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Sample records for chronic graft-versus-host disease

  1. Ibrutinib treatment ameliorates murine chronic graft-versus-host disease

    OpenAIRE

    Dubovsky, Jason A.; Flynn, Ryan; Du, Jing; Harrington, Bonnie K.; Zhong, Yiming; Kaffenberger, Benjamin; Yang, Carrie; Towns, William H; Lehman, Amy; Johnson, Amy J.; Muthusamy, Natarajan; Devine, Steven M.; Jaglowski, Samantha; Serody, Jonathan S.; Murphy, William J.

    2014-01-01

    Chronic graft-versus-host disease (cGVHD) is a life-threatening impediment to allogeneic hematopoietic stem cell transplantation, and current therapies do not completely prevent and/or treat cGVHD. CD4+ T cells and B cells mediate cGVHD; therefore, targeting these populations may inhibit cGVHD pathogenesis. Ibrutinib is an FDA-approved irreversible inhibitor of Bruton’s tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissi...

  2. Chronic graft versus host disease and nephrotic syndrome

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    Samia Barbouch

    2014-01-01

    Full Text Available Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD. We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT. Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed mem-branous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome.

  3. Chronic graft versus host disease and nephrotic syndrome.

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    Barbouch, Samia; Gaied, Hanene; Abdelghani, Khaoula Ben; Goucha, Rim; Lakhal, Amel; Torjemen, Lamia; Hamida, Fethi Ben; Abderrahim, Ezzedine; Maiz, Hedi Ben; Adel, Khedher

    2014-09-01

    Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD). We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT). Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed membranous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome. PMID:25193909

  4. Azacytidine mitigates experimental sclerodermic chronic graft-versus-host disease

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    Fransolet, Gilles; Ehx, Grégory; Somja, Joan; Delens, Loïc; Hannon, Muriel; Muller, Joséphine; Dubois, Sophie; Drion, Pierre; Caers, Jo; Humblet-Baron, Stéphanie; Delvenne, Philippe; Beguin, Yves; Conteduca, Giuseppina; Baron, Frédéric

    2016-01-01

    Background Previous studies have demonstrated that regulatory T cells (Tregs) play a protective role in the pathogenesis of chronic graft-versus-host disease (cGVHD). Tregs constitutively express the gene of the transcription factor Foxp3 whose CNS2 region is heavily methylated in conventional CD4+ T cells (CD4+Tconvs) but demethylated in Tregs. Methods Here, we assessed the impact of azacytidine (AZA) on cGVHD in a well-established murine model of sclerodermic cGVHD (B10.D2 (H-2d) → BALB/cJ ...

  5. Homecare-based motor rehabilitation in musculoskeletal chronic graft versus host disease

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    A Tendas

    2011-01-01

    Full Text Available Chronic graft versus host disease (cGVHD is a frequent complication of allogeneic stem cell transplantation. Extensive musculoskeletal and skin involvement may induce severe functional impairment, disability and quality of life deterioration. Physical rehabilitation is recommended as ancillary therapy in these forms, but experiences are sparse. A 39-year-old man affected by musculoskeletal and skin chronic graft versus host disease (cGVHD was treated with a homecare-based motor rehabilitation program during palliation for disease progression. Significant functional improvement was obtained. Motor rehabilitation should be strongly considered for patients with musculoskeletal cGVHD, both in the palliative and in the curative phase of disease.

  6. Early and late oral features of chronic graft-versus-host disease

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    Alessandra Oliveira Ferrari Gomes

    2014-01-01

    Full Text Available Background: Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. Objective: The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. Methods: This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year. Results: Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72% in the group with less than one year after transplantation, and 34 (77.27% in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. Conclusion: Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation.

  7. Extracorporeal photopheresis for chronic graft-versus-host disease: a systematic review and meta-analysis

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    Malik, Mohsin Ilyas; Litzow, Mark; Hogan, William; Patnaik, Mrinal; Murad, Mohammad Hassan; Prokop, Larry J.; Winters, Jeffrey L.; Hashmi, Shahrukh

    2014-01-01

    Background The safety of extracorporeal photopheresis (ECP) in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) has been explored in multiple studies but reported response rates (RR) vary significantly across studies. Methods We conducted a meta-analysis to assess the efficacy of ECP for SR-cGVHD. A search of electronic databases for studies published between 1984 and 2012 was conducted. End points included RR: complete response (CR), overall response rates (ORR), and organ-spe...

  8. Rapamycin Prevents Experimental Sclerodermatous Chronic Graft-versus-Host Disease in mice

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    Belle, Ludovic; Binsfeld, Marilène; Dubois, Sophie; Hannon, Muriel; Caers, Jo; Briquet, Alexandra; MENTEN, Catherine; Beguin, Yves; Humblet-Baron, S; Baron, Frédéric

    2012-01-01

    Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that mortality is relatively low, making difficult to study the impact of potentially therapeutic compounds. Aims: To develop a more severe model of cGVHD and to assess the impact of Rapamycin administration in that model. Results: Lethally irradiated Balb/C mice were injected with 10x106 bon...

  9. Late Onset and Protracted Course of Steroid Refractory Chronic Graft-versus-Host Disease

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    Gunes, Gursel; Demiroglu, Haluk; Goker, Hakan; Malkan, Umit Yavuz; Eliacik, Eylem; Yayar, Okan; Buyukasik, Yahya

    2015-01-01

    Chronic graft-versus-host disease (cGVHD) is one of the most important causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (aHSCT). Occurring in 30% to 70% of patients, cGVHD has a median time to onset of 4 to 6 months and most cases present within 2 years after aHSCT. Here, we present a patient transplanted at the age of 55 who developed refractory cutaneous cGVHD more than 5.5 years after aHSCT. PMID:26613052

  10. Bilateral herpes simplex keratitis in a patient with chronic graft-versus-host disease

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    Takahiko Hayashi

    2008-06-01

    Full Text Available Takahiko Hayashi1, Misaki Ishioka2, Norihiko Ito1, Yoko Kato1, Hisashi Nakagawa3, Hiroshi Hatano4, Nobuhisa Mizuki11Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan; 2Ryogoku Eye Clinic, Tokyo, Japan; 3Tokushima Eye Clinic, Higashimurayama-shi, Tokyo, Japan; 4Lumine Hatano Eye Clinic, Fujisawa, Fujisawa-shi, Kanagawa, JapanPurpose: To describe a case of bilateral herpes simplex keratitis accompanying chronic graft-versus-host disease (GVHD.Design: Observational case report.Case report: An 11-year-old boy with myelocytic leukemia underwent allogeneic bone marrow transplantation. He developed symptoms of the skin, eyes, and mouth, and lip biopsy indicated chronic GVHD. Persistent keratitis with corneal filaments and neovascularization was noted in both eyes. Sodium hyaluronate, autoserum, and 0.1% fluorometholone eyedrops were instilled for approximately 2 years to treat this keratitis, and there were no other ocular changes. Bilateral herpes simplex keratitis developed with geographic ulcers after topical betamethasone therapy, but responded to acyclovir ointment.Conclusions: Herpes keratitis should be considered in the differential diagnosis of bilateral keratitis in patients with reduced immunocompetence. During the course of chronic GVHD, corneal herpes may occur, so ocular treatment with topical corticosteroids should be managed by an ophthalmologist to monitor sight-threatening conditions such as corneal herpes.Keywords: chronic graft-versus-host disease, bone marrow transplant, corneal herpes, bilateral herpes simplex keratitis, dry eyes

  11. ORAL CHRONIC GRAFT VERSUS HOST DISEASE IN AN IMMUNOCOMPETENT PATIENT: A CASE REPORT

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    Redwin Dhas Manchi

    2014-06-01

    Full Text Available Graft-versus-host disease (GVHD is a complication which occurs in an individual who has received allogenic transplant. This was first noticed in individuals who had undergone bone marrow transplantation. Since then it has been described in solid organ transplantation and even transfusion of blood and blood products. Transfusion-associated GVHD (TA-GVHD is acute or chronic in nature. Acute TA-GVHD is rare and usually runs a fulminant and fatal course. In its chronic form, oral cavity is frequently affected with wide variety of signs and symptoms resulting in significant short and long-term complications ranging from mucosal sensitivity and limited oral in take to secondary malignancy and early death. Herewith we report a case of oral cGVHD in an immuno competent patient who underwent transfusion of platelets from an unrelated donor

  12. Health related quality of life among patients with chronic graft-versus-host disease in China

    Institute of Scientific and Technical Information of China (English)

    MO Xiao-dong; XU Lan-ping; LIU Dai-hong; CHEN Yu-hong; ZHANG Xiao-hui; CHEN Huan; HAN Wei

    2013-01-01

    Background Chronic graft-versus-host disease (GVHD),the commonest long-term complication after allogeneic hematopoietic stem cell transplantation (HSCT),has a negative impact on patients' health related quality of life (HRQoL).This study was designed to investigate the HRQoL in patients with chronic GVHD in China.Methods Two hundred and sixty-four patients with chronic GVHD who were >24 months post-HSCT and had been in continuous complete remission since HSCT were enrolled in this retrospective study.HRQoL was evaluated using an SF-36 questionnaire.Multivariate analysis was used to identify the factors that affect HRQoL in patients with chronic GVHD.Results HRQoL in patients categorized as having mild and moderate chronic GVHD was significantly better than in those in the severe category.In the moderate chronic GVHD category,markedly poorer HRQoL was observed in patients with both multiple organ involvement and more severe organ impairment than in those without these factors.According to multivariate analysis,chronic GVHD severity had the greatest significant negative impact on patients' HRQoL; whereas being female was associated with a negative impact on psychological health.Conclusion Chronic GVHD severity strongly correlates with negative impacts on patients' HRQoL.

  13. Emerging technologies for oral diagnostics: lessons from chronic graft-versus-host disease

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    Mays, Jacqueline W.; Ambatipudi, Kiran S.; Bassim, Carol W.; Melvin, James E.

    2013-05-01

    Saliva is a protein-rich oral fluid that contains information about systemic and oral-specific disease pathogenesis and diagnosis. Technologies are emerging to improve detection of protein components of human saliva for use not only in biomarker discovery, but also for the illumination of pathways involved in oral disease. These include the optimization of liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis of saliva in health and disease. Downstream of saliva component identification and validation comes the complex task of connecting salivary proteomic data to biological function, disease state, and other clinical patient information in a meaningful way. Augmentation of database information with biological expertise is crucial for effective analysis of potential biomarkers and disease pathways in order to improve diagnosis and identify putative therapeutic targets. This presentation will use LC-MS/MS analysis of saliva from chronic Graft-versus-Host disease (cGVHD) patients to illustrate these principles, and includes a discussion of the complex clinical and diagnostic issues related to proteomics and biomarker research in cGVHD.

  14. IL-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-versus-Host Disease

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    Renata Gonçalves Resende

    2014-01-01

    Full Text Available Although interleukin-17 (IL-17 is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4+ T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD.

  15. IL-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-versus-Host Disease

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    Resende, Renata Gonçalves; Correia-Silva, Jeane de Fátima; Silva, Tarcília Aparecida; Salomão, Ulisses Eliezer; Marques-Silva, Luciano; Vieira, Érica Leandro Marciano; Dutra, Walderez Ornelas; Gomez, Ricardo Santiago

    2014-01-01

    Although interleukin-17 (IL-17) is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD) was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4+ T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD. PMID:25136146

  16. Cutaneous graft-versus-host disease after hematopoietic stem cell transplant - a review*

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    Villarreal, Cesar Daniel Villarreal; Alanis, Julio Cesar Salas; Pérez, Jose Carlos Jaime; Candiani, Jorge Ocampo

    2016-01-01

    Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplants (allo-HSCT) associated with significant morbidity and mortality. The earliest and most common manifestation is cutaneous graft-versus-host disease. This review focuses on the pathophysiology, clinical features, prevention and treatment of cutaneous graft-versus-host disease. We discuss various insights into the disease's mechanisms and the different treatments for acute and chronic skin graft-versus-host disease. PMID:27438202

  17. Liver transplantation for chronic graft-versus-host disease: case report with 10-year follow-up.

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    Orlando, Giuseppe; Ferrant, Augustin; Schots, Rik; Goffette, Pierre; Mathijs, Jules; Lemaire, Julien; Danse, Etienne; Talpe, Stéphanie; Latinne, Dominique; Lerut, Jan

    2005-01-01

    Graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation (BMT). Chronic GVHD (cGVHD) may lead to irreversible liver failure. We report a case of successful liver transplantation (LT) for end-stage liver failure because of cGVHD that had developed 22 months after BMT in a 24-year-old male. Re-transplantation was necessary 6 months later because of intrahepatic ischaemic type biliary tract lesions. He is now in excellent condition 10 years after the first transplant. This experience and the review of literature indicate that LT can cure GVHD-related chronic liver failure. Recurrent GVHD in the allograft has not yet been reported. PMID:15612994

  18. Glomerular diseases associated with chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation: case reports.

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    Chanswangphuwana, C; Townamchai, N; Intragumtornchai, T; Bunworasate, U

    2014-12-01

    Chronic graft-versus-host disease (cGVHD) is the major complication following allogeneic stem cell transplantation (allo-SCT). Nephrotic syndrome (NS) and other types of glomerulonephritis have been proposed to be the very rare forms of renal cGVHD. From 1991 to 2011, 253 patients underwent allo-SCT at our center. We report here 4 cases (1.6%) presenting with varieties of glomerular manifestations associated with cGVHD. The first case was typical NS. The renal pathology showed membranous nephropathy (MN). The second case was also MN, but this patient also had the pathology of focal segmental glomerulosclrosis (FSGS) and acute tubular necrosis (ATN). The third case showed lupus nephritis-like glomerular lesions with a high anti-nuclear antibody (ANA) titer. The fourth case presented with rapidly progressive glomerulonephritis (RPGN)-like symptoms. The kidney histology in this case was not available. The patient responded well to immunosuppressive therapy, but NS later recurred. Therefore, overt glomerular diseases after allo-SCT in Thai patients are not very rare. Monitoring urinalysis during withdrawal of immunosuppressive drugs and also during follow-up of patients with cGVHD may be considered.

  19. Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

    International Nuclear Information System (INIS)

    Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD

  20. Predictive Value of Bronchiolitis Obliterans Syndrome Stage 0p in Chronic Graft-versus-Host Disease of the Lung

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    Abedin, Sameem; Yanik, Gregory A.; Braun, Thomas; Pawarode, Attaphol; Magenau, John; Goldstein, Steven C.; Levine, John E.; Kitko, Carrie L.; Couriel, Daniel R.

    2016-01-01

    Bronchiolitis obliterans syndrome (BOS) is a significant post-transplant complication with low survival. BOS stage 0p (BOS 0p) is a parameter detected on pulmonary function tests (PFTs) after lung transplantation to identify patients at risk to develop BOS. We performed a retrospective study on 442 patients who underwent allogeneic stem cell transplant from 2007 to 2011 to evaluate whether development of BOS 0p is a risk factor in this population for BOS. Patients who met criteria for BOS 0p were significantly more likely to develop BOS (hazard ratio [HR], 3.22; P HR, 2.48; P =.001) and chronic graft-versus-host disease (GVHD) outside the lung post-transplant (HR, 23; P < .001). Finally, BOS 0p criteria were adequately sensitive in predicting BOS (85%), with a high negative predictive value (98%). Our findings suggest a routine PFT screening strategy with the intent of detecting BOS 0p, especially among patients with prior lung disease and who developed chronic GVHD, could suitably identify an at-risk population for the development of BOS. PMID:25687798

  1. Arresting rampant dental caries with silver diamine fluoride in a young teenager suffering from chronic oral graft versus host disease post-bone marrow transplantation: a case report

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    Chu, Chun-Hung; Lee, Angeline Hui-Cheng; Zheng, Liwu; Mei, May Lei; Chan, Godfrey Chi-fung

    2014-01-01

    BACKGROUND: Rampant caries is an advanced and severe dental disease that affects multiple teeth. This case describes the management of rampant caries in a young teenager suffering from chronic oral graft versus host disease after allogeneic bone marrow transplantation. CASE PRESENTATION: A 14-year-old Chinese boy suffering from beta-thalassemia major was referred to the dental clinic for the management of rampant dental caries. An oral examination revealed pale conjunctiva, bruising of lips, ...

  2. History of graft-versus-host disease.

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    Vriesendorp, Huib M; Heidt, Peter J

    2016-08-01

    Nuclear warfare at the end of World War II inspired Dick W. van Bekkum to study total-body irradiation (TBI) in animal models. After high-dose TBI, mice died from "primary disease" or bone marrow (BM) aplasia. Intravenous administration of allogeneic BM cells delayed mortality but did not prevent it. Initially the delayed deaths were said to be caused by "secondary disease," which was later renamed graft-versus-host disease (GvHD). GvHD is caused by donor T lymphocytes that destroy recipient cells in skin, intestinal mucosa, bile ducts, and lymph nodes. GvHD is opposed by host-versus-graft disease (HvGD), in which host T lymphocytes destroy the administered allogeneic BM cells, including the administered T lymphocytes of the BM donor. In 1960, van Bekkum became the director of the Radiobiological Institute of the Dutch Organization for Applied Scientific Research TNO, Rijswijk, The Netherlands, where he built a multidisciplinary team that defined the variables controlling the outcome of a BM transplant. The team published their early results in the Journal of Experimental Hematology [1981;9:904-916 and 1956;4:482-488]. Later, protocols were established for BM transplantation (BMT) in patients with severe combined immunodeficiency disease, leukemia, lymphoma, and other diseases of the hematopoietic system. This review honors the scientific contributions made by Dick van Bekkum and his team in defining the four dominant variables for improving the therapeutic ratio of allogeneic BMT and in fostering the international collaboration necessary to translate this knowledge into current clinical practice. PMID:27235758

  3. Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

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    Kheav, Vissal David; Busson, Marc; Scieux, Catherine; de Latour, Régis Peffault; Maki, Guitta; Haas, Philippe; Mazeron, Marie-Christine; Carmagnat, Maryvonnick; Masson, Emeline; Xhaard, Aliénor; Robin, Marie; Ribaud, Patricia; Dulphy, Nicolas; Loiseau, Pascale; Charron, Dominique; Socié, Gérard; Toubert, Antoine; Moins-Teisserenc, Hélène

    2014-01-01

    Natural killer cells are the first lymphocyte subset to reconstitute, and play a major role in early immunity after allogeneic hematopoietic stem cell transplantation. Cells expressing the activating receptor NKG2C seem crucial in the resolution of cytomegalovirus episodes, even in the absence of T cells. We prospectively investigated natural killer-cell reconstitution in a cohort of 439 adult recipients who underwent non-T-cell-depleted allogeneic hematopoietic stem cell transplantation between 2005 and 2012. Freshly collected blood samples were analyzed 3, 6, 12 and 24 months after transplantation. Data were studied with respect to conditioning regimen, source of stem cells, underlying disease, occurrence of graft-versus-host disease, and profiles of cytomegalovirus reactivation. In multivariate analysis we found that the absolute numbers of CD56bright natural killer cells at month 3 were significantly higher after myeloablative conditioning than after reduced intensity conditioning. Acute graft-versus-host disease impaired reconstitution of total and CD56dim natural killer cells at month 3. In contrast, high natural killer cell count at month 3 was associated with a lower incidence of chronic graft-versus-host disease, independently of a previous episode of acute graft-versus-host disease and stem cell source. NKG2C+CD56dim and total natural killer cell counts at month 3 were lower in patients with reactivation of cytomegalovirus between month 0 and month 3, but expanded greatly afterwards. These cells were also less numerous in patients who experienced later cytomegalovirus reactivation between month 3 and month 6. Our results advocate a direct role of NKG2C-expressing natural killer cells in the early control of cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation. PMID:25085354

  4. Preventing Graft-versus-Host Disease during Hemato

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    Researchers are investigating whether an immunosuppressive drug, sirolimus, can work with cyclosporine to prevent graft-versus-host disease (GVHD) more effectively than cyclosporine alone following allogeneic hematopoietic stem cell transplantation.

  5. Efficacy, durability, and response predictors of low-dose interleukin-2 therapy for chronic graft-versus-host disease.

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    Koreth, John; Kim, Haesook T; Jones, Kyle T; Lange, Paulina B; Reynolds, Carol G; Chammas, Marie J; Dusenbury, Katherine; Whangbo, Jennifer; Nikiforow, Sarah; Alyea, Edwin P; Armand, Philippe; Cutler, Corey S; Ho, Vincent T; Chen, Yi-Bin; Avigan, David; Blazar, Bruce R; Antin, Joseph H; Ritz, Jerome; Soiffer, Robert J

    2016-07-01

    Chronic graft-versus-host disease (cGVHD) is associated with inadequate reconstitution of tolerogenic CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs). Previous phase 1 studies identified a low daily dose of interleukin-2 (IL-2) that was well tolerated, did not exacerbate alloimmunity, augmented Treg in vivo, and was associated with improvement of active cGVHD. In the current phase 2 study, 35 adults with steroid-refractory cGVHD received daily IL-2 (1 × 10(6) IU/m(2)) for 12 weeks. Median time from transplantation and cGVHD onset was 616 days (range, 270-2145 days) and 317 days (range, 28-1880 days), respectively. Two patients withdrew and 5 required IL-2 dose reductions due to side effects. Twenty of 33 evaluable patients (61%) had clinical responses at multiple cGVHD sites (liver, skin, gastrointestinal tract, lung, joint/muscle/fascia). Three patients (9%) had progressive cGVHD. Compared with pretreatment levels, Treg and natural killer cell counts rose >fivefold (P fourfold (P fivefold (P < .001). Clinical responders initiated IL-2 earlier (508 vs 917 days after transplantation, P = .005; 249 vs 461 days after cGVHD onset; P = .03). Treg:Tcon ratios ≥0.07 at baseline and ≥0.2 at week 1 also predicted clinical response (P = .003; P = .0003, respectively). After a 4-week treatment hiatus, clinical responders were eligible to continue IL-2 therapy indefinitely. During 2 years of extended IL-2 therapy, clinical and Treg immune responses persisted, while Tcon count and Treg:Tcon ratio gradually normalized. Low-dose IL-2 provides durable clinical improvement in active cGVHD and extended therapy is well-tolerated. PMID:27073224

  6. Incidence and prognostic value of eosinophilia in chronic graft-versus-host disease after nonmyeloablative hematopoietic cell transplantation.

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    Ahmad, Imran; Labbé, Annie-Claude; Chagnon, Miguel; Busque, Lambert; Cohen, Sandra; Kiss, Thomas; Lachance, Silvy; Roy, Denis-Claude; Sauvageau, Guy; Roy, Jean

    2011-11-01

    Data from a number of cohorts indicate that eosinophilia (Eo) could be associated with better outcomes following allogeneic hematopoietic cell transplant (HCT). However, little is known about its significance and prognostic value in chronic graft-versus-host disease (cGVHD) after nonmyeloablative (NMA) transplantation. Data were collected from 170 patients who underwent HCT using the same preparative regimen and GVHD prophylaxis. Donors were 6/6 HLA-matched siblings and stem cell source was peripheral blood. An eosinophil count of ≥0.5 × 10(9)/L was defined as Eo. Patients were transplanted mainly for lymphoproliferative disorders. Median age and follow-up were 54 years and 58 months, respectively. Incidents of grade II-IV acute GVHD (aGVHD) and cGVHD were 8.2% and 81.2%. Median time from HCT to cGVHD diagnosis was 142 days. Organs involved were: mouth in 80% of patients, skin in 75%, liver in 57%, eyes in 37%, gut in 14%, lungs in 5%, others in 5%. Eo was found in 44% of patients at diagnosis of cGVHD (range: 0.5-4.4 × 10(9)/L). Median time between first appearance of Eo and diagnosis of cGVHD was 4.5 days. We found no correlation between organ involvement and Eo but a lower prevalence of Eo in cGVHD associated with thrombocytopenia (P = .023). Nevertheless, we observed no association among Eo and overall survival (OS), relapse incidence, or nonrelapse mortality (NRM) in the overall cohort, nor in subsets of patients with multiple myeloma and follicular non-Hodgkin lymphoma. Although Eo is observed frequently in cGVHD following NMA transplantation, we report no correlation beween Eo and outcome. PMID:21601640

  7. Increased serum IgE concentrations during infection and graft versus host disease after bone marrow transplantation.

    OpenAIRE

    Walker, S. A.; Rogers, T. R.; Perry, D; Hobbs, J R; Riches, P G

    1984-01-01

    Serum IgE concentrations estimated in 25 bone marrow transplant recipients during episodes of infection or graft versus host disease, or both, were raised not only in some patients with acute graft versus host disease but also in many patients with infection. Raised values were not seen in chronic graft versus host disease. The routine estimation of serum IgE in bone marrow transplant recipients had minimal value because of the lack of specificity of the IgE response.

  8. FDG PET/CT in Acute Tumefactive Multiple Sclerosis Occurring in a Case of Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Dong, Aisheng; Gao, Mingjun; Wang, Yang; Gao, Lei; Zuo, Changjing

    2016-09-01

    Tumefactive multiple sclerosis refers to the presentation of large demyelinating lesions (≥2 cm in diameter) mimicking brain tumors clinically and radiologically. We present the MRI and FDG PET/CT findings in a case with tumefactive multiple sclerosis, who had chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Head MRI showed 7 cerebral lesions with incomplete ring enhancement. All but one lesion had size more than 2 cm. All these demyelinating lesions showed increased uptake at the rims of the lesions with central hypometabolism. Stereotactic brain biopsy of the right frontal lesion revealed extensive macrophage and lymphocyte infiltration. PMID:26909714

  9. CIDP-like neuropathies in graft versus host disease.

    Science.gov (United States)

    Cocito, Dario; Romagnolo, Alberto; Rosso, Michela; Peci, Erdita; Lopiano, Leonardo; Merola, Aristide

    2015-03-01

    Cases of chronic inflammatory demyelinating poliradiculoneuropathy (CIDP) have been reported in hematopoietic stem cells transplantation complicated by graft versus host disease (GVHD). A systematic review of the CIDP-like neuropathies associated with GVHD was conducted until January 2015, analyzing the clinical presentation and the response to different therapeutic regimens. Nineteen patients have been reported in literature including the present one. Fourteen subjects fulfilled the criteria for CIDP, whereas two cases presented with an asymmetric motor onset and one showed motor involvement only associated with anti-ganglioside antibodies. In addition, two subjects already affected by CIDP developed a significant relapse after GVHD. This study reviews the literature data and reports one additional case of CIDP and GVHD, suggesting that the two clinical entities might share a similar immunological background. PMID:25864585

  10. Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease.

    Science.gov (United States)

    Pirsl, Filip; Curtis, Lauren M; Steinberg, Seth M; Tella, Sri Harsha; Katić, Mašenjka; Dobbin, Marnie; Hsu, Jennifer; Hakim, Fran T; Mays, Jacqueline W; Im, Annie P; Pulanić, Dražen; Mitchell, Sandra A; Baruffaldi, Judy; Masuch, Licia; Halverson, David C; Gress, Ronald E; Barsony, Julianna; Pavletic, Steven Z

    2016-08-01

    The National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Consensus Project Ancillary and Supportive Care Guidelines recommend annual assessment of bone mineral density (BMD) to monitor bone health. The study of osteoporosis in patients with cGVHD has been limited to small numbers of patients, and the guidelines are based on experience with other chronic diseases and expert opinion. We hypothesized that the prevalence of osteoporosis is high in a cohort of 258 patients with moderate to severe cGVHD because of prolonged exposure to risk factors for osteoporosis after allogeneic hematopoietic stem cell transplantation. We defined osteoporosis using BMD criteria (T-score ≤-2.5) at 3 anatomic sites-the femoral neck (FN), lumbar spine (LS), and total hip (TH)-and characterized risk factors through univariate and multivariate analyses. We found that low body weight (FN, P transplantation. PMID:27118572

  11. Soluble MICA-NKG2D interaction upregulates IFN-γ production by activated CD3-CD56+ NK cells: potential impact on chronic graft versus host disease.

    Science.gov (United States)

    Boukouaci, Wahid; Al-Daccak, Reem; Dulphy, Nicolas; Lauden, Laura; Amokrane, Kahina; Fortier, Catherine; Marzais, François; Bennabi, Meriem; Peffault de Latour, Regis; Socie, Gerard; Toubert, Antoine; Charron, Dominique; Krishnamoorthy, Rajagopal; Tamouza, Ryad

    2013-12-01

    A soluble isoform of MHC class I chain-related molecule A (soluble MICA), generated by proteolytic shedding from the membrane-bound MICA of various tumor cells, has been shown to downregulate both the expression of natural killer group 2-member D receptor and the cytotoxic function of effectors cells and was postulated as a mechanism for tumor immune evasion. Its effect on the expression of cytokines by the effector cells remained unexplored. Here we demonstrate that the sMICA molecules upregulate interferon gamma expression by interleukin-12/interleukin-18-activated CD3(-)CD56(+) natural killer cells, witnessing the pro-inflammatory effect of soluble MICA. Overall, these data are in line with our previous observations that the raised serum levels of soluble MICA, following allogeneic hematopoietic stem cell transplantation, confer susceptibility to and the presence of pre-transplantation anti-MICA antibodies in the patient's serum confer protection against chronic graft versus host disease.

  12. Clinical approach in the management of oral chronic graft-versus-host disease (cGVHD) in a series of specialized medical centers

    DEFF Research Database (Denmark)

    Elad, Sharon; Jensen, Siri Beier; Raber-Durlacher, Judith E;

    2015-01-01

    approaches used in the diagnosis and treatment of cGVHD in a group of health-care providers specialized in the oral care of oncology patients. The secondary objective was to assess the level of implementation of the National Institutes of Health (NIH) guidelines for cGVHD patients. METHODS: One hundred...... twenty questionnaires were sent to the members of the Oral Care Study Group (OCSG) of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The questionnaire included 50 questions about the responder's demographics, level of exposure to c......BACKGROUND: The oral cavity is frequently affected in chronic graft-versus-host disease (cGVHD), with variable clinical presentations. The literature on the effective management of patients suffering from oral cGVHD is limited. OBJECTIVE: The objective of this study was to assess the clinical...

  13. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2014 Biomarker Working Group Report.

    Science.gov (United States)

    Paczesny, Sophie; Hakim, Frances T; Pidala, Joseph; Cooke, Kenneth R; Lathrop, Julia; Griffith, Linda M; Hansen, John; Jagasia, Madan; Miklos, David; Pavletic, Steven; Parkman, Robertson; Russek-Cohen, Estelle; Flowers, Mary E D; Lee, Stephanie; Martin, Paul; Vogelsang, Georgia; Walton, Marc; Schultz, Kirk R

    2015-05-01

    Biology-based markers to confirm or aid in the diagnosis or prognosis of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation or monitor its progression are critically needed to facilitate evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biological or pathogenic process, or of a pharmacologic response to a therapeutic intervention. Applications of biomarkers in chronic GVHD clinical trials or patient management include the following: (1) diagnosis and assessment of chronic GVHD disease activity, including distinguishing irreversible damage from continued disease activity; (2) prognostic risk to develop chronic GVHD; and (3) prediction of response to therapy. Sample collection for chronic GVHD biomarkers studies should be well documented following established quality control guidelines for sample acquisition, processing, preservation, and testing, at intervals that are both calendar and event driven. The consistent therapeutic treatment of subjects and standardized documentation needed to support biomarker studies are most likely to be provided in prospective clinical trials. To date, no chronic GVHD biomarkers have been qualified for use in clinical applications. Since our previous chronic GVHD Biomarkers Working Group report in 2005, an increasing number of chronic GVHD candidate biomarkers are available for further investigation. This paper provides a 4-part framework for biomarker investigations: identification, verification, qualification, and application with terminology based on Food and Drug Administration and European Medicines Agency guidelines. PMID:25644957

  14. Beclomethasone in Treating Patients With Graft-Versus-Host Disease of the Esophagus, Stomach, Small Intestine, or Colon

    Science.gov (United States)

    2010-03-31

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Graft Versus Host Disease; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  15. Genetic risk factors for sclerotic graft-versus-host disease.

    Science.gov (United States)

    Inamoto, Yoshihiro; Martin, Paul J; Flowers, Mary E D; Lee, Stephanie J; Carpenter, Paul A; Warren, Edus H; Geraghty, Daniel E; Lee, Ni; Boeckh, Michael J; Storer, Barry E; Levine, David M; Fan, Wenhong; Zhao, Lue-Ping; Hansen, John A

    2016-09-15

    Sclerotic graft-versus-host disease (GVHD) is a distinctive phenotype of chronic GVHD after allogeneic hematopoietic cell transplantation, characterized by fibrosis of skin or fascia. Sclerotic GVHD has clinical and histopathological similarities with systemic sclerosis, an autoimmune disease whose risk is influenced by genetic polymorphisms. We examined 13 candidate single-nucleotide polymorphisms (SNPs) that have a well-documented association with systemic sclerosis to determine whether these SNPs are also associated with the risk of sclerotic GVHD. The study cohort included 847 consecutive patients who were diagnosed with chronic GVHD. Genotyping was performed using microarrays, followed by imputation of unobserved SNPs. The donor rs10516487 (BANK1: B-cell scaffold protein with ankyrin repeats 1) TT genotype was associated with lower risk of sclerotic GVHD (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.21-0.87; P = .02). Donor and recipient rs2056626 (CD247: T-cell receptor ζ subunit) GG or GT genotypes were associated with higher risk of sclerotic GVHD (HR, 1.57; 95% CI, 1.13-2.18; P = .007 and HR, 1.66; 95% CI, 1.19-2.32; P = .003, respectively). Donor and recipient rs987870 (5'-flanking region of HLA-DPA1) CC genotypes were associated with higher risk of sclerotic GVHD (HR, 2.50; 95% CI, 1.22-5.11; P = .01 and HR, 2.13; 95% CI, 1.00-4.54; P = .05, respectively). In further analyses, the recipient DPA1*01:03∼DPB1*04:01 haplotype and certain amino acid substitutions in the recipient P1 peptide-binding pocket of the HLA-DP heterodimer were associated with risk of sclerotic GVHD. Genetic components associated with systemic sclerosis are also associated with sclerotic GVHD. HLA-DP-mediated antigen presentation, T-cell response, and B-cell activation have important roles in the pathogenic mechanisms of both diseases. PMID:27313329

  16. Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease.

    Science.gov (United States)

    Laverdière, Isabelle; Guillemette, Chantal; Tamouza, Ryad; Loiseau, Pascale; Peffault de Latour, Regis; Robin, Marie; Couture, Félix; Filion, Alain; Lalancette, Marc; Tourancheau, Alan; Charron, Dominique; Socié, Gérard; Lévesque, Éric

    2015-02-01

    Effective immunosuppression is mandatory to prevent graft-versus-host disease and to achieve a successful clinical outcome of hematopoietic stem cell transplantation. Here we tested whether germline single nucleotide polymorphisms in 20 candidate genes related to methotrexate and cyclosporine metabolism and activity influence the incidence of graft-versus-host disease in patients who undergo stem cell transplantation for hematologic disorders. Recipient genetic status of the adenosine triphosphate-binding cassette sub-family C1 and adenosine triphosphate-binding cassette sub-family C2 transporters, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ inosine monophosphate cyclohydrolase within the methotrexate pathway, and nuclear factor of activated T cells (cytoplasmic 1) loci exhibit a remarkable influence on severe acute graft-versus-host disease prevalence. Indeed, an increased risk of acute graft-versus-host disease was observed in association with single nucleotide polymorphisms located in 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (hazard ratio=3.04; P=0.002), nuclear factor of activated T cells (cytoplasmic 1) (hazard ratio=2.69; P=0.004), adenosine triphosphate-binding cassette sub-family C2 (hazard ratio=3.53; P=0.0018) and adenosine triphosphate-binding cassette sub-family C1 (hazard ratio=3.67; P=0.0005). While donor single nucleotide polymorphisms of dihydrofolate reductase and solute carrier family 19 (member 1) genes are associated with a reduced risk of acute graft-versus-host disease (hazard ratio=0.32-0.41; P=0.0009-0.008), those of nuclear factor of activated T cells (cytoplasmic 2) are found to increase such risk (hazard ratio=3.85; P=0.0004). None of the tested single nucleotide polymorphisms was associated with the occurrence of chronic graft-versus-host disease. In conclusion, by targeting drug-related biologically relevant genes, this work emphasizes the potential role of

  17. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research.

    Science.gov (United States)

    Arai, Sally; Arora, Mukta; Wang, Tao; Spellman, Stephen R; He, Wensheng; Couriel, Daniel R; Urbano-Ispizua, Alvaro; Cutler, Corey S; Bacigalupo, Andrea A; Battiwalla, Minoo; Flowers, Mary E; Juckett, Mark B; Lee, Stephanie J; Loren, Alison W; Klumpp, Thomas R; Prockup, Susan E; Ringdén, Olle T H; Savani, Bipin N; Socié, Gérard; Schultz, Kirk R; Spitzer, Thomas; Teshima, Takanori; Bredeson, Christopher N; Jacobsohn, David A; Hayashi, Robert J; Drobyski, William R; Frangoul, Haydar A; Akpek, Görgün; Ho, Vincent T; Lewis, Victor A; Gale, Robert Peter; Koreth, John; Chao, Nelson J; Aljurf, Mahmoud D; Cooper, Brenda W; Laughlin, Mary J; Hsu, Jack W; Hematti, Peiman; Verdonck, Leo F; Solh, Melhelm M; Norkin, Maxim; Reddy, Vijay; Martino, Rodrigo; Gadalla, Shahinaz; Goldberg, Jenna D; McCarthy, Philip L; Pérez-Simón, José A; Khera, Nandita; Lewis, Ian D; Atsuta, Yoshiko; Olsson, Richard F; Saber, Wael; Waller, Edmund K; Blaise, Didier; Pidala, Joseph A; Martin, Paul J; Satwani, Prakash; Bornhäuser, Martin; Inamoto, Yoshihiro; Weisdorf, Daniel J; Horowitz, Mary M; Pavletic, Steven Z

    2015-02-01

    Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.

  18. Fulminant transfusion-associated graft-versus-host disease in a premature infant

    International Nuclear Information System (INIS)

    A fatal case of transfusion-associated graft-versus-host disease developed in a premature infant after receiving several blood products, including nonirradiated white blood cells. Transfusion-associated graft-versus-host disease can be prevented. Irradiation of blood products is the least controversial and most effective method. Treatment was unsuccessful in most reported cases of transfusion-associated graft-versus-host disease. Therefore irradiation of blood products before transfusing to patients susceptible to transfusion-associated graft-versus-host disease is strongly recommended

  19. Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

    Energy Technology Data Exchange (ETDEWEB)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1982-04-01

    The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis.

  20. Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

    International Nuclear Information System (INIS)

    The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis

  1. Translation, Cross-Cultural Adaptation, and Validation of the Lee Chronic Graft-versus-Host Disease Symptom Scale in a Brazilian Population.

    Science.gov (United States)

    Vasconcellos de Souza, Clarissa; Vigorito, Afonso Celso; Miranda, Eliana C M; Garcia, Celso; Rensi Colturato, Vergílio Antonio; Mauad, Marcos Augusto; Rodrigues Moreira, Maria Cláudia; da Silva Bouzas, Luis Fernando; Lermontov, Simone; Hamerschlak, Nelson; Rodrigues, Morgani; Carlos de Almeida Barros, Jose; Chiattone, Ricardo; Lee, Stephanie J; Flowers, Mary E D

    2016-07-01

    The Lee Chronic Graft-versus-Host Disease (GVHD) Symptom Scale is a patient-reported instrument developed and validated in English to measure the symptoms and functional impact of cGVHD. This tool has not yet been validated in a Latin American population, however. The Brazil-Seattle Chronic GVHD Consortium conducted a multicenter study at 5 Brazilian institutions to validate the Lee cGVHD Symptom Scale in adults with cGVHD. Study objectives included the translation and validation of the instrument in Brazilian Portuguese and evaluation of the correlation with other quality of life (QoL) tools, including the Medical Outcomes Study Short Form 36 (SF-36) and Functional Assessment of Chronic Illness Therapy with Bone Marrow Transplant subscale (FACT-BMT). Translation and validation were done according to the American Association of Orthopedic Surgeons Outcome Committee guidelines. Spearman's correlation coefficient was used to measure construct validity. Reliability was assessed using Cronbach's α and intraclass correlation coefficients. Between April 2011 and August 2012, 47 patients with cGVHD based on the 2005 National Institutes of Health criteria (29 males [62%], 18 females [38%]; median age, 48 years; range, 23 to 69 years) were enrolled in this study. The reliability of the Lee cGVHD Symptom Scale was adequate (Cronbach's α = 0.62 to 0.83). The correlations between similar domains of the Lee cGVHD Symptom Scale, SF-36, and FACT-BMT were moderate to high. Our data indicate that the Brazilian Portuguese version of the Lee cGVHD Symptom Scale is valid and reliable and can be used in clinical trials of cGVHD in Brazil. PMID:27058616

  2. Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice.

    Directory of Open Access Journals (Sweden)

    Steven D Schutt

    Full Text Available Bruton's Tyrosine Kinase (BTK and IL-2 Inducible T-cell Kinase (ITK are enzymes responsible for the phosphorylation and activation of downstream effectors in the B-cell receptor (BCR signaling and T cell receptor (TCR signaling pathways, respectively. Ibrutinib is an FDA-approved potent inhibitor of both BTK and ITK that impairs B-cell and T-cell function. CD4 T cells and B cells are essential for the induction of chronic graft-versus-host disease (cGVHD. We evaluated these targets by testing the ability of Ibrutinib to prevent or ameliorate cGVHD, which is one of the major complications for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT. We found that Ibrutinib significantly alleviated cGVHD across four different mouse models, accompanied by increased long-term survival and reduced clinical score. The clinical improvements in Ibrutinib-treated recipients were associated with decreased serum-autoantibodies, costimulatory molecule activation, B-cell proliferation, and glomerulonephritis compared to vehicle controls. Ibrutinib was also able to alleviate the clinical manifestations in acute GVHD (aGVHD, where the recipients were given grafts with or without B cells, suggesting that an inhibitory effect of Ibrutinib on T cells contributes to a reduction in both aGVHD and cGVHD pathogenesis. An effective prophylactic regimen is still lacking to both reduce the incidence and severity of human cGVHD following allo-HSCT. Our study shows that Ibrutinib is an effective prophylaxis against several mouse models of cGVHD with minimal toxicity and could be a promising strategy to combat human cGVHD clinically.

  3. Pneumatosis cystoides interstitialis: A complication of graft-versus-host disease. A report of two cases

    International Nuclear Information System (INIS)

    Pneumatosis cystoides intestinalis (PCI) is a rare disorder characterized by the presence of multiple gas collections in the subserosal or submucosal intestinal wall of the large or small intestine. We report two cases of PCI in the course of chronic graft-versus-host disease. A 5-year-old girl was treated for acute lymphoblastic leukemia. Twenty-four months after the hematopoietic stem cell transplantation, in the course of graft-versus-host disease, she developed subcutaneous emphysema of the right inguinal and pudendal region. PCI was diagnosed based on a CT examination. A 3-year-old boy was treated for juvenile myelomonocytic leukemia. Fourteen months after the hematopoietic stem cell transplantation he presented with an increased severity of intestinal symptoms, including intermittent bleeding from large intestine. PCI was diagnosed based on a CT exam and was confirmed by a colonoscopy. Pneumatosis cystoides interstitialis in the course of chronic graft-versus-host disease has a heterogeneous clinical presentation that does not correlate with results of imaging. CT is a method of choice to diagnose PCI. In patients with PCI, the presence of free air in the peritoneal cavity does not confirm an intestinal perforation

  4. Cytokine profile of autologous platelet-derived eye drops in patients with ocular chronic graft-versus-host disease.

    Science.gov (United States)

    Valentini, C G; Nuzzolo, E R; Orlando, N; Metafuni, E; Bianchi, M; Chiusolo, P; Zini, G; Teofili, L

    2016-02-01

    Ocular chronic GVHD is efficaciously treated with autologous platelet-derived eye drops. We investigated the cytokine content of eye drops produced using a non-gelified lysate obtained from autologous platelet-rich plasma in six patients with ocular GVHD. In both the responding (n = 4) and the resistant (n = 2) patients, the eye drops were significantly enriched with various growth factors, in amounts proportional with the platelet counts. In contrast, chemokine ligand and interleukin levels were similar to those of plasma. The non-responding patients showed the highest levels of chemokine (C-X-C motif) ligand (CXCL)10. These findings provide possible explanations for beneficial or detrimental effects of eye drops. PMID:26383050

  5. Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation – A Report from CIBMTR

    Science.gov (United States)

    Arai, Sally; Arora, Mukta; Wang, Tao; Spellman, Stephen R.; He, Wensheng; Couriel, Daniel R.; Urbano-Ispizua, Alvaro; Cutler, Corey S.; Bacigalupo, Andrea A.; Battiwalla, Minoo; Flowers, Mary E.; Juckett, Mark B.; Lee, Stephanie J.; Loren, Alison W.; Klumpp, Thomas R.; Prockup, Susan E.; Ringdén, Olle T.H.; Savani, Bipin N.; Socié, Gérard; Schultz, Kirk R.; Spitzer, Thomas; Teshima, Takanori; Bredeson, Christopher N.; Jacobsohn, David A.; Hayashi, Robert J.; Drobyski, William R.; Frangoul, Haydar A.; Akpek, Görgün; Ho, Vincent T.; Lewis, Victor A.; Gale, Robert Peter; DSc(hon); Koreth, John; Chao, Nelson J.; Aljurf, Mahmoud D.; Cooper, Brenda W.; Laughlin, Mary J.; Hsu, Jack W.; Hematti, Peiman; Verdonck, Leo F.; Solh, Melhelm M.; Norkin, Maxim; Reddy, Vijay; Martino, Rodrigo; Gadalla, Shahinaz; Goldberg, Jenna D.; McCarthy, Philip L.; Pérez-Simón, José A.; Khera, Nandita; Lewis, Ian D.; Atsuta, Yoshiko; Olsson, Richard F.; Saber, Wael; Waller, Edmund K.; Blaise, Didier; Pidala, Joseph A.; Martin, Paul J.; Satwani, Prakash; Bornhäuser, Martin; Inamoto, Yoshihiro; Weisdorf, Daniel J.; Horowitz, Mary M.; Pavletic, Steven Z.

    2015-01-01

    Although transplant practices have changed over the last decades there is no information on trends in incidence and outcome of cGVHD over time. This study utilized the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe the time trends for cGVHD incidence, non-relapse mortality, and the risk factors for cGVHD. The 12-year period was divided into three intervals: 1995-1999, 2000-2003, 2004-2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndrome. In the multivariate analysis, the incidence of cGVHD was shown to be increased in more recent years (odds ratio= 1.19, p<0.0001) and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, non-relapse mortality has decreased over time, but at 5-years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. PMID:25445023

  6. Novel regulatory therapies for prevention of Graft-versus-host disease

    Directory of Open Access Journals (Sweden)

    Leventhal Joseph

    2012-05-01

    Full Text Available Abstract Graft-versus-host disease is one of the major transplant-related complications in allogeneic hematopoietic stem cell transplantation. Continued efforts have been made to prevent the occurrence of severe graft-versus-host disease by eliminating or suppressing donor-derived effector T cells. Conventional immunosuppression does not adequately prevent graft-versus-host disease, especially in mismatched transplants. Unfortunately, elimination of donor-derived T cells impairs stem cell engraftment, and delays immunologic reconstitution, rendering the recipient susceptible to post-transplant infections and disease relapse, with potentially lethal consequences. In this review, we discuss the role of dynamic immune regulation in controlling graft-versus-host disease, and how cell-based therapies are being developed using regulatory T cells and other tolerogenic cells for the prevention and treatment of graft-versus-host disease. In addition, advances in the design of cytoreductive conditioning regimens to selectively target graft-versus-host disease-inducing donor-derived T cells that have improved the safety of allogeneic stem cell transplantation are reviewed. Finally, we discuss advances in our understanding of the tolerogenic facilitating cell population, a phenotypically and functionally distinct population of bone marrow-derived cells which promote hematopoietic stem cell engraftment while reducing the risk of graft-versus-host disease.

  7. [Chemokine Receptor-5 and Graft-versus-Host Disease].

