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Biomedical subjects

E L Smith

Publications and source records attributed to E L Smith.

At least 37 records · Page 2Linked to original sources

Effects of experimental glaucoma in macaques on the multifocal ERG. Multifocal ERG in laser-induced glaucoma.

Multifocal ERGs (MERGs) of 5 adult monkeys (Macaca mulatta) with inner retinal defects caused by laser-induced glaucoma were compared to MERGs from 3 monkeys with inner retinal activity suppressed pharmacologically. MERGs were recorded with DTL fiber electrodes from anesthetized monkeys. Stimuli consisted of 103 equal size hexagons within 17 degrees of the fovea. Stimuli at each location passed through a typical VERIS m-sequence of white (200 cd/m2) and black (12 cd/m2) presentations. In animals with laser-induced glaucoma, visual field sensitivity was assessed by static perimetry using the Humphrey C24-2 full-threshold program modified for animal behavior. Inner retinal (amacrine and ganglion cell) activity was suppressed by intravitreal injection of TTX (4.7-7.6 microM) and NMDA (1.6-5 mM). In normal eyes the first order response (1st order kernel) was larger and more complex, with more distinct oscillations (>60 Hz) in central than in peripheral locations. The 2nd order kernel also was dominated by oscillatory activity. There were naso-temporal variations in both kernels. Pharmacological suppression of inner retinal activity reduced or eliminated the oscillatory behavior, and naso-temporal variations. The 1st order kernel amplitude was increased most and was largest at the fovea. Removed inner retinal responses also were largest at the fovea. The 2nd order kernel was greatly reduced at all locations. In eyes with advanced glaucoma, the effects were similar to those produced by suppressing inner retinal activity, but the later portion of the 1st order kernel waveform was different, lacking a dip after the large positive wave. Visual sensitivity losses and MERG changes both increased over the timecourse of glaucoma, with changes in the MERG being more diffusely distributed across the visual field. We conclude that 1st and 2nd order responses of the primate MERG can be identified that originate from inner retina and are sensitive indicators of glaucomatous neuropathy.

Animals↗

Effect of onset age of strabismus on the binocular responses of neurons in the monkey visual cortex.

PURPOSE: By 6 weeks of age, neurons in the monkey's primary visual cortex acquire qualitatively adult-like binocular response properties and behaviorally stereopsis emerges. In this study, it was determined whether the onset of strabismus has a more severe impact on cortical binocularity before or after this critical developmental age. METHODS: Infant monkeys were fit with a light-weight helmet which held a total of 27 diopters of base-in prisms in front of their two eyes for a fixed period of two weeks. For one group of infant monkeys, prism-rearing began at 2 weeks of age and for a second group, the onset was at 6 weeks of age. Immediately after the rearing period, i.e., at 4 weeks and 8 weeks of age, respectively, extracellular single-unit recording methods were used to determine the nature and severity of alterations in the binocular response properties of V1 neurons. Dichoptic sinewave gratings were used as visual stimuli. RESULTS: In comparison to normal age-matched infants, V1 neurons in both strabismic groups exhibited reductions in sensitivity to interocular spatial phase disparities (disparity sensitivity) and a higher prevalence of binocular inhibitory interactions (binocular suppression). However, the reduction in disparity sensitivity and the magnitude of binocular suppression were much greater in the late (6-8 weeks) than the early (2- 4 weeks) onset group. CONCLUSIONS: Discordant binocular signals due to brief periods of early strabismus have more serious effects on the development of binocular properties of V1 neurons if they occur shortly after rather than before the emergence of stereopsis (i.e., when the binocular connections are relatively more mature but the visual cortex still shows a high degree of plasticity).

Age of Onset↗

Vision-dependent changes in the choroidal thickness of macaque monkeys.

