Adverse effects of pesticides on central auditory functions in tobacco growers.

OBJECTIVE: To investigate the effects of exposure to pesticides on the central auditory functions (CAF) of Brazilian tobacco growers. DESIGN: This was a cross-sectional study carried out between 2010 and 2012. Participants were evaluated with two behavioural procedures to investigate CAF, the random gap detection test (RGDT) and the dichotic digit test in Portuguese (DDT). STUDY SAMPLE: A total of 22 growers exposed to pesticides (study group) and 21 subjects who were not exposed to pesticides (control group) were selected. RESULTS: No significant differences between groups were observed for pure-tone thresholds. A significant association between pesticide exposure and the results for RGDT and DDT was found. Significant differences between pesticide-exposed and nonexposed subjects were found for RGDT frequency average and DDT binaural average, when including age and hearing level as covariates. Age was significantly associated with RGDT frequency average, DDT left ear score, DDT binaural average and DDT right ear advantage. Hearing levels were not significantly associated with any of the test scores. The relative risk of failing the DDT and RGDT for the study group was 1.88 (95% CI: 1.10-3.20) and 1.74 (95% CI: 1.06-2.86), respectively, as compared with the control group. CONCLUSIONS: The results showed that tobacco growers exposed to pesticides exhibited signs of central auditory dysfunction characterised by decrements in temporal processing and binaural integration processes/abilities.

Inhalation of Hydrocarbon Jet Fuel Suppress Central Auditory Nervous System Function.

More than 800 million L/d of hydrocarbon fuels is used to power cars, boats, and jet airplanes. The weekly consumption of these fuels necessarily puts the public at risk for repeated inhalation exposure. Recent studies showed that exposure to hydrocarbon jet fuel produces lethality in presynaptic sensory cells, leading to hearing loss, especially in the presence of noise. However, the effects of hydrocarbon jet fuel on the central auditory nervous system (CANS) have not received much attention. It is important to investigate the effects of hydrocarbons on the CANS in order to complete current knowledge regarding the ototoxic profile of such exposures. The objective of the current study was to determine whether inhalation exposure to hydrocarbon jet fuel might affect the functions of the CANS. Male Fischer 344 rats were randomly divided into four groups (control, noise, fuel, and fuel + noise). The structural and functional integrity of presynaptic sensory cells was determined in each group. Neurotransmission in both peripheral and central auditory pathways was simultaneously evaluated in order to identify and differentiate between peripheral and central dysfunctions. There were no detectable effects on pre- and postsynaptic peripheral functions. However, the responsiveness of the brain was significantly depressed and neural transmission time was markedly delayed. The development of CANS dysfunctions in the general public and the military due to cumulative exposure to hydrocarbon fuels may represent a significant but currently unrecognized public health issue.

Exposure to low levels of jet-propulsion fuel impairs brainstem encoding of stimulus intensity.

Jet propulsion fuel-8 (JP-8) is a kerosene-based fuel that is used in military jets. The U.S. Armed Services and North Atlantic Treaty Organization countries adopted JP-8 as a standard fuel source and the U.S. military alone consumes more than 2.5 billion gallons annually. Preliminary epidemiologic data suggested that JP-8 may interact with noise to induce hearing loss, and animal studies revealed damage to presynaptic sensory cells in the cochlea. In the current study, Long-Evans rats were divided into four experimental groups: control, noise only, JP-8 only, and JP-8 + noise. A subototoxic level of JP-8 was used alone or in combination with a nondamaging level of noise. Functional and structural assays of the presynaptic sensory cells combined with neurophysiologic studies of the cochlear nerve revealed that peripheral auditory function was not affected by individual exposures and there was no effect when the exposures were combined. However, the central auditory nervous system exhibited impaired brainstem encoding of stimulus intensity. These findings may represent important and major shifts in the theoretical framework that governs current understanding of jet fuel and/or jet fuel + noise-induced ototoxicity. From an epidemiologic perspective, results indicate that jet fuel exposure may exert consequences on auditory function that may be more widespread and insidious than what was previously shown. It is possible that a large population of military personnel who are suffering from the effects of jet fuel exposure may be misidentified because they would exhibit normal hearing thresholds but harbor a "hidden" brainstem dysfunction.

