Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort.

The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice.

HDR syndrome, detected in the neonatal period by newborn hearing screening.

Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. Because HDR syndrome is caused by haploinsufficiency in GATA3, it exhibits variation in the onset and progression of hearing loss. In previous reports, the automated auditory brainstem response (AABR) was considered insufficient to detect sensorineural hearing loss caused by HDR syndrome. We report a case of HDR syndrome whose congenital hearing loss was detected by newborn hearing screening (NHS) using AABR. In this case, HDR syndrome was suspected due to hearing loss, hypocalcemia, and her family history. Genetic testing confirmed the diagnosis of HDR syndrome at 5 months of age. Because the phenotype of hearing loss due to HDR syndrome is variable and includes progressive hearing loss, these cases may not be detected by the HNS. However, most of the previous reports were published before the NHS became common and given the frequency of hearing loss complications in HDR syndrome. We consider that there is a reasonable number of HDR syndrome cases with abnormalities on the NHS. We believe that the NHS may also be useful for early detection of hearing loss due to HDR syndrome.

Long-term voice evaluation after arytenoid adduction surgery in patients with unilateral vocal fold paralysis.

PURPOSE: Laryngeal framework surgery, including medialization laryngoplasty and arytenoid adduction (AA), is expected to have a lasting or permanent effect in patients with unilateral vocal fold paralysis (UVFP); however, there are few reports about the long-term outcomes of AA. This study aimed to evaluate the long-term postoperative effects of AA surgery and examine its stability and reliability. METHODS: This study collected the voice handicap index (VHI) questionnaire from patients with UVFP who underwent AA more than 2 years previously. The VHI values preoperatively and 3 months postoperatively (early postoperative evaluation) were retrospectively calculated, and VHI values more than 2 years after surgery (late postoperative evaluation) were collected by mailing a sheet to the patients and asking to fill and return it. Possible influenced subscales such as age, sex, causes of UVFP, affected side, and surgeons were also analyzed. RESULTS: A total of 77 patients with UVFP who underwent AA had significantly lower early and late postoperative evaluations than preoperative evaluations. In 38 patients with no missing values, there were no significant differences between early and late postoperative evaluations, measured at a median of approximately 5 years. There were also no significant differences between early and late postoperative evaluations in any of the subscale groups. CONCLUSION: Patients with UVFP who underwent AA surgery achieved stable voice improvement in the long term after surgery.

Anatomy and function of the lymphatic vessels in the parietal pleura and their plasticity under inflammation in mice.

Inflammatory pleuritis often causes pleural effusions, which are drained through lymphatic vessels (lymphatics) in the parietal pleura. The distribution of button- and zipper-like endothelial junctions can identify the subtypes of lymphatics, the initial, pre-collecting, and collecting lymphatics. Vascular endothelial growth factor receptor (VEGFR)-3 and its ligands VEGF-C/D are crucial lymphangiogenic factors. Currently, in the pleura covering the chest walls, the anatomy of the lymphatics and connecting networks of blood vessels are incompletely understood. Moreover, their pathological and functional plasticity under inflammation and the effects of VEGFR inhibition are unclear. This study aimed to learn the above-unanswered questions and immunostained mouse chest walls as whole-mount specimens. Confocal microscopic images and their 3-dimensional reconstruction analyzed the vasculatures. Repeated intra-pleural cavity lipopolysaccharide challenge induced pleuritis, which was also treated with VEGFR inhibition. Levels of vascular-related factors were evaluated by quantitative real-time polymerase chain reaction. We observed the initial lymphatics in the intercostals, collecting lymphatics under the ribs, and pre-collecting lymphatics connecting both. Arteries branched into capillaries and gathered into veins from the cranial to the caudal side. Lymphatics and blood vessels were in different layers with an adjacent distribution of the lymphatic layer to the pleural cavity. Inflammatory pleuritis elevated expression levels of VEGF-C/D and angiopoietin-2, induced lymphangiogenesis and blood vessel remodeling, and disorganized the lymphatic structures and subtypes. The disorganized lymphatics showed large sheet-like structures with many branches and holes inside. Such lymphatics were abundant in zipper-like endothelial junctions with some button-like junctions. The blood vessels were tortuous and had various diameters and complex networks. Stratified layers of lymphatics and blood vessels were disorganized, with impaired drainage function. VEGFR inhibition partially maintained their structures and drainage function. These findings demonstrate anatomy and pathological changes of the vasculatures in the parietal pleura and their potential as a novel therapeutic target.

