Mupirocin reduces ciliary beat frequency of human nasal epithelial cells.

Mupirocin is used worldwide for topical treatment of infected skin lesions, impetigo, and especially for nasal decolonization of patients with carriage of Staphylococci, including methicillin-resistant Staphylococcus aureus. Nevertheless, data regarding the effects of mupirocin on the nasal mucosa, in particular on ciliary beat frequency (CBF), is lacking to date. We tested the CBF of ciliated nasal epithelial cells under the influence of Mupirocin-calcium dissolved in tert-butyl alcohol (TBA) containing media in different concentrations comparable to clinical use. Ringer's lactate solution and TBA served as negative control. Cells were visualized with a phase contrast microscope, and the CBF was measured with the SAVA system's region of interest method. Mupirocin-calcium dissolved in TBA led to a statistically significant time- and concentration-dependent decrease in CBF compared to the negative control. TBA addition without mupirocin also led to a significant decrease in CBF, although to a lesser extent than mupirocin/TBA. In conclusion, CBF of human nasal epithelia is significantly reduced by mupirocin-calcium-containing solutions in therapeutic concentrations. Due to our results in this study, mupirocin as a nasal decolonization agent should be used only with care, with a strictly set medical indication, and additional care measures should be considered.

[Prophylactic antibiotic use in ENT surgery]. / Perioperative Antibiotikaprophylaxe in der HNO.

Surgical antibiotic prophylaxis (SAP) is defined as the administration of an antimicrobial agent prior to contamination in previously sterile spaces and fluid. SAP should not be confused with the therapeutic use of antibiotics. There are a growing number of studies with the goal of answering the question which patients benefit most from SAP during which specific surgical procedure. However, in the specific surgical field of head and neck surgery and otolaryngological surgery, there are only a few guidelines answering that question for specific procedures. The aim of this study was to analyze the evidence found in the literature and to develop a standard operating procedure, which specifically addresses head and neck and otolaryngeal surgical procedures.

[Perioperative antibiotic prophylaxis during standard interventions in ear, nose and throat medicine]. / Perioperative Antibiotikaprophylaxe bei Standardeingriffen in der HNO-Heilkunde.

BACKGROUND: The majority of standard interventions in otorhinolaryngology are classified as "clean contaminated" according to international classifications; correspondingly, no generally accepted recommendations regarding perioperative antibiotic prophylaxis (pAP) exist. The value of such pAP for these interventions remains unclear. Aim of the study was to assess the effects of pAP in selected standard otorhinolaryngologic procedures. MATERIALS AND METHODS: In August 2012 a standard operating procedure (SOP) was implemented, which lead to termination of routine pAP for the majority of standard operations. All patients included in this retrospective study had undergone a standard procedure (tonsil, septum or paranasal sinus surgery) during a period either 6 months before or 6 months after the inauguration of the SOP. The charts were reviewed for demographic factors, postoperative complications and length of hospital stay. RESULTS: The group before the inauguration of the SOP consisted of 316 patients (132 female, 184 male), aged 30±20 years. The group after the inauguration comprised 308 patients (128 female, 180 male), aged 31±19 years. For the entire patient collective, the termination of pAP led to a statistically significant increase in postoperative antibiotic treatment for all types of interventions tested. A statistically significant change in noninflammatory complications or the length of hospital stay was not detected. DISCUSSION: The termination of pAP during standard procedures in otorhinolaryngology is associated with an increase in postoperative antibiotic treatment but has no effect on other postoperative complications tested or the length of hospital stay.

Polyhexanide-containing solution reduces ciliary beat frequency of human nasal epithelial cells in vitro.

