Christoph Klingmann

Transsynaptic delivery of nanoparticles to the central auditory nervous system

Conclusion. Silica nanoparticles may serve as a nonviral delivery system to the sensory hair cells, spiral ganglion cells within the cochlea, and the vestibular organ, as well as the cochlear nucleus. Objectives. At present there are no targeted therapeutics for inner ear disease. A variety of viral vector systems have been tested in the inner ear with variable efficacy but they are still not regarded as safe systems for inner ear delivery. Nanoparticles are a nonviral method of delivering a variety of macromolecules that potentially can be used for delivery within the auditory system. In this study, we evaluated the distribution and safety of nanoparticles in the inner ear. Materials and methods. Cy3-labeled silica nanoparticles were placed on the round window membrane of adult mice. Hearing thresholds were determined after nanoparticle delivery by auditory brainstem responses (ABRs). Distribution of particles was determined by histological evaluation of the cochlea, vestibular organs, and brain stem. Results. Fluorescent microscopy demonstrated Cy3-labeled nanoparticles signals in the sensory hair cells and the spiral ganglion neurons of both the treated and contralateral inner ears. Additionally, the distal part of the central auditory pathway (dorsal cochlear nucleus, superior olivary complex) was found to be labeled with the Cy3-linked silica nanoparticles, indicating a retrograde axonal transport. No hearing loss or inflammation was noted in the treated cochlea.

Embolic Inner Ear Decompression Illness: Correlation With a Right-to-Left Shunt†

Objectives/Hypothesis Inner ear decompression illness is thought to be a rare phenomenon in recreational divers, isolated signs and symptoms of inner ear dysfunction usually being attributed to inner ear barotrauma.

Barotrauma and decompression illness of the inner ear: 46 cases during treatment and follow-up.

Introduction: Diving accidents affecting the inner ear are much more common than was once thought. Among the 319 patients treated in our clinic between January 2002 and November 2005, 46 cases involved 44 divers with symptoms of acute inner ear disorders. The objective of the present article is to investigate the symptoms of the acute disorders and assess any residual damage. Study Design: Retrospective case analysis. Materials and Methods: The medical records were used to study the cases of 18 divers treated for inner ear decompression illness on 20 occasions and 26 divers who had inner ear barotrauma. The symptoms of the disorder at the beginning of treatment, latency period before the first therapeutic measures, kind of initial therapy, symptoms after the accident, and hearing and balance functions at the last examination in our clinic were assessed. Divers with inner ear decompression illness were examined via means of transcranial or carotid Doppler ultrasonography for the presence of a vascular right-to-left (R/L) shunt. Results: Of 18 divers with inner ear decompression illness, 17 reported vertigo as the main symptom. In one diver, the inner ear decompression illness was manifested bilaterally. The divers with inner ear decompression illness had been treated with hyperbaric oxygen therapy in 14 of 20 cases; the average latency period before the start of therapy was 40 hours (median, 10 h). In 15 (83%) of 18 patients, a large R/L shunt was detected, and in 14 (78%) of 18 patients, residual cochleovestibular damage was detected. Only 9 of 26 patients with inner ear barotrauma mentioned feeling dizzy, and in no patient was vertigo the main symptom. Twenty-one patients complained of tinnitus, whereas 20 complained of hearing loss. The hearing loss ranged from an unobtrusive difference of 10 dB between the ears up to complete deafness. Three patients were subjected to tympanoscopy because of suspected rupture of the round window membrane. Of patients with inner ear barotrauma, 78% had residual cochleovestibular damage. Conclusion: We describe for the first time a patient with bilateral manifestation of inner ear decompression illness. Inner ear decompression illness is frequently associated with a R/L shunt; therefore, after a diving accident, the patients fitness to dive should be assessed via a specialist in diving medicine. Both decompression illness and barotrauma of the inner ear result in residual cochleovestibular damage in more than three of four patients.

Otorhinolaryngologic disorders and diving accidents: an analysis of 306 divers.

