The characterization of retinal phenotype in a family with C1QTNF5-related late-onset retinal degeneration.

PURPOSE: To describe the clinical, spectral-domain optical coherence tomography and electrophysiological features of C1QTNF5-associated late-onset retinal degeneration in a molecularly confirmed pedigree. METHODS: Five members of a family participated, and affected individuals (n = 4) underwent detailed ophthalmologic evaluation including fundus autofluorescence and spectral-domain optical coherence tomography imaging and electroretinography. Electrooculography was performed in three individuals. RESULTS: The visual acuity was initially normal and worsened with time. Anterior segment abnormalities included peripupillary iris atrophy and long anterior insertion of zonules. Peripapillary atrophy, drusenoid deposition, and scalloped sectorial chorioretinal atrophy were observed in all older individuals (n = 3). Fundus autofluorescence demonstrated hypofluorescent areas corresponding to regions of chorioretinal atrophy. The spectral-domain optical coherence tomography demonstrated multiple areas of retinal pigment epithelium-Bruch membrane separation with intervening homogeneous deposition that corresponded to the drusenoid lesions and areas of chorioretinal atrophy. Electrooculography was normal in one individual and showed abnormally low dark trough measures in older individuals (n = 2). Electroretinography was normal in early stages (n = 1), but showed marked abnormalities in the rod system (n = 3), which was predominantly inner retinal (n = 2) in late stages. CONCLUSION: Late-onset retinal degeneration is a progressive degeneration, and anterior segment abnormalities present early. The widespread sub-retinal pigment epithelium deposition seen on spectral-domain optical coherence tomography in older individuals appears to be a characteristic in late stages. Electrooculography demonstrates abnormalities only in late stages of the disease.

Overexpression of a mutant form of TGFBI/BIGH3 induces retinal degeneration in transgenic mice.

PURPOSE: Despite ubiquitous expression of the keratoepithelin (KE) protein encoded by the transforming growth factor beta induced/beta induced gene human clone 3 (TGFBI/BIGH3) gene, corneal dystrophies are restricted to the cornea, and no other tissues are affected. We investigated the role of TGFBI/BIGH3 in Groenouw corneal dystrophies by generating transgenic mice overexpressing TGFBI/BIGH3 containing the R555W mutation. METHODS: Transgenic animals expressing the Groenouw mutation of human TGFBI/BIGH3 were generated using lentiviral vectors. The line expressed TGFBI/BIGH3 containing the R555W mutation under the control of the phosphoglycerate kinase (PGK) promoter. Expression of the transgene was monitored by Southern and western blotting and by RT-PCR. Electroretinogram analysis was performed and four mice were subjected to complete necroscopy. RESULTS: Transgene expression was observed in different organs although without specific expression in the cornea. The overall morphology of the transgenic animals was not severely affected by KE overexpression. However, we observed an age-dependent retinal degeneration both functionally and histologically. Female-specific follicular hyperplasia in the spleen and increased levels of lipofuscin in the adrenal gland were also seen in transgenic animals. CONCLUSIONS: Cellular degeneration in the retina of transgenic animals suggest that perturbation of the transforming growth factor beta (TGFbeta) family regulation may affect photoreceptor survival and may induce possible accelerated aging in several tissues. No corneal phenotype could be observed, probably due to the lack of transgene expression in this tissue.

