0000000000161911
AUTHOR
Kai Helling
Low-Frequency Therapeutic Ultrasound with Varied Duty Cycle: Effects on the Ischemic Brain and the Inner Ear
Sonothrombolysis is a promising modality for acute stroke treatment. In vitro data suggest a duty cycle dependence of sonothrombolytic efficacy of low-frequency applications. The aim of our study was to examine its impact on safety issues in a rat model of middle cerebral artery occlusion. Rats were exposed to transcranial 60-kHz ultrasound with varied duty cycles. To determine effects on the inner ear, the acoustic threshold was determined in additional healthy animals (acoustic evoked potentials). A short duty cycle (20%) resulted in significant adverse effects (ischemic volume, hemorrhage, functional outcome), which was not observed in longer duty cycle (80%). Continuous-wave insonation …
Treatment of Ménière's disease by low-dosage intratympanic gentamicin application: effect on otolith function.
Objectives: The intratympanic application of a low dosage of gentamicin is increasingly favored as treatment for Meniere's disease. While posttreatment observations have confirmed a long-term success of the therapy of vertigo attacks, clear differences in the posttreatment recovery interval can be observed. In addition to differences in central-vestibular compensation, the degree of peripheral vestibular damage, i.e., to the saccule, utricle, and semicircular canal ampullae, varies among patients. This study provides comprehensive pre- and posttreatment results from unilateral functional tests of the individual vestibular receptors and of the cochlea in patients with Meniere's disease. Stud…
Ascorbic acid reduces noise-induced nitric oxide production in the guinea pig ear.
Objectives: Noise-induced hearing loss can be caused, among other causes, by increased nitric oxide (NO) production in the inner ear leading to nitroactive stress and cell destruction. Some studies in the literature suggest that the degree of hearing loss (HL) could be reduced in an animal model through ascorbic acid supplementation. To identify the effect of ascorbic acid on tissue-dependent NO content in the inner ear of the guinea pig, we determined the local NO production in the organ of Corti and the lateral wall separately 6 hours after noise exposure. Study Design: Prospective animal study in guinea pigs. Methods: Over a period of 7 days, male guinea pigs were supplied with minimum (…
Gentamicin alters Akt-expression and its activation in the guinea pig cochlea
Gentamicin treatment induces hair cell death or survival in the inner ear. Besides the well-known toxic effects, the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway was found to be involved in cell protection. After gentamicin application, the spatiotemporal expression patterns of Akt and its activated form (p-Akt) were determined in male guinea pigs. A single dose of 0.1 mL gentamicin (4 mg/ear/animal) was intratympanically injected. The auditory brainstem responses (ABRs) were recorded prior to application and 1, 2 and 7 days afterward. At these three time points the cochleae (n=10 in each case) were removed, transferred to fixative and embedded in paraffin. Seven ears were used as u…
Comparison of electronystagmography results with dynamic posturography findings in patients with vestibular schwannoma.