Diving is a very popular leasure activity with an increasing number of participants. As more than 80% of the diving related problems involve the head and neck region, every otorhinolaryngologist should be familiar with diving medical standards. We here present an analysis of more than 300 patients we have treated in the past four years. Between January 2002 and October 2005, 306 patients presented in our department with otorhinological disorders after diving, or after diving accidents. We collected the following data: name, sex, age, date of treatment, date of accident, diagnosis, special aspects of the diagnosis, number of dives, diving certification, whether and which surgery had been performed, history of acute diving accidents or follow up treatment, assessment of fitness to dive and special remarks. The study setting was a retrospective cohort study. The distribution of the disorders was as follows: 24 divers (8%) with external ear disorders, 140 divers (46%) with middle ear disorders, 56 divers (18%) with inner ear disorders, 53 divers (17%) with disorders of the nose and sinuses, 24 divers (8%) with decompression illness (DCI) and 9 divers (3%) who complained of various symptoms. Only 18% of the divers presented with acute disorders. The most common disorder (24%) was Eustachian tube dysfunction. Female divers were significantly more often affected. Chronic sinusitis was found to be associated with a significantly higher number of performed dives. Conservative treatment failed in 30% of the patients but sinus surgery relieved symptoms in all patients of this group. The middle ear is the main problem area for divers. Middle ear ventilation problems due to Eustachian tube dysfunction can be treated conservatively with excellent results whereas pathology of the tympanic membrane and ossicular chain often require surgery. More than four out of five patients visited our department to re-establish their fitness to dive. Although the treatment of acute diving-related disorders is an important field for the treatment of divers, the main need of divers seems to be assessment and recovery of their fitness to dive.

Assessment of genotoxic effects and changes in gene expression in humans exposed to formaldehyde by inhalation under controlled conditions

Forty-one volunteers (male non-smokers) were exposed to formaldehyde (FA) vapours for 4 h/day over a period of five working days under strictly controlled conditions. For each exposure day, different exposure concentrations were used in a random order ranging from 0 up to 0.7 p.p.m. At concentrations of 0.3 and 0.4 p.p.m., four peaks of 0.6 or 0.8 p.p.m. for 15 min each were applied. During exposure, subjects had to perform bicycle exercises (∼80 W) four times for 15 min. Blood samples, exfoliated nasal mucosa cells and nasal biopsies were taken before the first and after the last exposure. Nasal epithelial cells were additionally sampled 1, 2 and 3 weeks after the end of the exposure period. The alkaline comet assay, the sister chromatid exchange test and the cytokinesis-block micronucleus test were performed with blood samples. The micronucleus test was also performed with exfoliated nasal mucosa cells. The expression (mRNA level) of the glutathione (GSH)-dependent formaldehyde dehydrogenase (FDH, identical to alcohol dehydrogenase 5; ADH5; EC 1.2.1.46) was measured in blood samples by quantitative real-time reverse transcription-polymerase chain reaction with TaqMan probes. DNA microarray analyses using a full-genome human microarray were performed on blood samples and nasal biopsies of selected subgroups with the highest FA exposure at different days. Under the experimental conditions of this study, inhalation of FA did not lead to genotoxic effects in peripheral blood cells and nasal mucosa and had no effect on the expression of the FDH gene. Inhalation of FA did also not cause alterations in the expression of genes in a microarray analysis with nasal biopsies and peripheral blood cells.

Decompression illness reported in a survey of 429 recreational divers

BACKGROUND The purpose of this study was to investigate the influence of diving experience and diving techniques on the lifetime incidence of decompression illness (DCI). METHODS Attendants of three diving medical symposia voluntarily answered a questionnaire about their age, gender, medical history, diving experience, diving habits, diving certification levels, and diving associated incidents (cross-sectional survey). RESULTS Out of 650 divers, 429 completed the questionnaire. The study population consisted of experienced divers with an average of 670 dives. The majority of the divers were certified diving instructors (43%). There were 37 participants (8.7%) who were classified as technical divers with an average of 1193 logged dives. There was an overall lifetime incidence of DCI of 1 per 5463 dives. The complete study group showed an increased lifetime incidence of DCI with decreased diving experience (1.97-fold to 8.17-fold higher). Of the divers, 27% reported severe DCI with neurological symptoms. The lifetime incidence for severe DCI was 1 in 20,291 dives. Again, lifetime incidence for severe DCI was increased with decreased diving certification level (1.1-fold to 13.7-fold higher). Technical divers showed a DCI lifetime incidence of 1 to 8591 dives compared to the non-technical divers with a lifetime incidence of 1 to 5077 dives (not significant). CONCLUSION In our study population, the lifetime incidence of DCI was increased in divers with less diving experience. If further studies confirm this finding, diving federations should be encouraged to intensify their efforts of educating divers and should limit diving time and depth in inexperienced divers.

