Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
1.
Cortex ; 137: 271-281, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33662691

RESUMEN

The insular cortex is considered an important region for feeling emotions through interoception. Most studies that report the role of the insula in integrating interoception and emotion have used neuroimaging techniques such as functional magnetic resonance imaging (fMRI); however, there are limited neuropsychological studies. The effects of insular lesions on emotion and interoception have not been suitably investigated. In this study, we examined the role of the insular cortex in cardiac interoception and recognizing emotions from facial expressions by comparing them pre- and post-operatively in patients with glial tumors or brain metastases associated with the insular lobe. Although no significant difference in interoceptive accuracy was observed between the two phases, there were significant associations between the changes in interoceptive accuracy and sensitivity to expressions of anger and happiness. An increased error rate in the heartbeat counting task in the post-operation phase was associated with a decreased accuracy in recognizing anger and happiness. Since most patients had left insula lesions, generalizability of the findings to patients with right lesions is a future subject. To the best of our knowledge, this is the first study to examine the change in interoception and emotion after insular resection in humans. The study results indicate that removal of the insula affects the recognition of emotions such as anger and happiness through interoceptive processing.


Asunto(s)
Interocepción , Corteza Cerebral/diagnóstico por imagen , Emociones , Expresión Facial , Humanos , Imagen por Resonancia Magnética
2.
Sci Rep ; 10(1): 9044, 2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493943

RESUMEN

We aimed to investigate clinical parameters that affected the results of navigated repetitive transcranial magnetic stimulation (nrTMS) language mapping by comparing the results of preoperative nrTMS language mapping with those of direct cortical stimulation (DCS) mapping. In the prospective, non-randomized study, patients had to meet all of the following inclusion criteria: the presence of left- or right-side brain tumors in the vicinity of or inside the areas anatomically associated with language functions; awake brain surgery scheduled; and age >18 years. Sixty one patients were enrolled, and this study included 42 low-grade gliomas and 19 high-grade gliomas (39 men, 22 women; mean age, 41.1 years, range 18-72 years). The tumor was located in the left and right hemisphere in 50 (82.0%) and 11 (18.0%) patients, respectively. In the 50 patients with left-side gliomas, nrTMS language mapping showed 81.6% sensitivity, 59.6% specificity, 78.5% positive predictive value, and 64.1% negative predictive value when compared with the respective DCS values for detecting language sites in all regions. We then investigated how some parameters, including age, tumor type, tumor volume, and the involvement of anatomical language-related regions, affected different subpopulations. Based on the receiver operating curve statistics, subgroup analysis showed that the non-involvement of language-related regions afforded significantly better the area under the curve (AUC) values (AUC = 0.81, 95% confidence interval (CI): 0.74-0.88) than the involvement of language-related regions (AUC = 0.58, 95% CI: 0.50-0.67; p < 0.0001). Our findings suggest that nrTMS language mapping could be a reliable method, particularly in obtaining responses for cases without tumor-involvement of classical perisylvian language areas.


Asunto(s)
Neoplasias Encefálicas/cirugía , Cuidados Preoperatorios/métodos , Estimulación Magnética Transcraneal/métodos , Adolescente , Adulto , Anciano , Mapeo Encefálico/métodos , Neoplasias Encefálicas/patología , Corteza Cerebral/fisiología , Femenino , Glioma/cirugía , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , Neuronavegación/métodos , Estudios Prospectivos , Sensibilidad y Especificidad , Vigilia/fisiología
3.
J Neurooncol ; 146(1): 195-205, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31853839

