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1.
J Pediatr Hematol Oncol ; 46(7): e550-e555, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39008535

RESUMO

Blinatumomab is a CD3/CD19-directed bispecific T-cell engager used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Although blinatumomab has shown efficacy, it can cause serious adverse events, including cytokine release syndrome and neurological events. Among the neurological events, encephalopathy is rare, and knowledge is lacking. Herein, we present a pediatric case of blinatumomab-associated encephalopathy that initially presented with refractory convulsions and later developed into a cerebral infarction. The patient experienced prolonged paralysis and increased brain damage.


Assuntos
Anticorpos Biespecíficos , Encefalopatias , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Encefalopatias/induzido quimicamente , Encefalopatias/patologia , Masculino , Criança , Antineoplásicos/efeitos adversos , Feminino
2.
Sensors (Basel) ; 24(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38931649

RESUMO

Understanding past and current trends is crucial in the fashion industry to forecast future market demands. This study quantifies and reports the characteristics of the trendy walking styles of fashion models during real-world runway performances using three cutting-edge technologies: (a) publicly available video resources, (b) human pose detection technology, and (c) multivariate human-movement analysis techniques. The skeletal coordinates of the whole body during one gait cycle, extracted from publicly available video resources of 69 fashion models, underwent principal component analysis to reduce the dimensionality of the data. Then, hierarchical cluster analysis was used to classify the data. The results revealed that (1) the gaits of the fashion models analyzed in this study could be classified into five clusters, (2) there were significant differences in the median years in which the shows were held between the clusters, and (3) reconstructed stick-figure animations representing the walking styles of each cluster indicate that an exaggerated leg-crossing gait has become less common over recent years. Accordingly, we concluded that the level of leg crossing while walking is one of the major changes in trendy walking styles, from the past to the present, directed by the world's leading brands.


Assuntos
Marcha , Caminhada , Humanos , Caminhada/fisiologia , Análise Multivariada , Marcha/fisiologia , Análise por Conglomerados , Análise de Componente Principal , Fenômenos Biomecânicos/fisiologia , Gravação em Vídeo/métodos , Postura/fisiologia
3.
Sensors (Basel) ; 24(16)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39204793

RESUMO

The accurate estimation of lower-limb joint angles and moments is crucial for assessing the progression of orthopedic diseases, with continuous monitoring during daily walking being essential. An inertial measurement unit (IMU) attached to the lower back has been used for this purpose, but the effect of IMU misalignment in the frontal plane on estimation accuracy remains unclear. This study investigated the impact of virtual IMU misalignment in the frontal plane on estimation errors of lower-limb joint angles and moments during walking. Motion capture data were recorded from 278 healthy adults walking at a comfortable speed. An estimation model was developed using principal component analysis and linear regression, with pelvic accelerations as independent variables and lower-limb joint angles and moments as dependent variables. Virtual IMU misalignments of -20°, -10°, 0°, 10°, and 20° in the frontal plane (five conditions) were simulated. The joint angles and moments were estimated and compared across these conditions. The results indicated that increasing virtual IMU misalignment in the frontal plane led to greater errors in the estimation of pelvis and hip angles, particularly in the frontal plane. For misalignments of ±20°, the errors in pelvis and hip angles were significantly amplified compared to well-aligned conditions. These findings underscore the importance of accounting for IMU misalignment when estimating these variables.


Assuntos
Pelve , Caminhada , Humanos , Caminhada/fisiologia , Masculino , Feminino , Adulto , Pelve/fisiologia , Fenômenos Biomecânicos/fisiologia , Extremidade Inferior/fisiologia , Articulação do Quadril/fisiologia , Aceleração , Adulto Jovem , Amplitude de Movimento Articular/fisiologia , Articulação do Joelho/fisiologia , Marcha/fisiologia
4.
Sensors (Basel) ; 24(19)2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39409369

