Biomedical subjects

Paul Avan

Publications and source records attributed to Paul Avan.

25 records · Page 2Linked to original sources

PubMed2003

Physiopathological significance of distortion-product otoacoustic emissions at 2f1-f2 produced by high- versus low-level stimuli.

Distortion product otoacoustic emissions emitted by the cochlea at 2f1-f2 in response to pairs of pure tones at f1 and f2 (DPOAE) form a class of otoacoustic emissions and as such, are viewed as a reliable tool for screening outer hair cell (OHC) dysfunctions on a pass/fail basis. However, the persistence of residual DPOAEs from impaired cochleae at high stimulus levels has suggested that above 60-70 dB SPL, instead of reflecting "active" cochlear motion, DPOAEs might represent another "passive" modality: they would thus become unsuitable for analyzing cochlear function. The present work reports the consequences on high- vs low-level DPOAEs of three types of cochlear impairments involving OHCs: progressive OHC degeneration of genetic origin in CD1 mice, complete cochlear ischemia in gerbils, and furosemide injection vs ischemia-reperfusion in gerbils. An alternative to the "active-passive" model was used wherein regardless of stimulus level, cubic DPOAEs are produced by N (probably OHC-borne) nonlinear elements driven by input I and modulated by a function F3 of their operating point o; thus, DPOAE proportional to NI3F3(o). When OHCs degenerated, thereby implying a decrease of N, DPOAE levels also decreased regardless of the stimulus level up to 80 dB SPL, in line with the previous formula but at variance with the prediction of the active-passive concept. Instead of affecting N, the other two experiments impaired the efficiency of the cochlear feedback loop as a result of its electrical drive being decreased by strial dysfunction. As it is well accepted that the impaired basilar-membrane motion, although greatly reduced at low levels, tends to catch up with a normal one at higher levels, it was assumed the same was true with I so that DPOAE levels had to be, and indeed were little affected at high levels while plummeting at low levels, without any need for invoking two modalities for DPOAE generation. Finally, comparisons of furosemide vs ischemia effects revealed additional influences on DPOAEs, possibly accounted for by function F3(o). These results lead to the proposal that although high-level DPOAEs are expected to be poor audiometric indicators, they seem well adapted to assessing the functional integrity of nonlinear elements in OHCs, i.e., presumably their mechanoelectrical transduction channels.

Acoustic Stimulation↗

PubMed2003

Medical management of nasal polyposis: a study in a series of 152 consecutive patients.

BACKGROUND: The management of nasal polyps is undoubtedly a controversial subject. The medical treatment remains the undisputed therapeutic mainstay but most of the publications are aimed at the registration of new molecules from the pharmaceutical industry which explains why they are confined to a single agent. DESIGN: The aim of this study is focused on the evaluation of a dual modality on a series of 152 subjects treated according to a standardized protocol combining a short-term administration of prednisolone and the daily intranasal spraying of beclomethasone. RESULTS: Over the follow-up period of one year, this modality proved to be successful in 68.5% of the subjects; only 31.5% had to undergo surgery after its failure. In the former group, after a six months period, the average symptom reduction reached an improvement rate varying from 35 to 80%, according to the symptom type. During the ensuing six months follow-up period, the improvement was maintained. The average utilization of prednisolone and beclomethasone was assessed for each individual patient. CONCLUSION: Management of nasal polyps should be primarily medical. Resorting to surgical procedures should not be envisaged before a six months trial of dual steroid therapy under strict compliance to treatment.

Administration, Intranasal↗

PubMed2002

Patients affected with Fabry disease have an increased incidence of progressive hearing loss and sudden deafness: an investigation of twenty-two hemizygous male patients.

