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Biomedical subjects

Paul Avan

Publications and source records attributed to Paul Avan.

At least 19 recordsLinked to original sources
PubMed2006

Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse.

The auditory inner hair cell (IHC) ribbon synapse operates with an exceptional temporal precision and maintains a high level of neurotransmitter release. However, the molecular mechanisms underlying IHC synaptic exocytosis are largely unknown. We studied otoferlin, a predicted C2-domain transmembrane protein, which is defective in a recessive form of human deafness. We show that otoferlin expression in the hair cells correlates with afferent synaptogenesis and find that otoferlin localizes to ribbon-associated synaptic vesicles. Otoferlin binds Ca(2+) and displays Ca(2+)-dependent interactions with the SNARE proteins syntaxin1 and SNAP25. Otoferlin deficient mice (Otof(-/-)) are profoundly deaf. Exocytosis in Otof(-/-) IHCs is almost completely abolished, despite normal ribbon synapse morphogenesis and Ca(2+) current. Thus, otoferlin is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca(2+) sensor triggering membrane fusion at the IHC ribbon synapse.

Animals↗
PubMed2006

Mutations in the gene encoding pejvakin, a newly identified protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy.

Auditory neuropathy is a particular type of hearing impairment in which neural transmission of the auditory signal is impaired, while cochlear outer hair cells remain functional. Here we report on DFNB59, a newly identified gene on chromosome 2q31.1-q31.3 mutated in four families segregating autosomal recessive auditory neuropathy. DFNB59 encodes pejvakin, a 352-residue protein. Pejvakin is a paralog of DFNA5, a protein of unknown function also involved in deafness. By immunohistofluorescence, pejvakin is detected in the cell bodies of neurons of the afferent auditory pathway. Furthermore, Dfnb59 knock-in mice, homozygous for the R183W variant identified in one DFNB59 family, show abnormal auditory brainstem responses indicative of neuronal dysfunction along the auditory pathway. Unlike previously described sensorineural deafness genes, all of which underlie cochlear cell pathologies, DFNB59 is the first human gene implicated in nonsyndromic deafness due to a neuronal defect.

Amino Acid Sequence↗
PubMed2006

[Magnetic stimulation of the auditory cortex for disabling tinnitus: preliminary results].

OBJECTIVE: Tinnitus - the perception of sound in one or both ears or in the head when no external sound is present - can be disabling and is especially difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique for activating or inactivating specific areas of the cortex. The aim of this study was to assess the feasibility of magnetic neurostimulation of the primary and secondary auditory cortex in the treatment of disabling chronic tinnitus. PATIENTS AND METHODS: Thirteen patients with tinnitus refractory to several conventional treatments underwent transcranial magnetic stimulation guided by functional magnetic resonance imaging (fMRI). We compared two types of stimulation of targets in the auditory cortex, identified by fMRI: 3-second pulses at high frequency (10 Hz) and 20-minute stimulations at a lower frequency (1 Hz). RESULTS: Brief high-frequency pulses of cortical magnetic stimulation (10 Hz) were not effective. On the other hand, prolonged low frequency (1 Hz) stimulation was effective in 62.5% of patients; the effect appeared 48 h after treatment and lasted for approximately 5 days. DISCUSSION: RTMS may be a new noninvasive technique for studying the cortical plasticity associated with the pathophysiologic mechanisms of chronic tinnitus and may lead to new treatment strategies for patients with disabling tinnitus resistant to all treatment.

Adult↗
PubMed2006

[Tinnitus and cognitive-behavioral therapy: results after 1 year].

INTRODUCTION: Tinnitus is a common auditory symptom that interferes with activities of daily living and is often associated with anxiety and depression. METHOD: This study included consecutive patients with chronic intense tinnitus for more than six months who were treated with Tinnitus Retraining Therapy (TRT), a cognitive-behavioral therapy, after previous treatment failed and after a clinical evaluation based on standardized questionnaires, including the Tinnitus Handicap Questionnaire (THQ). One year after the end of the TRT, the treatment was evaluated by the same standardized questionnaires. RESULTS: This prospective study included 96 consecutive patients (49 women, 47 men, mean age: 48 years). Tinnitus improved significantly in 75%, where significant improvement was defined as a final THQ score of less than 500 after CBT. This improvement varied according to initial THQ scores and was seen in: all patients with moderate (THQ<500), 70.3% of the patients with intermediate (500 1001), and 34.8% of patients with severe (THQ>1000) tinnitus. CONCLUSION: CBT shows promise as a treatment of tinnitus-related distress.