RESUMO

Pathological gait in patients with Hakim's disease (HD, synonymous with idiopathic normal-pressure hydrocephalus; iNPH), Parkinson's disease (PD), and cervical myelopathy (CM) has been subjectively evaluated in this study. We quantified the characteristics of upper and lower limb movements in patients with pathological gait. We analyzed 1491 measurements of 1 m diameter circular walking from 122, 12, and 93 patients with HD, PD, and CM, respectively, and 200 healthy volunteers using the Three-Dimensional Pose Tracker for Gait Test. Upper and lower limb movements of 2D coordinates projected onto body axis sections were derived from estimated 3D relative coordinates. The hip and knee joint angle ranges on the sagittal plane were significantly smaller in the following order: healthy > CM > PD > HD, whereas the shoulder and elbow joint angle ranges were significantly smaller, as follows: healthy > CM > HD > PD. The outward shift of the leg on the axial plane was significantly greater, as follows: healthy < CM < PD < HD, whereas the outward shift of the upper limb followed the order of healthy > CM > HD > PD. The strongest correlation between the upper and lower limb movements was identified in the angle ranges of the hip and elbow joints on the sagittal plane. The lower and upper limb movements during circular walking were correlated. Patients with HD and PD exhibited reduced back-and-forth swings of the upper and lower limbs.


Assuntos
Análise da Marcha , Marcha , Extremidade Inferior , Doença de Parkinson , Extremidade Superior , Humanos , Masculino , Feminino , Extremidade Inferior/fisiopatologia , Análise da Marcha/métodos , Idoso , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Doença de Parkinson/diagnóstico , Marcha/fisiologia , Extremidade Superior/fisiopatologia , Movimento/fisiologia , Caminhada/fisiologia , Fenômenos Biomecânicos/fisiologia , Hidrocefalia de Pressão Normal/fisiopatologia , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/diagnóstico , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/diagnóstico , Adulto
5.
BMC Musculoskelet Disord ; 24(1): 706, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670304

RESUMO

BACKGROUND: Gait decline in older adults is related to falling risk, some of which contribute to injurious falls requiring medical attention or restriction of activity of daily living. Among injurious falls, distal radius fracture (DRF) is a common initial fragility fracture associated with the subsequent fracture risk in postmenopausal females. The recent invention of an inertial measurement unit (IMU) facilitates the assessment of free-living gait; however, little is known about the daily gait characteristics related to the risk of subsequent fractures. We hypothesized that females with DRF might have early changes in foot kinematics in daily gait. The aim of this study was to evaluate the daily-life gait characteristics related to the risk of falls and fracture. METHODS: In this cross-sectional study, we recruited 27 postmenopausal females with DRF as their first fragility fracture and 28 age-matched females without a history of fragility fractures. The participants underwent daily gait assessments for several weeks using in-shoe IMU sensors. Eight gait parameters and each coefficient of variance were calculated. Some physical tests, such as hand grip strength and Timed Up and Go tests, were performed to check the baseline functional ability. RESULTS: The fracture group showed lower foot angles of dorsiflexion and plantarflexion in the swing phase. The receiver operating characteristic curve analyses revealed that a total foot movement angle (TFMA) < 99.0 degrees was the risk of subsequent fracture. CONCLUSIONS: We extracted the daily-life gait characteristics of patients with DRF using in-shoe IMU sensors. A lower foot angle in the swing phase, TFMA, may be associated with the risk of subsequent fractures, which may be effective in evaluating future fracture risk. Further studies to predict and prevent subsequent fractures from daily-life gait are warranted.


Assuntos
Fraturas Ósseas , Fraturas do Punho , Humanos , Feminino , Idoso , Estudos Transversais , Força da Mão , Pós-Menopausa , Marcha
6.
Sensors (Basel) ; 23(13)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37448065

RESUMO

Distinguishing pathological gait is challenging in neurology because of the difficulty of capturing total body movement and its analysis. We aimed to obtain a convenient recording with an iPhone and establish an algorithm based on deep learning. From May 2021 to November 2022 at Yamagata University Hospital, Shiga University, and Takahata Town, patients with idiopathic normal pressure hydrocephalus (n = 48), Parkinson's disease (n = 21), and other neuromuscular diseases (n = 45) comprised the pathological gait group (n = 114), and the control group consisted of 160 healthy volunteers. iPhone application TDPT-GT captured the subjects walking in a circular path of about 1 meter in diameter, a markerless motion capture system, with an iPhone camera, which generated the three-axis 30 frames per second (fps) relative coordinates of 27 body points. A light gradient boosting machine (Light GBM) with stratified k-fold cross-validation (k = 5) was applied for gait collection for about 1 min per person. The median ability model tested 200 frames of each person's data for its distinction capability, which resulted in the area under a curve of 0.719. The pathological gait captured by the iPhone could be distinguished by artificial intelligence.


