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PubMed2004

Results from screening over 9000 mutation-bearing mice for defects in the electroretinogram and appearance of the fundus.

Random mutagenesis combined with phenotypic screening using carefully crafted functional tests has successfully led to the discovery of genes that are essential for a number of functions. This approach does not require prior knowledge of the identity of the genes that are involved and is a way to ascribe function to the nearly 6000 genes for which knowledge of the DNA sequence has been inadequate to determine the function of the gene product. In an effort to identify genes involved in the visual system via this approach, we have tested over 9000 first and third generation offspring of mice treated with the mutagen N-ethyl-N-nitrosourea (ENU) for visual defects, as evidenced by abnormalities in the electroretinogram and appearance of the fundus. We identified 61 putative mutations with this procedure and outline the steps needed to identify the affected genes.

Animals↗
PubMed1998

Screening for ophthalmic disease in older subjects using visual acuity and contrast sensitivity.

OBJECTIVE: Despite early interest in contrast sensitivity as a screening test for ophthalmic disease, most published opinion suggests that there is no benefit over conventional measurement of visual acuity. Taking a primary care perspective of screening, the authors evaluated the ability to discriminate those with any diagnosed ophthalmic disease in a large sample representative of the general population. DESIGN: Retrospective analysis of a clinical, cross-sectional survey. Snellen visual acuity, contrast sensitivity (Arden plates, American Optical contrast sensitivity test), and ophthalmic diagnosis were reported previously. PARTICIPANTS: A sample of 3283 subjects, all aged at least 50 years, were selected randomly from residents of a health district in Sydney, Australia. Ophthalmologic diagnosis (ophthalmic disease presence/absence) had been confirmed for 2522 of these subjects. MAIN OUTCOME MEASURES: Signal detection techniques (the receiver-operating characteristics function [ROC], quality ROC [QROC], and weighted kappa coefficient of association [kappa(r)]) were used to evaluate test discriminability. RESULTS: Because analyses of right and left eyes were almost identical, only right eye results are presented. Advantages of kappa(r) over ROC were shown. Discrimination of those with diagnosed ophthalmic disease from those without ophthalmic disease was best with Arden plate 7 (kappa0.5 = 0.93) and was better than distance Snellen visual acuity (kappa0.5 = 0.59). Arden plate 7 (6.4 cyc/deg) correctly assigned 96% of subjects at its optimal pass-fail criterion. CONCLUSIONS: In the primary care setting, a person older than 50 years of age with reduced contrast sensitivity, as determined by Arden plate 7, requires extra care in subsequent examinations because this person is likely to have an ophthalmic disease.

Aged↗
PubMed2003

Programme planning and screening strategy in retinopathy of prematurity.

Retinopathy of Prematurity (ROP) is one of the major emerging causes of childhood blindness. A well organised screening strategy and timely intervention can to a large extent prevent blindness due to ROP. This communication proposes a screening strategy and management plan to develop a model for the care of babies with ROP.

Blindness↗
PubMedDate not supplied

Health promotion for the nursing home patient.

BACKGROUND: The current nursing home population numbers at least 1.5 million and is growing. Although care of the nursing home patient has been emphasized recently, health promotion activities for these patients appear underused. Current recommendations for health promotion are based on expert opinion, because well-controlled studies to support such activities in the elderly are lacking for most practices. METHODS: Using the key words "health promotion" and "preventive health services," cross-referenced with "aged," articles were selected from MEDLINE files from 1979 to the present. Bibliographies of these references were reviewed to select additional references. RESULTS: A review of the literature shows that although health promotion activities are not appropriate for every nursing home patient, many patients live for years in the long-term care facility and can benefit from health promotion. Health promotion activities can be organized around patients' length of stay. Procedures that should be considered include breast cancer screening, Papanicolaou smears for cervical cancer, hearing and vision loss screening, fall prevention assessment, immunizations, screening for dementia and depression, drug evaluation, screening for thyroid disease, and advance directives. CONCLUSIONS: Physicians who practice in nursing homes should consider health promotion for select nursing home patients.

Aged↗
PubMed2005

A mutation in the silver gene leads to defects in melanosome biogenesis and alterations in the visual system in the zebrafish mutant fading vision.

Forward genetic screens have been instrumental in defining molecular components of visual function. The zebrafish mutant fading vision (fdv) has been identified in such a screen due to defects in vision accompanied by hypopigmentation in the retinal pigment epithelium (RPE) and body melanocytes. The RPE forms the outer most layer of the retina, and its function is essential for vision. In fdv mutant larvae, the outer segments of photoreceptors are strongly reduced in length or absent due to defects in RPE cells. Ultrastructural analysis of RPE cells reveals dramatic cellular changes such as an absence of microvilli and vesicular inclusions. The retinoid profile is altered as judged by biochemical analysis, arguing for a partial block in visual pigment regeneration. Surprisingly, homozygous fdv vision mutants survive to adulthood and show, despite a persistence of the hypopigmentation, a partial recovery of retinal morphology. By positional cloning and subsequent morpholino knock-down, we identified a mutation in the silver gene as the molecular defect underlying the fdv phenotype. The Silver protein is required for intralumenal fibril formation in melanosomes by amylogenic cleavage. Our data reveal an unexpected link between melanosome biogenesis and the visual system, undetectable in cell culture.

