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Biomedical subjects

H S Haggerty

Publications and source records attributed to H S Haggerty.

6 recordsLinked to original sources

Neurotrophic factors modulate hair cells and their potassium currents in chick otocyst explants.

Neurotrophins, retinoids and their receptors are present in the sensory epithelia of the inner ear during development. We show that these factors modulate the proliferation of hair cells and their K+-currents when the embryonic day 3 (ED 3) presumptive inner ear (i.e. otocyst) is maintained in organ culture. All trans-retinoic acid (RA) increases hair cell differentiation and enhances the acquisition of outward currents, including a delayed rectifier and a fast activating, transient type, voltage-gated potassium current. In contrast, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) decrease ionic current activity, and the addition of RA with the neurotrophins enhances this inhibitory response in an age-dependent manner. We measured the total number of cells per explant over time to determine precisely when and how these factors inhibit explant growth. We found that high concentrations of BDNF and NT-3 administered together, and low concentrations of both neurotrophins combined and administered with RA suppress otocyst cell numbers after 24 h in vitro. This suppressive response is induced by RA and NT-3, not by RA and BDNF. The suppressive or inhibitory influence of NT-3 and RA is the result of NT-3 binding to the low affinity receptor, p75NTR, not the result of RA increasing mRNA levels for the high affinity receptor, trkC. However, trk may act with p75NTR, as disruption of trk signalling alleviates the inhibitory response induced by NT-3 and RA. Our data suggest that various combinations and/or concentration gradients of these factors can differentially regulate inner ear development and hair cell excitability.

Aging↗

Statistical quantification of 24-hour and monthly variabilities of spontaneous otoacoustic emission frequency in humans.

Previous evidence has suggested a relationship between spontaneous otoacoustic emissions (SOAEs) and established, biological cycles, although detailed statistical quantifications of the suggested relationships do not exist in the literature. In an attempt to statistically quantify the purported circadian and monthly influences on this phenomenon, two experiments were undertaken. The first experiment was conducted over eight weeks, investigating 31 SOAEs recorded from eight women and two men. Time series statistical analysis examined whether daily, weekly, and/or monthly cycles characterized SOAE frequency variability. Results yielded a significant monthly cycle for the majority of SOAEs recorded from the women but for none of the SOAEs recorded from the men. These results suggest the possibility that SOAE frequency fluctuation in women may be entrained to the monthly menstrual cycle. In the second experiment, hourly SOAE frequency stability was examined over a 24-h period to ascertain the nature of the daily frequency variation as precisely as possible. Four SOAEs from two subjects were examined, and time series analysis of these data included (1) modelling the autocorrelation structure of the measurements, (2) resolving each 24-h series of measurements into cyclical components of various periodicities, and (3) testing the statistical significance of given cycles within the spectrum of each series. Findings included a significant 24-h variability of frequency for each SOAE, suggesting the possibility of a circadian influence on frequency fluctuation. Results from the two experiments provide quantitative evidence supporting a hypothetical relationship between SOAEs and established, biological cycles.

Acoustics↗

Clarion cochlear implant: phase I investigational results.

Under phase I of an FDA-approved Investigational Device Exemption (IDE), six patients at the University of California, San Francisco (UCSF) have been implanted with the Clarion, a new multichannel, multiprogrammable cochlear implant system. Over a period of 5 years, the Clarion has been collaboratively developed by UCSF, the Research Triangle Institute (RTI) of North Carolina, and the device manufacturer and sponsor, MiniMed Technologies of Sylmar, California. For UCSF, it represents the culmination of 21 years of cochlear implant research. The Clarion incorporates the 16-contact electrode array developed at UCSF. This electrode is designed with a gentle curve and an elastic memory that allow it to hug the modiolar wall of the scala tympani. In addition, the electrode has mechanical features that prevent it from rotating upward and injuring the basilar membrane. One of the innovations necessary to allow broad clinical application of this device has been the development of an electrode insertion tool to assist the surgeon in safe placement. In each of the six UCSF cases, the insertion tool was used and electrode placement was achieved with ease. With the availability of a variety of speech processing strategies, the Clarion has also provided the opportunity for all of the patients tested to date to achieve some degree of open-set, auditory-only speech recognition. Surgical considerations and preliminary audiologic data demonstrate that the design rationale and objectives of the Clarion have been met.

Aged↗

Alveolar soft part sarcoma of the head and neck. A disease of children and young adults.

Alveolar soft part sarcoma (ASPS) is a rare malignancy of uncertain histologic origin that predominantly afflicts female children and young adults. Forty-three cases occurring in the head and neck have been identified, to which we add a case. The most frequent sites of occurrence in the head and neck are orbit and tongue. Treatment is universally surgical, with limited roles for adjuvant radiotherapy and chemotherapy. Representative populations of patients with orbital, non-orbital and extremity ASPS are compared statistically. Improved disease-free intervals in orbital ASPS vs non-orbital ASPS and head and neck ASPS vs extremity ASPS are documented. Debate exists regarding the histologic origin of ASPS. The additional case presented does not corroborate recent immunohistochemical studies suggesting myogenic origin. Nevertheless, the clinical pattern of disease offers additional support to the myogenic hypothesis of histologic origin.

Adolescent↗

Solving audiometric masking dilemmas with an insert masker.

For some bilateral hearing losses, standard audiometric techniques cannot provide sufficient data for correct otologic diagnosis. These hearing losses are termed "masking dilemmas" because sound attenuation across the head is inadequate to prevent unwanted masking of the test cochlea. In most cases, the masking dilemma can be eliminated by presenting masking through an insert phone in the ear canal, rather than through a standard earphone and cushion. Insert earphones are not standard on most audiometers, but the minimal necessary equipment and alterations are inexpensive, readily available, and require little time to implement. Test time is not increased significantly. Some masking dilemmas will not be solved by the insert masker, but, when properly constructed and used, an insert masker will provide an accurate measurement of cochlear reserve not otherwise obtainable for most cases.

Acoustic Impedance Tests↗

Histological reaction to polyimide films in the cochlea.

The biocompatibility of commercially available polyimides was examined in relation to the sensory and neural structures of the cochlea. Thin films of four different polyimides were prepared as substrates for photolithographically produced scala tympani electrode arrays and implanted in 32 cat cochleae. Following at least three months implantation time, the animals were sacrificed and the cochlea were evaluated histologically for toxicity, differences in the severity of ototoxic effects among the four polyimide groups, and relationships among the different kinds of histopathology secondary to implantation. Findings included the following. Inflammatory reaction to the implants, when present, was generally mild and confined to the immediate vicinity of the implant. Additionally, ototoxic effects were essentially the same across the four groups. Finally, a clear interdependence among the different kinds of cochlear damage secondary to implantation was demonstrated.

Animals↗