Faculty Bibliography

Varicocele is the most common correctible cause of male infertility and is present in 15% to 20% of the male population. Despite its prevalence, the pathophysiology of varicocele remains under investigation. One of the largest obstacles in studying varicocele is that it is almost exclusively found in humans. This has necessitated the creation of an animal model of varicocele. The most commonly used animal model involves the creation of a varicocele in a rodent by partially occluding the left renal vein. This model has provided a significant amount of data on varicocele, and a modification of this model utilizing microsurgery appears even more promising. Animal models have proven critical to investigating the pathophysiology of varicocele.

BACKGROUND: Our objectives were to evaluate factors raised in malpractice litigation in which plaintiffs alleged that physician negligence led to olfactory dysfunction. METHODS: We analyzed publically available federal and court records using Westlaw, a widely used computerized legal database. Pertinent jury verdicts and settlements were comprehensively examined for alleged causes of malpractice (including procedures for iatrogenic causes), defendant specialty, patient demographics, and other factors raised in legal proceedings. RESULTS: Of 25 malpractice proceedings meeting inclusion criteria, 60.0% were resolved for the defendant, 12.0% were settled, and 28.0% had jury-awarded damages. Median payments were significant ($300,000 and $412,500 for settlements and awards, respectively). Otolaryngologists were the most frequently named defendants (68.0%), with the majority of iatrogenic cases (55.0%) related to rhinologic procedures. Associated medical events accompanying anosmia included dysgeusia, cerebrospinal fluid leaks, and meningitis. Other alleged factors included requiring additional surgery (80.0%), unnecessary procedures (47.4% of iatrogenic procedural cases), untimely diagnosis leading to anosmia (44.0%), inadequate informed consent (35.0%), dysgeusia (56.0%), and psychological sequelae (24.0%). CONCLUSION: Olfactory dysfunction can adversely affect quality of life and thus is a potential area for malpractice litigation. This is particularly true for iatrogenic causes of anosmia, especially following rhinologic procedures. Settlements and damages awarded were considerable, making an understanding of factors detailed in this analysis of paramount importance for the practicing otolaryngologist. This analysis reinforces the importance of explicitly including anosmia in a comprehensive informed consent process for any rhinologic procedure.

Animals modulate their arousal state to ensure that their sensory responsiveness and locomotor activity match environmental demands. Neuropeptides can regulate arousal, but studies of their roles in vertebrates have been constrained by the vast array of neuropeptides and their pleiotropic effects. To overcome these limitations, we systematically dissected the neuropeptidergic modulation of arousal in larval zebrafish. We quantified spontaneous locomotor activity and responsiveness to sensory stimuli after genetically induced expression of seven evolutionarily conserved neuropeptides, including adenylate cyclase activating polypeptide 1b (adcyap1b), cocaine-related and amphetamine-related transcript (cart), cholecystokinin (cck), calcitonin gene-related peptide (cgrp), galanin, hypocretin, and nociceptin. Our study reveals that arousal behaviors are dissociable: neuropeptide expression uncoupled spontaneous activity from sensory responsiveness, and uncovered modality-specific effects upon sensory responsiveness. Principal components analysis and phenotypic clustering revealed both shared and divergent features of neuropeptidergic functions: hypocretin and cgrp stimulated spontaneous locomotor activity, whereas galanin and nociceptin attenuated these behaviors. In contrast, cart and adcyap1b enhanced sensory responsiveness yet had minimal impacts on spontaneous activity, and cck expression induced the opposite effects. Furthermore, hypocretin and nociceptin induced modality-specific differences in responsiveness to changes in illumination. Our study provides the first systematic and high-throughput analysis of neuropeptidergic modulation of arousal, demonstrates that arousal can be partitioned into independent behavioral components, and reveals novel and conserved functions of neuropeptides in regulating arousal.

BACKGROUND: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear. METHODS: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ. RESULTS: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation. CONCLUSIONS: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Manipulations of the sensory environment typically induce greater changes to the developing nervous system than they do in adulthood. The relevance of these neural changes can be evaluated by examining the age-dependent effects of sensory experience on quantitative measures of perception. Here, we measured frequency modulation (FM) detection thresholds in adult gerbils and investigated whether diminished auditory experience during development or in adulthood influenced perceptual performance. Bilateral conductive hearing loss (CHL) of approximately 30 dB was induced either at postnatal day 10 or after sexual maturation. All animals were then trained as adults to detect a 5 Hz FM embedded in a continuous 4 kHz tone. FM detection thresholds were defined as the minimum deviation from the carrier frequency that the animal could reliably detect. Normal-hearing animals displayed FM thresholds of 25 Hz. Inducing CHL, either in juvenile or adult animals, led to a deficit in FM detection. However, this deficit was greater for juvenile onset hearing loss (89 Hz) relative to adult onset hearing loss (64 Hz). The effects could not be attributed to sensation level, nor were they correlated with proxies for attention. The thresholds displayed by CHL animals were correlated with shallower psychometric function slopes, suggesting that hearing loss was associated with greater variance of the decision variable, consistent with increased internal noise. The results show that decreased auditory experience has a greater impact on perceptual skills when initiated at an early age and raises the possibility that altered development of CNS synapses may play a causative role.

