Faculty Profiles - NAKAO Atsunori

A case of traumatic abdominal wall hernia with delayed bowel obstruction

Intraperitoneally administered, hydrogen-rich physiologic solution protects against postoperative ileus and is associated with reduced nitric oxide production Reviewed

Ayana Okamoto, Keisuke Kohama, Michiko Aoyama-Ishikawa, Hayato Yamashita, Noritomo Fujisaki, Taihei Yamada, Tetsuya Yumoto, Nobuyuki Nosaka, Hiromichi Naito, Kohei Tsukahara, Atsuyoshi Iida, Keiji Sato, Joji Kotani, Atsunori Nakao

Surgery 160 ( 3 ) 623 - 631 2016.1

Soft tissue hematoma of the neck due to thyroid rupture with unusual mechanism Reviewed

Kohei Tsukahara, Keiji Sato, Tetsuya Yumoto, Atsuyoshi Iida, Nobuyuki Nosaka, Michihisa Terado, Hiromichi Naito, Yorihisa Orita, Tomoyuki Naito, Kentaro Miki, Mayu Sugihara, Satoko Nagao, Toyomu Ugawa, Atsunori Nakao

International Journal of Surgery Case Reports 26 217 - 220 2016.1

Takeshi Nishimura, Atsunori Nakao, Ayana Okamoto, Noritomo Fujisaki, Joji Kotani

Surgical Case Reports 1 ( 1 ) 2015.12

A case of traumatic abdominal wall hernia with delayed bowel obstruction. International journal

Takeshi Nishimura, Atsunori Nakao, Ayana Okamoto, Noritomo Fujisaki, Joji Kotani

Surgical case reports 1 ( 1 ) 15 - 15 2015.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Traumatic abdominal hernia is rare and difficult to diagnose from physical symptoms. PATIENT: A 60-year-old woman was admitted to the emergency department with complaints of vomiting after falling off a bicycle and hitting her abdomen against one of the handlebars 2 days earlier. Computed tomography (CT) demonstrated abdominal wall hernia from blunt trauma to the left upper abdomen. The patient underwent exploratory laparotomy, and the herniated bowel loop was not found to be perforated or gangrenous. Primary hernia repair without resection of the bowel loop was performed. RESULTS: Postoperative course was uneventful. CONCLUSION: Surgical exploration with primary repair of the defect is the definitive treatment in the present case, as the hernia contained an incarcerated loop of small bowel. The use of abdominal CT to confirm the diagnosis before operative repair of the hernia appears to be a safe and efficacious adjunct to physical examination.

DOI： 10.1186/s40792-015-0023-7

Hydrogen inhalation protects against acute lung injury induced by hemorrhagic shock and resuscitation Reviewed

Keisuke Kohama, Hayato Yamashita, Michiko Aoyama-Ishikawa, Toru Takahashi, Timothy R. Billiar, Takeshi Nishimura, Joji Kotani, Atsunori Nakao

SURGERY 158 ( 2 ) 399 - 407 2015.8

Language：English Publishing type：Research paper (scientific journal) Publisher：MOSBY-ELSEVIER

Introduction. Hemorrhagic shock followed by fluid resuscitation (HS/R) triggers an inflammatory response and causes pulmonary inflammation that can lead to acute lung injury (ALI). Hydrogen, a therapeutic gas, has potent cytoprotective, antiinflammatory, and antioxidant effects. This study examined the effects of inhaled hydrogen on ALI caused by HS/R.
Methods. Rats were subjected to hemorrhagic shock by withdrawing blood to lower blood pressure followed by resuscitation with shed blood and saline to restore blood pressure. After HS/R, the rats were maintained in a control gas of similar composition to room air or exposed to 1.3% hydrogen.
Results. HS/R induced ALL as demonstrated by significantly impaired gas exchange, congestion, edema, cellular infiltration, and hemorrhage in the lungs. Hydrogen inhalation mitigated lung injury after HS/R, as indicated by significantly improved gas exchange and reduced cellular infiltration and hemorrhage. Hydrogen inhalation did not affect hemodynamic status during HS/R Exposure to 1.3% hydrogen significantly attenuated the upregulation of the messenger RNAs for several proinflammatory mediators induced by HS/R Lipid peroxidation was reduced significantly in the presence of hydrogen, indicating antioxidant effects.
Conclusion. Hydrogen, administered through inhalation, may exert potent therapeutic effects against ALI induced by HS/R and attenuate the activation of inflammatory cascades.

