The recovery from AP adaptation in sensorineural hearing loss.

CONCLUSIONS: An abnormally slower action potential (AP) recovery from adaptation (decreased recovery, dR) was characteristically detected in many ears with sensorineural hearing loss (SNHL) but not Meniere's disease and idiopathic sudden SNHL. We assumed that this abnormal AP recovery from adaptation was attributed to an imbalance in the distributions of auditory neurons with high and low spontaneous firing rates. The significant difference of initial hearing level between dR and normal AP recovery groups (nR) was assumed to partially result from AP recovery being determined by the inner hair cell synapse, and not from outer hair cells. OBJECTIVE: This study aimed to detect the AP recovery pattern in SNHL. METHODS: Electrocochleography (ECochG) was performed transtympanically in 30 patients with SNHL. AP recovery was measured by a paired click stimulation paradigm as a function of inter-click intervals from 5 to 100 ms. RESULTS: The high prevalence of dR (9 of 30 ears) appears to be a characteristic ECochG finding in SNHL. Initial hearing level differed significantly between dR and nR groups.

Increased blood-brain barrier vulnerability to systemic inflammation in an Alzheimer disease mouse model.

Behavioral and psychological problems are often observed in patients with dementia such as that associated with Alzheimer disease, and these noncognitive symptoms place an extremely heavy burden on the family and caregivers. Although it is well know that these symptoms often are triggered by infection of peripheral organs, the underlying mechanisms for these pathological conditions are still unclear. In this study, using an Alzheimer amyloid precursor protein (APP)-transgenic mouse, we analyzed behavioral changes and brain inflammatory response induced by peripheral administration of lipopolysaccharide. Application of a unique in vivo microdialysis system revealed that the increase in brain inflammatory cytokine (interleukin-6) level was significantly higher in APP-Tg than in wild-type mice after peripheral lipopolysaccharide injection, which was associated with more severe sickness behaviors. The blood-brain barrier became more permeable in APP-Tg mice during peripherally evoked inflammation, suggesting the increased vulnerability of the blood-brain barrier to inflammation in this animal model of Alzheimer's disease. These findings might provide insight into the pathogenesis of noncognitive symptoms in dementia and a basis to develop new therapeutic treatments for them.

Electrocochleography in Meniere's disease: recovery from adaptation of the auditory action potential.

CONCLUSIONS: High prevalence rate of an enhanced summating potential (SP)/action potential (AP) ratio (≥0.35) is considered to result largely from the imbalances of Ca(2+) homeostasis in the endolymphatic space. An increase in Ca(2+) is thought to augment the SP. Furthermore, a greater inflow of Ca(2+) into inner hair cells is supposed to influence the disturbed release of neurotransmitter, which may induce pathological functioning of inner hair cell synapses. We speculate that such abnormal synaptic functioning is responsible for the development of abnormally increased AP recovery from adaptation (iR). OBJECTIVES: This study aimed to record the AP recovery from adaptation (AP recovery) and to investigate its clinical significance in association with other electrocochleography (ECochG) findings in Meniere's disease. METHODS: ECochG was performed transtympanically in 27 patients with Meniere's disease. AP recovery was measured by a paired-click stimulation paradigm as a function of interclick intervals from 5 to 100 ms. RESULTS: High prevalence of SP/AP ratio was observed in 27 patients. iR, suggesting abnormal functioning of inner hair cell synapse, was in many cases combined with an enhanced SP/AP ratio.

Electrocochleographic findings in recurrent idiopathic sudden sensorineural hearing loss.

