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Sample records for japanese patients clinically

  1. [Brain MRI findings in Japanese patients with clinically isolated syndrome].

    PubMed

    Tanaka, Masami; Motoyama, Rie; Tahara, Masayuki; Tanaka, Keiko

    2012-01-01

    Treatment of patients with clinically isolated syndrome (CIS) with disease modifying drugs including interferon β delays conversion to clinically definite multiple sclerosis (MS). However, CIS patients do not necessarily develop MS even after 20 years. Brain MRI lesions were required for CIS patients to include in clinical trials such as CHAMPS study and BENEFIT study. CIS patients with brain MRI lesions compatible to MS were considered as high risk to convert to MS in western countries. Previously we reported that asymptomatic enhancing brain lesions (AEBLs) were found in 9/23 (39.1%) of MS patients who had suffered at least one relapse in the preceding year or two relapses in the preceding 2 years, and the number of AEBLs per scan was 0.37, suggesting low disease activity of Japanese MS patients. We examined brain MRI findings in Japanese CIS patients and compared with those of Japanese MS patients at the first presentation. We reviewed brain MRI of 23 CIS visited our clinic from December 2007 to October 2010 who fulfilled the criteria proposed by Kappos et al. (2006) and Dalton et al (2002). Thirty two clinically definite MS (CDMS) patients fulfilled the first McDonald criteria (two or more attacks and objective clinical evidence of two or more lesions) proposed by Polman et al. (2005). Patients with neuromyelitis optica (NMO) and patients with NMO spectrum proposed by Wingerchuk et al. (2006) and Wingerchuk et al. (2007), respectively, were excluded. Patients with anti-aquaporin4 antibodies or with contiguous spinal cord lesion extending over three vertebral segments on MRI were also excluded. We could not obtain MRI of 11 patients with CDMS because of very long disease course, and 2 CIS and 13 CDMS patients had not been examined with MRI. So we examined 21 CIS and 8 CDMS patients at the first presentation using Paty criteria and Barkhof criteria. Eleven CIS patients did not meet any of the Barkhof criteria. Seven and 3 CIS patients met one and two of Barkhof

  2. Clinical features of 58 Japanese patients with mosaic neurofibromatosis 1.

    PubMed

    Tanito, Katsumi; Ota, Arihito; Kamide, Ryoichi; Nakagawa, Hidemi; Niimura, Michihito

    2014-08-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutation in the NF1 tumor-suppressor gene, and may sometimes manifest in a mosaic form. "Segmental NF1" is generally assumed to be the result of somatic mosaicism for a NF1 mutation, and patients with mosaic NF1 have typical features of NF1 limited to specific body segments. The clinical features of 58 patients (42 females and 16 males; aged 1-69 years; mean age, 23.4 years) with mosaic NF1 seen at the Jikei University Hospital during 2004-2007 and at the Jikei University Daisan Hospital during 2007-2011, were retrospectively studied. Somatic or gonosomal mosaicism was not investigated. Patients were classified into four groups: (i) pigmentary changes (café-au-lait spots and freckling) only (n = 32); (ii) neurofibromas only (n = 5); (iii) neurofibromas and pigmentary changes (n = 13); and (iv) solitary plexiform neurofibromas (n = 8). The area of involvement was variable. The majority of patients were asymptomatic, except patients with plexiform neurofibromas who presented most commonly with pain or tenderness. Lisch nodules were rarely seen. Only four of our 58 patients (6.9%) had specific NF1 complications, including language delay (n = 1) and bone deformity (n = 3). Two patients were ascertained through their children with generalized NF1. Patients with mosaic NF1 are at low risk of developing disease-associated complications, except patients with plexiform neurofibromas. However, they need to be aware of the small risk of having a child with generalized NF1. PMID:25041723

  3. 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. PMID:17959255

  4. 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. PMID:27086350

  5. 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

  6. Bisphosphonate-related osteonecrosis of jaw (BRONJ) in Japanese population: a case series of 13 patients at our clinic.

    PubMed

    Nomura, Takeshi; Shibahara, Takahiko; Uchiyama, Takeshi; Yamamoto, Nobuharu; Shibui, Takeo; Yakushiji, Takashi; Watanabe, Akira; Muramatsu, Kyotaro; Ogane, Satoshi; Murayama, Masato; Sekine, Riyo; Nakata, Erika; Fujimoto, Yuko

    2013-01-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) affects quality of life and is an important problem for dentists. A Japanese position paper on BRONJ was published in 2010. The purpose of this study was to review clinical data on the treatment of BRONJ obtained at the Clinic of Oral and Maxillofacial Surgery, Tokyo Dental College, Chiba Hospital to further our understanding of this disease. A total of 13 patients (6 men and 7 women) were included. All the patients included in this study had received Bisphosphonate (BP) therapy and had BRONJ. Five of them (38.5%) had received oral BP therapy for osteoporosis, while the remaining 8 (61.5%) had received parenteral BP therapy for bone metastases from breast or prostate cancer. Osteoporosis patients were treated with risedronate or alendronate. Breast or prostate cancer patients were treated with zoledronate. Two patients with rheumatoid arthritis were treated with corticosteroid. Three patients had diabetes mellitus. Eleven patients were treated with antibiotics, while 5 underwent surgical treatment. Discontinuation of BP was recorded in 7 patients during dental treatment. Sequestration was observed in 6 patients during an 11-month follow-up. Eventually, healing and improvement of the oral mucosa were observed in 3 patients. The current standard treatment for BRONJ does not always provide good results. It is necessary to accumulate further clinical data to establish more effective treatment strategies for BRONJ. PMID:23903583

  7. Efficacy and Clinical Characteristics of Liraglutide in Japanese Patients With Type 2 Diabetes

    PubMed Central

    Ito, Daisuke; Iuchi, Takujiro; Kurihara, Susumu; Inoue, Ikuo; Katayama, Shigehiro; Inukai, Kouichi

    2015-01-01

    Background Liraglutide was first released in Japan as a long-acting once-daily glucagon-like peptide-1 receptor agonist. The maximum dose in Japan is 0.9 mg/day, which is half of that used in the United States and the European Union (1.8 mg/day). The efficacy of this maximum allowable dose of liraglutide for Japanese patients and the profiles of those patients for whom this agent should be recommended remain unclear. Methods This study aimed to examine the effective use of liraglutide in Japanese type 2 diabetic patients. We administered liraglutide to 60 patients, who had been managed with oral hypoglycemic agents or diet and exercise therapy only, during a period of 6 months. Results Though HbA1c levels significantly decreased, by approximately 1.5%, after 6 months of liraglutide administration, no significant changes in body weights were observed. The 0.6 mg dose was effective in approximately 40% of patients. In contrast, the effects of a dose increase from 0.6 mg to 0.9 mg were small. The greatest efficacy, as shown by a 2.5% HbA1c decrease, was achieved in non-obese patients. Thus, efficacy decreased as the degree of obesity increased. In addition, efficacy was higher in patients who had a diabetes duration of less than 10 years and was also higher in the group that had a low sulfonylurea (SU) index, when we define the SU index as mg/glimepiride × years of treatment. Conclusions As appetite suppressions and associated decreases in body weights were not observed in obese patients, the efficacy of liraglutide at 0.9 mg did not appear to be high. Rather, it appeared to be highly effective for patients who were non-obese and for whom amelioration of blood glucose elevations could be anticipated via the stimulation of insulin secretion. Therefore, we found that liraglutide at doses of 0.9 mg was highly effective in non-obese patients who were in the early stages of diabetes and was particularly effective in patients who had not yet been administered SU agents

  8. Acute Zonal Occult Outer Retinopathy in Japanese Patients: Clinical Features, Visual Function, and Factors Affecting Visual Function

    PubMed Central

    Saito, Saho; Saito, Wataru; Saito, Michiyuki; Hashimoto, Yuki; Mori, Shohei; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

    2015-01-01

    Purpose To evaluate the clinical features and investigate their relationship with visual function in Japanese patients with acute zonal occult outer retinopathy (AZOOR). Methods Fifty-two eyes of 38 Japanese AZOOR patients (31 female and 7 male patients; mean age at first visit, 35.0 years; median follow-up duration, 31 months) were retrospectively collected: 31 untreated eyes with good visual acuity and 21 systemic corticosteroid-treated eyes with progressive visual acuity loss. Variables affecting the logMAR values of best-corrected visual acuity (BCVA) and the mean deviation (MD) on Humphrey perimetry at initial and final visits were examined using multiple stepwise linear regression analysis. Results In untreated eyes, the mean MD at the final visit was significantly higher than that at the initial visit (P = 0.00002). In corticosteroid-treated eyes, the logMAR BCVA and MD at the final visit were significantly better than the initial values (P = 0.007 and P = 0.02, respectively). The final logMAR BCVA was 0.0 or less in 85% of patients. Variables affecting initial visual function were moderate anterior vitreous cells, myopia severity, and a-wave amplitudes on electroretinography; factors affecting final visual function were the initial MD values, female sex, moderate anterior vitreous cells, and retinal atrophy. Conclusions Our data indicated that visual functions in enrolled patients significantly improved spontaneously or after systemic corticosteroids therapy, suggesting that Japanese patients with AZOOR have good visual outcomes during the follow-up period of this study. Furthermore, initial visual field defects, gender, anterior vitreous cells, and retinal atrophy affected final visual functions in these patients. PMID:25919689

  9. A spectrum of clinical presentations in seven Japanese patients with vitamin d deficiency.

    PubMed

    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

  10. Evaluation of Factors Affecting Continuous Performance Test Identical Pairs Version Score of Schizophrenic Patients in a Japanese Clinical Sample

    PubMed Central

    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. PMID:22966454

  11. Onset of clinical effects and plasma concentration of fluvoxamine in Japanese patients.

    PubMed

    Katoh, Yasuhiro; Uchida, Shinya; Kawai, Masayoshi; Takei, Noriyoshi; Mori, Norio; Kawakami, Junichi; Kagawa, Yoshiyuki; Yamada, Shizuo; Namiki, Noriyuki; Hashimoto, Hisakuni

    2010-01-01

    It is widely accepted that selective serotonin reuptake inhibitors (SSRIs) require 2 to 4 weeks of administration before improvements in emotional symptoms of depression are seen. We evaluated whether early monitoring of Hamilton Rating Scale for Depression (HAMD) scores in patients treated with the SSRI fluvoxamine could predict antidepressant response, and also assessed the relationship between the onset of clinical response following the start of fluvoxamine administration and its plasma concentration. Twelve depressed patients (baseline HAMD score ≥15) received an initial dose of fluvoxamine (50 mg/d) followed by an optimized maintenance dose according to their clinical symptoms after 7 d. HAMD scores and plasma drug concentrations were determined at 7 and 28 d after the first administration. There were 7 responders and 5 non-responders on day 28, as evaluated by HAMD scores. The HAMD score for the responders was significantly lower than that for the non-responders on day 7 (mean±S.D., 11.6±6.1 vs. 26.6±6.5, p=0.006). Thus, the reduction in HAMD score on day 7 was clearly divided between responders and non-responders. On day 28, the plasma concentration of fluvoxamine in responders was lower than that in non-responders (14.2±10.5 ng/ml vs. 44.2±28.1 ng/ml, p=0.051). Furthermore, receiver operating characteristic curve analysis conducted on day 28 revealed an upper concentration threshold of 28.2 ng/ml (p=0.042), with none in the responder group above that level. Our results suggest that HAMD score after the first week of treatment with fluvoxamine and the upper threshold of plasma drug concentration could predict whether a patient is a non-responder. PMID:21139240

  12. Clinical efficacy of oral risedronate therapy in Japanese patients with Paget's disease of bone.

    PubMed

    Ohara, Masaya; Imanishi, Yasuo; Nagata, Yuki; Ishii, Akira; Kobayashi, Ikue; Mori, Katsuhito; Ito, Manabu; Miki, Takami; Nishizawa, Yoshiki; Inaba, Masaaki

    2015-09-01

    Paget's disease of bone (PDB) is a chronic disorder characterized by localized bone regions with excessive bone turnover. Although oral risedronate (17.5 mg daily for 8 weeks) was recently approved in Japan, its efficacy is not well understood. We retrospectively examined the efficacy of oral risedronate in PDB patients in a clinical setting. Eleven patients whose serum alkaline phosphatase (ALP) level exceeded the upper limit of the normal range were treated. Patients whose ALP levels normalized and remained so for 12 months after therapy initiation were defined as responders. Treatment was repeated if bone pain recurred or if serum ALP levels increased at least 25% above the nadir. Six patients (55%) were responsive to the therapy. A higher prevalence of skull lesions, higher serum calcium levels at treatment initiation and antecedent treatments of bisphosphonates were predictors of resistance against the therapy. Fresh frozen serum samples obtained from some treatment sessions were evaluated for metabolic bone markers such as bone-specific ALP (BAP), type I procollagen N-terminal pro-peptide (PINP), N-treminal crosslinking telopeptide of type I collagen and C-treminal crosslinking telopeptide of type I collagen (CTX). A significant reduction of P1NP preceded that of serum ALP levels in the responders, which was followed by a similar occurrence for BAP and osteocalcin (BGP) levels. A temporary decrease in CTX levels was noted. No significant changes in markers (including ALP level) were observed in non-responder and repeat-treatment groups. P1NP levels may be more useful than ALP levels in assessing treatment efficacy. Repeat treatment effectiveness for the repeat-treatment group was limited. PMID:25319558

  13. Clinical, muscle pathological, and genetic features of Japanese facioscapulohumeral muscular dystrophy 2 (FSHD2) patients with SMCHD1 mutations.

    PubMed

    Hamanaka, Kohei; Goto, Kanako; Arai, Mami; Nagao, Koji; Obuse, Chikashi; Noguchi, Satoru; Hayashi, Yukiko K; Mitsuhashi, Satomi; Nishino, Ichizo

    2016-01-01

    Facioscapulohumeral muscular dystrophy 2 (FSHD2) is a genetic muscular disorder characterized by DNA hypomethylation on the 4q-subtelomeric macrosatellite repeat array, D4Z4. FSHD2 is caused by heterozygous mutations in the gene encoding structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1). Because there has been no study on FSHD2 in Asian populations, it is not known whether this disease mechanism is widely seen. To identify FSHD2 patients with SMCHD1 mutations in the Japanese population, bisulfite pyrosequencing was used to measure DNA methylation on the D4Z4 repeat array, and in patients with DNA hypomethylation, the SMCHD1 gene was sequenced by the Sanger method. Twenty patients with D4Z4 hypomethylation were identified. Of these, 13 patients from 11 unrelated families had ten novel and one reported SMCHD1 mutations: four splice-site, two nonsense, two in-frame deletion, two out-of-frame deletion, and one missense mutations. One of the splice-site mutations was homozygous in the single patient identified with this. In summary, we identified novel SMCHD1 mutations in a Japanese cohort of FSHD2 patients, confirming the presence of this disease in a wider population than previously known. PMID:27061275

  14. 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. PMID:22124530

  15. 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. PMID:21618639

  16. 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

  17. Japanese encephalitis virus in meningitis patients, Japan.

    PubMed

    Kuwayama, Masaru; Ito, Mikako; Takao, Shinichi; Shimazu, Yukie; Fukuda, Shinji; Miyazaki, Kazuo; Kurane, Ichiro; Takasaki, Tomohiko

    2005-03-01

    Cerebrospinal fluid specimens from 57 patients diagnosed with meningitis were tested for Japanese encephalitis virus. Total RNA was extracted from the specimens and amplified. Two products had highest homology with Nakayama strain and 2 with Ishikawa strain. Results suggest that Japanese encephalitis virus causes some aseptic meningitis in Japan. PMID:15757569

  18. Phase II clinical study of eribulin monotherapy in Japanese patients with metastatic breast cancer who had well-defined taxane resistance.

    PubMed

    Inoue, Kenichi; Saito, Tsuyoshi; Okubo, Katsuhiko; Kimizuka, Kei; Yamada, Hirofumi; Sakurai, Takashi; Ishizuna, Kazuo; Hata, Satoshi; Kai, Toshihiro; Kurosumi, Masafumi

    2016-06-01

    No clinical evidence on the efficacy and safety of eribulin monotherapy has been obtained by a prospective clinical study in patients with metastatic breast cancer (MBC) who had well-defined taxane resistance. The present Phase II, multicenter, single-arm, open-label study aimed to obtain the evidence. Japanese female patients, aged 33-74 years who had the metastasis of taxane-resistant and histopathologically confirmed breast cancer, received eribulin mesylate 1.4 mg/m(2) (equivalent to eribulin 1.23 mg/m(2) [expressed as free base]) as a 2- to 5-min intravenous infusion on days 1 and 8 of each 21-day cycle. The primary endpoint was the clinical benefit rate (CBR) [complete response (CR), partial response (PR), and long-term stable disease (LSD) ≥24 weeks]. A total of 51 patients underwent chemotherapy cycles (median 4; range 1-42 cycles). The CBR was 39.2 % (CR 2.0 %; PR 23.5 %; and LSD 13.7 %), and the rate of progressive disease was 49.0 %. The median progression-free survival and the median overall survival were 3.6 months [95 % confidence interval (CI) 2.6-4.6 months] and 11.7 months (95 % CI 9.2-14.2 months), respectively. Grade 3 or greater adverse events were leukopenia (23.5 %), neutropenia (35.3 %), anemia (5.9 %), and febrile neutropenia (7.8 %). The incidences of grade 3 and 4 peripheral sensory neuropathy were 2.0 and 0 %, respectively. Eribulin showed a clinically manageable tolerability profile by dose adjustments or symptomatic treatment. Eribulin was effective and well tolerated in heavily pretreated patients with MBC who had well-defined taxane resistance, thus providing a potential therapeutic option in the clinical settings. PMID:27125669

  19. Hospitalization for Hypoglycemia in Japanese Diabetic Patients

    PubMed Central

    Sako, Akahito; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Hamasaki, Hidetaka; Katsuyama, Hisayuki; Tsujimoto, Tetsuro; Goto, Atsushi; Yanai, Hidekatsu

    2015-01-01

    Abstract We aimed to elucidate the epidemiology, patient demographics, and clinical outcomes of hospitalization for hypoglycemia in diabetic patients using a Japanese large-scale database. We conducted a retrospective study using a national inpatient database of acute care hospitals in Japan. Diabetic patients ages ≥15 years with hypoglycemia as a main diagnosis for hospitalization were eligible. We estimated the annual number of hospitalizations in Japan and compared the annual admission rate by age and treatment groups. We also analyzed the association between patient characteristics and in-hospital mortality. Among 22.7 million discharge records from July 2008 and March 2013, a total of 25,071 patients were eligible. The mean age was 73.4 years, and the mean body mass index (BMI) was 22.3 kg/m2. The estimated annual hospitalization for hypoglycemia in Japan was ∼20,000. Annual admission rates for hypoglycemia per 1000 diabetic patients and 1000 diabetic patients receiving insulin or oral hypoglycemic agents were 2.1 and 4.1, respectively. Patients <40 years and >70 years old were at a higher risk of hospitalization. In-hospital mortality was 3.8%, and risk factors associated with poor survival were male sex, older age, lower bed capacity, community hospital, low BMI, coma at admission, and higher Charlson Comorbidity Index. To prevent severe hypoglycemia that leads to death and complications, individualized and careful glycemic control are important, especially in very old or young patients and in those with comorbid conditions or low BMI. PMID:26107672

  20. Post-hoc analysis showing better clinical response with the loading dose of certolizumab pegol in Japanese patients with active rheumatoid arthritis

    PubMed Central

    Takeuchi, Tsutomu; Yamamoto, Kazuhiko; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Kobayashi, Mariko; Shoji, Toshiharu; Togo, Osamu; Miyasaka, Nobuyuki; Koike, Takao

    2016-01-01

    Abstract Objectives: To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Methods: Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. Results: In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Conclusions: Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile. PMID:26472043

  1. A Japanese patient with the Costello syndrome.

    PubMed

    Okamoto, N; Chiyo, H; Imai, K; Otani, K; Futagi, Y

    1994-05-01

    The Costello syndrome is characterized by dwarfism, unique cutaneous lesions, distinct facial gestalt, and mental retardation. We present a Japanese patient with the Costello syndrome. She showed high serum IgM level during the early infantile period. Nissen's fundplication was carried out to treat severe gastroesophageal reflux. Endocrinological investigations revealed a partial deficiency of growth hormone. PMID:8168845

  2. Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial

    PubMed Central

    Ishiguro, Naoki; Takeuchi, Tsutomu; Miyasaka, Nobuyuki; Mukai, Masaya; Matsubara, Tsukasa; Uchida, Shoji; Akama, Hideto; Kupper, Hartmut; Arora, Vipin; Tanaka, Yoshiya

    2014-01-01

    Objective. The aim of this study was to compare efficacy outcomes of initial treatment with adalimumab + MTX vs adalimumab addition following 26 weeks of MTX monotherapy in Japanese early RA patients naive to MTX with high disease activity. Methods. Patients completing the 26-week, randomized, placebo-controlled trial of adalimumab + MTX were eligible to receive 26 weeks of open-label adalimumab + MTX. Patients were assessed for mean change from baseline in the 28-joint DAS with ESR (DAS28-ESR) and modified total Sharp score (mTSS), and for the proportions of patients achieving clinical, functional or radiographic remission. Results. Of 333 patients assessed, 278 (137 from the initial adalimumab + MTX and 141 from the initial placebo + MTX groups) completed the 52-week study. Significant differences in clinical and functional parameters observed during the 26-week blinded period were not apparent following the addition of open-label adalimumab to MTX. Open-label adalimumab + MTX slowed radiographic progression through week 52 in both groups, but patients who received adalimumab + MTX throughout the study exhibited less radiographic progression than those who received placebo + MTX during the first 26 weeks (mean ΔmTSS at week 52 = 2.56 vs 3.30, P < 0.001). Conclusion. Delayed addition of adalimumab in Japanese MTX-naive early RA patients did not impact clinical and functional outcomes at week 52 compared with the earlier addition of adalimumab. However, the accrual of significant structural damage during blinded placebo + MTX therapy contributed to the persistence of differences between the treatment strategies, suggesting that Japanese patients at risk for aggressive disease should benefit from the early inclusion of adalimumab + MTX combination therapy. Trial registration. ClinicalTrials.gov (http://clinicaltrials.gov/), NCT00870467. PMID:24441150

  3. Histopathological Features of Brain Arteriovenous Malformations in Japanese Patients.

    PubMed

    Hermanto, Yulius; Takagi, Yasushi; Yoshida, Kazumichi; Ishii, Akira; Kikuchi, Takayuki; Funaki, Takeshi; Mineharu, Yohei; Miyamoto, Susumu

    2016-06-15

    Clinical features of high risk brain arteriovenous malformations (BAVMs) are well characterized. However, pathological evidences about the differences that are possessed by high risk patients are still lacking. We reviewed archived routine hematoxylin-eosin specimens from a total of 54 surgical treated BAVMs. The histopathological features in nidus were semi-quantitatively analyzed. We obtained the pathological differences of BAVMs nidus between several clinical features. Among the analyzed pathological features, the significant differences were observed in degree of venous enlargement and intimal hyperplasia. Juvenile, female, diffuse nidus, high Spetzler-Martin grade, and low flow patients had a lesser degree of those parameters compared to adult, male, compact nidus, low Spetzler-Martin grade and high flow patients. High risk profiles of BAVMs patients were well-reflected in the nidus pathology. Therefore, juvenile, female, diffuse nidus, and low flow in Japanese BAVMs patients might have different vascular remodeling process that predispose to higher tendency of hemorrhage. PMID:27053330

  4. 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

  5. Neuroradiological Manifestations of Hereditary Hemorrhagic Telangiectasia in 139 Japanese Patients

    PubMed Central

    KOMIYAMA, Masaki; TERADA, Aiko; ISHIGURO, Tomoya; WATANABE, Yusuke; NAKAJIMA, Hideki; YAMADA, Osamu; MORISAKI, Hiroko

    The purpose of this study is to report the neuroradiological manifestations of hereditary hemorrhagic telangiectasia (HHT). One hundred and thirty-nine Japanese HHT patients (73 men and 66 women, aged 2–78 years) were included in this study. Diagnosis of HHT was based on genetic analysis and/or clinical diagnosis of Curaçao. They included 68 HHT1 and 37 HHT2 patients. Essentially, all patients underwent brain magnetic resonance imaging (MRI) and pulmonary computed tomography (CT). Contrast enhanced studies of brain MRI and hepatic CT were performed in a subset of patients. Catheter cerebral angiography was performed when indicated. Their neuroradiological features were reviewed retrospectively. Various imaging abnormalities were found. Brain arteriovenous malformations (AVMs) were observed in 27/136 patients (19.9%, 21 patients with HHT1 and 1 patient with HHT2). Pulmonary arteriovenous fistulas (AVFs) were found in 73/137 patients (65.2%, 45 patients with HHT1 and 6 patients with HHT2). Cerebral infarction and brain abscess were found in 17 patients and 3 patients with pulmonary AVFs, respectively. T1 high lesions in the basal ganglia suggestive of porto-venous shunts were observed in 51/136 patients (37.5%, 9 patients with HHT1 and 28 patients with HHT2). Hepatic AVMs were observed in 61/136 patients (44.9%, 15 patients in HHT1 and 29 patients in HHT2). Brain AVMs and pulmonary AVFs were more common in HHT1 than in HHT2 (both p < 0.01), but hepatic AVMs were conversely more common in HHT2 than in HHT1 (p < 0.01). In conclusion, HHT patients present with a variety of neuroradiological manifestations, which are related to substantial causes of morbid-mortality in HHT. PMID:26041630

  6. Associations between deepness of response and clinical outcomes among Japanese patients with metastatic colorectal cancer treated with second-line FOLFIRI plus cetuximab

    PubMed Central

    Osumi, Hiroki; Matsusaka, Satoshi; Suenaga, Mitsukuni; Shinozaki, Eiji; Mizunuma, Nobuyuki

    2015-01-01

    Background In the FIRE-3 trial, overall survival (OS) was significantly longer in patients treated with FOLFIRI plus cetuximab (C-mab) than in those treated with FOLFIRI plus bevacizumab (Bev), but progression-free survival (PFS) was not significantly different. This may be associated with the deepness of response (DpR) in patients treated with FOLFIRI plus C-mab. We aimed to evaluate the relationship between clinical outcome and DpR in metastatic colorectal cancer (mCRC) patients treated with second-line FOLFIRI plus C-mab. Methods A total of 112 patients with histopathologically confirmed mCRC treated with second-line FOLFIRI in combination with C-mab (N=42) or Bev (N=70) were retrospectively enrolled between October 2008 and June 2013. The relationship between DpR and clinical outcome in patients treated with FOLFIRI plus C-mab or Bev was determined. Results Forty-two patients treated with FOLFIRI plus C-mab had a mean DpR of 6.1% (inter-quartile range: −13.7%, 20.8%) and a minimum DpR of −62.7%. On the other hand, 70 patients treated with FOLFIRI plus Bev had a mean DpR of 0% (interquartile range: −16%, 10%) and a minimum DpR of −111%. DpR ≥30% was associated with significantly longer OS and PFS when compared with DpR ≤30% in patients given FOLFIRI plus C-mab. DpR (≥30%) was independently associated with prolongation of OS and PFS. In patients treated with FOLFIRI plus C-mab, there was a moderate positive correlation between DpR and clinical outcomes (OS: r=0.51, P<0.001; PFS: r=0.54, P<0.001). Conclusion FOLFIRI plus C-mab yielded a stronger correlation between DpR and clinical outcomes. These results indicate the potential of DpR as a new measure of efficacy in mCRC patients treated with second-line chemotherapy plus C-mab. PMID:26273206

  7. 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.

  8. Characteristics of elderly Japanese patients with severe burns.

    PubMed

    Morita, Seiji; Higami, Shigeo; Yamagiwa, Takeshi; Iizuka, Shinichi; Nakagawa, Yoshihide; Yamamoto, Isotoshi; Inokuchi, Sadaki

    2010-11-01

    In this study, we report the clinical characteristics of elderly Japanese patients with severe burns. We studied the clinical features of 76 adult patients with severe burns, 35 of whom (46.1%) were ≥65 years old. We evaluated the characteristics of patients with respect to each type of burn. In addition, we studied the rate of death and survival in the elderly and also between the elderly and non-elderly patients. The following parameters were either assessed or compared between the elderly and non-elderly: gender, average age, vital signs (Glasgow Coma Scale, systolic blood pressure, heart rate and respiratory rate) and PaO(2)/FiO(2) (P/F) ratio at admission, cause of burn and a history of physical or psychiatric disease. Further, we investigated whether the burn was caused by attempting suicide and determined the percent total body surface area (%TBSA), second- and third-degree burn area, burn index (BI), prognostic burn index (PBI), presence of tracheal burns, presence of alcohol intoxication and overdose poisoning, presence of tracheal intubation, outcome and cause of death. The male:female ratio of the elderly patients was 17:18 (average age, 78.1 (8.2) years). Burns were mostly caused by flame (26/35), followed by scalding (8/35). Ten patients had attempted suicide. The %TBSA, second-degree burn area, third-degree burn area, BI and PBI, respectively were 46.6% (26.7%), 15.3% (19.0%), 35.6% (26.0%), 41.1 (25.2) and 119.2 (25.9). Of the 35 patients, 23 died. The notable characteristics of the elderly patients who died were flame as the cause of the burns: high %TBSA, BI and PBI, and a high rate of tracheal intubation. Elderly patients constituted approximately 45% of our study population. Most burns were caused by flames. The incidence of accidental bathtub-related burns was higher and that of suicide attempts was lower in the elderly patients, as compared with the non-elderly patients. Severe burns were fatal for elderly patients. Therefore, elderly

  9. A cross-sectional analysis of quality of life in Japanese acne patients using the Japanese version of Skindex-16.

    PubMed

    Hayashi, Nobukazu; Higaki, Yuko; Kawamoto, Kyoko; Kamo, Toshiko; Shimizu, Satoru; Kawashima, Makoto

    2004-12-01

    We measured the quality of life of Japanese patients with acne using the Japanese version of Skindex-16, a semantically equivalent and validated translation of the original version produced by Chren et al. A total of 210 acne patients were enrolled in this study. The results showed that patients with acne experienced more severe emotional effects from their skin disease than functional or symptomatic effects. The scores for emotional aspects were related to the severity of the patients' acne following a prescribed scale, but the scores were high even when the patients only had a few comedones. Akaike's information criterion showed that the scores for symptoms were related to the severity of the patients' acne, and the patients' emotions were related to the interval between clinic visits. To improve patients' quality of life, treatment of comedones should be fully respected. In addition, dermatologists should encourage patients to visit clinics regularly to help them improve the emotional aspects of their quality of life. PMID:15801260

  10. Traditional Japanese Medicine Daikenchuto Improves Functional Constipation in Poststroke Patients

    PubMed Central

    Numata, Takehiro; Takayama, Shin; Tobita, Muneshige; Ishida, Shuichi; Katayose, Dai; Shinkawa, Mitsutoshi; Oikawa, Takashi; Aonuma, Takanori; Kaneko, Soichiro; Tanaka, Junichi; Kanemura, Seiki; Iwasaki, Koh; Ishii, Tadashi; Yaegashi, Nobuo

    2014-01-01

    Poststroke patients with functional constipation, assessed by the Rome III criteria, from 6 hospitals were recruited in a study on the effects of the traditional Japanese medicine Daikenchuto (DKT) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the DKT group received 15 g/day of DKT for 4 weeks. Constipation scoring system (CSS) points and the gas volume score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) were recorded before and after a 4-week observation period. The total score on the CSS improved significantly in the DKT group compared to the control (P < 0.01). In addition, scores for some CSS subcategories (frequency of bowel movements, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the DKT group (P < 0.01, P = 0.049, and P = 0.03, resp.). The GVS was also significantly reduced in the DKT group compared to the control (P = 0.03). DKT in addition to conventional therapy is effective in treating functional constipation in poststroke patients. This study was a randomized controlled trial and was registered in the UMIN Clinical Trial Registry (no. UMIN000007393). PMID:25089144

  11. The Inequality of Patient Profile Information in Japanese Hospitals.

    PubMed

    Kurihara, Yukio; Ishida, Haku; Kimura, Ezen; Gochi, Akira; Kondoh, Hiroshi; Shimai, Ken-Ichiro; Nakajima, Noriaki; Tanaka, Takeshi; Ishikawa, Kiyomu; Oohara, Michihiro; Sonoda, Takeharu; Takai, Kohei

    2016-01-01

    A model dataset of patient profile information was created based on the items used at five Japanese university hospitals, the patient information data elements in Health Level 7 (HL7) v2.5, and the standard datasets for medical information exchange used in Japan. In order to check the validity of the model dataset, a cross-sectional survey was performed. A preliminary analysis of 20 Japanese hospitals found that most items were implemented at some hospitals, but the number of items implemented at many hospitals was rather small. This result strongly shows the necessity for a standardized dataset of patient profile information. PMID:27577415

  12. Genetic characteristics of Japanese clinical Listeria monocytogenes isolates.

    PubMed

    Miya, Satoko; Takahashi, Hajime; Nakagawa, Miku; Kuda, Takashi; Igimi, Shizunobu; Kimura, Bon

    2015-01-01

    Listeria monocytogenes causes foodborne illnesses through consumption of ready-to-eat foods. Although 135-201annual listeriosis cases have been estimated in Japan, the details regarding the clinical isolates such as infection source, virulence level, and other genetic characteristics, are not known. In order to uncover the trends of listeriosis in Japan and use the knowledge for prevention measures to be taken, the genetic characteristics of the past human clinical isolates needs to be elucidated. For this purpose, multilocus tandem-repeat sequence analysis (MLTSA) and multi-virulence-locus sequence typing (MVLST) were used in this study. The clinical isolates showed a variety of genetically distant genotypes, indicating they were from sporadic cases. However, the MVLST profiles of 7 clinical isolates were identical to those of epidemic clone (EC) I isolates, which have caused several serious outbreaks in other countries, suggesting the possibility that they have strong virulence potential and originated from a single outbreak. Moreover, 6 Japanese food isolates shared their genotypes with ECI isolates, indicating that there may be risks for listeriosis outbreak in Japan. This is the first investigational study on genetic characteristics of Japanese listeriosis isolates. The listeriosis cases happened in the past are presumably sporadic, but it is still possible that some isolates with strong virulence potential have caused listeriosis outbreaks, and future listeriosis risks also exist. PMID:25826318

  13. The first genetically confirmed Japanese patient with mucolipidosis type IV.

    PubMed

    Saijo, Harumi; Hayashi, Masaharu; Ezoe, Takanori; Ohba, Chihiro; Saitsu, Hirotomo; Kurata, Kiyoko; Matsumoto, Naomichi

    2016-05-01

    Mucolipidosis type IV (MLIV) is a rare neurodegenerative disorder characterized by severe psychomotor delay and visual impairment. We report the brain pathology in the first Japanese patient of MLIV with a novel homozygous missense mutation in MCOLN1. We detected the localized increase in p62-reactive astrocytes in the basal ganglia. PMID:27190617

  14. Current antiplatelet therapy for Japanese patients with ST elevation acute myocardial infarction: J-AMI registry.

    PubMed

    Nakamura, Masato; Yamagishi, Masakazu; Ueno, Takafumi; Hara, Kazuhiro; Ishiwata, Sugao; Itoh, Tomonori; Hamanaka, Ichiro; Wakatsuki, Tetsuzo; Wakatsuki, Tetuszo; Sugano, Teruyasu; Kawai, Kazuya; Kimura, Takeshi

    2013-04-01

    Antiplatelet therapy could prevent stent thrombosis, but may be associated with an increased risk of bleeding. Recent studies have revealed that bleeding complications are relatively frequent in patients with acute coronary syndromes. Our aim was to describe the current status of antiplatelet therapy for Japanese patients with acute myocardial infarction (AMI). The Japan AMI (J-AMI) registry is a prospective observational study that has enrolled 2,030 consecutive patients with stent thrombosis elevation myocardial infarction (STEMI) admitted to 213 participating Japanese institutions. Current antiplatelet therapy for STEMI was assessed, and the occurrence of bleeding complications (based on GUSTO bleeding criteria) and stent thrombosis was also evaluated. Additionally, the clinical course after bleeding episodes was investigated. Percutaneous coronary intervention (PCI) was done in 97.2% of the patients, using a drug-eluting stent in 30% and a bare metal stent in 63% of PCI cases. A 300-mg loading dose of clopidogrel followed by its administration at 75 mg/day with aspirin was the current standard treatment for Japanese STEMI patients. In-hospital bleeding complications occurred in 1.9%, especially in patients with severe clinical features or a history of cerebrovascular disease. Moderate to severe bleeding complications were associated with 10 deaths. The in-hospital stent thrombosis (ST) rate was 1.47 %, and loading with clopidogrel prior to PCI was significantly less frequent in patients who developed ST (P < 0.001). In conclusion, the J-AMI registry revealed that severe symptoms of STEMI increased the risk of bleeding, while delay of clopidogrel loading was associated with ST. These findings suggest the need for treatment based on risk stratification to improve the balance between the beneficial and adverse effects of antiplatelet therapy in Japanese STEMI patients. PMID:23233418

  15. 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. PMID:16054582

  16. Genotype-phenotype relationship in Japanese patients with congenital central hypoventilation syndrome.

    PubMed

    Shimokaze, Tomoyuki; Sasaki, Ayako; Meguro, Toru; Hasegawa, Hisaya; Hiraku, Yuka; Yoshikawa, Tetsushi; Kishikawa, Yumiko; Hayasaka, Kiyoshi

    2015-09-01

    Examine the genotype-phenotype relationship in Japanese congenital central hypoventilation syndrome (CCHS) patients and estimate the incidence of CCHS in Japan. Subjects were 92 Japanese patients with PHOX2B mutations; 19 cases carried 25 polyalanine repeat expansion mutations (PARMs); 67 cases carried 26 or more PARMs; and 6 had non-PARMs (NPARMs). We collected clinical data in all patients and estimated the development or intelligent quotients only in the patients carrying 25 PARM. The estimated incidence of CCHS was greater than one case per 148 000 births. Polyhydramnios was observed in three cases. Twelve infants exhibited depressed respiration at birth. In 19 cases carrying 25 PARM, the male-to-female ratio was ~3, no cases had Hirschsprung disease; 7 cases (37%) developed hypoventilation after the neonatal period, and 8 cases (42%) had mental retardation. In other 73 cases carrying 26 or more PARMs or NPARMs, male-to-female ratio was equal; patients frequently complicated with Hirschsprung disease and constipation, and all patients presented with hypoventilation in the neonatal period. Clinical symptoms were severe in most patients carrying long PARMs and NPARMs. In 25 PARM, additional genetic and/or epigenetic factors were required for CCHS development and male sex is likely a predisposing factor. The patients carrying 25 PARM frequently had mental retardation likely because they were not able to receive appropriate ventilation support following a definitive diagnosis owing to subtle and or irregular hypoventilation. Molecular diagnosis provides a definitive diagnosis and enables to receive appropriate ventilator support. PMID:26063465

  17. 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. PMID:18793583

  18. HLA antigens in Japanese patients with myasthenia gravis.

    PubMed Central

    Matsuki, K; Juji, T; Tokunaga, K; Takamizawa, M; Maeda, H; Soda, M; Nomura, Y; Segawa, M

    1990-01-01

    HLA antigens in 104 Japanese patients and 41 families with myasthenia gravis (MG) were investigated. The frequencies of DR9 and DRw13 were significantly increased in the patients who developed MG before 3 yr of age. The DQw3 antigen was positive for all the patients that developed MG before 15 yr with only one exception. All the examined cases that developed MG before 3 yr (including this DQw3 negative patient) had the same DQA and DQB DNA restriction fragments. These HLA frequencies decreased as the age of onset increased, and no significant association was observed in adult-onset MG. No patients had B8, DR3, and DQw2. The relative risk was higher for the DR9/DRw13 heterozygotes (37.4) than for DR9 (16.4) or DRw13 (7.1) in the childhood-onset MG. Statistical analysis suggested that DR9 and DRw13 (or DQw1 and DQw3) act synergistically in the disease development. Family study revealed diverse DR9 haplotypes. The most frequent DRw13 haplotype was Bw44-BFF-C4A3B1-DRw13-DQw1, which may be evolutionarily related to the caucasian B8-DR3-DQw2 haplotype. These results showed that MG in early childhood in Japanese individuals is genetically different from that in adulthood and that in caucasians. Images PMID:1974553

  19. 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.

