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Biomedical subjects

V Honrubia

Publications and source records attributed to V Honrubia.

At least 37 records · Page 2Linked to original sources

Quantification of the process of hair cell loss and recovery in the chinchilla crista ampullaris after gentamicin treatment.

The degree of ototoxic drug sensitivity and hair cell repair was determined in the chinchilla horizontal crista ampullaris after intraotic administration of gentamicin. Histological evaluation was made of 22 cristae ampullaris from one normal and six post-treatment (PT) animal groups killed at 1, 4, 7, 14, 28, and 56 days. New hair cell production was quantified, using the dissector technique. Transmission electron microscopy was used to investigate the ultrastructural characteristics of the hair cells in the regenerated epithelium. At 1 day PT, type I and II hair cells presented cytoplasmic vacuolization, swollen nerve calyces and 20% of type I and 18% of type II hair cells were lost. At 4 days PT, 95% of type I hair cells and 14% of type II hair cells had disappeared. In addition, most of the type II hair cells showed clumping of nuclear material. Nerve fibers were not found in the sensory epithelium, but were still observed below the basal lamina. Supporting cells appeared unaffected, maintaining their location in the crista. At 1 and 4 days PT, the damage to hair cells was more pronounced in the central region of the crista ampullaris. The degree of ototoxic damage at 7 days was similar to that of 14 days: no type I hair cells were present and most of the type II hair cells had disappeared; supporting cell nuclei began to occupy the apical part of the sensory epithelium and most of the nerve fibers had retracted. Quantitatively, 87 and 93% of type II hair cells were lost at 7 and 14 days PT, respectively. Initial signs of hair cell recovery began at 28 days PT; immature type II-like hair cells appeared, supporting cell nuclei began to align at the base of the sensory epithelium and nerve fibers penetrating the basal lamina were observed. No type I hair cells were found, but 40% of the normal number of type II hair cells were present. Hair cells appeared to regenerate in the peripheral areas of the cristae ampullaris first. At 56 days PT, an increase in the number of mature type II hair cells was present, supporting cells were aligned at the base of the epithelium, and more nerve fibers appeared to penetrate the basal lamina to the sensory epithelium. Although type I hair cells were absent from the epithelium 55% of the normal number of type II hair cells were present. At this time, more regenerated hair cells were located in the center of the cristae ampullaris as compared to the periphery. At the transmission electron microscopic level, type II hair cells at different stages of maturation were observed. Some exhibited mature stereocilia, a cuticular plate, and terminal endings with synaptic specialization opposing these hair cells. In conclusion, type I hair cells were more sensitive than type II hair cells to gentamicin intoxication (as they disappeared as early as 4 days PT). After 56 days PT, the number of type II hair cells reached 55% of normal. No type I hair cells had regenerated at this time. These results demonstrate quantitatively the differential ototoxic sensitivity and regenerative capacity of hair cells.

Animals↗

Intraotic administration of gentamicin: a new method to study ototoxicity in the crista ampullaris of the bullfrog.

A new method of local gentamicin administration was tested in the bullfrog inner ear to achieve ototoxic-induced hair cell destruction. Gelfoam pledgets soaked with known amounts of gentamicin were inserted into the perilymphatic cisterna of the bullfrog through a ventral surgical approach. A dose of 1.20 mg gentamicin, consistent with a perilymphatic concentration of 65 microg/ml, resulted in the desired ototoxic-induced hair cell damage, that is, complete hair cell destruction with minimal disruption of other components of the sensory epithelium. This study demonstrates that this is a useful and simple method to investigate the process of vestibular ototoxicity and hair cell regeneration, including aspects of hair cell destruction and repair.

Administration, Topical↗

Clinical-pathologic correlation in a patient with selective loss of hair cells in the vestibular endorgans.

