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1.
J Immunol Methods ; 509: 113340, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36030829

RESUMO

BACKGROUND: Detection of latent Mycobacterium tuberculosis (LTBI) in patients is important to prevent active infection and the spread of disease, particularly in vulnerable patient populations. In 2020, a kit on the high throughput Liaison XL (DiaSorin) became commercially available for the analysis of QuantiFERON-TB Gold Plus assay (Qiagen). Pilot testing indicated suboptimal repeatability of some samples with this assay. This study provides an extensive assessment of repeatability with DiaSorin system. RESULTS: Repeat testing of 481 IGRA positive samples, demonstrated substantial variability upon repeat analysis. Repeat results for TB1 and TB2 tubes, showed 73.73% and 72.82% concordance with initial results, respectively. TB1 and TB2 tube values minus the nil (IU/mL) were significantly higher in samples that were repeat positive (p < 0.001). Repeat results had better concordance with initial results if both TB1 and TB2 tubes were positive. Samples with TB1 tube values minus the nil (IU/mL) ≥ 4.54 and TB2 tube values minus the nil (IU/mL) ≥ 4.78 were found to always repeat positive. Assigning a threshold of 1.55 IU/mL for the TB1 tube value minus the nil and 1.45 IU/mL for the TB2 tube value minus the nil yielded a positive predictive value ≥95%. CONCLUSION: These results identified a potential role for retesting of select IGRA positive samples on the Diasorin Liaison XL platform due to the high proportion of samples that show a lack of repeatability. Additionally, we identified a threshold that would determine samples most likely to repeat test positive and which samples should be retested.


Assuntos
Tuberculose Latente , Mycobacterium tuberculosis , Humanos , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Tuberculose Latente/microbiologia , Luminescência , Valor Preditivo dos Testes
2.
Otol Neurotol ; 43(7): 781-788, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35763496

RESUMO

HYPOTHESIS: Characterize the contribution of the auditory nerve neurophonic (ANN) to electrocochleography (ECochG) of pediatric cochlear implant (CI) recipients with and without auditory nerve spectrum disorder (ANSD). BACKGROUND: ECochG is an emerging technique for predicting outcomes in CI recipients. Its utility may be increased by separating the cochlear microphonic (CM), produced by hair cells, from the ANN, the evoked potential correlate of neural phase-locking, which are mixed in the ongoing portion of the response to low frequency tone bursts. METHODS: Responses to tone bursts of different frequency and intensities were recorded from the round window of pediatric CI recipients. Separation of the CM and ANN was performed using a model of the underlying processes that lead to the shapes of the observed waveforms. RESULTS: Preoperative mean pure tone amplitudes of the included ANSD (n = 36) and non-ANSD subjects (n = 123), were similar (89.5 and 93.5, p = 0.1). Total of 1,024 ECochG responses to frequency and intensity series were recorded. The mean correlation ( r ) between the input and the modeled signals was 0.973 ± 0.056 (standard deviation). The ANN magnitudes were higher in the ANSD group (ANOVAs, F = 26.5 for frequency and 21.9 for intensity, df's = 1, p 's < 0.001). However, its relative contribution to the overall signal was lower (ANOVAs, F = 25.8 and 12.1, df = 1, p 's < 0.001). CONCLUSIONS: ANN was detected in low frequency ECochG responses but not high frequency responses in both ANSD and non-ANSD subjects. ANSD subjects, evidence of neural contribution in responses to low frequency stimuli was highly variable and often comparable to signals recorded in non-ANSD subjects. The computational model revealed that on average the ANN comprised a lower proportion of the overall signal than in non-ANSD subjects.


