Right hemisphere dysfunction: therapeutic intervention from acute care to home health.

This article discusses clinical practice variances in speech-language treatment of patients with right hemisphere dysfunction by therapeutic milieu. With an eye toward enhanced cost effectiveness, a model of intervention is presented that takes a patient from acute care management through rehabilitation. Issues discussed include assessment, family training, goal setting, and documentation. A right hemisphere screening tool is included in an appendix for use in acute and transitional care settings where in-depth testing might be inappropriate because of time constraints or the acute or transitory nature of the patient's symptoms.

Use of the family to facilitate communicative changes in adults with neurological impairments.

Systemic concepts may be used to expand upon the traditional notion that family members influence the outcome of treatment services to adults with neurological communicative disorders. Several systemic concepts are discussed and illustrated as they are used with different clients having (1) aphasia, (2) right cerebral hemisphere dysfunction, and (3) progressive dementia. Discussion focuses on determining the unit of treatment with which to work, promoting and measuring positive communicative changes, and selecting effective intervention techniques.

Primate rod and cone photoreceptors may differ in glucose accessibility.

PURPOSE: Glucose is crucial for the function of retinal photoreceptors, other retinal neurons, and glial cells. Exogenous glucose can be extracted from the retinal and choroidal circulation, and endogenous glucose may be generated from breakdown of intracellular glycogen stores. Because glucose deprivation is a critical component of retinal ischemia, the authors sought to determine the sites of glucose entry into and generation within the retina. METHODS: The localization of the glucose transporter, GluT-1, and the brain and muscle isozymes of glycogen phosphorylase, GlyP, was studied by immunohistochemistry of adult human and monkey retinas. RESULTS: Brain glycogen phosphorylase (B-GlyP) immunoreactivity was found in cone, but not rod, photoreceptors. There was immunostaining of foveal and peripheral cones throughout the cytoplasm from the outer segment to the synaptic pedicle. Short wavelength ("blue") cones were positive for B-GlyP. Diffuse staining of the inner and outer plexiform and the nerve fiber layers did not resemble the distinct morphology of Müller cells. Immunoreactivity to muscle GlyP (M-GlyP) was confined to selected synaptic layers of the inner plexiform layer in monkey retina. Staining with antibody to GluT-1 demonstrated diffuse reactivity throughout the retina, including the blood-retinal barrier cells, retinal pigment epithelium, and vascular endothelium. Ultrastructural immunohistochemistry showed staining of rod and cone inner and outer segments. CONCLUSIONS: These immunohistochemical studies indicate that rod and cone photoreceptors have the biochemical capability to transport exogenous glucose from the circulation. Only cones appear capable of using endogenous glycogen stores. These findings imply that cones could be more resistant to acute reductions in circulating glucose during hypoglycemia. However, during hypoxic insult, glycogenolysis and anaerobic glycolysis could result in increased production of intracellular lactic acid, potentially predisposing the cone to acidotic damage.

The retinal pigment epithelium induces fenestration of endothelial cells in vivo.

Rodent photoreceptor dystrophies are characterized by late stage ingrowth of retinal blood vessels into the retinal pigment epithelium (RPE) where they proliferate. Some of these vessels develop the fenestrated phenotype of the choriocapillaris (CC). To determine if development of fenestrae in these endothelial cells is a function of the duration of time the endothelial cell had been encapsulated by the RPE, we did an ultrastructural morphometric study of these vessels in urethane induced photoreceptor degeneration in Long-Evans rats. Retinas of animals aged 20, 24, 40 and 56 weeks were studied. The fraction of vessel profiles within the RPE that had fenestrated endothelial cells increased from 10% to 90% between 20 to 56 weeks. The average number of fenestrae per vessel increased approximately 25 fold between 20 and 24 weeks but stabilized after that, despite a decrease in the number of vessels present at 56 weeks. A large number of degenerated retinal vessel profiles were seen in the RPE at 40 weeks. These facts support the idea that the presence of the RPE induces endothelial cell fenestrae, and also show that a complex process of remodelling including proliferation and degeneration is occurring in these vessels. Analogies between the basic cell biology of neovascularization occurring in these rodent models and that of proliferative diabetic retinopathy and age-related macular degeneration are discussed.

An experimental model of ectropion uveae and iris neovascularization in the cat.