Condition-5-score (C5S) and condition-6-score (C6S) of computerized dynamic platform posturography (CDPP) can detect the presence of a functional deficit of the lateral semicircular canal (and the superior vestibular nerve), irrespective of the central vestibular compensatory status, in vestibular schwannoma (VS) patients.To test whether CDPP findings differ between VS patients with and without asymmetry on caloric and/or rotational ENG studies.This was a retrospective review of 216 consecutive patients with VS. C5S and C6S of CDPP (Equitest) were compared among patients with normal caloric and rotational studies, patients with asymmetry on caloric studies and normal rotational studies, and…
Dexamethasone prevents hearing loss by restoring glucocorticoid receptor expression in the guinea pig cochlea
Objectives/Hypothesis Dexamethasone is widely used in the treatment of various inner ear diseases. However, knowledge about its direct impact on glucocorticoid receptor (GR) expression is still limited. Study Design Prospective animal study in male guinea pigs. Methods A therapeutic concentration of dexamethasone (8mg/mL) or a physiological concentration of NaCl (0.9% solution) were intratympanically injected into the ears of guinea pigs (n = 10 in each case) 14 hours prior to 90 dB noise exposure (1 hour). Eighteen ears were exposed to noise only. Seven untreated ears were used as controls. Auditory brainstem responses were recorded prior to noise exposure or treatment and 2 hours thereaft…
Die Utrikulusläsion—isoliertes Krankheitsbild und Begleiterkrankung
Bis vor wenigen Jahren beschrankte sich die Funktionsprufung des peripher-vestibularen Labyrinths auf die Untersuchung der Bogengange, so dass im Allgemeinen bei normaler kalorischer Prufung und ausgewogener Drehpendelprufung von einer regelrechten peripher-vestibularen Funktion gesprochen wurde. Zwei wesentliche Grunde haben zu dieser vereinfachten und teilweise falschen Betrachtung beigetragen. Zum einen ist in vielen Fallen das klinische Bild der periphervestibularen Erkrankung von der Akutsymptomatik des lateralen Bogengangs dominiert, wie etwa bei der Neuropathia vestibularis oder beim akuten Schub eines M. Meniere. In diesen Fallen ist die Untersuchung des vestibulo-okularen Reflexes …
Evidence of unilateral isolated utricular hypofunction
The findings demonstrate that an enduring unilateral utricular dysfunction, possibly together with canal hypofunction, can occur after labyrinthine disease or injury. They also suggest that unilateral, isolated utricular dysfunction - or utricle paresis - can occur, representing a novel entity in the differential diagnosis of peripheral vestibular function. The occurrence of subjective visual vertical (SVV) asymmetry in the presence of symmetric vestibular evoked myogenic potentials (VEMPs) also confirms that the information from the utricles, rather than the saccules, dominates SVV estimation.To determine the incidence of unilateral utricular hypofunction.The retrospective clinical study d…
Gentamicin alters nitric oxide production in semicircular canals and otolith organs.
Objectives/Hypothesis: Intratympanic application of gentamicin is an important therapeutic option to control vertigo spells in Meniere's disease. Low doses eliminate the function of semicircular canal ampullae (SCCA) and saccule in most patients, although utricular function is maintained in many cases. Local alteration in free radical production might be responsible for these differences. Therefore, the gentamicin-induced nitric oxide (NO) production was determined in an animal model using separate organ cultures of SCCA, saccule, and utricle. Study Design: Prospective pilot study in male guinea pigs. Methods: SCCA, saccule, and utricle of 28 guinea pigs were isolated and incubated separate…
Localization of Congenital Tegmen Tympani Defects
Objective: This study sets out to demonstrate the normal developmental steps of the tegmen tympani and thus explains the typical localization of congenital tegmental defects. Specimens: For this study, 79 macerated and formalin-fixed human temporal bones from 14th fetal week to adults were observed and prepared. Intervention: Macroscopic and microscopic examination of the prenatal and postnatal changes of the tegmen tympani during its development. Main Outcome Measure: Temporal bones from 14th fetal week to adults underwent descriptive anatomic studies to understand the normal development of the tegmen tympani and to find a possible cause of its congenital defects. Results: The medial part …
17β-Estradiol Reduces Nitric Oxide Production in the Guinea Pig Cochlea
Intense noise exposure and the application of ototoxic substances result in increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO). In order to reduce the free NO concentration in the inner ear under pathological conditions, the use of natural cytoprotective substances such as 17β-estradiol is a promising therapeutic concept. In male guinea pigs the organ of Corti and the lateral wall were isolated from the cochlea and afterwards incubated for 6 h in cell-culture medium. 17β-Estradiol was adjusted in 2 concentrations to organ cultures of the right ears (12 animals per concentration). The left ears were used as controls. The NO produc…
Cell-specific accumulation patterns of gentamicin in the guinea pig cochlea.
