Experimental analyses of the source of ABR wave II

Recent reports based on direct recording from various locations along the auditory nerve in humans during neurosurgical procedures have suggested that the auditory nerve-brainstem response (ABR) wave II is generated by the same neurons which generate wave I. In order to analyze this possibility using a different approach, ABR was recorded in ten rats in response to several click intensities and click repetition rates. These studies were also repeated in ten human volunteers. The amplitudes and latencies of ABR waves I, II and III were analyzed in order to determine if wave I and II behaved in a parallel fashion with changes in stimulus intensity and latency, as would be expected from the physiological "all or none law" if both waves were generated by the same axons. Several types of analyses indicate that the amplitudes of ABR waves I and II do not grow in amplitude in a parallel fashion with increases in stimulus intensity and decreases in stimulus rate. This is evidence either for independent sources of waves I and II or for composite sources of wave II both from the auditory nerve and the cochlear nuclei.     

Vestibular end-organ impairment in an animal model of type 2 diabetes mellitus

OBJECTIVES/HYPOTHESIS: To define and assess the functional impairment of the vestibular part of the inner ear in a diabetic state, using a direct and objective test for evaluating the vestibular end-organ and an animal model for diet-induced type 2 diabetes mellitus. STUDY DESIGN: Prospective controlled animal study. METHODS: Two groups of sand rats (Psammomys obesus) were maintained on two different diets. The experimental group received a specially designed high-energy diet known to induce a diabetic state, and the control group a low-energy diet maintaining these animals in a normal metabolic state. After 1 month of documented hyperglycemia in the experimental group, recordings of vestibular evoked potentials (VsEPs) and recordings of auditory brainstem response (ABR) were conducted in all animals. The latency and the amplitude of the first wave of both responses, shown to reflect end-organ activity, were compared between the two groups. RESULTS: The mean latency of the first wave of the VsEPs was significantly (P = .002) prolonged and the amplitude was significantly (P = .005) decreased in the diabetic group in comparison to the control group. The latency of the first wave of ABR was significantly (P = .02) prolonged, the amplitude was not significantly decreased, and threshold was significantly elevated (P = .01) in the diabetic group. CONCLUSION: For the first time, using an objective assessment test, functional impairment of the vestibular part of the inner ear has been demonstrated in the diabetic metabolic state. Despite this being an animal study, these findings would seem to indicate that the vestibular-end-organ should be added to the long list of organs and tissues adversely affected by diabetes.     

The effect of various durations of noise exposure on auditory brainstem response, distortion product otoacoustic emissions and transient evoked otoacoustic emissions in rats

This study was designed to investigate the effect of various durations of noise exposure in animals on physiological responses from the cochlea which are also used clinically in humans: auditory brainstem response (ABR), transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs). Rats were exposed to 113 dB SPL broad-band noise (12 h on/12 h off) for durations of 3, 6, 9, 12, 15 and 21 days, and tested 24 h after cessation of the noise and again after a period of 6 weeks. ABR threshold to click stimuli and to a 2-kHz tone burst (TB), TEOAE energy content and DPOAE amplitude in the exposed rats were compared to those in a group of control rats not exposed to noise. ABR thresholds (click and TB) were significantly elevated in all exposure duration groups compared to control rats. DPOAE amplitudes and TEOAE energy content were significantly reduced. The mean ABR thresholds following 21 days exposure were significantly greater (click = 100 dB pe SPL; TB = 115 dB pe SPL) than those following 3 days exposure (click = 86 dB pe SPL; TB = 91 dB pe SPL). Linear regression analysis between recorded responses and duration of noise exposure (days) showed a significant increase in ABR thresholds of approximately 0.8-- 1.4 dB/day. TEOAE and DPOAE responses showed no such dependence on noise duration and were already maximally reduced after only 3 days of exposure. This can be explained by the possibility that short noise exposures may cause damage to the early, more active stages of cochlear transduction (as shown by TEOAEs and DPOAEs). As the noise exposure continues, further damage may be induced at additional, later stages of the cochlear transduction cascade (as shown by ABR). Thus, ABR seems more sensitive to noise duration than OAE measures.     

Mechanism and rate of middle ear fluid absorption

Several mechanisms have been suggested to explain the clearance of fluids from the middle ear. These include a pumping action through the eustachian tube, mucociliary beating through the tube, outflow of water to the blood due to osmotic gradients and an active Na(+) transport driving water absorption. In order to assess these mechanisms, the middle ear cavity of paralyzed, ventilated (eustachian tube occluded) guinea pigs was filled with fluids varying in osmotic pressure (hypotonic, isotonic, hypertonic) to which a vertical tube was attached. The change in height of fluid in the tube was taken as a measure of changes in middle ear fluid volume. A greater fluid volume reduction was seen with the hypotonic (1/5 saline) solution. A small volume increase was observed with the hypertonic solution. These results provide evidence that in these experimental conditions, water absorption due to osmotic gradients can contribute to middle ear fluid clearance.     

