The Experts below are selected from a list of 16158 Experts worldwide ranked by ideXlab platform
Kenneth E Hancock - One of the best experts on this subject based on the ideXlab platform.
-
middle ear Muscle Reflex and word recognition in normal hearing adults evidence for cochlear synaptopathy
Ear and Hearing, 2020Co-Authors: Anita M Mepani, Kenneth E Hancock, Stephane F Maison, Sarah A Kirk, Kara Bennett, Victor De GruttolaAbstract:Objectives Permanent threshold elevation after noise exposure, ototoxic drugs, or aging is caused by loss of sensory cells; however, animal studies show that hair cell loss is often preceded by degeneration of synapses between sensory cells and auditory nerve fibers. The silencing of these neurons, especially those with high thresholds and low spontaneous rates, degrades auditory processing and may contribute to difficulties in understanding speech in noise. Although cochlear synaptopathy can be diagnosed in animals by measuring suprathreshold auditory brainstem responses, its diagnosis in humans remains a challenge. In mice, cochlear synaptopathy is also correlated with measures of middle ear Muscle (MEM) Reflex strength, possibly because the missing high-threshold neurons are important drivers of this Reflex. The authors hypothesized that measures of the MEM Reflex might be better than other assays of peripheral function in predicting difficulties hearing in difficult listening environments in human subjects. Design The authors recruited 165 normal-hearing healthy subjects, between 18 and 63 years of age, with no history of ear or hearing problems, no history of neurologic disorders, and unremarkable otoscopic examinations. Word recognition in quiet and in difficult listening situations was measured in four ways: using isolated words from the Northwestern University auditory test number six corpus with either (a) 0 dB signal to noise, (b) 45% time compression with reverberation, or (c) 65% time compression with reverberation, and (d) with a modified version of the QuickSIN. Audiometric thresholds were assessed at standard and extended high frequencies. Outer hair cell function was assessed by distortion product otoacoustic emissions (DPOAEs). Middle ear function and Reflexes were assessed using three methods: the acoustic Reflex threshold as measured clinically, wideband tympanometry as measured clinically, and a custom wideband method that uses a pair of click probes flanking an ipsilateral noise elicitor. Other aspects of peripheral auditory function were assessed by measuring click-evoked gross potentials, that is, summating potential (SP) and action potential (AP) from ear canal electrodes. Results After adjusting for age and sex, word recognition scores were uncorrelated with audiometric or DPOAE thresholds, at either standard or extended high frequencies. MEM Reflex thresholds were significantly correlated with scores on isolated word recognition, but not with the modified version of the QuickSIN. The highest pairwise correlations were seen using the custom assay. AP measures were correlated with some of the word scores, but not as highly as seen for the MEM custom assay, and only if amplitude was measured from SP peak to AP peak, rather than baseline to AP peak. The highest pairwise correlations with word scores, on all four tests, were seen with the SP/AP ratio, followed closely by SP itself. When all predictor variables were combined in a stepwise multivariate regression, SP/AP dominated models for all four word score outcomes. MEM measures only enhanced the adjusted r values for the 45% time compression test. The only other predictors that enhanced model performance (and only for two outcome measures) were measures of interaural threshold asymmetry. Conclusions Results suggest that, among normal-hearing subjects, there is a significant peripheral contribution to diminished hearing performance in difficult listening environments that is not captured by either threshold audiometry or DPOAEs. The significant univariate correlations between word scores and either SP/AP, SP, MEM Reflex thresholds, or AP amplitudes (in that order) are consistent with a type of primary neural degeneration. However, interpretation is clouded by uncertainty as to the mix of pre- and postsynaptic contributions to the click-evoked SP. None of the assays presented here has the sensitivity to diagnose neural degeneration on a case-by-case basis; however, these tests may be useful in longitudinal studies to track accumulation of neural degeneration in individual subjects.
