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1.
BMC Ophthalmol ; 23(1): 479, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993825

RESUMO

BACKGROUND: Conjunctival chemosis (CC) is an extremely rare symptom of pituitary neuroendocrine tumor (PitNET). We report an extremely rare case of PitNET manifesting as severe CC. CASE PRESENTATION: A 48-year-old male was admitted to our hospital with severe CC, proptosis, and ptosis of the right eye. Magnetic resonance imaging demonstrated the tumor mass invading the cavernous sinus (CS) with cystic lesion. The patient underwent emergent endoscopic transsphenoidal surgery, and the pathological diagnosis was PitNET. CC of the right eye remarkably improved after the surgery. Glucocorticoid therapy was performed for right oculomotor nerve palsy, which rapidly improved. The postoperative course was uneventful and the patient was discharged from our hospital without hormone replacement. CONCLUSIONS: CC caused by CS invasion of PitNET can be cured by early surgical treatment. Therefore, PitNET is important to consider in the differential diagnosis of CC.


Assuntos
Seio Cavernoso , Exoftalmia , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Masculino , Humanos , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Seio Cavernoso/patologia , Seio Cavernoso/cirurgia , Túnica Conjuntiva/patologia , Exoftalmia/patologia
2.
No Shinkei Geka ; 51(3): 451-459, 2023 May.
Artigo em Japonês | MEDLINE | ID: mdl-37211734

RESUMO

Because of technological advancements in preserving neurological function during surgery, intraoperative neurophysiological monitoring has become mandatory and increasingly common. Few studies have reported on the safety, feasibility, and reliability of intraoperative neurophysiological monitoring in children, especially infants. The maturation of nerve pathways is not fully achieved until 2 years of age. Moreover, it is often difficult to maintain stable anesthetic depth and hemodynamic status when operating on children. The interpretation of neurophysiological recordings in children is different from that in adults and requires further consideration.


Assuntos
Monitorização Neurofisiológica Intraoperatória , Lactente , Adulto , Humanos , Criança , Reprodutibilidade dos Testes , Procedimentos Neurocirúrgicos
3.
Neuropathology ; 42(4): 323-328, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35723635

RESUMO

Paragonimiasis is a parasitic disease caused by Paragonimus westermani infection, and migration to the brain results in cerebral paragonimiasis. Cerebral paragonimiasis is now extremely rare, but a few cases are still reported. A 48-year-old Japanese woman presented with right-hand convulsion, right-hand numbness, sputum, and fatigue. Chest computed tomography demonstrated multiple nodular lesions, and head computed tomography revealed a hemorrhagic lesion in the left motor cortex. Magnetic resonance imaging revealed multiple small ring-shaped lesions with surrounding edema. Laboratory evaluation demonstrated peripheral eosinophilia. We considered eosinophilic granulomatosis with polyangiitis and started steroid treatment as a diagnostic therapy since we wanted to avoid cerebral lesion biopsy if possible. However, the patient underwent craniotomy surgery after steroid treatment for four months because a new intracerebral mass lesion had appeared. Trematode eggs were detected in the sample, and the final diagnosis was cerebral paragonimiasis. The patient was successfully treated with praziquantel. Cerebral paragonimiasis is extremely rare but should be considered in the differential diagnosis if atypical intracranial hemorrhage and peripheral eosinophilia are observed.


Assuntos
Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Paragonimíase , Erros de Diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Paragonimíase/diagnóstico , Paragonimíase/parasitologia , Paragonimíase/patologia , Esteroides
4.
Adv Tech Stand Neurosurg ; 44: 79-96, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35107674

RESUMO

Extracranial-intracranial (EC-IC) bypass is one of the most fundamental techniques for ischemic cerebrovascular disease (CVD). We describe the standard surgical strategies, advanced techniques, and controversies concerning revascularization of ischemic stroke. The standard surgical strategies and techniques emphasize how to determine surgical indication, which should be decided for symptomatic internal carotid artery or middle cerebral artery (MCA) occlusive disease with misery perfusion detected by quantitative single photon emission computed tomography. Advanced techniques are available for complex situations such as posterior circulation revascularization, Bonnet bypass for common carotid artery obstruction, and various EC-IC bypasses for ischemia in the MCA and/or anterior cerebral artery territories using inter-grafts such as femoral veins and radial arteries, illustrated by our surgical results and experiences. Controversies include endovascular treatment complementary to EC-IC bypass. Finally, we advocate emergent EC-IC bypass for progressive ischemic CVD, particularly for contraindication or unsuccessful treatment after intravenous tissue plasminogen activator administration and/or endovascular thrombolysis. EC-IC bypass surgery can be reliable for ischemic CVD under strict optimal surgical indications using safe and reliable surgical techniques.


