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Hypothesis: Trans-tympanic Rosmarinic Acid (RA), as compared with the systemic administration, protects against noise-induced auditory hair cell and hearing losses in rats in vivo., Background: ROS production, lipoperoxidative damage, and an imbalance of antioxidant defences play a significant role in noise-induced hearing loss. Several molecules with antioxidant properties have been tested to restore redox homeostasis; however, drug delivery system represents a challenge for their effectiveness. In our model, acute and intense noise exposure induces hearing loss, hair cell death, and oxidative stress, with an increase in superoxide production and over-expression of lipid peroxidation in cochlear structures., Methods: RA was administrated in male Wistar rats by trans-tympanic (20 μl) and systemic (10 mg/kg) modality. In systemic administration, RA was injected 1 hour before noise exposure and once daily for the following 3 days. ABRs were measured before and at days 1, 3, 7, and 30 after noise exposure. Rhodamine-phalloidin staining, dihydroethidium and 8-isoprostane immunostainings were performed to assess and quantify outer hair cells loss, superoxide production, and lipid peroxidation in the different experimental groups., Results: Systemic RA administration significantly decreased noise-induced hearing loss and the improvement of auditory function was paralleled by a significant reduction in cochlear oxidative stress. The trans-tympanic modality of drug administration showed a similar degree of protection both at the functional and morphological levels., Conclusion: The effectiveness of RA given via trans-tympanic injection could be interesting for the future application of this minimally-invasive procedure in the treatment of ROS-induced hearing loss.

Study Design: We investigate on the surgical reliability of nasal palatine line for the transnasal approach and introduce a conceptually analogue radiological line as a reliable predictor of the maximal superior extension of the transoral approach. We have also compared radiological and surgical lines to find possible radiological references points to predict preoperatively the maximal extent of superior dissection for the transoral approach., Objective: After comparing the surgical exposition angle and the working channel volume of both the approaches in our previous article, now we compare the radiological (theoretical) with the "surgical" (effective) Nasopalatine line and the latter with the recently introduced Nasal Axial Line. We conceived a radiological line with a similar significance for the transoral approach and we called it Mandibulopalatine line; then we compared the radiological with the "surgical" one., Summary of Background Data: Endoscopy represents both an alternative and a useful complement to the standard microsurgical approach to the anterior craniovertebral junction (CVJ). Both the surgical routes have a limitation caused by the hard palate., Methods: Ten fresh nonperfused cadavers were studied. Transnasal and transoral linear and angled exposure of the CVJ were evaluated by means of X-ray and CT scan in the sagittal plane., Results: The angular difference between the radiological and surgical transoral endoscopic lines was significantly smaller compared with the difference between the radiological and surgical transnasal lines. Finally we found how to calculate preoperatively the "surgical" (effective) Mandibulopalatine line by a simple lateral preoperative radiological study of the CVJ., Conclusion: Naso-axial line is confirmed to be a reliable preoperative predictor of the maximal extent of inferior dissection for transnasal approach. Surgical Palatine Inferior dental Arch line will draw the maximal extent of superior dissection for the transoral approach with simple lateral head X-ray examination by open mouth., Level of Evidence: 3.

Hypothesis: To investigate whether curcumin may have in vivo protective effects against cisplatin ototoxicity by its direct scavenger activity and/or by curcumin-mediated upregulation of HO-1., Background: Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. A protective approach to decrease cisplatin ototoxicity without compromising its therapeutic efficacy remains a critical goal for anticancer therapy. Recent evidences indicate that curcumin exhibits antioxidant, anti-inflammatory, and chemosensitizer activities., Methods: In male adult Wistar rats, a curcumin dose of 200 mg/kg, selected from a dose-response curve, was injected 1 hour before cisplatin administration and once daily for the following 3 days. A single dose of cisplatin (16 mg/kg) was administered intraperitoneally. Rats were divided as follows: 1) control, 2) curcumin control, 3) vehicle control, 4) cisplatin, 5) cisplatin+ vehicle, and 6) curcumin+cisplatin. ABRs were measured before and at Days 3 and 5 after cisplatin administration. Rhodamine-phalloidin staining, 4-hydroxy-2-nonenal and heme-oxigenase-1 immunostainings, and Western blot analyses were performed to assess and quantify OHC loss, lipid peroxidation, and the endogenous response to cisplatin-induced damage and to curcumin protection., Results: Curcumin treatment attenuated hearing loss induced by cisplatin, increased OHC survival, decreased 4-HNE expression, and increased HO-1 expression., Conclusion: This preclinical study demonstrates that systemic curcumin attenuates ototoxicity and provides molecular evidence for a role of HO-1 as an additional mediator in attenuating cisplatin-induced damage.

