Secondary, profound, sensorineural hearing loss after recovery from haemolytic uraemic syndrome due to enterohaemorrhagic Escherichia coli, and subsequent cochlear implantation, in two Japanese children.

OBJECTIVES: To describe two cases of profound hearing loss secondary to enterohaemorrhagic Escherichia coli infection, and to report the efficacy of subsequent cochlear implantation. RESULTS: The first case was a four-year-old girl admitted to hospital with Escherichia coli O157 infection and haemolytic uraemic syndrome. Mild hearing loss was confirmed five months after discharge, progressing to profound loss three months later. At the age of seven years, she underwent cochlear implantation, with remarkable improvement in speech perception and production. The second case was a three-year-old boy admitted with haemolytic uraemic syndrome caused by Escherichia coli O111 infection. One year after disease onset, profound hearing loss was confirmed. Cochlear implantation at the age of five years produced significant recovery of auditory function. CONCLUSION: This study represents the first published report of secondary hearing loss after recovery from haemolytic uraemic syndrome caused by enterohaemorrhagic Escherichia coli. It indicates that cochlear implantation can restore hearing function in such patients.

A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy.

Auditory neuropathy is a hearing disorder characterized by normal outer hair cell function and abnormal neural conduction of the auditory pathway. Aetiology and clinical presentation of congenital or early-onset auditory neuropathy are heterogeneous, and their correlations are not well understood. Genetic backgrounds and associated phenotypes of congenital or early-onset auditory neuropathy were investigated by systematically screening a cohort of 23 patients from unrelated Japanese families. Of the 23 patients, 13 (56.5%) had biallelic mutations in OTOF, whereas little or no association was detected with GJB2 or PJVK, respectively. Nine different mutations of OTOF were detected, and seven of them were novel. p.R1939Q, which was previously reported in one family in the United States, was found in 13 of the 23 patients (56.5%), and a founder effect was determined for this mutation. p.R1939Q homozygotes and compound heterozygotes of p.R1939Q and truncating mutations or a putative splice site mutation presented with stable, and severe-to-profound hearing loss with a flat or gently sloping audiogram, whereas patients who had non-truncating mutations except for p.R1939Q presented with moderate hearing loss with a steeply sloping, gently sloping or flat audiogram, or temperature-sensitive auditory neuropathy. These results support the clinical significance of comprehensive mutation screening for auditory neuropathy.

Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells.

BACKGROUND: We isolated tumour endothelial cells (TECs), demonstrated their abnormalities, compared gene expression profiles of TECs and normal endothelial cells (NECs) by microarray analysis and identified several genes upregulated in TECs. We focused on the gene encoding biglycan, a small leucine-rich repeat proteoglycan. No report is available on biglycan expression or function in TECs. METHODS: The NEC and TEC were isolated. We investigated the biglycan expression and function in TECs. Western blotting analysis of biglycan was performed on sera from cancer patients. RESULTS: Biglycan expression levels were higher in TECs than in NECs. Biglycan knockdown inhibited cell migration and caused morphological changes in TECs. Furthermore, immunostaining revealed strong biglycan expression in vivo in human tumour vessels, as in mouse TECs. Biglycan was detected in the sera of cancer patients but was hardly detected in those of healthy volunteers. CONCLUSION: These findings suggested that biglycan is a novel TEC marker and a target for anti-angiogenic therapy.

Arachnoid cysts confined to the internal auditory canal or facial nerve canal.

OBJECTIVE: To illustrate the morphological characteristics and pathological significance of arachnoid cysts confined to the internal auditory canal or facial nerve canal. DESIGN: Retrospective case series. SUBJECTS: Three patients' cases were reviewed, and temporal bone sections examined histologically. RESULTS: In this series, three intracanalicular arachnoid cysts were found in the internal auditory canal and one in the facial nerve canal. All lesions consisted of distinct, space-occupying cysts with a sharp boundary with surrounding tissues. They were thin-walled and compressed the surrounding nerve trunks to a variable degree. However, there was no indication that patients suffered meatal nerve dysfunction. CONCLUSION: Arachnoid cysts can develop within the internal auditory canal or facial nerve canal. In our series, they were asymptomatic, which is quite different from most intracanalicular arachnoid cysts encountered in clinical practice.

