Exercise-induced changes of gene expression in the cerebellum of aged mice.

PURPOSE: Exercise has been prescribed to the elderly based on its effect on increasing muscle strength and protein synthesis that prevent sense of balance and/or cognitive functions. However, a few molecular mechanism researches has been conducted on how the vestibular organs, cerebellum, and hippocampus, which are responsible for the deterioration and balance of spatial learning memory due to aging, are affected by exercise. METHODS: The 9-week old and 84-week old C57Bl/6 were assigned randomly to Young-Control (YC), Young-Exercise (YE), Old-Control (OC) and Old-Exercise (OE) groups for 4 -week treadmill running. A Rotarod test was used to evaluate motor coordination function. Moreover, a high-throughput whole transcript expression RNA array approach was applied to the cerebellum of aged mice to explain the novel molecular mechanism of beneficial effect of exercise. RESULTS: As results, the motor coordination function was significantly improved in exercise-aged mice. The RNA sequencing analysis showed that the expression of cerebellar genes was significantly changed by aging rather than exercise. Especially, Cers1 was up-regulated in sedentary aged mice and down-regulated in exercise aged mice. Fumonisin B1, inhibition of Cers1, mitigates neuronal cell death induced by doxorubicin. CONCLUSION: These results provide unraveling specific transcripts and understanding of the exercise-related cerebellum transcriptome in aged mice. Well-designed exercise program might prevent the motor coordination defect in aged model, which development of the exercise protocol for elderly population based on these markers.

Association between vestibular schwannomas and mobile phone use.

Vestibular schwannomas (VSs) grow in the region where the energy from mobile phone use is absorbed. We examined the associations of VSs with mobile phone use. This study included 119 patients who had undergone surgical tumor removal. We used two approaches in this investigation. First, a case-control study for the association of mobile phone use and incidence of VSs was conducted. Both cases and controls were investigated with questions based on INTERPHONE guidelines. Amount of mobile phone use according to duration, daily amount, and cumulative hours were compared between two groups. We also conducted a case-case study. The location and volume of the tumors were investigated by MRI. Associations between the estimated amount of mobile phone use and tumor volume and between the laterality of phone use and tumor location were analyzed. In a case-control study, the odds ratio (OR) of tumor incidence according to mobile phone use was 0.956. In the case-case study, tumor volume and estimated cumulative hours showed a strong correlation (r(2) = 0.144, p = 0.002), and regular mobile phone users showed tumors of a markedly larger volume than those of non-regular users (p < 0.001). When the analysis was limited to regular users who had serviceable hearing, laterality showed a strong correlation with tumor side (OR = 4.5). We found that tumors may coincide with the more frequently used ear of mobile phones and tumor volume that showed strong correlation with amount of mobile phone use, thus there is a possibility that mobile phone use may affect tumor growth.

Subthreshold continuous electrical stimulation facilitates functional recovery of facial nerve after crush injury in rabbit.

We sought to determine whether electrical stimulation (ES) with subthreshold, continuous, low-frequency impulses is a viable clinical method for improving functional recovery after facial nerve crush injury. In 10 rabbits, bilateral crush injuries were made on the facial nerve by compression for 30 s with mosquito forceps, causing complete facial paralysis. Subthreshold continuous direct current ES with 20-Hz square-wave pulses was applied to the proximal stump on one side for 4 weeks. Vibrissae movement returned significantly earlier on the ES side, with a less variable recovery time. Electrophysiologically, the stimulated side had a significantly shorter latency, longer duration, and faster conduction velocity. Light and transmission electron microscopy revealed that the electrical stimulation also markedly decreased Wallerian degeneration. The average numbers of fluorescent, double-labeled nerve cells were significantly different between the ES and non-ES sides. This study shows that subthreshold, continuous, low-frequency ES immediately after a crush injury of the facial nerve results in earlier recovery of facial function and shorter overall recovery time.

Clinical characteristics of acoustic trauma caused by gunshot noise in mass rifle drills without ear protection.