RESUMEN

PURPOSE: This study aimed to investigate the preoperative predictive factors affecting return to work in patients with gliomas in the left cerebral hemisphere undergoing awake surgery. METHODS: We retrospectively reviewed 50 consecutive glioma patients who underwent awake surgery from January 2012 to July 2017. Adult patients older than 18 years, who reported working prior to surgery, were recruited for this study. RESULTS: Comparing sociodemographic, disease-related and preoperative neurocognitive variables of glioma patients who returned to work and those who did not, binomial logistic regression models for preoperative predictors affecting return to work revealed significant differences in age and sole breadwinner status as sociodemographic variables, tumour volume as a disease-related variable, and Verbal IQ, Performance IQ, general memory, attention/concentration, and working memory as neurocognitive variables. Multivariate logistic regression models demonstrated that the independent factors associated with propriety of returning to work 1 year after surgery was the sociodemographic variable sole breadwinner status (yes vs no; OR = 15.00, 95% CI 2.22-101.35, p = 0.01), the disease-related variable tumour volume (per 1 cm3; OR = 0.98, 95% CI 0.96-0.99, p = 0.04), and the preoperative neurocognitive variable general memory (≥ 100 vs < 100; OR = 21.70, 95% CI 2.60-183.94, p = 0.01). CONCLUSIONS: Our results suggest that three predictive factors including sole breadwinner status, tumour volume and general memory that can be assessed in the preoperative stage substantially contribute to returning to work in patients with gliomas in the left cerebral hemisphere, 1 year after awake surgery.


Asunto(s)
Mapeo Encefálico/métodos , Neoplasias Encefálicas/cirugía , Craneotomía/métodos , Glioma/cirugía , Cuidados Preoperatorios , Indicadores de Calidad de la Atención de Salud , Reinserción al Trabajo/estadística & datos numéricos , Adulto , Anciano , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/psicología , Cognición , Femenino , Estudios de Seguimiento , Glioma/patología , Glioma/psicología , Humanos , Renta , Masculino , Memoria , Persona de Mediana Edad , Monitoreo Intraoperatorio , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Cambio Social , Carga Tumoral , Vigilia , Adulto Joven
4.
Brain Struct Funct ; 224(6): 2167-2181, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31168738

RESUMEN

With the objective to investigate the role of the insula in recognizing emotion, we performed direct electrical stimulation over the anterior insular cortex during awake surgery while simultaneously delivering an emotional sensitivity task. We registered 18 consecutive patients with brain tumors associated with the insular lobe, who were undergoing tumor resection. An emotional sensitivity task was employed to measure the patients' ability to recognize emotions from facial expressions before, during, and after awake surgery. Furthermore, we performed voxel-based lesion symptom mapping (VLSM) to identify the association between relevant brain lesions and emotion recognition. When we performed direct electrical stimulation over the anterior insular cortex during awake surgery, the results showed that the ability to recognize anger was significantly enhanced with the presence of anterior insular stimulation (p < 0.05). Comparing the performance in the emotional sensitivity task before and after surgery, the performance in the anger condition became worse (p < 0.01), but became better in the sadness condition after surgery (p < 0.01). In the case of anger recognition, lower scores in the correct response index were associated with lesions involving the left insula in the VLSM study. Direct electrical stimulation over the anterior insular cortex enhanced anger recognition in patients with insular tumors. In contrast, accuracy of anger recognition was significantly reduced, and sadness was improved, when the performance of emotional sensitivity was compared pre- and post-surgery. Our findings suggest that the insular cortex is involved in changes in emotion recognition, including anger and sadness recognition by modulating arousal level that is closely connected with interoception.


Asunto(s)
Neoplasias Encefálicas/patología , Emociones/fisiología , Reconocimiento Facial/fisiología , Reconocimiento Visual de Modelos/fisiología , Adolescente , Adulto , Anciano , Mapeo Encefálico/métodos , Neoplasias Encefálicas/fisiopatología , Corteza Cerebral/fisiopatología , Corteza Cerebral/cirugía , Expresión Facial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Vigilia/fisiología , Adulto Joven
5.
World Neurosurg ; 129: 283-286, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31229747

