Audiological and electrophysiological alterations in HIV-infected individuals subjected or not to antiretroviral therapy / Alterações audiológicas e eletrofisiológicas em indivíduos infectados pelo HIV submetidos ou não à terapia antirretroviral

Abstract Introduction: The Human Immunodeficiency Virus (HIV) and infections related to it can affect multiple sites in the hearing system. The use of High Activity Anti-Retroviral Therapy (HAART) can cause side effects such as ototoxicity. Thus, no consistent patterns of hearing impairment in adults with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome have been established, and the problems that affect the hearing system of this population warrant further research. Objectives: This study aimed to compare the audiological and electrophysiological data of Human Immunodeficiency Virus-positive patients with and without Acquired Immune Deficiency Syndrome, who were receiving High Activity Anti-Retroviral Therapy, to healthy individuals. Methods: It was a cross-sectional study conducted with 71 subjects (30-48 years old), divided into groups: Research Group I: 16 Human Immunodeficiency Virus-positive individuals without Acquired Immunodeficiency Syndrome (not receiving antiretroviral treatment); Research Group II: 25 Human Immunodeficiency Virus-positive individuals with Acquired Immunodeficiency Syndrome (receiving antiretroviral treatment); Control Group: 30 healthy subjects. All individuals were tested by pure-tone air conduction thresholds at 0.25-8 kHz, extended high frequencies at 9-20 kHz, electrophysiological tests (Auditory Brainstem Response, Middle Latency Responses, Cognitive Potential). Results: Research Group I and Research Group II had higher hearing thresholds in both conventional and high frequency audiometry when compared to the control group, prolonged latency of waves I, III, V and interpeak I-V in Auditory Brainstem Response and prolonged latency of P300 Cognitive Potential. Regarding Middle Latency Responses, there was a decrease in the amplitude of the Pa wave of Research Group II compared to the Research Group I. Conclusions: Both groups with Human Immunodeficiency Virus had higher hearing thresholds when compared to healthy individuals (group exposed to antiretroviral treatment showed the worst hearing threshold) and seemed to have lower neuroelectric transmission speed along the auditory pathway in the brainstem, subcortical and cortical regions.

Resumo Introdução: O HIV e as infecções relacionadas a ele podem afetar vários locais do sistema auditivo. O uso de terapia antirretroviral altamente ativa pode causar efeitos colaterais, como ototoxicidade. Assim, não foram estabelecidos padrões consistentes de deficiência auditiva em adultos com HIV/Aids e os problemas que afetam o sistema auditivo dessa população justificam pesquisas futuras. Objetivos: Este estudo teve como objetivo comparar os dados audiológicos e eletrofisiológicos de pacientes HIV positivos com e sem Aids que recebiam terapia antirretroviral altamente ativa com os de indivíduos saudáveis. Método: Estudo transversal com 71 indivíduos (30-48 anos), divididos em grupos: Grupo de Pesquisa I: 16 indivíduos HIV-positivos sem Aids (não recebiam tratamento antirretroviral); Grupo de Pesquisa II: 25 indivíduos HIV-positivos com Aids (recebiam tratamento antirretroviral); Grupo Controle: 30 indivíduos saudáveis. Todos os indivíduos foram testados para limiares de condução aérea de tons puros a 0,25-8 kHz, altas frequências de 9-20 kHz, testes eletrofisiológicos (potencial evocado auditivo de tronco encefálico, potencial evocado auditivo de média latência, potencial cognitivo). Resultados: Os grupos de pesquisa I e II apresentaram limiares auditivos mais elevados em audiometria convencional e nas frequências altas quando comparados com o grupo controle, latência prolongada das ondas I, III, V e interpico I-V em resposta auditiva de tronco encefálico e latência prolongada de P300. Em relação às respostas de latência média, houve uma diminuição na amplitude da onda Pa do Grupo de pesquisa II em comparação com o grupo de pesquisa I. Conclusões: Ambos os grupos com HIV apresentaram limiares auditivos mais elevados quando comparados aos indivíduos saudáveis (o grupo exposto ao tratamento antirretroviral apresentou o pior limiar auditivo) e parecem ter menor velocidade de transmissão neuroelétrica ao longo da via auditiva nas regiões do tronco encefálico, subcortical e cortical.