-
the middle ear Muscle Reflex in the diagnosis of cochlear neuropathy
Hearing Research, 2016Co-Authors: Michelle D Valero, Kenneth E HancockAbstract:Cochlear neuropathy, i.e. the loss of auditory nerve fibers (ANFs) without loss of hair cells, may cause hearing deficits without affecting threshold sensitivity, particularly if the subset of ANFs with high thresholds and low spontaneous rates (SRs) is preferentially lost, as appears to be the case in both aging and noise-damaged cochleas. Because low-SR fibers may also be important drivers of the medial olivocochlear Reflex (MOCR) and middle-ear Muscle Reflex (MEMR), these Reflexes might be sensitive metrics of cochlear neuropathy. To test this hypothesis, we measured Reflex strength and Reflex threshold in mice with noise-induced neuropathy, as documented by confocal analysis of immunostained cochlear whole-mounts. To assay the MOCR, we measured contra-noise modulation of ipsilateral distortion-product otoacoustic emissions (DPOAEs) before and after the administration of curare to block the MEMR or curare + strychnine to also block the MOCR. The modulation of DPOAEs was 1) dominated by the MEMR in anesthetized mice, with a smaller contribution from the MOCR, and 2) significantly attenuated in neuropathic mice, but only when the MEMR was intact. We then measured MEMR growth functions by monitoring contra-noise induced changes in the wideband reflectance of chirps presented to the ipsilateral ear. We found 1) that the changes in wideband reflectance were mediated by the MEMR alone, and 2) that MEMR threshold was elevated and its maximum amplitude was attenuated in neuropathic mice. These data suggest that the MEMR may be valuable in the early detection of cochlear neuropathy.
Yu Wen Chen - One of the best experts on this subject based on the ideXlab platform.
-
serotonin enhances oxybuprocaine and proxymetacaine induced cutaneous analgesia in rats
European Journal of Pharmacology, 2019Co-Authors: Ankuo Chou, Jhijoung Wang, Yu Wen Chen, Chong Chi Chiu, Ching Hsia HungAbstract:The aim of the study was to investigate the analgesic effects of adding serotonin to oxybuprocaine or proxymetacaine preparations. We employed a rat model of the cutaneous trunci Muscle Reflex (CTMR) to conduct the dose-response curves and duration of drugs (oxybuprocaine, proxymetacaine, or serotonin) as an infiltrative anesthetic. The use of isobolographic methods to analyze the drug-drug interactions. We showed that oxybuprocaine and proxymetacaine, as well as serotonin produced dose-dependent skin antinociception. On the basis of 50% effective dose (ED50), the rank order of drug potency was serotonin [7.22 (6.45-8.09) μmol/kg] < oxybuprocaine [1.03 (0.93-1.15) μmol/kg] < proxymetacaine [0.59 (0.53-0.66) μmol/kg] (P < 0.01 for each comparison). The sensory block duration of serotonin was longer (P < 0.01) than that of oxybuprocaine or proxymetacaine at the equipotent doses (ED25, ED50, and ED75). The mixture of serotonin with oxybuprocaine or proxymetacaine produced a better analgesic effect than the drug itself. We have concluded that oxybuprocaine, proxymetacaine, or serotonin displays dose-related cutaneous analgesia. Oxybuprocaine or proxymetacaine is more potent and has a shorter duration of cutaneous analgesia than serotonin. Serotonin produces a synergistic antinociceptive interaction with oxybuprocaine or proxymetacaine.
-
mexiletine co injected with clonidine increases the quality and duration of cutaneous analgesia in response to skin pinpricks in the rat
Neuroscience Letters, 2017Co-Authors: Ming Ming Han, Jhijoung Wang, Yu Wen Chen, Chong Chi Chiu, Ching Hsia HungAbstract:Abstract The goal of the experimental design was to assess the cutaneous analgesic effect of mexiletine by co-injection with clonidine. The effect of nociceptive block was evaluated according to the inhibition of the cutaneous trunci Muscle Reflex (CTMR) in response to skin pinpricks in rats. The dose-related analgesic effect of mexiletine alone or mexiletine co-administrated with clonidine was constructed after subcutaneous injection. Subcutaneous injections of mexiletine elicited dose-related cutaneous analgesia. Compared with mexiletine (1.8 μmol), adding clonidine to mexiletine (1.8 μmol) solutions for skin nociceptive block potentiated and prolonged the action ( p 0.01). Mexiletine (6 μmol) combined with clonidine extended the duration of cutaneous analgesia when compared with mexiletine (6 μmol) alone ( p 0.01). Co-administration of clonidine increases the potency and extends the duration of cutaneous analgesia by mexiletine, and the minimal dose of clonidine to intensify the analgesic effect is 0.06 μmol.
