Betahistine exerts a dose-dependent effect on cochlear stria vascularis blood flow in guinea pigs in vivo

Objective: Betahistine is a histamine H1-receptor agonist and H3-receptor antagonist that is administered to treat Menière’s disease. Despite widespread use, its pharmacological mode of action has not been entirely elucidated. This study investigated the effect of betahistine on guinea pigs at dosages corresponding to clinically used doses for cochlear microcirculation. Methods: Thirty healthy Dunkin-Hartley guinea pigs were randomly assigned to five groups to receive betahistine dihydrochloride in a dose of 1,000 mg/kg b. w. (milligram per kilogram body weight), 0.100 mg/kg b. w., 0.010 mg/kg b. w., 0.001 mg/kg b. w. in NaCl 0.9% or NaCl 0.9% alone as placebo. Cochlear blood flow and mean arterial pressure were continuously monitored by intravital fluorescence microscopy and invasive blood pressure measurements 3 minutes before and 15 minutes after administration of betahistine. Results: When betahistine was administered in a dose of 1.000 mg/kg b. w. cochlear blood flow was increased to a peak value of 1.340 arbitrary units (SD: 0.246; range: 0.933–1.546 arb. units) compared to baseline (p<0.05; Two Way Repeated Measures ANOVA/Bonferroni t-test). The lowest dosage of 0.001 mg/kg b. w. betahistine or NaCl 0.9% had the same effect as placebo. Nonlinear regression revealed that there was a sigmoid correlation between increase in blood flow and dosages. Conclusions: Betahistine has a dose-dependent effect on the increase of blood flow in cochlear capillaries. The effects of the dosage range of betahistine on cochlear microcirculation corresponded well to clinically used single dosages to treat Menière’s disease. Our data suggest that the improved effects of higher doses of betahistine in the treatment of Menière’s disease might be due to a corresponding increase of cochlear blood flow

Neurotoxin injection in benign submandibular gland hypertrophy: A first choice treatment

Background Various benign clinical entities with a symptomatology of hypertrophic submandibular glands like sialadenitis, sialadenosis, sialolithiasis, or an ageing neck have been described. Botulinum toxin type A is an elegant tool in the management of these conditions. Methods This article is an original article, describing the Munich Concept of treating persistent submandibular swelling with Botulinum Toxin Type A from aesthetic and functional aspect. To shrink the affected tissue, 15 Units of Botox or Xeomin are applied in a single injection technique and under ultrasound guidance into the glands. Therefore, the 100 Units vial is being diluted with 3.5 of NaCl. Results Intraglandular injections, using a specific dilution and dosage of the neurotoxin preparations, are very effective in the management of these swellings, offering safe and long‐lasting results, with a high satisfaction rate. Our working group treated in the last 18 months 23 patients with benign, bilateral submandibular gland hypertrophies, which did not have any major complications. Conclusion As there is not yet described an ideal therapeutic strategy for the management of this symptomatology, we suggest, based on our experience, a concept with very promising results from functional and cosmetic aspect

Mediators and Cytokines in Persistent Allergic Rhinitis and Nonallergic Rhinitis with Eosinophilia Syndrome

Background: Patients with nonallergic rhinitis with eosinophilia syndrome (NARES) show typical symptoms of persistent allergic rhinitis (PAR). The aim of the present study was to compare nasal cytokine patterns between NARES and PAR. Methods: Nasal secretions of 31 patients suffering from NARES, 20 patients with PAR to house dust mite and 21 healthy controls were collected using the cotton wool method and analyzed for interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 beta (MIP-1 beta) by Bio-Plex Cytokine Assay as well as eosinophil cationic protein (ECP) and tryptase by UniCAP-FEIA. Results: NARES and PAR presented elevated levels of tryptase, while ECP was markedly increased solely in NARES compared to both the controls and PAR. Elevated levels of IL-1 beta, IL-17, IFN-gamma, TNF-alpha and MCP-1 were found in NARES compared to the controls as well as PAR. MIP-1 beta was elevated in NARES and PAR, while IL-4, IL-6 and G-CSF showed increased levels in NARES, and IL-5 was elevated in PAR only. Conclusions: In patients with NARES and PAR, eosinophils and mast cells appear to be the pivotal cells of inflammation, reflected by high levels of tryptase and ECP as well as IL-5 and GM-CSF as factors for eosinophil migration and survival. The elevated levels of proinflammatory cytokines in NARES may indicate the chronic, self-perpetuating process of inflammation in NARES which seems to be more pronounced than in PAR. IL-17 might be a factor for neutrophilic infiltration or be responsible for remodeling processes in NARES. Copyright (C) 2012 S. Karger AG, Base

De novo sensitization during subcutaneous allergen specific immunotherapy - an analysis of 51 cases of SCIT and 33 symptomatically treated controls

