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INTRODUCTION: Ultrasonography (US) is used as a real-time dynamic imaging modality during neurosurgery. A novel Doppler US technique, Superb Microvascular Imaging (SMI), can be used to visualize low-velocity flow of small vessels at high resolution with high frame rates. We visualized vessel flow using this US SMI technique and contrast agent during cerebrovascular surgery. METHODS: Forty-three patients with an unruptured cerebral aneurysm (control), ischemic and hemorrhagic moyamoya disease, carotid artery stenosis, hemangioblastoma, severe stenosis of the middle cerebral artery, venous angioma, and intracerebral hemorrhage (ICH) underwent neurosurgery with US SMI monitoring using a contrast agent. The diameter, length, and number of penetrating vessels were analyzed in patients with an unruptured cerebral aneurysm (control), moyamoya disease, and ICH. RESULTS: Diameter and length of cerebral penetrating vessels were significantly increased in patients with moyamoya disease and ICH compared to control patients. The number of penetrating vessels was increased in moyamoya disease patients compared to control and ICH patients. In hemorrhagic moyamoya disease, flow in the penetrating vessels originated from a deep periventricular point and extended to the cerebral surface. Pulsatile cerebral aneurysms during clipping surgery and carotid artery stenosis during carotid endarterectomy were easily identified by SMI. Drastically increased vessel flow in patients with a hemangioblastoma or a venous angioma was observed. CONCLUSION: Using the US SMI technique and contrast agent, we obtained useful flow information of the vascular disease structure and intracerebral deep small vessels during cerebrovascular surgery. Further quantitative analysis will be informative and helpful for cerebrovascular surgery.
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Estenose das Carótidas , Hemangioblastoma , Aneurisma Intracraniano , Doença de Moyamoya , Humanos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Meios de Contraste , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Ultrassonografia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Circulação CerebrovascularRESUMO
BACKGROUND: Patients with severe steno-occlusive disease of a main cerebral artery without causative lesions on magnetic resonance imaging (MRI) often develop cognitive impairment. However, the effects of revascularization surgery and the source of the cognitive impairment remain unclear. Therefore, we investigated the early postoperative course of cognitive function and its association with cerebral blood flow (CBF), cerebrovascular reserve (CVR), white matter disease (WMD), lacunar infarction, and cerebrovascular risk factors. METHODS: Cognitive function was examined using neurobehavioral cognitive status examination (COGNISTAT) in 52 patients with steno-occlusive disease of a main cerebral artery before and at 6 months after superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We examined how cognition changed before and at 1, 3, and 6 months after STA-MCA anastomosis in 27 of 52 patients. CVR and CBF were calculated from 123I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography, in addition to other cerebrovascular risk factors in 34 of 52 patients. Cerebral infarction and WMD (periventricular hyperintensity [PVH] and deep subcortical white matter hyperintensity) were also evaluated preoperatively by MRI. RESULTS: COGNISTAT scores improved at 1 month after STA-MCA anastomosis in patients with severe steno-occlusive disease of a main cerebral artery. Multiple stepwise regression analysis revealed that CVR (regression coefficient = -2.237, p = 0.0020) and PVH (regression coefficient = 2.364, p = 0.0029) were the best predictors of postoperative improvement in COGNISTAT scores (R 2 = 0.415; p = 0.0017). CONCLUSION: Cognitive function improves in relation to preoperative CVR and PVH early after STA-MCA anastomosis in patients with steno-occlusive disease of a main cerebral artery.
