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Investigates the effect of interferon-gamma on human Clara cell secretory protein production in airway epithelial cells. Physiological benefits of Clara cells; Mechanisms of the epithelium; Antiviral properties of interferon.

To determine the presence and prevalence of regional contraction abnormalities in patients with angina pectoris, radionuclide ventriculography gated to an electrocardiogram was carried out in 22 control subjects (group 1) and in 22 patients with angina pectoris (group 2) with isolated stenosis of the left anterior descending coronary artery. No patients had had previous myocardial infarctions. A computer program subdivided the left ventricle into four regions at a geometric centre, and time-activity curves (30-40 ms/frame) of the global, septal, apical, and lateral regions were computed. There was no significant difference in the ejection fraction in the global or in any of the regions between the two groups. End systole in each region occurred close to global end systole in both groups. In the global region the percentage stroke volume ejected during the first third of systole was not significantly less in group 2 than in group 1. Regional analysis of the segments perfused by the stenosed vessel showed that the percentage stroke volume ejected during the first third of systole in group 2 was significantly less in the septal region and in the apical region compared with that in group 1. In contrast, in the normally perfused lateral region, there was no significant difference in the percentage stroke volume at the first third of systole between the two groups. This indicates that early contraction abnormalities are present in the region perfused by the stenosed vessel in patients with angina pectoris without previous myocardial infarction. Thus analysing the regional change in left ventricular volume during ejection in patients with coronary artery disease can show localised areas of contraction abnormalities during early systole that are not apparent when ventricular contraction is assessed as a whole. [ABSTRACT FROM PUBLISHER]

Objective: A well-known and frequently reported complication after cochlear implantation is the appearance of postoperative vertigo symptoms. Perilymphatic fistula (PLF) is a known cause for hearing loss and vertigo. Cochlin-tomoprotein (CTP) is a cochlear specific protein acting as a marker for PLF. Aim of the present study was to observe, if the postoperatively new occurence of vertigo is caused by a perilymphatic fistula evidenced by CTP marker . Methods: In a prospective analysis 12 cochlear implant patients with the postoperatively new occurence of vertigo underwent a transtympanally revison/resealing surgery. In all patients middle ear fluid was captured and analysed for CTP. Results: In 5 out of 12 patients a positive CTP result was found indicating a PLF. Positive PLF finding did not correlate with the intraoperative visual assumption of a leak. The procedure solves in most of the cases the vertigo problem. Conclusion: Our present finding demonstrates that objectively an insufficent sealing causing perilymphatic fistula occurs frequently in cases of newly postoperative vertigo after cochlea implantation. [ABSTRACT FROM AUTHOR]

Several surgical techniques have been documented for approaching and repairing superior semicircular canal dehiscence syndrome (SCDS). These techniques encompass the trans-middle cranial fossa, transmastoid, endoscopic approaches, and round window reinforcement (RWR). RWR entails the placement of connective tissue with or without cartilage and around the round window niche, restricting the round window's movement to minimize the 3rd window effect and restore the bony labyrinth closer to its normal state. We employed the multilayer RWR technique, resulting in significant postoperative improvement and long-lasting effects for 3.7 years in 2 cases. Here, we present the clinical findings, surgical procedures, and the effectiveness of multilayer RWR. This technique can be the initial choice for surgical treatments of SCDS due to its high effectiveness, longer-lasting effect, and minimal risk of surgical complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sawada, Matsuda, Tanzawa, Sakamoto, Kudo, Nakashima and Ikezono.)