Adult↗
PubMed2006

Influence of allergy on the symptoms and treatment of nasal polyposis.

CONCLUSION: Allergy does not modify the symptoms of nasal polyposis, either initially or after a 1-year medical treatment. OBJECTIVES: To assess the role of allergy in the symptoms and treatment of patients presenting with the diagnosis of nasal polyposis. PATIENTS AND METHODS: Two simultaneous studies were carried out. In the first study, 180 consecutive patients with nasal polyposis (60% males, mean age = 48.4 years) were analyzed to detect whether the severity of their symptoms correlated with the presence of positive allergic tests. In the second study, 74 consecutive patients (57.5% males, mean age = 48.3 years) were analyzed to detect whether the results of a 1-year medical treatment of nasal polyposis were influenced by the presence of positive allergic tests (Phadiatop). Five nasal criteria were scored: nasal obstruction, anterior and posterior rhinorrhea, facial pain, and the loss of sense of smell. The frequency of asthma was evaluated. Treatment of nasal polyposis consisted of washing of the nasal cavities, steroid spray, and oral steroid administration. The amount of steroid consumption (prednisolone and beclomethasone) was studied. RESULTS: In the first study, mean scores of nasal symptoms did not differ between the two groups of patients with and without allergy. The prevalence of asthma (p = 0.03) was higher in the group with than without allergy. In the second study, decrease of all nasal symptoms was not statistically different in the two groups. Cumulative consumption of prednisolone and beclomethasone between baseline and year 1 were similar in the two groups.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Distortion-product otoacoustic emission spectra and high-resolution audiometry in noise-induced hearing loss.

Distortion product otoacoustic emissions (DPOAE) elicited by 60dB SPL pure tones at f1 and f2 were collected at 2f1-f2, in 1/10th octave steps, in a sample of 36 ears from 27 patients with noise-induced hearing loss (NIHL). They were analyzed in the frequency domain against the outcome of high-resolution pure-tone audiometry, performed with the help of a Békésy sweep-frequency automatic audiometer. The characteristics of DPOAE level plots as a function of frequency (the so-called DP-grams), relative to the DPOAE levels of a control age-matched group, were compared to their alleged counterparts on the audiograms, i.e., the lower and upper frequency boundaries of the interval with hearing loss. Ears with NIHL split into two subgroups, one (n = 25) with a notch in the DP-gram such that its lower boundary matched the lower limit of the audiometric notch (linear regression with a slope of 0.91, r(2) = 0.644, p < 0.001). Likewise, when it existed, its upper boundary matched its upper counterpart on the audiogram (linear regression with a slope of 0.96, r(2) = 0.89, p < 0.001). In this respect, DP-grams performed better than transient-evoked OAE spectra, which exhibited poor correlations with audiogram patterns. The second subgroup (n = 11) exhibited normal DPOAEs at all frequencies despite audiometric losses similar to those of the first subgroup. In all cases, DPOAE levels were poor predictors of the degree of hearing losses. It is hypothesized that NIHL in the second subgroup involves inner hair cells or auditory neurons, instead of outer hair cells in the first subgroup. Provided NIHL affected outer hair cells, DP-grams provided a comparatively accurate predictor of the spectral extent of hearing loss.

Adult↗
PubMed2005

Distorted odorant perception: analysis of a series of 56 patients with parosmia.

OBJECTIVE: To characterize the self-reported olfactory and gustatory symptoms, olfactory function, and causes in parosmia. DESIGN: Assessment of olfactory symptoms and function in patients with a chief complaint of parosmia. SETTING: A university hospital clinic and research facility. PATIENTS: Fifty-six consecutive patients presented to the ORL Clinic, European Hospital Georges Pompidou, with a chief complaint of parosmia between October 2001 and November 2003. MAIN OUTCOME MEASURES: Subjective olfactory symptom analysis and olfactory function test results. RESULTS: The mean duration of parosmia was 63.0 months. Forty patients (71.4%) reported associated hyposmia and 16 (28.6%) reported anosmia. Olfactory testing revealed moderate to severe olfactory loss in all patients. Quantitative and qualitative alterations occurred simultaneously in 32 patients (57.1%); parosmia onset occurred within 3 months after quantitative dysosmia in 19 patients (33.9%) and after 3 months in 5 patients (8.9%). The sensation of parosmia was always unpleasant. The main odorant triggers eliciting parosmia are described. The mean severity of flavor dysfunction of the population, evaluated using a 10-cm visual analog scale, was 6.4. Thirty-one patients (55.4%) viewed their olfactory alteration as severely affecting their quality of life. The main clinical association of parosmia was upper respiratory tract infection, found in 42.8% of the patients. Others clinical associations are described. CONCLUSION: The series of patients with parosmia presented herein, the largest in the literature, permits a clinical description of this rare olfactory abnormality.