CONCLUSION: The main differences in electrocochleography (ECochG) between recurrent and nonrecurrent idiopathic sudden sensorineural hearing loss (iSSNHL) were the high prevalence of an abnormally increased action potential (AP) recovery (iR) in nonrecurrent iSSNHL and the very low prevalence of iR in recurrent iSSNHL. An enhanced SP/AP ratio, low AP threshold, low initial hearing level, and up-sloping type of audiogram appear to be favorable prognostic factors in recurrent iSSNHL. OBJECTIVES: This study aimed to characterize differences in ECochG findings and other confounding prognostic factors between recurrent and nonrecurrent iSSNHL and to estimate how these findings are related to hearing outcome in recurrent iSSNHL. METHODS: ECochG was performed transtympanically in 23 and 42 ears with recurrent and nonrecurrent iSSNHL, respectively. AP recovery was measured using a paired-click stimulation paradigm. Differences in ECochG findings associated with confounding prognostic factors between recurrent and nonrecurrent iSSNHL, and between three outcome groups were assessed. RESULTS: iR was significantly more common in nonrecurrent iSSNHL (16 ears) than in recurrent iSSNHL (1 ear). In the outcome of recurrent iSSNHL, the prevalence rates of an enhanced summating potential (SP)/AP ratio, lower AP threshold, lower initial hearing level, and up-sloping type of audiogram were significantly higher in the cure group than in the improvement and no-recovery outcome groups.

Recovery from adaptation of the action potential in idiopathic sudden sensorineural hearing loss investigated using a paired-click stimulation paradigm.

CONCLUSION: We studied the compound action potential (AP) recovery from adaptation (AP recovery) in idiopathic sensorineural hearing loss (iSSNHL). Abnormal AP recovery was demonstrated in 15 of 45 patients, consisting of increased recovery (iR) over the normal range in 11 ears and decreased recovery (dR) under the normal range in 4 ears. The mechanisms for occurrence and clinical significance of these phenomena are currently unknown. OBJECTIVES: The purpose of this study was to investigate the pathologic features of AP recovery in iSSNHL. METHODS: Forty-five subjects with iSSNHL were enrolled and 18 normal-hearing subjects participated to assess the normal range of AP recovery. Equilevel paired clicks with inter-click interval from 5 to 100 ms were applied as acoustic stimuli. RESULTS: Eleven ears with iR and four ears with dR were found. The audiogram patterns of 11 iR and 4 dR ears exhibited 10 flat types, 3 high frequency loss types, and 2 low frequency loss types. Only 2 of 11 subjects with iR ears and 0 of 4 with dR ears complained of vertigo. No significant difference was observed in the comparison between AP threshold and hearing level of iR with those of normal recovery (nR) within the normal range.

A high recovery microsampling device based on a microdialysis probe for peptide sampling.

A high recovery microsampling probe based on microdialysis was devised. The new probe showed a high recovery (100%) of peptides in vitro at different perfusion flow rates (0.1-1.0 microl/min). At a high flow rate, 1.0 microl/min, a 10-fold increased in recovery of peptides compared to the conventional microdialysis probe was achieved. A probe made of a low molecular weight cutoff membrane is suitable for filtering off proteins. The new probe can be a useful tool for high recovery of peptides from living tissues.

Clinical significance of the summating potential-action potential ratio and the action potential latency difference for condensation and rarefaction clicks in Meniere's disease.

OBJECTIVES: This study was aimed to elucidate the diagnostic significance of the summating potential (SP)-action potential (AP) ratio and the AP latency difference between condensation and rarefaction clicks (AP con-rar difference) in Meniere's disease. METHODS: The AP and SP were recorded transtympanically in 67 patients with definite Meniere's disease. The SP/AP ratio and the AP con-rar difference were assessed in terms of 1) their interrelationship, 2) their relationship to hearing level, and 3) the rate of occurrence of abnormal values according to the stages of Meniere's disease. RESULTS: No correlation was found between the SP/AP ratio and the AP con-rar difference. Neither the SP/AP ratio in general nor the AP con-rar difference was correlated with the hearing level. However, enhanced values of the SP/AP ratio (0.35 or higher) were moderately correlated with the hearing level (r = 0.51), and their occurrence rate was 55.2%. An increased AP con-rar difference (0.13 ms or longer) was not correlated with the hearing level, and its occurrence rate was 50.2%; it appeared most frequently at stage 3 (p <0.05). CONCLUSIONS: An enhanced SP/AP ratio might not always indicate the presence of endolymphatic hydrops associated with an increase in endolymphatic pressure. An increased AP con-rar difference might reflect the presence of a biased basilar membrane resulting from an increased endolymphatic pressure, and hence it is diagnostically essential to simultaneously evaluate the SP/AP ratio and the AP con-rar difference.

