Association Between Serum Vitamin D Level and Ménière's Disease.

OBJECTIVES: Ménière's disease (MD) is a well-known inner ear disease; however, the etiopathogenesis is unknown. Several factors may be involved. Meanwhile, vitamin D is reported to have an important role in inner ear physiology. The aim of this study is to evaluate the relation between vitamin D deficiency and MD. STUDY DESIGN: This matched case-control study compared serum vitamin D levels between patients with definite MD and those without it. SETTING: The study was done between August 2018 and December 2019 at Ghaem University Hospital in Mashhad, Iran. METHODS: Twenty-eight patients with definite MD were matched with a group of 84 healthy individuals, regarding age, sex, body mass index, and occupation (indoor vs outdoor). The serum level of vitamin D (25-hydroxyvitamin D3) was measured in both groups. RESULTS: The mean ± SD vitamin D level was 18.9 ± 9.7 ng/mL in the case group and 25.2 ± 13.7 ng/mL in the control group (P = .027). There was a significant difference between the case and control groups according to the results of the conditional logistic regression model (P = .03; adjusted odds ratio, 0.96). In the MD group, 17 (60.7%) patients were vitamin D deficient, 6 (21.4%) insufficient, and only 5 (17.9%) sufficient. CONCLUSIONS: The results of this study show that serum vitamin D level in MD is significantly lower than that of the control group. However, the role of vitamin D supplementation in the management of MD needs further study. LEVEL OF EVIDENCE: 4.

Correlation between auditory-vestibular functions and estrogen levels in postmenopausal patients with Meniere's disease.

BACKGROUND: To investigate auditory and vestibular functions, estrogen levels, and its clinical correlation in postmenopausal females with Meniere's disease (MD). METHODS: We retrospectively analyzed the serum estradiol (E2) levels and the auditory and vestibular functions measured by auditory brainstem response (ABR) to high click rate, pure-tone audiometry (PTA), and caloric test on postmenopausal women who suffered from MD or not at the Specialist Clinic of Vertigo, Shandong Provincial Hospital, during September 2010 to October 2014. RESULTS: A total of 76 postmenopausal patients with MD and 50 healthy postmenopausal controls were included. The patients with MD had lower estrogen levels (22.50 ± 16.66 pg/mL vs 30.69 ± 18.59 pg/mL, P = 0.011), longer I-V interpeak latency of ABR (left 0.22 ± 0.16 mseconds vs 0.18 ± 0.10 mseconds, P = 0.118; right 0.24 ± 0.13 mseconds vs 0.17 ± 0.09 mseconds, P = 0.001), and higher unilateral weakness (UW) value (P < 0.001) in comparison with the controls. The mean pure-tone thresholds of at the speech frequency (500 Hz, 1 kHz, 2 kHz, and 3 kHz) were significantly elevated in patients with MD than those in the controls (left P < 0.001, right P < 0.01). The estradiol level of patients with MD was correlated with ABR latency (left r = -0.229, P < 0.05; right r = -0.220, P < 0.05) and UW value (r = -0.328, P < 0.05), but not with mean pure-tone threshold. CONCLUSIONS: Estrogen levels correlated with auditory and vestibular function in postmenopausal patients with MD. Low estrogen may be involved in the microcirculatory disturbance of the inner ear, affecting the occurrence and development of MD.

Ménière's disease with unremitting floating sensation is associated with canal paresis, gravity-sensitive dysfunction, mental illness, and bilaterality.

