Tsurugashima, Japan
Tsurugashima, Japan

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Hirama T.,Saitama University | Yamaguchi T.,Saitama University | Miyazawa H.,Saitama University | Tanaka T.,Saitama University | And 16 more authors.
PLoS ONE | Year: 2011

Commensal organisms are frequent causes of pneumonia. However, the detection of these organisms in the airway does not mean that they are the causative pathogens; they may exist merely as colonizers. In up to 50% cases of pneumonia, the causative pathogens remain unidentified, thereby hampering targeting therapies. In speculating on the role of a commensal organism in pneumonia, we devised the battlefield hypothesis. In the "pneumonia battlefield," the organism-to-human cell number ratio may be an index for the pathogenic role of the organism. Using real-time PCR reactions for sputum samples, we tested whether the hypothesis predicts the results of bacteriological clinical tests for 4 representative commensal organisms: Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas spp., and Moraxella catarrhalis. The cutoff value for the organism-to-human cell number ratio, above which the pathogenic role of the organism was suspected, was set up for each organism using 224 sputum samples. The validity of the cutoff value was then tested in a prospective study that included 153 samples; the samples were classified into 3 groups, and each group contained 93%, 7%, and 0% of the samples from pneumonia, in which the pathogenic role of Streptococcus pneumoniae was suggested by the clinical tests. The results for Haemophilus influenzae, Pseudomonas spp., and Moraxella catarrhalis were 100%, 0%, and 0%, respectively. The battlefield hypothesis enabled legitimate interpretation of the PCR results and predicted pneumonia in which the pathogenic role of the organism was suggested by the clinical test. The PCR reactions based on the battlefield hypothesis may help to promote targeted therapies for pneumonia. The prospective observatory study described in the current report had been registered to the University Hospital Medical Information Network (UMIN) registry before its initiation, where the UMIN is a registry approved by the International Committee of Medical Journal Editors (ICMJE). The UMIN registry number was UMIN000001118: A prospective study for the investigation of the validity of cutoff values established for the HIRA-TAN system (April 9, 2008). © 2011 Hirama et al.


Hirama T.,Saitama University | Minezaki S.,Saitama University | Yamaguchi T.,Saitama University | Kishi E.,Saitama University | And 10 more authors.
Respiratory Medicine | Year: 2014

Identification of the causative pathogen(s) of pneumonia would allow the selection of effective antibiotics and thus reduce the mortality rate and the emergence of drug-resistant pathogens. To identify such pathogens and to obtain these benefits, it is necessary that a clinical test is rapid, accurate, easily performed, and cost-effective. Here, we devised a PCR-based test, named HIRA-TAN, which is able to discriminate therapeutic targets from commensal organisms (e.g. Streptococcus pneumoniae or Haemophilus influenzae) and to detect foreign organisms (e.g. Mycoplasma pneumoniae or Legionella pneumophila) in the sputum. The utility of this system was validated in a prospective study, using sputum samples from patients with pneumonia. 568 patients were enrolled and the HIRA-TAN assay identified the causative pathogens with an accuracy of 96.7% for H. influenzae; 93.2% for Pseudomonas aeruginosa; 80.6% for Klebsiella pneumoniae; 90.9% for Moraxella catarrhalis; 87.5% for Escherichia coli; 78.1% for MRSA and 91.6% for S. pneumoniae. Overall the HIRA-TAN procedure was able to identify the causative pathogens of pneumonia in 60% of the cases. Additionally, this procedure was able to determine when the pneumonia-causing organism was a commensal organism or a foreign organism in a single assay. The HIRA-TAN approach yielded reproducible results and provided valuable information to plan the course of treatment of pneumonia. Through the rapid identification of the causative pathogens, the HIRA-TAN will promote targeted treatments for pneumonias. Clinical Trials Registration: UMIN000001694. © 2013 Published by Elsevier Ltd.


Ohta S.,Ibaraki Prefectural Central Hospital | Ohta S.,Kan Etsu Hospital | Cho Y.,Ibaraki Prefectural Central Hospital | Oshima S.,Josai University | And 3 more authors.
Oncology Letters | Year: 2012

We report the case of a woman who developed acute thrombocytopenia with hemorrhagic diathesis during adjuvant treatment of colorectal adenocarcinoma with oxaliplatin, 5-fluorouracil and leucovorin. A 55-year-old woman started adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin (mFOLFOX6). Prior to starting the 12th course of chemotherapy, a complete blood cell count showed the following values: neutrophils 1800/mm 3, platelets 136,000/m 3 and hemoglobin 11.1 g/dl. A blood count revealed that the platelet levels had dropped to 35,000/mm 3, with no significant changes in hemoglobin levels following the course. The administration of corticosteroids was begun and the platelet number was recovered. Clinicians should be aware of the possibility of oxaliplatin-induced hematological emergencies during the treatment of colorectal cancer patients in order to optimize supportive treatment and avoid toxic mortality.


