A sore red eye with systemic involvement

The study of happiness has long been a playground for philosophical speculation. By lack of empirical measures of happiness, it was not possible to check propositions about the matter. In the late 20th century, survey-research methods introduced by the social sciences have brought a break-through. Dependable measures of happiness have developed, by means of which a significant body of knowledge has evolved

Predictors of Long-Term Visual Outcome in Intermediate Uveitis

PURPOSE: To describe factors that predict visual loss and complications in intermediate uveitis. DESIGN: Cross-sectional study. PARTICIPANTS: Subjects with intermediate uveitis were identified from a database of 1254 uveitis patients seen in the clinic of a single consultant (S.L.L.) between 2011 and 2013. S METHODS: Information was gathered from the clinical notes of all subjects examined in clinic. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), moderate visual loss (MVL; ≤20/50), severe visual loss (SVL; ≤20/200). RESULTS: Three hundred and five subjects (550 eyes) were included in the study, comprising 24.3% of subjects seen in clinic. Mean (± standard deviation) age at diagnosis was 40.9±16.9 years, and 64.6% of subjects were female. Median follow-up was 8.2 years (mean, 9.7 years, 5452 eye-years). Systemic diagnosis was made in 36.1% of patients, with sarcoidosis (22.6%) and multiple sclerosis (4.6%) the most frequent systemic associations. Median BCVA was 20/30 (mean logarithm of the minimum angle of resolution [logMAR] 0.26±0.38, n = 550 eyes) at presentation, 20/30 (mean logMAR 0.22±0.42, n = 430) at 5 years, and 20/30 (mean logMAR 0.23±0.46, n = 260) at 10 years. Macular edema was observed in 224 eyes (40.7%) and was associated with idiopathic disease (P = 0.001) and diabetes (P = 0.001). Topical therapy was used in 82.7%, and 34.2% received local injections of corticosteroids. A total of 50.5% required oral steroids and 13.8% required second-line immunosuppression. Subjects with a diagnosis of sarcoidosis were less likely to require a second-line agent (4.3% vs. 16.2%, P = 0.011). On multivariate analysis, visual acuity at referral, retinal pigment epithelial atrophy, and macular scarring were associated with increased risk of MVL; and visual acuity at referral, local therapy, macular scarring, retinal detachment, and hypotony and phthisis were associated with increased risk of SVL. CONCLUSIONS: Intermediate uveitis has a long disease course with frequent complications and often requires systemic treatment. Despite this, most subjects are still able to achieve good long-term visual outcomes

Eye care in the intensive care unit

Ocular surface disease is common in the intensive care population with 20–42% of patients developing corneal epithelial defects. The ocular surface is normally protected by the ability to produce tears, to blink and to close the eyes with rest or sleep. All of these mechanisms can be disrupted in the intensive care population, increasing the risk of developing ocular surface disease. Despite the scale of the problem, eye-care protocols are commonly not instigated and documentation of eye care is often poor. This review details the risk factors for developing ocular surface disease. It also provides evidence-based guidance on protecting the eyes in vulnerable patients, identifying diseases affecting the eye in intensive care patients and delivering the best treatment to the eye. There is growing evidence that adherence to a correctly performed eye-care guideline prevents the majority of corneal problems encountered in the intensive care unit

Mathematical Modelling of Endocrine Systems

This is the final (in press) version. Available from Elsevier via the DOI in this recordHormone rhythms are ubiquitous and essential to sustain normal physiological functions. Combined mathematical modelling and experimental approaches have shown that these rhythms result from regulatory processes occurring at multiple levels of organisation and require continuous dynamic equilibration, particularly in response to stimuli. We review how such an interdisciplinary approach has been successfully applied to unravel complex regulatory mechanisms in the metabolic, stress, and reproductive axes. We discuss how this strategy is likely to be instrumental for making progress in emerging areas such as chronobiology and network physiology. Ultimately, we envisage that the insight provided by mathematical models could lead to novel experimental tools able to continuously adapt parameters to gradual physiological changes and the design of clinical interventions to restore normal endocrine function.Medical Research Council (MRC)Engineering and Physical Sciences Research Council (EPSRC)Wellcome Trus

Foundations of Black Hole Accretion Disk Theory

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at http://www.livingreviews.org/lrr-2013-

Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome

Somatostatin (SS) and dopamine (DA) receptors are widely expressed in neuroendocrine tumours that cause Cushing's Syndrome (CS). Increasing knowledge of specific subtype expression within these tumours and the ability to target these receptor subtypes with high-affinity compounds, has driven the search for new SS- or DA-based medical therapies for the various forms of CS. In Cushing's disease, corticotroph adenomas mainly express dopamine receptor subtype 2 (D2) and somatostatin receptor subtype 5 (sst5), whereas sst2is expressed at lower levels. Activation of these receptors can inhibit ACTH-release in primary cultured corticotroph adenomas and compounds that target either sst5(pasireotide, or SOM230) or D2(cabergoline) have shown significant efficacy in subsets of patients in recent clinical studies. Combination therapy, either by administration of both types of compounds separately or by treatment with novel somatostatin-dopamine chimeric molecules (e.g. BIM-23A760), appears to be a promising approach in this respect. In selected cases of Ectopic ACTH-producing Syndrome (EAS), the sst2-preferring compound octreotide is able to reduce cortisol levels effectively. A recent study showed that D2receptors are also significantly expressed in the majority of EAS and that cabergoline may decrease cortisol levels in subsets of these patients. In both normal adrenal tissue as well as in adrenal adenomas and carcinomas that cause CS, sst and DA receptor expression has been demonstrated. Although selected cases of adrenal CS may benefit from sst or DA-targeted treatment, its total contribution to the treatment of these patients is likely to be low as surgery is effective in most cases

Reply

Refers to: Koushik Tripathy, Re: Niederer et al.: Predictors of long-term visual outcome, in: intermediate uveitis (Ophthalmology. 2017;124:393-398) Ophthalmology, Volume 124, Issue 7, July 2017, Pages e59. https://doi.org/10.1016/j.ophtha.2017.02.01

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man

Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy

Continuous Free Cortisol Profiles in Healthy Men - Validation of Microdialysis Method

Abstract Context In humans, approximately 95% of circulating cortisol is bound to corticosteroid-binding globulin and albumin. It is only the free fraction that is biologically active and can activate signalling pathways via glucocorticoid hormone receptors in cells. Microdialysis is a well-established technique that enables the sampling of molecules in different compartments of the body, including extracellular fluid. This is the first study validating a rapid sampling microdialysis method measuring free cortisol in the subcutaneous and blood compartments of healthy volunteers. Methods Healthy non-smoking volunteers (42 men; age 18-24 years; BMI 18-25 kg/m2) received placebo (saline), 250 µg Synacthen or 1 mg dexamethasone with ten minutely sampling to measure total and free cortisol (subcutaneous, intravenous and saliva) for an hour before and 4 hours after administration. Results Following stimulation by Synacthen, total serum cortisol and free cortisol in both compartments rose significantly, achieving and maintaining maximum levels between 2 and 3 hours following the stimulus. A decline in cortisol levels was evident after the administration of dexamethasone or placebo, but there was a clear pulsatile activity around lunchtime in the latter group which was prominent in the blood compartment (total and free cortisol). There was good correlation between serum total and free cortisol (SC and intravenous) in the Synacthen and dexamethasone groups with no significant delay (less than 5 minutes) between total and free cortisol. Conclusions This seminal study demonstrated the dynamic responses of total blood cortisol and microdialysis derived free cortisol in blood, subcutaneous tissue and saliva in man. </jats:sec