Assuntos
Inteligência Artificial , Captura de Movimento , Humanos , Marcha , Caminhada , Algoritmos , Fenômenos Biomecânicos , Movimento (Física)
7.
Sensors (Basel) ; 23(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36679412

RESUMO

To assess pathological gaits quantitatively, three-dimensional coordinates estimated with a deep learning model were converted into body axis plane projections. First, 15 healthy volunteers performed four gait patterns; that is, normal, shuffling, short-stepped, and wide-based gaits, with the Three-Dimensional Pose Tracker for Gait Test (TDPT-GT) application. Second, gaits of 47 patients with idiopathic normal pressure hydrocephalus (iNPH) and 92 healthy elderly individuals in the Takahata cohort were assessed with the TDPT-GT. Two-dimensional relative coordinates were calculated from the three-dimensional coordinates by projecting the sagittal, coronal, and axial planes. Indices of the two-dimensional relative coordinates associated with a pathological gait were comprehensively explored. The candidate indices for the shuffling gait were the angle range of the hip joint < 30° and relative vertical amplitude of the heel < 0.1 on the sagittal projection plane. For the short-stepped gait, the angle range of the knee joint < 45° on the sagittal projection plane was a candidate index. The candidate index for the wide-based gait was the leg outward shift > 0.1 on the axial projection plane. In conclusion, the two-dimensional coordinates on the body axis projection planes calculated from the 3D relative coordinates estimated by the TDPT-GT application enabled the quantification of pathological gait features.


Assuntos
Aprendizado Profundo , Aplicativos Móveis , Humanos , Idoso , Marcha , Articulação do Joelho , Articulação do Quadril , Fenômenos Biomecânicos
8.
Sensors (Basel) ; 23(22)2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-38005649

RESUMO

We aimed to capture the fluctuations in the dynamics of body positions and find the characteristics of them in patients with idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease (PD). With the motion-capture application (TDPT-GT) generating 30 Hz coordinates at 27 points on the body, walking in a circle 1 m in diameter was recorded for 23 of iNPH, 23 of PD, and 92 controls. For 128 frames of calculated distances from the navel to the other points, after the Fourier transforms, the slopes (the representatives of fractality) were obtained from the graph plotting the power spectral density against the frequency in log-log coordinates. Differences in the average slopes were tested by one-way ANOVA and multiple comparisons between every two groups. A decrease in the absolute slope value indicates a departure from the 1/f noise characteristic observed in healthy variations. Significant differences in the patient groups and controls were found in all body positions, where patients always showed smaller absolute values. Our system could measure the whole body's movement and temporal variations during walking. The impaired fluctuations of body movement in the upper and lower body may contribute to gait and balance disorders in patients.


Assuntos
Hidrocefalia de Pressão Normal , Doença de Parkinson , Humanos , Captura de Movimento , Smartphone , Caminhada , Marcha
9.
Epilepsy Behav ; 129: 108614, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35203014