    Science.gov (United States)

    Yuan, Jing; Liu, Wei; Ren, Han-Yun

    2015-06-01

    Chemokine receptor-5 (CCR5) belongs to a G-protein coupled receptors superfamily. It is mainly expressed on a wide variety of immune cells. CCR5 can bind with its specific ligands, which plays very important roles in inflammatory cell growth, differentiation, activation, adhesion and migration. CCR5 was identified as a co-receptor for human immunodeficiency virus type-1 (HIV-1) to infect CD4+ T cells. In addition, CCR5 not only participates in the pathogenic mechanisms of many inflammation disease such as AIDS, auto-immune disease, and atherosclerosis, but also plays important roles in the development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Recent studies using murine models have demonstrated the critical role of CCR5 and its ligands which direct T-cell infiltration and recruitment into target tissues during acute GVHD. CCR5 has become the focus of intense interest and discussion, and this review will attempt to describe what is understood about the structure and function, internalization, signal transduction of CCR5, in order to investigate the relationship between CCR5 and acute GVHD. PMID:26117055

  8. Fototerapia na doença enxerto contra hospedeiro Phototherapy in the graft versus host disease

    Directory of Open Access Journals (Sweden)

    Ida Duarte

    2008-10-01

    Full Text Available FUNDAMENTOS: A doença enxerto contra hospedeiro é um dos obstáculos ao sucesso do transplante de medula óssea, e o envolvimento cutâneo é freqüente. A fototerapia é utilizada devido à intensa atividade imunomoduladora local, sendo opção terapêutica adjuvante para as lesões cutâneas resistentes à terapia convencional. OBJETIVO: Realizar análise descritiva do tratamento da doença enxerto contra hospedeiro com fototerapia (Puva ou UVB de faixa estreita. MÉTODOS: Foram atendidos nove pacientes com manifestação cutânea da doença enxerto contra hospedeiro aguda ou crônica. Seis foram tratados com Puva, terapia de primeira escolha, e três com UVB de faixa estreita. As sessões foram realizadas três vezes por semana, e a resposta terapêutica avaliada após 12 sessões. RESULTADOS: Todos os pacientes com doença enxerto contra hospedeiro aguda mostraram melhora, com desaparecimento do eritema e do edema. Naqueles com doença crônica, observaram-se involução das lesões liquenóides e melhora da mobilidade daqueles com a forma esclerodermiforme. Dois pacientes apresentaram doença de evolução grave e foram a óbito. CONCLUSÃO: A fototerapia mostrou-se efetiva no tratamento das manifestações cutâneas da doença enxerto contra hospedeiro aguda e crônica. A Puva permite o controle da doença, podendo a UVB de faixa estreita ser opção para pacientes impossibilitados de usar medicação sistêmica.BACKGROUND: Graft versus host disease is one of the obstacles to successful bone marrow transplantation. It often affects the skin. Phototherapy has been used because of its strong local immunomodulatory activity and it is an option for adjuvant therapy for skin lesions of graft versus host disease resistant to conventional therapy. OBJECTIVE: To make a descriptive analysis of treating graft versus host disease with phototherapy (PUVA or narrowband UVB. Methods - Nine patients with cutaneous manifestation of acute or chronic

  9. Pathogenic mechanisms of Acute Graft versus Host Disease

    Directory of Open Access Journals (Sweden)

    Ferrara James L.M.

    2002-01-01

    Full Text Available Graft-versus-host-disease (GVHD is the major complication of allogeneic Bone Marrow Transplant (BMT. Older BMT recipients are a greater risk for acute GVHD after allogeneic BMT, but the causes of this association are poorly understood. Using well-characterized murine BMT models we have explored the mechanisms of increased GVHD in older mice. GVHD mortality and morbidity, and pathologic and biochemical indices were all worse in old recipients. Donor T cell responses were significantly increased in old recipients both in vivo and in vitro when stimulated by antigen-presenting cells (APCs from old mice. In a haploidential GVHD model, CD4+ donor T cells mediated more severe GVHD in old mice. We confirmed the role of aged APCs in GVHD using bone marrow chimera recipient created with either old or young bone marrow. APCs from these mice also stimulated greater responses from allogeneic cells in vitro. In a separate set of experiments we evaluated whether alloantigen expression on host target epithelium is essential for tissue damage induced by GVHD. Using bone marrow chimeras recipients in which either MHC II or MHC I alloantigen was expressed only on APCs, we found that acute GVHD does not require alloantigen expression on host target epithelium and that neutralization of tumor necrosis factor-alpha and interleukin-1 prevents acute GVHD. These results pertain to CD4-mediated GVHD and to a lesser extent in CD8-mediated GVHD, and confirm the central role of most APCs as well as inflammatory cytokines.

  10. A Single-Center Pilot Prospective Study of Topical Application of Platelet-Derived Eye Drops for Patients with Ocular Chronic Graft-versus-Host Disease.

    Science.gov (United States)

    Zallio, Francesco; Mazzucco, Laura; Monaco, Federico; Astori, Maria Rosa; Passera, Roberto; Drago, Giovanna; Tamiazzo, Stefania; Rapetti, Manuela; Dolcino, Daniela; Guaschino, Roberto; Pini, Massimo; Ladetto, Marco

    2016-09-01

    Ocular involvement of chronic graft-versus-host disease (cGVHD) is a complication that occurs in up to 60% of patients after allogeneic hematopoietic stem cell transplantation. Conventional therapeutic options include medical and surgical procedures that are administered depending on the severity of the condition, but most of them have provided unsatisfactory results and, to date, there is no consensus about treatment. We considered that topical application of a platelet lysate, administered as eye drops, might be considered an alternative worthwhile of investigation to treat ocular surface disorders in patients suffering from cGVHD. Therefore, we conducted a single-center prospective pilot study to assess the efficacy and safety of using eye drops made from reconstituted lysed platelet concentrate. Twenty-six patients with ocular cGVHD were eligible for the study; all but 2 completed their scheduled 1-year treatment and complied with the hematologic and ophthalmic regimen. At their first assessment interviews, after 30 days of treatment, 91% of patients reported an improvement in their symptoms and for 32%, substantive objective differences were measured. Remission of corneal damage was seen for 86% of our cohort, and improved National Institutes of Health scores for 73%, of whom 8% achieved the best score of 0 (ie, non-dry eye). Similar results were seen at later time points. Comparing outcomes for our patient cohort to those determined retrospectively for patients in our institutional database revealed a 5-year overall survival (OS) of 65%. This OS is comparable to patients with limited cGVHD (75%) and is superior to that of patients with nonocular extensive cGVHD or without cGVHD (30% and 59%, respectively) (P = .013). Our results suggest that platelet-derived eye drops are a safe, practical, and well-tolerated therapeutic option that offers substantial benefits for most patients affected by ocular cGVHD at onset. The favorable OS of our patient cohort

  11. Graft-versus-host disease: unexpected presentation with simultaneous hepatitis and pancreatitis.

    Science.gov (United States)

    Fernandes, Samuel Raimundo; Alves, Antonio T; Cortes, Margarida Barreto; Cortez-Pinto, Helena

    2016-01-01

    We report the case of a 37-year-old man with a previous bone marrow transplantation presenting with abdominal pain, diarrhoea and jaundice. Laboratory evaluation showed marked elevated liver enzymes, amylase and lipase with ultrasonographic evidence of acute alithiasic pancreatitis. Liver biopsy was compatible with graft-versus-host disease and toxic hepatitis. The patient rapidly improved after increasing immunosuppression. Although gastrointestinal manifestations are common in graft-versus-host disease, clinical acute pancreatitis is rarely seen. Patients with graft versus host are seldom managed by gastroenterologists and hepatologists. An awareness of this condition is essential for the experienced clinician. PMID:27485875

  12. The Gut Microbiota and Immune System Relationship in Human Graft-versus-Host Disease

    OpenAIRE

    Laterza, Lucrezia; Rizzatti, Gianenrico; Gaetani, Eleonora; Chiusolo, Patrizia; Gasbarrini, Antonio

    2016-01-01

    Gut microbiota has gained increasing interest in the pathogenesis of immune-related diseases. In this context, graft-versus-host disease is a condition characterized by an immune response which frequently complicates and limits the outcomes of hematopoietic stem cell transplantations. Past studies, carried mostly in animals, already supported a relationship between gut microbiota and graft-versus-host disease. However, the possible mechanisms underlying this connection remain elusory. Moreove...

  13. Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease

    OpenAIRE

    Laverdière, Isabelle; Guillemette, Chantal; Tamouza, Ryad; Loiseau, Pascale; de Latour, Regis Peffault; Robin, Marie; Couture, Félix; Filion, Alain; Lalancette, Marc; Tourancheau, Alan; Charron, Dominique; Socié, Gérard; Lévesque, Éric

    2015-01-01

    Effective immunosuppression is mandatory to prevent graft-versus-host disease and to achieve a successful clinical outcome of hematopoietic stem cell transplantation. Here we tested whether germline single nucleotide polymorphisms in 20 candidate genes related to methotrexate and cyclosporine metabolism and activity influence the incidence of graft-versus-host disease in patients who undergo stem cell transplantation for hematologic disorders. Recipient genetic status of the adenosine triphos...

  14. Heparanase promotes engraftment and prevents graft versus host disease in stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Menachem Bitan

    Full Text Available BACKGROUND: Heparanase, endoglycosidase that cleaves heparan sulfate side chains of heparan sulfate proteoglycans, plays important roles in cancer metastasis, angiogenesis and inflammation. DESIGN AND METHODS: Applying a mouse model of bone marrow transplantation and transgenic mice over-expressing heparanase, we evaluated the effect of heparanase on the engraftment process and the development of graft-versus-host disease. RESULTS: Analysis of F1 mice undergoing allogeneic bone marrow transplantation from C57BL/6 mice demonstrated a better and faster engraftment in mice receiving cells from donors that were pretreated with heparanase. Moreover, heparanase treated recipient F1 mice showed only a mild appearance of graft-versus-host disease and died 27 days post transplantation while control mice rapidly developed signs of graft-versus-host disease (i.e., weight loss, hair loss, diarrhea and died after 12 days, indicating a protective effect of heparanase against graft-versus-host disease. Similarly, we applied transgenic mice over-expressing heparanase in most tissues as the recipients of BMT from C57BL/6 mice. Monitoring clinical parameters of graft-versus-host disease, the transgenic mice showed 100% survival on day 40 post transplantation, compared to only 50% survival on day 14, in the control group. In vitro and in vivo studies revealed that heparanase inhibited T cell function and activation through modulation of their cytokine repertoire, indicated by a marked increase in the levels of Interleukin-4, Interleukin-6 and Interleukin-10, and a parallel decrease in Interleukin-12, tumor necrosis factor-alfa and interferon-gamma. Using point mutated inactive enzyme, we found that the shift in cytokine profile was independent of heparanase enzymatic activity. CONCLUSIONS: Our results indicate a significant role of heparanase in bone marrow transplantation biology, facilitating engraftment and suppressing graft-versus-host disease, apparently

  15. Impact of graft versus host disease on outcome of allogeneic peripherial blood stem cell transplantation for leukemia

    Institute of Scientific and Technical Information of China (English)

    黎美章

    2014-01-01

    Objective To analyze the impact of the occurrence and severity of acute and chronic graft versus host disease(GVHD)on the long-term outcome of allogeneic peripheral blood stem cell transplantation(allo-PBSCT)for leukemia.Methods A total of 231 patients with leukemia,who underwent allo-HSCT in Changhai Hospital from Jan1st,2001 to Dec 31th,2011,were retrospectively analyzed.The overall survival(OS),disease-free survival

  16. Doença enxerto versus hospedeiro aguda A- GVHD Acute graft-versus-host disease

    Directory of Open Access Journals (Sweden)

    Wellington Azevedo

    2010-05-01

    Full Text Available A doença enxerto contra hospedeiro aguda (A-GVHD é síndrome sistêmica que acomete pacientes transplantados de medula óssea que recebem linfócitos imuno-competentes. A fisiopatologia do fenômeno é complexa e envolve uma série de respostas de diversos efetores imunológicos a estímulos antigênicos naturais ou que são expressos devido ao dano tecidual provocado pela doença ou pelo condicionamento. A ocorrência desta complicação é frequente em transplantes de medula óssea e determina, em grande parte, a evolução clínica do paciente. Neste capítulo são discutidos aspectos da biologia da doença do enxerto versus hospedeiro aguda, da sua evolução clínica e do manejo profilático e terapêutico deste problema, que pode ser devastador para pacientes submetidos a transplantes alogênicos de medula óssea.Graft versus host disease (A-GVHD is a systemic disease that affects bone marrow transplant patients receiving immunocompetent lymphocytes. The pathophysiology of this phenomenon is complex and involves a number of different effector immune responses to antigenic stimuli that are expressed due to tissue damage caused by disease or conditioning. This complication is frequent in bone marrow transplants and often determines the clinical outcome. In this chapter we discuss aspects of the biology of chronic graft versus host disease, its clinical evolution and the prophylactic and therapeutic management of this problem which can be devastating for patients undergoing allogeneic bone marrow transplantation.

  17. Autoimmune Demyelinating Polyneuropathy as a Manifestation of Chronic Graft-versus-Host Disease after Adult Cord Blood Transplantation in a Patient with Chronic Lymphocytic Leukemia

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    Fredrick Hogan

    2014-01-01

    Full Text Available Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP has been reported after related and adult unrelated allogeneic stem cell transplantation but no such case has been reported after unrelated cord blood transplantation. We hereby present the first case of AIDP after double umbilical cord blood transplantation (DUCBT. A 55-year-old man with chronic lymphocytic leukemia (CLL received a cord blood transplant for relapsed refractory disease with high risk cytogenetics. On day 221, patient presented with skin rash, tingling in both lower extremites, and ascending paralysis that progressed rapidly over the course of 2 days. The workup resulted in a diagnosis of AIDP and administration of intravenous immunoglobulins plus steroids was initiated. Motor and sensory powers were fully recovered and his chronic GVHD was managed for several months with single agent sirolimus.

  18. Chronic inflammatory demyelinating polyradiculoneuropathy in chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: case report Polirradiculoneuropatia desmielinizante inflamatória crônica na doença do enxerto contra o hospedeiro após transplante de células hematopoiéticas alogênicas: relato de caso

    OpenAIRE

    Paulo José Lorenzoni; Rosana Herminia Scola; Ana Lucila Moreira Carsten; Ana Paula Trentin; Hélio A.G. Teive; Ricardo Pasquini; Lineu C. Werneck

    2007-01-01

    The chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an unusual but important complication of hematopoietic stem cell transplantation (HSCT) rarely reported to date. We describe a 17-year-old woman with a diagnosis of acute myeloid leukemia due to Fanconi's anemia who was submitted to allogeneic HSCT and developed CIDP as part of graft-versus-host disease. Investigation showed high cerebrospinal fluid protein; electrophysiological studies revealed sensory-motor demyelinatin...

  19. Bilateral Sequential Dacryocystitis in a Patient With Graft-Versus-Host Disease.

    Science.gov (United States)

    Campbell, Ashley A; Jakobiec, Frederick A; Rashid, Alia; Dana, Reza; Yoon, Michael K

    2016-01-01

    A 29-year-old woman with a history of 2 bone marrow transplants for acute myelogenous leukemia developed bilateral sequential dacryocystitis in the context of known ocular graft-versus-host disease. With each infection, the patient underwent uneventful dacryocystorhinostomy. Postoperatively, she developed severe dry eye disease requiring replacement of punctal plugs and use of a prosthetic replacement of the ocular surface ecosystem lens. Histopathologic and immunohistochemical examination of the lacrimal sac showed a dense diffuse nonfollicular lymphocytic subepithelial infiltrate in the lacrimal sac that contained moderately more T-cells than B-cells. This is the first report of acute dacryocystitis associated with graft-versus-host disease. The authors caution that similar patients may develop worsening of ocular surface dryness due to restoration of normal lacrimal outflow. PMID:25192327

  20. MicroRNAs: The Missing Link in the Biology of Graft-Versus-Host Disease?

    OpenAIRE

    Atarod, Sadaf; Dickinson, Anne Mary

    2013-01-01

    Graft-versus-host disease (GVHD) is still the major complication of allogeneic hematopoietic stem cell transplantation. Despite extensive studies in understanding the pathophysiology of GVHD, its pathogenesis remains unclear. Recently, important functions of microRNAs have been demonstrated in various autoimmune diseases and cancers such as psoriasis and lymphoma. This review highlights the need to investigate the role of microRNAs in GVHD and hypothesizes that microRNAs may be one of the mis...

  1. Heparanase Promotes Engraftment and Prevents Graft versus Host Disease in Stem Cell Transplantation

    OpenAIRE

    Menachem Bitan; Lola Weiss; Michael Zeira; Eyal Zcharia; Shimon Slavin; Arnon Nagler; Israel Vlodavsky

    2010-01-01

    BACKGROUND: Heparanase, endoglycosidase that cleaves heparan sulfate side chains of heparan sulfate proteoglycans, plays important roles in cancer metastasis, angiogenesis and inflammation. DESIGN AND METHODS: Applying a mouse model of bone marrow transplantation and transgenic mice over-expressing heparanase, we evaluated the effect of heparanase on the engraftment process and the development of graft-versus-host disease. RESULTS: Analysis of F1 mice undergoing allogeneic bone marrow transpl...

  2. Hydrogen, a potential safeguard for graft-versus-host disease and graft ischemia-reperfusion injury?

    Science.gov (United States)

    Yuan, Lijuan; Shen, Jianliang

    2016-01-01

    Post-transplant complications such as graft-versus-host disease and graft ischemia-reperfusion injury are crucial challenges in transplantation. Hydrogen can act as a potential antioxidant, playing a preventive role against post-transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on graft ischemia-reperfusion injury and graft-versus-host disease. Existing data on the effects of hydrogen on ischemia-reperfusion injury related to organ transplantation are specifically reviewed and coupled with further suggestions for future work. The reviewed studies showed that hydrogen (inhaled or dissolved in saline) improved the outcomes of organ transplantation by decreasing oxidative stress and inflammation at both the transplanted organ and the systemic levels. In conclusion, a substantial body of experimental evidence suggests that hydrogen can significantly alleviate transplantation-related ischemia-reperfusion injury and have a therapeutic effect on graft-versus-host disease, mainly via inhibition of inflammatory cytokine secretion and reduction of oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for hydrogen use as a drug in the clinic.

  3. Hydrogen, a potential safeguard for graft-versus-host disease and graft ischemia-reperfusion injury?

    Science.gov (United States)

    Yuan, Lijuan; Shen, Jianliang

    2016-09-01

    Post-transplant complications such as graft-versus-host disease and graft ischemia-reperfusion injury are crucial challenges in transplantation. Hydrogen can act as a potential antioxidant, playing a preventive role against post-transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on graft ischemia-reperfusion injury and graft-versus-host disease. Existing data on the effects of hydrogen on ischemia-reperfusion injury related to organ transplantation are specifically reviewed and coupled with further suggestions for future work. The reviewed studies showed that hydrogen (inhaled or dissolved in saline) improved the outcomes of organ transplantation by decreasing oxidative stress and inflammation at both the transplanted organ and the systemic levels. In conclusion, a substantial body of experimental evidence suggests that hydrogen can significantly alleviate transplantation-related ischemia-reperfusion injury and have a therapeutic effect on graft-versus-host disease, mainly via inhibition of inflammatory cytokine secretion and reduction of oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for hydrogen use as a drug in the clinic. PMID:27652837

  4. Mouse models of graft-versus-host disease: advances and limitations

    Directory of Open Access Journals (Sweden)

    Mark A. Schroeder

    2011-05-01

    Full Text Available The limiting factor for successful hematopoietic stem cell transplantation (HSCT is graft-versus-host disease (GvHD, a post-transplant disorder that results from immune-mediated attack of recipient tissue by donor T cells contained in the transplant. Mouse models of GvHD have provided important insights into the pathophysiology of this disease, which have helped to improve the success rate of HSCT in humans. The kinetics with which GvHD develops distinguishes acute from chronic GvHD, and it is clear from studies of mouse models of GvHD (and studies of human HSCT that the pathophysiology of these two forms is also distinct. Mouse models also further the basic understanding of the immunological responses involved in GvHD pathology, such as antigen recognition and presentation, the involvement of the thymus and immune reconstitution after transplantation. In this Perspective, we provide an overview of currently available mouse models of acute and chronic GvHD, highlighting their benefits and limitations, and discuss research and clinical opportunities for the future.

  5. Innate protection from graft-versus-host disease

    NARCIS (Netherlands)

    T. Cupedo (Tom)

    2014-01-01

    textabstractIn this issue of Blood, Hazenberg and Spits provide a detailed overview of human innate lymphoid cell (ILC) subsets and their development and distribution throughout the human body, discussing these cells in the context of human disease. In the same issue, Munneke et al for the first tim

  6. IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE

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    G. A. Efimov

    2015-01-01

    Full Text Available Transplantation of allogeneic hematopoietic stem cells is the only curative option for a number of diseases of hematopoietic system. It is intended to replace the hematopoietic system of the recipient withthe donor’s. However, when mature T cells contained in the graft enter the recipient organism, it may lead to a severe post-transplant complication, the “graft versus host” disease (GVHD. It occurs due to the fact that the donor immune system contains T cell clones specific to recipient alloantigens. These cell clones are activated upon encountering their antigens, thus causing systemic damage to healthy tissues. Development of the alloreactive clones is caused by genetic differences between donor and recipient. The most importantfactors determining successful transplantation concern the compatibility for the genes coding for Major Histocompatibility Complex (MHC, that are expressed in all nucleated cells and are responsible for antigen presentation to the immune cells. Currently established extensive donor banks allow for majority of patients to choose a compatible donor. However, this does not provide complete prevention of the GVHD development, because in addition to the MHC genes the donor and recipient may differ in so-called minor histocompatibility antigens. Minor antigens may be caused by genetic polymorphisms in all of the genome coding regions. Pre-transplantation conditioning of the patient, which is necessary for engraftment represent an additional factor contributing to the GVHDdevelopment, since as its side effect it leads to formation of a pro-inflammatory environment in the organism of recipient. Severe GVHD develops in approximately 40% of MHC-matched patients, while in cases of partial compatibility this proportion is even higher. GVHD causes mortality comparable to other causes of posttransplantdeath, such as viral infections or relapse of underlying disease. Thus, the development of severe GVHD is a

  7. Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

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    Amr Nassar

    2014-01-01

    Full Text Available Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m2 seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals.

  8. Immune Mechanisms of Mesenchymal Stem Cell Therapy for Acute Graft versus Host Disease

    OpenAIRE

    Tobin, Laura M.

    2012-01-01

    The aim of this work was to investigate the role of Mesenchymal stem cells (MSC) in the modulation of immune responses, focusing on suppression and induction of immune tolerance. To date, MSC therapy has proved beneficial for the treatment of inflammatory and autoimmune diseases, such as acute Graft versus Host Disease (aGvHD) and Crohn’s disease. However, the exact mechanisms of therapeutic benefit remain unclear. The key goals of this study were to identify the role of MSC derived soluble a...

  9. Pathophysiology, prevention, and treatment of acute graft-versus-host disease

    Directory of Open Access Journals (Sweden)

    Abhinav Deol

    2011-03-01

    Full Text Available Abhinav Deol, Voravit Ratanatharathorn, Joseph P UbertiDepartment of Oncology, Blood and Marrow Stem Cell Transplant Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USAAbstract: Acute graft-versus-host disease (aGVHD is an immunologically mediated inflammatory reaction, which continues to be a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplant. Although the occurrence and severity of this disease may be devastating, there is a proven immunologically mediated antitumor activity that accompanies the disease process, which has a beneficial effect on outcome. Animal models of graft-versus-host disease (GVHD have given us a conceptual model that has allowed a better understanding of the pathophysiology and offers a framework for understanding the complex interactions between antigen-presenting cells, donor T-cells, and cytokines in the development of aGVHD. It has also given us a model that allows testing of various strategies for prevention and treatment. New, innovative approaches for treatment and prevention of aGVHD including better donor selection with the use of sophisticated human leukocyte antigen typing, use of T-cell depletion, reduced-intensity transplant regimens, and improved pharmacologic immunosuppression have improved outcomes by decreasing the incidence and severity of aGVHD. However, the limitation of these strategies is that effective treatment and prevention of aGVHD is often accompanied by a concomitant rise in relapses, graft failure and infections, and ultimately no improvement in overall survival. Investigators are working on understanding the difference between GVHD and graft versus tumor effect, as this would be the key in improving outcomes for our patients. In this review, we will discuss the pathophysiology of aGVHD along with the preventative and treatment strategies.Keywords: acute GVHD, GVHD, acute graft-versus-host

  10. Pharmacologic prophylaxis regimens for acute graft-versus-host disease: past, present and future.

    Science.gov (United States)

    Ram, Ron; Storb, Rainer

    2013-08-01

    Abstract Acute graft-versus-host disease (GVHD) has compromised and continues to compromise the benefits associated with allogeneic hematopoietic cell transplant to cure malignant and non-malignant diseases. Pharmacologic interventions to prevent GVHD have emerged as a major objective of research in the immunology and transplant fields. A better understanding of the pathobiology behind the GVHD process has led the way to novel approaches and medications. Here we review the present arsenal of medications used to prevent GVHD, focusing on past experience and the current evidence, and discuss future potential targets. PMID:23278640

  11. The Impact of HLA-E Polymorphisms in Graft-versus-Host Disease following HLA-E Matched Allogeneic Hematopoietic Stem Cell Transplantation

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    Ehteramolsadat Hosseini

    2012-03-01

    Full Text Available The  non-classical MHC  class-I mainly involves in the  regulation of  innate  immune responses where HLA-E  plays a significant role in the cell identification by natural killer cells. HLA-E is a main regulatory ligand for natural killer cells and given the importance of these effector cells in hematopoietic stem cell transplantation, we investigated the effect of HLA-E polymorphisms on post-hematopoietic stem cell transplantation outcomes.The study group included 56 donor-patient pairs with underlying malignant hematological disorders undergoing HLA-E  matched allogeneic hematopoietic stem cell transplantation. They were genotyped for HLA-E locus using a sequence specific primer-polymerase chain reaction. The  median follow-up was 20.6 months  (range 0.2-114.8 and  the  parameters assessed were acute and chronic graft-versus-host disease and overall survival.We showed a lower frequency of acute graft-versus-host disease (grade II or more; p=0.02and chronic graft-versus-host disease (extensive; p=0.04 in the patients with HLA- E*0103/0103 genotype compared to other genotypes of HLA-E. There was also an association between HLA-E*0103/0103 and improved overall survival (p=0.001.Conclusively, our  results  suggest a  protective  role  for  HLA-E*0103/0103  genotypeagainst acute graft-versus-host disease (grade II or more and chronic graft-versus-host disease (extensive as well as an association between this genotype and a better overall survival after HLA-E matched allogeneic hematopoietic stem cell transplantation.

  12. Chronic cutaneous graft-versus-host disease: a case report and literature review%皮肤慢性移植物抗宿主病1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    熊晓刚; 刘业强; 徐晓; 刘波; 雷晴; 卢军; 余泽莹; 陈方元; 涂圣安

    2012-01-01

    报告1例皮肤慢性移植物抗宿主病.患者男,25岁.全身泛发性皮损5年,主要表现为全身弥漫性色素减退伴色素加深的苔藓样斑片.面部呈现激素依赖性皮炎样表现.毛发稀疏,眉毛和腋毛脱落,睫毛及阴毛发白.手(足)指(趾)甲失去光泽,表面有纵嵴,部分缺损、萎缩.臀部皮损组织病理检查表现为苔藓样浸润模式.诊断:皮肤慢性移植物抗宿主病.给予糖皮质激素及他克莫司系统治疗,皮损改善不明显.%A 25-year-old man presented with a 5-year history of hyperpigmented and hypopigmented lichenoid skin lesions all over the body. There was steroid-dependent dermatitis-like manifestation on the face. Hair loss was evident on the scalp, eyebrows, armpit. Eyelashes and pubic hairs were white. Nail changes included brittleness, roughness, longitudinal ridges, and onychomadesis and onychatrophia. Histopathology of skin lesions on the buttocks revealed a pattern of lichenoid infiltration. The diagnosis was made as chronic cutaneous Graft-versus-host disease. The patient received daily oral corticosteroids in combination with systemic tacrolimus. No improvement had been obtained.

  13. National Institutes of Health classification for chronic graft-versus-host disease predicts outcome of allo-hematopoietic stem cell transplant after fludarabine-busulfan-antithymocyte globulin conditioning regimen.

    Science.gov (United States)

    Saillard, Colombe; Crocchiolo, Roberto; Furst, Sabine; El-Cheikh, Jean; Castagna, Luca; Signori, Alessio; Oudin, Claire; Faucher, Catherine; Lemarie, Claude; Chabannon, Christian; Granata, Angela; Blaise, Didier

    2014-05-01

    Abstract In 2005, the National Institutes of Health (NIH) proposed standard criteria for diagnosis, organ scoring and global assessment of chronic graft-versus-host disease (cGvHD) severity. We retrospectively reclassified cGvHD with NIH criteria in a monocentric cohort of 130 consecutive adult patients with hematological malignancies presenting cGvHD after receiving allo-hematopoietic stem cell transplant (HSCT) with a fludarabine-busulfan-antithymocyte globulin (ATG) conditioning regimen, among 313 consecutive HSCT recipients. We compared NIH and Seattle classifications to correlate severity and outcome. The follow up range was effectively 2-120 months. Forty-four percent developed Seattle-defined cGvHD (22% limited, 78% extensive forms). Using NIH criteria, there were 23%, 40% and 37% mild, moderate and severe forms, respectively, and 58%, 32% and 8% classic cGvHD, late acute GvHD and overlap syndrome. Five-year overall survival was 55% (49-61), and cumulative incidences of non-relapse mortality (NRM) and relapse/progression at 2 years were 19% (14-23) and 19% (14-24). NIH mild and moderate forms were associated with better survival compared to severe cGvHD (hazard ratio [HR] = 3.28, 95% confidence interval [CI]: 1.38-7.82, p = 0.007), due to higher NRM among patients with severe cGvHD (HR = 3.04, 95% CI: 1.05-8.78, p = 0.04) but comparable relapse risk (p = NS). In conclusion, the NIH classification appears to be more accurate in predicting outcome mostly by the reclassification of old-defined extensive forms into NIH-defined moderate or severe.

  14. Donor Requirements for Regulatory T Cell Suppression of Murine Graft Versus Host Disease

    OpenAIRE

    Pierini, Antonio; Colonna, Lucrezia; Alvarez, Maite; Schneidawind, Dominik; Nishikii, Hidekazu; Baker, Jeanette; Pan, Yuqiong; Florek, Mareike; Kim, Byung-Su; Negrin, Robert S.

    2015-01-01

    Adoptive transfer of freshly isolated natural occurring CD4+CD25+FoxP3+ regulatory T cells (Treg) prevents graft versus host disease (GvHD) in several animal models and following hematopoietic cell transplantation (HCT) in clinical trials. Donor derived Treg have been mainly used as they share the same MHC with conventional CD4+ and CD8+ T cells (Tcon) that are primarily responsible for GvHD. Third-party derived Treg are a promising alternative for cellular therapy as they can be prepared in ...

  15. Humanized Chronic Graft-versus-Host Disease in NOD-SCID il2rγ-/- (NSG Mice with G-CSF-Mobilized Peripheral Blood Mononuclear Cells following Cyclophosphamide and Total Body Irradiation.

    Directory of Open Access Journals (Sweden)

    Hisaki Fujii

    Full Text Available Chronic graft-versus-host disease (cGvHD is the major source of late phase morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Humanized acute GvHD (aGvHD in vivo models using NOD-SCID il2rγ-/- (NSG mice are well described and are important tools for investigating pathogenicity of human cells in vivo. However, there have been only few reported humanized cGvHD mouse models. We evaluated if prolonged inflammation driven by low dose G-CSF-mobilized human PBMCs (G-hPBMCs would lead to cGvHD following cyclophosphamide (CTX administration and total body irradiation (TBI in NSG mice. Engraftment was assessed in peripheral blood (PB and in specific target organs by either flow cytometry or immunohistochemistry (IHC. Tissue samples were harvested 56 days post transplantation and were evaluated by a pathologist. Some mice were kept for up to 84 days to evaluate the degree of fibrosis. Mice that received CTX at 20mg/kg did not show aGvHD with stable expansion of human CD45+ CD3+ T-cells in PB (mean; 5.8 to 23.2%. The pathology and fibrosis scores in the lung and the liver were significantly increased with aggregation of T-cells and hCD68+ macrophages. There was a correlation between liver pathology score and the percentage of hCD68+ cells, suggesting the role of macrophage in fibrogenesis in NSG mice. In order to study long-term survival, 6/9 mice who survived more than 56 days showed increased fibrosis in the lung and liver at the endpoint, which suggests the infiltrating hCD68+ macrophages may be pathogenic. It was shown that the combination of CTX and TBI with a low number of G-hPBMCs (1x106 leads to chronic lung and liver inflammation driven by a high infiltration of human macrophage and mature human T cells from the graft, resulting in fibrosis of lung and liver in NSG mice. In conclusion this model may serve as an important pre-clinical model to further current understanding of the roles of human macrophages in cGvHD.

  16. Humanized Chronic Graft-versus-Host Disease in NOD-SCID il2rγ-/- (NSG) Mice with G-CSF-Mobilized Peripheral Blood Mononuclear Cells following Cyclophosphamide and Total Body Irradiation.

    Science.gov (United States)

    Fujii, Hisaki; Luo, Zhi-Juan; Kim, Hye Jin; Newbigging, Susan; Gassas, Adam; Keating, Armand; Egeler, R Maarten

    2015-01-01

    Chronic graft-versus-host disease (cGvHD) is the major source of late phase morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Humanized acute GvHD (aGvHD) in vivo models using NOD-SCID il2rγ-/- (NSG) mice are well described and are important tools for investigating pathogenicity of human cells in vivo. However, there have been only few reported humanized cGvHD mouse models. We evaluated if prolonged inflammation driven by low dose G-CSF-mobilized human PBMCs (G-hPBMCs) would lead to cGvHD following cyclophosphamide (CTX) administration and total body irradiation (TBI) in NSG mice. Engraftment was assessed in peripheral blood (PB) and in specific target organs by either flow cytometry or immunohistochemistry (IHC). Tissue samples were harvested 56 days post transplantation and were evaluated by a pathologist. Some mice were kept for up to 84 days to evaluate the degree of fibrosis. Mice that received CTX at 20mg/kg did not show aGvHD with stable expansion of human CD45+ CD3+ T-cells in PB (mean; 5.8 to 23.2%). The pathology and fibrosis scores in the lung and the liver were significantly increased with aggregation of T-cells and hCD68+ macrophages. There was a correlation between liver pathology score and the percentage of hCD68+ cells, suggesting the role of macrophage in fibrogenesis in NSG mice. In order to study long-term survival, 6/9 mice who survived more than 56 days showed increased fibrosis in the lung and liver at the endpoint, which suggests the infiltrating hCD68+ macrophages may be pathogenic. It was shown that the combination of CTX and TBI with a low number of G-hPBMCs (1x106) leads to chronic lung and liver inflammation driven by a high infiltration of human macrophage and mature human T cells from the graft, resulting in fibrosis of lung and liver in NSG mice. In conclusion this model may serve as an important pre-clinical model to further current understanding of the roles of human macrophages in cGvHD.

  17. Successful treatment for graft-versus-host disease after pancreas transplantation.

    Science.gov (United States)

    Chang, Jei wen; Sageshima, Junichiro; Ciancio, Gaetano; Mattiazzi, Adela; Chen, Linda; Tsai, Hsin-Lin; Ruiz, Phillip; Burke, George W

    2014-02-01

    Graft-versus-host disease (GVHD) after pancreas transplantation is a rare but serious complication: All previously reported cases were fatal. We herein report three cases of GVHD after pancreas transplantation with favorable outcomes. Patients with a history of kidney (and pancreas) transplantation subsequently received a pancreas (and kidney) transplantation (i.e., pancreas retransplantation or pancreas after kidney transplantation) and developed acute GVHD. All of them responded to increased immunosuppression (e.g., steroid bolus, antithymocyte globulin) and retained normal graft function. Because the clinical manifestations are non-specific, vigilance is necessary to make an accurate diagnosis. We underscored the importance of a biopsy of involved organs and the clinicopathologic correlation in the early diagnosis of GVHD. Augmented immunosuppression to prevent progression from a self-limited disease to life-threatening pancytopenia or sepsis may be most critical to improve outcome.

  18. The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease

    Directory of Open Access Journals (Sweden)

    Yuanyuan Chen

    2015-01-01

    Full Text Available The mammalian intestinal microbiota is a complex ecosystem that plays an important role in host immune responses. Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to multiple inflammatory diseases in humans, including acute graft-versus-host disease (aGVHD. aGVHD is one of the major obstacles in allogeneic hematopoietic stem cell transplantation (allo-HSCT, characterized by tissue damage in the gastrointestinal (GI tract, liver, lung, and skin. Here, we review the current understanding of the role of intestinal microbiota in the control of immune responses during aGVHD. Additionally, the possibility of using probiotic strains for potential treatment or prevention of aGVHD will be discussed.

  19. Clinical Application of Mesenchymal Stem Cells in the Treatment and Prevention of Graft-versus-Host Disease

    Directory of Open Access Journals (Sweden)

    Yi Lin

    2011-01-01

    Full Text Available Mesenchymal stem cells (MSCs represent a heterogeneous population of stromal cells with pluripotent mesenchymal differentiation potential. They have been found to have immunosuppressive properties and the ability to modulate angiogenesis and endogenous tissue repair by in vitro and animal studies. Clinical trials have examined the utility of these cells in autoimmune and inflammatory conditions. In particular, in allogeneic hematopoietic stem cell transplant (HSCT, multiple studies have been conducted to explore the use of MSC to treat acute and chronic graft-versus-host disease (GVHD and for cotransplantation with HSCT to promote HSC engraftment and prevent GVHD. We review here the results of these studies and discuss some challenges of this treatment modality in this disease setting.

  20. Membranous nephropathy in autologous hematopoietic stem cell transplant: autologous graft-versus-host disease or autoimmunity induction?

    Science.gov (United States)

    Abudayyeh, Ala; Truong, Luan D.; Beck, Laurence H.; Weber, Donna M.; Rezvani, Katy; Abdelrahim, Maen

    2015-01-01

    With the increasing utility of hematopoietic stem cell transplantation (SCT) as a treatment for cancer and noncancerous disorders, more challenges and complications associated with SCT have emerged. Renal injury immediately after transplant is common and well understood, but long-term renal injury is becoming more evident. Chronic graft-versus-host disease (GVHD) is a known long-term complication of SCT, and membranous nephropathy (MN) is emerging as the most common cause of SCT-associated glomerular pathology. In this case report, we present a patient who developed features of anti-PLA2R antibody-negative MN following autologous SCT. The renal injury responded well to steroids and further response to rituximab therapy was noted, suggesting antibody-mediated autoimmune glomerular disease. We also present a review of the literature on autologous GVHD and the role of T and B cells in induction of autoimmunity by SCT. PMID:26251713

  1. T-Cell Costimulatory Molecules in Acute-Graft-Versus Host Disease: Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Javier Briones

    2011-01-01

    Full Text Available Acute Graft-versus-host disease (GVHD is a major complication after allogeneic hematopoietic stem cell transplantation. Although this process is thought to consist of several phases, T-cell activation plays a critical role in the pathogenesis of acute GVHD. To become efficient effectors, T-cells require additional costimulation after T-cell receptor signaling. A number of molecules are involved in costimulation of T-cells such as CD28, CD40L, CD30, OX40, 4-1BB, ICOS, and LIGHT. The system is regulated by inhibitory molecules, CTLA-4, and PD-1. There is experimental evidence that those molecules are implicated in the pathogenesis of GHVD. We describe how these molecules are involved in acute GVHD and how the blockade of costimulatory molecules may have potential implications for the treatment of patients with acute GVHD.

  2. Enlargement of the human spleen in graft-versus-host disease.

    Science.gov (United States)

    Dilly, S A; Sloane, J P

    1988-04-01

    The spleens of 49 patients who had undergone allogeneic bone marrow transplantation for leukemia were compared at autopsy to determine the pathological changes associated with graft-versus-host disease (GVHD). The only significant finding was an increase in weight of about 1.7 times that of spleens from patients without GVHD. This was not explained by differences in the patients' sex, length of survival after transplantation, presence of infection, or liver pathology. On histological examination, there was no detectable increase in congestion, siderosis, or numbers of lymphocytes, macrophages, antigen-presenting cells, blast cells, pyknotic cells, plasma cells, or hemopoietic cells to explain the increase in spleen weight. On the contrary, there was actually a reduction in CD8+ T lymphocytes. No proliferative phase of GVHD could be identified, possibly due to a lack of specimens examined less than 8 days after transplantation and to prophylactic measures undertaken to minimize GVHD. The pathogenesis of splenomegaly in human GVHD is unclear.

  3. New Insight for the Diagnosis of Gastrointestinal Acute Graft-versus-Host Disease

    Directory of Open Access Journals (Sweden)

    Florent Malard

    2014-01-01

    Full Text Available Allogeneic stem cell transplantation (allo-SCT is a curative therapy for different life-threatening malignant and nonmalignant hematologic disorders. Graft-versus-host disease (GVHD remains a major source of morbidity and mortality following allo-SCT, which limits the use of this treatment in a broader spectrum of patients. Early diagnostic of GVHD is essential to initiate treatment as soon as possible. Unfortunately, the diagnosis of GVHD may be difficult to establish, because of the nonspecific nature of the associated symptoms and of the numerous differential diagnosis. This is particularly true regarding gastrointestinal (GI acute GVHD. In the recent years many progress has been made in medical imaging test and endoscopic techniques. The interest of these different techniques in the diagnosis of GI acute GVHD has been evaluated in several studies. With this background we review the contributions, limitations, and future prospect of these techniques in the diagnosis of GI acute GVHD.

  4. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Baron, F; Labopin, M; Niederwieser, D;

    2012-01-01

    This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of rela...

  5. Economic evaluation of posaconazole versus fluconazole prophylaxis in patients with graft-versus-host disease (GVHD) in the Netherlands

    NARCIS (Netherlands)

    J.P. Jansen (Jeroen); A.K. O'Sullivan (Amy); P.J. Lugtenburg (Pieternella); L.F.R. Span (Lambert); J.J.W.M. Janssen (Jeroen); W.B. Stam (Wiro)

    2010-01-01

    textabstractThe objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind ra

  6. Economic evaluation of posaconazole versus fluconazole prophylaxis in patients with graft-versus-host disease (GVHD) in the Netherlands

    NARCIS (Netherlands)

    Jansen, Jeroen P.; O'Sullivan, Amy K.; Lugtenburg, Elly; Span, Lambert F. R.; Janssen, Jeroen J. W. M.; Stam, Wiro B.

    2010-01-01

    The objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind randomized tri

  7. A case of graft-versus-host disease following irradiated fresh blood transfusion

    International Nuclear Information System (INIS)

    We reported a case of a fatal graft-versus-host disease (GVHD) which developed in a 65-year-old, male patient which was considered to have been induced by irradiated fresh blood donated by his son after a coronary bypass surgery. Fresh blood was obtained from his relatives, and a 15 Gy irradiation was performed before transfusion. The diagnosis of acute GVHD was made by clinical symptoms and histological examinations of the skin and the bone marrow. He died of sepsis on the 19th post-operative day. The HLA typing of the lymphocytes, revealed that the patient had A 2, A 24, Bw 52, Bw 62, Cw 4, DR 2, and his son had A 24, Bw 52, DR 2. A 24 and Bw 52 were homogeneous making his son histocompatible with one of the patient's haplotype. This might well be attributable to the occurrence of GVHD in this case, meaning that 15 Gy irradiation was not sufficient for the prevention of this disease. (author)

  8. Skin and kidney histological changes in graft-versus-host disease (GVHD) after kidney transplantation.

    Science.gov (United States)

    Pintar, Tadeja; Alessiani, Mario; Pleskovič, Alojz; Pleskovič, Aleš; Zorc-Pleskovič, Ruda; Milutinović, Aleksandra

    2011-05-01

    Kidney transplantation (Ktx) is generally performed during end stage renal disease due to a loss of the kidneys' ability to filter wastes from the circulatory system. Acute graft-versus-host disease (GVHD) after Ktx is a life-threatening complication that progresses to organ failure, systemic complications, and death. The current study evaluated the significance of histologic findings of GVHD as obtained from skin biopsies following Ktx in swine. A swine model of Ktx with tacrolimus-based immunosuppression was used to assess possible correlations between acute-graft-cellular rejection and skin histological findings for prediction of GVHD. Animals were divided into a Ktx treatment group or a control group with no Ktx and skin and kidney biopsies were histologically assessed at postoperative days 0, 15, 30, 45 and 60. Skin samples were analyzed and classified from grade 1 to 4 of skin GVHD and the major histopathological changes of kidney acute cellular rejection were described using Banff's score system. We observed a significant linear correlation between the histological grading values of skin biopsy changes and the histological grading values of kidney biopsies (Kendall's tau_b=0.993) in the Ktx experimental group. No histological changes were observed in controls. Our findings demonstrate the diagnostic value of staging skin GVHD after Ktx and suggest it's future utility for monitoring long term Ktx-induced changes.

  9. Memory CD4+ T cells do not induce graft-versus-host disease.

    Science.gov (United States)

    Anderson, Britt E; McNiff, Jennifer; Yan, Jun; Doyle, Hester; Mamula, Mark; Shlomchik, Mark J; Shlomchik, Warren D

    2003-07-01

    Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany stem cell grafts cause GVHD by attacking recipient tissues; therefore, all patients receive GVHD prophylaxis by depletion of T cells from the allograft or through immunosuppressant drugs. In addition to providing a graft-versus-leukemia effect, donor T cells are critical for reconstituting T cell-mediated immunity. Ideally, immunity to infectious agents would be transferred from donor to host without GVHD. Most donors have been exposed to common pathogens and have an increased precursor frequency of memory T cells against pathogenic antigens. We therefore asked whether memory CD62L-CD44+ CD4+ T cells would induce less GVHD than unfractionated or naive CD4+ T cells. Strikingly, we found that memory CD4 cells induced neither clinical nor histologic GVHD. This effect was not due to the increased number of CD4+CD25+ regulatory T cells found in the CD62L-CD44+ fraction because memory T cells depletion of these cells did not cause GVHD. Memory CD4 cells engrafted and responded to antigen both in vivo and in vitro. If these murine results are applicable to human alloSCT, selective administration of memory T cells could greatly improve post-transplant immune reconstitution.

  10. Danger signals activating innate immunity in graft-versus-host disease.

    Science.gov (United States)

    Zeiser, Robert; Penack, Olaf; Holler, Ernst; Idzko, Marco

    2011-09-01

    Extensive cell death with consecutive release of danger signals can cause immune-mediated tissue destruction. The abundance of cell death is likely to determine the relevance of the danger signals as physiological mechanisms that counteract immune activation may be overruled. Such constellation is conceivable in chemo-/radiotherapy-induced tissue damage, reperfusion injury, trauma, and severe infection. Studies on graft-versus-host disease (GvHD) development have to consider the effects of chemo-/radiotherapy-related tissue damage leading to the release of exogenous and endogenous danger signals. Our previous work has demonstrated a role for adenosine-5'-triphosphate (ATP) as an endogenous danger signal in GvHD. Besides ATP, uric acid or soluble extracellular matrix components are functional danger signals that activate the NLRP3 inflammasome when released from dying cells or from extracellular matrix. In contrast to sterile inflammation, GvHD is more complex since bacterial components that leak through damaged intestinal barriers and the skin can activate pattern recognition receptors and directly contribute to GvHD pathogenesis. These exogenous danger signals transmit immune activation via toll-like receptors and NOD-like receptors of the innate immune system. This review covers both the impact of endogenous and exogenous danger signals activating innate immunity in GvHD.