OBJECTIVE: The aim of the present study was to evaluate the association of neuro-otological examination, blood tests, and scoring questionnaire data with treatment-resistant intractability of persistent dizziness in Ménière's disease. METHODS: We managed 1520 successive vertigo/dizziness patients at the Vertigo/Dizziness Center in Nara Medical University from May 2014 to April 2018. Five hundred and twenty-two patients were diagnosed with Ménière's disease (522/1520; 34.3%) according to the 2015 diagnostic guideline of the International Classification of Vestibular Disorders. Among the patients with Ménière's disease there were 102 with intractable rotatory vertigo attacks for more than 3-6 months (102/522; 19.5%), including 20 bilateral cases (20/102; 19.6%), and 88 with intractable unremitting floating sensation rather than rotatory vertigo attacks for more than 3-6 months (88/522; 16.9%), including 28 bilateral cases (28/88; 31.8%). Sixty out of 88 cases with intractable unremitting floating sensation were unilateral and were enrolled for hospitalization to undergo neuro-otological examinations including pure-tone audiometry (PTA), the caloric test (C-test), vestibular evoked cervical myogenic potentials (cVEMP), subjective visual vertical (SVV) test, glycerol test (G-test), electrocochleogram (ECoG), inner ear magnetic resonance imaging (ieMRI), blood tests including anti-diuretic hormone (ADH) and bone alkaline phosphatase (BAP), and self-rating questionnaires of depression score (SDS). Data are presented as positive (+) ratios of the number of patients with examination and questionnaire data outside of the normal range. RESULTS: The ratios (+) were as follows: C-test=33.3% (20/60), cVEMP=25.0% (15/60), SVV=50.0% (30/60), G-test=55.0% (33/60), ECoG=63.3% (38/60), ieMRI=86.7% (52/60), ADH=35.0% (21/60), BAP=11.7% (7/60), and SDS=40.0% (24/60). Multivariate regression analysis revealed that the periods of persistent dizziness were significantly longer in unilateral Ménière's patients with C-test(+), SVV(+), and SDS(+) compared with those with negative findings. Additionally, the periods in bilateral cases were significantly longer than those in unilateral ones. CONCLUSIONS: Although approximately 70% of patients with Ménière's disease are usually treatable through the appropriate conservative medical therapy, the presence of canal paresis, gravity-sensitive dysfunction, neurosis/depression, and bilaterality may make the persistent dizziness intractable and may thus require additional treatments.

Nutritional Mushroom Treatment in Meniere's Disease with Coriolus versicolor: A Rationale for Therapeutic Intervention in Neuroinflammation and Antineurodegeneration.

Meniere's disease (MD) represents a clinical syndrome characterized by episodes of spontaneous vertigo, associated with fluctuating, low to medium frequencies sensorineural hearing loss (SNHL), tinnitus, and aural fullness affecting one or both ears. To date, the cause of MD remains substantially unknown, despite increasing evidence suggesting that oxidative stress and neuroinflammation may be central to the development of endolymphatic hydrops and consequent otholitic degeneration and displacement in the reuniting duct, thus originating the otolithic crisis from vestibular otolithic organs utricle or saccule. As a starting point to withstand pathological consequences, cellular pathways conferring protection against oxidative stress, such as vitagenes, are also induced, but at a level not sufficient to prevent full neuroprotection, which can be reinforced by exogenous nutritional approaches. One emerging strategy is supplementation with mushrooms. Mushroom preparations, used in traditional medicine for thousands of years, are endowed with various biological actions, including antioxidant, immunostimulatory, hepatoprotective, anticancer, as well as antiviral effects. For example, therapeutic polysaccharopeptides obtained from Coriolus versicolor are commercially well established. In this study, we examined the hypothesis that neurotoxic insult represents a critical primary mediator operating in MD pathogenesis, reflected by quantitative increases of markers of oxidative stress and cellular stress response in the peripheral blood of MD patients. We evaluated systemic oxidative stress and cellular stress response in MD patients in the absence and in the presence of treatment with a biomass preparation from Coriolus. Systemic oxidative stress was estimated by measuring, in plasma, protein carbonyls, hydroxynonenals (HNE), and ultraweak luminescence, as well as by lipidomics analysis of active biolipids, such as lipoxin A4 and F2-isoprostanes, whereas in lymphocytes we determined heat shock proteins 70 (Hsp72), heme oxygenase-1 (HO-1), thioredoxin (Trx), and γ-GC liase to evaluate the systemic cellular stress response. Increased levels of carbonyls, HNE, luminescence, and F2-isoprostanes were found in MD patients with respect to the MD plus Coriolus-treated group. This was paralleled by a significant (p < 0.01) induction, after Coriolus treatment, of vitagenes such as HO-1, Hsp70, Trx, sirtuin-1, and γ-GC liase in lymphocyte and by a significant (p < 0.05) increase in the plasma ratio-reduced glutathione (GSH) vs. oxidized glutathione (GSSG). In conclusion, patients affected by MD are under conditions of systemic oxidative stress, and the induction of vitagenes after mushroom supplementation indicates a maintained response to counteract intracellular pro-oxidant status. The present study also highlights the importance of investigating MD as a convenient model of cochlear neurodegenerative disease. Thus, searching innovative and more potent inducers of the vitagene system can allow the development of pharmacological strategies capable of enhancing the intrinsic reserve of vulnerable neurons, such as ganglion cells to maximize antidegenerative stress responses and thus providing neuroprotection.