In ENT, polyhexanide-containing solutions are used to treat nasal infections caused by multiresistant bacteria like methicillin-resistant Staphylococcus aureus. Many forms of commercial nasal solutions containing polyhexanide exist, such as gels or solutions for topical use. Data regarding the influence of polyhexanide on ciliary beat frequency (CBF) are lacking to date. We tested the CBF of nasal ciliated epithelial cells under the influence of a commercially available polyhexanide-containing solution (Lavasept(®) Concentrate) in a therapeutic concentration (0.04, 0.02%). In addition, we tested the concentrations of 0.1 and 0.01%. Cells were visualized with a phase contrast microscope, and the CBF was measured with the SAVA system's region of interest method. Ringer's solution and macrogol served as negative controls. A therapeutic concentration of Lavasept significantly reduced CBF in a time- and concentration-dependent manner. After 1 min, the CBF was reduced from 8.90 ± 1.64 to 5.00 ± 3.72 Hz with a concentration of 0.04% (p value = 0.001). After 10 min, all cilia stopped beating. After 5 min, a 0.02% solution of Lavasept concentrate decreased CBF significantly from 8.64 ± 1.71 to 3.30 ± 3.27 Hz (p value < 0.001). In conclusion, CBF of human nasal epithelia is significantly reduced with the use of the polyhexanide-containing solution Lavasept in some therapeutic concentrations. Due to our findings in this study, Lavasept should be used on ciliated mucosa only with caution and in a concentration of 0.02%.

[Frequency-specific analysis of the hVOR Prior of Cochlear Implant Operation]. / Frequenzspezifische Untersuchung des hVOR im Vorfeld einer CI-Operation.

Dizziness is one of the most common postoperative complications after a cochlear-implant (CI) surgery. With our prospective, matched-paired controlled study, we could demonstrate that patients with distinctive sensorineural hearing loss--even without any complaints of dizziness--already have a reduced horizontal vestibular-ocular-reflex (hVOR). Compared to controls, CI patients presented with a significantly reduced gain. 9 out of 17 CI patients showed physiological results in rotatory testing and video head thrust testing. One patient presented with pathological results in both tests. Remarkably, there were 2 patients who presented with pathological head impulse testing but normal values in rotatory testing and 5 patients who showed normal gains in video head impulse testing but abnormal rotatory tests. These findings clearly show the importance of a differentiated, frequency-dependent pre-operative vestibular assessment including rotatory testing and video-head impulse testing. Additionally, only an accurate pre-operative vestibular testing allows evaluating possible post-operative dizziness related complications and should be documented precisely, also for forensic reasons. This is the key to differentiate post-operative dizziness from an pre-operatively existing vestibular disorder that possibly might not be clinically apparent by the time of testing.

[Functional and aesthetic therapy concepts of keloids in the head- and neck area]. / Funktionelle und ästhetische Therapiekonzepte von Keloiden im Kopf-Hals Bereich.

Keloids are fibroproliferative extreme variants of an impaired wound healing, developing a tumour-like growth. In the ENT area keloids arise mainly at auricle. Often caused by piercings or trauma. They grow bulging excessively over the original scar edges and adopt sometimes bizarre morphologies. The patients complain often of dysesthesias such as burning pain, severe itching and are suffering often from stigmatization. The huge number of therapy methods, for the treatment of keloids described in the literature (silicon therapy, compression, intralesional corticoids, intra- or extralesional surgical excision, kryosurgery, radiatio, Interferon- or Bleomycin-therapy) emphasize the enormous challenge for the treating doctor, particularly in facial plastic surgery.

[Correction of complex facial scars]. / Die Behandlung komplexer Narben im Gesicht.

Correction of complex facial scars frequently requires individualized, multimodal strategies, which are composed of various therapeutic measures. This report provides information on techniques for correction of contractures, atrophic scars, scars within hair-bearing regions of the face and auricular keloids. Additionally, we present adjuvant procedures in a subject-related manner.

Role of surgery in the management of head and neck cancer: a contemporary view of the data in the era of organ preservation.

