Can miR-34a be suitable for monitoring sensorineural hearing loss in patients with mitochondrial disease? A case series.

Purpose: We aimed at evaluating the feasibility of using MicroRNA (miR)-34a and miR-29b to detect inner ear damage in patients with mitochondrial disease (MD) and sensorineural hearing loss (SNHL).Material and Methods: Three patients with MD and SNHL and seven healthy control subjects were included in this case series. MD patients underwent pure tone audiometry (PTA), distortion product otoacoustic emission (DPOAE) and auditory brain response tests to investigate the specific cochlear and retrocochlear functions; control patients underwent PTA. MiR-34a and miR-29b were extracted from blood in all subjects included in the study. The expression of miR-34a and miR-29b in MD patients and healthy controls were statistically compared, then the expression of these two miRs was compared with DPOAE values.Results: In MD patients, miR-34a was significantly up-regulated compared to healthy controls; miR-34a and DPOAEs were negatively correlated. Conversely, miR-29b was up-regulated only in the youngest patient who suffered from the mildest forms of MD and SNHL, and negatively correlated with DPOAEs.Conclusion: In MD patients, miR-34a and miR-29b might be a marker of inner ear damage and early damage, respectively. Additional studies on larger samples are necessary to confirm these preliminary results.

Superior semicircular canal dehiscence postoperative outcomes: A case series of 156 repairs.

Previous studies have looked at differences in predisposing factors, symptomology, treatment options, and outcomes in patients with SSCD experiencing audiologic and vestibular symptoms, however this study utilizes data from the largest series of SSCD patients by a single pair of neurosurgeon and head and neck surgeon to date. The objective was to determine what pre-operative factors, if any, contribute to post-operative outcomes in SSCD patients. A retrospective chart review collected patient demographics, preoperative symptoms, and postoperative symptoms. Nonparametric tests were run using IBM® SPSS® Statistics. Fisher's Exact Tests, Spearman's rho, and McNemar's test for paired comparison of binary measures were performed, with a significance level of P < 0.05. A total of 156 SSCD surgeries were performed within a cohort of 119 patients. The majority of patients were female (n = 75, 63.0%). The median age was 55 years (±12.7 years) and median follow-up length was 0.46 months (range: 0.03-59.5 months). Increased postoperative dizziness and hearing loss was significantly correlated with females (P = .048, P = .041). Additionally, males reported significantly improved postoperative hearing (P = .044) with confirmatory audiometry. Serum ionized calcium levels inversely correlated with age using spearman's coefficient (rs = -.260 P = .037). Postsurgical autophony was significantly associated with bilateral SSCD (P = .01). In conclusion, differences in outcomes between patients may have to do with bilateralism of SSCD or gender effects. Proposed theories concerning a "two hit" hypothesis and about calcium feedback regulation in SSCD may play a role in these findings. Understanding differences between symptomology will help facilitate discussions with future patients.

miR­10b­3p, miR­8112 and let­7j as potential biomarkers for autoimmune inner ear diseases.

Circulating microRNAs (miRNAs) have been suggested as non­invasive biomarkers for the diagnosis of several autoimmune diseases. However, to the best of our knowledge, no studies have yet examined the miRNA expression profiles in autoimmune inner ear disease (AIED). The present study aimed to use an miRNA sequencing assay to detect the miRNA expression profiles of serum samples from 3 control mice and 3 antigen­induced AIED model mice. Differentially expressed miRNAs (DE­miRNAs) were screened using a t­test. miRNA target prediction was performed using TargetScan Mouse. Then, the miRNA­target gene interaction network was constructed and visualized using Cytoscape software. The underlying functions of the target genes of the DE­miRNAs were predicted using the clusterProfiler package. As a result, 22 miRNAs were identified as DE­miRNAs between AIED and control mice, including 10 upregulated and 12 downregulated genes. Based on the TargetScan Mouse prediction, 1,958 genes were identified as the targets for the 22 DE­miRNAs. Functional analysis indicated that only the target genes of 8 miRNAs were respectively enriched for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways, among which miR­10b­3p, let­7j and miR­8112 were shared between the two pathway analyses. These 3 miRNAs may be involved in AIED by affecting inflammatory chemokine (miR­10b­3p­C­C motif chemokine 12), Wnt signaling (miR­8112­Wnt9b/Wnt 3a/Wnt2b) and Mucin type O­glycan biosynthesis pathways (let­7j­Galnt2/Galnt12). In conclusion, miR­10b­3p, miR­8112 and let­7j may be underlying biomarkers for diagnosing AIED.