Association of Ménière disease with human leukocyte antigen in Taiwanese population.

The etiology of Ménière disease (MD) is multifactorial; genetic factors seem to play an important role. The associations between MD and human leukocyte antigen (HLA) status have been studied previously in several populations and have shown that the HLA alleles imparting susceptibility varied. In the present study, we explored HLA status in Taiwanese patients with definitive MD. HLA was typed via polymerase chain reaction, sequence-specific oligonucleotide genotyping in 35 patients with MD diagnosed using the criteria of the American Academy of Otolaryngology-Head and Neck Surgery and 70 unrelated healthy controls. HLA allele association tests were used to evaluate differences in allelic frequencies between the patients and controls. The allelic frequency of HLA-A*11 was significantly greater in MD patients than in controls (52.9 vs. 31.4%, odds ratio: 2.45, 95% confidence interval: 1.4 to 4.4, p = 0.004, p corrected = 0.03). Thus, A*11 may be a useful HLA biomarker in Taiwanese patients with MD. Further larger-scale studies are required.

A Mysterious Role of Arginine Vasopressin Levels in Ménière's Disease-Meta-analysis of Clinical Studies.

OBJECTIVE: There are contradicting claims that patients with Ménière's disease (MD) have elevated levels of arginine vasopressin (AVP). The results of published studies regarding the difference of AVP level between MD patients and non-MD control subjects are inconsistent. We propose that the discrepancy of AVP levels during different MD phases may be a potential reason. Thus, we conducted a meta-analysis to analyze the precise estimate of this hypothesis. DATA SOURCES: PubMed, Medline, and Cochrane databases from the earliest publication, up until September 2016; references from meta-analyses and related review articles. STUDY SELECTION AND DATA EXTRACTION: Clinical studies that reported AVP level in MD patients and non-MD controls were independently reviewed according to the inclusion criteria. The Newcastle-Ottawa Scale was used to assess quality of studies. DATA SYNTHESIS: Random effects model was used to calculate the weighted mean difference. CONCLUSION: Eight studies met the inclusion criteria. AVP levels of MD patients in acute phase (WMD = 2.29, 95% CI = 0.84-3.74, Z = 3.10, p = 0.002) were significantly higher than non-MD subjects. For MD patients in remission phase the difference of AVP levels between the MD patients and the non-MD controls was found (WMD = 0.54, 95% CI = -0.06 to 1.02, Z = 2.20, p = 0.03). However, AVP level was not an ideal biomarker of MD patients. Regardless of MD phase, there were no significant differences in the AVP level of MD patients (WMD = 0.27, 95% CI = -0.10 to 0.64, Z = 1.43, p = 0.15). Future investigations with larger sample sizes are needed to verify the results.

Dehydration effects of a V2 antagonist on endolymphatic hydrops in guinea pigs.