Amplitude das emissões otoacústicas produto de distorção e o uso de contraceptivos hormonais: estudo preliminar / Amplitude of distortion product otoacoustic emissions and the use of hormonal contraceptives: preliminary study

OBJETIVO: Identificar se há diferença na amplitude das emissões otoacústicas de mulheres que utilizam e que não utilizam contraceptivo hormonal. MÉTODOS: Participaram da pesquisa 30 mulheres, sendo 15 que utilizam o método contraceptivo hormonal e 15 que não o utilizam, todos sem queixa auditiva e com audição dentro dos padrões de normalidade. A coleta de dados foi realizada por meio das emissões otoacústicas transientes e pelas emissões otoacústicas produto de distorção. RESULTADOS: Não houve diferença entre os valores de amplitude das emissões otoacústicas produto de distorção para as frequências de 1 kHz, 1,4 kHz, 2,8 kHz, 4 kHz e 6 kHz, na orelha direita, nos grupos estudados. Na frequência de 2 kHz houve tendência à diferença entre os valores de amplitude das emissões otoacústicas produto de distorção, comparando-se o grupo de mulheres que não usam contraceptivo hormonal e o grupo das que usam. Na orelha esquerda, não houve diferença entre os valores de amplitude das emissões otoacústicas produto de distorção para as frequências de 1 kHz, 1,4 kHz, 2 kHz, 2,8 kHz, 4 kHz e 6 kHz, nos dois grupos analisados. CONCLUSÃO: Não foram observadas diferenças na amplitude das emissões otoacústicas produto de distorção pelo uso de contraceptivo hormonal, nos grupos estudados.

PURPOSE: To verify differences of otoacoustic emissions responses in women using and not using hormonal contraception. METHODS:Participated in this study 30 female individuals, 15 using a hormonal contraceptive method and 15 that do not use hormonal contraception. All without hearing complaints and hearing within normal limits. Data collection was performed by: transient otoacoustic emissions and distortion product otoacoustic emissions. RESULTS: There was no difference between the amplitude of distortion product otoacoustic emissions for frequencies 1 kHz, 1.4 kHz, 2.8 kHz, 4 kHz and 6 kHz in the right ear between the groups. The frequency of 2 kHz tended to the difference between the amplitude of distortion product otoacoustic emissions between the group of women not using hormonal contraception and use. In the left ear there was no difference between the amplitude of distortion product otoacoustic emissions for frequencies 1 kHz, 1.4 kHz, 2 kHz, 2.8 kHz, 4 kHz and 6 kHz between the groups. CONCLUSION: No differences were observed in the amplitude of distortion product otoacoustic emissions by use of hormonal contraceptives.

Efectos de la glicina sobre los trastornos de conducción del nervio auditivo en pacientes diabéticos tipo 2 con otoneuropatía / Effects of glycine on auditory evoked potentials among diabetic patients with auditory pathway neuropathy

Background: Glycine inhibits the formation of advanced glycation end products that may cause central and peripheral neuronal damage, affecting also the auditory nerve. Aim: To evaluate the effect of glycine on auditory nerve conduction and hearing level among patients with type 2 diabetes mellitus and auditory neuropathy. Material and Methods: Twenty grams of oral glycine per day were administered during 6 months to 28 type 2 diabetic patients aged 58 ± 6 years, with auditory pathway neuropathy. Hearing tests and evoked otoacustic potentials were performed regularly. Fifteen diabetic patients aged 49 ± 8 years, without auditory nerve neuropathy did not receive glycine and were followed as a control group. Results: Among patients receiving glycine, a significant improvement in left ear audiometry at 125, 250 and 500 Hz and right ear audiometry at 500 Hz, was observed. Waves I, III and V (p= 0.02) of evoked otoacustic potentials improved significantly in the left ear and wave I in the right ear. Among controls, waves V and III of evoked otoacoustic potentials had a significant impairment in the left ear. Conclusions: There was an improvement in auditory evoked potentials in patients receiving glycine and an impairment in untreated control patients.

