The lymphatic vasculature comprises an intricate network of vessels critical for fluid homeostasis, immune surveillance and fat absorption. Recent studies have provided insights into the developmental processes and molecular mechanisms controlling the formation and remodelling of the lymphatic vessels. These studies have further demonstrated the essential and active role of the lymphatic vessels in various pathological conditions and advanced our understanding of the progression of human diseases, such as inflammation and tumorigenesis. In the context of the latest exciting findings, we (...) review here the current understanding of the mechanisms of lymphatic development and contribution of lymphatic vessels to pathological conditions. BioEssays 29:1192–1202, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

A striking and unexplained feature of granulomatous inflammation is its anatomical association with the lymphatic system. Accumulating evidence suggests that lymphatic tracks and granulomas may alter the function of each other. The formation of new lymphatics, or lymphangiogenesis, is an adaptive response to tumor formation, infection, and wound healing. Granulomas also may induce lymphangiogenesis which, through a variety of mechanisms, could contribute to disease outcomes in tuberculosis and sarcoidosis. On the other hand, alterations in lymph node function and lymphatic (...) draining may be primary events which attenuate the risk and severity of granulomatous inflammation. This review begins with an introduction of granulomatous inflammation and the lymphatic system. A role of the lymphatic system in tuberculosis and sarcoidosis is then hypothesized. With a focus on lymphangiogenesis in these diseases, and on the potential for this process to promote dissemination, parallels are established with the well‐established role of lymphangiogenesis in tumor biology. (shrink)

SummaryThis article documents understandings and responses to mass drug administration for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of people living at these highly endemic locations either did not receive or actively rejected (...) free treatment. A combination of social, economic and political reasons explain the low uptake of drugs. These include a fear of treatment ; divergence between biomedical and local understandings of lymphatic filariasis; and limited and ineffective communication about the rationale for mass treatment. Other contributory factors are the reliance upon volunteers for distribution within villages and, in some locations, strained relationships between different groups of people within villages as well as between local leaders and government officials. The article also highlights a disjuncture between self-reported uptake of drugs by adults at a village level and the higher uptake of drugs recorded in official reports. The latter informs claims that elimination will be a possibility by 2020. This gives voice to a broader problem: there is considerable pressure for those implementing MDA to report positive results. The very real challenges of making MDA work are pushed to one side – adding to a rhetoric of success at the expense of engaging with local realities. It is vital to address the kind of issues raised in this article if current attempts to eliminate lymphatic filariasis in mainland coastal Tanzania are to achieve their goal. (shrink)

This manuscript considers the transmission dynamics of lymphatic filariasis with some intervention strategies in place. Unlike previously developed models, our model takes into account both the exposed and infected classes in both the human and mosquito populations, respectively. We also consider vaccinated, treated and recovered humans in the presented model. The global dynamics of the proposed model are completely determined by the basic and effective reproduction numbers. We then use Lyapunov function theory to find the sufficient conditions for global stability (...) of both the disease-free equilibrium and endemic equilibrium. The Lyapunov functions show that when the basic reproduction number is less than or equal to unity, the disease-free equilibrium is globally asymptotically stable, and when it is greater than unity then the endemic equilibrium is also globally asymptotically stable. Finally, numerical simulations are carried out to investigate the effects of the intervention strategies and key parameters to the spread of lymphatic filariasis. The numerical simulations support the analytical results and illustrate possible model behavioral scenarios. (shrink)

This book provides a comprehensive account of vascular biology and pathology and its significance for health and disease. It systematically and chronologically explains how we came to our current understanding of the vasculature and it's function today, and describes in an entertaining way the diverse flaws and turns in science and medicine from the past. It thereby offers a complete and well-studied history on vascular biology and medicine. The book has an easy-to-read style and is written for students as well (...) as scientists, physicians and lecturers in the field of biomedicine, human physiology, cardiology and hematology. (shrink)