Assuntos
Isquemia Encefálica , Revascularização Cerebral , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/cirurgia , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Ativador de Plasminogênio Tecidual/uso terapêutico
5.
Psychiatry Clin Neurosci ; 76(8): 367-376, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35543406

RESUMO

AIM: To establish treatment response biomarkers that reflect the pathophysiology of depression, it is important to use an integrated set of features. This study aimed to determine the relationship between regional brain activity at rest and blood metabolites related to treatment response to escitalopram to identify the characteristics of depression that respond to treatment. METHODS: Blood metabolite levels and resting-state brain activity were measured in patients with moderate to severe depression (n = 65) before and after 6-8 weeks of treatment with escitalopram, and these were compared between Responders and Nonresponders to treatment. We then examined the relationship between blood metabolites and brain activity related to treatment responsiveness in patients and healthy controls (n = 36). RESULTS: Thirty-two patients (49.2%) showed a clinical response (>50% reduction in the Hamilton Rating Scale for Depression score) and were classified as Responders, and the remaining 33 patients were classified as Nonresponders. The pretreatment fractional amplitude of low-frequency fluctuation (fALFF) value of the left dorsolateral prefrontal cortex (DLPFC) and plasma kynurenine levels were lower in Responders, and the rate of increase of both after treatment was correlated with an improvement in symptoms. Moreover, the fALFF value of the left DLPFC was significantly correlated with plasma kynurenine levels in pretreatment patients with depression and healthy controls. CONCLUSION: Decreased resting-state regional activity of the left DLPFC and decreased plasma kynurenine levels may predict treatment response to escitalopram, suggesting that it may be involved in the pathophysiology of major depressive disorder in response to escitalopram treatment.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Maior/terapia , Escitalopram , Humanos , Cinurenina , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Estimulação Magnética Transcraniana
6.
BMC Oral Health ; 22(1): 297, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854344

RESUMO

BACKGROUND: Different perspectives are needed to understand the pathophysiology of burning mouth syndrome (BMS), including physiological and psychological standpoints. The significance of interoception in chronic pain has been suggested. However, few studies have investigated this relationship in BMS. Therefore, we examined the role of interoception in BMS. METHODS: This is a cross-sectional study. BMS patients (N = 64) participated in the study. We used interoceptive accuracy (IAc) based on the heartbeat counting task. Then, participants were divided into high and low IAc groups, and their scores on clinical assessment including pain and psychological evaluation were compared. RESULTS: The Visual Analogue Scale scores indicating pain in low IAc patients, but not high IAc patients, were positively correlated with the Beck Depression Inventory-Second Edition (BDI-II) and the State-Trait Anxiety Inventory-State (STAI-S) Scores. CONCLUSIONS: Interoception might play a role in the pathophysiology of BMS.


Assuntos
Síndrome da Ardência Bucal , Estudos Transversais , Depressão , Humanos , Dor/psicologia , Escalas de Graduação Psiquiátrica
7.
Neuroimage ; 245: 118733, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34800664

RESUMO

Neurofeedback (NF) aptitude, which refers to an individual's ability to change brain activity through NF training, has been reported to vary significantly from person to person. The prediction of individual NF aptitudes is critical in clinical applications to screen patients suitable for NF treatment. In the present study, we extracted the resting-state functional brain connectivity (FC) markers of NF aptitude, independent of NF-targeting brain regions. We combined the data from fMRI-NF studies targeting four different brain regions at two independent sites (obtained from 59 healthy adults and six patients with major depressive disorder) to collect resting-state fMRI data associated with aptitude scores in subsequent fMRI-NF training. We then trained the multiple regression models to predict the individual NF aptitude scores from the resting-state fMRI data using a discovery dataset from one site and identified six resting-state FCs that predicted NF aptitude. Subsequently, the reproducibility of the prediction model was validated using independent test data from another site. The identified FC model revealed that the posterior cingulate cortex was the functional hub among the brain regions and formed predictive resting-state FCs, suggesting that NF aptitude may be involved in the attentional mode-orientation modulation system's characteristics in task-free resting-state brain activity.


