DECEMBER

2023

VOLUME 48

NUMBER 2

投稿

1. 本誌には金沢医科大学医学会正会員の総説，原著，症例報告および短報を掲載するが，正会員以外でも編集委員会の承認があれば掲載することができる。そのほか学会抄録，雑報，本学学位論文の審査要旨を掲載することがある。
2. 倫理規定：投稿論文は基礎研究，臨床研究のいずれにおいても生命倫理に十分な配慮がなされたものであること。また，個人情報の保護のために必要な処置を講じたものでなければならない。
1) ヒトを対象とする研究はヘルシンキ宣言の理念を踏まえ，「臨床研究法」「人を対象とする生命科学・医学系研究に関する倫理指針」および金沢医科大学等の人を対象とする医学系研究に関する規定を遵守し，金沢医科大学等の各倫理審査委員会の承認を得た上で実施した旨を明記すること。特に，「患者の権利，プライバシーの保護」に努め，論文作成に際して，下記の指針を遵守すること。
a. 患者個人の特定が可能となる氏名やイニシャル，住所，カルテ番号，
入院番号等は記載しない。
b. 患者の職業や紹介先施設名・診療科名などについても，患者個人が特定される可能性のある場合は記載しない。
c. 日付は，患者個人を特定できないと判断される場合でも，年月までの記載とする。
d. 顔写真を掲載する場合は，患者個人を特定できぬよう目隠しを付す。
e. 以上の配慮をしても患者個人が特定される場合は，論文内容を提示したうえで，患者本人 ( または遺族か代理人，小児では保護者 ) から発表に関する同意を得ること ( 同意書のコピーは投稿時に添付すること )。
2) 動物実験は「研究機関等における動物実験等の実施に関する基本指針( 文部科学省 )」もしくは「厚生労働省の所管する実施機関における動物実験等の実施に関する基本指針」の規定を遵守し，金沢医科大学等の動物実験委員会の承認を得た上で実施した旨を明記すること。遺伝子組換
え動物実験においては，金沢医科大学等の組換え DNA 実験安全委員会の承認を得た上で実施した旨を明記すること。
3) 遺伝性疾患やヒトゲノム・遺伝子解析を伴う症例の報告では，「人を対象とする生命科学・医学系研究に関する倫理指針」および金沢医科大学
等のヒトゲノム・遺伝子解析研究に関する規定を遵守し，金沢医科大学
等の倫理審査委員会の承認を得た上で実施した旨を明記すること。
4) 遺伝子治療臨床研究に関しては，「遺伝子治療等臨床研究に関する指針」の規定を遵守すること。
5) その他，国が告示した倫理指針に該当する研究は，各指針にそれぞれ合致している旨を明記すること。
3. 原稿様式：原稿は英文または和文とし，標題，要約，キーワード，ランニ
ングタイトル，本文，図，表，文献を基本とする ( 本文が和文の場合のみ，
英文抄録が必要 )。また原稿は，A4 版用紙に Microsoft Word で作成した文書ファイルまたは PDF とし，図表は Microsoft Word，Microsoft Excel，Microsoft PowerPoint 等で作成したファイルとする。図・写真は 300dpi 以上の解像度で作成された JPEG，TIFF および PNG 形式のファイルでも受け付ける。原稿は，文字サイズ 11 ポイント，英文は 1 ページ当たり 20 行で 300
語程度，和文は 40 字 ×20 行を目安に作成すること。また用紙の上下左右は十分にあけ，用紙の下余白にページ番号を付記すること。原稿の長さは原則として，本文，図，表を合わせて 30 枚 ( 和文 20,000 字，英文 8,000 語 ) 以
内とすること。本文が英文の場合は半角入力とし，和文の場合は横書き，
ひらがな，現代かなづかいとし，原則として当用漢字を使用する。和文中の外国語 ( 薬物一般名等 ) はすべて英語綴りの小文字とし，文頭・人名・固有名詞・動植物学名・ドイツ語名詞・商品名・製品名は大文字ではじめる。
4. 標題：原稿第 1 頁に標題，著者名，所属の順で記入し，掲載希望区分を左肩に記入する。連絡著者名の右肩にアスタリスク (＊) を付し，連絡先として，連絡著者の所属機関・氏名・住所および E-mail アドレス等を記載する。
5. 要約：本文が英文の場合は 300 語以内，和文の場合は 600 字以内の要約をつける。論文の概要が具体的にわかるように，目的・対象と方法・結果・
結論，または背景・症例・所見・結論などに分けて記載する。
6. キーワード：5 個以内のキーワードをつけること。
7. ランニングタイトル：本文が英文の場合は英文 ( 半角 80 字以内 )，和文の場合は和文 ( 全角 40 字以内 ) のランニングタイトルを記入すること。
8. 本文：実験研究は，緒言 ( はじめに )，実験方法，結果 ( 成績 )，考察 ( 考按 )に区分する。臨床報告は，緒言 ( はじめに )，症例，考察 ( 考按 ) に区分する。
金沢医科大学等の倫理審査委員会の承認を得た研究である場合は，本文中にその旨を明記すること。倫理規定を逸脱していると編集委員会が判断したものについては，査読の結果にかかわらず不採択とすることがある。和文の場合，外国の人名，地名，物質名などは原則として外国語そのままを用いる。ただし，慣用の和名がある場合はカタカナで書く。適当な日本語訳のない用語は原綴を用いる。動植物，微生物などの学名はイタリック体で記載する。薬品名は原則として日本語の一般名を用いる。特殊な，あるいは特定分野のみで用いられている単位，符号，略語ならびに表現には必ず簡単な説明を加える。数字は原則としてアラビア数字を使用するが，「十数回」，「百分率」などの場合は例外とする。度量衡の記載は原則としてメートル法による。本文中に見出し符号を付す場合は，1，1)，(1)，i) の順に付すこと。ただし，緒言，実験方法等の論文構成の各項目には付けないこととする。しばしば繰り返される語は略語を用いてもよいが，初出の際は規程

完全な用語を用い，以下に略語を使用することを明記する。統計処理を行った際には統計学的検定法を明記する。
9. 利益相反 (conflict of interest) の開示：投稿論文の内容に関する利益相反の有無を筆頭著者，共著者全員について論文の末尾に明記すること。またすべての著者は本誌所定の利益相反自己申告書を別途添付すること。
10. 文献：本文中の文献引用は，引用順に一連番号を本文と同行に (1)，(1-3)，(1，3-5) などと記し，肩付とはしない。文献欄の記載は，下記の要領により番号順に配列する。
1) 雑誌の場合は著者名 ( 筆頭著者から 3 名までとし，3 名をこす場合は「ほか」または「et al」と記載する )，標題，掲載誌名 ( 略名 )，発行年 ( 西暦 )，巻数，頁数 ( 開始頁 - 終了頁 ) の順に記載する。
・ Johnstone BM, Taylor KJ, Boyle AJ: Mechanics of the Guinea pig cochlea.
J Acoust Soc Am 1970; 47: 504-8.
・ Ferguson B, Matyszak MK, Esiri MM et al: Axonal damage in acutemultiple sclerosis. Brain 1997; 120: 393-9.
・ 柴田整一 , 三村信英 , 木村二郎ほか : 進行しない所謂“慢性腎炎”．日腎誌 1962; 4: 31-7.
2) 単行本の場合は著者名 , 標題 , 編集者名 , 書名 , 版数 , 発行所所在地 , 発行
所 , 発行年 , 頁数 ( 開始頁 - 終了頁 ) の順とする。
・ Mostofi FK: Benign hyperplasia of the prostate gland. In Campbell MF,
Harrison JH (Eds), Urology (3rd ed), Philadelphia, WB Saunders, 1970;
1065-129.
・ 丸野義和 : 体液平衡異常と腎臓 , 東京 , 南江堂 , 1970; 75-7.
・ 河野祐治 , 吉良潤一 : HIV-1 と免疫変化概説 . 杉田秀夫 , 田平武 ( 編 ),HIV-1 感染による神経障害の診療マニュアル , 東京 , 新興医学出版社 ,1997; 118-37.
3) インターネット上の資料や情報を引用する場合，URL とアクセスした年月日を記載する。
・ 厚生労働省：がん対策推進基本計画 , http://www.mhlw.go.jp/bunya/
kenkou/dl/gan_keikaku02.pdf (2016 年 7 月 1 日にアクセス ) ．
4) 著者名が人名でないときは次のようにする。
・ 日本病理学会編 : 日本病理剖検輯報 , 14 輯 , 東京 , 日本病理剖検輯報刊行
会 , 1972.
5) 引用雑誌の略名は，MEDLINE または Index Medicus および医学中央雑誌収載誌目録によること。
6) オンラインジャーナル (Epub のみ ) および早期公開 (Epub on ahead) の場合，電子出版 (Epub) 年月日や DOI があれば掲載する。
7) 原則として，特殊な報告書，投稿中原稿，私信などで一般的に入手不可
能な資料は文献としての引用を差し控えること。
11. 図：出来上がり寸法は横幅 8 ㎝にするか，17 ㎝にするかを指定のこと。
12. 表：原則として本文が英文の場合は英文，和文の場合は和文 ( ただし，和文で表現し難い語句および字句は例外とする ) にて作成する。
13. 図の説明：原則として本文が英文の場合は英文，和文の場合は和文にて別紙に一括する。
14. 英文抄録：本文が和文の場合は，英文の標題，氏名，所属，要約 ( 総説・原著の場合は 400 語以内，症例報告・短報の場合は 200 語以内 )，キーワード，連絡先を記載する。
15. 原稿の採否および掲載の順序は編集委員会で決定する。
16. 原稿の校正は初校・再校とも著者校正とし，校正時の大幅な変更は許されない。また校正期日は厳守のこと。
17. 投稿論文内容は他誌に発表されていないものに限る。また投稿論文の二重投稿や同時投稿は認めない。ただし，本誌掲載和文論文の他誌への英文化再掲載 (secondary publication) 等については編集委員会が特に認めた場合はこの限りではない。
18. 掲載費のうち，総説では組上がり 10 頁まで，原著では 8 頁まで，症例報告・短報では 5 頁までを無料とする。超過分および別冊はすべて著者の負担とするが，依頼原稿の超過分は無料とする。なお，原稿にカラー写真等のある場合，版代は著者の負担とする。
19. 原稿提出：紙原稿 1 部，原稿の電子データ，投稿申込書，チェックリスト，
誓約書，利益相反自己申告書を下記あてに提出する。論文が受理されたときは，最終版の電子データ ( 図表，写真含む ) を提出すること。
20. 本誌に掲載された著作物の著作権は，本医学会に帰属する。
＜連絡先＞ 〒 920-0293 石川県河北郡内灘町大学 1 − 1
金沢医科大学内 金沢医科大学雑誌編集委員会
TEL．076-286-2211 ( 内線 7242)
E-mail: hrc-jimu@kanazawa-med.ac.jp
この規定は 1979 年 1 月一部改正した。 この規定は 1985 年 5 月一部改正した。
この規定は 1986 年 11 月一部改正した。 この規定は 1988 年 2 月一部改正した。
この規定は 1989 年 9 月一部改正した。 この規定は 1995 年 2 月一部改正した。
この規定は 1997 年 2 月一部改正した。 この規定は 2000 年 3 月一部改正した。
この規定は 2003 年 3 月一部改正した。 この規定は 2013 年 4 月一部改正した。
この規定は 2020 年 2 月一部改正した。 この規程は 2022 年 3 月一部改正した。
以上

Submission Guidelines
1. This Journal publishes reviews, original articles, case reports, and shortreports by regular members of the Medical Society of Kanazawa Medical
University. It may also publish works by non-regular members if the Editorial
Board approves them. Conference abstracts, general news, and summaries
of Kanazawa Medical University theses are also published in the Journal.
2. Ethics Code: The manuscript in basic and clinical research must follow therelevant bioethical rules. In addition, the authors must protect the privacy of
personal information.
1) For experiments involving human subjects, the authors must understandthe Declaration of Helsinki principles and adhere to the Clinical Trials Act,
the Ethical Guidelines for Medical and Biological Research Involving
Human Subjects, and the guidelines for medical research involving humansubjects at Kanazawa Medical University or other institutes. The authors
must state that the research was carried out with the approval of therelated committee(s) of Kanazawa Medical University or other institutes.
In particular, the authors must follow the rules outlined below, to protect
the rights and privacy of the patients.
a. Do not include any information, such as patients’ names, initials,
addresses, medical record numbers, and hospitalization numbers that
could be used to identify individual patients.
b. Do not include any information, such as the patients’ occupations or thenames of referring institutions or departments that could be used to
identify the patients.
c. Even if the patient cannot be identified by the date, use month and year
instead.
d. Put black lines on the eyes of the patients’ photographs to prevent
identification of the patient.
e. When the patient can be identified despite the completion of all of thepreceding procedures, obtain the patient’s consent for publication. The
consent can be granted by bereaved family, deputies, or the child patient’s
guardians. At the time of submission, include a copy of the consent withthe manuscript.
2) For the animal experiments, the authors must follow the Guidelines for
Proper Conduct of Animal Experiments and Related Activities in
Academic Research Institutions issued by the Ministr y of Education,
Culture, Sports, Science and Technology or the Basic Guidelines for the
Conduct of Animal Experiments in Research Institutes by the Ministry of
Health, Labour and Welfare. The authors must state that the research was
car ried out after approval by the animal experiment committee ofKanazawa Medical University or other institutes. The authors must statethat the animal experiments with genetic recombination were carried out
after approval by the safety committee for recombinant DNA experiments
at Kanazawa Medical University or other institutes.
3) For reports of hereditar y disorders or cases involving human genome
and/or gene analysis, the authors must conform to the Ethical Guidelines
for Medical and Biological Research Involving Human Subjects, as well as
the guidelines on human genome/gene analysis research of Kanazawa
Medical University or other institutes. The authors must state that the
research was approved by the ethics review committee of Kanazawa
Medical University or other institutes.
4) For gene therapy clinical research, the authors must conform to the
Guideline for Gene Therapy Clinical Study.
5) For research that corresponds to the ethical guidelines by the Japanese
government, the authors must state that the research was carried out
properly according to the relevant guidelines.
3. Manuscript format: A title, an abstract, keywords, a running title, the main
text, figures, tables, and references are included in the manuscript. The text
must be in a file formatted in Microsoft Word or PDF and printed on A4
paper. Figures and tables should be created using Microsoft Word, Microsoft
Excel, Microsoft PowerPoint, or another software program. Figures andphotographs should be in JPEG, TIFF, or PNG format with a resolution of atleast 300 dpi. The text should be 11-point font, with 20 lines on a page, whichtakes approximately 300 words per page. There should be margins on thetop, bottom, left, and right sides of the page. Page numbers should be placedin the bottom margin. The manuscript should be no more than 30 pages
long, including text, figures, and tables (about 8,000 words).
4. Title: The title should be printed on the first page of the manuscript in thefollowing order: title, author(s) name(s), and affiliation(s). The publication
categor y should be located in the upper left corner. To the right of thecor responding author’s name, an asterisk (＊) should be added. The
corresponding author’s affiliation, name, address, and e-mail address must
be included.
5. Abstract: An abstract should be within 300 words. It should be divided into
the following sections: Purpose, Materials and Methods, Results, andConclusions or Background, Cases, Findings, and Conclusions.
6. Keywords: Provide up to five keywords.
7. Running title: Include a running title within 80 characters.
8. Main text: The following sections should be included in the research,
including experiments: Introduction, Methods, Results, and Discussion.

