Faculty Bibliography

We have investigated the development of dendritic arbors in a central auditory nucleus in the Mongolian gerbil, the lateral superior olive (LSO). The morphology of these arbors has been shown to vary with tonotopic position in adults, with high frequency neurons having a more restricted field. In the present study, qualitative observations were made on horseradish peroxidase-filled neurons from animals 1-11 days postnatal, and quantitative results were obtained from Golgi-impregnated material from animals 10 days postnatal and older. The tonotopic position of each cell was computed as a percent of the total distance along the LSO. The dendritic arbors of high frequency neurons became spatially constrained along the frequency axis during the 3rd postnatal week, while those in the low frequency region retained a broader arborization into adulthood. This refinement was correlated with a decrease in total dendritic length and the number of branch points per neuron, particularly in the high frequency projection region. The distribution of octave bandwidths to which single LSO neurons responded in 13-16 day animals showed a similar course of maturation across the tonotopic axis: high frequency neurons responded to a larger number of octaves, and with greater variability, than those in adults. These data suggest that a specific alteration in dendrite morphology, which occurs after the onset of response to airborne sound, may contribute to adult frequency selectivity

We are interested in the trophic influence of inhibitory synaptic transmission during neuronal maturation. The morphology of dendrites in the gerbil lateral superior olive (LSO) was examined following pharmacological blockade of glycine receptors during postnatal development. The normally occurring change in dendrite morphology during the third postnatal week was prevented. Dendrites had a significantly greater number of branch points, and their arbors were more spread out along the frequency axis in the region of LSO where glycine receptor density is greatest. An identical result has recently been obtained when the glycinergic projection to the LSO was functionally denervated during development. We conclude that glycinergic transmission modulates the maturation of dendrite form during development

Heart rate variation was studied in 56 healthy subjects from ages 20-81 while supine and standing during spontaneous and metronome breathing. Time domain analyses revealed no age effect on supine heart rate but standing heart rate decreased with aging (p less than .008). The SD of R-R intervals decreased with increasing age in both positions (p less than .001). Frequency domain analysis (Fast Fourier Transformation of R-R interval data) showed total spectral content to decrease with aging (p less than .001). Both high frequency (0.20-0.32 Hz) and low frequency (0.04-0.12 Hz) content were reduced with aging (p less than .001). The ratio of high to low frequency content, however, was not affected by age in the supine position nor were changes in this ratio in response to standing during spontaneous breathing. Although the absolute increase in low frequency content upon standing was less with aging (p less than .001), the percent increase in low frequency content was not related to age. Metronome breathing decreased total spectral content (p less than .001) but increased high frequency content, especially in younger subjects (p less than .03). In response to standing, greater proportional and absolute decreases in high frequency content occurred in younger subjects resulting in age differences in the changes in ratios of high to low frequency content with standing during metronome breathing. In summary, decreased heart rate variation was seen with aging, but the balance between parasympathetic and beta-adrenergic input at rest and in response to postural changes does not appear to be influenced by age during spontaneous breathing. Metronome breathing altered spectral content within subjects and produced age-related differences in responses to postural maneuvers not seen during spontaneous breathing.

Composite data describing ocular pharmacokinetics are unreliable because of intersubject variation. To address this problem, an animal model was developed in which multiple aqueous samples from single subjects were obtained. Following direct anterior chamber or intravenous administration of amikacin or chloramphenicol, pharmacokinetic analysis of drug concentrations in the serum and anterior chamber was performed by using a nonlinear least-squares regression program. The number of anterior chamber paracenteses performed did not alter the beta elimination rates or percent penetration into the anterior chamber. The aqueous humor and peripheral-compartment terminal slopes were identical. These data indicate that complete ocular concentration-time curves can be obtained without altering antibiotic pharmacokinetics. Following direct injection into the anterior chamber, the elimination rates for both antibiotics followed a one-compartment model, whereas those following intravenous administration best fit an open, first-order, two-compartment model. Following intravenous administration, the anterior chamber elimination rate constants for both drugs were equal to that of the serum and significantly longer than that following direct injection. The elimination rates of both drugs following direct injection were similar. Systemic administration resulted in drug levels in aqueous humor that persisted longer than those following direct injection. Chloramphenicol, a lipophilic compound, gave higher mean concentrations in aqueous humor than did amikacin. Our model provides a new approach which rigorously examines ocular pharmacokinetics and provides data which suggest that for selected compounds the parenteral route of administration is preferable.

Reinnervation of paralyzed intralaryngeal muscles by axonal sprouting from adjacent intact muscles (the phenomenon of muscular neurotization) has been observed, but the source is uncertain. The potential for laryngeal reinnervation of the posterior cricoarytenoid muscle (PCA) from contralateral PCA motor nerve sprouting in a rabbit model was investigated. Unilateral PCA denervation was produced by vagotomy. The rabbits were examined for signs of PCA recovery for up to 6 months, using fiberoptic endoscopy, electromyography (EMG), and histology. No return of vocal cord abduction, EMG activity, or any nerve sprouting across the midline from the intact PCA was found. We conclude that there is no significant spontaneous intralaryngeal muscular neurotization to the paralyzed PCA. The clinical ramifications of our data will be discussed.

Recurrent aspiration pneumonia is a potentially lethal problem, and its treatment is controversial. A variety of procedures have been advocated to prevent aspiration. These are reviewed briefly. We have been dissatisfied with established procedures because they usually require external approaches with considerable complexity and potential complications. Therefore, we attempted to obstruct the glottic airway by injecting both vocal cords with Teflon in a series of patients with recurrent aspiration pneumonia secondary to severe neurologic impairments. Since Teflon injection of the vocal cords bilaterally did not reliably prevent aspiration, we cannot recommend it for routine use in the treatment of chronic aspiration.

We have previously described a model for in utero cleft lip repair in rabbits. Cleft lip and alveolus (CL) were created in fetal rabbits at 24 days gestation (term, 31 days). In this study, postnatal maxillary growth was evaluated in three groups of animals: 1) unoperated controls, 2) unrepaired CL, and 2) repaired CL. The animals were killed at 4, 12, and 26 weeks after birth. Direct cephalometry was performed on dry skulls to evaluate premaxillary width, anterior maxillary length and width, and posterior maxillary width. The results of this study indicate that rabbits that undergo an in utero CL procedure, with or without repair, exhibit no significant decrease in maxillary length and width when compared with controls.

Fluid electrolyte solutions based on mixtures of butyronitrile (PrCN) and ethyl chloride (EtCl) with Bu4NPF6 or Bu4NClO4 as electrolyte freeze below -180-degrees-C and provide excellent media for cryogenic electrochemical experiments. A 1:2 mixture of PrCN and EtCl exhibits the best combination of freezing point and ionic conductivity for ultralow temperature electrochemistry. Diffusion coefficients for bis(pentamethylcyclopentadienyl) iron (Cp2*Fe) are measurable by protential step chronoamperometry down to -160-degrees-C using a conventionally sized electrode, but the resistivity of the solvent mixture is such that potential sweep voltammetry benefits from the use of microdisk (10 and 25-mu-m diam Pt) or microband (0.2-mu-m wide Au) electrodes. Voltammetry at a chemically modified electrode down to -170-degrees-C is presented for the case of thin films of poly-[Os(bpy)2(vpy)2][PF6]2.