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Sample records for japanese patients clinically

  1. [Evidence from large clinical trials for Japanese hypertensive patients].

    PubMed

    Okura, Takafumi; Higaki, Jitsuo

    2011-11-01

    Large-scale clinical trials for the hypertensive patients have been carried out in Japan. Double-blind, placebo-controlled large clinical trials in Europe and USA showed that antihypertensive drugs prevented cardiovascular disease. Recently large clinical trials carried out in Japan. These clinical trials have shown that the onset rate of the heart vascular disease in Japanese hypertensive patients, the factor which influenced the onset of the cardiovascular disease, and the suppressant effect of cardiovascular disease of different antihypertensive drug class.

  2. Clinical characteristics of Japanese patients with severe hypertriglyceridemia.

    PubMed

    Tada, Hayato; Kawashiri, Masa-Aki; Nakahashi, Takuya; Yagi, Kunimasa; Chujo, Daisuke; Ohbatake, Azusa; Mori, Yukiko; Mori, Shunsuke; Kometani, Mitsuhiro; Fujii, Hiroshi; Nohara, Atsushi; Inazu, Akihiro; Mabuchi, Hiroshi; Yamagishi, Masakazu; Hayashi, Kenshi

    2015-01-01

    Although of interest, few data exist on the clinical characteristics of Japanese patients with an extremely high triglyceride level (≥ 1000 mg/dL). We assessed the clinical characteristics of Japanese patients with an extremely high triglyceride level. We investigated the presence of coronary artery disease, history of pancreatitis, the presence of fatty liver, and the potential causes of elevated triglyceride in Japanese subjects with an extremely high level of fasting triglyceride (≥ 1000 mg/dL) among 70,368 subjects whose serum triglyceride was measured for any reason at Kanazawa University Hospital from April 2004 to March 2014. We identified 215 (0.31%) subjects (mean age, 46 years; male, 170, mean body mass index, 25 kg/m(2)) with severe hypertriglyceridemia. Among them, 4 (1.9%) subjects were classified as type I, 97 (45.1%) subjects were type IV, and 114 (53.0%) subjects were type V hyperlipidemia, according to Fredrickson's classification. Among 215 subjects, 116 subjects (54.0%) drank alcohol, 58 (27.0%) showed heavy intake (≥ 60 g/d), and 64 (29.8%) subjects had diabetes. In total, 59 (27.4%) subjects had transient severe hypertriglyceridemia caused by corticosteroids (N = 19), antidepressant (N = 18), l-asparaginase and steroids for acute lymphoid leukemia (N = 15), hormone replacement therapy for breast cancer (N = 9), β-blocker (N = 5), hypothyroidism (N = 4), pregnancy (N = 4), and panhypopituitarism (N = 2). As many as 119 (55.3%) subjects exhibited fatty liver. Moreover, 12 (5.6%) and 17 (7.9%) subjects had a history of pancreatitis and coronary artery disease, respectively. A variety of situations can cause severe hypertriglyceridemia. We suggest that potential secondary causes should be carefully assessed for such patients. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  3. Clinical features of 405 Japanese patients with systemic sclerosis.

    PubMed

    Hashimoto, Atsushi; Endo, Hirahito; Kondo, Hirobumi; Hirohata, Shunsei

    2012-04-01

    We aimed to clarify the clinical features of Japanese patients with systemic sclerosis (SSc), especially with reference to organ involvement and autoantibodies. A cohort of 405 patients with SSc who attended our institution from 1973 to 2008 was identified retrospectively. Data on clinical features, including autoantibodies, organ involvement, and overlap of other connective tissue diseases, were obtained by following the medical records until 2009. The percentage of male patients during or after 1990 was greater than that before 1990 (3.9 vs. 10.6%, respectively). Limited cutaneous SSc (lSSc) was twice as frequent as diffuse cutaneous SSc (dSSc). About half of the patients had lung involvement (50.4%), while only 3.2% had scleroderma renal crisis. Male gender was associated with lung involvement, and dSSc was associated with most organ involvements except for pulmonary arterial hypertension (PAH). Anti-Scl-70 antibody was associated with lung or heart involvement, while anti-U1-RNP antibody was only associated with PAH. Conversely, patients with anti-centromere antibody had less organ involvement. SSc-Sjögren overlap syndrome was related to lSSc, further overlapping systemic lupus erythematosus (SLE), and less lung or heart involvement. In conclusion, these results not only confirmed previous reports but revealed several other findings, such as the increased proportion of male patients in recent years and the relationships between clinical features.

  4. [Clinical manifestations of ocular sarcoidosis in Japanese patients].

    PubMed

    Ohara, K

    1994-06-01

    Ocular sarcoidosis was found in 57.5 to 93.5% of Japanese patients with systemic sarcoidosis. Many studies reported a high female/male ratio with high percentage of patients at 20s and 50s in age in ocular sarcoidosis. A cardinal involvement was intraocular and manifested as uveitis. A combinations of granulomatous iritis, trabecular nodules, tent-like peripheral anterior synechia, snow-ball vitreous opacities, perivasculitis, and candle-wax or spotty chorioretinal exudates were characteristic and highly specific intraocular lesions. The lesions often lead ophthalmologists to systemic examinations. In suspects of ocular sarcoidosis who had no or sparse systemic findings, a diagnosis should remain tentative. Transbronchial lung biopsy showed non-caseating epithelioid granuloma in 37 of 60 patients with suspected ocular sarcoidosis who showed no bilateral hilar lymphadenopathy.

  5. Clinical characteristics of exudative age-related macular degeneration in Japanese patients.

    PubMed

    Maruko, Ichiro; Iida, Tomohiro; Saito, Masaaki; Nagayama, Dai; Saito, Kuniharu

    2007-07-01

    To clarify the clinical characteristics of exudative age-related macular degeneration (AMD) in Japanese patients. Retrospective, observational, consecutive case series. Two hundred and eighty-nine patients with neovascular AMD were examined. The authors classified the patients into three subtypes of neovascular AMD: polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and typical AMD. One hundred and fifty-eight patients (54.7%) were diagnosed with PCV and 102 patients (35.3%) with typical AMD. RAP was observed in 13 patients (4.5%). In 16 patients (5.5%), one eye had PCV and the other eye had typical AMD. Most patients with PCV and typical AMD had unilateral disease (81.6% and 94.1%, respectively) with a male preponderance (77.8% and 71.6%, respectively). Nine of 13 patients with RAP were female (69.2%). Patients with RAP were older (mean, 80.3 years for men and 75.3 years for women) than patients with other subtypes. Serous and hemorrhagic pigment epithelial detachment developed in 69 patients (43.7%) with PCV, 22 patients (21.6%) with typical AMD, and nine patients (69.2%) with RAP. In the patients with unilateral disease in each subtype, large drusen in the unaffected eye were seen in 24.0% with PCV, 30.2% with typical AMD, and 77.8% with RAP. Neovascular AMD in Japanese patients has different demographic features compared with that in White patients. In Japanese patients, there is a preponderance of PCV, male gender, unilaterality, and absence of drusen in the second eye, with the exception of RAP.

  6. Genotype-phenotype correlation in Japanese patients with familial Mediterranean fever: differences in genotype and clinical features between Japanese and Mediterranean populations.

    PubMed

    Kishida, Dai; Nakamura, Akinori; Yazaki, Masahide; Tsuchiya-Suzuki, Ayako; Matsuda, Masayuki; Ikeda, Shu-ichi

    2014-09-27

    Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent self-limiting fever and serositis that mainly affects Mediterranean populations. Many patients with FMF have been reported in Japan due to increasing recognition of this condition and the availability of genetic analysis for the gene responsible, MEFV. The present study was performed to elucidate the clinical characteristics of Japanese FMF patients and to examine the precise genotype-phenotype correlation in a large cohort of Japanese FMF patients. We analyzed the MEFV genotypes and clinical manifestations in 116 patients clinically diagnosed as having FMF and with at least one mutation. The most frequent mutation in Japanese patients was E148Q (40.2%), followed by M694I (21.0%), L110P (18.8%), P369S (5.4%), and R408Q (5.4%). In contrast, common mutations seen in Mediterranean patients, such as M694V, V726A, and M680I, were not detected in this population. The clinical features with M694I were associated with more severe clinical course compared to those seen with E148Q. P369S/R408Q showed variable phenotypes with regard to both clinical manifestations and severity. Patients with M694I showed a very favorable response to colchicine therapy, while those with P369S and R408Q did not. Clinical features and efficacy of treatment in Japanese FMF patients vary widely according to the specific MEFV gene mutation, and therefore genetic analysis should be performed for diagnosis in cases of Japanese FMF.

  7. Clinical implications of the coronary artery calcium score in Japanese patients.

    PubMed

    Yamamoto, Hideya; Kitagawa, Toshiro; Kihara, Yasuki

    2014-01-01

    Coronary artery calcification (CAC) is a well-established surrogate marker of the total burden of coronary atherosclerosis. The CAC score, as measured on coronary computed tomography (CT), is associated with the prevalence of coronary artery disease (CAD) as well as cardiovascular morbidity and mortality. The CAC score is used to reclassify coronary risks in asymptomatic individuals with intermediate risks. However, there are few clinical data regarding the usefulness of the CAC score for identifying high-risk Japanese patients. In this review article, we describe our previous studies of the prognostic value of the CAC score in patients with proven or suspected CAD. In addition, we reanalyzed our previous data for 723 patients with suspected CAD and found both all-cause and cardiovascular disease mortality to be significantly higher among the patients with a CAC score of ≥100 than among those with a CAC score of <100. Several studies from Japan have also shown that the CAC score is associated with the prevalence of obstructive CAD, as demonstrated on invasive coronary angiography or stress myocardial perfusion imaging. Furthermore, the CAC score provides useful information for performing coronary CT angiography, as asymptomatic patients without CAC are expected to have favorable outcomes. In contrast, the diagnostic accuracy is decreased in patients with a high CAC score (>400 or 600). In conclusion, the CAC score may have useful clinical applications in symptomatic and asymptomatic Japanese individuals. However, further studies are required to evaluate the prognostic value of this parameter for predicting cardiovascular morbidity and mortality in population-based analyses of asymptomatic Japanese subjects.

  8. [Clinical and pathophysiological features of Japanese patients with type 2 diabetes mellitus and their risk factors for diabetic complication].

    PubMed

    Sone, Hirohito

    2015-12-01

    The pathophysiological backgrounds as well as clinical phenotypes of Japanese or East Asian patients with type 2 diabetes are quite different from those in Western countries. According to results of East Asian large-scale studies such as the Japan Diabetes Complications Study (JDCS), which is a representative cohort of Japanese patients with type 2 diabetes, Japanese patients had a much lower body mass index and lower incidence of coronary heart disease compared with Caucasian diabetic patients. Other differences between Japanese and Caucasian patients with type 2 diabetes could be found in risk factors such as fruit intake on retinopathy and significance of triglycerides, or the effects of moderate alcohol drinking on cardiovascular disease. These results demonstrated a necessity of ethnic group-specific risk evaluations and care of type 2 diabetes and its complications.

  9. Temple syndrome: comprehensive molecular and clinical findings in 32 Japanese patients.

    PubMed

    Kagami, Masayo; Nagasaki, Keisuke; Kosaki, Rika; Horikawa, Reiko; Naiki, Yasuhiro; Saitoh, Shinji; Tajima, Toshihiro; Yorifuji, Tohru; Numakura, Chikahiko; Mizuno, Seiji; Nakamura, Akie; Matsubara, Keiko; Fukami, Maki; Ogata, Tsutomu

    2017-06-22

    PurposeTemple syndrome (TS14) is a rare imprinting disorder caused by aberrations at the 14q32.2 imprinted region. Here, we report comprehensive molecular and clinical findings in 32 Japanese patients with TS14.MethodsWe performed molecular studies for TS14 in 356 patients with variable phenotypes, and clinical studies in all TS14 patients, including 13 previously reported.ResultsWe identified 19 new patients with TS14, and the total of 32 patients was made up of 23 patients with maternal uniparental disomy (UPD(14)mat), six patients with epimutations, and three patients with microdeletions. Clinical studies revealed both Prader-Willi syndrome (PWS)-like marked hypotonia and Silver-Russell syndrome (SRS)-like phenotype in 50% of patients, PWS-like hypotonia alone in 20% of patients, SRS-like phenotype alone in 20% of patients, and nonsyndromic growth failure in the remaining 10% of patients in infancy, and gonadotropin-dependent precocious puberty in 76% of patients who were pubescent or older.ConclusionThese results suggest that TS14 is not only a genetically diagnosed entity but also a clinically recognizable disorder. Genetic testing for TS14 should be considered in patients with growth failure plus both PWS-like hypotonia and SRS-like phenotypes in infancy, and/or precocious puberty, as well as a familial history of Kagami-Ogata syndrome due to maternal microdeletion at 14q32.2.Genetics in Medicine advance online publication, 22 June 2017; doi:10.1038/gim.2017.53.

  10. Clinical characteristics of Japanese patients with axial spondyloarthritis, and short-term efficacy of adalimumab.

    PubMed

    Otsuka, Akiyo; Morita, Mitsuhiro; Yamada, Harumoto

    2015-11-01

    Ankylosing spondylitis (AS) is rarer in Japan than in Europe, probably because the European criteria, not well known by Japanese general physicians, regard AS as a progressive stage of axial spondyloarthritis (SpA). HLA-B27 is an important diagnostic marker of SpA; however, the incidence of the HLA-B27 allele is as low as 0.4 % in Japan. For Japanese SpA patients, other HLA alleles and clinical findings are required for earlier definitive diagnosis, for determining appropriate treatment timing, and for disease monitoring. We investigated the HLA-B alleles of 36 patients clinically diagnosed with SpA. For 8 axial SpA patients we evaluated the short-term efficacy of subcutaneous adalimumab injections (40 mg every other week for ≥11 months). Treatment efficacy was evaluated by use of the Bath Ankylosing Spondylitis Activity Index (BASDAI) score, and serum TNF-α and IL-6 levels were measured pre and post-treatment. Among the 36 Japanese SpA patients, the HLA-B27 allele occurred infrequently (5.6 %) whereas the HLA-B44 and 61 alleles were the most frequently detected (25.0 %). We also detected severe bamboo spine on radiography in the absence of the HLA-B27 allele. All 8 patients with axial SpA experienced significant symptom improvement after adalimumab treatment; the HLA-B27 allele was absent from these patients. Serum TNF-α and IL-6 levels were elevated in cases with remarkable inflammatory pain and high disease activity. These cytokines decreased after therapy, however. Most patients with normal cytokine levels at baseline retained these low levels. The findings reveal the short-term efficacy of adalimumab. The remarkably low incidence of HLA-B27 among our patients indicates that HLA-B distribution is different from that in other countries. Serum TNF-α and IL-6 levels were not effective as biomarkers for cases without high disease activity, and further research with larger samples is needed. The efficacy of TNF blockers, however, suggested a potential localized

  11. Clinical features and outcomes of 139 Japanese patients with Hodgkin lymphoma.

    PubMed

    Makita, Shinichi; Maruyama, Dai; Maeshima, Akiko Miyagi; Taniguchi, Hirokazu; Miyamoto, Ken-Ichi; Kitahara, Hideaki; Fukuhara, Suguru; Munakata, Wataru; Kobayashi, Yukio; Itami, Jun; Tobinai, Kensei

    2016-08-01

    Hodgkin lymphoma (HL) is a rare subtype of malignant lymphoma in Japan, and there are few reports of HL in Japan in recent years. We retrospectively analyzed the clinical features of 139 patients with HL who were diagnosed and treated at our institution between 1997 and 2011. The median age at diagnosis was 34 years with 83 male. Of these patients, 83 (60 %) were early stage and 56 (40 %) were advanced-stage. Seventy-three patients (88 %) with early stage disease received ABVd followed by irradiation. All of the 56 advanced-stage patients received chemotherapy, mainly ABVd. The 5-year progression-free survival (PFS) rates and overall survival rates were 90 and 94 % in patients with early stage disease, and 71 and 90 % in those with advanced-stage disease. The PFS of patients with advanced-stage disease was significantly lower than those with early stage (p = 0.014). In conclusion, the outcomes of Japanese patients with HL in recent years were not improved as compared with the results of previous reports. We confirmed that patients with advanced-stage disease have lower PFS than those with early stage disease. Prospective studies are needed to establish novel treatment strategies to improve the outcome of HL patients, especially those with advanced disease.

  12. Molecular and Clinical Studies in 138 Japanese Patients with Silver-Russell Syndrome

    PubMed Central

    Fuke, Tomoko; Mizuno, Seiji; Nagai, Toshiro; Hasegawa, Tomonobu; Horikawa, Reiko; Miyoshi, Yoko; Muroya, Koji; Kondoh, Tatsuro; Numakura, Chikahiko; Sato, Seiji; Nakabayashi, Kazuhiko; Tayama, Chiharu; Hata, Kenichiro; Sano, Shinichiro; Matsubara, Keiko; Kagami, Masayo; Yamazawa, Kazuki; Ogata, Tsutomu

    2013-01-01

    Background Recent studies have revealed relative frequency and characteristic phenotype of two major causative factors for Silver-Russell syndrome (SRS), i.e. epimutation of the H19-differentially methylated region (DMR) and uniparental maternal disomy 7 (upd(7)mat), as well as multilocus methylation abnormalities and positive correlation between methylation index and body and placental sizes in H19-DMR epimutation. Furthermore, rare genomic alterations have been found in a few of patients with idiopathic SRS. Here, we performed molecular and clinical findings in 138 Japanese SRS patients, and examined these matters. Methodology/Principal Findings We identified H19-DMR epimutation in cases 1–43 (group 1), upd(7)mat in cases 44–52 (group 2), and neither H19-DMR epimutation nor upd(7)mat in cases 53–138 (group 3). Multilocus analysis revealed hyper- or hypomethylated DMRs in 2.4% of examined DMRs in group 1; in particular, an extremely hypomethylated ARHI-DMR was identified in case 13. Oligonucleotide array comparative genomic hybridization identified a ∼3.86 Mb deletion at chromosome 17q24 in case 73. Epigenotype-phenotype analysis revealed that group 1 had more reduced birth length and weight, more preserved birth occipitofrontal circumference (OFC), more frequent body asymmetry and brachydactyly, and less frequent speech delay than group 2. The degree of placental hypoplasia was similar between the two groups. In group 1, the methylation index for the H19-DMR was positively correlated with birth length and weight, present height and weight, and placental weight, but with neither birth nor present OFC. Conclusions/Significance The results are grossly consistent with the previously reported data, although the frequency of epimutations is lower in the Japanese SRS patients than in the Western European SRS patients. Furthermore, the results provide useful information regarding placental hypoplasia in SRS, clinical phenotypes of the hypomethylated ARHI-DMR, and

  13. Molecular and clinical studies in 138 Japanese patients with Silver-Russell syndrome.

    PubMed

    Fuke, Tomoko; Mizuno, Seiji; Nagai, Toshiro; Hasegawa, Tomonobu; Horikawa, Reiko; Miyoshi, Yoko; Muroya, Koji; Kondoh, Tatsuro; Numakura, Chikahiko; Sato, Seiji; Nakabayashi, Kazuhiko; Tayama, Chiharu; Hata, Kenichiro; Sano, Shinichiro; Matsubara, Keiko; Kagami, Masayo; Yamazawa, Kazuki; Ogata, Tsutomu

    2013-01-01

    Recent studies have revealed relative frequency and characteristic phenotype of two major causative factors for Silver-Russell syndrome (SRS), i.e. epimutation of the H19-differentially methylated region (DMR) and uniparental maternal disomy 7 (upd(7)mat), as well as multilocus methylation abnormalities and positive correlation between methylation index and body and placental sizes in H19-DMR epimutation. Furthermore, rare genomic alterations have been found in a few of patients with idiopathic SRS. Here, we performed molecular and clinical findings in 138 Japanese SRS patients, and examined these matters. We identified H19-DMR epimutation in cases 1-43 (group 1), upd(7)mat in cases 44-52 (group 2), and neither H19-DMR epimutation nor upd(7)mat in cases 53-138 (group 3). Multilocus analysis revealed hyper- or hypomethylated DMRs in 2.4% of examined DMRs in group 1; in particular, an extremely hypomethylated ARHI-DMR was identified in case 13. Oligonucleotide array comparative genomic hybridization identified a ∼3.86 Mb deletion at chromosome 17q24 in case 73. Epigenotype-phenotype analysis revealed that group 1 had more reduced birth length and weight, more preserved birth occipitofrontal circumference (OFC), more frequent body asymmetry and brachydactyly, and less frequent speech delay than group 2. The degree of placental hypoplasia was similar between the two groups. In group 1, the methylation index for the H19-DMR was positively correlated with birth length and weight, present height and weight, and placental weight, but with neither birth nor present OFC. The results are grossly consistent with the previously reported data, although the frequency of epimutations is lower in the Japanese SRS patients than in the Western European SRS patients. Furthermore, the results provide useful information regarding placental hypoplasia in SRS, clinical phenotypes of the hypomethylated ARHI-DMR, and underlying causative factors for idiopathic SRS.

  14. Clinical characteristics of patients with gender identity disorder at a Japanese gender identity disorder clinic.

    PubMed

    Okabe, Nobuyuki; Sato, Toshiki; Matsumoto, Yosuke; Ido, Yumiko; Terada, Seishi; Kuroda, Shigetoshi

    2008-01-15

    The aim of this study was to examine the clinical characteristics of patients with gender identity disorder (GID) at a GID clinic in Japan. A total of 603 consecutive patients were evaluated at the GID clinic using clinical information and results of physical and neurological examinations. Using DSM-IV criteria, 579 patients (96.0%) were diagnosed with GID. Four patients were excluded for transvestic fetishism, eight for homosexuality, five for schizophrenia, three for personality disorders, and four for other psychiatric disorders. Among the GID patients, 349 (60.3%) were the female-to-male (FTM) type, and 230 (39.7%) were the male-to-female (MTF) type. Almost all FTM-type GID patients started to feel discomfort with their sex before puberty and were sexually attracted to females. The proportion of FTM patients who had experienced marriage as a female was very low, and very few had children. Therefore, FTM-type GID patients seem to be highly homogeneous. On the other hand, various patterns of age at onset and sexual attraction existed among MTF patients. Among the MTF-type GID patients, 28.3% had married as males and 18.7% had sired children. Thus, MTF-type GID patients seem to be more heterogeneous.

  15. Bortezomib therapy-related lung disease in Japanese patients with multiple myeloma: incidence, mortality and clinical characterization.

    PubMed

    Yoshizawa, Kazutake; Mukai, Harumi Y; Miyazawa, Michiko; Miyao, Makiko; Ogawa, Yoshimasa; Ohyashiki, Kazuma; Katoh, Takao; Kusumoto, Masahiko; Gemma, Akihiko; Sakai, Fumikazu; Sugiyama, Yukihiko; Hatake, Kiyohiko; Fukuda, Yuh; Kudoh, Shoji

    2014-02-01

    Because of the potentially high mortality rate (6.5%) associated with bortezomib-induced lung disease (BILD) in Japanese patients with relapsed or refractory multiple myeloma, we evaluated the incidence, mortality and clinical features of BILD in a Japanese population. This study was conducted under the Risk Minimization Action Plan (RMAP), which was collaboratively developed by the pharmaceutical industry and public health authority. The RMAP consisted of an intensive dissemination of risk information and a recommended countermeasure to health-care professionals. All patients treated with bortezomib were consecutively registered in the study within 1 year and monitored for emerging BILD. Of the 1010 patients registered, 45 (4.5%) developed BILD, 5 (0.50%) of whom had fatal cases. The median time to BILD onset from the first bortezomib dose was 14.5 days, and most of the patients responded well to corticosteroid therapy. A retrospective review by the Lung Injury Medical Expert Panel revealed that the types with capillary leak syndrome and hypoxia without infiltrative shadows were uniquely and frequently observed in patients with BILD compared with those with conditions associated with other molecular-targeted anticancer drugs. The incidence rate of BILD in Japan remains high compared with that reported in other countries, but the incidence and mortality rates are lower than expected before the introduction of bortezomib in Japan. This study describes the radiographic pattern and clinical characterization of BILD in the Japanese population. The RMAP seemed clinically effective in minimizing the BILD risk among our Japanese population. © 2013 Janssen Pharmaceutical K.K. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  16. Clinical and Genetic Characteristics of Japanese Patients with Age-Related Macular Degeneration and Pseudodrusen.

    PubMed

    Elfandi, Sufian; Ooto, Sotaro; Ueda-Arakawa, Naoko; Takahashi, Ayako; Yoshikawa, Munemitsu; Nakanishi, Hideo; Tamura, Hiroshi; Oishi, Akio; Yamashiro, Kenji; Yoshimura, Nagahisa

    2016-10-01

    To investigate differences in clinical characteristics and genotype distribution in Japanese patients with age-related macular degeneration (AMD) and pseudodrusen using multimodal imaging. Retrospective, observational case series. A total of 101 patients (101 eyes) with AMD and pseudodrusen. Patients underwent complete ophthalmologic examination, including color fundus photography, infrared reflectance (IR) imaging, fundus autofluorescence, confocal blue reflectance, fluorescein and indocyanine green (ICG) angiography, and spectral-domain optical coherence tomography (SD OCT). Pseudodrusen subtype was identified with multiple imaging techniques. Patients were genotyped to identify major single nucleotide polymorphisms associated with AMD (CFH Y402, CFH I62V, and ARMS2 A69S). Clinical characteristics and genetic distributions of patients with pseudodrusen. At least 1 imaging technique identified dot pseudodrusen in all 101 eyes and ribbon pseudodrusen in 53 eyes (52.5%). Forty-eight eyes (47.5%) had only dot pseudodrusen, but no eyes had only ribbon pseudodrusen or midperipheral drusen. Forty-five of 49 bilateral cases (91.8%) had the same pseudodrusen subtype in both eyes. Pseudodrusen subtype did not change during the observation period in 100 eyes (99.0%), but dot-dominant type changed to dot-ribbon type in 1 eye (1.0%). The dot and ribbon subtypes were detected in 84 (83.1%) and 51 (96.2%) eyes, respectively, using color fundus photographs. Detection sensitivity of dot pseudodrusen was high for IR (97.0%), confocal blue reflectance (95.1%), fundus autofluorescence (93.1%), and ICG (100%) imaging. Detection sensitivity for ribbon pseudodrusen was high for color fundus photography (96.2%), confocal blue reflectance (94.3%), and fundus autofluorescence (90.6%), but not for IR imaging and ICG angiography. Risk allele frequency of the CFH I62V polymorphism was 79.8% and 67.0% in patients with dot-dominant and dot-ribbon pseudodrusen, respectively (P = 0.053). The

  17. Pharmacokinetics, efficacy and safety profiles of etanercept monotherapy in Japanese patients with rheumatoid arthritis: review of seven clinical trials

    PubMed Central

    Miyasaka, Nobuyuki; Kawai, Shinichi; Yuasa, Hirotoshi; Yamashita, Noriaki; Sugiyama, Noriko; Wagerle, Lorin Craig; Vlahos, Bonnie; Wajdula, Joseph

    2015-01-01

    Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The aim of this review was to summarize the clinical program for ETN monotherapy in Japanese patients with RA, which has included a pharmacokinetic study, clinical trials for registration, long-term studies, and once-weekly dosing studies. Pharmacokinetic results showed that serum concentrations of ETN were linear with dose levels and were similar to other international studies. Across interventional studies, 652 Japanese patients with active RA were treated with ETN. In the registration studies, ETN treatment led to consistent improvement in American College of Rheumatology 20/50/70 scores, European League Against Rheumatism Good Response, Disease Activity Score 28 erythrocyte sedimentation rate remission, and Health Assessment Questionnaire disability index. In the long-term studies, efficacy was maintained for up to 180 weeks. Similar results were seen in the once-weekly studies. Across the studies, more than 870 patient-years of exposure to ETN were recorded. Discontinuations owing to lack of efficacy or adverse events were modest and no new safety signals were recorded. These studies demonstrated that ETN monotherapy is efficacious and well-tolerated in Japanese patients with RA. PMID:24842477

  18. Bortezomib therapy-related lung disease in Japanese patients with multiple myeloma: Incidence, mortality and clinical characterization

    PubMed Central

    Yoshizawa, Kazutake; Mukai, Harumi Y; Miyazawa, Michiko; Miyao, Makiko; Ogawa, Yoshimasa; Ohyashiki, Kazuma; Katoh, Takao; Kusumoto, Masahiko; Gemma, Akihiko; Sakai, Fumikazu; Sugiyama, Yukihiko; Hatake, Kiyohiko; Fukuda, Yuh; Kudoh, Shoji

    2014-01-01

    Because of the potentially high mortality rate (6.5%) associated with bortezomib-induced lung disease (BILD) in Japanese patients with relapsed or refractory multiple myeloma, we evaluated the incidence, mortality and clinical features of BILD in a Japanese population. This study was conducted under the Risk Minimization Action Plan (RMAP), which was collaboratively developed by the pharmaceutical industry and public health authority. The RMAP consisted of an intensive dissemination of risk information and a recommended countermeasure to health-care professionals. All patients treated with bortezomib were consecutively registered in the study within 1 year and monitored for emerging BILD. Of the 1010 patients registered, 45 (4.5%) developed BILD, 5 (0.50%) of whom had fatal cases. The median time to BILD onset from the first bortezomib dose was 14.5 days, and most of the patients responded well to corticosteroid therapy. A retrospective review by the Lung Injury Medical Expert Panel revealed that the types with capillary leak syndrome and hypoxia without infiltrative shadows were uniquely and frequently observed in patients with BILD compared with those with conditions associated with other molecular-targeted anticancer drugs. The incidence rate of BILD in Japan remains high compared with that reported in other countries, but the incidence and mortality rates are lower than expected before the introduction of bortezomib in Japan. This study describes the radiographic pattern and clinical characterization of BILD in the Japanese population. The RMAP seemed clinically effective in minimizing the BILD risk among our Japanese population. PMID:24329927

  19. Clinical and immunological studies for 105 Japanese seropositive patients of epidermolysis bullosa acquisita examined at Kurume University.

    PubMed

    Hashimoto, Takashi; Jin, Zhexiong; Ishii, Norito

    2016-08-01

    Using our serological diagnostic criteria, we selected 105 Japanese patients with epidermolysis bullosa acquisita (EBA), an autoimmune bullous disease (AIBD) reacting with type VII collagen, from our cohort of 5063 AIBD patients. We examined the patients clinically and immunologically. We found diversity of clinical manifestations in both cutaneous and oral mucosal lesions and a high rate of inflammatory-type EBA patients in Japan. Common treatments were systemic steroids, followed by immunosuppressives, DDS, tetracycline/minocycline and colchicine. Immunological studies revealed that indirect immunofluorescence of 1M-NaCl-split skin, immunoblotting of dermal extract, and type VII collagen ELISA were sensitive methods, with possible multiplicity of circulating autoantibodies against other basement membrane autoantigens. The present study analyzed the largest cohort of EBA patients, confirming the scarcity of EBA (only 105 of the 5063 AIBD patients), and showed that the three serological tests are useful for the diagnosis of EBA.

  20. Montelukast in the treatment of perennial allergic rhinitis in paediatric Japanese patients; an open-label clinical trial

    PubMed Central

    Okubo, Kimihiro; Inoue, Yoichi; Numaguchi, Hirotaka; Tanaka, Kumi; Saito, Itori; Oshima, Nobuyuki; Matsumoto, Yuki; Prohn, Marita; Mehta, Anish; Nishida, Chisato; Philip, George

    2016-01-01

    Abstract Background: This study was conducted to evaluate the safety and tolerability, and population pharmacokinetics (PPK) of montelukast as well as efficacy in the treatment of perennial allergic rhinitis (PAR) in paediatric Japanese patients aged between 1 and 15 years. Methods: In this multi-centre, open-label trial, 87 paediatric Japanese patients with PAR received montelukast 4 mg oral granules (OG) for 4 weeks (1–5-year-olds, N = 15), 4 mg OG for 12 weeks (1–5-year-olds, N = 36), 5 mg chewable tablets (CT) for 12 weeks (6–9-year-olds, N = 18), or 5 mg CT for12 weeks (10–15-year-olds, N = 18). Clinical exams and laboratory assessments were conducted at study visits, and adverse events (AE) were monitored throughout the study up to 14 days after the last visit. Population pharmacokinetic approach was used to estimate AUC0–∞, Cmax, Tmax and apparent elimination half-life in each age group. Efficacy was assessed based on global evaluations by the subject’s caregiver. Results: There were no serious AEs and one discontinuation due to an AE. The most common AEs in any of the treatment groups were nasopharyngitis, pharyngitis, and acute sinusitis. Montelukast exposure (AUC0–∞) was similar in the 1–5-year-old group and the 6–9-year-old group, but 19% lower in the 10–15-year-old group. Among all patients, the total proportion of patients whose global evaluation was “very much better” was 5.7% (week 2), 11.5% (week 4), and 16.9% (week 12) reflecting improvement in symptoms over time. Conclusion: Montelukast was generally well tolerated in Japanese children with PAR. AUC0–∞was similar in 1–5 and 6–9-year-olds, while a lower exposure was observed in the 10–15-year-old group likely due to differences in bodyweight. The exposure in Japanese paediatric patients was generally consistent with that in non-Japanese paediatric and adult patients. As assessed by the patients’ caregivers, montelukast also

  1. Effects of HLA-DRB1 alleles on susceptibility and clinical manifestations in Japanese patients with adult onset Still's disease.

    PubMed

    Asano, Tomoyuki; Furukawa, Hiroshi; Sato, Shuzo; Yashiro, Makiko; Kobayashi, Hiroko; Watanabe, Hiroshi; Suzuki, Eiji; Ito, Tomoyuki; Ubara, Yoshifumi; Kobayashi, Daisuke; Iwanaga, Nozomi; Izumi, Yasumori; Fujikawa, Keita; Yamasaki, Satoshi; Nakamura, Tadashi; Koga, Tomohiro; Shimizu, Toshimasa; Umeda, Masataka; Nonaka, Fumiaki; Yasunami, Michio; Ueki, Yukitaka; Eguchi, Katsumi; Tsuchiya, Naoyuki; Tohma, Shigeto; Yoshiura, Koh-Ichiro; Ohira, Hiromasa; Kawakami, Atsushi; Migita, Kiyoshi

    2017-09-12

    HLA-DRB1 alleles are major determinants of genetic predisposition to rheumatic diseases. We assessed whether DRB1 alleles are associated with susceptibility to particular clinical features of adult onset Still's disease (AOSD) in a Japanese population by determining the DRB1 allele distributions. DRB1 genotyping of 96 patients with AOSD and 1,026 healthy controls was performed. Genomic DNA samples from the AOSD patients were also genotyped for MEFV exons 1, 2, 3, and 10 by direct sequencing. In Japanese patients with AOSD, we observed a predisposing association of DRB1*15:01 (p = 8.60 × 10(-6), corrected p (Pc) = 0.0002, odds ratio (OR) = 3.04, 95% confidence interval (95% CI) = 1.91-4.84) and DR5 serological group (p = 0.0006, OR = 2.39, 95% CI = 1.49-3.83) and a protective association of DRB1*09:01 (p = 0.0004, Pc = 0.0110, OR = 0.34, 95% CI = 0.18-0.66) with AOSD, and amino acid residues 86 and 98 of the DRβ chain were protectively associated with AOSD. MEFV variants were identified in 49 patients with AOSD (56.3%). The predisposing effect of DR5 was confirmed only in patients with AOSD who had MEFV variants and not in those without MEFV variants. Additionally, DR5 in patients with AOSD are associated with macrophage activation syndrome (MAS) and steroid pulse therapy. The DRB1*15:01 and DR5 are both associated with AOSD susceptibility in Japanese subjects. A protective association between the DRB1*09:01 allele and AOSD was also observed in these patients. Our data also highlight the effects of DRB1 alleles in susceptibility to AOSD.

  2. [Gender difference of clinical features in Japanese patients with alcoholic liver cirrhosis].

    PubMed

    Kawashima, Osamu; Ohata, Mitsuru; Sakamoto, Kazuhiko; Hashimoto, Kenichi; Nakajima, Hisato; Yamauchi, Masayoshi

    2003-02-01

    Gender difference of alcohol intake and laboratory data was investigated in 165 Japanese patients with alcoholic liver cirrhosis. Mean age of first drinking and habitual drinking were higher in female. Duration of drinking was shorter in female. Although cumulative alcohol intake was larger in male, mean daily alcohol intake did not differ in both gender. Moreover, daily alcohol intake adjusted to body weight was significantly larger in female. Body mass index, serum levels of total protein, albumin and cholinesterase were significantly decreased in female. Platelet counts on admission did not differ in both gender. However, it was significantly increased in female after one month abstinence. C reactive protein, ammonia and serum levels of total bilirubin were significantly higher in female as compared to male. In conclusion, female alcoholics seems to progress to liver cirrhosis earlier because of high daily alcohol intake adjusted to body weight, poor nutritional condition and inflammation caused by endotoxin.

  3. Mutation Profile of B-Raf Gene Analyzed by fully Automated System and Clinical Features in Japanese Melanoma Patients.

    PubMed

    Ide, Masaru; Koba, Shinichi; Sueoka-Aragane, Naoko; Sato, Akemi; Nagano, Yuri; Inoue, Takuya; Misago, Noriyuki; Narisawa, Yutaka; Kimura, Shinya; Sueoka, Eisaburo

    2017-01-01

    BRAF gene mutations have been observed in 30-50 % of malignant melanoma patients. Recent development of therapeutic intervention using BRAF inhibitors requires an accurate and rapid detection system for BRAF mutations. In addition, the clinical characteristics of the melanoma associated with BRAF mutations in Japanese patients have not been investigated on a large scale evaluation. We recently established quenching probe system (QP) for detection of an activating BRAF mutation, V600E and evaluated 113 melanoma samples diagnosed in Saga University Hospital from 1982 to 2011. The QP system includes fully automated genotyping, based on analysis of the probe DNA melting curve, which binds the target mutated site using a fluorescent guanine quenched probe. BRAF mutations were detected in 54 of 115 (47 %) including 51 of V600E and 3 of V600 K in Japanese melanoma cases. Among clinical subtypes of melanoma, nodular melanoma showed high frequency (12 of 15; 80 %) of mutation followed by superficial spreading melanoma (13 of 26; 50 %). The QP system is a simple and sensitive method to determine BRAF V600E mutation, and will be useful tool for patient-oriented therapy with BRAF inhibitors.

  4. Virtual patients to explore and develop clinical case summary statement skills amongst Japanese resident physicians: a mixed methods study.

    PubMed

    Heist, Brian S; Kishida, Naoki; Deshpande, Gautam; Hamaguchi, Sugihiro; Kobayashi, Hiroyuki

    2016-02-01

    In Western clinical training, formulation of a summary statement (SS) is a core exercise for articulation, evaluation, and improvement of clinical reasoning (CR). In Japanese clinical training, structured guidance in developing CR, including opportunity for SS practice, is uncommon, and the present status of case summarization skills is unclear. We used Virtual Patients (VPs) to explore Japanese junior residents' SS styles and the effectiveness of VPs on improving SS quality. All first-year junior resident physicians at 4 residency programs (n = 54) were assigned randomized sequences of 5 VP modules, rolled out at 6 day intervals. During each module, participants free-texted a case summary and then reviewed a model summary. Thematic analysis was used to identify SS styles and each SS was categorized accordingly. Frequency of SS styles, and SS CR quality determined by 1) an internally developed Key Feature rubric and 2) demonstration of semantic qualification, were compared across modules. Four SS styles were identified: numbered features matched to differential diagnoses, differential diagnoses with supportive comments, feature listing, and narrative summarization. From module #1 to #5, significant increases in the narrative summarization SS style (p = 0.016), SS CR quality score (p = 0.021) and percentage of semantically driven SS (p = 0.003) were observed. Our study of Japanese junior residents identified distinct clinical case summary statement styles, and observed adoption of the narrative summarization style and improvement in the CR quality of summary statements during a series of VP cases.

  5. A Spectrum of Clinical Presentations in Seven Japanese Patients with Vitamin D Deficiency

    PubMed Central

    Kubota, Takuo; Kotani, Tomoo; Miyoshi, Yoko; Santo, Yoko; Hirai, Haruhiko; Namba, Noriyuki; Shima, Masaaki; Shimizu, Kazuo; Nakajima, Shigeo; Ozono, Keiichi

    2006-01-01

    Recently, the reemergence of vitamin D deficiency in developed countries has been pointed out. Vitamin D deficiency is diagnosed based on the serum 25-hydroxyvitamin D (25OHD) level. However, its normal range is still controversial, making the diagnosis of vitamin D deficiency difficult. Here, we present seven Japanese patients diagnosed with vitamin D deficiency. Three patients complained of leg bowing, and the other four of tetany. The patients with leg bowing were toddlers. Radiographic surveys demonstrated evidence of rickets. Laboratory findings showed decreased levels of serum inorganic phosphorus and increased levels of alkaline phosphatase (ALP) and intact-parathyroid hormone (iPTH). The serum levels of 25OHD were relatively low, ranging from 13 to 15.2 ng/ml. Of the patients with tetany, three were young infants. Laboratory findings showed decreased levels of serum calcium and increased levels of ALP and iPTH. The serum levels of 25OHD were markedly decreased (below 8 ng/ml). Thus, these results indicate that relatively low levels of 25OHD can cause rickets, a symptom of vitamin D deficiency, and that clinicians should therefore carefully evaluate the levels of 25OHD. PMID:24790316

  6. Safety and efficacy of sorafenib in Japanese patients with hepatocellular carcinoma in clinical practice: a subgroup analysis of GIDEON.

    PubMed

    Kudo, Masatoshi; Ikeda, Masafumi; Takayama, Tadatoshi; Numata, Kazushi; Izumi, Namiki; Furuse, Junji; Okusaka, Takuji; Kadoya, Masumi; Yamashita, Satoshi; Ito, Yuichiro; Kokudo, Norihiro

    2016-12-01

    GIDEON was a prospective, global, non-interventional study evaluating the safety of sorafenib in patients with unresectable hepatocellular carcinoma in real-world practice. The aim of this subgroup analysis was to assess the safety and efficacy of sorafenib as used by Japanese patients. In Japan, 508 patients were valid for safety analysis. Efficacy and safety were evaluated by the Child-Pugh score. The number of patients with Child-Pugh A and B was 432 (85.0 %) and 58 (11.4 %), respectively. The median overall survival time and time to progression in patients with Child-Pugh A and Child-Pugh B were 17.4 and 4.9 months, 3.7 and 2.3 months, respectively. The most common drug-related adverse events (AEs) included hand-foot skin reaction (47.8 %), diarrhea (35.8 %) and hypertension (24.2 %). The incidences of all or drug-related AEs were similar between patients with Child-Pugh A and B. However, all or drug-related serious AEs, AEs resulting in permanent discontinuation of sorafenib and deaths were observed more frequently in patients with Child-Pugh B compared with Child-Pugh A. Duration of treatment tended to be shorter as the Child-Pugh score worsened. Sorafenib was well tolerated by Japanese HCC patients in clinical settings. Patients with Child-Pugh B had shorter duration of treatment and higher incidence of SAEs. It is important to carefully evaluate patients' conditions and assess the benefit and risk before making a decision to treat patients with sorafenib.

  7. Clinical Implication of Plasma Hydrogen Sulfide Levels in Japanese Patients with Type 2 Diabetes

    PubMed Central

    Suzuki, Kunihiro; Sagara, Masaaki; Aoki, Chie; Tanaka, Seiichi; Aso, Yoshimasa

    2017-01-01

    Objective The goal of the present study was to investigate the plasma hydrogen sulfide (H2S) levels in patients with type 2 diabetes, as the plasma H2S levels in Japanese patients with type 2 diabetes remain unclear. Methods The plasma H2S levels were measured in 154 outpatients with type 2 diabetes and 66 outpatients without diabetes. All blood samples were collected in the outpatient department from 09:00 to 10:00. The patients had fasted from 21:00 the previous evening and had not consumed alcohol or caffeine or smoked until sample collection. The plasma H2S levels were measured using the methylene blue assay. The plasma H2S levels were determined in triplicate, and the average concentrations were calculated against a calibration curve of sodium sulfide. Results The patients with type 2 diabetes showed a progressive reduction in the plasma H2S levels (45.1±15.5 μM versus 54.0±26.4 μM, p<0.05), which paralleled poor glycemic control. There was a significant correlation between a reduction in the plasma H2S levels and the HbA1c levels (β=-0.505, p<0.01), Furthermore, a reduction in the plasma H2S levels was found to be related to a history of cardiovascular diseases in patients with type 2 diabetes (39.9±13.8 μM versus 47.5±15.9 μM, p<0.01). Conclusion Collectively, the plasma H2S levels were reduced in patients with type 2 diabetes, which may have implications in the pathophysiology of cardiovascular disease in diabetic patients. The trial was registered with the University Hospital Medical Information Network (UMIN no. #000020549). PMID:28049995

  8. Differences in the clinical course of 516 Japanese patients with upper gastrointestinal bleeding between weekday and weekend admissions.

    PubMed

    Fujita, Minoru; Manabe, Noriaki; Murao, Takahisa; Osawa, Motoyasu; Hirai, Shinsuke; Fukushima, Shinya; Shogen, Yo; Nakato, Rui; Ishii, Manabu; Matsumoto, Hiroshi; Hata, Jiro; Shiotani, Akiko

    2017-09-19

    Patients suspected of having upper gastrointestinal bleeding (UGIB) admitted during the weekend tend to have a poor outcome in western countries. However, no Japanese studies have been reported on this matter. We aimed to evaluate differences in the clinical course of patients with UGIB between weekday and weekend admissions in Japan. Medical records of patients who had undergone emergency endoscopy for UGIB were retrospectively reviewed. The severity of UGIB was evaluated using the Glasgow-Blatchford (GB) and AIMS65 score. Patients in whom UGIB was stopped and showed improved iron deficiency anemia after admission were considered as having a good clinical course. We reviewed 516 consecutive patients and divided them into two groups: Group A (daytime admission on a weekday: 234 patients) and Group B (nighttime or weekend admission: 282 patients). There was no significant difference in GB and AIM65 scores between the Groups. The proportions of patients with good clinical course were not significantly different between groups (A, 67.5% and B, 67.0%; p = .90). However, patients in Group B underwent hemostatic treatments more frequently compared with those in Group A (58.5% vs 47.4%, p = .012). Multivariate analysis showed that taking acid suppressants, no need for blood transfusions, use of hemostatic treatments, and GB score <12 were associated with a good clinical course. There were no significant differences in the clinical outcomes of patients with UGIB admitted during daytime on weekdays and those admitted at nighttime or weekends partly owing to the sufficient performance of endoscopic hemostatic treatments.

  9. Evaluation of factors affecting continuous performance test identical pairs version score of schizophrenic patients in a Japanese clinical sample.

    PubMed

    Koide, Takayoshi; Aleksic, Branko; Kikuchi, Tsutomu; Banno, Masahiro; Kohmura, Kunihiro; Adachi, Yasunori; Kawano, Naoko; Iidaka, Tetsuya; Ozaki, Norio

    2012-01-01

    Aim. Cognitive impairment in schizophrenia strongly relates to social outcome and is a good candidate for endophenotypes. When we accurately measure drug efficacy or effects of genes or variants relevant to schizophrenia on cognitive impairment, clinical factors that can affect scores on cognitive tests, such as age and severity of symptoms, should be considered. To elucidate the effect of clinical factors, we conducted multiple regression analysis using scores of the Continuous Performance Test Identical Pairs Version (CPT-IP), which is often used to measure attention/vigilance in schizophrenia. Methods. We conducted the CPT-IP (4-4 digit) and examined clinical information (sex, age, education years, onset age, duration of illness, chlorpromazine-equivalent dose, and Positive and Negative Symptom Scale (PANSS) scores) in 126 schizophrenia patients in Japanese population. Multiple regression analysis was used to evaluate the effect of clinical factors. Results. Age, chlorpromazine-equivalent dose, and PANSS-negative symptom score were associated with mean d' score in patients. These three clinical factors explained about 28% of the variance in mean d' score. Conclusions. As conclusion, CPT-IP score in schizophrenia patients is influenced by age, chlorpromazine-equivalent dose and PANSS negative symptom score.

  10. Demographic and clinical features of autoimmune thyroid disorder in Japanese patients with systemic sclerosis.

    PubMed

    Toki, Sayaka; Motegi, Sei-ichiro; Yamada, Kazuya; Uchiyama, Akihiko; Ishikawa, Osamu

    2014-12-01

    Autoimmune thyroid disorders (AITD) are characterized by the impairment of the thyroid gland as a result of systemic or organ-specific autoimmune disorders, and the presence of antithyroid autoantibodies, such as antithyroglobulin antibody (AbTg) and antithyroid peroxidase antibody (AbTPO). Several studies have reported the association of AITD with systemic sclerosis (SSc). However, none of those studies analyzed the association between AITD and skin sclerosis in SSc patients. The aim of this study was to examine the demographic and clinical features of SSc patients with AITD treated in our department. Of a total of 210 SSc patients, we identified 30 with AITD (14.3%), including 29 with Hashimoto's disease (13.8%) and one patient with Graves' disease (0.5%), indicating that hypothyroidism was more common among SSc patients with AITD. All patients with AITD were female, and anticentromere antibody positivity, the complication of Sjögren's syndrome, severe facial skin sclerosis and atrophy of the thyroid gland were significantly prevalent in SSc patients with AITD. SSc patients with such clinical features may be at high risk of AITD and require regular follow up of thyroid function including ultrasonography and the examination of serum hormone levels to start an early treatment.

  11. Incidence of dizziness and vertigo in Japanese primary care clinic patients with lifestyle-related diseases: an observational study

    PubMed Central

    Wada, Masaoki; Takeshima, Taro; Nakamura, Yosikazu; Nagasaka, Shoichiro; Kamesaki, Toyomi; Oki, Hiroshi; Kajii, Eiji

    2015-01-01

    Objective Dizziness and vertigo are highly prevalent symptoms among patients presenting at primary care clinics, and peripheral vestibular disorder (PVD) is their most frequent cause. However, the incidence of PVD has not been well documented. This study aimed to investigate the incidence of dizziness, vertigo, and PVD among patients presenting at a primary care clinic. Design This was an observational study. Setting and participants Between November 2011 and March 2013, we observed 393 patients, all at least 20 years old, who had been treated for chronic diseases such as hypertension, dyslipidemia, and diabetes mellitus for at least 6 months at a primary clinic (Oki Clinic) in Japan. Outcome The main outcome of interest was new incidence of dizziness, vertigo, and PVD events. During the 1-year follow-up period, the otorhinolaryngologist diagnosed and reported new PVD events. Results The mean age of the 393 participants at entry was 65.5 years. Of the study participants, 12.7%, 82.4%, and 92.6% had diabetes mellitus, hypertension, and dyslipidemia, respectively. We followed up all the participants (100%). During the 662.5 person-years of follow-up, 121 cases of dizziness or vertigo (dizziness/vertigo) and 76 cases of PVD were observed. The incidence of dizziness/vertigo and PVD was 194.7 (95% confidence interval: 161.6–232.6) per 1,000 person-years and 115.7 (95% confidence interval: 92.2–142.6) per 1,000 person-years, respectively. There were 61 cases of acute peripheral vestibulopathy, 12 of benign paroxysmal positional vertigo, and three of Meniere’s disease among the 76 PVD patients. Conclusion We reported the incidence of dizziness/vertigo among Japanese primary care clinic patients, which was higher than that usually observed in the general population. Furthermore, we described the incidence of PVD and found that it was a major cause of dizziness/vertigo. PMID:25931828

  12. Prognostic stratification of patients with vasospastic angina: a comprehensive clinical risk score developed by the Japanese Coronary Spasm Association.

    PubMed

    Takagi, Yusuke; Takahashi, Jun; Yasuda, Satoshi; Miyata, Satoshi; Tsunoda, Ryusuke; Ogata, Yasuhiro; Seki, Atsushi; Sumiyoshi, Tetsuya; Matsui, Motoyuki; Goto, Toshikazu; Tanabe, Yasuhiko; Sueda, Shozo; Sato, Toshiaki; Ogawa, Satoshi; Kubo, Norifumi; Momomura, Shin-Ichi; Ogawa, Hisao; Shimokawa, Hiroaki

    2013-09-24

    The present study aimed to develop a comprehensive clinical risk score for vasospastic angina (VSA) patients. Previous studies demonstrated various prognostic factors of future adverse events in VSA patients. However, to apply these prognostic factors in clinical practice, the assessment of their accumulation in individual patients is important. The patient database of the multicenter registry study by the Japanese Coronary Spasm Association (JCSA) (n = 1,429; median 66 years; median follow-up 32 months) was utilized for score derivation. Multivariable Cox proportional hazard model selected 7 predictors of major adverse cardiac events (MACE). The integer score was assigned to each predictors proportional to their respective adjusted hazard ratio; history of out-of-hospital cardiac arrest (4 points), smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each), ST-segment elevation during angina, and beta-blocker use (1 point each). According to the total score in individual patients, 3 risk strata were defined; low (score 0 to 2, n = 598), intermediate (score 3 to 5, n = 639) and high (score 6 or more, n = 192). The incidences of MACE in the low-, intermediate-, and high-risk patients were 2.5%, 7.0%, and 13.0%, respectively (p < 0.001). The Cox model for MACE between the 3 risk strata also showed prognostic utility of the scoring system in various clinical subgroups. The average prediction rate of the scoring system in the internal training and validation sets were 86.6% and 86.5%, respectively. We developed a novel scoring system, the JCSA risk score, which may provide the comprehensive risk assessment and prognostic stratification for VSA patients. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. Differences in Clinical and Pathological Features of Renal Cell Carcinoma Between Japanese Patients After Kidney Transplantation and Those on Hemodialysis.

    PubMed

    Takagi, Toshio; Kondo, Tsunenori; Okumi, Masayoshi; Ishida, Hideki; Tanabe, Kazunari

    2017-04-01

    We compared the clinical features, pathological features, and prognoses of patients with renal cell carcinoma (RCC) arising in the native kidney after kidney transplantation (RCC-transplant) or on hemodialysis (RCC-HD), and analyzed predictive factors for survival at a Japanese single institution. This cohort included 42 patients in the RCC-transplant group and 467 patients in the RCC-HD group. RCC-transplant patients were younger (53 years vs. 56 years, P = 0.0358) and had less frequent symptoms (12% vs. 27%, P = 0.0344) than RCC-HD patients. Although tumor size, tumor stage, and histological subtype were not significantly different, the RCC-transplant group had less frequent multifocal occurrences and ACDK. Overall 5-year survival (RCC-transplant, 80%; RCC-hemodialysis, 76%; P = 0.3217) and 5-year cancer-specific survival (CSS; RCC-transplant, 84%; RCC-hemodialysis, 89%; P = 0.8916) were not significantly different between the two groups. Tumor stage and grade were significant predictors for CSS. Although kidney transplantation and hemodialysis were not associated with CSS, tumor stage was an independent predictor of CSS.

  14. Clinical Features of Japanese Patients with Central Retinal Vein Occlusion Complicated by Normal-Tension Glaucoma: A Retrospective Study.

    PubMed

    Kida, Teruyo; Fukumoto, Masanori; Sato, Takaki; Oku, Hidehiro; Ikeda, Tsunehiko

    2017-01-01

    The association of central retinal vein occlusion (CRVO) with primary open-angle glaucoma (POAG) or ocular hypertension has been reported, and lowering intraocular pressure (IOP) helps to improve the retinal circulation in eyes with CRVO. However, the clinical features of CRVOs with normal-tension glaucoma (NTG) are not well known. Therefore, we investigated Japanese CRVO patients with NTG. We retrospectively investigated 234 CRVO patients over 5 years, with follow-ups of more than 12 months, and evaluated the prevalence of glaucoma. Of the 234 CRVO patients, 18 (7.7%) were diagnosed with NTGs (n = 10) or POAGs (n = 8). Seven POAG (87.5%) and 3 NTG (30%) patients had systemic hypertension. At the initial CRVO evaluation, 6 NTGs showed a significantly increased IOP; mean IOP was 13.3 mm Hg before CRVO, 16.2 mm Hg at CRVO, and 13.5 mm Hg at the final visit. The proportion of NTGs with systemic hypertension was low. IOP of NTG patients was significantly elevated at the initial CRVO evaluation, even in the presence of anti-glaucoma drugs. © 2017 S. Karger AG, Basel.

  15. The reasons for triple therapy in stable COPD patients in Japanese clinical practice

    PubMed Central

    Miyazaki, Masaki; Nakamura, Hidetoshi; Takahashi, Saeko; Chubachi, Shotaro; Sasaki, Mamoru; Haraguchi, Mizuha; Terai, Hideki; Ishii, Makoto; Fukunaga, Koichi; Tasaka, Sadatomo; Soejima, Kenzo; Asano, Koichiro; Betsuyaku, Tomoko

    2015-01-01

    Background Triple combination therapy involving long-acting muscarinic antagonists long-acting β2 agonists, and inhaled corticosteroids has recently become an option for maintenance treatment of COPD. Some add-on clinical trials have reported the benefits of these combinations. However, the process to step up to triple therapy varies for individual cases. Methods Keio University and affiliated hospitals conducted an observational COPD cohort study, recruiting patients diagnosed as having COPD by pulmonary physicians and those referred for investigation of possible COPD. Their prescription history and clinical course were retrospectively analyzed based on the physicians’ medical records and patient questionnaires. This study was registered with UMIN (UMIN000003470, April 10, 2010). Results A total of 95 of the 445 COPD patients (21%) were treated with inhaled corticosteroids/long-acting β2 agonists/long-acting muscarinic antagonists as maintenance therapy, including 12 in COPD Grade I, 31 in Grade II, 38 in Grade III, and 14 in Grade IV, based on the Global Initiative for Chronic Obstructive Lung Disease spirometric grading. For more than half of the patients on triple therapy, the treatment had been intensified due to unsatisfactory improvement of symptoms, and 32% were treated with triple therapy due to comorbid asthma. In contrast, there were COPD patients whose therapy was maintained after starting with triple therapy because of their serious conditions or concurrent exacerbation at diagnosis (8%). Conclusion Triple therapy was often prescribed in the real-life management of COPD, even in patients whose airflow limitation was not severe. To better control symptoms was the major reason for choosing triple therapy, regardless of the severity of COPD, in Japan. PMID:26082629

  16. Clinical classification of 103 Japanese patients with Guillain-Barré syndrome.

    PubMed

    Br, Wakerley; Kokubun, N; Funakoshi, K; Nagashima, T; Hirata, K; Yuki, N

    2016-10-15

    Guillain-Barré syndrome (GBS) is the commonest cause of flaccid paralysis worldwide. Miller Fisher syndrome (MFS) is a variant of GBS characterized by ophthalmoplegia and ataxia. Together GBS and MFS form a continuum of discrete and overlapping subtypes, the frequency of which remains unknown. We retrospectively analysed the clinical features (antecedent symptoms, pattern of neurological weakness or ataxia, presence of hypersomnolence) of 103 patients at a single hospital in Japan. Patients were then classified according to new diagnostic criteria (Wakerley et al., 2014). Laboratory data (neurophysiology and anti-ganglioside antibody profiles) were also analysed. According to the new diagnostic criteria, the 103 patients could be classified as follows: classic GBS 73 (71%), pharyngeal-cervical-brachial weakness 2 (2%), acute pharyngeal weakness 0 (0%), paraparetic GBS 1 (1%), bifacial weakness with paraesthesias 1 (1%), polyneuritis cranialis 0 (0%), classic MFS 18 (17%), acute ophthalmoparesis 1 (1%), acute ptosis 0 (0%), acute mydriasis 0 (0%), acute ataxic neuropathy 1 (1%), Bickerstaff brainstem encephalitis 3 (3%), acute ataxic hypersomnolence 0 (0%), GBS and MFS overlap 1 (1%), GBS and Bickerstaff brainstem encephalitis overlap 1 (1%), MFS and pharyngeal-cervical-brachial weakness overlap 1 (1%). Application of the new clinical diagnostic criteria allowed accurate retrospective diagnosis and classification of GBS and MFS subtypes. Copyright © 2016. Published by Elsevier B.V.

  17. Clinical usefulness of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis

    PubMed Central

    Torisu, Yuichi; Nakano, Masanori; Takano, Keiko; Nakagawa, Ryo; Saeki, Chisato; Hokari, Atsushi; Ishikawa, Tomohisa; Saruta, Masayuki; Zeniya, Mikio

    2017-01-01

    AIM To evaluate the therapeutic effects of ursodeoxycholic acid (UDCA) on autoimmune hepatitis (AIH). METHODS A total 136 patients who were diagnosed with AIH were included in our study. All of the patients underwent a liver biopsy, and had at least a probable diagnosis on the basis of either the revised scoring system or the simplified scores. Initial treatment included UDCA monotherapy (Group U, n = 48) and prednisolone (PSL) monotherapy (Group P, n = 88). Group U was further classified into two subgroups according to the effect of UDCA: Patients who had achieved remission induction with UDCA monotherapy and showed no sign of relapse (Subgroup U1, n = 34) and patients who additionally received PSL during follow-up (Subgroup U2, n = 14). We compared the clinical and histological findings between each groups, and investigated factors contributing to the response to UDCA monotherapy. RESULTS In Group U, 34 patients (71%) achieved and maintained remission over 49 (range: 8-90) mo (Subgroup U1) and 14 patients (29%) additionally received PSL (Subgroup U2) during follow-up. Two patients in Subgroup U2 achieved remission induction once but additionally required PSL administration because of relapse (15 and 35 mo after the start of treatment). The remaining 12 patients in Subgroup U2 failed to achieve remission induction during follow-up, and PSL was added during 7 (range: 2-18) mo. Compared with Subgroup U2, Subgroup U1 had significantly lower alanine aminotransferase (ALT) levels at onset (124 IU/L vs 262 IU/L, P = 0.023) and a significantly higher proportion of patients with mild inflammation (A1) on histological examination (70.6% vs 35.7%, P = 0.025). When multivariate analysis was performed to identify factors contributing to the response to UDCA monotherapy, only a serum ALT level of 200 IU/L or lower was found to be associated with a significant difference (P = 0.013). CONCLUSION To prevent adverse events related to corticosteroids, UDCA monotherapy for AIH needs

  18. Clinical utility of erlotinib for the treatment of non-small-cell lung cancer in Japanese patients: current evidence

    PubMed Central

    Togashi, Yosuke; Hayashi, Hidetoshi; Nakagawa, Kazuhiko; Nishio, Kazuto

    2014-01-01

    Gefitinib, an epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI), has been approved in Japan for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) based on Phase II clinical trials since 2002. Erlotinib, another EGFR-TKI, was also approved a few years thereafter. In 2004, activating mutations in the EGFR gene were discovered to be a predictive biomarker for EGFR-TKI treatment, and gefitinib, which is not effective for patients with EGFR wild-type NSCLC, has since been used only in patients with EGFR-mutated NSCLC. In contrast, erlotinib is potentially effective for the treatment of EGFR wild-type NSCLC. Similar to gefitinib, erlotinib is also effective for EGFR-mutated NSCLC and has been used as an initial treatment for patients with advanced EGFR-mutated NSCLC. Both gefitinib and erlotinib can be used in a Japanese clinical setting. The approved daily dose of erlotinib (150 mg) is equal to the maximum tolerated dose of erlotinib. In contrast, the daily dose of gefitinib has been set at 250 mg, which is approximately one-third of the maximum tolerated dose of gefitinib. Accordingly, a higher serum concentration can be achieved using erlotinib, compared with gefitinib. This advantage can be applied to the treatment of central nervous system metastases (brain metastasis and carcinomatous meningitis), the treatment of which is complicated by the difficulty drugs have penetrating the blood–brain barrier. Although patients with EGFR-mutated NSCLC respond dramatically to EGFR-TKIs, some patients have a poor response and the majority eventually undergo disease progression. To overcome such resistance, several novel treatment strategies, such as combination therapy and next-generation EGFR-TKIs, have been attempted. PMID:25114510

  19. Clinical Phenotype Classifications Based on Static Varus Alignment and Varus Thrust in Japanese Patients With Medial Knee Osteoarthritis

    PubMed Central

    Iijima, Hirotaka; Fukutani, Naoto; Fukumoto, Takahiko; Uritani, Daisuke; Kaneda, Eishi; Ota, Kazuo; Kuroki, Hiroshi; Matsuda, Shuichi

    2015-01-01

    Objective To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA). Methods Patients in an orthopedic clinic (n = 266) diagnosed as having knee OA (Kellgren/Lawrence [K/L] grade ≥1) were divided into 4 phenotype groups according to the presence or absence of static varus alignment and varus thrust (dynamic varus): no varus (n = 173), dynamic varus (n = 17), static varus (n = 50), and static varus + dynamic varus (n = 26). The knee range of motion, spatiotemporal gait parameters, visual analog scale scores for knee pain, and scores on the Japanese Knee Osteoarthritis Measure were used to assess clinical outcomes. Multiple logistic regression analyses identified the relationship between knee pain during gait and the 4 phenotypes, adjusted for possible risk factors, including age, sex, body mass index, K/L grade, and gait velocity. Results Multiple logistic regression analysis showed that varus thrust without varus alignment was associated with knee pain during gait (odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.08–12.4), and that varus thrust combined with varus alignment was strongly associated with knee pain during gait (OR 17.1, 95% CI 3.19–320.0). Sensitivity analyses applying alternative cutoff values for defining static varus alignment showed comparable results. Conclusion Varus thrust with or without static varus alignment was associated with the occurrence of knee pain during gait. Tailored interventions based on individual malalignment phenotypes may improve clinical outcomes in patients with knee OA. PMID:26017348

  20. Clinical evidence for Japanese population based on prospective studies--linking clinical trials and clinical practice.

    PubMed

    Ogawa, Hisao; Kojima, Sunao

    2009-10-01

    "Evidence-based medicine (EBM)" implies effective and high quality practice for patients based on well-grounded medical science. The success of clinical trials in Japan is essential to build original evidence specific for Japanese patients. Based on this concept, we have performed several large-scale clinical trials to provide EBM, including the Japanese Antiplatelets Myocardial Infarction Study [JAMIS; clinical improvement in acute myocardial infarction (AMI) patients with antiplatelet therapy], the Japanese beta-Blockers and Calcium Antagonists Myocardial Infarction (JBCMI; comparison of the effects of beta-blockers and calcium antagonists on cardiovascular events in post-AMI patients), a multicenter study for aggressive lipid-lowering strategy by HMG-CoA reductase inhibitors in patients with AMI (MUSASHI; effects of statin therapy on cardiovascular events in patients with AMI), and the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD trial; efficacy of low-dose aspirin therapy for primary prevention of atherosclerotic events in type 2 diabetic patients). The results of these prospective studies were directly linked with clinical practice. We have acquired the know-how of large-scale clinical trials; an important point is to have passion for "buildup evidence specific for the Japanese" and to recruit subjects for enrollment after explaining the significance of "clinical trials for the Japanese".

  1. The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study.

    PubMed

    Nakamura, Tomoki; Matsumine, Akihiko; Kawai, Akira; Araki, Nobuhito; Goto, Takahiro; Yonemoto, Tsukasa; Sugiura, Hideshi; Nishida, Yoshihiro; Hiraga, Hiroaki; Honoki, Kanya; Yasuda, Taketoshi; Boku, Shogen; Sudo, Akihiro; Ueda, Takafumi

    2016-05-01

    Because the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large-scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real-life, postmarketing surveillance data. Patients received pazopanib with the objective of treating local recurrence (n = 20), metastasis (n = 104), and both (n = 32). The patient median age was 53.8 years. The primary objective of this study was to clarify the efficacy of pazopanib for patients with STS. The median treatment duration was 28.7 weeks, and the average dose intensity of pazopanib was 609 mg. Adverse events occurred in 127 patients (81.4%). In addition to the main common toxicities, such as hypertension and liver disorder, pneumothorax (n = 11) and thrombocytopenia (n = 16) also were observed. The median progression-free survival for all patients was 15.4 weeks. The median progression-free survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 18.6 weeks, 16.4 weeks, 15.3 weeks, and 8 weeks, respectively. The median survival for all patients was 11.2 months. The median survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 20.1 months, 10.6 months, 9.5 months, and 7.3 months, respectively. There were apparent differences in the efficacy of pazopanib treatment among histologic types of STS. Pazopanib treatment is a new treatment option; however, adverse events like pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study (pazopanib for metastatic soft-tissue sarcoma), should be taken into consideration. Cancer 2016;122:1408-16. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. © 2016 The Authors. Cancer published by Wiley

  2. Clinical symptoms of FSSG in gastroesophageal reflux disease are critical for PPI treatment: Japanese multi-centers with 185 patients.

    PubMed

    Komatsu-Tanaka, Mio; Iwakiri, Ryuichi; Fujimoto, Kazuma; Fujiwara, Yasuhiro; Inamori, Masahiko; Tanaka, Junji; Shimatani, Tomohiko; Akiyama, Junichi; Ando, Takashi; Manabe, Noriaki; Kinjo, Fukunori; Deguchi, Ryuzo; Kusano, Motoyasu

    2012-11-01

    The main aim of this study was to determine whether questionnaire evaluations of clinical symptoms in gastroesophageal reflux disease were useful to assess proton pump inhibitor therapy. A total of 185 Japanese patients (men, 88; women, 97; age: 55.7 ± 16.1 years) with gastroesophageal reflux disease were enrolled. The patients were divided based on the frequency scale for symptoms of gastroesophageal reflux disease: severe symptoms with scores ≥8 and mild symptoms with scores ≤7. Quality of life was evaluated with the Medical Outcomes Study 8-Item Short-Form Health Survey. All patients were treated with a proton pump inhibitor, rabeprazole (10 mg/day), for 8 weeks. Patients were classified into four groups: reflux esophagitis with severe symptoms (n = 92, 49.7%); reflux esophagitis with mild symptoms (n = 17, 9.2%); non-erosive reflux disease with severe symptoms (n = 66, 35.7%); and non-erosive reflux disease with mild symptoms (n = 10, 5.4%). The dysmotility score was high in non-erosive reflux disease with severe symptoms compared with reflux esophagitis with severe symptoms (9.1 ± 0.5 vs 6.8 ± 0.5, P < 0.05). The symptom score and quality of life in the severe symptoms groups for both reflux esophagitis and non-erosive reflux disease were significantly improved by rabeprazole treatment. Only the reflux score was improved by rabeprazole in the reflux esophagitis with mild symptoms group; no therapeutic effect was observed for the non-erosive reflux disease with mild symptoms group. Low scores on the frequency scale for the symptoms of gastroesophageal reflux disease indicate poor responsiveness to proton pump inhibitor treatment, and high scores indicate good responsiveness. © 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.

  3. Clinical characteristics of seven patients with Aeromonas septicemia in a Japanese hospital.

    PubMed

    Morinaga, Yoshitomo; Yanagihara, Katsunori; Araki, Nobuko; Harada, Yosuke; Yamada, Koichi; Akamatsu, Norihiko; Matsuda, Junichi; Nishino, Tomoya; Hasegawa, Hiroo; Izumikawa, Koichi; Kakeya, Hiroshi; Yamamoto, Yoshihiro; Yasuoka, Akira; Kohno, Shigeru; Kamihira, Shimeru

    2011-10-01

    The genus Aeromonas comprises flagellated gram-negative rods widely distributed in freshwater, estuarine and marine environments. Aeromonas species may cause a variety of illnesses in humans, such as enterocolitis and septicemia, especially in warmer tropical or subtropical environments. To recognize the characteristics of Aeromonas septicemia in Japan, we reviewed laboratory data and medical records in our hospital. During 11 years (from 2000 to 2010), Aeromonas septicemia was observed in seven patients involving six female subjects. Six patients were observed in summer or fall. The incidence of Aeromonas septicemia was about 0.07 per 1000 admissions, and two out of the seven patients died. All patients had underlying diseases such as malignancy (six patients) and choledocholithiasis (one patient). Two patients developed septicemia within two days after ingesting raw seafood. Five patients developed Aeromonas septicemia > 48 h after admission. Fever was present in all patients, and four out of the seven patients developed septic shock. All patients developed monomicrobial septicemia. A. hydrophila was isolated from five patients, and A. caviae and A. veronii biovar sobria were isolated from one patient each. Most antimicrobial agents had high activity against the isolated strains. However, a carbapenem-resistant strain appeared in one patient during treatment and led to death. Aeromonas septicemia is uncommon in temperate areas but can occur particularly in warm seasons. Immunocompromised conditions and recent ingestion of raw fish or shellfish are important characteristics of developing Aeromonas septicemia.

  4. Clinical Features and Outcomes of IPF Patients Hospitalized for Pulmonary Infection: A Japanese Cohort Study

    PubMed Central

    Yamazaki, Ryo; Nishiyama, Osamu; Sano, Hiroyuki; Iwanaga, Takashi; Higashimoto, Yuji; Kume, Hiroaki; Tohda, Yuji

    2016-01-01

    Many patients with idiopathic pulmonary fibrosis (IPF) undergo hospitalizations due to pulmonary infections. We retrospectively investigated the characteristics of hospitalizations due to pulmonary infection in patients with IPF to elucidate causative pathogens and mortality. We reviewed patients with IPF who were admitted between January 2008 and December 2014 for pulmonary infections including pneumonia and bronchitis. The causative pathogen, the relationship between the site of pneumonia and existing IPF radiological patterns on high-resolution chest CT, and predictors of mortality were evaluated. Forty-eight IPF patients were hospitalized a totally of 81 times due to pulmonary infection during the study period. In the 48 first-time admissions after IPF diagnosis, causative pathogens were detected in 20 patients (41.6%). The most common pathogen was Haemophilus influenzae (14.5%) followed by Pseudomonas aeruginosa (4.1%), Staphylococcus aureus (4.1%), Branhamella catarrhalis (4.1%), and Klebsiella pneumoniae (4.1%). Among all 81 admissions, the most common pathogen was P. aeruginosa (12.3%), followed by H. influenzae (8.6%), S. aureus (6.1%) and Escherichia coli (4.9%). No relationship was observed between the detected pathogen and the site of pneumonia. The 30-day and hospital mortality rates were 14.5% and 18.7%, respectively. Pneumonia severity index on admission was significantly associated with both 30-day and hospital mortality. In conclusion, IPF patients hospitalized for pulmonary infections had high 30-day and hospital mortality. In contrast to community-acquired pneumonia, the causative pathogens mainly consisted of gram-negative bacteria. The PSI score may be a significant predictor of mortality. These results provide information for empiric antibiotic selection when treating IPF patients with pulmonary infections. PMID:27959904

  5. Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: a Japanese phase 2 clinical trial.

    PubMed

    Matsumoto, Yukihiro; Ohashi, Yuichi; Watanabe, Hitoshi; Tsubota, Kazuo

    2012-10-01

    To investigate the dose-dependent efficacy and safety of diquafosol ophthalmic solution for the treatment of dry eye syndrome. Randomized, double-masked, multicenter, parallel-group, placebo-controlled trial. A total of 286 Japanese patients with dry eye who were prescribed topical diquafosol (1%, n = 96; 3%, n = 96) or placebo ophthalmic solution (n = 94). After a washout period of 2 weeks, qualified subjects were randomized to receive a single drop of 1% or 3% diquafosol or placebo ophthalmic solutions 6 times per day for 6 weeks. The primary outcome measure was fluorescein corneal staining score assessment. The secondary outcome measures were Rose Bengal corneal and conjunctival staining scores, tear break-up time (BUT), and subjective symptom assessment. Safety measures were clinical blood and urine examination and recording of adverse events. Fluorescein corneal staining scores significantly improved with both 1% and 3% topical diquafosol compared with placebo at 4 weeks, respectively (P = 0.037, P = 0.002). There was a dose-dependent effect among the groups. Rose Bengal corneal and conjunctival staining scores also improved significantly with both 1% and 3% diquafosol compared with placebo (P = 0.007 and P = 0.004, respectively). Subjective dry eye symptom scores significantly improved with both diquafosol ophthalmic solutions (P ≤ 0.033), although there were no significant differences in BUT compared with placebo. No significant differences between the treatment groups were observed in relation to the occurrence of adverse events. Both 1% and 3% diquafosol ophthalmic solutions are considered effective and safe for the treatment of dry eye syndrome. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  6. Clinical manifestations of Japanese encephalitis in southern Taiwan.

