Cedar Pollinosis and Mortality: A Population-Based Prospective Cohort Study in Japan.

BACKGROUND: Cedar pollinosis is one of the most prevalent forms of seasonal allergic reaction in Japan. Only one prospective study has examined the association between cedar pollinosis and mortality. Using a symptom-based questionnaire on cedar pollinosis, we investigated the association of cedar pollinosis with all-cause and cause-specific mortality. METHODS: Data came from the Takayama Study, which recruited residents aged ≥35 years in 1992 from Takayama city in Gifu Prefecture, Japan. The current study used information on cedar pollinosis that was obtained from the second survey in 2002. A total of 12,471 persons who were 45-80 years old and had no history of cancer, coronary heart disease, or stroke responded to a questionnaire asking about four symptoms related to cedar pollinosis. Mortality and migration data were obtained throughout the follow-up period up to March 2013. Cox proportional hazard models were used to examine the relation between cedar pollinosis and mortality. RESULTS: A total of 1,276 persons died during follow-up period. Among these, there were 504 neoplasm, 278 cardiovascular, and 181 respiratory deaths. After adjusting for potential confounders, cedar pollinosis was associated with significantly lower all-cause mortality (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.65-0.95) and respiratory mortality (HR 0.38; 95% CI, 0.18-0.82). There was no significant association between cedar pollinosis and mortality due to neoplasm or cardiovascular disease. CONCLUSIONS: We found an inverse association between cedar pollinosis and the risk of all-cause and respiratory mortality. Further research is needed to elucidate the association between cedar pollinosis and mortality.

M2-like macrophage polarization in high lactic acid-producing head and neck cancer.

Reprogramming of glucose metabolism in tumor cells is referred to as the Warburg effect and results in increased lactic acid secretion into the tumor microenvironment. We have previously shown that lactic acid has important roles as a pro-inflammatory and immunosuppressive mediator and promotes tumor progression. In this study, we examined the relationship between the lactic acid concentration and expression of LDHA and GLUT1, which are related to the Warburg effect, in human head and neck squamous cell carcinoma (HNSCC). Tumors expressing lower levels of LDHA and GLUT1 had a higher concentration of lactic acid than those with higher LDHA and GLUT1 expression. Lactic acid also suppressed the expression of LDHA and GLUT1 in vitro. We previously reported that lactic acid enhances expression of an M2 macrophage marker, ARG1, in murine macrophages. Therefore, we investigated the relationship between the lactic acid concentration and polarization of M2 macrophages in HNSCC by measuring the expression of M2 macrophage markers, CSF1R and CD163, normalized using a pan-macrophage marker, CD68. Tumors with lower levels of CD68 showed a higher concentration of lactic acid, whereas those with higher levels of CSF1R showed a significantly higher concentration of lactic acid. A similar tendency was observed for CD163. These results suggest that tumor-secreted lactic acid is linked to the reduction of macrophages in tumors and promotes induction of M2-like macrophage polarization in human HNSCC.

[Eight Cases of Small Cell Neuroendocrine Carcinoma of the Head and Neck].

Small cell neuroendocrine carcinoma of the head and neck is a rarely occurring poorly differentiated and high-grade malignant neoplasm characterized by highly active proliferation of neuroendocrine tumor cells. There are no established therapies for this disease. To clarify the clinical course and develop effective treatment(s) for the carcinoma, we reviewed the data of 8 patients of small cell neuroendocrine carcinoma of the head and neck treated by us between 2006 and 2014 at the Department of Otolaryngology, Gifu University School of Medicine and our affiliated hospitals. The patients consisted of 3 men and 5 women, ranging in age from 38 to 84 years old (mean : 60.9 years). The tumor arose from the nasal cavity or the paranasal sinuses in 3 cases, from the parotid grand in 2 cases, from the oropharynx in 2 cases, and from the hypopharynx in 1 case. The tumor that arose from the hypopharynx was a combined small-cell carcinoma with squamous cell carcinomas, and the one that arose from the oropharynx had already metastasized to the brain. Most of the patients were treated by chemotherapy and radiotherapy based on the treatment employed for small cell carcinoma of the lung. Only the patient in whom the tumor arose from a paranasal sinus was treated by surgery despite the definitive diagnosis of small cell carcinoma. We selected CPT-11 and a platinum agent for 4 patients, and VP-16 and a platinum agent for 3 patients as the first-line chemotherapy. Although two patients showed carcinoma-free survival, one died of recurrence of the regional lymph node metastases and five died of distant metastases despite the absence of locoregional recurrence. The 5-year survival rate was a dismal 25%, suggesting that we need to establish effective treatment(s) for the control of distant metastases in cases of the small cell neuroendocrine carcinoma of the head and neck.