OBJECTIVE: Review of the literature on the role of surgery in the management of head and neck cancer in the era of organ preservation. METHOD: Literature search based on the essential practice guidelines set out by the US National Comprehensive Cancer Network. RESULTS: Despite the increasing popularity of non-surgical treatment options, the surgeon remains a key figure in the multidisciplinary head and neck cancer team, along with the radiation oncologist, the medical oncologist and the speech and swallowing therapist. Even when organ preservation is successful, early and late toxicity may cause serious complications, including laryngeal dysfunction with a 'frozen larynx'. When organ preservation fails, salvage surgery is often associated with increased complications and reduced survival. CONCLUSION: There is a definite need to apply more rigorous standards to the use of organ preservation strategies, and to re-evaluate the role of surgery in head and neck cancer treatment.

[Orbitocutaneous fistula after orbital reconstruction]. / Orbitokutane Fistel nach Orbitarekonstruktion.

A 73-year old man presented with a lesion inferior to his left medial canthus with discharge and headache. Fifteen years previously, the patient had undergone reduction of an orbital fracture and reconstruction of the orbit with silicone. An orbitocutaneous fistula was found to originate from the implant which was displaced in the ethmoid, obstructing frontal sinus outflow. Symptoms disappeared after explantation of the implant, reconstruction of the orbit with a titanium plate and frontal sinus surgery. Although the use of silicone in facial trauma has declined, complications have to be expected even years after implantation.

[Randomized controlled trials in the surgical treatment of obstructive sleep apnea]. / Kontrollierte Studien in der operativen Therapie der obstruktiven Schlafapnoe.

The need for surgical treatment alternatives for obstructive sleep apnea is unchanged. However, recommendations regarding these treatments can often only be given with caution as there are only a limited number of controlled studies available. To perform controlled trials and even more so placebo controlled trials in the field of sleep surgery is challenging, especially in comparison to studies evaluating conservative approaches. Nevertheless, these studies can be carried out also in the field of sleep surgery. In this review we present recent concepts and high-quality surgical trials with innovative study designs. A Medline search revealed 310 studies regarding surgical treatment of sleep apnea. These studies were assessed regarding quality, execution and number of subjects. A total of 12 randomized controlled studies were identified addressing palatal implants, radio-frequency surgery, nasal surgery, maxillomandibular advancement and laser-assisted uvulopalatoplasty (LAUP). Furthermore this review addresses the limitations of surgical studies and the differences compared to trials dealing with conservative approaches. The studies presented in this review demonstrate that high-quality trials regarding surgical treatment of obstructive sleep apnea are feasible and can lead to recommendations with high evidence levels.

Complementary and alternative medications consumed by patients with head and neck carcinoma: a pilot study in Germany.

Complementary and alternative medicine (CAM) represents a wide range of treatment modalities. CAM products may interact with enzymes, transport proteins, and may therefore influence drug metabolism. The prevalence and patterns of CAM usage among patients with head and neck carcinoma (HNC) are largely unknown. This cross-sectional study was designed to document pattern of CAM consumption in patients with HNC. Statistical differences in a significantly higher prevalence of CAM consumption between tumor patients (n = 107) and the control group (n = 112) could be detected. Concerning the frequency of CAM usage, we could document a significant increased consumption of CAM among tumor patients (42.8% vs. 62.6%) especially for herbal teas (P < 0.05), phytotherapy (P < 0.001), supplement products (P < 0.05), and "other" supplements (P < 0.005) comparing the controls. Furthermore a significant influence of female gender and an increased CAM usage could be illustrated. Concerning the knowledge of potential interactions of CAM consumption, only 6.25% of the controls and 19.6% of tumor patients know about possible side effects but only 1.7% of the controls and 6.5% of the tumor patients informed their physician about the CAM usage. The frequency of CAM in head and neck tumor patients seems to be relevant in the supervision of anticancer therapies.

Palatal implants in the treatment of obstructive sleep apnea: a randomised, placebo-controlled single-centre trial.

