Evaluation of changes in endolymphatic hydrops volume after medical treatments for Meniere's disease using 3D magnetic resonance imaging.

OBJECTIVE: To elucidate the relationship between vertigo and EH volume after medical treatment, we investigated changes in endolymphatic hydrops (EH) volume using inner ear magnetic resonance imaging (ieMRI) in relation to clinical results for vertigo and hearing after administration of the anti-vertiginous medications betahistine, adenosine triphosphate (ATP), isosorbide (ISO), and saireito (SAI) for Meniere's disease (MD). METHODS: We retrospectively enrolled 202 consecutive patients diagnosed with unilateral MD from 2015 to 2021 and assigned them to four groups: Group I (G-I), symptomatic oral medication with betahistine only (CONT); Group II (G-II), inner ear vasoactive oral medication (ATP); Group III (G-III), osmotic diuretic oral medication (ISO); and Group IV (G-IV), kampo oral medication (SAI). In total, 172 patients completed the planned one-year-follow-up, which included the assessment of vertigo frequency, hearing improvement, and changes in EH using ieMRI (G-I, n=40; G-II, n=42; G-III, n=44; G-IV, n=46). We constructed 3D MRI images semi-automatically and fused the 3D images of the total fluid space (TFS) of the inner ear and endolymphatic space (ELS). After fusing the images, we calculated the volume ratios of the TFS and ELS (ELS ratios). RESULTS: One year after treatment, vertigo was controlled with zero episodes per month in 57.5% (23/40) of patients in G-I, 78.6% (33/42) in G-II, 81.8% (36/44) in G-III, and 82.6% (38/46) in G-IV (statistical significance: G-I 10 dB in 5.0% (2/40) of patients in G-I, 16.7% (7/42) in G-II, 18.2% (8/44) in G-III, and 21.7% (10/46) in G-IV (statistical significance: G-I=G-II=G-III=G-IV). ELS ratios were significantly reduced after treatment only in the vestibule for G-II, G-III, and G-IV when compared with G-I. Especially among patients with complete control of vertigo after treatment, ELS ratios were significantly reduced after treatment in the vestibule and total inner ear for G-II; in the cochlea, vestibule, and total inner ear for G-III; and in the cochlea, vestibule, and total inner ear for G-IV compared with G-I. However, there were no significant findings in the relationship between hearing results and changes in ELS ratios. CONCLUSION: These results indicate that daily administration of anti-vertiginous medications including ATP, ISO, and SAI could be an effective treatment option for patients with MD at an early stage before it becomes intractable. Treatments to reduce EH might offer better control of vertigo rather than improve hearing.

Behavioral and Immunohistochemical Evidence for Suppressive Effects of Goshajinkigan on Salicylate-Induced Tinnitus in Rats.

Many people are affected by tinnitus, a sensation of ringing in the ear despite the absence of external sound. Goshajinkigan (GJG) is one of the formulations of Japanese traditional herbal medicine and is prescribed for the palliative treatment of patients with tinnitus. Although GJG is clinically effective in these patients, its behavioral effects and the underlying neuroanatomical substrate have not been modeled in animals. We modeled tinnitus using salicylate-treated rats, demonstrated the effectiveness of GJG on tinnitus, and examined the underlying neuronal substrate with c-Fos expression. Intraperitoneal injection of sodium salicylate (400 mg/kg) into rats for three consecutive days significantly increased false positive scores, which were used to assess tinnitus behavior. When GJG was orally administered one hour after each salicylate injection, the increase in tinnitus behavior was suppressed. The analysis of c-Fos expression in auditory-related brain areas revealed that GJG significantly reduced the salicylate-induced increase in the number of c-Fos-expressing cells in the auditory cortices, inferior colliculus, and dorsal cochlear nucleus. These results suggest a suppressive effect of GJG on salicylate-induced tinnitus in animal models.