RESUMEN

BACKGROUND: Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSAH) is a well-described subset of subarachnoid hemorrhage with an excellent prognosis in adults. However, its characteristics in the pediatric population have not yet been fully understood. We present a case of acute hydrocephalus requiring external ventricular drainage following pediatric PNSAH. CASE DESCRIPTION: A previously healthy 10-year-old girl was admitted to our neurosurgical department after sudden onset of severe headache with vomiting during exercise. Cerebral non-contrast computed tomography detected subarachnoid hemorrhage filling all perimesencephalic cisterns. However, digital subtraction angiography could not locate the hemorrhage source. Her consciousness deteriorated within 7 hours of onset, and a computed tomography scan revealed acute hydrocephalus. We subjected the patient to external ventricular drainage for 10 days. She was discharged after 38 days of hospitalization, when she was physically and neuropsychologically healthy. Repeated digital subtraction angiography performed at the 6-month follow-up did not show any obvious source of hemorrhage except for a variant drainage pattern of the basal vein of Rosenthal. Based on the observations, we diagnosed the patient with PNSAH of a venous origin. CONCLUSIONS: We propose that acute hydrocephalus be suspected in pediatric patients with nonaneurysmal subarachnoid hemorrhage filling all perimesencephalic cisterns, as in adults. We also propose that one of the possible causes of pediatric PNSAH as of venous origin and related to the abnormal drainage pattern of basal vein of Rosenthal and elevation of venous pressure with exercise. Immediate surgical drainage could obtain a good outcome in a symptomatic case.


Asunto(s)
Derivaciones del Líquido Cefalorraquídeo/métodos , Hidrocefalia/etiología , Hidrocefalia/cirugía , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/cirugía , Venas Cerebrales/anomalías , Niño , Drenaje , Femenino , Humanos
6.
Neurol Med Chir (Tokyo) ; 58(10): 442-452, 2018 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-30249918

RESUMEN

Epilepsy surgery aims to control epilepsy by resecting the epileptogenic region while preserving function. In some patients with epileptogenic foci in and around functionally eloquent areas, awake surgery is implemented. We analyzed the surgical outcomes of such patients and discuss the clinical application of awake surgery for epilepsy. We examined five consecutive patients, in whom we performed lesionectomy for epilepsy with awake craniotomy, with postoperative follow-up > 2 years. All patients showed clear lesions on magnetic resonance imaging (MRI) in the right frontal (n = 1), left temporal (n = 1), and left parietal lobe (n = 3). Intraoperatively, under awake conditions, sensorimotor mapping was performed; primary motor and/or sensory areas were successfully identified in four cases, but not in one case of temporal craniotomy. Language mapping was performed in four cases, and language areas were identified in three cases. In one case with a left parietal arteriovenous malformation (AVM) scar, language centers were not identified, probably because of a functional shift. Electrocorticograms (ECoGs) were recorded in all cases, before and after resection. ECoG information changed surgical strategy during surgery in two of five cases. Postoperatively, no patient demonstrated neurological deterioration. Seizure disappeared in four of five cases (Engel class 1), but recurred after 2 years in the remaining patient due to tumor recurrence. Thus, for patients with epileptogenic foci in and around functionally eloquent areas, awake surgery allows maximal resection of the foci; intraoperative ECoG evaluation and functional mapping allow functional preservation. This leads to improved seizure control and functional outcomes.


Asunto(s)
Epilepsia/cirugía , Vigilia , Adulto , Mapeo Encefálico , Estudios de Cohortes , Electrocorticografía , Epilepsia/etiología , Epilepsia/fisiopatología , Femenino , Humanos , Masculino , Resultado del Tratamiento , Adulto Joven
7.
No Shinkei Geka ; 45(12): 1051-1057, 2017 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-29262385