[A case of idiopathic neck bleeding from a parathyroid cyst].

Bleeding from parathyroid cysts is rare. The retropharyngeal space has a very soft structure and if bleeding spreads to this space, airway obstruction can easily occur. We report on a 50-year-old female case with idiopathic neck bleeding from a left parathyroid cyst without any episode of injury. The patient complained of neck swelling after exercise and went to a nearby hospital. At the hospital, the doctor thought this swelling was caused by retropharyngeal bleeding from a tumor behind the left thyroid gland. Embolization of the left thyroid artery was performed. However, the next day, airway obstruction.was occurred and she was brought to our hospital. An emergency operation was performed to open the left neck swelling region. The operation findings and pathological examination showed that the bleeding was caused by a parathyroid cyst and airway obstruction had occurred because of retropharyngeal edema. In this case, the bleeding may have been caused by torsion of the neck when the patient exercised. The retropharyngeal edema probably resulted from the delay of delivery of the lymphatic and venous return and the arterial embolization. 1 year after the operation, the patient is very well and there has been no recurrence.

Effects of high-dose betahistine on intractable dizziness in patients with uncompensated unilateral vestibulopathy.

OBJECTIVE: In the present study, we examined the effects of high-dose betahistine on dizziness handicap inventory (DHI) scores in patients with unilateral vestibulopathy. METHODS: An uncontrolled, open-label, multicenter clinical trial was conducted. Fifteen patients with unilateral vestibulopathy, such as vestibular neuritis, who complained of intractable dizziness for more than three months were enrolled. Initially, all patients were orally administered betahistine at a dose of 36 mg/day for four weeks, which is the standard dose and dosing period for the treatment of dizziness in Japan. The patients were then administered betahistine at a double dose of 72 mg/day for four weeks. Six patients who became aware of the benefits of high-dose betahistine were further administered betahistine at 72 mg/day for an additional 12 weeks (a total of 16 weeks). Perceived disability due to dizziness was assessed by DHI scores. RESULTS: In all 15 patients, short-term administration with high-dose (72 mg/day) betahistine for four weeks, but not low-dose betahistine (36 mg/day) for four weeks significantly decreased DHI scores. In particular, in six responding patients with self-reported benefits after short-term administration with high-dose betahistine, long-term administration with high-dose betahistine for 16 weeks further significantly decreased DHI scores. However, DHI scores of the remaining nine non-responding patients were not changed after short-term administration with high-dose betahistine for four weeks. CONCLUSION: Short-term administration with the standard dose and dosing period of betahistine did not improve DHI scores in the enrolled patients, indicating that they were not compensated for unilateral vestibulopathy with intractable dizziness. The present findings suggest that long-term administration with high-dose betahistine facilitates vestibular compensation to improve intractable dizziness in some, but not all patients with uncompensated unilateral vestibulopathy.

Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity.