Assuntos
Transtorno Depressivo Maior/terapia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Imageamento por Ressonância Magnética , Neurorretroalimentação , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiologia , Adulto , Conectoma , Conjuntos de Dados como Assunto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Descanso
8.
Cancer Sci ; 112(11): 4736-4747, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34536314

RESUMO

Glioblastomas (GBM) often acquire resistance against temozolomide (TMZ) after continuous treatment and recur as TMZ-resistant GBM (TMZ-R-GBM). Lomustine (CCNU) and nimustine (ACNU), which were previously used as standard therapeutic agents against GBM before TMZ, have occasionally been used for the salvage therapy of TMZ-R-GBM; however, their efficacy has not yet been thoroughly examined. Therefore, we investigated the antitumor effects of CCNU and ACNU against TMZ-R-GBM. As a model of TMZ-R-GBM, TMZ resistant clones of human GBM cell lines (U87, U251MG, and U343MG) were established (TMZ-R-cells) by the culture of each GBM cells under continuous TMZ treatment, and the antitumor effects of TMZ, CCNU, or ACNU against these cells were analyzed in vitro and in vivo. As a result, although growth arrest and apoptosis were triggered in all TMZ-R-cells after the administration of each drug, the antitumor effects of TMZ against TMZ-R-cells were significantly reduced compared to those of parental cells, whereas CCNU and ACNU demonstrated efficient antitumor effects on TMZ-R-cells as well as parental cells. It was also demonstrated that TMZ resistance of TMZ-R-cells was regulated at the initiation of DNA damage response. Furthermore, survival in mice was significantly prolonged by systemic treatment with CCNU or ACNU but not TMZ after implantation of TMZ-R-cells. These findings suggest that CCNU or ACNU may serve as a therapeutic agent in salvage treatment against TMZ-R-GBM.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/tratamento farmacológico , Lomustina/uso terapêutico , Nimustina/uso terapêutico , Temozolomida/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/metabolismo , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Glioblastoma/metabolismo , Histonas/metabolismo , Humanos , Injeções Intraperitoneais , Lomustina/administração & dosagem , Metilação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Recidiva Local de Neoplasia/tratamento farmacológico , Nimustina/administração & dosagem , Terapia de Salvação/métodos , Proteínas Supressoras de Tumor/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
9.
BMC Neurol ; 21(1): 119, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731025

RESUMO

BACKGROUND: Intracranial venous hypertension has been associated with a few cases of meningioma secondary to compression of the venous sinus. This is the rare case of small meningioma involving the sigmoid sinus leading to intracranial venous hypertension mimicking venous thrombosis. CASE PRESENTATION: A 39-year-old woman suffered visual dysfunction due to bilateral papilledema. Noncontrast head computed tomography (CT) showed no intracranial space-occupying lesions or hydrocephalus. Cerebrospinal fluid examination revealed high opening pressure. Various image inspections such as three-dimensional CT angiography, magnetic resonance imaging, and cerebral angiography demonstrated a small 2.5-cm lesion causing subtotal occlusion of the dominant right sigmoid sinus. No improvement of clinical manifestations was observed after medical treatment for 6 months, so right presigmoid craniectomy was performed. Operative findings revealed that the tumor was located predominantly involving the sigmoid sinus. The pathological diagnosis was fibrous meningioma. Postoperative fundoscopic examination showed improvement of bilateral papilledema. CONCLUSIONS: We treated a patient presenting with intracranial hypertension due to a small meningioma involving the sigmoid sinus. This unusual case suggests that early surgical strategies should be undertaken to relieve the sinus obstruction.


Assuntos
Cavidades Cranianas/patologia , Hipertensão Intracraniana/etiologia , Neoplasias Meníngeas/complicações , Meningioma/complicações , Adulto , Angiografia Cerebral , Craniotomia/efeitos adversos , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/patologia , Meningioma/cirurgia , Papiledema/etiologia , Trombose dos Seios Intracranianos/diagnóstico , Tomografia Computadorizada por Raios X
10.
BMC Neurol ; 21(1): 25, 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33451289