We investigated the influence of vasopressin type 2 receptor antagonist (OPC-41061; Tolvaptan) on experimentally induced endolymphatic hydrops (EH) in guinea pigs. In the first series, the endolymphatic sac (ES) of the left ear of all animals was electrocauterized. Four weeks after surgery, the animals were allocated to four groups: three systemic applications groups (saline, OPC 10 and 100 mg/kg) and a local round window (RW) OPC 1 mg/body application group. We examined the histopathology of the temporal bones and assessed volumetric changes of the endolymphatic space in the cochlea and saccule. In the second series, we investigated the effects of systemic and topical applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM). In the first series, we found that EH was reduced in the OPC 10 mg/kg systemic and OPC RW application groups. In contrast, EH increased in the OPC 100 mg/kg systemic application group. In the second series, neither p-VP levels nor p-OSM were significantly different among the non-OPC, OPC 10 mg/kg systemic, and OPC RW application groups. However, in the OPC 100 mg/kg systemic application group, the p-VP level was significantly higher than that in other groups, and p-OSM was higher than that in the non-OPC group. The systemic application of a low dose of OPC and topical application of OPC resulted in reduced EH in the face of minimal systemic effects (p-VP and p-OSM). These findings suggest that OPC-41061 may be one useful treatment option for EH.

Altered chromogranin A circulating levels in Meniere's disease.

OBJECTIVES: Meniere's disease (MD) is an inner ear disorder characterized by episodic vertigo, ear fullness, and hearing loss; usually vertigo attacks cluster in specific period. We studied in MD patients the circulating levels of chromogranin A (CgA) and vasostatin-1 (VS-1), secreted by the neuroendocrine system and involved in the regulation of the endothelial barrier function. METHODS: Serum levels were assessed in 37 MD patients and 36 controls. The ratio between VS-1 and CgA was calculated. RESULTS: CgA was increased in patients compared to controls (1.46 versus 0.67 nM, p = 0.01) while no difference was detected for VS-1 (0.41 versus 0.39, resp.). CgA levels in patients positively correlated with the frequency of vertigo spells in the previous four weeks (p = 0.008) and negatively with the time in days from the last vertigo attack (p = 0.018). Furthermore, the VS-1/CgA ratio negatively correlated with the frequency of vertigo spells (p = 0.029) and positively correlated with the time from the last attack (p = 0.003). CONCLUSION: The results indicate that variations of CgA levels, but not of VS-1, occur in the blood of patients with active MD, depending on the frequency of vertigo spells and the time from the last crisis.

Autoimmunity as a candidate for the etiopathogenesis of Meniere's disease: detection of autoimmune reactions and diagnostic biomarker candidate.

Meniere's disease is an inner ear disorder that can manifest as fluctuating vertigo, sensorineural hearing loss, tinnitus, and aural fullness. However, the pathologic mechanism of Meniere's disease is still unclear. In this study, we evaluated autoimmunity as a potential cause of Meniere's disease. In addition we tried to find useful biomarker candidates for diagnosis. We investigated the protein composition of human inner ear fluid using liquid column mass spectrometry, the autoimmune reaction between circulating autoantibodies in patient serum and multiple antigens using the Protoarray system, the immune reaction between patient serum and mouse inner ear tissues using western blot analysis. Nine proteins, including immunoglobulin and its variants and interferon regulatory factor 7, were found only in the inner ear fluid of patients with Meniere's disease. Enhanced immune reactions with 18 candidate antigens were detected in patients with Meniere's disease in Protoarray analysis; levels of 8 of these antigens were more than 10-fold higher in patients than in controls. Antigen-antibody reactions between mouse inner ear proteins with molecular weights of 23-48 kDa and 63-75 kDa and patient sera were detected in 8 patients. These findings suggest that autoimmunity could be one of the pathologic mechanisms behind Meniere's disease. Multiple autoantibodies and antigens may be involved in the autoimmune reaction. Specific antigens that caused immune reactions with patient's serum in Protoarray analysis can be candidates for the diagnostic biomarkers of Meniere's disease.

A proteomics-driven assay defines specific plasma protein signatures in different stages of Ménière's disease.

