Kazuo Uede

In vitro prediction of aminoglycoside ototoxicity

SummaryThe first step by which a basic aminoglycoside (AG) causes ototoxicity is thought to be electron binding to such acidic substances as phosphatidylinositol diphosphate and acidic glycosaminoglycans (AGAGs). We studied the competitive binding ability of AGs and basic dyes to AGAG in order to determine if this meachanism was indeed responsible for ototoxicity. The negative charge of heparin was the strongest among the AGAGs examined when the molar ratio of AG to AGAG was small. Toluidine blue was a better basic dye than acridine orange, methylene blue, alcian blue, or neutral red. After we mixed toluidine blue, heparin and an AG, the absorbance of free toluidine blue was measured at 625 nm. The difference in the free dye released by the well-established AG showed a fairly good correlation with the ototoxic activity found in vivo. However, the predicted ototoxicities of newly prepared AGs were greater than estimated when testing their effects on experimental animals. The basicity of AGs will determine their binding affinities to cochlear hair cell membranes and is an important factor in predicting ototoxicity.

Interaction of polyanion against kanamycin ototoxicity.

We studied whether interference of the electron bindings between kanamycin (KM) and the outer plasma membranes of the hair cells with polyanion such as heparin can reduce ototoxicity. In a short course experiment, KM 200 mg/kg/day was injected intramuscularly 23 times with or without 1 U or 0.5 U of heparin/g/day differently to 22 guinea pigs. The reducing effect of heparin against KM ototoxicity was significant from a comparison of the N1 threshold obtained by the cochleogram. The number of surviving outer hair cells in the heparin groups was significantly greater in the third turn than in the group given KM alone. A long course experiment in which 50 injections of KM with or without 0.5 U of heparin were given intramuscularly to 16 guinea pigs revealed from the pinna reflex, cochlear microphonics and cell counting that heparin could reduce ototoxicity slightly at an early stage or before reaching crucial accumulation.

Changes of ground substance in the inner ear in Alloxan diabetic mice

SummaryOne of the important substances in the ground substance is acidic glycosaminoglycans (AGAGs). Changes of AGAGs in the inner ear and in other organs were investigated using alloxan diabetic mice in order to contribute to the understanding of diabetic hearing impairment. In the diabetic group, gradual increases of AGAGs were observed in each tissue. On the 60th day after alloxan injection, AGAG values were increased 3.5-fold in the cochlea, 2.5-fold in the brain, 13-fold in the liver, twofold in the kidney, and fivefold in the pancreas compared with the control values. It is interesting to note that both the cochlea and pancreas showed continuous increases of AGAGs.

Statistical study of ear surgery from 1977 to 1989.

Surgery, primarily tympanoplasty, was performed on 1051 ears from April 1977 to March 1989. Two-thirds of the patients were aged 30 to 60. There was no sex difference in any age group. Chronic otitis media was observed in 45.2% and cholesteatomatous otitis media in 33.7%. Including the ears that needed reoperation or secondary operation, 931 ears (88.6%) were operated on for problems related to chronic otitis media; tympanoplasty was performed in 885 of them. In the ears with chronic otitis media, operation was type I in 60.8% and modified type III in 16.5%. In ears with cholesteatomatous otitis media, operation was type Tin 30.7% and modified type III in 30.4%.Hearing was good in 86.9% after type I operation, in 77.2% after modified type III operation, and in 45.3% after modified type IV operation. No difference was observed in the columellae used other than the cartilage and auditory ossicles. Recurrence was observed frequently in the ears followed for a long time after posterior walll preserving operations for cholesteatomatous otitis media.

Cholesterol Granuloma in the Posterior Ethmoid Sinus

A case of cholesterol granuloma in the ethmoidal sinus is reported. The patient was a 44-year-old male whose chief complaint was visual disturbance. Visual acuity improved transiently at the early postoperative day, but his visual impairment could not be healed completely. Although CT was one of the best method for diagnosis, conventional methods, tomography and Rheses method, were also useful for early detection and diagnosis. The cholesterol granuloma was thought to be caused by hemorrhage. However, closed cavity was also an important facter for the development of cholesterol granuloma.

Long-term results of selective vidian neurectomy for allergic rhinitis.

Vidian neurectomy is the most effective treatment of allergic rhinitis with dominant symptoms of paroxysmal sneezing and rhinorrea. Although these symptoms disappear dramatically after this operation, most patients usually suffer from prolonged xerophthalmia. Therefore, we devised a method which reduces allergic symptoms and does not cause dry eyes on the basis of studies reported by Takahashi (1973) and Nomura(1971).Using this procedure we operated on 55 patients who had allergic rhinitis with persistent symptoms in spite of conservative therapies including desensitization. The ages of the patients were between 15 and 47. The average period of post-operative observation was 2 years and 4 months.The maxillary antrum is opened as in the Caldwell-Luc method and the posterier wall removed. The periosteum of the pterygopalatine fossa is then peeled off andpressed laterally. The vidian canal is reached subperiosteally above the sphenomaxillary sur face of the sphenoid. In front of the canal, post-ganglionic fibers (post-nasalbranch) enter medially through the sphenopalatine foramen with the sphenopalatine artery. This branch is sectioned after electrocauterization subperiosteally. About 90percent patients were relieved of symptoms with no decrease of lacrimation. There were no serious complications.

Chondroma of maxilla - A case report.

A five-year-old female visited our hospital because of nasal obstruction and epiphora. The right nasal cavity was occupied by a soft gray tumor. After total resection of the tumor piece by piece, it was considered that the tumor originated from the lateral wall of the right nasal cavity and spread to the right maxillary sinus, ethmoid sinus, and nasal cavity. Histological examination revealed a benign Chondroma. As Chondroma tend to exhibit sarcomatous changes, long-term follow-up is essential.

Mass Examination for Early Detection of Glottic Cancer

Mass examination of laryngeal cancer has been attempted only in a few area in this country. From May to July in 1984, our mass examination for early detection of glottic cancer and other diseases of the vocal fold was performed in co-operation with eight health centers, twenty four E. N. T. clinics and a local press in Fukui prefecture.Six hundred and eleven patients, who complained of hoarseness, underwent the examination. They consisted of 343 males and 268 females. Age distribution of the patients was 68 in thirties, 211 in fourties, 260 in fifties, 75 in sixties, 50 in seventies, 6 in eighties and 1 in nineties.Seven males (1.2%) of the glottic cancer and eight males of precancer (seven hyperkeratosis and one leukoplakia) were found among the 611 patients. In these laryngeal cancers, six cases were T1a of early stage and one was T3 in the classification by Intenational Union Against Cancer (UICC).Other 596 patients distributed to 296 chronic laryngitis, 60 acute laryngitis, 66 laryngeal polyp, 41 Rienkes edema, 55 laryngeal nodule and others.We achieved our purpose by early detection of six glottic cancers in this mass examination, and look foward to the examination same as ours in other prefectures.