RESUMO

BACKGROUND: Meningiomas are the most common benign intracranial tumors, and commonly comprise high-vascularizing but slow-growing tumors. On the other hand, meningiomas arising from the ventricular system are of rare occurrence, and spontaneous hemorrhage is an infrequent event. CASE PRESENTATION: We describe here the rare clinical manifestations of a 28-year-old female with acute intracranial hemorrhage located in the trigone of the lateral ventricle who was initially thought to have suffered an acute cerebrovascular accident, but was subsequently confirmed to have a benign intraventricular meningioma. To clarify the clinical features of such a rare course of meningioma, we also present a short literature review of acute intracranial hemorrhage caused by intraventricular meningioma. CONCLUSIONS: Ventricular meningioma presenting with hemorrhage such as acute stroke is a rare event, but recognition of such a pathogenesis is important. Although further accumulation of clinical data is needed, we suggest that early surgery should be undertaken in patients with lateral ventricular meningioma, even if it is not so large or asymptomatic.


Assuntos
Neoplasias do Ventrículo Cerebral/complicações , Hemorragias Intracranianas/etiologia , Neoplasias Meníngeas/complicações , Meningioma/complicações , Adulto , Neoplasias do Ventrículo Cerebral/patologia , Feminino , Humanos , Ventrículos Laterais/patologia , Neoplasias Meníngeas/patologia , Meningioma/patologia
11.
Brain Cogn ; 154: 105806, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34656037

RESUMO

Attention function is thought to be important in chronic pain, with the pathology of chronic pain closely associated with cognitive-emotional components. However, there have been few neuroimaging studies of the relationship between attention function and chronic pain. We used the method of functional connectivity analysis for resting-state fMRI (rs-fMRI) data and the Attention Network Test-Revision (ANT-R) to clarify the attention-related pathology of chronic pain. We performed rs-fMRI and ANT-R on a group of 26 chronic pain (somatoform pain disorder) patients and 28 age-matched healthy controls. A significant group difference in validity effects, a component of ANT-R, emerged (F1,46 = 5.91, p = 0.019), and the chronic pain group exhibited slower reaction times. Decreased brain connectivity of the left insula and left frontal regions was confirmed in chronic pain patients (pFWE < 0.05), and connectivity was negatively correlated with validity effects (r = -0.29, permutation test p = 0.033). Further, decreased functional connectivity strength of the right insula and left temporal gyrus in the chronic pain group were confirmed (pFWE < 0.05). We conclude that poor control of attention function results from deficits of functional connectivity in the left insula and left frontal regions in chronic pain.


Assuntos
Dor Crônica , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Dor Crônica/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Neuroimagem
12.
Psychiatry Clin Neurosci ; 75(2): 46-56, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33090632

RESUMO

AIM: Several studies have reported altered age-associated changes in white matter integrity in bipolar disorder (BD). However, little is known as to whether these age-related changes are illness-specific. We assessed disease-specific effects by controlling for age and investigated age-associated changes and Group × Age interactions in white matter integrity among major depressive disorder (MDD) patients, BD patients, and healthy controls. METHODS: Healthy controls (n = 96; age range, 20-77 years), MDD patients (n = 101; age range, 25-78 years), and BD patients (n = 58; age range, 22-76 years) participated in this study. Fractional anisotropy (FA) derived from diffusion tensor imaging in 54 white matter tracts were compared after controlling for the linear and quadratic effect of age using a generalized linear model. Age-related effects and Age × Group interactions were also assessed in the model. RESULTS: The main effect of group was significant in the left column and body of the fornix after controlling for both linear and quadratic effects of age, and in the left body of the corpus callosum after controlling for the quadratic effect of age. BD patients exhibited significantly lower FA relative to other groups. There was no Age × Group interaction in the tracts. CONCLUSION: Significant FA reductions were found in BD patients after controlling for age, indicating that abnormal white matter integrity in BD may occur at a younger age rather than developing progressively with age.


Assuntos
Transtorno Bipolar/patologia , Transtorno Depressivo Maior/patologia , Substância Branca/patologia , Adulto , Fatores Etários , Idoso , Transtorno Bipolar/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Adulto Jovem
13.
J Stroke Cerebrovasc Dis ; 30(11): 106078, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34500198

