Comparison of HPV prevalence in HNSCC patients with regard to regional and socioeconomic factors.

HPV infection is considered as an independent risk factor for head and neck squamous cell carcinomas (HNSCC). Due to highly variable prevalence results in numerous studies, it is, however, difficult to estimate the relevance of HPV infection as risk factor for a specific patient collective. This study aimed to elucidate the disparities of HPV prevalence by analyzing socioeconomically and regionally different patient collectives. Two age, gender, stage and tumor location matched cohorts of 18 private health insured (PHIP) and 16 statutory health insured patients (SIP) suffering from an oropharyngeal squamous cell carcinoma (OSCC) and treated at a university hospital were screened for p16 overexpression and HPV infection by immunohistochemistry and PCR. In addition 85 HNSCC patients of an otolaryngology private practice (PPP) in a rural area were screened for p16 overexpression and positive cases were tested for HPV infection. HPV prevalence was 72.2% in the PHIP collective in comparison to 25.0% (p = 0.015) in the SIP collective with a significantly improved 5-year overall survival (p = 0.003) of the PHIP collective. The total HPV prevalence of PPP group was 7.1% with the highest infection rate in tonsillar carcinomas (33.3%) and a larger percentage of female patients in the HPV positive group (p = 0.037). This study shows that variable HPV infection rates in HNSCC can be caused by the selection of particular patient collectives, which suggest taking socioeconomic and regional factors into account for a decision on HPV testing, if it is not performed on a routine basis.

Sudden sensorineural hearing loss: systemic steroid therapy and the risk of glucocorticoid-induced hyperglycemia.

Sudden sensorineural hearing loss is usually treated with systemic glucocorticoids. Intratympanic injections of glucocorticoids offer a possibly equivalent treatment alternative, avoiding adverse systemic effects on blood glucose. We, therefore, investigated the extent to which different doses of systemic glucocorticoid therapy affects blood glucose levels. We conducted a retrospective analysis of treatment courses in 179 patients from the Departments of Otorhinolaryngology, Ophthalmology and Dermatology who underwent short-course systemic glucocorticoid therapy. Patients were subdivided into three groups on the basis of their cumulative prednisolone dose from days 1 to 3 (Group 1: <750 mg; Group 2: 750-1,499 mg; Group 3: >1,499 mg); in addition, a distinction was made between diabetic and non-diabetic patients. Among the non-diabetic patients on days 2-4, diabetic levels of fasting blood glucose were detected significantly more often (P < 0.01) in Group 3 (67 %) than in Group 1 (28 %) and Group 2 (21 %). Furthermore, there was a highly significant mean Pearson correlation (r = 0.329; P < 0.01) between blood glucose levels and glucocorticoid dose. This correlation was even more pronounced in the diabetic patients (r = 0.51; P = 0.02). In this category, hyperglycemia was detected in 40 % of patients in Group 1, 63 % in Group 2 and 100 % in Group 3. The prevalence of glucocorticoid-induced hyperglycemia during systemic therapy is high and rises as the dose increases. This should be kept in mind when choosing the dosage. Besides, it should also be considered that even short-term hyperglycemia presents possible health risks and the risk of inducing diabetes. This is especially of interest as intratympanic therapy offers a possible alternative to the systemic application.

Effects of botulinum toxin a on cytokine synthesis in a cell culture model of cutaneous scarring.

OBJECTIVE: To evaluate possible botulinum toxin A effects in a cell culture model. METHODS: In a cell culture model with dermal fibroblasts and microvascular endothelial cells, possible botulinum toxin A effects were evaluated. Cell proliferation and cytokine expression were analyzed using viability assays and enzyme-linked immunosorbent assay techniques. RESULTS: Neither cell proliferation nor cytokines and growth factors (interleukin 6, monocyte chemoattractant protein 2, fibroblast growth factor, macrophage colony-stimulating factor, and vascular endothelial growth factor) were affected by botulinum toxin A incubation. CONCLUSIONS: The present data do not add evidence to suggest a significant therapeutic role of botulinum toxin A injections for cutaneous wound healing beyond chemoimmobilization. Further studies that include patient-specific cells of hypertrophic scars are required to better understand what role botulinum toxin A can play in the treatment of mature scar tissue.

Repetitive transcranial magnetic stimulation for tinnitus treatment: no enhancement by the dopamine and noradrenaline reuptake inhibitor bupropion.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has shown beneficial effects in patients with chronic tinnitus. Recent preclinical data in healthy controls suggest that the effects of low-frequency rTMS can be enhanced by dopaminergic drugs. OBJECTIVE: We investigated whether application of the dopamine reuptake inhibitor bupropion increases the clinical effects of low-frequency rTMS over the auditory cortex in tinnitus patients. SUBJECTS AND METHODS: Eighteen subjects with chronic tinnitus received 10 sessions of 1 Hz rTMS (2000 pulses/day, 110% motor threshold) applied to the left temporal cortex. In addition, these subjects received one dosage of 150 mg bupropion (Wellbutrin XL/Elontril) 4 hours before each TMS session. Treatment outcome was assessed with a tinnitus questionnaire over a 3-month period. Treatment effects were compared with a control group of 100 tinnitus patients matched for age, tinnitus duration, and tinnitus questionnaire baseline scores, who received the same rTMS treatment without prior bupropion application. RESULTS: For the whole sample, there was a significant effect of rTMS treatment over time. There were no significant differences between the bupropion and the control group. CONCLUSIONS: Our data suggest that 150 mg bupropion administration does not enhance the effect of rTMS in the treatment of tinnitus.

