Faculty Bibliography

Congenital venous vascular malformations of the head and neck are low-flow, nonproliferative lesions that should be distinguished from hemangiomas. The characteristic history and clinical findings can establish the diagnosis. Direct percutaneous puncture and contrast injection at the time of treatment delineate the lesion and its drainage pattern. Treatment must be individualized according to lesion extent, patient tolerance and physician experience. Sclerotherapy with ethanol has proved to be a successful treatment modality for these lesions, as demonstrated in this study of 57 patients. Surgery is used for treatment of clinically significant residual disease. A multidisciplinary approach to evaluation and treatment is key to successful management.

OBJECTIVE: This study describes the relationship between health-related quality of life (HRQOL) and depression in patients following major surgery for head and neck cancer. DESIGN: Cross-sectional study using medical chart review, patient interview, and test administration. METHOD: Fifty patients were evaluated 6 months to 6 years following surgery using one global HRQOL measure (The Functional Assessment of Cancer Therapy-General [FACT-G]); three disease-specific measures of HRQOL (the HN module of the FACT [FACT-HNS], The University of Washington Quality of Life Scale [UWQOL], and The Performance Status Scale for Head and Neck Cancer); and one measure of depression (The Beck Depression Inventory [BDI]). RESULTS: The study population showed a high occurrence of depressive symptoms (22%). A negative correlation existed between the BDI and HRQOL as measured by the FACT-G (r = -0.49, P < .001) and the UWQOL (r = -0.44, P = .003). When somatic symptoms of depression were removed, the BDI remained correlated with HRQOL and was most highly correlated with the Emotional Well-Being (EWB) subscale of the FACT-G (r = -0.42, P = .003). There was no correlation between clinician judgments of EWB and any patient-rated measures of HRQOL or depression. CONCLUSIONS: Results demonstrate an inverse relationship between patient-reported HRQOL and depression. The lack of correlation between physician and patient ratings of HRQOL and EWB stresses the importance of obtaining patient ratings in addition to traditional clinician ratings when assessing outcomes. Finally, the multidimensional construction of the FACT with its specific subscales may make it a useful clinical tool for assessing patient status and augmenting patient interviews.

An in vitro model for oral cancer was used to examine the growth inhibitory effects of chemopreventive agents when used singly and in combination. The model consists of primary cultures of normal oral epithelial cells, newly established cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the spice turmeric were tested. Cells were treated singly and in combination and effects on growth determined in 5-day growth assays and by cell cycle analysis. Effective dose 50s and the combination index were calculated with the computerized Chou-Talalay method which is based on the median-effect principle. Agents were shown to differ in their inhibitory potency. EGCG was less effective with cell progression; the cancer cells were more resistant than normal or dysplastic cells. In contrast, curcumin was equally effective regardless of the cell type tested. Cell cycle analysis indicated that EGCG blocked cells in G1, whereas curcumin blocked cells in S/G2M. The combination of both agents showed synergistic interactions in growth inhibition and increased sigmoidicity (steepness) of the dose-effect curves, a response that was dose and cell type dependent. Combinations allowed for a dose reduction of 4.4-8.5-fold for EGCG and 2.2-2.8-fold for curcumin at ED50s as indicated by the dose reduction index (DRI). Even greater DRI values were observed above ED50 levels. Our results demonstrate that this model which includes normal, premalignant and malignant oral cells can be used to analyse the relative potential of various chemopreventive agents. Two such naturally-occurring agents, EGCG and curcumin, were noted to inhibit growth by different mechanisms, a factor which may account for their demonstrable interactive synergistic effect.

BACKGROUND: A complete in vitro multi-stage carcinogenesis model for oral cancer was developed to examine chemopreventive strategies. In the present study, the effects of EGCG [(-)-epigallocatechin-3-gallate], the major constituent of green tea, is being examined to understand mechanisms of action. METHODS: Effects of EGCG on the cell populations were examined with growth assays, cell cycle analysis, and western blots for retinoblastoma protein (pRB). RESULTS: In each cell type, EGCG inhibited growth, with a decrease in efficacy as cells progressed from normal to cancer. A G1 block was induced with an increase in the underphosphorylated form of pRB; EGCG-induced inhibition was not permanent, cells recovered, and no resistance developed. CONCLUSIONS: Our multistage carcinogenesis model for chemoprevention was effective in defining the chemopreventive value of EGCG. The observation that cancerous oral epithelium was less responsive than normal or dysplastic tissues has implication in the use of this agent, and the mechanisms responsible for this result remain to be defined.

