Inner Ear Deafness Research Articles

A Novel Homozygous Mutation in the EC1/EC2 Interaction Domain of the Gap Junction Complex Connexon 26 Leads to Profound Hearing Impairment

To date, about 165 genetic loci or genes have been identified which are associated with nonsyndromal hearing impairment. In about half the cases, genetic defects in the GJB2 gene (connexin 26) are the most common cause of inner-ear deafness. The genes GJB2 and GJB6 are localized on chromosome 13q11-12 in tandem orientation. Connexins belong to the group of “gap junction” proteins, which form connexons, each consisting of six connexin molecules. These are responsible for the exchange of ions and smaller molecules between neighboring cells. Mutational analysis in genes GJB2 and GJB6 was brought by direct sequencing of the coding exons including the intron transitions. Here we show in the participating extended family a homozygous mutation c.506G>A, (TGC>TAC) p.Cys169Tyr, in the GJB2 gene, which could be proven for the first time and led to nonsyndromal severe hearing impairment in the afflicted patients. The mutation is located in the EC1/EC2 interaction complex of the gap junction connexon 26 complex and interrupts the K+ circulation and therefore the ion homeostasis in the inner ear. The homozygous mutation p.Cys169Tyr identified here provides a novel insight into the structure-function relationship of the gap junction complex connexin/connexon 26.

Hearing Preservation and Nanotechnology-based Targeted Drug Delivery Future in Cochlear Implantation?

Cochlear Implantation (CI) remains as one of the greatest medical achievements in modern medicine. New and innovative strategies continue to be developed to optimize and improve the functional results of CI surgery. Preservation of residual hearing through a-traumatic surgical techniques and electrode arrays may alter indications. Conditions with profound SNHL with preserved low tone hearing may have several causes and pathology may vary accordingly. In patients with progressive adult-onset SNHL neurons may be conserved even after long duration of deafness. IHCs and OHCs, supporting cells, ganglion cells and dendrites may be preserved in the apical region while in the lower turn despite atrophic organ of Corti and loss of lamina fibers ganglion cells can be present even after 28 years duration of deafness. These spiral ganglion cells may be excellent targets for electric stimulation using EAS technique that combines electric and acoustic stimulation in the same ear and utilizes both low frequency acoustic hearing and electric stimulation of preserved neurons. At the moment we are trying to elucidate the mechanism responsible for this preservation in humans and to use this knowledge for future therapy. Nano-technology may offer new possibilities for focused release of drugs and possibly genes to the inner ear. European project“NanoEar”is a concerted action to develop 3rd generation of nanoparticles (NP) for treatment of inner ear deafness. One goal is to target drugs and genes to specific inner ear cells through so-called multifunctional NP which are degradable, non-toxic, traceable and can be released in a controlled and biocompatible way. The small size of the NP may give new properties for technical advancement but risks must also be thoroughly evaluated. Uppsala is a Swedish partner to evaluate NP uptake in vitro in both human and animal spiral ganglion neurons. In my presentation I will show the system of culture spiral ganglion cells and demonstrate their locomotive behaviour and NP intracellular uptake using time lapse video recording and combined immunofluorescence and confocal microscopy.

Komplikationen im Verlauf eines Muckle-Wells-Syndroms

A 35-year-old woman had since early childhood suffered from recurrent urticaria-like rash, intermittent fever, arthralgia and pancochlear inner-ear deafness. At the age of 17 years she also developed a steroid-resistant nephrotic syndrome, found to be due to renal amyloidosis (type AA). The triad of renal amyloidosis, inner-ear deafness and recurrent urticaria is characteristic of Muckle-Wells syndrome, which has a hereditary basis. Rapidly progressive renal failure necessitated long-term haemodialysis and two renal transplantations. The accompanying immunosuppressive treatment with corticosteroids, azathioprin and, later, cyclophosphamide brought about a remission of the joint and skin abnormalities. After removal of the first donor kidney and termination of immunosuppressive treatment the syndrome recurred with subacute growth of an amyloid goitre as well as amyloidosis of the optic nerve. A few weeks before death a malignant non-Hodgkin lymphoma of the stomach was demonstrated. It was presumably a complication of long-term immunosuppression and not of the Muckle-Wells syndrome. The patient died of the complications of combination chemotherapy. Necropsy revealed generalized amyloidosis.