[Peripheral and central auditory effects of pesticide exposure: a systematic review]. / Efeitos da exposição a agrotóxicos sobre o sistema auditivo periférico e central: uma revisão sistemática.

The World Health Organization reports a total of 3 million annual cases of acute pesticide poisoning (2.1 million cases in the developing countries alone). Pesticide use has reached alarming proportions in Brazil in the last decade. Pesticide sales skyrocketed from 2001 to 2008, making Brazil the world's leading consumer of poisons. This study aimed to assess whether pesticide exposure causes peripheral or central auditory disorders and thus focused on the importance of hearing tests in populations with acute or chronic exposure. This was a systematic review of studies on the effects of pesticide exposure on the auditory system. The context and methodological quality of the full texts were analyzed. The review identified 143 studies on the theme, 16 of which met the inclusion criteria. All articles showed that pesticide exposure is ototoxic and leads to hearing loss.

Efeitos da exposição a agrotóxicos sobre o sistema auditivo periférico e central: uma revisão sistemática / Peripheral and central auditory effects of pesticide exposure: a systematic review / Efectos de la exposición a los pesticidas en el sistema auditivo periférico y central: una revisión sistemática

De acordo com a Organização Mundial da Saúde, as intoxicações agudas por agrotóxicos são da ordem de 3 milhões anuais, com 2,1 milhões de casos só nos países em desenvolvimento. Na última década, no Brasil, o uso de agrotóxicos assumiu proporções assustadoras. Entre 20012008 a venda desses produtos saltou, quando o país alcançou a posição de maior consumidor mundial de venenos. O objetivo deste estudo foi avaliar por meio de uma revisão sistemática se a exposição ao agrotóxico causa alterações auditivas no sistema auditivo periférico/central, atentando assim para a importância da avaliação auditiva em populações expostas de forma crônica ou aguda. Trata-se de uma revisão sistemática dos estudos publicados sobre os efeitos da exposição ao agrotóxico no sistema auditivo. Analisaram-se os trabalhos contemplados na íntegra e também sua qualidade metodológica. A pesquisa identificou 143 estudos sobre o tema, sendo que 16 se enquadraram nos critérios de inclusão. Todos os artigos analisados evidenciaram que a exposição ao agrotóxico é ototóxica e induz ao dano às vias auditivas.

The World Health Organization reports a total of 3 million annual cases of acute pesticide poisoning (2.1 million cases in the developing countries alone). Pesticide use has reached alarming proportions in Brazil in the last decade. Pesticide sales skyrocketed from 2001 to 2008, making Brazil the world's leading consumer of poisons. This study aimed to assess whether pesticide exposure causes peripheral or central auditory disorders and thus focused on the importance of hearing tests in populations with acute or chronic exposure. This was a systematic review of studies on the effects of pesticide exposure on the auditory system. The context and methodological quality of the full texts were analyzed. The review identified 143 studies on the theme, 16 of which met the inclusion criteria. All articles showed that pesticide exposure is ototoxic and leads to hearing loss.

El objetivo de este artículo es presentar un estudio sobre el uso de la historia oral de vida como estrategia de aproximación entre cuidador y anciano, con el fin de contribuir a la humanización en la relación entre el profesional de la salud y el paciente. Se trata de una investigación cualitativa y descriptiva. Hemos reunido a siete ancianos, varones y mujeres, con más de 65 años que, a partir de entrevistas abiertas y semi-estructuradas, hicieron posible la producción de relatos de vida que, una vez finalizados, fueron devueltos a los colaboradores en forma de cuadernos personalizados para que ellos dispusieran de ellos como quisieran. Como resultado ha sido posible percibir que tal metodología contribuye a la generación de un vínculo entre enfermero y anciano, presentándose no solamente como elemento humanizador, sino también terapéutico.

