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Journal articles on the topic 'Lymphatic System Disorders'
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1
Patil, A. R., S. Nandikoor, J. De Marco, R. Bhat, S. Shivakumar, and G. Mallrajapatna. "Disorders of the lymphatic system of the abdomen." Clinical Radiology 71, no. 10 (October 2016): 941–52. http://dx.doi.org/10.1016/j.crad.2016.06.116.
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Lee, Shimwoo, Aarti P. Luhar, Edward Wolfgang Lee, Sanjay Sinha, and Ravi N. Srinivasa. "Pediatric Lymphangiography: Imaging to Intervention." Digestive Disease Interventions 03, no. 03 (August 22, 2019): 203–13. http://dx.doi.org/10.1055/s-0039-1693414.
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AbstractThe lymphatic system plays a crucial role in fluid transport as well as facilitating immune recognition. Disruption of lymphatic flow can lead to significant morbidity and mortality in the pediatric population, manifesting as lymphatic malformations and lymphatic leaks. There has been rising interest in developing minimally invasive image-guided approaches to diagnose and treat lymphatic disorders in pediatric patients. Notably, magnetic resonance imaging of the lymphatic system has emerged as a promising diagnostic tool. Moreover, interventions such as sclerotherapy and thoracic duct embolization for treatment of lymphatic malformations and leaks have come forth as safe and effective alternatives to surgery. The aim of this article is to review various pediatric lymphatic disorders and discuss advances in image-guided diagnostic and therapeutic options for these entities.
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Hsu, M., and M. Itkin. "Lymphatic system flow disorders: novel imaging and interventional techniques." Journal of Vascular and Interventional Radiology 27, no. 3 (March 2016): S264. http://dx.doi.org/10.1016/j.jvir.2015.12.671.
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Patel, P. A., and A. M. Barnacle. "Re: Disorders of the lymphatic system of the abdomen." Clinical Radiology 72, no. 1 (January 2017): 91–92. http://dx.doi.org/10.1016/j.crad.2016.10.013.
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Yankova, G. S., and O. B. Bogomyakova. "Brain lymphatic drainage system – visualization opportunities and current state of the art." Complex Issues of Cardiovascular Diseases 9, no. 3 (September 28, 2020): 81–89. http://dx.doi.org/10.17802/2306-1278-2020-9-3-81-89.
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The lymphatic drainage system of the brain is assumed to consist of the lymphatic system and a network of meningeal lymphatic vessels. This system supports brain homeostasis, participates in immune surveillance and presents a new therapeutic target in the treatment of neurological disorders.The article analyzes and systematizes data on the brain lymphatic drainage system. The key components of this system are considered: recently described meningeal lymphatic vessels and their relationship with the glymphatic system, which provides perfusion of the central nervous system with cerebrospinal and interstitial fluids. The lymphatic drainage system helps to maintain water and ion balances of the interstitial fluid and to remove metabolic waste products, assists in reabsorption of macromolecules. Disorders in its work play a crucial role in age-related changes in the brain, the pathogenesis of neurovascular and neurodegenerative diseases, as well as injuries and brain tumors. The review also presents the results of human studies concerning the presence, anatomy and structure of meningeal lymphatic vessels and the glymphatic system. The discovery of the brain lymphatic drainage system has not only changed our understanding of cerebrospinal fluid circulation, but also contributed to understanding the pathology and mechanisms of neurodegenerative diseases.
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Patil, A. R. "Re: Disorders of the lymphatic system of the abdomen. A reply." Clinical Radiology 72, no. 1 (January 2017): 92. http://dx.doi.org/10.1016/j.crad.2016.10.012.
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Si, Hongjiang, Jian Wang, Cynthia J. Meininger, Xu Peng, David C. Zawieja, and Shenyuan L. Zhang. "Ca2+ release-activated Ca2+ channels are responsible for histamine-induced Ca2+ entry, permeability increase, and interleukin synthesis in lymphatic endothelial cells." American Journal of Physiology-Heart and Circulatory Physiology 318, no. 5 (May 1, 2020): H1283—H1295. http://dx.doi.org/10.1152/ajpheart.00544.2019.
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The lymphatic functions in maintaining lymph transport, and immune surveillance can be impaired by infections and inflammation, thereby causing debilitating disorders, such as lymphedema and inflammatory bowel disease. Histamine is a key inflammatory mediator known to trigger vasodilation and vessel hyperpermeability upon binding to its receptors and evoking intracellular Ca2+ ([Ca2+]i) dynamics for downstream signal transductions. However, the exact molecular mechanisms beneath the [Ca2+]i dynamics and the downstream cellular effects have not been elucidated in the lymphatic system. Here, we show that Ca2+ release-activated Ca2+ (CRAC) channels, formed by Orai1 and stromal interaction molecule 1 (STIM1) proteins, are required for the histamine-elicited Ca2+ signaling in human dermal lymphatic endothelial cells (HDLECs). Blockers or antagonists against CRAC channels, phospholipase C, and H1R receptors can all significantly diminish the histamine-evoked [Ca2+]i dynamics in lymphatic endothelial cells (LECs), while short interfering RNA-mediated knockdown of endogenous Orai1 or STIM1 also abolished the Ca2+ entry upon histamine stimulation in LECs. Furthermore, we find that histamine compromises the lymphatic endothelial barrier function by increasing the intercellular permeability and disrupting vascular endothelial-cadherin integrity, which is remarkably attenuated by CRAC channel blockers. Additionally, the upregulated expression of inflammatory cytokines, IL-6 and IL-8, after histamine stimulation was abolished by silencing Orai1 or STIM1 with RNAi in LECs. Taken together, our data demonstrated the essential role of CRAC channels in mediating the [Ca2+]i signaling and downstream endothelial barrier and inflammatory functions induced by histamine in the LECs, suggesting a promising potential to relieve histamine-triggered vascular leakage and inflammatory disorders in the lymphatics by targeting CRAC channel functions.
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Zulkharnain Tousheed, Syed. "Immune Response In Various Diffuse Parenchymal Lung Disorders (DPLDs)." Pulmonary Medicine and Respiratory Research 7, no. 3 (November 3, 2020): 1–8. http://dx.doi.org/10.24966/pmrr-0177/100046.
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Lung has one of the largest surface areas. It has to bear the brunt of infinite insults both from the airway and vascular end. The inhaled particles depending upon the size are cleared either by the luminal or the alveolar or the interstitial macrophages. The alveolar and interstitial macrophages clear the engulfed particles via the lymphatic system, which depends upon the blood perfusion. Most of the particles from the lower and middle lobes are cleared successfully, but the particle engulfed by macrophages in the upper lobe get trapped in the interstitium because of poor lymphatic supply.
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Burgard, C., R. Baumeister, F. Strobl, A. Rominger, P. Bartenstein, J. Wallmichrath, A. Frick, M. Notohamiprodjo, and M. Weiss. "Magnetic resonance imaging versus lymphoscintigraphy for the assessment of focal lymphatic transport disorders of the lower limb." Nuklearmedizin 53, no. 05 (2014): 190–96. http://dx.doi.org/10.3413/nukmed-0649-14-03.
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SummaryPurpose: To compare the diagnostic accuracy of magnetic resonance imaging (MR-lym- phangiography) and lymphoscintigraphy for assessment of focal lesions of the peripheral lymphatic system. Patients with focal lymphatic transport disorders might benefit from surgi-cal interventions. Patients, methods: We examined by lymphoscintigraphy and MR- lymphangiography a total of 85 lower limbs in 46 consecutive patients (33 women; mean age 41 years; range 9-79 years) presenting with uni- or bilateral lymphedema. MR-lym- phangiographies were obtained at isotropic sub-millimeter resolution with a 3.0 Tesla magnet after injection of gadolinium contrast medium. MR-lymphangiography was reviewed by radiologists, whereas lymp- hoscintigraphy was reviewed by nuclear medicine physicians. The images were examined for localization and distribution of any focal lesions of the lymphatic vessel system. Diagnostic accuracy of the MR-approach was calculated relative to the lymphoscintigraphy gold standard. Results: There was substantial correlation of results by the two modalities (κ = 0.62). MR-lymphangiography had sensitivity of 68%, specificity of 91%, positive predictive value of 82%, and negative predictive value of 83%. Conclusions: Imaging findings of both lymphoscintigraphy and MR-lymph- angiography showed good diagnostic accuracy. MR-lymphangiography proved more information about anatomic location of focal lesions of the lymphatic vessels, but use of MR-lymphangiography is currently constrained due to the requirement for off-label subcutaneous injection of gadolinium che- lates. Consequently, and due to its superior sensitivity lymphoscintigraphy remains the most common imaging method to assess functional lymphatic disorders of the lower limb.
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Korneva, Yu S., and R. V. Ukrainets. "The role of the cardiac lymphatic system in the development and progression of heart failure and novel therapeutic approaches for its management in post-infarction cardiac remodeling." Cardiovascular Therapy and Prevention 19, no. 3 (July 3, 2020): 2281. http://dx.doi.org/10.15829/1728-8800-2020-2281.
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Cardiac lymphatic vessels play a vital role in maintaining homeostasis in both physiological and pathological conditions, providing outflow of metabolites. It has been shown that myocardial infarction and postinfarction cardiac remodeling is accompanied by the lymphatic remodeling, which entails functional disorders and is of great importance in heart failure pathogenesis. As a result of progressive myocardial edema, hypoxia and fibrosis of the interstitial space increase, aggravating edema. Other pathways of additional myocardial damage and contractility reduction are triggered. Lymphatic efflux is associated with arrhythmias. Experimental models showed the positive effect of exogenous activation of lymphangiogenesis in relation to the prevention and treatment of heart failure, which can be further used to improve treatment regimens. This review discusses cardiac lymphatic remodeling after myocardial infarction, as well as the pathogenesis of related complications.
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Xie, Cheng, Catriona Stoddart, Anthony McIntyre, Victoria StNoble, Heiko Peschl, and Rachel Benamore. "A case series of thoracic dynamic contrast-enhanced MR lymphangiography: technique and applications." BJR|case reports 6, no. 3 (September 2020): 20200026. http://dx.doi.org/10.1259/bjrcr.20200026.
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Dynamic contrast-enhanced magnetic resonance lymphangiography is a radiation-free, high spatial resolution technique which is increasingly used to evaluate thoracic lymphatic disorders and for pre-procedural planning. DCE has the added advantage of allowing dynamic real-time evaluation of lymphatic flow. It can be employed to investigate commonly encountered clinical situations such as recurrent pleural effusions following trauma, thoracic duct injury after thoracic surgery, and exclude diseases and congenital malformations of the thoracic lymphatic system. The imaging procedure and protocol are detailed in this case series to highlight the application of dynamic contrast-enhanced magnetic resonance lymphangiography in everyday practice and its importance to guide surgical planning.
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Ogino, Ryohei, Kenji Hayashida, Sho Yamakawa, and Eishin Morita. "Adipose-Derived Stem Cells Promote Intussusceptive Lymphangiogenesis by Restricting Dermal Fibrosis in Irradiated Tissue of Mice." International Journal of Molecular Sciences 21, no. 11 (May 29, 2020): 3885. http://dx.doi.org/10.3390/ijms21113885.
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Currently, there is no definitive treatment for lymphatic disorders. Adipose-derived stem cells (ADSCs) have been reported to promote lymphatic regeneration in lymphedema models, but the mechanisms underlying the therapeutic effects remain unclear. Here, we tested the therapeutic effects of ADSC transplantation on lymphedema using a secondary lymphedema mouse model. The model was established in C57BL/6J mice by x-irradiation and surgical removal of the lymphatic system in situ. The number of lymphatic vessels with anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunoreactivity increased significantly in mice subjected to transplantation of 7.5 × 105 ADSCs. X-irradiation suppressed lymphatic vessel dilation, which ADSC transplantation could mitigate. Proliferative cell nuclear antigen staining showed increased lymphatic endothelial cell (LEC) and extracellular matrix proliferation. Picrosirius red staining revealed normal collagen fiber orientation in the dermal tissue after ADSC transplantation. These therapeutic effects were not related to vascular endothelial growth factor (VEGF)-C expression. Scanning electron microscopy revealed structures similar to the intraluminal pillar during intussusceptive angiogenesis on the inside of dilated lymphatic vessels. We predicted that intussusceptive lymphangiogenesis occurred in lymphedema. Our findings indicate that ADSC transplantation contributes to lymphedema reduction by promoting LEC proliferation, improving fibrosis and dilation capacity of lymphatic vessels, and increasing the number of lymphatic vessels via intussusceptive lymphangiogenesis.