Objectives: An idiopathic perilymphatic fistula (PLF) can be difficult to diagnose because patients present with sudden sensorineural hearing loss (SSHL) and/or vestibular symptoms without any preceding events. In such cases, we currently test for cochlin-tomoprotein (CTP) to confirm the diagnosis of idiopathic PLF because CTP is only detected in the perilymph. In this study, we report the clinical course of five patients definitively diagnosed with idiopathic PLF who underwent PLF repair surgery using transcanal endoscopic ear surgery (TEES)., Patients and Methods: Five patients were initially treated with intratympanic dexamethasone for SSHL, at which time a CTP test was also performed (preoperative CTP test). Due to refractory hearing loss and/or fluctuating disequilibrium, PLF repair surgery using TEES was performed to seal the oval and round windows using connective tissue and fibrin glue. These patients were diagnosed with definite idiopathic PLF based on pre- or intra-operative CTP test results (negative, < 0.4 ng/mL; intermediate, 0.4-< 0.8 ng/mL; and positive, > 0.8 ng/mL). We evaluated pre- and intra-operative CTP values, intraoperative surgical findings via a magnified endoscopic view, and pre- and post-operative changes in averaged hearing level and vestibular symptoms., Results: Pre- and intra-operative CTP values were positive and intermediate in three patients, positive and negative in one patient, and negative and positive in one patient. None of the patients had intraoperative findings consistent with a fistula between the inner and middle ears or leakage of perilymph. Only two patients showed a slight postoperative recovery in hearing. Four patients complained of disequilibrium preoperatively, of whom two had resolution of disequilibrium postoperatively., Conclusion: A positive CTP test confirms PLF in patients without obvious intraoperative findings. The CTP test is considered more sensitive than endoscopic fistula confirmation. We consider that CTP test results are important indicators to decide the surgical indication for idiopathic PLF repair surgery. In our experience with the five cases, two of them showed improvements in both hearing and vestibular symptoms., Competing Interests: Saitama Medical University, where HaM and TeI are affiliated, holds the patents for the hCTP ELISA test. This fact did not influence the results of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kubota, Ito, Furukawa, Matsui, Goto, Shinkawa, Matsuda, Ikezono and Kakehata.)

Objective: Vertigo is a quite frequent complication after cochlear implantation. Perilymphatic fistula (PLF) is assumed to be one cause of this problem. Cochlin tomoprotein (CTP) is a newly introduced marker for PLF. The present aim was to evaluate the rate of positive CTP testing in cases of newly occurring vertigo after cochlear implantation., Materials and Methods: Twelve patients with vertigo after cochlear implantation and a revisional electrode-sealing procedure underwent intraoperative rinsing of their middle ear. The sample was evaluated for CTP with monoclonal antibody testing. Sixteen controls from six CI patients were taken., Results: 4 out of 12 (33%) cases showed positive CTP testing, indicating that a PLF could be evaluated. In all of the positive CTP cases, surgery decreased the vertigo symptoms. A relation between the subjective visual assessment of a fistula and a positive CTP value was not observed. Controls confirmed the value of the testing., Discussion: CTP detection objectively shows that PLF can occur in patients with vertigo after CI.

Perilymph Fistula (PLF), abnormal communication between the fluid-filled space of the inner ear and the air-filled space of the middle ear, is a significant cause of vestibular and auditory symptoms. This is a retrospective study of 22 cases treated with PLF repair surgery, selected based on our surgical indication. We analyzed the characteristics of these 22 cases and evaluated the efficacy of PLF repair surgery in treating vestibular and auditory symptoms. Cases with antecedent events had significantly shorter intervals before surgery. The postoperative recovery from vestibular symptoms following PLF repair surgery was strikingly rapid, with 82% of cases demonstrating marked improvement within a week, even in chronic cases. Despite the notable absence of a control group in the study, the marked improvements in vestibular symptoms and substantial reductions in Dizziness Handicap Inventory (DHI) scores suggest that the observed benefits are attributable to the surgical intervention. Further, timely surgery showed improvements in hearing, with some benefits also seen in late-stage surgeries. Using the perilymph-specific protein Cochlin-tomoprotein (CTP) as a diagnostic biomarker, we could prove that PLF could be responsible for disequilibrium and related auditory disturbances in these patients. A new hypothesis is proposed that the chronic disequilibrium experienced by many PLF patients is due to enhanced mobility of the utricle and not to endolymphatic hydrops. Further research is needed to fully elucidate PLF's symptoms and treatment efficacy using the surgical indication we developed., Competing Interests: Saitama Medical University, where HM and TI are affiliated, holds the patents for the hCTP ELISA test. This fact did not influence the results of the study. The remaining author has no commercial or financial relationships that could be perceived as potential conflicts of interest., (Copyright © 2023 Matsuda, Hornibrook and Ikezono.)

