A presentation of aids-related ophthalmic disease in a severely immunocompromised patient

Background: Human immunodeficiency virus (HIV) retinopathy is the most common ocular manifestation of the acquired immunodeficiency syndrome (AIDS), serving as an important marker for patients with significantly compromised immune status who are at risk for developing severe and visionthreatening ocular opportunistic infections. This case report describes a presentation of HIV retinopathy and cytomegalovirus (CMV) retinitis, and reviews the current management options. Case Report: A 40-year-old black male presented for a comprehensive eye exam to rule out HIV-related ophthalmic disease. At his initial visit, a dilated fundus examination revealed HIV retinopathy of the left eye. Upon subsequent examinations and as his immune status diminished, the patient developed CMV retinitis of the right eye. The patient was treated successfully with a course of highly active antiretroviral therapy (HAART) and oral valgancyclovir.  Conclusion: CMV retinitis is the most common ocular opportunistic infection associated with AIDS. Treatment with systemic HAART and concomitant anti-CMV therapy leads to reconstitution of the immune system and regression of the retinitis. &nbsp

Présentation d'une maladie ophthalmique liée au SIDA chez un patient sévèrement immunodéprimé

Contexte : La rétinopathie liée au virus de l’immunodéficience humaine (VIH) est la manifestation oculaire la plus courante du syndrome d’immunodéficience acquise (SIDA), servant de marqueur important chez les patients présentant un état immunitaire fortement déprimé qui sont à risque de contracter des infections oculaires opportunistes sévères qui menacent la vision. Le présent rapport de cas décrit une présentation d’une rétinopathie à VIH et d’une rétinite à cytomégalovirus (CMV) et examine les options de prise en charge actuellement utilisées. Rapport de cas : Un homme de race noire de 40 ans se présente pour un examen complet de la vue afin d’exclure la possibilité d’une maladie ophtalmique liée au VIH. À ses premières visites, un examen du fond de l’œil à pupilles dilatées révèle une rétinopathie au VIH à l’œil gauche. Après d’autres examens et du fait que sa capacité immunitaire diminuait, le patient contracte une rétinite à CMV dans l’œil droit. On administre avec succès au patient un traitement antirétroviral hautement actif (HAART) et du valgancyclovir par voie orale. Conclusion : La rétinite à CMV est l’infection oculaire opportuniste la plus courante associée au SIDA. Un traitement systémique HAART et une thérapie concomitante contre le CMV permettent de reconstituer le système immunitaire et de faire régresser la rétinite

A comparative study of the efficiency of chart versus computer-generated contrast sensitivity testing in glaucoma patients and controls

Purpose. The goal of this study was to assess the efficiency of chart vs. computergenerated contrast sensitivity tests in glaucoma patients and controls. Methods. A total of 64 individuals (30 young controls, 18 older controls, 16 glaucoma patients) were tested for contrast sensitivity using 4 different tests. Two tests determined contrast sensitivity (CS) for detecting large targets with sharp borders. One of these was the MARS printed chart, and the other a computerized number search test by Bailey. The second assessment determined spatial contrast sensitivity (SCS) for sinusoidal grating targets at several spatial frequencies. One of these was the printed Vistech chart, the other a computerized test by Faubert. Results. Both CS tests showed a decrease in the glaucoma group versus both the control groups (p < 0.001). The tests for SCS demonstrated a decrease in sensitivity both with age (p < 0.001) and in the presence of glaucoma (p < 0.001) across all spatial frequencies. Conclusion. The data indicated that SCS was superior in separating the three study groups. Neither of the computer-generated tests was more sensitive than its printed counterpart

TRIM68 negatively regulates IFN-β production by degrading TRK fused gene, a novel driver of IFN-β downstream of anti-viral detection systems.

In recent years members of the tripartite motif-containing (TRIM) family of E3 ubiquitin ligases have been shown to both positively and negatively regulate viral defence and as such are emerging as compelling targets for modulating the anti-viral immune response. In this study we identify TRIM68, a close homologue of TRIM21, as a novel regulator of Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I IFN production. Proteomic analysis of TRIM68-containing complexes identified TRK-fused gene (TFG) as a potential TRIM68 target. Overexpression of TRIM68 and TFG confirmed their ability to associate, with TLR3 stimulation appearing to enhance the interaction. TFG is a known activator of NF-κB via its ability to interact with inhibitor of NF-κB kinase subunit gamma (IKK-γ) and TRAF family member-associated NF-κB activator (TANK). Our data identifies a novel role for TFG as a positive regulator of type I IFN production and suggests that TRIM68 targets TFG for lysosomal degradation, thus turning off TFG-mediated IFN-β production. Knockdown of TRIM68 in primary human monocytes resulted in enhanced levels of type I IFN and TFG following poly(I:C) treatment. Thus TRIM68 targets TFG, a novel regulator of IFN production, and in doing so turns off and limits type I IFN production in response to anti-viral detection systems

Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

<p><b>Background</b> <br>Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality.</br></p> <p><b>Methods</b> <br>We assessed the −1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20 842 patients with coronary heart disease, 35 206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12 785 incident cases of coronary heart disease during 2·79 million person-years at risk). We analysed −1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy.</br></p> <p><b>Findings</b> <br>The minor allele frequency of −1131T>C was 8% (95% CI 7—9). −1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3·5% [95% CI 2·6—4·6]; 0·053 mmol/L [0·039—0·068]), lower apolipoprotein AI (1·3% [0·3—2·3]; 0·023 g/L [0·005—0·041]), and higher apolipoprotein B (3·2% [1·3—5·1]; 0·027 g/L [0·011—0·043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16·0% (95% CI 12·9—18·7), or 0·25 mmol/L (0·20—0·29), higher (p=4·4×10−24). The odds ratio for coronary heart disease was 1·18 (95% CI 1·11—1·26; p=2·6×10−7) per C allele, which was concordant with the hazard ratio of 1·10 (95% CI 1·08—1·12) per 16% higher triglyceride concentration recorded in prospective studies. −1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12·2 nmol/L [95% CI 7·7—16·7]; p=9·3×10−8) and smaller HDL particle size (0·14 nm [0·08—0·20]; p=7·0×10−5), factors that could mediate the effects of triglyceride.</br></p> <p><b>Interpretation</b> <br>These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease.</br></p> <p><b>Funding</b> <br>British Heart Foundation, UK Medical Research Council, Novartis.</br></p&gt