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Rehal, Sonia, Matthew Stephens, Simon Roizes, Shan Liao, and Pierre-Yves von der Weid. "Acute small intestinal inflammation results in persistent lymphatic alterations." American Journal of Physiology-Gastrointestinal and Liver Physiology 314, no. 3 (March 1, 2018): G408—G417. http://dx.doi.org/10.1152/ajpgi.00340.2017.
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Inflammatory bowel disease (IBD) has a complex pathophysiology with limited treatments. Structural and functional changes in the intestinal lymphatic system have been associated with the disease, with increased risk of IBD occurrence linked to a history of acute intestinal injury. To examine the potential role of the lymphatic system in inflammation recurrence, we evaluated morphological and functional changes in mouse mucosal and mesenteric lymphatic vessels, and within the mesenteric lymph nodes during acute ileitis caused by a 7-day treatment with dextran sodium sulfate (DSS). We monitored whether the changes persisted during a 14-day recovery period and determined their potential consequences on dendritic cell (DC) trafficking between the mucosa and lymphoid tissues. DSS administration was associated with marked lymphatic abnormalities and dysfunctions exemplified by lymphangiectasia and lymphangiogenesis in the ileal mucosa and mesentery, increased mesenteric lymphatic vessel leakage, and lymphadenopathy. Lymphangiogenesis and lymphadenopathy were still evident after recovery from intestinal inflammation and correlated with higher numbers of DCs in mucosal and lymphatic tissues. Specifically, a deficit in CD103+ DCs observed during acute DSS in the lamina propria was reversed and further enhanced during recovery. We concluded that an acute intestinal insult caused alterations of the mesenteric lymphatic system, including lymphangiogenesis, which persisted after resolution of inflammation. These morphological and functional changes could compromise DC function and movement, increasing susceptibility to further gastrointestinal disease. Elucidation of the changes in mesenteric and intestinal lymphatic function should offer key insights for new therapeutic strategies in gastrointestinal disorders such as IBD. NEW & NOTEWORTHY Lymphatic integrity plays a critical role in small intestinal homeostasis. Acute intestinal insult in a mouse model of acute ileitis causes morphological and functional changes in mesenteric and intestinal lymphatic vessels. While some of the changes significantly regressed during inflammation resolution, others persisted, including lymphangiogenesis and altered dendritic cell function and movement, potentially increasing susceptibility to the recurrence of gastrointestinal inflammation.
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Park, Mina, Jin Woo Kim, Sung Jun Ahn, Yoon Jin Cha, and Sang Hyun Suh. "Aging Is Positively Associated with Peri-Sinus Lymphatic Space Volume: Assessment Using 3T Black-Blood MRI." Journal of Clinical Medicine 9, no. 10 (October 19, 2020): 3353. http://dx.doi.org/10.3390/jcm9103353.
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Objectives: Aging is a major risk factor for many neurological disorders and is associated with dural lymphatic dysfunction. We sought to evaluate the association of aging with the volume of the peri-sinus lymphatic space using contrast-enhanced 3T T1-weighted black-blood magnetic resonance imaging (MRI). Methods: In this retrospective study, 165 presumed neurologically normal subjects underwent brain MRIs for cancer staging between April and November 2018. The parasagittal peri-sinus lymphatic space was evaluated using contrast-enhanced 3D T1-weighted black-blood MRIs, and volumes were measured with semiautomatic method. We compared the volumes of normalized peri-sinus lymphatic spaces between the elderly (≥65 years, n = 72) and non-elderly (n = 93) groups and performed multivariate logistic regression analyses to assess if aging is independently associated with the volume of normalized peri-sinus lymphatic spaces. Results: The normalized peri-sinus lymphatic space volume was significantly higher in the elderly than in the non-elderly (mean, 3323 ± 758.7 mL vs. 2968.7 ± 764.3 mL, p = 0.047). After adjusting the intracranial volume, age age was the strongest factor independently associated with peri-sinus lymphatic space volume (β coefficient, 28.4 (5.7–51.2), p = 0.015) followed by male sex (β coefficient, 672.4 (113.5–1230.8), p = 0.019). Conclusions: We found that the peri-sinus dural lymphatic space volume was higher in the elderly group than in the non-elderly group, and the increased peri-sinus lymphatic space was independently associated with aging. These findings indicate that the peri-sinus lymphatic space may be related with the aging process and lymphatic system dysfunction as well.
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Gordon, Kristiana, Ruth Varney, Vaughan Keeley, Katie Riches, Steve Jeffery, Malou Van Zanten, Peter Mortimer, Pia Ostergaard, and Sahar Mansour. "Update and audit of the St George’s classification algorithm of primary lymphatic anomalies: a clinical and molecular approach to diagnosis." Journal of Medical Genetics 57, no. 10 (May 14, 2020): 653–59. http://dx.doi.org/10.1136/jmedgenet-2019-106084.
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Primary lymphatic anomalies may present in a myriad of ways and are highly heterogenous. Careful consideration of the presentation can lead to an accurate clinical and/or molecular diagnosis which will assist with management. The most common presentation is lymphoedema, swelling resulting from failure of the peripheral lymphatic system. However, there may be internal lymphatic dysfunction, for example, chylous reflux, or lymphatic malformations, including the thorax or abdomen. A number of causal germline or postzygotic gene mutations have been discovered. Some through careful phenotyping and categorisation of the patients based on the St George’s classification pathway/algorithm. The St George’s classification algorithm is aimed at providing an accurate diagnosis for patients with lymphoedema based on age of onset, areas affected by swelling and associated clinical features. This has enabled the identification of new causative genes. This update brings the classification of primary lymphatic disorders in line with the International Society for the Study of Vascular Anomalies 2018 classification for vascular anomalies. The St George’s algorithm considers combined vascular malformations and primary lymphatic anomalies. It divides the types of primary lymphatic anomalies into lymphatic malformations and primary lymphoedema. It further divides the primary lymphoedema into syndromic, generalised lymphatic dysplasia with internal/systemic involvement, congenital-onset lymphoedema and late-onset lymphoedema. An audit and update of the algorithm has revealed where new genes have been discovered and that a molecular diagnosis was possible in 26% of all patients overall and 41% of those tested.
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Vardakis, John C., Dean Chou, Liwei Guo, and Yiannis Ventikos. "Exploring neurodegenerative disorders using a novel integrated model of cerebral transport: Initial results." Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine 234, no. 11 (October 20, 2020): 1223–34. http://dx.doi.org/10.1177/0954411920964630.
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The neurovascular unit (NVU) underlines the complex and symbiotic relationship between brain cells and the cerebral vasculature, and dictates the need to consider both neurodegenerative and cerebrovascular diseases under the same mechanistic umbrella. Importantly, unlike peripheral organs, the brain was thought not to contain a dedicated lymphatics system. The glymphatic system concept (a portmanteau of glia and lymphatic) has further emphasized the importance of cerebrospinal fluid transport and emphasized its role as a mechanism for waste removal from the central nervous system. In this work, we outline a novel multiporoelastic solver which is embedded within a high precision, subject specific workflow that allows for the co-existence of a multitude of interconnected compartments with varying properties (multiple-network poroelastic theory, or MPET), that allow for the physiologically accurate representation of perfused brain tissue. This novel numerical template is based on a six-compartment MPET system (6-MPET) and is implemented through an in-house finite element code. The latter utilises the specificity of a high throughput imaging pipeline (which has been extended to incorporate the regional variation of mechanical properties) and blood flow variability model developed as part of the VPH-DARE@IT research platform. To exemplify the capability of this large-scale consolidated pipeline, a cognitively healthy subject is used to acquire novel, biomechanistically inspired biomarkers relating to primary and derivative variables of the 6-MPET system. These biomarkers are shown to capture the sophisticated nature of the NVU and the glymphatic system, paving the way for a potential route in deconvoluting the complexity associated with the likely interdependence of neurodegenerative and cerebrovascular diseases. The present study is the first, to the best of our knowledge, that casts and implements the 6-MPET equations in a 3D anatomically accurate brain geometry.
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Lantis, John C., Christopher Barrett, Kara S. Couch, Suzie Ehmann, Emily Greenstein, Marta Ostler, and Anthony Tickner. "A dual compression system: preliminary clinical insights from the US." Journal of Wound Care 29, Sup9 (September 1, 2020): S29—S37. http://dx.doi.org/10.12968/jowc.2020.29.sup9.s29.
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There is growing evidence on an interconnection between the venous and lymphatic systems in venous leg ulceration, and the possible effects of prolonged oedema and lymphatic impairment in delayed wound healing. Compression therapy is a widely accepted treatment for venous and lymphatic disorders, as it decreases recurrence rates and prolongs the interval between recurrences. Compression bandages improve venous return, increase the volume and rate of venous flow, reduce oedema and stimulate anti-inflammatory processes. The pressure at the interface (IP) of the bandage and the skin is related to the elastic recoil of the product used and its resistance to expansion. The pressure difference between the IP in the supine and standing positions is called the static stiffness index (SSI). Elastic materials provide little resistance to muscle expansion during physical activity, resulting in small pressure differences between resting and activity, with an SSI <10mmHg. Stiff, inelastic materials with a stretch of <100% resist the increase of muscle volume during physical activity, producing higher peak pressures, an SSI of >10mmHg and a greater haemodynamic benefit than elastic systems. UrgoK2 is a novel dual-layer high-compression system consisting of an inelastic (short stretch) and elastic (long stretch) bandage, resulting in sustained tolerable resting pressure and elevated working pressures over extended wear times. It is indicated for the treatment of active venous leg ulcers and the reduction of chronic venous oedema. Each bandage layer has a visual aid to enable application at the correct pressure level. Published European studies have assessed this compression system, exploring its consistency of application, tolerability and efficacy. This article presents the first reports of health professionals' clinical experience of using the compression system in the US, where it has been recently launched. Initial feedback is promising.
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Davis, Jennifer A., Sharina Palencia Desai, and Saulius Sumanas. "ETS Transcription Factor Etsrp/Etv2 Is Required for Lymphangiogenesis in Zebrafish and Is a Potential Therapeutic Target in Lymphatic Disease." Blood 124, no. 21 (December 6, 2014): 2767. http://dx.doi.org/10.1182/blood.v124.21.2767.2767.
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Abstract Lymphangiogenesis is of great clinical interest because of its essential role in such pathologic settings as inflammation, vascular malformations, and tumor metastasis. Previous observational hurdles are now overcome by use of the optically clear and genetically modifiable zebrafish embryo, which provides a vertebrate model for understanding lymphangiogenesis and for revealing putative therapeutic targets for metastatic disease and vascular/lymphatic malformations that currently have no cure. We and others have previously demonstrated that an evolutionarily conserved ETS transcription factor Etv2 / Etsrp functions as a master regulator during embryonic vascular development. However, its role in lymphatic development is not defined. Here we performed conditional knockdown of Etv2 function using photoactivatable morpholinos (MO) in a zebrafish model system to test Etv2 requirement during lymphangiogenesis. Our data show that conditional Etv2 inhibition at 1-day-post-fertilization (dpf) resulted in specific defects in lymphatic development, while blood vessel formation was not affected. The major lymphatic vessel, the thoracic duct, was absent or discontinuous in Etv2-depleted embryos (Figure 1) and the lymphatic progenitors failed to migrate (Figure 2) in absence of Etv2 function. Expression of the lymphatic markers lyve1, prox1a and the major VegfC receptor VegfR3 was strongly down regulated in the conditional Etv2 MO knockdown embryos. We further show that Etv2 expression is enriched in the posterior cardinal vein where lymphangioblasts (lymphatic endothelial cell precursors) originate during lymphangiogenesis and that overexpression of Etv2 throughout blood vasculature perturbs lymphangiogenesis. We further show that in the absence of Etv2 function, lymphatic progenitors fail to respond to VegfC signaling. Our results suggest that Etv2 initiates lymphangiogenesis in part by regulating Vegf3 expression. These results argue that Etv2 is a novel critical factor during lymphatic development, and it may represent a new target for chemical modulation in multiple lymphatic disorders. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
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Tkachenko, P. I., S. O. Bilokon, N. M. Lokhmatova, N. M. Korotych, and Yu B. Lobach. "PECULIARITIES OF CHANGES IN LYMPH COMPOSITION IN DIFFERENT FORMS OF LYMPHADENITIS MAXILLOFACIAL AREA IN CHILDREN." Актуальні проблеми сучасної медицини: Вісник Української медичної стоматологічної академії 19, no. 1 (April 26, 2019): 119–23. http://dx.doi.org/10.31718/2077-1096.19.1.119.