Word Categorization of Vowel Durational Changes in Speech-Modulated Bone-Conducted Ultrasound.

Ultrasound can deliver speech information when it is amplitude-modulated with speech and presented via bone conduction. This speech-modulated bone-conducted ultrasound (SM-BCU) can also transmit prosodic information. However, there is insufficient research on the recognition of vowel duration in SM-BCU. The aim of this study was to investigate the categorization of vowel durational changes in SM-BCU using a behavioral test. Eight Japanese-speaking participants with normal hearing participated in a forced-choice behavioral task to discriminate between "hato" (pigeon) and "haato" (heart). Speech signal stimuli were presented in seven duration grades from 220 ms to 340 ms. The threshold at which 50% of responses were "haato" was calculated and compared for air-conducted audible sound (ACAS) and SM-BCU. The boundary width was also evaluated. Although the SM-BCU threshold (mean: 274.6 ms) was significantly longer than the ACAS threshold (mean: 269.6 ms), there were no differences in boundary width. These results suggest that SM-BCU can deliver prosodic information about vowel duration with a similar difference limen to that of ACAS in normal hearing.

Perception Mechanism of Bone-Conducted Ultrasound and Its Clinical Use.

It is generally believed that ultrasound cannot be heard. However, ultrasound is audible when it is presented through bone conduction. Bone-conducted ultrasound (BCU) has unique characteristics; the most interesting is its perception in patients with profound deafness. Some patients can perceive it and discriminate speech-modulated BCU. Previous reports have suggested that BCU can be used for a hearing aid or tinnitus sound therapy. In this review, the perception of BCU at both the peripheral and central levels was investigated based on previous studies, although some of them remain controversial. We also investigated the clinical use of BCU. To develop hearing aids utilizing BCU, the encoding of speech signals into BCU has to be established. The outcomes of the reported speech modulations were evaluated. Furthermore, the suppression of tinnitus by BCU was reviewed, and the feasibility of the application of BCU to tinnitus treatment was investigated.

Retrospective evaluation of secondary effects of hearing aids for tinnitus therapy in patients with hearing loss.

OBJECTIVE: Acoustic therapies including hearing aids and tinnitus control instruments are widely used in Japan but without high levels of evidence. The outpatient hearing aid clinic at our institution fits patients with hearing aids and instructs patients on how to use them to control tinnitus if present. In this study, we examined the effects of this approach on tinnitus. METHODS: One hundred and eleven of 138 patients who visited our hearing aid clinic from April 2016 to September 2018 purchased hearing aids after fitting. Sixty-six of these patients (31 men, 35 women; mean age 78.0 ± 8.0 years) had both hearing loss and tinnitus and were enrolled. The tinnitus was bilateral in 41 patients and unilateral in 25 (poor hearing ear, n = 16, good hearing ear, n = 9). Hearing aids were worn bilaterally by 23 patients and unilaterally by 43 (89 devices). Seventeen of the 23 patients wearing bilateral hearing aids had bilateral tinnitus and 6 had unilateral tinnitus, i.e., in 40 ears, the tinnitus side matched the hearing aid side (40 devices) and in 6 ears did not (6 devices). Twenty-four of 43 patients wearing unilateral hearing aids had bilateral tinnitus, meaning that in 24 ears the tinnitus side matched the hearing aid side (24 devices). In six of the remaining 19 cases with unilateral tinnitus, the hearing aid and tinnitus were on the same side (6 devices) and in 13 were on opposite sides (13 devices). Changes in the Tinnitus Handicap Inventory (THI), visual analog scale (VAS, for tinnitus discomfort, severity, and persistence), and Hospital Anxiety and Depression Scale scores were measured immediately before using a hearing aid and 12 months later. RESULTS: Significant effects of hearing aids on tinnitus were observed in all subjects (THI, p = 0.0000030), VAS (severity, p = 0.000000066; discomfort, p = 0.0000013). Significant effects were observed with bilateral hearing aids (THI, p = 0.0012; VAS for severity, p = 0.00069; VAS for discomfort, p = 0.00052) and with unilateral hearing aids (THI, p = 0.00055; VAS for severity, p = 0.000034; VAS for discomfort, p = 0.00007). Spearman's rank correlation coefficient showed a significant positive correlation between the THI and VAS scores (p = 0.0033). In cases of bilateral tinnitus, significant differences were observed with bilateral hearing aids (THI, p = 0.011; VAS for severity, p = 0.0019; VAS for discomfort; p = 0.020) and with unilateral hearing aids (THI, p = 0.00069; VAS for severity, p = 0.00071; VAS for discomfort, p = 0.000093). CONCLUSION: Acoustic therapy using hearing aids was effective for tinnitus. Even when bilateral, a unilateral hearing aid is able to improve tinnitus. When unilateral, the ipsilateral hearing aid is able to improve tinnitus.