  20. 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. PMID:19363645

  1. Exome sequencing reveals a novel missense mutation in the KIAA0196 gene in a Japanese patient with SPG8.

    PubMed

    Ichinose, Yuta; Koh, Kishin; Fukumoto, Megumi; Yamashiro, Nobuo; Kobayashi, Fumikazu; Miwa, Michiaki; Nagasaka, Takamura; Shindo, Kazumasa; Ishiura, Hiroyuki; Tsuji, Shoji; Takiyama, Dr Yoshihisa

    2016-05-01

    Exome sequencing revealed a novel missense mutation (c.2152G>A, p.E713K) in the KIAA0196 gene in a Japanese patient with SPG8. To date, only 10 mutations in the KIAA0196 gene have been reported in the world. We describe the clinical and genetic findings in our patient with SPG8, which is a rare dominant hereditary spastic paraplegia. Notably, our patient showed mild upper limb ataxia, which is a relatively atypical symptom of SPG8. Thus, our patient showed a wide clinical spectrum of SPG8. PMID:26967522

  2. 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.

  3. 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.

  4. Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses.

    PubMed

    Ishiura, Hiroyuki; Takahashi, Yuji; Hayashi, Toshihiro; Saito, Kayoko; Furuya, Hirokazu; Watanabe, Mitsunori; Murata, Miho; Suzuki, Mikiya; Sugiura, Akira; Sawai, Setsu; Shibuya, Kazumoto; Ueda, Naohisa; Ichikawa, Yaeko; Kanazawa, Ichiro; Goto, Jun; Tsuji, Shoji

    2014-03-01

    Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and pyramidal weakness of lower limbs. Because >30 causative genes have been identified, screening of multiple genes is required for establishing molecular diagnosis of individual patients with HSP. To elucidate molecular epidemiology of HSP in the Japanese population, we have conducted mutational analyses of 16 causative genes of HSP (L1CAM, PLP1, ATL1, SPAST, CYP7B1, NIPA1, SPG7, KIAA0196, KIF5A, HSPD1, BSCL2, SPG11, SPG20, SPG21, REEP1 and ZFYVE27) using resequencing microarrays, array-based comparative genomic hybridization and Sanger sequencing. The mutational analysis of 129 Japanese patients revealed 49 mutations in 46 patients, 32 of which were novel. Molecular diagnosis was accomplished for 67.3% (33/49) of autosomal dominant HSP patients. Even among sporadic HSP patients, mutations were identified in 11.1% (7/63) of them. The present study elucidated the molecular epidemiology of HSP in the Japanese population and further broadened the mutational and clinical spectra of HSP. PMID:24451228

  5. 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. PMID:25817352

  6. Alteration in plasma glucose levels in Japanese encephalitis patients.

    PubMed

    Tandon, Apurva; Singh, Aditi; Atrishi, Ekta; Saxena, S K; Mathur, Asha

    2002-02-01

    A unique factor, human T cell hypoglycaemic factor (hTCHF), has been shown to produce hypoglycaemia during the convalescent stage in the plasma of patients with Japanese encephalitis virus (JEV) infection. The present study was undertaken to investigate the ability of T cells from fresh peripheral blood mononuclear cells (PBMC) of such patients to produce hTCHF. The PBMC, as well as the individual subpopulations, were cultured for 24 h and the culture supernatants (CS) were assayed for hypoglycaemic activity. The activity was observed in the CD8+ T cells. The hypoglycaemia in JE-confirmed patients coincided with the gradual rise in circulating glucagon level, with no significant alterations in insulin, growth hormone and cortisol levels. The hTCHF was purified by ion exchange chromatography and the purified protein was observed as a approximately 25 kDa band on SDS-PAGE. Secretory hTCHF in the sera of patients and T cell CS was present in 88% of convalescent serum samples. We conclude that during the convalescent stage of JEV infection, a unique factor, hTCHF, is secreted by activated CD8+ T cells from patients and that this is responsible for the development of hypoglycaemia. PMID:12059908

  7. Impact of obesity on the efficacy of ustekinumab in Japanese patients with psoriasis: a retrospective cohort study of 111 patients.

    PubMed

    Yanaba, Koichi; Umezawa, Yoshinori; Ito, Toshihiro; Hayashi, Mitsuha; Kikuchi, Sota; Fukuchi, Osamu; Saeki, Hidehisa; Nakagawa, Hidemi

    2014-12-01

    Obesity is thought to be involved in the pathogenesis of psoriasis, although its impact on the therapeutic response to systemic treatments remains unclear. The aim of this study was to examine the association of body mass index (BMI) with the efficacy of ustekinumab in Japanese patients with psoriasis. Clinical data from a cohort of 111 Japanese patients treated with ustekinumab 45 mg between July 2011 and March 2014 were retrospectively evaluated. The measured outcome was improvement in the psoriasis area and severity index (PASI) score at week 16. Patients with BMI ≥ 25 and BMI < 25 had comparable rates of ≥50 and 75 % improvement in PASI (PASI-50 and PASI-75, respectively), whereas patients with BMI ≥ 25 had significantly lower PASI-90 and PASI-100 response rates. Patients with BMI ≥ 25 also showed significantly lower percent reduction in PASI than those with BMI < 25 at week 16 (85 vs. 74 %, P < 0.004). BMI was negatively correlated with percent reduction in PASI, whereas body weight was not. These results show that a higher BMI, but not body weight, is associated with lower effectiveness of ustekinumab for psoriasis. BMI ≥ 25 could therefore be a negative predictor of achieving PASI-90 and PASI-100 in patients with psoriasis when starting ustekinumab. PMID:25193345

  8. Japanese version of the Dermatology Life Quality Index: validity and reliability in patients with acne

    PubMed Central

    Takahashi, Natsuko; Suzukamo, Yoshimi; Nakamura, Motonobu; Miyachi, Yoshiki; Green, Joseph; Ohya, Yukihiro; Finlay, Andrew Y; Fukuhara, Shunichi

    2006-01-01

    Background Patient-reported quality of life is strongly affected by some dermatologic conditions. We developed a Japanese version of the Dermatology Life Quality Index (DLQI-J) and used psychometric methods to examine its validity and reliability. Methods The Japanese version of the DLQI was created from the original (English) version, using a standard method. The DLQI-J was then completed by 197 people, to examine its validity and reliability. Some participants completed the DLQI-J a second time, 3 days later, to examine the reproducibility of their responses. In addition to the DLQI-J, the participants completed parts of the SF-36 and gave data on their demographic and clinical characteristics. Their physicians provided information on the location and clinical severity of the skin disease. Results The participants reported no difficulties in answering the DLQI-J items. Their mean age was 24.8 years, 77.2% were female, and 78.7% had acne vulgaris. The mean score of DLQI was 3.99(SD: 3.99). The responses were found to be reproducible and stable. Results of principal-component and factor analysis suggested that this scale measured one construct. The correlations of DLQI-J scores with sex or age were very poor, but those with SF-36 scores and with clinical severity were high. Conclusion The DLQI-J provides valid and reliable data despite having only a small number of items. PMID:16884543

  9. Efficacy and safety of monotherapy by pegvisomant, a growth hormone receptor antagonist, in Japanese patients with acromegaly.

    PubMed

    Shimatsu, Akira; Nagashima, Masahito; Hashigaki, Satoshi; Ohki, Nobuhiko; Chihara, Kazuo

    2016-04-25

    Pegvisomant is a GH receptor antagonist and strong inhibitor of insulin-like growth factor I (IGF-I) production. The treatment goal for acromegaly is to normalize serum IGF-I levels and attenuate associated symptoms. The efficacy and safety of pegvisomant as treatment for acromegaly have been reported in Caucasians, but not in Japanese. Here we report the clinical experience of using pegvisomant in Japanese patients with acromegaly. The efficacy and safety data for pegvisomant from two open-labeled clinical studies in Japan, conducted from 2004 to 2007, were re-analyzed using the new Japanese age- and sex-matched normative ranges for IGF-I. Eighteen patients with active acromegaly were enrolled in an initial pivotal study, and 16 of them were moved to a long-term (max 168 weeks) extension study. The dose of pegvisomant in the extension study was adjusted to 10-30 mg per day according to IGF-I levels. IGF-I normalization was observed in 81.3% (13/16 patients) during the extension study. The mean percentage decrease from baseline in serum IGF-I level was 64.7% at the time of last observation. The clinical symptoms and overall health status were improved, and the ring size was reduced over time until Week 12 and maintained. For safety, no clinically significant changes were observed both in the pituitary tumor size and the anti-GH antibody level. Three subjects were withdrawn from the studies due to an abnormal elevation of liver enzymes which resolved after discontinuation. Pegvisomant demonstrated excellent clinical efficacy and was well tolerated in Japanese patients with acromegaly. PMID:26796763

  10. [Effects of drug adherence on patient outcomes to early treatment for Japanese cedar pollinosis].

    PubMed

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

    2004-07-01

    Drug adherence is one of the important aspects in caring for patients with allergic rhinitis. To improve clinical efficacy of early treatment for Japanese cedar pollinosis (JCP), we evaluated the effect of drug adherence on patients' outcomes. Patients were randomly selected from 16 ENT clinical sites in Osaka and Wakayama between February 24 and March 8, 2003 (peak pollen season). Efficacy was assessed using patients' ratings of nasal and ocular symptoms and overall assessment in their condition compared with previous season ones. Costs include direct costs of the drugs used for treatment to JCP from January to February. Five hundred one patients taking early treatment were enrolled. Compared to low adherence patients, those who reported higher level of adherence significantly improved overall health condition, and achieved better symptom relief of rhinorrhea and nasal congestion. In multiple logistic regression analysis, the following factors were independent risk factors for low adherence: student (p=0.002), using OTC medications (p=0.006), and short-duration of medication (p=0.001). Low costs were also risk factor for low adherence. We conclude that taking medications for JCP for 22-28 days is the best way to enhance patients' outcomes. PMID:15492491

  11. 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

  12. Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus

    PubMed Central

    Yamada, Masanori; Akita, Mikio; Nakagawa, Tomofumi; Takahashi, Naoki; Endo, Akira; Yoshida, Pascal

    2013-01-01

    Objectives Belimumab, an anti-B lymphocyte stimulator (BLyS) human monoclonal antibody, was approved in the United States, Canada and European Union for the treatment of the patients with systemic lupus erythematosus (SLE). However, belimumab had not been evaluated in Japanese patients. The objectives of this study were to evaluate the safety and tolerability of belimumab in Japanese patients with SLE, as well as to investigate the pharmacokinetics (PK) and biological activity of belimumab in this population. Methods A total of 12 Japanese patients were enrolled in a randomized, single-blind, placebo-controlled, dose-ascending design study. A dosing regimen of a single intravenous infusion over 1 hour of belimumab (1 mg/kg and 10 mg/kg) was employed. Patients were followed for 84 days after dosing to assess adverse events, pharmacokinetics, biomarkers and SLE disease activity. Clinical trial registration number ClinicalTrials.gov identifier is NCT01381536. Results Belimumab (1 mg/kg and 10 mg/kg) demonstrated a favorable clinical safety and tolerability profile in Japanese patients with SLE. The incidence of adverse events was similar among the two belimumab groups and placebo group. The PK profile of single-dose belimumab was approximately dose proportional, and the long terminal elimination half-life (12.4–15.7 days), low clearance (3.55–4.65 mL/day/kg), and small volume of distribution (76.2–80.1 mL/kg) were consistent with a fully humanized antibody. Effects of belimumab on B cells suggested biological activity effects expected as an inhibitor of BLyS. Limitation The small sample size and single dose design of this study prevent definitive conclusions regarding the safety, pharmacokinetics or pharmacodynamics of belimumab in a Japanese population being made. Conclusions The preliminary safety, PK profile, and observed biological activity of belimumab support further evaluation of its safety and efficacy in Japanese patient with SLE.

  13. Postmarketing surveillance of the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis

    PubMed Central

    Harigai, Masayoshi; Ishiguro, Naoki; Inokuma, Shigeko; Mimori, Tsuneyo; Ryu, Junnosuke; Takei, Syuji; Takeuchi, Tsutomu; Tanaka, Yoshiya; Takasaki, Yoshinari; Yamanaka, Hisashi; Watanabe, Masahiko; Tamada, Hiroshi; Koike, Takao

    2016-01-01

    Abstract Objective: To perform a postmarketing surveillance study evaluating the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis (RA). Methods: Safety and effectiveness data were collected for all RA patients (at 772 sites) treated with intravenous abatacept between September 2010 and June 2011. Patients were treated by the approved dosing regimen according to the package insert. Treatment effectiveness was evaluated at baseline and at weeks 4, 12, and 24 using Disease Activity Score 28 (DAS28) according to erythrocyte sedimentation rate or serum C-reactive protein concentrations. Results: Overall, 3882 and 3016 abatacept-naïve RA patients were included in safety and effectiveness analyses, respectively. Adverse drug reactions (ADRs) were reported for 15.66% of patients and serious ADRs were detected for 2.52% of patients. The incidence of serious infections was 1.03% and these were mainly attributed to different types of bacterial pneumonia. Disease activity improved significantly over 6 months. Separate multivariate analysis identified predictors of severe ADR, and severe infections and factors predictive of clinically meaningful DAS28 improvement after 6 months of treatment with abatacept. Conclusions: Abatacept was efficacious and well tolerated in a clinical setting. No new safety concerns were detected. PMID:26635183

  14. 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. PMID:26984589

  15. Epidemiological analysis of prognosis of 496 Japanese patients with progressive systemic sclerosis (SSc). Scleroderma Research Committee Japan.

    PubMed

    Nishioka, K; Katayama, I; Kondo, H; Shinkai, H; Ueki, H; Tamaki, K; Takehara, K; Tajima, S; Maeda, M; Hayashi, S; Kodama, H; Miyachi, Y; Mizutani, H; Fujisaku, A; Sasaki, T; Shimizu, M; Kaburagi, J

    1996-10-01

    For the first time, we performed an epidemiological study of SSc in Japan to study the factors influencing prognosis, survival rate and cause of death of Japanese SSc patients and to compare our data with those from foreign countries. Prognosis of 496 Japanese patients with progressive systemic sclerosis (SSc) was analyzed based on clinical data described in case cards provided by the members of the Scleroderma Research Committee of the Japanese Ministry of Health and Welfare. The essential observation period was from 5 to 20 years, at ending in 1994. Ninety patients died (males 11, females 79). The age of onset of the deceased patients was significantly higher than that of surviving patients (deceased, 45.6 yrs, surviving 41.3 yrs). Statistically significant factors for a poor prognosis were as follows: Barnett type III > type II > type I, positive for anti-Scl-70 antibody, negative for anti-centromere antibody. The survival rate at 5 years after the onset of the disease was 0.937, followed by 0.82 at 10 years, 0.567 at 20 years and 0.40 at 30 years after the onset. Sex was not a predictor for prognosis, although male patients died at an earlier stage of the disease. The most common causes of death were heart failure, pulmonary insufficiency, lung fibrosis, and renal failure. Twenty-four patients had cancer of which 13 were lung cancers. The current status of the survival rate and prognostic factors of 496 Japanese SSc patients is summarized. In future, more well-controlled studies using the same criteria should be performed for the better understanding and management of SSc. PMID:8973032

  16. 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. PMID:27545002

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

    PubMed Central

    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. PMID:26870359

  18. Pharmacokinetics and safety of voriconazole intravenous-to-oral switch regimens in immunocompromised Japanese pediatric patients.

    PubMed

    Mori, Masaaki; Kobayashi, Ryoji; Kato, Koji; Maeda, Naoko; Fukushima, Keitaro; Goto, Hiroaki; Inoue, Masami; Muto, Chieko; Okayama, Akifumi; Watanabe, Kenichi; Liu, Ping

    2015-02-01

    The aim of this study was to investigate the pharmacokinetics, safety, and tolerability of voriconazole following intravenous-to-oral switch regimens used with immunocompromised Japanese pediatric subjects (age 2 to <15 years) at high risk for systemic fungal infection. Twenty-one patients received intravenous-to-oral switch regimens based on a recent population pharmacokinetic modeling; they were given 9 mg/kg of body weight followed by 8 mg/kg of intravenous (i.v.) voriconazole every 12 h (q12h), and 9 mg/kg (maximum, 350 mg) of oral voriconazole q12h (for patients age 2 to <12 or 12 to <15 years and <50 kg) or 6 mg/kg followed by 4 mg/kg of i.v. voriconazole q12h and 200 mg of oral voriconazole q12h (for patients age 12 to <15 years and ≥50 kg). The steady-state area under the curve over the 12-h dosing interval (AUC0-12,ss) was calculated using the noncompartmental method and compared with the predicted exposures in Western pediatric subjects based on the abovementioned modeling. The geometric mean (coefficient of variation) AUC0-12,ss values for the intravenous and oral regimens were 51.1 μg · h/ml (68%) and 45.8 μg·h/ml (90%), respectively; there was a high correlation between AUC0-12,ss and trough concentration. Although the average exposures were higher in the Japanese patients than those in the Western pediatric subjects, the overall voriconazole exposures were comparable between these two groups due to large interindividual variability. The exposures in the 2 cytochrome P450 2C19 poor metabolizers were among the highest. Voriconazole was well tolerated. The most common treatment-related adverse events were photophobia and abnormal hepatic function. These recommended doses derived from the modeling appear to be appropriate for Japanese pediatric patients, showing no additional safety risks compared to those with adult patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01383993.). PMID:25451051

  19. 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

  20. 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

  1. Long-term (52 weeks) safety and tolerability of umeclidinium in Japanese patients with chronic obstructive pulmonary disease.

    PubMed

    Yamagata, Eiji; Soutome, Toru; Hashimoto, Kenichi; Mihara, Kazuko; Tohda, Yuji

    2016-05-01

    Objective Umeclidinium bromide (UMEC) 62.5 μg is a long-acting muscarinic antagonist (LAMA) that is administered once daily via inhalation for chronic obstructive pulmonary disease (COPD) treatment. The objective of this study was to evaluate the safety and tolerability of long-term treatment with UMEC 125 μg in Japanese patients with COPD. Methods This was a 52 week, multicenter, open-label study to evaluate the safety and tolerability of UMEC 125 μg once daily delivered via a novel dry powder inhaler (nDPI) in Japanese patients with COPD. The primary endpoint was the incidence and severity of all adverse events (AEs) throughout the 52 week treatment period. Clinical trial registration number ClinicalTrials.gov identifier is NCT01702363. Results A total of 153 patients were enrolled in the study. Of these, 131 patients started treatment with UMEC 125 μg, and 111 patients (85%) completed the study. AEs did not differ greatly in incidence over the various time periods (Weeks 0 to 12, 13 to 24, 25 to 36, and 37 to 52 of treatment) and did not increase with continued treatment. The incidence of drug-related AEs associated with the pharmacological effects of LAMAs (including constipation, blurred vision, and thirst) was low. Serious adverse events (SAEs) during the treatment period were reported in 17 patients (13%). SAEs reported in more than one patient were COPD exacerbation and pneumonia (3 patients each, 2%). One SAE of angina pectoris was considered to be drug related. No fatalities were reported during this study. Conclusions No new AEs were identified beyond those attributable to the pharmacological effects of LAMAs. UMEC 125 μg was well tolerated over 52 weeks of treatment in Japanese patients with COPD. PMID:26782971

  2. Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma.

    PubMed

    Yamashita, Hideomi; Onishi, Hiroshi; Murakami, Naoya; Matsumoto, Yasuo; Matsuo, Yukinori; Nomiya, Takuma; Nakagawa, Keiichi

    2015-05-01

    Stereotactic body radiotherapy (SBRT) is a relatively new treatment for liver tumor. Outcomes of SBRT for liver tumors unsuitable for ablation or surgical resection were evaluated. A total of 79 patients treated with SBRT for primary hepatocellular carcinoma (HCC) between 2004 and 2012 in six Japanese institutions were studied retrospectively. Patients treated with SBRT preceded by trans-arterial chemoembolization were eligible. Their median age was 73 years, 76% were males, and their Child-Pugh scores were Grades A (85%) and B (11%) before SBRT. The median biologically effective dose (α/β = 10 Gy) was 96.3 Gy. The median follow-up time was 21.0 months for surviving patients. The 2-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival were 53%, 40% and 76%, respectively. Sex and serum PIVKA-II values were significant predictive factors for OS. Hypovascular or hypervascular types of HCC, sex and clinical stage were significant predictive factors for PFS. The 2-year PFS was 66% in Stage I vs 18% in Stages II-III. Multivariate analysis indicated that clinical stage was the only significant predictive factor for PFS. No Grade 3 laboratory toxicities in the acute, sub-acute, and chronic phases were observed. PFS after SBRT for liver tumor was satisfactory, especially for Stage I HCC, even though these patients were unsuitable for resection and ablation. SBRT is safe and might be an alternative to resection and ablation. PMID:25691453

  3. Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma

    PubMed Central

    Yamashita, Hideomi; Onishi, Hiroshi; Murakami, Naoya; Matsumoto, Yasuo; Matsuo, Yukinori; Nomiya, Takuma; Nakagawa, Keiichi

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is a relatively new treatment for liver tumor. Outcomes of SBRT for liver tumors unsuitable for ablation or surgical resection were evaluated. A total of 79 patients treated with SBRT for primary hepatocellular carcinoma (HCC) between 2004 and 2012 in six Japanese institutions were studied retrospectively. Patients treated with SBRT preceded by trans-arterial chemoembolization were eligible. Their median age was 73 years, 76% were males, and their Child–Pugh scores were Grades A (85%) and B (11%) before SBRT. The median biologically effective dose (α/β = 10 Gy) was 96.3 Gy. The median follow-up time was 21.0 months for surviving patients. The 2-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival were 53%, 40% and 76%, respectively. Sex and serum PIVKA-II values were significant predictive factors for OS. Hypovascular or hypervascular types of HCC, sex and clinical stage were significant predictive factors for PFS. The 2-year PFS was 66% in Stage I vs 18% in Stages II–III. Multivariate analysis indicated that clinical stage was the only significant predictive factor for PFS. No Grade 3 laboratory toxicities in the acute, sub-acute, and chronic phases were observed. PFS after SBRT for liver tumor was satisfactory, especially for Stage I HCC, even though these patients were unsuitable for resection and ablation. SBRT is safe and might be an alternative to resection and ablation. PMID:25691453

  4. 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

  5. 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. PMID:27305898

  6. 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. PMID:21254867

  7. 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

  8. A multicenter cross-sectional study of circulating soluble urokinase receptor in Japanese patients with glomerular disease.

    PubMed

    Wada, Takehiko; Nangaku, Masaomi; Maruyama, Shoichi; Imai, Enyu; Shoji, Kumi; Kato, Sawako; Endo, Tomomi; Muso, Eri; Kamata, Kouju; Yokoyama, Hitoshi; Fujimoto, Keiji; Obata, Yoko; Nishino, Tomoya; Kato, Hideki; Uchida, Shunya; Sasatomi, Yoshie; Saito, Takao; Matsuo, Seiichi

    2014-03-01

    Elevated serum-soluble urokinase receptor (suPAR) levels have been described in patients with focal segmental glomerulosclerosis (FSGS) in several different cohorts. However, it remains unclear whether this is the case for Japanese patients and whether circulating suPAR can be clinically useful as a diagnostic marker. To determine this, we measured serum suPAR levels in 69 Japanese patients with biopsy-proven glomerular diseases in a cross-sectional manner. The serum suPAR levels showed a significant inverse correlation with renal function by univariate (R(2) of 0.242) and multivariate (β=0.226) analyses. Even after excluding patients with renal dysfunction, no significant difference in the suPAR levels was detected among the groups. Receiver operating characteristic analysis and measures of the diagnostic test performance showed that suPAR was not a useful parameter for differentiating FSGS from the other glomerular diseases (AUC-ROC: 0.621), although a small subgroup analysis showed that patients with FSGS, treated with steroids and/or immunosuppressants, had significantly lower suPAR levels. Patients with ANCA-associated glomerulonephritis had significantly higher levels of suPAR compared with the other disease groups, which may be owing to their lower renal function and systemic inflammation. Thus, suPAR levels are significantly affected by renal function and have little diagnostic value even in patients with normal renal function. PMID:24429394

  9. 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…

  10. Effects of cigarette smoking and cytochrome P450 2D6 genotype on fluvoxamine concentration in plasma of Japanese patients.

    PubMed

    Katoh, Yasuhiro; Uchida, Shinya; Kawai, Masayoshi; Takei, Noriyoshi; Mori, Norio; Kawakami, Junichi; Kagawa, Yoshiyuki; Yamada, Shizuo; Namiki, Noriyuki; Hashimoto, Hisakuni

    2010-01-01

    Fluvoxamine is a selective serotonin reuptake inhibitor widely used in the treatment of depression and other psychiatric diseases. The aim of this study was to assess the clinical impact of cigarette smoking on plasma fluvoxamine concentration in Japanese patients, and evaluate whether the cytochrome P450 (CYP) 1A2 and CYP2D6 genotypes have effects on that concentration. Thirty-two Japanese patients receiving fluvoxamine were enrolled. They were maintained on the same daily dose of fluvoxamine (mean + or - S.D., 109.4 + or - 66.2 mg/d) for at least 4 weeks to obtain the steady-state plasma concentration. The steady-state plasma concentration-to-dose (C/D) ratio of fluvoxamine in patients who smoked (n = 6, 11.8 + or - 6.5 ng/ml/dose) was significantly lower than that in non-smoker patients (n = 26, 22.8 + or - 11.2 ng/ml/dose). There was no significant difference for the C/D ratio of fluvoxamine in patients with CYP1A2 -3860G/G, -3860G/A, and -3860A/A between non-smokers and smokers. Among non-smoker patients, the C/D ratios of fluvoxamine in those with one and two mutated alleles of CYP2D6 were 1.6- and 1.4-fold higher, respectively, than those with no mutated alleles, though the differences among those three genotype groups were not significant. Furthermore, stepwise multiple regression analysis revealed that cigarette smoking and daily dose had significant positive correlations with the plasma concentration of fluvoxamine. Our findings suggest that cigarette smoking has a significant impact on the steady-state plasma concentration of fluvoxamine in Japanese patients. PMID:20118554

  11. 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

  12. HIV-associated Burkitt lymphoma in a Japanese patient with early submandibular swelling

    PubMed Central

    2013-01-01

    Background Patients infected with the human immunodeficiency virus (HIV) are at risk of developing malignancies and have an increased susceptibility to infection. HIV-associated Burkitt lymphoma (BL) is relatively rare in developed countries, but remains prevalent in developing counties and is sometimes compounded by the fact that patients may be unaware that they are HIV-positive. Case presentation A 37-year-old Japanese man was referred to our department for diagnosis and management of submandibular swelling. He was unaware that he was HIV-positive at the initial visit. Here, we describe our diagnostic approach, in which we used hematological and immunological investigations, biopsy, fluorescence-activated cell sorting and fluorescence in situ hybridization to confirm the diagnosis of HIV-associated BL. The patient has no risk factors for HIV infection, and the source of infection remains unclear. Conclusions In this case, submandibular swelling was the first clinical sign of pathology and the patient’s HIV-positive status only became evident later. It is highly likely that BL was triggered by HIV infection. PMID:24370065

  13. Revisiting Shimoda's “Shuuchaku-Kishitsu” (Statothymia): A Japanese View of Manic-Depressive Patients

    PubMed Central

    Tsuda, Hitoshi

    2011-01-01

    Although the empiric paradigm is now dominant in academic research, in Japan quite a few psychiatric clinicians still take phenomenological-anthropological approaches into consideration, especially when they address manic-depressive illness with typical endogenous features. This is because Shimoda's concept of “shuuchaku-kishitsu” (statothymia) has been widely accepted, together with other phenomenological views of continental origin. In the present paper the author first delineates Shimoda's concept which is based on observations of patients' personality features and the characteristics of their emotionality. He then attempts to refine this concept in spatiotemporal terms, presenting the view that in patients the past self tends to adhere to the present self (the term “shuuchaku” means “adhering to” or “preoccupied with”). He also considers that patients tend to incorporate “soto” (outer space) into “uchi” (inner space), where they believe that symbiotic relations are preserved. Finally, he argues the clinical significance of the presented views in the cultural milieu in which Japanese psychiatric practices are situated. PMID:21941642

  14. 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. PMID:21523338

  15. Humoral response against host-mimetic homologous epitopes of Mycobacterium avium subsp. paratuberculosis in Japanese multiple sclerosis patients

    PubMed Central

    Cossu, Davide; Yokoyama, Kazumasa; Sechi, Leonardo Antonio; Otsubo, Shigeru; Tomizawa, Yuji; Momotani, Eiichi; Hattori, Nobutaka

    2016-01-01

    Several works have demonstrated the existence of a link between Mycobacterium avium subsp. paratuberculosis (MAP) and MS in Italy. In this study, we analyzed the serology of MAP in a Japanese population while looking at several markers of MAP. Fifty MS patients, 12 clinically isolated syndrome (CIS) patients, 30 other neurological disorders (OND) patients, and 50 healthy controls (HCs) were tested using ELISA for the presence of IgG antibodies toward immunodominant epitopes MAP_0106c121-132, homologues MBP85-98, homologues IRF5424-432, MAP_402718-32, and MAP_2694295-303. MAP-positive patients were also analyzed in relation to their clinical/demographic characteristics. Amongst all peptides, only antibodies against MAP_2694295-303 were more prevalent in MS patients (30%), as compared to OND patients (3%) (p = 0.009; area under roc curve (AUC) = 0.61) and HCs (2%) (p = 0.0004; AUC = 0.65) and in CIS patients (25%) compared to HCs (p = 0.023; AUC = 0.55). Logistic regression analysis showed a higher frequency of anti-MAP_2694295-303 antibodies in the sera of oligoclonal bands positive MS patients (p = 0.2; OR = 2, 95%CI: 0.55–7.7). These findings support the view that MAP could act as a risk factor or a triggering agent of MS in some Japanese patients with a genetic susceptibility to the mycobacterium. PMID:27356622

  16. Humoral response against host-mimetic homologous epitopes of Mycobacterium avium subsp. paratuberculosis in Japanese multiple sclerosis patients.

    PubMed

    Cossu, Davide; Yokoyama, Kazumasa; Sechi, Leonardo Antonio; Otsubo, Shigeru; Tomizawa, Yuji; Momotani, Eiichi; Hattori, Nobutaka

    2016-01-01

    Several works have demonstrated the existence of a link between Mycobacterium avium subsp. paratuberculosis (MAP) and MS in Italy. In this study, we analyzed the serology of MAP in a Japanese population while looking at several markers of MAP. Fifty MS patients, 12 clinically isolated syndrome (CIS) patients, 30 other neurological disorders (OND) patients, and 50 healthy controls (HCs) were tested using ELISA for the presence of IgG antibodies toward immunodominant epitopes MAP_0106c121-132, homologues MBP85-98, homologues IRF5424-432, MAP_402718-32, and MAP_2694295-303. MAP-positive patients were also analyzed in relation to their clinical/demographic characteristics. Amongst all peptides, only antibodies against MAP_2694295-303 were more prevalent in MS patients (30%), as compared to OND patients (3%) (p = 0.009; area under roc curve (AUC) = 0.61) and HCs (2%) (p = 0.0004; AUC = 0.65) and in CIS patients (25%) compared to HCs (p = 0.023; AUC = 0.55). Logistic regression analysis showed a higher frequency of anti-MAP_2694295-303 antibodies in the sera of oligoclonal bands positive MS patients (p = 0.2; OR = 2, 95%CI: 0.55-7.7). These findings support the view that MAP could act as a risk factor or a triggering agent of MS in some Japanese patients with a genetic susceptibility to the mycobacterium. PMID:27356622

  17. Pattern reversal visual evoked potentials in Japanese patients with multiple sclerosis.

    PubMed Central

    Shibasaki, H; Kuroiwa, Y

    1982-01-01

    Forty-seven Japanese patients with multiple sclerosis, 29 probable (clinically definite) and 18 possible, were studied by black-and-white checkerboard pattern reversal visual evoked potential and were compared with a control group of 20 healthy young adults. The major positive peak (P100) was found to be abnormal in 70% of all cases, 90% of probable cases and 39% of possible cases. P100 was delayed in 38% of all cases and was absent in 23% of all cases. None of the eyes showing a flat pattern response was in the acute stage of optic neuritis. The percentage of cases with no response (23% of all cases) was greater than any of the previously reported series from Western countries, substantiating the previously reported clinical features of oriental multiple sclerosis. The pattern response was absent only when testing eyes with severe visual impairment, whereas delayed latency of P100 was seen regardless of the severity of visual impairment, suggesting the usefulness of P100 latency for detecting subclinical optic nerve lesions. PMID:7161609

  18. Pomalidomide alone or in combination with dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma.

    PubMed

    Matsue, Kosei; Iwasaki, Hiromi; Chou, Takaaki; Tobinai, Kensei; Sunami, Kazutaka; Ogawa, Yoshiaki; Kurihara, Mari; Midorikawa, Shuichi; Zaki, Mohamed; Doerr, Thomas; Iida, Shinsuke

    2015-11-01

    This phase 1, open-label, dose-escalation study investigated the tolerated dose (recommended dose), safety, efficacy, and pharmacokinetics of pomalidomide alone or pomalidomide plus low-dose dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma. Twelve patients were enrolled. Patients received pomalidomide 2 mg (Cohort 1) or 4 mg (Cohort 2) orally on day 1 and days 3-21 of a 28-day cycle. The tolerated dose of pomalidomide was determined to be 4 mg given on days 1-21 of a 28-day cycle. Efficacy outcomes with pomalidomide plus low-dose dexamethasone were consistent with those of previous studies. Responses (partial response or better) were achieved by three patients (25%; 1 [17%] in Cohort 1 and 2 [33%] in Cohort 2), and the median time to response was 6.4 months overall (9.0 months for Cohort 1 and 4.2 months for Cohort 2). The median progression-free survival was 5.5 months overall (5.1 months for Cohort 1 and not reached for Cohort 2). The most frequently occurring grade ≥3 adverse events were neutropenia (67%), anemia (25%), lymphopenia (25%), and pneumonia (25%), consistent with previous studies of pomalidomide plus low-dose dexamethasone in refractory or relapsed and refractory multiple myeloma. Further investigation of pomalidomide is recommended for Japanese patients with refractory or relapsed and refractory multiple myeloma. This study was registered with ClinicalTrials.gov (NCT01568294). PMID:26292221

  19. 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

  20. 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

  1. 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. PMID:25989891

  2. Efficacy and safety of insulin degludec in Japanese patients with type 1 and type 2 diabetes: 24-week results from the observational study in routine clinical practice.