  11. Defecation of a colon cast as a rare presentation of acute graft-versus-host disease

    International Nuclear Information System (INIS)

    Diffuse involvement of the gastrointestinal tract by graft versus host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplant (HSCT). Gastrointestinal GVHD usually presents 3 or more weeks after HSCT and is characterized by profuse diarrhea, anorexia, nausea, vomiting, abdominal pain and gastrointestinal bleeding. We report a case of a 23 year old male who had undergone allogeneic HSCT and presented with bloody diarrhea on the 90th day post-HSCT. On the fourth day of admission, the patient passed per rectum a 27-cm long pinkish colored fleshy material recognized as a colon cast. Sigmoidoscopy showed a congested and erythematous rectum with the remaining portion of the colon cast attached to the proximal part of the sigmoid colon. A biopsy from the rectal wall was suggestive of grade 4 GVHD. The patient was treated with methylprednisolone, cyclosporine and mycophenolate mofetil, with a partial response (diarrhea and abdominal pain improved), but then he developed multiple other medical complications and died after 3 months. (author)

  12. Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease.

    Science.gov (United States)

    Jenq, Robert R; Taur, Ying; Devlin, Sean M; Ponce, Doris M; Goldberg, Jenna D; Ahr, Katya F; Littmann, Eric R; Ling, Lilan; Gobourne, Asia C; Miller, Liza C; Docampo, Melissa D; Peled, Jonathan U; Arpaia, Nicholas; Cross, Justin R; Peets, Tatanisha K; Lumish, Melissa A; Shono, Yusuke; Dudakov, Jarrod A; Poeck, Hendrik; Hanash, Alan M; Barker, Juliet N; Perales, Miguel-Angel; Giralt, Sergio A; Pamer, Eric G; van den Brink, Marcel R M

    2015-08-01

    The relationship between intestinal microbiota composition and acute graft-versus-host disease (GVHD) after allogeneic blood/marrow transplantation (allo-BMT) is not well understood. Intestinal bacteria have long been thought to contribute to GVHD pathophysiology, but recent animal studies in nontransplant settings have found that anti-inflammatory effects are mediated by certain subpopulations of intestinal commensals. Hypothesizing that a more nuanced relationship may exist between the intestinal bacteria and GVHD, we evaluated the fecal bacterial composition of 64 patients 12 days after BMT. We found that increased bacterial diversity was associated with reduced GVHD-related mortality. Furthermore, harboring increased amounts of bacteria belonging to the genus Blautia was associated with reduced GVHD lethality in this cohort and was confirmed in another independent cohort of 51 patients from the same institution. Blautia abundance was also associated with improved overall survival. We evaluated the abundance of Blautia with respect to clinical factors and found that loss of Blautia was associated with treatment with antibiotics that inhibit anaerobic bacteria and receiving total parenteral nutrition for longer durations. We conclude that increased abundance of commensal bacteria belonging to the Blautia genus is associated with reduced lethal GVHD and improved overall survival.

  13. Lethal graft-versus-host disease: modification with allogeneic cultured donor cells

    International Nuclear Information System (INIS)

    The use of the bone marrow culture technique was studied as a means to prepare donor marrow for bone marrow transplantation to avoid lethal graft-versus-host disease (GVHD). Preliminary experiments demonstrated the rapid loss of theta-positive cells in such cultures, so that theta-positive cells were not detected after 6 days. Initial experiments in C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in place of hind limb marrow for transplantation. However, hemoglobin typing of recipient animals revealed only short-term donor engraftment, with competitive repopulation of recipient marrow occurring. Subsequent experiments were done in 1,200-rad prepared recipients, with long-term donor engraftment demonstrated. The majority of 1,200-rad prepared animals receiving cultured allogeneic cells died of GVHD, but animals receiving 28-day cultured cells had an improved 90-day survival and a delay in GVHD development over animals receiving hind limb marrow or marrow from shorter times in culture. In addition, animals receiving anti-theta-treated, 3-day nonadherent cells had an improved survival (44%) over animals receiving anti-theta-treated hind limb marrow (20%). These experiments demonstrate modest benefit for the use of cultured cells in bone marrow transplantation across major H-2 histocompatibility complex differences

  14. Improved accuracy of acute graft-versus-host disease staging among multiple centers.

    Science.gov (United States)

    Levine, John E; Hogan, William J; Harris, Andrew C; Litzow, Mark R; Efebera, Yvonne A; Devine, Steven M; Reshef, Ran; Ferrara, James L M

    2014-01-01

    The clinical staging of acute graft-versus-host disease (GVHD) varies significantly among bone marrow transplant (BMT) centers, but adherence to long-standing practices poses formidable barriers to standardization among centers. We have analyzed the sources of variability and developed a web-based remote data entry system that can be used by multiple centers simultaneously and that standardizes data collection in key areas. This user-friendly, intuitive interface resembles an online shopping site and eliminates error-prone entry of free text with drop-down menus and pop-up detailed guidance available at the point of data entry. Standardized documentation of symptoms and therapeutic response reduces errors in grade assignment and allows creation of confidence levels regarding the diagnosis. Early review and adjudication of borderline cases improves consistency of grading and further enhances consistency among centers. If this system achieves widespread use it may enhance the quality of data in multicenter trials to prevent and treat acute GVHD. PMID:25455279

  15. Endothelial-cell injury in cutaneous acute graft-versus-host disease.

    Science.gov (United States)

    Dumler, J. S.; Beschorner, W. E.; Farmer, E. R.; Di Gennaro, K. A.; Saral, R.; Santos, G. W.

    1989-01-01

    The presence of an erythematous skin rash and hemorrhagic complications in acute graft-versus-host disease (GVHD) suggest that the vasculature may be involved in the immunopathologic process. We reviewed endothelial and vascular histopathologic changes on light microscopy and on immunoperoxidase stained sections of skin biopsies obtained from 41 HLA-identical allogeneic marrow transplant recipients with at least grade 2 GVHD. Biopsies taken from 14 allogeneic HLA-identical bone marrow transplant recipients who never developed GVHD were used as controls. Sections were evaluated for evidence of immunologic vascular injury using the rank file analysis of histologic features, expression of HLA-DR antigen, and the distribution of fibrin and factor VIII-related antigen (F VIII RAg). Patients with acute GVHD had significantly greater intimal lymphocytic infiltrates, perivascular nuclear dust deposition, perivascular F VIII Rag extravasation and deposition and vascular proliferation than controls. We find significantly greater endothelial injury in GVHD patients, which may represent primary immunologic injury to the vasculature. The clinical findings in acute GVHD probably result from cumulative endothelial as well as epithelial injury. Images Figure 1 Figure 2 Figure 3 PMID:2596572

  16. The Role of Purine Metabolites as DAMPs in Acute Graft-versus-Host Disease

    Science.gov (United States)

    Apostolova, Petya; Zeiser, Robert

    2016-01-01

    Acute graft-versus-host disease (GvHD) causes high mortality in patients undergoing allogeneic hematopoietic cell transplantation. An early event in the classical pathogenesis of acute GvHD is tissue damage caused by the conditioning treatment or infection that consecutively leads to translocation of bacterial products [pathogen-associated molecular patterns (PAMPs)] into blood or lymphoid tissue, as well as danger-associated molecular patterns (DAMPs), mostly intracellular components that act as pro-inflammatory agents, once they are released into the extracellular space. A subtype of DAMPs is nucleotides, such as adenosine triphosphate released from dying cells that can activate the innate and adaptive immune system by binding to purinergic receptors. Binding to certain purinergic receptors leads to a pro-inflammatory microenvironment and promotes allogeneic T cell priming. After priming, T cells migrate to the acute GvHD target organs, mainly skin, liver, and the gastrointestinal tract and induce cell damage that further amplifies the release of intracellular components. This review summarizes the role of different purinergic receptors in particular P2X7 and P2Y2 as well as nucleotides in the pathogenesis of GvHD.

  17. Graft-Versus-Host Disease after Liver Transplantation Complicated by Systemic Aspergillosis with Pancarditis

    Directory of Open Access Journals (Sweden)

    Joseph Romagnuolo

    2000-01-01

    Full Text Available Acute graft-versus-host disease (GVHD is a common complication after bone marrow transplantation, with characteristic rash and diarrhea being the most common features. After liver transplantation, however, this phenomenon is very rare. Most transplant patients are on a variety of medications, including immunosuppressants; therefore, the differential diagnosis of skin rash or diarrhea is broad. A 37-year-old man who underwent liver transplantation for primary biliary cirrhosis, and developed a rash and watery diarrhea, is presented. Skin and colonic biopsies confirmed acute GVHD. A pulse of intravenous steroids was given. The skin rash improved, but he developed pancytopenia. His course was complicated by central line infection, jugular and subclavian vein thrombosis, pseudomembranous colitis, recurrent bacteremia, cholestasis on total parenteral nutrition and cytomegalovirus infection. After the onset of pleuritic chest pain and clinical sepsis, spiral computed tomography scan of his chest and abdomen revealed septic infarcts in multiple organs. Despite empirical treatment with amphotericin B, he died of multiorgan dysfunction syndrome within 72 h. Autopsy revealed systemic aspergillosis with pancarditis, endocardial vegetations, and septic pulmonary, splenic, hepatic and renal infarcts. The pathogenesis and experience with this rare, but often fatal, complication of liver transplantation are reviewed. In contrast to GVHD after bone marrow transplantation, pancytopenia is common and liver dysfunction is rare. One should have a high level of suspicion in the liver transplant recipient presenting with rash and/or diarrhea.

  18. Ocular Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation: A Review of Current Knowledge and Recommendations

    OpenAIRE

    Nariman Nassiri; Medi Eslani; Nekoo Panahi; Shiva Mehravaran; Alireza Ziaei; Djalilian, Ali R.

    2013-01-01

    Graft versus host disease (GVHD) is a common complication of allogeneic stem cell transplantation (allo-SCT). Ocular GVHD develops in approximately 40-60% of patients following allo-SCT and its most common clinical manifestations include keratoconjunctivitis sicca and cicatricial conjunctivitis. Ocular GVHD may lead to severe ocular surface disease, which can significantly diminish quality of life and restrict daily activities. It is thus important to monitor the condition closely since with ...

  19. Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    Lorenz, Fryderyk; Marklund, Stefan; Werner, Mårten; Palmqvist, Richard; Wahlin, Bjorn Engelbrekt; Wahlin, Anders

    2015-01-01

    The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The ...

  20. Anaplerotic Metabolism of Alloreactive T Cells Provides a Metabolic Approach To Treat Graft-Versus-Host Disease

    OpenAIRE

    Glick, Gary D.; Rossignol, Rodrigue; Lyssiotis, Costas A.; Wahl, Daniel; Lesch, Charles; Sanchez, Brian; Liu, Xikui; Hao, Ling-Yang; Taylor, Clarke; Hurd, Alexander; Ferrara, James L. M.; Tkachev, Victor; Byersdorfer, Craig A.; Boros, Laszlo; Opipari, Anthony W.

    2014-01-01

    T-cell activation requires increased ATP and biosynthesis to support proliferation and effector function. Most models of T-cell activation are based on in vitro culture systems and posit that aerobic glycolysis is employed to meet increased energetic and biosynthetic demands. By contrast, T cells activated in vivo by alloantigens in graft-versus-host disease (GVHD) increase mitochondrial oxygen consumption, fatty acid uptake, and oxidation, with small increases of glucose uptake and aerobic g...

  1. Autologous Graft versus Host Disease: An Emerging Complication in Patients with Multiple Myeloma

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    Anu Batra

    2014-01-01

    Full Text Available Autologous graft versus host disease (autoGVHD is a rare transplant complication with significant morbidity and mortality. It has been hypothesized that patients with multiple myeloma might be predisposed to autoGVHD through dysregulation of the immune response resulting from either their disease, the immunomodulatory agents (IMiDs used to treat it, or transplant conditioning regimen. Hematopoietic progenitor cell (HPC products were available from 8 multiple myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma patients who did not develop autoGVHD, and 7 healthy research donors. The data on number of transplants prior to developing autoGVHD, mobilization regimens, exposure to proteasome inhibitors, use of IMiDs, and class I human leukocyte antigen types (HLA A and B were collected. The HPC products were analyzed by flow cytometry for expression of CD3, CD4, CD8, CD25, CD56, and FoxP3. CD3+ cell number was significantly lower in autoGVHD patients compared to unaffected controls (P=0.047. On subset analysis of CD3+ cells, CD8+ cells (but not CD4+ cells were found to be significantly lower in patients with autoGVHD (P=0.038. HLA-B55 expression was significantly associated with development of autoGVHD (P=0.032. Lower percentages of CD3+ and CD8+ T-cells and HLA-B55 expression may be predisposing factors for developing autoGVHD in myeloma.

  2. IL-35 inhibits acute graft-versus-host disease in a mouse model.

    Science.gov (United States)

    Zhang, Xiao-Hui; Zhou, Yi; Zhang, Jia-Min; Zhou, Shi-Yuan; Wang, Min; Feng, Ru; Feng, Fer-Er; Wang, Qian-Ming; Zhu, Xiao-Lu; Zhao, Xiao-Su; Lv, Meng; Kong, Yuan; Chang, Ying-Jun; Huang, Xiao-Jun

    2015-12-01

    Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our previous study found that the novel anti-inflammatory cytokine IL-35 could suppress aGVHD in patients after allo-HSCT. In this study, we used C57BL/6 (B6, H-2b) mice as donors and (B6×DBA/2) F1 (BDF1, H-2b×d) mice as recipients to create a model of aGVHD and explore the relationship between IL-35 and aGVHD. The mice receiving IL-35 survived longer than did the control mice. We observed that treatment with IL-35 and RAPA could reduce the incidence of aGVHD. Additionally, this treatment inhibited intestinal and thymic epithelial cell apoptosis and liver infiltration by the donor T-cells, thereby ameliorating the enteropathy and liver injury caused by aGVHD. We found that IL-35 and RAPA also markedly suppressed TNF-α and IL-17A expression and enhanced IFN-γ expression in the intestine and liver. We measured Tregs in spleen and found that IL-35 and RAPA treatment expanded the number of Tregs in spleen. We found that the phosphorylation of STAT1 and STAT4 were inhibited in mice with aGVHD. In contrast, STAT1 and STAT4 were phosphorylated when the mice were treated with IL-35. IL-35 may have therapeutic potential in the treatment of aGVHD after allo-HSCT.

  3. Targeting the IL17 pathway for the prevention of graft-versus-host disease.

    Science.gov (United States)

    van der Waart, Anniek B; van der Velden, Walter J F M; Blijlevens, Nicole M; Dolstra, Harry

    2014-06-01

    Graft-versus-host disease (GVHD) is still a major complication of allogeneic stem cell transplantation (allo-SCT). The pathophysiology of GVHD is a multistep process initiated by tissue damage and proinflammatory cytokine cascades induced by the pretransplantation conditioning therapy. This eventually results in Th1-driven tissue damage. However, increasing evidence indicates the involvement of IL17-producing T cells in GVHD pathogenesis. Both CD4(+) and CD8(+) IL17-producing T cells are suspected of initiating the Th1 response and aggravating tissue inflammation, resulting in full-blown GVHD. In this review, we discuss the involvement of IL17-producing T cells in GVHD and the factors involved in their expansion, differentiation, and activation. Different dendritic cell (DC) subsets, such as plasmacytoid DCs and DC NK lectin group receptor 1(+) myeloid DCs have the capability to stimulate Th/Tc17 responses through the release of cytokines. Pivotal cytokines include IL1β, IL6, IL23, and TGFβ, which are known to drive differentiation and expansion of IL17-producing T cells, and these cytokines are highly elevated in patients after allo-SCT. Potent activators of these DC subsets are motifs that are released upon tissue damage and microbial exposure during allo-SCT. These motifs aggravate the Th/Tc17 response via the activation of various pathogen recognition receptors, thereby initiating and perpetuating GVHD. A more comprehensive understanding of the factors and DC subsets driving the IL17 pathway will result in developing and testing novel therapeutic approaches for the prevention of GVHD. PMID:24565991

  4. IL-35 inhibits acute graft-versus-host disease in a mouse model.

    Science.gov (United States)

    Zhang, Xiao-Hui; Zhou, Yi; Zhang, Jia-Min; Zhou, Shi-Yuan; Wang, Min; Feng, Ru; Feng, Fer-Er; Wang, Qian-Ming; Zhu, Xiao-Lu; Zhao, Xiao-Su; Lv, Meng; Kong, Yuan; Chang, Ying-Jun; Huang, Xiao-Jun

    2015-12-01

    Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our previous study found that the novel anti-inflammatory cytokine IL-35 could suppress aGVHD in patients after allo-HSCT. In this study, we used C57BL/6 (B6, H-2b) mice as donors and (B6×DBA/2) F1 (BDF1, H-2b×d) mice as recipients to create a model of aGVHD and explore the relationship between IL-35 and aGVHD. The mice receiving IL-35 survived longer than did the control mice. We observed that treatment with IL-35 and RAPA could reduce the incidence of aGVHD. Additionally, this treatment inhibited intestinal and thymic epithelial cell apoptosis and liver infiltration by the donor T-cells, thereby ameliorating the enteropathy and liver injury caused by aGVHD. We found that IL-35 and RAPA also markedly suppressed TNF-α and IL-17A expression and enhanced IFN-γ expression in the intestine and liver. We measured Tregs in spleen and found that IL-35 and RAPA treatment expanded the number of Tregs in spleen. We found that the phosphorylation of STAT1 and STAT4 were inhibited in mice with aGVHD. In contrast, STAT1 and STAT4 were phosphorylated when the mice were treated with IL-35. IL-35 may have therapeutic potential in the treatment of aGVHD after allo-HSCT. PMID:26507167

  5. Induction of Graft-versus-host Disease and In Vivo T Cell Monitoring Using an MHC-matched Murine Model

    OpenAIRE

    Anthony, Bryan A.; Hadley, Gregg A.

    2012-01-01

    Graft-versus-host disease (GVHD) is the limiting barrier to the broad use of bone marrow transplant as a curative therapy for a variety of hematological deficiencies. GVHD is caused by mature alloreactive T cells present in the bone marrow graft that are infused into the recipient and cause damage to host organs. However, in mice, T cells must be added to the bone marrow inoculum to cause GVHD. Although extensive work has been done to characterize T cell responses post transplant, bioluminesc...

  6. Intestinal barrier loss as a critical pathogenic link between inflammatory bowel disease and graft-versus-host disease.

    Science.gov (United States)

    Nalle, S C; Turner, J R

    2015-07-01

    Compromised intestinal barrier function is a prominent feature of inflammatory bowel disease (IBD). However, links between intestinal barrier loss and disease extend much further, including documented associations with celiac disease, type I diabetes, rheumatoid arthritis, and multiple sclerosis. Intestinal barrier loss has also been proposed to have a critical role in the pathogenesis of graft-versus-host disease (GVHD), a serious, potentially fatal consequence of hematopoietic stem cell transplantation. Experimental evidence has begun to support this view, as barrier loss and its role in initiating and establishing a pathogenic inflammatory cycle in GVHD is emerging. Here we discuss similarities between IBD and GVHD, mechanisms of intestinal barrier loss in these diseases, and the crosstalk between barrier loss and the immune system, with a special focus on natural killer (NK) cells. Unanswered questions and future research directions on the topic are discussed along with implications for treatment.

  7. TGF-β Codon 25 Polymorphism and the Risk of Graft-Versus-Host Disease after Allogenic Hematopoietic Stem Cell Transplantation

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    Ali Rashidi–Nezhad

    2010-03-01

    Full Text Available Some of the genotypes of cytokines are associated with acute graft versus host disease after bone marrow transplantation. The purpose of the present investigation was to find out the possible association between transforming growth factor beta-1 (TGF-β1 codon 25 polymorphism (rs:1800471 and acute graft versus host disease (aGVHD after bone marrow transplantation from the sibling with the similar HLA among the Iranian population. In this retrospective case-control investigation, 172 subjects including 86 Iranian patients and their siblings with the similar HLA as donor/recipient pairs were recruited. All of the patients were diagnosed with one group of blood disorder consisting of Acute Myeloid Leukemia (AML=40, Acute Lymphoblastic Leukemia (ALL=25 and Chronic Myeloid Leukemia (CML=21. PCR-SSP method was carried out to ascertain TGF- β1 codon 25 G/C polymorphism genotypes. The frequency of TGF- β1 codon 25 GG, GC and CC genotypes among all cases were 77.3%, 21.5% and 1.2%, respectively. Recipients with the GG genotype developed severe aGVHD significantly more than those with CC or GC genotypes (Odds Ratio =12.133, P=0.015. Genetic background of TGF-β1 may be involved in aGVHD development and/or severity in the patients who received Bone Marrow Transplantation (BMT from their siblings with the similar HLA among the Iranian population.

  8. Graft-versus-host disease after liver transplantation: A comprehensive literature review

    Institute of Scientific and Technical Information of China (English)

    Sami Akbulut; Mehmet Yilmaz; Sezai Yilmaz

    2012-01-01

    AIM:To determine the factors affecting mortality in patients who developed graft-versus-host disease (GvHD) after liver transplantation (LT).METHODS:We performed a review of studies of GvHD following LT published in the English literature and accessed the PubMed,Medline,EBSCO,EMBASE,and Google Scholar databases.Using relevant search phrases,88 articles were identified.Of these,61 articles containing most of the study parameters were considered eligible for the study.Risk factors were first examined using a univariate Kaplan-Meier model,and variables with a significant association (P < 0.05) were then subjected to multivariate analyses using a Cox proportional-hazards model.RESULTS:The 61 articles reported 87 patients,58 male and 29 female,mean age,40.4 ± 15.5 years (range:8 mo to 74 years),who met the inclusion criteria for the present study.Deaths occurred in 59 (67.8%) patients,whereas 28 (32.2%) survived after a mean follow-up period of 280.8 ± 316.2 d (range:27-2285 d).Among the most frequent symptoms were rash (94.2%),fever (66.6%),diarrhea (54%),and pancytopenia (54%).The average time period between LT and first symptom onset was 60.6 ± 190.1 d (range:2-1865 d).The Kaplan-Meier analysis revealed that pancytopenia (42.8% vs 59.3%,P =0.03),diarrhea (39.2% vs 61.0%,P =0.04),age difference between the recipient and the donor (14.6 ± 3.1 years vs 22.6 ± 2.7 years,P < 0.0001),and time from first symptom occurrence to diagnosis or treatment (13.3 ± 2.6 mo vs 15.0 ± 2.3 mo,P < 0.0001) were significant factors affecting mortality,whereas age,sex,presence of rash and fever,use of immunosuppressive agents,acute rejection before GvHD,etiological causes,time of onset,and donor type were not associated with mortality risk.The Cox proportional-hazards model,determined that an age difference between the recipient and donor was an independent risk factor (P =0.03;hazard ratio,7.395,95% confidence interval,1.2-46.7).CONCLUSION:This study

  9. Ocular graft versus host disease in allogenic haematopoetic stem cell transplantation in a tertiary care centre in India

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    Rehan Khan

    2015-01-01

    Full Text Available Background & objectives: This study was aimed to report the occurrence of ocular graft versus host disease (oGVHD in allogeneic haematopoietic stem cell transplantation (allo-HSCT patients in a tertiary care hospital setting. Methods: A cross-sectional study of ocular surface of allo-HSCT patients was done. Slit lamp biomicroscopy, symptom score, tear meniscus height, fluorescein tear break-up time, Schirmer′s test I, ocular surface staining, dry eye severity, ocular surface disease index score were done. Indications for allo-HSCT, human leukocyte antigen (HLA matching, GVHD risk factor, systemic manifestation and treatment were also noted. Results: GVHD occurred in 44.4 per cent of 54 allo-HSCT patients (mean age 26.7 ± 12 yr included in the study. GVHD risk factors identified included female gender, relapse, older age of donor, cytomagelo virus (CMV reactivation, and multiparous female donors. oGVHD was noted in 31.5 per cent with mean time to occurrence being 17.8 ± 21.9 months after the allo-HSCT and was observed in 89.5 per cent of chronic GVHD cases. Acute GVHD (oral and dermatological involvement showed a significant association with GVHD in our patients (P< 0.001, 0R 23.0, CI 6.4-82.1. Chronic GVHD was observed to be associated with the occurrence of oGVHD (dry eye (P<0.001, OR = 24.0, CI 0.02 - 0.29. Of the 34 eyes with oGHVD, dry eye of level 3 severity was seen in 16, level 2 in six, level 1 in 12 eyes. Interpretation & conclusions: GVHD occurred in 44.4 per cent of the patients studied in the present study. Acute and chronic GVHD showed a strong association with oGVHD. Dry eye disease due to chronic oGVHD was observed in 17 (31.5% of 54 allo-HSCT patient with chronic oGVHD occurring in 17 (89.4% of chronic GVHD cases in allo-HSCT patients. Our study on oGVHD in post allo-HSCT patients in tertiary care centre points towards the fact that ocular morbidity due to dry eye disease as a result of oGVHD is a cause for concern in these

  10. 桂附地黄丸干预主要组织相容性复合物半相合移植小鼠慢性移植物抗宿主病的效应%Effect of Guifu rehmaniae bolus on preventing chronic graft versus host disease in major histocompatibilty complex halpo-identical bone marrow transplantation mice

    Institute of Scientific and Technical Information of China (English)

    吴顺杰; 梁凯雯; 吴远彬; 周健; 涂三芳

    2012-01-01

    BACKGROUND: At present, the method for the treatment of chronic graft versus host disease is not ideal due the adverse reactions, founding the traditional Chinese medicine for effective intervention and treatment of chronic graft versus host disease is one of the common focuses of attention for the transplant scholars. OBJECTIVE: To observe effect of Guifu rehmaniae bolus on preventing chronic graft versus host disease in major histocompatibilty complex halpo-identical bone marrow transplantation mice. METHODS: Transplantation models of major histocompatibilty complex halpo-identical hematopoietic stem cells transplantation mice were established by transplanting the hematopoietic stem cells of male Balb/cH-2d mice to female (Balb/cxC57BL/6) F1 H-2d/b (CB6F1) mice. After transplantation, 24 recipient mice were divided into two groups: Guifu rehmaniae bolus group and blank group, mice in the Guifu rehmaniae bolus group were lavaged from the first day after transplantation with 0.2 mL Guifu rehmaniae bolus liquid twice per day; mice in the blank group were lavaged with the same dose of normal saline and lasted for 100 days. RESULTS AND CONCLUSION: Five mice died in the Guifu rehmaniae bolus group, and all mice died in the blank group at 86 days after transplantation (P=0.004). The mice in the blank group depressed at 35 days after transplantation and the mice in the Guifu rehmaniae bolus group depressed at 45 days after transplantation, and the clinical score in the blank group was significantly higher than that in the Guifu rehmaniae bolus group (P < 0.05). Pathological observation showed that the mice with chronic graft versus host disease in Guifu rehmaniae bolus group mostly classified from 0 to 1 grade. Compared with blank group, the liver, skin and small intestine tissue of the mice in Guifu rehmaniae bolus group were improved. Guifu rehmaniae bolus can relieve symptoms of chronic graft versus host disease in major histocompatibilty complex halpo-identical bone

  11. Chronic inflammatory demyelinating polyradiculoneuropathy in chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: case report Polirradiculoneuropatia desmielinizante inflamatória crônica na doença do enxerto contra o hospedeiro após transplante de células hematopoiéticas alogênicas: relato de caso

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    Paulo José Lorenzoni

    2007-09-01

    Full Text Available The chronic inflammatory demyelinating polyradiculoneuropathy (CIDP is an unusual but important complication of hematopoietic stem cell transplantation (HSCT rarely reported to date. We describe a 17-year-old woman with a diagnosis of acute myeloid leukemia due to Fanconi's anemia who was submitted to allogeneic HSCT and developed CIDP as part of graft-versus-host disease. Investigation showed high cerebrospinal fluid protein; electrophysiological studies revealed sensory-motor demyelinating polyradiculoneuropathy; muscle and nerve biopsy were compatible with CIDP.A polirradiculoneuropatia desmielinizante inflamatória crônica (CIDP é uma incomum, porém, importante complicação do transplante de células hematopoiéticas (HSCT raramente relatada até a data. Nós descrevemos uma mulher de 17 anos com diagnóstico de leucemia mielóide aguda por anemia de Fanconi que foi submetida à HSCT e desenvolveu CIDP como parte da doença do enxerto contra o hospedeiro. A investigação mostrou elevação na proteína no líquor; estudo eletrofisiológico revelando polirradiculoneuropatia desmielinizante sensitivo-motora; e biópsia de músculo e nervo compatível com CIDP.

  12. Substitution of methotrexate with corticosteroid for acute graft-versus-host disease prevention in transplanted patients who develop methotrexate toxicity.

    Science.gov (United States)

    Kim, Sung-Yong; Kim, Ah Ran; Yoon, So Young; Cho, Yo-Han; Lee, Mark Hong

    2016-02-01

    Methotrexate (MTX) toxicity can hamper the administration of all planned doses in acute graft-versus-host disease (GVHD) prophylaxis following allogeneic hematopoietic stem cell transplantation. Reduction or omission of MTX doses results in an increased risk of acute GVHD. In this prospective observational study, we compared the incidence of GVHD and the transplant outcomes between patients who received the full treatment course of MTX (group 1), patients in whom MTX doses were omitted if MTX toxicity developed (group 2), and patients receiving corticosteroid instead of MTX if MTX toxicity developed (group 3). The cumulative incidence of grades II-IV acute GVHD at 100 days post-transplantation was 22.2 % in group 1, 43.6 % in group 2, and 25.0 % in group 3 (P = 0.132). The risk of grades II-IV acute GVHD in group 2 was higher than that in group 1 (hazard ratio (HR) 3.262, P = 0.016), but the risk in group 3 was similar to that in group 1 (HR 0.960, P = 0.890). Group 3 also showed a trend towards a lower risk of chronic GVHD compared to the other groups. The cumulative risk of chronic GVHD at 2 years was 73.9, 71.6, and 33.3 % in groups 1, 2, and 3, respectively (P = 0.084). However, a likely higher relapse incidence and infection-related mortality in group 3 produced a trend towards the lowest relapse-free survival (2-year RFS, 46.3, 49.3, and 25.0 % in groups 1, 2, and 3, respectively; P = 0.329) and overall survival (2-year OS, 45, 52.3, and 25 %, respectively; P = 0.322) in group 3. Although the substitution of MTX with corticosteroid ameliorates the increased risk of GVHD in patients in which it is imperative to omit its dose, its negative impact on relapse and infection risk does not result in favorable transplant outcomes.

  13. The Role of Biomarkers in the Diagnosis and Risk Stratification of Acute Graft-versus-Host Disease: A Systematic Review.

    Science.gov (United States)

    Ali, Alaa M; DiPersio, John F; Schroeder, Mark A

    2016-09-01

    Allogeneic hematopoietic cell transplantation (HCT) is an increasingly used curative modality for hematologic malignancies and other benign conditions. Attempts to reduce morbidity and mortality and improve survival in patients undergoing HCT are crucial. The ability to diagnose acute graft-versus-host disease (aGVHD) in a timely manner, or to even predict aGVHD before clinical manifestations, along with the accurate stratification of these patients, are critical steps to improve the treatment and outcomes of these patients. Many novel biomarkers that may help achieve these goals have been studied recently. This overview is intended to assist clinicians and investigators by providing a comprehensive review and analytical interpretation of the current knowledge concerning aGVHD and biomarkers likely to prove useful in diagnosis and risk stratification of this condition, along with the difficulties that hamper this approach. PMID:27158050

  14. Bortezomib for the prevention and treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Al-Homsi, Ahmad Samer; Feng, Yuxin; Duffner, Ulrich; Al Malki, Monzr M; Goodyke, Austin; Cole, Kelli; Muilenburg, Marlee; Abdel-Mageed, Aly

    2016-09-01

    Allogeneic hematopoietic stem cell transplantation is the standard treatment for a variety of benign and malignant conditions. However, graft-versus-host disease (GvHD) continues to present a major barrier to the success and wide applicability of this procedure. Although current GvHD prevention and treatment regimens exclusively target T cells, bortezomib, a reversible proteasome inhibitor, possesses unique immune regulatory activities that span a wide variety of cellular processes of T and dendritic cells essential for the development of GvHD. Herein, we review the current understanding of the effects of bortezomib in vitro and in animal models and summarize the clinical data relevant to its use in the prevention and treatment of GvHD. We conclude with an outline of the remaining challenges and opportunities to optimize bortezomib's potential role in this setting. PMID:27224851

  15. Prevention of graft-versus-host disease by a novel immunosuppressant LLT, through expansion of regulatory T cells

    Institute of Scientific and Technical Information of China (English)

    WeiTANG; RuZHOU; Pei-lanHE; Xiao-yuLI; Yi-fuYANG; Jian-pingZUO

    2005-01-01

    AIM To evaluate the validity of LLT in prevention and therapy of acute graft versus host disease and to clarify the underlying mechanisms. LLT is a new compound derived from triptolide, which is the major immunosuppressive fraction of Tripterygium wilfordii Hook. F (TWHF). Studies in vitro and in vivo demonstrated that LLT had potent immunosuppressive activities. Here we tested the immunosuppressive effects of LLT in murine allogeneic bone marrow transplantation (BMT) and investigated the mechanisms underlying its suppressive effects. METHODS LLT was administered to recipients in BALB/cA→C57BL/6 murine BMT model, in which donor and recipient differ at major and minor histocompatibility antigens.Survival and weight change were recorded in recipients after alloBMT. Spleen size, chimerism and splenic T cell subpopulation were analysed by using flow cytometry.

  16. Expression profiling of major histocompatibility and natural killer complex genes reveals candidates for controlling risk of graft versus host disease.

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    Peter Novota

    Full Text Available BACKGROUND: The major histocompatibility complex (MHC is the most important genomic region that contributes to the risk of graft versus host disease (GVHD after haematopoietic stem cell transplantation. Matching of MHC class I and II genes is essential for the success of transplantation. However, the MHC contains additional genes that also contribute to the risk of developing acute GVHD. It is difficult to identify these genes by genetic association studies alone due to linkage disequilibrium in this region. Therefore, we aimed to identify MHC genes and other genes involved in the pathophysiology of GVHD by mRNA expression profiling. METHODOLOGY/PRINCIPAL FINDINGS: To reduce the complexity of the task, we used genetically well-defined rat inbred strains and a rat skin explant assay, an in-vitro-model of the graft versus host reaction (GVHR, to analyze the expression of MHC, natural killer complex (NKC, and other genes in cutaneous GVHR. We observed a statistically significant and strong up or down regulation of 11 MHC, 6 NKC, and 168 genes encoded in other genomic regions, i.e. 4.9%, 14.0%, and 2.6% of the tested genes respectively. The regulation of 7 selected MHC and 3 NKC genes was confirmed by quantitative real-time PCR and in independent skin explant assays. In addition, similar regulations of most of the selected genes were observed in GVHD-affected skin lesions of transplanted rats and in human skin explant assays. CONCLUSIONS/SIGNIFICANCE: We identified rat and human MHC and NKC genes that are regulated during GVHR in skin explant assays and could therefore serve as biomarkers for GVHD. Several of the respective human genes, including HLA-DMB, C2, AIF1, SPR1, UBD, and OLR1, are polymorphic. These candidates may therefore contribute to the genetic risk of GVHD in patients.

  17. A comparative review of methods for T cell depletion in the prophylaxis of graft-versus-host disease.

    Science.gov (United States)

    Hertenstein, B; Arseniev, L; Novotny, J; Ganser, A

    1998-02-01

    Graft-versus-host disease (GVHD) remains the major problem to be overcome in transplantation of allogeneic haemopoietic stem cells. Using immunosuppressive prophylaxis with cyclosporin and methotrexate, moderate to severe acute GVHD develops in approximately 45% of transplant recipients with an HLA-identical sibling donor and in >75% of patients from unrelated HLA-identical or partially matched related donors. The pathophysiology of GVHD is complex and still incompletely described. Experimental and clinical data indicate that GVHD is largely mediated by immunocompetent T cells in the donor stem cell graft which are reactive against recipient (host) tissues. Depletion of these immunocompetent T cells from the stem cell graft offers a way to effectively prevent GVHD. The first section of this review describes the technical principles of different methods of T cell depletion. The advantages, limitations and level of T cell depletion achievable by physical methods or by positive and negative immunoselection procedures using monoclonal antibodies are comprehensively discussed. A short section concentrates on technical problems in the enumeration of T cells in the context of depletion efficiency. In the section on clinical studies, the focus is on the efficacy of different T cell depletion methods in avoiding GVHD in different clinical settings. The various methods are compared in transplantation from HLA-identical and nonidentical siblings or matched unrelated donors. The major drawbacks of T cell depletion are discussed in detail. Failure of engraftment and graft rejection is a more frequent problem following T cell-depleted transplants, particularly with HLA nonidentical donor-recipient pairs. An increase in leukaemic relapse rate is seen in certain haematological malignancies, especially in chronic myeloid leukaemia. Delayed recovery of anti-infectious immunity occurs, leading to an increased incidence of cytomegalovirus and Epstein-Barr virus related problems. The

  18. Biomarkers for the detection of graft-versus-host disease in cancer patients after bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Paczesny S

    2012-08-01

    Full Text Available Sophie PaczesnyDepartment of Pediatrics, University of Michigan, Ann Arbor, MI, USAAbstract: Allogeneic hematopoietic stem cell transplantation (HSCT is the most effective form of tumor immunotherapy available to date, and the frequency of transplants continues to increase worldwide. However, while allogeneic HSCT can induce beneficial graft-versus-tumor (GVT effects, the adverse effect of graft-versus-host disease (GVHD, which is closely linked to GVT, is the major source of morbidity and mortality following HSCT. Acute GVHD (aGVHD develops when the donor's immune cells from the graft attack the patient's skin, liver, or intestines. Target organs involved in chronic GVHD (cGVHD are variable, resemble autoimmune manifestations, and typically include skin; mucosa (mouth, eyes, genitalia; muscles/fascia/joints; lungs; and gastrointestinal tract/liver. GVHD occurs in two forms, classically distinguished as aGVHD, beginning before day 100 after HSCT, and cGVHD, occurring after day 100, although it is now accepted that these are two separate pathophysiologic entities. Currently available diagnostic and staging tools frequently fail to identify those at higher risk of GVHD progression, unresponsiveness to different forms of therapy, or death. Furthermore, there are shortcomings in the prediction of the future occurrence of GVHD before clinical signs develop. In parallel, in recent years there has been an explosive evolution of proteomics technologies, largely due to important advances in chemistry, engineering, high-throughput technical devices, and bioinformatics. Building on these opportunities, plasma biomarkers have been identified and validated both as promising diagnostic tools of GVHD and as prognostic tools for nonrelapse mortality. These biomarkers might facilitate timely and selective therapeutic intervention. However, such biomarkers should be more widely validated and incorporated into a new grading system to risk-stratify patients and

  19. 慢性移植物抗宿主病相关性多发性肌炎一例临床和骨骼肌病理特点%Clinical and muscular pathological features with chronic graft-versus-host disease-related polymyositis: one case report

    Institute of Scientific and Technical Information of China (English)

    孟令超; 张巍; 王朝霞; 高枫; 袁云

    2012-01-01

    Objective To report the clinical and pathological features of chronic graft-versus-host disease-related polymyositis by summarizing the clinical data of the patient with chronic graft-versus-host disease-related polymyositis. Methods One patient with chronic graft-versus-host disease-related polymyositis was hospitalized in our hospital on December 29,2010.The patient,40 years old,female,underwent allogeneic haematopoietic stem cell transplantation because of acute granulocytic-monocytic leukemia.Fourteen months later she manifested as slowly progressive muscle weakness and myalgia in all limbs.Serum creatine kinase level was between 426-1948 U/L. Myositis antibody EJ was strongly positive.Electromyogram showed a neurogenic impairment and slow peripheral nerve conduction speed.Muscle biopsies were carried out in the left biceps brechii.In addition of standard histological and enzyme histochemical staining for the muscle sections,immunohistochemical workup was performed with mouse antiCDs,anti-CD20,anti-CD68 and anti major histocompatibility complex- Ⅰ ( MHC- Ⅰ ) monoclonal antibodies as first antibodies.Results The muscle biopsy showed large variation of fiber size,with muscle fiber necrosis,regeneration.Some angular fibers distributed in small cluster.The inflammatory cells infiltrated around the small vessel or in the endomysium,mainly CD8+ T-lymphocytes and CD6+8 macrophages.The most muscle fibers were MHC-Ⅰ positive. Conclusion The graft-versus-host disease-related polymyositis manifests as chronic myositis process with neurogenic lesions.%目的 报道1例慢性移植物抗宿主病相关性多发性肌炎患者的临床和骨骼肌病理改变特点.方法 我院于2010年12月29日收治1例慢性移植物抗宿主病相关性多发性肌炎患者,该患者为女性,40岁,因急性粒单核细胞白血病于20个月前行异基因造血干细胞移植术.术后给予环孢素A抗排异治疗13个月,6个月前缓慢出现进行性四肢近端无力,

  20. The role of programmed cell death ligand-1 (PD-L1/CD274 in the development of graft versus host disease.

    Directory of Open Access Journals (Sweden)

    Heevy Al-Chaqmaqchi

    Full Text Available Programmed cell death ligand-1 (PD-L1/CD274 is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues plays a protective role in skeletal muscle during acute graft-versus-host disease.

  1. Possible implication of bacterial infection in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Shigeo eFuji

    2014-04-01

    Full Text Available Graft-versus-host disease (GVHD is still one of the major causes of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (HSCT. In the pathogenesis of acute GVHD, it has been established that donor-derived T cells activated in the recipient play a major role in GVHD in initiation and maintenance within an inflammatory cascade. To reduce the risk of GVHD, intensification of GVHD prophylaxis like T cell depletion is effective, but it inevitably increases the risk of infectious diseases and abrogates beneficial graft-versus-leukemia effects. Although various cytokines are considered to play an important role in the pathogenesis of GVHD, GVHD initiation is such a complex process that cannot be prevented by means of single inflammatory cytokine inhibition. Thus, efficient methods to control the whole inflammatory milieu both on cellular and humoral view are needed. In this context, infectious diseases can theoretically contribute to an elevation of inflammatory cytokines after allogeneic HSCT and activation of various subtypes of immune effector cells, which might in summary lead to an aggravation of acute GVHD. The appropriate treatments or prophylaxis of bacterial infection during the early phase after allogeneic HSCT might be beneficial to reduce not only infectious-related but also GVHD-related mortality. Here, we aim to review the literature addressing the interactions of bacterial infections and GVHD after allogeneic HSCT.

  2. Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease.

    Science.gov (United States)

    Mathewson, Nathan D; Jenq, Robert; Mathew, Anna V; Koenigsknecht, Mark; Hanash, Alan; Toubai, Tomomi; Oravecz-Wilson, Katherine; Wu, Shin-Rong; Sun, Yaping; Rossi, Corinne; Fujiwara, Hideaki; Byun, Jaeman; Shono, Yusuke; Lindemans, Caroline; Calafiore, Marco; Schmidt, Thomas C; Honda, Kenya; Young, Vincent B; Pennathur, Subramaniam; van den Brink, Marcel; Reddy, Pavan

    2016-05-01

    The effect of alterations in intestinal microbiota on microbial metabolites and on disease processes such as graft-versus-host disease (GVHD) is not known. Here we carried out an unbiased analysis to identify previously unidentified alterations in gastrointestinal microbiota-derived short-chain fatty acids (SCFAs) after allogeneic bone marrow transplant (allo-BMT). Alterations in the amount of only one SCFA, butyrate, were observed only in the intestinal tissue. The reduced butyrate in CD326(+) intestinal epithelial cells (IECs) after allo-BMT resulted in decreased histone acetylation, which was restored after local administration of exogenous butyrate. Butyrate restoration improved IEC junctional integrity, decreased apoptosis and mitigated GVHD. Furthermore, alteration of the indigenous microbiota with 17 rationally selected strains of high butyrate-producing Clostridia also decreased GVHD. These data demonstrate a heretofore unrecognized role of microbial metabolites and suggest that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and can mitigate disease severity.

  3. Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease.

    Science.gov (United States)

    Mathewson, Nathan D; Jenq, Robert; Mathew, Anna V; Koenigsknecht, Mark; Hanash, Alan; Toubai, Tomomi; Oravecz-Wilson, Katherine; Wu, Shin-Rong; Sun, Yaping; Rossi, Corinne; Fujiwara, Hideaki; Byun, Jaeman; Shono, Yusuke; Lindemans, Caroline; Calafiore, Marco; Schmidt, Thomas C; Honda, Kenya; Young, Vincent B; Pennathur, Subramaniam; van den Brink, Marcel; Reddy, Pavan

    2016-05-01

    The effect of alterations in intestinal microbiota on microbial metabolites and on disease processes such as graft-versus-host disease (GVHD) is not known. Here we carried out an unbiased analysis to identify previously unidentified alterations in gastrointestinal microbiota-derived short-chain fatty acids (SCFAs) after allogeneic bone marrow transplant (allo-BMT). Alterations in the amount of only one SCFA, butyrate, were observed only in the intestinal tissue. The reduced butyrate in CD326(+) intestinal epithelial cells (IECs) after allo-BMT resulted in decreased histone acetylation, which was restored after local administration of exogenous butyrate. Butyrate restoration improved IEC junctional integrity, decreased apoptosis and mitigated GVHD. Furthermore, alteration of the indigenous microbiota with 17 rationally selected strains of high butyrate-producing Clostridia also decreased GVHD. These data demonstrate a heretofore unrecognized role of microbial metabolites and suggest that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and can mitigate disease severity. PMID:26998764

  4. Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease

    Science.gov (United States)

    Le Texier, Laëtitia; Lineburg, Katie E.; Leveque-El Mouttie, Lucie; Nicholls, Jemma; Melino, Michelle; Nalkurthi, Blessy C.; Alexander, Kylie A.; Teal, Bianca; Blake, Stephen J.; Souza-Fonseca-Guimaraes, Fernando; Engwerda, Christian R.; Kuns, Rachel D.; Lane, Steven W.; Teh, Charis; Gray, Daniel; Clouston, Andrew D.; Nilsson, Susan K.; Blazar, Bruce R.; Hill, Geoffrey R.; MacDonald, Kelli P.A.