Neovascularization of the iris (NVI) is one of the most frequently studied intraocular vascular proliferations in animal models. Ectropion uveae has not been a consistent finding in these studies. In this study, a surgical model of ectropion uveae and iris neovascularization was developed that involved lensectomy, vitrectomy, bipolar cautery and transection of all three principal branch veins in the cat eye. Twelve of 14 eyes that received this procedure developed postoperative retinal detachments with a clinical picture of hemorrhagic retinopathy. These eyes progressed to a clinical picture of NVI within 1-7 wk. Eight eyes developed ectropion uveae for as much as 300 degrees. At the light microscopic level, a fibrovascular membrane was apparent on the anterior iris stroma in 9 of 14 eyes and further involved the angle in six eyes.

Comparison of lectin reactivity in the vessel beds of the rat eye.

The capillary beds of the eye are lined by two types of endothelia, fenestrated in the choriocapillaris and ciliary body, and continuous in the retina and iris. In this study, we wished to find a marker for each of these types of vessel beds using lectin histochemistry. Sections of glutaraldehyde fixed rat eyes embedded in epoxy resin were extracted with sodium ethoxide and rehydrated. Binding of 15 different lectins was visualized using the avidin-biotin peroxidase technique. We found WGA, WGA-s, LFA and PHA-E to strongly bind retinal vessels. In addition to the above lectins, iris vessels bound GSL-I. Choriocapillaris reacted variably only with WGA and not at all with other lectins tested. Vessels of ciliary body processes did not react with any lectin studied. The less fenestrated vessels of the base of the ciliary process bound lectins similar to the retina. We speculate that the differential lectin staining of the various vessel beds of the eye may reflect the degree of fenestration of the endothelium. This reactivity may be influenced by variations in the surrounding milieu including cells and extracellular matrix.

Alterations in glial cell morphology and glial fibrillary acidic protein expression in urethane-induced retinopathy.

Urethane injection in newborn rats causes a photoreceptor degeneration without initial damage to the retinal pigment epithelium, choriocapillaris, or inner retina. In later stages, retinal vessels become incorporated into the retinal pigment epithelium (RPE) and change from a continuous endothelial cell phenotype to a fenestrated phenotype. At the light-microscopic level, there do not appear to be morphologic changes in the inner retina up to 24 weeks of age. Ultrastructurally, however, there are alterations in Müller cell cytotopographic organization. In the normal retina, intermediate filaments are primarily found from the ganglion cell layer to the inner nuclear layer. These filaments do not show glial fibrillary acidic protein immunoreactivity (GFAP-IR) in the normal animal. In the urethane-treated animals, the compartmental organization of the Müller cell organelles is moved vitread. Intermediate filaments are found in the end-foot region, and in the inner plexiform layer, bundles of intermediate filaments become more prominent. All of these filaments are GFAP-IR positive. The new expression of GFAP in the Müller cell may be linked to the observed rearrangement of the cytoskeletal elements. In urethane-induced retinopathy, GFAP-IR is found associated with vessels in all layers of the remaining retina. However, it is not seen accompanying vessels into the RPE. Ultrastructurally, there is no glial investment of the RPE-associated vessels. This absence of glial investment may permit the change in phenotype observed in these vessels.

Selective neovascularization of the retinal pigment epithelium in rat photoreceptor degeneration in vivo.

Photoreceptor cell degeneration in rodents from a variety of causes results in neovascularization of the retinal pigment epithelium as a late stage phenomenon. Even though the vessels within the pigment epithelium arise from the retinal circulation, they can manifest the choroidal endothelial cell phenotype of fenestrated endothelial cells. In order to study the detailed cellular events which result in incorporation of retinal vessels within the retinal pigment epithelium, a morphological and morphometric analysis of the RPE and vasculature was performed in rats. Urethane, given subcutaneously to newborn rats, results in a photoreceptor degeneration but does not affect the RPE, choroid or inner retinal layers. Retinas were studied from rats of 8 to 24 weeks of age, the time period when vascularization of the RPE occurs. Loss of retinal vessels is first seen at 12 weeks, primarily in substantial dropout of vessel profiles in the outer plexiform layer (OPL) vessel bed. There is a gradient of loss from the OPL bed to the nerve fiber layer (NFL) bed and from the central to peripheral region. Total vessel density of the experimental retinas is greater than controls at 8 and 12 weeks. This occurs because there is marked loss of retinal thickness, due to photoreceptor degeneration, without a comparable loss of vessel profiles. The total retinal vessel density decreases from 8 to 20 weeks, and appears to stabilize at 20 and 24 weeks. Analysis of the separate vessel beds shows that this apparent stabilization is due to continued loss of vessels within the sensory retina, and increased presence of vascular profiles within the RPE. Total absence of the photoreceptor cell is necessary for incorporation of vessels within the RPE. Since new vessel profiles develop in the RPE but not the adjacent sensory retina, we speculate that the RPE may stimulate neovascularization of the RPE. A model of the cellular events leading to RPE neovascularization is proposed.