Introduction, Case, and Observations should be included in clinical reports(invention). The approval by Kanazawa Medical University’s or otherinstitutions’ ethical review committees should be stated in the text by theauthors. It should be noted that the manuscript might be rejected regardlessof peer review results when the Editorial Board determines that the authors
have violated the ethics. The authors should provide a brief explanation for
any units, symbols, abbreviations, and other expressions that are unique or
used only in particular fields. Heading codes in the text are as numbers in
the following order: 1, 1), (1), and i). These numberings do not apply tosection titles such as Introduction, Methods, and so on. For frequently
repeated terms, abbreviations may be used. To accomplish this, the term’s
name should be fully spelled out on its first appearance, with the statementthat it will be abbreviated in the future. The method of statistical processing
should be stated when it is used.
9. Disclosure of conflicts of interest: At the end of the text, all authors should
declare whether or not they have any conflicts of interest related to themanuscript. Individual authors must attach the self-report form of conflict ofinterest prescribed by the Journal.
10.References: References in the main text should be numbered as (1), (1-3),(1, 3-5) in the order of appearance. Superscripts should not be used forcitations in the main text. The References section should be organized in thefollowing numerical order:
1) For journals, include the following information: author names (up to threeauthors beginning with the first author; in case of more than threeauthors, et al. should be used), title, journal name (abbreviated), year of
publication, volume number, and page number (start-end pages).
・ Johnstone BM, Taylor KJ, Boyle AJ: Mechanics of the Guinea pig cochlea.
J Acoust Soc Am 1970; 47: 504-8.
・ Ferguson B, Matyszak MK, Esiri MM et al: Axonal damage in acutemultiple sclerosis. Brain 1997; 120: 393-9.
2) For books, include the following information: author, title, editor, booktitle, editorial version, publisher’s address and name, year of publication,and page numbers (start-end pages).
・ Mostofi FK: Benign hyperplasia of the prostate gland. In Campbell MF,
Harrison JH (Eds), Urology (3rd ed), Philadelphia, WB Saunders, 1970;
1065-129.
3) Provide the URL and date of access when citing materials or informationfrom the Internet.
・ The Ministr y of Health, Labour and Welfare: Basic Plan to Promote
Cancer Control Programs, http://www.mhlw.go.jp/bunya/kenkou/dl/
gan_keikaku02.pdf (accessed on July 1, 2016).
4) Use the same abbreviations for names of cited journals as MEDLINE or
Index Medicus.
5) If available, the electronic publication (Epub) date and DOI should belisted for online journals (Epub format only) and early publications (Epubahead of print).
6) In principle, special repor ts, manuscripts under submission, private
letters, and other materials that are not commonly available should not becited as references.
11.Figures: Select the size for publication, 8 cm or 17 cm in width.
12.The Editorial Board decides acceptance or rejection of the manuscript, as
well as the order of publication of manuscripts.
13.The manuscripts were proofread by the authors in both the first proof andthe reprint. Significant changes are not permitted during the proofreading.
The authors must keep the deadlines of the proofreading.
14.Any contents of the manuscript must not have been published in any otherjournals. It is also forbidden to make two or more submissions at the sametime. The following is an exception. Only when a paper was originallypublished in Japanese in this Journal does the Editorial Board expressly
approve secondary publication in English in other journals.
15.No charge for publication, up to ten pages of the general reviews, up to eightpages of the original ar ticles, and up to five pages of the case or shor treports. The cost of extra pages and reprints is the responsibility of theauthors. For invited manuscripts, there is no additional page charge. The
expense of color photographs should be borne by the authors.
16.Submission: To the address below, send one paper copy of the manuscript,
the manuscript’s electronic data, the application form for submission, thechecklist, the written oath, and the self-report of conflict of interest. Once themanuscript has been accepted, the final electronic data (including figures,tables, and photographs) must be submitted.
17.The copyrights to works published in this journal belong to the Medical
Society of Kanazawa Medical University.
Send submissions to: Editorial Board, Journal of Kanazawa Medical University
1-1 Daigaku, Uchinada, Kahoku, Ishikawa 920-0293, Japan
E-mail: hrc-jimu@kanazawa-med.ac.jp
These guidelines were partially revised in March, 2022.

金沢医科大学雑誌
第 48 巻 第 2 号

2023 年 12 月

目

次

総

説
Biodegradable Semi-Rigid Mitral Valve Annuloplasty Ring Designed for Children ……………………… 65
Makoto Ando, Takako Nishino

原著
Characteristic Clinical Features of Orthognathic Surgery Patients Encountered
Over 18year Period–a Retrospective Study ……………………………………………………………… 70
Miho Hasumoto, Taichi Demura, Hiroyuki Nakano, Yota Yamauchi,
Takao Kato, Eiji Mitate, Satoshi Wada, Noboru Demura
Stability Following Intraoral Vertico-Sagittal Ramus Osteotomy and Sagittal Split Ramus Osteotomy
for Asymmetric Mandibular Prognathism ………………………………………………………………… 76
Miho Hasumoto, Taichi Demura, Satoshi Wada, Yota Yamauchi,
Takao Kato, Eiji Mitate, Hiroyuki Nakano, Noboru Demura
Survey of the Review Process for Approved Animal Protocols and Feedback
to Education and Training ………………………………………………………………………………… 81
Shintaro Matsuba, Ryoya Yamamoto, Yasuhito Ishigaki,
Hirofumi Nishizono

症

例 報 告
Clinical Images: Megakaryocytic Emperipolesis in a Patient with Myelodysplastic Syndrome ………… 85
Naoki Okada, Reiko Fujisawa, Yutaka Saikawa, Hitoshi Sato

金沢医科大学医学会記録…………………………………………………………………………………… 87
第 49 回医学会総会・第 58 回学術集会
金沢医科大学医学会 2023 年度（第 29 回）
「論文表彰」 募集要項 ………………………………………… 90
		
受賞者一覧 ……………………………………… 91

編

集

金沢医科大学医学会

編集委員

西野 善一（委員長），清川 悦子（副委員長），朝比奈正人，岩脇 隆夫，
櫻井勝，高村 博之，林康彦，古市 賢吾，正木 康史，
山田 壮亮，米倉 秀人

J Kanazawa Med Univ 48：65 −69, 2023

Biodegradable Semi-Rigid Mitral Valve Annuloplasty Ring Designed for Children
Makoto Ando 1, 2)*, Takako Nishino 1, 2)
1)
2)

Department of Pediatric Surgery, Kanazawa Medical University
Department of Pediatric Cardiovascular Surgery, Kanazawa Medical University Hospital

Abstract: Descriptive information has indicated unsatisfactory outcomes associated with mitral valve plasty
in the case of pediatric patients. Conversely, favorable outcomes have been consistently reported in adult cases,
primarily attributed to the feasibility of prosthetic annuloplasty rings. Due to this notable distinction, we aimed
to address the specific needs of small children by developing a semi-rigid annuloplasty ring for the mitralvalve, employing biodegradable polymers. The expectation is that this approach would involve the gradualdegradation and absorption of the developed semi-rigid annuloplasty ring, coinciding with the remodeling of
the mitral annulus. The inner support medium was crafted from sutures composed of a blend of poly L-lactic
acid and poly ɛ-caprolactone copolymer, mixed at a molar ratio of 3:1. Subsequently, this material was bundled
together and coiled around a saddle-shaped mold rod. Following heat processing, a reinforced saddle-shaped
rod with a diameter of 0.6mm was successfully created. The external cuff utilized a blade weaving techniquemade of polyglycolic acid, facilitating the smooth insertion of needles. A blade material was woven using
16 sets of polyglycolic acid sutures (size 50D), resulting in an internal diameter of 2mm and an area densityof 0.55mg/mm³. The internal rod was inserted within the polyglycolic acid blade, and both ends were
subjected to heat processing at a temperature of 230°C for 10 seconds to prevent fraying. This device holds thepotential to offer a solution for enhancing the outcomes of pediatric mitral valve plasty, and address the current
challenges associated with unsatisfactory results in this patient population. Additionally, its applicability
to adult patients could potentially eliminate the requirement for lifelong anticoagulation therapy.
Key Words: mitral valve, annuloplasty ring, biodegradable polymer, children

Introduction
The objective of mitral valve plasty (MVP) is to ensure
lifelong prevention of regurgitation. MVP in children isestimated to be performed in approximately 300 cases
annually nationwide in Japan. Descriptive information,
however, unveiled unsatisfactory outcomes associatedwith pediatric MVP (1). Conversely, outstanding
outcomes have been documented in adult cases, primarily
attributed to the feasibility of prosthetic annuloplasty
rings (AR) (2). AR restores the physiologic saddleshape and normal size of the annulus, representing afundamental principle of MVP in adults. Nevertheless,commercially available AR are frequently oversized foruse
in growing
children.
1)Kohzaburo
Fujikawa-Yamamoto
Division of Cell Medicine, Research Institute of Medical Science,
Kanazawa Medical
University,
920-0293,* Departmentof PediatricSurgery,Uchinada,
KanazawaIshikawa
Medical University,
Japan
1-1
Daigaku, Uchinada, Kahoku, Ishikawa 920-0293, Japan
Corresponding
author:Kohzaburo
Fujikawa-Yamamoto
Tel: +81-76-286-2211,
Email: shannon@kanazawa-med.ac.jp
Accepted:
Accepted:November
December30,
13,2006
2023

AR have rigid, flexible, or semi-rigid variations.
Specifically, the semi-rigid AR demonstrates notableefficacy in restoring a saddle-shaped annulus. Typically,
it consists of an inner metal component, such as stainlesssteel or titanium, encased in fabric to provide a cuff forsutures. While materials like titanium exhibit strength,
lightness, and corrosion resistance, it is important to notethat titanium does not possess the ability to grow in size.
Hence, even if a smaller-sized annuloplasty ring could
be produced using a metal, it would impede annular
growth and necessitate a second surgery for retrieval.
On the other hand, if AR were manufactured using
biodegradable polymers (BDP), they could potentiallyensure both long-term prevention of regurgitation andstenosis. In the field of orthopedics, BDP have alreadybeen employed as an alternative to titanium as a material
for implants. Following this concept, we tried to develop
a semi-rigid AR for the mitral valve in small children,
utilizing BDP. The expectation is that the semi-rigid AR
made from BDP would undergo gradual degradation and65		

Ando/Nishino

Table 1. Brief overview of the differences between Poly L-lactic acid, poly ɛ-caprolactone, and polyglycolic acid.

PGA

PLLA

PCL

SourceSynthetic (petrochemicals)

Natural and synthetic (corn starch)

Synthetic (petrochemicals)

Mechanical Proper ties

High strength but can be brittle

High strength and stif fness

Flexible with a lower module than PLLA

Degradation Rate

Rapid degradation

Slow degradation

Slow degradation (slower than PLLA)

Applications

Sutures, tissue scaf folds

Medical implants, sutures, devices

Drug deliver y, tissue engineering

Biocompatibilitye

Generally biocompatible

Generally biocompatible

Generally biocompatible

PGA, Polyglycolic acid; PLLA, Poly L-lact ic acid; PCL, Polu ε-caprolact one

absorption while facilitating remodeling of the mitralannulus. This approach aims to prevent the developmentof stenosis over time. In this article, we conducted aliterature review using the medical literature referencesite PubMed to systematically explore potential BDP
suitable for AR, and to examine the mechanical anddegradation characteristics of these BDPs. Additionally,
we detail the construction method of our newly developed
AR specifically designed for children.
Potential BDPs to be used for AR
Recently, BDP have gained widespread use in the
manufacturing of biomedical devices. They have been
demonstrated to possess favorable biocompatibility,
controlled degradability, excellent processability, andappropriate mechanical strengths. Advancements infabrication techniques have enabled the swift constructionof scaffolds using various BDPs, with the added
advantage of not being restricted by specific shapes (3).
Commonly used BDP are mainly alpha-hydroxy acids
such as poly glycolic acid (PGA), poly lactic acid
(PLA), poly ɛ-caprolactone (PCL), polydioxanone,
polyhydroxylbutyratevalerate, polyacetyglutamic acid,polyorthoesters, polyethylene oxide, polybutylene
terephthalate, and others. Among these, sutures made of
PGA were the pioneering clinical devices crafted from
BDP, appearing in the market during the 1970s. Several
decades following the first PGA sutures, technologicaladvancements have evolved, allowing for thecustomization of BDP to fulfill specific requirements for
emerging fields, notably in the development of tissueengineered products. Throughout these advancements,
PLA, PGA, and PCL continue to be the cornerstone ofsynthetic BDP used in the fabrication of clinical products(4). PLA is a chiral molecule which exists in two
enantiomeric forms: L-lactic acid (PLLA) and D-lactic
acids (PDLA). PLLA is predominantly crystalline
and therefore could be a substrate for medical
devices, as opposed to PDLA which is chiefly
amorphous. These polymers are appealing due to theiroutstanding biocompatibility, degradability, andversatile physiochemical and mechanical properties.
66

These are the reasons PLLA have been extensively usedin the field of orthopedic, dermatological (5), andcardiovascular medicines encompassing biodegradable
stents (6). A brief overview of the differences between
PGA, PLLA, and PCL is listed on table 1.
Degradation rate of BDP
The strategic arrangement of various polymers, aimed
at regulating biodegradation time, holds particularsignificance in facilitating the normal growth of themitral valve annulus. The degradation rate of BDP is
primarily influenced by their hydrophilicity. For example,
PLLA is relatively hydrophobic, and thus is highly
biostable. In the in vivo study, the geometrical shapeand original height of the PLLA cage were preserved
throughout the six-month follow-up period. The
mechanical strength was also maintained for a period of
six months in vitro. At 12 months, the PLLA cage had
been disintegrated into multiple fragments with signs ofabsorption (7). This is in contrast to PGA, which, being
less hydrophobic, undergoes faster degradation within 512 months compared to PLLA, despite the latter’s higher
crystallinity (8, 9). PCL is a semi-crystalline material,
initiating degradation primarily in the amorphous
regions, while the crystalline regions remain intact for amore extended period. This characteristic contributes tothe prolonged maintenance of mechanical properties.
Following the degradation of the amorphous segments,
the cellular activity proceeds to degrade the crystalline
regions, leading to fragmentation and a subsequent
decrease in mechanical properties. Depending on its
molecular weight, PCL as a homopolymer exhibits
degradation times ranging from 2-4 years. Due to its
slow rate of degradation, PCL is well-suited for use inlong-term implantable devices (8).
The strength of BDP
BDP changes their shape by different temperature. It
starts melting above the melting temperature (Tm). Below
the glass transition temperature (Tg), the polymer chain
assumes a more rigid, glassy state, contributing to thematerial’s plasticity. Tg is proportional to the stiffnessof the polymer chain: the softer the polymer chain, theBiodegradable pediatric annuloplasty ring

lower the Tg. The Tm and Tg of PLLA are about 70 and
67 degrees, respectively. The strength of a polymer ischaracterized by the collective resistance from bothinternal and external molecular interactions against
external forces, leading to the initiation of moleculardisplacement. Generally, higher interaction forces
correlate with a higher Young’s modulus, which isrepresented by the slope of the initial linear elastic
deformation in the stress-strain curve. The tensile
strength for PLLA is reported to be 11.4 to 72 MPa, while
flexural strengths were 45 to 145 MPa. The initial
tensile strength and modulus are reported to be 60.3
MPa and 3.7 GPa. The Tm and Tg of PGA is reported to
be 225-230°C and 35-40°C, resulting in a high tensile
modulus. The strength of PGA and PLLA, therefore,
could be comparable with that of pure titanium, whose
Young’s modulus of elasticity is about 100GPa (10).
On the other hand, PCL has a low tensile strength
ranging between 10 and 27 MPa, but an extremely highelongation at breakage (>700%) (11). It is a semicrystalline polyester and properties of low Tg (-60°C),
low Tm (56-65°C), and high thermal stability (12).
Blending of BDP (Copolymerization)
Both PLLA and PCL have the capability to copolymerizewith other monomers or blend with additional polymers,
allowing for the enhancement of certain material
properties. In particular, composites involving PCL
blended with other polymers have found wide applicationin various settings, notably in tissue engineering, owing
to the material’s processability that facilitates the creationof diverse scaffold architectures (13), and has been used
for many biomaterials (14). It offers an advantage in theconstruction of implants with specific shapes through the
3-dimensional melt-plotting technique, primarily due to
its thermal stability in the molten state (12), possessing
porous structure which allows cell anchoring andvascularization (15). Furthermore, its mechanicalproperties are recognized to be modifiable through theincorporation of other biodegradable fibers. Particularly,
there have been thorough investigations into thesynthesis and degradation behavior of the copolymer
composed of PLLA and PCL. Blending PCL with PLLAis acknowledged to enhance the fracture strength of PCL(16). In the study, the tensile strength of PCL wasreported to be 19.3 MPa. Additionally, the tensile
strengths of copolymers consisting of 50%, 75%, 85%,
and 95% PLLA were measured at 0.6, 19.0, 22.1, and47.6 MPa, respectively (17). Conversely, blending with
PCL is recognized to enhance the flexibility of PLLA
(18). Moreover, this copolymer demonstrated an
accelerated degradation rate when contrasted with the
PCL homopolymer. Research has shown that initially,
PLLA segments undergo degradation, leaving behindsegments of PCL. This phenomenon results in PCL
maintaining its structural integrity for a prolonged

period (19). The PLLA-PCL copolymer, akin to the PCL
homopolymer, has demonstrated the ability to form 3dimensional structures without restrictions in shape.
Furthermore, its surfaces exhibit decreased platelet
adhesion and an enhanced proliferation of fibroblast
cells (20).
Design of the biodegradable ring (Figure 1-3)
Based on the insights discussed above, we endeavoredto fabricate an AR replicating the configuration ofcommercially available counterparts. This involved
utilizing 3 commonly employed biodegradable polymers:
PGA, PLLA, and PCA. Concerning the inner support
medium, a copolymer of PCA and PLLA was selected.
This choice was motivated by the fact that using PLLA
as a homopolymer would not confer the flexibility

Figure 1. Diagram illustrating the ring configuration: The inner support
medium is composed of a copolymer of poly ε-caprolactone and L-poly
lactic acid. The external cuff is a blade material woven with 16 sets ofpolyglycolic acid sutures.