    PubMed

    Chen, Kuang Ming; Tsai, Hung Chin; Sy, Cheng Len; Lee, Susan Shin-Jung; Liu, Yung Ching; Wann, Shue Ren; Wang, Yung Hsing; Mai, Ming Hsin; Chen, Jei Kuang; Wu, Kuan Sheng; Chen, Yi Jan; Chen, Yao Shen

    2009-08-01

    Japanese encephalitis virus infection is a sporadic infectious disease in Taiwan. Despite progress in laboratory examinations and imaging studies, diagnosis of Japanese encephalitis remains underestimated. This study was conducted to identify clinical symptoms and laboratory findings that may assist in early identification of this disease. This retrospective study included all patients diagnosed with Japanese encephalitis at Kaohsiung Veterans General Hospital from January 2000 through December 2007. Epidemiologic data, predisposing factors, neurological and non-neurological signs and symptoms, laboratory data, and treatment were analyzed. Outcomes and neurological complications were evaluated. Eleven patients had Japanese encephalitis, and 10 had sufficient information for enrolment into the study. Nine patients presented with non-significant constitutional symptoms of fever, nausea, or headache. Other signs and symptoms included rhinorrhea, sore throat, abdominal pain, cough, myalgia, or arthralgia. Eight patients had lymphocytic pleocytosis with elevated protein and borderline low glucose levels in the cerebrospinal fluid. Leptomeningeal enhancement and low density lesions were the most common computed tomography findings. T2 hyperintensity lesions and leptomeningeal enhancement were seen in 5 patients. Two patients presenting with acute flaccid paralysis had high intensity lesions on the thalamus and basal ganglion. There were no correlations between clinical, laboratory, and imaging findings. None of the patients had neurological sequelae. Presentations, laboratory examination, and clinical signs are not specific for Japanese encephalitis. Sporadic cases are usually seen from May to August, which are associated with monsoon rains. Hence increased awareness of this disease is recommended during these periods.

  7. Pancreatic safety in Japanese patients with type 2 diabetes treated with once weekly dulaglutide 0.75 mg up to 52 weeks in phase 3 clinical trials.

    PubMed

    Emoto, Masanori; Oura, Tomonori; Matsui, Akiko; Kazama, Hirotaka; Iwamoto, Noriyuki

    2017-02-27

    The effects of incretin therapies on pancreatic safety are currently being evaluated. In 3 phase 3 clinical studies of once weekly dulaglutide 0.75 mg (dulaglutide) in Japanese patients with type 2 diabetes (T2D), symptoms suggestive of acute pancreatitis as well as pancreatic enzymes were assessed and the risk of acute pancreatitis was evaluated. Patients who met any of the predefined criteria (clinical signs/symptoms of acute pancreatitis, confirmed amylase or lipase level ≥3 times the upper limit of normal [ULN], abdominal imaging of the pancreas) were adjudicated for acute pancreatitis by a blinded external committee. A total of 43 events in 40 patients (dulaglutide, 35/917 patients; liraglutide, 2/137 patients; insulin glargine, 2/180 patients; and placebo, 2/70 patients) were adjudicated (1 patient had events adjudicated during both placebo and dulaglutide treatment); 2 patients treated with dulaglutide had acute pancreatitis confirmed (2/917 [0.2%]; 2.651 patients/1,000 patient-years). One of these patients was diagnosed by the investigator with acute pancreatitis related to dulaglutide, but there was no typical abdominal pain. The event in the other patient occurred following an endoscopic ultrasound-guided fine needle aspiration. Transient increases in lipase ≥3×ULN were observed in 2% of patients in both the dulaglutide and liraglutide groups; the incidence in dulaglutide-treated patients was not significantly different from the incidences in liraglutide, placebo-, or insulin glargine-treated patients. Results of systematic assessments of pancreatic safety in 3 phase 3 studies for up to 52 weeks do not suggest an increased risk of acute pancreatitis in Japanese patients treated with dulaglutide.

  8. Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe/USA: genetic and clinical studies of 86 unrelated patients with low-molecular-weight proteinuria.

    PubMed

    Sekine, Takashi; Komoda, Fusako; Miura, Kenichiro; Takita, Junko; Shimadzu, Mitsunobu; Matsuyama, Takeshi; Ashida, Akira; Igarashi, Takashi

    2014-02-01

    Dent disease is an X-linked disorder characterized by low-molecular-weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, urolithiasis and renal dysfunction. Dent disease is caused by mutations in at least two genes, i.e. CLCN5 and OCRL1, and its genetic background and phenotypes are common among European countries and the USA. However, only few studies on Dent disease in Japan, which was originally called 'low-molecular-weight proteinuric disease', have been reported thus far. In this study, we analysed genetic background and clinical phenotype and laboratory data of 86 unrelated Japanese Dent disease patients. The results demonstrated that the genetic basis of Japanese Dent disease was nearly identical to those of Dent disease in other countries. Of 86 unrelated Japanese Dent patients, 61 possessed mutations in CLCN5 (Dent-1), of which 27 were novel mutations; 11 showed mutations in OCRL1 (Dent-2), six of which were novel, and the remaining 14 patients showed no mutations in CLCN5 or OCRL1 (Dent-NI). Despite the similarity in genetic background, hypercalciuria was detected in only 51%, rickets in 2% and nephrocalcinosis in 35%. Although the patients were relatively young, six patients (8%) showed apparent renal dysfunction. Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe and the USA.

  9. Fifty-two-week long-term clinical study of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise.

    PubMed

    Seino, Yutaka; Kaku, Kohei; Inagaki, Nobuya; Haneda, Masakazu; Sasaki, Takashi; Fukatsu, Atsushi; Ubukata, Michito; Sakai, Soichi; Samukawa, Yoshishige

    2015-01-01

    Luseogliflozin, a selective sodium glucose cotransporter 2 inhibitor, was demonstrated in a previous 24-week study of type 2 diabetic patients to be efficacious and well tolerated. This study mainly aimed to evaluate the long-term safety of luseogliflozin monotherapy in Japanese type 2 diabetic patients based on the Japanese guidelines. Additionally, long-term efficacy was also evaluated. Patients on diet and exercise therapy alone with an HbA1c of 6.9-10.5% received luseogliflozin 2.5 mg once daily for 52 weeks. For patients with insufficient glycemic control, this dose was able to be increased to 5 mg at Week 24. Adverse events (AEs), clinical laboratory tests, vital signs and 12-lead electrocardiograms were used to assess safety. Efficacy endpoints consisted of changes in HbA1c, fasting plasma glucose (FPG), and body weight from baseline. Of 299 patients who received luseogliflozin, 279 completed the study. Most AEs were mild in severity with incidences of AEs and adverse drug reactions at 75.3% and 16.7%, respectively. Although hypoglycemia was observed in 7 patients (2.3%), no major hypoglycemic episodes occurred. The incidences of AEs of special interest, including pollakiuria, volume depletion and urinary tract/genital infections, were at acceptable levels. Luseogliflozin significantly lowered HbA1c (-0.50%, P< 0.001), FPG (-16.3 mg/dL, P< 0.001) and body weight (-2.68 kg, P< 0.001) at Week 52 compared to baseline. Up-titration to 5 mg further improved glycemic control. In this long-term study of Japanese type 2 diabetic patients, luseogliflozin monotherapy was well tolerated for 52 weeks and provided a sustained glycemic lowering effect and reduced body weight.

  10. Clinical characteristics of silent myocardial ischemia diagnosed with adenosine stress 99mTc-tetrofosmin myocardial scintigraphy in Japanese patients with acute cerebral infarction.

    PubMed

    Nomura, Tetsuya; Kusaba, Tetsuro; Kodama, Naotoshi; Terada, Kensuke; Urakabe, Yota; Nishikawa, Susumu; Keira, Natsuya; Matsubara, Hiroaki; Tatsumi, Tetsuya

    2013-01-01

    It is well known that silent myocardial ischemia (SMI) often complicates patients with cerebral infarction and that stroke patients often die of ischemic heart disease. Therefore, it is considered important to treat myocardial ischemia in stroke patients. This study investigated SMI complicating Japanese patients with fresh stroke, using (99m)Tc-tetrofosmin myocardial scintigraphy with pharmacologic stress testing to elucidate their clinical manifestations. This study included 41 patients (26 men, mean age 76.0 ± 10.7 years) with acute cerebral infarction and no history of coronary artery disease. All patients underwent (99m)Tc-tetrofosmin myocardial scintigraphy with intravenous administration of adenosine to diagnose SMI. Of the 41 patients, myocardial ischemia was confirmed in 17 patients (41.5%). Atherosclerotic etiology was the major cause of stroke in the ischemia(+) group and embolic origin was the major cause in the ischemia(-) group. Patients with myocardial ischemia had a higher incidence of diabetes mellitus (52.9 vs 20.8%; P = 0.0323) and more than two conventional cardiovascular risk factors (64.7 vs 25.0%; P = 0.0110) compared with the nonischemic patients. Infarction subtype of atherosclerotic origin was an independent positive predictor of asymptomatic myocardial ischemia in patients with stroke. These findings indicate that the prevalence of asymptomatic myocardial ischemia is relatively high, especially in patients with stroke of atherosclerotic origin. Therefore, it is beneficial for us to narrow the target population who are at the highest risk when screening for SMI in Japanese patients with acute cerebral infarction.

  11. CORRIGENDUM: Clinical Presentation, Management and Outcome of Japanese Patients With Acute Myocardial Infarction in the Troponin Era--Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET).

    PubMed

    Ishihara, Masaharu; Fujino, Masashi; Ogawa, Hisao; Yasuda, Satoshi; Noguchi, Teruo; Nakao, Koichi; Ozaki, Yukio; Kimura, Kazuo; Suwa, Satoru; Fujimoto, Kazuteru; Nakama, Yasuharu; Morita, Takashi; Shimizu, Wataru; Saito, Yoshihiko; Tsujita, Kennichi; Nishimura, Kunihiko; Miyamoto, Yoshihiro

    2015-01-01

    The authors apologize for the incorrect statement in the Methods section. The correct statement is shown below. Page 1256, right column, lines 10–12: Incorrect: Consecutive patients hospitalized within 48 h of onset of AMI at 28 Japanese medical institutions were enrolled between July 2013 and May 2014. Correct: Consecutive patients hospitalized within 48 h of onset of AMI at 28 Japanese medical institutions were enrolled between July 2012 and March 2014.

  12. Clinical outcomes and causes of death in Japanese patients with long-term inferior vena cava filter implants and deep vein thrombosis.

    PubMed

    Iwamoto, Yumiko; Okamoto, Mitsunori; Hashimoto, Masaki; Fukuda, Yukihiro; Uchimura, Yuko; Iwamoto, Akimichi; Matsumoto, Takeshi; Iwasaki, Toshitaka; Kinoshita, Hiroki; Ueda, Hironori; Kihara, Yasuki

    2014-10-01

    We assessed the causes of death and efficacy of permanent inferior vena cava (IVC) filters for preventing new pulmonary embolisms (PE) in Japanese deep vein thrombosis (DVT) patients with or without PE. We studied the clinical outcomes during the follow-up period of 1 day to 9 years (median: 18 months; mean: 28 months) in 66 of 72 consecutive patients (44 with acute PE, 27 with intrapelvic DVT, and 1 with floating femoral vein thrombosis). Fifty of 66 patients received anticoagulant therapy after the filter placement. Five patients died within 1 month (median 9 days) after the filter placement: three from recurrence of PE, one from cancer, and one from sepsis. Two of the three patients with recurrence of PE had preexisting intracardiac thrombi in the right atrium or main pulmonary artery before filter implantation. Ten patients died from the underlying disease (cancer: 7; brain hemorrhage: 1; amyotrophic lateral sclerosis: 1; pneumonia: 1) over 1 month after the filter placement (median follow-up period: 21 months). No new symptomatic PE recurrence was observed over 1 month after the filter placement. The 61 patients with long-term follow-up had no deterioration of DVT, and all the 31 patients who underwent multi-slice computed tomography showed no PE recurrence or filter thrombus occlusion, fracture, or migration. Underlying diseases and preexisting intracardiac thrombi may be the determining factors for the prognosis of DVT patients. Permanent IVC filters with anticoagulant therapy may be effective for preventing death from new PE in Japanese DVT patients. Copyright © 2014. Published by Elsevier Ltd.

  13. Japanese Society of Medical Oncology Clinical Guidelines: RAS (KRAS/NRAS) mutation testing in colorectal cancer patients11

    PubMed Central

    Taniguchi, Hiroya; Yamazaki, Kentaro; Yoshino, Takayuki; Muro, Kei; Yatabe, Yasushi; Watanabe, Toshiaki; Ebi, Hiromichi; Ochiai, Atsushi; Baba, Eishi; Tsuchihara, Katsuya

    2015-01-01

    The Japanese guidelines for the testing of KRAS mutations in colorectal cancer have been used for the past 5 years. However, new findings of RAS (KRAS/NRAS) mutations that can further predict the therapeutic effects of anti-epidermal growth factor receptor (EGFR) antibody therapy necessitated a revision of the guidelines. The revised guidelines included the following five basic requirements for RAS mutation testing to highlight a patient group in which anti-EGFR antibody therapy may be ineffective: First, anti-EGFR antibody therapy may not offer survival benefit and/or tumor shrinkage to patients with expanded RAS mutations. Thus, current methods to detect KRAS exon 2 (codons 12 and 13) mutations are insufficient for selecting appropriate candidates for this therapy. Additional testing of extended KRAS/NRAS mutations is recommended. Second, repeated tests are not required for the detection; tissue materials of either primary or metastatic lesions are applicable for RAS mutation testing. Evaluating RAS mutations prior to anti-EGFR antibody therapy is recommended. Third, direct sequencing with manual dissection or allele-specific PCR-based methods is currently applicable for RAS mutation testing. Fourth, thinly sliced sections of formalin-fixed, paraffin-embedded tissue blocks are applicable for RAS mutation testing. One section stained with H&E should be provided to histologically determine whether the tissue contains sufficient amount of tumor cells for testing. Finally, RAS mutation testing must be performed in laboratories with appropriate testing procedures and specimen management practices. PMID:25800101

  14. Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes stratified by body mass index: A subgroup analysis of five randomized clinical trials.

    PubMed

    Kashiwagi, Atsunori; Yoshida, Satoshi; Nakamura, Ichiro; Kazuta, Kenichi; Ueyama, Eiji; Takahashi, Hideyuki; Satomi, Hayato; Kosakai, Yoshinori; Kawamuki, Kosei

    2016-07-01

    The influence of overweight/obesity on the clinical efficacy and safety of sodium-glucose co-transporter 2 inhibitors is unclear. We carried out a pooled analysis to examine the impact of body mass index on the efficacy and safety of ipragliflozin. Patient-level data were pooled for five Japanese double-blind trials (NCT00621868, NCT01057628, NCT01135433, NCT01225081 and NCT01242215) in which patients were randomized to ipragliflozin or a placebo as monotherapy, or in combination with metformin, pioglitazone or a sulfonylurea. Outcomes included the changes in hemoglobin A1c, fasting plasma glucose, bodyweight and treatment-emergent adverse events. Patients were divided into four body mass index categories. Hemoglobin A1c, fasting plasma glucose and bodyweight decreased significantly in the ipragliflozin group compared with the placebo group in all body mass index categories, and in the total cohort (all P < 0.001). Hemoglobin A1c did not improve in 11.2 and 69.2% of patients in the ipragliflozin and placebo groups, respectively. The change in hemoglobin A1c was weakly correlated with the change in bodyweight in all patients (r = 0.136, P = 0.002). Regarding laboratory variables, the placebo-subtracted difference tended to be greater in patients with higher body mass index for aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase and uric acid. The incidences of treatment-emergent adverse events were similar between the ipragliflozin and placebo groups in all patients combined and in the four body mass index categories. These results show that the efficacy and safety of ipragliflozin are not influenced by obesity/overweight in Japanese patients. © 2015 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  15. Net clinical benefit of rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation: a subgroup analysis of J-ROCKET AF.

    PubMed

    Uchiyama, Shinichiro; Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

    2014-01-01

    The risk factors that have been identified for bleeding events with rivaroxaban are predominantly the same as those predicting thromboembolic ones in patients with atrial fibrillation (AF). Our aim was to determine the net clinical benefit (NCB) from the results of the J-ROCKET AF trial, in which rivaroxaban was compared with warfarin in Japanese patients with AF. Two strategies were adopted to quantify the NCB. First, the NCB was calculated as the number of ischemic strokes avoided with anticoagulation minus the number of excess intracranial hemorrhage (ICH) with a weight of 1.5. Second, the composite end point of major bleeding events and secondary efficacy end points (stroke, noncentral nervous system systemic embolism, myocardial infarction and death) to ascertain the NCB were established. Subgroup analysis by CHADS2 score or creatinine clearance was also performed. The adjusted NCB, which was given a weight of 1.5 for ICH, was nominally significant in favor of rivaroxaban therapy (difference in incidence rate -2.13; 95% confidence interval [CI]: -.26 to -3.99). Furthermore, the event rate of the composite end point tended to be lower in patients treated with rivaroxaban than in those treated with warfarin (rivaroxaban: 4.97% per year, warfarin: 6.11% per year; difference in incidence rate: -1.14; 95% CI: -3.40 to 1.12). The event rate of the composite end point tended to be consistently low in patients treated with rivaroxaban in the subanalysis by CHADS2 score and renal function. Analysis of the NCB supports that rivaroxaban therapy provides clinical benefit for Japanese patients with AF. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Clinical assessment of a supplement of Pycnogenol® and L-arginine in Japanese patients with mild to moderate erectile dysfunction.

    PubMed

    Aoki, Hiromitsu; Nagao, Junji; Ueda, Taro; Strong, Jeffry M; Schonlau, Frank; Yu-Jing, Song; Lu, Yan; Horie, Shigeo

    2012-02-01

    A double-blind parallel group comparison design clinical study was conducted in Japanese patients with mild to moderate erectile dysfunction to investigate the efficacy of a supplement containing Pycnogenol® and L-arginine. Subjects were instructed to take a supplement (Pycnogenol® 60 mg/day, L-arginine 690 mg/day and aspartic acid 552 mg/day) or an identical placebo for 8 weeks, and the results were assessed using the five-item erectile domain (IIEF-5) of the International Index of Erectile Function. Additionally, blood biochemistry, urinalysis and salivary testosterone were measured. Eight weeks of supplement intake improved the total score of the IIEF-5. In particular, a marked improvement was observed in 'hardness of erection' and 'satisfaction with sexual intercourse'. A decrease in blood pressure, aspartate transaminase and γ-glutamyl transpeptidase (γ-GTP), and a slight increase in salivary testosterone were observed in the supplement group. No adverse reactions were observed during the study period. In conclusion, Pycnogenol® in combination with L-arginine as a dietary supplement is effective and safe in Japanese patients with mild to moderate erectile dysfunction.

  17. Clinical and mutational spectrum of Japanese patients with Charcot-Marie-Tooth disease caused by GDAP1 variants.

    PubMed

    Yoshimura, A; Yuan, J-H; Hashiguchi, A; Hiramatsu, Y; Ando, M; Higuchi, Y; Nakamura, T; Okamoto, Y; Matsumura, K; Hamano, T; Sawaura, N; Shimatani, Y; Kumada, S; Okumura, Y; Miyahara, J; Yamaguchi, Y; Kitamura, S; Haginoya, K; Mitsui, J; Ishiura, H; Tsuji, S; Takashima, H

    2017-09-01

    Mutations in GDAP1 are responsible for heterogeneous clinical and electrophysiological phenotypes of Charcot-Marie-Tooth disease (CMT), with autosomal dominant or recessive inheritance pattern. The aim of this study is to identify the clinical and mutational spectrum of CMT patients with GDAP1 variants in Japan. From April 2007 to October 2014, using three state-of-art technologies, we conducted gene panel sequencing in a cohort of 1,030 patients with inherited peripheral neuropathies (IPNs), and 398 mutation-negative cases were further analyzed with whole-exome sequencing. We identified GDAP1 variants from 10 patients clinically diagnosed with CMT. The most frequent recessive variant in our cohort (5/10), c.740C>T (p.A247V), was verified to be associated with a founder event. We also detected three novel likely pathogenic variants: c.928C>T (p.R310W) and c.546delA (p.E183Kfs*23) in Case 2 and c.376G>A (p.E126K) in Case 8. Nerve conduction study or sural nerve biopsy of all 10 patients indicated axonal type peripheral neuropathy. We identified GDAP1 variants in approximately 1% of our cohort with IPNs, and established a founder mutation in half of these patients. Our study originally described the mutational spectrum and clinical features of GDAP1-related CMT patients in Japan. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Gender differences in the clinical characteristics and outcomes of patients with vasospastic angina--a report from the Japanese Coronary Spasm Association.

    PubMed

    Kawana, Akiko; Takahashi, Jun; Takagi, Yusuke; Yasuda, Satoshi; Sakata, Yasuhiko; Tsunoda, Ryusuke; Ogata, Yasuhiro; Seki, Atsushi; Sumiyoshi, Tetsuya; Matsui, Motoyuki; Goto, Toshikazu; Tanabe, Yasuhiko; Sueda, Shozo; Kubo, Norifumi; Momomura, Shin-ichi; Ogawa, Hisao; Shimokawa, Hiroaki

    2013-01-01

    Accumulating evidence has demonstrated the gender differences in the clinical characteristics and outcomes of patients with ischemic heart disease. However, it remains to be elucidated whether it is also the case for vasospastic angina (VSA). We enrolled a total of 1,429 VSA patients (male/female, 1090/339; median age 66 years) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. As compared with male patients, female patients were characterized by older age (median 69 vs. 66 years), lower incidence of smoking (20% vs. 72%) and less significant organic stenosis (9% vs. 16%) (all P=0.001). Multivariate analysis demonstrated that the predictors of major adverse cardiac events (MACE) were considerably different by genders; women were more associated with age and electrical abnormalities, whereas men with structural abnormalities. Overall 5-year MACE-free survival was comparable between both genders. However, when the patients were divided into 3 groups by age [young (<50 years), middle-aged (50-64 years) and elderly (≥65 years)], the survival was significantly lower in the young female group (young 82%, middle-aged 92%, elderly 96%, P<0.01), where a significant interaction was noted between age and smoking. In contrast, the survival was comparable among the 3 age groups of male patients. These results indicate that there are gender differences in the characteristics and outcomes of VSA patients, suggesting the importance of gender-specific management of the disorder. 

  19. Clinical Features of Autoimmune Autonomic Ganglionopathy and the Detection of Subunit-Specific Autoantibodies to the Ganglionic Acetylcholine Receptor in Japanese Patients

    PubMed Central

    Koga, Michiaki; Kanda, Takashi; Murata, Kenya; Suzuki, Takashi; Kurono, Hiroko; Kunimoto, Masanari; Kaida, Ken-ichi; Mukaino, Akihiro; Sakai, Waka; Maeda, Yasuhiro; Matsuo, Hidenori

    2015-01-01

    Autoimmune autonomic ganglionopathy (AAG) is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR) may play a central role. Radioimmunoprecipitation (RIP) assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50) of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG. PMID:25790156

  20. Clinical significance of the "galaxy sign" in patients with pulmonary sarcoidosis in a Japanese single-center cohort.

    PubMed

    Koide, Takashi; Saraya, Takeshi; Tsukahara, Yayoi; Bonella, Francesco; Börner, Eda; Ishida, Manabu; Ogawa, Yukari; Hirukawa, Ichiro; Oda, Miku; Shimoda, Masafumi; Ohkuma, Kosuke; Fujiwara, Masachika; Takata, Saori; Yokoyama, Takuma; Kurai, Daisuke; Ishii, Haruyuki; Goto, Hajime; Takizawa, Hajime

    2016-10-07

    The galaxy sign is an irregularly marginated pulmonary nodule formed by a confluence of multiple small nodules, and it is a diagnostic radiological finding for pulmonary sarcoidosis. However, the clinical significance of the galaxy sign for sarcoidosis has been poorly investigated. This study aimed to investigate the clinical significance and detailed radiological features of the galaxy sign in patients with pulmonary sarcoidosis. We retrospectively reviewed 87 patients with biopsy-proven sarcoidosis and 108 patients with pulmonary tuberculosis. Galaxy sign incidence was assessed on thoracic high-resolution computed tomography (HRCT) images from each group. Correlations of galaxy sign with clinical characteristics and disease outcomes were evaluated for patients with sarcoidosis. HRCT findings were available for 65 of 87 patients with pulmonary sarcoidosis and all 108 patients with pulmonary tuberculosis. Galaxy sign incidence was significantly higher in patients with pulmonary sarcoidosis (n=15, 23.1%) than in those with pulmonary tuberculosis (n=2, 1.9%, p<0.001). Among the 65 patients with pulmonary sarcoidosis, those with galaxy signs (n=15) were significantly younger (median: 32 years, interquartile range [IQR] 28-38 years) than those without (n=50) (median: 62 years, IQR 37.7-73 years). The CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) was also significantly lower in the former group (median: 2.6, IQR 2.0-3.9 vs. median 5.8, IQR 3.7-8.6, p<0.001). Galaxy signs are associated with younger age and low BALF CD4/CD8 ratio but not disease severity.

  1. Similarities and differences among eosinophilic esophagitis, proton-pump inhibitor-responsive esophageal eosinophilia, and reflux esophagitis: comparisons of clinical, endoscopic, and histopathological findings in Japanese patients.

    PubMed

    Jiao, Dijin; Ishimura, Norihisa; Maruyama, Riruke; Ishikawa, Noriyoshi; Nagase, Mamiko; Oshima, Naoki; Aimi, Masahito; Okimoto, Eiko; Mikami, Hironobu; Izumi, Daisuke; Okada, Mayumi; Ishihara, Shunji; Kinoshita, Yoshikazu

    2017-02-01

    Esophageal eosinophilia is classified as either eosinophilic esophagitis (EoE) or proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE), depending on the response to PPI treatment. The aim of this study was to compare the clinical, endoscopic, and histopathological findings of EoE and PPI-REE in Japanese patients. In addition, the characteristics of these cases were compared with those of reflux esophagitis (RE) cases. Eleven patients diagnosed with EoE, 16 with PPI-REE, and 39 with RE, who were all consecutively examined from 2005 to 2015 at Shimane University Hospital, were enrolled. Clinical, endoscopic, and histopathological esophageal findings in these groups were retrospectively examined and compared. The differences in the clinical characteristics of EoE and PPI-REE were not remarkable, though patients with EoE and PPI-REE were younger, presented a higher prevalence of allergic comorbidities, and complained of symptoms of dysphagia more frequently than those with RE. The only noteworthy differences between EoE and PPI-REE were more frequent reports of asthma (36.4 vs. 2.6 %) and food allergy (27.3 vs. 0 %) by patients with EoE (P < 0.05, P < 0.05, respectively). Endoscopic findings in patients with EoE and PPI-REE were similar, with the presence of esophageal erosions in a small percentage of PPI-REE cases being the only difference. There were no histopathological differences between EoE and PPI-REE. Comparisons of clinical, endoscopic, and histopathological findings between EoE and PPI-REE showed that these two types have similar characteristics, though EoE patients showed a higher atopic background. Predicting PPI responsiveness in cases with esophageal eosinophilia is difficult and requires further investigation.

  2. Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.

    PubMed

    Kawai, H; Akaike, M; Kunishige, M; Inui, T; Adachi, K; Kimura, C; Kawajiri, M; Nishida, Y; Endo, I; Kashiwagi, S; Nishino, H; Fujiwara, T; Okuno, S; Roudaut, C; Richard, I; Beckmann, J S; Miyoshi, K; Matsumoto, T

    1998-11-01

    We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

  3. Clinical characteristics and long-term prognosis of vasospastic angina patients who survived out-of-hospital cardiac arrest: multicenter registry study of the Japanese Coronary Spasm Association.

    PubMed

    Takagi, Yusuke; Yasuda, Satoshi; Tsunoda, Ryusuke; Ogata, Yasuhiro; Seki, Atsushi; Sumiyoshi, Tetsuya; Matsui, Motoyuki; Goto, Toshikazu; Tanabe, Yasuhiko; Sueda, Shozo; Sato, Toshiaki; Ogawa, Satoshi; Kubo, Norifumi; Momomura, Shin-ichi; Ogawa, Hisao; Shimokawa, Hiroaki

    2011-06-01

    Coronary artery spasm plays an important role in the pathogenesis of ischemic heart disease; however, its role in sudden cardiac death remains to be fully elucidated. We examined the clinical characteristics and outcomes of patients with vasospastic angina (VSA) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. Between September 2007 and December 2008, 1429 patients with VSA (male/female, 1090/339; median, 66 years) were identified. They were characterized by a high prevalence of smoking and included 35 patients who survived out-of-hospital cardiac arrest (OHCA). The OHCA survivors, as compared with the remaining 1394 non-OHCA patients, were characterized by younger age (median, 58 versus 66 years; P<0.001) and higher incidence of left anterior descending coronary artery spasm (72% versus 53%, P<0.05). In the OHCA survivors, 14 patients underwent implantable cardioverter-defibrillator (ICD) implantation while intensively treated with calcium channel blockers. Survival rate free from major adverse cardiac events was significantly lower in the OHCA survivors compared with the non-OHCA patients (72% versus 92% at 5 years, P<0.001), including appropriate ICD shocks for ventricular fibrillation in 2 patients. Multivariable analysis revealed that OHCA events were significantly correlated with major adverse cardiac events (hazard ratio, 3.25; 95% confidence interval, 1.39 to 7.61; P<0.01). These results from the largest vasospastic angina cohort indicate that vasospasm patients who survived OHCA are high-risk population. Further studies are needed to determine whether implantable cardioverter-defibrillator therapy improves patient prognosis.

  4. Safety and effectiveness of gemcitabine in 260 patients with biliary tract cancer in a Japanese clinical practice based on post-marketing surveillance in Japan.

    PubMed

    Okubo, Sumiko; Nishiuma, Shinichi; Kobayashi, Noriko; Taketsuna, Masanori; Taniai, Hisashi

    2012-11-01

    Gemcitabine was approved for the treatment of biliary tract cancer in 2006 in Japan. While biliary tract cancer is usually associated with patients 70 years of age or older and/or those who tend to have underlying liver dysfunction, data on this population were limited in the Japanese Phase II study of gemcitabine. Thus, further evaluation of safety and effectiveness in this population was planned. This special post-marketing surveillance was conducted as an observational study on the use of gemcitabine in a clinical practice setting. Gemcitabine-naïve patients with biliary tract cancer were enrolled from 2006 to 2008 and observed over 12 months; one or more doses of gemcitabine were administered during the period. Data such as patient background, treatment details, adverse events occurring during the observational period, laboratory values of liver enzyme and survival status were collected 3 and 12 months after the start of therapy. Of the 285 patients registered for the study, 260 were included in the analysis. The mean age was 66.9 years. There were 120 patients (46.2%) classified as elderly (70 years or older). Haematotoxicities were the most common adverse drug reactions. In the elderly and the non-elderly, adverse drug reactions (serious) occurred in 48.3% (20.8%) and 50.7% (12.9%), respectively. The overall estimated 1-year survival rate was 52.5% (95% confidence interval, 45.9-58.7%). In line with previous clinical and post-marketing studies conducted in Japan, the results of this study suggest that gemcitabine could be used safely and effectively for biliary tract cancer patients including the elderly.

  5. Multiregional clinical trials: Japanese perspective on drug development strategy and sample size for Japanese subjects.

    PubMed

    Ando, Yuki; Uyama, Yoshiaki

    2012-09-01

    Multiregional clinical trials including Japanese subjects are playing a key role in new drug development in Japan. In addition to the consideration of differences in intrinsic and extrinsic ethnic factors, deciding the sample size of Japanese subjects is an important issue when a multiregional clinical trial is intended to be used for Japanese submission. Accumulated experience suggests that there are several points to consider, such as the basic principles described in the guidance document, drug development strategy, trial phase, and disease background. The difficulty of interpreting the results of Japanese trials should also be considered.

  6. Multiple system atrophy: clinicopathological characteristics in Japanese patients

    PubMed Central

    OZAWA, Tetsutaro; ONODERA, Osamu

    2017-01-01

    Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that has both clinical and pathological variants. Clinical examples include MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA-P), whereas olivopontocerebellar atrophy and striatonigral degeneration represent pathological variants. We performed systematic reviews of studies that addressed the relative frequencies of clinical or pathological variants of MSA in various populations to determine the clinicopathological characteristics in Japanese MSA. The results revealed that the majority of Japanese patients have MSA-C, while the majority of patients in Europe and North America have MSA-P. A comparative study of MSA pathology showed that the olivopontocerebellar-predominant pathology was more frequent in Japanese MSA than in British MSA. Demonstrated differences in pathological subtype thus appear consistent with differences in the clinical subtype of MSA demonstrated between Japan and European populations. We concluded that olivopontocerebellar-predominant pathology and MSA-C may represent clinicopathological characteristics in Japanese MSA. Factors determining predominant involvement of olivopontocerebellar regions in MSA should therefore be explored. PMID:28496050

  7. Drug use disorders in Japanese eating disorder patients.

    PubMed

    Nagata, Toshihiko; Kawarada, Yojiro; Ohshima, Jun; Iketani, Toshiya; Kiriike, Nobuo

    2002-03-15

    A previous questionnaire study suggested that drug use disorder (DUD: abuse/dependence on drugs, other than alcohol) in Japanese eating disorder (ED) patients was less prevalent than in Western countries, although eating and drug use disorders have spread simultaneously in Western countries. However, the precise prevalence and comorbidity features remain unknown. Subjects consisted of 62 patients with anorexia nervosa restricting type; 48 patients with anorexia nervosa binge eating/purging type; and 75 patients with bulimia nervosa purging type. The Japanese version of the Structured Clinical Interview for DSM-III-R; the Structured Clinical Interview for DSM-III-R Personality Disorders; and the supplement module of the Schedule for Affective Disorders and Schizophrenia-Lifetime version were used for the interview. Sixteen (8.6%, 95% CI = 4.6-12.7%) patients had lifetime diagnoses of DUD. Drugs were solvent fumes or benzodiazepines, and only one patient had been dependent on methamphetamine. More than half of the patients with lifetime DUD diagnoses were multi-impulsivitists. On multivariate analysis, DUD was significantly linked with childhood parental loss, history of conduct disorder and borderline personality disorder. Thus, the prevalence of DUD in Japanese ED patients was indeed lower than that in Western countries. However, similar comorbidity was found in ED patients with DUD compared with that of those in Western countries. The current study suggests that ED and DUD have different origins, although they share the feature of impulsivity. Further study in the general population is needed to clarify these issues.

  8. Clinical outcome of combined immunotherapy with interferon-alpha and low-dose interleukine-2 for Japanese patients with metastatic renal cell carcinoma.

    PubMed

    Miyake, Hideaki; Kurahashi, Toshifumi; Takenaka, Atsushi; Inoue, Taka-aki; Fujisawa, Masato

    2009-01-01

    The objective of this study was to retrospectively investigate clinical outcomes of combined immunotherapy with interferon-alpha (IFN-alpha) and low-dose interleukin-2 (IL-2) in Japanese patients with metastatic renal cell carcinoma (RCC). This study included a total of 52 patients with metastatic RCC who were treated by combined immunotherapy with IFN-alpha and low-dose IL-2 following radical nephrectomy. These patients received a subcutaneous injection of IFN-alpha (5 to 6 million U/d) three times per week and intravenous injection of IL-2 (1.4 million U/d) twice per week. Tumor response was evaluated every 16 weeks, and as a rule, this weekly regimen was repeated 50 times in patients with evidence of objective response or stable disease. In this series, complete response and partial response were achieved in 1 and 11 patients, respectively; however, the remaining 20 and 20 patients were diagnosed as showing stable disease and progressive disease, respectively. Of several parameters examined, presence of metastases at diagnosis and C-reactive protein (CRP) level were significantly associated with response to this combined therapy. The 1-, 3-, and 5-year cancer-specific survival rates of these 52 patients were 80.4%, 51.7%, and 38.8%, respectively. Furthermore, cancer-specific survival was significantly associated with performance status, presence of metastases at diagnosis, metastatic organ and CRP level on univariate analysis; however, only performance status and presence of metastases at diagnosis appeared to be independent predictors of cancer-specific death by multivariate analysis. Toxicities related to this therapy were generally mild and tolerable, limited to World Health Organization (WHO) grade 1 or 2 in the majority of patients. Collectively, these findings suggest that combined immunotherapy with IFN-alpha and low-dose IL-2 could achieve comparatively acceptable oncological outcomes in patients with metastatic RCC; however, other therapeutic options

  9. Distinct Characteristics in Japanese Dermatitis Herpetiformis: A Review of All 91 Japanese Patients over the Last 35 Years

    PubMed Central

    Ohata, Chika; Ishii, Norito; Hamada, Takahiro; Shimomura, Yutaka; Niizeki, Hironori; Dainichi, Teruki; Furumura, Minao; Tsuruta, Daisuke; Hashimoto, Takashi

    2012-01-01

    We reviewed all 91 Japanese dermatitis herpetiformis (DH) patients reported over the last 35 years. The male-to-female ratio was 2 : 1. The mean age at onset was 43.8, and 13 years earlier for female patients. More than half of these Japanese DH patients showed granular IgA deposition in the papillary dermis, and another one-third showed fibrillar IgA deposition. The male patients with granular IgA deposition were 10 years older than those with fibrillar deposition. Whereas patients with granular IgA deposition showed typical distribution of the skin lesions, the predilection sites of DH tended to be spared in patients with fibrillar IgA deposition. Only 3 patients had definite gluten-sensitive enteropathy. There was a statistical difference in the frequency of human leukocyte antigen (HLA)-DR9 between the granular group and controls among Japanese. No patients had HLA-DQ2 or -DQ8, which is frequently found in Caucasian DH patients. The absence of HLA-DQ2/DQ8, the inability to identify celiac disease in most cases, the predominance of fibrillar IgA, and the unusual distribution of clinical lesions in Japanese patients suggest that Japanese DH may be a subset of DH patients and have a pathogenesis which is different from that currently proposed in Caucasian DH patients. PMID:22778765

  10. Clinical efficacy and safety of topiroxostat in Japanese hyperuricemic patients with or without gout: a randomized, double-blinded, controlled phase 2b study.

    PubMed

    Hosoya, Tatsuo; Sasaki, Tomomitsu; Ohashi, Tetsuo

    2017-03-01

    Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used in Japan for the treatment of hyperuricemic patients with or without gout. In terms of the effectiveness of topiroxostat in lowering serum urate levels, the dose-response relationship has been evaluated; however, it remains to be verified. A randomized, multi-center, double-blinded study of topiroxostat was performed for Japanese hyperuricemic patients with or without gout. During the 16-week study, 157 Japanese hyperuricemic patients with or without gout were randomly assigned to receive a placebo, topiroxostat at 120 or 160 mg/day, or allopurinol at 200 mg/day. The primary endpoint of this study was to determine the lowering rate of serum uric acid levels compared to those of baseline at the end of administration. A dose-response relationship (regarding decreases in the serum urate levels) was confirmed for the placebo and topiroxostat at 120 and at 160 mg/day. Moreover, at the end of administration, the lowering rate of serum urate levels was determined to be -44.8% in the topiroxostat 160-mg/day group. No significant difference in the incidence of adverse events was observed among all groups, including the allopurinol group. The serum urate-lowering effect of topiroxostat was found to have a dose-response relationship in Japanese hyperuricemic patients with or without gout.

  11. Relationship between the clinical efficacy and AUC/MIC of intravenous ciprofloxacin in Japanese patients with intraabdominal infections.

    PubMed

    Ohki, Emiko; Yamagishi, Yuka; Mikamo, Hiroshige

    2013-10-01

    The efficacy of fluoroquinolones (FQs) correlates with the pharmacokinetic/pharmacodynamic (PK-PD) parameter, AUC/MIC. To our knowledge, however, no prospective studies have reported the relationship between FQ efficacy and PK-PD parameters in intraabdominal infection; therefore, we prospectively investigated the relationship between the efficacy of intravenous ciprofloxacin (CPFX IV) and PK-PD parameters. The study included 16 patients diagnosed with peritonitis between 2006 and 2008: 14 patients infected with a single organism and 2 patients infected with more than one organism. Each patient was treated with CPFX IV (300 mg twice daily). The response rate was 56% (9 responders and 7 non-responders). Non-responders were infected with Escherichia coli, Pseudomonas aeruginosa, and Bacteroides fragilis (6 patients were infected with a single organism and 1 with more than one organism). Plasma drug concentrations were measured 1 h and 2 or 4 h after administration of CPFX IV. AUC for 24 h (AUC(0-24))/MIC values was calculated. The range of AUC(0-24)/MIC values in responders [95.3-3628.4 (geometric mean, 521.6)] was significantly different from that in non-responders [7.0-45.2 (geometric mean, 16.5)] (p = 0.001). The target AUC/MIC value of CPFX IV would be considered to be 45-95 in patients with peritonitis.

  12. Pooled model-based approach to compare the pharmacokinetics of entecavir between Japanese and non-Japanese chronic hepatitis B patients.

    PubMed

    Yoshitsugu, Hiroyuki; Sakurai, Takao; Ishikawa, Hiroki; Roy, Amit; Bifano, Marc; Pfister, Marc; Seriu, Taku; Hiraoka, Masaki

    2011-05-01

    This study evaluated the population pharmacokinetics (PK) of entecavir in Japanese patients with chronic hepatitis B infection enrolled in 2 Japanese phase IIb clinical trials and compared them to non-Japanese patients enrolled in global phase II trials. The objectives were to identify significant and clinically meaningful covariate effects on entecavir population pharmacokinetic parameters and assess whether differences exist between Japanese and non-Japanese patients. A total of 843 observations were obtained from 142 patients who received once daily administration of entecavir at 0.1, 0.5, and 1.0 mg doses in the 2 Japanese studies. Consistent with findings in non-Japanese patients, creatinine clearance estimated with ideal body weight (ICrCL) was found to be statistically significant for clearance in a 2-compartment model. Also, the entecavir dose was identified as a covariate on intercompartmental clearance. Age, gender, and hepatic function were not identified as covariate for clearance. The estimated population average of oral clearance in a typical patient with a reference ICrCL value of 100 mL/min was 26.4 L/h (interindividual variability: 19.4%). This model-based analysis indicates that the PK of entecavir are similar in Japanese and non-Japanese chronic hepatitis B patients.

  13. Baseline characteristics and interim (3-month) efficacy and safety data from STELLA-LONG TERM, a long-term post-marketing surveillance study of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice.

    PubMed

    Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Nakamura, Ichiro

    2016-10-01

    To evaluate the efficacy and safety of ipragliflozin in real-world clinical practice in Japanese patients with type 2 diabetes. We conducted interim analyses at 3 months of a 3-year prospective study of patients who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015, and whose data were locked by 16 January 2016. Changes in glycemic control, blood pressure, and laboratory variables from baseline, and incidence of adverse drug reactions (ADRs). Of 11,412 patients initially registered, efficacy and safety data were available for 3481 (30.5%) and 4360 (38.2%) patients, respectively. Hemoglobin A1c and fasting plasma glucose decreased by 0.67% and 28.8 mg/dL, respectively, at 3 months/last assessment (both P < .001) from baseline (8.00% and 166.4 mg/dL, respectively). Blood pressure and lipid levels also improved significantly. There were 258 ADRs in 194 patients. The ADRs included 'renal and urinary disorders' (system organ class) in 110 patients (2.5%). These 3-month interim results indicate that ipragliflozin improved glycemic control, lipids, and blood pressure with low rates of ADRs in Japanese patients with type 2 diabetes in real-world clinical practice. The results were consistent with those of placebo-controlled, randomized clinical trials. Clinicaltrials.gov identifier: NCT02479399.

  14. Applying Japanese management tips to patient accounts.

    PubMed

    Groenevelt, C J

    1990-04-01

    "Just in time," a Japanese management philosophy that has been applied successfully in manufacturing operations, also can be used to improve management of patient accounts departments. Under its principles, healthcare organizations would develop standardized procedures; involve workers in decision making; set up training and education programs aimed at creating a multi-skilled pool of workers; establish smooth production schedules; and foster cooperation and commitment to the philosophy throughout the organization.

  15. The FOXL2 mutation (c.402C>G) in adult-type ovarian granulosa cell tumors of three Japanese patients: clinical report and review of the literature.

    PubMed

    Takahashi, Akimasa; Kimura, Fuminori; Yamanaka, Akiyoshi; Takebayashi, Akie; Kita, Nobuyuki; Takahashi, Kentaro; Murakami, Takashi

    2013-12-01

    Adult-type granulosa cell tumor (AGCT) is a rare class of malignant ovarian tumor with unique features, characterized by slow growth, late recurrence, relatively good prognosis and unified cause in almost all patients. The forkhead box L2 (FOXL2) gene encodes an essential transcription factor in the ovary. FOXL2 is important in female sex determination, follicle recruitment, and granulosa cell development. About 70-97% of AGCTs were reported to carry a somatic mutation c.402C>G (C134W) in the FOXL2 gene. However, it is unknown whether AGCTs of Japanese patients harbor the FOXL2 c.402C>G mutation. Here, we report a mutational analysis of the FOXL2 gene in four Japanese patients with AGCTs, and we review the literature to determine the precise incidence of FOXL2 mutations in AGCTs. All four patients were analyzed by immunohistochemistry for FOXL2. Genomic DNA was extracted from paraffin-embedded tissues, and was analyzed to detect the c.402C>G mutation in FOXL2 by direct sequencing. All tumors were stained with FOXL2. Three of the four tumors harbor the c.402C>G mutation. Based on the literature review, FOXL2 immunostaining is a highly specific marker for sex cord-stromal tumors (SCSTs), but it is not specific for AGCTs, one subtype of SCSTs. We identified 340 patients with the FOXL2 mutation (c.402C>G) and determined that the incidence of the mutation is 91.9% in AGCT patients. Therefore, this FOXL2 mutation is specific to AGCTs in the ovary and is useful for diagnosis of this disease.

  16. Efficacy and safety of collagenase Clostridium histolyticum injection for Dupuytren's contracture in non-Caucasian Japanese patients (CORD-J Study): the first clinical trial in a non-Caucasian population.

    PubMed

    Hirata, H; Tanaka, K; Sakai, A; Kakinoki, R; Ikegami, H; Tateishi, N

    2016-06-16

    To assess the efficacy, safety and pharmacokinetics of 0.58 mg collagenase Clostridium histolyticum injections for the treatment of Dupuytren's contracture in Japanese patients, we conducted a phase III, multicentre, uncontrolled, open-label clinical study in patients with Dupuytren's contracture. Of the 77 patients, 66 achieved clinical success in the primary treated joint (86%; 95% confidence interval: 76% to 93%), confirming the efficacy of collagenase Clostridium histolyticum injections. More improvement was seen in the metacarpophalangeal joints than in the proximal interphalangeal joints (94% versus 73%). The main adverse reaction was a local reaction in the injected hand. No tendon rupture or anaphylactic reactions were seen. The concentrations of collagenase Clostridium histolyticum were below the lower limit of quantification in plasma samples at all time points. As seen in global studies in Caucasian patients, a corrective effect on Dupuytren's contracture and good tolerance were observed in most non-Caucasian (Asian) Japanese patients. Level 3. © The Author(s) 2016.

  17. Clinical efficacy, radiographic progression, and safety through 156 weeks of therapy with subcutaneous golimumab in combination with methotrexate in Japanese patients with active rheumatoid arthritis despite prior methotrexate therapy: final results of the randomized GO-FORTH trial

    PubMed Central

    Tanaka, Yoshiya; Harigai, Masayoshi; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Yamamoto, Kazuhiko; Miyasaka, Nobuyuki; Koike, Takao; Baker, Daniel; Ishii, Yutaka; Yoshinari, Toru

    2016-01-01

    Abstract Objective: To evaluate the safety and efficacy of golimumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA). Methods: Japanese patients with active RA despite MTX were randomized to placebo + MTX (Group 1, n = 88), golimumab 50 mg + MTX (Group 2, n = 86), or golimumab 100 mg + MTX (Group 3, n = 87). Patients with <20% improvement in swollen/tender joint counts entered early escape at week 16. At week 24, all remaining placebo patients crossed over to golimumab 50 mg. Efficacy assessments included ACR20, DAS28-ESR, and HAQ-DI. Radiographic progression was assessed with the van der Heijde-modified Sharp (vdH-S) score. Results: ACR20 response rates in Group 1, Group 2, and Group 3 were 67.9, 86.1, and 82.4%, respectively, at week 52 and were maintained through week 104 (87.1, 94.0, and 88.7%) and week 156 (97.1, 94.1, and 89.5%). Proportions of patients with good/moderate DAS28-ESR response or clinically meaningful improvement in HAQ-DI were also maintained through week 156. The majority of patients did not experience radiographic progression through week 156. Among 257 golimumab-treated patients, 251 (97.7%) had ≥1 AE; 54 (21.0%) had ≥1 serious AE through week 156. Infections were the most common type of AE. Conclusions: Response to golimumab + MTX was maintained over 3 years in Japanese patients with active RA despite MTX. Safety results were consistent with the known safety profile of golimumab. PMID:26474192

  18. Clinical characteristics of and risk factors for serious infection in Japanese patients within six months of remission induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis registered in a nationwide, prospective, inception cohort study.

    PubMed

    Watanabe-Imai, Kaori; Harigai, Masayoshi; Sada, Ken-Ei; Yamamura, Masahiro; Fujii, Takao; Dobashi, Hiroaki; Amano, Koichi; Ito, Satoshi; Homma, Sakae; Kumagai, Shunichi; Banno, Shogo; Arimura, Yoshihiro; Makino, Hirofumi

    2017-07-01

    The purpose of this study was to identify the clinical characteristics and predictors of serious infections (SIs) in the RemIT-JAV, a nationwide, prospective, inception cohort study for Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). We analyzed SIs within six months of remission induction therapy in 156 AAV patients. Hazard ratios with 95% confidence intervals (CIs) for SIs were calculated using the COX proportional hazard model. Sixty-three SIs in 42 patients were identified. The incidence rate (IR) of SIs was 87.59/100 patient-years. The median length of time to the onset of first SIs was 54 days. Hazard ratios (95%CI) for SIs were 1.97 (0.99-3.95) for age >65 years, 0.47 (0.25-0.89) for female sex, 2.11 (1.05-4.27) for the severe form of AAV, and 2.88 (1.49-5.88) for initial PSL >0.8 mg/kg/day in the first model, and 2.64 (1.39-5.01) for smoking and 3.27 (1.66-6.45) for initial PSL >0.8 mg/kg/day in the second model. Lowering the IR of SIs in Japanese AAV patients is mandatory to improve the vital prognosis of these patients. For remission induction therapy of AAV patients with these risk factors, risk management of immunosuppressive treatment should be carefully considered.

  19. Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine-refractory differentiated thyroid cancer.

    PubMed

    Kiyota, Naomi; Schlumberger, Martin; Muro, Kei; Ando, Yuichi; Takahashi, Shunji; Kawai, Yasukazu; Wirth, Lori; Robinson, Bruce; Sherman, Steven; Suzuki, Takuya; Fujino, Katsuki; Gupta, Anubha; Hayato, Seiichi; Tahara, Makoto

    2015-12-01

    Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. This subanalysis evaluated the efficacy and safety of lenvatinib in Japanese patients who participated in SELECT. Outcomes for Japanese patients (lenvatinib, n = 30; placebo, n = 10) were assessed in relationship to the SELECT population (lenvatinib, n = 261; placebo, n = 131). The primary endpoint was PFS; secondary endpoints included overall survival, overall response rate, and safety. Lenvatinib PFS benefit was shown in Japanese patients (median PFS: lenvatinib, 16.5 months; placebo, 3.7 months), although significance was not reached, presumably due to sample size (hazard ratio, 0.39; 95% confidence interval, 0.10-1.57; P = 0.067). Overall response rates were 63.3% and 0% for lenvatinib and placebo, respectively. No significant difference was found in overall survival. The lenvatinib safety profile was similar between the Japanese and overall SELECT population, except for higher incidences of hypertension (any grade: Japanese, 87%; overall, 68%; grade ≥3: Japanese, 80%; overall, 42%), palmar-plantar erythrodysesthesia syndrome (any grade: Japanese, 70%; overall, 32%; grade ≥3: Japanese, 3%; overall, 3%), and proteinuria (any grade: Japanese, 63%; overall, 31%; grade ≥3: Japanese, 20%; overall, 10%). Japanese patients had more dose reductions (Japanese, 90%; overall, 67.8%), but fewer discontinuations due to adverse events (Japanese, 3.3%; overall, 14.2%). There was no difference in lenvatinib exposure between the Japanese and overall SELECT populations after adjusting for body weight. In Japanese patients with radioiodine-refractory differentiated thyroid cancer, lenvatinib showed similar clinical outcomes to the overall SELECT population. Some differences in adverse event frequencies and dose

  20. Japanese Society of Clinical Oncology clinical practice guidelines 2010 for antiemesis in oncology: executive summary.

    PubMed

    Takeuchi, Hideki; Saeki, Toshiaki; Aiba, Keisuke; Tamura, Kazuo; Aogi, Kenjiro; Eguchi, Kenji; Okita, Kenji; Kagami, Yoshikazu; Tanaka, Ryuhei; Nakagawa, Kazuhiko; Fujii, Hirofumi; Boku, Narikazu; Wada, Makoto; Akechi, Tatsuo; Udagawa, Yasuhiro; Okawa, Yutaka; Onozawa, Yusuke; Sasaki, Hidenori; Shima, Yasuo; Shimoyama, Naohito; Takeda, Masayuki; Nishidate, Toshihiko; Yamamoto, Akifumi; Ikeda, Tadashi; Hirata, Koichi

    2016-02-01

    The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT3) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT3 receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT3 receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.

  1. Efficacy and safety of empagliflozin in Japanese patients with type 2 diabetes mellitus: A sub-analysis by body mass index and age of pooled data from three clinical trials.

    PubMed

    Shiba, Teruo; Ishii, So; Okamura, Tomoo; Mitsuyoshi, Rika; Pfarr, Egon; Koiwai, Kazuki

    2017-09-01

    To investigate the efficacy and safety of empagliflozin in subgroups based on body mass index (BMI) and age, using a pooled data set from Japanese patients with type 2 diabetes mellitus (T2DM). Pooled data from 1403 patients treated with empagliflozin at 10mg/day or 25mg/day in three clinical studies (≥52week treatment) were stratified by baseline BMI (<22, 22 to <25 and ≥25kg/m(2)) and baseline age (<50, 50 to <65 and ≥65years). Empagliflozin at 10mg/day and 25mg/day reduced mean glycated hemoglobin (HbA1c) (-0.77 to -0.87% and -0.76 to -0.97%, respectively), mean fasting plasma glucose (FPG) (-20.79 to -27.06mg/dL and -26.08 to -29.60mg/dL) and mean body weight (-3.4 to -4.7% and -3.7 to -4.7%) in all subgroups of baseline BMI and age, regardless of age and degree of obesity. Adverse events were observed in approximately 70-80% patients in BMI and age subgroups of both empagliflozin groups. No hypoglycemia requiring assistance was observed. Neither UTI nor genital infection rates differed markedly among the BMI and age subgroups. Volume depletion was increased in patients ≥65years of age as compared to younger patients. Empagliflozin was well tolerated and improved HbA1c, FPG and body weight in all BMI and age subgroups of Japanese patients with T2DM, regardless of age and degree of obesity. Empagliflozin is considered to be effective and well tolerated for treating a wide range of Japanese patients with T2DM. Study 1 (NCT01193218), Study 2 (NCT01289990) and Study 3 (NCT01368081). Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Bevacizumab safety in Japanese patients with colorectal cancer.

    PubMed

    Hatake, Kiyohiko; Doi, Toshihiko; Uetake, Hiroyuki; Takahashi, Yoichiro; Ishihara, Yumi; Shirao, Kuniaki

    2016-03-01

    Bevacizumab (Avastin(®)) was approved in Japan in April 2007 for patients with advanced or metastatic colorectal cancer. To address the limited clinical experience in Japanese patients, a post-approval surveillance study was undertaken in bevacizumab-treated patients in Japan. Bevacizumab (5 or 10 mg/kg every 2 weeks) was administered with chemotherapy; patients were observed for 26 weeks from initiation of treatment. The primary objective was to investigate the incidence of adverse drug reactions, particularly those of interest for bevacizumab. Univariate and multivariate analyses were performed to identify potential risk factors for adverse drug reactions. In total, 2712 patients were registered and 2696 patients were included in the safety analysis. Hypertension (13.1%), hemorrhage (10.5%) and proteinuria (4.5%) were the most common adverse drug reaction. The incidences of serious adverse drug reactions were low: gastrointestinal perforation occurred in 0.9% of patients, hemorrhage in 1.3%, arterial thromboembolic events in 0.3%, venous thromboembolic events in 1.3% and wound-healing complications in 0.4%. The incidence of bevacizumab-specific adverse drug reactions was not influenced by the bevacizumab dose. Multivariate analyses identified risk factors for the following adverse drug reactions: hypertension (prior/concurrent hypertension); tumor-associated bleeding (performance status, prior/concomitant anticoagulant or nonsteroidal anti-inflammatory drug use); proteinuria (sex, performance status, prior/concurrent diabetes and proteinuria); gastrointestinal perforation (primary tumor in situ, concurrent nonsteroidal anti-inflammatory drug use); venous thromboembolic event (treatment stage, port insertion). The safety profile of bevacizumab-containing regimens in this Japanese population was comparable with studies performed in Western countries. Bevacizumab is generally well tolerated in Japanese patients with advanced or metastatic colorectal cancer. © The

  3. Computer-aided diagnosis system for bone scintigrams from Japanese patients: importance of training database.

    PubMed

    Horikoshi, Hiroyuki; Kikuchi, Akihiro; Onoguchi, Masahisa; Sjöstrand, Karl; Edenbrandt, Lars

    2012-10-01

    Computer-aided diagnosis (CAD) software for bone scintigrams have recently been introduced as a clinical quality assurance tool. The purpose of this study was to compare the diagnostic accuracy of two CAD systems, one based on a European and one on a Japanese training database, in a group of bone scans from Japanese patients. The two CAD software are trained to interpret bone scans using training databases consisting of bone scans with the desired interpretation, metastatic disease or not. One software was trained using 795 bone scans from European patients and the other with 904 bone scans from Japanese patients. The two CAD softwares were evaluated using the same group of 257 Japanese patients, who underwent bone scintigraphy because of suspected metastases of malignant tumors in 2009. The final diagnostic results made by clinicians were used as gold standard. The Japanese CAD software showed a higher specificity and accuracy compared to the European CAD software [81 vs. 57 % (p < 0.05) and 82 vs. 61 % (p < 0.05), respectively]. The sensitivity was 90 % for the Japanese CAD software and 83 % for the European CAD software (n.s). The CAD software trained with a Japanese database showed significantly higher performance than the corresponding CAD software trained with a European database for the analysis of bone scans from Japanese patients. These results could at least partly be caused by the physical differences between Japanese and European patients resulting in less influence of attenuation in Japanese patients and possible different judgement of count intensities of hot spots.

  4. Clinical and angiographic evaluation of the resolute zotarolimus-eluting coronary stent in Japanese patients – long-term outcome in the RESOLUTE Japan and RESOLUTE Japan small vessel study.

    PubMed

    Saito, Shigeru; Maehara, Akiko; Vlachojannis, Georgios J; Parise, Helen; Mehran, Roxana

    2015-01-01

    This study evaluated the safety and efficacy of the RESOLUTE(TM)zotarolimus-eluting stent (R-ZES; Medtronic, Inc, Santa Rosa, CA, USA) in Japanese patients for the treatment of de novo native coronary lesions. Both RESOLUTE Japan (R-Japan) and RESOLUTE Japan Small Vessel Study (R-Japan SVS) were prospective, multicenter, single-arm observational studies. R-Japan enrolled 100 patients (reference vessel diameter, 2.5-3.5 mm) and R-Japan SVS enrolled 65 patients (at least 1 lesion suitable for 2.25-mm stent) treated with R-ZES. In R-Japan, in-stent late lumen loss (LLL; the primary endpoint) at 8 months was 0.12 ± 0.22 mm and volume obstruction on intravascular ultrasound was 2.33 ± 3.51%. At 4 years, there were no cases of clinically driven target lesion revascularization (TLR); the target lesion failure (TLF; composite of cardiac death, target vessel myocardial infarction, and clinically driven TLR) was 5.6% (5/90). In R-Japan SVS, in-stent LLL at 9 months was 0.27 ± 0.33 mm, TLF (primary endpoint) was 4.6% (3/65), without incidence of TLR. At 3 years, TLF was 7.9% (5/63) and clinically driven TLR, 3.2% (2/63). R-Japan and R-Japan SVS demonstrate substantial suppression of neointimal hyperplasia, low LLL, and excellent and sustained long-term clinical outcome with R-ZES in Japanese patients.

  5. Validation of the Japanese disease severity classification and the GAP model in Japanese patients with idiopathic pulmonary fibrosis.

    PubMed

    Kondoh, Shun; Chiba, Hirofumi; Nishikiori, Hirotaka; Umeda, Yasuaki; Kuronuma, Koji; Otsuka, Mitsuo; Yamada, Gen; Ohnishi, Hirofumi; Mori, Mitsuru; Kondoh, Yasuhiro; Taniguchi, Hiroyuki; Homma, Sakae; Takahashi, Hiroki

    2016-09-01

    The clinical course of idiopathic pulmonary fibrosis (IPF) shows great inter-individual differences. It is important to standardize the severity classification to accurately evaluate each patient׳s prognosis. In Japan, an original severity classification (the Japanese disease severity classification, JSC) is used. In the United States, the new multidimensional index and staging system (the GAP model) has been proposed. The objective of this study was to evaluate the model performance for the prediction of mortality risk of the JSC and GAP models using a large cohort of Japanese patients with IPF. This is a retrospective cohort study including 326 patients with IPF in the Hokkaido prefecture from 2003 to 2007. We obtained the survival curves of each stage of the GAP and JSC models to perform a comparison. In the GAP model, the prognostic value for mortality risk of Japanese patients was also evaluated. In the JSC, patient prognoses were roughly divided into two groups, mild cases (Stages I and II) and severe cases (Stages III and IV). In the GAP model, there was no significant difference in survival between Stages II and III, and the mortality rates in the patients classified into the GAP Stages I and II were underestimated. It is difficult to predict accurate prognosis of IPF using the JSC and the GAP models. A re-examination of the variables from the two models is required, as well as an evaluation of the prognostic value to revise the severity classification for Japanese patients with IPF. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  6. Pathophysiology and Japanese clinical characteristics in Marfan syndrome.

    PubMed

    Fujita, Daishi; Takeda, Norifumi; Imai, Yasushi; Inuzuka, Ryo; Komuro, Issei; Hirata, Yasunobu

    2014-08-01

    Marfan syndrome is an autosomal dominant heritable disorder of the connective tissue, caused by mutations of the gene FBN1, which encodes fibrillin-1, a major component of the microfibrils of the extracellular matrix. Fibrillin-1 interacts with transforming growth factor-β (TGF-β), and dysregulated TGF-β signaling plays a major role in the development of connective tissue disease and familial aortic aneurysm and dissection, including Marfan syndrome. Losartan, an angiotensin II blocker, has the potential to reduce TGF-β signaling and is expected to be an additional therapeutic option. Clinical diagnosis is made using the Ghent nosology, which requires comprehensive patient assessment and has been proven to work well, but evaluation of some of the diagnostic criteria by a single physician is difficult and time-consuming. A Marfan clinic was established at the University of Tokyo Hospital in 2005, together with cardiologists, cardiac surgeons, pediatricians, orthopedists, and ophthalmologists in one place, for the purpose of speedy and accurate evaluation and diagnosis of Marfan syndrome. In this review, we discuss the recent progress in diagnosis and treatment of Marfan syndrome, and the characteristics of Japanese patients with Marfan syndrome.

  7. Long-term safety and seizure outcome in Japanese patients with Lennox-Gastaut syndrome receiving adjunctive rufinamide therapy: An open-label study following a randomized clinical trial.

    PubMed

    Ohtsuka, Yoko; Yoshinaga, Harumi; Shirasaka, Yukiyoshi; Takayama, Rumiko; Takano, Hiroki; Iyoda, Kuniaki

    2016-03-01

    To evaluate the long-term safety and seizure outcome in Japanese patients with Lennox-Gastaut syndrome (LGS) receiving adjunctive rufinamide therapy. We conducted an open-label extension study following a 12-week multicenter, randomized, double-blind, placebo-controlled study of adjunctive rufinamide therapy in Japanese patients with LGS. Fifty-four patients participated in the extension study. Seizure frequency was evaluated until 52 weeks after the start of the extension study. Adverse events (AEs) were evaluated throughout both studies. Of the 54 patients, 41 (75.9%) completed the extension study. The median duration of exposure to rufinamide was 818.0 days in all 54 patients, and 38 patients (70.4%) received rufinamide for 2 years or more. The median percent change in the frequency of tonic-atonic seizures relative to the frequency at the start of the double-blind study was -39.3% (12 weeks), -40.6% (24 weeks), -46.8% (32 weeks), -47.6% (40 weeks), and -36.1% (52 weeks). Reduction of total seizure frequency was also maintained until 52 weeks. Frequent treatment-related AEs were somnolence (20.4%), decreased appetite (16.7%), transient seizure aggravation including status epilepticus (13.0%), vomiting (11.1%), and constipation (11.1%). Adverse events were mild or moderate, except for transient seizure aggravation in three patients. Adverse events resulting in discontinuation of rufinamide were decreased appetite, drug eruption, and worsening of underlying autism. When clinically notable weight loss was defined as a decrease ≥ 7% relative to baseline, 22 patients (40.7%) experienced weight loss at least once during long-term observation, although weight loss was reported as an AE in only three patients. This study demonstrated a long-term benefit of rufinamide as adjunctive therapy for Japanese patients with LGS. Exacerbation of seizures and decreased appetite/weight loss should be monitored carefully. Copyright © 2016 The Authors. Published by Elsevier B

  8. Clinical efficacy and safety of topiroxostat in Japanese male hyperuricemic patients with or without gout: an exploratory, phase 2a, multicentre, randomized, double-blind, placebo-controlled study.

    PubMed

    Hosoya, T; Sasaki, T; Hashimoto, H; Sakamoto, R; Ohashi, T

    2016-06-01

    In Japan, although topiroxostat, a selective xanthine oxidoreductase inhibitor, has been used for the treatment of patients with hyperuricemia including gout, no published randomized controlled studies evaluating the dose-dependent relationship with respect to the serum urate-lowering efficacy have been reported. The aim of this study was to evaluate the dose-dependent relationship with serum urate-lowering efficacy and safety of topiroxostat in Japanese hyperuricemic patients including gout. We conducted an exploratory, phase 2a, multicentre, randomized, double-blind, 8-week, placebo-controlled study in Japanese hyperuricemic patients with or without gout. The study arms were placebo and topiroxostat 40, 60, 80 or 120 mg/day. The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit. One hundred and eighty-seven eligible patients were randomized and 186 received at least one dose of the study drug. The study results demonstrated a dose-dependent serum urate reduction effect ranging from 40 to 120 mg/day (P < 0·001, Jonckheere-Terpstra test). The mean per cent change in serum urate level from baseline at the final visit was -30·8% in the 120-mg group and 1·6% with placebo, with a between-group difference of -32·4% ([95% confidence interval, -38·9% to -25·9%]; P < 0·001). Incidences of overall adverse events (AEs) in the topiroxostat groups were comparable to those in the placebo group; however, the incidence of AEs in the 120-mg group was statistically lower than that in the placebo group. The incidences of gouty arthritis were not statistically but numerically higher in the topiroxostat 80- and 120-mg groups. A dose-dependent serum urate-lowering efficacy of topiroxostat was observed in Japanese hyperuricemic male patients with or without gout. Further clinical studies aimed at evaluating the long-term safety and clinical efficacy are warranted. © 2016 The Authors. Journal of Clinical Pharmacy and

  9. A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors.

    PubMed

    Shimizu, Toshio; Fukuoka, Kazuya; Takeda, Masayuki; Iwasa, Tutomu; Yoshida, Takeshi; Horobin, Joanna; Keegan, Mitchell; Vaickus, Lou; Chavan, Ajit; Padval, Mahesh; Nakagawa, Kazuhiko

    2016-05-01

    VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2. This phase 1 study evaluated the safety and tolerability, pharmacokinetics, and clinical activity of VS-6063 in Japanese subjects with advanced solid tumor malignancies in a first-in-Asian study setting. VS-6063 was administered orally twice daily (b.i.d.) in 21-day cycles to cohorts of three subjects each with a standard 3 + 3 dose-escalation design until disease progression or unacceptable toxicity. Blood samples for pharmacokinetics were collected on Day 1 and 15. The assessments were performed using CTCAE v4.0 for adverse events (AEs), and the Response Evaluation Criteria In Solid Tumors, version v1.1 (RECIST v1.1) for tumor response. Nine patients were treated across three dose levels (200-600 mg BID). No dose-limiting toxicities were observed at any dose level. Most frequent treatment-related AEs were Grade 1/2 unconjugated hyperbilirubinemia, fatigue, decreased appetite, and diarrhea. Only one subject in the 200 mg BID cohort experienced reversible and transient Grade 3 unconjugated hyperbilirubinemia. PK analyses confirmed that the exposure at the recommended Phase 2 dose (RP2D) of 400 mg BID was comparable with exposures previously reported in non-Japanese subjects. Durable stable disease of approximately 24 weeks was confirmed in two subjects (malignant mesothelioma and rectal cancer). VS-6063 was well tolerated at all dose levels investigated in this first-in-Asian study. These data support the administration of VS-6063 to Japanese subjects at the RP2D in clinical trials involving solid tumor malignancies.

  10. Risk factors for coronary artery calcification in Japanese patients.

    PubMed

    Shikada, Tomoki; Washio, Masakazu; Nishizaki, Akiko; Kakino, Takamori; Ooe, Kensuke; Ishibashi, Yuuji; Sagara, Shuuichirou; Morishige, Kunio; Tashiro, Hideki

    2015-07-01

    Because the prevalence of coronary artery calcification is lower among Japanese than among Western individuals, aspects of the Japanese lifestyle might be related to the development of calcification. We aimed to clarify the relationship between coronary artery calcium scores in Japanese patients and various lifestyle factors among the Japanese population. Study subjects were patients aged ≥20 years who underwent multidetector-row computed tomography. A total of 201 patients agreed to take part in this study and answered a questionnaire regarding lifestyle, medical history, and other factors. Old age, current and former smoking, sedentary work, short sleep time, coronary artery stenosis, treatment with statins, medical history of cerebrovascular disease, medical history of angina pectoris, medical history of ischemic heart disease, and medical history of dyslipidemia were associated with higher odds ratios than the other factors examined, while the Japanese-style breakfast (e.g. boiled rice, miso soup, grilled fish) was associated with lower odds ratios. In this study, smoking, sedentary work, short sleep time, and the Japanese-style breakfast were lifestyle factors related to coronary artery calcification. The lifestyle of Japanese people may be related to coronary calcification. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  11. Validation of a Japanese version of the Scoliosis Research Society-22 Patient Questionnaire among idiopathic scoliosis patients in Japan.

    PubMed

    Hashimoto, Hideki; Sase, Takeshi; Arai, Yasuhisa; Maruyama, Toru; Isobe, Keijirou; Shouno, Yasuhiro

    2007-02-15

    A cross-sectional observational study to determine the response distribution, internal consistency, and construct, concurrent, and discriminative validities of The Scoliosis Research Society-22 (SRS-22) Patient Questionnaire translated into Japanese as compared with the other language versions. To validate the Japanese version of SRS22. The SRS-22 was translated into several languages but yet not into Japanese. The Japanese SRS-22 and Medical Outcomes Study Short Form 36 were simultaneously administered to 114 adolescent idiopathic scoliosis patients. Exploratory factor analysis revealed a 4-factor structure, though several items were not loaded as theoretically expected. The originally constructed Japanese SRS-22 subscales and the English version showed similar response distribution. Internal consistency was fair but lower than that of the English version. The concurrent validity of the translated version, except for the self-image subscale, was supported using Medical Outcomes Study Short Form 36 subscales as a reference. The function scale differed significantly by curve angle magnitude and treatment status. The self-image score was the highest in patients under observation when curve angle was < 40 degrees, while postsurgical patients marked the highest scores when the angle > or = 40 degrees, respectively. The Japanese SRS-22 is valid and may be useful for clinical evaluation of Japanese scoliosis patients, though the self-image subscale may need further assessment.

  12. Factors Affecting Professional Autonomy of Japanese Nurses Caring for Culturally and Linguistically Diverse Patients in a Hospital Setting in Japan.

    PubMed

    Kuwano, Noriko; Fukuda, Hiromi; Murashima, Sachiyo

    2016-11-01

    The study aimed to analyze the professional autonomy of Japanese nurses when caring for non-Japanese patients and to identify its contributing factors. A descriptive cross-sectional design was used. Participants included 238 clinical nurses working at 27 hospitals in Japan. The Intercultural Sensitivity Scale (Chen and Starosta), and the Scale for Professional Autonomy in Nursing (Kikuchi and Harada) were used to measure intercultural sensitivity and professional autonomy. Stepwise multiple regression analysis was used to identify the most significant factors affecting professional autonomy. Professional autonomy of Japanese nurses caring for non-Japanese patients was significantly lower than when caring for Japanese patients (142.84 vs. 172.85; p < .001). Contributing factors were intercultural sensitivity (p < .001), length of nurse experience (p < .05), and availability of interpretation service (p < .05). Incorporating transcultural nursing content into training programs in schools and hospitals could enhance professional autonomy of Japanese nurses by promoting intercultural sensitivity. © The Author(s) 2015.

  13. Efficacy and safety of topical JTE-052, a Janus kinase inhibitor, in Japanese adult patients with moderate-to-severe atopic dermatitis: A phase 2, multi-centre, randomised, vehicle-controlled clinical study.

    PubMed

    Nakagawa, H; Nemoto, O; Igarashi, A; Nagata, T

    2017-09-28

    JTE-052 is a novel Janus kinase inhibitor presently under clinical development for the topical treatment of atopic dermatitis (AD). To evaluate the efficacy and safety of JTE-052 ointment in Japanese adult patients with AD. Methods Patients with moderate-to-severe AD were randomised (2:2:2:2:1:1) to receive JTE-052 ointment at 0.25%, 0.5%, 1% or 3%, the vehicle ointment or 0.1% tacrolimus ointment (reference) twice daily for 4 weeks. The primary efficacy endpoint was the percent change in modified Eczema Area Severity Index (m-EASI) score from the baseline at the end of treatment (EOT). Secondary efficacy endpoints included change from baseline in the pruritus numeric rating scale (NRS) score. A total of 327 patients were enrolled. At EOT, the least-squares mean percent change from baseline in m-EASI score for JTE-052 0.25%, 0.5%, 1%, 3% and the vehicle ointment was -41.7%, -57.1%, -54.9%, -72.9% and -12.2%, respectively. All JTE-052 groups showed significant reductions of m-EASI score versus the vehicle group (p <0.001 for all). In the tacrolimus group, the mean percent change in m-EASI score was -62.0%. JTE-052 groups also showed significant improvement in other parameters; notably, the pruritus NRS score was reduced as early as Day 1 night-time. JTE-052 ointment at doses up to 3% was safe and well tolerated. Topical JTE-052 markedly and rapidly improved clinical signs and symptoms in Japanese adult patients with moderate-to-severe AD with a favourable safety profile. The study results indicate that topical JTE-052 is a promising therapeutic option for AD. This article is protected by copyright. All rights reserved. JAPICCTI-152887. This article is protected by copyright. All rights reserved.

  14. Application of modeling and simulation to a long-term clinical trial: a direct comparison of simulated data and data actually observed in Japanese osteoporosis patients following 3-year ibandronate treatment.

    PubMed

    Nakai, Kiyohiko; Iida, Satofumi; Tobinai, Masato; Hashimoto, Junko; Kawanishi, Takehiko

    2015-03-01

    Ibandronate, a nitrogen-containing bisphosphonate, is a bone resorption inhibitor widely used to prevent and treat osteoporosis. To optimize the design for a long-term clinical study of ibandronate, modeling and simulation (M&S) was performed based on the result of population pharmacodynamic analysis using the data of a short-term clinical study. A population pharmacodynamic model was constructed by the urinary C-terminal telopeptide of type I collagen (uCTx) and the lumbar spine bone mineral density (BMD) data obtained in clinical studies, including a phase II study of Japanese osteoporosis patients treated with ibandronate for 6 months. Changes in BMD over a period of 3 years were simulated from the population pharmacodynamic parameters of the patients in this phase II study. The relationship between uCTx and BMD was well described by this modeling. The functions of disease progression and supplemental treatment were incorporated into the model to simulate a long-term clinical study with high accuracy. A long-term clinical study with a 3-year treatment was conducted after this M&S. The percentage change from baseline in observed BMD values were found to be similar to the prospectively simulated values. This study showed that M&S could be a useful and powerful tool for designing and conducting long-term clinical studies when carried out in the following sequence: (1) conduct a short-term clinical study; (2) perform M&S; and (3) conduct the long-term clinical study. Application of this procedure to various other treatment agents will establish the usefulness of M&S for long-term clinical studies and bring further efficiencies to drug development.

