Publications by authors named "Tetsuya Kitagawa"

63 Publications

A rare case of invasive thymoma presented a dramatic response to low-dose prednisolone as a single-drug therapy.

J Med Invest 2021 ;68(3.4):396-399

Department of Cardiovascular Surgery, Shikoku Central Hospital of the Mutual aid Association of Public School teachers, Shikoku-Chuo, Japan.

A 76-year-old woman with a history of angina pectoris, hypertension and dyslipidemia was pointed out an abnormal opacity in the right hilar region on routine chest X-ray. Chest computed tomography showed masses in the anterior mediastinum with the invasion of the adjacent ascending aorta, right brachiocephalic vein and right pleura. Histologic examination led to a diagnosis of Masaoka stage IVa thymoma. Three courses of chemotherapy were given, but further tumor progression was seen. Thereafter, the patient was followed without aggressive treatments. One year after the initial diagnosis, she presented with dyspnea and right chest pain. Chest CT revealed right massive pleural effusion with pleural dissemination and much further progression of existing tumors. For the purpose of symptom palliation, a low dose (5 mg / day) of prednisolone was commenced, which unexpectedly led to marked alleviation of patient's symptoms and dramatic decrease of pleural effusion. To the best of our knowledge, this is the first report of an invasive thymoma responded to low-dose corticosteroid. The present case suggests that corticosteroids, even at low doses, might be potentially effective for invasive thymoma after failure of surgery, chemotherapy and radiotherapy. J. Med. Invest. 68 : 396-399, August, 2021.
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http://dx.doi.org/10.2152/jmi.68.396DOI Listing
November 2021

A case of chest tightness variant asthma : the usefulness of fractional exhaled nitric oxide as a marker for the diagnosis and clinical improvement.

J Med Invest 2021 ;68(3.4):389-392

Department of Cardiovascular Surgery, Shikoku Central Hospital of the Mutual aid Association of Public School teachers, Shikoku-Chuo, Japan.

A 50-year-old woman was referred to our hospital for further examination of severe constricting pain at the right-side dominant anterior chest. She had medical history of outgrown childhood asthma and allergies to several animals. Chest auscultation revealed no wheezes, rhonchi and other crackles. Laboratory findings showed an eosinophilia and an elevation of total immunoglobulin E. The results of an electrocardiogram, a chest X-ray and a chest CT were unremarkable. A fractional exhaled nitric oxide value remarkably elevated, but the abnormalities in pulmonary function test were modest. Her chest pain was ameliorated after inhaling procaterol. Based on these findings, a diagnosis of chest tightness variant asthma was formulated, and we started treatment with inhaled corticosteroid / long acting β2 agonist. At two-weeks after treatment, her symptom markedly improved and a fractional exhaled nitric oxide value decreased, which led to a definitive diagnosis of chest tightness variant asthma. A fractional exhaled nitric oxide value further decreased to the normal range in consistent with symptom disappearance at 10-months after treatment, indicating the usefulness of fractional exhaled nitric oxide as a promising marker for the diagnosis and clinical improvement of chest tightness variant asthma. J. Med. Invest. 68 : 389-392, August, 2021.
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http://dx.doi.org/10.2152/jmi.68.389DOI Listing
November 2021

The clinical usefulness of a new hand-held device for fractional exhaled nitric oxide measurement, NIOX VERO®, for diagnosing the etiology of cough.

J Med Invest 2020 ;67(3.4):265-270

Department of Cardiovascular Surgery, Shikoku Central Hospital of the Mutual aid Association of Public School teachers, 2233 Kawanoe-cho, Shikoku-Chuo, 799-0193, Japan.

Cough is one of the most common symptoms seen in clinical practice, however the differential diagnosis is often difficult. The utility of fractional exhaled nitric oxide (FeNO) measurement in the differential diagnosis of the etiology of cough has been reported. NIOX VERO® (NOV) is a new hand-held device that will replace NIOX MINO®, but its diagnostic utility has not been fully elucidated in clinical practice. In this study, the performance of NOV for FeNO measurements was determined. We retrospectively analyzed 243 consecutive patients complaining cough. Among 243 patients, final diagnosis was cough variant asthma (CVA) in 74 (30.5%), bronchial asthma (BA) in 48 (19.8%), post-infectious cough (PIC) in 52 (21.4%), atopic chough (AC) in 24 (9.9%), gastroesophageal reflux disease (GERD) in 10 (4.1%), and Others in 35 (14.4%). FeNO values were significantly higher in CVA and BA as compared to PIC, AC, GERD, and Others. In the multivariate analysis, only FeNO value was identified as independent factors to discriminate CVA and non-CVA other than BA. These findings indicated that FeNO measured by using NOV could be used as a diagnostic marker of intractable cough, especially for the differential diagnosis of CVA from non-CVA. J. Med. Invest. 67 : 265-270, August, 2020.
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http://dx.doi.org/10.2152/jmi.67.265DOI Listing
October 2021

Pathophysiology and Complications during Extracorporeal Circulation.