Figure 2. Image of annuloplasty rings featuring various sizes, dyed withtwo colors. The orange segment has undergone heat processing to prevent
fraying and does not contain an inner support medium. This section is
pliable, potentially efficient in preventing erosion to the aortic tissue,and can be trimmed if redundant. The purple segment contains the inner
support medium.

Figure 3. Image of an annuloplasty ring showcasing a certain degree of
flexibility.

67

		

comparable to metals like titanium. Hence, our objective
was to copolymerize PLLA with PCL, the softer material,
to attain a balance of flexibility, sufficient strength,
and suitability for tissue ingrowth. Drawing from thepreceding discussions, we extrapolated that the assumed
absorption rate of the PLLA-PCL copolymer should
extend beyond 6 months. This duration is deemedsufficient to ensure the remodeling of the valve annulus.
We hypothesized that a favorable mean molecular weightof the copolymer should be within the range of 200 to
800kDa. We also hypothesized that the size of thereinforcing rod should be within the range of 0.3 to 0.8
mm. Based on these assumptions, we decided to employ
3 sutures sized #2 (as per the United States Pharmacopeia
standards). These sutures were crafted from a PLLA/PCL copolymer blend at a molar ratio of 3:1. The
aforementioned sutures were bundled together and coiled
around the saddle-shaped mold rod. Following heatprocessing at a temperature of 120°C for 3 hours, areinforced saddle-shaped rod with a diameter of 0.6mm
was successfully produced. For the external cuff, weemployed the blade weaving technique—a distinctive
method to produce a soft and bulky suture material craftedfrom PGA. This choice was made to facilitate smoothneedle insertion. As discussed earlier, it is known thatPGA degrades at a faster rate compared to the PLLA/PCL copolymer. We believe that the complete absorptionof the outer cuff should precede that of the inner rod. Thissequencing is deemed necessary to prevent irregular scarformation around the ring. A blade material weavedwith 16 sets of PGA sutures (size 50D), resulted in aninternal diameter of 2mm and area density of 0.55mg/
mm3. The internal rod was placed inside the PGA blade,and both ends were heat processed at a temperature of
230 C° for 10 seconds to prevent fraying.
Utilizing this AR, we initiated an in vitro experimentemploying the following method. Initially, we detached
the porcine mitral valve with attached chordae tendineae
and papillary muscles, installing it in a simulator tankto create an explanted heart test model. Subsequently,
we elongated the posterior leaflet in the longitudinal
direction, resulting in the development of a mitral valve
regurgitation model with an approximate regurgitation
fraction of 40% when integrated into a pulsatile circuit.
Through the application of the present AR, we conducted
MVP and identified the device’s effectiveness throughthe reduction of the regurgitation fraction.
Future prospect of the clinical use
The mechanical properties and degradation rate of thisAR should be assessed using animal models, followed bynecessary modifications based on the observed outcomes.
Extrapolating from the data on PGA, PLLA, and PCL,
it is anticipated that the present AR will undergo
absorption over a period ranging from 6 months toseveral years. The adequacy of this time period to ensure
68

Ando/Nishino

remodeling of the annulus remains uncertain due to theabsence of objective data from MVP cases in growing
children. Nevertheless, it is worth noting that this AR
should not impede the growth of the annulus, given its
expected absorption within several years. Moreover,an ideal biodegradable artificial ring should exhibit
mechanical properties, including radio force, that arecomparable to those of a metal ring. For example,
flexibility range of titanium is 7.6mm and 2.4mm in the
septal-to-lateral and commissure-to-commissure direction
in a size 32 Physio I Annuloplasty ring (Edwardes
Lifesciences, Irvine, CA, USA.) (21). This flexibility
is particularly crucial for stress adaptation, helping to
mitigate the risk of ring dehiscence. On the other hand,the elastic modulus of BDP materials can differ from thatof metals. For instance, there is a report indicating thata PLLA composite possesses a flexural modulus that is
62% of that found in stainless steel (22).
Hence, additional adjustments to the mechanochemical
characteristics of the AR may be necessary. For instance,
the degradation rate of BDP can be altered by adjusting
their size and shape (23), and the strength loss during a
specific period is often considered to be proportional
to the diameter of the material (24). Also, the strengthof BDP can be modified through various methods
beyond copolymerization. For example, polymers can be
reinforced by incorporating other fibers, such as carbon
or calcium phosphate. Also, the reinforcing fiber canbe the same polymer itself (self-reinforcement) (25).
Finally, the potential for an inflammatory reaction
to the product is a crucial concern, as it could lead totissue overgrowth and scar formation. This, in turn, has
the potential to fix the annulus and result in stenosis
or clot formation. Clinical experience with devices
implanted inside the cardiovascular system has been
primarily focused on biodegradable stents (26, 27).
Prototypes of biodegradable stents were produced from
PLLA. The mixed results in inflammatory response andendothelial hyperplasia observed in both in vivo andin vitro studies highlight the complexity of evaluating
the performance of biodegradable stents (28-31).
Nevertheless, elucidating the absence of inflammationand tissue proliferation is crucial in ensuring the safety
and efficacy of the present AR. Conducting a series ofin vitro mechanical studies and in vivo microscopic
evaluations is also essential for thoroughly assessing theperformance and biocompatibility of this AR. While
there are challenges to address before clinical use, thedevelopment of a biodegradable AR holds promise asa potential solution to enhance outcomes in pediatricMVP. In addition, the potential for eliminating the needfor lifelong anticoagulation therapy with the use of thisAR could offer significant advantages, not only in thepediatric population but also in adult patients.

Biodegradable pediatric annuloplasty ring

Conflict of Interest
The annuloplasty ring presented in this paper was
manufactured by Gunze Ltd. (Ayabe, Kyoto, Japan).
The first author is the advisor for the product, but there
is no conflict of interest for the author, and the work is
not funded by the company.
Declaration of Generative AI and AI-assisted
technologies in the writing process
During the preparation of this work, the authors
employed the assistance of the AT tool ChatGPT toenhance language and ensure grammatical accuracy.
Subsequently, the authors thoroughly reviewed and edited
the content as necessary, assuming full responsibility
for the publication’s substance.
Abbreviations
AR, Annuloplasty ring; BDP, biodegradable Polymer;
MVP, Mitral valve plasty; PCL, Poly ε-caprolactone;
PGA, Polyglycolic acid; PLLA, Poly L-lactic acid; Tg,
glass-transition temperature; Tm, melting temperature
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poly-l-lactic acid coronary stents in humans. Circulation 2000; 102: 399-404.
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J Kanazawa Med Univ

48：70 −75, 2023

Characteristic Clinical Features of Orthognathic Surgery Patients Encountered
Over 18year Period–a Retrospective Study
Miho Hasumoto, Taichi Demura, Hiroyuki Nakano*, Yota Yamauchi,
Takao Kato, Eiji Mitate, Satoshi Wada, Noboru Demura
Department of Oral and Maxillofacial Surgery, Kanazawa Medical University

Abstract: Background: Since surgical orthodontic treatment for jaw deformity became covered by
Japanese health insurance in 1996, the economic burdens associated with treatment have been reduced
and social recognition has increased. The number of patients attending hospital for surgical orthodontic
treatment has thus been increasing yearly. This study aimed to survey the characteristics of orthognathic
surgery performed at Kanazawa Medical University Hospital.
Method: This retrospective investigation analyzed the medical records of patients with well-documented
orthognathic surgery treated in the Department of Oral and Maxillofacial Surgery at Kanazawa Medical
University Hospital during the 18-year period from January 2004 to December 2021. Patient records andradiographs were used to obtain sex, age, diagnosis, and surgical technique data.
Results: A clinical study was conducted on 113 patients who underwent orthognathic surgery between
January 2004 and December 2021. Skeletal prognathism with asymmetry was the most common clinicaldiagnosis (40 cases), followed by skeletal prognathism alone (39 cases). In surgical procedures, sagittal
split ramus osteotomy was the most common surgical procedure (40 cases), followed by bimaxillaryosteotomy (34 cases). For the maxilla, Le Fort 1 osteotomy was performed in most cases. Conversely,
several surgical procedures were performed for the mandible. The proportion of bimaxillary surgeries wasincreasing in 2021.
Conclusions: Recent increases in complicated procedures may signify improvements in surgical
techniques and perioperative management.
Key Words: orthognathic surgery, jaw deformity, retrospective study

Introduction
Since surgical orthodontic treatment for jaw deformity
became covered by Japanese health insurance in 1996,
the economic burdens associated with treatment havebeen reduced and social recognition has increased. As
a result, the number of patients attending hospital for
surgical orthodontic treatment has been increasing yearly.
Several surgical orthodontic techniques are used, withvarious advantages and disadvantages being reported for*1)Kohzaburo
DepartmentFujikawa-Yamamotoof Oral and Maxillofacial Surgery, Kanazawa
Division University,of Cell Medicine,Research
Institute ofMedicalIshikawa
Science,
Medical1-1 Daigaku,
Uchinada,
Kahoku,Kanazawa
Medical University, 1-1 Daigaku, Uchinada,920-0293,
Japan
Ishikawa
920-0293, Japan
Tel: +81-76-286-2211,
Fax: +81-76-286-2010
Corresponding
author: Kohzaburo Fujikawa-Yamamoto
Email: nakano-h@kanazawa-med.ac.jp
Accepted:
Accepted:November
November30,
29,2006
2023
70

each. According to reports in Japan, Le Fort 1 osteotomy
is mostly performed for the maxilla. On the other hand,several surgical procedures are performed for themandible.
The aim of this retrospective study was to survey
the characteristics of surgical orthodontic treatment incases treated at our institution.

Methods
This retrospective investigation analyzed the medical
records of patients with well-documented orthognathic
surgery treated in the Department of Oral andMaxillofacial Surgery at Kanazawa Medical University
Hospital during the 18-year period from January 2004 to
December 2021. The inclusion criteria were: subjects
who underwent orthognathic surgery; and availabilityof comprehensive medical records and radiologicalCharacteristic clinical features of orthognathic surgery patients

investigations. Patient records and radiographs were used
to obtain the following information: sex; age; diagnosis;
surgical technique.
The Research Ethics Committee of Kanazawa
Medical University Hospital approved this study(protocol no. 1720).
Results

1. Patients
A total of 113 patients were surveyed, comprising 35
males and 78 females. The male-to-female ratio wasapproximately 1:2.2 (Fig. 1). Overall, age ranged from15 to 52 years, with a mean of 23.7 years for all patients,
24.5 years for males and 23.4 years for females. Modal
age was 20 years for males and 17 years for females(Fig. 2).
2. Clinical diagnosis
Skeletal mandibular protrusion with asymmetry was themost common clinical diagnosis with 40 cases, followedby skeletal mandibular protrusion alone in 39 cases andskeletal mandibular protrusion with open bite in 10 cases.
Five cases showed skeletal mandibular protrusion withasymmetry and open bite (Table 1).

3. Surgical technique
Surgery was sagittal split ramus osteotomy (SSRO) alone
in 40 cases, combined SSRO and Le Fort 1 osteotomy in
24 cases, and intraoral verticosagittal ramus osteotomy(IVSRO) in 18 cases. Recently, the proportion of cases ofbimaxillary osteotomy has increased (Table 2, Fig. 3, 4).
The osteotomy line of SSRO, intraoral vertical ramus
osteotomy (IVRO) and IVSRO were shown in Fig 5.

Discussion
Mean patient age was 23.7 years, with a mode of 20
years for males and 17 years for females. Mean age at
the time of surgery was similar to previous reports (1, 2).
This was attributed to the fact that surgery was performed
after growth of the jawbone was completed and thatmany patients wished to have the surgery before entering
university. Other institutions have reported mandibular
protrusion alone as the most common clinical diagnosis(3, 4). On the other hand, almost half of all survey
subjects (48.6%) showed asymmetry in a report by Oguri
et al. (5). Skeletal mandibular protrusion with asymmetry
was the most common underlying pathology in our
department and the proportion of cases with mandibular
protrusion was 83.1%, making this exceedingly common
in our department. Our results were similar to thosereported from other institutions (1, 4).

Fig. 1. Number of patients with jaw deformity in each year
A total of 113 patients were surveyed, comprising 35 males and 78 females. The male-to-female ratio was approximately 1:2.2.

71

		

Hasumoto/Demura/et al.

Fig. 2. Age distribution of patients at operation
Overall, age ranged from 15 to 52 years, with a mean of 23.7 years for all patients, 24.5 years for males and 23.4 years for females. Modal age was 20
years for males and 17 years for females.

Table 1. Distribution of diagnoses for patients who underwent orthognathic surgery

72

Clinical diagnosis

Number of patients

Ratio (%)

Mandibular protrusion

39

34.5

Mandibular protrusion + Asymmetry

40

35.4

Mandibular protrusion + Open bite

10

8.8

Mandibular protrusion + Asymmetry + Open bite

5

4.4

Maxillary protrusion

2

1.8

Maxillary protrusion + Asymmetry

1

0.9

Maxillary protrusion + Open bite

6

5.3

Maxillary protrusion + Asymmetry + Open bite2

1.8

Asymmetry

7

6.2

Open bite

1

0.9

Characteristic clinical features of orthognathic surgery patients
Table 2. Distribution of surgical procedures

Surgical procedures
LFI + SSROLFI + SSRO + Genioplasty
LFI + SSRO + IVROLFI + IVSROLFI + SSRO + IVSRO + Resection of mandibular inferior marginal bone
LFI + Distraction osteogenesis of mandible
Anterior segmental osteotomy of Maxilla + SSRO + Genioplasty
LFI
SSRO
SSRO + Genioplasty
SSRO + IVSROSSRO + IVROIVSROIVSRO + Genioplasty
IVSRO + IVRO
IVRO
Genioplasty

Number of patients
24
3
2
2
1
1
1
1
40
9
1
3
18
3
1
2
1

LFI: Le Fort I osteotomy; SSRO: sagittal split ramus osteotomy; IVRO: intraoral vertical ramus osteotomy;
IVSRO: intraoral verticosagittal ramus osteotomy.

Fig. 3. Changes in distribution of surgical procedures
Surgery was sagittal split ramus osteotomy (SSRO) alone in 40 cases, combined SSRO and Le Fort 1 osteotomy in 24 cases, and intraoral vertical ramus
osteotomy (IVRO) in 18 cases.