Manifestações eletrofisiológicas em adultos com HIV/AIDS submetidos e não-submetidos à terapia anti-retroviral / Electrophysiological manifestations in adults with HIV/AIDS submitted and not submitted to antiretroviral therapy

BACKGROUND: auditory evoked potentials (AEP) assess the neuroelectric activity on the auditory pathway -from the auditory nerve to the cerebral cortex - in response to an acoustic stimulus or event. Studies have demonstrated electrophysiological abnormalities in individuals with HIV/AIDS. AIM: to characterize the hearing electrophysiological manifestations in adults with HIV/AIDS by comparing the results obtained in the group exposed to antiretroviral therapy with those obtained in the group not exposed to such treatment. METHOD: electrophysiological evaluation of hearing (Auditory Brainstem Response - ABR, Auditory Middle Latency Reponse - AMLR and P300) was conducted in 56 individuals with HIV/AIDS: 24 participants composed group I (not exposed to antiretroviral treatment) and 32 participants composed group II (exposed to treatment). RESULTS: alterations in every AEP were observed in individuals with HIV/ AIDS, especially in the ABR. Indeed, the group exposed to antiretroviral treatment presented more alterations. CONCLUSION: individuals with HIV/AIDS may present alterations on the central and peripheral auditory nervous system. The group exposed to antiretroviral therapy presents more alterations on the brainstem auditory pathway.

TEMA: os potenciais evocados auditivos (PEA) avaliam a atividade neuroelétrica na via auditiva, desde o nervo auditivo até o córtex cerebral, em resposta a um estímulo ou evento acústico. Estudos demonstram anormalidades eletrofisiológicas em indivíduos com HIV/AIDS. OBJETIVO: caracterizar as manifestações eletrofisiológicas da audição em adultos com HIV/AIDS, comparando os resultados obtidos no grupo exposto a tratamento anti-retroviral com os obtidos no grupo não exposto a tratamento. MÉTODO: realizada avaliação eletrofisiológica da audição (PEATE, PEAML e P300) em 56 indivíduos portadores do HIV/AIDS, sendo 24 do Grupo I (não expostos ao tratamento anti-retroviral) e 32 do Grupo II (expostos ao tratamento). RESULTADOS: foram encontradas alterações em todos os PEA nos indivíduos com HIV/AIDS, principalmente no PEATE; sendo que neste, o grupo exposto ao tratamento antiretroviral apresentou mais alterações. CONCLUSÃO: indivíduos com HIV/AIDS podem apresentar alterações no sistema nervoso auditivo periférico e central, sendo que o grupo exposto a tratamento anti-retroviral apresenta mais alterações na via auditiva em tronco encefálico.

Effect of ramipril therapy on cognitive functions in cases of mild to moderate essential hypertension.

Several studies have questioned the effect of hypertension on cognitive functions. Event related potentials (P300) have been used as a reliable and reproducible indicator of cognitive functions. In this non-randomized, open label study we investigated cognitive functions using event related potentials in newly diagnosed mild to moderate essential hypertensive patients and whether or not there was any effect of antihypertensive treatment with angiotensin converting enzyme inhibitor ramipril on the event related potentials. We selected twenty male patients of newly diagnosed mild to moderate essential hypertension by using ambulatory blood pressure monitoring who were previously untreated and compared their event related potentials with 10 normotensive controls. At the beginning of the study, the hypertensive group showed increased P300 and N2 wave latency as compared to the normotensive control subjects. After three months of Ramipril therapy at a dose of 5mg per day, there was a significant decrease in all the ambulatory blood pressure parameters and the mean P300 latency from the pretreatment values. But no significant change in the N2 latency was observed. Thus, treatment with Ramipril 5 mg daily for a period of three months can reverse some aspects of cognitive dysfunction associated with hypertension.

A comparison of the protective effects of systemic administration of a pro-glutathione drug and a Src-PTK inhibitor against noise-induced hearing loss.