Adolescent↗
PubMed2005

[Auditory rehabilitation].

Auditory rehabilitation depends of the cause and the severity of the hearing loss (or deafness). Hearing losses dues to middle ear pathologies can beneficiate of medical or surgical treatments, by ossicular prostheses, if it is necessary to restore the function of the ossicles chain. In the sensorineural hearing losses, with inner ear pathology, the use of auditory aid is immediately considered. In the cases for which they are insufficient because of severity of the hearing loss or not suitable because of local non-tolerance, it is possible to use middle ear implant or cochlear implant. The indications of the auditory brainstern implants remain at this day limited to the total bilateral hearing losses due to a complete destruction of cochleae and auditory nerves. These therapeutic orientations are selected after a multidisciplinary evaluation of the deaf person, evaluation that allows the characterization of the hearing loss and its repercussion. In all the cases, the restoration of a bilateral hearing has to be done if possible, making an improvement of the speech comprehension, mainly in the noisy situations, as well as the localization of the sound sources.

Cochlear Implants↗
PubMed2005

Correlation between nasosinusal symptoms and topographic diagnosis in chronic rhinosinusitis.

Rhinitis and sinusitis concern roughly a quarter of the population in the Western world. They are associated with a wide range of symptoms: nasal obstruction, anterior and posterior nasal discharge, sneezing episodes, facial pain or congestion, and taste and smell disorders. The aim of this prospective study was to evaluate the clinical significance of these various symptoms as a function of the topographic diagnosis of chronic rhinosinusitis. The study involved 474 patients with signs of chronic perennial and persistent rhinosinusitis. The disorders of the nasal cavities and paranasal sinuses were classified into three main diagnostic categories: chronic rhinitis, localized sinusitis (mainly, anterior sinusitis), and diffuse rhinosinusitis (ie, nasal polyposis). A principal components analysis was performed. The symptom patterns of the three main clinical entities differed greatly. Most of the following clinical signs--nasal obstruction, anterior and posterior nasal discharge, sneezing, and facial congestion--are found in all diagnostic categories and hold no specific clinical significance. By contrast, four symptoms seem to have a substantial differentiating potential: anosmia and complete loss of flavor for diffuse rhinosinusitis, cacosmia for localized anterior sinusitis, and severe facial pain for localized sinusitis. This study proposes a new analysis of the relationship between symptoms of chronic rhinosinusitis and findings on a sinus computed tomography scan.

Adolescent↗
PubMed2004

[Noninvasive testing of intracranial pressure changes due to body position in infants].

INTRODUCTION: The hydrostatic fluctuations of intracranial pressure are transmitted to the inner ear and then the tension of the anular ligament of the stapes changes. This causes a change of the impedance of the transmission apparatus in the oval window. This in turn can be shown by the measurement of otoacoustic emissions (OAE), since both the stimulus and the emissions travel through the oval window. It has been shown that in adults the phase of otoacoustic emissions changes due to changes in intracranial pressure (eg. during positioning from sitting to head-down (Trendelenburg) position). AIMS: The aim of their study was to examine if these phase changes can be elicited in infants and children. RESULTS: In young infants (between 2 and 4 months old) there was no reproducible phase shift during positioning into Trendelenburg position, in children (between 3 and 4 years old) there was a significantly smaller phase shift than in adults. According to their theory that difference is due to the smaller hydrostatic pressure change and the fact that the skull distents easily thereby compensating for the volume change.

Female↗
PubMed2004

Medial olivocochlear efferent activity in awake guinea pigs.

