocampal kindling. METHODS: Ten adult rabbits were used. Daily kindling stimulation consisted of a 1- s train of 50 pulses (pulse duration, 1 ms) of 80 to 200 microA (base-to-peak), which was higher than the afterdischarge (AD) threshold. The concurrent alternating stimulations were delivered to the right and left hippocampus once every 24 h. RESULTS: All animals developed a stage 5 convulsion with a mean of 28.1 +/- 3.3 (mean +/- SEM) stimulations. The right and left hippocampus received 14.8 +/- 1.7 and 14.6 +/- 1.6 stimulations, respectively. Behavioral stages induced by stimulation of the right or left hippocampus evolved to generalized seizures along a similar course. Kindling antagonism was not observed. The two sides showed similar increases in AD duration, and similar chronologic changes in interictal discharge (IID) frequency. Simple A-type IID and complex types of IID appeared at higher rates, whereas simple B-type IID remained at a relatively low level. CONCLUSIONS: The present AK procedure did not induce kindling antagonism, but it induced progression of kindling manifestations. The origin of simple B-type IID is known to be in the contralateral side, and its intracellular counterpart corresponds to a sequence of small depolarization followed by large hyperpolarization, suggesting that plastic changes in the feed-forward inhibitory system play an important role in hippocampal kindling.
Asunto(s)
Epilepsia/etiología , Lateralidad Funcional/fisiología , Hipocampo/fisiología , Excitación Neurológica/fisiología , Animales , Ritmo Circadiano/fisiología , Modelos Animales de Enfermedad , Estimulación Eléctrica/métodos , Electroencefalografía/estadística & datos numéricos , Epilepsia/fisiopatología , Hipocampo/fisiopatología , Masculino , Modelos Neurológicos , Red Nerviosa/fisiología , Inhibición Neural/fisiología , Plasticidad Neuronal/fisiología , Conejos , Convulsiones/etiología , Convulsiones/fisiopatologíaRESUMEN
PURPOSE: The h current (Ih) is an inwardly mixed cationic conductance activated by membrane hyperpolarization and distributed predominantly in the apical dendrites of hippocampal pyramidal neurons. To verify a hypothesis that an anomalous hyperpolarization generates an abnormal excitation by way of Ih channels, we examined the effects of Ih blockers (CsCl and ZD7288) on electrically induced paroxysmal discharges (PADs). METHODS: Fifty-three adult male rabbits were used. We measured the PAD threshold elicited by stimulation to the apical dendritic layer of the hippocampal CA1 region before and after injecting 50 microl of each Ih blocker or saline extracellularly into the same region. RESULTS: In Ih blocker injection groups (n = 26), we obtained a significant increase in PAD threshold (1 mM CsCl: 163%, p < 0.01; 10 mM CsCl: 265%, p < 0.01; 100 mM CsCl: 199%, p < 0.01; 100 microM ZD7288: 192%, p < 0.05; 1 mM ZD7288: 246%, p < 0.05). Conversely, we did not obtain the increase in PAD threshold in a saline injection group (n = 10, 107%). The magnitude as well as duration of the effect had a tendency to depend on concentration of Ih blockers, although a saturated or declining tendency was observed with the 100 mM CsCl injection. CONCLUSIONS: We concluded that Ih channels might contribute to hippocampal epileptiform discharges in vivo. Our hypothesis for epileptogenesis demonstrated in the present experiment offers an idea to develop a new type of antiepileptic drug based on Ih blockers for the treatment of epileptic disorders refractory to current medications.