Morgagnian cataract simulating iris neoplasia : case report

Purpose: to describe a case in which the diagnosis of Morganian cataract required clinical and instrumental differentiation from iris pathologies, including iris melanoma. Methods: a 60-years-old Caucasian man referred to our institute for worsening of vision in last few months. Clinical evaluation consisted in complete ophthalmological assessment, ultrasound examination (biomicroscopy and 20MHz), and Magnetic Resonance Imaging (MRI) completed with Susceptibility Weighted Imaging (SWI). Results: traumatic corneal wound of the left eye (LE) had occurred 5 years before, and was treated with medical therapy alone. Best-corrected visual acuity (BCVA) was 3/10 in the right eye (RE) and finger count in the LE, with intraocular pressure at 13 and 20mmHg, respectively. Chronic central serous chorioretinopathy, accounted for the low visual acuity of the RE. Slit-lamp biomicroscopy of the LE was as in Figure 1; LE fundus was not clinically observable. Despite MRI was compatible with an iris solid formation, characterized by contrast enhancement and hyperintense signal in SWI, ultrasound indicated rather a mixed solid and liquid content (moderately echogenic external layer, hyporeflective internal content). Iris root and ciliary body were not significantly altered; the lens showed inhomogeneous content. We considered Morgagnian cataract the most probable diagnosis. Surgery confirmed the presence of a hypermature cataract with prior anterior capsule fissuring; the liquefied cortex infiltrated the iris without anterior chamber seeping. Post-operative BCVA was 3/10 and fundus examination disclosed an advanced macular chronic central serous chorioretinopathy. Conclusions: In the reported case a previous perforating trauma have probably damaged the lens capsule and started cataract progression. Curiously cataract developed percolating into the iris stroma, thus simulating an iris mass. At our knowledge, Morgagnian cataract has never been included in the differential diagnosis of iris mass.

Deep sclerectomy combined with trabeculectomy in pediatric glaucoma.

PURPOSE: To evaluate the outcomes of combined deep sclerectomy and trabeculectomy (penetrating deep sclerectomy) in pediatric glaucoma. DESIGN: Retrospective, nonconsecutive, noncomparative, interventional case series. PARTICIPANTS: Children suffering from pediatric glaucoma who underwent surgery between March 1997 and October 2006 were included in this study. METHODS: A primary combined deep sclerectomy and trabeculectomy was performed in 35 eyes of 28 patients. Complete examinations were performed before surgery, postoperatively at 1 and 7 days, at 1, 2, 3, 4, 6, 9, and 12 months, and then every 6 months after surgery. MAIN OUTCOME MEASURES: Surgical outcome was assessed in terms of intraocular pressure (IOP) change, additional glaucoma medication, complication rate, need for surgical revision, as well as refractive errors, best-corrected visual acuity (BCVA), and corneal clarity and diameters. RESULTS: The mean age before surgery was 3.6+/-4.5 years, and the mean follow-up was 3.5+/-2.9 years. The mean preoperative IOP was 31.9+/-11.5 mmHg. At the end of follow-up, the mean IOP decreased by 58.3% (P<0.005), and from 14 patients with available BCVA 8 patients (57.1%) achieved 0.5 (20/40) or better, 3 (21.4%) 0.2 (20/100), and 2 (14.3%) 0.1 (20/200) in their better eye. The mean refractive error (spherical equivalent [SE]) at final follow-up visits was +0.83+/-5.4. Six patients (43%) were affected by myopia. The complete and qualified success rates, based on a cumulative survival curve, after 9 years were 52.3% and 70.6%, respectively (P<0.05). Sight-threatening complications were more common (8.6%) in refractory glaucomas. CONCLUSIONS: Combined deep sclerectomy and trabeculectomy is an operative technique developed to control IOP in congenital, secondary, and juvenile glaucomas. The intermediate results are satisfactory and promising. Previous classic glaucoma surgeries performed before this new technique had less favorable results. The number of sight-threatening complications is related to the severity of glaucoma and number of previous surgeries. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus.