Xylene-induced auditory dysfunction in humans.

OBJECTIVES: Animal data indicate that xylene induces cochlear dysfunction, characterized by the loss of outer hair cells. There is little evidence regarding xylene-induced ototoxicity in humans. The aim of the study was to investigate the possible adverse effects of xylene on the peripheral and central auditory system in humans. DESIGN: A total of 30 medical laboratory workers who had been exposed to a mixture of xylene isomers, together with 30 nonexposed control participants matched for gender, age, and educational level were selected. Participants of both groups were not exposed to noise levels above 85 dBA time-weighted average. All participants were evaluated with a comprehensive audiological test battery, which included measures of peripheral and central auditory function. Peripheral auditory measures included pure-tone audiometry and distortion product otoacoustic emissions. Behavioral measures of central auditory function included a pitch pattern sequence test, an adaptive test of temporal resolution, a dichotic digit test, and a masking level difference test. The auditory brainstem response was used to objectively evaluate the function of the auditory pathways at the brainstem level. Speech perception in quiet and in noise was evaluated using the Hearing In Noise Test (HINT). The xylene-exposed participants were extensively evaluated with regard to their exposure to both noise and xylene. Noise dosimetry was conducted over an 8-hr work shift to obtain noise-exposure levels for each xylene-exposed worker. Airborne xylene concentrations were obtained at 11 different workstations throughout the medical laboratories, and methyl hippuric acid levels per gram of creatinine in urine were obtained for each xylene-exposed subject. Finally, a detailed interview exploring current and past solvent and noise exposure was conducted. RESULTS: The xylene-exposed participants showed significantly worse pure-tone thresholds in comparison with the nonexposed participants. The xylene-exposed participants demonstrated significantly worse results than the control group participants for the pitch pattern sequence test, dichotic digit test, HINT, and the auditory brainstem response (absolute and interpeak latencies). No significant differences between the xylene-exposed and nonexposed participants were observed for distortion product otoacoustic emissions, adaptive test of temporal resolution, or the masking level difference test. A significant correlation between the concentrations of methyl hippuric acid in urine and pure-tone thresholds (2 to 8 kHz) was found in xylene-exposed workers. Also, participants with high cumulative dose of xylene exposure presented with poorer test results than participants with low cumulative dose of xylene exposure. CONCLUSIONS: The results of the present research suggest that xylene is associated with adverse central auditory effects and poorer sound detection abilities in humans. A major limitation of the study is that the results found among xylene-exposed participants cannot be proved to be permanent, and thus further research should be conducted to clarify this limitation. Workers exposed to this chemical should be routinely evaluated with a comprehensive audiological test battery, to detect early signs of auditory dysfunction.

Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats.

