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Aspergillus-induced mycotic aneurysm is difficult to treat and often has poor outcomes with severe symptom progression. Early diagnosis is also difficult, and blood and cerebrospinal fluid tests often fail to reveal any findings. A 74-year-old man presented with recurrent nosebleeds in addition to symptoms of left optic neuritis. Contrast-enhanced computed tomography scan revealed a left internal carotid artery pseudoaneurysm protruding into the left Onodi cells, which was identified as the origin of bleeding. Endovascular left internal carotid artery occlusion was performed. One month postoperatively, external ophthalmoplegia and disorientation occurred. Although antibiotic treatment was continued for 1 month, consciousness loss and haematemesis occurred, and a new contralateral right internal carotid artery pseudoaneurysm ruptured, which resulted in death. At autopsy, Aspergillus infection centred on the skull base was pathologically found, although the sinus mucosal surface was normal. This case suggested a mycotic infection secondary to optic neuritis resulted in a left infectious pseudoaneurysm that spreads to the skull base and formed an aneurysm on the contralateral side 4 months thereafter. Therefore, the possibility that features of the Onodi cells contributed to the spread of inflammation inside and outside the skull and were involved in the formation of aneurysms inside and outside the dura mater was considered for the first time. [ABSTRACT FROM AUTHOR]

Pharmacological lung volume reduction in COPD is an important goal in treatment with long-acting bronchodilators because in addition to airflow limitation, lung hyperinflation considerably affects COPD symptoms. Quantitative computed tomography (CT) simultaneously provides structural information about airway dimensions, emphysematous changes, and lung volumes, some of which are difficult to be evaluated by pulmonary function. Here, we evaluated changes in CT parameters and pulmonary function in 30 patients with COPD who underwent CT scans before and one year after starting tiotropium treatment and in 12 patients with COPD who were not treated with long-acting bronchodilators. Baseline pulmonary function and CT parameters did not differ between the two groups. One-year tiotropium therapy improved physiological-indices including residual volume (RV) and ratio of RV to total lung capacity (RV/TLC) (−235 mL, p = 0.005, and −2.9%, p = 0.0001, respectively), and CT-indices including wall area percent (WA%) and inner luminal area in right upper lobe apical and lower lobe basal segmental bronchi (−1.59%, p = 0.01, 2.27 mm2, p = 0.0005; and −1.33%, p = 0.0008, 3.42 mm2, p < 0.0001, respectively), low attenuation volume (LAV) and total lung volume (CT-TLV) (−92 mL, p = 0.0003, and −211 mL, p = 0.002, respectively). Changes in LAV, CT-TLV, RV, and RV/TLC were significantly greater in the tiotropium, than the non-bronchodilator group. The tiotropium-induced reduction in LAV correlated with the decrease in RV (ρ = 0.45, p = 0.01). Our findings not only indicate the value of the comprehensive CT measurements in assessing the effects of bronchodilators, including pharmacological lung volume reduction, but also further understanding of the structural changes underlying physiological improvements induced by bronchodilators. [ABSTRACT FROM AUTHOR]

Background: COPD pathology involves not only the lungs but also extrapulmonary abnormalities. Osteoporosis is one of the most important abnormalities because it may cause vertebral compression fractures and deteriorate pulmonary function. COPD patients have many risk factors for osteoporosis, such as low BMI, decreased activity, systemic inflammation, and use of corticosteroids. Some of these factors have been shown to deteriorate with COPD exacerbations. We previously demonstrated the correlation between emphysema and osteoporosis and between emphysema progression and COPD exacerbations. Thus, the hypothesis that exacerbation causes osteoporosis progression in COPD patients was investigated. Methods: Forty-two COPD patients not on osteoporosis treatment for over 2 years were recruited. During follow-up, exacerbations had been prospectively recorded. Thoracic vertebral bone mineral density (BMD) was measured using chest CT, and the annual change in BMD was calculated. The change was compared between patients with and without a history of exacerbations. Results: The decrease in thoracic vertebral BMD was greater in patients with than in those without a history of exacerbations (median ΔBMD mg/ml⋅year: -3.78 versus -0.30, p = 0.02). Moreover, multivariate regression analysis showed that exacerbations and baseline PaO2 were independent predictors of the BMD decrease (R2 = 0.20, p = 0.007, and R2 = 0.09, p = 0.03, respectively) after adjustment for baseline age, smoking status, and airflow limitation. Conclusions: This is the first longitudinal study to demonstrate that COPD exacerbations are independently associated with osteoporosis progression. Osteoporosis progression should be evaluated in COPD patients, especially in those with a history of frequent exacerbations. [ABSTRACT FROM AUTHOR]

Background: We recently reported that hypoxia-inducible factor 1α (HIF-1α), HIF-2α and cyclooxygenase 2 naked DNA induced angiogenesis in a rat indirect bypass model. In this work, we investigated whether the collateral circulation induced by HIF-1α DNA affected the cerebral infarction. Methods: We utilized a rat encephalomyosynangiosis (EMS) model and inoculated HIF-1α DNA onto the brain surface. These treatments were performed before the cerebral infarction occurred. We thereafter performed middle cerebral artery occlusion on the fifth or tenth day after EMS. Results: A histological section treated with HIF-1α DNA for 10 days showed a well-developed collateral circulation (p<0.05) and a reduction in the infarction volume in comparison to the control DNA (p<0.01). Conclusion: These results suggest the feasibility of a novel approach for the treatment of cerebral ischemia via the development of therapeutic collateral circulation, in which neovascularization may be indirectly achieved using a transcriptional regulatory strategy. [ABSTRACT FROM AUTHOR]