  15. Correlation between pharmacokinetic/pharmacodynamic indices and clinical outcomes in Japanese patients with skin and soft tissue infections treated with daptomycin: analysis of a phase III study.

    PubMed

    Takesue, Yoshio; Mikamo, Hiroshige; Kusachi, Shinya; Watanabe, Shinichi; Takahashi, Kenichi; Yoshinari, Tomoko; Ishii, Mikio; Aikawa, Naoki

    2015-09-01

    The relationships between pharmacokinetic (PK)/pharmacodynamic (PD) indices and outcomes were investigated in patients with skin and soft tissue infection (SSTI) who received daptomycin at 4 mg/kg/day. Efficacy was evaluated in 55 patients from whom Staphylococcus aureus was isolated, with success rates of 94.5% and 69.1% for clinical and microbiological responses, respectively. The odds ratio for the relationship between the area under the day 1 concentration-time curve (AUC0-24h) to the MIC and the probability of clinical success was 1.03 (95% confidence interval [CI] 0.73-1.45), and that for the relationship for probability of microbiological success was 0.94 (95% CI 0.81-1.09). In 82 patients in the safety analysis, only 1 met the creatine phosphokinase (CPK) elevation criteria, and this patient's minimum concentration (C(min)) of plasma daptomycin was 5.37 μg/mL. No significant relationship was found between peak CPK and C(min) (Pearson's correlation coefficient -0.0452). In conclusion, no clear correlation between PK/PD indices and the probability of efficacy or safety events was demonstrated when daptomycin was administered in SSTI patients using the clinically recommended dosage of 4 mg/kg/day.

  16. Mutational analysis of adrenoleukodystrophy (ALD) gene in Japanese ALD patients

    SciTech Connect

    Koike, R.; Onodera, O.; Tabe, H.

    1994-09-01

    Recently a putative ALD gene containing a striking homology with peroxisomal membrane protein (PMP70) has been identified. Besides childhood ALD, various clinical phenotypes have been identified with the onset in adolescence or adulthood (adrenomyeloneuropathy (AMN), adult cerebral ALD or cerebello-brainstem dominant type). The different clinical phenotypes occasionally coexist even in the same family. To investigate if there is a correlation between the clinical phenotypes and genotypes of the mutations in the ALD gene, we have analyzed 43 Japanese ALD patients. By Southern blot analysis, we identified non-overlapping deletions of 0.5 kb to 10.4 kb involving the ALD gene in 3 patients with adult onset cerebello-brainstem dominant type. By detailed direct sequence analysis, we found 4 patients who had point mutations in the coding region. An AMN patient had a point mutation leading to {sup 266}Gly{r_arrow}Arg change, and another patient with adult cerebral ALD had a 3 bp deletion resulting in the loss of glutamic acid at codon 291, which is a conserved amino acid both in ALD protein and PMP70. Two patients with childhood ALD had point mutations leading to {sup 507}Gly{r_arrow}Val, and {sup 518}Arg{r_arrow}Gln, respectively. Since amino acids from 507 to 520 are highly conserved as ATP-binding cassette transporter proteins, mutations in this region are expected to result in dramatic changes of the function of this protein. Although there is a tendancy for mutation in childhood ALD to be present within the ATP-binding site motif, we found two adult patients who had large deletions involving the region. Taken together, strong correlation between genotypes and clinical phenotypes is unlikely to exist, and some other modifying factors might well play an important role for the clinical manifestations of ALD.

  17. [The newly certified 105 Japanese medical technologists in clinical microbiology].

    PubMed

    Kumasaka, Kazunari

    2002-05-01

    Interest in quality assurance(QA) in clinical laboratories in Japan has increased over the past 30 years. We have however been lagging behind countries such as the USA, Canada and the UK in QA of clinical microbiology. The main problem of QA in Japan is human resources. There are only about 400 laboratory physicians certified by the Japanese Society of Laboratory Medicine(JSLM). Almost no academics in microbiology are interested in QA and they mostly lack clinical competence. There is a small number of faculty positions, and promotions are mostly based on research productivity while medical graduates are increasingly drawn to bench work for basic, short-term research. The Japanese Society for Clinical Microbiology (JSCM) was established in 1990 in order to promote the development of clinical microbiology and its relevant fields in Japan. And 2001 was a milestone in sustained efforts of the JSLM to initiate qualifying examinations of medical technologists(MT) in clinical microbiology. 105 MT in clinical microbiology were newly certified by the Joint Committee of JSCM, JSLM, Japanese Association of Medical Technologists (JAMT) and College of Clinical Pathology of Japan(CCPJ). The certified MTs have appropriate educational background and are well motivated. With good on-the-job training, they are expected to perform effectively various tasks, including laboratory management. Recent radical changes in the health care delivery system have also had serious implications on laboratory services and QA of microbiological tests. The primary goal of the clinical microbiology laboratory is to provide accurate diagnostic testing and high-quality service at a low cost for its customers. It is believed that the Joint Committee and the newly certified MTs will contribute to narrowing the gap between Japan and other countries in clinical microbiology.

  18. Disclosure of true diagnosis in Japanese cancer patients.

    PubMed

    Hosaka, T; Awazu, H; Fukunishi, I; Okuyama, T; Wogan, J

    1999-01-01

    Full disclosure of medical diagnosis to cancer patients in Japan remains controversial. Some physicians in Japan believe that full disclosure may affect the outcome of treatment, create stress and psychiatric problems, or lead to suicide. Although the trend toward full disclosure is increasing in Japan, approximately 70% of current cancer patients are still not fully informed of their condition. In this study, the authors examined the psychiatric status and effects of full disclosure among 100 otolaryngology patients at Tokai University Hospital (50 with benign diseases, 50 with malignancy) using major depression and adjustment disorders criteria of the DSM-III-R Structured Clinical Interview (SCID). This demonstrated that 15 of 50 (30%) patients with benign diseases and 23 of 50 (46%) patients with malignant diseases met the criteria for depression and adjustment disorder; 29 of the 50 patients (58%) with malignant cancer were not informed of their true condition, according to the wishes of their families (21 were fully informed). The prevalence rate of psychiatric disorders was 42.9% among the informed group and 48.3% among the uninformed group. These findings suggest that concealing the true diagnosis was not related to the presence of psychiatric disorders in Japanese cancer patients.

  19. Age-dependent eradication of Helicobacter pylori in Japanese patients

    PubMed Central

    Mamori, Satoshi; Higashida, Akihiro; Kawara, Fumiaki; Ohnishi, Katsuhiro; Takeda, Akihiko; Senda, Eri; Ashida, Cho; Yamada, Hajime

    2010-01-01

    AIM: To determine the general risk factors affecting the failure rate of first-line eradication therapy in Japanese patients with Helicobacter pylori (H. pylori) infection. METHODS: The present study enrolled 253 patients who had an H. pylori infection, underwent gastro-endoscopy, and were treated with H. pylori eradication therapy. Eradication therapy consisted of 30 mg lansoprazole plus 750 mg amoxicillin and 400 mg clarithromycin twice daily for 7 d. All of the patients underwent a 13C urea breath test at least 1 mo after the completion of eradication therapy. The current study investigated the independent factors associated with successful H. pylori eradication using a multiple logistic regression analysis. RESULTS: The overall success rate in the patients was 85.8%. Among the general factors examined in the multivariate analyses, only having an age less than 50 years was found to be significantly associated with a poor response to H. pylori eradication. Moreover, side effects were the only clinical factors in the patients who were under 50 years of age that significantly influenced the poor response to H. pylori eradication. CONCLUSION: H. pylori-positive elderly patients should undergo eradication therapy. In addition, it is necessary to improve H. pylori eradication therapy in younger patients. PMID:20806435

  20. Tuberculous spondylitis in elderly Japanese patients.

    PubMed

    Maeda, Yuki; Izawa, Kazutaka; Nabeshima, Takaharu; Yonenobu, Kazuo

    2008-01-01

    Although the number of patients with tuberculous spondylitis in Japan is increasing slowly, the proportion of the elderly among these patients is increasing more quickly. The purpose of this study was to describe the clinical features and diagnostic imaging findings in elderly tuberculous spondylitis patients in order to enhance diagnosis of the condition in the elderly population. We conducted a retrospective review of 23 patients over 70 years of age previously diagnosed with tuberculous spondylitis. Clinical signs and symptoms, including local pain, fever, and neurological deficits, were analyzed. Routine laboratory tests, including the erythrocyte sedimentation rate, the white blood cell count, and the C-reactive protein level were also reviewed. The results of plain X-rays and magnetic resonance imaging were studied. Patients' signs and symptoms were as follows: local pain in 19 patients (83%); fever in 7 patients (30%) and no fever in 16 patients (70%); and neurological deficits in 13 patients (57%). C-Reactive protein was less than 1.0 mg/dl in 6 patients (26%). Radiography revealed several changes in the affected vertebrae; 3 patients had atypical changes involving only a single vertebra. It is difficult to diagnose tuberculous spondylitis in the elderly because there are atypical symptoms, a scarcity of inflammatory changes, and degenerative changes normally seen in the elderly may mask the radiographic changes due to tuberculous spondylitis. Tuberculous spondylitis should be considered a possibility in the differential diagnosis of back pain in the elderly, especially in countries with a significant history of tuberculosis in the population.

  1. Comparison of baseline characteristics and clinical course in Japanese patients with type 2 diabetes among whom different types of oral hypoglycemic agents were chosen by diabetes specialists as initial monotherapy (JDDM 42)

    PubMed Central

    Fujihara, Kazuya; Igarashi, Risa; Matsunaga, Satoshi; Matsubayashi, Yasuhiro; Yamada, Takaho; Yokoyama, Hiroki; Tanaka, Shiro; Shimano, Hitoshi; Maegawa, Hiroshi; Yamazaki, Katsuya; Kawai, Koichi; Sone, Hirohito

    2017-01-01

    Abstract Little is known about the relationships between patient factors and the antihyperglycemic agents that have been prescribed as initial therapy by diabetes specialists for patients with type 2 diabetes. Moreover, there has been little clarification of the subsequent usage patterns and related factors that influenced the continuation or discontinuation of the drug or the addition of another drug. To provide information on these issues, we evaluated the clinical characteristics of Japanese patients with type 2 diabetes for whom different types of oral hypoglycemic agents (i.e., either sulfonylureas, biguanides, or DPP-4 inhibitors (DPP-4Is)) were chosen as initial monotherapy by diabetes specialists and evaluated subsequent usage patterns. Prescription data on 3 different antidiabetic agents from December 2009 to March 2015 from diabetes specialists’ patient registries were used to identify variables at baseline related to initial prescriptions; also, the addition of another hypoglycemic drug or discontinuation of the initial therapy was evaluated 1 year after the initial prescription. Analyzed were data on 2666 patients who received initial monotherapy with either a sulfonylurea (305 patients), biguanide (951 patients), or DPP-4I (1410 patients). Patients administered sulfonylureas were older, had a lower body mass index (BMI), longer duration of diabetes, and worse glycemic control than recipients of biguanides. Use of biguanides was related to younger age, short duration of diabetes, and obesity but was negatively associated with poor glycemic control. Older age but neither obesity nor poor glycemic control was associated with DPP-4Is. In all 3 groups a high HbA1c value was related to adding another hypoglycemic agent to the initial therapy. Moreover, adding another drug to a DPP-4I was related to a younger age and higher BMI. Patients’ age, duration of diabetes, obesity, and glycemic control at baseline influenced the choice of hypoglycemic agents

  2. Efficacy of keishibukuryogan, a traditional Japanese herbal medicine, in treating cold sensation and numbness after stroke: clinical improvement and skin temperature normalization in 22 stroke patients.

    PubMed

    Fujita, Keishi; Yamamoto, Tetsuya; Kamezaki, Takao; Matsumura, Akira

    2010-01-01

    Cold sensation and numbness have been reported as post-stroke sensory sequelae attributable to distal axonopathy, which is caused by chronic ischemia of diseased limbs resulting from dysfunction of vasomotor regulatory systems. Keishibukuryogan is a traditional herbal medicine used to treat symptoms of peripheral ischemia such as cold extremities. This study investigated clinical improvement and skin temperature in peripheral ischemia patients to determine the efficacy of keishibukuryogan in alleviating post-stroke cold sensation and numbness. Twenty-two stroke patients with cold sensation and/or numbness were enrolled in this study. Subjective cold sensation and numbness, evaluated using the visual analogue scale, were found in 21 and 31 limbs, respectively. The skin temperature of diseased and healthy limbs was recorded. We observed all patients for 4 weeks and 17 patients for 8 weeks after administration of keishibukuryogan. The skin temperature of diseased limbs was significantly higher than baseline at 4 weeks and 8 weeks, whereas that of healthy limbs did not change significantly. Cold sensation and numbness were significantly improved at 4 weeks and 8 weeks compared to baseline. Keishibukuryogan administration resulted in warming of diseased limbs and improved cold sensation and numbness, probably by increasing peripheral blood flow.

  3. Japanese clinical practice guidelines for congenital biliary dilatation.

    PubMed

    Ishibashi, Hiroki; Shimada, Mitsuo; Kamisawa, Terumi; Fujii, Hideki; Hamada, Yoshinori; Kubota, Masayuki; Urushihara, Naoto; Endo, Itaru; Nio, Masaki; Taguchi, Tomoaki; Ando, Hisami

    2017-01-01

    Until now, there have been no practical clinical guidelines for congenital biliary dilatation (CBD). In this review article, the Japanese Study Group on Congenital Biliary Dilatation (JSCBD) propose to establish clinical practice guidelines for CBD. Because the evidence-based literature is relatively small, we decided to create guidelines based on the consensus of experts, using the medical literature for reference. A total of 20 clinical questions (CQs) were considered by the members of the editorial committee responsible for the guidelines. The CQs included the distinct aspects of CBD: (1) Concepts and Pathology (three CQs); (2) Diagnosis (six CQs); (3) Pancreaticobiliary Complications (three CQs); Treatments and Prognosis (eight CQs). Each statements and comments for CQs were made by the guidelines committee members. CQs were finally approved after review by members of the editorial committee and the guidelines evaluation board of CBD. These guidelines were created to provide assistance in the clinical practice of CBD management; their contents focus on clinical utility, and they include general information on CBD to make this disease more widely recognized. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  4. [Willingness to pay and quality of life in patients with Japanese-cedar pollinosis].

    PubMed

    Kakutani, Chieko; Ogino, Satoshi; Irifune, Morihiro; Takeda, Mariko; Baba, Kenji

    2003-01-01

    Seasonal allergic rhinitis (SAR) is one of the world's most common health problems because it's a high-cost, high-prevalence disease. In this study, we investigated patients' willingness to pay (WTP) for prevention and cure from most common SAR, Japanese-cedar pollinosis. Two hundred and forty patients with Japanese-cedar pollinosis, who visited 4 clinics in Osaka and were measured QOL by the SF-36 Questionnaire (Japanese version) during pollen season, were mailed WTP questionnaire in off-season in 1998. Completed questionnaires were sent back by 175 patients. Most patients (83.5%) were willing to pay less than 10,000 yen. Patients with longer duration of disease or severer nasal symptom tended to be more willing to pay. In contrast, no association was found between WTP and sex, age, occupation and comorbid condition. There were significant impairments in five of eight QOL dimensions in patients of Much-WTP in comparison with Less-WTP. Patients with mild symptom had significant higher medication cost than those with less mild symptom. We conclude that effective treatment, even if it costs much, can satisfy patients and may help to reduce indirect costs as well as to lessen the impact of Japanese-cedar pollinosis on QOL for both patient and society.

  5. Mutation analysis of MUTYH in Japanese colorectal adenomatous polyposis patients.

    PubMed

    Taki, Keiko; Sato, Yuri; Nomura, Sachio; Ashihara, Yuumi; Kita, Mizuho; Tajima, Ikufumi; Sugano, Kokichi; Arai, Masami

    2016-04-01

    Germline MUTYH mutations were investigated in 14 Japanese colorectal polyposis patients without germ line adenomatous polyposis coli (APC) gene mutations. Three patients had a heterozygous IVS10-2A>G MUTYH mutation. The onset of MUTYH-associated polyposis (MAP) occurs later than that of familial adenomatous polyposis with germline APC mutation. Thus, we compared the carrier frequency of MUTYH IVS10-2A>G heterozygote in the APC mutation negative cases with that in 115 controls over 70 years of age who showed no apparent clinical manifestations of cancer and claimed that they had no history of cancer at the time of enrollment. The frequency of IVS10-2A>G heterozygote in APC germline mutation negative polyposis patients was significantly higher than control subject (p = 0.012, Chi square test). Although the sample size is still too small to conclude, the IVS10-2A>G MUTYH heterozygote might add to the risk of developing germline APC mutation negative polyposis.

  6. Factors influencing the survival period in Japanese patients with sporadic Creutzfeldt-Jakob disease.

    PubMed

    Iwasaki, Yasushi; Akagi, Akio; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari

    2015-10-15

    Although Japanese cases of sporadic Creutzfeldt-Jakob disease (sCJD) generally involve longer survival periods compared to those from other countries, details regarding the factors influencing survival are unclear. To determine the influence of certain factors on survival, we retrospectively assessed 51 Japanese MM1-type sCJD patients with respect to background, clinical course, and disease management. No significant differences were found between men and women, tracheotomy and nontracheotomy patients, or patients treated in public and other types of hospitals. Although the survival period of tube-fed patients was significantly longer than that of patients who were not tube fed, survival of patients fed via a nasal tube did not differ significantly from that of gastrostomy-fed patients. The proportion of tube-fed patients was 68.6% (35/51). Disease duration was not significantly associated with age or year of onset. However, it was associated with time from onset to first recognition of myoclonus, first recognition of periodic sharp-wave complexes on electroencephalogram, and progression to the akinetic mutism state. Mechanical ventilation was not performed for any patient. Because the total disease duration increased in cases with a slowly progressive clinical course as a natural outcome, we concluded that the most crucial factor contributing to the prolonged survival of Japanese sCJD patients was tube feeding once the akinetic mutism state had been reached.

  7. Psychological problems for non-Japanese speaking patients in Japan.

    PubMed

    Koyama, Atsuko; Niki, Minoru; Matsuoka, Hiromichi; Sakamoto, Ryo; Sakai, Kiyohiro; Jinnai, Rikako; Yasuda, Kanae

    2012-01-01

    The psychological problems of non-Japanese people are becoming more outstanding, in accordance with the increase of foreign nationals in Japan. Five illustrative cases of English-speaking patients were analyzed, from the viewpoint of psychosomatic medicine. The most common psychiatric disorders were adjustment disorders, because of the cultural differences and language barriers. © 2012 International Society of Travel Medicine.

  8. CLINICAL FEATURES OF TREATED AND UNTREATED TYPE 1 IDIOPATHIC MACULAR TELANGIECTASIA WITHOUT THE OCCURRENCE OF SECONDARY CHOROIDAL NEOVASCULARIZATION FOLLOWED FOR 2 YEARS IN JAPANESE PATIENTS.

    PubMed

    Osaka, Rie; Shiragami, Chieko; Ono, Aoi; Kobayashi, Mamoru; Takasago, Yukari; Yamashita, Ayana; Tsujikawa, Akitaka

    2017-05-24

    To evaluate the clinical features of Type 1 idiopathic macular telangiectasia (IMT) followed up for 2 years. Forty-nine patients with unilateral Type 1 IMT were examined. Thirty-one IMT eyes were treated with direct laser photocoagulation and/or intravitreal bevacizumab; the remaining 18 eyes, with good vision or slight macular edema, were untreated. Changes in best-corrected visual acuity and central retinal thickness between baseline and 24 months after the initial visit were examined. Of 49 eyes, nine were treated with direct laser photocoagulation, 12 with laser photocoagulation and intravitreal bevacizumab, 10 with intravitreal bevacizumab monotherapy, whereas 18 did not receive any treatment. The mean logarithm of the minimum angle of resolution best-corrected visual acuity was 0.20 ± 0.19 (median, 20/29) and 0.13 ± 0.22 (median, 20/25) at baseline and 24 months, respectively (P = 0.023). The mean central retinal thickness was 375.0 ± 94.5 μm and 315.3 ± 78.5 μm at baseline and 24 months, respectively (P < 0.001). Retinal vein occlusion and retinal macroaneurysm occurred in six eyes and one eye, respectively, during follow-up. Treatment with laser photocoagulation and/or intravitreal bevacizumab may be effective for Type 1 IMT, 36.7% of IMT eyes required no treatment over a 2-year follow-up, and other retinal vascular events were not uncommon.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  9. Clinicopathological study of Japanese patients with genetic iron overload syndromes.

    PubMed

    Hattori, Ai; Miyajima, Hiroaki; Tomosugi, Naohisa; Tatsumi, Yasuaki; Hayashi, Hisao; Wakusawa, Shinya

    2012-09-01

    In addition to hemochromatosis, aceruloplasminemia and ferroportin disease may be complicated by iron-induced multiple organ damage. Therefore, clinicopathological features should be evaluated in a wider range of genetic iron disorders. This study included 16 Japanese patients with genetic iron overload syndromes. The responsible genes were CP in four, HAMP in one, HJV in three, TFR2 in five, and SLC40A1 in three patients. No phenotype dissociation was observed in patients with the CP, TFR2, or HAMP genotypes. Two of the three patients with the HJV genotype displayed classic hemochromatosis instead of the juvenile type. Patients with the SLC40A1 genotype were affected by mild iron overload (ferroportin A) or severe iron overload (ferroportin B). Transferrin saturation was unusually low in aceruloplasminemia patients. All patients, except those with ferroportin disease, displayed low serum hepcidin-25 levels. Liver pathology showed phenotype-specific changes; isolated parenchymal iron loading in aceruloplasminemia, periportal fibrosis associated with heavy iron overload in both parenchymal and Kupffer cells of ferroportin B, and parenchyma-dominant iron-loading cirrhosis in hemochromatosis. In contrast, diabetes occurred in all phenotypes of aceruloplasminemia, hemochromatosis, and ferroportin disease B. In conclusion, clinicopathological features were partially characterized in Japanese patients with genetic iron overload syndromes. © 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

  10. Upper gastrointestinal tumours in Japanese familial adenomatous polyposis patients

    PubMed Central

    Yamaguchi, Tatsuro; Ishida, Hideyuki; Ueno, Hideki; Kobayashi, Hirotoshi; Hinoi, Takao; Inoue, Yasuhiro; Ishida, Fumio; Kanemitsu, Yukihide; Konishi, Tsuyoshi; Tomita, Naohiro; Matsubara, Nagahide; Watanabe, Toshiaki; Sugihara, Kenichi

    2016-01-01

    Objective The upper gastrointestinal characteristics in Japanese familial adenomatous polyposis patients have not yet been clarified. The aim of the present study was to elucidate these characteristics in Japanese familial adenomatous polyposis patients. Methods This study was conducted by the study group for familial adenomatous polyposis in the Japanese Society for Cancer of the Colon and Rectum. Familial adenomatous polyposis patients who underwent surgical resection from 2000 to 2012 were included in the study. Results In total, 303 familial adenomatous polyposis patients were enrolled, with 265 cases of classical familial adenomatous polyposis (≥100 adenomas) and 38 cases of attenuated familial adenomatous polyposis (<100 adenomas). Fundic gland polyps were significantly more common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis; however, gastric cancer was significantly less common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis. Gastric cancer and duodenal adenoma were significantly more common in familial adenomatous polyposis patients with gastric adenoma than in those without gastric adenoma. Duodenal cancer was detected in 7 of 72 familial adenomatous polyposis patients with duodenal adenoma. The median tumour risk in 50-year-old familial adenomatous polyposis patients was 55.3, 21.8, 3.8, 39.2 and 7.7% for fundic gland polyp, gastric adenoma, gastric cancer, duodenal adenoma and duodenal cancer, respectively. Conclusions Upper gastrointestinal tumours/polyps were frequently found in familial adenomatous polyposis patients, and their incidences were correlated; however, the frequency of gastric cancer in Japanese familial adenomatous polyposis patients was similar to that in the general population. PMID:26819281

  11. Upper gastrointestinal tumours in Japanese familial adenomatous polyposis patients.

    PubMed

    Yamaguchi, Tatsuro; Ishida, Hideyuki; Ueno, Hideki; Kobayashi, Hirotoshi; Hinoi, Takao; Inoue, Yasuhiro; Ishida, Fumio; Kanemitsu, Yukihide; Konishi, Tsuyoshi; Tomita, Naohiro; Matsubara, Nagahide; Watanabe, Toshiaki; Sugihara, Kenichi

    2016-04-01

    The upper gastrointestinal characteristics in Japanese familial adenomatous polyposis patients have not yet been clarified. The aim of the present study was to elucidate these characteristics in Japanese familial adenomatous polyposis patients. This study was conducted by the study group for familial adenomatous polyposis in the Japanese Society for Cancer of the Colon and Rectum. Familial adenomatous polyposis patients who underwent surgical resection from 2000 to 2012 were included in the study. In total, 303 familial adenomatous polyposis patients were enrolled, with 265 cases of classical familial adenomatous polyposis (≥100 adenomas) and 38 cases of attenuated familial adenomatous polyposis (<100 adenomas). Fundic gland polyps were significantly more common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis; however, gastric cancer was significantly less common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis. Gastric cancer and duodenal adenoma were significantly more common in familial adenomatous polyposis patients with gastric adenoma than in those without gastric adenoma. Duodenal cancer was detected in 7 of 72 familial adenomatous polyposis patients with duodenal adenoma. The median tumour risk in 50-year-old familial adenomatous polyposis patients was 55.3, 21.8, 3.8, 39.2 and 7.7% for fundic gland polyp, gastric adenoma, gastric cancer, duodenal adenoma and duodenal cancer, respectively. Upper gastrointestinal tumours/polyps were frequently found in familial adenomatous polyposis patients, and their incidences were correlated; however, the frequency of gastric cancer in Japanese familial adenomatous polyposis patients was similar to that in the general population. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Dysexecutive syndrome in schizophrenia: A cross-cultural comparison between Japanese and British patients.

    PubMed

    Ihara, H.; Berrios, G.E.; McKenna, P.J.

    2000-01-01

    This study tested the hypothesis that the dysexecutive syndrome of schizophrenia is impervious to cultural differences. 18 Japanese and 22 British patients and 14 Japanese and 19 British control subjects were compared on the BADS (Behavioural Assessment of Dysexecutive Syndrome), a comprehensive neuropsychological assessment battery, designed for 'ecological validity', and other measures of frontal executive functions (EFs). Both cultural groups of schizophrenic patients showed equally severe impairment in most executive tests including the BADS (verbal fluency and intelligence were less impaired). Irrespective of cultural origin, similar neuropsychological deficits were found in patients with minimal intellectual deterioration. Our study suggests that socio-cultural background does not affect the dysexecutive profile of schizophrenia very much, and that neuropsychological assessment may possibly provide added clinical information relevant to the management and rehabilitation of schizophrenic patients across different cultures.

  13. The Vidian Canal: Radiological Features in Japanese Population and Clinical Implications

    PubMed Central

    MATO, David; YOKOTA, Hajime; HIRONO, Seiichiro; MARTINO, Juan; SAEKI, Naokatsu

    2015-01-01

    The vidian canal (VC), a bony tunnel in which the vidian artery and nerve pass, has been widely known as an important landmark to identify the anterior genu of the petrous carotid artery (AGPCA) especially during lateral extended endoscopic endonasal approachs (LEEEAs). The objectives of this study in the Japanese population are to describe the radiological anatomic features and relationships between VC and its surrounding structures, and discuss the clinical implications. We studied 231 high-resolution computed tomography (CT) scans with a slice thickness of 0.5 mm. All the patients had known sellar or parasellar pathologies but without any involvement of VC. The following VC-related parameters were examined: its length, relationship to AGPCA, course from the pterygopalatine fossa to the carotid canal, its position relative to the medial pterygoid plate and pneumatization pattern of the sphenoid sinus. Mean length of VC is 14.6 mm. There is more tendency of straight-running VC compared to other populations. VC locates infero-lateral to AGPCA in all the cases. The protrusion of VC and the paraclival carotid artery to the sphenoid sinus, as well as well-pneumatization of the sinus is also observed more frequently in almost a half of the population. Surgeons who perform LEEEAs in Japanese patients must know these anatomical features. The characteristics particular to Japanese populations may facilitate better identification of VC and exposure to AGPCA intraoperatively. PMID:25744352

  14. Intraocular pressure in Japanese diabetic patients

    PubMed Central

    Matsuoka, Masato; Ogata, Nahoko; Matsuyama, Kayako; Yoshikawa, Tadanobu; Takahashi, Kanji

    2012-01-01

    Background To determine whether the intraocular pressure (IOP) in diabetic patients is significantly different from that in nondiabetic patients. Methods The medical records of all patients who were initially examined in the Department of Ophthalmology, Kansai Medical University, Takii Hospital were reviewed. At the initial examination, patients had a detailed interview and underwent a comprehensive ophthalmic examinations. All patients were over 20 years of age and did not have glaucoma. Results A total of 703 patients were evaluated. The mean (±standard error) IOP of the diabetic patients was 15.5 ± 0.2 mmHg (n = 206), and was significantly higher than the 14.0 ± 0.1 mmHg (n = 497) in the nondiabetic patients (P < 0.0001). The IOP was negatively correlated with age (r = −0.202; P = 0.024) in the diabetic patients and was weakly but significantly correlated with the glycosylated hemoglobin (HbA1c) level (r = 0.240; P = 0.015) in the group with diabetic retinopathy. Conclusion The significantly higher IOP in diabetic patients and positive correlation of IOP with HbA1c levels in patients with diabetic retinopathy indicate that IOP in diabetic patients is higher, especially in those with poor control of diabetes. PMID:22815643

  15. Mortality 6 years after inpatient treatment of female Japanese patients with eating disorders associated with alcoholism.

    PubMed

    Suzuki, Kenji; Takeda, Aya; Yoshino, Aihide

    2011-06-01

    This study was conducted to clarify the mortality of patients with eating disorders associated with alcoholism. We focused on the mortality rate 6 years after inpatient treatment of patients with eating disorders associated with alcoholism compared with eating disorder patients without alcoholism and alcoholic patients without eating disorders. The subjects were 164 female Japanese patients 30 years of age or younger with eating disorders or alcoholism who were inpatients at some time during the period from 1990 to 1998 at the Japanese National Hospital Organization, Kurihama Alcoholism Center. A semi-structured interview concerning alcohol problems, eating problems, psychiatric disorders and other clinical characteristics was conducted at the time of the first admission. A survey concerning survival was conducted in October 2001, and 100% of the patients were followed up. The mortality of the 47 eating disorder patients with alcoholism, 86 eating disorder patients without alcoholism, and 31 alcoholics without eating disorders was 27.7%, 3.5%, and 19.4%, respectively, at 6 years after inpatient treatment, showing significant differences. On the Kaplan-Meier survival curves, the mortality of the eating disorder patients with alcoholism was significantly higher than that of the patients without alcoholism, but not significantly higher than that of young female alcoholics without eating disorders. The 13 eating disorder patients with alcoholism who had died were five anorexia nervosa and seven bulimia nervosa patients. The results of the study suggest that comorbid alcoholism is a major factor in the death of anorexia nervosa and bulimia nervosa patients. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

  16. [Clinical effects of Lactobacillus acidophilus strain L-55-contained yogurt on symptoms of Japanese cedar pollen allergy].

    PubMed

    Kimura, Goro; Akagi, Hirofumi; Okada, Chiharu; Hirano, Atsushi; Amano, Yoshimi; Ohmura, Etsuko; Nakashige, Yoshito; Sunada, Yosuke; Fujii, Yusuke; Nakamura, Syoji; Soda, Ryo; Takahashi, Kiyoshi

    2012-05-01

    It has been reported that oral administration of Lactobacillus acidophilus strain L-55 (L-55) suppressed nasal symptom and antigen-specific IgE induced by antigen challenge in mice. We investigated clinical effects of L-55-contained yogurt on symptoms and IgE production in the patients with Japanese cedar pollinosis. The study was performed as a randomized double blind placebo-controlled trial. L-55-contained yogurt (L-55 yogurt) or placebo yogurt was started to administer to each subject from 4 weeks prior to the onset of Japanese cedar pollen release for total 13 weeks. The mean value of symptom score and symptom medication score were lower in L-55 yogurt group compared with placebo yogurt group during 5th week to 9th week from the first week of Japanese cedar pollination. Especially, in medicated subjects, total symptom score and throat symptom score were significantly lower in L-55 yogurt group compared with placebo yogurt group at 5th and 4th week from the first week of Japanese cedar pollination, respectively. Moreover, in medicated subjects, change ratio of serum total IgE was significantly lower in L-55 yogurt group compared with placebo yogurt group at 1st week from the first week of Japanese cedar pollination. Intake of L-55 during Japanese cedar pollinating season may be effective in alleviating the allergic symptoms related to Japanese cedar pollinosis. From these finding, it was suggested that L-55 is a possible candidate as a complementary medicine for Japanese cedar pollinosis.

  17. Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I-II essential hypertension: a randomized, double-blind clinical study.

    PubMed

    Rakugi, Hiromi; Enya, Kazuaki; Sugiura, Kenkichi; Ikeda, Yoshinori

    2012-05-01

    Azilsartan is a novel angiotensin receptor blocker being developed for hypertension treatment. This 16-week, multicenter, randomized, double-blind study compared the efficacy and safety of azilsartan (20-40 mg once daily by forced titration) and its ability to provide 24-h blood pressure (BP) control, with that of candesartan cilexetil (candesartan; 8-12 mg once daily by forced titration) in 622 Japanese patients with grade I-II essential hypertension. Efficacy was evaluated by clinic-measured sitting BP, and by ambulatory BP monitoring (ABPM) at week 14. Participants (mean age: 57 years, 61% males) had a mean baseline sitting BP of 159.8/100.4 mm Hg. The mean change from baseline in sitting diastolic BP at week 16 (primary endpoint) was -12.4 mm Hg in the azilsartan group and -9.8 mm Hg in the candesartan group, demonstrating a statistically significant greater reduction with azilsartan vs. candesartan (difference: -2.6 mm Hg, 95% confidence interval (CI): -4.08 to -1.22 mm Hg, P=0.0003). The week 16 (secondary endpoint) mean change from baseline in sitting systolic BP was -21.8 mm Hg and -17.5 mm Hg, respectively, a significant decrease with azilsartan vs. candesartan (difference: -4.4 mm Hg, 95% CI: -6.53 to -2.20 mm Hg, P<0.0001). On ABPM, the week 14 mean changes from baseline in diastolic and systolic BP were also significantly greater with azilsartan over a 24-h period, and during the daytime, night-time and early morning. Safety and tolerability were similar among the two groups. These data demonstrate that once-daily azilsartan provides a more potent 24-h sustained antihypertensive effect than that of candesartan but with equivalent safety.

  18. Current status of quality in Japanese clinical trials.

    PubMed

    Saito, Kazuyuki; Kodama, Yasuo; Ono, Shunsuke; Mutoh, Mizue; Kawashima, Susumu; Fujimura, Akio

    2005-08-01

    The changes in the quality of Japanese clinical trials were evaluated by comparing the results of Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (fiscal year (FY) 1997-1999) with those from April 2001 to March 2002 (FY2001). During both of the periods inspections were undertaken by the Organization for Pharmaceutical Safety and Research (OPSR). The audit findings in the former period were based on the audits that covered 331 hospitals and 775 trials conducted under the old GCP guideline. The audits in the latter period targeted 147 hospitals and 238 trials conducted under the old or new GCP guideline. The total number of deficiencies detected by GCP audits in the former three-year period (FY 1997-1999) was 1529, and the corresponding number in the latter single year (FY 2001) was 912. Two remarkable changes in OPSR's findings were observed between FY 1997-1999 and FY 2001 as follows; the proportion of protocol deviations increased from 14.7% (225/1529) to 53.1% (484/912), while the proportion of errors in case report forms (CRFs) decreased from 43.6% (666/1529) to 15.4% (140/912). The new GCP guideline sets very high standards for a hospital's qualification: to have sufficient equipment and hospital resources, to have capacity for promptly responding to urgent trial-related problems, to have an IRB, and to have appropriate staff including clinical research coordinators (CRCs) assigned to the clinical trial. Our results suggest that the impact of the regulatory changes of applicable standard is large for a hospital's qualification for conducting clinical trials in Japan.

  19. Clinical presentation and outcome of avoidant/restrictive food intake disorder in a Japanese sample.

    PubMed

    Nakai, Yoshikatsu; Nin, Kazuko; Noma, Shun'ichi; Hamagaki, Seiji; Takagi, Ryuro; Teramukai, Satoshi; Wonderlich, Stephen A

    2017-01-01

    We conducted a study of the clinical presentation and outcome in patients with avoidant/restrictive food intake disorder (ARFID), aged 15-40years, and compared this group to an anorexia nervosa (AN) group in a Japanese sample. A retrospective chart review was completed on 245 patients with feeding and eating disorders (FEDs), analyzing prevalence, clinical presentation, psychopathological properties, and outcomes. Using the DSM-5 criteria, 27 (11.0%) out of the 245 patients with a FED met the criteria for ARFID at entry. All patients with ARFID were women. In terms of eating disorder symptoms, all patients with ARFID had restrictive eating related to emotional problems and/or gastrointestinal symptoms. However, none of the ARFID patients reported food avoidance related to sensory characteristics or functional dysphagia. Additionally, none of them exhibited binge eating or purging behaviors, and none of them reported excessive exercise. The ARFID group had a significantly shorter duration of illness, lower rates of admission history, and less severe psychopathology than the AN group. The ARFID group reported significantly better outcome results than the AN group. These results suggest that patients with ARFID in this study were clinically distinct from those with AN and somewhat different from pediatric patients with ARFID in previous studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Problem-solving therapy for psychological distress in Japanese early-stage breast cancer patients.

    PubMed

    Hirai, Kei; Motooka, Hiroko; Ito, Naoshi; Wada, Naoko; Yoshizaki, Arika; Shiozaki, Mariko; Momino, Kanae; Okuyama, Toru; Akechi, Tatsuo

    2012-12-01

    The current report provides the result of a Phase II clinical trial regarding the effectiveness and feasibility of problem-solving therapy for psychological distress experienced by Japanese early-stage breast cancer patients. Participants were 36 post-surgery Japanese breast cancer patients in a university hospital located in Osaka Prefecture, Japan. After screening for psychological distress using the Distress and Impact Thermometer and the Hospital Anxiety and Depression Scale, highly distressed patients were exposed to 5 weekly sessions of the problem-solving therapy program. Nineteen patients completed the intervention and follow-up. There was a significant difference between the pre-intervention and the 3-month follow-up in the total Hospital Anxiety and Depression Scale score (P = 0.02), and the mean change score from the pre-intervention to the follow-up was 6.05 (SD = 1.94). The intervention had a large effect size (d = 0.82). There were also significant changes in worry, self-efficacy and quality of life measures. The findings of our study suggest that the problem-solving therapy program has potential to be effective for alleviating psychological distress experienced by Japanese early-stage breast cancer patients. The true effectiveness of the program should be confirmed by a future randomized control trial.

  1. Profiles associated with treatment retention in Japanese patients with methamphetamine use disorder: preliminary survey.

    PubMed

    Kobayashi, Ohji; Matsumoto, Toshihiko; Otsuki, Masaki; Endo, Keiko; Okudaira, Kenichi; Wada, Kiyoshi; Hirayasu, Yoshio

    2008-10-01

    To identify profiles associated with treatment retention in Japanese patients with methamphetamine use disorder. The study used a retrospective design based on clinical records. The subjects were 101 patients at the Kanagawa Psychiatric Center, Serigaya Hospital, who were diagnosed as having methamphetamine use disorder. They were divided in two groups, namely those who remained in treatment 3 months after the initial assessment, and those who did not. The primary analysis compared patient profiles between the two groups to detect discriminating variables, which were then submitted for secondary analysis using logistic regression to determine the most relevant predictor of retention. Primary analysis indicated that older age, having psychotic symptoms, receiving public assistance, and history of incarceration were associated with treatment retention after 3 months. Secondary analysis showed that positive history of incarceration was the most significant predictor of the outcome. History of incarceration had the most significant treatment-retention effect on Japanese patients with methamphetamine use disorder. The development and introduction of integrated programs that link methamphetamine-dependent offenders to drug treatment is recommended in outpatient treatment for Japanese patients with methamphetamine user disorder.

  2. Correlation between SNP genotypes and periodontitis in Japanese type II diabetic patients: a preliminary study.

    PubMed

    Damrongrungruang, Teerasak; Ogawa, Hiroshi; Hori-Matsumoto, Sayaka; Minagawa, Kumiko; Hanyu, Osamu; Sone, Hirohito; Miyazaki, Hideo

    2015-05-01

    The present study aims to investigate the correlation between SNP genotype patterns and periodontitis severity in Japanese type II diabetic patients. A cross-sectional study in 43 Japanese diabetic patients with periodontitis was performed. Blood samples were drawn for single nucleotide polymorphism (SNP) analyses and periodontal index (probing pocket depth and clinical attachment level) was subsequently recorded. Twelve functional genes with SNPs that had been shown to be associated with diabetes and/or inflammation were genotyped using a nuclease-mediated SNP-specific ligation method. Subjects with two or more sites with clinical attachment level ≥6 mm and who additionally had one or more sites with pocket depth ≥5 mm were classified as having severe periodontitis. Proportions of risk genotypes/non-risk genotypes between severe and non-severe periodontitis were subsequently compared. A high frequency (21/43 participants, 49%) of adiponectin gene polymorphism (ADIPOQ 45T > G) homozygous risk genotype (TT genotype) was observed in the participants. The frequency of TGF-β1 SNP (29C > T) risk genotype (TT genotype) in severe periodontitis (34%, n = 11) was significantly higher than in non-severe periodontitis (0%, n = 0) (p = 0.04). Our study suggests that TGF-β1 SNPs (29C > T) may be used as one of the risk indicators for severe periodontitis in Japanese diabetic patients.

  3. Reliability of Japanese clinical trials estimated from GCP audit findings.

    PubMed

    Saito, K; Kodama, Y; Ono, S; Maida, C; Fujimura, A; Miyamoto, E

    2008-08-01

    To describe the reliability of Japanese clinical trials, we compared the results of a Good Clinical Practice (GCP) audit conducted between April 1997 and March 2000 (fiscal year (FY) 1997 - 1999) with those from April 2004 - March 2005 (FY2004). The number and proportion of various types of deficiencies described in GCP audit reports were compared between the 2 periods. The audit findings in the former period were based on official audits that covered 331 hospitals and 775 trials. The audits in the latter period targeted 114 hospitals and 189 trials. The inspection of former period was undertaken by the Organization for Pharmaceuticals Safety and Research (OPSR). On the other hand, the latter period was undertaken by the Pharmaceuticals and Medical Devices Agency (PMDA). The total number of deficiencies detected in GCP audits was 1,529 in the former 3-year period (FY1997 - 1999) and 819 in the latter period (FY2004). The total number of deficiencies detected and reported was more than 1.5-fold on an annual basis in the latter period. By category of deficiencies, the proportion of protocol deviations increased from 14.7 (225/1,529) to 45.7% (374/819), while the proportion of errors in case report forms (CRFs) decreased from 43.6 (666/ 1,529) to 27.1% (222/819). There were two remarkable changes in audit findings between FY1997 - 1999 and FY2004; the increase in the proportion of protocol deviations and the decrease in the proportion of CRF-related deficiencies. We think that in Japan the improvement of research environments is needed to provide reliable clinical data responsible for the regulatory standard of GCP.

  4. Comprehensive analysis of clinical development and regulatory submission promotion schemes for oncologic drugs as the Japanese national projects.

    PubMed

    Nagai, Sumimasa; Ozawa, Keiya

    2016-12-01

    To reduce the delay in marketing authorization of drugs in Japan, four Japanese national projects were instituted. We examined all oncologic drugs for adult patients approved or discussed through these schemes, for the first time. All the data are publicly available. In total, 197 applications/demands (181 indications and 16 dosages/uses) were collected. As of December 31, 2015, 64 indications and 10 dosages/uses were approved as off-label drugs through these schemes without conducting additional registration trials in Japan. Furthermore, 46 indications and two dosages/uses were approved after registration trials in Japan requested by the national scheme councils. Regarding the following 23 indications of the 197 applications/demands, registration trials in Japan were commenced after the national scheme council's request: 17 hematological malignancies and six orphan solid tumors. Moreover, 54 indications and three dosages/uses, for which demands were submitted, were regarded as not a high medical priority by the national scheme council. Regarding two hematological malignancy indications, the dosage approved in foreign countries was intolerable for the Japanese patients in Japanese registration trials and this stopped the clinical development in Japan. Our analysis showed that 110 indications and 12 dosages/uses were approved in Japan through these schemes. These national projects have provided numerous therapeutic options for Japanese patients and may be meaningful for promoting clinical development and regulatory approval especially in orphan diseases in countries other than Japan.

  5. Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy

    SciTech Connect

    Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R.

    1994-09-01

    Peripheral myelin protein (PMP-22) gene aneuploidy results in Charcot-Marie-Tooth disease Type 1A (CMT1A) and the Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in Japanese patients as well as Caucasian Americans. Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, results when expression of one of at least seven genes is defective. CMT1A, about half of all CMT mutations, is usually associated with a duplication spanning the peripheral myelin protein-22 gene on distal chromosome band 17p11.2. Autosomal dominant HNPP (hereditary pressure and sensory neuropathy, HPSN) results from a deletion of the CMT1A gene region. Multicolor in situ hybridization with PMP-22 gene region probe characterized HNPP deletion reliably and detected all different size duplications reported previously. In summary, 72% of 28 Japanese CMT1 (HMSNI) patients tested had the CMT1A duplication, while none of the CMT2 (HMSNII) or CMT3 (HMSNIII) patients had a duplication. Three cases of HNPP were identified by deletion of the CMT1A gene region on chromosome 17p. HNPP and CMT1A have been reported to result simultaneously from the same unequal recombination event. The lower frequency of HNPP compared to CMT1A suggests that HNPP patients have a lower reproductive fitness than CMT1A patients. This result, along with a CMT1A duplication found in an Asian Indian family, demonstrates the broad geographic distribution and high frequency of PMP-22 gene aneuploidy.

  6. Long-Term Cinacalcet HCl Treatment Improved Bone Metabolism in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism

    PubMed Central

    Shigematsu, Takashi; Akizawa, Tadao; Uchida, Eiji; Tsukamoto, Yusuke; Iwasaki, Manabu; Koshikawa, Shouzo

    2009-01-01

    Background/Aims Few clinical trials conducted with cinacalcet have thoroughly addressed its effects of on bone metabolism. We assessed the effects of cinacalcet on bone markers in Japanese hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). Methods 200 Japanese HD patients with intact PTH (iPTH) levels ≥300 pg/ml were enrolled. The dose of cinacalcet was titrated from 25 up to 100 mg/day to achieve iPTH levels ≤250 pg/ml for 52 weeks. Results At the end of the study visit, 57.8% of patients (115/199) had achieved iPTH levels ≤250 pg/ml. Serum Ca, phosphorus (P) and Ca × P levels decreased rapidly and were maintained throughout the study. At week 52, all bone metabolic markers levels had decreased significantly from baseline. Although bone resorption markers gradually decreased throughout the study period, bone alkaline phosphatase significantly increased during the first 4 weeks and then gradually decreased. Conclusions The time courses of changes in bone markers after cinacalcet treatment resembled those observed after surgical parathyroidectomy (PTx), sometimes described as the hungry bone syndrome, indicating that cinacalcet treatment induces a rapid recovery in bone response to calcium. In addition, long-term efficacy and safety of cinacalcet were also observed in Japanese patients undertaking long-term hemodialysis (167.0 ± 81.4 months). PMID:18797166

  7. Hypothesis of Long-Term Outcome after Coronary Revascularization in Japanese Patients Compared to Multiethnic Groups in the US.

    PubMed

    Inohara, Taku; Kohsaka, Shun; Goto, Masashi; Furukawa, Yutaka; Fukushima, Masanori; Sakata, Ryuzo; Elayda, MacArthur; Wilson, James M; Kimura, Takeshi

    2015-01-01

    Ethnicity has a significant impact on coronary artery disease (CAD). This study investigated the long-term outcomes of Japanese patients undergoing revascularization compared with US patients belonging to multiple ethnic groups. We evaluated clinical outcomes, based on ethnicity, of patients included in the Coronary Revascularization Demonstrating Outcome (CREDO-Kyoto) and the Texas (US) Heart Institute Research Database (THIRDBase) registries. For the analysis, we included 8871 patients from the CREDO-Kyoto registry (median follow-up period [FU], 3.5 years; interquartile range [IQR], 2.6-4.3) and 6717 patients from the THIRDBase registry (FU, 5.2 years; IQR, 3.8-6.5) who underwent percutaneous coronary intervention or bypass surgery. Cox proportional hazard models were constructed to compare the adjusted long-term outcomes for each ethnic group. A total of 8871 Japanese, 5170 Caucasians, 648 African-Americans, 817 Hispanics, and 82 Asian-Americans were identified. When adjusted, Japanese patients had significantly better outcomes than US patients, classified by ethnicity (Caucasians: hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.35-1.79; Hispanics: HR, 1.53; 95% CI, 1.22-1.93; African-Americans: HR, 2.03; 95% CI, 1.62-2.56), except for Asian-Americans (HR, 0.84; 95% CI. 0.38-1.89) who had outcomes similar to Japanese patients. Our findings indicate better survival outcomes in re-vascularized Japanese CAD patients compared to major ethnic groups in the US, including Caucasian, Hispanic, and African-American CAD patients. The characteristics and outcomes of Japanese CAD patients were similar to those of Asian-Americans, despite the sample size limitations in the US dataset.

  8. Hypothesis of Long-Term Outcome after Coronary Revascularization in Japanese Patients Compared to Multiethnic Groups in the US

    PubMed Central

    Inohara, Taku; Kohsaka, Shun; Goto, Masashi; Furukawa, Yutaka; Fukushima, Masanori; Sakata, Ryuzo; Elayda, MacArthur; Wilson, James M.; Kimura, Takeshi

    2015-01-01

    Background Ethnicity has a significant impact on coronary artery disease (CAD). This study investigated the long-term outcomes of Japanese patients undergoing revascularization compared with US patients belonging to multiple ethnic groups. Methods and Results We evaluated clinical outcomes, based on ethnicity, of patients included in the Coronary Revascularization Demonstrating Outcome (CREDO-Kyoto) and the Texas (US) Heart Institute Research Database (THIRDBase) registries. For the analysis, we included 8871 patients from the CREDO-Kyoto registry (median follow-up period [FU], 3.5 years; interquartile range [IQR], 2.6–4.3) and 6717 patients from the THIRDBase registry (FU, 5.2 years; IQR, 3.8–6.5) who underwent percutaneous coronary intervention or bypass surgery. Cox proportional hazard models were constructed to compare the adjusted long-term outcomes for each ethnic group. A total of 8871 Japanese, 5170 Caucasians, 648 African-Americans, 817 Hispanics, and 82 Asian-Americans were identified. When adjusted, Japanese patients had significantly better outcomes than US patients, classified by ethnicity (Caucasians: hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.35–1.79; Hispanics: HR, 1.53; 95% CI, 1.22–1.93; African-Americans: HR, 2.03; 95% CI, 1.62–2.56), except for Asian-Americans (HR, 0.84; 95% CI. 0.38–1.89) who had outcomes similar to Japanese patients. Conclusion Our findings indicate better survival outcomes in re-vascularized Japanese CAD patients compared to major ethnic groups in the US, including Caucasian, Hispanic, and African-American CAD patients. The characteristics and outcomes of Japanese CAD patients were similar to those of Asian-Americans, despite the sample size limitations in the US dataset. PMID:26023784

  9. Safety and efficacy of adalimumab treatment in Japanese patients with psoriasis: Results of SALSA study.

    PubMed

    Asahina, Akihiko; Torii, Hideshi; Ohtsuki, Mamitaro; Tokimoto, Toshimitsu; Hase, Hidenori; Tsuchiya, Tsuyoshi; Shinmura, Yasuhiko; Reyes Servin, Ofelia; Nakagawa, Hidemi

    2016-11-01

    The safety and efficacy of adalimumab were evaluated over 24 weeks in Japanese patients with psoriasis in routine clinical practice. In this multicenter, observational, open-label, postmarketing study, primary efficacy measures included the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI) in all patients with psoriasis. In patients with psoriatic arthritis (PsA), the 28-joint Disease Activity Score (DAS28) and the visual analog scale (VAS) pain were also evaluated. Safety was assessed based on the frequency of adverse drug reactions (ADR). Among patients with psoriasis evaluated for efficacy (n = 604), significant improvements from baseline were observed in mean PASI and DLQI scores at weeks 16 and 24 (all P < 0.0001). Furthermore, in psoriasis patients without PsA, the PASI 75/90 response rates were 55.9%/28.4% at week 16 (n = 306) and 65.6%/43.3% at week 24 (n = 270), respectively. In patients with PsA evaluable for effectiveness, significant improvements from baseline were observed in PASI, DAS28 erythrocyte sedimentation rate, DAS28 C-reactive protein and VAS pain at weeks 16 and 24 (all P < 0.0001). ADR and serious ADR were reported by 26.1% and 3.3%, respectively, of 731 safety evaluable patients with psoriasis; no unexpected safety findings were noted. The safety profile and effectiveness of adalimumab for the treatment of psoriasis in a routine clinical setting were as expected in Japanese patients. © 2016 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

  10. Evaluating Japanese patients with the Marfan syndrome using high-throughput microarray-based mutational analysis of fibrillin-1 gene.

    PubMed

    Ogawa, Naomi; Imai, Yasushi; Takahashi, Yuji; Nawata, Kan; Hara, Kazuo; Nishimura, Hiroshi; Kato, Masayoshi; Takeda, Norifumi; Kohro, Takahide; Morita, Hiroyuki; Taketani, Tsuyoshi; Morota, Tetsuro; Yamazaki, Tsutomu; Goto, Jun; Tsuji, Shoji; Takamoto, Shinichi; Nagai, Ryozo; Hirata, Yasunobu

    2011-12-15

    Marfan syndrome (MS) is an inherited connective tissue disorder, and detailed evaluations of multiple organ systems are required for its diagnosis. Genetic testing of the disease-causing fibrillin-1 gene (FBN1) is also important in this diagnostic scheme. The aim of this study was to define the clinical characteristics of Japanese patients with MS and enable the efficient and accurate diagnosis of MS with mutational analysis using a high-throughput microarray-based resequencing system. Fifty-three Japanese probands were recruited, and their clinical characteristics were evaluated using the Ghent criteria. For mutational analysis, an oligonucleotide microarray was designed to interrogate FBN1, and the entire exon and exon-intron boundaries of FBN1 were sequenced. Clinical evaluation revealed more pulmonary phenotypes and fewer skeletal phenotypes in Japanese patients with MS compared to Caucasians. The microarray-based resequencing system detected 35 kinds of mutations, including 23 new mutations. The mutation detection rate for patients who fulfilled the Ghent criteria reached 71%. Of note, splicing mutations accounted for 19% of all mutations, which is more than previously reported. In conclusion, this comprehensive approach successfully detected clinical phenotypes of Japanese patients with MS and demonstrated the usefulness and feasibility of this microarray-based high-throughput resequencing system for mutational analysis of MS. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Creutzfeldt-Jakob disease with a codon 210 mutation: first pathological observation in a Japanese patient.

    PubMed

    Tajima, Yasutaka; Satoh, Chika; Mito, Yasunori; Kitamoto, Tetsuyuki

    2014-01-01

    We herein report a case of Creutzfeldt-Jakob disease (CJD) with a V210I mutation and discuss the pathological findings. The patient's clinical course was quite similar to that of patients with sporadic CJD. Diffusion-weighted magnetic resonance imaging (MRI) disclosed a high signal intensity in the basal ganglia and cerebral cortices. Pathologically, spongiform degeneration of neurons and their processes with reactive astrocytosis was observed. Prion protein immunostaining revealed diffuse positive and plaque-type patterns. Only one Japanese case of CJD with this type of mutation has been reported to date, but without any pathological examination results. Therefore, this report is considered to be highly significant for understanding CJD.

  12. Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I–II essential hypertension: a randomized, double-blind clinical study

    PubMed Central

    Rakugi, Hiromi; Enya, Kazuaki; Sugiura, Kenkichi; Ikeda, Yoshinori

    2012-01-01

    Azilsartan is a novel angiotensin receptor blocker being developed for hypertension treatment. This 16-week, multicenter, randomized, double-blind study compared the efficacy and safety of azilsartan (20–40 mg once daily by forced titration) and its ability to provide 24-h blood pressure (BP) control, with that of candesartan cilexetil (candesartan; 8–12 mg once daily by forced titration) in 622 Japanese patients with grade I–II essential hypertension. Efficacy was evaluated by clinic-measured sitting BP, and by ambulatory BP monitoring (ABPM) at week 14. Participants (mean age: 57 years, 61% males) had a mean baseline sitting BP of 159.8/100.4 mm Hg. The mean change from baseline in sitting diastolic BP at week 16 (primary endpoint) was −12.4 mm Hg in the azilsartan group and −9.8 mm Hg in the candesartan group, demonstrating a statistically significant greater reduction with azilsartan vs. candesartan (difference: −2.6 mm Hg, 95% confidence interval (CI): −4.08 to −1.22 mm Hg, P=0.0003). The week 16 (secondary endpoint) mean change from baseline in sitting systolic BP was −21.8 mm Hg and −17.5 mm Hg, respectively, a significant decrease with azilsartan vs. candesartan (difference: −4.4 mm Hg, 95% CI: −6.53 to −2.20 mm Hg, P<0.0001). On ABPM, the week 14 mean changes from baseline in diastolic and systolic BP were also significantly greater with azilsartan over a 24-h period, and during the daytime, night-time and early morning. Safety and tolerability were similar among the two groups. These data demonstrate that once-daily azilsartan provides a more potent 24-h sustained antihypertensive effect than that of candesartan but with equivalent safety. PMID:22278628

  13. Historical chronology of basic and clinical research in diabetic nephropathy and contributions of Japanese scientists.

    PubMed

    Wada, Jun; Makino, Hirofumi

    2009-10-01

    The most problematic issue in clinical nephrology worldwide is the relentless and progressive increase in patients with end-stage renal disease (ESRD). Diabetic nephropathy has considerable impact on society in the areas of public health and social economy; many scientists are involved in research for the elucidation of the pathogenesis of diabetic nephropathy and for the prevention and cure of the disease. In contrast, diabetic nephropathy was a neglected or ignored disease in the historical era, and few dedicated physicians recognized the disease process of diabetic nephropathy. In this review, we look back on the history of basic and clinical research on diabetic nephropathy and survey the recent progress of the research, especially focusing on the contribution of Japanese scientists.

  14. Safety and benefits of a tablet combining losartan and hydrochlorothiazide in Japanese diabetic patients with hypertension.

    PubMed

    Kinouchi, Kenichiro; Ichihara, Atsuhiro; Sakoda, Mariyo; Kurauchi-Mito, Asako; Itoh, Hiroshi

    2009-12-01

    This study was conducted to determine the effects of a tablet combining losartan/hydrochlorothiazide (L/HCTZ) in comparison with losartan alone in Japanese diabetic patients with hypertension. Thirty consecutive Japanese diabetic patients with hypertension were randomly assigned to group A, receiving losartan alone for the first 3 months, then L/HCTZ for the next 3 months, or group B, receiving L/HCTZ for the first 3 months, then losartan alone for the next 3 months. Clinical and biological parameters were obtained before, and 3 and 6 months after the start of this study. The decreases in systolic and diastolic blood pressure (BP) during treatment with L/HCTZ were significantly greater than in treatment with losartan alone. Both treatments significantly and similarly decreased urinary albumin excretion, the cardio-ankle vascular index (CAVI) and augmentation index (AI). There was no significant difference in metabolic change during both the mono- and combination pharmacotherapies. The tablet combining L/HCTZ significantly reduced systolic and diastolic BP compared with the losartan monotherapy, and offered benefits similar to losartan monotherapy for albuminuria, arterial stiffness assessed by the CAVI and AI, and metabolic effects. Thus, the L/HCTZ tablet could be a useful drug for Japanese diabetic patients with hypertension.

  15. Randomized clinical trial comparing 5% and 1% topical minoxidil for the treatment of androgenetic alopecia in Japanese men.

    PubMed

    Tsuboi, Ryoji; Arano, Osamu; Nishikawa, Tooru; Yamada, Hidekazu; Katsuoka, Kensei

    2009-08-01

    Minoxidil is efficacious in inducing hair growth in patients with androgenetic alopecia by inducing hair follicles to undergo transition from the early to late anagen phase. Although the efficacy of 1% topical minoxidil has been confirmed in Japan, no controlled study of 5% topical minoxidil has been conducted using male Japanese subjects. The objective of this trial was to verify the superiority in clinical efficacy of 5% topical minoxidil to 1% topical minoxidil in a double-blind controlled study with male, Japanese androgenetic alopecia patients as the subjects. The trial included 300 Japanese male patients aged 20 years or older with androgenetic alopecia who were administered either 5% topical minoxidil (n = 150) or 1% topical minoxidil (n = 150) for 24 weeks. The mean change from the baseline in non-vellus hair/cm(2), the primary efficacy variable, was 26.4 (n = 142) in the 5% topical minoxidil group and 21.2 (n = 144) in the 1% topical minoxidil group at 16 weeks, the main time point for the evaluation. The difference between the groups was significant (P = 0.020). The incidence of adverse events was 8.7% (13/150) in the 5% group and 5.3% (8/150) in the 1% group, with no significant difference between the groups (chi(2)-test: P = 0.258). Our findings confirmed the superiority of 5% topical minoxidil to 1% topical minoxidil in treating Japanese men with androgenetic alopecia.

  16. Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X.

    PubMed

    Miyamoto, T; Kanazawa, N; Kato, S; Kawakami, M; Inoue, Y; Kuhara, T; Inoue, T; Takeshita, K; Tsujino, S

    2001-01-01

    Patients with mitochondrial ornithine transporter deficiency (or HHH syndrome) present with various neurological symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma due to hyperammonemia. We previously described three novel mutations in the ORNT1 gene in Japanese patients with HHH syndrome. In this article, we report a new patient with HHH syndrome, a 52-year-old woman, who had the typical clinical features, except for an absence of mental retardation. When we screened this patient, as well as a previously described Japanese patient, for mutations in the ORNT1 gene, we found that both were homozygous for a nonsense mutation (R179X). Furthermore, reverse transcription (RT)-polymerase chain reaction (PCR) of fibroblast RNA from one patient showed exon 4 skipping, as had been observed in a previously reported patient with R179X. These results, together with the findings in our previous report, show that, in three of our five reported Japanese HHH patients (six of ten alleles), R179X is present, suggesting that this is a common mutation in Japanese patients with HHH syndrome.

  17. The Japanese Postmarketing Adverse Event Relief System: A Confluence of Regulatory Science, the Legal System, and Clinical Pharmacology.

    PubMed

    Tominaga, T; Miyazaki, S; Oniyama, Y; Weber, A D; Kondo, T

    2016-10-13

    The Japanese Postmarketing Relief System provides for compensation to patients with adverse reactions, based on the acknowledgment that unpredicted adverse events occur inevitably once a drug is marketed. The system also provides new knowledge about the benefit-risk profile of a drug that may be incorporated into product labeling. The system relies on causality assessments that are based on sound clinical pharmacology principles. The system may serve as a model for other countries' healthcare systems.

  18. Validity and reliability of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) in Japanese patients with bipolar disorder.

    PubMed

    Toyoshima, Kuniyoshi; Fujii, Yutaka; Mitsui, Nobuyuki; Kako, Yuki; Asakura, Satoshi; Martinez-Aran, Anabel; Vieta, Eduard; Kusumi, Ichiro

    2017-08-01

    In Japan, there are currently no reliable rating scales for the evaluation of subjective cognitive impairment in patients with bipolar disorder. We studied the relationship between the Japanese version of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and objective cognitive assessments in patients with bipolar disorder. We further assessed the reliability and validity of the COBRA. Forty-one patients, aged 16-64, in a remission period of bipolar disorder were recruited from Hokkaido University Hospital in Sapporo, Japan. The COBRA (Japanese version) and Frankfurt Complaint Questionnaire (FCQ), the gold standard in subjective cognitive assessment, were administered. A battery of neuropsychological tests was employed to measure objective cognitive impairment. Correlations among the COBRA, FCQ, and neuropsychological tests were determined using Spearman's correlation coefficient. The Japanese version of the COBRA had high internal consistency, good retest reliability, and concurrent validity-as indicated by a strong correlation with the FCQ. A significant correlation was also observed between the COBRA and objective cognitive measurements of processing speed. These findings are the first to demonstrate that the Japanese version of the COBRA may be clinically useful as a subjective cognitive impairment rating scale in Japanese patients with bipolar disorder. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  19. [Comparison of clinical efficacy and cost-quality of antihistamines in early treatment for Japanese cedar pollinosis].

    PubMed

    Kakutani, Chieko; Ogino, Satoshi; Ikeda, Hiroki; Enomoto, Tadao

    2006-05-01

    Japanese cedar pollinosis (JCP) affects more than 16% of the Japanese population. The estimated direct and indirect costs for this disease totaled 286 billion yen in 1998. In JCP therapy, antihistamines are first line agents. It is well known that starting treatment for JCP with antihistamines before initial day of the pollen scattering can relieve nasal symptom severity during pollen season. The aim of this study is to assess the clinical efficacy and cost-quality of 7 major second-generation antihistamines in early treatment for Japanese cedar pollinosis (JCP). Patients were randomly selected from 16 ENT clinical sites in Osaka and Wakayama between February 24 and March 8, 2003 (peak pollen season). Effectiveness was assessed using patient'ratings of nasal and ocular symptoms and overall assessment in their condition compared to previous season ones. Costs include direct costs of the drugs used for treatment to JCP from January to March. One hundred seventy-five patients who were treated with antihistamine monotherapy (azelastine: n=15, cetirizine: n=15, ebastine: n=36, epinastine: n=16, fexofenadine: n=16, loratadine: n=60, oxatomide: n=17) and 510 non-treatment patients were evaluated. Among 8 groups, there were significant differences in sneezing, rhinorrhea, ocular itching and overall health condition. However, among 7 monotherapy groups, there were no differences in each symptom or the overall assessment. In cost-quality analysis, there were significant differences in a cost for each effective patient (defined as those with improvement in their overall condition) among 7 drugs. The top three cost-efficacious drugs resulted in azelastine, loratadine and fexofenadine. These results show that there were no significant differences in clinical efficacy in early treatment for JCP among 7 antihistamines. But Japanese National Health Insurance drug price scheme led to significant differences in cost-quality.

  20. Experience with alendronate treatment for 7 years among Japanese men with osteoporosis or osteopenia and clinical risk factors for fractures.

    PubMed

    Iwamoto, Jun; Uzawa, Mitsuyoshi

    2016-01-01

    A retrospective study was performed to evaluate the outcome of alendronate treatment for 7 years among Japanese men with osteoporosis or osteopenia and clinical risk factors for fractures. Thirty-five Japanese men with osteoporosis or osteopenia and clinical risk factors for fractures (mean age at baseline 58.2 years) who had been treated with alendronate for over 7 years in our outpatient clinic were analyzed. The lumbar spine or total hip bone mineral density (BMD) was measured using dual energy X-ray absorptiometry; the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) and the serum levels of alkaline phosphatase (ALP) were monitored; the incidence of fractures during the 7-year treatment period was then assessed. The urinary NTX and serum ALP levels decreased (-46.1% at 3 months and -21.1% at 7 years, respectively) and the lumbar spine and total hip BMD increased (+14.2 and +10.1% at 7 years, respectively), compared with the baseline values. Four patients (11.4%) experienced vertebral fractures, and one patient (2.9%) experienced a nonvertebral fracture. No serious adverse events were observed, including osteonecrosis of the jaw or atypical femoral fractures. These results suggested that alendronate suppressed bone turnover and increased the lumbar spine and total hip BMD from the baseline values over the course of the 7-year treatment period without causing any severe adverse events in Japanese men with osteoporosis or osteopenia and clinical risk factors for fractures.

  1. Cytogenetic differences in breast cancer samples between German and Japanese patients

    PubMed Central

    Packeisen, J; Nakachi, K; Boecker, W; Brandt, B; Buerger, H

    2005-01-01

    Background: Japanese and German breast cancer cases differ substantially in the frequency of egfr amplification. Aims: To unravel further the cytogenetic differences between Japanese and German breast cancer cases. Methods: Forty one Japanese breast cancer cases were evaluated by means of comparative genomic hybridisation (CGH). The results were compared with the CGH results from 161 German breast cancer cases. Results: The mean number of genetic alterations/case was significantly higher in German premenopausal patients with breast cancer than in their Japanese counterparts. Japanese breast cancer cases revealed a higher number of chromosome 17p losses. Losses of 8p were associated with oestrogen receptor (ER) negativity in Japanese patients with breast cancer, whereas in the German patients gains of 3q and 6q were associated with the lack of ER expression. Conclusions: The interethnic differences of invasive breast cancer are reflected by cytogenetic aberrations, which are also associated with the differential expression of the ER. PMID:16189159

  2. Prevalence of Fabry disease and GLA c.196G>C variant in Japanese stroke patients.

    PubMed

    Nagamatsu, Kiyoshiro; Sekijima, Yoshiki; Nakamura, Katsuya; Nakamura, Kimitoshi; Hattori, Kiyoko; Ota, Masao; Shimizu, Yusaku; Endo, Fumio; Ikeda, Shu-Ichi

    2017-03-09

    Fabry disease is an important underlying disease in young cryptogenic stroke patients. However, little is known regarding the frequency of Fabry disease in the general stroke population, especially in elderly patients. A total of 588 stroke patients (61.7% men; average age 74.1±12.5 years) were enrolled in this prospective study. Blood samples were obtained to produce blood spots to determine α-galactosidase A (α-GalA) activity and for GLA gene analysis. One 65-year-old female patient had a known GLA gene mutation, c.2T>C (p.M1T), causing Fabry disease. Five male patients and two female patients had GLA c.196G>C (p.E66Q) variant, which is not associated with the full clinical manifestations of Fabry disease. The allele frequency of GLA c.196G>C was significantly higher in male patients with small-vessel occlusion (odds ratio 3.95, P=0.048) and non-cardioembolism (odds ratio 4.08, P=0.012) than that in the general Japanese population. Fabry disease is rare in the general Japanese stroke population. However, screening identified one elderly female patient with Fabry disease. GLA c.196G>C variant is a genetic risk factor for cerebral small-vessel occlusion and non-cardioembolism in Japanese males but not in females.Journal of Human Genetics advance online publication, 9 March 2017; doi:10.1038/jhg.2017.31.

  3. Comparable pharmacodynamics, efficacy, and safety of linagliptin 5 mg among Japanese, Asian and white patients with type 2 diabetes.

    PubMed

    Sarashina, Akiko; Friedrich, Christian; Crowe, Susanne; Patel, Sanjay; Graefe-Mody, Ulrike; Hayashi, Naoyuki; Horie, Yoshiharu

    2016-09-01

    The efficacy and safety of drugs can vary between different races or ethnic populations because of differences in the relationship of dose to exposure, pharmacodynamic response or clinical efficacy and safety. In the present post-hoc analysis, we assessed the influence of race on the pharmacokinetics, pharmacodynamics, efficacy and safety of monotherapy with the dipeptidyl peptidase-4 inhibitor, linagliptin, in patients with type 2 diabetes enrolled in two comparable, previously reported randomized phase III trials. Study 1 (with a 12-week placebo-controlled phase) recruited Japanese patients only (linagliptin, n = 159; placebo, n = 80); study 2 (24-week trial) enrolled Asian (non-Japanese; linagliptin, n = 156; placebo, n = 76) and white patients (linagliptin, n = 180; placebo, n = 90). Linagliptin trough concentrations were equivalent across study and race groups, and were higher than half-maximal inhibitory concentration, resulting in dipeptidyl peptidase-4 inhibition >80% at trough. Linagliptin inhibited plasma dipeptidyl peptidase-4 activity to a similar degree in study 1 and study 2. Linagliptin reduced fasting plasma glucose concentrations by a similar magnitude across groups, leading to clinically relevant reductions in glycated hemoglobin in all groups. Glycated hemoglobin levels decreased to a slightly greater extent in study 1 (Japanese) and in Asian (non-Japanese) patients from study 2. Linagliptin had a favorable safety profile in each race group. Trough exposure, pharmacodynamic response, and efficacy and safety of linagliptin monotherapy were comparable among Japanese, Asian (non-Japanese) and white patients, confirming that the recommended 5-mg once-daily dose of linagliptin is appropriate for use among different race groups. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  4. Investigation of emtricitabine-associated skin pigmentation and safety in HIV-1-infected Japanese patients.

    PubMed

    Shirasaka, Takuma; Tadokoro, Taketsugu; Yamamoto, Yasuyuki; Fukutake, Katsuyuki; Kato, Yukihiko; Odawara, Takashi; Nakamura, Tetsuya; Ajisawa, Atsushi; Negishi, Masayoshi

    2011-10-01

    Emtricitabine (FTC) has been reported to cause skin pigmentation (SP), and the incidence of SP associated with FTC varied with ethnicity, with a higher rate in African-American patients (8%). We assessed the incidence of SP in Japanese HIV-1-infected patients receiving combination antiretroviral therapy (cART) with FTC for a period of 48 weeks and confirmed new findings of FTC-associated SP, including pathological characteristics. This was a multicenter, prospective, longitudinal non-randomized study. We evaluated the appearance of SP at 48 weeks as the primary endpoint in 155 Japanese patients, and secondary endpoints included the characteristics of the SP (location, color tone, size, and progression). Six cases (3.9%) of SP occurred at a median of 124 days (range: 7-259 days) within 48 weeks. The SP looked like an isolated dark spot, 1-2 mm in diameter, mainly on the hands and/or feet. The severity of all the SPs was mild. Each SP had disappeared or faded at a median of 112 days (range: 28-315 days) with continued FTC. FTC-associated SP was considered to be lentigo simplex by dermatoscopy and pathological appearance. In summary, the incidence of FTC-associated SP in Japanese patients was 3.9%, and was comparable to the previously reported incidence in Asian patients (4%). FTC-associated SP was not associated with any clinically significant symptoms and has little clinical significance.

  5. Application of Empowerment Scale to patients with schizophrenia: Japanese experience.

    PubMed

    Yamada, Sumie; Suzuki, Kunifumi

    2007-12-01

    Rogers et al. invented the Empowerment Scale, and conducted a factor analysis, which found five factors: self-esteem, power, activism, righteous anger and optimism. Hata et al. translated this scale into Japanese and named it Empowerment Scale-J. They found that the score of the righteous anger factor does not have a significant correlation with the overall score of the Empowerment Score-J. With the aim of clarifying the characteristics of the Empowerment Scale-J, the purpose of the present study was to assess the levels of empowerment in 72 Japanese patients with chronic schizophrenia using the scale, and examine the relationship between the results of the scale and the results of the following two batteries: Social Adjustment Scale II (SAS II), and Expanded Attributional Style Questionnaire (EASQ; a questionnaire to assess some aspects of attitude toward negative circumstances). Four results were obtained as follows. No significant correlation was found between the score of righteous anger factor and overall score. No significant correlation was found between the Empowerment Scale-J score and the degree of social adjustment. Significant correlations were found between some subscales of Empowerment Scale-J and the degree of social adjustments: self-esteem and optimism, but inverse correlations were obtained between the power factor and the righteous anger factor and the degree of social adjustment. Results for the EASQ showed that subjects with a higher righteous anger score have a tendency opposite to that of subjects with higher social adjustment. On the basis of these results it is suggested that behavior related to the righteous anger among Japanese persons with schizophrenia may have some negative influence on their social adaptation and that in applying Empowerment scale-J attention should be paid to the significance of the righteous anger factor.

  6. Detecting gene mutations in Japanese Alzheimer's patients by semiconductor sequencing.

    PubMed

    Yagi, Ryoichi; Miyamoto, Ryosuke; Morino, Hiroyuki; Izumi, Yuishin; Kuramochi, Masahito; Kurashige, Takashi; Maruyama, Hirofumi; Mizuno, Noriyoshi; Kurihara, Hidemi; Kawakami, Hideshi

    2014-07-01

    Alzheimer's disease (AD) is the most common form of dementia. To date, several genes have been identified as the cause of AD, including PSEN1, PSEN2, and APP. The association between APOE and late-onset AD has also been reported. We here used a bench top next-generation sequencer, which uses an integrated semiconductor device, detects hydrogen ions, and operates at a high-speed using nonoptical technology. We examined 45 Japanese AD patients with positive family histories, and 29 sporadic patients with early onset (<60-year-old). Causative mutations were detected in 5 patients in the familial group (11%). Three patients had a known heterozygous missense mutation in the PSEN1 gene (p.H163R). Two patients from 1 family had a novel heterozygous missense mutation in the PSEN1 gene (p.F386L). In the early onset group, 1 patient carrying homozygous APOEε4 had a novel heterozygous missense mutation in the PSEN2 gene (p.T421M). Approximately 43% patients were APOEε4 positive in our study. This new sequencing technology is useful for detecting genetic variations in familial AD.