The activation of oncogenic signaling pathways induces the reprogramming of glucose metabolism in tumor cells and increases lactic acid secretion into the tumor microenvironment. This is a well-known characteristic of tumor cells, termed the Warburg effect, and is a candidate target for antitumor therapy. Previous reports show that lactic acid secreted by tumor cells is a proinflammatory mediator that activates the IL-23/IL-17 pathway, thereby inducing inflammation, angiogenesis and tissue remodeling. Here, we show that lactic acid, or more specifically the acidification it causes, increases arginase I (ARG1) expression in macrophages to inhibit T-cell proliferation and activation. Accordingly, we hypothesized that counteraction of the immune effects by lactic acid might suppress tumor development. We show that dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinases, targets macrophages to suppress activation of the IL-23/IL-17 pathway and the expression of ARG1 by lactic acid. Furthermore, lactic acid-pretreated macrophages inhibited CD8+ T-cell proliferation, but CD8+ T-cell proliferation was restored when macrophages were pretreated with lactic acid and DCA. DCA treatment decreased ARG1 expression in tumor-infiltrating immune cells and increased the number of IFN-γ-producing CD8+ T cells and NK cells in tumor-bearing mouse spleen. Although DCA treatment alone did not suppress tumor growth, it increased antitumor immunotherapeutic activity of Poly(IC) in both CD8+ T cell- and NK cell-sensitive tumor models. Therefore, DCA acts not only on tumor cells to suppress glycolysis but also on immune cells to improve the immune status modulated by lactic acid and to increase the effectiveness of antitumor immunotherapy.

Association between tinnitus and sleep disorders in the general Japanese population.

OBJECTIVES: There are few studies about the association between tinnitus and sleep disorders in the general population worldwide. This study assessed this association in a Japanese community. METHODS: A total of 14,027 participants 45 to 79 years of age who were in the Takayama Study responded to a self-administered questionnaire about tinnitus and sleep disorders. RESULTS: Of this population, 13.3% of men and 10.6% of women had current tinnitus. The percentages of insomnia, respectively, among individuals with and without tinnitus were 28.1% in men and 36.1% in women and 18.8% in men and 21.5% in women. There were 1.7-fold (95% confidence interval [CI], 1.4 to 2.1) and 1.8-fold (95% CI, 1.5 to 2.2) increases in the odds ratios (ORs) of insomnia for those with tinnitus compared with those without tinnitus in men and women, respectively. Loud or very loud tinnitus was associated with 2.8-fold (95% CI, 1.8 to 4.3) and 3.3-fold (95% CI, 1.9 to 5.6) increases in the OR of insomnia in men and women, respectively. Even low (ie, quiet) or moderate tinnitus was significantly associated with insomnia. Difficulty initiating sleep, difficulty maintaining sleep, and a poor perceived quality of sleep were also significantly associated with tinnitus. CONCLUSIONS: Insomnia and other sleep disorders were significantly associated with tinnitus in Japanese adults.

Evidence for vestibular dysfunction in orthostatic hypotension.

There is little definitive evidence of the clinical significance of the vestibular-cardiovascular reflex in humans, despite the fact that the vestibular system is known to contribute to cardiovascular control in animals. The present study involved 248 dizzy patients (127 male patients and 121 female patients) aged 65 years and younger. We classified all participants into three groups based on their vestibular evoked myogenic potential (VEMP) responses; absent VEMP, asymmetry VEMP and normal VEMP. To investigate the effect of the otolith disorder, which was estimated by the VEMP, on the orthostatic blood pressure responses, the subjects' systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were monitored during the orthostatic test after they actively stood up. The male patients in the absent VEMP group had a significant drop in their DBP at 1 min after active standing up (P < 0.05) without any change in their SBP. Conversely, male patients in the asymmetry VEMP and normal VEMP groups showed a significant increase in the SBP at 1 min after active standing up (P < 0.05). Female patients in the absent VEMP group did not show any significant drop in their blood pressure after standing up (P > 0.05). In the entire group of participants, a total of 19.6% of the patients in the absent VEMP group fulfilled the criteria for orthostatic hypotension (OH), which was significantly > the 8.6% of patients in the normal VEMP group and the 7.2% in the asymmetry VEMP group (P < 0.05). Our results suggest that vestibular disorders due to the dysfunction of otolith organs provoke OH.

Effect of lyophilized powder made from enzymolyzed honeybee larvae on tinnitus-related symptoms, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones.

