Kohsei Ohtsuki

Individual Variation and Mechanism of Kanamycin Ototoxicity in Rabbits

In order to elucidate the mechanism of individual variation of kanamycin ototoxicity, the possible relationship between the outer hair cell damage induced by kanamycin and the levels of kanamycin in serum or perilymph and of renal damage was investigated in rabbits. No relationship was found between the extent of the outer hair cell damage and the level of kanamycin in the serum or the renal damage. The extent of the outer hair cell damage was closely correlated to the levels of kanamycin in the perilymph. These findings suggest that the individual variations in the outer hair cell damage induced by kanamycin are more closely correlated to the individual differences in the transferability of kanamycin into inner ear than to those in the vulnerability of the outer hair cells or kidneys.

Mechanism of Protective Effect of Fosfomycin Against Aminoglycoside Ototoxicity

The purpose of this study was to clarify the mechanism of the protective effect of fosfomycin (FOM) against inner ear damage induced by an aminoglycoside dibekacin (DKB), when administered concurrently DKB and FOM. Rats were treated with 50 mg/kg of DKB with or without 500 mg/kg of FOM for short-term administration. No significant difference was seen in the serum peak level and in the area under the curve between the group receiving DKB alone and the combined administration group of DKB and FOM. On the other hand, the DKB level in the kidney was significantly lower in the combined administration group than in the group receiving DKB alone. The mechanism of protective effect of FOM against DKB-induced ototoxicity may be considered as follows: FOM inhibits the accumulation of DKB in the kidney and reduces its concentration in the kidney and serum. Consequently, the transferability of DKB into the inner ear is decreased, and finally inner ear damage is reduced.

Evaluation of Ototoxicity of Aminoglycoside Antibiotics in Rabbits

It is generally accepted that the ototoxicity of aminoglycoside antibiotics is gentamicin (GM) > dibekacin (DKB) > kanamycin (KM) > amikacin (AMK) based on the results of animal experiments. However, clinical data reveals that the ototoxicity caused by each of the aminoglycoside antibiotics does not coincide with the ototoxicity in the animals. The present study was intended histopathologically for comparative evaluation of above-mentioned antibiotics using rabbits. The ototoxicity was GM > DKB > KM > AMK with the dose of 100 mg/kg, which coincide with many of the conventional reports on animal experiments. However, with the dose of 50 mg/kg, the order was GM > AMK > KM > DKB. With the dose of 30 mg/kg, hardly any differences were noted between the ototoxicity of GM and that of AMK. It was found out that the evaluation of the ototoxicity of drugs in high doses does not always correspond to that of lower doses. Therefore, the ototoxicity should be evaluated in strict consideration of dose of drugs. Usually, the doses of drugs used in the ototoxicity studies with animals are more than 10 times higher than those used clinically. Consequently, problems still exist in infering the ototoxicity of drugs in humans directly from the results obtained from animal experiments.

Relationship between ototoxicity of aminoglycoside antibiotics and their transferability into inner ear fluids.

The purpose of this study is to clarify the question whether the difference of severity of ototoxicity induced by the aminoglycoside antibiotics depends on the difference of quantity of transferability into inner ear. Aminoglycoside antibiotics (tobramycin, kanamycin, netilmicin and ribostamycin) were injected for 30 consecutive days to rabbits. The relationship between the severity of hair cell damage and concentration of antibiotics in perilymph was investigated. The drug concentration in the perilymph was determined by the bioassay method, and using the surface preparation technique the hair cell damage was observed under a phase contrast microscope. It was concluded that the difference of severity of ototoxicity induced by the aminoglycoside antibiotics is due to the difference of their own toxicity to hair cells but not to the difference of their transferability into the perilymph.

Antitumor Effect of Cisplatin Combined with Fosfomycin

The influence of Fosfomycin (FOM) against the antitumor effect of Cisplatin (CDDP) was investigated using ddY-strain mice. Each mouse was inoculated with Ehrlich carcinoma cells (2 x 106 cells/0.2 ml) subcutaneously. One group was given daily doses of 1.0, 1.5 or 2.0 mg/kg/day of CDDP for 5 consecutive days, and the other one was given 5.0, 7.5 or 10.0 mg/kg of CDDP for only one day. Both groups were treated with or without 300 mg/kg/day of FOM for consecutive 5 days. The tumors were weighed on day 14. There was no difference of the tumor weight between the group of CDDP alone and the one in combination with FOM. It is concluded that this combined administration does not influence the antitumor effect of CDDP.

Vascular Leiomyoma of the Nasal Cavity

A case of vascular leiomyoma of the nasal cavity is reported. The patient was a 59-year-old male who complained of intermittent nasal bleeding in his thirties. A spherical tumor was seen on the right inferior turbinate. He was treated surgically via the transmaxillary aproach under general anesthesia. The histopathological findings revealed vascular leiomyoma.

