Audiometric Changes Research Articles

Phase I and pharmacokinetic study of the novel chemoprotector BNP7787 in combination with cisplatin and attempt to eliminate the hydration schedule

BNP7787 (disodium 2,2′-dithio-bis-ethane sulphonate; Tavocept™) is a novel agent developed to protect against cisplatin (cis-diammine-dichloroplatinum(II))-associated chronic toxicities. In this study, we determined the recommended dose of BNP7787 when preceding a fixed dose of cisplatin, the pharmacokinetics (PKs) and the possible reduction of saline hydration. Patients with advanced solid tumours received BNP7787 in escalating doses of 4.1–41 g m−2 as a 15-min intravenous (i.v.) infusion followed by cisplatin 75 mg m−2 as a 60-min i.v. infusion together with pre- and postcisplatin saline hydration in a volume of 2200 ml; cycles were repeated every 3 weeks. PK was carried out using BNP7787, cisplatin and the combination. Twenty-five patients were enrolled in stage I of the study to determine the recommended dose of BNP7787. No dose-limiting toxicity was reached. The highest dose level of 41 g m−2 resulted in a low incidence of grade 2 toxicities, being nausea and vomiting, dry mouth or bad taste and i.v. injection site discomfort. Doses of BNP7787 ⩾18.4 g m−2 did not show a drug interaction between BNP7787 and cisplatin. In stage II of the study, patients received a fixed dose of BNP7787 of 18.4 g m−2 preceding cisplatin and were entered in prespecified reduced saline hydration steps. A total of 21 patients in cohorts of six to nine patients received reduced saline hydration of 1600 ml (step A), 1000 ml (step B) and 500 ml (step C). In step C, two out of six evaluable patients experienced grade 1 nephrotoxicity. Cisplatin acute toxicities in all 46 patients were as expected. Only five patients complained of paresthesias grade 1 and six developed slight audiometric changes. Partial tumour response was observed in four patients and stable disease in 15 patients. In conclusion, BNP7787 was tolerated well up to doses of 41 g m−2. The recommended dose of 18.4 g m−2 enabled safe reduction of the saline hydration schedule for cisplatin to 1000 ml. Further studies will assess whether BNP7787 offers protection against platinum-related late side effects.

Effects of impulse noise on transiently evoked otoacoustic emission in soldiersEfectos del ruido impulsivo sobre las emisiones otoacústicas evocadas por transitorios en soldados

The aim of the study was to assess the effects of exposure to impulse noise on TEOAE, as compared to PTA. The study comprised 92 soldiers, subjected to impulse noise during military service. The control group consisted of secondary school students, not exposed to noise. Extended high frequency PTA, and TEOAE were recorded before and after one year of military service. The total level of noise and spectrum analysis were performed for all kinds of weapons, separately.The highest levels of noise for weapons were related to frequencies from 1.6–16 kHz. After military service significant deterioration of hearing was observed on average by 6 dB exclusively at the frequencies of 10 and 12 kHz. TEOAE reduction was registered predominantly at frequencies of 2, 3 and 4 kHz, with the greatest decrease at 2 kHz (p<0.02). The control group did not show any significant audiometric changes as well as TEOAE during the time of experiment.

High-dose Cisplatin with amifostine: ototoxicity and pharmacokinetics.