Disposition of protein-bound 3-nitrotyrosine in rat plasma analysed by a novel protocol for HPLC-ECD.

3-Nitrotyrosine (NTyr) is considered as a biomarker of the generation of reactive nitrogen species (RNS). However, it is still difficult to determine its concentration in biological samples. To develop a reliable and high-throughput method, we optimized the conditions for high performance liquid chromatography and electrochemical detection (HPLC-ECD). The best separation of NTyr was achieved using a highly acidic mobile phase (pH 2.5). The concentration of protein-bound NTyr in plasma protein was 593.6 +/- 53.8 fmol/mg in rats treated with lipopolysaccharide (LPS) and 114.4 +/- 27.6 fmol/mg in control. After intravenous administration of in vitro-nitrated plasma protein, NTyr concentration decreased; the half-life was 63.4 +/- 16.8 h. Consistently, protein-bound NTyr concentration in plasma after LPS treatment declined gradually, but was detectable for 1 week. Our protocol is reproducible and suitable for analysing multiple clinical samples to study RNS production in vivo.

Recovery of human compound action potential using a paired-click stimulation paradigm.

The recovery process from adaptation of the compound action potential (CAP) was studied using an equilevel paired click stimulation paradigm in humans with normal hearing. The CAP amplitude to the second click of paired clicks was normalized to the amplitude to the first click. The second-click CAP amplitude recovered as a function of interclick interval (ICI) between the first and the second click of a pair. A regression line fitted to the recovered amplitude data demonstrated the logarithmic function of the ICI. Full recovery times changed from 118 to 278 ms with increasing click intensity. The regression lines for higher click intensities exhibited two different slopes in two ICI ranges: from 3 to 100 and 120 to 300 ms. We suppose that the CAP recovery for ICI <100 ms is attributable to both the relative refractoriness of auditory nerve and the short-term adaptation mechanisms, while, for ICI >100 ms chiefly to the short-term adaptation mechanisms. The recovery process of the second-click CAP slowed with increasing intensity, which is a similar result to that obtained in the animal experiments by Parham et al. The input-output (I-O) curve of the second-click CAP amplitudes exhibited a different slopes above and below 60 dB normal hearing level (nHL). We assume that the mechanisms underlying this characteristic curve pattern differ from those for the I-O curve of the CAP in response to single-click stimuli. We expect that investigating the CAP recovery in pathological ears will provide clinically useful information on cochlear synaptic function.

Abnormalities of the electrogastrogram in globus pharyngeus.

There appear to be multiple indicators for the presence of globus pharyngeus. We have assumed that patients with abnormal gastric motility can be included among those suffering from globus pharyngeus. Gastric motility can be examined non-invasively using the electrogastrogram (EGG). In this study, 32 patients (22 females, 10 males; mean age 55+/-13 years) with symptoms of globus pharyngeus consented to EGG recording. The EGGs of asymptomatic healthy adults (6 females, 10 males; mean age 28+/-5 years) were obtained as controls. No significant statistical difference was found in any of the measurement parameters between the two groups. However, we found that 9.4% of patients with globus pharyngeus exhibited abnormal gastric myoelectrical activity as measured by the EGG. This suggests that a small proportion of patients who complain of globus pharyngeus have abnormal gastric motility.

Quantitative assessment of protein-bound tyrosine nitration in airway secretions from patients with inflammatory airway disease.