Curing tinnitus with a Cochlear Implant in a patient with unilateral sudden deafness: a case report.

Cochlear implantation is a routine procedure for patients with bilateral profound sensorineural hearing loss. Some reports demonstrated a suppression of tinnitus as a side-effect after implantation. We describe the case of a 55-year-old man suffering from severe right-sided tinnitus in consequence of sudden right-sided deafness. Multiple therapeutic efforts including intravenous steroids and tympanoscopy with grafting of the round window remained unsuccessful. One year after onset of symptoms right-sided cochlear implantation was performed, which resulted in a complete abolishment of tinnitus after activating the implant. Severe unilateral tinnitus after sudden deafness might represent a new indication for cochlear implantation.

Levodopa does not enhance the effect of low-frequency repetitive transcranial magnetic stimulation in tinnitus treatment.

OBJECTIVE: Low-frequency repetitive transcranial magnetic stimulation (rTMS) has shown promise for the treatment of tinnitus. Experimental data from motor cortex stimulation in healthy subjects indicate that the suppressing effect of low-frequency rTMS can be enhanced by dopaminergic receptor activation. Here we investigated whether administration of the dopamine precursor levodopa before low-frequency rTMS enhances its efficacy in tinnitus treatment. STUDY DESIGN: Sixteen patients with chronic tinnitus received 100 mg of levodopa before each session of low-frequency rTMS. Results were compared with a matched control group of 16 patients who received the same treatment, but without levodopa. Treatment outcome was assessed with a standardized tinnitus questionnaire. RESULTS: Both stimulation protocols resulted in a significant reduction of tinnitus scores after 10 days of stimulation; however, there was no significant difference between the two groups. CONCLUSION: Our data suggest that 100 mg of levodopa does not enhance the effect of rTMS in the treatment of tinnitus.

Combined temporal and prefrontal transcranial magnetic stimulation for tinnitus treatment: a pilot study.

OBJECTIVES: Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been proposed as a new treatment strategy for patients with chronic tinnitus. However, functional abnormalities in tinnitus patients also involve brain structures used for attentional and emotional processing, such as the dorsolateral prefrontal cortex. Therefore, we have developed a new rTMS treatment strategy for tinnitus patients that consists of a combination of high-frequency prefrontal and low-frequency temporal rTMS. STUDY DESIGN: A total of 32 patients received either low-frequency temporal rTMS or a combination of high-frequency prefrontal and low-frequency temporal rTMS. Treatment effects were assessed with a standardized tinnitus questionnaire (TQ). RESULTS: Directly after therapy there was an improvement of the TQ-score for both groups, but no differences between groups. An evaluation after 3 months revealed a remarkable benefit from the use of combined prefrontal and temporal rTMS treatment. CONCLUSION: These results support recent data that suggest that auditory and nonauditory brain areas are involved in tinnitus pathophysiology.

Which tinnitus patients benefit from transcranial magnetic stimulation?

OBJECTIVES: Chronic tinnitus is associated with hyperactivity of the central auditory system. Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been proposed as a treatment for chronic tinnitus. This study determined the factors that predict a beneficial outcome with rTMS treatment. STUDY DESIGN: Forty-five patients with chronic tinnitus underwent 10 sessions of low-frequency rTMS to their left auditory cortex. The treatment outcome was assessed with a tinnitus questionnaire. Therapeutic success was related to the patients' clinical characteristics. RESULTS: A significant reduction in tinnitus complaints occurred after rTMS. In the questionnaire, 40% of the patients improved by five points or more. Treatment responders were characterized by shorter duration of tinnitus complaints and no hearing impairment. CONCLUSION: Tinnitus-related neuroplastic changes might be less pronounced in patients with normal hearing and a short history of complaints. This could explain why those patients benefitted more from rTMS treatment.

Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus.

