Naoya Matsumoto

Iwate Medical University, Morioka-shi, Iwate-ken, Japan

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Publications (16)26.48 Total impact

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    ABSTRACT: The endotoxin activity assay (EAA) is a FDA-approved blood endotoxin assay that is reported as a useful tool for the diagnosis of gram-negative bacterial infection. However, discrepancies between the results of the EAA and those of the limulus amebocyte lysate (LAL) assay have been reported. Thus, we verified these methods. Blood was incubated with anti-endotoxin antibody, the resultant polymorphonuclear activation to produce oxidants was measured and the EAA level calculated. As a reference endotoxin assay, we used an endotoxin-specific LAL assay. Significant increases in plasma LAL assay levels were observed only in patients with sepsis caused by gram-negative bacterial infections, whereas higher EAA levels were observed in almost all the sepsis cases and the SIRS cases, especially those with acute pancreatitis. Graded amounts of LPS (1-10,000 pg/ml) were spiked into normal blood to obtain dose-response curves: a good dose-response curve, from 1 to 1,000 pg/ml, was obtained for the LAL assay. A good dose-response curve was barely obtained for the EAA; the lowest detection limit seemed to be 1,000 pg/ml. Addition of methylprednisolone decreased the EAA levels. Interleukin-8 (IL-8) induced elevation in EAA levels when IL-8 was added to volunteers' blood samples. Overall, the EAA kit could not measure clinically relevant doses of endotoxin. Because IL-8 induced an increase in EAA level, it is suggested that the EAA level reflects the primed state of polymorphonuclear leukocytes.
    Journal of Infection and Chemotherapy 03/2013; · 1.55 Impact Factor
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    ABSTRACT: We focused our attention on the endotoxin present within and on the surface of white blood cells and attempted to establish a new sample preparation method for endotoxin assays in leukocyte-rich plasma (LRP), taking advantage of the erythrocyte-aggregating property of hydroxyethyl starch. We used an endotoxin-specific turbidimetric kinetic assay, which is the conventional method used to assay endotoxin levels in platelet-rich plasma (PRP). Then, we comparatively assessed the assay results obtained with the endotoxin assay using PRP and LRP. It was found that the sensitivity of endotoxin assay in LRP was 88.5 %, which was superior to 73.1 % of the sensitivity in PRP in the diagnosis of infections caused by gram-negative bacteria. These results suggest that our newly developed LRP endotoxin assay may contribute to an improvement in the rate of sepsis diagnosis.
    Journal of Infection and Chemotherapy 02/2013; · 1.55 Impact Factor
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    ABSTRACT: In the diagnosis of sepsis, the sensitivity of the endotoxin assay using platelet-rich plasma (PRP) is not as high as expected. In the endotoxin assay using PRP, endotoxin occurring within and on the surface of white blood cells cannot be measured. Thus, we devised a method of preparing leukocyte-rich plasma (LRP) using hydroxyethyl starch (HES) in order to improve the endotoxin assay. The endotoxin concentration was measured by an endotoxin-specific Limulus amebocyte lysate assay method: turbidimetric kinetic assay. Only 1% of erythrocytes were recovered in LRP without the hemolysis of erythrocytes. Endotoxin contents in PRP obtained from blood incubated for 0, 30, 60, 120, and 180 min at 37 degrees C in the presence of lipopolysaccharide (50 pg/ml in a final concentration) were 1.18, 1.23, 1.23, 1.39, and 1.25 times higher (mean value from three bloods) than that in PRP, respectively. Thus, the superiority of the sensitivity of the LRP-based endotoxin assay over the PRP-based assay was identified. Our newly devised assay method may contribute to improvement of the diagnosis rate of endotoxemia in sepsis.
    Rinsho byori. The Japanese journal of clinical pathology 11/2012; 60(11):1045-52.