Purpose of Review: Overall survival of head and neck squamous cell carcinoma patients on the whole has not dramatically improved in the last 30 years. One of the reasons is that tumour, node, metastasis classification is probably in some cases inadequate, since similar cases under a clinico-pathological point of view, may differ widely in prognosis. The most important reason for this is probably the extreme biological heterogeneity, which leads to a lack of consistency in treatment planning. The aim of the present review is to delineate the advances and the perspectives of clinical use of molecular characterization, which is an attempt to break through such molecular heterogeneity and to define, together with tumour, node, metastasis classification, homogeneous groups of patients for prognostic stratification and treatment selection., Recent Findings: Among the markers evaluated in the last years, some have revealed particular promise. Epidermal growth factor receptor is probably the most reliable molecular marker at present, retaining its prognostic value independently from primary treatment. The p53 gene, the p53 protein being the main effector of DNA damage induced apoptosis, is probably the best predictor of radio/chemosensitivity., Summary: Even if clinical tumour, node, metastasis classification will probably retain its significance, it is now becoming possible, by molecular markers, to acquire biological information about host and tumour, to break through the above-cited molecular heterogeneity and eventually to optimize the choice of treatment.

Objectives: We investigated the association of idiopathic sudden sensorineural hearing loss (ISSNHL) with coenzyme Q (CoQ) and cardiovascular risk factors., Study Design: A prospective study., Setting: Hospital center., Patients: Thirty Italian patients with ISSNHL and 60 healthy Italian subjects., Intervention: Diagnostic., Main Outcome Measures: Evaluation of serum CoQ levels and cardiovascular risk factors (total cholesterol, low-density lipoprotein [LDL], homocysteine [HCY]). The results were compared with variance analysis and Student's t test. Univariate and multivariate analysis were used to evaluate the association between ISSNHL and CoQ, total cholesterol, LDL, and HCY levels., Results: In our series, we found a significant association between ISSNHL and high total cholesterol (p < 0.05), high LDL (p = 0.021), and low CoQ (p < 0.05) levels. We did not find a significant association between ISSNHL and HCY levels. In the univariate analysis, low levels of CoQ, high levels of total cholesterol, and LDL were found to be significantly associated with ISSNHL. In the multivariate analysis, only high levels of total cholesterol and low levels of CoQ remained significantly associated with a high risk of sudden sensorineural hearing loss., Conclusion: The studies regarding the role of cardiovascular risk factors in ISSNHL are not conclusive. This is the first report regarding the association of ISSNHL and low serum levels of the antioxidant CoQ. Further studies are needed to investigate the role of antioxidants, including CoQ, in ISSNHL.

Hypothesis: To investigate the association between glutathione S-transferase (GST) gene polymorphisms and sudden sensorineural hearing loss (SSNHL) in a population of consecutive Italian patients. Assuming that reactive oxygen species formation may play a role in inner ear damage, we investigated whether profiles of GSTs antioxidant enzymes M1 and T1 genotypes may be associated with the risk of SSNHL., Study Design: A prospective study in patients with SSNHL., Patients and Methods: We investigated 80 Italian patients with SSNHL for the frequency of GSTT1 and GSTM1 polymorphisms. Genotype distribution of all factors found in patients were compared with those of 80 healthy control subjects of the same ethnic background using chi and odds-ratio analysis. Statistical significance was accepted at a level of p < 0.05., Results: In our series, the frequencies of GSTM1 and GSTT1 null genotypes did not differ from those of the control subjects., Conclusion: The few studies regarding genetic polymorphisms of GSTs in SSNHL are not conclusive. Further studies are needed to investigate the role of antioxidants including GSTs in SSNHL and to provide the lacking information to improve our knowledge in the field before implementing the use of genetic polymorphism in the SSNHL medicine daily practice.

Idebenone is a synthetic analogue of coenzyme Q10 with antioxidant properties. The present study investigated the antioxidant activity of idebenone in the rescue of acoustic trauma. Noise-induced hearing loss was induced by exposing guinea pigs to a continuous pure tone and idebenone was injected intraperitoneally 1 h before noise exposure and once daily for 3 days. Guinea pigs treated with idebenone showed significantly smaller auditory threshold shifts than unprotected control animals. Missing and apoptotic cells were identified with scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. Protected animals presented a lesser extent of both apoptotic activation and hair cell loss in the organ of Corti. Our results suggest an antioxidant function of idebenone in protection from noise-induced hearing loss and provide a rationale for exploring therapeutic strategies in humans.