Ototoxicity is a common side effect of high-dose cisplatin treatment. Thiol-containing chemoprotectors ameliorate cisplatin ototoxicity under experimental conditions. The trial was initiated to test the efficacy of amifostine protection in high-dose cisplatin treatment (125-150 mg/m) for metastatic malignant melanoma, to correlate the ototoxic outcome with cisplatin pharmacokinetics, and to evaluate the importance of using a selective analytical method for the quantification of cisplatin. Prospective study of 15 patients with stage IV malignant melanoma. Clinical follow-up of therapeutic response, pure-tone audiometry, and analysis of cisplatin and its monohydrated complex in blood ultrafiltrate by liquid chromatography with postcolumn derivatization were performed. Ultrafiltered blood platinum was analyzed by inductively coupled plasma mass spectrometry. Ototoxicity and gastrointestinal toxicity were the most prominent side effects. Three patients ultimately required hearing aids. All patients had audiometric changes at one or more frequencies after the second treatment course, and all but one patient reported auditory symptoms. No correlation was found between hearing loss and blood cisplatin pharmacokinetics. Platinum levels determined by inductively coupled plasma mass spectrometry were higher than total platinum levels calculated from cisplatin and monohydrated complex concentrations obtained by liquid chromatography analysis. Ototoxicity was unacceptable despite amifostine treatment. Cisplatin pharmacokinetics during the first treatment course were not predictive of hearing loss. Amifostine caused a lowering of dose-normalized area under the concentration-time curve for cisplatin and monohydrated complex. Use of the unselective inductively coupled plasma mass spectrometry analysis leads to an overestimation of active drug. Selective analysis of cisplatin is especially important when evaluating cisplatin pharmacokinetics during chemoprotector treatment.

The status of the contralateral ear in established unilateral Menière's disease.

To determine the incidence of measurable audiometric changes in the contralateral ear and clinical bilateral Menière's disease in individuals with longstanding established unilateral Menière's disease. Analysis of data in an ongoing prospective study. One hundred and one patients who were treated with intratympanic gentamicin installation for disabling unilateral Menière's disease were followed up for a minimum of 2 years. The mean follow-up time between the initial diagnosis to the last audiogram conducted was 12 +/- 7 (range 2-45) years, and the mean follow-up between the first and last audiograms conducted in our clinic was 5 +/- 3 (range 2-15) years. The incidence of Menière's disease (clinical diagnosis) as compared with audiometric changes in the contralateral ear was analyzed. Compared with several published reports, the development of bilateral Menière's disease in our series within the described observation period was much lower (5%). The incidence of contralateral isolated hearing loss in the low frequencies was 16% (average threshold of .25 and .5 kHz of 25 dB or more). The time interval between the initial diagnosis and the onset of contralateral findings ranged from 0 to 26 years. In our experience, individuals with disabling longstanding unilateral disease are not likely to develop bilateral disease. However, a small but significant percentage of patients have audiometric changes in the low frequencies of the contralateral ear (.25, .5 kHz).

Avaliação do perfil auditivo de militares de um quartel do Exército Brasileiro

No serviço militar, os sujeitos estão expostos a ruídos contínuos em oficinas e a ruídos de impacto provenientes de armas de fogo e detonações. Estes ruídos indesejáveis são capazes de causar lesão ao sistema auditivo, muitas vezes irreversível, além de outros efeitos em todo o organismo. OBJETIVO: Avaliar os perfis auditivos de um grupo de militares e, em face dos resultados, incentivar a implementação de medidas preventivas para perdas auditivas, como programa de conservação auditiva. FORMA DE ESTUDO: Coorte transversal. MATERIAL E MÉTODO: Avaliação auditiva de 97 sujeitos que trabalham em uma organização militar do Exército, por meio de entrevista, otoscopia e exames audiométricos. RESULTADOS: 38,1% dos militares examinados apresentaram alterações audiométricas supostamente induzidas por ruído, predominantemente nos artilheiros, com predomínio da perda auditiva unilateral. 64,5% dos militares examinados não utilizava proteção adequada. CONCLUSÃO: A grande ocorrência da perda auditiva entre os militares e a falta de proteção adequada à exposição ao ruído indica a necessidade de se implantarem, nesta categoria, medidas de prevenção de perda auditiva.

Clinical, experimental, and theoretical investigations of the effect of superior semicircular canal dehiscence on hearing mechanisms.

