The Role of MRI in Diagnosing Neurovascular Compression of the Cochlear Nerve Resulting in Typewriter Tinnitus.

BACKGROUND AND PURPOSE: Typewriter tinnitus, a symptom characterized by paroxysmal attacks of staccato sounds, has been thought to be caused by neurovascular compression of the cochlear nerve, but the correlation between radiologic evidence of neurovascular compression of the cochlear nerve and symptom presentation has not been thoroughly investigated. The purpose of this study was to examine whether radiologic evidence of neurovascular compression of the cochlear nerve is pathognomonic in typewriter tinnitus. MATERIALS AND METHODS: Fifteen carbamazepine-responding patients with typewriter tinnitus and 8 control subjects were evaluated with a 3D T2-weighted volume isotropic turbo spin-echo acquisition sequence. Groups 1 (16 symptomatic sides), 2 (14 asymptomatic sides), and 3 (16 control sides) were compared with regard to the anatomic relation between the vascular loop and the internal auditory canal and the presence of neurovascular compression of the cochlear nerve with/without angulation/indentation. RESULTS: The anatomic location of the vascular loop was not significantly different among the 3 groups (all, P > .05). Meanwhile, neurovascular compression of the cochlear nerve on MR imaging was significantly higher in group 1 than in group 3 (P = .032). However, considerable false-positive (no symptoms with neurovascular compression of the cochlear nerve on MR imaging) and false-negative (typewriter tinnitus without demonstrable neurovascular compression of the cochlear nerve) findings were also observed. CONCLUSIONS: Neurovascular compression of the cochlear nerve was more frequently detected on the symptomatic side of patients with typewriter tinnitus compared with the asymptomatic side of these patients or on both sides of control subjects on MR imaging. However, considering false-positive and false-negative findings, meticulous history-taking and the response to the initial carbamazepine trial should be regarded as more reliable diagnostic clues than radiologic evidence of neurovascular compression of the cochlear nerve.

Occupational exposure and idiopathic pulmonary fibrosis: a multicentre case-control study in Korea.

SETTING: Multicentred hospital-based cases and control subjects in Korea. OBJECTIVE: To evaluate the association between idiopathic pulmonary fibrosis (IPF) and hazardous materials to which people are occupationally exposed. DESIGN: A multicentre, hospital-based, matched case-control study was performed. The ratio of IPF cases to controls was 1:1 (n = 78 in each group). IPF cases and controls were matched in terms of age group, sex and place of residence. Conditional logistic regression analysis was performed. RESULTS: In simple logistic regression analysis, exposure to metal dust and any exposure for >1 year in an occupational setting were significantly associated with IPF (metal dust OR 4.00, 95%CI 1.34-11.97; any exposure OR 3.67, 95%CI 1.02-13.14). After adjustment for environmental and military exposures and smoking history, the OR for metal dust exposure was 4.97 (95%CI 1.36-18.17) in multiple logistic regression analysis. CONCLUSIONS: Metal dust was associated with incident IPF in Seoul and Gyeonggi Provinces in Korea. This information will be used to support a tailored preventive strategy in specific industries or occupations.

Health care burden and medical resource utilisation of idiopathic pulmonary fibrosis in Korea.

SETTING: Despite the clinical importance of idiopathic pulmonary fibrosis (IPF), its epidemiology has been rarely reported. The economic burden from IPF is therefore difficult to predict. OBJECTIVE: To analyse the health care burden and current situation with respect to medical resource utilisation in patients with IPF in Korea. METHODS: We analysed nationwide data collected between 2009 and 2013 from the Korean Health Insurance Review and Assessment (HIRA) database. Patients with IPF were defined by the K-J84.18 code of the Korean Classification of Disease, 6th revision. RESULTS: The total direct health care costs increased from US$19 805 167 in 2009 to US$31 410 083 in 2013; the principal factor responsible for the highest proportion of costs was hospitalisation. The proportion of the total IPF patient population who were hospitalised at least once a year was 27.2%, and the average length of hospital stay was 12.7 days. From post-hoc analysis, hospital admission, emergency room visit and intensive care unit admission rates showed significant seasonal variations; the admission rates were highest in the spring and lowest in autumn. CONCLUSIONS: Health care costs of IPF are increasing annually, with hospital admissions representing the major financial burden.