73

		

Hasumoto/Demura/et al.

Fig. 4. Change in distribution of mandibular surgical procedures
Sagittal split ramus osteotomy (SSRO) was increased from 2014, intraoral verticosagittal ramus osteotomy (IVSRO) has not performed since 2016.

Fig. 5. Cutting lines of mandibular surgical procedures
The osteotomy line of sagittal split ramus osteotomy (SSRO) set toconnect the buccal osteotomy line and lingual osteotomy line, and theosteotomy line of intraoral vertical ramus osteotomy (IVRO) set posterior
on lingula of mandible. The osteotomy line of intra verticosagittal ramus
osteotomy (IVSRO) set to combinate the two osteotomy line.

74

Orthognathic surgery is now widely practiced andis considered an important specialty of oral andmaxillofacial surgery. Procedures are currently
performed to improve jaw function, including occlusion,in patients from their teens to 60s. Collaboration not onlywith oral and maxillofacial surgeons and orthodontists,
but also with prosthodontists and conservative dentists istherefore essential. A nationwide survey of orthognathic
treatment in Japan determined that SSRO comprised
approximately 70% of orthognathic surgeries (6).
Similarly in the present study, the surgical technique
was SSRO in 40 cases, making this the most common
surgery in our department. On the other hand, IVSRO
was often selected in our department, from 2004 to
2013. In 1992, Choung introduced IVSRO to combine
the advantages of both SSRO and IVRO (Fig. 4).
Theoretically, IVSRO was developed to avoid
displacement of the condyle by making an osteotomy
plane that is parallel to the original sagittal plane. To
make this parallel plane, the osteotomy plane is made in
the posterior part of the mandibular ramus, from justanterior to the antilingular prominence to the medial
posterior border of the mandibular ramus. IVSRO thus
has the advantage of minimizing the adverse effects on
the temporomandibular joint due to rotation of thelong axis of the mandibular condyle within the
glenoid or medial-lateral deviation of the condyleitself (7-9). In other words, IVSRO has a wider range

Characteristic clinical features of orthognathic surgery patientsof indications than IVRO and is effective for patientswith temporomandibular joint symptoms (7), and was
actively indicated for patients with temporomandibular
joint dysfunction. However, the number of IVSRO has
decreased since 2014. A survey in Japan reported thatthe number of facilities choosing IVRO was decreasedin the 2017 survey compared to the 2006 survey (6).
This decrease has been attributed to the postoperative
instability of the jaw position and the prolongation of
postoperative intermaxillary fixation and traction(10). IVSRO may cause serious complications if not
performed appropriately (11) and, like IVRO, thepostoperative period of jaw positioning andintermaxillary fixation/traction are prolonged. The
number of cases selected was therefore thought tohave decreased in the same way. We believe that one
reason for this is the increased esthetic demands ofpatients and the fact that the surgical plan was madewith consideration given to postoperative stability andthe airway. In addition, improvements in the precisionof surgical instruments and in the skills of surgeons
are also considered to have contributed to better
results and changes in surgical technique.
Conclusion
This study clarified recent changes to surgical techniquesin our department. In the future, the stability of thedifferent surgical techniques used in our department
will need to be examined.
None declared.

Conflict of interest

References
1. Suzuki T, Kawamoto T, Yamada D et al: Clinical statistical analysis oftreatment for jaw deformities in the Section of Maxillofacial Orthodontics,
Department of Orthodontics, Tokyo Medical and Dental University Dental
School Hospital. Jpn J Jaw Deform 2010; 20: 220-7. (in Japanese withEnglish abstract)
2. Yamamoto K, Kawakami M, Fujimoto M et al: Clinico-statistical analysis onor thognathic surgeries over 20 years at the Depar tment of Oral andMaxillofacial Surgery, Nara Medical University. Jpn J Jaw Deform 2003;
13: 27-34. (in Japanese with English abstract)
3. Hijioka H, Nozoe E, Shimomatsu K et al: Clinical outcome of patients withjaw deformity treated in our clinic during the past 24 years. Jpn J Jaw
Deform 2007; 17: 200-5. (in Japanese with English abstract)
4. Hanji K, Fujiwara T, Moriyama N et al: Investigation of jaw-deformity
patients over 10 years in the Department of Orthodontics, Aichi-gakuin
University Hospital. Jpn J Jaw Deform 2010; 20: 267-74. (in Japanese withEnglish abstract)
5. Oguri Y, Naganuma K, Harada F et al: Clinical survey of surgical-orthodontics
cases treated in the past decade at the Orthodontic Department, Niigata
University Medical and Dental Hospital. Jpn J Jaw Deform 2010; 20: 297-304.
(in Japanese with English abstract)
6. Kobayashi T, Saito C, Inoue N et al: Treatment of jaw deformity: a nationwide survey of the situation in Japan. Jpn J Jaw Deform 2008; 18: 237-50.
(in Japanese with English abstract)
7. Fujimura K, Segami N, Sato J et al: Advantages of intraoral verticosagittal
ramus osteotomy in skeletofacial deformity patients with temporomandibular
joint disorders. J Oral Maxillofac Surg 2004; 62: 1246-52.
8. Hashemi HM: Evaluation of intraoral verticosagittal ramus osteotomy forcorrection of mandibular prognathism. J Oral Maxillofac Surg 2008; 66:
509-12.
9. Lima SM, Granato R, Marin C et al: Analysis of 40 cases of intraoral
verticosagittal ramus osteotomy to treat dentofacial deformities. J Oral
Maxillofac Surg 2009; 67: 1840-3.
10. Katagiri W, Kobayashi T, Sasaki A et al: Investigation of surgical orthodontic
treatment in Japan -a nation survey by Japanese Society for Jaw Deformities in2017-. Jpn J Jaw Deform 2020; 30: 213-25. (in Japanese with English abstract)
11. Fujimura K, Segami N, Kobayashi S: Anatomical study of the complicationsof intraoral vertico-sagittal ramus osteotomy. J Oral Maxillofac Surg 2006;
64: 384-9.

75

J Kanazawa Med Univ

48：76 −80, 2023

Stability Following Intraoral Vertico-Sagittal Ramus Osteotomy and Sagittal Split
Ramus Osteotomy for Asymmetric Mandibular Prognathism
Miho Hasumoto, Taichi Demura, Satoshi Wada, Yota Yamauchi, Takao Kato,
Eiji Mitate, Hiroyuki Nakano*, Noboru Demura
Department of Oral and Maxillofacial Surgery, Kanazawa Medical University

Abstract: Objective: The purposes of this study were to clarify differences in skeletal stability and tocompare transverse and sagittal angulations of the proximal segment following correction of asymmetricmandibular prognathism using intraoral vertico-sagittal ramus osteotomy (IVSRO) and sagittal split
ramus osteotomy (SSRO) procedures.
Methods: Fifteen patients with mandibular protrusion and deviation were enrolled in this study, withIVSRO in seven and SSRO in eight. Lateral and posteroanterior cephalograms obtained before surgery(T0), within four weeks of surgery (T1), and at least 10 months after surgery (T2) were analyzed andangular measurements obtained at these time points were compared.
Results: No significant differences in vertical and horizontal movements of point B and the menton wereobserved between the IVSRO and SSRO groups. Intergonial width increased significantly from T0 to T1
in the IVSRO group.
Conclusions: IVSRO and SSRO conferred good postoperative stability when used to correct mandibular
protrusion and deviation. Although IVSRO led to an initial increase in intergonial width, this gradually
decreased within approximately 10 months after surgery.
Key Words: asymmetric mandibular prognathism, intraoral vertico-sagittal ramus osteotomy (IVSRO), sagittal split ramus
osteotomy (SSRO), stability

Introduction
Sagittal split ramus osteotomy (SSRO) is the mostfrequently used technique for treating mandibular
prognathism with deviation. The chief advantages of
SSRO are the optimal contact at the bony interface
between osteotomized segments and the ability to set backor advance the mandible according to the requirementsof the individual patient. On the other hand, theincidences of medial condylar displacement androtation of the long axis of the condylar segment arehigh with SSRO, because of the bony interference
between the proximal and distal segments in patientswith mandibular asymmetry (1-6).
*1)Kohzaburo
DepartmentFujikawa-Yamamotoof Oral and Maxillofacial Surgery, Kanazawa
Divisionof Cell Medicine,Research
Institute ofMedicalIshikawa
Science,
Medical University,
1-1 Daigaku,
Uchinada,
Kahoku,Kanazawa
Medical University, 1-1 Daigaku, Uchinada,920-0293,
Japan
Ishikawa
920-0293, Japan
Tel: +81-76-286-2211,
Fax: +81-76-286-2010
Corresponding
author: Kohzaburo Fujikawa-Yamamoto
Email: nakano-h@kanazawa-med.ac.jp
Accepted:
2006
Accepted:November
December30,
4, 202376

Intraoral vertico-sagittal ramus osteotomy (IVSRO)
was introduced by Choung in 1992 (7). The osteotomy
plane in this technique theoretically lies parallel to theoriginal sagittal plane, thus providing a larger contact
area between the proximal and distal segments after theprocedure than with intraoral vertical ramus osteotomy(IVRO). This maneuver helps adapt the IVSRO
procedure for mandibular advancement and upward
rotational movement. Moreover, IVSRO can be used forthe treatment of prognathism with excessive flaring of
the ramus and reduces the incidences of medial andlateral condylar displacement and rotation of the longaxis of the condylar segment (7, 8).
To the best of our knowledge, no studies have assessedskeletal stability and movement of the proximal segment
after correction of mandibular prognathism with deviationby comparing IVSRO with other surgical methods.
The purpose of this study was to compare skeletal
stability and proximal segment movement following
IVSRO and SSRO in patients with mandibular
prognathism with deviation.

Stability following IVSRO and SSRO

Methods

1. Patients
This retrospective study was reviewed and approvedby the institutional review board of Kanazawa Medical
University (approval no. I307). Participants consisted of
15 patients who had undergone orthognathic surgery at
Kanazawa Medical University Hospital, Japan, between
July 2001 and August 2015. The study population
comprised 15 women with asymmetric mandibular
prognathism treated using either IVSRO (seven patients;
mean age, 25.0±6.8 years) or SSRO (eight patients; meanage, 23.9±9.9 years). Osseous fixation was not used in
the IVSRO group, and maxillomandibular fixation(MMF) was performed for 17.9±4.3 days postoperatively.
Rigid fixation was used in the SSRO group (bicorticalscrews in seven patients, titanium miniplates on eachside in one patient), and MMF was maintained for 9.4±2.9 days postoperatively. The eligibility criteria forinclusion in this study were as follows: 1) presence ofmandibular prognathism; 2) clinically diagnosed
asymmetry of the lower face with mandibular midline
deviation of at least 4 mm at the menton (Me); 3)
absence of maxillary orthognathism; 4) absence ofcleft palate, craniofacial syndromes, or trauma; 5)availability of complete, good-quality records of lateraland posteroanterior (PA) cephalograms obtained presurgery (T0), within four weeks of surgery (T1), and at
least 10 months after surgery (T2); and 6) performanceof pre- and postoperative orthodontic treatment.
2. Surgical methods
The SSRO technique was performed in accordance withthe method described by Obwegeser’s. Rigid fixation wasused in the SSRO group (bicortical screws were inserted
in seven patients and bilateral titanium miniplates wereinserted in one patient). Straight IVSRO (Choung’s II
osteotomy) was performed as described previously by
Choung (7). Rigid fixation was not used in the IVSRO
group.
3. Measurement Methods
PA and lateral cephalograms were used to evaluate
post-surgical stability. Each participant underwent
cephalography at all three time points of T0, T1 and T2.
All cephalograms were traced on acetate paper andmeasurements were made manually. All tracings andmeasurements were conducted by the same researcher.
Linear and angular measurements obtained fromlateral cephalography in this study are illustrated in
Figure 1. An X-Y coordinate system was constructed
on tracings as follows: a line originating from thesella point, 6° downward from the sella-nasion line toapproximate the true horizontal axis was designated as
the X-axis; a perpendicular dropped to this line at the

Figure 1. Lateral cephalogram: landmarks, skeletal reference lines, and linear
measurements.
X-axis, a line originating from the sella point, 6° downward from the sellanasion line; Y-axis, a line dropped from the sella perpendicular to the X-axis;
point B (horizontal movement), distance between point B and the Y-axis;
point B (vertical movement), distance between point B and the X-axis;
ramus inclination, inclination between the mandibular ramus posteriorborder plane and the Frankfort plane.

sella marked the vertical Y-axis. Distances between point
B and the X-axis and between point B and the Y-axis
were used. Ramus inclination angle was measured as
the inclination between the posterior border plane andFrankfort plane of the mandibular ramus.
The lines and measurements obtained from PA
cephalograms in this study are illustrated in Figure 2. The
facial midline was at right angles to the latero-orbital (Lo)line and passed through the crista galli (Cg). Mandibular
deviation (MD) was measured as the distance between
the menton and facial midline. Inter-ramus width (IRW)
was measured as the distance between ramus posterior
points (RPs) on the right and left sides. Intergonial width(IGW) measures the distance between the gonion (Go) on
the right and left sides. The angulation of each proximal
segment relative to the upper orbital margin (Ro) line wasmeasured and the sum of the angles on the right and left
sides was designated as the total ramus angle (TRA).
77

		

Hasumoto/Demura/et al.

was -7.5±4.51 mm (p<0.05), -7.43±4.41 mm (p<0.05),
and 0.07±0.84 mm (p>0.05), from T0 to T1, T0 to T2,
and T1 to T2, respectively.
In the SSRO group, horizontal movement of point B
was -5.81±1.77 mm (p<0.05), -4.18±1.36 mm (p<0.01),
and 1.63±1.71 mm (p>0.05) from T0 to T1, T0 to T2,
and T1 to T2, respectively. No significant differencein the horizontal movement of point B was observed
between the IVSRO and SSRO groups during the entire
observation period.
2. Point B (Vertical Movement)
In the IVSRO group, vertical movement of point B was
0.21±3.65 mm (p>0.05), -0.43±4.34 mm (p>0.05), and-0.64±3.11 mm (p>0.05) from T0 to T1, T0 to T2, andT1 to T2, respectively.
In the SSRO group, vertical movement of point B
was -0.69±4.33 mm (p>0.05), -0.88±2.54 mm (p>0.05),
and -0.19±2.71 mm (p>0.05), from T0 to T1, T0 to T2,
and T1 to T2, respectively. No significant differences wereobserved in the vertical movement of point B between
the IVSRO and SSRO groups during the entire period.

Figure 2. Posteroanterior cephalogram: landmarks, skeletal reference lines,
and linear measurements.
Ro, roof of the orbit; Lo, intersection of the lateral orbital contour with theinnominate line; Rp, intersection of the mastoid process and lateral edge ofthe ramus of the mandible; Go, highest point in the antegonial notch of themandible; Me, menton; Cg, crista galli; Ro line, a line connecting left andright Ro points; Lo line, a line connecting left and right Lo points; Rp-Go
line, a line connecting the Rp point and Go points; FM line, a line
perpendicular to the Lo line through the crista galli (Cg); IRW, inter-ramus
width measured as the distance between ramus posterior points (Rp) on
the right and left sides; IGW, intergonial width measured as the distance
between the gonion (Go) on the right and left sides; RA, angle between
the Rp-Go line and Ro line; TRA, sum of RAs on the right and left sides;
MD, perpendicular distance from the FM line to the Me.