Entwicklung und Validierung des Parotidectomy Outcome Inventory 8 (POI-8)

ZusammenfassungHintergrundBisher stand kein validiertes Instrument zur Messung der Lebensqualität nach Parotidektomie bei benignen Erkrankungen der Parotis zur Verfügung.Material und MethodenIn diese retrospektive Studie wurden Patienten eingeschlossen, die sich in den Jahren 2003 bis 2006 einer Parotidektomie aufgrund einer benignen Erkrankung unterzogen. Eine Expertengruppe identifizierte Einzelfragen, die potenzielle Beschwerden nach einer Parotidektomie erfassten (alpha-Version). Nach Ausfüllen des Fragebogens durch die Patienten erfolgte eine Itemreduktion durch sequenzielle statistische Analyseverfahren. Die daraus resultierende beta-Version wurde validiert durch Bestimmung der Reliabilität und der Validität.ErgebnisseIn die Studie wurden 199 Patienten eingeschlossen, von denen 70 (35%) die Fragebögen ausfüllten. Die alpha-Version des Instruments wies 20 Items auf (Parotidectomy Outcome Inventory-20, POI-20), die beta-Version 8 Items (POI-8). Das Cronbach-alpha wies mit einem Wert von 0,84 auf eine gute interne Konsistenz hin. Die Messung der Test-Retest-Reliabilität des POI-8 bei 49 Patienten zeigte eine hochsignifikante Korrelation (r=0,91). Das Bestehen einer guten Übereinstimmungsvalidität mit einer globalen krankheitsspezifischen Frage konnte gezeigt werden (r=0,78).SchlussfolgerungenDer POI-8 ist das erste krankheitsspezifische reliable und valide Instrument zur Messung der gesundheitsbezogenen Lebensqualität nach Parotidektomie bei benignen Erkrankungen der Ohrspeicheldrüse.AbstractBackgroundTo date, no validated instrument for measuring health-related quality of life (QOL) in patients after parotidectomy for benign disease has been available.MethodsIn our retrospective study we included patients who had undergone parotidectomy for benign disease between 2003 and 2006. A group of experts identified single items with a potential impact on postoperative complaints (alpha version). After the patients had filled out the questionnaire item reduction was performed by sequential statistical analysis. The beta version of the instrument resulting from this procedure was then validated by the evaluation of reliability and validity.ResultsWe included 199 patients in the study, of which 70 (35%) returned the completed questionnaires. The alpha version of the instrument contained 20 items (Parotidectomy Outcome Inventory-20, POI-20), while the beta version consisted of 8 items (POI-8). Cronbach’s alpha was 0.84, indicating good internal consistency. The test-retest reliability score for POI-8 in 49 patients was highly correlated (r=0.91). Furthermore, we found a good concurrent validity with a global disease specific question (r=0.78).ConclusionsThe POI-8 is the first reliable and valid instrument for measuring health-related QOL in patients after parotidectomy for benign disease.BACKGROUND To date, no validated instrument for measuring health-related quality of life (QOL) in patients after parotidectomy for benign disease has been available. METHODS In our retrospective study we included patients who had undergone parotidectomy for benign disease between 2003 and 2006. A group of experts identified single items with a potential impact on postoperative complaints (alpha version). After the patients had filled out the questionnaire item reduction was performed by sequential statistical analysis. The beta version of the instrument resulting from this procedure was then validated by the evaluation of reliability and validity. RESULTS We included 199 patients in the study, of which 70 (35%) returned the completed questionnaires. The alpha version of the instrument contained 20 items (Parotidectomy Outcome Inventory-20, POI-20), while the beta version consisted of 8 items (POI-8). Cronbachs alpha was 0.84, indicating good internal consistency. The test-retest reliability score for POI-8 in 49 patients was highly correlated (r=0.91). Furthermore, we found a good concurrent validity with a global disease specific question (r=0.78). CONCLUSIONS The POI-8 is the first reliable and valid instrument for measuring health-related QOL in patients after parotidectomy for benign disease.