Ménière's disease with unremitting floating sensation is associated with canal paresis, gravity-sensitive dysfunction, mental illness, and bilaterality.

OBJECTIVE: The aim of the present study was to evaluate the association of neuro-otological examination, blood tests, and scoring questionnaire data with treatment-resistant intractability of persistent dizziness in Ménière's disease. METHODS: We managed 1520 successive vertigo/dizziness patients at the Vertigo/Dizziness Center in Nara Medical University from May 2014 to April 2018. Five hundred and twenty-two patients were diagnosed with Ménière's disease (522/1520; 34.3%) according to the 2015 diagnostic guideline of the International Classification of Vestibular Disorders. Among the patients with Ménière's disease there were 102 with intractable rotatory vertigo attacks for more than 3-6 months (102/522; 19.5%), including 20 bilateral cases (20/102; 19.6%), and 88 with intractable unremitting floating sensation rather than rotatory vertigo attacks for more than 3-6 months (88/522; 16.9%), including 28 bilateral cases (28/88; 31.8%). Sixty out of 88 cases with intractable unremitting floating sensation were unilateral and were enrolled for hospitalization to undergo neuro-otological examinations including pure-tone audiometry (PTA), the caloric test (C-test), vestibular evoked cervical myogenic potentials (cVEMP), subjective visual vertical (SVV) test, glycerol test (G-test), electrocochleogram (ECoG), inner ear magnetic resonance imaging (ieMRI), blood tests including anti-diuretic hormone (ADH) and bone alkaline phosphatase (BAP), and self-rating questionnaires of depression score (SDS). Data are presented as positive (+) ratios of the number of patients with examination and questionnaire data outside of the normal range. RESULTS: The ratios (+) were as follows: C-test=33.3% (20/60), cVEMP=25.0% (15/60), SVV=50.0% (30/60), G-test=55.0% (33/60), ECoG=63.3% (38/60), ieMRI=86.7% (52/60), ADH=35.0% (21/60), BAP=11.7% (7/60), and SDS=40.0% (24/60). Multivariate regression analysis revealed that the periods of persistent dizziness were significantly longer in unilateral Ménière's patients with C-test(+), SVV(+), and SDS(+) compared with those with negative findings. Additionally, the periods in bilateral cases were significantly longer than those in unilateral ones. CONCLUSIONS: Although approximately 70% of patients with Ménière's disease are usually treatable through the appropriate conservative medical therapy, the presence of canal paresis, gravity-sensitive dysfunction, neurosis/depression, and bilaterality may make the persistent dizziness intractable and may thus require additional treatments.

Temporal window of integration estimated by omission in bone-conducted ultrasound.