    2016-01-01

    Regulatory T cells (Tregs) play a crucial role in the maintenance of peripheral tolerance. Quantitative and/or qualitative defects in Tregs result in diseases such as autoimmunity, allergy, malignancy, and graft-versus-host disease (GVHD), a serious complication of allogeneic stem cell transplantation (SCT). We recently reported increased expression of autophagy-related genes (Atg) in association with enhanced survival of Tregs after SCT. Autophagy is a self-degradative process for cytosolic components that promotes cell homeostasis and survival. Here, we demonstrate that the disruption of autophagy within FoxP3+ Tregs (B6.Atg7fl/fl-FoxP3cre+) resulted in a profound loss of Tregs, particularly within the bone marrow (BM). This resulted in dysregulated effector T cell activation and expansion, and the development of enterocolitis and scleroderma in aged mice. We show that the BM compartment is highly enriched in TIGIT+ Tregs and that this subset is differentially depleted in the absence of autophagy. Moreover, following allogeneic SCT, recipients of grafts from B6.Atg7fl/fl-FoxP3cre+ donors exhibited reduced Treg reconstitution, exacerbated GVHD, and reduced survival compared with recipients of B6.WT-FoxP3cre+ grafts. Collectively, these data indicate that autophagy-dependent Tregs are critical for the maintenance of tolerance after SCT and that the promotion of autophagy represents an attractive immune-restorative therapeutic strategy after allogeneic SCT. PMID:27699243

  5. Lithothamnion muelleri Controls Inflammatory Responses, Target Organ Injury and Lethality Associated with Graft-versus-Host Disease in Mice

    Science.gov (United States)

    Rezende, Barbara M.; Bernardes, Priscila T. T.; Resende, Carolina B.; Arantes, Rosa M. E.; Souza, Danielle G.; Braga, Fernão C.; Castor, Marina G. M.; Teixeira, Mauro M.; Pinho, Vanessa

    2013-01-01

    Lithothamnion muelleri (Hapalidiaceae) is a marine red alga, which is a member of a group of algae with anti-inflammatory, antitumor, and immunomodulatory properties. The present study evaluated the effects of treatment with Lithothamnion muelleri extract (LM) in a model of acute graft-versus-host disease (GVHD), using a model of adoptive splenocyte transfer from C57BL/6 donors into B6D2F1 recipient mice. Mice treated with LM showed reduced clinical signs of disease and mortality when compared with untreated mice. LM-treated mice had reduced tissue injury, less bacterial translocation, and decreased levels of proinflammatory cytokines and chemokines (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5)). The polysaccharide-rich fraction derived from LM could inhibit leukocyte rolling and adhesion in intestinal venules, as assessed by intravital microscopy. LM treatment did not impair the beneficial effects of graft-versus-leukaemia (GVL). Altogether, our studies suggest that treatment with Lithothamnion muelleri has a potential therapeutic application in GVHD treatment. PMID:23873335

  6. Magnetic resonance enterography for assessment of intestinal graft-versus-host disease after allogeneic stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Hanover Medical School, Department of Nuclear Medicine, Hanover (Germany); Laqmani, Azien; Adam, Gerhard; Bannas, Peter [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Veldhoen, Simon [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); University Medical Center Wuerzburg, Department of Diagnostic and Interventional Radiology, Wuerzburg (Germany); Apostolova, Ivayla [Otto-von-Guericke University, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Ayuk, Francis; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation, Hamburg (Germany)

    2015-05-01

    To determine the diagnostic performance of MR enterography (MRE) for detection and grading of gastrointestinal graft-versus-host disease (GI GvHD) after hematopoietic stem cell transplantation (SCT). Forty-one patients with known GvHD or suspected GvHD underwent MRE and GI endoscopy with multi-level biopsies. MRE images were reviewed for presence of intestinal wall inflammation. Clinical grading of GI GvHD was performed. Histopathological evaluation (HPE) served as the reference standard. Overall, MRE demonstrated a per-patient sensitivity of 81.5 % for detection of GI GvHD. The most common findings were intestinal wall thickening (81.5 % of GvHD patients), luminal stenosis (81.5 %), mural contrast enhancement (70.4 %), and ascites (59.3 %). These findings were also observed in other conditions than GvHD. The most frequently involved intestinal segment was the sigmoid colon (63.0 %), followed by the ileum (59.3 %) and the jejeunum (51.9 %). The number of involved segments (r{sub s} =0.54, p =0.009) correlated significantly with clinical severity as determined by GvHD grading. After allogeneic stem cell transplantation, MRE may (1) contribute to detection and localization of GI GvHD, and (2) add information indicating the clinical severity of disease, but findings are unspecific. False negative results may be observed not only in low-grade GI GvHD. (orig.)

  7. Role of small-dose decitabine in treatment of early recurrence and chronic graft versus host disease after allogeneic hematopoietic stem cell transplantation%小剂量地西他滨在异基因造血干细胞移植后早期复发及cGVHD治疗中的作用

    Institute of Scientific and Technical Information of China (English)

    王晓果; 陈婷; 刘焕凤; 邓天霞; 刘俊; 张诚; 张曦; 孔佩艳

    2016-01-01

    目的 分析小剂量地西他滨(decitabine/dacogen,DAC)治疗异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后慢性移植物抗宿主病(chronic graft versus host disease,cGVHD)患者的转归情况.方法 收集2013年6月25日至2015年7月7日我院行allo-HSCT术后早期复发及发生cGVHD,并接受小剂量DAC治疗的4例患者,包括急性髓系白血病(acute myeloid leukemia,AML)3例,骨髓增生异常综合征(myelodysplastic syndrome,MDS)1例.对其诊断、移植方式、cGVHD分型及评分、以及DAC治疗后转归进行分析.结果 4例接受小剂量DAC的患者,cGVHD症状减轻,无严重的血液学毒性.1例因严重肺部感染放弃治疗,3例目前病情稳定.结论 小剂量DAC可减轻allo-HSCT术后cGVHD症状,改善患者生存质量,并对早期复发的控制有一定的效果.

  8. IL-35 mitigates murine acute graft-versus-host disease with retention of graft-versus-leukemia effects.

    Science.gov (United States)

    Liu, Y; Wu, Y; Wang, Y; Cai, Y; Hu, B; Bao, G; Fang, H; Zhao, L; Ma, S; Cheng, Q; Song, Y; Liu, Y; Zhu, Z; Chang, H; Yu, X; Sun, A; Zhang, Y; Vignali, D A A; Wu, D; Liu, H

    2015-04-01

    IL-35 is a newly discovered inhibitory cytokine secreted by regulatory T cells (Tregs) and may have therapeutic potential in several inflammatory disorders. Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation and caused by donor T cells and inflammatory cytokines. The role of IL-35 in aGVHD is still unknown. Here we demonstrate that IL-35 overexpression suppresses CD4(+) effector T-cell activation, leading to a reduction in alloreactive T-cell responses and aGVHD severity. It also leads to the expansion of CD4(+)Foxp3(+) Tregs in the aGVHD target organs. Furthermore, IL-35 overexpression results in a selective decrease in the frequency of Th1 cells and an increase of IL-10-producing CD4(+) T cells in aGVHD target tissues. Serum levels of TNF-α, IFN-γ, IL-6, IL-22 and IL-23 decrease and IL-10 increases in response to IL-35. Most importantly, IL-35 preserves graft-versus-leukemia effect. Finally, aGVHD grade 2-4 patients have decreased serum IL-35 levels comparing with time-matched patients with aGVHD grade 0-1. Our findings indicate that IL-35 has an important role in reducing aGVHD through promoting the expansion of Tregs and repressing Th1 responses, and should be investigated as the therapeutic strategy for aGVHD.

  9. Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Lorenz, Fryderyk; Marklund, Stefan; Werner, Mårten; Palmqvist, Richard; Wahlin, Björn Engelbrekt; Wahlin, Anders

    2015-01-01

    The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The aim of fecal calprotectin and alpha-1 antitrypsin testing in our study was to find out whether determination of the concentrations of these proteins may be used as a screening method for enteric GVHD. We studied prospectively 51 patients, 8 of whom developed GI-GVHD. Our data demonstrate that elevated fecal calprotectin levels were significantly associated with presence of GI-GVHD. We found a positive association between high F-calprotectin and severe gastrointestinal GVHD. In bivariate analysis, only calprotectin but not alpha-1 antitrypsin was independently associated with GI-GVHD. Testing for fecal calprotectin after allogeneic stem cell transplantation may be a useful screening tool. PMID:25605402

  10. Quantitative computed tomography assessment of graft-versus-host disease-related bronchiolitis obliterans in children: A pilot feasibility study

    International Nuclear Information System (INIS)

    To suggest a simple method that can quantify air trapping from chest CT in children with graft-versus-host disease (GVHD)-related bronchiolitis obliterans (BO). This institutional review board-approved retrospective study included eight GVHD-related BO patients (age, 6 - 17 years) who underwent both 31 CTs of variable settings and pulmonary function tests (PFT). The attenuation values of lung parenchyma in normal (An) and air trapping (Aa) areas were obtained. Individualized threshold [(An + Aa)/2] and fixed threshold of -950 HU were set for air trapping quantification. Spearman correlation analysis and generalized linear mixed models were used for statistical analysis. The mean value of individualized threshold was -830.2 ± 48.3 HU. The mean air trapping lung volume percentage with individualized threshold and -950 HU were 45.4 ± 18.9 % and 1.4 ± 1.9 %, respectively. The air trapping lung volume percentage with individualized threshold showed a significant negative correlation with the PFT of FEV1/FVC% in all data (γ = -0.795, P <.001) and in the correction of repetition (γ = -0.837, P =.010). We suggest a simple and individualized threshold attenuation setting method for air trapping quantification insusceptible to CT imaging protocols or respiratory phase control in children with GVHD-related BO. (orig.)

  11. Quantitative computed tomography assessment of graft-versus-host disease-related bronchiolitis obliterans in children: A pilot feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Gi [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, Severance Children' s Hospital, Seoul (Korea, Republic of); Ajou University Medical Center, Department of Radiology, Ajou University School of Medicine, Suwon (Korea, Republic of); Shin, Hyun Joo; Kim, Myung-Joon; Lee, Mi-Jung [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, Severance Children' s Hospital, Seoul (Korea, Republic of); Kim, Yoon Hee; Sohn, Myung Hyun; Kim, Kyung Won [Yonsei University College of Medicine, Department of Pediatrics and Institute of Allergy, Severance Children' s Hospital, Seoul (Korea, Republic of); Lyu, Chuhl Joo [Yonsei University College of Medicine, Department of Pediatric Hematology and Oncology, Severance Children' s Hospital, Seoul (Korea, Republic of)

    2015-10-15

    To suggest a simple method that can quantify air trapping from chest CT in children with graft-versus-host disease (GVHD)-related bronchiolitis obliterans (BO). This institutional review board-approved retrospective study included eight GVHD-related BO patients (age, 6 - 17 years) who underwent both 31 CTs of variable settings and pulmonary function tests (PFT). The attenuation values of lung parenchyma in normal (An) and air trapping (Aa) areas were obtained. Individualized threshold [(An + Aa)/2] and fixed threshold of -950 HU were set for air trapping quantification. Spearman correlation analysis and generalized linear mixed models were used for statistical analysis. The mean value of individualized threshold was -830.2 ± 48.3 HU. The mean air trapping lung volume percentage with individualized threshold and -950 HU were 45.4 ± 18.9 % and 1.4 ± 1.9 %, respectively. The air trapping lung volume percentage with individualized threshold showed a significant negative correlation with the PFT of FEV1/FVC% in all data (γ = -0.795, P <.001) and in the correction of repetition (γ = -0.837, P =.010). We suggest a simple and individualized threshold attenuation setting method for air trapping quantification insusceptible to CT imaging protocols or respiratory phase control in children with GVHD-related BO. (orig.)

  12. The MEK inhibitor trametinib separates murine graft-versus-host disease from graft-versus-tumor effects

    Science.gov (United States)

    Itamura, Hidekazu; Tawara, Isao; Kubota, Yasushi; Kariya, Ryusho; Okada, Seiji; Kimura, Shinya

    2016-01-01

    The efficacy of allogeneic hematopoietic stem cell transplantation for hematologic malignancies is limited by the difficulty in suppressing graft-versus-host disease (GVHD) without compromising graft-versus-tumor (GVT) effects. We previously showed that RAS/MEK/ERK signaling depends on memory differentiation in human T cells, which confers susceptibility to selective inhibition of naive T cells. Actually, antineoplastic MEK inhibitors selectively suppress alloreactive T cells, sparing virus-specific T cells in vitro. Here, we show that trametinib, a MEK inhibitor clinically approved for melanoma, suppresses GVHD safely without affecting GVT effects in vivo. Trametinib prolonged survival of GVHD mice and attenuated GVHD symptoms and pathology in the gut and skin. It inhibited ERK1/2 phosphorylation and expansion of donor T cells, sparing Tregs and B cells. Although high-dose trametinib inhibited myeloid cell engraftment, low-dose trametinib suppressed GVHD without severe adverse events. Notably, trametinib facilitated the survival of mice transplanted with allogeneic T cells and P815 tumor cells with no residual P815 cells observed in the livers and spleens, whereas tacrolimus resulted in P815 expansion. These results confirm that trametinib selectively suppresses GVHD-inducing T cells while sparing antitumor T cells in vivo, which makes it a promising candidate for translational studies aimed at preventing or treating GVHD.

  13. Novel Approaches for Graft-versus-Host Disease Prevention Compared to Contemporary Controls (BMT CTN 1203)

    Science.gov (United States)

    2016-06-16

    Acute Leukemia; Chronic Myelogenous Leukemia; Myelodysplasia; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Hodgkin's Lymphoma

  14. Xenogeneic Graft-versus-Host-Disease in NOD-scid IL-2Rγnull Mice Display a T-Effector Memory Phenotype

    OpenAIRE

    Niwa Ali; Barry Flutter; Robert Sanchez Rodriguez; Ehsan Sharif-Paghaleh; Barber, Linda D.; Giovanna Lombardi; Nestle, Frank O

    2012-01-01

    The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the N...

  15. IL-17 Gene Ablation Does Not Impact Treg-Mediated Suppression of Graft-Versus-Host Disease after Bone Marrow Transplantation

    OpenAIRE

    Colonna, Lucrezia; Florek, Mareike; Leveson-Gower, Dennis B.; Sega, Emanuela I.; Baker, Jeanette; Smith, Aaron T.; Negrin, Robert S.

    2013-01-01

    Regulatory T cell (Treg) immunotherapy is a promising strategy for the treatment of graft rejection responses and autoimmune disorders. Our and other laboratories have shown that the transfer of highly purified CD4+CD25+Foxp3+ natural Treg can prevent lethal graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation across both major and minor histocompatibility barriers. However, recent evidence suggests that the Treg suppressive phenotype can become unstable, a phe...

  16. Bone marrow transplantation in the rat. I. Histologic correlations and quantitation of cellular infiltrates in acute graft-versus-host disease.

    OpenAIRE

    Renkonen, R; Häyry, P.

    1984-01-01

    In an attempt to define which cytologic manifestations of inflammation are characteristic of acute graft-versus-host disease (aGVHD), the authors have analyzed hematologic reconstitution in the bone marrow, spleen, and blood of bone marrow transplant recipients and correlated these events to concomitant cytologic changes in the parenchymal target organs. After bone marrow transplantation from Lewis to BN strain, the strongest inflammatory changes were observed in the liver, a "model" parenchy...

  17. Rituximab in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

    Science.gov (United States)

    2014-05-28

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Graft Versus Host Disease; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III

  18. Incidence and Pattern of Graft-versus-Host Disease in Patients Undergoing Allogeneic Transplantation after Nonmyeloablative Conditioning with Total Lymphoid Irradiation and Antithymocyte Globulin

    Directory of Open Access Journals (Sweden)

    Lauren Veltri

    2013-01-01

    Full Text Available Nonmyeloablative (NMA conditioning with total lymphoid irradiation and antithymocyte globulin (TLI/ATG has been shown to protect against acute graft-versus-host disease (GVHD. We report here our institutional experience with allogeneic transplantation following NMA conditioning with TLI/ATG (. GVHD prophylaxis consisted of a combination of a calcineurin inhibitor and mycophenolate mofetil. Median patient age was 59 years. The median followup of surviving patients is 545 days. One patient experienced primary graft rejection. The median time to neutrophil engraftment was 18 days and platelet engraftment was 9.5 days. The cumulative incidence (CI of grade II–IV acute GVHD at day +100 was 28.6% and 38.1% at day +180. The CI for grade III-IV acute GVHD was 28.6% at day +180. CI of chronic GVHD was 45.2% at 1 year. The CI of disease relapse was 9.5% at 1 year. The rate of nonrelapse mortality (NRM was 0% at day +100 and only 9.5% at 1 year. The overall and progression free survival at 1 year was 81% and 80.4%, respectively. Our limited, retrospective data show encouraging relapse and NRM rates with TLI/ATG-based NMA conditioning, but with higher than previously reported rates of acute and chronic GVHD, underscoring the need for novel strategies designed to effectively prevent GVHD.

  19. Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission

    Science.gov (United States)

    2014-01-23

    B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Graft Versus Host Disease; L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  20. Cyclosporin-Methotrexate Compared with Cyclosporin-Methotrexate-Methylprednisolone Therapy for the Prophylaxis of Acute Graft-Versus Host Disease

    International Nuclear Information System (INIS)

    Acute graft-versus host (GVHD) disease is a common immunologic complication, which occurs in 40-50% of the recipients of allogenic stem cell transplantation (SCT). The role of corticosteroid in the prevention of GVHD is not well established. We report here a study to determine whether the addition of methylprednisolone to the combination of cyclosporine (CSA) and methotrexate (MTX), methylp-rednisolone (MP) for the prophylaxis of acute GVHD would further decrease the incidence of acute GVHD. A group of patients (25 patients with acute myeloid leukemia (AML) and 12 patients with acute lymphocytic leukemia (ALL) that received CSA/MTX/MP started from 2004 to 2008, were compared to a historical group of patients (19 patient with acute myeloid leukemia (AML) and 12 patients with acute lymphocytic leukemia (ALL) that received GVHD prophylaxis in the form of CSA/MTX only from 1999 to 2003). The primary endpoint in this study was the develop-ment of GVHD and the secondary end point was overall and disease free survival. Both groups of patients were matched for age, sex, donor recipient sex, low risk patients and high risk patients. Although the incidence of acute GVHD in the MP -ve group was 35% versus 24% in the MP+ve group, there was no significant difference between them. The overall survival showed a significant difference between the 2 groups (p<0.05). It was 48% for the 2 drug regimen (CSA/MTX) vs. 81% for the three drug regimen (CSA/MTX/MP). There was a significant decrease in the relapse rate in patients on CSA/MTX/MP (p<0.05). In conclusion, the addition of MP (methylprednis-olone) to the combination of CSA/MTX did not affect the incidence of acute GVHD significantly in allogeneic SCT but surprisingly the incidence of survival and relapse was markedly increased and decreased respectively

  1. The Role Of Interleukin - 18 And Interleukin – 2 Receptors In Acute Graft-Versus-Host Disease After Bone Marrow Transplantation

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    Iravani M

    2004-08-01

    Full Text Available Background: Graft-versus-host disease is one of the major complications after allogenic bone marrow transplantation, but it is not easy to anticipate the onset. Cytokines released by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus-host disease (aGVHD. The ability to predict the likely occurrence of graft-versus-host-disease (GVHD after BMT would be extremely valuable. By serially measuring serum levels of soluble IL-2 receptor (sIL-2R, IL-18 and following allogeneic bone marrow transplantation (BMT, we tried to define their relationship to aGVHD as complication of the transplantation and determine useful markers for aGVHD predictors. Materials and Methods: Serum sIL-2R, IL-18, and levels were measured by sandwich ELISA in 219 sera samples from 39 patients (with hematological disorders before and after allogeneic BMT and 28 controls. All patients received BMT from HLA-identical siblings. Results: 25 patients developed aGVHD and serum levels of sIL-2 R and IL-18 , in sera drawn before transplantation , in patients with acute graft-versus-host disease (aGVHD + , were increased in comparison of patients without acute graft-versus-host disease (aGVHD ¯ and control group and there wasn’t any significant differences in serum levels of sIL-2 R and IL-18 in aGVHD ¯ patients and controls. Serum level of IL-18, in aGVHD+ patients, was increased during day 3 - 24 after BMT, and there was a significant difference in patients with GVHD 0 – GVHD III. In majority of patients with acute GVHD (60 % , the peak levels of IL-18 and IL-2R was achieved on day 10 after BMT and the rise in sIL-2R and IL-18 preceded of clinical signs of GVHD (mean day 15 after BMT. Level of IL-18 in patients with aGVHD had strongly correlated with the severity of aGVHD on Day 10 after BMT. IL-18 level mean (before BMT, in patients who received Busulfan and Fludarabin to treat aGVHD, was lower than in patients who received Busulfan - Endoxan, or

  2. OMISSION OF DAY +11 METHOTREXATE DOES NOT APPEAR TO INFLUENCE INCIDENCE AND SEVERITY OF GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    朱康儿; 张涛; 陈盛亭; 钟隽; 曾慧兰

    2004-01-01

    Objective: To explore the influence of omission of the day +11 dose of methotrexate (MIX) on the incidence and severity of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: From April 1997 to October 2002, 80 leukemia patients (46 men and 34 women aged from 12 to 56 years with a median age of 35) underwent allo-HSCT at our BMT unit. Among them, 58 patients received grafts from HLA-identical siblings, 8 from HLA one major antigen mismatched siblings and 14 from HLA-matched unrelated donors. All patients received a modified cyclosporine and short-course MTX regimen for GVHD prophylaxis, which included MTX 15 mg on day +1, and 10 mg on days +3 and +6 (MTX day +11 dose omitted) and cyclosporine given daily. Results: The overall incidence of grade I~IV acute GVHD was 57.5% (46/80 patients), with grade II~IV acute GVHD in 28 patients (35%) and grade III~IV acute GVHD in 7 patients (8.8%). Among 58 patients receiving grafts from HLA-identical siblings, 24 patients developed grade I~IV acute GVHD (41.4%), with grade II~IV acute GVHD in 13 patients (22.4%) and grade III~IV acute GVHD in 4 patients (6.9%). 2l out of 22 patients receiving grafts from HLA one major antigen mismatched siblings and HLA-matched unrelated donors developed grade I~IV acute GVHD (95.5%), with grade II~IV acute GVHD in 14 patients (63.6%) and grade III~IV acute GVHD in 3 patients (13.6%). Chronic GVHD occurred in 38 out of 56 evaluable patients (67.9%), with extensive form in 15 patients (26.8%) and limited form in 23 patients (41.1%). With a median follow-up of 960 days (range 180~1980 days), the probability of leukemia-free survival at 3 years was 61.3% for all patients. Conclusion: Our results suggest that the day +11 MTX can be omitted without a major deleterious effect on the incidence and severity of graft-versus-host disease after HLA-identical sibling transplantation as well as HLA one major antigen mismatched sibling and HLA

  3. IL4RA on lymphatic endothelial cells promotes T cell egress during sclerodermatous graft versus host disease

    Science.gov (United States)

    Urso, Katia; Alvarez, David; Cremasco, Viviana; Tsang, Kelly; Grauel, Angelo; Lafyatis, Robert; von Andrian, Ulrich H.; Ermann, Joerg; Aliprantis, Antonios O.

    2016-01-01

    Systemic sclerosis (SSc) is a potentially fatal autoimmune disorder with limited therapeutic options. Sclerodermatous graft versus host disease (sclGvHD), induced by transfer of B10.D2 splenocytes into BALB/c Rag2−/− mice, models an inflammatory subset of SSc characterized by a prominent IL13-induced gene expression signature in the skin. Host mice deficient in IL4RA, a subunit of the type II IL4/IL13 receptor, are protected from sclGvHD. While IL4RA has a well-established role in Th2 differentiation and alternative macrophage activation, we report here a previously unappreciated function for IL4RA in lymphatic endothelial cells (LECs): regulation of activated T cell egress. Seven days after splenocyte transfer, Il4ra−/− hosts had increased numbers of activated graft CD4+ T cells in skin draining lymph nodes (dLNs) but fewer T cells in efferent lymph, blood, and skin. Sphingosine-1 phosphate (S1P), master regulator of lymphocyte egress from LNs, was lower in dLNs of Il4ra−/− hosts with a corresponding decrease of S1P kinase 1 (Sphk1) expression in LECs. Bypassing the efferent lymphatics via i.v. injection of CD4+ T cells from dLNs of Il4ra−/− sclGvHD mice restored clinical GvHD in secondary Il4ra−/− recipients. These results identify a role for IL4RA and suggest that modulation of lymphocyte egress from LNs may be effective in SSc and GvHD.

  4. MC1288, a vitamin D analog, prevents acute graft-versus-host disease in rat bone marrow transplantation.

    Science.gov (United States)

    Pakkala, I; Taskinen, E; Pakkala, S; Räisänen-Sokolowski, A

    2001-04-01

    The major obstacle to successful bone marrow transplantation (BMT) is graft-versus-host disease (GVHD). Vitamin D analogs have shown their efficacy in solid organ transplantation. The purpose of this study was to investigate the suitability of a novel vitamin D analog, MC1288, in the prevention of acute GVHD in a rat BMT model. Allogeneic BMT were performed from Lewis to BN rats (n = 18). The animals were divided into four groups: an untreated control group, MC1288, cyclosporin A (CsA), and MC1288 + CsA-treated groups. Rats were harvested for histology and immunohistochemistry on day 20 after BMT. Histological changes for GVHD in liver, skin, and spleen were scored. Positivity in immunostaining was quantified as the number of positive cells/high power field. Treatment with MC1288 decreased clinical signs of GVHD compared with untreated or CsA-treated rats. Histological manifestations of GVHD, expressed as mean total increment, were significantly lower (1.4 +/- 0.5) in MC1288 than in untreated (5.0 +/- 1.6) or CsA (3.5 +/- 1.0) groups. Combining MC1288 and CsA further improved histology (1.1 +/- 0.6). The expression of CD4, CD8, MHC class II, interleukin-2 receptor, nitric oxide 2, and NKR-P1A (NK cells) positivity was significantly decreased in the liver and skin of BMT rats by MC1288. MC1288 was effective in preventing clinical and histological signs and symptoms of GVHD. This novel vitamin D analog could be used as an immunomodulating agent in BMT.

  5. CT-analysis of the course of gastrointestinal graft-versus-host disease-Patterns of involvement

    Energy Technology Data Exchange (ETDEWEB)

    Ketelsen, D., E-mail: dominik.ketelsen@med.uni-tuebingen.de [Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Vogel, W.; Bethge, W.; Faul, C. [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Claussen, C.D.; Horger, M. [Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)

    2011-07-15

    Objective: To describe the main patterns of distribution of gastrointestinal graft-versus-host disease (GVHD) and their chronological course. Methods: Twenty-five adult patients (17 men, 8 women, mean age 47 years) were enrolled from 11/2003 to 11/2007. All patients underwent abdominopelvic CT shortly after onset of GVHD-related symptoms and also at follow up. The mean number of CT examinations per patient was 3.2 {+-} 2.7 with a total of 81 in a median time period of 97 days after HCT. The gastrointestinal tract was divided into 7 segments. Gastrointestinal abnormalities were defined as follows: presence of wall thickening (>4 mm), increased mucosal enhancement, bowel dilatation (>3 cm for the small bowel, >8 cm for the colon), fluid-filled loops of the bowel, bowel loop separation and double-halo sign. Results: 40% (10/25) of the patients presented a classical pattern of evolution of involved segments by GI-GVHD. In these cases, especially the small bowel was initially involved showing a retreat with time towards the terminal ileum with longer length of stay in this location. 28% (7/25) of the patients presented with a nonclassical permanently migratory involvement of the GI jumping from one GI segment to another. Other 32% (8/25) of our patients revealed a nonclassical persistent, unchanged involvement pattern of GI involvement by GVHD at time. Conclusion: Contrary to existing reports, our data collected in 25 patients diagnosed with GI-GVHD after allogeneic hematopoietic stem cell transplantation suggest the presence of three different courses (classical, nonclassical migratory and nonclassical persistent) of this disorder. Awareness of this knowledge enables more accurate risk stratification.

  6. Colonoscopy in the diagnosis of intestinal graft versus host disease and cytomegalovirus enteritis following allogeneic haematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    HE Jin-de; LIU Yu-lan; WANG Zhi-feng; LIU Dai-hong; CHEN Huan; CHEN Yu-hong

    2008-01-01

    Background Gastrointestinal graft versus host disease (GI-GVHD) and cytomegalovirus (CMV) enteritis are important complications following allogeneic haematopoietic stem cell transplantation (alIo-HSCT). We explored the role of colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following alIo-HSCT to identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made.Methods A retrospective analysis of the colonoscopic manifestations of GI-GVHD, CMV enteritis and GI-GVHD with concurrent CMV enteritis (GconC) and their related clinical issues.Results Forty-seven patients underwent 50 colonoscopies with diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy. Tortoise shell like changes of the mucosa (12 of 32) and deep ulcers (2 of 7) were specific endoscopic manifestations for GI-GVHD and CMV enteritis, respectively, while mucosal oedema, erythema, congestion, erosion and shallow ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC patients were prone to have oozing bleeding of the end ileal mucosa and typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC, 64%, 70% and 44% were taken from the rectum and sigmoid colon respectively.Conclusions Following alIo-HSCT, tortoise shell like changes and deep ulcers of the colonic mucosa are characteristic changes for Gl-GVHD and CMV enteritis, respectively, while the other lesions are not. Most of the GI-GVHDs and CMV enteritis cases can be diagnosed by left colon examination and tissue biopsy, but total colon examination to the terminal ileum is preferred.

  7. Correlation of lung abnormalities on high-resolution CT with clinical graft-versus-host disease after allogeneic versus autologous bone marrow transplantation in children

    Energy Technology Data Exchange (ETDEWEB)

    Merlini, Laura; Borzani, Irene Maria Olivia; Anooshiravani, Mehrak; Hanquinet, Sylviane [University of Geneva Children' s Hospital, Paediatric Radiology Unit, Geneva (Switzerland); Rochat, Isabelle [University of Geneva Children' s Hospital, Paediatric Pneumology Unit, Geneva (Switzerland); Ozsahin, Ayse Hulya [University of Geneva Children' s Hospital, Paediatric Oncology Unit, Geneva (Switzerland)

    2008-11-15

    Late-onset noninfectious pulmonary complications (LONIPCs) are life-threatening complications of bone marrow transplantation (BMT). Several pathological patterns are described in the literature with different prognoses, and with different relationships to graft-versus-host disease (GVHD). The role of high-resolution CT (HRCT) is not yet well established. To illustrate different patterns of LONIPCs on HRCT in allogeneic versus autologous BMT in order to investigate the correlation with chronic GVHD (cGVHD). A total of 67 HRCT scans were performed in 24 patients with noninfectious pulmonary disease at least 3 months after BMT (16 allogeneic, 8 autologous). Abnormality patterns and extension on HRCT images were correlated with the clinical outcome and with the severity of cGVHD. Of 24 patients, 9 showed LONIPCs (1 autologous, 8 allogeneic). There was a significant association between abnormalities on HRCT and severe cGVHD (P = 0.038), with no specific pattern. Prognosis seemed to be related to the severity of cGVHD and not to the extent of abnormalities on HRCT. The significant association between abnormalities on HRCT and severe GVHD suggests that LONIPCs can be a pulmonary manifestation of the disease. HRCT is a useful tool when combined with clinical data. (orig.)

  8. Factors Predicting Graft-versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Hematopoietic Cell Transplantation: Multivariable Analysis from a Single Center.

    Science.gov (United States)

    Solh, Melhem; Zhang, Xu; Connor, Katelin; Brown, Stacey; Solomon, Scott R; Morris, Lawrence E; Holland, H Kent; Bashey, Asad

    2016-08-01

    The ideal outcome of allogeneic hematopoietic cell transplantation (allo-HCT) is based on survival that is free of morbidity. The most common causes of treatment failure and morbidity after HCT are relapse, graft-versus-host disease (GVHD), and nonrelapse death. A composite endpoint that measures survival free of clinically significant negative events may be a useful way to determine the success of allo-HCT. We assessed GVHD and relapse-free survival (GRFS) where the events were acute GVHD grades III to IV, chronic GVHD requiring immunosuppression, relapse, or death in 531 consecutive adult patients who received an allo-HCT between 2006 and 2014 at our center. Median follow-up of living patients was 46 months (range, 12 to 123). HLA matched related donor (MRD, n = 198, 37%), matched unrelated donor (MUD, n = 205, 39%), and haploidentical donor with post-transplant cyclophosphamide (HID, n = 128, 24%) were used. Thirty-six percent of patients had a high/very-high Dana Farber disease risk index (DRI). Estimated rates of GRFS at 1 and 2 years after MRD, MUD, and HID transplantations were 34% and 26%, 26% and 17%, and 33% and 31%, respectively, with MRD recipients having a better GRFS than MUD (P disease risk, stem cell source, and donor type. Importantly, MUDs produce inferior GRFS to MRDs, whereas HIDs do not. PMID:27095692

  9. GVHD (Graft-Versus-Host Disease): A Guide for Patients and Families After Stem Cell Transplant

    Science.gov (United States)

    ... Disease): A guide for patients and families after stem cell transplant The immune system is the body's tool ... and attacking them. When you receive a donor's stem cells (the “graft”), the stem cells recreate the donor's ...

  10. Graft versus host disease in the bone marrow, liver and thymus humanized mouse model.

    Directory of Open Access Journals (Sweden)

    Matthew B Greenblatt

    Full Text Available Mice bearing a "humanized" immune system are valuable tools to experimentally manipulate human cells in vivo and facilitate disease models not normally possible in laboratory animals. Here we describe a form of GVHD that develops in NOD/SCID mice reconstituted with human fetal bone marrow, liver and thymus (NS BLT mice. The skin, lungs, gastrointestinal tract and parotid glands are affected with progressive inflammation and sclerosis. Although all mice showed involvement of at least one organ site, the incidence of overt clinical disease was approximately 35% by 22 weeks after reconstitution. The use of hosts lacking the IL2 common gamma chain (NOD/SCID/γc(-/- delayed the onset of disease, but ultimately did not affect incidence. Genetic analysis revealed that particular donor HLA class I alleles influenced the risk for the development of GVHD. At a cellular level, GVHD is associated with the infiltration of human CD4+ T cells into the skin and a shift towards Th1 cytokine production. GVHD also induced a mixed M1/M2 polarization phenotype in a dermal murine CD11b+, MHC class II+ macrophage population. The presence of xenogenic GVHD in BLT mice both presents a major obstacle in the use of humanized mice and an opportunity to conduct preclinical studies on GVHD in a humanized model.

  11. Kinetics of lymphocyte reconstitution after allogeneic bone marrow transplantation: markers of graft-versus-host disease.

    Science.gov (United States)

    Zinöcker, Severin; Sviland, Lisbet; Dressel, Ralf; Rolstad, Bent

    2011-07-01

    GVHD causes extensive morbidity and mortality in patients who receive alloHCT. Predictive and reliable markers for GVHD are currently lacking but required to improve the safety and accessibility of alloHCT. We present an experimental rat model of myeloablative total body irradiation and fully mismatched major and minor histoincompatible, T cell-depleted BMT, followed by delayed infusion of donor lymphocytes. This treatment, in contrast to marrow transplantation alone, resulted in severe aGVHD and 100% lethality within 2-6 weeks. We investigated the reconstitution kinetics and phenotypes of donor leukocyte subpopulations as well as the histopathology of selected organs that may correlate with GVHD, with the goal to find potential disease-related markers. We observed histological changes mainly confined to the skin, with degenerative changes in the basal layer. LNs and spleen showed deranged architecture with markedly increased accumulation of lymphocytes, whereas the gut, liver, and lungs appeared normal. Of the lymphocyte markers tested, donor-derived CD62L(+) T cells were markedly decreased in animals suffering from GVHD. Furthermore, we observed peripheral depletion of CD4(+)CD25(hi)FoxP3(+) T(reg), which was in contrast to controls. The relative frequency of these lymphocyte subpopulations in blood may therefore serve as accessible cellular markers of aGVHD. We propose that the animal model presented is instructive for the identification of clinically relevant markers of GVHD, which could improve disease diagnosis and management in alloHCT.

  12. Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Sydney X Lu

    Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

  13. B7H1/CD80 interaction augments PD-1-dependent T cell apoptosis and ameliorates graft versus host disease

    Science.gov (United States)

    Deng, Ruishu; Cassady, Kaniel; Li, Xiaofan; Yao, Sheng; Zhang, Mingfeng; Racine, Jeremy; Lin, Jeffrey; Chen, Lieping; Zeng, Defu

    2014-01-01

    Interactions of B7H1 (PD-L1) with its two ligands, PD-1 and CD80, on T cells play a pivotal role in controlling T cell activation, proliferation, anergy, and apoptosis. However, the interactions between the two pathways remain unknown. Using an alloimmune response model of graft-versus-host disease (GVHD), we report here that: 1) Comparison of proliferation and apoptosis of wild-type (WT) and PD-1−/− CD4+ conventional T (Tcon) cells in WT and B7H1−/− recipients has revealed that B7H1/CD80 interaction per se augments T cell proliferation, and this interaction augments T cell apoptosis mediated by B7H1/PD-1 interaction. This observation was recapitulated in an in vitro mixed lymphocyte reaction assay. 2) Specific blockade of the B7H1/CD80 axis by anti-B7H1 mAb reduces WT-alloreactive Tcon cell proliferation, IL-2 production, expression of PD-1, and apoptosis, resulting in worsening GVHD. In contrast, specific blockade of B7H1/CD80 interaction reduces donor PD-1−/− Tcon cell proliferation without impact on apoptosis, resulting in ameliorating GVHD. 3) B7H1 fused to an immunoglobulin Fc domain (B7H1-Ig), when produced in vivo by hydrodynamic injection of B7H1-Ig plasmid, ameliorates GVHD by augmenting proliferation and apoptosis of WT- alloreactive Tcon cells. Conversely, B7H1-Ig treatment has no impact on apoptosis but augments PD-1−/− T cell proliferation and worsens GVHD. These results indicate that B7H1/CD80 interaction augments Tcon cell proliferation, IL-2 production, and expression of PD-1, which leads to increased apoptosis mediated by the B7H1/PD1 pathway. Additionally, by engaging both PD-1 and CD80, B7H1-Ig can be a powerful therapeutic reagent for down-regulating the T cell immune response. PMID:25488990

  14. CTL-Promoting Effects of IL-21 Counteract Murine Lupus in the Parent→F1 Graft-versus-Host Disease Model.

    Science.gov (United States)

    Nguyen, Vinh; Rus, Horea; Chen, Ching; Rus, Violeta

    2016-02-15

    IL-21 promotes B cell and CTL responses in vivo, conferring IL-21 with a role in both humoral and cellular responses. Because CTL can target and eliminate autoreactive B cells, we investigated whether IL-21R signaling in CD8 T cells would alter the expansion of autoreactive B cells in an autoimmune setting. We addressed this question using the parent→F1 murine model of acute and chronic (lupus-like) graft-versus-host disease (GVHD) as models of a CTL-mediated or T-dependent B cell-mediated response, respectively. Induction of acute GVHD using IL-21R-deficient donor T cells resulted in decreased peak donor CD8 T cell numbers and decreased CTL effector function due to impaired granzyme B/perforin and Fas/Fas ligand pathways and a phenotype of low-intensity chronic GVHD with persistent host B cells, autoantibody production, and mild lupus-like renal disease. CTL effector maturation was critically dependent on IL-21R signaling in Ag-specific donor CD8, but not CD4, T cells. Conversely, treatment of DBA/2J→F1 chronic GVHD mice with IL-21 strongly promoted donor CD8 T cell expansion and rescued defective donor anti-host CTLs, resulting in host B cell elimination, decreased autoantibody levels, and attenuated renal disease, despite evidence of concurrently enhanced CD4 help for B cells and heightened B cell activation. These results demonstrate that, in the setting of lupus-like CD4 T cell-driven B cell hyperactivity, IL-21 signaling on Ag-specific donor CD8 T cells is critical for CTL effector maturation, whereas a lack of IL-21R downregulates CTL responses that would otherwise limit B cell hyperactivity and autoantibody production. PMID:26792801

  15. Ferritin concentrations correlate to outcome of hematopoietic stem cell transplantation but do not serve as biomarker of graft-versus-host disease.

    Science.gov (United States)

    Großekatthöfer, M; Güclü, E D; Lawitschka, A; Matthes-Martin, S; Mann, G; Minkov, M; Peters, C; Seidel, M G

    2013-08-01

    Clinical presentation and laboratory data are often too unspecific to distinguish the onset or activity of graft-versus-host disease (GvHD) from infections or toxicity. Antigen-presenting cells such as monocytes/macrophages and dendritic cells are involved in GvHD pathogenesis after allogeneic hematopoietic stem cell transplantation (HSCT). To test whether ferritin, an iron storage marker and macrophage activation-linked acute-phase protein, represents a candidate biomarker for acute or chronic GvHD in pediatric HSCT, we retrospectively evaluated a 2-year follow-up data from 131 eligible consecutive patients with different malignant and nonmalignant diseases who underwent allogeneic HSCT. Thirteen patients (10 %) suffered from acute GvHD II-IV°, 18 (14 %) had limited, and 14 (11 %) had extensive chronic GvHD. In extension of previous studies in adults investigating pre-transplant ferritin, our data show that post-HSCT hyperferritinemia (analyzed on days 0, +30, +60, +100, +180, +360, and +720) was significantly associated with decreased long-term survival (p children and adolescents. Increased ferritin concentrations were associated with number and timing of red blood cell transfusions and toxic or infectious multi-organ failure but did not show significant differences between patients without GvHD and with acute grades II-IV, limited, or extensive chronic GvHD. Thus, our data do not identify ferritin as specifically GvHD-linked biomarker; however, they support the prognostic value of ferritin levels for outcome after HSCT in children.

  16. The Use of Hyperbaric Oxygen Therapy in the Treatment of Non-healing Ulcers Secondary to Graft-versus-host Disease

    OpenAIRE

    Heyboer, Marvin; Taylor, Justin; Morgan, Monica; Mariani, Peter; Jennings, Shane

    2014-01-01

    We present the case of a 69 year-old gentleman with non-healing ulcers of the bilateral medial malleoli as a result of graft-versus-host disease (GvHD). The patient discussed was diagnosed with stage IV mantle cell lymphoma. Over the course of 4 years the patient was treated with autologous stem cell transplant, later reduced-intensity allogeneic stem cell transplant, and finally donor lymphocyte infusion due to recurrence. Following these therapies, the patient developed extensive GvHD that ...

  17. Immunobiology of the graft-versus-host reaction. I. Symptons of graft-versus-host disease in mice are preceded by delayed-type hypersensitivity to host histocompatibility antigens

    International Nuclear Information System (INIS)

    During initiation of an acute graft-versus-host reaction by injection of C57BL/Rij spleen cells into lethally irradiated (C57BL/Rij x CBA/Rij)F1 hybrid mice, a state of delayed-type hypersensitivity (DTH) against host histocompatibility (H) antigens occurs. This was demonstrated by means of transfer of host spleen and lymph node cells into C57BL/Rij recipients, which received a challenge with CBA/Rij spleen cells. Initiation and transfer of the graft-versus-host-related DTH reactivity was highly dependent on Thy-1.2+ cells. The development of DTH reactivity started between 8 and 24 hr after semiallogeneic spleen cell transplantation and increased during the days thereafter. In the spleen maximum DTH reactivity was found on day 4, whereas in the lymph nodes maximal reactivity occurred on day 5 after irradiation and reconstitution. Thereafter, the reactivity decreased until there was no further DTH reactivity--demonstrable on day 13. The specificity of the DTH reactivity for host H antigens was proved by no reactivity to a challenge of DBA/2 and Swiss spleen cells, which are H-2-incompatible with CBA cells

  18. Effect and mechanism of acute graft versus host disease on early diffuse murine lung injury following allogeneic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/6→BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor α (TNFα) and Interferon (IFNγ) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFα were lower on day +7 than on day +3. In group B, the levels of TNFα attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFα were highest on day

  19. Heterogeneity in Studies of Mesenchymal Stromal Cells to Treat or Prevent Graft-versus-Host Disease: A Scoping Review of the Evidence.

    Science.gov (United States)

    Rizk, Mina; Monaghan, Madeline; Shorr, Risa; Kekre, Natasha; Bredeson, Christopher N; Allan, David S

    2016-08-01

    Effective treatments are lacking for the treatment of steroid-refractory graft-versus-host disease (GVHD), a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Mesenchymal stromal cells (MSCs) have demonstrated promise but there is uncertainty regarding their clinical effectiveness. A systematic scoping review of the literature was performed to characterize the heterogeneity of published studies and identify opportunities for standardization. Thirty studies were identified, including 19 studies (507 patients) addressing the treatment of acute or chronic GVHD and 11 prevention studies (277 patients). Significant heterogeneity was observed in the age and diagnoses of study subjects, intensity and specifics of the conditioning regimens, degree of HLA matching, and source of hematopoietic cells. MSCs were derived from bone marrow (83% of studies), cord blood (13%), or adipose tissue (3%) and were cryopreserved from third-party allogeneic donors in the majority of studies (91% of prevention studies and 63% of treatment studies). Culture conditions and media supplements were highly variable and characterization of MSCs did not conform to all International Society for Cellular Therapy criteria in any study. MSCs were harvested from cell culture at passage 1 to 7 and the dosage of MSCs ranged from 0.3 to 10 × 10(6)/kg, using varying schedules of administration. Treatment response criteria were not standardized and effectiveness in controlled treatment studies (5 studies) was unconvincing. Details of actively recruiting trials suggest heterogeneity still persists with only 53% of registered trials describing the use of standard GVHD response criteria and few detailing methods of MSC manufacturing. Future studies will need to make substantial coordinated efforts to reduce study heterogeneity and clarify the role of MSCs in GVHD. PMID:27130504

  20. Skin manifestations and treatment of graft-versus-host disease%移植物抗宿主病的皮肤表现及治疗进展

    Institute of Scientific and Technical Information of China (English)

    惠云; 胡文星; 陈军; 刘娟; 邓德权; 孔庆涛; 桑红

    2015-01-01

    Graft-versus-host disease (GVHD) is an autoimmune disease caused by graft-versus-host reaction,occurring most frequently in patients receiving allogeneic hematopoietic stem cell transplantation and occasionally in patients receiving organ transplantation.It often involves multiple organ systems,of which,skin and mucous membranes are the most frequently affected system with various clinical manifestations.Acute GVHD often appears as measles-or scarlet fever-like skin rashes with severe systemic symptoms such as fever and poor appetite,and may rapidly progress into toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (SJS) in a few days.Lichen planus and sclerodermoid lesions are the most common clinical manifestations of chronic GVHD.With further understanding of this disease in recent years,some new manifestations have been observed,such as psoriasis-and atopic dermatitis-like skin lesions,as well as nail changes in some cases.It is especially important to select appropriate treatment protocols according to clinical manifestations.Glucocorticoids combined with immunosuppressive agents are a conventional treatment for GVHD,and innovative treatments have emerged with the development of therapeutics.%移植物抗宿主病是由移植物抗宿主反应所引起的一种免疫性疾病,好发于同种异体造血干细胞移植的患者,少数发生于器官移植后的患者.常累及全身多个器官,皮肤黏膜最常受累且临床表现多样.急性移植物抗宿主病常出现麻疹样及猩红热样的皮肤改变,发热、食欲不振等全身不适症状较重,且皮疹进展较快,数日内可出现中毒性表皮坏死松解症或Stevens-Johnson综合征等皮肤改变,而扁平苔藓及硬皮病样的皮损为慢性移植物抗宿主病最常见的皮肤表现.随着近年来对该病的认识,发现了较多新症状,如银屑病样、特应性皮炎样的皮疹,部分还会出现甲改变等症状.针对不同的临床表现选择合适的治疗

  1. Immunosuppression for 6-8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant

    Institute of Scientific and Technical Information of China (English)

    Yan Chenhua; Xu Lanping; Liu Daihong; Chen Huan; Wang Yu; Liu Kaiyan; Huang Xiaojun

    2014-01-01

    Background In haploidentical hematopoietic stem cell transplantation (HSCT),the duration of graft-versus-host disease (GVHD) prophylaxis after modified donor lymphocyte infusion (DLI) was the only risk factor of DLI-associated grades 3-4 acute GVHD.However,the successful application of modified DLI depended not only on the reduction of severe GVHD,but also on the preservation of graft-versus-leukemia (GVL) effect.Therefore,this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for <6 weeks on GVL effect after modified DLI in haploidentical HSCT.Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease (MRD)-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively.Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for <6 weeks.Results First,compared with prophylaxis for <6 weeks,prophylaxis for 6-8 weeks reduced incidence of relapse in total patients (26.6% vs.69.0%,P <0.001).Besides,prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant (P=0.018) and in 49 patients developing MRD-positive status post-transplant (P <0.001).Second,prophylaxis for 6-8 weeks reduced incidence of acute GVHD (P <0.05),reduced the therapeutic application of immunosuppressive agents (P=0.019),but increased the incidence of chronic GVHD (P<0.05).Third,prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients,as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant (P <0.05).Conclusions In haploidentical HSCT,prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect,but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for <6 weeks.This strategy will

  2. Cyclosporine Plus Methotrexate or Cyclosporine Plus Mycophenolate Mofetil as Graft Versus Host Disease Prophylaxis in Acute Leukemia Transplant: Comparison of Toxicity, Engraftment Kinetics and Transplant Outcome.

