Setagaya ku, Japan
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Tanihara H.,Kumamoto University | Inoue T.,Kumamoto University | Yamamoto T.,Gifu University | Kuwayama Y.,Fukushima Eye Clinic | And 2 more authors.
American Journal of Ophthalmology | Year: 2013

Purpose: To identify the optimal dose of a novel Rho kinase inhibitor, K-115, by assessing dose dependency of the intraocular pressure (IOP)-lowering effects and the safety in patients with primary open-angle glaucoma or ocular hypertension. Designs: Multicenter, prospective, randomized, placebo-controlled, double-masked, parallel group comparison clinical study. Methods: After appropriate washout periods, 210 patients with primary open-angle glaucoma or ocular hypertension were subdivided into 4 groups and were treated with K-115 in concentrations of 0.1%, 0.2%, and 0.4% or placebo twice daily for 8 weeks. The dose response of IOP reduction and the incidence of adverse events by K-115 or placebo were investigated. Results: The mean baseline IOP was between 23.0 and 23.4 mm Hg. The mean IOP reductions of the last visit from baseline were -2.2 mm Hg, -3.4 mm Hg, -3.2 mm Hg, and -3.5 mm Hg, respectively, in the placebo, 0.1%, 0.2%, and 0.4% groups at before instillation (9:00); -2.5 mm Hg, -3.7 mm Hg, -4.2 mm Hg, and -4.5 mm Hg at 2 hours after instillation (11:00); and -1.9 mm Hg, -3.2 mm Hg, -2.7 mm Hg, and -3.1 mm Hg at 8 hours after instillation (17:00). The dose-dependent IOP-lowering effect of K-115 was statistically significant at all time points. Also, conjunctival hyperemia was found in 7 (13.0%) of 54 patients for placebo, 23 (43.4%) of 53 patients for the 0.1% group, 31 (57.4%) of 54 patients for the 0.2% group, and 32 (65.3%) of 49 patients for the 0.4% group. Conclusions: On the basis of this dose-response study, K-115 0.4% has been selected to be the optimal dose and has the potential to be a promising new agent for glaucoma to control 24-hour IOP by twice-daily dosing.


Wakabayashi K.,Hirosaki University | Mori F.,Hirosaki University | Tanji K.,Hirosaki University | Orimo S.,Kanto Central Hospital | Takahashi H.,Niigata University
Acta Neuropathologica | Year: 2010

Involvement of the peripheral nervous system (PNS) is relatively common in some neurodegenerative proteinopathies of the brain and may be pathogenetically and diagnostically important. In Parkinson's disease, neuronal α-synuclein aggregates are distributed throughout the nervous system, including the central nervous system (CNS), sympathetic ganglia, enteric nervous system, cardiac and pelvic plexuses, submandibular gland, adrenal medulla and skin. The pathological process may target the PNS and CNS at the same time. In multiple system atrophy, numerous glial cytoplasmic inclusions composed of filamentous α-synuclein are widely distributed in the CNS, while α-synuclein accumulation is minimal in the sympathetic ganglia and is restricted to neurons. Neurofibrillary tangles can occur in the sympathetic and spinal ganglia in tauopathy, although they appear to develop independently of cerebral Alzheimer's disease pathology. In amyotrophic lateral sclerosis, neuronal loss with TDP-43-positive neuronal cytoplasmic inclusions in the spinal ganglia is more frequent than previously thought. Peripheral ganglia and visceral organs are also involved in polyglutamine diseases. Further elucidation and characterization of PNS lesions will have implications for intravital biopsy diagnosis in neurodegenerative proteinopathy, particularly in Parkinson's disease. © 2010 Springer-Verlag.