Both the antioxidant, n-l-acetyl cysteine (L-NAC) and the Src inhibitor, KX1-004, have been used to protect the cochlea from hazardous noise. To date, KX1-004 has only been used locally on the round window. In the current study, the two drugs were administered systemically. LNAC was delivered intraperitoneally at a dose of 325 mg/kg while KX1-004 was administered subcutaneously at a dose of 50 mg/kg. The noise exposure consisted of a 4 kHz octave band of noise at 100 dB SPL for 6 hours/day for 4 days. The drugs were administered once each day, 30 minutes prior to the onset of the noise exposure. The animals' hearing was estimated using the evoked response records from surgically-implanted chronic electrodes in the inferior colliculi. Animals treated with LNAC and KX1-004 had from 10 to 20 dB less temporary threshold shift at day 1 and an average 10 dB less permanent threshold shift by day 21 when compared to control saline treated animals. There were no significant side effects (i.e.: appetite loss, weight loss, lethargy, etc.) related to either of the drug treatments. KX1-004 produced at least as much protection as L-NAC, but at a significantly lower concentration.

Otoproteção da amifostina aos efeitos ototóxicos da cisplatina: estudo em cobaias albinas por emissões otoacústicas produtos de distorção e microscopia eletrônica de varredura

A Cisplatina é uma potente droga antineoplásica, largamente utilizada para o tratamento do câncer, tanto em adultos quanto em crianças. Dentre seus efeitos colaterais, a ototoxicidade se apresenta como um dos mais importantes e leva à perda auditiva irreversível, bilateral, para as altas freqüências (4KHz -8KHz). Estudos têm tentado identificar drogas que, associadas à cisplatina, possam atuar como otoprotetores. Sabe-se que o mecanismo da ototoxicidade pela cisplatina está relacionado a alterações nos mecanismos antioxidantes das células ciliadas, principalmente as células ciliadas externas da cóclea. A amifostina tem conhecida ação antioxidante, com conhecido efeito otoprotetor aos efeitos lesivos da radioterapia. OBJETIVO: Nossa proposta foi avaliar através de emissões otoacústicas, por produtos de distorção (EOAPD) e por microscopia eletrônica de varredura (MEV), a existência de possível efeito otoprotetor da amifostina no tratamento com cisplatina. FORMA DE ESTUDO: Experimental. MATERIAL E MÉTODO: O estudo foi realizado em cobaias albinas, que foram divididas em três grupos: Grupo 1: 6 animais -12 orelhas - cisplatina 8,0 mg/Kg/dia (via intraperitoneal) por três dias; Grupo 2: 6 animais - 12 orelhas - amifostina 100 mg/Kg/ dia (via intraperitoneal) e 90 minutos após, cisplatina 8,0 mg/Kg/dia (via intraperitoneal) por três dias; Grupo 3: 03 animais - 06 orelhas - amifostina 100 mg/Kg/dia (via intraperitoneal) por três dias. RESULTADO: Encontramos EOAPD presentes e células ciliadas externas presentes, sem lesão anatômica a MEV, nos grupos 2 e 3. Concluímos que a amifostina, por sua ação antioxidante, atua como otoprotetor a ototoxicidade pela cisplatina. No entanto, seu uso não é recomendável nos casos de tumores potencialmente curáveis, por não se saber exatamente a influência da cisplatina na eficácia da quimioterapia.

Critical period for styrene ototoxicity in the rat.

The current experiments were undertaken to determine whether or not styrene-induced hearing loss in the rat depends more on the existence of a critical period between 14 and 21 weeks of age than on body weight. For these purposes, two experiments were carried out with mature Long-Evans rats. In the first experiment, two groups of 5-month old rats, but having different body weight (slim: 314 g vs. fat: 415 g) were exposed to 700 ppm styrene for 4 consecutive weeks, 5 days per week, 6 hours per day. In the second experiment, two groups of rats having the same weight: 345 g, but different ages (14- vs. 21- week old) were exposed to styrene in strictly identical experimental conditions. Auditory sensitivity was tested by recording evoked potentials from the inferior colliculus. Surface preparations of the organ of Corti were also performed to complete the investigation. At the end of the six week recovery period following the styrene exposure, a 7 dB permanent threshold shift (PTS) was obtained with the same age animals regardless of the body weight. Consequently, weight was not a major factor in styrene-induced hearing loss. Age was a more critical factor in determining higher sensitivity to styrene. Indeed, the three months old group had 23.5 dB PTS, whereas the five months old group had only a 7.7 dB PTS at 16 kHz. Thus, a 15 dB difference of PTS was obtained between the rats having the same weight but different age. While the weight does not play a major role in styrene ototoxicity, there is a critical period whose duration lasts more than three months and for which the susceptibility to styrene is enhanced.

