RESUMEN
Objective: Cognitive impairment after intensive care unit (ICU) admission is becoming increasingly recognized. High-dose deep sedation has been suggested to play an important role in the development of cognitive impairment. However, the impact of heavy sedation as a single cause in the development of cognitive impairment in ICU patients remains unclear. In this study we investigated whether a three-day deep sedation protocol could reduce cognitive function in mechanically ventilated non-critical patients. Design: A prospective observational study was carried out. Patients: A total of 17 surgical patients were studied. Intervention: None. Variables of interest: Cognitive function before and after ICU admission. Results: Thirty-one patients requiring three days of sedation after microvascular reconstruction were initially enrolled in the study. Sedation in the ICU was maintained with propofol and dexmedetomidine combined with fentanyl. Cognitive function was assessed using a battery of 6 neuropsychological tests two days before surgery and three weeks after surgery. Finally, a total of 17 patients were included in the analysis. Cognitive impairment (defined as a decline of >20% from the pre-admission cognitive evaluation scores in at least two of 6 tests) was observed in 5 of the 17 patients (29%). However, there were no significant differences between the pre- and post-admission cognitive evaluations in 6 tests. Conclusions: Middle-term cognitive function can be impaired in some patients subjected to deep sedation during several days following maxillary-mandibular oral surgery with microvascular reconstruction
Objetivo: Cada vez existe un mayor consenso sobre la afectación cognitiva tras el ingreso en la unidad de cuidados intensivos (UCI). Se ha sugerido que la sedación profunda con dosis elevada desempeña un papel importante en el desarrollo de la alteración cognitiva. Sin embargo, todavía existen dudas sobre el impacto de este tipo de sedación como causa única del desarrollo de alteraciones cognitivas en pacientes ingresados en la UCI. En este estudio, investigamos si la aplicación de un protocolo de sedación profunda durante 3 días disminuía la función cognitiva en pacientes no críticos bajo ventilación mecánica. Diseño: Se llevó a cabo un estudio observacional prospectivo. Pacientes: Se estudió a un total de 17 pacientes quirúrgicos. Intervenciones: Ninguna. Variables de interés: Función cognitiva antes y después del ingreso en la UCI. Resultados: En este estudio se incluyó inicialmente a 31 pacientes que requerían 3 días de sedación tras una reconstrucción microvascular. Se mantuvo la sedación en la UCI con propofol y dexmedetomidina en combinación con fentanilo. Se evaluó la función cognitiva mediante un grupo de 6 pruebas neurofisiológicas antes de la intervención y 3 días después de esta. Por último, se incluyó a un total de 17 pacientes en el análisis. Se observó alteración cognitiva (definida como una reducción>20% frente a las puntuaciones de la evaluación cognitiva previa al ingreso en al menos 2 de las 6 pruebas) en 5 de los 17 pacientes (29%). Sin embargo, no se observaron diferencias significativas entre las evaluaciones previas y posteriores al ingreso en 6 pruebas. Conclusiones: La función cognitiva a medio plazo puede verse afectada en algunos pacientes sometidos a sedación profunda durante varios días tras una cirugía oral maxilar-mandibular con reconstrucción microvascular
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Sedación Profunda/efectos adversos , Respiración Artificial , Procedimientos Quirúrgicos Orales , Cuidados Críticos , Disfunción Cognitiva/inducido químicamente , Estudios Prospectivos , Unidades de Cuidados Intensivos , Neurofisiología , Periodo Posoperatorio , Sedación Profunda/métodos , Cognición/efectos de los fármacosRESUMEN
OBJECTIVE: Cognitive impairment after intensive care unit (ICU) admission is becoming increasingly recognized. High-dose deep sedation has been suggested to play an important role in the development of cognitive impairment. However, the impact of heavy sedation as a single cause in the development of cognitive impairment in ICU patients remains unclear. In this study we investigated whether a three-day deep sedation protocol could reduce cognitive function in mechanically ventilated non-critical patients. DESIGN: A prospective observational study was carried out. PATIENTS: A total of 17 surgical patients were studied. INTERVENTION: None. VARIABLES OF INTEREST: Cognitive function before and after ICU admission. RESULTS: Thirty-one patients requiring three days of sedation after microvascular reconstruction were initially enrolled in the study. Sedation in the ICU was maintained with propofol and dexmedetomidine combined with fentanyl. Cognitive function was assessed using a battery of 6 neuropsychological tests two days before surgery and three weeks after surgery. Finally, a total of 17 patients were included in the analysis. Cognitive impairment (defined as a decline of >20% from the pre-admission cognitive evaluation scores in at least two of 6 tests) was observed in 5 of the 17 patients (29%). However, there were no significant differences between the pre- and post-admission cognitive evaluations in 6 tests. CONCLUSIONS: Middle-term cognitive function can be impaired in some patients subjected to deep sedation during several days following maxillary-mandibular oral surgery with microvascular reconstruction.