OBJECTIVE: The objective of this study was to identify individual sources of noise and their contribution to the overall noise that influences valid measurement of otoacoustic emissions in neonates. The hypothesis was that careful selection of eliciting signals and signal processing parameters, unique analysis of measured results, and control of certain subject characteristics would allow isolation of these individual noise sources and determine their relative influence. DESIGN: Eliciting signal parameters were optimized and held constant to minimize equipment noise. Analysis of noise floors in relation to signal level was used to identify equipment-related noise associated with changes in signal parameters. Analysis of noise floor distributions was used to determine whether environmental noise entered the measurements via inadequate coupling of the probe to the ear. The acoustic characteristics of the middle ear were varied via subject selection to determine the influence of middle-ear characteristics on noise floor levels. RESULTS: The two sources of noise associated with the measurement equipment need not contribute to the noise floor for biologically relevant otoacoustic emissions measurements (eliciting signal levels between 30 and 75 dB SPL). Of the two pathways identified for environmental noise, the pathway resulting from an inadequate seal between the probe and the ear canal can be eliminated. One of the two sources of noise related to the subject, noise resulting from biologic activity unrelated to the ear can be minimized. However, the remaining factor, the status of the middle ear, has been shown to contribute as much as 6 dB to the overall noise floor. CONCLUSIONS: Careful selection of signal parameters and additional data analyses and procedural variables can isolate or control several sources of noise that influence distortion product otoacoustic emission measurements in neonates. Tight coupling between the probe unit and the external ear canal should be maintained for all measurements. Middle ear abnormalities can increase noise floors up to 6 dB.

Protein tyrosine phosphatases (PTPases) are important regulators of signal transduction systems, but the specificity of their action is largely unexplored. We have approached this problem by attempting to map the subsite preferences of these enzymes using combinatorial chemistry approaches. Protein-tyrosine peptidomimetics containing nonhydrolyzable phosphotyrosine analogues bind to PTPases with high affinity and act as competitive inhibitors of phosphatase activity. Human PTP-1B, a PTPase implicated to play an important role in the regulation of growth factor signal transduction pathways, was used to screen a synthetic combinatorial library containing malonyltyrosine as a phosphotyrosine mimic. Using two cross-validating combinatorial chemistry screening approaches, one using an iterative method and the other employing library affinity selection-mass spectrometric detection, peptides with high affinity for PTP-1B were identified and subsite preferences were detailed by quantitatively comparing residues of different character. Consistent with previous observations, acidic residues were preferred in subsites X-3 and X-2. In contrast, aromatic substitutions were clearly preferred at the X-1 subsite. This information supports the concept that this class of enzymes may have high substrate specificity as dictated by the sequence proximal to the phosphorylation site. The results are discussed with regards to the use of combinatorial techniques in order to elucidate the interplay between enzyme subsites.

In the treatment of acoustic neuroma, operative results have improved greatly during recent years, with high rates of functional cranial nerve preservation. Because of this, it has become more important to consider issues of patient satisfaction and quality of life (QOL) following treatment for these lesions. The authors have developed a novel questionnaire designed to measure QOL in patients with acoustic neuromas, and they administered it to 50 consecutive patients at least 6 months after acoustic neuroma surgery. Overall QOL was judged to be good but with definite minor difficulties, including some problems with hearing, facial nerve function, headache, tinnitus, dizziness, activity level, enjoyment of life, and emotional well-being. No significant differences were found between age groups and different operative approaches, and only minor differences were found in relation to tumor size. Patients with intracanalicular tumors fared no better than those with cerebellopontine angle tumors. Analysis of the data suggests an overall good outcome from acoustic neuroma surgery; however, when discussing the possible effects on postoperative QOL, even the potential minor problems should not be minimized, especially in patients undergoing operation for small or intracanalicular tumors.