Steffen Maune

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°N45° and at S−45°N+45°. 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.

New insights into the pathophysiology of primary acquired dacryostenosis

OBJECTIVE To obtain new insights into the pathophysiology of primary acquired dacryostenosis. DESIGN Comparative autopsy tissue study with histopathologic correlations. MATERIALS Tissue specimens from the human nasolacrimal ducts of 36 patients undergoing endonasal dacryocystorhinostomy within a framework of primary acquired dacryostenosis were analyzed by histologic studies and electron microscopic examination. Six lacrimal systems of body donors served as controls. TESTING One group of tissue specimens from each lacrimal system was prepared and processed with paraffin, sectioned, stained by different methods, and finally examined by light microscopy. The other group was processed with araldite after preparation, sectioned semithin and ultrathin, and examined by transmission electron microscopy. MAIN OUTCOME MEASURES The degree of dacryostenosis was scored in each tissue specimen by grading the histologic sections as mild (active chronic inflammation), moderate (proliferative sclerotic forms of chronic fibrosis), or severe (total subepithelial fibrosis). RESULTS Of 36 patients with epiphora, 13 had functional obstruction with a patent lacrimal system on syringing; in 23 cases, the lacrimal passage was completely obstructed. Different pathologic stages correlating to duration of symptoms were found ranging from active chronic inflammation to proliferative sclerotic forms and total subepithelial fibrosis. CONCLUSIONS Descending inflammation from the eye or ascending inflammation from the nose initiates swelling of the mucous membrane, remodeling of the helical arrangement of connective tissue fibers, malfunctions in the subepithelial cavernous body with reactive hyperemia, and temporary occlusion of the lacrimal passage. In the follow-up, repeated isolated occurrence of dacryocystitis leads to structural epithelial and subepithelial changes, which may lead either to a total fibrous closure of the lumen of the efferent tear duct or to a nonfunctional segment in the lacrimal passage that is manifest on syringing.

Metalloproteinases and their inhibitors: influence on tumor invasiveness and metastasis formation in head and neck squamous cell carcinomas.

Matrix metalloproteinases (MMPs) play an important role in tumor invasiveness. This study investigates the expression status of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in head and neck squamous cell carcinomas (HNSCC).

The role of RANTES in nasal polyposis.

Background Characteristic infiltrates of eosinophils are a hallmark of nasal polyps (NPs). Several studies suggest that members of the CC chemokine family may be involved in this process. RANTES (regulated on activation, normal t-cell-expressed and secreted) is a member of the CC chemokine family with chemotactic activity on mainly eosinophils and T lymphocytes. Thus, RANTES is an interesting target for the recruitment of eosinophils and T lymphocytes into the nose. The degree of the tissue eosinophilia has been reported to correlate with the severeness of the symptomatology of the disease and the extension on the lower respiratory tract, as well as with the probability of the recurrence of NPs. Therefore, we hypothesized that high numbers of eosinophils correlate with high levels of RANTES and that associated atopic diseases modify this correlation. Methods Total RNA was extracted from NP homogenates, reverse transcribed and RANTES mRNA expression analyzed using semiquantitative reverse transcription polymerase chain reaction and Northern blot analysis. Histological studies divided NPs in an eosinophilic and low eosinophilic group. Additionally, RANTES protein concentration was measured in homogenates by a RANTES-specific enzyme-linked immunosorbent assay. Results This study has clearly shown that RANTES is expressed and secreted in NPs. The group with a high tissue eosinophilia had a significant higher RANTES gene expression and protein production than NPs without tissue eosinophilia. The isolated coincidence of acetylsalicyl acid intolerance with chronic hyperplastic sinusitis/NP additionally increased significantly the RANTES amounts in NPs. Conclusion Increased RANTES leads to increased tissue eosinophilia. Associated acetylsalicylic acid intolerance seems to enhance the amount of RANTES in NPs and might explain in part the more severe clinical course in those patients. Thus, RANTES appears to play an important role in mobilization of eosinophils into the local inflamed tissue.