PURPOSE: To determine whether changes in the eye's effective refractive state produce changes in the thickness of the choroid in infant monkeys. METHODS: Normal developmental changes in choroidal thickness were studied in 10 normal rhesus monkeys. Hyperopia or myopia was induced by rearing 26 infant monkeys with either spectacle or diffuser lenses secured in front of one or both eyes. The treatment lenses were worn continuously beginning at approximately 3 weeks of age for an average of 120 days. Refractive status and ocular axial dimensions, including choroidal thickness, were measured by retinoscopy and high-frequency A-scan ultrasonography, respectively. RESULTS: Three lines of evidence indicate that the normal increase in choroidal thickness that occurs during early maturation can be altered by the eye's refractive state. First, in monkeys experiencing form deprivation or those in the process of compensating for imposed optical errors, choroidal thickness and refractive error were significantly correlated with eyes developing myopia having thinner choroids than those developing hyperopia. Second, the choroids in eyes recovering from binocularly induced myopia increased in thickness at a faster rate than the choroids in recovering hyperopic eyes. Third, monkeys recovering from induced anisometropias showed interocular alterations in choroidal thickness that were always in the appropriate direction to compensate for the anisometropia. These changes in choroidal thickness, which were on the order of 50 microm, occurred quickly and preceded significant changes in overall eye size. CONCLUSIONS: Changes in the eye's effective refractive state produce rapid compensating changes in choroidal thickness. Although these choroidal changes are small relative to the eye's refractive error, they may play an important role in the visual regulation of axial growth associated with emmetropization.

Animals↗

Glaucoma in primates: cytochrome oxidase reactivity in parvo- and magnocellular pathways.

PURPOSE: To evaluate the differential effects of ganglion cell depletion from experimental glaucoma on the relative metabolic activities of neurons in the parvo (P)- and magno (M)-cellular visual pathways of the macaque visual system. METHODS: Monocular experimental glaucoma was induced in monkeys (Macaca mulatta and M. fascicularis) by applying a laser to the trabecular meshwork to increase intraocular pressure (IOP). After other behavioral and electrophysiological studies, the lateral geniculate nuclei (LGNs) and the primary visual cortices were analyzed for functional afference from surviving ganglion cells, indicated by cytochrome oxidase (CO) histochemistry. RESULTS: CO reactivity (COR) indicated a general reduction in neural metabolism with increasing severity of glaucoma. COR in the LGNs was reduced to the same degree in both the P- and M-cellular layers. In layer 4Cbeta of the V1 cortex, the reactivity was always reduced more than in the layer 4Calpha division. CONCLUSIONS: Experimental glaucoma in monkeys reduces visual afference to the central nervous system, thereby reducing the metabolic drive as indicated by COR. The detrimental effect of glaucoma did not appear to be any greater for the M-cell, rather than the P-cell pathway in the LGN or in the visual cortex. Both are affected by the duration and severity of the experimental glaucoma. Overall, the alterations in metabolism of neurons in the parallel visual pathways supplied by the Palpha and Pbeta ganglion cells do not suggest that tests based on the functional properties of one or the other would provide optimal assessment of glaucoma.

Animals↗

The degree of image degradation and the depth of amblyopia.

PURPOSE: To determine whether the depth of monocular form-deprivation amblyopia is dependent on the degree of retinal image degradation. METHODS: Chronic monocular form deprivation was produced in nine infant rhesus monkeys by securing one of three different strengths of diffuser spectacle lenses in front of the treated eye and a clear zero-powered lens in front of the fellow eye. Three infant monkeys reared with plano lenses in front of both eyes provided control data. The treatment lenses were worn continuously from approximately 3 weeks of age for periods ranging between 11 and 19 weeks. When the monkeys were approximately 18 months of age, psychophysical procedures were used to measure the effects of the rearing procedures on the spatial contrast sensitivity function for each eye. RESULTS: The treated eyes of all nine diffuser-reared monkeys showed contrast sensitivity deficits that were indicative of amblyopia. On average, the interocular grating acuity difference increased systematically from 0.6 octaves for the weakest diffuser lens to 2.3 +/- 0.7 and 3.5 +/- 0.8 octaves for the intermediate and strongest diffuser lenses, respectively. There was a close correspondence between the magnitude of the amblyopic deficits and the reduction in retinal image contrast produced by the diffuser lenses. CONCLUSIONS: The results demonstrate that the depth of monocular, nonstrabismic amblyopia is strongly influenced by the degree of retinal image degradation experienced early in life.

Amblyopia↗

Binocular cross-orientation suppression in the primary visual cortex (V1) of infant rhesus monkeys.