Lymphangiogenesis is an important developmental process that is critical to regulation of fluid homeostasis, immune surveillance and response as well as pathogenesis of a number of diseases, among them cancer, inflammation, and heart failure. Specification, formation, and maturation of lymphatic blood vessels involves an interplay between a series of events orchestrated by various transcription factors that determine expression of key genes involved in lymphangiogenesis. These are traditionally thought to be under control of several key growth factors including vascular growth factor‐C (...) (VEGF‐C) and fibroblast growth factors (FGFs). Recent insights into VEGF and FGF signaling point to their role in control of endothelial metabolic processes such as glycolysis and fatty acid oxidation that, in turn, play a major role in regulation of lymphangiogenesis. These advances have significantly increased our understanding of lymphatic biology and opened new therapeutic vistas. Here we review our current understanding of metabolic controls in the lymphatic vasculature. (shrink)

The lymphatic vasculature plays a critical role in the regulation of body fluid volume and immune function. Extensive research into the molecular mechanisms that control blood vessel growth has led to identification of molecules that also regulate development and growth of the lymphatic vessels. This is generating a great deal of interest in the molecular control of the lymphatics in the context of embryogenesis, lymphatic disorders and tumor metastasis. Studies in animal models carried out over the past three years (...) have shown that the soluble protein growth factors, vascular endothelial growth factor (VEGF)‐C and VEGF‐D, and their cognate receptor tyrosine kinase, VEGF receptor‐3 (VEGFR‐3), are critical regulators of lymphangiogenesis. Furthermore, disfunction of VEGFR‐3 has recently been shown to cause lymphedema. The capacity to induce lymphangiogenesis by manipulation of the VEGF‐C/VEGF‐D/VEGFR‐3 signaling pathway offers new opportunities to understand the function of the lymphatic system and to develop novel treatments for lymphatic disorders. BioEssays 24:1030–1040, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Importance Informed consent is essential to ethical, rigorous research and is important to recruitment and retention in cancer trials.Objective To examine cancer clinical trial (CCT) participants’ perceptions of informed consent processes and variations in perceptions by cancer type.Design and Setting and Participants Cross-sectional survey from mixed-methods study at National Cancer Institute–designated Northeast comprehensive cancer center. Open-ended and forced-choice items addressed: (1) enrollment and informed consent experiences and (2) decision-making processes, including risk-benefit assessment. Eligibility: CCT participant with gastro-intestinal or genitourinary, hematologic-lymphatic (...) malignancies, lung cancer, and breast or gynecological cancer (N = 334).Main Outcome Measures Percentages satisfied with consent process and information provided; and assessing participation’s perceptions of risks/benefits. Multivariable logistic or ordinal regression examined differences by cancer type.Results Most patient-participants felt well informed by the consent process (more than 90% overall and by cancer type) and. most (87.4%) reported that the consent form provided all the information they wanted, although nearly half (44.8%) reported that they read the form somewhat carefully or less. More than half (57.9%) said that talking to research staff (i.e., the consent process) had a greater impact on participation decisions than reading the consent form (2.1%). A third (31.1%) were very sure of joining in research studies before the informed consent process (almost half of lung cancer patients did—47.1%). Most patients personally assessed the risks and benefits before consenting. However, trust in physicians played an important role in the decision to enroll in CCT.Conclusions and Relevance Cancer patients rely less on written features of the informed consent process than on information obtained from the research staff and their own physicians. Research should focus on information and communication strategies that support informed consent from referring physicians, researchers, and others to improve patient risk-benefit assessment and decision-making. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:I am Not Obese. I am Just Fat.Sarah BrambletteMy body mass index classifies me as super morbidly obese, however my overall vital health statistics would indicate otherwise. I celebrated the American Medical Association’s classification of obesity as a disease for several reasons. First, obesity as a disease involves other medical complications of which I have none, so finally perhaps I can say I am not obese, I am just (...) fat. I am fat, as in my weight is caused by Lipedema and Lymphedema. Lipedema is a congenital condition, which causes my body to produce and accumulate abnormal amounts of adipose tissue in my legs, hips, thighs, and arms. There is not much known about Lipedema in the medical profession, even though it was identified in 1940 by doctors at the Mayo Clinic, and not many treatment options exist. Abnormal Lipedema tissue does not respond to restrictive caloric diet or exercise. Lymphedema is a condition of localized fluid retention and tissue swelling caused by a compromised lymphatic system. The second reason I celebrated obesity being classified as a disease was the hope that more research would be conducted on the actual causes and treatment of obesity and that research might include adipose tissue disorders. My vital health statistics are all normal, yet I still face challenges getting proper treatment in healthcare.My StoryAs I sat staring at the metal beast, I decided to make one final attempt to mount it. I placed my right foot on the step and used both hands to boost myself up, my lower legs were so large there was no room for my left foot. Immediately the exam table began to tip towards me, then slammed loudly against the tile floor as I quickly stepped off. It was a game of exam table teeter–totter I had played many times before and lost more often than won. I gave up, placed the sheet meant to cover my legs on the chair in the corner and squeezed myself down between its arms. The exam gown pinched my arms, barely covering the front of me and draped over my legs.My LegsOne of the main reasons I was seeing a new doctor, my first doctor visit in several years. My previous family doctor had retired. I was not ill, I was concerned. My weight had reached a point to where I was scared for my health and I wanted to get help and answers. I wanted answers about why my legs were so large and leaked fluid.The answer I got was one I had heard before “It’s your weight”.To the doctor’s credit, she did explain it a bit more, she said the fluid in my legs was due to my excess weight putting pressure on my legs. However, she did not actually know how much I weighed. The scale in her office only went to 350lbs, and even with the add–on weight it could not register a weight for me, so we only knew I weighed more than 400lbs. I asked her if she knew if the hospital or another office had a scale that could weigh me. She did not. She may have sent me home with a prescription for a diuretic, I do not remember. I know I was not sent home with any help for my weight or my legs, just a follow–up appointment. It was during that follow up appointment that I advocated for myself and asked if she would refer me for physical therapy, so that I could do some safe and monitored exercise. She agreed, and I began physical therapy in the pool.At the pool I met other people who looked similar to my size. I noticed their legs were normal size and wondered why? Then I thought about sumo wrestlers. Sumo wrestlers weigh hundreds of pounds and their legs are normal too. What was wrong with my legs? One day I heard a man in the pool tell another [End Page 85] patient that he had lost weight. I wondered where he was able to weigh himself, and hoped it was not rude to ask him. He told me... (shrink)