    PubMed

    Kobuke, Kazuhiro; Yoneda, Masayasu; Nakanishi, Shuhei; Ohno, Haruya; Maeda, Shusaku; Egusa, Genshi

    2016-01-01

    This is first observational prospective study of insulin degludec in routine clinical practice that we evaluated the effect on glycemic control and risk of hypoglycemia in basal-bolus insulin therapy. We found that insulin degludec can maintain glycemic control at a lower insulin dose and frequency of hypoglycemia in type 1 diabetes, while it can improve glycemic control at equally insulin dose in type 2 diabetes. These results mean that insulin degludec is of use in routine clinical practice. PMID:26816606

  3. [Skin collagen abnormalities in a Japanese patient with extracranial internal carotid artery dissection followed by extracranial vertebral artery dissection].

    PubMed

    Sengoku, Renpei; Sato, Hironori; Honda, Hidehiko; Inoue, Kiyoharu; Ono, Seiitsu

    2006-02-01

    A 41-year-old man with hypertension and hyperlipidemia who complained of left hemiparesis after a temporal headache was admitted to our hospital. A cervical MRI with gadolinium enhancement revealed an intramural hematoma is compatible with right extracranial internal carotid artery dissection. Two weeks later, he complained of sudden onset of pain in the right side of his neck. The right extracranial internal carotid artery dissection followed by the right extracranial vertebral artery dissection was diagnosed. Spontaneous cervical artery dissection (SCAD) is one of the causes of stroke in young adults. The pathogenesis of SCAD remains unknown. Minor trauma like an excessive sneeze, migraine, and connective tissue disorders such as fibromuscular dysplasia and Ehlers-Danlos syndrome are well-known as risk factors for SCAD. Pathologically skin collagen abnormalities have been seen in German patients with SCAD without clinical evidence for any specific connective tissue disorder. We examined the ultrastructural morphology of the Japanese patient's dermal connective tissue components by electron microscopy. The patient's collagen fibers contained fibrils with highly variable diameters, and there were other ultrastructural abnormalities, including flower-like fibrils and large-diameter composite fibrils. This is the first report of a case of ultrastructural abnormalities of dermal connective tissue in a Japanese patient with SCAD. PMID:16619839

  4. 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

  5. BRAF V600 mutations and pathological features in Japanese melanoma patients

    PubMed Central

    Tanaka, Ryota; Tsutsumida, Arata; Namikawa, Kenjiro; Eguchi, Hironobu; Omata, Wataru; Oashi, Kohei; Ogawa, Toru; Hayashi, Amiko; Nakamura, Noriyuki; Tsuta, Koji

    2015-01-01

    Ultraviolet radiation is a risk factor for BRAF V600 mutations frequently found in melanomas that cause constitutive BRAF activation. Primary sites of melanoma and the frequency of BRAF mutations might differ between races. Melanoma is rare in Japan (1500–2000 cases/year compared with 132 000/year worldwide) and the frequency and distribution of BRAF V600 mutations are unknown. We aimed to investigate the frequency of BRAF V600 mutations in a cohort of Japanese patients with melanoma and determine the relationship between mutations and clinical/pathologic features. DNA was extracted from 80 formalin-fixed, paraffin-embedded tumours from individuals diagnosed with melanoma. BRAF V600 mutations were detected using the Cobas 4800 System with z480 Analyzer and Cobas 4800 BRAF V600 Mutation Test reagents. BRAF V600 mutations were detected in 41.8% of tested tumours, with an invalid rate of 1.3%. The mutation rate was more than 60% in patients aged less than 60 years and more than 36% in patients with stage III/IV disease. No sex difference in the mutation rate was observed. BRAF V600 mutations were detected in 18.8% of acral lentiginous melanomas (ALMs), 64.7% of superficial spreading melanomas, 50.0% of lentigo maligna melanomas and 20.0% of nodular melanomas. Although the mutation rate was low in ALMs, 36.4% were mutation positive at stage III/IV compared with 9.5% at stage I/II. This study confirmed associations among BRAF V600 mutations, pathological features and subtypes of melanoma. BRAF V600 mutations were more frequent in late-stage ALMs than in early-stage ALMs. Superficial spreading melanomas had similar mutation rates at all stages. These insights suggest improved treatment predictions for stage III/IV melanoma patients. PMID:25051202

  6. BRAF V600 mutations and pathological features in Japanese melanoma patients.

    PubMed

    Yamazaki, Naoya; Tanaka, Ryota; Tsutsumida, Arata; Namikawa, Kenjiro; Eguchi, Hironobu; Omata, Wataru; Oashi, Kohei; Ogawa, Toru; Hayashi, Amiko; Nakamura, Noriyuki; Tsuta, Koji

    2015-02-01

    Ultraviolet radiation is a risk factor for BRAF V600 mutations frequently found in melanomas that cause constitutive BRAF activation. Primary sites of melanoma and the frequency of BRAF mutations might differ between races. Melanoma is rare in Japan (1500-2000 cases/year compared with 132 000/year worldwide) and the frequency and distribution of BRAF V600 mutations are unknown. We aimed to investigate the frequency of BRAF V600 mutations in a cohort of Japanese patients with melanoma and determine the relationship between mutations and clinical/pathologic features. DNA was extracted from 80 formalin-fixed, paraffin-embedded tumours from individuals diagnosed with melanoma. BRAF V600 mutations were detected using the Cobas 4800 System with z480 Analyzer and Cobas 4800 BRAF V600 Mutation Test reagents. BRAF V600 mutations were detected in 41.8% of tested tumours, with an invalid rate of 1.3%. The mutation rate was more than 60% in patients aged less than 60 years and more than 36% in patients with stage III/IV disease. No sex difference in the mutation rate was observed. BRAF V600 mutations were detected in 18.8% of acral lentiginous melanomas (ALMs), 64.7% of superficial spreading melanomas, 50.0% of lentigo maligna melanomas and 20.0% of nodular melanomas. Although the mutation rate was low in ALMs, 36.4% were mutation positive at stage III/IV compared with 9.5% at stage I/II. This study confirmed associations among BRAF V600 mutations, pathological features and subtypes of melanoma. BRAF V600 mutations were more frequent in late-stage ALMs than in early-stage ALMs. Superficial spreading melanomas had similar mutation rates at all stages. These insights suggest improved treatment predictions for stage III/IV melanoma patients. PMID:25051202

  7. A new glucocerebrosidase-gene missense mutation responsible for neuronopathic Gaucher disease in Japanese patients.

    PubMed Central

    Kawame, H; Eto, Y

    1991-01-01

    We have identified a new T-to-A single-base substitution at nucleotide 3548 (in the genomic sequence) in exon 6 in the glucocerebrosidase gene from a patient with Gaucher disease type 3. This mutation caused a substitution of isoleucine for phenylalanine at amino acid residue 213 (of 497 residues in the mature protein). By in vitro expression study in cultured mammalian cells, this mutation resulted in deficient activity of glucocerebrosidase. By allele-specific oligonucleotide hybridization of selectively PCR-amplified DNA from eight unrelated Japanese Gaucher disease patients, this mutant allele was observed in other neuronopathic Japanese Gaucher disease patients, in moderately frequent occurrence (three of six neuronopathic patients). This observation suggests that this allele was one of severe [corrected] alleles which were related to the development of neurological manifestations of Gaucher disease. Images Figure 1 Figure 2 PMID:1840477

  8. Higher prevalence of Epstein-Barr virus DNA in deeper periodontal pockets of chronic periodontitis in Japanese patients.

    PubMed

    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

  9. Epiplakin Is a Paraneoplastic Pemphigus Autoantigen and Related to Bronchiolitis Obliterans in Japanese Patients.

    PubMed

    Tsuchisaka, Atsunari; Numata, Sanae; Teye, Kwesi; Natsuaki, Yohei; Kawakami, Tamihiro; Takeda, Yoshito; Wang, Wenqing; Ishikawa, Kazushi; Goto, Mizuki; Koga, Hiroshi; Sogame, Ryosuke; Ishii, Norito; Takamori, Shinzo; Hoshino, Tomoaki; Brandt, Oliver; Pas, Hendri H; Fujiwara, Sakuhei; Hashimoto, Takashi

    2016-02-01

    All plakin family proteins are known to be autoantigens in paraneoplastic pemphigus (PNP). In this study, we first examined whether PNP sera also react with epiplakin, another plakin protein, by various immunological methods using 48 Japanese PNP sera. Immunofluorescence confirmed that cultured keratinocytes expressed epiplakin. Epiplakin was detected by 72.9% of PNP sera by immunoprecipitation-immunoblotting with KU-8 cell extract, but not by immunoblotting of either normal human epidermal extract or KU-8 cell extract. Epiplakin was essentially not detected by 95 disease and normal control sera. Statistical analyses of various clinical and immunological findings revealed a significant correlation of the presence of anti-epiplakin antibodies with both bronchiolitis obliterans and mortality. No epiplakin-negative PNP case developed bronchiolitis obliterans. However, although 29.4% of European patients with PNP had bronchiolitis obliterans, significant correlation with anti-epiplakin autoantibodies was not observed. In further studies for lung, immunofluorescence showed the presence of epiplakin in normal human lung, particularly respiratory bronchiole, immunoprecipitation-immunoblotting showed that PNP sera reacted with epiplakin in cultured lung cells, and mice injected with polyclonal antibody specific to epiplakin histopathologically showed abnormal changes in small airway epithelia. These results indicated that epiplakin is one of the major PNP autoantigens and is related to PNP-related bronchiolitis obliterans. PMID:26802236

  10. Late-onset neuropsychological symptoms in a Japanese patient with megalencephalic leukoencephalopathy with subcortical cysts.

    PubMed

    Sugiura, C; Shiota, M; Maegaki, Y; Yoshida, K; Koeda, T; Kitahara, T; Ohno, K

    2006-10-01

    We herein report a Japanese patient with megalencephalic leukoencephalopathy with subcortical cysts (MLC) who developed late-onset neuropsychological symptoms. He demonstrated characteristic clinical features of MLC during childhood, such as slowly progressive megalencepaly, motor impairment with ataxia and spasticity, mild mental retardation, and well-controlled epilepsy. Thereafter, he showed specific neuropsychological symptoms, such as motor and vocal tics, compulsive behavior, perseveration, acquired stuttering, and dystonia since the age of 12. His performance abilities had been unchanged but his verbal abilities had degraded during the past 14 years. Higher cortical dysfunction tests revealed a frontal lobe dysfunction. On repeated brain MRI, a leukoencephalopathy with subcortical cysts remained stationary from infancy. On single photon emission computed tomography (SPECT), a hypoperfusion in the frontal lobe was detected at the age of 3.5 and 17, but the severity of hypoperfusion was also unchanged, respectively. Our results indicate that the frontal lobe dysfunction may be relevant to the late-onset neuropsychological symptoms with MLC. PMID:17236107

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

    PubMed

    Tamamaki, Kinko; Nishio, Hisahide

    2013-01-01

    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. PMID:23756658

  12. New susceptible variant of COQ2 gene in Japanese patients with sporadic multiple system atrophy

    PubMed Central

    Sun, Zhuoran; Ohta, Yasuyuki; Yamashita, Toru; Sato, Kota; Takemoto, Mami; Hishikawa, Nozomi

    2016-01-01

    Objective: The aim of this study was to analyze the association between the variations of coenzyme Q2 4-hydroxybenzoate polyprenyltransferase gene (COQ2) and Japanese patients with multiple system atrophy (MSA). Methods: We investigated the genetic variations in exons 1, 2, 6, and 7 of the COQ2 gene in 133 Japanese patients with MSA and 200 controls and analyzed the association between the variations and MSA. Results: Six DNA variations (G21S, L25V, V66L, P157S, V393A, and X422K) were found in the 133 patients with MSA, and G21S and X422K were new variations that had never been reported. V66L was a common variation that was found in all 133 patients with MSA. G21S, P157S, V393A, and X422K did not show gene frequency differences between patients with MSA and controls. On the other hand, L25V was newly proven to be the only risk factor of sporadic MSA with predominant olivopontocerebellar ataxia. Conclusions: The present study suggests L25V variant of COQ2 gene as a genetic risk factor in Japanese patients with MSA with cerebellar ataxia. PMID:27123473

  13. A comparison of clinical features among Japanese eating-disordered women with obsessive-compulsive disorder.

    PubMed

    Matsunaga, H; Miyata, A; Iwasaki, Y; Matsui, T; Fujimoto, K; Kiriike, N

    1999-01-01

    Clinical features, such as obsessive-compulsive disorder (OCD) symptoms, were investigated in Japanese women with DSM-III-R eating disorders (EDs) and concurrent OCD in comparison to age-matched women with OCD. Sixteen women with restricting anorexia nervosa (AN), 16 with bulimia nervosa (BN), and 16 with both AN and BN (BAN) showed commonality in a more elevated prevalence of OCD symptoms of symmetry and order compared with 18 OCD women. Among the personality disorders (PDs), likewise, obsessive-compulsive PD (OCPD) was more prevalent in each ED group compared with the OCD group. However, aggressive obsessions were more common in both BN and BAN subjects compared with AN subjects. Subjects with bulimic symptoms were also distinguished from AN subjects by impulsive features in behavior and personality. Thus, an elevated prevalence of aggressive obsessions along with an admixture of impulsive and compulsive features specifically characterized the clinical features of bulimic subjects with OCD. PMID:10509614

  14. 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

  15. Systematic molecular analyses of SHOX in Japanese patients with idiopathic short stature and Leri-Weill dyschondrosteosis.

    PubMed

    Shima, Hirohito; Tanaka, Toshiaki; Kamimaki, Tsutomu; Dateki, Sumito; Muroya, Koji; Horikawa, Reiko; Kanno, Junko; Adachi, Masanori; Naiki, Yasuhiro; Tanaka, Hiroyuki; Mabe, Hiroyo; Yagasaki, Hideaki; Kure, Shigeo; Matsubara, Yoichi; Tajima, Toshihiro; Kashimada, Kenichi; Ishii, Tomohiro; Asakura, Yumi; Fujiwara, Ikuma; Soneda, Shun; Nagasaki, Keisuke; Hamajima, Takashi; Kanzaki, Susumu; Jinno, Tomoko; Ogata, Tsutomu; Fukami, Maki

    2016-07-01

    The etiology of idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD) in European patients is known to include SHOX mutations and copy-number variations (CNVs) involving SHOX and/or the highly evolutionarily conserved non-coding DNA elements (CNEs) flanking the gene. However, the frequency and types of SHOX abnormalities in non-European patients and the clinical importance of mutations in the CNEs remains to be clarified. Here, we performed systematic molecular analyses of SHOX for 328 Japanese patients with ISS or LWD. SHOX abnormalities accounted for 3.8% of ISS and 50% of LWD cases. CNVs around SHOX were identified in 16 cases, although the ~47 kb deletion frequently reported in European patients was absent in our cases. Probably damaging mutations and benign/silent substitutions were detected in four cases, respectively. Although CNE-linked substitutions were detected in 15 cases, most of them affected poorly conserved nucleotides and were shared by unaffected individuals. These results suggest that the frequency and mutation spectrum of SHOX abnormalities are comparable between Asian and European patients, with the exception of a European-specific downstream deletion. Furthermore, this study highlights the clinical importance and genetic heterogeneity of the SHOX-flanking CNVs, and indicates a limited clinical significance of point mutations in the CNEs. PMID:26984564

  16. An experience in Japanese academic medicine.

    PubMed Central

    Tierney, L M

    1994-01-01

    The Japanese health care system has been highly praised for its universal access, freedom of patient choice, maintenance of a private system, and creative funding. Japanese citizens enjoy general good health, low infant mortality, and long life expectancy. Nevertheless, aspects of Japanese medical education, both graduate and undergraduate, and the structure of academic departments differ from those seen in the United States. A sabbatical spent teaching general internal medicine in Japan provided the experience for this review of the Japanese system. I describe the structure and function of departments of medicine and observations made at daily clinical teaching exercises in hospitals throughout the country. PMID:8160464

  17. 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 Central

    Foley, James E; Bhosekar, Vaishali; Kawamori, Ryuzo

    2016-01-01

    Background 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. Methods 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. Results 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, r2=0.36; and 0.41, r2=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). Conclusion 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

  18. Temperament and character of Japanese eating disorder patients.

    PubMed

    Nagata, Toshihiko; Oshima, Jun; Wada, Akira; Yamada, Hisashi; Iketani, Toshiya; Kiriike, Nobuo

    2003-01-01

    Previous studies consistently reported a link between bulimic behaviors and high Novelty Seeking (NS), as measured by the Temperament and Character Inventory (TCI). However, it remains unclear whether this relationship is universal and occurs in different environments. Subjects of the present study consisted of 66 patients with anorexia nervosa restricting type (AN-R), 59 patients with anorexia nervosa binge eating/ purging type (AN-BP), 101 patients with bulimia nervosa purging type (BN), and 75 controls. NS score in AN-R patients was significantly lower than that in controls, although NS in BN patients did not differ from that in controls. The temperament of AN-R patients seems to be universal, even in different environments. Conversely, something other than temperament might be important in the development of bulimia nervosa in Japan. PMID:12658623

  19. Systematic Validation of RNF213 Coding Variants in Japanese Patients With Moyamoya Disease

    PubMed Central

    Moteki, Yosuke; Onda, Hideaki; Kasuya, Hidetoshi; Yoneyama, Taku; Okada, Yoshikazu; Hirota, Kengo; Mukawa, Maki; Nariai, Tadashi; Mitani, Shohei; Akagawa, Hiroyuki

    2015-01-01

    Background 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. Methods and Results 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). Conclusions 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. PMID:25964206

  20. 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. PMID:24478188

  1. 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

  2. The effects of cochlear implantation in Japanese single-sided deafness patients: five case reports.

    PubMed

    Kitoh, Ryosuke; Moteki, Hideaki; Nishio, Shinya; Shinden, Seiichi; Kanzaki, Sho; Iwasaki, Satoshi; Ogawa, Kaoru; Usami, Shin-Ichi

    2016-05-01

    Conclusion Cochlear implantation (CI) for Japanese single-sided deafness patients resulted in improved speech perception, increased sound localization accuracy, and reduced tinnitus handicap. Objectives This study reports results for five adult SSD cases with CI, focusing on the benefits they obtained in terms of speech recognition, sound localization, and tinnitus handicap. Methods Five Japanese patients meeting the eligibility criteria were included in this study. All patients were implanted with a fully inserted MED-EL Concerto FLEX28® implant (MED-EL, Innsbruck, Austria). Speech perception outcomes in noise, as well as sound localization and tinnitus disturbance, were assessed pre-surgically and at 1, 3, 6, and 12 months after CI activation. Results The Japanese monosyllable test score in noise improved gradually after implantation. In some cases, speech perception ability appeared unstable, particularly in the first 1-6 months after implantation. The sound localization ability showed marked improvement in all cases, with the disturbance to daily life caused by tinnitus also decreasing in all cases from the early post-operative period. PMID:26882310

  3. 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

  4. Human obese gene: molecular screening in Japanese and Asian Indian NIDDM patients associated with obesity.

    PubMed

    Niki, T; Mori, H; Tamori, Y; Kishimoto-Hashirmoto, M; Ueno, H; Araki, S; Masugi, J; Sawant, N; Majithia, H R; Rais, N

    1996-05-01

    The mouse obese (ob) gene has recently been isolated through the positional cloning technique and has been proved to result in the obese and NIDDM phenotype in mice when mutated (Nature 372:425-432, 1994). More recently, it has been demonstrated, by experiments with recombinant ob protein, that ob gene product can cause mice, including ob/ob mice, diet-induced obesity mice, and normal mice, to lower their food intake and body weight (Science 269:540-549, 1995). To investigate the genetic and/or environmental influences underlying the development of NIDDM associated with obesity, we isolated and partially sequenced the human obese (OB) gene. The human OB gene isolated in this study encoded 167 amino acids and its open reading frame was revealed to be divided into two parts with an intermediate intron of approximately 2.4 kb. Using the single-strand conformation polymorphism (SSCP) technique, we screened Japanese and Asian Indian subjects for mutations in the protein coding regions of the OB gene. A total of 75 NIDDM patients with obesity (54 Japanese and 21 Asian Indians), 40 NIDDM patients without obesity (34 Japanese and 6 Asian Indians), and 34 Japanese patients with simple obesity showed no abnormal SSCP patterns in either component of the coding sequences. These results suggested that mutations in the coding regions of the OB gene are not likely to be commonly identifiable and that there would likely be a kind of obesity-associated NIDDM not caused by mutations of the OB gene. PMID:8621021

  5. 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. PMID:25701307

  6. Significantly Higher Cytokine and Chemokine Levels in Patients with Japanese Spotted Fever than in Those with Tsutsugamushi Disease

    PubMed Central

    Iwasaki, Hiromichi; Ikegaya, Satoshi; Takada, Nobuhiro; Tamaki, Yukiko; Tabara, Kenji; Ueda, Takanori

    2014-01-01

    Tetracyclines are administered to cure Japanese spotted fever (JSF) and tsutsugamushi disease (TD). It is generally said that the clinical course of JSF is worse than that of TD despite antibiotic treatment. The precise mechanism underlying the more severe clinical course of JSF is not fully understood. We therefore examined whether the differential cytokine profile between these two infectious diseases contributes to the difference in clinical severity. The serum concentrations of various cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and gamma interferon [IFN-γ]) and chemokines (IL-8, interferon-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], MIP-1β, and eotaxin) were measured in 32 TD and 21 JSF patients. The results showed that serum levels of TNF-α in the acute phases of TD and JSF were significantly increased, with a higher concentration of TNF-α in patients with JSF (mean, 39.9 pg/ml) than in those with TD (mean, 13.8 pg/ml). Comparatively higher levels of other cytokines and chemokines (IL-6, IFN-γ, IL-8, IP-10, MCP-1, MIP-1α, and MIP-1β) were also observed in the acute phase of JSF. The clinical severity score (3.67 ± 1.71) of JSF patients was higher than that of TD patients (1.47 ± 0.77). Our findings revealed that the cytokine and chemokine levels in the acute phase of JSF were significantly higher than those in the acute phase of TD. The differential cytokine levels may be related to the difference in clinical severity between JSF and TD. PMID:24671792

  7. 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

  8. 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

  9. Effects of sleepiness on survival in Japanese hemodialysis patients: J-DOPPS study.

    PubMed

    Iseki, Kunitoshi; Tsuruya, Kazuhiko; Kanda, Eiichiro; Nomura, Takanobu; Hirakata, Hideki

    2014-01-01

    Sleep disorder and poor sleep quality are common in chronic hemodialysis (HD) patients. They have been claimed as a cause of morbidity and mortality. The relationship between the degree of sleepiness and survival has not been studied. We studied the degree of sleepiness in 1,252 adult HD patients (age ≥20 years) recruited into the Dialysis Outcomes Practice Pattern Study in Japan (J-DOPPS III), using the Japanese version of the Epworth Sleepiness Scale (JESS) questionnaire. Demographic data were presented for three subgroups: low, intermediate, and high JESS score. Cox proportional hazard regression analysis was performed to estimate the independent effect of several variables on survival. The hazard ratio for mortality was 2.312 (95% CI 1.267-4.220; p = 0.006) for those with a high JESS score (vs. those with a low JESS score) after adjusting for age, vintage (length of time on HD), sex, diabetes, body mass index, cardiovascular disease, HD treatment regimen (time, frequency, and single-pool Kt/V), laboratory data (serum albumin, creatinine, and total cholesterol), and medication (antihypertensive drugs, erythropoietin, vitamin D, and phosphate binders). Patients ≥70 years of age with comorbid conditions (congestive heart failure, stroke, and diabetes) showed a significantly higher JESS score (≥16). The JESS score did not show interaction by age. Results showed that the degree of sleepiness is related to survival in Japanese HD patients, particularly in elderly patients. PMID:25572670

  10. 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. PMID:25757921

  11. Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients.

    PubMed

    Nitta, Hirohisa; Unoki, Motoko; Ichiyanagi, Kenji; Kosho, Tomoki; Shigemura, Tomonari; Takahashi, Hiroshi; Velasco, Guillaume; Francastel, Claire; Picard, Capucine; Kubota, Takeo; Sasaki, Hiroyuki

    2013-07-01

    Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder that shows DNA hypomethylation at pericentromeric satellite-2 and -3 repeats in chromosomes 1, 9 and 16. ICF syndrome is classified into two groups: type 1 (ICF1) patients have mutations in the DNMT3B gene and about half of type 2 (ICF2) patients have mutations in the ZBTB24 gene. Besides satellite-2 and -3 repeats, α-satellite repeats are also hypomethylated in ICF2. In this study, we report three novel ZBTB24 mutations in ICF2. A Japanese patient was homozygous for a missense mutation (C383Y), and a Cape Verdean patient was compound heterozygous for a nonsense mutation (K263X) and a frame-shift mutation (C327W fsX54). In addition, the second Japanese patient was homozygous for a previously reported nonsense mutation (R320X). The C383Y mutation abolished a C2H2 motif in one of the eight zinc-finger domains, and the other three mutations caused a complete or large loss of the zinc-finger domains. Our immunofluorescence analysis revealed that mouse Zbtb24 proteins possessing a mutation corresponding to either C383Y or R320X are mislocalized from pericentrometic heterochromatin, suggesting the importance of the zinc-finger domains in proper intranuclear localization of this protein. We further revealed that the proper localization of wild-type Zbtb24 protein does not require DNA methylation. PMID:23739126

  12. 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

  13. Cultural competence and health care: Japanese, Korean, and Indian patients in the United States.

    PubMed

    Andresen, J

    2001-01-01

    Cultural competence requires sensitivity to the diverse ethnic, religious, and cultural expectations of patients in our health care system. In the increasingly multicultural world of the city hospital, patients will benefit from increased cultural competency on the part of health care providers. This study interviews Japanese, Korean, and Indian immigrants to the United States, showing that these individuals hold vastly different expectations concerning: 1) when to seek medical assistance; 2) the role of the doctor in the community; 3) the role of the patient and the patient's family in conversations with the medical specialist; 4) the roles of doctors versus nurses; 5) issues of privacy and disclosure to patient and family; 6) organ donation; and 7) end-of-life care. The paper concludes with immigrants' views on what would make their medical experience in the United States more comfortable, and hence, potentially more beneficial to their mental and physical health. PMID:11908075

  14. Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls

    PubMed Central

    Ishikawa, Nobuhisa; Hattori, Noboru; Kohno, Nobuoki; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm

    2015-01-01

    Purpose To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups. Patients and methods This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures. Results The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001), neutrophils and MMP-9 (P<0.001), macrophages and KL-6 (P<0.01), total cell count and IL-8 (P<0.05), neutrophils and IL-8 (P<0.05), and macrophages and MMP-9 (P<0.05). Significant correlations were also observed between some inflammatory cells in sputum and biomarkers in serum, with the most significant between serum CC-16 and both total cell count (P<0.005) and neutrophils (P<0.005) in sputum. Conclusion These results provide evidence for the first time that COPD in Japanese patients is a multicomponent disease, involving both airway and systemic inflammation, in addition to airway obstruction. Therefore, intervention with anti-inflammatory therapy may provide additional

  15. A multicenter, open-label extension study of velaglucerase alfa in Japanese patients with Gaucher disease: Results after a cumulative treatment period of 24months.

    PubMed

    Ida, Hiroyuki; Tanaka, Akemi; Matsubayashi, Tomoko; Murayama, Kei; Hongo, Teruaki; Lee, Hak-Myung; Mellgard, Björn

    2016-07-01

    Enzyme replacement therapy (ERT) with exogenous glucocerebrosidase is indicated to treat symptomatic Gaucher disease (GD), a rare, inherited metabolic disorder. ERT with velaglucerase alfa, which is produced in a human cell line using gene activation technology, was studied in a 12-month phase III trial in Japanese patients with type 1 or 3 GD who were switched from imiglucerase ERT (n=6); the current, open-label, 12-month extension study was designed to assess longer-term safety and efficacy. Two adult and three pediatric patients (aged <18years) were enrolled into the extension study. Every-other-week intravenous infusions were administered for 63-78weeks at average doses between 51.5 and 60.7units/kg. Three non-serious adverse events were considered related to velaglucerase alfa treatment, but no patient discontinued from the study. Six serious but non-drug-related adverse events were reported. No patient tested positive for anti-velaglucerase alfa antibodies. Hemoglobin concentrations, platelet counts, and liver and spleen volumes (normalized to body weight) in these patients were generally stable over a cumulative 24-month period from the baseline of the parent trial. The data suggest that velaglucerase alfa was well tolerated and maintained clinical stability in Japanese GD patients over 2years after switching from imiglucerase. ClinicalTrials.gov identifier NCT01842841. PMID:27241455

  16. Clinical data mining related to the Japanese kampo concept "hie" (oversensitivity to coldness) in men and pre- and postmenopausal women.

    PubMed

    Tokunaga, H; Munakata, K; Katayama, K; Yamaguchi, R; Imoto, S; Miyano, S; Watanabe, K

    2014-01-01

    "Hie" is a subjective oversensitivity to cold and a condition experienced in 60% of Japanese citizens. The condition of hie has not been documented in Western medicine. However, in Kampo medicine, hie is an important target of treatment, because it has been considered one of the sources of all kinds of diseases. This study aimed to clarify the symptoms and findings associated with hie and contribute to increased precision in hie diagnosis. During 2005-2006, data from interviews of 1691 patients during their initial visit to the Kampo Clinic of Keio University Hospital were analyzed using a classification and regression tree (CART) analysis, a data mining technique. Symptoms and findings characteristic of each group are follows as, postmenopausal women: fatigability, absence of lower abdominal pain, and absence of hot flashes of feet: women with menstruation: leg swelling, knee pain, and abdominal pain; men: insomnia, leg weakness, and absence of excess saliva. From the perspective of Kampo medicine the result suggested that the feature of hie condition in postmenopausal women, women with menstruation, and men is statistically different. PMID:24707313

  17. 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.

  18. The clinical features and prognosis of rhabdomyosarcoma: follow-up studies on pediatric tumors from the Japanese Pediatric Tumor Registry 1971-1980. Part II. Committee of Malignant Tumors, Japanese Society of Pediatric Surgeons.

    PubMed

    Nakada, K

    1990-09-01

    A retrospective study was conducted on 126 patients with rhabdomyosarcoma enrolled in the Japanese Pediatric Tumor Registry between 1971 and 1980. The age of the patients ranged from less than 1 year to 15 years, and the male to female ratio was 1.3:1.0. Primary sites included the pelvis (37.3 per cent), abdomen (23.8 per cent), head and neck (21.4 per cent), thorax (9.5 per cent), extremities (6.4 per cent) and unknown (1.6 per cent). According to the staging system of the Japanese Society of Pediatric Surgeons, the extent of disease was classified into stages Ia (26.2 per cent of the total); Ib (14.6 per cent); II (12.6 per cent), III (29.1 per cent) and IV (17.5 per cent). The clinical stage was significantly correlated with survival outcome in this series (p less than 0.05). Age, sex, histology and primary site per se had no independent prognostic influence on tumor-free survival. With regard to treatment modalities, surgery was performed in 94.0 per cent of the patients, and radiotherapy at a mean dose of 37 Gy, and/or multi-agent chemotherapy in 41.7 per cent and 80.0 per cent, respectively. The patients who underwent total excision had a better survival outcome than those who did not (p less than 0.05). Combination chemotherapy such as VAC was more commonly administered in the latter study period. The overall 2-year tumor-free survival rate (2YTFSR) significantly improved from 24.0 per cent in the former period between 1971 and 1975 to 48.7 per cent in the latter period between 1976 and 1980 (p less than 0.05). PMID:2243442

  19. Upregulation of interleukin-33 in the epidermis of two Japanese patients with Netherton syndrome.

    PubMed

    Konishi, Tomoko; Tsuda, Tatsuya; Sakaguchi, Yoshiko; Imai, Yasutomo; Ito, Takashi; Hirota, Seiichi; Yamanishi, Kiyofumi

    2014-03-01

    Netherton syndrome (NS) is a rare autosomal recessive disorder which is caused by mutations in the SPINK5 gene encoding the serine-protease inhibitor LEKTI. Characteristic symptoms of NS include erythroderma with diffuse desquamation, hair abnormalities and atopic manifestations. Here, we report two Japanese patients with NS, one of whom had a novel mutation in the SPINK5 gene which leads to p.C367Lfs*3. The upregulation of interleukin-33 (IL-33) was evident in basal and thickened lower spinous layers of the epidermis in those cases. This suggests that IL-33 may be involved in the pathophysiology of NS as well as in atopic dermatitis. PMID:24506793

  20. Association of Diabetes and Hemodialysis With Ankle Pressure and Ankle-Brachial Index in Japanese Patients With Critical Limb Ischemia

    PubMed Central

    Takahara, Mitsuyoshi; Kaneto, Hideaki; Iida, Osamu; Katakami, Naoto; Matsuoka, Taka-aki; Ikeda, Masahiko; Shimomura, Iichiro

    2012-01-01

    OBJECTIVE To investigate whether diabetes and regular hemodialysis are associated with false elevation of ankle systolic blood pressure and ankle-brachial systolic pressure index (ABI) because of their arterial calcification in patients with critical limb ischemia (CLI). RESEARCH DESIGN AND METHODS We recruited 269 Japanese patients who underwent endovascular therapy for CLI. Ankle systolic blood pressure and ABI were assessed before endovascular therapy. Arterial stenosis and calcification were evaluated angiographically. We investigated the associations among clinical comorbidities, arterial calcification, and measurements of ankle systolic blood pressure and ABI. RESULTS Ankle systolic blood pressure was 85 ± 56 mmHg, and ABI was 0.59 ± 0.37. Arterial calcification was observed in 69% of the patients. The prevalence of diabetes and regular hemodialysis was 71 and 47%. Diabetes and regular hemodialysis were both significantly associated with the presence of arterial calcification; their adjusted odds ratios were 2.33 (P = 0.01) and 7.40 (P < 0.01), respectively. However, there was no significant difference in ankle systolic blood pressure or ABI level between those with and without these comorbidities. Furthermore, the presence of arterial calcification was not associated with ankle systolic blood pressure or ABI level, whereas arterial stenoses of all segments in the lower body had independent associations with reduced ankle systolic blood pressure and ABI level. CONCLUSIONS Diabetes and regular hemodialysis were significantly associated with arterial calcification, but not with elevated measurements of ankle systolic blood pressure or ABI, in CLI patients. PMID:22723344

  1. Gonadal function, fertility, and reproductive medicine in childhood and adolescent cancer patients: a national survey of Japanese pediatric endocrinologists.