Histopathological differences in bony destruction of malleus and incus following mastoidectomy.

OBJECTIVES: Upon direct inspection of surgically removed ossicles from the ears of patients with long-term post-mastoidectomy cavity problems, the extent of malleus destruction often appears greater in patients with a longer duration of cavity problems, whereas the extent of incus destruction does not appear to correlate with the duration of cavity problems. This study aimed to investigate this impression. MATERIALS AND METHODS: As a result of total middle-ear reconstruction, 41 ossicles (21 malleus and 20 incus bones) were obtained from 31 patients with post-mastoidectomy cavity problems. The ossicles were examined histopathologically, and the proportion of lamellar bone area to total bone area (expressed as percentage lamellar bone) was measured. We also calculated the inter-operation time, i.e. the time period between the previous mastoidectomy and the recent total middle-ear reconstruction; this parameter was used as an approximate measure of the duration of the patient's cavity problem. Correlations between percentage lamellar bone and inter-operation time were calculated for the two ossicles. RESULTS: The range of inter-operation times was seven to 65 years. We observed a correlation between percentage lamellar bone and inter-operation time for malleus bones (r = -0.512, p < 0.05), but not for incus bones. CONCLUSION: These results were in agreement with our pre-study impressions.

Comparison of Electroaudiometry with cochlear implant in children with inner ear anomaly.

The promontory stimulation test (PST) using a needle electrode has been used to evaluate the sense of the auditory nerve as a preoperative examination for cochlear implant in adults. Because this is a painful test, it is not suitable for children. It has been reported that children with inner ear anomaly showed poorer outcomes of hearing after cochlear implant. Electroaudiometry developed by Med-El Corporation, which is noninvasive, is a more suitable procedure for young children. Patients were three children less than five years old with inner ear anomaly. Two patients showed common cavity, and one showed narrow IAC with hypoplastic cochlear anomaly. By using Electroaudiometry, we analyzed electro-neural hearing of these children before cochlear implant, and compared their hearing after cochlear implant. Three children seemed to have residural electro-neural hearing because the dynamic range between stimulus level (SL) and uncomfortable level (UCL) was detected by using Electroaudiometry. After cochlear implant, their pure-tone audiograms showed moderate hearing thresholds, and their hearing detection and speech perception improved. These results suggest that Electroaudiometry is available for evaluating electro-neural hearing in young children with inner ear anomaly. It can provide useful information for a successful cochlear implant and evaluation of postoperative performances.

Unique technological voice method (The YUBA Method) shows clear improvement in patients with cochlear implants in singing.

It is known that children with cochlear implants tend to sing off-key, monotonously, and flat. There are a few reports that it is possible to improve off-key singing mainly through instruction using the falsetto voice for people with normal hearing. We examined whether their singing skills could be improved through instruction. Eight subjects (five boys and three girls aged 10.4+/-2.4 years) with cochlear implants were selected. Speech perception scores of short sentences were on average 66.5%+/-26.5%. We diagnosed their singing acuity by letting them sing a nursery song, well known to all of them, before and after the instruction. The mean fundamental frequencies of their singing approached the mean Musical Instrument Digital Interface (MIDI)-specified frequencies as references and the deviation between fundamental frequencies of their singing and reference MIDI sounds became smaller. This study shows a clear improvement in the singing ability of children with cochlear implants through a unique technological voice method, mainly focused on the falsetto voice in this experiment.

Advancement in singing ability using The YUBA Method in patients with cochlear implants.