We found a selective loss of vestibular hair cells in a patient followed for more than 10 years with imbalance and oscillopsia due to idiopathic progressive loss of vestibular function. Hearing function and cochlear hair cells were normal. The vestibulo-ocular reflex (VOR) gain at high frequencies was relatively maintained despite marked shortening of the dominant VOR time constant (to less than 500 ms). Ultrastructural examination of remaining hair cells showed mitochondrial abnormalities. The ultrashort VOR time constant probably resulted from changes in firing patterns of the primary afferent nerves due to loss of hair cells and impaired energy metabolism in remaining hair cells.

Adult↗

Vestibular neuritis: clinical-pathologic correlation.

Postmortem examination of the brain and temporal bones of a patient with well-documented vestibular neuritis showed selective neuronal loss in Scarpa's ganglia on the side with absent caloric response. There was loss of hair cells and an "epithelialization" of the utricular macule and semicircular canal cristae on the deafferented side, and synaptic density in the vestibular nuclei on the deafferented side was decreased compared with that on the normal side. All findings were consistent with an isolated viral infection of Scarpa's ganglia. This is the first description of the effects of chronic deafferentation on the vestibular sensory epithelia and the vestibular nuclei in a human being.

Aged↗

Histopathology of idiopathic chronic recurrent vertigo.

Vestibular neuritis is a degenerative neuropathy of the peripheral vestibular system. The etiology of this condition is uncertain, although it is generally believed to be viral. A small percentage of patients with vestibular neuritis have chronic recurrent episodes of vertigo. Detailed cytologic descriptions of acute or chronic vestibular neuritis are lacking, and no previous studies have reported evidence of chronic inflammation in human temporal bone specimens. The authors of this study examined temporal bone specimens from three patients with a history of chronic recurrent vertigo of unknown cause. Varying degrees of inflammation and destruction were seen in the vestibular system, and mild involvement of the cochlear system was noted. These findings are consistent with postinfectious inflammatory changes of the cochlear-vestibular system analogous to a postinfectious syndrome involving the central nervous system.

Cochlear Nerve↗

Quantitative evaluation of dizziness characteristics and impact on quality of life.

Patients attending an outpatient clinic with the complaint of dizziness were given a set of five items to rank the magnitude of the frequency and severity of their dizziness and the impact of dizziness on their quality of life. They were given instruments to evaluate their degree of anxiety and depression. The impact of frequency and severity on the patients' daily activities, on the quality of life, and on the fear of becoming dizzy was self-rated by the patient. The score on quality of life was compared with that provided by the physician in a blind questionnaire. The items that were developed addressed the physical, functional, and emotional impact of dizziness and can be considered promising for the evaluation of the patients' degree of overall impairment.

Adolescent↗

Projections of the individual vestibular end-organs in the brain stem of the squirrel monkey.

