Juntendo Tokyo Koto Geriatric Medical Center

Tokyo, Japan

Juntendo Tokyo Koto Geriatric Medical Center

Tokyo, Japan
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Shimada K.,Juntendo University | Shimada K.,Juntendo Tokyo Koto Geriatric Medical Center | Motoi Y.,Juntendo University | Ishiguro K.,Juntendo University | And 10 more authors.
Neurobiology of Disease | Year: 2012

Lithium, a drug used to treat bipolar disorders, has a variety of neuroprotective mechanisms including inhibition of glycogen synthase kinase-3 (GSK-3), a major tau kinase. Recently, it has been shown that, in various neurodegenerative proteinopathies, lithium could induce autophagy. To analyze how lithium is therapeutically beneficial in tauopathies, transgenic mice overexpressing human mutant tau (P301L) were treated with oral lithium chloride (LiCl) for 4. months starting at the age of 5. months. At first, we examined the effects of treatment on behavior (using a battery of behavioral tests), tau phosphorylation (by biochemical assays), and number of neurofibrillary tangles (NFTs) (by immunohistopathology). In comparison with control mice, LiCl-treated mice showed a significantly better score in the sensory motor tasks, as well as decreases in tau phosphorylation, soluble tau level, and number of NFTs. Next, we examined lithium effects on autophagy using an antibody against microtubule-associated protein 1 light chain 3 (LC3) as an autophagosome marker. The number of LC3-positive autophagosome-like puncta was increased in neurons of LiCl-treated mice. Neurons containing NFTs were completely LC3-negative, whereas LC3-positive autophagosome-like puncta contained phosphorylated-tau (p-tau). The protein level of p62 was decreased in LiCl-treated mice. These data suggested that oral long-term lithium treatment could attenuate p-tau-induced motor disturbance not only by inhibiting GSK-3 but also by enhancing autophagy in tauopathy model mice. © 2012 Elsevier Inc.


Mita T.,Juntendo University | Katakami N.,Osaka University | Shiraiwa T.,Shiraiwa Medical Clinic | Yoshii H.,Juntendo Tokyo Koto Geriatric Medical Center | And 13 more authors.
Diabetes Care | Year: 2016

Objective The effect of additional treatment with oral hypoglycemic agents on the progression of atherosclerosis remains unknown in insulin-treated patients with type 2 diabetes mellitus (T2DM). We assessed the effects of sitagliptin, a dipeptidyl peptidase 4 inhibitor, on carotid intima-media thickness (IMT) in T2DM. Research Design and Methods This prospective, randomized, open-label, blinded end point, multicenter, parallelgroup, comparative study included 282 insulin-treated patients with T2DM free of a history of apparent cardiovascular diseases who were recruited at 12 clinical units and randomly allocated to either the sitagliptin group (n = 142) or the control group (n = 140). The primary outcomes were changes in mean and maximum IMT of the common carotid artery measured by echography at the end of a 104-week treatment period. Results Sitagliptin had a more potent glucose-lowering effect compared with the conventional treatment (20.5 ± 1.0% vs. 20.2 ± 0.9%; P = 0.004), without increasing hypoglycemic episodes or body weight. Changes in the mean and left maximum IMT, but not right maximum IMT, of the common carotid arteries were significantly greater after sitagliptin treatment compared with conventional treatment (20.029 [SE 0.013] vs. 0.024 [0.013] mm [P = 0.005]; 20.065 [0.027] vs. 0.022 [0.026] mm [P = 0.021]; 20.007 [0.031] vs. 0.027 [0.031] mm [P = 0.45], respectively). Over 104 weeks, sitagliptin, but not conventional treatment, significantly reduced the mean IMT and left maximumIMT of common carotid arteries relative to the baseline. Conclusions Sitagliptin attenuated the progression of carotid IMT in insulin-treated patients with T2DM free of apparent cardiovascular disease compared with conventional treatment. © 2016 by the American Diabetes Association.


Mita T.,Juntendo University | Katakami N.,Osaka University | Yoshii H.,Juntendo Tokyo Koto Geriatric Medical Center | Onuma T.,Juntendo Tokyo Koto Geriatric Medical Center | And 12 more authors.
Diabetes Care | Year: 2016

