The Kresge Hearing Research Institute-3 (KHRI-3) antibody binds to a guinea pig inner ear supporting cell antigen (IESCA) and causes hearing loss. To gain insight into the mechanism of antibody-induced hearing loss, we used antibody immunoaffinity purification to isolate the IESCA, which was then sequenced by mass spectroscopy, revealing 10 guinea pig peptides identical to sequences in human choline transporter-like protein 2 (CTL2). Full-length CTL2 cDNA sequenced from guinea pig inner ear has 85.9% identity with the human cDNA. Consistent with its expression on the surface of supporting cells in the inner ear, CTL2 contains 10 predicted membrane-spanning regions with multiple N-glycosylation sites. The 68 and 72 kDa molecular forms of inner ear CTL2 are distinguished by sialic acid modification of the carbohydrate. The KHRI-3 antibody binds to an N-linked carbohydrate on CTL2 and presumably damages the organ of Corti by blocking the transporter function of this molecule. CTL2 mRNA and protein are abundantly expressed in human inner ear. Sera from patients with autoimmune hearing loss bind to guinea pig inner ear with the same pattern as CTL2 antibodies. Thus, CTL2 is a possible target of autoimmune hearing loss in humans.
Based on our data and a review of the literature, definitive RT provides cure rates that are as good as those after surgery, and is associated with a lower rate of severe complications. Patients with lateralized tumors may be safely treated with ipsilateral field arrangements. Our limited experience with intensity modulated radiotherapy suggests that it is as efficacious as conventional RT.
Only a small percentage of thyroid nodules require surgical management. Diagnosis and treatment selection require a risk stratification by history, physical examination, and ancillary tests. Nodules causing airway compression or those at high risk for carcinoma should prompt evaluation for surgical treatment. In nodules larger than 1 cm, fine-needle aspiration biopsy is central to the evaluation as it is accurate, low risk, and cost effective. Subcentimeter nodules, often found incidentally on imaging obtained for another purpose, can usually be evaluated by ultrasonography. Other laboratory and imaging evaluations have specific and more limited roles. An algorithm for the evaluation of the thyroid nodule is presented.
This review discusses the role of postoperative radiotherapy (RT) for patients with squamous cell carcinoma of the head and neck. Patients with unfavorable pathologic features have a high-risk of local-regional recurrence and a decreased likelihood of survival after surgery alone. Postoperative RT reduces the risk of local-regional failure and probably improves survival. Patients who are at high risk for recurrence may benefit from more aggressive altered fractionation schedules to decrease the overall time from surgery to the completion of RT. Adjuvant cisplatin-based chemotherapy also appears to improve the probability of cure in high-risk patients.
To determine whether antibodies to supporting cells are associated with response to corticosteroids in patients with autoimmune sensorineural hearing loss. Design: Prospective analysis of antibody to inner-ear antigens. Setting: Collaborating otology practices in Pennsylvania, Michigan, and Indiana. Patients: Sixty-three patients with rapidly progressive unilateral or bilateral sensorineural hearing loss of unknown cause suggestive of autoimmune sensorineural hearing loss. Interventions: Pretreatment audiometry, serum analysis by Western blot (WB) and immunofluorescence (IF) tests, corticosteroid therapy, and follow-up audiometry. Main Outcome Measures: Antibody reactivity and audiogram changes were analyzed for association with response to treatment. Results: More than half of the patients (37/63) had antibodies to both a 68-to 72-kDa protein and to innerear supporting cells, 16 patients had positive results on one assay only, and 10 had negative results on both. Twenty-eight patients improved and 35 did not. The WB findings did not correlate with response. Of the WBpositive patients, 49% (21/43) improved, as did 35% (7/ 20) of the WB-negative patients (P=.30). In contrast, 53% (25/47) of IF-positive patients improved, compared with only 19% (3/16) in the IF-negative group (P = .02). Of those who improved, 89% (25/28) were IF positive. Conclusions: Antibody to an inner-ear supporting cell antigen was significantly associated with hearing improvement after corticosteroid therapy (relative rate, 2.8). Patients with IF-positive serum are nearly 3 times more likely to experience improved hearing with corticosteroid treatment than those who are IF negative. Antibodies to inner-ear supporting cell antigen may have value in diagnosis and treatment of patients with autoimmune sensorineural hearing loss.
To show clinical benefit in the main outcome measures by the use of a standardized protocol for identification, characterization, and treatment of alcohol withdrawal syndrome (AWS) in postoperative patients with head and neck cancer.
Rates of local-regional control, survival, and complications support the use of postoperative radiation in selected patients. Tumor control and survival will hopefully improve further with the addition of chemotherapy to postoperative radiation.
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