Amino Acid Sequence↗
PubMed2003

Visual acuity, optical, and eye health readiness in the military.

Optimum vision readiness is essential on today's technologically advanced battlefield. A vision readiness screening of 4,825 active duty personnel at 13 Department of Defense sites from September through December 1997 revealed 4,021 (83.3%) not vision ready: 500 (10.4%) had substandard visual acuity, 1,249 (25.9%) had deficient optical devices, and 3,562 (73.8%) had eye health-related deficiencies. This suggests a more effective ongoing vision readiness process should be implemented to ensure all personnel are vision ready prior to deployment.

Contact Lenses↗
PubMed1994

Accuracy of planar reaching movements. I. Independence of direction and extent variability.

This study examined the variability in movement end points in a task in which human subjects reached to targets in different locations on a horizontal surface. The primary purpose was to determine whether patterns in the variable errors would reveal the nature and origin of the coordinate system in which the movements were planned. Six subjects moved a hand-held cursor on a digitizing tablet. Target and cursor positions were displayed on a computer screen, and vision of the hand and arm was blocked. The screen cursor was blanked during movement to prevent visual corrections. The paths of the movements were straight and thus directions were largely specified at the onset of movement. The velocity profiles were bell-shaped, and peak velocities and accelerations were scaled to target distance, implying that movement extent was also programmed in advance of the movement. The spatial distributions of movement end points were elliptical in shape. The major axes of these ellipses were systematically oriented in the direction of hand movement with respect to its initial position. This was true for both fast and slow movements, as well as for pointing movements involving rotations of the wrist joint. Using principal components analysis to compute the axes of these ellipses, we found that the eccentricity of the elliptical dispersions was uniformly greater for small than for large movements: variability along the axis of movement, representing extent variability, increased markedly but nonlinearly with distance. Variability perpendicular to the direction of movement, which results from directional errors, was generally smaller than extent variability, but it increased in proportion to the extent of the movement. Therefore, directional variability, in angular terms, was constant and independent of distance. Because the patterns of variability were similar for both slow and fast movements, as well as for movements involving different joints, we conclude that they result largely from errors in the planning process. We also argue that they cannot be simply explained as consequences of the inertial properties of the limb. Rather they provide evidence for an organizing mechanism that moves the limb along a straight path. We further conclude that reaching movements are planned in a hand-centered coordinate system, with direction and extent of hand movement as the planned parameters. Since the factors which influence directional variability are independent of those that influence extent errors, we propose that these two variables can be separately specified by the brain.

Adult↗
PubMed1992

Cost-effectiveness of the screening and treatment of diabetic retinopathy. What are the costs of underutilization?

Diabetic retinal disease remains a leading cause of visual disability among those of working age. Controlled trials have demonstrated that timely diagnosis and photocoagulation treatment can reduce significantly the likelihood of visual impairment in affected diabetic patients. Using a prospective simulation model, we show that an annual screening and treatment program saves thousands of years of vision and reduces medical expenditures over the lifetime of a cohort of Swedish Type I diabetic patients.

Cohort Studies↗
PubMed1995

Control of limb dynamics in normal subjects and patients without proprioception.

1. We recently showed that patients lacking proprioceptive input from their limbs have particular difficulty performing multijoint movements. In a pantomimed slicing gesture requiring sharp reversals in hand path direction, patients showed large hand path distortions at movement reversals because of failure to coordinate the timing of the separate reversals at the shoulder and elbow joints. We hypothesized that these reversal errors resulted from uncompensated effects of inertial interactions produced by changes in shoulder joint acceleration that were transferred to the elbow. We now test this hypothesis and examine the role of proprioceptive input by comparing the motor performance of five normal subjects with that of two patients with large-fiber sensory neuropathy. 2. Subjects were to trace each of six template lines presented randomly on a computer screen by straight overlapping out-and-back movements of the hand on a digitizing tablet. The lines originated from a common starting position but were in different directions and had different lengths. Directions and lengths were adjusted so that tracing movements would all require the same elbow excursion, whereas shoulder excursion would vary. The effects of varying interaction torques on elbow kinematics were then studied. The subject's dominant arm was supported in the horizontal plane by a low-inertia brace equipped with ball bearing joints and potentiometers under the elbow and shoulder. Hand position was monitored by a magnetic pen attached to the brace 1 cm above a digitizing tablet and could be displayed as a screen cursor. Vision of the subject's arm was blocked and the screen cursor was blanked at movement onset to prevent visual feedback during movement. Elbow joint torques were calculated from joint angle recordings and compared with electromyographic recordings of elbow joint musculature. 3. In control subjects, outward and inward paths were straight and overlapped the template lines regardless of their direction. As prescribed by the task, elbow kinematics remained the same across movement directions, whereas interaction torques varied substantially. The timing of the onsets of biceps activity and the offsets of triceps activity during elbow flexion varied systematically with direction-dependent changes in interaction torques. Controls exploited or dampened these interaction torques as needed to meet the kinematic demands of the task. 4. In contrast, the patients made characteristic errors at movement reversals that increased systematically across movement directions. These reversal errors resulted from improper timing of elbow and shoulder joint reversals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