J Med Invest 2020;67(3.4):229-235

Department of Dental Anesthesiology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

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http://dx.doi.org/10.2152/jmi.67.229DOI Listing
October 2021

Correction to: Novel quantitative and objective structured assessment of technical skill for slip knotting.

Gen Thorac Cardiovasc Surg 2020 Mar;68(3):310

The committee of The Japanese Society for Cardiovascular Surgery Under-Forty, 2-26-9, Hongou, Bunkyo-ku, Tokyo, 113-0033, Japan.

The article "Novel quantitative and objective structured assessment of technical skill for slip knotting", written by.
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http://dx.doi.org/10.1007/s11748-019-01246-9DOI Listing
March 2020

Appropriate Surgical Treatment of Symptomatic Primary Varicose Veins Decreases Systemic Inflammatory Biomarkers.

Ann Vasc Dis 2019 Sep;12(3):367-371

Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Tokushima, Japan.

: To evaluate the relationship between systemic inflammatory biomarkers and efficacy of surgical treatment of primary varicose veins of the lower extremities. : Total 12 patients who underwent endovenous laser ablation or stripping of varicose veins and six healthy subjects were enrolled. Structural and molecular changes of varices were assessed by immunohistochemical staining with anti-monocyte chemotactic protein-1 (MCP-1). MCP-1 and interleukin-6 (IL-6) levels in systemic antecubital blood were measured before and at 12 weeks after treatment. : Immunohistochemical staining revealed prominent manifestation of MCP-1-positive endothelial cells in the walls of varices. Preoperative serum MCP-1 and IL-6 levels in the patients were significantly higher than those in the control (166±12 pg/mL vs 99±10 pg/mL, p=0.003; 5.1±0.95 pg/mL vs 0.0±0.0 pg/mL, p=0.001, respectively). The values were significantly correlated with the severity of chronic venous insufficiency (CVI). Postoperative serum MCP-1 level significantly decreased compared with the preoperative level (152±10 pg/mL vs 166±12 pg/mL, p=0.048). The values after endovenous laser ablation did not significantly decrease compared with those after stripping. : Varicose veins with CVI increase inflammatory biomarker levels in the local tissue and systemic blood. Appropriate treatment of symptomatic varicose veins decreases inflammatory biomarker levels.
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http://dx.doi.org/10.3400/avd.oa.19-00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766771PMC
September 2019

Novel quantitative and objective structured assessment of technical skill for slip knotting.

Gen Thorac Cardiovasc Surg 2020 Jun 15;68(6):557-564. Epub 2019 Oct 15.

The committee of The Japanese Society for Cardiovascular Surgery Under-Forty, 2-26-9, Hongou, Bunkyo-ku, Tokyo, 113-0033, Japan.

Objective: Currently, no quantitative and objective method has been established for evaluating competencies in basic surgical techniques. The aim of this study was to develop a structured assessment tool for slip knotting and verify how well current board certification system discriminates the level of basic surgical skill.

Methods: We examined 171 cardiovascular surgical fellows using a novel assessment method for slip knotting that was developed by the committee of the Under-Forty of the Japanese Society of Cardiovascular Surgery. We compared the scores and examinees' surgical experience for validation. We analyzed the relationship between board certification and the scores.

Results: The scores differentiated the general surgical board-certified surgeons from those without certification. Surgical experiences such as training years and number of operated cases and scores were correlated. Among the board-certified surgeons, the group with daily off-the-job training, or simulator-based skill training had a significantly higher mean score (67.4 ± 3.0 vs 55.4 ± 3.1, p = 0.008) and lower rate of poor scorers (7.1% vs 38.5%, p = 0.004). A multivariate analysis revealed that board certification did not predict high scores. Daily off-the-job training was the only independent predictor of high scores (odds ratio: 2.41, 95% confidence interval: 0.01-1.20, p = 0.014).

Conclusions: This novel quantitative and objective assessment tool for technical skill in slip knotting was found to be valid to examine the skill for slip knotting. In this study, current board certification discriminated the level of basic surgical skill. However, it could not distinguish extremely low scorers perfectly. Some board-certified surgeons showed poor technical competency, especially those without off-the-job training.
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http://dx.doi.org/10.1007/s11748-019-01222-3DOI Listing
June 2020

Accuracy and reliability of continuous blood glucose monitoring during pediatric cardiopulmonary bypass.

J Artif Organs 2019 Dec 24;22(4):353-356. Epub 2019 Jun 24.

Department of Dental Anesthesiology, Tokushima University Hospital, Tokushima, Japan.