Hove M.J.,Tokyo Institute of Technology | Hove M.J.,Max Planck Institute for Human Cognitive and Brain Sciences | Suzuki K.,Tokyo Institute of Technology | Uchitomi H.,Tokyo Institute of Technology | And 2 more authors.
PLoS ONE | Year: 2012

Parkinson's disease (PD) and basal ganglia dysfunction impair movement timing, which leads to gait instability and falls. Parkinsonian gait consists of random, disconnected stride times-rather than the 1/f structure observed in healthy gait-and this randomness of stride times (low fractal scaling) predicts falling. Walking with fixed-tempo Rhythmic Auditory Stimulation (RAS) can improve many aspects of gait timing; however, it lowers fractal scaling (away from healthy 1/f structure) and requires attention. Here we show that interactive rhythmic auditory stimulation reestablishes healthy gait dynamics in PD patients. In the experiment, PD patients and healthy participants walked with a) no auditory stimulation, b) fixed-tempo RAS, and c) interactive rhythmic auditory stimulation. The interactive system used foot sensors and nonlinear oscillators to track and mutually entrain with the human's step timing. Patients consistently synchronized with the interactive system, their fractal scaling returned to levels of healthy participants, and their gait felt more stable to them. Patients and healthy participants rarely synchronized with fixed-tempo RAS, and when they did synchronize their fractal scaling declined from healthy 1/f levels. Five minutes after removing the interactive rhythmic stimulation, the PD patients' gait retained high fractal scaling, suggesting that the interaction stabilized the internal rhythm generating system and reintegrated timing networks. The experiment demonstrates that complex interaction is important in the (re)emergence of 1/f structure in human behavior and that interactive rhythmic auditory stimulation is a promising therapeutic tool for improving gait of PD patients. © 2012 Hove et al.


Orimo S.,Kanto Central Hospital | Suzuki M.,Jikei University School of Medicine | Inaba A.,Kanto Central Hospital | Mizusawa H.,Tokyo Medical and Dental University
Parkinsonism and Related Disorders | Year: 2012

Objectives: Differential diagnosis of Parkinson's disease (PD) and other neurodegenerative parkinsonism by clinical consensus criteria and diagnostic imaging is often difficult. 123I-meta-iodobenzylguanidine ( 123I-MIBG) myocardial scintigraphy is a useful imaging tool for differentiating PD from other parkinsonism. The purpose of the present study is to systematically review and perform a meta-analysis of studies on the diagnostic performance of 123I-MIBG myocardial scintigraphy for the differential diagnosis of PD and other neurodegenerative parkinsonism, specifically multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Methods: A computer literature search of the PubMED/MEDLINE database was conducted to find relevant published articles on 123I-MIBG myocardial scintigraphy for the differential diagnosis of PD and other neurodegenerative parkinsonism. We used the bivariate random-effects model to obtain the pooled estimates of the sensitivity and specificity and the corresponding 95% confidence intervals. Results: Thirteen studies comprising 845 patients including 625 PD and 220 other neurodegenerative parkinsonism were analyzed. The pooled sensitivity and specificity to differentiate PD from other neurodegenerative parkinsonism by the early heart-to-mediastinum (H/M) ratio were 82.6% and 89.2%, respectively, and those by the delayed H/M ratio were 89.7% and 82.6%, respectively. When PD was limited to early stage (Hoehn-Yahr stage 1 or 2), the pooled sensitivity and specificity by the delayed H/M ratio were 94.1% and 80.2%, respectively. Conclusions: The present meta-analysis confirmed high sensitivity and specificity of 123I-MIBG myocardial scintigraphy for differentiating PD from other neurodegenerative parkinsonism in both early and delayed imaging phases. Furthermore, 123I-MIBG myocardial scintigraphy was highly effective for distinguishing early PD. © 2012 Elsevier Ltd.