Assuntos
Implante Coclear , Implantes Cocleares , Doenças do Nervo Vestibulococlear , Audiometria de Resposta Evocada/métodos , Criança , Implante Coclear/métodos , Nervo Coclear/fisiologia , Perda Auditiva Central , Humanos
3.
Ear Hear ; 42(4): 941-948, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33369942

RESUMO

OBJECTIVES: Electrocochleography (ECochG), obtained before the insertion of a cochlear implant (CI) array, provides a measure of residual cochlear function that accounts for a substantial portion of variability in postoperative speech perception outcomes in adults. It is postulated that subsequent surgical factors represent independent sources of variance in outcomes. Prior work has demonstrated a positive correlation between angular insertion depth (AID) of straight arrays and speech perception under the CI-alone condition, with an inverse relationship observed for precurved arrays. The purpose of the present study was to determine the combined effects of ECochG, AID, and array design on speech perception outcomes. DESIGN: Participants were 50 postlingually deafened adult CI recipients who received one of three straight arrays (MED-EL Flex24, MED-EL Flex28, and MED-EL Standard) and two precurved arrays (Cochlear Contour Advance and Advanced Bionics HiFocus Mid-Scala). Residual cochlear function was determined by the intraoperative ECochG total response (TR) measured before array insertion, which is the sum of magnitudes of spectral components in response to tones of different stimulus frequencies across the speech spectrum. The AID was then determined with postoperative imaging. Multiple linear regression was used to predict consonant-nucleus-consonant (CNC) word recognition in the CI-alone condition at 6 months postactivation based on AID, TR, and array design. RESULTS: Forty-one participants received a straight array and nine received a precurved array. The AID of the most apical electrode contact ranged from 341° to 696°. The TR measured by ECochG accounted for 43% of variance in speech perception outcomes (p < 0.001). A regression model predicting CNC word scores with the TR tended to underestimate the performance for precurved arrays and deeply inserted straight arrays, and to overestimate the performance for straight arrays with shallower insertions. When combined in a multivariate linear regression, the TR, AID, and array design accounted for 72% of variability in speech perception outcomes (p < 0.001). CONCLUSIONS: A model of speech perception outcomes that incorporates TR, AID, and array design represents an improvement over a model based on TR alone. The success of this model shows that peripheral factors including cochlear health and electrode placement may play a predominant role in speech perception with CIs.


Assuntos
Implante Coclear , Implantes Cocleares , Percepção da Fala , Adulto , Audiometria de Resposta Evocada , Cóclea/cirurgia , Humanos
4.
Otol Neurotol ; 41(6): e686-e694, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32569244

RESUMO

BACKGROUND: Angular insertion depth (AID) of the electrode array provides valuable information regarding intracochlear positioning, which can be used to predict outcomes and optimize performance. While computed tomography (CT) offers high-resolution imaging, there is a need to develop technology to accurately determine AID from intraoperative x-rays acquired at unknown angles. METHODS: An algorithm was developed using a three-dimensional model of the scala tympani to estimate AID from an x-ray acquired at an unknown angle. The model is manipulated over the x-ray until the projection angle is inferred and the location of the round window and individual electrode contacts are identified. Validation of the algorithm involved 1) assessing accuracy with deviation from cochlear view by comparing AID determined with simulated x-rays to those determined with CT in a temporal bone model, and 2) assessing reproducibility in the clinical setting, by comparing intra- and inter-rater reliability with intraoperative x-ray in cochlear implant (CI) recipients, which were subsequently compared to AID determined with postoperative CT. RESULTS: Estimates of AID from x-rays were generally within 10 degrees of CT regardless of deviation from cochlear view. Excluding two outliers with poor imaging quality, the intraclass correlation coefficients for intra- and inter-rater reliability were excellent (0.991 and 0.980, respectively). CONCLUSION: With intraoperative x-rays of sufficient quality, the helical scala tympani model can be used to accurately and reliably determine AID without the need to specify a preferred image angle. The application can therefore be used in most CI recipients when a postoperative CT is not available.


Assuntos
Implante Coclear , Implantes Cocleares , Cóclea/diagnóstico por imagem , Cóclea/cirurgia , Humanos , Reprodutibilidade dos Testes , Rampa do Tímpano/diagnóstico por imagem , Rampa do Tímpano/cirurgia , Raios X
5.
J Neurophysiol ; 121(6): 2163-2180, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30943095