Ménière's disease (MD) is a common disorder of the inner ear whose hallmarks are vertigo, tinnitus, aural fullness, and progressive hearing loss. The degree of severity of the disease is quite heterogeneous, and so is its pathogenesis. A multifactorial inheritance of intrinsic and extrinsic factors has been described, but there is not a common agreement on the molecular basis of MD. In a recent article, we have demonstrated that patients suffering from MD share a common plasma proteomic signature, characterized by the presence of several up- and down-regulated proteins. In this study, we have further extended our analysis and show that the differential expression of plasma proteins can identify specific subsets of MD-affected individuals, depending on their stage. Our findings confirm our plasma proteomics-driven approach as a powerful tool for early diagnosis of MD and uncover a potentially starring role for some proteins in the development and fate of this frustrating disease, whose pathogenesis still remains unclear.

The relationship of homocysteine, vitamin B12, folic acid levels with vertigo.

OBJECTIVES: In this study the relationship of serum homocysteine, vitamin B12, folic acid levels and peripheral vestibular dysfunction (PVD) was investigated. PATIENTS AND METHODS: Forty-one patients (31 females, 10 males; mean age 57.34±14.3 years; range 12 to 80 years) who admitted to Baskent University Hospital Ear Nose and Throat Department between the dates of April 2005 - December 2007 with complaint of vertigo were prospectively analyzed and diagnosed using audio-vestibular test, at the same time serum homocysteine, vitamin B12, folic acid measurements was done from the blood samples of patients. The patients were divided into three groups as Meniere's disease, vestibular neurinitis, and benign paroxismal positional vertigo (BPPV) according to the diagnoses and serum homocysteine, vitamin B12, folic acid levels of patients were compared to normal values in and between groups. RESULTS: Of the patients, 29.3% (n=12) were diagnosed with Meniere's disease, 36.6% (n=15) with vestibular neurinitis, and 34.1% (n=14) with BPPV. Serum homocysteine leves of patients were 12.42±3.56 umol/L, 11.32±4.14 umol/L and 10.72±2.95 umol/L (p>0.05) in Meniere's disease, vestibular neurinitis, and BPPV respectively; vitamin B12 levels were 371.58±141.35 pg/ml, 288.13±139.51 pg/ml, 352.14±150.41 pg/ml (p>0.05) respectively and folic acid levels were 8.76±3.2 umol/L, 10.63±6.59 umol/L, 8.8±3.18 umol/L (p>0.05) respectively. The values were similar in all patients. No statistically significant difference was found in and between groups comparing with normal values. CONCLUSION: This is the first prospective study investigating the relationship of serum homocystein, vitamin B12 and folic acid levels with PVD. We found that there is no relationship of homocysteine, vitamin B12, folic acid levels with PVD.

Effect of thirst challenge on ADH levels in patients with bilateral Menière's disease.

The aim of the study was to investigate plasma ADH levels and plasma/urine osmolality in patients suffering from bilateral Menière's disease since a disturbance in the water household after thirst challenge is a suspected pathogenic factor in the development of this disease. In this study the plasma ADH levels and plasma/urine osmolality of bilateral Menière's disease patients under thirst challenge were investigated to show whether the water balance is affected. 9 patients with bilateral Menière's disease and 9 healthy controls skipped water intake for 12 h. Plasma ADH, plasma/urine osmolality, and electrolytes were measured after this thirst period as well as 8 h later after food and fluid intake. During food and fluid intake the patients demonstrated a slightly higher plasma ADH level and plasma osmolality than controls, whereas at the end of the thirst period patients and the controls showed no significant change. Instead the urine osmolality differed significantly (p<0.001): showing a high urine osmolality in controls and an almost stable urine osmolality in patients after thirst challenge. This indicates that the water balance in patients is likely different from that of controls. These observations point to ADH and its target aquaporine 2 as keyplayers in the pathophysiological events leading to the development of Menière's disease.

Proteomics in Ménière disease.