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    ABSTRACT: Septic arthritis of the sternoclavicular joint (SCJ) is extremely rare, and usually appears to result from hematogenous spread. Predisposing factors include immunocompromising diseases such as diabetes. A 61-year-old man with poorly controlled diabetes mellitus presented to our emergency department with low back pain, high fever, and a painful mass over his left SCJ. He had received two epidural blocks over the past 2 weeks for severe back and leg pain secondary to lumbar disc herniation. He did not complain of weakness or sensory changes of his lower limbs, and his bladder and bowel function were normal. He had no history of shoulder injection, subclavian vein catheterization, intravenous drug abuse, or focal infection including tooth decay. CT showed an abscess of the left SCJ, with extension into the mediastinum and sternocleidomastoid muscle, and left paraspinal muscle swelling at the level of L2. MRI showed spondylodiscitis of L3-L4 with a contiguous extradural abscess. Staphylococcus aureus was isolated from cultures of aspirated pus from his SCJ, and from his urine and blood. The SCJ abscess was incised and drained, and appropriate intravenous antibiotic therapy was administered. Two weeks after admission, the purulent discharge from the left SCJ had completely stopped, and the wound showed improvement. He was transferred to another ward for treatment of the ongoing back pain. Diabetic patients with S. aureus bacteremia may be at risk of severe musculoskeletal infections via hematogenous spread.
    BMC Emergency Medicine 06/2012; 12(1):7.
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    ABSTRACT: The purpose of this study was to investigate the relationship between the blood levels of interleukin (IL)-18 measured in the early stage of acute respiratory failure and the prognosis for patient survival. The study subjects were 38 patients with acute respiratory failure treated at our institution during the 4-year period from April 2004 to March 2008. The underlying clinical condition was defined as acute respiratory distress syndrome (ARDS; n = 12) or acute lung injury (ALI; n = 26). The serum levels of interleukin (IL)-18, IL-12, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assays. The ARDS group showed significantly higher serum levels of IL-18, IL-12, and TNF-α even at an early stage after disease onset compared with the ALI group. A negative correlation was noted between the PaO(2)/FIO(2) ratio (P/F ratio) and serum IL-18 level. Analysis of all 38 patients with ALI/ARDS revealed a 30-day mortality rate of 7.9 %, 60-day mortality rate of 15.8 %, and 90-day mortality rate of 18.4 %. The early-stage serum levels of IL-18, IL-12, and TNF-α were significantly higher in the non-survivors at 60 and 90 days, but not at 30 days, than in the corresponding survivors. The present data demonstrate an inverse correlation between serum IL-18 level and the P/F ratio, suggesting the possible involvement of IL-18 in the pathogenesis of respiratory failure in patients with ALI/ARDS. Early-stage serum IL-18, IL-12, and TNF-α levels appear to reflect the >60-day prognosis in patients with ALI/ARDS.
    Journal of Anesthesia 05/2012; 26(5):658-63. · 0.87 Impact Factor
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    ABSTRACT: A synthetic luminescent substrate method, using a mutant-type luciferase whose luminescence intensity is more than ten times as intense as the wild type, was developed recently. We conducted the first basic studies on clinical application of the novel endotoxin measurement method. We assessed and established measurement conditions, including reagent concentrations and reaction time, so that it would be possible to apply the luminescent synthetic substrate method proposed by Noda et al. to measurements in human blood. When we added lipopolysaccharide (LPS) to water, it was possible to measure LPS at a concentration of 0.1 pg/ml, whereas it was possible to measure LPS in tenfold diluted and heated plasma at a concentration of 1 pg/ml. When plasma was further diluted, inhibiting activity decreased considerably. Thus, it will be necessary to completely eliminate the inhibitor present in plasma. However, the shortest time after collecting the specimen in which it was possible to make measurements was 30-40 min, suggesting that if an assay is established, it will be possible to use the method as a novel blood endotoxin assay.