The purpose of this study was to assess the accuracy and reliability of a continuous blood glucose monitoring system (artificial endocrine pancreas; STG-55, Nikkiso, Tokyo, Japan) during pediatric cardiopulmonary bypass surgery. Twenty-five pediatric patients scheduled to undergo cardiovascular surgery with cardiopulmonary bypass (age 4 months to 11 years; body weight 5.6-59.7 kg) were enrolled. The glucose sensor line of the artificial endocrine pancreas was connected to the venous side of the cardiopulmonary bypass circuit and used for continuous blood glucose monitoring. We obtained 192 samples for blood gas assessment from the cardiopulmonary bypass circuit, and i-STAT (Abbott, East Windsor, NJ, USA) was used for conventional blood glucose assessment. The accuracies of continuous glucose measurements (STG-55) and conventional intermittent glucose measurements (i-STAT) during cardiopulmonary bypass were compared by means of Clarke error grid analysis. The results were divided into five zones, A, B, C, D, and E, and 78.6% of paired measurements were in zone A, while 21.4% were in zone B. We confirmed that the results of this continuous blood glucose monitoring system for cardiopulmonary bypass during pediatric cardiovascular surgery were highly reliable. An artificial endocrine pancreas may facilitate the safe use of intensive insulin therapy during pediatric cardiovascular surgery.
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http://dx.doi.org/10.1007/s10047-019-01111-9DOI Listing
December 2019

Inhibition of Atherosclerotic Plaque Development by Oral Administration of α-Glucosyl Hesperidin and Water-Dispersible Hesperetin in Apolipoprotein E Knockout Mice.

J Am Coll Nutr 2019 01 15;38(1):15-22. Epub 2018 Oct 15.

a Department of Cardiovascular Surgery , Tokushima University Graduate School/Institute of Biomedical Sciences , Tokushima , Japan.

Objective: Hesperidin, an abundant flavonoid in citrus fruit, and its aglycone, hesperetin, have been reported to possess various physiological activities, including antioxidant, anti-inflammatory, hypolipidemic, and antihypertensive activities. In this study, we investigated whether α-glucosyl hesperidin and water-dispersible hesperetin have protective effects on atherosclerotic progression in apolipoprotein E knockout (Apo-E KO) mice.

Methods: Ten-week-old male Apo-E KO mice were randomly assigned a regular high-fat diet, a high-fat diet with 0.5% α-glucosyl hesperidin, or a high-fat diet with 0.1% water-dispersible hesperetin for 12 weeks. Measurement of plasma total cholesterol levels, histological staining of aortic root, and immunohistochemistry for macrophages were performed to evaluate atherosclerotic plaque formation. Vascular reactivity of mouse aortic rings was also measured.

Results: Both α-glucosyl hesperidin and water-dispersible hesperetin reduced plasma total cholesterol level. They also reduced plaque formation area, adipose deposition, and macrophage infiltration into atherosclerotic lesion. Vascular-endothelium-dependent relaxation in response to acetylcholine was improved in both experimental diet groups compared to the high-fat diet group.

Conclusions: Our study suggests that both α-glucosyl hesperidin and water-dispersible hesperetin exert protective effects on atherosclerotic progression in Apo-E KO mice because they exhibit hypolipidemic activity, reduce inflammation through macrophages, and prevent endothelial dysfunction.
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http://dx.doi.org/10.1080/07315724.2018.1468831DOI Listing
January 2019

The ratio of contrast medium volume to estimated glomerular filtration rate as a predictor of contrast-induced nephropathy after endovascular aortic repair.

J Med Invest 2018 ;65(1.2):116-121

Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School.

Objective: This study aimed to determine the perioperative predictors of contrast medium-induced nephropathy (CIN) after endovascular aortic repair (EVAR).

Materials And Methods: The data of 203 consecutive patients who underwent elective EVAR for thoracic and abdominal aortic aneurysm between January 2014 and September 2014 were retrospectively analyzed. CIN was defined according to the diagnostic criteria of the European Society of Urogenital Radiology.

Results: Fourteen patients (6.9%) developed CIN after EVAR. Contrast medium volume (CV), preoperative serum creatinine, estimated glomerular filtration rate (eGFR), and the CV/eGFR ratio were significantly related with CIN development after EVAR. The CV/eGFR ratio was significantly higher in patients with CIN than those without CIN. Receiver operator characteristic curve analysis showed that the area under the curve of the CV/eGFR ratio was 0.782, indicating that it was the most important predictor. The appropriate CV/eGFR ratio cutoff was 1.62. Sensitivity and specificity were 85.7% and 65.6%, respectively.

Conclusions: The CV/eGFR ratio was a useful predictor of contrast medium-induced nephropathy after EVAR. It is possible that the score can be used in patients when managing the EVAR techniques and contrast medium volume. J. Med. Invest. 65:116-121, February, 2018.
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http://dx.doi.org/10.2152/jmi.65.116DOI Listing
September 2018

Pseudoaneurysm of the Anterior Tibial Artery following Ankle Arthroscopy in a Soccer Player.

Case Rep Orthop 2017 18;2017:2865971. Epub 2017 May 18.

Department of Orthopedics, Institute of Biomedical Science, Tokushima University Graduate School, Tokushima, Japan.

