Decreased intramuscular calcium hydroxyapatite implant resorption in a murine model of osteoporosis.

OBJECTIVE: Calcium hydroxyapatite (CaHA) is a common material for vocal fold injection augmentation. Durability is variable, and factors involved in implant longevity are not understood. Animal models of osteoporosis show decreased bone density and increased mineral liberation, suggesting CaHA retention may be altered in these conditions. STUDY DESIGN: Prospective murine investigation. METHODS: Fourteen skeletally mature, 10-month-old female Sprague-Dewley rats were treated by one of three interventions: oophorectomy, laparotomy without oophorectomy (sham), or monthly risedronate injection (90 µg/kg, subcutaneous). CaHA was implanted into the right lateral thigh muscle in all animals at the time of procedure or first risedronate injection. After 17 weeks, all rats were sacrificed, and the residual CaHA isolated from excised lateral thigh muscle through incubation in a 900 °C calcinator for 9 hours. RESULTS: Mean CaHA mass remaining in the oophorectomy group was 65.9 (standard deviation ± 16.1) mg, compared to 44.4 ± 10.0 mg CaHA in the risedronate group and 48.6 ± 7.5 mg in the sham group. One-way analysis of variance found a statistically significant difference between the oophorectomy and risedronate groups but not between the sham and other groups, F(2,11) = 4.404, P = 0.039. CONCLUSION: Persistent estrogen deficiency in a murine model of osteoporosis demonstrated decreased rate of CaHA resorption. This suggests that hormone alterations associated with osteoporosis may alter the longevity of CaHA implant resorption through an uncertain mechanism. LEVEL OF EVIDENCE: NA. Laryngoscope, 2576-2580, 2018.

Ultrasound backscatter microscopy for imaging of oral carcinoma.

OBJECTIVES: Ultrasound backscatter microscopy (UBM), or ultrasound biomicroscopy, is a noninvasive, label-free, and ionizing radiation-free technique allowing high-resolution 3-dimensional structural imaging. The goal of this study was to evaluate UBM for resolving anatomic features associated with squamous cell carcinoma of the oral cavity. METHODS: The study was conducted in a hamster buccal pouch model. A carcinogen was topically applied to cheeks of 14 golden Syrian hamsters. Six additional hamsters served as healthy controls. A high-frequency (41 MHz, 6-mm focal depth, lateral and axial resolutions of 65 and 37 µm, respectively) UBM system was used for scanning the oral cavity after 14 weeks of carcinogen application. Histologic analyses were conducted on scanned regions. RESULTS: The histologic structure of buccal tissue and microvasculature networks could be visualized from the UBM images. Epithelial and mucosal hypertrophy and neoplastic changes were identified in animals subjected to the carcinogen. In animals with invasive squamous cell carcinoma, lesion development and destruction of the structural integrity of tissue layers were noted. CONCLUSIONS: In this pilot study, UBM generated sufficient contrast for morphologic features associated with oral carcinoma compared to healthy tissue. This modality may present a practical technique for detection of oral neoplasms that is potentially translatable to humans.

Age-related hearing loss in rhesus monkeys is correlated with cochlear histopathologies.

Audiometric hearing deficits are a common symptom of age-related hearing loss (ARHL), as are specific histopathological changes in the cochlea; however, very little data have been collected in non-human primates. To examine this relationship further, we collected auditory brainstem responses (ABRs) from rhesus monkeys spanning in age from 10 to 35 years old, and examined four different morphological features of their cochleae. We found significant correlations between ABR thresholds and the loss of outer hair cells and spiral ganglion cells, but not with the loss of inner hair cells or a reduced thickness of the stria vascularis. The strongest correlation with ABR thresholds was the number of different pathologies present. These findings show that while aged rhesus monkeys experience audiometric hearing deficits similar to that seen in humans, they are not correlated with a single peripheral deficit, but instead with a number of different underlying cochlear histopathologies, indicating that similar histopathologies may exist in geriatric humans as well.

Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model.

OBJECTIVE: To investigate the benefit of using time-resolved, laser-induced fluorescence spectroscopy for diagnosing malignant and premalignant lesions of the oral cavity. DESIGN: The carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) was applied to 1 cheek pouch of 19 hamsters. The contralateral pouch and the cheek pouches of 3 hamsters without DMBA exposure served as controls. SETTING: University of California, Davis. PARTICIPANTS: Twenty-two golden/Syrian hamsters. INTERVENTION: A nitrogen pulse laser was used to induce tissue autofluorescence between the wavelengths of 360 and 650 nm. MAIN OUTCOME MEASURES: Spectral intensities and time-domain measurements were obtained and compared with the histopathologic findings at each corresponding site. RESULTS: Spectral intensities and lifetime values at 3 spectral bands (SBs; SB1 = 380 +/- 10 nm; SB2 = 460 +/- 10 nm, and SB3 = 635 +/- 10 nm) allowed for discrimination among healthy epithelium, dysplasia, carcinoma in situ, and invasive carcinoma. The lifetime values at SB2 were the most important when distinguishing the lesions using only time-resolved parameters. An algorithm combining spectral fluorescence parameters derived from both spectral and time-domain parameters (peak intensities, average fluorescence lifetimes, and the Laguerre coefficient [zero-order]) for healthy epithelium, dysplasia, carcinoma in situ, and invasive carcinoma provided the best diagnostic discrimination, with 100%, 100%, 69.2%, and 76.5% sensitivity and 100%, 92.2%, 97.1%, and 96.2% specificity, respectively. CONCLUSIONS: The addition of time-resolved fluorescence-derived parameters significantly improves the capability of fluorescence spectroscopy-based diagnostics in the hamster buccal pouch. This technique provides a potential noninvasive diagnostic instrument for head and neck cancer.

Difluoromethylornithine-induced reversible hearing loss across a wide frequency range.

OBJECTIVES: Alpha-difluoromethylornithine (DFMO) is an antineoplastic agent that causes reversible hearing loss (HL) by an unknown mechanism. Previous neonatal gerbil studies have identified a dosing regimen of 1 g/kg per day of DFMO given for 3 weeks that results in reversible HL on click-evoked auditory brainstem response (ABR). The objectives of this study are 1) to measure HL and recovery at several frequencies in neonatal gerbils after DFMO therapy at two different dosing regimens and 2) to identify any effects of DFMO on cochlear histology. STUDY DESIGN: Prospective, nonrandomized, experimental design with placebo controls. METHODS: ABR to tone pips at 2, 4, 8, 16, and 32 kHz were recorded on 62 21-day-old Mongolian gerbils after daily subcutaneous injections of DFMO (group A at 1 g/kg, group B at 750 mg/kg) or saline from day 3 to day 20 after birth. Thirty-seven animals were retested after a 3-week drug-free recovery period. Twenty-seven animals were killed for analysis of cochlear histology. RESULTS: Animals that were administered DFMO demonstrated higher ABR thresholds across all five frequencies, with mean threshold differences of 21 to 29 dB in group A and 11 to 17 dB in group B as compared with controls. Higher thresholds were demonstrated at higher frequencies. Fewer side effects were noted at the lower dose. After a 3-week drug-free recovery period, auditory thresholds returned to pretreatment levels. No significant cochlear structural abnormalities were identified under light microscopy. CONCLUSION: An 18-day regimen of 750 mg/kg per day of DFMO given subcutaneously in neonatal gerbils causes minimal side effects with broad-frequency HL that, after 3 weeks of recovery, is fully reversible.