Cognitive and structural aspects of addiction: Relation between iris patterns, time perception, eyeblink rate, impulsivity and cigarette addiction

Objectif : Le but de ce travail est d'étudier les corrélations existantes entre les patterns de l'iris, la perception du temps et la fréquence de clignement des paupières (eye blink rate) et ceci en relation avec l'addiction à la cigarette. Méthodologie: Revue de la littérature existante. Expériences sur une cohorte d'au moins trente sujets fumeurs/non-fumeurs. Analyses statistiques. Résultats: Nos résultats confirment qu'il existe des relations entre l'impulsivité, les patterns d'iris, l'eye blink rate spontané et la perception du temps. Nous observons également que l'addiction à la cigarette et son niveau de dépendance ont une influence sur ces différentes mesures. En effet, les sujets fumeurs tendent à avoir une personnalité plus impulsive par rapport aux sujets contrôles. On remarque également une nette diminution de l'eye blink rate dans le groupe des fumeurs et une tendance à la sur-estimation du temps qui passe. Conclusion : Ce travail nous permet de mieux comprendre les différentes corrélations qui existent entre les différentes variables que nous avons mesurées (patterns d'iris, score d'impulsivité et eye blink rate) ainsi que leur relation à l'addiction à la cigarette. Dès lors qu'il est avéré que les fumeurs peuvent avoir une perception du temps altérée par rapport au groupe contrôle, il serait intéressant d'en étudier l'évolution sur le long terme (aggravation avec la durée du tabagisme actif) ainsi que les conséquences qui en découlent écologiquement au moyen d'études longitudinales et de terrain.

Entrance pupil size predicts retinal illumination in darkly pigmented eyes, but not lightly pigmented eyes.

PURPOSE: We determined the effect of entrance pupil size on retinal illumination. The influence of unilateral miosis on the magnitude of the pupil light reflex was studied to ascertain how a clinically significant anisocoria influences the relative afferent pupil defect (RAPD). METHODS: Miosis was induced by topical 1% pilocarpine in the right eye of 14 healthy subjects with normal eyes. The interocular difference in retinal illumination was assessed by computerized pupillometry from the stimulus response curve of the right and left eyes. The main outcome measure was the RAPD, determined by computerized pupillography, at baseline and after pilocarpine-induced anisocoria. RESULTS: Induced anisocoria produced a significant change in RAPD from baseline (mean = 1.60 dB in the miotic eye, P = 0.007). However, anisocoria correlated with RAPD only in subjects with darkly pigmented irides (Pearson correlation coefficient 0.793, P = 0.05). CONCLUSIONS: In darkly pigmented eyes, entrance pupil size significantly influenced the retinal illumination. However, retinal illumination of lightly pigmented eyes is relatively independent of entrance pupil size, presumably due to extrapupillary transmission of light through the iris and sclera. This has important implications in understanding the potential influence of anisocoria on the RAPD and also greater susceptibility of lightly pigmented eyes to light toxicity.

Immune system's role in viral encephalitis.

Viral infections can be a major thread for the central nervous system (CNS), therefore, the immune system must be able to mount a highly proportionate immune response, not too weak, which would allow the virus to proliferate, but not too strong either, to avoid collateral damages. Here, we aim at reviewing the immunological mechanisms involved in the host defense in viral CNS infections. First, we review the specificities of the innate as well as the adaptive immune responses in the CNS, using several examples of various viral encephalitis. Then, we focus on three different modes of interactions between viruses and immune responses, namely human Herpes virus-1 encephalitis with the defect in innate immune response which favors this disease; JC virus-caused progressive multifocal leukoencephalopathy and the crucial role of adaptive immune response in this example; and finally, HIV infection with the accompanying low grade chronic inflammation in the CNS in some patients, which may be an explanation for the presence of cognitive disorders, even in some well-treated HIV-infected patients. We also emphasize that, although the immune response is generally associated with viral replication control and limited cellular death, an exaggerated inflammatory reaction can lead to tissue damage and can be detrimental for the host, a feature of the immune reconstitution inflammatory syndrome (IRIS). We will briefly address the indication of steroids in this situation.

