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Dexmedetomidine suppresses serum syndecan-1 elevation and improves survival in a rat hemorrhagic shock model
Get PDF浜松医科大学博士（医学）J-STAGEにて、最終版の公開あり。The final version of this article is available on J-STAGE.doctoral医学系研究科Hemorrhagic shock causes vascular endothelial glycocalyx (EGCX) damage and systemic inflammation. Dexmedetomidine (DEX) has anti-inflammatory and EGCX-protective effects, but its effect on hemorrhagic shock has not been investigated. Therefore, we investigated whether DEX reduces inflammation and protects EGCX during hemorrhagic shock. Anesthetized Sprague-Dawley rats were randomly assigned to five groups (n=7 per group): no shock (SHAM), hemorrhagic shock (HS), hemorrhagic shock with DEX (HS+DEX), hemorrhagic shock with DEX and the α7 nicotinic type acetylcholine receptor antagonist methyllycaconitine citrate (HS+DEX/MLA), and hemorrhagic shock with MLA (HS+MLA). HS was induced by shedding blood to a mean blood pressure of 25-30 mmHg, which was maintained for 30 min, after which rats were resuscitated with Ringer’s lactate solution at three times the bleeding volume. The survival rate was assessed up to 3 h after the start of fluid resuscitation. Serum tumor necrosis factor-alpha (TNF-α) and syndecan-1 concentrations, and wet-to-dry ratio of the heart were measured 90 min after the start of fluid resuscitation. The survival rate after 3 h was significantly higher in the HS+DEX group than in the HS group. Serum TNF-α and syndecan-1 concentrations, and the wet-to-dry ratio of heart were elevated by HS, but significantly decreased by DEX. These effects were antagonized by MLA. DEX suppressed the inflammatory response and serum syndecan-1 elevation, and prolonged survival in rats with HS.doctoral thesi
Intra-Left Ventricular Hemodynamics Assessed with 4D Flow Magnetic Resonance Imaging in Patients with Left Ventricular Thrombus
Get PDF浜松医科大学博士（医学）doctoral医学系研究科Left ventricular thrombus (LVT) has been identified to be crucial in patients with reduced ejection fraction (EF). Three-dimensional cine phase-contrast magnetic resonance imaging (4D flow MRI) can visualize the intra-LV vortex during diastole and quantify the maximum flow velocity (Vmax) at the apex. In this study, we investigated whether the change in the intra-LV vortex was associated with the presence of LVT in patients with cardiac disease.
In total, 36 patients (63.5±11.9 years, 28 men, 12/24 with/without LVT) with diffuse LV dysfunction underwent 4D flow MRI. The relative vortex area using streamline images and Vmax of blood flow toward the apex at the apical left ventricle were evaluated. The correlation between the relative vortex area and Vmax was assessed using Pearson’s correlation coefficient. The ability to detect LVT was evaluated using the area under the curve (AUC) of the receiver operating characteristic.
The relative vortex area was found to be smaller (27±10% versus 45±11%, P=0.000026), whereas Vmax at the apical left ventricle was lower (19.1±4.4 cm/second versus 27.4±8.9 cm/second, P=0.0006) in patients with LVT. Vmax at the apical left ventricle demonstrated significant correlations with the relative vortex area (r=0.43, P=0.01) and relative transverse length of the vortex (r=0.45, P=0.007). The AUC was 0.91 for the relative vortex area, whereas it was 0.80 for Vmax in the apical left ventricle.
