Hearing loss (HL) is the most common sensory impairment occurring at birth in developed countries. Epidemiological data show that more than one child in 1000 is born with HL, while more than 50% of prelingual HL cases are found to be hereditary. Approximately 70% of hereditary HL is nonsyndromic and subdivided to autosomal dominant (20%), autosomal recessive (75%), X-linked HL (1%), and maternally-inherited HL associated with the mitochondrial DNA mutation. More than 10 deafness genes have been reported to be responsible for nonsyndromic hereditary HL in Japan. Among them, the most prevalent causative genes, GJB2 and the mitochondrial DNA 12SrRNA are introduced. In addition, this study also refers to the specific genes responsible for the unique audiogram, mainly WFS1 . Finally, the genes related to the enlargement of vestibular aqueduct of inner ear abnormality, SLC26A4, EYA1 and SIX1 are discussed. The clinical and genetic findings associated with these disorders including the results of a recent study are reviewed.

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We report a 24-month-follow-up study of argon plasma coagulation of the inferior turbinate (APC) in patients with perennial nasal allergy. This was a retrospective study, in which 41 patients with perennial allergic rhinitis were treated by inferior turbinate reduction using APC. The grades of nasal stuffiness, rhinorrhea, sneezing and the daily activity impairment caused by these nasal symptoms were evaluated before and then 6, 9, 12, 15, 18, 21, and 24 months after APC, using a questionnaire graded on a four-point scale according to the Severity Criteria of Symptoms of Nasal Allergy issued by the Japanese Society of Allergology. Both nasal stuffiness and any daily activity impairment significantly improved 6 months after APC. Twenty four months after APC, 8/10 (80%) of the patients reported mild or no stuffiness and 9/10 (90%) of the patients reported mild or no daily activity impairement. Neither rhinorrhea nor sneezing were significantly improved during this study. Of the 41 patients 18 (43.9%) received no additional treatment. A second APC treatment was administered to 10/41 (24.4%) patients during follow-up period. Additional conservative medications were needed in 15/41 (36.6%) patients. Among the patients uncontrolled by conservative medical treatment, inferior turbinate reduction using APC provides significant relief in a 24-month-follow-up from nasal stuffiness and daily activity impairment.

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Background-Chronic endemic dental fluorosis is a malformation of teeth caused by excessive ingestion of fluoride during period of tooth development. Apatite crystallites and collagen fibrils determine the caries susceptibility related properties of dentine. Information relating the effect of dental fluorosis with dentine crystallite and collagen structure is currently unavailable. This study examined structural aberrations of apatite crystallites and collagen fibrils in human fluorosed dentine. Method- Superficial dentine of thirty six normal (Thylstrup-Fejerskov index - 0) and thirty six severely fluorosed (Thylstrup-Fejerskov index - 7 to 9) extracted human molars from individuals living in an area which is endemic for dental fluorosis were morphologically analyzed using transmission electron microscopy with selected area electron diffraction and dynamic force microscopy. Results- A statistically significant enlargement in the size of crystallites was found in fluorosed dentine (p<0.05). These crystallites were not homogenously arranged. Selected area electron diffraction revealed a lower density of crystallites in fluorosed dentine. Randomly distributed collagen fibrils showed a less complex lay out in contrast to normal dentine tissue. Conclusion- Ultrastructure aberrations of the dentine explain the caries susceptibility of the tissue and suggest the necessity of special approach in dental caries treatment for patients with chronic severe endemic dental fluorosis.

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Volatile sulfur compounds (VSCs), which are major sources of oral malodor, are produced by putrefactive activities of bacteria. Saliva provides easily degradable protein substrates, and most proteins are glycosylated. We hypothesized that oral malodor would be associated with enhanced proteolysis or deglycosylation in saliva. The purpose of this study was to evaluate properties of glycoproteins in saliva and assess their association with VSC levels. Subjects were 88 patients who visited “the Fresh Breath Clinic”, Dental Hospital, Tokyo Medical and Dental University. They were classified into malodor (n = 67) and non-malodor (n = 21) groups. After collecting saliva, the amounts of the total proteins and carbohydrate were determined. Molecular size distributions of salivary proteins/glycoproteins were analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The amount of the total salivary proteins was significantly higher in the malodor group. Major proteins/glycoproteins observed in SDS-PAGE analyses showed similar distributions between the two groups. In the malodor group, the salivary protein concentrations were positively correlated with the CH₃SH levels (p < 0.05), and the carbohydrate contents were negatively correlated with the H₂S levels (p < 0.05). These results indicated the possibility that salivary proteins/glycoproteins might be related to the malodor generation.