The central nervous system (CNS) projections of primary afferent neurons from individual vestibular receptors were studied using horseradish peroxidase (HRP) or biocytin labeling in 14 ears from 7 adult squirrel monkeys using the technique developed in the chinchilla (Lee et al., 1989, 1992). The specificity of labeling was verified by examining the location of the labeled fibers and cell bodies in the vestibular nerve and Scarpa's ganglion. Labeled fibers and cells were restricted to nerves and areas belonging to groups of cells in either the superior or the inferior ganglion of the vestibular nerve. In the vestibular nerve root, labeled primary afferent fibers also exhibited a receptor-dependent segregation at the entrance to the medulla. Fibers from the HSC and the SSC were found rostrally and those from the PSC and the SAC were found in the caudal area. The UTR fibers were situated intermediate between these two groups of fibers. (A bundle of fibers, probably vestibular efferents, was identified immediately rostrally and ventromedially to the UTR fibers.) The primary afferent fibers bifurcated into secondary ascending and descending fibers at the lateral border of the vestibular nuclei, forming a longitudinal rostrocaudal vestibular tract. The secondary fibers from individual end-organs occupied specific locations in the tract: the UTR fibers were dorsal to the SSC and the HSC fibers, PSC fibers were found most medially, and the SAC fibers occupied the lateralmost area. The secondary UTR fibers overlapped considerably with those of the SSC and the HSC. The orderly receptor-dependent segregation of fibers was more prominent in the descending tracts than in the ascending tracts. In the vestibular nuclei complex the location of the tertiary branches of various end-organs exhibited considerable overlap within the major vestibular nuclei (SN, superior nucleus; LN, lateral nucleus; MN, medial nucleus; DN, descending nucleus). There were still differences, however, in the projection pattern. Fibers from the SAC ran primarily in the lateral area, fibers from the SSC and the UTR were found ventromedially to the SAC fibers, and the HSC projected slightly medially to the fibers from the SSC. The PSC fibers projected most medially. The UTR and SAC sent numerous fibers to the cerebellum. Fibers from the semicircular canals projected through the rostrodorsal region of the SN and presumably also projected to the cerebellum. The precise termination of fibers was evaluated by studying the location of labeled boutons, which were identified in all major vestibular nuclei. Labeled boutons from all the receptors were in the rostral and central areas of the SN, and in the MN mainly in the rostral two-thirds. In the LN, boutons from all the receptors were in the rostroventral part, most of which were from the UTR and SAC. No labeled boutons were in the caudodorsal part of this nucleus. Labeled boutons in the DN primarily surrounded the descending tract fibers and were particularly prominent medially. In specimens in which superior vestibular nerve receptor organs were scratched vestibular efferent fibers were also labeled. These fibers traveled in the most ventral part of the vestibular nerve root and projected in the ventral aspect of the LN to labeled soma in the ipsilateral and contralateral brain stem. Specificity the in projection patterns of efferent fibers from different end-organs could not be ascertained.

Animals↗

Histological evidence for hair cell regeneration after ototoxic cell destruction with local application of gentamicin in the chinchilla crista ampullaris.

Two experiments were conducted to study the ototoxic effects of local gentamicin (GM) administration and the subsequent hair cell (HC) regeneration process in the chinchilla cristae ampullares (CA). In the first experiment, 3 different doses of GM (0.1, 0.2 and 1.2 mg) were administered by surgical implantation of GM-soaked Gelfoam pledgets in the perilymphatic space in the otic capsule of the left superior semicircular canal. The CA was histologically processed for light-microscopic examination. In the second experiment, 6 groups of 2 chinchillas each were treated with 0.1 mg of GM. To document cell proliferation and HC regeneration, Alzet micro-osmotic pumps were implanted in each chinchilla to deliver bromodeoxyuridine (BrdU) at 125 micrograms/h for 1 week. Chinchillas were subsequently killed at 1 and 4 days and 1, 2, 4 and 8 weeks post-treatment (PT). The CA was processed for light microscopy and BrdU immunocytochemistry. In the first experiment the smallest dose produced damage restricted to HCs alone, while the medium and large doses produced severe damage in the sensory epithelium, including supporting cells and HCs. Results in the second experiment demonstrated that at 1 and 4 days PT the HCs showed extensive damage, including clumping of nuclear material. By 4 days PT the supporting cell nuclei lost their monolayer configuration. Calyceal terminals appeared empty, and vacuolized remnants of nerve calyces were evident in the basal portion. At 1 week PT complete disappearance of HCs from the sensory epithelium was evident, and there was cytoplasmic extrusion into the endolymphatic space. At 2 weeks PT there was complete HC loss, the supporting cell nuclei were scattered randomly in the crista, and the nerve fibers were retracted from the sensory epithelium. At 4 weeks PT there was evidence of sensory epithelium repair and HC regeneration. Short cells resembling type-II HCs were evident in the surface of the sensory epithelium. At 8 weeks PT the number of HCs increased in a uniform fashion on the surface of the sensory epithelium, and the supporting cell nuclei were realigned on the basal membrane. Nerve fibers with growth cones penetrated the basal membrane. Supporting cell proliferation was evident by the presence of mitotic figures and BrdU immunoreactivity in the chromatin material of dividing cells at 2 weeks PT. The labeling was more evident in newly formed cells at 4 and 8 weeks PT. These results demonstrate that in chinchillas the vestibular organs have the capacity of self-repair and the process includes HC regeneration after local administration of GM. The overall process involves changes in different cells in the sensory epithelium and neural elements, all of which show modifications with an orderly pattern.

