Faculty Bibliography

OBJECTIVE: To determine the efficacy of pantoprazole therapy for daytime somnolence, psychomotor vigilance, and quality of life in patients with mild-moderate obstructive sleep disordered breathing (OSDB) and gastroesophageal reflux disease (GERD). STUDY DESIGN: Randomized, double-blind, placebo-controlled crossover trial. METHODS: Sixty patients with daytime sleepiness, mild-moderate OSDB and GERD were randomly assigned a 2-week treatment with pantoprazole 40 mg or placebo followed by a 2-week washout period and crossover respectively to 2-week treatment with placebo or pantoprazole. Outcomes included Epworth Sleepiness Score (ESS), sleep-related quality-of-life (FOSQ), and reaction time. RESULTS: With pantoprazole, patients reported statistically significantly greater improvement of overall reflux symptoms (P = 0.0003) and in ESS (P = 0.04). A significant improvement was noted in FOSQ for both treatments with a trend toward greater improvement with pantoprazole (P = 0.058). No improvement in reaction times was observed. CONCLUSION: Patients with coexistent GERD and OSDB noted significant improvement in daytime sleepiness after treatment with pantoprazole over placebo likely related to a reduction in nocturnal reflux-related arousals

In previous works, the authors showed that using robot-assisted steerable electrode array insertions can significantly reduce the insertion forces compared to non-steerable electrode arrays. In addition to steering the electrode array, it is possible to change its angle of approach with respect to the scala tympani. This paper focuses on determining the relevance of changing the angle of approach of the electrode array by comparing steerable electrode array insertions using a two Degrees-of-Freedom (DoF) robot versus a four DoF robot. Optimal insertion path planning strategies are presented for both two and four DoF insertions. Simulation results and experiments show that the four DoF insertions can improve over two DoF insertions. Moreover, changing the angle of approach can further reduce the insertion forces. The simulation results also provide the workspace requirements for designing a custom parallel robot for robot-assisted cochlear implant surgery

Spike timing-dependent synaptic plasticity (STDP) plays an important role in neural development and information processing in the brain; however, the mechanism by which spike timing information is encoded into STDP remains unclear. Here, we show that a novel allosteric kinetics of NMDA receptors (NMDARs) is required for STDP. We developed a detailed biophysical model of STDP and found that the model required spike timing-dependent distinct suppression of NMDARs by Ca(2+)-calmodulin. This led us to predict an allosteric kinetics of NMDARs: a slow and rapid suppression of NMDARs by Ca(2+)-calmodulin with prespiking --> postspiking and postspiking --> prespiking, respectively. We found that the allosteric kinetics, but not the conventional kinetics, is consistent with specific features of amplitudes and peak time of NMDAR-mediated EPSPs in experiments. We found that the allosteric kinetics of NMDARs was also valid for synaptic plasticity induced by more complex spike trains in layer II/III of visual cortex. We extracted an essential synaptic learning rule by reduction of the allosteric STDP model and found that spike timing-dependent bidirectional role of postspiking in synaptic modification, which depends on the allosteric kinetics, is the essential principle in STDP. Thus, we propose a simple hypothesis of the allosteric kinetics of NMDARs that can coherently explain critical features of spike timing-dependent NMDAR-mediated EPSPs and synaptic plasticity

OBJECTIVE: To describe changes in disease-specific and global quality of life (QOL) for children with recurrent or chronic tonsillitis at 6 months and 1 year after tonsillectomy using two validated instruments, the Tonsil and Adenoid Health Status Instrument (TAHSI) and the Child Health Questionaire-PF28 (CHQ-PF28). STUDY DESIGN AND SETTING: A multicenter, prospective observational outcomes study. RESULTS: Ninety-two children, mean age (SD) 10.6 (3.4) years, enrolled with follow-up available for 58 children at 6 months and 38 children at 1 year. The children showed significant improvements in all subscales of the TAHSI including airway and breathing, infection, health care utilization, cost of care, eating and swallowing (all P < 0.001), and behavior (P = 0.01). Significant improvements were also found on several subscales of the CHQ-PF28, such as general health perceptions, physical functioning, parental impact, and family activities (all P < 0.001). CONCLUSION/SIGNIFICANCE: This uncontrolled study provides prospective evidence of improved disease-specific and global QOL in children after tonsillectomy

We have shown previously that auditory experience regulates the maturation of excitatory synapses in the auditory cortex (ACx). In this study, we used electron microscopic immunocytochemistry to determine whether the heightened excitability of the ACx following neonatal sensorineural hearing loss (SNHL) also involves pre- or postsynaptic alterations of GABAergic synapses. SNHL was induced in gerbils just prior to the onset of hearing (postnatal day 10). At P17, the gamma-aminobutyri acid type A (GABA(A)) receptor's beta2/3-subunit (GABA(A)beta2/3) clusters residing at plasma membranes in layers 2/3 of ACx was reduced significantly in size (P < 0.05) and number (P < 0.005), whereas the overall number of immunoreactive puncta (intracellular + plasmalemmal) remained unchanged. The reduction of GABA(A)beta2/3 was observed along perikaryal plasma membranes of excitatory neurons but not of GABAergic interneurons. This cell-specific change can contribute to the enhanced excitability of SNHL ACx. Presynaptically, GABAergic axon terminals were significantly larger but less numerous and contained 47% greater density of glutamic acid decarboxylase immunoreactivity (P < 0.05). This suggests that GABA synthesis may be upregulated by a retrograde signal arising from lowered levels of postsynaptic GABA(A)R. Thus, both, the pre- and postsynaptic sides of inhibitory synapses that form upon pyramidal neurons of the ACx are regulated by neonatal auditory experience

