Transforming growth factor alpha with insulin stimulates cell proliferation in vivo in adult rat vestibular sensory epithelium.

Hair cells, the sensory receptors of the mammalian inner ear, have long been thought to be produced only during embryogenesis, and postnatal hair cell loss is considered to be irreversible and is associated with permanent hearing and balance deficits. Little is known about the factors that regulate hair cell genesis and differentiation. The mitogenic effects of insulin and transforming growth factor alpha (TGFalpha) were assayed in vivo in normal and drug-damaged rat inner ear. Tritiated thymidine and autoradiographic techniques were used to identify cells synthesizing DNA. Simultaneous infusion of TGFalpha and insulin directly into the inner ear of adult rats stimulated DNA synthesis in the vestibular sensory receptor epithelium. New supporting cells and putative new hair cells were produced. Infusion of insulin alone or TGFalpha alone failed to stimulate significant DNA synthesis. These results suggest that exogenous growth factors may have utility for therapeutic treatment of hearing and balance disorders in vivo.

Cochlear pathology induced by aminoglycoside ototoxicity during postnatal maturation in cats.

Cochlear pathology resulting from neonatal administration of the aminoglycoside antibiotic, neomycin sulfate, was studied in young kittens at 15-24 days postnatal. Hearing thresholds showed severe to profound hearing loss in all but one animal. Scanning electron microscopy demonstrated that initial hair cell degeneration occurred in the extreme base (hook region) of the cochlea and sequentially progressed to the basal, middle, then the apical coil of the cochlea. The first row of outer hair cells degenerated first, followed by row 2, then row 3; the last cells to degenerate in a given region were the inner hair cells. This pattern of hair cell degeneration is similar to that seen in adults with neomycin ototoxicity. In contrast, the spiral ganglion exhibited a different pattern of degeneration with initial cell loss occurring in the middle of the cochlea, about 40-60% from the base (approximately 2.8-8 kHz). Thus, neuronal degeneration apparently is not secondary to sensory cell loss, but rather comprises an independent process in these neonatal animals. Taken together, the findings suggest that the spiral ganglion cell loss in the middle cochlear turn results from increased aminoglycoside sensitivity associated with an earlier initial onset of function in these neurons as compared to other cochlear regions.

Impact of neck dissection on quality of life.

OBJECTIVES: For decades, the gold standard for treatment of cervical metastasis was radical neck dissection (RND). Current oncologic philosophy allows for treatment of appropriately staged neck disease with modified radical neck dissection (MRND) or selective neck dissection (SND). The purposes of this study were to determine the impact of various forms of neck dissection on patients' quality of life (QOL) and to evaluate the responsiveness of the University of Washington (UW) QOL shoulder domain. STUDY DESIGN: Prospective accumulation of QOL data from patients treated for head and neck cancer at UW. METHODS: Eighty-four patients were identified from the UW QOL registry who had undergone neck dissection and had completed pretreatment and posttreatment QOL questionnaires at 6 and 12 months. RESULTS: Compared with pretreatment scores, the MRND and RND groups reported worse shoulder function at 6 and 12 months (P<.0005). The MRND group reported greater shoulder disability at 6 months compared with the SND group (P = .002), but by 12 months, there was no difference between the two groups. Shoulder function for the RND group was worse than the SND group at 6 and 12 months (P = .004). There was a trend toward decreased pain after treatment in the SND and MRND groups. There were no significant differences in subjective appearance, activity, recreation, chewing, swallowing, or speech in the three groups after treatment. CONCLUSIONS: Consistent with findings of published functional studies, this study confirmed that the three forms of neck dissection affect patients' QOL differently. This study demonstrates that the UW QOL shoulder domain is a responsive instrument in assessing the effect of neck dissection on shoulder function.

Quality of life in head and neck cancer.

Because treatments for patients with cancer of the head and neck can have major impact on physical, social, and psychological function, the collection of quality of life (QOL) data in this group of patients is critical for our specialty. The University of Washington Quality of Life data have been collected and analyzed on three subsets of cancer patients. Information learned from these patients is summarized and strategies for future projects are outlined.

Quality of life in patients with head and neck cancer: lessons learned from 549 prospectively evaluated patients.

OBJECTIVES: To summarize our quality-of-life (QOL) research findings for patients with head and neck cancer, to suggest areas for future productive QOL research, and to discuss how to undertake QOL studies in a cost-effective manner. DESIGN: Review of previously published analyses of advanced larynx cancer, advanced oropharynx cancer, and neck-dissection cases and current data from the complete set of patients. PATIENTS: From January 1, 1993, through December 31, 1998, data on 549 patients were entered in our head and neck database. Of these patients, 364 met additional criteria for histologic findings (squamous cell carcinoma) and the restriction of their cancer to 4 major anatomical sites (oral, oropharynx, hypopharynx, or larynx). Of these, 339 patients were more than 1 year beyond initial treatment. Complete baseline TNM staging and QOL data were obtained for 260 of these patients, of whom 210 presented with an untreated first primary tumor (index cases) to the University of Washington, Seattle. INTERVENTION: Pretreatment QOL was assessed with an interviewer-supervised self-administered questionnaire. Subsequent self-administered tests were completed at 3, 6, 12, 24, and 36 months. Other data collected on each patient included cancer site, stage, treatment, histologic findings, type of surgical reconstruction, and current disease and vital status. RESULTS/CONCLUSIONS: It is difficult to achieve "statistically significant" results in a single-institution setting. The "composite" QOL score may not be a sufficiently sensitive tool. Analysis of separate domains may be more effective.

Transforming growth factor-alpha with insulin induces proliferation in rat utricular extrasensory epithelia.

Hair cell loss in the human inner ear leads to sensorineural hearing loss and vestibular dysfunction. Recent studies suggest that exogenous addition of growth factors, for example, transforming growth factor-alpha with insulin, may stimulate the production of new supporting cells and hair cells in the mature mammalian vestibular sensory epithelium. Before any growth factor can be seriously considered for the treatment of clinical problems related to hair cell loss, its effects on the extrasensory epithelia must also be fully explored. The aim of this study was to determine whether transforming growth factor-alpha and insulin stimulate cell proliferation in rodent vestibular extrasensory epithelia. The cell proliferation marker, tritiated thymidine, was infused along with transforming growth factor-alpha, insulin, or transforming growth factor-alpha plus insulin into the inner ears of adult rats via osmotic pumps. Effects of the test agents were assessed on normal and drug-damaged utricles. Drug damage was produced by delivering gentamicin directly into the inner ear before the infusion of test agent. Animals were killed 4 or 10 days after pump placement. Utricles were sectioned, processed for autoradiography, and examined for labeled cells within the extrasensory epithelia. In normal animals, transforming growth factor-alpha plus insulin stimulated DNA synthesis in all regions of the extrasensory epithelia, suggesting that these agents are mitogenic for these tissues.