Development and validation of the Tonsillectomy Outcome Inventory 14

BACKGROUND Until now, no validated instrument to measure disease-specific, health-related quality of life (HR-QOL) in adults with chronic tonsillitis (CTO) exists. MATERIAL AND METHODS After an item reduction of the alpha-version of the Tonsillectomy Outcome Inventory (TOI), the TOI-14 resulted. In addition to the total score, it includes the subscales throat problems, overall health, resources, and social-psychological restrictions. In phase 2, the TOI-14 was prospectively validated on 108 adults with CTO, who had undergone a tonsillectomy. RESULTS The TOI-14 had, on average, good reliability. It included all important aspects of the HR-QOL. Patients with CTO can be distinguished with high sensitivity from healthy subjects. All scores showed moderate to good correlation with the subjective limitation in quality of life. The sensitivity of the questionnaire demonstrated major effects postoperatively. CONCLUSION The TOI-14 constitutes the first worldwide-validated, disease-specific instrument to measure HR-QOL in adults with CTO. Due to its ease of use, it can be utilized both in the outcome research and in clinical routine.

Chronic rhinosinusitis. Subjective assessment of benefit 1 year after functional endonasal sinus surgery

ZusammenfassungHintergrundVor dem Hintergrund eines ständig wachsenden Kostendrucks im Gesundheitswesen wird der Nachweis des subjektiven und ökonomischen Nutzens verschiedener Therapieformen in Zukunft eine Voraussetzung für die Leistungserstattung durch die Kostenträger sein. Das Ziel der vorliegenden Studie ist es, diesen Nachweis für die funktionelle endonasale Nasennebenhöhlenoperation (FESS) bei Patienten mit chronischer Rhinosinusitis (CRS) zu erbringen.Patienten und MethodenEin Jahr nach einer FESS aufgrund einer CRS wurden 82 Patienten befragt. Als validiertes Messinstrument zur Nutzenbewertung wurde der Glasgow Benefit Inventory (GBI) eingesetzt. Zusätzlich wurden die Patienten bezüglich der prä- und postoperativen Ressourcennutzung (Antibiotikaeinnahme, Arztbesuche, Zeiten der Arbeitsunfähigkeit) befragt und aufgefordert, eine globale Einschätzung ihrer Zufriedenheit mit dem Ergebnis, der Änderung der Beschwerden und der potentiellen Weiterempfehlung dieser Therapie abzugeben.ErgebnisseIn drei von vier Skalen des GBI [Gesamtnutzen (+22,6), allgemeiner Nutzen (+26,8), körperliche Gesundheit (+23,7)] wurden eindeutig positive Nutzenbewertungen abgegeben. Die Häufigkeit der Arztbesuche und der Einnahme von Antibiotika sowie von Zeiten der Arbeitsunfähigkeit wurde signifikant reduziert. Die Patienten waren weit überwiegend zufrieden mit dem Gesamtergebnis und der Beschwerdeänderung und würden die FESS an Freunde etc. weiterempfehlen.SchlussfolgerungenDie FESS wurde von Patienten mit CRS subjektiv überwiegend als sehr nutzbringend eingeschätzt und führte zu einer deutlichen Reduzierung der Ressourcennutzung.AbstractBackgroundAgainst the background of constantly intensifying economic pressure in the healthcare sector, in the future confirmation of subjective and economic benefit of different forms of therapy will be the criterion applied by the health insurance companies to decide whether to reimburse the costs they involve. The aim of this study was to provide confirmation that patients with chronic rhinosinusitis (CRS) do benefit from functional endonasal sinus surgery (FESS).Patients and methodsOne year after undergoing FESS for the treatment of CRS, 82 patients completed various questionnaires. The Glasgow Benefit Inventory (GBI) was used, as it is a validated instrument for the assessment of benefit. In addition, the patients were asked to complete questionnaires relating to pre- and postoperative use of resources (use of antibiotics, visits to their doctors and time unfit for work) and also to give an overall rating of their satisfaction with the outcome, the difference in their symptoms after FESS and the likelihood that they would recommend this treatment to friends or relatives.ResultsThree out of four GBI scales [total score (+22.6), general benefit (+26.8), physical functioning (+23.7)] indicated that patients experienced significant benefit. The frequency of visiting their doctors, their intake of antibiotics and the amount of time off work were all significantly reduced. The vast majority of patients were satisfied with the overall result and the level of symptom relief achieved and would recommend FESS to friends and relatives.ConclusionThe vast majority of these patients with CRS experienced FESS as highly beneficial. A significant reduction of resource usage was reported after the operation.