    PubMed

    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

    2016-04-01

    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

  2. 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. PMID:24493180

  3. 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. PMID:11442883

  4. 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

  5. Phase I study of olaratumab in Japanese patients with advanced solid tumors.

    PubMed

    Doi, Toshihiko; Ma, Yan; Dontabhaktuni, Aruna; Nippgen, Cornelia; Nippgen, Johannes; Ohtsu, Atsushi

    2014-07-01

    Olaratumab (IMC-3G3) is a fully human IgG1 monoclonal antibody that selectively binds the external domain of human platelet-derived growth factor receptor-α with high affinity and blocks ligand binding. This was a single-center, dose-escalation, phase I trial of olaratumab in Japanese patients with advanced/refractory solid malignancies. Three to six patients were enrolled into each of three cohorts: Patients received i.v. olaratumab: 10 mg/kg on days 1 and 8 every 3 weeks (cohort 1); 20 mg/kg every 2 weeks (cohort 2); and 15 mg/kg on days 1 and 8 every 3 weeks (cohort 3). Doses were escalated from cohort 1 through cohort 3. The primary objective was to establish the safety and pharmacokinetic profile of olaratumab. Sixteen patients were treated across three cohorts. There were no dose-limiting toxicities, so the maximum tolerated dose was not reached. The most common olaratumab-related treatment-emergent adverse events (TEAEs) were proteinuria (25.0%) and elevated aspartate transaminase (12.5%). One patient (cohort 2) had two olaratumab-related Grade 3 TEAEs (increased aspartate aminotransferase and tumor hemorrhage); otherwise, olaratumab-related TEAEs were Grade 1/2. Seven patients (43.8%) had a best response of stable disease. Based on the pharmacokinetic concentration profile of olaratumab, the trough concentrations following single and multiple doses at 15 mg/kg on days 1 and 8 every 3 weeks (cohort 3) and multiple doses at 20 mg/kg every 2 weeks (cohort 2) were above the 155 μg/mL target. Thus, these two doses could represent an acceptable schedule for future trials in Japanese patients. Olaratumab had an acceptable safety profile and was well tolerated. PMID:24816152

  6. 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

  7. The Japanese version of Skindex-16: a brief quality-of-life measure for patients with skin diseases.

    PubMed

    Higaki, Yuko; Kawamoto, Kyoko; Kamo, Toshiko; Horikawa, Naoshi; Kawashima, Makoto; Chren, Mary-Margaret

    2002-11-01

    A practical quality-of-life measure applicable to patients with skin diseases is necessary. Recently developed dermatological quality-of-life measures must be translated and adapted for use in cultures other than the ones in which they were created. In this study, we translated and adapted culturally into Japanese a skin-disease-specific, brief quality-of-life measure, Skindex-16, and studied its reliability and validity. Forward-and back-translations of Skindex-16 were carried out. Six doubtful items as well as the term "skin condition" required a second forward- and back-translation to reach satisfactory agreement with the original instrument. Cross-cultural adaptation and cross-sectional questionnaire studies were then performed to evaluate the reliability and validity of the instrument. One hundred patients and 30 healthy adults responded to the Japanese version. The internal-consistency reliability of the final Japanese version of Skindex-16 was high (range of Cronbach's alpha for each scale, symptoms, emotions, and functioning, was 0.83-0.92). The Japanese version showed construct and content validity. As hypothesized, scores for dermatological patients were higher than those for healthy persons (mean global scores 36 +/- 23 vs 1 +/- 2, p < 0.001) and scores for patients with inflammatory diseases were higher than those for patients with isolated skin lesions (mean global scores 48 +/- 21 vs 22 +/- 17, p < 0.001), indicating a poorer quality of life. Most patients' responses to an open-ended question about their skin disease were similar to those of the American responders and were addressed according to the items. In conclusion, we have developed a semantically equivalent translation of Skindex-16 into Japanese. It is a reliable and valid measure of the effects of skin disease on the quality of life in Japanese patients. PMID:12484430

  8. 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

  9. 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

  10. Analysis of SLITRK1 in Japanese patients with Tourette syndrome using a next-generation sequencer.

    PubMed

    Inai, Aya; Tochigi, Mamoru; Kuwabara, Hitoshi; Nishimura, Fumichika; Kato, Kayoko; Eriguchi, Yosuke; Shimada, Takafumi; Furukawa, Masaomi; Kawamura, Yoshiya; Sasaki, Tsukasa; Kakiuchi, Chihiro; Kasai, Kiyoto; Kano, Yukiko

    2015-12-01

    The SLITRK1 (Slit and Trk-like 1) gene has been suggested to be a promising candidate for Tourette syndrome (TS) since the first report that identified its two rare variants adjacent to the chromosome inversion in a TS child with inv(13) (q31.1;q33.1). A series of replication studies have been carried out, whereas the role of the gene has not been elucidated. The present study aimed to determine whether the two or novel nonsynonymous variants were identified in Japanese TS patients and carry out an association analysis of the gene in a Japanese population. We did not observe the two or any novel nonsynonymous variants in the gene. In contrast, a significant difference was observed in the distributions of the haplotypes consisting of rs9546538, rs9531520, and rs9593835 between the patients and the controls. This result may partially support the implication of SLITRK1 in the pathogenesis of TS, warranting further studies of the gene. PMID:26317387

  11. 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. PMID:27169398

  12. [Invasive Campylobacter jejuni/coli Infections: 9 Case Reports at a Single Center between 2000 and 2015, and a Review of Literature Describing Japanese Patients].

    PubMed

    Tasaka, Keiji; Matsubara, Kousaku; Nigami, Hiroyuki; Iwata, Aya; Isome, Kenichi; Yamamoto, Go

    2016-05-01

    There have been few coherent reports on extraintestinal infection or bacteremia caused by Campylobacter jejuni (C. jejuni) or C. coli in Japan. To clarify the clinical and microbiological characteristics of invasive infections caused by these two species, we retrospectively analyzed the records of patients from whom these pathogens had been isolated from sterile sites between 2000 and 2015. During this study period, we identified 9 patients. The clinical syndrome of all of these patients was bacteremia. Three patients had underlying diseases with both liver cirrhosis and malignant neoplasm, and all of these patients were aged 60 years or older. The remaining 6 patients were immunocompetent and younger than 40 years of age. All 9 patients had a fever of 38.5 degrees C or higher. The proportion of patients with gastrointestinal symptoms was lower for the 3 patients with underlying diseases, compared with the 6 patients without underlying diseases (1/3 cases vs, 4/6 cases). Of the 8 strains evaluated for antimicrobial susceptibility, all were susceptible to imipenem/cilastatin, kanamycin and erythromycin, and 2 were resistant to levofloxacin. Antimicrobial treatment was administered to 8 patients, but one spontaneously recovered without any treatment. We were able to follow the outcomes of 8 patients, and all of these patients completely recovered without relapses. We also reviewed 14 Japanese patients reported in the Japanese and English literature and found similar clinical features consisting of a high-grade fever and an association with underlying diseases and gastrointestinal symptoms. Of note, 3 agammaglobulinemic patients presented with bacteremia and extraintestinal infections and had multiple relapses. Based on the findings of our 9 cases and previous reports, the affected patients were divided into two groups according to clinical syndrome and therapeutic intervention. One group consisted of previously healthy children or young adults showing bacteremia

  13. 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

  14. Prevalence and clinical characterization of Japanese diabetes mellitus with an A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA{sup Leu (UUR)} gene

    SciTech Connect

    Odawara, Masato; Sasaki, Kayoko; Yamashita, Kamejiro

    1995-04-01

    An A-to-G mutation at nucleotide position 3243 of the mitochondrial genome has been associated with insulin-dependent diabetes mellitus (IDDM) and with noninsulin-dependent diabetes mellitus (NIDDM) with deafness. We investigated the prevalence of this mutation in Japanese patients with IDDM, NIDDM, and impaired glucose tolerance (IGT) and in nondiabetic control individuals, and we identified it in 3 of 300 patients with NIDDM or IGT (1.0%). None of these individuals had significant sensorineural hearing loss. None of the 94 IDDM or the 115 nondiabetic control subjects was positive for this mutation. Oral glucose tolerance test revealed that a 57-yr-old male with this mutation was rather hyperinsulinemic in the fasting state. The insulin secretion in this patient decreased with age; he did not complain of any hearing disorder, although audiometry revealed a slight elevation of hearing threshold at high frequencies. In conclusion, we found that a mitochondrial gene mutation at nucleotide position 3243 was present in about 1% of NIDDM patients including those patients with IGT. The subtype of diabetes mellitus with this mutation may have a clinical profile similar to that found in patients with NIDDM commonly seen in outpatient clinics. 25 refs., 2 figs., 1 tab.

  15. Social Orientation and Diabetes-Related Distress in Japanese and American Patients with Type 2 Diabetes

    PubMed Central

    Ikeda, Kaori; Fujimoto, Shimpei; Morling, Beth; Ayano-Takahara, Shiho; Carroll, Andrew E.; Harashima, Shin-ichi; Uchida, Yukiko; Inagaki, Nobuya

    2014-01-01

    Objective 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. Research Design and Methods 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. Results 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. Conclusions 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. PMID:25333692

  16. Novel mutations in the COL2A1 gene in Japanese patients with Stickler syndrome.

    PubMed

    Kondo, Hiroyuki; Matsushita, Itsuka; Nagata, Tatsuo; Hayashi, Takaaki; Kakinoki, Masashi; Uchio, Eiichi; Kondo, Mineo; Ohji, Masahito; Kusaka, Shunji

    2016-01-01

    Stickler syndrome is an inherited connective tissue disorder that affects the eyes, cartilage and articular tissues. The phenotypes of Stickler syndrome include congenital high myopia, retinal detachment, premature joint degeneration, hearing impairment and craniofacial anomalies, such as cleft palate and midline facial hypoplasia. The disease is genetically heterogeneous, and the majority of the cases are caused by mutations in the COL2A1 gene. We examined 40 Japanese patients with Stickler syndrome from 23 families to determine whether they had mutations in the COL2A1 gene. This analysis was conducted by examining each patient's genomic DNA by Sanger sequencing. Five nonsense, 4 splicing and 8 deletion mutations in the COL2A1 gene were identified, accounting for 21 of the 23 families. Different mutations of the COL2A1 gene were associated with similar phenotypes but with different degrees of expressivity. PMID:27408751

  17. Genetic mutation analysis in Japanese patients with non-syndromic congenital heart disease.

    PubMed

    Yoshida, Akiko; Morisaki, Hiroko; Nakaji, Mai; Kitano, Masataka; Kim, Ki-Sung; Sagawa, Koichi; Ishikawa, Shiro; Satokata, Ichiro; Mitani, Yoshihide; Kato, Hitoshi; Hamaoka, Kenji; Echigo, Shigeyuki; Shiraishi, Isao; Morisaki, Takayuki

    2016-02-01

    Congenital heart disease (CHD) is the most common birth defect occurring in humans and some transcriptional factors have been identified as causative. However, additional mutation analysis of these genes is necessary to develop effective diagnostic and medical treatment methods. We conducted sequence analysis of the coding regions of NKX2.5, GATA4, TBX1, TBX5, TBX20, CFC1 and ZIC3 in 111 Japanese patients with non-syndromic CHD and 9 of their relatives. All patient samples were also analyzed by multiplex ligation-dependent probe amplification using probes involved in chromosome deletion related to CHD. Five novel variations of TBX5, GATA4 and TBX20 were detected in 6 of the patients, whereas none were found in 200 controls. The TBX5 variation p.Pro108Thr, located in the T-box domain, was identified in a patient with tricuspid atresia, an exon-intron boundary variation of GATA4 (IVS4+5G>A) was detected in a Tetralogy of Fallot patient and an 8p23 microdeletion was detected in one patient with atrioventricular septal defect and psychomotor delay. A total of seven non-synonymous polymorphisms were found in the patients and controls. Accumulation of novel variations of genes involving the cardiac development may be required for better understanding of CHD. PMID:26490186

  18. Development of a prediction system for anti-tuberculosis drug-induced liver injury in Japanese patients

    PubMed Central

    Mushiroda, Taisei; Yanai, Hideki; Yoshiyama, Takashi; Sasaki, Yuka; Okumura, Masao; Ogata, Hideo; Tokunaga, Katsushi

    2016-01-01

    Drug-induced liver injury (DILI) is a common adverse drug reaction in patients receiving antituberculosis (anti-TB) treatment. Among the anti-TB agents, isoniazid (INH) is the primary drug that causes hepatotoxicity in TB patients with DILI. Previous reports in several populations have consistently demonstrated an association between polymorphisms in the N-acetyltransferase 2 (NAT2) gene, which is responsible for INH hepatic metabolism, and a risk of DILI in TB patients. In this study, the genetic and baseline clinical data from 366 Japanese patients with TB (73 patients with DILI and 293 without DILI) were used to develop a system to predict DILI risk due to anti-TB agents. The distribution of the NAT2 acetylator status among the TB patients with DILI was 31 (42.5%), 29 (39.7%), and 13 (17.8%) for rapid, intermediate, and slow acetylators, respectively. A significant association was observed between NAT2 slow acetylators and DILI risk (odds ratio 4.32, 95% confidence interval 1.93–9.66, P value=5.56×10−4). A logistic regression model based on age and NAT2 genotype revealed that the area under the curve for the receiver-operating characteristic curve was 0.717. The findings demonstrated that slow NAT2 acetylator status is a significant predictor of the risk of DILI by anti-TB agents, and a personalized anti-TB treatment approach may aid in making treatment decisions and reducing the incidence of DILI. PMID:27340556

  19. Development of a prediction system for anti-tuberculosis drug-induced liver injury in Japanese patients.

    PubMed

    Mushiroda, Taisei; Yanai, Hideki; Yoshiyama, Takashi; Sasaki, Yuka; Okumura, Masao; Ogata, Hideo; Tokunaga, Katsushi

    2016-01-01

    Drug-induced liver injury (DILI) is a common adverse drug reaction in patients receiving antituberculosis (anti-TB) treatment. Among the anti-TB agents, isoniazid (INH) is the primary drug that causes hepatotoxicity in TB patients with DILI. Previous reports in several populations have consistently demonstrated an association between polymorphisms in the N-acetyltransferase 2 (NAT2) gene, which is responsible for INH hepatic metabolism, and a risk of DILI in TB patients. In this study, the genetic and baseline clinical data from 366 Japanese patients with TB (73 patients with DILI and 293 without DILI) were used to develop a system to predict DILI risk due to anti-TB agents. The distribution of the NAT2 acetylator status among the TB patients with DILI was 31 (42.5%), 29 (39.7%), and 13 (17.8%) for rapid, intermediate, and slow acetylators, respectively. A significant association was observed between NAT2 slow acetylators and DILI risk (odds ratio 4.32, 95% confidence interval 1.93-9.66, P value=5.56×10(-4)). A logistic regression model based on age and NAT2 genotype revealed that the area under the curve for the receiver-operating characteristic curve was 0.717. The findings demonstrated that slow NAT2 acetylator status is a significant predictor of the risk of DILI by anti-TB agents, and a personalized anti-TB treatment approach may aid in making treatment decisions and reducing the incidence of DILI. PMID:27340556

  20. Comparation of clinical and paraclinical findings among patient with Kawasaki disease in Bandar abbas Koodakan Hospital in 2011-14

    NASA Astrophysics Data System (ADS)

    Borjali, Davood

    Title: Comparation of clinical and paraclinical findings among patient with Kawasaki disease in Bandar abbas Koodakan Hospital in 2011-14 Kawasaki disease(KD) is a kind of vasculitis diagnosed by clinical manifestation and it caused acquired heart disease in children because of coronary arteries involvement. Method: patient divided to three group of American Japanese and incomplete and also study in two group according to fever days and then clinical features and laboratory data were checked. Result: A total of 150 patients were enrolled during the study period. number of patients with incomplete Kawasaki disease was 128 american group was 28 and Japanese was 4 patients, the most prevalent symptom was scaling of extremities(61 bladder most seen in group with fever more than five days. Keyword: Kawasaki , epidemiology , criteria

  1. Japanese encephalitis (JE). Part I: clinical profile of 1,282 adult acute cases of four epidemics.

    PubMed

    Sarkari, N B S; Thacker, A K; Barthwal, S P; Mishra, V K; Prapann, Shiv; Srivastava, Deepak; Sarkari, M

    2012-01-01

    Japanese encephalitis (JE) is numerically the most important global cause of encephalitis and so far confirmed to have caused major epidemics in India. Most of the reported studies have been in children. This largest study involving only adults, belonging to four epidemics, is being reported from Gorakhpur. The aim of this study is to detail the acute clinical profile (not viral) outcome and to classify the sequelae at discharge. This prospective study involved 1,282 adult patients initially diagnosed as JE admitted during the epidemics of 1978, 1980, 1988, and 1989, on identical clinical presentation and CSF examination. In the meantime, the diagnosis of JE was confirmed by serological and/or virological studies in only a representative number of samples (649 of 1,282 cases). Eighty-three left against medical advice (LAMA) at various stages, so 1,199 of 1,282 were available for the study. Peak incidence of [1,061 of 1,282 (83%)] of clinically suspected cases was from September 15 to November 2. Serum IgM and IgG were positive in high titers in 50.87% (330 of 649) and IgM positive in CSF in 88.75% (109 of 123) of the cases. JE virus could be isolated from CSF and brain tissue in 5 of 5 and 4 of 5 samples, respectively. Altered sensorium (AS) in (96%), convulsions (86%), and headache (85%) were the main symptoms for hospitalization by the third day of the onset. Other neurological features included hyperkinetic movements in 593 of 1,282 (46%)-choreoathetoid in 490 (83%) and bizarre, ill-defined in 103 (17%). The features of brain stem involvement consisted of opsoclonus (20%), gaze palsies (16%), and pupillary changes (48%) with waxing and waning character. Cerebellar signs were distinctly absent. Dystonia and decerebrate rigidity was observed in 43 and 6%, respectively, paralytic features in 17% and seizures in 30%. Many non-neurological features of prognostic importance included abnormal breathing patterns (ABP) (45%), pulmonary edema (PO) (33%), and upper

  2. Patient safety education at Japanese medical schools: results of a nationwide survey

    PubMed Central

    2012-01-01

    Background Patient safety education, including error prevention strategies and management of adverse events, has become a topic of worldwide concern. The importance of the patient safety is also recognized in Japan following two serious medical accidents in 1999. Furthermore, educational curriculum guideline revisions in 2008 by relevant the Ministry of Education includes patient safety as part of the core medical curriculum. However, little is known about the patient safety education in Japanese medical schools partly because a comprehensive study has not yet been conducted in this field. Therefore, we have conducted a nationwide survey in order to clarify the current status of patient safety education at medical schools in Japan. Results Response rate was 60.0% (n = 48/80). Ninety-eight-percent of respondents (n = 47/48) reported integration of patient safety education into their curricula. Thirty-nine percent reported devoting less than five hours to the topic. All schools that teach patient safety reported use of lecture based teaching methods while few used alternative methods, such as role-playing or in-hospital training. Topics related to medical error theory and legal ramifications of error are widely taught while practical topics related to error analysis such as root cause analysis are less often covered. Conclusions Based on responses to our survey, most Japanese medical schools have incorporated the topic of patient safety into their curricula. However, the number of hours devoted to the patient safety education is far from the sufficient level with forty percent of medical schools that devote five hours or less to it. In addition, most medical schools employ only the lecture based learning, lacking diversity in teaching methods. Although most medical schools cover basic error theory, error analysis is taught at fewer schools. We still need to make improvements to our medical safety curricula. We believe that this study has the implications for

  3. Influence of painful physical symptoms in the treatment of Japanese patients with melancholic major depressive disorder: A prospective cohort study.

    PubMed

    Sekine, Atsushi; Hozumi, Satoshi; Shimizu, Tetsuo

    2016-08-30

    The aim of this study was to clarify how painful physical symptoms affect treatment outcomes in patients with melancholic major depressive disorder. The subjects comprised 100 consecutive Japanese outpatients with melancholic major depressive disorder who visited our clinic from October 2011 to October 2014. All subjects were interviewed for Diagnostic and Statistical Manual of Mental Disorders Axis 2, 3, and 4 and family history of major depressive disorder, and then grouped according to the presence of painful physical symptoms. We evaluated painful physical symptoms at baseline and after 12, 24, and 36 weeks of treatment and scores on the 17-item Hamilton Rating Scale for Depression, compared major depressive disorder remission between groups, and assessed responsiveness to antidepressants. The group with painful physical symptoms had a significantly more positive family history of major depressive disorder. The major depressive disorder remission rate was high in both groups, and no significant differences were observed. However, a significant relationship between major depressive disorder and painful physical symptoms remission was observed in the group with painful physical symptoms. A significantly higher number of remitted patients with painful physical symptoms (N=61) were administered serotonin-noradrenaline reuptake inhibitors, with significantly more receiving duloxetine than milnacipran. PMID:27294798

  4. Subgroup analysis of phase 3 studies of dulaglutide in Japanese patients with type 2 diabetes.

    PubMed

    Onishi, Yukiko; Oura, Tomonori; Nishiyama, Hiroshi; Ohyama, Sumika; Takeuchi, Masakazu; Iwamoto, Noriyuki

    2016-03-31

    The efficacy and tolerability of once weekly dulaglutide 0.75 mg in Japanese patients with type 2 diabetes (T2D) were evaluated by subgroups defined by key demographic characteristics. This post hoc analysis included data from patients who received dulaglutide 0.75 mg for up to 26 weeks in three phase 3 trials (one open-label, randomized; one double-blind and open-label, randomized; one open-label, nonrandomized). Patients were classified into subgroups on the basis of sex (male, female), age (<65, ≥65 years), body weight (<70, ≥70 kg), body mass index (BMI; <25, ≥25 kg/m(2)), duration of diabetes (<7, ≥7 years), HbA1c (≤8.5, >8.5%), use of concomitant sulfonylurea (yes, no), and use of concomitant biguanide (yes, no). Efficacy measures analyzed were changes from baseline in HbA1c and body weight and percentages of patients achieving HbA1c <7.0%. Safety measures analyzed were incidence of hypoglycemia and nausea and change from baseline in seated pulse rate. A total of 855 patients were analyzed. Once weekly dulaglutide 0.75 mg improved blood glucose control as measured by HbA1c regardless of patient characteristics; patients with higher baseline HbA1c values had greater improvements compared to patients with lower baseline values. Weight loss was greater in patients with lower baseline HbA1c and in patients taking concomitant biguanides. Concomitant use of sulfonylureas had the greatest effect on the incidence of hypoglycemia. Treatment of T2D with once weekly dulaglutide 0.75 mg for 26 weeks was associated with significant improvement in glycemic control irrespective of age, sex, duration of diabetes, body weight, BMI, or concomitant medication. PMID:26698689

  5. Phase I trial of volasertib, a Polo-like kinase inhibitor, in Japanese patients with acute myeloid leukemia.

    PubMed

    Kobayashi, Yukio; Yamauchi, Takahiro; Kiyoi, Hitoshi; Sakura, Toru; Hata, Tomoko; Ando, Kiyoshi; Watabe, Aiko; Harada, Akiko; Taube, Tillmann; Miyazaki, Yasushi; Naoe, Tomoki

    2015-11-01

    This phase I trial conducted in Japanese patients with acute myeloid leukemia evaluated the safety, maximum tolerated dose and pharmacokinetics of volasertib (BI 6727), a selective Polo-like kinase inhibitor. The primary endpoints were the maximum tolerated dose of volasertib and the incidence of dose-limiting toxicities. Secondary endpoints were best response and remission duration. Other endpoints included safety and pharmacokinetics. Patients who were ineligible for standard induction therapy or with relapsed or refractory disease received volasertib monotherapy as a 2-h infusion on days 1 and 15 of a 28-day cycle, with dose escalation following a 3 + 3 design. A total of 19 patients were treated with three volasertib doses: 350, 400 and 450 mg. One patient receiving volasertib 450 mg reported a dose-limiting toxicity of grade 4 abnormal liver function test and 450 mg was determined as the maximum tolerated dose. The most frequently reported adverse events were febrile neutropenia (78.9%), decreased appetite (42.1%), nausea and rash (36.8% each), and sepsis, fatigue, hypokalemia, stomatitis and epistaxis (26.3% each). Best responses were complete remission (n = 3), complete remission with incomplete blood count recovery (n = 3) and partial remission (n = 1). The median remission duration of the six patients with complete remission or complete remission with incomplete blood count recovery was 85 days (range 56-358). Volasertib exhibited multi-compartmental pharmacokinetic behavior with a fast distribution after the end of infusion followed by slower elimination phases. Volasertib monotherapy was clinically manageable with acceptable adverse events and anti-leukemic activity. PMID:26471242

  6. Long-term incidence and prognostic factors of the progression of new coronary lesions in Japanese coronary artery disease patients after percutaneous coronary intervention.

    PubMed

    Kaneko, Hidehiro; Yajima, Junji; Oikawa, Yuji; Tanaka, Shingo; Fukamachi, Daisuke; Suzuki, Shinya; Sagara, Koichi; Otsuka, Takayuki; Matsuno, Shunsuke; Kano, Hiroto; Uejima, Tokuhisa; Koike, Akira; Nagashima, Kazuyuki; Kirigaya, Hajime; Sawada, Hitoshi; Aizawa, Tadanori; Yamashita, Takeshi

    2014-07-01

    Revascularization of an initially non-target site due to its progression as a new culprit lesion has emerged as a new therapeutic target of coronary artery disease (CAD) in the era of drug-eluting stents. Using the Shinken database, a single-hospital-based cohort, we aimed to clarify the incidence and prognostic factors for progression of previously non-significant coronary portions after prior percutaneous coronary intervention (PCI) in Japanese CAD patients. We selected from the Shinken database a single-hospital-based cohort of Japanese patients (n = 15227) who visited the Cardiovascular Institute between 2004 and 2010 to undergo PCI. This study included 1,214 patients (median follow-up period, 1,032 ± 704 days). Additional clinically driven PCI to treat previously non-significant lesions was performed in 152 patients. The cumulative rate of new-lesion PCI was 9.5 % at 1 year, 14.4 % at 3 years, and 17.6 % at 5 years. There was no difference in background clinical characteristics between patients with and without additional PCI. Prevalence of multi-vessel disease (MVD) (82 vs. 57 %, p < 0.001) and obesity (47 vs. 38 %, p = 0.028) were significantly higher and high-density lipoprotein cholesterol (HDL) level (51 ± 15 vs. 47 ± 12 mg/dl, p < 0.001) was significantly lower in patients with additional PCI than those without. Patients using insulin (6 vs. 3 %, p = 0.035) were more common in patients with additional PCI. Multivariate analysis showed that MVD, lower HDL, and insulin use were independent determinants of progression of new culprit coronary lesions. In conclusion, progression of new coronary lesions was common and new-lesion PCI continued to occur beyond 1 year after PCI without attenuation of their annual incidences up to 5 years. Greater coronary artery disease burden, low HDL, and insulin-dependent DM were independent predictors of progression of new culprit coronary lesions. PMID:23807613

  7. Analysis of Patient Service Time in Ambulatory Clinics: Patient Tracking

    PubMed Central

    Zerbe, Tony R.; Zerbe, Shirleen D.

    1990-01-01

    Historically, analysis of patient service time (patient tracking) in ambulatory clinics has been performed manually. A case study of Eye and Ear Clinic in Pittsburgh, PA, revealed that this approach to patient data collection was prone to clerical error and did not satisfy the clinic's information-processing needs. Initial attempts at automation identified the features required of a successful computerized scheduling and patient tracking system. These essential features are being designed into a prototype system using a local area network platform. The software for this system employs bar code technology to log patients' movement. The resultant data permits analysis of clinic operation and rapid response to unforseen events. Patient information is presented in a color-coded format to permit-at-a-glance comprehension of data on multiple patients (up to 76) simultaneously. A scheduling module projects patients' arrival time and ensures availability of critical resources.

  8. Amebiasis in HIV-1-infected Japanese men: clinical features and response to therapy.

    PubMed

    Watanabe, Koji; Gatanaga, Hiroyuki; Escueta-de Cadiz, Aleyla; Tanuma, Junko; Nozaki, Tomoyoshi; Oka, Shinichi

    2011-09-01

    Invasive amebic diseases caused by Entamoeba histolytica are increasing among men who have sex with men and co-infection of ameba and HIV-1 is an emerging problem in developed East Asian countries. To characterize the clinical and epidemiological features of invasive amebiasis in HIV-1 patients, the medical records of 170 co-infected cases were analyzed retrospectively, and E. histolytica genotype was assayed in 14 cases. In this series of HIV-1-infected patients, clinical presentation of invasive amebiasis was similar to that described in the normal host. High fever, leukocytosis and high CRP were associated with extraluminal amebic diseases. Two cases died from amebic colitis (resulting in intestinal perforation in one and gastrointestinal bleeding in one), and three cases died from causes unrelated to amebiasis. Treatment with metronidazole or tinidazole was successful in the other 165 cases. Luminal treatment was provided to 83 patients following metronidazole or tinidazole treatment. However, amebiasis recurred in 6 of these, a frequency similar to that seen in patients who did not receive luminal treatment. Recurrence was more frequent in HCV-antibody positive individuals and those who acquired syphilis during the follow-up period. Various genotypes of E. histolytica were identified in 14 patients but there was no correlation between genotype and clinical features. The outcome of metronidazole and tinidazole treatment of uncomplicated amebiasis was excellent even in HIV-1-infected individuals. Luminal treatment following metronidazole or tinidazole treatment does not reduce recurrence of amebiasis in high risk populations probably due to amebic re-infection. PMID:21931875

  9. Draft Genome Sequence of Helicobacter suis Strain SNTW101, Isolated from a Japanese Patient with Nodular Gastritis.

    PubMed

    Matsui, Hidenori; Takahashi, Tetsufumi; Murayama, Somay Y; Uchiyama, Ikuo; Yamaguchi, Katsushi; Shigenobu, Shuji; Suzuki, Masato; Rimbara, Emiko; Shibayama, Keigo; Øverby, Anders; Nakamura, Masahiko

    2016-01-01

    We present here the draft whole-genome shotgun sequence of an uncultivated strain SNTW101 of Helicobacter suis, which has been maintained in the stomachs of mice. This strain was originally isolated from gastric biopsy specimens of a urea breath test-negative Japanese patient suffering from nodular gastritis. PMID:27609915

  10. Novel mutations in the COL2A1 gene in Japanese patients with Stickler syndrome

    PubMed Central

    Kondo, Hiroyuki; Matsushita, Itsuka; Nagata, Tatsuo; Hayashi, Takaaki; Kakinoki, Masashi; Uchio, Eiichi; Kondo, Mineo; Ohji, Masahito; Kusaka, Shunji

    2016-01-01

    Stickler syndrome is an inherited connective tissue disorder that affects the eyes, cartilage and articular tissues. The phenotypes of Stickler syndrome include congenital high myopia, retinal detachment, premature joint degeneration, hearing impairment and craniofacial anomalies, such as cleft palate and midline facial hypoplasia. The disease is genetically heterogeneous, and the majority of the cases are caused by mutations in the COL2A1 gene. We examined 40 Japanese patients with Stickler syndrome from 23 families to determine whether they had mutations in the COL2A1 gene. This analysis was conducted by examining each patient’s genomic DNA by Sanger sequencing. Five nonsense, 4 splicing and 8 deletion mutations in the COL2A1 gene were identified, accounting for 21 of the 23 families. Different mutations of the COL2A1 gene were associated with similar phenotypes but with different degrees of expressivity. PMID:27408751

  11. Analysis of the genes responsible for steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis in Japanese patients by whole-exome sequencing analysis.

    PubMed

    Ogino, Daisuke; Hashimoto, Taeko; Hattori, Motoshi; Sugawara, Noriko; Akioka, Yuko; Tamiya, Gen; Makino, Satoshi; Toyota, Kentaro; Mitsui, Tetsuo; Hayasaka, Kiyoshi

    2016-02-01

    Steroid-resistant nephrotic syndrome (SRNS) represents glomerular disease resulting from a number of different etiologies leading to focal segmental glomerulosclerosis (FSGS). Recently, many genes causing SRNS/FSGS have been identified. These genes encode the proteins associated with the formation and/or maintenance of glomerular filtration barrier. Next-generation sequencing is used to analyze large numbers of genes at lower costs. To identify the genetic background of Japanese patients, we studied 26 disease-causing genes using whole-exome sequencing analysis in 24 patients with SRNS and/or FSGS from 22 different Japanese families. We finally found eight causative gene mutations, four recessive and four dominant gene mutations, including three novel mutations, in six patients from five different families, and one novel predisposing mutation in two patients from two different families. Causative gene mutations have only been identified in ~20% of families and further analysis is necessary to identify the unknown disease-causing gene. Identification of the disease-causing gene would support clinical practices, including the diagnosis, understanding of pathogenesis and treatment. PMID:26467726

  12. Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study

    PubMed Central

    Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Miyasaka, Nobuyuki; Mukai, Masaya; Matsubara, Tsukasa; Uchida, Shoji; Akama, Hideto; Kupper, Hartmut; Arora, Vipin; Tanaka, Yoshiya

    2014-01-01

    Objectives To evaluate the efficacy and safety of adalimumab+methotrexate (MTX) in Japanese patients with early rheumatoid arthritis (RA) who had not previously received MTX or biologics. Methods This randomised, double-blind, placebo-controlled, multicentre study evaluated adalimumab 40 mg every other week+MTX 6–8 mg every week versus MTX 6–8 mg every week alone for 26 weeks in patients with RA (≤2-year duration). The primary endpoint was inhibition of radiographic progression (change (Δ) from baseline in modified total Sharp score (mTSS)) at week 26. Results A total of 171 patients received adalimumab+MTX (mean dose, 6.2±0.8 mg/week) and 163 patients received MTX alone (mean dose, 6.6±0.6 mg/week, p<0.001). The mean RA duration was 0.3 years and 315 (94.3%) had high disease activity (DAS28>5.1). Adalimumab+MTX significantly inhibited radiographic progression at week 26 versus MTX alone (ΔmTSS, 1.5±6.1 vs 2.4±3.2, respectively; p<0.001). Significantly more patients in the adalimumab+MTX group (62.0%) did not show radiographic progression (ΔmTSS≤0.5) versus the MTX alone group (35.4%; p<0.001). Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission, using various definitions, at 26 weeks versus MTX alone. Combination therapy was well tolerated, and no new safety signals were observed. Conclusions Adalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity. PMID:23316080

  13. Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease

    PubMed Central

    Hayashi, Atsuko; Nomura, Hiroshi; Mochizuki, Ruriko; Ohnuma, Ayumu; Kimpara, Teiko; Suzuki, Kyoko; Mori, Etsuro

    2015-01-01

    Background/Aims We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). Methods A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. Results For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. Conclusions The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients. PMID:26483830

  14. Essential content of evidence-based clinical practice guidelines for bladder cancer: The Japanese Urological Association 2015 update.