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Revascularização Cerebral , Disfunção Cognitiva , Humanos , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/cirurgia , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Imageamento por Ressonância Magnética , Fatores de Risco , Artérias Temporais/cirurgia , Circulação Cerebrovascular/fisiologia , Revascularização Cerebral/métodosRESUMO
A 52-year-old man underwent pneumonectomy of the left lung for previously diagnosed primary spindle cell carcinoma (pT4aN1M0, stage III B) with programmed death-ligand 1 expression (tumor proportion score ≥95%) and without epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase fusion gene. However, brain metastasis and chest wall tumor relapse occurred. Considering insufficient improvement with gamma knife treatment for brain metastasis and combination chemotherapy (paclitaxel, carboplatin, and bevacizumab), pembrolizumab monotherapy and palliative irradiation therapy for chest metastases were started after brain tumor volume reduction using craniotomy. Brain edema and chest wall metastases markedly improved following a pseudoprogression of the brain edema accompanied by a performance status decline; this effect continued until 11 cycles of pembrolizumab administration.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Encefálicas/terapia , Carcinoma/terapia , Neoplasias Pulmonares/terapia , Neoplasias Torácicas/terapia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/secundário , Carcinoma/secundário , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pneumonectomia/métodos , Neoplasias Torácicas/secundárioRESUMO
Objective Esophageal eosinophilia (EE), a histological hallmark of eosinophilic esophagitis, is classified into two endoscopic phenotypes: localized and diffuse EE. Our aim was to determine the prevalence of EE localized in the lower esophagus and to describe its clinical features in comparison with diffuse EE. Methods Data from 81 consecutive patients with EE were retrospectively investigated. EE was histologically defined as ≥15 eosinophils per high-power field. Based on the endoscopic appearance with a histological assessment, EE was classified as either diffuse or localized type. We compared the clinical features, including the medical treatment and natural course, between the two types. Results Of the 81 patients, 52 (64.2%) had diffuse EE, and 29 (35.8%) had localized EE. Among men patients, localized EE was significantly more common than diffuse EE. In localized EE, dysphagia and food impaction were less prevalent, and the presence of rings was significantly less common than in diffuse EE. Acid-suppressive therapy was administered to only 3 of the 29 patients with localized EE. In asymptomatic patients, especially those with localized EE, endoscopic abnormalities did not worsen but rather improved in some findings, such as with regard to furrows or exudate, during the natural course of three years without medical treatment. Conclusion Localized EE has a strong predilection for men patients and accounted for more than one third of all cases of EE. This condition appears to be less symptomatic and necessitates milder medical treatment than diffuse EE and might not worsen progressively.
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Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/fisiopatologia , Esofagite Eosinofílica/diagnóstico por imagem , Esofagite Eosinofílica/fisiopatologia , Esofagoscopia/métodos , Avaliação de Sintomas/métodos , Adolescente , Adulto , Transtornos de Deglutição/epidemiologia , Esofagite Eosinofílica/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Estudos Retrospectivos , Fatores Sexuais , Adulto JovemRESUMO
INTRODUCTION: While remarkable progress has been made in standard treatments for head and neck squamous cell carcinomas (HNSCCs), the long-term survival remains at an unsatisfactory 40-50%. To improve the survival rate, biomarkers for optimal treatment selection and prognostic prediction, as well as novel, low-toxicity treatment strategies, are required. Galanin receptor (GALR) 1 and GALR2 are well-studied tumor suppressors in HNSCCs. Compared with other clinicopathological factors, the epigenetic variants of GALRs have been found to be the most powerful markers to predict the prognosis of HNSCC patients. Areas covered: This review outlines the functions and signaling pathways of GALRs and explains the potential of GALR promoter methylation as a biomarker for HNSCC prognosis. We also summarize recent developments in promoter methylation studies in HNSCC and indicate future directions for GALR promoter methylation studies. Expert commentary: GALR studies have highlighted two major aspects with implications in HNSCC - that G-protein coupled receptors (GPCRs) act as tumor suppressor genes and that GALR promoter methylation is significantly related to the carcinogenesis of HNSCC. The findings of GALR studies can be applied to studies on other GPCRs and further in-depth DNA methylation studies. Deeper insights into GPCR epigenetics are expected to markedly improve HNSCC treatment.
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Biomarcadores Tumorais , Metilação de DNA , DNA de Neoplasias , Neoplasias de Cabeça e Pescoço , Proteínas de Neoplasias , Receptores de Galanina , Carcinoma de Células Escamosas de Cabeça e Pescoço , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Epigênese Genética , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Regiões Promotoras Genéticas , Receptores de Galanina/genética , Receptores de Galanina/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismoRESUMO
A 31-year-old man presented with a sudden-onset headache, right hemiparesis, and dysarthria on day 0 and was diagnosed with acute ischemic stroke due to dissection of the left intracranial internal carotid artery with middle cerebral artery extension. His symptoms progressed despite the institution of treatment, suggesting progression of the dissection. On day 5 after symptom onset, the patient underwent superficial temporal artery-middle cerebral artery anastomosis. No new ischemic stroke event occurred after surgery. Cerebral angiography performed 6 months after surgery showed spontaneous resolution of the dissection. The patient recovered to a modified Rankin Scale score of 2 and was able to return to work. The results of the present case suggest that superficial temporal artery-middle cerebral artery anastomosis is an effective treatment for ischemic stroke due to dissection of the intracranial internal carotid artery with middle cerebral artery extension.
