Effects of salicylate on the inflammatory genes expression and synaptic ultrastructure in the cochlear nucleus of rats.

Aspirin (salicylate), as a common drug that is frequently used for long-term treatment in a clinical setting, has the potential to cause reversible tinnitus. However, few reports have examined the inflammatory cytokines expression and alteration of synaptic ultrastructure in the cochlear nucleus (CN) in a rat model of tinnitus. The tinnitus-like behavior of rats were detected by the gap prepulse inhibition of acoustic startle (GPIAS) paradigm. We investigated the expression levels of the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), N-methyl D-aspartate receptor subunit 2A (NR2A) mRNA and protein in the CN and compared synapses ultrastructure in the CN of tinnitus rats with normal ones. GPIAS showed that rats with long-term administration of salicylate were experiencing tinnitus, and the mRNA and protein expression levels of TNF-α and NR2A were up-regulated in chronic treatment groups, and they returned to baseline 14 days after cessation of treatment. Furthermore, compared to normal rats, repetitive salicylate-treated rats showed a greater number of presynaptic vesicles, thicker and longer postsynaptic densities, increased synaptic interface curvature. These data revealed that chronic salicylate administration markedly, but reversibly, induces tinnitus possibly via augmentation of the expression of TNF-α and NR2A and cause changes in synaptic ultrastructure in the CN. Long-term administration of salicylate causes neural plasticity changes at the CN level.

Prevalence and clinical significance of anticardiolipin, anti-beta2-glycoprotein-1, and anti-heat shock protein-70 autoantibodies in sudden sensorineural hearing loss.

Sudden sensorineural hearing loss (SSNHL) is frequently classified as 'idiopathic' since the causative factor responsible for its onset is not identified in most cases. In the present study, we determined whether SSNHL is clinically associated with serum anti-heat shock protein-70 (anti-HSP70) and antiphospholipids (anti-PLs) autoantibodies and whether these autoantibodies have an impact on the prognosis of SSNHL. Sera from 63 patients with SSNHL were screened prospectively for the presence of anti-HSP70 and anti-PLs autoantibodies by an enzyme-linked immunosorbent assay test. Anti-PLs antibodies in this study consisted of anticardiolipin, and anti-beta(2)-glycoprotein-1 antibodies. Serum was assayed for anti-HSP70 IgG antibodies using recombinant human HSP70. Demographic, clinical, and audiometric variables were analyzed to find the possible role of serum autoantibodies in SSNHL patients. Sixteen patients (25.4%) had demonstrable anti-HSP70 antibodies in serum. Twenty-one patients (33.3%) showed a positive result for at least one isotype (IgM or IgG) of anti-PLs. In 19% of the patients, anti-HSP70 and anti-PLs antibodies were positive in two combinations. A statistically significant association was found between anti-HSP70 antibodies and the Siegel recovery grade subgroup. SSNHL patients who were positive for anti-HSP70 antibodies showed a significantly higher rate of complete recovery and incomplete but partial recovery than SSNHL patients without anti-HSP70 antibodies (p = 0.0496). Statistically significant association was found between total anticardiolipin, total anti-beta(2)-glycoprotein-1, total anti-PLs, and anti-PLs in combination with anti-HSP70 antibodies and age (p = 0.0229). The detection of autoantibodies to HSP70 and PLs offers a pliable explanation for the immune-mediated mechanism of SSNHL. The present study confirms and supports previous studies regarding the association between anti-HSP70 and anti-PLs antibodies with SSNHL, and is the first to identify a positive association between anti-HSP70 antibodies and a positive outcome of SSNHL. Further studies are necessary in order to identify and further clarify the immunologic role of the presence of autoantibodies and their impact on the prognosis of SSNHL.

Tinnitus and Coxsackie B infections: a case series.

Tinnitus is a frequent and often debilitating condition. There is consensus in the scientific community that there exist various forms of tinnitus, which differ in their pathogenesis. Here we report a series of five cases where the onset of tinnitus was associated with viral infections. In all five patients elevated antibodies against Coxsackie B have been detected. This observation suggests that Coxsackie B Virus infections might be involved in the development of some cases of tinnitus and indicate that further systematic investigations are warranted.

