Faculty Bibliography

During 1984, six patients have been implanted with a 22-channel cochlear prosthesis. The device features a programmable wearable speech processor using a speech feature encoding strategy. A strict clinical protocol was followed, and no patients have been lost to follow-up. All patients are regular users of the device and have shown a restoration of hearing sensation in response to acoustic stimuli. Pure tone averages ranged from 20 to 47 dB HL and speech detection thresholds varied from 15 to 32.5 dB HL. All patients have shown a recognition of a large variety of environmental sounds, and an improvement in speech recognition ability when the device is used in conjunction with lipreading. Speech reception thresholds using spondee words without lipreading were obtained in three patients at levels of 27.5 to 55 dB HL and one patient had an open-set speech discrimination score (w-22 word list) of 42% without lipreading. In addition, two of the patients show an ability to have limited interactive conversation without the use of lipreading

The decrement of evoked response amplitudes during the presentation of repetitive clicks was examined quantitatively at the level of the eighth nerve and inferior colliculus in mice aged 13-60 days postnatal. The amplitudes of both these potentials were found to decline during the course of stimulation, this being much more severe at the onset of hearing than in adults. Furthermore the following response at the level of the cochlear nerve was adult-like by day 18, while the response at the level of the inferior colliculus continued to improve through day 24. Recordings in the inferior colliculus were consistently obtained in two different regions along the frequency axis. The regions that responded best to a lower range of frequencies (e.g. 3-9 kHz) showed a more rapid and severe decrement in the evoked response to repetitive stimulation than those regions responding best to a higher range of frequencies (e.g. 8-17 kHz). This was found to be the case for repetitive click stimuli and repetitive tone bursts. Single unit responses in the inferior colliculus were consistent with this differential decline as a function of stimulus rate seen along the frequency axis

Neural activity has been implicated as having both a trophic function and a role in synaptic specificity. Sensory deprivation studies in a large number of developing systems have resulted in the pathological morphology of neurons and abnormal response properties. If the relative timing of discharge among afferent terminals is a cue employed by the developing system to refine the array of synaptic connections, then altering the discharge patterns should hinder this process. In the present experiments, we investigate the role played by the temporal pattern of neural activity during the ontogeny of frequency tuning in the mouse central auditory system. Postnatal animals were exposed to acoustic stimuli, repetitive clicks, that continuously entrained a large proportion of primary afferents from the onset of hearing until an age at which tuning curves should have been adult-like. The amount of fatigue to repetitive clicks was characterized at the level of the eighth nerve and inferior colliculus in normal animals. Frequency tuning curves obtained from the inferior colliculus were used as an assay for the specificity of neural connections. Click-reared animals had significantly broader tuning curves than did normally reared mice, particularly for units with best frequencies in the 10- to 15-kHz range. Furthermore, it was found that this change could not be attributed to the selective loss of the sustained component of the response. The affected range is interpreted in terms of the frequency spectrum of the click and the fact that lower frequency regions of the inferior colliculus were found to habituate rapidly. The click-rearing environment did not appear to affect unit spontaneous activity or response latency, nor did it alter the tonotopic map in the inferior colliculus. We argue against the possibility of cochlear damage based on threshold and high frequency cutoff measurements. Mice were reared in a second acoustic environment, repetitive pulses of two added frequencies, as a control for the effects of the click stimulus. This rearing paradigm did not lead to a broadening of tuning curves. It did, however, alter the properties of bimodal tuning curves. For units with bimodal tuning curves having best frequencies in the range of the rearing frequencies, it was found that the second excitatory area had a lower than normal threshold. In addition, the frequency range separating the peaks of the two excitatory regions was statistically smaller. These results are discussed with reference to the specific frequencies used in the rearing paradigm.(ABSTRACT TRUNCATED AT 400 WORDS)

Studies of the effect of surgery on growth failure in adolescents with Crohn's disease have revealed conflicting data. To better determine the role of surgery for growth delay, growth data from 26 patients with Crohn's disease with intestinal resections and/or ileostomies were reviewed, 3 of whom had surgery twice. Operations were performed on 14 Tanner Stage I, 1 Tanner II, 1 Tanner III, and 13 Tanner IV or V patients. In the prepubertal group, 13 of the 14 had growth impairment, only one of whom had surgery primarily for that growth failure. One year after operation, 11 of 13 Tanner I growth failure patients experienced an increase in height velocity of 5.38 +/- 1.18 cm/yr (mean +/- SE;P less than 0.01); 9/11 achieved normal height velocity for Tanner I. Two attained their preillness height percentiles at one year follow-up, while 5 patients attained their preillness height percentiles 2.5 to 10 years following surgery. Of the four who failed to achieve normal height velocity, 3 had early recurrence of active disease. The Tanner Stage II and III patients both had growth failure, and both had a growth spurt following surgery. Of those who were Tanner Stage IV or V at the time of surgery, 5 of 13 had growth failure. Following surgery, none had an increase in height velocity. These data suggest that when patients with Crohn's disease and growth failure are prepubertal and surgery is performed primarily because of failure of medical therapy and/or other complications, a postoperative growth spurt may be expected within one year

The observation that interferon (IFN) therapy causes regression of lesions in some patients with recurrent respiratory papillomatosis (RRP) raises the possibilities that these patients may have abnormalities in endogenous IFN production or in antitumor immune responses stimulated by IFN. We have measured IFN production and natural cytotoxicity (NK activity) in nine patients with RRP, three of whom were receiving exogenous IFN at the time of testing. Production of IFN-gamma induced by the T cell mitogen Staphylococcus enterotoxin A was normal in all patients. Production of IFN-alpha induced by two viruses (Sendai and Newcastle disease viruses) was normal in the six untreated patients, but significantly lower in the patients on IFN therapy. Natural cytotoxicity against K562 target cells, both spontaneous and IFN-stimulated, was normal in all RRP patients tested. Thus, we have shown that the NK-IFN system was intact in untreated patients with RRP. IFN-alpha production in the RRP patients on IFN therapy was low. The significance of these findings is discussed.