OBJECTIVES: The pathophysiologic mechanisms of idiopathic tinnitus remain unclear. Recent studies demonstrated focal brain activation in the auditory cortex of patients with chronic tinnitus. Low-frequency repetitive transcranial magnetic stimulation (rTMS) is able to reduce cortical hyperexcitability. STUDY DESIGN: Fusing of the individual PET-scan with the structural MRI-scan (T1, MPRAGE) allowed us to identify exactly the area of increased metabolic activity in the auditory cortex of patients with chronic tinnitus. With the use of a neuronavigational system, this target area was exactly stimulated by the figure 8-shaped magnetic coil. In a prospective study, rTMS (110% motor threshold; 1 Hz; 2000 stimuli/day over 5 days) was performed using a placebo controlled cross-over design. Patients were blinded regarding the stimulus condition. For the sham stimulation a specific sham-coil system was used. Fourteen patients were followed for 6 months. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). SETTING: Tertiary referral medical center. RESULTS: Increased metabolic activation in the auditory cortex was verified in all patients. After 5 days of verum rTMS, a highly significant improvement of the tinnitus score was found whereas the sham treatment did not show any significant changes. The treatment outcome after 6 months still demonstrated significant reduction of tinnitus score. CONCLUSION: These preliminary results demonstrate that neuronavigated rTMS offers new possibilities in the understanding and treatment of chronic tinnitus.

Benefits of bilateral electrical stimulation with the nucleus cochlear implant in adults: 6-month postoperative results.

OBJECTIVE: To evaluate the benefits of bilateral electrical stimulation for hearing-impaired adult subjects using the Nucleus 24 cochlear implant in a multicenter study, and to compare and quantify performance on speech perception measures in quiet and in noise and localization ability for unilateral and bilateral cochlear implant use. DESIGN: : Repeated single subject measures were carried out for each subject, with each subject serving as their own control. Assessment of unilateral and bilateral listening conditions for performance on tests of speech comprehension and sound localization were performed. Speech comprehension measures were performed in quiet at 0 degree azimuth and in the presence of background noise simultaneously presented from the same speaker and spatially separated by 90 degrees, at S+45 degrees N45 degrees and at S-45 degrees N+45 degrees . Test materials included Freiburger monosyllabic words, Oldenburger sentences, and the Hochmair-Schulz-Moser sentences. Tests of localization were performed in the horizontal plane with 12 speaker locations 30 degrees apart using a shortened sentence stimulus from the Hochmair-Schulz-Moser sentences at two possible presentation levels of 55 and 70 dB sound pressure level for assessment of directionality. The binaural advantage provided by bilateral stimulation was calculated with respect to each ear separately, classified as either the better or poorer performing ear for each speech material in quiet and in noise test conditions. For localization of sound, the binaural advantage was compared with left and right ears separately. Paired comparisons for performance data in all conditions were carried out by considering measurements for each subject in different conditions as paired observations and applying the Student's t test to determine the statistical difference between the data sets. SETTING: Tertiary referral centers with a cochlear implant program. PATIENTS: Thirty-seven profoundly hearing-impaired adults were enrolled in the study, 22 simultaneously and 15 sequentially bilaterally implanted. All patients received the Nucleus 24 cochlear implant and used the Nucleus SPrint or ESPrit 3G speech processor, with the vast majority using the ACE speech coding strategy. RESULTS: For spatially separated speech in noise conditions, an interaural performance advantage for the ear closest to the speech source (i.e., with a superior signal to noise ratio) compared with that for the ear closest to the noise source (i.e., with an inferior signal to noise ratio) is consistently demonstrated regardless of whether it is the better or poorer performing ear closest to the speech signal. This is referred to as a significant binaural head-shadow benefit, resulting in a mean improvement between -10 dB and -11.4 dB in the critical signal to noise ratio required for 50% speech comprehension for the Olden-burger sentences and a mean improvement in the maximum score of 42% to 55% for the ear closest to the speech signal over the ear farthest away for the Hochmair-Schulz-Moser sentences. Bilateral stimulation is always observed to provide a performance advantage over the unilateral listening condition for either ear when ipsilateral to the noise source. In addition, as demonstrated by approximately half the subjects tested in noise with the Hochmair-Schulz-Moser sentences, a performance advantage of bilateral stimulation may be observed over the better ear alone when positioned ipsilateral to the speech signal, which is referred to as a binaural squelch effect. On average, for the group, this resulted in a statistically significant improvement in speech comprehension scores of 8% in the bilateral listening condition compared with the scores for the better ear alone. Through assessment of comprehension of coincidental speech in noise and speech in quiet, a significant benefit of binaural redundancy was noted for the group for Oldenburger sentence scores in noise and in quiet compared with unilateral scores for either ear and for the Freiburger monosyllabic words in quiet in comparison with the better ear alone scores. Binaural stimulation also led to a significant improvement in localization ability over either monaural condition, with the root mean square degrees of error reduced by 38 degrees compared with that observed for unilateral stimulation. CONCLUSION: Similar to what has been observed for bilateral acoustic stimulation in the past, bilateral electrical stimulation provides the foundation for the potential advantages of the head-shadow effect, providing a binaural head-shadow benefit and binaural auditory processing such as binaural redundancy and binaural squelch effects, all of which combine to lead to improved speech comprehension over unilateral listening conditions. The combination of improved speech comprehension and improved localization ability made available through bilateral electrical stimulation provides the necessary foundation to further assist the hearing-impaired listener to better cope with communication in the everyday listening situation both in noise and in quiet.