OBJECTIVES: Tinnitus interferes with sleep and concentration which is associated with depression; however, no drug has been effective in treating tinnitus. Our purpose is to evaluate our hypothesis that the treatment with lyophilized powder of enzymolyzed honeybee larvae as a complementary medicine may provide a therapeutic effect on tinnitus-related symptoms. DESIGN: Sixty tinnitus sufferers participated in a randomized double-blind placebo-controlled trial using the lyophilized powder of enzymolyzed honeybee larvae or a placebo. The Tinnitus Handicap Inventory, a visual analog scale to rate the severity of tinnitus, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones drawn early in the morning were measured upon entry into the study and after 12 wk of follow-up. RESULTS: The lyophilized powder of enzymolyzed honeybee larvae was not superior to placebo with regard to the total score on the Tinnitus Handicap Inventory and the visual analog scale. However, subjects in the honeybee larvae group showed significant improvements in some items about depression associated with tinnitus, whereas subjects in the placebo group showed no improvement in any items. The honeybee larvae group showed significant improvements in the hearing levels at 2 and 4 kHz in the audiogram of the better ear. The intervention of the lyophilized powder of enzymolyzed honeybee larvae was associated with lower serum cortisol levels, serum prolactin levels, and cortisol/dehydroepiandrosterone sulfate ratios. The ratios in the placebo group significantly were increased. CONCLUSIONS: Our results suggest that the lyophilized powder of enzymolyzed honeybee larvae represents an effective complementary medicine to alleviate depression associated with tinnitus by regulating the activity of the hypothalamus-pituitary-adrenal axis.

Effects of aging on lateral stability in quiet stance.

BACKGROUND AND AIMS: Recent studies have demonstrated that assuming the postural corrective torque is regulated by a proportional-integralderivative (PID) controller in the anterior/posterior direction, although few studies have discussed the medial/ lateral (M/L) direction through PID control. Instability in the M/L direction has been reported to be closely related with the risk of falling in the elderly. The purpose of this study is to evaluate the mechanism of postural control in the M/L direction in the elderly. METHODS: The movement of a marker on the subject's back was measured by a CMOS video camera and trunk sway speeds in the M/L direction (TSSX) were calculated as absolute values in whole time series. Using trunk sway data, we identified the gain of PID parameters (proportional gain: KP, integral gain: KI derivative gain: KD). In addition, we calculated the frequency spectrum of trunk sway using the marker locus from 0.016 to 5 Hz by fast Fourier transform. A total of 40 healthy subjects aged from 20 to 85 years old was evaluated with the PID control algorithm in a model of postural control in the M/L direction and their parameter values were estimated. RESULTS: KP significantly increased with age, whereas KD tended to decrease. The TSSX and power ratio of medium frequency (0.2-2.0 Hz) significantly increased with age, but the power ratio of low frequency (0.02-0.2 Hz) tended to decrease. KP and KI were significantly correlated with the power ratio of medium frequency. There was a significant negative correlation between KD and TSSX. CONCLUSIONS: Our results indicate that dependence on hip and ankle stiffness, which may be controlled by proportional gain, increases with age for postural control in the M/L direction. A disability in the feedback mechanism based on velocity information for postural control, which may be associated with derivative gain, tends to increase with age but shows considerable individual variation.

[Surgery in the lateral area of the cervicothoracic border].

Surgery is not usually indicated for the involvement of cervical lymph node metastasis to the subclavian vein. Although surgery is indicated for the involvement of cervical lymph node metastasis to the venous angle, the usual visual field associated with cervical lymph node dissection cannot sufficiently visualize the subclavian vein, and the possibility exists of causing great vessel injury when involved lymph nodes are large and their mobility is restricted. In such cases, surgical excision may be avoided based on the expectation that ligating or cutting the internal jugular vein will be difficult. We examined 10 patients who underwent surgery for the adhesion or invasion of the primary tumor or involved lymph nodes to the venous angle or subclavian vein. The clavicle was removed or displaced to secure the visual field. The sternoclavicular joint was conserved and the clavicle, separated from the first rib, was lifted in 4 patients, while the medial two thirds of the clavicle was removed in 6 patients. Involved lymph nodes could be securely dissected without causing great vessel injury. A chylous leak occurred in one patient undergoing the procedure on the left side.