Palatal implants have been used to treat snoring and mild to moderate obstructive sleep apnea (OSA). Two previous controlled trials have published conflicting results regarding the effects of palatal implants on objective outcome measures, although they both could demonstrate superiority over placebo. The aim of the present study was to assess the effects of palatal implants in patients with mild to moderate sleep apnea in a randomised, placebo-controlled trial. Twenty-two patients with mild to moderate OSA (AHI 18 ± 5, BMI 28 ± 3, age 51 ± 13 years) due to palatal obstruction were enrolled in this randomised, double-blind, placebo-controlled trial. Respiratory parameters and sleep efficiency (evaluated by polysomnography), snoring (evaluated by the bed partner), and daytime sleepiness (evaluated by ESS) were assessed before and 90 days after surgery. One patient in each group did not show up for follow-up. The AHI, HI and LSAT showed statistically significant improvement in the treatment group (p < 0.05). Snoring as rated by bed partners also showed statistically significant improvement within the treatment group (p = 0.025). There was no statistical difference when comparing the means of the treatment group with the placebo group. There were no peri- or post-operative complications and no extrusions during the follow-up period. The study supports the idea that palatal implants lead to a reduction in respiratory events in patients with mild to moderate OSA, although a statistically significant superiority of palatal implants over placebo could not be demonstrated in this trial.

Chemotherapeutic alteration of ß-catenin and c-kit expression by imatinib in p16-positive squamous cell carcinoma compared to HPV-negative HNSCC cells in vitro.

The most common neoplasm arising in the upper aerodigestive tract is head and neck squamous cell carcinoma (HNSCC). Tumor growth, invasion and systemic dissemination is a multistep process of dysregulated cellular signaling pathways and an altered cell-cell and cell-matrix interaction. Aberrant Wnt/ß-catenin signaling is linked to tumor development and dissemination in several tumor entities. ß-catenin is a multifunctional protein within the canonical Wnt pathway, which is an important factor for reducing cell-cell adhesion in malignant tissue and for triggering cell cycle progression and unscheduled proliferation. Another pivotal factor in carcinogenesis is the tyrosine kinase receptor c-kit, which in the case of dysregulated expression is associated with neoplastic transformation in epithelial tissue. This study evaluates the expression pattern of secreted and nuclear ß-catenin and c-kit in p16-positive and HPV-negative squamous cell carcinomas (SCC) and the vulnerability of therapy with the tyrosine kinase inhibitor imatinib as a potential targeted treatment modality compared to platinum-based chemotherapeutic drugs. The different squamous tumor cell lines were incubated with increasing concentrations of carboplatin (3 or 7.5 µmol/ml) and imatinib (18 or 30 µmol/ml). ELISA and immunohistochemical methods were carried out after 48, 72, 120, 192 and 240 h. We detected a reliable trend towards significantly decreased cytosolic and nuclear ß-catenin and c-kit expression levels in p16-positive SCC and non-HPV HNSCC cells induced by imatinib exposure for an extended incubation period, whereas platinum-based agents had no or, at best, a slight influence. Virus-transformed squamous cell carcinoma (CERV196) cells were characterized by a reduced susceptibility to an imatinib-altered ß-catenin expression. Further studies are planned to investigate this observance in HPV-positive HNSCC in vitro. The implementation of a selective molecular therapy in established chemotherapeutic regimes may enhance the efficacy of platinum-based chemotherapy without increased toxicity and could thus improve the clinical outcome in HNSCC, irrespective of the HPV status.

Ciliary function of the nose in patients with Osler`s disease and the effect of topically applied estrogens as a nose ointment.