PURPOSE: To better understand the course of cortical maturation during early development, the phenomenon of binocular cross-orientation suppression in neurons of the primary visual cortex (V1) in young infant monkeys was investigated. METHODS: Extracellular single-unit recordings were made in anesthetized and paralyzed monkeys ranging in age between 6 days and 8 weeks. Orthogonally oriented, dichoptic sine-wave gratings were used as visual stimuli. RESULTS: V1 neurons in young infant monkeys showed a higher prevalence and greater magnitude of binocular cross-orientation suppression than in adult monkeys. Binocular suppression decreased and reached an adult level between 4 and 8 weeks of age, the presumed onset-age for stereopsis in monkeys. CONCLUSIONS: During the first 4 weeks of life, the functional connections that are necessary for initiating binocular cross-orientation suppression exist in the monkey primary visual cortex. This finding is consistent with the view that before the abrupt onset of stereopsis, human infants may detect the differences between interocularly iso-oriented gratings and orthogonal gratings.

Aging↗

The role of optical defocus in regulating refractive development in infant monkeys.

Early in life, the two eyes of infant primates normally grow in a coordinated manner toward the ideal refractive state. We investigated the extent to which lens-induced changes in the effective focus of the eye affected refractive development in infant rhesus monkeys. The main finding was that spectacle lenses could predictably alter the growth of one or both eyes resulting in appropriate compensating refractive changes in both the hyperopic and myopic directions. Although the effective operating range of the emmetropization process in young monkeys is somewhat limited, the results demonstrate that emmetropization in this higher primate, as in a number of other species, is an active process that is regulated by optical defocus associated with the eye's effective refractive state.

Animals↗

Form deprivation myopia in adolescent monkeys.

BACKGROUND: Early in life, at ages corresponding to the rapid infantile phase of ocular growth in humans, visual feedback can modulate refractive development in monkeys and many other species. To determine if vision-dependent mechanisms can still influence refractive development in primates during the slow juvenile phase of ocular growth, the time period when myopia typically develops in human children, we examined the effects of form deprivation on adolescent monkeys. METHODS: Unilateral, form deprivation was produced in four rhesus monkeys by surgically fusing the eyelids of one eye. The onset of deprivation was between 3.7 and 5 years of age, which corresponds to onset ages between approximately 15 and 20 human years. The ocular effects of form deprivation were assessed by cycloplegic retinoscopy and A-scan ultrasonography. RESULTS: At the onset of form deprivation all four monkeys were isometropic and the axial dimensions in the two eyes were well matched. After 71 to 80 weeks of form deprivation, all of the deprived eyes had become relatively more myopic than their fellow non-treated eyes (mean anisometropia = -2.03 +/- 0.78 D) and they exhibited relative increases in vitreous chamber depth (mean = 0.55 +/- 0.31 mm) and axial length (mean = 0.49 +/- 0.35 mm). DISCUSSION: Our results demonstrate that vision-dependent mechanisms can influence ocular growth and refractive development in "teenage" monkeys. These results raise the possibility that visual experience may be involved in the genesis of school-age myopia in children.

Aging↗

Progressive visual field defects from experimental glaucoma: measurements with white and colored stimuli.

PURPOSE: Our purpose was to study the effects of using monochromatic test stimuli to measure the relative rate of progression of visual field defects caused by experimental glaucoma. METHODS: Visual field measurements were obtained by static perimetry from trained macaque monkeys with laser-induced, unilateral glaucoma. The visual field defects were assessed by perimetric (global) indices derived from comparisons of experimental visual fields to the expected normal fields of monkeys. Three types of perimetry stimuli were used, the conventional white Goldmann III and two monochromatic (460 and 620 nm) Goldmann V test stimuli. The relationships between field defects with white and monochromatic stimuli were investigated by linear regression of the Z-scores for the perimetric indices. RESULTS: The correlations between the mean deviation global indices for chromatic vs. white stimuli were high (r > 0.9) and linear throughout the period of progression of field defects. The slopes of the regression lines typically were greater than unity, indicating that statistical significance was higher for visual field defects measured with chromatic stimuli than with white light stimuli. The higher significance level for defects measured with chromatic stimuli was not explained by a difference in visual thresholds, because the thresholds with chromatic and white light were highly correlated across the full range of visual field defects, from initial-onset to end-state. This result also suggests that the early detection of glaucomatous visual defects with monochromatic stimuli does not reflect a selective loss of retinal ganglion cells. CONCLUSIONS: Although these experiments do not suggest an alternative neural mechanism for the clinical utility of perimetry with chromatic light for the early detection of glaucoma, it is very likely that the combinations of neural and/or analytical factors that explain the utility of perimetry with chromatic stimuli will also provide an explanation for the higher sensitivities in identifying early glaucoma reported for other prototype stimuli.