4. Statistical Analysis
Statistical analysis was performed using the Mann–
Whitney U test to compare the IVSRO and SSRO
groups. The Wilcoxon signed-rank test was used forcomparisons of values obtained at various time points inthe same surgical group. Differences were consideredsignificant at the level of p<0.05.
Results
Table 1 compares surgical and postoperative changes
between groups.
1. Point B (Horizontal Movement)
In the IVSRO group, horizontal movement of point B
78

3. IGW
IGW increased significantly from T0 to T1, thendecreased from T1 to T2 in the IVSRO group. No
significant difference in IGW was observed for theoverall observation period in the SSRO group. Significant
differences in IGW were observed between the IVSROand SSRO groups in the T0–T1 period.
4. IRW
No significant differences in IRW in the IVSRO groupwere identified at the different time points during theobservation period. IRW decreased significantly from
T1 to T2 in the SSRO group. No significant differencein IRW was noted between the IVSRO and SSRO
groups during the entire observation period.
5. MD
Significant differences in Me position were observed
between the T0–T1 and T0–T2 periods in the IVSRO
group. Significant differences in position of the Me wereobserved between the T0–T1 and T0–T2 periods in the
SSRO group. No significant difference was observed
during the entire observation period between the
IVSRO and SSRO groups.
6. TRA
TRA decreased significantly from T1 to T2 in the IVSRO
group. No significant difference was seen during the entire
observation period in the SSRO group. No significant
differences in TRA were observed between the IVSROand SSRO groups during the entire observation period.

Stability following IVSRO and SSRO
Table 1. Comparison of surgical and postoperative changes between groups.

Mean

SD

P value

MeanSD

P value

P valuebetweengroupsB point(Horizontal)(mm)
T0-T1
T0-T2
T1-T2

-7.5
-7.43
0.07

4.51
4.41
0.84

0.022 ＊
0.016 ＊
1

-5.81
-4.18
1.63

1.77
1.36
1.71

0.014 ＊
＜0.001 ＊＊
0.058

0.352
0.131
0.086

B point(Ver tical)(mm)
T0-T1
T0-T2
T1-T2

0.21
-0.43
-0.64

3.65
4.34
3.11

1
0.578
0.584

-0.69
-0.88
-0.19

4.33
2.54
2.71

0.674
0.394
0.672

0.602
0.815
1

IGW(mm)
T0-T1
T0-T2
T1-T2

5.14
0.43
-4.71

3.02
1.97
3.49

0.016 ＊
0.67
0.036 ＊

-0.38
0.18
0.56

1.75
2.47
4.15

0.547
1
0.944

0.003 ＊＊
1
0.063

IRW(mm)
T0-T1
T0-T2
T1-T2

2.07
-0.36
-2.43

2.59
2.39
2.57

0.128
0.671
0.1

-1.63
-3.32
-1.69

6.44
4.39
1.51

1
0.105
0.022 ＊

0.093
0.262
0.907

MD(mm)
T0-T1
T0-T2
T1-T2

5
3.93
-0.93

1.5
1.84
0.98

0.022 ＊
0.016 ＊
0.203

4.81
4.81
0

2.74
2.6
2.43

0.02 ＊
0.014 ＊
0.916

0.953
0.417
0.412

TRA(degrees)
T0-T1
T0-T2
T1-T2

3.36
0.14
-3.21

5.6
3.03
3.88

0.149
0.832
0.022 ＊

2.69
2
-0.69

3.79
4.64
3.41

0.089
0.362
0.553

0.862
0.639
0.449

Ramus inclination(degrees)
7
T0-T1
3.5
T0-T2
-3.64
T1-T2

4.44
4.2
3.06

0.034
0.128
0.016 ＊

6.81
4.06
-2.75

1.75
4.11
3.67

0.014 ＊
0.106
0.108

0.415
0.954
0.772

IVSRO(n=7)

SSRO(n=8)

IVSRO, intraoral verticosagittal ramus osteotomy; SSRO, sagittal split ramus osteotomy; SD, standard deviation.
*p<0.05, **p<0.01

7. Ramus Inclination
Ramus inclination increased significantly from T0 to
T1 and decreased significantly from T1 to T2 in the
IVSRO group. In the SSRO group, ramus inclination
increased significantly from T0 to T1. No significant
difference in ramus inclination was identified between the
IVSRO and SSRO groups during the entire observation
period.
Discussion
The purpose of this study was to clarify differences inskeletal stability and to compare transverse and sagittal
angulations of the proximal segment after the correctionof asymmetric mandibular prognathism via IVSRO and

SSRO procedures. We found no significant differencesin specific postoperative stability in the horizontal orvertical planes after IVSRO or SSRO.
Hashemi reported that mean horizontal relapse atpoint B was 2.16 mm for mandibular setback withbilateral IVSRO under rigid fixation (9). Previous studies
have reported the mean horizontal relapse at point B
for mandibular setback with bilateral SSRO with rigid
fixation as 0.74±2.0 mm (10) and 1.59±3.62 mm (11).
In our study, mean horizontal relapse at point B was
0.07±0.84 mm for IVSRO without rigid fixation and
1.63±1.71 mm for SSRO with rigid fixation.
Al-Moraissi et al. reported greater vertical stability
in the SSRO group than in the IVRO group (12). The
79

		

present study found no significant difference in verticalstability between the IVSRO and SSRO groups,
suggesting that the IVSRO procedure provides adaquate
vertical stability. However, further studies are required
to clarify vertical stability after IVSRO in a larger cohort
with longer follow-up. IVSRO was developed as amethod to address the problems inherent in SSRO and
IVRO. The osteotomy plane in this technique, which
theoretically lies parallel to the original sagittal plane,
provides a larger contact area between the proximaland distal segments after the operation than seen with
IVRO. The operation methods can reduce the incidencesof medial and lateral condylar displacement or rotationof the long axis of the condyle segment. Bayat et al.
investigated transverse displacement and angulation of
the proximal segment after IVSRO and found that IGW,
IRW, and ramus angles all increased postoperatively(13). Our study found that IGW increased significantly
from T0 to T1, then decreased significantly from T1
to T2 in the IVSRO group. Conversely, no significant
differences were seen in the SSRO group throughout theobservation period. Significant differences were identified
between the groups at T0–T1. The significant increasein postoperative IGW apparent in the IVSRO may be
attributed to the lack of rigid fixation and maximal
detachment of the medial pterygoid muscle from theproximal segment.
Ramus inclination increased significantly from T0
to T1, then decreased significantly from T1 to T2 in
the IVSRO group, but increased significantly from T0
to T1 in the SSRO group. Pan et al. reported that thechanges in ramus inclination angle had no influenceon stability of the distal segment in IVRO and thatclockwise rotation of the proximal segment during the
fixation procedure resulted in forward relapse of the
distal segment during remodeling after SSRO (11).
Although we do not believe that the stability of the
distal bony segment was affected by the lack of rigid
fixation in the IVSRO group, long-term follow-up isnecessary after both IVSRO and SSRO. Moreover, therelationship between the distal segment and ramus
inclination angle needs to be investigated in the future.
No significant difference in Me position was foundbetween the IVSRO and SSRO groups, remaining
within about 1 mm for both groups after surgery. This
result was clinically favorable for lateral stability of the
distal segment.
Limitations and Future Research
In this study, we were unable to standardize the surgeons.
In addition, the observation period was short, so verticalstability and segment changes were not able to be fully
evaluated. Future work should therefore conduct longterm follow-up of IVSRO and SSRO performed by thesame surgeon to address these limitations.
80

Hasumoto/Demura/et al.

Conclusions
IVSRO and SSRO both provide good stability whenused for the correction of mandibular protrusion andmandibular deviation. IVSRO leads to an increase in
IGW, which gradually decreases within approximately
10 months after the procedure.
Conflicts of Interest
The authors declare that they have no competing interests.
Funding
None
Ethics Approval
The study protocol was approved by the committee for
medical research ethics in Kanazawa Medical University(reference no. I307).
Acknowledgements
None

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9. Hashemi HM: Evaluation of intraoral verticosagittal ramus osteotomy forcorrection of mandibular prognathism: a 10-year study. J Oral Maxillofac Surg
2008; 66: 509-12.
10. Kitahara T, Nakasima A, Kurahara S et al: Hard and soft tissue stability oforthognathic surgery. Angle Orthod 2009; 79: 158-65.
11. Pan JH, Lee JJ, Lin HY et al: Transverse and sagittal angulations of proximal
segment after sagittal split and vertical ramus osteotomies and their influenceon the stability of distal segment. J Formos Med Assoc 2013; 112: 244-52.
12. Al-Moraissi EA, Ellis E 3rd: Is there a difference in stability or neurosensory
function between bilateral sagittal split ramus osteotomy and intraoral
vertical ramus osteotomy for mandibular setback? J Oral Maxillofac Surg
2015; 73: 1360-71.
13. Bayat M, Badri A, Momen-Heravi F et al: Transverse displacement andangulation of the proximal segment after mandibular setback by mean ofbilateral intraoral vertico-sagittal ramus osteotomy. J Oral Maxillofac Surg
2011; 69: 906-10.

J Kanazawa Med Univ 48：81 −84, 2023

Survey of the Review Process for Approved Animal Protocols and Feedback to
Education and Training
Shintaro Matsuba 1, 2), Ryoya Yamamoto 3), Yasuhito Ishigaki 1), Hirofumi Nishizono 1)*
1)

Research Support Center, Medical Research Institute, Kanazawa Medical University
Pharmacy Division, Kanazawa Medical University Hospital3)
Research Promotion Division, Kanazawa Medical University
2)

Abstract: Background: Laboratory animals are widely used in life sciences, research on the causes of
diseases and their remedies, and to confirm their safety. Many countries have adopted laws and guidelines
to ensure the ethical appropriateness of animal experiments. The Institutional Animal Care and Use
Committee (IACUC) has been established at each university and research institute to monitor and manage
the humane use of animal experiments. The Kanazawa Medical University (KMU) - IACUC plays acrucial role in monitoring and managing the humane use of animals in research across the university.
KMU-IACUC is responsible for both animal protocol review and education and is also required to update
the contents of its education and training to keep up with the latest research.
Methods: We investigated the reviewer’s comments on animal experiment protocols in the KMU review
process over the past three years and identified common issues in many applications by recounting thereview comments of animal protocols.
Results and Conclusion: There was a trend toward more reviewer comments in the following categories:
euthanasia, anesthesia, and pain control. Taken together, we have identified that new educational resources
need to be developed for euthanasia, anesthesia, and pain relief. Our approach can help improve theeducation and training related to animal experimentation.
Key Words: animal protocols, education and training, animal experiments, institutional animal care and use committee

Introduction
Laboratory animals are widely used in life sciences,
research on the causes of diseases and their remedies,and to confirm their safety. Although the use ofalternative methods is increasing owing to growing
public concern, it is not easy to completely replace
animal experiments, and the use of laboratory animals
will continue to be essential. Many countries haveadopted laws and guidelines to ensure ethicallyappropriate animal experiments. The Institutional Animal
Care and Use Committee (IACUC) has been establishedin each university and research institute to monitor andmanage the humane use of animal experiments (1-7).
1)Kohzaburo Fujikawa-Yamamoto
Division ofSupport
Cell Medicine,ResearchResearchInstitute Institute,of Medical
Science,* ResearchCenter, Medical
Kanazawa
Kanazawa
Medical 1-1
University,
920-0293,
Medical
University,
Daigaku,Uchinada,
Uchinada,Ishikawa
Kahoku, Ishikawa
Japan
920-0293,
Japan
Corresponding
author:Kohzaburo Fujikawa-Yamamoto
Email: hirofumi@kanazawa-med.ac.jp
Accepted:
Accepted:November
December30,
11,2006
2023

In Japan, the need for appropriate animal care andmanagement and experimental methods in animal
experiments is stated in the “Act on Welfare andManagement of Animals,” the “Standards relating to theCare and Keeping and Reducing the Pain of Laboratory
Animals,” and the “Fundamental Guidelines for Proper
Conduct of Animal Experiment and Related Activitiesin Academic Research Institutions” (8-10). In particular,
the fundamental guidelines clearly state that when
conducting animal experiments using experimental
animals for education or research, the animal protocols
must be prepared by principal investigators (PIs) andreviewed and approved by the IACUC. Animal
experiments conducted at Kanazawa Medical University(KMU) are also required to comply with the law andguidelines and the PIs must submit animal protocols
and must be approved by the IACUC of KMU (KMUIACUC) before conducting the animal experiments (11).
KMU-IACUC plays a crucial role in monitoring andmanaging the humane use of animals in research across81		

the university. It was established in 1993 and advocates
implementing the 3Rs that take initials of replacement,
reduction, and refinement concerning animal research(12, 13), when PIs propose experiments. KMU-IACUC
is organized by the president and consists of an animal
facility director, qualified individuals with experiencein animal experiments, talented individuals withexpertise in laboratory animals and animal ethics, andother qualified individuals with academic knowledge.
The KMU-IACUC reviews more than 100 animal
protocols annually. In addition, it is stipulated that KMUIACUC provides education and training for animal
experiments and that PIs and other animal experimentersmust obtain the latest knowledge and experience toconduct animal experiments (11). Thus, KMU-IACUC
is responsible for both animal protocol review andeducation and is also required to update the contentsof its education and training to keep up with the latest
research and other developments.
This report summarizes the activities of the KMUIACUC over the past three years. As a result of
scrutinizing the reviewer comments of the members in
the review process of animal protocols, it became clearthat there were some tendencies.
Materials and Methods
The data were used as animal protocols submitted toKanazawa Medical University and reviewed by the
IACUC from 2019 to 2021. All experiments in theexperimental protocol used in this study were basedon institutional rules and regulations of the Guide for
the Care and Use of Laboratory Animals (https://grants.
nih.gov/grants/olaw/guide-for-the-care-and-use-oflaboratory-animals.pdf). This study was conductedfollowing the Code of Ethics for Life Science andMedical Research Involving Human Subjects at
Kanazawa Medical University.
Counting of review comments.
The number of reviewer comments was collected fromthe review process of approved animal protocols overthe past three years and categorized by issue or keyword.
The issues, including experiment protocol, reductionof pain, methods of euthanasia, species and number ofanimals used, distress assessment, humane endpoints,
animal feeding, storage facility, mating, experimenter,animal laboratory, the purpose of animal experiments,
classification of experiments, disposal of animal
carcasses, and others, were selected from the animal
protocol format in Kanazawa Medical University (11).
For example, the comments regarding anesthesia andanalgesics were included in the category of “reductionof pain.” The percentages were calculated as follows: thenumber of reviewer comments on the indicated issue or
keywords/numbers of the total reviewer comments.
82

Matsuba/Yamamoto/et al.

Statistics.
All statistical analyses were performed using GraphPad
Prism software version 8.4.3 (GraphPad, San Diego,
CA, USA).

Results
The Institutional Animal Care and Use Committee
identified several issues with each animal protocol
at Kanazawa Medical University.
We collected data on the review process of animal
protocols conducted by the IACUC to improve thetraining of researchers in animal experimentation. The
average number of animal protocol applications andreviews at Kanazawa Medical University was 120.3 ±8.7 per year. During the study period, 13 protocols
were withdrawn: 6 in 2019, four in 2020, and three in
2021. The reasons for the withdrawals included theclosure of laboratories due to COVID-19 and changes
to other animal protocols during the proposal review
process. Twelve to fourteen members of the IACUC
reviewed these animal protocols. The committee’s
composition during this period was as follows: one
director of an animal facility, 6-8 qualified individuals
with experience in animal experiments, three experts
in laboratory animals and animal ethics, and two otherknowledgeable individuals. Experts in laboratory
animals were individuals who had experience in animal
experiments and specialized in veterinary medicine orlaboratory animal ethics. The review process is
illustrated in Figure 1. First, the protocol of the PI is

Figure 1. Review process of the animal protocol.
The animal protocols are reviewed by the Institutional Animal Care and
Use Committee (IACUC). First, the protocols are pre-checked by several
members of the IACUC, and if necessary, revisions are requested. Second,
the resubmitted protocols are reviewed by all members of the IACUC,
and only protocols that meet the criteria are approved.