A smaller LV vortex and lower flow velocity at the LV apex were associated with LVT in patients with reduced EF.doctoral thesi
Focal atrial tachycardia originating in the distal portion of the right atrial appendage aneurysm
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Development of neonatal intensive care and medical systems over 18 years at the Perinatal Center of Hamamatsu University Hospital
Get PDF浜松医科大学医学部附属病院では，2003年に周産母子センターが開所され，同時に6床の新生児特定集中治療室（NICU）が開設された．その後6床の新生児治療回復室（GCU）が増設され，2013年にNICUが9床に増床され現在に至っている．新生児入院数は2003年度の97例から2020年度は316例に増加し，人工呼吸器管理件数は21件から105件に増加した．
18年間の超低出生体重児入院総数は100例で，超低出生体重児および超早産児の死亡率は，2010年の全国調査と比較して遜色ないものであった．
2003～2011年度（前期）と 2012～2020年度（後期）の新生児診療実績を比較すると，分娩件数，新生児入院数，超低出生体重児入院数，人工呼吸器管理件数，一酸化窒素吸入療法件数，新生児低体温療法件数，未熟児網膜症治療件数，新生児外科手術件数は後期で有意に増加していた．多変量解析の結果，前・後期の差異に影響力を持つ因子は分娩数であった．
新生児診療体制について前・後期を比較すると，新生児専従医数，常勤医数，新生児専門医数，新生児専攻医数，研修医数は有意に後期が多く，月間当直回数は有意に後期が少なかった．多変量解析によると，前・後期の差異に影響力を持つ因子は新生児専門医数であった．
今後さらに重症化する新生児診療および医師の働き方改革に対応するためには，診療体制の充実と人材育成を推進していく必要がある．journal articl
An infantile case of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency presenting recurrent severe hypoglycemia
Get PDFミトコンドリア3-ヒドロキシ-3-メチルグルタリル-CoA（HMG-CoA）合成酵素欠損症は，HMGCS2遺伝子の異常による常染色体劣性遺伝性ケトン体産生異常症であり，非ケトン性低血糖症，意識障害，肝腫大，代謝性アシドーシスを引き起こす．
月齢7ヵ月，胃腸炎症状と経口摂取不良時に血糖値10mg/dL未満の低血糖を初発し，その後反復．低血糖発症時の検査で，肝逸脱酵素上昇と遊離脂肪酸／総ケトン体比11.2と著明高値を認め，HMGCS2遺伝子に，c.1175C>T（p.Ser392Leu）と c.437T>C（p.Met146Thr）の複合ヘテロ接合性変異を同定し， HMG-CoA合成酵素欠損症と診断した男児例を報告する．
HMG-CoA合成酵素欠損症の診断確定には遺伝子解析が有用であるが，特徴的な有機酸分析やアシルカルニチン分析のパターンがないため，本疾患を疑って検査しないと診断は不可能であり，多くの未診断例が存在すると推定されている．診断が確定され，代謝ストレス時の飢餓を予防すれば，一般に予後良好とされているため，確実に診断することが重要である．journal articl
A case of Port-site Hernia after Retroperitoneal Laparoscopic Para-aortic Lymphadenectomy for Early-stage Endometrial Cancer
Get PDF本邦において後腹膜鏡下傍大動脈リンパ節郭清術は未だ一般的な手技とは言い難く、合併症報告は少ない。我々は、後腹膜鏡下傍大動脈リンパ節郭清術を含む子宮体癌根治手術を施行後に発症したポートサイトヘルニアを経験した。症例は69歳 BMI 23.9kg/m2の女性で、不正性器出血を自覚し当院を紹介受診した。術前精査にて子宮体癌（類内膜癌Grade1、ⅠB期）が想定されたため、腹腔鏡下子宮全摘術、両側付属器切除術、骨盤リンパ節郭清術、傍大動脈リンパ節郭清術を行った。傍大動脈リンパ節郭清には後腹膜アプローチを用いた。術後3日目より腹部膨満感と反復する嘔吐を発症し腹部CT検査にて、左下腹部の12mmポート孔に小腸が嵌頓し、腸閉塞を発症していたためポートサイトヘルニアと診断し、開腹下にイレウス解除術が行われた。筋膜は縫合されていたにも関わらず、腹膜のポート孔に小腸が嵌頓し、後腹膜鏡にて剥離した腹膜と筋膜の隙間に小腸が嵌入していた。
後腹膜鏡下リンパ節郭清を含む子宮体癌手術の際には、ポート孔腹膜の確実な閉鎖が必要と考えられた。Retroperitoneal laparoscopic para-aortic lymphadenectomy is not yet a common technique in Japan. Perhaps for this reason, reports of complications associated with the procedure are rare. We present a case of a 69-year-old woman with a body mass index of 23.9kg/m2 who presented with irregular genital bleeding. She was diagnosed with endometrial cancer (endometrioid carcinoma grade 1, stage 1B) and underwent laparoscopic hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy, and para-aortic lymphadenectomy. Para-aortic lymphadenectomy was performed via a retroperitoneal approach. On the third postoperative day, the patient developed abdominal distension and vomited repeatedly. She was diagnosed with port-site hernia at the left iliac fossa based on enhanced abdominal computed tomography findings, and underwent laparotomy to relieve obstruction of the small bowel. This operation revealed herniation of the intestine into the peritoneal wall, which had been punctured during trocar insertion. Although the wound fascia had been kept sutured, the small bowel had entered into an extraperitoneal space under the fascia transversalis that had formed during retroperitoneal para-aortic lymphadenectomy. To avoid such complications in the future, closure of the peritoneal wall is mandatory after minimally invasive surgery for endometrial cancer including retroperitoneal laparoscopic para-aortic lymphadenectomy.journal articl
Survival impact of perioperative changes in prognostic nutritional index levels after esophagectomy
Get PDFBackground The correlation between perioperative changes in nutritional status during esophagectomy and prognosis remains unclear. This study aimed to evaluate the impact of changes in prognostic nutritional index levels during the perioperative period on esophageal cancer patient survivals.
