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Sapporo, Japan

Mizuta S.,Fujita Health University Hospital | Matsuo K.,Kyushu University | Nishiwaki S.,Nagoya University | Imai K.,Sapporo Hokuyu Hospital | And 13 more authors.
Blood | Year: 2014

We aimed to evaluate the impact of pretransplant imatinib administration on the outcome of allogeneic hematopoietic stem cell transplantation(allo-HSCT) in adults with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We retrospectively analyzed 738 patients with Ph+ ALL that underwent allo-HSCT between 1990 and 2010 using data from the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation. We compared the allo-HSCT outcomes between 542 patients who received imatinib before allo-HSCT during the initial complete remission period (imatinib cohort) and 196 patients who did not receive imatinib (non-imatinib cohort). The 5-year overall survival after allo-HSCT was significantly higher in the imatinib cohort than in the non-imatinib cohort (59% vs 38%; 95% confidence interval [CI], 31-45%; P < .001). Multivariate analysis indicated that pretransplant imatinib administration had beneficial effects on overall survival (hazardratio [HR], 0.57; 95%CI, 0.42-0.77; P < .001), relapse (HR, 0.66; 95% CI, 0.43-0.99; P = .048), and nonrelapse mortality (HR, 0.55; 95% CI, 0.37-0.83; P = .005). In conclusion, our study showed that imatinib administration before allo-HSCT had advantageous effects on the clinical outcomes of allo-HSCT in patients with Ph+ ALL. © 2014 by The American Society of Hematology. Source

Hyponatremia is the most common electrolyte abnormality in hospitalized patients. The objective of this study was to identify risk factors for hyponatremia during chemotherapy in children. A total of 111 consecutive pediatric patients (age, 0 to 18 y) with hematological malignancy (n=87) or solid tumor (n=24) who received chemotherapy in our hospital between 2010 and 2014 were enrolled. The number of chemotherapy cycles reviewed was 472, with a median of 3 (range, 1 to 8) per patient. Hyponatremia was defined as a serum sodium level of <135 mmol/L. Hyponatremia was observed in 80 of 111 (72%) patients, and 138 of 472 (29%) cycles. Neurological sequelae were seen in 2 of 111 (2%) patients, and 2 of 472 (0.4%) cycles. Multivariate logistic regression identified age 10 to 18 years (odds ratio [OR]=3.24, 95% confidence interval [CI], 2.07-5.07), total parenteral nutrition (OR=8.15, 95% CI, 2.17-30.5), first or second chemotherapy cycle (OR=1.74, 95% CI, 1.12-2.70) as independent risk factors for hyponatremia. Clinical conditions of patients and chemotherapeutic agents may have a profound impact on the development of hyponatremia. Patients with these factors should be managed carefully to prevent severe symptoms and sequelae caused by hyponatremia. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

Kaneko K.,Tohoku University | Furuyama K.,Tohoku University | Furuyama K.,Iwate University | Fujiwara T.,Tohoku University | And 4 more authors.
Haematologica | Year: 2014

Erythroid-specific 5-aminolevulinate synthase (ALAS2) is the rate-limiting enzyme for heme biosynthesis in erythroid cells, and a missense mutation of the ALAS2 gene is associated with congenital sideroblastic anemia. However, the gene responsible for this form of anemia remains unclear in about 40% of patients. Here, we identify a novel erythroid-specific enhancer of 130 base pairs in the first intron of the ALAS2 gene. The newly identified enhancer contains a cis-acting element that is bound by the erythroid-specific transcription factor GATA1, as confirmed by chromatin immunoprecipitation analysis in vivo and by electrophoretic mobility shift assay in vitro. A promoter activity assay in K562 human erythroleukemia cells revealed that the presence of this 130-base pair region increased the promoter activity of the ALAS2 gene by 10-15-fold. Importantly, two mutations, each of which disrupts the GATA-binding site in the enhancer, were identified in unrelated male patients with congenital sideroblastic anemia, and the lower expression level of ALAS2 mRNA in bone marrow erythroblasts was confirmed in one of these patients. Moreover, GATA1 failed to bind to each mutant sequence at the GATA-binding site, and each mutation abolished the enhancer function on ALAS2 promoter activity in K562 cells. Thus, a mutation at the GATA-binding site in this enhancer may cause congenital sideroblastic anemia. These results suggest that the newly identified intronic enhancer is essential for the expression of the ALAS2 gene in erythroid cells. We propose that the 130-base pair enhancer region located in the first intron of the ALAS2 gene should be examined in patients with congenital sideroblastic anemia in whom the gene responsible is unknown. © 2013 Ferrata Storti Foundation. Source

Kukita K.,Sapporo Hokuyu Hospital
Journal of Vascular Access | Year: 2015

Introduction: The Japanese Society for Dialysis Access (JSDA) has held the practical skills trainings for the doctors working for the vascular access (VA) access since 2014 in order to improve both quality and quantity of the VA construction. Terumo Medical Pranex (Kanagawa, Japan) is the institution of the general medical training established for the creation and the spread of medical technique, and it also has the hybrid simulator of VA. Methods and results: In the training institute in 2014, not only the practical skills but also the training on the simulator from the basic lecture of VA construction were conducted. The dummy of a radical artery and a cephalic vein is faked in the forearm on the simulator. Two carotid arteries of a pig are made as the position of a pair of artery and vein. The pig’s skin taken from the neck to the chest is covered on the proceed part, then the dummy forearm was completed. We can make recognize the beats in the artery. We also can make a fake avf in the dummy forearm instead. The instructor is directly able to give the trainees the lectures while watching the scenes. jsda will continue to make such efforts from now. Conclusions: We are concerned that the more the VA access would be demanded, the more the VA construction would be needed. So, the matter of the urgency is the training of the doctors working for VA construction. © 2015 Wichtig Publishing. Source

Mori M.,Yokohama City University | Kobayashi R.,Sapporo Hokuyu Hospital | Kato K.,Red Cross | Maeda N.,National Hospital Organization Nagoya Medical Center | And 7 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2015

The aim of this study was to investigate the pharmacokinetics, safety, and tolerability of voriconazole following intravenous-tooral 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.) Copyright © 2015 American Society for Microbiology. All Rights Reserved. Source

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