OBJECTIVE Recent experimental studies have shown that dipeptidyl peptidase 4 (DPP-4) inhibitors have antiatherosclerotic benefits in glucagon-like peptide 1-dependent and independentmanners. The current study investigated the effects of alogliptin, a DPP-4 inhibitor, on the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS This prospective, randomized, open-label, blinded-end point, multicenter, parallelgroup, comparative study included 341 patients with T2DM free of a history of apparent cardiovascular diseases recruited at 11 clinical units and randomly allocated to treatment with alogliptin (n = 172) or conventional treatment (n = 169). Primary outcomes were changes in mean common and maximum intima-media thickness (IMT) of the carotid artery measured by carotid arterial echography during a 24-month treatment period. RESULTS Alogliptin treatment had amore potent glucose-lowering effect than the conventional treatment (20.3 ± 0.7% vs. 20.1 ± 0.8%, P = 0.004) without an increase of hypoglycemia. Changes in the mean common and the right and left maximum IMT of the carotid arteries were significantly greater after alogliptin treatment than after conventional treatment (20.026 mm [SE 0.009] vs. 0.005 mm [SE 0.009], P = 0.022; 20.045 mm [SE 0.018] vs. 0.011 mm [SE 0.017], P = 0.025, and 20.079 mm [SE 0.018] vs. 20.015 mm [SE 0.018], P = 0.013, respectively). CONCLUSIONS Alogliptin treatment attenuated the progression of carotid IMT in patients with T2DM free of apparent cardiovascular disease compared with the conventional treatment. © 2016 by the American Diabetes Association.


PubMed | Juntendo University, Naka Memorial Clinic, Osaka General Medical Center, Osaka University and 5 more.
Type: | Journal: Scientific reports | Year: 2017

The effect of hypoglycemia on the progression of atherosclerosis in patients with type 2 diabetes mellitus (T2DM) remains largely unknown. This is a post hoc analysis of a randomized trial to investigate the relationship between hypoglycemic episodes and changes in carotid intima-media thickness (IMT). Among 274 study subjects, 104 patients experienced hypoglycemic episodes. Increases in the mean IMT and left maximum IMT of the common carotid arteries (CCA) were significantly greater in patients with hypoglycemia compared to those without hypoglycemia. Classification of the patients into three groups according to the frequency of hypoglycemic episodes showed that high frequency of hypoglycemic events was associated with increases in mean IMT-CCA, and left max-IMT-CCA and right max-IMT-CCA. In addition, repetitive episodes of hypoglycemia were associated with a reduction in the beneficial effects of sitagliptin on carotid IMT. Our data suggest that frequency of hypoglycemic episodes was associated with changes in carotid atherosclerosis.


Roberts C.B.,Access Economics Pty Ltd | Hiratsuka Y.,Juntendo Tokyo Koto Geriatric Medical Center | Yamada M.,Sensory Medical | Pezzullo M.L.,Access Economics Pty Ltd | And 4 more authors.
Archives of Ophthalmology | Year: 2010

Objective: To quantify the total economic cost of visual impairment in Japan. Methods: A prevalence-based approach was adopted using data on visual impairment, the national health system, and indirect costs to capture the economic impact of visual impairment in 2007. Results: In 2007, visual impairment affected more than 1.64 million people in Japan and cost around ¥8785.4 billion (US $72.8 billion) across the economy, equivalent to 1.7% of Japan's gross domestic product. The loss of well-being (years of life lost from disability and premature mortality) cost ¥5863.6 billion (US $48.6 billion). Direct health system costs were ¥1338.2 billion (US $11.1 billion). Other financial costs were ¥1583.5 billion (US $13.1 billion), including productivity losses, care takers' costs, and efficiency losses from welfare payments and taxes. Community care was the largest component of other financial costs and was composed of paid and unpaid services that provide home and personal care to people with visual impairment. The findings of this study are in line with those of similar studies in Australia and the United States. Conclusions: Visual impairment imposes substantial costs on society, particularly to individuals with visual impairment and their families. Eliminating or reducing disabilities from visual impairment through public awareness of preventive care, early diagnosis, more intensive disease treatment, and new medical technologies could significantly improve the quality of life for people with visual impairment and their families, while also potentially reducing national health care expenditure and increasing productivity in Japan. The results of this study should provide a first step in helping policymakers evaluate policy effects and to prioritize research expenditures. ©2010 American Medical Association. All rights reserved.


Takazawa T.,Gunma University | Mitsuhata H.,Juntendo Tokyo Koto Geriatric Medical Center | Mertes P.M.,Hopitaux Universitaires Of Strasbourg
Journal of Anesthesia | Year: 2016

Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common cause of anaphylaxis during anesthesia is reportedly neuromuscular blocking agents. Of the many muscle relaxants that are clinically available, rocuronium is becoming popular in many countries. Recent studies have demonstrated that succinylcholine (but also rocuronium use) is associated with a relatively high rate of IgE-mediated anaphylaxis compared with other muscle relaxant agents. Sugammadex is widely used for reversal of the effects of steroidal neuromuscular blocking agents, such as rocuronium and vecuronium. Confirmed cases of allergic reactions to clinical doses of sugammadex have also been recently reported. Given these circumstances, the number of cases of hypersensitivity to either sugammadex or rocuronium is likely to increase. Thus, anesthesiologists should be familiar with the epidemiology, mechanisms, and clinical presentations of anaphylaxis induced by these drugs. In this review, we focus on the diagnosis and treatment of anaphylaxis to sugammadex and neuromuscular blocking agents. Moreover, we discuss recent studies in this field, including the diagnostic utility of flow cytometry and improvement of rocuronium-induced anaphylaxis with the use of sugammadex. © 2015, The Author(s).


