Cochlea cell-specific marker expression upon in vitro Hes1 knockdown.

NOTCH pathway proteins, including the transcriptional factor HES1, play crucial roles in the development of the inner ear by means of the lateral inhibition mechanism, in which supporting cells have their phenotype preserved while they are prevented from becoming hair cells. Genetic manipulation of this pathway has been demonstrated to increase hair cell number. The present study aimed to investigate gene expression effects in hair cells and supporting cells after Hes1-shRNA lentivirus transduction in organotypic cultures of the organ of Corti from postnatal-day-3 mice. Forty-eight hours after in vitro knockdown, Hes1 gene expression was reduced at both mRNA and protein levels. Myo7a (hair cell marker) and Sox2 (progenitor cell marker) mRNA levels also significantly increased. The modulation of gene expression in the organ of Corti upon Hes1 knockdown is consistent with cell phenotypes related to lateral inhibition mechanism interference in the inner ear. The lentivirus-based expression of Hes1-shRNA is a valuable strategy for genetic interference in the organ of Corti and for future evaluation of its efficacy in protocols aiming at the regeneration of hair cells in vivo.

Cochlea cell-specific marker expression upon in vitro Hes1 knockdown

NOTCH pathway proteins, including the transcriptional factor HES1, play crucial roles in the development of the inner ear by means of the lateral inhibition mechanism, in which supporting cells have their phenotype preserved while they are prevented from becoming hair cells. Genetic manipulation of this pathway has been demonstrated to increase hair cell number. The present study aimed to investigate gene expression effects in hair cells and supporting cells after Hes1-shRNA lentivirus transduction in organotypic cultures of the organ of Corti from postnatal-day-3 mice. Forty-eight hours after in vitro knockdown, Hes1 gene expression was reduced at both mRNA and protein levels. Myo7a (hair cell marker) and Sox2 (progenitor cell marker) mRNA levels also significantly increased. The modulation of gene expression in the organ of Corti upon Hes1 knockdown is consistent with cell phenotypes related to lateral inhibition mechanism interference in the inner ear. The lentivirus-based expression of Hes1-shRNA is a valuable strategy for genetic interference in the organ of Corti and for future evaluation of its efficacy in protocols aiming at the regeneration of hair cells in vivo.

Endolymphatic sac drainage for the treatment of Ménière's disease.

OBJECTIVE: To describe the results obtained with endolymphatic sac drainage in patients with Ménière's disease. METHOD: A retrospective case review study was conducted of 95 Ménière's disease patients who underwent endolymphatic sac drainage in a tertiary care referral centre, after failing a long course of medical management. The main outcome measures were vertigo control and hearing preservation. RESULTS: In patients with unilateral disease, vertigo control was obtained in 94.3 per cent of patients. A significant improvement in cochlear function was seen in 14 per cent of patients, and hearing was preserved or improved in 88 per cent. For the bilateral group, vertigo control was obtained in 85.7 per cent of patients and cochlear function improved in 28 per cent. Hearing preservation was attained in 71 per cent of these patients. CONCLUSION: Endolymphatic sac drainage is a good surgical option for patients with incapacitating endolymphatic hydrops, providing a high percentage of vertigo control and hearing preservation.

Transplantation and survival of mouse inner ear progenitor/stem cells in the organ of Corti after cochleostomy of hearing-impaired guinea pigs: preliminary results.

In mammals, damage to sensory receptor cells (hair cells) of the inner ear results in permanent sensorineural hearing loss. Here, we investigated whether postnatal mouse inner ear progenitor/stem cells (mIESCs) are viable after transplantation into the basal turns of neomycin-injured guinea pig cochleas. We also examined the effects of mIESC transplantation on auditory functions. Eight adult female Cavia porcellus guinea pigs (250-350 g) were deafened by intratympanic neomycin delivery. After 7 days, the animals were randomly divided in two groups. The study group (n=4) received transplantation of LacZ-positive mIESCs in culture medium into the scala tympani. The control group (n=4) received culture medium only. At 2 weeks after transplantation, functional analyses were performed by auditory brainstem response measurement, and the animals were sacrificed. The presence of mIESCs was evaluated by immunohistochemistry of sections of the cochlea from the study group. Non-parametric tests were used for statistical analysis of the data. Intratympanic neomycin delivery damaged hair cells and increased auditory thresholds prior to cell transplantation. There were no significant differences between auditory brainstem thresholds before and after transplantation in individual guinea pigs. Some mIESCs were observed in all scalae of the basal turns of the injured cochleas, and a proportion of these cells expressed the hair cell marker myosin VIIa. Some transplanted mIESCs engrafted in the cochlear basilar membrane. Our study demonstrates that transplanted cells survived and engrafted in the organ of Corti after cochleostomy.