Bone-conducted ultrasound (BCU) can be heard for both normal-hearing and some profoundly deaf individuals. Moreover, amplitude-modulated BCU can transmit the speech signal. These characteristics of BCU provide the possibility of the developing a bone-conducted ultrasonic hearing aid. Previous studies on the perception mechanism of speech-modulated BCU have pointed to the importance of temporal rather than frequency information. In order to elucidate the perception of speech-modulated BCU, further investigation is need concerning the processing of temporal information. The temporal processing of air-conducted audible sounds (ACASs) involves the integration of closely presented sounds into a single information unit. The long-temporal window of integration was estimated approximately 150-200 ms, which contribute to the discrimination of speech sound. The present study investigated the long-temporal integration system for BCU evaluated by stimulus omission using magnetoencephalography. Eight participants with normal hearing took part in this study. Ultrasonic tone burst with the duration of 50 ms and frequency of 30 kHz was used as the standard stimulus and presented with steady onset-to-onset times or stimulus-onset asynchronies (SOAs). In each sequence, the duration of the SOAs were set to 100, 125, 150, 175, 200, or 350 ms. For deviant, tones were randomly omitted from the stimulus train. Definite mismatch fields were elicited by sound omission in the stimulus train with an SOA of 100-150 ms, but weren't with an SOA of 200 and 350 ms for all participants. We found that stimulus train for BCUs can be integrated within a temporal window of integration with an SOA of 100-150 ms, but are regarded as a separate event when the SOA is 200 or 350 ms in duration. Therefore, we demonstrated that the long-temporal window of integration for BCUs estimated by omission was 150-200 ms, which was similar to that for ACAS (Yabe et al. NeuroReport 8 (1997) 1971-1974 and Psychophysiology. 35 (1998) 615-619). These findings contribute to the elucidation and improvement of the perception of speech-modulated BCU.

A Two-Year Randomized Trial of Interventions to Decrease Stress Hormone Vasopressin Production in Patients with Meniere's Disease-A Pilot Study.

UNLABELLED: Meniere's disease, a common inner ear condition, has an incidence of 15-50 per 100,000. Because mental/physical stress and subsequent increase in the stress hormone vasopressin supposedly trigger Meniere's disease, we set a pilot study to seek new therapeutic interventions, namely management of vasopressin secretion, to treat this disease. We enrolled 297 definite Meniere's patients from 2010 to 2012 in a randomized-controlled and open-label trial, assigning Group-I (control) traditional oral medication, Group-II abundant water intake, Group-III tympanic ventilation tubes and Group-IV sleeping in darkness. Two hundred sixty-three patients completed the planned 2-year-follow-up, which included assessment of vertigo, hearing, plasma vasopressin concentrations and changes in stress/psychological factors. At 2 years, vertigo was completely controlled in 54.3% of patients in Group-I, 81.4% in Group-II, 84.1% in Group-III, and 80.0% in Group-IV (statistically I < II = III = IV). Hearing was improved in 7.1% of patients in Group-I, 35.7% in Group-II, 34.9% in Group-III, and 31.7% in Group-IV (statistically I < II = III = IV). Plasma vasopressin concentrations decreased more in Groups-II, -III, and -IV than in Groups-I (statistically I < II = III = IV), although patients' stress/psychological factors had not changed. Physicians have focused on stress management for Meniere's disease. However, avoidance of stress is unrealistic for patients who live in demanding social environments. Our findings in this pilot study suggest that interventions to decrease vasopressin secretion by abundant water intake, tympanic ventilation tubes and sleeping in darkness is feasible in treating Meniere's disease, even though these therapies did not alter reported mental/physical stress levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099046.

Negative prognostic factors for psychological conditions in patients with audiovestibular diseases.