Animal Protocol Review Process and Feedback

reviewed by several members of the IACUC. This
process is called the pre-check process. The IACUC will
request a revision by the PI if problems are found during
the pre-check. Then, all IACUC members review theanimal protocol which passes the pre-check (called themain review). An average of 7.9 ± 5.1 revisions werenoted by the IACUC per animal protocol (Fig. 2). The
average number was not significantly different from year
to year (F = 2.662, P = 0.0745, one-way ANOVA). In
addition, the required for the review were 30.3 ± 38.5

Figure 2. Total number of reviewer comments per protocol in 2019-2021.
The number of reviewer comments per approved animal protocol wascounted during the review process and plotted over the past three years.
Circles indicate the number of comments per protocol. Horizontal bars
represented the mean. The number of comments was the total number ofpre-checks and main reviews. Total number of protocols was 14 in 2019,
66 in 2020, and 28 in 2021.

days in 2019, 34.3 ± 14.7 days in 2020, 65.6 ± 35.8 daysin 2021. Furthermore, the number of experimental
animals used annually was 11940 ± 843 during the past
three years at Kanazawa Medical University (Table 1);
the average number was not significantly different fromyear to year. To identify which parts of the training
content were deficient before the animal experiments, weanalyzed the major revisions pointed out by the IACUC.
Although the numbers varied over the three years, themost frequent comments were about experimental
methods and reducing animal pain (Fig. 3). Although
the percentages ranged somewhat over the three years,
the comments on experimental protocols, methods of
reducing pain, and euthanasia methods accounted for
50% of the total comments in all years. Interestingly,
while the number of animals used decreased yearly(Table 1), the percentage of comments on the numberof animals used in the planning phase increased. The
number of comments on humane endpoints also
increased from year to year.

Discussion
We investigated the animal protocols at Kanazawa
Medical University for the past three years and identified
common issues in many applications by recounting thereview process of animal protocols. In the Figure 3, thereviewer’s comments were more frequent for euthanasia,
anesthesia, and pain control, indicating that the PI’s
knowledge of these issues is not at the level requiredby the IACUC, or that the explanation in the protocol

Table 1. Species of used experimental animals in 2019-2021.

Year
Species

2019

2020

2021

Mouse

10,531

10,637

9,749

Rat

1,682

1,443

908

29

15

0

Hamster
Mongolian gerbil

11

37

48

Rabbit

200

224

218

Gunia pig

29

11

46

Dog

3

0

0

Total

12,485

12,367

11,940The number of experimental animals used, sorted by
species, during the past three years, has been shown.

Figure 3. Stacked bar chart by category of reviewer comments in 2019-2021.
Reviewer comments in the review process were sorted by category, andthe percentages are shown for the indicated year. Categories were selectedbased on issues in the animal protocol.

83

		

is insufficient. These categories of comments relate to
the refinement of 3R principles (12, 13). Pre-animal
experiment education at Kanazawa Medical University
is standardized by the Japanese Association of Laboratory
Animal Facilities of National Corporations and theJapanese Association of Laboratory Animal Facilities of
Public and Private Universities. However, our results
suggest that these standard educational programs require
further updates to refine individual animal experiments.
These issues can be used as areas for improvement ofeducational processes. As in other countries where
animal experimentation is reviewed based on the 3Rs
principle (4-7), Japanese law also requires that animal
experimentation be reviewed based on this principle9.
The committee of Kanazawa Medical University madethe IACUC review mandatory as soon as the law on
animal experiments started in Japan. On the other
hand, the laws related to animal testing are revised
approximately every five years. When the law ischanged, scientists, legislators, citizens, and others
provide their opinions, and the law is revised based onthese opinions. Three years have passed since ouruniversity changed its old review system following
the latest legal update. We conducted this survey tounderstand the current problems and found scope forsome improvements that could be made in the educationand training of PIs who prepare animal experimental
plans. These improvements are mainly related toeducation on refinement, which we believe can besolved by providing the IACUC with information onanesthesia and euthanasia methods, the latest researchon experimental methods, etc.
Our study was limited to scrutinizing the animal
protocol review process at Kanazawa Medical University
during the past three years. We must carefully consider
whether these trends are similar in other universities.
However, verification of applications can be conductedby different institutes and universities. Thus, thesefindings could help improve the education and training
related to animal experimentation.

84

Matsuba/Yamamoto/et al.

Acknowledgements
The authors would like to thank the IACUC membersof Kanazawa Medical University for supporting thisresearch.
Conflict of Interest
All authors declare no COI for disclosure.
References

1. The National Research Council: The eighth edition of the guide for thecare and use of laboratory animals. https://olaw.nih.gov/sites/default/
files/Guide-for-the-Care-and-Use-of-Laboratory-Animals.pdf. (accessed on
October 14, 2022)
2. FELASA (Federation of European Laboratory Animal Science Associations):
FELASA recommendations on the education and training of persons working
with laboratory animals: Categories A and C. Reports of the Federation ofEuropean Laborator y Animal Science Associations Working Group on
Education accepted by the FELASA Board of Management. Lab Anim 1995;
29: 121-31.
3. Vardigans C, Malloy M, Meynell L: Breaking barriers to ethical research:
An analysis of the effectiveness of nonhuman animal research approval in
Canada. Account Res 2019; 26: 473-97.
4. Mohan S, Foley PL: Everything you need to know about satisfying IACUC
protocol requirements. ILAR J 2019; 60: 50-7.
5. Ahn N, Roh S, Park J: The status and issues of the Institutional Animal Careand Use Committee of Seoul National University: from its establishment to
the present day. Exp Anim 2021; 70: 532-40.
6. Diaz L, Zambrano E, Flores ME et al: Ethical consideration in animal
research: The principle of 3R s. Rev Invest Clin 2021; 73: 199-209.
7. Zutphen BV: Invited international perspective: education and training forthe care and use of laboratory animals: an overview of current practices.
ILAR J 2007; 48: 72-4.
8. Act on Welfare and Management of Animals (Act No. 105 of October 1,
1973). https://www.env.go.jp/nature/dobutsu/aigo/1_law/files/aigo_
kanri_1973_105_en.pdf. (accessed on October 14, 2022)
9. Standards relating to the Care and Keeping and Reducing Pain ofLaboratory Animals (Notice of the Ministry of the Environment No. 88 of
2006). https://www.env.go.jp/nature/dobutsu/aigo/2_data/laws/nt_
h25_84_en.pdf. (accessed on October 14, 2022)
10. Fundamental Guidelines for Proper Conduct of Animal Experiment andRelated Activities in Academic Research Institutions (Notice of the
Ministry of Education, Culture, Sports, Science and Technology No. 71 of2006). https://www.lifescience.mext.go.jp/policies/pdf/an_material011.
pdf. (accessed on October 14, 2022)
11. The regulations on Animal Experimentation at Kanazawa Medical
University, https://www.kanazawa-med.ac.jp/souiken/assets/KMU_
doubutsujikken_kitei.pdf. (in Japanese, translated by the author of thisarticle, accessed on October 14, 2022)
12. Russell WMS, Burch RL: The Principles of Humane Experimental
Technique, London, Methuen, 1959.
13. Smyth D: Alternatives to Animal Experiments, London, Scolar Press, 1978.

J Kanazawa Med Univ 48：85 −86, 2023

Clinical Images: Megakaryocytic Emperipolesis in a Patientwith Myelodysplastic Syndrome
Naoki Okada, Reiko Fujisawa, Yutaka Saikawa, Hitoshi Sato*
Department of Pediatrics, Kanazawa Medical University

Key Words: megakaryocytes, emperipolesis, myelodysplastic/myeloproliferative neoplasm

A previously healthy 11-year-old girl presented with
fatigue and dizziness during light exercise. Physicalfindings were unremarkable except for conjunctival
pallor. Blood count showed hemoglobin 8.6 g/dL,
white blood cells 6,100/μL with 6.0% blast cells, andplatelets 1,050x103/μL. Bone marrow examination withchromosomal analyses showed 80% hemopoietic
cellularity with a 45,XX,-7 karyotype, erythroid
hypoplasia in the absence of ring sideroblasts, dysplastic
granulocytes with 15% CD34-positive blasts, andnumerous dysplastic megakaryocytes with emperipolesisof hematopoietic cells (Figure 1, aspirate smear, MayGrünwald-Giemsa stain; Figure 2, biopsy specimen,
hematoxylin and eosin stain). Additional cytogenetic
analyses fulfilled a diagnosis of myelodysplastic/
myeloproliferative neoplasm, unclassifiable, associatedwith monosomy 7. The patient underwent allogeneic
stem-cell transplantation and remains in complete
remission 8 years after transplantation. Megakaryocytic
emperipolesis observed at diagnosis had disappeared
after transplantation.
Emperipolesis is a cell-in-cell phenomenon inwhich living cells penetrate into an another cell, andmegakaryocytic emperipolesis is most commonly seenin this condition (1). Emperipolesis differes fromphagocytosis in that an enclosed cell retains an intact
normal structure, while in phagocytosis, the engulfed
cell is destroyed by the digestive activity of lysosomes*1)Kohzaburo
DepartmentFujikawa-Yamamotoof Pediatrics, Kanazawa Medical University, 1-1
Division ofUchinada,
Cell Medicine,Research
Instituteof Medical
Daigaku,
Kahoku,Ishikawa
920-0293,
Japan Science,
Kanazawa
Medical University,
Uchinada, Ishikawa 920-0293,
Tel: +81-76-218-8133,
Fax: +81-76-286-8918
Japan
Email: p-hsato@kanazawa-med.ac.jp
Corresponding
author:Kohzaburo
Accepted: December
14, 2023 Fujikawa-Yamamoto
Accepted: November 30, 2006(1). This phenomenon can be seen in physiologic
conditions but is frequently observed in hematolymphoiddisorders such as autoimmune hemolytic anemia,
immune thrombocytopenic pupura, myeloproliferative
neoplasms, and myelodysplastic syndromes (2).
Although megakaryocytic emperipolesis is of uncertain
significance, an increased number of megakaryocytic
emperipolesis may represent part of abnormal
hematopoiesis in the present case with myelodyplastic
syndrome.

Figure l. Bone marrow aspirate: a dysplastic megakaryocyte withemperipolesis of a segmented neutrophil (May-Grünwald-Giemsa stain,
original magnification x1000). An arrow and an arrowhead indicate theneutrophil and the nucleus of the megakaryocyte, respectively.

85

		

Okada/Fujisawa/et al.

Authors’ disclosures of potential conflicts of interest
The authors declare that there are no potential conflictsof interest.
References

1 . Cunin P, Nigrovic PA: Megakaryocyte emperipolesis: a new frontier in cellin-cell interaction. Platelets 2020; 31: 700-6.
2 . Cashell AW, Buss DH: The frequency and significance of megakaryocytic
emperipolesis in myeloproliferative and reactive states. Ann Hematol 1992;
64: 273-6.

Figure 2. Bone marrow biopsy: numerous dysplastic megakaryocytes withemperipolesis of neutrophils or lymphocytes (hematoxylin and eosin stain).
A bar represents 50 μm.

86金医大誌（J Kanazawa Med Univ）48：87 − 89, 2023

金沢医科大学医学会記録
第49 回医学会総会
第58 回学 術 集 会2022 年度金沢医科大学学長賞受賞講演
嗅上皮傷害マウスにおけるマウス脂肪幹細胞経鼻投与による嗅上皮再生石倉友子 a，志賀英明 a，中村有香 b，蟹谷貴子 a，石垣靖人 b, c，

日時：2023 年 7 月15 日 ( 土 ) 13 : 30 〜

三輪高喜 a（a 耳鼻咽喉科学，b 総合医学研究所 生命科学研究

場所：金沢医科大学 医学教育棟4 階 E41 講義室

領域，c 再生医療センター）【目的】嗅上皮傷害モデルにおいて脂肪幹細胞静脈投与による嗅上皮再生効果の報告がある。一方で脂肪幹細胞静脈投与は血栓特別講演症が危惧される。本研究では，嗅上皮傷害モデルへのGFP トラ

精神性発汗の評価法とその異常

ンスジェニックマウスの脂肪幹細胞の経鼻投与が，嗅覚忌避行

朝比奈正人（脳神経内科学）
発汗は温熱性発汗と精神性発汗に大別される。前者は全身の有毛部にみられる発汗で，その生理学的意義は暑熱暴露時や運動時に身体を冷却することである。一方，後者は手掌や足底の無毛部にみられる発汗で，その生理学的意義は物をつかんだり
指先で繊細な作業をする際のすべり止めである。精神性発汗
は，精神的ストレスで誘発される以外に，深呼吸（息こらえ），運
動負荷，手掌 ・ 足底への触刺激などでも誘発される。精神性発汗の発現には，大脳辺縁系，脳幹網様体，交感神経節前神経，交感神経節後神経などが関与しており，その記録は精神活動の指標や自律神経障害の評価に用いられている。
手掌の発汗の評価法としては，古くから皮膚電気活動の記録が用いられている。心理学領域では，皮膚コンダクタンスが用いられることが多く，臨床神経領域では電気刺激に対する皮膚電位反応（交感神経性皮膚反応）を測定することが多い。しかし，皮膚電気活動は定性的指標であり，実際の発汗量を反映するものではない。精神性発汗の定量的評価には，カプセル換気法による発汗計が用いられる。その他の評価法としては，光コ
ヒーレンス法による汗管内の汗の3 次元画像解析やダーモスコ
ピーによる観察などがある。
精神性発汗の発現に関連する中枢 ・ 末梢神経に病変があると精神性発汗は障害される。長期経過の糖尿病では末梢神経障害が必発であり，末梢自律神経が障害されることで精神性発汗が障害される。脊髄では錐体路の前面に交感神経下行路が存在す動の回復と嗅上皮の再生を促進するのかを検討した。
【方法】8 週齢オスのC57BL/6J マウスにおいて，嗅上皮傷害作用を有するメチマゾールの腹腔内投与前後に，酪酸臭に対する忌避行動を評価した。メチマゾール腹腔投与の7 日後にマウスの左鼻孔に脂肪幹細胞または生理食塩水を経鼻投与した。成熟嗅細胞マーカーやその他の因子は，鼻腔の上皮における免疫組織
化学的染色によって評価した。また，脂肪幹細胞が分泌する神経栄養因子について，細胞調整液上清をELISA で解析した。
【結果】脂肪幹細胞経鼻投与14 日後に嗅覚忌避行動の回復は有意に増加しており，同時期の嗅上皮における成熟嗅細胞マーカー(OMP) の発現は，脂肪幹細胞投与群において，コントロール群よりも有意に増加した。嗅上皮のOMP 発現は経鼻投与7 日後から差が生じていた。GFP 陽性細胞は，脂肪幹細胞投与24 時間後に経鼻投与側の鼻腔に認めたが，3 日後には消失していた。ELISA
では脂肪幹細胞調整液上清に神経成長因子 (NGF) とBDNF の発現を認めた。また経鼻投与24 時間後の上皮ではKi-67，GFP 陽性
細胞周囲と鼻粘膜上皮内にNGF の発現を認め，コントロール群と比較して，脂肪幹細胞投与群で有意に増加していた。
【結論】脂肪幹細胞の経鼻投与は嗅上皮傷害モデルマウスにおける嗅覚再生を促進した。嗅細胞の発達，再生において神経栄養因子が必要であると考えられており，本研究から神経栄養因子を分泌する脂肪幹細胞が嗅細胞の再生促進に関与したと考察された。今後，培地の差で因子分泌などどのように差が出るのかを検討したい。

るとされ，この経路の障害で精神性発汗が障害される。延髄では延髄外側に交感神経下行路があり，この経路が障害されると精神性発汗が障害される可能性がある。情動の中枢でもある辺縁系は，精神性発汗の中枢でもある。特に扁桃体が障害されると精神性発汗は障害される。このように神経疾患における精神性発汗の測定は病変部位の推定や障害の程度を評価するのに役
立つ。