    Journal of Infection and Chemotherapy 05/2012; 18(3):370-7. · 1.55 Impact Factor
  • Critical Care 03/2012; 16(1). · 4.93 Impact Factor
  • Critical Care 10/2011; 15(3). · 4.93 Impact Factor
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    ABSTRACT: Endotoxin (Et) adsorption therapy with a column of polymyxin B-immobilized fibers (PMX) is effective in improving the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (PaO(2)/FiO(2) ratio) and increasing mean arterial blood pressure (MAP) in sepsis. S100A12 and soluble receptor for advanced glycation end product (sRAGE) are useful as early markers of acute lung injury. To investigate the effect of improving the PaO(2)/FiO(2) ratio by PMX-direct hemoperfusion (PMX-DHP) on production of S100A12 and sRAGE. Sepsis patients after surgery for perforation of the lower gastrointestinal tract were adopted as the subjects. We retrospectively reviewed the cases of 20 patients on mechanical ventilation and continuous administration of norepinephrine. We recorded PaO(2)/FiO(2) ratio, MAP, and norepinephrine doses. S100A12, sRAGE, and Et levels were measured before and after PMX-DHP. The PaO(2)/FiO(2) ratio and MAP improved significantly after PMX-DHP (p < 0.05). S100A12 and Et decreased significantly after PMX-DHP (p < 0.05). No differences were observed in sRAGE. S100A12 is useful as a marker that reflected improvement in the PaO(2)/FiO(2) ratio after PMX-DHP. We consider PMX-DHP to be useful as adjunctive therapy for sepsis that reduces the Et and corrects the pathology in the early stage.
    European Surgical Research 09/2011; 47(3):135-40. · 0.75 Impact Factor
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    ABSTRACT: Tight glucose control (TGC) using a sliding scale based on intermittent blood glucose measurements occasionally can have a fatal outcome as a result of insulin-induced hypoglycemia. The present study was undertaken to examine whether the use of an artificial pancreas to achieve TGC would be possible in postoperative patients with sepsis. The retrospective study was carried out as an exploratory study, focusing on the possibility of precise evaluation of the significance of TGC as a beneficial intervention by serological monitoring of various mediators. TGC was accomplished using an artificial pancreas (STG-22; (Nikkiso, Tokyo, Japan). The patients were divided into two groups: the TGC group (6 patients with sepsis in whom the target blood glucose level set at <150 mg/dl was attempted using the artificial pancreas), and the glucose control (GC) group (6 patients with sepsis in whom glucose control was attempted using a sliding scale; target blood glucose level was set at 200 mg/dl or lower). The mean blood glucose level was 129.7 ± 9.7 mg/dl in the TGC group and 200.9 ± 14.7 mg/dl in the GC group (P < 0.01, ANOVA). No hypoglycemia associated with the artificial pancreas was seen in any of the patients. The serum levels of S100A12 and HMGB-1 tended to decrease, and those of sRAGE tended to increase, in the TGC group. Further data collection from a larger number of cases would be expected to allow a precise assessment of TGC as a potentially beneficial intervention in sepsis patients.
    Journal of Infection and Chemotherapy 06/2011; 17(6):812-20. · 1.55 Impact Factor
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    ABSTRACT: CD14 is present in macrophage, monocyte, and granulocyte cells and their cell membranes, and it is said to be responsible for intracellular transduction of endotoxin signals. Its soluble fraction is present in blood and is thought to be produced in association with infections. It is called the soluble CD14-subtype (sCD14-ST), and in the following text it is referred to by its generic name, presepsin. We have previously reported that presepsin is produced in association with infection and that it is specifically expressed in sepsis. In the present study we developed a new rapid diagnostic method by using a chemiluminescent enzyme immunoassay that allowed making automated measurements in a shorter time. The results of using this method to measure presepsin values in different pathological conditions were normal, 294.2 ± 121.4 pg/ml; local infection, 721.0 ± 611.3 pg/ml; systemic inflammatory response syndrome, 333.5 ± 130.6 pg/ml; sepsis, 817.9 ± 572.7 pg/ml; and severe sepsis, 1,992.9 ± 1509.2 pg/ml; the presepsin values were significantly higher in patients with local infection, sepsis, and severe sepsis than in patients who did not have infection as a complication. In a comparative study with other diagnostic markers of sepsis based on ROC curves, the area under the curve (AUC) of presepsin was 0.845, and greater than the AUC of procalcitonin (PCT, 0.652), C-reactive protein (CRP, 0.815), or interleukin 6 (IL-6, 0.672). In addition, a significant correlation was found between the APACHE II scores, an index of disease severity, and the presepsin values, suggesting that presepsin values can serve as a parameter that closely reflects the pathology.