Keratoconus, a common inherited ocular disorder resulting in progressive corneal thinning, is the leading indication for corneal transplantation in the developed world. Genome-wide association studies have identified common SNPs 100 kb upstream of ZNF469 strongly associated with corneal thickness. Homozygous mutations in ZNF469 and PR domain-containing protein 5 (PRDM5) genes result in brittle cornea syndrome (BCS) Types 1 and 2, respectively. BCS is an autosomal recessive generalized connective tissue disorder associated with extreme corneal thinning and a high risk of corneal rupture. Some individuals with heterozygous PRDM5 mutations demonstrate a carrier ocular phenotype, which includes a mildly reduced corneal thickness, keratoconus and blue sclera. We hypothesized that heterozygous variants in PRDM5 and ZNF469 predispose to the development of isolated keratoconus. We found a significant enrichment of potentially pathologic heterozygous alleles in ZNF469 associated with the development of keratoconus (P = 0.00102) resulting in a relative risk of 12.0. This enrichment of rare potentially pathogenic alleles in ZNF469 in 12.5% of keratoconus patients represents a significant mutational load and highlights ZNF469 as the most significant genetic factor responsible for keratoconus identified to date.

Role of Notch signaling in epidermis and appendages

Résumé Dans la peau, il a été montré que Notch1 induit l'arrêt de la prolifération et la différentiation des keratinocytes. L'inactivation de Notch1 cause une hyperplasie de l'épiderme et la formation de carcinomes basaux cellulaires. Notre groupe a principalement identifié deux voies de signalisations, la voie Shh et la voie Wnt, qui sont dérégulées en conséquence de l'inactivation de Notch1 dans la peau. Nous avons démontré l'habilité de Notch1 à réprimer la voie Wnt induite par ß-catenin dans les keratinocytes primaires ainsi que dans d'autres types de cellules épithéliales humaines. De plus, nous avons pu déterminer que Notch1 régule cette voie, probablement en favorisant la phosphorylation de ß-catenin par le complexe axin/APC/GSK-3ß. La protéine faisant partie de la voie Wnt, ou la protéine affectant la voie Wnt, qui est régulée par Notch1 est sujette à de plus amples investigations. Un autre but de cette étude a été l'identification de potentiels gènes cibles de Notch1 autres que ceux faisant partie des voies de signalisation Shh et Wnt précédemment évoquées. Ce projet fut abordé par l'analyse de puces à ADN (ISREC et Affymetrix) qui ont été utilisées pour des expériences de gain et de perte de fonction de Notch1 dans des keratinocytes prúmaires. En plus de l'hyperplasie épidermale, les souris Notch1 déficiente ont une perte importante de poils. Nous avons montré que Notch1 est nécessaire pour le développement et l'homéostasie des follicules pileux. En effet, l'inactivation du gène Notch1 mediée par l'activation des kératines 5 ou 14 dans l'épiderme, cause des défauts du cycle ainsi que de la structure des poils. De plus, d'autres appendices de la peau, comme les glandes sudoripares et de Meibomius, ont une structure anormale et sont non fonctionnelles dans les souris Notch1 déficiente. Finalement, nous avons observé que la déficience de Notch1 dans l'épithélium cornéen mène à la formation d'une plaque épidermale opaque sur la cornée. Basé sur l'hypothèse que le défaut des glandes de Meibomius des souris Notch1 déficientes cause des lésions de la surface oculaire, nous avons montré que Notch1 est essentiel pour la cicatrisation de la cornée. Lorsque Notch1 est absent, les cellules souches de l'épithélium cornéen ne sont plus capables de se différentier en cellules cornéennes, mais réparent la blessure en se différentiant en épiderme. Ce résultat indique que Notch1 est essentiel pour la différentiation de cellules souches de la cornée qui sont spécifiquement impliquées dans la réparation de la cornée. De plus, nous avons montré que l'expression de CRBP1 dans l'épithélium cornéen est diminuée en l'absence de Notch1, ceci étant possiblement à l'origine de la formation de la plaque épidermale. Abstract: In the skin, Notch1 has been shown to trigger cell growth arrest and differentiation of keratinocytes. Notch1 inactivation results in epidermal hyperplasia and subsequent formation of basal cell carcinoma-like (BCC-like) tumors. So far our group has identified two main pathways, the Shh and the Wnt pathway, that are deregulated as a consequence of Notch1 inactivation in the skin. We showed the ability of Notch1 to represses ß-catenin-mediated Wnt signaling in primary keratinocytes as well as in other types of human epithelial cells. In addition we were able to determine that Notch1 regulates this pathway possibly by enhancing ß-catenin phosphorylation by the axin/APC/GSK-3ß complex. The exact target protein of the Wnt pathway or target protein that affects the Wnt pathway, and that is regulated by Notch1, is subject of current investigation. Another aim of this study was the identification of possible Notch1 target genes in addition to those of the Shh and Wnt signaling pathways. This was addressed by gene chip analysis using ISREC as well as Affymetrix microarrays for gain and loss of function of Notch1 in mouse primary keratinocytes. In addition to epidermal hyperplasia, Notch1 deficient mice show an important hair loss. We showed that Notch1 is required for postnatal development and homeostasis of hair follicles. Indeed, keratin5 or keratinl4-driven Cre recombinase-mediated inactivation of the Notch1 gene in the epidermis causes perturbations of the hair cycle and structural defects of the hair follicle. Moreover, other skin appendages, like the sweat and Meibomian glands show abnormal morphology and are not functional in the Notch 1 deficient mice. Finally, we observed that Notch1 deficiency in the corneal epithelium leads to the formation of an epidermal corneal plaque. Based on the hypothesis that the Meiboinian gland defect in the Notch1 deficient mice results in lesions of the eye surface, we showed that Notch1 is essential for wound-healing of the cornea. In absence of Notch1 the stem cells of the corneal epithelium are no longer able to differentiate in the corneal fate but instead repair the wound by differentiating into skin-like epidermis. This result indicated that Notch1 is essential for the differentiation of corneal stem cells specifically implicated in corneal wound-healing. Moreover, we showed that CRBP1 expression in the corneal epithelium was lost in the absence of Notch1, possibly being at the origin of plaque formation.

