The concentration of free cisplatin was followed in plasma, scala tympani perilymph and cerebrospinal fluid (CSF) after an intravenous injection (12.5 mg/kg) in guinea pigs. Liquid chromatography with postcolumn derivatization was used for quantitative determination of the drug. The distribution of cisplatin to CSF was fast; at 10 min after drug administration the concentration was 7 μg/ml and the CSF:plasma ratio was 0.37. Cisplatin seems to distribute more slowly to the perilymphatic compartment. The highest concentration measured was 4 μg/ml at 20 min after the injection, and the perilymph:plasma ratio was 0.40 at that time. The concentration-time curves generated for cisplatin in perilymph and CSF were similar. No accumulation in the perilymphatic compartment or CSF was observed.

The effect on the electrophysiological hearing thresholds and the endocochlear DC potential (EP) was studied in four groups of guinea pigs receiving different doses of cisplatin. By multiple low-dose intraperitoneal injections a permanent hearing loss was produced without a permanent decrease of the EP. On the other hand, when cisplatin was given as a single high-dose intravenous injection, there was an impairment of the electrophysiological hearing thresholds and EP, depending upon the level of cisplatin dose. It is concluded that cisplatin-induced hearing loss is not necessarily a sequela to a loss of EP.

The effect of the combined administration of cisplatin and furosemide on the electrophysiological hearing thresholds and endocochlear DC potential (EP) was studied in guinea pigs. A lack of interaction was found in animals given repeated intraperitoneal injections of a low dose of cisplatin with a pharmacological dose of furosemide. An ototoxic interaction occurred when a moderately high dose of cisplatin was administered intravenously at a time when the strial function was most affected by a very high dose of furosemide. The interaction was seen both as a decreased EP and a pronounced shift of auditory thresholds. It is concluded that the stria vascularis plays a role in the ototoxic mechanism of cisplatin.

Acoustic middle ear muscle reflexes (AMR) were examined in nonanesthetized rabbits using clinical oto-impedance devices to determine the feasibility of utilizing clinically available instruments in studies of laboratory animals, particularly with regard to parameters such as probe tone frequency and intensity. The Karolinska Sjukhuset clinical impedance instrument and the Madsen Electronics ZO174 standard clinical impedance meter were used. The results of this study show that reliable AMRs and tympanograms can be obtained from rabbits with both clinical instruments. Probe tone frequencies in the range of 800-1,200 Hz were most effective for eliciting tympanograms and the AMR in rabbits. The probe tone level was also found to be an important factor, with the most reliable sound pressure level being around 70 dB SPL, and below that of the reflex threshold. Both clinical instruments recorded AMR threshold elevations in animals with 7th-nerve and cochlear lesions. AMR decay was observed at 8 and 12 kHz, but no decay was seen in normal-hearing animals up to 4 kHz, suggesting that this frequency may be suitable for detecting and measuring pathological decay in the rabbit. The overall results suggest that standard oto-impedance instruments with a probe tone frequency of 1,000 Hz may be used effectively in experimental studies of several aspects of the AMR in laboratory animals, such as rabbits.

Neural activity of single eighth nerve fibers was recorded with glass microelectrodes in anesthetized normal-hearing rabbits. The units had a spontaneous rate ranging from 0 to approximately 120 spikes/s. In a large number of fibers this rate was below 2 spikes/s. The frequency tuning curves (FTCs) had a tip and a tail region for fibers with a high or medium characteristic frequency (CF). For low-frequency units the FTC was more symmetrically U-shaped. The tip threshold reached the behavioral threshold and units with thresholds of up to more than 60 dB above the mean behavioral threshold were found. There was a weak negative correlation between spontaneous rate and tip threshold. Frequency selectivity, Q10, was about 2 for units with CF below 2 kHz and about 5 for those with CF above 4 kHz. The peristimulus time (PST) histogram showed an initial peak, a plateau, and poststimulus inhibition. For the majority of fibers the dynamic range was 20–30 dB. Some fibers did not reach saturation within the stimulus intensity available. The tip-to-tail distance was 50 dB for high-frequency units at one octave below CF, a matter of potential interest for further studies of animals with inner ear lesions.

Ototoxicity is one of the unwanted side effects of cisplatin treatment. The first sign of hearing loss usually appears 3-4 days after the drug administration and occurs primarily in the higher frequencies. One hundred and eighty-six women treated with a moderate dose of cisplatin (50 mg/m2 every 4 weeks) for gynaecological cancer were studied. No significant loss of hearing was detected in the speech frequency range. Since the cisplatin concentration in the inner ear is highest after a single high dose injection, systemic audiometric monitoring is advisable during cisplatin therapy with single high dose regimen.

A modification of the conventional method of freeze-fracturing is described. By the use of polyvinyl-alcohol, a high viscous fluid, the organ of Corti is better stabilized in the specimen holder. This fluid also facilitates a clean fracture through the organ of Corti proper and in a high number of cases gives a large replica void of contaminating biological tissue and free of folds. Examples of results produced with this technique are demonstrated.

Tumour material, collected by fine-needle aspiration according to Franzén (4) has been fixed and embedded for study with the transmission electron microscope (TEM). Different kinds of tumours, mainly from the head and neck region as well as experimental animal material (liver and salivary gland tissue from guinea-pigs) have been studied. It is possible to get material of good quality by careful processing of the specimens and the paper contains a number of micrographs showing such specimens. There is every reason to regard the results presented as an indication that electron microscopy can be used for more detailed studies in connection with fine-needle biopsy. It should be tried especially in those cases where it is of interest to follow a tumour during radiotherapy or treatment with antibiotics or cytotoxic drugs.

Modern methods for structural analysis have during the last decades enriched our knowledge about the organ of Corti. Especially electron microscopy, but also phase contrast microscopy has been important in this development. During the last few years scanning electron microscopy has rapidly become the tool of choise for several of those problems encountered in a structural analysis of the normal and pathologically altered organ of Corti. In many ways, scanning electron microscopy forms a bridge between the light microscope and the ordinary electron microscope.This paper gives a survey of our present knowledge of the organ of Corti and of the acoustic nerve as seen by preparation, by light, and by electron microscopy and also by aid of the scanning electron microscopy. The two different populations of sensory cells in the organ of Corti, the outer and inner hair cells, have many similar features. Thus they are both provided with sensory hairs and have cytoplasmic organelles organized in a very similar way. Still the innervation of inner and outer hair cells is rather different. This difference is especially pronounced when looking at nerve endings of type 2, which are generally believed to be of efferent nature. But there is a difference not only between the efferent endings of inner and outer hair cells. Also different rows of outer hair cells and different coils have a different kind of innervation. The problem of how the sensory cells are innervated is discussed.A problem of great interest for the understanding of cochlear physiology is the fluid transport in the cochlea and the nutrition of the cells in the organ of Corti. A report is given on recept studies on particle transportation in the organ of Corti. A large part of these studies were made mainly by C. Angelborg in our laboratory [in press]. They give an interesting view on the great importance of the supporting structures in the organ of Corti and the routes of transportation of particles and presumably also fluids.The spiral ganglion was described in a book of Kellerhals, Engström and Ades [1968]. A short survey is given of these ganglion cells. This description includes a report on the two populations of ganglion cells and on the complex vascular arrangement in this region.