RESUMO

OBJECTIVES: The anterior choroidal artery (AchA) is one of the collateral vessels in moyamoya disease (MMD). The incidence of cerebral ischemia in MMD was analyzed through the association between development of the AchA and advancement of MMD stage. MATERIALS AND METHODS: Twelve patients of MMD with cerebral ischemia (infarction; 9 patients, transient ischemic attack; 3 patients) were enrolled. Advancement of MMD was evaluated using Suzuki's stage. The grades in Suzuki's stage were subclassified into a non-progressive stage for grades 1 and 2, and a progressive stage for grades 4 and 5. Dilatation of the AchA was judged as the presence of development of this artery. Development of the AchA was grouped into proximal type and proximal and distal type. RESULTS: Most frequent locations of infarcts were the anterior and parietal lobes in 6 patients each. Development of the AchA was confirmed on the ischemic side in all patients and on the non-ischemic side in 9 patients. Development of the AchA in the progressive stage was limited in the proximal and distal type on both sides. Development of the AchA in the non-progressive stage was the proximal type on the ischemic side. CONCLUSIONS: The cause of cerebral ischemia was possibly associated with inadequate blood supply of the AchA in the non-progressive stage, and the lower blood flow from the internal carotid artery (ICA) in the progressive stage. Disparity between collateral blood flow from the AchA and the blood flow from the ICA was considered to relate to incidence of cerebral ischemia in MMD.


Assuntos
Isquemia Encefálica , Artéria Carótida Interna , Doença de Moyamoya , Isquemia Encefálica/epidemiologia , Artéria Carótida Interna/fisiopatologia , Humanos , Doença de Moyamoya/complicações
14.
No Shinkei Geka ; 49(5): 964-975, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34615756

RESUMO

Decompressive craniectomy(DC)for intracranial hypertension after traumatic brain injury(TBI)can be divided into two treatment strategies: primary DC and secondary DC. DC has an important intracranial pressure-lowering effect; however, the standard treatment has not been established because the treatment policy with respect to surgical indication, optimal timing, and surgical method are often determined according to the empirical rules of each institution. In addition, the effects of DC on clinical outcomes remain unknown. Recently, the results of a large multicenter randomized controlled trial(RCT)about the effects of secondary DC for severe head trauma have been published. The study showed that secondary DC improved the mortality rate but had no effect on functional prognosis. Another RCT about the effects of primary DC for TBI is ongoing and the results are awaited. We herein describe the indications, surgical methods, and issues of DC for TBI based on the results of these clinical trials with a high level of evidence.


Assuntos
Craniectomia Descompressiva , Hipertensão Intracraniana , Humanos , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/cirurgia
15.
Biochem Biophys Res Commun ; 524(3): 723-729, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32035622

RESUMO

Recent research has revealed that glioblastoma (GBM) avoids the immune system via strong expression of indoleamine 2,3-dioxygenase 1 (IDO1). IDO1, an enzyme involved in tryptophan metabolism, is now proposed as a new target in GBM treatment, since several reports have demonstrated that IDO1 expression is related to GBM malignancy. On the other hand, it is well known that glioma stem cells (GSCs) are strongly related to the malignancy of GBM. However, there is as yet no report evaluating the relationship between GSCs and IDO1. We therefore examined the expression levels of IDO1 in GSCs in order to identify a new therapeutic target for GBM based on the immune systems of GSCs. In the present study, we employed human GBM cell lines (U-138MG, U-251MG) and patient-derived GSC model cell lines (0125-GSC, 0222-GSC). GSC model cell lines Rev-U-138MG and Rev-U-251MG were established by culturing U-138MG and U-251MG in serum-free media, while differentiated GBM model cell lines 0125-DGC and 0222-DGC were established by culturing 0125-GSC and 0222-GSC in serum-containing media. The expression levels of stem cell markers (Nanog, Nestin, Oct4 and Sox2) and IDO1 protein and mRNA were determined. Rev-U-138MG and Rev-U-251MG formed spheres and their expression levels of stem cell markers were increased as compared to U-138MG and U-251MG. On the other hand, 0125-DGC and 0222-DGC suffered breakdown of sphere formation, despite the original 0125-GSC and 0222-GSC forming spheres, and their expression levels of the markers were decreased. IDO1 expressions were strongly recognized in Rev-U-138MG, Rev-U-251MG, 0125-GSC and 0222-GSC as compared to U-138MG, U-251MG, 0125-DGC and 0222-DGC. These findings demonstrate that GSCs exhibit treatment resistance with immunosuppression via high expression levels of IDO1, and could represent a novel target for GBM treatment.


