Yasuhiro Yamamoto

Nippon Medical School, Edo, Tōkyō, Japan

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Publications (244)507.4 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Sivelestat, a neutrophil elastase inhibitor, has been approved in Japan for the treatment of patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome (SIRS). The Pharmaceuticals and Medical Devices Agency (PMDA) has ordered to conduct a postmarket clinical study in order to reevaluate the efficacy and safety of Sivelestat in actual clinical settings in Japan. According to the PMDA's order, we evaluated the efficacy and safety of Sivelestat in Japanese patients with ALI associated with SIRS using ventilator-free days (VFD) as the primary endpoint. The surrogate endpoints are ventilator-weaning rate, ICU discharge rate, and 180-day survival rate. Study design was an open-label, non-randomized, multi-center clinical trial. Sivelestat was intravenously administered at 0.2 mg/kg/h continuously for a maximum of 14 days. Sivelestat group and control group were compared by adjusting the outcome values using an inverse probability of treatment weighted method based on the propensity scores. Four hundred and four Sivelestat group patients and 177 control group patients were enrolled. The adjusted mean number of VFD was 15.7 and 12.1 in the Sivelestat group and control group, respectively (P = 0.0022). Both the adjusted ventilator-weaning rate and ICU discharge rate were significantly higher in the Sivelestat group than in the control group (P = 0.0028 and P = 0.019, respectively). The adjusted 180-day survival rate was significantly higher in the Sivelestat group than in the control group (71.8 percent vs. 56.3 percent). Sivelestat contributed to early weaning from the mechanical ventilation, while showing no negative effect on the long-term outcomes of ALI associated with SIRS. The results of this study suggest the clinical usefulness of Sivelestat in this patient population.
    No preview · Article · Apr 2011 · Pulmonary Pharmacology & Therapeutics
  • Keisuke Kato · Yasuhiro Yamamoto · Hiroyuki Akita
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Dec 2010 · ChemInform
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    ABSTRACT: To investigate treatment effects of thrombomodulin alfa (TM-α) in patients with disseminated intravascular coagulation (DIC) having infection as the underlying disease, retrospective subanalysis of a double-blind, randomized controlled phase 3 trial was conducted. In the phase 3 trial, 227 DIC patients (full-analysis set) having infection and/or hematologic malignancy as the underlying disease received either TM-α (0.06 mg·kg for 30 min once daily) or heparin (8 U·kg·h for 24 h) for 6 days using the double-dummy method. Among these patients, 147 patients with noninfectious comorbidity leading to severe thrombocytopenia (e.g., hematologic malignancy, or aplastic anemia) were excluded from the present analysis, and 80 patients with infectious disease and DIC were extracted and subjected to the present retrospective subanalysis. Disseminated intravascular coagulation resolution rates were determined using the DIC diagnostic criteria for critically ill patients at 7 days, and mortality rates were evaluated at 28 days. In the TM-α and heparin groups, DIC resolution rates were 67.5% (27/40) and 55.6% (20/36), and 28-day mortality rates were 21.4% (9/42) and 31.6% (12/38), respectively. Mortality rates of patients who recovered from DIC were 3.7% (1/27) in the TM-α group and 15% (3/20) in the heparin group. These results suggest TM-α may be valuable in the treatment of DIC associated with infection.
    No preview · Article · Nov 2010 · Shock (Augusta, Ga.)
  • Keisuke Kato · Yasuhiro Yamamoto · Hiroyuki Akita