RESUMO

The cochlear summating potential (SP) to a tone is a baseline shift that persists for the duration of the burst. It is often considered the most enigmatic of cochlear potentials because its magnitude and polarity vary across frequency and level and its origins are uncertain. In this study, we used pharmacology to isolate sources of the SP originating from the gerbil cochlea. Animals either had the full complement of outer and inner hair cells (OHCs and IHCs) and an intact auditory nerve or had systemic treatment with furosemide and kanamycin (FK) to remove the outer hair cells. Responses to tone bursts were recorded from the round window before and after the neurotoxin kainic acid (KA) was applied. IHC responses were then isolated from the post-KA responses in FK animals, neural responses were isolated from the subtraction of post-KA from pre-KA responses in NH animals, and OHC responses were isolated by subtraction of post-KA responses in FK animals from post-KA responses in normal hearing (NH) animals. All three sources contributed to the SP; OHCs with a negative polarity and IHCs and the auditory nerve with positive polarity. Thus the recorded SP in NH animals is a sum of contributions from different sources, contributing to the variety of magnitudes and polarities seen across frequency and intensity. When this information was applied to observations of the SP recorded from the round window in human cochlear implant subjects, a strong neural contribution to the SP was confirmed in humans as well as gerbils. NEW & NOTEWORTHY Of the various potentials produced by the cochlea, the summating potential (SP) is typically described as the most enigmatic. Using combinations of ototoxins and neurotoxins, we show contributions to the SP from the auditory nerve and from inner and outer hair cells, which differ in polarity and vary in size across frequency and level. This complexity of sources helps to explain the enigmatic nature of the SP.


Assuntos
Cóclea/fisiologia , Nervo Coclear/fisiologia , Potenciais Evocados Auditivos/fisiologia , Células Ciliadas Auditivas Internas/fisiologia , Células Ciliadas Auditivas Externas/fisiologia , Adulto , Animais , Implantes Cocleares , Gerbillinae , Humanos
6.
Ear Hear ; 40(4): 833-848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30335669

RESUMO

OBJECTIVES: Electrocochleography (ECochG) obtained through a cochlear implant (CI) is increasingly being tested as an intraoperative monitor during implantation with the goal of reducing surgical trauma. Reducing trauma should aid in preserving residual hearing and improve speech perception overall. The purpose of this study was to characterize intracochlear ECochG responses throughout insertion in a range of array types and, when applicable, relate these measures to hearing preservation. The ECochG signal in cochlear implant subjects is complex, consisting of hair cell and neural generators with differing distributions depending on the etiology and history of hearing loss. Consequently, a focus was to observe and characterize response changes as an electrode advances. DESIGN: In 36 human subjects, responses to 90 dB nHL tone bursts were recorded both at the round window (RW) and then through the apical contact of the CI as the array advanced into the cochlea. The specific setup used a sterile clip in the surgical field, attached to the ground of the implant with a software-controlled short to the apical contact. The end of the clip was then connected to standard audiometric recording equipment. The stimuli were 500 Hz tone bursts at 90 dB nHL. Audiometry for cases with intended hearing preservation (12/36 subjects) was correlated with intraoperative recordings. RESULTS: Successful intracochlear recordings were obtained in 28 subjects. For the eight unsuccessful cases, the clip introduced excessive line noise, which saturated the amplifier. Among the successful subjects, the initial intracochlear response was a median 5.8 dB larger than the response at the RW. Throughout insertion, modiolar arrays showed median response drops after stylet removal while in lateral wall arrays the maximal median response magnitude was typically at the deepest insertion depth. Four main patterns of response magnitude were seen: increases > 5 dB (12/28), steady responses within 5 dB (4/28), drops > 5 dB (from the initial response) at shallow insertion depths (< 15 mm deep, 7/28), or drops > 5 dB occurring at deeper depths (5/28). Hearing preservation, defined as < 80 dB threshold at 250 Hz, was successful in 9/12 subjects. In these subjects, an intracochlear loss of response magnitude afforded a prediction model with poor sensitivity and specificity, which improved when phase, latency, and proportion of neural components was considered. The change in hearing thresholds across cases was significantly correlated with various measures of the absolute magnitudes of response, including RW response, starting response, maximal response, and final responses (p's < 0.05, minimum of 0.0001 for the maximal response, r's > 0.57, maximum of 0.80 for the maximal response). CONCLUSIONS: Monitoring the cochlea with intracochlear ECochG during cochlear implantation is feasible, and patterns of response vary by device type. Changes in magnitude alone did not account for hearing preservation rates, but considerations of phase, latency, and neural contribution can help to interpret the changes seen and improve sensitivity and specificity. The correlation between the absolute magnitude obtained either before or during insertion of the ECochG and the hearing threshold changes suggest that cochlear health, which varies by subject, plays an important role.