Cochlear outer hair cells receive numerous connections from the medial olivocochlear efferent neurons. Medial olivocochlear efferent activity is highly dependent on the level of anesthesia. The present study was thus designed to investigate the efficiency of contralateral white noise stimulation on the distortion product otoacoustic emissions (DPOAEs) in a large number of awake guinea pigs, and to compare in the same animals the effect of urethane- and pentobarbitone-anesthesia. The monitoring of DPOAEs during contralateral white noise stimulation in awake animals requires the development of a soft restraining box, together with a conditioning technique for the animals to accept the contralateral sound and DPOAEs monitoring device. This technique allows us to demonstrate that contralateral sound suppression is much stronger in awake than in anesthetized animals. In all the cases, the contralateral sound suppression was abolished 3 h after i.m. injection of gentamicin, an aminoglycoside antibiotic which blocks the medial olivocochlear efferents. These results suggest that future studies have to explore the function of medial olivocochlear efferents in awake animals.

Acoustic Stimulation↗
PubMed2004

Non-specific bronchial hyperresponsiveness is a risk factor for steroid insensitivity in nasal polyposis.

OBJECTIVE: Management of nasal polyposis should be primarily medical. Resorting to intranasal ethmoidectomy should not be envisaged before a trial of dual steroid therapy. Nevertheless, no risk factor for steroid insensitivity in patients with nasal polyposis is actually defined. The aim of this study is to evaluate whether the presence of asthma and/or non-specific bronchial hyperresponsiveness (BHR) can be considered a risk factor for steroid insensitivity. MATERIAL AND METHODS: This study focused on the evaluation of a dual modality, topical and systemic, over a follow-up period of 3 years. A total of 55 subjects with and 45 subjects without BHR were treated according to a standardized therapeutic protocol combining short-term oral administration of prednisolone and a daily intranasal spray of beclomethasone. RESULTS: Over the follow-up period of 3 years, this dual modality proved to be successful in 93.4% of subjects without BHR and without aspirin idiosyncrasy, in 82.2% of subjects with BHR and without aspirin idiosyncrasy and in 60% of subjects with BHR and aspirin idiosyncrasy. The percentage of patients who underwent surgery after the failure of medical treatment was significantly larger in patients with than without BHR (p < 0.05) and in patients with than without aspirin idiosyncrasy (p < 0.02). CONCLUSION: The presence of BHR and/or aspirin idiosyncrasy can be considered a major risk factor for steroid insensitivity in patients with nasal polyposis.

Administration, Oral↗
PubMed2004

Screening of olfactory function using the Biolfa olfactory test: investigations in patients with dysosmia.

OBJECTIVE: To present a statistical evaluation of a new olfactory test, Biolfa. MATERIAL AND METHODS: The olfactory test was carried out in individuals with normal olfactory function (n=67; 31 males; mean age 27.4 years) and in patients with mild, moderate or severe hyposmia (n=155; 61 males; mean age 54.6 years). The main diagnoses of the hyposmic patients were upper respiratory tract infection (32%), nasal polyposis (24%), head trauma (8%), idiopathic (8%), old age (5%) and chronic rhinitis (5%). In the first part of the test, olfactory thresholds were measured for three different substances (eugenol, aldehyde C14 and phenyl ethyl alcohol). The second part comprised an odor identification test for determining olfactory function for a large panel of common odors of Southern European countries. RESULTS: Mean olfactory thresholds were determined for subjects with normal olfaction and hyposmic patients; there was a statistically significant relationship between olfactory thresholds and degree of olfaction (mild to moderate hyposmia versus severe hyposmia). For the odor identification test, a global score was determined to allow the differentiation of normosmic subjects from patients with mild, moderate or severe hyposmia. The principles of decision theory (i.e. analysis of the receiver operating characteristic curve) were applied to the problem of evaluating the ability of Biolfa to distinguish subnormal subjects from hyposmic subjects. CONCLUSION: This study provides a basis for the routine clinical use of Biolfa.

Adult↗
PubMed2004

Frequency specificity of distortion-product otoacoustic emissions produced by high-level tones despite inefficient cochlear electromechanical feedback.

Distortion product otoacoustic emissions (DPOAEs) are thought to stem from the outer hair cells (OHCs) around the normally narrow place tuned to the primary tone stimuli. They are thus said to be frequency-specific: their local absence should accurately pinpoint local OHC damage. Yet the influence of impaired tuning on DPOAE frequency specificity is poorly documented. Mice with local damage to OHCs were examined. Their DPOAEs were frequency-specific in that audiometric notches were accurately tracked. The same cochleae were further impaired by ischemia or furosemide injection inducing strial dysfunction with flat loss of sensitivity and tuning, while the preexisting pattern of damaged OHCs remained unaltered. Despite the loss of cochlear activity, DPOAEs produced by high-level (> or =70 dB SPL) primaries remained large in about the same interval where they had been initially normal, i.e., that with nondamaged OHCs, albeit with a slight frequency shift, of -1.1 kHz on average. Thus, the ability of DPOAEs to map structurally intact OHCs cannot be a mere consequence of cochlear tuning as it largely persists in its absence. The key element for this correct mapping is likely part of intact OHC structures (e.g., stereocilia bundles) and must have some tuning of its own.