Antenatal corticosteroid (AC) treatment is given to pregnant women at risk for preterm birth to reduce infant morbidity and mortality by enhancing lung and brain maturation. However, there is no accepted regimen on how frequently AC treatments should be given and some studies found that repeated AC treatments can cause growth retardation and brain damage. Our goal was to assess the dose-dependent effects of repeated AC treatment and estimate the critical number of AC courses to cause harmful effects on the auditory brainstem response (ABR), a sensitive measure of brain development, neural transmission and hearing loss. We hypothesized that repeated AC treatment would have harmful effects on the offspring's ABRs and growth only if more than 3 AC treatment courses were given. To test this hypothesis, pregnant Wistar rats were given either a high regimen of AC (HAC), a moderate regimen (MAC), a low regimen (LAC), or saline (SAL). An untreated control (CON) group was also used. Simulating the clinical condition, the HAC dams received 0.2mg/kg Betamethasone (IM) twice daily for 6 days during gestation days (GD) 17-22. The MAC dams received 3 days of AC treatment followed by 3 days of saline treatment on GD 17-19 and GD 20-22, respectively. The LAC dams received 1 day of AC treatment followed by 5 days of saline treatment on GD 17 and GD 18-22, respectively. The SAL dams received 6 days of saline treatment from GD 17 to 22 (twice daily, isovolumetric to the HAC injections, IM). The offspring were ABR-tested on postnatal day 24. Results indicated that the ABR's P4 latencies (neural transmission time) were significantly prolonged (worse) in the HAC pups and that ABR's thresholds were significantly elevated (worse) in the HAC and MAC pups when compared to the CON pups. The HAC and MAC pups were also growth retarded and had higher postnatal mortality than the CON pups. The SAL and LAC pups showed little or no adverse effects. In conclusion, repeated AC treatment had harmful effects on the rat offspring's ABRs, postnatal growth and survival. The prolonged ABR latencies reflect slowed neural transmission times along the auditory nerve and brainstem auditory pathway. The elevated ABR thresholds reflect hearing deficits. We concluded that repeated AC treatment can have harmful neurological, sensory and developmental effects on the rat offspring. These effects should be considered when weighing the benefits and risks of repeated AC treatment and when monitoring and managing the prenatally exposed child for possible adverse effects.

Central auditory dysfunction associated with exposure to a mixture of solvents.

OBJECTIVE: The aim of the present research was to investigate central auditory functioning in normal-hearing, solvent-exposed subjects compared to normal-hearing subjects without solvent exposure, with a comprehensive test battery of behavioural central auditory functioning procedures. STUDY SAMPLE: Forty-six normal-hearing, solvent-exposed subjects and 46 normal-hearing, control subjects were selected to participate in the study. DESIGN: All subjects must present with normal hearing thresholds and absence of history of variables related to the onset of auditory dysfunction. Subjects were evaluated with a test battery comprising pure-tone audiometry (PTA), dichotic digits (DD), pitch pattern sequence (PPS), filtered speech (FS), random gap detection (RGD), masking level difference (MLD), and hearing-in-noise (HINT) tests. RESULTS: Analyses of covariance (ANCOVA) were performed to compare the mean values of the dependent variables (results for DD, PPS, FS, RGD, MLD, and HINT) between solvent-exposed and control subjects. Age and average hearing thresholds (500-8000 Hz) were included in the analyses as covariates. Significant differences for DD, PPS, FS, and RGD results were found between groups. CONCLUSION: This study provides further evidence of the central auditory dysfunction associated with solvent exposure.

Effects of amikacin on maturation of the auditory analyzer in rabbits.

We studied the dynamics of maturation of the hearing function by records of short-term latent brainstem evoked potentials and the effect of amikacin on maturation of the hearing function. The peripheral compartment of the auditory analyzer matures sooner than the central structures. Amikacin in therapeutic doses exhibited an ototoxic effect on the peripheral compartment of the auditory analyzer without impairing its central structures.

Synchronous auditory nerve activity in the carboplatin-chinchilla model of auditory neuropathy.

Two hallmark features of auditory neuropathy (AN) are normal outer hair cell function in the presence of an absent/abnormal auditory brainstem response (ABR). Studies of human AN patients are unable to determine whether disruption of the ABR is the result of a reduction of neural input, a loss of auditory nerve fiber (ANF) synchrony, or both. Neurophysiological data from the carboplatin model of AN reveal intact neural synchrony in the auditory nerve and inferior colliculus, despite significant reductions in neural input. These data suggest that (1), intact neural synchrony is available to support an ABR following carboplatin treatment and, (2), impaired spike timing intrinsic to neurons is required for the disruption of the ABR observed in human AN.

Inactivation of the left auditory cortex impairs temporal discrimination in the rat.