Effects of iron therapy on cognition in anemic school going boys.

The present study was conducted on 18 anemic and 34 control subjects (mean age 9.26 +/- 0.26 years) to observe the effect of anemia on cognition and to see effect of 3 months of iron therapy on it. Anemia was defined on the basis of hematological values and peripheral smear examinations. Cognitive data consisted of the recording of the P300 wave of Auditory Event Related Potentials (AERP), Ravens Progressive Matrices Test (RPMT), and Digit Span Attention Test (DSAT) under standard test conditions. RPMT scores were then converted to the intelligence quotient (IQ) scores for comparison. Both anemic and control boys were dewormed after recording pretreatment values and then anemic boys were given iron therapy for 3 months, after which the recordings were taken again. Pretreatment, anemic boys showed significantly lower hematological values, delayed P300 latency, and lower RPMT scores as compared to controls. Post therapy the hematological profile of anemic boys though significantly improved as compared to the pretreatment values, was still significantly lower than that of control boys. The P300 latency values of anemic boys showed improvement but were still significantly delayed than the control group. RPMT values and derived IQ scores of anemic boys were similar to control boys after therapy suggesting that though the 3 months iron therapy regime resulted in improvement in psychometric cognitive tests in anemic boys, the basic P300 defects persisted. This suggests that the P300 component of AERP in anemic children is relatively refractory to 3 months of iron therapy.

P300 in newly diagnosed non-dementing Parkinson's disease: effect of dopaminergic drugs.

Changes in cognitive function are an integral part of the clinical presentation of Parkinson's Disease (PD). P300 potential studies in early stages of Parkinson's disease are lacking and effect of L-dopa therapy on these potentials is controversial. In this study, changes in P300 potentials in early stages of PD and effects of dopaminergic therapy were investigated. P300 waves were elicited by standard auditory 'odd ball' paradigm and were recorded before the start of therapy and 15 days, 3 and 6 months after the start of L-dopa therapy in 25 newly diagnosed patients with idiopathic PD. All patients were classified according to Hoehn and Yahr scale. Minimental status examination (MMSE) was done in all. Control group had 20 normal subjects. The P300 latency was not significantly increased in early Parkinson's disease. This latency was reduced with dopaminergic therapy on 15th day, but increased later. Implications of the data are discussed.

Hippocampus and learning. Possible role of histamine receptors

The effect of local adminstration of histamine and its receptor antagonists into the hippocampus on the learning process of an active avoidance response was studied. The task that the animals had to learn consisted in avoiding an electric shock on their feet after a conditioning ultrasonic 40 kHz tone was on. Latency time was defined as the time in serc rats took to avoid or escape the eletric shock: per cent CAR was defined as the cummulative positive responses during learning session. All rats were implanted into the ventral hippocampus with guide cannulae. On the day of the experiment, rats were microinjected through the guide cannulae with 1 mug of saline solution containing 67.5 nmol of ranitidine or pyrilamine alone or in combination with 45 nmol histamine. All groups were subjected to two sessions of learning. Results show that treatment with histamine was effective to block the adquisition of the response, since animals showed a learning curve significantly inferior to that of the controls. Ranitidine treatment was not able to block the histamine effect. Pyrilamine treatment, instead, was effective to block the inhibitory action of histamine on learning. Results suggest that histamine in hippocampus may be exerting a modulatory control on retrieval processes of memory.

Some observations on clinical, cognitive and neurophysiological changes in subjects consuming indigenous alcohol.

Sixty-two subjects in age range of 25-50 years consuming more than 300 ml of alcohol daily, and an equal number of age matched non-alcoholic volunteers serving as control were tested. Their clinical and neurological evaluation, including electrophysiology was carried out. Their cognitive functions were measured using the modified WAIS system. In alcoholics there was a significant impairment of cognition, especially in orientation, attention and immediate recall. Their P300 wave was grossly abnormal as compared with the controls. Other electrophysiological investigations (EEG, NCV, EMG, BAER, VER) were normal. It is concluded that cognition may be grossly impaired in chronic alcoholics, which may not manifest clinically but is observed only after formal testing.