Autoantibodies to inner ear and endothelial antigens in Cogan's syndrome

Cogan's syndrome is a chronic inflammatory disease of unknown origin, characterised by sensorineural hearing loss, episcleritis, and vasculitis. An autoimmune origin has been suggested but not proven. Our aim was to establish whether or not an autoimmune process is the cause of the disease. We used pooled IgG immunoglobulins derived from eight patients with Cogan's syndrome to screen a random peptide library to identify disease relevant autoantigen peptides. Among the identified peptides, one was recognised by all the patients' sera. Antibodies against peptides were affinity purified from patients' sera and used to characterise the autoantigen, to stain human cochlea, and to transfer the features of Cogan's disease into animals. We identified an immunodominant peptide that shows similarity with autoantigens such as SSA/Ro and with the reovirus III major core protein lambda 1. The peptide sequence shows similarity also with the cell-density enhanced protein tyrosine phosphatase-1 (DEP-1/CD148), which is expressed on the sensory epithelia of the inner ear and on endothelial cells. IgG antibodies against the peptide, purified from the patients' sera, recognised autoantigens and DEP-1/CD148 protein, bound human cochlea, and inhibited proliferation of cells expressing DEP-1/CD148. The same antibodies bound connexin 26, gene mutations of which lead to congenital inner-ear deafness. Furthermore, these antibodies were able to induce the features of Cogan's disease in mice. Our results indicate that Cogan's syndrome is an autoimmune disease, characterised by the presence of autoantibodies able to induce tissue damage on binding of cell-surface molecules present on the sensory epithelia of the inner ear and on endothelial cells.

Familial syndrome of diabetes mellitus, primary optic nerve atrophy and inner-ear deafness

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

A new autosomal-recessive hereditary syndrome. Multiple peripheral pulmonary stenosis, brachytelephalangia, inner-ear deafness, ossification or calcification of cartilages

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Myopathia oculo-pharyngealis tarda hereditaria

A case of late-developing hereditary oculopharyngeal myopathy in a man of 58 is described. Increasing difficulty in eating and drinking developed gradually over about 10 years. In addition to weakness of the masticatory muscles and atrophy of the muscles of the face, the case presented a pronounced bilateral myogenic blepharoptosis. Examination of the siblings led to discovery of several further cases, indicative of an autosomal dominant inheritance. This condition has been frequently observed and described in Canada, but is hitherto almost unrecognized in Europe. Attention is drawn to the possible combination with slowly progressing inner-ear deafness.

Progressive Traumatic Inner-ear Deafness

Progressive Traumatic Inner-ear Deafness

Bone conduction-speech audiometry as a supplementary measuring method before operations for improvement of hearing

SUMMARYIn pure-tone audiometry we can get so-called “feeling curves” from totally deaf people. In hard-of-hearing patients with a questionable combined high degree of deafness, it is often impossible to discern whether bone conduction is true or felt. Measurements with masking do not lead to a clear diagnosis, either. In such uncertain cases, we write speech audiograms for air and bone conduction as well. Contrary to the yes/no statement in pure-tone audiometry, speech audiometry in air and bone conduction definitely gives more objective results. There is a pure inner-ear deafness when the two curves coincide. The exceeding bone conduction curve of a speech audiogram shows exactly the real part of the conductive hearing loss and enables us to get a better indication for operations in the middle ear.

Clinical studies of perceptive deafness due to middle ear lesions in children

Study was made of the perceptive deafness due to middle ear lesions in children.Therapeutic effect of cortisone (per os), X-ray radintion to the eustachian tube or adenotomy was examined respectively on the deafness with 79 ears in 41 children, and cortisone was found to be most effective.Following are the findings on property of the deafness obtained by comparison with the cases in adults.1. In adults there occured the unilateral as well as the bilateral lesions, but most of the children were of the bilateral.2. Sudden onset of hearing loss was commonly seen in adults, whereas gradual loss of hearing was frequent in children.3. Early treatment was rather effective on both adult and infant.4. Patients with inflammatory changes in the tympanic cavity, the eustachian tube and the nasopharynx gave quite succesful results of the treatment.5. The best results were obtained in the cases which showed a type of gradual loss toward the high tone and yet with a difference less than 10db between 500cps and 1000cps in the bone conduction audiogram. An increace of such difference reduced the effectiveness of therapy.From the above findings the conclusions are attained that the perceptive deafness due to middle ear lesions may be a type of pure perceptive deafness or of mixed deafness caused by the inflammatory changes in the nasopharnx, the eustachian tube and the tympanum, being devided into two types, acute (sudden deafness) and chronic (gradually progressive deafness), and that in the children with complication of such as oto-salpingitis and/or adenoiditis this type of deafness may easily induced and yet sometimes may develop to a pure inner-ear deafness.

TWO CASES INFANTILE PERCEPTIVE DEAFNESS RELIEVED BY THE TREATMENT OF THE NASOPHARYNX

Case 1. 6 years old girl. On the hearing test, her both perceptive organs of inner ears was impaired, and hearing loss was about 60db. After adenotomy, the patient's sujective symptoms, such as otalgia, tinnitus and deafness diappeared promptly. Her hearing acuity was within the normal limits on the eighth day after the operation. Case 2. 7 years old girl. Patient's right ear was totally deaf and the left ear showed percepti- ve deafness with 35db. hearing loss. X ray irradiation of Eustachian tube was done on the left side. After the treatment her hearing improved, and audiometrical test proved her left ear had the normal hearing. Reviewing the literature, there are some reports that after tonsillectomy or sinus operation for the patients with the innerear deafness, their hearing remarkably improved. These two cases are considered due to an allergic reaction in the labyrinth caused by focal infection.

Mastoid Asymmetry and Inner-Ear Deafness: An Unusual Case

Mastoid Asymmetry and Inner-Ear Deafness: An Unusual Case