The left auditory cortex (AC) in humans is involved in the processing of the temporal parameters of acoustical signals, specifically in speech perception, whereas the right AC plays the dominant role in pitch and melody perception. The hemispheric lateralization of acoustical signal processing in non-human mammals is less explored. The present study examined the ability of rats to detect or discriminate a series of gaps in continuous noise under conditions of unilateral or bilateral reversible inactivation of the AC. The results showed that muscimol-induced reversible inactivation of the left AC suppresses the ability of rats to discriminate between acoustical stimuli of different temporal parameters (duration or repetition rate), whereas inactivation of the right AC results in no change or only a mild decrease in discrimination ability. Hemispheric asymmetry was observed only in the case of gap discrimination tasks, but not in a gap detection task. Our findings demonstrate that, similarly as in humans, the left AC in the rat plays the dominant role in temporal discrimination. These data provide further evidence for the functional asymmetry of the mammalian brain, which appears in a relatively early phase of evolution.

Acute auditory and vestibular symptoms associated with heat and transdermal lidocaine.

OBJECTIVES: To describe a case of systemic lidocaine toxicity from the simultaneous use of transdermal patches and a heating pad. METHODS: Case report and discussion. RESULTS: The focus of this case report are the interesting neuro-otologic signs of central lidocaine toxicity that occurred after a patient fell asleep on a heating pad with his Lidoderm patches in place. Hearing improvement, tinnitus reduction, and severe dizziness and ataxia were present for approximately 48 hours before spontaneous resolution. Based upon his symptoms we estimate an 11-fold increase in plasma concentrations of lidocaine. DISCUSSION: Transdermal delivery of medication affords ease of application, ability to provide continuous pharmacological therapy, and ability to supply medication to the affected site. Due to the superficial application of these medications, external environmental factors may influence the pharmacokinetics of drug delivery. This case highlights the complications that can arise from the combination of heating pads and transdermal pain therapies.

Peripheral and central auditory dysfunction induced by occupational exposure to organic solvents.

OBJECTIVE: To examine the effects of solvent exposure on hearing function, through an audiological test battery, in a population not occupationally exposed to high levels of noise. METHODS: One hundred ten workers from a coating factory were studied. Jobs at the factory were divided into three different levels of solvent exposure. Hearing status was assessed with a test battery including pure-tone hearing thresholds (0.5-8 kHz), high-frequency hearing thresholds (12 and 16 kHz), and dichotic listening measured through dichotic digits test. Multiple linear regression models were created to explore possible association between solvent exposure and each of the hearing outcomes. RESULTS: Significant associations between solvent exposure and the three hearing outcomes were found. Covariates such as age, gender, race, and ethnicity were also significantly associated with the studied hearing outcomes. CONCLUSIONS: Occupational exposure to solvents may induce both peripheral and central auditory dysfunction. The dichotic digits test seems as a sensible tool to detect central auditory dysfunction associated with solvent exposure. Hearing loss prevention programs may use this tool to monitor hearing in solvent-exposed workers.

Evaluation of inner hair cell and nerve fiber loss as sufficient pathologies underlying auditory neuropathy.

Auditory neuropathy is a hearing disorder characterized by normal function of outer hair cells, evidenced by intact cochlear microphonic (CM) potentials and otoacoustic emissions (OAEs), with absent or severely dys-synchronized auditory brainstem responses (ABRs). To determine if selective lesions of inner hair cells (IHCs) and auditory nerve fibers (ANFs) can account for these primary clinical features of auditory neuropathy, we measured physiological responses from chinchillas with large lesions of ANFs (about 85%) and IHCs (45% loss in the apical half of the cochlea; 73% in the basal half). Distortion product OAEs and CM potentials were significantly enhanced, whereas summating potentials and compound action potentials (CAPs) were significantly reduced. CAP threshold was elevated by 7.5dB, but response synchrony was well preserved down to threshold levels of stimulation. Similarly, ABR threshold was elevated by 5.6dB, but all waves were present and well synchronized down to threshold levels in all animals. Thus, large lesions of IHCs and ANFs reduced response amplitudes but did not abolish or severely dys-synchronize CAPs or ABRs. Pathologies other than or in addition to ANF and IHC loss are likely to account for the evoked potential dys-synchrony that is a clinical hallmark of auditory neuropathy in humans.

