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Daisuke Fukushi,1 Keigo Murakami,2 Yuji Watanabe,3 Norihiko Sugimoto,4 Hirotsugu Uehara,4 Masafumi Seki5 1Division of Gastroenterology, Tohoku Medical and Pharmaceutical University Hospital, Sendai City, Miyagi, Japan; 2Division of Pathology, Tohoku Medical and Pharmaceutical University Hospital, Sendai City, Miyagi, Japan; 3Laboratory for Clinical Microbiology, Tohoku Medical and Pharmaceutical University Hospital, Sendai City, Miyagi, Japan; 4Fuso Pharmaceutical Industry, Osaka City, Osaka, Japan; 5Division of Infectious Diseases and Infection Control, Tohoku Medical and Pharmaceutical University Hospital, Sendai City, Miyagi, JapanCorrespondence: Masafumi Seki, Division of Infectious Diseases and Infection Control, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai City, Miyagi, 983-8536, Japan, Tel +81-22-983-1221, Fax +81-22-290-8959, Email m-seki@tohoku-mpu.ac.jp; seki@hosp.tohoku-mpu.ac.jpBackground: Detection of Mycobacterium avium complex (MAC) in tissue is essential for the diagnosis of MAC infections when the Mycobacterium is not isolated from sputum. However, detection of MAC in paraffin-embedded sections has not been established.Methods: We encountered two patients with suspected MAC infections after surgery: patient 1 had a pulmonary nodule that was initially suspected to be lung cancer and was excised under video-assisted thoracoscopic surgery (VATS). Patient 2, who was under treatment with steroids and anti-IL-6 inhibitors for rheumatoid arthritis, was suspected to have disseminated ileocecal cancer with metastasis to the lung and skin. In both cases, we postoperatively detected MAC genes in paraffin-embedded tissue sections using the novel mycobacterial nucleic acid identification test, ie tissue-direct polymerase chain reaction (tdPCR)-based nucleic acid lateral flow immunoassay (NALFIA). Both patients showed granulomatous lesions with hematoxylin-eosin staining, and mycobacteria by Ziehl–Neelsen staining in tissue sections from the lung and skin, respectively, although MAC were not isolated from the sections. MAC genes were finally detected by tdPCR-NALFIA in both cases.Conclusion: Although Ziehl–Neelsen staining and culture tests are the gold standard in identifying causative mycobacteria, the rapid results of tdPCR-NALFIA performed simultaneously with sputum and/or tissue culture may make it an important auxiliary diagnostic tool for identifying mycobacterial infection, leading to improvement in the management of MAC patients.Keywords: Mycobacterium avium complex, MAC, Ziehl–Neelsen staining, rapid diagnosis

Kouichi Murakami,1 Emi Inayama,1 Yukiko Itoh,1 Shoji Tuchiya,1 Masashi Iwasaki,2 Nobuko Tamura,1 Toshihiko Suzuki,3 Noriko Iwai,1 Junji Utino,4 Motoyuki Masai,4 Daiji Nagayama,5,6 Kohji Shirai4,6 1Seijinaki Mihama Narita Clinic, Narita City, Chiba, 286-0041, Japan; 2Seijinkai Mihama Katori Clinic, Katori City, Chiba, 287-0041, Japan; 3Seijinkai Mihama Sakura Clinic, Sakura City, Chiba, 285-0841, Japan; 4Seijinkai Mihama Hospital, Chiba City, Chiba, 261-0013, Japan; 5Nagayama Clinic, Oyama City, Tochigi, 323-0032, Japan; 6Sakura Hospital, School of Medicine Toho University, Sakura City, Chiba, 285-8741, JapanCorrespondence: Daiji NagayamaNagayama Clinic, 2-12-22, Tenjin-Cho, Oyama City, Tochigi, 323-0032, JapanTel/Fax +81-285-22-0219Email deverlast96071@gmail.comAim: Mortality rate of maintenance hemodialysis patients is known to be high. Cardio-ankle vascular index (CAVI) is an index reflecting the proper stiffness of the arterial tree from the origin of the aorta to the ankle. We aimed to clarify the utility of CAVI as a predictor of mortality in hemodialysis patients. The roles of age and nutritional conditions on survival were also examined.Methods: We followed 242 patients undergoing hemodialysis for 6 consecutive years. Data from 209 patients (mean age was 60 ± 11 years) excluding those with ankle-brachial index < 0.90 were then analyzed. CAVI and heart to ankle pulse wave velocity (haPWV) were measured using Vasera 1500.Results: Thirty-eight hemodialysis patients who died during the 6-year period had higher age, cardiothoracic ratio (CTR), CAVI, and haPWV, and lower diastolic blood pressure, albumin, phosphate, and calcium phosphate product. The Kaplan–Meier curves for cumulative survival among the tertile groups showed that the mortality rate was higher in the highest tertile (T3) compared to T1/T2 for both CAVI and haPWV. Receiver operating characteristic (ROC) analysis revealed that CAVI had better discriminatory power for all-cause mortality compared to haPWV. In the Cox-proportional hazards analyses, 1 SD increase in both parameters contributed independently to all-cause mortality [CAVI: HR 1.595 (95% CI 1.108– 2.297), haPWV: HR 1.695 (95% CI 1.185– 2.425)], as well as age and CTR. Both parameters above the cut-offs estimated in the ROC analysis (CAVI ≥ 9.2, haPWV ≥ 8.9) also had independent contributions to mortality.Conclusion: Through the 6 consecutive years of follow-up in 209 HD patients, increased CAVI might represent a major modifiable risk factor for all-cause mortality. Further research is needed to examine whether CAVI-lowering interventions contribute to improved prognosis.Keywords: hemodialysis patient, mortality, cardio-ankle vascular index, phosphorus

