Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media.

Otitis media (OM), inflammation of the middle ear, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population and mouse models that there is a significant genetic component predisposing to OM, yet nothing is known about the underlying genetic pathways involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This develops from acute OM that arises spontaneously in the postnatal period, with the age of onset and early severity dependent on the microbiological status of the mice and their air quality. We have identified the causal mutation, a missense change in the C-terminal zinc finger region of the transcription factor Evi1. This protein is expressed in middle ear basal epithelial cells, fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when inflammatory changes are underway. The identification and characterization of the Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates a new pathway in genetic predisposition to OM.

A novel mutation in the WFS1 gene identified in a Taiwanese family with low-frequency hearing impairment.

BACKGROUND: Wolfram syndrome gene 1 (WFS1) accounts for most of the familial nonsyndromic low-frequency sensorineural hearing loss (LFSNHL) which is characterized by sensorineural hearing losses equal to and below 2000 Hz. The current study aimed to contribute to our understanding of the molecular basis of LFSNHL in an affected Taiwanese family. METHODS: The Taiwanese family with LFSNHL was phenotypically characterized using audiologic examination and pedigree analysis. Genetic characterization was performed by direct sequencing of WFS1 and mutation analysis. RESULTS: Pure tone audiometry confirmed that the family members affected with LFSNHL had a bilateral sensorineural hearing loss equal to or below 2000 Hz. The hearing loss threshold of the affected members showed no progression, a characteristic that was consistent with a mutation in the WFS1 gene located in the DFNA6/14/38 locus. Pedigree analysis showed a hereditarily autosomal dominant pattern characterized by a full penetrance. Among several polymorphisms, a missense mutation Y669H (2005T>C) in exon 8 of WFS1 was identified in members of a Taiwanese family diagnosed with LFSNHL but not in any of the control subjects. CONCLUSION: We discovered a novel heterozygous missense mutation in exon 8 of WFS1 (i.e., Y669H) which is likely responsible for the LFSNHL phenotype in this particular Taiwanese family.

Multiple analyses of factors related to complications in endoscopic sinus surgery.

BACKGROUND: This study was undertaken to evaluate whether endoscopic sinus surgery (ESS) with a microdebrider had an impact on complication rates, and to facilitate the determination of factors associated with complications in patients who underwent ESS at a tertiary referral center in Taiwan. METHODS: This investigation was a retrospective study and literature review. We analyzed 997 consecutive patients who underwent ESS at Mackay Memorial Hospital in Taipei, Taiwan from January 2006 through February 2010. All data including those of patient medical information, and peri- and postoperative complications were provided by the surgeons involved in patient medical care. We analyzed the complication rates using the following 10 variables by univariate analysis and multivariate logistic regression: sex, age, Lund-Mackay score, polyp grading, previous sinonasal surgery, surgeon skill, adjunctive sinonasal surgery, mesenteric type of anterior ethmoid artery, Keros skull base type, and the use of a microdebrider. RESULTS: Of the 997 patients in our study, 78 (7.8%) had complications. Major complications occurred in five patients (0.5%): two with cerebrospinal fluid rhinorrhea, one with medial rectus muscle damage, and two with retrobulbar hematoma. Minor complications were found in 73 patients (7.3%), which included 32 patients with perioperative estimated blood loss > 15% of the total estimated blood volume, 26 with lamina papyracea damage, two with orbital cellulitis, and 13 with postoperative bleeding. Univariate analysis showed that risk factors related to complication rate were advanced Lund-Mackay scores (scores 19-24), advanced polyp grading (Grades 2 and 3), inexperienced surgeon (resident), and microdebrider usage. However, multivariate analysis revealed that complication rate was linked to advanced Lund-Mackay scores (Scores 19-24), mesenteric type of anterior ethmoid artery, and inexperienced surgeon. CONCLUSION: Overall, the results of our study showed that the ESS complication rate was 7.8%, with risk factors including advanced Lund-Mackay scores (19-24, odds ratio 10.4) and inexperienced surgeon. It was also noted that ESS with a microdebrider had no impact on complication rates, although the presence of a mesenteric type of anterior ethmoid artery proved to be a protective factor.

Increased risk of depression in patients with acquired sensory hearing loss: A 12-year follow-up study.

Acquired sensory hearing loss (SHL) is suggested to be associated with depression. However, some studies have reported conflicting results. Our study investigated the relationship between the prevalence of SHL and the incidence of depression over 12 years of follow-up by using data from the Taiwan National Health Insurance Research Database (NHIRD). We sought to determine the association between SHL and subsequent development of depression and discuss the pathophysiological mechanism underlying the association.Patients with SHL were identified from the NHIRD (SHL cohort). A non-SHL cohort, comprising patients without SHL frequency-matched with the SHL patients according to age group, sex, and the year of diagnosis of SHL at the ratio of 1:4, was constructed, and the incidence of depression was evaluated in both cohorts. A multivariable model was adjusted for age, sex, and comorbidity.The SHL cohort and non-SHL cohort comprised 5043 patients with SHL and 20,172 patients without SHL, respectively. The incidences density rates were 9.50 and 4.78 per 1000 person-years in the SHL cohort and non-SHL cohort, respectively. After adjustment for age, sex, and comorbidities, the risk of depression was higher in the SHL cohort than in the non-SHL cohort (hazard ratio = 1.73, 95% confidence interval = 1.49-2.00).Acquired SHL may increase the risk of subsequent depression. The results demonstrated that SHL was an independent risk factor regardless of sex, age, and comorbidities. Moreover, a strong association between hearing loss and subsequent depression among Taiwanese adults of all ages, particularly those aged ≤49 and >65 years and without using steroids for the treatment of SHL was observed. Prospective clinical and biomedical studies on the relationship between hearing loss and depression are warranted for determining the etiopathology.

