Ceftazidime (CAZ, SN401) は新しい半合成セファロスポリン系抗生剤で, 今回本剤の臨床効果を得るために122例の尿路性器感染症患者に本剤が投与された。111例の複雑性尿路感染症患者の内訳は慢性腎盂腎炎12例および慢性膀胱炎99例であり, 11例の性器感染症患者の内訳は急性副睾丸炎10例および急性前立腺炎1例であった。複雑性尿路感染症における薬効評価の判定はUTI研究会の薬効評価基準に基づいて行なわれ, 性器感染症における薬効評価の判定は発熱, 局所の疼痛および腫脹に対する効果に基づいて投与3日後および5日後に行なわれた。
投与方法については, 本剤500mgが静注により1日2回5日間投与された。複雑性尿路感染症患者における薬効評価は著効28例, 有効63例, 無効20例で, 総合有効率は82.0%であった。細菌学的効果については, 本剤の投与によりグラム陰性桿菌-特にSerratia marcescens, Pseudomonas aeruginosa, Escherichia coli, Preteus vulgaris, Enterobacter cloacae-の大部分が消失した。一方, Stroptococcus spp.およびFlavobacterium odoratumの約半数は, 本剤投与後も尿中に存続した。尿中分離菌に対するMICについては, 本剤はP.aeruginosaを含む多くのグラム陰性桿菌に対して良好な抗菌活性を有していた。性器感染症患者に対する本剤投与3日後の臨床効果は著効5例, 有効6例で, 投与5日後では著効8例, 有効3例となっており, 総合有効率はそれぞれ100%であった。
副作用としての症状は2例に認められ, 1例は薬疹, 1例は上腹部痛と軟便であった。なお, 本剤投与により明らかに悪化したと考えられる臨床検査の変動は認められなかった。

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新しく開発された注射用半合成セファロスポリン系抗生剤cefotaxime (CTX) の1gを, 種々の程度の腎機能を有する30例に筋注した際のCTXおよびdesacetyl CTXの血清中および尿中濃度を測定した。濃度測定は高速液体クロマトグラフイーにより行ない, 薬動力学的解析はonecompartment open modelに従った。なお腎機能の指標としては, 24時間内因性クレアチニンクリアランス (Ccr) を用い, 各種薬動力学的パラメータとの関連性について検討した。腎機能正常例におけるCTXの最高血清中濃度は。筋注30分後に得られ平均26.3μg/mlで, 血清中濃度半減期は平均0.86時間と計算された。また消失速度定数 (Kel) とCcrとの間には有意の相関関係が認められ (P<0.001), 回帰直線方程式Kel=0.2451+0.0050 Ccrが得られた。血清中濃度半減期は, 腎機能の低下に伴い延長したが, その延長の程度は他の同系抗生剤に比し軽度であり, desacetyl CTXへの変化に由来するものと考えられた。腎機能正常例における筋注後24時間までのCTXの尿中回収率は平均51.7%, desacetyl CTXは平均25.6%であり, いずれも腎機能の低下に伴い回収率は減少したが, desacetyl CTXの減少率はCTXに比し軽度であった。なお3例の血液透析患者の検討で, CTXおよびdesacetyl CTXはともに透析性が認められた。

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抗緑膿菌作用を有する注射用半合成セファロスポリン系抗生剤cefsulodin (CFS) 250 mgを種々の程度の腎機能を有する18例に筋注した際の血澗中濃度および尿中排泄盤を測定した。濃度測定はPseudomonas aeruginosa NCTC 10490を検定菌とする薄層カップ法にて行ない, 薬動力学的解析はone-compartment open modelに従った。なお腎機能の指標としては, 24時間内因性クレアチニンクリアランス (Ccr) を用い, 各種薬動力学的パラメータとの関連性について検討した。腎機能正常例における最高血清中濃度は1時間後に得られ, 平均9.1μg/mlであり, 血清中濃度半減期は平均1.22時間と計算され腎機能の低下とともに延長した。また消失速度定数 (kel) とCcrとの間には有意の相関関係が認められ (P<0.01), 回帰直線方程式kel=0.0584+0.00556×Ccrが得られた。腎機能正常例における筋注後6時間までの尿中回収率は平均69.4%で腎機能の低下に伴い減少した。腎機能障害ことに高度な障害を有する患者に本剤を投与する際には, 投与量, 投与間隔の調節が必要であると考えられた。