Background: Empty nose syndrome (ENS) is caused by nasal turbinate surgery. The standard treatment for ENS is an inferior meatus augmentation procedure (IMAP) in which autologous tissue such as auricular cartilage, rib cartilage, or artificial material is transplanted into the nasal cavity. However, some challenges like a very small auricular cartilage are associated with these autologous tissue types. Moreover, since using rib cartilage is a highly invasive technique, the scar on the chest from where the harvesting is done is easily visible, and the artificial material is susceptible to infection. We used autologous dermal fat (ADF) in IMAPs in our study for the following reasons: the quantity of ADF could be increased or reduced as needed, ADF is considered a safer option than rib cartilage because it is harvested from superficial tissue, it is superior in terms of cosmetic appearance to harvested rib cartilage, and it has a lower risk of infection than any artificial material. Objective: The purpose of our study was to investigate the efficacy and safety of IMAPs using ADF. Methods: We included nine patients with ENS who underwent an IMAP using ADF. The patients' backgrounds and responses to the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) were recorded. Changes in each item of the ENS6Q before and after surgery (up to 3 months) were analyzed. Results: The postoperative ENS6Q total score and parameters were significantly better than their preoperative counterparts. Nasal dryness improved slightly less than other symptoms. There were no complications. Conclusions: The IMAP using ADF was effective in improving ENS symptoms; however, some physiological functions were difficult to improve, and dryness persisted. Autologous dermal fat is larger than auricular cartilage, less invasive than rib cartilage, and has a lower risk of infection than artificial material., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2021. The Author(s).)

Background: Non-contrast FLAIR revealed increased signal within the inner ear in patients with vestibular schwannoma, which is generally assumed to occur in the perilymph; however, the majority of previous studies did not differentiate between the endolymph and perilymph. Therefore, endolymph signal changes have not yet been investigated in detail. The purpose of the present study was three-fold: (1) to assess perilymph signal changes in patients with vestibular schwannoma on heavily T2-weighted (T2W) 3D FLAIR, also termed positive perilymphatic images (PPI), (2) to evaluate signal and morphological changes in the endolymph on PPI, and (3) to establish whether vertigo correlates with the signal intensity ratios (SIR) of the vestibular perilymph or vestibular endolymphatic hydrops., Methods: Forty-two patients with unilateral vestibular schwannoma were retrospectively recruited. We semi-quantitatively and qualitatively evaluated the perilymph signal intensity on the affected and unaffected sides. We also quantitatively examined the signal intensity of the vestibular perilymph and assessed the relationship between vertigo and the SIR of the vestibular perilymph on the affected side. We semi-quantitatively or qualitatively evaluated the endolymph, and investigated whether vestibular hydrops correlated with vertigo., Results: The perilymph on the affected side showed abnormal signal more frequently (signal intensity grade: overall mean 1.45 vs. 0.02; comparison of signal intensity: overall mean 36 vs. 0 cases) and in more parts (the entire inner ear vs. the basal turn of the cochlea and vestibule) than that on the unaffected side. No significant difference was observed in the SIR of the vestibular perilymph with and without vertigo (5.54 vs. 5.51, p = 0.18). The endolymph of the vestibule and semicircular canals showed the following characteristic features: no visualization (n = 4), signal change (n = 1), or vestibular hydrops (n = 10). A correlation was not observed between vestibular hydrops and vertigo (p = 1.000)., Conclusions: PPI may provide useful information on signal and morphological changes in the endolymph of patients with vestibular schwannoma. Further research is warranted to clarify the relationship between vertigo and the MR features of the inner ear., (© 2021. The Author(s).)

