Identification of altered protein abundances in cholesteatoma matrix via mass spectrometry-based proteomic analysis.

BACKGROUND: Cholesteatoma are cyst-like structures lined with a matrix of differentiated squamous epithelium overlying connective tissue. Although epithelium normally exhibits self-limited growth, cholesteatoma matrix erodes mucosa and bone suggesting changes in matrix protein constituents that permit destructive behaviour. Differential proteomic studies can measure and compare the cholesteatoma proteome to normal tissues, revealing protein alterations that may propagate the destructive process. METHODS: Human cholesteatoma matrix, cholesteatoma-involved ossicles, and normal middle ear mucosa, post-auricular skin, and non-involved ossicles were harvested. These tissues were subjected to multiplex peptide labeling followed by liquid chromatography and tandem mass spectrometry analysis. Relative protein abundances were compared and evaluated for ontologic function and putative involvement in cholesteatoma. RESULTS: Our methodology detected 10 764 peptides constituting 1662 unique proteins at 95 % confidence or greater. Twenty-nine candidate proteins were identified in soft tissue analysis, with 29 additional proteins showing altered abundances in bone samples. Ontologic functions and known relevance to cholesteatoma are discussed, with several candidates highlighted for their roles in epithelial integrity, evasion of apoptosis, and immunologic function. CONCLUSION: This study produced an extensive cholesteatoma proteome and identified 58 proteins with altered abundances contributing to disease pathopathysiology. As well, potential biomarkers of residual disease were highlighted. Further investigation into these proteins may provide useful options for novel therapeutics or monitoring disease status.

Evidence-based practice: management of adult sensorineural hearing loss.

Sensorineural hearing loss is a complex disease state influenced by genetics, age, noise, and many other factors. This article reviews our current knowledge regarding the causes of sensorineural hearing loss and reviews the more challenging clinical presentations of sensorineural hearing loss. We have reviewed the latest medical literature in an attempt to provide an evidence-based strategy for the assessment and management of sudden sensorineural hearing loss, rapidly progressive sensorineural hearing loss, and asymmetric/unilateral sensorineural hearing loss.

Systematic review and meta-analysis of the risk factors for sudden sensorineural hearing loss in adults.

OBJECTIVES/HYPOTHESIS: To review the medical literature evidence of potential risk factors for sudden sensorineural hearing loss (SSNHL) in the adult general population. STUDY DESIGN: Systematic review of prospective and retrospective studies; meta-analysis of case-controlled studies. METHODS: Three researchers independently reviewed MEDLINE (January 1, 1950-November 30, 2010), Embase (January 1, 1980-November 30, 2010), and Evidence-Based Medicine Reviews databases in addition to conducting a manual reference search. Randomized controlled trials, prospective cohort studies, consecutive/nonconsecutive case series, and retrospective reviews in which a clear definition of SSNHL was stated were included in the study. Researchers individually extracted data regarding patient information and the presumed risk factors. Discrepancies were resolved by mutual consensus. RESULTS: Twenty-two articles met the inclusion criteria. Cardiovascular risk factors (smoking, increased alcohol consumption) appeared to be associated with a higher risk of developing SSNHL. A low level of serum folate may also be implicated as a risk factor. Factor V Leiden and MTHFR gene polymorphisms were found to occur more frequently in patients with SSNHL in several studies, suggesting these inherited prothrombophilic mutations could be independent risk factors of SSNHL. CONCLUSIONS: Acquired and inherited cardiovascular risk factors appeared to be associated with an increased risk of developing SSNHL.

Systematic review of the evidence for the etiology of adult sudden sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: To determine the evidence for different etiologies of sudden sensorineural hearing loss (SSNHL) identified by clinical diagnostic tests in the adult population. STUDY DESIGN: Systematic literature review. METHODS: Review of MEDLINE (1950-October 2009), EMBASE (1980-October 2009), and EBM Review databases in addition to manual reference search of identified papers. Randomized controlled trials, prospective cohort studies, and retrospective reviews of consecutive patients in which a clear definition of SSNHL was stated and data from consecutive patients were reported with respect to etiology of hearing loss. Three researchers independently extracted data regarding patient demographic information, diagnostic tests employed, and the identified presumed etiologies. Discrepancies were resolved by mutual consensus. RESULTS: : Twenty-three articles met the inclusion criteria. The first group of papers searched for different etiologies among patients with SSNHL. Multiple etiologies were identified, including viral infection, vascular impairment, autoimmune disease, inner ear pathology, and central nervous system anomalies. The diagnosis for the majority of patients remained idiopathic. The second group of papers evaluated SSNHL patients with specific diagnostic tests such as autoimmune markers, hemostatic parameters, and diagnostic imaging. CONCLUSIONS: The suspected etiologies for patients suffering sudden sensorineural hearing loss included idiopathic (71.0%), infectious disease (12.8%), otologic disease (4.7%), trauma (4.2%), vascular or hematologic (2.8%), neoplastic (2.3%), and other causes (2.2%). Establishment of a direct causal link between SSNHL and these etiologies remains elusive. Diagnostic imaging is a useful method for identification of temporal bone or intracranial pathology that can present with SSNHL as a primary symptom.

A systematic review of neonatal toxoplasmosis exposure and sensorineural hearing loss.

INTRODUCTION: The Joint Committee on Infant Hearing 2007 Position Statement includes in utero toxoplasmosis infection as a risk indicator for delayed-onset or progressive sensorineural hearing loss. It is recommended that children with congenital toxoplasmosis infection undergo audiologic monitoring to identify congenital and delayed-onset sensorineural hearing loss. OBJECTIVE: To determine the prevalence of sensorineural hearing loss and to develop evidence-based guidelines for audiologic monitoring of children born with congenital toxoplasmosis infection. DATA SOURCES: Systematic search of Medline, EMBASE and Cochrane databases and manual search of references. STUDY SELECTION: Longitudinal studies reporting an inception cohort identified at birth, with serologic confirmation of toxoplasmosis infection, and long-term serial audiometric evaluation. DATA EXTRACTION: Independent extraction of patient and audiometric data. DATA SYNTHESIS: Descriptive statistics. CONCLUSION: The five studies meeting our inclusion criteria report a prevalence of toxoplasmosis-associated hearing loss from 0% to 26%. Improved treatment regimens for toxoplasmosis may account for this range. Three treatment groups were identified and a subgroup analysis of the compiled data was performed. In children receiving limited or no treatment, the prevalence of toxoplasmosis-associated SNHL was found to be 28%. In children prescribed 12 months of antiparasitic treatment but in whom treatment was not confirmed to have started prior to 2.5 months of age and in whom compliance was not ensured, the prevalence of SNHL was 12%. In children treated with 12 months of antiparasitical therapy initiated prior to 2.5 months of age with serologically-confirmed compliance, the prevalence of SNHL was 0%. Only two longitudinal studies were identified and neither reported any cases of delayed-onset or progressive toxoplasmosis-associated SNHL. Children who have received a 12-month course of antiparasitical therapy initiated prior to 2.5 months with serologically-confirmed compliance should have repeat audiometric evaluation at 24-30 months of age. Children with congenital toxoplasmosis that had no treatment, partial treatment, delayed onset of treatment, or compliance issues should undergo annual audiologic monitoring until able to reliably self-report hearing loss.