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cefotiam (CTM) は, 新しい合成セファロスポリン系抗生剤であるが, 本剤500mgを種々の程度の腎機能を有する11例に筋注した際の血中および尿中濃度を測定し, 薬動力学的解析はonecompartment open modelに従った。なお腎機能の指標としては, 24時間内因性クレアチニンクリアランスを用いた。その結果, 以下の結論を得た。1) 血中濃度は腎機能の低下に伴い上昇した。2) 腎機能正常者の血中濃度半減期は平均1.0時間と計算され, 腎機能の低下に伴い延長した。3) 腎機能正常者の筋注後6時間までの累積尿中回収率は平均44.8%で, 腎機能の低下に伴い減少した。4) 腎機能と分布容積との間には有意の相関関係が認められた。5) 腎機能と血清クリアランスとの間には有意の相関関係が認められた。

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新しく開発された注射用半合成セファロスポリン系抗生剤Ceftizoxime (CZX) の500 mgを, 種種の程度の腎機能を有する33例に筋注した際の血清中および尿中濃度を測定した。濃度測定はBacillus subtilis ATCC 6633を検定菌とする薄層ディスク法で行い, 薬動力学的解析はone-compartment open modelに従った。なお腎機能の指標としては, 24時間内因性クレアチニンクリァランス (Ccr) を用い, 各種薬動力学的パラメータとの関連性について検討した。腎機能正常例における最高血清中濃度は, 筋注30分後に得られ平均14.7μg/mlで, 血清中濃度半減期は平均1.45時間と計算された。また消失速度定数 (Kel) とCcrとの間には有意の相関関係 (P< 0.001) が認められ, 回帰直線方程式Kel=0.0202+0.00483 Ccrが得られた。腎機能正常例における筋注後6時間後までの尿中回収率は平均77.6%で, 腎機能の低下に伴い減少した。腎機能障害, ことに高度な障害を有する患者に本剤を投与する際には, 投与量, 投与間隔の調節の必要があるものと考えられた。

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Cefamandole sodium (CMD) は, 新しく開発された注射用セフェム系抗生剤である (Fig.1)。本剤は, グラム陽性菌に対する抗菌力を劣化させることなく, グラム陰性菌に対渉る抗菌力を増強し, そのため広い抗菌スペクトラムを有するのが特徴である1吻。本剤の基礎的, 臨床的評価は第26回日本化学療法学会の新薬シンポジウムでなされ, 抗菌剤としての有用性がほぼ確認されている5)。
我々は, 尿路感染症 (以下, UTI) のうち難治性と言われる複雑性UTIに対する本剤の有効性,安全性及び有用性をCefmetazole sodium (CMZ)(Fig. 1) を対照薬として, 二重盲検法により比較検討したのでその成績を報告する。

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Cefsulodin (SCE-129, CFS), a new cephalosporin derivative synthesized in Japan, was evaluated experimentally and clinically. The results obtained were as follows:
1) Minimal inhibitory concentrations of CFS, sulbenicillin (SBPC) and gentamicin (GM) were determined against 18 clinical isolates of Pseudomonas aeruginosa. CFS was more active than SBPC or GM.
2) CFS was administered intramuscularly at a single dose of 250 mg to 2 male healthy volunteers and 6 patients with normal or impaired renal function. The serum and urinary concentrations were assayed by cup method during 6 hours after administration. The serum concentrations showed peak at 1 hour after injection in all cases. The half-life of CFS was calculated for 1.3 hours in the volunteers, and became prolonged as the renal function fell.
Seventy-six per cent of administered dose was excreted in the urine during the first 6 hours of administration.
3) Twelve patients with Pseudomonas infection of urinary tract were given CFS intramuscularly in daily dose of 500 mg twice a day for 7 days. The clinical results obtained were excellent in 2 cases (16 7%), good in 1 case (8.3%) and poor in 9 cases (75.0%).
4) No marked side effects were observed.