    No preview · Article · Oct 2010 · ChemInform
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    ABSTRACT: Gravimetric validation of single-indicator extravascular lung water (EVLW) and normal EVLW values has not been well studied in humans thus far. The aims of this study were (1) to validate the accuracy of EVLW measurement by single transpulmonary thermodilution with postmortem lung weight measurement in humans and (2) to define the statistically normal EVLW values. We evaluated the correlation between pre-mortem EVLW value by single transpulmonary thermodilution and post-mortem lung weight from 30 consecutive autopsies completed within 48 hours following the final thermodilution measurement. A linear regression equation for the correlation was calculated. In order to clarify the normal lung weight value by statistical analysis, we conducted a literature search and obtained the normal reference ranges for post-mortem lung weight. These values were substituted into the equation for the correlation between EVLW and lung weight to estimate the normal EVLW values. EVLW determined using transpulmonary single thermodilution correlated closely with post-mortem lung weight (r = 0.904, P < 0.001). A linear regression equation was calculated: EVLW (mL) = 0.56 × lung weight (g) - 58.0. The normal EVLW values indexed by predicted body weight were approximately 7.4 ± 3.3 mL/kg (7.5 ± 3.3 mL/kg for males and 7.3 ± 3.3 mL/kg for females). A definite correlation exists between EVLW measured by the single-indicator transpulmonary thermodilution technique and post-mortem lung weight in humans. The normal EVLW value is approximately 7.4 ± 3.3 mL/kg. UMIN000002780.
    Full-text · Article · Sep 2010 · Critical care (London, England)
  • Keisuke Kato · Maki Tanaka · Yasuhiro Yamamoto · Hiroyuki Akita
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Jun 2010 · ChemInform
  • Tomoaki Tanase · Yasuhiro Yamamoto
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · May 2010 · ChemInform
  • Kazuyoshi Sugano · Tomoaki Tanase · Kimiko Kobayashi · Yasuhiro Yamamoto
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Mar 2010 · ChemInform

  • No preview · Article · Mar 2010 · The Journal of trauma
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    ABSTRACT: The large number casualties caused by the 1995 Great Hanshin and Awaji Earthquake created a massive demand for medical care. However, as area hospitals also were damaged by the earthquake, they were unable to perform their usual functions. Therefore, the care capacity was reduced greatly. Thus, the needs to: (1) transport a large number of injured and ill people out of the disaster-affected area; and (2) dispatch medical teams to perform such wide-area transfers were clear. The need for trained medical teams to provide medical assistance also was made clear after the Niigata-ken Chuetsu Earthquake in 2004. Therefore, the Japanese government decided to establish Disaster Medical Assistance Teams (DMATs), as "mobile, trained medical teams that rapidly can be deployed during the acute phase of a sudden-onset disaster". Disaster Medical Assistance Teams have been established in much of Japan. The provision of emergency relief and medical care and the enhancement and promotion of DMATs for wide-area deployments during disasters were incorporated formally in the Basic Plan for Disaster Prevention in its July 2005 amendment. The essential points pertaining to DMATs were summarized as a set of guidelines for DMAT deployment. These were based on the results of research funded by a Health and Labour Sciences research grant from the, Labour and Welfare (MHLW) of the Ministry of Health. The guidelines define the basic procedures for DMAT activities-for example: (1) the activities are to be based on agreements concluded between prefectures and medical institutions during non-emergency times; and (2) deployment is based on requests from disaster-affected prefectures and the basic roles of prefectures and the MHLW. The guidelines also detail DMAT activities at the disaster scene of the, support from medical institutions, and transportation assistance including "wide-area" medical transport activities, such as medical treatment in staging care units and the implementation of medical treatment onboard aircraft. Japan's DMATs are small-scale units that are designed to be suitable for responding to the demands of acute emergencies. Further issues to be examined in relation to DMATs include expanding their application to all prefectures, and systems to facilitate continuous education and training.
    Full-text · Article · Dec 2009 · Prehospital and disaster medicine: the official journal of the National Association of EMS Physicians and the World Association for Emergency and Disaster Medicine in association with the Acute Care Foundation

