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

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

Continuous Free Cortisol Profiles – Circadian Rhythms in Healthy Men

The pituitary-adrenal axis had historically been considered a representative model for circadian rhythms. A recently developed portable collection device provided the opportunity to evaluate free cortisol profiles using the microdialysis approach in individuals free to conduct their day-to-day activities in their own surroundings. Methods Two separate experiments were conducted in healthy male volunteers – ten-minutely total and subcutaneous free cortisol were measured for 24-hour period in one and twenty-minutely subcutaneous free cortisol for 72 consecutive hours in free-living individuals in the other experiment. Results The characteristic circadian rhythm was evident in both serum total and subcutaneous free cortisol with the lowest levels being achieved and maintained in the hours surrounding sleep onset with peak levels occurring in every individual around waking. In all free-living individuals, the circadian rhythm was consistent across 72-hours despite a wide range of activities. All participants also showed increased cortisol following the consumption of lunch. The lowest levels during all 24 hour periods were observed during the hours following lights switch-off, at the onset of sleep Conclusions This is the first study to show up to three consecutive 24-hour measurements of subcutaneous free cortisol in healthy individuals. This, we believe is a landmark study that paves the way for ambulatory monitoring of free cortisol profiles continuously up to a period of 72 hours in a free-living individual going about their day to day activities whether in health or in diseases involving the HPA axis

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

Ultradian Cortisol Pulsatility Encodes a Distinct, Biologically Important Signal

Cortisol is released in ultradian pulses. The biological relevance of the resulting fluctuating cortisol concentration has not been explored.Determination of the biological consequences of ultradian cortisol pulsatility.A novel flow through cell culture system was developed to deliver ultradian pulsed or continuous cortisol to cells. The effects of cortisol dynamics on cell proliferation and survival, and on gene expression were determined. In addition, effects on glucocorticoid receptor (GR) expression levels and phosphorylation, as a potential mediator, were measured.Pulsatile cortisol caused a significant reduction in cell survival compared to continuous exposure of the same cumulative dose, due to increased apoptosis. Comprehensive analysis of the transcriptome response by microarray identified genes with a differential response to pulsatile versus continuous glucocorticoid delivery. These were confirmed with qRT-PCR. Several transcription factor binding sites were enriched in these differentially regulated target genes, including CCAAT-displacement protein (CDP). A CDP regulated reporter gene (MMTV-luc) was, as predicted, also differentially regulated by pulsatile compared to continuous cortisol delivery. Importantly there was no effect of cortisol delivery kinetics on either GR expression, or activation (GR phosphoSer(211)).Cortisol oscillations exert important effects on target cell gene expression, and phenotype. This is not due to differences in cumulative cortisol exposure, or either expression, or activation of the GR. This suggests a novel means to regulate GR function