RESUMO

PURPOSE: The relationship between treatment efficacy/tolerability and the dose/blood concentration of lacosamide (LCM) was investigated in a clinical cohort of Japanese pediatric patients with epilepsy. METHODS: This retrospective analysis reviewed the medical records of patients treated with LCM for >6 months at the Department of Pediatrics, Hiroshima University Hospital, from September 2017 to January 2021. The collected data included age, sex, epilepsy type, seizure type, seizure frequency before and after treatment initiation, adverse events leading to LCM discontinuation, dose at any evaluation point, serum concentration, and concomitant antiepileptic drugs (AEDs). RESULTS: The study included 51 patients (31 male patients) between the ages of 2 and 19 years. All patients were Japanese. Epilepsy was classified as focal in 44 patients, generalized in six patients, and combined generalized and focal in one patient. The 50% responder rate for LCM treatment was 56.9%. Seven patients experienced complete seizure control (absence of seizures for 6 months before the follow-up visit). A relationship between dose and blood concentration was identified. Although the blood LCM concentration was higher in the responders than in the nonresponders (7.86 vs. 6.16 µg/mL; p = 0.028), there was no significant difference in dose between the two groups. Lacosamide showed efficacy at a dose >5 mg/kg/day in more than half of the 50% responders. The treatment-emergent adverse events (TEAEs) included seizure aggravation in five patients, irritability in two patients, and somnolence and drug eruption in one patient each. In six patients with TEAEs, the TEAEs developed within 1 month after treatment initiation and led to LCM discontinuation. CONCLUSION: In Japanese pediatric patients with epilepsy, LCM treatment is effective, particularly at higher doses. The blood concentration may be related more to efficacy than to dose. Lacosamide is generally well-tolerated by pediatric patients, and should be used at the maximum tolerable dose (needed to be gradually increased) in patients with otherwise insufficient seizure control. As TEAEs leading to discontinue treatment likely occur in early phase, it is needed to monitor patients carefully if TEAEs would happen in that phase.


Assuntos
Epilepsias Parciais , Epilepsia , Acetamidas/efeitos adversos , Adolescente , Anticonvulsivantes/sangue , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Epilepsias Parciais/tratamento farmacológico , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Feminino , Humanos , Japão , Lacosamida/sangue , Lacosamida/uso terapêutico , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Sensors (Basel) ; 22(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35161674

RESUMO

In a previous study, we developed a classification model to detect fall risk for elderly adults with a history of falls (fallers) using micro-Doppler radar (MDR) gait measurements via simulation. The objective was to create daily monitoring systems that can identify elderly people with a high risk of falls. This study aimed to verify the effectiveness of our model by collecting actual MDR data from community-dwelling elderly people. First, MDR gait measurements were performed in a community setting, and the efficient gait parameters for the classification of fallers were extracted. Then, a support vector machine model that was trained and validated using the simulated MDR data was tested for the gait parameters extracted from the actual MDR data. A classification accuracy of 78.8% was achieved for the actual MDR data. The validity of the experimental results was confirmed based on a comparison with the results of our previous simulation study. Thus, the practicality of the faller classification model constructed using the simulated MDR data was verified for the actual MDR data.


Assuntos
Vida Independente , Radar , Acidentes por Quedas , Adulto , Idoso , Marcha , Humanos , Máquina de Vetores de Suporte
11.
Sensors (Basel) ; 22(14)2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35890959

RESUMO

To quantitatively assess pathological gait, we developed a novel smartphone application for full-body human motion tracking in real time from markerless video-based images using a smartphone monocular camera and deep learning. As training data for deep learning, the original three-dimensional (3D) dataset comprising more than 1 million captured images from the 3D motion of 90 humanoid characters and the two-dimensional dataset of COCO 2017 were prepared. The 3D heatmap offset data consisting of 28 × 28 × 28 blocks with three red-green-blue colors at the 24 key points of the entire body motion were learned using the convolutional neural network, modified ResNet34. At each key point, the hottest spot deviating from the center of the cell was learned using the tanh function. Our new iOS application could detect the relative tri-axial coordinates of the 24 whole-body key points centered on the navel in real time without any markers for motion capture. By using the relative coordinates, the 3D angles of the neck, lumbar, bilateral hip, knee, and ankle joints were estimated. Any human motion could be quantitatively and easily assessed using a new smartphone application named Three-Dimensional Pose Tracker for Gait Test (TDPT-GT) without any body markers or multipoint cameras.


Assuntos
Aprendizado Profundo , Fenômenos Biomecânicos , Marcha , Humanos , Movimento (Física) , Smartphone
12.
J Clin Immunol ; 41(1): 125-135, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33083971