Ishii S.,University of Tokyo | Miyao M.,Kanto Central Hospital | Mizuno Y.,Kanto Central Hospital | Tanaka-Ishikawa M.,Kanto Central Hospital | And 2 more authors.
Osteoporosis International | Year: 2014

Previous studies on the association between uric acid and bone mineral density yielded conflicting results. In this study, we demonstrated positive association between uric acid and lumbar spine bone mineral density in peri- and postmenopausal Japanese women. Further research is needed to elucidate the underlying mechanism. Introduction: Oxidative stress has been implicated in the pathogenesis of osteoporosis. Uric acid, a potent antioxidant substance, has been associated with bone mineral density but previous studies have yielded conflicting results. The objective of the study was to examine the association between serum uric acid and lumbar spine bone mineral density (BMD). Methods: This was a retrospective analysis of medical records of 615 women, aged 45-75 years, who had lumbar spine BMD measurement by dual-energy X-ray absorptiometry as a part of health checkup from August 2011 to July 2012. Results: Mean serum uric acid level was 4.7 mg/dL. Serum uric acid level was positively and significantly associated with lumbar spine BMD independent of age, body mass index, smoking, drinking, physical activity, years after menopause, diabetes mellitus, hypertension, serum calcium, estimated glomerular filtration rate, plasma C-reactive protein, and serum alkaline phosphatase (standardized beta = 0.078, p = 0.049). Uric acid rapidly increased until the age of 60 years, and then decelerated but continued to increase thereafter. The association between lumbar spine BMD and uric acid remained significantly positive after excluding women older than 60 years. Conclusion: The present study showed that higher uric acid levels were linearly associated with higher lumbar spine BMD in peri- and postmenopausal Japanese women. Further research is needed to elucidate the underlying mechanism of the association between uric acid and BMD. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.


Yoshitake S.,Kanto Central Hospital
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery | Year: 2013

Massive intrapulmonary haemorrhage and haemothorax are uncommon presentations associated with pulmonary sequestration. Here, we describe the case of a 40-year-old man who suffered from high fever and haemoptysis for 1 week before he was admitted to our hospital with a complaint of chest discomfort with shock. Computed tomography revealed that pulmonary sequestration supplied from the coeliac artery with persistent bleeding. The patient underwent right lower lobectomy and an emergent laparotomy for ligation of the aberrant artery. A pulmonary sequestration has a severe complication resulting in shock due to intrapulmonary haemorrhage and haemothorax. Accordingly, early resection of a sequestered lung should be the choice of the treatment in these cases.


Horie M.,Kanto Central Hospital
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society | Year: 2010

A 71-year-old man was admitted to Kanto Central Hospital with hemoptysis. He had had chronic sinusitis and deafness since childhood. Situs inversus, bronchiectasia, and diffuse panbronchiolitis had been also diagnosed at the age of 59. Chest computed tomography demonstrated a 5-cm mass in the anterior mediastinum as well as a 4-cm mass in the upper lobe of the right lung. A transbronchial lung biopsy of the right lung tumor revealed squamous cell carcinoma. Electron microscopic examination of the bronchial epithelial cilia revealed a total defect of both inner and outer dynein arms, leading to a diagnosis of primary ciliary dyskinesia. Biopsy of the mediastinal tumor was not performed. After concurrent chemoradiation therapy, the lung cancer decreased in size partial remission (PR) and the mediastinal tumor disappeared complete remission (CR). Later, a cavity formed in the tumor, where a Pseudomonas aeruginosa infection occurred. He died 1 year after the diagnosis of lung cancer was established. There have been 5 reported cases of Kartagener syndrome complicated with lung cancer, but to the best of our knowledge there have been no reports of Kartagener syndrome with mediastinal tumor.