DOI： 10.1016/j.surg.2015.03.038

Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia Reviewed

Taketo Inoue, Michiko Aoyama-Ishikawa, Shingo Kamoshida, Satoshi Nishino, Maki Sasano, Nobuki Oka, Hayato Yamashita, Motoki Kai, Atsunori Nakao, Joji Kotani, Makoto Usami

REPRODUCTION 150 ( 2 ) 105 - 114 2015.8

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOSCIENTIFICA LTD

Orchitis (testicular swelling) often occurs during systemic inflammatory conditions, such as sepsis. Interleukin 18 (IL18) is a proinflammatory cytokine and is an apoptotic mediator during endotoxemia, but the role of IL18 in response to inflammation in the testes was unclear. WT and IL18 knockout (KO) mice were injected lipopolysaccharide (LPS) to induce endotoxemia and examined 12 and 48 h after LPS administration to model the acute and recovery phases of endotoxemia. Caspase activation was assessed using immunohistochemistry. Protein and mRNA expression were examined by western blot and quantitative real-time RT-PCR respectively. During the acute phase of endotoxemia, apoptosis (as indicated by caspase-3 cleavage) was increased in WT mice but not in IL18 KO mice. The death receptor-mediated and mitochondrial-mediated apoptotic pathways were both activated in the WT mice but not in the KO mice. During the recovery phase of endotoxemia, apoptosis was observed in the IL18 KO mice but not in the WT mice. Activation of the death-receptor mediated apoptotic pathway could be seen in the IL18 KO mice but not the WT mice. These results suggested that endogenous IL18 induces germ cell apoptosis via death receptor mediated- and mitochondrial-mediated pathways during the acute phase of endotoxemia and suppresses germ cell apoptosis via death-receptor mediated pathways during recovery from endotoxemia. Taken together, IL18 could be a new therapeutic target to prevent orchitis during endotoxemia.

DOI： 10.1530/REP-14-0427

A Case of Perianal Impalement Rectal Injury Presenting Pneumoperitoneum

39 ( 2 ) 132 - 134 2015.2

Endogenous Interleukin 18 Suppresses Hyperglycemia and Hyperinsulinemia during the Acute Phase of Endotoxemia in Mice Reviewed

Hayato Yamashita, Michiko Aoyama-Ishikawa, Miki Takahara, Chisato Yamauchi, Taketo Inoue, Makoto Miyoshi, Noriaki Maeshige, Makoto Usami, Atsunori Nakao, Joji Kotani

SURGICAL INFECTIONS 16 ( 1 ) 90 - 96 2015.2

Language：English Publishing type：Research paper (scientific journal) Publisher：MARY ANN LIEBERT, INC

Background: Hyperglycemia associated with insulin resistance is common among critically ill patients. Interleukin (IL)-18 has been linked with hyperglycemia and insulin resistance in chronic disease, but the relation between IL-18 and insulin resistance during critical illness was unexplored. This study investigated whether IL-18 modulates hyperglycemia and insulin resistance during acute inflammation.
Methods: We injected lipopolysaccharide (LPS) 40 mg/kg into wild-type (WT) and IL-18 knockout (KO) mice to induce endotoxemia and examined insulin resistance and insulin-dependent signaling pathways during the acute phase.
Results: During the first hour after LPS treatment, IL-18 KO mice showed higher blood glucose and insulin and less insulin receptor substrate-1 and less phosphorylated Akt in the liver compared with WT mice. Interleukin-18 KO mice exhibited better survival after LPS treatment.
Conclusions: The findings suggest that endogenous IL-18 may attenuate hyperglycemia and modulate insulin signaling in liver. Accordingly, IL-18 may modulate glucose tolerance during acute inflammation.

