K. Ohashi

Ototoxicity of the Anticancer Drug Cisplatin:An Experimental Study

Cisplatin was administered to guinea pigs. Hearing function was tested using ABR, and morphological studies were conducted by scanning and transmission electron microscopy. The following findings were made. (1) The susceptibility to cochlear damage by cisplatin was dose dependent. (2) At the same dose, damage was most severe in the lower turns, particularly in the second turn. This tallies with the high tone loss. (3) Mainly the outer hair cells are the site of the damage and the inner hair cells are rarely damaged. (4) The first row of the outer hair cells tend to be more severely damaged. (5) Variation of the stria vascularis was moderate compared with the damage to the organ of Corti. (6) A tendency of recovery was observed in ABR in some animals after they were given 2 mg/kg/day cisplatin intramuscularly consecutively for 8 days.

Application of Loop Diuretics for Treatment of Sensorineural Hearing Impairment

In a series of animal experiments on guinea pigs and rats, conducted in an attempt to find a better solution for the treatment of sensorineural hearing impairment and tinnitus-known as diseases almost impossible to heal-it was revealed electrophysiologically, biochemically and electronmicroscopically that loop diuretics, referred to as ototoxic drugs, cause an increased amount of the therapeutic preparation to transfer to the inner ear fluid. It is concluded, on the basis of the encouraging results of these experiments, that combined medication with metabolic activator, steroid hormone and loop diuretics is significantly more effective in improving the symptoms of patients with inner ear deafness and tinnitus.

T cell subsets in the tonsil in relation to age analyzed with monoclonal antibodies (anti-leu antibodies) and fluorescence activated cell sorter (FACS)

The ratio of the cells reacting to anti-leu 1, 3a and 4 antibodies is as low as that of T cells in the tonsil to those in the peripheral blood. The number of the tonsillar cells reacting to anti-leu 2a and 7 antibodies is still smaller. Fluorescence intensity of tonsillar lymphocytes reacting to leu (1, 2a, 3a, and 4) antibodies is lower than that of peripheral blood lymphocytes. Adult tonsillar lymphocytes have higher ratios of the cells reacting to anti-leu 1, 2a, 3a, 4 and 7 antibodies than child tonsillar lymphocytes and fluorescence intensity of the cells reacting to these anti-leu antibodies tended to be higher in adult tonsillar lymphocytes. These findings suggest less cytotoxic/suppressor T and NK/K function cells in the tonsil than in the peripheral blood. From these, it is conceivable that the tonsillar lymphocyte constitution becomes closer to that of peripheral blood as the child grows up. Further, immature T cells are present in the tonsil, though in a small number. This tendency is stronger in children than in adults.

Microvasculature of the Tympanic Membrane

In order to investigate the blood flow of the tympanic membrane (TM) in various conditions, the microvasculature of the TM was observed by scanning electron microscope, using casting methods. Differences in vascular patterns between pars tensa and pars flaccida were observed, suggesting that vascular distribution in TM is closely concerned with the arrangement of radial fibers in the intermediate fibrous layer. Once inflammation was induced, changes in blood vessels quickly took place and most remarkably at the central zone of TM. The TM which closed earlier was found to leak resin at the edge of the perforation. It is proposed that an active blood flow to the perforation edge is necessary for a smooth closing.

Ototoxic Effect of an Aminoglycoside Drug on an Immature Inner Ear

In order to investigate to what extent an immature inner ear is injured by external causes, the effect of Kanamycin on an immature cochlea was studied in mice by using scanning and transmission electron microscopes. Our results showed that immature cochleae are more highly susceptible to injury than mature cochleae, especially when the Nuels space and the Corti tunnel open. It is suggested that in humans, during the stage corresponding to the above period, that is, in about the third gestational month, the inner ear is highly susceptible to injury by external causes.

The Effect of Blood Pressure on Inner Ear Blood Flow

SummaryWe investigated the effects of blood pressure on the blood flow in the inner ear as compared with other organs in normotensive rats (NR), spontaneously hypertensive rats (SHR) and renal hypertensive rats (RHR). The cardiac output and the regional blood flow were measured by a radioactive microsphere technique in conscious rats. The haemodynamics of the inner ear and other organs and the effects of a converting-enzyme inhibitor (SA-446) on the regional blood flow were compared among NR, SHR, and RHR, the blood pressure being 107, 152, and 185 mm Hg, respectively. With the exception of the heart, the organ blood flow was lower in SHR than in NR in all organs, including the inner ear. It was also lower in RHR than in SHR. The blood pressure dropped after i.v. injection of SA-446, while the regional blood flow increased. The effect was strongest in RHR, followed by SHR and finally NR.