Kuan Cheng Chang

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.

An experimental study on the progressiveness of cochlear damage by aminoglycoside drug.

The administration of the aminoglycoside antibiotics often gives rise to sensori-neural hearing loss. in a study undertaken to explore the progression of hearing loss caused by these drugs, guinea pigs were administered with kanamycin, a representative member of this family of antibiotics, and subsequently were investigated for the presence or absence of hearing loss and its progressive-ness during and after the period of medication in terms of audiogenic brain stem response (BSR). Further, in an attempt to investigate the relationship between the function and morphology of a KM-damaged inner ear, light microscopic as well as scanning and transmission electron microscopic examinations were made of the cochleas excised from the treated animals. the results are summarized as follows(1) Four distinct wave forms, i.e., P1, P2, P3 and P4, were seen in BSR tracings from normal guinea pigs.(2) a comparative study was made of BSR amplitude as an index of hearing. in the group receiving KM in consecutive daily dos...

Inner ear damage induced by bacterial endotoxin.

ZusammenfassungWiederholte i.d. Injektion von E. Coli-Endotoxin führt zur Degeneration der inneren und äußeren Haarzellen, vor allem an der Basalwindung mit teilweisem Verschwinden der Nervenfasern in der Lamina spiralis ossea. In der Stria vascularis finden sich erweiterte Interzellularräume sowie das Auftreten von Lysosomen in den Endothelzellen der Kapillaren. Im vestibulären Labyrinth zeigen sich verschiedene Degenerationsgrade der Sinneszellen vom Typ I und II an den Cristae ampullares sowie an den Maculae mit teilweisem Fehlen dieser Zellen. An den dunklen Zellen finden sich Vakuolen und erweiterte Zwischenräume. Die Befunde legen die Vermutung nahe, daß auch die Shwartzman-Reaktion als Ursache für Störungen der Innenohrfunktion in Frage kommt.SummaryRepeated i.d. injection doses of endotoxin lipopolysaccharide of E. coli at certain time intervals were found to give rise to the following changes in the inner ear in mice:In the organ of Corti of the cochlea, there were noted degeneration and disappearance of the inner and outer hair cells of the lower turn, partly with a partial disappearance of nerve fibers in the osseous spiral lamina. Degenerative changes seen in the upper turn were of milder degree.The stria vascularis exhibited enlarged intercellular spaces, the appearance of lysosomes in the constituent cells, and degeneration thereof.Changes observed in the vestibular organ were varying degrees of degeneration of types I and II sensory cells of the crista ampullaris and macula as well as a partial disappearance of these cells.The dark cells were found to have undergone such changes as the formation of vacuoles of varying size and widened interspaces between infoldings, thus providing presumptive evidence of a change in the composition of the endolymph.These observations suggest the possibility that Shwartzman reaction might be another probable cause of inner ear deafness or equilibrium disturbances in actual clinical cases which are at present claimed to be of unknown etiology.

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.

Variation in Bacterial Count in Otorrhea from Cases of Chronic Otitis Media Depending Upon the Method of Antibiotic Administration

Patients with chronic otitis media (COM) were divided into two groups, one to be given Cephalexin (CEX) orally and the other to be given CEX ear drops locally. The counts of viable bacteria in otorrheal samples collected before and after CEX administration were determined. The incidence of decrease in the count of bacteria was higher in the group given ear drops than in the group given oral doses. The magnitude of decrease was greater in the former group. Various concentration of CEX representing the levels of the drug considered available at an otitis focus following oral administration were added to otorrheal preparations placed in biophotometer cells. After 24 hours of incubation, bacteria as undetected initially in the otorrhea were found in the biophotometer cells in 3 of 14 cases of COM.

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.

Respiratory Viruses and Mycoplasma Pneumoniae Infections at the Time of the Acute Exacerbation of Chronic Otitis Media

The present study was undertaken to ascertain whether or not patients with chronic otitis media are infected with viruses or Mycoplasma at the time of sudden increase in otorrhea. From 26 patients with acute exacerbation of chronic otitis media, sera were collected at the time of sudden increase in otorrhea and three to four weeks later. These paired sera were examined for antibody titer to respiratory viruses (21 species) and Mycoplasma pneumoniae. Of them, influenza B virus and RSV infections were demonstrated in four and two cases, respectively. Examinations showed no infection in 10 control cases without acute exacerbation. In 36 cases of acute exacerbation of chronic otitis media, attempts were made to isolate viruses and Mycoplasma pneumoniae from the pharynx and otorrhea. Consequently, influenza B virus was detected in pharyngeal mucous scrapings in two cases and RSV in one. The probability of respiratory virus infection leading to acute exacerbation of chronic otitis media appears to be lower than that provoking acute otitis media in children and infants. However, the present data suggest that the development of respiratory virus infection in patients with chronic otitis media may cause an increase in the otorrhea, eventually resulting in an acute exacerbation of inflammation.

Location of Intravenously Injected Kanamycin Sulfate in the Middle Ear Mucosa

Twelve guinea pigs were treated with intravenous kanamycin sulfate (KM) and sacrificed 2, 5, 10, and 30 min later to investigate its location in the middle ear mucosa, especially in the Eustachian tube (ET). Immunological examinations evidenced KM in the epithelial and subepithelial layers of the ET on each occasion of observation. But, it was never recognized in the tubal gland. These observations might indicate that clinically used drugs easily get to the ET except for the tubal gland which might have some barrier mechanism against foreign bodies.

Vertex Evoked Potential in Guinea Pigs

In the present study, the effects of exposure to high intensity noise arid ototoxic medication on hearing were investigated using the vertex provocative reaction, one of the objective hearing tests. Guinea pigs were exposed to high intensity pure tone, 2000 or 4000 Hz, 110-120 dBSPL, for 10 minutes or 1.5 hours. Nitromin and Furosemide were used for ototoxic medication. (1) Immediately after exposure to pure tone of high intensity, the threshold of reaction was elevated and the amplitude returned to a pre-exposure level later. (2) Intravenous injection of nitromin was followed by a similar increase in amplitude. A marked reduction in amplitude to a premedication level was observed 2 days after the administration of nitromin. (3) Following the administration of Furosemide there was a rapid decrease in amplitude with its subsequent gradual recovery. This phenomenon was considered to be due to changes in the stria vascularis. Changes in the function of hearing that occurred in an incipient stage of inner ear damage when no morphological changes were as yet demonstrable were thus studied in terms of EEG otological provocative reaction.