Estudo experimental da açäo da estrogenoterapia sobre os potenciais auditivos evocados do tronco cerebral em cobaias / Experimental study of the estrogen therapy on the auditory evoked potentials in brainstem of guinea-pigs

Dezessete cobaias albinas foram selecionadas para o experimento após obtençäo do PATC dentro do normal. Foi administrado 1,5 mg de estrógenos conjugados por via intramuscular, diariamente por 30 dias. Os resultados demonstram a efetiva açäo do estrógeno sobre o aparelho auditivo, manifestada por elevaçäo dos limiares do PATC em 47% dos animais, sendo que em dois casos, esse aumento foi importante, ao lado da diminuiçäo da média das amplitudes das ondas I, II, III e IV, que falam a favor de uma atividade ototóxica da droga; por outro lado, uma diminuiçäo da média das latências de todas as ondas do PATC sugere uma açäo, a princípio aparadoxal, facilitadora da condutibilidade elétrica das vias acústicas

Efecto de la nalbufina sobre los componentes tempranos y tardios de los potenciales evocados auditivos / Effect of nalbuphine on early and late components of auditory evoked potentials

Se estudia el efecto de la nalbufina sobre la amplitud y latencia de los componentes tempranos y tardíos de los potenciales evocados auditivos, con el objeto de poder establecer su mecanismo de acción electrofisiológico. Se estudiaron 30 pacientes adultos, siguiendo un procedimiento simple ciego y dos paradigmas farmacológicos diferentes con tres condiciones cada uno: 1 Control inicial (C), solución salina isotónica (S) y control final (C'). 2.C, nalbufina (N) y C'. Los potenciales evocados y otras variables clínicas y electrofisiológicas se registraron 5 a 10 minutos después de S y N, y el C' se registró 90 minutos después. La nalbufina disminuyó significativamente la amplitud de los componentes tardíos P150 y P300 (indicadores electrofisiológicos del proceso de atención selectiva), y no afectó los componentes tempranos PI y PV (indicadores electrofisiológicos del proceso de sensación). Se concluye que el efecto de la nalbufina es predominantemente extralemniscal, afectando estructuras ricas en receptores específicos y relacionados con el proceso de atención selectiva, con poco o ningún efecto sobre estructuras lemniscales relacionadas con la etapa de sensación

Açäo de etomidato sobre os potenciais evocados auditivos do tronco cerebral de ratos / Effect of etomidate on the brainstem auditory evoked potentials of rats

A utilizaçäo dos potenciais evocados auditivos durante cirurgias exige o emprego de anestésicos que näo interfiram sobre as suas características como latência, amplitude e configuraçäo. Alguns compostos, como os anestésicos voláteis, modificam as respostas evocadas a um estímulo sonoro, tanto do córtex como do tronco cerebral. Os agentes venosos possuem efeito diverso, em geral interferindo apenas com as respostas corticais. Na pesquisa foram comparados os efeitos do etomidato (5 mg.kg-1) e do pentobarbital sódico (40 mg.kg-1) sobre os potenciais evocados auditivos do tronco cerebral de 27 ratos. Esses animais foram submetidos a duas sessöes sucessivas com intervalo de uma semana, para registro dos potenciais evocados auditivos do tronco cerebral, sob efeito de etomidato e pentobarbital sódico. Foram usados pulsos retangulares de 0,8 ms, por um gerador de dois canais, estímulos de 100 dB-NHL e seqüência de repetiçäo de 10-1s. As respostas foram registradas e analisadas a latência, a amplitude e a configuraçäo das ondas. Observou-se que o etomidato apresenta um efeito näo distingüível do pentobarbital quanto à latência e configuraçäo do traçado. Houve um aumento estatisticamente significante da amplitude das ondas II e V pelo etomidato em relaçäo ao pentobarbital. Esses resultados mostram que o etomidato näo deprime a conduçäo sensitiva do nível do tronco encefálico