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This literature review highlights the role of the immunocompetence of the lymph substance and the oral mucosa in various clinical forms of lymphadenitis of the maxillofacial area in children. The purpose of the work was to conduct a reflective analysis of the importance of their protective responses in the development of inflammation in regional lymph nodes. According to modern conceptions about the morpho-functional significance of the lymphatic system, it is considered first of all as one of the components of the body protective system, which is anatomically closely related to the vascular system and includes capillaries, lymphatic vessels, lymph nodes, trunks and ducts through which the lymph flows from organs and systems to the site of the merge of the internal jugular and subclavian veins. In response to entering foreign particles bearing signs of alienation into the body, lymphocytes and related antibodies are being produced in the organs of the lymphatic system and then are transferred to the site of injury through the lymphatic passageways, where the immune response takes place. The presence of a significant number of nosological forms of the disease, the factors contributing to the development of acute or chronic inflammation in the lymph nodes of the face and neck can be explained by the diversity of functions performed by them and the imperfect level of the development of structural elements of the immune system in children at the general and local levels. According to the fact that the oral mucous membrane is borderline anatomical substance through which the antigenic loading is directly carried out, it is its immunocompetence that can greatly affect on the high probability of the development of inflammatory processes of odontogenic and non-odontogenic origin. The lack of in-depth information about the multifactorial mechanisms of the aetiology and pathogenesis of lymphadenitis of the maxillofacial area of different genesis in children causes poses some difficulties in their understanding, especially in children with signs of the developmental disorders in the antenatal and early postnatal periods that influences ontogenesis, thus impacting the strength of the body systemic and local immune responses. Therefore, the study of the morphological and immunohistochemical architectonics of certain sections of the oral mucosa and regional lymphatic formations including investigation of the level of their nonspecific and specific protection is an important factor in substantiating the appropriateness to include immunocorrection medicines of different pharmacological actions into the integrated therapy.
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Tavarozzi, Rita, Enrica Manzato, and Anna Lombardi. "Lymph Node Ultrasound in Lymphoproliferative Disorders: Where Are We Now?" Journal of Clinical Imaging Science 11 (April 19, 2021): 22. http://dx.doi.org/10.25259/jcis_31_2021.
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Lymphoproliferative disorders are one of the most frequent hematological malignancies affecting the blood and lymphatic system. To better stratify patients, an accurate imaging evaluation is needed. Although computed tomography and positron emission tomography are considered the standard methods, these procedures have several clinical drawbacks, such as biological risk and high costs. Ultrasound (US) is a rapid and user-friendly method to evaluate lymph node (LN) and organ enlargements. US imaging provides more sensitive information about LN structure, vascularization, and metabolism and new techniques have increased its specificity, especially in malignant setting. However, validated and standardized criteria for its use are missing, with only several single-center experiences reported. Therefore, the aim of this paper is to review and briefly illustrate the status of the US knowledge and applications in lymphoproliferative workup, particularly concerning malignant LN pathology.
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Xu, Chongrui, Hai-Yan Tu, Yueli Sun, Yang-Si Li, Bingfei Xu, Binchao Wang, Hua-Jun Chen, et al. "Adverse events in non-small cell lung cancer patients receiving immune checkpoint inhibitors: A single center, real-world study in China." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e21081-e21081. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e21081.
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e21081 Background: Immune checkpoint inhibitors (ICIs) have improved clinical outcomes in non-small cell lung cancer (NSCLC), whereas they also can cause various adverse events (AEs). We reported the incidences, spectrum and severity of AEs in real-life practice after the approval of ICIs in Chinese NSCLC patients. Methods: In this single center, retrospective study, anonymized electronic medical record data were collected from the dedicated lung cancer immunotherapy outpatient clinic of Guangdong Provincial People’s Hospital through the LinkDoc database. The patients (≥18 years old) with pathologically diagnosed metastatic NSCLC who receiving ICIs between 1 June 2019 and 31 December 2020 were included. The immune-related adverse events (irAEs) were diagnosed and assessed by oncologists. All AEs were classified and graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE V5.0). Results: A total of 203 patients with a median age of 60.5 years were included in this study. Most patients were male (81.8%), smokers (49.8%), non-squamous histological type (51.7%). 61.1% of patients visited the outpatient clinic more than once. Pembrolizumab and Nivolumab were given to the majority of patients (80.8%). 114 patients (56.2%) received single-agent and 89 patients (43.8%) received combination therapy. The median duration of ICIs therapy was 271.2 days. In our study, 68.0% of patients experienced any-grade AEs, and 19.7% experienced grade≥3 AEs. The most commonly AEs were abnormal laboratory findings (57.1%), blood and lymphatic system disorders (25.1%), and respiratory disorders (19.7%). All of 93 patients (45.8%) experienced irAEs and 6 patients (8.4%) developed grade≥3 irAEs. The most frequent irAEs included blood and lymphatic system disorders (25.1%), hepatobiliary disorders (17.7%), and cardiac disorders (9.9%). Cough (3.4%), sputum (2.5%), and pain (2.0%) were the most frequent AEs which received treatment. Conclusions: Our results showed 68.0% and 45.8% patients experienced AEs and irAEs, respectively. The AEs and irAEs were primarily low grade. This study also demonstrated the information of AEs could be well collected and managed through our dedicated lung cancer immunotherapy outpatient clinic. [Table: see text]
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Apsangikar, Prasad, Sunil Chaudhry, Manoj Naik, and Parvez Kozgi. "A phase III, multicentric, open-label, two-arm, parallel group, active-control, randomized, comparative clinical study to evaluate efficacy and safety of RituxiRel™ arm (rituximab) with reference arm (rituximab) in patients with non-Hodgkin's lymphoma." Asian Journal of Oncology 03, no. 01 (January 2017): 017–22. http://dx.doi.org/10.4103/asjo.asjo_29_16.
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Abstract Introduction: Non-Hodgkin's lymphoma (NHL) is the sixth most common hematological malignancy in adults, with B-cell lymphomas accounting for 85% of all NHLs. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL and follicular lymphoma (FL) is the second most common form of B-cell NHL. Materials and Methods: The primary objective of this study is to assess the efficacy of Rituxirel™ arm with reference arm, whereas the secondary objective is to evaluate safety of Rituxirel™ arm with the reference arm in patients diagnosed with NHL. Results: The first patient was enrolled on April 30, 2012 and the efficacy and safety analysis was performed at 24 weeks. The objective response rate (ORR) was observed to be 87.87% in Rituxirel™ arm. 45.45% patients showed complete response and 42.42% patients showed partial response in Rituxirel™ arm. The ORR was observed to be 86.66% in the reference arm. 33.33% patients showed complete response and 53.33% patients showed partial response in reference arm in the Rituxirel™ arm, the most commonly reported treatment-emergent adverse events (TEAEs) related to blood and lymphatic system disorders were 52.94%, whereas in the reference arm, the reported TEAEs related to blood and lymphatic system disorders were 70%. Conclusion: Based on the results from the efficacy and safety analysis at week 24, Rituxirel™ arm was found to be as effective and safe as the reference arm. Rituxirel™ arm can be a prudent option to the reference arm, in patients undergoing treatment for DLBCL or FL.
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Alekseev, B. Ya, and I. M. Shevchuk. "Evaluation of the efficacy and safety of cabazitaxel in combination with prednisone in patients with metastatic castration-resistant prostate cancer who have previously received docetaxel chemotherapy in daily clinical practice. Results of a Russian multicenter prospective study." Cancer Urology 16, no. 1 (April 23, 2020): 66–77. http://dx.doi.org/10.17650/1726-9776-2020-16-1-66-77.
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Materials and methods. From September 19, 2016 to December 27, 2019, 104 patients received cabazitaxel plus prednisone for a maximum of 10 cycles or disease progression, or unacceptable toxicity, or patient request to stop treatment. Adverse events occurring during treatment, including use of granulocytic colony stimulating factors, were collected. Prostate specific antigen response, objective tumor response (RECIST), progression-free survival and overall survival were analyzed. Treatment period was followed by a follow-up period of 82.0 (36.0–117.0) weeks. Results. 104 patients with histologically proven adenocarcinoma were enrolled and treated. All were Caucasian with a median age of 66 (range 46.0–86.0) years and a median BMI-Score of 26.8 (18.7–43.3) kg/m2. Most patients (57/104, 54.8 %) were ECOG 1. At the time of prostate cancer diagnosis, 63/104 (60.6 %) patients had metastatic disease. The median duration of therapy was 14.5 (0.1–39.0) weeks and the median number of cycles cabazitaxel was 5; 30 (28.8 %) patients received 10 cycles of treatment. Granulocytic colony stimulating factors was received by 52 (50.0 %) patients (prophylactic, n = 31; curative, n = 21). Overall, 102/104 (98.08 %) patients reported at least one treatment emergent adverse event (TEAE), 21/104 (20.19 %) grade ³III TEAEs and 12/104 (11.54 %) serious adverse events. Most TEAEs resolved but 9/104 patients discontinued treatment due to TEAE. Most common TEAEs were related to gastrointestinal system disorders (46/104 (44.23 %) patients, mainly nausea n = 40); blood and lymphatic system disorders (44 (42.31 %) patients, mainly leukopenia n = 22, anemia n = 15, neutropenia n = 11) and general disorders/administration site conditions (22 (21.15 %) patients; mainly asthenia n = 21). Main grade ³III adverse events were related to blood and lymphatic system disorders (11 (10.58 %), including one case of febrile neutropenia), general disorders/administration site conditions (6 (5.77 %), mainly asthenia) and cardiac disorders in 2 (1.92 %) patients. A prostate specific antigen decline of at least 50 % was observed in 23 out of 31 patients with evaluable prostate specific antigen measurements. The objective tumor response was observed in 29 (27.9 %) patients, including 7 (6,7 %) with complete response and 22 (21.2 %) with partial response. Treatment was completed as initially planned in 41/104 (39.4 %) patients, and 61/104 (58.7 %) reached the last follow-up visit. At the last follow-up visit, median overall survival was not reached due to a low number of events. Median progression-free survival at the end of treatment visit was 6.29 (5.1–10.45) months and reached 10.13 (5.55–19.27) months at the last follow-up visit. There was no reported death related to treatment of cabazitaxel during the period of treatment and follow-up period. Conclusion. This prospective, multi-center, national observational, non-interventional register conducted in patients with mCRPC in Russian Federation suggests that cabazitaxel is effective with a manageable safety profile.
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Oliveira, Louise, Eberval Figueiredo, and Carlos Peres. "The Glymphatic System: A Review." Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery 37, no. 03 (July 27, 2018): 190–95. http://dx.doi.org/10.1055/s-0038-1667052.