Transplantation and survival of mouse inner ear progenitor/stem cells in the organ of Corti after cochleostomy of hearing-impaired guinea pigs: preliminary results

In mammals, damage to sensory receptor cells (hair cells) of the inner ear results in permanent sensorineural hearing loss. Here, we investigated whether postnatal mouse inner ear progenitor/stem cells (mIESCs) are viable after transplantation into the basal turns of neomycin-injured guinea pig cochleas. We also examined the effects of mIESC transplantation on auditory functions. Eight adult female Cavia porcellus guinea pigs (250-350g) were deafened by intratympanic neomycin delivery. After 7 days, the animals were randomly divided in two groups. The study group (n=4) received transplantation of LacZ-positive mIESCs in culture medium into the scala tympani. The control group (n=4) received culture medium only. At 2 weeks after transplantation, functional analyses were performed by auditory brainstem response measurement, and the animals were sacrificed. The presence of mIESCs was evaluated by immunohistochemistry of sections of the cochlea from the study group. Non-parametric tests were used for statistical analysis of the data. Intratympanic neomycin delivery damaged hair cells and increased auditory thresholds prior to cell transplantation. There were no significant differences between auditory brainstem thresholds before and after transplantation in individual guinea pigs. Some mIESCs were observed in all scalae of the basal turns of the injured cochleas, and a proportion of these cells expressed the hair cell marker myosin VIIa. Some transplanted mIESCs engrafted in the cochlear basilar membrane. Our study demonstrates that transplanted cells survived and engrafted in the organ of Corti after cochleostomy.

Prevalence of chronic rhinosinusitis in Sao Paulo.

INTRODUCTION: Studies designed to investigate chronic rhinosinusitis (CRS) epidemiology play an important role to assess population`s distribution and risk factors to result in the development and promotion of public health policies. METHOD: This study design is a survey carried out with a complex two-stage cluster sampling plan. Personal interviews were carried out with 2,003 individuals. The questionnaire included the epidemiological criteria for CRS. Demographic data, history of physician-diagnosed respiratory diseases (asthma, sinusitis, rhinitis), smoking, family income, educational attainment, and household characteristics were also evaluated. RESULTS: The overall response rate was 93.9% of the households. Mean age was 39.8 +- 21 years; 45.33% were male. The overall prevalence of CRS in the city of Sao Paulo was 5.51%. We found a significant association between diagnosis of CRS and diagnosis of asthma and CRS and diagnosis of rhinitis and a significant association between presence of CRS and belonging to the low-income subgroup. CONCLUSION: The municipality of Sao Paulo has an urban population of 11 million. According to the present study, the prevalence of CRS is 5.51%, which represents more than 500,000 individuals affected by this condition in the city.

Hearing loss in diffuse cutaneous systemic scleroderma.

OBJECTIVES: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have distinct clinical manifestations, usually with more aggressive organ involvement and highermortality than limited cutaneous systemic sclerosis (lcSSC). Hearing loss had not yet been evaluated in this subtype, so our aim was to assess the auditory system of dcSSc patients in a controlled study. METHODS: Twenty-six patients with dcSSc, according to American College of Rheumatology (ACR) criteria, were evaluated. For each dcSSc patient included in the study, two healthy controls were matched for sex and age (± 2 years). All patients responded to a structured questionnaire regarding otological symptoms and risk factors with regard to hearing loss. A complete ear/nose/throat physical examination was performed followed by speech/pure tone audiometry and impedance measurements. RESULTS: The mean age of the dcSSc patients was 47.0 ± 11.9 years; the mean disease duration was 9.4 ± 9.1 years, and there was a clear female predominance (83%). The questionnaire revealed auditory complaints in 54% of the dcSSc patients (25% hearing loss, 21% aural fullness, 21% tinnitus, and 21% dizziness) and normal otoscopy. Nearly half (46%) of the dcSSc patients were diagnosed as having hearing loss on audiogram compared to only 19% in the control group (p = 0.01). All dcSSc with hearing loss had a sensorineural component, eight (73%) with excellent discrimination on the Percentage Index of Speech Recognition (PISR). Descending configuration and Metz recruitment were observed in 54% of these patients, suggesting cochlear involvement. CONCLUSION: Patients with dcSSc have a high prevalence of sensorineural audiometric hearing impairment and otological complaints, suggesting that the cochlea is an additional target organ in this disease.