CONCLUSION: Although overall improvement was not so dramatic due to a lack of retention, session by session advancement of matching pitch for targeted MIDI (Musical Instrument Digital Interface) sound was predominantly obvious. It was proved that The YUBA Method worked to improve singing ability for patients with cochlear implants. OBJECTIVES: This study sought to verify whether or not the Yuba theory and method improved the singing ability of patients with cochlear implants. SUBJECTS AND METHODS: Based on diagnosis, the instructor experimented to improve matching pitch of singing for three patients with cochlear implants using The YUBA Method. The mean fundamental frequencies and standard deviation of singing were then compared with before and after instructions to patients. The instruction was given for over 40 days at the University of Tokyo Hospital. RESULTS: For each patient, the mean fundamental frequencies of their singing approached the mean MIDI specified frequencies as references for tests done in all three songs. Overall, the SD between fundamental frequencies of their singing and reference MIDI sounds became smaller.

Multiple neural origins of early auditory evoked potential of rat.

The multiple-origin hypothesis has been often considered for an unclear neurogenesis of a characteristic wave in various evoked potentials, none of which has been verified so far. Auditory evoked potential (AEP) in the temporal cortex of rodents has typical slow positive/negative (P1/N1) biphasic waves, which are occasionally associated with an additional 2-4-ms earlier small deflection (P0/N0). Despite previous extensive efforts, P0/N0 deflection is still discussed within the multiple-origin hypothesis. In this historical perspective, we hypothesized that observable AEP is an additive mixture of mutually temporally independent signals from different origins, and that the balance of the mixture impacts on the waveform of AEP. We attempted to verify this hypothesis for the first time by independent component analysis (ICA) of epidurally densely mapped AEPs in the primary auditory cortex of rats. The mapping showed that low amplitude AEPs tended to have more P0/N0 deflections in both pentobarbital- and ketamine/xylazine-anesthesia preparations. ICA of these AEP maps suggested that AEP consisted of at least three independent components and that the deflection appeared when subcortical contribution to AEP was equal to or larger than cortical contribution. In epicranially measured evoked potentials, subcortical and cortical contributions are mixed together because distances from electrodes to cortical sources approximate distances to subcortical sources. In such conditions, e.g. in human scalp-recording experiments or routine clinical screenings, our idea is specifically worth considering for the interpretation of signals.

The effect of methotrexate (MTX) on expression of signalling lymphocytic activation molecule (SLAM) in patients with rheumatoid arthritis (RA) and its role in the regulation of cytokine production.

OBJECTIVE: To investigate the effect of methotrexate (MTX) on cytokine production by activated CD4+ T-cells in patients with rheumatoid arthritis (RA). METHODS: The effect of MTX on intracellular expression of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), and cell surface expression of signalling lymphocytic activation molecule (SLAM) from freshly isolated peripheral blood mononuclear cells (PBMCs), and after in vitro culture with or without MTX, was analysed with flow cytometry in 18 patients with RA and 20 healthy controls. RESULTS: Intracellular expression of IFN-gamma and IL-4 on freshly isolated CD4+ T-cells was significantly higher in patients with RA than in the controls (p<0.05). Intracellular expression of both IFN-gamma and IL-4 after culture with MTX was significantly lower than those after culture without MTX in patients with RA. Although no significant difference was observed in SLAM expression on freshly isolated CD4+ T-cells between patients with RA and the controls, MTX significantly decreased SLAM expression on both activated IFN-gamma+ and IL-4+CD4+ T-cells in patients with RA. CONCLUSION: In vitro modulation of the cytokine network by MTX, IFN-gamma, and IL-4 is one of the major targets for MTX, and production of IFN-gamma and IL-4 by PBMCs may be suppressed by SLAM on activated CD4+ T-cell in patients with RA.

Myelin-deficiency in the cochlear nerve of the 'bt' mutant hamster.

In a previous report, we showed abnormal auditory evoked potentials in the mutant hamster, 'black tremor (bt)', with significantly prolonged wave latencies of auditory brainstem responses and prolonged N1 latencies of compound action potentials, but normal cochlear microphonics. In this report, we present the results of morphological studies supporting the results of our electrophysiological studies of the auditory pathway in bt. Observation by transmission electron microscopy revealed an abnormal myelin sheath surrounding the spiral ganglion cells, and a thinner compact myelin sheath surrounding the axons in bt than in normal hamsters. The bt hamster has a myelin deficiency not only in the brainstem, but also in the cochlear nerve.