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Salivary duct carcinoma (SDC) constitutes one of the most aggressive cancers in the salivary gland and is associated with a poor prognosis; however, no established systemic therapy options are available. SDC exhibits biological similarity to prostate and breast cancers, therefore anti-hormone therapy and molecular target therapies are available, however with limited beneficial effects. Galanin and galanin receptors (GALRs) are well established as molecular biomarkers to predict the survival rate and risk of recurrence of head and neck squamous cell carcinoma. The present study investigated the clinicopathological features of patients with SDC and the methylation status of their galanin and GALR genes to demonstrate the prognostic value for this disease. The median overall survival (OS) was 37.2 months. T-stage, N-stage, disease stage, tumor size, and preoperative facial paralysis were significantly associated with OS, whereas human epidermal growth factor receptor 2 (HER2) overexpression was not. GALR1 and GALR2 methylation rates in tumor tissues were significantly increased compared with normal tissues with 9.85- and 4.49-fold increase, respectively. p27kip1 and p57kip2 expression significantly inversely correlated with the methylation rate of GALR1 and GALR2. In addition, the observed GALR1 and/or GALR2 methylation rates were significantly correlated with a decrease in OS. These results suggest that GALR1 and GALR2 may serve as potential prognostic factors and therapeutic targets in SDC.
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OBJECTIVES: Symptomatic cerebral infarction (CI) can occur in patients without main cerebral artery stenosis or occlusion. This study investigated the unique features of carotid artery plaque and white matter disease (WMD) in patients with symptomatic CI and transient ischemic attack (TIA) but without stenosis or occlusion of a main cerebral artery. PATIENTS AND METHODS: We studied 647 patients who underwent both carotid ultrasound examination and brain magnetic resonance images. Plaque score (PS), plaque number, maximal plaque intima-media thickness and grades of WMD were examined. Subjects were divided into four groups, the CI group, TIA group, myocardial infarction (MI) group and risk factor (RF) group. Plaque and WMD were analyzed in cerebral ischemia group (CI and TIA), compared to non-cerebral ischemia groups and to a high PS group and a high WMD grade group from the RF group. RESULTS: Both of each value of plaque and grades of WMD in the cerebral ischemia group were significantly higher than those in other groups. Grades of WMD in the cerebral ischemia group were significantly higher than those in the high PS group, although there was no significant difference of the each value of plaque between the two groups. The each value of plaque in the cerebral ischemia group was also significantly higher than those in the high WMD grade group, although there was no significant difference of grade of WMD between the two groups. CONCLUSION: Simultaneous increases in carotid artery plaque and WMD are associated with symptomatic CI, which is not caused by stenosis or occlusion of a main cerebral artery.
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Isquemia Encefálica/patologia , Estenose das Carótidas/patologia , Infarto Cerebral/patologia , Placa Aterosclerótica/patologia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Espessura Intima-Media Carotídea/efeitos adversos , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico , Feminino , Humanos , Ataque Isquêmico Transitório/complicações , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico , Fatores de RiscoRESUMO
When a wide polygonal dural window is created, a short dural incision length is preferred by surgeons because suturing a wastefully long incision line during closure is troublesome. A locator to facilitate making the shortest dural incision when creating a polygonal dural window would be helpful. We geometrically analyzed the shortest incision design for a pentagonal dural window and produced a simple locator for intraoperatively implementing this design. The design for a pentagonal dural window with the shortest incision is the same as the design for a minimum Steiner tree (MST) problem with five vertices. The MST consists of three interconnected Steiner points (SPs) with three equal, radiating branches. We produced a template of the features of the MST for a polygon (MST template) as a locator. The MST template consists of several uniform Steiner units (SUs), each of which has an SP at the center and three wings that branch off of the SP, and each SU also has three slits through which the wings of another unit can pass. This mechanism allows us to freely adjust the distance between the SPs of separate SUs. In clinical practice, we can create the shortest incision design for a quadrilateral or pentagon by arranging MST templates combining two or three SUs. If we open a wide dural window, the total incision lengths created using our method are 1-5 cm shorter than conventional incisions. The MST template accurately and easily reveals the shortest incision design.