BACKGROUND: Fabry disease (FD, OMIM 301500) is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of alpha-galactosidase A, a lysosomal enzyme. While the progressive systemic deposition of uncleaved glycosphingolipids throughout the body is known to have protean clinical manifestations, few data are available regarding the cochlear involvement. METHODS: We non-invasively investigated cochlear functions in 22 consecutive hemizygous males (age 19-64 years, mean 39) affected with classic FD. Conventional audiometry, tympanometry, ABR audiometry, otoacoustic emissions were performed in all patients, together with medical history record and physical examination as part of an exhaustive baseline evaluation prior to enzyme replacement therapy. RESULTS: A total of 12 patients (54.5%) with classic FD were found to have abnormal audition. Five patients had progressive hearing loss and seven patients (32%) experienced sudden deafness. In addition, a hearing loss on high-tone frequencies was found in 7 out of the 10 remaining patients without clinical impairment, despite their young age at time of examination. The incidence of hearing loss appeared significantly increased in FD patients with kidney failure (P < 0.01) or cerebrovascular lesions (P < 0.01), whereas there was no correlation with left ventricular hypertrophy. In addition, tinnitus aurium was also found in six patients (27%). CONCLUSION: This is the first evidence of a high incidence of both progressive hearing loss and sudden deafness in a cohort of male patients affected with classic Fabry disease. The exact pathophysiologic mechanism(s) of the cochlear involvement deserves further studies.

Journal Article↗

PubMed2002

Magnitudes and phases of human distortion-product otoacoustic emissions at 2f(1)-f(2) against f(2)/f(1): effects of an audiometric notch.

The influence of the frequency ratio f(2)/f(1) of two pure-tone stimuli on the distortion-product otoacoustic emissions (DPOAEs) at 2f(1)-f(2) was assessed in 14 hearing-impaired human ears exhibiting a narrow audiometric notch at 4 kHz, whereas 11 normally hearing ears served as controls. A fixed-f(2) paradigm was used, with f(2) values varying from 2 to 8 kHz in 1-kHz steps. The intensities of the two stimuli were either 60 or 70 dB SPL. The magnitudes and phases of DPOAEs were extracted so that the bandpass filter-like profile of DPOAE magnitude against f(2)/f(1) (f(2)/f(1) magnitude function) could be characterized by the presence and position of its maximum, and DPOAE group delays were derived from the phase gradient of the DPOAE when f(1) varied. The main difference between normal and impaired ears occurred at 4 kHz in that, in contrast with normal ears, nine impaired ears out of 14 did not present any peak in their f(2)/f(1) magnitude function, while the remaining five ears only differed from normal ones by a slightly shifted maximum toward larger f(2)/f(1)s. Group delays were significantly shortened in all impaired ears, with a tendency to be shorter in the subset of ears with flat DPOAE magnitude profiles with f(2)/f(1). No clear effect of notch depth was observed, and with the chosen stimulus characteristics, no abnormal DPOAE result was observed whenever f(2) fell outside the audiometric notch. It is concluded that DPOAE group delays apparently provide useful objective clues of cochlear dysfunction, more sensitive than DPOAE magnitudes inasmuch as many of them remained near the normal range. Although a majority of f(2)/f(1) magnitude functions were clearly flattened when f(2) was impaired, this feature was less systematic.

Adult↗

PubMed2002

Detection of intracochlear and intracranial pressure changes with otoacoustic emissions: a gerbil model.