The relevance of hypothalamus-pituitary-adrenocortical axis-related hormones to the cochlear symptoms in Ménière's disease.

OBJECTIVE: To investigate the association of the HPA (hypothalamus-pituitary-adrenocortical) axis-related hormones with the progression of cochlear symptoms in patients with Ménière's disease. DESIGN: Clinical assessments (Tinnitus Handicap Inventory: THI, visual analog scale to rate the degree of the tinnitus: VAS, hearing levels in pure-tone audiometry) were conducted upon entry into the study (baseline) and at 12 weeks follow-up (week 12). Blood sampling to measure HPA axis-related hormones took place between 9:00 and 10:00 a.m. at baseline and at 12 weeks follow-up. STUDY SAMPLES: This study consisted of 20 unilateral Ménière's disease patients and 21 patients with other diseases with unilateral sensorineural hearing loss and tinnitus. RESULTS: A significant deterioration of the hearing level at high frequency range, especially at 2 kHz, was found during the 12 weeks follow-up in the Ménière's disease group (p < 0.05). The average hearing levels significantly correlated with the serum cortisol level at baseline and week 12 in the Ménière's disease group, especially regarding the high frequency levels (p < 0.01). CONCLUSIONS: Our results suggest that the cortisol levels influence the endolymphatic homeostasis resulting in a deterioration of hearing at high frequency with upstaging of Ménière's disease.

[Superior semicircular canal dehiscence syndrome treated by calcium phosphate cement canal plugging: a case report].

Superior semicircular canal dehiscence (SCD) syndrome exhibits pressure- and/or sound-induced oscillopsia and vertigo due to an absence of bone overlaying the superior semicircular canal. A 33-year-old man with right-ear SCD reported dizziness in a noisy hall three years earlier followed by dizziness during flatulence, straining or coughing, and right-ear autophony. Audiography showed a right-ear low-frequency air-bone gap, with positive Tullio phenomenon and a Valsalva maneuver against closed glottis causing torsional-vertical nystagmus. Temporal-bone computed tomography (CT) led to a diagnosis of right-ear SCD syndrome. Surgical dehiscence plugging with calcium phosphate cement via the middle fossa resolved vestibular and cochlear symptoms in the more than two years since.

Effects of transtympanic intermittent pressure therapy using a new tympanic membrane massage device for intractable Meniere's disease and delayed endolymphatic hydrops: a prospective study.

BACKGROUND: The retrospective study showed that the effect of the middle ear pressure treatment by the tramstympanic membrane massage (TMM) device was similar to that of the Meniett device. OBJECTIVES: The new TMM device named EFET device was prospectively evaluated in patients with Meniere's disease (MD) and delayed endolymphatic hydrops (DEH) and we compared the effects to the Meniett device. MATERIALS AND METHODS: 23 ears of 19 patients were treated with an EFET device, and 17 ears of 15 patients were treated with the Meniett device. All patients suffering from intractable MD and DEH were treated for 4 months. The insertion of a transtympanic ventilation tube was necessary for the Meniett device, but not the EFET device. RESULTS: In patients treated by the EFET and Meniett devices, the frequency of vertigo significantly improved after treatment. The distribution of vertigo outcomes at 4 months after treatment did not differ between patients treated with the both devices. CONCLUSIONS AND SIGNIFICANCE: Middle ear pressure treatment by the EFET device is effective and provides minimally invasive options for intractable MD and DEH like the Meniett device.

The association of the plasma vasopressin level during attacks with a prognosis of Meniere's disease.

An elevation of the plasma arginine vasopressin (AVP) level has frequently been observed in Meniere's disease patients. However, little is known regarding the mechanism behind this elevation. The plasma AVP levels in acute phase were determined in 21 Meniere's disease patients and 16 patients with other types of vertigo. The plasma AVP levels of Meniere's disease patients in the acute phase were significantly higher than in those of other vertigo patients (p < 0.01). In Meniere's disease patients with abnormally high levels of AVP (more than 3.5 pg/ml) in the acute phase, 36% of patients were resistant to conservative treatments for frequent vertigo attacks for the follow-up period of at least 2years. A significant correlation was observed between the plasma AVP in the acute phase and the highest hearing threshold level at a frequency of 1kHz for the follow-up period of at least 1 year (r=0.45, p < 0.05). These results suggest that the elevation in plasma AVP level in the acute phase is associated with the prognosis of Meniere's disease.

