Spiral ganglion neuron loss following organ of Corti loss: a quantitative study.

The packing density of spiral ganglion neurons was measured in 2.5- and 13-15-month-old guinea pigs, in guinea pigs at various times after drug-deafening or acoustic trauma, and in Waltzing guinea pigs of various ages. Analysis of variance and Duncan's new multiple range tests were used to determine significant differences between treatment/survival groups. Spiral ganglion neurons in young and old normal ears did not have significantly different packing densities. Drug-deaf guinea pigs showed a significant loss of neurons by 2 weeks following treatment, a further significant loss by 2 months, and a marginally significant loss between 4 and 8 months. The neuronal population was then stable through 15 months, at about 13% of normal. Acoustic trauma ears showed the first significant loss isn the lower second turn at 1 month. Long-term (12-14 months post-exposure) trauma ears were highly variable. Waltzers lost about 50% of their normal neuronal population between 4 and 8 months; they showed an unexpected greater-than-normal density at 2 months, possible explanations of which are discussed. Thus, loss of the organ of Corti from various causes results in a slow but progressive loss of spiral ganglion neurons, the time course of which varies with the type of cochlear insult.

A systems model for food purchasing.

The approach taken in this paper of isolating seasonal characteristics of products and then using that information to determine when those products should be ordered to minimize the system's purchasing costs appears to be valid. A drawback to using this approach, however, is acquiring appropriate data. The authors used data which they believed to be appropriate for thier market purchasing environment but which are not necessarily valid for other locations and/or environments. The prospective user of this model must find and obtain data suitable for the environment and isolate those products which appear seasonal. Only a small percentage of the items used possess any seasonal properties. There is also the obvious problem of using past data to determine future outcomes. Past price patterns do not necessarily continue into the future, although they should be at least indications, barring unusual farm and/or market situations. As with all decision modeling approaches, however, this model should be followed with caution. While the approach is valid, the procedure is no substitute for knowledgeable management of food service functions. Results from the model should provide additional input to guide food purchasing decisions but should not be used unequivocably. When property used, however, this procedure will allow food buyers to come closer to the goal of optimally purchasing food products from a systems point of view then is currently possible.

Conductive hearing loss affects the growth of the cochlear nuclei over an extended period of time.

During normal growth in CBA/J mice, the volume of dorsal and ventral cochlear nuclei change very little between 1 and 3 days of age; then more than double between 6 and 12 days of age. After 12 days, the rate of growth declines, but growth continues through at least 90 days. The globular cells of the ventral cochlear nucleus also double their soma areas between 6 and 12 days, but then grow no more. The number of ventral cochlear nucleus neurons containing Nissl substance doubles between 6 and 12 days of age and then remains stable. This increase in neuronal numbers is probably caused by differentiation of neuroblasts into neurons, not by mitoses. Conductive losses from 4 to 45 days, and from 24 to 45 days, both result in reduced volume of the ventral cochlear nucleus, but have no effect on the volume of the dorsal cochlear nucleus. Globular cell area is affected by a conductive loss from 4 to 45 days of age, but not by a conductive loss from 24 to 45 days. Therefore, conductive losses affect neuropil growth beyond the time when soma size is no longer affected by these losses.

Sound amplification negates central effects of a neonatal conductive hearing loss.

Neonatal CBA/J mice with external auditory meati removed were raised in a sound-amplified environment. If amplification continued until sacrifice at 24 or 45 days of age, both cochlear nuclear volumes and cross-sectional areas of VCN globular cells were of normal size; without amplification both measurements were significantly reduced.

Late onset of auditory deprivation does not affect brainstem auditory neuron soma size.

Neuronal soma sizes from normal mice, mice with conductive losses from 45 days, and avocal mice subjected to sound deprivation from 45 days, were studied at 90 days, revealing no significant differences between groups for cochlear nuclear globular cells, or cells of medial nucleus of trapezoid body or inferior colliculus.

The spiral ganglion and cochlear nuclei of deafness mice.