  7. A novel mutation, P126R, in a Japanese patient with HHH syndrome.

    PubMed

    Miyamoto, Takeshi; Kanazawa, Naomi; Hayakawa, Chiemi; Tsujino, Seiichi

    2002-01-01

    Mitochondrial ornithine transporter deficiency, or HHH syndrome, is a metabolic disorder resulting in various neurologic symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma caused by hyperammonemia. Several mutations have been reported in the ORNT1 gene encoding mitochondrial ornithine transporter of patients with this disorder. In this article, we report a new patient, a male 15 years of age, who had typical clinical features of HHH syndrome. Because the patient did not have any of the three mutations previously described in other Japanese patients with HHH syndrome, and the only material available from the patient was peripheral leukocytes, we established a genomic polymerase chain reaction method using intronic primers to amplify every exon of the ORNT1 gene, and we directly sequenced the polymerase chain reaction products. Using this method, we documented a novel mutation in this patient, P126R, and demonstrated that HHH syndrome is genetically heterogeneous, even in the Japanese population.

  8. Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens' antibacterial susceptibility.

    PubMed

    Yanagihara, Katsunori; Kadota, Junichi; Aoki, Nobuki; Matsumoto, Tetsuya; Yoshida, Masaki; Yagisawa, Morimasa; Oguri, Toyoko; Sato, Junko; Ogasawara, Kazuhiko; Wakamura, Tomotaro; Sunakawa, Keisuke; Watanabe, Akira; Iwata, Satoshi; Kaku, Mitsuo; Hanaki, Hideaki; Ohsaki, Yoshinobu; Watari, Tomohisa; Toyoshima, Eri; Takeuchi, Kenichi; Shiokoshi, Mayumi; Takeda, Hiroaki; Miki, Makoto; Kumagai, Toshio; Nakanowatari, Susumu; Takahashi, Hiroshi; Utagawa, Mutsuko; Nishiya, Hajime; Kawakami, Sayoko; Kobayashi, Nobuyuki; Takasaki, Jin; Mezaki, Kazuhisa; Konosaki, Hisami; Aoki, Yasuko; Yamamoto, Yumiko; Shoji, Michi; Goto, Hajime; Saraya, Takeshi; Kurai, Daisuke; Okazaki, Mitsuhiro; Niki, Yoshihito; Yoshida, Koichiro; Kawana, Akihiko; Saionji, Katsu; Fujikura, Yuji; Miyazawa, Naoki; Kudo, Makoto; Sato, Yoshimi; Yamamoto, Masaki; Yoshida, Takashi; Nakamura, Masahiko; Tsukada, Hiroki; Imai, Yumiko; Tsukada, Ayami; Kawasaki, Satoshi; Honma, Yasuo; Yamamoto, Toshinobu; Ban, Nobuyoshi; Mikamo, Hiroshige; Sawamura, Haruki; Miyara, Takayuki; Toda, Hirofumi; Sato, Kaori; Nakamura, Tadahiro; Fujikawa, Yasunori; Mitsuno, Noriko; Mikasa, Keiichi; Kasahara, Kei; Sano, Reiko; Sugimoto, Keisuke; Asari, Seishi; Nishi, Isao; Toyokawa, Masahiro; Miyashita, Naoyuki; Koguchi, Yutaka; Kusano, Nobuchika; Mihara, Eiichirou; Kuwabara, Masao; Watanabe, Yaeko; Kawasaki, Yuji; Takeda, Kenichi; Tokuyasu, Hirokazu; Masui, Kayoko; Negayama, Kiyoshi; Hiramatsu, Kazufumi; Aoki, Yosuke; Fukuoka, Mami; Magarifuchi, Hiroki; Nagasawa, Zenzo; Suga, Moritaka; Muranaka, Hiroyuki; Morinaga, Yoshitomo; Honda, Junichi; Fujita, Masaki

    2015-06-01

    The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents. Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S. pneumoniae were 1.1% and 0.0%, respectively. Among H. influenzae, 17.6% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be β-lactamase-non-producing ABPC-resistant and 11.0% to be β-lactamase-producing ABPC-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 2.9% and 0.6%, respectively. Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

  9. Japanese experience with clinical trails of fast neutrons

    SciTech Connect

    Tsunemoto, H.; Arai, T.; Morita, S.; Ishikawa, T.; Aoki, Y.; Takada, N.; Kamata, S.

    1982-12-01

    Between November, 1975 and November, 1981, 825 patients were treated with 30 MeV (d-Be) neutrons at the National Institute of Radiological Sciences, Chiba. At the Institute of Medical Science, Tokyo, 302 patients were referred to the Radiation Therapy department and were treated with 16 MeV (d-Be) neutrons. The emphasis of these clinical trials with fast neutrons was placed on the estimation of the effect of fast neutrons for locally advanced cancers or radioresistant cancers, and on evaluation of the rate of complication of normal tissues following irradiaton with fast neutrons. Results were evaluated for patients with previously untreated cancer; local control of the tumor was observed in 59.1%. Complications requiring medical care developed in only 32 patients. Patients who had received pre- or postoperative irradiation were excluded from this evaluation. Late reaction of soft tissue seemed to be more severe than that observed with photon beams. The results also suggest that for carcinoma of the larynx, esophagus, uterine cervix, Pancoasts's tumor of the lung and osteosarcoma, fast neutrons were considered to be effectively applied in this randomized clinical trial. For carcinoma of the larynx, a fast nuetron boost was effectively delivered, although an interstitial implant was necessarily combined with fast neutrons for carcinoma of the tongue. The cumulative survival rate of the patients with carcinoma of the esophagus treated with fast neutrons was 26% compared to the survival rate of 10.5% obtained using photons. This was supported by evidence from the pathological studies that showed that the tumor cells which had deeply invaded into the esophagus were effectively destroyed when fast neutrons were applied.

  10. Japanese experience with clinical trials of fast neutrons

    SciTech Connect

    Tsunemoto, H.; Arai, T.; Morita, S.; Ishikawa, T.; Aoki, Y.; Takada, N.; Kamata, S.

    1982-12-01

    Between November, 1975 and November, 1981, 825 patients were treated with 30 MeV (d-Be) neutrons at the National Institute of Radiological Sciences, Chiba. At the Institute of Medical Science, Tokyo, 302 patients were referred to the Radiation Therapy department and were treated with 16 MeV (d-Be) neutrons. The emphasis of these clinical trials with fast neutrons was placed on the estimation of the effect of fast neutrons for locally advanced cancers or radioresistant cancers, and on evaluation of the rate of complication of normal tissues following irradiation with fast neutrons. Results were evaluated for patients with previously untreated cancer; local control of the tumor was observed in 59.1%. Complications requiring medical care developed in only 32 patients. Late reaction of soft tissue seemed to be more severe than that observed with photon beams. The results also suggest that for carcinoma of the larynx, esophagus, uterine cervix, Pancoast's tumor of the lung and osteosarcoma, fast neutrons were considered to be effectively applied in this randomized clinical trial. For carcinoma of the larynx, a fast neutron boost was effectively delivered, although an interstitial implant was necessarily combined with fast neutrons for carcinoma of the tongue. The cumulative survival rate of the patients with carcinoma of the esophagus treated with fast neutrons of 26% compared to the survival rate of 10.5% obtained using photons. The results also indicate that local control and relief of the symptom related to Pancoast's tumor of the lung seemed to be better with neutrons than with photons. For patients suffering from osteosarcoma, the surgical procedures preserving the function of the leg and arm were studied according to the better local control rate of the tumor following fast neutron beam therapy.

  11. Japanese nurses' perceptions about disclosure of information at the patients' end of life.

    PubMed

    Konishi, E; Davis, A J

    1999-09-01

    Information disclosure at the end of life is one of the most debated ethical issues in Japan. This paper, using data from a larger questionnaire survey in which 147 Japanese nurses participated, describes nurses' perceptions about this issue. The nurses perceived that non-disclosure of impending death information to patients was the norm in Japan due to its traditional values. This non-disclosure of information has various impacts on clinical nurses. Tension was evident between the Japanese traditional concepts supported by some nurses and the shift toward Western cultural and ethical values supported by other nurses. The nurses confronted uninformed patients who became suspicious, isolated, angry, or died unprepared for their life's ending. The nurses were placed in the middle between the patient and the family, as nurses became keepers of family secrets, or between nurses' ethical obligations to the patient and those of the institution. The nurses had the belief that at the patient's end of life, it is important to change health professionals' attitude from curing to caring.

  12. Heterogeneity of patients receiving artificial nutrition in Japanese psychiatric hospitals: a cross-sectional study.

    PubMed

    Hirao, Akihiko; Abe, Keiichi; Takayama, Keiko; Kondo, Keiko; Yokota, Osamu; Sato, Yoshiki; Norikiyo, Taizo; Sato, Soichiro; Nakashima, Tadao; Hayashi, Hideki; Nakata, Kenji; Asaba, Hiroyuki; Tanaka, Kazuyoshi; Tanaka, Ritsuho; Morisada, Yumi; Itakura, Hisakazu; Honda, Hajime; Okabe, Nobuyuki; Oshima, Etsuko; Terada, Seishi

    2016-11-01

    Artificial nutrition, including tube feeding, continues to be given to dementia patients in numerous geriatric facilities in Japan. However, the clinical characteristics of patients receiving artificial nutrition have not been fully investigated. Therefore, we tried to evaluate the clinical features of those patients in this study. Various clinical characteristics of all inpatients at 18 of 20 psychiatric hospitals in Okayama Prefecture, Japan, with a percutaneous endoscopic gastrostomy tube, nasogastric tube, or total parenteral nutrition were evaluated. Two hundred twenty-one patients (5.4% of all inpatients) had been receiving artificial nutrition for more than 1 month, and 187 (130 women, 57 men; 84.6% of 221 patients) were fully investigated. The mean age was 78.3 years old, and the mean duration of artificial nutrition was 29.8 months. Eighty-four patients (44.7% of 187 patients) were receiving artificial nutrition for more than 2 years. Patients with Alzheimer's disease (n = 78) formed the biggest group, schizophrenia (n = 37) the second, and vascular dementia (n = 26) the third. About one-fifth of the subjects receiving artificial nutrition were in a vegetative state. More than a few patients with mental disorders, including schizophrenia, also received long-term artificial nutrition. We should pay more attention to chronic dysphasia syndrome in mental disorders. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.

  13. Germline mutations in Japanese familial pancreatic cancer patients

    PubMed Central

    Shimizu, Kyoko; Furuse, Junji; Kubo, Emi; Ohmoto, Akihiro; Suzuki, Masami; Hruban, Ralph H.; Okusaka, Takuji; Morizane, Chigusa; Furukawa, Toru

    2016-01-01

    Clinicopathologic and genetic features of familial pancreatic cancer (FPC) in Asian countries remain largely unknown. The main purpose of this study was to determine the prevalence of FPC and to define causative FPC-predisposition genes in a Japanese cohort with pancreatic ductal adenocarcinoma (PDAC). We reviewed 1,197 patients with a pathologically proven PDAC and found that 88 (7.3%) were FPC patients who had at least one first-degree relative with PDAC. There were no significant differences between the FPC cases and sporadic cases in terms of gender, age, tumor location, stage, family history of any cancer except PDAC, and personal history of smoking, other cancers, diabetes mellitus and chronic pancreatitis. In the FPC patients, we then investigated the prevalence of germline mutations in 21 genes associated with hereditary predispositions for pancreatic, breast and ovarian cancers by means of the next-generation sequencing using a custom multiple-gene panel. We found that eight (14.5%) of the 54 FPC patients with available germline DNA carried deleterious mutations in BRCA2, PALB2, ATM, or MLH1. These results indicate that a significant fraction of patients with PDAC in Japan have a family history of pancreatic cancer, and some of them harbor deleterious causative mutations in known FPC predisposition genes. PMID:27732944

  14. Efficacy and safety of ibrutinib in Japanese patients with relapsed or refractory mantle cell lymphoma.

    PubMed

    Maruyama, Dai; Nagai, Hirokazu; Fukuhara, Noriko; Kitano, Toshiyuki; Ishikawa, Takayuki; Shibayama, Hirohiko; Choi, Ilseung; Hatake, Kiyohiko; Uchida, Toshiki; Nishikori, Momoko; Kinoshita, Tomohiro; Matsuno, Yoshihiro; Nishikawa, Tomoaki; Takahara, Satoko; Tobinai, Kensei

    2016-12-01

    In this multicenter, single-arm, phase II study, the efficacy and safety of ibrutinib were examined in Japanese patients with relapsed or refractory mantle cell lymphoma (MCL). Patients (age ≥20 years) with relapsed or refractory MCL who had progressed after receiving at least one prior treatment regimen, were enrolled. Patients were treated with oral ibrutinib (560 mg once daily; 28-day cycle) until disease progression (or relapse), unacceptable toxicity, or study end. The primary end-point was overall response rate. Secondary end-points included duration of response (DOR), time to response, progression-free survival (PFS), overall survival, and safety. Of the 16 patients who received treatment, 5 patients discontinued the study (progressive disease, 4; sepsis, 1). Median duration of ibrutinib exposure was 6.5 months (range, 2.8-8.3 months). The overall response rate was 87.5% (90% confidence interval, 65.6-97.7; complete response = 2 [12.5%]; partial response = 12 [75.0%]). Median time to response for all responders (n = 14) was 1.8 months (range, 0.7-5.3 months). The median DOR and PFS were not estimable due to censoring (range: DOR, 1.1-6.4+ months; PFS, 2.8-8.0+ months). Overall survival data were immature due to the limited observation period. A total of 8/16 patients (50%) had at least one grade 3 adverse event (AE), and 5 (31.3%) patients reported serious AEs. The most commonly reported AEs were diarrhea and stomatitis (37.5% each), platelet count decrease (31.3%), and anemia (25%). Overall, orally administered single agent ibrutinib was efficacious with an acceptable safety profile in Japanese patients with relapsed or refractory MCL. Clinical trial registration NCT02169180 (ClinicalTrials.gov).

  15. Pancreas volume reduction and metabolic effects in Japanese patients with severe obesity following laparoscopic sleeve gastrectomy.

    PubMed

    Umemura, Akira; Sasaki, Akira; Nitta, Hiroyuki; Baba, Shigeaki; Ando, Taro; Kajiwara, Takashi; Ishigaki, Yasushi

    2017-03-17

    This study aimed to assess the relationship between the metabolic effect after laparoscopic sleeve gastrectomy (LSG) in morbidly obese Japanese patients, with or without type 2 diabetes mellitus (T2DM), and improved pancreatic steatosis (PS). The study enrolled 27 morbidly obese Japanese patients who were undergoing LSG. Their clinical and metabolic effects were evaluated at baseline and six months after LSG. Pancreas volume (PV), pancreatic attenuation (PA), and splenic attenuation (SA) were measured using a 64-row computed tomography (CT). Changes in PV, PA-SA, and PA/SA were evaluated. The mean body-weight loss, body mass index loss, and percentage of excess weight loss (%EWL) were -34.4 kg (p < 0.001), -11.0 kg/m(2) (p < 0.001), and 43.7%, respectively. The mean PV was 96.7 mL at baseline, and it decreased six months after LSG (-16.3mL, p < 0.001). The mean PA significantly increased six months after LSG (9.5 HU, p < 0.001). PA-SA (-23.2 HU vs. -13.3 HU, p = 0.003), and PA/SA (0.54 vs. 0.73, p < 0.001) also significantly increased six months after LSG. In T2DM patients, decreased PV correlated with decreased fasting blood sugar, decreased insulin, and reduced liver volume. In conclusion, PV significantly decreased after LSG in morbidly obese Japanese patients, and that decrease correlated with improvements in PS. In addition, PS plays an important role of development and progression of insulin resistance and T2DM.

  16. Efficacy and Safety of Sitagliptin in Japanese Patients With Type 2 Diabetes

    PubMed Central

    Ohmura, Hirotoshi; Mita, Tomoya; Taneda, Yoshinobu; Sugawara, Masahiro; Funayama, Hideaki; Matsuoka, Joe; Watada, Hirotaka; Daida, Hiroyuki

    2015-01-01

    Background The aim of this study was to investigate the clinical efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes. Methods A total of 3,247 subjects treated with sitagliptin were retrospectively recruited. Glucose parameters were collected at baseline, and 1, 3 and 6 months after initiation of sitagliptin. In addition, we explored factors that can be used to predict sitagliptin-induced reduction in HbA1c using linear mixed effect model. Factors associated with hypoglycemic events were examined by logistic analyses. Results We analyzed the available data of 3,201 subjects (1,287 females). Treatment of sitagliptin significantly reduced HbA1c level from 7.44±1.20% at baseline to 6.73±0.99% at 6 months (P < 0.0001). Linear mixed effect model analyses demonstrated that reduction of HbA1c was associated with higher baseline HbA1c level, younger age, lower BMI and sitagliptin monotherapy. During this study, 82 cases of hypoglycemia were recorded. Logistic analyses indicated that hypoglycemic events were more frequent in female patients, and patients with low BMI, long history of type 2 diabetes, high HbA1c and on combination therapy experienced. Other adverse events were rare and mild. Conclusions Sitagliptin is effective for diabetic management and generally well tolerated in Japanese patients with type 2 diabetes. This trial was registered with UMIN (no. 000004121). PMID:25699116

  17. Multicenter study on caries risk assessment in Japanese adult patients.

    PubMed

    Arino, Masumi; Ataru, Ito; Fujiki, Shozo; Sugiyama, Seiichi; Hayashi, Mikako

    2015-10-01

    This study was conducted to identify significant risk factors for the onset and the accumulation of new caries in adult patients undergoing regular preventive therapy. The data of 732 patients from nine Japanese general dental practices were retrospectively analyzed. Classification and regression tree (CART) analysis was applied to develop a caries prediction model using the following patient parameters: age, number of teeth with caries experience (DMFT), levels of mutans streptococci (SM) and lactobacilli (LB), saliva flow rate and buffer capacity, and compliance with a preventive program. Poisson regression analysis was conducted to identify factors affecting caries accumulation within three years. CART analysis identified patients at high risk for primary caries with an odds ratio of 3.08 (95%CI, 1.55-5.79; p=0.0018) according to SM levels and compliance; and those for secondary caries with an odds ratio of 3.69 (95%CI, 2.29-5.91; p<0.0001) according to LB and SM levels. Poisson regression analyses showed that accumulation of primary caries was affected by compliance (p<0.001), SM (p<0.001) and LB (p=0.013). Accumulation of secondary caries was affected by DMFT (p<0.001), SM (p<0.001) and LB (p<0.001). CART is an important tool in identifying the risk of caries development in individual adult patients. Cariogenic bacteria are important factors for both the onset and accumulation of primary and secondary caries. Participation in a regular preventive program limits the onset and the accumulation of primary caries in adult patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Etiological Spectrum of Clinically Diagnosed Japanese Encephalitis Cases Reported in Guizhou Province, China, in 2006 ▿

    PubMed Central

    Xufang, Ye; Huanyu, Wang; Shihong, Fu; Xiaoyan, Gao; Shuye, Zhao; Chunting, Liu; Minghua, Li; Yougang, Zhai; Guodong, Liang

    2010-01-01

    The proportion of laboratory-confirmed Japanese encephalitis (JE) virus (JEV) infections was compared to the number of JE cases reported on the basis of seasonality and the clinical symptoms of hospitalized patients in Guizhou Province, China, between April and November 2006. Of the 1,837 patients with reported JE, 1,382 patients in nine prefectures were investigated. JE was confirmed in 1,210 of 1,382 (87.6%) patients by a JEV-specific immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA), heminested reverse transcriptase PCR, and virus isolation. Two strains of JEV belonging to genotype 1 were isolated. Other viral pathogens responsible for encephalitis, including echovirus, mumps virus, herpes simplex virus, and cytomegalovirus, were identified in 67 of 172 (38.9%) JE-negative cases. On the basis of the distribution of the laboratory-confirmed JE cases from different hospitals according to the Chinese administrative division, which included hospitals at the provincial, city, county, and township levels, county hospitals detected the highest number of JE cases (81.8%), whereas township hospitals detected the smallest number of JE cases (1.4%). Provincial and city hospitals had the highest and lowest rates of accuracy of providing a clinical diagnosis of JE, as confirmed by laboratory testing (91.8% and 76.7%, respectively). This study demonstrates that laboratory confirmation improves the accuracy of diagnosis of JE and that an enhanced laboratory capacity is critical for JE surveillance as well as the identification of other pathogens that cause encephalitic syndromes with clinical symptoms similar to those caused by JEV infection. PMID:20147638

  19. Gender differences of low-dose aspirin-associated gastroduodenal ulcer in Japanese patients

    PubMed Central

    Okada, Kazuhisa; Inamori, Masahiko; Imajyo, Kento; Chiba, Hideyuki; Nonaka, Takashi; Shiba, Tadahiko; Sakaguchi, Takashi; Atsukawa, Kazuhiko; Takahashi, Hisao; Hoshino, Etsuo; Nakajima, Atsushi

    2010-01-01

    AIM: To clarify the gender differences about the clinical features and risk factors of low-dose aspirin (LDA) (81-100 mg daily)-associated peptic ulcer in Japanese patients. METHODS: There were 453 patients under treatment with LDA (298 males, 155 females) who underwent esophagogastroduodenoscopy at the Department of Gastroenterology and Hepatology of Hiratsuka City Hospital between January 2003 and December 2007. They had kept taking the LDA or started treatment during the study period and kept taking LDA during the whole period of observation. Of these, 119 patients (87 males, 32 females) were diagnosed as having LDA-associated peptic ulcer. We examined the clinical factors associated with LDA-associated peptic ulcer in both sexes. RESULTS: A history of peptic ulcer was found to be the risk factor for LDA-associated peptic ulcer common to both sexes. In female patients, age greater than 70 years (prevalence ORs 8.441, 95% CI: 1.797-33.649, P = 0.0069) was found to be another significant risk factor, and the time to diagnosis as having LDA-associated peptic ulcer by endoscopy was significantly shorter than that in the male patients (P = 0.0050). CONCLUSION: We demonstrated gender differences about the clinical features and risk factors of LDA-associated peptic ulcer. Special attention should be paid to aged female patients taking LDA. PMID:20397269

  20. Physician-patient communication and patient satisfaction in Japanese cancer consultations.

    PubMed

    Ishikawa, Hirono; Takayama, Tomoko; Yamazaki, Yoshihiko; Seki, Yukiko; Katsumata, Noriyuki

    2002-07-01

    Over the past few decades, physician-patient communication has been intensively studied in western countries, because of its importance for the physician-patient relationship and patient health outcomes. Although various concepts and models of this relationship have recently been introduced in Japan, there are few studies on Japanese physician-patient interaction. The purpose of this study is to describe characteristics of physician-patient communication in a Japanese cancer consultation, and to examine the relation of this interaction with patient satisfaction. One hundred and forty cancer outpatients and twelve physicians were included. The Roter Interaction Analysis System (RIAS), one of the most frequently used systems for analyzing physician-patient interaction, was applied, physicians made more utterances directing the interaction than patients did, and their discussion was largely focused on biomedical topics. It can be concluded that the structure of the physician-patient interaction in our study was basically similar to those in previous western studies, although some differences were also found. The relation between physician-patient communication and patient satisfaction was generally consistent with previous studies. Patients were more satisfied with consultations in which the physician used more open-ended questions. On the other hand, physician direction and encouragement was negatively associated with patient satisfaction. Also, patients who asked more questions were less satisfied with the consultation.

  1. Distribution and annual changes in Streptococcus pneumoniae serotypes in adult Japanese patients with pneumonia.

    PubMed

    Akata, Kentaro; Chang, Bin; Yatera, Kazuhiro; Kawanami, Toshinori; Yamasaki, Kei; Naito, Keisuke; Noguchi, Shingo; Ishimoto, Hiroshi; Mukae, Hiroshi

    2015-10-01

    Streptococcus pneumoniae is one of the main causative bacteria in patients with pneumonia; however, there are no data regarding serotype changes in adult patients with pneumonia after the introduction of the pneumococcal vaccine (PCV7) for childhood immunization in Japan. We herein evaluated the serotype distribution in adult patients with pneumonia. This retrospective epidemiological study was performed at the University of Occupational and Environmental Health, Japan from January 2011 to December 2013. The serotypes of pneumococcal isolates obtained from patients with pneumonia were evaluated along with the patients' clinical information. A total of 81 patients with pneumococcal pneumonia (89 episodes) from whom S. pneumoniae was isolated were included. The numbers (percentages) of sample types were as follows: sputum 55 (61.8%), intratracheal tube suction 15 (16.9%), intrabronchial sampling 5 (5.6%) and bronchoalveolar lavage fluid 14 (15.7%). The PCV7 serotypes decreased significantly among the patients with pneumococcal pneumonia from 46.4% in 2011 to 20.0% in 2013 (p < 0.05). Conversely, PCV13 and 23-valent pneumococcal polysaccharide vaccination (PPSV23) serotypes other than PCV7 serotypes mildly increased during this period. In addition, the frequency of serotypes 19F, 23F and 4 (which are covered by PCV7) decreased annually; however, the changes in the frequencies of the other serotypes were not significant. This study demonstrated the yearly decrease of PCV7 serotypes in adult pneumococcal pneumonia patients after introducing PCV7 into the childhood immunization schedule in Japan. Continued surveillance of pneumococcal serotype changes is important for the proper use of different pneumococcal vaccines. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Primary care patient experience and cancer screening uptake among women: an exploratory cross-sectional study in a Japanese population.

    PubMed

    Aoki, Takuya; Inoue, Machiko

    2017-01-01

    Patient experience and clinical quality, which are represented by preventive care measures such as cancer screening, are both widely used for the evaluation of primary care quality. The aim of this study was to examine the association between patient experience and cancer screening uptake among women in a Japanese population. We conducted a cross-sectional mail survey. The questionnaire was sent to 1000 adult female residents randomly selected from a basic resident register in Yugawara town, Kanagawa, Japan. We assessed patient experience of primary care using a Japanese version of Primary Care Assessment Tool (JPCAT) and uptake of breast and cervical cancer screening. The overall response rate was 46.5%. Data were analyzed for 190 female participants aged 21-74 years who had a usual source of primary care. Multivariate logistic regression analyses revealed that the JPCAT total score was significantly associated with uptake of breast cancer screening [odds ratio (OR) per 1 standard deviation increase = 1.63; 95% CI 1.11-2.41], but not with uptake of cervical cancer screening (OR per 1 standard deviation increase = 1.47; 95% CI 0.97-2.24). Patient experience of primary care was associated with uptake of breast cancer screening among Japanese women. The results of our study might support the argument that patient experience of primary care and the clinical process of preventive care, such as breast cancer screening, are linked.

  3. Cefotiam disposition in markedly obese athlete patients, Japanese sumo wrestlers.

    PubMed Central

    Chiba, K; Tsuchiya, M; Kato, J; Ochi, K; Kawa, Z; Ishizaki, T

    1989-01-01

    Markedly obese athletes like Japanese sumo wrestlers may frequently suffer various traumas which result in the prophylaxis or treatment of posttraumatic infection with antibiotics. However, appropriate dosage regimens in this group of patients have not been fully known for many antibiotics. Therefore, we studied the kinetic disposition of cefotiam, a parenteral, broad-spectrum cephalosporin with activity against gram-positive and -negative bacteria, after an intravenous dose (2 g) infused over 30 min into 15 sumo wrestler patients with an excess body weight (130 to 220% of ideal body weight) and 10 control patients with a normal weight (90 to 102% of ideal body weight). Mean (+/- standard deviation) clearance and steady-state volume of distribution were significantly greater in the sumo wrestler than in the control group (38.3 +/- 9.4 versus 23.5 +/- 6.0 liters/h, P less than 0.001, and 30.2 +/- 8.0 versus 17.9 +/- 6.1 liters, P less than 0.001). Mean elimination half-life was slightly but significantly longer in the sumo wrestler than in the control group (0.91 +/- 0.14 versus 0.74 +/- 0.20 h, P less than 0.05). However, mean residence time did not differ between the two groups (0.79 +/- 0.10 versus 0.75 +/- 0.14 h). The statistical differences in clearance and volume of distribution between the two groups disappeared when these kinetic parameters were corrected for body surface area, but not for total body weight or ideal body weight. The results suggest that the dosage calculation of cefotiam, a hydrophilic antibiotic, should be made on the basis of body surface area in morbidly obese athlete or sumo wrestler patients. However, whether this recommendation should extend to other nonathlete obese subjects remains to be determined. PMID:2802548

  4. [Incidence and clinical characteristics of perioperative pulmonary thromboembolism in Japan in 2008--results from the annual study of Japanese Society of Anesthesiologists, Committee on Patient Safety and Risk Management, Perioperative Pulmonary Thromboembolism Working Group].

    PubMed

    Kuroiwa, Masayuki; Furuya, Hitoshi; Seo, Norimasa; Kitaguchi, Kastuyasu; Nakamura, Mashio; Sakuma, Masahito; Chuma, Riichiro

    2010-05-01

    The Japanese Society of Anesthesiologists (JSA) has maintained records of the annual incidence and characteristics of perioperative pulmonary thromboembolism (perioperative PTE) since 2002. The aim of this paper was to provide recent results of the JSA annual study conducted in 2008, and to determine the current factors that tend to prevent perioperative venous thromboembolism (VTE) in Japan. A comprehensive questionnaire designed by the JSA PTE working group was mailed to all institutions certified as teaching hospitals by JSA. The data tics of patients with perioperative PTE, such as types of diseases and surgeries, age, sex, methods used for the prevention of VTE (in some cases), and prognosis of perioperative PTE. The rate of effective responses was 56.1% (634/1116), and 1,177,626 surgeries were registered during the study period. There were 324 patients who were reported to have had PTE, and the incidence was 2.75 per 10,000 surgeries. The incidence of perioperative PTE in 2008 did not change significantly from that in 2005-07. The surgeries that most commonly resulted in perioperative PTE were limb and/or hip joint surgery (5.71 per 10,000 surgeries), craniotomy (4.64 per 10,000), and thoracotomy with laparotomy (3.46 per 10,000 surgeries). The mortality rate of perioperative PTE in 2008 was found to have significantly decreased from that in 2005-07 (15.6% vs. 22.4%; P = 0.01). Further, the rate of patients who received anticoagulant drugs in 2008 was significantly higher than that in 2005-07 (17.6% vs. 10.8%; P = 0.0018). Individual guidelines for the prevention of perioperative VTE were adopted in 55.4% of the training institutions. The increase in the percentage of patients who received anticoagulant drugs around the time of the operation, and the decreased mortality of patients with perioperative PTE suggested that the prophylaxis for perioperative VTE with anticoagulant drugs reduces perioperative mortality.

  5. Acoustic characteristics of ataxic speech in Japanese patients with spinocerebellar degeneration (SCD).

    PubMed

    Ikui, Yukiko; Tsukuda, Mamoru; Kuroiwa, Yoshiyuki; Koyano, Shigeru; Hirose, Hajime; Taguchi, Takahide

    2012-01-01

    In English- and German-speaking countries, ataxic speech is often described as showing scanning based on acoustic impressions. Although the term 'scanning' is generally considered to represent abnormal speech features including prosodic excess or insufficiency, any precise acoustic analysis of ataxic speech has not been performed in Japanese-speaking patients. This raises the question of what is the most dominant acoustic characteristic of ataxic speech in Japanese subjects, particularly related to the perceptual impression of 'scanning'. The study was designed to investigate the nature of speech characteristics of Japanese ataxic subjects, particularly 'scanning', by means of acoustic analysis. The study comprised 20 Japanese cases with spinocerebellar degeneration diagnosed to have a perceptual impression of scanning by neurologists (ataxic group) and 20 age-matched normal healthy subjects (control group). Recordings of speech samples of Japanese test sentences were obtained from each subject. The recorded and digitized acoustic samples were analysed using 'Acoustic Core-8' (Arcadia Inc.). Sentence duration was significantly longer in the ataxic group as compared with the control group, indicating that the speaking rate was slower in the ataxic subjects. Segment duration remained consistent in both vowels and consonants in the control group as compared with the ataxic group. In particular, the duration of vowel segments, i.e. the nucleus of Japanese mora, was significantly invariable in the control group regardless of differences between subjects as well as in segments compared with the ataxic group. In addition, the duration of phonemically long Japanese vowels was significantly shorter in the ataxic group. The results indicate that the perceptual impression of 'scanning' in Japanese ataxic cases derives mainly from the breakdown of isochrony in terms of difficulty in keeping the length of vowel segments of Japanese invariable during speech production. In

  6. Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome.

    PubMed

    Minami, M; Urano, Y; Ishigami, T; Tsuda, H; Kusaka, J; Arase, S

    2001-09-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental and skeletal anomalies, palmo-plantar pits, odontogenic keratocysts, ectopic calcification, and occurrence of various types of tumors including basal cell carcinoma. Recent evidence has indicated that the human homologue of a Drosophila segment polarity gene, PTCH, is a NBCCS susceptibility gene. In the study presented here, we detected two novel mutations of the PTCH gene, I805X/2395delC and Y93X/C297A, in two unrelated Japanese patients. Early protection of the skin from the sunlight is important to the prevention of BCC development in NBCCS patients. Genetic analysis of the PTCH gene is essential for the early, definitive diagnosis of NBCCS, especially before the expression of clinical manifestations is complete.

  7. [Proposal for improving EQA programs in clinical microbiology by the Japanese Association of Medical Technologists].

    PubMed

    Inuzuka, Kazuhisa

    2005-04-01

    External quality assessment (EQA) programs have been conducted by the Japanese Association of Medical Technologists (JAMT) since 1989. The nationwide EQA programs have provided feedback for improving clinical tests quality in individual laboratories. The participating laboratories have been expected to process the survey samples according to their usual practice for patient specimens. However, many problems relating to the EQA programs in clinical microbiology have been raised. Dishonesty in the responses, survey samples being handled in a manner that improves assessment results, surveys depending on volunteers because of time and cost limitations were some of the initial problems. In addition, the criteria used to evaluate the results were poorly understood, so that neither examiners not participants were clear as to how the evaluation worked. And finally, the nationwide EQA programs can detect only gross errors and use invalid methods for evaluating routine performances. They have been measuring only a few steps in specimens processing. To assess overall laboratory competence, other methods are needed. It is time to reform the JAMT nationwide EQA program to initiate real proficiency testing and to this end it is necessary to increase collaboration between JAMT and the regional associations of medical technologists, so that the improved testing program can be properly administered.

  8. Validation of predictive equations for resting energy expenditure in Japanese pediatric Crohn's disease patients: preliminary study.

    PubMed

    Arai, Katsuhiro; Funayama, Rie; Takahashi, Mieko; Sakai, Rie; Shimizu, Hirotaka; Obayashi, Naho; Matsui, Akira

    2015-04-01

    Predictive equations are often used to estimate resting energy expenditure (REE). Determining the appropriate equation for different patient types, however, remains inconclusive, as in the case of Japanese children with Crohn's disease (CD). The aim of this study was to identify an appropriate predictive equation for measuring REE in Japanese children with CD. Twelve Japanese children with CD managed at the National Center for Child Health and Development in Tokyo, Japan, were studied. REE (kcal/day) was measured using indirect calorimetry. The predictive equations used were the Japanese Dietary Reference Intakes (2010), the Schofield equation, the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU) equation and the Cunningham equation. Difference between predicted and measured REE was analyzed on Bland-Altman plot. Japanese Dietary Reference Intakes (2010) had the smallest difference between predicted and measured REE. Weight was the primary predictor of REE on multiple regression analysis. As well, Japanese Dietary Reference Intakes (2010) had the highest ratio of weight to predicted REE (98.5%). Of the four equations, Japanese Dietary Reference Intakes (2010) appeared to be the most practical and accurate predictive equation for REE in Japanese children with CD. © 2014 Japan Pediatric Society.

  9. Phase-1 study of abiraterone acetate in chemotherapy-naïve Japanese patients with castration-resistant prostate cancer.

    PubMed

    Matsubara, Nobuaki; Uemura, Hiroji; Fukui, Iwao; Niwakawa, Masashi; Yamaguchi, Akito; Iizuka, Koho; Akaza, Hideyuki

    2014-10-01

    Persistent androgen synthesis under castration status in adrenal gland, testes and tumor cells is thought to be one of the major causes of development and progression of castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA), the prodrug of abiraterone, which is an inhibitor of androgen synthesis enzymes, was evaluated for pharmacokinetics, pharmacodynamics, preliminary efficacy and safety in Japanese patients with CRPC in a phase-1, open-label and dose-escalation study. Chemotherapy-naïve Japanese CRPC patients (N = 27) received one of four AA daily doses (250 mg [n = 9], 500 mg [n = 6], 1000 [1 h premeal] mg [n = 6] and 1000 [2 h postmeal] mg [n = 6]) continuously through 28-day treatment cycles. In the first cycle, AA monotherapy was given on days 1-7 for pharmacokinetics, and AA plus prednisone (5 mg twice daily) from days 8 to 28. Of 27 patients, 9 continued treatment with AA until the data cut-off date (18 July 2013). Over the evaluated dose range, plasma abiraterone concentrations increased with dose, with median tmax 2-3 h. At each dose level, mean serum corticosterone concentrations increased, while testosterone and dehydroepiandrosterone sulfate concentrations rapidly decreased following a single AA dose and were further reduced to near the quantification limit on day 8 regardless of the dose. At least 3 patients from each dose-group experienced ≥50% prostate-specific antigen reduction, suggesting clinical benefit from AA in Japanese CRPC patients. AA was generally well-tolerated, and, therefore, the recommended AA dosage regimen in Japanese CRPC patients is 1000 mg oral dose under modified fasting conditions (at least 1 h premeal or 2 h postmeal). This study is registered at ClinicalTrials.gov: NCT01186484.

  10. Can we determine depressive conditions on the basis of somatic symptoms? A cross-sectional study of depressive conditions among Japanese patients at a university hospital general medicine clinic.

    PubMed

    Aoki, Akiko; Nagate, Motoyoshi; Utsumi, Kenta; Tanaka, Asashi; Inoue, Yuichi; Otaki, Junji; Shimbo, Takuro; Ashizawa, Tatsuto

    2012-01-01

    We evaluated the relationship between somatic symptoms and depressive conditions among patients visiting the general medicine clinic of a university hospital. We distributed interview forms to 332 consecutive patients who visited our clinic for the first time between March and July 2011. Somatic symptoms were rated using a symptom checklist, and depressive conditions were evaluated using the Zung Self-Rating Depression Scale (SDS). We categorized and compared 2 groups of patients: patients with an SDS score of more than 48 (depressive group) and patients with an SDS score of less than 48 (non-depressive group). A total of 284 (85.5%) patients returned the forms. The SDS scores were obtained from the forms of 182 patients (64.1%). The average age of these 182 patients was 46.5±18.04 years. The mean number of checked symptoms was 4.3±3.03, and the most common symptom was general fatigue (n=106; 58.2%). The number of checked symptoms in the survey was higher in the depressive group patients than in the non-depressive group patients. Multiple logistic regression analysis indicated that general fatigue, headache, and sleeping problems were significant dependent variables which were related to depressive conditions. We defined these 3 symptoms as depression-related somatic symptoms (DRSS). On a receiver-operating characteristic curve, the optimal cutoff scores were 2 of 3 DRSS and 4 of 20 somatic symptoms. General physicians should consider possible depressive conditions when patients have 2 or more DRSS or 4 or more somatic symptoms.

  11. Clinical Characteristics of Stenotrophomonas maltophilia Bacteremia: A Regional Report and a Review of a Japanese Case Series

    PubMed Central

    Ebara, Hirotaka; Hagiya, Hideharu; Haruki, Yuto; Kondo, Eisei; Otsuka, Fumio

    2017-01-01

    Objective Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes fatal infections in critically ill or immunocompromised patients. S. maltophilia bacteremia (SMB) is a rare condition, and its clinical characteristics in Japanese settings are not well known. Methods The medical charts of patients with SMB were retrospectively reviewed at two medical facilities (Okayama University Hospital and Tsuyama Chuo Hospital) for seven years. The data were analyzed along with those previously reported from other Japanese facilities. Result A total of 181 patients (110 men and 71 women) were evaluated. The major underlying diseases included hematologic malignancy (36.5%), solid organ malignancy (25.4%), and neutropenia (31.5%). The recent use of carbapenem was seen in 56.9% of the cases in total, and more than one-third of the patients in our hospitals were treated with carbapenem at the onset of SMB. Of 28 (63.6%) of 44 cases treated for S. maltophilia, those who did not survive were more likely to have been treated with broad-spectrum antibiotics. A multivariate analysis revealed that a higher updated Charlson Comorbidity Index [odds ratio (95% confidence interval), 1.75 (1.11-2.75); p=0.015] and intubation [odds ratio (95% confidence interval), 12.6 (1.62-97.9); p=0.016] were associated with mortality in our cases. Pathogens were often resistant to ceftazidime but susceptible to minocycline, trimethoprim/sulfamethoxazole, and fluoroquinolones. The overall mortality rates within 30 and 90 days were 37.5% and 62.5%, respectively. Conclusion The clinical characteristics of SMB in Japanese cases were similar to those reported from other countries. Clinicians should be aware that breakthrough infection by S. maltophilia may occur during administration of carbapenem. PMID:28090041

  12. Anti-Malassezia-Specific IgE Antibodies Production in Japanese Patients with Head and Neck Atopic Dermatitis: Relationship between the Level of Specific IgE Antibody and the Colonization Frequency of Cutaneous Malassezia Species and Clinical Severity

    PubMed Central

    Zhang, Enshi; Tanaka, Takafumi; Tajima, Mami; Tsuboi, Ryoji; Kato, Hiroshi; Nishikawa, Akemi; Sugita, Takashi

    2011-01-01

    Atopic dermatitis of the head and neck (HNAD) is recognized as a separate condition. Malassezia, the predominant skin microbiota fungus, is considered to exacerbate atopic dermatitis (AD), especially HNAD. In the present study, we investigated the relationships between the levels of specific IgE antibodies, colonization frequency of eight predominant Malassezia species, and clinical severity in 61 patients with HNAD (26 mild, 24 moderate, and 11 severe cases). As clinical severity increased, the levels of specific IgE antibodies against eight Malassezia species also increased. Species diversity of the Malassezia microbiota in scale samples from patients was analyzed by nested PCR using species-specific primers. The clinical severity of HNAD was correlated with the total level of specific IgE antibodies against Malassezia species and the number of Malassezia species detected. PMID:22253636

  13. Helicobacter pylori infection and gastropathy: A comparison between Indonesian and Japanese patients

    PubMed Central

    Abdullah, Murdani; Ohtsuka, Hiroyuki; Rani, Abdul Aziz; Sato, Tadashi; Syam, Ari F; Fujino, Masayuki A

    2009-01-01

    AIM: To compare the effects of Helicobacter pylori (H pylori) infection on gastropathy between Indonesian and Japanese patients. METHODS: Biopsy specimens were obtained during upper gastrointestinal endoscopy from 167 subjects (125 Indonesians and 42 Japanese) with uninvestigated symptoms of dyspepsia. The specimens were analyzed for the presence of H pylori using urease analysis, histopathology, and cell culture. The grade and activity of gastritis was assessed using the updated Sydney system. RESULTS: The percentages of Indonesian and Japanese patients who were H pylori-positive at the antrum or body of the stomach were similar (68% and 59.5%, respectively; P = 0.316). Of those who were H pylori-positive, more Japanese patients than Indonesian patients had high levels of polymorphonuclear cells (P = 0.001), mononuclear cells (P = 0.013), glandular atrophy (P = 0.000), and intestinal metaplasia (P = 0.011) in both the antrum and body of the stomach. CONCLUSION: The grade of gastritis and prevalence of mucosal atrophy and intestinal metaplasia were higher in Japanese patients. The difference between Indonesian and Japanese patients was significant. PMID:19842224

  14. Population pharmacokinetics of erlotinib in Japanese patients with advanced non-small cell lung cancer.

    PubMed

    Emoto-Yamamoto, Y; Iida, S; Kawanishi, T; Fukuoka, M

    2015-04-01

    This study aimed to elucidate the pharmacokinetics of erlotinib in Japanese patients with advanced non-small cell lung cancer (NSCLC) and to investigate the relationship between erlotinib exposure and the occurrence of interstitial lung disease (ILD)-like events. Population pharmacokinetics analysis was performed using nonlinear mixed-effects modelling software (NONMEM) based on 348 plasma samples from 97 patients obtained in two phase II clinical studies. Individual empirical Bayesian estimates (EBEs) of apparent oral clearance (CL/F) and Cmax were compared between the patients who developed and did not develop ILD-like events. A 1-compartment model with first-order absorption and first-order elimination was used to describe the plasma concentrations of erlotinib. The estimated population pharmacokinetics parameters were as follows: 4·71 L/h for CL/F, 163 L for apparent volume of distribution (Vc /F) and 1·97 h(-1) for absorption rate constant (Ka ). Total bilirubin (TBIL) and alpha 1-acid glycoprotein (AGP) were identified as statistically significant covariates for CL/F. No differences in CL/F and Cmax were observed between the patients with ILD-like events and those without ILD-like events. A population pharmacokinetics model of erlotinib was developed and validated in Japanese patients. There was no relationship between exposure of erlotinib before the occurrence of ILD-like events and the occurrence of ILD-like events when erlotinib was administered at the same dosage. The high plasma concentration of erlotinib reported in patients after the onset of ILD-like events may be explained by CL/F decrease which occurs along with increasing levels of AGP which was identified as a covariate for CL/F. © 2014 John Wiley & Sons Ltd.

  15. Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3-methoxy-4-hydroxyphenylglycol and homovanillic acid in Japanese patients with major depressive disorder

    PubMed Central

    Atake, Kiyokazu; Yoshimura, Reiji; Hori, Hikaru; Katsuki, Asuka; Nakamura, Jun

    2015-01-01

    Purpose This study investigated the relationships among the plasma levels of catecholamine metabolites, the clinical response to duloxetine treatment, and Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene. Subjects and methods Sixty-four patients and 30 healthy control subjects were recruited. Major depressive episodes were diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. The severity of depression was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD17). Patients whose HAMD17 scores were 15 or greater were enrolled in the study. Blood sampling and clinical evaluation were performed at week 0 and week 8. The levels of plasma catecholamine metabolites were measured using high-performance liquid chromatography with electrochemical detection. Genotyping was performed using direct sequencing. Results Thirty of 45 patients (67%) responded to duloxetine treatment during the 8 weeks of treatment. The baseline plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), but not homovanillic acid (HVA), were lower in patients with major depressive disorder (MDD) who had the Val/Val genotype than in patients who were Met-carriers. Patients with MDD and the Val/Val genotype, but not Met carriers, had increased plasma levels of MHPG after 8 weeks of duloxetine treatment. The baseline plasma MHPG levels in healthy control subjects with the Val/Val genotype were significantly higher than those in patients with MDD. Among the subjects in the MDD group with the Val/Val genotype, the plasma MHPG levels increased to the same degree as in the healthy control subjects with the Val/Val genotype after 8 weeks of duloxetine treatment. Conclusion The relationship among the COMT Val158Met polymorphism, plasma levels of catecholamine metabolites, and responses to duloxetine is complex. Nevertheless, our results suggest that patients with MDD and the

  16. Japanese Encephalitis—A Pathological and Clinical Perspective

    PubMed Central

    Ghosh, Debapriya; Basu, Anirban

    2009-01-01

    Japanese encephalitis (JE) is the leading form of viral encephalitis in Asia. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. JEV is endemic to many parts of Asia, where periodic outbreaks take hundreds of lives. Despite the catastrophes it causes, JE has remained a tropical disease uncommon in the West. With rapid globalization and climatic shift, JEV has started to emerge in areas where the threat was previously unknown. Scientific evidence predicts that JEV will soon become a global pathogen and cause of worldwide pandemics. Although some research documents JEV pathogenesis and drug discovery, worldwide awareness of the need for extensive research to deal with JE is still lacking. This review focuses on the exigency of developing a worldwide effort to acknowledge the prime importance of performing an extensive study of this thus far neglected tropical viral disease. This review also outlines the pathogenesis, the scientific efforts channeled into develop a therapy, and the outlook for a possible future breakthrough addressing this killer disease. PMID:19787040

  17. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

    PubMed

    Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

    2012-01-01

    The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

  18. Diabetes mellitus after kidney transplantation in Japanese patients: The Japan Academic Consortium of Kidney Transplantation study.

    PubMed

    Okumi, Masayoshi; Unagami, Kohei; Hirai, Toshihito; Shimizu, Tomokazu; Ishida, Hideki; Tanabe, Kazunari

    2017-03-01

    To clarify the incidence rate of post-transplant diabetes mellitus and associated risk factors in Japanese kidney transplant recipients, and to explore which treatment components are most effective in reducing post-transplant diabetes mellitus. We analyzed 849 Japanese non-diabetic adult recipients who had undergone living kidney transplantation and had received tacrolimus-based immunosuppression from 1996 to 2013 with a median follow-up of 5 years. In all, 127 patients developed post-transplant diabetes mellitus during the follow-up period. The incidence rate of post-transplant diabetes mellitus was 15.1% (95% confidence interval 12.7-17.5) at 5 years. Recipient age (hazard ratio 1.05, 95% confidence interval 1.05-1.06, P < 0.001 for every 5-year increase), obesity (hazard ratio 1.70, 95% confidence interval 1.06-2.73, P = 0.028), tacrolimus trough level at 2 weeks post-transplantation (hazard ratio 1.06, 95% confidence interval 1.03-1.09, P < 0.001 for a 1-ng/mL increase) and mycophenolate mofetil use (hazard ratio 0.46, 95% confidence interval 0.28-0.77, P = 0.003) were significant predictors of post-transplant diabetes mellitus. Estimated 5-year predicted incidence rate after adjusting for age and obesity was 9.4% for recipients with a low tacrolimus trough level, and receiving mycophenolate mofetil and 38.4% for recipients with a high tacrolimus trough level and not receiving mycophenolate mofetil. Post-transplant diabetes mellitus is a common complication in Japan, similar to that in other Western countries. The present results show that an appropriate immunosuppressive regimen with a combination of tacrolimus and mycophenolate mofetil can reduce the likelihood of developing post-transplant diabetes mellitus. Clinical trials are required to confirm these findings. © 2016 The Japanese Urological Association.

  19. High Rates of Native Hawaiian and Older Japanese Patients Hospitalized with Dementia in Hawai'i

    PubMed Central

    Sentell, Tetine L.; Valcour, Nicole; Ahn, Hyeong Jun; Miyamura, Jill; Nakamoto, Beau; Chow, Dominic; Masaki, Kamal; Seto, Todd B.; Chen, John J.; Shikuma, Cecilia

    2014-01-01

    Limited data exist on dementia in Native Hawaiians and many Asian subgroups in the United States. Inpatients with dementia have higher costs, longer stays, and higher mortality compared to those without dementia. This study compared the rates of inpatients with a dementia diagnosis for disaggregated Asian and Pacific Islanders (Native Hawaiian, Chinese, Japanese, Filipino) vs. White by age group (18-59, 60-69, 70-79, 80-89 and 90+ years) for all adult patients hospitalized in Hawai'i between December 2006 and December 2010. A total of 13,465 in patients with a dementia diagnosis were identified by ICD-9 codes. Rates were calculated using population size denominators derived from the US Census. Across all age categories, Native Hawaiians had the highest unadjusted rates of inpatients with dementia and were hospitalized with a dementia diagnosis at younger ages than other racial/ethnic groups. In adjusted models compared to Whites (controlling for gender, residence location, and insurer), Native Hawaiians had significantly higher rates of inpatients with dementia among those 18-59 years (aRR:1.50;95%CI:0.84-2.69), 60-69 years (aRR:2.53;95%CI:1.74-3.68), 70-79 years(aRR:2.19;95%CI:1.78-2.69) and 80-89 years (aRR:2.53;95%CI:1.24-1.71) as did Japanese aged 70-79 years (aRR:1.30;95%CI:1.01-1.67), 80-89 years (aRR:1.29;95%CI:1.05-1.57) and 90+ years (aRR:1.51;95%CI:1.24-1.85). Japanese aged 18-59 years had significantly lower rates than Whites (aRR:0.40; 95%CI:0.17-0.94).These patterns have important public health and clinical care implications for Native Hawaiians and older Japanese populations. Future studies should consider if preventable medical risk, care giving, socio-economic conditions, genetic disposition, or a combination of these factors are responsible for these findings. PMID:25537987

  20. TERT promoter mutations are rare in bone and soft tissue sarcomas of Japanese patients.

    PubMed

    Saito, Tsuyoshi; Akaike, Keisuke; Kurisaki-Arakawa, Aiko; Toda-Ishii, Midori; Mukaihara, Kenta; Suehara, Yoshiyuki; Takagi, Tatsuya; Kaneko, Kazuo; Yao, Takashi

    2016-01-01

    Recurrent hot-spot mutations in the telomerase reverse transcriptase (TERT) promoter have been reported in various types of tumor. In several tumor types, TERT promoter mutations are associated with poor clinical outcomes. TERT promoter mutations are reported to be rare in soft tissue tumors, with the exception of myxoid liposarcoma (MLS). Our previous study reported that TERT promoter mutations occurred in a subset of solitary fibrous tumors (SFTs) and were associated with adverse clinical outcomes in Japanese individuals. The site-specific frequency (e.g. central nervous or soft tissue origin) of TERT promoter mutations in our SFT cases appeared to be different from previously reported values in a European population. These findings prompted the present study to elucidate the potential role of ethnic background in the different frequencies of TERT promoter mutations in bone and soft tissue sarcomas. In the present study, TERT promoter mutations were examined in 180 cases of bone and soft tissue sarcomas. TERT promoter region mutations were identified in 10 cases [5 SFTs, 3 MLSs, 1 undifferentiated pleomorphic sarcoma (UPS) and 1 malignant granular cell tumor]. All mutations were C228T. The frequencies of TERT promoter mutation in MLS and UPS were 23.1 (3/13) and 5% (1/20), respectively. Only 1/5 patients with TERT-mutated tumors experienced local recurrence or distant metastasis. The present study revealed the first case of a malignant granular cell tumor with a TERT promoter mutation and revealed that the frequency of TERT promoter mutations in MLSs of Japanese patients is lower compared with that reported in German patients, providing evidence of a possible ethnic difference in the frequency of TERT promoter mutations.

  1. [Efficacy and safety of sugammadex (Org 25969) in reversing deep neuromuscular block induced by rocuronium or vecuronium in Japanese patients].

    PubMed

    Takeda, Junzo; Iwasaki, Hiroshi; Otagiri, Tetsutaro; Katoh, Takasumi; Shingu, Koh; Obara, Hidefumi; Nakatsuka, Hideki; Tomiyama, Yoshinobu; Kasaba, Toshiharu

    2014-10-01

    Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. We studied 99 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional dose of rocuronium or vecuronium for maintenance of deep block. At 1-2 PTC, 0.5-8.0 mg . kg-1 of sugammadex was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 66.9 min in the sugammadex 0.5 mg kg-1 group to 1.3 min in the sugammadex 8.0 mg kg-1 group. For the vecuronium-induced neuromuscular block it decreased from 79.5 min in the sugammadex 0.5 mg . kg-1 group to 2.9 min in the sugammadex 8.0 mg . kg-1 group. No clinical evidence of recurarization or residual curarization was observed. The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.

  2. Prevalence and risk factors for peri-implant diseases in Japanese adult dental patients.

    PubMed

    Ogata, Yorimasa; Nakayama, Yohei; Tatsumi, Junichi; Kubota, Takehiko; Sato, Shuichi; Nishida, Tetsuya; Takeuchi, Yasuo; Onitsuka, Tokuya; Sakagami, Ryuji; Nozaki, Takenori; Murakami, Shinya; Matsubara, Naritoshi; Tanaka, Maki; Yoshino, Toshiaki; Ota, Junya; Nakagawa, Taneaki; Ishihara, Yuichi; Ito, Taichi; Saito, Atsushi; Yamaki, Keiko; Matsuzaki, Etsuko; Hidaka, Toshirou; Sasaki, Daisuke; Yaegashi, Takashi; Yasuda, Tadashi; Shibutani, Toshiaki; Noguchi, Kazuyuki; Araki, Hisao; Ikumi, Noriharu; Aoyama, Yukihiko; Kogai, Hideki; Nemoto, Kenji; Deguchi, Shinji; Takiguchi, Takashi; Yamamoto, Matsuo; Inokuchi, Keita; Ito, Takatoshi; Kado, Takashi; Furuichi, Yasushi; Kanazashi, Mikimoto; Gomi, Kazuhiro; Takagi, Yukie; Kubokawa, Keita; Yoshinari, Nobuo; Hasegawa, Yoshiaki; Hirose, Tetsushi; Sase, Toshinaga; Arita, Hirokazu; Kodama, Toshiro; Shin, Kitetsu; Izumi, Yuichi; Yoshie, Hiromasa

    2017-03-31

    We investigated the prevalences and risk factors for peri-implant diseases in Japanese adult dental patients attending a follow-up visit at dental hospitals or clinics as part of their maintenance program. This cross-sectional multicenter study enrolled patients with dental implants who attended regular check-ups as part of a periodontal maintenance program during the period from October 2012 through September 2013. Patients with implants with at least 3 years of loading time were included in the study. The condition of peri-implant tissue was examined and classified into the following categories: healthy, peri-implant mucositis, and peri-implantitis. Patients were also evaluated for implant risk factors. A total of 267 patients (110 men, 157 women; mean age: 62.5 ± 10.7 years) were analyzed. The prevalence of patient-based peri-implant mucositis was 33.3% (n = 89), and the prevalence of peri-implantitis was 9.7% (n = 26). Poor oral hygiene and a history of periodontitis were strong risk factors for peri-implant disease. The present prevalences were lower than those previously reported. The quality of periodontal therapy before and after implant installation and patient compliance and motivation, as indicated by plaque control level, appear to be important in maintaining peri-implant tissue health.

  3. Prevalence of low-penetrant germline TP53 D49H mutation in Japanese cancer patients.

    PubMed

    Yamaguchi, Ken; Urakami, Kenichi; Nagashima, Takeshi; Shimoda, Yuji; Ohnami, Shumpei; Ohnami, Sumiko; Ohshima, Keiichi; Mochizuki, Tohru; Hatakeyama, Keiichi; Serizawa, Masakuni; Akiyama, Yasuto; Maruyama, Kouji; Katagiri, Hirohisa; Ishida, Yuji; Takahashi, Kaoru; Nishimura, Seiichiro; Terashima, Masanori; Kawamura, Taiichi; Kinugasa, Yusuke; Yamakawa, Yushi; Onitsuka, Tetsuro; Ohde, Yasuhisa; Sugino, Takashi; Ito, Ichiro; Matsubayashi, Hiroyuki; Horiuchi, Yasue; Mizuguchi, Maki; Yamazaki, Mutsumi; Inoue, Kengo; Wakamatsu, Kimiko; Sugiyama, Misato; Uesaka, Katsuhiko; Kusuhara, Masatoshi

    2016-01-01

    Using whole exome sequencing data obtained from 1,685 Japanese cancer patients, we examined genetic variations of germline TP53 and found 10 types of non-synonymous single nucleotide variants. In the present study, we focused on 6 patients with germline D49H mutation located in the transactivation domain 2 of p53 protein, since the mutation seemed to be prevalent in cancer patients and to be pathogenic. According to the initial survey for family history of the proband with the germline TP53 D49H mutation, one osteosarcoma patient and his pedigree fulfill the criteria for Li-Fraumeni-like syndrome and the 2009 Chompret criteria for germline TP53 mutation screening. Since this patient possesses double germline mutations of TP53 D49H and A159D, further studies are required to evaluate contribution of the D49H mutation in this morbidity. The remaining 5 patients had family histories of cancer, but none fulfills the criteria either for the Li-Fraumeni/Li-Fraumeni-like syndromes or the 2009 Chompret criteria for germline TP53 mutation screening. It is possible to postulate that the germline TP53 D49H mutation is likely to be low-penetrant in some pedigrees. The present study also indicates that the survey for the germline TP53 mutation plays an important role in clinical practice as it will prevent mistaking cancer patients with unusual heredities for sporadic cases.

  4. Cardiovascular and Stroke Risk in Japanese Hemodialysis Patients With Atrial Fibrillation.

    PubMed

    Hasegawa, Jumpei; Bieber, Brian; Larkina, Maria; Robinson, Bruce M; Wakai, Sachiko; Akizawa, Tadao; Saito, Akira; Fukuhara, Shunichi; Akiba, Takashi

    2016-12-01

    Atrial fibrillation is one of the most common arrhythmias in hemodialysis patients. We evaluated its clinical outcomes among hemodialysis patients with atrial fibrillation in Japan. Using data derived from the Japanese Dialysis Outcomes and Practice Patterns Study, we analyzed backgrounds and outcomes among hemodialysis patients with and without atrial fibrillation in Japan. Among 7002 hemodialysis patients, the prevalence of atrial fibrillation was 5.7% and the incidence was 0.2 per 100 patient-years. Atrial fibrillation was independently associated with all-cause mortality (hazard ratio, 1.32; 95% confidence interval, 1.02-1.71) and cardiovascular events (hazard ratio, 1.39; 95% confidence interval, 1.15-1.68), but not with stroke events (hazard ratio, 0.77; 95% confidence interval, 0.55-1.06) after adjustment for other variables. We conclude that patients with atrial fibrillation experienced higher mortality and more cardiovascular events than did patients without atrial fibrillation, although the risk of stroke was lower than expected.

  5. Clinical and Immunological Studies of 332 Japanese Patients Tentatively Diagnosed as Anti-BP180-type Mucous Membrane Pemphigoid: A Novel BP180 C-terminal Domain Enzyme-linked Immunosorbent Assay.

    PubMed

    Yasukochi, Atsushi; Teye, Kwesi; Ishii, Norito; Hashimoto, Takashi

    2016-08-23

    Diagnosis of anti-BP180-type mucous membrane pemphigoid (BP180-MMP) is frustrated by the difficulty of detecting BP180 reactivity. A total of 721 patients with suspected MMP, selected from a cohort of 4,698 patients with autoimmune bullous disease (AIBD), were included in this study. Of these, 332 patients were tentatively diagnosed as BP180-MMP if they showed IgG/IgA reactivity with the epidermal side of 1M NaCl-split-skin and/or positive reactivity with BP180 in at least one of our antigen detection methods. Clinically, a predominance of female patients was found. Oral mucosal and cutaneous lesions were found in 85.5% and 41.0% of patients, respectively, and frequent treatments were systemic steroids, tetracycline/minocycline and diaminodiphenyl sulfone. Various immunological methods, including a newly developed BP180 C-terminal domain enzyme-linked immunosorbent assay (ELISA), revealed frequent reactivity with BP180 C-terminal and NC16a domains. Some patients reacted with BP180 and other antigens, indicating that BP180-MMP tends to concur with other AIBDs. This large study of patients with suspected BP180-MMP indicates the difficulty of diagnosis of BP180-MMP and the diagnostic usefulness of BP180 C-terminal domain ELISA.

  6. Clinical Characteristics of Severe Japanese Encephalitis: A Case Series from South Korea.

    PubMed

    Sunwoo, Jun-Sang; Lee, Soon-Tae; Jung, Keun-Hwa; Park, Kyung-Il; Moon, Jangsup; Jung, Ki-Young; Kim, Manho; Lee, Sang Kun; Chu, Kon

    2017-08-01

    Japanese encephalitis (JE) virus is a major cause of devastating viral encephalitis, especially in Asia. Although a successful vaccination program led to its near-elimination over three decades in South Korea, the incidence of JE has increased since 2010. The present study investigated the clinical manifestations, laboratory findings, and factors affecting neurological outcomes of reemerging JE. We retrospectively reviewed medical records of laboratory-confirmed JE patients who presented with acute encephalitis syndrome at three tertiary hospitals between 2010 and 2015. A total of 17 patients with JE were identified. Their median age was 51 years, and 10 (58.5%) were men. The most common symptoms and signs were fever (94.1%), altered consciousness (94.1%), and headache (80.2%). Hyporeflexia (47.1%), seizures (35.2%), abnormal brainstem reflex (23.5%), and flaccid weakness (17.6%) were also noted. Brain imaging revealed thalamic lesions in all patients, with the hippocampus, midbrain, basal ganglia, and cerebral cortex affected to varying degrees. Sixteen patients (94.1%) required management in the intensive care unit with mechanical ventilation due to neurological deterioration. At the time of discharge, 11 (64.7%) had poor recovery, defined as Glasgow coma scale scores of less than 8, and remained ventilator dependent. Comparison between the two outcome groups indicated that midbrain involvement (P = 0.028) and rapid deterioration (P = 0.005) were associated with severe neurological sequelae. Given that JE is a vaccine-preventable disease, vaccination for adults should be considered in response to the reemergence of JE.

  7. Antibodies to neural and non-neural autoantigens in Japanese patients with CNS demyelinating disorders.

    PubMed

    Watanabe, Mitsuru; Kondo, Takayuki; Murakata, Kenji; Kageyama, Takashi; Shibata, Yoko; Takahashi, Toshiyuki; Nomura, Kyoichi; Matsumoto, Sadayuki

    2014-09-15

    Anti-aquaporin 4 (AQP4) antibodies (Abs) are essential in neuromyelitis optica spectrum disorders (NMOSD), but the relationship between CNS demyelinating disorders (CNSDD) and other neural Abs remains unclear. Here we screened anti-neural Abs in the sera of 70 Japanese CNSDD patients. While two had only demyelinating events among three anti-N-methyl-d-aspartate receptor (NMDAR) Ab-positive subjects, the other subject who also had anti-AQP4 Abs experienced episodes of anti-NMDAR encephalitis and of NMOSD. Major lesions in the three anti-contactin-associated protein 2 Ab-positive subjects were infratentorial, including one co-carrying anti-AQP4 Abs. Thus, autoantibodies can be clinically silent, but multiple autoantibodies may participate in the pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Japanese and non-Japanese patient outcomes in the PLATINUM randomized trial comparing the PROMUS Element and XIENCE V everolimus-eluting stents.

    PubMed

    Saito, Shigeru; Hagiwara, Nobuhisa; Seki, Atsushi; Igarashi, Keiichi; Muramatsu, Toshiya; Yajima, Junji; Yokoi, Hiroyoshi; Nakamura, Masato; Fujii, Kenshi; Isshiki, Takaaki; Stone, Gregg W; Teirstein, Paul S; Meredith, Ian T; Allocco, Dominic J; Dawkins, Keith D

    2014-08-01

    The PLATINUM randomized trial enrolled 1530 patients treated with either the platinum chromium PROMUS Element everolimus-eluting stent (PtCr-EES; Boston Scientific, Natick, MA, USA) or the predicate cobalt chromium PROMUS/XIENCE V EES (CoCr-EES; manufactured as XIENCE V by Abbott Vascular, Santa Clara, CA, USA also distributed as PROMUS by Boston Scientific), including 124 patients from Japanese sites. This substudy examines 2-year outcomes in the Japanese and non-Japanese cohorts. Patients with 1 or 2 de novo native coronary artery lesions (baseline vessel diameter ≥2.50mm to ≤4.25mm and length ≤24mm) were randomized 1:1 to PtCr-EES (N=63 patients in Japan) versus CoCr-EES (N=61 patients in Japan). Several significant differences were noted in baseline demographics, lesion characteristics, and procedural technique between Japanese and non-Japanese patients, including longer fluoroscopy time, less use of contrast, and greater post-dilatation usage and maximum pressure in Japan. Dual antiplatelet usage at 2 years was also higher in Japan. Despite these differences, the 2-year rates of target lesion failure were comparable in patients treated with PtCr-EES and CoCr-EES both in Japan (3.2% vs 5.0% respectively, p=0.68) and outside Japan (4.7% vs 5.9% respectively, p=0.33; p for interaction=0.82). This PLATINUM study subanalysis suggests that the PtCr-EES and CoCr-EES provide comparable safety and efficacy in both Japanese and non-Japanese patients. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  9. High prevalence of primary biliary cirrhosis and disease-associated autoantibodies in Japanese patients with systemic sclerosis.

    PubMed

    Imura-Kumada, Sayako; Hasegawa, Minoru; Matsushita, Takashi; Hamaguchi, Yasuhito; Encabo, Susan; Shums, Zakera; Norman, Gary L; Takehara, Kazuhiko; Fujimoto, Manabu

    2012-11-01

    To investigate the prevalence of primary biliary cirrhosis (PBC) and PBC-associated autoantibodies in Japanese systemic sclerosis (SSc) patients. Clinical data from 225 Japanese SSc patients were retrospectively obtained. Serum samples from these patients were examined for PBC-associated autoantibodies, anti-mitochondrial M2 antibodies (AMA), anti-sp100 antibodies (anti-sp100), and anti-gp210 antibodies (anti-gp210) by enzyme-linked immunosorbent assay. Of 225 patients, 37 (16.4%) had AMA, 13 (5.8%) had anti-sp100, and 3 (1.3%) had anti-gp210. Three patients were positive for both AMA and anti-sp100, and 2 were positive for both AMA and anti-gp210. PBC was found in 22 (9.8%) patients positive for AMA with or without anti-sp100 or anti-gp210, but not in those with anti-sp100 or anti-gp210 without AMA. Furthermore, 13 patients lacking these three antibodies were diagnosed with or suspected of PBC by liver biopsy and/or their clinical manifestation. Multivariable analysis revealed that AMA and anti-centromere antibodies were independently associated with PBC in SSc patients, while anti-sp100 and anti-gp210 were not. This study has demonstrated even higher prevalence of both PBC-associated autoantibodies and PBC in the Japanese SSc population than in the Caucasian SSc population. AMA and anti-centromere antibodies are likely to indicate increasing risk of PBC in SSc patients.

  10. Risk factors associated with relapse or infectious complications in Japanese patients with microscopic polyangiitis.

    PubMed

    Kitagawa, Kiyoki; Furuichi, Kengo; Sagara, Akihiro; Shinozaki, Yasuyuki; Kitajima, Shinji; Toyama, Tadashi; Hara, Akinori; Iwata, Yasunori; Sakai, Norihiko; Shimizu, Miho; Kaneko, Shuichi; Wada, Takashi

    2016-10-01

    The prevention of relapse and infection complications during remission maintenance therapy is required to improve the prognosis of patients with microscopic polyangiitis (MPA) showing rapidly progressive glomerulonephritis (RPGN). The clinicopathological characteristics of patients with ANCA-positive MPA were examined to determine the risk factors for relapse or infectious complications after remission induction therapy. The study population consisted of 52 patients diagnosed as ANCA-positive MPA showing RPGN from 2002 to 2012, after publication of the Japanese guideline for RPGN. The clinicopathological findings were examined between the presence and absence of relapse or infectious complications. The value of vasculitis damage index (VDI) was high for the relapse group and VDI value was identified as the leading factor associated with relapse [hazard ratio (HR) 3.36, 95 % confidence interval (CI) 1.58-7.12, P < 0.01]. On the other hand, the values of Birmingham Vasculitis Activity Score, clinical grade category of RPGN at diagnosis, and VDI at remission were high in the infectious group. Furthermore, clinical grade category of RPGN was the leading factor associated with infectious complications (HR 5.30, 95 % CI 1.41-19.9, P = 0.01). The disease activity at diagnosis and severity of organ damage at remission were associated with relapse and infectious complications during remission maintenance therapy and infectious complication affected kidney survival and all-cause mortality in patients with ANCA-positive MPA exhibiting RPGN.

  11. Clinical characteristics of Japanese candidates for lung transplant for interstitial lung disease and risk factors for early death while on the waiting list.

    PubMed

    Higo, Hisao; Kurosaki, Takeshi; Ichihara, Eiki; Kubo, Toshio; Miyoshi, Kentaroh; Otani, Shinji; Sugimoto, Seiichiro; Yamane, Masaomi; Miyahara, Nobuaki; Kiura, Katsuyuki; Miyoshi, Shinichiro; Oto, Takahiro

    2017-07-01

    Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  12. Retrospective Study of Japanese Patients with Schizophrenia Treated with Aripiprazole

    PubMed Central

    Tanioka, Tetsuya; Fuji, Syoko; Kataoka, Mika; King, Beth; Tomotake, Masahito; Yasuhara, Yuko; Locsin, Rozzano; Sekido, Keiko; Mifune, Kazushi

    2012-01-01

    Aim. The purpose of this retrospective study was to evaluate changes in clinical indicators which influence the quality of life (QOL) of patients with schizophrenia treated by antipsychotic therapy before and after switching to aripiprazole. Methods. A retrospective chart review of 27 patients diagnosed with schizophrenia and who were switched from one antipsychotic to aripiprazole was performed. Clinical indicators about the daily dosage of antipsychotics and antiparkinsonian drugs, psychiatric condition, and glucose/lipid metabolism, clinical evaluation by nursing observation were used to measure the responsiveness of subjects to aripiprazole. Results. Of the 27 subjects, 14 responded to the switch to aripiprazole with significant improvement of the Brief Psychiatric Rating Scale (BPRS) score (P = 0.04), significant decrease in dosage of antipsychotics in 71% of patients (P = 0.03), and tendency toward reduction in dosage of antiparkinsonian drugs (P = 0.07) and body mass index (BMI) (P = 0.06). However, 8 of 27 subjects had a significant increase in lipid levels after switching to aripiprazole (P = 0.01). Conclusion. QOL for subjects who responded to the switch to aripiprazole improved as indicated by lower doses of antipsychotic and antiparkinson medications, improvement in BPRS score, and a decrease in BMI. Results indicate little influence on patient's QOL. PMID:22970386

  13. Validity of the Japanese version of functional assessment of cancer therapy-gastric (FACT-Ga) and its sensitivity to ascites volume change: a retrospective analysis of Japanese clinical trial participants.

    PubMed

    Maeda, Hiromichi; Sato, Maho; Kobayashi, Michiya; Takiguchi, Nobuhiro; Yoshikawa, Takaki; Yoshino, Shigefumi; Yoshida, Kazuhiro; Tsuburaya, Akira; Sakamoto, Junichi; Morita, Satoshi

    2016-11-01

    The functional assessment of cancer therapy-gastric (FACT-Ga) questionnaire was designed to evaluate quality of life (QOL) in patients with gastric cancer. We aimed to explore the reliability and validity of FACT-Ga in Japanese patients, and assess the sensitivity of the gastric cancer subscale for detecting changes in cancer-related variables over time. The Japanese version of FACT-Ga was used, and data were obtained from Japanese patients who participated in either of two clinical trials: treatment for advanced or recurrent gastric cancer with ascites (advanced-GC group), or adjuvant chemotherapy after curative resection of gastric cancer (adjuvant group). Psychometric data including data used to determine reliability, internal consistency, and clinical validity were analyzed. Clinical validity was evaluated by comparing subscale scores for patients in the two groups, and by comparing subscale scores for patients with different performance status scores. Correlation between gastric cancer subscale scores and gastric cancer-related variables was also examined. In addition, sensitivity of the gastric cancer subscale to changes in ascites volume, abdominal girth, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) was examined by evaluating their correlation in the advanced-GC group. We collected data on 156 patients (62 advanced-GC group patients and 94 adjuvant group patients). Response rates for the subscales were over 80 % at most time points for both the groups. Cronbach's coefficient alpha revealed good internal consistency for each subscale. At baseline, the adjuvant group had higher QOL scores than the advanced-GC group (P < 0.05), and QOL scores for patients with different performance status scores differed significantly. Changes in gastric cancer subscale scores showed statistically significant correlation with changes in ascites volume (Spearman's rank correlation coefficient, 0.5; P < 0.05). FACT-Ga is reliable and clinically valid

  14. Difference in patient profiles and outcomes in Japanese versus American patients undergoing coronary revascularization (collaborative study by CREDO-Kyoto and the Texas Heart Institute Research Database).

