Functional hearing loss and developmental imbalances.

OBJECTIVE: Functional hearing loss (FHL) is a disorder in which there are abnormal values on a hearing test, despite the absence of organic abnormalities in the peripheral and central auditory pathways. Here, we examined the developmental characteristics of FHL and the importance of intervention by analyzing the clinical characteristics of children with this disorder. METHODS: We retrospectively examined 16 patients assessed under a diagnosis of FHL. After interventions such as psychological counseling by our pediatrics and psychiatry departments, we compared the clinical profiles of patients in which hearing was "improved/normalized" and "unimproved". RESULTS: Fourteen patients visited a pediatrician and two chose not to do so. A discrepancy between the maximum and minimum values of the four index scores was observed in all patients in which WISC-IV (the fourth version of the Wechsler Intelligence Scale for Children) was performed (n = 12). The discrepancy between the verbal comprehension index (VCI) and perceptual reasoning index (PRI) was significantly greater in "unimproved" patients than in "improved/normalized" patients. Hearing improved, or was normalized, after intervention in six of 16 patients. CONCLUSIONS: Developmental imbalances were suspected in all 12 children who visited a pediatrician and completed the WISC-IV. Cooperation with pediatricians, psychiatrists, and other health professionals is desirable in supporting patients diagnosed with FHL.

Treatment of oral ranula in HIV-positive patient.

HIV-associated salivary gland disease refers to the pathology in head and neck lesions such as ranula, salivary gland swelling, xerostomia, and benign lymphoepithelial cysts in the parotid gland. Here, we present a unique case of the ranula patient with HIV infection treated with OK-423 sclerotherapy. Case report: The patient was a 42-year-old Japanese male with a few months history of oral floor swelling. Computed tomography (CT) showed a low-density area limited within the right floor of the mouth. Magnetic resonance imaging (MRI) revealed a distinct T2-high intensity area localized on the same location. The puncture fluid was bloody mucus, and the cytology was no malignancy. We diagnosed a simple ranula. He was, however, found to be HIV-antibody positive at the examination before treatment by chance. He was referred to the department of infectious diseases and definitively diagnosed HIV infection by western blot. We chose OK-432 sclerotherapy because of its minimally invasive and the risk of HIV infecting medical staff. Two times OK-432 injection made the lesion disappear. Conclusion: The case indicated that OK-432 sclerotherapy could be effective for ranula related to HIV.

Metastatic Renal Cell Carcinoma to the Left Sphenoid Sinus: A Case Report in Light of the Literature.

A 79-year-old Japanese woman presented with a rare case of metastatic renal cell carcinoma to the left sphenoid sinus with left nasal bleeding. She had previously had right radical nephrectomy for renal cell carcinoma at the age of 64 years and brain and spinal cord infarction at 74 years. Endoscopic examination revealed no mass in the nasal cavity. CT and MRI revealed a tumor in the left sphenoid sinus. The size of the tumor increased gradually from 12 to 15 years after the radical nephrectomy. Complete resection with endoscopic surgery was performed without preoperative embolization. The tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. These findings were identical to the pathological findings of the surgical specimen of the renal cell carcinoma from 15 years previous. A pathological diagnosis of metastatic renal cell carcinoma of clear cell type (grade 1) was made. PET-CT demonstrated no metastasis. The patient's condition was successfully managed with excision of the tumor, and she remains well with no evidence of recurrence and metastasis 36 months after treatment. Metastatic renal cell carcinoma to the sphenoid sinus is rare, but it might be considered in the differential diagnosis of masses in the paranasal sinus even long after initial treatment of renal cancer.

Malignancies in Patients with IgG4-Related Diseases in Head and Neck Regions.