    PubMed

    Kubota, Yoshinobu; Nakaigawa, Noboru

    2016-08-01

    The Japanese Urological Association revised the clinical practice guidelines for bladder cancer in April 2015. This was the first update carried out in the 6 years since the development of the initial clinical practice guidelines for bladder cancer in 2009. The descriptive content was revised, and additions were made with a focus on new-found evidence and advances in the latest medical practices, and on the basis of the increasingly aging population observed in the underlying social context in Japan. An algorithm for the treatment of bladder cancer has been presented as a new trial. In the present article, we will introduce the essential contents and clinical questions that address the present revisions. PMID:27374472

  15. Microarray and FISH-based genotype-phenotype analysis of 22 Japanese patients with Wolf-Hirschhorn syndrome.

    PubMed

    Shimizu, Kenji; Wakui, Keiko; Kosho, Tomoki; Okamoto, Nobuhiko; Mizuno, Seiji; Itomi, Kazuya; Hattori, Shigeto; Nishio, Kimio; Samura, Osamu; Kobayashi, Yoshiyuki; Kako, Yuko; Arai, Takashi; Tsutomu, Oh-ishi; Kawame, Hiroshi; Narumi, Yoko; Ohashi, Hirofumi; Fukushima, Yoshimitsu

    2014-03-01

    Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome of the distal 4p chromosome, characterized by craniofacial features, growth impairment, intellectual disability, and seizures. Although genotype-phenotype correlation studies have previously been published, several important issues remain to be elucidated including seizure severity. We present detailed clinical and molecular-cytogenetic findings from a microarray and fluorescence in situ hybridization (FISH)-based genotype-phenotype analysis of 22 Japanese WHS patients, the first large non-Western series. 4p deletions were terminal in 20 patients and interstitial in two, with deletion sizes ranging from 2.06 to 29.42 Mb. The new Wolf-Hirschhorn syndrome critical region (WHSCR2) was deleted in all cases, and duplication of other chromosomal regions occurred in four. Complex mosaicism was identified in two cases: two different 4p terminal deletions; a simple 4p terminal deletion and an unbalanced translocation with the same 4p breakpoint. Seizures began in infancy in 33% (2/6) of cases with small (<6 Mb) deletions and in 86% (12/14) of cases with larger deletions (>6 Mb). Status epilepticus occurred in 17% (1/6) with small deletions and in 87% (13/15) with larger deletions. Renal hypoplasia or dysplasia and structural ocular anomalies were more prevalent in those with larger deletions. A new susceptible region for seizure occurrence is suggested between 0.76 and 1.3 Mb from 4 pter, encompassing CTBP1 and CPLX1, and distal to the previously-supposed candidate gene LETM1. The usefulness of bromide therapy for seizures and additional clinical features including hypercholesterolemia are also described. PMID:24357569

  16. Virtual glaucoma clinics: patient acceptance and quality of patient education compared to standard clinics

    PubMed Central

    Court, Jennifer H; Austin, Michael W

    2015-01-01

    Purpose Virtual glaucoma clinics allow rapid, reliable patient assessment but the service should be acceptable to patients and concordance with treatment needs to be maintained with adequate patient education. This study compares experiences and understanding of patients reviewed via the virtual clinic versus the standard clinic by way of an extended patient satisfaction questionnaire (PSQ). Patients and methods One hundred PSQs were given to consecutive patients attending glaucoma clinics in October 2013. All 135 patients reviewed via the virtual clinic from April 2013 until August 2013 were sent postal PSQs in September 2013. Data were obtained for demographics, understanding of glaucoma, their condition, satisfaction with their experience, and quality of information. Responses were analyzed in conjunction with the clinical records. Results Eighty-five percent of clinic patients and 63% of virtual clinic patients responded to the PSQ. The mean satisfaction score was over 4.3/5 in all areas surveyed. Virtual clinic patients’ understanding of their condition was very good, with 95% correctly identifying their diagnosis as glaucoma, 83% as ocular hypertension and 78% as suspects. There was no evidence to support inferior knowledge or self-perceived understanding compared to standard clinic patients. Follow-up patients knew more about glaucoma than new patients. Over 95% of patients found our information leaflet useful. Forty percent of patients sought additional information but less than 20% used the internet for this. Conclusion A substantial proportion of glaucoma pathway patients may be seen by non-medical staff supervised by glaucoma specialists via virtual clinics. Patients are accepting of this format, reporting high levels of satisfaction and non-inferior knowledge to those seen in standard clinics. PMID:25987832

  17. Inflammageing assessed by MMP9 in normal Japanese individuals and the patients with Werner syndrome.

    PubMed

    Goto, Makoto; Chiba, Junji; Matsuura, Masaaki; Iwaki-Egawa, Sachiko; Watanabe, Yasuhiro

    2016-05-01

    Age-associated minor inflammation: inflammageing may explain human ageing mechanism(s). Our previous study reported a significant increase in the serum level of highly sensitive C-reactive protein (hsCRP) with normal ageing and the patients with Werner syndrome (WS). To further study the minor inflammatory condition associated with ageing, another possible ageing biomarker: matrix metalloproteinase-9 (MMP9) was examined in the sera from 217 normal Japanese individuals aged between 1 and 100 years and 41 mutation-proven Japanese WS aged between 32 and 70 years. MMP9 was assayed by ELISA. The serum level of MMP9 was elevated significantly (p < 0.001) with normal ageing from both sexes as hsCRP. In contrast to normal ageing, the serum MMP9 level in WS decreased significantly with calendar age (p < 0.05). The MMP9 level (ng/mL) in WS (147.2 ± 28.5) was not significantly different in comparison with those from age-matched normal adult population aged between 25 and 70 years (109.1 ± 9.4), nor normal elderly population aged between 71 and 100 years (179.9 ± 16.1). Although both normal ageing and WS were associated with minor inflammation, the inflammatory parameters such as serum MMP9 and hsCRP changed differently between normal ageing and WS. The WS-specific chronic inflammation including skin ulcer and diabetes mellitus may contribute the different behavior of both ageing biomarkers from normal ageing. PMID:27195193

  18. Inflammageing assessed by MMP9 in normal Japanese individuals and the patients with Werner syndrome

    PubMed Central

    Goto, Makoto; Chiba, Junji; Matsuura, Masaaki; Iwaki-Egawa, Sachiko; Watanabe, Yasuhiro

    2016-01-01

    Summary Age-associated minor inflammation: inflammageing may explain human ageing mechanism(s). Our previous study reported a significant increase in the serum level of highly sensitive C-reactive protein (hsCRP) with normal ageing and the patients with Werner syndrome (WS). To further study the minor inflammatory condition associated with ageing, another possible ageing biomarker: matrix metalloproteinase-9 (MMP9) was examined in the sera from 217 normal Japanese individuals aged between 1 and 100 years and 41 mutation-proven Japanese WS aged between 32 and 70 years. MMP9 was assayed by ELISA. The serum level of MMP9 was elevated significantly (p < 0.001) with normal ageing from both sexes as hsCRP. In contrast to normal ageing, the serum MMP9 level in WS decreased significantly with calendar age (p < 0.05). The MMP9 level (ng/mL) in WS (147.2 ± 28.5) was not significantly different in comparison with those from age-matched normal adult population aged between 25 and 70 years (109.1 ± 9.4), nor normal elderly population aged between 71 and 100 years (179.9 ± 16.1). Although both normal ageing and WS were associated with minor inflammation, the inflammatory parameters such as serum MMP9 and hsCRP changed differently between normal ageing and WS. The WS-specific chronic inflammation including skin ulcer and diabetes mellitus may contribute the different behavior of both ageing biomarkers from normal ageing. PMID:27195193

  19. 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. PMID:25500922

  20. Safety, tolerability, pharmacokinetics, and pharmacodynamics of exenatide once weekly in Japanese patients with type 2 diabetes.

    PubMed

    Iwamoto, Kazuya; Nasu, Risa; Yamamura, Ayuko; Kothare, Prajakti A; Mace, Kenneth; Wolka, Anne M; Linnebjerg, Helle

    2009-01-01

    This randomized, placebo-controlled, double-blind, parallel study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of exenatide once weekly (QW) in 30 Japanese patients with type 2 diabetes (T2D) suboptimally controlled by diet and exercise alone or combined with biguanide, sulfonylurea, thiazolidinedione, or combinations of these agents (58.6% male; 58+/-9 years; body mass index 26.3+/-2.9 kg/m(2); hemoglobin A(1c) [HbA(1c)] 7.4+/-0.8%; fasting plasma glucose [FPG] 156.1+/-29.1 mg/dL; duration of T2D 6+/-5 years; means +/- SD). Patients were randomized in a 1:1:1 ratio to subcutaneous placebo QW, exenatide QW 0.8 mg, or exenatide QW 2.0 mg for 10 weeks. All evaluable patients were analyzed (placebo QW, n=10; exenatide QW 0.8 mg, n=10; exenatide QW 2.0 mg, n=9), unless otherwise stated. Steady-state plasma exenatide concentrations were observed by Week 8 of the study. For the evaluable pharmacokinetic population, geometric mean (90% confidence interval) steady-state plasma concentrations (pg/mL) were 81.2 (68.3-96.4) and 344.5 (256.5-462.7) with exenatide QW 0.8 mg (n=8) and exenatide QW 2.0 mg (n=5), respectively. Baseline-to-Week 10 glycemic improvements with placebo QW, exenatide QW 0.8 mg, and exenatide QW 2.0 mg, respectively, were: HbA(1c) (%): -0.4+/-0.3, -1.0+/-0.7, and -1.5+/-0.7; FPG (mg/dL): -20.5+/-20.4, -25.2+/-10.9, and -50.8+/-27.8; and 2-hour postprandial plasma glucose excursions (mg/dL): -8.8+/-26.9, -50.0+/-41.1, and -59.7+/-26.8 (means +/- SD). No serious adverse events (AEs) were reported and no AEs led to study discontinuation in any group. The most frequent AE observed was mild-to-moderate injection site induration. No serious hypoglycemia was reported. Exenatide QW for 10 weeks was well tolerated and improved short-term glycemic control in Japanese patients with suboptimally controlled T2D. PMID:19706990

  1. A Qualitative Study of Confusing Experiences among Japanese Adult Patients with Type 1 Diabetes

    PubMed Central

    Nishio, Ikuko; Chujo, Masami; Kataoka, Hideyuki

    2016-01-01

    Background In this study, we investigated the powerlessness of patients with type 1 diabetes (T1D), and described the structure of powerlessness that these individuals experienced. In order for patients to recover from this state, we recommend that they take steps to regain their power. Methods Fifteen Japanese adults with T1D participated in this study. Data were collected from all subjects between July 2013 and March 2014 via in-depth semi-structured interviews. Qualitative data analysis was conducted according to a grounded theory approach. Finally, the core category was identified, which allowed us to build a new powerlessness structure for T1D. Results The results suggested a core category, ‘Wandering a tangled path,’ comprising four categories, eight subcategories, and twenty-six concepts. These four categories were as follows: ‘being burdened by T1D,’ ‘suffering from insulin-related troubles,’ ‘being unable to cope with difficulties in self-management,’ and ‘facing social prejudice.’ In the state of powerlessness, negative emotional experiences snowballed, with patients feeling more and more depressed until they ultimately reached ‘rock bottom.’ Conclusion We found that as negative emotional experiences related to powerlessness increased, negative feelings intensified until the patients reached rock bottom. Powerlessness is like ‘wandering a tangled path,’ a state in which T1D patients struggle to cope with reality on their own when faced with both internal and external events. ‘Wandering a tangled path’ is at the core of powerlessness. A primary characteristic of the structure of powerlessness is suffering from confusing experiences. To help patients cope with T1D without being crushed by powerlessness, nurses must pay attention to signs of powerlessness. Powerlessness is not just an emotional state, but a combination of feelings, perceptions, and thoughts; therefore, it is important to comprehensively understand patients

  2. HLA-DR, DQ and T cell antigen receptor constant beta genes in Japanese patients with ulcerative colitis.

    PubMed Central

    Kobayashi, K; Atoh, M; Konoeda, Y; Yagita, A; Inoko, H; Sekiguchi, S

    1990-01-01

    We studied the T cell antigen receptor (TcR) constant beta chain genes on HLA typed Japanese patients with ulcerative colitis (UC). A TcR constant beta EcoRI 6.0-kb fragment was present in all Japanese UC patients (n = 17) but completely absent in the controls (n = 35) (chi2 = 47.6, P less than 0.001). The frequency of HLA-DR2 antigen was significantly higher in UC patients (85% versus 28% in controls, P less than 0.001). Furthermore, HLA-DQw1 antigen was also increased in UC patients (96% versus 60% in controls, P less than 0.001). However, HLA-DR4 antigen was significantly decreased in UC patients (12% versus 37%, P = 0.02). HLA-DR1 antigen was not found in UC patients and was present in only 15% of the controls. These results suggest that TcR beta chain and HLA-DQw1 antigen may be important in the pathogenesis of Japanese UC. Images Fig. 1 PMID:1973647

  3. [Retrospective Analysis of the Afatinib Clinical Pathway during the 28-Day Introductory Period-The Japanese Style of Collaborative Drug Therapy Management(J-CDTM)].

    PubMed

    Iwata, Kaori; Ryota, Noriko; Hikita, Ami; Sando, Masumi; Suzuki, Hidekazu; Tamiya, Motohiro; Azuma, Yuichiro; Tani, Eriko; Hamaguchi, Masanari; Tanaka, Ayako; Shiroyama, Takayuki; Morishita, Naoko; Okamoto, Norio; Futagami, Sumiko; Hirashima, Tomonori

    2015-08-01

    Afatinib is a newly approved second-generation epidermal growth factor receptor-tyrosine kinase inhibito r(EGFR-TKI). Afatinib has been shown to prolongthe overall survival of patients with non-small cell lungcancer (NSCLC) with EGFR mutations compared with the standard chemotherapy. However, Grade 3 or 4 toxicities, includingdiarrhea, rash, paronychia, and stomatitis, have been observed more frequently in patients treated with afatinib than in those treated with first-generation EGFR-TKIs. Accordingly, our institution developed an afatinib clinical pathway (the afatinib pathway), which was designed by certified nurses, medical physicians, and certified pharmacists, with the goal of reducing the severity of diarrhea and rash that occur most frequently duringthe 28-day introductory period of afatinib treatment. Between May and October 2014, afatinib was administered accordingto the afatinib pathway to 14 patients with NSCLC and EGFR mutations. Of these patients, only one (7.1%) experienced Grade 3 diarrhea. No other patient experienced Grade 3 or 4 toxicity. The afatinib pathway was effective in reducingthe severities of the diarrhea and rash duringthe 28-day introductory period of the afatinib treatment. Our implementation of the afatinib pathway could be considered the Japanese style of collaborative drugtherapy management (J-CDTM). PMID:26321711

  4. Japanese nationwide surveillance in 2011 of antibacterial susceptibility patterns of clinical isolates from complicated urinary tract infection cases.

    PubMed

    Ishikawa, Kiyohito; Hamasuna, Ryoichi; Uehara, Shinya; Yasuda, Mitsuru; Yamamoto, Shingo; Hayami, Hiroshi; Takahashi, Satoshi; Matsumoto, Tetsuro; Minamitani, Shinichi; Kadota, Jun-ichi; Iwata, Satoshi; Kaku, Mitsuo; Watanabe, Akira; Sunakawa, Keisuke; Sato, Junko; Hanaki, Hideaki; Tsukamoto, Taiji; Kiyota, Hiroshi; Egawa, Shin; Deguchi, Takashi; Matsumoto, Minori; Tanaka, Kazushi; Arakawa, Soichi; Fujisawa, Masato; Kumon, Hiromi; Kobayashi, Kanao; Matsubara, Akio; Wakeda, Hironobu; Amemoto, Yoshinosuke; Onodera, Shoichi; Goto, Hirokazu; Komeda, Hisao; Yamashita, Masuo; Takenaka, Tadasu; Fujimoto, Yoshinori; Tsugawa, Masaya; Takahashi, Yoshito; Maeda, Hiroshi; Onishi, Hiroyuki; Ishitoya, Satoshi; Nishimura, Kazuo; Mitsumori, Kenji; Ito, Toru; Togo, Yoshikazu; Nakamura, Ichiro; Ito, Noriyuki; Kanamaru, Sojun; Hirose, Takaoki; Muranaka, Takashi; Yamada, Daisuke; Ishihara, Satoshi; Oka, Hiroya; Inatomi, Hisato; Matsui, Takashi; Kobuke, Makoto; Kunishima, Yasuharu; Kimura, Takahiro; Ichikawa, Takaharu; Kagara, Ichiro; Matsukawa, Masanori; Takahashi, Koichi; Mita, Koji; Kato, Masao; Okumura, Kazuhiro; Kawanishi, Hiroaki; Hashimura, Takayuki; Aoyama, Teruyoshi; Shigeta, Masanobu; Koda, Shuntaro; Taguchi, Keisuke; Matsuda, Yohei

    2015-09-01

    To investigate antimicrobial susceptibility patterns of various bacterial pathogens isolated from complicated urinary tract infection (UTI) cases, the Japanese Society of Chemotherapy, the Japanese Association of Infectious Disease, and the Japanese Society of Clinical Microbiology conducted the second nationwide surveillance from January to September 2011. With the cooperation of 42 medical institutions throughout Japan, 1036 strains belonging to 8 clinically relevant bacterial species were collected. Among methicillin-resistant Staphylococcus aureus (MRSA) strain, the vancomycin (VCM) MIC for 5.5% (3/55) of the strains was 2 μg/mL. Ampicillin, VCM, and linezolid were relatively active against 209 Enterococcus faecalis strains. The proportion of fluoroquinolone (FQ)-resistant strains was >20%. The MIC90 of FQs against the 382 Escherichia coli strains was 2-64 mg/L and the proportion resistant to FQs was approximately 30%. However, susceptibility of E. coli to sitafloxacin was still high (MIC90 = 2 mg/L). Fifty-eight (15.2%) of 382 E. coli, 6 (4.5%) of 132 Klebsiella pneumoniae, 1 (2.4%) of 41 Klebsiella oxytoca and 4 (6.8%) of 59 Proteus mirabilis strains were suspected of producing extended-spectrum beta-lactamase. Of 93 Pseudomonas aeruginosa strains, the proportions resistant to imipenem, amikacin, and ciprofloxacin were 21.5%, 4.3%, and 20.4%, respectively. Four strains (4.3%) were found to be multidrug-resistant. In complicated UTI cases, all of MRSA and E. faecalis were susceptible to all anti-MRSA agents. Sitafloxacin was active against other FQ-resistant E. coli strains. The isolation of extended-spectrum beta-lactamase-producing and multidrug-resistant strains increased. PMID:26166322

  5. Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs

    PubMed Central

    Matsubara, Tsukasa; Urata, Yukitomo; Suematsu, Eiichi; Ohta, Shuji; Honjo, Shigeru; Abe, Tohru; Yamamoto, Ami; Miyasaka, Nobuyuki

    2014-01-01

    Objectives To examine the long-term safety of intravenous (IV) abatacept treatment in Japanese patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) or other conventional or biologic disease-modifying antirheumatic drugs. Methods This Phase III, open-label, long-term study (NCT00484289) comprised Japanese patients with RA who had completed abatacept Phase I or Phase II studies, and new patients intolerant to MTX. Patients from Phase I and Phase II studies received a weight-tiered dosing equivalent of 10 mg/kg abatacept, with MTX at doses up to 8 mg/week; newly enrolled patients received weight-tiered 10 mg/kg abatacept monotherapy. Safety and efficacy were assessed. Results A total of 217 patients (Phase I, n = 13; Phase II, n = 178; newly enrolled, n = 26) were treated with IV abatacept for a mean of 3 years. Serious adverse events occurred in 67/217 (30.9%) patients. Most adverse events were mild or moderate. For all cohorts combined, American College of Rheumatology 20% response rates ranged from 61.3 to 81.8% for as-observed and last observation carried forward analyses over 192 weeks. Following initial response, clinical and functional outcomes were maintained for up to 3 years. Conclusions In Japanese patients with RA, IV abatacept with and without background MTX showed tolerable safety and sustained efficacy over 3 years. PMID:24754273

  6. A randomized, double-blind, placebo-controlled, Phase III study of pazopanib in patients with soft tissue sarcoma: results from the Japanese subgroup

    PubMed Central

    Kawai, Akira; Araki, Nobuhito; Hiraga, Hiroaki; Sugiura, Hideshi; Matsumine, Akihiko; Ozaki, Toshifumi; Ueda, Takafumi; Ishii, Takeshi; Esaki, Taito; Machida, Michiko; Fukasawa, Nobuaki

    2016-01-01

    Objective This analysis of the Japanese subpopulation of the PALETTE Phase III, randomized, placebo-controlled study investigated efficacy and safety of pazopanib in patients with metastatic soft tissue sarcoma after failure of standard chemotherapy. Methods Patients were randomly assigned in a 2:1 ratio to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over. Primary endpoint was progression-free survival. Secondary endpoints included overall survival and overall response rate. Efficacy analysis was by intent-to-treat. Safety was also investigated. Results Forty-seven patients received either pazopanib (n = 31) or placebo (n = 16). Median progression-free survival was 7.0 weeks (95% confidence interval: 4.0–11.7) for placebo and 24.7 weeks (95% confidence interval: 8.6–28.1) for pazopanib (hazard ratio = 0.41 [95% confidence interval: 0.19–0.90]; P = 0.002). Median overall survival was 14.9 months (95% confidence interval: 6.8—not calculable) for placebo and 15.4 months (95% confidence interval: 7.9–28.8) for pazopanib (hazard ratio = 0.87 [95% confidence interval: 0.41–1.83]; P = 0.687). More patients receiving pazopanib experienced best response of stable disease versus placebo. Adverse events were similar to the global population; those leading to dose reduction were more common and mean daily dose was lower in the Japanese population versus the global population (45 vs. 32% and 624.4 vs. 700.4 mg, respectively). Conclusions The efficacy and safety of pazopanib observed in the Japanese subpopulation of PALETTE were similar to those in the global population. Pazopanib is a new treatment option for Japanese patients with metastatic non-adipocytic soft tissue sarcoma after chemotherapy. Clinical trial Registration number NCT00753688; GSK study ID: VEG110727; http://www.gsk-clinicalstudyregister.com/study/VEG110727#ps. PMID:26864131

  7. Prevalence of abdominal migraine and recurrent abdominal pain in a Japanese clinic.

    PubMed

    Hikita, Toshiyuki

    2016-07-01

    Prevalence of abdominal migraine (AM) and recurrent abdominal pain (RAP) was evaluated in patients who visited Hikita Pediatric Clinic between May 2010 and April 2015. Patient data were collected prospectively using a questionnaire. Out of a total of 3611 cases, observed prevalence was 2.44% for repeated abdominal pain over a period of ≥3 months, 1.47% for RAP, and 0.19% for AM. Duration of abdominal pain was longer for AM than for non-AM RAP. Certain clinical features were significantly different between AM and non-AM RAP. No correlations were found among age at onset, frequency of attack, and duration of attack for various types of RAP. It was difficult to determine useful diagnostic criteria for distinguishing between AM and non-AM RAP. They did not appear to be separate disease entities but, instead, lie on a disease spectrum. The present prevalence of AM (0.19%) was lower than that in many previous studies from countries other than Japan. PMID:27460403

  8. Japanese; Japanese Songs.

    ERIC Educational Resources Information Center

    Defense Language Inst., Washington, DC.

    This supplementary textbook for students of Japanese presents a collection of 43 songs--folk songs, nursery songs, lullabies, love songs, wedding songs, graduation songs, the national anthem, drinking songs, school songs, and Christmas carols. With the exception of the carols, the musical scores are presented with their Japanese lyrics. The…

  9. [Clinical experience of primaquine use for treatment of vivax and ovale malaria in Japanese travelers].

    PubMed

    Kobayashi, Taiichiro; Kato, Yasuyuki; Yamauchi, Yuko; Ujiie, Mugen; Takeshita, Nozomi; Mizuno, Yasutaka; Kanagawa, Shuzo; Kano, Shigeyuki; Ohmagari, Norio

    2013-01-01

    Primaquine phosphate has been used to prevent relapse as a radical cure after the acute-phase treatment of vivax and ovale malaria however. Many vivax malaria relapses have been reported following a standard dose of primaquine (15 mg/day for 14 days). A higher dose of primaquine (30 mg/day for 14 days) decreases the relapse rate, and the concomitant risk of gastrointestinal side effects tends to disappear when the drug is administered with food. G6PD deficiency is rare in the Japanese population. Although the relapsed phenomenon is reported globally, the higher dose of primaquine is currently recommended in Japan only for those returning from Southeast Asia or Papua New Guinea. Cases of 18 Japanese, including 13 vivax malaria and 5 ovale malaria, prescribed primaquine at a referral center in Japan, were analyzed retrospectively from 2007-2011. Data on diagnosis, treatment, and outcome were extracted from medical records. Of the 18, 10 with vivax malaria were administered the higher dose of primaquine. We found that only one suffered relapse-a vivax malarial case returning from Brazil and treated with the standard dose of primaquine. No ovale malarial case suffered relapse. None, including the 10 prescribed the higher primaquine dose, experienced any adverse side effects. Based on our findings, we recommend a higher dose of primaquine be used to prevent relapse when treating Japanese suffering from vivax malaria. PMID:23484374

  10. Phase I study of tivantinib in Japanese patients with advanced hepatocellular carcinoma: Distinctive pharmacokinetic profiles from other solid tumors.

    PubMed

    Okusaka, Takuji; Aramaki, Takeshi; Inaba, Yoshitaka; Nakamura, Shinichiro; Morimoto, Manabu; Moriguchi, Michihisa; Sato, Takashi; Ikawa, Yuta; Ikeda, Masafumi; Furuse, Junji

    2015-05-01

    A c-Met inhibitor tivantinib is a candidate anticancer agent for patients with hepatocellular carcinoma (HCC), and CYP2C19 is the key metabolic enzyme for tivantinib. Previous Japanese phase I studies in patients with solid tumors (except HCC) recommend 360 mg twice daily (BID) and 240 mg BID for CYP2C19 extensive metabolizers (EM) and poor metabolizers (PM), respectively. In this study, Japanese patients with HCC in whom sorafenib treatment has failed were enrolled to evaluate the safety, tolerability and pharmacokinetics of oral tivantinib as a single agent. The dose was escalated separately in EM and PM, from 120 mg BID to 240 mg BID, in both capsule and tablet formulations. A total of 28 patients (EM: 21, PM: 7) received tivantinib. At a dose of 120 mg BID, dose-limiting toxicities (DLT) did not develop in 12 EM (capsule: 6, tablet: 6) and 7 PM (capsule: 4, tablet: 3) during the DLT-observation period (for 29 days after first dosing). At this dose, the pharmacokinetic profiles of tivantinib (AUC0-12 and Cmax ) did not remarkably differ between EM and PM. When treated with 240 mg BID, 5 of 9 EM (capsule: 4 of 6, tablet: 1 of 3) developed neutropenia-related DLT accompanying plasma tivantinib concentration higher than expected from the previous studies. Consequently, PM did not receive 240 mg BID. In conclusion, 120 mg BID of tivantinib is recommended among Japanese patients with HCC regardless of CYP2C19 phenotype. PMID:25711511

  11. Lenalidomide and low-dose dexamethasone in Japanese patients with newly diagnosed multiple myeloma: A phase II study.

    PubMed

    Suzuki, Kenshi; Shinagawa, Atsushi; Uchida, Toshiki; Taniwaki, Masafumi; Hirata, Hirokazu; Ishizawa, Kenichi; Matsue, Kosei; Ogawa, Yoshiaki; Shimizu, Takayuki; Otsuka, Maki; Matsumoto, Morio; Iida, Shinsuke; Terui, Yasuhito; Matsumura, Itaru; Ikeda, Takashi; Takezako, Naoki; Ogaki, Yumi; Midorikawa, Shuichi; Houck, Vanessa; Ervin-Haynes, Annette; Chou, Takaaki

    2016-05-01

    In the FIRST trial (MM-020), lenalidomide plus low-dose dexamethasone (Rd) reduced the risk of disease progression or death compared with combination melphalan-prednisone-thalidomide. As the FIRST trial did not include any Japanese patients, the efficacy and safety of continuous treatment with Rd was evaluated in 26 Japanese patients with newly diagnosed multiple myeloma (NDMM) in a single-arm, multicenter, open-label phase II trial (MM-025). Patients received lenalidomide on days 1-21 of each 28-day cycle, with a starting dose of 25 mg/day (dose adjusted for renal impairment), and 40 mg/day dexamethasone (dose adjusted for age) on days 1, 8, 15 and 22 of each 28-day cycle until disease progression or discontinuation for any reason. In the efficacy evaluable population, overall response rate was 87.5%, including 29.2% of patients who achieved a complete response/very good partial response. Median durations of response, progression-free survival and overall survival have not been reached. The most common grade 3-4 adverse events were neutropenia (23%) and anemia (19%). The efficacy and safety of Rd were consistent with data from larger studies, including the FIRST trial, thereby supporting the use of Rd continuous in Japanese patients with NDMM who are ineligible for stem cell transplantation. PMID:26914369

  12. Post-marketing surveillance on the long-term use of dabigatran in Japanese patients with nonvalvular atrial fibrillation: Preliminary report of the J-dabigatran surveillance

    PubMed Central

    Inoue, Hiroshi; Uchiyama, Shinichiro; Atarashi, Hirotsugu; Okumura, Ken; Koretsune, Yukihiro; Yasaka, Masahiro; Yamashita, Takeshi; Ohnishi, Makiko; Yagi, Nobutaka; Fukaya, Taku

    2016-01-01

    Background/aim A post-marketing surveillance (PMS) study is being conducted to investigate the safety and effectiveness of the long-term use of dabigatran etexilate (dabigatran) in Japanese patients with nonvalvular atrial fibrillation (NVAF). Results of an interim analysis of this prospective cohort study including patient characteristics and adverse drug reactions (ADRs) collected up to September 17, 2014 are reported here. Methods Patients with NVAF who began to receive dabigatran for the first time from December 2011 to November 2013 were enrolled at 1042 study sites in Japan. Clinical parameters included patient characteristics, dabigatran dose strength, concomitant medications and outcome events. All outcome events were collected as serious and non-serious adverse events (AEs). ADRs were evaluated in this report. Pre-defined safety events of special interest for intensive survey were serious and non-serious outcome events such as myocardial infarction, as well as the total number of hemorrhage and gastrointestinal disorders. Results A total of 6772 patients were registered. The safety analysis set included 6148 patients; mean age was 70.8±9.9 (SD) years: 2323 patients (37.8%) were aged 75 years or older. Males accounted for 66.8% of the patients. Mean CHADS2 score was 1.8±1.3; the CHADS2 score was 0 in 13.6%, 1 in 31.3%, 2 in 25.9%, 3 in 14.9%, and 4 to 6 in 11.1% of the patients. Of the 6148 patients, 1701 patients (27.7%) were switchers from warfarin and 4407 patients (71.7%) were non-switchers (OAC naïve patients). Treatment adherence was assessed for the first 3 months from the start of treatment for this analysis. Total 5656 patients (92.0%) reported taking dabigatran twice daily (bid) every day according to the label recommendation. During the follow up period [mean duration of follow up: 498±259 days (corresponding to 8386 patient-years)], pre-defined safety events of special interest for intensive survey (reported as serious ADRs) were: myocardial

  13. Systematic review and meta-analysis of Japanese familial Alzheimer's disease and FTDP-17.

    PubMed

    Kasuga, Kensaku; Kikuchi, Masataka; Tokutake, Takayoshi; Nakaya, Akihiro; Tezuka, Toshiyuki; Tsukie, Tamao; Hara, Norikazu; Miyashita, Akinori; Kuwano, Ryozo; Ikeuchi, Takeshi

    2015-05-01

    Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD pedigrees with mutations have been reported in the Japanese population; however, it remains unclear whether the genetic and clinical features of FAD in the Japanese population differ from those in other populations. To address this issue, we conducted a systematic review and meta-analysis of Japanese FAD and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) by literature search. Using this analysis, we identified 39 different PSEN1 mutations in 140 patients, 5 APP mutations in 35 patients and 16 MAPT mutations in 84 patients. There was no PSEN2 mutation among Japanese patients. The age at onset in Japanese FAD patients with PSEN1 mutations was significantly younger than that in patients with APP mutations. Kaplan-Meier analysis revealed that patients with MAPT mutations showed a shorter survival than patients with PSEN1 or APP mutations. Patients with mutations in different genes exhibit characteristic clinical presentations, suggesting that mutations in causative genes may modify the clinical presentations. By collecting and cataloging genetic and clinical information on Japanese FAD and FTDP-17, we developed an original database designated as Japanese Familial Alzheimer's Disease Database, which is accessible at http://alzdb.bri.niigata-u.ac.jp/. PMID:25694106

  14. Mutation spectrum and genotype–phenotype correlation of hearing loss patients caused by SLC26A4 mutations in the Japanese: a large cohort study

    PubMed Central

    Miyagawa, Maiko; Nishio, Shin-ya; Usami, Shin-ichi

    2014-01-01

    Mutations in SLC26A4 cause a broad phenotypic spectrum, from typical Pendred syndrome to nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Identification of these mutations is important for accurate diagnosis, proper medical management and appropriate genetic counseling and requires updated information regarding spectrum, clinical characteristics and genotype–phenotype correlations, based on a large cohort. In 100 patients with bilateral enlarged vestibular aqueduct among 1511 Japanese hearing loss probands registered in our gene bank, goiter data were available for 79, of whom 15 had Pendred syndrome and 64 had nonsyndromic hearing loss. We clarified the mutation spectrum for the SLC26A4 mutations and also summarized hearing levels, progression, fluctuation and existence of genotype–phenotype correlation. SLC26A4 mutations were identified in 82 of the 100 patients (82.0%). Of the Pendred syndrome patients, 93% (14/15) were carriers, as were 77% (49/64) of the nonsyndromic hearing loss patients. Clinical characteristics of patients with SLC26A4 mutations were congenital, fluctuating and progressive hearing loss usually associated with vertigo and/or goiter. We found no genotype–phenotype correlations, indicating that, unlike in the case of GJB2 mutations, the phenotype cannot be predicted from the genotype. Our mutation analysis confirmed the importance of mutations in the SLC26A4 gene among hearing loss patients with enlarged vestibular aqueduct and revealed the mutation spectrum, essential information when performing genetic testing. PMID:24599119

  15. Surgical Outcomes and Correlation of the Copenhagen Neck Functional Disability Scale and Modified Japanese Orthopedic Association Assessment Scales in Patients with Cervical Spondylotic Myelopathy

    PubMed Central

    Azhari, Shirzad; Shazadi, Sohrab; Khayat Kashany, Hamid; Nayeb Aghaei, Hossein; Mohammadi, Hassan Reza

    2016-01-01

    Study Design Cross-sectional. Purpose Clinical outcome study comparing the Copenhagen Neck Functional Disability Scale (CNFDS) and modified Japanese orthopedic association (mJOA) assessment scales in patients with cervical spondylotic myelopathy (CSM). Overview of Literature Comparison of instruments that measure patient-reported outcomes is needed. Methods A cross-sectional analysis was conducted. Ninety five patients with CSM were entered into the study and completed the CNFDS and the mJOA preoperatively and postoperatively. Correlation between the CNFDS and the mJOA was evaluated preoperatively and at the end of follow-up. Responsiveness to change of CNFDS and mJOA was also assessed. Clinical outcomes were also measured with the recovery rate of mJOA score at end of follow-up. Results The mean age of patients was 58.2 (standard deviation, SD=8.7) years. Mean follow-up was 2.1 years (range, 1 to 4 years). The mJOA correlated strongly with the CNFDS score preoperatively and postoperatively (r=–0.81 and –0.82, respectively; p<0.001). The CNFDS and the mJOA were able to detect changes after the surgery (p<0.001). The mean mJOA recovery rate was 51.8% (SD=13.1%). Conclusions Surgery for the treatment of patients with CSM is an efficacious procedure. CNFDS and mJOA scores have a strong correlation in measuring disability among CSM patients. PMID:27340528

  16. “Frequent exacerbator” is a phenotype of poor prognosis in Japanese patients with chronic obstructive pulmonary disease

    PubMed Central

    Tomioka, Ryusuke; Kawayama, Tomotaka; Suetomo, Masashi; Kinoshita, Takashi; Tokunaga, Yoshihisa; Imaoka, Haruki; Matsunaga, Kazuko; Okamoto, Masaki; Hoshino, Tomoaki

    2016-01-01

    Background The prognosis of Japanese patients with COPD who suffer repeated exacerbations is unclear, although Westerners with such episodes have a poor prognosis. Materials and methods We conducted a 1-year prospective observational trial involving 90 Japanese patients with COPD: 58 nonexacerbators, 12 infrequent exacerbators, and 20 frequent exacerbators classified on the basis of exacerbation frequency (zero, one, and two or more exacerbations/year), respectively, during the previous year were observed prospectively for 1 year. The characteristics of frequent exacerbators, the frequency of exacerbation, and the period until the first event were then compared among the groups. Results A total of 78 patients completed the study. Frequent exacerbators had a significantly higher risk of frequent exacerbation in the following year than the case for nonexacerbators (odds ratio [95% confidence interval] 2.94 [1.21–7.17], P=0.0340), but not in comparison with infrequent exacerbators (1.51 [0.49–4.63], P>0.05). The mean annual frequency of exacerbations in the following year was significantly (P=0.0020) higher in the frequent exacerbators (1.4 exacerbations/year) than in the nonexacerbators (0.4), but not in the infrequent exacerbators (0.9, P>0.05). The mean period until the first exacerbation was significantly shorter in the frequent exacerbators than in the infrequent or nonexacerbators (P=0.0012). Independent risk factors for future frequent exacerbation included the presence of gastroesophageal reflux disease, more severe airflow obstruction, and use of inhaled corticosteroids. Conclusion Our present results indicate that Japanese COPD patients suffering frequent exacerbation have a poor prognosis. The characteristics of Japanese and Western COPD patients suffering frequent exacerbation are similar. PMID:26893552

  17. Introducing Optometry Students to Clinical Patient Care.

    ERIC Educational Resources Information Center

    Gable, Eileen M.

    2001-01-01

    Describes the innovative content and structure of an introductory course on clinical patient care at the Illinois College of Optometry. Critiques its success based on student grades and feedback, concluding that it was successful in imparting skills of data analysis but had minimal impact on students' ability to empathize with patients. (EV)

  18. Confirmation of the factorial structure of the Japanese short version of the TEMPS-A in psychiatric patients and general adults

    PubMed Central

    Nakato, Yasuya; Inoue, Takeshi; Nakagawa, Shin; Kitaichi, Yuji; Kameyama, Rie; Wakatsuki, Yumi; Kitagawa, Kan; Omiya, Yuki; Kusumi, Ichiro

    2016-01-01

    Background The Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) is a 110-item questionnaire that assesses five affective temperaments. However, a valid shortened version is desired for large-scale investigations to enhance the compliance of respondents. Methods A confirmatory factor analysis was conducted among 320 psychiatric patients and 61 general adults. The participants completed the Japanese 39-item short version of the TEMPS-A, and a portion of the participants completed the 110-item version. An exploratory factor analysis with the principal factor method and varimax rotation was conducted to identify a more suitable model of the short version of the TEMPS-A. Results The confirmatory factor analysis revealed that the 39-item version exhibited a poor model fit. However, we found that the 18-item version exhibited a firm five-factor structure based on the exploratory factor analysis, and this model exhibited an acceptable model fit. It had good or acceptable internal consistency (Cronbach’s αs: 0.672–0.819). Limitations The majority of the subjects in the present study were patients, and the temperament data may have been affected by psychiatric symptoms. Conclusion A firm five-factor structure was not found in the 39-item short version of the Japanese TEMPS-A. Therefore, an 18-item version was proposed. This new 18-item version of the TEMPS-A might be useful for clinical applications and large-scale investigations. PMID:27601911

  19. BRAF, KIT and NRAS mutations and expression of c-KIT, phosphorylated extracellular signal-regulated kinase and phosphorylated AKT in Japanese melanoma patients.

