Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss.

BACKGROUND: Chronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model. METHODS: We generated persisters (PCs) and inoculated them into the mouse middle ear cavity. We tracked infection with IVIS and detected PA using RT-PCR. We assessed cochlear damage and innate immunity by Immunohistochemistry. Finally, we evaluated cytokines with multiplex assay and quantitative real-time PCR. RESULTS: We observed outer hair cell (OHC) loss predominantly in the basal turn of the cochlear at 14 days after bacterial inoculation. Macrophages, not neutrophils are the major immune cells in the cochlea in CSOM displaying increased numbers and a distribution correlated with the observed cochlear injury. The progression of the morphological changes suggests a transition from monocytes into tissue macrophages following infection. We also show that PA do not enter the cochlea and live bacteria are required for cochlear injury. We characterized cytokine activity in the CSOM cochlea. CONCLUSIONS: Taken together, this data shows a critical role for macrophages in CSOM-mediated sensorineural hearing loss (SNHL).

Coronary bypass surgery for patients with chronic poor preoperative left ventricular function (EF<30%): 5-year follow-up.

BACKGROUND: Optimal therapy for patients with coronary artery disease and chronic poor left ventricular function, given the absence of randomized trials, is unclear. Although coronary surgery has been performed in such patients for 25 years, it is perceived as high risk and unproven long-term benefit, especially if thallium scanning fails to demonstrate large areas of viability. We report the results of coronary surgery in these patients. METHODS: Retrospective analysis by a standardized patient questionnaire, of 107 such consecutive patients offered coronary surgery. RESULTS: Mean follow-up was 3.3 years (range, 0.5-5.5); average patient age was 64.4+/-1 years. Preoperative thallium scans were performed solely on 31 patients with none or mild angina, of which 10 (32%) demonstrated large areas of viable myocardium. Perioperative mortality was 1.9%. On multivariate analysis, factors predictive of increased perioperative death were recent myocardial infarction (p<0.001) and nonelective surgery (p<0.001). Kaplan-Meier 5-year survival and freedom from major adverse cardiac events were 72.3 and 82.3%, respectively. In 21 patients, with preoperative nil-to-mild angina and nil-to-small areas of myocardial viability, thallium scanning failed to predict a successful outcome. CONCLUSION: Offering coronary surgery to these patients irrespective of thallium testing is safe and effective in the medium term. Early surgery is recommended.