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Dura-Máter/cirurgia , Procedimentos Neurocirúrgicos/métodos , Humanos , Conceitos Matemáticos , Técnicas de SuturaRESUMO
BACKGROUND: Intraoperative monitoring of cochlear nerve action potential (CNAP) has been used in patients with small vestibular schwannoma (<15 mm) to preserve cochlear nerve function. We performed surgery for a larger vestibular schwannoma under CNAP monitoring with the aim of preserving cochlear nerve function, and compared the data with findings from 10 patients with hemifacial spasm who underwent microvascular decompression surgery. CASE DESCRIPTION: We report the case of a patient with a 26-mm vestibular schwannoma and normal hearing function who underwent neurosurgery under electrophysiological monitoring of the facial and cochlear nerves. Amplitudes of evoked facial muscle responses were maintained at approximately 70% during the operation. The latency of wave V on brainstem auditory evoked potential (BAEP) increased by 0.5 ms, and amplitude was maintained at approximately 70% of the value at the beginning of the operation. Latencies of P1, N1, and P2 on CNAP did not change intraoperatively. These latencies were comparable to those of 10 normal patients with hemifacial spasm. CNAP monitoring proved very useful in confirming the location of the cochlear nerve in the operative field and preserving cochlear nerve function. Both facial nerve function and hearing acuity were completely preserved after tumor removal, and wave V latency on BAEP returned to normal and was maintained in the normal range for at least 2 years. CONCLUSIONS: CNAP monitoring is extremely useful for preserving the function of the unseen cochlear nerve during vestibular schwannoma surgery.
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Cóclea/cirurgia , Nervo Coclear/cirurgia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Audição/fisiologia , Neuroma Acústico/cirurgia , Humanos , Masculino , Cirurgia de Descompressão Microvascular/métodos , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Neuroma Acústico/diagnóstico , Neuroma Acústico/fisiopatologia , Procedimentos Neurocirúrgicos/métodosRESUMO
OBJECTIVE: In patients with severe steno-occlusive disease of a main cerebral artery, decreased cerebrovascular reserve (CVR) and cognitive impairment without causative focal lesions on magnetic resonance imaging have been reported. We examined ipsilateral and contralateral CVR and cognition before and after superficial temporal artery-middle cerebral artery (MCA) anastomosis operation in patients with internal carotid artery (ICA) or MCA occlusion. METHODS: In 30 patients with ICA or MCA occlusion, cognitive impairment, and decreased CVR, we examined cognition, CVR, leukoaraiosis grades, and blood data. Data from 15 patients who underwent anastomosis were compared to that in 15 patients who did not undergo anastomosis, and to bilateral data already reported on 65 patients with severe steno-occlusive disease. RESULTS: Cerebral blood flow, CVR, and cognition improved after anastomosis compared to before, and compared to patients without anastomosis; improved values were maintained for 5years. CVR recovered after anastomosis, matching the linear relationship between ipsilateral and contralateral CVR seen in the 65 patients. CONCLUSION: The postoperative improvement in cognition and synchronized recovery on the regression line between CVR of the ipsilateral occlusion and contralateral sides may suggest that the CVR is widespread and nonselectively related to cognitive function.
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Estenose das Carótidas/cirurgia , Revascularização Cerebral , Disfunção Cognitiva/cirurgia , Infarto da Artéria Cerebral Média/cirurgia , Artéria Cerebral Média/cirurgia , Artérias Temporais/cirurgia , Idoso , Anastomose Cirúrgica , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/complicações , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/psicologia , Circulação Cerebrovascular , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/psicologia , Modelos Lineares , Masculino , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Testes Neuropsicológicos , Recuperação de Função Fisiológica , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do TratamentoRESUMO
BACKGROUND: When an internal carotid artery (ICA) occludes, a patient may develop cerebral infarction (CI). We investigated whether CI caused by ICA occlusion (ICAO) is associated with collateral flow through the anterior and posterior communicating arteries (ACoA and PCoA). METHODS: In 100 patients with ICAO, we investigated CI and white matter disease by performing an MRI and the anatomy of the ACoA and PCoA were investigated by performing magnetic resonance angiography. All patients were divided into the symptomatic CI group or the no-CI group. The collateral flow pathway was estimated by the anterior cerebral artery (ACA)-PCoA score and the collateral flow volume after ICAO was estimated by the middle cerebral artery (MCA) flow score, based on how well the MCA was visualized. RESULTS: Of 100 patients with ICAO, the symptomatic CI group included 36 patients. ACA-PCoA score and white matter disease grades were significantly higher in the CI group (indicating poor collateral flow). More than 80% of patients with an ACA-PCoA score of 4 (poor collateral) experienced symptomatic CI. Thirty-one symptomatic CI patients (86%) had an MCA flow score of 1 or 2 (decreased MCA flow). CONCLUSION: The ACA-PCoA score and white matter disease grade may suggest an increased risk of CI following ICAO.
