Tokyo Metropolitan Geriatric Hospital

Tokyo, Japan

Tokyo Metropolitan Geriatric Hospital

Tokyo, Japan
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OBJECTIVE: We sought to identify clinicopathological characteristics of high-grade pancreatic intraepithelial neoplasia (PanIN)/carcinoma in situ to facilitate screening for pancreatic ductal adenocarcinoma. METHODS: We evaluated PanIN lesions in 173 consecutive autopsy cases with no evidence of pancreatic ductal adenocarcinoma and/or intraductal papillary mucinous neoplasm (mean age, 80.5 years) by submitting the entire pancreas for microscopic examination. RESULTS: PanIN-3 was found in 4% of examined cases, whereas PanIN-1 and PanIN-2 were present in 77% and 28%, respectively. PanIN-3 was more frequently identified in patients with diabetes mellitus and/or older age. PanIN-3 lesions were always multifocal, and the number of PanIN-3 foci was positively associated with those of PanIN-1 or PanIN-2. PanIN-3 was located more frequently in the pancreatic body and tail than in the head and predominantly involved small interlobular/intralobular ducts rather than the main duct. Notably, 71% of pancreata with PanIN-3 showed cystic changes in PanIN-3 and lower grade PanIN lesions. PanIN-3 was also accompanied by higher grade extralobular fibrosis. CONCLUSIONS: We found that 4% of the examined pancreata harbored PanIN-3 lesions that were associated with several unique clinicopathological features. The cystic change along with fibrotic pancreatic parenchyma may be detected by imaging studies such as endoscopic ultrasound. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Toba A.,Tokyo Metropolitan Geriatric Hospital
Blood Pressure Monitoring | Year: 2017

BACKGROUNDS: Orthostatic hypotension (OH) is associated with cardiovascular diseases, heart failure, and increased mortality. We evaluated whether OH was affected by cardiac structure and function or autonomic function in elderly hypertensive outpatients. PATIENTS AND METHODS: In 64 hypertension patients (mean age 74.2±1.7 years old), we evaluated changes in blood pressure (BP) and heart rate variability before and after standing up using the MemCalc system. In addition, we retrospectively reviewed their medical records and echocardiographic data. RESULTS: Of the total patients, 28% had OH [decrease of systolic blood pressure (SBP) ≥20 mmHg and/or diastolic BP ≥10 mmHg]. Multivariate linear regression analysis showed that stroke volume (SV)/pulse pressure (PP) was associated independently with orthostatic change in SBP (P=0.007). The patients with OH tended to have a lower SV (57.3±13.1 vs. 68.1±16.3 ml, P=0.009) and lower SV/PP (1.02±0.26 vs. 1.33±0.45, P=0.001) than those without OH. The significance in difference in SV/PP remained even after adjustment for age, sex, BMI, estimated glomerular filtration rate, number of antihypertesive drugs, history of diabetes, and SBP at rest (P=0.036). However, there were no significant differences in change in the low frequency/high frequency ratio after standing up (P=0.899) between patients with and without OH. CONCLUSION: Elderly hypertensive patients with OH may have a reduced arterial compliance, measured as SV/PP, and may not have differences in sympathetic nerve activities, measured as the low frequency/high frequency ratio. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Sakata R.,Tokyo Metropolitan Geriatric Hospital | Numaga J.,University of Tokyo
Clinical Interventions in Aging | Year: 2014

Background: To compare intraocular pressure (IOP) readings using the Icare rebound tonometer (RBT) versus the Goldmann applanation tonometer (GAT) in late elderly (aged 75 years or older) subjects with or without glaucoma, and to evaluate the influence of central corneal thickness (CCT) on IOP readings. Methods: The IOP measurements were obtained using the RBT and GAT, and CCT was measured using a specular-type microscope. Bland-Altman analysis was used to assess the clinical agreement between the two instruments. The influence of CCT adjusted for age on IOP readings was analyzed by multiple linear regression analysis. Results: This study included 58 eyes of 29 normal subjects and 54 eyes of 28 glaucoma patients. The mean age was 80.7±4.3 years (normal subjects) and 83.1±5.1 years (glaucoma patients). The mean IOP readings were 13.6±3.5 mmHg and 13.2±2.8 mmHg (using the RBT and GAT, respectively) for normal subjects, and13.6±3.3 mmHg and 13.5±2.9 mmHg for glaucoma patients. The 95% confidence interval of the differences between the two instruments was -3.3 to 4.0 mmHg for normal subjects and -2.9 to 1.6 mmHg for glaucoma patients. The IOP readings by two instruments were significantly correlated with CCT in eyes with glaucoma (for the RBT, β=0.036 and P=0.002, and for the GAT, β=0.021 and P=0.033) but not in normal eyes. Conclusion: IOP readings measured using the RBT and GAT showed within the allowable range in the late elderly subjects with or without glaucoma. Eyes with glaucoma were correlated closely with CCT using each instrument. © 2014 Sakata and Numaga.