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新しく開発された注射用半合成セファマイシン系抗生剤Cefotetan (CTT, YM09330) の500mgを, 種々の腎機能を有する49例に静脈内投与した際の血清中および尿中濃度を測定した. 濃度測定は, E.coli NIHJを検定菌とするbioassayとともに, 尿については高速液体クロマトグラフィーによる本剤とそのtautomerの分離定量も行った. 腎機能の指標としては, 24時間内因性クレアチニン・クリアランス (Ccr) を用い, 薬動力学的解析はtwo compartmentopen modelにしたがった。本剤投与直後の血清中濃度は, 腎機能障害程度と関係なくほぼ一定であった。しかしβ-phaseでは, 腎機能の低下に伴い遷延化する傾向がみられ, 消失速度定数 (t1/2およびβ) とCcrとの間に有意の直線関係が認められた。また腎機能正常例の血清中濃度半減期 (t1/2β) は平均3.0時間で, 腎機能の低下に伴い延長したか, その延長の程度は従来の同系抗生剤に比し軽度であり, 血液透析例におけるt1/2βは平均13.1時間と計算された. また5時間の血液透析によりt1/2βの約40%の短縮が認められた. 腎機能正常例における本剤の投与後24時間までの尿中回収率は平均83.3%で, 腎機能の低下に伴い減少した。なお本剤の尿中tautomerの存在比率は4～10%の範囲内でばらつき, 排泄量に関係なく尿中 Cefotetanの大部分は変化せす, ごく一部がtautomerに変化するものと考スられた。

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Forty cases of adrenal diseases, including 20 cases of primary aldosteronism, 8 cases of Cushing's syndrome, 7 cases of adrenogenital syndrome, and 5 cases of pheochromocytoma, have been treated in our department during the past 10 years until the end of 1974.
In order to localize adrenal tumors, some combination of retroperitoneal pneumography, tomography, adrenal venography, radioisotope photoscanning and abdominal aortography was used.
The results obtained were as follows:
1. Using retroperitoneal pneumography combined with tomography, 22 of 30 cases (primary aldosteronism, 18 cases; Cushing's syndrome, 7 cases; adrenogenital syndrome, 3 cases; pheochromocytoma, 2 cases) were diagnosed correctly (73% accuracy).
2. Adrenal venography showed a tumor lesion in 15 of 18 cases (primary aldosteronism, 11 cases; Cushing's syndrome, 5 cases; adrenogenital syndrome, 2 cases).
3. Radioisotope photoscanning, using ¹³¹I-19-iodocholesterol, of the adrenal and abdominal aortography revealed a tumor contour in all of the 5 cases (primary aldosteronism, 4 cases; Cushing's syndrome, 1 case) and in all of the 3 cases performed (pheochromocytoma, 3 cases). The radioisotope scanning was most useful in localizing adrenal cortex tumors.

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Prostatic cancer now is a problem of increasing importance in Japan. Various types of treatment for prostatic cancer have been tried and evaluated so far, yet hundreds of patients die every year because of difficulty in its early diagnosis. Although most urologists have the opinion that radical prostatectomy may be the only cure for prostatic cancer, it is also a fact that complications noted in the radical prostatectomy sometimes give more trouble to the patient than the disease itself. Transurethral resection of course is not a radical measure, but a conservative one to relieve obstruction of the lower urinary tract caused by the condition. This paper is given to report our late experiences of thirty-four transurethral resections which were performed in twenty-eight patients of prostatic cancer at the Jikei University Hospital and the Iwate Medical University Hospital, from Februafy 1961 to January 1965.
Of the total twenty-eight patients, twenty-one patients (75per cent) were diagnosed as incurable cancer upon initioal examination, classified as group C or D by Kaufman's classification. The remaining seven patients (25per cent) were classified as group A or B. These cases could be called as curable cancer by radical prostatic surgery, but transurethral resection was chosen because of patient's senility or poor general condition. Obstructive urinary symptoms were the chief complaints in the majority of the patients (25 patients: 89per cent).
The amount of tissue resected weighed 10 grams on the average, oaring from 1 to 42 grams, and the time needed for the resecting procedure was 42 minutes on the average, oaring from 5 to 65 minutes. Satisfactory relief of the obstructive urinary symptoms was obtained in all the cases.
Urigal (cytal) was used as an irrigating medium in all the cases, and no remarkable change was noted in the postoperative serum electrolytes.
The blood loss during the resecting procedure was about 134cc, macroscopic hematuria disappeared within two to three days and indwelling catheter was removed on the 3rd postoperative day on the average.
Endocrine therapy, either by the administration of antiandrogenic hormone or by intracapsular orchiectomy or by a combination of the two has been done in all the patients.
Of the total twenty-eight patients, seventeen patients (61per cent) have been known to be alive and continued to be under our observation. Nine patients (32per cent) had died either by the disease (7 patients) or by postoperative complications (2 patients). No communication was obtained postoperatively from the remaining two cases.
Of the seventeen patients, in each of whom combined therapy of transurethral resection and anti-androgenic hormone was performed, nine patients were noted to have been surviving up to Jauary 1965, that it for more than 14 months (5 to 42 months) postoperatively on the average. Of the nine patients, in whom intracapsular orchiectomy was performed along with transurethral resection and also administration of antiandrogenic hormone, eight patients were noted to have been surviving for more than 24 months (5 to 45 months) after the operation on the average.
Fourteen patients who were classified as group A, B or C upon initial examination revealed apparently better survival rate (86per cent) than the twelve patients classified as group D (42per cent).
Taking the above mentioned results into consideration, the authors assumed that transurethral resection is a desirable operation for relief of obstructive urinary symptoms noted in prostatic cancer.
Combined therapy of administration of antiandrogenic hormone together with intracapsular orchiectomy is recommended.