Animals↗

The American College of Rheumatology criteria for the classification of systemic lupus erythematosus: strengths, weaknesses, and opportunities for improvement.

The American College of Rheumatology classification criteria were developed to operationalize the definition of systemic lupus erythematosus (SLE) to allow comparison of clinical research from different centers, but also serve to facilitate education and to guide clinical practice. The classification criteria have been critical to research, but should be viewed as a temporary step until improved understanding of the pathogenesis of SLE emerges. Criteria have inherent limitations, including bias towards more severe and longer duration disease, equal weighting of features that vary in clinical significance, and exclusion of patients with SLE from research because they do not meet criteria. For some SLE research questions, it may be appropriate to include patients diagnosed with SLE who do not meet criteria, if these patients' manifestations and criteria are documented explicitly. SLE disease activity, cumulative organ damage, disease duration, criteria ever met, and criteria met at time of enrollment are important data that should be presented in clinical studies of SLE regardless of the number of criteria met. The criteria should be reevaluated periodically, utilizing patients and controls with a range of diseases and disease severity. A simplified weighting system may more accurately reflect clinical practice.

Diagnosis, Differential↗

The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma.

PURPOSE: To investigate the photopic flash electroretinograms (ERGs) of macaque monkeys in which visual field defects developed as a consequence of experimental glaucoma. METHODS: Unilateral experimental glaucoma was induced in 10 monkeys by argon laser treatment of the trabecular meshwork. Visual field sensitivity was assessed behaviorally by static perimetry. Photopic ERGs were recorded to brief- (< or = 5 msec) and long-duration (200 msec) red ganzfeld flashes on a rod-suppressing blue-adapting background. Electroretinograms were recorded in four other monkeys, after intravitreal injection of tetrodotoxin (TTX; 3.8-8 p.M) to suppress action potentials of retinal ganglion and amacrine cells, and in six normal adult human subjects. RESULTS: Experimental glaucoma removed a cornea-negative response, the photopic-negative response (PhNR), from the ERG. The PhNR in control eyes was maximal approximately 60 msec after a brief flash, 100 msec after onset, and 115 msec after offset of the long-duration stimulus. The PhNR in experimental eyes was greatly reduced when the mean deviation of the visual field sensitivity was as little as -6 dB. As visual sensitivity declined further, the PhNR was reduced only slightly more. The a- and b-waves were unchanged, even when sensitivity decreased by more than 16 dB. Tetrodotoxin also selectively reduced the PhNR. The PhNR was observed in normal human ERGs. CONCLUSIONS: The cornea-negative PhNR of the photopic ERG depends on spiking activity and is reduced in experimental glaucoma when visual sensitivity losses are still mild. The PhNR most likely arises from retinal ganglion cells and their axons, but its slow timing raises the possibility that it could be mediated by glia. Regardless of the mechanism of its generation, the PhNR holds promise as an indicator of retinal function in early glaucomatous optic neuropathy.

Adult↗

Ganglion cell losses underlying visual field defects from experimental glaucoma.