Conclusions: The characteristic of both the vertical-torsional positional nystagmus with long time constant and its disappearance at the neutral head position could diagnose cupulolithiasis in posterior semicircular canal (PSCC) in the eight patients with the PSCC type of benign paroxysmal positional vertigo (P-BPPV). Objective: The aim of the study was to diagnose cupulolithiasis in patients with P-BPPV. Patients and methods: We used three-dimensional rotation axis analysis of nystagmus of the vertical-torsional positional nystagmus in 111 patients with P-BPPV and evaluated its time constant. We then examined whether the vertical-torsional positional nystagmus with long time constant disappeared at the neutral head position where the axis of the heavy cupula of the affected PSCC is aligned with gravity. Results: The first parameter showed a wide variation that could be divided into two groups: one lasting more than 40 s in 8 patients and another below 20 s in 103 patients. Since the time constant of the positional nystagmus induced by cupulolithiasis was much longer than that induced by canalolithiasis, this finding suggests that cupulolithiasis in the PSCC induced the vertical-torsional positional nystagmus with a long time constant in the group of eight patients. The vertical-torsional positional nystagmus disappeared in these patients at the neutral head position, where the axis of the cupula of affected PSCC aligned with gravity. [ABSTRACT FROM AUTHOR]

Conclusion: This study demonstrated differential gene expression profiles along the axis of the mouse cochlea. It also suggests the mechanism that establishes the tonotopic organization. Objectives: The molecular basis of the tonotopic mapping of the mammalian cochlea remains unclear. We therefore examined the genes that were abundantly expressed in either the apex or the base of mouse cochlea. Materials and methods: Apical and basal portions of cochlea, which contained the organ of Corti and spiral ganglion neurons, were independently dissected from 10 adult C57BL/6 mice, and their total RNAs were respectively isolated. The gene expression profiles of each of these two pools were examined and compared to each other by the complementary DNA microarray technique. Results: Of 20 289 probes tested, 64 genes were found to be expressed in the apical portion more than fivefold more abundantly than in the basal portion, and 77 genes were vice versa. Of interest, the genes of several functional proteins such as β2- and γ2-subunits of GABAA receptors dominated the basal part, indicating that these molecules may be involved in high-frequency tuning of the hair cells and/or ganglion neurons. [ABSTRACT FROM AUTHOR]

Conclusion. The incidence of new cases of Meniere's disease (MD) in elderly patients aged 60 years or more was found to have increased over time after correction for age distribution in the overall population. Job- and care-related fatigue may be involved in the recent increase in elderly-onset cases because physical and mental fatigue can induce onset of the disease. Objectives. Changes over time in the epidemiologic characteristics of MD in Japan were analyzed. Materials and methods. Between 1975 and 2006, four nationwide, multi-center surveys of MD were conducted by the Meniere's Disease Research Committee of Japan (1975-1976) and the Peripheral Vestibular Disorders Research Committee of Japan (1982-1984, 1990, and 2001-2006). Information was collected by the committee members on a total of 1368 de novo cases of definite MD, 520 reported in the first survey, 290 in the second survey, 148 in the third survey, and 410 in the fourth survey. Results. Clear changes were seen over time in the population-adjusted sex distribution of the disease and population-adjusted age at onset. The number of definite MD cases in females increased over time relative to the number of cases in males. The proportion of cases in which onset occurred at 60 years of age or more increased over time when the number of cases in each age group was adjusted for changes in age distribution of the population over time. From the time of the third survey, there was a slight increase in the proportion of cases with bilateral involvement. [ABSTRACT FROM AUTHOR]

Conclusion. Fine-needle aspiration cytology (FNAC) is the diagnostic modality of first choice for characterization of parotid mass lesions, while magnetic resonance imaging (MRI) should not be requested routinely. MRI can be reserved until FNAC shows the indication for surgical intervention. Objectives. Although both FNAC and MRI are useful preoperative diagnostic modalities for parotid mass lesions, it is not well established which modality is more effective. In the present study we sought to address the relative value of FNAC and MRI in relation to the differential diagnosis of benign and malignant parotid mass lesions. Subjects and methods. Eighty-one patients with parotid mass lesions (60 benign and 21 malignant) who had preoperatively undergone FNAC and MRI were reviewed retrospectively. Results. Unsharp margin and infiltration into adjacent tissues on MRI significantly correlated with a malignant histology. The sensitivity/specificity/accuracy of FNAC and MRI were 90%/95%/94% and 81%/92%/89%, respectively. Either FNAC or MRI served equally to predict the malignant nature of parotid mass lesions. Furthermore, the combination of FNAC and MRI yielded no diagnostic advantage over either modality alone. Accurate histological typing rates by FNAC were 80% and 62% for benign and malignant lesions, respectively. [ABSTRACT FROM AUTHOR]

This study investigated the effects of adaptive dynamic range optimization (ADRO®) processing for six bimodal listeners who used a hearing aid in one ear and a cochlear implant in the other. 'Bimodal' refers to the use of acoustic and electrical stimulation together. Bimodal speech recognition thresholds with the Japanese hearing in noise test were significantly lower for two ADRO devices than two non-ADRO devices in quiet, in noise from the front, and in noise from the implanted side. When the noise was presented from the non-implanted side there was no significant difference between the ADRO and non-ADRO conditions. The hearing aid measure of contrast questionnaire indicated that participants preferred ADRO in 77.3% of situations. ADRO was especially preferred in more difficult situations. The ADRO processing was designed for use in bimodal prostheses, and this study confirmed that speech intelligibility and sound quality improvements are obtainable by using ADRO in a bimodal context. [ABSTRACT FROM AUTHOR]