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新しく開発された注射用セフェム系抗生剤Ceftazidime (CAZ) の500mgを, 健康成人ポランティア7例を含む種々の程度の腎機能を有する計39例に静注した際の血漿中および尿中濃度を測定した。CAZの濃度測定は, Proteus mirabilisATCC 21100を検定菌とし, 培地としてDST agarを用いたthin-layer paper disk 法にて行った。腎機能の指標としては, 24時間内因性クレアチニンクリアランス (Ccr) を用い, 薬動力学的解析はtwo-compartment open modelに従った。本剤静注後のβ-phaseにおける血漿中濃度は, 腎機能の低下に伴い遷延化する傾向がみられ, 消失速度定数 (K_e1 およびβ) とCcrとの間には有意の相関関係 (いずれも P<0.0001) が認められた。また, 腎機能正常者のβ-phaseにおける血漿中濃度半減期 (t_1/2β) は平均1.67時間で, 腎機能の低下に伴い双曲線的に延長し, Ccr 10ml/min 未満の症例におけるt1/2β は平均14.37時間であった。なお, 血液透析患者6例の血漿中濃度は, 血液透析により明らかに低下した。腎機能正常者における本剤の24時間累積尿中回収率は平均89.6%と高かったが, 腎機能の低下に伴い低下した。以上より, 高度の腎機能障害を有する患者に本剤を投与する際には, 高い血中濃度持続による副作用発現予防の観点からも投与方法の調節の考慮が必要と考えられた。

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Using a plasma recalcification time test and fibrin plate assay system, saline and 2M KSCN extracts from in vitro cultivated KK-47 cells (130 passages) possessed minimal thromboplastic and fibrinolytic (tissue plasminogen activator) activities, respectively. The saline extracts exhibited a slight urokinase inhibitory activity (0.4 CTA units/ml) as well.
Fibrinolysis autography showed areas with less lysis of fibrin related to the cells on plasinogenrich fibrinogen.
No thromboplastic and fibrinolytic activities were observed in any of culture supernates of KK-47 cells (76, and 130 passages) using serum-free medium (Ham F 12+2% gelatin), for up to 36 hours.
Possible relationships between the tumor growth and the activities are discussed.