Interglial cell gap junctions increase in urethane-induced photoreceptor degeneration in rats.

Gap junctions are found between astrocytes in the inner retina of normal rats, but they are rare between Müller cells or between astrocytes and Müller cells in the inner retina. After photoreceptor degeneration induced by urethane treatment of newborn animals, morphologic alterations of glial cells occur in the inner retina. The Müller cells withdraw from the inner limiting membrane, and the astrocytes hypertrophy and occupy the vitread surface of the inner limiting membrane. The frequency and size of the gap junctions between astrocytes increases with time in rats with urethane-induced photoreceptor degeneration, to a greater extent than expected from elaboration of additional astrocyte plasma membrane. The gap junction-profile length per glial cell membrane-contact length is 2.8 +/- 1.1 microns/1000 microns of membrane in 8-week-old normal animals; it increases to 18.9 +/- 9.4 microns/1000 microns of membrane at 56 weeks of age in urethane-treated animals. The average size of the gap junction-profile length doubles during this same period. To the authors' knowledge this is the first study demonstrating pathologic changes in gap junctions in central nervous system tissue. The authors speculate that this up-regulation of gap junctions occurs in response to an altered extracellular ionic composition in an attempt to increase the lateral spatial buffering of K+ by these cells. The relative location of glial cells in retina can determine, in part, the vulnerability of the retina to edema.

Müller cell GFAP expression exhibits gradient from focus of photoreceptor light damage.

High intensity (ca. 150 foot-candles), cumulative fluorescent light exposure regimes of 40 or 60 minutes to pigmented Long Evans rats were sufficient to elicit glial fibrillary acidic protein immunoreactivity (GFAP-IR) in Müller cells, when the animals are sacrificed 7 days post-exposure. Exposure to only 20 minutes of cumulative light or sacrifice immediately after exposure was not sufficient to initiate GFAP-IR in Müller cells. A gradient of GFAP-IR was observed extending from an approximately circular focus superior to the optic disc to the peripheral retina, whether or not there was morphological damage to the photoreceptors observable at the light microscopic level. Photoreceptor lesions produced by laser photocoagulation elicited the same gradient of GFAP-IR, and showed that GFAP-IR was not a reflection of a central to peripheral gradient of light received by the retina. Excessive light exposure initiated a signal which induced GFAP expression in Müller cells. This signal appeared to require a dark period and may be a diffusible factor that moves through extracellular pathways.

Refractive state, ocular anatomy, and accommodative range of the sea otter (Enhydra lutris).

Sea otters are carnivorous, amphibious mammals that are active both above and under water. Accordingly, it might be expected that their eyes are adapted for both aerial and aqueous vision. We examined the anatomy and physiological optics of the sea otter eye with a view towards describing and explaining its amphibious visual characteristics. We employed photokeratoscopy to measure the refractive power of the sea otter cornea, which we found to be 59 D. Using video dynamic photorefraction, we found that sea otters can focus targets clearly both in air and water, relying on accommodation to compensate for the refractive loss of their corneas upon immersion in water. Our anatomical investigations revealed that the anterior epithelium of the cornea is extensively developed, as is the iris musculature, meridional ciliary muscle, and the corneoscleral venous plexus. The first feature is most likely an adaptation to the salinity of the marine environment. We believe the latter features are part of a novel, well-developed lenticular accommodative mechanism.

Melanosome abnormalities of ocular pigmented epithelial cells in beagle dogs with hereditary tapetal degeneration.