Conclusions. Two patients showing two rotational axes of their positional nystagmus had canalolithiasis in bilateral posterior semicircular canals (PSCCs), leading to the diagnosis of true bilateral benign paroxysmal positional nystagmus (P-BPPN). Another 18 patients had a single rotation axis of their positional nystagmus with short time constant (TC) on one side and long TC on the other. Since canalolithiasis in the uppermost PSCC may be transient cupulolithiasis, evoking positional nystagmus with long TC, the diagnosis of the latter patients should be pseudo-bilateral P-BPPN. Objective. To differentiate the true bilateral posterior canal type of P-BPPN from pseudo-bilateral P-BPPN. Patients and methods. The rotational axis and TC of positional nystagmus were three-dimensionally analyzed in 20 patients showing geotropic torsional nystagmus on the left and right Dix-Hallpike (D-H) maneuvers. Results. Two patients showed two rotational axes of their positional nystagmus, which were perpendicular to the plane of the PSCCs. There were no differences in TCs of their positional nystagmus between bilateral D-Hs. Another 18 patients showed a single rotational axis of their positional nystagmus, which was perpendicular to the plane of either the left or right PSCC. TCs of their positional nystagmus were short on one side and long on the other. [ABSTRACT FROM AUTHOR]

Changes in slow phase eye velocity (SPEV) and time constant (TC) of benign paroxysmal positional nystagmus in horizontal canal type were examined at transitional period from cupulolithiasis (apogeotropic nystagmus) into canalolithiasis (geotropic nystagmus) in two patients. SPEV and TC of positional nystagmus were tri-dimensionally analyzed. The first patient showed an apogeotropic nystagmus. Head rotation to the left in supine position induced a right-beating nystagmus with an initial SPEV of 15.3°/s and a TC of 133 s. The nystagmus then gradually declined with a TC of 31.3 s after reaching a maximum SPEV of 28.8°/s. After the nystagmus disappeared, he showed a geotropic nystagmus. The second patient showed a left-beating nystagmus with an initial SPEV of 2.5°/s and a TC of 141 s when his head was rotated to the right in supine position. The nystagmus then gradually declined with a TC of 8.05 s after reaching a maximum SPEV of 16.7°/s. After the nystagmus disappeared, he showed a geotropic nystagmus. The present findings suggested that in both patients, at the period of an increase of SPEV of the positional nystagmus with the shortening of its TC, cupulolithiasis transformed into canalolithiasis. [ABSTRACT FROM AUTHOR]

Relapsing polychondritis (RP) is characterized by inflammation and subsequent degeneration of cartilage. We report a 61-year-old woman who had RP with audio-vestibular manifestations. She was also diagnosed as having a myelofibrosis with myeloid metaplasia (MMM). Bilateral endolymphatic hydrops (EH) was confirmed by dominant –SP/AP of the electrocochleogram (ECochG). When thalidomide and prednisolone were prescribed for the treatment of MMM, symptoms of RP – including the inner ear dysfunction – were ameliorated. Isosorbide, one of the osmotic diuretics commonly used for the treatment of Meniere's disease (MD) in Japan, was also effective in keeping her free from inner ear dysfunction. This is the first report to confirm the existence of EH in a patient with RP with audio-vestibular manifestations. We suppose that an immunological imbalance due to MMM, in conjunction with a specific immunogenetic background, may have played a role in the pathogenesis of RP and the formation of EH in this patient. [ABSTRACT FROM AUTHOR]

When diagnosing and treating patients with acute vertigo, the clinician must differentiate brain lesions from benign peripheral disorders. We here report a rare case of acute vertigo caused by intracranial vertebral artery dissection mimicking peripheral disease. A 67-year-old man presented with spontaneous nystagmus and moderate ataxia preceded by neck pain. No other neurological signs were observed, suggesting acute peripheral vertigo. However, magnetic resonance imaging (MRI) demonstrated a cerebellar infarction. Simultaneous magnetic resonance angiography (MRA) showed no flow void of the left vertebral artery and contrast-enhanced MRA demonstrated a double lumen sign, suggesting that vertebral artery dissection was a cause of infarction. The clinical course was favorable without anticoagulation drugs, which are sometimes contraindicated because of the potential risk of subarachnoid hemorrhage. Vertebral artery dissection can cause cerebellar infarction in patients without vascular risk factors mimicking acute peripheral vertigo. Careful history regarding the neck pain is important and MRA in combination with MRI can replace angiography in diagnosing this disorder. [ABSTRACT FROM AUTHOR]

