The multifocal pattern electroretinogram in chloroquine retinopathy

Purpose: Optimal screening for ocular toxicity caused by chloroquine and hydroxychloroquine is still controversial. With the multifocal pattern electroretinogram (mfPERG), a new electrophysiological technique has recently become available to detect early changes of ganglion cells. In this study this new technique is applied to a series of 10 patients seen consecutively receiving long-term chloroquine medication. Methods: In 10 patients receiving chloroquine medication, clinical examination, Amsler visual field testing and computerized color vision testing were performed. If toxicity was suspected, automated perimetry was carried out. In addition, in all patients conventional pattern electroretinogram (PERG) and mfPERG testing were performed. Results: On clinical examination 8 patients showed no chloroquine-associated maculopathy, while 2 patients did. Of these 2, only 1 reported abnormalities when viewing the Amsler chart, while automated perimetry showed typical, ring-like paracentral scotomas in both affected patients and color vision was significantly abnormal. In the normal patients, 4 of 8 had a mild color vision disturbance, which correlated to age-related macular changes. The amplitudes of the PERG and the central (approximately 10degrees) responses of the mfPERG were markedly reduced in chloroquine maculopathy, while the latencies were unchanged. The peripheral rings of mfPERG (ranging to 48degrees) were not affected by chloroquine toxicity. Both PERG and mfPERG were less affected by age-related macular changes. Conclusions: The reduction of PERG and central mfPERG responses in chloroquine maculopathy may help with the early detection of toxicity. Copyright (C) 2004 S. Karger AG, Basel

The Retention of Fallout Particles on Roofs Having Different Slopes

Since World War II the continual buildup and spread of nuclear arms has produced a pressure situation between nations. As more and more nations become nuclear powers and continue to expand their arsenals, the chance of a nuclear attack, either by accident or by specific intent, increases. If a full-scale nuclear attack should develop, the only chance of survival would rest -with a fully prepared population. Even with a fully prepared population many would not survive. The National Fallout Shelter Program is helpful in preventing casualties in the event of a nuclear attack. Studies show, however, that such casualties would be very high. The reason for this conclusion is that it is economically unfeasible to protect all of the people from the immediate effects of a nuclear explosion consisting of initial radiation, thermal radiation, and blast. A significant number of people could survive if they were provided protection from radioactive fallout. A complete fallout shelter program would accomplish this

JRIF: Reactive Information Flow Control for Java

A reactive information flow (RIF) automaton for a value v specifies (i) allowed uses for v and (ii) the RIF automaton for any value that might be directly or indirectly derived from v. RIF automata thus specify how transforming a value alters how the result might be used. Such labels are more expressive than existing approaches for controlling downgrading. We devised a type system around RIF automata and incorporated it into Jif, a dialect of Java that supports a classic form of labels for information flow. By implementing a compiler for the resulting JRIF language, we demonstrate how easy it is to replace a classic information-flow type system by a more expressive RIF-based type system. We programmed two example applications in JRIF, and we discuss insights they provide into the benefits of RIF-based security labels.Supported in part by AFOSR grants F9550-06-0019 and FA9550-11-1-0137, National Science Foundation grants 0430161, 0964409, and CCF-0424422 (TRUST), ONR grants N00014-01- 1-0968 and N00014-09-1-0652, and grants from Microsoft

Usefulness of Published PCR Primers in Detecting Human Rhinovirus Infection

We conducted a preliminary comparison of the relative sensitivity of a cross-section of published human rhinovirus (HRV)–specific PCR primer pairs, varying the oligonucleotides and annealing temperature. None of the pairs could detect all HRVs in 2 panels of genotyped clinical specimens; >1 PCR is required for accurate description of HRV epidemiology

The multifocal pattern electroretinogram in glaucoma

AbstractBackground: The pattern ERG can be used to detect early glaucomatous change, because the response of cells in the inner retina from (typically) 20°–40° of area is reduced before perimetric abnormality is certain. The multifocal pattern electroretinogram (mfPERG) allows analysis of many local regions within this area. The aim of this study was to investigate whether in patients with presumed glaucoma the mfPERG permits diagnosis and discrimination from normals.Methods: Measurements on 25 age-related normal eyes were compared to those on 23 eyes with different stages of glaucoma. A RETIScan system was used to generate a stimulus pattern of 19 hexagons, each consisting of six triangles. The triangles pattern-reversed black to white at 75 Hz. Those 19 hexagons were grouped into three stimulus regions: a central field, a middle, and a peripheral ring. The complete array subtended 48° at the eye. The hexagons alternated between black and white, in a temporal pattern that followed a corrected binary m-sequence (length 512, 10 cycles with 39 s each). The amplitudes and latencies of positive responses at approximately 50 ms (P-50) and negative responses at approximately 95 ms (N-95) were analyzed.Results: In patients with glaucoma the P-50 and N-95 components of the mfPERG were significantly reduced for the central area and both outer rings compared to normal volunteers (p<0.001, Mann–Whitney-U). The most distinct reduction was observed for N-95 and the central ring. Changes in latencies were not conclusive. The reduction of the components increased with the stage of glaucoma. A predictive model for detecting early glaucomatous changes was designed based on P-50–N-95 with 88% sensitivity and 76% specificity.Conclusion: In glaucoma a marked reduction of components, especially centrally is observed in the mfPERG. This hints to an early involvement of central ganglion cells and may be useful for future functional tests

The Electro-oculographic Responses to Alcohol and Light in a Series of Patients with Retinitis Pigmentosa

