Chlorpromazine alters outer hair cell electromotility.

OBJECTIVE: Outer hair cells (OHCs) of the inner ear rapidly convert electrical gradients into mechanical force, enhancing cochlear sensitivity and frequency selectivity. We investigated the effect of chlorpromazine, an antipsychotic medication that alters membrane biomechanics, on OHC electromotility. STUDY DESIGN: Isolated guinea pig outer hair cells were perfused with chlorpromazine under whole-cell patch-pipette recording conditions. Electromotile responses were measured. RESULTS: A dramatic, reversible, dose-dependent depolarization of voltage at peak capacitance (V(pkCm)) was seen with chlorpromazine treatment. The gain of the electromotile response was maximal near V(pkCm) both before and after chlorpromazine application. Unlike the 3 other agents that alter electromotility (salicylate, lanthanides, membrane tension), chlorpromazine did not change peak capacitance (Cm(pk)), which varies directly with maximal electromotile gain. CONCLUSION: Chlorpromazine changes the membrane voltage at which OHCs exhibit maximal electromotile gain, without changing the magnitude of electromotile responses. SIGNIFICANCE: Chlorpromazine may diminish hearing thresholds or otoacoustic emissions in large doses.

Factors related to outcome of salvage therapy for isolated cervical recurrence of squamous cell carcinoma in the previously treated neck: a multi-institutional study.

OBJECTIVE: The goal was to identify factors associated with the outcome of salvage therapy for patients with isolated cervical recurrences of squamous cell carcinoma in the previously treated neck (ICR-PTN). STUDY DESIGN AND SETTINGS: A tumor registry search for ICR-PTN patients was performed at 7 participating institutions, and the charts were reviewed. Kaplan-Meier plots for survival and time until re-recurrence were used to evaluate the significance of associated variables. RESULTS: Median survival and time until re-recurrence were both 11 months. Survival was better in patients with the following characteristics: nonsurgical initial neck treatment, negative initial disease resection margins, no history of prior recurrence, ipsilateral location of the ICR-PTN relative to the primary, and use of surgical salvage. CONCLUSIONS: By pooling the experience of 7 US tertiary care medical centers, we have identified 5 factors that are associated with outcome of salvage therapy for ICR-PTN. SIGNIFICANCE: Consideration of these factors, as well as the reviewed literature, should facilitate patient selection for salvage protocols.

Use of plain radiography and computed tomography to identify fish bone foreign bodies.

INTRODUCTION: Fish bones are the most common aerodigestive foreign bodies in adults. Radiographic studies, often ordered for diagnosis, have questionable utility. METHODS: With a laryngoscope, bones from 10 fish species were placed in a variety of positions in a human head and neck cadaver specimen. Plain films and CT scans were obtained and evaluated by blinded readers. RESULTS: Plain radiography exhibited a sensitivity and specificity of 39% and 72%. Cooking did not grossly change radio-opacity. The species of fish affected visibility in soft tissue, without correlation to the characteristic optical density of each species. Bones placed orthogonal to the film in the vallecula were most readily identified. CT scanning correctly identified 9 of 10 bones. CONCLUSIONS: Plain radiography poorly visualizes fish bone foreign bodies in soft tissue; visibility varied with fish species, location, and orientation. CT is the test of choice to radiographically diagnose fish bone impactions.

Salicylate induced changes in outer hair cell lateral wall stiffness.

Micropipette aspiration was used to study the lateral wall stiffness of isolated guinea pig outer hair cells (OHCs) perfused with a sodium salicylate solution. Salicylate treatment significantly decreased lateral wall stiffness as measured by a stiffness parameter (S) compared to cells perfused with a standard bathing solution (S = 0.68 +/- 0.26 vs. S= 1.09 +/- 0.25, P < 0.05). The effect was reversible cells treated with salicylate and then with bathing solution exhibited a lateral wall stiffness similar to control cells (S = 1.10 +/- 0.40. P=0.94). Salicylate perfusion diminishes electromotile responses in isolated OHCs and physiologic doses of salicylate produce hearing loss and tinnitus in human subjects. The OHC lateral wall, the locus of electromotility, consists of three concentric layers: (1) an outermost plasma membrane, (2) a cytoskeletal network of actin and spectrin called the cortical lattice and (3) an innermost collection of flattened membranes called the subsurface cisternae (SSC). Ultrastructural studies have shown that salicylate treatment dilates and vesiculates the lateral wall subsurface cisternae (SSC) in guinea pig OHCs. In addition, salicylate causes an outward curvature of plasma membranes in human erythrocytes. The reversible, salicylate induced increase in lateral wall compliance may result from a direct action on the SSC and/or the plasma membrane.

Micropipette aspiration on the outer hair cell lateral wall.

The mechanical properties of the lateral wall of the guinea pig cochlear outer hair cell were studied using the micropipette aspiration technique. A fire-polished micropipette with an inner diameter of approximately 4 microm was brought into contact with the lateral wall and negative pressure was applied. The resulting deformation of the lateral wall was recorded on videotape and subjected to morphometric analysis. The relation between the length of the aspirated portion of the cell and aspiration pressure is characterized by the stiffness parameter, K(s) = 1.07 +/- 0.24 (SD) dyn/cm (n = 14). Values of K(s) do not correlate with the original cell length, which ranges from 29 to 74 microm. Theoretical analysis based on elastic shell theory applied to the experimental data yields an estimate of the effective elastic shear modulus, mu = 15.4 +/- 3.3 dyn/cm. These data were obtained at subcritical aspiration pressures, typically less than 10 cm H2O. After reaching a critical (vesiculation) pressure, the cytoplasmic membrane appeared to separate from the underlying structures, a vesicle with a length of 10-20 microm was formed, and the cytoplasmic membrane resealed. This vesiculation process was repeated until a cell-specific limit was reached and no more vesicles were formed. Over 20 vesicles were formed from the longest cells in the experiment.