One of the major occupational hazards of working in military service is being subjected to intense impulse noise. We analyzed the clinical presentation of acoustic traumas, induced by mass rifle gunshot noise during military training, in unprotected patients. We evaluated 189 soldiers who had otologic symptoms after rifle shooting exercises without using any hearing protection. All soldiers had been training on the K2 rifle. We took medical histories; conducted physical examinations and hearing evaluations (pure-tone audiometry, speech audiometry, and impedence audiometry); and distributed the Newmann's Tinnitus Handicap Inventory (THI) survey. In addition, we evaluated a normal control group of 64 subjects of similar age who had never fired a rifle. In the patient group, the most common and irritating reported symptom was tinnitus (94.2%), and the average THI score in the patient group was 39.51 ± 14.87, which was significantly higher than the control group score (0.56 ± 3.94) (p < 0.001). Average outcomes of post-exposure air conduction thresholds were 21.33 ± 13.25 dB HL in the affected ears. These levels also were significantly higher than those of the control group (9.16 ± 4.07dB HL) (p < 0.001). Hearing loss was most prominent at high frequencies. An asymmetry of hearing loss related to head position during shooting was not observed. Acoustic trauma induced by gunshot noise can cause permanent tinnitus and hearing loss. Hearing protection (bilateral earplugs) and environmental reform are necessary.

Exercise reduces metabolic burden while altering the immune system in aged mice.

Although several evidence has suggested the impact of exercise on the prevention of aging phenotypes, few studies have been conducted on the mechanism by which exercise alters the immune-cell profile, thereby improving metabolism in senile obesity. In this study, we confirmed that 4-week treadmill exercise sufficiently improved metabolic function, including increased lean mass and decreased fat mass, in 88-week-old mice. The expression level of the senescence marker p16 in the white adipose tissue (WAT) was decreased after 4-weeks of exercise. Exercise induced changes in the profiles of immune-cell subsets, including natural killer (NK) cells, central memory CD8+ T cells, eosinophils, and neutrophils, in the stromal vascular fraction of WAT. In addition, it has been shown through transcriptome analysis of WAT that exercise can activate pathways involved in the interaction between WAT and immune cells, in particular NK cells, in aged mice. These results suggest that exercise has a profound effect on changes in immune-cell distribution and senescent-cell scavenging in WAT of aged mice, eventually affecting overall energy metabolism toward a more youthful state.

Clinical and molecular characterizations of novel POU3F4 mutations reveal that DFN3 is due to null function of POU3F4 protein.

X-linked deafness type 3 (DFN3), the most prevalent X-linked form of hereditary deafness, is caused by mutations in the POU3F4 locus, which encodes a member of the POU family of transcription factors. Despite numerous reports on clinical evaluations and genetic analyses describing novel POU3F4 mutations, little is known about how such mutations affect normal functions of the POU3F4 protein and cause inner ear malformations and deafness. Here we describe three novel mutations of the POU3F4 gene and their clinical characterizations in three Korean families carrying deafness segregating at the DFN3 locus. The three mutations cause a substitution (p.Arg329Pro) or a deletion (p.Ser310del) of highly conserved amino acid residues in the POU homeodomain or a truncation that eliminates both DNA-binding domains (p.Ala116fs). In an attempt to better understand the molecular mechanisms underlying their inner ear defects, we examined the behavior of the normal and mutant forms of the POU3F4 protein in C3H/10T1/2 mesodermal cells. Protein modeling as well as in vitro assays demonstrated that these mutations are detrimental to the tertiary structure of the POU3F4 protein and severely affect its ability to bind DNA. All three mutated POU3F4 proteins failed to transactivate expression of a reporter gene. In addition, all three failed to inhibit the transcriptional activity of wild-type proteins when both wild-type and mutant proteins were coexpressed. Since most of the mutations reported for DFN3 thus far are associated with regions that encode the DNA binding domains of POU3F4, our results strongly suggest that the deafness in DFN3 patients is largely due to the null function of POU3F4.