-
The Addition of Epinephrine to Proxymetacaine or Oxybuprocaine Solution Increases the Depth and Duration of Cutaneous Analgesia in Rats
Regional anesthesia and pain medicine, 2016Co-Authors: Yu Wen Chen, Jhijoung Wang, Chung-dann Kan, Ching Hsia HungAbstract:Background The aim of this experiment was to investigate the interaction between epinephrine and 2 local anesthetics (proxymetacaine or oxybuprocaine) using subcutaneous injections under the hairy skin, thereby simulating infiltration blocks. Methods Using a rat model of cutaneous trunci Muscle Reflex in response to local skin pinpricks, the anesthetic properties of proxymetacaine and oxybuprocaine alone and in combination with epinephrine as an infiltrative anesthetic were tested. Isobolographic analysis was used for the analgesic interactions between adjuvant epinephrine and the local anesthetics. Lidocaine was used as a control group. Results Oxybuprocaine, proxymetacaine, and lidocaine elicited a dose-dependent block to pinpricks. On the 50% effective dose (ED50) basis, their relative potencies were proxymetacaine [0.126 (0.113–0.141) μmol] greater than oxybuprocaine [0.208 (0.192–0.226) μmol] greater than lidocaine [6.331 (5.662–7.079) μmol] (P Conclusions We concluded that proxymetacaine and oxybuprocaine were more potent and produced greater duration of nociceptive block than lidocaine. The use of epinephrine augmented the potency and prolonged the duration of proxymetacaine, oxybuprocaine, and lidocaine as an infiltrative anesthetic.
-
dextrorphan for prolonged skin infiltration anesthesia by adding epinephrine in rats
International Journal of Anesthesiology Research., 2014Co-Authors: Kuanting Chen, Jhijoung Wang, Yu Wen ChenAbstract:Dextrorphan could be a local anesthetic, while adding epinephrine to the local anesthetics prolonged their duration of action. Here we investigated whether epinephrine as adjuvant could prolong the local anesthetic effect of dextrorphan. The cutaneous analgesic effect of the addition of epinephrine (5 μg/mL) to dextrorphan was assessed in rats following the blockade of cutaneous trunci Muscle Reflex through subcutaneous injection of drugs. We showed that subcutaneous dextrorphan elicited dose-dependent cutaneous analgesia. Co-administration of epinephrine (5
-
dextrorphan for prolonged skin infiltration anesthesia by adding epinephrine in rats
International Journal of Anesthesiology Research., 2014Co-Authors: Kuanting Chen, Jhijoung Wang, Yu Wen ChenAbstract:Dextrorphan could be a local anesthetic, while adding epinephrine to the local anesthetics prolonged their duration of action. Here we investigated whether epinephrine as adjuvant could prolong the local anesthetic effect of dextrorphan. The cutaneous analgesic effect of the addition of epinephrine (5 μg/mL) to dextrorphan was assessed in rats following the blockade of cutaneous trunci Muscle Reflex through subcutaneous injection of drugs. We showed that subcutaneous dextrorphan elicited dose-dependent cutaneous analgesia. Co-administration of epinephrine (5 g/mL) with dextrorphan at 50% effective dose (ED50) or ED95 had a longer duration than dextrorphan (ED50 or ED95) alone, respectively. This study indicated for the first time that the mixtures of epinephrine with dextrorphan increased the duration as an infiltrative anesthetic.
Scott A Smith - One of the best experts on this subject based on the ideXlab platform.
-
skeletal Muscle Reflex induced sympathetic dysregulation and sensitization of Muscle afferents in type 1 diabetic rats
Hypertension, 2020Co-Authors: Rie Ishizawa, Jere H Mitchell, Scott A Smith, Norio Hotta, Gary A Iwamoto, Wanpen Vongpatanasin, Masaki MizunoAbstract:The blood pressure response to exercise is exaggerated in the type 1 diabetes mellitus (T1DM). An overactive exercise pressor Reflex (EPR) contributes to the potentiated pressor response. However, ...