Psychological, neural, endocrine, and immune study of stress in tinnitus patients: any correlation between psychometric and biochemical measures?

OBJECTIVES: The present study was carried out in tinnitus patients in order to study the psychological distress and the biochemical measures of this stressful condition. Psychological features were compared to immune and neuroendocrine parameters in order to verify in these subjects the possible presence of psychological and somatic responses to stress. METHODS: We studied 85 tinnitus patients who underwent hematochemical immune tests: lymphocyte subpopulations (CD3; CD4; CD3+CD4; CD8; CD19; CD16NK; CD3+CD16+CD56; and CD4/CD8), cortisol, adrenocorticotropic hormone, beta-endorphin, prolactin, and urinary catecholamine. RESULTS: Clinically, significant scores were obtained for hysteria, depression, paranoia, hypochondrias, and social introversion; and high scores were obtained for anxiety, depression, care for health, difficulty of treatment, low self-esteem, family and work difficulties, and social discomfort. There was a low to medium level of self-perception of stress. The less a subject felt stressed, the higher was his or her satisfaction level in the areas of psychological and physical functioning. The scores on the tests and the biochemical measures did not show a significant correlation, but there was a tendency to correlation for the lymphocytes CD19 and CD16NK and for adrenocorticotropic hormone. CONCLUSIONS: The comparison between the psychometric and biochemical variables did not reveal any significant correlation among stress perception, daily satisfaction, and the biochemical parameters of stress.

Western blot immunoassay for HSP-70 antibodies in idiopathic tinnitus: a preliminary report.

OBJECTIVES: Our preliminary study investigated the role of nonspecific immunologic tests and immunoassay for heat shock protein 70 (HSP-70) in supporting the possibility of an autoimmune inner ear process determining idiopathic tinnitus. METHODS: Thirty-six consecutive patients with idiopathic tinnitus without other otologic or autoimmune diseases and 20 healthy blood donor subjects underwent determinations of circulating immune complexes (CICs) and other nonspecific immunologic factors and immunoassay for HSP-70. RESULTS: The mean CIC values were 4.2 microg/mL in the tinnitus patients and 0.9 microg/mL in the control group (p = .012). Thirteen of the 36 tinnitus patients and none of the control group were HSP-70-positive. Ten of the 13 HSP-70-positive patients had CIC values higher than normal. In the tinnitus group, the mean CIC values were 6.9 microg/mL and 2.6 microg/mL in the HSP-70-positive and -negative subgroups, respectively (p = .024). CONCLUSIONS: It may be hypothesized that in a significant number of cases, idiopathic tinnitus could be induced by immune response to inner ear-specific HSP-70.

Impact of a relaxation training on psychometric and immunologic parameters in tinnitus sufferers.

OBJECTIVE: Tinnitus often entails severe psychological distress. Reversely, tinnitus may be considered as a chronic stressor. Based on this hypothesis, we investigated whether improving stress-managing capabilities would influence psychological and stress-related immunological parameters in chronic tinnitus sufferers. METHODS: Tinnitus (TPs, n=26) and non-tinnitus participants (NTPs, n=13) took part in a standardised 10-week relaxation program. An additional group of tinnitus sufferers (n=18), randomly assigned to a waiting list, served as control (TC) subjects. Mood, perceived stress, global quality of life, and tinnitus disturbance were assessed before and after the intervention. The stress-sensitive immunological parameters TNF-alpha, IL-6, and IL-10 were measured before, during, and at the end of the intervention. RESULTS: The program resulted in a significantly decreased perception of stress, anxious depression, anger, and tinnitus disturbance, paralleled by a reduction of TNF-alpha. No alterations were noted for IL-6 or IL-10. For the NTPs and TCs, no relevant psychological or immune changes could be observed. CONCLUSION: The data suggest that (1) the training offered improved stress-managing capabilities in chronic tinnitus sufferers, and (2) TNF-alpha may be conceived as a stress marker.