    PubMed

    Kohsaka, Shun; Kimura, Takeshi; Goto, Masashi; Lee, Vei-Vei; Elayda, Macarthur; Furukawa, Yutaka; Fukushima, Masanori; Komeda, Masashi; Sakata, Ryuuzou; Willerson, James T; Wilson, James M; Kita, Toru

    2010-06-15

    Although coronary revascularization is common in both Japan and the United States (US), no direct comparison has been performed to demonstrate differences in the clinical characteristics and long-term outcomes of patients in these 2 countries. We analyzed the preprocedural, in-hospital, and long-term data from the Coronary Revascularization Demonstrating Outcome registry (Kyoto, Japan) and the Texas Heart Institute Research Database (Houston, Texas) of 16,100 patients who had undergone elective, initial percutaneous coronary intervention or coronary artery bypass grafting. The Japanese procedures were performed from 2000 to 2002 (n = 8,871, follow-up period 3.5 years, interquartile range 2.6 to 4.3) and the US procedures from 1999 to 2003 (n = 7,229, follow-up period 5.2 years, interquartile range 3.8 to 6.5). The Japanese patients tended to be older (mean age 67.2 vs 62.7 years; p <0.001), to smoke (52.9% vs 46.0%; p <0.001), and to have diabetes (39.2% vs 31.0%; p <0.001) and stroke (16.4% vs 5.0%; p <0.001). The US patients were more obese (body mass index 23.7 vs 29.3 kg/m(2); p <0.001), with greater rates of systemic atherosclerotic disease. Both groups had a similar in-hospital mortality rate (Japanese patients 0.9% vs US patients 1.1%; p = 0.19) and crude long-term mortality rate (Japanese patients 27.7/1,000 person-years, US patients 28.2/1,000 person-years; p = 0.35). After adjustment for known predictors, the US group had greater long-term mortality than the Japanese group (hazard ratio 1.71, 95% confidence interval 1.50 to 1.95; p <0.001). This finding was consistent among all high-risk subgroups. In conclusion, the 2 registries showed similar crude outcomes but important differences in patient risk factors such as obesity. In the adjusted analysis, the Japanese patients had better outcomes than did the US patients. Additional study is needed to assess the effect of ethnic and risk factor variations on coronary artery disease.

  15. Correlations of Japanese Orthopaedic Association Scoring Systems with Gait Parameters in Patients with Degenerative Spinal Diseases.

    PubMed

    Zheng, Chen-Fan; Liu, Yan-Cheng; Hu, Yong-Cheng; Xia, Qun; Miao, Jun; Zhang, Ji-Dong; Zhang, Kuan

    2016-11-01

    Japanese Orthopaedic Association (JOA) scoring systems were developed to evaluate the neurological function of patients with cervical or lumbar degeneration. As patient-based and multi-dimensional clinical evaluation tools, these systems should be capable of reflecting the walking disability of patients. The association between JOA scores and gait parameters, however, are not well characterized. The purpose of this study was to determine the correlations between JOA scores and gait parameters of patients with cervical spondylotic myelopathy (CSM) and lumbar intervertebral disc herniation (LDH). A total of 32 CSM and 30 LDH patients with gait dysfunction were recruited for the present study. All patients were diagnosed by two senior orthopaedic doctors and evaluated with JOA scoring systems. A body-mounted motion analyzer, the Intelligent Device for Energy Expenditure and Activity (IDEEA), was applied to measure gait parameters of patients across 30 m of flat floor in an orthopaedic ward. A linear regression model was used to determine the correlations between JOA scores and gait parameters. Multiple linear regressions were used to identify the relationships between subsections of the JOA systems and gait parameters. Japanese Orthopaedic Association scores of LDH patients from the JOA lumbar scoring system are significantly correlated with gait speed (R (2) = 0.557, P < 0.001) and stride length (R (2) = 0.544, P < 0.001). JOA scores are also correlated with double support duration, step duration, cycle duration and cadence, and weakly correlated with single support duration. For the four subsections of the JOA lumbar scoring system, "restriction of activities of daily living" is the significant predictor of all gait parameters, especially gait speed (R (2) = 0.573, P < 0.001) and stride length (R (2) = 0.553, P < 0.001). However, JOA scores of CSM patients from the JOA cervical scoring system are only weakly correlated with these measures (all R (2) < 0.3). For

  16. Plasma free metanephrines in the diagnosis of pheochromocytoma: diagnostic accuracy and strategies for Japanese patients.

    PubMed

    Tanaka, Yuko; Isobe, Kazumasa; Ma, Enbo; Imai, Tsuneo; Kikumori, Toyone; Matsuda, Tadashi; Maeda, Yuji; Sakurai, Akihiro; Midorikawa, Sanae; Hataya, Yuji; Kato, Taiya; Kamide, Kei; Ikeda, Yukihiro; Okada, Yosuke; Adachi, Masahiro; Yanase, Toshihiko; Takahashi, Hideto; Yokoyama, Chie; Arai, Yusuke; Hashimoto, Koichi; Shimano, Hitoshi; Hara, Hisato; Kawakami, Yasushi; Takekoshi, Kazuhiro

    2014-01-01

    Measuring the levels of the plasma free metanephrines (PFMs) represents a recently developed and promising test for the diagnosis of pheochromocytoma in the United States and Europe. As this test has not yet been evaluated in Japan, it is necessary to evaluate the diagnostic efficacy of measuring the levels of PFMs compared with the standard measurement of the urinary excretion of metanephrines (uMNs) whose reliability is well established to detect of pheochromocytoma. A total of 101 Japanese subjects clinically suspected of having pheochromocytoma in were included in this study. Subsequently, we prospectively measured the PFMs levels in all patients, compared with those of biochemical markers of the catecholamine secretion and metabolisms in the plasma and urine. All subjects with adrenal tumors underwent tumor excision. Data were available for 84 of the 101 patients, 47 of whom had histopathologically proven pheochromocytoma and 37 were finally diagnosed with non-pheochromocytoma. The results of comparisons in the accuracy of measurement for diagnosis of pheochromocytoma between PFMs and the urinary excretion of metanephrines (uMNs) were 0.980 VS 0.951 for AUC of receiver operatorating characteristic (ROC) curve, 0.957 VS 0.894 for sensitivity, and 0.973 VS 0.946 for specificity, respectively. Although the differences were small, the results of our study definitely demonstrated that measurement of PFMs was not inferior to standard urinary metanephrines (uMNs) measurement, which is established to be the most reliable biochemical method to detect pheochromocytoma. This study clearly shows measuring the PFMs levels to be a reliable and efficient method for diagnosing pheochromocytoma in Japanese patients, as demonstrated in previous reports.

  17. Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma

    PubMed Central

    Kawakami, Hisato; Okamoto, Isamu; Terao, Kyoichi; Sakai, Kazuko; Suzuki, Minoru; Ueda, Shinya; Tanaka, Kaoru; Kuwata, Kiyoko; Morita, Yume; Ono, Koji; Nishio, Kazuto; Nishimura, Yasumasa; Doi, Katsumi; Nakagawa, Kazuhiko

    2013-01-01

    Human papillomavirus (HPV) is a major etiologic factor for oropharyngeal squamous cell carcinoma (OPSCC). However, little is known about HPV-related OPSCC in Japan. During the study, formalin-fixed, paraffin-embedded OPSCC specimens from Japanese patients were analyzed for HPV DNA by the polymerase chain reaction (PCR) and for the surrogate marker p16 by immuno-histochemistry. For HPV DNA-positive, p16-negative specimens, the methylation status of the p16 gene promoter was examined by methylation-specific PCR. Overall survival was calculated in relation to HPV DNA and p16 status and was subjected to multivariate analysis. OPSCC cell lines were examined for sensitivity to radiation or cisplatin in vitro. The study results showed that tumor specimens from 40 (38%) of the 104 study patients contained HPV DNA, with such positivity being associated with tumors of the tonsils, lymph node metastasis, and nonsmoking. Overall survival was better for OPSCC patients with HPV DNA than for those without it (hazard ratio, 0.214; 95% confidence interval, 0.074–0.614; P = 0.002). Multivariate analysis revealed HPV DNA to be an independent prognostic factor for overall survival (P = 0.015). Expression of p16 was associated with HPV DNA positivity. However, 20% of HPV DNA-positive tumors were negative for p16, with most of these tumors manifesting DNA methylation at the p16 gene promoter. Radiation or cisplatin sensitivity did not differ between OPSCC cell lines positive or negative for HPV DNA. Thus, positivity for HPV DNA identifies a distinct clinical subset of OPSCC with a more favorable outcome in Japanese. PMID:24403267

  18. Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma.

    PubMed

    Kawakami, Hisato; Okamoto, Isamu; Terao, Kyoichi; Sakai, Kazuko; Suzuki, Minoru; Ueda, Shinya; Tanaka, Kaoru; Kuwata, Kiyoko; Morita, Yume; Ono, Koji; Nishio, Kazuto; Nishimura, Yasumasa; Doi, Katsumi; Nakagawa, Kazuhiko

    2013-12-01

    Human papillomavirus (HPV) is a major etiologic factor for oropharyngeal squamous cell carcinoma (OPSCC). However, little is known about HPV-related OPSCC in Japan. During the study, formalin-fixed, paraffin-embedded OPSCC specimens from Japanese patients were analyzed for HPV DNA by the polymerase chain reaction (PCR) and for the surrogate marker p16 by immuno-histochemistry. For HPV DNA-positive, p16-negative specimens, the methylation status of the p16 gene promoter was examined by methylation-specific PCR. Overall survival was calculated in relation to HPV DNA and p16 status and was subjected to multivariate analysis. OPSCC cell lines were examined for sensitivity to radiation or cisplatin in vitro. The study results showed that tumor specimens from 40 (38%) of the 104 study patients contained HPV DNA, with such positivity being associated with tumors of the tonsils, lymph node metastasis, and nonsmoking. Overall survival was better for OPSCC patients with HPV DNA than for those without it (hazard ratio, 0.214; 95% confidence interval, 0.074-0.614; P = 0.002). Multivariate analysis revealed HPV DNA to be an independent prognostic factor for overall survival (P = 0.015). Expression of p16 was associated with HPV DNA positivity. However, 20% of HPV DNA-positive tumors were negative for p16, with most of these tumors manifesting DNA methylation at the p16 gene promoter. Radiation or cisplatin sensitivity did not differ between OPSCC cell lines positive or negative for HPV DNA. Thus, positivity for HPV DNA identifies a distinct clinical subset of OPSCC with a more favorable outcome in Japanese.

  19. Quality of life of Japanese patients with chronic hepatitis C treated with ledipasvir and sofosbuvir

    PubMed Central

    Younossi, Zobair M.; Stepanova, Maria; Omata, Masao; Mizokami, Masashi; Walters, Mercedes; Hunt, Sharon

    2016-01-01

    Abstract The interferon (IFN)-free regimens for chronic hepatitis C (CHC) have high efficacy and superior health-related quality of life (HRQOL) in European/North American patients. The impact of these regimens on HRQOL of the Japanese CHC patients is not known. The Short Form-36 was administered before, during, and after treatment to CHC patients with genotype 1 treated with ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) for 12 weeks and genotype 2 treated with SOF + RBV for 12 weeks in clinical trials. The HRQOL data were analyzed with reference to treatment regimens and clinical factors. A total of 494 CHC patients were included (19% cirrhotic, 69% genotype 1, 52% treatment-naive; 153 received SOF + RBV, 170 received LDV/SOF + RBV, 171 received LDV/SOF). The sustained virologic response-12 rates for these regimens were 97%, 98%, and 100%, respectively. CHC patients treated with LDV/SOF, SOF + RBV, or LDV/SOF + RBV regimens had similar HRQOL scores at baseline. During treatment, more adverse events were experienced by those treated with RBV-containing regimens (46% vs 22%, P < 0.0001). The decrements in HRQOL were also significant in RBV groups: up to −3.8 points (treatment week-4), −5.2 (treatment week-12), and −3.2 (posttreatment week-12) (all P < 0.001). In contrast, RBV-free regimen (LDV/SOF) was associated with an improvement in HRQOL up to +4.1 points throughout the treatment (P < 0.01). In multivariate analysis, the use of RBV was independently associated with lower HRQOL during and after treatment (beta up to −6.4 points, P = 0.0001). Japanese CHC patients treated with RBV-containing regimens show mild HRQOL impairment. In contrast, patients treated with LDV/SOF not only showed high efficacy but also improvement of HRQOL. PMID:27537553

  20. Antimicrobial activities of ozenoxacin against isolates of propionibacteria and staphylococci from Japanese patients with acne vulgaris.

    PubMed

    Nakajima, Akiko; Ikeda, Fumiaki; Kanayama, Shoji; Okamoto, Kazuaki; Matsumoto, Tatsumi; Ishii, Ritsuko; Fujikawa, Akira; Takei, Katsuaki; Kawashima, Makoto

    2016-08-01

    Ozenoxacin, a novel non-fluorinated topical quinolone, was assessed for in vitro antimicrobial activity against clinical isolates of propionibacteria and staphylococci according to the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. The isolates used in this study were collected from Japanese patients with acne vulgaris during a period from 2012 to 2013. The MIC90s of ozenoxacin against Propionibacterium acnes (n=266), Propionibacterium granulosum (n=10), Staphylococcus aureus (n=23), Staphylococcus epidermidis (n=229) and other coagulase-negative staphylococci (n=82) were ≤0.06, ≤0.06, ≤0.06, 0.125 and ≤0.06 µg ml-1, respectively. The antimicrobial activity of ozenoxacin against the clinical isolates of propionibacteria and staphylococci was greater than that of five reference antimicrobial agents which have been used for the treatment of acne vulgaris. The MICs of ozenoxacin were correlated with those of nadifloxacin in P. acnes and S. epidermidis isolates. However, the MICs of ozenoxacin were 0.25-0.5 µg ml-1 and 0.5-8 µg ml-1 against nadifloxacin-resistant P. acnes (MIC: ≥8 µg ml-1; n=8) and S. epidermidis (MIC: ≥64 µg ml-1; n=10), respectively. These results indicated the potent antimicrobial activity against P. acnes and S. epidermidis isolates resistant to nadifloxacin. Topical ozenoxacin could represent an alternative therapeutic drug for acne vulgaris based on its potent antimicrobial activity against the isolates of propionibacteria and staphylococci from acne patients.

  1. Factors associated with Japanese dentists encouraging patients to use dental floss.

    PubMed

    Nakamura, F; Hirayama, Y; Morita, I; Nakagaki, H

    2011-03-01

    The objective of this study was to clarify to what extent Japanese dentists recommend dental floss and what factors influence dentists in encouraging their patients to use dental floss. The subjects in this study were 291 dentists who were directors of dental clinics, selected by stratified sampling by age. Dentists whose teachers at dental school had demonstrated dental flossing tended to recommend patients to use dental floss 2.2 (1.0-4.6: 95% CI) times more frequently compared with those who did not see demonstrations of flossing at dental school. Respondents who considered that using dental floss was very easy and easy, moderate, and difficult recommended patients to use dental floss 45.4 (11.2-183.9), 17.4 (6.6-45.8) and 5.9 (2.5-14.1) times more frequently, respectively, compared with those who considered it very difficult. Respondents who considered that using dental floss was effective, fairly effective or very effective in preventing dental caries recommended patients to use dental floss 3.8 (1.7-8.6), 3.8 (1.7-8.8) and 9.1 (3.6-23.0) times more frequently respectively, compared with those who considered it ineffective or only slightly effective. The demonstration of the use of dental floss by teachers at their dental schools gave dentists a good impression and a positive opinion of dental flossing. This was closely associated with recommendations by dentists to their patients to use dental floss.

  2. Icodextrin reduces mortality and the drop-out rate in Japanese peritoneal dialysis patients.

    PubMed

    Kuriyama, Renjiro; Tranaeus, Anders; Ikegami, Tadashi

    2006-01-01

    Although numerous reports have shown that the use of icodextrin solution, as compared with conventional dextrose solutions, provides various clinical benefits, data on the impact of icodextrin solution on mortality and drop-out are sparse. In the present retrospective study, we compared clinical outcomes in a large cohort of patients prescribed either icodextrin or dextrose solution for the long dwell. A total of 7808 patients across Japan who were using Baxter peritoneal dialysis (PD) solutions in 2004 were included in this cross-sectional analysis. Outcomes data were retrieved from the Baxter Japan database. The annual drop-out rate in the icodextrin group (8.9%) was significantly (p < 0.0001) lower than that in the dextrose group (14.5%). The annual mortality rate was also lower (6.6% vs. 13.5%, p < 0.0001). Using data from the 2000 report of the Japanese Society for Dialysis Therapy, the relative risk of death in the icodextrin group, regardless of PD duration, was consistently lower than that in hemodialysis patients. These results indicate that, in PD, the use of icodextrin solution (as compared with dextrose solution) significantly reduces both mortality and drop-out rate.

  3. Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

    PubMed

    Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

    2013-01-01

    The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

  4. Mutations in the genes encoding eukaryotic translation initiation factor 2B in Japanese patients with vanishing white matter disease.

    PubMed

    Shimada, Shino; Shimojima, Keiko; Sangu, Noriko; Hoshino, Ai; Hachiya, Yasuo; Ohto, Tatsuyuki; Hashi, Yuichiro; Nishida, Katsuya; Mitani, Maki; Kinjo, Saori; Tsurusaki, Yoshinori; Matsumoto, Naomichi; Morimoto, Masafumi; Yamamoto, Toshiyuki

    2015-11-01

    Vanishing white matter disease (VWM) is a chronic, progressive leukoencephalopathy associated with episodes of rapid deterioration following minor stress events such as head traumas or infectious disorders. The white matter of the patients with VWM exhibits characteristic radiological findings. The genes encoding all five subunits of eukaryotic translation initiation factor 2B (EIF2B) were analyzed in patients, who were tentatively diagnosed with VWM, by Sanger sequencing. Seven mutations were identified in the genes encoding the subunits 1, 2, 4, and 5 of EIF2B. Among them, one mutation (p.V83E) in the subunit 2 (EIF2B2) was recurrently identified in three alleles, indicating the most common mutation in Japanese patients with VWM. Two patients were homozygous, and the other four patients were compound heterozygous. All patients showed white matter abnormalities with various degrees. One patient showed manifestations of end-stage VWM disease. Some patients showed late onset and slow progression associated with brain magnetic resonance imaging displaying T2 high intensity only in the deep white matter. There was clinical heterogeneity among patients with VWM. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  5. Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma.

    PubMed

    Tsuchiya, Norihiko; Narita, Shintaro; Inoue, Takamitsu; Hasunuma, Naoko; Numakura, Kazuyuki; Horikawa, Yohei; Satoh, Shigeru; Notoya, Takeshi; Fujishima, Naohito; Hatakeyama, Shingo; Ohyama, Chikara; Habuchi, Tomonori

    2013-03-01

    The aim of this study was to evaluate the clinical factors, drug-related genetic polymorphisms, and human leukocyte antigen (HLA) types to determine the association with sorafenib-induced high-grade skin rash (HGSR) in Japanese patients with advanced renal cell carcinoma (RCC). A total of 55 patients with advanced RCC treated with sorafenib were analyzed retrospectively. Of these, 33 patients were subjected to HLA typing and polymorphism analyses of CYP3A5, ABCB1, ABCC2, and UGT1A1, which are involved in the metabolism and membrane transport of sorafenib. Grade 3 or higher SR developed in 12 (22%), and a higher incidence was observed in female patients than in male patients (40 vs. 15%, P=0.046). The initial dose, initial dose per body weight, and initial dose per body surface area in patients with HGSR were significantly higher than those in patients without HGSR. Patients with the ABCC2 -24CC genotype were at a significantly higher risk of SR than those with the CT genotype (35 vs. 0%, P=0.032). HLA-A*24 was significantly associated with the occurrence of HGSR (P=0.049). Our finding suggested that women, higher initial dose per body weight or body surface area, the ABCC2 -24CC genotype, and HLA-A*24 are associated with the risk of sorafenib-induced HGSR in Japanese RCC patients.

  6. Obstructive sleep apnea syndrome causes a pseudo-Cushing's state in Japanese obese patients with type 2 diabetes mellitus.

    PubMed

    Tamada, Daisuke; Otsuki, Michio; Kashine, Susumu; Hirata, Ayumu; Onodera, Toshiharu; Kitamura, Tetsuhiro; Shimomura, Iichiro

    2013-01-01

    Activation of the hypothalamic-pituitary-adrenal axis has been reported in some patients with the obstructive sleep apnea syndrome (OSAS). In current study, we investigated whether OSAS affect the screening test for subclinical Cushing's disease using 0.5 mg overnight dexamethasone suppression test (DST) in Japanese obese diabetic patients with OSAS. Among Japanese obese patients with type 2 diabetes mellitus who had been hospitalized in our department, we selected 20 patients with moderate to severe untreated OSAS (apnea-hypoxia index, AHI, of ≥15 events/hour). All patients underwent 0.5 mg DST. The same test was repeated in patients with positive response of it within a few days after continuous positive airway pressure (CPAP) therapy. We found that five patients showed positive response of DST (25%). Three of these patients continued to use CPAP, and they showed normal response of DST after CPAP therapy. Serum cortisol after 0.5 mg DST measured before CPAP therapy correlated significantly with fasting serum cortisol level (r=0.764, p<0.0001), but not with various clinical parameters, including AHI (p=0.784), body mass index (p=0.984), waist circumference (p=0.957), HbA1c (p=0.261), fasting plasma glucose (p=0.420) and HOMA-IR (p=0.500). Our study show that OSAS causes a pseudo-Cushing's syndrome in obese patients with type 2 diabetes mellitus, which phenomena can be reversed by CPAP therapy.

  7. Frequency and Clinical Implication of the R450H Mutation in the Thyrotropin Receptor Gene in the Japanese Population Detected by Smart Amplification Process 2

    PubMed Central

    Yanagawa, Yoshimaro; Aoki, Tomoyuki; Morimura, Tadashi; Araki, Osamu; Kimura, Takao; Ogiwara, Takayuki; Kotajima, Nobuo; Yanagawa, Masumi; Murakami, Masami

    2014-01-01

    In Japanese pediatric patients with thyrotropin (TSH) resistance, the R450H mutation in TSH receptor gene (TSHR) is occasionally observed. We studied the frequency and clinical implication of the R450H mutation in TSHR in the general population of Japanese adults using smart amplification process 2 (SmartAmp2). We designed SmartAmp2 primer sets to detect this mutation using a drop of whole blood. We analyzed thyroid function, antithyroid antibodies, and this mutation in 429 Japanese participants who had not been found to have thyroid disease. Two cases without antithyroid antibodies were heterozygous for the R450H mutation in TSHR. Thus, the prevalence of this mutation was 0.47% in the general population and 0.63% among those without antithyroid antibodies. Their serum TSH concentrations were higher than the average TSH concentration not only in subjects without antithyroid antibodies but also in those with antithyroid antibodies. The R450H mutation in TSHR is relatively common in the Japanese population and potentially affects thyroid function. The present study demonstrates that the SmartAmp2 method is useful to detect the R450H mutation in TSHR, which is one of the common causes of TSH resistance in the Japanese population. PMID:24895636

  8. Providing written information increases patient satisfaction: a web-based questionnaire survey of Japanese cancer survivors.

    PubMed

    Sakai, Hitomi; Katsumata, Noriyuki; Takahashi, Miyako

    2017-07-01

    The Institute of Medicine (IOM) of the United States recommends that all cancer survivors be provided with a survivorship care plan (SCP), which includes a patient treatment summary and a follow-up care plan. However, SCPs have not been widely adopted in Japan. To provide basic data necessary for implementing SCPs in Japan, we aimed to investigate the forms of clinical and survivorship-related information that Japanese cancer survivors receive from their healthcare providers, and to examine whether written information increases their satisfaction. We performed a cross-sectional online survey of cancer survivors who underwent acute cancer treatment and had at least one follow-up with a physician in the past year. Cancer survivors provided the elements and forms (verbally and/or written) of information they received, as well as the degree of satisfaction with the information provided. Responses were obtained from 545 cancer survivors. Information elements such as surgical procedure (98.3%), surgical outcome (98.1%), and names of administered chemotherapy agents (97.8%) were commonly provided, whereas mental care resources and providers (29.7%), effects on marital relationship and sexual health (35.7%), and effects on fertility (43.4%) were less common. A large proportion of cancer survivors received verbal information only. For 18 of 20 elements, except for effects on fertility and duration of hormonal therapy, satisfaction was significantly higher when both forms of information were provided (P < 0.05). Providing written and verbal explanations of clinical and survivorship-related information can better meet the needs of Japanese cancer survivors.

  9. Blood pressure differences between office and home settings among Japanese normotensive subjects and hypertensive patients.

    PubMed

    Mori, Hisao; Ukai, Hiroshi; Yamamoto, Hareaki; Yuasa, Shouhei; Suzuki, Yoshiro; Chin, Keiichi; Katsumata, Takuma; Umemura, Satoshi

    2017-03-01

    This study attempted to clarify the differences in blood pressure (BP) between the office (clinic) and home settings in patients with controlled, sustained, masked or white-coat hypertension. The following formula was used: office mean systolic BP (omSBP)-mean morning home SBP (mmhSBP)/office mean diastolic BP (omDBP)-mean morning home DBP (mmhDBP). The paired t-test was used for statistical analysis. The omSBP-mmhSBP/omDBP-mmhDBP calculation yielded the following results: among normotensive subjects, -1.1±11.2/-1.7±8.5 mm Hg (mean SBP and mean DBP were higher at home than in the office; n=451, P=0.038 in SBP, P=0.000 in DBP); in controlled hypertensive patients, -0.42±10.9/-2.2±8.2 mm Hg (n=1362, P=0.160 in SBP, P=0.000 in DBP); among sustained hypertensive patients, 5.6±14.7/0.048±9.9 mm Hg (n=1370, P=0.000 in SBP, P=0.857 in DBP); in masked hypertensive patients, -15.3±12.9/-9.3±9.5 mm Hg (n=1308, both P=0.000); and among white-coat hypertensive patients, 23.7±13.2/8.2±9.1 mm Hg (n=580, both P=0.000). Our results showed a difference of 5 mm Hg in SBP among sustained hypertensive patients, as recommended by the Japanese Society of Hypertension Guidelines for the Management of Hypertension; however, in other hypertensive patient types, the differences in SBP and DBP between office and home measurements differed by >5 mm Hg. Office and home BP measurements should be interpreted cautiously, keeping in mind the clinical setting.

  10. Pemphigus: use of the Japanese severity index in 56 Moroccan patients

    PubMed Central

    Benchikhi, Hakima; Nani, Samira; Baybay, Hanane; Amal, Said; Mernissi, Fatim-Zahra

    2013-01-01

    Introduction In pemphigus, there still is no consensus on parameters mesuring clinically the disease severity. The aim of this study is to use the Japanese severity index in Moroccan patients with pemphigus. Methods Multicenter prospective study from September 2007 to September 2009 including consecutive patients with confirmed pemphigus. We used the Japenese severity index for pemphigus. For each patient, the score was calculated at diagnosis and at 6 months of follow-up and correlated to type of pemphigus; mean dosage of corticosteroids and clinical statuts at 6 months: dead or not. Results Fifty six patients were included, 20 men and 36 women, mean age 46.62 ± 15.9 years. At diagnosis, the mean initial score was 7.7 + 2.36; at six months, it was 1.61 + 1.83. The score variation at 6 months and inclusion was 6.19 ± 2.18 for deep pemphigus and 5.43 ± 2.85 for superficial pemphigus (p = 0,3 non significant). At six months, 4 patients were dead: their initial score was 11 + 1.41 while the initial score in the 52 patients was 7.4±2.03 (p = 0,001, significant). Data showed no correlation between initial severity scores and cumulative dosage of corticosteroids at 6 months (Pearson coefficient of correlation 0.144; p = 0.580). Conclusion In this study, initial severity scores for pemphigus were high and decreased at 6 months of treatment. Both deep pemphigus and superficial pemphigus were severe as their score variation was similar. Japenese severity score is useful for Moroccan patients with pemphigus. PMID:24772225

  11. Pemphigus: use of the Japanese severity index in 56 Moroccan patients.

    PubMed

    Benchikhi, Hakima; Nani, Samira; Baybay, Hanane; Amal, Said; Mernissi, Fatim-Zahra

    2013-01-01

    In pemphigus, there still is no consensus on parameters mesuring clinically the disease severity. The aim of this study is to use the Japanese severity index in Moroccan patients with pemphigus. Multicenter prospective study from September 2007 to September 2009 including consecutive patients with confirmed pemphigus. We used the Japenese severity index for pemphigus. For each patient, the score was calculated at diagnosis and at 6 months of follow-up and correlated to type of pemphigus; mean dosage of corticosteroids and clinical statuts at 6 months: dead or not. Fifty six patients were included, 20 men and 36 women, mean age 46.62 ± 15.9 years. At diagnosis, the mean initial score was 7.7 + 2.36; at six months, it was 1.61 + 1.83. The score variation at 6 months and inclusion was 6.19 ± 2.18 for deep pemphigus and 5.43 ± 2.85 for superficial pemphigus (p = 0,3 non significant). At six months, 4 patients were dead: their initial score was 11 + 1.41 while the initial score in the 52 patients was 7.4±2.03 (p = 0,001, significant). Data showed no correlation between initial severity scores and cumulative dosage of corticosteroids at 6 months (Pearson coefficient of correlation 0.144; p = 0.580). In this study, initial severity scores for pemphigus were high and decreased at 6 months of treatment. Both deep pemphigus and superficial pemphigus were severe as their score variation was similar. Japenese severity score is useful for Moroccan patients with pemphigus.

  12. Effectiveness of the Mindfulness Art Therapy Short Version for Japanese Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Ando, Michiyo; Kira, Haruko; Hayashida, Shigeru; Ito, Sayoko

    2016-01-01

    The aim of this study was to investigate the feasibility of the Mindfulness Art Therapy Short Version for Japanese patients with advanced cancer. Patients learned mindfulness practices and then made art to express their feelings in the first session. After receiving instruction on practicing mindfulness 2 weeks later, they participated in a second…

  13. Effectiveness of the Mindfulness Art Therapy Short Version for Japanese Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Ando, Michiyo; Kira, Haruko; Hayashida, Shigeru; Ito, Sayoko

    2016-01-01

    The aim of this study was to investigate the feasibility of the Mindfulness Art Therapy Short Version for Japanese patients with advanced cancer. Patients learned mindfulness practices and then made art to express their feelings in the first session. After receiving instruction on practicing mindfulness 2 weeks later, they participated in a second…

  14. Awareness of salt restriction is not reflected in the actual salt intake in Japanese hypertensive patients.

    PubMed

    Takahashi, Nobuyuki; Tanabe, Kazuaki; Adachi, Tomoko; Nakashima, Ryuma; Sugamori, Takashi; Endo, Akihiro; Ito, Takafumi; Yoshitomi, Hiroyuki; Ishibashi, Yutaka

    2015-01-01

    The Japanese guidelines for hypertension management recommend reducing salt intake to <6 g/day for hypertensive patients. However, it is not currently known whether hypertensive patients' awareness of the recommended reduced salt diet correlates with their actual intake. Therefore, the purpose of this study was to investigate the relationship between actual salt intake of Japanese hypertensive patients and their awareness of the recommended guidelines for reduced dietary salt intake. In total, 236 outpatients (146 males and 90 females) with a mean age 69.7 ± 12.5 years were included in this study. Daily dietary salt intake was estimated using sodium and creatinine concentrations detected in spot urine samples. The patients filled out a questionnaire regarding their awareness of recommended salt restriction for hypertension management. The questionnaire distinguished the patients' awareness of recommended salt restriction in four levels (low, moderate, high and very high). The mean estimated salt intake was 9.72 ± 2.43 g/day. Patients' awareness regarding salt intake in all levels provided in the questionnaire did not correlate with actual salt intake (p = 0.731). Our results demonstrated that Japanese hypertensive outpatients consumed higher levels of salt than the target value recommended by Japanese guidelines. There was no correlation between actual salt intake and patients' awareness of the recommended reduction in salt. These results suggest that monitoring salt intake and informing patients of their actual salt intake are necessary for effective hypertension management.

  15. Reliability of predicted renal function in Japanese patients on cisplatin therapy.

    PubMed

    Yajima, A; Ogawa, C; Yatabe, M; Kondo, N; Saito, S; Suzuki, Y; Uesawa, Y

    2013-09-01

    Cisplatin, cis-Dichlorodiammine platinum (II) (CDDP) remains a major antineoplastic drug for the treatment of solid tumors. Its chief dose-limiting side effect is nephrotoxicity. To make a safe and effective dosing regimen of a drug excreted mainly by the renal route, evaluation of patients' renal function is essential. Creatinine clearance (CLcr) or glomerular filtration rate (GFR) is considered to be a standard renal-function test. Several equations have been used in clinical settings, to predict CLcr and GFR using serum creatinine concentration. We carried out a retrospective analysis of the correlation between 24-hour CLcr measured by a urine collection method; and the predicted CLcr and GFR estimated by various equations such as Jelliffe, Yasuda, Orita, Mawer, Mawer, MDRD and modified MDRD, and Cockcroft-Gault. This study used data from Japanese head-and-neck cancer patients, before and after chemotherapy with CDDP. Slopes of regression lines of scatter plots between measured CLcr and predicted renal function in post-CDDP patients were less compared to pre-CDDP patients. On the other hand, Y-intercepts were noted in the scatter plots on renal function from all equations. These results suggest that evaluation of renal function using predictive formulae may have been over-/under-estimated after CDDP administration.

  16. Dosage, effectiveness, and safety of sertraline treatment for posttraumatic stress disorder in a Japanese clinical setting: a retrospective study.

    PubMed

    Kamo, Toshiko; Maeda, Masaharu; Oe, Misari; Kato, Hiroshi; Shigemura, Jun; Kuribayashi, Kazuhiko; Hoshino, Yuko

    2016-12-07

    Many of the posttraumatic stress disorder (PTSD) treatment guidelines recognize the use of selective serotonin reuptake inhibitors as first-line pharmacological treatment. In Japan, there were no published studies investigating the effectiveness and safety of sertraline for PTSD in a clinical setting. We conducted a retrospective medical chart review of the dosage, effectiveness, and safety of sertraline for the PTSD treatment in Japan. Data were collected from medical charts of patients of PTSD, caused by various types of trauma, who were treated with sertraline between July 2006 and October 2012 during their regular clinical practice. To evaluate the effectiveness, the investigators retrospectively assessed the severity and improvement of the symptoms using the Clinical Global Impressions - Severity and the Clinical Global Impressions - Improvement. The study population was 122 Japanese patients aged ≥18 years with a diagnosis of PTSD who were treated with sertraline (median duration, 10.6 months). Doses ranged from 12.5 to 150 mg/day, mostly 25 and 50 mg/day. The median duration of observation was 10.8 months. Out of those, 50% of patients were regarded as responders by using the Clinical Global Impressions - Improvement at the end of sertraline treatment or the last observation. Two-thirds (65.6%) of patients improved in the severity of PTSD, as assessed by Clinical Global Impressions - Severity, whereas 32.8% showed no change, and 1.6% worsened. Subgroups analyses and logistic regression analyses suggested that the type of traumatic events was the factor with the highest influence on the response rate. The adverse events in this chart review were consistent with the known safety profile of sertraline. There were no reports of serious or severe adverse events considered to be related to sertraline. Our study suggested the effectiveness of sertraline for the treatment of PTSD in a Japanese clinical setting, and the obtained safety profile was

  17. Effect of sequential application of topical adapalene and clindamycin phosphate in the treatment of Japanese patients with acne vulgaris.

    PubMed

    Kubota, Yasuo; Munehiro, Asuka; Shirahige, Yoshie; Nakai, Kozo; Katsuura, Junko; Moriue, Tetsuya; Murakami, Yumi; Matsunaka, Hiroshi; Yoneda, Kozo

    2012-02-01

    The efficacy of combined therapy with a retinoid and antibiotic for Japanese patients with acne vulgaris remains to be established. Further, maintenance strategies limiting the use of topical retinoids must be identified. The objectives of this study are to determine the efficacy of sequential application of topical adapalene and clindamycin phosphate and to assess the impact of this regimen on patients' quality of life. Sixty-six patients were recruited. The regimen comprised two phases. For the 4-week initial treatment, 1% clindamycin phosphate gel was applied twice daily and 0.1% adapalene gel, once. In the 4-week maintenance phase, patients were randomly assigned to the OD group (adapalene applied once daily) or the TW group (adapalene applied once daily on 2 days per week). The acne severity score, lesion counts, microcomedone count, and sebum amount were measured. Quality of life (QOL) was assessed using Skindex-16. All parameters improved significantly by week 4 of initial treatment. No statistically significant differences were found in the improvement of clinical findings between the groups. All QOL scores improved significantly and did not significantly differ between the groups. Our regimen may enable clinical control of acne in Japanese patients and improve their QOL. For limiting retinoid use, weekly application of adapalene during maintenance is suitable.

  18. Efficacy and Safety of an Orally Administered Selective Prostacyclin Receptor Agonist, Selexipag, in Japanese Patients With Pulmonary Arterial Hypertension.

    PubMed

    Tanabe, Nobuhiro; Ikeda, Satoshi; Tahara, Nobuhiro; Fukuda, Keiichi; Hatano, Masaru; Ito, Hiroshi; Nakayama, Tomotaka; Anzai, Toshihisa; Hashimoto, Akiyoshi; Inoue, Teruo; Kajinami, Kouji; Kihara, Yasuki; Kinoshita, Hideyuki; Kuwahara, Koichiro; Murohara, Toyoaki; Okazaki, Osamu; Sakai, Satoshi; Satoh, Toru; Takeda, Yutaka; Takeishi, Yasuchika; Taniguchi, Mitsugu; Watanabe, Hiroshi; Yamamoto, Takeshi; Yamauchi-Takihara, Keiko; Yoshioka, Koichiro; Sasayama, Shigetake

    2017-08-25

    Selexipag is an orally available prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. In this open-label Phase II trial, the efficacy and safety of selexipag in Japanese patients with pulmonary arterial hypertension (PAH) is examined.Methods and Results:Selexipag was administered at 200 μg twice daily and titrated up to 1,600 μg by increments of 200 μg in 37 subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33 patients comprising the per-protocol set, the pulmonary vascular resistance (PVR; primary endpoint) decreased from 683.2±237.3 to 560.3±238.7 dyn·s/cm(5)(P<0.0001). For the secondary endpoint, the 6-min walk distance (6MWD) increased from 445.0±102.2 to 459.1±112.8 m (P=0.0324); World Health Organization functional class improved in 4 patients (12.1%), and was maintained in 29 patients (87.9%). A decrease in PVR was also shown in patients treated with selexipag, on top of a phosphodiesterase inhibitor and endothelin receptor antagonist. Most of the commonly reported adverse events were consistent with those reported for other PGI2formulations. Thirty-four patients attained the individual maximum tolerated dose (maintenance dose). The efficacy and tolerability of selexipag in Japanese PAH patients was confirmed by improvement in pulmonary hemodynamics, exercise capacity, symptoms. Selexipag is an efficacious treatment option for Japanese PAH patients. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111532].).

  19. Early prediction of blonanserin response in Japanese patients with schizophrenia

    PubMed Central

    Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

    2014-01-01

    Background Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. Methods An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Results Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively. Conclusion Our results suggest that the blonanserin response at week 4 could predict the later response at week 8. PMID:25285009

  20. Early prediction of blonanserin response in Japanese patients with schizophrenia.

    PubMed

    Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

    2014-01-01

    Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively. Our results suggest that the blonanserin response at week 4 could predict the later response at week 8.

  1. EGFR Mutation status in Japanese lung cancer patients: genotyping analysis using LightCycler.

    PubMed

    Sasaki, Hidefumi; Endo, Katsuhiko; Konishi, Akimitsu; Takada, Minoru; Kawahara, Masaaki; Iuchi, Keiji; Matsumura, Akihide; Okumura, Meinoshin; Tanaka, Hisaichi; Kawaguchi, Tomoya; Shimizu, Toshiki; Takeuchi, Hiroshi; Yano, Motoki; Fukai, Ichiro; Fujii, Yoshitaka

    2005-04-15

    Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in approximately 25% of Japanese lung cancer patients. These EGFR mutations are reported to be correlated with clinical response to gefitinib therapy. However, DNA sequencing using the PCR methods described to date is time-consuming and requires significant quantities of DNA; thus, this existing approach is not suitable for a routine pretherapeutic screening program. We have genotyped EGFR mutation status in Japanese lung cancer patients, including 102 surgically treated lung cancer cases from Nagoya City University Hospital and 16 gefitinib-treated lung cancer cases from Kinki-chuo Chest Medical Center. The presence or absence of three common EGFR mutations were analyzed by real-time quantitative PCR with mutation-specific sensor and anchor probes. In exon 21, EGFR mutations (CTG --> CGG; L858R) were found from 8 of 102 patients from Nagoya and 1 of 16 from Kinki. We also detected the deletion mutations in exon 19 from 7 of 102 patients from Nagoya (all were deletion type 1a) and 4 of 16 patients from Kinki (one was type 1a and three were type 1b). In exon 18, one example of G719S mutation was found from both Nagoya and Kinki. The L858R mutation was significantly correlated with gender (women versus men, P < 0.0001), Brinkman index (600 < or = versus 600, P = 0.001), pathologic subtypes (adenocarcinoma versus nonadenocarcinoma, P = 0.007), and differentiation status of the lung cancers (well versus moderately or poorly, P = 0.0439), whereas the deletion mutants were not. EGFR gene status, including the type of EGFR somatic mutation, was correlated with sensitivity to gefitinib therapy. For example, some of our gefitinib-responsive patients had L858R or deletion type 1a mutations. On the other hand, one of our gefitinib-resistant patients had a G719S mutation. Using the LightCycler PCR assay, the EGFR L858R mutation status might correlate with gender, pathologic subtypes, and

  2. Seroprevalence of Cysticercus Antibodies in Japanese Encephalitis Patients in Upper Assam, India: A Hospital Based Study

    PubMed Central

    Mazumdar, Himangshu; Saikia, Lahari

    2016-01-01

    Introduction Co-infection of Japanese Encephalitis (JE) and Cysticercosis is attributed mainly to the common epidemiological features between the two diseases. Not much is known about the clinical implications of one infection over the other. Aim The study aimed at establishing whether JE-Cysticercosis co-infection is prevalent in the Upper Assam districts and to explore additional details about such co-infections both clinically and epidemiologically. Materials and Methods The present study was a retrospective cross-sectional hospital based study conducted between July 2013 and June 2014 and included 272 Acute Encephalitis Syndrome (AES) patients. Out of this, 137 JE positive and 135 non-JE Acute encephalitis patients were taken as cases and controls respectively. The diagnosis of JE and Cysticercosis was established by ELISA. Statistical Analysis EpiInfo ver. 7 was used for statistical analysis. Chi-square was used and p-value < 0.05 was considered to be statistically significant. Results The association of Cysticercosis with JE was found to be statistically significant (14.6%, p = 0.0019) in the cases with reference to the controls (3.7%). Moreover, the co-infections were found to be more common in case of adults (19.32%, p = 0.0360); with males having a greater odds (5.25, p = 0.0008) of harbouring the parasite as compared to females. Conclusion The study proves that the association of Cysticercosis and JE holds true in this region. PMID:27437215

  3. A feasibility study of the clinical effectiveness and cost-effectiveness of individual cognitive behavioral therapy for panic disorder in a Japanese clinical setting: an uncontrolled pilot study.

    PubMed

    Seki, Yoichi; Nagata, Shinobu; Shibuya, Takayuki; Yoshinaga, Naoki; Yokoo, Mizue; Ibuki, Hanae; Minamitani, Noriko; Kusunoki, Muga; Inada, Yasushi; Kawasoe, Nobuko; Adachi, Soichiro; Yoshimura, Kensuke; Nakazato, Michiko; Iyo, Masaomi; Nakagawa, Akiko; Shimizu, Eiji

    2016-10-07

    In Japan, cognitive behavioral therapy (CBT) for panic disorder (PD) is not well established. Therefore, a feasibility study of the clinical effectiveness and cost-effectiveness of CBT for PD in a Japanese clinical setting is urgently required. This was a pilot uncontrolled trial and the intervention consisted of a 16-week CBT program. The primary outcome was Panic Disorder Severity Scale (PDSS) scores. Quality of life was assessed using the EuroQol's EQ-5D questionnaire. Assessments were conducted at baseline, 8 weeks, and at the end of the study. Fifteen subjects completed outcome measures at all assessment points. At post-CBT, the mean reduction in PDSS scores from baseline was -6.6 (95 % CI 3.80 to -9.40, p < 0.001) with a Cohen's d = 1.77 (95 % CI 0.88-2.55). Ten (66.7 %) participants achieved a 40 % or greater reduction in PDSS. By calculating areas under the curve for EQ-5D index changes, we estimated that patients gained a minimum of 0.102 QALYs per 1 year due to the CBT. This study demonstrated that individual CBT for PD may be useful in Japanese clinical settings but further randomized control trials are needed. UMIN-CTR UMIN000022693 (retrospectively registered).

  4. Effects of vermilion height on lip esthetics in Japanese and Korean orthodontists and orthodontic patients.

    PubMed

    Ioi, Hideki; Kang, Sangwook; Shimomura, Takahiro; Kim, Seong-Sik; Park, Soo-Byung; Son, Woo-Sung; Takahashi, Ichiro

    2014-03-01

    To evaluate the influence of vermilion height on the assessment of lip attractiveness by Japanese and Korean orthodontists and orthodontic patients. Vermilion heights were modified by increasing or decreasing the vermilion height in 1.0-mm increments from -3.0 mm to 3.0 mm with reference to an average vermilion height. Participants ranged from 15 to 29 years of age and comprised 29 Japanese and 25 Korean orthodontists and 96 Japanese and 72 Korean orthodontic patients. They all rated the attractiveness of seven images with altered vermilion height using a visual analog scale. Across the participant groups, there were significant differences in the median esthetic scores for the seven vermilion height levels tested. The Japanese and Korean raters assigned the highest scores to the average vermilion height and assigned the lowest scores to the +3-mm increased vermilion height. The ranges of vermilion height preferred by orthodontists were found to be within the ranges preferred by orthodontic patients when evaluating the preferences in lip esthetics by country. We conclude that the -1-mm to +1-mm range for the average vermilion height is considered attractive for lips for both Japanese and Korean people.

  5. Relations of nutritional intake to age, sex and body mass index in Japanese elderly patients with type 2 diabetes: the Japanese Elderly Diabetes Intervention Trial.

    PubMed

    Yoshimura, Yukio; Kamada, Chiemi; Takahashi, Keiko; Kaimoto, Tae; Iimuro, Satoshi; Ohashi, Yasuo; Araki, Atsushi; Umegaki, Hiroyuki; Sakurai, Takashi; Ito, Hideki

    2012-04-01

    To determine the status of nutritional intake in elderly Japanese patients with type 2 diabetes aged 65 years or older, and to clarify relations of nutritional intake to age, sex and body mass index (BMI). Clinical parameters and nutritional intake were investigated and compared in 912 (417 men, 495 women) elderly Japanese patients with type 2 diabetes registered to the Japanese Elderly Diabetes Intervention Trial. The mean daily energy intake of patients was 1802 kcal in men and 1661 kcal in women, respectively. The energy intakes per kilogram of standard bodyweight in both sexes and the energy intakes per kilogram of present bodyweight in men increased significantly with age. The protein : fat : carbohydrate (PFC) energy ratio (%E) was 15.2:25.4:59.5 in men, and 15.7:25.8:58.6 in women, respectively. Grain, oil, alcohol and soft drink intakes were higher in men than in women. Potato, fruit and green vegetable intakes were higher in women than in men. Fruit intake showed a significant age-related increase in men. In women, there was an age-related significant decrease of meat intake. An increase of BMI correlated with a significant increase in bodyweight, waist circumference, hip circumference, waist-to-hip ratio, triglycerides and diastolic blood pressure. The mean energy intake of three BMI groups, lean (BMI < 18.5 kg/m(2)), normal (18.5 kg/m(2)

  6. Lack of KIR4.1 autoantibodies in Japanese patients with MS and NMO

    PubMed Central

    Higuchi, Osamu; Sakai, Waka; Maeda, Yasuhiro; Niino, Masaaki; Takahashi, Toshiyuki; Fukazawa, Toshiyuki; Kikuchi, Seiji; Fujihara, Kazuo; Matsuo, Hidenori

    2016-01-01

    Objectives: To examine anti-KIR4.1 antibodies by 2 different assays in Japanese patients with multiple sclerosis (MS) or neuromyelitis optica (NMO). Methods: One hundred sixty serum samples from 57 patients with MS, 40 patients with NMO/NMO spectrum disorder (NMOSD), and 50 healthy controls (all were Japanese) were tested with ELISA using a synthetic peptide of the first extracellular portion of human KIR4.1. In addition, we attempted to detect anti-KIR4.1 immunoglobulin G in the serum by the luciferase immunoprecipitation systems (LIPS) with the full length of human KIR4.1 produced in a human cell line, which is highly sensitive to single or multiple epitopes. Results: We failed to detect antibodies to the peptide fragment KIR4.183–120 in any case of MS and NMO/NMOSD using ELISA. Antibodies to the recombinant full length of KIR4.1 protein were detected in only 2 patients with MS and none in the patients with NMO/NMOSD by the LIPS assay. Conclusions: We developed 2 different methods (ELISA and LIPS) to measure autoantibodies to KIR4.1 in serum. We detected anti-KIR4.1 immunoglobulin G at a very low frequency in Japanese patients with MS or NMO/NMOSD. Serologic testing for human KIR4.1-specific antibodies is unlikely to improve the diagnosis of MS or NMO/NMOSD in Japanese patients. PMID:27489866

  7. Diagnosis and treatment of TMA based on Japanese clinical guides.

    PubMed

    Wada, Hideo; Hasegawa, Kei; Watanabe, Maki

    Patients with thrombotic microangiopathies (TMAs), which include thrombotic thrombocytopenic purpura (TTP), atypical hemolytic uremic syndrome (aHUS), and Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS), exhibit multiple symptoms. These include thrombocytopenia (platelet count <15×10(4)/µl), microangiopathic hemolytic anemia (hemoglobin <10 g/dl), and organ damage, such as renal dysfunction or neurological abnormalities. Guidelines for the management of TTP, aHUS, and STEC-HUS have been published. Diagnosis of TTP, STEC-HUS, or aHUS requires ADAMTS13 activity <10%, the detection of STEC or Shiga toxins, or a genetic analysis to investigate the complement regulatory system, respectively. In the established management of TMAs, fresh frozen plasma is used for congenital TTP to supplement ADAMTS13. Plasma exchange (PE) is used in acquired TTP (ATTP) to remove inhibitors and replace ADAMTS13. Steroid therapy is administered in ATTP to suppress inhibitor production, and rituximab is administered in ATTP without response to PE or with high titers of ADAMTS13 inhibitors. Eculizumab, a monoclonal antibody for complement protein 5, is used for the treatment of aHUS. Supportive therapy is required for some TMAs, particularly STEC-HUS, but platelet transfusion is generally contraindicated for other TMAs, such as TTP. Treatments should be administered in accordance with these guidelines to improve the outcome of TMAs.

  8. Prevalence of nonalcoholic steatohepatitis in Japanese patients with morbid obesity undergoing bariatric surgery.

    PubMed

    Seki, Yosuke; Kakizaki, Satoru; Horiguchi, Norio; Hashizume, Hiroaki; Tojima, Hiroki; Yamazaki, Yuichi; Sato, Ken; Kusano, Motoyasu; Yamada, Masanobu; Kasama, Kazunori

    2016-03-01

    Patients with morbid obesity selected for bariatric surgery have a high prevalence of nonalcoholic steatohepatitis (NASH); however, the incidence is varied and depends on race. The prevalence of NASH in obese Japanese patients is unknown. We evaluated the prevalence of NASH in a prospective cohort of Japanese patients with morbid obesity. From October 2009 to July 2011, consecutive patients requiring bariatric surgery underwent a liver biopsy during the operation. The indications for bariatric surgery followed the guidelines of the Asia-Pacific Metabolic and Bariatric Surgery Society. One hundred two patients (55 males and 47 females, age 42.7 ± 10.7 years) were analyzed. The mean body mass index was 42.1 ± 8.2 kg/m(2). Among the 102 patients, 84 patients (82.4%) had nonalcoholic fatty liver disease and 79 patients (77.5%) had NASH. The grading and staging of NASH by Brunt's classification were as follows: grade 0 steatosis, one patient; grade 1 steatosis, 35 patients; grade 2 steatosis, 32 patients; grade 3 steatosis, 11 patients; stage 1 fibrosis, 25 patients; stage 2 fibrosis, 38 patients; stage 3 fibrosis, 16 patients, stage 4 fibrosis, no patients. The body weight, waist-hip ratio, visceral fat area, and aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, fasting plasma glucose, fasting plasma insulin, C peptide, hemoglobin A1c, and homeostasis model assessment insulin resistance levels were significantly elevated in the NASH group in comparison with the non-NASH group. The platelet count was significantly decreased in the NASH group. The waist-hip ratio and the alanine aminotransferase, fasting plasma glucose, and homeostasis model assessment insulin resistance levels were found to be independent predictors of NASH in a multivariate analysis. The prevalence of NASH was 77.5% in this prospective Japanese cohort. The prevalence of NASH in Japanese morbidly obese patients was extremely high, and early intervention should be

  9. Efficacy of antiresorptive agents for preventing fractures in Japanese patients with an increased fracture risk: review of the literature.

    PubMed

    Iwamoto, Jun; Sato, Yoshihiro; Takeda, Tsuyoshi; Matsumoto, Hideo

    2012-03-01

    The aim of the present review was to clarify the efficacy of currently available potent antiresorptive agents for preventing fractures in Japanese patients with an increased fracture risk. PubMed was used to search the literature for randomized controlled trials (RCTs), with the following search terms: fracture, etidronate, alendronate, risedronate, minodronate, raloxifene, bazedoxifene and Japan. The inclusion criteria were papers written in English, ≥50 subjects per group and a study period of ≥1 year. Fourteen RCTs met these criteria. The efficacy of antiresorptive agents for preventing vertebral, nonvertebral and hip fractures was investigated. There was evidence that raloxifene reduced the incidence of clinical vertebral fractures, while etidronate, alendronate and minodronate (but not bazedoxifene) reduced the incidence of morphometric vertebral fractures in patients with postmenopausal or involutional osteoporosis. Head-to-head trials showed that alendronate and raloxifene had similar efficacy for preventing vertebral fractures in patients with postmenopausal osteoporosis, while risedronate was not inferior to etidronate for reducing the incidence of morphometric vertebral fractures in patients with involutional osteoporosis. Alendronate reduced the incidence of hip fractures in patients with Parkinson's disease, and risedronate reduced the incidence of nonvertebral fractures and hip fractures in patients with Alzheimer's disease or stroke. In conclusion, the present review confirmed the efficacy of etidronate, minodronate and raloxifene for the prevention of vertebral fractures, the efficacy of alendronate for vertebral and hip fractures, and the efficacy of risedronate for vertebral, nonvertebral and hip fractures in Japanese patients with an increased fracture risk.

  10. Phase I study of TAC-101, an oral synthetic retinoid, in Japanese patients with advanced hepatocellular carcinoma.

    PubMed

    Okusaka, Takuji; Ueno, Hideki; Ikeda, Masafumi; Takezako, Yoriko; Morizane, Chigusa

    2012-08-01

    Preclinical models have shown that TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid), an oral synthetic retinoid, has antitumor activity in hepatocellular carcinoma (HCC). We conducted a phase I study in Japanese patients with advanced HCC to examine the pharmacokinetics, recommended dose, safety, and efficacy of TAC-101. The administered dose of TAC-101 was 10 mg/day in four patients (level 1), 20 mg/day in six (level 2), and 30 mg/day in three (level 3). There was no dose-limiting toxicity at level 1. Only one patient each had dose-limiting toxicity at level 2 (grade 2 fatigue, recovery requiring eight or more consecutive days of rest) and at level 3 (grade 3 splenic vein thrombosis). Level 3 (30 mg/day) was considered the maximum tolerated dose and 20 mg/day the recommended dose by a panel of medical experts, placing maximum emphasis on safety. The most frequent adverse events were fatigue, headache, and dermal symptoms such as rash. Pharmacokinetic parameters in Japanese patients with HCC were similar to those in patients in the United States, most of whom were Caucasian. Although no patient had a complete or partial response, the disease control rate was 38.5%. In conclusion, the recommended dose of TAC-101 for patients with HCC is 20 mg/day. TAC-101 had an acceptable toxicity profile, warranting further evaluation in clinical trials.

  11. Clinical Anatomy of the Liver: Review of the 19th Meeting of the Japanese Research Society of Clinical Anatomy

    PubMed Central

    Sakamoto, Yoshihiro; Kokudo, Norihiro; Kawaguchi, Yoshikuni; Akita, Keiichi

    2017-01-01

    Precise clinical knowledge of liver anatomy is required to safely perform a hepatectomy, for both open and laparoscopic surgery. At the 19th meeting of the Japanese Research Society of Clinical Anatomy (JRSCA), we conducted special symposia on essential issues of liver surgery, such as the history of hepatic segmentation, the glissonean pedicle approach, application of 3-D imaging simulation and fluorescent imaging using indocyanine green solution, a variety of segmentectomies including caudate lobectomy, the associating liver partition and portal vein embolization for stage hepatectomy and harvesting liver grafts for living donor liver transplantation. The present review article provides useful information for liver surgeons and anatomic researchers. PMID:28275581

  12. Nilotinib as frontline therapy for patients with newly diagnosed Ph+ chronic myeloid leukemia in chronic phase: results from the Japanese subgroup of ENESTnd.

    PubMed

    Nakamae, Hirohisa; Shibayama, Hirohiko; Kurokawa, Mineo; Fukuda, Tetsuya; Nakaseko, Chiaki; Kanda, Yoshinobu; Nagai, Tadashi; Ohnishi, Kazunori; Maeda, Yasuhiro; Matsuda, Akira; Amagasaki, Taro; Yanada, Masamitsu

    2011-05-01

    Recent results from the phase 3 ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) study have demonstrated superiority of nilotinib over imatinib for the treatment of newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase (CML-CP). Here, we report results from the Japanese subset of patients in ENESTnd, and assess whether results in this subpopulation are consistent with the overall study population. Seventy-nine Japanese patients with CML-CP were randomized to receive nilotinib 300 mg twice daily (BID) (n = 30), nilotinib 400 mg BID (n = 24) or imatinib 400 mg once daily (QD) (n = 25). Major molecular response rates at 12 months, the primary endpoint, were at least twice as high for nilotinib 300 mg BID (57%) and nilotinib 400 mg BID (50%) compared with imatinib 400 mg QD (24%). No patient on nilotinib progressed, while one patient progressed on imatinib. Both drugs were generally well tolerated and discontinuations due to adverse events were comparable among treatment arms. The results in the subpopulation of Japanese patients from ENESTnd closely mirror the results of the overall population, and support the use of nilotinib at 300 mg BID in Japanese patients with newly diagnosed CML-CP.

  13. Model-based determination of abatacept exposure in support of the recommended dose for Japanese rheumatoid arthritis patients.

    PubMed

    Hasegawa, Mayumi; Imai, Yasuhiko; Hiraoka, Masaki; Ito, Kiyomi; Roy, Amit

    2011-12-01

    The objective of this study was to provide support for a body weight-tiered dosing regimen by characterizing abatacept pharmacokinetics (PK) and the relationship between exposure and the ACR20 (American College of Rheumatology criteria for 20% improvement) response in Japanese patients with rheumatoid arthritis (RA). A population PK model was developed using NONMEM with 2,535 samples from 344 Japanese RA patients in two clinical trials. The exposure-response relationship was characterized using a Generalized Estimating Equation (GEE) logistic regression model, with time-varying actual trough concentrations and ACR20 responder rates over 6 months in a randomized, placebo-controlled phase 2 trial for stable methotrexate. Abatacept exposure was well characterized using a linear, two-compartment model, in which body weight and the empirically calculated glomerular filtration rate were significant covariates for clearance. The ACR20 response model was developed by examining the quasi-likelihood information criterion, and the cumulative logit in the final model was specified by the log-transformed trough concentration. The predicted ACR20 responder rate was consistent with the actual values in the clinical trial and this model revealed trough concentrations higher than the recommended body weight-tiered dose are unlikely to result in substantial increases in clinical efficacy. Considering that ACR20 is a longitudinal binary variable and the response to RA treatment is delayed, the GEE model was useful for predicting the probability of an ACR20 response. In conclusion, the same dosing regimen as non-Japanese patients is recommended because a body weight-tiered dosing regimen achieves similar exposures across the wide range of body weight.

  14. Hemoglobin maintenance and dosing strategies using intravenous continuous erythropoietin receptor activator in Japanese hemodialysis patients.

    PubMed

    Hirai, Takayuki; Nishizawa, Yoshiko; Nakazono, Hiroshi; Asai, Mariko; Yamashita, Hideki; Sasaki, Ayako; Yamashita, Tetsumasa; Yamashita, Kazuomi; Shigemoto, Kenichiro; Harada, Satoru; Mizuiri, Sonoo

    2013-10-01

    Methoxy polyethylene glycol-epoetin beta, a continuous erythropoietin receptor activator (CERA), is reported to be effective in managing renal anemia but there is little data about CERA in Japan. This study aimed to ascertain the effects of CERA in Japanese hemodialysis patients and the appropriate starting dose of CERA when switching from other erythropoiesis-stimulating agents. We switched 61 stable hemodialysis patients to 4-weekly intravenous CERA, from either epoetin beta (rHuEPO) or darbepoetin alpha (DA). When determining the initial dose of CERA, we used guidelines recommended by the Japanese supplier for switching from rHuEPO, but for DA we based the CERA dose on European reports, because no Japanese guidelines exist. Fifty-two patients completed the 28-week study. Hemoglobin was maintained within the target range (10.0-12.0 g/dL). The required CERA dose decreased over the 28 weeks. The hemoglobin level and CERA dose stabilized faster when switching from DA. CERA showed similar efficacy in diabetic and non-diabetic patients. The effect of CERA is similar regardless of whether patients switch from low- or high-dose erythropoiesis-stimulating agents. In conclusion, CERA is effective for Japanese hemodialysis patients at a lower dose than expected. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

  15. Panitumumab in Japanese patients with unresectable colorectal cancer: a post-marketing surveillance study of 3085 patients.

    PubMed

    Boku, Narikazu; Sugihara, Kenichi; Kitagawa, Yuko; Hatake, Kiyohiko; Gemma, Akihiko; Yamazaki, Naoya; Muro, Kei; Hamaguchi, Tetsuya; Yoshino, Takayuki; Yana, Ikuo; Ueno, Hiroshi; Ohtsu, Atsushi

    2014-03-01

    Panitumumab was approved in Japan in April 2010 for the treatment of Kirsten rat sarcoma-2 virus oncogene wild-type unresectable and recurrent colorectal cancer. We conducted a post-marketing surveillance study to evaluate the safety and effectiveness of panitumumab. After panitumumab was commercially available in Japan, all patients to be treated with panitumumab were enrolled. Data on baseline characteristics, treatment outcome, and incidence and severity of adverse drug reactions were collected. In total, 3091 patients were registered. In the safety analysis set (n = 3085), panitumumab was administered as monotherapy (40.7%) or combination therapy (59.4%). The median treatment duration was 113 days (range: 1-559 days), and 451 (14.6%) patients received panitumumab for ≥10 months. The overall incidence rate of adverse drug reactions was 84.1%, and the most common adverse drug reaction was skin disorders (78.4%). The incidence rates (all grades) of interstitial lung disease, infusion reaction, electrolyte abnormalities and cardiac disorders were 1.3% (mortality rate: 0.6%), 1.5, 19.3 and 0.2%, respectively. The median survival time of patients treated with panitumumab monotherapy as the third-line, or later, therapy was 10.3 months. This post-marketing survey in clinical practice confirmed the safety and effectiveness of panitumumab. The benefit/risk balance for panitumumab in Japanese patients with unresectable colorectal cancer remains favorable.

  16. Novel compound heterozygous mutations identified by whole exome sequencing in a Japanese patient with geroderma osteodysplastica.

    PubMed

    Takeda, Ryojun; Takagi, Masaki; Shinohara, Hiroyuki; Futagawa, Hiroshi; Narumi, Satoshi; Hasegawa, Tomonobu; Nishimura, Gen; Yoshihashi, Hiroshi

    2017-08-12

    Geroderma osteodysplastica (GO) is a subtype of cutis laxa syndrome characterized by congenital wrinkly skin, a prematurely aged face, extremely short stature, and osteoporosis leading to recurrent fractures. GO exhibits an autosomal recessive inheritance pattern and is caused by loss-of-function mutations in GORAB, which encodes a protein important for Golgi-related transport. Using whole exome sequencing, we identified novel compound heterozygous nonsense mutations in the GORAB in a GO patient. The patient was a 14-year-old Japanese boy. Wrinkled skin and joint laxity were present at birth. At 1 year of age, he was clinically diagnosed with cutis laxa syndrome based on recurrent long bone fractures and clinical features, including wrinkled skin, joint laxity, and a distinctive face. He did not show retarded gross motor and cognitive development. At 11 years of age, he was treated with oral bisphosphonate and vitamin D owing to recurrent multiple spontaneous fractures of the vertebral and extremity bones associated with a low bone mineral density (BMD). Bisphosphonate treatment improved his BMD and fracture rate. Whole exome sequencing revealed two novel compound heterozygous nonsense mutations in the GORAB gene (p.Arg60* and p.Gln124*), and the diagnosis of GO was established. GO is a rare connective tissue disorder. Approximately 60 cases have been described to date, and this is the first report of a patient from Japan. Few studies have reported the effects of bisphosphonate treatment in GO patients with recurrent spontaneous fractures. Based on this case study, we hypothesize that oral bisphosphonate and vitamin D are effective and safe treatment options for the management of recurrent fractures in GO patients. It is important to establish a precise diagnosis of GO to prevent recurrent fractures and optimize treatment plans. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Pharmacokinetics of oxycodone after intravenous and subcutaneous administration in Japanese patients with cancer pain.

    PubMed

    Kokubun, Hideya; Yoshimoto, Tetsusuke; Hojo, Minoru; Fukumura, Kazuya; Matoba, Motohiro

    2014-12-01

    ABSTRACT In Japan, Oxycodone hydrochloride injection formulation has been approved in 2012. However, its pharmacokinetics has been poorly studied. The aim of this study is to evaluate the pharmacokinetics of oxycodone after intravenous and subcutaneous administration of oxycodone hydrochloride injection in Japanese patients with cancer pain. Noncompartmental analysis and population pharmacokinetic analysis were performed. We conducted a multicenter open-label study of oxycodone hydrochloride administered as constant infusion with the dose titrated individually according to the pain intensity in patients with cancer pain. Pharmacokinetic parameters for plasma oxycodone and its metabolites were estimated using pharmacokinetics of oxycodone was evaluated using a total of 344 plasma concentrations obtained from 89 patients. The estimated geometric mean clearance (CL) of oxycodone was 24.3 L per hour after constant intravenous infusion and 29.5 L per hour after constant subcutaneous infusion, respectively. Population pharmacokinetic analysis indicated that body surface area was the influencing factor on CL and there were no pharmacokinetic differences for CL between intravenous and subcutaneous infusion. These results provide important information for the clinical use of oxycodone injection.

  18. One year efficacy and safety of lanthanum carbonate for hyperphosphatemia in Japanese chronic kidney disease patients undergoing hemodialysis.

    PubMed

    Shigematsu, Takashi

    2010-02-01

    Lanthanum carbonate is a non-calcium-based phosphate binder for hyperphosphatemia in patients with chronic kidney disease (CKD). The efficacy and safety of lanthanum carbonate (LaC) on hyperphosphatemia in patients has been well documented in clinical trials in Western countries and recent relatively short-term clinical trials in Japan. Evidence supporting its safety and efficacy in Japanese patients for longer-term treatment is now desired for clinical practice. A non-controlled, open-label, multicenter, one year study of LaC to assess safety and its effect on the levels of serum phosphate, serum calcium and parathyroid hormone was performed with Japanese dialysis patients. Lanthanum carbonate was administered to patients at variable doses for a period of 46-52 weeks. Evaluation of the safety and efficacy of LaC in reducing serum phosphate was performed, in addition to extensive and systematic monitoring of the laboratory parameters related to bone turnover and cardiac health. A significant reduction in the serum phosphate level was demonstrated throughout the treatment period (P < 0.05), without any increase in the frequency or severity of drug-related adverse events such as vomiting, nausea, and stomach discomfort. There was no clinically relevant change in vital signs, or electrocardiograms for a period. The profiles for parathyroid hormone, bone alkaline phosphates, and osteocalcin were stable in the patients concomitantly treated with vitamin D. This study provides further evidence that the administration of LaC over a period of one year is safe and effective for the reduction of serum phosphate levels in CKD patients undergoing hemodialysis.

  19. Clinical evaluation of body fat percentage in 11,833 Japanese measured by air displacement plethysmograph.

    PubMed

    Miyatake, Nobuyuki; Takenami, Sumiko; Kawasaki, Yuriko; Kunihashi, Yumiko; Nishikawa, Hidetaka; Numata, Takeyuki

    2005-07-01

    Body fat percentage is commonly used for assessing body composition. We investigated the body fat percentage in Japanese subjects measured by air displacement plethysmograph (ADP) termed BOD POD. Cross-sectional clinical investigation study. We used data of 11,833 Japanese subjects aged 20-79 years [body mass index (BMI): 23.2+/-3.7 kg/m2]. Body fat percentage was evaluated by BOD POD. Anthropometric parameters such as height, weight, BMI, waist circumference and hip circumference were also measured. Mean values of body fat percentage measured by BOD POD were 24.5+/-6.6% in men and 31.1+/-7.1% in women, mean values were also calculated as classified into aged groups in normal weight subjects. Body fat percentage was significantly correlated with BMI and 25.1% of men and 34.6% of women corresponded to 25 kg/m2 in BMI. Mean value of body fat percentage in normal weight Japanese subjects was revealed. In addition, the level of 25% in men and 35% in women corresponded to 25 kg/m2 of BMI.

  20. The first Japanese patient with variant Creutzfeldt-Jakob disease (vCJD).

    PubMed

    Shinde, Akiyo; Kunieda, Takenobu; Kinoshita, Yoshimi; Wate, Reika; Nakano, Satoshi; Ito, Hidefumi; Yamada, Masahito; Kitamoto, Tetsuyuki; Nakamura, Yosikazu; Matsumoto, Sadayuki; Kusaka, Hirofumi

    2009-12-01

    Eleven years after a brief visit to some European countries, a 48-year-old Japanese man developed writing difficulty, irritability and general fatigue. Then he complained of dysesthetic pains in his legs, for which benzodiazepines were prescribed. However, at the time pulvinar sign was retrospectively confirmed on brain MRI. Eighteen months after the onset, his gait became ataxic with rapid deterioration of mental status over the following several months. Thirty-one months after the onset, he became akinetic and mute with periodic synchronous discharges on EEG, and died at the age of 51. The total clinical course was approximately 43 months. Pathological examination revealed the characteristic alterations of spongiform encephalopathy, severe in the thalamus, moderate but widely spread in the cerebral cortices, and moderate in the cerebellum. Abundant amyloid plaques were easily identified in the cerebral cortex and the cerebellum on HE staining. Immunohistochemistry for abnormal prion protein (PrP(sc)) confirmed amyloid plaques in several forms, such as florid, uni- and multi-centric plaques as well as perineuronal and periaxonal deposits in the basal ganglia and synaptic patterns in the thalami. A Western blotting study identified type 2B protease-resistant PrP. This is the first Japanese patient who was definitely diagnosed as variant Creutzfeldt-Jakob disease (vCJD). The pathological findings were similar to those of previous reports of vCJD in the UK. However, the changes were much more severe both in degree and distribution, probably due to a longer duration of the illness than those in the UK.

  1. Family history, body mass index and survival in Japanese patients with stomach cancer: a prospective study.

    PubMed

    Minami, Yuko; Kawai, Masaaki; Fujiya, Tsuneaki; Suzuki, Masaki; Noguchi, Tetsuya; Yamanami, Hideaki; Kakugawa, Yoichiro; Nishino, Yoshikazu

    2015-01-15

    Family history and nutritional status may affect the long-term prognosis of stomach cancer, but evidence is insufficient and inconsistent. To clarify the prognostic factors of stomach cancer, we conducted a prospective study of 1,033 Japanese patients with histologically confirmed stomach cancer who were admitted to a single hospital between 1997 and 2005. Family history of stomach cancer and pretreatment body mass index (BMI) were assessed using a self-administered questionnaire. Clinical data were retrieved from a hospital-based cancer registry. All patients were completely followed up until December, 2008. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated according to family history in parents and siblings and BMI category. During a median follow-up of 5.3 years, 403 all-cause and 279 stomach cancer deaths were documented. Although no association with family history was observed in the patients overall, analysis according to age group found an increased risk of all-cause death associated with a history in first degree relatives (HR = 1.61, 95% CI: 0.93-2.78, p = 0.09) and with a parental history (HR = 1.86, 95% CI: 1.06-3.26) among patients aged under 60 years at diagnosis. BMI was related to all-cause and stomach cancer death among patients aged 60 and over, showing a J-shaped pattern (HR of all-cause death = 2.28 for BMI < 18.5; HR = 1.61 for 25 ≤ vs. ≥ 23.0 to < 25.0 kg/m(2)). A family history of stomach cancer, especially parental history, may affect mortality among younger stomach cancer patients, whereas nutritional status may be a prognostic factor in older patients. © 2014 UICC.

  2. Effects of ward rotation on subsequent transition processes of Japanese clinical nurses.

    PubMed

    Fujino, Mitsuku; Nojima, Yoshiko

    2005-03-01

    The purpose of this study was to examine the experience of Japanese clinical nurses undertaking a ward rotation in a general hospital, and its effects on subsequent processes relating to: (i) perception of ward rotation; (ii) reactions to the ward transition process; and (iii) outcomes of ward rotation. In-depth interviews were conducted with 21 Japanese clinical nurses who had an average of 8.8 years (SD = 5.50) clinical experience. Findings indicated that participants experienced role overload, role incongruity and/or role underload, role overqualification, or role ambiguity in the new environment. These role stresses created critical emotional distress during the transition process. The high desire for career development facilitated the transition process, while lack of preparation inhibited the transition process. To facilitate smooth transition, well-prepared and structured supports based on reliable interpersonal relationships are necessary. The findings offer significant cues for effective ward rotation programs. The implication for nursing administrators is that appropriate ward rotations enhance confidence and promote effective role development in the new clinical setting.

  3. Human leukocyte antigen DR1 in Japanese and Turkish patients with schizophrenia.

    PubMed

    Ozcan, M Erkan

    2006-05-01

    The main focus of this review has been to discuss the probable causes of the higher frequency of HLA DR1 antigen in patients with schizophrenia from Japan and Turkey, and also to see whether there was an impact of belonging to the Ural-Altaic language group. A general medline search on the terms HLA and schizophrenia was used as the method to determine HLA studies in patients with schizophrenia. Most of the findings were inconsistent regarding the increased or decreased frequencies of different Class I and II antigens. However, there were interesting results, which have been consistently repeated in several Japanese studies and in a Turkish study. HLA DR1 antigen was statistically significantly increased in Japanese and Turkish patients with schizophrenia. As Japanese and Turkish languages belong to the Ural-Altaic language group, HLA DR1 antigen might have a specific association with schizophrenia in Japanese and Turkish patients. Searching the frequency of HLA DR1 antigen in patients with schizophrenia in other members of Ural-Altaic language group is necessary to support this hypothesis. Other language groups (e.g. Indo-European) should be assessed as well.

  4. Effect of high-fat meal intake on the pharmacokinetic profile of ivermectin in Japanese patients with scabies.

    PubMed

    Miyajima, Atsushi; Hirota, Takashi; Sugioka, Akihito; Fukuzawa, Masao; Sekine, Mari; Yamamoto, Yosuke; Yoshimasu, Takashi; Kigure, Akira; Anata, Taichi; Noguchi, Wataru; Akagi, Keita; Komoda, Masayo

    2016-09-01

    Ivermectin (IVM) is used as an anthelmintic agent in many countries. To evaluate the effect of high-fat (HF) meal intake on the pharmacokinetics of IVM, a clinical trial was conducted in Japanese patients with scabies. The patients were administrated Stromectol(®) tablets in the fasted state, and after 1 week they were also administrated it after a HF meal (fed state). After the administration, IVM concentrations in plasma and the stratum corneum were determined. The geometric mean of fed/fasted ratio of area under IVM concentration-time curve (AUC) in plasma was 1.25 (90% confidence interval, 1.09-1.43), suggesting the tendency to increased absorption after a HF meal. The fed/fasted ratio of the maximum IVM concentration in the stratum corneum was well correlated with that in plasma. In addition, no serious adverse events were observed during the trial, while a mild increase of aspartate aminotransferase and alanine aminotransferase activity in plasma was observed under the fed state in two patients. The mean AUC of IVM in plasma of those two patients were approximately threefold higher than that of the other patients at that time. On the other hand, the treatment success rate was 76.9% at 7 days after the second administration, which was comparable with the expected level. The present study not only demonstrates that HF meal intake increases the IVM concentration in plasma and the stratum corneum in Japanese patients with scabies, but also suggests the possibility that HF meals increase the risk of hepatic dysfunction by the increased exposure of IVM. © 2016 Japanese Dermatological Association.