Time-intensity trade of bilaterally bone-conducted sounds in normal hearing subjects.

OBJECTIVE AND METHODS: In an effort to examine the rules by which information of bilaterally applied bone-conducted signals arising from interaural time differences (ITD) and interaural intensity differences (IID) is combined, data were measured for continuous 500 Hz narrow-band noise at 60 dBHL in 30 normal-hearing subjects using a centering method. Time-intensity trading functions were obtained by means of a sound image shifted towards one side by presenting an ITD, and shifted back to a centered sound image by varying the IID in the same ear. ITD values were varied from -600 to +600 microseconds at 200 microseconds steps, where negative values indicate delays to the right ear. RESULTS: Time-intensity trading functions in response to bone-conducted signals showed significantly lower discrimination thresholds across IIDs, when compared to a control group with applied air-conducted signals. These findings can be interpreted as a constructive interference effect related to the intimate mechanism of bilateral bone conduction, where interaural time differences play a major role. CONCLUSION: Time-intensity trade of bilaterally bone-conducted sounds in normal-hearing subjects is the highly sensitive. The high speed of sound through the skull may be the main reason for the high sensitivity of time-intensity trading.

Transfection of young guinea pig vestibular cells in vitro with an adenovirus vector.

This study shows distributions of lacZ-positive cells in the vestibular labyrinthine explants of young guinea pigs with mature ears. When adenovirus lacZ vectors were administered to the vestibular labyrinth following removal of the otoconial membrane, lacZ-positive cells were observed in the mesothelial cells in the perilymphatic space, in the sensory and supporting cells in the utricle and ampulla, and in the transitional and dark cells in the ampulla. When the otoconial membrane was preserved, lacZ-positive cells were not distributed in the utricular sensory epithelium. These findings suggest that adenovirus vectors can transform a variety of vestibular epithelial cells, but that it is difficult for adenovirus vectors to pass through the otoconial membrane.

Frequency sensitivity range of the saccule to bone-conducted stimuli measured by vestibular evoked myogenic potentials.

Vestibular evoked myogenic potentials (VEMPs) occurring in cervical muscles after intense sound stimulation conducted by air or bone are thought to be a polysynaptic response of otolith-vestibular nerve origin. We report the results of an experiment to investigate whether acoustic stimulation of the saccule by bone conduction produces VEMPs in which response amplitudes are somewhat sensitive to stimulus frequency, as appears to be the case with air-conducted stimuli. Prior to this we investigated the effect of stimulation repetition rate on bone-conducted VEMPs (B-VEMPs) at stimulus frequencies of 200 and 400 Hz with five different repetition rates (5, 10, 20, 40, and 80 Hz). B-VEMPs were recorded from 12 normal hearing subjects in response to bone-conducted 70 dB (normal hearing level), 10-ms tone bursts (rise/fall time=1 ms and plateau time=8 ms) at frequencies of 100, 200, 400, 800, 1600 and 3200 Hz. Our study showed that B-VEMP amplitudes were highest at 10 Hz but decreased as the repetition rate increased. B-VEMP response amplitudes were found to be maximal for stimulus frequencies from 200 to 400 Hz. This response may contribute to the perception of loud sounds.

Analysis of optokinetic nystagmus in patients with lesions on the left unilateral parietal lobe or the entire left hemisphere.

Optokinetic nystagmus (OKN) was studied by computer analysis in nine patients with lesions on the left unilateral parietal lobe (group A) and in five patients with lesions on the entire left hemisphere (group B), as confirmed by CAT or MRI scans. OKN stimulation and recordings were evaluated based on the optokinetic pattern (OKP). In group A, there was no directional preponderance. However, in group B, the Electronystagmography recordings showed typical asymmetry of OKP. This asymmetry was revealed by a low amplitude and a significantly impaired slow-phase eye velocity of the right OKP. Asymmetry of OKP resulted from the impaired slow-phase eye velocity of the contralateral OKN to the damaged hemisphere because of a slight change in fast-phase eye velocity.