The autosomal recessive genetic disorder, Nijmegen Breakage Syndrome, is characterised by an excessively high risk for the development of lymphatic tumours and an extreme sensitivity towards ionising radiation. The most likely explanation for these characteristics, a deficiency in the repair of DNA lesions, has been greatly substantiated by the recent cloning of the gene mutated in Nijmegen Breakage Syndrome patients and the analysis of its protein product, nibrin. The direct involvement of this protein in the processing of DNA double strand (...) breaks caused by ionising radiation and those also necessary for normal DNA metabolism can be correlated with many of the cellular and clinical aspects of the disease, including the cancer predisposition of patients and their heterozygous relatives. BioEssays 21:649–656, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Narrative medicine explores the stories that patients tell; this paper, conversely, looks at some of the stories that patients are told. The paper starts by examining the ‘story’ told by the Shambaa people of Tanzania to explain the bubonic plague and contrasts this with the stories told by Ghanaian communities to explain lymphatic filariasis. By harnessing insights from memory studies, these stories’ memorability is claimed to be due to their use mnemonic devices woven into stories. The paper suggests that stories (...) can be unpatronising, informative, and appropriate vehicles for communicating medical information to all age groups across all cultures. (shrink)

The establishment of distinct cellular identities was pivotal during the evolution of Metazoa, enabling the emergence of an array of specialized tissues with different functions. In most animals including vertebrates, cell specialization occurs in response to a combination of intrinsic (e.g., cellular ontogeny) and extrinsic (e.g., local environment) factors that drive the acquisition of unique characteristics at the single‐cell level. The first functional organ system to form in vertebrates is the cardiovascular system, which is lined by a network of endothelial (...) cells whose organ‐specific characteristics have long been recognized. Recent genetic analyses at the single‐cell level have revealed that heterogeneity exists not only at the organ level but also between neighboring endothelial cells. Thus, how endothelial heterogeneity is established has become a key question in vascular biology. Drawing upon evidence from multiple organ systems, here we will discuss the role that lineage history may play in establishing endothelial heterogeneity. (shrink)