BACKGROUND: In recent years, the positive effect of topically applied estriol nose ointment in the adjuvant therapy of Morbus-Rendu-Osler (HHT) has been proven. Due to the induced metaplasia, a complete destruction of the ciliated cells may be expected. However, data regarding the ciliary function of HHT patients with and without the use of topical estriol application are currently lacking. METHODOLOGY/PRINCIPAL: Ciliated samples were obtained by gently brushing the inferior nasal turbinate of 19 healthy volunteers and 15 patients with known HHT (8 of them regularly using 0.1% estriol nose ointment for 2 years (HHTwE) and 7 of them not using the ointment in the last 12 months (HHTwoE)). Analysis was done with an inverted phase contrast microscope connected to a high-speed digital camera. Recorded parameters were the visual integrity (VI) of the ciliary beat and its frequency (CBF) in Hz. RESULTS: The VI index of all samples showed an undisrupted, even beating pattern with a difference between the three groups. The mean CBF in all HHT patients was reduced compared to the control group`s mean CBF. Within the HHT group itself, the mean CBF was reduced in the HHTwE group compared to the HHTwoE group. CONCLUSIONS: The ciliary beat frequency of HHT patients is impaired compared to the control group and even more so if the HHT patients topically apply estriol more than 6 months. An undisrupted beating pattern is found in the HHTwE group despite the fact that estrogens induce a transformation of the ciliated columnar into a keratinizing squamous epithelium. This data may justify the adjuvant application of estriol as a nose ointment in the treatment of epistaxis in HHT patients without the fear of damage to the nose`s mucus clearance.

Nitric oxide: a promising methodological approach in airway diseases.

Nitric oxide (NO) is a potent biological mediator, and has a regulatory role in a wide variety of cellular and tissue functions. In the upper and lower airways, NO has been suggested to be involved in different functions with regulatory, protective, defensive or damaging effects. It is obvious that NO plays an important role in host defense, and is liberated in the nose and the paranasal sinuses. This review aims to highlight some aspects of the origin and function of NO in airway diseases, such as allergic rhinitis, chronic rhinosinusitis with and without nasal polyps, primary ciliary dyskinesia, and cystic fibrosis. In conclusion, NO measurement may be a promising noninvasive diagnostic marker for airway pathologies.

Chemotherapeutic alteration of VEGF-/PDGF- and PDGF-Rα/ß expression by imatinib in HPV-transformed squamous cell carcinoma compared to HPV-negative HNSCC in vitro.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy known to be the most common neoplasm appearing in the upper aerodigestive tract. The poor five-year survival rate has remained unchanged in the last decades despite the emergence of improved techniques in surgery, radiation and chemotherapy. In the last 20 years awareness of a subset of squamous cell carcinomas induced by oncogenic forms of the human papilloma virus (HPV) (high-risk types 16 and 18) has increased. The incidence of HPV-associated oropharyngeal cancer is rising, indicating the increased importance of the viral etiology. Cell proliferation, migration, induction of tumor vascularization and carcinogenesis, as well as invasion facilitation is regulated by a variety of angiogenic peptides like PDGF, PDGF-R and VEGF. They might be an encouraging target for biological anticancer therapy by inhibiting disrupted cellular signaling pathways. Imatinib has been shown to target specific tyrosine kinases, inhibiting proliferation in various cancer entities. The purpose of this study was to evaluate the expression pattern of angiogenic factors (VEGF, PDGF and PDGF-R) in HPV-positive (p16-CERV196 SCC) and (-negative squamous cell carcinoma (HNSCC). The study also evaluated the vulnerability of anti-angiogenesis therapy depending on the HPV status as potential treatment modality compared to established platinum-based chemotherapeutic drugs. The different squamous tumor cell lines were incubated with increasing concentrations of carboplatin (3 and 7.5 µmol) and imatinib (18 and 30 µmol). ELISA immunohistochemical methods were carried out after 48, 72, 120, 192 and 240 h. We demonstrated a significant reduction of VEGF and PDGF-Rα/ß expression patterns after incubation of imatinib in ELISA and immunohistochemical methods, irrespective of the HPV status of the tumor cells, whereas the application of carboplatin had no impact on the expression of angiogenic peptides. Viral oncogen-transformed squamous cell carcinoma (CERV196) cells were characterized by a reduced susceptibility for an imatinib-altered VEGF expression. Further studies are planned to investigate this observance in HPV-positive HNSCC in vitro. The implementation of a selective molecular anti-angiogenic therapy in established chemotherapeutic regimens may enhance the efficacy of platinum-based chemotherapy without an increased toxicity profile and could thus improve the clinical outcome in HNSCC, irrespective of the HPV status.