Because reactive nitrogen species (RNS) have potent inflammatory activity, they may be involved in the inflammatory process in pulmonary diseases. We recently reported increased numbers of 3-nitrotyrosine immunopositive cells, which are evidences of RNS production, in the sputum of patients with chronic obstructive pulmonary disease (COPD) and patients with asthma compared with healthy subjects. In the present study, we attempted to quantify this protein nitration in the airways by means of high-performance liquid chromatography (HPLC) used together with an electrochemical detection system that we developed. Sputum samples were obtained from 15 stable COPD patients, 9 asthmatic patients and 7 healthy subjects by using hypertonic saline inhalation. The values for the molar ratio of protein-bound 3-nitrotyrosine/tyrosine in patients with asthma (4.31 +/- 1.13 x 10(-6), p < 0.05) and patients with COPD (3.04 +/- 0.36 x 10(-6), p < 0.01) were significantly higher than those in healthy subjects (1.37 +/- 0.19 x 10(-6)). The levels of protein-bound 3-nitrotyrosine in the airways were not significantly different in asthmatic patients and COPD patients. A significant negative correlation was found between values for protein-bound 3-nitrotyrosine/tyrosine and % FEV1 values in patients with COPD (r = -0.53, p < 0.05) but not in patients with asthma. These results suggest that our HPLC-electrochemical method is useful for quantifying RNS production in human airways. More importantly, they show that increased RNS production in the airways seems to contribute in a critical way to the pathogenesis of COPD, and that the effects of RNS in airways may differ in asthma and COPD.

Cortical potentials evoked by horizontal rotatory stimulation: the effects of angular acceleration.

OBJECTIVE: To examine the potentials evoked by rotatory stimulation, which we consider the optimal means of invoking angular acceleration and which may lead to clinical applications in patients with vertigo. MATERIAL AND METHODS: Horizontal rotatory stimulation using a trapezoidal waveform was performed with 3 different angular accelerations (20, 15 and 10 degrees/s2) used sequentially, with alternating clockwise and counterclockwise stimulation, to normal subjects and a patient with bilateral loss of vestibular function. RESULTS: It is likely that angular accelerations of < 20 degrees/s2 produce minor somatosensory effects. Clear potentials were evoked in 13/18 ears (72%) of the normal subjects with stimulation at an angular acceleration of 15 degrees/s2. No response was recorded in the patient with stimulation at 15 degrees/s2. CONCLUSION: We suggest that an angular acceleration of 15 degrees/s2 is optimal for clinical examinations.

Effects of nimodipine on quinine ototoxicity.

The compound action potential (CAP) in response to a click train stimulus was recorded at the round window of guinea pigs. Administration of quinine hydrochloride (200 mg/kg) significantly elevated the CAP thresholds by 5 to 25 dB (p < .05), and the CAP waveform elicited by the click train stimulus was abnormal. The amplitude of the CAP elicited by the second click was bigger than that elicited by the first click. These changes may be caused by an abnormally broadened N1 response to the first click in the click train. In contrast, CAP waveforms elicited by the second and subsequent clicks appeared normal. After administration of nimodipine (2 mg/kg), the CAP thresholds and waveforms elicited by the click train stimulus were unchanged. Simultaneous administration of both quinine (200 mg/kg) and nimodipine (2 mg/kg) resulted in the same electrophysiological changes as those induced by quinine alone. These results suggest that nimodipine prevents neither the deterioration in the CAP nor the abnormal properties in the response to a click train stimulus.

Simultaneous determination of glucose and L-lactate in rat brain by an electrochemical in vivo flow-injection system with an on-line microdialysis sampling.

An electrochemical in vivo flow-injection system with an on-line microdialysis sampling is proposed for the simultaneous monitoring of L-lactate and glucose in rat brain. In the first stage of the operation, the dialysate from the microdialysis probe is delivered to a sample loop of the six-way autoinjector by perfusing Ringer's solution for 80 s at 5 microl min(-1). In the second stage, the dialysate collected in the sample loop is automatically injected for 10 s into the flow-injection line. Injected dialysate is split into two streams and two portions pass through two channels with two different immobilized enzyme reactors (glucose oxidase and lactate oxidase immobilized reactors) to produce hydrogen peroxide from glucose and L-lactate in the dialysate. After a subsequent confluence of the streams, produced hydrogen peroxide can be detected amperometrically at a downstream poly(1,2-diaminobenzene) film-coated platinum electrode, without any interference from oxidizable species and proteins present in the dialysate. Because each channel has a different residence time, two peaks are obtained. The first peak corresponds to L-lactate and the second peak to glucose. The peak current is linearly related to the concentrations of L-lactate between 0.2 and 10 mM and glucose between 0.1 and 20 mM. The present method can be successfully applied to the simultaneous in vivo monitoring of L-lactate and glucose in rat brain. The analytical speed is 45 dialysates h(-1).