Ankle arthroscopy carries a lower risk of vascular complications when standard anterolateral and anteromedial portals are used. However, the thickness of the fat pad at the anterior ankle affords little protection for the thin-walled anterior tibial artery, rendering it susceptible to indirect damage during procedures performed on the anterior ankle joint. To our knowledge, only 11 cases of pseudoaneurysm involving the anterior tibial artery after ankle arthroscopy have been described in the literature. Here we reported a rare case of a 19-year-old soccer player who presented with pseudoaneurysm of the anterior tibial artery following ankle arthroscopy using an ankle distraction method and underwent anastomosis for the anterior tibial artery injury. Excessive distraction of the ankle puts the neurovascular structures at greater risk for iatrogenic injury of the anterior tibial artery during ankle arthroscopy. Surgeons should look carefully for postoperative ankle swelling and pain after ankle arthroscopy.
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http://dx.doi.org/10.1155/2017/2865971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451781PMC
May 2017

Effects of Transplanted Human Cord Blood-Mononuclear Cells on Pulmonary Hypertension in Immunodeficient Mice and Their Distribution.

J Med Invest 2017 ;64(1.2):43-49

Department of Cardiovascular Surgery, Graduate School of Biomedical Sciences, Tokushima University.

Objectives: To investigate the effects of human umbilical cord blood-derived mononuclear cell (hUCB-MNC) transplantation on pulmonary hypertension (PH) induced by monocrotaline (MCT) in immunodeficient mice and their distribution.

Methods: MCT was administered to BALB/c Slc-nu/nu mice, and PH was induced in mice 4 weeks later. Fresh hUCB-MNCs harvested from a human donor after her delivery were injected intravenously into those PH mice. The medial thickness of pulmonary arterioles, ratio of right ventricular to septum plus left ventricular weight (RV/S+LV), and ratio of acceleration time to ejection time of pulmonary blood flow waveform (AT/ET) were determined 4 weeks after hUCB-MNC transplantation. To reveal the incorporation into the lung, CMTMR-labeled hUCB-MNCs were observed in the lung by fluorescent microscopy. DiR-labeled hUCB-MNCs were detected in the lung and other organs by bioluminescence images.

Results: Medial thickness, RV/S+LV and AT/ET were significantly improved 4 weeks after hUCB-MNC transplantation compared with those in mice without hUCB-MNC transplantation. CMTMR-positive hUCB-MNCs were observed in the lung 3 hours after transplantation. Bioluminescence signals were detected more strongly in the lung than in other organs for 24 hours after transplantation.

Conclusions: The results indicate that hUCB-MNCs are incorporated into the lung early after hUCB-MNC transplantation and improve MCT-induced PH. J. Med. Invest. 64: 43-49, February, 2017.
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http://dx.doi.org/10.2152/jmi.64.43DOI Listing
October 2017

Long-term Results After Open Mitral Commissurotomy for a One-Month-Old Infant With Mitral Stenosis.

J Med Invest 2017 ;64(1.2):187-191

Department of Cardiovascular Surgery, Graduate School of Biomedical Sciences, Tokushima University.

The strategy for an infant with congenital mitral stenosis should be determined by three important factors: left ventricular volume, the degree of the systemic outflow tract obstruction, and the type of mitral valve dysfunction. A successful staged biventricular repair in early infancy for a patient who had congenital mitral stenosis with short chordae, hypoplastic left ventricle and coarctation of the aorta, and the long-term results are described. There were the following important hemodynamic factors that led to the successful biventricular repair in the patient. Total systemic output was barely supplied through the hypoplastic left ventricle after closure of the ductus arteriosus on admission. The neonate underwent repair of coarctation of the aorta alone as the initial stage at 9 days after birth. Also, spontaneous closure of the foramen ovale following repair of coarctation of the aorta accelerated the progressive left ventricular growth. Open mitral commissurotomy with an interatrial fenestration using the modified Brawley's approach was performed for a 40-day-old infant. Good left ventricular growth and good mitral valve function have been observed for 18 years after open mitral commissurotomy. Appropriate early augmentation of left ventricular inflow through the mitral valve might be effective for growth of a hypoplastic left ventricle. J. Med. Invest. 64: 187-191, February, 2017.
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http://dx.doi.org/10.2152/jmi.64.187DOI Listing
October 2017

The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe.

J Nutr Biochem 2016 09 31;35:66-73. Epub 2016 May 31.

Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD+Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD+E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4β-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4β-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4β-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function.
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http://dx.doi.org/10.1016/j.jnutbio.2016.05.010DOI Listing
September 2016

Efficacy and Optimal Timing of Endovascular Treatment for Type B Aortic Dissection.

Ann Vasc Dis 2015 25;8(4):307-13. Epub 2015 Nov 25.

Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

Objectives: To determine the efficacy and the optimal timing of thoracic endovascular aortic repair (TEVAR) for closing the primary entry in uncomplicated patients with chronic type B aortic dissection and a patent false lumen (FL).

Methods: Thirteen patients underwent TEVAR for aortic dissection between 2008 and 2012. These patients had chronic dissection with a patent FL and expansion of the aorta. Early TEVAR was performed for five patients within 1-7 months from the index dissection (TEVAR-EC group) and delayed TEVAR was performed for eight patients within 1-16 years (TEVAR-DC group). Changes in the diameters and volumes of the true lumen (TL) and FL and the aortic remodeling were assessed by multidetector computed tomography for 3 years after TEVAR.