Prognostication in comatose survivors of cardiac arrest: An advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine.

OBJECTIVES: To review and update the evidence on predictors of poor outcome (death, persistent vegetative state or severe neurological disability) in adult comatose survivors of cardiac arrest, either treated or not treated with controlled temperature, to identify knowledge gaps and to suggest a reliable prognostication strategy. METHODS: GRADE-based systematic review followed by expert consensus achieved using Web-based Delphi methodology, conference calls and face-to-face meetings. Predictors based on clinical examination, electrophysiology, biomarkers and imaging were included. RESULTS AND CONCLUSIONS: Evidence from a total of 73 studies was reviewed. The quality of evidence was low or very low for almost all studies. In patients who are comatose with absent or extensor motor response at ≥72 h from arrest, either treated or not treated with controlled temperature, bilateral absence of either pupillary and corneal reflexes or N20 wave of short-latency somatosensory evoked potentials were identified as the most robust predictors. Early status myoclonus, elevated values of neuron-specific enolase at 48-72 h from arrest, unreactive malignant EEG patterns after rewarming, and presence of diffuse signs of postanoxic injury on either computed tomography or magnetic resonance imaging were identified as useful but less robust predictors. Prolonged observation and repeated assessments should be considered when results of initial assessment are inconclusive. Although no specific combination of predictors is sufficiently supported by available evidence, a multimodal prognostication approach is recommended in all patients.

Cornea graft endothelial cells undergo apoptosis by way of an alternate (caspase-independent) pathway.