The importance of FDG-PET/CT parameters for the assessment of the immune status in advanced HNSCC.

OBJECTIVE: Cancer cells secrete large amounts of lactic acid via aerobic glycolysis. We have shown that lactic acid plays an important role as a proinflammatory and immunosuppressive mediator and promotes tumor progression. Fluorine-18 fluorodeoxyglucose (FDG) uptake detected by positron emission tomography/computed tomography (PET/CT) is considered as a good indicator of aerobic glycolysis in cancer. In this study, we examined the relationships between systemic inflammatory parameters and FDG-PET/CT parameters in advanced head and neck squamous cell carcinoma (HNSCC). Furthermore, we investigated the relationships between FDG-PET/CT parameters and M2-macrophage polarization in HNSCC by assessing the ratio of CD163, a M2-macrophage marker, to CD68, a pan-macrophage marker. METHODS: This study included 73 advanced HNSCC patients. We assessed the C-reactive protein (CRP) level, white blood cell (WBC) count, neutrophil count, lymphocyte count, and monocyte count as systemic inflammatory markers. Additionally, we assessed the maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) as FDG-PET/CT parameters. RESULTS: The CRP level, WBC count, and neutrophil count were correlated with whole-body FDG-PET/CT parameters. The CD163/CD68 ratio was correlated with SUVmax and SUVmean. Our results suggest that systemic inflammation, which is associated with neutrophils, develops in patients with HNSCC having tumors with a larger volume and increased glucose uptake and that M2-macrophage polarization is promoted in HNSCC with increased glucose uptake, SUVmax, and SUVmean. FDG-PET/CT has the potential to reflect cancer-related chronic inflammation and immunosuppressive conditions in cancer patients. CONCLUSIONS: FDG-PET/CT parameters appear to be useful in assessing the immune status in HNSCC.

[Studies on the largest Lyapunov exponents of the standing posture in patients with unilateral vestibular dysfunction].

UNLABELLED: In the present study, we investigated the body sway in patients with unilateral vestibular dysfunction by the largest Lyapunov exponents using a chaotic time series analysis. The largest Lyapunov exponent is regarded as a parameter indexing an orbital instability. MATERIALS AND METHODS: Subjects consisted of 55 normal healthy subjects, 11 patients diagnosed as having vestibular neuritis (VN), 6 patients diagnosed as having sudden deafness (SD) with vertigo, 23 patients diagnosed as having Meniere disease (MD), 11 patients diagnosed as having benign paroxysmal positional vertigo (BPPV) and 14 patients diagnosed as having other vestibular disorders. Using a stabilometer, the sway of the body center of gravity in an upright standing position was recorded with eyes open and closed for 60 seconds under each condition. From the time series data obtained, the largest Lyapunov exponents were calculated using a chaos analysis program. RESULTS: In normal healthy subjects and patients with unilateral vestibular dysfunction, the largest Lyapunov exponents on right-left sway were larger than those on forward-backward sway with eyes open and closed. The largest Lyapunov exponents in patients with unilateral vestibular dysfunction on forward-backward sway with eyes closed were significantly larger than those in normal healthy subjects. A few patients with the instability of standing posture judged from conventional analysis (area of sway, locus length per time) showed higher values of the LLE. We investigated the variation of the values of the largest Lyapunov exponents in patients with unilateral vestibular dysfunction at each stage during recovery from their vestibular damage. The largest Lyapunov exponents at the early stage with stable standing posture were significantly higher than those at the late stable stage with stable standing posture. Some patients at the very early stage had lower values of the largest Lyapunov exponents. CONCLUSION: We speculate that the orbital instability indicated by the values of the largest Lyapunov exponents has a different significance from instability of standing posture indicated by a conventional analysis. We propose that the largest Lyapunov exponents may be an useful subsidiary measure to evaluate postural stability and its change due to vestibular dysfunction.