Nocardiose oculaire endogène

IntroductionNous avons diagnostiqué et traité un patient atteint de nocardiose oculaire endogène. Grâce à la chirurgie vitréo-rétinienne, le diagnostique définitif a pu être établi avec un résultat oculaire fonctionnel excellent. La nocardiose oculaire endogène étant une maladie rare, l'image clinique oculaire et la prise en charge n'ont pas encore été décrites systématiquement. Nous avons analysé tous les cas rapportés dans la littérature mondiale (38 cas, publiés jusqu'en 2007) pour trouver des indices sur la physiopathologie, la présentation oculaire, sur la meilleure façon d'établir le diagnostique et sur l'efficacité du traitement antibiotique systémique. Enfin, nous avons établit des directives pour la prise en charge oculaire.La nocardiose (défini comme maladie systémique ou locale) est une maladie touchant surtout des patients immunosupprimés ou immunocompromis comme les patients transplantés, avec maladie auto-immune, atteints du virus HIV sans HAART ou des patients ayant subit un trauma, une opération avec inoculation du germe. Aux Etats-Unis environs 500-1000 nouveaux cas sont diagnostiqués par année avec 20% de dissémination dans des autres organes, le plus fréquemment dans le cerveau. Environs 0.6-1% des patients (3-5 cas/année/US) auront un foyer dans l'oeil, c'est-à-dire la nocardiose oculaire endogène. Nocarida est un Actinomycète, classé comme bactérie, avec une morphologie et un comportement proche aux champignons, avec un cycle de reproduction lente, se trouvant dans la poussière (ubiquitaire) et la matière végétale se décomposant. Elle est sensible aux sulfamides avec émergence de résistances. La mortalité est environs de 25%.RésultatsLa moitié des patients présentait comme premier signe de la maladie systémique des problèmes oculaires, le plus souvent une baisse d'acuité visuelle progressive indolore. Un abcès choroïdien unilatéral unique dans la région maculaire associé ou non à un décollement rétinien séreux et/ou à une vitrite variable était la présentation dans 70% des cas. Nocardia dissémine au niveau des choriocapillaires, rarement, dans l'iris résultant dans un hypopyon isolé. Il y a deux modes de propagation locale: vers l'intérieur, par une nécrose de l'épithélium pigmentaire avec l'envahissement de la rétine et du corps vitré; vers l'extérieure, produisant une sclérite résultant dans une perforation du globe. Avant la séquestration au niveau du corps vitré, la réponse au traitement par antibiose voie générale est favorable: 75% des cas analysés. La rupture de la barrière hémato-oculaire externe (épithélium pigmentaire) peut être mis en évidence par la fluorescence angiographique : les images tardives montrent la diffusion de la fluorescéine dans le corps vitré. Si le corps vitré est atteint, au minimum des injections antibiotiques intravitréen (amikacin), mieux une vitréctomie sont indiqué pour diminuer la charge bactérienne et faciliter la pénétration des antibiotiques donnés par voie systémique. Signes d'une extériorisation d'un abcès choroïdien sont des douleurs intenses, l'exophthalmie et l'hypopyon associé.Soixante-deux pourcents des patients ont souffert d'une dissémination continue par retardement du diagnostique/traitement. La moitié des patients ont eu des abcès cérébraux avant, simultanément ou après présentation. Un quart des patients sont décédés suite de la nocardiose, 32% incluant la maladie de base (tumeur maligne hématologique) ou des autres infections opportunistiques (aspergillose). La morbidité oculaire est importante: un tiers des patients survivants ont retenu une acuité visuelle 0.5 ou mieux, un tiers une acuité visuelle égale ou inférieure à 0.1 et un tiers ont perdu l'oeil par énucléation/éviscération(l). La suspicion clinique et la biopsie de la lésion pour un examen microbiologique direct et des cultures sont cruciales pour la prise en charge. Les risques facteurs sont sexe masculin (4 :1), stéroïdes, immunosuppression pour transplantation ou maladie auto-immune et des tumeurs hématologiques malignes, plus rarement des accidents/ traumas graves. La ponction directe de la lésion assure les meilleures chances pour collectionner un spécimen contenant des bactéries: dans des petits abcès sous-rétiniens maculaires par ponction transvitréenne sous-rétinienne par aiguille fine décrit par le Prof. Augsburger (Référence 7) ou dans des lésions avancées par biopsie sous-rétinienne/rétinienne pendant une vitréctomie selon l'extension et la localisation de l'abcès. Le spécimen doit être préparé pour un examen direct (4 lames) et des cultures utilisant des plaques ordinaires sauf exceptions. La suspicion doit être communiquée au laboratoire et les cultures incubées de façon prolongée (4-6 semaines). Un bilan d'extension avec au minimum un CT scan thoracique et une IRM cérébrale sont indiqués.Le traitement de choix est un antibiotique du groupe des sulfamides à haute dose comme par exemple le co- trimoxazole à double dose. Le choix, le nombre et le dosage du/des médicaments doivent être adapté selon résistance, extension de la maladie, médicaments autres et état de santé général du patient (foie, reins). Les figures 6a et 6b illustrent la prise en charge de patients selon diagnostique établit (Fig. 6b) ou non (Fig 6a).

Down-regulation of NOSII gene expression by iontophoresis of anti-sense oligonucleotide in endotoxin-induced uveitis.

