Angela Wenzel

Detection of human utricular otoconia degeneration in vital specimen and implications for benign paroxysmal positional vertigo

Otoconia are assumed to be involved in inner ear disorders such as benign paroxysmal positional vertigo (BPPV). Up to now, the distinct structure and morphology of intact and degenerate human utricular otoconia has been only poorly investigated on vital specimen. In this study, human otoconia were obtained from the utricle in five patients undergoing translabyrinthine vestibular schwannoma surgery. Specimens were examined by environmental scanning electron microscopy. Intact and degenerate otoconia as well as fracture particles of otoconia and bone were analyzed by energy dispersive X-ray microanalysis (EDX) and powder X-ray diffraction (XRD). Intact otoconia reveal a uniform size showing characteristic symmetry properties. Degenerative changes can be observed at several stages with gradual minor and major changes in their morphology including fragment formation. EDX analyses reveal the characteristic chemical composition also for otoconia remnants. XRD shows that intact and degenerate otoconia as well as remnants consist of the calcite modification. In conclusion, electron microscopy serves as a standard method for morphological investigations of otoconia. Human utricular otoconia show a uniform outer morphology corresponding to a calcite-based nanocomposite. Morphological changes provide further evidence for degeneration of utricular otoconia in humans, which might be a preconditioning factor causing BPPV. In case of uncertain origin, particles can be clearly assigned to otoconial origin using EDX and XRD analyses.

Gentamicin-induced structural damage of human and artificial (biomimetic) otoconia

Abstract Conclusions: Gentamicin causes irreversible structural damage of human and artificial otoconia by progressive dissolution of calcite. The inner architecture of otoconia is strongly affected by degradation scenarios during gentamicin exposure. Artificial otoconia can be used as a model system mimicking the chemical attacks for detailed investigations. Objectives: To investigate the chemical interactions of gentamicin with natural calcite and human and artificial otoconia under in vivo conditions. Methods: Pure calcite crystals and artificial and human otoconia were exposed to gentamicin injection solutions at various concentrations. Morphological changes were observed in time steps by the use of environmental scanning electron microscopy (ESEM). Results: Dissolution of pure calcite crystals results in the formation of well oriented nanoshoots indicating an irreversible chemical reaction with gentamicin. Human and artificial otoconia reveal irreversible structural changes of their surface areas as well as of their inner structure, resulting in characteristic changes at different gentamicin concentrations. Minor changes are first observed by surface alterations and dissolution of calcite in the belly region. Major changes result in further reduction of the belly area reaching the center of symmetry. Finally, a complete dissolution of the branches takes place. Artificial otoconia provide detailed insight into surface alterations.

Clinical experience with video Head Impulse Test in children

BACKGROUND A standardized diagnostic protocol for childrens vestibular assessment is still missing in daily clinical life. As rotatory chair testing and caloric test are usually not tolerated well by children, the aim of our study was not only to evaluate the importance and practicability of the video head impulse test performed in children with and without balance problems, but also to outline a diagnostic algorithm for children with balance problems. METHODS Fifty-five children aged 3-16 years have been included in this prospective monocentric study. Balance was assessed using results from health screening examinations of the participants and results from a specific dizziness questionnaire for children. The children were then divided in two groups: group I without any sign of vestibular development disorder and group II with possible signs for a pathological equilibrium development. Horizontal vestibulo-ocular reflex (HVOR) was assessed using a video-oculography system device (EyeSeeCam(©)). Gain at 40, 60, and 80ms and gain variance has been measured. Furthermore, it was evaluated how calibration of the system was tolerated by the participants, how the test itself was accomplishable in children, and which difficulties arose during testing. RESULTS Reproducible test results were accomplished in 42 children (75%). Children with no balance problems in history showed a median gain of 1.02 (±0.28). A significant gain reduction between 40 and 80ms was found (P<0.05). Catch-up saccades were found in none of the children. Children with balance problems had a significantly reduced gain. (0.47±0.3; P<0.05) In this group, catch-up saccades could be detected in 4 out of 6 patients. For both groups, performing the test approximately took 20min, which is significantly longer than in adults (P<0.05). Calibration of the system with laser dots was easily doable in children aged 6 and older, whereas children between 3 and 5 years had better calibration results using colorful little icons. CONCLUSIONS Video head impulse test is a sensitive and efficient vestibular test in children, which is tolerated well by children aged 3-16 years. Therefore, video head impulse test can be easily used as a screening tool to detect vestibular dysfunction in the pediatric population.

Clinical Outcome and Quality of Life After a Multimodal Therapy Approach to Ear Keloids.