Prolonged conductive hearing loss in rat pups causes shorter brainstem transmission time.

A carefully controlled study was conducted in rats to determine whether a reversible conductive hearing loss during the neonatal period could induce changes in central conduction and thereby perhaps contribute to an understanding of learning problems seen in children following conductive hearing loss in infancy. Ear plugs were inserted from post-natal day 9 in rat pups and auditory nerve brainstem evoked responses were recorded in the presence of ear plugs and following their removal on post-natal day 23. The I-IV interpeak latency (brainstem transmission time) was significantly shorter in the experimental rats several days after plug removal (day 28) compared to untreated control rats. This difference was not related to residual conductive loss, nor to different body weights and was present even in response to equal sensation level stimuli, and was not present in adult rats with similarly induced conductive hearing losses. It seems therefore that conductive hearing loss in the young animal (critical period?) can induce changes in central auditory conduction and may be related to the findings of smaller brainstem auditory neurons in sound deprived animals. These results have implications for neonatal hearing loss in humans.     

Sources of frequency following responses (FFR) in man.

In order to study the sources and pathways which are responsible for the frequency following response (FFR), records were made in control subjects and in patients with special types of lesion and response. It has already been shown that the FFR in normal subjects to tone bursts with single onset phases is made up of a short latency cochlear microphonic potential (CM) and a longer latency neural component (neural FFR). No neural FFR could be recorded in patients with upper brain-stem lesions (absence of click-evoked responses from the inferior colliculus along with clinical signs of such a lesion). Their FFR was exclusively a cochlear microphonic potential, thus demonstrating that the neural FFR with a latency of 6 msec is generated in the region of the inferior colliculus. Also in subjects with large post-auricular muscle (PAM) responses, the PAM can contribute to the FFR, with a latency of 10 msec. In patients with high-tone hearing loss due to acoustic trauma, no CM could be recorded while a neural FFR with a latency of 6 msec was present. This indicates that the CM recorded by this technique may be generated in the basal turn. It also demonstrates that the pathway of the neural FFR begins in the apical turn of the cochlea.     

MATHEMATICAL EXPRESSION OF RELATIONSHIP BETWEEN AUDITORY BRAINSTEM TRANSMISSION TIME AND AGE

Brainstem transmission time (BTT) was studied in 71 subjects ranging in age from one day to 29 years in order to find a mathematical expression to best describe the relationship between BTT and age. The mathematical function which relates BTT to age is exponential. Using this data, the BTT confidence limit was calculated for subjects from birth through to eight years. Repeated recordings of auditory brainstem responses were performed in several children as they grew older and these verified the normal maturational processes of the brainstem structures in the developing infant and young child.     

Five-week red cell storage with preservation of 2,3 DPG

The 2,3 diphosphoglycerate (2,3 DPG) content of red cells stored in current anticoagulant-preservative products decreases rapidly after the first few days of storage, and by 3 weeks the red cells are essentially depleted of 2,3 DPG. Because ascorbic acid and ascorbate-2-phosphate (A-2-P) are effective in maintaining erythrocyte 2,3 DPG during liquid preservation, ascorbate was stabilized through autoclaving and subsequent storage by adding it as the trisodium salt of A-2-P to a phosphate-adenine-saline solution at a pH of 8.5 to 9.0. Red cell concentrates prepared from blood drawn into citrate-phosphate-double-dextrose were supplemented with the A-2-P additive solution (AS-4) and studied in vitro and in vivo. Mean 2,3 DPG values for 22 units were 147.6, 113.5, and 82.3 percent of initial value after storage for 3, 4, and 5 weeks, respectively. Maintenance of 2,3 DPG was at the expense of adenosine triphosphate (ATP), which fell to as low as 22.2 percent of initial value after 5 weeks. Despite the low ATP values, the 24 hour 51Cr-labeled red cell recoveries averaged 80.8 and 74.1 percent after 4 and 5 weeks of storage, respectively. The AS-4 system provides a red cell product with acceptable viability and improved oxygen off-loading function.     

Targeting health disparities: a model linking upstream determinants to downstream interventions

Certain social/environmental factors put some groups at extraordinary risk for adverse health outcomes, creating health disparities. We present a downward causal model, originating at the population level and ending at disease, with psychological and behavioral responses linking the two. This approach identifies how specific social environments "get under the skin" to cause disease, illustrated with the disparity in mortality from aggressive premenopausal breast cancer suffered by black women. Broadening our lens to consider the entire chain of causal factors, spanning multiple levels and interacting across the life span, heightens our ability to craft specific interventions to address group differences in health.