-
spironolactone or eplerenone treatment reduce the exaggerated pressor response to Muscle Reflex activation in spontaneously hypertensive rats
The FASEB Journal, 2015Co-Authors: Ryan M Downey, Masaki Mizuno, Jere H Mitchell, Wanpen Vongpatanasin, Philip M Brown, Scott A SmithAbstract:Exercise is a beneficial treatment for hypertension. However, hypertensive patients frequently exhibit a dangerous, exaggerated rise in mean arterial pressure (MAP) during physical activity. Evidence suggests that the skeletal Muscle exercise pressor Reflex (EPR) plays a primary role in evoking this potentiated responsiveness, although the mechanisms remain largely undetermined. Studies suggest that mineralcorticoid receptors (MR) can contribute significantly to hypertension. Whether MR activation mediates EPR overactivity is unknown. Changes in MAP in response to EPR activation (via electrically-induced hindlimb Muscle contraction) were assessed in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Additional SHR were fed (3 weeks) either normal chow (NC) or a customized diet containing the mineralcorticoid receptor antagonists spironolactone (SPIR, 50 mg/kg/day) or eplerenone (EPL, 100 mg/kg/day). The MAP response to EPR activation was markedly larger in SHR (37±8 mmHg) compared ...
-
skeletal Muscle Reflex mediated changes in sympathetic nerve activity are abnormal in spontaneously hypertensive rats
American Journal of Physiology-heart and Circulatory Physiology, 2011Co-Authors: Masaki Mizuno, Megan N Murphy, Jere H Mitchell, Scott A SmithAbstract:In hypertension, the blood pressure response to exercise is exaggerated. We demonstrated previously that this heightened pressor response to physical activity is mediated by an overactive skeletal ...
Rüdiger Köhling - One of the best experts on this subject based on the ideXlab platform.
-
Repetitive Peripheral Magnetic Nerve Stimulation (rPMS) as Adjuvant Therapy Reduces Skeletal Muscle Reflex Activity.
Frontiers in neurology, 2019Co-Authors: Volker Zschorlich, Martin Hillebrecht, Tammam Tanjour, Frank Behrendt, Timo Kirschstein, Rüdiger KöhlingAbstract:Background: The reduction of Muscle hypertonia and spasticity, as well as an increase in mobility, is an essential prerequisite for the amelioration of physiotherapeutical treatments. Repetitive peripheral magnetic nerve stimulation (rPMS) is a putative adjuvant therapy that improves the mobility of patients. Methods: Thirty-eight participants underwent either an rPMS treatment (N=19) with a 5 Hz stimulation protocol at the soleus Muscle or with sham stimulation (N=19). The stimulation took place over 5 minutes. The study was conducted in a pre-test post-test design with matched groups. Results: The primary outcome was a significant reduction of the Reflex activity of the soleus Muscle, triggered by a computer-aided tendon-Reflex impact. Outcome measures were taken at the baseline and after the following intervention. The pre-post differences of the tendon Reflex response activity were -23.7% (P < 0.001) for the treatment group. No significant effects showed in the sham stimulation group. Conclusion: Low-frequency magnetic stimulation (5 Hz rPMS) exhibits a substantial reduction of the tendon Reflex amplitude. The 5 Hz rPMS treatment seems to be an effective procedure to reduce muscular stiffness, increase mobility, and thus, makes the therapeutic effect of neuro-rehabilitation more effective. For this reason, the 5 Hz rPMS treatment might have the potential to be used as an adjuvant therapy in the rehabilitation of gait and posture control in patients suffering from limited mobility due to spasticity.
Douglas H. Keefe - One of the best experts on this subject based on the ideXlab platform.