Intratympanic gentamicin therapy has become a popular treatment modality for Meniere's disease (MD) through controlled elimination of vertigo spells caused by the balance organ. However, the known ototoxic properties of aminoglycosides lead to cochlear damage. In order to gain more information about cellular preferences for aminoglycoside accumulation within the cochlea, gentamicin was immuno histochemically localized by light microscopy in male guinea pigs 1 and 7 days after intratympanic application (n = 8 ears/incubation time). Differences in the gentamicin-specific cellular storage capacities were quantified by determination of the local immuno staining intensities. Gentamicin was detec…
Nitric oxide--a versatile key player in cochlear function and hearing disorders.
Nitric oxide (NO) is a signaling molecule which can generally be formed by three nitric oxide synthases (NOS). Two of them, the endothelial nitric oxide synthase (eNOS) and the neural nitric oxide synthase (nNOS), are calcium/calmodulin-dependent and constitutively expressed in many cell types. Both isoforms are found in the vertebrate cochlea. The inducible nitric oxide synthase (iNOS) is independent of calcium and normally not detectable in the un-stimulated cochlea. In the inner ear, as in other tissues, NO was identified as a multitask molecule involved in various processes such as neurotransmission and neuromodulation. In addition, increasing evidence demonstrates that the NO-dependent…
Doxycycline reduces nitric oxide production in guinea pig inner ears.
Abstract Objective Gentamicin application is an important therapeutic option to control vertigo spells in Meniere's disease. However, even in the case of low-dose intratympanic application, gentamicin might contribute to a pathological NO-increase leading to cochlear damage and hearing impairment. The study was performed to evaluate the nitric oxide (NO) reducing capacity of doxycycline in the inner ear after NO-induction by gentamicin. Methods In a prospective animal study, a single dose of gentamicin (10 mg/kg body weight) was injected intratympanically into male guinea pigs (n = 48). The auditory brainstem responses (ABRs) were recorded prior to application and 3, 5 and 7 days afterwards…
Testing utricular function by means of on-axis rotation
Subjective visual vertical (SVV) estimation during on-axis rotation provides an efficient screening test of utricle function. The survey demonstrates that isolated disorders of peripheral utricular function can occur while SCC function appears normal.The present study aimed to investigate estimation of SVV during constant velocity yaw rotation (with the head held on-axis--to enhance any asymmetry between right and left utricular responses), as a useful screening test.In all, 230 patients were recruited from the dizziness clinic. For each patient, the SVV was estimated (a) while held stationary, and (b) during constant angular velocity (240 degrees/s), with the head centred on-axis. Bitherma…
Malignant paraganglioma caused by a novel germline mutation of the succinate dehydrogenase D-gene--a case report.
Background Paragangliomas of the head and neck are rare, mostly benign tumors. Approximately 10% to 15% of paragangliomas are caused by mutations in the succinate dehydrogenase (SDH) genes B, C, or D. These are often multifocal as part of paraganglioma syndromes and hormone secreting, and malignant particularly associated with mutations in SDHB. Methods and Results A 29-year-old man was seen with recurrent paraganglioma. The patient's father reportedly suffered from bilateral carotid body tumors. Imaging studies showed metastases in both lungs and the liver. There was no increased hormone production by the tumor. Sequence analysis of the SDH genes revealed a novel C to T nonsense mutation i…
Gentamicin increases nitric oxide production and induces hearing loss in guinea pigs.
Objectives/Hypothesis: Gentamicin application is an important therapeutic option for Meniere's disease. However, even if given at intervals, a destruction of the cochlea was often observed in various animal models together with an increased content of nitric oxide (NO) and reactive oxygen species. The present study was undertaken to identify the correlation between hearing threshold alteration and the NO production in the lateral wall and organ of Corti of the guinea pig in response to gentamicin application. Study Design: Prospective animal study in guinea pigs. Methods: A single dose of gentamicin (10 mg/kg body weight) was injected intratympanally into male guinea pigs and the auditory b…