  5. Phase III randomized trial of toremifene versus tamoxifen for Japanese postmenopausal patients with early breast cancer.

    PubMed

    Kimura, Morihiko; Tominaga, Takeshi; Kimijima, Izo; Takatsuka, Yuichi; Takashima, Shigemitsu; Nomura, Yasuo; Kasumi, Fujio; Yamaguchi, Akihiro; Masuda, Norikazu; Noguchi, Shinzaburo; Eshima, Nobuoki

    2014-05-01

    Toremifene, a selective estrogen receptor modulator, is used as adjuvant therapy for postmenopausal patients with breast cancer in Japan. For Japanese patients, however, only limited data are available on the efficacy and safety profile of toremifene. To establish the long term efficacy and safety of toremifene for Japanese patients, we conducted a prospective, multicenter, randomized phase III trial comparing toremifene and tamoxifen. The subjects were postmenopausal Japanese patients who had undergone surgery for node-negative breast cancer. Toremifene or tamoxifen was administered for 2 years. The primary endpoint was demonstration of the non-inferiority of toremifene compared with tamoxifen in respect of 5-year survival. Secondary endpoints were cumulative overall survival, cumulative disease-free survival, effects on lipid profiles, and adverse events. A total of 253 patients were enrolled. The baseline characteristics of the two treatment groups were well-balanced. Median follow-up was 66.5 months. Five-year survival was similar for toremifene and tamoxifen (97.0 vs. 96.9 %; 90 % confidence interval -3.9 to 4.1), indicating that toremifene is not inferior to tamoxifen for postmenopausal Japanese patients with early breast cancer. Cumulative overall survival and cumulative disease-free survival were also very similar for toremifene and tamoxifen (97.5 vs. 97.3 %, log-rank test P = 0.9458; 88.4 vs. 90.6 %, log-rank test P = 0.3359, respectively). Adverse events in both groups were similar and mostly mild or moderate. Thus, both are equally effective and well tolerated. Our results suggest that the efficacy and safety of toremifene and tamoxifen are equivalent for postmenopausal Japanese patients with early breast cancer.

  6. Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients

    PubMed Central

    Tamura, Yasuhiro; Funaki, Yasushi; Izawa, Shinya; Iida, Akihito; Yamaguchi, Yoshiharu; Adachi, Kazunori; Ogasawara, Naotaka; Sasaki, Makoto; Kaneko, Hiroshi; Kasugai, Kunio

    2015-01-01

    AIM: To investigate the pathophysiology of functional heartburn (FH) in Japanese patients. METHODS: A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria. RESULTS: Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences. CONCLUSION: Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them. PMID:25945016

  7. Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients.

    PubMed

    Tamura, Yasuhiro; Funaki, Yasushi; Izawa, Shinya; Iida, Akihito; Yamaguchi, Yoshiharu; Adachi, Kazunori; Ogasawara, Naotaka; Sasaki, Makoto; Kaneko, Hiroshi; Kasugai, Kunio

    2015-04-28

    To investigate the pathophysiology of functional heartburn (FH) in Japanese patients. A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria. Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences. Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them.

  8. Phase-1 study of abiraterone acetate in chemotherapy-naïve Japanese patients with castration-resistant prostate cancer

    PubMed Central

    Matsubara, Nobuaki; Uemura, Hiroji; Fukui, Iwao; Niwakawa, Masashi; Yamaguchi, Akito; Iizuka, Koho; Akaza, Hideyuki

    2014-01-01

    Persistent androgen synthesis under castration status in adrenal gland, testes and tumor cells is thought to be one of the major causes of development and progression of castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA), the prodrug of abiraterone, which is an inhibitor of androgen synthesis enzymes, was evaluated for pharmacokinetics, pharmacodynamics, preliminary efficacy and safety in Japanese patients with CRPC in a phase-1, open-label and dose-escalation study. Chemotherapy-naïve Japanese CRPC patients (N = 27) received one of four AA daily doses (250 mg [n = 9], 500 mg [n = 6], 1000 [1 h premeal] mg [n = 6] and 1000 [2 h postmeal] mg [n = 6]) continuously through 28-day treatment cycles. In the first cycle, AA monotherapy was given on days 1–7 for pharmacokinetics, and AA plus prednisone (5 mg twice daily) from days 8 to 28. Of 27 patients, 9 continued treatment with AA until the data cut-off date (18 July 2013). Over the evaluated dose range, plasma abiraterone concentrations increased with dose, with median tmax 2–3 h. At each dose level, mean serum corticosterone concentrations increased, while testosterone and dehydroepiandrosterone sulfate concentrations rapidly decreased following a single AA dose and were further reduced to near the quantification limit on day 8 regardless of the dose. At least 3 patients from each dose-group experienced ≥50% prostate-specific antigen reduction, suggesting clinical benefit from AA in Japanese CRPC patients. AA was generally well-tolerated, and, therefore, the recommended AA dosage regimen in Japanese CRPC patients is 1000 mg oral dose under modified fasting conditions (at least 1 h premeal or 2 h postmeal). This study is registered at ClinicalTrials.gov: NCT01186484. PMID:25117615

  9. Efficacy and safety of modified Yale insulin infusion protocol in Japanese diabetic patients after open-heart surgery.

    PubMed

    Tamaki, Motoyuki; Shimizu, Tomoaki; Kanazawa, Akio; Tamura, Yoshifumi; Hanzawa, Ayame; Ebato, Chie; Itou, Chiharu; Yasunari, Eisuke; Sanke, Haruna; Abe, Hiroko; Kawai, Junko; Okayama, Kaede; Matsumoto, Kazuhisa; Komiya, Koji; Kawaguchi, Minako; Inagaki, Noriko; Watanabe, Takahiro; Kanazawa, Yoshie; Hirose, Takahisa; Kawamori, Ryuzo; Watada, Hirotaka

    2008-09-01

    To our knowledge, there is currently no insulin infusion protocol for critically ill patients especially designed for Asian diabetics although many such protocols are used in Western countries. In this study, we modified the Yale insulin infusion protocol taking into consideration the characteristics of Japanese diabetics and hospital environment. We tested the modified protocol in 40 type 2 diabetic patients after elective open-heart surgery (MY group) comparing with 35 type 2 diabetic patients under empirical blood glucose control (EC group). Analyses of 1656 blood glucose measurements during insulin infusion revealed that percentage of samples that showed achievement of target blood glucose level (80-140 mg/dl) was higher under MY (78+/-15%, n=870) than EC (57+/-23%, n=786, p<0.0001). On the other hand, the percentage of samples in which blood glucose was less than 60 mg/dl was comparable in the two groups (MY: 0.5+/-5.9 per thousand, EC: 5.1+/-18.5 per thousand). None of the patients with hypoglycemia showed significant clinical adverse effects. In conclusion, our modified Yale insulin infusion protocol is effective and safe for tight blood glucose control in Japanese diabetic patients after open-heart surgery.

  10. One-Year Outcomes following Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in Japanese Patients: The APOLLO Study.

    PubMed

    Oshima, Yuji; Kimoto, Kenichi; Yoshida, Noriko; Fujisawa, Kimihiko; Sonoda, Shozo; Kubota, Toshiaki; Murata, Toshinori; Sakamoto, Taiji; Yoshida, Shigeo; Sonoda, Koh-Hei; Ishibashi, Tatsuro

    2017-01-01

    To evaluate 1-year outcomes of intravitreal injections of aflibercept (IVA) in Japanese polypoidal choroidal vasculopathy (PCV) patients. In this prospective, open-label, single-arm multicenter clinical trial, treatment-naïve PCV patients received IVA (2.0 mg) every 2 months, after 3 initial monthly doses. The primary endpoint assessed was the proportion of patients maintaining baseline best-corrected visual acuity (BCVA) at 1 year. Fifty eyes with PCV were included in the study. BCVA was maintained or improved in 97.6% of the patients. Mean logMAR BCVA at baseline was 0.33, and had improved to 0.12 logMAR 1 year after the initiation of aflibercept treatment (p < 0.001). Mean central foveal thickness decreased from 356 to 239 μm (p < 0.001). Complete regression of polypoidal lesions was seen in 72.5% after 1 year of treatment. One year of IVA resulted in stabilization of BCVA and anatomical improvement in Japanese PCV patients. © 2017 S. Karger AG, Basel.

  11. Prevalence of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia in Japanese patients with generalized chronic and aggressive periodontitis.

    PubMed

    Tomita, Sachiyo; Komiya-Ito, Akiyo; Imamura, Kentaro; Kita, Daichi; Ota, Koki; Takayama, Saori; Makino-Oi, Asako; Kinumatsu, Takashi; Ota, Mikio; Saito, Atsushi

    2013-01-01

    This study aimed to investigate the prevalence and levels of major periodontal pathogens, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia in subgingival plaque samples of a group of Japanese patients with aggressive periodontitis (AgP) and chronic periodontitis (CP). A total of 40 patients with clinical diagnosis of AgP or CP and 10 periodontally healthy volunteers were subjected to clinical and microbiological analysis. Subgingival plaque samples were analyzed for A. actinomycetemcomitans, P. gingivalis and T. forsythia with a real-time polymerase chain reaction (PCR) technique. The prevalence of P. gingivalis and T. forsythia was relatively high in patients with periodontitis: over 60% of AgP or CP patients harbored these pathogens whereas they were not detected in the subgingival plaque samples from periodontally healthy individuals. P. gingivalis and T. forsythia were relatively frequently detected together in AgP and CP patients. No significant differences in the prevalence or level of the 3 pathogens were found between periodontitis groups. The proportion of T. forsythia was approximately 4-fold higher in CP group than in AgP group (P = 0.02). In periodontitis patients, a significant positive correlation was found between periodontal parameters (probing depth and clinical attachment level) and the numbers of total bacteria, P. gingivalis and T. forsythia. No distinct pattern of the subgingival profile of these pathogens was discerned between the two disease entities, except for the difference in the proportion of T. forsythia. The red complex bacteria, P. gingivalis and T. forsythia were highly prevalent in this population of Japanese AgP and CP patients, collaborating their roles in periodontitis.

  12. Desmopressin orally disintegrating tablet in Japanese patients with central diabetes insipidus: a retrospective study of switching from intranasal desmopressin.

    PubMed

    Murakami, Takaaki; Hatoko, Tomonobu; Nambu, Takuo; Matsuda, Yuki; Matsuo, Koji; Yonemitsu, Shin; Muro, Seiji; Oki, Shogo

    2014-01-01

    Central diabetes insipidus (CDI) is a rare disease characterized by polyuria and polydipsia. Patients with CDI have been successfully treated with desmopressin administered either by intranasal instillation or oral tablets. Recently, a desmopressin orally disintegrating tablet (ODT) was approved as the first oral desmopressin tablet for CDI treatment in Japan. We conducted a retrospective single-center study of 15 Japanese CDI patients treated with desmopressin ODT therapy, which aimed to evaluate the efficacy and safety of switching to desmopressin ODT and to analyze the clinical factors that affect the desmopressin ODT dose in Japanese patients. The daily mean dose of desmopressin ODT was 104 ± 46.30 μg and the mean ratio of oral to nasal desmopressin dose was 17.0 ± 7.6, both of which are considerably smaller than those of previous dose-titration study. Moreover, the nasal spray group needed significantly smaller ratios of nasal to oral desmopressin than the nasal drop group (11.7 ± 6.5 vs 21.0 ± 5.5, p = 0.02). The ratio of oral to nasal desmopressin dose had a significant inverse correlation with the required nasal desmopressin dose. Multiple regression analysis demonstrated the ratios of nasal to oral desmopressin dose depended on intranasal formulations. In conclusion, desmopressin ODT was safe and effective in the treatment of Japanese adult CDI patients. When switching to ODT, we should care about the possibility that patients require smaller ODT doses than what was initially expected based on previously published data and also nasal formulations in terms of their differences of expected switching ratio.

  13. Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

    PubMed Central

    Kawakami, Takao; Nagasaka, Keiko; Takami, Sachiko; Wada, Kazuya; Tu, Hsiao-Kun; Otsuji, Makiko; Kyono, Yutaka; Dobashi, Tae; Komatsu, Yasuhiko; Kihara, Makoto; Akimoto, Shingo; Peers, Ian S.; South, Marie C.; Higenbottam, Tim; Fukuoka, Masahiro; Nakata, Koichiro; Ohe, Yuichiro; Kudoh, Shoji; Clausen, Ib Groth; Nishimura, Toshihide; Marko-Varga, György; Kato, Harubumi

    2011-01-01

    Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10−25), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control. PMID:21799770

  14. Driving clinical study efficiency by using a productivity breakdown model: comparative evaluation of a global clinical study and a similar Japanese study.

    PubMed

    Takahashi, K; Sengoku, S; Kimura, H

    2011-02-01

    A fundamental management imperative of pharmaceutical companies is to contain surging costs of developing and launching drugs globally. Clinical studies are a research and development (R&D) cost driver. The objective of this study was to develop a productivity breakdown model, or a key performance indicator (KPI) tree, for an entire clinical study and to use it to compare a global clinical study with a similar Japanese study. We, thereby, hope to identify means of improving study productivity. We developed the new clinical study productivity breakdown model, covering operational aspects and cost factors. Elements for improving clinical study productivity were assessed from a management viewpoint by comparing empirical tracking data from a global clinical study with a Japanese study with similar protocols. The following unique and material differences, beyond simple international difference in cost of living, that could affect the efficiency of future clinical trials were identified: (i) more frequent site visits in the Japanese study, (ii) head counts at the Japanese study sites more than double those of the global study and (iii) a shorter enrollment time window of about a third that of the global study at the Japanese study sites. We identified major differences in the performance of the two studies. These findings demonstrate the potential of the KPI tree for improving clinical study productivity. Trade-offs, such as those between reduction in head count at study sites and expansion of the enrollment time window, must be considered carefully. © 2010 Blackwell Publishing Ltd.

  15. Acquired Dyslexia in Three Writing Systems: Study of a Portuguese-Japanese Bilingual Aphasic Patient

    PubMed Central

    Senaha, Mirna Lie Hosogi; de Mattos Pimenta Parente, Maria Alice

    2012-01-01

    The Japanese language is represented by two different codes: syllabic and logographic while Portuguese employs an alphabetic writing system. Studies on bilingual Portuguese-Japanese individuals with acquired dyslexia therefore allow an investigation of the interaction between reading strategies and characteristics of three different writing codes. The aim of this study was to examine the differential impact of an acquired brain lesion on the reading of the logographic, syllabic and alphabetic writing systems of a bilingual Portuguese-Japanese aphasic patient (PF). Results showed impaired reading in the logographic system and when reading irregularly spelled Portuguese words but no effects on reading regular words and nonwords in syllabic and alphabetic writing systems. These dissociations are interpreted according to a multi-route cognitive model of reading assuming selective damage in the lexical route can result in acquired dyslexia across at least three different writing codes. PMID:22713387

  16. Vardenafil allows successful intercourse initiated rapidly after dosing in Japanese patients with diabetes mellitus and erectile dysfunction.

    PubMed

    Nagao, Koichi; Kobayashi, Hideyuki; Fujikawa, Keita; Tachibana, Takashi; Iwamoto, Yasuhiko; Ishii, Nobuhisa; Turek, Paul J; Brant, William O; Kamidono, Sadao

    2009-10-01

    Vardenafil is reported to improve success rates in the maintenance of an erection sufficient for completion of intercourse (SEP-3) compared with placebo in erectile dysfunction (ED) patients who attempted intercourse from as early as 15 minutes after dosing. However, these data were based on general ED patients, using time from administration to initiation of intercourse. It is unclear whether the results can be applied to difficult-to-treat ED patients, such as those with diabetes mellitus (DM), with the time between dosing and insertion into vagina. To determine whether early onset of activity with vardenafil is also achievable in ED patients with DM. Data from a 12-week Phase III clinical trial (randomized, placebo-controlled, double-blind, parallel-group comparison) in Japanese men with ED and DM was used for analysis. In this study, patients received vardenafil 10 mg, 20 mg, or placebo, and were instructed to start sexual activity 1 hour after dosing. Mean per-patient SEP-3 success rates (intent-to-treat; ITT population), based on patient diary question, were calculated by the time between dosing and insertion. The least-squares means and nominal P values for differences versus placebo were derived by analysis of covariance with terms for baseline. SEP-3 success rates in each time interval. The majority of inserts occurred between 60-90 minutes after dosing, but 100 of inserts in 52 patients occurred in the first 30 minutes. SEP-3 success rates in patients who inserted in each interval from 0-15 minutes (P = 0.0268), 15-30 minutes (P = 0.0094) through > 120 minutes were all higher in vardenafil-treated patients than those in placebo. In this retrospective analysis, a rapid onset of activity was also demonstrated in difficult-to-treat ED patients. Vardenafil improved successful intercourse rates compared with placebo in Japanese DM patients who inserted from as early as 15 minutes to >120 minutes after dosing.

  17. Significance of Kampo, Japanese traditional medicine, in the treatment of obesity: basic and clinical evidence.

    PubMed

    Yamakawa, Jun-Ichi; Moriya, Junji; Takeuchi, Kenji; Nakatou, Mio; Motoo, Yoshiharu; Kobayashi, Junji

    2013-01-01

    The cause of obesity includes genetic and environmental factors, including cytokines derived from adipocytes (adipo-cytokines). Although drug therapy is available for obesity, it is highly risky. Our main focus in this review is on the traditional form of Japanese medicine, Kampo, in the treated of obesity. Two Kampo formulas, that is, bofutsushosan () and boiogito (), are covered by the national health insurance in Japan for the treatment of obesity. Various issues related to their action mechanisms remain unsolved. Considering these, we described the results of basic experiments and presented clinical evidence and case reports on osteoarthritis as examples of clinical application of their two Kampo medicine. Traditional medicine is used not only for treatment but also for prevention. In clinical practice, it is of great importance to prove the efficacy of combinations of traditional medicine and Western medicine and the utility of traditional medicine in the attenuation of adverse effects of Western medicine.

  18. Population pharmacokinetic analysis for 10-monohydroxy derivative of oxcarbazepine in pediatric epileptic patients shows no difference between Japanese and other ethnicities.

    PubMed

    Sugiyama, Ikuo; Bouillon, Thomas; Yamaguchi, Masayuki; Suzuki, Hikoe; Hirota, Takashi; Fink, Martin

    2015-04-01

    Oxcarbazepine is an anti-epileptic drug, which is almost completely metabolized by cytosolic enzymes in the liver to the active 10-monohyroxy metabolite (MHD) following oral administration. The pharmacokinetic (PK) profiles of MHD were evaluated in pediatric epileptic patients and a possible ethnic difference in PK of MHD between Japanese and non-Japanese pediatric patients was assessed. A non-linear mixed effect modeling approach was used to determine the PK of MHD. A one-compartment population model with first-order absorption appropriately described the PK of MHD. No clinically relevant differences were found for using body surface area or weight to explain between-patient variability, therefore the final model included the effects of body weight on apparent clearance (CL/F) and apparent volume of distribution (V/F) of MHD, and in addition, the effect of 3 concomitant anti-epileptic drugs (carbamazepine, phenobarbital and phenytoin) on CL/F of MHD. Inclusion of ethnicity as a covariate in the final model, concluded no ethnic difference with respect to CL/F of MHD between Japanese and non-Japanese patients. Hence, oxcarbazepine can be generally applied using the same dosage and administration for the treatment of partial onset seizures in pediatric patients, regardless of ethnicity.

  19. Efficacy and Safety of Bitopertin in Patients with Schizophrenia and Predominant Negative Symptoms: Subgroup Analysis of Japanese Patients from the Global Randomized Phase 2 Trial

    PubMed Central

    Sato, Shin-Ichi; Shuto, Norifumi; Nakano, Miwa; Higuchi, Teruhiko

    2017-01-01

    Objective The aim of the present study was to perform a subgroup analysis of data from a phase II global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of bitopertin, a glycine reuptake inhibitor that activates N-methyl-D-aspartate receptors by increasing the concentration of glycine in the synaptic cleft, in Japanese and non-Japanese patients with schizophrenia and predominant negative symptoms. Methods Patients with schizophrenia and predominant negative symptoms on one or two antipsychotic drugs, including atypical antipsychotic drugs (olanzapine, risperidone, quetiapine, aripiprazole, and paliperidone) as the primary treatment, received bitopertin (10, 30, or 60 mg/day) or placebo once daily for 8 weeks as an add-on treatment. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) negative symptom factor score (NSFS). Results The efficacy of bitopertin (10 mg and 30 mg) was similar between Japanese and non-Japanese patients. In the bitopertin 60-mg group, no difference from the placebo group was observed in Japanese or non-Japanese patients. The response to placebo was lower in Japanese patients, and there was a trend towards a greater difference in the change in PANSS NSFS between the placebo group and the 10-mg and 30-mg groups among Japanese patients. The safety profile of bitopertin was favorable in Japanese and non-Japanese patients. Conclusion According to this subgroup analysis from a global phase II study of bitopertin, there was no difference in terms of efficacy and safety between Japanese and non-Japanese patients. PMID:28096877

  20. Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients.

    PubMed

    Atsuta, Naoki; Watanabe, Hirohisa; Ito, Mizuki; Banno, Haruhiko; Suzuki, Keisuke; Katsuno, Masahisa; Tanaka, Fumiaki; Tamakoshi, Akiko; Sobue, Gen

    2006-06-01

    Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motoneuron disease caused by a CAG-repeat expansion in the androgen receptor (AR) gene and for which no curative therapy exists. However, since recent research may provide opportunities for medical treatment, information concerning the natural history of SBMA would be beneficial in planning future clinical trials. We investigated the natural course of SBMA as assessed by nine activities of daily living (ADL) milestones in 223 Japanese SBMA patients (mean age at data collection = 55.2 years; range = 30-87 years) followed from 1 to 20 years. All the patients were diagnosed by genetic analysis. Hand tremor was an early event that was noticed at a median age of 33 years. Muscular weakness occurred predominantly in the lower limbs, and was noticed at a median age of 44 years, followed by the requirement of a handrail to ascend stairs at 49, dysarthria at 50, dysphagia at 54, use of a cane at 59 and a wheelchair at 61 years. Twenty-one of the patients developed pneumonia at a median age of 62 and 15 of them died at a median age of 65 years. The most common cause of death in these cases was pneumonia and respiratory failure. The ages at onset of each ADL milestone were strongly correlated with the length of CAG repeats in the AR gene. However CAG-repeat length did not correlate with the time intervals between each ADL milestone, suggesting that although the onset age of each ADL milestone depends on the CAG-repeat length in the AR gene, the rate of disease progression does not. The levels of serum testosterone, an important triggering factor for polyglutamine-mediated motoneuron degeneration, were maintained at relatively high levels even at advanced ages. These results provide beneficial information for future clinical therapeutic trials, although further detailed prospective studies are also needed.

  1. High serum parathyroid hormone and calcium are risk factors for hypertension in Japanese patients.

    PubMed

    Yagi, Shusuke; Aihara, Ken-ichi; Kondo, Takeshi; Endo, Itsuro; Hotchi, Junko; Ise, Takayuki; Iwase, Takashi; Akaike, Masashi; Matsumoto, Toshio; Sata, Masataka

    2014-01-01

    Excess parathyroid hormone (PTH), known as primary hyperparathyroidism (pHPT), results in hypercalcemia and bone loss. Recent studies have shown that PTH is associated with the occurrence of hypertension in Western countries; however, controversy remains regarding high serum levels of PTH and calcium as risk factors for hypertension in Japanese patients. We retrospectively enrolled 114 consecutive Japanese patients who visited our hospital for examination and treatment of hypercalcemia and/or hypertension with serum calcium levels ≥ 9.8 mg/dL. To estimate the prevalence of hypertension, the patients were categorized according to calcium levels into hypercalcemic (10.2-13.4 mg/dL) and normocalcemic (9.8-10.1 mg/dL) groups, which were further categorized into high PTH (50-440 pg/mL) and low PTH (8-49 pg/mL) groups. The prevalence of hypertension was higher in patients with hypercalcemia than in patients with normocalcemia in both the high and low PTH groups. The prevalence of hypertension was higher in patients with high serum PTH levels than in patients with low serum PTH levels in both the hypercalcemic and normocalcemic groups. Logistic multiple regression analysis determined that serum calcium (P < 0.05) and PTH (P < 0.01) levels were positive contributors to hypertension. In conclusion, high serum levels of PTH and calcium are risk factors for hypertension in Japanese patients.

  2. Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection

    PubMed Central

    Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

    2015-01-01

    AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. METHODS: A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. RESULTS: Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal

  3. Safety, efficacy and pharmacokinetics of humanized anti-CD52 monoclonal antibody alemtuzumab in Japanese patients with relapsed or refractory B-cell chronic lymphocytic leukemia.

    PubMed

    Ishizawa, Kenichi; Fukuhara, Noriko; Nakaseko, Chiaki; Chiba, Shigeru; Ogura, Michinori; Okamoto, Akihiko; Sunaga, Yoshinori; Tobinai, Kensei

    2017-01-01

    To evaluate the safety, efficacy and pharmacokinetics of alemtuzumab in Japanese patients, we conducted a phase I study in patients with relapsed or refractory B-cell chronic lymphocytic leukemia. Six patients received alemtuzumab by intravenous infusion every other day three times a week for 12 weeks. The dose was gradually escalated on daily basis (3, 10 and then 30 mg) until the patient tolerated. The primary objective was to evaluate the safety of alemtuzumab in Japanese patients and the secondary objectives were to evaluate the overall response rate and the pharmacokinetics. The major treatment-emergent adverse events were anemia, neutropenia (6/6 patients each) and thrombocytopenia (5/6 patients) in hematologic adverse events, and nausea, vomiting, decreased appetite, cytomegalovirus test positive and pyrexia (4/6 patients) in non-hematologic adverse events. As serious adverse events, cytomegalovirus infection, pulmonary tuberculosis and diffuse large B-cell lymphoma were reported in 1/6 patient each. The overall response rate was 33% (95% confidence interval: 4-78) (1/6 patient each achieved complete response and partial response, respectively) and 3/6 patients had stable disease and 1/6 patient had progressive disease. The median time to response was 2.9 months. After last intravenous dosing (Week 12) of alemtuzumab 30 mg every other day three times a week, Cmax, tmax, AUC0-τ and t1/2 were higher and CL and Vss were lower than the values observed after the first dose. The efficacy, safety and pharmacokinetics results observed with alemtuzumab in Japanese patients were generally similar to those reported in overseas clinical studies. Alemtuzumab at 30 mg by intravenous infusion every other day three times a week for 12 weeks should be safe and effective similarly in Japanese B-cell chronic lymphocytic leukemia patients. NCT00923182. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Pharmacokinetics, Pharmacodynamics, and Safety of Canagliflozin in Japanese Patients with Type 2 Diabetes Mellitus.

    PubMed

    Iijima, Hiroaki; Kifuji, Takayuki; Maruyama, Nobuko; Inagaki, Nobuya

    2015-08-01

    Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved worldwide for the treatment of patients with type 2 diabetes mellitus (T2DM). The present study evaluated pharmacokinetics, pharmacodynamics, and safety of canagliflozin in Japanese patients with T2DM. Canagliflozin, at doses of 25, 100, 200, or 400 mg, was administered as a single dose and, after a washout of 1 day, in repeated doses for 14 consecutive days to 61 subjects in a randomized, double-blind, placebo-controlled study. Plasma concentrations of canagliflozin and urinary glucose excretion (UGE) were measured, and renal threshold for glucose excretion (RTG) was calculated. Safety was evaluated on the basis of adverse event (AE) reports, blood and urine laboratory parameters, and vital signs. Plasma canagliflozin maximum concentration and area under the concentration-time curve (AUC) values increased in a dose-dependent manner with the time to maximum concentration (t max) of 1.0 h and elimination half-life (t 1/2) of 10.22-13.26 h on Day 1. No significant changes in t max and t 1/2 were observed after multiple-dose administration. The linearity factors, as calculated from the ratios of AUC0-24h on Day 16 to AUC0-∞ on Day 1, were close to 1 in all canagliflozin groups. Canagliflozin increased UGE0-24h (80-110 g/day with canagliflozin ≥100 mg) and decreased RTG from the first day of treatment; these effects were sustained during the entire period of multiple administration. No significant AEs were noted. Urine volume was slightly increased on Day 1, but subsequent changes after repeated doses for 14 days were small. Urinary sodium tended to be higher in the early treatment period, whereas no particular change was observed in serum osmolality and hematocrit. Canagliflozin increased UGE, decreased RTG, and was well tolerated throughout the entire period of multiple administrations in Japanese patients with T2DM. Mitsubishi Tanabe Pharma Corporation. ClinicalTrials.gov#NCT00707954.

  5. BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer.

    PubMed

    Sakamoto, Ikuko; Hirotsu, Yosuke; Nakagomi, Hiroshi; Ouchi, Hidetaka; Ikegami, Atsushi; Teramoto, Katsuhiro; Amemiya, Kenji; Mochizuki, Hitoshi; Omata, Masao

    2016-01-01

    The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer. Ninety-five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next-generation sequencing. Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high-grade serous adenocarcinomas). In this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers. © 2015 American Cancer Society.

  6. Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose–response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial

    PubMed Central

    Takeuchi, Tsutomu; Tanaka, Yoshiya; Ishiguro, Naoki; Yamanaka, Hisashi; Yoneda, Toshiyuki; Ohira, Takeshi; Okubo, Naoki; Genant, Harry K

    2016-01-01

    Objectives To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). Methods In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. Results Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. Conclusions Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. Trial registration number JapicCTI-101263. PMID:26585988

  7. Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial.

    PubMed

    Takeuchi, Tsutomu; Tanaka, Yoshiya; Ishiguro, Naoki; Yamanaka, Hisashi; Yoneda, Toshiyuki; Ohira, Takeshi; Okubo, Naoki; Genant, Harry K; van der Heijde, Désirée

    2016-06-01

    To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. JapicCTI-101263. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Eye movement during facial affect recognition by patients with schizophrenia, using Japanese pictures of facial affect.

    PubMed

    Shiraishi, Yuko; Ando, Kazuhiro; Toyama, Sayaka; Norikane, Kazuya; Kurayama, Shigeki; Abe, Hiroshi; Ishida, Yasushi

    2011-10-01

    A possible relationship between recognition of facial affect and aberrant eye movement was examined in patients with schizophrenia. A Japanese version of standard pictures of facial affect was prepared. These pictures of basic emotions (surprise, anger, happiness, disgust, fear, sadness) were shown to 19 schizophrenic patients and 20 healthy controls who identified emotions while their eye movements were measured. The proportion of correct identifications of 'disgust' was significantly lower for schizophrenic patients, their eye fixation time was significantly longer for all pictures of facial affect, and their eye movement speed was slower for some facial affects (surprise, fear, and sadness). One index, eye fixation time for "happiness," showed a significant difference between the high- and low-dosage antipsychotic drug groups. Some expected facial affect recognition disorder was seen in schizophrenic patients responding to the Japanese version of affect pictures, but there was no correlation between facial affect recognition disorder and aberrant eye movement.

  9. Combined Clozapine and Electroconvulsive Therapy in a Japanese Schizophrenia Patient: A Case Report

    PubMed Central

    Ozaki, Yuki; Kawasoe, Koichiro; Ochi, Shinichiro; Niiya, Takanori; Sonobe, Naomi; Matsumoto, Teruhisa; Ueno, Shu-ichi

    2014-01-01

    Clozapine is well-known for successful use in schizophrenic patients treatment resistant to other antipsychotics. However, even with clozapine, 25% of schizophrenic patients are not in remission. Recently, as adjunctive treatment with clozapine, electroconvulsive therapy has been reported to be an effective and safe adjunctive treatment. We report a Japanese schizophrenic woman who was not in remission with clozapine alone but with both clozapine and electroconvulsive therapy. PMID:25191508

  10. Reliability, validity, and responsiveness of the Japanese version of International Restless Legs Syndrome Study Group rating scale for restless legs syndrome in a clinical trial setting.

    PubMed

    Inoue, Yuichi; Oka, Yasunori; Kagimura, Tatsuo; Kuroda, Kenji; Hirata, Koichi

    2013-09-01

    This study was conducted to verify the reliability, validity, and responsiveness of the Japanese version of the International Restless Legs Syndrome Study Group Rating Scale for restless legs syndrome (J-IRLS) as a sub-study of a clinical trial of pramipexole against restless legs syndrome. After evaluating the test-retest reliability, concurrent validity and construct validity were analyzed. The responsiveness of J-IRLS was confirmed by evaluating the correlations between the changes in J-IRLS total score after treatment, Clinical Global Impression Improvement Scale (CGI-I), and Patient Global Impression. Test-retest reliability of J-IRLS was good (intra-class correlation coefficient, 0.877; 95% confidence interval, 0.802-0.925). The correlation coefficient of J-IRLS total score and CGI-S score for the first and second visit was 0.804 and 0.796, respectively (both P < 0.0001). Factor analysis of J-IRLS itemsalone identified a two-factor structure. Exploratory analysis on 10 items of J-IRLS together with the Japanese version of the Pittsburgh Sleep Quality Index revealed that several items on the Japanese version of the Pittsburgh Sleep Quality Index appeared as the third factor. The correlations of CGI-I and Patient Global Impression with change in J-IRLS total score after treatment were highly significant. Reliability, validity, and responsiveness of J-IRLS were considered adequate. The scale is highly applicable both for evaluating the severity of restless legs syndrome and for assessing drug efficacy. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

  11. Efficacy and safety of single fecal microbiota transplantation for Japanese patients with mild to moderately active ulcerative colitis.

    PubMed

    Nishida, Atsushi; Imaeda, Hirotsugu; Ohno, Masashi; Inatomi, Osamu; Bamba, Shigeki; Sugimoto, Mitsushige; Andoh, Akira

    2017-04-01

    The clinical utility of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC) is still controversial. We investigated the efficacy and safety of single FMT for patients with mild to moderately active UC in a Japanese population. Fifty-seven patients were evaluated for eligibility, and 16 patients were excluded. Forty-one patients with UC refractory to standard medical therapy were treated with single FMT by colonoscopic administration. Changes in the fecal microbiota were assessed by 16S ribosomal DNA based terminal restriction fragment length polymorphism analysis. At 8 weeks after FMT, no patient achieved clinical remission, and 11 of 41 patients (26.8 %) showed clinical response. The full Mayo score and the Mayo clinical score significantly decreased at week 8 [full Mayo score 5.5 ± 2.4 (mean ± standard deviation) at initiation and 4.6 ± 2.2 at week 8, P < 0.004; Mayo clinical score 4.0 ± 2.0 at initiation and 3.0 ± 1.9 at week 8, P < 0.001], but there were no statistically significant effects on the Mayo endoscopic score. No adverse events occurred after FMT or during the follow-up period of 8 weeks. The proportion of Bifidobacterium was significantly higher in the donor feces used for responders than in the donor feces used for nonresponders. The proportion of Lactobacillales and Clostridium cluster IV were significantly higher in the donor feces used for nonresponders. Single FMT by colonoscopy was performed safely in all patients, but sufficient clinical efficacy and microbial restoration were not confirmed in patients with mild to moderately active UC.

  12. Impact of clinic follow-up visits on body weight control in people with prediabetes or diabetes mellitus: Japanese nonelderly cohort study.

    PubMed

    Ono, Sachiko; Ono, Yosuke; Matsui, Hiroki; Yasunaga, Hideo

    2017-09-01

    Body weight control is considered essential for the management of diabetes mellitus. Clinicians have an important role in educating and guiding patients with diabetes to control their body weight. The aim of the present study was to clarify if clinic visits influenced body weight control of people with prediabetes or diabetes mellitus. To examine whether individuals with diabetes mellitus who visit clinics show better weight control. We used a large Japanese database (Japan Medical Data Center, Tokyo, Japan) of screening for lifestyle disease linked with administrative claim data to retrospectively identify people with prediabetes or diabetes mellitus based on their fasting plasma glucose and glycated haemoglobin (HbA1c) concentration. We collected data on their baseline characteristics (including age, sex, body mass index and disease history) and their lifestyles. We used propensity-score inverse probability of treatment weighted generalized estimating equations to examine the association between clinic visits and change in body mass index. Between 2013 and 2014, we identified 11004 individuals with prediabetes or diabetes. The proportions visiting clinics after the first diagnosis made at screening was 27.8%. Clinic visit was significantly associated with lower body mass index after adjustment for baseline patient characteristics a year after first screening (-0.17 kg/m2; 95% confidence interval, -0.22 to -0.12). In Japanese people found to have prediabetes or diabetes during an annual health screen, those who visited clinics after their first diagnosis were likely to have better body weight control.

  13. Views of Japanese patients on the advantages and disadvantages of hemodialysis and peritoneal dialysis.

    PubMed

    Nakamura-Taira, Nanako; Muranaka, Yoshimi; Miwa, Masako; Kin, Seikon; Hirai, Kei

    2013-08-01

    The preference for dialysis modalities is not well understood in Japan. This study explored the subjective views of Japanese patients undergoing dialysis regarding their treatments. The participants were receiving in-center hemodialysis (CHD) or continuous ambulatory peritoneal dialysis (CAPD). In Study 1, 34 participants (17 CHD and 17 CAPD) were interviewed about the advantages and disadvantages of dialysis modalities. In Study 2, 454 dialysis patients (437 CHD and 17 CAPD) rated the advantages and disadvantages of CHD and CAPD in a cross-sectional survey. Interviews showed that professional care and dialysis-free days were considered as advantages of CHD, while independence, less hospital visits, and flexibility were considered as advantages of CAPD. Disadvantages of CHD included restriction of food and fluids and unpleasant symptoms after each dialysis session. Catheter care was an additional disadvantage of CAPD. Survey showed that the highly ranked advantages were professional care in CHD and less frequent hospital visits in CAPD, while the highly ranked disadvantages were concerns about emergency and time restrictions in CHD, and catheter care and difficulty in soaking in a bath in CAPD. The total scores of advantages and disadvantages showed that CHD patients subjectively rated their own modality better CHD over CAPD, while CAPD patients had the opposite opinion. The results of this study indicate that the factors affecting the decision-making process of Japanese patients are unique to Japanese culture, namely considering the trouble caused to the people around patients (e.g., families, spouses, and/or caregivers).

  14. Study abroad experience is related to Japanese doctors' behavior to see foreign patients.

    PubMed

    Tamamaki, Kinko; Nishio, Hisahide

    2013-04-17

    Globalization in Japan involves increases in the number of foreign residents. While there are some English-speaking Japanese doctors that are willing to see foreign patients, many are reluctant to do so. In this study, we attempted to clarify the factors that encourage Japanese doctors to see foreign patients. We conducted a questionnaire survey among medical doctors in Kobe City, Japan. The questionnaire was distributed to 172 doctors, and we received 139 responses. Statistical analysis showed a significant correlation between the frequency of seeing foreign patients and having the experience of studying abroad (p<0.05), confirming our hypothesis. There was also a significant correlation between having the experience of studying abroad and the doctors' self-evaluations of their English ability (p<0.05). There was no significant correlation found, however, between the frequency of seeing foreign patients and that of reading English research articles. These data suggested that the experience of living abroad rather than the exposure to English research articles was more highly correlated with seeing greater numbers of foreign patients. In conclusion, greater exposure to colloquial English was one of the determinants of the doctors' greater willingness to see foreign patients. In the Japanese medical education curriculum, therefore, it would be necessary to offer alternatives to studying abroad for those students who do not have such opportunities.

  15. Daytime sleepiness in Japanese patients with multiple system atrophy: prevalence and determinants

    PubMed Central

    2012-01-01

    Background The recent SLEEMSA study that evaluated excessive daytime sleepiness (EDS) in Caucasian patients with multiple system atrophy (MSA) demonstrated that EDS was more frequent in patients (28%) than in healthy subjects (2%). However, the prevalence and determinants of EDS in other ethnic populations have not been reported to date. Methods We performed a single-hospital prospective study on patients with probable MSA. To ascertain the prevalence and determinants of EDS in Japanese MSA patients, we assessed the patients’ degree of daytime sleepiness by using the Japanese version of the Epworth Sleepiness Scale (ESS). In addition, we investigated the effects of sleep-disordered breathing (SDB) and abnormal periodic leg movements in sleep (PLMS), which were measured by polysomnography, on the patients’ ESS scores. Results A total of 25 patients with probable MSA (21 patients with cerebellar MSA and 4 patients with parkinsonian MSA) were included in this study. All patients underwent standard polysomnography. The mean ESS score was 6.2 ± 0.9, and EDS was identified in 24% of the patients. SDB and abnormal PLMS were identified in 24 (96%) and 11 (44%) patients, respectively. The prevalences of EDS in patients with SDB and abnormal PLMS were 25% and 18%, respectively. No correlations were observed between ESS scores and the parameters of SDB or abnormal PLMS. Conclusions The frequency of EDS in Japanese patients with MSA was similar to that in Caucasian MSA patients. SDB and abnormal PLMS were frequently observed in MSA patients, although the severities of these factors were not correlated with EDS. Further investigations using objective sleep tests need to be performed. PMID:23116490

  16. Xeroderma pigmentosum complementation group F: Report of a case and review of Japanese patients.

    PubMed

    Tofuku, Yukari; Nobeyama, Yoshimasa; Kamide, Ryoichi; Moriwaki, Shinichi; Nakagawa, Hidemi

    2015-09-01

    Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by extraordinary sensitivity to sunlight, resulting in cutaneous malignant tumors. Among XP, XP-F presents relatively uniquely in Japanese. To clarify the characteristics of this group, we describe a case of XP-F and review Japanese cases previously reported. A 50-year-old Japanese woman was referred to us with multiple, variously sized, light- or dark-brown macules on the face and sunlight-exposed extremities. She had experienced bulla formation with approximately 10 min of sunlight exposure during her elementary school years. Her parents had been first cousins, and her mother and sister had photosensitivity. She showed no neurological or developmental abnormalities. Ultraviolet (UV) irradiation testing revealed normal levels for minimal erythema dose with UV-A and UV-B. Sensitivity to UV-C and DNA repair ability in the patient's fibroblasts were indicated between that in normal individuals and that in an XP-A patient. Complementation assay revealed that transfection of the XPF gene led most efficient DNA repair compared with the other XP genes. Therefore, the patient was diagnosed with XP-F. Twenty-three cases of Japanese patients (six males, 17 females) with XP-F have been reported, including the present case. Our review suggested a relatively high prevalence of 50% (11/22) for cutaneous malignant tumors. A significant difference was evident in the mean age at first medical consultation between patients with cutaneous malignant tumors (53.6 years) and patients without such tumors (30.8 years). This suggests that cutaneous malignant tumors could occur in the age range of 30-50 years in XP-F patients.

  17. Relationships between serum irisin levels and metabolic parameters in Japanese patients with obesity.

    PubMed

    Fukushima, Yaeko; Kurose, Satoshi; Shinno, Hiromi; Cao Thi Thu, Ha; Tamanoi, Atsuko; Tsutsumi, Hiromi; Hasegawa, Takaaki; Nakajima, Toshiaki; Kimura, Yutaka

    2016-06-01

    Irisin is a skeletal muscle myokine that causes the brown coloration of white fat, promotes fat burning, inhibits weight gain and may be useful for treatment of obesity. Irisin is also related to glucose/lipid metabolism and may prevent onset of diabetes, but a consensus on irisin secretion has not been reached. The purpose of this study was to determine the relationships between serum irisin levels and physical factors in untreated Japanese men and women with obesity. The subjects were 66 untreated patients with obesity (body mass index ≥30 kg m(-2)) who visited our obesity clinic. The subjects included 19 men and 47 women with a mean age of 45.7 ± 13.4 years, mean body weight of 93.8 ± 17.6 kg, and mean body mass index of 36.5 ± 4.7 kg m(-2). At the initial visit, blood sampling was performed, body composition was evaluated using dual energy X-ray absorptiometry, and exercise tolerance was determined in a cardiopulmonary exercise test. Homeostasis model of assessment - insulin resistance (HOMA-IR), an index of insulin resistance, and the serum level of irisin were measured. In men, serum irisin was positively correlated with fasting blood glucose (r = 0.491, P < 0.05), immunoreactive insulin (r = 0.536, P < 0.05), HOMA-IR (r = 0.635, P < 0.01), body weight (r = 0.491, P < 0.05), lean body mass of the trunk (r = 0.579, P < 0.05) and whole lean body mass (r = 0.489, P < 0.05). In women, serum irisin was positively correlated with immunoreactive insulin (r = 0.502, P < 0.01) and HOMA-IR (r = 0.385, P < 0.01). In both sexes, HOMA-IR was an independent variable associated with obesity (men: β = 0.635, R(2) = 0.369, P < 0.01; women: β = 0.385, R(2) = 0.129, P < 0.01). The serum level of irisin was positively correlated with HOMA-IR in Japanese patients with obesity of both sexes. This suggests that compensatory enhancement of irisin secretion may

  18. First reports of esophageal adenocarcinoma with white globe appearance in Japanese and Caucasian patients

    PubMed Central

    Tonai, Yusuke; Ishihara, Ryu; Yamasaki, Yasushi; Kanesaka, Takashi; Yamamoto, Sachiko; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Uedo, Noriya; Tomita, Yasuhiko; Iishi, Hiroyasu

    2016-01-01

    Background and study aims: Better endoscopic diagnosis in case of Barrett’s esophagus is still needed. White globe appearance (WGA) is a novel endoscopic marker for gastric adenocarcinoma, with high sensitivity for differentiating between gastric cancer/high-grade dysplasia and other lesions. We report 2 cases of esophageal adenocarcinoma with WGA. In Case 1, esophagogastroduodenoscopy (EGD) revealed a 10-mm esophageal adenocarcinoma in a 48-year-old Japanese woman with short-segment Barrett’s esophagus. A small (< 1 mm) white globular lesion, typical of WGA, was observed under the epithelium by magnifying narrow-band imaging. A dilated neoplastic gland with eosinophilic material and necrotic epithelial fragments was identified at the site of the WGA by histologic examination. In Case 2, EGD revealed a 5-mm esophageal adenocarcinoma in a 60-year-old Caucasian man with long-segment Barrett’s esophagus. A typical WGA was observed by magnifying narrow-band imaging and similar histologic findings were identified at the site of the WGA. WGA could be a reliable endoscopic finding for target biopsy in esophageal adenocarcinoma, if its specificity is as high as in gastric cancer. The clinical implications of WGA in patients with Barrett’s esophagus should be investigated further. PMID:27747281

  19. Qualitative Analysis of the Resilience of Adult Japanese Patients with Type 1 Diabetes.

    PubMed

    Nishio, Ikuko; Chujo, Masami

    2016-09-01

    Resilience strategies are what we use to avoid and recover from error. In this study, we used the grounded theory approach to evaluate the resilience of Japanese patients with Type 1 diabetes. Semi-structured interviews were conducted with 15 adults with Type 1 diabetes. Then, using grounded theory, we created a new model of resilience in this population. The results suggested a core category, "to make progress along the resilience path," comprising seven concepts classified into three stages. These seven concepts were as follows: "suffering from treatment," "damaged trust as a person," "persistence of afflictions," "awareness of supporters," "joy to be kept alive by insulin," "actively seeking a future," "being able to manage by oneself." Individuals with Type 1 diabetes used difficult experiences to motivate their resilience and to improve their situation. Additionally, resilience was an important contributor to these individuals' beliefs in their ability to face difficulties, to accept their illness and insulin therapy, and to control their illness. Resilience was also important to these individuals' faith in the future and in medical care. Our results are applicable to clinical care and research, such as the development of preventive interventions aimed at building or strengthening protective skills related to diabetes and its management. Ultimately, our goal is to equip adults with Type 1 diabetes with the tools to obtain sufficient behavioral and health-related resilience. Furthermore, these results highlight that maintaining resilience-related coping skills is important for adults and indicate that different psychological processes underlie resilience across the lifespan.

  20. Higher Prevalence of Epstein–Barr Virus DNA in Deeper Periodontal Pockets of Chronic Periodontitis in Japanese Patients

    PubMed Central

    Kato, Ayako; Imai, Kenichi; Ochiai, Kuniyasu; Ogata, Yorimasa

    2013-01-01

    Periodontitis, a complex chronic inflammatory disease caused by subgingival infection, is among the most prevalent microbial diseases in humans. Although traditional microbiological research on periodontitis has focused on putative bacteria such as Porphyromonas gingivalis, the herpes virus is proposed to be involved in the pathogenesis of periodontitis because bacterial etiology alone does not adequately explain various clinical aspects. In this study, we established for the first time, more Epstein–Barr virus (EBV) DNA is found deeper in periodontal pockets of chronic periodontitis in Japanese patients. Subgingival samples were collected from 85 patients with chronic periodontitis having two periodontal sites with probing depths (PD) of ≤3 mm (shallow) or ≥5 mm (deep) and were subjected to a nested polymerase chain reaction. EBV DNA was more frequently detected in patients with deeper PD sites (66%) than in those with shallow PD sites (48%) or healthy controls (45%). Coexistence of EBV DNA and P. gingivalis was significantly higher in patients with deeper PD sites (40%) than in those with shallow PD sites (14%) or healthy controls (13%). Although no difference in clinical index for periodontitis, the odds ratio of EBV DNA in patients with deeper PD sites was 2.36, which was 2.07-fold higher than that in those with shallow PD sites. Interestingly, the odds of acquiring chronic periodontitis (PD ≥5 mm) were higher in the presence of both EBV DNA and P. gingivalis compared with either EBV DNA or P. gingivalis only. In addition, we also observed that EBV-encoded small RNA (EBER) in positive cells of human gingival tissues. These results would suggest that EBV DNA may serve as a pathogenic factor leading to chronic periodontitis among Japanese patients. PMID:23991022

  1. Outcomes of single- or dual-chamber implantable cardioverter defibrillator systems in Japanese patients

    PubMed Central

    Ueda, Akiko; Oginosawa, Yasushi; Soejima, Kyoko; Abe, Haruhiko; Kohno, Ritsuko; Ohe, Hisaharu; Momose, Yuichi; Nagaoka, Mika; Matsushita, Noriko; Hoshida, Kyoko; Miwa, Yosuke; Miyakoshi, Mutsumi; Togashi, Ikuko; Maeda, Akiko; Sato, Toshiaki; Yoshino, Hideaki

    2015-01-01

    Background There are no criteria for selecting single- or dual-chamber implantable cardioverter defibrillators (ICDs) in patients without a pacing indication. Recent reports showed no benefit of the dual-chamber system despite its preference in the United States. As data on ICD selection and respective outcomes in Japanese patients are scarce, we investigated trends regarding single- and dual-chamber ICD usage in Japan. Methods Data from a total of 205 ICD recipients with structural heart disease (median age, 63 years) in two Japanese university hospitals were reviewed. Patients with bradycardia with a pacing indication and permanent atrial fibrillation at implantation were excluded. Results Single- and dual-chamber ICDs were implanted in 36 (18%) and 169 (82%) patients, respectively. Non-ischemic cardiomyopathy dominated both groups. Seventeen dual-chamber patients developed atrial pacing-dependency over 4.5 years, and it developed immediately after implantation in 14. Although preoperative testing showed no sign of bradycardia in these patients, their pacing rate was set higher than it was in patients who were pacing-independent (61 vs. 46 paces per min, p<0.01). Two single-chamber patients (5%) underwent atrial lead insertion. While inappropriate shock equally occurred in both groups (7 vs. 21 patients, single- vs. dual-chamber, P=0.285), device-related infection occurred only in dual-chamber patients (0 vs. 9 patients, P=0.155). No differences in death or heart failure hospitalization were observed between groups. Conclusions Dual-chamber ICDs were four-fold more common in Japanese patients without a pacing indication. No benefit over single-chamber ICD was observed. Newly developed atrial pacing-dependency seemed to be limited and could have been overestimated due to higher pacing rate settings in dual-chamber patients. PMID:27092188

  2. Structural equation modeling of factors contributing to quality of life in Japanese patients with multiple sclerosis.

    PubMed

    Kikuchi, Hiromi; Mifune, Nobuhiro; Niino, Masaaki; Kira, Jun-Ichi; Kohriyama, Tatsuo; Ota, Kohei; Tanaka, Masami; Ochi, Hirofumi; Nakane, Shunya; Kikuchi, Seiji

    2013-01-22

    To improve quality of life (QOL) in patients with multiple sclerosis (MS), it is important to decrease disability and prevent relapse. The aim of this study was to examine the causal and mutual relationships contributing to QOL in Japanese patients with MS, develop path diagrams, and explore interventions with the potential to improve patient QOL. Data of 163 Japanese MS patients were obtained using the Functional Assessment of MS (FAMS) and Nottingham Adjustment Scale-Japanese version (NAS-J) tests, as well as four additional factors that affect QOL (employment status, change of income, availability of disease information, and communication with medical staff). Data were then used in structural equation modeling to develop path diagrams for factors contributing to QOL. The Expanded Disability Status Scale (EDSS) score had a significant effect on the total FAMS score. Although EDSS negatively affected the FAMS symptom score, NAS-J subscale scores of anxiety/depression and acceptance were positively related to the FAMS symptom score. Changes in employment status after MS onset negatively affected all NAS-J scores. Knowledge of disease information improved the total NAS-J score, which in turn improved many FAMS subscale scores. Communication with doctors and nurses directly and positively affected some FAMS subscale scores. Disability and change in employment status decrease patient QOL. However, the present findings suggest that other factors, such as acquiring information on MS and communicating with medical staff, can compensate for the worsening of QOL.

  3. Structural equation modeling of factors contributing to quality of life in Japanese patients with multiple sclerosis

    PubMed Central

    2013-01-01

    Background To improve quality of life (QOL) in patients with multiple sclerosis (MS), it is important to decrease disability and prevent relapse. The aim of this study was to examine the causal and mutual relationships contributing to QOL in Japanese patients with MS, develop path diagrams, and explore interventions with the potential to improve patient QOL. Methods Data of 163 Japanese MS patients were obtained using the Functional Assessment of MS (FAMS) and Nottingham Adjustment Scale-Japanese version (NAS-J) tests, as well as four additional factors that affect QOL (employment status, change of income, availability of disease information, and communication with medical staff). Data were then used in structural equation modeling to develop path diagrams for factors contributing to QOL. Results The Expanded Disability Status Scale (EDSS) score had a significant effect on the total FAMS score. Although EDSS negatively affected the FAMS symptom score, NAS-J subscale scores of anxiety/depression and acceptance were positively related to the FAMS symptom score. Changes in employment status after MS onset negatively affected all NAS-J scores. Knowledge of disease information improved the total NAS-J score, which in turn improved many FAMS subscale scores. Communication with doctors and nurses directly and positively affected some FAMS subscale scores. Conclusions Disability and change in employment status decrease patient QOL. However, the present findings suggest that other factors, such as acquiring information on MS and communicating with medical staff, can compensate for the worsening of QOL. PMID:23339479

  4. Time-Dependent Changes in Psychosocial Distress in Japanese Patients with Implantable Cardioverter Defibrillators.

    PubMed

    Saito, Nao; Taru, Chiemi; Miyawaki, Ikuko

    2016-12-02

    This prospective study clarified changes in the mood states of Japanese patients with implantable cardioverter defibrillators as well as factors related to the mood states. Using a longitudinal repeated-measure design, 29 patients with implantable cardioverter defibrillators completed the Profile of Mood States-Short Form Japanese Version questionnaire before discharge and 1, 4, 7, and 13 months after implantation. One month after discharge, the mood states of the patients with implantable cardioverter defibrillators improved. From 7 to 13 months after discharge, moods deteriorated; 13 months after discharge, moods were equivalent to those at the time of discharge. No relationship with defibrillation experience was detected in this study, but employment, age, sex, and lack of experience of syncopal attack were factors related to poor mood states for patients with implantable cardioverter defibrillators. Therefore, Japanese patients with implantable cardioverter defibrillators with any factor deteriorating their mood state should be monitored so that their mood state does not deteriorate again between six months and one year after implantation.

  5. Cognitive profile of patients with burning mouth syndrome in the Japanese population.

    PubMed

    Matsuoka, Hirofumi; Himachi, Mika; Furukawa, Hirokazu; Kobayashi, Shiho; Shoki, Harumi; Motoya, Ryo; Saito, Masato; Abiko, Yoshihiro; Sakano, Yuji

    2010-07-01

    The present study investigated which cognitive characteristics, including cancer phobia, self-efficacy, pain-related catastrophizing, and anxiety sensitivity, affect burning mouth syndrome (BMS) symptoms in the Japanese population. A total of 46 BMS patients (44 women and 2 men; mean age, 59.98 +/- 9.57 years; range, 30-79 years) completed a battery of questionnaires, including measures of pain severity, oral-related quality of life (QOL), stress-response, pain-related catastrophizing, self-efficacy, anxiety sensitivity, and tongue cancer phobia. The Pain Catastrophizing Scale (PCS), General Self-Efficacy Scale (GSES), and Anxiety Sensitivity Index (ASI) scores in the BMS patients were compared with the scores of Japanese healthy participants (PCS, n = 449; GSES, n = 278; ASI, n = 9603) reported in previous studies. Catastrophizing and anxiety sensitivity were significantly higher in the BMS patients than in the healthy subjects (P < 0.001). In BMS patients, catastrophizing was significantly correlated with pain severity, stress-response, psychological disability, social disability, and handicap. Cancer phobia was significantly correlated with psychological disability and handicap. Since catastrophizing showed a higher correlation with BMS symptoms than cancer phobia, catastrophizing might be a more significant cognitive factor affecting symptoms than cancer phobia in BMS patients in the Japanese population.

  6. Opinions on Kampo and reasons for using it – results from a cross-sectional survey in three Japanese clinics

    PubMed Central

    2013-01-01

    Background Traditional Japanese Medicine (Kampo) is often used in Japan, but very little data on its users are available. We investigated who uses Kampo, the reasons and opinions for its use. Methods Questionnaire survey in three Japanese outpatient clinics offering Kampo in different settings: Kampo only, Kampo and traditional Chinese medicine, Kampo and Western medicine. Before seeing the doctor, patients were asked about socio-demographic data, medical history, experience with Kampo, general health-related opinions and behaviours, opinions about Western medicine and Kampo, and reasons for Kampo utilization. Descriptive statistics and predictors for Kampo use were calculated. Results A total of 354 questionnaires were completed. Participants were 50.97 ± 15.60 (mean ± SD) years of age, 68% were female. Of all patients, 73% (n = 202) were using Kampo currently and 84% (297) had taken Kampo before. Questions on general health-related opinions and behaviour revealed a strong environmental awareness. The most frequent indications for earlier Kampo use were: common cold (36%), gastrointestinal complaints (30%), oversensitivity to cold (“Hi’e-sho”; 29%), stress/anxiety (21%), and shoulder stiffness (20%). Kampo users suffered more often from chronic illnesses (OR 2.88 [1.48-5.58]). Beliefs in underlying philosophy (Wu Xing (adjusted OR 3.08, [1.11-8.55]), Ying and Yang (OR 2.57 [1.15-5.73], a holistic way of seeing the patient (OR 2.17 [1.53-3.08]), and in Kampo efficacy (OR 2.62 [1.66-4.13]) were positively associated with Kampo use. So was, interestingly, conviction of the efficacy of Western medicine (OR 1.87 [1.28-2.74]). Half of the patients had a general preference for a combination of Kampo and Western treatment. Conclusions Most patients visiting a clinic that also provided Kampo had previous experience with Kampo. Usage was associated with beliefs in philosophical Kampo concepts and its efficacy. PMID:23680097

  7. Home telemonitoring study for Japanese patients with heart failure (HOMES-HF): protocol for a multicentre randomised controlled trial

    PubMed Central

    Kotooka, Norihiko; Asaka, Machiko; Sato, Yasunori; Kinugasa, Yoshiharu; Nochioka, Kotaro; Mizuno, Atsushi; Nagatomo, Daisuke; Mine, Daigo; Yamada, Yoko; Eguchi, Kazuo; Hanaoka, Hideki; Inomata, Takayuki; Fukumoto, Yoshihiro; Yamamoto, Kazuhiro; Tsutsui, Hiroyuki; Masuyama, Tohru; Kitakaze, Masafumi; Inoue, Teruo; Shimokawa, Hiroaki; Momomura, Shin-ichi; Seino, Yoshihiko; Node, Koichi

    2013-01-01

    Introduction Despite the encouraging results from several randomised controlled trials (RCTs) and meta-analyses, the ability of home telemonitoring for heart failure (HF) to improve patient outcomes remains controversial as a consequence of the two recent large-scale RCTs. However, it has been suggested that there is a subgroup of patients with HF who may benefit from telemonitoring. The aim of the present study was to investigate whether an HF management programme using telemonitoring could improve outcomes in patients with HF under the Japanese healthcare system. Methods and analysis The Home Telemonitoring Study for Japanese Patients with Heart Failure (HOMES-HF) study is a prospective, multicentre RCT to investigate the effectiveness of home telemonitoring on the primary composite endpoint of all-cause death and rehospitalisation due to worsening HF in recently admitted HF patients (aged 20 and older, New York Heart Association classes II–III). The telemonitoring system is an automated physiological monitoring system including body weight, blood pressure and pulse rate by full-time nurses 7 days a week. Additionally, the system was designed to make it a high priority to support patient's self-care instead of an early detection of HF decompensation. A total sample size of 420 patients is planned according to the Schoenfeld and Richter method. Eligible patients are randomly assigned via a website to either the telemonitoring group or the usual care group by using a minimisation method with biased-coin assignment balancing on age, left ventricular ejection fraction and a history of ischaemic heart disease. Participants will be enrolled until August 2013 and followed until August 2014. Time to events will be estimated using the Kaplan-Meier method, and HRs and 95% CIs will be calculated using the Cox proportional hazards models with stratification factors. Trial Registration: The study is registered at UMIN Clinical Trials Registry (UMIN000006839). PMID

  8. Systematic Validation of RNF213 Coding Variants in Japanese Patients With Moyamoya Disease.

    PubMed

    Moteki, Yosuke; Onda, Hideaki; Kasuya, Hidetoshi; Yoneyama, Taku; Okada, Yoshikazu; Hirota, Kengo; Mukawa, Maki; Nariai, Tadashi; Mitani, Shohei; Akagawa, Hiroyuki

    2015-05-11

    A founder variant of RNF213, p.R4810K (c.14429G>A, rs112735431), was recently identified as a major genetic risk factor for moyamoya disease (MMD) in Japan. Although the association of p.R4810K was reported to be highly significant and reproducible, the disease susceptibility of other RNF213 variants remains largely unknown. In the present study, we systematically evaluated the coding variants detected in Japanese patients and controls for associations with MMD. To detect variants of RNF213, all coding exons were sequenced in 27 Japanese MMD patients without p.R4810K. We also validated all previously reported variants in our case-control samples and tested for associations in combination with previous Japanese study cohorts, including the 1000 Genomes Project data set, as population-based controls. Forty-six missense variants other than p.R4810K were identified among 370 combined patients and 279 combined controls in Japan. Sixteen of 46 variants were polymorphisms with minor allele frequency >1%, and, after conditioning on the p.R4810K genotype, were not associated with MMD. We conducted a variable threshold test using Combined Annotation-Dependent Depletion on the remaining 30 rare variants (minor allele frequency <1%), and the results showed that the frequency of potentially functional variants was significantly higher in patients than in controls (permutation, minimum P=0.045). Not only p.4810K but also other functional missense variants of RNF213 conferred susceptibility to MMD. Our analysis also revealed that ≈20% of Japanese MMD patients did not harbor susceptibility variants of RNF213, indicating the presence of other susceptibility genes for MMD. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  9. Does the treatment of type 2 diabetes mellitus with the DPP-4 inhibitor vildagliptin reduce HbA1c to a greater extent in Japanese patients than in Caucasian patients?

    PubMed

    Foley, James E; Bhosekar, Vaishali; Kawamori, Ryuzo

    2016-01-01

    Previous work suggests that Japanese patients with type 2 diabetes mellitus (T2DM) may respond more favorably to a DPP-4 (dipeptidyl peptidase-4) inhibitor than Caucasians. We aimed to compare the efficacy of the DPP-4 inhibitor vildagliptin (50 mg twice daily [bid]) between Japanese and Caucasian populations. This analysis pooled data from 19 studies of drug-naïve patients with T2DM who were treated for 12 weeks with vildagliptin 50 mg bid as monotherapy. The pool comprised Japanese patients (n=338) who had been treated in Japan and Caucasian patients (n=1,275) who were treated elsewhere. Change from baseline (Δ) in glycated hemoglobin (HbA1c) at 12 weeks (in millimoles per mole) versus baseline HbA1c (both in percentage National Glycohemoglobin Standardization Program units [NGSP%] and millimoles per mole) for each population was reported. Universal HbA1c in millimoles per mole was calculated from either the Japanese Diabetes Society or the NGSP% HbA1c standards. At baseline, mean values for Japanese and Caucasian patients, respectively, were as follows: age, 59 years and 56 years; % male, 69% and 57%. The average HbA1c was reduced from 7.90% to 6.96% (Japanese Diabetes Society) and from 8.57% to 7.50% (United States National Glycohemoglobin Standardization Program), while HbA1c was reduced from 63 mmol/mol to 53 mmol/mol and from 70 mmol/mol to 58 mmol/mol in Japanese and Caucasians, respectively. ΔHbA1c increased with increasing baseline in both populations. The slopes were the same (0.41, r (2)=0.36; and 0.41, r (2)=0.15), and the intercepts were 15.4 mmol/mol and 17.2 mmol/mol, respectively. In Japanese patients, mean ΔHbA1c was greater by 1.7 mmol/mol (0.2% NGSP HbA1c) at any given baseline HbA1c than in Caucasians (P=0.01). The present pooled analysis suggests that Japanese patients respond better to vildagliptin treatment compared with Caucasians. However, when glycemic control was corrected by using the same glycemic standard, the difference in HbA1c

  10. Single fecal microbiota transplantation failed to change intestinal microbiota and had limited effectiveness against ulcerative colitis in Japanese patients

    PubMed Central

    Mizuno, Shinta; Nanki, Kosaku; Matsuoka, Katsuyoshi; Saigusa, Keiichiro; Ono, Keiko; Arai, Mari; Sugimoto, Shinya; Kiyohara, Hiroki; Nakashima, Moeko; Takeshita, Kozue; Naganuma, Makoto; Suda, Wataru; Hattori, Masahira

    2017-01-01

    Background/Aims Recent developments in analytical techniques including next-generation sequencing have clarified the correlation between intestinal microbiota and inflammatory bowel disease. Fecal microbiota transplantation (FMT) for patients with ulcerative colitis (UC) is proposed as a potential approach to resolving their dysbiosis; however, its safety and efficacy have not been confirmed. This single-arm, open-label, non-randomized study aimed to evaluate the safety and efficacy of FMT for Japanese patients with UC as the first registered clinical trial in Japan. Methods We enrolled 10 patients with active UC despite medical therapy. The donors were the patients' relatives and were carefully screened for infectious diseases. Fecal material was administered via colonoscopy, and the primary endpoint was the presence or absence of serious adverse events related to FMT. The secondary endpoint was a change in partial Mayo score at 12 weeks post-FMT. Scores ≤2 were considered a clinical response. Fecal samples were collected to follow changes in gut microbiota, while extracted complementary DNA were analyzed by a next-generation sequencer. We obtained written informed consent from all patients and donors. This study was approved by our Institutional Review Board and is registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN 000012814). Results Five patients with moderate disease and five with severe disease were enrolled. No severe adverse effects were observed. One patient achieved clinical response; however, none of the patients' microbiota diversity recovered to the donor levels. Conclusions The use of single FMT for UC was safe; however, we failed to show its clinical efficacy and potential to change the intestinal microbiota. PMID:28239315

  11. [Exhaled and nasal nitric oxide in patients with Japanese cedar pollinosis and effects of nasal steroids].

    PubMed

    Miyazaki, Y

    1999-12-01

    Nitric oxide (NO) is produced by the action of NO synthase (NOS) using L-arginine as a substrate in various cells and found in air exhaled by humans. Previous studies suggest that almost all exhaled NO is derived from the upper airways and increases in patients with untreated asthma and allergic rhinitis. Exhaled NO is inhibited by treatment with inhalation of steroids that may be caused by inhibition of inducible nitric oxide synthase (iNOS). The purpose of this study is to determine whether exhaled and nasal NO increases in patients with Japanese cedar pollinosis compared with nonallergic healthy subjects, and whether it is affected by treatment with nasal steroids. Furthermore, we investigated its relation to nasal function and allergic rhinitis. 10 patients with Japanese cedar pollinosis and 5 healthy normal subjects were tested. All subjects had no history of respiratory infection for at least 2 weeks and did not smoke. Exhaled NO was collected in a sampling bag from oral and nasal breathing, and nasal NO was sampled directly from the nasal cavity. Both were measured by a chemiluminescence NO analyzer, ML9841, at a detection limit of 1 part per billion (ppb). Subjects used nasal steroids for 2 weeks and were measured similarly afterwards. NO concentrations in nasal air and air exhaled from the nose in patients with Japanese cedar pollinosis (277.9 +/- 59.5 ppb, 34.4 +/- 3.9 ppb, n = 10) were higher than the normal subjects (153.3 +/- 30.6 ppb, 19.9 +/- 3.4 ppb, n = 5) (p < 0.05). NO exhaled from the mouth was not significantly different between patients (20.5 +/- 4.9 ppb) and normal subjects (23.7 +/- 2.6 ppb). In patients with Japanese cedar pollinosis, the concentration of nasal NO and nasal exhaled NO were significantly decreased after treatment with nasal steroids (144.0 +/- 21.0 ppb, 26.1 +/- 3.0 ppb) (p < 0.01, p < 0.05), but there was no change in oral exhaled NO (17.2 +/- 3.3 ppb). In normal subjects, oral (22.5 +/- 5.3 ppb), nasal exhaled NO (19

  12. Phase II study of lanreotide autogel in Japanese patients with unresectable or metastatic well-differentiated neuroendocrine tumors.

    PubMed

    Ito, Tetsuhide; Honma, Yoshitaka; Hijioka, Susumu; Kudo, Atsushi; Fukutomi, Akira; Nozaki, Akira; Kimura, Yasutoshi; Motoi, Fuyuhiko; Isayama, Hiroyuki; Komoto, Izumi; Hisamatsu, Seiichi; Nakajima, Akihiro; Shimatsu, Akira

    2017-08-01

    Background Lanreotide is a long-acting somatostatin analog with demonstrated efficacy against enteropancreatic neuroendocrine tumor (NET) in the phase III (CLARINET) study. Materials and Methods In this single-arm study, Japanese patients with grade (G) 1/G2 NET received lanreotide (120 mg/4 weeks) for 48 weeks. Those who completed the study were enrolled in a long-term extension study. The primary endpoint was the clinical benefit rate (CBR) defined as a complete response, partial response (PR), or stable disease (SD) over 24-weeks. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, and pharmacokinetics. Results Thirty-two patients were recruited at 10 sites. The full analysis set (FAS) comprised 28 patients. Primary tumors were located in pancreas (12 patients), foregut (non-pancreas, lung; 1), midgut (2), hindgut (8), and unknown (5). Four patients had gastrinoma of the functional NET, and 3 had multiple endocrine neoplasia type 1. In the FAS, 39.3% had progressive disease at baseline. The CBR at 24 weeks was 64.3% (95% confidence interval; CI: 44.1-81.4), and median PFS was 36.3 weeks (95% CI: 24.1-53.1). PR was confirmed in 1 patient at 60 weeks during the extension study (ORR: 3.6%). Frequent adverse events related to lanreotide included injection site induration (28.1%), faeces pale (18.8%), flatulence (12.5%), and diabetes mellitus (12.5%). Conclusions The efficacy and safety of lanreotide in this study indicated its usefulness as a treatment option for Japanese NET patients. JapicCTI-132,375, JapicCTI-142,698.

  13. Writing errors as a result of frontal dysfunction in Japanese patients with amyotrophic lateral sclerosis.

    PubMed

    Tsuji-Akimoto, Sachiko; Hamada, Shinsuke; Yabe, Ichiro; Tamura, Itaru; Otsuki, Mika; Kobashi, Syoji; Sasaki, Hidenao

    2010-12-01

    Loss of communication is a critical problem for advanced amyotrophic lateral sclerosis (ALS) patients. This loss of communication is mainly caused by severe dysarthria and disability of the dominant hand. However, reports show that about 50% of ALS patients have mild cognitive dysfunction, and there are a considerable number of case reports on Japanese ALS patients with agraphia. To clarify writing disabilities in non-demented ALS patients, eighteen non-demented ALS patients and 16 controls without neurological disorders were examined for frontal cognitive function and writing ability. To assess writing errors statistically, we scored them on their composition ability with the original writing error index (WEI). The ALS and control groups did not differ significantly with regard to age, years of education, or general cognitive level. Two patients could not write a letter because of disability of the dominant hand. The WEI and results of picture arrangement tests indicated significant impairment in the ALS patients. Auditory comprehension (Western Aphasia Battery; WAB IIC) and kanji dictation also showed mild impairment. Patients' writing errors consisted of both syntactic and letter-writing mistakes. Omission, substitution, displacement, and inappropriate placement of the phonic marks of kana were observed; these features have often been reported in Japanese patients with agraphia resulted from a frontal lobe lesion. The most frequent type of error was an omission of kana, the next most common was a missing subject. Writing errors might be a specific deficit for some non-demented ALS patients.

  14. Modified docetaxel, cisplatin and capecitabine for stage IV gastric cancer in Japanese patients: A feasibility study

    PubMed Central

    Maeda, Osamu; Matsuoka, Ayumu; Miyahara, Ryoji; Funasaka, Kohei; Hirooka, Yoshiki; Fukaya, Masahide; Nagino, Masato; Kodera, Yasuhiro; Goto, Hidemi; Ando, Yuichi

    2017-01-01

    AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients. METHODS We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage IV gastric cancer. In particular, 30 or 40 mg/m2 of docetaxel on day 1, 60 mg/m2 of cisplatin on day 1, and 2000 mg/m2 of capecitabine for 2 wk were administered every three weeks. RESULTS Three patients were treated with modified DCX (mDCX) with 30 mg/m2 docetaxel, and five patients were treated with this regimen with 40 mg/m2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes. CONCLUSION mDCX was well tolerated by Japanese patients with stage IV gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery. PMID:28246483

  15. Association between SCO2 mutation and extreme myopia in Japanese patients.

    PubMed

    Wakazono, Tomotaka; Miyake, Masahiro; Yamashiro, Kenji; Yoshikawa, Munemitsu; Yoshimura, Nagahisa

    2016-07-01

    To investigate the role of SCO2 in extreme myopia of Japanese patients. In total, 101 Japanese patients with extreme myopia (axial length of ≥30 mm) OU at the Kyoto University Hospital were included in this study. Exon 2 of SCO2 was sequenced by conventional Sanger sequencing. The detected variants were assessed using in silico prediction programs: SIFT, PolyPhen-2 and MutationTaster. To determine the frequency of the mutations in normal subjects, we referred to the 1000 Genomes Project data and the Human Genetic Variation Database (HGVD) in the Human Genetic Variation Browser. The average age of the participants was 62.9 ± 12.7 years. There were 31 males (30.7 %) and 70 females. Axial lengths were 31.76 ± 1.17 mm OD and 31.40 ± 1.07 mm OS, and 176 eyes (87.6 %) out of 201 eyes had myopic maculopathy of grade 2 or more. Among the 101 extremely myopic patients, one mutation (c.290 C > T;p.Ala97Val) in SCO2 was detected. This mutation was not found in the 1000 Genomes Project data or HGVD data. Variant type of the mutation was nonsynonymous. Although the SIFT prediction score was 0.350, the PolyPhen-2 probability was 0.846, thus predicting its pathogenicity to be possibly damaging. MutationTaster PhyloP was 1.268, suggesting that the mutation is conserved. We identified one novel possibility of an extreme myopia-causing mutation in SCO2. No other disease-causing mutation was found in 101 extremely myopic Japanese patients, suggesting that SCO2 plays a limited role in Japanese extreme myopia. Further investigation is required for better understanding of extreme myopia.

  16. Clinical characterization and identification of duplication breakpoints in a Japanese family with Xq28 duplication syndrome including MECP2.