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We have proposed a concept that prolonged rhythmic gum chewing causes a suppressed nociceptive flexion reflex via the serotonergic (5- HT) descending inhibitory pathway. However, the mechanism of activation of the 5-HT system by gum chewing remains undetermined. Several human and animal studies have reported that a direct connection exists between the prefrontal cortex (PFC) and 5-HT neurons in the dorsal raphe nucleus; therefore, we hypothesized that activation of the PFC region might be responsible for augmented 5-HT activity. To evaluate this hypothesis, oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin concentrations in the PFC were measured in the PFC during a 20-min time period of gum chewing using 24-channel nearinfrared spectroscopy. A significant increase in oxyHb level was observed in the ventral part of PFC compared with the dorsal part of PFC. We confirmed the previous results in that the nociceptive flexion reflex was significantly suppressed and the 5-HT level in blood was significantly increased following prolonged gum chewing. These results support the hypothesis that activation of the ventral part of PFC during gum chewing evokes augmented activity of 5-HT neurons in the dorsal raphe nucleus, which in turn suppress nociceptive responses.

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Objectives. The purpose of the present study is to find out the clinical characteristics which determine candidates for tinnitus retraining therapy (TRT) with a sound generator (SG) as well as the prognosis of this treatment. Method. This study enrolled 270 serious tinnitus patients who visited this institute between January 2004 and December 2008 in the TRT program. The relationships among compliance, efficacy, clinical characteristics, and affinity for SG were evaluated retrospectively. Results. The persistence rate at one month was 61.5%. The shorter duration and higher pitch of tinnitus were significant independent predictors of compliance. Six months after the initiation of TRT, 65.2% subjects demonstrated significant relief from tinnitus. The Kaplan-Meier method demonstrated that the overall efficacy rate at 18 months was 86.5%. The lower loudness of tinnitus, recognition of tinnitus attenuation by a sound generator, and patient’s positive attitude toward TRT were significant variables for predicting favorable results. Conclusion. The patients with lower loudness of tinnitus were suitable for TRT with a SG.

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To investigate the adhesion factor of Bacteroides vulgatus derived from ulcerative colitis (UC), we isolated B. vulgatus strains from the large intestinal mucosa of UC patients and non-UC individuals, and examined their adherence to tissue-cultured cells. The adherence to tissuecultured cells in UC-derived strains (36.5 ± 7.9 %) was higher than that in non-UC-derived strains (13.2 ± 7.7 %). PCR and sequencing analysis of outer membrane proteins revealed that the strains derived from five of seven (71.4 %) UC patients had ompA genes belonging to either ompA variant type A or B. The adherence rates in Escherichia coli DH5α transformants with ompA type A variants (33.3 ± 4.6 %) and type B variants (34.6 ± 7.1 %) were higher than the rate in those with non-UC ompA (16.4 ± 4.0 %). Our results suggest that B. vulgatus isolates in the mucosal flora of the large intestine of UC patients have a high frequency of ompA variants and that the variation of ompA variants is one of the factor causing an increase in the adherence of the bacterium.

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To elucidate whether people with hair follicles containing many Propionibacterium acnes cells are prone to acne, we developed a novel method to count the number of P. acnes in hair follicles. We sampled sebaceous material in hair follicles by aspiration at a constant negative pressure from the nose, forehead, and upper arm of 86 patients with acne vulgaris and 209 control subjects with healthy skin, including 84 subjects age-matched to the patients. Genome-equivalents of P. acnes in samples were estimated by real-time quantitative PCR (TaqMan). Numbers of P. acnes genomeequivalents were extremely low in control subjects less than 10 years of age and generally higher at greater ages, with much variation in subjects in the same decade of life. In men, the median count was highest in controls aged 15-19 years; in women, it peaked twice, in controls aged 15-19 years and again in those aged 40 years or older. P. acnes counts on the forehead and nose were higher in the acne patients aged 10-14 years than in the age-matched controls in both sexes. The counts at three sites were similar in acne patients and controls aged 15 to 29 years in both sexes. The results suggest that people with hair follicles containing many P. acnes cells are not particularly prone to acne, except for younger teenagers. Our aspiration method with estimation by real-time PCR can be used to examine the cutaneous microflora of P. acnes.

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Background: To determine the prevalence and clinical features of strabismus in patients with pathologic myopia. Methods: Medical records of a total of 636 highly myopic patients were retrospectively reviewed. Pathologic myopia was defined as spherical equivalent (SE) of at least -8D, or axial length >26.5 mm in patients older than 9 years, <-4D in those younger than 5 years, <-6D in those aged from 6 to 8 years. Myopic refractive degree, axial length measurements, best-corrected visual acuity and eye position were then analyzed. Results: Among 636 patients with pathologic myopia, 520 (81.8%) had orthophoria, 85 (13.4%) had exotropia and 31 (4.9%) had esotropia at near distance. At long distance, 499 (86.5%) had orthophoria, 51 (8.8%) had exotropia and 27 (4.7%) had esotropia. Vertical heterotropia was seen in 103 patients (16.2%). The mean axial length was significantly longer and the mean age was higher in esotropia than orthophoria and in patients with vertical heterotropia than without vertical heterotropia. There were 16 patients with myopic strabismus fixus or acquired progressive esotropia. Conclusions: This study confirmed the relatively high prevalence of horizontal and vertical strabismus in patients with pathologic myopia.