    Science.gov (United States)

    Gupta, Alok; Punatar, Sachin; Mathew, Libin; Kannan, Sadhana; Khattry, Navin

    2016-09-01

    We sought to compare two graft-versus-host disease (GVHD) prophylaxis regimen, cyclosporine and methotrexate (CsA+MTX) with CsA+mycophenolate mofetil (MMF) in 77 acute leukemia patients who underwent hematopoietic stem cell transplant (HSCT) between January 2008 and March 2013. Fifty-three patients received CsA+MTX while 24 received CsA+MMF. The incidence of grade 3-4 mucositis and grade 3-4 diarrhea was 74 and 6 % with CsA+MTX compared to 33 % and 21 % with CsA+MMF (P = 0.001 and 0.09 respectively). Forty-two (79 %) patients in CsA+MTX group required total parenteral nutrition compared to 14 (58 %) in CsA+MMF group (P = 0.09). The incidence of engraftment fever was 17 % with CsA+MTX and 41 % with CsA+MMF (P = 0.02). The median time to neutrophil and platelet engraftment was 14 days and 13 days with CsA+MTX compared to 12 days and 10 days with CsA+MMF (P = 0.003 and 0.08 respectively). The incidence of any grade and grade II-IV acute GVHD was 45 and 13 % with CsA+MTX compared to 42 and 29 % with CsA+MMF (P = NS). Incidence of overall and extensive chronic GVHD was 57 and 38 % with CsA+MTX compared to 42 and 17 % with CsA+MMF (P = NS). Incidence of relapse was 38 % with CsA+MTX compared to 33 % with CsA+MMF (P = NS). TRM was 6 % with CsA+MTX and 21 % with CsA+MMF (P = NS). At 2 years, overall survival (OS) was 64 % in CsA+MTX group compared to 46 % in CsA+MMF group (P = NS). We conclude that CsA+MMF is associated with lesser toxicity, faster myeloid engraftment and similar rates of acute and chronic GVHD, TRM, relapse and OS compared to CsA+MTX in acute leukemia transplant. PMID:27429515

  3. Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

    Directory of Open Access Journals (Sweden)

    Ana Verena Almeida Mendes

    2008-01-01

    Full Text Available OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05. A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94%, p<0.01 and an increase in CD57+ lymphocytes (5.60%, p<0.01. This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant, also had an impact on the CD57+ subset, triggering an increase of 4.9% in CD57+ lymphocytes (p<0.05. CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

  4. Reduced graft-versus-host disease-inducing capacity of T cells after activation, culturing, and magnetic cell sorting selection in an allogeneic bone marrow transplantation model in rats

    NARCIS (Netherlands)

    Weijtens, M; van Spronsen, A; Hagenbeek, A; Braakman, E; Martens, A

    2002-01-01

    Graft-versus-host disease (GvHD), a major complication of allogeneic bone marrow transplantation, has been ascribed to mature T cells in the graft. Because T cells play an important role in engraftment of the bone marrow and decrease the probability of relapse of leukemia, a treatment strategy was d

  5. Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial

    NARCIS (Netherlands)

    Choi, S.W.; Braun, T.; Chang, L.; Ferrara, J.L.; Pawarode, A.; Magenau, J.M.; Hou, G.; Beumer, J.H.; Levine, J.E.; Goldstein, S.; Couriel, D.R.; Stockerl-Goldstein, K.; Krijanovski, O.I.; Kitko, C.; Yanik, G.A.; Lehmann, M.H.; Tawara, I.; Sun, Y; Paczesny, S.; Mapara, M.Y.; Dinarello, C.A.; Dipersio, J.F.; Reddy, P.

    2014-01-01

    BACKGROUND: Acute graft-versus-host disease (GVHD) remains a barrier to more widespread application of allogeneic haemopoietic stem-cell transplantation. Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models. We aimed to study the safety and activit

  6. Establishment of a Murine Model of Chronic Graft-Versus-Host Disease After Minor Histocompatibility Antigen Mismatched Bone Marrow Transplantation%miHA不合异基因骨髓移植后慢性移植物抗宿主病小鼠模型的建立

    Institute of Scientific and Technical Information of China (English)

    黄欣; 翁建宇; 吴萍; 童嘉琦; 杜欣

    2014-01-01

    Objective To establish a murine model of chronic graft-versus-host disease (cGVHD) after major histocompatibility complex (MHC) matched and minor histocompatibility antigen (miHA) mismatched allogeneic bone marrow transplantation,and to provide in vivo research tools for cGVHD.Methods 20 recipients BALB/c (H2d) female mice were included in this study.They were divided into blank control group (n =5),irradiation control group (n =5),transplantation group (n =5) and the cGVHD group (n=5).In addition to the blank control group,the rest of the three groups of mice were irradiated with 700 cGy dose of linear accelerator.Then the irradiation control group were injected with 0.2 ml PPMI 1640; the trarsplantation group were injected with 8 × 106 bone-marrow cells,and cGVHD group were injected with bone-marrow cells and spleen cells (8× 106,1 ∶ 1) from B10.D2(Hc1 H2d H2-T18c) male mice.The observed items post-transplantation included hematopoietic reconstruction,implant,and general condition.Clinical scores were assessed every 3 days after +14 d.At + 50 d,mice were put to death for evaluation target organ pathological changes.Animal Intervention met animal ethical standard.Results Mice in transplantation groups were in hematopoietic reconstruction at +7 d,and all survived to the end point (+ 50 d).Chromosomes of recipient mice were in donor form.Clinical scores of cGVHD group have been more than 0.6 since +20 d.Pathological changes of skin,liver and lung were obviously,and pathological scores were significant higher than those of transplantation control groups (F=88.02,P< 0.05).Conclusions Irradiation dose for 700 cGy,8× 106 of bone marrow and spleen cell number infusion induce a successful cGVHD murine model,which might be an ideal study model of clinical cGVHD after bone marrow transplantation.%目的 通过主要组织相容性复合物(MHC)相合,次要组织相容性抗原(miHA)不合的异基因骨髓移植,建立慢性移植物抗宿主病(cGVHD)小鼠模型,

  7. Mesenchymal stromal cells from pooled mononuclear cells of multiple bone marrow donors as rescue therapy in pediatric severe steroid-refractory graft-versus-host disease: a multicenter survey.

    Science.gov (United States)

    Kuçi, Zyrafete; Bönig, Halvard; Kreyenberg, Hermann; Bunos, Milica; Jauch, Anna; Janssen, Johannes W G; Škifić, Marijana; Michel, Kristina; Eising, Ben; Lucchini, Giovanna; Bakhtiar, Shahrzad; Greil, Johann; Lang, Peter; Basu, Oliver; von Luettichau, Irene; Schulz, Ansgar; Sykora, Karl-Walter; Jarisch, Andrea; Soerensen, Jan; Salzmann-Manrique, Emilia; Seifried, Erhard; Klingebiel, Thomas; Bader, Peter; Kuçi, Selim

    2016-08-01

    To circumvent donor-to-donor heterogeneity which may lead to inconsistent results after treatment of acute graft-versus-host disease with mesenchymal stromal cells generated from single donors we developed a novel approach by generating these cells from pooled bone marrow mononuclear cells of 8 healthy "3(rd)-party" donors. Generated cells were frozen in 209 vials and designated as mesenchymal stromal cell bank. These vials served as a source for generation of clinical grade mesenchymal stromal cell end-products, which exhibited typical mesenchymal stromal cell phenotype, trilineage differentiation potential and at later passages expressed replicative senescence-related markers (p21 and p16). Genetic analysis demonstrated their genomic stability (normal karyotype and a diploid pattern). Importantly, clinical end-products exerted a significantly higher allosuppressive potential than the mean allosuppressive potential of mesenchymal stromal cells generated from the same donors individually. Administration of 81 mesenchymal stromal cell end-products to 26 patients with severe steroid-resistant acute graft-versus-host disease in 7 stem cell transplant centers who were refractory to many lines of treatment, induced a 77% overall response at the primary end point (day 28). Remarkably, although the cohort of patients was highly challenging (96% grade III/IV and only 4% grade II graft-versus-host disease), after treatment with mesenchymal stromal cell end-products the overall survival rate at two years follow up was 71±11% for the entire patient cohort, compared to 51.4±9.0% in graft-versus-host disease clinical studies, in which mesenchymal stromal cells were derived from single donors. Mesenchymal stromal cell end-products may, therefore, provide a novel therapeutic tool for the effective treatment of severe acute graft-versus-host disease. PMID:27175026

  8. Mesenchymal stromal cells from pooled mononuclear cells of multiple bone marrow donors as rescue therapy in pediatric severe steroid-refractory graft-versus-host disease: a multicenter survey

    Science.gov (United States)

    Kuçi, Zyrafete; Bönig, Halvard; Kreyenberg, Hermann; Bunos, Milica; Jauch, Anna; Janssen, Johannes W.G.; Škifić, Marijana; Michel, Kristina; Eising, Ben; Lucchini, Giovanna; Bakhtiar, Shahrzad; Greil, Johann; Lang, Peter; Basu, Oliver; von Luettichau, Irene; Schulz, Ansgar; Sykora, Karl-Walter; Jarisch, Andrea; Soerensen, Jan; Salzmann-Manrique, Emilia; Seifried, Erhard; Klingebiel, Thomas; Bader, Peter; Kuçi, Selim

    2016-01-01

    To circumvent donor-to-donor heterogeneity which may lead to inconsistent results after treatment of acute graft-versus-host disease with mesenchymal stromal cells generated from single donors we developed a novel approach by generating these cells from pooled bone marrow mononuclear cells of 8 healthy “3rd-party” donors. Generated cells were frozen in 209 vials and designated as mesenchymal stromal cell bank. These vials served as a source for generation of clinical grade mesenchymal stromal cell end-products, which exhibited typical mesenchymal stromal cell phenotype, trilineage differentiation potential and at later passages expressed replicative senescence-related markers (p21 and p16). Genetic analysis demonstrated their genomic stability (normal karyotype and a diploid pattern). Importantly, clinical end-products exerted a significantly higher allosuppressive potential than the mean allosuppressive potential of mesenchymal stromal cells generated from the same donors individually. Administration of 81 mesenchymal stromal cell end-products to 26 patients with severe steroid-resistant acute graft-versus-host disease in 7 stem cell transplant centers who were refractory to many lines of treatment, induced a 77% overall response at the primary end point (day 28). Remarkably, although the cohort of patients was highly challenging (96% grade III/IV and only 4% grade II graft-versus-host disease), after treatment with mesenchymal stromal cell end-products the overall survival rate at two years follow up was 71±11% for the entire patient cohort, compared to 51.4±9.0% in graft-versus-host disease clinical studies, in which mesenchymal stromal cells were derived from single donors. Mesenchymal stromal cell end-products may, therefore, provide a novel therapeutic tool for the effective treatment of severe acute graft-versus-host disease. PMID:27175026

  9. TGF-β-induced CD4+Foxp3+ T cells attenuate acute graft-versus-host disease by suppressing expansion and killing of effector CD8+ cells.

    Science.gov (United States)

    Gu, Jian; Lu, Ling; Chen, Maogen; Xu, Lili; Lan, Qin; Li, Qiang; Liu, Zhongmin; Chen, Guihua; Wang, Ping; Wang, Xuehao; Brand, David; Olsen, Nancy; Zheng, Song Guo

    2014-10-01

    The use of TGF-β-induced CD4(+)Foxp3(+) T cells (induced regulatory T cells [iTregs]) is an important prevention and treatment strategy in autoimmune diseases and other disorders. However, the potential use of iTregs as a treatment modality for acute graft-versus-host disease (aGVHD) has not been realized because they may be unstable and less suppressive in this disease. We restudied the ability of iTregs to prevent and treat aGVHD in two mouse models. Our results showed that, as long as an appropriate iTreg-generation protocol is used, these iTregs consistently displayed a potent ability to control aGVHD development and reduce mortality in the aGVHD animal models. iTreg infusion markedly suppressed the engraftment of donor CD8(+) cells and CD4(+) cells, the expression of granzyme A and B, the cytotoxic effect of donor CD8(+) cells, and the production of T cell cytokines in aGVHD. Therefore, we conclude that as long as the correct methods for generating iTregs are used, they can prevent and even treat aGVHD. PMID:25156367

  10. Ex vivo expansion of regulatory T cells for clinical applications against graft-versus-host disease in allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lan-fang; XIA Chang-qing

    2013-01-01

    Objective To review the characteristics of regulatory T cells (Tregs) and ex vivo expansion of Tregs for treatment of graftversus-host disease (GVHD).Data sources The data used in this review were retrieved from PubMed (1970-2013).The terms "ex vivo expansion","regulatory T cell",and "graft-versus-host disease" were used for literature search.Study selection The publications about the characteristics of Tregs,ex vivo expansion of Tregs and clinical applications of Tregs against GVHD were identified,retrieved and reviewed.Results Tregs can be classified as natural Tregs (nTregs) and induced Tregs (iTregs).Both subsets share most Treg features.Given their immunosuppressive property,Tregs have been tested for their capability of preventing GVHD.The bottleneck of Treg therapy is the limited numbers of naturally existing Tregs.To solve this problem,ex vivo expansion of nTregs or iTregs has been executed.The initial data indicate Treg therapy is effective in reducing GVHD without compromising graft-versus-leukemia (GVL).Conclusion Ex vivo expansion of Tregs is a reliable way to prepare sufficient number of Tregs for management of GVHD.

  11. Beclomethasone Dipropionate in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

    Science.gov (United States)

    2015-03-05

    Hematopoietic/Lymphoid Cancer; Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Graft Versus Host Disease; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Disease, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small

  12. Reduced IL-35 levels are associated with increased platelet aggregation and activation in patients with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Zhang, Xiaohui; Zhou, Yi; Xu, Lanping; Han, Wei; Chen, Huan; Chen, Yuhong; Fu, Haixia; Zhou, Shiyuan; Zhao, Jingzhong; Wang, Qianming; Feng, Feier; Zhu, Xiaolu; Liu, Kaiyan; Huang, Xiaojun

    2015-05-01

    Acute graft-versus-host disease (aGVHD) is a major complication associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that suppresses the immune response. This prospective study explored IL-35 plasma levels in 65 patients after HSCT. The results revealed that the peripheral blood of patients with grades III-IV aGVHD (23.46 ng/ml) had reduced IL-35 compared to transplanted patients with grades I-II aGVHD (40.26 ng/ml, p IL-35 levels with respect to aGVHD. The patients who received lower levels of IL-35 cells in the GBM (28.0 ng/ml, p = 0.551) or lower levels of IL-35 in PBPC (53.46 ng/ml, p = 0.03) exhibited a higher incidence of aGVHD. Patients with aGVHD have increased platelet aggregation. IL-35 was added to patient blood in vitro, and platelet aggregation was inhibited by IL-35 in a dose-dependent manner. The markers of platelet activation (CD62P/PAC-1) can also be inhibited by IL-35. The results indicate that IL-35 may affect the development of aGVHD by inhibiting platelet activation and aggregation. Our data suggests that IL-35 represents a potentially effective therapeutic agent against aGVHD after allo-HSCT.

  13. Effect of major histocompatibility complex haplotype matching by C4 and MICA genotyping on acute graft versus host disease in unrelated hematopoietic stem cell transplantation.

    Science.gov (United States)

    Park, Yongjung; Cheong, June-Won; Park, Myoung Hee; Kim, Myoung Soo; Kim, Jong Sun; Kim, Hyon-Suk

    2016-02-01

    We explored whether matching of human leukocyte antigen (HLA) haplotypes between the recipient and donor of hematopoietic stem cell transplantation (HSCT) predicted by C4 and MICA typing is associated with the incidence of acute graft versus host disease (aGVHD). DNA preparations collected from a total of 81 recipient and donor pairs were used for PCR-based C4 subtyping and/or MICA sequence-based typing. Incidences of aGVHD were compared according to C4 and MICA matching. The six most common MICA alleles were MICA*008:01, *010:01, *002:01, *004, *009:01/049, and *012:01. Among the 59 unrelated pairs, HLA alleles were matched in 34 (57.6%). C4 subtypes were identical between the recipient and donor in 28 (82.4%) HLA-matched unrelated pairs, while MICA genotypes were matched in all HLA-matched unrelated pairs. In the 22 HLA-matched related pairs, all recipients showed identical C4 subtypes with their respective donors. In multivariate analysis, C4 mismatch was a significant risk factor associated with the development of aGVHD in unrelated HSCT (hazard ratio=3.24, P=0.006). PCR-based C4 subtyping is a simple method for assessing the genetic identity of the HLA region between a recipient and unrelated donor. This test would be also useful for prediction of aGVHD in HSCT.

  14. Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

    International Nuclear Information System (INIS)

    Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients

  15. Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host Disease of the Intestine by Expansion of Regulatory T Cells

    Science.gov (United States)

    Iyama, Satoshi; Yoshida, Masahiro; Ibata, Soushi; Tatekoshi, Ayumi; Kamihara, Yusuke; Horiguchi, Hiroto; Murase, Kazuyuki; Kawano, Yutaka; Takada, Kohichi; Miyanishi, Koji; Kobune, Masayoshi; Ichimiya, Shingo; Kato, Junji

    2016-01-01

    Narrowband ultraviolet B (NB-UVB) has been widely used in dermatological phototherapy. As for the application of NB-UVB phototherapy to graft-versus-host disease (GVHD), we previously reported that it was highly efficacious for cutaneous lesions of acute GVHD (aGVHD) and that expansion of regulatory T (Treg) cells induced by NB-UVB might be one of the mechanisms. In order to examine whether NB-UVB irradiation through expansion of Treg cells is effective for the treatment of not only cutaneous aGVHD but also aGVHD of inner organs such as the intestine or liver, we conducted experiments in which a murine lethal aGVHD model, characterized by severe involvement of the intestine, was irradiated with NB-UVB. We found that NB-UVB irradiation improved the clinical score and survival rate. The pathological score of aGVHD was improved in all affected organs: intestine, liver, and skin. In the serum of mice irradiated with NB-UVB, the levels of Treg cells-associated cytokines such as transforming growth factor beta (TGFβ) and interleukin-10 (IL-10) were elevated. The numbers of infiltrating Treg cells in inflamed tissue of the intestine and those in spleen were increased in mice treated with NB-UVB. This is the first report demonstrating that NB-UVB phototherapy has the ability to ameliorate intestinal aGVHD through the expansion of Treg cells. PMID:27031239

  16. Pretransplant β2-Microglobulin Is Associated with the Risk of Acute Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplant.

    Science.gov (United States)

    Costa-Lima, Carolina; Miranda, Eliana Cristina Martins; Colella, Marcos Paulo; Aranha, Francisco Jose Penteado; de Souza, Carmino Antonio; Vigorito, Afonso Celso; De Paula, Erich Vinicius

    2016-07-01

    The risk of acute graft-versus-host disease (aGVHD) can be reliably estimated by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), which can be further refined by the incorporation of pre-hematopoietic cell transplantation (HCT) serum levels of inflammatory biomarkers such as ferritin and albumin. β2-Microglobulin (β2-m) is a key component of the MHC class I complex, which is independently associated with mortality and frailty in the general population. We took advantage of our institutional protocol that includes measurement of pre-HCT β2-m serum levels in the most patients to investigate whether pre-transplant β2-m levels were associated with the risk of aGVHD. One hundred three consecutive patients submitted to allogeneic HCT, of which 26 developed grades II to IV aGVHD, were included in the analysis. β2-m was significantly associated with age and HCT-CI. Higher levels of β2-m were observed in patients who developed aGVHD (P = .008). In the multivariate Cox regression model, β2-m and HCT-CI remained independently associated with the risk of developing aGVHD. In conclusion, the association between β2-m and the occurrence of aGVHD suggests that the measurement of this protein before HCT might represent an additional element for risk stratification of aGVHD. PMID:27044906

  17. The role of pattern-recognition receptors in Graft-versus-host disease and Graft-versus-leukemia after allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Simon eHeidegger

    2014-07-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (allo-HSCT is the only treatment with curative potential for certain aggressive hematopoietic malignancies. Its success is limited by acute graft-versus-host disease (GVHD, a life-threatening complication that occurs when alloreactive donor T cells attack recipient organs. There is growing evidence that microbes and innate pattern-recognition receptors (PRRs such as toll-like (TLR and nod-like receptors (NLR are critically involved in the pathogenesis of acute GVHD. A now widely accepted model postulates that intensive chemotherapy and / or total-body irradiation during pre-transplant conditioning result in tissue damage and a loss of epithelial barrier function. Subsequent translocation of bacterial components as well as release of endogenous danger molecules stimulate PRRs of host antigen-presenting cells (APCs to trigger the production of pro-inflammatory cytokines (‘cytokine storm’ that modulate T cell alloreactivity against host tissues, but eventually also the beneficial graft-versus-leukemia (GVL effect. Given the limitations of existing immunosuppressive therapies, a better understanding of the molecular mechanisms which govern GVHD vs GVL is urgently needed. This may ultimately allow to design modulators which protect from GvHD but preserve donor T-cell attack on hematologic malignancies. Here, we will briefly summarize current knowledge about the role of innate immunity in the pathogenesis of GVHD and GVL following allo-HSCT.

  18. Reduction of fatal graft-versus-host disease by 3H--thymidine suicide of donor cells cultured with host cells

    International Nuclear Information System (INIS)

    The effect of the tritiated thymidine (3H-TdR) suicide technique on the ability of donor cells to induce fatal graft-versus-host disease (GVHD) was studied. C57BL/6 (H-2/sup b/) spleen cells were stimulated in vitro with irradiated BALB/c (H-2/sup d/) Moloney lymphoma cells in mixed culture and 3H-TdR of high-specific activity added to eliminate proliferating cells. The ability of such cells to induce fatal GVHD was assayed by injecting them i.v. into adult BALB/c mice immunosuppressed with cyclophosphamide (180 mg/kg). These cells induced fatal GVHD in fewer mice (52 percent) than did C57BL/6 cells cultured with BALB/c lymphoma cells but without 3H-TdR (87 percent) and C57BL/6 cells cultured with irradiated C57BL/6 cells with (95 percent) or without 3H-TdR (86 percent). Thus, the 3H-TdR suicide technique greatly diminished the ability of cells to induce lethal GVHD

  19. Risk Factors for Steroid-Refractory Acute Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation from Matched Related or Unrelated Donors.

    Science.gov (United States)

    Calmettes, Claire; Vigouroux, Stéphane; Labopin, Myriam; Tabrizi, Reza; Turlure, Pascal; Lafarge, Xavier; Marit, Gérald; Pigneux, Arnaud; Leguay, Thibaut; Bouabdallah, Krimo; Dilhuydy, Marie-Sarah; Duclos, Cédric; Mohr, Catherine; Lascaux, Axelle; Dumas, Pierre-Yves; Dimicoli-Salazar, Sophie; Saint-Lézer, Arnaud; Milpied, Noël

    2015-05-01

    We performed a retrospective study to identify pretransplantation risk factors for steroid-refractory (SR) acute graft-versus host disease (aGVHD) after allogeneic stem cell transplantation from matched donors in 630 adult patients who underwent transplantation at our center between 2000 and 2012. The cumulative incidence (CI) of SR aGVHD was 11.3% ± 2.3%. The identified independent risk factors were matched unrelated donor (hazard ratio [HR], 2.52; P = .001), female donor for male recipient (HR, 1.84; P = .023) and absence of antithymocyte globulin (HR, 2.02; P = .005). Three risk groups were defined according to the presence of these risk factors. In the whole cohort, the CI of SR aGVHD was 3.5% ± 1.7% in the low-risk group (0 risk factor, n = 115), 9.3% ± 1.6% in the intermediate-risk group (1 risk factor, n = 323), and 19.3% ± 2.9% in the high-risk group (2 or 3 risk factors, n = 192). Our study suggests that pretransplantation characteristics might help identify patients at high risk for SR aGVHD. A risk adapted first-line treatment of aGVHD could be evaluated in those patients.

  20. Prevention of transfusion-associated graft-versus-host disease by irradiation: technical aspect of a new ferrous sulphate dosimetric system.

    Directory of Open Access Journals (Sweden)

    Lucas Sacchini Del Lama

    Full Text Available Irradiation of whole blood and blood components before transfusion is currently the only accepted method to prevent Transfusion-Associated Graft-Versus-Host-Disease (TA-GVHD. However, choosing the appropriate technique to determine the dosimetric parameters associated with blood irradiation remains an issue. We propose a dosimetric system based on the standard Fricke Xylenol Gel (FXG dosimeter and an appropriate phantom. The modified dosimeter was previously calibrated using a (60Co teletherapy unit and its validation was accomplished with a (137Cs blood irradiator. An ionization chamber, standard FXG, radiochromic film and thermoluminescent dosimeters (TLDs were used as reference dosimeters to determine the dose response and dose rate of the (60Co unit. The dose distributions in a blood irradiator were determined with the modified FXG, the radiochromic film, and measurements by TLD dosimeters. A linear response for absorbed doses up to 54 Gy was obtained with our system. Additionally, the dose rate uncertainties carried out with gel dosimetry were lower than 5% and differences lower than 4% were noted when the absorbed dose responses were compared with ionization chamber, film and TLDs.

  1. Prevention of transfusion-associated graft-versus-host disease by irradiation: technical aspect of a new ferrous sulphate dosimetric system.

    Science.gov (United States)

    Del Lama, Lucas Sacchini; de Góes, Evamberto Garcia; Petchevist, Paulo César Dias; Moretto, Edson Lara; Borges, José Carlos; Covas, Dimas Tadeu; de Almeida, Adelaide

    2013-01-01

    Irradiation of whole blood and blood components before transfusion is currently the only accepted method to prevent Transfusion-Associated Graft-Versus-Host-Disease (TA-GVHD). However, choosing the appropriate technique to determine the dosimetric parameters associated with blood irradiation remains an issue. We propose a dosimetric system based on the standard Fricke Xylenol Gel (FXG) dosimeter and an appropriate phantom. The modified dosimeter was previously calibrated using a (60)Co teletherapy unit and its validation was accomplished with a (137)Cs blood irradiator. An ionization chamber, standard FXG, radiochromic film and thermoluminescent dosimeters (TLDs) were used as reference dosimeters to determine the dose response and dose rate of the (60)Co unit. The dose distributions in a blood irradiator were determined with the modified FXG, the radiochromic film, and measurements by TLD dosimeters. A linear response for absorbed doses up to 54 Gy was obtained with our system. Additionally, the dose rate uncertainties carried out with gel dosimetry were lower than 5% and differences lower than 4% were noted when the absorbed dose responses were compared with ionization chamber, film and TLDs. PMID:23762345

  2. Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host Disease of the Intestine by Expansion of Regulatory T Cells.

    Science.gov (United States)

    Hashimoto, Akari; Sato, Tsutomu; Iyama, Satoshi; Yoshida, Masahiro; Ibata, Soushi; Tatekoshi, Ayumi; Kamihara, Yusuke; Horiguchi, Hiroto; Murase, Kazuyuki; Kawano, Yutaka; Takada, Kohichi; Miyanishi, Koji; Kobune, Masayoshi; Ichimiya, Shingo; Kato, Junji

    2016-01-01

    Narrowband ultraviolet B (NB-UVB) has been widely used in dermatological phototherapy. As for the application of NB-UVB phototherapy to graft-versus-host disease (GVHD), we previously reported that it was highly efficacious for cutaneous lesions of acute GVHD (aGVHD) and that expansion of regulatory T (Treg) cells induced by NB-UVB might be one of the mechanisms. In order to examine whether NB-UVB irradiation through expansion of Treg cells is effective for the treatment of not only cutaneous aGVHD but also aGVHD of inner organs such as the intestine or liver, we conducted experiments in which a murine lethal aGVHD model, characterized by severe involvement of the intestine, was irradiated with NB-UVB. We found that NB-UVB irradiation improved the clinical score and survival rate. The pathological score of aGVHD was improved in all affected organs: intestine, liver, and skin. In the serum of mice irradiated with NB-UVB, the levels of Treg cells-associated cytokines such as transforming growth factor beta (TGFβ) and interleukin-10 (IL-10) were elevated. The numbers of infiltrating Treg cells in inflamed tissue of the intestine and those in spleen were increased in mice treated with NB-UVB. This is the first report demonstrating that NB-UVB phototherapy has the ability to ameliorate intestinal aGVHD through the expansion of Treg cells.

  3. Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant

    Science.gov (United States)

    2016-08-18

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Hodgkin Lymphoma; Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; Waldenstrom Macroglobulinemia

  4. Endoscopic evaluation and histological findings in graft-versus-host disease Evaluación endoscópica y hallazgos histológicos en la enfermedad de injerto contra huésped

    OpenAIRE

    Antonio Velasco-Guardado; Lucía López-Corral; Alberto Álvarez-Delgado; Teresa Flores-Corral; Fernando Geijo-Martínez; Dolores Caballero-Barrigón; Antonio Rodríguez-Pérez

    2012-01-01

    Background: the gastrointestinal (GI) tract is the major target site of the graft-versus-host disease (GVHD). Diagnosis is based on endoscopic and histological findings. Material and methods: we performed a retrospective study from January 1st, 1990 to December 31st, 2008 on 338 upper gastrointestinal endoscopies (gastroscopies) performed to 197 patients that underwent an allogeneic transplant with clinical suspicion of GI-GVHD. Results: endoscopic findings to the diagnosis of GVHD have a sen...

  5. A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    J Luis Espinoza

    Full Text Available Interleukin IL-17 is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. The single nucleotide polymorphism (SNP, rs2275913, in the promoter region of the IL-17 gene is associated with susceptibility to ulcerative colitis. When we examined the impact of rs2275913 in a cohort consisting of 438 pairs of patients and their unrelated donors transplanted through the Japan Marrow Donor Program, the donor IL-17 197A allele was found to be associated with a higher risk of acute graft-versus-host disease (GVHD; hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00 to 2.13; P = 0.05. Next, we investigated the functional relevance of the rs2275913 SNP. In vitro stimulated T cells from healthy individuals possessing the 197A allele produced significantly more IL-17 than those without the 197A allele. In a gene reporter assay, the 197A allele construct induced higher luciferase activity than the 197G allele, and the difference was higher in the presence of T cell receptor activation and was abrogated by cyclosporine treatment. Moreover, the 197A allele displayed a higher affinity for the nuclear factor activated T cells (NFAT, a critical transcription factor involved in IL-17 regulation. These findings substantiate the functional relevance of the rs2275913 polymorphism and indicate that the higher IL-17 secretion by individuals with the 197A allele likely accounts for their increased risk for acute GVHD and certain autoimmune diseases.

  6. T Cells in Predicting Acute Graft-Versus-Host Disease in Patients Undergoing Donor Stem Cell Transplant

    Science.gov (United States)

    2016-06-22

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  7. Lithium Carbonate in Treating Patients With Acute Intestinal Graft-Versus-Host-Disease After Donor Stem Cell Transplant

    Science.gov (United States)

    2011-01-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; De Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Gastrointestinal Complications; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Previously Treated Childhood Rhabdomyosarcoma; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent

  8. Sequential expression of adhesion and costimulatory molecules in graft-versus-host disease target organs after murine bone marrow transplantation across minor histocompatibility antigen barriers.

    Science.gov (United States)

    Eyrich, Matthias; Burger, Gudrun; Marquardt, Katja; Budach, Wilfried; Schilbach, Karin; Niethammer, Dietrich; Schlegel, Paul G

    2005-05-01

    Graft-versus-host disease (GVHD) is a potentially fatal complication after allogeneic bone marrow transplantation. However, few data exist thus far on the molecular signals governing leukocyte trafficking during the disease. We therefore investigated the sequential pattern of distinct adhesion, costimulatory, and apoptosis-related molecules in GVHD organs (ileum, colon, skin, and liver) after transplantation across minor histocompatibility barriers (B10.D2 --> BALB/c, both H-2d). To distinguish changes induced by the conditioning regimen from effects achieved by allogeneic cell transfer, syngeneic transplant recipients (BALB/c --> BALB/c) and irradiated nontransplanted mice were added as controls. Irradiation upregulated the expression of vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-l, and B7-2 in ileum, as well as VCAM-1 and B7-2 in colon, on day 3 in all animals. Whereas in syngeneic mice these effects were reversed from day 9 on, allogeneic recipients showed further upregulation of VCAM-1, ICAM-1, B7-1, and B7-2 in these organs on day 22, when GVHD became clinically evident. Infiltration of CD4+ and CD8+ donor T cells was noted on day 9 in skin and liver and on day 22 in ileum and colon. Surprisingly, the expression of several other adhesion molecules, such as ICAM-2, platelet-endothelial cell adhesion molecule 1, E-selectin, and mucosal addressin cell adhesion molecule 1, did not change. Proapoptotic and antiapoptotic markers were balanced in GVHD organs with the exception of spleen, in which a preferential expression of the proapoptotic Bax could be noted. Our results indicate that irradiation-induced upregulation of VCAM-1, ICAM-1, and B7-2 provides early costimulatory signals to incoming donor T cells in the intestine, followed by a cascade of proinflammatory signals in other organs once the alloresponse is established.

  9. Impact of Cyclosporine Levels on the Development of Acute Graft versus Host Disease after Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Irene García Cadenas

    2014-01-01

    Full Text Available We analyze the impact of cyclosporine (CsA levels in the development of acute graft-versus-host disease (aGVHD after reduced intensity conditioning allogeneic hematopoietic transplantation (allo-RIC. We retrospectively evaluated 156 consecutive patients who underwent HLA-identical sibling allo-RIC at our institution. CsA median blood levels in the 1st, 2nd, 3rd and 4th weeks after allo-RIC were 134 (range: 10–444, 219 (54–656, 253 (53–910 and 224 (30–699 ng/mL; 60%, 16%, 11% and 17% of the patients had median CsA blood levels below 150 ng/mL during these weeks. 53 patients developed grade 2–4 aGVHD for a cumulative incidence of 45% (95% CI 34–50% at a median of 42 days. Low CsA levels on the 3rd week and sex-mismatch were associated with the development of GVHD. Risk factors for 1-year NRM and OS were advanced disease status (HR: 2.2, P=0.02 and development of grade 2–4 aGVHD (HR: 2.5, P<0.01, while there was a trend for higher NRM in patients with a low median CsA concentration on the 3rd week (P=0.06. These results emphasize the relevance of sustaining adequate levels of blood CsA by close monitoring and dose adjustments, particularly when engraftment becomes evident. CsA adequate management will impact on long-term outcomes in the allo-RIC setting.

  10. Hemorrhagic cystitis following hematopoietic stem cell transplantation: incidence, risk factors and association with CMV reactivation and graft-versus-host disease

    Institute of Scientific and Technical Information of China (English)

    XU Lan-ping; ZHANG Yao-chen; LU Dao-pei; ZHANG Hong-yu; HUANG Xiao-jun; LIU Kai-yan; LIU Dai-hong; HAN Wei; CHEN Huan; CHEN Yu-hong; GAO Zhi-yong

    2007-01-01

    Background The definite pathogenesis of hemorrhagic cystitis (HC) after allogenic hematopoietic stem cell transplantation (allo-HSCT) has not been well elucidated. The role of cytomegalovirus (CMV) reactivation and graft-versus-host disease (GVHD) in the development of HC remains obscure. This study determined the incidence and risk factors for HC after allo-HSCT and analyzed its association with CMV reactivation and GVHD. Methods We retrospectively studied 250 patients at high risk for CMV disease who underwent allo-HSCT all based on busulfan/cyclophosphamide (BU/CY) myloablative regimens. The incidence, etiology, risk factors and clinical management of HC were investigated.Results HC developed within 180 days of transplant in 72 patients, with an overall incidence of 28.8% and an incidence of 12.6% in patients with HLA-matched related donors (MRD), 34.38% in those with HLA-matched unrelated donors (MUD), 49.45% in those with mismatched related donors (MMRD). CMV-viremia significantly increased the incidence of later onset HC (LOHC); however, only 9 out of 15 patients with CMV viruria actually developed LOHC. Multiple regression analysis identified grade Ⅱ-Ⅳ acute GVHD (RR=2.75; 95% CI 1.63-4.66; P<0.01) and grafts from MUD or MMRD (RR=2.60; 95% CI 1.52-5.20; P<0.01) as independent risk factors for HC. Event sequence analysis indicated a majority of HC episodes began around GVHD initiation.Conclusions CMV-viremia is a high risk factor for LOHC. Our data also showed a correlation between acute GVHD and HC, which suggested that alloimmunity may be involved in the pathogenesis of HC.

  11. Advances in medical decision support systems for diagnosis of acute graft-versus-host disease: molecular and computational intelligence joint approaches

    Institute of Scientific and Technical Information of China (English)

    Maurizio FIASCH(E); Maria CUZZOLA; Giuseppe IRRERA; Pasquale IACOPINO; Francesco Carlo MORABITO

    2011-01-01

    Acute graft-versus-host disease (aGVHD) is a serious systemic complication of allogeneic hematopoietic stem cell transplantation (HSCT) causing considerable morbidity and mortality.Acute GVHD occurs when alloreactive donor-derived T cells recognize host-recipient antigens as foreign.These trigger a complex multiphase process that ultimately results in apoptotic injury in target organs.The early events leading to GVHD seem to occur very soon,presumably within hours from the graft infusion.Therefore,when the first signs of aGVHD clinically manifest,the disease has been ongoing for several days at the cellular level,and the inflammatory cytokine cascade is fully activated.So,it comes as no surprise that progress in treatment based on clinical diagnosis of aGVHD has been limited in the past 30 years.It is likely that a pre-emptive strategy using systemic high-dose corticosteroids as early as possible could improve the outcome of aGVHD.Due to the deleterious effects of such treatment particularly in terms of infection risk posed by systemic steroid administration in a population that is already immune-suppressed,it is critical to identify biomarker signatures for approaching this very complex task.Some research groups have begun addressing this issue through molecular and proteomic analyses,combining these approaches with computational intelligence techniques,with the specific aim of facilitating the identification of diagnostic biomarkers in aGVHD.In this review,we focus on the aGVHD scenario and on the more recent state-of-the-art.We also attempt to give an overview of the classical and novel techniques proposed as medical decision support system for the diagnosis of GVHD.

  12. Dynamic regulation of effector IFN-γ-producing and IL-17-producing T cell subsets in the development of acute graft-versus-host disease.

    Science.gov (United States)

    Zhao, Kai; Ruan, Suhong; Yin, Lingling; Zhao, Dongmei; Chen, Chong; Pan, Bin; Zeng, Lingyu; Li, Zhenyu; Xu, Kailin

    2016-02-01

    Graft-versus-host disease (GVHD) as the predominant complication of allogeneic hematopoietic stem cell transplantation remains to be fully understood. It is known that the cytokines produced by allogeneic reactive effector CD4+ and CD8+ T cells are involved in GVHD. However, the regulation and coordination of IFN-γ-producing and IL-17-producing effector T cells remain unclear. The present study aimed to investigate the dynamic changes of alloantigen-specific effector CD4+ T and CD8+ T cell subsets by flow cytometry, which produce inflammatory cytokines involved in the multistep GVHD pathogenesis progress. The results demonstrated that IL-17-producing CD8+ T (Tc17) cells and IFN-γ+CD8+ T (Tc1) cells were detected in the early stage of GVHD. The differentiation of CD4+ T cells into Th1 cell (IFN-γ+CD4+ T) and Th17 (IL-17+CD4+ T) cells was later than that of the Tc1 and Tc17 cells. The effector CD4+ T and CD8+ T cell subsets either became exhausted or became memory cells, exhibiting a CD62L-CD44+ phenotype following marked expansion during GVHD. Furthermore, T cell-associated type I (IL-2 and IFN-γ) and type II (IL-4 and IL-10) classical cytokines exhibited coordinated dynamic regulation. It was concluded that the differentiation of cytokine-producing Tc1 and Tc17 cells may be the key step in the initiation of GVHD, whereas CD4+ effector Th1 and Th17 cells are considered to be pathophysiological factors leading to the continuous aggravation of GVHD. PMID:26647759

  13. Radiation-induced mouse chimeras: a cellular analysis of the major lymphoid compartments, factors affecting lethal graft versus host disease and host-tumor interactions

    International Nuclear Information System (INIS)

    The major lymphoid compartments of allogeneic bone marrow chimeras were evaluated for the extent of cell chimerism and distribution of Thy 1 and la bearing cells. These chimeras contained lymphoid cell primarily of donor origin. The bone marrow compartment was a mixture of host and donor origin cells. The distribution of Thy 1 and la bearing cells was similar as in normal mice. The effect of adult thymectomy alone or followed by whole-body irradiation and bone marrow reconstitution on the distribution of the Thy 1 positive cells was also investigated. Thymectomy with or without WBI and bone marrow reconstitution significantly lowered the number of Thy 1 bearing cells in the blood and spleen. The number of la bearing cells did not appear to be affected by thymectomy. The role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation induced fully allogeneic mouse chimeras was studied. Mice reconstituted with allogeneic bone marrow from bled donors had a statistically lower incidence of GVHD than those reconstituted with bone marrow from unbled donors. Addition of mature peripheral lymphocytes from blood to the reconstituting bone marrow cells from bled donors reduplicated the high incidence of lethal GVHD. It was demonstrated that the bone marrow of mice not exsanguinated prior to harvesting of bone marrow contained significant numbers of peripheral contaminating cells in the harvested bone marrow. The role of suppressor cell elimination in resisting tumor growth was investigated using radiation induced mouse chimeras. Local effects of irradiation alone at the site of tumor inoculation could account for this lack of growth

  14. Endothelial microparticles carrying hedgehog-interacting protein induce continuous endothelial damage in the pathogenesis of acute graft-versus-host disease.

    Science.gov (United States)

    Nie, Di-Min; Wu, Qiu-Ling; Zheng, Peng; Chen, Ping; Zhang, Ran; Li, Bei-Bei; Fang, Jun; Xia, Ling-Hui; Hong, Mei

    2016-05-15

    Accumulating evidence suggests that endothelial microparticles (EMPs), a marker of endothelial damage, are elevated in acute graft-versus-host disease (aGVHD), and that endothelial damage is implicated in the pathogenesis of aGVHD, but the mechanisms remain elusive. In this study, we detected the plasma EMP levels and endothelial damage in patients and mice with aGVHD in vivo and then examined the effects of EMPs derived from injured endothelial cells (ECs) on endothelial damage and the role of hedgehog-interacting protein (HHIP) carried by EMPs in these effects in vitro. Our results showed that EMPs were persistently increased in the early posttransplantation phase in patients and mice with aGVHD. Meanwhile, endothelial damage was continuous in aGVHD mice, but was temporary in non-aGVHD mice after transplantation. In vitro, EMPs induced endothelial damage, including increased EC apoptosis, enhanced reactive oxygen species, decreased nitric oxide production and impaired angiogenic activity. Enhanced expression of HHIP, an antagonist for the Sonic hedgehog (SHH) signaling pathway, was observed in patients and mice with aGVHD and EMPs from injured ECs. The endothelial damage induced by EMPs was reversed when the HHIP incorporated into EMPs was silenced with an HHIP small interfering RNA or inhibited with the SHH pathway agonist, Smoothened agonist. This work supports a feasible vicious cycle in which EMPs generated during endothelial injury, in turn, aggravate endothelial damage by carrying HHIP into target ECs, contributing to the continuously deteriorating endothelial damage in the development of aGVHD. EMPs harboring HHIP would represent a potential therapeutic target for aGVHD. PMID:27009877

  15. Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype.

    Directory of Open Access Journals (Sweden)

    Niwa Ali

    Full Text Available The occurrence of Graft-versus-Host Disease (GvHD is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice" are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null, notably the NOD-scid IL-2Rγ(null (NSG and BALB/c-Rag2(null IL-2Rγ(null (BRG mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+ compartment and higher engraftment levels of CD3(+ T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM phenotype and high levels of cutaneous lymphocyte antigen (CLA expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM-cell driven GvHD.

  16. Wharton’s Jelly-Derived Mesenchymal Stromal Cells as a Promising Cellular Therapeutic Strategy for the Management of Graft-versus-Host Disease

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    Joseph P. McGuirk

    2015-04-01

    Full Text Available Allogeneic hematopoietic cell transplantation (allo-HCT, a treatment option in hematologic malignancies and bone marrow failure syndromes, is frequently complicated by Graft-versus-host disease (GVHD. The primary treatment for GVHD involves immune suppression by glucocorticoids. However, patients are often refractory to the steroid therapy, and this results in a poor prognosis. Therefore alternative therapies are needed to treat GVHD. Here, we review data supporting the clinical investigation of a novel cellular therapy using Wharton’s jelly (WJ-derived mesenchymal stromal cells (MSCs as a potentially safe and effective therapeutic strategy in the management of GVHD. Adult-derived sources of MSCs have demonstrated signals of efficacy in the management of GVHD. However, there are limitations, including: limited proliferation capacity; heterogeneity of cell sources; lengthy expansion time to clinical dose; expansion failure in vitro; and a painful, invasive, isolation procedure for the donor. Therefore, alternative MSC sources for cellular therapy are sought. The reviewed data suggests MSCs derived from WJ may be a safe and effective cellular therapy for GVHD. Laboratories investigated and defined the immune properties of WJ-MSCs for potential use in cellular therapy. These cells represent a more uniform cell population than bone marrow-derived MSCs, displaying robust immunosuppressive properties and lacking significant immunogenicity. They can be collected safely and painlessly from individuals at birth, rapidly expanded and stored cryogenically for later clinical use. Additionally, data we reviewed suggested licensing MSCs (activating MSCs by exposure to cytokines to enhance effectiveness in treating GVHD. Therefore, WJCs should be tested as a second generation, relatively homogeneous allogeneic cell therapy for the treatment of GVHD.

  17. Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion

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    Bakonyi Neto Alexandre

    2003-01-01

    Full Text Available Low cytoreductive regimen of irradiation associated to unmodified bone marrow infusion (UBM does not prevent the occurrence of graft versus host disease (GVHD after transplant. PURPOSE: In this study we evaluated the potential advantages of a long-term immunossupression and T-cell depleted bone marrow infusion (TCDBMI in preventing the occurrence of GVHD after small bowel transplantation (SBTx. METHODS: Heterotopic SBTX was performed with Lewis rats as recipients and DA as donors and distributed into 5 groups according to the irradiation, duration of immunossupression and the use of UBM or TCDBMI: G1 (n=6, without irradiation and G2 (n=9, G3 (n=4, G4 (n=5 and G5 (n=6 was given 250 rd of irradiation. Groups 1,2,4 and G3 and 5 were infused with 100 x 10(6 UBM and TCDBM respectively. Animals in G1, 2, 3 were immunossupressed with 1mg/ FK506/Kg/IM for 5 days and G4 and G5 for 15 days. Anti CD3 monoclonal antibodies and immunomagnetic beads were used for T-cell depletion.Animals were examined for rejection, GVHD, chimerism characterization and ileal and skin biopsies. RESULTS: Minimal to mild rejection was observed in all groups; however, GVHD were present only in irradiated groups. Long-term immunossupression changed the severity of GVHD in G4 and G5. Rejection was the cause of death in G1 while GVHD in G2, 3, 4 and 5, not avoided by the use of TCDBMI. Total chimerism and T-cell chimerism was statistically higher in irradiated groups when compared to G1. CONCLUSION: Extended immunossupression associated to low dose of irradiation decrease the severity of GVHD, not avoided by the use of TCDBMI.

  18. Attenuation of graft-versus-host-disease in NOD scid IL-2Rγ(-/-) (NSG) mice by ex vivo modulation of human CD4(+) T cells.