Anaglyphic three-dimensional stereoscopic printing: revival of an old method for anatomical and surgical teaching and reporting.

The authors describe how to use the three-dimensional (3D) anaglyphic method to produce stereoscopic prints for anatomical and surgical teaching and reports preparation by using currently available nonprofessional photographic and computer methods. As with any other method of producing stereoscopic images, the anaglyphic procedure is based on the superimposition of two slightly different images of the object to be reproduced, one seen more from a left-sided point of view and the other seen more from a right-sided point of view. The pictures are obtained using a single camera, which following the first shot can be slid along a special bar for the second shot, or by using two cameras affixed to a surgical microscope. After the images have been distinguished from each other by applying different complementary color dyes, the images are scanned and superimposed on each other with the aid of nonprofessional imaging-manipulation software used on a standard personal computer (PC), and are printed using a standard printer. To be seen stereoscopically, glasses with colored lenses, normally one red and one blue, have to be used. Stereoscopic 3D anaglyphic prints can be produced using standard photographic and PC equipment; after some training, the prints can be easily reproduced without significant cost and are particularly helpful to disclose the 3D character of anatomical structures.

Magnetic resonance imaging of the temporal bone in patients with Ménière's disease.

Ménière's disease (MD) is still controversial in several aspects. The vestibular aqueduct, the osseous channel that carries the endolymphatic duct and sac, has previously been studied by tomography and computed tomography, with shortening and narrowing of this structure observed. These findings are apparently correlated to the development of the endolymphatic hydrops present in MD and related to its episodic symptoms. In studying the endolymphatic duct, the key structure in the pathology of this disease, magnetic resonance imaging (MRI) studies of the temporal bone were performed in 12 patients with unilateral MD and in 9 bilateral cases; the results were compared with images obtained from 30 normal ears. The endolymphatic duct appeared to be statistically less visible in MD patients, with no difference between symptomatic and asymptomatic ears in the presence of unilateral disease. No relationship was found between visualization of the endolymphatic duct and time of evolution or response to clinical treatment in these cases. The distance from the posterior semicircular canal to the posterior temporal border was found to be bilaterally reduced in MD. The authors conclude that although the demonstration of endolymphatic hydrops "in vivo" is not yet possible by MRI, some features can be observed that can support a clinical hypothesis of MD.

Lidocaine test in patients with tinnitus: rationale of accomplishment and relation to the treatment with carbamazepine.

OBJECTIVES: There is strong evidence in the literature about the effect of local anesthetics such as lidocaine in controlling tinnitus; these agents act by stabilizing hair cell membrane and cochlear nerve fibers. However, the effect of intravenous lidocaine is transient, and its oral analog (tocainide) does not have the same efficacy for long-term treatment in patients with tinnitus. Some oral anti-epileptic drugs (carbamazepine, for instance) have been used alternatively in several studies. The aim of this work is to evaluate the response to intravenous lidocaine in patients with intractable tinnitus and the effect of oral carbamazepine in long-term maintenance of tinnitus relief. PATIENTS AND METHODS: We studied prospectively 50 patients (28 females and 22 males; mean age 50.9 years) who underwent the lidocaine test, performed by a 3-min intravenous infusion of 2% lidocaine chloridrate. The patients who experienced any relief after the test started treatment with oral carbamazepine in ascending dosages (50-600 mg/day). RESULTS: The results were classified as tinnitus abolition (18%), marked relief (32%), partial relief (26%), unchanged (22%), or worsening (2%). The lidocaine test showed favorable results in 76% of patients, especially those with bilateral tinnitus (P < 0.001). Afterwards, 50% of patients treated with carbamazepine maintained the improvement of tinnitus (P = 0.0034). CONCLUSION: The authors conclude that intravenous lidocaine is effective in reducing intractable tinnitus and that there is a close association between lidocaine and oral carbamazepine effects. Therefore, carbamazepine can be used for the treatment of tinnitus when the patient achieves improvement of symptom after the lidocaine test.