Asunto(s)
Trastornos del Conocimiento/prevención & control , Cognición/efectos de los fármacos , Cuidados Críticos , Sedación Profunda/efectos adversos , Complicaciones Posoperatorias/prevención & control , Respiración Artificial , Anciano , Anciano de 80 o más Años , Protocolos Clínicos , Trastornos del Conocimiento/inducido químicamente , Dexmedetomidina , Neoplasias Faciales/cirugía , Femenino , Fentanilo , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Unidades de Cuidados Intensivos , Masculino , Neoplasias Maxilares/cirugía , Microcirculación , Persona de Mediana Edad , Neoplasias de la Boca/cirugía , Pruebas Neuropsicológicas , Complicaciones Posoperatorias/inducido químicamente , Propofol , Estudios Prospectivos , Procedimientos de Cirugía Plástica , Factores de TiempoRESUMEN
BACKGROUND: Exposure of the developing brain to propofol results in cognitive deficits. Recent data suggest that inhibition of neuronal apoptosis does not prevent cognitive defects, suggesting mechanisms other than neuronal apoptosis play a role in anaesthetic neurotoxicity. Proper neuronal growth during development is dependent upon growth cone morphology and axonal transport. Propofol modulates actin dynamics in developing neurones, causes RhoA-dependent depolymerisation of actin, and reduces dendritic spines and synapses. We hypothesised that RhoA inhibition prevents synaptic loss and subsequent cognitive deficits. The present study tested whether RhoA inhibition with the botulinum toxin C3 (TAT-C3) prevents propofol-induced synapse and neurite loss, and preserves cognitive function. METHODS: RhoA activation, growth cone morphology, and axonal transport were measured in neonatal rat neurones (5-7 days in vitro) exposed to propofol. Synapse counts (electron microscopy), dendritic arborisation (Golgi-Cox), and network connectivity were measured in mice (age 28 days) previously exposed to propofol at postnatal day 5-7. Memory was assessed in adult mice (age 3 months) previously exposed to propofol at postnatal day 5-7. RESULTS: Propofol increased RhoA activation, collapsed growth cones, and impaired retrograde axonal transport of quantum dot-labelled brain-derived neurotrophic factor, all of which were prevented with TAT-C3. Adult mice previously treated with propofol had decreased numbers of total hippocampal synapses and presynaptic vesicles, reduced hippocampal dendritic arborisation, and infrapyramidal mossy fibres. These mice also exhibited decreased hippocampal-dependent contextual fear memory recall. All anatomical and behavioural changes were prevented with TAT-C3 pre-treatment. CONCLUSION: Inhibition of RhoA prevents propofol-mediated hippocampal neurotoxicity and associated cognitive deficits.
Asunto(s)
Transporte Axonal/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Conos de Crecimiento/efectos de los fármacos , Propofol , Sinapsis/efectos de los fármacos , Proteína de Unión al GTP rhoA/antagonistas & inhibidores , Animales , Toxinas Botulínicas , Encéfalo/efectos de los fármacos , Modelos Animales de Enfermedad , Hipnóticos y Sedantes , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Síndromes de Neurotoxicidad , Ratas , Ratas Sprague-Dawley , Proteína de Unión al GTP rhoA/genéticaRESUMEN
CX3CR1, a G protein-coupled receptor solely expressed by microglia in the brain, has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in transcriptomic and animal studies but not in genetic studies. To address the impacts of variants in CX3CR1 on neurodevelopmental disorders, we conducted coding exon-targeted resequencing of CX3CR1 in 370 Japanese SCZ and 192 ASD patients using next-generation sequencing technology, followed by a genetic association study in a sample comprising 7054 unrelated individuals (2653 SCZ, 574 ASD and 3827 controls). We then performed in silico three-dimensional (3D) structural modeling and in vivo disruption of Akt phosphorylation to determine the impact of the detected variant on CX3CR1-dependent signal transduction. We detected a statistically significant association between the variant Ala55Thr in CX3CR1 with SCZ and ASD phenotypes (odds ratio=8.3, P=0.020). A 3D structural model indicated that Ala55Thr could destabilize the conformation of the CX3CR1 helix 8 and affect its interaction with a heterotrimeric G protein. In vitro functional analysis showed that the CX3CR1-Ala55Thr mutation inhibited cell signaling induced by fractalkine, the ligand for CX3CR1. The combined data suggested that the variant Ala55Thr in CX3CR1 might result in the disruption of CX3CR1 signaling. Our results strengthen the association between microglia-specific genes and neurodevelopmental disorders.
Asunto(s)
Trastorno del Espectro Autista/genética , Receptor 1 de Quimiocinas CX3C/genética , Esquizofrenia/genética , Adolescente , Adulto , Anciano , Niño , Simulación por Computador , Exones , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
The analgesic effect of porcine calcitonin (PCT) was studied in 32 patients with cancer-induced bone destruction. Twenty patients (62.5%) showed some response among them 10 of 13 patients who had suffered from uncontrollable pain despite other treatment methods such as radiotherapy, and or the administration of other analgesics. The effect was observed about 10 days after the administration of the drug. Combined therapy with PCT and other modalities such as radiotherapy, chemotherapy and hormone therapy had a marked effect in controlling the pain.