Ménière's disease (MD) is a disorder of the inner ear characterized by an insidious onset and aspecific symptoms, such as dizziness, vertigo, tinnitus, and hearing loss, that may become very debilitating. The presence of endolymphatic hydrops is a common feature in MD patients, but the pathophysiology is still largely unknown. In this study, we have used a proteomics-driven approach to identify potential biomarkers of MD. To this end, plasma was obtained from whole blood of 16 individuals previously diagnosed as suffering from MD and compared to plasma from healthy donors. A depletion of the highly abundant proteins (i.e., albumin, IgG, transferrin, etc.) was performed in order to enhance the chance of detection of the less represented ones, therefore reducing the noise-background. Two-dimensional gel electrophoresis, followed by in-gel tryptic digestion of the selected spots and LC-MS/MS analysis, allowed us to identify a set of proteins whose expression appears to be differentially modulated in patients versus controls. In particular: complement factor H and B, fibrinogen alpha and gamma chains, beta-actin and pigment epithelium derived factor are over expressed; on the other hand, the levels of beta-2 glycoprotein-1, vitamin D binding protein and apolipoprotein-1 are significantly decreased in the plasma of MD-affected individuals. Even though preliminary and not necessarily linked directly to the molecular pathogenesis of the disease, our original findings suggest that a molecular signature, represented by the plasma protein profile previously described, might represent a potentially powerful, innovative and not invasive tool for early diagnosis and clinical management of MD patients. J. Cell. Physiol. 227: 308-312, 2012. © 2011 Wiley Periodicals, Inc.

High prevalence of systemic autoimmune diseases in patients with Menière's disease.

BACKGROUND: Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL). METHODS AND FINDINGS: We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ). The observed prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively). Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007). There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD. CONCLUSIONS: Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD.

The relevance of hypothalamus-pituitary-adrenocortical axis-related hormones to the cochlear symptoms in Ménière's disease.

OBJECTIVE: To investigate the association of the HPA (hypothalamus-pituitary-adrenocortical) axis-related hormones with the progression of cochlear symptoms in patients with Ménière's disease. DESIGN: Clinical assessments (Tinnitus Handicap Inventory: THI, visual analog scale to rate the degree of the tinnitus: VAS, hearing levels in pure-tone audiometry) were conducted upon entry into the study (baseline) and at 12 weeks follow-up (week 12). Blood sampling to measure HPA axis-related hormones took place between 9:00 and 10:00 a.m. at baseline and at 12 weeks follow-up. STUDY SAMPLES: This study consisted of 20 unilateral Ménière's disease patients and 21 patients with other diseases with unilateral sensorineural hearing loss and tinnitus. RESULTS: A significant deterioration of the hearing level at high frequency range, especially at 2 kHz, was found during the 12 weeks follow-up in the Ménière's disease group (p < 0.05). The average hearing levels significantly correlated with the serum cortisol level at baseline and week 12 in the Ménière's disease group, especially regarding the high frequency levels (p < 0.01). CONCLUSIONS: Our results suggest that the cortisol levels influence the endolymphatic homeostasis resulting in a deterioration of hearing at high frequency with upstaging of Ménière's disease.

Polymorphisms of CD16A and CD32 Fcγ receptors and circulating immune complexes in Ménière's disease: a case-control study.

BACKGROUND: Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC. We examined single-nucleotide polymorphism (SNPs) in the CD16A and CD32 genes in patients with MD which may determine a Fcγ receptor with lower binding to CIC. METHODS: The functional CD16A (FcγRIIIa*559A > C, rs396991) and CD32A (FcγRIIa*519A > G, rs1801274) SNPs were analyzed using PCR-based TaqMan Genotyping Assay in two cohorts of 156 mediterranean and 112 Galicia patients in a case-control study. Data were analyzed by χ2 with Fisher's exact test and Cochran-Armitage trend test (CATT). CIC were measured by ELISA for C1q-binding CIC. RESULTS: Elevated CIC were found in 7% of patients with MD during the intercrisis period. No differences were found in the allelic frequency for rs396991 or rs1801274 in controls subjects when they were compared with patients with MD from the same geographic area. However, the frequency of AA and AC genotypes of CD16A (rs396991) differed among mediterranean and Galicia controls (Fisher's test, corrected p = 6.9 × 10-4 for AA; corrected p = 0.02 for AC). Although genotype AC of the CD16A receptor was significantly more frequent in mediterranean controls than in patients, [Fisher's test corrected p = 0.02; OR = 0.63 (0.44-0.91)], a genetic additive effect for the allele C was not observed (CATT, p = 0.23). Moreover, no differences were found in genotype frequencies for rs396991 between patients with MD and controls from Galicia (CATT, p = 0.14). The allelic frequency of CD32 (rs1801274) was not different between patients and controls either in mediterranean (p = 0.51) or Galicia population (p = 0.11). CONCLUSIONS: Elevated CIC are not found in most of patients with MD. Functional polymorphisms of CD16A and CD32 genes are not associated with onset of MD.