Anatomy and pathology of lymphatic vessels under physiological and inflammatory conditions in the mouse diaphragm.

The lymphatic vessels in the parietal pleura drain fluids. Impaired drainage function and excessive fluid entry in the pleural cavity accumulate effusion. The rat diaphragmatic lymphatics drain fluids from the pleura to the muscle layer. Lymphatic subtypes are characterized by the major distribution of discontinuous button-like endothelial junctions (buttons) in initial lymphatics and continuous zipper-like junctions (zippers) in the collecting lymphatics. Inflammation replaced buttons with zippers in tracheal lymphatics. In the mouse diaphragm, the structural relationship between the lymphatics and blood vessels, the presence of lymphatics in the muscle layer, and the distributions of initial and collecting lymphatics are unclear. Moreover, the endothelial junctional alterations and effects of vascular endothelial growth factor receptor (VEGFR) inhibition under pleural inflammation are unclear. We subjected the whole-mount mouse diaphragms to immunohistochemistry. The lymphatics and blood vessels were distributed in different layers of the pleural membrane. Major lymphatic subtypes were initial lymphatics in the pleura and collecting lymphatics in the muscle layer. Chronic pleural inflammation disorganized the stratified layers of the lymphatics and blood vessels and replaced buttons with zippers in the pleural lymphatics, which impaired drainage function. VEGFR inhibition under inflammation maintained the vascular structures and drainage function. In addition, VEGFR inhibition maintained the lymphatic endothelial junctions and reduced the blood vessel permeability under inflammation. These findings may provide new targets for managing pleural effusions caused by inflammation, such as pleuritis and empyema, which are common pneumonia comorbidities.

Malignant otitis externa presenting cerebral infarction from pseudoaneurysm: A case report and a review of the literature.

Chronic renal failure and diabetes mellitus could also be risk factors of pseudoaneurysm of the internal carotid artery (ICA) due to malignant otitis externa (MOE). Although pseudoaneurysm of the ICA is a rarely encountered disease, it should always be taken into consideration when treating patients of MOE.

Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.

Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

Middle ear adenoma with facial palsy: A case report and a review of the literature.

A 52-year-old man presented to our emergency department with an acute onset of right-sided facial nerve (FN) palsy of House-Brackmann grade V. Electroneurography (ENoG) was conducted with no response at the right FN, as compared with the left FN (0%). We performed a biopsy of the right middle ear mass and histological studies showed the tumor to be neuroendocrine tumors (NET) of the middle ear. We resected the tumor with canal wall down mastoidectomy and reconstructed the posterior meatal wall with soft tissue. Three months after surgery, the FN paralysis had improved with House-Brackmann grade II. We reviewed cases of NET with FN palsy, and nine patients, including our case, have been reported. Our case is the first report of ENoG for the description of FN palsy due to NET. Although the ENoG value was 0%, it was remarkably improved by surgery. The other cases of NET patients with FN palsy also recovered FN function after surgery. These results suggest that it is recommended to perform the total resection of the tumor to improve the FN function.

Underwater Endoscopic Ear Surgery for Closure of Cholesteatomatous Labyrinthine Fistula With Preservation of Auditory Function.