The Balance of Tissue Inhibitor of Metalloproteinase-1 and Matrix Metalloproteinase-9 in the Autoimmune Inner Ear Disease Patients.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a protein implicated in the control of inflammation in a number of autoimmune diseases. We hypothesized that the balance of TIMP-1 and matrix metalloproteinase-9 (MMP-9) may influence the control or perpetuation of inflammation in corticosteroid-responsive (RES) and corticosteroid-resistant (NR) autoimmune inner ear disease (AIED) patients. In the present study, we observed that plasma from AIED patients exhibited greater levels of TIMP-1 values compared with normal healthy controls. TIMP-1 abrogates lipopolysaccharide-mediated interleukin (IL)-1ß release from peripheral blood mononuclear cells in a dose-dependent manner. RES AIED patients have higher basal TIMP-1 levels and produce more TIMP-1 in response to IL-1ß. Conversely, consistent with our previous studies, we found that NR patients have higher basal MMP-9 levels and produce more MMP-9 levels in response to IL-1ß.

Anti-endothelial serum antibodies in a patient with Susac's syndrome.

BACKGROUND: Susac's syndrome (SS) is a rare arteriopathy affecting the microvasculature of the brain, retina, and inner ear, resulting in encephalopathy, branch retinal artery occlusion and hearing loss. Anecdotal reports exist on SS being associated with a humoral immune response against endothelial cells. However, no original data has ever been published. OBJECTIVE: To analyze serum and CSF from a patient with SS for the presence of CNS auto-antibodies and, if present, to further characterize such antibodies immunologically. METHODS: Serum and CSF samples were examined by indirect immunofluorescence on adult mouse cerebrum, cerebellum, brain stem, and inner ear tissue sections, and IgG subclasses were determined. RESULTS: Anti-endothelial antibodies were found at a titre of 1:960 in serum but not CSF. Antibodies belonged to the complement activating IgG1 subclass. Glucocorticoid treatment resulted in a decrease of titres (1:480), though the antibodies remained clearly detectable. CONCLUSION: Our finding of anti-endothelial cell antibodies in a patient with SS is important in the light of previous pathological data suggesting that SS is associated with endothelial damage. Larger serological studies are now warranted to assess systematically the frequency and relevance of auto-antibodies in SS.

Selective vulnerability of the inner ear to decompression sickness in divers with right-to-left shunt: the role of tissue gas supersaturation.

Inner ear decompression sickness has been strongly associated with the presence of right-to-left shunts. The implied involvement of intravascular bubbles shunted from venous to arterial circulations is inconsistent with the frequent absence of cerebral symptoms in these cases. If arterial bubbles reach the labyrinthine artery, they must also be distributing widely in the brain. This discrepancy could be explained by slower inert gas washout from the inner ear after diving and the consequent tendency for arterial bubbles entering this supersaturated territory to grow because of inward diffusion of gas. Published models for inner ear and brain inert gas kinetics were used to predict tissue gas tensions after an air dive to 4 atm absolute for 25 min. The models predict half-times for nitrogen washout of 8.8 min and 1.2 min for the inner ear and brain, respectively. The inner ear remains supersaturated with nitrogen for longer after diving than the brain, and in the simulated dive, for a period that corresponds with the latency of typical cases. It is therefore plausible that prolonged inner ear inert gas supersaturation contributes to the selective vulnerability of the inner ear to short latency decompression sickness in divers with right-to-left shunt.

The inner ear in patients with nasal allergy.

BACKGROUND: The endolymphatic sac has been proposed as a target organ responsible for inner-ear symptom in allergic subjects. This is a report of inner-ear symptoms in patients with nasal allergy. METHOD: Retrospective review of record charts of patients with known nasal allergy presenting to the otorhinolaryngology out-patient department of the University College Hospital, Ibadan in 5 years. RESULT: Ear symptoms were found in 95/144 (66%) subjects with nasal allergy. This comprises of 41 males and 44 females (M: F = 1:1). Of these, itching of the external ear canal, hearing loss and tinnitus accounted for 63 (66%), 55 (58%) and 39 (41%), respectively, while vertigo was found in 12 (13%). Peripheral vestibular signs of imbalance were seen in 11/95. The audiological assessment of 73 subjects revealed normal pure-tone average in 43 (59%), and sensorineural hearing loss (SHL) in 17 (23.3%). The severity of SHL was mild in 6/17, moderate in 7 and moderate-to-severe in 4. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated in 10/15 (67%) and 6/15 (40%), while the skin sensitivity test showed reactions to dust in 32, cold in 25, cockroach in 7, perfume in 11, vegetable oil in 1 and insecticide in 2. The clinical diagnoses were idiopathic tinnitus in 25 (26.3%), Idiopathic SHL in 17 (18%), cochlear hydrop in 6 (6%) and autoimmune inner-ear disease in 6 (6%). CONCLUSION: This report suggests some peculiar predisposition to inner-ear pathology in patients with nasal allergy. However a longitudinal assessment of cochleovestibular features of nasal allergy subjects will help in its validation.