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Purpose of the study.
In the urethra of the woman occurs unendurable pains of unknown origin, such as urodynia and feeling of strangury. In an attempt to solve the problems, the structure of the tissue is found to be so complicated that a considerable amount of the pains might be originated from the anatomical and histological structure. That is, the short urethra in the woman shows a variety in its strusture according to localization, especially having a number of so-called para-urethral ducts or folds in its anterior portion: this state is rather more complicated than that of the man. The present study is performed to clarify these unanswered problems.
Method
The total urethra was removed from cafuistic corpse of adolescent and adult women taking care of not hurting the original form, embedded into paraffin and sectioned in three directions. 1. Transverse section, 2. Sagittial section, 3. Horizontal section. After many kinds of stainings were applied to these sections, details of the histological structure of the urethra in the woman were observed together with the informations of mucous epithelium of the urethral cavity, the fold formation, and the number, direction and morphology of the para-urethral ducts.
Results
1) Morphology of the urethral cavity and its variation. The urethra in the woman is comparatively broad. Usually it is in contracted condition, forming natural folds. Only at micturition it becomes nearly cylindrical,
a.. The cavity appears longitudinal or polylongitudinal around the opening, but changes to be transverse at the posterior portion.
b.. Near the part of 1-1.5cm away from the opening there are polymorphic contracted fold formations; of mushroomshape or crab-shape.
c.. Near the part of 2-2.5cm away the cavity takes a shape of butterfly in many cases.
d.. Near the part of 2.5-3cm away it becomes like an upperly prominent semilune or a straight line.
e.. At the inner part than 3cm away it is of an irregular form with a little larger interspace, becoming so-called neck of the urinary bladder and reaches the bladder. At the same time, according to the examination of the horizontal section, it is found that the urethra is broad at the lower wall and prominent at the upper part.
2) Para-urethral duct
a.. Around the opening there are so-called Skene's duct and similar ducts. Many case offer a number of large and small ducts at the margins of th external lip with the depression of mucous membrane. Near the part of 0.5cm away from the opening there exhibit also many ducts.
b.. Near the part of 1-1.5cm away, the urethra takes shapes of irregularly transverse form, and deep fold formation like a crab or several butterflies. Surrounding this contricted urethra, large and small duct cavities occur at least more than ten, usually more than thirty. If all of them, adding small branches at the end are altogether calculated, the number may be several decades or countless.
c.. Near the part of 2cm away, the urethra becomes in most cases of a butterfly-shape, consequently having a deep fold formation, while the duct number decreases suddenly into a few or even undetectable in some cases.
d.. Near the part of 2.5-3cm away, the urethra becomes semilunar or of upperly prominent straight line. Most cases contain a few ducts, which occur especially at right and left sides of the urethra in usual cases.
e.. At the part of more than 3.5cm away, as the urethra approaches to the inner meatus urinarius and the urinary bladder, so the urethral cavity exhibits an enlargement or lenticular form.
The ducts are few or not visible in some cases.
3) The fold formation in the urethra.
There is the fold formation in the urethra. The most remarkable and deepest localization appears near the part of 1-1.5cm or 2cm away from the opening: the contracted part of the irregular petal-shape, the parts of the crab-shape and butterfly-shape; the both sides of the straight line part at middl

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Soft-tissue shadow outline of the bladder can be seen in some cases of bladder outlet obstruction. An attempt has been made to determine the significance of the soft-tissue shadow by correlating cystogram with histological findings of the bladder detrusor muscle not only in experimental animals but in clinical cases.
Firstly, the soft-tissue shadow could be demonstrated in some cases of the bladder neck obstruction by means of excretory cystogram, retrograde cystourethrogram and double contrast cystogram, the last one being proved to be the best method to detect the soft-tissue shadow.
Secondly, the finding of the soft-tissue shadow appeared to betray the existence of bladder neck obstruction during the compensatory phase of the bladder detrusor muscle, while in the decompensatory phase soft-tissue shadow could not be demonstrated in any cases of bladder neck obstruction.
Thirdly, histological studies clarified that bladder wall showed a hypertrophy of the detrusor muscle and a proliferation of the stromal tissues in the positive case of soft-tissue shadow.
In conclusion, it is not so difficult to find the urinary tract obstruction in advanced cases. However, compensatory detrusor hypertrophy demonstrates soft-tissue shadow by the roentgenography, which serves to diagnose early bladder neck obstruction without any subjective complaint or objective disturbance.