Central auditory damage induced by solvent exposure.

Different studies have demonstrated that solvents may induce auditory damage. It has been suggested that part of this damage may be localised in central auditory pathways. The present study aimed to investigate possible auditory processing disorders related to solvent exposure. Thirty solvent-exposed workers and 30 gender-, age- and educational level-matched control subjects were selected to participate in the study. To select participants, a questionnaire, otoscopy, pure-tone audiometry and tympanometry were carried out. Filtered speech (FS), random gap detection (RGD) and hearing-in-noise tests (HINT) were conducted in the selected participants. Both groups of workers presented as a mean normal hearing thresholds. However, significant differences between groups were observed for RGD, FS and HINT. It is concluded that a possible auditory processing disorder may be related to solvent exposure.

Fetal central auditory system metabolic response to cochlear implant stimulation.

OBJECTIVES: The purpose of this study was to examine the effects of profound auditory deprivation and its treatment by cochlear implantation and stimulation on the metabolic activity of the central auditory system in fetal sheep. METHODS: Six ovine fetuses at 85% to 90% gestation were bilaterally deafened by kanamycin perfusion and unilaterally implanted with cochlear electrode arrays. Half of the implanted animals were stimulated with an extrauterine sound processor, and half were not. Four animals served as hearing controls. One week postoperatively, central nervous system metabolic activity was evaluated in ambient laboratory noise by quantitative autoradiography using (14)C-deoxyglucose. RESULTS: Kanamycin perfusion deafened all treated animals as verified by auditory brainstem response and scanning electron microscopy. Glucose utilization in the inferior colliculus was markedly lower in deafened and unstimulated animals relative to hearing controls. Glucose utilization in implanted-stimulated animals was similar to normal controls. CONCLUSIONS: Changes in central auditory system metabolic activity associated with congenital deafness may be minimized by prompt auditory habilitation.

Auditory deprivation of the central auditory system resulting from selective inner hair cell loss: animal model of auditory neuropathy.

Auditory neuropathy is often characterized by normal thresholds, present otoacoustic emissions, poor speech discrimination, absent acoustic reflexes, absent or abnormal auditory brainstem response waveform, but normal late cortical potential. This paper describes an animal model that has many characteristics of auditory neuropathy. Chinchillas can be deprived of a significant portion of the neural inputs to the central auditory system by administering carboplatin, an antineoplastic agent that selectively destroys inner hair cells (IHCs) and type I auditory nerve fibers. Selective IHC loss has no effect on distortion product otoacoustic emissions or the cochlear microphonic potential, implying normal outer hair cell function. However, selective IHC loss causes the amplitude of the compound action potential to decrease in proportion to the degree of IHC loss. However, the threshold of the CAP shows little increase with mild to moderate IHC loss. Acoustically responsive auditory nerve fibers in ears with mild to moderate IHC loss have normal thresholds and tuning curves with narrowly tuned tips. Although the central auditory pathway is deprived of much of its sensory inputs, the amplitude of the local field potential in the auditory cortex was normal or enhanced, while those from the inferior colliculus were slightly reduced. The results are related to those of a patient with auditory neuropathy.

Dichotic speech tests.

When central auditory dysfunction is present, ability to understand speech in difficult listening situations can be affected. To study this phenomenon, dichotic speech tests were performed with test material in the Swedish language. Digits, spondees, sentences and consonant-vowel syllables were used as stimuli and the reporting was free or directed. The test material was recorded on CD. The study includes a normal group of 30 people in three different age categories; 11 years, 23-27 years and 67-70 years. It also includes two different groups of subjects with suspected central auditory lesions; 11 children with reading and writing difficulties and 4 adults earlier exposed to organic solvents. The results from the normal group do not show any differences in performance due to age. The children with reading and writing difficulties show a significant deviation for one test with digits and one test with syllables. Three of the four adults exposed to solvents show a significant deviation from the normal group.