How long should the sudden hearing loss patients be followed after early steroid combination therapy?

To evaluate the beginning time and the completion time of hearing improvement in patients with sudden hearing loss who were treated with combination therapy including oral steroid. From September 2006 to December 2007, 102 idiopathic sudden hearing loss patients who showed any 'recovery' in hearing according to the Siegel's criteria after treatment were analyzed. Pure tone audiometries were performed on the pretreatment day and on the third, seventh, fourteenth post-treatment day, and on the first, second, third, sixth post-treatment month. The time of initial hearing improvement and the completion time of hearing improvement were analyzed. Of 102 patients who showed any improvement, cumulatively, 93.1% showed beginning of hearing improvement within 14 days after treatment. Complete recovery or an end of change was achieved in cumulatively 80.4% of the patients within 1 month after treatment and in 92.2% of the patients within 2 months after treatment. Prognosis can be predicted approximately 2 weeks after start of treatment because time of commencement shows plateau after 2 weeks in improved cases. Hearing should be followed-up for at least 2 months after treatment in patients who show incomplete or delayed hearing improvement.

Jugular foramen schwannoma: analysis on its origin and location.

OBJECTIVE: To examine the microsurgical anatomy of the jugular foramen and correlate anatomical findings to clinical manifestations of jugular foramen schwannomas concerning tumor origin and location. STUDY DESIGN: Anatomical analysis of jugular foramen was performed by dissection of 25 cadavers (50 sides). By retrospective review of 9 cases of jugular foramen schwannomas surgically treated, the origin and location of tumor were studied. SETTING: Tertiary referral center. MAIN OUTCOME MEASURES: The anatomical characteristics of jugular foramen, lower cranial nerves, and inferior petrosal sinus were correlated with the origin and growth pattern of jugular foramen schwannomas. RESULTS: The superior and inferior ganglions of the glossopharyngeal nerve and the superior ganglion of the vagus nerve were located within the jugular foramen. The superior ganglions of the glossopharyngeal and vagus nerves were located superiorly, whereas the inferior ganglion of the glossopharyngeal nerve was found inferiorly in relation to the inferior petrosal sinus orifice. In our series of 9 cases of jugular foramen schwannoma, the most common nerve of origin was the vagus nerve, followed by the glossopharyngeal nerve. CONCLUSION: The reason for the predilection of the jugular foramen schwannoma for the glossopharyngeal and vagus nerves may be associated with the presence of their ganglions within the jugular foramen. Also, the inferior petrosal sinus may act as a barrier to tumor growth, and the location of the ganglion of tumor origination within the jugular foramen in relation to the inferior petrosal sinus may be correlated to the predominant direction of tumor extension.

Surgical treatment and outcomes of temporal bone chondroblastoma.

Chondroblastoma is an uncommon primary benign bone tumor that usually arises in the epiphyses of the long bones. Temporal bone chondroblastoma is a rare primary bone tumor that affects the floor of the middle cranial fossa and temporomandibular joint (TMJ). The biological nature of temporal bone chondroblastoma is occasionally aggressive because of local invasion and is known to have a high recurrence after curettage. Therefore, complete resection is recommended. However, the literature provides little information regarding long-term surgical outcomes and complications after surgical resection. The authors have retrospectively analyzed four cases of temporal bone chondroblastoma that had been completely excised by a single surgeon with an eventual long-term follow-up. A single surgeon operated on four patients, two males and two females, with a mean age of 34 years, at the Department of Otorhinolaryngology, Severance Hospital. In all cases, the tumor involved the middle cranial fossa dura and the mandibular fossa with variable degree of infiltration. All patients have had no tumor recurrence to date (mean follow-up period of 5 years). Complete surgical resection of the temporal bone chondroblastoma is the gold standard for treatment. Precise preoperative image evaluation of tumor extension and proper management of the dura mater and temporomandibular joint (TMJ) are the major important features in complete surgical removal that minimize complications in temporal bone chondroblastoma treatment.

Clinical significance of quantitative analysis of facial nerve enhancement on MRI in Bell's palsy.