A Statistical Survey of Patients Treated in Our Clinic during the Past 28 Years

This is a statistical survey of patients treated in the Department of Otorhinolaryngology, Fukushima Medical College, from August 1957 to December 1984.1) The total number of patients was 6002 and that of diseases treated was 6153.2) The locations of the diseases were: 1140 in the ear (18.5% of all diseases), 1962 in the nasal cavity and paranasal sinuses (31.9%), 1394 in the pharynx (22.7%), 531 in the oral cavity (8.6%), 772 in the larynx (12.5%), 249 in the trachea and esophagus (4.1%), 105 in the face and neck and other areas (1.7%).3) The number of cases of chronic purulent otitis media and chronic paranasal sinusitis has decreased greatly.4) Of the diseases in the oral cavity 22.8% were cancer of the tongue with a male predominance.5) There were 40 parotid tumors, 34 benign and 6 malignant. The incidence of parotid tumor has increased somewhat since 1978.6) In the trachea and esophagus, the most prevalent disease was foreign bodies (72% of all disease in the trachea and esophagus). The incidence of foreign bodies in the trachea was highest in children under 4 years of age, and in the esophagus it was high in both children and aged people.

Scanning Electron Microscopic Observations of the Rabbit Cochlea

蝸牛有毛細胞 と蓋膜 との接続 の知識 は,聴 覚受容の メカニズムを理解 す る上で重要 であ り,近 年,蓋 膜 に 聴毛の先端が陥入 して生 じた小孔,つ ま りimprint についての走 査電顕的観察 が,ヒ ト,サ ル,猫,モ ル モ ット等 で報告 されて いる。今 回,我 々は,家 兎蝸牛 を,特 に蓋膜 のimprintを 中心に走査電顕で観察 し モル モ ットのそれ と比較検討 したので報告 した。 実験材料 白色家兎及 びプ ライエル反射 正常の ハー トレイ系 モ ル モッ トを使用 した。 実験方法 断頭後,す みやかに内耳 を2%グ ル タール アルデ ヒ ドにて固定,さ らに1%オ ス ミウム酸にて2重 固定を 行ない,コ ルチ器 を とりだ した後に上昇エ タノール列 にて脱 水 し,さ らに臨界点乾燥法にて乾燥 を行 なった 。 試料 は,JFC1100型 イオンスパ ッタ リング装置 にて 蒸着 を行な った後,JSM-35C走 査電子顕 微鏡にて観 察 した。 実験結果 家兎 の内 ・外有毛細胞の聴 毛 はモル モ ットと比較 し て基本的 に差異 は認 め られなか ったが,家 兎では内有 毛細胞 の過剰細胞が モルモ ッ トに比べ て比 較的数多 く 認 め られ た。 図1(a)は,第1回 転後半の家兎蓋膜 の裏 面で,外 有 毛細胞 のimprint`つ ま り外有毛細胞の聴毛 に相 当 す るW型 の くぼみが3列 に配列 してい るのが観察 され た。図1(b)は,そ の強拡大像で,蓋 膜 の裏面 は線維 に 富 んでお り,外 有毛細胞聴 毛の中で最 外側列 の最 も長 い聴毛 によって生 じたと考え られ る1列 のimprint が み られ た 。図2(a)及 び(b)は,第1回 転 の モ ル モ ッ ト 蓋 膜 のimprintで,こ の よ うに家 兎 及 び モ ル モ ッ ト に み られ たimprintは,す べ て1列 で,い わ ゆ る single imprintを 呈 して お り,川 端 らが ヒ ト蓋膜 で報 告 して い る様 なmultiple imprintは 観 察 さ れ な か った 。 図3は,第1回 転 前 半 の家 兎 のimprintで,聴 毛 先 端 の蓋 膜 へ の は ま り込 み が 少 な く,比 較 的 浅 い くぼ み と して観 察 され た 。 図4は,第2回 転 前 半 のimprintで,深 く陥 凹 して お り聴 毛 先 端 の 蓋膜 へ の は ま り込 みが 深 くな って い る こ とが 考 え られ た 。 しか し, 頂 回転 で はimprintは 観 察 され な か っ た 。 これ らの よ うに大 部 分 の もの で は平 坦 な 蓋 膜 にimprintが み られ た が,家 兎 の中 に は川 端 らが ヒ トで 報 告 して い る よ うにimprintに 沿 って 蓋膜 の 隆 起 す るの が み られ た 。 図5(a)は,第2回 転 の 家兎 蓋膜 のimprintで 第 1列 目 の外 有 毛 細 胞 聴 毛 のimprintの 存 在 す る部位 が 相 当隆 起 して い るの が み られ た 。 これ を拡 大 す る と 図5(b)の 如 く,そ の 隆 起 に 沿 ってimprintの 小 孔 が 明 瞭 なW型 に 存 在 す るの が 認 め られ た。 ま た,Hensens stripeと 外 有 毛 細胞 第1列 目 の 聴 毛 に相 当す るimprintと の 間 に は,星 野 が ネ コで 報 告 して い る よ うな 内 有 毛 細胞 の聴 毛 に相 当 す る様 な くぼ み は観 察 され な か っ た 。 考 按 家 兎 蓋膜 のimprintは,基 底 部 で は浅 くな って お り,第2回 転 では 深 い もの が み られ,さ らに,頂 回転 に はimprintが 観 察 され な か った こ とな どが ら,