Human ACTG1 mutations are associated with high-frequency hearing loss, and patients with mutations in this gene are good candidates for electric acoustic stimulation. To better understand the genetic etiology of hearing loss cases, massively parallel DNA sequencing was performed on 7,048 unrelated Japanese hearing loss probands. Among 1,336 autosomal dominant hearing loss patients, we identified 15 probands (1.1%) with 13 potentially pathogenic ACTG1 variants. Six variants were novel and seven were previously reported. We collected and analyzed the detailed clinical features of these patients. The average progression rate of hearing deterioration in pure-tone average for four frequencies was 1.7 dB/year from 0 to 50 years age, and all individuals over 60 years of age had severe hearing loss. To better understand the underlying disease-causing mechanism, intracellular localization of wild-type and mutant gamma-actins were examined using the NIH/3T3 fibroblast cell line. ACTG1 mutants p.I34M p.M82I, p.K118M and p.I165V formed small aggregates while p.R37H, p.G48R, p.E241K and p.H275Y mutant gamma-actins were distributed in a similar manner to the WT. From these results, we believe that some part of the pathogenesis of ACTG1 mutations may be driven by the inability of defective gamma-actin to be polymerized into F-actin.

MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year; when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells with wildtype myosin 6 and espin1 co-expressed created long microvilli, while co-expression with mutant constructs resulted in severely shortened microvilli. In conclusion, the present data clearly showed that MYO6 is one of the genes to keep in mind with regard to ADSNHL, and the molecular characteristics of the identified gene variants suggest that a possible pathology seems to result from malformed stereocilia of the cochlear hair cells.

TECTA is well known as a causative gene for autosomal dominant mid-frequency hearing loss observed in various populations. In this study, we performed next-generation sequencing analysis of a large Japanese hearing loss cohort, including eight hundred and twelve (812) subjects from unrelated autosomal dominant hearing loss families, to estimate the prevalence and phenotype-genotype correlations in patients with TECTA mutations. The prevalence of TECTA mutations in Japanese autosomal dominant sensorineural hearing loss families was found to be 3.2%. With regard to the type of hearing loss, the patients with mutations in the nidogen-like domain or ZA domain of TECTA showed varied audiograms. However, most of the patients with mutations in the ZP domain showed mid-frequency hearing loss. The rate of hearing deterioration in TECTA -associated hearing loss patients and in the normal hearing Japanese control population were the same and regression lines for each group were parallel. We carried out haplotype analysis for four families which had one recurring missense variant, c.5597C>T (p.Thr1866Met). Our results revealed four different haplotypes, suggesting that this mutation occurred independently in each family. In conclusion, TECTA variants represent the second largest cause of autosomal dominant sensorineural hearing loss in Japan. The hearing loss progression observed in the patients with TECTA mutations might reflect presbycusis. The c.5597C>T mutation occurred in a mutational hot spot and is observed in many ethnic populations.

The OTOF gene (Locus: DFNB9), encoding otoferlin, is reported to be one of the major causes of non-syndromic recessive sensorineural hearing loss, and is also reported to be the most common cause of non-syndromic recessive auditory neuropathy spectrum disorder (ANSD). In the present study, we performed OTOF mutation analysis using massively parallel DNA sequencing (MPS). The purpose of this study was to reveal the frequency and precise genetic and clinical background of OTOF-related hearing loss in a large hearing loss population. A total of 2,265 Japanese sensorineural hearing loss (SNHL) patients compatible with autosomal recessive inheritance (including sporadic cases) from 53 otorhinolaryngology departments nationwide participated in this study. The mutation analysis of 68 genes, including the OTOF gene, reported to cause non-syndromic hearing loss was performed using MPS. Thirty-nine out of the 2,265 patients (1.72%) carried homozygous or compound heterozygous mutations in the OTOF gene. It is assumed that the frequency of hearing loss associated with OTOF mutations is about 1.72% of autosomal recessive or sporadic SNHL cases. Hearing level information was available for 32 of 39 patients with biallelic OTOF mutations; 24 of them (75.0%) showed profound hearing loss, 7 (21.9%) showed severe hearing loss and 1 (3.1%) showed mild hearing loss. The hearing level of patients with biallelic OTOF mutations in this study was mostly severe to profound, which is consistent with the results of past reports. Eleven of the 39 patients with biallelic OTOF mutations had been diagnosed with ANSD. The genetic diagnosis of OTOF mutations has significant benefits in terms of clinical decision-making. Patients with OTOF mutations would be good candidates for cochlear implantation; therefore, the detection of OTOF mutations is quite beneficial for patients, especially for those with ANSD., Competing Interests: The authors have declared that no competing interests exist.