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Estenose das Carótidas/complicações , Infarto Cerebral/patologia , Circulação Colateral/fisiologia , Leucoencefalopatias/patologia , Adulto , Idoso , Artéria Carótida Interna/patologia , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Leucoencefalopatias/etiologia , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Neuronavigation based on preoperative magnetic resonance imaging has been developed as a useful tool to improve visibility of the surgical site in the operative field. Ultrasonography (US) monitoring has also been used as a reliable imaging technique, providing real-time information during neurosurgical operations. We combined the latest innovative imaging technique for detecting very low-flow components, Superb Microvascular Imaging (SMI), with US monitoring during brain tumor surgery. CASE DESCRIPTION: Fifteen patients diagnosed with brain tumor (8 malignant and 7 benign) underwent neurosurgery with US monitoring using an Aplio 400/500 US system with the new SMI technique (imaging frequency, 10-12 MHz; frame rate, 28-31 Hz). Features of the SMI images in the gray scale mode include 1) visualization of low-velocity flow with minimal motion artifact, 2) high resolution of images, and 3) high frame rates. The tumors, tumor vessels, compressed and shifted healthy vessels, and cistern were clearly visualized on the SMI images in the gray scale mode, detailing the characteristics of healthy brain tissue (vertically penetrating, fine, straight vessels), glioblastoma (rounding, dilating, and bending vessels), low-grade glioma (fine and straight vessels), meningioma (many large and branching vessels), and lymphoma (less vascular, low echoic tumor) and demonstrating the tumor-defined border. We also performed biopsies under US monitoring with SMI. CONCLUSIONS: We combined SMI technique with US monitoring during brain tumor surgery and observed healthy and tumor vessels. Further research is important for the development of a more precise and reliable neurosurgery.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Microvasos/diagnóstico por imagem , Microvasos/cirurgia , Monitorização Intraoperatória/métodos , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuronavegação/métodos , Procedimentos Neurocirúrgicos/métodosRESUMO
OBJECTIVE: Subarachnoid hemorrhage (SAH) causes cerebral ischemia and drastically worsens the clinical status at onset. However, the arterial flow is surprisingly well maintained on the cerebral surface. We investigated cortical microcirculatory changes in the super acute phase of SAH using two-photon laser scanning microscopy (TPLSM). METHODS: SAH was induced at the skull base in 10 mice using a prone endovascular perforation model. Before SAH, and 1, 2, 5, 10, 20, 30 and 60min after SAH, the cortical microcirculation was observed with TPLSM through a cranial window. Diameters of penetrating and precapillary arterioles were measured and red blood cell (RBC) velocities in precapillary arterioles were analyzed using a line-scan method after administration of Q-dot 655 nanocrystals. RESULTS: One minute after SAH, RBC velocity and flow in precapillary arterioles drastically decreased to <20% of the pre-SAH values, while penetrating and precapillary arterioles dilated significantly. Subsequently, the arterioles either dilated or constricted inconsistently for 60min with continual decreases in RBC velocity and flow in the arterioles, suggesting neurovascular dysfunction. CONCLUSION: SAH caused sudden worsening of the cortical arteriolar velocity and flow at onset. The neurovascular unit cannot function sufficiently to maintain cortical microcirculatory flow in the super acute phase of SAH.