Continuous, high-frequency objective tinnitus caused by middle ear myoclonus.

Myoclonus of the middle ear is a rare condition characterized by abnormal repetitive muscle contractions of the tympanic cavity. In this paper we describe what we believe is the first reported case of continuous high-frequency objective tinnitus caused by middle ear myoclonus. During exploratory tympanomastoidectomy it was hypothesized that a small dural arteriovenous malformation not identified on previous tests was the cause of the tinnitus. However, complete disappearance of the tinnitus during administration of curare for anesthesia led us to believe that the tinnitus might have been caused by myoclonus of the middle ear. Sectioning of the stapedius and tensor tympani tendons rendered the patient asymptomatic and confirmed the diagnosis of middle ear myoclonus. At follow-up of one year, the patient's quality of life had improved substantially; the tinnitus did not recur and she no longer had vertigo.

Otological lesions in pachyonychia congenita syndrome.

The authors report a case of a patient with pachyonychia congenita syndrome, a rare genodermatosis inherited as an autosomal dominant trait, who also had otological lesions beyond the other classic signs and symptoms of the syndrome. Many kinds of treatment have already been proposed, but all failed to show satisfactory results. A new, cheap and easy-to-use treatment was developed in this study, using keratoplastics interpolated with humectant lotion for 90 days. The results after three years of follow-up are still thoroughly satisfactory.

A pathway for information transmission to the ear.

The use of implantable hearing aids and cochlear implants as an aid to neurosensory deafness is becoming an established procedure. The transmission of a processed speech signal is accomplished either transcutaneously via radiofrequency or percutaneously by connector coupling. Whereas the former is sensitive to electromagnetic interference, the latter increases the risk of infection. To overcome these disadvantages, an infrared (IR) system for transmission through the tympanic membrane was devised and tested. The transmitter/receiver consisted of an IR light emitting diode (LED; 920nm) and a photovoltaic cell. The LED was placed inside the auditory canal of four dogs and the photovoltaic cell in the tympanic cavity over the cochlear promontory. A sinusoidal signal modulation was applied to the LED. The emitted signal was detected undistorted after crossing the tympanic membrane, with an average absorbance of 20%. High-frequency cut-off was adequate for cochlear implant purposes and audio prosthetic devices in general. The authors conclude that the tympanic membrane may be used as a translucent sealed interface to transmit data in the audio range to the middle and inner ears, with small power loss, good frequency response, and immunity to interface.

Anastomosis of the intratemporal facial nerve using fibrin tissue adhesive.

This work aimed at studying the results obtained by the repair of complete lesions of the facial nerve in its intratemporal portions. Clinical, electrophysiological and surgical techniques were studied. Twenty-three patients with traumatic facial nerve lesions were operated. Nerve grafts were made in 10, and end-to-end anastomosis in thirteen. The surgical technique performed was the coaptation of the stumps and stabilization with fibrin tissue adhesive. Sixteen months after surgery, a clinical and electrophysiological evaluation was made. The use of fibrin tissue adhesive to stabilize intratemporal anastomosis of facial nerve showed clinical and electrophysiological evidence of axonal growth and reinnervation of mimical muscles of the face. These results were similar to that obtained by other authors that used other methods of microanastomosis. The use of fibrin tissue adhesive is an effective technique to utilize in intratemporal anastomosis of the facial nerve.

Human lagochilascariasis treated successfully with ivermectin: a case report.

A 15 year old male patient was diagnosed as being infected with the nematode Lagochilascaris minor, presenting as abscesses over the left mastoid region, and invading the temporal bone, mastoid sinuses and possibly the CNS. Surgical drainage and administration of cambendazole and levamisole led to improvement, followed by an early relapse and poor tolerance to the antihelminthic drugs. Repeated doses of ivermectin (an animal preparation) were used for the first time to treat this condition and resulted in complete remission of signs of infection, maintained for 15 months after the end of drug therapy, indicating cure of the disease.

[Tumors of the ceruminous glands: revision of the literature and report of a case in the middle ear]. / Tumeurs de glandes cérumineuses: révision de la littérature et présentation d'un cas dans l'oreille moyenne.

The ceruminous glands tumors are very rare pathologies, being even rarer their origin other then the external auditory canal. In this paper, we report a case of ceruminous adenoma of the middle ear and study other 125 cases related in the literature since 1941. We analyze the incidence of each hystological type, the sex, race, age and site of origin of the tumors.