Objectives To assess the dynamics of the vertical semicircular canal (VSCC)-ocular reflex in normal subjects and then to compare their gain in VSCC-ocular reflex with that of patients with benign paroxysmal positional vertigo (BPPV). Material and Methods Subjects were sinusoidally rotated around the earth-vertical axis with their head tilted 60° backward and turned 45° to the right or left side from the sagittal plane at frequencies of 0.1, 0.3, 0.5, 0.7 and 1.0 Hz with a maximum angular velocity of 50°/s. Head rotation to the right side on the right anterior semicircular canal (SCC)-left posterior SCC plane or to the left side on the left anterior SCC--right posterior SCC plane stimulated the pair of VSCCs. Eye movements were recorded on a video imaging system with an infrared charge-coupled device camera, using our new technique for analyzing the rotation vector of eye movements in three dimensions. Results The mean gains in left posterior SCC-ocular reflex in normal subjects ranged from 0.44 at 0.1 Hz to 0.79 at 1.0 Hz, while the mean gains in right anterior SCC-ocular reflex ranged from 0.45 at 0.1 Hz to 0.73 at 1.0 Hz. The mean gains in right posterior SCC-ocular reflex in normal subjects ranged from 0.53 at 0.1 Hz to 0.89 at 1.0 Hz, while the mean gains in left anterior SCC-ocular reflex ranged from 0.53 at 0.1 Hz to 0.88 at 1.0 Hz. Thus, the gains in VSCC-ocular reflex did not differ among the four VSCCs in normal subjects. Similarly, vestibulo-ocular reflex (VOR) gains of the four VSCCs in patients with right- or left-sided BPPV were almost the same at all frequencies compared to those of normal subjects. Conclusion In patients with BPPV, gains in VOR in the four VSCCs were not changed in comparison with those of normal subjects. It is suggested that the mass of free-floating otoconial debris associated with canalolithiasis was too small compared to that of the endolymph to change the canal dynamics. [ABSTRACT FROM AUTHOR]

Objectives Universal newborn hearing screening (UNHS) is considered beneficial and is accepted worldwide. However, some problems remain, and administrative systematization has yet to be established in many countries. This study assessed the hearing screening of referred newborn infants and discusses the problems that remain. Materials and methods Over the two years from July 2001 to June 2003, 98 ears of 49 infants were judged as a "referral" from a newborn hearing screening program, and were subsequently referred to our hospital for further examination using conventional ABR and other audiological tests. The methodology used for hearing screening varied between practitioners and hospitals that utilized both different recording apparatus for AABR and/or automated DPOAEs and independent protocols. Results Conventional ABR identified 21 infants with bilateral normal hearing, 12 with unilateral hearing loss, and 16 with bilateral hearing loss, and a total correspondence rate of 40.8% (20 out of 49 infants). In a comparative analysis, 26 ears out of 98 (26.5%) were determined as false-positive, seven out of 98 as false-negative (7.1%), and there was a total correspondence rate of 66.3% (65 out of 98 ears). Five of the seven false-negative cases who were referred with unilateral hearing loss exhibited moderate to profound bilateral hearing loss (moderate; one infant, severe to profound; four infants). Of the 16 infants with bilateral hearing loss, nine with more than moderate loss had hearing aids fitted at our hospital or related educational institution before most were six months old. Conclusions Our results suggest the accuracy of newborn hearing screening remains an issue, but may be improved by an experienced examiner and better protocols including a two-stage process and altered timing of screening. Other ongoing health care programs need to monitor for signs of hearing loss even in the "passed" infants because of possible false-negatives and delayed-onset hearing loss. Improvement is needed in both the intervention systems and diagnostic follow-up of hospitals. Early public support is also required for infants with either severe to profound or moderate hearing loss. From the viewpoint of test conditions and puerperal parental psychological problems, it is considered that the timing of screening needs further discussion. Here it is suggested that screening should be performed within the first three months of infant's life but not be limited to before hospital discharge, and incorporated into the routine health care program for one-month-old infants without reducing efficiency. [ABSTRACT FROM AUTHOR]

The aquaporins (AQPs) are a family of small transmembrane water transporters. It has recently been revealed that they play a role in regulating homeostasis in the inner ear fluids. Steroid therapy is usually administered to patients with inner ear disorders; however, the mechanism of steroid effects has not been clearly determined. To elucidate the points of action of steroids in the inner ear, we recently examined the distributions of AQP isoform mRNAs in the rat inner ear and identified AQP1-6 mRNAs in the rat cochlea and AQP1, 3, 4, 5 and 6 mRNAs in the rat endolymphatic sac by means of reverse transcriptase polymerase chain reaction (PCR). In this study, we investigated changes in expression of AQP mRNAs in the rat inner ear after i.p. injections of steroids using real-time quantitative PCR and found that AQP3 mRNA in the endolymphatic sac was significantly upregulated in both dose- and time-dependent manners. This result suggests that steroids may effect water homeostasis in the rat inner ear via AQPs. [ABSTRACT FROM AUTHOR]

Objective To assess the advantages of binaural hearing for cochlear implant (CI) users using a hearing aid (HA) for the contralateral ear. Material and Methods The subjects comprised 3 males and 3 females (age range 48-84 years). All of them had been using a CI and HA for>6 months. Their speech perception was examined in quiet using monosyllables and Japanese Hearing in Noise Test (J-HINT) sentences. Speech perception in noise was examined using J-HINT sentences. Late cortical waves were measured while subjects listened to 1 kHz frequent and 2 kHz target tone stimuli. The latency of the event-related potential (P300) wave was compared for monaural and binaural hearing conditions. Results Three subjects showed significantly better results for binaural than monaural (CI alone) hearing for monosyllables and HINT sentences ( p <0.05; paired t -test). Subjects with better speech perception had been using an HA for longer than those with poor performance (18.3 vs 4.0 years). The overall average score was better for binaural than monaural hearing in the speech perception test under quiet and noisy conditions. Comparison of the latency of the P300 wave under monaural and binaural hearing conditions showed a significantly shorter latency for the latter ( p =0.02; paired t -test). Conclusions Although the use of an HA alone showed marginal benefit for CI users, binaural hearing (CI+HA) resulted in a significant improvement in speech perception under various circumstances. [ABSTRACT FROM AUTHOR]