Incidence and prevalence of idiopathic interstitial pneumonia and idiopathic pulmonary fibrosis in Korea.

SETTING: Although the incidence and prevalence of idiopathic interstitial pneumonia (IIP) and idiopathic pulmonary fibrosis (IPF) have been assessed in Western countries, their epidemiology has not been analysed in Asian countries, including the Republic of Korea. OBJECTIVE: To estimate the prevalence and incidence of IIP, including IPF, in Korea, using a large, nationwide database. DESIGN: The Health Insurance Review and Assessment Services claims database, which includes information on every patient with diagnostic codes for IPF and IIP from 2010 to 2013, was reviewed. Age- and sex-specific IPF and IIP prevalence and incidence rates were estimated. RESULTS: Among Korean males and females, IPF prevalence from 2010 to 2013 was estimated at respectively 39.7 and 24.3 per 100 000 population, while IIP prevalence was estimated at respectively 97.1 and 66.5/100 000. The annual incidence rates among Korean males and females during 2011 and 2012 were respectively 16.4 and 9.7/100 000, for IPF, and respectively 42.3 and 27.5/100 000 for IIP. CONCLUSIONS: IPF is more prevalent in Korea than previously reported; its prevalence may be similar to or higher than in the United States and in European countries.

Risk factors for lung function impairment among the general non-smoking Korean population.

SETTING: Nationwide general population in South Korea. OBJECTIVE: Except for tobacco smoking, risk factors for the impairment of lung function have not been widely evaluated. We evaluated the risk factors for lung function impairment among the general non-smoking Korean population. DESIGN: A total of 8164 non-smokers from the spirometry data set of the Korean National Health and Nutrition Examination Surveys IV and V (2008-2010) were included in the study. After sex stratification, multiple survey logistic regression analyses were performed to estimate the association between potential risk factors and impaired lung function in this nationwide cross-sectional study. RESULTS: The proportion of non-smokers among the general Korean population with forced expiratory volume in 1 s (FEV1) < 80% of predicted, forced vital capacity (FVC) < 80% of predicted and FEV1/FVC ratio < 0.7 were respectively 46.2%, 50.3% and 30.2%. In multiple survey logistic regression analyses, lung function impairment was associated with tuberculosis (TB) and asthma in female non-smokers and asthma in male non-smokers. CONCLUSIONS: TB and asthma are risk factors for lung function impairment among Korean non-smokers. To prevent further lung function impairment, a careful control system for these factors should be considered when setting health policy priorities.

Dose-related effect of urinary cotinine levels on pulmonary function among Korean women.

SETTING: Country-wide general population in South Korea. BACKGROUND: The dose-response relationship between smoking and pulmonary function in women may have been significantly over-estimated by studies that employed a self-reporting questionnaire. OBJECTIVE: To evaluate whether this relationship was still observed among Korean women when smoking levels were determined by urinary cotinine measurements. DESIGN: A total of 4584 Korean women from the spirometry data set of the Korean National Health and Nutrition Examination Surveys IV and V (2008-2010) were included. Analysis of covariance was performed to estimate the dose-related effect of urinary cotinine levels on pulmonary function after adjusting for covariates in this country-wide cross-sectional study. RESULTS: Compared to urinary cotinine levels (cut-off 50 ng/ml), the false-positive rate of self-reported smoking was 53.2%. After the smokers were divided into deciles, the regression coefficients for percentage forced expiratory volume in 1 second (FEV1%) and percentage forced expiratory volume/forced volume capacity (FEV1/FVC) ratio (FEV1/FVC%) were -0.2903 and -0.2680 (%/decile), respectively (both P < 0.001). CONCLUSION: It is necessary to use objective methods when determining the smoking status of Korean women. Even after reducing information bias, smoking affected pulmonary function in a dose-dependent manner.

Dose-related effect of urinary cotinine levels on bone mineral density among Korean females.