A superior semicircular canal dehiscence affects hearing by introducing a third window into the inner ear that 1) lowers cochlear input impedance, 2) shunts air-conducted sound away from the cochlea resulting in conductive hearing loss, and 3) improves bone-conduction thresholds by increasing the difference in impedance between the vestibule and the round window. Superior semicircular canal dehiscence has been linked to a "conductive" hearing loss characterized by a decrease in the sensitivity to air-conducted sound and hypersensitivity to bone-conducted sound. Four investigations were performed: 1) laser-Doppler vibrometer measurements of sound-induced umbo velocity in patients with computed tomographic scan-confirmed superior semicircular canal dehiscence; 2) laser-Doppler vibrometry of sound-induced motions of the vestibular lymph (either perilymph or endolymph) exposed in a chinchilla model of superior semicircular canal dehiscence; 3) studies in chinchillas of the effect of superior semicircular canal dehiscence on the cochlea's sensitivity to bone-conducted sounds; and 4) anatomically based theoretical analyses of sound flow through the human cochlea and semicircular canals. The low-frequency umbo velocity in superior semicircular canal dehiscence patients without previous middle ear surgery ranged from normal through high normal. This tendency toward hypermobility suggests a decrease in cochlear impedance. Measurements of sound-induced velocity of the lymph within a superior semicircular canal dehiscence in chinchillas demonstrated sound flow through the dehiscence. Measurements of the cochlear potential demonstrated a superior semicircular canal dehiscence-induced increase in response to bone-conducted sound in eight of nine chinchillas. An anatomically based model of the human ear predicts changes in auditory sensitivity similar to audiometric changes in superior semicircular canal dehiscence. The results suggest that superior semicircular canal dehiscence can affect hearing function by introducing a third window into the inner ear.

Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether

Animal studies have demonstrated artemisinin brain stem toxicity with auditory centres being especially affected; there has, to date, been no evidence of such toxicity with oral artemisinins in humans. Subjects working at a construction site in Mozambique had audiometric assessments taken on joining and leaving the project. Subjects with uncomplicated malarias received co-artemether (artemether–lumefantrine) ( n=150) while age-, gender-, weight- and race-matched controls ( n=150) neither suffered malaria nor received antimalarial therapy. Hearing thresholds were measured at predefined frequencies in treated subjects and controls. Subjects receiving co-artemether had a significantly greater heating loss than controls at all frequencies except 250 Hz and 500 Hz ( P values ranging from <0.001 to 0.04, Mann–Whitney U). Mean changes at the different frequencies in subjects ranged from −6.50 dB (95% CI −8.19 to −4.81) [at 1 kHz frequency] to −0.07 dB (95% CI −2.19 to 2.05) [at 6 kHz frequency]. Mean changes in the control group ranged from −4.20 dB (95% CI −5.97 to −2.43) [at 1 kHz frequency] to +2.7dB (95% CI −0.93 to 4.47) [at 6 kHz frequency]. Treatment of uncomplicated malaria with co-artemether is associated with hearing loss, possibly from synergy between potentially ototoxic agents in combination. The safety and neurotoxicity of artemesinins and other endoperoxides needs to be more fully evaluated.

Comment on: Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether

Comment on: Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether

Detecção precoce de ototoxicidade usando emissões otoacústicas produtivas de distorção

Introdução: Os aminoglicosídeos são potencialmente ototóxicos, sendo que a monitorização tradicional detecta ototoxicidade quando a lesão já aconteceu. Objetivo: Estudamos prospectivamente a audição de pacientes que recebiam amicacina, usando audiometria tonal liminar (ATL) e emissões otoacústicas, produtos de distorção (EOA-PD), visando a suspeita precoce de ototoxicidade e sua prevenção. Forma de estudo: Prospectivo randomizado. Material e método: Avaliamos, com ATL, 29 pacientes em tratamento com amicacina, para detectar alterações audiométricas. Desses 29 pacientes, três tiveram alteração na ATL em 6 e/ou 8 kHz (10,34 %) - um com alteração bilateral; os outros dois, unilateral (quatro ouvidos), todos assintomáticos. Realizamos EOA-PD, para estudar a função coclear. Dos 29 pacientes (58 ouvidos), nove (18 ouvidos) foram afastados do estudo por não completarem as testagens das EOA-PD, ficando 20 pacientes (40 ouvidos) para análise. Resultados: Não encontramos alterações significativas nas respostas das EOA-PD durante o vale e o pico sérico da amicacina, como esperado. Quando comparados os ouvidos com e sem alterações audiométricas, as variações das respostas não foram significativas em 1, 2 e 4 kHz; no entanto, em 6 e 8 kHz mostraram diferenças significativas (p&lt;0,05). As respostas das EOA-PD nos ouvidos com ATL normal apresentaram incrementos mais do que quedas; e o contrário aconteceu nos ouvidos que apresentaram ATL alterada, ou seja: houve mais quedas do que incrementos. Conclusões: a ototoxicidade pode ser monitorada eficazmente com EOA-PD durante a administração da droga, independentemente do horário da sua administração; os incrementos nas respostas poderiam ser um sinal precoce de ototoxicidade por aminoglicosídeos.