In order to elucidate the role of the vestibulocerebellar neural circuits during two-stage bilateral labyrinthectomy (BL) we examined Fos-like immunoreactive (-LIR) neurons as a marker of neural activation in the rat brainstem after BL and the projections of these neurons into the vestibulocerebellum using retrograde tracing and immunohistochemical techniques. Simultaneous BL did not show any Fos expression in the medial vestibular nucleus (MVe). However, with an interval of >6 h between the two stages of BL, Fos-LIR neurons were induced in the ipsilateral (ipsi-) MVe of the side operated on second, partially projecting into the ipsi-vestibulocerebellum. A previous study demonstrated that some of the unilateral labyrinthectomy-induced Fos-LIR neurons in the ipsi-MVe projected into the ipsi-vestibulocerebellum and inhibited the contra-MVe neurons, resulting in the restoration of the right-left balance. Taken together with our present data, it is suggested that some of the labyrinthectomy-induced Fos expression in the ipsi-MVe is representative of a switch-on signal for the vestibulo-cerebello-vestibular inhibitory neural circuits, which remain turned off after symmetrical lesions such as simultaneous BL but are turned on after severe asymmetrical lesions in order to restore the balance. [ABSTRACT FROM AUTHOR]

Although steroid treatment is generally administered for patients with inner ear disorders, including Ménière's disease, the mechanism via which steroids exert their effects remains to be clarified. The aquaporins (AQPs) are a family of small transmembrane water transporters, and it has recently been revealed that they play a role in regulating homeostasis in the inner ear fluids. In order to elucidate the action points of steroids in the inner ear, we firstly identified AQP1, 2, 3, 4, 5 and 6 mRNAs in the rat cochlea and AQP1, 3, 4, 5 and 6 in the rat endolymphatic sac by means of reverse transcription-polymerase chain reaction. Subsequently, we found that intratympanic injections of steroids upregulated AQP1 mRNA of the rat cochlea in a dose-dependent manner. These results suggest that steroids may affect water homeostasis in the rat inner ear mainly via AQP1. [ABSTRACT FROM AUTHOR]

The purpose of this study was to clarify the role of the vestibular system in human locomotion. The subjects were nine healthy controls, nine patients with unilateral vestibular deficiency (UVD) and nine patients with bilateral vestibular deficiency (BVD). The UVD subjects were Ménière's disease patients who were being treated with administration of gentamicin into the tympanic cavity. BVD subjects were hearing-impaired individuals who showed no response to the ice-water caloric test. A total of 13 markers were attached to the head, trunk (C7), hip and foot in order to measure translational and rotational motions with the aid of a video image processing system. All subjects were instructed to restrict their stride length to 80 cm while walking on a treadmill and watching a visual target. However, walking speed varied depending on the ability of the subject to maintain body equilibrium. The results showed that walking speed and step frequency were significantly lower for the UVD and BVD groups than for the normal group. Analysis of head movements in the sagittal plane showed a counteracting motion between pitch rotations and vertical translation as previously reported. We also found head counteracting motions between yaw rotation and lateral translation in the horizontal plane. These mechanisms are thought to help stabilize the gaze during walking. When the head fixation point was calculated by projecting the naso-occipital axis line during walking, the head counteracting motion was found to assist the vestibulo-ocular reflex in stabilizing the gaze. In addition, normal subjects seemed to use head stabilization as a space strategy in order to minimize head yaw movement. In contrast, UVD and BVD subjects adopted head stabilization as a trunk strategy. [ABSTRACT FROM AUTHOR]

In this study, vestibular caloric stimulation (CS) inhibited noradrenergic (NA) neurons of the locus coeruleus (LC) in rats. The vestibular input can be modified by the ventrolateral medulla (VLM), which then inhibits the LC neuronal activity via GABA[sub A] receptors. Clinically, CS induces vertigo in humans. Thus, LC-NA inhibition may be involved in the development of vertigo. Moreover, it is speculated that Sopite syndrome, one of the major symptom complexes of motion sickness, is also evoked by LC-NA inhibition. The central LC-NA neuronal system may participate in vertigo and motion sickness independent of the histaminergic neuronal system. In contrast, the cholinergic neuronal system may mediate LC-NA inhibition during the vestibulo-autonomic reflex. The LC-NA system projects to most higher centers and affects sensory information processing. Therefore, it is suggested that the suppression of sensory information processing induced by LC-NA inhibition causes drowsiness, one of the major symptoms of vertigo and motion sickness. It is also speculated that LC-NA inhibition participates in the development of sensory mismatch during vertigo and motion sickness. [ABSTRACT FROM AUTHOR]

We examined the effects of amygdala lesion (AL) or hippocampal lesion (HL) on hypergravity-induced motion sickness in rats. Rats do not vomit, but the behavior known as pica, the eating of non-nutritive substances such as kaolin, can be used as an index of motion sickness. In the present study, hypergravity-induced kaolin intake and apomorphine-induced kaolin intake were measured before and after brain lesions. After AL, hypergravity-induced kaolin intake and the ratio of the hypergravity- to apomorphine-induced kaolin intakes were decreased. These results indicate that AL suppressed motion sickness more than pica behavior itself, suggesting that the amygdala plays an important role in the development of motion sickness in rats. Conversely, after HL, hypergravity-induced kaolin intake was increased, as was the ratio of the hypergravity- to apomorphine-induced kaolin intakes. These results indicate that HL aggravates motion sickness induced by hypergravity in rats, suggesting that the hippocampus counteracts motion sickness. [ABSTRACT FROM AUTHOR]