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AbstractThe brain represents ∼ 2% of the adult body mass; conversely, it is responsible for 20% to 25% of the glucose and 20% of the oxygen consumption, receiving 15% of the cardiac output. This substantial metabolic rate is associated with a significant production of biological debris, which is potentially toxic. Therefore, a complex and efficient clearance system is required to prevent the accumulation of byproducts and ensure optimal function. However, until today, there is little knowledge about this topic. The glymphatic system, also known as perivascular pathway, is a recently described glial-dependent network that is responsible for the clearance of metabolites from the central nervous system (CNS), playing a role equivalent to the one played by the lymphatic vessels present in other organs. Studies have demonstrated that the glymphatic pathway has a paramount role in protein homeostasis, and that the malfunction of this system may be related to the development of neurodegenerative disorders such as Alzheimer disease and normal pressure hydrocephalus. They also showed that body posture, exercise and the state of consciousness influence the glymphatic transport. In this context, the understanding of this clearance system could not only clarify the pathophysiology of several diseases, but also contribute to future therapeutic interventions. In the present article, we will evaluate the glymphatic pathway, focusing on the factors that regulate its flow, as well as on its role in CNS physiology and in disease initiation and progression, including dementia, hydrocephalus, glaucoma and traumatic brain injury. Ultimately, this review also aims to encourage further research on novel therapeutic targets.
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Nagra, Gurjit, Lena Koh, Andrei Zakharov, Dianna Armstrong, and Miles Johnston. "Quantification of cerebrospinal fluid transport across the cribriform plate into lymphatics in rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 291, no. 5 (November 2006): R1383—R1389. http://dx.doi.org/10.1152/ajpregu.00235.2006.
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A major pathway by which cerebrospinal fluid (CSF) is removed from the cranium is transport through the cribriform plate in association with the olfactory nerves. CSF is then absorbed into lymphatics located in the submucosa of the olfactory epithelium (olfactory turbinates). In an attempt to provide a quantitative measure of this transport,125I-human serum albumin (HSA) was injected into the lateral ventricles of adult Fisher 344 rats. The animals were killed at 10, 20, 30, 40, and 60 min after injection, and tissue samples, including blood (from heart puncture), skeletal muscle, spleen, liver, kidney, and tail were excised for radioactive assessment. The remains were frozen. To sample the olfactory turbinates, angled coronal tissue sections anterior to the cribriform plate were prepared from the frozen heads. The average concentration of125I-HSA was higher in the middle olfactory turbinates than in any other tissue with peak concentrations achieved 30 min after injection. At this point, the recoveries of injected tracer (percent injected dose/g tissue) were 9.4% middle turbinates, 1.6% blood, 0.04% skeletal muscle, 0.2% spleen, 0.3% liver, 0.3% kidney, and 0.09% tail. The current belief that arachnoid projections are responsible for CSF drainage fails to explain some important issues related to the pathogenesis of CSF disorders. The rapid movement of the CSF tracer into the olfactory turbinates further supports a role for lymphatics in CSF absorption and provides the basis of a method to investigate the novel concept that diseases associated with the CSF system may involve impaired lymphatic CSF transport.
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Condratovici, Alina Plesea, Alina Mihaela Elisei, Decebal Vasincu, Iulian Dan Cuciureanu, Aurel Nechita, Camelia Ana Grigore, and Catalin Plesea Condratovici. "Biological Chemistry in Intermediate Lipid Metabolism Disorder." Revista de Chimie 70, no. 7 (August 15, 2019): 2647–51. http://dx.doi.org/10.37358/rc.19.7.7397.
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Any pathological process is accompanied by quantitative and qualitative changes in metabolism, which is the main form of life manifestation. Metabolism disorders (it is the permanent exchange of substances between the body and the environment) arise if the activity of the central nervous system is affected; the trophic function of the nervous system directs nutrition and metabolism. In this function, the coordinating role belongs to the central nervous system and is made by means of the endocrine glands. Lipids introduced into the body are digested mainly with the help of the pancreatic and intestinal juice and are resorbed through the walls of the small intestine. Even in the intestinal wall, the re-synthesis of fatty acids and glycerine fat occurs. A certain amount of neutral fat is probably resorbed without being split into fatty acids and glycerine. Fats are mainly resorbed through the lymphatic system, in part (about 30%) by means of the portal vein system; the entire fat emulsion penetrates into the blood and its main mass is deposited in certain fat deposits: the adipose subcutaneous cell tissue, the epiploon and the mesenterium of the abdominal cavity, as well as in the fatty layers of the various organs. In fat deposits, processes of lipid formation from carbohydrates and of transformation of higher fatty acids can occur. Lipids from fat deposits are subject to oxidation, especially at the liver level.
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Abdreshov, S. N., B. М. Sеrik, А. Т. Mamatаeva, Р. S. Utegalieva, and N. I. Zhаparkulоva. "THE IMPACT OF LEAD SALTS ON BIOCHEMICAL PARAMETERS IN THE LYMPH OF ANIMALS." REPORTS 335, no. 1 (February 12, 2021): 83–89. http://dx.doi.org/10.32014/2021.2518-1483.12.
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The article establishes the effect on the biochemical parameters of animal lymphocytes in case of poisoning with lead salts. The impact of lead salts, their spread, the effect of the harmful factors and the strengthening of the ecological situation in the environment determine the urgency of this problem. It is known that heavy metal ions gradually accumulate in the elements of the environment and then pass from the atmosphere to water and the human body. It was found that the effect of heavy metal salts in rats, including lead salts, has a negative effect on the lymphatic and circulatory system compared to the control group of biochemical parameters, which leads to metabolic disorders in the blood and lymph circulation. As a result of the study, the activity of rat enzymes was detected in normal and after poisoning with a toxicant. In acute poisoning, there was an increase in the amount of alkaline phosphatase in the lymphatic system by 40%, as well as an increase in the level of amino-transferase enzymes by 71% and 83%, respectively, and a decrease in the content of total bilirubin and associated bilirubin, all this indicates a violation of liver function, increased cytological processes in the liver and pancreas, decreased protein synthesis and impaired metabolism. When exposed to lead salts on the biochemical parameters of the lymph, the activity of α-amylase was reduced by 22.7%. based on the experiments, it was found that heavy metal salts significantly reduce the level of glucose in the blood, which negatively affects the parenchyma of the liver, kidney and kidney, increasing its consumption in tissues. The results obtained in the course of the study allowed us to form comprehensive data on the effect of lead on lymphatic and circulatory activity, biochemical parameters of the lymph of animal rats and can serve as a scientific basis for finding solutions to this problem.
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Afanasova, N., Zurab Shavladze, Alena Terekhova, and Svetlana Shakhtarina. "POTENTIALITIES OF THE X-RAY DIAGNOSIS OF LYMPH FLOW DISORDERS IN THORACIC ORGANS ASSOCIATED WITH COMPRESSION SYNDROME IN PATIENTS WITH PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA." Problems in oncology 66, no. 1 (January 1, 2020): 90–95. http://dx.doi.org/10.37469/0507-3758-2020-66-1-90-95.
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A comparative analysis of the results of digital radiography (DR) and spiral computed tomography (SCT) of thoracic organs was performed. Data obtained in this work and analysis of research findings on anatomy, physiology of the thoracic lymphatic system helped us understand the mechanism of tumor cell dissemination in this type of lymphoma. Anterograde dissemination of lymphoma cells led to the replacement of lymphoid tissue of the anterior mediastinal lymph nodes by tumor tissue and as a result, their filtration was disturbed. A blockade of lymph flow caused conversion of the anterograde lymph flow to the retrograde one, which provided additional accumulation of tumor cells in the lungs, pleura, epicardium, pericardium, sternum, ribs, thyroid gland, mammary gland and muscles of the anterior thoracic wall.
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Carroll, James, and Bruce Chesebro. "Neuroinflammation, Microglia, and Cell-Association during Prion Disease." Viruses 11, no. 1 (January 15, 2019): 65. http://dx.doi.org/10.3390/v11010065.
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Prion disorders are transmissible diseases caused by a proteinaceous infectious agent that can infect the lymphatic and nervous systems. The clinical features of prion diseases can vary, but common hallmarks in the central nervous system (CNS) are deposition of abnormally folded protease-resistant prion protein (PrPres or PrPSc), astrogliosis, microgliosis, and neurodegeneration. Numerous proinflammatory effectors expressed by astrocytes and microglia are increased in the brain during prion infection, with many of them potentially damaging to neurons when chronically upregulated. Microglia are important first responders to foreign agents and damaged cells in the CNS, but these immune-like cells also serve many essential functions in the healthy CNS. Our current understanding is that microglia are beneficial during prion infection and critical to host defense against prion disease. Studies indicate that reduction of the microglial population accelerates disease and increases PrPSc burden in the CNS. Thus, microglia are unlikely to be a foci of prion propagation in the brain. In contrast, neurons and astrocytes are known to be involved in prion replication and spread. Moreover, certain astrocytes, such as A1 reactive astrocytes, have proven neurotoxic in other neurodegenerative diseases, and thus might also influence the progression of prion-associated neurodegeneration.
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Perrin, R. N. "Chronic fatigue syndrome/myalgic encephalomyelitis: diagnosis from an osteopathic perspective." Russian Osteopathic Journal, no. 1-2 (August 8, 2018): 19–27. http://dx.doi.org/10.32885/2220-0975-2018-1-2-19-27.
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Introduction. To date, there have existed different sets of symptoms of CFS/ME. Scientifi c ideas about the clinical manifestation of this disease continue to appear.Goal of research - to justify osteopathic approach in diagnostics of CFS/ME.Materials and methods. Analysis of approaches to the diagnostics of CFS/ME, osteopathic diagnostics.Results. The author describes the possible pathogenesis of CFS/ME, which may be related to the neurolymphatic changes connected with the alteration of the drainage. All of this leads to dysfunctions of the sympathetic system. Medical history of patients with CFS/ME often contains indications on spinal trauma or congenital developmental disorders of the cranium and vertebral column, which may alter the function of the lymphatic system and lead to the further central neurotoxicity through perivascular spaces. The article presents a protocol of physical signs, typical for patients with CFS/ME, and the results of diagnostics of 94 patients: 52 patients with CFS/ME and 42 non-CFS/ME controls.Conclusion. The research concluded that examining for physical signs is both quick and simple for the practitioner and may be used as an effi cient screening tool for CFS/ME.
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Maddaluno, Luigi, Sue Ellen Verbrugge, Chiara Martinoli, Gianluca Matteoli, Andrea Chiavelli, Yiping Zeng, Elizabeth D. Williams, Maria Rescigno, and Ugo Cavallaro. "The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells." Journal of Experimental Medicine 206, no. 3 (March 9, 2009): 623–35. http://dx.doi.org/10.1084/jem.20081211.
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The adhesion molecule L1, which is extensively characterized in the nervous system, is also expressed in dendritic cells (DCs), but its function there has remained elusive. To address this issue, we ablated L1 expression in DCs of conditional knockout mice. L1-deficient DCs were impaired in adhesion to and transmigration through monolayers of either lymphatic or blood vessel endothelial cells, implicating L1 in transendothelial migration of DCs. In agreement with these findings, L1 was expressed in cutaneous DCs that migrated to draining lymph nodes, and its ablation reduced DC trafficking in vivo. Within the skin, L1 was found in Langerhans cells but not in dermal DCs, and L1 deficiency impaired Langerhans cell migration. Under inflammatory conditions, L1 also became expressed in vascular endothelium and enhanced transmigration of DCs, likely through L1 homophilic interactions. Our results implicate L1 in the regulation of DC trafficking and shed light on novel mechanisms underlying transendothelial migration of DCs. These observations might offer novel therapeutic perspectives for the treatment of certain immunological disorders.
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Zignego, Anna Linda, Carlo Giannini, and Laura Gragnani. "HCV and Lymphoproliferation." Clinical and Developmental Immunology 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/980942.