  • No preview · Article · Mar 2009 · The Journal of trauma
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    ABSTRACT: 1. Sivelestat sodium hydrate (sivelestat), a neutrophil elastase inhibitor, is used to treat acute lung injury associated with systemic inflammatory response syndrome, but its effects have not been described for endotoxaemia. In the present study, we examined the effects of a continuous infusion of sivelestat on intestinal mechanical activity and blood pressure using an endotoxaemic model in conscious, unrestrained guinea-pigs. 2. Guinea-pigs underwent laparotomy while anaesthetized and were implanted with a force transducer sutured onto the taenia caecum. With this transducer, changes in tension in the intestinal longitudinal muscle were measured continuously via telemetry. Catheters were inserted into the carotid artery and jugular vein, were tunnelled subcutaneously and were accessed from the back of the neck. These catheters were connected to a cannula swivel and were used to monitor arterial pressure as well as to administer drugs i.v. in conscious, unrestrained guinea-pigs. Twenty hours after surgery, guinea-pigs received a single dose of lipopolysaccharide (LPS; 0.3 mg/kg, i.p.) 10 min after the start of a continuous 2 h i.v. infusion of sivelestat (30 mg/kg per h) or vehicle (saline). Elastase activity before and after sivelestat or vehicle administration was measured spectrometrically using a specific synthetic substrate. 3. We confirmed that intestinal longitudinal muscle tension decreased 2-3 h after LPS administration in the control group, with a concurrent decline in blood pressure. In guinea-pigs treated with sivelestat, the LPS-induced decreases in muscle tension and blood pressure were significantly reduced. In LPS-treated control guinea-pigs, serum elastase activity was elevated and this increase was significantly attenuated by administration of sivelestat. 4. The findings from the present study suggest that sivelstat can effectively reduce intestinal dysfunction and attenuate LPS-induced decreases in blood pressure in endotoxaemia.
    No preview · Article · Aug 2008 · Clinical and Experimental Pharmacology and Physiology
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    ABSTRACT: Procalcitonin serum level has been recommended as a new marker of bacterial infectious diseases. The aim of this prospective, multicenter study was to determine the clinical usefulness of procalcitonin in differentiating patients with sepsis from those with severe sepsis. Eighty-two patients were enrolled: 20 without systemic inflammatory response syndrome (SIRS), 9 with SIRS, 34 with sepsis, and 19 with severe sepsis. The patients with severe sepsis had significantly higher procalcitonin levels (median, 36.1 ng/ml) than those with sepsis (median, 0.6 ng/ml). With a procalcitonin cutoff value of 2.0 ng/ml, sensitivity for the detection of severe sepsis and specificity for the detection of sepsis were 94.7% and 78.1%, respectively. A good correlation was found between the serum procalcitonin level and the Sepsis-Related Organ Failure Assessment (SOFA) score (r = 0.680), although no correlation was found between the C-reactive protein (CRP) level and the SOFA score. In conclusion, the procalcitonin serum level may be useful not only for aiding the diagnosis of sepsis but also for discriminating between sepsis and severe sepsis.
    No preview · Article · Jul 2008 · Journal of Infection and Chemotherapy
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    ABSTRACT: Recently, the existence of a relationship was reported between the severity of lung injury and the serum level of F2-isoprostane, a known oxidative stress marker. Recent reports have suggested that direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX) may improve the oxygenation in patients with acute lung injury and acute respiratory distress syndrome. Because cases of septic shock associated with respiratory diseases have poor outcomes, we selected cases of septic shock associated with respiratory disease to review the characteristics of the treatment-resistant cases. We treated 13 septic shock cases due to respiratory disease using DHP-PMX. The patients were separated into 2 groups for analysis from oxygenation effect immediately after DHP-PMX: A group (7 cases) PaO2/FiO2 ratio increased more than 20%; B group (6 cases) PaO2/FiO2 ratio did not increase more than 20%. Factors were measured before DHP-PMX. The average Acute Physiology and Chronic Health Evaluation II score was 31.2 +/- 9.4, and the average sequential organ failure assessment score was 15.1 +/- 5.3 before DHP-PMX. Four patients survived and 9 died. Only the F2-Isoprostane level was significantly high in B group (p = 0.0228). A relationship between F2-Isoplostane and rebellious cases by DHP-PMX in severe respiratory disease patients became clear.