In this study in order to elucidate the role of the flocculus in the whole process of vestibular compensation from the very early stage to the chronic stage, we first examined unilateral labyrinthectomy (UL)-induced spontaneous nystagmus (SN), a behavioral marker of vestibular compensation, and Fos expression, a marker of neural activity, in the vestibular brainstem in pre-unilateral flocculectomized (pre-UF) rats. UL in pre-UF rats caused more severe vestibulo-ocular deficits at the very early stage than it did in floccular-intact rats. Fos expression occurred in the medial vestibular nucleus contralateral to the UL side (contra-MVe) and the prepositus hypoglossal nucleus ipsilateral to the UL side (ipsi-PrH), whereas Fos expression was never seen after UL in floccular-intact rats. Therefore, these findings suggest the UL in pre-UF rats activates the contra-MVe and ipsi-PrH neurons and causes great imbalance between intervestibular nuclear activities, inducing more severe vestibular symptoms at the very early stage than those in floccular-intact rats. Next, we observed MK801 (a specific antagonist on the NMDA receptor)-induced SN in pre-UF rats at the chronic stage after UL. MK801 administration to pre-UL rats caused reappearance of SN even 14 days after UL, while administration to floccular-intact rats at a post-UL interval of 14 days never induced decompensation. Therefore, these findings suggest that the flocculus takes part in NMDA receptor-mediated neural circuits involved in vestibular compensation and modifies the neural interactions at the chronic stage after UL. Taken together, those results suggest that the flocculus plays important roles in the restoration of a balance between intervestibular nuclear activities, to reduce vestibular symptoms during the very early stage, and thereafter in the modification of NMDA receptor-mediated neural interactions in the central vestibular system at the chronic stage. [ABSTRACT FROM AUTHOR]

The accuracy of radiological examinations has improved and their diagnostic ability has markedly increased. However, the cost of such examinations has also recently become an issue. In this study, the clinical significance of radiological examinations for sensorineural hearing loss (SNHL) was evaluated and the value of their utilization was reconsidered. A total of 1,276 ears of 724 patients who demonstrated unilateral or bilateral SNHL was studied retrospectively. Findings of radiological examinations such as plain X-ray (X-p), computed tomography (CT) and magnetic resonance imaging (MRI) of the brain or the temporal bone were investigated. Temporal bone X-p was usually performed to rule out acoustic tumors (AT). CT was further performed in 119 patients (16.4%) and MRI in 84 patients (11.6%) in total. The reasons or symptoms for further examination such as CT or MRI were X-p findings or auditory symptoms suspicious for AT or vertigo/dizziness suspicious for intracranial disease. Of five cases with AT, two with a small tumor exhibited normal findings for the internal auditory canal on temporal bone X-p. These small ATs were finally confirmed by MRI. MRI could also detect lacunar infarctions, cerebral atrophy and high jugular bulb which might be related to SNHL. These findings confirmed that MRI is very useful for detecting small ATs and suggested that MRI also reveals cerebral vascular insufficiency in patients with SNHL. [ABSTRACT FROM AUTHOR]

In our previous study, caloric stimulation (CS) of the vestibular apparatus inhibited noradrenergic neuronal activity in the locus coeruleus (LC) in urethane-anaesthetized rats. Therefore, the inhibition of LC noradrenergic neurons is involved in vestibulo-autonomic responses. Since motion sickness can be cured by scopolamine, cholinergic neuron system may also be involved in vestibulo-autonomic responses. The present study examined the effects of intracerebroventricular injection of ethylcholine mustard aziridinium ion (AF64A), a presynaptic cholinergic neurotoxin, on CS-induced LC inhibition. In AF64A-treated rats, the CS-induced LC inhibition was less pronounced than in normal rats. In a subsequent series of experiments, the intravenous injection of scopolamine blocked the CS-induced LC inhibition. These findings suggest that central cholinergic neurons are associated with noradrenergic neuronal inhibition during the vestibulo-autonomic reflex. [ABSTRACT FROM AUTHOR]

The importance of the vestibular apparatus in the development of motion sickness is widely accepted, although the role of the vestibular cerebellum remains controversial. We examined the effects of vestibular cerebellum lesion on the development of motion sickness in rats. Rats do not vomit, but the behaviour known as “pica”, the eating of non-nutritive substances, such as kaolin, can be used as an index of motion sickness. A 2 h load of hypergravity induced pica in rats, indicating that they suffered from motion sickness. Pica was induced by hypergravity load even after surgical lesion to the bilateral cerebellar flocculus or to the cerebellar vermis. We concluded that the vestibular cerebellum was not essential in the development of motion sickness in rats. [ABSTRACT FROM AUTHOR]

We investigated the DNA ploidy pattern, cell cycle and the percentage of Ki-67 positive fractions in fresh surgical material from 17 benign and 33 malignant thyroid tumours using flow cytometry. DNA aneuploidy was not seen at all in benign tumours, but was seen in 3 out of 33 malignant tumours, suggesting that detection of DNA aneuploidy indicates malignancy, although the detection sensitivity was low. Regarding the cell cycle, there was no difference in the percentage of S-phase fractions (SPF) or G2 plus M phase fractions (G2M) between benign and malignant tumours. However, the percentage of Ki-67 positive fractions in malignant tumours (39.9±3.9%) was significantly higher than that in benign tumours (9.4±2.1%), indicating that malignant thyroid tumours contained a large population of G1 phase cells. When a cut-off value of 20% was used for Ki-67 positive fractions, sensitivity was 82%, specificity was 88% and accuracy was 84% for the diagnosis of malignant tumours. Although this study was carried out on surgically derived materials, it is possible that flow cytometric analysis of fine needle aspiration-derived materials may have a place in preoperative histopathological assessment of thyroid tumours. [ABSTRACT FROM AUTHOR]