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Hepatitis C virus (HCV) infection is a serious public health problem because of its worldwide diffusion and sequelae. It is not only a hepatotropic but also a lymphotropic agent and is responsible not only for liver injury—potentially evolving to cirrhosis and hepatocellular carcinoma—but also for a series of sometimes severely disabling extrahepatic diseases and, in particular, B-cell lymphoproliferative disorders. These latter range from benign, but prelymphomatous conditions, like mixed cryoglobulinemia, to frank lymphomas. Analogously withHelicobacter pylorirelated lymphomagenesis, the study of the effects of viral eradication confirmed the etiopathogenetic role of HCV and showed it is an ideal model for better understanding of the molecular mechanisms involved. Concerning these latter, several hypotheses have been proposed over the past two decades which are not mutually exclusive. These hypotheses have variously emphasized the important role played by sustained stimulation of the immune system by HCV, infection of the lymphatic cells, viral proteins, chromosomal aberrations, cytokines, or microRNA molecules. In this paper we describe the main hypotheses that have been proposed with the corresponding principal supporting data.
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Bahri, Shivani. "A Comprehensive Review on Autoimmune Diseases." International Journal for Research in Applied Science and Engineering Technology 9, no. 9 (September 30, 2021): 1477–89. http://dx.doi.org/10.22214/ijraset.2021.38196.
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Abstract: Immunity refers to the inbuilt ability of the organism to resist a particular disease or to be able to protect itself from disease causing microorganisms by preventing its development. Immune system includes WBCs which includes all the neutrophils, lymphocytes including the T-cells, the B-cells & the natural killer cells, all together make up the lymphatic system, antibodies, the spleen, the thymus, the bone marrow; our skin, mucous glands, hair, tears etc. also protect our body. By autoimmunity we understand that it is misallocated response of our immune system when it releases autoantibodies to attack the healthy cells of the body. Scientists have studied a lot about autoimmunity and its disorders. By the end of the 19th century, it was first believed that our immune system has the inability to react against its own body tissue until in 20th century the concept of “horror autotoxicus” was proposed by the German immunologist Paul Ehrlich. The autoimmune disease occurs when the immune system reacts and attacks its own cells in the body as a result of breakdown of immunologic tolerance to auto reactive immune cells. Many times, genetic as well as environmental factors are the key reason for autoimmune diseases. Many kinds of research are going through as to find out the actual cause of autoimmunity; till now no actual or exact cause is known. There are at least 80 types of autoimmune diseases recognized by our scientists; some of the commonly known autoimmune diseases are: type 1 diabetes, systemic lupus erythematosus, scleroderma, thyroiditis, multiple sclerosis, autoimmune vasculitis, rheumatoid arthritis, and many more. With unusual autoimmune diseases, diagnosis may not be done instantly; the patients may suffer years before getting diagnosed properly. Most of the diseases don't have any cure; some even need lifelong treatment to ease the symptoms. The diseases will be discussed in detail in the further sections. Keywords: autoimmunity, immune system, cells, disease, disorder, diabetes, arthritis, lupus, ITP
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Burdea, Liliana, and Roxana L. Aguirre. "A Pediatric Patient With Noonan Syndrome and Late Onset Unilateral Lymphedema." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A694—A695. http://dx.doi.org/10.1210/jendso/bvab048.1415.
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Abstract Introduction: Noonan syndrome is a common autosomal dominant disorder with a prevalence of 1 in 1000-2500 births. The lymphatic disorders in Noonan syndrome are rare and usually bilateral. We present a 14-year-old male with Noonan syndrome and late-onset unilateral lower extremity lymphedema. Case presentation: A 14-year-old male with Noonan syndrome due to a pathogenic mutation in the RIT1 gene (c.265T>C p.Tyro89His) presented to emergency room due to progressive swelling of the right lower extremity. No history of recent trauma or injury. He had a history of small mid-muscular ventricular septal defect (VSD), chylothorax with right-sided pleural effusions during infancy, sensorineural hearing loss with bilateral hearing aids, and undescended testes status post-surgery. He had been on growth hormone (GH) therapy since age 12 years with good adherence and no reported side effects. In the emergency room, initial laboratory evaluation and Doppler ultrasound ruled out deep venous thrombosis. Physical exam was remarkable for edema of the right lower extremity, warm to touch, with erythema, not painful. Due to initial concerns for cellulitis, the patient was treated with antibiotics. Erythema improved but not the edema. Cardiac evaluation including echocardiogram with stable, unchanged VSD was unremarkable. Patient underwent additional workup notable for an albumin level of 4.4g/dl (3.4-5.0), Immunoglobulin (Ig) A 53 mg/dl (66-436), IgG 788 mg/dl (791-1643), IgM 82 mg/dl (43-279) and a stool alpha antitrypsin level of 0.65 mg/g (0.0-0.5) ruling out protein-losing enteropathy (PLE). Growth hormone was held initially and restarted after 2 months due to clinical improvement, but just for one week due to worsening swelling. Lymphoscintigraphy of lower extremities showed an asymmetry between the right and left leg in the transit, suggesting a mild lymphatic abnormality in the right leg. There was a significant improvement in terms of his lymphedema with physical therapy and compressive stocking after 6 months. He has been off growth hormone therapy since then. Discussion: Patients with Noonan syndrome may develop lymphedema and PLE, although findings are usually bilateral. Interestingly our patient has unilateral lymphedema that has been improving with compression stocks and physical therapy. Our patient was on GH therapy for 2 years before he developed lymphedema and although growth hormone causes water retention, we would not expect a selective involvement as in our patient. Based on his history of chylothorax we decided to perform a Lymphoscintigraphy that confirmed an abnormality in the lymphatic system of the right lower extremity. The effect of GH once restarting pointed it was a precipitating factor instead of the cause. Late-onset lymphedema is an uncommon presentation but should be a diagnosis that we have to keep in mind when patients with Noonan syndrome are presenting with edema.
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D’Haens, Geert R. A. M., Neal Slatkin, Robert Israel, and Zeev Heimanson. "P097 FAVORABLE SAFETY PROFILE FOR AMISELIMOD, A SELECTIVE S1P RECEPTOR MODULATOR, IN CROHN’S DISEASE." Inflammatory Bowel Diseases 26, Supplement_1 (January 2020): S1—S2. http://dx.doi.org/10.1093/ibd/zaa010.002.
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Abstract Background Sphingosine 1-phosphate (S1P) receptor modulators are being developed to treat autoimmune-mediated diseases, including ulcerative colitis (UC) and Crohn’s disease (CD). Amiselimod (AMS), a second-generation S1P receptor modulator, was developed to reduce bradycardia associated with other S1P receptor modulators, including fingolimod. Methods This multicenter, randomized, double-blind, parallel group, placebo (PBO)-controlled (DBPC) phase 2a clinical trial in adults with moderate to severe active CD evaluated the safety and efficacy of oral AMS 0.4 mg/d for 14 wks, followed by open-label extension (OLE) of AMS for ≤36 wks. Patients were required to have used corticosteroids, immunosuppressants, or anti-TNF-α agents for CD treatment. The primary efficacy endpoint was a 100-point drop at wk 12 in the Crohn’s Disease Activity Index. Results Of the 78 patients randomized 1:1 to receive AMS (n=40) or PBO (n=38), 78% [n=61] completed the DBPC phase. Of those continuing into the OLE, 26 (AMS/AMS [n=14]; PBO/AMS [n=12]) completed it. AMS 0.4 mg for 12 wks did not have a significant effect on clinical disease activity (CDA) in CD. At least 1 treatment-related adverse event (TRAE) was reported by 31% receiving AMS and 24% receiving PBO; the most frequently reported TREAs for AMS were skin and subcutaneous tissue disorders (10%), infections and infestations, musculoskeletal and connective tissue disorders, nervous system disorders, and cardiac disorders (all 8%). Five serious AEs (SAEs) led to treatment discontinuation (1 in the PBO group; 4 in the AMS group). In the OLE, more PBO/AMS patients (40%) vs AMS/AMS (33%) reported TRAEs; most frequent TRAEs for AMS/AMS were blood and lymphatic system disorders (14%) and investigations (14%). Of 13 SAEs reported by 9 patients, 2 treatment-related SAEs (1 in the PBO/AMS group) led to treatment discontinuation. In the DBPC study, cardiac disorders, all mild, were reported in 3 in the AMS group vs 1 in the PBO group; in the OLE, cardiac disorders were reported by 1 in the AMS group and 1 in the PBO group. There were no clinically significant reports of bradycardia, ventricular tachycardia, or atrioventricular block in the AMS group in either study. In the DBPC study, macular edema (ME) was confirmed in 1 AMS patient (mild/nonserious); none were reported in the OLE. There were no deaths, opportunistic infections, clinically significant negative laboratory or abnormal ECG findings after AMS treatment. Conclusions Oral AMS 0.4 mg was generally well tolerated, with no new safety concerns identified. Other than 1 patient with mild ME, there were no other findings related to the known AMS risk profile. While AMS did not have an effect on CDA in previously treated CD, this favorable safety profile, including no clinically significant reports of bradycardia, is promising for treatment of other autoimmune-mediated diseases, including UC.
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Schalke, Berthold, Sandra Boy, Hans-Stefan Hofmann, Philipp Stroebel, Joerg Marienhagen, Christoph May, Andrea Stuermer, and Alexander Marx. "Neoadjuvant treatment of primary inoperable or local recurrent thymoma with octreotide LAR to improve tumor resectability." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 7105. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.7105.
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7105 Background: The therapeutic outcome for unresectable, locally advanced, malignant thymoma is poor. Most important factor for long-term survival in thymoma patients is complete resection (R0) of the tumor. The study was performed to evaluate the efficacy of octreotide LAR plus prednisone in patients with primary inoperable or local recurrent thymoma to reduce tumor size. Methods: This was an open label, single-arm study in patients with inoperable or local recurrent thymoma. Patients were considered unlikely to achieve R0 resection at enrollment. Octreotide LAR was administered once every 2 weeks in combination with prednisone. Two stages were planned according to Fleming’s one sample multiple testing procedure for phase II clinical trials. The objective of the study was to show that octreotide LAR is effective in this patient population with respect to tumor shrinkage. Response was defined as decrease in tumor volume of at least 20% at month 3 as compared to baseline. Results: 17 thymoma patients at Masaoka stage III were recruited. Octreotide LAR showed a response in 15 of 17 patients (88.24%) at week 12. Two patients had discontinued the study before week 12 due to unsatisfactory therapeutic effect or adverse events. At Week 12, 5 patients (29.41%) operable for radical resection. 10 patients (58.82%) were not operable for radical resection. 16 of 17 patients (94.12%) experienced adverse events (AEs). The most frequent AEs were gastrointestinal disorders (70.59%), infections and infestations (64.71%), and blood/lymphatic system disorders (41.18%). Conclusions: Octreotide LAR was shown to be effective in patients with inoperable thymoma with respect to tumor shrinkage.Octreotide LAR was generally well tolerated. The reported AEs are in accordance with the known safety profile.
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Mendes, Diogo, Graça Rigueiro, Rui S. Silva, Ana Penedones, Carlos Alves, Gabriela Sousa, and Francisco Batel-Marques. "Intensive safety monitoring program of antineoplastic medicines: A pilot study in a Portuguese oncology hospital." Journal of Oncology Pharmacy Practice 26, no. 1 (May 22, 2019): 133–40. http://dx.doi.org/10.1177/1078155219849277.
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Purpose The aim of this study was to test the feasibility and the usefulness of an intensive safety monitoring program to identify adverse drug reactions for medicines under additional monitoring that are used to treat cancer patients within a Portuguese oncology hospital. Methods This pilot intensive safety monitoring program was a three-month prospective, observational study. Patients undergoing treatment with one of the following medicines were included: nivolumab, olaparib, palbociclib, pembrolizumab, pertuzumab, ramucirumab, ribociclib, trastuzumab emtansine, or trifluridine/tipiracil. Potential eligible patients were identified by pharmacists based on prescription data. Clinicians used proper paper-based reporting forms to record adverse drug reactions. Clinical secretariats sent those reports through an electronic platform to the pharmacovigilance department for analysis. Results Seventy-five patients were on treatment with selected medicines. Of those, 33 (44%) experienced adverse drug reactions: 23 (69.7%) cases were serious and 5 (15.2%) unexpected. Considering the number of patients exposed to each medicine and the number of patients experiencing adverse drug reactions, trifluridine/tipiracil (72.7%; 8/11) was associated with the highest rate of toxicity, followed by olaparib (66.7%; 2/3), trastuzumab emtansine (50.0%; 3/6), pertuzumab (47.8%; 11/23), pembrolizumab (45.5%; 5/11), palbociclib (25.0%; 1/4), and nivolumab (18.8%; 3/16). A total of 59 adverse drug reactions were identified (i.e. 1.8 adverse drug reactions/patient), mainly gastrointestinal disorders ( n = 15; 25.4%), and blood and lymphatic system disorders ( n = 14; 23.7%). Conclusion This intensive safety monitoring program was feasible and allowed identifying serious and unexpected adverse drug reactions, adding value to pharmacovigilance and therefore contributing to improve patient safety. Further research is needed to confirm the findings of this pilot study.