Intratympanic steroid injection as a first-line therapy in uremia patients with sudden sensorineural hearing loss.

CONCLUSIONS: ITSI as a first-line therapy in uremia patients with SSNHL offers a valid and safe treatment compared with intravenous systemic steroid treatment. A specific pathophysiology caused by possible sodium pump paralysis may be explained for uremia patients with SSNHL. OBJECTIVE: To compare the efficacy of intratympanic steroid injection (ITSI) with that of systemic intravenous steroids as a first-line therapy in uremia patients with sudden sensorineural hearing loss (SSNHL). MATERIALS AND METHODS: A total of 23 consecutive uremia patients with SSNHL were enrolled in this study. Patients were divided into two groups: the ITSI group (n = 15) and the non-ITSI group (n = 8), in which patients received intravenous systemic steroid treatment. The two groups were homogeneous in all respects. RESULTS: The hearing improvement and relative gain were statistically significant between the two groups. The value of hearing gain (ΔPTA = PTA pre - PTA post) in the ITSI group and the non-ITSI group was 24.6 ± 16.4dB and 8.4 ± 19.3dB. The value of relative gain (ΔPTA/PTApre) in the ITIS group and the non-ITSI group was 31.1 ± 22% and 9.4 ± 20.5%. In the ITSI group, 11 patients (73.3%) exhibited hearing recovery (ΔPTA > 10 dB).

Effectiveness of intratympanic dexamethasone injection in sudden-deafness patients as salvage treatment.

OBJECTIVE: To study the effectiveness of intratympanic dexamethasone (IT-DEX) in patients with severe or profound sudden sensorineural hearing loss (SSNHL) after treatment failure with conventional therapy. STUDY DESIGN: Randomized, controlled study. METHODS: Patients who met the criteria for SSNHL, with a severity of severe to profound, underwent 10 days of standard treatment with oral steroid and other facilitating agents. Patients showing poor response to standard treatment were assigned randomly to a control group or to a group receiving IT-DEX. IT-DEX injections were performed once a week for 3 consecutive weeks. Pure-tone audiometry was obtained before each injection. Minimum follow-up time was 1 month. Successful treatment was defined as a hearing improvement of greater than 30 dB. RESULTS: Thirty-nine patients meeting the inclusion criteria were studied. After treatment with oral steroid, 10 of 39 (26%) patients demonstrated hearing improvement, whereas the remaining 29 (74%) patients showed a hearing improvement of less than 30 dB. For those without hearing improvement, 15 received IT-DEX, and 14 received further standard treatment (except oral steroid and carbogen inhalation). Hearing improved in 8 of 15 (53.3%) compared with 1 of 14 (7.1%), with an average decrease in threshold of 28.4 dB and 13.2 dB for the IT-DEX group and the control group, respectively (P <.05). Prognostic factors such as age, treatment delay time, and sex did not significantly affect the response to therapy. CONCLUSIONS: IT-DEX injection effectively improves hearing in patients with severe or profound SSNHL after treatment failure with standard therapy and is not associated with major side effects. It is therefore a reasonable alternative as salvage treatment.

High-dose intratympanic gentamicin instillations for treatment of Meniere's disease: long-term results.

CONCLUSIONS: Administration of high-dose gentamicin for intractable Meniere's disease appears to be effective in achieving long-term control of vertigo. However, the safety of this route of administration with respect to the patient's hearing has not yet been sufficiently established. OBJECTIVES: The study aimed to analyze the long-term results of patients receiving high-dose intratympanic gentamicin (ITG) instillation for refractory Meniere's disease. PATIENTS AND METHODS: Fourteen patients with Meniere's disease according to 1995 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines who had failed medical (12 subjects) or surgical (2 subjects) treatment were included. Intratympanic injections of 27 mg/ml gentamicin were performed three times daily for 4 days. Vertigo control, the patients' functional level, and their hearing threshold were all analyzed. Criteria described in 1995 by AAO-HNS were used. RESULTS: The overall successful vertigo control rate was 92.9% over the 2-year follow-up and 85.7% at long-term follow-up (average 10 years). Hearing level as pure-tone average was worse in four patients (28.5%) after 2 years follow-up and in six patients (42.8%) after long-term follow-up, respectively. Profound sensorineural hearing loss occurred as a result of gentamicin injection in one patient (7%).