Animals↗

Effect of vestibular nerve section on cytochrome oxidase activity in the vestibular ganglion cells of the squirrel monkey.

Cytochrome oxidase (CO) activity of the vestibular ganglion cells of the squirrel monkey was demonstrated histochemically under normal and experimental conditions. Under general anesthesia, right vestibular nerve section was performed on adult squirrel monkeys between the vestibular ganglion and brain stem. The left side was left intact and was used as a within-animal normal control. One squirrel monkey that did not undergo vestibular nerve section was also included in the normal group. Following a survival period of seven months, neurons in the vestibular ganglion of both sides were examined. In the normal control sides, a significant negative correlation between the size of the neuron and its optical density for CO stain was observed. Many neurons in the vestibular ganglion survived after vestibular nerve section, but their cell sizes and optical densities of CO stain decreased compared with those of the control side.

Animals↗

Contemporary vestibular function testing: accomplishments and future perspectives.

The development of a standard test battery for the evaluation of vestibular function required a variety of preliminary investigations about the technical and physiologic foundations of the tests. The most important technologic development was the creation of computerized methods, including hardware and software capabilities. The designs of tests were based on physiologic and diagnostic considerations, as demonstrated in experiments on normal subjects and patients. Although time tested and sound, the available test battery satisfies only a limited number of requirements for comprehensive evaluation of vestibular function. This article describes the list of accomplishments, the state of the present limitations, and the needs for the future.

Computers↗

Persistent direction-changing positional nystagmus: another variant of benign positional nystagmus?

Positional nystagmus that does not fatigue, persists as long as the position is held, and changes direction in different head positions has typically been attributed to central vestibular lesions. We recently studied three patients who presented with positional nystagmus having these features but almost certainly of benign peripheral origin. All three had an initial history typical of benign positional vertigo and, in two, the persistent direction-changing positional nystagmus occurred after the patient underwent a maneuver to remove debris from the posterior semicircular canal. The positional nystagmus profile and clinical course are consistent with the debris leaving the posterior semicircular canal and becoming attached to the cupula of the horizontal semicircular canal.

Aged↗

Characterization of vestibular potentials evoked by linear acceleration pulses in the chinchilla.

The objective of this study was to improve vestibular evoked potentials as a qualitative parameter for vestibular function in small laboratory animals. Linear upward acceleration pulses (up to 8 g within 1 ms) were applied to the head of anesthetized chinchillas. Electrophysiologic responses recorded by a chronically implanted electrode within the facial nerve canal consisted of an initial negative potential, labeled N1, within the first millisecond following the onset of acceleration. This potential was followed by a series of positive and negative potentials found to be highly labile to acoustic masking. The initial negative potential was only minimally sensitive to acoustic masking and persisted following surgical cochlear ablation, but completely disappeared following administration of potassium chloride into the inner ear. Recorded from the contralateral ear, N1 was unaffected by these procedures. Amplitudes of N1 decreased with attenuating stimulus intensity (1.45 microV/dB), whereby N1 latencies slightly increased (-0.015 ms/dB). These data, when coupled with the ability to completely abolish N1 with potassium intoxication while the contralateral ear remained intact, indicate that this potential represents electrophysiologic activity resulting from activation of the ipsilateral vestibular labyrinth.

Acceleration↗

Interlaboratory variability of rotational chair test results. Interlaboratory Rotational Chair Study Group.