PURPOSE: To investigate the relationship between ganglion cell losses and visual field defects caused by glaucoma. METHODS: Behavioral perimetry and histology data were obtained from 10 rhesus monkeys with unilateral experimental glaucoma that was induced by argon laser treatments to their trabecular meshwork. After significant visual field defects had developed, the retinas were collected for histologic analysis. The ganglion cells were counted by light microscopy in cresyl violet-stained retina sections, and the percentage of ganglion cell loss (treated to control eye counts) was compared with the depth of visual field defect (treated to control eye thresholds) at corresponding retinal and perimetry test locations. Sensitivity losses as a function of ganglion cell losses were analyzed for Goldmann III, white and Goldmann V, and short- and long-wavelength perimetry test stimuli. RESULTS: The relationship between the proportional losses of ganglion cells and visual sensitivity, measured with either white or colored stimuli, was nonlinear. With white stimuli, the visual sensitivity losses were relatively constant (approximately 6 dB) for ganglion cell losses of less than 30% to 50%, and then with greater amounts of cell loss the visual defects were more systematically related to ganglion cell loss (approximately 0.42 dB/percent cell loss). The forms of the neural-sensitivity relationships for visual defects measured with short- or long-wavelength perimetry stimuli were similar when the visual thresholds were normalized to compensate for differences in expected normal thresholds for white and colored perimetry stimuli. CONCLUSIONS: Current perimetry regimens with either white or monochromatic stimuli do not provide a useful estimate of ganglion cell loss until a substantial proportion have died. The variance in ganglion cell loss is large for mild defects that would be diagnostic of early glaucoma and for visual field locations near the fovea where sensitivity losses occur relatively late in the disease process. The neural-sensitivity relationships were essentially identical for both white and monochromatic test stimuli, and it therefore seems unlikely that the higher sensitivity for detecting glaucoma with monochromatic stimuli is based on the size-dependent susceptibility of ganglion cells to injury from glaucoma.

Animals↗

Developmental visual system anomalies and the limits of emmetropization.

Optical defocus can within certain limits predictably alter ocular growth and refractive development in infant monkeys. However defocus, particularly unilateral defocus associated with anisometropia, can also promote abnormal sensory and motor development. We investigated the relationship between the effective operating range for emmetropization in infant monkeys and the refractive errors that produced amblyopia. Specifically, we examined the refractive-error histories of monkeys that did not demonstrate compensating ocular growth for imposed refractive errors and used operant psychophysical methods to measure contrast sensitivity functions for 17 infant monkeys that were reared with varying degrees of optically imposed anisometropia. Imposed anisometropias that were within the operating range of the monkey's emmetropization process were eliminated by differential interocular growth and did not produce amblyopia. On the other hand imposed anisometropias that failed to initiate compensating growth consistently produced amblyopia; the depth of the amblyopia varied directly with the magnitude of the imposed anisometropia. These results indicate that amblyopia and anisometropia are frequently associated because persistent anisometropia causes amblyopia. However, the failure of emmetropization in infants with refractive conditions that are known to promote sensory and motor anomalies indicates that factors other than optical defocus, presumably factors associated with the development of amblyopia and/or strabismus, can also influence early refractive development and in some cases cause anisometropia.

Amblyopia↗

Acute effects of interleukin-1 beta on noradrenaline release from the human neuroblastoma cell line SH-SY5Y.

Interleukins are potent intercellular messenger peptides, initially found in cells of the immune system and best known for producing chronic, genomic effects in target cells. Here, interleukin-1beta (IL-1beta) was tested for acute effects on neurotransmitter release. The human neuroblastoma-derived cell-line SH-SY5Y is a model for mature post-ganglionic sympathetic neurones and release of tritiated noradrenaline from these cells was measured, in response to stimulation with either elevated extracellular K+ concentration (100 K+) orveratridine. Pre-incubation for 15-25 min with 60 pM (but not 0.06 pM) IL-1beta significantly reduced 100 K+-evoked release (by approximately 75%). The interleukin was without effect on basal or veratridine-evoked noradrenaline release. The present data suggest two distinct stimulatory pathways: one that is activated by 100 K+ and veratridine and is unaffected by IL-1beta and another that is activated by 100 K+ but not veratridine and is inhibited by IL-1beta. The acute depression of 100 K+-evoked transmitter release may be involved in immune system-nervous system interactions.

Humans↗

Glutamine immunoreactivity in Müller cells of monkey eyes with experimental glaucoma.