Suzuki Y.,Tsumura and Co. | Mitsuhata H.,Juntendo Tokyo Koto Geriatric Medical Center | Yuzurihara M.,Tsumura and Co. | Kase Y.,Tsumura and Co.
Evidence-based Complementary and Alternative Medicine | Year: 2012

Yokukansan, one of the traditional Japanese herbal medicines, ameliorated neuropathic pain symptoms in patients. In this study, we investigated the effects of yokukansan on neuropathic pain in chronic constriction injury (CCI) model. Oral administration of yokukansan significantly inhibited mechanical and cold allodynia in the von Frey hair or acetone test, respectively. In comparison, amitriptyline, a tricyclic antidepressant, demonstrated moderate, but not significant, antiallodynic effects in the mechanical and cold tests. Yokukansan significantly inhibited the cerebrospinal fluid dialysate level of glutamate that had increased by the stimulation of brush or acetone. Glutamate transporter inhibitors, DL-threo-beta-hydroxy aspartate and dihydrokainate, decreased the yokukansan-induced antiallodynic actions in CCI rats. Our results suggest that yokukansan was confirmed to have antiallodynic effects in CCI rats, which are related to a blockade of glutamatergic neurotransmission via activation of glutamate transporters in the spinal cord. Copyright © 2012 Yasuyuki Suzuki et al.


PubMed | Juntendo Tokyo Koto Geriatric Medical Center and Juntendo University
Type: | Journal: Modern rheumatology | Year: 2016

To determine mortality and its predictive factors in elderly Japanese patients with severe microscopic polyangiitis (MPA).This retrospective single-center study determined the mortality of 52 patients with MPA who were admitted to our geriatric medical center from 2002 to 2014. The variables at baseline, including patient demographics, clinical characteristics, and treatment, were analyzed for their association with mortality.Mean age at onset of MPA was 73.2 years, and the one-year survival rate was 65.9%. Relapse was observed in 32.7%. Among variables at diagnosis, age, cardiomyopathy, central nervous system (CNS) involvement, alveolar hemorrhage, disease severity, the 1996 Five-Factor Score (FFS), and the 2009 FFS were associated with mortality in univariate analysis. Cardiomyopathy, CNS involvement, age>65 years, disease severity, Birmingham Vasculitis Activity Score, the 1996 FFS, and the 2009 FFS were associated with relapse-free survival in univariate analysis.We investigated mortality and relapse-free survival and their predictive factors in elderly Japanese patients with severe MPA. Age, disease severity, the 1996 FFS, and the 2009 FFS at diagnosis were prognostic factors for both mortality and relapse-free survival.


Sekiya F.,Juntendo University | Yamaji K.,Juntendo University | Yang K.,Juntendo Tokyo Koto Geriatric Medical Center | Tsuda H.,Juntendo Tokyo Koto Geriatric Medical Center | Takasaki Y.,Juntendo University
Rheumatology International | Year: 2010

Osteonecrosis (ON) of the femoral head is known to occur commonly in cases with systemic lupus erythematosus (SLE) that received corticosteroid (CS) treatment. However, there have been no detailed reports about the onset of ON in cases with recurrence of SLE. Using MRI, we followed up 17 patients who experienced recurrence of SLE for at least 1 year at our hospital and in whom the CS dose was increased from a maintenance dose to middle to high dose to see if ON would occur. We then compared the group that developed ON and the group that did not with respect to patient characteristics, blood test results, changes in serum lipid levels, and CS dose. ON occurred in five subjects (29.4%), revealing that osteonecrosis occurs not only when CS are first administered but also in cases which the CS dose is increased for recurrence of SLE. Especially, serum cholesterol levels and its rate of increase soared rapidly soon after increasing the CS dose in the ON group as compared with the non-ON group (P < 0.05). This suggests that increased serum lipid levels might be a contributing factor to onset of ON. Moreover, SLE disease activity index 2000 (SLEDAI-2K) scores when the CS dose was increased were significantly (P < 0.05) higher in the ON group, suggesting that SLE disease activity itself is a risk factor for onset of ON. © 2009 Springer-Verlag.

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