[Current condition of early peripheral lung cancer and related problems].

Early peripheral lung cancer is defined as a tumor whose diameter is within 20 mm and that has not metastasized to lymph nodes. We developed thoracoscopic surgery (two windows method) in 1993. We have been conducting this thoracoscopic surgery in early peripheral lung cancers to identify possible indications as well as to clarify problems related to early peripheral lung cancer. The subjects of this study were 176 tumors, with diameters within 30 mm, including 97 lung cancers with diameters within 20 mm. Of the 97 tumors 20 mm or less in diameter, 18 were N 1 or more severe (N 1, 8 cases: N 2, 10 cases). One patient (N 2) died of bone metastasis and two patients died due to diseases other than lung cancer. Nearly 20% of the patients with tumors 20 mm or less were in the advanced stage, suggesting that mediastinal lymph node resection is necessary. Based on these results, it is advisable to define tumors with a diameter of no more than 10 mm as early peripheral lung cancer.

Retrospective and prospective coding for predicted reward in the sensory thalamus.

Reward is important for shaping goal-directed behaviour. After stimulus-reward associative learning, an organism can assess the motivational value of the incoming stimuli on the basis of past experience (retrospective processing), and predict forthcoming rewarding events (prospective processing). The traditional role of the sensory thalamus is to relay current sensory information to cortex. Here we find that non-primary thalamic neurons respond to reward-related events in two ways. The early, phasic responses occurred shortly after the onset of the stimuli and depended on the sensory modality. Their magnitudes resisted extinction and correlated with the learning experience. The late responses gradually increased during the cue and delay periods, and peaked just before delivery of the reward. These responses were independent of sensory modality and were modulated by the value and timing of the reward. These observations provide new evidence that single thalamic neurons can code for the acquired significance of sensory stimuli in the early responses (retrospective coding) and predict upcoming reward value in the late responses (prospective coding).

An isolated and sporadic auditory neuropathy (auditory nerve disease): report of five patients.

Five patients of various ages with difficulty in speech discrimination were evaluated. All showed evidence of abnormal auditory brainstem responses (ABRs) beginning with the VIIIth cranial nerve. Broad summating potentials were evoked on their electrocochleograms (EcochGs) and they all exhibited almost normal cochlear outer hair cell function by otoacoustic emissions (OAEs) recordings. Behavioural audiometric testing revealed a mild to moderate elevation of pure-tone threshold in all patients. The shape of their pure-tone losses varied, being predominantly low-frequency in four patients (rising slope pattern) and flat across all frequencies in one patient. Speech intelligibility scores of all patients were poor and out of proportion to what would have been expected if threshold elevation of pure-tone was of cochlear origin (i.e. markedly poor scores on the speech audiogram with good scores on the auditory comprehension test). Patients were neurologically normal when the hearing impairment was first manifested. We suggest that this type of hearing impairment is due to an isolated and sporadic disorder of auditory nerve function. It occurs in isolation and does not seem to be part of a generalized neuropathological process.

Binaural interaction of bone-conducted auditory brainstem responses.

Bone-conducted auditory brainstem responses (ABRs) elicited by monoaural stimulation are very useful for evaluating hearing in children with congenital atresia of both ears. In a previous study of sound lateralization in children with congenital atresia of both ears, using bilateral bone-conducted stimuli, we found that most of the children could sufficiently retain binaural hearing ability in terms of both intensity and time differences. In this study we attempted to record bilateral bone-conducted ABRs in normal subjects in order to explore binaural interaction objectively. The study revealed that binaural interaction exists in bone-conducted ABRs. This can be taken as neurophysiological evidence that sound lateralization can be detected by children with bilateral microtia and atresia.