Assuntos
Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/patologia , Glioma/enzimologia , Glioma/patologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Células-Tronco Neoplásicas/enzimologia , Células-Tronco Neoplásicas/patologia , Linhagem Celular Tumoral , Meios de Cultura Livres de Soro , Glioblastoma/patologia , Humanos , Interferon beta/metabolismo
16.
J Neurooncol ; 148(1): 17-27, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32367437

RESUMO

PURPOSE: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonß (IFNß) plus temozolomide (TMZ) with that of TMZ alone. EXPERIMENTAL: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. RESULTS: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNß + Radiotherapy (RT) group were found. CONCLUSION: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNß addition were identified.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Interferon beta/uso terapêutico , Temozolomida/uso terapêutico , Adulto , Idoso , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Telomerase/genética , Resultado do Tratamento , Proteínas Supressoras de Tumor/genética , Adulto Jovem
17.
Adv Exp Med Biol ; 1232: 323-329, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893427

RESUMO

Recent guidelines on cardiopulmonary resuscitation (CPR) have stressed the necessity to improve the quality of CPR. Our previous studies demonstrated the usefulness of monitoring cerebral blood oxygenation (CBO) during CPR by near-infrared spectroscopy (NIRS). The present study evaluates whether the NIRO-CCR1, a new NIRS device, is as useful in the clinical setting as the NIRO-200NX. We monitored CBO in 20 patients with cardiac arrest by NIRS. On the arrival of patients at the emergency department, the attending physician immediately assessed whether the patient was eligible for this study after conventional advanced life support and, if eligible, measured CBO in the frontal lobe by NIRS. We found that in all patients, the cerebral blood flow waveform was in synchrony with the chest compressions. Moreover, the tissue oxygenation index increased following cardiopulmonary bypass (CPB) in patients undergoing CPB, including one patient in whom CBO was monitored using the NIRO-CCR1. In addition, although the NIRO-CCR1 could display the pulse rate (Tempo) in real time, Tempo was not always detected, despite detection of the cerebral blood flow waveform. This suggested that chest compressions may not have been effective, indicating that the NIRO-CCR1 also seems useful to assess the quality of CPR. This study suggests that the NIRO-CCR1 can measure CBO during CPR in patients with cardiac arrest as effectively as the NIRO-200NX; in addition, the new NIRO-CCR1 may be even more useful, especially in prehospital fields (e.g. in an ambulance), since it is easy to carry.


Assuntos
Reanimação Cardiopulmonar , Circulação Cerebrovascular , Parada Cardíaca , Monitorização Fisiológica , Oximetria , Espectroscopia de Luz Próxima ao Infravermelho , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/normas , Oximetria/instrumentação , Oximetria/normas , Projetos Piloto , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Espectroscopia de Luz Próxima ao Infravermelho/normas
18.
J Cell Physiol ; 234(8): 13510-13524, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30613977

RESUMO

Interferon ß (IFN-ß) is considered a signaling molecule with important therapeutic potential in cancer since IFN-ß-induced gene transcription mediates antiproliferation and cell death induction. Whereas, TNF-related apoptosis inducing ligand/Apo2 ligand (TRAIL/Apo2L) has emerged as a promising anticancer agent because it induces apoptosis specifically in cancer cells. In this study, we elucidated that IFN-ß augments TRAIL-induced apoptosis synergistically using five human malignant melanoma cells. All of these cells were induced apoptosis by TRAIL. Whereas, the response against IFN-ß was different in amelanotic cells (A375 and CRL1579) and melanotic cells (G361, SK-MEL-28, and MeWo). The responsibility of amelanotic cells against IFN-ß was higher than those of melanotic cells. The synergism of IFN-ß and TRAIL were correlated with the responsibilities of the cells against IFN-ß. The synergistic interaction was confirmed by a combination index based on the Chou-Talalay method. The upregulation of apoptosis in amelanotic cells was caused by very low doses of IFN-ß (over 0.1 IU/ml). Both of p53-mediated intrinsic pathway and Fas-related extrinsic pathway were activated by IFN-ß alone and combination with TRAIL. Further, TRAIL death receptors (DR4 and DR5) were upregulated by a low-dose IFN-ß (over 0.1 IU/ml) and the expression was more promoted by the combination with TRAIL. It was clarified that the upregulation of DR5 is associated with the declination of viability.