Perilymphatic fistula is defined as an abnormal communication between the perilymph-filled space and the middle ear, or cranial spaces. The manifestations include a broad spectrum of neuro-otological symptoms such as hearing loss, vertigo/dizziness, disequilibrium, aural fullness, tinnitus, and cognitive dysfunction. By sealing the fistula, perilymphatic fistula is a surgically correctable disease. Also, appropriate recognition and treatment of perilymphatic fistula can improve a patient's condition and hence the quality of life. However, the difficulty in making a definitive diagnosis due to the lack of an appropriate biomarker to detect perilymph leakage has caused a long-standing debate regarding its management. We have reported a clinical test for the diagnosis of perilymphatic fistula by detecting a perilymph specific protein, Cochlin-tomoprotein, as a diagnostic marker using a western blot. The aim of this study is to establish an ELISA-based human Cochlin-tomoprotein detection test and to evaluate its diagnostic accuracy in clinical subjects. The results of ELISA showed good dilution reproducibility. The mean concentration was 49.7±9.4 of 10 perilymph samples. The ROC curve in differentiating the perilymph leakage condition from the normal middle ear was significant (P < 0.001) with an area under the curve (AUC) of 0.918 (95% CI 0.824-0.100). We defined the diagnostic criteria as follows: CTP<0.4 negative; 0.4≦CTP<0.8 intermediate; 0.8≦CTP(ng/ml) positive in the clinical usage of the hCTP ELISA, and sensitivity and specificity were 86.4% and 100%, respectively. We further tested the expression specificity of the Cochlin-tomoprotein by testing blood and CSF samples. The concentration was below the detection limit (0.2 ng/ml) in 38 of the 40 blood, and 14 of the 19 CSF samples. We report the accuracy of this test for the diagnosis of perilymphatic fistula. Using ELISA, we can improve the throughput of the test. Furthermore, it is useful for a large-scale study to characterize the clinical picture and delineate the management of this medical condition.

Background: Dizziness or vertigo is associated with both vestibular-balance and psychological factors. A common assessment tool is the Vertigo Symptom Scale (VSS) -short form, which has two subscales: vestibular-balance and autonomic-anxiety. Despite frequent use, the factor structure of the VSS-short form has yet to be confirmed. Here, we clarified the factor structure of the VSS-short form, and assessed the validity and reliability of the Japanese version of this tool., Methods: We conducted a cross-sectional, multicenter, psychometric evaluation of patients with non-central dizziness or vertigo persisting for longer than 1 month. Participants completed the VSS-short form, the Dizziness Handicap Inventory, and the Hospital Anxiety and Depression Scale. They also completed the VSS-short form a second time 1-3 days later. The questionnaire was translated into Japanese and cross-culturally adapted. We conducted a confirmatory factor analysis followed by an exploratory factor analysis. Convergent and discriminant validity, internal consistency, and test-retest reliability were evaluated., Results: The total sample and retest sample consisted of 159 and 79 participants, respectively. Model-fitting for a two-subscale structure in a confirmatory factor analysis was poor. An exploratory factor analysis produced a three-factor structure: long-duration vestibular-balance symptoms, short-duration vestibular-balance symptoms, and autonomic-anxiety symptoms. Regarding convergent and discriminant validity, all hypotheses were clearly supported. We obtained high Cronbach's α coefficients for the total score and subscales, ranging from 0.758 to 0.866. Total score and subscale interclass correlation coefficients for test-retest reliability were acceptable, ranging from 0.867 to 0.897., Conclusions: The VSS-short form has a three-factor structure that was cross-culturally well-matched with previous data from the VSS-long version. Thus, it was suggested that vestibular-balance symptoms can be analyzed separately according to symptom duration, which may reflect pathophysiological factors. The VSS-short form can be used to evaluate vestibular-balance symptoms and autonomic-anxiety symptoms, as well as the duration of vestibular-balance symptoms. Further research using the VSS-short form should be required in other languages and populations.