We have developed a new technique for analyzing the rotation vector of eye movement in three dimensions with an infrared CCD camera based on the following four assumptions: i) the eye rotates on a point; ii) the pupil edge is a circle; iii) the distance from the center of eye rotation to pupil circle remains unchanged despite the rotation; iv) the image of the eye by the CCD camera is projected onto a plane which is perpendicular to the camera axis. After taking digital images of voluntary circular eye movements, we first constructed a three-dimensional frame of reference fixed on the orbita of the subject wearing a goggle equipped with an infrared CCD camera, and determined the space coordinates of the center of eye rotation, the center of the pupil, and an iris freckle. We then took digital images of the eye movements during a saccade or vestibulo-ocular reflex (VOR) and analyzed the axis and angle of the eye movements by the trajectories of the center of the pupil and the iris freckle. Finally, Listing's plane of saccade and the gain and the phase of VOR were obtained. The suitability of this technique is examined. [ABSTRACT FROM AUTHOR]

The KS 300 is a multifunctional software image analysis system using an object-oriented programming environment. The possibility of its application for the inner ear was studied by using specimens from humans and squirrel monkeys, immunostained for the brain-derived calcium-binding protein, S-100 protein. Grey images were used for measurements. The cell borders were outlined by hand, using a digitizer. The absolute grey values of the pixels changed when the brightness of the images or other conditions changed. By contrast, the relative grey values, i.e. the absolute grey values correlated to the mean grey values of the histoimage, remained constant. By utilizing these relative grey values, it was possible to compare cells both between different specimens and between different areas within the same specimen. The different grey values of spiral ganglion cells stained for S-100 protein are objective quantitative measurements and are believed to reflect differences in their function. In some regions of both human and squirrel monkey specimens, relatively intensely stained cells predominated, whereas in other regions, relatively weakly stained cells were mainly observed. Thus, our image analysis system using the relative grey values has proved suitable for quantitative analysis of immunostained specimens in order to compare them and to assess cell function. [ABSTRACT FROM AUTHOR]

Sound lateralization and speech discrimination abilities are both closely related to central auditory system function. In this study, we investigated the relationship between sound lateralization and speech discrimination in patients with sensorineural hearing loss (SNHL) of unknown aetiology or presbycusis. Interaural intensity difference (IID) and interaural time difference (ITD) discriminations were measured using a self-recording apparatus for dichotic sound presentation, and the means of bilateral maximum scores in speech discrimination tests were calculated. Subjects with normal sound lateralization had good speech discrimination scores above 70%, while those with abnormal sound lateralization had poor scores below 70%. Some patients, however, had good speech discrimination but abnormal sound lateralization. These findings were obtained in both IID and ITD discrimination tests. Furthermore, some subjects could not discriminate ITD, although all could discriminate IID. These findings suggest that sound lateralization ability may be affected more than speech discrimination in SNHL of unknown aetiology or in presbycusis. [ABSTRACT FROM AUTHOR]

The patterns of change in the growth function of distortion product otoacoustic emissions (DPOAEs) associated with hearing improvement in six patients with Meniere's disease were investigated. The growth functions of 2F1-F2 DPOAEs at F2 frequencies of 1001, 2002 and 4004 Hz (DP-1, DP-2 and DP-4, respectively) were measured with F2 intensities ranging from 70 to 37 dBSPL in 3-dB steps. The F1 intensity was maintained 10 dB higher than the F2 intensity. The growth function was paired with the hearing threshold at the corresponding F2 frequency, and the relationships between changes in DP-1, DP-2 and DP-4 and those in hearing thresholds at 1, 2 and 4 kHz, respectively, were also investigated. The patterns of change in the growth function associated with hearing improvement could be classified into five types. In the first type, the DPOAE growth function became detectable, while the remaining four types were distinguished by combinations of changes in DPOAE amplitudes for lower and higher primary intensities. Multiple parameters, such as maximum amplitude and detection threshold of the growth function, appeared to be required for simple detection and discrimination of these patterns of change. It was also found that the DPOAE growth functions clearly changed in some cases even though the hearing thresholds did not change significantly at the corresponding F2 frequencies. This finding suggests that DPOAE growth function measurement can detect small changes in cochlear function which do not lead to changes in hearing threshold, and has higher sensitivity than pure tone audiometry in monitoring of cochlear function. In conclusion, our findings suggest that measurement of the DPOAE growth function is useful for monitoring cochlear function, and that information on its patterns of change is clinically important and useful. [ABSTRACT FROM AUTHOR]

In previous reports we have shown that caloric stimulation (CS) of the vestibular apparatus inhibits locus coeruleus (LC)-noradrenergic neuronal activity in urethane-anaesthetized rats. The present study examined the effect of neural histamine depletion by α-fluoromethylhistidine (α-FMH) on CS-induced LC inhibition. In α-FMH treated rats, LC neuronal inhibition caused by CS was still observed. This finding indicates that the central histaminergic neuron system does not participate in the CS-induced LC-noradrenergic inhibition. It is suggested that the noradrenergic neuron system is involved in the development of vestibulo-autonomic response, independent of the histaminergic neuron system. [ABSTRACT FROM AUTHOR]