RANTES Production by Cytokine–Stimulated Nasal Fibroblasts: Its Inhibition by Glucocorticoids

Nasal fibroblasts play an important role in both nasal polyposis and nasal allergic diseases and they are known to release a number of proinflammatory cytokines, including GM–CSF, IL–8 and IL–6. The aim of this present work was to investigate whether cytokine–stimulated nasal fibroblasts release biologically active RANTES as well as to study the effect of corticosteroids on the ability of nasal fibroblasts to produce the cytokine. Measurements of RANTES by ELISA demonstrated that RANTES is constitutively secreted spontaneously (21±4 vs. 19±6 ng/ml, respectively p>0.05). Stimulation of these cells with either TNF–α, IL–1β or IFN–γ induce further release of RANTES in a dose–dependent manner with TNF–α being the most potent stimulus. RANTES mRNA expression in nasal fibroblasts correlated with the amount of protein released in the culture supernatant upon cytokine stimulation. Moreover, chemotaxis studies demonstrated that the nasal–derived RANTES was biologically active on eosinophils. Betamethasone and hydrocortisone were found to downregulate RANTES mRNA expression in TNF–α–stimulated fibroblasts. These observations suggest that RANTES released by nasal fibroblasts may regulate eosinophil recruitment in nasal disease while glucocorticoids may inhibit the influx of these cells by suppressing the production of RANTES.

Psoriasin (S100A7) is a principal antimicrobial peptide of the human tongue

The human tongue is particularly resistant to bacterial infections although the mouth is continuously exposed to a complex and abundant ensemble of microbes, such as the common intestinal bacterium Escherichia coli. We show that lingual epithelia produce and release, as a primary E. coli-killing compound, the S100 protein psoriasin. No significant reduction in psoriasin release could be achieved through repeated rinsing of the epithelial surface of the tongue. Psoriasin is produced in the upper layers of the lingual epithelia but is lacking in the most superficial and basal cells. It displays a gradient pattern of expression with decreasing expression from the anterior one-third to the posterior portion of the tongue. Thus, psoriasin may be the key to the resistance of the human tongue toward E. coli.

The primary role in biologic activity of the neutrophil chemokines IL-8 and GRO-α in cultured nasal epithelial cells

Primary nasal epithelial cells were investigated for their ability to synthesize and deliver neutrophil chemotactic factors (chemokines) following tumor necrosis factor-alpha (TNF-alpha) induction. The chemokines interleukin8 (IL-8), growth-related oncogene-alpha (GRO-alpha), epithelial cell-derived neutrophil attractant-78 (ENA-78), and granulocyte chemotactic protein-2 (GCP-2) have been detected and characterized and shown to have different potencies in the chemotaxis of neutrophils. Cultures of primary nasal epithelial cells were treated with TNF-alpha in concentrations of 20 and 200 ng/ml for 2, 8, 24, and 72 h. The chemokine protein concentrations in the supernatants of the incubations were determined by the ELISA technique. Chemokine mRNA expression in epithelial cells was also measured using the reverse transcriptase-polymerase chain reaction (RT-PCR). The biologic activity of the chemokines was identified using a three-step high-performance liquid chromatography (HPLC) technique, a bioassay involving measurement of neutrophil chemotaxis in a single Boyden chamber. Both the IL-8 and GRO-alpha proteins and their respective mRNA appear to be induced by TNF-alpha in epithelial cells. The chemotactic responsiveness of both GRO-alpha and IL-8 appears to predominate after 24 h incubation with TNF-alpha. The chemokines GCP-2 and ENA-78 were only weakly induced by TNF-alpha. The neutrophil chemokines IL-8 and GRO-alpha were synthesized in nasal epithelial cell culture induced by TNF-alpha in biologically active concentrations of 0.8 ng/ml and 1.42 ng/ml, respectively. It appears that both the IL-8 and GRO-alpha chemokines may contribute to neutrophil tissue migration in sinusitis, whereas GCP-2 and ENA-78 are of secondary importance to the chemotaxis of neutrophils in this condition.

Zenker's diverticulotomy with the carbon dioxide laser: perioperative management and long-term results.