-
aural acoustic stapedius Muscle Reflex threshold procedures to test human infants and adults
Jaro-journal of The Association for Research in Otolaryngology, 2017Co-Authors: Douglas H. Keefe, Patrick M Feeney, Lisa L Hunter, Denis F FitzpatrickAbstract:Power-based procedures are described to measure acoustic stapedius-Muscle Reflex threshold and supra-threshold responses in human adult and infant ears at frequencies from 0.2 to 8 kHz. The stimulus set included five clicks in which four pulsed activators were placed between each pair of clicks, with each stimulus set separated from the next by 0.79 s to allow for Reflex decay. Each click response was used to detect the presence of Reflex effects across frequency that were elicited by a pulsed broadband-noise or tonal activator in the ipsilateral or contralateral test ear. Acoustic Reflex shifts were quantified in terms of the difference in absorbed sound power between the initial baseline click and the later four clicks in each set. Acoustic Reflex shifts were measured over a 40-dB range of pulsed activators, and the acoustic Reflex threshold was objectively calculated using a maximum 10 likelihood procedure. To illustrate the principles underlying these new Reflex tests, Reflex shifts in absorbed sound power and absorbance are presented for data acquired in an adult ear with normal hearing and in two infant ears in the initial and follow-up newborn hearing screening exams, one with normal hearing and the other with a conductive hearing loss. The use of absorbed sound power was helpful in classifying an acoustic Reflex shift as present or absent. The resulting Reflex tests are in use in a large study of wideband clinical diagnosis and monitoring of middle-ear and cochlear function in infant and adult ears.
-
wideband ipsilateral measurements of middle ear Muscle Reflex thresholds in children and adults
Journal of the Acoustical Society of America, 2007Co-Authors: Kim S Schairer, John C Ellison, Denis F Fitzpatrick, Douglas H. KeefeAbstract:The goals of the current study were to: 1) evaluate the feasibility of a new wideband approach to measuring middle-ear Muscle Reflex (MEMR) status, and 2) to test the hypothesis that ipsilateral thresholds elicited with 1 or 2kHz tones and broadband noise activators on a wideband acoustic transfer function (WATF) system are lower than thresholds elicited on a clinical system. Clinical MEMR tests have limitations, including the need for high activator levels to elicit a shift in a narrowband probe (e.g., a 0.226 or 1kHz tone). Wideband MEMR tests using WATFs may elicit the Reflex at lower levels because a wideband probe (click) is used and the threshold detection criterion can be wideband. Mean wideband MEMR thresholds across 40 normal-hearing adult ears were 2.2–4.0dB lower than clinical MEMR thresholds, depending on the activator and specific WATF test used (admittance magnitude or energy reflectance). Wideband MEMR has potential clinical utility beyond the adult population, including use in newborn and preschool hearing screenings. In a newborn hearing screening, for example, wideband MEMR could be completed with the same system as otoacoustic emissions. However, further investigations in infants and young children are needed.
-
Simultaneous Measurement of Noise-Activated Middle-Ear Muscle Reflex and Stimulus Frequency Otoacoustic Emissions
Journal of the Association for Research in Otolaryngology, 2006Co-Authors: Shawn S. Goodman, Douglas H. KeefeAbstract:Otoacoustic emissions serve as a noninvasive probe of the medial olivocochlear (MOC) Reflex. Stimulus frequency otoacoustic emissions (SFOAEs) elicited by a low-level probe tone may be the optimal type of emission for studying MOC effects because at low levels, the probe itself does not elicit the MOC Reflex [Guinan et al. (2003) J. Assoc. Res. Otolaryngol. 4:521]. Based on anatomical considerations, the MOC Reflex activated by ipsilateral acoustic stimulation (mediated by the crossed olivocochlear bundle) is predicted to be stronger than the Reflex to contralateral stimulation. Broadband noise is an effective activator of the MOC Reflex; however, it is also an effective activator of the middle-ear Muscle (MEM) Reflex, which can make results difficult to interpret. The MEM Reflex may be activated at lower levels than measured clinically, and most previous human studies have not explicitly included measurements to rule out MEM Reflex contamination. The current study addressed these issues using a higher-frequency SFOAE probe tone to test for cochlear changes mediated by the MOC Reflex, while simultaneously monitoring the MEM Reflex using a low-frequency probe tone. Broadband notched noise was presented ipsilaterally at various levels to elicit probe-tone shifts. Measurements are reported for 15 normal-hearing subjects. With the higher-frequency probe near 1.5 kHz, only 20% of subjects showed shifts consistent with an MOC Reflex in the absence of an MEM-induced shift. With the higher-frequency probe near 3.5 kHz, up to 40% of subjects showed shifts in the absence of an MEM-induced shift. However, these responses had longer time courses than expected for MOC-induced shifts, and may have been dominated by other cochlear processes, rather than MOC Reflex. These results suggest caution in the interpretation of effects observed using ipsilaterally presented acoustic activators intended to excite the MOC Reflex.