Results: The reduction rate of FL in the thoracic aorta was notably higher in the TEVAR-EC group than in the TEVAR-DC group regardless of the presence or absence of distal retrograde flow. There was a significant TL expansion despite different timings of TEVAR.

Conclusions: Early TEVAR resulted in good prognosis and preferable aortic remodeling in uncomplicated patients with chronic type B aortic dissection and a patent FL, and we recommend early TEVAR within seven months after the index dissection.
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http://dx.doi.org/10.3400/avd.oa.15-00069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691505PMC
January 2016

PPAR-γ agonist attenuates inflammation in aortic aneurysm patients.

Gen Thorac Cardiovasc Surg 2015 Oct 27;63(10):565-71. Epub 2015 Jul 27.

Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.

Background And Objective: Peroxisome proliferator-activated receptor (PPAR) -γ agonist, which is an anti-diabetes drug and reduces expression of tumor necrosis factor (TNF)-α, reported to have the effects for anti-inflammation in our body. In cardiovascular fields, this PPAR-γ agonist already reported to suppress progression of coronary atherosclerosis. Various cytokines, which is secreted from fat tissues around artery, promote atherosclerosis and/or aneurysmal changes in aorta/artery. Objective of our study is to clarify whether PPAR-γ agonist has anti-inflammatory effects in aorta of patients with aortic aneurysm (AA).

Patients And Methods: The medical ethics committee in Tokushima University Hospital approved protocol for this study. Sixteen patients with AA (more than 5 cm in diameter, scheduled open surgery) were divided into two groups; one is PPAR-γ agonist administrating group [Formula: see text] n = 6, group P[Formula: see text], and another is the without group [Formula: see text] n = 10, group C[Formula: see text]. PPAR-γ agonist, whose dose was 15 mg/day, was administrated in the group P for more than 2 months before aneurysectomy and grafting (mean; 4.2 ± 3.4 months) (Supplemental Table 1). Biopsy specimens were obtained from abdominal subcutaneous fat, greater omentum, retroperitoneal periaortic fat and aneurysmal wall in surgical procedure. Blood examination also achieved before/after procedure. Harvested specimens were analyzed with histology (HE and EVG), immunohistochemistry (macrophage) and RT-PCR (adiponectin, MCP-1, TNF-α, CD68, matrix metalloprotease (MMP)-2, MMP-9).

Results: Macrophage infiltration in aortic wall and retroperitoneal periaortic fat among group P was significantly decreased compared to that among group C. Adiponectin expressions in both subcutaneous fat and retroperitoneal periaortic fat among the group P (adiponectin/β-actin) were significantly increased compared to those among the group C [subcutaneous fat; 16.8 ± 13.9 vs. 5.82 ± 2.94 (P = 0.04), retroperitoneal periaortic fat; 21.3 ± 24.1 vs. 2.12 ± 1.69 (P = 0.04)]. On the other hand, expressions of TNF-α, and MMP-9 in both aortic aneurysmal wall and retroperitoneal periaortic fat among group P were significantly decreased. [(Aortic aneurysmal wall; TNF-α; 0.45 ± 0.15 vs. 5.18 ± 3.49 (P = 0.02), MMP-9; 39.6 ± 69.0 vs. 721 ± 741 (P = 0.04)], [retroperitoneal periaortic fat; TNF-α; 1.14 ± 0.36 vs. 26.4 ± 25.0 (P = 0.048), MMP-9; 0.18 ± 0.21 vs. 50.0 ± 41.8 (P = 0.047)].

Conclusion: These data may indicate that PPAR-γ agonist become the way for preventing or delaying aortic aneurysm progression in patients. More studies will be needed to clarify this drug effects in detail.
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http://dx.doi.org/10.1007/s11748-015-0576-1DOI Listing
October 2015

Impact of newly developed, next-generation artificial endocrine pancreas.

J Med Invest 2015 ;62(1-2):41-4

Department of Anesthesiology, Tokushima University Hospital.

Background: Recent studies have shown that strict perioperative blood glucose management may reduce mortality and morbidity in critically ill adult patients. The purpose of this study was to assess the accuracy and efficacy of the intraoperative application of a newly developed, next-generation artificial endocrine pancreas (STG-55, Nikkiso Co., Ltd., Tokyo, Japan).

Methods: Twenty patients scheduled to undergo surgery were enrolled in this study. The STG-55 is designed to be more user-friendly than its conventional counterpart (STG-22) while maintaining the latter's fundamental functions, such as a closed-loop system using algorithms for insulin and glucose infusion. After anesthetic induction, a 20G intravenous catheter was inserted into a peripheral forearm vein and connected to a continuous blood glucose monitor. The resultant 105 scores for paired blood glucose values were compared by Bland-Altman analysis.

Results: Stable blood glucose values were maintained automatically, and there were no complications related to use of the STG-55. A close correlation (r=0.96) was observed between continuous glucose measurements using the STG-55 and conventional intermittent glucose measurements. The difficulty of manipulation using this system was decreased by improved preparation procedures.