Acoustic Stimulation↗
PubMed2004

Medical treatment of stage I nasal polyposis over a 3-year follow-up period.

PURPOSE: To determine the effects of a standardized therapeutic protocol (short-term oral administration of prednisolone and daily intranasal spray of beclometasone) on stage I nasal polyposis over a follow-up period of 3 years. PROCEDURES: Assessments (evaluation of nasal function and drug consumption) were conducted at baseline and every 3 months on 54 consecutive patients with stage I nasal polyposis during 3 years. RESULTS: Over the follow-up period of 3 years, this dual modality proved to be successful in 87% of the subjects; only 13% had to undergo surgery after its failure. The average symptom reduction reached an improvement rate varying from 66 to 94.8%, according to the symptom type. The daily dosage of prednisolone and beclometasone was progressively decreased, while the gain in nasal comfort was being preserved. CONCLUSION: Management of stage I nasal polyps should be primarily medical.

Administration, Intranasal↗
PubMed2003

Effect of click intensity on click-evoked otoacoustic emission waveforms: implications for the origin of emissions.

The rather shallow growth of click-evoked otoacoustic emissions (CEOAE) with click intensity, namely <1 dB/dB, distinguishes genuine CEOAEs from stimulus artifacts, thereby providing the rationale for the popular 'derived nonlinear recording' method. However, other CEOAE nonlinearities regarding phase or envelope dependence on stimulus intensity have been barely acknowledged so far. The present work used CEOAEs from 20 normal ears recorded in response to 50-86 dB peak equivalent SPL clicks. The phases of CEOAE spectral components varied considerably with click intensity (sometimes more than 120 degrees ), mostly in a monotonic manner and in such a way that in the majority of ears, phase lagged with increasing intensity. When present, synchronized spontaneous otoacoustic emissions exhibited the same behavior. In a few instances, conspicuous frequency shifts of CEOAE spectral peaks were seen. In contrast to CEOAE phases, envelopes were almost intensity-invariant. This behavior contrasts with that of basilar membrane motion at the place tuned to the stimulus frequency, as consistently disclosed by several recent publications, i.e., no phase shift and large envelope shift with stimulus intensity. It is thought that the phase invariance of basilar membrane motion implies that whatever they do, outer hair cells cannot alter the resonance frequency of the cochlear partition. If one elaborates along this line of reasoning, the large phase shift of CEOAEs with click intensity implies that CEOAEs at frequency f cannot come from the place tuned to f and that instead, they may be intermodulation distortion products produced by nonlinear interactions between spectral components of the click stimulus over a significant length of the basilar membrane.

Acoustic Stimulation↗
PubMed2003

Corticosteroid treatment in nasal polyposis with a three-year follow-up period.

OBJECTIVES/HYPOTHESIS: The management of nasal polyposis is undoubtedly a controversial subject. The part played by surgery seems to be steadily growing, if the number of published reports dedicated to this approach is any yardstick. Although the medical treatment remains the undisputed therapeutic mainstay, trials dedicated to the long-term assessment of its overall efficacy are scarce. STUDY DESIGN: Retrospective medical record review. METHODS: The aim of the study is focused on the evaluation of a dual modality, topical and systemic, over a follow-up period of 3 years. In all, 100 patients were treated according to a standardized therapeutic protocol combining short-term oral administration of prednisolone and daily intranasal spray of beclomethasone. RESULTS: Over the follow-up period of 3 years, this dual modality proved to be successful in 85% of the patients; only 15% had to undergo surgery after its failure. The average symptom reduction reached an improvement rate varying from 58% to 80%, according to the symptom type. The daily dosage of prednisolone and beclomethasone was progressively decreased while the gain in nasal comfort was being preserved. CONCLUSIONS: Management of nasal polyps should be primarily medical. Resorting to surgical procedures should not be envisaged before a trial is conducted of dual steroid therapy under a regimen of strict compliance to treatment.

Administration, Intranasal↗