Inhibitory neurotransmission is a critical determinant of neuronal network gain and dynamic range, suggesting that network properties are shaped by activity during development. A previous study demonstrated that sensorineural hearing loss (SNHL) in gerbils leads to smaller inhibitory potentials in L2/3 pyramidal neurons in the thalamorecipient auditory cortex, ACx. Here, we explored the mechanisms that account for proper maturation of gamma-amino butyric acid (GABA)ergic transmission. SNHL was induced at postnatal day (P) 10, and whole-cell voltage-clamp recordings were obtained from layer 2/3 pyramidal neurons in thalamocortical slices at P16-19. SNHL led to an increase in the frequency of GABAzine-sensitive (antagonist) spontaneous (s) and miniature (m) inhibitory postsynaptic currents (IPSCs), accompanied by diminished amplitudes and longer durations. Consistent with this, the amplitudes of minimum-evoked IPSCs were also reduced while their durations were longer. The alpha1- and beta2/3 subunit-specific agonists zolpidem and loreclezole increased control but not SNHL sIPSC durations. To test whether SNHL affected the maturation of GABAergic transmission, sIPSCs were recorded at P10. These sIPSCs resembled the long SNHL sIPSCs. Furthermore, zolpidem and loreclezole were ineffective in increasing their durations. Together, these data strongly suggest that the presynaptic release properties and expression of key postsynaptic GABA(A) receptor subunits are coregulated by hearing

PURPOSE: Head and neck neoplasms requiring surgical resection of the mandible can have negative consequences on patient quality of life. For patients with segmental resections, the vascularized fibular free flap and nonvascularized iliac crest are frequently used. The fibula has surpassed the iliac crest in popularity due to the success associated with a vascularized graft; however, there still remain significant advantages with the nonvascularized graft. There has not been a study comparing the quality of life associated with these two methods of mandibular reconstruction. We carried out the following study to compare quality of life of both grafts in an attempt to help guide therapeutic decisions. PATIENTS AND METHODS: Twenty-nine patients at the University of California, San Francisco undergoing mandibular resection with subsequent reconstruction with either a vascularized fibular free flap or nonvascularized iliac crest bone graft were identified. Patient quality of life was assessed with a modified version of the University of Washington Quality of Life Questionnaire, version 4. RESULTS: Eighteen patients responded (10 reconstructed previously with a fibula, 8 with iliac crest reconstructions). Patients with an iliac crest bone graft had significantly better chewing and swallowing scores (P = .04, P = .049 respectively). There was also a trend for better taste (P = .067). When patients with a history of radiation therapy were excluded, differences in chewing and swallowing were not significant (P = .26 and P = .31 respectively), whereas taste was (P = .038). CONCLUSIONS: These findings suggest that reconstruction with the iliac crest had benefits in improved function (chewing, swallowing, and taste) rather than esthetics, donor site morbidity, or psychologic discomfort as was anticipated. However, prior radiation, a relatively frequent therapy in this patient population, presents an important confounding factor. Radiation therapy is difficult to control for without limiting an already scarce patient pool, and bears with it significant morbidity that likely influenced these findings. Further study is warranted to confirm the results and further distinguish the 2 groups

OBJECTIVES: To provide comprehensive temporal trend analysis of 5-year relative survival rates of laryngeal cancer using the Surveillance, Epidemiology, and End Results database; and to expand on prior reports by including inclusion of laryngeal tumor location, stage, age at diagnosis, treatment strategy, and histologic grade. DESIGN: Retrospective cohort analysis using the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. The Surveillance, Epidemiology, and End Results data were used to design 5 cohorts of patients with laryngeal cancer: 1977-1978, 1983-1984, 1989-1990, 1995-1996, and 2001-2002. Five-year survival rates were analyzed according to tumor site, stage, and grade; age at diagnosis; and treatment strategy. The joinpoint regression model was used to assess survival trends and their statistical significance. RESULTS: Among patients with supraglottic cancer, 5-year relative survival rates for distant disease worsened over time while rates for local and regional disease did not change (P = .01 and P > .05, respectively). For localized glottic cancer, survival remained stable from 1977-1978 to 2001-2002. However, patients with regional and distant glottic cancer demonstrated a significant decrease in survival in the past 3 decades (P < .001). This trend was independent of treatment strategy. Finally, the proportion of well-differentiated tumors in patients with regional laryngeal cancer decreased over time (P < .001 for supraglottic and P = .007 for glottic). CONCLUSIONS: A decreasing 5-year survival trend was found among patients with glottic cancer who had regional disease and in all patients with distant disease. Histopathologic trends not previously reported in those with laryngeal cancer seem to parallel those seen in other tobacco-related cancers. These trends may reflect the effect of birth cohorts and implicate the relationship between carcinogenic exposure and host factors, rather than the influence of treatment