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David Robert Grimes - One of the best experts on this subject based on the ideXlab platform.
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Simulation of parabolic reflectors for Ultraviolet Phototherapy.
Physics in medicine and biology, 2016Co-Authors: David Robert GrimesAbstract:Ultraviolet (UVR) Phototherapy is widely used to treat an array of skin conditions, including psoriasis, eczema and vitiligo. For such interventions, a quantified dose is vital if the treatment is to be both biologically effective and to avoid the detrimental effects of over-dosing. As dose is absorbed at surface level, the orientation of patient site with respect to the UVR lamps modulates effective dose. Previous investigations have modelled this behaviour, and examined the impact of shaped anodized aluminium reflectors typically placed around lamps in Phototherapy cabins. These mirrors are effective but tend to yield complex patterns of reflection around the cabin which can result in substantial dose inhomogeneity. There has been some speculation over whether using the reflective property of parabolic mirrors might improve dose delivery or homogeneity through the treatment cabin. In this work, the effects of parabolic mirrors are simulated and compared with standard shaped mirrors. Simulation results strongly suggest that parabolic reflectors reduce total irradiance relative to standard shaped reflectors, and have a negligible impact on dose homogeneity.
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Ultraviolet radiation therapy and UVR dose models.
Medical physics, 2014Co-Authors: David Robert GrimesAbstract:Ultraviolet radiation (UVR) has been an effective treatment for a number of chronic skin disorders, and its ability to alleviate these conditions has been well documented. Although nonionizing, exposure to Ultraviolet (UV) radiation is still damaging to deoxyribonucleic acid integrity, and has a number of unpleasant side effects ranging from erythema (sunburn) to carcinogenesis. As the conditions treated with this therapy tend to be chronic, exposures are repeated and can be high, increasing the lifetime probability of an adverse event or mutagenic effect. Despite the potential detrimental effects, quantitative Ultraviolet dosimetry for Phototherapy is an underdeveloped area and better dosimetry would allow clinicians to maximize biological effect whilst minimizing the repercussions of overexposure. This review gives a history and insight into the current state of UVR Phototherapy, including an overview of biological effects of UVR, a discussion of UVR production, illness treated by this modality, cabin design and the clinical implementation of Phototherapy, as well as clinical dose estimation techniques. Several dose models for Ultraviolet Phototherapy are also examined, and the need for an accurate computational dose estimation method in Ultraviolet Phototherapy is discussed.
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A computational simulation of reflector and tube effects in Ultraviolet Phototherapy
Physics in medicine and biology, 2012Co-Authors: David Robert GrimesAbstract:While Ultraviolet Phototherapy is effective at treating a wide range of skin conditions, over exposure to Ultraviolet radiation has a number of detrimental effects including but not limited to erythema, ocular damage and even oncogenesis. It is therefore important to quantify and control the dose received in order to maximize the effectiveness of treatment while minimizing the potentially damaging side effects. Recent dose models have been developed for this purpose, incorporating both the irradiance from the Phototherapy lamps and the contributions from metallic reflectors. These models have good predictive power, but the situation is complicated by the huge variety of cabin and mirror geometries available. This work simulates a variety of possible treatment configurations to examine the implications these factors have on dose homogeneity and global irradiance, and shows that the relationship between global irradiance and number of tubes is complex and nonlinear. This has implications for both cabin design and treatment planning.
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Development of a radiation computation dose model for use in Ultraviolet Phototherapy
2011Co-Authors: David Robert GrimesAbstract:The ultimate motivation for this research is to investigate and quantify the nature of Ultraviolet radiation for medical application over a variety of skin diseases. While application of both narrow-band and broad-band Ultraviolet light have demonstrated great success in the treatment of a multitude of dermatological conditions, over-exposure to this section of the electromagnetic spectrum can be detrimental to human health, and the crux of the issue is striking a balance between maintaining a biologically effective dose while minimizing the impact on the overall health of the patient. Treatment cabins typically consist of a series of Ultraviolet emitting lamps surrounded by an array of anodized aluminium reflectors positioned around the lamp to increase the incident dose on the patient in the treatment cabin. Many different factors are important in estimating the patient dose, including the nature of lamp emission, the properties and placement of the reflectors and the position and self-shielding from the patient as well as cabin geometry. Lamp failure can also occur, complicating matters. A dose model that estimates all these factors and quantifies them could be of use in a variety of clinical applications. This research focuses on methods of quantifying these various elements contributing to patient dose, and the creation of a dose model for patients undergoing Ultraviolet Phototherapy.
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Reflection modeling in Ultraviolet Phototherapy.