[Air conducted ocular VEMP: II. First clinical investigations]. / Luftleitungsinduzierte oculäre VEMP: II. Erste klinische Untersuchungen.

BACKGROUND: Vestibular-evoked myogenic potentials (VEMP) are widely used to assess vestibular function. Air conducted (AC) cervical VEMP (cVEMP) reflect sacculus and inferior vestibular nerve function. Ocular VEMP (oVEMP) however has been hardly examined up to now. In recent studies it has been assumed that AC oVEMP probably reflects superior vestibular nerve function. The aim of this pilot study was to evaluate clinical application of the AC oVEMP. MATERIAL AND METHODS: AC oVEMP were recorded in patients with peripheral vestibular disorders (n=21). In addition thermal irritation and head impulse test were performed and AC cVEMP were recorded. For intense AC-sound stimulation tone bursts (500 Hz) with 100 dB nHL were used. RESULTS: In peripheral vestibular disorders AC oVEMP and AC cVEMP could be classified into: • type 1 (inferior vestibular neuritis) with loss of AC oVEMP but normal AC cVEMP, • type 2, probable type of superior vestibular neuritis, showing present AC cVEMP but loss of AC oVEMP, • type 3, probable complete vestibular neuritis, without AC oVEMP and AC cVEMP. CONCLUSIONS: AC oVEMP may be used as an appropriate test for clinical investigation in patients with vestibular disorders. AC oVEMP is an additional, essential test for assessing otolith function beside AC cVEMP. Further vestibular test are necessary for precise clinical interpretation.

Synergistic effects of imatinib and carboplatin on VEGF, PDGF and PDGF-Rα/ß expression in squamous cell carcinoma of the head and neck in vitro.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. The development of new treatment modalities in order to improve long-term survival of patients with HNSCC is imperative. Numerous studies have demonstrated that carcinogenesis and tumor cell dissemination is influenced by the tumor microenvironment. The protein-kinase-receptors (PTKs) are essential elements of the intracellular signal transduction pathway and regulate cell growth, development and apoptosis. Cell proliferation, migration, induction of tumor vascularization and carcinogenesis, invasion is regulated by a variety of angiogenic factors, such as PDGF (platelet-derived growth factor), VEGF (vascular endothelial growth factor) and their respective tyrosine kinase receptors (PDGF-R and VEGF-R). They present promising targets for anti-cancer therapy through abrogation of impaired signaling pathways. Indeed, imatinib, a small molecule drug targeting these protein kinases, has antiproliferative effects in several cancer types. The purpose of this study was to investigate the potential synergism of imatinib and carboplatin on the expression of PDGF, PDGF-R α/ß and VEGF in different HNSCC cell lines. Several tumor cell lines were subjected to increasing concentrations of carboplatin (3 and 7.5 µmol/l) and imatinib (18 and 30 µmol/l) and ELISA, immunohistochemical methods and RQ-PRC after 48, 72, 120 and 240 h were used to assess their expression levels. While PDGF-Rα/ß expression was unimpaired at lower imatinib concentrations (18 µmol/l), PDGF-Rα/ß expression was suppressed at 30 µmol/l, and suppression was enhanced by the presence of carboplatin. By RQ-PCR, a significant reduction of PDGF-Rα/ß expression was detected (p<0.5). We observed explicit significant reduction in VEGF levels with increasing concentrations of imatinib and with the combination of the two chemotherapeutic drugs (p<0.5). We report for the first time evidence of synergism of imatinib and carboplatin in suppressing VEGF, PDGF and PDGF-Rα/ß expression in HNSCC.