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Aagaard, Beverly D. L., Joon K. Song, Joseph M. Eskridge, and Marc R. Mayberg. "Complex right hemisphere developmental venous anomaly associated with multiple facial hemangiomas." Journal of Neurosurgery 90, no. 4 (April 1999): 766–69. http://dx.doi.org/10.3171/jns.1999.90.4.0766.
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✓ Complex developmental venous anomalies (DVAs) represent variations of normal cerebral venous drainage and consist of dilation of the superficial and/or deep venous system. These rare anomalies can occur unilaterally or bilaterally, supratentorially or infratentorially, focally or they can affect the entire hemisphere. Some DVAs are associated with cervicofacial venous malformations or facial lymphatic malformations. Anomalies of this type are generally clinically silent, and cerebral dysfunction is usually absent. Symptoms, when they occur, are most commonly headache or mild seizure disorders. The angiographic findings are striking, with well-formed but enlarged transcerebral medullary and deep and/or superficial cortical veins. Opacification of these venous structures occurs within the same time frame as a normal angiographic venous phase.The authors report the case of a 33-year-old man in whom a large inoperable arteriovenous malformation had been previously diagnosed and who presented with seizures. Repeated magnetic resonance imaging and angiography demonstrated abnormally dilated transcerebral, superficial, and deep venous structures involving the entire right hemisphere with no identifiable nidus. Additionally, multiple bilateral benign facial hemangiomas were present in this patient.It is important to recognize this rare venous appearance as a developmental variant and not mistake it for an arteriovenous malformation or a partially thrombosed vein of Galen malformation. Because these venous anomalies are extreme variants of the normal venous system, hemorrhage rarely, if ever, occurs and the patient can be reassured that no interventional or surgical therapy is necessary or warranted.
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Komelyagin, Dmitry Yu, Svetlana V. Yamatina, Alexey V. Petukhov, Zhanna R. Omarova, Kira A. Blagikh, Elena V. Striga, Galina A. Generalova, et al. "Innovative and high-technology methods of treating children with vascular malformations of the tongue." City Healthcare 2, no. 1 (April 15, 2021): 22–35. http://dx.doi.org/10.47619/2713-2617.zm.2021.v2i1;22-35.
Full textAbstract:
Introduction. Children with various forms of vascular malformations of the tongue are an extremely complex patient
population for a number of reasons: the quality of life of the child is significantly reduced – in addition to cosmetic problems,
occur functional disorders, characterized by impaired breathing, act of swallowing, chewing food, speech, the appearance of pain
syndrome, the child’s social adaptation worsens; the uniqueness of each clinical case, which requires an individual approach to
the treatment of a particular child; frequent combination of malformation (malformation of all types of vessels – arterial, venous, lymphatic); the absence of a clear algorithm for the diagnosis and treatment of this group of patients in the domestic and foreign literature. In this regard, the full rehabilitation of such children requires a search for optimal treatment methods, the purpose of which is to achieve a stable good functional and cosmetic result. Materials and methods. 37 children aged 1 to 17 years with lymphatic, lymphovenous, lymphoarteriovenous and venous malformations of the tongue were treated. The average age of the children was 4.7 years. In addition to general clinical data, the mandatory examination methods were – ultrasonography of pathological tissues of the head and neck, study of the blood coagulation system (thromboelastography, thrombodynamics, coagulogram), Doppler ultrasonography of the head and neck vessels, transcranial Doppler, fibrolaryngoscopy, MRI (magnetic resonance imaging) and CT (computed tomography) of the head and neck with intravenous contrast agent. All children underwent surgical treatment; 6 – puncture-sclerosing method with 3 % solution of aethoxysklerol (with venous malformation of the tongue); 9 – curly resection of the tongue and its subsequent plastic surgery with local tissues (with macroglossia in children with lymphatic, lymphovenous and lymphoarteriovenous malformations of the tongue); 31 – laser treatment (with a superficial form of lymphatic, lymphovenous and lymphoarteriovenous malformations of the tongue). It is worth noting that 9 children out of 31 who underwent laser treatment, the first stage was performed curly resection of the tongue and its subsequent plastic surgery with local tissues. Thus, 46 operations were performed on 37 children. To carry out laser treatment was used a laser apparatus LSP-»IRE-Polyus» (ЛСП-«ИРЭ-Полюс»), which allows working with two wavelengths (0.97 μm and 1.55 μm) in two modes (pulse and pulse-periodic). All operations were performed under general anaesthesia. Results. A diagnostic algorithm has been created, new methods for treating children with various forms of vascular malformations of the tongue have been developed and introduced into practice. A good result was achieved in 37 children (100 %). There were no complications. A patent for invention No. 2676832 was obtained for the method of laser treatment. The maximum observation period is 3.5 years. Conclusions. When managing patients with vascular malformations of the tongue, it is necessary to adhere to a clear diagnostic algorithm. Treatment of patients should take place in a multidisciplinary hospital and be interdisciplinary in nature. Treatment should be started immediately when complaints appear; expectant tactics are not warranted. After the treatment and the achievement of a good clinical result, dynamic monitoring of the patient is necessary.
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Mugosa, Snezana, Zoran Dzamic, Majda Sahman-Zaimovic, and Nevenka Lukovac-Janjic. "Adverse drug reactions associated with sunitinib therapy: Characteristics and risk factors." Vojnosanitetski pregled, no. 00 (2020): 145. http://dx.doi.org/10.2298/vsp201109145m.
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Background/Aim: Kidney tumors account for 2-3% of all tumors. Renal cell carcinoma is the tenth most common malignancy. Sunitinib ise used as the first treatment line in patients with a good and intermediate prognosis. The main goal of this study is to analyze the risk factors, frequency and adverse drug reactions (ADRs) of sunitinib in patients with metastatic renal cell carcinoma. Methods: The retropective study included 170 patients treated in Clinic for Oncology of the Clinical Center of Montenegro, Urology Clinic of the Clinical Center of Serbia and Clinic for Oncology of the Clinical Center Nis. As a data source, we used patient medical histories and/or electronic patient records. ADRs were characterized by using Rawlins and Thompson classification. Each ADRs severity was assessed in accordance with the WHO criteria. Causality was assessed using the Naranjo probability scale. Results: Adverse drug reactions of sunitinib occurred in 152 patients (89,4%). ADRs were 89% type A and 11% type C. Disorders of the blood and lymphatic system, gastrointestinal disorders and disorders of the skin and subcutaneous tissue were the most common manifestations of ADRs of sunitinib. Causality assesment was most commonly classified as certain (60%). Serious ADRs occurred in 4.5% of patients. Most patients recovered without consequences. The most common manifestations of ADRs were: leukopenia, hypothyroidism, thrombocytopenia, diarrhea, stomatitis, asthenia and hypertension. All ADRs were expected. The number of concomitant medications and the duration of therapy were shown to be the most significant risk factors for adverse reactions to sunitinib. Conclusion: Our study shows that the incidence of ADRs of sunitinib in patients with kidney cancer is high. The ADRs were mostly moderate and mild in intensity and occurred as a consequence of the pharmacological action of the drug. It is necessary to conduct continuous education of medical oncologists in the field of the safe use of drugs monitoring, as well as patients on sunitinib therapy, in order to improve their awareness of the ADRs of sunitinib and the risk factors that lead to them, with the aim of reducing their frequency.
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Pismenetskaya, I. U., and T. D. Butters. "Molecular and cellular mechanisms of profile changes of charged blood plasma free oligosaccharides in myeloproliferative disorders." Visnyk of Dnipropetrovsk University. Biology, medicine 7, no. 1 (March 12, 2016): 59–64. http://dx.doi.org/10.15421/021611.
Full textAbstract:
Free oligosaccharides (FOS) are unbound to proteins or lipids structural analogs of their glycans. FOS appear as by-products of endoplasmic reticulum synthesis, cell control folding with endoplastic reticulum-associated degradation and lysosomal/endosomal breakdown of glycoconjugates. They may be either neutral or negatively charged depending on the way of their formation. Charged FOS appear during degradation of glycoconjugates in the lysosomal/endosomal system and are natural substrates for lysosomal sialidase-1. FOS are formed inside the cell but some of them can get into the extracellular space, and then into the blood and urine, where both neutral and charged structures were found. Secretion of charged FOS outside of the cell is most likely to be caused by the lysosomal exocytosis. The activity of neuraminidase-1 is known to be connected with the intensity of the lysosomal exocytosis. In our previous studies, it was found that HPLC-profiles of charged FOS were specifically changed in acute and chronic myeloproliferative blood disorders. The objective of this work was to analyze the molecular and cellular mechanisms of these changes and to test the hypothesis of their association with the activity change of lysosomal neuraminidase-1. Plasma samples of patients with acute and chronic leukaemia – polycytaemia vera, chronic idiopathic myelofibrosis, hypoplastic anaemia, myelodysplastic syndrome with transformation, acute lymphatic and acute myelomonocytic leukaemia – were collected for investigation. Plasma samples of practically healthy volunteers were obtained and used for comparison. After plasma deproteinization and FOS purification the oligosaccharides were labelled with anthranilic acid (2-AA), separated into the neutral and charged fractions with QAE Sephadex (Q25-120) chromatography and analysed using high-performance liquid chromatography (HPLC). Glucose unit values were determined following comparison with a 2-AA-labelled glucose oligomer ladder derived from a partial hydrolysate of dextran as an external standard. The data were collected and processed using Empower software. The charged FOS were digested with the sialidase from Arthrobacter ureafaciens. 2-AA – labelled free oligosaccharides from transferrin were used as an external standard for the structure decoding. In this paper, the changes in neraminidase-1 activity was first demonstrated on natural substrates, free oligosaccharides, in vivo. Chromatographic profiles of charged plasma FOS of patients with acute and chronic hematological malignancies revealed decreasing of neuraminidase-1 activity and increasing of the lysosomal exocytosis. Thus, chromatographic profiles of charged plasma FOS appeared to be a sensitive parameter of the lysosomal/endosomal status in normal or pathological states and to open up new prospects for their applications to the development of anti-cancer drugs designed to block the work of the lysosomal/endosomal system and monitoring of their action.
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Kaguelidou, Florentia, Frédérique Beau-Salinas, Pascal Auriche, and Evelyne Jacqz-Aigrain. "NEONATAL ADVERSE DRUG REACTIONS: ANALYSIS OF PHARMACOVIGILANCE REPORTS AFTER DIRECT DRUG EXPOSURE IN FRANCE." Archives of Disease in Childhood 101, no. 1 (December 14, 2015): e1.22-e1. http://dx.doi.org/10.1136/archdischild-2015-310148.29.