RESUMO

IRAK4 deficiency is an inborn error of immunity predisposing patients to invasive pyogenic infections. Currently, there is no established simple assay that enables precise characterization of IRAK4 mutant alleles in isolation. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune condition that is characterized by psychiatric symptoms, involuntary movement, seizures, autonomic dysfunction, and central hypoventilation. It typically occurs in adult females associated with tumors. Only a few infantile cases with anti-NMDAR encephalitis have been so far reported. We identified a 10-month-old boy with IRAK4 deficiency presenting with anti-NMDAR encephalitis and human herpes virus 6 (HHV6) reactivation. The diagnosis of IRAK4 deficiency was confirmed by the identification of compound heterozygous mutations c.29_30delAT (p.Y10Cfs*9) and c.35G>C (p.R12P) in the IRAK4 gene, low levels of IRAK4 protein expression in peripheral blood, and defective fibroblastic cell responses to TLR and IL-1 (TIR) agonist. We established a novel NF-κB reporter assay using IRAK4-null HEK293T, which enabled the precise evaluation of IRAK4 mutations. Using this system, we confirmed that both novel mutations identified in the patient are deleterious. Our study provides a new simple and reliable method to analyze IRAK4 mutant alleles. It also suggests the possible link between inborn errors of immunity and early onset anti-NMDAR encephalitis.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Herpesvirus Humano 6/fisiologia , Doenças da Imunodeficiência Primária/diagnóstico , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/virologia , Ativação Viral , Alelos , Encefalite Antirreceptor de N-Metil-D-Aspartato/etiologia , Autoimunidade , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Análise Mutacional de DNA , Diagnóstico Diferencial , Gerenciamento Clínico , Suscetibilidade a Doenças , Genes Reporter , Predisposição Genética para Doença , Células HEK293 , Humanos , Lactente , Quinases Associadas a Receptores de Interleucina-1/imunologia , Imageamento por Ressonância Magnética , Masculino , Mutação , Linhagem , Doenças da Imunodeficiência Primária/imunologia , Avaliação de Sintomas
13.
Environ Res ; 196: 110363, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33148423

RESUMO

The soil adsorption coefficient (Koc) is an environmental fate parameter that is essential for environmental risk assessment. However, obtaining Koc requires a significant amount of time and enormous expenditure. Thus, it is necessary to efficiently estimate Koc in the early stages of a chemical's development. In this study, a quantitative structure-property relationship (QSPR) model was developed using calculated physicochemical properties and molecular descriptors with the OPEn structure-activity/property Relationship App (OPERA) and Mordred software using the largest available Koc dataset. Specifically, we compared the accuracies of the model using the light gradient boosted machine (LightGBM), a gradient boosting decision tree (GBDT) algorithm, with those of previous models. The experimental results suggested the potential to develop a QSPR model that will produce highly accurate Koc values using molecular descriptors and physicochemical properties. Unlike previous studies, the use of a combination of LightGBM, OPERA and Mordred enables the prediction of Koc for many chemicals with high accuracy. In this study, OPERA was used to calculate the physicochemical properties, and Mordred was used to calculate molecular descriptors. The wide range of chemicals covered by OPERA and Mordred enables the analysis of a diverse range of chemical compounds. We also report a method to tune the LightBGM program. The use of fast-processing software, such as LightGBM, enables parameter tuning of a method required to obtain best performance. Our research represents one of the few studies in the field of environmental chemistry to use LightGBM. Using physicochemical properties as well as molecular descriptors, we could develop highly accurate Koc prediction models when compared to prior studies. In addition, our QSPR models may be useful for preliminary environmental risk assessment without incurring significant costs during the early chemical developmental stage.


Assuntos
Poluentes do Solo , Solo , Adsorção , Algoritmos , Aprendizado de Máquina , Relação Quantitativa Estrutura-Atividade , Software
14.
BMC Geriatr ; 21(1): 417, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238238

RESUMO

BACKGROUND: Walking speed is an important measure associated with health outcomes in older individuals, such as dependency and death. This study aimed to examine whether the walking speed of community-dwelling older adults varies between time periods within a day, as measured outdoors in daily life. We aimed to determine the types of walking speed variations and examine the factors associated with them. METHODS: Daily life outdoor walking speed was measured in 92 participants (average age 71.9 years±5.64) using a GPS smartphone app for 1 month. Average walking speeds for five time periods were analyzed with a linear mixed model. Intra-day walking speed variation patterns were classified by latent class analysis. Factors associated with the class were identified by logistic regression analysis. RESULTS: A statistically significant difference in average walking speed was found between early morning (1.33 m/s), and afternoon (1.27 m/s) and evening (1.26 m/s) (p < 0.01). The intra-day variation in walking speed was attributed to variation in cadence. Two classes were identified: (1) fast walking speed with large variation and (2) slow walking speed with little variation; hypertension and frailty level were associated with the class. CONCLUSION: The results suggest that there is intra-day variation in walking speed in daily life, wherein the speed is the fastest early in the morning and slower in the afternoon and evening. A larger variation in the walking speed was related to the health status without hypertension or frailty. These results suggest that if a person shows less intra-day variation in walking speed, this could be a sign that they are susceptible to hypertension and an increased frailty level.