Low-dose Oral Methotrexate Management of Patients with Bilateral Ménière's Disease

In this retrospective clinical trial, we evaluated the effectiveness of low-dose oral methotrexate in the management of bilateral Ménière's disease of immune-mediated origin. At our tertiary-care referral center, we evaluated ten men and eight women who had longstanding bilateral Ménière's disease that had been unresponsive to traditional conservative medical management. Sixteen of these patients had steroid-responsive bilateral Ménière's disease. Two patients had contraindications to steroids, but their clinical and laboratory evaluations were consistent with an immune-mediated process. Patients were treated with 7.5 to 20 mg/week of oral methotrexate. The mean duration of treatment was 16.7 months (range: 8 to 35), with a mean followup of 2 years (range: 9 mo to 5 yr). Changes in clinical symptoms (vertigo, hearing loss, tinnitus, and aural fullness), audiometric changes, and side effects of therapy were evaluated. Vertigo resolved in 14 patients (78%), was substantially alleviated in three patients (17%), and remained unchanged in one patient (6%). Hearing improved in five patients (28%) and stabilized in seven patients (39%). Tinnitus and aural fullness resolved or was relieved in 11 of 17 (65%) and 13 of 14 (93%) patients, respectively. Side effects were minimal and reversible. We conclude that low-dose oral methotrexate is effective and safe for treating bilateral Ménière's disease of immune-mediated origin. In this study, methotrexate alleviated vertiginous symptoms and improved or stabilized hearing in most patients. Low-dose methotrexate can be considered for patients with immune-mediated bilateral Ménière's disease when long-term treatment is required or when a steroid or cyclophosphamide is contraindicated.

Audiometric changes in patients undergoing hemodialysis and renal transplantation

Audiometric changes in patients undergoing hemodialysis and renal transplantation

Hearing in Patients Operated Unilaterally for Otosclerosis. Self-assessment of Hearing and Audiometric Results

The objective of this study was to examine the outcome of unilateral stapes surgery in one patient group with bilateral hearing loss and one group with unilateral hearing loss. The patients' own estimations of improvement in hearing ability and the occurrence of other ear-related symptoms were examined retrospectively and in a follow-up study. Ninety-five of 123 patients operated for otosclerosis in only one ear between 1987 and 1992 responded to a follow-up examination. Observed audiometric findings and changes thereof, along with the patients' own estimations of their hearing handicap pre- and postoperatively, and the occurrence of other ear-related symptoms were studied. Despite good surgical results (closure of air-bone gap within 20 dB in 94%), 33% of the patients had severe hearing disabilities postoperatively, and many of these patients needed further amplification with a hearing aid. Mild dizziness occurred in 33% of the patients postoperatively and did not decrease over time. Discomfort in the operated ear due to strong sounds was reported in 20%. Change in sound quality occurred in 80% of the operated ears, but tended to disappear over time. From the results of this study it may be concluded that surgery in one ear only, leaving the other ear with poor hearing, is not an optimal hearing rehabilitation of patients with otosclerosis. It is important endevour to achieve bilateral hearing in order to give the patient good social hearing. Postoperative dizziness and unpleasant hearing quality do occur frequently, and the patients need to be informed about these problems preoperatively.