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BackgroundTerm and preterm neonates are at higher risk for serious adverse drug reactions than older children and adults. To date, no study has investigated spontaneous reports of adverse drug reactions (ADRs) following direct drug exposure of neonates.MethodsThis is a retrospective study of all spontaneous reports of ADRs registered in the French Pharmacovigilance Database from 1986 to 2012. All reports concerning individuals from birth to ≤30 days, 1 month or 4 weeks were retrieved. ADRs classified as related to ‘pregnancy’ or ‘breastfeeding’ were discarded. Reports were described with regards to characteristics of the infant, the reported ADR(s) (registered according to the Medical Dictionary for Regulatory Activities [MedDRA]) and the reported suspected medicine(s) (registered according to the Anatomical Therapeutic Chemical [ATC] Classification) Causality assessment was performed using the French Causality assessment method.ResultsA total of 1688 unique reports were analysed. More than half of these reports included at least on serious ADR (n=995; 59%). Median age at ADR occurrence was 9 days and a slight predominance of male neonates was observed (male/female ratio of 1.3). Fourteen percent of neonates presented a medical history of preterm birth, infection or genetic and/or congenital abnormality. Overall, 3127 ADRs were described in these reports. The most commonly reported system organ classes (SOCs) were injury, poisoning and procedural complications (16%), general disorders and administration site conditions (12.5%), blood and lymphatic system disorders (12%), gastrointestinal disorders (8%), investigations (8%) and nervous system disorders (8%). In the majority of ADRs reported (n=2279, 73%), infants fully recovered without sequelae but 4% of neonates deceased as a consequence of the reported ADR. Approximately 1/3 of the reported ADRs fell under 10 categories of ADRs the MedDRA classification and 1 out of 5 ADRs was coded as drug maladministration, medication error, overdose or drug maladministration without clinical consequences. A total of 2238 medicinal products out of the 2797 reported were described as suspect or interacting. Therapeutics classes must commonly incriminated were antiinfectives for systemic use and nervous system drugs. Active substances most frequently related to serious adverse reactions were zidovudine, ibuprofen and nevirapine. A total of 4103 drug-ADR pairs were described in the database; the global intrinsic causality score was ‘doubtful/unlikely’ for 35% of them and the extrinsic causality score was ‘never described before’ for only 6% of these pairs. Among the 10 most frequently encountered drug-ADR pairs, 2 active substances were mainly implicated: zidovudine and phytomedione (Vitamin K).ConclusionsWe have provided a unique overview of ADR notifications after direct drug exposure in the neonates. Reporting of ADRs in neonates is scarce. The majority of ADRs are classified as serious and a subsequent proportion is associated to drug administration errors. The number of commonly incriminated drugs is limited and causality assessment is particularly challenging. There is still a need to increase awareness and education of health professionals on neonatal drug safety and to promote detailed ADR reporting in this paediatric population.
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Berger, J., V. Rahms, H. Uhlemann, K. Waldvogel-Röcker, and S. Hahn. "LYR study: Influence of a web-based application on the systematic chronological and effectiveness of network-guided patient management processes in lymphological care." Phlebologie 45, no. 01 (January 2016): 7–14. http://dx.doi.org/10.12687/phleb2286-1-2016.
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SummaryThe systematic acquisition of data for proving the benefit of standard treatment, demonstrating the efficiency of treatment provided by interprofessional patient management processes and providing valid epidemiological data is inadequate or even nonexistent in the treatment of lymphological disorders. The LYR study firstly uses a webbased documentation tool to examine whether treatment quality is ensured under the conditions provided by an outpatient lymph network that has been guaranteed by a systematic and guideline-compliant treatment analogy. The study evaluated the introduction and handling of a web-based documentation platform for joint case management. LYR also stands synonymously for Lymph Register, and represents a feasibility study with regard to establishing a national lymph register. A phase 1 multicentre interventional study of complex physical decongestion therapy on 61 subjects with different lymphological disorders investigated the immediate and late effects of a prespecified treatment analogy and web-based data acquisition with interdisciplinary data access in six regional lymph networks. Findings on the changes to quality of life and on the effect of the frequency of manual lymphatic drainage and the height of lymphological compression bandages on the results of decongestion were documented and data on prescribing periods and the behaviour of cost bearers were acquired. The study results show that a web-based, structured documentation system can usefully support treatment regimens and simplify mutual access to the patient management process. The epidemiological data acquired during the evaluation of the findings sheet are completely new in Germany and are seen as a feasibility study for a national lymph register that is being prepared. LYR also shows that standard treatment (CPD) has positive effects on circumferences, quality of life, and mobility. It was also shown that a high frequency of manual lymph drainage shortened the decongestion treatment period.
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Voskaridou, Ersi, Stephan Lobitz, Uwe Kordes, Regine Grosse, Valentine Brousse, Malika Benkerrou, Mariane De Montalembert, Jean-Antoine Ribeil, and Frederic Galacteros. "Comparison of the Safety Profile of Sickle Cell Disease Patients Treated with Hydroxycarbamide in Off-Label Versus in-Label Prescriptions in the Escort-HU Non Interventional, Prospective, Observational Open-Label Cohort Study." Blood 128, no. 22 (December 2, 2016): 2497. http://dx.doi.org/10.1182/blood.v128.22.2497.2497.
Full textAbstract:
Abstract ESCORT-HU (European Sickle Cell Disease (SCD) COhoRT - HydroxyUrea) is a multicenter prospective non interventional study implemented in Europe, following the European Medical Agency's request to collect more information focused on long-term safety profile of hydroxycarbamide (HU) in SCD patients treated with HU. Primary endpoint of the study is to determine the frequency of adverse events (AEs) under HU treatment Secondary endpoints include the efficacy of HU in labeled indications (prevention of vaso-occlusive complications and of acute thoracic syndrome), frequency of hospitalizations due to SCD events and frequency of blood transfusions. Data collection on the reason for HU initiation permitted to identify in-label (in the therapeutic indication of the European marketing authorization, group 1, G1) and off-label (other therapeutic indication, group 2, G2) prescriptions of HU. Frequency of AEs (including not related to SCD and infections) was compared between adults and children, both in G1 and G2, with focus on the following subclasses: blood and lymphatic system disorders, fever, gastrointestinal disorders, infection, nervous system disorders, skin and subcutaneous tissue disorders and others. As of 6th June 2016 (cut-off date), a cohort of 1047 sickle cell patients have been enrolled in 3 European countries (Greece, 11.4%, Germany, 13.4%, and France, 75.2%). Of the 1047 patients, 845 (80.7%) have an in-label prescription (478 adults and 367 children), 170 (16.2%) an off-label prescription (61 adults and 109 children), and 32 reported unknown or no indication (Table 1a). As usually observed in any disease, the off-label use is more frequent in children compared to adults (p=0.01). Main reasons for off-label prescription were anemia (31%) (n=9 in adults and n=44 in children), abnormal Transcranial Doppler (TCD) values/cerebral vasculopathy (15%) (n=2 in adults and n=24 in children) and sickle cell organopathy including renal impairment (15%) (n=14 in adults and n=12 in children) (Table 1b). These three indications follow recommendations issued by European clinicians and are in accordance with the last version of US guidelines (JAMA 2014). Mean HU daily doses at initiation were respectively 18 mg/kg (G1) and 17.3 mg/kg (G2) in children, and 16.2 mg/kg (G1) and 13.5 mg/kg (G2) in adults. Not SCD-related AEs were respectively reported in 25% and 27.6% of patients in G1 and G2 groups (Table 2a). Focusing on the number of not-SCD related AE reported in each group, 355 AE have been reported in 211 patients in G1 and 73 AE have been reported in 47 patients in G2. Within G1 group, more AEs were reported in adults (30.8%) vs. children (17.4%) (p < 0.01) (Table 2b) but not in G2 group (NS) (Table 2c). When compared by AE type in G1, significant differences appeared between children and adults for the following AE subclasses (p < 0.01): infections more frequent in children as usually observed, renal & urinary disorders, immune system disorders more common in adults. Regarding neoplasms benign, immune system disorders, no malignancy has been reported, but mainly cysts (1 ovary, 2 breast), 1 renal tumor and 1 cutaneous lesion (histological types not provided), 1 other (location not reported) (Table 3). All AEs were more frequent in adults except infections. In conclusion, the current ESCORT-HU data confirm the more frequent off-label use of HU in children, a similar frequency of patients reporting not SCD-related AE between the in-label and off-label groups despite a higher number of AE reported in the in-label group, and a significant difference between children and adults in frequency of AEs in the in-label group. Disclosures De Montalembert: Addmedica: Research Funding; Novartis: Research Funding, Speakers Bureau. Ribeil:Bluebirdbio: Consultancy; Addmedica: Research Funding.
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De Montalembert, Mariane, Frédéric Galacteros, Jean Antoine Ribeil, Uwe Kordes, Jean Benoit Arlet, M. Dimopoulou, V. Komninaka, et al. "Implementation of a European Cohort to Follow Sickle Cell Children and Adults Treated with Hydroxycarbamide." Blood 124, no. 21 (December 6, 2014): 564. http://dx.doi.org/10.1182/blood.v124.21.564.564.
Full textAbstract:
Abstract Hydroxycarbamide (HU) is a myelosuppressive drug marketed since 1968 for the treatment of hematological cancer, and authorized since 2007 in Europe as orphan medicinal product for the prevention of recurrent vaso-occlusive crises including acute chest syndrome in adults and children older than 2 years with sickle cell disease (SCD). ESCORT-HU (European Sickle Cell Disease Cohort – Hydroxyurea) is a multicenter prospective non interventional study implemented in Europe to collect more information about the safety profile of HU and morbi-mortality in SCD patients treated with HU. The study responds to EMA (European Medicines Agency) request and has been approved by the Ethical of Necker Enfants Malades Hospital (Paris, France).The ongoing study involves the largest number so far of patients with SCD treated with HU. Primary endpoints of ESCORT HU are to determine frequency of adverse events, and possible consequent changes of HU treatment. Secondary endpoints are to evaluate morbi-mortality of the disease although in the absence of control group. From June 2008 to June 2014, 483 patients (255 females; 228 males) were enrolled from 3 European countries, Greece (24%), Germany (19%), and France (56%). 67% patients were adults, median aged 37.35 yrs (17-83.5) and 33% were children, median aged 11.06 yrs (2.6-16.9). genotypes were HbS/HbS in 71.4% cases, and compound heterozygotous HbS/β-thalassemia in 22.8 % (Table 1). 137 (28.4%) patients experienced 421 events (Table 2). 132 (32.2%) of these events may be attributed to HU. The safety profile is roughly similar in children and adults. As expected the most frequent side effects were firstly blood disorders (n=86 events, 42.4%) such as neutropenia or thrombocytopenia. In all cases, these cytopenias were rapidly resolved with the transitory stop of HU. 71 events related to skin and subcutaneous tissue disorders were observed, mostly cutaneous dryness, skin reactions, alopecia and nails or skin pigmentation; 4 patients had a leg ulcer (34.8%). Most of these events are ongoing or stabilized despit the decrease of HU. No secondary cancer has been reported until now. Even if HU is an old drug with a relatively well-known safety profile, some uncertainties remain in terms of long-term safety as well as tolerance in the youngest people. The main interest of ESCORT HU is to offer the possibility of safety surveillance of hydroxycarbamide in European sickle cell patients. Table 1 Demographic data Adults Children < 17 years old Total Number of patients 322 (67%) 161 (33%) 483 Females/Males 183/139 72/89 255/228 Median age (yrs) (range) 37.35 (17-83.5) 11.06 (2.6-16.9) 28.58 Genotype SS 206 (64%) 139 (86.3%) 345 (71.4%) SC 1 (0.3%) 3 (1.86%) 4 (0.8%) Sβ0 51 (15.8%) 11 (6.8%) 62 (12.8%) Sβ+ 46 (14.2%) 2 (1.2%) 48 (9.9%) Other 18 (5.5%) 6 (3.7%) 24 (4.9%) Treatment with HU before enrollment in ESCORT HU No of pts 232 83 315 (65%) Median duration (range) of HU treatment before ESCORT HU 8.2 yrs (0.5 ans-24 yrs) 3. 1 yrs ( 71 days – 8.9 yrs) 6.85 (71 days-24 years)] HU ESCORT Daily mean dose (mg/kg/d) 16.11 ± 4.79 19.63 ± 4.69 17.32 ± 4.94 Abstract 564. Table 2 The most frequent events of hydroxycarbamide in the two populations of SCD patients ADULTS CHILDREN No ofGerman(%) No of adults No ofEpisodes(%) No of children Total(% /411) Events Related to HU treatment (Siklos®)(%**) Blood and lymphatic system disorders (%) 32 (17.7) 22 54 (31.03) 28 86 (20.9) 56 (65.1) Skin and subcutaneous tissue disorders (%) 42 (23.2) 28 29 (16.7) 19 71 (17.3) 46 (64.8) Nervous system disorders Headache (24), Dizziness/vertigo (14), 32 (17.7) 23 12(6.9) 10 44 (10.7) 11 (25) Gastrointestinal disorders Nausea (14), diarrhea (8), other (14) 20 (11) 17 23 (13.2) 16 43 (10.4) 7 (16.3) Metabolic and nutrition disorders: vit D deficiency (17), weight gain (5) 13 (7) 11 18 (18.3) 18 36 (8.75) 4 (11.1) Fever 11 (6) 10 12(6.9) 7 23 (5.6) 1 (4.3) Cardiac disorders (hypertension, bradycardia, chest pain, cardiomegaly) 4 4 2 2 6 1 (16.6) General disorders : fatigue 5 5 0 0 5 0 Hepatobiliary disorders 2 2 0 0 2 0 Neoplasms benign, malignant and unspecified (incl. cysts and polyps) Harmatoma, benign vulvar sebaceous cyst 2 2 0 0 2 0 Renal & urinary disorders 2 2 0 0 2 0 Reproductive system and breast disorders 3 3 0 0 3 0 Other 13 13 21 14 34 6 (17.1%) 181 80 /181(24.8%) 174 57 / 174(35.4%) 411 132/411 (32.2%) ** compared to the total number of “system organ class” events Disclosures No relevant conflicts of interest to declare.