Assuntos
Fragilidade , Velocidade de Caminhada , Idoso , Nível de Saúde , Humanos , Vida Independente , Caminhada
15.
Graefes Arch Clin Exp Ophthalmol ; 258(4): 735-741, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31960130

RESUMO

PURPOSE: We evaluated changes in the numbers of microaneurysms (MAs) on fluorescein angiography (FA) and indocyanine green angiography (IA) in eyes with diabetic macular edema (DME) following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents. METHODS: Twenty-one eyes of 16 patients with DME were included in this retrospective study. All patients received an initial loading dose of three monthly injections of anti-VEGF agents; thereafter, they received a pro re nata regimen for at least 12 months of follow-up. FA and IA images were obtained before and at 6 months after the initial injection. RESULTS: The median numbers of MAs significantly decreased from six (interquartile range [IQR] 3-7) MAs in early-phase FA, three (IQR 3-5) leaky MAs in late-phase FA, and two (IQR 1-4) MAs in late-phase IA at baseline to two (IQR 1-3) MAs in early-phase FA, one (IQR 0-2) leaky MA in late-phase FA, and one (IQR 0-2) MA in late-phase IA at 6 months (P < 0.0001 for all). Only the median numbers of MAs in late-phase IA at baseline and at 6 months were significantly higher in the recurrent DME group (13 eyes) than in the non-recurrent DME group (five eyes) (three [IQR 2-4] vs one [IQR 1-2], one [IQR 0.5-2] vs zero [P = 0.0185 and P = 0.009]). CONCLUSION: Intravitreal injection of anti-VEGF agents reduced the numbers of MAs in patients with DME. The numbers of MAs detected by late-phase IA might be useful predictors of DME recurrence.


Assuntos
Retinopatia Diabética/complicações , Angiofluoresceinografia/métodos , Verde de Indocianina/farmacologia , Macula Lutea/diagnóstico por imagem , Edema Macular/diagnóstico , Microaneurisma/diagnóstico , Ranibizumab/administração & dosagem , Idoso , Inibidores da Angiogênese/administração & dosagem , Corantes/farmacologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Feminino , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Edema Macular/complicações , Edema Macular/tratamento farmacológico , Masculino , Microaneurisma/tratamento farmacológico , Microaneurisma/etiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual
16.
Bioorg Med Chem Lett ; 29(14): 1785-1790, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31101471

RESUMO

We report herein the synthesis and structure-activity relationships (SAR) of a series of pyridazine derivatives with the activation of glucose transporter type 4 (GLUT4) translocation. Through a cell-based phenotype screening in L6-GLUT4-myc myoblasts and functional glucose uptake assays, lead compound 1a was identified as a functional small molecule. After further derivatization, the thienopyridazine scaffold as the central ring (B-part) was revealed to have potent GLUT4 translocation activities. Consequently, we obtained promising compound 26b, which showed a significant blood glucose lowering effect in the severe diabetic mice model (10-week aged db/db mice) after oral dosing even at 10 mg/kg, implying that our pyridazine derivatives have potential to become novel therapeutic agents for diabetes mellitus.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Transportador de Glucose Tipo 4/metabolismo , Hipoglicemiantes/uso terapêutico , Piridazinas/uso terapêutico , Animais , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Estrutura Molecular , Piridazinas/farmacologia , Relação Estrutura-Atividade
17.
Neuropediatrics ; 50(3): 160-163, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30939600

