Distortion-product otoacoustic emission: early detection in deferoxamine induced ototoxicity.

OBJECTIVE: Deferoxamine therapy in lifelong transfusion-dependent anaemias, as beta-thalassemia major, is associated with an increased risk of ototoxic changes. With increasing survival rates, prevention and/or early detection of ototoxicity are important for providing management options. The predictive value of pure-tone audiometry in early detection of ototoxicity has been questioned, particularly in the higher frequencies. Otoacoustic emissions appear to be more sensitive to cochlear insult than the conventional pure-tone audiometry. The aim of our study was to compare the efficacy of otoacoustic emissions (distortion-product otoacoustic emissions) with that of pure-tone audiometry as method of audiological monitoring. METHODS: Baseline audiometric (0.25-8kHz) and otoacoustic emission testing (distortion-product otoacoustic emissions) was conducted in a group of patients with beta-thalassemia major, 60 of whom met the criteria for inclusion in the study. Comparisons were performed between baseline measurements and those recorded after 20 months. Distortion-product otoacoustic emissions were obtained as DP-grams. The DP-gram amplitude was determined for each child. RESULTS: Threshold changes from baseline were found to be statistically significant from 4 to 8kHz in 68.4% of the subjects (P<0.01). Distortion-product otoacoustic emissions demonstrated a significant threshold shift and a decreased amplitude in the frequencies >3kHz (P<0.05). Furthermore, DP-gram amplitude also reduced significantly at 3kHz (P<0.05) without any similar change in pure-tone audiometry. CONCLUSIONS: As ototoxicity screening tool DP-gram was extremely sensitive and superior to pure-tone audiometry. Their use is recommended for regular monitoring of cochlear function, aiming in prevention of permanent damage.

Tinnitus: pharmacological topodiagnosis.

The difficulty of accurately localizing the source of subjective tinnitus is well-known. Anamnesis and traditional audiological tests can often suggest a source if its origin as peripheral or merely central (or both). Therefore, several authors, such as Risey, Denk, and Shulman, recently proposed identifying the source of subjective tinnitus through the evaluation of the responses reported by patients to adequate pharmacological treatments. Our study presents a useful plan to perform tinnitus topodiagnosis, which consists of specific audiological tests evaluating the characteristics of symptoms (annoyance, pitch, loudness, hyperacusis) and of several pharmacological tests carried out through the administration of particular drugs, the pharmacodynamic mechanisms and meaningful side effects of which are described. On the basis of pharmacological effects on tinnitometry, some drugs will be combined.

Intratympanic dexamethasone treatment for control of subjective idiopathic tinnitus: our clinical experience.

In this report, we summarize our clinical experience with intratympanic dexamethasone treatment (IDT) for control of tinnitus. From March 2000 through February 2001, we observed 54 patients (23 women, 31 men; mean age, 49.6 +/- 7.2 years; range, 24-71 years) suffering from subjective idiopathic tinnitus (SIT). After common audiological tests had been performed; all patients underwent specific topodiagnostic tests to verify the cochlear SIT genesis. The 50 subjects with positive results from a furosemide test and negative results from caraverine and carbamazepine tests were selected for the IDT, consisting of transtympanic perfusion of 4 mg dexamethasone to the round window via the middle ear. The treatment was repeated three times daily for 3 consecutive months. Its short-term effects were evaluated 2 weeks after the last perfusion. In 17 of 50 of these patients (34%), the SIT disappeared; 20 of the 50 (40%) reported a significant decrease of the symptom; and the remaining 13 of the 50 (26%) did not experience any improvement. Therefore, we believe that IDT represents an effective drug delivery system for SIT control, as long as the condition arises from inner ear disorders only and treatment occurs within 3 months of symptom onset.

The role of free radicals and plasmatic antioxidant in Ménière's syndrome.