一般口演
1. 脂肪由来幹細胞を用いた変形性膝関節症の幹細胞療法における滑液の影響坂本卓弥 a，北島宏矩 b，福淳史 b，堀江哲寛 c，桑野彩音 d，

中村有香 ，谷田育宏 ，石垣靖人 a, c，市堰
cd

徹 b，大澤敏 d，

川原範夫（ 総合医学研究所 共同利用センター， 整形外科学，
b a

c

b

総合医学研究所 生命科学研究領域，d 金沢工業大学バイオ ・化学部・応用化学科）
変形性膝関節症（膝OA）は肥満，老化，外傷などの要因により，関節軟骨が徐々に変性することで慢性的な疼痛や運動障害を引き起こす不可逆的な疾患である。治療法としては，対症療法が原則であるが，改善が認められない場合は外科的治療として人工関節置換術が行われている。しかし，対症療法により疼痛コ87		
ントロールができない患者や手術適応を拒む患者もおり，治療【対象 ・ 方法】Wister 系雄性ラットを用い，神経原性炎症を血管選択肢が少ないのが現状である。一方で，最近は再生医療を応

透過性（エバンスブルー）サブスタンス P (ELISA) と炎症関連用した幹細胞療法が普及しつつある。特に採取が容易で低侵襲mRNA で評価した。末梢性疼痛シグナルと脊髄−腕傍核−扁桃である脂肪由来幹細胞 (ADSC) が，膝 OA の幹細胞療法に用いら体路の活性化について，炎症 ・ 酸化ストレス関連 mRNA，脊髄れている。ADSC の投与部位である関節腔は滑液で満たされて−腕傍核−扁桃体経路でのpERK やc-Fos 発現の免疫蛍光，さらいるが，治療用 ADSC に与える影響はほとんど明らかにされてに坐骨神経ブロックにて評価した。病的疼痛である触覚アロいない。本研究では膝 OA のADSC 細胞治療において投与されたディニアの発現の有無は，Aβニューロンにチャネルロドプシン

ADSC が膝 OA 患者由来滑液に暴露された時の影響を検討した。

2 を発現するW-TChR2V4 ラットを用いた光遺伝学的行動評価【方法・結果】
実臨床の治療プロトコールではADSC は生理食塩水

で，また冷痛覚過敏の発現の有無はアセトン試験で評価した。

に懸濁してから膝関節内に投与されるが，生理食塩水に懸濁した【結果 ・ 結論】ギプス固定された後肢において，血管透過性やサ

ADSC は，膝 OA 由来の滑液に暴露されることでADSC の生細胞

ブスタンス P，炎症性および酸化ストレス関連のmRNA が増加し率が有意に向上した。また，生細胞率向上のメカニズムを探索すた。また脊髄−腕傍核−扁桃体経路においてpERK およびc-Fos

るためにADSC の滑液暴露による網羅的遺伝子発現変動を解析しの免疫蛍光が増加した。また光遺伝学的に誘発される触覚アロたところ，多くの細胞増殖・生存に関与する遺伝子が変動していディニアや冷痛覚過敏が生じた。これらは，坐骨神経ブロックにた。その中で，我々は癌幹細胞において細胞生存や増殖に関与すより抑制された。以上により，身体不活動は，神経原性炎症およるFOSL1 に着目した。遺伝子発現解析の結果を裏付けるためにび脊髄-腕傍核- 扁桃体経路の活性化を介して，触覚アロディニア

滑液を暴露したADSC のFOSL1 の発現上昇をRT-PCR およびウエを代表する病的疼痛の発現に寄与することが示唆された。

スタンブロットにより確認したところ，同様の結果が得られた。
またADSC における滑液暴露による細胞生存率上昇にFOSL1 が寄与を証明するために，siRNA によりADSC のFOSL1 をノックダ

3. 口腔細胞診への人工知能の応用－細胞核検出と背景差分法について－ウンしたところ滑液による細胞生存率が有意に低下した。

見立英史 a，尾山（山口）武 b，武田啓太 c，酒井智弥 c，下本陽一 d，【結論】本研究からKnee OA の滑液はADSC におけるFOSL1 の発

山本郁夫 d，角美佐 e，山内陽太 a，出村太一 a，加藤崇雄 a，

現を上昇させ，関節腔内における細胞生存に寄与していた。自中野旬之 a，出村

昇 a（a 顎口腔外科学，b 臨床病理学，c 長崎

家培養 ADSC による変形膝関節症の治療においてFOSL1 を標的

大学情報データ科学部，d 長崎大学大学院工学研究科，e 長崎とすることは，関節腔内での細胞生存率の向上を目的とした細大学大学院口腔診断・情報科学分野）

胞製剤の開発に繋がることが期待される。

【緒言】希少がんである口腔がんに対し，擦過細胞診は簡便な検【謝辞】本研究は金沢工業大学との医工連携協定に基づき実施さ査法であり，早期発見に有用である。子宮頸部細胞診では人工れたものである。また本研究は科研費 (22K16779) の支援を受

知能 (AI) が導入されていることから，口腔細胞診においても診けた。

断の省力化のためAI 導入が有用と考えた。その導入にあたり(1) 細胞診画像中の青染細胞から細胞核を自動検出する方法 (2)2. 身体不活動は，神経原性炎症と脊髄 - 外側腕傍核 - 扁桃体経

背景差分法について検討した。

路の活性化を通じて，広範囲機械痛覚過敏，触覚アロディ【方法】長崎大学病院口腔外科で施行された口腔細胞診症例を対ニア，冷痛覚過敏に寄与する物40 倍で撮影し，tiff 形式で保存した。

大道裕介 ，大道美香 ，田島諒一 ，大須賀浩二 ，Dominika(1) 各画像を96×96 pixel に分割し，591 枚を訓練群，197 枚をテ

Kanikowska d，深澤有吾 e，八尾

誠 b（a 解剖学Ⅱ，

スト群としてSliding Window 法（SWM）を適用した。またClass

九州大学大学院薬学研究院薬理学分野，c 愛知医科大学医学

II およびIII 症例の画像を各130 枚用意し，細胞領域を示すマス

部脳神経外科学講座， Poznań University of Medical Sciences,

ク画像を作成し，Mask-RCNN に入力した。

Poland，e福井大学医学部脳形態機能学，f東京大学物性研究所）(2) 訓練群20 例，評価群6 例，テスト群5 例（計5041 枚）Dual-

a

b

a

b

寛 f，津田cd【目的】運動による痛みへの恐怖 (kinesiophobia) や不適切な安静

frame U-Net に入力した。

処置などによる身体不活動は，痛みの悪循環を形成し，複合性局【結果】(1) SWM 法で評価群における青色染色細胞の検出率は

所疼痛症候群 I 型を代表とする難治性疼痛の発症につながる可能

0.9314 であった。Mask-RCNN では37 個の細胞核が識別され，性がある。しかし身体不活動が急性 / 慢性痛やその他の病理学的40 epoch 後に1 個の細胞核が非核と識別された（エラー率 ：徴候と関連する機序は未解決のままである。本研究では，独自に0.027）。(2) 正診率は背景除去前が81±2％，背景除去後が76±開発したギプス固定後慢性疼痛 (CPCP) モデルラットを用い，身3％となった。

体不活動により末梢性疼痛シグナルや神経原性炎症が発現する【考察】細胞核を識別することで，診断すべき細胞をAI が認識でかを調査した。またこれらが疼痛関連経路である脊髄−腕傍核きる可能性が示唆された。また細胞診においても背景バイアス−扁桃体路を活性化させるか，本経路の活性化が触覚アロディニ問題が存在する可能性が示唆された。

アを代表とする病的疼痛の発現に寄与するかを調査した。
88

4. 核白内障における環境温度の変化に伴う水晶体中ミトコン
ドリア機能について
武田

培養したヒト上皮細胞株 SRA01/04 とiHLEC-NY2 の2 種を用い

峻 ，山本直樹 ，初坂奈津子 ，平松範子 ，長井紀章 ，ab

出口粧央里 c，中澤洋介 d，高田

【方法】実験には低温（35.0℃）または高温（37.5℃）環境下で4 日間

a

b

c

た。またリアルタイム PCR を用いてシトクロム c オキシダーゼ

匠 e，小寺紗千子 f，平田晃正 f，(CCO) 遺伝子発現量の変化を確認し，CCO アッセイキットを用

久保江理 a，佐々木洋 a（a 眼科学，b 藤田医科大学，c 近畿大学，いることでCCO活性を評価した。ATPはルシフェリン-ルシフェ

慶應義塾大学， 京都大学複合原子力科学研究所， 名古屋工

ラーゼアッセイ法により測定した。

業大学）【結果】両細胞株において高温条件下（37.5℃）での培養により細

d

e

f

【背景】白内障病型のひとつである核白内障は，これまでの疫学

胞増殖が有意に促進され，SRA01/04 およびiHLEC-NY2 いずれ

調査にて有病率は人種に関係なく，熱帯または亜熱帯地域で著においても，ミトコンドリアゲノムであるCCO (CCO-1, 2, 3) 遺

しく高いことを見出した。また計算機シミュレーションにより伝子発現量とその活性は低温培養群に比べ高温培養群で高値を環境温度の上昇に伴い水晶体温度も上昇し，累積熱負荷と核白示した。またATP 量も両細胞株ともに高温培養群では低温培養

内障発症率との間には相関性があることを報告した。このよう群に比べ有意に高かった。

に高温環境での長期間ばく露は核白内障発症リスクを高める【結論】高温培養下でミトコンドリアゲノムのCCOの発現と活性が，その詳細な機序については十分には明らかとされていなが高まり，十分なATP 量と細胞増殖が得られることが確認されい。本研究ではヒト水晶体上皮細胞を用いて，水晶体機能維持た。また，これらミトコンドリア活性化によるATP 産生増加が，に関わるミトコンドリア機能や細胞増殖能が低温または高温環

水晶体上皮細胞の増殖を介した細胞密度の増加に寄与している

境下でどのように変化するかについて検討した。

可能性を示した。これらの結果は，核白内障の有病率と環境温度の上昇との関係を読み解く上で重要な知見であると考える。

89

金沢医科大学医学会
2023 年度（第29 回）「論文表彰」募集要項
１．趣旨
本表彰制度は、医学会の 20 周年を記念して本学医学会の若手研究者の育成と医学研究の充実発展に寄与することを目的とし、制定したものである。
2

対象論文(1) 本学医学会会員の過去 1 年間（2022 年 1 月〜 2022 年 12 月）に公表された論文（英文）を対象とし、単著論文、共著論文いずれも可とする。
※1(2) 論文の公表誌は、英文でインパクトファクター（JCR 最新版 2021 年）を有する雑誌とする。

(3) 論文は、｢ 原著 ｣、｢ 総説 ｣、｢ 症例報告 ｣ 及びそれらと同等の内容のものとする。
(4) 論文の筆頭所属機関が本学の場合に限る。
３．申請資格(1) 申請者は、50 歳未満（2023 年 4 月 1 日現在）の本学医学会会員とする（教授を除く）。
(2) 申請者は、筆頭著者のみとする。
(3) 申請は、1 人 1 編とする。
４．申請方法所定の申請書に必要事項を記入押印のうえ、別刷 1 部（コピー可）を添えて、2023 年 5 月 15 日（月）までに研究推進課へ提出するとともに、申請書 Word ファイルを電子メールで送信すること。
（Eメール：hrc-jimu@kanazawa-med.ac.jp）
５．選考方法
選考方法は、金沢医科大学雑誌編集委員会において審査を行い、医学会会長が決定する。
６．表彰
受賞者には、金沢医科大学医学会総会において表彰状並びに副賞を授与する※2。副賞は、1 件 5 万円とする。ただし、受賞者多数の場合は副賞の金額減額等による調整を行うものとする。
以上※ 1. Journal Citation Reports (JCR) のインパクトファクターのみ対象となります。いま一度ご確認ください。
URL：https://jcr.clarivate.com/※2.

90

受賞者は金沢医科大学医学会総会に出席してください。

金沢医科大学医学会
2023 年度（第29 回）「論文表彰」受賞者一覧※ 職名は受賞時のもの
1． 大井

一高

非常勤講師（総合内科学）

Shared genetic basis between reproductive behaviors and anxiety-related disorders. Molecular Psychiatry. 27: 4103-4112, 2022.

2． 福

淳史

助教（整形外科学）

Evaluation of the Usefulness of Human Adipose-Derived Stem Cell Spheroids Formed Using SphereRing® and the Lethal
Damage Sensitivity to Synovial Fluid In Vitro. Cells. 11: 337, 2022.

3． 髙田

尊信

講師（生命科学研究領域）

4． 野村

匡晃

助教（肝胆膵内科学）

5． 小屋

照継

助教（再生医療学）

6． 坂本

卓弥

助教（共同利用センター）

Intracellular Toxic Advanced Glycation End-Products in 1.4E7 Cell Line Induce Death with Reduction of MicrotubuleAssociated Protein 1 Light Chain 3 and p62. Nutrients. 14: 332, 2022.

Surgical implantation of human adipose derived stem cells attenuates experimentally induced hepatic fibrosis in rats.
Molecular Medicine. 28: 143, 2022.

The Detection of Immunity against WT1 and SMAD4P130L of EpCAM+ Cancer Cells in Malignant Pleural Effusion. International
Journal of Molecular Sciences. 23: 12177, 2022.

Different In Vitro-Generated MUTZ-3-Derived Dendritic Cell Types Secrete Dexosomes with Distinct Phenotypes and Antigen
Presentation Potencies. International Journal of Molecular Sciences. 23: 8362, 2022.

7． 硎

澄仁

講師（先端医療研究領域）

Genotype and Phenotype Landscape of 283 Japanese Patients with Tuberous Sclerosis Complex. International Journal of
Molecular Sciences. 23: 11175, 2022.

8． 津元

国親

准教授（生理学Ⅱ）

9． 初坂

奈津子

Bifurcations and proarrhythmic behaviors in cardiac electrical excitations. Biomolecules. 12: 459, 2022.

助教（眼科学）

Vision With Retrodots and Factors for Declining Visual Function. Investigative Ophthalmology & Visual Science. 63: 17, 2022.

10．浦

大樹

講師（先端医療研究領域）

A comparison of mRNA sequencing (RNA-Seq) library preparation methods for transcriptome analysis. BMC Genomics. 23:
303, 2022.

11．酒井

大輔

講師（一般教育機構 生物学）

12．植田

修右

講師（整形外科学）

13．本野

望

14．坂本

人一

Hif1α-dependent hypoxia signaling contributes to the survival of deep-layer neurons and cortex formation in a mouse model.
Molecular Brain. 15: 28, 2022.

Inhibitory effect of taurine on rotator cuff degeneration via mitochondrial protection. American Journal of Translational
Research. 14: 6286-6294, 2022.

講師（呼吸器外科学）

PD-L1 Expression is not a Predictive Factor for Recurrence in Resected Non-small Cell Lung Cancer. Lung. 201: 95-101, 2023
(Published online 2022 Dec 30).

学内講師（産科婦人科学）

Determination of human papillomavirus type in archival tissue specimens of invasive cervical cancer using molecular mappingand E6/E7-based polymerase chain reaction. PLOS ONE. 17: e0265996, 2022.
91

15．飯島慶仁

講師（呼吸器外科学）

Is Overweight Related to the Prognosis of Octogenarians with Lung Cancer? Obesity Surgery. 32: 1279-1288, 2022.

16．二ツ谷剛俊

助教（皮膚科学）

Genotyping of Trichophyton tonsurans strains isolated between 2016 and 2020, and terbinafine susceptibility of the species inJapan. The Journal of Dermatology. 49: 691-696, 2022.

17．葛西

傑

18．安井

良僚

19．高原

豊

助教（腫瘍内科学）

Dual blockade of MET and VEGFR2 signaling pathways as a potential therapeutic maneuver for peritoneal carcinomatosis inscirrhous gastric cancer. Biochemical and Biophysical Research Communications. 600: 80-86, 2022.

講師（小児外科学）

Transplanted neural crest cells migrate toward Auerbach's plexus layer instead of the colon surface in recipient colon
pretreated with collagenase and fibronectin. Biochemical and Biophysical Research Communications. 601: 116-122, 2022.

准教授（呼吸器内科学）

Efficacy and predictors of rechallenge with immune checkpoint inhibitors in non-small cell lung cancer. Thoracic cancer. 13:
624-630, 2022.