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16β-Ethyl-17β-hydroxyestr-4-en-3-one (oxendolone) (1), a new antiandrogen, was synthesized starting from dehydroepiandrosterone (2). 3β-Acetoxy-16β-ethylandrost-5-en-17β-ol (3), prepared from 2 by stereospecific introduction of 16β-ethyl substituent, was converted into 3β, 17β-diacetoxy-5α-chloro-16β-ethyl-androstan-6β-ol (5) by acetylation and then chlorohydrination. Treatment of 5 with lead tetraacetate gave 3β, 17β-diacetoxy-5α-chloro-16β-ethyl-6β, 19-oxidoandrostane (6) in 96% yield. 6 was transformed into 17β-acetoxy-16β-ethyl-6β, 19-oxidoandrost-4-en-3-one (8) by two steps. Reductive cleavage of an oxido bond of 8 with zinc followed by oxidation with pyridinium chlorochromate yielded 17β-acetoxy-16β-ethylandrost-4-ene-3, 19-dione (10) in 75% yield. Treatment of 10 with sodium hydroxide followed by acid hydrolysis gave 1 in good yield.

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注射用半合成セファロスポリン系抗生剤Cefotaximeの健康成人における体内動態および尿路感染症および男子性器感染症に対する臨床効果について検討した。健康成人男子5例に本剤1g点滴静注時の血中濃度は, 点滴終了時の1時間値が最高でbioassayで平均54.1μg/mlであり, 以後比較的速やかに下降した。なおCefotaximeのdesacetyl体であるRU 628は高速液体クロマトグラフィーで測定したが, 2時間値が最高で74μg/mlであった。また0-6時間までのCefofaximeおよびRU628の累積尿中回収率は51.3%および13.5%であった。複雑性尿路感染症28例の臨床効果は, 著効6例, 有効13例, 無効9例で, 総合有効率は67.9%であった。急性男子性器感染症4例の臨床効果は, 著効2例, 有効2例で, 有効率は100%であった。副作用として, 1例に本剤によると考えられるGOT, GPTの上昇が認められたが, 投薬終了後速やかに正常値に復した。

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AB-206, a new synthetic antibacterial drug with similar chemical structure to nalidixic acid, was evaluated experimentally and clinically in our department. The results were as follows:
1) Concentrations of AB-206 after oral administration of 250 mg were determined in serum and urine of 6 male healthy adult volunteers (3 fasting cases and 3 non-fasting cases). The mean peak concentration in serum was 2.5μg/ml at 1 hour in fasting cases and 2.0μg/ml at 4 hours in non-fasting cases following administration. And the mean urinary recovery during the first 6 hours of administration was 2.2% in fasting cases and 2.6% in non-fasting cases.
2) Thirty-seven patients with urinary tract infections (25 of acute simple cystitis, 10 of chronic complicated infections and 2 of acute complicated cystitis) were given AB-206 250 or 500mg four times a day for 5 days. And the clinical results obtained were excellent in 17 cases (45. 9%), good in 9 cases (24. 3%) and poor in 11 cases (29. 7%).
Three patients exhibited side effects: One with slight epigastralgia, one with dizziness, and one with nausea and headache.
3) It was found that AB-206 was more active than nalidixic acid and piromidic acid against Escherichia coli isolated from urine specimens of patients with urinary tract infections.

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新しく開発されたアミノ配糖体系抗生剤であるNetilmicinを慢性複雑性尿路感染症28例 (慢性腎孟腎炎6例および慢性膀胱炎22例) に使用し, 臨床効果を中心に検討した。投薬方法は, Netilmicin100mgを1日2回筋注し, 5日間投薬終了後に効果を判定した。28例の総合臨床効果は, 著効11例, 有効5例, 無効12例で, 有効率57.1%であった。また本剤投薬前に28例の尿中からEsoherichiacoli9株など計39株が分離され, 本剤投薬後31株 (79.5%) が消失した。投薬後出現菌としてFlabobacterium2Spp.3株など計11株が認められた。副作用に関しては, 自他覚症状および臨床検査値とも異常を呈した症例は認められなかった。

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新しく開発された抗生剤6059-Sを尿路感染症および男子性器感染症の計21例に使用し臨床効果を中心に検附した。
副作用のため投薬を中止した1例を除く慢性複雑性尿路感染症16例の臨床効果は著効1例, 有効6例, 無効9例であり, 有効率は43。8%であった。急性男子性器感染症4例の臨床効果は著効3例, 有効1例であり有効率は100%であった。副作用は4例に認められ, 発疹1例, GPTおよびアルカリフォスファターゼの上昇1例, GPTの上昇1例, BUNの上昇1例であった。

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