Deafness mice (dn/dn) never develop hearing, but, except for the associated physical defects, have no other known abnormalities. For this study, cochleas and brains of five adult homozygotes (dn/dn) and five adult heterozygotes (+/dn), matched by weight and sex, were prepared for serial section light microscopy. In the homozygotes, the organ of Corti was totally degenerated basally, gradually improving toward the apex where supporting cells, border cells and pillar cells were present; however, the stria vascularis was dystrophic in the apex. The saccular macula was atrophied or dystrophic in seven of the ten homozygote ears. The homozygotes had only 23% of the number of spiral ganglion cells found in the heterozygotes, but they appeared robust. In six of the ears of each group there was clumping of apical spiral ganglion neurons. In the homozygotes, the volume of Rosenthal's canal was 121%, that of the dorsal nuclei was 90%, and that of the ventral cochlear nuclei was 63% of the comparable volumes in heterozygotes. The globular cells of the homozygote ventral cochlear nucleus were 72% of the size of those of heterozygotes. These quantitative morphological abnormalities of the homozygote spiral ganglion and cochlear nuclei may result from organ of Corti atrophy.

Exogenous GM1 ganglioside effects on conductive and sensorineural hearing losses.

Both CBA/J mice with neonatal cochlea removals and CBA/J mice with neonatal atresias of the external auditory meatus have significantly smaller ventral cochlear nucleus is greater in the mice with cochlea removals, but the soma area reduction is greater in the mice with external auditory meatus atresias. GM1 gangliosides were subcutaneously injected daily into a group of CBA/J mice with conductive hearing loss caused by neonatal removals of their left external auditory meatus, and into a group of CBA/J mice unilaterally deafened by left cochlea removals. In the mice with conductive hearing loss, the ganglioside treatment significantly ameliorated the atrophy of spiral ganglion neurons, ventral cochlear nucleus neurons, and ventral cochlear nucleus volume. In unilaterally deafened mice, the ganglioside treatment had no measurable effect on the atrophy of ventral cochlear nucleus neurons or of ventral cochlear volume. It is suggested that GM1 ganglioside treatment potentiates growth factors which sustain spiral ganglion integrity and that this sustained activity of the spiral ganglion in turn maintains the integrity of the cochlear nuclei.

Neonatal conductive hearing loss does not compromise brainstem auditory function and structure in rhesus monkeys.

The effect of conductive hearing loss on the maturation of the auditory pathway was evaluated using the auditory brainstem response (ABR) in rhesus monkeys. Ten newborn rhesus monkeys were assigned to control (N = 4), unilateral hearing loss (N = 3), or bilateral hearing loss (N = 3) groups. Hearing loss was created by surgically excising a 3 mm section of the external auditory canal and suturing the canal. Auditory brainstem responses to click stimuli were recorded prior to and after the surgical procedure and bi-monthly or monthly for a 14 month follow-up period. Results showed that after surgery all ears developed an estimated 30-50 dB conductive hearing loss which was retained throughout the follow-up period. Contrary to expectations, the latencies of the ABR component waves decreased with age in all ears. When adjusted for hearing level, there were no differences between ears in maturation of the component waves of the ABR. These data suggest that, in primates, a conductive hearing loss does not affect the maturation of those aspects of the auditory pathway reflected in the ABR. Furthermore, the conductive losses were not accompanied by any discernible change in the neuronal sizes of brainstem auditory neurons or the volume of the cochlear nuclei.

Does electrical stimulation of deaf cochleae prevent spiral ganglion degeneration?

Thirty-six drug deafened guinea pigs were studied to determine how electrical stimulation of the cochlea affects spiral ganglion cell (SGC) survival. Animals were divided into two groups, extracochlear and intracochlear stimulation, and each group was further divided into four stimulus subgroups: no stimulation (implanted controls), the inferior colliculus electrically evoked potential (ICEEP) threshold-2 dB, ICEEP threshold+2 dB, and ICEEP threshold+6 dB. Stimuli consisted of 200 micros/phase charge balanced biphasic current pulses presented at 100 pulses per second using monopolar stimulation. Animals were stimulated 5 h/day, 5 days per week, for 8 weeks. The animals were then perfused and the cochleae serially sectioned at 4 microm saving every 8th section. We counted the number of intact SGCs, those containing a nucleus with chromatin, in each 20% segment of the cochlea and also measured SGC densities (number of neurons per mm2 of Rosenthal's canal). The number of surviving spiral ganglion neurons was not significantly different (P > 0.05) between the implanted and the unimplanted ears in any of the experimental groups. However, the spiral ganglion neuron densities were significantly elevated in the electrically stimulated ears (P < 0.001) but not in the implanted but not chronically stimulated ears (P > 0.05). We measured the volume of Rosenthal's canal in one subgroup (ICEEP threshold+2 dB) and found a decrease in this volume in the stimulated ear compared to the unstimulated ear (P < 0.01). These findings support the hypothesis that chronic monopolar electrical intracochlear or extracochlear stimulation is not a neurotrophic factor, increasing spiral ganglion neuron survival, but instead causes a narrowing of Rosenthal's canal that accounts for the increased spiral ganglion neuronal densities seen in the stimulated cochleae.