Iriyama A.,Tokyo Metropolitan Geriatric Hospital | Iriyama A.,University of Tokyo | Aihara Y.,University of Tokyo | Yanagi Y.,University of Tokyo
Retina | Year: 2013

PURPOSE: To investigate the prevalence and characteristics of outer retinal tubulation (ORT) seen in inherited retinal degenerative diseases. METHODS: A total of 354 eyes of 177 patients were examined with spectral domain optical coherence tomography. One hundred and twelve patients had retinitis pigmentosa, 58 patients had cone dystrophy, and 7 patients had the Bietti crystalline dystrophy. The images obtained by horizontal and vertical scans were analyzed to explore the possible presence of ORT, estimate their prevalence, morphologic character, and their location in the retinal layers. RESULTS: With spectral domain optical coherence tomography, ORT was identified in 0 of 112 patients with retinitis pigmentosa, unilaterally in 3 of 58 patients with cone dystrophy, and bilaterally in 5 of 7 patients with the Bietti crystalline dystrophy. Outer retinal tubulation was detected under the fovea, and in the outer nuclear layer, ORT was detected in the Bietti crystalline dystrophy with a significantly higher frequency than in cone dystrophy (P < 0.001). CONCLUSION: There was a higher rate of ORT in the Bietti crystalline dystrophy among inherited retinal degenerative diseases. Copyright © Ophthalmic Communications Society, Inc.


Endo T.,Tokyo Metropolitan Geriatric Hospital
Journal of Biochemistry | Year: 2015

Most proteins are modified by glycans, which can modulate the biological properties and functions of glycoproteins. The major glycans can be classified into N-glycans and O-glycans according to their glycan-peptide linkage. This review will provide an overview of the O-mannosyl glycans, one subtype of O-glycans. Originally, O-mannosyl glycan was only known to be present on a limited number of glycoproteins, especially α-dystroglycan (α-DG). However, once a clear relationship was established between O-mannosyl glycan and the pathological mechanisms of some congenital muscular dystrophies in humans, research on the biochemistry and pathology of O-mannosyl glycans has been expanding. Because α-DG glycosylation is defective in congenital muscular dystrophies, which also feature abnormal neuronal migration, these disorders are collectively called α-dystroglycanopathies. In this article, I will describe the structure, biosynthesis and pathology of O-mannosyl glycans. © 2014 The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.


Sawabe M.,Tokyo Metropolitan Geriatric Hospital
Geriatrics and Gerontology International | Year: 2010

The large and medium-sized arteries in elderly people show varying degrees of intimal and medial change. The medial change is known as age-related medial degeneration and sclerosis (ARMDS). The ARMDS results in systolic hypertension and left ventricular hypertrophy of the heart as a result of loss of arterial elasticity. It also causes aortic dilatation, or even aortic aneurysm. The ARMDS and atherosclerosis are distinct entities, but are often overlapped and confused with each other. The present review mainly focuses on ARMDS and briefly addresses atherosclerosis, and aging of arterioles, capillaries and veins. The smooth muscle cells in the inner half of the aortic media of elderly people degenerate and undergo apoptosis. This causes degradation of elastin fibers and the accumulation of collagen fibers in the media, but the inflammatory infiltrates are scarce. Biochemical studies showed an age-related decrease of elastin and its crosslinks, and an increase of collagen and its crosslink. Because the turnover of elastin is very long, it likely suffers from glycation (Maillard reaction) and glyco-oxidative reaction. The advanced glycation end-products accumulate in the aortic media with increasing age. Alcian-blue positive mucin accumulates in aortic media in elderly people. The major component of the increase of aortic mucin is chondroitin-6-sulfate. Microcalcification is frequent in the inner acellular portion of the aortic media in elderly people. Calcium contents increase with age. In conclusion, the ARMDS is a distinct pathological entity with clinical significance. The pathogenesis of ARMDS is unclear; the mechanical stress of elastin, endothelial dysfunction, and glycation of elastin are proposed. © 2010 Japan Geriatrics Society.