OBJECTIVE: To examine the backgrounds of patients with audiovestibular disease regarding what influences their psychological state. METHODS: During a 12-year period, 375 successive patients with audiovestibular diseases were enrolled in this study. Diseases included unilateral (n=174) and bilateral (n=51) Menière's disease, sudden deafness with vertigo (n=70), and vestibular neuritis (n=80). Diagnosis, sex, age, duration of disease, vertigo frequency, persistent nystagmus, and ipsilateral/contralateral hearing levels were recorded. Cornell Medical Index (domains III-IV=neurosis) and Self-Rating Depression Scale (score>40=depression) were applied during acute vertigo remissions in all patients. RESULTS: Neurosis and depression, respectively, were diagnosed in 62.7% and 82.4% of bilateral Menière's, 32.7% and 48.9% of unilateral Menière's, 15.7% and 38.6% of sudden deafness/vertigo, and 12.7% and 31.3% of vestibular neuritis patients. Multivariable logistic regression analysis showed that Menière's disease with longer disease duration (Oz 1.212; P=0.021) and worse hearing in the secondary affected ear (Oz 1.131; P=0.042); sudden deafness/vertigo with persistent nystagmus (Oz 1.895; P=0.005); and vestibular neuritis with longer disease duration (Oz 1.422; P=0.019) and persistent nystagmus (Oz 1.950; P=0.0003) had mental illness significantly more often than those with shorter-duration disease, better hearing and no persistent nystagmus. CONCLUSION: Mental disorder increased in accordance with solo vertigo, vertigo/hearing loss, repeated symptoms, and bilateral lesions. Treatment strategies should be carefully constructed for patients with persistent nystagmus, long disease duration, and hearing loss in the secondary affected ear to avoid psychological disorders.

Surgical results and psychological status in patients with intractable Ménière's disease.

OBJECTIVES: Mental disorder is often one of the causes to make treatments for Ménière's disease more difficult. The aim in the present study is to examine ratios of the neurosis and depression in patients with intractable Ménière's disease and also relationships between the ratios and surgical results after endolymphatic sac drainage with large doses of steroids. METHODS: Between 1998 and 2009, we enrolled 263 intractable Ménière's patients and divided into two groups, 207 in surgical group and 56 in non-surgical group. We used the Cornell Medical Index (CMI) and the Self-rating Depression Scale (SDS) at the diagnosis in our hospital to evaluate their psychological condition before treatments. CMI domains III and IV were defined as neurosis and SDS scores more than 40 as depression as a matter of convenience. Two years as well as seven years after surgery, patients with vertigo zero/month and hearing change>-10dB were evaluated in success group and the others in non-success group. RESULTS: Neurosis and depression were diagnosed in approximately 40% and 60%, respectively, of intractable Ménière's disease. Our results showed that surgical treatment significantly improved vertigo suppression and hearing gain in patients with no psychological symptoms compared with those exhibiting psychological symptoms both in surgical and non-surgical groups. Furthermore, surgical results in cases with mental disorder were superior to non-surgical results in cases without mental distress. CONCLUSIONS: All taken together, psychological supports could be necessary for improving results both in the surgical and non-surgical treatments for patients with intractable Ménière's disease. Some cases with intractable Ménière's disease should really require additional surgical treatments even after psychological therapies.

Aberrant keratin 7 and 20 expression in triple-negative carcinoma of the breast.

Early studies characterizing the keratin (K) profile of various epithelial tissues indicated that breast carcinoma is K7 positive and K20 negative, but not all breast carcinomas show this profile. Triple-negative carcinoma (TNC) has been characterized by negativity for estrogen receptor (ER), progesterone receptor (PgR), and Her2/neu protein. TNC is more likely to metastasize to the viscera and present as a metastatic poorly different carcinoma. In our study, on the basis of immunohistochemical staining of ER, PgR, and Her2/neu, 75 of the 290 patients with invasive breast carcinoma were judged to have TNC. K20 expression was detected in 6 of 75 patients with TNC, and non-TNC was negative in all 215 cases (P = .0003). K7 expression was also detected in 72 of 75 TNC cases. However, non-TNC was negative in 26 of 215 cases, which was significant (P = .0457). An aberrant profile of K was observed in the TNC group, indicating that caution is needed in determining the site of primary tumors using immunohistochemical algorithms. It should be kept in mind that patients with TNC show highly variable K profiles in practical diagnosis.