Medical physics, 2011Co-Authors: David Robert Grimes, Chris Robbins, C J Martin, Graeme Phanco, Neil O'hareAbstract:Purpose: Ultraviolet Phototherapy is a widely used treatment which has exceptional success with a variety of skin conditions. Over-exposure to Ultraviolet radiation (UVR) can however be detrimental and cause side effects such as erythema, photokeratisis, and even skin cancer. Quantifying patient dose is therefore imperative to ensure biologically effective treatment while minimizing negative repercussions. A dosemodel for treatment would be valuable in achieving these ends. Methods: Prior work by the authors concentrated on modeling the output of the lamps used in treatment and it was found a line source model described the output from the sources to a high degree. In practice, these lamps are surrounded by reflective anodized aluminum in patient treatment cabins and this work extends the model to quantify specular reflections from these planes on patient dose. Results: The extension of the model to allow for reflected images in addition to tube output shows a remarkably good fit to the actual data measured. Conclusions: The reflection model yields impressive accuracy and is a good basis for full UVR cabin modeling.
Colin J Martin - One of the best experts on this subject based on the ideXlab platform.
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Instrument for scanning the angular variation of irradiance in Ultraviolet Phototherapy cabinets.
Journal of medical engineering & technology, 2002Co-Authors: A. L. Evans, Colin J Martin, G D Currie, D. Smith, S. Mccalman, D. Bilsland, S. DunnAbstract:An instrument is described that measures irradiance and the angular distribution of the intensity of Ultraviolet radiation sources inside Phototherapy cabinets. Failed lamps and lamps with higher or lower outputs are readily identified. The measurements are controlled from outside the cabinet, thus reducing the risk to staff from exposure to Ultraviolet radiation.
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An automated dosimetry system for testing whole-body Ultraviolet Phototherapy cabinets
Physics in medicine and biology, 2000Co-Authors: G D Currie, Colin J Martin, A. L. Evans, D. Smith, S. Mccalman, D. BilslandAbstract:A new technique is described for automated Ultraviolet dosimetry within whole-body Phototherapy cabinets. A dual-head detector system has been designed, permitting simultaneous assessment of irradiance levels and radiant intensities from individual lamps. One detector is used in combination with a diffuser/filter system for the measurement of irradiance and the other is mounted at the end of a slit collimator to provide a measurement which can be related to the radiant intensities of the individual lamps. These quantities are derived from 800 separate measurements made during rotation of the detector head around a 360 degrees circle at a fixed height and position within the cabinet under remote computer software control. The device has advantages compared with standard techniques, enabling measurements to be made without the need for a person to be present in the cabinet. A full set of measurements is made with minimal switching of the power supply to the lamps. This simplifies the assessment and reduces the uncertainty from variation in output after the lamps are switched on. Variations in irradiance with orientation for the smaller Phototherapy cabinets are clearly demonstrated. Plots of data from the collimated detector show peaks corresponding to the lamps and the surrounding reflectors. The plots enable failed lamps to be detected and peak values can be related to radiant intensities of individual lamps.
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A study of the directional response of Ultraviolet radiometers: II. Implications for Ultraviolet Phototherapy derived from computer simulations
Physics in medicine and biology, 2000Co-Authors: Colin J Martin, Stephen D. PyeAbstract:A theoretical model has been used to simulate irradiances for Ultraviolet (UV) Phototherapy cabinets and other sources. The accuracy of the simulation results has been checked by comparison with experimental measurements. The simulations have been used to study the influence of different factors on UV Phototherapy exposure and to develop recommendations for the operation and calibration of Phototherapy cabinets. Many radiometers used in the evaluation of skin doses have input optics with directional responses that are not proportional to the cosine of the angle of incidence for the UV radiation. Data on radiometer directional responses have been incorporated into the simulations, which show that the poor directional responses for some radiometers currently in use will give errors of 20-50% in the assessment of irradiance. The influence of lamp source geometries employed for radiometer calibration has been investigated. UV Phototherapy dosimetry commonly uses a spectroradiometer and a radiometer in the transfer of irradiance calibrations from a small standard UV lamp to a large-area source with a different UV spectrum. Recommendations are given on the range of acceptability for radiometer directional responses and a method is described for determining whether these are fulfilled. Recommendations are made on the techniques that should be used for calibration.
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The importance of radiometer angular response for Ultraviolet Phototherapy dosimetry.