The action of glutamate in retina is largely terminated through rapid uptake by Müller cells and subsequent conversion primarily to glutamine. Glutamine, transferred from Müller cells to neurons, serves as a precursor for the formation of glutamate in neurons completing the glutamate-glutamine cycle. In a monkey model of high-tension glaucoma, we have examined glutamine immunoreactivity in the Müller cell as well as the number of Müller cells to determine whether the activity of these cells in the glutamate-glutamine cycle is affected, particularly since high vitreal glutamate has been reported in glaucoma. Unilateral glaucoma was induced in three monkeys by argon laser application to the trabecular meshwork. LR White sections of retina from the temporal mid-periphery (about 23 degrees) and the parafovea (central 3 degrees) were immunolabeled for glutamine using immunogold and silver intensification. The percentage difference in labeling intensity (darkness) in the glaucomatous retina was determined relative to the labeling found in the control retina by image analysis. Ganglion cell density was estimated from radial sections in the parafovea and from retinal whole mounts in the mid-periphery. The number of Müller cells was estimated from vibratome sections immunolabeled by vimentin antibodies in the temporal mid-periphery (about 30 degrees). Glutamine immunoreactivity was localized predominately in ganglion cells and Müller cells. However, the intensity of glutamine immunolabeling was greater in Müller cells of glaucomatous eyes than in control eyes. This increase in glutamine immunolabeling was 25-32% in the temporal mid-periphery and 27-48% in the parafovea. Müller cell number in the glaucomatous eye was similar to that of the control in the temporal mid-periphery. The data in this study indicate that the increase in glutamine in Müller cells is not a consequence of their loss and that Müller cell function in the glutamate-glutamine cycle continues in glaucomatous eyes. These findings are consistent with a previous report that extracellular/vitreal glutamate concentration is elevated in high-tension glaucoma.

Animals↗

Effects of early discordant binocular vision on the postnatal development of parvocellular neurons in the monkey lateral geniculate nucleus.

The effects of early discordant binocular vision on the fidelity of signal transfer in parvocellular neurons of the lateral geniculate nucleus (LGN) were investigated in rhesus monkeys reared with ocular misalignment (strabismus). Unilateral convergent strabismus (esotropia) was surgically induced in four infant monkeys between 20 and 30 days of age and the animals were reared in a normally lighted environment until they were adults. Extracellular microelectrode recordings were made in individual units of anesthetized and paralyzed subjects. Drifting sinusoidal gratings were used as visual stimuli. Within-unit comparisons of the LGN action potentials (LGN output) and S potentials (retinal input) were performed to determine the accuracy of signal transfer in the LGN. Contrary to the previous findings in the cat LGN, the signal transfer characteristics of parvocellular units in strabismic monkeys were normal regardless of stimulus spatial frequency, temporal frequency, or contrast. The differences between cats and monkeys in LGN circuitry and the relative maturity of the central visual pathway at the onset of strabismus may have contributed to the apparent species differences in the functional development of the LGN.

Action Potentials↗

Pulmonary metastasis.

OBJECTIVES: To provide a review of pulmonary-specific pathophysiology and pulmonary metastasis-related information regarding diagnostic tests, differential diagnoses, signs and symptoms, treatment, and nursing implications. DATA SOURCES: Research studies, review papers, and case reports pertaining to pulmonary metastasis. CONCLUSIONS: Several site-specific mechanisms of metastasis may begin to explain why the lungs are a common metastatic site. There are circumstances when pulmonary metastases can be either surgically removed or treated with combined modalities, resulting in prolonged survival. IMPLICATIONS FOR NURSING PRACTICE: Metastatic disease may be treated aggressively; for some patients, this can result in prolonged survival while maintaining reasonable quality of life. A useful basic resource for obtaining a pulmonary history is provided. Key points regarding symptom management and patient education also are discussed.

Humans↗

Spectacle lenses and emmetropization: the role of optical defocus in regulating ocular development.

The purpose of our investigation was to determine whether early ocular growth and refractive development was regulated by visual feedback in infant monkeys. Specifically, we examined the ability of infant monkeys to compensate for optically induced changes in the eye's refractive state and to recover from experimentally induced refractive errors. For moderate-powered anisometropic lenses, infants exhibited differential interocular axial growth rates that reduced the lens-induced refractive imbalance between the two eyes. Infants treated with equal-powered lenses over both eyes also showed compensating growth. For lens powers between approximately -3 and +6 D, the resulting refractive-error changes, which were primarily due to alterations in vitreous chamber growth rates, were well correlated with the effective refractive state produced by the treatment lenses. When the stimulus for altered eye growth was removed and the infants were provided unrestricted vision, monkey eyes consistently grew toward emmetropia. The remarkable degree of adaptability exhibited by the eyes of infant monkeys demonstrates that emmetropization in this higher primate is an active process that is regulated on a continuous basis by optical defocus. Consequently, early in life spectacle lenses by changing the eye's effective focus can predictably alter ocular growth and the refractive status of one or both eyes.

Animals↗