The association of the plasma vasopressin level during attacks with a prognosis of Meniere's disease.

An elevation of the plasma arginine vasopressin (AVP) level has frequently been observed in Meniere's disease patients. However, little is known regarding the mechanism behind this elevation. The plasma AVP levels in acute phase were determined in 21 Meniere's disease patients and 16 patients with other types of vertigo. The plasma AVP levels of Meniere's disease patients in the acute phase were significantly higher than in those of other vertigo patients (p < 0.01). In Meniere's disease patients with abnormally high levels of AVP (more than 3.5 pg/ml) in the acute phase, 36% of patients were resistant to conservative treatments for frequent vertigo attacks for the follow-up period of at least 2years. A significant correlation was observed between the plasma AVP in the acute phase and the highest hearing threshold level at a frequency of 1kHz for the follow-up period of at least 1 year (r=0.45, p < 0.05). These results suggest that the elevation in plasma AVP level in the acute phase is associated with the prognosis of Meniere's disease.

Elevated antithyroid peroxidase and antinuclear autoantibody titers in Ménière's disease patients: more than a chance association?

OBJECTIVE/HYPOTHESIS: The aim of this prospective study is to evaluate the possible association between Ménière's disease (MD) and autoantibodies. METHODS: Fifty-five patients with definite MD (51 unilateral and 4 bilateral) were matched with 55 patients with unilateral vestibular paresis without cochlear involvement and 55 healthy subjects. Blood samples were collected from all study subjects for the determination of serum TSH, free triiodothyronine, free thyroxine, anti-TSH receptor antibody, antithyroperoxidase antibody, antithyroglobulin antibody and of antibodies to non-organ-specific antigens, namely antinuclear antibodies, antibodies to extractable nuclear antigens and antineutrophilic cytoplasmic antibodies. RESULTS: Thirty-three subjects (60%) of the MD group had 1 or more elevated serum autoantibody levels, both organ and non-organ specific; 16 patients (29.1%) with unilateral vestibular paresis had 1 or more elevated serum autoantibody levels, while 13 healthy subjects (23.6%) had 1 or more elevated serum autoantibody levels. CONCLUSIONS: Based on our data we speculate that there is a more than a chance association between MD and 'autoimmunity', thus suggesting a hypothetical role of the immune system in MD pathogenesis. In other words, a pathogenetic role of an 'immune dysregulation' in MD patients can be hypothesized.

Endogenous ouabain in Ménière's disease.

OBJECTIVE: Endogenous Ouabain (EO) has been demonstrated to modulate the activity of Na+, K+ -ATPase. Our purpose was to measure plasma levels of EO in Ménière's Disease (MD) subjects as a possible predisposing factor to developing and maintaining hydrops. STUDY DESIGN: Case-control study. SETTINGS: University hospital. PATIENTS: Thirty-nine MD subjects and 29 controls with a lifetime negative history for vertigo and dizziness. MAIN OUTCOME MEASURES: Plasma levels of EO. RESULTS: Plasma EO in MD subjects was in the range between 33 and 504 pmol/L (median, 135.5 pmol/L), whereas in the control group, plasma EO varied between 70 and 724 pmol/L (median, 205 pmol/L). The Mann-Whitney U test detected a statistically significant difference (p = 0.0001). CONCLUSION: Low plasma levels of EO have been proposed to augment Na-K pump activity, whereas high EO levels show an inhibitory effect on the pump activity. A proper pump activity may be necessary to keep the right ionic amount and osmolarity in endolymph. Although other possibilities may be considered, we suggest that altered control mechanisms of pump activity may be related to the pathogenesis and maintenance of MD.