Test-retest reliability of rotational chair testing for a single facility has previously been examined by others. The actual data analysis methods, however, have received far less attention. The variety of both hardware and software currently used theoretically may affect the results for a given subject tested at different facilities. The purposes of this study were, first, to quantify the amount of variability in the analysis of identical raw data files at multiple rotational chair testing facilities by using automated analysis; second, to evaluate the effect of operator intervention on the analysis; and third, to identify possible sources of variability. Raw data were collected from 10 normal subjects at 0.05 Hz and 0.5 Hz (50 degrees per second peak velocity). Diskettes containing raw electro-oculogram data files were then distributed to eight participating laboratories for analysis by two methods: (1) using automated analysis algorithms and (2) using the same algorithms but allowing operator intervention into the analysis. Response parameters calculated were gain and phase (re: velocity). The SD of gain values per subject for automated analysis ranged from 0.01 to 0.32 gain units and of phase values from 0.4 to 13.7 degrees. For analysis with operator intervention, the SD of gain values ranged from 0.02 to 0.10 gain units and of phase values from 0.4 to 4.4 degrees. The difference between automated analysis and analysis with operator intervention was significant for gain calculations (p < 0.02) but not for phase calculations (p > 0.05). This study demonstrates significant variability in automated analysis of rotational chair raw data for gain and phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Dynamic visual acuity: a test for oscillopsia and vestibulo-ocular reflex function.

A method has been developed of clinically quantifying dynamic visual acuity (DVA), the acuity during imposed head motion in the pitch axis. In this method, visual acuity is measured using a computer-controlled projection system during vertical, sinusoidal relative motion either of the optotypes (the letters to be read) or of a servodriven swinging chair in which subjects are seated. In normal persons, the vestibulo-ocular reflex (VOR) functions adequately during imposed head movements to limit retinal image instability, making DVA independent of head velocity. During head movements the wearing of telescopic spectacles, which magnify the visual effects, can overwhelm even normal visual-vestibular interactions, producing retinal image instability leading to creation of artificial experimental oscillopsia in normal subjects. With the head stationary, optotype motion at frequencies and velocities beyond the capabilities of visual tracking also results in retinal image motion. Using these methods, DVA for both optotype and head motion was found to be degraded in a predictable fashion when the velocity of the image on the retina exceeded 2 degrees per second. In two patients with total peripheral vestibular loss, DVA was markedly impaired during head motion. As a result of the VOR deficit, this impairment of DVA was observed, even without the use of telescopic spectacles, and was predictably related to the velocity of imposed head motion. Dynamic visual acuity during imposed head motion is a quantitative and clinically feasible measure of oscillopsia that reflects functionally significant abnormalities of the VOR.

Adult↗

Horizontal semicircular canal variant of benign positional vertigo.

We report the clinical features and results of quantitative eye-movement testing in 13 patients with episodic positional vertigo and nonfatiguing direction-changing horizontal positional nystagmus (beating to the right with the head turned to the right and beating to the left with the head turned to the left). The benign history and lack of associated neurologic findings support a peripheral localization of the lesion. This syndrome probably represents a horizontal semicircular canal variant of benign positional vertigo. Free-floating debris in one horizontal canal may explain many of the clinical and oculographic findings.

Adult↗

The galvanically-induced vestibulo-ocular reflex in the cat.

Rotatory vestibular input is processed by receptor organs and relayed along the vestibular nerves to a central processor, whence the vestibulo-ocular reflex (VOR) is generated. Electrical stimuli applied to the labyrinth can bypass receptors and stimulate the nerve directly, thereby generating horizontal eye movements (EVOR). It was our purpose to mathematically relate the EVOR to the VOR in an effort to generate a parameter by which the experimental effects of ototoxins on the inner ear can be evaluated. A feline preparation was created in which the VOR and EVOR were measured in response to various sinusoidal stimuli. A detailed comparison between VOR and EVOR with respect to gain and phase was performed. From analysis of the data, the differential sensitivity to rotatory amplitude with respect to electrical amplitude was proposed as this parameter.

Animals↗

Morphologic and quantitative study of the efferent vestibular system in the chinchilla: 3-D reconstruction.

An HRP study of the EVN has been performed. Three groups of somas have been identified: Those located in the proximity of the vestibular nuclei, those sandwiched between the facial genu and the IVth ventricle, and those in the RF, surrounding the abducens nucleus. The number of somas is greater in the contralateral brain-stem side. Axons could be followed through the midline, but could not be traced to a labelled soma. A 3-D reconstruction of the EVN within the brain stem is presented.

Animals↗