PURPOSE. Alcohol produces changes in the electro-oculogram (EOG) similar to those caused by light, but indirect evidence indicates that alcohol directly affects the retinal pigment epithelium (RPE). An investigation of the alcohol-induced increase (termed the alcohol rise in this study) in patients with disease of the photoreceptors was therefore of interest. METHODS. Standard EOGs were recorded after oral administration of alcohol in a group of patients with retinitis pigmentosa (RP). RESULTS. The average response of 17 patients to alcohol was a slow decrease of potential, which contrasts with the normal alcohol rise. In patients with considerable residual peripheral field, alcohol produced a small increase of voltage, followed by a prolonged decrease. The slower decrease in the EOG voltage was evident in patients with small fields and could be seen even in those who had lost all visual function. Light caused small increments of EOG voltage (termed light rises), again related to the field size. CONCLUSIONS. It is probable that the intracellular signaling system that causes the alcohol and light rises is lost in RP. (Invest Ophthalmol Vis Sci. 2000;41:2730 -2734 T he light-induced increase (termed light rise in this study) of the EOG is produced by the liberation of an unknown substance from the retina, which has been shown to affect second-messenger systems in the apical membrane of the RPE. 1,2 Results in a companion study 3 demonstrated that small oral doses of alcohol produce an effect on the EOG that is indistinguishable from that evoked by light, except for a delay due to the time required to absorb alcohol from the gut. The interactions between alcohol and light were investigated, and the inference from the results was that alcohol (similar to other agents) is able to alter the basolateral conductance of the RPE by a pathway that probably involves second messengers, but not the retina. 5 Because many of the photoreceptors in such retinas are nonfunctional, the failure to release a light rise substance is not surprising, and the EOG light rise is known to be greatly reduced. METHODS Seventeen patients were recruited by contacting the British Retinitis Pigmentosa Society, by letter and on its Web sites, and asking for volunteers, who were then given a written explanation of the proposed test, so they could provide informed consent. All the patients were under the care of specialist eye departments. One patient was excluded because he had bilateral cataract extraction with ocular implants. We did not accept patients under 18 years of age or those with other systemic conditions. The age range was between 22 and 74 years. The work was performed in accordance with the Declaration of Helsinki. Standard EOG recordings of 30°horizontal eye movements were made as described in a previous article, 3 except in the case of patients with very reduced vision, when the patients made extreme eye movements that were measured as 90°. The (ethyl) alcohol was administered after subjects fasted for more than 12 hours (0.3 g/kg, 20% wt/vol in water, drunk in 15 seconds). Other clinical tests (fields, electroretinograms [ERGs]) were performed in a standard fashion in patients with the best preserved vision to confirm clinical diagnoses. ERGs were elicited by equipment (a LED-powered miniganzfeld stimulus) similar to that already described

The Human Electro-oculogram: Interaction of Light and Alcohol

PURPOSE. To investigate the production of the voltage changes evoked in the retinal pigment epithelium (RPE) by light and alcohol and the interaction of these agents. METHODS. The eye movement potential in humans was intermittently recorded to standard horizontal excursions for long periods during which either retinal illumination was altered or ethyl alcohol was administered by the oral, intragastric, or intravenous route. In other experiments, both light and alcohol were administered. RESULTS. Alcohol and light produced near identical corneofundal voltage changes (positive and then negative) over more than 40 minutes. Differences in timing between alcohol and light increases are explicable by the delays in alcohol absorption. Weak background light suppressed the effect of light steps, and low levels of background alcohol suppressed the response to subsequent doses. Backgrounds of one agent did not affect the voltage changes caused by the other. Minimal alcohol effects were seen after administration of 1 g orally or 270 mg intravenously-that is, doses that produced undetectable changes in breath alcohol. The semisaturating oral dose was approximately 20 mg/kg. CONCLUSIONS. Alcohol and light act through separate pathways to form a final common pathway inside the RPE cell that is responsible for triggering the timing of the slow oscillatory changes of EOG voltage. The sensitivity and duration with which alcohol affects the RPE are comparable with the effect of melatonin or dopamine, although only the former interacts with light similarly to alcohol. Transient modulation of the acetylcholine (Ach) neuronal receptor occurs at similar sensitivity, but all other known actions of alcohol require higher concentrations than this RPE action. (Invest Ophthalmol Vis Sci. 2000;41:2722-2729 S ince the original descriptions of the electro-oculogram (EOG) in humans, 1-4 intraretinal microelectrode recordings 5-10 have elucidated the underlying mechanisms. Light adaptation of the retina changes the quantity of an unknown substance or substances, probably produced by photoreceptors, that diffuses to the apical processes of the retinal pigment epithelium (RPE) where it binds to membrane-bound chemical receptors. These then liberate an intracellular second messenger that ultimately depolarizes the basolateral surface of the RPE cells, causing a light-induced increase in the corneofundal potential (hereafter termed light rise), by increasing the chloride conductance. 11 The external and internal transmitters are unknown, as is the relationship between the transmitter concentration and the stereotyped voltage changes. Thus, the time course of the concentration changes of the external or the internal transmitter may determine the timing of the light rise and the subsequent oscillations. The EOG remains a useful clinical test, 12-18 because it offers an overview of the functioning of photoreceptors, subretinal space, and RPE, but because light is used to provoke the voltage changes, retinal and RPE dysfunction cannot be separated. Therefore, other agents, such as bicarbonate ions, acetazolamide, and hyperosmotic solutions, which act directly on the RPE, have been investigated. 18 -22 All have been found to cause a slow decrease in corneofundal potential. Previous experiments METHODS Subjects Three students aged 20 to 25 years and the authors (seventh decade) gave informed consent, and the experimental protocols complied with the Helsinki declaration. Recording Techniques Five-millimeter chloride-coated silver disc electrodes were placed on each temple, near the lateral canthi, and a similar earth electrode was placed on the forehead. The recording was bitemporal (i.e., the voltages were generated by both eyes). Standard 30°horizontal eye movements were made at two per From the Applie