Cytopathological features of mammary analogue secretory carcinoma--review of literature.

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that morphologically resembles mammary secretory carcinoma and carries the identical ETV6-NTRK3 fusion gene. We report a surgical resected case of MASC in the parotid gland of a 41-year-old man. The cytological smears of a preoperative fine-needle aspiration showed many sheets and crowded clusters of monotonous epithelioid cells with mild atypia, suggestive of monomorphic tumor. Histologically, the tumor was composed of cuboidal cells with follicular, tubular, and solid structures, reminiscent of acinic cell carcinoma of follicular variant, which had been previously classified. This case had ETV6-NTRK3 fusion gene transcript confirmed by fluorescence in situ hybridization and reverse transcription polymerase chain reaction. In the cytological and histopathological diagnosis of monomorphic tumor of salivary gland, MASC needs to be taken into consideration as a differential diagnosis. Further immunohistochemical and gene analyses are needed in diagnosis of MASC.

Breast cancer screening and the changing population pyramid of Japan.

BACKGROUND: Breast cancer has been the most prevalent cancer in Japan since the 1990s. The mortality from breast cancer is increasing in Japan, whereas in other industrialized countries it has been decreasing since 1990. On the other hand, Japan faces unparalleled growth in its aging population. The aim of this study was to report the mammography screening among Japanese women and the related upcoming changes in the population pyramid of Japan. DATA SOURCES AND METHODS: The reference data for our study were obtained from the Center for Cancer Control and Information Services, Japan Ministry of Internal Affairs and Communications, Ministry of Health, Labour and Welfare, the Japanese Cancer Society, and the National Institute of Population and Social Security. The survey data were obtained from breast cancer and mammography screenings in the Tokyo Prefecture in 2008. The following parameters were analyzed: annual breast cancer incidence, current screening rates, average life-span, and predicted demographic statistics. RESULTS: Our results showed that breast cancer incidence and mortality have been increasing annually in Japan. The average age of breast cancer patients increased to 58.40 years in 2010. The incidence of breast cancer in women aged 65 years and older increased from 25.3 to 32.9 % in the last 10 years and is expected to continue to increase in the future. The check-up rate was 16.0-20.0 % for women aged 65-74 years and 43.0-46.0 % for women aged 40-54 years. According to our questionnaire survey, concerns about breast cancer and mammography screening were high in the young and low in the elderly women. The Japanese population aged 65 years and older was 30,740 (24.1 %) in 2012 and is estimated to increase by 40 % over the next 20 years despite Japan's declining population size. CONCLUSION: Breast cancer incidence has increased in Japan, even among patients aged 65 years and older. Breast cancer has become increasingly prevalent in older Japanese women. As the population pyramid of Japan changes, women aged 65 years and older, who think that there is no longer need to receive mammography screening and are not educated regarding self-examinations, should be encouraged to receive regular check-ups for breast cancer.

An examination of the effects of broadband air-conduction masker on the speech intelligibility of speech-modulated bone-conduction ultrasound.

Ultrasound can be heard by bone-conduction, and speech-modulated bone-conducted ultrasound (BCU) delivers the speech information to the human ear. One of the recognition mechanisms is the demodulation of the signals. Because some of the profoundly deaf can also hear speech-modulated BCU, another mechanism may also contribution to the recognition of speech-modulated BCU. In this study, eight volunteers with normal hearing participated. The intelligibilities of speech-modulated BCU were measured using a numeral word list under masking conditions. Because the masker can mask the demodulated sounds, the evaluation of the masking reveals the contribution of the demodulation to the recognition of speech-modulated BCU. In the current results, the masking of speech-modulated BCU differed from that of original non-modulated speech. Although the masking shifted the recognition curve for the original speech upward, the same results were not observed for the speech-modulated BCU. The masking generated the difference in the correct answers among the words for the speech-modulated BCU. The current results suggested the importance of the envelope of the modulated ultrasonic signal to the recognition under masking condition. Both demodulation and direct ultrasonic stimulation contribute to the recognition of speech-modulated BCU for the normal hearing individuals, and the direct ultrasonic stimulation plays an important role in the recognition for the profoundly deaf.