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    Hilger, Nadja; Glaser, Jakob; Müller, Claudia; Halbich, Christoph; Müller, Anne; Schwertassek, Ulla; Lehmann, Jörg; Ruschpler, Peter; Lange, Franziska; Boldt, Andreas; Stahl, Lilly; Sack, Ulrich; Oelkrug, Christopher; Emmrich, Frank; Fricke, Stephan

    2016-09-01

    NOD.Cg-Prkdc(scid) IL-2rg(tm1Wjl) /SzJ (NSG) mice are a valuable tool for studying Graft-versus-Host-Disease (GvHD) induced by human immune cells. We used a model of acute GvHD by transfer of human peripheral blood mononuclear cells (PBMCs) into NSG mice. The severity of GvHD was reflected by weight loss and was associated with engraftment of human cells and the expansion of leukocytes, particularly granulocytes and monocytes. Pre-treatment of PBMCs with the anti-human CD4 antibody MAX.16H5 IgG1 or IgG4 attenuated GvHD. The transplantation of 2 × 10(7) PBMCs without anti-human CD4 pre-treatment induced a severe GvHD (0% survival). In animals receiving 2 × 10(7) PBMCs pre-incubated with MAX.16H5 IgG1 or IgG4, GvHD development was reduced and survival was increased. Immune reconstitution was measured by flow cytometry and confirmed for human leukocytes (CD45), CD3(+) /CD8(+) cytotoxic T cells and CD3(+) /CD4(+) T helper cells. Human B cells (CD19) and monocytes (CD14) could not be detected. Histopathological analysis (TUNEL assay) of the gut of recipient animals showed significantly less apoptotic crypt cells in animals receiving a MAX.16H5 IgG1 pre-incubated graft. These findings indicate that pre-incubation of an allogeneic graft with an anti-human CD4 antibody may decrease the frequency and severity of GvHD after hematopoietic stem cell transplantation (HSCT) and the need of conventional immunosuppressive drugs. Moreover, this approach most probably provides a safer HSCT that must be confirmed in appropriate clinical trials in the future. © 2016 International Society for Advancement of Cytometry. PMID:27560708

  19. Association of HLA-G Low Expressor Genotype with Severe Acute Graft-Versus-Host Disease after Sibling Bone Marrow Transplantation

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    Boukouaci, Wahid; Busson, Marc; Fortier, Catherine; Amokrane, Kahina; de Latour, Régis Peffault; Robin, Marie; Krishnamoorthy, Rajagopal; Toubert, Antoine; Charron, Dominique; Socié, Gérard; Tamouza, Ryad

    2011-01-01

    Background: Human leukocyte antigen-G (HLA-G) molecules play a prominent role in immune tolerance. Structurally similar to their classical HLA homologs, they are distinct by having high rate of polymorphism in the non-coding regions including a functionally relevant 14-base pair (bp) insertion/deletion (Ins/Del) allele in the 3′ untranslated region (3′UTR), rarely examined in a hematopoietic stem cell transplantation (HSCT) setting. Here, we analyzed the potential impact of HLA-G Ins/Del dimorphism on the incidence of acute graft-versus-host disease (aGvHD), transplant-related mortality (TRM), overall survival (OS), and incidence of relapse after HSCT using bone marrow (BM) as stem cell source from HLA-matched donors. Methods: One hundred fifty-seven sibling pairs, who had undergone HSCT, were studied for the distribution of the HLA-G 14 bp Ins/Del polymorphism using a polymerase chain reaction (PCR)-based technique. Potential genetic association with the incidence of aGvHD, TRM, and OS was analyzed by monovariate and multivariate analyses. Results: Monovariate analysis showed that the homozygous state for the 14-bp Ins allele is a risk factor for severe aGvHD (grade III and IV; P = 0.008), confirmed subsequently by multivariate analysis [hazard ratio (HR) = 3.5; 95% confidence interval (95%CI) = 1.3–9.5; P = 0.012]. We did not find any association between HLA-G polymorphism and the other studied complications. Conclusion: Our data suggest that the HLA-G low expressor 14 bp Ins allele constitutes a risk factor for the incidence of severe aGvHD in patients who received BM as stem cell source. PMID:22566863

  20. B7-H3 expression in donor T cells and host cells negatively regulates acute graft-versus-host disease lethality.

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    Veenstra, Rachelle G; Flynn, Ryan; Kreymborg, Katharina; McDonald-Hyman, Cameron; Saha, Asim; Taylor, Patricia A; Osborn, Mark J; Panoskaltsis-Mortari, Angela; Schmitt-Graeff, Annette; Lieberknect, Elisabeth; Murphy, William J; Serody, Jonathan S; Munn, David H; Freeman, Gordon J; Allison, James P; Mak, Tak W; van den Brink, Marcel; Zeiser, Robert; Blazar, Bruce R

    2015-05-21

    Members of the B7 family have been shown to be important for regulating immune responses by providing either positive or negative costimulatory signals. The function of B7-H3 has been controversial. We show that B7-H3 is upregulated in graft-versus-host disease (GVHD) target organs, including the colon, liver, and lung. Infusion of allogeneic donor T cells into B7-H3(-/-) vs wild-type (WT) recipients resulted in increased GVHD lethality associated with increased T-cell proliferation, colonic inflammatory cytokines, and destruction of epithelial barriers. Allogeneic B7-H3(-/-) vs WT donor T cells also had increased T-cell proliferation and GVHD lethality associated with increased proliferation and cytokine secretion in the spleen, intraepithelial lymphocyte inflammatory cytokines, and intestinal permeability. Both resting and activated regulatory T cells (Tregs) lack B7-H3 messenger RNA. Consistent with these data, GVHD was augmented in recipients of B7-H3(-/-) Treg-depleted grafts. In two delayed lymphocyte infusion (DLI) models, T cells lacking B7-H3 are capable of providing graft-versus-leukemia (GVL) effects. We conclude that B7-H3 is responsible for providing a negative costimulatory signal. Our studies provide support for developing and testing new therapies directed toward the B7-H3 pathway, including approaches to augment host B7-H3 early after bone marrow transplantation to prevent GVHD and to develop potent antagonistic antibodies later after transplant to facilitate DLI-mediated GVL without GVHD complications. PMID:25814530

  1. Papel das citocinas na imunopatogênese da doença do enxerto contra o hospedeiro Role of cytokines in the immunopathogenesis of Graft-versus-Host Disease

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    Silvana L. Vizoni

    2008-04-01

    Full Text Available O transplante de células progenitoras hematopoéticas é o tratamento de escolha para muitas doenças hematológicas e imunodeficiências primárias. A doença do enxerto contra o hospedeiro (DECH é ainda uma grave complicação após o transplante alogênico e a principal causa de mortalidade e morbidade. O estudo da patogênese da DECH auxilia no desenvolvimento de medidas preventivas da doença, assim como na escolha de terapias imunossupressoras adequadas de tratamento. Este estudo discute os principais componentes imunológicos envolvidos na patogênese da DECH aguda e crônica, com ênfase à participação das citocinas e seu controle.Stem cell transplantation is the first line treatment of many hematological diseases and primary immunodeficiencies. Graft-versus-host disease (GVHD is still a severe complication after allogeneic transplantation and the main cause of mortality and morbidity. The study of the pathogenesis of GVHD may help to develop ways to prevent the disease, as well as to choose adequate immunosuppressant therapies. This study discusses the main immunological components involved in the pathogenesis of acute and chronic GVHD, with emphasis on the participation of cytokines and their control.

  2. Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

    International Nuclear Information System (INIS)

    Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT

  3. Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

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    Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Yu, Xue-Zhong [Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425 (United States); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2014-04-18

    Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.

  4. CD103 deficiency prevents graft-versus-host disease but spares graft-versus-tumor effects mediated by alloreactive CD8 T cells.

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    Kechang Liu

    Full Text Available BACKGROUND: Graft-versus-host disease (GVHD remains the main barrier to broader application of allogeneic hematopoietic stem cell transplantation (alloSCT as a curative therapy for host malignancy. GVHD is mediated by allogeneic T cells directed against histocompatibility antigens expressed by host tissues. Based on previous studies, we postulated that the integrin CD103 is required for CD8-mediated GVHD, but not for graft-versus-tumor effects (GVT. METHODOLOGY/PRINCIPAL FINDINGS: We herein provide evidence in support of this hypothesis. To circumvent the potentially confounding influence of donor CD4 T cells, we developed an alloSCT model in which GVHD mortality is mediated by purified CD8 T cells. In this model, host-reactive CD8 T cells receive CD4 T cell help at the time of initial activation but not in the effector phase in which mature CD8 T effectors migrate into host tissues. We show that donor CD8 T cells from wild-type BALB/c mice primed to host alloantigens induce GVHD pathology and eliminate tumors of host origin in the absence of host CD4 T cells. Importantly, CD103 deficiency dramatically attenuated GVHD mortality, but had no detectable impact on the capacity to eliminate a tumor line of host origin. We provide evidence that CD103 is required for accumulation of donor CD8 T cells in the host intestinal epithelium but not in the tumor or host lymphoid compartments. Consistent with these data, CD103 was preferentially expressed by CD8 T cells infiltrating the host intestinal epithelium but not by those infiltrating the tumor, lamina propria, or lymphoid compartments. We further demonstrate that CD103 expression is not required for classic CD8 effector activities including cytokine production and cytotoxicity. CONCLUSIONS/SIGNIFICANCE: These data indicate that CD103 deficiency inhibits GVHD pathology while sparing anti-tumor effects mediated by CD8 T cells, identifying CD103 blockade as an improved strategy for GVHD prophylaxis.

  5. Effects of bone marrow mesenchymal stem cells on hematopoietic recovery and acute graft-versus-host disease in murine allogeneic umbilical cord blood transplantation model.

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    Li, Zhen Yu; Wang, Chun Qing; Lu, Guang; Pan, Xiu Ying; Xu, Kai Lin

    2014-09-01

    To investigate the effect of bone marrow mesenchymal stem cells (MSC) on hematopoietic recovery and acute graft-versus-host disease (GVHD) in a murine allogeneic umbilical cord blood transplantation (allo-UCBT) model. MSCs were obtained from C57/BL mouse bone marrow. The MSC phenotypes were identified by flow cytometry (FCM), and their ability to differentiate into osteoblasts and adipocytes was tested. Once murine allo-UCBT and aGVHD models were established, mice were divided into five groups: (1) total body irradiation (TBI) group, each mouse receiving 0.3 ml sterile saline infusion after TBI and used as control; (2) UCB group, receiving 2 × 10(6) umbilical cord blood mononuclear cells (UCB-MNC) after TBI; (3) UCB+MSC group, receiving 2 × 10(6) UCB-MNC and 2 × 10(7) MSC after TBI; (4) UCB+SC group, receiving 2 × 10(6) UCB-MNC and 2 × 10(6) spleen cells after TBI; and (5) UCB+SC+MSC group, receiving 2 × 10(6) UCB-MNC, 2 × 10(7) MSC and 2 × 10(6) spleen cells after TBI. To evaluate the engraftment of HSC, the white blood cells, red blood cells, and platelets counts were tested at different time points after transplantation, and the ratio of chimerism was identified by FCM. The acute GVHD clinical scores, recipient mice survival, and the histopathological analyses were used to evaluate the effect of MSC on acute GVHD. MSCs were successfully obtained in vitro and FCM analysis showed that these cells are highly positive for CD90.2, CD44, and negative for CD34, CD45, and they are capable to differentiate into osteoblasts and adipocytes after being induced. Compared to UCB group, the UCB+MSC mice had shorter duration of myelosuppression and higher percentage of donor-derived cells which was up to 22.87 ± 4.3 % and the white blood cell (WBC), red blood cell (RBC), and platelet counts started to increase by day 6 after transplantation. Moreover, the average survival time for UCB+MSC mice was 25.0 ± 10.55 days, while for the UCB group it was 15.5 ± 12.50 days

  6. Recurrent corneal perforation due to chronic graft versus host disease; a clinicopathologic report

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    Mehrdad Mohammadpour

    2016-01-01

    Conclusion: Patients with GVHD are at risk of severe dry eye and subsequent corneal vascularization. Recurrent and recalcitrant corneal perforation resistant to cyanoacrylate glue and multilayer AMT may occur. Proper systemic and ocular management alongside close collaboration with the hematologist is strongly recommended to control the condition.

  7. Role of acute graft-versus-host disease in the risk of bacteremia and invasive fungal disease after allogeneic hemopoietic stem cell transplantation in children. Results from a single-center observational study.

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    Castagnola, Elio; Bagnasco, Francesca; Bandettini, Roberto; Caviglia, Ilaria; Morreale, Giuseppe; Lanino, Edoardo; Giardino, Stefano; Moroni, Cristina; Haupt, Riccardo; Faraci, Maura

    2014-07-01

    Data on epidemiology of severe infectious complications, ie, bacteremia or invasive fungal disease (IFD), in children with acute graft-versus-host disease (aGVHD) after allogeneic hemopoietic stem cell transplantation (HSCT) are scarce. In a retrospective, single-center study, we analyzed the risk (hazard ratio [HR]) and the rate (episodes/1000 patients days at risk) of bacteremias and IFD in children receiving allogeneic HSCT, according to the type of donor (matched related [MRD] or alternative [AD]) and presence and grade of aGVHD. From 2000 to 2009, 198 children receiving 217 allogeneic HSCT developed 134 severe infectious episodes (103 bacteremias and 31 IFD). The type of donor (AD versus MRD) was the most important risk factor for the severe infections (P = .0052). In separate multivariable analysis for bacteremia and IFD, children receiving an AD HSCT had increased HR and rate of bacteremia compared with those receiving a MRD transplantation (P = .0171 and P = .0001, respectively), whereas the HR and the rate of IFD were significantly influenced by the grade of aGVHD (P = .0002 and P design management strategies of infections in pediatric allogeneic HSCT.

  8. Methotrexate Reduces the Incidence of Severe Acute Graft-versus-Host Disease without Increasing the Risk of Relapse after Reduced-Intensity Allogeneic Stem Cell Transplantation from Unrelated Donors.

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    Vigouroux, Stéphane; Tabrizi, Reza; Melot, Cyril; Coiffard, Joelle; Lafarge, Xavier; Marit, Gérald; Bouabdallah, Krimo; Pigneux, Arnaud; Leguay, Thibaut; Dilhuydy, Marie-Sarah; Schmitt, Anna; Boiron, Jean-Michel; Milpied, Noël

    2011-01-01

    Optimized prophylaxis against graft-versus-host disease (GVHD) after unrelated reduced-intensity allogeneic transplantation when preceded by a conditioning regimen utilizing antithymocyte globulin (ATG) is poorly defined. To investigate the effects of methotrexate (MTX) in this treatment setting, we conducted a retrospective analysis. Sixty-three patients were selected based on the administration of a total dose of 5 mg/kg of ATG in the conditioning regimen and then separated into either group M+ (n = 39), which received MTX or group M- (n = 24), which did not. All patients received cyclosporine. In the M- and M+ groups, cumulative incidences (CI) of grade III-IV acute GVHD (aGVHD) were 43% and 10%, respectively (P = .002). Multivariate analysis indicated that grade III-IV aGVHD was favored by both the absence of MTX and the provision of a female donor for a male recipient. At 2 years, the M+ and M- groups exhibited, respectively: overall survival of 69% and 40% (P = .06), disease-free survival of 57% and 43% (P = .2), nonrelapse mortality of 20% and 44% (P = .1), and incidence of relapse of 27% and 35% (P = .6). These data suggest that MTX reduces the incidence of severe aGVHD without increasing the risk of relapse but with an accompanying trend toward improved survival after unrelated reduced-intensity transplantation with ATG in the conditioning regimen.

  9. Freeze and Thaw of CD4+CD25+Foxp3+ Regulatory T Cells Results in Loss of CD62L Expression and a Reduced Capacity to Protect against Graft-versus-Host Disease.

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    Mareike Florek

    Full Text Available The adoptive transfer of CD4+CD25+Foxp3+ regulatory T cells (Tregs in murine models of allogeneic hematopoietic cell transplantation (HCT has been shown to protect recipient mice from lethal acute graft-versus-host disease (GVHD and this approach is being actively investigated in human clinical trials. Here, we examined the effects of cryopreservation on Tregs. We found that freeze and thaw of murine and human Tregs is associated with reduced expression of L-selectin (CD62L, which was previously established to be an important factor that contributes to the in vivo protective effects of Tregs. Frozen and thawed murine Tregs showed a reduced capacity to bind to the CD62L binding partner MADCAM1 in vitro as well as an impaired homing to secondary lymphoid organs in vivo. Upon adoptive transfer frozen and thawed Tregs failed to protect against lethal GVHD compared with fresh Tregs in a murine model of allogeneic HCT across major histocompatibility barriers. In summary, the direct administration of adoptively transferred frozen and thawed Tregs adversely affects their immunosuppressive potential which is an important factor to consider in the clinical implementation of Treg immunotherapies.

  10. IL-22 promoted CD3+ T cell infiltration by IL-22R induced STAT3 phosphorylation in murine acute graft versus host disease target organs after allogeneic bone marrow transplantation.

    Science.gov (United States)

    Zhao, Kai; Ruan, Suhong; Tian, Yu; Zhao, Dongmei; Chen, Chong; Pan, Bin; Yan, Zhiling; Yin, Lingling; Zhu, Shengyun; Xu, Kailin

    2016-10-01

    Graft versus host disease (GVHD) is a life threatening complication of bone marrow stem cell transplantation, in which considerable numbers of proinflammatory cytokines secreted by allo-reactive donor T cells are involved. We and other previous studies have found that interleukin-22 (IL-22) was able to aggravate the target organs damage of GVHD. However, the mechanism and the signal pathway of IL-22 in murine acute GVHD was not clear. Here, we observed that compared with GVHD group, more serious pathological damage and more CD3(+) T cells infiltrated in GVHD target organs were detected in the mice injected with IL-22. Meanwhile, transcription factor T-bet, RORγt and AhR respectively associated with Th1, Th17 and Th22 cells changed in varying degrees in different GVHD target organs. Furthermore, the increased expression of IL-22R and its downstream protein P-STAT3 were detected in GVHD mice with IL-22 treated. These results suggested that the pathological role of IL-22 in GVHD target organs contribute to exogenous injected IL-22 as well as secreted IL-22 from the infiltrated allo-reactive effector T cells. In addition, the IL-22R-STAT3 pathway may play important role in GVHD tissue injury and target this way may yield new approaches for reduction of GVHD. PMID:27551984

  11. Sirolimus, Cyclosporine, and Mycophenolate Mofetil in Preventing Graft-versus-Host Disease in Treating Patients With Hematologic Malignancies Undergoing Donor Peripheral Blood Stem Cell Transplant

    Science.gov (United States)

    2016-09-06

    Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloid Leukemia; Adult Diffuse Large B-Cell Lymphoma; Adult Myelodysplastic Syndrome; Adult Non-Hodgkin Lymphoma; Aggressive Non-Hodgkin Lymphoma; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia; Childhood Diffuse Large B -Cell Lymphoma; Childhood Myelodysplastic Syndrome; Childhood Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Chronic Lymphocytic Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphoid Cell Neoplasm; Mantle Cell Lymphoma; Plasma Cell Myeloma; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  12. Benzimidazoisoquinolines: a new class of rapidly metabolized aryl hydrocarbon receptor (AhR ligands that induce AhR-dependent Tregs and prevent murine graft-versus-host disease.

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    Sumit Punj

    Full Text Available The aryl hydrocarbon receptor (AhR is a ligand-activated transcription factor that plays multiple roles in regulation of immune and inflammatory responses. The ability of certain AhR ligands to induce regulatory T cells (Tregs has generated interest in developing AhR ligands for therapeutic treatment of immune-mediated diseases. To this end, we designed a screen for novel Treg-inducing compounds based on our understanding of the mechanisms of Treg induction by the well-characterized immunosuppressive AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD. We screened a ChemBridge small molecule library and identified 10-chloro-7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (10-Cl-BBQ as a potent AhR ligand that was rapidly metabolized and not cytotoxic to proliferating T cells. Like TCDD,10-Cl-BBQ altered donor CD4(+ T cell differentiation during the early stages of a graft versus host (GVH response resulting in expression of high levels of CD25, CTLA-4 and ICOS, as well as several genes associated with Treg function. The Treg phenotype required AhR expression in the donor CD4(+ T cells. Foxp3 was not expressed in the AhR-induced Tregs implicating AhR as an independent transcription factor for Treg induction. Structure-activity studies showed that unsubstituted BBQ as well as 4, 11-dichloro-BBQ were capable of inducing AhR-Tregs. Other substitutions reduced activation of AhR. Daily treatment with 10-Cl-BBQ during the GVH response prevented development of GVH disease in an AhR-dependent manner with no overt toxicity. Together, our data provide strong support for development of select BBQs that activate the AhR to induce Tregs for treatment of immune-mediated diseases.

  13. Inhibition of calcineurin abrogates while inhibition of mTOR promotes regulatory T cell expansion and graft-versus-host disease protection by IL-2 in allogeneic bone marrow transplantation.

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    Atsushi Satake

    Full Text Available Regulatory T cells (Tregs attenuate excessive immune responses, making their expansion beneficial in immune-mediated diseases including allogeneic bone marrow transplantation (BMT-associated graft-versus-host disease (GVHD. We have recently reported that Treg expansion does not require phospholipase Cγ activation when IL-2 is provided. As such, the combination of IL-2 and a calcineurin inhibitor (Cyclosporine A; CsA expands Tregs while inhibiting Tconv proliferation and protects against a mouse model of multiple sclerosis. However, CsA inhibits Treg proliferation in the presence of a TCR stimulus, suggesting that CsA may negatively impact Treg proliferation when they receive strong allogeneic MHC-mediated TCR signals. In this study, we show that CsA inhibits Treg proliferation and inducible Treg generation in allogeneic but not in syngeneic BMT when IL-2 is provided. In contrast to CsA, the mTOR inhibitor (Rapamycin almost completely suppressed IL-2-mediated Treg proliferation. However, CsA and Rapamycin inhibited Treg proliferation to a similar extent when TCR stimulation was provided. Furthermore, Rapamycin promoted Treg expansion and inducible Treg generation in allogeneic BMT recipients treated with IL-2. Consistent with these observations, CsA abrogated while Rapamycin promoted the protective effect of IL-2 on allogeneic BMT-induced GVHD. These results suggest that while CsA permits IL-2-induced Treg proliferation in the syngeneic setting (absence of strong TCR signals, CsA in combination with IL-2 may be detrimental for Treg proliferation in an allogeneic setting. Thus, in allogeneic settings, an mTOR inhibitor such as Rapamycin is a better choice for adjunct therapy with IL-2 in expansion of Tregs and protection against allogeneic BMT-induced GVHD.

  14. Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

    Science.gov (United States)

    2015-08-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Myeloid Leukemia in Remission; Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell

  15. Metagenomic Analysis of the Stool Microbiome in Patients Receiving Allogeneic Stem Cell Transplantation: Loss of Diversity Is Associated with Use of Systemic Antibiotics and More Pronounced in Gastrointestinal Graft-versus-Host Disease

    Science.gov (United States)

    Holler, Ernst; Butzhammer, Peter; Schmid, Karin; Hundsrucker, Christian; Koestler, Josef; Peter, Katrin; Zhu, Wentao; Sporrer, Daniela; Hehlgans, Thomas; Kreutz, Marina; Holler, Barbara; Wolff, Daniel; Edinger, Matthias; Andreesen, Reinhard; Levine, John E.; Ferrara, James L.; Gessner, Andre; Spang, Rainer; Oefner, Peter J.

    2016-01-01

    Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 µmol/L to 11.8 ± 2.8 µmol/L in all post-transplant samples and to 3.5 ± 3 µmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT. PMID:24492144

  16. Graft monocytic myeloid-derived suppressor cell content predicts the risk of acute graft-versus-host disease after allogeneic transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells.

    Science.gov (United States)

    Vendramin, Antonio; Gimondi, Silvia; Bermema, Anisa; Longoni, Paolo; Rizzitano, Sara; Corradini, Paolo; Carniti, Cristiana

    2014-12-01

    Myeloid-derived suppressor cells (MDSCs) are powerful immunomodulatory cells that in mice play a role in infectious and inflammatory disorders, including acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Their relevance in clinical acute GVHD is poorly known. We analyzed whether granulocyte colony-stimulating factor (G-CSF) administration, used to mobilize hematopoietic stem cells, affected the frequency of MDSCs in the peripheral blood stem cell grafts of 60 unrelated donors. In addition, we evaluated whether the MDSC content in the peripheral blood stem cell grafts affected the occurrence of acute GVHD in patients undergoing unrelated donor allogeneic stem cell transplantation. Systemic treatment with G-CSF induces an expansion of myeloid cells displaying the phenotype of monocytic MDSCs (Lin(low/neg)HLA-DR(-)CD11b(+)CD33(+)CD14(+)) with the ability to suppress alloreactive T cells in vitro, therefore meeting the definition of MDSCs. Monocytic MDSC dose was the only graft parameter to predict acute GVHD. The cumulative incidence of acute GVHD at 180 days after transplantation for recipients receiving monocytic MDSC doses below and above the median was 63% and 22%, respectively (P = .02). The number of monocytic MDSCs infused did not impact the relapse rate or the transplant-related mortality rate (P > .05). Although further prospective studies involving larger sample size are needed to validate the exact monocytic MDSC graft dose that protects from acute GVHD, our results strongly suggest the modulation of G-CSF might be used to affect monocytic MDSCs graft cell doses for prevention of acute GVHD.

  17. Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant

    Science.gov (United States)

    2016-03-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Clear Cell Renal Cell Carcinoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell

  18. Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

    Science.gov (United States)

    2015-10-14

    Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Refractory Chronic Lymphocytic Leukemia; Refractory Plasma Cell Myeloma; Waldenstrom Macroglobulinemia; Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Lymphoma; Childhood Myelodysplastic Syndrome; Stage II Contiguous Adult Burkitt Lymphoma; Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Contiguous Adult Diffuse Mixed Cell Lymphoma; Stage II Contiguous Adult Diffuse Small Cleaved Cell Lymphoma; Stage II Adult Contiguous Immunoblastic Lymphoma; Stage II Contiguous Adult Lymphoblastic Lymphoma; Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Contiguous Mantle Cell Lymphoma; Stage II Non-Contiguous Adult Burkitt Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Mixed Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Small Cleaved Cell Lymphoma; Stage II Adult Non-Contiguous Immunoblastic Lymphoma; Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage

  19. 胃肠型GVHD患者不同营养方案的临床疗效%Clinical effect of different nutrition supporting schemes on gastrointestinal graft-versus-host disease

    Institute of Scientific and Technical Information of China (English)

    李云龙; 张曦; 高蕾; 刘耀; 高力; 张诚; 刘焕凤; 刘学; 陈幸华

    2011-01-01

    Objective To compare the effect of two nutrition supporting schemes for the improvement of the nutrition situation and the therapy of patients with gastrointestinal graft-versus-host disease(GVHD). Methods 35 cases of patients with gastrointes tinal GVHD were randomly divided into total praenteral nutrition(TPN) group and oral diet(OD) group. The nutrition situation and therapeutic effect of the two groups were evaluated before therapy,and on the 14th and 28th day after therapy. Results Nitrogen balance was negative in all subjects on the 14th and 28th day. The remission rate of TPN group was higher than that of OD group(P<0.05). Conclusion The nutritional situation of patients with gastrointestinal GVHD are poor, and might get worse with the extension of the course of disease. The aggravating speed of nutritional situation in patients with gastrointestinal GVHD accepting TPN scheme might be slow,indicating that TPN scheme could be beneficial to patients with gastrointestinal GVHD.%目的 比较不同营养支持方案对胃肠道移植物抗宿主病(GVHD)患者营养状况改善的作用,并对不同营养方案进行评价,观察不同营养方案对胃肠道GVHD辅助治疗的疗效.方法 对35例胃肠道GVHD患者随机分为完全肠外营养组(TPN)和经口饮食组(OD),分别于治疗后的0、14、28 d评价患者的营养状况和GVHD临床疗效.结果 35例胃肠道GVHD患者在治疗后14、28 d均为负氮平衡.患者的GVHD临床症状缓解率显示,TPN组大于OD组,P<0.05.结论 胃肠道GVHD患者属于营养不良状况,并且随着疾病时间的延长,营养不良状况加重,加重的程度TPN组最慢.TPN有助于抗胃肠道GVHD治疗.

  20. Endoscopic evaluation and histological findings in graft-versus-host disease Evaluación endoscópica y hallazgos histológicos en la enfermedad de injerto contra huésped

    Directory of Open Access Journals (Sweden)

    Antonio Velasco-Guardado

    2012-06-01

    Full Text Available Background: the gastrointestinal (GI tract is the major target site of the graft-versus-host disease (GVHD. Diagnosis is based on endoscopic and histological findings. Material and methods: we performed a retrospective study from January 1st, 1990 to December 31st, 2008 on 338 upper gastrointestinal endoscopies (gastroscopies performed to 197 patients that underwent an allogeneic transplant with clinical suspicion of GI-GVHD. Results: endoscopic findings to the diagnosis of GVHD have a sensitivity (S of 34%, specificity levels (SP of 65%, a positive predictive value (PPV of 73% and a negative predictive value (NPV of 48%. The histological study of the endoscopic biopsies has a global sensibility of 85.6% SP = 34.6% PPV = 64.2% and NPV = 63.7%. Histological grade was correlated with the clinical grade of acute GVHD (p = 0.018. Conclusion: upper gastrointestinal endoscopy is useful for the diagnosis of GVHD, as it allows biopsies that can ultimately lead to the diagnosis, but with limited accuracy because the histological findings have low sensitivity and specificity, while the endoscopic findings are generally nonspecific.Introducción: el tracto gastrointestinal es la diana principal de afectación en la enfermedad de injerto contra huésped (EICH. Su diagnóstico se basa en los hallazgos endoscópicos e histológicos. Material y métodos: hemos realizado un estudio retrospectivo, desde el 1 de enero de 1990 hasta el 30 de diciembre de 2008, de 338 endoscopias digestivas altas realizadas a 197 pacientes sometidos a trasplante alogénico de células hematopoyéticas con sospecha de EICH gastrointestinal. Resultados: los hallazgos endoscópicos tienen una sensibilidad (S del 34%, especificidad (E del 65%, valor predictivo positivo (VPP del 73% y valor predictivo negativo (VPN del 48% para el diagnóstico de EICH. El estudio histológico de las biopsias tiene una S del 85,6%, E del 34,6%, VPP del 64,2% y VPN del 63,7%. El grado histológico se

  1. Experimental study of ANNAO tablets on preventing acute graft-versus-host disease in bone marrow transplanted mice%安脑片干预异体移植小鼠aGVHD效应的实验研究

    Institute of Scientific and Technical Information of China (English)

    吴顺杰; 罗藤; 黄海定

    2012-01-01

    In order to observe the effect of ANNAO tablets on acute graft versus host disease, we set up an acute graft-versus-host disease mouse model. Hematopoietic stem cells of male Balb/c mice were transplanted to female C57BL/6 mice, which was irradiated by 60Co X rays with dose 9.0 Gy before transplantation. Then recipient mice were randomly divided into two groups (ANNAO group and blank group), and respectively administrated with ANNAO soup and 0.9% sodium chloride intragastrically. We observed and recorded clinical symptom, survival time and body weight of mice everyday during observation time. At day 15 posttransplantation, three mice died and seven mice survived in ANNAO group, and their mean survival time was 27.3 days, which was much longer than blank group (their mean survival time was 11.9 days). The majority of ANNAO group demonstrated good mental state, good appetite, no weigh loss, normal stool, and burnish hairs after day 12. Their clinical scores of skin, weight, diarrhea, posture and activity were respectively 0.10 ± 032, 020 ± 0.42, 0.12 ± 0.00, and 0.10 ± 0.10, with the whole score of ANNAO group being 0.31 ± 0.14, which was distinctly different as compared with that of blank group (P = 0.000). 30 days later, survived mice were sacrificed and the samples of liver, intestine and skin were taken to observe histological features. We found there some improvements in liver, skin, and intestine tissue of ANNAO group as compared with blank control group. In conclusion, ANNAO tablets can relieve symptoms of acute GVHD mice effectively and prolong their survival time, and improve histopathological manifestations.%目的 观察中药安脑片对异体移植小鼠aGVHD的干预作用.方法 SPF级Balb/c雄性小鼠作为供鼠.以SPF级C57BL/6雌性小鼠为受鼠,建立aGVHD模型,分为安脑片组和空白组,每组10只.观察期间记录小鼠的一般状况及称质量、存活时间,给予临床aGVHD评价,移植后第30天杀鼠取材,制备肝脏、

  2. Allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia:a report of 12 patients

    Institute of Scientific and Technical Information of China (English)

    孙于谦

    2013-01-01

    Objective To retrospectively review the efficacy of allogeneic hematopoietic stem cell transplantation(allo-HSCT)for chronic myelomonocytic leukemia(CMML).Methods The engraftment,graft versus host disease(GVHD)

  3. Multipotent Mesenchymal Stromal Cells for the Prophylaxis of Acute Graft-versus-Host Disease—A Phase II Study

    Directory of Open Access Journals (Sweden)

    Larisa A. Kuzmina

    2012-01-01

    Full Text Available The efficacy and the safety of the administration of multipotent mesenchymal stromal cells (MMSCs for acute graft-versus-host disease (aGVHD prophylaxis following allogeneic hematopoietic cell transplantation (HSCT were studied. This prospective clinical trial was based on the random patient allocation to the following two groups receiving (1 standard GVHD prophylaxis and (2 standard GVHD prophylaxis combined with MMSCs infusion. Bone marrow MMSCs from hematopoietic stem cell donors were cultured and administered to the recipients at doses of 0.9–1.3×106/kg when the blood counts indicated recovery. aGVHD of stage II–IV developed in 38.9% and 5.3% of patients in group 1 and group 2, respectively, (=0.002. There were no differences in the graft rejection rates, chronic GVHD development, or infectious complications. Overall mortality was 16.7% for patients in group 1 and 5.3% for patients in group 2. The efficacy and the safety of MMSC administration for aGVHD prophylaxis were demonstrated in this study.

  4. Tacrolimus and Mycophenolate Mofetil in Preventing Graft-Versus-Host Disease in Patients Who Have Undergone Total-Body Irradiation With or Without Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant for Hematologic Cancer

    Science.gov (United States)

    2016-01-25

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous

  5. 非清髓性造血干细胞移植后并发移植物抗宿主病的相关因素分析%Related factor analysis of graft-versus-host disease post nonmyeloablative stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    李庆山; 毛平; 王顺清; 莫文健; 张玉平; 应逸; 邓婷芬

    2008-01-01

    目的 探讨和分析非清髓性造血干细胞移植(NST)后并发移植物抗宿主病(GVHD)的相关因素.方法 选择34例血液病患者,其中重型再生障碍性贫血(SAA)15例,重型β-地中海贫血(TM)1例,肿瘤性血液病18例;进行无关供者脐带血造血干细胞移植(UCBT)11例,同胞供者骨髓联合外周血干细胞移植7例,外周血造血干细胞移植(PBSCT)16例.移植前采用以抗胸腺细胞球蛋白(ATG)、抗淋巴细胞球蛋白(ALG)或者氟达拉滨强效免疫抑制为基础的非清髓性预处理方案.GVHD的预防采用短程的甲氨蝶呤(MTX)联合环孢素A(CsA).观察非清髓性造血干细胞移植后的临床特点以及急、慢性移植物抗宿主病的发生情况;分析发生慢性移植物抗宿主病(cGVHD)的相关因素.结果 NST的植入率为91.2%.移植后7例肿瘤性血液病患者形成了供、受者造血细胞混合嵌合体(MC),给予供者淋巴细胞输注(DLI)2~9次后,例由MC转变为供者造血细胞完全嵌合体(FDC).随访12(3~96)个月,共发生Ⅰ~Ⅱ度急性移植物抗宿主病(aGVHD)5例,GVHD 15例.经统计学分析,发现年龄大的肿瘤性血液病患者经以ATG为基础的NST后,再给予DLI,其cGVHD的发生率高,且合并感染,对治疗的反应差;而以氟达拉滨为基础的NST患者发生cGVHD后治疗反应较好.移植100 d前后患者分别死亡3例和5例,其中3例死于广泛性cGVHD.结论 患者的年龄大、有合并症、以ATG为基础的预处理方案、肿瘤性血液病是NST后患者并发cGVHD的危险因素.%Objective To explore and analyze the related factors of graft-versus-host disease (GVHD) post nonmyeloablative stem cell transplantation (NST) for haematologic diseases.Methods Thirty-four patients including severe aplastic anemia (SAA) (n=15),halassemia major (TM) (n=1) and malignant haematologie diseases (n=18) underwent unrelated umbilical cord blood transplantation (UCBT) (n=11) and sibling donor bone and peripheral

  6. PCR-STR在肝移植后移植物抗宿主病中的诊断意义%Short tandem repeat loci analysis with polymerase chain reaction in the diagnosis of graft-versus-host disease after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    陈小平; 骆利敏; 罗敏; 肖露露

    2012-01-01

    Objective To assess the value of short tandem repeat (STR) analysis with fluorescence labeling polymerase chain reaction (PCR) in evaluating the status of engraftment and predicting the occurrence of graft-versus-host disease (GVHD) following orthotopic liver transplantation.Methods The method of STR analysis with fluorescence labeling PCR was established.DNA was extracted by monoclonal magnetic beads from the peripheral blood nucleated cells of 23 recipients and labeled with 4 fluorescence dyes before and at 7 days after orthotopic liver transplantation.Results In the 23 patients studied,5 patients showed mixed chimeras after orthotopic liver transplantation.Two of the 5 patients with mixed chimeras developed GVHD and died.The other 18 patients did not show mixed chimeras,and only one of them developed GVHD.The incidence of GVHD was significantly different between the patients with and without mixed chimeras (40% vs 5.6%,P<0.05).Conclusions PCR-STR analysis after orthotopic liver transplantation can be indicative of engraftment and help to predict the occurrence of GVHD following orthotopic liver transplantation.%目的 为了准确地识别肝脏移植物的植入状态,探讨多聚酶链反应-短串联重复序列(PCR-STR)技术在肝移植后移植物抗宿主病中的预测和诊断意义.方法 建立荧光标记PCR-STR等位基因分析技术,采用单克隆磁珠提取DNA,四色荧光标记,于移植前和移植后1周内,采集供、受血液DNA作PCR-STR分析.结果 23例患者中,5例患者供受者HLA完全嵌合表达,其中2例发生移植物抗宿主病(GVHD),均治疗无效死亡,另外3例未发生GVHD,顺利恢复出院,GVHD发生率40%.18例患者术后未发生嵌合表达,其中1例发生GVHD,家属放弃治疗出院,GVHD发生率5.6%,两组有显著差别.结论 基于分子水平的多位点PCR-STR可以提供肝脏移植后供体植入信息,在肝移植后移植物抗宿主病的诊断中具有一定的预测意义.

  7. Experimental study of G-CSF alleviating graft-versus-host disease after mixed bone marrow transplantation in mice%粒细胞集落刺激因子减轻混合骨髓移植后移植物抗宿主病的实验研究

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: How to reduce the incidence and severity of acute graft-versus-host disease (aGVHD) is a crucial step to improve the overall survival of allogeneic bone marrow transplantation (allo-BMT). The low incidence of severe aGVHD observed in allogeneic peripheral blood stem cell transplantation (allo-PBSCT), which may be related to modulating immune function of T lymphocytes by granulocyte colony-stimulating factor (G-CSF) primed donors. The study aimed to explore whether aGVHD could be alleviated by syngeneic bone marrow mixed with G-CSF-mobilized H-2 haploidentical marrow grafting. Methods: Female BALB/c mice and neonatal BALB/c mice were recipients and male (BALB/c × C57BL/6)F1(BCF1)mice were donor mice respectively. Donor mice were injected subcutaneously with G-CSF daily at 0.01 μg/g body weight or saline for 6 days, and splenocytes were harvested on day 6. Spleen index (SI) represented GVHD in neonatal mice after the intraperitoneal injection of mixed spleen cells. Lethally irradiated (60Co, 8.5 Gy) adult mice were transplanted with a mixture of syngeneic plus G-CSF-mobilized (control diluents) H-2 haploidentical marrow cells. Survival time and survival rate of the recipients were observed after mixed marrow transplantation (MBMT). GVHD was assessed by observing signs of weight loss, ruffled fur, diarrhea and histological change of skin, liver and small intestines. Enzyme-linked immunosorbent assay (ELISA) method was used to detect cytokines (IL-2, IL-4 and INF-Y). Fluorescence-activated cell sorting (FACS) analysis was used to detect T cells phenotype. Results: (1) The neonatal mice subject to injection of 2:1 and 1:1 mixed spleen cells and H-2 haploidentical spleen cells all suffered from aGVHD. The severity of aGVHD in recipient mice receiving G-CSF-mobilized splenocytes was dramatically reduced. (2) The aGVHD signs and histological change were observed in most mice of 2:1 and 1:1 MBMT groups. However, the survival time of G-CSF-mobilized MBMT was

  8. Prevention of cyclosporine A combined with Cobalt protoporphyrin against murine graft-versus-host disease after allogeneic hematopoietic stem cell transplantation%环孢素A联合钴原卟啉预防小鼠HSCT后移植物抗宿主病

    Institute of Scientific and Technical Information of China (English)

    王祥民; 潘秀英; 曾令宇; 安立才; 陈伟; 张翠平; 潘彬; 徐开林

    2012-01-01

    Objective To explore prevention of cyclosporine A (CsA) combined with Cobalt protoporphyrin (CoPP) against murine graft versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods C57BL/6 (H-2Kb) mice were used as donors and BALB/c (H-2Kd) mice as recipients,which were randomly divided into 4 groups.The mice in total body irradiation group (TBI group) were lethally irradiated and injected intravenously with PBS; The mice in Allo-HSCT group (BS group) were lethally irradiated and injected intravenously with bone marrow cells and spleen cells; The mice in CsA intervention group (CsA group) were injected with CsA intraperitoneally after allo-HSCT; The mice in CsA combine with CoPP intervention group (combination group) received both CsA and CoPP intraperitoneally after alloHSCT.Recipients were monitored for condition,survival rate and weight.The liver,small intestine and skin in the recipients were gained and pathological changes of GVHD were assessed.The kidney was stained with Masson staining dye to observe the tissue fibrosis.The expression levels of renal HO-1 mRNA in the recipients were detected.Results In contrast to BS and CsA groups,GVHD degree in combination group was mild,with less reduction and quick recovery of weight.On the day 30 after HSCT,survival rate in BS group was 36.8%,and that in combination group and CsA group was 69.6% and 53.5% respectively (P<0.05).In comparison with BS and CsA groups,pathological changes in combination group were mild,cellular edema and degeneration degree of the liver,small intestine and skin were slight,and few necrosis and infiltrated inflammatory cells were observed.Tubulointerstitial fibrosis hardly occurred in combination group,but it occurred in CsA group abundantly.As compared with BS group,the expression levels of HO-1 mRNA was increased in combination group,while decreased in CsA group (P<0.05).Conclusion CsA combined with CoPP enhanced the protective effect of

  9. 肠道急性移植物抗宿主病黏膜通透性与肠黏膜病理改变的相关性研究%Study on Correlation Between Intestinal Permeability and Morphological Change After Intestinal Acute Graft- versus -host Disease In Mice

    Institute of Scientific and Technical Information of China (English)

    蔡芳芳; 庄强; 朱融和; 梁彬; 俞康; 江松福

    2012-01-01

    目的 研究肠道急性移植物抗宿主病( aGVHD)黏膜通透性变化与肠黏膜病理改变以及二者之间的关系.方法 32只BALB/C小鼠随机分为4组:单纯照射组(对照组)和3个时段aGVHD组(aGVHD后7、11和15天组),各8只.TBI剂量8.0Gy,剂量率1.0Gy/min.高效液相色谱-蒸发光散射检测器分析(HPLC - ELSD)检测尿液标本中乳果糖(lactulose,L)和甘露醇( mannitol,M)的排出率比值(L/M),评价各组小鼠的肠道通透性;收集空肠组织标本做病理评估.结果 肠道aGVHD后7、11和15天组L/M比值均明显高于对照组(P<0.05),分别为0.509±0.353,0.717±0.012,0.762±0.014,0.291±0.053.aGVHD 后7、11和15天组aGVHD严重程度评分较对照组显著增加(P<0.05),分别为0.810±0.259,1.940±0.176,2.750±0.267,0.000±0.000.各组L/M与肠道aGVHD严重程度水平呈显著相关(r=0.903,P<0.01).结论 aGVHD后随着时间延长肠黏膜通透性逐渐增加且肠道aGVHD严重程度评分逐渐增高;aGVHD后肠道通透性与肠道aGVHD严重程度呈显著相关,尿液L/M可作为肠道aGVHD严重程度的无创评估方法.%To investigate the change of the intestinal permeability and the morphology, and study the relationship between them after intestinal acute graft - versus - host disease(aGVHD) in mice. Methods BALB/C mice were randomly divided into 4 groups; 3 aGVHD groups (7 day, 11 day and 15 day after aGVHD) and the control group, and each group had 8 mice. Total body irradiation was: dosage 8.0Gy, doBe rate 1.0Gy/min. High -performance liquid chromatography evaporative light -scattering detector ( HPLC-ELSD) by using two -sugar absorption test for evaluating the intestinal permeability was developed. Urine mannitol/lactulose (L/M) excretion ratios were measured, Jejunum tissues were collected, and the degree of pathology of aGVHD was analysed. Results The urine L/M ratio was significantly increased in aGVHD groups (0. 509 ?. 353,0.717 ?.012,0.762 ?.014) than the control (0. 291

  10. TLR5激动剂鞭毛蛋白预防小鼠异基因造血干细胞移植后急性移植物抗宿主病的初步研究%Prophylactic Effect of TLR5 Agonist Flagellin on Acute Graft versus Host Disease after Allogeneic Hematopietic Stem Cell Transplantation and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    龚旭东; 马梁明; 朱镭; 郭慧敏; 任连生; 任瑞瑞; 张华屏; 卫芬; 牛燕燕

    2012-01-01

    本研究旨在探讨Toll样受体(TLR5)激动剂鞭毛蛋白(flagellin)对小鼠异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(aGVHD)的预防作用和可能作用机制.用主要组织相容性抗原完全不合的纯种近交系小鼠[供体鼠:雄性C57BL/6鼠;受体鼠:雌性BALB/c鼠]建立allo-HSCT的aGVHD动物模型.受鼠随机分为3组:鞭毛蛋白组,于移植前后2次尾静脉注射高纯度(纯度≥95%)的鞭毛蛋白50μl[5μg/(只·次)]预防aGVHD;单纯移植组,移植后仅给予等容量PBS;单纯照射组,仅照射不移植,亦给予等容量PBS.观察比较移植后aGVHD的表现.结果表明,移植小鼠均出现典型的aGVHD症状,单纯移植组小鼠死亡高峰在移植后第4-5天.用鞭毛蛋白作为aGVHD预防方案小鼠的aGVHD症状明显减轻,平均生存时间较单纯移植组显著延长(P<0.05).三组小鼠移植前外周血白细胞数比较均无显著性差异,但在照射后第14、21天,鞭毛蛋白组较单纯移植组外周血白细胞数显著性升高(P<0.05).鞭毛蛋白预防组移植小鼠aGVHD病理表现较单纯移植组明显减轻.流式细胞仪检测鞭毛蛋白组与单纯移植组移植前后不同时间点Treg细胞/CD4+T细胞含量结果也表明,移植后2-4周鞭毛蛋白组小鼠的Treg细胞数较单纯移植组明显增加(P<0.05).结论:鞭毛蛋白对小鼠allo-HSCT后发生aGVHD有预防作用,能减轻其症状和病理损害程度,显著延长其平均生存时间,其机制有可能通过增加移植后小鼠的Treg细胞含量,从而有效改善并减轻移植后小鼠aGVHD.%This study was aimed to investigate the prophylactic effect of Toll like receptor (TLR)5 agonist flagellin on acute graft versus host disease (aGVHD) after allogeneic hematopietic stem cell transplantation (allo-HSCT) and its possible mechemism. The animal model with allo-HSCT aGVHD was established by using purebreed mice (male mouse C57BL/6 as donor, femal mouse BALB/c as recipient

  11. Association between acute graft versus host disease and lung injury after allogenic hematopoietic stem cell transplantation%异基因造血干细胞移植后急性移植物抗宿主病与肺损伤的关系

    Institute of Scientific and Technical Information of China (English)

    刘启发; 罗晓丹; 范志平; 宁涓; 徐丹; 孙竞; 张钰; 徐兵; 魏永强

    2009-01-01

    Objective To investigate the characteristics of chest hiigh-resolution computed tomography(HRCT)and pathogenesis of acute graft versus host disease(aGVHD)-induced lung injury after allogenic hematopoietic stem cell transplantation(allo-HSCT).Methods Chest HRCT was performed in 47 patients with aGVHD of grade Ⅱ-Ⅳ after allo-HSCT.Twenty-four of the patients underwent different treatment regimens against aGVHD.Before the treatment peripheral blood samples were collected to detect the serum interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α).Transbronchial biopsy was performed in 4 patients that failed to recover completely after treatment.Pulmonary function was examined in the patients who survived more than 6 months in every 3 months.Resuits Twenty of tlle 47 patients showed abnormal images by chest HRCT and 17 of the 20 patients were suspected to be witll aGVHD-induced lung iniury.The HRCT images were characterized by diffused interstitial infiltrate in 5 cases.diflused intemtitial and alveolar infiltrate in 7 cases.and diffused interstitial and segmental lobar alveolar infiltrate in 5 cases.Nine cases had bilateral pleural effusion and hydropericardium,including 4 eases accompanied by myocardial hypertrophy.The levels of serum IFN-γ and TNF-α of the patients with lung injury were(6.9±1.8)μg/L and(400±102)μg/L respectively,both not significantly different from those of the patients without lung injury[(6.3±1.2)μg/L and(428±83)μg/L respectively,P=0.202,0.306].The histopathology of the lung tissue was characterized by disorganization,epithelial cell damage,interstitial fibroplasias,and interstitial T lymphocyte or macrophage infiltrate.The effective rate of treatment for aGVHD-induced lung iniury was positively correlated witll that for aGVHD(r=0.771,P=0.01).Eleven of the 24 patients who survived more than 6 months had abnormal pulmonary function.including 7 out of tlle 9 patients with aGVHD-induced lung injury and 4 out the 15 patients without a