The objective of this study was verification, through suitable hematochemical tests, of the supposition that central-systemic microtoxicosis plays a role either in the etiopathogenesis of Ménière's syndrome or in labyrinthine pathological processes or hypoacusis. We did not, therefore, exclude other well-known hypotheses in the causality of these pathologies. Nonetheless, one finds, particularly in the Ménière's cases, a constant homogeneous distribution of the metabolic products of this microtoxicosis, such as a high concentration of free radicals and low natural defenses (e.g., antioxidant plasmatic capacity). Therefore, there exists a kind of dangerous central and systemic presence of reactive molecules, aimed toward the polyunsaturated fatty acids and homeostatic complex enzymes, that is not compensated for by the natural antioxidant defense. The presence of this lack of balance, verified by suitable tests, has shown the rationality of use of a product made from reduced glutathione, thioctic acid, cysteine, and other antioxidants as a multipurpose antidote to this element of etiopathogenesis. Patients were divided into three groups (control, conventional therapy, and antioxidant treatment), and those in the antioxidant treatment group, especially those with Ménière's syndrome, demonstrated a net and more significant improvement. Also, parallel clinical and instrument evaluations of this new therapeutic solution, the efficacy of which has already been positively demonstrated, are expected to provide further evidence to support the primary hypothesis.

The use of sodium enoxaparin in the treatment of tinnitus.

Tinnitus is a pathological event caused by abnormal stimulation of any point along the acoustic pathway. Generally, it produces a sharp tone accompanied by hearing impairment. Currently, no widely used standard protocol for treatment of this condition exists, and vascular microthrombotic factors are considered as the main determinants. Prompted by such observations, we implemented a protocol using an anticoagulant, sodium enoxaparin. It is a kind of heparin with a low molecular weight and is endowed with antithrombotic activity. We studied 40 patients (ages 20-65 years) who had been experiencing tinnitus for at least 2 months. We divided patients into two groups: To the first group, enoxaparin was administered for 10 days; the patients in the second group were treated with traditional therapy (corticosteroids, vasoactive agents, multivitamins, and anticoagulants). At the beginning and at the end of the therapy period, the patients were evaluated by instrumental examinations. All patients treated with anticoagulant therapy have shown an evident abatement of their tinnitus symptom. No patient experienced side effects from this treatment. The results indicate that administration of sodium enoxaparin is an excellent mode of therapy for patients with tinnitus.

Origin of sound-evoked EMG responses in human masseter muscles.

Sound is a natural stimulus for both cochlear and saccular receptors. At high intensities it evokes in active masseter muscles of healthy subjects two overlapping reflexes: p11/n15 and p16/n21 waves, whose origin has not yet been demonstrated. Our purpose was to test which receptor in the inner ear is responsible for these reflexes. We compared masseter EMG responses induced in normal subjects (n = 9) by loud clicks (70-100 dB normal hearing level (NHL), 0.1 ms, 3 Hz) to those evoked in subjects with a selective lesion of the cochlea (n = 5), of the vestibule (n = 1) or with mixed cochlear-vestibular failure (n = 5). In controls, 100 dB clicks induced bilaterally, in the unrectified mean EMG (unrEMG), a clear p11 wave followed by a less clear n15 wave and a subsequent n21 wave. Lowering the intensity to 70 dB clicks abolished the p11/n15 wave, while a p16 wave appeared. Rectified mean EMG (rectEMG) showed, at all intensities, an inhibitory deflection corresponding to the p16/n21 wave in the unrEMG. Compared to controls, all deaf subjects had a normal p11 wave, together with more prominent n15 wave; however, the p16/n21 waves, and their corresponding inhibition in the rectEMG, were absent. The vestibular patient had bilaterally clear p11 waves only when 100 dB clicks were delivered bilaterally or to the unaffected ear. Stimulation of the affected ear induced only p16/n21 waves. Data from mixed patients were consistent with those of deaf and vestibular patients. We conclude that click-induced masseter p11/n15 waves are vestibular dependent, while p16/n21 waves depend on cochlear integrity.

A novel autosomal dominant non-syndromic deafness locus (DFNA48) maps to 12q13-q14 in a large Italian family.

Non-syndromic hearing loss is the most common sensory disorder in humans; 15%-20% of cases are transmitted as a dominant trait (NSDA) with 40 loci having been mapped and 16 genes having been identified. Here, we report the mapping of a novel NSDA locus, DFNA48, to chromosome 12q13-q14 in a large multigenerational Italian family. A maximum lod score of 3.31 was obtained with marker D12S83, whereas markers D12S347 and D12S1703 defined a region of approximately 18 cM. Positional candidate genes are being screened for deafness-causing mutations.