Assuntos
Audiometria de Resposta Evocada/métodos , Cóclea/fisiopatologia , Implante Coclear/métodos , Perda Auditiva Neurossensorial/reabilitação , Monitorização Intraoperatória/métodos , Percepção da Fala , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Cóclea/cirurgia , Implantes Cocleares , Feminino , Audição , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Janela da Cóclea , Adulto Jovem
7.
Ear Hear ; 39(6): 1146-1156, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29554036

RESUMO

OBJECTIVES: Electrocochleography is increasingly being utilized as an intraoperative monitor of cochlear function during cochlear implantation (CI). Intracochlear recordings from the advancing electrode can be obtained through the device by on-board capabilities. However, such recordings may not be ideal as a monitor because the recording electrode moves in relation to the neural and hair cell generators producing the responses. The purposes of this study were to compare two extracochlear recording locations in terms of signal strength and feasibility as intraoperative monitoring sites and to characterize changes in cochlear physiology during CI insertion. DESIGN: In 83 human subjects, responses to 90 dB nHL tone bursts were recorded both at the round window (RW) and then at an extracochlear position-either adjacent to the stapes or on the promontory just superior to the RW. Recording from the fixed, extracochlear position continued during insertion of the CI in 63 cases. RESULTS: Before CI insertion, responses to low-frequency tones at the RW were roughly 6 dB larger than when recording at either extracochlear site, but the two extracochlear sites did not differ from one another. During CI insertion, response losses from the promontory or adjacent to the stapes stayed within 5 dB in ≈61% (38/63) of cases, presumably indicating atraumatic insertions. Among responses which dropped more than 5 dB at any time during CI insertion, 12 subjects showed no response recovery, while in 13, the drop was followed by partial or complete response recovery by the end of CI insertion. In cases with recovery, the drop in response occurred relatively early (<15 mm insertion) compared to those where there was no recovery. Changes in response phase during the insertion occurred in some cases; these may indicate a change in the distributions of generators contributing to the response. CONCLUSIONS: Monitoring the electrocochleography during CI insertion from an extracochlear site reveals insertions that are potentially atraumatic, show interaction with cochlear structures followed by response recovery, or show interactions such that response losses persist to the end of recording.


Assuntos
Audiometria de Resposta Evocada , Implante Coclear/métodos , Implantes Cocleares , Monitorização Intraoperatória , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Janela da Cóclea , Adulto Jovem
8.
Front Neurosci ; 11: 592, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29123468

RESUMO

Electrocochleography (ECochG) is a potential clinically valuable technique for predicting speech perception outcomes in cochlear implant (CI) recipients, among other uses. Current analysis is limited by an inability to quantify hair cell and neural contributions which are mixed in the ongoing part of the response to low frequency tones. Here, we used a model based on source properties to account for recorded waveform shapes and to separate the combined signal into its components. The model for the cochlear microphonic (CM) was a sinusoid with parameters for independent saturation of the peaks and the troughs of the responses. The model for the auditory nerve neurophonic (ANN) was the convolution of a unit potential and population cycle histogram with a parameter for spread of excitation. Phases of the ANN and CM were additional parameters. The average cycle from the ongoing response was the input, and adaptive fitting identified CM and ANN parameters that best reproduced the waveform shape. Test datasets were responses recorded from the round windows of CI recipients, from the round window of gerbils before and after application of neurotoxins, and with simulated signals where each parameter could be manipulated in isolation. Waveforms recorded from 284 CI recipients had a variety of morphologies that the model fit with an average r2 of 0.97 ± 0.058 (standard deviation). With simulated signals, small systematic differences between outputs and inputs were seen with some variable combinations, but in general there were limited interactions among the parameters. In gerbils, the CM reported was relatively unaffected by the neurotoxins. In contrast, the ANN was strongly reduced and the reduction was limited to frequencies of 1,000 Hz and lower, consistent with the range of strong neural phase-locking. Across human CI subjects, the ANN contribution was variable, ranging from nearly none to larger than the CM. Development of this model could provide a means to isolate hair cell and neural activity that are mixed in the ongoing response to low-frequency tones. This tool can help characterize the residual physiology across CI subjects, and can be useful in other clinical settings where a description of the cochlear physiology is desirable.