Morphological and electrophysiological study of the inner ear and the central auditory pathways following whole body fetal irradiation.

Pregnant CBA/CBA mice were whole body irradiated with 2 Gy on the 13th or 16th day of gestation, respectively. The exposed fetuses were raised to an age of 21 postnatal days. Auditory brainstem recordings of threshold levels showed a considerable elevation independent of if irradiation had been performed on either the 13th gestational day or the 16th gestational day. In exposed animals a latency difference occurs in the peaks that increases from peak 1 to peak 5, measuring in peak 5 up to 1.16 ms. Also the peak-to-peak length of waves 1-5 increases in irradiated animals. Scanning electron microscopy of the cochleae showed varying degrees of stereociliary derangement of both outer and inner hair cells, particularly in cochleae where irradiation had been performed on the 13th gestational day, but not loss of hair cells. Light microscopic analysis of auditory brainstem nuclei revealed normal conditions except that in inner ears exposed on the 16th gestational day the flocculus was fused to the lateral surface of the anterior ventral cochlear nucleus. It is concluded that the elevated threshold levels in irradiated animals are most likely due to pathological changes in the peripheral receptor organ whereas the increased latencies and the increased peak-to-peak length likewise reflect functional changes in the brainstem auditory nuclei.

Mice heterozygous for the deafness gene have normal auditory thresholds.

Cochlear degeneration in the early postnatal period has been reported as a homozygous recessive mutation in deafness (dn/dn) mice of the curly-tail stock. Heterozygous (+/dn) mice of the same population exhibit hearing when tested by the Preyer reflex, and their cochlear morphology appears normal by light microscopy. However, whether the heterozygote's unmatched recessive deafness allele has deleterious effects not detected by this reflex has not been examined. This study compares the ABR thresholds of presumed homozygous dominant (+/+) and known heterozygous (+/dn) deafness mice, as well as CBA/J mice. Hearing thresholds in the heterozygotes were not significantly different from those of presumed homozygotes or CBA/J mice. A 'generational backtracking' method was used to increase the probability of identifying homozygous (+/+) animals of the curly-tail strain.

Auditory brainstem responses in neonatally sound deprived CBA/J mice.

Auditory brainstem responses (ABR) from ten normal (3 males, 7 females) and ten environmentally sound deprived CBA/J mice (6 males, 4 females) were elicited by 30 dB HL click stimuli delivered via specially constructed, matched insert earphones. The mice were tested at 44-49 days of age under chloral hydrate sedation using an electrode montage of vertex/linked bilateral bullae/presacrum. The deprived mice were killed immediately after testing and serial transverse sections were prepared from their brains. Examination of globular cells of the ventromedial ventral cochlear nuclei revealed significantly smaller cross-sectional areas of these cells than in previously studied normal mice. Although monaural thresholds did not differ between the two groups, significantly shorter mean latencies were observed in the ABRs of the sound deprived group in wave I as well as in the interpeak latencies of the later ABR components (I-IV, I-V, and III-V). These electrophysiologic alterations in brainstem conduction presumably reflect the anatomical changes demonstrated in neonatally sound deprived mice.

Auditory brainstem responses of CBA/J mice with neonatal conductive hearing losses and treatment with GM1 ganglioside.

