Uptake and retention of gentamicin by cells in the guinea pig inner ear after a single peritoneal injection or local application on the round window were investigated using immunocytochemistry to localize the drug. The cells that accumulated the drug under the two conditions were the same, but staining for the drug was more intense and was often accompanied by widespread cochlear degeneration following local application. Soon after drug administration by either route, there was diffuse staining for the drug throughout all tissue within the labyrinth, including bone. At later times when distinct cell staining became evident, virtually all cell types were found to be positive, with several cell types staining more darkly for the drug than hair cells, indicating that hair cells were not the most avid in accumulating gentamicin. The infracuticular portion of auditory and vestibular hair cells as well as type III fibrocytes of the spiral ligament were positively stained in almost all cases and these sites were found to be positive for as long as six months post administration. In animals with loss of the organ of Corti, there was unusually intense staining for gentamicin in root cells of the spiral ligament, in marginal cells of the stria vascularis, and in cells of the spiral limbus. Dark staining of surviving cells in cases with overt tissue destruction suggests that variability in the extent of damage caused by the drug was determined more by the degree of its local uptake than by differences in animals' capacities to metabolize the drug systemically. The present results show that gentamicin may damage or destroy all cochlear cells following a single round window application. The findings broaden the scope of our knowledge of cochlear gentamicin uptake and damage and have implications for treatment of patients with vestibular disorders by infusion of aminoglycosides into the middle ear, as well as implications for prospects of rehabilitating patients that have been deafened by aminoglycosides.

We retrospectively analyzed the clinical records of 137 patients who were treated at our clinic for acute low-tone sensorineural hearing loss of unknown cause over a period of 8 years. The analyses of the clinical records indicated the following clinical characteristics: female preponderance; peak incidence during the fourth decade of life; frequent accompanying tinnitus, sensation of ear fullness, and/ or autophony; suspicion of bilateral involvement; and association with autonomic imbalance. The hearing in most of the patients completely recovered, but some selected patients experienced fluctuating hearing loss or progression to Meniere's disease. Our results suggest that a subgroup of patients with severe initial hearing loss should be carefully followed up, although it is difficult to predict the outcome of this disorder.

Fifty patients (14 men and 36 women ranging in age from 16 to 66 years) with acute low-tone sensorineural hearing loss (ALHL) were retrospectively analyzed in this study. The glycerol test and the orthostatic test were performed. On the glycerol test, 43.8% of 16 ears of the 14 men and 33.3% of 39 ears of the 36 women with ALHL had a positive result. On the orthostatic test, 42.9% of the 14 men and 52.7% of the 36 women with ALHL had a positive result. In addition, 28.6% of the 14 men and 33.3% of the 36 women had hypotension with a systolic blood pressure of 100 mm Hg or less. Our results suggest that endolymphatic hydrops as shown by the glycerol test and an underlying autonomic imbalance and/or insufficient blood circulation as shown by the orthostatic test may be important factors in the causation of ALHL.

Calcium ions are known to play critical roles in a variety of cochlear functions. The distributions of a number of calcium binding proteins that regulate calcium ion levels within the cochlea have previously been described. In this report we extend and refine previous reports of the distribution of immunostaining for calmodulin, calbindin, and calretinin and show for the first time the distribution for peptide 19. There were longitudinal and radial gradients of immunostaining for peptide 19 within outer hair cells that appeared to match previously described gradients of efferent innervation of these cells. Gradients of immunostaining for calbindin within outer hair cells were in the opposite directions, which suggests that levels of this protein are correlated with afferent innervation density and perhaps the abundance of subsurface cisternae. No gradients were seen in the distributions of cells stained for calmodulin and calretinin, which included sensory cells and supporting cells respectively. All ganglion cells were stained for calmodulin but the other proteins appeared to be present in limited ganglion cell subpopulations. In addition to staining of sensorineural elements, antisera to all compounds but peptide 19 showed immunostaining of cells within the lateral wall and the spiral limbus. The results suggest that the proteins under study are involved in a wide variety of calcium-regulated functions within the cochlea. Knowledge of the unique distribution of each of the compounds should facilitate further studies of their roles in cochlear function.

The long-term therapeutic efficacy of isosorbide, an oral hyperosmotic diuretic, was clinically evaluated in 30 patients (14 males and 16 females) who were followed up in our clinic for more than 2 years. The patients ranged in age from 14 to 73 years, with a mean age of 49.2 years. Isosorbide was given orally, continuously or intermittently, for 27-297 weeks, depending on each patient’s condition. The efficacy of the drug was determined according to the evaluation criteria of the American Academy of Ophthalmology and Otolaryngology (AAOO) and the American Academy of Otolaryngology, Head and Neck Surgery (AAO-HNS) for Ménière’s disease. Definitive episodes were successfully controlled in 15 of the 20 patients (75%) who received isosorbide continuously according to both the AAOO and the AAO-HNS criteria. Of the 10 patients who were given the drug intermittently, definitive episodes were successfully controlled in 6 patients (60%) according to the AAOO and in 7 patients (70%) according to the AAO-HNS criteria. During the treatment periods, hearing improved in 6 patients (20%), and tinnitus subjectively lessened in 15 patients (50%). Although some patients complained of abdominal discomfort, the side effects of this drug were minimal. Among the patients who responded well to the treatment, the doses of isosorbide could be tapered to a daily dose of 30 ml, less than one half of the usual daily dose of this drug. The results suggest that most patients should be asked to continue this medical treatment for at least several months before a decision can be made regarding whether the medical response is good or poor. We believe that the long-term use of isosorbide is often efficacious in stabilizing the disabling symptoms of Ménière’s disease.