RESUMEN

BACKGROUND: Vagus nerve stimulation(VNS)for patients with intractable epilepsy was approved by the Japan Ministry of Health, Labour and Welfare in 2010. More than 1,500 VNS systems were implanted by the end of August 2016. The aim of the present report is to describe complications we experienced at our department and consider the way to avoid them. METHODS AND PATIENTS: We retrospectively reviewed 139 consecutive patients(122 new implantations and 17 reimplantations)between December 2010 and March 2016. RESULTS: Seven patients demonstrated eight complications. Four patients experienced recurrent nerve paralysis with hoarseness and/or cough that did not require device removal. One patient experienced subsequent aspiration pneumonia. The device was removed in one case due to lead fracture and in three owing to surgical site infection(SSI). CONCLUSION: All recurrent nerve paralysis occurred just after we started VNS implantations. It was presumed that the nerve paralysis was caused by retraction around the vagus nerve. Smaller skin incision and decreased retraction of the surgical field has eliminated this complication. The incidence of infections is reported as 2.2%. Allergic reaction to the VNS device might be one of the causes for SSI in our series. Fracture of the lead was caused by revolving of the pulse generator under the skin. Tight sutures around the pocket or subpectoral placement of a pulse generator is necessary to prevent rotation of the generator depending upon the activity of each patient. This paper provides insight into complications and successful strategies for better outcomes in VNS therapy.


Asunto(s)
Epilepsia Refractaria/etiología , Estimulación del Nervio Vago/efectos adversos , Adolescente , Adulto , Anciano , Niño , Preescolar , Epilepsia Refractaria/prevención & control , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto Joven
8.
Brain Dev ; 39(10): 882-885, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28673533

RESUMEN

Doose syndrome (epilepsy with myoclonic-atonic seizures) is an epilepsy syndrome with an incidence of approximately 1-2% of childhood-onset epilepsies. Although this syndrome is associated with multiple types of generalized seizures, the diagnosis is based on the presence of myoclonic-atonic seizures. Eighteen percent of patients have refractory seizures and intellectual disabilities. There have, however, been a few reports on the efficacy of surgical treatment for Doose syndrome. We describe a case of Doose syndrome in a 10-year-old boy. He developed generalized tonic-clonic seizures at 3years 8months of age and subsequently developed myoclonic-atonic, myoclonic, and tonic seizures. The frequent myoclonic seizures were refractory to multiple antiepileptic medications. His cognitive development was moderately delayed. Anterior four fifths corpus callosotomy was performed at 8years 5months of age. His seizures, especially myoclonic seizures, were markedly reduced. He was given vagus nerve stimulation therapy at 9years and 1month of age, which led to complete resolution of the myoclonic seizures. Corpus callosotomy can be a good treatment strategy in patients with Doose syndrome with medically refractory generalized seizures.


Asunto(s)
Cuerpo Calloso/cirugía , Epilepsias Mioclónicas/cirugía , Epilepsias Mioclónicas/terapia , Niño , Electroencefalografía/métodos , Epilepsia/cirugía , Epilepsia Generalizada/cirugía , Humanos , Masculino , Convulsiones/terapia , Estimulación del Nervio Vago/métodos
9.
J Neurosurg ; 127(4): 790-797, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28059650