Since the beneficial implementation of allergen specific subcutaneous immunotherapy (SCIT), there are only a few studies on the risk of SCIT-induced neosensitizations. In 51 patients, we retrospectively analyzed sIgE and sIgG patterns by a multiplex ELISA as well as demographic and clinical features before and after SCIT. 33 allergic patients, who only received symptomatic treatment, served as controls. In 12 of 51 SCIT-treated patients (24%), we found new sIgE against allergen components of the allergen source treated by SCIT;eight of them were adults. Among controls, no adult patient showed neosensitization to components of the primarily affected allergen source. Only two children of the control group were affected by neosensitization, which was limited to major allergen components and rarely accompanied by sIgG. In the SCIT-treated group, neosensitization affected major and minor allergen components, and was accompanied by a strong induction of sIgG against major components. A clear clinical predictor of neosensitization during SCIT was not found. Comparing symptom scores, patients seem to profit more from SCIT, if neosensitization remained absent. Patients undergoing SCIT might carry an enhanced risk of neosensitization towards formerly unrecognized allergen components. According to anamnestic data, these neosensitizations might be of clinical relevance - supporting attempts towards personalized recombinant vaccines

Histaminergic H3-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow

OBJECTIVE Betahistine is a histamine-like drug that is considered beneficial in Ménière's disease by increasing cochlear blood flow. Acting as an agonist at the histamine H1-receptor and as an inverse agonist at the H3-receptor, these receptors as well as the adrenergic \textgreeka2-receptor were investigated for betahistine effects on cochlear blood flow. MATERIALS AND METHODS A total of 54 Dunkin-Hartley guinea pigs were randomly assigned to one of nine groups treated with a selection of H1-, H3- or \textgreeka2-selective agonists and antagonists together with betahistine. Cochlear blood flow and mean arterial pressure were recorded for 3 min before and 15 min after infusion. RESULTS Blockage of the H3- or \textgreeka2-receptors caused a suppression of betahistine-mediated typical changes in cochlear blood flow or blood pressure. Activation of H3-receptors caused a drop in cochlear blood flow and blood pressure. H1-receptors showed no involvement in betahistine-mediated changes of cochlear blood flow. CONCLUSION Betahistine most likely affects cochlear blood flow through histaminergic H3-heteroreceptors

Role of cancer stem cell markers ALDH1, BCL11B, BMI-1, and CD44 in the prognosis of advanced HNSCC

PURPOSE Cancer stem cells (CSCs) are held accountable for the progress of head and neck squamous cell carcinoma (HNSCC). In the presented study, the authors evaluated the prognostic value of CSC markers in two particular HNSCC cohorts. METHODS This two cohort study consisted of 85~patients with advanced stage HNSCC, treated with primary radio(chemo)therapy (pRCT), and 95~patients with HNSCC, treated with surgery and partially adjuvant radio(chemo)therapy. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were assessed. Samples were assessed for the expression of different molecular stem cell markers (ALDH1, BCL11B, BMI\hbox-1, and CD44). RESULTS In the pRCT cohort, none of the baseline patient and tumor features exhibited a~statistically significant relation with survival in either the cohort or the human papillomavirus (HPV)-stratified subcohorts. High expression of BMI\hbox-1 significantly decreased OS and DFS, while high expression of CD44 decreased all modes of survival. Multivariate analysis showed significant prognostic influence for all tested CSC markers, with high BMI\hbox-1 and CD44 decreasing survival (BMI-1: OS, DFS, DSS; CD44: OS, DFS) and high ALDH1 and BCL11B showing a~beneficial effect on survival (ALDH1: OS, DFS; BCL11B: OS, DSS). In the surgical cohort, classical prognosticators such as HPV status, R1 resection, and nodal status in HPV-negative HNSCC played a~significant role, but the tested CSC markers showed no significant effect on prognosis. CONCLUSION Although validation in independent cohorts is still needed, testing for CSC markers in patients with advanced or late stage HNSCC might be beneficial, especially if many comorbidities exist or disease is irresectable. The findings might guide the development and earlier use of targeted therapies in the future