Cogan's syndrome: clinical significance of antibodies against the inner ear and cornea.

The aim of this study was to evaluate the pathological significance of antibodies against cornea and inner ear tissue in the development of audiovestibular and ocular symptoms in patients with Cogan's syndrome (CS). We analysed the serum of 5 CS patients for binding of IgM and IgG to fresh cryosections of rat labyrinth (semicircular canals, ampulla, utricle, saccule) and cornea by indirect immunofluorescence (IF). The predominant pattern of anti-corneal IgM was staining of the superficial cell layer of the non-keratinizing squamous epithelium. IgM against cornea was found in 3 patients, all of whom had bilateral inflammatory eye signs at the start of the disease. However, IgM was also detected in the chronic stage of the disease when no clinical signs of eye involvement were apparent. The study includes the first follow-up examination of anti-corneal IgM and IgG antibodies during a complete episode of active CS. During the first episode of CS in 1 patient, anti-corneal IgM became detectable 1 week after the onset of interstitial keratitis and 3 weeks after the onset of audiovestibular symptoms. It increased over several weeks and then fell to very low levels. However, at no time was anti-corneal IgG found. In the course of follow-up examinations, the serum of 4 patients intermittently contained low titre IgG antibodies against inner ear labyrinthine tissue, but without any clear correlation with the active stages of CS. In addition, high-resolution MRI (HR-MRI) of the inner ear was performed in the acute and chronic stages of CS to evaluate the activity of CS. In the acute stage, HR-MRI revealed abnormal MRI signals in the vestibule, semicircular canals, vestibular nerve, or cochlea. In the chronic stage, patients showed narrowing or occlusion of semicircular canals and the cochlea on the 3D-CISS images, but no high signal lesions (T1) and no enhancement. Antibodies against cornea or labyrinthine tissue were not consistently detected in CS and the level of organ-specific antibodies did not correlate with the activity of the disease.

Allergy for the otologist. External canal to inner ear.

Allergy may affect the outer, the middle, or the inner ear. Although the otologic manifestations of allergy are not by themselves diagnostic, the history, including family history and associated symptoms in other target organs, will often help lead to the correct diagnosis and institution of therapy. Patients with significant and chronic symptoms, including those with labyrinthine symptoms of allergy, will respond well to specific immunotherapy and/or dietary elimination.

Antibodies against inner-ear proteins in the sera of patients with inner-ear diseases.

Sera from patients with various inner-ear diseases, especially Ménière's disease, were investigated by Western blot against guinea pig inner-ear proteins. Of 45 patients, 24 (53%) with various inner-ear diseases had antibodies against inner-ear proteins, compared with 0 of 10 (0%) in control subjects without inner-ear diseases. Of the 10 proteins that showed a positive reaction with patient sera, the 28-kD band was unique in that it appeared only in the membranous fraction of the inner ear and was highly positive (28%) in reaction with Ménière's disease patient sera. The results in the present study with proteins extracted from guinea pig inner ear were consistent with our previous study using proteins from human inner ear, suggesting that the 28-kD protein may be a candidate for detecting autoimmune inner-ear disease.

Use of a screening RAST in a large neuro-otologic practice.

Evidence in the literature emphasizes the role of the immune system in disorders of the inner ear and eustachian tube. We initially investigated the presence of inhalant allergy in selected patients seen for otologic problems by means of a screening radioallergosorbent test (RAST), using either a microscreen or a limited antigen panel. This study analyzed the results of tests performed over a 2-year period on 186 patients seen by one of us (WLM) for treatment of vertigo (66%), tinnitus (63%), hearing loss (49%), aural fullness (48%), Meniere's quadrad (27%), balance disturbance other than true vertigo (21%), and eustachian tube dysfunction (4%). We found an incidence of immunoglobulin E-mediated hypersensitivity of nearly 40% in a patient population selected solely for neuro-otologic symptoms and not for sinonasal symptoms. This figure is more than double that quoted for the general population. We also found a surprisingly high incidence of mold antigen atopy in this selected population. Allergy can contribute to a number of otologic symptoms, including eustachian tube dysfunction, vertigo, tinnitus, hearing loss, aural fullness, and nonspecific balance disturbance. Allergy also has been emphasized as an etiologic factor in a portion of patients diagnosed with Meniere's syndrome. A screening RAST, combined with clinical evaluation, appears to be an excellent tool for evaluating these patients for inhalant allergy as part of a comprehensive workup.