Conclusion: The glycemic control system using the STG-55 could provide an alternative way to achieve effective and safe perioperative glycemic control.
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http://dx.doi.org/10.2152/jmi.62.41DOI Listing
December 2016

[Reconstruction of pulmonary blood flow in the Norwood procedure; Blalock-Taussig shunt; from bench to surgery].

Kyobu Geka 2014 Apr;67(4):274-7

Department of Cardiovascular Surgery, The University of Tokushima, Tokushima, Japan.

Although the right-ventricle to pulmonary artery( RV-PA) shunt as a source of pulmonary blood supply of Norwood procedure has improved early outcomes, disadvantages including right ventricular dysfunction or arrhythmias have been reported. So it has been still remained controversial whether BT shunt or RV-PA conduit should be selected. We examined the influence of Blalock-Taussig( BT) shunt size on regulation of the pulmonary blood flow in experimental model of a univentricular heart to determine the specific guidelines regarding suitable shunt size in the Norwood procedure. The canine univentricular heart model with the ratio of shunt size to body weight (SS/BW) of 0.8 to 1.1 showed significant negative correlation between the pulmonary/systemic blood flow ratio( Qp/Qs)and arterial PCo2, but those with SS/BW of 1.1 to 1.4 did not. Similar phenomena were shown with the grouped data on relationship between the Qp/Qs and inspired oxygen fraction. These findings imply that when SS/BW is 0.8 to 1.1, the Qp/Qs is controllable by physiologic respiratory manipulations. In the context of our clinical experiences, SS/BW of 0.9 to 1.0 is considered a useful index for suitable BT shunt in the Norwood procedure.
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April 2014

Gastrointestinal hemorrhage caused by aortoenteric fistula due to aortic aneurysm.

Asian Cardiovasc Thorac Ann 2014 Jun 12;22(5):629. Epub 2013 Jun 12.

Department of Cardiovascular Surgery, Institute for Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.

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http://dx.doi.org/10.1177/0218492313478434DOI Listing
June 2014

Iliac access conduit facilitates endovascular aortic aneurysm repair and ipsilateral iliofemoral bypass.

J Med Invest 2014 ;61(1-2):204-7

Department of Cardiovascular Surgery, Institute of Health Biosciences, the University of Tokushima Graduate School.

It may be difficult to access a route to deliver a stent-graft for abdominal aortic aneurysm in high-risk patients with bilateral iliofemoral occlusive disease. These two patients underwent both endovascular aortic aneurysm repair by a modified iliac access conduit technique and sequential ipsilateral iliofemoral artery bypass using the conduit, which provided excellent results. The iliac access conduit facilitates endovascular aortic aneurysm repair and ipsilateral iliofemoral bypass of high-risk patients with abdominal aortic aneurysm and bilateral iliofemoral occlusive disease.
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http://dx.doi.org/10.2152/jmi.61.204DOI Listing
April 2015

Increased number of Hassall's corpuscles in myasthenia gravis patients with thymic hyperplasia.

J Neuroimmunol 2014 Apr 28;269(1-2):56-61. Epub 2014 Jan 28.

Department of Neurology, Institute of Health Bioscience, Graduate School of Medical Sciences, The University of Tokushima, Tokushima, Japan.

The thymus is implicated as an organ that contributes to autoimmunity in myasthenia gravis (MG) patients. Hassall's corpuscles (HCs) are assumed to represent the terminally differentiated stage of medullary thymic epithelial cells (mTECs). By using multicolor immunohistofluorescence analysis, we examined HCs in thymuses that were therapeutically excised from MG (+) and MG (-) patients. We found that the number of HCs per unit area of the thymic medulla was significantly elevated in the thymuses of MG (+) patients with thymic hyperplasia. CCL21 expression increased in the hyperplastic MG thymuses. We speculate that the altered differentiation of mTECs is associated with the thymic hyperplasia and the onset of MG.
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http://dx.doi.org/10.1016/j.jneuroim.2014.01.011DOI Listing
April 2014

Massive tricuspid regurgitation due to pacemaker-lead puncture of the tricuspid valve: successful diagnosis by 3-dimensional echocardiography.

J Med Ultrason (2001) 2014 Jan 31;41(1):69-71. Epub 2013 May 31.

Department of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima, 770-8503, Japan.

An 83-year-old woman presented to our echocardiographic center with symptoms of right heart failure. A dual-chamber DDDR pacemaker had been implanted 9 years earlier. Two-dimensional echocardiography revealed right atrial and ventricular enlargement and massive tricuspid regurgitation with immobilization of the anterior leaflet of the tricuspid valve. Three-dimensional transesophageal echocardiography showed that the pacemaker lead had punctured the leaflet. These echocardiographic findings were confirmed during surgery. The pacemaker lead was transected and removed, and pericardial patch closure of the leaflet hole and tricuspid annuloplasty were performed. The mechanism of regurgitation was elucidated by real-time three-dimensional echocardiography, and surgical repair was straightforward.
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http://dx.doi.org/10.1007/s10396-013-0459-yDOI Listing
January 2014

HMGB1 plays a critical role in vascular inflammation and lesion formation via toll-like receptor 9.