Component resolved analysis of ash pollen allergy in Bavaria

Background: Sensitization to ash pollen is underestimated in various regions. The prevalence in Germany is about 10%. However, allergy to ash pollen is widely overlooked by allergists, since the pollination period of ash and birch in central Europe closely overlap and rhinoconjunctival symptoms during April/May are often assigned to birch pollen. Component resolved analysis of the different ash allergens is not routinely available. Therefore, we would like to question the usefulness of component resolved diagnostic via olive components, as ash and olive are both part of the Oleaceae family.Methods: 113 patients with nasal provocation and skin prick test to ash were retrospectively compared regarding their specific immunoglobulin E antibody profiles with response to native ash extract, rOle e 1, nOle e 7 and rOle e 9.Results: In nasal provocation testing 58% of 113 patients sensitized to ash were allergic, 42% were only sensitized without showing symptoms. Skin prick testing and serology against native ash extract detected most patients sensitized to ash pollen, whereas rOle e 1 was less sensitive. However, the value of measurements of skin prick test, serology to native ash extract and rOle e 1 did not allow a differentiation between an allergy and clinically silent sensitization. Specific antibodies to nOle e 7 and rOle e 9 were only seen in individual patients and were all positive for native ash extract and rOle e 1.Conclusion: Skin prick testing and serology to native extract of ash pollen are the most reliable tools to diagnose a sensitization to ash pollen for patients living in Germany. Component resolved diagnostic to the major allergen rOle e 1 as representative of the Oleaceae family is possible but was less sensitive. Diagnostic of nOle e 7 and rOle e 9 did not show any additional benefit. Regarding differentiation between allergy and clinically silent sensitization to ash pollen, provocation is the leading diagnostic tool. Concluding, in routine clinical practice the standard methodsskin prick test, serology to native ash extract and provocation testingremain crucial in the diagnosis and differentiation of ash sensitization and allergy

ToSkORL: Selbst- und Fremdeinschätzung bei der Untersuchung des Kopf-Hals-Bereichs

BACKGROUND A~central goal of medical school is acquisition of theoretical and practical competences. However, evidence on how capacity acquisition can be measured for special examination techniques is scarce. ToSkORL (Teaching of Skills in Otorhinolaryngology) is a project aimed at scientifically and didactically investigating students' self-evaluation skills in otorhinolaryngologic and head and neck examination techniques. METHODS During the examination techniques course, a~standardized oral and practical exam for nine different techniques was conducted. Using Likert scales, self-evaluation was based on questionnaires before the clinical skills exam and objective evaluation was performed by the examiners during the examination using a checklist. Self- and objective evaluation were correlated. Nine different examination skills were assessed 42~times each by a~total of 91~students. RESULTS Self-evaluation of competence in the different examination skills varied widely. Nevertheless, self- and objective evaluation correlated well overall, independent of age and gender. Students highly interested in otorhinolaryngology rated their own skills higher but tended toward overestimation. For examination items with intermediate difficulty, the highest divergences between self- and objective evaluation were found. CONCLUSION Student self-evaluations are an appropriate instrument for measuring competences in otorhinolaryngologic examinations. Instructors should focus on items with allegedly intermediate difficulty, which are most often over- and underestimated. ZUSAMMENFASSUNG HINTERGRUND: Ein zentrales Ziel des Medizinstudiums ist der Erwerb theoretischer und praktischer Kompetenzen. Es mangelt jedoch an Evidenz, wie der Erwerb von Kompetenzen in speziellen Untersuchungstechniken gemessen werden kann. ToSkORL (Teaching of Skills in Otorhinolaryngology) ist ein Projekt, das die studentische Selbstwahrnehmung ihrer Kompetenz bei speziellen Untersuchungstechniken der Hals-Nasen-Ohren-Heilkunde und des Kopf-Hals-Bereichs aus didaktisch-wissenschaftlicher Sichtweise beleuchtet. METHODIK Im Rahmen des Untersuchungskurses erfolgte eine standardisierte mündlich-praktische Prüfung zu neun verschiedenen Untersuchungstechniken. Vor der Prüfung erfolgte eine Evaluation der studentischen Selbsteinschätzung mittels Fragebogen, die Prüfung wurde mittels Checkliste durch die Prüfenden standardisiert geprüft. Selbst- und Fremdeinschätzung nach der Likert-Skala wurden korreliert. Die neun Untersuchungstechniken wurden jeweils 42-mal von insgesamt 91~Studierenden in gegenseitiger Untersuchung durchgeführt. ERGEBNISSE Die Selbsteinschätzung der Kompetenz in den Untersuchungstechniken variiert erheblich, insgesamt schätzten Studierende ihre eigene Untersuchungskompetenz weitgehend unabhängig von Alter und Geschlecht meist realistisch ein. Studierende mit einem hohen Interesse an der Hals-Nasen-Ohren-Heilkunde gaben bessere Selbsteinschätzungen an, neigten jedoch auch eher zur Selbstüberschätzung. Bei Untersuchungen des mittleren Schwierigkeitsniveaus ergab sich die größte Divergenz von Selbst- und Fremdeinschätzung. SCHLUSSFOLGERUNG Die studentische Selbsteinschätzung ist ein geeignetes Instrument zur Messung der Untersuchungskompetenz in der Hals-Nasen-Ohren-Heilkunde. Es sollte ein besonderer Fokus auf die Lehre vermeintlich mittelschwerer Untersuchungstechniken gelegt werden, da diese am stärksten über- und unterschätzt werden