RESUMEN

OBJECTIVE Maximum extent of resection (EOR) for lower-grade and high-grade gliomas can increase survival rates of patients. However, these infiltrative gliomas are often observed near or within eloquent regions of the brain. Awake surgery is of known benefit for the treatment of gliomas associated with eloquent regions in that brain function can be preserved. On the other hand, intraoperative MRI (iMRI) has been successfully used to maximize the resection of tumors, which can detect small amounts of residual tumors. Therefore, the authors assessed the value of combining awake craniotomy and iMRI for the resection of brain tumors in eloquent areas of the brain. METHODS The authors retrospectively reviewed the records of 33 consecutive patients with glial tumors in the eloquent brain areas who underwent awake surgery using iMRI. Volumetric analysis of MRI studies was performed. The pre-, intra-, and postoperative tumor volumes were measured in all cases using MRI studies obtained before, during, and after tumor resection. RESULTS Intraoperative MRI was performed to check for the presence of residual tumor during awake surgery in a total of 25 patients. Initial iMRI confirmed no further tumor resection in 9 patients (36%) because all observable tumors had already been removed. In contrast, intraoperative confirmation of residual tumor during awake surgery led to further tumor resection in 16 cases (64%) and eventually an EOR of more than 90% in 8 of 16 cases (50%). Furthermore, EOR benefiting from iMRI by more than 15% was found in 7 of 16 cases (43.8%). Interestingly, the increase in EOR as a result of iMRI for tumors associated mainly with the insular lobe was significantly greater, at 15.1%, than it was for the other tumors, which was 8.0% (p = 0.001). CONCLUSIONS This study revealed that combining awake surgery with iMRI was associated with a favorable surgical outcome for intrinsic brain tumors associated with eloquent areas. In particular, these benefits were noted for patients with tumors with complex anatomy, such as those associated with the insular lobe.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Corteza Cerebral/diagnóstico por imagen , Craneotomía/métodos , Glioma/diagnóstico por imagen , Glioma/cirugía , Imagen por Resonancia Magnética , Monitoreo Intraoperatorio/métodos , Procedimientos Neuroquirúrgicos/métodos , Complicaciones Posoperatorias/prevención & control , Vigilia , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neoplasia Residual , Estudios Retrospectivos
10.
Acta Neurochir (Wien) ; 159(1): 177-184, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27888341

RESUMEN

BACKGROUND: Surgeries for lesions in the dominant hippocampal and parahippocampal gyrus involving the posteromedial temporal regions are challenging to perform because they are located close to Wernicke's area; white matter fibers related with language; the optic radiations; and critical neurovascular structures. We performed a transtemporal approach with awake functional mapping for lesions affecting the dominant posteromedial temporal regions. The aim of this study was to assess the feasibility, safety, and efficacy of awake craniotomy for these lesions. METHODS: We retrospectively reviewed four consecutive patients with tumors or cavernous angiomas located in the left hippocampal and parahippocampal gyrus, which further extended to the posteromedial temporal regions, who underwent awake surgery between December 2014 and January 2016. RESULTS: Four patients with lesions associated with the left hippocampal and parahippocampal gyrus, including the posteromedial temporal area, who underwent awake surgery were registered in the study. In all four patients, cortical and subcortical eloquent areas were identified via direct electrical stimulation. This allowed determination of the optimal surgical route to the angioma or tumor, even in the language-dominant hippocampal and parahippocampal gyrus. In particular, this approach enabled access to the upper part of posteromedial temporal lesions, while protecting the subcortical language-related fibers, such as the superior longitudinal fasciculus. CONCLUSIONS: This study revealed that awake brain mapping can enable the safe resection of dominant posteromedial temporal lesions, while protecting cortical and subcortical eloquent areas. Furthermore, our experience with four patients demonstrates the feasibility, safety, and efficacy of awake surgery for these lesions.


Asunto(s)
Mapeo Encefálico/métodos , Neoplasias Encefálicas/cirugía , Estimulación Eléctrica/métodos , Lateralidad Funcional/fisiología , Procedimientos Neuroquirúrgicos/métodos , Giro Parahipocampal/cirugía , Lóbulo Temporal/cirugía , Vigilia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
11.
J Neurosurg ; 124(3): 791-8, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26295917