Purpose of Review: The purpose of this review is to summarize the recent understanding of the harmful effects of gastric and duodenal agents on mucosa of the upper aerodigestive tract in patients with duodeno-gastro-esophageal reflux., Recent Findings: The damaging action of duodeno-gastro-esophageal reflux on the gastro-esophageal mucosa and its potential etiological role in the development of many inflammatory and neoplastic patterns have been well documented in the literature. Recently, there has been increasing evidence that duodeno-gastro-esophageal reflux may also be related to several laryngeal disorders and clinical studies confirm that reflux after gastric resection may enhance the development of laryngeal malignancies. Finally, there have been experimental attempts to confirm that duodenal contents may contribute to inflammation and carcinogenesis in the pharynx or larynx, as it is known to do in the esophagus., Summary: The association between duodeno-gastro-esophageal reflux and laryngeal lesions is of great interest to otolaryngologists because it focuses attention on a new pathological entity that could be classified as biliary laryngopharyngeal reflux. This condition, as an acid one, seems to represent an important dangerous, endogenous risk factor involved in the pathogenesis of inflammatory, precancerous and neoplastic laryngeal lesions. For these reasons, particular attention is required in the future regarding the understanding of the local environment, individual susceptibility and clinical treatment. Finally, new antireflux therapy should be considered to control not only the acid gastric component of the refluxate but also the duodenal component.

Objective: To investigate the association between gastric surgery and cancer of the larynx., Summary Background Data: Biliary reflux is frequent after gastric surgery and may reach the proximal segment of the esophagus and the larynx. It is possible that duodenal content (consisting in bile acids, trypsin), together with pepsin and acid residues when gastric resection is partial, may cause harmful action on the multistratified epithelium of the larynx., Methods: A retrospective case-control study on subjects admitted between January 1987 and May 2002 in the same hospital in Rome was carried out. The study included 828 consecutive patients with laryngeal cancer (cases) and 825 controls with acute myocardial infarction. Controls were randomly sampled out of a total of 10,000 and matched with cases for age, sex, and year of admission. Logistic regression models were used to assess the role of gastric resection in determining laryngeal cancer risk while controlling for potential confounding factors., Results: Previous gastrectomy was reported by 8.1% of cases and 1.8% of the controls (P < 0.0001). A 4-fold association emerged between gastric surgery and laryngeal cancer risk (adjusted OR = 4.3, 95% CI: 2.4-7.9). The risk appeared strongly increased 20 years after surgery (OR = 14.8, 95% CI: 3.4-64.6). Heavy alcohol drinking (OR = 2.5, 95% CI: 1.8-3.5), smoking (OR = 4.7, 95% CI: 3.3-6.7), and blue-collar occupation (OR = 4.6, 95% CI: 3.2-6.7) were all independently associated with the risk of laryngeal cancer., Conclusions: Previous gastric surgery is associated with an increased risk of laryngeal cancer. A periodic laryngeal examination should be considered in long-term follow-up of patients with gastric resection.

Immunoscintigraphy with 111In-F(ab')2-anti-carcinoembryonic-antigen monoclonal antibody was performed in patients with primary head and neck tumours (n = 14), recurrences (n = 3) and suspected posttherapy lymph node metastases (n = 3). No false-positive but two false-negative results were obtained. Single photon emission tomography was performed 24 h after the intravenous administration of the radiopharmaceutical with a positive predictive value of 100% and a sensitivity of 90%. Only two very small (< 1 mm diameter) and necrotic primary tumours escaped detection, while the recurrences and lymph node metastases were always correctly diagnosed, in contrast to computerized tomography and ultrasound. Even though highly selective patients only were considered in the present research, the results do suggest that immunoscintigraphy may be usefully applied in all routine protocols for the study of head and neck cancer.

Auditory cortex stimulation was studied by 99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission tomography (SPET) in 11 patients with normal vestibular and auditory tests, as well as computed tomography. Markedly increased temporal and parietal blood flows were found in left brain cortex, contralateral to the stimulus. The right auditory areas showed moderate hyperactivity. The method might be useful for tonotopic mapping of auditory cortex, using various pure tonal stimuli.

Brain stem auditory evoked potentials were recorded from 26 normal subjects who listened to 100 ms clicks at 10, 20, 50, and 100 repetitions per second at varying intensities. A 0.5+/-0.3 ms shift of the V wave latency was observed between 10 clicks per second and 100 clicks per second; a lesser difference was found when the repetition rate was shifted between 10 to 50, 20 to 50, or 20 to 100 clicks per second. No significant differences were observed when the repetition rate moved from 10 to 20 or between 50 and 100 clicks per second. Whatever latency shifts were observed appeared to be independent of the stimulus intensity. Waveform morphology seemed to be the same between 10 and 20 clicks per second, with only minor changes observed at the 50 clicks per second rate. At 100 clicks per second a decrease or a complete disappearance of some components or both was seen. These changes are accounted for by peripheral phenomena for the most part, and a number of clinical applications are suggested based on these observations.