UNLABELLED: To evaluate the dose-dependent relationship between smoking and bone mineral density (BMD), the present study used the BMD dataset of the Korean National Health and Nutrition Examination Survey IV (KNHANES IV). The linearity of BMD for urinary cotinine levels was demonstrated with statistical significance in postmenopausal females. INTRODUCTION: It is well established that smoking is an important lifestyle risk factor for bone health (bone loss, osteoporosis, and fracture). However, several studies demonstrated conflicting evidence for a dose-dependent relationship between smoking and bone health. To evaluate the dose-dependent relationship between smoking and BMD, the present study estimated dose-related effects of smoking (urinary cotinine level) on BMD at various sites (femur neck, total femur, and lumbar spine) in females with controlling menopausal status. METHODS: The present study used the BMD dataset of the KNHANES IV, which was performed in 2008 and 2009. A total of 4,260 pre- and postmenopausal females were included in the present study. Dose-response relationships between BMD and urinary cotinine levels were estimated using analysis of covariance in pre-menopausal females and postmenopausal females, respectively. RESULTS: In postmenopausal females, the regression coefficients for BMD with urinary cotinine levels were -0.006, -0.006, and -0.008 (g/cm2 per ng/ml) at femur neck, total femur, and lumbar spine, respectively (p value<0.05). Thus, the linearity of BMD for urinary cotinine levels was demonstrated with statistical significance in postmenopausal females. CONCLUSION: Our findings suggested a significant dose-related effect of urinary cotinine level with BMD at femur neck, total femur, and lumbar spine among postmenopausal females.

Osteopenia and osteoporosis in idiopathic benign positional vertigo.

OBJECTIVE: Causes of benign positional vertigo (BPV) are mostly unknown. The aim of this study was to elucidate an association of osteoporosis with idiopathic BPV. METHODS: Two hundred nine consecutive patients with a confirmed diagnosis of idiopathic BPV underwent bone mineral densitometry of anterior-posterior lumbar spine and femur. The T scores were compared with those of 202 controls without a history of dizziness. Recurrence was defined when the patients reported two or more previous episodes of positional vertigo similar to those experienced at the time of diagnosis. RESULTS: In both women and men, the lowest T scores were decreased in patients with BPV compared with those in controls. Furthermore, the prevalences of osteopenia (-2.5 < T score < -1.0) and osteoporosis (T score < or =-2.5) were higher in both women and men with BPV than in controls. Multiple logistic regression analyses adjusted for age, sex, alcohol, smoking, and hyperphosphatemia showed that only the existence of osteopenia/osteoporosis was associated with an increased risk of BPV (adjusted odds ratio of osteopenia = 2.0, 95% confidence interval 1.2-3.4, p = 0.011; adjusted odds ratio of osteoporosis = 3.1, 95% confidence interval 1.4-7.2, p = 0.007). In women aged > or =45 years, the lowest T scores were also decreased in the recurrent group, compared with those in the de novo group. CONCLUSION: Osteopenia/osteoporosis may be associated with idiopathic benign positional vertigo (BPV). The effectiveness of measuring bone mineral densitometry and restoring normal calcium metabolism for preventing recurrences of BPV requires further validation.

Hyperventilation-induced nystagmus in peripheral vestibulopathy and cerebellopontine angle tumor.

OBJECTIVE: To determine the incidence and characteristics of hyperventilation-induced nystagmus (HIN) in cerebellopontine angle (CPA) tumors and unilateral peripheral vestibulopathy (UPV), and to elucidate differential contribution of hyperventilation to bring out vestibular asymmetry between acute and chronic phases of UPV. METHODS: We recorded horizontal HIN in 33 patients with CPA tumors and 145 with UPV. The UPV included patients of either acute (7 days or less from symptom onset, n = 47) or chronic (more than 7 days from symptom onset, n = 98) phases. RESULTS: The incidence of HIN was higher in the CPA tumor than in the UPV group (82 vs 34%, p < 0.01) and was also higher in the acute than in the chronic UPV group (60 vs 21%, p < 0.01). Furthermore, HIN was more commonly ipsilesional (i-HIN) in the CPA tumor than in the UPV group (52 vs 8%, p < 0.01) and more commonly ipsilesional in the acute than in the chronic UPV group (21 vs 1%, p < 0.01). The patients with i-HIN and acoustic neuroma had a tendency to harbor smaller tumors and to have less severe caloric asymmetry. CONCLUSIONS: The contribution of hyperventilation on vestibular nystagmus differs depending on the disease phase or underlying pathologies. Our study demonstrates that hyperventilation-induced nystagmus (HIN) beating to the side of reduced caloric response, hearing impairment, or abnormal auditory brainstem response responses may be a valuable sign for bedside detection of cerebellopontine angle (CPA) tumors. CPA tumor should be a prime suspicion in patients with acute vertigo and ipsilesional HIN, especially when the vertigo accompanies hearing impairments.

