Round window application of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced ototoxicity.

HYPOTHESIS: In this study we tested the effect of local administration of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 on cisplatin ototoxicity in guinea pigs to the round window membrane. BACKGROUND: Cisplatin is an important antineoplastic agent in the therapy of many malignancies. Its clinical utility is limited by severe side effects, including ototoxicity. Recent studies have shown protection against cisplatin ototoxicity in animal experiments by the systemic administration of D-methionine and sodium thiosulfate. Growth factors such as brain-derived neurotrophic factor and fibroblast growth factor-2 also have shown otoprotective effects in in vitro studies. METHODS: Osmotic pumps (Alzet) were implanted unilaterally in 30 guinea pigs. Five groups of six animals received either D-methionine, sodium thiosulfate, fibroblast growth factor-2, brain-derived neurotrophic factor, or saline 0.9%. Cisplatin was administered intraperitoneally for 5 consecutive days. Distortion product otoacoustic emissions were recorded every day. The animals were killed on day 6, and their cochleae were removed and analyzed by transmission electron microscopy. RESULTS: Compared with control animals, guinea pigs treated with D-methionine showed better otoacoustic emissions on days 3 and 4 (Mann-Whitney test, p < 0.05). The differences were not evident on days 5 and 6. Sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 showed no significant protective effect. CONCLUSION: Local application to the round window membrane can be used as an effective treatment in the prevention of cisplatin toxicity. Local application may avoid systemic side effects and reduce the antineoplastic effects of cisplatin.

Prognostic implications of hemoglobin levels before and after surgery as well as before and after radiochemotherapy for head and neck tumors.

Several studies have shown that tumor cells may develop resistance to radiotherapy, proliferating under hypoxic conditions. Following surgery, patients may develop low hemoglobin levels, which may cause low oxygen conditions. This retrospective analysis was undertaken to determine the impact of low hemoglobin levels in patients with head and neck tumors treated with combined-modality therapy (surgery and postoperative radiochemotherapy). We studied 120 patients with mostly advanced head and neck tumors (88% stage III/IV) who had undergone macroscopically complete resections of their primary tumors and lymph node metastases. At 20-277 days after surgery (median: 51.3 days), these patients received postoperative chemoradiotherapy (56.7 Gy of radiation over 28-49 days and cisplatin 6 mg/m(2) body surface area on radiation treatment days with a cumulative dose of 96 mg/m(2)). Normal hemoglobin levels were considered to be 12 g/dl for females and 13 g/dl for males. Decreased hemoglobin levels before or after surgery and before or after chemoradiotherapy were correlated with the prognosis. Preoperatively, 99 of 114 patients (87%) had normal levels of hemoglobin compared with only 20 of 107 patients (19%) postoperatively. At the onset of radiochemotherapy, the hemoglobin levels of 82 of 116 patients (71%) were within the normal range. After radiochemotherapy, however, 62 of 114 patients (54%) had normal hemoglobin levels. Univariate analysis (Kaplan-Meier method and log-rank test) showed that patients with decreased pre- or postoperative hemoglobin levels had significantly worse locoregional control ( P=0.032 and P=0.0001, respectively) and lower overall survival ( P=0.0013 and P=0.0002, respectively) than patients with normal hemoglobin levels. The 3-year locoregional control rates in patients with preoperative hemoglobin levels that were normal, were reduced by 1-2 g/dl or were reduced by more than 3 g/dl, respectively, were 78%, 55% and 50%. Correlated with normal and diminished postoperative hemoglobin levels, the 3-year locoregional control rates were 90%, 84% and 50%, respectively. There was no correlation between prognosis and hemoglobin level at the onset or after radiochemotherapy. On multivariate analysis, only the postoperative hemoglobin level remained a prognostic factor for locoregional control ( P=0.0241) and overall survival ( P=0.0080). We conclude that low postoperative hemoglobin levels resulting from blood loss may influence the efficacy of postoperative radiochemotherapy in patients with head and neck cancer. Early intervention to raise the postoperative hemoglobin level may result in better tumor control and overall survival after combined-modality therapy.

Hyperfibrinogenemia as a risk factor for sudden hearing loss.

OBJECTIVE: To clarify predisposing conditions for vascular events. SETTING: Vascular events, immunologic processes, and viral infections have to be considered as pathomechanisms for most cases of sudden hearing loss. STUDY DESIGN: Hemorrheologic parameters were studied in 53 patients with sudden hearing loss within 5 days of the onset. PATIENTS: A control group of 53 normal-hearing people was matched pairwise according to age and gender. RESULTS: Fibrinogen levels were significantly higher in patients with sudden hearing loss (343 +/- 98 mg/dl) than in control subjects (303 +/- 69 mg/dl). Erythrocyte aggregation (27.3 +/- 5.6 a.u. versus 20.9 +/- 8.5 a.u.) and plasma viscosity (1.31 +/- 0.13 mPa/s versus 1.26 +/- 0.08 mPa/s) in patients with SHL were also significantly higher than in control subjects. No significant difference could be found in the parameters of clinical chemistry, hematology, and hemostasias investigated. CONCLUSION: Because elevated plasma fibrinogen plays a major role in cardiovascular diseases such as myocardial infarction and stroke, it is possible that this plasma protein is also involved in the pathogenesis of sudden hearing loss of vascular origin. More research is still required to determine the value of measuring plasma fibrinogen levels in clinical practice and identifying hyperfibrinogenemia in sudden hearing loss.