Quality of life impact of external beam radiotherapy for advanced thyroid carcinoma.

BACKGROUND: External beam radiotherapy (XRT) has an established role in the management of recurrent or advanced well-differentiated thyroid carcinoma (WDTC). The goal of this study was to investigate the impact of this additional intervention on the quality of life (QOL) compared with total thyroidectomy (TT), with or without adjuvant radioactive iodine (RAI). METHODS: A cross-sectional analysis using validated QOL instruments was performed. Patients receiving XRT between 1992 and 2008 for WDTC were identified and offered study participation. The Quality of Life Radiation Therapy Instrument and the Head and Neck Companion Module were administered retrospectively (N=13). For a comparison, patients previously treated with TT (N=11) alone as well as TT with postoperative RAI (N=11) for WDTC were also evaluated. RESULTS: Thirty-four patients were included in the analysis. The XRT group reported significant decreases in chewing, swallowing, and appetite, and significant increase in pain, compared with both the RAI group and the TT group. Significant differences were reported for questions with regard to peace of mind, feeling discouraged, saliva, taste, ability to eat regular food, and concerns for the appearance of the neck in both RAI and XRT groups compared with TT patients. Subscale analysis of head and neck specific questions demonstrated significant overall differences for both RAI and XRT groups compared with thyroidectomy alone, with no differences observed between RAI and XRT groups in a direct comparison. CONCLUSIONS: RAI therapy results in a measurable decrease in head and neck specific QOL measures compared with TT alone. The addition of XRT results in additional measurable morbidity secondary to pain and dysphagia.

Identification and characterization of pannexin expression in the mammalian cochlea.

The gap junction in vertebrates is encoded by the connexin gene family. Recently, a new gene family termed pannexin (Panx) has been identified in vertebrates and found to encode gap junctional proteins as well. To date, three pannexin isoforms (Panx1, 2, and 3) have been cloned from mouse and human genomes. In this study, expression of pannexins in the mouse and rat cochlea was investigated. Polymerase chain reaction and Western blot analysis showed that all three pannexin isoforms were expressed in the cochlea. Immunofluorescent staining showed that Panx1 expression was extensive. In the organ of Corti, Panx1 labeling was found in supporting cells, including pillar cells, Hensen cells, Claudius cells, and Boettcher cells. Both surface plaque-like punctate labeling and diffuse-cytoplasmic labeling were visible. However, the labeling was weak and rare in Deiters cells. No labeling was found in the hair cells. Intense labeling for Panx1 was also observed in the interdental cells in the spiral limbus, the inner and outer sulcus cells, and the type II fibrocytes in the spiral prominence and central region in the cochlear lateral wall. In addition, Panx1 labeling was detectable in Reissner's membrane and strial blood vessel cells. Panx2 labeling was restricted to the basal cells in the stria vascularis and was also detectable in the spiral ganglion neurons. However, no overlapping labeling for Panx1 and Panx2 was observed. Finally, Panx3 labeling was exclusively observed in the cochlear bone. Thus, Panx1, 2, and 3 are abundantly expressed in the mammalian cochlea and demonstrate distinct cellular distributions. Like connexins, they may play an important role in hearing.

Voltage-dependent currents in isolated vestibular afferent calyx terminals.

Na(+) currents were studied by whole cell patch clamp of chalice-shaped afferent terminals attached to type I hair cells isolated from the gerbil semicircular canal and utricle. Outward K(+) currents were blocked with intracellular Cs(+) or with extracellularly applied 20 microM linopirdine and 2.5 mM 4-aminopyridine (4-AP). With K(+) currents blocked, inward currents activated and inactivated rapidly, had a maximum mean peak amplitude of 0.92 +/- 0.60 (SD) nA (n = 24), and activated positive to -60 mV from holding potentials of -70 mV and more negative. The transient inward currents were blocked almost completely by 100 nM TTX, confirming their identity as Na(+) currents. Half-inactivation of Na(+) currents occurred at -82.6 +/- 0.9 mV, with a slope factor of 9.2 +/- 0.8 (n = 7) at room temperature. In current clamp, large overshooting action potential-like events were observed only after prior hyperpolarizing current injections. However, spontaneous currents consistent with quantal release from the hair cell were observed at holding potentials close to the zero-current potential. This is the first report of ionic conductances in calyx terminals postsynaptic to type I hair cells in the mammalian vestibular system.