Atherosclerosis 2013 Dec 2;231(2):227-33. Epub 2013 Oct 2.

Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima-city, Tokushima 770-8503, Japan; Department of Pediatrics, University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Objective: Endogenous ligands such as high-mobility group box 1 (HMGB1) and nucleic acids are released by dying cells and bind to Toll-like receptors (TLRs). As TLR9 is involved in both microbial and sterile inflammation by detecting both bacterial and endogenous DNA, we investigated its role in inflammation and lesion formation in a mouse model of vascular injury.

Methods And Results: C57BL/6 (WT) and TLR9 KO mice were subjected to wire-mediated vascular injury. Anti-HMGB1 antibody and purified HMGB1 protein were chronically delivered around the injured arteries by gelatin hydrogel, and neointima formation at 4 weeks after injury was evaluated. In addition, the same vascular injury was performed in bone-marrow chimeric mice (WT bone marrow into TLR KO mice; TLR9 KO bone marrow into WT mice). We also evaluated the production of inflammatory cytokines by mouse macrophages in response to HMGB1 and CpG-ODN. In wild-type mice after vascular injury, anti-HMGB1 antibody significantly reduced neointima formation and HMGB1 protein accelerated neointima hyperplasia. HMGB1 failed to accelerate lesion formation in TLR9 KO mice. The bone marrow transplantation study revealed that TLR9 in bone marrow-derived cells played a fundamental role in neointima formation. In vitro, HMGB1 and CpG-ODN synergistically induced the production of inflammatory cytokines by macrophages.

Conclusions: HMGB1 serves as an endogenous mediator of inflammation and lesion formation via the TLR9 pathway in response to vascular injury. Blockade of HMGB1 and/or TLR9 may represent a novel approach to treating atherosclerosis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2013.09.010DOI Listing
December 2013

Usefulness of central venous oxygen saturation monitoring during bidirectional Glenn shunt.

J Med Invest 2013 ;60(3-4):272-5

Department of Anesthesiology, Tokushima University Hospital.

A PediaSat™ oximetry catheter (PediaSat: Edwards Lifesciences Co., Ltd., Irvine, CA, U. S. A.), which facilitates continuous measurement of central venous oxygen saturation (ScvO2), may be useful for surgery for pediatric congenital heart disease. We used PediaSat during a bidirectional Glenn shunt. The patient was a 13-month-old boy. Under a diagnosis of left single ventricle (pulmonary atresia, right ventricular hypoplasia, atrial septal defect) and residual left aortic arch/left superior vena cava, a modified right Blalock-Taussig shunt was performed. Cyanosis deteriorated, so a bidirectional Glenn shunt was scheduled. After anesthesia induction, a 4.5 Fr double-lumen (8 cm) PediaSat was inserted through the right internal jugular vein for continuous ScvO2 monitoring. Furthermore, the probe of a near-infrared, mixed blood oxygen saturation-measuring monitor was attached to the forehead for continuous monitoring of the regional brain tissue mixed blood oxygen saturation (rSO2) (INVOS™ 5100C, Covidien; Boulder, CO, U. S. A.). Blockage of the right pulmonary artery and right superior vena cava decreased the oxygen saturation, ScvO2, and rSO2, but increased the central venous pressure. Although changes in ScvO2 were parallel to those in rSO2, the former showed more marked changes. A combination of ScvO2 and rSO2 for monitoring during Glenn shunt may be safer.
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http://dx.doi.org/10.2152/jmi.60.272DOI Listing
August 2014

Novel blood sampling method of an artificial endocrine pancreas via the cardiopulmonary bypass circuit.

J Artif Organs 2013 Dec 30;16(4):508-9. Epub 2013 Aug 30.

Department of Anesthesiology, Tokushima University Hospital, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan,

We tried to perform continuous blood glucose monitoring during cardiovascular surgery involving cardiopulmonary bypass using an artificial endocrine pancreas (STG-22 or -55; Nikkiso, Tokyo, Japan); however, we often encountered problems during these procedures because insufficient blood was obtained for monitoring. Thus, we started performing the blood sampling via the venous side of the cardiopulmonary bypass circuit. As a result, continuous blood glucose monitoring using an artificial endocrine pancreas was proven to be stable and reliable during cardiovascular surgery involving cardiopulmonary bypass.
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http://dx.doi.org/10.1007/s10047-013-0725-1DOI Listing
December 2013

Role of macrophage-derived hypoxia-inducible factor (HIF)-1α as a mediator of vascular remodelling.

Cardiovasc Res 2013 Sep 10;99(4):705-15. Epub 2013 Jun 10.

Department of Cardiovascular Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.

Aims: Excessive vascular remodelling leads to progression of a wide range of vasculopathies, and the immune response to intimal injuries is crucial in this process. This vascular remodelling occurs in the hypoxic microenvironment and is closely related to the immune system. Macrophages play a key role in immunological-cell-mediated arterial remodelling. In this study, we clarified the role of macrophage-derived hypoxia-inducible factor (HIF-1α) in vascular remodelling.