DOI： 10.1089/sur.2013.269

A Case of Traumatic Carotid Cavernous Fistula after the Head Injury Which Healed Spontaneously

39 ( 1 ) 62 - 64 2015.1

High Frequency Oscillatory Ventilation(HFOV)が奏功したインフルエンザ重症呼吸不全の1症例

藤崎宣友, 岡本彩那, 満保直美, 寺嶋真理子, 中尾篤典, 小谷穣治

日本集中治療医学会雑誌 22 ( Suppl. ) [DP109 - 2] 2015.1

To remove or not remove? Twenty or more sewing needles in the gastrointestinal tract

Yoshimichi Yamaguchi, Mariko Terashima, Atsunori Nakao, Norichika Yoshie, Noritomo Fujisaki, Taihei Yamada, Ayana Okamoto, Atsunori Hashimoto, Joji Kotani

Acute Medicine & Surgery 1 ( 4 ) 250 - 251 2014.10

Successful treatment of panton-valentine leukocidin-expressing staphylococcus aureus-Associated pneumonia co-infected with influenza using extracorporeal membrane oxygenation

Noritomo Fujisaki, Azusa Takahashi, Takahiro Arima, Tomoya Mizushima, Katsuki Ikeda, Hiroyuki Kakuchi, Atsunori Nakao, Joji Kotani, Koji Sakaida

In Vivo 28 ( 5 ) 961 - 966 2014.9

Language：English Publishing type：Research paper (scientific journal) Publisher：International Institute of Anticancer Research

Background: Panton-Valentine leukocidin (PVL) is a cytotoxin that causes leukocyte destruction and lung necrosis. Managing respiratory failure and acute respiratory distress syndrome secondary to PVL-expressing Staphylococcus aureus pneumonia and its associated lung necrosis with mechanical ventilation is challenging. We report a patient with lifethreatening PVL-expressing S. aureus-Associated pneumonia who was rescued using extracorporeal membrane oxygenation (ECMO). Case Report: We examined the case of a woman who presented to our Emergency Department with septic shock due to PVL-expressing S. aureus-Associated pneumonia. A 27-yearold Filipino woman was transferred to our hospital due to severe dyspnea, hemosputum, and high-grade fever. She had a medical history of osteosarcoma of the leg and hyperthyroidism. On arrival, her vital signs indicated septic shock, with a white blood cell count of 3.5×103/μl. Because a Gram stain of her sputum indicated SA, therapy with antibiotics, including meropenem and vancomycin, was started. Hypoxemia necessitated intubation and ventilation. Because the patient's PaO2/FiO2 remained less than 60 mmHg and her blood pressure was unstable despite aggressive conventional management, venoarterial ECMO was administered approximately 11 h after her arrival. The ECMO circuit was changed to veno-venous ECMO on day 7 and the patient was successfully weaned off ECMO after 12 days of treatment. She was discharged from the hospital 104 days after admission. Conclusion: This case demonstrates that early induction of ECMO support can be a reasonable therapeutic option for PVL-S. aureus-Associated pneumonia. This patient's successful outcome might be attributable to early establishment of ECMO to prevent ventilation-induced lung injury.

Scopus

Application of carbon monoxide for treatment of acute kidney injury

頭部外傷後に内頸動脈海綿静脈洞瘻を来し自然治癒した1症例

岡本彩那, 坂田寛之, 松田健一, 満保直美, 西村健, 藤崎宣友, 山田太平, 寺嶋真理子, 中尾篤典, 久保山一敏, 小谷穣治

日本救急医学会雑誌 25 ( 8 ) 543 - 543 2014.8

Atsunori Nakao, Taihei Yamada, Keisuke Kohama, Norichika Yoshie, Noritomo Fujisaki, Joji Kotani

Acute Medicine & Surgery 1 ( 3 ) 127 - 134 2014.7

Flail Chestの治療経験観血的整復固定術と陽圧換気管理

山田太平, 坂田寛之, 尾迫貴章, 寺嶋真理子, 宮脇淳志, 中尾篤典, 小谷穣治

日本外傷学会雑誌 28 ( 2 ) 225 - 225 2014.5

IL18 Production and IL18 Promoter Polymorphisms Correlate with Mortality in ICU Patients Reviewed