Usher syndrome is an autosomal recessive disorder manifesting hearing loss, retinitis pigmentosa and vestibular dysfunction, and having three clinical subtypes. Usher syndrome type 1 is the most severe subtype due to its profound hearing loss, lack of vestibular responses, and retinitis pigmentosa that appears in prepuberty. Six of the corresponding genes have been identified, making early diagnosis through DNA testing possible, with many immediate and several long-term advantages for patients and their families. However, the conventional genetic techniques, such as direct sequence analysis, are both time-consuming and expensive. Targeted exon sequencing of selected genes using the massively parallel DNA sequencing technology will potentially enable us to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using this technique combined with direct sequence analysis, we screened 17 unrelated Usher syndrome type 1 patients and detected probable pathogenic variants in the 16 of them (94.1%) who carried at least one mutation. Seven patients had the MYO7A mutation (41.2%), which is the most common type in Japanese. Most of the mutations were detected by only the massively parallel DNA sequencing. We report here four patients, who had probable pathogenic mutations in two different Usher syndrome type 1 genes, and one case of MYO7A/PCDH15 digenic inheritance. This is the first report of Usher syndrome mutation analysis using massively parallel DNA sequencing and the frequency of Usher syndrome type 1 genes in Japanese. Mutation screening using this technique has the power to quickly identify mutations of many causative genes while maintaining cost-benefit performance. In addition, the simultaneous mutation analysis of large numbers of genes is useful for detecting mutations in different genes that are possibly disease modifiers or of digenic inheritance.

Usher syndrome is an autosomal-recessive disorder that causes bilateral sensorineural hearing loss, retinitis pigmentosa (RP), and occasionally vestibular dysfunction. Usher syndrome types 1, 2, and 3 can be distinguished by differences in audiovestibular features. The objectives of this retrospective study were to evaluate 26 patients with Usher syndrome clinically. The 26 patients (male: 12 cases, female: 14 cases) with Usher syndrome, with a clinical diagnosis based on symptoms of bilateral sensorineural hearing loss and RP, had been registered from 13 hospitals as a multicenter study. We assessed the clinical history and performed audiovestibular and ophthalmologic examinations, and genetic testing. Eleven of the patients were classified as having Usher type 1 (38.5%), 6 with Usher type 2 (23.1%), and 9 with Usher type 3 (38.5%). However, many patients with atypical Usher type 1 (70%) and type 2 (83.3%) were found compared with Usher type 3 (10%). The conductive rate of vestibular examinations including the caloric test (50%) was low. There were many variations in the clinical symptoms in Usher syndrome patients, therefore the classification of Usher types 1, 2, and 3 has been complicated. We have proposed a flowchart for the diagnosis of Usher types 1, 2, and 3.

Dislocation of the arytenoid cartilage occurs following medical instrumentation involving the laryngeal cavity or laryngeal injury from outside the larynx. We reported a case of spontaneously posterior dislocation of the arytenoid cartilage. A 53 year-old man suffering from suddenly recurring aphonia and its improvement many over 3 months without laryngeal injury or inducement eventually ceased to improve. Laryngoscopic findings showed that the left vocal fold was tensely prolonged and the vocal process of the arytenoid cartilage on the left side was dislocated posterolaterally. X-ray videofluorography of the larynx on repetitive phonation of /he/ showed abnormally high and diagonal displacement of the vocal fold and the upper structure of the arytenoid cartilage on the left side. Palpating the cricoarytenoid joint on the left side showed abnormal swelling with tenderness. Electomyography of the intrinsic laryngeal muscle on the left side showed normal action potential. From these findings, we diagnosed his voice disorder as spontaneously posterior dislocation of the arytenoid cartilage. We manually reduced it by pulling up a balloon inserted from the piriform sinus of the affected side to the esophagus.

