Vocal fold scarring is the foremost cause of voice disorders after vocal fold injury secondary to trauma, surgical treatment, and inflammation postinfection; however, present treatment approaches are limited. Induced pluripotent stem (iPS) cells are generated from fibroblasts through the introduction of 4 transcription factors - Oct3/4, Sox2, c-Myc, and Klf4; and because they are obtained from patient-derived somatic cells, they can prevent transplant rejection. Therefore, iPS cells are capable of unlimited symmetrical self-renewal, thus providing a limitless cell source for tissue-engineering applications. Vocal fold regeneration with stem cells is reviewed in this paper. We also show the feasibility of differentiating human iPS (hiPS) into stratified squamous epithelial cells for vocal fold regeneration.
Cochlear implantation improves hearing and speech ability in patients with profound or severe sensorineural hearing loss. However, its effects are limited when there is a primary auditory neuron response deficiency because the effects of cochlear implantation are dependent on the function of the cochlear nerve. Recently, cochlear implantation indications have been expanded, and even patients with residual hearing in the low-frequency range have received cochlear implantation. In this case, the preservation or regeneration of hair cells is necessary. To overcome the limitations of cochlear implantation and to achieve more effective outcome in cases of the expanded indication, it is necessary to preserve or regenerate spiral ganglion cells, i.e. primary auditory neurons, and hair cells, both of which never regenerate naturally in mammals. Previous experiments using animals showed that these were accomplished using growth factors or stem cells, which are the important tools of regenerative medicine. Even in clinical trials on human beings to treat idiopathic sudden sensorineural hearing loss, one of the growth factors, insulin-like growth factor 1 (IGF-1), was shown to be more effective than steroid therapy, indicating that this growth factor is useful for cochlear implantation. It is necessary to apply these results to cochlear implantation in the future.
Here we review the current situation of research and clinical practice relating to congenital hearing loss and introduce our approaches to these issues. Approximately 70% of patients with congenital hearing loss are caused by genetic mutations, and diagnosis of the genetic causes may lead to prediction of clinical features which would be useful for clinical diagnosis and therapy. This is especially valuable for infants in whom auditory tests cannot easily provide accurate information. In Japan, genetic tests for congenital hearing loss are covered by national health insurance. Because genetic information contains important personal information on the individual, it needs to be used cautiously. Genetic diagnosis and therapy should be appropriately included within the flow of clinical practice for hearing loss. Since the genetic causes of hearing loss are quite diverse, appropriate tests are necessary. As a new technology for genetic testing, a next-generation sequencer has been developed and its high performance has been reported. Many issues concerning genetic diagnosis and therapy remain to be resolved, and efforts to solve such problems are being made. In order to establish fundamental therapies for hereditary hearing loss, several approaches have been underway. As an example, we are currently conducting research on drug development using iPS cells from patients with hearing loss attributable to Pendred syndrome.
A rhythm reproduction task was performed using factors of rhythm patterns, addition of stress accent, and participants' music appreciation time in everyday life. Thirty-one deaf and twenty-four hearing participants attended the experiment. Three kinds of rhythm pattern were composed by varying the ratios of the inter-stimulus interval (ISI) of the constructing tone stimuli; 1: 2, 1: 3, and 1: 2: 3. Performance of rhythm reproduction by the participants was best with the 1: 2 ISI ratio rhythm, followed by the 1: 3 and 1: 2: 3 patterns in both groups. The deaf participants were divided into two groups based on whether or not they have music appreciation time in everyday life, and rhythm reproduction performance was higher in the group with such appreciation. Further, the addition of a stress accent in rhythm patterns promoted reproduction in both groups, especially in the group without music appreciation time. The results of this research revealed that patterns of difficulty in rhythm reproduction are similar in groups with and without hearing impairment, and music appreciation time and the addition of a stress accent promote rhythm reproduction.
The present study examined monthly training by a speech therapist augmented by 1 year of home training using synthetic voice for an adult who stutters. The home training was conducted 3-4 times per week, for 30-40 minutes each session. The contents of the training and the speech rates employed were carefully determined. The speech rate was first set at 4.6 morae per second (MPS), next at 5.0 MPS, and finally at 5.4 MPS. Psychological status relating to the stuttering symptoms was also evaluated during the same period. As a result of the training, the stuttering symptoms and psychological status were improved, suggesting that home training can play an important role as a complement to training by a speech therapist.
A 14-year-old boy presented recalcitrant mutational dysphonia with excessive tension of the muscles of his speech organs. The patient did not respond to any facilitating technique of voice therapy such as coughing, humming or hard glottal attack in producing low-pitched voice. Five sessions of voice therapy, including use of the "Kayser-Gutzmann" method in which the larynx is manually pulled downward before phonation, and tongue relaxation were necessary in order to obtain a normal low-pitched voice. After twelve sessions (four months) of voice therapy, stabilization of the low-pitched voice was accomplished. The fundamental frequency of the voice was lowered from 350 Hz before to 120 Hz after the treatment. At 2-years' follow-up, the normal low-pitched voice was successfully maintained but the patient used a falsetto voice at home. Most cases of mutational dysphonia respond well to voice therapy alone, and can easily achieve a complete and permanent low-pitched voice within several sessions of voice therapy. In some patients with recalcitrant mutational dysphonia, however, relatively long-term (4 to 6 months) and extensive voice therapy and long-term (1 to 2 years) follow-up are necessary.
Objective: To characterize voice changes over a period of 143 days in a female-to-male transsexual subject receiving hormone therapy. Patients and Methods: The subject was a 24-year-old female-to-male transsexual. Vocal assessment consisted of examination of the mean fundamental frequency (MF0), vocal range, the subject's impression concerning her own voice, and self-evaluation using the VHI scale. Results: MF0 started to decline after 48 days of therapy, and by 143 days it had descended from 187 Hz to 108 Hz. Vocal range widened from 138-1046 Hz to 97-1174 Hz after 48 days, and then narrowed to 82-392 Hz. Regarding subjective impression, at 48 days the subject complained of her voice breaking during conversation, and at 143 days difficulty of producing a falsetto voice while singing and feeling tense during conversations. VHI score improved for the emotional subscale, but deteriorated for the physical subscale. Conclusion: In the present subject, hormone therapy had the effects of decreasing the MF0 and temporarily widening the vocal range. However, the subject complained about voice symptoms as noted above. In this subject these symptoms seemed to be functional dysphonia derived from organic changes in laryngeal muscles. In order to prevent such symptoms, reconsideration of hormone quantity and the injection term may be necessary while observing voice changes.
In Japan, the average life expectancy is now 83 years —the longest of any country, according to 2013 World Health Statistics— and this super-aging society is getting older every year. Pneumonia is now the third most common cause of death in Japan, and dysphagia in the elderly has become a critical social issue. Dysphagia which is progressive triggers weight loss, immunological hyperfunction, and loss of the will to live, and the dysphagia itself inevitably continues to worsen further. In this report, I identify local and systemic changes relating to deglutition function in the aged. In the pharyngeal phase of swallowing especially, in the elderly swallowing reflex is delayed, deglutition momentum changes, and the upper esophageal sphincter resists opening. In terms of prophylaxis, stimulation of oropharyngeal sensory function, activation of the cortex to modulate swallowing, and exercise of the laryngeal levator muscles may be useful in the treatment of age-related swallowing disorders.
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