    No preview · Article · Jul 2008 · ASAIO journal (American Society for Artificial Internal Organs: 1992)
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    ABSTRACT: Iron-incorporated zeolites were successfully synthesized at a low temperature such as 80°C by choosing appropriate starting materials and characterized by inductively coupled plasma atomic emission spectrometry (ICP-AES), wide-angle X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and magnetic susceptibility. ICP-AES showed␣that Fe component can be readily incorporated␣up to a maximum extent of Fe substitution, Fe/(Fe + Al) × 100 = 22.7%. XRD measurements suggested that the zeolites obtained have a crystal structure of gismondine type. The characterizations identified that the Fe component present in the products is all incorporated into the zeolite framework. The ammonia and water desorption profiles were compared for Fe-free and 22.7% Fe-zeolites ion-exchanged for NH4+ by means of TG-MS and DSC. The ammonia desorption peak temperatures considerably shifted toward lower temperatures by the introduction of Fe, suggesting decreased solid acidity. DSC thermograms of the as-synthesized gismondines revealed that they do not contain free water (i.e., water not coordinated to cations) in the pores irrespective of the Fe content. The enhanced catalytic reactivity of the Fe-incorporated gismondines was also confirmed from the decomposition of hydrogen peroxide. An apparent activation energy of 43 kJ mol−1 was obtained independent of the Fe contents in zeolites. This value was much lower than 70 kJ mol−1 for the same reaction in the homogeneous solution containing iron alum as a reference sample.
    No preview · Article · Feb 2008 · Journal of Porous Materials
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    ABSTRACT: 1. Direct haemoperfusion through a network of fibres immobilizing polymyxin B (PMX-B) is used for the treatment of septic shock, but the mechanism underlying its clinical benefits remains unclear. The aims of the present study were to assess the actions of direct haemoperfusion through fibres immobilizing PMX-B (PMX-DHP) on the effects of exogenously administered endotoxin in conscious guinea-pigs and to examine the difference in the effects of heparin compared with nafamostat mesilate (NM) used as an anticoagulant. Although nafamostat is widely used in Japan, the agent cannot necessarily be used elsewhere in the world. Therefore, the study aimed to investigate and elucidate the effectiveness of NM compared with heparin. 2. Colonic motion was monitored continuously via telemetry using a force transducer attached to the taenia caecum, whereas blood pressure was monitored using a carotid artery catheter. To establish a haemoperfusion circuit in each freely moving and conscious guinea-pig, catheters were implanted in the carotid artery and the jugular vein, tunnelled subcutaneously, exteriorized at the back of the neck in contact with a lightweight tethering spring and attached to a swivel device at the top of the cage. On the day after the operation, lipopolysaccharide (LPS; Escherichia coli, O111:B4; 1 mg/kg) was administered i.v. and PMX-DHP was conducted for 2 h. Heparin (50 IU/h) or NM (0.4 mg/h) was used as the anticoagulant. Furthermore, guinea-pigs were administered a lethal dose of LPS (10 mg/kg) and the survival rate was examined for animals undergoing PMX-DHP compared with control animals. 3. In guinea-pigs treated with PMX-DHP, relaxation of colonic longitudinal muscle caused by LPS was significantly suppressed, as were decreases in blood pressure. Of the two anticoagulants used, NM was more effective than heparin. In addition, PMX-DHP significantly increased the survival rate of guinea-pigs that received potentially lethal doses of LPS. 4. In conscious and unrestrained guinea-pig endotoxaemia model, PMX-DHP significantly improved intestinal paralysis and decreases in blood pressure. These effects were augmented more by NM than by heparin when an anticoagulant was used in the perfusion process. These findings suggest that haemoperfusion using PMX and NM performed in the early stage of endotoxaemia is an effective treatment.
    No preview · Article · Feb 2008 · Clinical and Experimental Pharmacology and Physiology

