Recovery of mechano-electrical transduction in rat cochlear hair bundles after postnatal destruction of the stereociliar cross-links

Mechano-electrical transduction (MET) in the stereocilia of outer hair cells (OHCs) was studied in newborn Wistar rats using scanning electron microscopy to investigate the stereociliar cross-links, Nomarski laser differential interferometry to investigate stereociliar stiffness and by testing the functionality of the MET channels by recording the entry of fluorescent dye, FM1-43, into stereocilia. Preparations were taken from rats on their day of birth (P0) or 1–4 days later (P1–P4). Hair bundles developed from the base to the apex and from the inner to outer OHC rows. MET channel responses were detected in apical coil OHCs on P1. To study the possible recovery of MET after disrupting the cross-links, the same investigations were performed after the application of Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) and allowing the treated samples to recover in culture medium for 0–20 h. We found that the structure and function were abolished by BAPTA. In P0–P1 samples, structural recovery was complete and the open probability of MET channels reached control values. In P3–P4 samples, complete recovery only occurred in OHCs of the outermost row. Although our results demonstrate an enormous recovery potential of OHCs in the postnatal period, the structural component restricts the potential for therapy in patients

Management der Primären Ciliären Dyskinesie

Die Primäre Ciliäre Dyskinesie (PCD, MIM 242650) ist eine seltene hereditäre Multisystemerkrankung mit klinisch heterogenem Phänotyp. Leitsymptom ist eine chronische Sekretretention der oberen und unteren Atemwege, welche durch die Dysfunktion motiler respiratorischer Zilien entsteht. In der Folge kommt es zur Ausbildung von Bronchiektasen, häufig zu einer Infektion durch Pseudomonas aeruginosa sowie einer abnehmenden Lungenfunktion bis hin zum Lungenversagen. Bislang gibt es kaum evidenzbasierte Therapieempfehlungen, da randomisierte Langzeitstudien zur Behandlung der PCD fehlten. In diesem Jahr wurden die Daten einer ersten placebokontrollierten Medikamentenstudie bei PCD veröffentlicht. Anlässlich dieses Meilensteins im Management der PCD wurde der vorliegende Übersichtsartikel als Konsens von Patientenvertretern sowie Klinikern, die langjährige Erfahrung in der Behandlung der PCD haben, verfasst. Diese Arbeit bietet eine Zusammenfassung aktuell eingesetzter Behandlungsverfahren, die überwiegend auf persönlichen Erfahrungen und Expertenmeinungen beruhen oder von anderen Atemwegserkrankungen wie der Cystischen Fibrose (CF), COPD oder Bronchiektasen-Erkrankung abgeleitet werden. Da es derzeit keine kurative Therapie für PCD gibt, stehen symptomatische Maßnahmen wie die regelmäßige Reinigung der Atemwege und die Behandlung von rezidivierenden Atemwegsinfektionen im Fokus. Nicht respiratorische Manifestationen werden organspezifisch behandelt. Um neben der ersten Medikamentenstudie mehr evidenzbasiertes Wissen zu generieren, werden weitere Projekte etabliert, u. a. ein internationales PCD-Register. Hierüber wird Patienten der Zugang zu klinischen und wissenschaftlichen Studien erleichtert und die Vernetzung behandelnder Zentren gefördert. Des Weiteren können Erkenntnisse über eine Genotyp-spezifische Erkrankungsschwere erlangt werden, um folglich die therapeutische Versorgung der Patienten zu verbessern und somit zu individualisieren. = Primary Ciliary Dyskinesia (PCD, MIM 242650) is a rare, hereditary multiorgan disease characterized by malfunction of motile cilia. Hallmark symptom is a chronic airway infection due to mucostasis leading to irreversible lung damage that may progress to respiratory failure. There is no cure for this genetic disease and evidence-based treatment is limited. Until recently, there were no randomized controlled trials performed in PCD, but this year, data of the first placebo-controlled trial on pharmacotherapy in PCD were published. This cornerstone in the management of PCD was decisive for reviewing currently used treatment strategies. This article is a consensus of patient representatives and clinicians, which are highly experienced in care of PCD-patients and provides an overview of the management of PCD. Treatments are mainly based on expert opinions, personal experiences, or are deduced from other lung diseases, notably cystic fibrosis (CF), COPD or bronchiectasis. Most strategies focus on routine airway clearance and treatment of recurrent respiratory tract infections. Non-respiratory symptoms are treated organ specific. To generate further evidence-based knowledge, other projects are under way, e. g. the International PCD-Registry. Participating in patient registries facilitates access to clinical and research studies and strengthens networks between centers. In addition, knowledge of genotype-specific course of the disease will offer the opportunity to further improve and individualize patient care

ICAR: endoscopic skull‐base surgery

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Pediatric radiology in oto-rhino-laryngology

Head and neck diseases in children and adolescents present special diagnostic and differential diagnostic challenges to ENT surgeons as well as to radiologists. Both disciplines have to adapt the latest radiological and interventional technologies to the needs of the pediatric patient in order to enable a minimally invasive but successful diagnostic procedure.High quality sonography by an experienced examiner is often the only imaging technique that is necessary in children and adolescents. Radiographs are rarely indicated in pediatric head and neck diseases. MRI, compared to computed tomography, has the advantage of absent radiation exposure. Additionally, due to current advances in high resolution techniques to delineate very small details or in visualization of different tissue characteristics, it has become an integral part of pre- and postoperative imaging.However, children should not be denied an adequate diagnostic procedure even if it includes sedation, intervention, or exposure to radiation. The responsible use of the diagnostic options under consideration of the therapeutic consequences is essential. It is most likely to be successful in a close interdisciplinary cooperation of pediatric ENT specialists and radiologists as well as pediatric anesthesiologists in selected cases.Although benign diseases predominate in children and adolescents, the possibility of malignancy has to be considered in cases of atypical clinical and radiological findings. In many of these young patients, the outcome and the probability of survival are directly associated with the initial diagnostic and therapeutic strategies, which should therefore be in accordance with the current guidelines of pediatric oncology therapy studies.Our collection of clinical cases consists of representative examples of useful diagnostic approaches in common and age specific diagnoses as well as in rare diseases and malformations. It shows the significance of a special knowledge in embryology and normal postnatal development for the differentiation of normal variants from pathological findings. Only in considering the results of imaging studies in their clinical context, it is possible to succeed in detecting a syndrome behind a single malformation or adequately caring for patients with a chronic disease such as cystic fibrosis