PURPOSE: To look for apoptosis pathways involved in corneal endothelial cell death during acute graft rejection and to evaluate the potential role of nitric oxide in this process. MATERIALS AND METHODS: Corneal buttons from Brown-Norway rats were transplanted into Lewis rat corneas. At different time intervals after transplantation, apoptosis was assessed by diamino-2-phenylindol staining and annexin-V binding on flat-mount corneas, and by terminal transferase dUTP nick end labeling (TUNEL), caspase-3 dependent and leukocyte elastase inhibitor (LEI)/LDNase II caspase-independent pathways on sections. Inducible nitric oxide synthase (NOS-II) expression and the presence of nitrotyrosine were assayed by immunohistochemistry. RESULTS: Graft endothelial cells demonstrated nuclear fragmentation and LEI nuclear translocation, annexin-V binding, and membranes bleb formation. Apoptosis associated with caspase-3 activity or TUNEL-positive reaction was not observed at any time either in the graft or in the recipient corneal endothelial cells. During 14 days posttransplantation, the recipient corneal endothelial cells remained unaltered and their number unchanged in all studied corneas. NOS-II was expressed in infiltrating cells present within the graft. This expression was closely associated with the presence of nitrotyrosine in endothelial and infiltrating cells. CONCLUSION: During the time course of corneal graft rejection, graft endothelial cells undergo apoptosis. Apoptosis is caspase 3 independent and TUNEL negative and is, probably, carried out by an alternative pathway driven by an LEI/L-Dnase II. Peroxynitrite formation may be an additional mechanism for cell toxicity and programmed cell death of the graft endothelial cells during the rejection process in this model.

Physical activity and pregnancy: cardiovascular adaptations, recommendations and pregnancy outcomes.

Regular physical activity is associated with improved physiological, metabolic and psychological parameters, and with reduced risk of morbidity and mortality. Current recommendations aimed at improving the health and well-being of nonpregnant subjects advise that an accumulation of > or =30 minutes of moderate physical activity should occur on most, if not all, days of the week. Regardless of the specific physiological changes induced by pregnancy, which are primarily developed to meet the increased metabolic demands of mother and fetus, pregnant women benefit from regular physical activity the same way as nonpregnant subjects. Changes in submaximal oxygen uptake (VO(2)) during pregnancy depend on the type of exercise performed. During maternal rest or submaximal weight-bearing exercise (e.g. walking, stepping, treadmill exercise), absolute maternal VO(2) is significantly increased compared with the nonpregnant state. The magnitude of change is approximately proportional to maternal weight gain. When pregnant women perform submaximal weight-supported exercise on land (e.g. level cycling), the findings are contradictory. Some studies reported significantly increased absolute VO(2), while many others reported unchanged or only slightly increased absolute VO(2) compared with the nonpregnant state. The latter findings may be explained by the fact that the metabolic demand of cycle exercise is largely independent of the maternal body mass, resulting in no absolute VO(2) alteration. Few studies that directly measured changes in maternal maximal VO(2) (VO(2max)) showed no difference in the absolute VO(2max) between pregnant and nonpregnant subjects in cycling, swimming or weight-bearing exercise. Efficiency of work during exercise appears to be unchanged during pregnancy in non-weight-bearing exercise. During weight-bearing exercise, the work efficiency was shown to be improved in athletic women who continue exercising and those who stop exercising during pregnancy. When adjusted for weight gain, the increased efficiency is maintained throughout the pregnancy, with the improvement being greater in exercising women. Regular physical activity has been proven to result in marked benefits for mother and fetus. Maternal benefits include improved cardiovascular function, limited pregnancy weight gain, decreased musculoskeletal discomfort, reduced incidence of muscle cramps and lower limb oedema, mood stability, attenuation of gestational diabetes mellitus and gestational hypertension. Fetal benefits include decreased fat mass, improved stress tolerance, and advanced neurobehavioural maturation. In addition, few studies that have directly examined the effects of physical activity on labour and delivery indicate that, for women with normal pregnancies, physical activity is accompanied with shorter labour and decreased incidence of operative delivery. However, a substantial proportion of women stop exercising after they discover they are pregnant, and only few begin participating in exercise activities during pregnancy. The adoption or continuation of a sedentary lifestyle during pregnancy may contribute to the development of certain disorders such as hypertension, maternal and childhood obesity, gestational diabetes, dyspnoea, and pre-eclampsia. In view of the global epidemic of sedentary behaviour and obesity-related pathology, prenatal physical activity was shown to be useful for the prevention and treatment of these conditions. Further studies with larger sample sizes are required to confirm the association between physical activity and outcomes of labour and delivery.