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized disease, characterized by high serum IgG4 concentrations and IgG4-producing plasma cell expansion with fibrotic or sclerotic changes in affected organs. Recent work has focused on the relationship between IgG4-RD and malignancies, but there is no report of malignancies associated with IgG4-RD in head and neck regions. The aim of this study was to analyze the clinicopathological characteristics of malignancies in patients with IgG4-RD in head and neck regions. We retrospectively analyzed 26 patients with IgG4-RD (12 men and 14 women aged 60.6 ± 11.6 years). The mean follow-up period was 26.6 months (from 12 to 96 months). These patients were divided into single-lesion group (n = 12) with IgG4-RD only in head and neck regions and multiple-lesion group (n = 14) with IgG4-RD in other regions. There was no significant difference in serum IgG4 concentrations between the single-lesion group (459.4 ± 336.4 mg/dL) and the multiple-lesion group (908.0 ± 739.2 mg/dL) (P = 0.07), whereas the IgG4/IgG ratio was significantly lower in the single-lesion group (22.8 ± 11.0%; n = 11) compared with the multiple-lesion group (31.7 ± 15.0%; n = 11, P = 0.02). Among the 26 patients, two patients (7.7%), both in the multiple-lesion group, developed life-threatening malignancies (salivary duct carcinoma in the submandibular gland and lymphoma in the orbital tissue). All physicians need to keep in mind the possible coexistence of malignancies in patients with IgG4-RD with high IgG4/IgG ratio and multiple lesions at the time of diagnosis.

Treatment of Auricular Hematomas by OK-432: How and Why It Works.

OBJECTIVES: The aim of this article was to investigate the effectiveness and underlying mechanisms of OK-432 therapy in patients with auricular hematomas. STUDY DESIGN AND SETTING: Case series with planned data collection. SUBJECTS AND METHODS: We tried this therapy in 47 patients with auricular hematoma between April 2008 and August 2018. We aspirated as much of the fluid content of each lesion as possible with a 21-gage needle. We injected OK-432 solution into the lesion with the same needle that we used for aspiration. We performed this treatment at an outpatient basis without hospitalization. RESULTS: Disappearance and marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the auricle did not occur in any patients. As adverse effects, local pain at the injection site and fever (37-38.5°C) were observed in some cases of the patients who had this therapy. The concentrations of various cytokines in each aspirate before and after OK-432 therapy were investigated. The production of tumor necrosis factor-α, interleukin-6, interleukin-8, interferon gamma, vascular endothelial growth factor, and periostin was significantly elevated in the aspirate fluid after OK-432 therapy. CONCLUSION: OK-432 therapy is simple, easy, safe, effective, and can be used as a substitute for surgery in the treatment of auricular hematoma.

Endoscopic Treatment of Sinonasal Glomangiopericytoma: A Case Report in Light of the Literature.

A 71-year-old Japanese male patient presented with a rare case of Glomangiopericytoma (GPC) of the left nasal with obstruction. Complete resection with endoscopic surgery was performed. Immunohistochemical staining for smooth muscle actin, ß catenin, cyclin D1, vimentin, and factor 13 were helpful in establishing a definitive diagnosis. Extranasal treatment has been traditionally performed for successful management. However, recent advances in endoscopic treatment have enabled complete endoscopic resection of GPC, minimizing morbidity and facilitating subsequent surveillance for recurrence. Endoscopic management should be considered in suitable cases.

The expression of 11 beta hydroxysteroid dehydrogenase in severe allergic rhinitis.

OBJECTIVE: To clarify the roles of 11 beta-HSD in resistance to glucocorticoid therapy for allergic rhinitis, a case series study was conducted. METHODS: The patient group consisted of 20 subjects with allergic rhinitis, aged from 21 to 46 years (mean age 26.5), who showed persistent GC resistance necessitating surgical removal of the inferior turbinate after 6 months' GC treatment. The patients with poor response to GC treatment for 6 months' were defined as GC resistance. The control group consisted of 10 subjects aged from 16 to 39 years (mean age 24.5) who underwent maxillofacial surgery, from whom nasal tissues were taken and who did not receive GC treatment. Nasal mucosal tissues from patients and cntorol subjects were examined immunohistochemically. The sections were washed with 0.01 M phosphate-buffered saline (PBS; pH 7.2) containing 0.15 M NaCl and 0.01% Triton X-100, and incubated for 2 h with rabbit polyclonal anti-11 beta HSD1 and 11 beta-HSD2 antibody (Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA), each diluted 1:200 in PBS containing 0.1% bovine serum albumin. Immunostained sections were assessed under an Olympus microscope with an eyepiece reticule at 200 X magnification. Cell counts are expressed as means per high-power field (0.202 mm2). Control group means (arithmetic mean ± SD) were compared with patient group means by Mann-Whitney U-test at P = 0.05. RESULTS: Although 11 beta-HSD1 was expressed to a similar extent in patients and controls, 11 beta-HSD2 was expressed significantly more in patients with severe allergic rhinitis, resulting in a increased HSD-1/HSD-2 ratio. The significantly increased expression of 11 beta-HSD2 in the nasal epithelium and submucosal inflammatory cells of patients with severe nasal allergy were observed in the present study. CONCLUSION: Our findings suggest that 11 beta-HSD2 plays an important role in resistance to glucocorticoid therapy for allergic rhinitis, and its expression might be used as an additional parameter indicating steroid resistance in allergic rhinitis.