Ototoxic reactions of quinine in healthy persons and patients with Plasmodium falciparum infection

Audiometric changes following quinine administration were studied in healthy Caucasian subjects and patients suffering from falciparum malaria disease. Quinine dihydrochloride was administered intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple doses of 600 mg in 4 h every 8 h in 10 Plasmodium falciparum malaria patients. The hearing function was monitored by conventional and high frequency audiometry. In nine healthy subjects hearing loss was documented at 2–4 h after infusion of Quinine dihydrochloride at a mean maximal plasma quinine concentration of only 2 mg/l. In one healthy subject a persistent loss occurred of 20 dB at 14 kHz in one ear. In all malaria patients severe hearing losses and adverse effects related to ototoxicity were documented, but all the audiograms had returned to normal after 1 week and side effects disappeared. This study has shown that ototoxicity induced by quinine is almost completely reversible in healthy volunteers and in malaria patients.

Electrocochleographic Findings: Meniere's Disease versus Sudden Sensorineural Hearing Loss

Filipo R, Cordier A, Barbara M, Bertoli GA. Electrocochleographic findings: Meniere's disease versus sudden sensorineural hearing loss.Electrocochleography was conducted in 185 patients with Meniere's disease and 117 with sudden deafness. Electrophysiological findings from the two groups were compared in order to identify pathogenic similarities between the two conditions. Parameters investigated were the summating potential (SP)/action potential (AP) ratio, audiometric profiles and audiometric changes after medical therapy. A high SP/AP ratio was found in the patients with sudden deafness, thus supporting a possible hydropic aetiology in this group. In conclusion, electrocochleography can be considered a useful technique as it permits identification of an hydropic condition in certain cases of sudden deafness.

Long-Term Postdural Puncture Auditory Symptoms

To the Editor: Spinal anesthesia is followed by a cerebrospinal fluid leakage around the hole made by the spinal needle. Audiometric disturbances are frequent (found in 42% of patients) [1], whereas hearing loss and tinnitus occur in only 0.3%-8% of patients after spinal anesthesia [2,3]. Since auditory disturbances are related to the same mechanism as postdural puncture headache (PDPH), it would be logical to suggest the use of an epidural blood patch (EBP) in refractory auditory complaints. We thus report one case of long-lasting isolated tinnitus that was dramatically relieved after EBP. A 57-yr-old male presented to an ear, nose, and throat (ENT) surgeon for a history of bilateral tinnitus lasting for 4 years. His symptoms had started 24 h after a diagnostic lumbar puncture that had been ordered for the diagnosis of unexplained depression. Tinnitus was relieved in the supine position only initially, and the patient was obliged to increase the volume of the television and radio, which led to conflict with his spouse. The ENT surgeon sent him to us, after which we performed an EBP with 20 mL of autologous blood. The next day, the patient was symptomless and remained so thereafter. Audiometric testing after spinal anesthesia may reveal hearing loss of 10-40 dB in the low-frequency range, commonly below 1000 Hz. These features are usually transient and disappear within several days [4]. Fog et al. [4] showed that the audiometric changes were more frequent after spinal anesthesia with a 22-gauge Quincke needle (93%) than with a 26-gauge Quincke needle (28.5%). As there are reports of improvement of long-lasting PDPH [5] and short-term auditory symptoms with EBP [6], it was logical to suggest the use of EBP in refractory auditory complaints. Recently, Lybecker and Andersen [7] reported a case of a young woman who underwent three EBPs within 5 wk for recurrent PDPH associated with vestibulocochlear disturbances. In conclusion, thorough questioning regarding a past history of spinal puncture should be undertaken by ENT surgeons, neurologists, and general practitioners whenever the diagnosis of hearing loss or tinnitus remains unclear. EBP should be proposed to confirm the etiology of dural puncture and to relieve auditory symptoms, which may last for years. Patrick Narchi, MD Philippe Veyrac, MD Michel Viale, MD Anesthesia Department and ENT Department Clinique Sainte Croix Le Mans, France Dan Benhamou, MD Department of Anesthesia Hopital Antoine Beclere Clamart, France

The ototoxicity of the cytostatic drug carboplatin in patients with head-neck tumors

The side effects of the anti-cancer drug carboplatin on the cochlea in 65 patients with head and neck cancer were examined in the present study. A possible dependence of ototoxicity on the patient's age, the effect of pre-existing audiometric changes and the carboplatin dose were investigated. A therapy-induced sensory hearing loss was found in 32% of the patients. The average hearing loss was 15 dB and primarily involved the frequency ranges from 4 to 8 kHz. The degree of the hearing defects incurred was not influenced by the patient's age or pre-existing hearing defects but depended on the carboplatin dose used. The severity of carboplatin cochlear ototoxicity was moderate, so that no patient suffered a lack of hearing that was of social significance.