CONCLUSIONS: Quantitative analysis of the facial nerve on the lesion side as well as the normal side, which allowed for more accurate measurement of facial nerve enhancement in patients with facial palsy, showed statistically significant correlation with the initial severity of facial nerve inflammation, although little prognostic significance was shown. OBJECTIVES: This study investigated the clinical significance of quantitative measurement of facial nerve enhancement in patients with Bell's palsy by analyzing the enhancement pattern and correlating MRI findings with initial severity of facial palsy and clinical outcome. SUBJECTS AND METHODS: Facial nerve enhancement was measured quantitatively by using the region of interest on pre- and postcontrast T1-weighted images in 44 patients diagnosed with Bell's palsy. The signal intensity increase on the lesion side was first compared with that of the contralateral side and then correlated with the initial degree of facial palsy and prognosis. RESULTS: The lesion side showed significantly higher signal intensity increase compared with the normal side in all of the segments except for the mastoid segment. Signal intensity increase at the internal auditory canal and labyrinthine segments showed correlation with the initial degree of facial palsy but no significant difference was found between different prognostic groups.

Management of facial nerve schwannoma in patients with favorable facial function.

OBJECTIVE: We report six cases of facial nerve schwannomas in which surgical management allowed the preservation of facial nerve function. Specifically, this paper reports that a stripping surgery may provide favorable functional outcomes. STUDY DESIGN: A retrospective review of preoperative and postoperative data for six patients with facial nerve schwannoma that had normal facial nerve function or a House-Brackmann grade II facial palsy before the surgery. METHODS: Stripping surgery, which removed the schwannoma from the remaining nerve fascicle, was attempted on the six patients. Postoperative facial nerve function and imaging (magnetic resonance imaging) were evaluated. RESULTS: Stripping surgery with gross total tumor removal of the mass was performed in four cases. In the two remaining cases, the stripping surgery was not possible, and decompression alone was performed. Favorable preservation of facial function was achieved in all six cases. CONCLUSION: It was possible to preserve facial function after surgery to remove facial nerve schwannoma. We suggest that stripping surgery, focused on the preservation of continuity of the facial nerve, may be attempted for facial nerve schwannoma in which favorable facial function has been preserved.

Intracanalicular facial nerve schwannoma.

OBJECTIVE: To investigate the capability of preoperative evaluations in predicting the precise anatomic origin of intracanalicular tumors. STUDY DESIGN: We conducted a retrospective case review. SETTING: Tertiary referral center. PATIENTS: A total of 11 patients (8 men and 3 women, 26-70 years old) with intracanalicular tumors who were treated surgically were included. INTERVENTIONS: Pure-tone average, auditory brainstem response, caloric test, and temporal magnetic resonance imaging were done in all 11 patients. Electroneuronography has only been performed since 2003, and only 3 patients were evaluated. MAIN OUTCOME MEASURE: Preoperative symptoms, pure-tone average, auditory brainstem response, caloric test, electroneuronography, and magnetic resonance imaging were compared between patients with facial nerve schwannomas and patients with vestibular schwannomas. RESULTS: Postoperatively, facial nerve schwannomas were diagnosed pathologically in 2 (18%) of 11 patients. There were not any clues suggesting facial nerve schwannoma in preoperative evaluations. CONCLUSION: A facial nerve schwannoma may be misdiagnosed as a vestibular schwannoma, especially when the tumor is confined to the internal auditory canal. There are no useful preoperative evaluation tools in predicting the precise nerve origin of intracanalicular tumors. These emphasize the need to fully inform the patient preoperatively.

Correlation between MRI and operative findings in Bell's palsy and Ramsay Hunt syndrome.