Physics in medicine and biology, 1999Co-Authors: Colin J Martin, G D Currie, Stephen D. PyeAbstract:The influence of the angular response of radiometer probes on measurements of irradiance in Ultraviolet Phototherapy has been studied. Irradiance measurements were made using nine Ultraviolet (UV) radiometers employed by Phototherapy centres in Scotland and Northern Ireland, and compared with measurements made using two spectroradiometers. The light sources used were UVB TL01 fluorescent lamps, arranged in different geometries. Irradiances within TL01 whole body treatment cabinets were assessed based on a comparison with one of the spectroradiometers. The results show variations of 50% in cabinet irradiance measurements made by different radiometers, even when they were calibrated using the same source geometry and spectroradiometer. Differences in radiometer probe design and construction lead to an under- or over-response at angles of incidence greater than zero. Angular responses of different probes were assessed using banks of fluorescent lamps. The differences found are large enough to account for the variations in measurements of cabinet irradiance. The variations in irradiance measurements are significant in terms of planning and monitoring patient exposure during TL01 Phototherapy. Accurate dosimetry can only be achieved if radiometer probes have a good cosine response and recommendations are made for better calibration techniques.
Stephen D. Pye - One of the best experts on this subject based on the ideXlab platform.
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A study of the directional response of Ultraviolet radiometers: II. Implications for Ultraviolet Phototherapy derived from computer simulations
Physics in medicine and biology, 2000Co-Authors: Colin J Martin, Stephen D. PyeAbstract:A theoretical model has been used to simulate irradiances for Ultraviolet (UV) Phototherapy cabinets and other sources. The accuracy of the simulation results has been checked by comparison with experimental measurements. The simulations have been used to study the influence of different factors on UV Phototherapy exposure and to develop recommendations for the operation and calibration of Phototherapy cabinets. Many radiometers used in the evaluation of skin doses have input optics with directional responses that are not proportional to the cosine of the angle of incidence for the UV radiation. Data on radiometer directional responses have been incorporated into the simulations, which show that the poor directional responses for some radiometers currently in use will give errors of 20-50% in the assessment of irradiance. The influence of lamp source geometries employed for radiometer calibration has been investigated. UV Phototherapy dosimetry commonly uses a spectroradiometer and a radiometer in the transfer of irradiance calibrations from a small standard UV lamp to a large-area source with a different UV spectrum. Recommendations are given on the range of acceptability for radiometer directional responses and a method is described for determining whether these are fulfilled. Recommendations are made on the techniques that should be used for calibration.
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The importance of radiometer angular response for Ultraviolet Phototherapy dosimetry.
Physics in medicine and biology, 1999Co-Authors: Colin J Martin, G D Currie, Stephen D. PyeAbstract:The influence of the angular response of radiometer probes on measurements of irradiance in Ultraviolet Phototherapy has been studied. Irradiance measurements were made using nine Ultraviolet (UV) radiometers employed by Phototherapy centres in Scotland and Northern Ireland, and compared with measurements made using two spectroradiometers. The light sources used were UVB TL01 fluorescent lamps, arranged in different geometries. Irradiances within TL01 whole body treatment cabinets were assessed based on a comparison with one of the spectroradiometers. The results show variations of 50% in cabinet irradiance measurements made by different radiometers, even when they were calibrated using the same source geometry and spectroradiometer. Differences in radiometer probe design and construction lead to an under- or over-response at angles of incidence greater than zero. Angular responses of different probes were assessed using banks of fluorescent lamps. The differences found are large enough to account for the variations in measurements of cabinet irradiance. The variations in irradiance measurements are significant in terms of planning and monitoring patient exposure during TL01 Phototherapy. Accurate dosimetry can only be achieved if radiometer probes have a good cosine response and recommendations are made for better calibration techniques.
Jared Jagdeo - One of the best experts on this subject based on the ideXlab platform.
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MicroRNA expression analysis of human skin fibroblasts treated with high-fluence light-emitting diode-red light.
Journal of biophotonics, 2019Co-Authors: Andrew Mamalis, Eugene Koo, Clifford G. Tepper, Jared JagdeoAbstract:Skin fibrosis is a chronic debilitating feature of several skin diseases that lead to characteristic increases in dermal fibroblast proliferation and collagen deposition through upregulation in components of the transforming growth factor beta (TGF-B)/SMAD pathway. In contrast to Ultraviolet Phototherapy, high-fluence light-emitting diode-generated red light (HF-LED-RL, 633 ± 15 nm) is a safe, economic and non-invasive therapy with in vitro evidence that supports modulation of the key cellular characteristics involved in the pathogenesis of skin fibrosis. Limited data exists pertaining to the effects of HF-LED-RL on human skin fibroblast microRNA (miRNA). Herein, we explored the effects of HF-LED-RL on fibroblast miRNA levels using RNA-seq and miRNA expression analysis. Using RNA-seq analysis we found that HF-LED-RL at 320 and 640 J/cm2 increased transcription of key miRNA that are involved in skin fibrosis including miRNA-29, miRNA-196a and Let-7a, and decreased transcription of miRNA-21, miRNA-23b and miRNA-31. These microRNA findings provide insight into the molecular underpinnings of HF-LED-RL and highlight potential therapeutic targets of interest for the treatment of skin fibrosis. Additional research on the specific molecular mechanisms underlying HF-LED-RL effects on fibroblasts may provide further mechanistic insight into this therapy and may reveal additional future therapeutic targets for skin fibrosis.