[Sudden deafness and increased toxoplasmosis IgM titer]. / Hörsturz und erhöhter IgM-Titer für Toxoplasmose.

BACKGROUND: Prenatal damage of the inner ear due to infection with toxoplasma gondii is documented. Nevertheless, there are only a few references about postnatal acquired toxoplasmosis as a cause of inner ear damage. PATIENTS: We report about a nine-year-old boy who suffered from unilateral hearing loss and tinnitus. RESULTS: Examinations did not show any other sign of a possible cause of hearing loss except for a very high toxoplasmosis titer of 1:102400. Besides our usual therapy regime for acute hearing loss, we treated the patient with pyrimethamine and sulphadiazine. Antibody titer decreased but the sensorineural hearing loss did not change substantially. Fortunately the patient lost the tinnitus. CONCLUSIONS: Acute Toxoplasmosis should be considered in the diagnostic process of sudden hearing loss, at least if there are appropriate clues in the medical history.

[The significance of genetic markers in otosclerotic hearing loss]. / Znachenie nekotorykh geneticheskikh markerov pri otoskleroticheskoi tugoukhosti.

Phenotypes HLA-A, HLA-B and HLA-C were determined in 85 patients with otosclerosis verified at surgery and in 113 clinically healthy subjects. The patients were divided into 2 groups: with family predisposition to otosclerosis (13 subjects) and without such (72 subjects). A tendency was established to more frequent occurrence of antigens A2, B12 versus less frequent of antigens B27, B40, Cw1 in patients compared to controls. It is concluded that at least one of the genes determining the resistance to otosclerosis exists in the HLA region, in binding groups B27, B40 and Cw1. It is suggested that genes predisposing to the disease (A2, B12) may be located at the same place.

[Progressive inner ear diseases--sequelae of a secondary autoimmune process? Significance of antibodies to endoplasmic reticulum]. / Progressive Innenohrerkrankungen--Folge eines sekundären autoimmunen Prozesses? Bedeutung von Antikörpern gegen endoplasmatisches Retikulum.

In sera from patients with different forms of inner ear diseases antibodies against endoplasmic reticulum (anti-ER) could be detected by ELISA in association with antisarcolemmal (ASA) and antiendothelial antibodies (AEA). 36% of 296 patients with sensorineural hearing loss (SNHL), 30% of 20 patients with tinnitus, 21% of 48 patients with sudden deafness and 20% of 49 patients with Menière's disease had ASA. 94% of these ASA positive patients were also positive for anti-ER. The overall frequency of anti-ER was 57% of patients with SNHL, 60% of patients with tinnitus, 46% of patients with sudden deafness and 22% of patients with Menière's disease. Analysing the clinical course in 5 anti-ER positive and 11 anti-ER negative patients with SNHL it was shown that all 5 patients either had a progressive course and/or a systemic manifestation in contrast to only 4 of the anti-ER negative patients. Anti-ER antibodies were also detected in 38-53% of patients with different chronic inflammatory disorders of unknown aetiology (polymyalgia rheumatica, vasculitis, sarcoidosis, ankylosing spondylitis etc.) while only 6% of patients with typical autoimmune disorders (collagen diseases, lupoid hepatitis, primary biliary cirrhosis) and 8% of blood donors had this antibody. Therefore it can be concluded that anti-ER antibodies have no apparent relevance for the diagnosis of SNHL. They may be, however, indicative of a secondary autoimmune process triggered by a persistent infectious agent.