Orimo S.,Kanto Central Hospital
Brain and Nerve | Year: 2012

Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy can assess postganglionic presynaptic cardiac sympathetic nerve endings. Reduced cardiac MIBG uptake on MIBG myocardial scintigraphy has been reported in patients with Parkinson disease (PD), dementia with Lewy bodies (DLB), pure autonomic failure (PAF), and familial PD linked to SNCA duplication. This imaging procedure is a sensitive diagnostic tool that might differentiate PD and DLB from other movement disorders from Alzheimer disease (AD). We recently reported cardiac sympathetic denervation in PD, DLB, PAF, and familial PD linked to SNCA duplication which accounts for the reduced cardiac MIBG uptake in these disorders. The patients with PD, DLB, PAF and familial PD linked to SNCA duplication have Lewy bodies in the nervous system, whereas patients with multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration, AD, and parkin-associated PD do not. However, in patients with MSA or PSP, cardiac sympathetic denervation was associated with the presence of Lewy bodies in the nervous system. Therefore, cardiac sympathetic denervation is closely related to the presence of Lewy bodies in the wide range of neurodegenerative processes. Thus, we conclude that reduced cardiac MIBG uptake is a potential biomarker for the presence of Lewy bodies in the nervous system. We infer that MIBG myocardial scintigraphy is a noninvasive tool for detecting Lewy bodies during life.


Orimo S.,Kanto Central Hospital
Brain and Nerve | Year: 2015

Kosaka and colleagues first reported dementia with Lewy bodies (DLB) in 1976. They have also established the concept of DLB. It is important to differentiate DLB from other dementia, especially Alzheimer disease (AD), because the medical treatment, management, and prognosis of DLB and AD are different. We have used several clinical features and imaging tools to differentiate between DLB and AD. With regard to clinical features, patients with DLB have relatively mild memory disturbances and fluctuating cognition. However, compared to patients with AD they have more severe disturbances of attention and executive, visuospatial functions, visual hallucination, depression, autonomic symptoms. In addition, they show the presence of REM sleep behavior disorder and idiopathic parkinsonism. On performing imaging analysis, patients with DLB showed milder atrophy in the medial temporal lobe on brain MRI, reduced occipital activity on SPECT or PET, reduced MIBG uptake on MIBG cardiac scintigraphy, and low dopamine transporter activity in the basal ganglia on SPECT or PET.


Uchitomi H.,Tokyo Institute of Technology | Ota L.,Tokyo Institute of Technology | Ogawa K.-i.,Tokyo Institute of Technology | Orimo S.,Kanto Central Hospital | Miyake Y.,Tokyo Institute of Technology
PLoS ONE | Year: 2013

To develop a method for cooperative human gait training, we investigated whether interactive rhythmic cues could improve the gait performance of Parkinson's disease patients. The interactive rhythmic cues ware generated based on the mutual entrainment between the patient's gait rhythms and the cue rhythms input to the patient while the patient walked. Previously, we found that the dynamic characteristics of stride interval fluctuation in Parkinson's disease patients were improved to a healthy 1/f fluctuation level using interactive rhythmic cues and that this effect was maintained in the short term. However, two problems remained in our previous study. First, it was not clear whether the key factor underpinning the effect was the mutual entrainment between the gait rhythms and the cue rhythms or the rhythmic cue fluctuation itself. Second, it was not clear whether or not the gait restoration was maintained longitudinally and was relearned after repeating the cue-based gait training. Thus, the present study clarified these issues using 32 patients who participated in a four-day experimental program. The patients were assigned randomly to one of four experimental groups with the following rhythmic cues: (a) interactive rhythmic cue, (b) fixed tempo cue, (c) 1/f fluctuating tempo cue, and (d) no cue. It has been reported that the 1/f fluctuation of stride interval in healthy gait is absent in Parkinson's disease patients. Therefore, we used this dynamic characteristic as an evaluation index to analyze gait relearning in the four different conditions. We observed a significant effect in condition (a) that the gait fluctuation of the patients gradually returned to a healthy 1/f fluctuation level, whereas this did not occur in the other conditions. This result suggests that the mutual entrainment can facilitate gait relearning effectively. It is expected that interactive rhythmic cues will be widely applicable in the fields of rehabilitation and assistive technology. © 2013 Uchitomi et al.

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