Comparison of onset and steady-state responses of hearing aids: implications for use of the auditory brainstem response in the selection of hearing aids

Input-output (I/O) functions of hearing aids were measured in response to a 2000-Hz tone burst, having 0.5 ms rise/fall time and 10 ms duration. I/O functions, measured with a hearing-aid analyzer, served as reference conditions. Hearing-aid outputs at onset and during the steady-state portion of the waveform differed; these differences often depended upon stimulus rate. The relation between onset and steady-state estimates of output were not always predictable from hearing-aid attack and release times. These findings indicate that the steady-state output limitation characteristics of hearing aids cannot be estimated from their onset responses. In turn, this suggests that ABR measurements may not provide accurate estimates of the compressive characteristics of hearing aids.     

Novel insight into the dangerous connection between diabetes and heart failure

Heart failure (HF) affects approximately 1–2?% of the adult population. Diabetes mellitus (DM) is one of the most frequent comorbidities in HF, portending a worse prognosis. DM is associated with an increased risk of artery disease, and consequently of post-ischemic HF, but it may also alter directly the myocardial structure and function. Insights into the pathophysiological mechanisms of diabetic cardiomyopathy have been provided by both experimental and clinical investigations. In recent years, it has emerged that the fibrotic process is a result of the convergence of multiple neurohormonal alterations in diabetic cardiomyopathy at the basis of disease progression and phenotype determination: HF with reduced or preserved ejection fraction. Therapies for HF and DM should demonstrate an improved prognosis and have a neutral effect on glucose homeostasis and the risk of HF development.     

Biological Drugs: Classic Adverse Effects and New Clinical Evidences

The last 20 years was characterized by great improvements in the efficacy and tolerability of anticancer therapies. Most of these changes are related to the introduction of targeted drugs, which presents a better activity on the biology of cancer and less toxicity. Nevertheless, the initial enthusiasm was cooled by the emerging evidences of cardiac side effects. The aim of this review is to describe the actual knowledge about the possible cardiotoxicity of targeted drugs. The most important need is the detection of early cardiotoxicity and the evidence of subtle myocardial dysfunction that allows to begin a protective therapy. In our review we analyzed the non invasive imaging techniques to early predict myocardial dysfunction. Echocardiography seems to be the ideal method for her availability, safety and clinical usefulness, in particular the new echocardiographic techniques like speckle tracking.     

Determining the upper limits of stimulation for auditory steady-state response measurements

OBJECTIVE: To determine the maximum stimulus levels at which a measured auditory steady-state response (ASSR) can be assumed to be a reliable measure of auditory thresholds. DESIGN: ASSR thresholds were measured at octave frequencies from 500 to 4000 Hz in 10 subjects with profound hearing loss. These subjects provided no behavioral responses to sound at the limits of pure-tone audiometers and at the limits of the stimulus levels produced by the ASSR device. Subjects were divided into two groups of five, with repeated measures obtained within the same session in one group and repeated measures obtained in a separate session on a different day in the other group. RESULTS: ASSR thresholds were observed in all 10 subjects at each of four frequencies and in both trials. On average, these ASSR thresholds were observed at 100 dB HL (SD = 5 dB). Because these responses were at least 18 to 22 dB below the limits of the equipment where all subjects had no behavioral responses, it is reasonable to conclude that the ASSRs were not generated by the auditory system. CONCLUSIONS: An artifact or distortion may be present in the recording of ASSRs at high levels. These data bring into question the view that there is a wider dynamic range for ASSR measurements compared with auditory brain stem response measurements, at least with current implementation.     

Identification of neonatal hearing impairment: auditory brain stem responses in the perinatal period