    PubMed

    Fukushi, Daisuke; Yamada, Kenichiro; Nomura, Noriko; Naiki, Misako; Kimura, Reiko; Yamada, Yasukazu; Kumagai, Toshiyuki; Yamaguchi, Kumiko; Miyake, Yoshishige; Wakamatsu, Nobuaki

    2014-04-01

    Xq28 duplication syndrome including MECP2 is a neurodevelopmental disorder characterized by axial hypotonia at infancy, severe intellectual disability, developmental delay, mild characteristic facial appearance, epilepsy, regression, and recurrent infections in males. We identified a Japanese family of Xq28 duplications, in which the patients presented with cerebellar ataxia, severe constipation, and small feet, in addition to the common clinical features. The 488-kb duplication spanned from L1CAM to EMD and contained 17 genes, two pseudo genes, and three microRNA-coding genes. FISH and nucleotide sequence analyses demonstrated that the duplication was tandem and in a forward orientation, and the duplication breakpoints were located in AluSc at the EMD side, with a 32-bp deletion, and LTR50 at the L1CAM side, with "tc" and "gc" microhomologies at the duplication breakpoints, respectively. The duplicated segment was completely segregated from the grandmother to the patients. These results suggest that the duplication was generated by fork-stalling and template-switching at the AluSc and LTR50 sites. This is the first report to determine the size and nucleotide sequences of the duplicated segments at Xq28 of three generations of a family and provides the genotype-phenotype correlation of the patients harboring the specific duplicated segment.

  17. Screening of the LIX1 gene in Japanese and Malaysian patients with SMA and/or SMA-like disorder.

    PubMed

    Sasongko, Teguh Haryo; Gunadi; Yusoff, Surini; Atif, Amin Baig; Fatemeh, Hayati; Rani, Abdulqawee; Marini, Marzuki; Ab Aziz, Che Badariah; Zabidi-Hussin, Z A M H; Nishio, Hisahide; Zilfalil, Bin Alwi

    2010-05-01

    The majority of spinal muscular atrophy (SMA) patients showed homozygous deletion or other mutations of SMN1. However, the genetic etiology of a significant number of SMA patients has not been clarified. Recently, mutation in the gene underlying cat SMA, limb expression 1 (LIX1), has been reported. Similarity in clinical and pathological features of cat and human SMA may give an insight into possible similarity of the genetic etiology. In this study, we screened for a mutation in LIX1 using direct DNA sequencing in our SMA and/or SMA-like patients who retained SMN1. A total of 33 patients were enrolled in this study, of which 22 were Japanese and 11 were Malaysians. All these patients possessed at least two copies of SMN1. We did not identify any pathogenic mutations in the coding regions or splice sites of LIX1 in the patients. In addition, we described a polymorphism within LIX1 intron 3, c.387+107A>T. We found that A-allele is significantly more frequent in SMA patients compared to normal individuals. Molecular genetic analysis of our SMA and/or SMA-like patients suggests that LIX1 is not associated with the development of their disorders. However, the number of patients analyzed in this study was very limited, and a larger study with bigger sample size is needed to confirm this result. Copyright 2009 Elsevier B.V. All rights reserved.

  18. An exploratory factor analysis of existential suffering in Japanese terminally ill cancer patients.

    PubMed

    Morita, T; Tsunoda, J; Inoue, S; Chihara, S

    2000-01-01

    To determine an underlying factorial structure of existential distress in Japanese terminally ill cancer patients, a principal components analysis was performed on 162 Japanese hospice inpatients. Existential distress commonly identified was dependency (39%), meaninglessness in present life (37%), hopelessness (37%), burden on others (34%), loss of social role functioning (29%), and feeling emotionally irrelevant (28%). By a factor analysis, three primary components accounted for 66% of the variance. 'Dependency' and 'loss of social role functioning' loaded highly on the first factor, which was interpreted as 'loss of autonomy'. 'Burden on others' and 'feeling emotionally irrelevant' loaded highly on the second component interpreted as 'lowered self-esteem', while 'hopelessness' loaded highly on the third factor. On the other hand, 'meaninglessness in present life' loaded equally on all three components, and was significantly associated with other distress. In conclusion, existential suffering of Japanese terminally ill cancer patients has three principal components: loss of autonomy, lowered self-esteem, and hopelessness. It is also suggested that meaninglessness in present life would be an underlying theme in patients' spirituality.

  19. Wolfram Syndrome in the Japanese Population; Molecular Analysis of WFS1 Gene and Characterization of Clinical Features

    PubMed Central

    Inoue, Hiroshi; Okuya, Shigeru; Ohta, Yasuharu; Akiyama, Masaru; Taguchi, Akihiko; Kora, Yukari; Okayama, Naoko; Yamada, Yuichiro; Wada, Yasuhiko; Amemiya, Shin; Sugihara, Shigetaka; Nakao, Yuzo; Oka, Yoshitomo; Tanizawa, Yukio

    2014-01-01

    Background Wolfram syndrome (WFS) is a recessive neurologic and endocrinologic degenerative disorder, and is also known as DIDMOAD (Diabetes Insipidus, early-onset Diabetes Mellitus, progressive Optic Atrophy and Deafness) syndrome. Most affected individuals carry recessive mutations in the Wolfram syndrome 1 gene (WFS1). However, the phenotypic pleiomorphism, rarity and molecular complexity of this disease complicate our efforts to understand WFS. To address this limitation, we aimed to describe complications and to elucidate the contributions of WFS1 mutations to clinical manifestations in Japanese patients with WFS. Methodology The minimal ascertainment criterion for diagnosing WFS was having both early onset diabetes mellitus and bilateral optic atrophy. Genetic analysis for WFS1 was performed by direct sequencing. Principal Findings Sixty-seven patients were identified nationally for a prevalence of one per 710,000, with 33 patients (49%) having all 4 components of DIDMOAD. In 40 subjects who agreed to participate in this investigation from 30 unrelated families, the earliest manifestation was DM at a median age of 8.7 years, followed by OA at a median age of 15.8 years. However, either OA or DI was the first diagnosed feature in 6 subjects. In 10, features other than DM predated OA. Twenty-seven patients (67.5%) had a broad spectrum of recessive mutations in WFS1. Two patients had mutations in only one allele. Eleven patients (27.5%) had intact WFS1 alleles. Ages at onset of both DM and OA in patients with recessive WFS1 mutations were indistinguishable from those in patients without WFS1 mutations. In the patients with predicted complete loss-of-function mutations, ages at the onsets of both DM and OA were significantly earlier than those in patients with predicted partial-loss-of function mutations. Conclusion/Significance This study emphasizes the clinical and genetic heterogeneity in patients with WFS. Genotype-phenotype correlations may exist in patients

  20. Idiopathic Intracranial Hypertension in a Prepubertal Pediatric Japanese Patient Complicated by Severe Papilledema

    PubMed Central

    Oka, Akiko; Ikesugi, Kengo; Kondo, Mineo

    2016-01-01

    Purpose To report a rare case of idiopathic intracranial hypertension (IIH) in a prepubertal pediatric patient. Case Report The patient was an 11-year-old Japanese boy. Initially, an ophthalmologist found severe papilledema, and the patient was diagnosed with IIH. He was unresponsive to conservative therapy, and a ventriculoperitoneal shunt was inserted in the Neurosurgery Department because the visual impairment was severe. Twelve months after the shunt, the improvement in vision was limited due to optic disc atrophy. Conclusion Ophthalmologists need to be more aware of II, especially in cases with severe papilledema that can lead to permanent reduction of vision. PMID:27065853

  1. Successful intermuscular implantation of subcutaneous implantable cardioverter defibrillator in a Japanese patient with pectus excavatum.

    PubMed

    Kondo, Yusuke; Ueda, Marehiko; Winter, Joachim; Nakano, Miyo; Nakano, Masahiro; Ishimura, Masayuki; Miyazawa, Kazuo; Tateno, Kaoru; Kobayashi, Yoshio

    2017-02-01

    The entirely subcutaneous implantable cardioverter-defibrillator (ICD) system was developed to provide a life-saving defibrillation therapy that does not affect the heart and vasculature. The subcutaneous ICD is preferred over the transvenous ICD for patients with a history of recurrent infection presenting major life-threatening rhythms. In this case report, we describe the first successful intermuscular implantation of a completely subcutaneous ICD in a Japanese patient with pectus excavatum. There were no associated complications with the device implantation or lead positioning. Further, the defibrillation threshold testing did not pose any problem with the abnormal anatomy of the patient.

  2. Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes.

    PubMed

    Fujimoto, Kanta; Hamamoto, Yoshiyuki; Honjo, Sachiko; Kawasaki, Yukiko; Mori, Kanako; Tatsuoka, Hisato; Matsuoka, Atsuko; Wada, Yoshiharu; Ikeda, Hiroki; Fujikawa, Jun; Koshiyama, Hiroyuki

    2013-02-01

    We retrospectively examined the frequency of bladder cancer in Japanese patients with type 2 diabetes in relation to use of pioglitazone. Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72]).

  3. Reliability and validity of the Japanese version of the selective control assessment of the lower extremity tool among patients with spastic cerebral palsy

    PubMed Central

    Kusumoto, Yasuaki; Hanao, Mami; Takaki, Kenji; Matsuda, Tadamitsu; Nitta, Osamu

    2016-01-01

    [Purpose] The aim of this study was to translate the Selective Control Assessment of the Lower Extremity (SCALE) tool from English to Japanese and to assess the reliability and validity of the Japanese version of the SCALE (SCALE-J) tool in Japanese patients with spastic cerebral palsy. [Subjects and Methods] The SCALE tool was translated into Japanese in accordance with the published guidelines. In total, 55 patients with spastic cerebral palsy were enrolled in the present study. Reliability by internal consistency (Cronbach’s α), intrarater reliability, inter-rater reliability, and convergent validity by comparing Gross Motor Function Classification System (GMFCS) scores were examined. [Results] The Cronbach’s α value of the SCALE-J tool was 0.97–0.98, whereas that of the intrarater and inter-rater reliability ranged from 0.93 to 0.96. The Spearman correlation coefficient revealed a good relationship between the SCALE tool and the GMFCS. [Conclusion] The SCALE-J tool was found to be reliable and valid; therefore, the SCALE tool may be useful for evaluation in clinical practice. PMID:28174443

  4. Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: a phase II study.

    PubMed

    Yamazaki, Naoya; Kiyohara, Yoshio; Uhara, Hisashi; Uehara, Jiro; Fujimoto, Manabu; Takenouchi, Tatsuya; Otsuka, Masaki; Uchi, Hiroshi; Ihn, Hironobu; Minami, Hironobu

    2017-03-25

    Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation via overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has demonstrated promising anti-cancer activity in various cancers. We conducted a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty-four patients with stage III/IV or recurrent melanoma were enrolled and received intravenous nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee-assessed overall response rate was 34.8% (90% confidence interval [CI]: 20.8, 51.9), and the overall survival rate at 18 months was 56.5% (90% CI: 38.0, 71.4). Treatment-related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype and that patients with treatment-related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab demonstrated favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. This article is protected by copyright. All rights reserved.

  5. Being overweight influences the development of hepatic dysfunction in Japanese patients with non-small-cell lung cancer undergoing cytotoxic chemotherapy.

    PubMed

    Fujiwara, Yoshiro; Kiura, Katsuyuki; Hotta, Katsuyuki; Tabata, Masahiro; Takigawa, Nagio; Tanimoto, Mitsune

    2007-03-01

    The aim of this study was to identify risk factors for hepatic dysfunction during cytotoxic chemotherapy in Japanese patients with non-small-cell lung cancer (NSCLC). We retrospectively reviewed the medical records of patients with NSCLC who received cytotoxic chemotherapy at Okayama University Hospital between January 2003 and March 2006. "Overweight" was defined as a body mass index (BMI) of 25 or more, according to the World Health Organization (WHO) criteria. We investigated the incidence and pattern of hepatic dysfunction during chemotherapy and evaluated the possible associations between hepatic dysfunction and several clinical factors, including BMI. Of the 155 Japanese patients enrolled in this study, 19 (12%) were overweight. Grade 2 or worse hepatic dysfunction was observed in 5 of the 19 overweight patients (26%) but in only 13 of the 136 non-overweight patients (10%). A multivariate analysis demonstrated that a higher BMI significantly increased the risk of grade 2 or worse hepatic dysfunction after the initiation of cytotoxic chemotherapy (odds ratio=4.04, 95% confidence intervals: 1.13-14.5, p=0.032). Our data suggest that being overweight can influence the development of hepatic dysfunction in Japanese patients receiving cytotoxic chemotherapy for the treatment of NSCLC, although further investigation is required.

  6. Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with parathyroid cancer and intractable primary hyperparathyroidism.

    PubMed

    Takeuchi, Yasuhiro; Takahashi, Shunsuke; Miura, Daishu; Katagiri, Makoto; Nakashima, Noriaki; Ohishi, Hiroko; Shimazaki, Ryutaro; Tominaga, Yoshihiro

    2016-11-21

    Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated until the albumin-corrected serum calcium concentration decreased to 10.0 mg/dL or less or until dose escalation was considered not necessary or feasible. Serum calcium concentration at the baseline was 12.1 ± 1.3 mg/dL (mean ± standard deviation; range 10.4-14.6 mg/dL) and decreased to 10.1 ± 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At the end of the titration phase, at least a 1 mg/dL reduction in serum calcium concentration from the baseline was observed in five patients (three with carcinoma and two with PHPT), and it decreased to the normocalcemic range in five patients (three with carcinoma and two with PHPT). Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder. Cinacalcet effectively relieved hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and might be effective in those with intractable PHPT. The drug might be tolerable and safe at a dosage of at most 75 mg three times a day.

  7. Development of a questionnaire to evaluate asthma control in Japanese asthma patients.

    PubMed

    Tohda, Yuji; Hozawa, Soichiro; Tanaka, Hiroshi

    2017-08-31

    The asthma control questionnaires used in Japan are Japanese translations of those developed outside Japan, and have some limitations; a questionnaire designed to optimally evaluate asthma control levels for Japanese may be necessary. The present study was conducted to validate the Japan Asthma Control Survey (JACS) questionnaire in Japanese asthma patients. A total of 226 adult patients with mild to severe persistent asthma were enrolled and responded to the JACS questionnaire, asthma control questionnaire (ACQ), and Mini asthma quality of life questionnaire (Mini AQLQ) at Weeks 0 and 4. The reliability, validity, and sensitivity/responsiveness of the JACS questionnaire were evaluated. The intra-class correlation coefficients (ICCs) were within the range of 0.55-0.75 for all JACS scores, indicating moderate/substantial reproducibility. For internal consistency, Cronbach's alpha coefficients ranged from 0.76 to 0.92 in total and subscale scores, which were greater than the lower limit of internal consistency. As for factor validity, the cumulative contribution ratio of four main factors was 0.66. For criterion-related validity, the correlation coefficients between the JACS total score and ACQ5, ACQ6, and Mini AQLQ scores were -0.78, -0.78, and 0.77, respectively, showing a significant correlation (p < 0.0001). The JACS questionnaire was validated in terms of reliability and validity. It will be necessary to evaluate the therapeutic efficacy measured by the JACS questionnaire and calculate cutoff values for the asthma control status in a higher number of patients. UMIN000016589. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  8. The lipid profiles in Japanese patients with schizophrenia treated with antipsychotic agents.

    PubMed

    Watanabe, Junzo; Suzuki, Yutaro; Sugai, Takuro; Fukui, Naoki; Ono, Shin; Tsuneyama, Nobuto; Saito, Mami; Someya, Toshiyuki

    2012-01-01

    Antipsychotic-treated schizophrenia patients are susceptible to dyslipidemia. However, the results of previous studies of North American and UK populations including various races have been contradictory with regard to which lipid measure was the most affected in patients with schizophrenia taking antipsychotic agents. The aim of this study was to investigate the effect of schizophrenia patients receiving antipsychotic agents on each lipid measure in a Japanese population. The samples included 136 control individuals and 157 patients with schizophrenia treated with antipsychotic agents. Age, gender distribution and body mass index (BMI) of the controls were matched with the patients. The high-density lipoprotein cholesterol (HDL-cholesterol) levels were significantly lower in patients than in the control subjects (P<.001). However, there were no significant differences in either the low-density lipoprotein cholesterol (LDL-cholesterol) or triglyceride levels between the patient and control groups. We performed a multiple linear regression analysis, and schizophrenia receiving antipsychotics was an independent predictor of decreased HDL-cholesterol. An increased BMI, male gender and cigarette smoking were also major predictors of a decreased HDL-cholesterol level (r(2)=0.42, P<.001). At least in Japanese with schizophrenia receiving antipsychotic agents, the HDL-cholesterol levels should be closely monitored in all patients, even those who are not obese or do not smoke, to decrease their risk of cardiovascular disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Patterns of stress coping and depression among patients with head and neck cancer: A Japanese cross-sectional study.

    PubMed

    Ichikura, Kanako; Yamashita, Aya; Sugimoto, Taro; Kishimoto, Seiji; Matsushima, Eisuke

    2017-08-31

    Patients with head and neck cancer (HNC) experience many stressful problems with breathing, eating, swallowing, and/or speaking. The aim of this study was to (a) identify the clusters of HNC patients based on their stress coping strategies and (b) evaluate the differences in clinical data and depression among the identified HNC patients' coping clusters. We conducted a single-center, cross-sectional study with self-completed questionnaires for patients with HNC between April and August 2013. We measured stress coping (an abbreviated version of the COPE Inventory: Brief COPE) and depression (the Japanese version of the Beck Depression Inventory-II: BDI-II). Of the 116 patients who completed all the questionnaires, 81 (69.8%) participants were 60 to 79 years old and 105 (90.5%) were men. Cluster analysis based on the standardized z score of Brief COPE showed that patients were classified into 3 clusters, labeled "dependent coping," "problem-focused coping," and "resigned coping." The ANOVA revealed that depression (BDI score) was significantly higher in the dependent-coping cluster compared with the problem-focused coping. This study indicates that patients with a dependent-coping pattern may account for the largest HNC population and are likely to suffer from depression. Dependent coping includes smoking, drinking, seeking support, or engaging self-distraction. In the future, we should develop psychological intervention programs focused on coping strategies and enhancement of the support system for patients with HNC. Copyright © 2017 John Wiley & Sons, Ltd.

  10. The Aggravation of Depression with Aging in Japanese Patients with Subacute Myelo-optico-neuropathy (SMON).

    PubMed

    Konishi, Tetsuro; Hayashi, Kaori; Sugiyama, Hiroshi

    2017-08-15

    Objective We attempted to clarify the factors related to the aggravation of depression in patients with subacute myelo-optico-neuropathy (SMON) caused by clioquinol intoxication more than 35 years previously. Methods We investigated changes in the depressive mental states that occurred with aging in 19 Japanese SMON patients (mean age, 78.3 years; range, 66-89 years) according to their scores on the Japanese version of the Zung Self-rating Depression Scale (SDS), which were obtained 3-10 years previously and their current scores. The depressive state was further evaluated using simultaneous semi-structured interviews. Results The depressive mental states of 6 patients, whose current total SDS scores had increased by ≥10% in comparison to the previous score, were considered to have been aggravated with aging. The mean current total SDS score of these six patients was significantly higher than the mean score of the 13 patients whose conditions were not aggravated. Among the 20 SDS questionnaires, the patients whose conditions were aggravated showed significantly higher scores in diurnal variation, sleep disturbance and weight loss. The semi-structured interviews revealed that physical disabilities due to the sequelae of SMON, a lack of acceptance of SMON, and a decline in social activities were important factors in the aggravation of their depressive mental states with aging. Conclusion The maintenance of social activities with public support was important for coping among Japanese SMON patients with a depressive mental state, especially those who could not walk independently or who could not go outside freely without assistance.

  11. Pharmacokinetics, efficacy, and safety of caspofungin in Japanese pediatric patients with invasive candidiasis and invasive aspergillosis.

    PubMed

    Mori, Masaaki; Imaizumi, Masue; Ishiwada, Naruhiko; Kaneko, Takashi; Goto, Hiroaki; Kato, Koji; Hara, Junichi; Kosaka, Yoshiyuki; Koike, Kazutoshi; Kawamoto, Hiroshi; Maeda, Naoko; Yoshinari, Tomoko; Kishino, Hiroyuki; Takahashi, Kenichi; Kawahara, Shizuko; Kartsonis, Nicholas A; Komada, Yoshihiro

    2015-06-01

    The antifungal agents approved in Japan for pediatric use are limited and many unapproved drugs are actually used without clear instruction for dosage. We investigated the pharmacokinetics of caspofungin for the treatment of invasive candidiasis and invasive aspergillosis in 20 Japanese pediatric patients using a pediatric-specific dosage based on body surface area. Caspofungin was administered intravenously over 60 min as 70 mg/m(2) on Day 1, followed by 50 mg/m(2) per day. Five or 4 point blood sampling were done in 15 patients on Day 4-5 to calculate AUC0-24 h. The geometric means (95% confidence interval) of C24 h and AUC0-24 h in the pediatric patients were 3.3(2.5, 4.4) μg/mL and 175.1 (139.3, 220.1) μg hr/mL, respectively, which were comparable to those in Japanese adult patients [3.2 (2.8, 3.5) μg/mL and 144.9 (131.7, 159.3) μg hr/mL, respectively]. Among the 20 patients, 10 (50%) had at least 1 drug-related adverse event which was considered related to caspofungin therapy. No drug-related serious adverse event and no death occurred. The most common drug-related adverse events were events relating to hepatic function (mainly increases in ALT and AST). The overall success in efficacy was observed in 13 of 20 patients. In conclusion, once daily administration of caspofungin (70 mg/m(2) on Day 1, followed by 50 mg/m(2) [maximum daily dose not to exceed 70 mg]), which is the same dosage being used in overseas, achieved sufficient drug exposure and a favorable efficacy and acceptable safety profile in Japanese pediatric patients with invasive fungal infections.

  12. Impact of diabetes mellitus on outcomes in Japanese patients undergoing coronary artery bypass grafting.

    PubMed

    Minakata, Kenji; Bando, Ko; Takanashi, Shuichiro; Konishi, Hiroaki; Miyamoto, Yoshihiro; Ueshima, Kenji; Sato, Tosiya; Ueda, Yuichi; Okita, Yutaka; Masuda, Izuru; Okabayashi, Hitoshi; Yaku, Hitoshi; Yasuno, Shinji; Muranaka, Hiroyuki; Kasahara, Masato; Miyata, Shigeki; Okamura, Yoshitaka; Nasu, Michihiro; Tanemoto, Kazuo; Arinaga, Koichi; Hisashi, Yosuke; Sakata, Ryuzo

    2012-05-01

    There have been no large-scale studies on the impact of diabetes mellitus (DM) on outcomes in Japanese patients undergoing coronary artery bypass grafting (CABG). A multi-institutional retrospective cohort study was conducted in 14 Japanese centers. All adult patients who underwent isolated CABG from 2007 to 2008 were included (n=1522, mean age: 68.5years). The definitions of DM were all patients admitted with diagnosis of DM and preoperative glycated hemoglobin (Hb) A1c≥6.5%. Univariate and multivariate analyses were performed to identify the risk of morbidity and mortality. There were 849 DM and 572 non-DM patients. Preoperative mean HbA1c were 7.1% in the DM group and 5.7% in the non-DM group (p<0.0001). Preoperative, intraoperative, and 3-day average postoperative blood glucose (BG) were 146mg/dl, 172mg/dl, and 168mg/dl in the DM group, and 103mg/dl, 140mg/dl, and 136mg/dl in the non-DM group (all p<0.0001). Although there were no significant differences in postoperative cardiovascular events, the incidence of infection was significantly higher in the DM group than in the non-DM group (9.2% vs 6.1%, p=0.036) on the univariate analysis. The all-cause death was also relatively higher in the DM group than in the non-DM group (2.1% vs 1.1%, p=0.12), and this was likely related to infection. DM patients had worse perioperative BG control, higher incidence of infection, and higher mortality than non-DM patients. These results indicate that perioperative BG control guidelines should be standardized to obtain better surgical outcomes in Japanese DM patients. Copyright © 2012. Published by Elsevier Ltd.

  13. HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions.

    PubMed

    Ikeda, Hiroko; Takahashi, Yukitoshi; Yamazaki, Etsuko; Fujiwara, Tateki; Kaniwa, Nahoko; Saito, Yoshiro; Aihara, Michiko; Kashiwagi, Mariko; Muramatsu, Masaaki

    2010-02-01

    Carbamazepine (CBZ) is frequently used for treating epilepsy, but this drug causes cutaneous adverse drug reactions (cADRs) that may range from mild to severe. It is reported recently that the human leukocyte antigen HLA-B*1502 is associated with Stevens-Johnson syndrome (SJS) induced by CBZ in Han Chinese. We examined HLA class I in 15 Japanese patients who fulfilled the diagnostic criteria for CBZ-induced cADRs (mild in 10 and severe = SJS in 5). HLA-B*1518, HLA-B*5901 and HLA-C*0704 alleles showed higher relative risks (above 10.0) for severe cADRs. The haplotype (HLA-A*2402-B*5901-C*0102) had high relative risk (16.09) for severe cADRs. In patients with severe cADRs, frequencies of HLA-A*1101, HLA-A*3303, HLA-B*1501, HLA-B*4403, HLA-B*5101, HLA-B*5201, HLA-C*0702, and HLA-C*1202 alleles are relatively lower than in the Japanese population. These data may suggest that HLA-B*5901 is one of the candidate markers for CBZ-induced SJS in Japanese.

  14. Significance of Kampo, Japanese Traditional Medicine, in the Treatment of Obesity: Basic and Clinical Evidence

    PubMed Central

    Yamakawa, Jun-ichi; Moriya, Junji; Takeuchi, Kenji; Nakatou, Mio; Motoo, Yoshiharu; Kobayashi, Junji

    2013-01-01

    The cause of obesity includes genetic and environmental factors, including cytokines derived from adipocytes (adipo-cytokines). Although drug therapy is available for obesity, it is highly risky. Our main focus in this review is on the traditional form of Japanese medicine, Kampo, in the treated of obesity. Two Kampo formulas, that is, bofutsushosan (防風通聖散) and boiogito (防己黄耆湯), are covered by the national health insurance in Japan for the treatment of obesity. Various issues related to their action mechanisms remain unsolved. Considering these, we described the results of basic experiments and presented clinical evidence and case reports on osteoarthritis as examples of clinical application of their two Kampo medicine. Traditional medicine is used not only for treatment but also for prevention. In clinical practice, it is of great importance to prove the efficacy of combinations of traditional medicine and Western medicine and the utility of traditional medicine in the attenuation of adverse effects of Western medicine. PMID:23662155

  15. Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever

    PubMed Central

    Yasunami, Michio; Nakamura, Hitomi; Agematsu, Kazunaga; Nakamura, Akinori; Yazaki, Masahide; Kishida, Dai; Yachie, Akihiro; Toma, Tomoko; Masumoto, Junya; Ida, Hiroaki; Koga, Tomohiro; Kawakami, Atsushi; Eguchi, Katsumi; Furukawa, Hiroshi; Nakamura, Tadashi; Nakamura, Minoru; Migita, Kiyoshi

    2015-01-01

    Objectives The genotype-phenotype correlation of MEFV remains unclear for the familial Mediterranean fever (FMF) patients, especially without canonical MEFV mutations in exon 10. The risk of FMF appeared to be under the influence of other factors in this case. The contribution of HLA polymorphisms to the risk of FMF was examined as strong candidates of modifier genes. Methods Genotypes of HLA-B and -DRB1 loci were determined for 258 mutually unrelated Japanese FMF patients, who satisfied modified Tel-Hashomer criteria, and 299 healthy controls. The effects of carrier status were evaluated for the risk of FMF by odds ratio (OR). The HLA effects were also assessed for clinical forms of FMF, subsets of FMF with certain MEFV genotypes and responsiveness to colchicine treatment. Results The carriers of B*39:01 were increased in the patients (OR = 3.25, p = 0.0012), whereas those of DRB1*15:02 were decreased (OR = 0.45, p = 0.00050), satisfying Bonferroni’s correction for multiple statistical tests (n = 28, p<0.00179). The protective effect of DRB1*15:02 was completely disappeared in the co-existence of B*40:01. The HLA effects were generally augmented in the patients without a canonical MEFV variant allele M694I, in accordance with the notion that the lower penetrance of the mutations is owing to the larger contribution of modifier genes in the pathogenesis, with a few exceptions. Further, 42.9% of 14 colchicine-resistant patients and 13.5% of 156 colchicine-responders possessed B*35:01 allele, giving OR of 4.82 (p = 0.0041). Conclusions The differential effects of HLA class I and class II polymorphisms were identified for Japanese FMF even in those with high-penetrance MEFV mutations. PMID:25974247

  16. Vascular Risk Factors and Internal Jugular Venous Flow in Transient Global Amnesia: A Study of 165 Japanese Patients.

    PubMed

    Himeno, Takahiro; Kuriyama, Masaru; Takemaru, Makoto; Kanaya, Yuhei; Shiga, Yuji; Takeshima, Shinichi; Takamatsu, Kazuhiro; Shimoe, Yutaka; Fukushima, Tomoko; Matsubara, Etsuro

    2017-10-01

    The etiology of transient global amnesia (TGA) remains unclear. We studied the pathophysiology of TGA in 165 Japanese patients. TGA was diagnosed in hospitalized patients from 2004 to 2015. We analyzed clinical characteristics, magnetic resonance imaging findings, and maximum intima-media thickness of the common carotid artery, and the reflux of internal jugular venous (IJV) flow by ultrasonography, and statistically compared patients with TGA with age-matched and sex-matched patients who have had a transient ischemic attack (TIA), small-vessel occlusion (SVO), and normal controls (each group, N = 165). Patients with TGA showed lower prevalence of vascular risk factors than patients with TIA and SVO did. Eleven patients (6.7%) had 2 episodes of TAG, but specific clinical variables could not be recognized in these patients. The maximum intima-media thickness was significantly thinner in TGA (1.1 ± .7 mm) than in SVO (1.6 ± .9 mm; P = .001). The percentages of cases whose IJV flow reflux was increased by Valsalva maneuver showed no difference (P = .573) between TGA (26.0 %) and SVO (29.4%). MR diffusion-weighted imaging yielded small hyperintense signals in the hippocampus in 64 of 90 (71.1%) patients between 24 and 72 hours. Potential precipitating specific factors or events before the attacks could be recognized in 40 cases (24.2%) of 165 patients. Arterial ischemia and IJV flow reflux might not contribute to TGA pathophysiology. The vulnerability of the hippocampus to physical or emotional stress might be suspected as an underlying mechanism in some patients with TGA. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  17. Qualitative Analysis of the Resilience of Adult Japanese Patients with Type 1 Diabetes

    PubMed Central

    Nishio, Ikuko; Chujo, Masami

    2016-01-01

    Background Resilience strategies are what we use to avoid and recover from error. In this study, we used the grounded theory approach to evaluate the resilience of Japanese patients with Type 1 diabetes. Methods Semi-structured interviews were conducted with 15 adults with Type 1 diabetes. Then, using grounded theory, we created a new model of resilience in this population. Results The results suggested a core category, “to make progress along the resilience path,” comprising seven concepts classified into three stages. These seven concepts were as follows: “suffering from treatment,” “damaged trust as a person,” “persistence of afflictions,” “awareness of supporters,” “joy to be kept alive by insulin,” “actively seeking a future,” “being able to manage by oneself.” Individuals with Type 1 diabetes used difficult experiences to motivate their resilience and to improve their situation. Additionally, resilience was an important contributor to these individuals’ beliefs in their ability to face difficulties, to accept their illness and insulin therapy, and to control their illness. Resilience was also important to these individuals’ faith in the future and in medical care. Our results are applicable to clinical care and research, such as the development of preventive interventions aimed at building or strengthening protective skills related to diabetes and its management. Conclusion Ultimately, our goal is to equip adults with Type 1 diabetes with the tools to obtain sufficient behavioral and health-related resilience. Furthermore, these results highlight that maintaining resilience-related coping skills is important for adults and indicate that different psychological processes underlie resilience across the lifespan. PMID:27708534

  18. Mutation screen of GABRA1, GABRB2 and GABRG2 genes in Japanese patients with absence seizures.

    PubMed

    Ito, Minako; Ohmori, Iori; Nakahori, Tomoyuki; Ouchida, Mamoru; Ohtsuka, Yoko

    2005-08-05

    Absence seizures are classified into typical and atypical absences according to clinical and EEG characteristics. Although missense mutations in the GABA(A) receptor gamma2 subunits (GABRG2) gene have recently been detected in two families with typical absence seizures, no study has been carried out to clarify the relationship between atypical absence and GABA(A) receptors. We performed mutation analysis of all the coding exons of GABA(A) receptor alpha1, beta2 and gamma2 subunit (GABRA1, GABRB2 and GABRG2) genes by direct sequencing to clarify whether there was common molecular biological mechanism underlying both typical and atypical absences. We recruited 52 unrelated Japanese patients, thirty-eight with typical absences and 14 with atypical absences. They consisted of 38 with childhood absence epilepsy, three with Lennox-Gastaut syndrome, two with epilepsy with myoclonic-astatic seizures and nine with epilepsy with continuous spike-waves during slow wave sleep. All of the subjects were idiopathic or cryptogenic cases without any organic brain lesions or underlying diseases. We detected five polymorphisms (T156C in GABRA1, C1194T in GABRB2, and C315T, T588C and C1230T in GABRG2), and they are silent mutations. In conclusion, mutations in GABRA1, GABRB2 and GABRG2 do not seem to be a major genetic cause of epilepsy with typical and atypical absences in Japanese subjects.

  19. Longitudinal analysis of growth and body composition of Japanese 21-OHD patients in childhood.

    PubMed

    Matsubara, Yohei; Ono, Makoto; Miyai, Kentaro; Takizawa, Fumihiko; Takasawa, Kei; Onishi, Toshikazu; Kashimada, Kenichi; Mizutani, Shuki

    2013-01-01

    Substitution therapy of glucocorticoid is a major part of the treatment for 21-OHD (21-hydroxylase deficiency). However, the therapy causes two major adverse effects, impairment of linear growth and obesity, so that collecting precise growth data is essential for optimizing the therapy. We longitudinally evaluated the linear growth and the body composition of Japanese 21-OHD patients during childhood. For the present study, we chose 16 patients (eight of each sex) who were diagnosed during the newborn period, and continuously observed them in our institute until they were at least 15 years old. All patients were treated according to the guidelines from The Japanese Society for Pediatric Endocrinology. The final height standard deviation score (Ht-SDS) of all the patients was -1.18 ± 0.85 SD, and no significant differences were observed between males and females or between the simple virilizing form and the salt wasting form. As previously reported, in spite of nearly normal height at the onset of puberty, the pubertal height gains were severely impaired, resulting in reduced final heights. Body composition of the patients was evaluated with BMI-SDS. Our longitudinal data showed that BMI was increased up to +1.23 SD in males and up to +1.75 SD in females, and that adiposity rebound was precipitated. Our study should alert physicians to the risk of metabolic syndrome and provide a framework for further studies of metabolic syndrome in 21-OHD patients.

  20. Investigation of Risk Factors Affecting Lactate Levels in Japanese Patients Treated with Metformin.

    PubMed

    Yokoyama, Shota; Tsuji, Hideyuki; Hiraoka, Sachiko; Nishihara, Masayuki

    2016-01-01

    Metformin is a biguanaide antidiabetic drug used worldwide, and its effectiveness and benefits have already been established. However, the safety of high doses of metformin in Japanese patients, especially in elderly patients with a decreased renal function, remains unclear. Among the side effects of metformin, lactate acidosis is the most problematic due to a high mortality rate. Therefore, we assessed plasma lactate levels in metformin-treated patients to identify independent risk factors for hyperlactemia. 290 outpatients receiving various doses of metformin at our hospital were enrolled between March and July 2014. Serum electrolytes, Cre (creatinine), BUN (blood urea nitrogen), UA (uric acid), HbA1c (hemoglobin A1c), and lactate levels were investigated. Lactate levels did not significantly differ between the elderly (≥75 years) and non-elderly (<75 years) groups. Patients in the elderly group had a significantly lower daily metformin dose and estimated glomerular filtration rate (eGFR), compared with the non-elderly group (both p<0.005). Between with and without hyperlactemia groups, no significant differences were observed in either Cre or age. On the other hand, patients with hyperlactemia had a significantly higher dose of metformin than those without hyperlactemia (p<0.05). In this study, we found that old age and mildly impaired kidney function were not associated with increased lactate levels, and that a higher dose of metformin may be an independent risk factor for elevated lactate levels in Japanese patients.

  1. A phase I, pharmacokinetic and pharmacodynamic study of nimotuzumab in Japanese patients with advanced solid tumors.

    PubMed

    Okamoto, Wataru; Yoshino, Takayuki; Takahashi, Toshiaki; Okamoto, Isamu; Ueda, Shinya; Tsuya, Asuka; Boku, Narikazu; Nishio, Kazuto; Fukuoka, Masahiro; Yamamoto, Nobuyuki; Nakagawa, Kazuhiko

    2013-11-01

    Nimotuzumab is a humanized IgG₁ monoclonal antibody to the epidermal growth factor receptor (EGFR) and has demonstrated the absence of severe dermatological toxicity commonly caused by other EGFR-targeting antibodies. We conducted a phase I study to assess toxicities, pharmacokinetics, pharmacodynamics, and predictive biomarkers of nimotuzumab administered in Japanese patients with advanced solid tumors. Three dose levels, 100, 200, and 400 mg, of weekly i.v. nimotuzumab were given until disease progression or drug intolerability. Four patients with solid tumors were enrolled in each dose level. The expression and gene copy number of EGFR or its downstream transducers were investigated using skin biopsy samples and tumor specimens. Planned dose escalation was completed without dose-limiting toxicity, and maximum tolerated dose was not reached. No allergic reaction and hypomagnesaemia were observed, and grade 3 or 4 toxicity did not occur. The common toxicity was skin rash (58 %); however, all of them were grade 1 or 2. In skin biopsies, no correlation was shown between doses and the phosphorylation of EGFR or its downstream signal transducers. Of 11 evaluable patients, no objective response was obtained, while 8 patients had stable disease (73 %). Patients with a higher-EGFR gene copy number level measured by FISH showed a longer time to progression. Nimotuzumab administered weekly was feasible and well tolerated up to 400 mg in Japanese patients. A low dermatological toxicity could be a notable advantage as anti-EGFR mAb, and further evaluation is warranted.

  2. Tolerability and safety of classic cyclophosphamide, methotrexate, and fluorouracil treatment in Japanese patients with early breast cancer.

    PubMed

    Tada, Keiichiro; Ito, Yoshinori; Takahashi, Shunji; Iijima, Kohtaro; Miyagi, Yumi; Nishimura, Seiichiro; Takahashi, Kaoru; Makita, Masujiro; Iwase, Takuji; Yoshimoto, Masataka; Kasumi, Fujio

    2006-01-01

    Few reports have addressed the feasibility and safety of classic Cyclophosphamide, Methotrexate, and Fluorouracil (CMF) therapy in Japanese female breast cancer patients. Twenty-four Japanese patients who received classic CMF, identical to the originally described treatment regimen were studied in terms of treatment dose, treatment delay, and toxicity. Classic CMF was not discontinued in any of the cases. The median delay in treatment was 14 days, and the mean administered dose of cyclophosphamide was 98.2% of the planned dose. None of the patients suffered severe side-effects such as febrile neutropenia; however, in 22 patients in whom the effect of CMF on hair loss could be assessed, 7 (31.8%) had to wear hats or wigs. Classic CMF is a feasible and safe regimen in Japanese breast cancer patients. In Japan, this regimen is still available for some specific groups of early breast cancer patients.

  3. Traditional Japanese Kampo Medicine: Clinical Research between Modernity and Traditional Medicine—The State of Research and Methodological Suggestions for the Future

    PubMed Central

    Watanabe, Kenji; Matsuura, Keiko; Gao, Pengfei; Hottenbacher, Lydia; Tokunaga, Hideaki; Nishimura, Ko; Imazu, Yoshihiro; Reissenweber, Heidrun; Witt, Claudia M.

    2011-01-01

    The Japanese traditional herbal medicine, Kampo, has gradually reemerged and 148 different formulations (mainly herbal extracts) can be prescribed within the national health insurance system. The objective of this article is to introduce Kampo and to present information from previous clinical studies that tested Kampo formulae. In addition, suggestions on the design of future research will be stated. The literature search was based on a summary, up until January 2009, by the Japanese Society of Oriental Medicine and included only those trials which were also available in either Pubmed or ICHUSHI (Japan Medical Abstracts Society). We included 135 studies, half of these studies (n = 68) used a standard control and 28 a placebo control. Thirty-seven trials were published in English [all randomized controlled trials (RCTs)] and the remaining articles were in Japanese only. The sample size for most studies was small (two-third of the studies included less than 100 patients) and the overall methodological quality appeared to be low. None of the studies used Kampo diagnosis as the basis for the treatment. In order to evaluate Kampo as a whole treatment system, certain aspects should be taken into account while designing studies. RCTs are the appropriate study design to test efficacy or effectiveness; however, within the trial the treatment could be individualized according to the Kampo diagnosis. Kampo is a complex and individualized treatment with a long tradition, and it would be appropriate for further research on Kampo medicine to take this into account. PMID:21687585

  4. Cognitive behavioral therapy for depression in Japanese Parkinson’s disease patients: a pilot study

    PubMed Central

    Shinmei, Issei; Kobayashi, Kei; Oe, Yuki; Takagishi, Yuriko; Kanie, Ayako; Ito, Masaya; Takebayashi, Yoshitake; Murata, Miho; Horikoshi, Masaru; Dobkin, Roseanne D

    2016-01-01

    Objectives This study evaluated the feasibility of cognitive behavioral therapy (CBT) for Japanese Parkinson’s disease (PD) patients with depression. To increase cultural acceptability, we developed the CBT program using manga, a type of Japanese comic novel. Methods Participants included 19 non-demented PD patients who had depressive symptoms (GRID-Hamilton Rating Scale for Depression score ≥8). A CBT program comprising six sessions was individually administered. We evaluated the feasibility and safety of the CBT program in terms of the dropout rate and occurrence of adverse events. The primary outcome was depressive symptom reduction in the GRID-Hamilton Rating Scale for Depression upon completion of CBT. Secondary outcomes included changes in the self-report measures of depression (Beck Depression Inventory-II, Hospital Anxiety and Depression Scale-Depression), anxiety (Hospital Anxiety and Depression Scale-Anxiety, State and Trait Anxiety Inventory, Overall Anxiety Severity and Impairment Scale), functional impairment, and quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey). Results Of the 19 participants (mean age =63.8 years, standard deviation [SD] =9.9 years; mean Hohen–Yahr score =1.7, SD =0.8), one patient (5%) withdrew. No severe adverse event was observed. The patients reported significant improvements in depression (Hedges’ g =−1.02, 95% confidence interval =−1.62 to −0.39). The effects were maintained over a 3-month follow-up period. Most of the secondary outcome measurements showed a small-to-moderate but nonsignificant effect size from baseline to post-intervention. Conclusion This study provides preliminary evidence that CBT is feasible among Japanese PD patients with depression. Similar approaches may be effective for people with PD from other cultural backgrounds. The results warrant replication in a randomized controlled trial. PMID:27354802

  5. Serotonin 1A receptor gene is associated with Japanese methamphetamine-induced psychosis patients.

    PubMed

    Kishi, Taro; Tsunoka, Tomoko; Ikeda, Masashi; Kitajima, Tsuyoshi; Kawashima, Kunihiro; Okochi, Tomo; Okumura, Takenori; Yamanouchi, Yoshio; Kinoshita, Yoko; Ujike, Hiroshi; Inada, Toshiya; Yamada, Mitsuhiko; Uchimura, Naohisa; Sora, Ichiro; Iyo, Masaomi; Ozaki, Norio; Iwata, Nakao

    2010-02-01

    Several investigations have reported associations the serotonin 1A (5-HT1A) receptor to schizophrenia and psychotic disorders, making 5-HT1A receptor gene (HTR1A) an adequate candidate gene for the pathophysiology of schizophrenia and methamphetamine (METH)-induced psychosis. Huang and colleagues reported that rs6295 in HTR1A was associated with schizophrenia. The symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia. It may indicate that METH-induced psychosis and schizophrenia have common susceptibility genes. In support of this hypothesis, we reported that the V-act murine thymoma viral oncogene homologue 1 (AKT1) gene was associated with METH-induced psychosis and schizophrenia in the Japanese population. Furthermore, we conducted an analysis of the association of HTR1A with METH-induced psychosis. Using one functional SNP (rs6295) and one tagging SNP (rs878567), we conducted a genetic association analysis of case-control samples (197 METH-induced psychosis patients and 337 controls) in the Japanese population. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients. Rs878567 was associated with METH-induced psychosis patients in the allele/genotype-wise analysis. Moreover, this significance remained after Bonferroni correction. In addition, we detected an association between rs6295 and rs878567 in HTR1A and METH-induced psychosis patients in the haplotype-wise analysis. Although we detected an association between rs6295 and METH-induced psychosis patients, this significance disappeared after Bonferroni correction. HTR1A may play an important role in the pathophysiology of METH-induced psychosis in the Japanese population. However, because we did not perform a mutation scan of HTR1A, a replication study using a larger sample may be required for conclusive results. 2009. Published by Elsevier Ltd. All rights reserved.

  6. Psychological characteristics of Japanese patients with chronic pain assessed by the Rorschach test.

    PubMed

    Yamamoto, Kazumi; Kanbara, Kenji; Mutsuura, Hiromi; Ban, Ikumi; Mizuno, Yasuyuki; Abe, Tetsuya; Yoshino, Maki; Tajika, Aran; Nakai, Yoshihide; Fukunaga, Mikihiko

    2010-11-26

    The increasing number of patients with chronic pain in Japan has become a major issue in terms of the patient's quality of life, medical costs, and related social problems. Pain is a multi-dimensional experience with physiological, affective, cognitive, behavioral and social components, and recommended to be managed via a combination of bio-psycho-social aspects. However, a biomedical approach is still the dominant method of pain treatment in Japan. The current study aimed to evaluate comprehensive psychological functions and processes in Japanese chronic pain patients. The Rorschach Comprehensive System was administered to 49 in-patients with non-malignant chronic pain. Major variables and frequencies from the test were then compared to normative data from non-patient Japanese adults by way of the t-test and chi-square test. Patients exhibited high levels of emotional distress with a sense of helplessness with regard to situational stress, confusion, and ambivalent feelings. These emotions were managed by the patients in an inappropriate manner. Cognitive functions resulted in moderate dysfunction in all stages. Information processing tended to focus upon minute features in an inflexible manner. Mediational dysfunction was likely to occur with unstable affective conditions. Ideation was marked by pessimistic and less effective thinking. Since patients exhibited negative self-perception, their interpersonal relationship skills tended to be ineffective. Originally, our patients displayed average psychological resources for control, stress tolerance, and social skills for interpersonal relationships. However, patient coping styles were either situation- or emotion-dependent, and patients were more likely to exhibit emotional instability influenced by external stimuli, resulting in increased vulnerability to pain. Data gathered from the Rorschach test suggested psychological approaches to support chronic pain patients that are likely to be highly beneficial, and we

  7. Psychological characteristics of Japanese patients with chronic pain assessed by the Rorschach test

    PubMed Central

    2010-01-01

    Background The increasing number of patients with chronic pain in Japan has become a major issue in terms of the patient's quality of life, medical costs, and related social problems. Pain is a multi-dimensional experience with physiological, affective, cognitive, behavioral and social components, and recommended to be managed via a combination of bio-psycho-social aspects. However, a biomedical approach is still the dominant method of pain treatment in Japan. The current study aimed to evaluate comprehensive psychological functions and processes in Japanese chronic pain patients. Methods The Rorschach Comprehensive System was administered to 49 in-patients with non-malignant chronic pain. Major variables and frequencies from the test were then compared to normative data from non-patient Japanese adults by way of the t-test and chi-square test. Results Patients exhibited high levels of emotional distress with a sense of helplessness with regard to situational stress, confusion, and ambivalent feelings. These emotions were managed by the patients in an inappropriate manner. Cognitive functions resulted in moderate dysfunction in all stages. Information processing tended to focus upon minute features in an inflexible manner. Mediational dysfunction was likely to occur with unstable affective conditions. Ideation was marked by pessimistic and less effective thinking. Since patients exhibited negative self-perception, their interpersonal relationship skills tended to be ineffective. Originally, our patients displayed average psychological resources for control, stress tolerance, and social skills for interpersonal relationships. However, patient coping styles were either situation- or emotion-dependent, and patients were more likely to exhibit emotional instability influenced by external stimuli, resulting in increased vulnerability to pain. Conclusions Data gathered from the Rorschach test suggested psychological approaches to support chronic pain patients that are

  8. 2004 Japanese Society for Dialysis Therapy guidelines for renal anemia in chronic hemodialysis patients.

    PubMed

    Gejyo, Fumitake; Saito, Akira; Akizawa, Tadao; Akiba, Takashi; Sakai, Tatsuya; Suzuki, Masashi; Nishi, Shinichi; Tsubakihara, Yoshiharu; Hirakata, Hideki; Bessho, Masami

    2004-12-01

    The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Professor F. Gejyo of Niigata University, now publishes an original Japanese guideline entitled 'Guidelines for Renal Anemia in Chronic Hemodialysis Patients'. It includes the re-evaluation of the usage of recombinant human erythropoietin (rHuEPO) with the medical and economical arguments regarding the prognosis and the quality of life of Japanese hemodialysis patients. This guideline consists of 7 sections. The first section comprises the general definition and the differential diagnosis of anemia. The hemoglobin (Hb) level of the Japanese population seemed to be low when compared with that of the European and American populations. The second section describes the target Hb level in hemodialysis patients. Multivariate analysis of the data that were collected from dialysis institutions throughout the country showed that an Hb level of 10-11 g/dL (Ht level 30-33%) at the first dialysis session in a week is the ideal range for chronic hemodialysis patients in terms of the 3-5 year survival rate. The supine position at blood sampling and the sampling timing at the first dialysis session in a week might affect the lower setting of target Hb hematocrit (Ht), compared to that of European and American guidelines. However, we particularly recommended that an Hb level of 11-12 g/dL (Ht level from 33 to 36%) at the first dialysis session in a week is desirable in relatively young patients. In the third section, the markers of iron deficiency are discussed. The Transferin saturation test (TSAT) and serum ferritin were emphasized as the standard markers. The routes of administration of rHuEPO and its dosages are written in the fourth section. The subcutaneous route was associated with the occurrence of secondary red cell aplasia due to anti-rHuEPO antibodies; however, secondary red cell aplasia was seldom observed in the venous injection. From this fact we recommend venous injection for chronic

  9. Effect of lifestyle on asthma control in Japanese patients: importance of periodical exercise and raw vegetable diet.

    PubMed

    Iikura, Motoyasu; Yi, Siyan; Ichimura, Yasunori; Hori, Ai; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro; Mizoue, Tetsuya; Kobayashi, Nobuyuki

    2013-01-01

    The avoidance of inhaled allergens or tobacco smoke has been known to have favorable effects on asthma control. However, it remains unclear whether other lifestyle-related factors are also related to asthma control. Therefore, a comprehensive study to examine the associations between various lifestyle factors and asthma control was conducted in Japanese asthmatic patients. The study subjects included 437 stable asthmatic patients recruited from our outpatient clinic over a one-year period. A written, informed consent was obtained from each participant. Asthma control was assessed using the asthma control test (ACT), and a structured questionnaire was administered to obtain information regarding lifestyle factors, including tobacco smoking, alcohol drinking, physical exercise, and diet. Both bivariate and multivariate analyses were conducted. The proportions of total control (ACT = 25), well controlled (ACT = 20-24), and poorly controlled (ACT < 20) were 27.5%, 48.1%, and 24.5%, respectively. The proportions of patients in the asthma treatment steps as measured by Global Initiative for Asthma 2007 in step 1, step 2, step 3, step 4, and step 5 were 5.5%, 17.4%, 7.6%, 60.2%, and 9.4%, respectively. Body mass index, direct tobacco smoking status and alcohol drinking were not associated with asthma control. On the other hand, younger age (< 65 years old), passive smoking, periodical exercise (> 3 metabolic equivalents-h/week), and raw vegetable intake (> 5 units/week) were significantly associated with good asthma control by bivariate analysis. Younger age, periodical exercise, and raw vegetable intake were significantly associated with good asthma control by multiple linear regression analysis. Periodical exercise and raw vegetable intake are associated with good asthma control in Japanese patients.

  10. Effect of Lifestyle on Asthma Control in Japanese Patients: Importance of Periodical Exercise and Raw Vegetable Diet

    PubMed Central

    Iikura, Motoyasu; Yi, Siyan; Ichimura, Yasunori; Hori, Ai; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro; Mizoue, Tetsuya; Kobayashi, Nobuyuki

    2013-01-01

    Background The avoidance of inhaled allergens or tobacco smoke has been known to have favorable effects on asthma control. However, it remains unclear whether other lifestyle-related factors are also related to asthma control. Therefore, a comprehensive study to examine the associations between various lifestyle factors and asthma control was conducted in Japanese asthmatic patients. Methods The study subjects included 437 stable asthmatic patients recruited from our outpatient clinic over a one-year period. A written, informed consent was obtained from each participant. Asthma control was assessed using the asthma control test (ACT), and a structured questionnaire was administered to obtain information regarding lifestyle factors, including tobacco smoking, alcohol drinking, physical exercise, and diet. Both bivariate and multivariate analyses were conducted. Results The proportions of total control (ACT = 25), well controlled (ACT = 20-24), and poorly controlled (ACT < 20) were 27.5%, 48.1%, and 24.5%, respectively. The proportions of patients in the asthma treatment steps as measured by Global Initiative for Asthma 2007 in step 1, step 2, step 3, step 4, and step 5 were 5.5%, 17.4%, 7.6%, 60.2%, and 9.4%, respectively. Body mass index, direct tobacco smoking status and alcohol drinking were not associated with asthma control. On the other hand, younger age (< 65 years old), passive smoking, periodical exercise (> 3 metabolic equivalents-h/week), and raw vegetable intake (> 5 units/week) were significantly associated with good asthma control by bivariate analysis. Younger age, periodical exercise, and raw vegetable intake were significantly associated with good asthma control by multiple linear regression analysis. Conclusions Periodical exercise and raw vegetable intake are associated with good asthma control in Japanese patients. PMID:23874577

  11. Multiplex PCR for the Detection of 10 Viruses Causing Encephalitis/Encephalopathy and its Application to Clinical Samples Collected from Japanese Children with Suspected Viral.

    PubMed

    Pham, Ngan T K; Ushijima, Hiroshi; Thongprachum, Aksara; Trinh, Quang D; Khamrin, Pattara; Arakawa, Chikako; Ishii, Wakako; Okitsu, Shoko; Komine-Aizawa, Shihoko; Hayakawa, Satoshi

    2017-01-01

    Acute encephalitis is a serious neurological condition having a high mortality rate and affecting both children and adults. This study aimed to develop a multiplex PCR method for the simultaneous screening of clinical samples for the presence of the 10 viruses presently considered as the major viral causes of acute encephalitis/ encephalopathy in Asia. Using previously published primers that have been widely used to screen for herpes virus-6, influenza A virus, human parechovirus, herpes simplex viruses 1 and 2, Japanese encephalitis virus, group A rotavirus, enterovirus, adenovirus, and dengue virus in clinical samples, a single-tube multiplex PCR assay was developed and was tested for its sensitivity and specificity. The method was then applied to screen 57 clinical samples, consisting of 13 fecal samples, 5 throat swabs, 3 post-nasal swabs, 18 serum samples, and 18 cerebrospinal fluid (CSF) samples, collected from 18 hospitalized Japanese children with suspected viral encephalitis/encephalopathy for the target viruses, and the results were compared with those of a monoplex PCR method. Positive viral controls of the 10 viruses were correctly typed using this multiplex PCR method. The multiplex PCR method showed high specificity with no unspecific amplification to non-target viruses. The results of applying this PCR method for screening clinical samples showed that 6 fecal samples, 2 serum samples, and 1 CSF sample collected from 7 patients were positive for a virus, specifically group A rotavirus (4 patients, 22.2%), enterovirus (2 patients, 11.1%), or adenovirus (1 patient, 5.6%). In comparison with monoplex PCR, for group A rotavirus, enterovirus, and adenovirus, the sensitivity of this multiplex PCR method decreased for serum, cerebrospinal fluid, and throat swab samples. This newly developed multiplex PCR method is a simple, rapid diagnostic tool and can be used to screen clinical samples for viruses causing acute encephalitis/encephalopathy in children in

  12. Visual outcome in Japanese patients with Acanthamoeba keratitis.

    PubMed

    Yamazoe, K; Yamamoto, Y; Shimazaki-Den, S; Shimazaki, J

    2012-04-01

    To identify prognostic factors affecting visual outcome in Acanthamoeba keratitis (AK) treated with topical chlorhexidine gluconate (CHG). A total of 35 eyes in 34 patients with AK were treated with 0.02% topical CHG. Patients were divided into two groups according to the final visual outcome: Group 1, final visual acuity (VA) of 20/25 or greater (22 eyes); Group 2, less than 20/25 (13 eyes). We compared these groups and evaluated the effectiveness of topical CHG compared with outcomes in previous reports. Ring infiltrate was observed more often in Group 2 (4.5% vs 61.5%, OR 33.6, 95% confidence interval (CI) 3.4-333.9, P<0.01). The duration between onset and diagnosis of AK was significantly longer (24.9 days vs 48.4 days, OR 1.03, 95% CI 1.00-1.06, P = 0.04) and VA at initial examination (log MAR) significantly lower (0.47 vs 1.59, OR 25.5, 95% CI 3.4-186.7, P<0.01) in Group 2 (visual outcome <20/25). Multivariate analysis revealed that only VA at initial examination was independently associated with worse visual outcome (adjusted OR 24.5, 95% CI 1.9-312.6, P=0.01). Seventeen (85.0%) of the 20 eyes diagnosed within 1 month and 24 (82.8%) of 29 eyes diagnosed within 2 months achieved a VA of 20/40 or greater. VA at initial examination was the most predictive factors for final visual outcome in AK. Topical CHG was comparably effective to other treatments, including polyhexamethyl biguanide and propamidine isethionate.

  13. The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients.

    PubMed

    Kaihan, Ahmad Baseer; Yasuda, Yoshinari; Katsuno, Takayuki; Kato, Sawako; Imaizumi, Takahiro; Ozeki, Takaya; Hishida, Manabu; Nagata, Takanobu; Ando, Masahiko; Tsuboi, Naotake; Maruyama, Shoichi

    2017-03-27

    The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN). A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine. In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC. The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

  14. Dimensional analyses of frontal posed smile attractiveness in Japanese female patients.

    PubMed

    Hata, Kyoko; Arai, Kazuhito

    2016-01-01

    To identify appropriate dimensional items in objective diagnostic analysis for attractiveness of frontal posed smile in Japanese female patients by comparing with the result of human judgments. Photographs of frontal posed smiles of 100 Japanese females after orthodontic treatment were evaluated by 20 dental students (10 males and 10 females) using a visual analogue scale (VAS). The photographs were ranked based on the VAS evaluations and the 25 photographs with the highest evaluations were selected as group A, and the 25 photos with the lowest evaluations were designated group B. Then 12 dimensional items of objective analysis selected from a literature review were measured. Means and standard deviations for measurements of the dimensional items were compared between the groups using the unpaired t-test with a significance level of P < .05. Mean values were significantly smaller in group A than in group B for interlabial gap, intervermilion distance, maxillary gingival display, maximum incisor exposure, and lower lip to incisor (P < .05). Significant differences were observed only in the vertical dimension, not in the transverse dimension. Five of the 12 objective diagnostic items were correlated with human judgments of the attractiveness of frontal posed smile in Japanese females after orthodontic treatment.

  15. Pharmacokinetic-pharmacodynamic analysis of sunitinib-induced thrombocytopenia in Japanese patients with renal cell carcinoma.

    PubMed

    Nagata, Masashi; Ishiwata, Yasuyoshi; Takahashi, Yutaka; Takahashi, Hiromitsu; Saito, Kazutaka; Fujii, Yasuhisa; Kihara, Kazunori; Yasuhara, Masato

    2015-01-01

    The aim of the present study was to clarify the therapeutic range and adequate dose of sunitinib in Japanese renal cell carcinoma patients by means of a pharmacokinetic-pharmacodynamic analysis of sunitinib-induced thrombocytopenia. Six patients with renal cell carcinoma were enrolled in this study. After starting the sunitinib treatment, between three and seven blood samples were obtained from each patient just before the administration of sunitinib. Serum concentrations of sunitinib and its active metabolite N-desethyl-sunitinib were fit to the 1-compartment model with first-order absorption. Changes in platelet counts were fit to the pharmacokinetic-pharmacodynamic model, in which the proliferation of platelet progenitor cells was assumed to be linearly inhibited by sunitinib and its metabolite. All patients using 50 mg as an initial dose of sunitinib developed grade 2 or 3 thrombocytopenia. The pharmacokinetic-pharmacodynamic model created successfully described the time course of sunitinib-induced thrombocytopenia and could predict changes in platelet counts after alterations to the dosage of sunitinib administered. The simulation results indicated that the total trough level of sunitinib to avoid severe thrombocytopenia should be <100 ng/mL, and also that the initial daily dose of sunitinib could be reduced to 37.5 mg or 25 mg in most Japanese patients. In addition to the pharmacokinetic-guided dosage adjustment, the careful monitoring of platelet counts is required for the safe use of sunitinib.

  16. Impact of metabolic disturbances and malnutrition-inflammation on 6-year mortality in Japanese patients undergoing hemodialysis.

    PubMed

    Nakagawa, Naoki; Matsuki, Motoki; Yao, Naoyuki; Hirayama, Tomoya; Ishida, Hironori; Kikuchi, Kenjiro; Hasebe, Naoyuki

    2015-02-01

    Metabolic syndrome confers an increased risk of cardiovascular disease (CVD) in the general population. The relationship between adiponectins, and clinical outcomes in patients undergoing hemodialysis remains controversial. We investigated whether adiponectins, biomarkers of inflammation, nutrition status and clinical features predict the mortality of patients undergoing hemodialysis for 6 years. We measured baseline plasma total and high-molecular-weight (HMW) adiponectins, tumor necrosis factor (TNF)-α, serum high sensitivity C-reactive protein (hsCRP), and clinical characteristics including visceral fat area (VFA) and the Geriatric Nutritional Risk Index (GNRI) in 133 patients undergoing chronic hemodialysis. Forty-one of the 133 patients died during follow-up. The deceased patients were significantly older, had more prior CVD and diabetes, higher TNF-α and hsCRP levels but lower GNRI. VFA, and total and HMW adiponectin did not significantly differ between the two groups. TNF-α and hsCRP levels and GNRI score were significant for predicting all-cause and cardiovascular mortality in receiver operating curve analyses. When stratified by a GNRI score of 96, Cox proportional hazards analyses identified TNF-α as a significant predictor of all-cause mortality (hazard ratio [HR] 1.23; P = 0.038) and hsCRP as a significant predictor of all-cause and cardiovascular mortality (HR, 2.32, P = 0.003; HR 2.30, P = 0.012, respectively) after adjusting for age, sex, diabetes mellitus, and prior CVD, only in malnourished patients. These results demonstrate that malnutrition and the inflammatory markers TNF-α and hsCRP, but not metabolic markers, including VFA and adiponectins have a significant impact on 6-year all-cause and cardiovascular mortality in Japanese patients undergoing hemodialysis.

  17. Circulating transforming growth factor β-1 level in Japanese patients with Marfan syndrome.

    PubMed

    Ogawa, Naomi; Imai, Yasushi; Nishimura, Hiroshi; Kato, Masayoshi; Takeda, Norifumi; Nawata, Kan; Taketani, Tsuyoshi; Morota, Tetsuro; Takamoto, Shinichi; Nagai, Ryozo; Hirata, Yasunobu

    2013-01-01

    Marfan syndrome (MFS) is an inherited connective tissue disorder mainly caused by the fibrillin-1 mutation. Deficient fibrillin-1 is thought to result in the failed sequestration of transforming growth factor β (TGFβ) and subsequent activation of the TGFβ signaling pathway, suggesting that the circulating TGFβ level may be elevated in MFS, although its accurate measurement is complex due to ex vivo release from platelet stores upon platelet activation. We measured the plasma TGFβ1 levels of 32 Japanese MFS patients (22 medically untreated, 10 treated, 20 males, 30.1 ± 9.6 years old) and 30 healthy volunteers (19 males, 29.5 ± 5.8 years old) by ruthenium-based electrochemiluminescence platform (ECL). PF4 was also measured by enzyme immunoassay (EIA) as a platelet degranulation marker. There was no significant difference in the mean plasma TGFβ1 level between the MFS group (1.31 ± 0.40 ng/mL) and controls (1.17 ± 0.33 ng/mL) (P = 0.16, NS). Also, there was no significant difference between the untreated (1.24 ± 0.37 ng/mL) and treated (1.46 ± 0.45 ng/mL) MFS patients (P = 0.15, NS). We also measured PF4, which showed wide deviations but no significant difference between the two groups (P = 0.50). A difference in circulating TGFβ1 levels between MFS patients and controls was not detected in this Japanese population. Circulating TGFβ1 is not a diagnostic and therapeutic marker for Japanese MFS patients, although our findings do not eliminate the possible association of TGFβ with the pathogenesis of MFS.

  18. Is concomitant quadruple therapy for Helicobacter pylori eradication really needed for Japanese patients?

    PubMed Central

    Francesco, Vincenzo De; Zullo, Angelo; Hassan, Cesare

    2012-01-01

    The study found that the 7 d of concomitant therapy (lansoprazole, amoxicillin, clarithromycin and metronidazole) achieved significantly higher eradication rates compared to 7 d of triple therapy (lansoprazole, amoxicillin, clarithromycin), the intention to treat (ITT) cure rates being 94.9% and 68.3%, respectively. According to our opinion, this study is clinically relevant for Japanese physicians for at least 2 reasons: (1) the standard triple therapy (clarithromycin plus amoxicillin) achieved disappointing cure rates in Japan - in agreement with what was observed in several countries; and (2) the concomitant quadruple therapy is an effective therapeutic alternative. PMID:23494655

  19. Adherence and rehospitalizations in patients with schizophrenia: evidence from Japanese claims data

    PubMed Central

    Kuwabara, Hiroyo; Saito, Yoshimichi; Mahlich, Jörg

    2015-01-01

    Background The aim of this study is to analyze if there is a relationship between adherence to antipsychotic medication and rehospitalization for patients diagnosed with schizophrenia in Japan. Methods Based on Japanese claims data, we constructed three patient groups based on their medication possession ratio (MPR). Controlling for potential confounders, a Cox proportional hazard model was employed to assess if medication adherence affects the risk of rehospitalization. Results Patients with good adherence (MPRs from 0.8–1.1) had the lowest rates of admission. Both poor adherence (MPRs <0.8) and overadherence (MPRs >1.1) were associated with a significant higher risk of rehospitalization with hazard ratios of 4.7 and 2.0, respectively. Conclusion The results of this study support the notion that good adherence to antipsychotic medication reduces the risk of rehospitalization of schizophrenia patients. Appropriate measures should be taken to improve adherence of schizophrenia patients. PMID:25897229

  20. Elevated plasma homocysteine level is possibly associated with skin sclerosis in a series of Japanese patients with systemic sclerosis.

    PubMed

    Motegi, Sei-Ichiro; Toki, Sayaka; Yamada, Kazuya; Uchiyama, Akihiko; Ishikawa, Osamu

    2014-11-01

    Homocysteine is a sulfhydryl-containing amino acid that is derived from dietary methionine, and there has been increasing evidence that elevated plasma homocysteine levels are associated with increased risk of cardiovascular diseases, including carotid, coronary and peripheral arterial disease (PAD). The association of plasma homocysteine levels with peripheral vascular involvements, such as Raynaud phenomenon (RP), digital ulcers (DU) in systemic sclerosis (SSc) patients has not been well studied. The objective of this study was to examine plasma homocysteine levels and their clinical associations in patients with SSc. Plasma homocysteine levels in 151 Japanese patients with SSc and 20 healthy controls were examined. No significant differences were observed in plasma homocysteine levels between SSc patients and healthy individuals. Demographic and clinical features of the SSc patients revealed that severe skin sclerosis, anti-topoisomerase I antibody positivity, complications of DU, acro-osteolysis (AO) and interstitial lung disease (ILD) were significantly more prevalent among the patients with elevated plasma homocysteine levels. The plasma homocysteine levels were positively correlated with modified Rodnan total skin score. The plasma homocysteine levels in the SSc patients with DU, AO and ILD were significantly higher than those in the SSc without DU, AO and ILD, respectively. Plasma homocysteine levels did not correlate with either the mean or max intima-media thickness (IMT) or plaque score, suggesting that plasma homocysteine levels might not be associated with carotid artery atherosclerosis in SSc patients. The measurement of plasma homocysteine levels in SSc patients might be useful for the risk stratifications of severe skin sclerosis, DU and AO.

  1. The epidemiology, clinical features, and long-term prognosis of Japanese encephalitis in central sarawak, malaysia, 1997-2005.

    PubMed

    Ooi, Mong How; Lewthwaite, Penny; Lai, Boon Foo; Mohan, Anand; Clear, Daniela; Lim, Lina; Krishnan, Shekhar; Preston, Teresa; Chieng, Chae Hee; Tio, Phaik Hooi; Wong, See Chang; Cardosa, Jane; Solomon, Tom

    2008-08-15

    Japanese encephalitis is a major public health problem in Asia. However, there is little data on the long-term outcome of Japanese encephalitis survivors. We prospectively evaluated children with serologically confirmed Japanese encephalitis over an 8.3-year period. The patients were assessed and their outcomes were graded with a functional outcome score at hospital discharge and at follow-up appointments. We examined how patient outcome at hospital discharge compared with that at long-term follow-up visits, when changes in outcome occurred, and the prognostic indicators of the eventual outcome. One hundred and eighteen patients were recruited into the study, and 10 (8%) died during the acute phase of illness. At hospital discharge, 44 (41%) of the 108 patients who survived had apparent full recovery; 3 (3%) had mild, 28 (26%) had moderate, and 33 (31%) had severe neurological sequelae. Eighty six of the 108 patients were followed up for a median duration of 52.9 months (range, 0.9-114.9 months). During follow-up, 31 patients experienced improvement, but 15 patients experienced deterioration in their outcome grade. In most cases, assessment during the first 3-6 months after hospital discharge was predictive of the long-term outcome. More than one-half of the patients continued to experience neuropsychological sequelae and behavioral disorders. A combination of poor perfusion, Glasgow coma score < or =8, and > or =2 witnessed seizures predicted a poor long-term outcome with 65% sensitivity and 92% specificity. Neurological assessment of Japanese encephalitis survivors at hospital discharge does not predict long-term outcome. Seizures and shock are treatable risk factors for a poor outcome at hospital discharge and at long-term follow-up visits.

  2. Relationships between serum irisin levels and metabolic parameters in Japanese patients with obesity

    PubMed Central

    Kurose, Satoshi; Shinno, Hiromi; Cao Thi Thu, Ha; Tamanoi, Atsuko; Tsutsumi, Hiromi; Hasegawa, Takaaki; Nakajima, Toshiaki; Kimura, Yutaka

    2016-01-01

    Summary Background/Purpose Irisin is a skeletal muscle myokine that causes the brown coloration of white fat, promotes fat burning, inhibits weight gain and may be useful for treatment of obesity. Irisin is also related to glucose/lipid metabolism and may prevent onset of diabetes, but a consensus on irisin secretion has not been reached. The purpose of this study was to determine the relationships between serum irisin levels and physical factors in untreated Japanese men and women with obesity. Methods The subjects were 66 untreated patients with obesity (body mass index ≥30 kg m−2) who visited our obesity clinic. The subjects included 19 men and 47 women with a mean age of 45.7 ± 13.4 years, mean body weight of 93.8 ± 17.6 kg, and mean body mass index of 36.5 ± 4.7 kg m−2. At the initial visit, blood sampling was performed, body composition was evaluated using dual energy X‐ray absorptiometry, and exercise tolerance was determined in a cardiopulmonary exercise test. Homeostasis model of assessment – insulin resistance (HOMA‐IR), an index of insulin resistance, and the serum level of irisin were measured. Results In men, serum irisin was positively correlated with fasting blood glucose (r = 0.491, P < 0.05), immunoreactive insulin (r = 0.536, P < 0.05), HOMA‐IR (r = 0.635, P < 0.01), body weight (r = 0.491, P < 0.05), lean body mass of the trunk (r = 0.579, P < 0.05) and whole lean body mass (r = 0.489, P < 0.05). In women, serum irisin was positively correlated with immunoreactive insulin (r = 0.502, P < 0.01) and HOMA‐IR (r = 0.385, P < 0.01). In both sexes, HOMA‐IR was an independent variable associated with obesity (men: β = 0.635, R2 = 0.369, P < 0.01; women: β = 0.385, R2 = 0.129, P < 0.01). Conclusion The serum level of irisin was positively correlated with HOMA‐IR in Japanese patients with obesity of both sexes. This

  3. Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome.

    PubMed

    Tanioka, Miki; Takahashi, Katsu; Kawabata, Tomohiro; Kosugi, Shinji; Murakami, Kenichiro; Miyachi, Yoshiki; Nishigori, Chikako; Iizuka, Tadahiko

    2005-01-01

    We identified seven novel germline mutations of the PTCH gene in eight unrelated Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to ensure genetic diagnosis, all 23 coding exons of the PTCH gene were amplified from genomic DNA by polymerase chain reaction (PCR) and sequenced. Mutations were found in all eight patients with NBCCS. The mutations detected in this study include one insertion/deletion mutation, one 1-bp insertion, two 1-bp deletions, one nonsense mutation and two missense mutations. None of the mutations have been previously reported. Five mutations caused premature stop codons that are predicted to result in a truncated protein. In the two missense mutations, the strong basic residue arginine was substituted by serine or glycine in highly conserved components of the putative transmembrane domain of PTCH, and these mutations may therefore affect the conformation and function of the PTCH protein. No phenotype-genotype relationships were found in the Japanese NBCCS patients, consistent with results of previous studies on NBCCS in African-American and Caucasian patients.

  4. Effect of azilsartan versus candesartan on nocturnal blood pressure variation in Japanese patients with essential hypertension.

    PubMed

    Rakugi, Hiromi; Kario, Kazuomi; Enya, Kazuaki; Igeta, Masataka; Ikeda, Yoshinori

    2013-09-01

    Abnormal variations in night-time hypertension such as "non-dipping" type (< 10% decrease in nocturnal systolic blood pressure [SBP] from daytime SBP) are a risk factor for cardiovascular events independent of 24-h BP. As part of a randomized, double-blind study of azilsartan (20-40 mg once daily) and candesartan (8-12 mg once daily) in Japanese patients with essential hypertension, an exploratory analysis was performed using ambulatory BP monitoring (ABPM) at baseline and Week 14. Effects of study drugs on nocturnal BP variations according to patients' nocturnal SBP dipping status were evaluated. ABPM data were available for 273 patients treated with azilsartan and 275 with candesartan. In the dipping group (≥ 10% decrease from daytime SBP), azilsartan produced a greater reduction from baseline in daytime than in night-time SBP (- 14.1 and - 10.9 mmHg, respectively), and the change in daytime SBP was significantly greater with azilsartan than with candesartan (p = 0.0077). In the non-dipping group, azilsartan produced a greater reduction from baseline in night-time than in daytime SBP (- 20.2 and - 9.9 mmHg, respectively), and reductions in both night-time SBP (p = 0.02) and daytime SBP (p = 0.0042) were significantly greater with azilsartan than with candesartan. Once-daily azilsartan improved non-dipping night-time SBP to a greater extent than candesartan in Japanese patients with grade I-II essential hypertension.

  5. Assessment of Japanese stimulant control law offenders using the Addiction Severity Index--Japanese version: comparison with patients in treatment settings.

    PubMed

    Watanabe, Takashi; Ogai, Yasukazu; Koga, Takehiro; Senoo, Eiichi; Nakamura, Kazuhiko; Mori, Norio; Ikeda, Kazutaka

    2009-12-01

    The present study assessed problems in Japanese prisoners (inmates) who abused methamphetamine. Fifty-two male inmates were assessed in 2005-2007 using the Addiction Severity Index-Japanese version and compared with 55 male methamphetamine abusers in hospitals and recovery centers. The chi(2) and Mann-Whitney-Wilcoxon tests showed that the inmates had a significantly lower education level, more frequently had full-time jobs, had more experience living with a sexual partner, and more frequently had a history of juvenile delinquency and criminal records than patients. Although psychiatric symptoms, such as depression, anxiety, and hallucinations, were not common among inmates, suicidal behavior and trouble controlling violence were common in both groups.