9.
Otol Neurotol ; 38(10): 1415-1420, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28953607

RESUMO

HYPOTHESIS: Intraoperative, intracochlear electrocochleography (ECochG) will provide a means to monitor cochlear hair cell and neural response during cochlear implant (CI) electrode insertion. Distinct patterns in the insertion track can be characterized. BACKGROUND: Conventional CI surgery is performed without a means of actively monitoring cochlear hair cell and neural responses. Intracochlear ECochG obtained directly through the CI may be a source of such feedback. Understanding the patterns observed in the "insertion track" is an essential step toward refining intracochlear ECochG as a tool that can be used to assist in intraoperative decision making and prognostication of hearing preservation. METHODS: Intracochlear ECochG was performed in 17 patients. During electrode insertion, a 50-ms tone burst acoustic stimulus was delivered with a frequency of 500 Hz at 110 dB SPL. The ECochG response was monitored from the apical-most electrode. The amplitude of the first harmonic was plotted and monitored in near real time by the audiologist-surgeon team during CI electrode insertion. RESULTS: Three distinct patterns in first harmonic amplitude change were observed across subjects during insertion: Type A (52%), overall increase in amplitude from the beginning of insertion until completion; Type B (11%), a maximum amplitude at the beginning of insertion, with a decrease in amplitude as insertion progressed to completion; and Type C (35%), comparable amplitudes at the beginning and completion of the insertion with the maximum amplitude mid-insertion. CONCLUSION: Three ECochG patterns were observed during electrode advancement into the cochlea. Ongoing and future work will broaden our scope of knowledge regarding the relationship among these patterns, the presence of cochlear trauma, and functional outcomes related to hearing preservation.


Assuntos
Audiometria de Resposta Evocada/métodos , Implante Coclear/métodos , Monitorização Neurofisiológica Intraoperatória/métodos , Adulto , Criança , Cóclea/cirurgia , Implantes Cocleares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Front Neurosci ; 11: 416, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28769753

RESUMO

Auditory neuropathy spectrum disorder (ANSD) is characterized by an apparent discrepancy between measures of cochlear and neural function based on auditory brainstem response (ABR) testing. Clinical indicators of ANSD are a present cochlear microphonic (CM) with small or absent wave V. Many identified ANSD patients have speech impairment severe enough that cochlear implantation (CI) is indicated. To better understand the cochleae identified with ANSD that lead to a CI, we performed intraoperative round window electrocochleography (ECochG) to tone bursts in children (n = 167) and adults (n = 163). Magnitudes of the responses to tones of different frequencies were summed to measure the "total response" (ECochG-TR), a metric often dominated by hair cell activity, and auditory nerve activity was estimated visually from the compound action potential (CAP) and auditory nerve neurophonic (ANN) as a ranked "Nerve Score". Subjects identified as ANSD (45 ears in children, 3 in adults) had higher values of ECochG-TR than adult and pediatric subjects also receiving CIs not identified as ANSD. However, nerve scores of the ANSD group were similar to the other cohorts, although dominated by the ANN to low frequencies more than in the non-ANSD groups. To high frequencies, the common morphology of ANSD cases was a large CM and summating potential, and small or absent CAP. Common morphologies in other groups were either only a CM, or a combination of CM and CAP. These results indicate that responses to high frequencies, derived primarily from hair cells, are the main source of the CM used to evaluate ANSD in the clinical setting. However, the clinical tests do not capture the wide range of neural activity seen to low frequency sounds.

