Mining immune epitopes in the inner ear.

Etiologies for many inner ear disorders, including autoimmune inner ear disease, sudden sensorineural hearing loss, and Meniere's disease, remain unknown. Indirect evidence suggests an immune-mediated process involving an allergic or autoimmune mechanism. We examined whether known immunogenic proteins share sequence similarity with inner ear proteins, which may lead to cross-reactivity and detrimental immune activation. Comprehensive bioinformatic analyses of primary sequences of intact and mutated proteins associated with human hearing loss and all proteins known to be expressed in the human inner ear were compared with all immune epitopes in the Immune Epitope Database. The exact match and basic local alignment search tool computational algorithms identified 3036 and 106 unique epitope matches, respectively, the majority of which were infectious epitopes. If validated in future clinical trials, these candidate immune epitopes in the inner ear would be potential novel targets for diagnosis and treatment of some inner ear disorders and the resulting hearing loss.

A comparison of two methods for preventing cross-contamination when using flexible fiberoptic endoscopes in an otolaryngology clinic: disposable sterile sheaths versus immersion in germicidal liquid.

OBJECTIVES/HYPOTHESIS: To assess the efficacy of using a sterile sheath to prevent cross-contamination when using a fiberoptic nasopharnygolaryngoscope (FNPL) in an otolaryngology clinic. STUDY DESIGN: Prospective controlled trial. METHODS: All FNPLs were disinfected according to applicable current guidelines recommended by the US Center for Disease Control. Swabs were taken from multiple sites on 100 FNPLs for cultures to detect the presence of bacteria, viruses, or both. Each FNPL was then assigned to either the sheath alone (experimental) or germicidal immersion (control) group. After using an FNPL in a patient, swabs were again taken so that a comparison could be made in microbes on the scopes. Throughout the study, the steps in the disinfection process taken by medical assistants as they worked with the FNPLs were observed and recorded. RESULTS: Microbial counts on insertion shafts of FNLPs for the sheath and immersion groups were similar, with 1/50 versus 0/50, respectively. Time spent using the sheath method averaged 89 seconds, whereas immersion in the germicidal liquid took 14 minutes. No breaches in adherence to applicable protocols were observed. CONCLUSIONS: Using an individually packaged disposable sterile sheath on a FNLP prevents microbes from adhering to the shaft of the scope, thus providing a reasonably safe method of avoiding the transmission of infection from one patient to the next patient when using an FNLP successively in multiple patients in an otolaryngology clinic.

Anatomy-based algorithms for detecting oral cancer using reflectance and fluorescence spectroscopy.

OBJECTIVES: We used reflectance and fluorescence spectroscopy to noninvasively and quantitatively distinguish benign from dysplastic/malignant oral lesions. We designed diagnostic algorithms to account for differences in the spectral properties among anatomic sites (gingiva, buccal mucosa, etc). METHODS: In vivo reflectance and fluorescence spectra were collected from 71 patients with oral lesions. The tissue was then biopsied and the specimen evaluated by histopathology. Quantitative parameters related to tissue morphology and biochemistry were extracted from the spectra. Diagnostic algorithms specific for combinations of sites with similar spectral properties were developed. RESULTS: Discrimination of benign from dysplastic/malignant lesions was most successful when algorithms were designed for individual sites (area under the receiver operator characteristic curve [ROC-AUC],0.75 for the lateral surface of the tongue) and was least accurate when all sites were combined (ROC-AUC, 0.60). The combination of sites with similar spectral properties (floor of mouth and lateral surface of the tongue) yielded an ROC-AUC of 0.71. CONCLUSIONS: Accurate spectroscopic detection of oral disease must account for spectral variations among anatomic sites. Anatomy-based algorithms for single sites or combinations of sites demonstrated good diagnostic performance in distinguishing benign lesions from dysplastic/malignant lesions and consistently performed better than algorithms developed for all sites combined.

A controlled safety study of diindolylmethane in the immature rat model.

OBJECTIVES/HYPOTHESIS: Diindolylmethane (DIM), a natural product from cruciferous vegetables, has been shown to be a dietary component that has inhibitory effects on some tumors (e.g., laryngeal papilloma). However, current evidence to support its safety is based on adult humans or mature animals. There is little to show on its safety in children. This study is designed to assess safety in the young rat model. STUDY DESIGN: Prospective controlled animal study. METHODS: Forty rats were separated into four treatment groups of 10 rats each, based on the amount of study drug they received in their daily food: 1) immature rats fed a low dose of DIM, (0.6 mg/kg/day); 2) immature rats fed a high dose of DIM (6.0 mg/kg/day); 3) immature rats fed no DIM (control); and 4) adult rats fed a high dose of DIM (6.0 mg/kg/day). At the conclusion of the study we collected blood to compare serum chemistries and vitamin D levels, and harvested organs to observe for any gross or histological changes among the groups. Statistical methods involved one-way analysis of variance and pairwise comparisons with Tukey multiple comparison adjustment. RESULTS: Although our numbers do not allow for statistical significance, there was no appreciable difference in rat weights among the immature groups, nor was there appreciable difference in serum chemistries, or gross or histological examination of liver, kidney, and bone. CONCLUSIONS: Diindolylmethane seems to have no adverse affects on the rat even when given in doses 3x what we propose to be therapeutic. This adds evidence to the safety of this drug in the pediatric population as a treatment option for recurrent respiratory papilloma.