Eyes of laboratory beagle dogs with an inherited tapetal degeneration were abnormally lightly pigmented. The development of pigmentation was followed morphologically from 7 days postnatal to 9 years of age. At all postnatal ages the iris pigmented epithelia contained no normal melanosomes, only organelles resembling secondary lysosomes or residual bodies. The ciliary body pigmented epithelium contained a variety of melanosome organelles at the earliest stages examined, but in fewer numbers than in normal animals. These included premelanosomes, partially melanized and some fully melanized pigment granules. However, the melanin deposition was usually patchy and irregular. With time, many of these granules appeared to condense into residual bodies. The retinal pigmented epithelium in peripheral and inferior posterior regions of affected animals never contained normal appearing melanin granules at any stage of postnatal development. The iris and choroidal stroma had melanosomes of normal size and shape, but many fewer than in normal animals. These results imply that there is local cellular control over melanosome production and regression, since the melanosome abnormalities do not follow the anterior to posterior development of pigment in ocular epithelia. It is proposed that a defect in synthesis of the matrix component of melanosomes could result in absent or abnormal deposition of melanin and initiate a process of autophagy of these organelles.

Development of hereditary tapetal degeneration in the beagle dog.

Laboratory beagle dogs with an apparent absence of a tapetum lucidum were identified by ophthalmoscopic examination. Breeding experiments demonstrated a probable autosomal recessive mutation. Studies of the development of the tapetal abnormality showed that up to postnatal day 21 the tapetum was normal by light and ultrastructural morphology. Subsequent to that time the tapetal rodlets failed to accumulate electron-dense material, did not accumulate zinc, and degenerated primarily into spherical inclusion bodies of varying electron density. In the early phases of the degeneration the rough endoplasmic reticulum formed large whorls of membrane denuded of ribosomes. With time, the inclusions became electron lucent, and the entire tapetal cell degenerated, ending with almost total loss of the tapetum lucidum by approximately one to two years of age. The structure of the retina was normal. Retinal function measured by electroretinography was normal except for a slight elevation of dark adapted white light thresholds. It is speculated that the hereditary defect may be defective synthesis of the tapetal rodlet matrix or of the zinc-complexing substance of the tapetum.

Biological microanalysis by secondary ion mass spectrometry: status and prospects.

Secondary ion mass spectrometric (SIMS) analysis of biological problems is an evolving technique. Lateral resolution of currently available commercial instrumentation estimated from actual samples is 0.5 micron, and subcellular organelles can be distinguished. The interrelationship of lateral resolution, elemental concentration and ionizability are, however, important in controlling the actual lateral resolution achievable. Although depth resolutions of 5 nm have been measured in other systems, no test of depth resolution in biological systems has been done, and this parameter is also concentration and ionization dependent. The development of liquid metal ion sources in combination with scanning ion microprobes has a potential lateral resolution of as little as 20 nm, but initial studies with this instrumentation show that tissue preservation at the submicron level becomes an important issue. The current development of a cold-transfer stage for SIMS instruments may obviate the problem of submicron localization of diffusible elements, and initial studies indicate that much more needs to be understood about the ionization process in hydrated samples. Quantitation of diffusible elements using external standards has been achieved over a 30 micron diameter analyzed area. Strategies for analysis of areas limited to 1 micron or less has been suggested using image processing techniques, which take advantage of the lateral resolution inherent in the ion optical system. Matrix effects in biological tissues have been reported and constitute a serious problem for analysis of biologicals which must be addressed for each question. However, development of laser ionization of sputtered particles may both increase the sensitivity of analysis and decrease the importance of ionizability of elements. Chemical analysis of organic molecules is another use of SIMS, but, at present, at the cost of losing localized information. SIMS analysis of biological samples is being systematically evaluated and requires increased accessibility of this instrumentation to the end-user for full development of its role in physiological problems.

Retinal degeneration in the WKY rat.

An outer retinal degeneration occurs in middle aged Wistar-Kyoto (WKY) rats, the normotensive counterpart to the spontaneous hypertensive rat strain (SHR). The degeneration, like that of other spontaneous and experimentally-induced outer layer retinopathies of rats, is characterized by a progressive loss of photoreceptor and outer nuclear layers which, in turn, leads to contact between the deep capillary bed of the retina and the retinal pigment epithelial (RPE) cells. RPE proliferation and/or migration causes a number of capillaries to become enmeshed within RPE cells, and some of those capillaries undergo morphologic and physiologic alterations such that they resemble choroidal capillaries. There is variable loss of the choriocapillaris associated with this retinopathy, but since this is also seen to some degree in normal eyes, it is not known if this is an integral part of the pathologic process.