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Almonacid, I., P. Zuleta, C. Neri, A. Zannin, M. Garzón, J. Dorado, F. Medina, and L. G. Celis. "CYSTIC HYGROMA AND THE IMPORTANCE OF THE PRENATAL DIAGNOSIS: ABOUT A CASE." Journal of Basic and Applied Genetics 31, Issue 2 (December 2020): 39–44. http://dx.doi.org/10.35407/bag.2020.31.02.04.
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The cystic hygroma is the malformation of the lymphatic system that is most frequently observed in the prenatal period and is located mainly in the neck and/or the nape of the neck. Its detection rate has increased since the implementation of fetal nuchal translucency (NT) in the first trimester of pregnancy and its presence has been associated with congenital abnormalities, aneuploidies, pregnancy loss, and developmental disorders. The aim of this case is to highlight the importance of antenatal diagnosis of cystic hygroma in order to perform early intervention and avoid fetal death. It is received, for anatomopathological study, a fetus of undetermined sex product of the first pregnancy of a 19 year-old mother without previous prenatal controls, with the presence of a large cystic mass that extends from the face to the neck. The histological study confirms the diagnosis of cystic hygroma. As there was no karyotype analysis, it was not possible to establish the preexistence of any genetic abnormality. Also known as cystic lymphangioma, is a benign vascular tumor whose antenatal diagnosis by ultrasonography is essential in the evolution and prognosis of the disease. Unfortunately in our case, the lack of prenatal controls and the absence of ultrasonographic studies that would allow knowing the characteristics of this lymphangioma, could significantly impact in the fatal outcome. Key words: lymphangioma; prenatal diagnosis; fetal nuchal translucency.
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Czarnecki, A. "Gemcitabine and radiotherapy: Analysis of safe use." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 18146. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.18146.
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18146 Background: Radiation in combination with chemotherapy offers a significant survival advantage. Preclinical and clinical data indicate that gemcitabine (GEM) is a potent radiosensitizing agent in numerous cancer types used subsequently with radiation given in different doses and techniques. We compared safety/toxic effects of GEM with GEM plus radiation. Methods: Lilly Safety Database was searched for all reports where patients received radiation before, during and after GEM therapy. The string search for ‘radio’, ‘radia’ and a search for MedDRA terms covering possible radiation recall and typical recall phenomena were conducted. Cases were reviewed by a physician and allocated to one of the categories: ‘concurrent’ (radiation and GEM was given at the same time or 7 days apart), and ‘non-concurrent’ (treatment was given more than 7 days apart). Results: In one third of cases who received concurrent treatment the toxicity reported was higher in 3 System Organ Classes (SOC): ‘Injury’, ‘Gastrointestinal disorders’ (GI), and ‘Respiratory’ in comparison to non radiation treated patients: 4.1%, 16%, 14.8% versus 1.4%, 11.2% and 10.5% respectively but toxicity was lower for ‘Blood and lymphatic disorders’ and ‘General disorders’. In cases with ‘non-concurrent’ treatment the results were similar to ‘concurrent’ treatment for the Injury, Respiratory and Blood SOCs but GI toxicity was only 60% of the one seen in non radiation treated patients. In patients with reported radiation recall the most frequent were skin reactions, pneumonitis and myositis. Radiation injury mainly affected targeted tissue organs exposed to direct radiation e.g eosophagitis and pneumonitis for chest irradiation, GI effects for abdominal irradiation. In Non-concurrent administration no correlation between GEM dose and toxicity could be established. In Concurrent cases, treatment dose and technique of radiation, target tissue and volume were factors together with dose and frequency of GEM administration. Conclusions: Review of adverse drug reactions for GEM and radiation treatment reported from estimated GEM exposure of nearly 1.1 million patients suggests that any increase in GEM toxicity in non- concurrent combination regimen other than radiation recall is due to typical radiation toxicity and mainly affects directly irradiated tissues. No significant financial relationships to disclose.
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Dynnyk, O. B. "Microcirculation as a goal of correction in macroangiopathy (atherogenesis)." Infusion & Chemotherapy, no. 3.2 (December 15, 2020): 80–81. http://dx.doi.org/10.32902/2663-0338-2020-3.2-80-81.
Full textAbstract:
Background. The microcirculatory system (MCS) is a network of blood vessels that includes arterioles, capillaries, venules, and terminal lymphatic vessels. Microcirculation is characterized by the constant variability. Factors of atherogenesis development due to MCS dysfunction include shear stress, hyperglycemia, dyslipidemia, systemic and local inflammation, hypoxia and endothelial dysfunction mediated by oxidative stress. Laser Doppler flowmetry (LDF) is used to study microcirculation in the clinical settings. The advantages of LDF include simplicity, accessibility and non-invasiveness.
Objective. To describe the features of microcirculation disorders and their elimination.
Materials and methods. Analysis of literature data on this topic; own study. The study involved 98 patients (59 females; 39 males) with a mean age of 52.0 years. The first group consisted of patients with coronary heart disease (CHD) and chronic heart failure of I-IIA grades, the second – of relatively healthy individuals. All patients underwent LDF, ultrasound examination of the carotid arteries, and determination of anthropometric parameters.
Results and discussion. MCS dysfunction is not only a risk factor for atherogenesis, but also a trigger for its acute complications (myocardial infarction, stroke, sudden death). Nitric oxide (NO) deficiency plays an important role in this. A potential target of therapeutic influence in the treatment of coronary heart disease is not only macrovascular system, but also vasa vasorum. The condition of the latter determines the course of atherosclerosis. According to the results of our own study, patients with CHD demonstrated a muscle mass decrease, an increase in waist and hip circumference, and in body mass index. In addition, the groups differed in thickness of the intima-media complex of both common carotid arteries (right common carotid artery: CHD group – 0.79±0.18 mm; group of relatively healthy individuals – 0.69±0.13 mm, p<0,05; left common carotid artery: CHD group – 0.81±0.19 mm, group of relatively healthy individuals – 0.70±0.14 mm, p<0,05). When assessing the indicators of wavelet analysis of LDF, a significant decrease in the rate of microcirculation and capillary blood flow reserve is revealed in the CHD group, as well as an increase in peripheral vascular resistance. According to previous own studies, sorbitol (Reosorbilact, “Yuria-Pharm”) and pentoxifylline (Latren, “Yuria-Pharm”) can be used to correct microcirculation disorders. The use of these drugs leads to vasodilation of precapillary sphincters and improvement of regional microperfusion.
Conclusions. 1. Disorders of MCS are the pathogenetic factors of the atherogenesis. 2. Laser Doppler flowmetry is used to study microcirculation in the clinical settings. 3. In patients with CHD there is an increase in neuro- and myotonus of the MCS, which is associated with the impaired release of nitric oxide. 4. Changes in microcirculation contribute to the development of atherosclerosis, which should be taken into account when choosing treatment for such patients. 5. Sorbitol (Reosorbilact) and pentoxifylline (Latren) can be used to correct microcirculation disorders.
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Sente, Marko, and Ruza Sente. "Annual report of the Municipal and Eye Hospital in Subotica for 1889." Medical review 55, no. 5-6 (2002): 253–58. http://dx.doi.org/10.2298/mpns0206253s.
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Introduction The paper is the translation of the report of the Head physician of the Municipal Hospital in Subotica for 1889. It shows the number of patients, the number of checkups, the number of outpatients and inpatients, distribution by sex, age, place of residence, the frequency of patients by months and groups of diseases, the average length of treatment the number of cured, unsuccessfully treated and deceased patients, the most significant surgeries, the number of doctors employed and a detailed survey of groups of diseases. Annual report From January 1, to December 31, 1889 6.123 patients were treated, 5.141 outpatients and 982 inpatients; 24.644 visits, 69 patients on average, 2.884 men and 2.257 women; 662 under 1 year of age; 828 aged 1 to 5; 1.655 aged 5 to 20; 1.854 aged 20 to 80; 142 patients over 80 years of age. 4.260 patients were from Subotica and 881 from other parts of the country. 19.436 patient days were required, 19 3/4 on average. 747 patients were cured, condition improved in 132, 60 were unsuccessfully treated and 43 patients died. Cerebral and spinal cord diseases occurred in 73 outpatients and 38 patients (the same distribution outpatients + inpatients goes for all diseases, respectively); nervous system diseases 82+18; ear diseases 139+2; eye diseases 1706+220; nose diseases 12+0; respiratory tract diseases 478+95; circulatory system diseases 35+13; lymphatic system diseases 51+5; mouth and throat lumen diseases 207+9; coronary diseases and diseases of intestinal mucosa 711+18 genitourinary tract diseases 252+66; skin diseases 440+107; muscle, gland and tissue diseases 104+23; joint diseases 75+16; bone diseases 56+20; acute infectious diseases 344+43; chronic infectious disease 143+137; general nutritional disorders 222+43; poisonings 3+2; childbirths 8+6.
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Jiramongkol, Yannasittha, and Eric W. F. Lam. "FOXO transcription factor family in cancer and metastasis." Cancer and Metastasis Reviews 39, no. 3 (May 5, 2020): 681–709. http://dx.doi.org/10.1007/s10555-020-09883-w.
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Abstract Forkhead box O (FOXO) transcription factors regulate diverse biological processes, affecting development, metabolism, stem cell maintenance and longevity. They have also been increasingly recognised as tumour suppressors through their ability to regulate genes essential for cell proliferation, cell death, senescence, angiogenesis, cell migration and metastasis. Mechanistically, FOXO proteins serve as key connection points to allow diverse proliferative, nutrient and stress signals to converge and integrate with distinct gene networks to control cell fate, metabolism and cancer development. In consequence, deregulation of FOXO expression and function can promote genetic disorders, metabolic diseases, deregulated ageing and cancer. Metastasis is the process by which cancer cells spread from the primary tumour often via the bloodstream or the lymphatic system and is the major cause of cancer death. The regulation and deregulation of FOXO transcription factors occur predominantly at the post-transcriptional and post-translational levels mediated by regulatory non-coding RNAs, their interactions with other protein partners and co-factors and a combination of post-translational modifications (PTMs), including phosphorylation, acetylation, methylation and ubiquitination. This review discusses the role and regulation of FOXO proteins in tumour initiation and progression, with a particular emphasis on cancer metastasis. An understanding of how signalling networks integrate with the FOXO transcription factors to modulate their developmental, metabolic and tumour-suppressive functions in normal tissues and in cancer will offer a new perspective on tumorigenesis and metastasis, and open up therapeutic opportunities for malignant diseases.