RESUMO

PURPOSE: This study was aimed to assess the accurate incidence of renal stones in severely disabled children treated with topiramate (TPM). METHOD: We reviewed the medical records of severely disabled children with epilepsy under 15 years old who underwent radiological examinations to investigate urinary stones. The study enrolled 26 patients who were divided into two groups. One group had been treated with TPM for at least 1 year and the other had not been treated with TPM, zonisamide, acetazolamide, or other diuretic drugs. We collected parameters from the medical records and compared the groups. RESULTS: All participants were evaluated radiologically, with computed tomography (CT) in two patients, ultrasonography in 22 patients, and both in two. No patient had any morphological abnormality of the kidneys and history of urinary tract infection. There were no significant differences in sex, age, body weight, or feeding manner between the groups, while the incidence of renal stones or calcifications was significantly higher in the TPM-treated group (60 vs. 0%; p = 0.00241). CONCLUSION: There is a high incidence of renal stone formation in severely disabled children treated with TPM.


Assuntos
Anticonvulsivantes/efeitos adversos , Crianças com Deficiência , Epilepsia/tratamento farmacológico , Cálculos Renais/induzido quimicamente , Índice de Gravidade de Doença , Topiramato/efeitos adversos , Adolescente , Criança , Pré-Escolar , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Feminino , Humanos , Incidência , Cálculos Renais/diagnóstico , Cálculos Renais/epidemiologia , Masculino , Estudos Retrospectivos
18.
Epilepsy Behav ; 94: 82-86, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30897534

RESUMO

BACKGROUND: Perampanel (PER) is a new antiepileptic drug (AED) with a novel mechanism of action. Investigations of the efficacy and safety of PER in pediatric and adult patients have increased recently. Although the clinical usefulness and pharmacokinetics of PER have been investigated in adolescent and adult populations, similar studies have not been performed in children. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients treated with PER for more than 6 months in the Department of Pediatrics, Hiroshima University Hospital, between September 2016 and November 2018. We obtained demographic and clinical data including age, sex, epilepsy type, seizure type, seizure frequency before and after treatment initiation, adverse events, reasons for discontinuing PER treatment, doses at evaluation points, serum concentrations, concomitant AEDs, intellectual status, and epilepsy etiology. Seizure types and epilepsy syndromes were classified according to the criteria of the International League Against Epilepsy. RESULTS: The study included 44 patients (22 males) between the ages of 6 months and 16 years. Of those, 10 patients discontinued PER therapy. The 50% response rate was 52.3% in patients treated with PER, and four patients achieved complete seizure control. Perampanel was highly effective in patients with generalized and focal epilepsy (50% responder rates, 52.9% and 50.0%, respectively). Favorable response rates were observed for tonic-clonic, focal nonmotor, and absence seizures with 50% response rates of 54.5%, 50.0%, and 66.7%, respectively. The 50% responder rate was 31.3 for epileptic spasms (ES). Treatment-emergent adverse events (TEAEs) included somnolence (n = 8), irritability (n = 2), ataxia (n = 2), and one case each of dizziness, compulsiveness, and enuresis. Serum concentrations of PER were compared in patients taking concomitant enzyme-inducing antiepileptic drugs (EIAEDs; carbamazepine, phenytoin, and phenobarbital) and those taking concomitant non-EIAEDs. Serum PER concentrations were correlated with dose per body weight in both groups (EIAED: r = 0.765, p = 0.00000212; non-EIAED: r = 0.71, p = 0.0000158). The mean concentration-to-dose (CD) ratio was 2398.4 ng mL-1 mg-1 kg-1 (range: 800-4524.7) in the non-EIAED group and 693.7 ng mL-1 mg-1 kg-1 (range: 344-1309.7) in the EIAED group. Serum PER levels were lower in the EIAED group than in the non-EIAED group. All patients with serum PER concentrations above 400 ng/mL experienced somnolence. CONCLUSIONS: Perampanel is effective against various types of seizures, including ES, in pediatric patients with refractory epilepsy. Furthermore, PER has good tolerability when the dose is adjusted based on serum concentrations. The PER CD ratio was lower in pediatric patients than in adolescents and adults; therefore, clinicians must consider the CD ratio when treating children with PER.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsias Parciais/tratamento farmacológico , Epilepsia Tipo Ausência/tratamento farmacológico , Piridonas/uso terapêutico , Adolescente , Anticonvulsivantes/sangue , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , Tontura/induzido quimicamente , Quimioterapia Combinada , Feminino , Humanos , Lactente , Masculino , Nitrilas , Fenobarbital/uso terapêutico , Fenitoína/uso terapêutico , Piridonas/sangue , Estudos Retrospectivos , Resultado do Tratamento
19.
Int J Clin Oncol ; 24(3): 328-333, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30368627