RESUMEN

Few studies have examined the clinical characteristics of patients with lesions in the deep parietal operculum facing the sylvian fissure, the region recognized as the secondary somatosensory area (SII). Moreover, surgical approaches in this region are challenging. In this paper the authors report on a patient presenting with SII epilepsy with a tumor in the left deep parietal operculum. The patient was a 24-year-old man who suffered daily partial seizures with extremely uncomfortable dysesthesia and/or occasional pain on his right side. MRI revealed a tumor in the medial aspect of the anterior transverse parietal gyrus, surrounding the posterior insular point. Long-term video electroencephalography monitoring with scalp electrodes failed to show relevant changes to seizures. Resection with cortical and subcortical mapping under awake conditions was performed. A negative response to stimulation was observed at the subcentral gyrus during language and somatosensory tasks; thus, the transcortical approach (specifically, a transsubcentral gyral approach) was used through this region. Subcortical stimulation at the medial aspect of the anterior parietal gyrus and the posterior insula around the posterior insular point elicited strong dysesthesia and pain in his right side, similar to manifestation of his seizure. The tumor was completely removed and pathologically diagnosed as pleomorphic xanthoastrocytoma. His epilepsy disappeared without neurological deterioration postoperatively. In this case study, 3 points are clinically significant. First, the clinical manifestation of this case was quite rare, although still representative of SII epilepsy. Second, the location of the lesion made surgical removal challenging, and the transsubcentral gyral approach was useful when intraoperative mapping was performed during awake surgery. Third, intraoperative mapping demonstrated that the patient experienced pain with electrical stimulation around the posterior insular point. Thus, this report demonstrated the safe and effective use of the transsubcentral gyral approach during awake surgery to resect deep parietal opercular lesions, clarified electrophysiological characteristics in the SII area, and achieved successful tumor resection with good control of epilepsy.


Asunto(s)
Astrocitoma/cirugía , Neoplasias Encefálicas/cirugía , Epilepsia/cirugía , Corteza Somatosensorial , Astrocitoma/complicaciones , Astrocitoma/diagnóstico , Mapeo Encefálico , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Epilepsia/diagnóstico , Epilepsia/etiología , Humanos , Masculino , Adulto Joven
12.
Cancer Invest ; 34(1): 12-5, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26695622

RESUMEN

The authors recently found that 80% of lower-grade gliomas (LGGs) harbored a mutation in IDH1. Intraoperative detection of the mutated IDH1 helps not only differentiate LGGs from other type of brain tumors, but determine the resection border. In the current study, the authors have applied an automated genetic typing involving a quenching probe to detect the mutated IDH1. If tumor cells with the mutated IDH1 contained 10% or more in the mixture of normal and tumor cells, the device could detect it sensitively. The intraoperative assessment of IDH1 mutation is useful in brain tumor surgeries.


Asunto(s)
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Glioma/genética , Glioma/patología , Isocitrato Deshidrogenasa/genética , Mutación , Análisis Mutacional de ADN/métodos , Glioma/diagnóstico , Humanos , Tipificación Molecular/métodos , Tasa de Mutación , Clasificación del Tumor , Polimorfismo de Nucleótido Simple
13.
Biol Trace Elem Res ; 119(1): 10-8, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17914214

RESUMEN

Cadmium (Cd), lead (Pb), and selenium (Se) concentrations in cord whole blood, sampled from 24 women at the time of delivery in a hospital in Tokyo in 2005, were determined by inductively coupled plasma mass spectrometry with a reaction cell. Signal enhancement caused by nonspectroscopic interference for Se was evident and the standard addition technique was essential for correcting the interference. Median concentration in cord bloods was 0.20 ng/g, 6.7 ng/g (0.67 microg/dL), and 191 ng/g for Cd, Pb and Se, respectively. Lead concentration was lower, whereas Se concentration was higher, than those reported in other countries. The trace element concentration was related to the levels of thyroid stimulating hormone (TSH) and free thyroxin (fT4) in the neonatal blood sampled at 4-6 days postpartum. A significantly negative correlation was observed between Cd concentrations in cord blood and TSH concentration in neonatal blood. The result indicated the possible effect of in utero Cd exposure on thyroid hormone status of newborns and that Cd exposure level should be assessed as a covariate in the survey on the relationship between in utero chemicals (e.g., PCBs) exposure and thyroid hormone status.


Asunto(s)
Cadmio/sangre , Sangre Fetal/química , Recién Nacido/sangre , Plomo/sangre , Espectrometría de Masas/métodos , Selenio/sangre , Tirotropina/sangre , Tiroxina/sangre , Humanos , Japón , Valores de Referencia
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...