Objectives: To compare the usefulness of a CCD camera with infrared illumination (IR-CCD camera) over Frenzel glasses (F Glasses) for the observation of spontaneous nystagmus, the incidence and direction of nystagmus, and the frequency, amplitude and slow phase of spontaneous nystagmus., Methods: One hundred vertiginous patients, fifty-three females and forty-seven males participated in this study. Before undergoing routine neurotological examination, their eye movements were recorded by electronystagmogram (ENG) in conjunction with observations of eye movements under F glasses and through an IR-CCD camera. The data was collected from patients who exhibited spontaneous nystagmus either under F glasses or the IR-CCD camera., Results: Thirty-three patients showed spontaneous nystagmus under F glasses. On the other hand, under the IR-CCD camera, all patients examined exhibited spontaneous nystagmus. The frequency of nystagmus was not significantly different between these two systems. However, the amplitude and slow phase velocity exhibited significantly larger values under the IR-CCD camera in patients with spontaneous nystagmus both under the IR-CCD camera and F glasses., Conclusion: From these observations and evidence, the IR-CCD camera can be recommended as a more useful system and powerful tool for neurotological examination than F glasses.

The 85 kDa cytosolic phospholipase A2 (cPLA2) plays a key role in the production of arachidonic acid and lysophospholipids, the precursors of eicosanoids and platelet-activating factor. Here we report the cloning of the promoter of the human cPLA2 gene. A 5.7 kb EcoRI fragment containing the most 5' region of the cPLA2 cDNA was sequenced. The transcription initiation site was identified by rapid amplification of 5'-cDNA ends (5'-RACE) and primer extension analysis. DNA sequence analysis of the 595 base pairs 5' of the transcription start site reveals a 48 base purine-pyrimidine dinucleotide repeat (CA repeat), five interferon-gamma response elements (gamma-IRE), one interferon-gamma activated sequence (GAS) and two glucocorticoid response elements (GRE). The promoter lacks a TATA box. It contains a possible CAAT box at -111 and two octamer binding motifs. The 595 base fragment located immediately upstream of the transcriptional start site exhibited functional promoter activity in transient transfection assays in a bronchial epithelial cell line (BEAS 2B cells). Deletion analysis revealed that the CA repeat may confer an inhibitory effect on the cPLA2 promoter activity. The characterization of the human cPLA2 promoter sequence will allow further studies defining the molecular events regulating the expression of the cPLA2 enzyme, especially the cytokine mediated cPLA2 gene expression.

Following direct KLH antigen challenge to the endolymphatic sac (e. sac) in guinea pigs, degeneration of the cochlea was examined histologically by light microscopy. Degeneration was seen in 21 out of 140 animals presensitized systemically from day 1 to 5 weeks post secondary KLH challenge to the e. sac. Degeneration of the organ of Corti, stria vascularis and spiral ganglion cells was seen from day 1 in 19, 17 and 7 animals, respectively. There was no increase in these degenerative processes during the time course. In the period from day 1 to day 4, severe bleeding in the perilymphatic space occurred simultaneously with cochlear deterioration. Three animals showed perilymphatic fibrosis which was noted after the first week post KLH secondary challenge. In contrast, animals primarily challenged with KLH (locally administered to the e. sac) showed no cochlear degeneration. These results suggest that a locally mounted immune response in the e. sac can cause direct immune injury to cochlear tissues.

The development of endolymphatic hydrops (e. hydrops) following secondary e. sac immune response was investigated in Hartley guinea pigs, for a period of 5 weeks. E. hydrops immediately developed to a maximum from day 2 to day 7 and then gradually reduced in the next 4 weeks. In the e. sac, numerous inflammatory cellular infiltrates, mainly polymorphonuclear cells and macrophages, were seen from day 1 to day 2. Lymphocytes and plasma cells appeared from day 3 and increased to a maximum by day 7 and then gradually decreased in the next 4 weeks. Neither primary e. sac KLH challenge nor e. sac PBS inoculation could derive e. hydrops. Development of e. hydrops was considerably parallel to the grade of immune reaction within the e. sac, suggesting that immuno-pathological reaction of the e. sac has an important effect on regulation of the endolymph volume.