Tempei Otsubo,1 Yoshinori Watanabe,2,3 Seiji Hongo,3 Mikichika Inoue,4 Kimiko Akimoto,4 Ken Murakami,5 Ryutaro Takahashi,6 Toshiaki Kikuchi7 1Department of Psychiatry, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan; 2Himorogi Psychiatric Institute, Tokyo, Japan; 3Nanko Clinic of Psychiatry, Shirakawa, Japan; 4Ikebukuro Internal Medicine, Tokyo, Japan; 5Murakami Hospital, Tokyo, Japan; 6Takahashi Clinic, Tokyo, Japan; 7Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan Aim: To assess the effectiveness and safety of switching the antidepressant formulation from immediate-release (IR) to controlled-release (CR) paroxetine in patients with major depressive disorder (MDD). Patients and methods: A total of 113 outpatients with MDD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and treated with a stable dose of IR paroxetine for at least 6 months were enrolled. Patients were then switched to CR paroxetine for 8 weeks. Effectiveness was evaluated by scores on the Himorogi Self-Rating Depression/Anxiety Scales (HSDS/HSAS) and the Clinical Global Impression – Severity (CGI-S). Safety was evaluated based on the reported adverse drug reactions (ADRs). Medication satisfaction and preference were assessed based on questionnaire responses using Likert-type scales. Results: The overall patient HSDS/HSAS scores significantly improved after switching from IR to CR paroxetine (P

This study proposes a method for evaluating shelter plan for emergency evacuation prior to a tsunami based on service area analysis. The evacuation service areas are generated using both spatial and network analysis based on Geographic Information System (GIS). A case study in Pacitan city, East Java Province, Indonesia which is located in the South coastal area of Java Island, is picked as study area. The field has a possibility of suffering tsunami disaster because of the movement of Indo-Australian plate and Eurasian plate. The simulation result shows that the current evacuation shelters arranged by local government are not easy to access if tsunami occurs. About 50% of the residents do not have enough time to evacuate to the shelters because many shelters are located far from residential area. Utilizing public buildings around residential area for temporary shelters proposed in this study, about 96% residents in inundation area have sufficient time to evacuate to the shelters.

Takahiro Terami,1 Jun Wada,1 Kentaro Inoue,1 Atsuko Nakatsuka,1,2 Daisuke Ogawa,1,2 Sanae Teshigawara,1 Kazutoshi Murakami,1,3 Akihiro Katayama,1 Jun Eguchi,1 Hirofumi Makino11Department of Medicine and Clinical Science, 2Department of Diabetic Nephropathy, 3Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanPurpose: Urinary angiotensinogen has been reported as a marker for the activation of intrarenal renin–angiotensin system (RAS) in various kidney diseases. To investigate the importance of urinary angiotensinogen in diabetic nephropathy, we compared the urinary levels of angiotensinogen, albumin, and α1-microglobulin.Materials and methods: Japanese patients with type 2 diabetes at various stages of nephropathy (n=85) were enrolled, and we measured albumin/creatinine ratio (ACR) and urinary excretion of angiotensinogen and α1-microglobulin. We also compared the clinical data of the patients treated with or without angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (RAS inhibitors [+], n=51; RAS inhibitors [−], n=34).Results: Urinary angiotensinogen levels positively correlated with ACR (r =0.367, P=3.84×10-4) and urinary α1-microglobulin (r=0.734, P=1.32 × 10-15), while they negatively correlated with estimated glomerular filtration ratio (eGFR) (r=−0.350, P=1.02 × 10-3) and high-density lipoprotein cholesterol (r=−0.216, P=0.049). Multiple regression analysis was carried out to predict urinary angiotensinogen levels by employing eGFR, ACR, and urinary α1-microglobulin as independent variables; only urinary α1-microglobulin entered the regression equation at a significant level. Although ACR was higher in the RAS inhibitors (+) group, urinary α1-microglobulin and angiotensinogen did not show significant increase in the RAS inhibitors (+) group.Conclusion: Urinary angiotensinogen is well correlated with urinary α1-microglobulin and reflected the tubular injuries which may be associated with the intrarenal RAS activation in patients with type 2 diabetes.Keywords: diabetic nephropathy, urinary biomarkers, renin–angiotensin system, angiotensinogen, α1-microglobulin, albumin