Ototoxic effect of daptomycin applied to the guinea pig middle ear.

CONCLUSION: Daptomycin applied topically at a concentration of 50 mg/ml caused mild but statistically significant hearing impairment. Outer hair cells were not damaged by daptomycin. Great care must be taken when there is a chance that daptomycin can reach the middle ear. OBJECTIVE: Ototopic antibiotic eardrops are frequently used to treat external and middle ear infections. Daptomycin is a new anti-methicillin-resistant Staphylococccus aureus (MRSA) drug with unknown ototoxicity. The current study examined the ototoxic effect of daptomycin in topical applications to guinea pig ears. METHODS: Twenty-three male Hartley guinea pigs (weight, 250-640 g) were divided into three groups receiving daptomycin (50 mg/ml), gentamicin (50 mg/ml, positive control), or saline solution (negative control). After insertion of a pressure-equalizing tube, pretreatment auditory brainstem responses (ABRs) were obtained. Topical solutions of 0.1 ml were applied through the tube into the middle ear twice a day for 7 days. Post-treatment ABRs were obtained 7 days after the last treatment. Hair cell loss was investigated with whole-mount cochlear surface preparations. RESULTS: The saline-treated (negative control) group showed no deterioration of ABR threshold. The daptomycin-treated group showed mild deterioration and the gentamicin-treated group showed severe deterioration in ABR threshold. Hair cells were preserved in the daptomycin- and saline-treated groups but severely damaged in the gentamicin group.

Change in endocochlear potential during experimental insertion of a simulated cochlear implant electrode in the guinea pig.

OBJECTIVE: Preservation of residual hearing during cochlear implantation is important. This study investigated changes in endocochlear potential (EP) during simulated cochlear implant (CI) electrode insertion. STUDY DESIGN: Laboratory animal study. SETTING: Academic hospital laboratory. SUBJECTS AND METHODS: Guinea pigs were divided into 4 groups: cochleostomy only (4 animals), suction after cochleostomy (5 animals), simulated CI electrode insertion parallel to the longitudinal axis of the scala tympani without suctioning (7 animals), and simulated CI electrode insertion toward the modiolus without suctioning (7 animals). The EP was measured from the second turn of the cochlea, and the values after 20 minutes were compared. RESULTS: The EP showed little change at 20 minutes after cochleostomy with a nearly normal value of 84.83 ± 2.12 mV. Suctioning of the perilymph from the cochleostomy site caused a slight acute reduction in EP by about 6 mV, and the value at 20 minutes after cochleostomy was 78.64 ± 4.42 mV. Insertion of the simulated CI electrode parallel to the longitudinal axis of the scala tympani caused a slight decrease in EP to 78.91 ± 5.06 mV. Insertion toward the modiolus caused a marked decrease in EP to 54.13 ± 4.42 mV at 20 minutes after the treatment, significantly lower compared with the other 3 groups. CONCLUSION: EP was well preserved during carefully performed surgical procedures of simulated CI electrode insertion, but it decreased significantly if the simulated CI electrode was inserted toward the modiolus. Careful attention is necessary to ensure the correct direction of CI electrode insertion to preserve residual hearing. Use of suction should be minimized if possible.

Sodium selectivity of semicircular canal duct epithelial cells.