Disorders of swallowing: palliative care.

This article defines palliative care for swallowing disorders as treatment for severe and chronic dysphagia or intractable aspiration when the recovery of normal swallowing is not anticipated and attempts to restore normal swallowing have been unsuccessful. Palliative treatment for dysphagia is not only for the dying patient because patients with difficulty swallowing can live for a long time. Palliative care for dysphagia is aimed at maximizing swallowing function, maintaining pulmonary health, and supporting healthy nutrition despite the impaired ability to swallow. When despite all attempts at intervention a patient becomes totally unable to swallow, the goal of therapy changes toward finding ways to provide adequate nutrition for the patient.

Palliative treatment of dysphonia and dysarthria.

The focus of this article is the palliative treatment of a variety of dysphonic conditions. Symptomatic relief of hoarseness can be achieved by voice therapy, augmentative alternative communication modalities, and surgery. The causes of dysphonia addressed herein include amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, stroke, head and neck cancers requiring glossectomy or laryngectomy, unilateral vocal fold paralysis, and presbyphonia. Palliative treatment of dysphonia and voice disorders provides symptomatic relief but not a cure of the underlying disease state. For these patients there are a number of palliative interventions that can greatly improve their quality of life.

Living with head and neck cancer and coping with dying when treatments fail.

Palliative care in patients who have head and neck cancer is a complex topic that requires a multifaceted approach. The head and neck surgeon has an important duty to fulfill in managing and following the wishes of the incurable cancer patient and is obligated to direct them to the appropriate services in this challenging time.

Quantitative spectroscopic imaging for non-invasive early cancer detection.

We report a fully quantitative spectroscopy imaging instrument for wide area detection of early cancer (dysplasia). This instrument provides quantitative maps of tissue biochemistry and morphology, making it a potentially powerful surveillance tool for objective early cancer detection. We describe the design, construction, calibration, and first clinical application of this new system. We demonstrate its accuracy using physical tissue models. We validate its diagnostic ability on a resected colon adenoma, and demonstrate feasibility of in vivo imaging in the oral cavity.

Retrospective evaluation of a method to predict fresh-frozen plasma dosage in anticoagulated patients.

In the United States, fresh-frozen plasma (FFP) is commonly used for urgent reversal of warfarin; however, dosage recommendations are difficult to find. If validated, a proposed method that uses a nonlinear relationship between international normalized ratio (INR) and clotting factor activity (CFa) would be useful. This study retrospectively evaluated a proposed equation with adult medical inpatients who received FFP for warfarin reversal. For each patient the equation was used to predict the dose of FFP required to achieve the observed change in INR, which was then compared to the actual dose. The equation was considered successful if the predicted dose was within +/-20% of the actual dose. Subgroup analyses included subjects who received concomitant vitamin K; subjects with supratherapeutic INRs (>3); and subjects with significantly elevated INRs (>5). Of the 209 patients screened, 91 met criteria for inclusion in the study. Use of the equation to calculate the predicted dose of FFP was successful in 11 patients (12.1%) with use of actual body weight for prediction and in 23 patients (25.3%) with use of ideal body weight (P = 0.02). The equation performed similarly in all subgroups analyzed. The mean predicted FFP dose was significantly greater than the actual dose in all patients when actual body weight was used (925.2 mL vs. 620.6 mL; P < 0.001). Least-squares regression modeling of repeat INR (converted to CFa) produced a model that accounted for 57% of the variance in repeat INR. The value predicted from the model was closer to the actual CFa than was the value predicted from the published equation in every comparison, but it was statistically different only when actual body weight was used. This study revealed that a published equation for calculation of FFP dose to reverse oral anticoagulation resulted in doses that were significantly higher than the actual dose. Use of ideal body weight improved accuracy but was still not successful for the majority of patients. Until trials are able to prospectively demonstrate the accuracy of a dose-prediction model for FFP, dosing will remain largely empiric.

Model-based spectroscopic analysis of the oral cavity: impact of anatomy.

In order to evaluate the impact of anatomy on the spectral properties of oral tissue, we used reflectance and fluorescence spectroscopy to characterize nine different anatomic sites. All spectra were collected in vivo from healthy oral mucosa. We analyzed 710 spectra collected from the oral cavity of 79 healthy volunteers. From the spectra, we extracted spectral parameters related to the morphological and biochemical properties of the tissue. The parameter distributions for the nine sites were compared, and we also related the parameters to the physical properties of the tissue site. k-Means cluster analysis was performed to identify sites or groups of sites that showed similar or distinct spectral properties. For the majority of the spectral parameters, certain sites or groups of sites exhibited distinct parameter distributions. Sites that are normally keratinized, most notably the hard palate and gingiva, were distinct from nonkeratinized sites for a number of parameters and frequently clustered together. The considerable degree of spectral contrast (differences in the spectral properties) between anatomic sites was also demonstrated by successfully discriminating between several pairs of sites using only two spectral parameters. We tested whether the 95% confidence interval for the distribution for each parameter, extracted from a subset of the tissue data could correctly characterize a second set of validation data. Excellent classification accuracy was demonstrated. Our results reveal that intrinsic differences in the anatomy of the oral cavity produce significant spectral contrasts between various sites, as reflected in the extracted spectral parameters. This work provides an important foundation for guiding the development of spectroscopic-based diagnostic algorithms for oral cancer.