Head-shaking nystagmus in lateral medullary infarction: patterns and possible mechanisms.

OBJECTIVE: Horizontal head shaking at 2 to 3 Hz can induce nystagmus in patients with central as well as in patients with peripheral vestibulopathy. However, the characteristics and diagnostic value of this post-head-shaking nystagmus (HSN) have not been studied systematically in central vestibulopathy, and little is known of the mechanisms involved. METHODS: We analyzed spontaneous and HSN and the effects of baclofen, a GABA(B) agonist, in 16 patients with acute lateral medullary infarction. RESULTS: These patients showed several characteristics of HSN unlike those observed in peripheral vestibulopathy. HSN was observed in 14 of 16 patients (87.5%), and in all cases, the horizontal component beats toward the lesion side, i.e., was ipsilesional. Even in the eight patients with contralesional spontaneous horizontal nystagmus, the HSN was opposite to the spontaneous nystagmus. Three patients showed unusually strong HSN with a maximum slow-phase velocity greater than 60 degrees/second. Visual fixation markedly suppressed HSN and baclofen reduced HSN. In most of the patients, MRI showed infarctions in the caudal or middle portion of the medulla and spared the rostral portion. CONCLUSIONS: We propose that head-shaking nystagmus in lateral medullary infarction is due to unilaterally impaired nodulouvular inhibition of the velocity storage. This proposal is consistent with the results of neuroanatomic studies that demonstrate that Purkinje cells controlling velocity storage in the nodulus and ventral uvula project to the caudal or middle portion of the vestibular nuclei, whereas those subserving visual-vestibular interactions in the flocculus project to the more rostral portion.

Serotonin-induced plasma extravasation in the murine inner ear: possible mechanism of migraine-associated inner ear dysfunction.

Sensitivity to sound and vertigo are often components of migraine. Recent studies suggest that plasma extravasation from intradural blood vessels may contribute to migraine pain. This study documented plasma extravasation in the mouse inner ear after intravenous administration of serotonin (5-HT). Horseradish peroxidase (HRP) was injected intravenously to trace protein extravasation in mice, followed 15 min later by intravenous 5-HT or saline. Forty-five minutes later, mice were euthanized. HRP extravasation was visualized immunohistochemically and quantified densitometrically. Baseline and evoked extravasation in stria vascularis and tectorial membrane were indistinguishable from skin, dura mater and tympanic membrane. Brain parenchyma, Scarpa's ganglion, basal spiral ganglion and modiolus, and the central vestibular nerve segment showed no significant 5-HT-induced extravasation. In contrast, 5-HT produced extravasation in the apical spiral ganglion, modiolus, and intralabyrinthine superior and inferior vestibular nerve. Thus, inner ear plasma extravasation is a potential mechanism for migraine-associated vertigo and sound sensitivity.

Rotational vertebral artery syndrome: oculographic analysis of nystagmus.

In four patients with rotational vertebral artery syndrome (RVAS), the initial nystagmus was mostly downbeat, with the horizontal and torsional components beating toward the compressed vertebral artery side (n = 3) or directed away (n = 1). Three patients showed spontaneous reversal of the nystagmus and two exhibited no or markedly diminished responses on immediate retrial of head rotation (habituation). The patterns of nystagmus suggest that RVAS may result from differing mechanisms.

Association of HLA-DR and type II collagen autoimmunity with Meniere's disease.