Methods From January 2009 to May 2019, 158 patients with esophageal squamous cell carcinoma were enrolled. From the time-dependent ROC analysis, the cutoff values of preoperative and postoperative prognostic nutritional index levels were 46.9 and 40.9. Patients were divided into preoperative-high group (Group H) and preoperative-low group (Group L). Then, patients in Group L were divided into preoperative-low and postoperative-high group (Group L?H) and preoperative-low and postoperative-low group (Group L?L). Long-term outcomes and prognostic factors were evaluated.
Results Patients in Group L had significantly worse overall survival than those in Group H (p=0.001). Patients in Group L?L had significantly worse overall survival than those in Group L?H (p=0.023). However, there was no significant difference in overall survival between Groups H and L?H (p=0.224). In multivariable analysis, advanced pathological stage (hazard ratio 10.947, 95% confidence interval 2.590?46.268, p=0.001) and Group L?L (hazard ratio 2.171, 95% confidence interval 1.249?3.775, p=0.006) were independent predictors of poor overall survival.
Conclusions Patients in Group L?H had a good prognosis, similar to those in Group H. This result indicated that increasing the postoperative prognostic nutritional index level sufficiently using various intensive perioperative support methods could improve prognosis after esophagectomy in patients with poor preoperative nutritional status.journal articl
Therapeutic monitoring of adalimumab at non-trough levels in patients with inflammatory bowel disease
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Impairment of the hypothalamus-pituitary-thyroid axis caused by naturally occurring GATA2 mutations in vitro
Get PDF浜松医科大学博士（医学）doctoral医学系研究科The transcription factor GATA2 regulates gene expression in several cells and tissues, including hematopoietic tissues and the central nervous system. Recent studies revealed that loss-offunction mutations in GATA2 are associated with hematological disorders. Our earlier in vitro studies showed that GATA2 plays an essential role in the hypothalamus-pituitary-thyroid axis (HPT axis) by regulating the genes encoding prepro-thyrotropin-releasing hormone (preproTRH) and thyroidstimulating hormone β (TSHβ). However, the effect of GATA2 mutants on the transcriptional activity of their promoters remains unelucidated. In this study, we created five human GATA2 mutations (R308P, T354M, R396Q, R398W, and S447R) that were reported to be associated with hematological disorders and analyzed their functional properties, including transactivation potential and DNAbinding capacity toward the preproTRH and the TSHb promoters. Three mutations (T354M, R396Q, and R398W) within the C-terminal zinc-finger domain reduced the basal GATA2 transcriptional activity on both the preproTRH and the TSHb promoters with a significant loss of DNA binding affinity. Interestingly, only the R398W mutation reduced the GATA2 protein expression. Subsequent analysis demonstrated that the R398W mutation possibly facilitated the GATA2 degradation process. R308P and S447R mutants exhibited decreased transcriptional activity under protein kinase C compared to the wild-type protein. In conclusion, we demonstrated that naturally occurring GATA2 mutations impair the HPT axis through differential functional mechanisms in vitro.doctoral thesi
Desflurane anesthesia shifts the circadian rhythm phase depending on the time of day of anesthesia
Get PDF浜松医科大学博士（医学）doctoral医学系研究科Desflurane is one of the most frequently used inhalational anesthetics in clinical practice. A circadian rhythm phase-shift after general anesthesia with sevoflurane or isoflurane has been reported in mice, but few studies have reported this effect with desflurane. In the present study, we examined the rest/activity rhythm of mice by counting the number of running wheel rotations, and we found that desflurane anesthesia caused a phase shift in the circadian rhythm that was dependent on the time of day of anesthesia. We also found that desflurane anesthesia altered the relative mRNA expression of four major clock genes (Per2, Bmal, Clock, and Cry1) in the suprachiasmatic nucleus (SCN). These results are important for elucidating the effects of desflurane on the SCN, which is the master clock for the mammalian circadian rhythm. Further studies on the relationship between anesthesia and circadian rhythm may lead to the prevention and treatment of postoperative complications related to circadian rhythms.doctoral thesi