  6. A novel frameshift mutation of DDHD1 in a Japanese patient with autosomal recessive spastic paraplegia.

    PubMed

    Miura, Shiroh; Morikawa, Takuya; Fujioka, Ryuta; Kosaka, Kengo; Yamada, Kohei; Hattori, Gohsuke; Motomura, Manabu; Taniwaki, Takayuki; Shibata, Hiroki

    2016-08-01

    Spastic paraplegia (SPG) type 28 is an autosomal recessive SPG caused by mutations in the DDHD1 gene. We examined a Japanese 54-years-old male patient with autosomal recessive SPG. His parents were consanguineous. He needed a wheelchair for transfer due to spastic paraplegia. There was a history of operations for bilateral hallux valgus, thoracic ossification of the yellow ligament, bilateral carpal tunnel syndrome, bilateral ankle contracture, and lumbar spinal canal stenosis. He noticed gait disturbance at age 14. He used a cane for walking in his 40s. On neurological examination, he showed hyperreflexia, spasticity, and weakness in the lower extremities and bilateral Babinski reflexes. Urinary dysfunctions and impaired vibration sense in the lower limbs were observed. By exome sequencing analysis using Agilent SureSelect and Illumina MiSeq, we identified 17,248 homozygous nucleotide variants in the patient. Through the examination of 48 candidate genes known to be responsible for autosomal recessive SPG, we identified a novel homozygous 4-bp deletion, c.914_917delGTAA, p.Ser305Ilefs*2 in exon2 of the DDHD1 gene encoding phosphatidic acid-preferring phospholipase A1 (PA-PLA1). The mutation is expected to cause a frameshift generating a premature stop codon 3-bp downstream from the deletion. In consequence, the DDHD domain that is known to be critical for PLA1 activity is completely depleted in the mutated DDHD1 protein, predicted to be a functionally null mutation of the DDHD1 gene. By Sanger sequencing, we confirmed that both parents are heterozygous for the mutation. This variation was not detected in 474 Japanese control subjects as well as the data of the 1,000G Project. We conclude that the novel mutation in DDHD1 is the causative variant for the SPG28 patient that is the first record of the disease in Japanese population.

  7. Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia

    SciTech Connect

    Kobayashi, Keiko; Shaheen, Nazma; Terazono, Hiroki; Saheki, Takeyori

    1994-12-01

    Citrullinemia is an autosomal recessive disease caused by a genetic deficiency of argininosuccinate synthetase. In order to characterize mutations in Japanese patients with classical citrullinemia, RNA isolated from 10 unrelated patients was reverse-transcribed, and cDNA amplified by PCR was cloned and sequenced. The 10 mutations identified included 6 missense mutations (A118T, A192V, R272C, G280R, R304W, and R363L), 2 mutations associated with an absence of an exon 7 or exon 13, 1 mutation with a deletion of the first 7 bp in exon 16 (which might be caused by abnormal splicing), and 1 mutation with an insertion of 37 bp within exons 15 and 16 in cDNA. The insertion mutation and the five missense mutations (R304W being excluded) are new mutations described in the present paper. These are in addition to 14 mutations (9 missense mutations, 4 mutations associated with an absence of an exon in mRNA, and 1 splicing mutation) that we identified previously in mainly American patients with neonatal citrullinemia. Two of these 20 mutations, a deletion of exon 13 sequence and a 7-bp deletion in exon 16, were common to Japanese and American populations from different ethnic backgrounds; however, other mutations were unique to each population. Furthermore, the presence of a frequent mutation - the exon 7 deletion mutation in mRNA, which accounts for 10 of 23 affected alleles - was demonstrated in Japanese citrullinemia. This differs from the situation in the United States, where there was far greater heterogeneity of mutations.

  8. Nurse awareness of clinical research: a survey in a Japanese University Hospital

    PubMed Central

    2014-01-01

    Background Clinical research plays an important role in establishing new treatments and improving the quality of medical practice. Since the introduction of the concept of clinical research coordinators (CRC) in Japan, investigators and CRC work as a clinical research team that coordinates with other professionals in clinical trials leading to drug approval (registration trials). Although clinical nurses collaborate with clinical research teams, extended clinical research teams that include clinical nurses may contribute to the ethical and scientific pursuit of clinical research. Methods As knowledge of clinical research is essential for establishing an extended clinical research team, we used questionnaires to survey the knowledge of clinical nurses at Tokushima University Hospital. Five-point and two-point scales were used. Questions as for various experiences were also included and the relationship between awareness and experiences were analyzed. Results Among the 597 nurses at Tokushima University Hospital, 453 (75.9%) responded to the questionnaires. In Japan, registration trials are regulated by pharmaceutical affairs laws, whereas other types of investigator-initiated research (clinical research) are conducted based on ethical guidelines outlined by the ministries of Japan. Approximately 90% of respondents were aware of registration trials and clinical research, but less than 40% of the nurses were aware of their difference. In clinical research terminology, most respondents were aware of informed consent and related issues, but ≤50% were aware of other things, such as the Declaration of Helsinki, ethical guidelines, Good Clinical Practice, institutional review boards, and ethics committees. We found no specific tendency in the relationship between awareness and past experiences, such as nursing patients who were participating in registration trials and/or clinical research or taking a part in research involving patients as a nursing student or a nurse

  9. Failure of mefloquine therapy in progressive multifocal leukoencephalopathy: report of two Japanese patients without human immunodeficiency virus infection.

    PubMed

    Kobayashi, Zen; Akaza, Miho; Numasawa, Yoshiyuki; Ishihara, Shoichiro; Tomimitsu, Hiroyuki; Nakamichi, Kazuo; Saijo, Masayuki; Morio, Tomohiro; Shimizu, Norio; Sanjo, Nobuo; Shintani, Shuzo; Mizusawa, Hidehiro

    2013-01-15

    Although progressive multifocal leukoencephalopathy (PML) cases showing responses to mefloquine therapy have been reported, the efficacy of mefloquine for PML remains unclear. We report on the failure of mefloquine therapy in two Japanese patients with PML unrelated to human immunodeficiency virus. One of the patients was a 47-year-old male who had been treated with chemotherapy for Waldenström macroglobulinemia, and the other was an 81-year-old male with idiopathic CD4(+) lymphocytopenia. Diagnosis of PML was established based on MRI findings and increased JC virus DNA in the cerebrospinal fluid in both patients. Mefloquine was initiated about 5 months and 2 months after the onset of PML, respectively. During mefloquine therapy, clinical and radiological progression was observed, and JC virus DNA in the cerebrospinal fluid was increased in both patients. Both patients died about 4 months and 2 months after initiation of mefloquine, respectively. Further studies are necessary to clarify the differences between mefloquine responders and non-responders in PML.

  10. Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041).

    PubMed

    Yamazaki, Naoya; Takenouchi, Tatsuya; Fujimoto, Manabu; Ihn, Hironobu; Uchi, Hiroshi; Inozume, Takashi; Kiyohara, Yoshio; Uhara, Hisashi; Nakagawa, Kazuhiko; Furukawa, Hiroshi; Wada, Hidefumi; Noguchi, Kazuo; Shimamoto, Takashi; Yokota, Kenji

    2017-04-01

    This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma. Pembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review. Forty-two patients with advanced melanoma received pembrolizumab. A primary cutaneous histology was observed in 34 patients (81.0%), while a primary mucosal histology was observed in 8 patients (19.0%). Thirty-four patients (81.0%) experienced treatment-related adverse events (AEs). The most common treatment-related AEs were pruritus, maculopapular rash, malaise, and hypothyroidism. Grade 3-5 treatment-related AEs occurred in 8 patients (19.0%). The only grade 3-5 treatment-related AE reported in at least two patients was anemia. There were two treatment-related deaths (unknown cause and cerebral hemorrhage). Among the 37 evaluable patients, the confirmed overall response rates (ORRs) determined by central review were 24.1% (95% CI 10.3-43.5) for cutaneous melanoma and 25.0% (95% CI 3.2-65.1) for mucosal melanoma. The responses were durable, and the median duration of response was not reached in either population. The median overall survival (OS) was not reached, with a 12-month OS of 82.7% for cutaneous melanoma and 51.4% for mucosal melanoma. The safety profile of pembrolizumab in Japanese patients was similar to that reported in the previous clinical studies. Pembrolizumab provided promising anti-tumor activity in Japanese patients with advanced melanoma.

  11. Cognitive Dysfunction Survey of the Japanese Patients with Moyamoya Disease (COSMO-JAPAN Study): Study Protocol

    PubMed Central

    TAKAGI, Yasushi; MIYAMOTO, Susumu

    2015-01-01

    Moyamoya disease is a cerebrovascular occlusive disease characterized by progressive stenosis or by occlusion at the terminal portion of the bilateral internal carotid arteries. The unusual vascular network (moyamoya vessels) at the base of the brain with this disease as collateral channels is developed in this disease. Social independence because of cognitive impairment has recently been recognized as an important unsolved social issue with adult moyamoya disease. The patients with cognitive impairment have difficulty in proving their status because the standard neuroradiological and neuropsychological methods to define cognitive impairment with moyamoya disease are not determined. These patients with cognitive impairment should be supported by social welfare as psychologically handicapped persons. Thus Cognitive Dysfunction Survey of the Japanese Patients with Moyamoya Disease (COSMO-JAPAN study) is planned. In this study, we want to establish a standard finding of the cognitive impairment in patients with moyamoya disease. PMID:25739435

  12. Cognitive Dysfunction Survey of the Japanese Patients with Moyamoya Disease (COSMO-JAPAN Study): study protocol.

    PubMed

    Takagi, Yasushi; Miyamoto, Susumu

    2015-01-01

    Moyamoya disease is a cerebrovascular occlusive disease characterized by progressive stenosis or by occlusion at the terminal portion of the bilateral internal carotid arteries. The unusual vascular network (moyamoya vessels) at the base of the brain with this disease as collateral channels is developed in this disease. Social independence because of cognitive impairment has recently been recognized as an important unsolved social issue with adult moyamoya disease. The patients with cognitive impairment have difficulty in proving their status because the standard neuroradiological and neuropsychological methods to define cognitive impairment with moyamoya disease are not determined. These patients with cognitive impairment should be supported by social welfare as psychologically handicapped persons. Thus Cognitive Dysfunction Survey of the Japanese Patients with Moyamoya Disease (COSMO-JAPAN study) is planned. In this study, we want to establish a standard finding of the cognitive impairment in patients with moyamoya disease.

  13. Quality of life in Japanese female patients with systemic lupus erythematosus: Evaluation using the Short Form 36 Health Survey.

    PubMed

    Furukawa, Makio; Kiyohara, Chikako; Horiuchi, Takahiko; Tsukamoto, Hiroshi; Mitoma, Hiroki; Kimoto, Yasutaka; Uchino, Ayumi; Nakagawa, Misato; Oryoji, Kensuke; Shimoda, Terufumi; Akashi, Koichi

    2016-01-01

    Aspects of health-related quality of life (HRQoL) are important for assessing perceived health status and treatment burden. We evaluated HRQoL using Short Form 36 Health Survey (SF-36) and factors associated with HRQoL. We collected basic and lifestyle-related, clinical, and treatment characteristics among 119 female Japanese patients with systemic lupus erythematosus (SLE). Odds ratios (ORs) and their 95% confidence intervals were assessed for associations between HRQoL and selected factors. Irregularity of sleep was significantly associated with risk of lower role physical (RP) (OR = 8.27), vitality (VT) (OR = 8.45), and role emotional (OR = 10.7) domains. Compared with clerical work, non-clerical work was significantly associated with risk of lower RP (OR = 7.39), and unemployment was significantly associated with risk of lower VT (OR = 41.0). Daily soybean intake was associated with improved General Health or GH (OR = 0.17). Compared with Systemic Lupus Collaborative Clinics Damage Index (SDI) = 0, SDI > 2 was associated with risk of lower PF (OR = 7.88), RP (OR = 4.29), and bodily pain (OR = 3.06) domains. Reduced HRQoL was observed in our SLE patients. Interventions addressing sleep and work disturbances, as well as daily soybean consumption, could alter the HRQoL of SLE patients.

  14. Anakinra improves sensory deafness in a Japanese patient with Muckle-Wells syndrome, possibly by inhibiting the cryopyrin inflammasome.

    PubMed

    Yamazaki, Takashi; Masumoto, Junya; Agematsu, Kazunaga; Sawai, Nobukuni; Kobayashi, Shinji; Shigemura, Tomonari; Yasui, Kozo; Koike, Kenichi

    2008-03-01

    Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory syndrome. Patients with MWS have a mutation in CIAS1, the gene encoding cryopyrin, a component of the inflammasome that regulates the processing of interleukin-1beta (IL-1beta). In this report we describe an 8-year-old Japanese girl with MWS who had symptoms of periodic fever, urticarial rash, conjunctivitis, arthropathy, and sensory deafness. Laboratory analysis of the patient's serum showed abnormally high concentrations of C-reactive protein, serum amyloid A, and IL-1beta, and she had a heterozygous mutation in the CIAS1 gene, with C-to-T transversion at nucleotide position 778, encoding an arginine-to-tryptophan mutation at position 260 (R260W). Mononuclear cells (MNCs) isolated from the patient secreted large amounts of IL-1beta, without stimulation, and were highly sensitive to muramyldipeptide and lipopolysaccharide. After treatment with anakinra, laboratory results normalized, and clinical symptoms, including sensory deafness, disappeared, while MNCs appeared to remain activated. Thus, our case suggests that anakinra possibly affects the cryopyrin inflammasome and markedly improves the clinical and laboratory manifestations of MWS.

  15. Validity, reliability, and assessment sensitivity of the Japanese version of the short-form McGill pain questionnaire 2 in Japanese patients with neuropathic and non-neuropathic pain.

    PubMed

    Maruo, Tomoyuki; Nakae, Aya; Maeda, Lynn; Shi, Kenrin; Takahashi, Kayoko; Morris, Shayne; Hosomi, Koichi; Kanatani, Hiroshi; Matsuzaki, Taiga; Saitoh, Youichi

    2014-11-01

    The objective of this study was to define the validity, reliability, and assessment sensitivity of the Japanese version of the Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2-J). This is a cross-sectional study. The original SF-MPQ-2 was translated into Japanese to create the SF-MPQ-2-J, and the cross-cultural equivalence of assessment tool for Japanese patients was validated. The reliability of the SF-MPQ-2-J was assessed using internal consistency, reliability coefficients (Cronbach's α), and reproducibility coefficients (intraclass correlation coefficient) obtained using 234 patients with chronic pain. SF-MPQ-2-J validity was assessed based on associations identified between total and subscale scores compared with other assessment methods. A confirmatory factor analysis (CFA) was also performed to test the theoretical structure of the SF-MPQ-2-J. The internal consistencies calculated included continuous pain, α=0.893; intermittent pain, α=0.875; predominantly neuropathic pain, α=0.917; affective descriptors, α=0.857; and total score, α=0.907. The reproducibility coefficients calculated included continuous pain, ρ=0.81; intermittent pain, ρ=0.78; predominantly neuropathic pain, ρ=0.85; affective descriptors, ρ=0.75; and total score, ρ=0.83. The CFA showed that the model fit of the readily interpretable subscales was acceptable, and the goodness of fit index value was 0.917. In addition, the mean predominantly neuropathic pain subscale score was found to be significantly higher for patients with neuropathic pain vs non-neuropathic pain. These findings suggest that the reliability and validity of the SF-MPQ-2-J are excellent, and the SF-MPQ-2-J represents a cross-cultural equivalent to SF-MPQ-2. Consequently, the latter is suitable for research and clinical use, and for discriminating neuropathic pain from non-neuropathic pain. Wiley Periodicals, Inc.

  16. Recent Clinical Characteristics of Labors Using Three Japanese Systems of Midwife-Led Primary Delivery Care

    PubMed Central

    Suzuki, Shunji

    2016-01-01

    Objective. The objective of this study was to describe the recent clinical characteristics of labor using 3 systems of Japanese midwife-led primary delivery care, as follows: (1) those intending to give birth at home managed by midwives who do not belong to our hospital, (2) those planning to give birth in our hospital managed by the same midwives, and (3) those planning to give birth managed by midwives who belong to our hospital. Methods. A retrospective cohort study was performed. Results. There were no significant differences in the obstetric or neonatal outcomes among the 3 groups. The rate of transfers during labor with the system involving midwives belonging to our hospital was higher than those with the other 2 systems. In addition, the timing of transfers in the system with the midwives belonging to our hospital was earlier than with the other 2 systems. Among the 3 groups, there were no significant differences in the rate of the main 2 indications for transfers: fetal heart rate abnormality and failure to progress. Conclusion. There were no significant differences in perinatal outcomes among the 3 systems; however, there were some differences in the status of transfers to obstetric shared care. PMID:27034827

  17. Indications, applications, and outcomes of inferior vena cava filters for venous thromboembolism in Japanese patients.

    PubMed

    Yamashita, Yugo; Unoki, Takashi; Takagi, Daisuke; Hamatani, Yasuhiro; Ishii, Mitsuru; Iguchi, Moritake; Ogawa, Hisashi; Masunaga, Nobutoyo; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru; Akao, Masaharu

    2016-07-01

    A recent multicenter registry study of venous thromboembolism (VTE) patients in Japan demonstrated a high prevalence of inferior vena cava (IVC) filter placement. However, data regarding indications, applications, and outcomes of IVC filters in Japanese patients are quite limited. This study was an observational, single-center, retrospective cohort study of all consecutive patients with acute VTE treated between March 2006 and February 2014. Data extracted included patient demographics, indications, applications, and complications of IVC filters, as well as VTE recurrence and death. A total of 257 consecutive patients were analyzed. Seventy-eight patients (30 %) received IVC filters. The proportions of IVC filter placement were 26 % for deep-vein thrombosis (DVT) alone, 10 % for pulmonary embolism (PE) alone, and 46 % for both DVT and PE. There was no significant difference in patient demographics between the IVC filter group and no-IVC filter group. Stated indications for filter placement were 24 cases (30 %) of DVT in intrapelvic veins, 16 cases (20 %) of DVT in proximal veins, and 11 cases (14 %) of contraindication to anticoagulant therapy. In the IVC filter group, cases of class I indication (guidelines: JCS 75:1258-1281, 2009) numbered only 6 (8 %). Many of the retrievable IVC filters were not removed and placed permanently and the retrieval rate was 42 %. We found complications of IVC filters in 8 cases (10 %). IVC filter placement was significantly associated with a better survival rate and a higher incidence of DVT recurrence during a mean observation period of 541 days. Our research suggests the frequent use of IVC filters for VTE treatment, combined with a low retrieval rate. Most of the stated indications of IVC filter placement for VTE in Japanese patients were cases of DVT in intrapelvic veins or proximal veins, not cases of contraindication to anticoagulant therapy.

  18. Effects of liraglutide on postprandial insulin and glucagon responses in Japanese patients with type 2 diabetes

    PubMed Central

    Matsumoto, Shinobu; Yamazaki, Masahiro; Kadono, Mayuko; Iwase, Hiroya; Kobayashi, Kanae; Okada, Hiroshi; Fukui, Michiaki; Hasegawa, Goji; Nakamura, Naoto

    2013-01-01

    This study assessed the endocrine pancreatic responses to liraglutide (0.9 mg once a day) during normal living conditions in Japanese patients with type 2 diabetes. The study included 14 hospitalized patients with type 2 diabetes. Meal tests were performed after improvement of glycemic control achieved by two weeks of multiple insulin injection therapy and after approximately two weeks of liraglutide treatment. Continuous glucose monitoring was performed to compare daily variation in glycemic control between multiple insulin injection therapy and liraglutide treatment. Liraglutide reduced plasma glucose levels after the test meals (60–180 min; p<0.05), as a result of significant increases in insulin secretion (0–180 min; p<0.05) and decreases in the incremental ratio of plasma glucagon (15–60 min; p<0.05). Continuous glucose monitoring showed that liraglutide treatment was also associated with a decrease in glucose variability. We also demonstrated that optimal glycemic control seen as a reduction in 24-h mean glucose levels and variability was obtained only with liraglutide monotherapy. In conclusion, liraglutide treatment increases insulin secretion and suppresses glucagon secretion in Japanese patients with type 2 diabetes under normal living conditions. The main therapeutic advantages of liraglutide are its use as monotherapy and its ability to decrease glucose variability. PMID:23874074

  19. Are cam and pincer deformities as common as dysplasia in Japanese patients with hip pain?

    PubMed

    Mori, R; Yasunaga, Y; Yamasaki, T; Nakashiro, J; Fujii, J; Terayama, H; Ohshima, S; Ochi, M

    2014-02-01

    In Japan, osteoarthritis (OA) of the hip secondary to acetabular dysplasia is very common, and there are few data concerning the pathogeneses and incidence of femoroacetabular impingement (FAI). We have attempted to clarify the radiological prevalence of painful FAI in a cohort of Japanese patients and to investigate the radiological findings. We identified 176 symptomatic patients (202 hips) with Tönnis grade 0 or 1 osteoarthritis, whom we prospectively studied between August 2011 and July 2012. There were 61 men (65 hips) and 115 women (137 hips) with a mean age of 51.8 years (11 to 83). Radiological analyses included the α-angle, centre-edge angle, cross-over sign, pistol grip deformity and femoral head neck ratio. Of the 202 hips, 79 (39.1%) had acetabular dysplasia, while 80 hips (39.6%) had no known aetiology. We found evidence of FAI in 60 hips (29.7%). Radiological FAI findings associated with cam deformity were the most common. There was a significant relationship between the pistol grip deformity and both the α-angle (p < 0.001) and femoral head-neck ratio (p = 0.024). Radiological evidence of symptomatic FAI was not uncommon in these Japanese patients.

  20. Variations in the core promoter/pre-core region in HBV genotype C in Japanese and Northern Vietnamese patients.

    PubMed

    Truong, Bui Xuan; Yano, Yoshihiko; Seo, Yasushi; Phuong, Tran Minh; Tanaka, Yasuhito; Kato, Hirotaka; Miki, Akira; Utsumi, Takako; Azuma, Takeshi; Trach, Nguyen Khanh; Mizokami, Masashi; Hayashi, Yoshitake; Kasuga, Masato

    2007-09-01

    Hepatitis B virus (HBV) subgenotypes Cs (C1) and Ce (C2) are common in East Asia. To investigate the genomic difference of HBV genotype C between two separated regions, 50 subgenotype Cs-infected Vietnamese and 70 subgenotype Ce-infected Japanese patients were enrolled for analysis. The patients were categorized to either a hepatocellular carcinoma group (HCC) or a non-HCC group including liver cirrhosis, chronic hepatitis, and asymptomatic carriers. HBV serology, HBV-DNA level, and variations in core promoter/pre-core region were examined. Phylogenetic analysis based on the full genome sequences and nucleotide sequences partly in the S gene and in the P gene revealed that all Japanese strains (70/70) were subgenotype Ce, and nearly all of the Vietnamese strains (50/51) were subgenotype Cs, excluding one subgenotype C5. C1858 and G1775 were common in the Vietnamese (64% and 40%) but not in the Japanese (0%). The prevalence of C/A1753 in Vietnamese was higher than that in the Japanese (32% vs. 17.1%), however the frequency of A1896 in the Japanese was significantly higher (32.9% vs. 12%, P < 0.05). Most of the Vietnamese patients with HCC had a high level of HBV-DNA, the Japanese HCC had a relatively low level. In the Vietnamese, C/A1753 and C1858 were associated closely with T1762A1764, higher HBV-DNA levels and higher HCC incidence. The multivariate analysis revealed that male, T1653 and C/A1753 were independent risk factors for HCC. The subgenotypes and unique mutations of HBV genotype C in the Vietnamese and Japanese differed, and C/A1753 and C1858 variants might play a role in the pathogenesis of liver disease in Vietnamese patients.

  1. Complementary and alternative medicine use by visitors to rural Japanese family medicine clinics: results from the international complementary and alternative medicine survey.

    PubMed

    Shumer, Gregory; Warber, Sara; Motohara, Satoko; Yajima, Ayaka; Plegue, Melissa; Bialko, Matthew; Iida, Tomoko; Sano, Kiyoshi; Amenomori, Masaki; Tsuda, Tsukasa; Fetters, Michael D

    2014-09-25

    There is growing interest in the use of complementary and alternative medicine (CAM) throughout the world, however previous research done in Japan has focused primarily on CAM use in major cities. The purpose of this study was to develop and distribute a Japanese version of the International Complementary and Alternative Medicine Questionnaire (I-CAM-Q) to assess the use of CAM among people who visit rural Japanese family medicine clinics. Using a Japanese version of the International Complementary and Alternative Medicine Questionnaire (I-CAM-Q), a cross-sectional survey was conducted in three rural family medicine clinics. All patients and those accompanying patients who met inclusion criteria were eligible to participate. Data were entered into SPSS Statistics and analyzed for use by age, gender, and location. Of the 519 respondents who participated in the project, 415 participants reported CAM use in the past 12 months (80.0%). When prayer is excluded, the prevalence of CAM use drops to 77.3% in the past year, or 403 respondents. The most common forms of CAM used by respondents were pain relief pads (n = 170, 32.8%), herbal medicines/supplements (n = 167, 32.2%), and massage by self or family (n = 166, 32.0%). Female respondents, individuals with higher levels of education, and those with poorer overall health status were more likely to use CAM than respondents without these characteristics. Only 22.8% of CAM therapies used were reported to physicians by survey participants. These data indicate that CAM use in rural Japan is common. The results are consistent with previous studies that show that Japanese individuals are more interested in forms of CAM such as pain relief pads and massage, than in mind-body forms of CAM like relaxation and meditation. Due to the high utilization of certain CAM practices, and given that most CAM users do not disclose their CAM use to their doctors, we conclude that physicians in rural Japan would benefit by asking about CAM use

  2. Physical and sexual abuse histories in patients with eating disorders: a comparison of Japanese and American patients.

    PubMed

    Nagata, T; Kaye, W H; Kiriike, N; Rao, R; McConaha, C; Plotnicov, K H

    2001-08-01

    Physical and sexual abuse among patients with eating disorders has been a focus of attention in Western countries, however, there is no study comparing the incidence of these factors in Western and Asian countries. Japanese subjects consisted of 38 patients with anorexia nervosa restricting type (AN-R), 46 patients with anorexia nervosa binge eating/purging type (AN-BP), 76 patients with bulimia nervosa purging type (BN) and 99 controls. Subjects from the USA consisted of 29 AN-R, 34 AN-BP and 16 BN. The Physical and Sexual Abuse Questionnaire was administered to all subjects. Minor sexual abuse such as confronting exhibitionism or being fondled by a stranger tended to be more prevalent among Japanese subjects, while victimization by rape or incest was more prevalent among USA subjects. Conversely, physical abuse history was similarly distributed across each diagnostic subgroup in both countries. Events related to physical abuse, such as an abusive family background, may contribute whether eating disorder patients are restricting or bulimic and regardless of culture.

  3. Comparison of Nutritional Risk Scores for Predicting Mortality in Japanese Chronic Hemodialysis Patients.

    PubMed

    Takahashi, Hiroshi; Inoue, Keiko; Shimizu, Kazue; Hiraga, Keiko; Takahashi, Erika; Otaki, Kaori; Yoshikawa, Taeko; Furuta, Kumiko; Tokunaga, Chika; Sakakibara, Tomoyo; Ito, Yasuhiko

    2017-05-01

    Protein energy wasting (PEW) is consistently associated with poor prognosis in hemodialysis (HD) patients. We compared the predictability of PEW as diagnosed by The International Society of Renal Nutrition and Metabolism criteria (PEWISRNM) and geriatric nutritional risk index (GNRI) for all-cause mortality in Japanese HD patients. As cut-off values for body mass index (BMI) for PEW have not been established in PEWISRNM for Asian populations, these were also investigated. The nutritional status from 409 HD patients was evaluated according to ISRNM and GNRI criteria. To compare the predictability of mortality, C-index, net reclassification improvement (NRI) and integrated discrimination improvement were evaluated. During follow-up (median, 52 months; range, 7 months), 70 patients (17.1%) presented PEW according to ISRNM and 131 patients (32.1%) according to GNRI; in addition, 101 patients (24.7%) died. PEWISRNM and GNRI were identified as independent predictors of death. Addition of PEWISRNM and GNRI to a predictive model based on established risk factors improved NRI and integrated discrimination improvement. However, no differences were found between models including PEWISRNM and GNRI. When lowering the criterion level of BMI per 1 kg/m(2) sequentially, PEWISRNM at BMI <20 kg/m(2) maximized the hazard ratio for mortality. The model including PEWISRNM at BMI <20 kg/m(2) improved NRI compared with the model including GNRI. PEWISRNM and GNRI represent independent predictors of mortality, with comparable predictability. The diagnostic criterion of BMI in the ISRNM for Japanese population might be better at <20 kg/m(2) than at <23 kg/m(2). Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  4. Incidence of herpes zoster in Japanese patients with rheumatoid arthritis from 2005 to 2010.

    PubMed

    Nakajima, Ayako; Urano, Wako; Inoue, Eisuke; Taniguchi, Atsuo; Momohara, Shigeki; Yamanaka, Hisashi

    2015-07-01

    To clarify the incidence and the risks of herpes zoster infection in Japanese patients with rheumatoid arthritis (RA). By using a self-report of occurrence of herpes zoster in patients with RA in a large observational cohort study from 2005 to 2010, the standardized incidence rate was calculated. A Cox model was used to analyze risk factors for occurrence of herpes zoster. A total of 7,986 patients (female 83.1%) accumulated 30,140 patient-years of observation, and 366 events were confirmed. The standardized incidence rate per 1,000 patient-years was 9.1 (95% confidence interval (CI) 6.2-12.9) in total, 7.8 (3.6-14.8) in men, and 10.3 (6.8-15.0) in women. The risk factors for herpes zoster were age [/10 years: Hazard ratio (HR) 1.268, 95% CI 1.153-1.393, p < 0.0001), high disease activity compared with remission (HR 1.642, 95% CI 1.067-2.528, p < 0.05), prednisolone (< 5 mg/day compared with 0 mg/day: HR 1.531, 95% CI 1.211-1.936, p < 0.001; ≥ 5 mg/day compared with 0 mg/day: HR 1.471, 95% CI 1.034-2.093, p < 0.05), and methotrexate (HR 1.382, 95% CI 1.076-1.774, p < 0.05). This study quantified the historical incidence and risk for herpes zoster in Japanese RA patients, and is a benchmark for future studies.

  5. Effect of azilsartan versus candesartan on morning blood pressure surges in Japanese patients with essential hypertension.

    PubMed

    Rakugi, Hiromi; Kario, Kazuomi; Enya, Kazuaki; Sugiura, Kenkichi; Ikeda, Yoshinori

    2014-06-01

    Morning blood pressure (BP) surge is reported as a risk factor for cardiovascular events and end-organ damage independent of the 24-h BP level. Controlling morning BP surge is therefore important to help prevent onset of cardiovascular disease. We compared the efficacy of azilsartan and candesartan in controlling morning systolic BP (SBP) surges by analyzing relevant ambulatory BP monitoring data in patients with/without baseline BP surges. As part of a 16-week randomized, double-blind study of azilsartan (20-40 mg once daily) and candesartan (8-12 mg once daily) in Japanese patients with essential hypertension, an exploratory analysis was carried out using ambulatory BP monitoring at baseline and week 14. The effects of study drugs on morning BP surges, including sleep trough surge (early morning SBP minus the lowest night-time SBP) and prewaking surge (early morning SBP minus SBP before awakening), were evaluated. Patients with sleep trough surge of at least 35 mmHg were defined by the presence of a morning BP surge (the 'surge group'). Sleep trough surge and prewaking surge data were available at both baseline and week 14 in 548 patients, 147 of whom (azilsartan 76; candesartan 71) had a baseline morning BP surge. In surge group patients, azilsartan significantly reduced both the sleep trough surge and the prewaking surge at week 14 compared with candesartan (least squares means of the between-group differences -5.8 mmHg, P=0.0395; and -5.7 mmHg, P=0.0228, respectively). Once-daily azilsartan improved sleep trough surge and prewaking surge to a greater extent than candesartan in Japanese patients with grade I-II essential hypertension.

  6. Effect of azilsartan versus candesartan on morning blood pressure surges in Japanese patients with essential hypertension

    PubMed Central

    Kario, Kazuomi; Enya, Kazuaki; Sugiura, Kenkichi; Ikeda, Yoshinori

    2014-01-01

    Morning blood pressure (BP) surge is reported as a risk factor for cardiovascular events and end-organ damage independent of the 24-h BP level. Controlling morning BP surge is therefore important to help prevent onset of cardiovascular disease. We compared the efficacy of azilsartan and candesartan in controlling morning systolic BP (SBP) surges by analyzing relevant ambulatory BP monitoring data in patients with/without baseline BP surges. As part of a 16-week randomized, double-blind study of azilsartan (20–40 mg once daily) and candesartan (8–12 mg once daily) in Japanese patients with essential hypertension, an exploratory analysis was carried out using ambulatory BP monitoring at baseline and week 14. The effects of study drugs on morning BP surges, including sleep trough surge (early morning SBP minus the lowest night-time SBP) and prewaking surge (early morning SBP minus SBP before awakening), were evaluated. Patients with sleep trough surge of at least 35 mmHg were defined by the presence of a morning BP surge (the ‘surge group’). Sleep trough surge and prewaking surge data were available at both baseline and week 14 in 548 patients, 147 of whom (azilsartan 76; candesartan 71) had a baseline morning BP surge. In surge group patients, azilsartan significantly reduced both the sleep trough surge and the prewaking surge at week 14 compared with candesartan (least squares means of the between-group differences −5.8 mmHg, P=0.0395; and −5.7 mmHg, P=0.0228, respectively). Once-daily azilsartan improved sleep trough surge and prewaking surge to a greater extent than candesartan in Japanese patients with grade I–II essential hypertension. PMID:24710336

  7. Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours.

    PubMed

    Yonemori, Kan; Tamura, Kenji; Kodaira, Makoto; Fujikawa, Koshi; Sagawa, Tamotsu; Esaki, Taito; Shirakawa, Tsuyoshi; Hirai, Fumihiko; Yokoi, Yuki; Kawata, Toshio; Hatano, Ben; Takahashi, Yasuo

    2016-09-01

    This was the first Phase I study to assess the safety and tolerability of the tablet formulation of olaparib (Lynparza™), an oral poly(ADP-ribose) polymerase inhibitor, in Japanese patients with advanced solid tumours. The pharmacokinetic profile and antitumour activity of olaparib tablets were also assessed. In this open-label, multicentre study (D081BC00001; NCT01813474), a single dose of olaparib (200 or 300 mg, tablets) was administered on day 1, followed 48 h afterwards by multiple dosing (200 or 300 mg twice daily [bid]) for 28-day cycles. Doses were escalated in successive cohorts, with an expansion cohort enrolled at the highest dose that was confirmed to be tolerable during dose escalation. Twenty-eight patients were enrolled and 23 were treated (n = 4, 7 and 12 at 200, 300 and 300 [expansion] mg bid, respectively). No patients experienced a dose-limiting toxicity, so the maximum tolerated dose was not defined. The most frequent adverse events were nausea (43.5 %), decreased appetite (30.4 %), anaemia (26.1 %) and constipation (26.1 %). No patient had dose reductions, two had dose interruptions, and two discontinued treatment because of adverse events. Absorption of olaparib was rapid following single and multiple dosing, and plasma concentrations declined biphasically after single dosing. No patients had a confirmed antitumour response. Olaparib tablet doses of 200 and 300 mg bid were considered tolerable in Japanese patients with advanced solid tumours. Consistent with the global olaparib programme, 300 mg bid was selected as the recommended tablet dose for future studies. NCT01813474.

  8. Adherence to medication and characteristics of Japanese patients with non-valvular atrial fibrillation.

    PubMed

    Suzuki, Tsuyoshi; Shiga, Tsuyoshi; Omori, Hisako; Tatsumi, Fujio; Nishimura, Katsuji; Hagiwara, Nobuhisa

    2017-09-01

    Adherence to medication plays an important role in the prevention of morbidity and mortality in non-valvular atrial fibrillation (NVAF) patients. The aim of this study is to assess adherence to medication and risk factors for non-adherence in Japanese NVAF patients who are prescribed anticoagulants. A total of 378 outpatients with NVAF who completed self-reported questionnaires were analyzed in this prospective study (mean age 69±12 years; 26% female). Self-reported adherence to cardiovascular drugs including anticoagulants was measured with a modified Siegal scale. Depression was defined as a Patient Health Questionnaire-9 score of ≥10. Univariate and multivariate analyses were performed on several variables to analyze factors affecting non-adherence. In total, 291 (77%) of our patients received warfarin, and the remainder received direct oral anticoagulants. Fifty-two (14%) patients were defined as non-adherent. Univariate analyses showed that age <65 years, ≥2 times daily dosing of cardiovascular drugs and employment, but not depression, were significantly associated with non-adherence, 1.87 (95% CI: 1.01-3.42, p=0.04), 2.97 (95% CI: 1.64-5.49, p<0.01), 2.11 (95% CI: 1.16-3.93, p=0.01), and 0.74 (95% CI: 0.26-2.64), respectively. Multivariate analysis showed that only ≥2 times daily dosing was a significant independent risk factor (HR 3.06, 95% CI: 1.67-5.69, p<0.01). Our study showed that the prevalence of non-adherence to medications was 14% in NVAF patients. Frequent daily dosing was an independent risk factor for non-adherence to medication (UMIN-CTR No. UMIN 000023514). Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  9. Hypodontia patterns and variations in craniofacial morphology in Japanese orthodontic patients.

    PubMed

    Endo, Toshiya; Ozoe, Rieko; Yoshino, Sugako; Shimooka, Shohachi

    2006-11-01

    The purpose of this study was to explore the association of hypodontia patterns and variations in craniofacial morphology in Japanese orthodontic patients. A total of 50 girls with hypodontia (the total group) were selected and categorized into anterior, posterior, and anterior-posterior groups according to the location of the congenitally missing teeth. By using the lateral cephalograms of each subject, 28 angular and 37 linear measurements were made. The cephalometric data were statistically analyzed and compared among the groups and with the Japanese cephalometric standards from 36 age-matched female subjects without hypodontia or malocclusion (the control group). Every hypodontia group showed shorter anterior and overall cranial base lengths, shorter maxillary length, greater retroclination and elongation of mandibular incisors, and a larger interincisal angle than the control group. The total and anterior-posterior groups especially exhibited a significantly more prognathic mandible, larger retroclination of maxillary incisors, and a more counterclockwise-rotated occlusal plane. Furthermore, these skeletal and dental deviations were more remarkable in the anterior-posterior group than in either the anterior or the posterior group. Anterior hypodontia exerted as much influence on craniofacial morphology as posterior hypodontia. When orthodontic treatment is performed on patients with hypodontia, not only the number but also the distribution of missing teeth should be taken into consideration, though there was no significant difference in craniofacial morphology between anterior hypodontia and posterior hypodontia.

  10. Reliability and validity of the Japanese-language version of the physical performance test (PPT) battery in chronic pain patients.

    PubMed

    Sato, Daisuke; Kaneko, Fumiko; Okamura, Hitoshi

    2006-03-30

    To prepare a Japanese-language version of the Physical Performance Test (PPT) Battery and assess its reliability and validity. Activity limitations by pain were evaluated by means of the Japanese-language version of the PPT Battery in 82 patients with chronic pain in the limbs and trunk. Two self-report questionnaires, one related to sensory evaluation of pain, and the other related to affective evaluation of pain, and the Functional Independence Measure (FIM), which evaluates activities of daily living, were simultaneously administered to the subjects. The results for reliability showed that the ICC values for inter-rater reliability and intra-rater reliability were 0.91 or more for every item. The results for validity showed significant associations between the scores for all of the items on the Japanese-language version of the PPT Battery and the total scores on the FIM (p < 0.01). Significant associations were found between 5 of the 8 items on the Japanese-language version of the PPT Battery and affective state due to the pain. The Japanese-language version of the PPT Battery was shown to possess adequate reliability and validity as a scale for evaluating the activity limitations of patients with chronic limb or trunk pain. The results also suggested that it might be possible to improve the activity limitations of patients with chronic pain by improving their affective state in response to the pain.

  11. Comparison of Initial Psychological Treatment Selections by US and Japanese Early-Career Psychiatrists for Patients with Major Depression: A Case Vignette Study.

    PubMed

    Williams, Aya; Nakagawa, Atsuo; Sado, Mitsuhiro; Fujisawa, Daisuke; Mischoulon, David; Smith, Felicia; Mimura, Masaru; Sato, Yuji

    2016-04-01

    The authors compared early-career psychiatrists' selection of psychological treatments for patients with mild to moderate major depressive disorder (MDD) in the US and Japan. A total of 120 early-career psychiatrists from two residency programs in the US and Japan participated in web-based surveys. The psychiatrists selected first- and second-line psychological treatments in response to two case vignettes of patients with mild and moderate MDD. Eighty-one psychiatrists (68%) returned the surveys, of whom 39 (48%) were American and 42 (52%) Japanese. In response to the mild MDD case, more US psychiatrists selected high-intensity psychological treatments (P < 0.001), whereas more Japanese psychiatrists selected low-intensity psychological treatments (P < 0.001). In both countries, more psychiatrists selected psychological treatment than medication. In response to the moderate MDD case, one third of the US psychiatrists selected high-intensity psychological treatments (P < 0.001), whereas half of the Japanese psychiatrists selected low-intensity psychological treatments (P = 0.010). Residency training, availability of psychological treatments, and cultural beliefs may shape differences in treatment selections, which in turn may impact the dissemination and implementation of psychological treatment in clinical practice across cultures.

  12. Gender Differences in In-Hospital Clinical Outcomes after Percutaneous Coronary Interventions: An Insight from a Japanese Multicenter Registry

    PubMed Central

    Numasawa, Yohei; Kohsaka, Shun; Miyata, Hiroaki; Noma, Shigetaka; Suzuki, Masahiro; Ishikawa, Shiro; Nakamura, Iwao; Nishi, Yutaro; Ohki, Takahiro; Negishi, Koji; Takahashi, Toshiyuki; Fukuda, Keiichi

    2015-01-01

    Background Gender differences in clinical outcomes after percutaneous coronary intervention (PCI) among different age groups are controversial in the era of drug-eluting stents, especially among the Asian population who are at higher risk for bleeding complications. Methods and Results We analyzed data from 10,220 patients who underwent PCI procedures performed at 14 Japanese hospitals from September 2008 to April 2013. A total of 2,106 (20.6%) patients were women. Women were older (72.7±9.7 vs 66.6±10.8 years, p<0.001), and had a lower body mass index (23.4±4.0 vs 24.3±3.5, p<0.001), with a higher prevalence of hypertension (p<0.001), hyperlipidemia (p<0.001), insulin-dependent diabetes (p<0.001), renal failure (p<0.001), and heart failure (p<0.001) compared with men. Men tended to have more bifurcation lesions (p = 0.003) and chronic totally occluded lesions (p<0.001) than women. Crude overall complications (14.8% vs 9.5%, p<0.001) and the rate of bleeding complications (5.3% vs 2.8%, p<0.001) were significantly higher in women than in men. On multivariate analysis in the total cohort, female sex was an independent predictor of overall complications (OR, 1.47; 95% CI, 1.26–1.71; p<0.001) and bleeding complications (OR, 1.74; 95% CI, 1.36–2.24; p<0.001) after adjustment for confounding variables. A similar trend was observed across the middle-aged group (≥55 and <75 years) and old age group (≥75 years). Conclusions Women are at higher risk than men for post-procedural complications after PCI, regardless of age. PMID:25635905

  13. Salivary enzyme levels after scaling and interleukin-1 genotypes in Japanese patients with chronic periodontitis.

    PubMed

    Yoshie, Hiromasa; Tai, Hideaki; Kobayashi, Tetsuo; Oda-Gou, Emire; Nomura, Yoshiaki; Numabe, Yukihiro; Ito, Kohichi; Kurihara, Hidemi; Kamoi, Kyuichi

    2007-03-01

    Saliva has been used as a diagnostic fluid in medicine and dentistry. It is easy to collect using non-invasive methods. The intracellular enzymes present in saliva have been studied as markers of periodontal disease. The purpose of this study was to determine the salivary enzyme levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) after scaling and to clarify the influence of interleukin (IL)-1 genotypes on these enzyme levels. Forty-nine Japanese patients with chronic periodontitis (24 men and 25 women; mean age: 55.1 years) were enrolled in this study. Measurements of clinical parameters including probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) and collections of stimulated whole mixed saliva were performed at baseline and 4 weeks after scaling. After evaluation of salivary AST, ALT, and LDH levels, DNA was extracted from various cells in whole saliva. IL-1A+4845 G/T genotype was determined by polymerase chain reaction amplification, followed by enzyme digestion and electrophoresis. Statistical analysis was performed by the Wilcoxon signed-rank and Mann-Whitney U tests. A significant difference was set at P <0.05. Mean PD, CAL, and BOP values significantly decreased after scaling (mean +/- SE: 3.2 +/- 0.1 mm to 2.6 +/- 0.1 mm in PD; 3.9 +/- 0.2 mm to 3.3 +/- 0.2 mm in CAL; and 41% +/- 4% to 18% +/- 3% in BOP) (P <0.001). The values of AST, ALT, and LDH were 77.0 +/- 7.5, 43.9 +/- 5.5, and 753.4 +/- 96.5 (units per liter [U/l]) at baseline, and significantly decreased to 55.5 +/- 6.5, 30.0 +/- 5.5, and 394.7 +/- 34.0 (U/l) after scaling, respectively (P = 0.01, P = 0.006, and P <0.001). The carriage rate of the IL-1A+4845 allele 2 was 24.5%. No difference was noted in the decrease in PD, CAL, and BOP after scaling between the carriers (N = 12) and non-carriers (N = 37) of IL-1A+4845 allele 2. However, the IL-1A allele 2 non-carriers displayed a significant decrease in

  14. Long-term treatment with bosutinib in a phase 1/2 study in Japanese chronic myeloid leukemia patients resistant/intolerant to prior tyrosine kinase inhibitor treatment.

    PubMed

    Takahashi, Naoto; Nakaseko, Chiaki; Kobayashi, Yukio; Miyamura, Koichi; Ono, Chiho; Koide, Yuichiro; Fujii, Yosuke; Ohnishi, Kazunori

    2017-04-13

    This long-term follow-up of a completed phase 1/2 study assessed the safety and efficacy of bosutinib in Japanese Philadelphia chromosome-positive, chronic phase (CP) or advanced phase (ADV) chronic myeloid leukemia patients who were resistant/refractory or intolerant to prior tyrosine kinase inhibitor treatment. This analysis included 63 patients with a median bosutinib follow-up of 132 weeks (range 3‒372). In the CP second-line (2L) cohort, the cumulative major cytogenetic response (MCyR) and major molecular response (MMR) rates throughout the study were 73 and 53%, respectively. In the CP third-line (3L) cohort, the cumulative MCyR and MMR rates throughout the study were 70 and 40%, respectively. Of the eight ADV patients, MCyR was attained or maintained by 50% of patients, and complete hematologic response was attained or maintained by 25% of patients. Progression-free survival rate and overall survival rate at 96 weeks were, respectively, 91 and 98% in CP2L, 88 and 100% in CP3L, and 33 and 50% in ADV patients. The most common adverse events (>50%) reported were diarrhea (95%), nasopharyngitis (57%), and rash (57%). Bosutinib demonstrated durable efficacy and a manageable tolerability profile over long-term use in Japanese patients.ClinicalTrials.gov: NCT00811070.

  15. Social orientation and diabetes-related distress in Japanese and American patients with type 2 diabetes.

    PubMed

    Ikeda, Kaori; Fujimoto, Shimpei; Morling, Beth; Ayano-Takahara, Shiho; Carroll, Andrew E; Harashima, Shin-ichi; Uchida, Yukiko; Inagaki, Nobuya

    2014-01-01

    Recent evidence in cultural and social psychology suggests Eastern cultures' emphasis on harmony and connection with others and Western cultures' emphasis on self-direction and autonomy. In Eastern society, relational harmony is closely linked to people's well-being. The impact of this cultural and social orientation on diabetes-related distress was investigated. Japanese and American patients with type 2 diabetes were surveyed by well-established questionnaire in Japan and in the United States, respectively. The association of personal values for interdependence, perceived emotional support, and the Problem Areas in Diabetes scale (PAID) were analyzed. A positive correlation between interdependence and PAID (r = 0.18; P = 0.025) and a negative correlation between perceived emotional support and PAID (r = - 0.24; P = 0.004) were observed after adjustments for other factors in Japanese data (n = 149), but not in American data (r = 0.00; P = 0.990, r = 0.02; P = 0.917, respectively, n = 50). In Japanese data, the three-factor structure of PAID (negative feelings about total life with diabetes, about living conditions with diabetes, and about treatment of diabetes) was identified, and interdependence showed significant positive correlations with the first and second factors and perceived emotional support showed significant negative correlations with all three factors of PAID. These results suggest that personal values for interdependence may be linked to the level of diabetes-related distress and that the distress may be relieved by perception of emotional support, especially in an interdependent cultural context.

  16. The Glucose-lowering Efficacy of Sitagliptin in Obese Japanese Patients with Type 2 Diabetes.

    PubMed

    Kodera, Ryo; Shikata, Kenichi; Nakamura, Akihiko; Okazaki, Satoru; Nagase, Ryo; Nakatou, Tatsuaki; Haisa, Shigeru; Hida, Kazuyuki; Miyashita, Katsuhiro; Makino, Hirofumi

    2017-01-01

    Objective Dipeptidyl peptidase-4 (DPP-4) inhibitors are the most frequently prescribed oral hypoglycemic agents in Japan. Although a relationship between the efficacy of DPP-4 inhibitors and the body mass index (BMI) has been reported, this relationship is controversial. We investigated whether the BMI value affects the glucose-lowering efficacy of sitagliptin in obese Japanese patients with type 2 diabetes. Methods One hundred sixty-two outpatients with inadequate glycemic control were divided into four groups based on their baseline BMI values. They were then treated with sitagliptin (a DPP-4 inhibitor) for 3 months and followed-up for 12 months. Results Sitagliptin significantly reduced the hemoglobin A1c level (HbA1c: -0.71±0.55%) after 3 months, and continued to reduce the HbA1c level until 12 months. There was no significant difference in the efficacy of sitagliptin among the four BMI groups. A multiple linear regression analysis indicated that the factors contributing to the change in the HbA1c level were the baseline level of HbA1c and the homeostasis model assessment of β-cell function (HOMA-β). In terms of the relationship between the baseline BMI value and the efficacy of sitagliptin treatment, the number of patients who responded to sitagliptin treatment after 3 months was lowest in the group of patients with the highest BMI values. A multiple logistic regression analysis revealed that the baseline HOMA-β function and HbA1c level and a baseline BMI value of ≥30 kg/m(2) significantly contributed to the response to sitagliptin treatment. Conclusion The results indicated that sitagliptin treatment was effective in controlling glucose metabolism disorder in obese Japanese patients with type 2 diabetes. However, the efficacy of sitagliptin treatment might be attenuated in severely obese patients, such as those with a BMI value of ≥30 kg/m(2).

  17. A study on task-analysis of clinical pathologists as medical consultants in Nihon University Hospital--a Japanese perspective by comparison with current status in the USA.

    PubMed

    Kumasaka, K; Yanai, M; Hosokawa, N; Iwasaki, Y; Hoshino, T; Arashima, Y; Hayashi, K; Murakami, J; Tsuchiya, T; Kawano, K

    2000-07-01

    To identify our role and the customers' satisfaction, the on-call consultation service records of the Department of Clinical Pathology, Nihon University School of Medicine, Itabashi Hospital (NUIH), were analyzed. Between 1995 and 1998, 1,789 consultation services were recorded, and approximately 40% were from physicians, and 50% were from medical technologists. During office hours, many physicians made contact with us at the office of clinical pathology, the clinical laboratory and other places in the hospital by various means. They asked us to interpret multidisciplinary laboratory data, and to provide the specific information that might affect clinical management. Medical technologists asked for clinical information of patients with extreme measured values and requested that we contact with physicians. In contrast, on weekends/holidays or after routine working hours, physicians sometimes requested non-automated laboratory tests such as peripheral blood smears/bone marrow smears or Gram stains. The major contents of our responses to medical technologists were concerned with blood banking and handling of instruments not to be operated in routine work. These results reconfirm that we are still required to have clinical competence for common laboratory procedures and to have the capability of interpretation of multidisciplinary laboratory data in the university hospital. Traditionally, most Japanese clinical pathologists have been focused their attention on bench work in research laboratories. However, the present study shows that the clinical pathologists need to bridge the real gap between laboratory technology and patient care. Our on-call service system can enhance the education of clinical pathologists, and improve not only laboratory quality assurance but also patient care. In addition, in response to a need for customer access to this service with a shortage of clinical pathologists, a more effective method would be to set up a proactive systemic approach in

  18. Efficacy, safety and pharmacokinetics of indacaterol in Caucasian and Japanese patients with chronic obstructive pulmonary disease: a comparison of data from two randomized, placebo-controlled studies.

    PubMed

    Hosoe, Motoi; Woessner, Ralph; Matsushima, Soichiro; Lawrence, David; Kramer, Benjamin

    2011-01-01

    Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β2-adrenoceptor agonist that has been approved in the EU for the treatment of chronic obstructive pulmonary disease (COPD). Ethnic differences may influence the pharmacokinetics and pharmacodynamics of a drug, and it is therefore important to compare these parameters in different populations. To compare the efficacy, safety and pharmacokinetics of indacaterol between Caucasian and Japanese patients with COPD. Data from two randomized, double-blind, single-dose crossover, placebo-controlled studies in Caucasian and Japanese patients with moderate-to-severe COPD were compared. The two studies were similar in terms of study design, study population (inclusion/exclusion criteria), parameters examined and the indacaterol doses (150, 300 or 600 μg) tested. Efficacy (primary endpoint: 24-hour post-dose [trough] forced expiratory volume in 1 second [FEV1]), pharmacokinetics, and safety were assessed for 24 hours post-dose in each treatment period. Fifty-one Caucasian (86.3% male; mean age 61.8 years) patients were randomized into the first study and 50 Japanese (92.0% male; mean age 67.2 years) patients were randomized into the second study; ≥90% of patients completed the studies. In both studies, 24-hour post-dose trough FEV1 was significantly higher for all indacaterol doses versus placebo (p<0.001), with clinically relevant differences of 140 and 130 mL for the lowest (150 μg) dose in the Caucasian and Japanese studies, respectively. In both studies, single doses of indacaterol provided improvements in FEV1 that were sustained for 24 hours (p<0.001 vs placebo at all time points). In both populations, the average maximum serum concentration (Cmax) of indacaterol was observed at the first sampling time point and pharmacokinetic profiles were similar between populations. The increase in exposure (Cmax and area under the serum concentration-time curve from time zero to 24 hours) with increasing

  19. The results of a survey of physicians about the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014 and its clinical use.

    PubMed

    Mogi, Masaki; Hasebe, Naoyuki; Horiuchi, Masatsugu; Shimamoto, Kazuaki; Umemura, Satoshi

    2016-09-01

    The current study investigated physicians' awareness and use of the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014 (JSH2014) and is based on the results of a survey performed by the Publicity and Advertisement Committee of JSH. A questionnaire was used to survey physicians' awareness of the JSH2014, their recommended target blood pressure for hypertensive patients with complications and their use of antihypertensive drugs. Physicians who downloaded a PDF version of JSH2014 during the 6 months after its publication (April-September 2014) were asked to complete an online questionnaire. Of the 7872 respondents, 91% were aware of the JSH and complied partially, mostly or completely with it in their practice. With reference to hypertensive patients, ∼70% of physicians who completed the questionnaire recommended a target blood pressure (BP) of 140/90 mm Hg for an office BP value, and 40% recommended 135/85 mm Hg for a home BP value. Physicians recommended target BP levels of 130/80 mm Hg for patients with diabetes or chronic kidney disease (50-63% of physician surveyed) and for elderly patients with diabetes or kidney disease (45-55% of respondents), whereas they recommended 140/90 mm Hg for elderly patients with low cardiovascular disease risk (56-60% of physician surveyed) and for patients with chronic-phase stroke (40-47% of respondents). The most commonly prescribed combination of antihypertensive drugs was angiotensin receptor blocker (ARB) with calcium channel blocker. In addition, physicians' first choice of drug for patients with diabetes or chronic kidney disease was most often ARB. Overall, the survey results showed that the new recommendations from the JSH2014 accurately reflect daily clinical practices for hypertension management used by Japanese physicians.

  20. Structure of Resilience among Japanese Adult Patients with Type 1 Diabetes: A Qualitative Study.

    PubMed

    Nishio, Ikuko; Chujo, Masami

    2017-03-01

    Resilience is the process of overcoming adversities and difficulties. We clarified the structure of resilience and its motivational power among adult Japanese patients with type 1 diabetes. This is likely to help ensure effective nursing support to empower patients with diabetes and help them recuperate and improve their personal lives. Participants were 17 patients with type 1 diabetes, and data were collected using semi-structured interviews. Participants shared their experiences of coping with self-management and diabetes control issues, the meaning of living with diabetes, and their support from family and friends since their diagnosis. Glaser's grounded theory was used to analyze the data and the results were used to create a new model of resilience for type 1 diabetes. Five categories were extracted: "suffering from a guilty conscience," "suffering from an insulin-dependent body," "social disability," "a driving force to advancement," and "possessing a strategy to live with the disease." The five categories formed two stages: preparatory resilience and resilience formation. Once patients recognized the presence of empathetic others, they could obtain better disease comprehension and cooperation. Recognizing this support system served as a "driving force to advancement" and was termed the "resilience battery." Through the resilience battery, patients shifted from preparatory resilience to "resilience formation," or acquiring "a strategy to live with the disease." To forge patient resilience, nurses should encourage disease comprehension and cooperation among patients' significant others. We further propose that high-quality nursing care would involve supporting patients' inner resilience.

  1. Japan Fracture Observational Study (JFOS): patient characteristics and interim data on the use of daily teriparatide in Japanese patients with osteoporosis.

    PubMed

    Soen, Satoshi; Fujiwara, Saeko; Takayanagi, Ryoichi; Sato, Masayo; Tsujimoto, Mika; Yamamoto, Takanori; Enomoto, Hiroyuki; Krege, John H

    2015-01-01

    This report from the Japan Fracture Observational Study (JFOS) describes the design of the study, baseline characteristics of the patients, and interim results. This is an interim analysis from an ongoing observational study of male and female patients with osteoporosis initiating daily teriparatide treatment observed at baseline, 3, 6 and 12 months. There was no control group. Baseline data were collected on demographic characteristics, medical and osteoporosis history, prior use of medications and health-related quality of life (HRQoL). This interim analysis includes preliminary information concerning incidence of clinical fractures, bone mineral density (BMD), procollagen type 1 aminoterminal propeptide (P1NP), back pain, HRQoL, and adverse events. Baseline observations were completed for 1810 patients; 90.1% were female. Compared with osteoporotic patients treated with teriparatide in other observational studies, those in JFOS were older but had fewer osteoporosis risk factors. The incidence of clinical fractures was 2.9% at 6 months and 3.7% at 12 months. At 12 months, mean BMD was 8.9% higher at the lumbar spine and 0.8% higher at the total hip compared to baseline. At 6 months, the median serum concentration of P1NP was 187.7% higher than at baseline. At 12 months, back pain scores assessed by visual analog scale (VAS) were lower and HRQoL scores were higher than at baseline. No new safety signals were observed. This is the first report from an observational study of daily teriparatide in Japanese osteoporotic patients at high risk of fractures. Patients in JFOS were older but had fewer osteoporosis risk factors than those treated with teriparatide in other observational studies. The interim analysis suggests that the clinical profile of teriparatide in the real world is similar to that observed in clinical trials and observational studies conducted in Europe and the United States.

  2. Current status of achieving blood pressure target and its clinical correlates in Japanese type 2 diabetes.

    PubMed

    Yokoyama, Hiroki; Araki, Shin-Ichi; Kawai, Koichi; Hirao, Koichi; Kurihara, Yoshio; Seino, Hiroaki; Takamura, Hiroshi; Sugimoto, Hidekatsu; Okada, Akira; Maegawa, Hiroshi

    2017-07-21

    To investigate the current status of achieved blood pressure levels in association with the number of antihypertensive drug classes as of 2013, and to explore the clinical correlates with achievement of target blood pressure in a large-scale cohort of Japanese subjects with type 2 diabetes. A nationwide survey was conducted including 12,811 subjects with type 2 diabetes. Subjects were divided by achieved blood pressure, <130/80 or 140/90 mmHg, and the number of drug classes taken. The percentages achieving a blood pressure of <130/80 or 140/90 mmHg were 52.0% and 86.1%, respectively. The prevalence of hypertension, if defined as ≥130/80 mmHg or treated, became 67.9%. Among subjects taking antihypertensive drugs, a blood pressure of <130/80 or <140/90 mmHg was 46.7% and 83.2%, respectively. The percentages of <130/80 mmHg were 55.9% without drugs, 47.1% on 1, 42.5% on 2, 47.2% on 3, and 56.8% on ≥4 drugs, respectively. The most prescribed drugs were renin-angiotensin system inhibitors, followed by calcium channel blockers, diuretics, and β-blockers. The multiple logistic regression analysis indicated that a blood pressure <130/80 mmHg was associated with lower values in age, body mass index, albuminuria, and glomerular filtration rate, higher proportions on targets for HbA1C and lipids, and less retinopathy. In type 2 diabetes, hypertension is common and only 52% achieved <130/80 mmHg, indicating a difficulty in blood pressure lowering. This was correlated with difficulties in glycemic and lipid management, obesity, and vascular complications, implying these clustering to be a serious problem. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. Phase I study of pegylated interferon-alpha-2b as an adjuvant therapy in Japanese patients with malignant melanoma.

    PubMed

    Yamazaki, Naoya; Uhara, Hisashi; Wada, Hidefumi; Matsuda, Kenji; Yamamoto, Keiko; Shimamoto, Takashi; Kiyohara, Yoshio

    2016-10-01

    In the adjuvant setting for malignant melanoma, interferon (IFN)-α-2b and pegylated (PEG) IFN-α-2b were approved in several countries including the USA before these were approved in Japan. To resolve the "drug-lag" issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage II or III malignant melanoma who had undergone surgery, by treating with PEG IFN-α-2b. As with a previously reported phase III study, patients were to receive PEG IFN-α-2b 6 μg/kg per week s.c. during an 8-week induction phase, followed by a maintenance phase at a dose of 3 μg/kg per week up to 5 years. Dose-limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose-limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug-related adverse events (DRAE) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 DRAE included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration-time curve and maximum observed serum concentration were observed between Japanese and historical non-Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. PEG IFN-α-2b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage III malignant melanoma. Because the number of patients was limited, further investigation would be crucial. © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

  4. Change of carotid intima-media thickness is associated with age in elderly Japanese patients without a history of cardiovascular disease.

    PubMed

    Watanabe, Kentaro; Ouchi, Motoshi; Ohara, Makoto; Kameda, Wataru; Susa, Shinji; Oizumi, Toshihide; Wada, Manabu; Suzuki, Tatsuya; Kawanami, Toru; Oba, Kenzo; Kato, Takeo

    2015-08-01

    The present study aimed to evaluate the relationship between the change of carotid intima-media thickness (CIMT) and clinical characteristics in Japanese patients without a history of cardiovascular disease. The study participants were 149 Japanese patients without a history of cardiovascular disease treated in our outpatient department. The in all participants CIMT was measured with ultrasonography at baseline and after a mean interval of 2.4 years. Study participants were divided into a middle-aged group (younger than 65 years: n = 59) and an elderly group (65 years or older: n = 90). The annual CIMT change (ΔCIMT) was calculated, and the associations between ΔCIMT and clinical characteristics, including age, were evaluated in both groups. The ΔCIMT was significantly correlated with age in all participants (r = 0.222; P < 0.05) and in elderly participants (r = 0.234; P < 0.05), but was not correlated with other risk factors. The annual ΔCIMT was significantly higher in elderly participants (0.015 ± 0.096 mm) than in middle-aged participants (-0.018 ± 0.088 mm; P < 0.05). Multivariate linear regression analysis with ΔCIMT as a dependent variable and risk factors as independent variables showed that ΔCIMT was significantly associated with age in all participants (β = 0.002; P < 0.05) and in elderly participants (β = 0.004; P < 0.05), but not with other risk factors. Annual CIMT change is associated with age, rather than with other clinical characteristics, including traditional cardiovascular risk factors, such as diabetes and hypertension, in elderly Japanese patients without a history of cardiovascular disease. © 2014 Japan Geriatrics Society.

  5. Effect of Ranirestat on Sensory and Motor Nerve Function in Japanese Patients with Diabetic Polyneuropathy: A Randomized Double-Blind Placebo-Controlled Study

    PubMed Central

    Satoh, Jo; Kohara, Nobuo; Sekiguchi, Kenji; Yamaguchi, Yasuyuki

    2016-01-01

    We conducted a 26-week oral-administration study of ranirestat (an aldose reductase inhibitor) at a once-daily dose of 20 mg to evaluate its efficacy and safety in Japanese patients with diabetic polyneuropathy (DPN). The primary endpoint was summed change in sensory nerve conduction velocity (NCV) for the bilateral sural and proximal median sensory nerves. The sensory NCV was significantly (P = 0.006) improved by ranirestat. On clinical symptoms evaluated with the use of modified Toronto Clinical Neuropathy Score (mTCNS), obvious efficacy was not found in total score. However, improvement in the sensory test domain of the mTCNS was significant (P = 0.037) in a subgroup of patients diagnosed with neuropathy according to the TCNS severity classification. No clinically significant effects on safety parameters including hepatic and renal functions were observed. Our results indicate that ranirestat is effective on DPN (Japic CTI-121994). PMID:26881251

  6. Absence of causative mutations and presence of autism-related allele in FOXP2 in Japanese autistic patients.

    PubMed

    Li, Hong; Yamagata, Takanori; Mori, Masato; Momoi, Mariko Y

    2005-04-01

    We analyzed the FOXP2 gene, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, for a possible causative mutation in autism. FOXP2 was reported to be mutated in patients with a severe speech and language disorder. FOXP2 was located on chromosome 7q31, which is one of the loci involved in autism. Autism and specific language impairment share some of their clinical phenotypes. In addition, FOXP2 was expressed abundantly in the brain. We screened all of the exons of FOXP2 for causative mutations in 53 Japanese autistic patients using denaturing high-performance liquid chromatography and direct sequencing. A delCAA in exon 5 causing one glutamine deletion in the first polyglutamine tract was detected in four patients and in 2 of 50 control individuals. The frequency of the TT allele with the G to T base change in intron 15 was significantly high in the autistic population. The other base changes included one silent base change (A569G) in exon 5 and three in introns. Our results may suggest a relationship between autism and the FOXP2 gene or a gene located nearby.

  7. Gonadal function, fertility, and reproductive medicine in childhood and adolescent cancer patients: a national survey of Japanese pediatric endocrinologists

    PubMed Central

    Miyoshi, Yoko; Yorifuji, Tohru; Horikawa, Reiko; Takahashi, Ikuko; Nagasaki, Keisuke; Ishiguro, Hiroyuki; Fujiwara, Ikuma; Ito, Junko; Oba, Mari; Kawamoto, Hiroshi; Fujisaki, Hiroyuki; Kato, Masashi; Shimizu, Chikako; Kato, Tomoyasu; Matsumoto, Kimikazu; Sago, Haruhiko; Takimoto, Tetsuya; Okada, Hiroshi; Suzuki, Nao; Yokoya, Susumu; Ogata, Tsutomu; Ozono, Keiichi

    2016-01-01

    Abstract. An increasing number of pediatric cancer patients survive, and treatment-related infertility represents one of the most important issues for these patients. While official guidelines in Japan recommend long-term follow-up of childhood cancer survivors (CCSs), their gonadal function and fertility have not been clarified. To address this issue, we organized a working panel to compile evidence from long-term survivors who received treatments for cancer during childhood or adolescence. In collaboration with members of the CCS Committee of the Japanese Society for Pediatric Endocrinology (JSPE), we conducted a questionnaire survey regarding reproductive function in pediatric cancer patients. A cross-sectional survey was sent to 178 JSPE-certified councilors who were asked to self-evaluate the medical examinations they had performed. A total of 151 responses were obtained, revealing that 143 endocrinologists were involved in the care of CCSs. A quarter of the respondents reported having experienced issues during gonadal or reproductive examinations. Several survivors did not remember or fully understand the explanation regarding gonadal damage, and faced physical and psychological distress when discussing the risk of becoming infertile. Pediatric endocrinologists had anxieties regarding their patients’ infertility and the risk of miscarriage, premature birth, and delivery problems. Only a limited number of endocrinologists had experience with managing childbirth and fertility preservation. Many councilors mentioned the necessity for inter-disciplinary communication among healthcare providers. Both endocrinologists and oncologists should set and follow a uniform clinical guideline that includes management of fertility of CCSs. PMID:27212796

  8. MicroRNA expression in inflamed and noninflamed gingival tissues from Japanese patients.

    PubMed

    Ogata, Yorimasa; Matsui, Sari; Kato, Ayako; Zhou, Liming; Nakayama, Yohei; Takai, Hideki

    2014-12-01

    Periodontitis is a chronic inflammatory disease caused by specific bacteria and viruses. Local, systemic, and environmental factors affect the rate of disease progression. Immune responses to bacterial products, and the subsequent production of inflammatory cytokines, are crucial in the destruction of periodontal tissue. MicroRNAs (miRNAs) are a class of small RNAs that control various cell processes by negatively regulating protein-coding genes. In this study, we compared miRNA expression in inflamed and noninflamed gingival tissues from Japanese dental patients. Total RNAs were isolated from inflamed and noninflamed gingival tissues. miRNA expression profiles were examined by an miRNA microarray, and the data were analyzed by GeneSpring GX, Ingenuity Pathways Analysis, and the TargetScan databases. Observed miRNA expression levels in inflamed gingiva were confirmed by real-time PCR. The three most overexpressed (by >2.72-fold) miRNAs were hsa-miR-150, hsa-miR-223, and hsa-miR-200b, and the three most underexpressed (by <0.39-fold) miRNAs were hsa-miR-379, hsa-miR-199a-5p, and hsa-miR-214. In IPA analysis, hsa-miR-150, hsa-miR-223, and hsa-miR-200b were associated with inflammatory disease, organismal injury, abnormalities, urological disease, and cancer. The present findings suggest that miRNAs are associated with chronic periodontitis lesions in Japanese.

  9. Ipragliflozin effectively reduced visceral fat in Japanese patients with type 2 diabetes under adequate diet therapy.

    PubMed

    Yamamoto, Chiho; Miyoshi, Hideaki; Ono, Kota; Sugawara, Hajime; Kameda, Reina; Ichiyama, Mei; Yamamoto, Kohei; Nomoto, Hiroshi; Nakamura, Akinobu; Atsumi, Tatsuya

    2016-06-30

    To investigate if ipragliflozin, a novel sodium-glucose co-transporter 2 inhibitor, alters body composition and to identify variables associated with reductions in visceral adipose tissue in Japanese patients with type 2 diabetes mellitus. This prospective observational study enrolled Japanese participants with type 2 diabetes mellitus. Subjects were administered ipragliflozin (50 mg/day) once daily for 16 weeks. Body composition, visceral adipose tissue volume and plasma variables were measured at 0, 8, and 16-weeks. The subjects' lifestyle habits including diet and exercise were evaluated at baseline and 16 weeks. The primary endpoint was defined as the decrease of visceral adipose tissue mass. Twenty-four of 26 enrolled participants completed the study. The visceral adipose tissue decreased significantly (110 ± 33 to 101 ± 36 cm(2), p = 0.005) as well as other parameters for metabolic insufficiency including hemoglobin A1c. Seventy-one % of the total body weight reduction (-2.49 kg) was estimated by a decrease in fat mass (-1.77 kg), and the remaining reduction (22%) by water volume (-0.55 kg). A minor but significant reduction in the skeletal muscle index was also observed. Correlation analyses were performed to identify variables associated with changes in visceral adipose tissue and the only significant variable identified was diet therapy (Spearman's r = -0.416, p = 0.043). Ipragliflozin significantly decreased visceral adipose tissue, and improved parametres for metabolic dysfunction. Adequate diet therapy would be necessary to induce and enhance the therapeutic merit.

  10. A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer.

    PubMed

    Ishiguro, Megumi; Watanabe, Toshiaki; Yamaguchi, Kensei; Satoh, Taroh; Ito, Hideyuki; Seriu, Taku; Sakata, Yuh; Sugihara, Kenichi

    2012-04-01

    Cetuximab (Erbitux(®)) was approved for the treatment of metastatic colorectal cancer in Japan in 2008. To verify information on the safety in practical use of cetuximab, we conducted post-marketing surveillance in accordance with the conditions for approval. All patients to be treated with cetuximab were enrolled by the central enrolment method. Data on treatment status, and incidence and severity of adverse drug reactions were collected. The target number of patients was 1800. A total of 2126 patients were enrolled from 637 institutions. Among 2006 patients analysed, 93.2% received cetuximab as third-line or later treatment. The median duration of treatment was 15.3 weeks, and 11.1% of patients received treatment for >48 weeks. The incidence of adverse drug reactions was 89.6%, of which ≥grade 3 was 21.5%. The incidence of infusion reactions was 5.7% (any grade), with 83.3% of them occurring at the first administration. The incidence of skin disorders was 83.7% (any grade), and the time to event varied for each skin disorder. The incidence of interstitial lung diseases was 1.2% (any grade). Diarrhoea and haematotoxicity scarcely occurred with cetuximab alone. In this surveillance, the incidence and categories of adverse drug reactions are not distinct from previous reports. Although most patients received cetuximab as third-line or later treatment, treatment was maintained with a median duration of 15 weeks. Cetuximab treatment in practical use is considered to be well tolerated and clinically useful in Japanese patients with metastatic colorectal cancer.

  11. Outcome of different post-orchiectomy management for stage I seminoma: Japanese multi-institutional study including 425 patients

    PubMed Central

    Kamba, Tomomi; Kamoto, Toshiyuki; Okubo, Kazutoshi; Teramukai, Satoshi; Kakehi, Yoshiyuki; Matsuda, Tadashi; Ogawa, Osamu

    2010-01-01

    Objectives: To clarify the contemporary clinical outcome of stage I seminoma and to provide information on treatment options to patients. Methods: A retrospective analysis of 425 patients who underwent orchiectomy for stage I seminoma between 1985 and 2006 at 25 hospitals in Japan. Relapse-free survival rates were calculated using the Kaplan–Meier method and clinicopathological factors associated with relapse were examined by univariate and multivariate analyses using the Cox proportional hazards model. Results: A total of 30 out of 425 patients had relapsed. Relapse-free survival rates at 10 years were 79, 94 and 94% in the surveillance, chemotherapy and radiotherapy groups, respectively. Post-orchiectomy management and rete testis invasion were identified as independent predictive factors associated with relapse. Rete testis invasion remained to be an independent predictive factor, even if the cases with relapses in the contralateral testis were censored. Only one patient, who relapsed after adjuvant radiotherapy, died of the disease. Overall survival at 10 years was 100, 100 and 99% in the surveillance, chemotherapy and radiotherapy groups, respectively. More than half of the patients were lost to follow up within 5 years. Conclusions: The outcome of Japanese patients with stage I seminoma is similar to previously published Western reports. Surveillance policy is becoming a popular option in Japan, although the relapse rate in patients opting for surveillance policy is higher than those opting for adjuvant chemotherapy or radiotherapy. Rete testis invasion is an independent predictive factor associated with relapse regardless of the post-orchiectomy management. Long-term follow up is mandatory for detection of late relapse. PMID:20955354

  12. Responsiveness of the Japanese version of the patient-rated wrist evaluation (PRWE-J) and physical impairment measurements in evaluating recovery after treatment of ulnocarpal abutment syndrome.

    PubMed

    Omokawa, Shohei; Imaeda, Toshihiko; Sawaizumi, Takuya; Momose, Toshimitsu; Gotani, Hiroyuki; Abe, Yukio; Moritomo, Hisao; Kanaya, Fuminori

    2012-09-01

    We evaluated the responsiveness of patient-derived questionnaires and physical findings in evaluating recovery after treatment of ulnocarpal abutment syndrome. Patients were assessed at their initial visit to our clinic and again 3 months after the treatment. At each visit, patients completed a Short Form-36, the Japanese Society for Surgery of the Hand version of Disability of the Arm, Shoulder, and Hand questionnaire (DASH-JSSH), and the Japanese version of patient-rated wrist evaluation (PRWE-J). Grip strength, range of motion, and visual analogue scale for wrist pain were also examined at each visit. Satisfaction with treatment was questioned after 3 months using a Likert scale. Standardized response means (SRM) and effect sizes were calculated to evaluate the responsiveness. The PRWE-J (SRM, 1.35) was the most responsive questionnair