Methods And Results: Wire-induced femoral arterial injury was inflicted in mice lacking the macrophage-specific HIF-1α gene and in their wild-type counterparts. The mutant mice showed both suppressed wire-induced neointimal thickening and decreased infiltration of inflammatory cells in the adventitia, compared with wild-type mice. Studies to clarify the mechanism of restrained vascular remodelling in the mutant mice revealed decreased production of pro-inflammatory cytokines by the activated macrophages and suppressed macrophage migration activity in the mutant mice. Gene expressions of the HIF-1α-deficient macrophages positively correlated with the phenotypic profile of M2 macrophages and negatively correlated with that of M1 macrophages.

Conclusion: Our results show that HIF-1α in macrophages plays a crucial role in promoting vascular inflammation and remodelling. As decreasing HIF-1α activity in macrophages may prevent the progression of vascular remodelling, HIF-1α may be a possible therapeutic target in vascular diseases.
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http://dx.doi.org/10.1093/cvr/cvt146DOI Listing
September 2013

Techniques and results in the management of multiple muscular trabecular ventricular septal defects.

Gen Thorac Cardiovasc Surg 2013 Jul 5;61(7):367-75. Epub 2013 Jun 5.

Department of Cardiovascular Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.

The management of patients with multiple muscular trabecular ventricular septal defects (VSDs) remains controversial. In the past two decades, innovative techniques including a right ventricular apical infundibulotomy and transcatheter, intraoperative and perventricular device closure have been exploited, and essential right atrial approach and limited apical left ventriculotomy have also been refined. However, specific management guidelines for this difficult disease have not been established. In this article, the benefits and drawbacks of each technique are reviewed and discussed. Primary repair for infants with multiple muscular trabecular VSDs was associated with good late outcomes. The right atrial approach was satisfactory for all muscular VSDs, excluding apical defects that were well seen through a limited apical ventriculotomy. Surgical closure of apical defects could be achieved safely and completely in early infancy through a limited apical left ventriculotomy or a right ventricular apical infundibulotomy. Further follow-up and prudent evaluations of ventriculotomy-associated morbidities are needed. Pulmonary artery banding should be limited to a small infant with complex associated defects. Percutaneous device closure, the most desirable option, is impractical due to limitations between the delivery system and access route. Intraoperative device closure appears less successful than device closure in the catheterization laboratory. Perventricular device closure has a significant advantage of being a non-bypass procedure approach. A less invasive strategy for "true" Swiss cheese septum is needed. All may have an important role, and results obtained by using these techniques are encouraging. These hybrid approaches will promise future success on management guidelines of multiple muscular trabecular VSDs.
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http://dx.doi.org/10.1007/s11748-013-0267-8DOI Listing
July 2013

Protective effects of selective mineralocorticoid receptor antagonist against aortic aneurysm progression in a novel murine model.

J Surg Res 2013 Nov 23;185(1):455-62. Epub 2013 May 23.

Department of Cardiovascular Surgery, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.

Background: The optimal medical management to delay the progression of aortic aneurysms has not been fully clarified, and the only standard treatment at present is antihypertensive therapy. Previous studies have shown beneficial effects of selective mineralocorticoid receptor (MR) antagonists on cardiovascular remodeling. The aim of the present study was to investigate the effect of a selective MR antagonist on aortic aneurysm progression.

Methods: Seven-week-old C57BL/6J male mice were administered with angiotensin II and β-aminopropionitrile for 4 weeks. The mice received either vehicle or eplerenone, a selective MR antagonist (100 mg/kg daily) every day by gavage, starting at 7 weeks of age. The production of inflammatory cytokines in cultures of high mobility group box-1-stimulated macrophages with or without a MR antagonist was also analyzed using an enzyme-linked immunosorbent assay.

Results: Although no differences were found in the peak systolic blood pressure between the experimental groups, the mice in the eplerenone group showed a significant reduction in aneurysm development. On histologic analysis, coarse and stretched elastic fibers were markedly improved in the aortic wall in the eplerenone group. Real-time polymerase chain reaction of both aortic wall and perivascular adipose tissue demonstrated the expression of tumor necrosis factor-α, interleukin-6, and matrix metalloproteinase-2 was significantly decreased in eplerenone group, and that of monocyte chemoattractant protein-1 in the aortic wall was also significantly decreased. Macrophage infiltration in the aortic wall and perivascular adipose tissue in the eplerenone group was also significantly decreased. The production of tumor necrosis factor-α and interleukin-6 in macrophage culture, which was stimulated by high mobility group box-1 and CpG oligodeoxynucleotides, was also significantly decreased in the eplerenone group.

Conclusions: Eprelenone suppressed aortic aneurysm progression through an anti-inflammatory effect. Thus, selective MR antagonists might be effective in preventing the progression of aortic aneurysms.
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http://dx.doi.org/10.1016/j.jss.2013.05.002DOI Listing
November 2013
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