PAX6 mutations in Egyptian families with aniridia

Methods Ten patients with aniridia from 3 families of Egyptian origin underwent full ophthalmologic, general and neurological examination, and blood drawing. Cerebral MRI was performed in the index case of each family. Genomic DNA was prepared from venous leukocytes and direct sequencing of all the exons and intron-exon junctions of the PAX6 gene was performed after PCR amplification. Results Common features observed in the three families included absence of iris tissue, corneal pannus with different degrees of severity and foveal hypoplasia with severely reduced visual acuity. In families 2 and 3, additional findings such as lens dislocation, lens opacities or polar cataract and glaucoma were observed. We identified two novel (c.170-174delTGGGC [p.L57fs17] and c.475delC [p.R159fs47]) and one known (c.718C>T) PAX6 mutations in the affected members of the 3 families. Systemic and neurological examination was normal in all ten affected patients. Cerebral MRI showed absence of the pineal gland in all three index patients. Severe hypoplasia of the brain anterior commissure was associated to the p.L57fs17mutation, absence of the posterior commissure to both p.R159fs47 and p.R240X, and optic chiasma atrophy and almost complete agenesis of the corpus callosum to p.R240X. Conclusions We identified two novel PAX6 mutations in families with severe aniridia from Northern Egypt, an ethnic group which is not well studied. In addition to common phenotype of aniridia and despite normal neurological examination, absence of the pineal gland was observed in all 3 index patients. The heterogeneity of brain anomalies related to PAX6 mutations is underexplored and is highlighted in this study.

Kératocône bilatéral évolué [Bilateral keratoconus: a case report].

Among corneal dystrophies, the keratoconus is one of the most frequently observed among young adults. A clinico pathological case is reported in a 13-year-old-girl of African origin. The diagnosis of bilateral keratoconus was established based on the obvious changes of the corneal curvature and thickness. After an unsuccessful attempt to improve vision with contact lenses, a keratoplasty was finally performed on one side to remove the pathological cornea. Its histopathological study found the characteristic changes of keratoconus: breaks of Bowman's layer and corneal thinning.

Ocular antisense oligonucleotide delivery by cationic nanoemulsion for improved treatment of ocular neovascularization: an in-vivo study in rats and mice.

The efficacy of an antisense oligonucleotide (ODN17) cationic nanoemulsion directed at VEGF-R2 to reduce neovascularization was evaluated using rat corneal neovascularization and retinopathy of prematurity (ROP) mouse models. Application of saline solution or scrambled ODN17 solution on eyes of rats led to the highest extent of corneal neovascularization. The groups treated with blank nanoemulsion or scrambled ODN17 nanoemulsion showed moderate inhibition in corneal neovascularization with no significant difference with the saline and scrambled ODN17 control solution groups, while the groups treated with ODN17 solution or Avastin® (positive ODN17 control) clearly elicited marked significant inhibition in corneal neovascularization confirming the results reported in the literature. The highest significant corneal neovascularization inhibition efficiency was noted in the groups treated with ODN17 nanoemulsion (topical and subconjunctivally). However, in the ROP mouse model, the ODN17 in PBS induced a 34% inhibition of retinal neovascularization when compared to the aqueous-vehicle-injected eyes. A significantly higher inhibition of vitreal neovascularization (64%) was observed in the group of eyes treated with ODN17 nanoemulsion. No difference in extent of neovascularization was observed between blank nanoemulsion, scrambled ODN17 nanoemulsion, vehicle or non-treated eyes. The overall results indicate that cationic nanoemulsion can be considered a promising potential ocular delivery system and an effective therapeutic tool of high clinical significance in the prevention and forthcoming treatment of ocular neovascular diseases.