Vestibular compensation consists of two stages: the inhibition of the contralesional medial vestibular nucleus (contra-MVe) activities at the acute stage after unilateral labyrinthectomy (UL) and the recovery and maintenance of the ipsilesional MVe (ipsi-MVe) spontaneous activities at the chronic stage after UL. In this paper, we reviewed molecular mechanisms of vestibular compensation in the central vestibular system using several morphological and pharmacological approaches in rats. Based on our examinations, we propose the following hypotheses: i) at the acute stage after UL, the activated neurons in the ipsi-MVe project their axons into the flocculus to inhibit the contra-MVe neurons via the NMDA receptor, nitric oxide (NO) and/or GABA-mediated signalling, resulting in the restoration of balance between intervestibular nuclear activities. ii) At the chronic stage after UL, the flocculus depresses the inhibitory effects on the ipsi-MVe neurons via protein phosphatase 2A (PP2A) beta, protein kinase C (PKC) and glutamate receptor (GluR) delta-2, to help the recovery and maintenance of ipsi-MVe activities. [ABSTRACT FROM AUTHOR]

To investigate changes in distortion product otoacoustic emissions (DPOAEs) associated with hearing improvement in ears with Meniere's disease, four parameters were studied. These were: DPOAE amplitudes for a moderate (L1/L2=65/55 dBSPL) and a high (L1/L2=74/64 dBSPL) primary level (65/55-DP and 74/64-DP amplitudes, respectively); maximum level of DPOAE amplitudes in the growth function (maximum DP level); and DPOAE detection threshold (DP threshold) of the growth function. Significant correlations were found between all four parameters and hearing threshold, except for the 65/55-DP amplitude at 1 kHz, and each parameter appeared to reflect the hearing threshold to some extent. However, the changes in the four parameters associated with hearing improvement were somewhat complicated. Changes could not be evaluated due to lack of detection of responses when the hearing thresholds exceeded 50 dBHL. Findings that parameters became detectable, the DP amplitude or the maximum DP level increased significantly, or the DP threshold lowered significantly were classified as “improved” findings. The number of ears with “improved” findings was larger for the maximum DP level or the DP threshold than for the 65/55-DP and 74/64-DP amplitudes in ears with a 10 dB or greater improvement in hearing threshold at the corresponding F2 frequency. Furthermore, a significant decrease in amplitude was found in some ears, although the hearing threshold was not elevated when the 65/55- or 74/64-DP amplitude was used as a parameter. On the other hand, “improved” findings for the maximum DP level or the DP threshold were observed for a relatively large number of ears without a significant change in hearing threshold, and it was thought that small changes in cochlear function which did not lead to changes in hearing threshold were detected by changes in DPOAEs. These findings suggest that parameters determined from the growth function, such as maximum DP level and DP threshold, are better indicators for monitoring cochlear function than is DPOAE amplitude for a single primary level, and demonstrate the usefulness of the growth function measurement for monitoring purposes. Furthermore, evaluation by changes in the overall growth function using combined parameters appeared to increase sensitivity in detection of subtle changes in cochlear function. In conclusion, DPOAE measurement can be a useful examination for clinical monitoring of cochlear function in Meniere's disease when the growth function is measured. [ABSTRACT FROM AUTHOR]

The differential display method was applied to identify genes, the expression of which is up-regulated in the cerebellar flocculus after unilateral labyrinthectomy (UL). Total RNA from sham-operated and labyrinthectomized rat flocculi was isolated, amplified by polymerase chain reaction (PCR) using a single arbitrary primer and separated by electrophoresis on a polyacrylamide gel. PCR products in amounts significantly higher in samples from labyrinthectomized animals than in those from controls were cut out of the gel and sequenced. One of the cDNA fragments showed 100% nucleotide sequence identity to the rat protein phosphatase 2A (PP2A)-β catalytic subunit mRNA. In situ hybridization histochemistry and Northern blot analysis showed that PP2A-β mRNA expression was intensely localized to the floccular Purkinje cell layer and up-regulated with a maximum increase within 2 days after UL. In labyrinthectomized rats, UL-induced nystagmus gradually disappeared within 3 days after UL. However, in animals with continuous floccular infusion of okadaic acid, a potent inhibitor of PP2A, UL-induced nystagmus lasted significantly longer. All these findings suggest that up-regulation of PP2A-β mRNA in floccular Purkinje cells after UL is involved in lesion-induced vestibular plasticity. So far, various kinds of neural plasticity-associated molecules have been investigated mainly by slice in vitro studies. This paper indicates that differential display is the feasible molecular biological in vivo method for an investigation about the mechanism of neural plasticity. [ABSTRACT FROM AUTHOR]

To determine the relationship between epidermal growth factor receptor (EGFR) and radiosensitivity, we immunostained cells from three maxillary carcinoma cell lines with an anti-EGFR antibody. The intensity of staining reactivity, determined by means of an image analysis system, was expressed as grey value (0-black to 255-white). The mean grey values for cell lines IMC-2, IMC-3, and IMC-4 were 181, 210, and 222, respectively, and differed significantly (p<0.001). This indicates that IMC-2 had the highest number of EGFR, followed by IMC-3 and IMC-4. The cells were then irradiated at 1, 2, 4, or 6 Gy, and cell survival was assessed by means of a standard colony-forming assay. IMC-2 had the highest survival rates at 1, 2 and 4 Gy, followed by IMC-3 and IMC-4. Therefore, the survival rates for IMC-2, IMC-3, and IMC-4 after irradiation increased in proportion to the amount of EGFR in each cell line. These results support the findings of previous clinical studies which showed that increased expression of EGFR was associated with higher recurrence rates of glottic and maxillary sinus carcinoma in patients treated with radiation therapy. The amount of EGFR in cells may therefore be associated with their radiosensitivity. [ABSTRACT FROM AUTHOR]