Dose-Related α-Difluoromethylornithine Ototoxicity

We assessed the ototoxicity associated with oral alpha-difluoromethylornithine (DFMO) administration in 58 patients with metastatic malignant melanoma. One hundred seventy-nine sequential audiograms obtained from patients treated with DFMO alone (16 patients) or in combination with alpha 2b-interferon (42 patients) were evaluated. DFMO doses ranged from 2 to 12 g/m2/d and were given over periods of 2 to 50 weeks. Total doses ranging from 60 g/m2 to 1390 g/m2 were correlated with clinical effects and pure tone audiometric changes. By regression analysis cumulative DFMO dose showed a consistent and statistically significant positive relationship to hearing loss at multiple frequencies (500, 1000, 2000, 4000, and 8000 Hz). Patients with normal (threshold less than 30 db) baseline audiograms demonstrated more hearing loss than those with abnormal (threshold greater than or equal to 30 db) baseline audiograms at the higher frequency levels. Of the patients with normal prestudy hearing thresholds 10% or less developed a demonstrable hearing deficit at cumulative DFMO doses below 150 g/m2. Conversely, up to 75% of the patients who received more than 250 g/m2 developed a clinically demonstrable hearing loss. Other factors which adversely affected hearing included age, male gender, and the concomitant use of alpha 2b-interferon. In summary, the risk of clinically significant hearing loss in patients treated with DFMO was primarily related to dose and the presence of a pre-existing hearing deficit.

The Incidence of Aminoglycoside Antibiotic-Induced Hearing Loss

The definition of ototoxicity in most clinical studies of aminoglycoside antibiotics is an increase in pure-tone threshold from a baseline audiogram greater than or equal to 15 dB at two or more frequencies, or greater than or equal to 20 dB at one or more frequencies. In this study, test-retest auditory threshold differences of this magnitude were found in a group of 20 normal volunteers who were not taking any known ototoxic drugs. Depending on which of the two criteria for ototoxicity are used, these data represent a 20% or 33% incidence of ototoxicity. We believe that many of the audiometric changes reported to represent aminoglycoside antibiotic ototoxicity may actually represent the normal test-retest variability of pure-tone audiometry. If this is true, the reported incidence of hearing loss due to aminoglycoside antibiotics may be exaggerated.

Noise-induced hearing loss and orchestral musicians.

Noise-induced hearing loss (NIHL) is well reported among devotees of rock 'n' roll music, but less attention has been focused on players of orchestral music. Sound pressure levels have been recorded from within orchestras during performances, and audiometry has been carried out on orchestral musicians. Short-lasting peaks of sound of high amplitude were found to occur, and some players had audiometric changes consistent with NIHL. However, in practice, there seemed to be no threat to the players' continued livelihood, although the additive effect of presbyacusis in later life poses a potential problem. The difficulties of prevention of NIHL and the attenuation of the high sound levels of orchestras do not seem to be completely soluble.

Bone Conduction Speech Discrimination: An Indication of Cochlear Function in the Immediate Postoperative Period

We illustrate that the apparent sensorineural audiometric changes immediately following stapedectomy are not indicative of a true sensorineural type hearing loss. The cochlear changes evident by postoperative pure-tone and air conduction speech discrimination audiometric tests are not reflective of the true cochlear reserve when the procedure of bone conduction speech discrimination is used. We report 25 consecutive stapedectomy cases in which most of the one-week postoperative audiograms of stapedectomized ears revealed a mid- and high-frequency sensorineural pure-tone loss and a drop in the standard speech discrimination scores. The decrease in speech discrimination, however, was not verified when using the bone-speech discrimination test, using maximum masking in the opposite ear.