Transcorneoscleral iontophoresis was used to enhance ocular penetration of a 21-bp NH(2) protected anti-NOSII oligonucleotides (ODNs) (fluorescein or infrared-41 labeled) in Lewis rats. Both histochemical localization and acrylamide sequencing gels were used. To evaluate the potential to down-regulate NOSII expression in the rat model of endotoxin-induced uveitis (EIU), anti-sense NOSII ODN, scrambled ODN or saline were iontophorezed into these animals' eyes. Iontophoresis facilitated the penetration of intact ODNs into the intraocular tissues of the rat eye and only the eyes receiving ODNs and electrical current demonstrated intact ODNs within the ocular tissues of both segments of the eye. Iontophoresis of anti-NOSII ODN significantly down-regulated the expression of NOSII expression in iris/ciliary body compared to the saline or scrambled ODN treated eyes. Nitrite production was also significantly reduced in the anti-NOSII applied eyes compared to those treated with saline. Using this system, intraocular delivery of ODNs can be significantly enhanced increasing the potential for successful gene therapy for human eye diseases.

Baerveldt shunts in the treatment of glaucoma secondary to anterior uveal melanoma and proton beam radiotherapy.

INTRODUCTION: Melanoma of the iris and ciliary body may be associated with secondary glaucoma. Treatment with proton beam radiotherapy (PBRT) to the anterior segment can also elevate intraocular pressure (IOP), resulting in uncontrolled glaucoma, often requiring enucleation. This is the first prospective study of Baerveldt aqueous shunts in irradiated eyes with anterior uveal melanoma (AUM; affecting the iris or ciliary body). METHODS: Thirty-one eyes with uncontrolled IOP following anterior segment PBRT treatment for AUM were prospectively recruited to undergo Baerveldt shunt implantation. Postoperative examinations were performed on day 1; weeks 1, 3, 6, 9; months 3, 6, 9, 12 and annually thereafter. Surgical success was defined as IOP 21 mm Hg or less and 20% reduction from baseline. All complications were recorded. RESULTS: Mean follow-up was 15.7 months (SD ±8.3 months). Mean interval from irradiation to shunt implantation was 2.5 years. Mean preoperative IOP was 31.0 (±10.3) mm Hg; mean IOP at last visit was 15.0 (±5.0) mm Hg; mean pre-operative glaucoma medications were 3.3 (±1.3); postoperatively 0.7 (±1.3) glaucoma medications. Surgical success rate was 86% using glaucoma medications. Four eyes had minor postoperative complications, none of which were sight threatening. There were no local tumour recurrences or systemic metastases. There were no enucleations caused by ocular hypertension. CONCLUSIONS: Baerveldt shunts were effective in lowering IOP, with few complications, in eyes treated with total anterior segment irradiation for AUM.

Protease-activated receptor 2 signalling promotes dendritic cell antigen transport and T-cell activation in vivo.

Deficiency of protease-activated receptor-2 (PAR2) modulates inflammation in several models of inflammatory and autoimmune disease, although the underlying mechanism(s) are not understood. PAR2 is expressed on endothelial and immune cells, and is implicated in dendritic cell (DC) differentiation. We investigated in vivo the impact of PAR2 activation on DCs and T cells in PAR2 wild-type (WT) and knockout (KO) mice using a specific PAR2 agonist peptide (AP2). PAR2 activation significantly increased the frequency of mature CD11c(high) DCs in draining lymph nodes 24 hr after AP2 administration. Furthermore, these DCs exhibited increased expression of major histocompatibility complex (MHC) class II and CD86. A significant increase in activated (CD44(+) CD62(-)) CD4(+) and CD8(+) T-cell frequencies was also observed in draining lymph nodes 48 hr after AP2 injection. No detectable change in DC or T-cell activation profiles was observed in the spleen. The influence of PAR2 signalling on antigen transport to draining lymph nodes was assessed in the context of delayed-type hypersensitivity. PAR2 WT mice that were sensitized by skin-painting with fluorescein isothiocyanate (FITC) to induce delayed-type hypersensitivity possessed elevated proportion of FITC(+) DCs in draining lymph nodes 24 hr after FITC painting when compared with PAR2 KO mice (0.95% versus 0.47% of total lymph node cells). Collectively, these results demonstrate that PAR2 signalling promotes DC trafficking to the lymph nodes and subsequent T-cell activation, and thus provides an explanation for the pro-inflammatory effect of PAR2 in animal models of inflammation.

Anterior segment granuloma and optic nerve involvement as the presenting signs of systemic sarcoidosis.