    PubMed

    Oyama, Satomi; Funasaka, Yoko; Watanabe, Atsushi; Takizawa, Toshihiro; Kawana, Seiji; Saeki, Hidehisa

    2015-05-01

    To clarify the status of gene mutation and activation of growth signal in melanoma of Japanese patients in vivo, we analyzed the mutation of BRAF exon 15, NRAS exon 2, and KIT exons 9, 11, 13, 17 and 18 in melanoma cells obtained by laser capture microdissection, and performed direct sequencing in 20 cases of acral lentiginous melanoma (ALM) and 17 cases of superficial spreading melanoma (SSM). In the study of the mutation of BRAF, pyrosequencing was also done. To examine the cell proliferation signaling, immunohistochemistry for phosphorylated extracellular signal-regulated kinase (pERK), phosphorylated AKT (phosphorylated AKT) and c-KIT was done. The mutation of BRAF p.V600E was detected in 13 cases of ALM (65.0%) and 12 cases of SSM (70.6%). No NRAS mutation was found in all cases. The mutation in exons 9, 11, and 18 of KIT was detected in nine cases. The mutation of BRAF and KIT showed no correlation with clinical stage, lymph node metastasis, tumor thickness, ulceration and histology. pERK and pAKT was observed in small population of melanoma cells and there was no correlation with gene mutation. Our results indicate that the mutations of BRAF and KIT exist in Japanese melanoma patients, however, the cell growth signaling may be regulated by not only these mutated genes, but by other unknown regulatory factors, which may affect the prognosis of melanoma. PMID:25766129

  20. Effect of aspirin cessation before endoscopy in Japanese patients with low-dose-aspirin-associated gastroduodenal mucosal injury

    PubMed Central

    Ito, Yoshitsugu; Noguchi, Seiji; Yamaguchi, Sumiharu; Okaniwa, Noriko; Tanabe, Atsushi; Noda, Hisatsugu; Yanamoto, Kenichiro; Tamura, Yasuhiro; Kondo, Yoshihiro; Masui, Ryuta; Izawa, Shinya; Iida, Akihito; Mizuno, Mari; Ogasawara, Naotaka; Funaki, Yasushi; Kasugai, Kunio

    2013-01-01

    Background The incidence of upper gastrointestinal injury by low-dose aspirin (LDA) has increased. Objective We aimed to clarify the risk factors and prevention strategies associated with LDA-induced gastroduodenal ulcer in Japanese patients. Methods A retrospective study involving 284 LDA users who underwent oesophagogastroduodenoscopy between January and December 2010 were included. We investigated the patients’ clinical characteristics and endoscopic findings. Results Of 284 patients, 29 (10.2%) had gastro and/or duodenal ulcers. Male gender, peptic ulcer history, abdominal symptoms, half-dose proton pump inhibitors (PPIs), complete-dose PPIs, and nonsteroidal anti-inflammatory drugs were significantly associated with LDA-induced gastro and/or duodenal ulcers: odds ratio (95% confidence interval) 3.62 (1.06–12.27), 6.60 (1.84–23.62), 3.06 (1.12–8.40), 0.16 (0.03–0.94), 0.07 (0.01–0.61), and 9.68 (1.64–57.18), respectively. PPI significantly reduced gastric ulcers and/or duodenal ulcers (p = 0.03). The modified Lanza score for gastric mucosal lesion in the LDA cessation group was significantly lower than in the LDA noncessation group (0.53 vs. 1.02; p = 0.008). Conclusions Half-dose PPIs as well as complete-dose PPIs were effective for preventing LDA-induced gastric and/or duodenal ulcers. The cessation of LDA before endoscopy may lead to an underestimation of LDA-induced gastric injury. PMID:24917970

  1. Clinical management of dying patients.

    PubMed Central

    Gavrin, J; Chapman, C R

    1995-01-01

    Dying is universal, and death should be a peaceful time. Myriad comfort measures are available in the last weeks before life ends. Discussions about end-of-life issues often suffer from lack of informed opinion. Palliative care experts have identified specific somatic and psychological sources of distress for dying patients and their loved ones. Pain, shortness of breath, nausea and vomiting, and fear of abandonment contribute substantially to both physical and psychological discomfort toward the end of life. Simple, effective methods exist for relieving those symptoms. Knowledge about the natural events associated with dying and an informed approach to medical and psychological interventions contribute to systematic and successful comfort care. We describe the origin of physical and psychological distress at the end of life and provide strategies for alleviating many of the discomforts. PMID:7571591

  2. A Hospital-based Patient Legal Clinic.

    PubMed

    Bishop, Liz; Shahkhan, Hana; Loff, Bebe

    2016-03-01

    The HeLP Patient Legal Clinic has provided free legal advice to public hospital patients with health-related problems since March 2014. This article reports on the findings of a study of the first six months of HeLP's operation. The study adopted qualitative methods informed by grounded theory and sought to understand patient and social worker experiences of HeLP. Interviews were conducted with 13 patients and 10 next of kin. Focus group discussions were carried out with 19 social workers who referred patients to HeLP. Locating the legal service in the hospital's social work department enabled and expedited access to legal advice; a team-based approach to patient problems emerged that enhanced patient outcomes; and provision of legal advice relieved the anxiety experienced by patients, allowing them to focus better on their health concern. PMID:27323643

  3. [Giant Prostate Carcinoma : A Case Report and Long-Term Outcomes in Japanese Patients].

    PubMed

    Furumido, Jun; Abe, Takashige; Kikuchi, Hiroshi; Miyajima, Naoto; Tsuchiya, Kunihiko; Maruyama, Satoru; Shinohara, Nobuo

    2016-07-01

    A 79-year-old male was referred to the Department of Gastroenterology in our hospital due to a large palpable abdominal mass, with the suspicion of a gastrointestinal stromal tumor. An abdominal computed tomographic (CT) scan revealed a huge mass of 270×208×144 mm which occupied the entire pelvic cavity. Since the specimens obtained by an endoscopic ultrasound-guided fine-needle aspiration via lower intestinal tract revealed a Gleason score 4+4 prostate adenocarcinoma, he was then referred to our department. Prostate specific antigen (PSA) was elevated to 3,087 ng/ml, and positron emission tomography-CT revealed right obturator lymph node metastasis and bone metastasis of the left 5th rib. Degarelix was administered as an androgen deprivation therapy, and the PSA level had decreased to 62.4 ng/ml one month later. At the last follow-up, the PSA level was 0.67 ng/ml and the tumorsize had decreased to 88×83×110 mm. Next, we conducted a follow-up survey by mail of 20 reported Japanese cases of a giant prostate carcinoma, and data on 17 cases were available for analysis. In the total of 18 cases, including the present case, with a median follow-up time of 26 months, the 2-year overall survival rate was 85.7% for patients without metastasis, and 65.6% forthose with metastasis. PMID:27569357

  4. Efficacy and Safety of Axitinib Versus Sorafenib in Metastatic Renal Cell Carcinoma: Subgroup Analysis of Japanese Patients from the Global Randomized Phase 3 AXIS Trial

    PubMed Central

    Ueda, Takeshi; Uemura, Hirotsugu; Tomita, Yoshihiko; Tsukamoto, Taiji; Kanayama, Hiroomi; Shinohara, Nobuo; Tarazi, Jamal; Chen, Connie; Kim, Sinil; Ozono, Seiichiro; Naito, Seiji; Akaza, Hideyuki

    2013-01-01

    Objective Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. The efficacy and safety of axitinib in Japanese patients with metastatic renal cell carcinoma were evaluated. Methods A subgroup analysis was conducted in Japanese patients enrolled in the randomized Phase III trial of axitinib versus sorafenib after failure of one prior systemic therapy for metastatic renal cell carcinoma. Results Twenty-five (of 361) and 29 (of 362) patients randomized to the axitinib and sorafenib arms, respectively, were Japanese and included in this analysis. Median progression-free survival in Japanese patients was 12.1 months (95% confidence interval 8.6 to not estimable) for axitinib and 4.9 months (95% confidence interval 2.8–6.6) for sorafenib (hazard ratio 0.390; 95% confidence interval 0.130–1.173; stratified one-sided P = 0.0401). The objective response rate was 52.0% for axitinib and 3.4% for sorafenib (P = 0.0001). The common all-causality adverse events (all grades) in Japanese patients were dysphonia (68%), hypertension (64%), hand–foot syndrome (64%) and diarrhea (56%) for axitinib, and hand–foot syndrome (86%), hypertension (62%) and diarrhea (52%) for sorafenib. The safety profiles of axitinib and sorafenib in Japanese patients were generally similar to those observed in the overall population, with the exceptions of higher incidences of hypertension, dysphonia, hand–foot syndrome, hypothyroidism and stomatitis. Conclusions Axitinib is efficacious and well tolerated in Japanese patients with previously treated metastatic renal cell carcinoma, consistent with the results in the overall population, providing a new targeted therapy for these Japanese patients. PMID:23630366

  5. Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors.

    PubMed

    Shimizu, Toshio; Seto, Takashi; Hirai, Fumihiko; Takenoyama, Mitsuhiro; Nosaki, Kaname; Tsurutani, Junji; Kaneda, Hiroyasu; Iwasa, Tsutomu; Kawakami, Hisato; Noguchi, Kazuo; Shimamoto, Takashi; Nakagawa, Kazuhiko

    2016-06-01

    Background This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.0, and tumor response was assessed using both RECIST v1.1 and immune-related response criteria (irRC). Full pharmacokinetic sampling was performed during cycle 1. Results Three patients received pembrolizumab at 2.0 mg/kg and seven at 10 mg/kg. No dose-limiting toxicities were observed during cycle 1. Eighty percent of patients experienced drug-related AEs (mostly grade 1 or 2); the most common drug-related AEs were nausea, malaise, pyrexia, and aspartate aminotransferase/alanine transaminase (AST/ALT) elevations (n = 2 each). No drug-related grade 4 or 5 AEs occurred. Immune-related AEs comprised grade 3 ALT elevation (n = 1), grade 3 AST elevation (n = 1), grade 1 pneumonitis (n = 1), and grade 1 thyroid-stimulating hormone elevation (n = 1). The safety and pharmacokinetic profiles of Japanese patients were similar to those previously reported for Caucasian patients. A partial tumor response was observed in one patient with non-small-cell lung cancer (NSCLC) and in one patient with melanoma. Conclusions Pembrolizumab at both 2 and 10 mg/kg Q2W was well tolerated in Japanese patients with advanced solid tumors and showed encouraging anti-tumor activity against melanoma and NSCLC. PMID:27000274

  6. Comparative study of dental cephalometric patterns of Japanese-Brazilian, Caucasian and Mongoloid patients

    PubMed Central

    Sathler, Renata; Pinzan, Arnaldo; Fernandes, Thais Maria Freire; de Almeida, Renato Rodrigues; Henriques, José Fernando Castanha

    2014-01-01

    Introduction The objective of this study was to identify the patterns of dental variables of adolescent Japanese-Brazilian descents with normal occlusion, and also to compare them with a similar Caucasian and Mongoloid sample. Methods Lateral cephalometric radiographs were used to compare the groups: Caucasian (n = 40), Japanese-Brazilian (n = 32) and Mongoloid (n = 33). The statistical tests used were one-way ANOVA and ANCOVA. The cephalometric measurements used followed the analyses of Steiner, Tweed and McNamara Jr. Results Statistical differences (P < 0.05) indicated a smaller interincisal angle and overbite for the Japanese-Brazilian sample, when compared to the Caucasian sample, although with similar values to the Mongoloid group. Conclusion The dental patterns found for the Japanese-Brazilian descents were, in general, more similar to those of the Mongoloid sample. PMID:25279521

  7. Serum C-reactive protein levels in Japanese patients with psoriasis and psoriatic arthritis: Long-term differential effects of biologics.

    PubMed

    Asahina, Akihiko; Umezawa, Yoshinori; Yanaba, Koichi; Nakagawa, Hidemi

    2016-07-01

    Psoriasis has been shown to accompany systemic inflammation. We aimed to examine serum C-reactive protein (CRP) levels in Japanese psoriatic patients, and to elucidate their long-term as well as short-term changes by treatment with different biologics. A retrospective study was conducted in those who initiated and successfully continued the treatment for up to 24 months with either infliximab, adalimumab or ustekinumab, at the psoriasis special clinic of Jikei University School of Medicine. A total of 212 patients were included, 171 with plaque-type psoriasis (PsV) and 41 with psoriatic arthritis (PsA). A statistically significant elevation of CRP values was found in the group with a Psoriasis Area and Severity Index (PASI) of 12 or more compared with the PASI of less than 12 for both PsV and PsA. The CRP-positive patients had a higher proportion of PsA compared with the CRP-negative patients, and they had significantly higher PASI scores. Serum CRP values declined as early as at 3 months after systemic treatment with biologics. Tumor necrosis factor (TNF)-α antagonists did lead to a notable and sustained CRP decline up to 24 months. Infliximab showed rapid decline, while CRP decline by adalimumab treatment was time-dependent. The interleukin-12/23 p40 antagonist, ustekinumab, appeared to be less potent than TNF-α antagonists in stabilizing CRP values at low levels despite good control of cutaneous lesions. In conclusion, serum CRP levels can be used to assess disease severity in Japanese psoriatic patients as a marker of systemic inflammation. TNF-α antagonists may be more beneficial than ustekinumab in this regard. PMID:26704718

  8. [Molecular subgrouping and characterization analysis of medulloblastomas in a cohort of Japanese patients].

    PubMed

    Wataya, Takafumi; Hamasaki, Minoru; Taylor, Michael D

    2015-02-01

    Medulloblastoma is the most common solid malignancy and cause of oncologic death among children. Recent advances in genomic analysis obtained through international large-scale collaborations, Medulloblastoma Advanced Genomics International Consortium(MAGIC), have revealed that medulloblastomas can be classified into at least four distinct subgroups depending on their molecular expression profiles. These studies showed that the prognosis, age distributions, and molecular mechanisms of these subgroups of medulloblastomas completely differ from each other. Here we report the first analysis of molecular subgroups of medulloblastoma in Japanese patients(Shizuoka cohort). Molecular subgroups were predicted for 18 medulloblastomas;and age distributions, radiographic features, and histological characteristics were analyzed. It was predicted that 11% of the medulloblastomas were of the WNT type, 50% of the SHH type, 6% of the group 3 type, and 33% of the group 4 type. The percentage of group 3 type medulloblastomas was smaller than in the MAGIC study, while the percentage of the SHH type was larger. However, age distribution, recurrence-free survival, and overall survival for each group were quite similar to the MAGIC study. In addition, in an imaging study, 78% of patients with medulloblastomas of the SHH type presented tumors in the cerebellar hemispheres. The classical pathohistological hallmarks that may predict medulloblastoma prognosis were mainly seen in tumors of the SHH type. Molecular subgrouping of medulloblastomas could be important in the future, not only for prediction of prognosis, but also for decision making regarding the use of future new treatments such as molecular targeting therapy. The establishment of a public molecular analysis system of medulloblastomas in Japan is greatly desired, and it is currently under development;this database will help establish the molecular diagnosis of medulloblastomas in Japan. PMID:25672552

  9. Measurement of the impact of atopic dermatitis on patients' quality of life: a cross-sectional and longitudinal questionnaire study using the Japanese version of Skindex-16.

    PubMed

    Higaki, Yuko; Kawamoto, Kyoko; Kamo, Toshiko; Ueda, Shu; Arikawa, Junko; Kawashima, Makoto

    2004-12-01

    The impact of atopic dermatitis on patients' quality of life was measured using the Japanese version of Skindex-16 in a cross-sectional and longitudinal questionnaire study. One hundred sixty-two adult patients completed Skindex-16 and were followed-up with a standard medical therapy. Three to six months after the initial testing, 135 (83.3%) of the patients again completed Skindex-16 and also answered a general question about whether their skin condition had improved, remained the same, or become worse. The scores of Skindex-16 of 162 patients with atopic dermatitis were significantly higher than those of patients with isolated lesions, particularly in the Symptoms and Emotions scales. Patients with severe atopic dermatitis showed significantly higher scores in the three scales (Symptoms, Emotions, and Functioning), and there was a significant positive correlation between the severity and the 3-scale scores. After the follow-up period, 78 of 135 patients (57.8%) reported that their skin condition had improved. Forty-six patients (34.1%) reported that their skin condition had remained the same, and 11 (8.1%) became worse. Among the patients who said their dermatitis had improved, the scores of Skindex-16 significantly decreased. On the other hand, patients who reported their dermatitis worse showed an increase in the scores. These findings suggest that Skindex-16 responsively measures the disease severity and clinical change in the estimation of the effects of atopic dermatitis on patients' quality of life. This practical and sensitive, skin-disease specific, quality-of-life instrument is valuable for assessing patients' outcomes, especially their response to therapy, and is useful to understanding and improving the quality of life of patients suffering with atopic dermatitis. PMID:15801261

  10. [Dietary reference intakes of trace elements for Japanese and problems in clinical fields].

    PubMed

    Inoue, Yoshifumi

    2016-07-01

    In the dietary reference intakes, EAR(estimated average requirement), RDA(recommended dietary allowance), AL(adequate intake), DG(tentative dietary goal for preventing life style related diseases) and UL(tolerable upper intake level) of eight types of trace elements (iron: Fe, zinc: Zn, copper: Cu, manganese: Mn, iodine: I, selenium: Se, chromium: Cr, molybdenum: Mo) have been set. However, in the meals of hospitals, only iron of which has been taken into account. The content of these trace elements in the enteral nutrient released after 2000 was determined by considering the content of dietary reference intakes of trace elements for Japanese and considered so not fall into deficiency. However, enteral nutrient must be used considering the content of Zn, Cu and the Zn/Cu ratio, the selenium content, and the route of administration, in order to avoid falling into deficiency. PMID:27455794

  11. Efficacy of fluticasone furoate nasal spray and levocetirizine in patients with Japanese cedar pollinosis subjected to an artificial exposure chamber

    PubMed Central

    Hashiguchi, Kazuhiro; Kanzaki, Sho; Wakabayashi, Ken-ichiro; Tanaka, Nobuaki; Kawashima, Kayoko; Suematsu, Kiyochika; Tokunaga, Shoji; Ogawa, Kaoru; Okubo, Kimihiro

    2013-01-01

    Objective This study investigated the clinical efficacy of a combination therapy of levocetirizine (LCTZ) and fluticasone furoate nasal spray (FFNS), compared with LCTZ monotherapy, for the suppression of seasonal allergic rhinitis (SAR) symptoms induced in an artificial exposure chamber. Methods This study was a single-center, placebo-controlled, randomized, 3-way cross-over comparative study performed in 42 Japanese cedar pollinosis patients. These subjects received (1) LCTZ plus FFNS (combination group), (2) LCTZ plus FFNS placebo (monotherapy group), or (3) LCTZ placebo plus FFNS placebo (placebo group) once on the night prior to exposure, with a 1-week washout period between exposures. Nasal (sneezing, rhinorrhea, nasal congestion, and itchy nose) and ocular (eye itching and tearing) symptoms were recorded every 15 min, and the number of sneezes, nose blowing events, and the amount of nasal secretions were measured during exposure. The primary end-point was the cumulative incidence of SAR symptoms during exposure and the ‘ime to occurrence of symptoms’. The secondary end-points were the total nasal symptom score, the ocular symptom score, the amount of nasal discharge, and the number of sneezes and nose blowing events. Results At all the measurement points, the lowest cumulative incidences for the nasal symptoms were observed in the combination group, followed by the monotherapy and placebo groups. All the subjects in the placebo group developed nasal symptoms within 2 h after pollen exposure, while three and eight subjects in the monotherapy and combination groups, respectively, did not develop any nasal symptoms during exposure. In addition, combination therapy delayed the onset of symptoms. Conclusions The results demonstrated that combination therapy with FFNS and LCTZ significantly suppressed the induced SAR symptoms and delayed the onset of symptoms compared with LCTZ monotherapy and placebo. Although the conditions of the allergen challenge

  12. Clinical significance of visceral adiposity assessed by computed tomography: A Japanese perspective

    PubMed Central

    Ryo, Miwa; Kishida, Ken; Nakamura, Tadashi; Yoshizumi, Tohru; Funahashi, Tohru; Shimomura, Iichiro

    2014-01-01

    Abdominal obesity, rather than total amount of fat, is linked to obesity-related disorders. Visceral adiposity is an important component of obesity-related disorders in Japanese individuals with a mild degree of adiposity compared with Western subjects. In 1983, our group reported techniques for body fat analysis using computed tomography (CT) and established the concept of visceral fat obesity in which intra-abdominal fat accumulation is an important factor in the development of obesity-related complications, such as diabetes, lipid disorders, hypertension and atherosclerosis. Our group also established ideal imaging conditions for determining abdominal fat area at the umbilical level CT scan. Visceral fat area (VFA) measured in a single slice at L4 level correlated significantly with the total abdominal visceral fat volume measured on multislice CT scan. In a large-scale study of a Japanese population, the mean number of obesity-related cardiovascular risk factors (hypertension, low high-density lipoprotein cholesterolemia and/or hypertriglyceridemia, and hyperglycemia) was greater than 1.0 at 100 cm2 of VFA, irrespective of gender, age and body mass index. Our group also demonstrated that reduction of visceral fat accumulation subsequent to voluntary lifestyle modification, “Hokenshido”, correlated with a decrease in the number of obesity-related cardiovascular risk factors. It is important to select the most appropriate subjects from the general population (e.g., non-obese subjects with a cluster of risk factors for the metabolic syndrome) that are most suitable for body weight reduction, with the goal of preventing atherosclerotic cardiovascular diseases. PMID:25071881

  13. Clinical importance of assessment of type 2 diabetes mellitus with visceral obesity. A Japanese perspective.

    PubMed

    Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

    2012-03-01

    Type 2 diabetes mellitus (T2DM) is a complex heterogeneous group of metabolic disorders including hyperglycemia and impaired insulin action and/or insulin secretion. Obesity T2DM has become a serious problem in Japan as in Western countries, with over-eating and physical inactivity. Obese Asians have mild degree of adiposity, compared with Western subjects. Unlike total body fat, body fat distribution, especially excess accumulation of visceral fat, correlates with various diabetogenic, atherogenic, prothrombotic and proinflammatory metabolic abnormalities, which increase the risk of atherosclerotic cardiovascular disease (ACVD). Obese patients with T2DM have poor glycemic control with disordered eating behaviors, and complications of hypertension and dyslipidemia, leading to ACVD. The major therapies in obese T2DM, hyperinsulinemia and low insulin sensitivity, available for weight loss, especially visceral fat reduction, include caloric restriction, physical activity and behavior modification. On the other hand, the major therapies in non-obese T2DM with insufficient insulin secretion, are insulin-secretory agents and injectable insulin. For clinically meaningful prevention/reduction in the rate of future ACVD in T2DM, it may be important to stratify T2DM subjects into those with and without visceral obesity and design specific management protocols for each group. PMID:22309596

  14. Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis

    SciTech Connect

    Kato, Nobuyuki; Hijikata, Makoto; Ootsuyama, Yuko; Nakagawa, Masanori; Ohkoshi, Showgo; Sugimura, Takashi; Shimotohno, Kunitada )

    1990-12-01

    The nucleotide sequence of the Japanese type of hepatitis C virus (HCV-J) genome, consisting of 9413 nucleotides, was determined by analyses of cDNA clones from plasma specimens from Japanese patients with chronic hepatitis. HCV-J genome contains a long open reading frame that can encode a sequence of 3010 amino acid residues. Comparison of HCV-J with the American isolate of HCV showed 22.6% difference in nucleotide sequence and 15.1% difference in amino acid sequence. Thus HCV-J and the American isolate of HCV are probably different subtypes of HCV. The relationship of HCV-J with other animal RNA virus families and the putative organization of the HCV-J genome are discussed.

  15. [Combining clinical pathway and patient education approaches].

    PubMed

    Bonnabel, Laurence; Huteau, Marie-Ève; Filhol, Nathalie; Clottes, Edwige; Massin, Julie; Quenet, François; Stoebner-Delbarre, Anne

    2016-01-01

    The integration of the therapeutic education of the patient into a clinical pathway approach helps to optimise nursing practice. Despite some limits, this method allows the position of the caregiver to evolve, going beyond the required methodological framework. It results in the emergence of several new educational facets which are essential for the patient and enable them to become a player in their own care. PMID:26743372

  16. A phase 1/2 study of carfilzomib in Japanese patients with relapsed and/or refractory multiple myeloma.

    PubMed

    Watanabe, Takashi; Tobinai, Kensei; Matsumoto, Morio; Suzuki, Kenshi; Sunami, Kazutaka; Ishida, Tadao; Ando, Kiyoshi; Chou, Takaaki; Ozaki, Shuji; Taniwaki, Masafumi; Uike, Naokuni; Shibayama, Hirohiko; Hatake, Kiyohiko; Izutsu, Koji; Ishikawa, Takayuki; Shumiya, Yoshihisa; Kashihara, Tomohisa; Iida, Shinsuke

    2016-03-01

    We conducted a phase 1/2 study of single-agent carfilzomib in Japanese patients with relapsed/refractory multiple myeloma. Safety, pharmacokinetics and pharmacodynamics of carfilzomib were examined in phase 1. The primary endpoint in phase 2 was the overall response rate (ORR). Carfilzomib was administered in a twice-weekly, consecutive-day dosing schedule. In Phase 1, doses of 15 or 20 mg/m(2) were administered on this schedule or 20 mg/m(2) on Days 1 and 2 of Cycle 1 and then 27 mg/m(2) in the 20/27 mg/m(2) cohort. Patients had a median of five prior therapies, including bortezomib and an immunomodulatory agent. The dose level did not reach the maximum tolerated dose. The most common adverse events were haematological. Notably, carfilzomib either induced new hypertension (n = 4) or aggravated previously existing hypertension (n = 6) in 10 of 50 patients. Four of the eight patients who previously experienced peripheral neuropathy (PN) experienced a recurrence with carfilzomib use, but no new cases of PN occurred. The ORR of the 20/27 mg/m(2) 40 patient cohort was similar to that in the pivotal US study. The dose was efficacious and tolerable in heavily pre-treated Japanese patients; however, meticulous control of hypertension may be necessary for further carfilzomib use. PMID:26732066

  17. Increased epithelial cadherin expression among Japanese intestinal-type gastric cancers compared with specimens from American patients of European descent.

    PubMed

    Theuer, Charles P; Al-Kuran, Rasha; Akiyama, Yoshiyuki; Okumura, Minoru; Ziogas, Al; Carpenter, Philip M

    2006-04-01

    The different patterns of gastric cancer in the Far East and West have evolved to the extent that it has been suggested that the disease in Japan is biologically less aggressive than in the West. We studied paraffin-embedded, formalin-fixed tissue blocks from Japanese patients and American patients of European descent who had undergone gastrectomy for gastric cancer not involving the gastroesophageal junction. Specimens were staged (T stage), graded (Lauren classification), and biomarker expression (epithelial cadherin [E-cadherin], c-erbB2, Ki67, and p53) was quantified using immunohistochemistry without knowledge of the country of origin. E-cadherin was expressed in 49 per cent of malignant cells from Japanese specimens compared with 27 per cent of malignant cells from American specimens (P = 0.04). The expression of E-cadherin on diffuse cancers from the two countries was similar (34.4 in Japanese vs 41.5 in American, P = 0.92). E-cadherin expression, however, was significantly higher among intestinal cancers from the two countries: 56.3 per cent of cells from intestinal or mixed cancers from Japan (n = 32) expressed E-cadherin compared with 22.2 per cent of American specimens (n = 12; P = 0.008).-c-erbB2 was expressed on a higher proportion of malignant cells from American specimens (30% vs 22%; P = 0.20). E-cadherin expression, a favorable prognostic factor, is more common in Japanese intestinal-type gastric cancer not involving the gastroesophageal junction. If the biology of gastric cancer in the Far East is less aggressive than that in the United States, it is likely that treatments need to be individualized. PMID:16676859

  18. Impact of Patient Sex on Clinical Outcomes

    PubMed Central

    Teitsma, Xavier M.; van der Hoeven, Henk; Tamminga, Rob; de Bie, Rob A.

    2014-01-01

    Background: The Combined Quality Care Anterior Cruciate Ligament registry provides data for clinical research regarding primary anterior cruciate ligament (ACL) surgery. Purpose: To explore the data with regard to the clinical outcomes between sexes after ACL reconstruction in a Dutch population. Study Design: Cohort study; Level of evidence, 3. Methods: Data involving patients diagnosed with an ACL tear and eligible for surgery were recorded. Isokinetic muscle strength, functional muscle performance, and anterior-posterior translation of the knee joint were documented preoperatively and at 3, 6, 9, and 12 months postoperatively. Patients completed the Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm, and Tegner rating scales during each examination using a web-based questionnaire. Results: Approximately 90% of ACL injuries occurred during sport activities. The mean (SD) age at surgery was 28 (11) years for both men and women, and the majority of patients were treated with hamstring tendon autografts (94%). Four percent received bone–patellar tendon–bone autografts, and 2% of the patients received other grafts. Preoperatively, the KOOS, Lysholm, and Tegner scores were significantly higher in males. Twelve months postoperatively, both sexes showed comparable isokinetic strength (P = .336), knee laxity (P = .680), and hop test for distance (P = .122) when comparing the injured with the uninjured side. Self-reported knee function was comparable between sexes as assessed by the KOOS (P = .202), Lysholm (P = .872), and Tegner (P = .767) questionnaires during the 12-month follow-up. Conclusion: One year after ACL surgery, all patients had improved greatly, showing only minor differences between sexes. The male group showed slightly better results when evaluating self-reported knee questionnaires. Comparable outcomes and knee function between sexes can therefore be presumed with patients who are treated with hamstring tendon autografts in a Dutch

  19. A Japanese male patient with 'fibular aplasia, tibial campomelia and oligodactyly': an additional case report.

    PubMed

    Kitaoka, Taichi; Namba, Noriyuki; Kim, Ji Yoo; Kubota, Takuo; Miura, Kohji; Miyoshi, Yoko; Hirai, Haruhiko; Kogo, Mikihiko; Ozono, Keiichi

    2009-07-01

    We report a male infant with FATCO syndrome, an acronym for fibular aplasia, tibial campomelia, and oligosyndactyly. Courtens et al. reported an infant with oligosyndactyly of the left hand, complete absence of the right fibula, bowing of the right tibia, and absence of the right fifth metatarsal and phalanges. They noted 5 patients with similar clinical features, and proposed the FATCO syndrome. Our patient had a left-sided cleft lip, cleft palate, oligosyndactyly of the right hand and bilateral feet, and bilateral anterior bowing of the limbs associated with overlying skin dimpling. Radiographs showed a short angulated tibia with left fibular aplasia and right fibular hypoplasia. We consider our case the 6th patient with FATCO syndrome, and the cleft lip and palate, not reported in the previous 5 patients, may allow us to further understand the development of the extremities and facies. PMID:23926365

  20. Clinical Management of Filovirus-Infected Patients

    PubMed Central

    Clark, Danielle V.; Jahrling, Peter B.; Lawler, James V.

    2012-01-01

    Filovirus infection presents many unique challenges to patient management. Currently no approved treatments are available, and the recommendations for supportive care are not evidence based. The austere clinical settings in which patients often present and the sporadic and at times explosive nature of filovirus outbreaks have effectively limited the information available to evaluate potential management strategies. This review will summarize the management approaches used in filovirus outbreaks and provide recommendations for collecting the information necessary for evaluating and potentially improving patient outcomes in the future. PMID:23170178

  1. Analysis of Hepatitis C Virus Genotype 1b Resistance Variants in Japanese Patients Treated with Paritaprevir-Ritonavir and Ombitasvir

    PubMed Central

    Schnell, Gretja; Tripathi, Rakesh; Beyer, Jill; Reisch, Thomas; Zhang, Xinyan; Setze, Carolyn; Rodrigues, Lino; Burroughs, Margaret; Redman, Rebecca; Chayama, Kazuaki; Kumada, Hiromitsu; Collins, Christine; Pilot-Matias, Tami

    2015-01-01

    Treatment of HCV genotype 1b (GT1b)-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) in studies M12-536 and GIFT-I demonstrated high sustained virologic response (SVR) rates. The virologic failure rate was 3% (13/436) across the two studies. Analyses were conducted to evaluate the impact of baseline resistance-associated variants (RAVs) on treatment outcome and the emergence and persistence of RAVs in patients experiencing virologic failure. Baseline paritaprevir resistance-conferring variants in NS3 were infrequent, while Y93H in NS5A was the most prevalent ombitasvir resistance-conferring variant at baseline. A comparison of baseline prevalence of polymorphisms in Japanese and western patients showed that Q80L and S122G in NS3 and L28M, R30Q, and Y93H in NS5A were significantly more prevalent in Japanese patients. In the GIFT-I study, the prevalence of Y93H in NS5A varied between 13% and 21% depending on the deep-sequencing detection threshold. Among patients with Y93H comprising <1%, 1 to 40%, or >40% of their preexisting viral population, the 24-week SVR (SVR24) rates were >99% (276/277), 93% (38/41), and 76% (25/33), respectively, indicating that the prevalence of Y93H within a patient's viral population is a good predictor of treatment response. The predominant RAVs at the time of virologic failure were D168A/V in NS3 and Y93H alone or in combination with other variants in NS5A. While levels of NS3 RAVs declined over time, NS5A RAVs persisted through posttreatment week 48. Results from these analyses are informative in understanding the resistance profile of an ombitasvir- plus paritaprevir/ritonavir-based regimen in Japanese GT1b-infected patients. PMID:26643326

  2. Worldwide Lineages of Clinical Pneumococci in a Japanese Teaching Hospital Identified by DiversiLab System.

    PubMed

    Kashiwaya, Kiyoshi; Saga, Tomoo; Ishii, Yoshikazu; Sakata, Ryuji; Iwata, Morihiro; Yoshizawa, Sadako; Chang, Bin; Ohnishi, Makoto; Tateda, Kazuhiro

    2016-06-01

    Pneumococcal Molecular Epidemiology Network (PMEN) clones are representatives of worldwide-spreading pathogens. DiversiLab system, a repetitive PCR system, has been proposed as a less labor-and time-intensive genotyping platform alternative to conventional methods. However, the utility and analysis parameters of DiversiLab for identifying worldwide lineages was not established. To evaluate and optimize the performance of DiversiLab for identifying worldwide pneumococcal lineages, we examined 245 consecutive isolates of clinical Streptococcus pneumoniae from all age-group patients at a teaching hospital in Japan. The capsular swelling reaction of all isolates yielded 24 different serotypes. Intensive visual observation (VO) of DiversiLab band pattern difference divided all isolates into 73 clusters. Multilocus sequence typing (MLST) of representative 73 isolates from each VO cluster yielded 51 different STs. Among them, PMEN-related lineages accounted for 63% (46/73). Although the serotype of PMEN-related isolates was identical to that of the original PMEN clone in 70% (32/46), CC156-related PMEN lineages, namely Greece(6B)-22 and Colombia(23F)-26, harbored various capsular types discordant to the original PMEN clones. Regarding automated analysis, genotyping by extended Jaccard (XJ) with a 75% similarity index cutoff (SIC) showed the highest correlation with serotyping (adjusted Rand's coefficient, 0.528). Elevating the SIC for XJ to 85% increased the discriminatory power sufficient for distinguishing two major PMEN-related isolates of Taiwan(19F)-14 and Netherlands(3)-31. These results demonstrated a potential utility of DiversiLab for identifying worldwide lineage of pneumococcus. An optimized parameters of automated analysis should be useful especially for comparison for reference strains by "identification" function of DiversiLab. PMID:27107736

  3. Surface dyslexia in a Japanese patient with semantic dementia: evidence for similarity-based orthography-to-phonology translation.

    PubMed

    Fushimi, Takao; Komori, Kenjiro; Ikeda, Manabu; Patterson, Karalyn; Ijuin, Mutsuo; Tanabe, Hirotaka

    2003-01-01

    We studied the reading performance of a Japanese-speaking patient, TI, with bilateral but asymmetrical (left more than right) temporal-lobe atrophy, severe anomia, and poor word comprehension. Most Japanese kanji characters correspond to several different legitimate pronunciations in different contexts, with varying degrees of correspondence consistency. TI made many errors in reading aloud words that violate statistically typical character-sound correspondences, especially for less common words, but had relatively preserved ability to read aloud strings in which the assignment of the typical pronunciation for each component character yields the correct pronunciation for the whole word. The degree of consistency of character-sound correspondences affected his performance on both words and nonwords in a graded manner. One interpretation is that TI's surface dyslexic reading reflects intact direct computation of phonology from orthography, but without the additional constraint from word meaning that is, in this framework, considered critical for correct pronunciation of lower-frequency words with atypical character-sound correspondences. Another interpretation is that TI's performance reflects partially damaged lexical knowledge of whole-word orthography and phonology, coupled with spared sublexcal knowledge of character-sound correspondence rules. Whichever of these interpretations is preferred, this study offers the most detailed information yet available on the characteristics of surface dyslexia in Japanese. PMID:12887989

  4. Correlation between UGT1A1 polymorphisms and raltegravir plasma trough concentrations in Japanese HIV-1-infected patients.

