Faculty Bibliography

The success of replicating adenoviruses for cancer therapy is limited by inefficient virus delivery and poor distribution within the tumor mass. Stromal matrix within the tumor may hinder the free cell-to-cell spread of the virus. In this study, in vitro cell culture experiments showed that collagen I blocked the passage of an adenoviral vector through a membrane. On the basis of reports of the effective collagen I-degrading activity of matrix metalloproteinase-8 (MMP-8), we constructed an adenovirus to express the MMP-8 transgene (AdMMP8). A549 cells infected in vitro with AdMMP8 did not show altered growth but were able to modify a fibrillar collagen substrate to allow viral diffusion. Further, AdMMP8 did not affect replication of the wild-type virus (Adwt300). Established human A549 lung cancer and BxPC-3 pancreatic cancer xenograft tumors that were injected with Adwt300 together with the non-replicating AdMMP8 virus showed significantly reduced growth compared with control tumors. Histochemical analysis showed reduced amounts of collagen within necrotic areas of MMP-8-injected tumors compared with controls. These results demonstrate that intra-tumoral expression of MMP-8 is a possible strategy for improving viral spread and improving the oncolytic activity of replicating adenovirus

OBJECTIVES: To transcutaneously deliver intense ultrasound (IUS) energy to target the facial superficial musculoaponeurotic system (SMAS), to produce discrete thermal injury zones (TIZs) in the SMAS, and to demonstrate the relative sparing of adjacent nontargeted layers superficial and deep to the SMAS layer. METHODS: In 6 unfixed human cadaveric specimens, the SMAS layer was visualized and targeted using the ultrasound imaging component of the IUS device. Using 2 IUS handpieces, 202 exposure lines were delivered bilaterally in multiple facial regions by varying combinations of power and exposure time (0.5-8.0 J). Tissue was then excised and examined grossly and histologically for evidence of thermal injury using nitroblue tetrazolium chloride viability stain. RESULTS: Reproducible TIZs were produced selectively in the SMAS at depths of up to 7.8 mm, and sparing of surrounding tissue including the epidermis. Higher energy settings and high-density exposure line pattern produced a greater degree of tissue shrinkage. CONCLUSIONS: In human cadaveric facial tissue, IUS can noninvasively target and selectively produce TIZs of reproducible location, size, and geometry in the SMAS layer. The ability to produce focused thermal collagen denaturation in the SMAS to induce shrinkage and tissue tightening has not been previously reported and has significant implications for aesthetic facial rejuvenation

OBJECTIVES: To establish discriminant validity of the endoscopic sinus surgery simulator (ES3) (Lockheed Martin, Akron, Ohio) between various health care provider experience levels and to define benchmarking criteria for skills assessment. DESIGN: Prospective multi-institutional comparison study. SETTING: University-based tertiary care institution. PARTICIPANTS: Ten expert otolaryngologists, 14 otolaryngology residents, and 10 medical students. INTERVENTIONS: Subjects completed the ES3's virtual reality curriculum (10 novice mode, 10 intermediate mode, and 3 advanced mode trials). Performance scores were recorded on each trial. Performance differences were analyzed using analysis of variance for repeated measures (experience level as between-subjects factor). MAIN OUTCOME MEASURES: Simulator performance scores, accuracy, time to completion, and hazard disruption. RESULTS: The novice mode accurately distinguished the 3 groups, particularly at the onset of training (mean scores: senior otolaryngologists, 66.0; residents, 42.7; students, 18.3; for the paired comparisons between groups 1 and 2 and groups 1 and 3, P = .04 and .03, respectively). Subjects were not distinguished beyond trial 5. The intermediate mode only discriminated students from other subjects (P = .008). The advanced mode did not show performance differences between groups. Scores on the novice mode predicted those on the intermediate mode, which predicted advanced mode scores (r = 0.687), but no relationship was found between novice and advanced scores. All groups performed equally well and with comparable consistency at the outset of training. Expert scores were used to define benchmark criteria of optimal performance. CONCLUSIONS: This study completes the construct validity assessment of the ES3 by demonstrating its discriminant capabilities. It establishes expert surgeon benchmark performance criteria and shows that the ES3 can train novice subjects to attain those. The refined analysis of trial performance scores could serve educational and skills assessment purposes. Current studies are evaluating the transfer of surgical skills acquired on the ES3 to the operating room (predictive validity)