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The Combination of Resveratrol and High-Fluence Light Emitting Diode-Red Light Produces Synergistic Photobotanical Inhibition of Fibroblast Proliferation and Collagen Synthesis: A Novel Treatment for Skin Fibrosis.
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.], 2017Co-Authors: Andrew Mamalis, Jared JagdeoAbstract:BACKGROUND Skin fibrosis is a debilitating condition that significantly impacts patient quality of life. Ultraviolet Phototherapy is currently used to treat several diseases featuring skin fibrosis. High-fluence light-emitting diode-generated red light (HF-LED-RL) does not cause DNA damage associated with skin cancer, and it is generally regarded as safe, portable, and cost-effective. Early clinical observations suggest that LED-generated light may possess antifibrotic effects, although these findings are largely unexplored. Previously published research demonstrated that HF-LED-RL decreases fibroblast proliferation and collagen in vitro. OBJECTIVE The goal of this study was to compare the combination effects of HF-LED-RL alone with HF-LED-RL in combination with resveratrol. MATERIALS AND METHODS It is hypothesized that resveratrol, an active ingredient in red wine, a potent antioxidant scavenger of reactive oxygen species, and an inhibitor of collagen production, may synergistically decrease fibroblast proliferation and collagen production when combined with HF-LED-RL. RESULTS In this study, evidence is provided that resveratrol combined with HF-LED-RL acts synergistically to decrease fibroblast proliferation and procollagen 1A1 production, and this represents a new potential therapeutic modality that is termed the "photobotanical" effect due to the combined light and botanical properties observed. CONCLUSION The study, discovery, and use of photobotanical combinations may usher in new therapeutics or Phototherapy adjuvants for the treatment of dermatologic diseases.
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Resveratrol Prevents Reactive Oxygen Species-Induced Effects of Light-Emitting Diode-Generated Blue Light in Human Skin Fibroblasts.
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.], 2016Co-Authors: Andrew Mamalis, Eugene Koo, Jared JagdeoAbstract:Light-emitting diode-generated blue light (LED-BL) is part of the visible light spectrum that does not cause DNA damage and may represent a safer alternative to Ultraviolet Phototherapy. Previous research demonstrated that LED-BL can inhibit adult human skin fibroblast proliferation and migration speed and is associated with increased reactive oxygen species (ROS) generation in a dose-dependent manner. In addition, resveratrol possesses potent intracellular antioxidative effects on ROS-free radicals in human skin fibroblasts. The authors studied the effects on migration speed as a surrogate to measure LED-BL effects on fibroblast function. The authors hypothesized that resveratrol, a potent scavenger of ROS, could prevent the effects of LED-BL on fibroblast migration speed. This would implicate ROS as the mechanistic driver of LED-BL effects on human skin fibroblasts. To demonstrate that resveratrol could prevent the effects of LED-BL (415-nm), fibroblasts were incubated with resveratrol (Sigma-Aldrich, St. Louis, MO) at concentrations of 0.001% and 0.0001% for 24 hours and then irradiated with LED-BL at fluences of 30, 45, and 80 J/cm. Postirradiation fibroblast migratory speed was assayed in an environment-controlled computer-assisted video microscopy system. Reactive oxygen species levels were measured by flow cytometric analysis of dihydrorhodamine. Statistical analyses with analysis of variance and Student t-test were performed to compare individual treatment arms and matched controls. The experimental results demonstrate that pretreatment of skin fibroblasts with resveratrol at concentrations of 0.001% and 0.0001% prevents the effects of 30, 45, and 80 J/cm of LED-BL on fibroblast migration speed. The authors found that LED-BL at a fluences of 30, 45, and 80 J/cm significantly increased ROS, whereas pretreatment with 0.001% resveratrol significantly reduced ROS generation. The findings demonstrate that LED-BL-induced decreases in fibroblast migration speed can be prevented by pretreating cells with resveratrol. This finding supports the hypothesis that ROS generation is the most likely driver of LED-BL-induced alterations in migration speed and suggests that ROS generation may be responsible for a number of other alterations seen after LED-BL Phototherapy, such as decreases in cellular migration, cytokine levels, and myofibroblast differentiation. The authors hypothesize that their findings may result in greater understanding of the fundamental mechanisms underlying visible light interaction with skin and they hope dermatologists and other researchers may use these pathways for patient benefit.