    PubMed

    Yagura, Hiroki; Watanabe, Dai; Ashida, Misa; Kushida, Hiroyuki; Hirota, Kazuyuki; Ikuma, Motoko; Ogawa, Yoshihiko; Yajima, Keishiro; Kasai, Daisuke; Nishida, Yasuharu; Uehira, Tomoko; Yoshino, Munehiro; Shirasaka, Takuma

    2015-10-01

    Raltegravir (RAL), an HIV integrase inhibitor, is metabolized mainly by UDP-glucuronosyltransferase 1A1 (UGT1A1). Polymorphisms in UGT1A1 may cause alterations in the pharmacodynamics of RAL, which is taken twice daily with no dietary restrictions. We compared the effect of two polymorphic alleles in this gene, UGT1A1*6 and UGT1A1*28 on plasma RAL concentrations in Japanese HIV-1-infected patients. Of 114 Japanese HIV-1-infected patients who received RAL, the frequencies of UGT1A1*6 and UGT1A1*28 were 18% and 13%, respectively. The percentage of homozygotes for UGT1A1*6 and UGT1A1*28 was 6% and 4%, respectively, the percentage of compound heterozygotes for UGT1A1*6 and UGT1A1*28 was 2%, and that of heterozygotes for UGT1A1*6 and UGT1A1*28 was 22% and 17%, respectively. RAL plasma trough concentrations were compared for each polymorphism. Significantly higher levels of RAL were observed with patients who were homozygous for UGT1A1*6 (median: 1.0 μg/mL) than for the normal allele (median: 0.11 μg/mL; p = 0.021). Multivariate logistic regression analysis showed that the presence of one or two alleles of UGT1A1*6 or two alleles of UGT1A1*28 were independent factors associated with high RAL plasma trough concentrations (≥ 0.17 μg/mL). These results indicated that UGT1A1*6 and UGT1A1*28 are both factors influencing the RAL plasma trough concentrations in Japanese HIV-1-infected patients. PMID:26233886

  5. NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD.

    PubMed

    Kakuta, Y; Naito, T; Onodera, M; Kuroha, M; Kimura, T; Shiga, H; Endo, K; Negoro, K; Kinouchi, Y; Shimosegawa, T

    2016-06-01

    The efficacy of thiopurines, including azathioprine (AZA) and 6-mercaptopurine (6MP), has been demonstrated for the treatment of inflammatory bowel disease (IBD). The most common and serious adverse event of treatment with thiopurines altered by doctors is leukopenia. Hair loss is also a serious event that could be a critical reason for patients to decline thiopurine treatment. Thiopurine-induced severe hair loss causes cosmetic problems, and it takes a long time to recover. In a recent study, NUDT15 R139C was strongly associated with thiopurine-induced leukopenia in Korean and Caucasian populations. In this study, we performed an association study to investigate and replicate the association of R139C with adverse events of thiopurines in Japanese patients. A total of 142 Japanese patients with IBD, with histories of thiopurine treatment, were examined. NUDT15 R139C was genotyped using a custom TaqMan genotyping assay. Adverse events including leukopenia were reviewed from medical records. The 6MP dose was adjusted to AZA equivalents by multiplying with 2 as a thiopurine dose. Five patients developed severe hair loss and all of them were risk homozygous (T/T) for R139C. No early severe hair loss was observed in patients with the C/T or C/C genotype (P=3.82 × 10(-16), odds ratio=212). The association of R139C with early (<8 weeks) leukopenia (white blood cells<3000 mm(-3)), which was previously reported in Korean patients, was replicated in our Japanese IBD cohort (P=1.92 × 10(-16), odds ratio=28.4). However, we could not confirm the association with late leukopenia in the Japanese subjects. Patients with the C/T genotype discontinued treatment or required thiopurine dose reduction significantly earlier than patients with the C/C genotype (P=1.45 × 10(-4)); however, on manipulating the doses, there was no significant difference in the thiopurine continuation rates between the groups. In the maintenance period, the frequencies of 6MP usage were higher, and the

  6. Clinical diagnosis of hyposalivation in hospitalized patients

    PubMed Central

    BERTI-COUTO, Soraya de Azambuja; COUTO-SOUZA, Paulo Henrique; JACOBS, Reinhilde; NACKAERTS, Olivia; RUBIRA-BULLEN, Izabel Regina Fischer; WESTPHALEN, Fernando Henrique; MOYSÉS, Samuel Jorge; IGNÁCIO, Sérgio Aparecido; da COSTA, Maitê Barroso; TOLAZZI, Ana Lúcia

    2012-01-01

    Objective The aim of this study was to evaluate the effectiveness of clinical criteria for the diagnosis of hyposalivation in hospitalized patients. Material and Methods A clinical study was carried out on 145 subjects (48 males; 97 females; aged 20 to 90 years). Each subject was clinically examined, in the morning and in the afternoon, along 1 day. A focused anamnesis allowed identifying symptoms of hyposalivation, like xerostomia complaints (considered as a reference symptom), chewing difficulty, dysphagia and increased frequency of liquid intake. Afterwards, dryness of the mucosa of the cheecks and floor of the mouth, as well as salivary secretion during parotid gland stimulation were assessed during oral examination. Results Results obtained with Chi-square tests showed that 71 patients (48.9%) presented xerostomia complaints, with a significant correlation with all hyposalivation symptoms (p<0.05). Furthermore, xerostomia was also significantly correlated with all data obtained during oral examination in both periods of evaluation (p<0.05). Conclusion Clinical diagnosis of hyposalivation in hospitalized patients is feasible and can provide an immediate and appropriate therapy avoiding further problems and improving their quality of life. PMID:22666830

  7. Safety and Effectiveness of Endovenous Laser Ablation Combined With Ligation for Severe Saphenous Varicose Veins in Japanese Patients.

    PubMed

    Izumi, Masafumi; Ikeda, Yuichi; Yamashita, Hiroharu; Asaoka, Yoshinari; Fujishiro, Mitsuhiro; Shin, Masahiro; Abo, Yoshihisa

    2016-01-01

    Endovenous laser ablation (EVLA), which is a relatively new therapeutic option for saphenous varicose veins of the legs, is less invasive than conventional stripping surgery with ligation. In this study, we evaluated the safety and effectiveness of EVLA combined with ligation for severe saphenous varicose veins that were graded as ≥ C4 by the CEAP classification. We treated 119 Japanese patients (141 limbs) between July 2005 and December 2007 utilizing a 1320-nm Nd:YAG laser. The obliteration rate of the treated veins was found to be 100% over the entire follow-up period (2.5 years). Consistent with this finding, all of the patients exhibited improved skin lesions (ie, skin pigmentation and ulceration). No major complications, including deep vein thrombosis (DVT) and nerve injury, were observed. A questionnaire survey with a reasonable response rate (66.4%) demonstrated that subjective symptoms and minor complications that were initially observed after EVLA, such as mild pain, numbness, indurations, and localized hot flashes, were remarkably improved by the end of the follow-up period. Furthermore, high levels of patient satisfaction were noted. Thus, EVLA combined with ligation constituted a safe and effective strategy for treating severe saphenous varicose veins in Japanese patients. PMID:26742879

  8. A Retrospective Study of G-Tube Use in Japanese Patients Treated with Concurrent Chemoradiotherapy for Hypopharyngeal Cancer

    PubMed Central

    Homma, Akihiro; Hatakeyama, Hiromitsu; Mizumachi, Takatsugu; Kano, Satoshi; Sakashita, Tomohiro; Kuramoto, Rinnosuke; Nakamaru, Yuji; Onimaru, Rikiya; Tsuchiya, Kazuhiko; Yoshida, Daisuke; Yasuda, Koichi; Shirato, Hiroki; Fukuda, Satoshi

    2016-01-01

    Objective Late toxicity after concurrent chemoradiotherapy (CCRT), such as dysphagia, in patients with squamous cell carcinoma of the head and neck has received a good deal of attention recently. The gastrostomy tube (G-tube) dependence rate 1 year after CCRT was reported to be 16.7–42.9% in Western countries. We evaluated swallowing outcomes after CCRT in patients with hypopharyngeal cancer (HPC) treated in our hospital and compared them with previous reports. Methods We reviewed 96 consecutive patients with a HPC treated by radiotherapy with intravenous or intra-arterial chemotherapy between 2006 and 2013 at Hokkaido University Hospital, Sapporo, Japan. Results At 1 month after CCRT, 13 patients (13.7%) used a G-tube, whereas 5/91 (5.5%) and 4/81 (4.9%) used a G-tube at 3 and 6 months, respectively. Two patients used a G-tube at 12 and 24 months after CCRT (G-tube use rate: 2.8% at 12 months, and 3.2% at 24 months). The variables female, posterior wall primary, stage IV, ECOG performance status of 2, and smoking status were significantly associated with G-tube use at 12 months after CCRT, whereas the route of cisplatin administration was not related to G-tube use (p = 0.303). Conclusions The G-tube use rate up to 1year could be lower in Japanese patients than in Western patients according to previous reports. In particular, Japanese patients resume oral intake sooner than Western patients. Further study of the incidence of dysphagia after CCRT by ethnicity is required to clarify the differences in dysphagia after CCRT. PMID:27556279

  9. Clinical efficacy and tolerability of two Japanese traditional herbal medicines, Hachimi-jio-gan and Gosha-jinki-gan, for lower urinary tract symptoms with cold sensitivity

    PubMed Central

    Yagi, Hiroshi; Sato, Ryo; Nishio, Kojiro; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

    2015-01-01

    We evaluated the efficacy and tolerability of Hachimi-jio-gan (HJG; 八味地黃丸 bā wèi dì huáng wán) and Gosha-jinki-gan (GJG; 濟生腎氣丸 jì shēng shèn qì wán), two traditional Japanese medicines, in 60 patients with lower urinary tract symptoms (LUTS) having cold sensitivity unresponsive to α1-blockers or antimuscarinic drugs. All patients received a mixture of HJG or GJG for 12 weeks in addition to α1-blockers or antimuscarinic drugs as add-on therapy. International Prostate Symptom Score, International Prostate Symptom Score–Quality of Life, Benign Prostatic Hyperplasia Impact Index, and the number of nocturnal voids were statistically much improved. However, there was no change in maximal urinary flow rate and post-void residual urine. Urinary 8-hydroxy-2-deoxyguanosine was statistically greatly improved from baseline after treatment in the HJG group compared to the GJG group. Adverse reactions were observed in 8.3% of patients, but all reactions were mild. Both HJG and GJG mixtures can serve as safe and effective potential therapeutic alternatives in patients with LUTS and cold sensitivity unresponsive to α1-blockers or antimuscarinic drugs. Additionally, HJG mixture was found to have anti-oxidative activity, and therefore further long-term clinical investigations are needed to examine its anti-aging effects in addition to its effect on urinary symptoms. PMID:26587398

  10. Psychometric Properties of the Japanese Version of the STarT Back Tool in Patients with Low Back Pain

    PubMed Central

    Matsudaira, Ko; Oka, Hiroyuki; Kikuchi, Norimasa; Haga, Yuri; Sawada, Takayuki; Tanaka, Sakae

    2016-01-01

    Background and Objective The STarT Back Tool uses prognostic indicators to classify patients with low back pain into three risk groups to guide early secondary prevention in primary care. The present study aimed to evaluate the psychometric properties of the Japanese version of the tool (STarT-J). Methods An online survey was conducted among Japanese patients with low back pain aged 20–64 years. Reliability was assessed by examining the internal consistency of the overall and psychosocial subscales using Cronbach’s alpha coefficients. Spearman’s correlation coefficients were used to evaluate the concurrent validity between the STarT-J total score/psychosocial subscore and standard reference questionnaires. Discriminant validity was evaluated by calculating the area under the curves (AUCs) for the total and psychosocial subscale scores against standard reference cases. Known-groups validity was assessed by examining the relationship between low back pain-related disability and STarT-J scores. Results The analysis included data for 2000 Japanese patients with low back pain; the mean (standard deviation [SD]) age was 47.7 (9.3) years, and 54.1% were male. The mean (SD) STarT-J score was 2.2 (2.1). The Cronbach’s alpha coefficient was 0.75 for the overall scale and 0.66 for the psychosocial subscale. Spearman’s correlation coefficients ranged from 0.30 to 0.59, demonstrating moderate to strong concurrent validity. The AUCs for the total score ranged from 0.65 to 0.83, mostly demonstrating acceptable discriminative ability. For known-groups validity, participants with more somatic symptoms had higher total scores. Those in higher STarT-J risk groups had experienced more low back pain-related absences. Conclusions The overall STarT-J scale was internally consistent and had acceptable concurrent, discriminant, and known-groups validity. The STarT-J can be used with Japanese patients with low back pain. PMID:27002823

  11. Lack of differences in the pharmacokinetics of sepantronium bromide (YM155) between US and Japanese patients with advanced solid tumors or non-Hodgkin lymphoma.

    PubMed

    Aoyama, Yumiko; Katashima, Masataka; Sawamoto, Taiji

    2013-03-01

    The analysis was designed to compare the pharmacokinetics (PK) of sepantronium between US and Japanese patient populations using data obtained from two phase 1 studies being conducted in a similar design, one conducted in the USA and the other in Japan. Patients with a confirmed advanced solid tumor or non-Hodgkin lymphoma (NHL) (US only) that were refractory to standard therapy or for which no standard therapy was available participated in these studies. Sepantronium bromide was administered as a continuous intravenous infusion for 168 h (7 days) every 21 days. During the first two treatment cycles, serial blood and urine samples were collected for up to 48 h after termination of sepantronium bromide infusion. Forty-one subjects in the US study (including five patients with NHL) and 33 patients in the Japanese study were enrolled in both studies and 35 in US and 32 in Japan had adequate samples for PK evaluation. The PK parameters were calculated by non-compartment analysis method and were compared in the US and Japanese populations. The geometric mean ratios (90% confidence intervals) of area under the concentration-time curve, steady state concentration and amount excreted into urine between Japanese and US populations were 1.068 (0.932-1.224), 1.141 (0.996-1.307) and 0.981 (0.855-1.125), respectively. There appear to be no PK differences between the US and Japanese patients with solid tumors or NHL. PMID:23138529

  12. [Clinical Handling of Patients with Dissociative Disorders].

    PubMed

    Okano, Kenichiro

    2015-01-01

    This paper discusses the way informed psychiatrists are expected to handle dissociative patients in clinical situations, with a specific focus on dissociative identity disorders and dissociative fugue. On the initial interview with dissociative patients, information on their history of trauma and any nascent dissociative symptoms in their childhood should be carefully obtained. Their level of stress in their current life should also be assessed in order to understand their symptomatology, as well as to predict their future clinical course. A psychoeducational approach is crucial; it might be helpful to give information on dissociative disorder to these patients as well as their family members in order to promote their adherence to treatment. Regarding the symptomatology of dissociative disorders, detailed symptoms and the general clinical course are presented. It was stressed that dissociative identity disorder and dissociative fugue, the most high-profile dissociative disorders, are essentially different in their etiology and clinical presentation. Dissociative disorders are often confused with and misdiagnosed as psychotic disorders, such as schizophrenia. Other conditions considered in terms of the differential diagnosis include borderline personality disorder as well as temporal lobe epilepsy. Lastly, the therapeutic approach to dissociative identity disorder is discussed. Each dissociative identity should be understood as potentially representing some traumatically stressful event in the past. The therapist should be careful not to excessively promote the creation or elaboration of any dissociative identities. Three stages are proposed in the individual psychotherapeutic process. In the initial stage, a secure environment and stabilization of symptoms should be sought. The second stage consists of aiding the "host" personality to make use of other more adaptive coping skills in their life. The third stage involves coaching as well as continuous awareness of

  13. Establishment and molecular characterization of cell lines from Japanese patients with malignant pleural mesothelioma

    PubMed Central

    SUZAWA, KEN; YAMAMOTO, HIROMASA; MURAKAMI, TOMOYUKI; KATAYAMA, HIDEKI; FURUKAWA, MASASHI; SHIEN, KAZUHIKO; HASHIDA, SHINSUKE; OKABE, KAZUNORI; AOE, KEISUKE; SOH, JUNICHI; ASANO, HIROAKI; TSUKUDA, KAZUNORI; MIMURA, YUSUKE; TOYOOKA, SHINICHI; MIYOSHI, SHINICHIRO

    2016-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive disease that is resistant to conventional therapies. Cell lines are useful models for studying the biological characteristics of tumors; therefore, the establishment of MPM cell lines is valuable for exploring novel therapeutic strategies for MPM. In the present study, 4 MPM cell lines (YUMC8, YUMC44, YUMC63, and YUMC64) were established, which consisted of 2 epithelioid and 2 sarcomatoid mesothelioma histological subtypes, from Japanese patients with MPM. The DNA methylation status, mutations, copy number gains, protein expression of representative genes, and the sensitivity to several drugs were examined in these 4 cell lines. Methylation of P16 was demonstrated in 3/4 cell lines, in which the protein expression of p16 was lost. Methylation of RASSF1A was observed in 3/4 cell lines. Copy number gains of EGFR, HER2 or MET were not detected in the 4 cell lines. Mutations in various genes, including EGFR, KRAS, HER2, BRAF, and PIK3CA, which are frequently detected in non-small cell lung cancer, were not detected in the 4 cell lines. microRNA-34b/c is a direct transcriptional target of p53 and is often silenced in MPM by promoter methylation. In the present study, miR-34b/c was heavily methylated in 2/4 established MPM cell lines. For cell adhesion molecules, E-cadherin expression was detected in the 2 epithelioid MPM cell lines, whereas N-cadherin expression was detected in all 4 established cell lines by western blotting. Vimentin was strongly expressed in the 2 sarcomatoid MPM cell lines. None of the established MPM cell lines demonstrated significant responses to the drugs tested, including NVP-AUY922, 17-DMAG, Trichostatin A, and Vorinostat. Although novel molecular findings were not observed in the current characterization of these MPM cell lines, these lines will be useful for future extensive analyses of the biological behavior of MPM and the development of novel therapeutic strategies. PMID:26870271

  14. Gender, low Kt/V, and mortality in Japanese hemodialysis patients: opportunities for improvement through modifiable practices.

    PubMed

    Kimata, Naoki; Karaboyas, Angelo; Bieber, Brian A; Pisoni, Ronald L; Morgenstern, Hal; Gillespie, Brenda W; Saito, Akira; Akizawa, Tadao; Fukuhara, Shunichi; Robinson, Bruce M; Port, Friedrich K; Akiba, Takashi

    2014-07-01

    Guidelines have recommended single pool Kt/V > 1.2 as the minimum dose for chronic hemodialysis (HD) patients on thrice weekly HD. The Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown that "low Kt/V" (<1.2) is more prevalent in Japan than many other countries, though survival is longer in Japan. We examined trends in low Kt/V, dialysis practices associated with low Kt/V, and associations between Kt/V and mortality overall and by gender in Japanese dialysis patients. We analyzed 5784 HD patients from Japan DOPPS (1999-2011), restricted to patients dialyzing for >1 year and receiving thrice weekly dialysis. Logistic regression models estimated the relationships of patient characteristics with Kt/V. Logistic models also were used to estimate the proportion of low Kt/V cases attributable to various treatment practices. Multivariable Cox regression was used to estimate the associations of low Kt/V, blood flow rate (BFR), and treatment time (TT), with all-cause mortality. From 1999 to 2009, the prevalence of low Kt/V declined in men (37-27%) and women (15-10%). BFR <200 mL/min, TT <240 minutes, and dialyzate flow rate (DFR) < 500 mL/min were common (35, 13, and 19% of patients, respectively) and strongly associated with low Kt/V. Fifteen percent of low Kt/V cases were attributable to BFR <200 and 13% to TT <240, compared to only 3% for DFR <500. Lower Kt/V was associated with elevated mortality, more so among women (hazard ratio [HR] = 1.13 per 0.1 lower Kt/V, 95% CI: 1.07-1.20) than among men (HR = 1.06 per 0.1 lower Kt/V, 95% CI: 1.00-1.12). The relatively large proportion of low Kt/V cases in Japanese facilities may potentially be reduced 30% by increasing BFR to 200 mL/min and TT to 4 hours thrice weekly in HD patients. Associations of low Kt/V with elevated mortality suggest that modification of these practices may further improve survival for Japanese HD patients. PMID:24612374

  15. Enhanced international prognostic index in Japanese patients with diffuse large B-cell lymphoma.

    PubMed

    Nakaya, Aya; Fujita, Shinya; Satake, Atsushi; Nakanishi, Takahisa; Azuma, Yoshiko; Tsubokura, Yukie; Hotta, Masaaki; Yoshimura, Hideaki; Ishii, Kazuyoshi; Ito, Tomoki; Nomura, Shosaku

    2016-01-01

    To evaluate the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI), we analyzed 284 patients treated with the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in our institution in Japan. Their 5-year overall survival (OS) by risk level was 80.7%, 74.8%, 55.4% and 67.5% (P=0.005); and their 5-year progression-free survival (PFS) was 76.8%, 78.6%, 63.7% and 58.3% (P=0.0722). The NCCN-IPI is a simple scale that uses conventional clinical factors, but did not reflect survival in our cohort. The NCCN-IPI may require further evaluation for different regions and ethnicities before adopting it for routine clinical use. PMID:27489766

  16. A novel frameshift mutation of CHD7 in a Japanese patient with CHARGE syndrome

    PubMed Central

    Kohmoto, Tomohiro; Shono, Miki; Naruto, Takuya; Watanabe, Miki; Suga, Ken-ichi; Nakagawa, Ryuji; Kagami, Shoji; Masuda, Kiyoshi; Imoto, Issei

    2016-01-01

    CHARGE syndrome is a rare autosomal dominant developmental disorder involving multiple organs. CHD7 is a major causative gene of CHARGE syndrome. We performed targeted-exome sequencing using a next-generation sequencer for molecular diagnosis of a 4-month-old male patient who was clinically suspected to have CHARGE syndrome, and report a novel monoallelic mutation in CHD7, NM_017780.3(CHD7_v001):c.2966del causing a reading frameshift [p.(Cys989Serfs*3)]. PMID:27081570

  17. Clinical service desires of medical cannabis patients

    PubMed Central

    2012-01-01

    Background Medical cannabis dispensaries following the social or hybrid model offer supplementary holistic services in addition to dispensing medical cannabis. Historically, alternative physical health services have been the norm for these dispensaries, including services such as yoga, acupuncture, or chiropractor visits. A clinical service dearth remains for medical cannabis patients seeking substance use, misuse, dependence, and mental health services. This study examined patient desires for various clinical services and level of willingness to participate in specific clinical services. Methods Anonymous survey data (N = 303) were collected at Harborside Health Center (HHC), a medical cannabis dispensary in Oakland, CA. The sample was 70% male, 48% Caucasian and 21% African American. The mean male age was 38 years old and female mean age was 30. Sixty two percent of the male participants and 44% of the female participants are single. Sixteen percent of the population reported having a domestic partner. Forty six percent of the participants are employed full time, 41% have completed at least some college, and 49% make less than $40,000 a year. Results A significant portion of the sample, 62%, indicated a desire to participate in free clinical services at HHC, 34% would like more information about substances and use, and 41% want to learn more about reducing harms from substance use. About one quarter of the participants marked "would" or "likely would" participate in individual services such as consultation. Approximately 20% indicated "would" or "likely would" participate in psycho-educational forums, harm reduction information sharing sessions, online support groups, and coping, life, and social skills group. There was little interest in traditional NA/AA 12-step groups or adapted 12-step groups. Conclusions Desired clinical services can be qualified as a combination of harm reduction, educational, skills-based, peer support and therapeutic individual and group

  18. Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction.

    PubMed

    Ito, Sadayoshi; Satoh, Minoru; Tamaki, Yuko; Gotou, Hiromi; Charney, Alan; Okino, Naoko; Akahori, Mizuki; Zhang, Jack

    2015-04-01

    This 8-week, multi-center, open-label study assessed the safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction. Patients (n=32) with mean sitting systolic blood pressure (msSBP) ⩾140 mm Hg (after a 2-5-week washout of previous antihypertensive medications) and estimated glomerular filtration rate (eGFR) ⩾15 and <60 ml min(-1) 1.73 m(-2) received LCZ696 100 mg with an optional titration to 200 and 400 mg in a sequential manner starting from Week 2 in patients with inadequate BP control (msSBP ⩾130 mm Hg and mean sitting diastolic blood pressure (msDBP) ⩾80 mm Hg) and without safety concerns. Safety was assessed by monitoring and recording all adverse events (AEs) and change in potassium and creatinine. Efficacy was assessed as change from baseline in msSBP/msDBP. The mean baseline BP was 151.6/86.9 mm Hg, urinary albumin/creatinine ratio (UACR) geometric mean was 7.3 mg mmol(-1) and eGFR was ⩾30 and <60 in 25 (78.1%) patients and was ⩾15 and <30 in 7 (21.9%) patients. Fourteen (43.8%) patients reported at least one AE, which were mild in severity. No severe AEs or deaths were reported. There were no clinically meaningful changes in creatinine, potassium, blood urea nitrogen and eGFR. The geometric mean reduction in UACR was 15.1%, and the mean reduction in msSBP and msDBP was 20.5±11.3 and 8.3±6.3 mm Hg, respectively, from baseline to Week 8 end point. LCZ696 was generally safe and well tolerated and showed effective BP reduction in Japanese patients with hypertension and renal dysfunction without a decline in renal function. PMID:25693859

  19. Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction

    PubMed Central

    Ito, Sadayoshi; Satoh, Minoru; Tamaki, Yuko; Gotou, Hiromi; Charney, Alan; Okino, Naoko; Akahori, Mizuki; Zhang, Jack

    2015-01-01

    This 8-week, multi-center, open-label study assessed the safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction. Patients (n=32) with mean sitting systolic blood pressure (msSBP) ⩾140 mm Hg (after a 2–5-week washout of previous antihypertensive medications) and estimated glomerular filtration rate (eGFR) ⩾15 and <60 ml min−1 1.73 m−2 received LCZ696 100 mg with an optional titration to 200 and 400 mg in a sequential manner starting from Week 2 in patients with inadequate BP control (msSBP ⩾130 mm Hg and mean sitting diastolic blood pressure (msDBP) ⩾80 mm Hg) and without safety concerns. Safety was assessed by monitoring and recording all adverse events (AEs) and change in potassium and creatinine. Efficacy was assessed as change from baseline in msSBP/msDBP. The mean baseline BP was 151.6/86.9 mm Hg, urinary albumin/creatinine ratio (UACR) geometric mean was 7.3 mg mmol−1 and eGFR was ⩾30 and <60 in 25 (78.1%) patients and was ⩾15 and <30 in 7 (21.9%) patients. Fourteen (43.8%) patients reported at least one AE, which were mild in severity. No severe AEs or deaths were reported. There were no clinically meaningful changes in creatinine, potassium, blood urea nitrogen and eGFR. The geometric mean reduction in UACR was 15.1%, and the mean reduction in msSBP and msDBP was 20.5±11.3 and 8.3±6.3 mm Hg, respectively, from baseline to Week 8 end point. LCZ696 was generally safe and well tolerated and showed effective BP reduction in Japanese patients with hypertension and renal dysfunction without a decline in renal function. PMID:25693859

  20. A Phase 3 Study of Evolocumab (AMG 145) in Statin-Treated Japanese Patients at High Cardiovascular Risk.

    PubMed

    Kiyosue, Arihiro; Honarpour, Narimon; Kurtz, Christopher; Xue, Allen; Wasserman, Scott M; Hirayama, Atsushi

    2016-01-01

    Evolocumab (AMG 145), a fully human monoclonal antibody against PCSK9, significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in phase 2 and 3 studies. This phase 3 study evaluated the efficacy and safety of evolocumab plus atorvastatin in Japanese patients with hyperlipidemia or mixed dyslipidemia and high cardiovascular risk. Patients were randomized to atorvastatin 5 or 20 mg/day for 4 weeks. Subsequently, patients underwent second randomization to evolocumab 140 mg biweekly (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Coprimary end points were % change from baseline in LDL-C at week 12 and mean of weeks 10 and 12. Secondary end points included change and % change in other lipids and proportion of patients reaching LDL-C <70 mg/dl. Adverse events and laboratory values were recorded. Four hundred four patients were randomized to study drug. At baseline, the mean (SD) age was 61 (10) years (placebo) and 62 (11) years (evolocumab); 39% and 40% were women; 14% and 12% had cerebrovascular or peripheral arterial disease; and 51% and 47% had diabetes. At entry, mean (SD) calculated LDL-C was 128 (23) mg/dL; after stabilization on atorvastatin 5 and 20 mg/day, baseline LDL-C levels were 118 (35) and 94 (24) mg/dL, respectively. Mean LDL-C reductions at week 12 for evolocumab versus placebo ranged from 67% to 76%. No imbalances were observed in adverse events between treatment groups. Efficacy and safety for Q2W or QM evolocumab dosing were similar. In conclusion, in high-risk Japanese patients receiving stable statin therapy, evolocumab markedly reduced LDL-C and was well tolerated. PMID:26547291

  1. No contribution of the ABCB11 p.444A polymorphism in Japanese patients with drug-induced cholestasis.

    PubMed

    Kagawa, Tatehiro; Hirose, Shunji; Arase, Yoshitaka; Oka, Akira; Anzai, Kazuya; Tsuruya, Kota; Shiraishi, Koichi; Orii, Reiko; Ieda, Satsuki; Nakazawa, Takahide; Tomita, Kengo; Hokari, Ryota; Miura, Soichiro; Ebinuma, Hirotoshi; Saito, Hidetsugu; Kitamura, Tsuneo; Horie, Yoshinori; Okuse, Chiaki; Wasada, Mitsuru; Inoko, Hidetoshi; Tohkin, Masahiro; Saito, Yoshiro; Maekawa, Keiko; Takikawa, Hajime; Mine, Tetsuya

    2015-05-01

    European studies have revealed that the ABCB11 c.1331T>C (V444A) polymorphism (rs2287622) C-allele frequency is higher among patients with drug-induced cholestasis. Given the low incidence of this disease, however, this association has not been sufficiently elucidated. We aimed to investigate the significance of this polymorphism in Japanese patients. We determined ABCB11 V444A polymorphism frequencies and HLA genotypes in two independent drug-induced cholestasis cohorts. Expression and taurocholate transport activity of proteins from 444A variants were analyzed using Madin-Darby canine kidney II cells. In cohort 1 (n = 40), the V444A polymorphism C-allele frequency (66%) was lower than that in controls (n = 190, 78%), but this difference was not significant (P = 0.09). In cohort 2 (n = 119), comprising patients with cholestatic (n = 19), hepatocellular (n = 74), and mixed (n = 26) liver injuries, the C-allele frequency was lower among patients with cholestatic liver injury (68%) than among those with hepatocellular (75%) or mixed liver injury (83%), although this difference was not significant. In cohort 1, HLA-A*0201 was observed more frequently in patients (22%) than in controls [11%; P = 0.003; odds ratio, 2.4 (95% confidence interval, 1.4-4.0)]. Taurocholate transport activity of 444A-encoded protein was significantly lower than that of 444V-encoded protein (81% of 444V, P < 0.05) because of the reduced protein stability. In conclusion, ABCB11 444A had slightly reduced transport activity, but it did not contribute to the occurrence of drug-induced cholestasis in Japanese patients. Therefore, genetic susceptibility to acquired cholestasis may differ considerably by ethnicity. PMID:25713208

  2. Japanese encephalitis.

    PubMed

    Morita, K; Nabeshima, T; Buerano, C C

    2015-08-01

    Japanese encephalitis (JE) is an inflammation of the central nervous system in humans and animals, specifically horses and cattle. The disease, which can sometimes be fatal, is caused by the flavivirus Japanese encephalitis virus (JEV), of which there are five genotypes (genotypes 1, 2, 3, 4 and 5). The transmission cycle of the virus involves pigs and wild birds as virus amplifiers and mosquitoes as vectors for transferring the virus between amplifying hosts and to dead- end hosts, i.e. humans, horses and cattle. In horses and cattle the disease is usually asymptomatic, but when clinical signs do occur they include fever, decreased appetite, frothing at the mouth, rigidity of the legs and recumbency, and neurological signs, such as convulsive fits, circling, marked depression and disordered consciousness. In pigs, it can cause abortion and stillbirths. At present, the virus is detected in a wide area covering eastern and southern Asia, Indonesia, northern Australia, Papua New Guinea and Pakistan. JEV RNA has also been detected in Italy, first in dead birds in 1997 and 2000 and then in mosquitoes in 2010. Genotype shift, i.e. a change of genotype from genotype 3 to genotype 1, has occurred in some countries, namely Japan, South Korea, Chinese Taipei and Vietnam. Laboratory methods are available for confirming the causative agent of the disease. There are control measures to prevent or minimise infection and, among them, vaccination is one of the most important and one which should be adopted in endemic and epidemic areas. PMID:26601447

  3. Japanese encephalitis

    PubMed Central

    Yun, Sang-Im; Lee, Young-Min

    2014-01-01

    Japanese encephalitis (JE) is an infectious disease of the central nervous system caused by Japanese encephalitis virus (JEV), a zoonotic mosquito-borne flavivirus. JEV is prevalent in much of Asia and the Western Pacific, with over 4 billion people living at risk of infection. In the absence of antiviral intervention, vaccination is the only strategy to develop long-term sustainable protection against JEV infection. Over the past half-century, a mouse brain-derived inactivated vaccine has been used internationally for active immunization. To date, however, JEV is still a clinically important, emerging, and re-emerging human pathogen of global significance. In recent years, production of the mouse brain-derived vaccine has been discontinued, but 3 new cell culture-derived vaccines are available in various parts of the world. Here we review current aspects of JEV biology, summarize the 4 types of JEV vaccine, and discuss the potential of an infectious JEV cDNA technology for future vaccine development. PMID:24161909

  4. Things Japanese.

    ERIC Educational Resources Information Center

    Shigeta, Jessie M.

    Presented in this booklet are brief descriptions of items and activities that are symbolic of Japanese culture. Some of the items and activities described include Japanese musical instruments and records, toys and crafts, traditional clothing and accessories, and food utensils. Several recipes for Japanese dishes are provided. Lists of pertinent…

  5. Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study.