A direct HPLC method to estimate streptomycin and its putative ototoxic derivative, streptidine, in blood serum: application to streptomycin-treated humans.

Streptomycin is an aminoglycoside antibiotic with a well-known antituberculosis activity; it is commonly used in clinical practice because it is effective and cheap. However, streptomycin has severe ototoxic effects. The delayed and gradual onset may suggest that a metabolic derivative of the antibiotic could be a potential contributor to ototoxicity. As in a rat experimental model this compound was found to be streptidine, we investigated whether this ototoxic metabolite was also present in the blood of streptomycin-treated patients. To this end, we implemented and optimized a direct reverse-phase HPLC technique to identify and estimate streptomycin and streptidine in serum of streptomycin-treated patients. All criteria for validation of the method were implemented in standard curves in serum of healthy non-treated volunteers by addition of increasing concentration of both compounds and their determination in a trichloroacetic acid deproteinized extract. We found that recovery of streptomycin or streptidine was > or =91.5%. Linearity was r(2)> or =0.99. The intraday and interday precisions were < or =9.7 and < or =10.6%, respectively. The relative intraday and interday error ranged from -9.0 to 8.3% for both compounds in human serum. Studies in patients included five male individuals treated from 35 to 90 days with 1g/day of streptomycin, presenting inner ear malfunction from mild to severe, in whose serum streptidine was always present, and could be successfully separated from streptomycin. Therefore, the validated method used can be a valuable tool to measure and follow these compounds in serum of streptomycin-treated patients.

Protein profile of human perilymph: in search of markers for the diagnosis of perilymph fistula and other inner ear disease.

Recent developments in high-resolution two-dimensional polyacrylamide gel electrophoresis, combined with amino acid sequencing and computer-assisted image analysis, have allowed separation of approximately 100 proteins and identification and quantitation of some 30 proteins in human perilymph. The majority of proteins were found to be present in perilymph at levels in basic agreement with the total protein gradient between perilymph and plasma (1:35). However, several striking differences were observed: (1) beta 2-transferrin, known to be absent from normal plasma but present in cerebrospinal fluid, was detected in perilymph at a concentration roughly equal to that in cerebrospinal fluid; and (2) two high-density lipoprotein-associated apolipoproteins--apo D (formerly PLS:33) and apo J or NA1 and NA2 (formerly PSL:29/30), the latter showing identity with SP40/40, or cytolysis inhibitor--were found to be present at concentrations 1 to 2 orders of magnitude higher when examined in terms of total protein and to be comparable with or higher than plasma levels when examined in terms of absolute concentrations. The functional significance of the extremely high levels of the two apolipoproteins is not known at this time. An attempt was made to use beta 2-transferrin, as well as apo D and apo J (NA1/NA2), as markers for the diagnosis of perilymph fistula, one of the most controversial and challenging problems for the otologist today. It was determined that the technique is indeed applicable when relatively pure fistula samples are analyzed. Limitations and potential improvements of the technique are discussed. In addition, the potential usefulness of two-dimensional polyacrylamide gel electrophoresis in other pathologic conditions of the inner ear is discussed briefly.

[Protein fractions in workers with vestibular disorders]. / Sustoianie na beltuchnite fraktsii pri rabotnitsi s vestibularni narusheniia.

Study is performed on 133 patients with vestibular disturbances with no data for inflammatory diseases. Their age group is from 30 to 60, divided into three clinical syndromes: peripheral, central and combined. The otoneurological examination is carried out after the classic clinical scheme; and the blood test is taken in the morning before breakfast. It was established some tendencies between the rate of the pathological changes in the blood protein formula, the duration of the disease and the age. Considerable dynamic changes are registered in young patients, tendency for relative hypoalbuminemia, relative hypergammaglobulinemia etc. The changed coefficient albumin/globulins which in our patients is under the average norm is analyzed. The low values of this coefficient respond to the observed tendency for hypoalbuminemia in patients with vestibular disturbances.

[Otoneurological and biochemical research on the drivers of motor vehicles]. / Otonevrologicheni i biokhimichni izsledvaniia pri vodachi na motorni prevozni sredstva.