OBJECTIVE: To analyze the outcomes of the underwater endoscopic ear surgery (UWEES) technique for closure of cholesteatomatous labyrinthine fistula (LF) with preservation of auditory function. STUDY DESIGN: Retrospective case review study. SETTING: Tertiary referral center. PATIENTS: A total of 12 patients with cholesteatomatous LF. INTERVENTION: Surgical method of closure using UWEES for cholesteatomatous LF to minimize inner ear damage. Artificial cerebrospinal fluid (CSF) was used as the perfusate, except for earlier cases when saline was employed. MAIN OUTCOME MEASURES: Comparison of bone conductance hearing level (BCHL) before and after surgery. A change of BCHL less than 10 dB was defined as successful preservation of bone conductance hearing. RESULTS: All cases of LF were treated successfully by closure using the UWEES technique. Seven cases were type I, one was type IIa, and four were type III according to the Milewski and Dornhoffer classification of LF. The average LF size was 3.1 mm (1-7 mm). Eleven patients were evaluated and their bone conductance hearing was well preserved in all of them (11/11). One patient was too young for preoperative evaluation of BCHL, but hearing preservation was verified 2 years later at the age of 6 years. Remarkably, none of the patients complained of vertigo, except for only a slight manifestation on postoperative day 1. CONCLUSION: The UWEES technique was effective for closure of cholesteatomatous LF with preservation of auditory function.

A Novel Mutation in LMX1B (p.Pro219Ala) Causes Focal Segmental Glomerulosclerosis with Alport Syndrome-like Phenotype.

A 69-year-old woman presented with mild renal dysfunction, proteinuria, and sensorineural hearing loss. A renal biopsy showed focal segmental glomerulosclerosis with thinning of the glomerular basement membrane. There was a positive family history of end-stage kidney disease and hearing loss. Although Alport syndrome was suspected from these features, a genetic test using next-generation sequencer identified a novel missense mutation in LMX1B, c.655C>G: p. (Pro219Ala). In silico analyses predicted the pathogenicity of the mutation. Thus, the present case was diagnosed as LMX1B-associated nephropathy presenting with Alport syndrome-like phenotype, expanding the disease spectrum of LMX1B nephropathy.

Development and growth of auricular cartilage and muscles: A study using human fetuses.

OBJECTIVES: The auricle is a key target in pediatric plastic surgery and is considered to develop from a ring- or funnel-like arrangement of six hillocks in the embryo. However, there has been no report showing the morphologies of the auricular muscle and cartilage after midterm in humans. METHODS: We examined histological sections of 20 near-term human fetuses (29-40 weeks) and those from 7 midterm fetuses (15-16 weeks). RESULTS: At midterm, the auricular cartilage was a single wavy plate with the helicis major muscle (HMM). The superior and posterior auricular muscles (SAM, PAM) were inserted into the middle parts, and the anterior auricular muscle (AAM) was inserted into the lowest part of the cartilage plate, while the tragus and antitragus were not clearly identified. In near-term fetuses, the cartilage plate varied in size and shape between specimens. The scapha and antihelix were separated from the cartilage plate with major or minor involvement of the HMM from the initial mass along the helix. The SAM inserted to the crus helix or the developing scapha, while the insertion sites of the AAM and PAM into the helix were stable. The tragus-antitragus cartilages were well-developed and they sandwiched a deep notch of skin below the helix tail. The antitragicus muscle was more evident than the tragicus muscle. An unnamed muscle was evident along the external acoustic meatus. The other intrinsic muscles, including the transverse and oblique muscles, might develop from the HMM after birth. CONCLUSIONS: Development of the auricle was advanced after midterm. However, a single wavy plate-like cartilage was maintained until late-stage. Near term, the antihelix and scapha developed from the plate-like core of the auricle and the tragus and antitragus were added in the antero-inferior side of the cartilage plate. Establishment of muscle arrangements was markedly delayed compared to cartilage development. Altogether, the classical concept of an initial funnel-like arrangement of cartilage anlagen might have been biased by studies of adult morphology.

Characteristics of the Voice Handicap Index for Patients With Unilateral Vocal Fold Paralysis Who Underwent Arytenoid Adduction.