Pacharee Kantipong,1 Kuniko Murakami,2 Saiyud Moolphate,3 Myo Nyein Aung,4,5 Norio Yamada21Chiang Rai Prachanukroh Hospital, Thailand; 2Japan Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan; 3TB/HIV Research Project, Chiang Rai, Thailand; 4Department of Public Health, Graduate School of Medicine, Juntendo University, Tokyo, Japan; 5Department of Epidemiology, University of Public Health, Yangon, MyanmarBackground: The case fatality rate in patients with tuberculosis (TB) associated with human immunodeficiency virus (HIV) has been particularly high in Chiang Rai, Northern Thailand. It was almost 50% before the introduction of antiretroviral therapy in the last decade, and was still at 28% in 2008, despite expanding access to antiretroviral therapy. Reviewing the causes of death may lead to further understanding of the timeline and natural history of TB-HIV coinfection, and in so doing help to devise an effective prevention strategy in Chiang Rai. In this study, we aimed to investigate the distribution of confirmed causes of death in patients coinfected with TB and HIV in Chiang Rai, describe the causes of such deaths along the timeline of TB treatment, and identify predictors of each cause of death.Methods: In this retrospective study, we reviewed the causes of death for 331 patients who died of TB-HIV coinfection at Chiang Rai Prachanukroh Hospital from 2005 to 2008. Causes of death were confirmed by reviewing medical records, vital registration, and the TB register in the province, as well as obtaining reconfirmation by two experienced HIV physicians.Results: The confirmed causes of death were TB (39%), acquired immune deficiency syndrome (AIDS)-related opportunistic infections other than TB (AOI) (29%), and other systemic diseases which were neither TB nor AIDS-related opportunistic infections (nonTB-nonAOI) (16%). The definitive cause could not be confirmed in the remaining 16% of deaths. After starting the TB treatment, deaths caused by TB occurred earlier compared with deaths caused by AOI, which occurred steadily throughout the course of TB treatment, whilst deaths caused by non-TB-nonAOI increased gradually in later months. Further analysis by multivariate multinomial regression analysis showed that deaths in the first month (adjusted odds ratio [aOR] 4.64, 95% confidence interval [CI] 2.49–8.63), CD4 count ≥ 200 cells/mm3 (aOR 5.33, CI 1.05–26.10), non-category 1 TB treatment regimens (aOR 5.23, CI 1.04–9.77), and TB meningitis (aOR 3.27, CI 1.37–7.82) were significant predictors of confirmed TB deaths. Moreover, age over 45 years (aOR 3, CI 1.32–6.84) and admission as an inpatient were predictors of death caused by neither TB nor AIDS-related opportunistic infections (aOR 3.08, CI 1.39–6.80). Additional analysis showed that non-Thai patients (aOR 0.35, CI 0.12–0.99), those with an unknown CD4 count at TB diagnosis (aOR 0.16, CI 0.08–0.33), and those without an HIV diagnosis before TB treatment (aOR 0.32, CI 0.18–0.59) were less able to access antiretroviral therapy.Conclusion: The timeline and predictors of causes of death may assist in devising an intervention strategy for further reduction of the TB-HIV case fatality rate.Keywords: human immunodeficiency virus, tuberculosis, coinfection, cause of death, CD4, antiretroviral therapy

Pathogenic amyloid-β peptide precursor (APP) mutations clustered around position 693 of APP-position 22 of the Aβ sequence--are commonly associated with congophilic amyloid angiopathy (CAA) and intracerebral hemorrhages. In contrast, the Osaka (E693Δ) intra-Aβ APP mutation shows a recessive pattern of inheritance that leads to AD-like dementia despite low brain amyloid on in vivo positron emission tomography imaging. Here, we investigated the effects of the Osaka APP mutation on Aβ accumulation and deposition in vivo using a newly generated APP transgenic mouse model (E22ΔAβ) expressing the Osaka mutation together with the Swedish (K670N/M671L) double mutation. E22ΔAβ mice exhibited reduced α-processing of APP and early accumulation of intraneuronal fibrillar Aβ oligomers associated with cognitive deficits. In line with our in vitro findings that recombinant E22Δ-mutated Aβ peptides form amyloid fibrils, aged E22ΔAβ mice showed extracellular CAA deposits in leptomeningeal cerebellar and cortical vessels. In vitro results from thioflavin T aggregation assays with recombinant Aβ peptides revealed a yet unknown antiamyloidogenic property of the E693Δ mutation in the heterozygous state and an inhibitory effect of E22Δ Aβ42 on E22Δ Aβ40 fibrillogenesis. Moreover, E22Δ Aβ42 showed a unique aggregation kinetics lacking exponential fibril growth and poor seeding effects on wild-type Aβ aggregation. These results provide a possible explanation for the recessive trait of inheritance of the Osaka APP mutation and the apparent lack of amyloid deposition in E693Δ mutation carriers.