Prise en charge du traumatisme cranio-cérébral sévère [Update on the management of severe traumatic brain injury]

Prognosis after severe traumatic brain injury (TBI) is determined by the severity of initial injury and secondary cerebral damage. The main determinants of secondary cerebral damage are brain ischemia and oedema. Traumatic brain injury is a heterogeneous disease. Head CT-scan is essential in evaluating initial type of injury and severity of brain oedema. A standardised approach based on prevention and treatment of secondary cerebral damage is the only effective therapeutic strategy of severe TBI. We review the classification, pathophysiology and treatment of secondary cerebral damage after severe TBI and discuss the management of intracranial hypertension, cerebral perfusion pressure and brain ischemia.

Ocular biocompatibility of novel Cyclosporin A formulations based on methoxy poly(ethylene glycol)-hexylsubstituted poly(lactide) micelle carriers.

Topical ocular drug delivery has always been a challenge for pharmaceutical technology scientists. In the last two decades, many nano-systems have been studied to find ways to overcome the typical problems of topical ocular therapy, such as difficult corneal penetration and poor drug availability. In this study, methoxy poly(ethylene glycol)-hexylsubstituted poly(lactides) (MPEG-hexPLA) micelle formulations, which are promising nanocarriers for poorly water soluble drugs, were investigated for the delivery of Cyclosporin A (CsA) to the eye. As a new possible pharmaceutical excipient, the ocular compatibility of MPEG-hexPLA micelle formulations was evaluated. An in vitro biocompatibility assessment on human corneal epithelial cells was carried out using different tests. Cytotoxicity was studied by using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT), and clonogenic tests and revealed that the CsA formulations and copolymer solutions were not toxic. After incubation with MPEG-hexPLA micelle formulations, the activation of caspase-dependent and -independent apoptosis as well as autophagy was evaluated using immunohistochemistry by analyzing the localization of four antibodies: (1) anti-caspase 3; (2) anti-apoptotic inducing factor (AIF); (3) anti-IL-Dnase II and (4) anti-microtubule-associated protein 1 light chain 3 (LC3). No apoptosis was induced when the cells were treated with the micelle solutions that were either unloaded or loaded with CsA. The ocular tolerance was assessed in vivo on rabbit eyes by Confocal Laser Scanning Ophthalmoscopy (CLSO), and very good tolerability was seen. The observed corneal surface was comparable to a control surface that was treated with a 0.9% NaCl solution. In conclusion, these results demonstrate that MPEG-hexPLA micelles are promising drug carriers for ocular diseases involving the activation of cytokines, such as dry eye syndrome and autoimmune uveitis, or for the prevention of corneal graft rejection.

Le point sur l'ergométrie en 2012 dans le diagnostic de la maladie coronarienne.

Background In patients presenting with acute cardiac symptoms, abnormal ECG and raised troponin, myocarditis may be suspected after normal angiography. Aims To analyse cardiac magnetic resonance (CMR) findings in patients with a provisional diagnosis of acute coronary syndrome (ACS) in whom acute myocarditis was subsequently considered more likely. Methods and results 79 patients referred for CMR following an admission with presumed ACS and raised serum troponin in whom no culprit lesion was detected were studied. 13% had unrecognised myocardial infarction and 6% takotsubo cardiomyopathy. The remainder (81%) were diagnosed with myocarditis. Mean age was 45615 years and 70% were male. Left ventricular ejection fraction (EF) was 58610%; myocardial oedema was detected in 58%. A myocarditic pattern of late gadolinium enhancement (LGE) was detected in 92%. Abnormalities were detected more frequently in scans performed within 2 weeks of symptom onset: oedema in 81% vs 11% (p<0.0005), and LGE in 100% vs 76% (p<0.005). In 20 patients with both an acute (<2 weeks) and convalescent scan (>3 weeks), oedema decreased from 84% to 39% (p<0.01) and LGE from 5.6 to 3.0 segments (p¼0.005). Three patients presented with sustained ventricular tachycardia, another died suddenly 4 days after admission and one resuscitated 7 weeks following presentation. All 5 patients had preserved EF. Conclusions Our study emphasises the importance of access to CMR for heart attack centres. If myocarditis is suspected, CMR scanning should be performed within 14 days. Myocarditis should not be regarded as benign, even when EF is preserved.