PURPOSE: This study was performed to evaluate the characteristics of the Voice Handicap Index (VHI), a self-assessment measure, for patients with unilateral vocal fold paralysis (UVFP) who underwent arytenoid adduction (AA), in comparison with postoperative vocal function examinations. METHODS: A retrospective chart review was conducted for patients who underwent AA at Tohoku University Hospital during the period between 2014 and 2017. VHI was compared before and after surgery; moreover, correlations were assessed between the VHI and other voice measurements, including perceptual assessment of voice, as well as aerodynamic and acoustic measures. Factors involved in the VHI score were explored by multivariate analysis. RESULTS: Forty-three UVFP patients (28 males, age 32-81 years; 15 females, age 34-80 years) were enrolled in the study; the average age of all patients was 61.5 years (32-81 years). Among the enrolled patients, 33 (76.7%) left and 10 (23.3%) right vocal folds were impaired. After surgery, nearly all of the patients exhibited significantly improved VHI score; each of the three subscales (functional, physical, and emotional) was also improved. The postoperative VHI correlated mildly with several values of the other voice measurements, with the exception of the mean flow rate. Multivariate analysis showed that the sole variable associated with postoperative VHI score was preoperative VHI. CONCLUSIONS: The postoperative VHI likely reflects improvement in the voices of the patients with UVFP. Although there were weak correlations with other voice measures, postoperative VHI is a relatively independent measurement parameter for patients with UVFP who underwent AA.

Complications of using Gore-Tex in medialization laryngoplasty: case series and literature review.

PURPOSE: This study was performed to evaluate the incidence and contributing factors of complications associated with medialization laryngoplasty using Gore-Tex in patients with unilateral vocal fold paralysis. METHODS: A retrospective chart review was conducted for all patients who underwent medialization laryngoplasty using Gore-Tex at Tohoku University Hospital between January 2014 and April 2018. A search of series and case reports in PubMed was performed to determine the incidence of complications following medialization laryngoplasty using Gore-Tex. RESULTS: Sixty-eight patient charts were reviewed. Two patients (2.9%) had complications (infection and extrusion into the airway) related to the Gore-Tex implant after surgery. In the 555 medialization laryngoplasty cases reported in both our current data and eight additional articles, there were 11 complications related to the Gore-Tex implant (2.0%). The most common event was extrusion into the lumen, which occurred in six cases (1.1%), followed by persistent inflammation with the granulation formation (0.5%). There were 12 cases of Gore-Tex extrusion (one male, six female, and five of unknown gender). The interval to onset ranged from 1 month to 10 years (median, 49 months). CONCLUSIONS: Our findings serve as a reminder that complications can occur with Gore-Tex implants following medialization laryngoplasty in patients with unilateral vocal fold paralysis, even in the long-term. We suggest that the use of excessively large implants in women and occurrence of postoperative hematoma followed by infection are factors that may cause complications. Nevertheless, Gore-Tex has been proven to be a relatively safe and reliable material for medialization laryngoplasty.

Incidence of Functional Nasal Voice in Patients With Patulous Eustachian Tube.

OBJECTIVE: Some patients with a patulous Eustachian tube (PET) complain of a nasal voice. This feature is often dismissed without further investigation. As such, there are only a few reports on this important symptom and scant studies have been conducted on a sufficiently large number of cases with PET. Therefore, this study was undertaken to investigate the characteristics of patients having a nasal voice and to examine whether this symptom can be an indication of the severity of PET. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. SUBJECTS AND METHODS: A retrospective survey of medical records in Sen-En Rifu Hospital identified 85 patients (40 men and 45 women) with PET between 2013 and 2016. Diagnosis of definite PET was based on the Proposal on Diagnostic Criteria of PET announced by the Otological Society of Japan (2017). The questionnaire inquired about the presence of a nasal voice and it was distributed to each patient at the first visit to the clinic. If a patient marked "yes" for the presence of nasal voice, he/she was later asked on the telephone to exclude nasal voice ascribable to causes other than PET, such as nasal diseases. Correlation between nasal voice and patient characteristics (age, sex, affected side, and PET symptoms such as autophony of own voice, aural fullness, and autophony of breathing sounds), subjective severity of PET evaluated by patulous Eustachian tube handicap inventory-10 (PHI-10), and that with the objective severity of PET evaluated by tubo-tympano-aerodynamic-graphy (TTAG) and sonotubometry were investigated. RESULTS: Seventy-six patients (36 men and 40 women) with definite PET were evaluated in this study. Thirteen patients (17.1%) (five men and eight women) reported a nasal voice coinciding with the occurrence of PET symptoms such as voice autophony, aural fullness, and breathing autophony. Age, sex, affected side, PET symptoms (autophony of their own voice, aural fullness, and autophony of their breathing sounds), and objective findings (TTAG and sonotubometry) were not significantly different between the two groups. The average total score of the PHI-10 in the "PET associated Nasal Voice Group" was 35.8 ±â€Š4.5, which was statistically higher than that of the "non PET associated Nasal Voice Group" 23.6 ±â€Š10.7 (p = 0.002). Out of 76 patients, 44 were treated surgically (Kobayashi Plug). In the "PET associated Nasal Voice Group," 85% (11 out of 13) were subjected to surgical treatment, whereas 52% (33 out of 63) underwent surgical treatment in the "non PET associated Nasal Voice Group." The rate of surgical treatment was significantly higher in "PET associated Nasal Voice Group" (p = 0.047). CONCLUSION: Nasal voice due to PET symptoms was observed in 17.1% of PET patients. It was generally found in patients with severe subjective symptoms. Nasal voice can be an indication of subjective severity. However, this study failed to show objective evidence of wider Eustachian tube in such cases. Patients with a nasal voice tended to seek vigorous treatment including surgery.