Changes in CAP adaptation in experimentally induced endolymphatic hydrops.

OBJECTIVE: To determine the effect of experimentally induced endolymphatic hydrops (ELHs) on compound action potential (CAP) adaptation. METHODS: The CAP was recorded 1 month after surgical treatment to produce ELH. The CAP threshold in response to click stimuli showed no significant differences between the hydropic and control groups. The CAP was elicited from the retroauricular-exposed round window using a silver ball electrode. Click trains consisting of 10 clicks with an interclick interval (Deltat) of either 4 or 8 ms were delivered through a loudspeaker placed in front of the animals' ears. The patterns of adaptation to these click trains were evaluated as functions of Deltat and intensity level. RESULTS: An abnormal pattern of CAP adaptation was observed in hydropic ears. CONCLUSIONS: These findings suggest that early ELH influences CAP adaptation.

Zinc deficiency and tinnitus.

OBJECTIVE: To determine if there is a correlation between serum zinc levels and audiometric performance in tinnitus patients. METHODS: Seventy-three patients participated in this study. Patient's age was restricted to 20-59 years. All patients were examined at the otolaryngology outpatient clinic of the St. Marianna University Toyoko Hospital. The control group consisted of 38 age- and sex-matched healthy volunteers. A blood sample was taken to measure serum zinc levels. Hypozincemia was set at a level of the mean minus one S.D. in the control group. An average hearing sensitivity was calculated as the mean value of hearing thresholds at five frequencies: 250, 500, 1000, 2000, and 4000 Hz. Normal hearing was indicated when the hearing threshold at each of these frequencies was within 20 dB of normal thresholds. RESULTS: There was no significant difference in serum zinc levels between patients with tinnitus and controls. However, patients with tinnitus who had normal hearing had significantly lower serum zinc levels compared to controls. In contrast, no significant difference in serum zinc levels was found between patients with tinnitus who had hearing loss, and controls. A significant correlation between average hearing sensitivity and serum zinc level was observed. CONCLUSIONS: These findings suggest that zinc is involved in the generation of tinnitus, especially in patients whose hearing is relatively normal.

Patency of inferior meatal antrostomy.

OBJECTIVE: To evaluate the patency and effectiveness of inferior meatal antrostomy for the treatment of maxillary lesions. METHODS: Patients suffering from moderate-to-severe chronic sinusitis who underwent inferior meatal antrostomies at St. Marianna University Toyoko Hospital and followed up for at least 1 year after surgery were selected. Thirty sides of 27 patients were analyzed. Postoperative mucociliary function was examined in seven sides of seven patients. RESULTS: No closure was observed in all 30 procedures. Out of 30 antra, 26 (86.7%) had normal antral mucosa. Recurrent mucosal lesions inside the maxillary sinus were successfully treated through the inferior meatal window. No cases showed circular flow on the india ink test. All sinuses exhibited a discharge from the middle meatal window and three out of seven sinuses exhibited a discharge from the inferior meatal window. CONCLUSIONS: Although long-term follow-up is required to determine the patency of inferior meatal antrostomy, initial results are encouraging. The inferior meatal window provides both intra- and postoperative benefits.

Neurotological findings in a patient with narrow internal auditory canal: a case report.

We report neurotological findings in a patient with unilateral narrow internal auditory canal, as confirmed by computed tomography. The patient presented no auditory brainstem response on the affected side. Vestibular tests including vestibular-evoked myogenic potentials (VEMP) and caloric test revealed normal function of both inferior and superior vestibular neural pathways.

A case of meningoencephalic herniation of the temporal bone.

A case of cerebrospinal fluid leakage from a meningoencephalic herniation of the temporal bone is presented. Computed tomography and magnetic resonance imaging were useful for a diagnosis of meningoencephalic herniation. After surgical treatment, no recurrence was observed during a 6-month follow-up period.