20．硎

美紗

助手（再生医療学）

Herbal extracts that induce type I interferons through Toll-like receptor 4 signaling. Food & Nutrition Research. 66: doi:
10.29219/fnr.v66.5524, 2022.

21．牛本

知孝

講師（救急医学）

22．塩谷

晃広

講師（臨床病理学）

23．生駒

透

医員（眼科学）24．水戸

毅

准教授（眼科学）25．桑原

強学内講師（小児外科学）

26．安田

有志

助教（循環器内科学）

27．宮永

葵子

講師（看護学部）

28．柴田

健雄

講師（産科婦人科学）

29．東川

俊寛

准教授（高齢医学）

Effect of large-scale disasters on bystander-initiated cardiopulmonary resuscitation in family-witnessed, friend-witnessed andcolleague-witnessed out-of-hospital cardiac arrest: a retrospective analysis of prospectively collected, nationwide, populationbased data. BMJ Open. 12: e055640, 2022.

Recurrence of gastric adenocarcinoma of fundic-gland mucosa type with black spots after endoscopic submucosal dissection
and oral proton pump inhibitor discontinuation. Pathology International. 72: 430-432, 2022.

Acute cataract by a high-intensity focused ultrasound procedure: a case report. BMC Ophthalmology. 22: 164, 2022.

Positive dysphotopsia after intrascleral intraocular lens fixation: a case report. BMC Ophthalmology. 22: 263, 2022.

Recipient colon preoperative treatment with type I collagenase and fibronectin promotes the growth of transplanted entericneural crest cells into Auerbach's plexus. Pediatric Surgery International. 38: 1793-1798, 2022.

Glyceraldehyde-derived advanced glycation end-products are associated with left ventricular ejection fraction and brain
natriuretic peptide in patients with diabetic adverse cardiac remodeling. Scandinavian Cardiovascular Journal. 56: 208-216,
2022.

Patient experience of negative pressure wound therapy: A qualitative study. Nursing Open. 10: 1415-1425, 2023 (Published
online 2022 Oct 5).

A retrospective study of immunotherapy using the cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guérin (BCGCWS) for cervical cancer. Medicine. 101: e32481, 2022.

Orthogeriatric co-management at a regional core hospital as a new multidisciplinar y approach in Japanese hip fracture
operation. Journal of Orthopaedic Science. doi: 10.1016/j.jos.2022.11.002 (Published online 2022 Nov 26).

92

30．高村敬明

学内講師（循環器内科学）

31．小野

太輔

臨床准教授（高齢医学）

32．藤本

圭司

臨床准教授（腎臓内科学）

33．岩井

俊

助教（呼吸器外科学）

34．松葉

聖

助教（麻酔科学）

35．藤林

幸輔

Response to pre-dilatation with POBA can predict target lesion revascularization after DCB angioplasty for de novo small
coronary artery lesions. Journal of International Medical Research. 50: 3000605221113779, 2022.

Pharmacologic Management of Excessive Daytime Sleepiness. Sleep Medicine Clinics. 17: 485-503, 2022.

Early, Noninvasive Clinical Indicators of Kidney Prognosis in Primary Nephrotic Syndrome: A Retrospective Exploratory
Study. International Journal of Nephrology. 2022: 2718810, 2022.

Racemose hemangioma revealed by massive intraoperative hemorrhage: A case report. International Journal of Surgery Case
Reports. 91: 106722, 2022.

Anesthetic management in a patient with severe tracheal stenosis by monitoring oxygen reserve index. JA Clinical Reports. 8:73, 2022.

学内講師（循環器内科学）

A Case of Myopericarditis After the Second Dose of mRNA COVID-19 Vaccine in a Patient With a History of Myopericarditis.
Clinical Medicine Insights: Case Reports. 15: 11795476221138648, 2022.

93ISSN 2436-6994

金 沢 医 科 大 学 雑 誌

Vol． 48，2023

金沢医科大学医学会

編

集

金沢医科大学医学会

編集委員

西野 善一（委員長），清川 悦子（副委員長），朝比奈正人，岩脇 隆夫，
櫻井勝，高村 博之，林康彦，古市 賢吾，正木 康史，
山田 壮亮，米倉 秀人

金沢医科大学雑誌総目次
第 48 巻 第 1 〜 2 号

2023 年

総説
Toxic AGEs (TAGE) と健康：I. 細胞障害因子としての TAGE …………………………………………… 1
坂井 ( 逆井 ) 亜紀子，竹田 健史，竹内 正義
Toxic AGEs (TAGE) と健康：II. 生活習慣病予測マーカーとしての TAGE ……………………………… 12
竹内 正義，竹田 健史，坂井 ( 逆井 ) 亜紀子
Biodegradable Semi-Rigid Mitral Valve Annuloplasty Ring Designed for Children ……………………… 65
Makoto Ando, Takako Nishino

原著
Usefulness of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
in Prognosis of Primary Uterine Carcinosarcoma ………………………………………………………… 22
Hiroaki Takagi, Kazuki Mibe, Sakurako Takata,
Tsukasa Yamanouchi, Yoshihiko Saeki, Sumire Shimada,Emi Takata, Jinichi Sakamoto, Takeo Shibata, Satoko Fujita,
Masahiro Takakura, Naoto Watanabe, Toshiyuki Sasagawa
金沢医科大学病院での周術期 ( 等 ) 口腔機能管理の現状 ………………………………………………… 29
東川 久代，中野 旬之，村山 智子，山村真由美，新谷 麻美，
沖田奈々葉，水野 絢菜，首田 千尋，岡田真里奈，出村 太一，
山内 陽太，出村昇
Association of Dispatcher-Assisted Compression-Only Resuscitation with Survival Ratein Unwitnessed Out-of-Hospital Cardiac Arrest: A Temporal Trend
and Analyses of 8-Years Trend ……………………………………………………………………………… 33
Tomoyuki Ushimoto, Hideki Morita, Yukihiro Wato, Hideo Inaba
Decorin Improves Wound Contracture for the Treatment of Skin Defects in a Mouse Model …………… 43
Haotian Chen, Yasuo Yoshitomi, Kenichi Shimada,
Hideto Yonekura, Toru Miyanaga
Characteristic Clinical Features of Orthognathic Surgery Patients Encountered
Over 18year Period–a Retrospective Study ……………………………………………………………… 70
Miho Hasumoto, Taichi Demura, Hiroyuki Nakano, Yota Yamauchi,
Takao Kato, Eiji Mitate, Satoshi Wada, Noboru Demura
Stability Following Intraoral Vertico-Sagittal Ramus Osteotomy and Sagittal Split Ramus Osteotomy
for Asymmetric Mandibular Prognathism ………………………………………………………………… 76
Miho Hasumoto, Taichi Demura, Satoshi Wada, Yota Yamauchi,
Takao Kato, Eiji Mitate, Hiroyuki Nakano, Noboru Demura
Survey of the Review Process for Approved Animal Protocols and Feedback
to Education and Training ………………………………………………………………………………… 81
Shintaro Matsuba, Ryoya Yamamoto, Yasuhito Ishigaki,
Hirofumi Nishizono

症

例 報 告
An Adult Man with Incomplete Amputation of Traumatic Left Upper Arm withan Aggravated Clinical Course and Unexpected Asthma Attack: An Autopsy Case …………………… 54
Shuice Liu, Horyu Hirakawa, Jia Han, Motona Kumagai,
Akihiro Shioya, Sohsuke Yamada
Clinical Images: Megakaryocytic Emperipolesis in a Patient with Myelodysplastic Syndrome ………… 85
Naoki Okada, Reiko Fujisawa, Yutaka Saikawa, Hitoshi Sato		

CONTENTS OF VOLUME 48, 2023
Reviews
Toxic AGEs (TAGE) and Health: I. TAGE as a Cytotoxic Factor …………… 1

			

Akiko Sakai-Sakasai, Kenji Takeda, Masayoshi Takeuchi			

Masayoshi Takeuchi, Kenji Takeda, Akiko Sakai-Sakasai			Makoto Ando, Takako Nishino

Toxic AGEs (TAGE) and Health: II. TAGE as a Marker
of Lifestyle-Related Diseases ……………………………………………12
Biodegradable Semi-Rigid Mitral Valve Annuloplasty Ring Designed
for Children………………………………………………………………65

Original Articles
Usefulness of Fluorodeoxyglucose Positron Emission
Tomography/Computed Tomography in Prognosis
of Primary Uterine Carcinosarcoma ……………………………………22
			
Hiroaki Takagi, Kazuki Mibe, Sakurako Takata, Tsukasa Yamanouchi,			Yoshihiko Saeki, Sumire Shimada, Emi Takata, Jinichi Sakamoto,			Takeo Shibata, Satoko Fujita, Masahiro Takakura, Naoto Watanabe,			Toshiyuki Sasagawa

Current Status of Perioperative Oral Function Managementin Kanazawa Medical University Hospital ………………………………29

			
Hisayo Higashikawa, Hiroyuki Nakano, Tomoko Murayama,			Mayumi Yamamura, Asami Shintani, Nanaha Okida, Ayana Mizuno,			Chihiro Kubita, Marina Okata, Taichi Demura, Yota Yamauchi,
			Noboru Demura

Association of Dispatcher-Assisted Compression-Only Resuscitation
with Survival Rate in Unwitnessed Out-of-Hospital Cardiac Arrest:
A Temporal Trend and Analyses of 8-Years Trend ………………………33

			

Tomoyuki Ushimoto, Hideki Morita, Yukihiro Wato, Hideo Inaba

Decorin Improves Wound Contracture for the Treatment
of Skin Defects in a Mouse Model ………………………………………43

			
Haotian Chen, Yasuo Yoshitomi, Kenichi Shimada, Hideto Yonekura,			Toru Miyanaga

Characteristic Clinical Features of Orthognathic Surgery Patients
Encountered Over 18year Period–a Retrospective Study ………………70

			
			

Miho Hasumoto, Taichi Demura, Hiroyuki Nakano, Yota Yamauchi,
Takao Kato, Eiji Mitate, Satoshi Wada, Noboru Demura

Stability Following Intraoral Vertico-Sagittal Ramus Osteotomy
and Sagittal Split Ramus Osteotomy
for Asymmetric Mandibular Prognathism ………………………………76

			
			

Miho Hasumoto, Taichi Demura, Satoshi Wada, Yota Yamauchi,
Takao Kato, Eiji Mitate, Hiroyuki Nakano, Noboru Demura

Survey of the Review Process for Approved Animal Protocols
and Feedback to Education and Training ………………………………81

			
Shintaro Matsuba, Ryoya Yamamoto, Yasuhito Ishigaki,			Hirofumi Nishizono

Case Reports
An Adult Man with Incomplete Amputation of Traumatic Left Upper Arm
with an Aggravated Clinical Course and Unexpected Asthma Attack:An Autopsy Case ………………………………………………………54
						

Shuice Liu, Horyu Hirakawa, Jia Han, Motona Kumagai,
Akihiro Shioya, Sohsuke Yamada

			Naoki Okada, Reiko Fujisawa, Yutaka Saikawa, Hitoshi Sato

Clinical Images: Megakaryocytic Emperipolesis in a Patientwith Myelodysplastic Syndrome ………………………………………85		

KEY WORD INDEX
Vol. 48, 2023

A

L

adult …………………………………………………… (48) 54

lifestyle-related diseases (LSRD) ……………… (48) 11, 21

advanced glycation end-products (AGEs) ……… (48) 11, 21
αSMA …………………………………………………… (48) 43

Manimal experiments …………………………………… (48) 81

maximum standard uptake value …………………… (48) 22

animal protocols………………………………………… (48) 81

megakaryocytes ……………………………………… (48) 85

annuloplasty ring ……………………………………… (48) 65

metabolic tumor volume ……………………………… (48) 22

artificial dermis ………………………………………… (48) 43

mitral valve……………………………………………… (48) 65

asymmetric mandibular prognathism ………………… (48) 76

mouse …………………………………………………… (48) 43

Bmyelodysplastic/myeloproliferative neoplasm ………… (48) 85

basic life support ……………………………………… (48) 33

Nbiodegradable polymer ………………………………… (48) 65

new biomarkers ………………………………………… (48) 21

bronchial asthma ……………………………………… (48) 54
bystander resuscitation ……………………………… (48) 33

CO
obesity ………………………………………………… (48) 54
oral care ………………………………………………… (48) 32

children ………………………………………………… (48) 65

orthognathic surgery ………………………………… (48) 70

collaboration between medical and dental …………… (48) 32

out-of-hospital cardiac arrest ………………………… (48) 33

compression-only resuscitation ……………………… (48) 33

oxidative stress ………………………………………… (48) 54

cytotoxic factor ………………………………………… (48) 11

PD

peak standard uptake value …………………………… (48) 22

decorin ………………………………………………… (48) 43

perioperative oral function management ……………… (48) 32

dispatcher-assisted resuscitation……………………… (48) 33

positron emission tomography

E/computed tomography ……………………………… (48) 22

education and training ………………………………… (48) 81

Remperipolesis…………………………………………… (48) 85

retrospective study …………………………………… (48) 70

HS

healthy life expectancy ………………………………… (48) 21

sagittal split ramus osteotomy (SSRO) ……………… (48) 76

Iinstitutional animal care and use committee ………… (48) 81
intraoral vertico-sagittal ramus osteotomy (IVSRO) …… (48) 76

skin contracture ……………………………………… (48) 43
stability ………………………………………………… (48) 76

Ttotal lesion glycolysis ………………………………… (48) 22

J

toxic AGEs (TAGE) ……………………………… (48) 11, 21

jaw deformity …………………………………………… (48) 70

trauma ………………………………………………… (48) 54

キーワード索引
Vol. 48, 2023

いし医科歯科連携…………………………………………… (48) 29

周術期 ( 等 ) 口腔機能管理 …………………………… (48) 29

け健康寿命………………………………………………… (48) 12

こ口腔ケア………………………………………………… (48) 29

さ細胞障害因子…………………………………………… (48) 1

終末糖化産物 (AGEs) ……………………………… (48) 1, 12
新規バイオマーカー…………………………………… (48) 12

せ生活習慣病…………………………………………… (48) 1, 12

A〜Z
toxic AGEs (TAGE) ………………………………… (48) 1, 12

JOURNAL OF KANAZAWA MEDICAL UNIVERSITYCONTENTS

金医大誌
J Kanazawa
Med Univ

Review
Biodegradable Semi-Rigid Mitral Valve Annuloplasty Ring Designed
for Children ……………………………………………………………… 65
Makoto Ando, Takako Nishino

Original Articles
Characteristic Clinical Features of Orthognathic Surgery Patients
Encountered Over 18year Period–a Retrospective Study ……………… 70

ISSN2436-6994

DECEMBER
2023
Volume 48
Number 2

Miho Hasumoto, Taichi Demura, Hiroyuki Nakano, Yota Yamauchi,
Takao Kato, Eiji Mitate, Satoshi Wada, Noboru Demura

Stability Following Intraoral Vertico-Sagittal Ramus Osteotomy
and Sagittal Split Ramus Osteotomy
for Asymmetric Mandibular Prognathism ……………………………… 76
Miho Hasumoto, Taichi Demura, Satoshi Wada, Yota Yamauchi,
Takao Kato, Eiji Mitate, Hiroyuki Nakano, Noboru Demura

Survey of the Review Process for Approved Animal Protocols
and Feedback to Education and Training ……………………………… 81
Shintaro Matsuba, Ryoya Yamamoto, Yasuhito Ishigaki,
Hirofumi Nishizono

Case Report
Clinical Images: Megakaryocytic Emperipolesis in a Patientwith Myelodysplastic Syndrome ………………………………………… 85
Naoki Okada, Reiko Fujisawa, Yutaka Saikawa, Hitoshi Sato

Published by Kanazawa Medical University Press twice a year
1-1 Daigaku Uchinada, Ishikawa, 920-0293 Japan発行

金 沢 医 科 大 学 出 版 局

920-0293 石川県河北郡内灘町大学1-1

年2回発行