[Development and validation of the Parotidectomy Outcome Inventory 8 (POI-8). Measurement of quality of life after parotidectomy in benign diseases].

ZusammenfassungHintergrundBisher stand kein validiertes Instrument zur Messung der Lebensqualität nach Parotidektomie bei benignen Erkrankungen der Parotis zur Verfügung.Material und MethodenIn diese retrospektive Studie wurden Patienten eingeschlossen, die sich in den Jahren 2003 bis 2006 einer Parotidektomie aufgrund einer benignen Erkrankung unterzogen. Eine Expertengruppe identifizierte Einzelfragen, die potenzielle Beschwerden nach einer Parotidektomie erfassten (alpha-Version). Nach Ausfüllen des Fragebogens durch die Patienten erfolgte eine Itemreduktion durch sequenzielle statistische Analyseverfahren. Die daraus resultierende beta-Version wurde validiert durch Bestimmung der Reliabilität und der Validität.ErgebnisseIn die Studie wurden 199 Patienten eingeschlossen, von denen 70 (35%) die Fragebögen ausfüllten. Die alpha-Version des Instruments wies 20 Items auf (Parotidectomy Outcome Inventory-20, POI-20), die beta-Version 8 Items (POI-8). Das Cronbach-alpha wies mit einem Wert von 0,84 auf eine gute interne Konsistenz hin. Die Messung der Test-Retest-Reliabilität des POI-8 bei 49 Patienten zeigte eine hochsignifikante Korrelation (r=0,91). Das Bestehen einer guten Übereinstimmungsvalidität mit einer globalen krankheitsspezifischen Frage konnte gezeigt werden (r=0,78).SchlussfolgerungenDer POI-8 ist das erste krankheitsspezifische reliable und valide Instrument zur Messung der gesundheitsbezogenen Lebensqualität nach Parotidektomie bei benignen Erkrankungen der Ohrspeicheldrüse.AbstractBackgroundTo date, no validated instrument for measuring health-related quality of life (QOL) in patients after parotidectomy for benign disease has been available.MethodsIn our retrospective study we included patients who had undergone parotidectomy for benign disease between 2003 and 2006. A group of experts identified single items with a potential impact on postoperative complaints (alpha version). After the patients had filled out the questionnaire item reduction was performed by sequential statistical analysis. The beta version of the instrument resulting from this procedure was then validated by the evaluation of reliability and validity.ResultsWe included 199 patients in the study, of which 70 (35%) returned the completed questionnaires. The alpha version of the instrument contained 20 items (Parotidectomy Outcome Inventory-20, POI-20), while the beta version consisted of 8 items (POI-8). Cronbach’s alpha was 0.84, indicating good internal consistency. The test-retest reliability score for POI-8 in 49 patients was highly correlated (r=0.91). Furthermore, we found a good concurrent validity with a global disease specific question (r=0.78).ConclusionsThe POI-8 is the first reliable and valid instrument for measuring health-related QOL in patients after parotidectomy for benign disease.BACKGROUND To date, no validated instrument for measuring health-related quality of life (QOL) in patients after parotidectomy for benign disease has been available. METHODS In our retrospective study we included patients who had undergone parotidectomy for benign disease between 2003 and 2006. A group of experts identified single items with a potential impact on postoperative complaints (alpha version). After the patients had filled out the questionnaire item reduction was performed by sequential statistical analysis. The beta version of the instrument resulting from this procedure was then validated by the evaluation of reliability and validity. RESULTS We included 199 patients in the study, of which 70 (35%) returned the completed questionnaires. The alpha version of the instrument contained 20 items (Parotidectomy Outcome Inventory-20, POI-20), while the beta version consisted of 8 items (POI-8). Cronbachs alpha was 0.84, indicating good internal consistency. The test-retest reliability score for POI-8 in 49 patients was highly correlated (r=0.91). Furthermore, we found a good concurrent validity with a global disease specific question (r=0.78). CONCLUSIONS The POI-8 is the first reliable and valid instrument for measuring health-related QOL in patients after parotidectomy for benign disease.