Taihei Yamada, Michiko Aoyama-Ishikawa, Hayato Yamashita, Mayu Fujiwara, Makoto Usami, Takahiro Ueda, Mariko Terashima, Keisuke Kohama, Atsunori Nakao, Joji Kotani

IN VIVO 28 ( 3 ) 391 - 396 2014.5

Language：English Publishing type：Research paper (scientific journal) Publisher：INT INST ANTICANCER RESEARCH

Background: Single nucleotide polymorphisms in the promoter of interleukin (IL)-18 (-607C/A and -137G/C) may affect the clinical course of inflammatory diseases. This study examined the relationship between the plasma IL18 levels, IL18 promoter polymorphism, and outcomes in the intensive care unit (ICU) setting. Patients and Methods: Plasma IL18 levels, IL18 promoter genotype, clinical variables, including APACHE II score, and mortality were examined in 70 ICU patients. Results: Plasma IL18 levels were significantly higher in patients who did not survive the ICU stay than in patients who survived, and were correlated with APACHE II score. When examined by IL18 promoter genotype, only patients with the -607CA genotype exhibited differences in IL18 expression between survivors and non-survivors. Conclusion: Plasma IL18 levels may predict outcome in patients with sepsis. IL18 promoter polymorphism, especially at -607, may increase IL18 production in some patients and might be useful in predicting the outcome of patients with sepsis in the ICU.

Supplementation of parenteral nutrition with fish oil attenuates acute lung injury in a rat model Reviewed

Keisuke Kohama, Atsunori Nakao, Mariko Terashima, Michiko Aoyama-Ishikawa, Takayuki Shimizu, Daisuke Harada, Mitsuo Nakayama, Hayato Yamashita, Mayu Fujiwara, Joji Kotani

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 54 ( 2 ) 116 - 121 2014.3

Language：English Publishing type：Research paper (scientific journal) Publisher：JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION

Fish oil rich in n-3 polyunsaturated fatty acids has diverse immunomodulatory properties and attenuates acute lung injury when administered in enternal nutrition. However, enteral nutrition is not always feasible. Therefore, we investigated the ability of parenteral nutrition supplemented with fish oil to ameliorate acute lung injury. Rats were infused with parenteral nutrition solutions (without lipids, with soybean oil, or with soybean oil and fish oil) for three days. Lipopolysaccharide (15 mg/kg) was then administered intratracheally to induce acute lung injury, characterized by impaired lung function, polymorphonuclear leukocyte recruitment, parenchymal tissue damage, and upregulation of mRNAs for inflammatory mediators. Administration of parenteral nutrition supplemented with fish oil prior to lung insult improved gas exchange and inhibited neutrophil recruitment and upregulation of mRNAs for inflammatory mediators. Parenteral nutrition supplemented with fish oil also prolonged survival. To investigate the underlying mechanisms, leukotriene B4 and B5 leukotriene secretion was measured in neutrophils from the peritoneal cavity. The neutrophils from rats treated with fish oil-rich parenteral nutrition released significantly more leukotriene B5, an anti-inflammatory eicosanoid, than neutrophils isolated from rats given standard parenteral nutrition. Parenteral nutrition with fish oil significantly reduced lipopolysaccharide-induced lung injury in rats in part by promoting the synthesis of anti-inflammatory eicosanoids.

DOI： 10.3164/jcbn.13-90

A simple scoring system based on neutrophil count in sepsis patients Reviewed

Takahiro Ueda, Michiko Aoyama-Ishikawa, Atsunori Nakao, Taihei Yamada, Makoto Usami, Joji Kotani

MEDICAL HYPOTHESES 82 ( 3 ) 382 - 386 2014.3

Language：English Publishing type：Research paper (scientific journal) Publisher：CHURCHILL LIVINGSTONE