Long (31.5 mm) electrode arrays are inserted deeper into the cochlea than the typical 1.25 turn insertion. With these electrode arrays, the apical electrodes are closer to (and possibly extend past) the end of the spiral ganglion. Using multi-dimensional scaling with patients implanted with a 31.5 mm electrode array, the perceptual space between electrodes was measured. The results suggest that deeper insertion increases the range of place pitches, but the perceptual differences between adjacent electrodes become smaller in the apex.

Measures of human mental development suggest that behavioral skills displayed during early life can predict an individual's subsequent cognitive performance. Support for this draws from longitudinal studies that reveal compelling within-subject correlations during childhood. If this idea applies across the life span, then correlations in performance should persist into adulthood. Here, we address this prediction in juvenile and adult gerbils by evaluating within-subject measures of auditory learning and perception. Animals were trained and tested as juveniles on either an amplitude modulation (AM) or a frequency modulation (FM) detection task. Measures of learning and perception obtained from juveniles were then compared to similar measures obtained when each subject was tested in adulthood on either the same task or the untrained task. For animals trained and tested on the AM detection task as juveniles and adults, there was no correlation between juvenile and adult learning metrics, or perceptual sensitivity. For animals trained and tested on FM detection as juveniles, we observed a significant relationship to their adult performance. Juveniles that performed the best on FM detection were the poorest at AM detection, and the best at FM detection, when tested as adults. Thus, across-age correlations for sensory and cognitive measures, obtained during development and in adulthood, depend heavily on the specific type of developmental experience and the outcome measure. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

The purpose of this study was to investigate the reliability of tongue and handgrip strength and endurance measurements in healthy adults using the Iowa Oral Performance Instrument. Fifty-one healthy participants (21 males, 30 females; age range = 19-57 years) were tested on four occasions 1 week apart to determine test-retest reliability. The primary outcome measures were isometric tongue and handgrip strength (best of three trials) and sustained isometric endurance. Small increases (changes in group mean) in both anterior (1.7 %) and posterior (2.5 %) tongue strength and handgrip strength (5 %) between weeks 1 and 2 were observed with no change in subsequent weeks, suggesting that there is only a small learning effect for these measurements. The within-subject variation (mean-typical error expressed as a coefficient of variation [CV]) indicated higher than desirable initial variation for anterior (CV 10.8 %) and posterior (CV 11.8 %) tongue strength and handgrip strength (CV 15.2 %) but this was reduced in weeks 2-4. Intraclass correlation coefficients (ICC) indicated acceptable and improved reliability for both anterior (ICC 0.77-0.90) and posterior (ICC 0.79-0.86) tongue strength and handgrip strength (ICC 0.69-0.91) after week 1. Additional exploratory analyses were conducted with a subset of data to determine whether two values within 5 kPa (tongue) or 15 kPa (handgrip) provide superior strength reliability. Neither tongue nor hand endurance measurements were sufficiently reliable. These findings suggest that tongue and handgrip strength values demonstrate acceptable reliability, especially if familiarization is provided. Further investigation is needed to reduce sources of variability in tongue endurance measurements.

Should one use an open or closed rhinoplasty approach? How appropriate is the endonasal approach in modern-day rhinoplasty? Should the tip lobule be divided or preserved? Are alloplastic implants inferior to autologous implants? Does release and reduction of the upper lateral cartilages from the nasal dorsal septum always require spreader graft placement to prevent mid one-third nasal pinching in reduction rhinoplasty? Over past 5 years, how have rhinoplasty techniques and approaches evolved?

OBJECT: The resection of glomus jugulare tumors can be challenging because of their inherent vascularity. Preoperative embolization has been advocated as a means of reducing operative times, blood loss, and surgical complications. However, the incidence of cranial neuropathy associated with the embolization of these tumors has not been established. The authors of this study describe their experience with cranial neuropathy following transarterial embolization of glomus jugulare tumors using ethylene vinyl alcohol (Onyx, eV3 Inc.). METHODS: The authors retrospectively reviewed all cases of glomus jugulare tumors that had been treated with preoperative embolization using Onyx at their institution in the period from 2006 to 2012. Patient demographics, clinical presentation, grade and amount of Onyx used, degree of angiographic devascularization, and procedural complications were recorded. RESULTS: Over a 6-year period, 11 patients with glomus jugulare tumors underwent preoperative embolization with Onyx. All embolization procedures were completed in one session. The overall mean percent of tumor devascularization was 90.7%. No evidence of nontarget embolization was seen on postembolization angiograms. There were 2 cases (18%) of permanent cranial neuropathy attributed to the embolization procedures (facial nerve paralysis and lower cranial nerve dysfunction). CONCLUSION: Embolizing glomus jugulare tumors with Onyx can produce a dramatic reduction in tumor vascularity. However, the intimate anatomical relationship and overlapping blood supply between these tumors and cranial nerves may contribute to a high incidence of cranial neuropathy following Onyx embolization.