Residual inhibition of tinnitus induced by 30-kHz bone-conducted ultrasound.

Sounds at frequencies of >24-kHz are classified as ultrasound which cannot be heard by humans if presented by air conduction, but can be perceived if presented by bone conduction. Some research studies involving ultrasonic hearing have reported that tinnitus is masked by bone-conducted ultrasound (BCU). However, little is known about residual inhibition (RI), which is a continuous reduction or disappearance of tinnitus after presentation of BCU. This study investigated whether RI could be induced by BCU. Five types of the masker sounds were used to measure RI in 21 subjects with tinnitus. A bone-conducted 30-kHz pure tone was used as a BCU, and an air-conducted 4-kHz pure tone, narrow-band noise, white noise, and a bone-conducted 4-kHz pure tone were used as controls of audible sounds. The masker intensities of the 30-kHz BCU and audible sounds were set at the minimum masking levels of tinnitus plus 3 and 10 dB, respectively, considering the narrow dynamic range of BCU. The duration of RI induced by the 30-kHz BCU was significantly longer than those induced by the 4-kHz sounds, but was not significantly different from that induced by the white noise. BCU activates the cochlear basal turn in response to the high frequency, which may broadly overlap with the frequency range that included the dominant tinnitus pitch in most of our subjects. The longer RI duration for the 30-kHz BCU was probably derived from this characteristic. These results suggested that the peripheral stimulation characteristic of BCU probably contributed to inducing long RI durations.

Evaluation of prosodic and segmental change in speech-modulated bone-conducted ultrasound by mismatch fields.

Speech-modulated bone-conducted ultrasound (BCU) can transmit speech sounds for some profoundly deaf individuals. Hearing aids using BCU are considered to be a novel hearing system for such individuals. In our previous study, the speech discrimination for speech-modulated BCU was objectively confirmed using a magnetoencephalography. Moreover, in our previous behavioral study, prosodic information for speech-modulated BCU could also be discriminated in the normal hearing. However, the prosodic discrimination for speech-modulated BCU has not objectively been studied. In order to evaluate the prosodic discrimination for speech-modulated BCU, mismatch fields (MMFs) elicited by prosodic and segmental change were measured for speech-modulated BCU and air-conducted speech. Ten Japanese participants with normal hearing took part in this study. Stimuli re-synthesized from the speech of a native Japanese female adult were used. Standard stimulus was /itta/ with a flat pitch pattern, and two deviant stimuli were /itta?/ with a rising pitch pattern and /itte/ with a flat pitch pattern. All and nine participants elicited the prominent MMF elicited by the prosodic and segmental change for the speech-modulated BCU, respectively. The moment of MMF components for speech-modulated BCU was significantly smaller than those for air-conducted speech, while no difference in the MMF latency elicited by the prosodic and segmental change were observed between both stimulus conditions. Comparing the MMFs elicited by prosodic and segmental change, no significant differences were observed for both stimulus conditions. Thus, it is suggested that the prosodic change can be discriminate to the same degree as segmental change even for speech-modulated BCU. However, discrimination capability for speech-modulated BCU is slightly inferior to that for air-conducted speech.

Phase II clinical trial of high-dose toremifene as primary hormone therapy in aromatase inhibitor-resistant breast cancer.

