Macular sensitivity and fixation patterns in normal eyes and eyes with uveitis with and without macular edema

PURPOSE: This study aims to investigate the relationship between macular sensitivity and thickness in eyes with uveitic macular edema (UME). DESIGN: This study is a prospective observational case series. METHODS: The setting for this study was clinical practice. The study included 59 (28 with UME, 31 without UME) eyes of 26 patients with uveitis and 19 eyes of 10 normal subjects. The procedure followed was fundus-related perimetry and retinal thickness map with an automated fundus perimetry/tomography system. Main outcome measures included quantification of macular sensitivity, fixation pattern, and relationship between macular sensitivity and thickness. RESULTS: Fixation stability revealed that 56 eyes (93.44%) had stable fixation (\u3e75% within the central 2° of point of fixation); three eyes (6.56%) were relatively unstable (75% located within 4°); and no eye had unstable fixation (50% of fixation point within 0.5 mm of foveal center); seven eyes (11.86%) had peri-central fixation location (25% \u3c 50% within 0.5 mm); and seven eyes (11.86%) had eccentric (280 μm. CONCLUSIONS: Perimetry quantification of macular sensitivity and retinal thickness, in association with other factors, may offer novel information regarding the impact of UME on retinal function

Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

<p>Abstract</p> <p>Background</p> <p>In the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events.</p> <p>Methods/Design</p> <p>The Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction (EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years.</p> <p>Discussion</p> <p>The ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome.</p> <p>Trial registration</p> <p>trialregister.nl NTR1108.</p

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Pharmacologic prophylaxis for atrial fibrillation following cardiac surgery: a systematic review

Atrial Fibrillation (AF) is the most common arrhythmia occurring after cardiac surgery. Its incidence varies depending on type of surgery. Postoperative AF may cause hemodynamic deterioration, predispose to stroke and increase mortality. Effective treatment for prophylaxis of postoperative AF is vital as reduces hospitalization and overall morbidity. Beta - blockers, have been proved to prevent effectively atrial fibrillation following cardiac surgery and should be routinely used if there are no contraindications. Sotalol may be more effective than standard b-blockers for the prevention of AF without causing an excess of side effects. Amiodarone is useful when beta-blocker therapy is not possible or as additional prophylaxis in high risk patients. Other agents such as magnesium, calcium channels blocker or non-antiarrhythmic drugs as glycose-insulin - potassium, non-steroidal anti-inflammatory drugs, corticosteroids, N-acetylcysteine and statins have been studied as alternative treatment for postoperative AF prophylaxis

The response of the host microcirculation to bacterial sepsis: Does the pathogen matter?

Sepsis results from the interaction between a host and an invading pathogen. The microcirculatory dysfunction is now considered central in the development of the often deadly multiple organ dysfunction syndrome in septic shock patients. The microcirculatory flow shutdown and flow shunting leading to oxygen demand and supply mismatch at the cellular level and the local activation of inflammatory pathways resulting from the leukocyte-endothelium interactions are both features of the sepsis-induced microcirculatory dysfunction. Although the host response through the inflammatory and immunologic response appears to be critical, there are also evidences that Gram-positive and Gram-negative bacteria can exert different effects at the microcirculatory level. In this review we discuss available data on the potential bacterial-specific microcirculatory alterations observed during sepsis

Much Ado About the TPP’s Effect on Pharmaceuticals

Ocular antigens are sequestered behind the blood-retina barrier and the ocular environment protects ocular tissues from autoimmune attack. The signals required to activate autoreactive T cells and allow them to cause disease in the eye remain in part unclear. In particular, the consequences of peripheral presentation of ocular antigens are not fully understood. We examined peripheral expression and presentation of ocular neo-self-antigen in transgenic mice expressing hen egg lysozyme (HEL) under a retina-specific promoter. High levels of HEL were expressed in the eye compared to low expression throughout the lymphoid system. Adoptively transferred naïve HEL-specific CD4+ T cells proliferated in the eye draining lymph nodes, but did not induce uveitis. By contrast, systemic infection with a murine cytomegalovirus (MCMV) engineered to express HEL induced extensive proliferation of transferred naïve CD4+ T cells, and significant uveoretinitis. In this model, wild-type MCMV, lacking HEL, did not induce overt uveitis, suggesting that disease is mediated by antigen-specific peripherally activated CD4+ T cells that infiltrate the retina. Our results demonstrate that retinal antigen is presented to T cells in the periphery under physiological conditions. However, when the same antigen is presented during viral infection, antigen-specific T cells access the retina and autoimmune uveitis ensues

Programmed Cellular Necrosis Mediated by the Pore-Forming α-Toxin from Clostridium septicum

Programmed necrosis is a mechanism of cell death that has been described for neuronal excitotoxicity and ischemia/reperfusion injury, but has not been extensively studied in the context of exposure to bacterial exotoxins. The α-toxin of Clostridium septicum is a β-barrel pore-forming toxin and a potent cytotoxin; however, the mechanism by which it induces cell death has not been elucidated in detail. We report that α-toxin formed Ca2+-permeable pores in murine myoblast cells, leading to an increase in intracellular Ca2+ levels. This Ca2+ influx did not induce apoptosis, as has been described for other small pore-forming toxins, but a cascade of events consistent with programmed necrosis. Ca2+ influx was associated with calpain activation and release of cathepsins from lysosomes. We also observed deregulation of mitochondrial activity, leading to increased ROS levels, and dramatically reduced levels of ATP. Finally, the immunostimulatory histone binding protein HMGB1 was found to be released from the nuclei of α-toxin-treated cells. Collectively, these data show that α-toxin initiates a multifaceted necrotic cell death response that is consistent with its essential role in C. septicum-mediated myonecrosis and sepsis. We postulate that cellular intoxication with pore-forming toxins may be a major mechanism by which programmed necrosis is induced

THE VALUE OF CLASS-IC ANTIARRHYTHMIC DRUGS FOR ACUTE CONVERSION OF PAROXYSMAL ATRIAL-FIBRILLATION OR FLUTTER TO SINUS RHYTHM

AbstractIn a single-blind randomized study, the efficacy and safety of intravenous propafenone (2 mg/kg body weight per 10 min) versus flecainidc (2 mg/kg per 10 min) were assessed in 50 patients with atrial fibrillation or flutter. Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 (55%) of 20 patients with atrial fibrillation treated with propafenone and in 18 (90%) of 20 with atrial fibrillation treated with flecainide (p < 0.02). If atrial fibrillation was present ⩽24 h, conversion to sinus rhythm was achieved in 8 (57%) of 14 patients in the propafenone group and 13 (93%) of 14 in the flecainide group (p < 0.05). Atrial flutter was converted in two (40%) of five patients treated with propafenone and in one (20%) of five with flecainide (p = NS).Mean time to conversion was 16 ± 10 min in the propafenone group versus 18 ± 13 min in the flecainide group (p = NS). QRS lengthening (83 ± 15 to 99 ± 20 ms) was observed only in the patients treated with flecainide (p < 0.001). Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm. Transient adverse effects were more frequent in the flecainide group (40%) than in the propafenone group (8%) (p < 0.01).In conclusion, at a dose of 2 mg/kg in 10 min, flecainde is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm. However, considering the propafenone plasma levels and very few adverse effects, the dose or infusion rate, or both, used in the propafenone group may not have been sufficient to achieve an optimal effect. Neither drug seems very effective in patients with atrial flutter