Yamamoto T.,University of Tokyo | Yasuno N.,University of Tokyo | Yasuno N.,Kan etsu Hospital | Katada S.,University of Tokyo | And 8 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

The aim of the study was to quantitatively predict the clearance of three antibiotics, amikacin, vancomycin, and teicoplanin, during continuous hemodiafiltration (CHDF) and to propose their optimal dosage in patients receiving CHDF. For this goal, in vitro CHDF experiments with a polyacrylonitrile (PAN) membrane were first performed using these antibiotics, and then the clearances were compared with in vivo CHDF situations determined in 16 critically ill patients. The in vitro CHDF clearances were described as the product of the outflow rate of a drain (Q outflow) and the drug unbound fraction in artificial plasma, indicating that drug adsorption to the PAN membrane has minor effect on drug clearance in our settings. The observed in vivo clearances also agreed very well with the predicted values, with a product of Q outflow and plasma unbound fraction, when residual creatinine clearance (CL CR) was taken into account (within a range of 0.67- to 1.5-fold for 15 of 16 patients). Based on these results, a nomogram of the optimized dosages of amikacin, vancomycin, and teicoplanin was proposed, and it was evident that Q outflow and residual CL CR are major determinants of the dosage and dosing interval for these antibiotics. Although the applicability needs to be confirmed with another type of membrane or higher Q outflow, our nomogram can help determine the dosage setting in critically ill patients receiving CHDF. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Kasuya N.,Josai University | Ohta S.,Kan Etsu Hospital | Takanami Y.,Otsuma Women's University | Kawai Y.,Louis Pasteur Center for Medical Research | And 3 more authors.
Experimental and Therapeutic Medicine | Year: 2015

Low glycemic index (GI) food and postprandial exercise are non-drug therapies for improving postprandial hyperglycemia. The present randomized, crossover study investigated the effect of low GI food combined with postprandial exercise on postprandial blood glucose level, oxidative stress and antioxidant capacity. A total of 13 healthy subjects were each used in four experiments: i) rice only (control), ii) salad prior to rice (LGI), iii) exercise following rice (EX) and iv) salad prior to rice and exercise following rice (MIX). The blood glucose level, oxidative stress and antioxidant capacity were then measured. At 60 min after the meal, the blood glucose level was observed to be increased in the MIX group compared with that in the LGI group. Furthermore, at 180 min, the antioxidant capacity was found to be reduced in the MIX group compared with those of the LGI and EX groups. These findings suggest that low GI food combined with postprandial exercise does not improve postprandial hyperglycemia. It may be necessary to establish optimal timing and intensity when combining low GI food with postprandial exercise to improve postprandial hyperglycemia. © 2015, Spandidos Publications. All rights reserved.


PubMed | Kan Etsu Hospital and Yamagata Tokushukai Hospital
Type: Journal Article | Journal: Current urology | Year: 2014

We describe the effective use of the bipolar vessel-sealing device: LigaSure for the division of the internal spermatic vessels in a laparoscopic varicocelectomy. A total of 52 males with varicocele (left-side n = 49, and bilateral n = 3) were included in this study. Blunt dissection was used to isolate the packet of spermatic vessels. The packet of spermatic vessels was divided using a bipolar diathermy system, the LigaSure Precise. It was clear that the operative time was significantly reduced compared to the method using clips, which was done before the development of this kind of device. In another experiment to examine the effect of vessel sealing, it was confirmed that the LigaSure has performance comparable to the clips. Despite the result that the Harmonic scalpel was less effective in vessel sealing, our study found it difficult to determine which is superior, LigaSure or clips, in terms of operative time, relapse rate and complication.


PubMed | Minami Cho Clinic, Kan Etsu Hospital and Yamagata Tokushukai Hospital
Type: Journal Article | Journal: Experimental and therapeutic medicine | Year: 2013

Several clinically approved recombinant erythropoietin (rEPO) preparations, such as epoetin-, epoetin- and the epoetin- derivative, darbepoetin-, have been commercially produced. Since the expiration of patent protection, a number of novel rEPO biosimilars have been approved on the world market. In 2010, epoetin-, which is biosimilar to epoetin-, was clinically approved. Epoetin- is a biopharmaceutical product that is based on serum-free media following master cell bank preparation. The present study analyzes the results obtained during a six-month observation period, in which the administration of epoetin- was switched to that of epoetin-. In a cohort of patients receiving chronic dialysis, who were clinically in a state of relative calm and were in control of their renal anemia, it was possible to sustain good control of the anemia by reducing the frequency of the epoetin- administration from the conventional and empirically determined three times a week to twice a week, and further to once a week. Furthermore, the good control was maintained upon changing from the administration of epoetin- to that of epoetin-. Moreover, three months subsequent to this switch, the degree of instability observed among the patients had decreased. Despite the fact that the situation following the changeover requires further investigation, it may be concluded that the results obtained in this study are indicative of the clinical equivalence and efficacy of epoetin-.