OBJECTIVES: 1) To describe the auditory brain stem response (ABR) measurement system and optimized methods used for study of newborn hearing screening. 2) To determine how recording and infant factors related to the screening, using well-defined, specific ABR outcome measures. DESIGN: Seven thousand one hundred seventy-nine infants, 4478 from the neonatal intensive care unit (NICU) and the remaining from the well-baby nursery, were evaluated with an automated ABR protocol in each ear. Two channel recordings were obtained (vertex to mastoid or channel A and vertex to nape of neck or channel B) in response to click stimuli of 30 and 69 dB nHL in all infants as well as 50 dB nHL in infants who did not meet criteria for response at 30 dB. Criteria for response included F(SP) > or =3.1 and a tester-judgment of response. Criteria could be met in the first or repeat test with a maximum of 6144 accepted sweeps per test. RESULTS: More than 99% of infants could complete the ABR protocol. More than 90% of NICU and well-baby nursery infants "passed" given the strict criteria for response, whereas 86% of those with high risk factors met criterion for ABR response detection. The number of infants who did not meet ABR response criteria in one or both ears was systematically related to stimulus level with the largest group not meeting criteria at 30 dB followed by 50 and 69 dB nHL. Meeting criteria on the ABR was positively correlated with the amplitude of wave V, with low noise and low electrode impedance. Factors that predicted how many sweeps would be needed to reach criterion F(SP) included noise level of the test site, state of the baby (for example, quiet sleep versus crying), recording noise, electrode impedance and response latency. Channel A (vertex to mastoid) reached criterion more often than channel B (vertex to nape of neck) due to higher noise in channel B. Average total test time for 30 dB nHL screening in both ears was under 8 minutes. Well babies with risk factors took slightly longer to evaluate than other groups with this automated ABR procedure and have higher noise levels. CONCLUSIONS: ABR implemented with an automated detection algorithm using a 30 dB nHL click stimulus is reliable technique for rapid assessment of auditory status in newborns. Factors other than hearing loss that influenced the test result include infant state, electrode location and impedance, testing site, and infant risk status. Even so, ABRs were reliably recorded in the vast majority of babies under circumstances in which most babies are found in the perinatal period.     

Application of ABRs to the hearing-aid selection process: preliminary data

This paper describes preliminary data on the use of click-evoked ABRs in the hearing aid selection process. Four normal-hearing and 4 hearing-impaired subjects were tested with a hearing aid set at three different frequency response settings. Estimates of gain were calculated using shifts in Wave V thresholds, shifts in Wave V latency-level functions, acoustic-reflex measurements, coupler gain measurements, and measurements of functional gain. Results suggest that the click-evoked ABR does not distinguish between differing amounts of low-frequency gain, although reasonable estimates of high-frequency gain appear possible. Also discussed are technical factors that must be considered when using the ABR in the hearing aid evaluation process.     

Auditory brain stem responses to high-frequency tone bursts in normal-hearing subjects

ABR and behavioral thresholds and ABR latencies were measured from six normal-hearing subjects in response to tone bursts, having frequencies of 9,000 to 16,000 Hz. In general, ABR thresholds were higher than behavioral thresholds; however, the differences were typically less than those observed for lower frequencies. Wave V latency-intensity functions were less dependent on frequency for these stimuli than they were for lower frequency stimuli. This may be due to the fact that higher frequencies are represented over a very narrow area of the cochlea and that minor variability in the measurement of latencies might obscure small differences in latency as a function of frequency. In general, these data suggest that ABRs can be measured in response to high-frequency stimuli and that these measurements may have clinical utility, especially when monitoring ototoxic effects in difficult-to-test patients.     

Naturally processed and presented epitopes of the islet cell autoantigen IA-2 eluted from HLA-DR4

During immune responses, antigen-presenting cells (APCs) process antigens and present peptide epitopes complexed with human leukocyte antigen (HLA) molecules. CD4 cells recognize these naturally processed and presented epitopes (NPPEs) bound to HLA class II molecules. Epitope identification is important for developing diagnostic and therapeutic tools for immune-mediated diseases and providing insight into their etiology, but current approaches overlook effects of natural processing on epitope selection. We have developed a technique to identify NPPEs using mass spectrometry (MS) after antigen is targeted onto APCs using a lectin-based antigen delivery system (ADS). We applied the technique to identify NPPEs of the intracellular domain of the type 1 diabetes mellitus-associated (type 1 DM-associated) autoantigen insulinoma-associated-2 (IA-2ic), presented by HLA-DR4 (0401). IA-2ic-derived NPPEs eluted from HLA-DR4 constitute 6 sets of peptides nested around distinct core regions. Synthetic peptides based on these regions bind HLA-DR4 and elicit primary T-cell proliferation frequently in HLA-DR4-positive type 1 DM patients, but rarely in non-HLA-DR4 patients, and in none of the HLA-DR4 nondiabetic controls we tested. This flexible, direct approach identifies an HLA allele-specific map of NPPEs for any antigen, presented by any HLA class II molecule. This method should enable a greater understanding of epitope selection and lead to the generation of sensitive and specific reagents for detecting autoreactive T cells.     

Characterization of seven new monoclonal antibodies against human DR, DR + DP and DQ1 + DQ3 antigens

Seven murine monoclonal antibodies were prepared that react with human class II antigens. Four of them (HL-39, MEM-12, MEM-24G, and MEM-32B: react with a monomorphic determinant dependent on association of heavy and light chains of DR antigens, two others (HL-38 and HL-40) recognize a monomorphic determinant localized on the light chains of DR and DP antigens. The antibody HL-37 is directed against a determinant present on DQ1 and DQ3, but not DQ2 molecules; at least in the case of DQ1, the epitope recognized is located on the light chain.