11.
Int J Pediatr Otorhinolaryngol ; 99: 120-127, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28688553

RESUMO

OBJECTIVES: To assess electrocochleography (ECochG) to tones as an instrument to account for CI speech perception outcomes in children with auditory neuropathy spectrum disorder (ANSD). MATERIALS & METHODS: Children (<18 years) receiving CIs for ANSD (n = 30) and non-ANSD (n = 74) etiologies of hearing loss were evaluated with ECochG using tone bursts (0.25-4 kHz). The total response (TR) is the sum of spectral peaks of responses across frequencies. The compound action potential (CAP) and the auditory nerve neurophonic (ANN) in ECochG waveforms were used to estimate nerve activity and calculate nerve score. Performance on open-set monosyllabic word tests was the outcome measure. Standard statistical methods were applied. RESULTS: On average, TR was larger in ANSD than in non-ANSD subjects. Most ANSD (73.3%) and non-ANSD (87.8%) subjects achieved open-set speech perception; TR accounted for 33% and 20% of variability in the outcomes, respectively. In the ANSD group, the PTA accounted for 69.3% of the variability, but there was no relationship with outcomes in the non-ANSD group. In both populations, nerve score was sensitive in identifying subjects at risk for not acquiring open-set speech perception, while the CAP and the ANN were more specific. CONCLUSION: In both subject groups, the TRs correlated with outcomes but these measures were notably larger in the ANSD group. There was also strong correlation between PTA and speech perception outcome in ANSD group. In both subject populations, weaker evidence of neural activity was related to failure to achieve open-set speech perception.


Assuntos
Audiometria de Resposta Evocada/métodos , Implante Coclear/métodos , Perda Auditiva Central/fisiopatologia , Percepção da Fala/fisiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Surdez/fisiopatologia , Surdez/cirurgia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Doenças do Nervo Vestibulococlear/cirurgia
12.
Otol Neurotol ; 37(10): 1654-1661, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27749750

RESUMO

HYPOTHESIS: The compound action potential (CAP) is a purely neural component of the cochlea's response to sound, and may provide information regarding the existing neural substrate in cochlear implant (CI) subjects that can help account for variance in speech perception outcomes. BACKGROUND: Measurement of the "total response" (TR), or sum of the magnitudes of spectral components in the ongoing responses to tone bursts across frequencies, has been shown to account for 40 to 50% of variance in speech perception outcomes. The ongoing response is composed of both hair cell and neural components. This correlation may be improved with the addition of the CAP. METHODS: Intraoperative round window electrocochleography (ECochG) was performed in adult and pediatric CI subjects (n = 238). Stimuli were tones of different frequencies (250 Hz-4 kHz) at 90 dB nHL. The CAP was assessed in two ways, as an amplitude and with a scaling factor derived from a function fitted to the response. The results were correlated with consonant-nucleus-consonant (CNC) word scores at 6 months post-implantation (n = 51). RESULTS: Only about half of the subjects had a measurable CAP at any frequency. The CNC word scores correlated weakly with both amplitude (r = 0.20, p < 0.001) and scaling factor (r = 0.25, p < 0.01). In contrast, the TR alone accounted for 43% of the variance, and addition of either CAP measurement in multiple regression did not account for additional variance. CONCLUSIONS: The underlying pathology in CI patients causes the CAP to be often absent and highly variable when present. The TR is a better predictor of speech perception outcomes than the CAP.


Assuntos
Potenciais de Ação/fisiologia , Audiometria de Resposta Evocada/métodos , Cóclea/fisiologia , Implante Coclear , Monitorização Neurofisiológica Intraoperatória/métodos , Adulto , Criança , Cóclea/cirurgia , Implante Coclear/métodos , Implantes Cocleares , Feminino , Humanos , Masculino , Análise Multivariada , Janela da Cóclea/cirurgia , Percepção da Fala/fisiologia , Resultado do Tratamento
13.
Laryngoscope ; 126(5): 1193-200, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26360623