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Resveratrol Prevents High Fluence Red Light-Emitting Diode Reactive Oxygen Species-Mediated Photoinhibition of Human Skin Fibroblast Migration.
PloS one, 2015Co-Authors: Andrew Mamalis, Eugene Koo, Roslyn Rivkah Isseroff, William J. Murphy, Jared JagdeoAbstract:Skin fibrosis is a significant medical problem that leads to a functional, aesthetic, and psychosocial impact on quality-of-life. Light-emitting diode-generated 633-nm red light (LED-RL) is part of the visible light spectrum that is not known to cause DNA damage and is considered a safe, non-invasive, inexpensive, and portable potential alternative to Ultraviolet Phototherapy that may change the treatment paradigm of fibrotic skin disease. The goal of our study was to investigate the how reactive oxygen species (ROS) free radicals generated by high fluence LED-RL inhibit the migration of skin fibroblasts, the main cell type involved in skin fibrosis. Fibroblast migration speed is increased in skin fibrosis, and we studied cellular migration speed of cultured human skin fibroblasts as a surrogate measure of high fluence LED-RL effect on fibroblast function. To ascertain the inhibitory role of LED-RL generated ROS on migration speed, we hypothesized that resveratrol, a potent antioxidant, could prevent the photoinhibitory effects of high fluence LED-RL on fibroblast migration speed. High fluence LED-RL generated ROS were measured by flow cytometry analysis using dihydrorhodamine (DHR). For purposes of comparison, we assessed the effects of ROS generated by hydrogen peroxide (H2O2) on fibroblast migration speed and the ability of resveratrol, a well known antioxidant, to prevent LED-RL and H2O2 generated ROS-associated changes in fibroblast migration speed. To determine whether resveratrol could prevent the high fluence LED-RL ROS-mediated photoinhibition of human skin fibroblast migration, treated cells were incubated with resveratrol at concentrations of 0.0001% and 0.001% for 24 hours, irradiated with high fluences LED-RL of 480, 640, and 800 J/cm2. High fluence LED-RL increases intracellular fibroblast ROS and decreases fibroblast migration speed. LED-RL at 480, 640 and 800 J/cm2 increased ROS levels to 132.8%, 151.0%, and 158.4% relative to matched controls, respectively. These LED-RL associated increases in ROS were prevented by pretreating cells with 0.0001% or 0.001% resveratrol. Next, we quantified the effect of hydrogen peroxide (H2O2)-associated ROS on fibroblast migration speed, and found that while H2O2-associated ROS significantly decreased relative fibroblast migration speed, pretreatment with 0.0001% or 0.001% resveratrol significantly prevented the decreases in migration speed. Furthermore, we found that LED-RL at 480, 640 and 800 J/cm2 decreased fibroblast migration speed to 83.0%, 74.4%, and 68.6% relative to matched controls, respectively. We hypothesized that these decreases in fibroblast migration speed were due to associated increases in ROS generation. Pretreatment with 0.0001% and 0.001% resveratrol prevented the LED-RL associated decreases in migration speed. High fluence LED-RL increases ROS and is associated with decreased fibroblast migration speed. We provide mechanistic support that the decreased migration speed associated with high fluence LED-RL is mediated by ROS, by demonstrating that resveratrol prevents high fluence LED-RL associated migration speed change. These data lend support to an increasing scientific body of evidence that high fluence LED-RL has anti-fibrotic properties. We hypothesize that our findings may result in a greater understanding of the fundamental mechanisms underlying visible light interaction with skin and we anticipate clinicians and other researchers may utilize these pathways for patient benefit.
Kenneth A. Arndt - One of the best experts on this subject based on the ideXlab platform.
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Ultraviolet Phototherapy of uremic pruritus
Annals of Internal Medicine, 2020Co-Authors: Barbara A. Gilchrest, John W. Rowe, Robert S. Brown, Theodore I. Steinman, Kenneth A. ArndtAbstract:Abstract The beneficial effect of sunburn-spectrum Ultraviolet (UVB) Phototherapy on uremic pruritus was studied. Seven patients were treated twice weekly for 4 weeks with UVB to one half of the bo...