    PubMed

    Hirata, K; Takagi, H; Yamamoto, M; Matsumoto, T; Nishiya, T; Mori, K; Shimizu, S; Masumoto, H; Okutani, Y

    2008-02-01

    Genetic risk factors for ticlopidine-induced hepatotoxicity were determined in 22 Japanese patients with ticlopidine-induced hepatotoxicity and 85 Japanese patients who tolerated ticlopidine therapy without experiencing adverse reactions. There was a significant correlation between ticlopidine-induced hepatotoxicity and five human leukocyte antigen (HLA) alleles: HLA-A*3303, HLA-B*4403, HLA-Cw*1403, HLA-DRB1*1302 and HLA-DQB1*0604 (corrected probability (P)-value (Pc)<0.01). In particular HLA-A*3303 was present in 15 (68%) of the 22 patients with ticlopidine-induced hepatotoxicity and in 12 (14%) of the 85 ticlopidine-tolerant patients (odds ratio, 13.04; 95% confidence interval (CI), 4.40-38.59; the corrected P-value (Pc)=1.24 x 10(-5)). HLA-A*3303 was present in 12 (86%) of the 14 patients with ticlopidine-induced cholestatic hepatotoxicity (odds ratio, 36.50; 95% CI, 7.25-183.82, Pc=7.32 x 10(-7)). Ticlopidine-induced severe cholestatic hepatotoxicity occurred more frequently in subjects with HLA-A*3303 and its haplotype in Japanese patients. These findings may explain the high incidence of ticlopidine-induced hepatotoxicity in Japanese patients mediated via an immune-mediated mechanism. PMID:17339877

  6. Neuropsychological Impairment and Its Association with Violence Risk in Japanese Forensic Psychiatric Patients: A Case-Control Study

    PubMed Central

    Nishinaka, Hirofumi; Nakane, Jun; Nagata, Takako; Imai, Atsushi; Kuroki, Noriomi; Sakikawa, Noriko; Omori, Mayu; Kuroda, Osamu; Hirabayashi, Naotsugu; Igarashi, Yoshito; Hashimoto, Kenji

    2016-01-01

    Background In Japan, the legislation directing treatment of offenders with psychiatric disorders was enacted in 2005. Neuropsychological impairment is highly related to functional outcomes in patients with psychiatric disorders, and several studies have suggested an association between neuropsychological impairment and violent behaviors. However, there have been no studies of neuropsychological impairment in forensic patients covered by the Japanese legislation. This study is designed to examine the neuropsychological characteristics of forensic patients in comparison to healthy controls and to assess the relationship between neuropsychological impairment and violence risk. Methods Seventy-one forensic patients with psychiatric disorders and 54 healthy controls (matched by age, gender, and education) were enrolled. The CogState Battery (CSB) consisting of eight cognitive domains, the Iowa Gambling Task (IGT) to test emotion-based decision making, and psychological measures of violence risk including psychopathy were used. Results Forensic patients exhibited poorer performances on all CSB subtests and the IGT than controls. For each group, partial correlational analyses indicated that poor IGT performance was related to psychopathy, especially antisocial behavior. In forensic patients, the CSB composite score was associated with risk factors for future violent behavior, including stress and noncompliance with remediation attempts. Conclusion Forensic patients with psychiatric disorders exhibit a wide range of neuropsychological impairments, and these findings suggest that neuropsychological impairment may increase the risk of violent behavior. Therefore, the treatment of neuropsychological impairment in forensic patients with psychiatric disorders is necessary to improve functional outcomes as well as to prevent violence. PMID:26824701

  7. Targeted Exon Sequencing Successfully Discovers Rare Causative Genes and Clarifies the Molecular Epidemiology of Japanese Deafness Patients

    PubMed Central

    Kamatani, Naoyuki; Usami, Shin-ichi

    2013-01-01

    Target exon resequencing using Massively Parallel DNA Sequencing (MPS) is a new powerful strategy to discover causative genes in rare Mendelian disorders such as deafness. We attempted to identify genomic variations responsible for deafness by massive sequencing of the exons of 112 target candidate genes. By the analysis of 216randomly selected Japanese deafness patients (120 early-onset and 96 late-detected), who had already been evaluated for common genes/mutations by Invader assay and of which 48 had already been diagnosed, we efficiently identified causative mutations and/or mutation candidates in 57 genes. Approximately 86.6% (187/216) of the patients had at least one mutation. Of the 187 patients, in 69 the etiology of the hearing loss was completely explained. To determine which genes have the greatest impact on deafness etiology, the number of mutations was counted, showing that those in GJB2 were exceptionally higher, followed by mutations in SLC26A4, USH2A, GPR98, MYO15A, COL4A5 and CDH23. The present data suggested that targeted exon sequencing of selected genes using the MPS technology followed by the appropriate filtering algorithm will be able to identify rare responsible genes including new candidate genes for individual patients with deafness, and improve molecular diagnosis. In addition, using a large number of patients, the present study clarified the molecular epidemiology of deafness in Japanese. GJB2 is the most prevalent causative gene, and the major (commonly found) gene mutations cause 30–40% of deafness while the remainder of hearing loss is the result of various rare genes/mutations that have been difficult to diagnose by the conventional one-by-one approach. In conclusion, target exon resequencing using MPS technology is a suitable method to discover common and rare causative genes for a highly heterogeneous monogenic disease like hearing loss. PMID:23967202

  8. Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

    PubMed Central

    Tanaka, Yoshiya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Shoji, Toshiharu; Miyasaka, Nobuyuki; Koike, Takao

    2014-01-01

    Abstract Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate. Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules. Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules. PMID:24593170

  9. One-year effectiveness and safety of open-label losartan/hydrochlorothiazide combination therapy in Japanese patients with hypertension uncontrolled with ARBs or ACE inhibitors.

    PubMed

    Kita, Toshihiro; Yokota, Naoto; Ichiki, Yoshinari; Ayabe, Takao; Etoh, Takuma; Tamaki, Noboru; Kato, Johji; Eto, Tanenao; Kitamura, Kazuo

    2010-04-01

    The long-term antihypertensive efficacy and safety of losartan/hydrochlorothiazide (HCTZ) combinations have not been appropriately evaluated in Japan. In this study, treated hypertensive patients taking angiotensin-receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) regimens not at blood pressure (BP) goals proposed by the Japanese Society of Hypertension (JSH) were switched to losartan/HCTZ combinations and followed for 1 year. Data analysis included 244 patients aged 64.5+/-10.7 years, 56% male, 27% with diabetes mellitus and 36% with dyslipidemia. Pre-switching BP 157+/-16/88+/-10 mm Hg promptly decreased and maintained a steady state, reaching 132+/-15/77+/-9 mm Hg (P<0.001) 1 year later. After 1 year of treatment, 50% of patients cleared the goals of the JSH guideline for systolic BP and 79% for diastolic BP. Patients with maximal doses of ARBs tended to show larger decreases in BP (159+/-11/90+/-10 to 128+/-10/75+/-8 mm Hg, P<0.001, n=32). Clinical and laboratory adverse events were reported for 29 patients (11%), but serious abnormalities were not observed. In particular, plasma levels of uric acid (UA) were well-maintained for 1 year, and significant decreases in UA were observed in patients with higher levels of UA (>/=7.0 mg dl(-1)). Losartan/HCTZ combinations showed strong and steady hypotensive abilities and acceptable safety and tolerability in patients currently not at BP goals with regimens including ARBs or ACEIs in Japan. PMID:20075934

  10. Clinical characteristics of functional recovery after coronary artery bypass graft surgery in Japanese octogenarians

    PubMed Central

    Tobita, Ryo; Iwata, Kentaro; Kamisaka, Kenta; Yuguchi, Satoshi; Tahara, Masayuki; Oura, Keisuke; Morisawa, Tomoyuki; Ohhashi, Satoko; Kumamaru, Megumi; Hanafusa, Yusuke; Kato, Michitaka; Saitoh, Masakazu; Sakurada, Koji; Takahashi, Tetsuya

    2016-01-01

    [Purpose] This study aimed to elucidate characteristics of postoperative physical functional recovery in octogenarians undergoing coronary artery bypass graft surgery. [Subjects and Methods] This was a multi-center, retrospective study. Nine hundred and twenty-seven elective isolated coronary artery bypass graft surgeries were evaluated (746 males and 181 females, mean age: 68.6 years, range: 31–86 years). Participants were stratified according to age < 80 years (n = 840; mean age, 67.1; range, 31–79) or > 80 years (n = 87; mean age, 82.2; range, 80–86). Patient characteristics and postoperative physical functional recovery outcomes were compared between groups. [Results] There was no significant difference between groups when considering the postoperative day at which patients could sit on the edge of the bed, stand at bedside, or walk around the bed. The postoperative day at which patients could walk 100 m independently was later in octogenarians, when compared with non-octogenarians (6.1 ± 3.2 days vs. 4.9 ± 3.9 days). In octogenarians, the percentage of patients who could walk 100 m independently within 8 days after surgery was 79.5%. [Conclusion] A postoperative target time in octogenarians for independent walking, following coronary artery bypass grafting, can be set at approximately 6 days. PMID:27065553

  11. Japanese language and Japanese science

    NASA Astrophysics Data System (ADS)

    Tanikawa, Kiyotaka

    2003-08-01

    Japanese mathematical scientists including astronomers, physicists, and mathematicians obtain ideas in Japanese, discuss their problems in Japanese, and arrive at conclusions in Japanese, and yet they write their results in foreign languages such as English. This uncomfortable situation has continued for nearly one hundred years and has had serious effects on Japanese science. In this short report, the author discusses and analyses these effects. In order to put Japanese science on a sound basis, the author proposes to increase the number of articles, reviews and textbooks in Japanese, first by translation and second by the voluntary efforts of scientists themselves. As centers devoted to this activity, the author proposes to construct "Airborne Libraries" which are maintained and accumulate in an electronic form the scientific documents written in Japanese.

  12. A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets

    PubMed Central

    Kawahara, Tetsuya; Watanabe, Hiromi; Omae, Risa; Yamamoto, Toshiyuki; Inazu, Tetsuya

    2015-01-01

    X-linked hypophosphatemic rickets (XLH) is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. Inactivating mutations in the gene encoding phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) have been found to be associated with XLH. Here, we report a 16-year-old female patient affected by hypophosphatemic rickets. We evaluated her serum fibroblast growth factor 23 (FGF23) levels and conducted sequence analysis of the disease-associated genes of FGF23-related hypophosphatemic rickets: PHEX, FGF23, dentin matrix protein 1, and ectonucleotide pyrophosphatase/phosphodiesterase 1. She was diagnosed with XLH based on her clinical features and family history. Additionally, we observed elevated FGF23 levels and a novel PHEX exon 9 mutation (c.947G>T; p.Gly316Val) inherited from her father. Although bioinformatics showed that the mutation was neutral, Gly316 is perfectly conserved among humans, mice, and rats, and there were no mutations in other FGF23-related rickets genes, suggesting that in silico analysis is limited in determining mutation pathogenicity. In summary, we present a female patient and her father with XLH harboring a novel PHEX mutation that appears to be causative of disease. Measurement of FGF23 for hypophosphatemic patients is therefore useful for the diagnosis of FGF23-dependent hypophosphatemia. PMID:25861491

  13. Clinical pathology interpretation in geriatric veterinary patients.

    PubMed

    Metzger, Fred L; Rebar, Alan H

    2012-07-01

    Routine monitoring of clinicopathologic data is a critical component in the management of older patients because blood and urine testing allows the veterinarian to monitor trends in laboratory parameters, which may be the early indicators of disease. Laboratory profiling often provides an objective and sensitive indicator of developing disease before obvious clinical signs or physical examination abnormalities are observed. The primary key to the power of this evaluation is that the data are collected year after year during wellness checks and are examined serially. Chronic renal failure, chronic active hepatitis, canine hyperadrenocorticism, diabetes mellitus, and feline hyperthyroidism were reviewed and expected laboratory findings are summarized. PMID:22720804

  14. Type 1 Diabetes Mellitus and Pernicious Anemia in an Elderly Japanese Patient: A Case Report and Literature Review.

    PubMed

    Ohara, Nobumasa; Kaneko, Masanori; Yano, Toshio; Sato, Naoko; Usuda, Hiroyuki; Miyakoshi, Masashi; Furukawa, Tatsuo; Koike, Tadashi; Kaneko, Kenzo; Kamoi, Kyuzi

    2015-01-01

    We herein report the case of a 66-year-old Japanese man with acute-onset type 1 diabetes mellitus (T1D) accompanied by pernicious anemia. After 2 weeks of polyuria, the patient developed insulin-deficient hyperglycemia with diabetic ketoacidosis in the absence of verifiable islet-related autoantibodies and began insulin therapy in 2001. Eight years later, he developed gastric autoantibody-positive pernicious anemia and began methylcobalamin treatment. Previous studies have reported cases of slowly progressive autoimmune T1D concomitant with pernicious anemia. The present case suggests that potential associations with organ-specific autoimmune disorders should be considered during the long-term follow-up of T1D patients, even though verifiable islet-related autoantibodies are undetectable. PMID:26370862

  15. Phase I study of pegylated liposomal doxorubicin in combination with bortezomib for Japanese patients with relapsed or refractory multiple myeloma.

    PubMed

    Kusumoto, Shigeru; Sunami, Kazutaka; Inagaki, Mitsuo; Iida, Shinsuke

    2015-06-01

    This phase I open-label study evaluated the tolerability of pegylated liposomal doxorubicin (PLD) and bortezomib combination in Japanese patients with relapsed or refractory multiple myeloma. Eligible patients (≥20 years) who had ≥1 line of prior chemotherapy received bortezomib 1.3 mg/m(2) rapid intravenous infusion on days 1, 4, 8 and 11 (each 21-day cycle), followed by PLD 30 mg/m(2) intravenous infusion on day 4 (each cycle), up to 6 cycles. Dose-limiting toxicity (DLT), defined as Grade 4 hematologic or Grade ≥3 non-hematologic, was evaluated through end of day 21. All three patients enrolled in the study developed DLTs [Grade 4 thrombocytopenia (n = 2) and Grade 3 ileus (n = 1)]. The study was, therefore, terminated without adding new patients, as per protocol-specified criteria. The most common Grade 3-4 adverse events (AEs) were hematologic, including thrombocytopenia, leucopenia, and neutropenia. The treatment was prematurely discontinued in all three patients due to AEs: Grade 3 bronchiolitis (serious AE), Grade 3 peripheral sensory neuropathy, and Grade 2 stomatitis. All patients achieved partial response (efficacy, secondary endpoint). In conclusion, the tolerability of PLD and bortezomib combination at dose levels approved in various countries was not confirmed in relapsed or refractory multiple myeloma patients from Japan. PMID:25749662

  16. Appropriate Tongue Blade Length of the Dingman Mouth Gag for Japanese Pediatric Patients With Cleft Palate and Mandibular Micrognathia.

    PubMed

    Satoh, Koji; Aizawa, Takako; Kobayashi, Yoshikazu; Mizutani, Hideki; Yamada, Morimasa

    2016-03-01

    Objective Our objective is to determine appropriate specifications for smaller tongue blade for Japanese pediatric patients with cleft palate (CP) and mandibular micrognathia. Patients We investigated 59 patients who underwent palatoplasty. Patients were divided into two groups: the micrognathia (MG) group consisted of 11 patients and the normognathia (NG) group consisted of 48 patients. Interventions The following five items were investigated retrospectively: (1) gender, (2) cleft type, (3) age at the time of surgery, (4) weight at the time of surgery, and (5) distance from the tongue blade base to the posterior pharyngeal wall (Dis). Results There was a significant difference (P < .01) in age at the time of surgery and in Dis between groups, but not in weight. The minimum values were 55 mm for the MG group. As for correlations between age and weight at the time of surgery, the P values for the MG and NG groups were .993 and .052, respectively. As for correlations between weight at the time of surgery and Dis, the P values for the MG and NG groups were .987 and .099, respectively. Conclusions It was difficult to predict Dis on the basis of the patient's age and weight measured preoperatively. The minimum Dis was 55 mm, equal to the length from the base to the tip of the Dingman Mouth Gag tongue blade currently in use, suggesting that a tongue blade of approximately 50 mm in length, shorter than the current minimum specifications, may be appropriate. PMID:25607241

  17. Larva migrans syndrome caused by Toxocara and Ascaris roundworm infections in Japanese patients.

    PubMed

    Yoshida, A; Hombu, A; Wang, Z; Maruyama, H

    2016-09-01

    Larva migrans syndrome (LMS) caused by Toxocara and Ascaris roundworms is generally believed to be more common in children, while a report from Japan suggests that it is more common in adults. We conducted a large-scale retrospective study to confirm these findings and to clarify what caused the difference between Japan and other countries, to reveal overlooked aspects of this disease. The clinical information of 911 cases which we diagnosed as Toxocara or Ascaris LMS during 2001 and 2015 was analysed. Information used included age, sex, address (city or county), chief complaint, present history, dietary history, overseas travelling history, medical imaging findings and laboratory data (white blood cell count, peripheral blood eosinophil number and total IgE). The sex ratio of the disease was 2.37 (male/female = 641/270). The number of patients not younger than 20 years old were 97.8 and 95.1 % among males and females, respectively. Major disease types were visceral, ocular, neural and asymptomatic. The visceral type was more prevalent in older patients, while younger patients were more vulnerable to ocular symptoms. More than two-thirds of the patients whose dietary habits were recorded had a history of ingesting raw or undercooked animal meat. LMS caused by Toxocara or Ascaris is primarily a disease of adult males in Japan, who probably acquired infections by eating raw or undercooked animal meat/liver. Healthcare specialists should draw public attention to the risk of raw or undercooked animal meat in Europe as well. PMID:27272122

  18. Primary Gleason Grade 4 Impact on Biochemical Recurrence After Permanent Interstitial Brachytherapy in Japanese Patients With Low- or Intermediate-Risk Prostate Cancer

    SciTech Connect

    Uesugi, Tatsuya; Saika, Takashi; Edamura, Kohei; Nose, Hiroyuki; Kobuke, Makoto; Ebara, Shin; Abarzua, Fernand; Katayama, Norihisa; Yanai, Hiroyuki; Nasu, Yasutomo; Kumon, Hiromi

    2012-02-01

    Purpose: To reveal a predictive factor for biochemical recurrence (BCR) after permanent prostate brachytherapy (PPB) using iodine-125 seed implantation in patients with localized prostate cancer classified as low or intermediate risk based on National Comprehensive Cancer Network (NCCN) guidelines. Methods and Materials: From January 2004 to December 2009, 414 consecutive Japanese patients with clinically localized prostate cancer classified as low or intermediate risk based on the NCCN guidelines were treated with PPB. The clinical factors including pathological data reviewed by a central pathologist and follow-up data were prospectively collected. Kaplan-Meier and Cox regression analyses were used to assess the factors associated with BCR. Results: Median follow-up was 36.5 months. The 2-, 3-, 4-, and 5-year BCR-free rates using the Phoenix definition were 98.3%, 96.0%, 91.6%, and 87.0%, respectively. On univariate analysis, the Gleason score, especially primary Gleason grade 4 in biopsy specimens, was a strong predicting factor (p < 0.0001), while age, initial prostate-specific antigen (PSA) level, T stage, and minimal dose delivered to 90% of the prostate volume (D90) were insignificant. Multivariate analysis indicated that a primary Gleason grade 4 was the most powerful prognostic factor associated with BCR (hazard ratio = 6.576, 95% confidence interval, 2.597-16.468, p < 0.0001). Conclusions: A primary Gleason grade 4 carried a worse BCR prognosis than the primary grade 3 in patients treated with PPB. Therefore, the indication for PPB in patients with a Gleason sum of 4 + 3 deserves careful and thoughtful consideration.

  19. Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F

    SciTech Connect

    Yagi, T.; Tatsumi-Miyajima, J.; Sato, M.; Kraemer, K.H.; Takebe, H. )

    1991-06-15

    To assess the contribution to mutagenesis by human DNA repair defects, a UV-treated shuttle vector plasmid, pZ189, was passed through fibroblasts derived from Japanese xeroderma pigmentosum (XP) patients in two different DNA repair complementation groups (A and F). Patients with XP have clinical and cellular UV hypersensitivity, increased frequency of skin cancer, and defects in DNA repair. The XP DNA repair defects represented by complementation groups A (XP-A) and F (XP-F) are more common in Japan than in Europe or the United States. In comparison to results with DNA repair-proficient human cells (W138-VA13), UV-treated pZ189 passed through the XP-A (XP2OS(SV)) or XP-F (XP2YO(SV)) cells showed fewer surviving plasmids (XP-A less than XP-F) and a higher frequency of mutated plasmids (XP-A greater than XP-F). Base sequence analysis of more than 200 mutated plasmids showed the major type of base substitution mutation to be the G:C----A:T transition with all three cell lines. The XP-A and XP-F cells revealed a higher frequency of G:C----A:T transitions and a lower frequency of transversions among plasmids with single or tandem mutations and a lower frequency of plasmids with multiple point mutations compared to the normal line. The spectrum of mutations in pZ189 with the XP-A cells was similar to that with the XP-F cells. Seventy-six to 91% of the single base substitution mutations occurred at G:C base pairs in which the 5{prime}-neighboring base of the cytosine was thymine or cytosine. These studies indicate that the DNA repair defects in Japanese XP patients in complementation groups A and F result in different frequencies of plasmid survival and mutagenesis but in similar types of mutagenic abnormalities despite marked differences in clinical features.

  20. Comparison of Azelnidipine and Trichlormethiazide in Japanese Type 2 Diabetic Patients with Hypertension: The COAT Randomized Controlled Trial

    PubMed Central

    Takihata, Masahiro; Nakamura, Akinobu; Kondo, Yoshinobu; Kawasaki, Satsuki; Kimura, Mari; Terauchi, Yasuo

    2015-01-01

    Objective This study compared the efficacy and safety of azelnidipine with that of trichlormethiazide in Japanese type 2 diabetic patients with hypertension. Methods In a multicenter, open-label trial, 240 patients with adequately controlled diabetes (HbA1c ≤ 7.0%) under lifestyle modification and/or administration of hypoglycemic agents and inadequately controlled hypertension (systolic blood pressure [sBP] ≥ 130 mmHg or diastolic blood pressure [dBP] ≥ 80 mmHg) who were being treated with olmesartan were enrolled. Participants were randomly assigned to an azelnidipine group or a trichlormethiazide group and were followed up for 48 weeks. Main outcome measure was the difference in the change in HbA1c levels from the baseline values at 48 weeks between these two groups. Results Of the 240 subjects that were enrolled, 209 subjects (azelnidipine group: 103 patients, trichlormethiazide group: 106 patients) completed this trial. At 48 weeks, the following changes were observed in the azelnidipine and trichlormethiazide groups, respectively: HbA1c levels, 0.19 ± 0.52% and 0.19 ± 0.54%; sBP/dBP, -10.7 ± 9.6/-6.6 ± 6.6 mmHg and -7.1 ± 7.7/-3.3 ± 6.1 mmHg (P < 0.001 for both sBP and dBP). In both groups, dizziness (12 patients [11.7%] and 16 patients [15.1%]) and edema (16 patients [15.5%] and 7 patients [6.6%], P = 0.047) were observed during the 48-week follow-up period. Conclusions Azelnidipine was more effective for controlling blood pressure than trichlormethiazide in Japanese type 2 diabetes patients, whereas trichlormethiazide was more effective for reducing albuminuria than azelnidipine. Both of these agents, however, similarly exacerbated glycemic control in type 2 diabetic patients with hypertension. Trial Registration UMIN 000006081. PMID:25938807

  1. Benefits of use, and tolerance of, medium-chain triglyceride medical food in the management of Japanese patients with Alzheimer’s disease: a prospective, open-label pilot study

    PubMed Central

    Ohnuma, Tohru; Toda, Aiko; Kimoto, Ayako; Takebayashi, Yuto; Higashiyama, Ryoko; Tagata, Yuko; Ito, Masanobu; Ota, Tsuneyoshi; Shibata, Nobuto; Arai, Heii

    2016-01-01

    Objectives This is the first clinical trial of this type in Japan, designed to analyze two important aspects of Alzheimer’s disease (AD) management using medium-chain triglycerides. Axona was administered for 3 months (40 g of powder containing 20 g of caprylic triglycerides). We used an indurating, four-step dose-titration method (from 10 to 40 g per day) for 7 days before the trial, and examined the tolerance and adverse effects of this intervention. We also investigated its effect on cognitive function in mild-to-moderate AD patients. Patients and methods This was a clinical intervention in 22 Japanese patients with sporadic AD at a mild-to-moderate stage (ten females, 12 males), mean age (± standard deviation) 63.9 (±8.5) years, Mini-Mental State Examination (MMSE) score, 10–25, seven patients were ApoE4-positive. During Axona administration, we examined changes in cognitive function by obtaining MMSE and AD assessment-scale scores. Intolerance and serum ketone concentrations were also examined. Results The tolerance of Axona was good, without severe gastrointestinal adverse effects. Axona did not improve cognitive function in our sample of AD patients, even in those patients without the ApoE4 allele. However, some ApoE4-negative patients with baseline MMSE score ≥14 showed improvement in their cognitive functions. Conclusion The modified dose-titration method, starting with a low dose of Axona, decreased gastrointestinal adverse effects in Japanese patients. Axona might be effective for some relatively mildly affected patients with AD (with cognitive function MMSE score of ≥14 and lacking the ApoE4 allele). PMID:26811674

  2. Safety of Adalimumab and Predictors of Adverse Events in 1693 Japanese Patients with Crohn’s Disease

    PubMed Central

    Watanabe, Mamoru; Matsui, Toshiyuki; Hase, Hidenori; Okayasu, Motohiro; Tsuchiya, Tsuyoshi; Shinmura, Yasuhiko; Hibi, Toshifumi

    2016-01-01

    Background and Aims: Data from an all-cases post-marketing study were used to evaluate the safety and effectiveness of adalimumab in Japanese patients with Crohn’s disease [CD]. Methods: Patients received adalimumab for 24 weeks. Data from all patients [n = 1693] were used for the safety assessment. Data from patients with CD activity index [CDAI] ≥ 150 at baseline were used for the effectiveness assessment. Results: The most frequent serious adverse drug reaction [ADR] was infection and infestations [6.6 events/100 patient-years]. The risk of serious infections increased in patients who had a history of malignancy and those with concomitant corticosteroid use. Of 415 patients who had switched from another anti-tumour necrosis factor alpha [TNFα] agent to adalimumab due to ADRs, 7.2% discontinued due to ADRs to adalimumab. Ten of 13 patients with a history of tuberculosis [TB] received prophylactic medication, and none developed TB. TB developed in one patient with no history of TB or anti-TB prophylaxis. Remission rates were 41.3% and 32.4% at 4 and 24 weeks, respectively. Remission rates did not differ between patients with and without concomitant use of immunomodulators. Predictive variables for increased effectiveness were CDAI ≤ 220 and disease duration of ≤ 2 years. Perianal lesions and loss of response to previous anti-TNFα agents affected effectiveness. Conclusions: The most frequent serious ADR was infection. Adalimumab significantly reduced disease activity, without any unexpected ADRs. Development of active TB during adalimumab therapy can be prevented through TB screening and prophylaxis. In patients who switched from another anti-TNFα agent to adalimumab due to ADRs, adalimumab was well tolerated. PMID:26961546

  3. A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome.

    PubMed

    Christianto, Antonius; Katayama, Syouichi; Kameshita, Isamu; Inazu, Tetsuya

    2016-08-01

    Rett syndrome (RTT) is a severe X-linked dominant inheritance disorder with a wide spectrum of clinical manifestations. Mutations in Methyl CpG binding protein 2 (MECP2), Cyclin dependent kinase-like 5 (CDKL5) and Forkhead box G1 (FOXG1) have been associated with classic and/or variant RTT. This study was conducted to identify the responsible gene(s) in atypical RTT patient, and to examine the effect of the mutation on protein function. DNA sequence analysis showed a novel heterozygous mutation in CDKL5 identified as c.530A>G which resulted in an amino acid substitution at position 177, from tyrosine to cysteine. Genotyping analysis indicated that the mutation was not merely a single nucleotide polymorphism (SNP). We also revealed that patient's blood lymphocytes had random X-chromosome inactivation (XCI) pattern. Further examination by bioinformatics analysis demonstrated the mutation caused damage or deleterious in its protein. In addition, we demonstrated in vitro kinase assay of mutant protein showed impairment of its activity. Taken together, the results suggested the mutant CDKL5 was responsible for the disease. PMID:27265524

  4. Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia.

    PubMed

    Higashiyama, Ryoko; Ohnuma, Tohru; Takebayashi, Yuto; Hanzawa, Ryo; Shibata, Nobuto; Yamamori, Hidenaga; Yasuda, Yuka; Kushima, Itaru; Aleksic, Branko; Kondo, Kenji; Ikeda, Masashi; Hashimoto, Ryota; Iwata, Nakao; Ozaki, Norio; Arai, Heii

    2016-04-01

    Chromosome 22q11.2 deletion syndrome and genetic variations including single-nucleotide polymorphism (SNP) and copy number variation (CNV) in catechol-O-methyltransferase (COMT) situated at 22q11.2 remains controversial. Here, the genetic relationship between COMT and Japanese patients with schizophrenia was investigated by examining whether the SNPs correlated with schizophrenia based on a common disease-common variant hypothesis. Additionally, 22q11.2DS were screened based on a common disease-rare variant hypothesis; low-frequency CNVs situated at two COMT promoters and exons were investigated based on the low-frequency variants with an intermediate effect; and positive findings from the first stage were reconfirmed using a second-stage replication study including a larger sample size. Eight SNPs and 10 CNVs were investigated using Taqman SNP and CNV quantitative real-time polymerase chain reaction method. For the first-stage analysis, 513 unrelated Japanese patients with schizophrenia and 705 healthy controls were examined. For the second-stage replication study, positive findings from the first stage were further investigated using a larger sample size, namely 1,854 patients with schizophrenia and 2,137 controls. The first-stage analysis showed significant associations among schizophrenia, intronic SNP rs165774, CNV6 situated at promoter 1, CNV8 at exon 6, and CNV9 at exon 7. The second-stage study showed that intronic SNP rs165774 (χ(2)  = 8.327, P = 0.0039), CNV6 (χ(2)  = 19.66, P = 0.00005), and CNV8 (χ(2)  = 16.57, P = 0.00025) were significantly associated with schizophrenia. Large and rare CNVs as well as low-frequency CNVs and relatively small CNVs, namely <30 kb in COMT, may be genetic risk factors for schizophrenia. © 2016 Wiley Periodicals, Inc. PMID:26852906

  5. Effects of valsartan and amlodipine on cardiorenal protection in Japanese hypertensive patients: the Valsartan Amlodipine Randomized Trial.

    PubMed

    Narumi, Hiroya; Takano, Hiroyuki; Shindo, Satoshi; Fujita, Miwa; Mizuma, Hiroshi; Kuwabara, Yoichi; Komuro, Issei

    2011-01-01

    The Valsartan Amlodipine Randomized Trial, a multicenter, prospective, randomized, open-labeled, blinded-end point trial, was designed to compare the beneficial effects of the angiotensin II receptor blocker valsartan and the calcium channel blocker amlodipine on cardiovascular events in Japanese essential hypertensive patients. The primary end point was a composite of all-cause death, sudden death, cerebrovascular death, cardiac events, vascular events and renal events. The secondary endpoints were effects on left ventricular hypertrophy, cardiac sympathetic nerve activity and renal function. A total of 1021 patients were enrolled in the present trial. The mean follow-up period was 3.4 years. There were no significant differences in blood pressure (BP) levels between the valsartan group and the amlodipine group throughout the trial. There was no significant difference in the primary endpoint between the two groups (hazard ratio: 1.0, P = 0.843). No difference in any event category of the primary endpoint was noted for either group. However, we observed a significant reduction of left ventricular mass index, as determined by echocardiography, in the valsartan group compared with the amlodipine group. We also observed a significant decrease in cardiac sympathetic nerve activity in the valsartan group but not in the amlodipine group. Moreover, there was a significant reduction in the urinary albumin to creatinine ratio in the valsartan group but not in the amlodipine group. Therefore, although BP levels were well controlled and remained equal in the two groups, valsartan had more protective effects on the heart and kidney than amlodipine in Japanese hypertensive patients. PMID:20927112

  6. [Safety and Tolerance of Dose-Dense Epirubicin and Cyclophosphamide (EC) with Pegfilgrastim for Japanese Patients with Early Breast Cancer].

    PubMed

    Watanabe, Kenichi; Sato, Masako; Yamamoto, Mitsugu; Ikarashi, Mayuko; Hagio, Kanako; Tomioka, Nobumoto; Tamaki, Shinya; Takahashi, Yumi; Takahasi, Masato

    2016-04-01

    With the approval of pegfilgrastim, the use of dose-dense epirubicin and cyclophosphamide (EC) for breast cancer has become acceptable in Japan. Thus, we aimed to evaluate its safety and tolerability in Japanese patients. Nine breast cancer patients with a high risk of preoperative or postoperative recurrence received EC therapy(epirubicin 90 mg/m(2) and cyclo- phosphamide 600 mg/m(2))for 4 cycles every 2 weeks in combination with a subcutaneous injection of pegfilgrastim (3.6 mg) on day 2 of each cycle. Treatment was discontinued in 1 and extended in 1 of the 9 patients, and the mean relative dose intensity(RDI)was good at 0.93. No serious adverse events were observed, indicating good tolerability. The regimen has potential for use in cases in which the treatment dose needs to be increased. grade 4 neutropenia was observed in all the 9 patients on day 8, with 6 patients developing febrile neutropenia. In Japan, data on changes in neutrophil count associated with pegfilgrastim administration under anthracycline-based chemotherapy are currently insufficient, and further study is required. PMID:27220788

  7. Impact of Body Mass Index on the Prognosis of Japanese Patients With Non-Valvular Atrial Fibrillation.

    PubMed

    Inoue, Hiroshi; Kodani, Eitaro; Atarashi, Hirotsugu; Okumura, Ken; Yamashita, Takeshi; Origasa, Hideki

    2016-07-15

    Obesity is a risk factor for atrial fibrillation (AF); however, obesity is associated with lower mortality in patients with established AF, a phenomenon known as the obesity paradox. Previous studies reported inconsistent results regarding effects of body weight on risk of cardiogenic embolism in patients with AF. To determine relation between body mass index (BMI) and prognosis among Japanese patients with nonvalvular AF (NVAF), a post hoc analysis was conducted using observational data in the J-RHYTHM Registry. Subjects were categorized as underweight (BMI <18.5), normal (18.5 to 24.9), overweight (25.0 to 29.9), or obese (≥30 kg/m(2)). End points included thromboembolism, major hemorrhaging, all-cause mortality, and cardiovascular mortality. Of the 7,406 patients with NVAF, 6,379 patients (70 ± 10 years old; BMI, 23.6 ± 3.9 kg/m(2)) having baseline BMI data constituted the study group. During the 2-year follow-up period, 111 patients had thromboembolism, 124 experienced major hemorrhage, and 159 died. Multivariate analysis with the Cox proportional hazards model showed that none of the BMI categories were independent predictors of thromboembolism. However, being underweight was an independent predictor of all-cause mortality (hazard ratio [HR] 2.45; 95% confidence interval [CI] 1.62 to 3.69; p <0.001) and cardiovascular mortality (HR 3.00, 95% CI 1.52 to 5.91, p = 0.001) when normal weight was used as the reference. Additionally, being overweight was a predictor of lower all-cause mortality (HR 0.60, 95% CI 0.37 to 0.95, p = 0.029). In conclusion, being underweight is associated with higher risks of all-cause and cardiovascular mortality compared with having a normal weight. Being overweight or obese is not associated with increased mortality among Japanese patients with NVAF. PMID:27255662

  8. The Different Association between Serum Ferritin and Mortality in Hemodialysis and Peritoneal Dialysis Patients Using Japanese Nationwide Dialysis Registry

    PubMed Central

    Maruyama, Yukio; Yokoyama, Keitaro; Yokoo, Takashi; Shigematsu, Takashi; Iseki, Kunitoshi; Tsubakihara, Yoshiharu

    2015-01-01

    Background/Aims Monitoring of serum ferritin levels is widely recommended in the management of anemia among patients on dialysis. However, associations between serum ferritin and mortality are unclear and there have been no investigations among patients undergoing peritoneal dialysis (PD). Methods Baseline data of 191,902 patients on dialysis (age, 65 ± 13 years; male, 61.1%; median dialysis duration, 62 months) were extracted from a nationwide dialysis registry in Japan at the end of 2007. Outcomes, such as one-year mortality, were then evaluated using the registry at the end of 2008. Results Within one year, a total of 15,284 (8.0%) patients had died, including 6,210 (3.2%) cardiovascular and 2,707 (1.4%) infection-related causes. Higher baseline serum ferritin levels were associated with higher mortality rates among patients undergoing hemodialysis (HD). In contrast, there were no clear associations between serum ferritin levels and mortality among PD patients. Multivariate Cox regression analysis of HD patients showed that those in the highest serum ferritin decile group had higher rates of all-cause and cardiovascular mortality than those in the lowest decile group (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.31–1.81 and HR, 1.44; 95% CI, 1.13–1.84, respectively), whereas associations with infection-related mortality became non-significant (HR, 1.14; 95% CI, 0.79–1.65). Conclusions Using Japanese nationwide dialysis registry, higher serum ferritin values were associated with mortality not in PD patients but in HD patients. PMID:26599216

  9. Clinical nurses' characterizations of patient coping problems.

    PubMed

    Becket, N

    1991-01-01

    The author reports the findings from a qualitative study of diagnostic data obtained and interpreted by hospital nurses on the coping of adult patients and their families. Clinical data taken from taped interviews were transcribed and analyzed using grounded theory and analytic induction techniques. The data were then compared with diagnoses accepted for testing by NANDA. The phenomena described by the research did not match the NANDA constructs for individual and family coping problems. Nurses' assessments of coping response, however, fit within transactional theory. The use of the term "ineffective" to qualify coping was generally avoided. Ineffective coping, suggesting an outcome or product of coping, was not often considered applicable to the coping responses nurses found appropriate at specific times in specific situations. PMID:1873103

  10. [Documented nursing diagnoses for medical clinic patients].

    PubMed

    Fontes, Cassiana Mendes Bertoncello; da Cruz, Diná Almeida Lopes Monteiro

    2007-09-01

    This paper reports a descriptive study, based on nursing records, of nursing diagnoses documented three months after the implementation of the NANDA-I classification at the University of São Paulo's Hospital Universitário (HU-USP) and proposes outcomes and interventions for the 3 most frequent diagnoses. The convenience sample (34% of the month's admissions) consisted of 30 charts of patients admitted in the Medical Clinic in August of 2004 (60% female, average age 60.9 +/- 23.1 years, mean length of stay = 5.8 +/- 2.7 days). The diagnoses documented on the admission day were manually transcribed from the charts and analyzed according to their frequency. There were 144 diagnoses (31 categories), with an average of 4.8 +/- 4.0 diagnoses per patient (range = 1-10). The most frequent were: acute pain (66.7%), impaired tissue integrity (63.3%), ineffective airway clearance (43.3%), risk of impaired skin integrity (36.7%), and impaired skin integrity (33.3%). The proposed outcomes and interventions are presented. PMID:17977375