RESUMO

OBJECTIVE/HYPOTHESIS: Previous reports have documented the feasibility of utilizing electrocochleographic (ECoG) responses to acoustic signals to assess trauma caused during cochlear implantation. The hypothesis is that intraoperative round window ECoG before and after electrode insertion will help predict postoperative hearing preservation outcomes in cochlear implant recipients. STUDY DESIGN: Prospective cohort study. METHODS: Intraoperative round window ECoG responses were collected from 31 cochlear implant recipients (14 children and 17 adults) immediately prior to and just after electrode insertion. Hearing preservation was determined by postoperative changes in behavioral thresholds. RESULTS: On average, the postinsertion response was smaller than the preinsertion response by an average of 4 dB across frequencies. However, in some cases (12 of 31) the response increased after insertion. The subsequent hearing loss was greater than the acute loss in the ECoG, averaging 22 dB across the same frequency range (250-1,000 Hz). There was no correlation between the change in the ECoG response and the corresponding change in audiometric threshold. CONCLUSIONS: Intraoperative ECoG is a sensitive method for detecting electrophysiologic changes during implantation but had limited prognostic value regarding hearing preservation in the current conventional cochlear implant patient population where hearing preservation was not intended. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:1193-1200, 2016.


Assuntos
Audiometria de Resposta Evocada , Implante Coclear , Perda Auditiva/cirurgia , Monitorização Intraoperatória/métodos , Janela da Cóclea/fisiologia , Adulto , Idoso , Limiar Auditivo , Criança , Pré-Escolar , Implante Coclear/métodos , Implantes Cocleares , Feminino , Perda Auditiva/diagnóstico , Perda Auditiva/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
14.
BMC Cancer ; 12: 145, 2012 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-22494660

RESUMO

BACKGROUND: Among American men, prostate cancer is the most common, non-cutaneous malignancy that accounted for an estimated 241,000 new cases and 34,000 deaths in 2011. Previous studies have suggested that Wnt pathway inhibitory genes are silenced by CpG hypermethylation, and other studies have suggested that genistein can demethylate hypermethylated DNA. Genistein is a soy isoflavone with diverse effects on cellular proliferation, survival, and gene expression that suggest it could be a potential therapeutic agent for prostate cancer. We undertook the present study to investigate the effects of genistein on the epigenome of prostate cancer cells and to discover novel combination approaches of other compounds with genistein that might be of translational utility. Here, we have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial to mesenchymal transition (EMT), to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. METHODS: Using whole genome expression profiling and whole genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and combination treatment, where cell death and cell proliferation was determined. RESULTS: Contrary to earlier reports, genistein did not have an effect on CpG methylation at 20 µM, but it did affect histone H3K9 acetylation and induced increased expression of histone acetyltransferase 1 (HAT1). In addition, genistein also had differential effects on survival and cooperated with the histone deacteylase inhibitor vorinostat to induce cell death and inhibit proliferation. CONCLUSION: Our results suggest that there are a number of pathways that are affected with genistein and vorinostat treatment such as Wnt, TNF, G2/M DNA damage checkpoint, and androgen signaling pathways. In addition, genistein cooperates with vorinostat to induce cell death in prostate cancer cell lines with a greater effect on early stage prostate cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose , Genisteína/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Neoplasias da Próstata/genética , Inibidores de Proteínas Quinases/farmacologia , Acetilação , Idoso , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Análise por Conglomerados , Dano ao DNA/efeitos dos fármacos , Metilação de DNA , Sinergismo Farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Vorinostat
15.
Biotechnol Prog ; 25(4): 1169-75, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19562742

RESUMO

Electrospinning is a useful technique that can generate micro and nanometer-sized fibers. Modification of the electrospinning parameters, such as deposition target geometry, can generate uniaxially aligned fibers for use in diverse applications ranging from tissue engineering to material fabrication. For example, meshes of fibers have been shown to mimic the extracellular matrix networks for use in smooth muscle cell proliferation. Further, aligned fibers can guide neurites to grow along the direction of the fibers. Here we present a novel electrospinning deposition target that combines the benefits of two previously reported electrodes: the standard parallel electrodes and the spinning wheel with a sharpened edge. This new target design significantly improves aligned fiber yield. Specifically, the target consists of two parallel aluminum plates with sharpened edges containing a bifurcating angle of 26 degrees. Electric field computations show a larger probable area of aligned electric field vectors. This new deposition target allows fibers to deposit on a larger cross-sectional area relative to the existing parallel electrode and at least doubles the yield of uniaxially aligned fibers. Further, fiber alignment and morphology are preserved after collection from the deposition target.


Assuntos
Materiais Biocompatíveis/química , Técnicas Eletroquímicas/métodos , Alicerces Teciduais/química , Propriedades de Superfície
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