RESUMO

BACKGROUND: In recent years, the incidence of malignant disease in pregnancy has been increasing, but there are few large-scale surveys of malignant disease in pregnancy in Japan. The aim of this study was to survey malignant disease occurring during pregnancy in Japan. METHODS: Malignant disease in pregnancy was defined as diagnosis or treatment for malignant disease, except in situ carcinoma during pregnancy, or within 1-year postpartum. First, a primary survey questionnaire of the incidence of malignant disease in pregnancy and the number of deliveries over the course of 2014 was sent to 510 medical centers in Japan. Second, the survey questionnaires on the incidence of malignant diseases in pregnancy were collected and analyzed in detail. RESULTS: Of the 510 medical centers, 411 (81%) responded to the survey. There were 215,372 deliveries and 189 incidents (0.09%) of malignant disease in pregnancy. Of the 189 patients with malignancy, 157 detailed responses about the patients were received. The most frequently encountered cancer types were cervical cancer (36%), breast cancer (24%), and ovarian cancer (15%). During the 2 years after delivery, 15 patients (1 with breast cancer, 2 with ovarian cancer, 3 with hematologic malignancy, 4 with intestinal cancer, and 5 with others) died of the disease; most of them had advanced disease. In particular, 88% of the patients with intestinal cancers at diagnosis had advanced disease, and half of them died of disease. CONCLUSIONS: In Japan, the most common malignancies in pregnancy in order of frequency are cervical cancer, breast cancer, and ovarian cancer. Early diagnosis and appropriate management of cancer during pregnancy are important for improving maternal and neonatal outcomes, because advanced diseases have a poor prognosis.


Assuntos
Complicações Neoplásicas na Gravidez/epidemiologia , Adulto , Neoplasias da Mama/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Neoplasias Intestinais/epidemiologia , Japão/epidemiologia , Neoplasias Ovarianas/epidemiologia , Período Pós-Parto , Gravidez , Neoplasias do Colo do Útero/epidemiologia
20.
Eur J Appl Physiol ; 119(1): 85-90, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30298456

RESUMO

PURPOSE: Although sprinters with unilateral (UTF) and bilateral transfemoral (BTF) amputations and functional impairments (FIs) without amputation were allocated into different classifications because of the recent revision of the International Paralympic Committee Athletics Rules and Regulations, it is unclear whether running mechanics differ among the three groups. The aim of this study was to investigate the differences in the spatiotemporal parameters of the three groups during 100-m sprint in official competitions. METHODS: Using publicly available Internet broadcasts, we analyzed 11 elite-level sprinters with UTF amputation, 4 sprinters with BTF amputation, and 5 sprinters with FI without amputation. The best personal times for nearly all individuals were included. For each sprinter's race, the average speed, step frequency, and step length were calculated using the number of steps in conjunction with the official race time. RESULTS: Although there were no significant differences in the average speed among the UTF, BTF, and FI groups (7.95 ± 0.22, 7.90 ± 0.42, and 7.93 ± 0.14 m/s, respectively, p = 0.87), those with BTF amputation showed significantly lower step frequency (UTF: 4.20 ± 0.20 Hz, BTF: 3.71 ± 0.32 Hz, FI: 4.20 ± 0.10 Hz, p < 0.05) and longer step length (UTF: 1.90 ± 0.08 m, BTF: 2.14 ± 0.02 m, FI: 1.89 ± 0.06 m, p < 0.05) than the other two groups. CONCLUSION: These results suggest that the step characteristics during sprinting are not the same among sprinters with UTF amputation, BTF amputations, or FI without amputations.


Assuntos
Amputados/classificação , Desempenho Atlético , Corrida , Membros Artificiais , Atletas , Fenômenos Biomecânicos , Humanos , Gravação em Vídeo
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