Background: The assessment of critically ill patients is often a challenge for clinicians. There are a number of scoring systems such as Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) and C-reactive protein test (CRP), which have been shown to correlate with outcome in a variety of Intensive Care Unit (ICU) patients. Therefore, use of repeated measures of these preexisting scores over time is a reasonable attempt to assess the severity of organ dysfunction and predict outcome in critically ill patients. Several reports suggest that the neutrophil is a useful marker of sepsis. However, since both a large number and a small number of neutrophils indicate a severe situation, neutrophil count is difficult to use to directly predict patients'.
The hypothesis: We proposed a novel scoring system identify predictive factors using a simple blood cell count that may be associated with mortality in ICU patients. Our novel scoring system (n-score) was calculated as follows: ranges of neutrophils of 0-4999 cells/mm(3) and 5000-9999 cells/mm(3) were defined as 3 and 1 points, respectively. When the neutrophil count was over 10,000 cells/mm(3), the score was calculated by dividing the number of cells by 10,000. Then, 1 or 2 points were added when patients were female or male, respectively. We hypothesize that n-score may be a simple and easy scoring system to estimate mortality of the patients with sepsis and severe sepsis/septic shock without requirement of special methods or special measuring equipment, and may be as reliable as the APACHE II score or SOFA score.
Evaluation of the hypothesis: The retrospective evaluation was conducted at the Department of Emergency, Disaster and Critical Care Medicine at the Hyogo College of Medicine. Seventy-seven patients who were admitted to the emergency center and diagnosed sepsis or severe sepsis/septic shock between June 2007 and December 2012 and gave informed consent were enrolled. The n-score was significantly higher in non-survivors of sepsis and severe sepsis/septic shock (p < 0.01, t-test) than in survivors. The ROC curve showed a sensitivity of 61.5% and a specificity of 80.4% at an n-score of 3.8 points; the area under the curve was 0.736. In addition, n-score correlated with APACHE II score (p < 0.01, R = 0.378) and SOFA score (p < 0.05, R = 0.256) on admission.
Conclusion: Based on these preliminary evaluations, we hypothesize that n-score may be a useful scoring system to detect risk of death in sepsis and severe sepsis/septic shock. (C) 2014 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.mehy.2014.01.007

Recipient hyperbilirubinaemia protects cardiac graft in rat heterotopic heart transplantation Reviewed

Sungsoo Lee, Taihei Yamada, Takaaki Osako, Donna B. Stolz, Masanori Abe, Kenneth R. McCurry, Noriko Murase, Joji Kotani, Atsunori Nakao

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 45 ( 3 ) 481 - 488 2014.3

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS INC

OBJECTIVES: Since bilirubin is a known powerful antioxidant, this study examined whether recipient hyperbilirubinaemia protected heart grafts from ischaemia/reperfusion (I/R) injury and chronic rejection associated with rat cardiac transplantation.
METHODS: Heterotopic heart transplantation (HTx) was performed using congenitally hyperbilirubinaemic GUNN (j/j) and normobilirubinaemic GUNN (+/+) rats. Syngenic grafts from +/+ rats were transplanted into +/+ or j/j rats with 6 or 18 h cold storage in University of Wisconsin solution to study I/R injury. To evaluate the effect on chronic rejection, Brown Norway rat heart grafts were transplanted into +/+ or j/j rats under short-course tacrolimus immunosuppression.
RESULTS: The +/+ grafts in j/j rats demonstrated significantly lower serum creatine phosphokinase and higher left ventricular developed pressures and had smaller infarct areas than +/+ rats at 3 h after reperfusion. Graft survival with 18 h cold storage increased from 0% in +/+ rats to 41.7% in j/j rats. Malondialdehyde (a marker of lipid peroxidation), mRNA of the inflammatory mediators and phosphorylation of ERK1/2 were significantly decreased in the grafts transplanted into j/j rats compared with those transplanted into +/+ rats 1-3 h after reperfusion. The mean allograft survival in j/j recipients was prolonged to a median survival of 150 days from 84 days in +/+ recipients and was associated with less macrophage infiltrates and less intragraft inflammatory cytokine mRNA at d60. In vitro T-cell proliferation was significantly inhibited in the presence of bilirubin.
CONCLUSIONS: Recipient hyperbilirubinaemia ameliorated cardiac I/R injury, as well as chronic allograft rejection following HTx via regulation of inflammatory responses or T-cell proliferation.

DOI： 10.1093/ejcts/ezt402