IMPORTANCE Keloids are fibroproliferative scars that can cause a huge psychological burden and severe problems for patients, such as depression. Many treatment options exist; however, recurrence rates, especially with monotherapy, remain high. OBJECTIVE To investigate the recurrence rate and changes in quality of life after multimodal therapy. DESIGN, SETTING, AND PARTICIPANTS A total of 33 patients with 42 auricle keloids (24 female and 9 male patients; mean [SD] age, 27 [17] years) were enrolled in a prospective cohort study and underwent intramarginal keloid excision and multimodal therapy. Patients were observed postoperatively in the outpatient Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital of Mannheim, from August 1, 2007, through September 30, 2014, with a mean (SD) follow-up of 30 (19) months (through August 31, 2014). A retrospective analysis of clinical outcomes was performed from September 1 through November 15, 2014. INTERVENTIONS Excision followed by 6 intralesional corticosteroid injections at 4- to 6-week intervals and individually customized pressure splints applied at least 5 nights a week for 6 months. MAIN OUTCOMES AND MEASURES Keloid recurrence rate and subjective handling of the pressure splint were evaluated during clinical visits. Quality of life was measured after the end of therapy with a 3-part questionnaire, including the Glasgow Benefit Inventory (GBI). RESULTS After excluding 4 patients (with 5 keloids) for nonadherence to treatment, 3 of 37 keloids recurred, for a recurrence rate of 8% among 29 patients. Insecure handling of the pressure splint significantly correlated with a higher relapse rate (mean subjective handling score in patients with a relapse, 3.60; P = .02). Four of 8 patients with recurrent keloids had poor adherence to adjuvant pressure therapy, which suggests an association between keloid recurrence and adherence to adjuvant pressure therapy. Patients received the 3-part questionnaire by mail to collect data on quality of life. Of 43 patients approached, 33 treated with multimodal therapy completed the questionnaire for a return rate of 77%. Improvement in quality of life after keloid treatment was significant in recurrence-free patients, with a mean GBI score of 22.53 (P < .001). CONCLUSIONS AND RELEVANCE The present study showed an improvement in quality-of-life scores after multimodal therapy for keloids. Because poor adherence to the use of ear splints correlated with a higher recurrence rate of keloids, efforts are needed to improve adherence and minimize recurrence. LEVEL OF EVIDENCE 3.

Amiodarone-associated bilateral vestibulopathy

BackgroundBilateral vestibulopathy (BVP) is a debilitating disorder characterized by the hypofunction of both vestibular end organs or nerves. The most frequent identifiable causes of BVP are ototoxic drug effects, infectious and autoimmune disorders. The majority of cases, however, remain idiopathic.MethodsMedical records of patients diagnosed with idiopathic BVP were examined in five dizziness clinics.ResultsWe identified 126 patients with “idiopathic” BVP. Out of these, 15 patients had a history of Amiodarone treatment before the diagnosis of BVP, resulting in a 12% prevalence.ConclusionThe present report supports the hypothesis that Amiodarone can cause BVP. Vestibular examination in patients taking Amiodarone and suffering from balance-related symptoms are recommended, to recognize this adverse effect as early as possible and allow for an informed judgement on a potential dose reduction or withdrawal for recovery of the vestibular function.

Lapatinib‑induced mesenchymal‑epithelial transition in squamous cell carcinoma cells correlates with unexpected alteration of β‑catenin expression

The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer progression, and may promote resistance of cancer cells to therapy. Inhibiting EMT appears to be crucial to inhibit drug resistance. The mesenchymal-epithelial transition (MET), which is the reverse program of EMT in metastases, is characterized by the upregulation of epithelial adhesive proteins such as E-cadherin, and downregulation of mesenchymal proteins such as vimentin. The sensitivity of cancer cells to epithelial growth factor receptor (EGFR) inhibitor may be increased by inducing MET in these cells. Therefore, it is of clinical importance to specify the phenotype of cancer cells in order to overcome the phenomenon of drug resistance. The aim of the present study was to investigate the expression pattern of specific markers in squamous cell carcinoma (SCC) cells following stimulation with lapatinib and gefitinib. For this purpose, the head and neck (HN) SCC cell lines HNSCC22B and HNSCC11A were incubated with 0.5 and 2 µg/ml lapatinib and gefitinib, and the levels of E-cadherin, vimentin, matrix metalloproteinase-14, c-kit and β-catenin were detected by immunocytochemistry and enzyme-linked immunosorbent assay at 5, 24 and 96 h post-incubation. The results indicated that, compared with HNSCC22B cells, the protein expression levels of vimentin increased, whereas those of E-cadherin reduced, in non-stimulated HNSCC11A cells. In addition, the protein expression levels of β-catenin were altered in the epithelial- and mesenchymal-associated SCC cell lines following treatment with lapatinib and gefitinib. Furthermore, lapatinib induced the downregulation of vimentin and upregulation of E-cadherin in HNSCC11A cells in a time-dependent manner. This suggests that the sensitivity of cancer cells to lapatinib may be improved by inducing MET in these cells. In summary, the results of the present study demonstrated that lapatinib-induced MET led to an unexpected alteration of the protein expression levels of β-catenin in SCC cells. Further studies on the mechanistic role of MET are required in order to increase the sensitivity of cancer cells to EGFR inhibitor and block the EMT process in these cells.