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Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Microcirculação , Hemorragia Subaracnóidea/patologia , Análise de Variância , Animais , Astrócitos/metabolismo , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Imageamento Tridimensional , Masculino , Camundongos , Camundongos Transgênicos , Microscopia Confocal , Hemorragia Subaracnóidea/diagnóstico por imagem , Fatores de TempoRESUMO
BACKGROUND: It is believed that increased intracranial pressure immediately after subarachnoid hemorrhage (SAH) causes extensive brain ischemia and results in worsening clinical status. Arterial flow to the cerebral surfaces is clinically well maintained during clipping surgery regardless of the severity of the World Federation of Neurological Societies grade after SAH. To explore what kinds of changes occur in the cortical microcirculation, not at the cerebral surface, we examined cortical microcirculation after SAH using two-photon laser scanning microscopy (TPLSM). METHODS: SAH was induced in mice with an endovascular perforation model. Following continuous injection of rhodamine 6G, velocities of labeled platelets and leukocytes and unlabeled red blood cells (RBCs) were measured in the cortical capillaries 60 min after SAH with a line-scan method using TPLSM, and the data were compared to a sham group and P-selectin monoclonal antibody-treated group. RESULTS: Velocities of leukocytes, platelets, and RBCs in capillaries decreased significantly 60 min after SAH. Rolling and adherent leukocytes suddenly prevented other blood cells from flowing in the capillaries. Flowing blood cells also decreased significantly in each capillary after SAH. This no-reflow phenomenon induced by plugging leukocytes was often observed in the SAH group but not in the sham group. The decreased velocities of blood cells were reversed by pretreatment with the monoclonal antibody of P-selection, an adhesion molecule expressed on the surfaces of both endothelial cells and platelets. CONCLUSIONS: SAH caused sudden worsening of cortical microcirculation at the onset. Leukocyte plugging in capillaries is one of the reasons why cortical microcirculation is aggravated after SAH.
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Circulação Cerebrovascular , Leucócitos/patologia , Microcirculação , Hemorragia Subaracnóidea/fisiopatologia , Animais , Velocidade do Fluxo Sanguíneo , Masculino , Camundongos , Hemorragia Subaracnóidea/sangueRESUMO
Barrett's esophagus (BE), a premalignant condition to Barrett's adenocarcinoma (BAC), is closely associated with chronic inflammation due to gastro-esophageal reflux. Caudal type homeobox 2 (CDX2), a representative marker of BE, is increased during the metaplastic and neoplastic transformation of BE. Nitric oxide (NO) has been proposed to be a crucial mediator of Barrett's carcinogenesis. We previously demonstrated that CDX2 might be induced directly under stimulation of large amounts of NO generated around the gastro-esophageal junction (GEJ) by activating epithelial growth factor receptor in a ligand-independent manner. Thus, we reviewed recent developments on the role of NO in Barrett's carcinogenesis. Notably, recent studies have reported that microbial communities in the distal esophagus are significantly different among groups with a normal esophagus, reflux esophagitis, BE or BAC, despite there being no difference in the bacterial quantity. Considering that microorganism components can be one of the major sources of large amounts of NO, these studies suggest that the bacterial composition in the distal esophagus might play an important role in regulating NO production during the carcinogenic process. Controlling an inflammatory reaction due to gastro-esophageal reflux or bacterial composition around the GEJ might help prevent the progression of Barrett's carcinogenesis by inhibiting NO production.
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OBJECTIVE: Patients with severe steno-occlusive disease of a main cerebral artery may demonstrate cognitive impairment without identification of causative lesions on magnetic resonance imaging. We investigated whether cognitive impairment in these patients is associated with regional cerebral blood flow (rCBF), leukoaraiosis, risk factors of atherosclerosis and cerebrovascular reserve (CVR), which shows so-called clinical neurovascular function. METHODS: In 65 patients with severe steno-occlusive disease of an internal carotid artery or a middle cerebral artery (MCA) and no cerebral infarction (CI), we examined cognitive function with COGNISTAT, grades of leukoaraiosis, and CBF and CVR as calculated by iodine-123-N-isopropyl-p-iodoamphetamine single photon emission computed tomography and blood data. We compared such values of the left and right sided diseases. rCBF and CVR on the affected side were compared to other side. RESULTS: Logistic regression analysis revealed that CVR correlated with cognitive impairment. There was no significant difference in rCBF, CVR, or COGNISTAT score when comparing the left and right sided diseases. There were good correlations between CBF or CVR of the ipsilateral MCA area and ipsilateral and contralateral other areas. CONCLUSION: Cognitive impairment is associated with CVR in the whole brain. Nonselective widespread neurovascular mild dysfunction can be a reason for cognitive impairment in patients with severe steno-occlusive disease of a main cerebral artery and no CI.