PURPOSE: To investigate the correlation between gadolinium enhanced magnetic resonance image (MRI) results and surgical findings of facial nerves in Bell's palsy and Ramsay Hunt syndrome. MATERIALS AND METHODS: From 1995 to 2004, MRI was performed on 13 patients with Bell's palsy or Ramsay Hunt syndrome, who were offered with surgical decompression of the facial nerve through the middle cranial fossa approach. Gadolinium enhanced MRI was performed on all patients and the enhancement of the facial nerve was evaluated by radiology specialists. Operative findings including the degree of the facial nerve segment swelling were examined. Furthermore, the time interval from the onset of palsy to surgery was evaluated. RESULTS: Swelling of facial nerve segments was found in patients with enhanced facial nerves from MRI. The swelling of the facial nerve in the labyrinthine segment in particular was identified in all patients with enhanced labyrinthine segments in MRI. The intraoperative swelling of geniculate ganglion of facial nerve was found in 78% of patients with enhanced facial segment in MRI (p=0.01). The intraoperative swelling of tympanic segment was observed from fourth to ninth weeks after the onset of palsy. CONCLUSION: MRI enhancement of facial nerves in Bell's palsy and Ramsay Hunt syndrome is associated with the extent of intratemporal lesions of facial nerves, especially in the labyrinthine segment.

Wheel-shaped cartilage-perichondrium composite graft for the prevention of retraction pocket development.

CONCLUSION: Our technique can decrease the formation of retraction pockets and improve hearing function. The wheel-shaped cartilage-perichondrium composite graft (Wheel CPCG) can be considered a good material for a drum graft, and it is easy to insert a ventilation tube, in case of initial drum retraction. OBJECTIVE: The purpose of this study was to introduce the novel surgical technique of a Wheel CPCG with one-stage ossiculoplasty to prevent a retraction pocket and subsequent cholesteatoma after intact canal wall tympanomastoidectomy. PATIENTS AND METHODS: A total of 47 patients were reviewed; 43 cases were selected for audiologic testing. The results of operations were evaluated by comparing preoperative and postoperative hearing results and postoperative drum findings. RESULTS: A retraction pocket was observed in three cases (6.7%). Slight protrusion of partial ossicular replacement prosthesis (PORP) and lateral healing of drum was observed in one case each, and there were two cases of postoperative infection. The number of cases with an air-bone gap (ABG)<20 dB increased from 9 (23%) cases before operation, to 20 cases (51%) after operation. The ABG average statistically decreased from 30.0 dB to 24.0 dB, and the mean air conduction thresholds decreased from a preoperative level of 47.3 dB to a level of 35.7 dB.

Hearing results after ossiculoplasty using Polycel prosthesis.

CONCLUSIONS: Polycel is an effective material to use in ossiculoplasty. Good prognostic factors for hearing improvement after ossiculoplasty were healthy middle ear mucosa and the presence of stapes superstructure. OBJECTIVE: During the last decade, the surgical use of alloplasts has become increasingly widespread among otologists. This study aimed to evaluate the hearing results after ossiculoplasty using Polycel prosthesis. MATERIALS AND METHODS: We retrospectively reviewed 188 patients who underwent ossicular chain reconstruction using Polycel prosthesis and were followed up postoperatively for more than 12 months at Severance Eye-ENT Hospital from 1998 to 2002. Postoperative hearing results were assessed by measuring the postoperative air-bone gap (ABG) and closure of the ABG. Successful postoperative ABG criteria were defined as the following three measurements: ABG of

Response to galvanic vestibular stimulation in patients with unilateral vestibular loss.

OBJECTIVES: This study sought to characterize various responses to galvanic vestibular stimulation (GVS) by comparing GVS-induced eye movements in healthy subjects and patients with vestibular function loss. The study also aimed to estimate the clinical significance of GVS tests. Finally, an effort was made to localize the primary excitation site of stimulation in the vestibular system. MATERIALS AND METHODS: Three parameters of response to GVS, spontaneous nystagmus, galvanic stimulating nystagmus (GSN), and postgalvanic stimulating nystagmus (PGSN), were evaluated in 20 normal subjects and 14 patients with complete unilateral vestibular function loss resulting from labyrinthectomy or vestibular neurectomy using a three-dimensional video-electronystagmography technique. RESULTS: In normal subjects, GSN was detected in all subjects and was directed toward the negative electrode. PGSN was also detected but was directed toward the opposite electrode. When the negative electrode was attached to the intact side in unilateral vestibular loss subjects, GSN was always directed toward the negative electrode and PGSN was never observed. When the negative electrode was attached to the lesion side, however, GSN was detected in only one case, and PGSN was observed and directed to the intact side in 13 patients. CONCLUSIONS: The response to GVS in vestibular loss patients differed from that in normal subjects, which suggests that GVS could be useful for estimating the extent of vestibular function loss. The fact that the patterns of GVS response differed so significantly suggests that the primary site of excitation is not central but is instead the peripheral vestibular organ.