Superior canal dehiscence syndrome in children – A case report

Initially described in 1998, superior semicircular canal dehiscence syndrome (SCDS) has become a well-studied neurootologic entity in adults by now. Unfortunately, experience with children is limited and a diagnostic and therapeutic algorithm is lacking. The article therefore wants to provide an overview of the existing literature on superior semicircular canal dehiscence syndrome in children. Furthermore a diagnostic algorithm for daily clinical life based on a case report from an eleven-year-old girl is presented.

Isoliert hochfrequente vestibuläre Läsion bei Patienten mit chronischen Schwindelbeschwerden

In the presented study video-head impulse test (vHIT) was performed in 72 patients with complaints of dizziness for more than 3 months who did not show any pathology in rotatory chair testing or caloric test, in order to analyzed high frequency vestibular-ocular-reflex (VOR). Retrospective data analyzed of rotatory chair testing, caloric tests and vHIT results were accomplished in 72 patients. Gain, gain variance and the occurrence of catch-up saccades were measured. 10 patients (n=10; 13.8%) showed pathologic vHOR results with reduced gain. In the remaining 62 patients, a median gain of 0.85 when tested to the right respectively 0.87 when tested to the left side was assed. Especially in patients with normal results in rotatory chair testing and caloric testing, who complain of persistent dizziness and imbalance, high frequency hVOR should also be evaluated using vHIT in order to objectify and document an isolated high frequency hVOR lesion.

Long-Term Quality of Life and Nutritional Status of Patients with Head and Neck Cancer

Abstract Disease and therapy of head and neck cancer impair quality of life (QOL). QOL varies profoundly during therapy and follow-up. Aim: We sought to monitor QOL and nutritional status of patients before, during and after therapy (AT). Patients and methods: This study evaluates QOL by using the EORTC-questionnaires QLQ-C30 and H&N35, body weight and plasma albumin up to two years AT. Results: Chemoradiotherapy is the period of the most profound QOL-impairment. Postoperative QOL almost reaches preoperative levels just before adjuvant therapy and does not differ significantly from pretherapeutic QOL. Long-term QOL is not significantly deteriorated. Patients have an average weight loss of 17%. Nutritional supplements are used continuously. Xerostomia and sticky saliva are chronic symptoms that persist AT. Conclusions: QOL is an important parameter for the evaluation of therapy success. Head and neck cancer and its therapy cause permanent xerostomia, sticky saliva and need of nutritional supplements. Adequate patient information, psychooncological counseling, analgesia and nutritional support may alleviate QOL impairment.

Influence of static magnetic fields on human myoblast/mesenchymal stem cell co‑cultures

The results of surgical repair of extensive muscle tissue defects are still of primary concern, leaving patients with residual cosmetic and functional impairments. Therefore, skeletal muscle tissue engineering attempts to grow functional neo‑tissue from human stem cells to promote tissue regeneration and support defect closure. Despite intensive research efforts, the goal of stable induction of myogenic differentiation in expanded human stem cells by using clinically feasible stimuli, has not yet been reached to a sufficient extent. Therefore, the present study investigated the differentiation potential of static magnetic fields (SMFs), using co‑cultures of human satellite cells and human mesenchymal stem cells (MSCs). It has previously been demonstrated that SMFs may act as a promising myogenic stimulus. Tests were performed on co‑cultures with and without SMF exposure, using growth medium [high growth factor concentrations (GM)] and differentiation medium [low growth factors concentrations (DM)]. AlamarBlue® assay‑based cell proliferation analysis revealed no significant difference between co‑cultures with, vs. without SMF stimulation, regardless of growth factor concentrations in the cell culture medium. To determine the degree of differentiation in co‑cultures under stimulation with SMFs, semi‑quantitative gene expression measurements of the following marker genes were performed: Desmin, myogenic factor 5, myogenic differentiation antigen 1, myogenin, adult myosin heavy chain 1 and skeletal muscle α1 actin. In neither GM nor DM was a steady, significant increase in marker gene expression detected. Verifying the gene expression findings, immunohistochemical antibody staining against differentiation markers revealed that SMF exposure did not enhance myogenic maturation. Therefore, SMF treatment of human satellite cell/MSC co‑cultures did not result in the desired increase in myogenic differentiation. Further studies are required to identify a suitable stimulus for skeletal muscle tissue engineering.