Faculty Bibliography

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

OBJECTIVES: To determine the incidence of methicillin-resistant Staphylococcus aureus (MRSA)-positive surgical site infections after face-lift surgery and to discuss the screening, prevention, and treatment of such infections. METHODS: The patient charts of 780 patients who underwent a deep-plane rhytidectomy between 2001 and 2007 were reviewed for postoperative wound infections. Culture results and sensitivities were recorded. To our knowledge, this is the first study that documents MRSA-positive surgical site infections after face-lift surgery. RESULTS: Five of 780 patients (0.6%) who underwent face-lift surgery by the senior surgeon had postoperative surgical site infections. Four of the 5 patients had cultures that were positive for MRSA. Two of these patients (0.3%) required hospitalization and had collections that had to be opened or drained and developed wound breakdown. Both patients eventually responded to wound care along with intravenous and then oral antibiotic therapy. The other 2 MRSA-infected patients responded to oral antibiotic therapy and local wound care alone. The 2 complicated infections occurred on postoperative days 5 and 8. These 2 patients were the only ones among the 5 patients with positive cultures who had known recent contact with another physician or a hospital. All infections occurred in the year 2006, with 3 patients experiencing infection in the last 4 months of the year. Herein, we describe the incidence and sequelae of MRSA infections and colonization. The 2 major different subsets of MRSA are community-acquired MRSA and health care-associated MRSA. Surgical site infections that are positive for MRSA blur this division, which affects many aspects of the course of disease and treatment. We also discuss strategies for screening, preventing, and treating MRSA surgical site infections. CONCLUSIONS: Methicillin-resistant S aureus-positive surgical site infection is an increasingly problematic issue in all surgical fields. In the future, MRSA-positive infections will be more prevalent and will require well-developed screening, prevention, and treatment strategies

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

Oral squamous cell carcinoma (SCC) has an unpredictable capacity to metastasize to the neck, an event that dramatically worsens prognosis. Metastasis occurs even in earlier stages when no neck lymph node involvement is clinically detectable (N0). Management of the N0 neck, namely when and how to electively treat, has been debated extensively. This article presents the controversies surrounding management of the N0 neck, and the benefits and pitfalls of different approaches used in evaluation and treatment. As current methods of assessing the risk for occult metastasis are insufficiently accurate and prone to underestimation of actual risk, and because selective neck dissection (SND) is an effective treatment and has minimal long-term detriment to quality of life, the authors believe that all patients who have oral SCC, excluding lip SCC, should be prescribed elective treatment of the neck lymphatics. However, this opinion remains controversial. Because of the morbidity of radiation therapy and because treatment of the primary tumor is surgical, elective neck dissection is the preferred treatment. In deciding the extent of the neck dissection, several retrospective studies and one randomized clinical trial have shown SND of levels I through III to be highly efficacious

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