  • No preview · Article · Jan 2008 · Nihon Kyukyu Igakukai Zasshi
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    ABSTRACT: Septic shock is a condition associated with diffuse coagulopathy and multiple organ failure, and frequently ends in death. Direct hemoperfusion using a polymyxin B-immobilized fiber column (DHP-PMX) was first developed in Japan in 1994 and has since been used for the treatment of septic shock. On the other hand, the effectiveness of continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA- CHDF) for critically ill patients has also been reported. We treated 27 septic shock patients by DHP-PMX. The patients, except for the nine in whom CHDF was not performed after DHP-PMX, were divided into two groups: namely, a group in which PMMA-CHDF therapy was added after DHP-PMX (11 cases), and a group in which continuous hemodiafiltration using a polyacrylonitrile membrane hemofilter (PAN-CHDF) therapy was added after DHP-PMX (7 cases). The outcomes in the two groups were compared. The average Acute Physiology and Chronic Health Evaluation (APACHE) II score and the average sepsis-related organ failure assessment (SOFA) score were not significantly different between the two groups. The PMMA-CHDF group showed significantly better outcomes, with significant improvements of the serum PAI-1, protein C, IL-6 and N-arachidonoylethanolamine (AEA) levels. We conclude that PMMA-CHDF may be more effective than PAN-CHDF in the management of septic shock.
    No preview · Article · Jan 2008 · ASAIO journal (American Society for Artificial Internal Organs: 1992)
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    ABSTRACT: Elevated serum levels of thrombomodulin (TM) and von Willebrand factor (vWf) are good indicators of injury and activation of cerebral endothelium in patients with severe simple head injury. The present study evaluated cerebral endothelial injury or activation as the serum levels of TM and vWf in elderly and younger patients with similar brain trauma, to evaluate the primary parenchymal injury of the brain. Patients with head injury were classified into the young group (16-30 years), the middle-aged group (31-65 years), and the elderly group (over 66 years). There was no difference in Glasgow Coma Scale on admission between the three groups. The serum levels of TM and vWf at 2 hours after injury were significantly higher in the elderly group than in the other groups. However, the serum levels of TM and vWf were not significantly different at 3 and 7 days after injury. Cerebral endothelial activation and injury were significantly higher in elderly patients just after head injury than in younger patients, which suggests that greater sensitivity to endothelial injury and activation may be important in the worse outcome after head injury in elderly patients compared with younger patients.
    No preview · Article · Oct 2007 · Neurologia medico-chirurgica
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    ABSTRACT: Direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX; Toray Industries Inc., Tokyo, Japan) was first developed in 1994 and has since been used for the treatment of septic shock. Positive clinical data, such as an increase in systolic blood pressure (SBP) and an improved Pao2/Fio2 ratio, have also been reported. We treated 27 septic shock patients using DHP-PMX. The patients were separated into two groups for analysis: those whose Pao2/Fio2 ratio increased after DHP-PMX (9 cases) and those whose Pao2/Fio2 ratio did not increase after DHP-PMX (18 cases). The patients were also separated into two other groups for analysis: those whose SBP increased by more than 30 mm Hg immediately after DHP-PMX (15 cases) and those whose SBP did not increase by more than 30 mm Hg after DHP-PMX (12 cases). The Pao2/Fio2 ratio increased significantly after DHP-PMX in the groups showing improved 2AG and PAI-1 levels (p = 0.0040). The SBP increased significantly in the group showing improved HMGB-1 levels (p < 0.0001). We observed a relationship between hemodynamic improvement and increase of the serum HMGB-1 levels and between improvement of respiratory functions and increase of the serum 2-AG and PAI-1 levels in septic shock patients treated with DHP-PMX.
    No preview · Article · Sep 2007 · ASAIO journal (American Society for Artificial Internal Organs: 1992)

Publication Stats

3k Citations
507.40 Total Impact Points

Institutions

  • 1981-2011
    • Nippon Medical School
      • • Department of Emergency and Critical Care Medicine
      • • Department of Neurosurgery
      Edo, Tōkyō, Japan
  • 2009-2010
    • Tokyo Rinkai Hospital
      Edo, Tōkyō, Japan
  • 1993-2010
    • Nara Women's University
      • Department of Chemistry
      Nara, Nara, Japan
  • 1991-2010
    • Toho University
      • • Faculty of Pharmaceutical Sciences
      • • Department of Chemistry
      • • Faculty of Science
      Edo, Tōkyō, Japan
  • 2004-2007
    • Ministry of Health, Labour and Welfare - Japan
      Edo, Tōkyō, Japan
  • 2006
    • SickKids
      • Division of Neurosurgery
      Toronto, Ontario, Canada
  • 2001-2005
    • Sapporo Medical University
      • Department of Traumatology and Critical Care Medicine
      Sapporo, Hokkaidō, Japan
  • 1997
    • Funabashi Municipal Medical Center
      Hunabasi, Chiba, Japan
  • 1986
    • RIKEN
      Вако, Saitama, Japan