  12. Relationship between graft-versus-host disease and endothelium injury following hematopoietic stem cells transplantation in mice%小鼠造血干细胞移植后移植物抗宿主病与内皮细胞损伤的关系

    Institute of Scientific and Technical Information of China (English)

    闫志凌; 贾路; 许世娟; 徐开林; 潘彬; 宋国梁; 陈翀; 曾令宇

    2010-01-01

    Objective To study the relationship between graft-versus-host disease (GVHD) and endothelium injury following hematopoietic stem cells transplantation in mice. Methods C57BL/6 mice as donors and Balb/c mice as recipients were randomly divided into 4 groups: control group, bone marrow transplantation group, GVHD group, GVHD mitigation group. The clinical manifestations,circulating endothelial cells and tissue pathological changes were observed at different time points after transplantation. Results No manifestations of GVHD were found in each group at the day 5, while those were found in GVHD group at the day 9 and all died within 15 days. The counts of endothelial cells in peripheral blood showed no significant difference at the day 5 between GVHD group (7. 34 ±1.26 cells/μl) and bone marrow transplantation group (11.51 ± 7. 40 cells/μl) or GVHD mitigation group (7. 36 ± 0. 16 cells/μl), while among three groups there was statistically significant difference at the day 9 (GVHD group: 153. 64 ± 35. 35 cells/μl vs bone marrow transplantation group: 10. 49 ±5. 61 cells/μl and GVHD mitigation group: 47. 82 ± 4. 69 cells/μl). The scores of pathological aGVHD had no significant difference at the day 5 between GVHD group (4. 33± 1. 53) and bone marrow transplantation group (3. 33 ± 0. 58) or GVHD mitigation group (4. 00 ± 1.73), while among three groups there was statistically significant difference at the day 9 (GVHD group: 10. 0 vs bone marrow transplantation group: 3. 33 ± 1.15 or GVHD mitigation group: 4. 33 ± 0. 58) and at the day 14 (GVHD group: 10. 33 ± 2. 58 vs bone marrow transplantation group: 2. 33 ± 1.25 or GVHD mitigation group 3. 33 ± 1.15). Conclusion Occurrence of GVHD causes endothelial damage again and injured endothelium worsens the GVHD.%目的 探讨异基因造血干细胞移植后移植物抗宿主病(GVHD)与内皮细胞损伤的关系.方法 以C57BL/6小鼠为供者、Balb/c小鼠为受者,分4组进行异基因造

  13. Expression and significance of CD4+ CD25+ Foxp3+ T cells in the acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation%骨髓或外周血中CD4+CD25+Foxp3+调节性T淋巴细胞与aGVHD的关系

    Institute of Scientific and Technical Information of China (English)

    王晓娟; 车传珍; 周昱男; 刘仲萍; 黄士昂

    2009-01-01

    目的 研究患者异基因造血干细胞移植(allo-HSCT)前后骨髓或外周血单个核细胞中CD4+CD25+Foxp3+调节性T淋巴细胞(以下简称CD4+CD25+Foxp3+T细胞)的比率、Foxp3 mRNA和Foxp3蛋白的表达与急性移植物抗宿主病(aGVHD)的关系.方法 选择37例行HIA相合异基因造血干细胞移植(allo-HSCT))的患者作为研究对象.采用流式细胞术检测患者allo-HSCT前7天(-7 d)、移植当天(0 d)、移植后30天(+30d)、+60 d和+90 d时骨髓或外周血单个核细胞中CD4+CD25+Foxp3+T细胞所占的比率;定量聚合酶链反应(PCR)检测Foxp3 mRNA相对表达量;蛋白印迹(Western blot)法检测Foxp3的蛋白表达水平.结果 37例患者存移植后100 d内发生aGVHD 13例(aGVHD组),未发生aGVHD 24例(无aGVHD组).CD4+CD25+Foxp3+T细胞的比率在0 d时最低,与-7、+30、+60、+90d时比较.差异均有统计学意义(P<0.01);与aGVHD组比较,无aGVHD组患者的CD4+CD25+Foxp3+T细胞的比率明显升高,差异有统计学意义(P<0.01).aGVHD组患者移植后Foxp3的表达水平逐渐升高,但明显低于无aGVHD组,尤其在+60和+90 d时的差异有统计学意义(P<0.01).Western blot法检测结果 表明,aGVHD组受者的Foxp3蛋白表达也明显低于无aGVHD组.结论 CD4+CD25+Foxp3+T细胞对防止发生aGVHD具有重要作用,监测患者骨髓或外周血中CD4+CD25+Foxp3+T细胞的比率可以预测aGVHD的发生.%Objective To investigate the expression and significance of CD4+ CD25+ Foxp3+ T Cells, Foxp3 mRNA and Foxp3 protein in the acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Thirty-seven donor grafts and their respective clinical characteristics were evaluated. Flow cytometric analysis was performed to assess the percentage of CD4+ CD25+ Foxp3+ T cells in the recipients before, and 0, 30, 60, and 90 days after allo-HSCT. The relative expression of Foxp3 mRNA was detected by real time reverse transcription-polymerase chain

  14. Preliminary study on IL-7Rα intervening acute graft-versus-host disease after mice allogeneic bone marrow transplantation%白细胞介素7受体α干预小鼠异基因骨髓移植后急性移植物抗宿主病的初步研究

    Institute of Scientific and Technical Information of China (English)

    卫芬; 马梁明; 龚旭东; 任连生; 朱镭; 郭慧敏; 张华屏

    2013-01-01

    Objective To establish a mouse model of acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation,and using exogenous interleukin-7 receptor alpha (IL-7Rα) intervene mice aGVHD and analyse its possible mechanism.Methods The BALB/C (H-2d) female mice as recipients were grouped by rat: the irradiation group (group A),irradiation transplantation group (group B) and IL-7Rα in the intervention group (group C),each 10.ALL mice were accepted 9 Gy60Co total body irradiation.1×107 bone marrow cells and 2×107 spleen cells of donor C57BL/6 (H-2b) via the tail vein were infused to recipient mice.The signs of the recipient mice,hematopoietic functional recovery and survival time of change,and pathology,chimerism and cytokine levels in checkwere observed.Results Mice in A group after irradiation were gradually death,in group B and group C mice after transplantation had typical aGVHD symptoms,but lighter signs and a longer survival time of Group C than in group B.WBC count in Group C was +14 d (4.53± 0.21) ×109/L,+21 d (3.63±0.06) ×109/L,+28 d (4.31±0.04) ×109/L,was hematopoietic recovery compared with Group B [+14 d (1.81±0.05) ×109/L,+21 d (1.32±0.04) ×109/L,+28 d (1.76±0.04) ×109/L],the difference was statistically significant (t =0.237,0.108,0.359,P < 0.05).The pathological results of liver,spleen,skin histopathology in group C were better than group B.Chimera implants,plasma IL-7 levels after transplant +7 d,concentration was significantly increased.IL-7 concentration in group C was +14 d (194.32±1.02) pg/ml,+21 d (131.63±1.54) pg/ml and in group B was +14 d (330.24±8.08) pg/ml,+21 d (184.09±2.05) pg/ml,the difference was statistically significant (t =1.590,1.285,P <0.05).Conclusion The stable aGVHD mouse model was established.In aGVHD early,plasma IL-7 levels were significantly increased.Exogenous IL-7Rαcan reduce the plasma IL-7 levels,thereby reducing the incidence of aGVHD after allogeneic bone marrow transplantation

  15. Enhancement of the graft-versus-host reaction by radio- and chemotherapy

    International Nuclear Information System (INIS)

    An experimental model has been developed to study the interaction of the Graft-versus- Host (GvH) reaction with damage induced by radiation or cytotoxic drugs. In this model the GvH reaction is induced in hybrid mice by injection of parental lymphoid cells. Partial body irradiation prior to injection of parental cells enhances the severity of the GvH reaction. This response is manifest as an increased mortality and decreased survival time in mice given combined GvHD/radiation treatment compared with mice given radiation or lymphoid cells only. There is also a synergistic increase in the extent of GvHD-induced immunosuppression in mice given combined treatment. The degree of enhancement of the GvH reaction was related to radiation dose and the size of the radiation field. The GvH response was also found to be enhanced by Cyclophosphamide when the drug was injected prior to GvHD induction

  16. 异基因造血干细胞移植受者外周血单核细胞趋化蛋白-2和IL-12水平变化与急性移植物抗宿主病的相关性%Chan ges of monocyte chemoattractant protein-2 and IL-12 levels in peripheral blood of recipients of allogeneic hemapoietic stem cell transplantation and their correlation with acute graft versus host disease

    Institute of Scientific and Technical Information of China (English)

    费晓莉; 刘林

    2012-01-01

    Objective To investigate the changes of monocyte chemoattractant protein-2 / C-C motif ligand 8 ( MCP-2 / CCL8 ) and IL-12 levels in peripheral blood of recipients of allogeneic hemapoietic stem cell transplantation (allo-HSCT) as well as their correlation with acute graft versus host disease (aGVHD), and provide reliable indexes for early diagnosis of aGVHD in clinic. Methods Twenty recipients of allo-HSCT were served as trial group, while those of autoplastic HSCT as control group. The MCP-2 and IL-12 levels in sera were determined 14(before pre-treatment) and 1 d(after pre-treatment and before stem cell reinfusion) before transplantation, and once a week after transplantation for 8 weeks, while those of patients with aGVHD were determined twice a week after appearance of clinical symptoms. Results In both trial and control groups, no significant differences were observed between the MCP-2 and IL-12 levels in sera 14 and 1 d before transplantation (P > 0. 05), or between those 7 after and 1 d before transplantation (P > 0. 05). Six cases of aGVHD were observed in trial group, of which clinical symptoms appeared 16 ~ 52 d after transplantation, and the time when serum MCP-2 and IL-12 levels increased firstly as compared with those 7 d after transplantation was earlier than that when the clinical symptoms appeared. The serum MCP-2 and IL-12 levels of the patients at time of diagnosis increased significantly as compared with those 7 d after transplantation (P 0. 05). Conclusion MCP-2 and IL-12 were correlated with aGVHD, of which the levels changed earlier than the appearance of clinical symptoms. The determination of serum MCP-2 and IL-12 levels was helpful to the early diagnosis of aGVHD.%目的 探讨异基因造血干细胞移植(allogeneic hemapoietic stem cell transplantation,allo-HSCT)受者外周血单核细胞趋化蛋白-2(Monocyte chemoattractant protein-2/C-C motif ligand 8,MCP-2/CCL8)和白细胞介素- 12( Interleukin- 12,IL-12)水平变化与

  17. Analysis of DNA methylation with 5-Azac induced immune hyporesponsiveness following acute graft-versus-host disease%5-Azac诱导急性移植物抗宿主病免疫低反应的甲基化研究

    Institute of Scientific and Technical Information of China (English)

    张晓宁; 赵玉霞; 王建海; 苗绪红; 李克秋; 李光

    2016-01-01

    目的 建立小鼠急性移植物抗宿主病(aGVHD)模型,检测DNA甲基化转移酶抑制剂5-氮杂胞苷(5-aza-cytidine,5-Azac)诱导aGVHD免疫低反应后的甲基化变化,探讨5-Azac对小鼠aGVHD的免疫调节作用.方法 选择雄性C57BL/6(H-2b)与雌性BALB/c(H-2d)小鼠分别作为异基因移植供、受体建立移植物抗宿主病小鼠模型.BABL/c受体按照体质量相近进行配对,分为移植对照组和5-Azac实验组.5-Azac实验组于移植后1~7、14、21、28 d尾静脉注射5-Azac 0.25 mg/kg(0.3 mL/只);移植对照组尾静脉注射生理盐水0.3 mL/只.提取3只移植对照组和3只5-Azac实验组小鼠的外周血DNA,分别等量混匀,采用甲基化DNA免疫共沉淀测序(MeDIP-seq)的方法检测甲基化变化,筛选差异甲基化基因,并对其功能及生物学通路进行分析.结果 5-Azac实验组小鼠的生存时间延长,排斥反应减弱,成功诱导移植物抗宿主病免疫低反应状态.2组小鼠DNA MeDIP-seq结果对比显示:5-Azac实验组启动子区存在369个差异甲基化基因,其中上调239个、下调130个;外显子区存在184个差异甲基化基因,其中上调113个、下调71个.利用KEGG(Kyoto Encyclopedia of Genes and Genomes)数据库对差异甲基化基因分析,结果显示其主要参与10个免疫学信号通路,其中TGF-β、GSK-3β、SYK、PI3K、NFAT、CD28、α4β7与aGVHD的发生发展密切相关.结论 5-Azac可以通过改变基因的甲基化状态有效诱导aGVHD的免疫低反应.%Objective To analyse the change of DNA methylation with 5-Azac injection in acute graft-versus-host dis- ease (aGVHD) mouse model, which received allogeneic bone marrow transplantation, and explore the immunomodulatory ef-fects of 5-Azac. Methods Male C57BL/6 (H-2b)and female BALB/c (H-2d) mice were selected as donor and recipient of complete allotransplantation. BABL/c mice were divided into two groups, transplantation control group and 5-Azac experi-mental group. At 1-7, 14, 21

  18. Prediction of graft-versus-host disease in humans by donor gene-expression profiling.

    OpenAIRE

    Chantal Baron; Roland Somogyi; Greller, Larry D.; Vincent Rineau; Peter Wilkinson; Cho, Carolyn R; Mark J Cameron; Kelvin, David J.; Pierre Chagnon; Denis-Claude Roy; Lambert Busque; Rafick-Pierre Sékaly; Claude Perreault

    2007-01-01

    Editors' Summary Background. Human blood contains red blood cells, white blood cells, and platelets, which carry oxygen throughout the body, fight infections, and help blood clot, respectively. Normally, blood-forming (hematopoietic) stem cells in the bone marrow (and their offspring, peripheral blood stem cells) continually provide new blood cells. Tumors that arise from the bone marrow (such as leukemia and lymphoma, two types of hematopoietic tumor) are often treated by a bone marrow or pe...

  19. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Storb, Rainer; Gyurkocza, Boglarka; Storer, Barry E;

    2013-01-01

    We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the pures...

  20. HLA-DP and bonemarrow transplantation: DP-incompatibility and severe acute graft versus host disease

    DEFF Research Database (Denmark)

    Ødum, Niels; Platz, P; Jakobsen, B K;

    1987-01-01

    The presence of activated T cells as judged from the reaction with monoclonal antibodies (MoAb) against (a) a late stage T cell activation antigen (VLA-1), (b) the interleukin 2 (IL2) receptor (CD25), and (c) four different HLA class II molecules (HLA-DR, DRw52, DQ, and DP) was studied in 15...... the various HLA class II antigens was observed between the groups. Similarly, no significant differences in stimulatory capability in secondary mixed lymphocyte culture (MLC) were seen. The distribution of T helper/inducer (CD4+), T suppressor/cytotoxic (CD8+), and NK cells was similar in active JCA...

  1. Treatment of pruritic diseases with topical calcineurin inhibitors

    OpenAIRE

    Ständer, Sonja; Schürmeyer-Horst, Funda; Luger, Thomas A; Weisshaar, Elke

    2006-01-01

    The introduction of topical calcineurin inhibitors resulted in a significant improvement in the treatment of atopic dermatitis. In addition, rapid amelioration of pruritus could be observed. In case reports, other pruritic dermatoses such as chronic irritative hand dermatitis, rosacea, graft-versus-host-disease, and lichen sclerosus were also treated successfully with pimecrolimus and tacrolimus. Twenty patients were treated with tacrolimus and pimecrolimus in a surveillance study to evaluate...

  2. Reacción de ingerto versus huésped: de la comprensión a la utilización de un fenómeno biológico Graft versus host reation: from comprehension to utilization of a biological phenomenon

    Directory of Open Access Journals (Sweden)

    Jorge Eliécer Ossa Londoño

    1999-01-01

    Full Text Available La enfermedad de injerto versus huésped es una de las complicaciones con mayor mortalidad que se presentan después de un trasplante, usualmente de médula ósea, o después de una transfusión sanguínea.- Los principales órganos blanco son la piel. el hígado, el tracto gastrointestinal y el sistema inmune. Sin embargo. la apreciación de esta enfermedad ha venido cambiando a medida que avanza la comprensión de la inmunología de trasplantes. pues se ha visto que puede tener resultados benéficos como son un efecto antireucémico y un aumento de la tolerancia a los trasplantes. Graft versus host disease is one of the complications with greater lethality after transplantation, usually of bone marrow, or after blood transfusion. Organs involved include skin, liver, gastrointestinal tract and the immune system. However, the conception of graft versus host disease has been changing as comprehension of transplant immunology has advanced, since it has been demonstrated that it can have beneficial results as an antileucemic response and because of an increased tolerance to grafts.

  3. Outcomes of unrelated cord blood transplantation in patients with multiple myeloma: a survey on behalf of Eurocord, the Cord Blood Committee of Cellular Therapy and Immunobiology Working Party, and the Chronic Leukemia Working Party of the EBMT.

    Science.gov (United States)

    Paviglianiti, Annalisa; Xavier, Erick; Ruggeri, Annalisa; Ceballos, Patrice; Deconinck, Eric; Cornelissen, Jan J; Nguyen-Quoc, Stephanie; Maillard, Natacha; Sanz, Guillermo; Rohrlich, Pierre-Simon; Garderet, Laurent; Volt, Fernanda; Rocha, Vanderson; Kroeger, Nicolaus; Gluckman, Eliane; Fegueux, Nathalie; Mohty, Mohamad

    2016-09-01

    Although allogeneic stem cell transplantation is not a standard therapy for multiple myeloma, some patients can benefit from this intense therapy. There are few reports on outcomes after umbilical cord blood transplantation in multiple myeloma, and investigation of this procedure is warranted. We retrospectively analyzed 95 patients, 85 with multiple myeloma and 10 with plasma cell leukemia, receiving single or double umbilical cord blood transplantation from 2001 to 2013. Median follow up was 41 months. The majority of patients received a reduced intensity conditioning. The cumulative incidence of neutrophil engraftment was 97%±3% at 60 days, and that of 100-day acute graft-versus-host disease grade II-IV was 41%±5%. Chronic graft-versus-host disease at two years was 22%±4%. Relapse and non-relapse mortality was 47%±5% and 29%±5% at three years, respectively. Three-year progression-free survival and overall survival were 24%±5% and 40%±5%, respectively. Anti-thymocyte globulin was associated with decreased incidence of acute graft-versus-host disease, higher non-relapse mortality, decreased overall and progression-free survival. Patients with high cytogenetic risk had higher relapse, and worse overall and progression-free survival. In conclusion, umbilical cord blood transplantation is feasible for multiple myeloma patients.

  4. Disease: H00084 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available bone marrow transplant. Annu Rev Med 54:29-52 (2003) PMID:15931364 (drug) Iwasaki T. Recent advances in the treatment of graft-versus-host disease. Clin Med Res 2:243-52 (2004) ...

  5. [Migration and distribution of allogeneic T lymphocytes in organs of graft-versus-host disease mouse model].

    Science.gov (United States)

    Wen, Hong-Sheng; Wang, Jian-Min; Zhou, Hong; Xia, Rong; Qiu, Hui-Ying; Gao, Lei; Hu, Xiao-Xia

    2006-10-01

    This study was aimed to investigate the migration and distribution processes of allogeneic donor T lymphocytes in the organs of recipient mice. GVHD model was established by transfusion of the splenocytes of eGFP transgeneic C57BL/6 mice together with born marrow cells harvested from C57BL/6 mice into BALB/c mice underwent 8.0 Gy total body irradiation. The migration and homing of eGFP(+) cells were tracked by stereo-fluorescent microscopy or inverted fluorescent microscopy and flow cytometry. The enzyme linked immunosorbent assay (ELISA) was performed on supernatants from the tissue homogenates to detect the amount of MIP-1alpha. The results indicated that GVHD clinical manifestation and pathological changes of organs appeared on day 8 post transplantation. eGFP-positive donor T cells in recipient organs were observed by inverted fluorescence microscope in frozen section, or by stereo-fluorescence microscopy in living organs, such as liver, spleen, skin, lungs, bowels, and tongue. The highest expression of MIP-1alpha was on day 7 post transplantation in the liver (491.3 +/- 32.1 pg/ml), and day 3 post transplantation in the spleen (881.5 +/- 45.2 pg/ml), respectively (P liver, skin, bowels, as well as lungs and tongue. MIP-1alpha may be in relation with the infiltration of T lymphocytes in liver and spleen.

  6. HLA-DP and bone marrow transplantation: DP-incompatibility and severe acute graft versus host disease

    DEFF Research Database (Denmark)

    Ødum, Niels; Platz, P; Jakobsen, B K;

    1987-01-01

    Thirteen recipients of HLA-haploidentical, DR compatible bone marrow (BM) and the corresponding BM donors were HLA-DP typed using primed lymphocyte typing (PLT). Severe acute GVHD (greater than or equal to grade 2) developed within 3 months after BM-transplantation in all of eight recipients of DP...... a role as transplantation antigens....

  7. ECZEMATOID GRAFT VERSUS HOST DISEASE IN A SEX MISMATCHED ALLOGENEIC STEM CELL TRANSPLANT REFRACTORY TO TREATMENT: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Abhilasha

    2014-03-01

    Full Text Available A 25 years old gentleman presented with bleeding gums, purpura and fever for 2 months and severe anemia requiring 10 blood transfusions. Baseline hematological investigations and bone marrow examination confirmed aplastic anemia. He underwent allogeneic stem cell transplant as a curative option with HLA identical sister as the donor. Neutrophils engrafted on day +16. On day +115 he showed signs of dyshydrotic eczema and was initiated on local and systemic steroids and topical tacrolimus. As there were features of Cyclosporin induced MAHA, the same was stopped and oral Mycophenolate was initiated on day +129. On day +170 he presented with extensive progression of cutaneous and hepatic GVHD. Subsequent treatment with Cyclophosphamide, Sirolimus and Daclizumab did not show significant response. On day +195, he succumbed to sepsis with multiorgan failure. The diagnosis of ezcematoid GVHD was confirmed by cutaneous manifestations, biopsy, the clinical course and the presence of GVHD in other organs.

  8. 趋化因子受体CCR5与移植物抗宿主病%Chemokine Receptor-5 and Graft-versus-Host Disease——Review

    Institute of Scientific and Technical Information of China (English)

    袁景; 刘微; 任汉云

    2015-01-01

    趋化因子受体CCR5(CC chemokine receptor 5)是G蛋白偶联受体超家族的一员,主要表达在机体多种免疫细胞表面.CCR5依赖与其特异性配体的结合而发挥生物学作用,在细胞的生长、活化、分化、粘附及定向迁移等方面起着重要作用.CCR5是人免疫缺陷病毒1型(human immunodeficiency virus type-1,HIV-1)入侵人体的重要辅助受体之一,参与病毒与T细胞结合的过程.靶向CCR5的治疗不仅具有抗病毒作用,还具有免疫调节作用.研究发现,CCR5不仅在AIDS、自身免疫病、动脉粥样硬化等疾病的致病机制中起作用,在异基因造血干细胞移植(allo-geneic hematopoietic stem cell transplantation,allo-HSCT)后急性移植物抗宿主病(acute graft versus host disease,aGVHD)发生发展过程中,同样扮演着重要的角色.大量动物实验证实,CCR5及其配体介导了效应T细胞向GVHD靶器官的迁移与募集.因此,本文就CCR5的结构和功能、内化途径、信号转导通路及其与allo-HSCT后aGVHD的关系作一综述.

  9. Chronic GvHD decreases antiviral immune responses in allogeneic BMT

    OpenAIRE

    Hossain, Mohammad S.; Roback, John D.; Pollack, Brian P.; Jaye, David L.; Langston, Amelia; Waller, Edmund K.

    2007-01-01

    Chronic graft-versus-host disease (cGvHD) is associated with functional immunodeficiency and an increased risk of opportunistic infections in allogeneic bone marrow transplantation (BMT). We used a parent to F1 model of allogeneic BMT to test the hypothesis that cGvHD leads to impaired antigen-specific antiviral immunity and compared BM transplant recipients with cGvHD to control groups of allogeneic BM transplant recipients without GvHD. Mice with and without cGvHD received a nonlethal dose ...

  10. Loss of Mismatched HLA on the Leukemic Blasts of Patients With Relapsed Lymphoid Malignancies Following Bone Marrow Transplantation From Related Donors With HLA Class II Mismatches in the Graft Versus Host Direction.

    Science.gov (United States)

    Hirabayashi, Koichi; Kurata, Takashi; Horiuchi, Kazuki; Saito, Shoji; Shigemura, Tomonari; Tanaka, Miyuki; Yanagisawa, Ryu; Matsuda, Kazuyuki; Sakashita, Kazuo; Koike, Kenichi; Nakazawa, Yozo

    2016-04-01

    Mechanisms of relapse of acute lymphoblastic leukemia (ALL) after human leukocyte antigen (HLA) class II mismatched hematopoietic stem cell transplantation (HSCT) remain unclear. We report two children with relapsed ALL after HSCT from related donors with HLA-DRB1 and -DQB1 mismatches in the graft versus host direction. One lost HLA-DRB1, DQB1, and DPB1 alleles, and the other lost one HLA haplotype of the leukemic blasts at relapse. HLA class II loss may be a triggering event for ALL relapse after partially HLA-mismatched-related HSCT. In addition, HLA typing of relapsed leukemic blasts could be vital in the selection of retransplant donors. PMID:26544669

  11. Dry Eye Disease Incidence Associated with Chronic Graft-Host Disease: Nonconcurrent Cohort Study (An American Ophthalmological Society Thesis)

    Science.gov (United States)

    Mian, Shahzad I.; De la Parra-Colín, Paola; De Melo-Franco, Rafael; Johnson, Christopher; Barrientos-Gutierrez, Tonatiuh

    2015-01-01

    Purpose: To determine if chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with stable or progressive dry eye disease and to determine the true incidence in patients with no prior history of dry eye disease. Methods: A nonconcurrent cohort study at a single institution with 136 patients who had no previous history of dry eye disease before HSCT. Survival analysis was used to estimate dry eye disease incidence. The incidence rate was calculated using life tables as the number of observed dry eye disease cases divided by the person-time at risk accumulated by the cohort. Transition probabilities were calculated from time of transplant to time of diagnosis, and then to last recorded visit. Results: Incidence rate was 0.8 cases of dry eye disease per person-year, and half of the population at risk developed dry eye disease during the first 10 months post transplant. Time to develop dry eye disease was 2.5 months for mild dry eye disease, 9.6 months for moderate dry eye disease, and 13.2 months for severe dry eye disease. In terms of cumulative incidence, 73% of subjects developed dry eye disease (50% mild, 16% moderate, and 7% severe) at the time of diagnosis. Conclusions: Our findings suggest that dry eye disease associated with cGVHD is an extremely frequent event and shows a wide spectrum of severity, with a mild form presenting early and a moderate to severe form presenting later after HSCT. These findings need to be studied further to elucidate if these are two different pathophysiological entities or just different expressions of the same pathology. PMID:27507907

  12. Stem cell therapy in treatment of different diseases.

    Science.gov (United States)

    Larijani, Bagher; Esfahani, Ensieh Nasli; Amini, Peyvand; Nikbin, Behrouz; Alimoghaddam, Kamran; Amiri, Somayeh; Malekzadeh, Reza; Yazdi, Nika Mojahed; Ghodsi, Maryam; Dowlati, Yahya; Sahraian, Mohammad Ali; Ghavamzadeh, Ardeshir

    2012-01-01

    Stem cells are undifferentiated cells with the ability of proliferation, regeneration, conversion to differentiated cells and producing various tissues. Stem cells are divided into two categories of embryonic and adult. In another categorization stem cells are divided to Totipotent, Multipotent and Unipotent cells.So far usage of stem cells in treatment of various blood diseases has been studied (such as lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple myeloma and cycle cell anemia). In this paper the goal is evaluation of cell therapy in treatment of Parkinson's disease, Amyotrophic lateral sclerosis, Alzheimer, Stroke, Spinal Cord Injury, Multiple Sclerosis, Radiation Induced Intestinal Injury, Inflammatory Bowel Disease, Liver Disease, Duchenne Muscular Dystrophy, Diabetes, Heart Disease, Bone Disease, Renal Disease, Chronic Wounds, Graft-Versus-Host Disease, Sepsis and Respiratory diseases. It should be mentioned that some disease that are the target of cell therapy are discussed in this article.

  13. Stem Cell Therapy in Treatment of Different Diseases

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Sahraian

    2012-02-01

    Full Text Available Stem cells are undifferentiated cells with the ability of proliferation, regeneration, conversion to differentiated cells and producing various tissues. Stem cells are divided into two categories of embryonic and adult. In another categorization stem cells are divided to Totipotent, Multipotent and Unipotent cells.So far usage of stem cells in treatment of various blood diseases has been studied (such as lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple myeloma and cycle cell anemia. In this paper the goal is evaluation of cell therapy in treatment of Parkinsons disease, Amyotrophic lateral sclerosis, Alzheimer, Stroke, Spinal Cord Injury, Multiple Sclerosis, Radiation Induced Intestinal Injury, Inflammatory Bowel Disease, Liver Disease, Duchenne Muscular Dystrophy, Diabetes, Heart Disease, Bone Disease, Renal Disease, Chronic Wounds, Graft-Versus-Host Disease, Sepsis and Respiratory diseases. It should be mentioned that some disease that are the target of cell therapy are discussed in this article.

  14. Impact of Inflammatory Cytokine Gene Polymorphisms on Developing Acute Graft-versus-Host Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Riccardo Masetti

    2015-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs in gene encoding pro- and anti-inflammatory factors have been associated with the occurrence of aGvHD. We retrospectively tested a wide panel of 38 polymorphisms in 19 immunoregulatory genes, aiming to first establish, in a pediatric HSCT setting, which SNPs were significantly associated with the development of aGvHD. A significant association was found between aGvHD grades II–IV and SNPs of donor IL10-1082GG, and Fas-670CC + CT and recipient IL18-607 TT + TG genotype. aGvHD grades III-IV resulted associated with donor IL10-1082GG, Fas-670CC + CT, and TLR4-3612TT as well as the use of peripheral CD34+ cells as stem cell source. The multivariate analysis confirmed the association between donor IL10-1082GG and Fas-670CC + CT and aGvHD grades II–IV and between donor IL10-1082GG and TLR4-3612TT and aGvHD grades III-IV. In conclusion we found an association between IL10, FAS, and TLR4 in the donor and IL18 in the recipient and an increased risk of developing aGvHD in transplanted children. Knowledge of the SNPs of cytokine genes associated with aGvHD represents a useful tool for an integrated pretransplantation risk assessment and could guide the physicians to an optimal and more accurate HSCT planning.

  15. Impact of Cytomegalovirus and Grafts versus Host Disease on the Dynamics of CD57+CD28−CD8+ T Cells After Bone Marrow Transplant

    OpenAIRE

    Ana Verena Almeida Mendes; Esper Georges Kallas; Gil Benard; Cláudio Sérgio Pannuti; Reneé Menezes; Frederico Luiz Dulley; Thomas George Evans; Reinaldo Salomão; Clarisse Martins Machado

    2008-01-01

    OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with c...

  16. T-cell chimerism is valuable in predicting early mortality in steroid-resistant acute graft-versus-host disease after myeloablative allogeneic cell transplantation

    DEFF Research Database (Denmark)

    Minculescu, Lia; Madsen, Hans O.; Sengeløv, Henrik

    2014-01-01

    different in patients with complete DC versus MC [53 days (range 12–183) vs. 238 days (range 135– 550), p = 0.005]. Conditioning with Etopophos/total body irradiation (TBI) resulted in significantly more patients with MC compared to conditioning with cyclophosphamide/TBI. In conclusion, early complete T...

  17. CC chemokine receptor 8 potentiates donor Treg survival and is critical for the prevention of murine graft-versus-host disease

    OpenAIRE

    Coghill, James M.; Fowler, Kenneth A.; West, Michelle L.; Fulton, LeShara M; van Deventer, Hendrik; McKinnon, Karen P.; Vincent, Benjamin G; Lin, Kaifeng; Panoskaltsis-Mortari, Angela; Cook, Donald N.; Blazar, Bruce R.; Serody, Jonathan S.

    2013-01-01

    Extended donor Treg survival is required for protection from GVHD; donor Treg longevity depends on Treg CCR8 expression.Donor CD11c+ APCs promote Treg longevity in vivo; host CD11c+ APCs do not appear to contribute to donor Treg reconstitution.

  18. A radio-resistant perforin-expressing lymphoid population controls allogeneic T cell engraftment, activation, and onset of graft-versus-host disease in mice.

    Science.gov (United States)

    Davis, Joanne E; Harvey, Michael; Gherardin, Nicholas A; Koldej, Rachel; Huntington, Nicholas; Neeson, Paul; Trapani, Joseph A; Ritchie, David S

    2015-02-01

    Immunosuppressive pretransplantation conditioning is essential for donor cell engraftment in allogeneic bone marrow transplantation (BMT). The role of residual postconditioning recipient immunity in determining engraftment is poorly understood. We examined the role of recipient perforin in the kinetics of donor cell engraftment. MHC-mismatched BMT mouse models demonstrated that both the rate and proportion of donor lymphoid cell engraftment and expansion of effector memory donor T cells in both spleen and BM were significantly increased within 5 to 7 days post-BMT in perforin-deficient (pfn(-/-)) recipients, compared with wild-type. In wild-type recipients, depletion of natural killer (NK) cells before BMT enhanced donor lymphoid cell engraftment to that seen in pfn(-/-) recipients. This demonstrated that a perforin-dependent, NK-mediated, host-versus-graft (HVG) effect limits the rate of donor engraftment and T cell activation. Radiation-resistant natural killer T (NKT) cells survived in the BM of lethally irradiated mice and may drive NK cell activation, resulting in the HVG effect. Furthermore, reduced pretransplant irradiation doses in pfn(-/-) recipients permitted long-term donor lymphoid cell engraftment. These findings suggest that suppression of perforin activity or selective depletion of recipient NK cells before BMT could be used to improve donor stem cell engraftment, in turn allowing for the reduction of pretransplant conditioning.

  19. Chronic obstructive pulmonary disease

    Science.gov (United States)

    ... airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... a protein called alpha-1 antitrypsin can develop emphysema. Other risk factors for COPD are: Exposure to ...

  20. Topical tacrolimus and periodontal therapy in the management of a case of oral chronic GVHD characterized by specific gingival localization.

    Science.gov (United States)

    Conrotto, Davide; Broccoletti, Roberto; Carcieri, Paola; Giaccone, Luisa; Arduino, Paolo G

    2014-01-01

    Background. Chronic graft versus host disease (cGVHD) is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

  1. Topical Tacrolimus and Periodontal Therapy in the Management of a Case of Oral Chronic GVHD Characterized by Specific Gingival Localization

    Directory of Open Access Journals (Sweden)

    Davide Conrotto

    2014-01-01

    Full Text Available Background. Chronic graft versus host disease (cGVHD is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

  2. Role of mobile passenger lymphocytes in the rejection of renal and cardiac allografts in the rat. A passenger lymphocyte-mediated graft-versus-host reaction amplifies the host response

    Energy Technology Data Exchange (ETDEWEB)

    van Vrieshilfgaarde, R.; Hermans, P.; Terpstra, J.L.; van Breda Viresman, P.J.

    1980-03-01

    It is demonstrated that passenger lymphocytes migrate out of rat renal allografts into host spleens in a radioresistant fashion. These mobile passenger lymphocytes within BN kidney and heart transplants are immunocompetent, since they elicit a graft-versus-host (GVH) reaction in the spleens of (LEW x BN)F2 hybrid hosts. The greater GVH reaction in (LEW x BN)F1 recipients of BN kidneys reflects the greater number of mobile passenger lymphocytes in the kidney when compared to the heart. The mobile passenger lymphocytes within BN renal allografts also cause a proliferative response in the spleens of the LEW hosts as well as an accelerated rejection of BN renal allografts when compared to BN cardiac allografts, for the differences between BN kidney and heart, both in terms of splenomegaly elicited in LEW as well as tempo of rejection, are abolished by total body x-irradiation of the donor with 900 rad. Results indicate that a mobile passenger lymphocyte mediated GVH reaction in the central lymphoid organs of the host augments the host response to allogenic kidneys and contributes materially to first-set renal allograft rejection; this GVH reaction on the other hand is not conspicuously present in LEW recipients of BN cardiac allografts and has therefore little effect on first-set cardiac allograft rejection.

  3. Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience.

    Science.gov (United States)

    Morillo-Gutierrez, Beatriz; Beier, Rita; Rao, Kanchan; Burroughs, Lauri; Schulz, Ansgar; Ewins, Anna-Maria; Gibson, Brenda; Sedlacek, Petr; Krol, Ladislav; Strahm, Brigitte; Zaidman, Irina; Kalwak, Krzysztof; Talano, Julie-An; Woolfrey, Ann; Fraser, Chris; Meyts, Isabelle; Müller, Ingo; Wachowiak, Jacek; Bernardo, Maria Ester; Veys, Paul; Sykora, Karl-Walter; Gennery, Andrew R; Slatter, Mary

    2016-07-21

    Chronic granulomatous disease (CGD) can be cured by allogeneic hemopoietic stem cell transplantation (HSCT). Complications include graft failure, graft-versus-host disease (GVHD), infection, and transplant-related mortality; therefore, reduced-intensity conditioning regimens are being used to improve outcomes. In this retrospective study, the aim was to determine the outcome of treosulfan-based conditioning in HSCT for pediatric patients with CGD. The following data were collected: risk features pre-HSCT, additional conditioning agents, donor type and stem cell source, toxicity, engraftment, GVHD, chimerism, viral reactivation, post-HSCT complications, length of follow-up, and outcome. Seventy patients (median age, 107 months; interquartile range [IQR], 46-232 months) from 16 centers worldwide were transplanted between 2006 and 2015. Ninety-one percent had high-risk features. Fifty-seven HLA-matched donors, 12 HLA-mismatched donors, and 1 CD3(+)TCR αβ/CD19 depleted parental haploidentical transplants were performed. No major toxicity was reported. Median times to neutrophil and platelet engraftment were 17 (IQR, 15-35) and 16 (IQR, 13-50) days. At a median follow-up of 34 months (IQR, 13-102 months), the overall survival was 91.4%, and event-free survival was 81.4%. The cumulative incidence of acute grade III-IV GVHD was 12%. Nine patients developed chronic GVHD. When split cell chimerism was available, 95% or more myeloid donor chimerism was documented in 80% of surviving patients. Secondary graft failure occurred in 12% of patients. Treosulfan-containing conditioning regimens can be used safely in HSCT for children with CGD and high-risk clinical features, achieving excellent survival with high myeloid chimerism. Further studies are needed to compare with other regimens and evaluate the long-term outcome, particularly on fertility. PMID:27216217

  4. "Chronic Lyme Disease"

    Science.gov (United States)

    ... Content Marketing Share this: Main Content Area "Chronic Lyme Disease" What is "chronic Lyme disease?" Lyme disease is an infection caused by ... J Med 357:1422-30, 2008). How is Lyme disease treated? For early Lyme disease, a short ...

  5. Chronic kidney disease

    Science.gov (United States)

    Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure ... 2012_CKD_GL.pdf . McCullough PA. Interface between renal disease ... patients with kidney failure. N Engl J Med . 2010;362(14):1312- ...

  6. Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

    Science.gov (United States)

    2005-06-23

    Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

  7. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Luca Laurenti

    2010-08-01

    Full Text Available Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment. Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%: A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity. The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients. Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

  8. Chronic diseases in adolescence

    Directory of Open Access Journals (Sweden)

    Rončević Nevenka

    2006-01-01

    Full Text Available Introduction. The prevalence of chronic diseases in adolescence is constantly increasing, especially in the last two decades. Adolescence is a period of important changes: body growth and development, sexual development, development of cognitive abilities, change in family relations and between peers, formation of personal identity and personal system of values, making decisions on future occupation etc. Chronic diseases in adolescence. Chronic disorders affect all development issues and represent an additional burden for adolescents. The interaction between chronic disorders and various development issues is complex and two-way: the disease may affect development, and development may affect the disease. Developmental, psychosocial and family factors are of great importance in the treatment of adolescents with chronic disorders. Chronic disorders affect all aspects of adolescent life, including relations with peers, school, nutrition, learning, traveling, entertainment, choice of occupation, plans for the future. Physicians should keep in mind that chronic diseases and their treatment represent only one aspect of person's life. Adolescents with chronic diseases have other needs as well, personal priorities, social roles and they expect these needs to be recognized and respected. Adolescent health care should be adjusted to the life style of adolescents.

  9. Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant

    Science.gov (United States)

    2016-02-29

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Graft Versus Host Disease; Hodgkin Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; Waldenstrom Macroglobulinemia

  10. Chronic obstructive pulmonary disease

    OpenAIRE

    NR Anthonisen

    2007-01-01

    The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are...

  11. Sleep and Chronic Disease

    Science.gov (United States)

    ... message, please visit this page: About CDC.gov . Sleep About Us About Sleep Key Sleep Disorders Sleep ... Sheets Data & Statistics Projects and Partners Resources Events Sleep and Chronic Disease Recommend on Facebook Tweet Share ...

  12. Chronic Kidney Disease

    Science.gov (United States)

    You have two kidneys, each about the size of your fist. Their main job is to filter wastes and excess water out of ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...

  13. Mesenchymal stem cells and inflammatory lung diseases.

    Science.gov (United States)

    Iyer, S S; Co, C; Rojas, M

    2009-03-01

    Mesenchymal stem cells (MSCs) are emerging as a therapeutic modality in various inflammatory disease states. A number of ongoing randomized Phase I/II clinical trials are evaluating the effects of allogeneic MSC infusion in patients with multiple sclerosis, graft-versus-host disease, Crohn's disease, and severe chronic myocardial ischemia. MSCs are also being considered as a potential therapy in patients with inflammatory lung diseases. Several studies, including our own, have demonstrated compelling benefits from the administration of MSCs in animal models of lung injury. These studies are leading to growing interest in the therapeutic use of MSCs in inflammatory lung diseases. In this Review, we describe how the immunoregulatory effects of MSCs can confer substantial protection in the setting of lung diseases such as acute lung injury, chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. We also address potential pitfalls related to the therapeutic use of MSCs in fibrotic lung diseases such as idiopathic pulmonary fibrosis. In addition, we identify emerging areas for MSC- based therapies in modulating oxidative stress and in attenuating inflammation in alcohol-related acute lung injury. PMID:19352305

  14. Chronic inflammatory systemic diseases

    OpenAIRE

    Straub, Rainer H.; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history sta...

  15. Membranous nephropathy and lupus-like syndrome after hematopoietic cell transplantation: a case report

    OpenAIRE

    Stylianou Kostas; Stratakis Stavros; Mavroeidi Vasiliki; Petrakis Ioannis; Xydakis Dimitris; Vardaki Eleftheria; Stratigis Spyros; Perakis Kostas; Katsarou Theodora; Kanellou Peggy; Xylouri Irene; Petraki Constantina; Alexandrakis Michael; Daphnis Eugene

    2010-01-01

    Abstract Introduction The kidney is increasingly recognised as a target organ of chronic graft-versus-host disease after hematopoietic cell transplantation in the context of the development of the nephrotic syndrome. Chronic graft-versus-host disease is associated with autoimmune phenomena similar, but not identical, to those observed in various rheumatologic disorders, implicating autoimmunity as an important component of the disease. Case presentation We report the case of a 57-year-old Cau...

  16. Chronic obstructive pulmonary disease.

    Science.gov (United States)

    Barnes, Peter J; Burney, Peter G J; Silverman, Edwin K; Celli, Bartolome R; Vestbo, Jørgen; Wedzicha, Jadwiga A; Wouters, Emiel F M

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression. PMID:27189863

  17. Chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    V K Vijayan

    2013-01-01

    Full Text Available The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are observed in central airways, small airways and alveolar space. The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair. Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec to FVC (forced vital capacity ratio <0.70. COPD is characterized by an accelerated decline in FEV1. Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure, hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity, bone disease (osteoporosis and osteopenia, stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline. The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death and this is essential to guide therapy. COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor. Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support. Lung volume reduction surgery and lung transplantation are advised in selected severe patients. Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease

  18. Are there effective new strategies for the treatment of acute and chronic GvHD?

    OpenAIRE

    Chao, Nelson J.

    2008-01-01

    The molecular biology and pathophysiology underlying graft-versus-host disease (GvHD) remains an area of intensive research. Understanding normal and abnormal developments of both the innate and adaptive immune systems are beginning to provide understanding of the details of relevant pathways. Recent work in gene-expression profiling suggests a critical next step in identifying broader patterns that will stand up to examination in independent data sets and provide a sturdy basis for targeted ...

  19. Bone marrow transplantation: graft versus host disease and oral changes = Transplante de medula óssea: doença enxerto versus hospedeiro e alterações orais

    Directory of Open Access Journals (Sweden)

    Lima, Emeline das Neves de Araújo

    2012-01-01

    Conclusão: Diante da prevalência de alterações orais relativamente alta associada à DEVH em pacientes submetidos ao TMO, o presente estudo confirma a necessidade de se considerar a odontologia no exame, diagnóstico, tratamento e prognóstico de possíveis complicações após o transplante de medula óssea

  20. Graft-versus-host disease and membranous nephropathy in post-allogeneic haematopoietic stem cell transplantation%移植物抗宿主反应与造血干细胞移植术后膜性肾病

    Institute of Scientific and Technical Information of China (English)

    黄湘华; 秦卫松; 张明超; 郑春霞; 曾彩虹; 刘志红

    2010-01-01

    目的:分析异基因造血干细胞移植术后膜性肾病(MN)的临床病理特征,并探讨其与慢性移植物抗宿主反应(GVHD)之间的关系. 方法:选取在我科经活检证实的5例异基因造血干细胞移植(Allo-HSCT)术后MN为研究对象,分析5例患者的临床表现,实验室结果以及肾脏病理形态学、免疫荧光及电镜的病理特点,并行IgG亚型免疫荧光染色,观察不同IgG亚型在肾小球分布的特点及与nephrin分布的关系.此外,利用Western印迹的方法,我们检测了患者血清中是否存在抗M型磷脂酶A2受体(PLA2R)自身抗体. 结果:5例患者的临床病理特征如下:(1)移植前无肾脏病史及肾脏病家族史;(2)所有患者在出现蛋白尿的时候均合并存在慢性GVHD(cGVHD)的表现,R4例患者既往有急性GVHD(aGVHD)的病史,经过有效的抗GVHD治疗后,患者的蛋白尿也随之好转;(3)部分患者自身抗体检测阳性,肾组织伴有CA及Clq的沉积,提示体内存在自身免疫现象;(4)肾组织沉积的IgG以IgG4为主,其分布与nephri一致;(5)抗PLA2R自身抗体的检测结果显示5例患者中仅有1例阳性,阳性率远低于特发性膜性肾病(IMN)的检测结果. 结论:我们认为Allo-HSCT术后的MN也是cGVHD的一种表现形式,其发病机制可能与移植入的免疫细胞产生了抗宿主足细胞的抗体有关,且抗体的类型不同于IMN的抗PLA2R自身抗体.