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Arteriopatias Oclusivas/complicações , Doenças Arteriais Cerebrais/complicações , Transtornos Cognitivos/etiologia , Idoso , Arteriopatias Oclusivas/fisiopatologia , Arteriopatias Oclusivas/psicologia , Artéria Carótida Interna/fisiopatologia , Doenças Arteriais Cerebrais/fisiopatologia , Doenças Arteriais Cerebrais/psicologia , Circulação Cerebrovascular/fisiologia , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/fisiopatologia , Testes NeuropsicológicosRESUMO
Therapeutic outcome in head and neck squamous cell carcinoma (HNSCC) is poor in most advanced cases. To improve therapeutic efficiency, novel therapeutic targets and prognostic factors must be discovered. Our studies have identified several G protein-coupled receptors (GPCRs) as promising candidates. Significant epigenetic silencing of GPCR expression occurs in HNSCC compared with normal tissue, and is significantly correlated with clinical behavior. Together with the finding that GPCR activity can suppress tumor cell growth, this indicates that GPCR expression has potential utility as a prognostic factor. In this review, we discuss the roles that galanin receptor type 1 (GALR1) and type 2 (GALR2), tachykinin receptor type 1 (TACR1), and somatostatin receptor type 1 (SST1) play in HNSCC. GALR1 inhibits proliferation of HNSCC cells though ERK1/2-mediated effects on cell cycle control proteins such as p27, p57, and cyclin D1, whereas GALR2 inhibits cell proliferation and induces apoptosis in HNSCC cells. Hypermethylation of GALR1, GALR2, TACR1, and SST1 is associated with significantly reduced disease-free survival and a higher recurrence rate. Although their overall activities varies, each of these GPCRs has value as both a prognostic factor and a therapeutic target. These data indicate that further study of GPCRs is a promising strategy that will enrich pharmacogenomics and prognostic research in HNSCC.
Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Receptores Acoplados a Proteínas G/metabolismo , Galanina/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Somatostatina/metabolismo , Taquicininas/metabolismoRESUMO
Solitary fibrous tumor (SFT) is a distinctive, relatively uncommon soft-tissue neoplasm that usually arises from the pleura. It occurs at various sites; head and neck lesions are very rare. While most of these tumors have a benign course, a small number have malignant potential. We describe a rare case of SFT arising from the left palatine tonsil in a 66-year-old Japanese woman. The mass was completely resected. Immunohistochemical studies were strongly positive for CD34 and bcl-2, mildly positive for phosphorylated protein kinase B and phosphorylated extracellular signal-regulated kinase 1/2, and negative for platelet-derived growth factor receptor alpha and p53. These findings suggested that this tumor was benign. The patient showed no evidence of recurrence during 2 years of follow-up. We believe that the candidate prognostic marker should be checked to distinguish malignant from benign SFTs.
Assuntos
Tonsila Palatina/patologia , Tumores Fibrosos Solitários/patologia , Neoplasias Tonsilares/patologia , Antígenos CD34/análise , Feminino , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tonsila Palatina/cirurgia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Tumores Fibrosos Solitários/cirurgia , Neoplasias Tonsilares/cirurgiaRESUMO
BACKGROUND AND AIM: In Japan, after the revision of the gastrointestinal endoscopic guidelines for patients taking antithrombotics, endoscopic biopsies were permitted while continuing antithrombotic treatment. However, the risk of bleeding after the biopsy with or without cessation of antithrombotics has not been fully evaluated because bleeding events are very rare. The aim of this prospective study was to evaluate the risk for bleeding after upper gastrointestinal biopsy without cessation of antithrombotics. METHODS: Consecutive patients who underwent upper gastrointestinal endoscopic biopsy from December 2011 to March 2014 were enrolled in this study. Antithrombotic medication and its cessation status was checked at enrollment. To confirm bleeding events associated with biopsy, medical examination at the hospital or direct confirmation by telephone was done within 1 month after the biopsy. RESULTS: Among the 3758 patients who underwent endoscopic biopsies, 394 patients (10.5%) were medicated with antithrombotics, and 286 of them (72.6% of the total antithrombotics users) did not undergo cessation. Bleeding after the biopsy occurred in six cases (0.15%, 95% CI; 0.09%â¼0.22%), but there was only one case that had continued taking antithrombotics. The incidence of bleeding after biopsy was not significantly higher in the patients who had continued taking antithrombotics compared with the others (0.35% vs 0.14%, P = 0.38). CONCLUSION: This prospective study showed that continuation of antithrombotics did not increase the bleeding risk after upper gastrointestinal endoscopic biopsy.