BACKGROUND: Sodium absorption by semicircular canal duct (SCCD) epithelial cells is thought to contribute to the homeostasis of the volume of vestibular endolymph. It was previously shown that the epithelial cells could absorb Na+ under control of a glucocorticoid hormone (dexamethasone) and the absorptive transepithelial current was blocked by amiloride. The most commonly-observed target of amiloride is the epithelial sodium channel (ENaC), comprised of the three subunits α-, ß- and γ-ENaC. However, other cation channels have also been observed to be sensitive in a similar concentration range. The aim of this study was to determine whether SCCD epithelial cells absorb only Na+ or also K+ through an amiloride-sensitive pathway. Parasensory K+ absorption could contribute to regulation of the transduction current through hair cells, as found to occur via vestibular transitional cells [S. H. Kim and D. C. Marcus. Regulation of sodium transport in the inner ear. Hear.Res. doi:10.1016/j.heares.2011.05.003, 2011]. RESULTS: We determined the molecular and functional expression of candidate cation channels with gene array (GEO GSE6197), whole-cell patch clamp and transepithelial recordings in primary cultures of rat SCCD. α-, ß- and γ-ENaC were all previously reported as present. The selectivity of the amiloride-sensitive transepithelial and cell membrane currents was observed in Ussing chamber and whole-cell patch clamp recordings. The cell membrane currents were carried by Na+ but not K+, but the Na+ selectivity disappeared when the cells were cultured on impermeable supports. Transepithelial currents across SCCD were also carried exclusively by Na+. CONCLUSIONS: These results are consistent with the amiloride-sensitive absorptive flux of SCCD mediated by a highly Na+-selective channel, likely αßγ-ENaC. These epithelial cells therefore absorb only Na+ via the amiloride-sensitive pathway and do not provide a parasensory K+ efflux from the canals via this pathway. The results further provide caution to the culture of epithelial cells on impermeable surfaces.

Sodium selectivity of Reissner's membrane epithelial cells.

BACKGROUND: Sodium absorption by Reissner's membrane is thought to contribute to the homeostasis of the volume of cochlear endolymph. It was previously shown that the absorptive transepithelial current was blocked by amiloride and benzamil. The most commonly-observed target of these drugs is the epithelial sodium channel (ENaC), which is composed of the three subunits α-,ß- and γ-ENaC. However, other less-selective cation channels have also been observed to be sensitive to benzamil and amiloride. The aim of this study was to determine whether Reissner's membrane epithelial cells could support parasensory K+ absorption via amiloride- and benzamil-sensitive electrogenic pathways. RESULTS: We determined the molecular and functional expression of candidate cation channels with gene array (GEO GSE6196), RT-PCR, and whole-cell patch clamp. Transcript expression analysis of Reissner's membrane detected no amiloride-sensitive acid-sensing ion channels (ASIC1a, ASIC2a, ASIC2b) nor amiloride-sensitive cyclic-nucleotide gated channels (CNGA1, CNGA2, CNGA4, CNGB3). By contrast, α-,ß- and γ-ENaC were all previously reported as present in Reissner's membrane. The selectivity of the benzamil-sensitive cation currents was observed in whole-cell patch clamp recordings under Cl--free conditions where cations were the only permeant species. The currents were carried by Na+ but not K+, and the permeability of Li+ was greater than that of Na+ in Reissner's membrane. Complete replacement of bath Na+ with the inpermeable cation NMDG+ led to the same inward current as with benzamil in a Na+ bath. CONCLUSIONS: These results are consistent with the amiloride/benzamil-sensitive absorptive flux of Reissner's membrane mediated by a highly Na+-selective channel that has several key characteristics in common with αßγ-ENaC. The amiloride-sensitive pathway therefore absorbs only Na+ in this epithelium and does not provide a parasensory K+ efflux route from scala media.

Effect of vestibular labyrinth destruction on endocochlear potential and potassium concentration of the cochlea.

Partial labyrinthectomy can result in maintenance of hearing under certain circumstances, and the mechanism of the hearing impairment caused by labyrinthectomy is unclear. We hypothesized that disruption of the membranous labyrinth results in electrical leakage and electrolyte imbalance. This study investigated the change in cochlear function by measurement of endocochlear potential (EP) and potassium concentration ([K(+)]) caused by vestibular labyrinth destruction in the acute phase. Hartley guinea pigs underwent lateral semicircular canal (LSCC) transection with suctioning of the perilymph, ampullectomy, or destruction of the LSCC, superior SCC, and lateral part of the vestibule. The EP and [K(+)] were monitored using double-barreled ion-selective microelectrodes in the second turn of cochlea. The EP showed little to mild change after LSCC transectioning or ampullectomy, but declined variously and drastically after vestibulotomy. The EP did not recover but [K(+)] partially recovered after vestibulotomy. Disturbance of the mechanism of cochlear function caused by vestibular labyrinth destruction may involve reduction in the [K(+)] concentration in the endolymph.