Penetrating trauma to the face and upper zone III of the neck may present unique challenges when the parotid gland and associated neurovascular structures are involved. We report a case of massive hemorrhage from penetrating neck trauma that necessitated emergency parotidectomy for vascular exposure. Facial nerve repair was also necessary, underscoring the importance of this approach not only for successful vascular control but also for preservation of nearby vital structures. The management of penetrating trauma to the parotid region,and relevant anatomy, are discussed

Spectrally-encoded miniature endoscopy uses a single optical fiber and wavelength division multiplexing to obtain macroscopic images through miniature, flexible probes. In turn, it has the potential to enable two- and three-dimensional imaging within the body at locations that are currently difficult to access with conventional endoscopes. Here we present a novel detection scheme for spectrally-encoded endoscopy using spectral-domain interferometry. Compared to previous time-domain configurations, this new detection method results in greater than 1000-fold increase in sensitivity (77 dB), a 6-fold increase in imaging speed (30 volumes per second), and a 2-fold increase in depth range (2.8 mm). We demonstrate spectrally-encoded, spectral-domain detection by conducting video-rate, three-dimensional imaging in a variety of specimens, including the paws of a mouse embryo and excised human ear bones. Our results show that this new technology enables video rate spectrally-encoded endoscopy and will therefore be useful for a variety of minimally invasive medical applications

Receptive fields of sensory cortical neurons are plastic, changing in response to alterations of neural activity or sensory experience. In this way, cortical representations of the sensory environment can incorporate new information about the world, depending on the relevance or value of particular stimuli. Neuromodulation is required for cortical plasticity, but it is uncertain how subcortical neuromodulatory systems, such as the cholinergic nucleus basalis, interact with and refine cortical circuits. Here we determine the dynamics of synaptic receptive field plasticity in the adult primary auditory cortex (also known as AI) using in vivo whole-cell recording. Pairing sensory stimulation with nucleus basalis activation shifted the preferred stimuli of cortical neurons by inducing a rapid reduction of synaptic inhibition within seconds, which was followed by a large increase in excitation, both specific to the paired stimulus. Although nucleus basalis was stimulated only for a few minutes, reorganization of synaptic tuning curves progressed for hours thereafter: inhibition slowly increased in an activity-dependent manner to rebalance the persistent enhancement of excitation, leading to a retuned receptive field with new preference for the paired stimulus. This restricted period of disinhibition may be a fundamental mechanism for receptive field plasticity, and could serve as a memory trace for stimuli or episodes that have acquired new behavioural significance

The aim of this study was to validate the published University of California San Francisco (UCSF) Oral Cancer Pain Questionnaire. To test for validity of the questionnaire, 16 patients with oral cancer completed the 8-item questionnaire immediately before and after treatment (surgical resection) of their oral cancer. For all 8 questions, the difference between mean preoperative and mean postoperative responses were statistically significant (P < .05), confirming the validity of the questionnaire to measure oral cancer pain. Internal consistency of the questionnaire was evaluated by using Cronbach's alpha, which provides an estimate of reliability based on all correlations between the items (questions) of the instrument (questionnaire). In the oral cancer pain questionnaire, questions 1, 3, and 5 evaluate the intensity, sharpness, and throbbing nature of pain when the patient is not engaged in oral function (talking, eating, and drinking). Questions 2, 4, and 6 measure the intensity, sharpness, and throbbing nature of pain during oral function. Cronbach's alpha for questions 1, 3, and 5 is 0.87 and Cronbach's alpha for questions 2, 4, and 6 is 0.94; values greater than 0.7 indicate reliability. In this study, we have validated the UCSF Oral Cancer Pain Questionnaire as an effective tool in quantifying pain from oral cancer. PERSPECTIVE: The study validates an oral cancer pain questionnaire. The questionnaire can be used to reliably measure pain levels before and after surgical resection in patients with oral cancer

The analysis of saliva has been proposed as a potentially rapid, non-invasive method to monitor and diagnose patients with oral disease. In this study we measured salivary endothelin-1 (ET-1) levels in patients diagnosed with oral squamous cell carcinoma (SCC) prior to treatment. We demonstrate significantly elevated salivary ET-1 levels in the oral SCC group (4.37+/-1.35pg/ml), relative to the control group (1.16+/-0.29pg/ml). ET-1 and ET-1 mRNA were also measured in oral SCC tissue specimens and compared to normal oral epithelial controls. The concentration of ET-1 in the oral SCC specimens was 17.87+/-4.0pg/ml and in the normal epithelial controls the concentration of ET-1 was 5.43+/-2.5pg/ml. ET-1 mRNA was significantly overexpressed in 80% (8/10) of the oral SCC specimens. Our results demonstrate the potential utility of salivary analysis for ET-1 levels to monitor patients at risk for oral SCC