The severity of the regional wall motion and its effects on the global left ventricular diastolic filling were analyzed with use of radionuclide techniques in 19 patients with isolated disease of the left anterior descending coronary artery with previous myocardial infarction. Regional maximum inward movements in the noninfarcted lateral region occurred at a time close to the global end-systole, but occurred far beyond the global end-systole in the infarcted septal and apical regions, resulting in the occurrence of the regional asynchronous wall motion between the infarcted and noninfarcted regions after the global end-systole. A positive correlation between this end-systolic asynchronous wall motion and the asynchronous filling in early diastole was found (r = 0.69, p less than 0.001). A negative correlation between the asynchronous filling in early diastole and the global peak filling rate was also found (r = -0.58, p less than 0.01). Thus, the end-systolic regional asynchronous wall motion causes the subsequent regional asynchronous filling in early diastole, which may cause impairment of the global left ventricular filling in patients with single-vessel coronary artery disease with previous myocardial infarction.

To assess left ventricular (LV) systolic and diastolic function globally and regionally and to study the relationship between regional asynchrony and global LV function in patients with stable effort angina pectoris (AP) without previous myocardial infarction, we conducted a resting gated radionuclide ventriculographic study in 15 control subjects (N group) and 22 AP patients with isolated disease of the left anterior descending coronary artery (LAD). In nine of these 22 AP patients, LV systolic and diastolic function before surgical revascularization (Aorto-Coronary Bypass) were compared with those after surgical revascularization. A computer program subdivided the image of the LV into four regions (septal, basal, lateral and apical) by our previously reported method. The time-activity and first-derivative curves of the global LV and three regions (septal, lateral, apical; the basal region was not computed) LV were computed. In the global LV, the peak filling rate (PFR) normalized to LV end-diastolic volume (EDV) and the ratio of increment of filling volume at 100 msec from global end-systole (ES) to the EDV (%EFV), which was correlated with the time constant of LV pressure decay during isovolumic relaxation, decreased (p less than 0.01, p less than 0.001, respectively) and time to PFR (time interval from global ES to PFR) was greater (p less than 0.001) in the AP group than that in the N group. However, in the AP group, the ejection fraction (EF), normalized peak ejection rate (PFR) and %1/3SV, which was defined as the percent stroke volume ejected during the first third of the global LV ejection phase, were not different from these in the N group.(ABSTRACT TRUNCATED AT 250 WORDS)

Contributions of late diastolic filling (slow filling and atrial systolic phases) to total filling volume in both global and regional left ventricle were analyzed using radionuclide techniques in 21 patients with isolated left anterior descending coronary artery disease without previous myocardial infarction. A computer program subdivided the image of the left ventricle into four regions at a geometric center of the area. The time-activity and its first-derivative curves of the global and regional left ventricles were computed. In the global left ventricle, the percent contributions of late diastolic filling to total filling volume were significantly increased in patients with one-vessel disease than in control subjects (20 +/- 5%, 28 +/- 4%; p less than 0.001). In the regional left ventricle, in patients with one-vessel disease, the percent contributions of late diastolic filling to total filling volume were significantly increased in the septal (25 +/- 5%, 34 +/- 8%; p less than 0.001) and in the apical regions (21 +/- 4%, 28 +/- 4%; p less than 0.001) which were perfused by stenosed vessel. In contrast, there were no significant differences in this value between the two groups in the normally perfused lateral region (22 +/- 6%, 25 +/- 5%; p = NS). These results indicate that the late diastolic filing makes a larger contribution to the left ventricular filling in the affected regions than in the normally perfused regions, and that the increased late diastolic filling in the affected regions are the cause for the increased late diastolic filling in the global left ventricle in patients with one-vessel disease.