PURPOSE: To report a case with anterior and posterior nodules associated with systemic sarcoidosis. METHODS: A patient with decreased vision underwent complete ophthalmologic examination, ultrasound biomicroscopy, fluorescein and indocyanine green (ICG) angiography. RESULTS: The patient presented a nodule of the iris of the OS and of the optic nerves of both eyes. Chest computed tomography and tissue biopsy established the diagnosis. CONCLUSIONS: Fluorescein and ICG angiography are the only objective exams to demonstrate the extent of ocular involvement in a patient with sarcoidosis.

Disorders of pupillary structure and function.

Neurologists are frequently consulted because of a pupillary abnormality. An unequal size of the pupils, an unusual shape, white colored pupils, or a poorly reactive pupil are common reasons for referral. A directed history and careful observation of the iris and pupil movements can bear out ocular pathology such as congenital or structural anomalies as the cause of abnormal pupils. Thereafter, it is important to evaluate the neurologic causes of anisocoria and poor pupil function. The first part of this article emphasizes pupillary abnormalities frequently encountered in infants and children and discusses some of the more common acquired iris structural defects. The second part focuses on evaluation of lesions in the neural pathways that result in pupillary dysfunction, with particular attention to those conditions having neurologic, systemic, or visual implications.

The prediction of cardiovascular events is improved by combination of Framingham risk score and subclinical atherosclerosis imaging

Purpose: In primary prevention of cardiovascular disease (CVD), it is accepted that the intensity of risk factor treatment should be guided by the magnitude of absolute risk. Risk factors tools like Framingham risk score (FHS) or noninvasive atherosclerosis imaging tests are available to detect high risk subjects. However, these methods are imperfect and may misclassify a large number of individuals. The purpose of this prospective study was to evaluate whether the prediction of future cardiovascular events (CVE) can be improved when subclinical imaging atherosclerosis (SCATS) is combined with the FRS in asymptomatic subjects. Methods: Overall, 1038 asymptomatic subjects (413 women, 625 men, mean age 49.1±12.8 years) were assessed for their cardiovascular risk using the FRS. B-mode ultrasonography on carotid and femoral arteries was performed by two investigators to detect atherosclerotic plaques (focal thickening of intima-media > 1.2 mm) and to measure carotid intima-media thickness (C-IMT). The severity of SCATS was expressed by an ATS-burden Score (ABS) reflecting the number of the arterial sites with >1 plaques (range 0-4). CVE were defined as fatal or non fatal acute coronary syndrome, stroke, or angioplasty for peripheral artery disease. Results: during a mean follow-up of 4.9±3.1 years, 61 CVE were recorded. Event rates the rate of CVE increased significantly from 2.7% to 39.1% according to the ABS (p<0.001) and from 4% to 24.6% according to the quartiles of C-IMT. Similarly, FRS predicted CVE (p<0.001). When computing the angiographic markers of SCATS in addition of FRS, we observed an improvement of net reclassification rate of 16.6% (p< 0.04) for ABS as compared to 5.5% (p = 0.26) for C-IMT. Conclusion: these results indicate that the detection of subjects requiring more attention to prevent CVE can be significantly improved when using both FRS and SCATS imaging.

Efficacy And Safety Of Baerveldt Aqueous Shunts In Glaucoma Secondary To Anterior Segment Irradiation, For Uveal Melanoma

Purpose: Elevated IOP is commonly associated with iris and ciliary body melanoma. Traditional management requires the majority of eyes to undergo enucleation. The authors describe the first series of Baerveldt aqueous shunts in eyes with uveal melanoma, treated by total anterior segment irradiation.Methods: 25 consecutive patients with unilateral iris melanoma were prospectively recruited after obtaining informed consent. All patients underwent anterior segment proton beam irradiation, corneal limbal autografts and Baerveldt tube implantation at Jules Gonin Eye Hospital, Lausanne. Postoperative examinations were performed on day 1, weeks 1,3,6,9 and months 3,6,12 and annually thereafter. Success was defined as: IOP </=18mmHg (definition A); IOP </= 21mmHg and 20% reduction in IOP (definition B). All complications were recorded.Results: Mean age was 53; mean follow up, 10.3 months; mean interval to treatment following irradiation, 2.4 years; mean pre-op IOP was 29.9 mmHg; mean post-op IOP 14.1 mmHg; mean pre-op medications 3.0; post-op medications 1.3. Success rates were, definition A: 95%; definition B: 90%. Only11% had minor complications and there were no sight-threatening complications. Aggressive ocular hypertension was observed in the several eyes prior to shunt implantation. Two eyes were enucleated for non-glaucoma related sequelae.Conclusions: Baerveldt aqueous shunts are safe and efficacious following total anterior segment irradiation for uveal melanoma. The novel interdisciplinary approach improved ocular retention rates, offering a promising alternative to current management algorithms.