Asunto(s)
Neoplasias Óseas/fisiopatología , Calcitonina/uso terapéutico , Dolor Intratable/tratamiento farmacológico , Adolescente , Adulto , Anciano , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Neoplasias de la Mama/fisiopatología , Calcitonina/efectos adversos , Niño , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Neoplasias del Recto/patología , Neoplasias del Recto/fisiopatología , Vómitos/inducido químicamenteRESUMEN
T-1982 (cefbuperazone), a new cephamycin antibiotic, was fundamentally and clinically studied in the field of obstetrics and gynecology. The following results were obtained. The concentrations of T-1982 in arterial and venous blood and genitalia following intravenous injection were measured. The results demonstrated favourable transfer of the drug into various internal genital organs. T-1982 was administered to 12 patients. The efficacy rate was 75.0%, that is to say, good in 9 cases. No side effects were noted in any cases. It is, therefore, presumed that T-1982 is a useful drug for the infectious diseases in the field of obstetrics and gynecology although the number of subjects was not so large in this study.
Asunto(s)
Cefamicinas/metabolismo , Adulto , Cefamicinas/uso terapéutico , Endometritis/tratamiento farmacológico , Endometritis/microbiología , Enterococcus faecalis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Femenino , Humanos , Persona de Mediana Edad , Ovario/metabolismo , Enfermedad Inflamatoria Pélvica/tratamiento farmacológico , Útero/metabolismoRESUMEN
Applications of hyperthermia in cancer therapy is now widely studied. Appropriate apparatus for the tumors with various size and positions should be developed. We are developing a system with 2450 MHz microwave and constructed several applicators for the surface tumors and intracavitary tumors. Those were already used in human tumors. Capacitive heating with RF were used for the combined therapy with radiation in Kyoto University. More than 50% of the treated cases were responded well resulting complete regression of tumors. Experimental system of heating with magnetic induction is now studied.
Asunto(s)
Calor/uso terapéutico , Anciano , Neoplasias de la Mama/patología , Femenino , Humanos , Microondas/uso terapéutico , Neoplasias Cutáneas/secundario , Neoplasias Cutáneas/terapia , Terapia por Ultrasonido , Neoplasias del Cuello Uterino/terapiaRESUMEN
A clinical trial of radiation therapy combined with hyperthermia for various superficial tumors was performed. For the local hyperthermia, heating modalities with microwave, radiofrequency and ultrasound can be used. Some are still insufficient for clinical application in terms of tumor size and site; there fore, for ther studies through a phase II study are necessary to determine a future direction of hyperthermia in clinical case.
Asunto(s)
Calor/uso terapéutico , Neoplasias/terapia , Femenino , Neoplasias de Cabeza y Cuello/terapia , Humanos , Microondas/uso terapéutico , Neoplasias/radioterapia , Neoplasias Cutáneas/terapia , Terapia por Ultrasonido , Neoplasias del Cuello Uterino/terapiaAsunto(s)
Boro , Neoplasias Encefálicas/radioterapia , Compuestos de Litio , Neutrones , Monitoreo de Radiación , Boratos , Fluoruros , Humanos , LitioAsunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Cefalosporinas/uso terapéutico , Enfermedades de los Genitales Femeninos/tratamiento farmacológico , Preeclampsia/tratamiento farmacológico , Adulto , Cefoperazona , Cefalosporinas/administración & dosificación , Cefalosporinas/metabolismo , Evaluación de Medicamentos , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
The effect of irradiation and chemotherapeutic agents on the capillaries of experimental solid tumours was analysed by the resin cast method. The most evident change of the 5 vascular layers was rarefaction of the newly produced extruding capillaries on the surface of the tumour mass, which was related to the tumour growth.
Asunto(s)
Bleomicina/farmacología , Capilares/patología , Carcinoma de Ehrlich , Fluorouracilo/farmacología , Animales , Bleomicina/administración & dosificación , Capilares/efectos de los fármacos , Capilares/efectos de la radiación , Carcinoma de Ehrlich/irrigación sanguínea , Carcinoma de Ehrlich/tratamiento farmacológico , Carcinoma de Ehrlich/radioterapia , Radioisótopos de Cobalto , Femenino , Fluorouracilo/administración & dosificación , Inyecciones Intraperitoneales , Masculino , Ratones , Trasplante de Neoplasias , Factores de Tiempo , Trasplante HomólogoRESUMEN
The vascular structure of experimental tumours was investigated by a resin cast technique. Six characteristic types of capillaries were found: club-like, wave-like, tortuous,sinusoid-like, disorderly running and tapering. The vascular structure was correlated to the tumour growth.