Enteric neurons of the esophagus: an immunohistochemical study using donated elderly cadavers.

PURPOSE: To describe and discuss the normal anatomy and function of enteric neurons in the esophagus of aged individuals. METHOD: We examined ganglion cells in esophagus specimens obtained from 15 elderly cadavers without any macroscopic pathology in the mediastinum and abdomen. Neuronal nitric oxide synthase and vasoactive intestinal polypeptide were used as parasympathetic nerve markers, and tyrosine hydroxylase as a sympathetic nerve marker. RESULTS: The thoracic and abdominal esophagus contained a well-developed myenteric nerve plexus (S100 protein-positive area) in the intermuscular layer: 0.02-0.03 mm2 per 1-mm length of the circular esophageal wall. The cervical esophagus usually contained no ganglion cells. The number of parasympathetic ganglion cells was maximal in the upper or middle thoracic esophagus (mean 18-23 cells per section), whereas sympathetic cells were considerably less numerous at any sites (mean 1-3 cells). CONCLUSION: In comparison with previous data from elderly cadavers, the esophagus carried much fewer ganglion cells than the intestine and colon; sympathetic cells were particular less numerous. Esophageal smooth muscle exhibits a unique mode of peristalsis characterized by a rebound contraction with a long latency after stimulation. This type of peristalsis appears to be regulated by inhibitory, nNOS-positive nerves with a sparse distribution, which seems to account for the long-span peristalsis unique to the esophagus. The extreme sparsity of ganglion cells in the cervical esophagus suggests that enteric neuron-integrated peristalsis, like that in the intestine and colon, is unlikely. Surgical treatment of the esophagus is likely to change or impair these unique features.

Is the ultimobranchial body a reality or myth: a study using serial sections of human embryos.

Reported morphologies of the ultimobranchial body had varied between researchers: a cluster of mitotic cells, a duct-like structure and a rosette-like cell mass. To clarify the true morphology, we studied tilted horizontal sections of 20 human embryos (crown-rump length 5-18 mm; 4-6 weeks). The sections displayed a ladder-like arrangement of the second to fourth endodermal pouches and, in 5 early embryos we found the fifth pouch attached to the fifth ectodermal groove near the fourth pharyngeal arch artery. The bilateral fifth pharyngeal pouches protruded anterolaterally to form a U-shaped lumen surrounding the arytenoid swelling. The third to fifth pouches were each characterized by a pedal-shaped inferior end. We identified several types of cell clusters as candidates for the ultimobranchial body, but morphologically most of them were, to various degrees, likely to correspond to the blind end of the lower pouch when cut tangentially. Because of the topographical relation to the common carotid artery, a cyst-like structure with a cell cluster seemed to be the most likely candidate of the ultimobranchial body (a common anlage of the thymus and parathyroid). However, we were not able to deny a possibility that a certain plane cutting the pouch end incidentally provided such a cyst-like structure in sections. At any stage, the ultimobranchial body might not appear as a definite structure that is discriminated from others with routine staining. A concept of the ultimobranchial body might be biased by comparative anatomy that shows the ultimobranchial gland in adult birds and reptiles.