Assuntos
Interferon beta/administração & dosagem , Melanoma/tratamento farmacológico , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Expressão Gênica/efeitos dos fármacos , Humanos , Melanoma/metabolismo , Melanoma/patologia , Melanoma Amelanótico/tratamento farmacológico , Melanoma Amelanótico/metabolismo , Melanoma Amelanótico/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Proteínas Recombinantes/administração & dosagem
19.
Psychiatry Clin Neurosci ; 73(9): 560-565, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31102312

RESUMO

AIM: Cognitive behavioral therapy (CBT) is known to be effective for patients with persistent somatoform pain disorder (PSPD). Improvement of negative emotions in interpersonal stressful situations has been reported to reduce PSPD-related clinical pain. However, these associations in CBT remain unclear. Therefore, we examined the relation between changes in negative emotions and clinical pain symptoms after CBT by using a multiple regression analysis that included pain catastrophizing. METHODS: We analyzed negative emotional intensity scores in stressful situations of 38 patients with PSPD who had completed CBT treatment and all the daily worksheets. Negative emotional intensity scores were recorded in daily worksheets during 12 weekly CBT sessions. Scores for the Pain Catastrophizing Scale (PCS), Visual Analogue Scale (VAS) as clinical pain intensity, Beck Depression Inventory - Second Edition (BDI-II), and State-Trait Anxiety Inventory (STAI) were also obtained at pre- and post-treatment. A multiple regression analysis was conducted using changes in VAS scores after CBT as the dependent variable, and changes in negative emotional intensity, PCS, BDI-II, and STAI scores after CBT, age, and sex as independent variables. RESULTS: Negative emotional intensity scores decreased after CBT. In a multiple regression analysis, the emotional changes resulting from CBT depicted a modest positive relation with changes in VAS scores (ß = 0.37; P < 0.05); however, there was no relation between changes in PCS scores after CBT and changes in VAS scores after CBT (ß = 0.03). CONCLUSION: The results show that negative emotions play an important role in the treatment effects of CBT for PSPD.


Assuntos
Adaptação Psicológica , Catastrofização/terapia , Dor Crônica/terapia , Terapia Cognitivo-Comportamental , Emoções , Transtornos Somatoformes/terapia , Adulto , Idoso , Catastrofização/psicologia , Dor Crônica/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Transtornos Somatoformes/psicologia , Adulto Jovem
20.
J Anesth ; 33(5): 579-586, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31392418

RESUMO

PURPOSE: The decrease in maternal regional cerebral blood volume (rCBV) and oxygenation (rCBO) during spinal anesthesia for cesarean section depends on the severity of hypotension. We examined the relationships between changes in the systemic circulatory parameters, cardiac output (CO) and systemic vascular resistance (SVR), and rCBV and rCBO after induction of spinal anesthesia, evaluated by near-infrared spectroscopy (NIRS) and an arterial pressure-based cardiac output monitoring system (APCOs). METHODS: Seventeen patients undergoing elective cesarean section under spinal anesthesia were monitored every 1 min for mean arterial pressure (MAP), heart rate (HR), end-tidal carbon dioxide (EtCO2) and oxygen saturation (SpO2), and at 20 s intervals for CO, SVR, concentrations of oxy-hemoglobin (Hb), deoxy-Hb, total-Hb, and tissue oxygenation index (TOI), until 15 min after the intrathecal injection of bupivacaine. We investigated changes in the parameters from baseline and evaluated correlations between the changes in total-Hb and TOI and changes in CO and SVR, respectively, at the same timepoints. RESULTS: Oxy-Hb, total-Hb, TOI, and SVR significantly decreased and HR significantly increased with a decrease in MAP (P < 0.01). Deoxy-Hb, CO, SpO2, and EtCO2 levels did not change from baseline. There were statistically significant, although weak, positive correlations between both total-Hb and TOI with SVR (total-Hb; r = 0.18, P < 0.01, TOI; r = 0.38, P < 0.01). CONCLUSION: The decreases in both rCBV and rCBO after induction of spinal anesthesia for cesarean section are probably dependent on the decrease in SVR due to spinal anesthesia.


Assuntos
Raquianestesia/métodos , Bupivacaína/administração & dosagem , Cesárea , Adulto , Pressão Arterial , Dióxido de Carbono/metabolismo , Débito Cardíaco/fisiologia , Volume Sanguíneo Cerebral , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipotensão/epidemiologia , Injeções Espinhais , Gravidez , Estudos Prospectivos , Resistência Vascular/fisiologia
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