Increased intracranial pressure (ICP) is known to affect the phases and levels of lower-frequency distortion-product otoacoustic emissions (DPOAE) in a characteristic manner suggestive of an increase in the stiffness of the stapes system, likely in relation to an attendant increased intracochlear pressure (ICoP). DPOAEs may thus provide an easy non-invasive means of gaining access to the otherwise elusive ICoP. However, the mechanisms by which DPOAEs actually relate to ICoP are unclear and may involve changes in the stiffness of the annular ligament, stapedius muscle and even some indirect contributions of other parts of the middle ear such as the tensor tympani. A systematic study of the role of each middle-ear element on ICoP-to-DPOAE relationships as a function of frequency was undertaken in gerbils under direct control of ICP via an intracranial catheter (from 0 to 500 daPa). After the bulla was widely opened, the tendons of the stapedius and tensor tympani muscles were severed in turn. A standard electroacoustic analog model of the middle ear was used for predicting the forward and reverse middle-ear transfer-functions changes under different experimental manipulations and their consequences on DPOAEs. The observed DPOAE changes chiefly consisted in a phase-lead peaking around 2.15 kHz in closed-bulla, and 1.2 kHz in open-bulla conditions. It was proportional to ICP increase provided ICP exceeded a threshold of about 50 daPa. The profiles of DPOAE shifts matched those derived from the premise that ICoP mainly induced a change in the stiffness of the stapes system. The possible involvement of the stapedius muscle was ruled out by the absence of any effect of cutting its tendon so that the intrinsically non-linear stiffness of the annular ligament must have been the main factor. A relatively minor contribution from the tensor tympani was observed, possibly in relation to the detection of ICoP-induced displacement of the ossicular chain by neuromuscular spindles.

Animals↗

PubMed2002

Ototoxic effects of cisplatin in a Sprague-Dawley rat animal model as revealed by ABR and transiently evoked otoacoustic emission measurements.

The ototoxic effects of cisplatin in a Sprague-Dawley rat model were evaluated by recordings of auditory brainstem responses (ABR) and transiently evoked otoacoustic emissions (TEOAEs). The ABR responses were evoked from alternating clicks and 8, 10, 12, 16, 20 and 30 kHz tone pips in a range from 40 to 100 dB SPL range. The TEOAEs were recorded with a non-linear protocol, and were evoked by a 63.5 dB SPL click stimulus. Twenty five male Sprague-Dawley rats were used in the study, 20 animals were treated with cisplatin (16 mg/kg, body weight) and five animals served as controls. The data showed that 72 h after the cisplatin administration, the TEOAE and ABR variables were significantly altered. The relationship between the ABR and TEOAE variables was shown to be non-linear. The most significant relationships were observed between the TEOAE correlation and the ABR threshold values at 10, 12, and 16 kHz.

Acoustic Stimulation↗

PubMed2001

Correlations among Distortion Product Otoacoustic Emissions, Thresholds and Sensory Cell Impairments.

Distortion product otoacoustic emissions (DPOAE) are increasingly used as an objective test for noninvasive hearing screening. When two pure tones with frequencies f1 and f2 are sent to the cochlea, the most prominent DPOAE is the cubic one produced at 2f1-f2, and this presentation will mainly emphasize its properties. DPOAEs are undoubtedly generated by cochlear nonlinearities. It is widely held that they arise from certain stages of sound processing by the outer hair cells (OHC) and that OHCs ensure normal cochlear sensitivity and tuning. Thus, DPOAEs should provide a privileged tool for monitoring the harmful effects of loud sound because OHCs are known to be one of the main targets of NIHL. Although DPOAEs provide the clinicians with a reliable screening limit of about 30 dB HL around f2, no reliable relationship has been found thus far between possible residual DPOAEs and either hearing loss or amount of impaired sensory cells. Furthermore, puzzling contradictory findings have been reported as to the presence of DPOAEs despite a large hearing loss (i.e. >30-40 dB) notably with high-level stimuli. These observations raise the following issues. What is the generation site of DPOAEs in a normal or pathological cochlea (OHCs, basilar membrane, place tuned to f2, 2f1-f2, places basal to f2.)? Is it necessary to account for interferences between several discrete sources, arising from different locations or different mechanisms and possibly exhibiting differential susceptibility to sensory cell damage? Do DPOAE changes depend on the nature of OHC pathology (NIHL, anoxia, ototoxic drugs, genetics.)? Once a source of DPOAE is characterized, is there any means of modelling the physiological process of its generation and deriving what might quantitatively relate DPOAE amount to sensory cell activity and thresholds? The goal of this presentation is to examine these issues, review the available data and propose a comparatively simple model.

Journal Article↗