New method of identifying the internal auditory canal as seen from the middle cranial fossa approach.

OBJECTIVES: The middle cranial fossa approach allows one to remove acoustic tumors and preserve the facial nerve and hearing. However, there are no consistent landmarks on the surface of the temporal bone to identify the internal auditory canal. This study was designed to identify the internal auditory canal by use of external and internal references as seen during the middle cranial fossa approach. METHODS: We dissected 32 temporal bones using the middle cranial fossa approach and measured the distances from the posterior origin of the zygomatic arch to an imaginary coronal line between the foramen spinosum and the foramen ovale. We measured the angle between the lines drawn from the posterior origin of the zygomatic root to the foramen spinosum and from the foramen spinosum to the porus of the internal auditory canal. RESULTS: The distances were 14.7 mm and 22.9 mm, respectively, and the angle was roughly 90 degrees. CONCLUSIONS: In this study, we found external and internal landmarks that help to locate the internal auditory canal.

Compositional difference in middle ear effusion: mucous versus serous.

OBJECTIVES: Serous otitis media is usually responsive to medical treatment, whereas mucoid otitis media is not. The present study was undertaken to elucidate the compositional difference between serous and mucoid effusion and to investigate whether MUC5AC acts as a major mucin in the middle ear mucosa with mucoid otitis media. STUDY DESIGN: This study involved a chemical analysis of middle ear effusion and immunostaining of the middle ear mucosa. METHODS: Middle ear effusion samples were collected from 27 patients with mucoid otitis media and 18 patients with serous otitis media. The levels of mucin, lysozyme, secretory immunoglobulin A, and interleukin-8 were measured by dot blotting or enzyme-linked immunosorbent assay. Periodic acid-Schiff and immunohistochemical staining with monoclonal anti-MUC5AC antibody were performed on the serial sections of middle ear mucosa with mucoid otitis media. RESULTS: Mucoid effusions contained higher levels of mucin, lysozyme, secretory immunoglobulin A, and interleukin-8 than did serous effusions. Immunohistological study revealed that MUC5AC mucin was expressed in only a small portion of the goblet cells of middle ear mucosa with mucoid otitis media. CONCLUSIONS: The study suggests that both serous secretions and mucin might make the middle ear effusion more viscous and that mucins other than MUC5AC might have a major role in the viscosity of middle ear effusion. Further study is necessary to identify the major mucins in the middle ear effusion of otitis media with effusion.

Microsurgical anatomy of the perigeniculate ganglion area as seen from the middle cranial fossa approach.

The middle cranial fossa approach is useful for decompressing the perigeniculate ganglion area of the facial nerve in patients with serviceable hearing. The present study was designed to investigate the microsurgical anatomy of the perigeniculate ganglion area of the facial nerve from the point of view of the middle cranial fossa. We dissected 20 human temporal bones under a microscope using a middle fossa approach, and measured the angle between the lines drawn from the malleus head to the vertical crest and from the malleus head to the geniculate ganglion, and the distance from the malleus head to the geniculate ganglion. These were found to be 22.7 degrees +/- 2.2 degrees and 6.5 +/- 0.3 mm, respectively. Detailed knowledge about the microsurgical anatomy of the perigeniculate ganglion area of the facial nerve from the point of view of the middle cranial fossa is imperative for facial nerve decompression by a middle cranial fossa approach.