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Schizophrenia is defined by operative diagnostic criteria in DSM-IV with some typical symptoms as hallucinations and duration of the disease. Huber focused on the subjective experience of patients and coined the term “basic symptoms” and created BSABS. Our study investigated the reliability and the diagnostic validity of the 5 clusters of BSABS for DSM-IV-based diagnosis of schizophrenia with a cohort of 105 patients. Good inter-rater reliability was obtained except for one item D.10. As evaluated by Spearman’s rank correlation coefficients, among the 5 clusters excluding Cluster 2, internal consistency was good. This suggests that, although each cluster is heterogeneous, cluster symptoms are the expression of physiological and biological disturbances of schizophrenia. Receiver Operating Characteristic Curve analysis was also used to show the ability of each cluster to discriminate schizophrenia. Results showed that the area representing the powers in discriminate schizophrenia of Cluster 4 “Adynamia”, which is considered related to the dynamic aspect of thinking, was highest, at 0.739. Cluster 1 “Information processing disturbances” which has a predictive ability for schizophrenia showed 0.714 and Cluster 3 “Impaired tolerance to normal stress” showed 0.711. Our findings suggest that, although these clusters symptoms differ from DSM-Ⅳ criteria, they are related to fundamental process of schizophrenia. Use of some of these three clusters with other neurophysiological markers could allow clinical evaluation of schizophrenia from a new perspective.

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In recent years, the increasing number of young people withdrawing from society, so called Hikikomori, has been a cause for concern in Japan. These are people who stay at home and do not work or attend school for more than 6 months. Most of them are not regarded as having any psychotic illness such as schizophrenia. With respect to college students, “student apathy” syndrome has been discussed since the 1960’s. Objectives: To evaluate the proportion of apathetic and withdrawing students among those who leave school, take off, or repeat academic years; to see how these situations have changed in the last 20 years; and to identify the characteristics of such high risk groups so as to provide them with effective psychiatric support services. Methods: First I examined the mean rates of the academic events mentioned above among students of Japanese national universities. I then compared those rates statistically between males and females, and among 6 groups according to gender and academic majors . Then the reasons for those academic events were examined. Results: The rates of each event have continually increased over the last 21 years, and a considerable number of the students were shown to have been in a state of “student apathy.” Male 4-year course students had a high risk, especially male science course students had serious problems.

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BACKGROUND: The effect of multidisciplinary education on clinical decision making by medical students is not well known. METHODS: Twenty of fourth, fifth or sixth year medical students were randomly assigned to multidisciplinary groups (MultiG, n = 7) with two medical, pharmacy and nursing students or medical student groups (MedG, n = 10) with six medical students only and given a two-day PBL program using evidence-based medicine (EBM) methodology. The main outcome measure is clinical decision making by medical students for the case, measured by a 100 mm visual analog scale (VAS). Additional patient information requested and self-evaluation of the PBL program were also measured. RESULTS: Correct answers to assess clinical epidemiology knowledge increased significantly in both groups (4.1 to 9.9 points in MultiG, p < 0.001: 3.6 to 9.7 points in MedG, p = 0.002), while scores at baseline and post-program were not significantly different. The number of additional patient information cards requested was not significantly different (p = 0.10). After the program, the VAS for clinical decision making was significantly different (54 mm and 89 mm, p = 0.013), although preprogram values for both groups were similar. CONCLUSION: Pharmacy and nursing students may have potential to change the clinical decision making by medical students.

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Background: The clinical course of elderly patients with acute myocardial infarction (AMI) can sometimes unexpectedly result in an adverse outcome even when therapy appears to be successful. We suspect that specific factors may characterize this worsening of status during hospitalization. Purpose: This study examines whether the pre-hospital physical activity status of the elderly treated with percutaneous coronary intervention (PCI) for AMI affects their in-hospital course. Methods: We studied 110 consecutive patients, aged 80 or older, who had undergone emergent PCI for AMI. Patients were divided into two groups based on clinical presentation: Better Killip class (Killip classes I and II) and Worse Killip class (Killip classes III and IV). Patients were also divided into two groups based on pre-hospital physical activity status, determined retrospectively by review of medical records: Good physical activity (n =57) comprising those able to go out alone independently and Poor physical activity comprising those mainly confined to home (n =53). Results: The overall in-hospital mortality rate was 9.1% for the study population. The Worse Killip class group had a higher in-hospital mortality rate than the Better Killip class group (27.8% vs 5.4%, respectively; p =0.0102). In addition, the Poor physical activity group had a higher in-hospital mortality rate than the Good physical activity group (15.1% vs. 3.5%, respectively; p =0.047). Conclusion: These data suggest that pre-hospital physical activity status in elderly patients with AMI may affect in-hospital mortality as well as Killip class.

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