NRF2 Is a Key Target for Prevention of Noise-Induced Hearing Loss by Reducing Oxidative Damage of Cochlea.

Noise-induced hearing loss (NIHL) is one of the most common sensorineural hearing deficits. Recent studies have demonstrated that the pathogenesis of NIHL is closely related to ischemia-reperfusion injury of cochlea, which is caused by blood flow decrease and free radical production due to excessive noise. This suggests that protecting the cochlea from oxidative stress is an effective therapeutic approach for NIHL. NRF2 is a transcriptional activator playing an essential role in the defense mechanism against oxidative stress. To clarify the contribution of NRF2 to cochlear protection, we examined Nrf2(-/-) mice for susceptibility to NIHL. Threshold shifts of the auditory brainstem response at 7 days post-exposure were significantly larger in Nrf2(-/-) mice than wild-type mice. Treatment with CDDO-Im, a potent NRF2-activating drug, before but not after the noise exposure preserved the integrity of hair cells and improved post-exposure hearing levels in wild-type mice, but not in Nrf2(-/-) mice. Therefore, NRF2 activation is effective for NIHL prevention. Consistently, a human NRF2 SNP was significantly associated with impaired sensorineural hearing levels in a cohort subjected to occupational noise exposure. Thus, high NRF2 activity is advantageous for cochlear protection from noise-induced injury, and NRF2 is a promising target for NIHL prevention.

Effect of intratympanic application of efinaconazole 10 % solution in the guinea pig.

Efinaconazole 10 % solution is a new triazole antifungal agent developed for the topical treatment of fungal infections of the nails. The current study examined the effect of intratympanic application of efinaconazole 10 % solution in the guinea pig ear. Sixteen male Hartley guinea pigs (weight 501-620 g) were divided into 3 groups to be treated with efinaconazole 10 % solution, gentamicin (50 mg/mL), or saline solution. Topical solutions of 0.2 mL were applied through a small hole made at the tympanic bulla once daily for 7 consecutive days. Post-intervention auditory brainstem responses were obtained 7 days after the last treatment. The extent of middle ear damage and hair cell loss was investigated. The efinaconazole- and gentamicin-treated groups showed severe deterioration in auditory brainstem response threshold. Middle ear examination revealed extensive changes in the efinaconazole-treated group and medium changes in the gentamicin-treated group. Hair cells were preserved in the efinaconazole- and saline-treated groups, but severe damage was seen in the gentamicin group. In conclusion, efinaconazole 10 % solution applied intratympanically to the guinea pig middle ear caused significant middle ear inflammation and hearing impairment.

Cricoarytenoid Articulation in Elderly Japanese With Special Reference to Morphology of the Synovial Tissue.

OBJECTIVE: To clarify composite fibers and cells in the synovial tissues of the cricoarytenoid joint (CA joint). METHODS: Routine histology and immunohistrochemistry using sagittal or nearly sagittal sections obtained from 18 elderly cadaveric specimens. RESULTS: The CA joint capsule was thin and contained few elastic fibers. A limited supportive ligament, namely, a thickened fascia of the posterior cricoarytenoid muscles, was sometimes evident on the lateral aspect of the CA joint. However, even in the weaker medial aspect of the joint, no marked destruction of the synovial tissues was found. The CA joint always contained synovial folds--a short medial fold and long lateral folds--but these contained no or few macrophages, lymphocytes, and blood capillaries. In 2 exceptional specimens showing inflammatory cell infiltration in the submucosal tissue of the larynx, the macrophage-rich area extended toward the capsule and medial synovial fold. CONCLUSIONS: The lateral aspect of the CA joint was likely to be supported mechanically by the muscle-associated tissues. Strong support of the arytenoid by muscles might reduce the degree of CA joint injury with age. However, some patients with hoarseness due to mucosal inflammation of the larynx might have accompanying synovitis and subsequent cartilage injury in the CA joint.