We analyzed 119 files of patients with Zenkers diverticulum who were treated with CO2 laser systems concerning treatment management, complications, and long-term results. Although the tissue bridge was dissected down to the fundus of the diverticulum, opening the mediastinum, mediastinitis was observed in none of the cases. Of the patients followed up for long-term results, 90.3% were completely symptom-free, and 5.8% of the patients reported an improvement in general condition. In view of the low rate of complications and the low level of morbidity and because of the good functional results, microendoscopic laser surgical diverticulotomy can be recommended as suitable therapy, especially as compared to external approaches or even other endoscopic treatment strategies. The main advantage as compared to staple-assisted esophagodiverticulostomy is that no special equipment is needed and that even small pouches can be treated successfully.

Geographical and anatomical influences on human papillomavirus prevalence diversity in head and neck squamous cell carcinoma in Germany

The increased knowledge regarding HPV-infections in head and neck squamous cell carcinoma (HNSCC) has unexpectedly contributed to several uncertainties related to i) prevalence diversities depending on tumour site and geographical origin of the patients, ii) proportion of HPV-driven tumours among HPV-DNA-positive cases, and iii) identification of patients with HPV-attributed survival benefit. To investigate this heterogeneity, we analysed 307 HNSCC cases (tonsillar, n=135; non-tonsillar, n=172) from eight health care centers mostly from Northern Germany and determined HPV-DNA/mRNA and p16INK4A-status and combined results with the patient outcome. Overall HPV-DNA prevalence rate was 23.5% (72/307); attributed to: 43.7% (59/135) and 7.6% (13/172) tonsillar and non-tonsillar cases, respectively. Among these, 96.6% tonsillar and 38.5% non-tonsillar SCC were HPV-mRNA-positive. Although the study cohort was composed of patients from regions of rather close proximity, prevalence rates showed diversities of up to 40% in HNSCC subsite analysis with the lowest prevalence for tonsillar SCC in metropolitan areas (22.2%) vs. 50.9% in rural areas. Survival analysis identified p16INK4A alone as strongest predictor, followed by HPV-DNA-status alone or in combination with p16INK4A. This survival benefit was shown for tonsillar and non-tonsillar cases. Smoking significantly correlated with HPV-status, however, it does not influence survival when stratified for HPV. In conclusion, the data emphasize the urge for further data on HPV-infection in HNSCC to, e.g. clarify to what extent survival benefits of p16INK4A-positive patients are truly attributed to HPV-infections.

Defensin and chemokine expression patterns in the palatine tonsil : a model of their local interaction

Defensins and chemokines are an essential part of the immune response mechanisms in the head and neck mucosa. This work investigates their correlation and their expression pattern in tonsillar disease. Forty-four tonsil tissue samples were obtained from patients who underwent tonsillectomy between 1998 and 1999 for chronic tonsillitis with ( n =9) and without ( n =25) inflammatory infiltrates and hyperplasia of the tonsil ( n =10). Defensin (hBD-1, hBD-2, HNP-1 and HNP-4) and chemokine (RANTES, eotaxin, eotaxin-2, MCP-3, MCP-4 and IL-8) mRNA expressions were analyzed by SQRT-PCR. HNP-4 and eotaxin-2 expressions were positively correlated ( P <0.05) in the acute tonsillitis group. HBD-2 and MCP-3 expressions were positively correlated in the hyperplastic tonsils group. Within all groups together, HNP-4 and RANTES expressions were highly positively correlated ( P <0.01), and HNP-1 and hBD-2 were positively correlated with IL-8 expressions. Immunohistochemistry demonstrated eotaxin-1 as well as IL-8 production to be predominantly located within the lymphoid follicles and submucosa. RANTES production was shown in the epithelial lining and perivascular tissue. The expression of hBD-1 and hBD-2 was limited to the epithelial lining. Our data support an association between the innate and acquired immune systems on the defensin-chemokine level. The finding of positively correlated hBD-2 and IL-8 expression is biologically relevant because of the proximity of hBD-2 (epithelium) and IL-8 (submucosa) release, as well as the synergistic support of the Th1 system. In addition, our data suggest RANTES as a first-line mediator of perivascular leukocyte recruitment.