The purpose of this study was to examine the association between objective measures of sleep quality and obesity in older community-dwelling people. This cross-sectional study included 189 community-dwelling adults aged ≥ 80 yr (83.4 ± 2.5 yr [age range, 80-95 yr]). Participants wore an accelerometer (ActiGraph GT3X+) on their non-dominant wrist 24 hr per day for 7 consecutive nights. Sleep parameters measured included total sleep time, sleep efficiency, and wake after sleep onset (WASO) during the night. Associations between sleep parameters and obesity were investigated by using multivariate logistic regression analysis. In multivariate models, those with sleep efficiency lower than 85% had a 2.85-fold increased odds of obesity, compared with those with sleep efficiency of 85% or higher. Similarly, those with WASO of ≥ 60 min (compared with < 60 min) had a 3.13-fold increased odds of obesity. However, there were no significant associations between total sleep time or self-reported napping duration and obesity. We found that poor sleep quality was an independent risk factor for obesity in community-dwelling Japanese adults aged ≥ 80 yr, even after controlling for potential confounding factors, including daily physical activity. © 2015 The Korean Academy of Medical Sciences.


Araki A.,Tokyo Metropolitan Geriatric Hospital
Nippon rinsho. Japanese journal of clinical medicine | Year: 2010

Insulin resistance in peripheral tissues has been suggested to have a crucial role for the pathogenesis of type 2 diabetes. Diabetic people had a 1.5 to 4 fold risk for Alzheimer disease as well as vascular dementia. The insulin resistance (i.e., hyperinsulinemia) in people with impaired glucose tolerance has been one of risk factors for cognitive decline as well as atherosclerotic disease. In contrast, impaired insulin signaling and insulin resistance in brain has been found to be important role for the pathogenesis of Alzheimer disease. Peripheral hyperinsulinemia may link to cerebral insulin resistance, leading to the inhibition of removal of amyloid beta protein and the increase of tau hyperphosphorylation. Several studies have shown that insulin sensitizers (pioglitazone and rosiglitazone) improve cognition and memory in patients with mild Alzheimer disease as well as animal model of Alzheimer disease. Therefore, insulin sensitizers may have one of the effective measures of the prevention of both types of dementia in people with diabetes mellitus.


Objective: This study aimed to examine the efficacy and safety of nepafenac ophthalmic suspension compared to placebo in the management of postoperative inflammation and ocular pain in Japanese patients undergoing cataract surgery. Methods: This was a multicenter, randomized, double-masked, placebo-controlled clinical study. Patients received nepafenac or placebo TID beginning 1 day before cataract surgery and continuing on the day of surgery for 14 days. One additional drop was administered on the day of surgery. The primary efficacy variables were the percentage of patients cured at postoperative day 14 visit (cure defined as aqueous cells score + aqueous flare score = 0) and the percentage of patients who were pain free at all postoperative visits. Results: The cure rate on day 14 after surgery was 71.4% (75/105) in the nepafenac group and 28.6% (30/105) in the placebo group, showing a significant difference in cure rate between groups. The nepafenac group demonstrated higher cure rates than those in the placebo group, with a significant difference in cure rate on days 7 and 14 postoperatively. The ocular pain-free rate was 96.2% (102/106) in the nepafenac group and 67.6% (71/105) in the placebo group, showing a significant difference between groups. Concerning adverse events (AEs), 26 AEs were reported in 21 subjects (19.6%) in the nepafenac group and 31 AEs were reported in 24 subjects (22.4%) in the placebo group. Conclusion: Nepafenac ophthalmic suspension is a nonsteroidal anti-inflammatory drug effective in the prevention of postoperative inflammation and ocular pain associated with cataract surgery. © 2011 The Author(s).


Kanemaru K.,Tokyo Metropolitan Geriatric Hospital
Brain and Nerve | Year: 2013

Aberrant protein aggregation is closely linked to the molecular pathogeneses of most neurodegenerative diseases. The major components of pathological aggregates have been characterized in various neurodegenerative diseases; for example, amyloid β-protein and phosphorylated tau in Alzheimer's disease, α-synuclein in Parkinson's disease, SOD1 or TDP-43 in amyotrophic lateral sclerosis, and huntingtin in Huntington's disease. These misfolded protein aggregates play a vital role in disease initiation and progression, and they have recently been shown to have prion-like spreading or seeded aggregation properties. Immunotherapy with specific monoclonal antibodies is a promising approach to clear misfolded protein aggregates and treat various neurodegenerative diseases; it is planned for use in clinical trials in the near future.

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