    Journal of Infection and Chemotherapy 05/2011; 17(6):764-9. · 1.55 Impact Factor
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    ABSTRACT: Glucose control is essential to avoid hypoglycemia in postoperative patients. To conduct a preliminary examination to evaluate the feasibility of the use of an artificial pancreas for glucose control as well as the accuracy of assessment by the artificial pancreas of the insulin dose required. Glucose control using an artificial pancreas was undertaken in 8 postoperative sepsis patients. The blood glucose level was set at 80-150 mg/dl. Blood glucose levels over time, insulin dose requirements, and occurrence of hypoglycemia (≤40 mg/dl) were recorded for each patient. The patients were divided into 2 groups based on the total insulin dose they received over the 7 days (HG, n = 4: consisting of patients who required a higher insulin dose; LG, n = 4: patients who required a lower insulin dose). The data of the 2 groups were analyzed retrospectively. The blood glucose level before glucose control was 203.3 ± 9.9 mg/dl and could be controlled in all patients to within the target range. No hypoglycemia events were recorded for any of the patients. The insulin dose in the HG and LG groups was 21,824.8 ± 6,030.4 and 6,254.5 ± 3,402.3 mU/kg (p < 0.05). Accurate glucose control could be achieved with the artificial pancreas.
    European Surgical Research 01/2011; 47(1):32-8. · 0.75 Impact Factor
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    ABSTRACT: We present a 19-year-old man who excreted green urine after propofol infusion. The patient was admitted to our hospital for injuries sustained in a traffic accident and underwent surgery. After starting continuous infusion of propofol for postoperative sedation, his urine became dark green. Serum total bilirubin and urine bilirubin were both elevated. We believe that the green discoloration of the urine was caused by propofol infusion and was related to impaired enterohepatic circulation and extrahepatic glucuronidation in the kidneys.
    Case reports in emergency medicine. 01/2011; 2011:242514.
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    ABSTRACT: The purpose of this study was to assess lipopolysaccharide (LPS)-stimulated cytokine production in the presence of linezolid (LZD) in comparison with the drug effect on the plasma endotoxin level. Peripheral venous whole-blood samples collected from five healthy subjects were stimulated with 10 microg/ml of LPS. LZD was then added to the LPS-stimulated blood samples at concentrations of 0, 2, 4, and 15 microg/ml , followed by incubation for 24 h at 37 degrees C in a 5% CO(2)-95% air atmosphere. Supernatants of the resultant cultures were assayed to determine the levels of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-10, monocyte chemoattractant protein (MCP)-1, and endotoxin. Significant decreases in the levels of TNF-alpha and IFN-gamma were observed in the LZD 2, 4, and 15 microg/ml groups as compared with that in the 0 microg/ml group (Dunnett's procedure; P < 0.05). The level of IL-10 tended to increase irrespective of the LZD concentration; however, no significant intergroup differences were observed [analysis of variance (ANOVA); P = 0.68]. No significant decrease of the endotoxin level was observed in the LZD 2, 4, or 15 microg/ml groups as compared with that in the 0 microg/ml group, with no significant intergroup differences (ANOVA; P = 0.83). No change in the MCP-1 levels was observed irrespective of the LZD concentration (ANOVA; P = 0.82). To conclude: (1) it appears possible that LZD inhibits the production of INF-gamma and TNF-alpha to a limited extent; (2) LZD did not exert any inhibitory effect on endotoxin production by bacteria, while suppressing cytokine production. The results indicate that LZD may have a significant role in saving the lives of patients with sepsis.
    Journal of Infection and Chemotherapy 04/2010; 16(2):94-9. · 1.55 Impact Factor
  • Nihon Shuchu Chiryo Igakukai zasshi 01/2009; 16(2):157-161.
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    Critical Care 01/2009; 13. · 4.93 Impact Factor