Exogenous administration of GM1 ganglioside to CBA/J mice with a neonatal conductive hearing loss ameliorates the atrophy of spiral ganglion neurons, ventral cochlear nucleus neurons, and ventral cochlear nucleus volume. The present investigation demonstrates the extent of a conductive loss caused by atresia and tests the hypothesis that GM1 ganglioside treatment will ameliorate the conductive hearing loss. Auditory brainstem responses were recorded from four groups of seven mice each: two groups received daily subcutaneous injections of saline (one group had normal hearing; the other had a conductive hearing loss); the other two groups received daily subcutaneous injections of GM1 ganglioside (one group had normal hearing; the other had a conductive hearing loss). In mice with a conductive loss, decreases in hearing sensitivity were greatest at high frequencies. The decreases were determined by comparing mean ABR thresholds of the conductive loss mice with those of normal hearing mice. The conductive hearing loss induced in the mice in this study was similar to that seen in humans with congenital aural atresias. GM1 ganglioside treatment had no significant effect on ABR wave I thresholds or latencies in either group.

Auditory systems of Heteromyidae: postnatal development of the ear of Dipodomys merriami.

Serial histological sections of kangaroo rats of postnatal ages 0-, 3-, 7-, 10-, and 14-days were prepared and studied. At birth the middle ear is mostly filled with mesenchyme and small in size, having only a small hypotympanum and a very small epitympanic recess. During the first postnatal two weeks, much of the hypertrophy found in the adult middle ear develops. Because an entotympanic element is nev er formed, the previously called entotympanic chamber is here renamed the hypotympanum. The epitympanic recess greatly expands to form what has been called the dorsal (or anterior) mastoid sinus. Since this chamber has no relation to the mastoid, it is here renamed the epitympanum. Posteriorly, the previously called posterior mastoid sinus develops from the growth of the hypotympanum into and beyond the region of the posterior and horizontal semicircular canals. In development and adult position it is comparable to the primate antrum and so is here renamed the antrum. At birth the organ of Corti is very immature but its major cell types can be identified. During the first two weeks of development the following events occur: (1) the vas spirale disappears, (2) the inner spiral sulcus cells atrophy, (3) the hair cells and supporting cells mature, (4) the cells of Hensen differentiate with their apical processes elevating the reticular lamina, (5) the innermost cell of Claudius migrates under and supports the Hensen's cells, and (6) the hyaline mass of the zona pectinata of the basilar membrane loses its connective tissue cells and expands in size. The developmental events support the previous description and identification of Hensen's and Claudius' cells.

Auditory systems of Heteromyidae: functional morphology and evolution of the middle ear.

Middle ears (515) from 26 species of the rodent family Heteromyidae - genera Dipodomys, Microdipodops, Perognathus, and Liomys - were studied both grossly and histologically, for qualitative and quantitative comparisons. Middle ear modifications characteristic of each genus are qualitatively described. Quantitative comparisons are made among the 26 species in the study. Some correlations between middle ear size and other measurements are discussed. The middle ear is an acoustical transformer that for best efficiency must match the impedance of the cochlea to the impedance of the air in the external auditory meatus. It accomplishes this by a pressure increase and a velocity decrease through the combined effects of the lever and areal ratios; however, because the important consideration is a matching of two impedances rather than an absolute pressure increase, the pressure transformer ratio is a less informative measure of the middle ear's efficiency than is the impedance transform ratio. The impedance transformer mechanism is explained (from a morphological point of view), and equations are presented. Dipodomys, Microdipodops, and Perognathus have a theoretical transmission (at the resonant frequency) of 94-100% of the incident acoustical energy; Liomys, 78-80%. The areal ratio of stapes footplate to 2/3 tympanic membrane is remarkably constant among the species, varying only from 0.04 to 0.07: in Dipodomys and Microdipodops this small ratio is due to the very large tympanic membrane; in Perognathus and Liomys it is due to the extremely small stapes footplate. The lever ratio of incus to malleus varies from 0.28 to 0.33 in Dipodpmys and Microdipodops, from 0.37 to 0.46 in Perognathus, and from 0.55 to 0.60 in Liomys. In addition, the middle ear volumes and the morphology of tympanic membrane, ossicles, ligaments, and muscles, all combine to minimize both mass and stiffness. All these data suggest middle ear mechanisms which are very efficient over a broad frequency range. The middle ear modifications found in heteromyids are adaptive in predator avoidance, especially in areas of little natural cover; nevertheless, contrary to expectations, there is no firm relationship between habitat and the extent of these modifications in the 26 species. However, environment did apparently plan an important role in the evolution of the family, and this is discussed.