To investigate HLA-associated genetic susceptibility to Meniere's disease in relation to type II collagen (CII) autoimmunity status, HLA-DRB1 genotyping and ELISA measurement of anti-CII antibody were performed in 41 Korean patients with Meniere's disease. In the anti-CII positive subgroup (20%) of patients, the frequency of HLA-DRB1*0405 was significantly increased (uncorrected) compared with both controls (63% vs 16%) and anti-CII negative patients (63% vs 12%). In the anti-CII negative subgroup, HLA-DRB1*1201 was significantly increased (uncorrected) (27% vs 10%) and DRB1*13 was decreased (6% vs 24%) compared with controls; these alleles appeared to confer susceptibility and resistance to the development of the disease. Association of HLA-DRB1*0405 with anti-CII positive Meniere's disease in this study suggests that it shares a specific HLA-DR sequence, QRRAA, as a genetic susceptibility factor with the anti-CII positive rheumatoid arthritis. In conclusion, whilst type II collagen autoimmunity may have a partial role in Meniere's disease, different HLA-DR alleles may also be associated with either susceptibility or resistance to the development of the disease in relation to anti-CII antibody status.

Association of angiotensin I converting enzyme gene polymorphism with reflux nephropathy in children.

Deletion polymorphism of angiotensin I converting enzyme (ACE) gene has been studied as a risk factor in various cardiovascular diseases and chronic nephropathies. Perturbation of local and systemic renin-angiotensin systems is one of the possible mechanisms of the progression of reflux nephropathy. In this study, the implication of ACE gene polymorphism in renal scarring and deterioration of renal function was analyzed in 66 children with vesicoureteral reflux. The genotype for the polymorphism was determined by PCR, and renal scar was identified by (99m)Tc-DMSA renal scan. The allelic frequency of the deletion polymorphism showed no significant difference either between patients with normal renal function and those with decreased renal function or between patients with renal scar and those without. We conclude that deletion polymorphism of ACE gene, as an independent variable, is not associated with reflux nephropathy in children with vesicoureteral reflux.

Cationic liposome-enhanced adenoviral gene transfer in a murine head and neck cancer model.

The effect of combining adenoviral vector and cationic liposomes on the efficiency of gene transfer to head and neck tumor cells was investigated. Two human and two murine cell lines were used for the screening of gene transfer efficiency using an adenoviral vector. Cationic liposome-enhanced gene transfer was checked using a murine squamous carcinoma cell line, SCCVII/SF. A considerable difference in the efficiency of gene transduction was observed among the cell lines. The combination of DOSPER and adenoviral vector containing human alkaline phosphatase showed a remarkable enhancing effect in gene transfer in vitro and in vivo, compared to the adenovirus alone or control groups. With an improvement in the efficiency of gene transfer, it may be possible not only to enhance the expression of transduced genes, but also to deliver a smaller amount of virus, as a result, reducing toxicity and the immune response against adenovirus.

Expression of heat shock protein 72 in rat cochlea with cisplatin-induced acute ototoxicity.

Cisplatin ototoxicity is known to involve mainly the organ of Corti. Outer hair cells (OHCs). especially in the basal turn, are preferentially involved. One possible mechanism of ototoxicity might be alteration of the antioxidant system causing an increase in free radicals. It has been demonstrated that heat shock proteins (HSPs), which are believed to protect cells by dissolving and refolding misfolded or denatured protein are induced by various form of stress. HSP is also demonstrated to be induced by free radicals. The purpose of this study was to evaluate HSP 72 induction in cochlea following cisplatin injection in the animal model. Sprague-Dawley (SD) rats were injected intraperitoneally with normal saline as control or cisplatin at a dose of 5, 10 or 20 mg/kg. Cochleae were harvested 1, 3, 6 and 12 h after injection and compared with those of controls. Immunocytochemical study with surface preparation and Western blotting were performed to investigate the expression of HSP 72. Auditory brainstem response (ABR) was also recorded to assess functional change according to the dosage of cisplatin and duration after injection. In the 5 and 10 mg/kg groups, immunostaining for HSP 72 in the OHCs reached a plateau level at 3 h, which was maintained until 12 h after injection. The amount of immunoreactive OHCs in the 20 mg/kg group was smaller than those in 5 and 10 mg/kg groups and declined after 6 h. The bands for HSP 72 became less intense as the cisplatin dosage increased from 5 to 10 and 20 mg/kg in Western blotting. The change in ABR threshold was small in the 5 and 10 mg/kg groups and a marked change in threshold was observed in the 20 mg/kg group. Detection of HSP 72 after cisplatin injection could confirm the OHCs as one of the major injured cells in the cochlea. With a lethal dosage of cisplatin (20 mg/kg), HSP 72 expression was less prominent and declined after 6 h.