Quantitative microlocalization of diffusible ions in normal and galactose cataractous rat lens by secondary ion mass spectrometry.

Secondary ion mass spectrometry (SIMS) is a surface analytical technique with high sensitivity for elemental detection and microlocalization capabilities within the micrometre range. Quantitative analysis of epoxy resins and gelatin have been reported (Burns-Bellhorn & File, 1979). We report here the first application of this technique to quantitative microlocalization in the context of a physiological problem--analyses of sodium, potassium and calcium in normal and galactose-induced cataract in rat lens. It is known that during the development of galactose-induced cataract the whole lens content of potassium is decreased, sodium is increased and, in late stages, calcium concentration increases. Whether these alterations in diffusible ions occur homogeneously or heterogeneously is not known. Standard curves were generated from epoxy resins containing known concentrations of sodium, potassium or calcium organometallic compounds using the Cameca IMS 300 Secondary Ion Mass Spectrometer. Normal and cataractous lenses were prepared by freezing in isopentane in a liquid nitrogen bath followed by freeze-drying at -30 degrees C. After dry embedding in epoxy resin, 10 microns thick sections of lens were pressure mounted on silicon wafers, overcoated with gold, and ion emission measured under the same instrumental conditions used to obtain the standard curves. Quantitative analysis of an area 27 microns in diameter, or a total analysed volume of 1.1 microns3, was performed by using a mechanical aperture in the ion optical system. Ion images provided qualitative microanalysis with a lateral resolution of 1 micron. Control rat lenses gave values for sodium and potassium content with a precision of +/- 17% or less. These values were compared to flame photometry and atomic absorption measurements of normal lenses and were accurate within 25%. Analysis of serum and blood also gave accurate and precise measurements of these elements. Normal rat lenses had a gradient of sodium, and, to a lesser degree, of potassium from the cortex to the nucleus. Development of galactose-induced cataract was heterogeneous by morphological criteria, beginning at the lens equator and spreading from the cortex into the nucleus. However, the loss of potassium and increase in sodium concentration occurred at early stages in both the cortex and nucleus cells, possibly because these cells are interconnected by gap junctions. There is a local alteration in elemental content prior to morphologically demonstrable cataract formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Neovascularization in urethane rat retinopathy demonstrated by thymidine labelling.

Rat urethane retinopathy produces sequential and progressive loss of the photoreceptor cells, proceeding from the posterior to the peripheral retina. The inner retina, the retinal pigment epithelium and the choriocapillaris are spared. After loss of the photoreceptor cells, a vasculopathy develops which includes progressive retinal capillary loss and formation of coil-like tufts of retinal vessels which are embedded in the retinal pigment epithelium. Some of the retinal vessels within the retinal pigment epithelium have changed their phenotype from continuous to fenestrated endothelial cells. To elucidate whether DNA synthesis was necessary for formation of the coil-like vessel tuft formation, an autoradiographic study was performed. At 12, 14, 16 and 20 weeks of age, times during which the vasculopathy is known to be forming, urethane and control rats were injected with 3 successive doses of methyl-3H-thymidine. Autoradiography of trypsin-digested retinal vessel preparations was compared with histological sections of the paired eye. The frequency of tritium labelled endothelial cells was much higher in the urethane rats than control animals, and were predominantly in the posterior pole, rather than the periphery. Labelled endothelial cells tended to be associated with, or near, the coil-like vessel tufts. Capillary dropout was observed in urethane, but not control animals. Frequently, adjacent endothelial cells were labelled, suggestive of mitosis. The occurrence of thymidine uptake and a change in phenotype of the endothelial cells leads us to suggest that new cell synthesis, or neovascularization, has occurred in these vessels. Since the retina is less than half the normal thickness and the choriocapillaris is intact, it appears unlikely that ischemia is responsible for inducing these pathological responses. We suggest that the retinal pigment epithelial cell is responsible for the increase in DNA synthesis and change in phenotype of the retinal endothelial cell.