BACKGROUND: Third-generation aromatase inhibitors(AIs)are now common in adjuvant hormone therapy for breast cancer in postmenopausal women. However, a suitable treatment has yet to be established for patients who develop cancer recurrence during or after adjuvant AI therapy. PATIENTS AND METHODS: This prospective study evaluated the efficacy and safety of 120mg/day toremifene citrate(TOR-120)administered orally to 23 patients with recurrent breast cancer who were receiving or had received adjuvant AI therapy. Primary therapy for recurrence was TOR-120 monotherapy. RESULTS: The response rate was 13. 0%(partial response: three patients), the clinical benefit rate was 78. 3%(partial response: three patients; long-term stable disease: 15 patients), and median time to progression was 8. 1 months. Grade 1 adverse events such as loss of appetite, sweating, flushing and edema face were observed. CONCLUSION: TOR-120 monotherapy was effective and safe as a primary hormone therapy for recurrent breast cancer unresponsive to AIs.

Human ultrasonic hearing is induced by a direct ultrasonic stimulation of the cochlea.

Ultrasound can be perceived by bone-conduction. The cochlear basal turn is involved in processing bone-conducted ultrasound (BCU) information. Previous studies have suggested that ultrasonic perception is induced by ultrasound itself. In contrast, it has also been suggested that a lower frequency sound is generated in non-linear process during the transmission pathway to the cochlea to induce an auditory sensations. To address this issue, we assessed cisplatin-induced changes in BCU sensitivity at 27, 30 and 33kHz in 20 participants (40 ears) who were scheduled to undergo cisplatin chemoradiation therapy. Following the treatment, 62.5% ears were diagnosed with hearing loss according to the criteria of the American Speech-Language-Hearing Association. As expected, significant increases in sensitivity threshold were observed for air-conducted sounds ranging from 8 to 14kHz. In contrast, the BCU threshold significantly decreased after the treatment. Considering that both air-conducted high-frequency sound and BCU are perceived in the cochlear basal turn, these findings indicate that ultrasonic perception is independent of hearing a lower frequency sound generated in non-linear process. In addition, our findings support the hypothesis that ultrasound itself induces ultrasonic perception in the cochlea. The observed cisplatin-induced increase in BCU sensitivity may be explained by hypersensitivity associated with outer hair cells' disorder.

[A case of repeated bone metastases of breast carcinoma successfully treated by S-1 chemotherapy].

We report a case of breast carcinoma with repeated recurrences in the right bone. The recurrent site of the bone was treated by radiation therapy with a total of 3 7. 5 Gy irradiation, and chemotherapy with the CMF regimen. After 2 years, recurrence was suspected in the same region because there was an elevation of the NCC-ST-439 tumor marker. We carried out chemotherapy with S-1 100mg/body/day. The NCC-ST-439 value returned to within the normal range after 3 months' administration of S -1, and continued in the normal value for 20 months.

Duration-dependent growth of N1m for speech-modulated bone-conducted ultrasound.

Bone-conducted ultrasound (BCU) modulated by speech sound is recognized as speech sound and activates the auditory cortex similar to audible sound. To investigate the mechanisms of perception, the effects of stimulus duration on N1m were compared among air-conducted audible speech sound (AC speech), AC speech with carrier BCU and speech-modulated BCU in eight native Japanese with normal hearing. The Japanese vowel sound /a/ was used as a stimulus with durations of 10, 15, 20, 30, 40 and 60 ms. Comparison between AC speech with and without carrier showed that the presentation of carrier had no effect on N1m evoked by AC speech. Comparison among the three conditions showed that N1m amplitude for speech-modulated BCU differed from that for the two AC speeches. Moreover, N1m amplitude growth saturated at 40 ms for speech-modulated BCU, and at 20 ms for two AC speeches. These results suggest a difference in temporal integration of N1m between speech-modulated BCU and AC speech. Considering these results, it is reasonable to conclude that N1m evoked by speech-modulated BCU is influenced mainly by the ultrasonic component rather than demodulated audible sound. Given this finding, the notion needs to be considered that the mechanisms underlying perception and recognition of speech-modulated BCU depend on the ultrasonic component to some extent.