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      Biology of Lymphedema

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          Abstract

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          Lymphedema is a chronic, debilitating disease of the lymphatic vasculature. Although several reviews focus on the anatomy and physiology of the lymphatic system, this review provides an overview of the lymphatic vasculature and, moreover, of lymphatic system dysfunction and lymphedema. Further, we aim at advancing the knowledge in the area of lymphatic system function and how dysfunction of the lymphatic system—as seen in lymphedema—affects physiological systems, such as the cardiovascular system, and how those might be modulated by lymphedema therapy.

          Abstract

          This narrative review portrays the lymphatic system, a poorly understood but important physiological system. While several reviews have been published that are related to the biology of the lymphatic system and lymphedema, the physiological alternations, which arise due to disturbances of this system, and during lymphedema therapy, are poorly understood and, consequently, not widely reported. We present an inclusive collection of evidence from the scientific literature reflecting important developments in lymphedema research over the last few decades. This review aims at advancing the knowledge on the area of lymphatic system function as well as how system dysfunction, as seen in lymphedema, affects physiological systems and how lymphedema therapy modulates these mechanisms. We propose that future studies should aim at investigating, in-detail, aspects that are related to fluid regulation, hemodynamic responses, and endothelial and/or vascular changes due to lymphedema and lymphedema therapy.

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          Most cited references180

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          Prediction of blood volume in normal human adults.

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            A multifactorial intervention to reduce the risk of falling among elderly people living in the community.

            Since falling is associated with serious morbidity among elderly people, we investigated whether the risk of falling could be reduced by modifying known risk factors. We studied 301 men and women living in the community who were at least 70 years of age and who had at least one of the following risk factors for falling: postural hypotension; use of sedatives; use of at least four prescription medications; and impairment in arm or leg strength or range of motion, balance, ability to move safely from bed to chair or to the bathtub or toilet (transfer skills), or gait. These subjects were given either a combination of adjustment in their medications, behavioral instructions, and exercise programs aimed at modifying their risk factors (intervention group, 153 subjects) or usual health care plus social visits (control group, 148 subjects). During one year of follow-up, 35 percent of the intervention group fell, as compared with 47 percent of the control group (P = 0.04). The adjusted incidence-rate ratio for falling in the intervention group as compared with the control group was 0.69 (95 percent confidence interval, 0.52 to 0.90). Among the subjects who had a particular risk factor at base line, a smaller percentage of those in the intervention group than of those in the control group still had the risk factor at the time of reassessment, as follows: at least four prescription medications, 63 percent versus 86 percent, P = 0.009; balance impairment, 21 percent versus 46 percent, P = 0.001; impairment in toilet-transfer skills, 49 percent versus 65 percent, P = 0.05; and gait impairment, 45 percent versus 62 percent, P = 0.07. The multiple-risk-factor intervention strategy resulted in a significant reduction in the risk of falling among elderly persons in the community. In addition, the proportion of persons who had the targeted risk factors for falling was reduced in the intervention group, as compared with the control group. Thus, risk-factor modification may partially explain the reduction in the risk of falling.
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              Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans

              Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease (CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Biology (Basel)
                Biology (Basel)
                biology
                Biology
                MDPI
                2079-7737
                25 March 2021
                April 2021
                : 10
                : 4
                : 261
                Affiliations
                [1 ]Gravitational Physiology and Medicine Research Unit, Division of Physiology, Otto Loewi Research Center, Medical University of Graz, 3810 Graz, Austria; bianca.brix@ 123456medunigraz.at (B.B.); andreas.roessler@ 123456medunigraz.at (A.R.)
                [2 ]Faculty of Science, Masaryk University, Kotlářská 2, 61137 Brno, Czech Republic; omarsery@ 123456sci.muni.cz
                [3 ]Linfamed, 33100 Udine, Italy; a.onorato@ 123456linfamed.it
                [4 ]Wolfsberg Clinical Center for Lymphatic Disorders, Wolfsberg State Hospital, KABEG, 9400 Wolfsberg, Austria; christian.ure@ 123456kabeg.at
                Author notes
                [* ]Correspondence: nandu.goswami@ 123456medunigraz.at ; Tel.: +43-316-385-73852
                Author information
                https://orcid.org/0000-0002-7308-5450
                https://orcid.org/0000-0001-7126-4976
                https://orcid.org/0000-0002-6704-0723
                Article
                biology-10-00261
                10.3390/biology10040261
                8065876
                33806183
                22e01bfe-af29-4ce3-90b3-243b42371be6
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 February 2021
                : 23 March 2021
                Categories
                Review

                lymphatic vasculature,lymphedema,complete decongestive therapy,manual lymphatic drainage,cardiovascular system,hemodynamics,fluid shifts,perometry,plasma volume

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