The Long-Term Efficacy of Cochlear Implantation for Hearing Loss in Muckel-Wells Syndrome.

Muckle-Wells syndrome (MWS), a subclass of cryopyrin-associated periodic syndrome (CAPS), sometimes includes complications of bilateral progressive sensorineural hearing loss. A 48-year-old woman had been diagnosed with pediatric rheumatic arthritis at aged 6 years; however, systematic therapy with prednisolone and methotrexate showed limited efficacy for her general fatigue and arthritic pain, and it never improved the hearing level. She underwent a cochlear implant surgery for progressive profound bilateral hearing loss. After 7 years of cochlear implant surgery, she was diagnosed with MWS by genetic tests. Interleukin (IL)-1ß monoclonal antibody therapy (canakinumab) improved general fatigue and arthritic pain but showed no effect on cochlear symptoms. Owing to successful cochlear implant surgery, she reacquired the hearing and communication function while being able to understand over 90% of monosyllables and words in the sound field of her daily life at 65 dB SPL for the next 13 years of her life. This suggests that peripheral cochlear damage induced by chronic inflammation contributes to the sensorineural hearing loss in cases with MWS, and that cochlear implantation can provide long-term hearing efficacy for patients with MWS with irreversible profound hearing loss.

Involvement of platelet-derived growth factor receptor-beta in maintenance of mesenchyme and sensory epithelium of the neonatal mouse inner ear.

Platelet-derived growth factor receptor (PDGFR) signaling has been demonstrated to play a pivotal role in early embryonic development. Although the expression of PDGF in the inner ear has been studied by RT-PCR, how PDGFR is involved there remains largely unclear. In the current study, we used the antagonistic anti-PDGFR-beta antibody, APB5, to investigate the role of PDGFR-beta in the neonatal mouse inner ear. PDGFR-beta was detected immunohistochemically in the mesenchymal tissue adjacent to the sensory epithelium of the inner ear, and a ligand for PDGFR-beta was detected around the sensory epithelium. To determine whether this expression plays a functional role, we injected APB5 into neonates to block the function of PDGFR-beta. Mesenchymal tissue defects and abnormal capillaries with irregular shapes, especially in the cochlear lateral wall, were detected in APB5-treated mice. The results of a TUNEL assay revealed that not only the adjacent mesenchymal cells but also the sensory epithelial cells underwent cell death. These results indicate that PDGFR-beta signals are required for the survival of the capillary and mesenchymal cells in the neonatal mouse inner ear and also indirectly implicate these signals in the survival of the sensory epithelium.

The orthostatic dysregulation of blood pressure in dizzy patients.

OBJECTIVES: A number of animal studies have confirmed that the otolith organs may contribute to the maintenance of blood pressure during positional change; however, the contribution of such organs remains to be elucidated in humans. METHODS: This study investigated whether acute dizzy patients (n = 11) with an abnormal deviation of the subjective visual vertical (SVV) show an abnormality in the orthostatic regulation of blood pressure in comparison to acute dizzy patients with a normal deviation of the SVV (n = 11) and control subjects (n = 11). RESULTS: The average change in the systolic blood pressure (SBP) at 1 minute after active standing in comparison to that at baseline in dizzy patients with an abnormal deviation of the SVV was -6.8 +/- 3.0 mmHg. The change was significantly lower than that in the control subjects (2.1 +/- 2.6 mmHg, p < 0.05), while the change in dizzy patients with a normal deviation of the SVV (2.6 +/- 2.2 mmHg) was not significantly different from that in the control subjects (p > 0.05). Active standing significantly increased the heart rate (HR) in all participants (p < 0.01) and there was no significant difference in the change of the HR among the 3 groups (p > 0.05). CONCLUSIONS: These results suggest that dizzy patients in the acute phase of recovery from vestibular dysfunction have an orthostatic dysregulation of the blood pressure, thus resulting in such patients suffering from orthostatic intolerance.