Anatomical consequences of CO2 laser surgery of the guinea pig ear.

A modified American Optical (Model 100) CO2 laser was used to produce lesions in the tympanic membranes, ossicles, and cochlear capsules of guinea pigs. Even with the lowest available intensities and durations (0.4 watts, 50 msec), there was damage to the inner ear. Although laser surgery of the ear can avoid mechanical trauma and bleeding as well as increase accuracy, the use of commercial lasers in ear surgery should be avoided until a proven unit is available.

Effects of an amine fluoride mouthrinse and dentifrice on the gingival health and the extent of plaque of school children.

A study to test the efficacy of two amine fluoride products in reducing the extent of plaque and the degree of gingivitis was conducted with 6th-grade school children in Pensacola, Florida. The treatment regimens consisted of a daily supervised mouthrinse at school and the ad libitum home use of a dentifrice. Examinations were conducted at 12-week and 20-week intervals after the treatment had begun. There was no recognizable difference between the plaque and gingival reductions achieved with the use of the amine fluoride dentifrice or mouthrinse when compared either with their inorganic counterparts or with placebo treatment vehicles

Voxel significance mapping using local image variances in subtraction ictal SPET.

Subtraction ictal SPET co-registered to MRI (SISCOM) has been shown to aid epileptogenic localization and improve surgical outcome in partial epilepsy patients. This paper reports a method of identifying significant areas of epileptogenic activation in the SISCOM subtraction image, taking into account normal variation between sequential 99Tcm-ethyl cysteinate diethylester SPET scans of single individuals, and attempts to assess the clinical value of statistical mapping in subtraction SPET. Non-linear inter-subject registration is used to combine a group of subtraction images into a common anatomical framework. A map of the pixel intensity standard deviation values in the subtraction images is created, and this map is non-linearly registered to a patient's SISCOM subtraction image. Pixels in the patient subtraction image were then evaluated based upon the statistical characteristics of corresponding pixels in the atlas. SISCOM images created with the voxel variance method were rated higher in quality than the conventional image variance method in 15 patients. No difference in localization rate was observed between the voxel variance mapping and image variance methods. The voxel significance mapping method was shown to improve the quality of clinical SISCOM images.

Substance use among Dutch dental students.

OBJECTIVES: The objectives were to assess the prevalence of substance use among Dutch dental students and to determine their attitudes about substance use and its consequences. METHODS: In association with a national study of drug use among US dental students, a questionnaire was translated from English into Dutch and administered to dental students at two dental schools in The Netherlands. Students received an anonymous 115-item questionnaire in the fall of 1996. RESULTS: Alcohol was the students' drug of choice for lifetime (95%), past year (94%) and past month (88%) use. No significant correlations were found between alcohol use and gender, schools, and years in dental education. In the past month, 58% of students reported drinking on 5 or more days; 53% had 5 or more drinks on the same occasion, 20% had 5 or more drinks on the same occasion on 5 or more days; and 17% reported getting drunk at least monthly. Prevalence rates for past month use of tobacco was 24% and marijuana, 4%. Male students smoked twice as much as females, with significant differences found for all three periods of use (X2>19.00, P<0.01). When asked whether their schools offered policies and education programs on alcohol and other drugs, 52% of students reported that these were not available. CONCLUSIONS: Dental schools should develop effective programmes to educate students about responsible use of alcohol and other licit and illicit drugs. Schools should also inform students about their susceptibilities to substance abuse and dependency.

Reversible conductive hearing loss in mice.

Fibrin tissue adhesive was injected into the right ears of four 7-week-old CBA/J mice. Auditory brain stem responses (ABRs) were used to monitor changes in auditory sensitivity over the next 26 days, after which the middle ears and cochleas were examined histologically. Mean maximum ABR threshold shifts were as great as 36 dB, and were larger for higher frequencies than for lower. Maximum shifts occurred between 1 and 8 days; by 26 days, thresholds had returned to intensity levels observed before injection.