The aim of the study is to follow up the changes in auditory and vestibular systems, common interactions between the sensory systems and the changes in some biochemical indices after vestibular loading in drivers. Several groups of drivers of heavy freight trucks were studied, aged from 25-60 and a length of service from 5 to 30 years, according to a standard programme for otoneurological examination and application of modern otoneurological methods. The biochemical investigations were performed to 32 healthy and 19 sick drivers with vestibular disorders, prior to and post vestibular provocation. The following biochemical indices were studied: serotonin, histamine, cholinesterase activity, glucose, GOT, GPT, alkaline phosphatase, calcium, potassium, sodium, chlorides, inorganic phosphorus. The biochemical changes, associated with vestibular loading of organism were established not to be strongly manifested and coming out of the frames of the normal values, nevertheless, they are significant for a given subject and should not be neglected. The data are of importance in the vocational selection of driver-applicants, prophylaxis and treatment of those working under stress situations and extreme impacts.

Rheological effects of pharmacological treatment of inner ear disorders.

Improvement of the rheological quality of circulating blood is an important factor in pharmacological treatment of inner disorders. Diminution of blood viscosity by increased fluidity of red blood cells and hemodilution was studied in two patient groups, one treated by pentoxifylline per os (Trental 400, Höchst) and dextran infusions, the other one by dextran infusions only. The dextran effect is a short-term hemodilution, i.e. decreased viscosity is identical to hematocrit reduction. Long term, however, there is a significant increased viscosity in the dextran group. A significant constant effect on blood viscosity is warranted by pentoxifylline. Oral administration of this drug prevents the long-term blood thickening effect of dextran and leads to a permanent improvement of microcirculation.

Glucose, insulin and inner ear pathology.

One hundred consecutive patients with a clinical suspicion of metabolic inner ear disorder were submitted to a 5-hour glucose tolerance test with simultaneous titration of insulin. It was found that 82% of the patients presented abnormal glucose and/or insulin values. The analysis of the results revealed hypo- or hyperglycemia were present in only 41% of the cases, and that all patients had normal fast values for glucose. Hyperinsulinemia was the most frequent abnormality and was found to constitute the determining factor of the inner ear disorders. 26 of the patients presented Meniere's disease. The pathophysiological model for insulin-induced Meniere's disease is discussed. Follow-up data indicate that these patients respond well to a diet with reduced intake of small molecule carbohydrates.

[Evaluation of platelet function and coagulation in deafness and sudden vestibular disorders]. / Valutazione della funzionalità piastrinica e della coagulazione nella sordità e nelle turbe vestibolari improvvise.

Thirty-five patients affected by acute vestibular dysfunction (A.V.D.) and/or sudden deafness (S.D.) were studied. Twenty-seven of them presented, as major component of the clinical disorder, a vestibular dysfunction, eight a sudden deafness. The control group was matched for sex, age, smoking habit and family history of diabetes and myocardial infarction. In all the subjects the following tests were carried out: platelet aggregation (Born's method), PF3 (Spaet and Cintron), PF4 and BTg (RIA), aPTT, AT III, cholesterol and triglycerides. The results indicate in the patients group increase of P.A.: SAV = 27 vs 43% (p = 0.03) at 1.2 X 10(-6) M ADP, a larger availability of PF3 in PPP and PRP, increase of PF4: 7.2 vs 17.2 (p = 0.01) and BTg: 32.4 vs 49.1 (p = 0.009). The data indicate in A.V.D. and S.D. a platelet hyperactivity; if so, an antiplatelet therapy may be reasonable.

[Total cholesterol and high-density lipoprotein cholesterol in sensorineural deafness]. / Colesterolo totale e colesterolo associato alle lipoproteine ad alta densità (HDL) nell'ipoacusia neurosensoriale.

In order to verify an assumed hypothesis of a correlation between sensorial hearing loss and arteriosclerosis type injuries, these parameters were studied: total cholesterol and cholesterol associated to high density lipoproteins in order to evaluate the risk of developing coronary heart disease in patients with cochleopathy as compared to control patients. It proved impossible to point out any significant difference between results obtained in the two groups for any of the analytical parameters considered.

[Lipoproteins in cochleovestibular disorders (author's transl)]. / Lipoproteinmuster bei cochleovestibulären Störungen.

Forty-nine patients with neuro-otologic symptoms were examined with regard to their risk factors, especially their lipoproteins. No essential differences were found in the serum triglyceride and serum cholesterol levels. LDL-cholesterol and the quotient LDL-cholesterol/HDL-cholesterol were significantly higher in the group of patients. We consider this an indication for a relation between arteriopathy and cochleovestibular disorders.