PubMed | Otsuma Women's University, Louis Pasteur Center for Medical Research, Kan Etsu Hospital and Josai University
Type: Journal Article | Journal: Experimental and therapeutic medicine | Year: 2015

Low glycemic index (GI) food and postprandial exercise are non-drug therapies for improving postprandial hyperglycemia. The present randomized, crossover study investigated the effect of low GI food combined with postprandial exercise on postprandial blood glucose level, oxidative stress and antioxidant capacity. A total of 13 healthy subjects were each used in four experiments: i) rice only (control), ii) salad prior to rice (LGI), iii) exercise following rice (EX) and iv) salad prior to rice and exercise following rice (MIX). The blood glucose level, oxidative stress and antioxidant capacity were then measured. At 60 min after the meal, the blood glucose level was observed to be increased in the MIX group compared with that in the LGI group. Furthermore, at 180 min, the antioxidant capacity was found to be reduced in the MIX group compared with those of the LGI and EX groups. These findings suggest that low GI food combined with postprandial exercise does not improve postprandial hyperglycemia. It may be necessary to establish optimal timing and intensity when combining low GI food with postprandial exercise to improve postprandial hyperglycemia.


PubMed | Red Cross, Chichibu Hospital, Aoki Hospital, Saitama University and 5 more.
Type: Comparative Study | Journal: Journal of gastroenterology and hepatology | Year: 2015

An intention-to-treat prospective randomized study was carried out to compare the potentiation of antiviral efficacies between cholecalciferol, non-activated vitamin D3 supplement, and alfacalcidol, activated 1-Hydroxyvitamin D3 [1 (OH)-vitamin D3].Chronic hepatitis patients with genotype 1b hepatitis C virus (HCV) infection showing serum HCV-RNA levels greater than 5 Log IU/mL received oral administration of cholecalciferol (2000IU/day) or alfacalcidol (0.5g/day) for 4 weeks, and then they were given pegylated interferon (Peg-IFN)-2a plus ribavirin therapy in combination with either vitamin D3 for 48 or 72 weeks according to the response-guided manner.A total of 36 patients were evaluated. Serum 25-hydroxyvitamin D3 [25(OH)-D3] levels were increased only in patients in the cholecalciferol group during the lead-in vitamin D administration, and the levels at 4 weeks were higher in these patients than in those in the alfacalcidol group (P<0.001), while serum 1,25-dihydroxyvitamin D3 [1,25(OH)2 -D3] levels were not different between both groups. Rapid virological response was obtained in six (33%) patients in the cholecalciferol group; the ratio was higher than that in the alfacalcidol group (one patient; 6%, P<0.05). Serum HCV-RNA level decline at 4 weeks of combined Peg-IFN-2a plus ribavirin therapy compared with the baseline levels were greater in the cholecalciferol group (4.6 Log IU/mL) than in the alfacalcidol group (3.5 Log IU/mL) (P<0.05), when four patients showing null response to the therapy was excluded. However, both complete early virological response and sustained viral response rates were not different between both groups.Cholecalciferol produced superior potentiation of the antiviral activity than alfacalcidol only during the initial periods of combined Peg-IFN-2a plus ribavirin therapy through upregulation of serum 25(OH)-D3 levels.


PubMed | Kan etsu Hospital and Musashino University
Type: Journal Article | Journal: Journal of pharmaceutical health care and sciences | Year: 2016

Sivelestat, a neutrophil elastase inhibitor, was previously approved in Japan for the treatment of acute lung injury associated with systemic inflammatory response syndrome. However, sivelestat produced inconsistent therapeutic benefits. This study aimed to identify factors predicting the therapeutic effects of sivelestat.We enrolled 53 mechanically ventilated patients who received sivelestat. The patients were classified as effective (n=28) if they were weaned from the ventilator within 28days, or as ineffective groups (n=25). Patient characteristics were compared between these groups and multivariate logistic regression analysis was used to identify predictive factors. A validation study was then conducted in sivelestat-free patients.A high red blood cell count and low hydrogen ion concentration were significantly associated with a higher ventilator weaning rate in patients receiving sivelestat. The validation study revealed that the hydrogen ion concentration value also significantly associated with ventilator weaning in patients who did not receive sivelestat.Although hydrogen ion concentration was inversely associated with the ventilator weaning rate, it did not predict sivelestat efficacy. This study indicated that acute lung injury patients with a high red blood cell count would derive the most benefit from sivelestat administration.

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