  1. Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Su Mi; Choi, Ihl Bohng; Kang, Ki Mun; Kim, In Ah; Shinn, Kyung Sub; Kim, Choon Choo; Kim, Dong Jip [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1994-06-15

    Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6 fractions/3 days (6 patients) or 1320 cGy/8 fractions/4 days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase.

  2. Immune development and regulation in young children - Potential markers for prediction of health and disease.

    OpenAIRE

    Reubsaet, L.L.

    2014-01-01

    The human immune system is complex and is formed and shaped during life by many triggers. Different subsets of T helper cells are involved in immunity against pathogens, but can also play a role in inflammatory diseases like allergy, asthma and allo-reactive disease. The regulation of these inflammatory responses is mediated by the regulatory T cell (Treg). During our whole life these different T cell subsets try to maintain a balance within the immune system. Graft-versus-Host disease Alloge...

  3. Screening for Chronic Kidney Disease

    Science.gov (United States)

    Understanding Task Force Recommendations Screening for Chronic Kidney Disease The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation on Screening for Chronic Kidney Disease (CKD) . This recommendation ...

  4. Chronic granulomatous disease associated with chronic glomerulonephritis

    DEFF Research Database (Denmark)

    Frifelt, J J; Schønheyder, Henrik Carl; Valerius, Niels Henrik;

    1985-01-01

    A boy with chronic granulomatous disease (CGD) developed glomerulonephritis at the age of 12 years. The glomerulonephritis progressed to terminal uraemia at age 15 when maintenance haemodialysis was started. The clinical course was complicated by pulmonary aspergillosis and Pseudomonas septicaemia...

  5. Late and chronic Lyme disease.

    Science.gov (United States)

    Donta, Sam T

    2002-03-01

    This article reviews the late and chronic manifestations of Lyme disease. Special attention is given to the chronic manifestations of the disease, detailing its pathogenesis, clinical spectrum, and laboratory criteria for the diagnosis. Based on experimental evidence and experience, approaches to the successful treatment of the late and chronic disease are outlined. Much additional work is needed to improve the understanding of the underlying pathophysiology of the disease, its diagnosis and treatment.

  6. Chronic granulomatous disease

    Directory of Open Access Journals (Sweden)

    Nair Pradeep

    2005-01-01

    Full Text Available A 2½-year-old child presented with multiple discrete granulomatous lesions on the face and flexural regions since the age of 2 months along with lymphadenopathy. The patient also had recurrent bouts of pyodermas and respiratory tract infections. Biopsy of the lesion showed necrosis of tissue with suppuration and histiocytes but no evidence of tuberculosis, fungal infections or atypical mycobacteria. Lymph node biopsy also showed necrosis with suppuration but no infective organism. Nitroblue tetrazolium test was negative indicating that the neutrophils failed to oxidize the dye. We are reporting here a rare case of chronic granulomatous disease.

  7. Chronic granulomatous disease.

    Science.gov (United States)

    Nair, Pradeep S; Moorthy, Prasanna K; Suprakasan, S; Jayapalan, Sabeena; Preethi, K

    2005-01-01

    A 2(1/2)-year-old child presented with multiple discrete granulomatous lesions on the face and flexural regions since the age of 2 months along with lymphadenopathy. The patient also had recurrent bouts of pyodermas and respiratory tract infections. Biopsy of the lesion showed necrosis of tissue with suppuration and histiocytes but no evidence of tuberculosis, fungal infections or atypical mycobacteria. Lymph node biopsy also showed necrosis with suppuration but no infective organism. Nitroblue tetrazolium test was negative indicating that the neutrophils failed to oxidize the dye. We are reporting here a rare case of chronic granulomatous disease. PMID:16394414

  8. Hyperphosphatemia of Chronic Kidney Disease

    OpenAIRE

    Hruska, Keith A.; Mathew, Suresh; Lund, Richard; Qiu, Ping; Pratt, Raymond

    2008-01-01

    Observational studies have determined hyperphosphatemia to be a cardiovascular risk factor in chronic kidney disease. Mechanistic studies have elucidated that hyperphosphatemia is a direct stimulus to vascular calcification, which is one cause of morbid cardiovascular events contributing to the excess mortality of chronic kidney disease. This review describes the pathobiology of hyperphosphatemia that develops as a consequence of positive phosphate balance in chronic kidney disease and the me...

  9. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Patrizia Chiusolo

    2010-05-01

    Full Text Available

    Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment.

    Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%:

    A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity.

    The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients.

    Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

     

  10. Understanding anemia of chronic disease.

    Science.gov (United States)

    Fraenkel, Paula G

    2015-01-01

    The anemia of chronic disease is an old disease concept, but contemporary research in the role of proinflammatory cytokines and iron biology has shed new light on the pathophysiology of the condition. Recent epidemiologic studies have connected the anemia of chronic disease with critical illness, obesity, aging, and kidney failure, as well as with the well-established associations of cancer, chronic infection, and autoimmune disease. Functional iron deficiency, mediated principally by the interaction of interleukin-6, the iron regulatory hormone hepcidin, and the iron exporter ferroportin, is a major contributor to the anemia of chronic disease. Although anemia is associated with adverse outcomes, experimental models suggest that iron sequestration is desirable in the setting of severe infection. Experimental therapeutic approaches targeting interleukin-6 or the ferroportin-hepcidin axis have shown efficacy in reversing anemia in either animal models or human patients, although these agents have not yet been approved for the treatment of the anemia of chronic disease.

  11. Chronic active Epstein-Barr virus infection with marked pericardial effusion successfully treated with allogeneic peripheral blood stem cell transplantation.

    Science.gov (United States)

    Matsui, Shinichiro; Takeda, Yusuke; Isshiki, Yusuke; Yamazaki, Atsuko; Nakao, Sanshiro; Takaishi, Koji; Nagao, Yuhei; Hasegawa, Nagisa; Togasaki, Emi; Shimizu, Ryoh; Kawajiri, Chika; Sakai, Shio; Mimura, Naoya; Takeuchi, Masahiro; Ohwada, Chikako; Sakaida, Emiko; Iseki, Tohru; Imadome, Ken-Ichi; Nakaseko, Chiaki

    2016-05-01

    A 23-year-old woman presented with a persistent fever and shortness of breath. Computed tomography showed marked pericardial effusion, hepatosplenomegaly, and cervical and mediastinal lymph node swelling. Epstein-Barr virus (EBV) antibody titers were abnormally elevated, and the copy number of EBV-DNA was increased in peripheral blood. Based on these observations, she was diagnosed with chronic active EBV infection (CAEBV). The EBV-infected cells in her peripheral blood were CD4(+)T lymphocytes. Fever and pericardial effusion improved following treatment with a combination of prednisolone, etoposide, and cyclosporine; however, peripheral blood EBV-DNA levels remained high. The patient underwent allogeneic peripheral blood stem cell transplantation from an EBV-seronegative, HLA-matched sibling donor, with fludarabine and melphalan conditioning. The post-transplantation course was uneventful, except for mild skin acute graft-versus-host disease (grade 2). EBV-DNA became undetectable in peripheral blood 98 days post transplantation. She has since been in good health without disease recurrence. CAEBV is a potentially fatal disease caused by persistent EBV infection of T lymphocytes or natural killer cells, thus requiring prompt treatment and allogeneic transplantation. Pericardial effusion is rarely observed in CAEBV and can impede its diagnosis. Therefore, we should be aware that patients may present with marked pericardial effusion as an initial manifestation of CAEBV. PMID:27263789

  12. Chronic Kidney Disease and Medicines

    Science.gov (United States)

    ... from our online catalog. Alternate Language URL Español Chronic Kidney Disease and Medicines: What You Need to Know Page ... What you need to know Because you have chronic kidney disease, you should take steps to protect your kidneys. ...

  13. Clinical Scenarios in Chronic Kidney Disease: Chronic Tubulointerstitial Diseases.

    Science.gov (United States)

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Chronic tubulointerstitial diseases are a common final pathway toward chronic renal failure regardless the primary damage (glomerular, vascular or directly the tubulointerstitium). Chronic tubulointerstitial nephritis (CTN) is characterized by interstitial scarring, fibrosis and tubule atrophy, resulting in progressive chronic kidney disease. Most frequent causes of CTN are drugs, heavy metals, obstructive uropathy, nephrolithiasis, reflux disease, immunologic diseases, neoplasia, ischemia, metabolic diseases, genetics and miscellaneous. At ultrasound (US), kidneys' morphological aspect is similar in all forms of chronic interstitial nephropathy and only chronic pyelonephritis with or without reflux shows distinguishing characteristics. In interstitial nephropathy, kidneys' profiles are finely irregular and corticomedullary differentiation is altered because of a diffused hyperechogenicity. The only indirect sign of chronic interstitial damage can be derived from the value of intrarenal resistive indexes that hardly overcome 0.75. US is mandatory in clinical chronic pyelonephritis work-up because it provides information on kidney's diameter and on growth nomogram in children. Renal profiles can be more or less altered depending on the number of cortical scars and the presence of pseudonodular areas of segmental compensatory hypertrophy. In the early stages, US diagnosis of renal tuberculosis is difficult because parenchymal lesions are non-specific. US sensitivity in the diagnosis of hydronephrosis is very high, close to 100% and, finally, US is the first choice imaging technique in the diagnosis of urinary lithiasis. PMID:27169608

  14. Chronic diseases and mental disorder.

    NARCIS (Netherlands)

    Verhaak, P.F.M.; Heijmans, M.J.W.M.; Peters, L.; Rijken, M.

    2005-01-01

    The aim of this study was to achieve a better understanding of the relationship between chronic medical illness and mental distress. Therefore, the association between chronic medical illness and mental distress was analysed, taking into account the modifying effects of generic disease characteristi

  15. Chronic diseases in elderly men

    DEFF Research Database (Denmark)

    Nielsen, Morten Frost Munk; Wraae, Kristian; Gudex, Claire;

    2012-01-01

    OBJECTIVE: prevalence estimates for chronic diseases and associated risk factors are needed for priority setting and disease prevention strategies. The aim of this cross-sectional study was to estimate the self-reported and clinical prevalence of common chronic disorders in elderly men. STUDY......-reported data on risk factors and disease prevalence were compared with data from hospital medical records. RESULTS: physical inactivity, smoking and excessive alcohol intake were reported by 27, 22 and 17% of the study population, respectively. Except for diabetes, all the chronic diseases investigated......, including hypertension, musculoskeletal and respiratory diseases were underreported by study participants. Erectile dysfunction and hypogonadism were substantially underreported in the study population even though these diseases were found to affect 48 and 21% of the participants, respectively. CONCLUSIONS...

  16. Occupational chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Omland, Oyvind; Würtz, Else Toft; Aasen, Tor Brøvig;

    2014-01-01

    Occupational-attributable chronic obstructive pulmonary disease (COPD) presents a substantial health challenge. Focusing on spirometric criteria for airflow obstruction, this review of occupational COPD includes both population-wide and industry-specific exposures.......Occupational-attributable chronic obstructive pulmonary disease (COPD) presents a substantial health challenge. Focusing on spirometric criteria for airflow obstruction, this review of occupational COPD includes both population-wide and industry-specific exposures....

  17. Nutrition in Chronic Liver Disease

    OpenAIRE

    Marco Silva; Sara Gomes; Armando Peixoto; Paulo Torres-Ramalho; Hélder Cardoso; Rosa Azevedo; Carla Cunha; Guilherme Macedo

    2015-01-01

    Protein-calorie malnutrition is a transversal condition to all stages of chronic liver disease. Early recognition of micro or macronutrient deficiencies is essential, because the use of nutritional supplements reduces the risk of complications. The diet of patients with chronic liver disease is based on a standard diet with supplements addition as necessary. Restrictions may be harmful and should be individualized. Treatment management should aim to maintain an adequate protein and caloric...

  18. Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD.

    Science.gov (United States)

    Leveque-El Mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A; Cheong, Melody; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Alexander, Kylie A; Clouston, Andrew D; Blazar, Bruce R; Hill, Geoffrey R; MacDonald, Kelli P A

    2016-08-11

    Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD. PMID:27338097

  19. Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD.

    Science.gov (United States)

    Leveque-El Mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A; Cheong, Melody; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Alexander, Kylie A; Clouston, Andrew D; Blazar, Bruce R; Hill, Geoffrey R; MacDonald, Kelli P A

    2016-08-11

    Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD.

  20. Research progress of CD4+CD25+ regulatory T cell in bone marrow hematopoietic system diseases%CD4+CD25+调节性T细胞在骨髓造血系统疾病中的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘增慧; 李勇华

    2011-01-01

    CD4 + CD25 + regulatory T cell is a unique T-cell subsets with immune regulation function. Natural CD4+CD25 + regulatory T cell originates from the thymus and acquired CD4+CD25 + regulatory T cell can be induced from CD4* CD25 - T cells in peripheral blood. A specific transcription inhibicory factor-foxp3 , can be expressed in its molecule surface, besides, it also can express other membrane molecules, such as CD4, CD25, CTLA-4 ( CD152), GITR, CD103, CD62L, CD69, CD134, CD71, CD54, CD45RA , TGF-β1 , IL-10, glactin-1 , neuropilin-1 , etc. Its main function is immunosuppression and immune anergy. Recent research finds that it overexpresses in acute myeloid leukemia, chronic lymphocytic leukemia and high-risk myelodysplastic syndrome. However, in aplastic anemia its expression is much lower than normal. Other researchers believe that it has much to do with acute graft versus host disease, in its occurrence and development. In this article, we will review the recent research results of CD4 + CD25 + regulatory T cell in bone marrow hematopoietic system diseases, specifically, in leukemia, acute graft versus host disease, aplastic anemia, myelodysplastic syndrome and multiple myeloma.%CD4+CD25+调节性T细胞(regulatory T cell, Treg)是具有独特免疫调节功能的T细胞亚群. 天然CD4+CD25+ Treg起源于胸腺,外周血中CD4+CD25-T细胞亦可诱导产生.其分子表面表达特异性的转录抑制因子Foxp3,还表达CD4、CD25、CTLA-4(CD152))、GITR、CD103、CD62L、CD69、CD134、CD71、CD54、CD45RA、TGF-β1、IL-10、半乳糖结合蛋白(glactin)-1、神经菌毛素(neuropilin)-1等膜分子,具有免疫抑制和免疫无能作用.近年来研究发现,急性髓细胞白血病(acute myeloid leukemia,AML)、慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)、高危骨髓异常增生综合征(myelodysplastic syndrome, MDS)患者Treg表达异常增高,而在再生障碍性贫血(aplastic anemia,AA)患者表达明显降低,其异常表达

  1. Children, Sports, and Chronic Disease.

    Science.gov (United States)

    Goldberg, Barry

    1990-01-01

    Discusses four chronic diseases (cystic fibrosis, congenital heart disease, rheumatoid arthritis, and asthma) that affect American children. Many have their physical activities unnecessarily restricted, though sports and exercise can actually alleviate symptoms and improve their psychosocial development. Physicians are encouraged to prescribe…

  2. A summary about dendritic cells in skin diseases

    Institute of Scientific and Technical Information of China (English)

    Jianguo Huang; Robert Gniadecki

    2005-01-01

    Dendritic cellls (DCs) comprise an essential component of the immune system, are crucial in the initiation of antigen specific immune responses. In this summary we focus on summarizing on the central role of DCs in skin diseases: Bullous dermatoses,Dermatitis, Psoriasis, Lichen Planus , Graft-versus-host disease, Connect Tissue Diseases, Virus Diseases, Fungi Diseases, HIV, Urticaria, Urticaria pigmentosa, Mastocytosis, Tumour, Solar dermatoses. Moreover, in this summary we review the distribution and phenotype of DCs in human skin. Markers and phenotyps ' s study have provided strong support for a concept in which DCs play an important role in the pothogenesis of some skin diseases.

  3. Skin biopsy: Biopsy issues in specific diseases.

    Science.gov (United States)

    Elston, Dirk M; Stratman, Erik J; Miller, Stanley J

    2016-01-01

    Misdiagnosis may result from biopsy site selection, technique, or choice of transport media. Important potential sources of error include false-negative direct immunofluorescence results based on poor site selection, uninformative biopsy specimens based on both site selection and technique, and spurious interpretations of pigmented lesions and nonmelanoma skin cancer based on biopsy technique. Part I of this 2-part continuing medical education article addresses common pitfalls involving site selection and biopsy technique in the diagnosis of bullous diseases, vasculitis, panniculitis, connective tissue diseases, drug eruptions, graft-versus-host disease, staphylococcal scalded skin syndrome, hair disorders, and neoplastic disorders. Understanding these potential pitfalls can result in improved diagnostic yield and patient outcomes.

  4. Chronic diseases and mental disorder.

    OpenAIRE

    Verhaak, P.F.M.; Heijmans, M.J.W.M.; L. Peters; Rijken, M.

    2005-01-01

    The aim of this study was to achieve a better understanding of the relationship between chronic medical illness and mental distress. Therefore, the association between chronic medical illness and mental distress was analysed, taking into account the modifying effects of generic disease characteristics (concerning course, control and possible stressful consequences), physical quality of life indicators and social and relationship problems. Panel data from the Dutch national Panel of Patients w...

  5. Interferon α: the salvage therapy for patients with unsatisfactory response to minimal residual disease-directed modified donor lymphocyte infusion

    Institute of Scientific and Technical Information of China (English)

    Mo Xiaodong; Zhao Xiangyu; Xu Lanping; Liu Daihong; Zhang Xiaohui; Chen Huan; Wang Yu

    2014-01-01

    Background Minimal residual disease (MRD)-directedmodified donor lymphocyte infusion (mDLI) is used to treat relapse after hematopoietic stem cell transplantation (HSCT).For patients who experience an unsatisfactory response tomDLI,relapse is usually inevitable.Therefore,we sought to evaluate the efficacy ofinterferon α therapy in these patients.Methods Regular MRD monitoring was carried out after the HSCT.The patients who were MRD-positive underwent mDLI.Patients with an unsatisfactory response to mDLI received interferon α therapy (3 million units,twice weekly) with regular monitoring of MRD.To ensure the immunomodulatory effects of interferon α,immunosuppressant treatment would be stopped before interferon α treatment.Results Five patients with an unsatisfactory response to mDLI treatment received interferon α (3 had t(8;21) chromosomal translocation acute myeloid leukemia,and 2 had common acute leukemia).They had significantly reduced or resolved MRD.Four patients developed chronic graft-versus-host disease.Two of the 5 patients reported transient fevers,and no significant bone marrow suppression was observed.All of them were in continuous complete remission after interferon α treatment.The median survival time was 469 days (range 368-948 days).Conclusions In patients with an unsatisfactory response to MRD-directed mDLI,interferon α may directly or indirectly induce the graft-versus-leukemia effect to improve mDLI efficacy and clear MRD.

  6. Chronic Venous Disease under pressure

    NARCIS (Netherlands)

    S.W.I. Reeder (Suzan)

    2013-01-01

    textabstractIn chapter 1 we provide a general introduction of this thesis. Chronic venous disease (CVD) is a common medical condition that affects 2-64% of the worldwide population and leads to leg ulcers in 1% of the Western population. Venous leg ulceration (VLU) has an unfavorable prognosis with

  7. Metformin in chronic kidney disease

    DEFF Research Database (Denmark)

    Heaf, James

    2014-01-01

    Metformin has traditionally been regarded as contraindicated in chronic kidney disease (CKD), though guidelines in recent years have been relaxed to permit therapy if the glomerular filtration rate (GFR) is > 30 mL/min. The main problem is the perceived risk of lactic acidosis (LA). Epidemiological...

  8. Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia

    International Nuclear Information System (INIS)

    A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incident at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy. (Author)

  9. The impact of pre-transplant minimal residual disease on outcome of intensified myeloablative cord blood transplant for acute myeloid leukemia in first or second complete remission.

    Science.gov (United States)

    Zheng, Changcheng; Zhu, Xiaoyu; Tang, Baolin; Zhang, Lei; Geng, Liangquan; Liu, Huilan; Sun, Zimin

    2016-01-01

    The impact of pretransplant minimal residual disease (MRD) on outcome of myeloablative cord blood transplant (CBT) for acute myeloid leukemia (AML) in complete remission (CR) has not been reported. Seventy-two AML patients were assessed for MRD before CBT, and the majority (84.7%) of these patients received single-unit CBT. All patients received intensified myeloablative conditioning with BUCY2 or TBICY plus high-dose cytarabine, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The cumulative incidences of neutrophil and platelet engraftment, acute or chronic GVHD were comparable between MRD-negative and MRD-positive groups. The cumulative incidence of transplant-related mortality (TRM) and relapse did not differ significantly between the two cohorts (25.6% vs. 32.5%, 16.1% vs. 19.2%; p = 0.52, 0.61). There were no apparent differences in 3-year overall survival (OS) (68.9% in MRD-negative group and 57.9% in MRD-positive group, p = 0.31) and 3-year leukemia-free survival (LFS) (62.5% in MRD-negative group and 52.7% in MRD-positive group, p = 0.42) between both groups. The current study suggests that AML patients in morphological CR1 or CR2 who have detectable MRD might benefit from unrelated CBT with intensified myeloablative conditioning. PMID:26690538

  10. Clinical Potential of Regulatory T Cell Therapy in Liver Diseases: An Overview and Current Perspectives

    Science.gov (United States)

    Jeffery, Hannah C.; Braitch, Manjit Kaur; Brown, Solomon; Oo, Ye Htun

    2016-01-01

    The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg). The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis, or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients. Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment, and good manufacturing practice facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases (AILD), chronic rejection, and posttransplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases, and solid organ transplantations. There have not been any new therapies for the AILD for more than three decades; thus, the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior, and microenvironment of Treg before applying the cells to the patients. PMID:27656181

  11. Clinical Potential of Regulatory T Cell Therapy in Liver Diseases: An Overview and Current Perspectives.

    Science.gov (United States)

    Jeffery, Hannah C; Braitch, Manjit Kaur; Brown, Solomon; Oo, Ye Htun

    2016-01-01

    The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg). The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis, or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients. Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment, and good manufacturing practice facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases (AILD), chronic rejection, and posttransplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases, and solid organ transplantations. There have not been any new therapies for the AILD for more than three decades; thus, the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior, and microenvironment of Treg before applying the cells to the patients. PMID:27656181

  12. Chronic Lyme disease: a review.

    Science.gov (United States)

    Marques, Adriana

    2008-06-01

    Studies have shown that most patients diagnosed with chronic Lyme disease either have no objective evidence of previous or current infection with Borrelia burgdorferi or are patients who should be classified as having post-Lyme disease syndrome, which is defined as continuing or relapsing nonspecific symptoms (such as fatigue, musculoskeletal pain, and cognitive complaints) in a patient previously treated for Lyme disease. Despite extensive study, there is currently no clear evidence that post-Lyme disease syndrome is caused by persistent infection with B burgdorferi. Four randomized placebo-controlled studies have shown that antibiotic therapy offers no sustained benefit to patients who have post-Lyme disease syndrome. These studies also showed a substantial placebo effect and a significant risk of treatment-related adverse events. Further research to elucidate the mechanisms underlying persistent symptoms after Lyme disease and controlled trials of new approaches to the treatment and management of these patients are needed.

  13. Perspectives on "chronic Lyme disease".

    Science.gov (United States)

    Baker, Phillip J

    2008-07-01

    There is much controversy about the treatment of Lyme disease with respect to 2 poorly defined entities: "chronic Lyme disease" and "posttreatment Lyme disease syndrome." In the absence of direct evidence that these conditions are the result of a persistent infection, some mistakenly advocate extended antibiotic therapy (>/=6 months), which can do great harm and has resulted in at least 1 death. The purpose of this brief report is to review what is known from clinical research about these conditions to assist both practicing physicians and lawmakers in making sound and safe decisions with respect to treatment.

  14. Risk Factors for Chronic Kidney Disease

    Science.gov (United States)

    ... Materials Webinars Tips & Stories Links & Resources Learn About Chronic Kidney Disease Kidney Glossary Ask Our Expert Toll-Free Helpline: ... Questions What You Can Do Download all the chronic kidney disease information presented here. Preview Our CKD Booklets Stage ...

  15. Pericytes in chronic lung disease.

    Science.gov (United States)

    Rowley, Jessica E; Johnson, Jill R

    2014-01-01

    Pericytes are mesenchymal cells embedded within the abluminal surface of the endothelium of microvessels such as capillaries, pre-capillary arterioles, post-capillary and collecting venules, where they maintain microvascular homeostasis and participate in angiogenesis. In addition to their roles in supporting the vasculature and facilitating leukocyte extravasation, pericytes have been recently investigated as a subpopulation of mesenchymal stem cells (MSCs) due to their capacity to differentiate into numerous cell types including the classic MSC triad, i.e. osteocytes, chondrocytes and adipocytes. Other studies in models of fibrotic inflammatory disease of the lung have demonstrated a vital role of pericytes in myofibroblast activation, collagen deposition and microvascular remodelling, which are hallmark features of chronic lung diseases such as asthma, chronic obstructive pulmonary disorder, pulmonary fibrosis and pulmonary hypertension. Further studies into the mechanisms of the pericyte-to-myofibroblast transition and migration to fibrotic foci will hopefully clarify the role of these cells in chronic lung disease and confirm the importance of pericytes in human fibrotic pulmonary disease. PMID:25034005

  16. Treatment of immune thrombocytopenia after allogeneic cord blood stem cell transplantation with rituximab: a case report

    Institute of Scientific and Technical Information of China (English)

    Mengxing Li; Jishi Wang; Yan Zhang; Zhiqiang Sun; Yanju Li; Xiaoli Zhou

    2013-01-01

    Immune thrombocytopenia (ITP) is a chronic disease resulting from increased platelet destruction and impaired platelet production. Secondary ITP can be a manifestation of chronic graft-versus-host disease (GVHD) and represent a lymphoproliferative disorder. A boy with chronic graft-versus-host disease after cord blood stem cell transplantation who had severe refractory immune-mediated thrombocytopenia received infusion of rituximab weekly, 375 mg/m2, for 4 weeks. Platelets count of the patient was recovered, and rituximab was well tolerated with no severe toxicity observed during treatment.

  17. Vouchers for chronic disease care.

    Science.gov (United States)

    Watts, Jennifer J; Segal, Leonie

    2008-08-01

    This paper explores the economic implications of vouchers for chronic disease management with respect to achieving objectives of equity and efficiency. Vouchers as a payment policy instrument for health care services have a set of properties that suggest they may address both demand-side and supply-side issues, and contribute to equity and efficiency. They provide a means whereby health care services can be targeted at selected groups, enabling consumer choice of provider, and encouraging competition in the supply of health services. This analysis suggests that, when structured appropriately, vouchers can support consumers to choose services that will meet their health care needs and encourage competition among providers. Although they may not be appropriate across the entire health care system, there are features of vouchers that make them a potentially attractive option, especially for the management of chronic disease.

  18. Endothelins in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl

    1996-01-01

    This review describes recent progress in the accumulation of knowledge about the endothelins (ETs), a family of vasoactive 21-amino acid polypeptides, in chronic liver disease. Particular prominence is given to the dynamics of ET-1 and ET-3 and their possible relation to the disturbed circulation...... renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal venous hypertension....... In addition, marked associations with disturbance of systemic haemodynamics and with abnormal distribution of blood volume have been reported. Although the pathophysiological importance of the ET system in chronic liver disease is not completely understood, similarities to other vasopressive...

  19. Chronic Obstructive Pulmonary Disease Biomarkers

    Directory of Open Access Journals (Sweden)

    Tatsiana Beiko

    2016-04-01

    Full Text Available Despite significant decreases in morbidity and mortality of cardiovascular diseases (CVD and cancers, morbidity and cost associated with chronic obstructive pulmonary disease (COPD continue to be increasing. Failure to improve disease outcomes has been related to the paucity of interventions improving survival. Insidious onset and slow progression halter research successes in developing disease-modifying therapies. In part, the difficulty in finding new therapies is because of the extreme heterogeneity within recognized COPD phenotypes. Novel biomarkers are necessary to help understand the natural history and pathogenesis of the different COPD subtypes. A more accurate phenotyping and the ability to assess the therapeutic response to new interventions and pharmaceutical agents may improve the statistical power of longitudinal clinical studies. In this study, we will review known candidate biomarkers for COPD, proposed pathways of pathogenesis, and future directions in the field.

  20. Placental Origins of Chronic Disease.

    Science.gov (United States)

    Burton, Graham J; Fowden, Abigail L; Thornburg, Kent L

    2016-10-01

    Epidemiological evidence links an individual's susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically this should not be unexpected, for organ systems are at their most plastic when progenitor cells are proliferating and differentiating. Influences operating at this time can permanently affect their structure and functional capacity, and the activity of enzyme systems and endocrine axes. It is now appreciated that such effects lay the foundations for a diverse array of diseases that become manifest many years later, often in response to secondary environmental stressors. Fetal development is underpinned by the placenta, the organ that forms the interface between the fetus and its mother. All nutrients and oxygen reaching the fetus must pass through this organ. The placenta also has major endocrine functions, orchestrating maternal adaptations to pregnancy and mobilizing resources for fetal use. In addition, it acts as a selective barrier, creating a protective milieu by minimizing exposure of the fetus to maternal hormones, such as glucocorticoids, xenobiotics, pathogens, and parasites. The placenta shows a remarkable capacity to adapt to adverse environmental cues and lessen their impact on the fetus. However, if placental function is impaired, or its capacity to adapt is exceeded, then fetal development may be compromised. Here, we explore the complex relationships between the placental phenotype and developmental programming of chronic disease in the offspring. Ensuring optimal placentation offers a new approach to the prevention of disorders such as cardiovascular disease, diabetes, and obesity, which are reaching epidemic proportions. PMID:27604528

  1. Ghrelin in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Wai W. Cheung

    2010-01-01

    Full Text Available Patients with chronic kidney disease (CKD often exhibit symptoms of anorexia and cachexia, which are associated with decreased quality of life and increased mortality. Chronic inflammation may be an important mechanism for the development of anorexia, cachexia, renal osteodystrophy, and increased cardiovascular risk in CKD. Ghrelin is a gastric hormone. The biological effects of ghrelin are mediated through the growth hormone secretagogue receptor (GHSR. The salutary effects of ghrelin on food intake and meal appreciation suggest that ghrelin could be an effective treatment for anorexic CKD patients. In addition to its appetite-stimulating effects, ghrelin has been shown to possess anti-inflammatory properties. The known metabolic effects of ghrelin and the potential implications in CKD will be discussed in this review. The strength, shortcomings, and unanswered questions related to ghrelin treatment in CKD will be addressed.

  2. The differential diagnosis of inflammatory joint disease in maternal-fetal microchimerism

    Directory of Open Access Journals (Sweden)

    Seme Youssef Reda

    2013-12-01

    Full Text Available This study aimed at making the differential diagnosis of joint disease in a case of genetic chimerism in a female multiparous donor from the Regional Blood Bank of Guarapuava-PR (Hemocentro Regional de Guarapuava-PR, who had had three pregnancies of male fetuses. The patient showed joint pain prior to the last donation. It was possible to identify fetal cells remaining in circulation 20 years after her last pregnancy. Laboratory tests for acute phase proteins revealed possible termination of immune tolerance to circulating fetal cells. Thus, a hypothesis of graft-versus-host disease was formulated to explain the joint disease manifested by the donor.

  3. Neuropsychological functioning in chronic Lyme disease.

    Science.gov (United States)

    Westervelt, Holly James; McCaffrey, Robert J

    2002-09-01

    Lyme disease is currently the most common vector-borne illness in the United States. The disease is multisystemic, and chronic disease, in particular, may be associated with neuropsychological deficits. However, to date, only a few empirical studies exist, which examine the neuropsychological sequelae associated with chronic Lyme disease. A review of the literature shows that the deficits observed in adults with chronic Lyme disease are generally consistent with the deficits that can be seen in processes with primarily frontal systems involvement. These observations are generally consistent with neuroradiologic findings. The clinical presentation in chronic Lyme disease and the nature of the neuropsychological deficits are discussed, as are several central issues in understanding neuropsychological functioning in chronic Lyme disease, such as the impact of chronic illness, response to treatment, and the relationship between neuropsychological performance and depression, fatigue, and neurological indicators of disease.

  4. Chronic Disease and Childhood Development: Kidney Disease and Transplantation.

    Science.gov (United States)

    Klein, Susan D.; Simmons, Roberta G.

    As part of a larger study of transplantation and chronic disease and the family, 124 children (10-18 years old) who were chronically ill with kidney disease (n=72) or were a year or more post-transplant (n=52) were included in a study focusing on the effects of chronic kidney disease and transplantation on children's psychosocial development. Ss…

  5. HIV and chronic kidney disease.

    Science.gov (United States)

    Naicker, Saraladevi; Rahmanian, Sadaf; Kopp, Jeffrey B

    2015-01-01

    Chronic kidney disease (CKD) is a frequent complication of HIV infection, occurring in 3.5 - 48.5%, and occurs as a complication of HIV infection, other co-morbid disease and infections and as a consequence of therapy of HIV infection and its complications. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune complex disease is the second most common diagnosis obtained from biopsies of patients with HIV-CKD. CKD is mediated by factors related to the virus, host genetic predisposition and environmental factors. The host response to HIV infection may influence disease phenotype through activation of cytokine pathways. With the introduction of antiretroviral therapy (ART), there has been a decline in the incidence of HIVAN, with an increasing prevalence of focal segmental glomerulosclerosis. Several studies have demonstrated the overall improvement in kidney function when initiating ART for HIV CKD. Progression to end stage kidney disease has been reported to be more likely when high grade proteinuria, severely reduced eGFR, hepatitis B and/C co-infection, diabetes mellitus, extensive glomerulosclerosis, and chronic interstitial fibrosis are present. Improved renal survival is associated with use of renin angiotensin system blockers and viral suppression. Many antiretroviral medications are partially or completely eliminated by the kidney and require dose adjustment in CKD. Certain drug classes, such as the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, are metabolized by the liver and do not require dose adjustment. HIV-infected patients requiring either hemo- or peritoneal dialysis, who are stable on ART, are achieving survival rates comparable to those of dialysis patients without HIV infection. Kidney transplantation has been performed successfully in HIV

  6. Chronic kidney disease in children.

    Science.gov (United States)

    Becherucci, Francesca; Roperto, Rosa Maria; Materassi, Marco; Romagnani, Paola

    2016-08-01

    Chronic kidney disease (CKD) is a major health problem worldwide. Although relatively uncommon in children, it can be a devastating illness with many long-term consequences. CKD presents unique features in childhood and may be considered, at least in part, as a stand-alone nosologic entity. Moreover, some typical features of paediatric CKD, such as the disease aetiology or cardiovascular complications, will not only influence the child's health, but also have long-term impact on the life of the adult that they will become. In this review we will focus on the unique issues of paediatric CKD, in terms of aetiology, clinical features and treatment. In addition, we will discuss factors related to CKD that start during childhood and require appropriate treatments in order to optimize health outcomes and transition to nephrologist management in adult life. PMID:27478602

  7. Anemia of Chronic Liver Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hyun Chung; Lee, Jhung Sang; Koh, Chang Soon; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1971-09-15

    The pathogenetic mechanisms of anemia in patients with chronic liver disease were observed. Seventeen patients with moderate to advanced hepatic diseases were studied by various methods. Only patients without previous blood loss were included : 14 had cirrhosis, 2 had active chronic hepatitis, and one had inferior vena cava obstruction with associated liver cirrhosis. The followings were the results: 1. The anemia based on red blood cell count, Hb., and Ht. was found in 76.5-78.6% of the patients. 2. Red cell indices indicated that normo-macrocytic and normochromic anemia was present is the majority of the patients. 3. No evidence of megaloblastic anemia was found on the basis of the morphological examinations. 4. Serum iron, TIBC, % saturation and iron content in the bone marrow indicated that iron deficiency anemia was present in about half of the patients. 5. In the view of the erythrocyte dynamics, primary increase in the red cell destruction was ascribed to the cause of the anemia. 6. Decrease in the red cell survival time was not correlated with MCV, % saturation and S.L. ratio. Also, hemoglobin level was not correlated with MCV, % saturation and T{sub 50} Cr. Therefore, multiple causes may be involved in the pathogenesis of the anemia. 7. Anemia as determined by the red cell volume was found in only 60% of the patients. It may be possible that hemodilutional anemia is present.

  8. Chronic non-communicable diseases.

    Science.gov (United States)

    Unwin, N; Alberti, K G M M

    2006-01-01

    Chronic non-communicable diseases (NCD) account for almost 60% of global mortality, and 80% of deaths from NCD occur in low- and middle-income countries. One quarter of these deaths--almost 9 million in 2005--are in men and women aged globalisation of the food, tobacco and alcohol industries. Because NCD have a major impact on men and women of working age and their elderly dependents, they result in lost income, lost opportunities for investment, and overall lower levels of economic development. Reductions in the incidences of many NCD and their complications are, however, already possible. Up to 80% of all cases of cardiovascular disease or type-2 diabetes and 40% of all cases of cancer, for example, are probably preventable based on current knowledge. In addition, highly cost-effective measures exist for the prevention of some of the complications of established cardiovascular disease and diabetes. Achieving these gains will require a broad range of integrated, population-based interventions as well as measures focused on the individuals at high risk. At present, the international-assistance community provides scant resources for the control of NCD in poor countries, partly, at least, because NCD continue to be wrongly perceived as predominantly diseases of the better off. As urbanization continues apace and populations age, investment in the prevention and control of NCD in low-and middle-income countries can no longer be ignored. PMID:16899148

  9. Hypertrophic osteoarthropathy of chronic inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Oppenheimer, D.A.; Jones, H.H.

    1982-12-01

    The case of a 14-year old girl with painful periostitis and ulcerative colitis is reported. The association of chronic inflammatory bowel disease with osteoarthropathy is rare and has previously been reported in eight patients. The periosteal reaction found in association with inflammatory bowel disease is apparently related to a chronic disease course and may cause extreme localized pain.

  10. Right Ventricular Dysfunction in Chronic Lung Disease

    OpenAIRE

    Kolb, Todd M.; Hassoun, Paul M.

    2012-01-01

    Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, ex...

  11. Granulocyte Colony-stimulating Factor-primed Bone Marrow: An Excellent Stem-cell Source for Transplantation in Acute Myelocytic Leukemia and Chronic Myelocytic Leukemia

    Institute of Scientific and Technical Information of China (English)

    Yuhang Li; Min Jiang; Chen Xu; Jianlin Chen; Botao Li; Jun Wang; Jiangwei Hu

    2015-01-01

    Background:Steady-state bone marrow (SS-BM) and granulocyte colony-stimulating growth factor-primed BM/peripheral blood stem-cell (G-BM/G-PBSC) are the main stem-cell sources used in allogeneic hematopoietic stem-cell transplantation.Here,we evaluated the treatment effects of SS-BM and G-BM/G-PBSC in human leucocyte antigen (HLA)-identical sibling transplantation.Methods:A total of 226 patients (acute myelogenous leukemia-complete remission 1,chronic myelogenous leukemia-chronic phase 1) received SS-BM,G-BM,or G-PBSC from an HLA-identical sibling.Clinical outcomes (graft-versus-host disease [GVHD],overall survival,transplant-related mortality [TRM],and leukemia-free survival [LFS]) were analyzed.Results:When compared to SS-BM,G-BM gave faster recovery time to neutrophil or platelet (P < 0.05).Incidence of grade Ⅲ-Ⅳ acute GVHD and extensive chronic GVHD (cGVHD) was lower than seen with SS-BM (P < 0.05) and similar to G-PBSC.Although the incidence of cGVHD in the G-BM group was similar to SS-BM,both were lower than G-PBSC (P < 0.05).G-BM and G-PBSC exhibited similar survival,LFS,and TRM,but were significantly different from SS-BM (P < 0.05).There were no significant differences in leukemia relapse rates among the groups (P > 0.05).Conclusions:G-CSF-primed bone marrow shared the advantages of G-PBSC and SS-BM.We conclude that G-BM is an excellent stem-cell source that may be preferable to G-PBSC or SS-BM in patients receiving HLA-identical sibling hematopoietic stem-cell transplantation.

  12. Kidneys in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Marek Hartleb; Krzysztof Gutkowski

    2012-01-01

    Acute kidney injury (AKI),defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL,occurs in about 20% of patients hospitalized for decompensating liver cirrhosis.Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state,reduced effective blood volume and stimulation of vasoconstrictor hormones.The most common causes of AKI in cirrhosis are pre-renal azotemia,hepatorenal syndrome and acute tubular necrosis.Differential diagnosis is based on analysis of circumstances of AKI development,natriuresis,urine osmolality,response to withdrawal of diuretics and volume repletion,and rarely on renal biopsy.Chronic glomeruIonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients.AKI is one of the last events in the natural history of chronic liver disease,therefore,such patients should have an expedited referral for liver transplantation.Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension,and may be prematurely triggered by bacterial infections,nonbacterial systemic inflammatory reactions,excessive diuresis,gastrointestinal hemorrhage,diarrhea or nephrotoxic agents.Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy.The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion,which is effective in about 50% of patients.The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt,renal vasoprotection or systems of artificial liver support.

  13. Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema

    Science.gov (United States)

    ... Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema Recommend on Facebook Tweet Share Compartir Data are ... of adults who have ever been diagnosed with emphysema: 3.4 million Percent of adults who have ...

  14. Helicobacter Infection and Chronic Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Zhao-chun Chi; Xin-juan Yu; Quan-jiang Dong

    2014-01-01

    This paper reviews the recentHelicobacter infection associated with chronic liver disease. The bacteriology, prevalence, pathogenesis and diagnosis were reviewed. Future work should be conducted on the pathogenesis and treatment of this disease.

  15. Anemia of Inflammation and Chronic Disease

    Science.gov (United States)

    ... Disease Organizations (PDF, 270 KB). Alternate Language URL Anemia of Inflammation and Chronic Disease Page Content On ... Nutrition Points to Remember Clinical Trials What is anemia? Anemia is a condition in which a person ...

  16. Controversies in Chronic Kidney Disease Staging

    OpenAIRE

    Polkinghorne, Kevan R

    2011-01-01

    In 2002, a new chronic kidney disease staging system was developed by the US National Kidney Foundation. The classification system represented a new conceptual framework for the diagnosis of chronic kidney disease (moving to a schema based on disease severity defined by the glomerular filtration rate). While the introduction of the staging system stimulated significant clinical and research interest in kidney disease, there has been vigorous debate on its merits. This mini-review aims to summ...

  17. Is acute recurrent pancreatitis a chronic disease?

    OpenAIRE

    Mariani, Alberto; Testoni, Pier Alberto

    2008-01-01

    Whether acute recurrent pancreatitis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis. There is major evidence for considering alcoholic pancreatitis as a chronic disease ab initio while chronic pancreatitis lesions detectable in biliary acute recurrent pancreatitis (ARP) seem a casual association. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation, hereditary a...

  18. Chronic diseases among older cancer patients.

    NARCIS (Netherlands)

    Deckx, L.D.; Akker, M.A. van der; Metsemakers, J.M.; Knottnerus, A.K.; Schellevis, F.G.; Buntinx, F.B.

    2011-01-01

    Introduction: With the growing number of older cancer patients, the burden of chronic diseases among older cancer patients will become increasingly important. Chronic diseases often interfere with treatment decisions and prognosis for cancer patients. However, little is known about the occurrence of

  19. Osteoporosis in chronic obstructive pulmonary disease patients

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Schwarz, Peter

    2008-01-01

    The purpose of this review is to examine the state of knowledge and clinical practice in the association of chronic obstructive pulmonary disease to osteoporosis and fracture incidence.......The purpose of this review is to examine the state of knowledge and clinical practice in the association of chronic obstructive pulmonary disease to osteoporosis and fracture incidence....

  20. Gene Map of the HLA Region, Graves' Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Sasazuki, Takehiko; Inoko, Hidetoshi; Morishima, Satoko; Morishima, Yasuo

    2016-01-01

    The human leukocyte antigen (HLA) genomic region spanning about 4 Mb is the most gene dense and the polymorphic stretches in the human genome. A total of the 269 loci were identified, including 145 protein coding genes mostly important for immunity and 50 noncoding RNAs (ncRNAs). Biological function of these ncRNAs remains unknown, becoming hot spot in the studies of HLA-associated diseases. The genomic diversity analysis in the HLA region facilitated by next-generation sequencing will pave the way to molecular understanding of linkage disequilibrium structure, population diversity, histocompatibility in transplantation, and associations with autoimmune diseases. The 4-digit DNA genotyping of HLA for six HLA loci, HLA-A through DP, in the patients with Graves' disease (GD) and Hashimoto thyroiditis (HT) identified six susceptible and three resistant HLA alleles. Their epistatic interactions in controlling the development of these diseases are shown. Four susceptible and one resistant HLA alleles are shared by GD and HT. Two HLA alleles associated with GD or HT control the titers of autoantibodies to thyroid antigens. All these observations led us to propose a new model for the development of GD and HT. Hematopoietic stem cell transplantation from unrelated donor (UR-HSCT) provides a natural experiment to elucidate the role of allogenic HLA molecules in immune response. Large cohort studies using HLA allele and clinical outcome data have elucidated that (1) HLA locus, allele, and haplotype mismatches between donor and patient, (2) specific amino acid substitution at specific positions of HLA molecules, and (3) ethnic background are all responsible for the immunological events related to UR-HSCT including acute graft-versus-host disease (GVHD), chronic GVHD, graft-versus-leukemia (GvL) effect, and graft failure.

  1. Comparison of diagnostic tests in distinct well-defined conditions related to dry eye disease.

    Directory of Open Access Journals (Sweden)

    Monica Alves

    Full Text Available PURPOSE: This study compares signs, symptoms and predictive tools used to diagnose dry eye disease (DED and ocular surface disorders in six systemic well-defined and non-overlapping diseases. It is well known that these tests are problematic because of a lack of agreement between them in identifying these conditions. Accordingly, we provide here a comparative clinical profile analysis of these different diseases. METHODS: A spontaneous and continuous sample of patients with Sjögren's syndrome (SS (n=27, graft-versus-host-disease (GVHD (n=28, Graves orbitopathy (n=28, facial palsy (n=8, diabetes mellitus without proliferative retinopathy (n=14 and glaucoma who chronically received topical drugs preserved with benzalkonium chloride (n=20 were enrolled. Evaluation consisted of a comprehensive protocol encompassing: (1 structured questionnaire - Ocular Surface Disease Index (OSDI; (2 tear osmolarity (TearLab Osmolarity System - Ocusense; (3 tear film break-up time (TBUT; (4 fluorescein and lissamine green staining; (5 Schirmer test and (6 severity grading. RESULTS: One hundred and twenty five patients (aged 48.8 years-old ± 14.1, male:female ratio=0.4 were enrolled in the study, along with 24 age and gender matched controls. Higher scores on DED tests were obtained in Sjögren Syndrome (P<0.05, except for tear film osmolarity that was higher in diabetics (P<0.001 and fluorescein staining, that was higher in facial palsy (P<0.001. TFBUT and OSDI correlated better with other tests. The best combination of diagnostic tests for DED was OSDI, TBUT and Schirmer test (sensitivity 100%, specificity 95% and accuracy 99.3%. CONCLUSIONS: DED diagnostic test results present a broad range of variability among different conditions. Vital stainings and TBUT correlated best with one another whereas the best test combination to detect DED was: OSDI/TBUT/Schirmer.

  2. Etiologies of chronic liver disease in children

    Directory of Open Access Journals (Sweden)

    Farahmand F

    2001-11-01

    Full Text Available Chronic Liver diseases in children is the result of many different diseases including: metabolic, genetic, infectious, toxic and idiopathic causes. This was a case series study on 133 infants and children with age range 6 month to 12 years old, who presented clinically with manifestation of chronic liver disease and were admitted to Children Hospital Medical Center from year 1999 to 2000. In this study, 32 (24.5 percent patients had autoimmune chronic hepatitis, 15 (11.3 percent Glycogen storage diseases, 12 (9 percent extrahepatic biliary atresia, 11 (8.2 percent willson disease, 10 (7.5 percent cryptogenic cirrhosis, 6 (4.5 percent chronic hepatitis C, 5 (3.8 percen chronic hepatitic B, 5 (3.8 percent galactosemia 3 (2.25 percent congenital hepatic fibrosis, 3 (3.8 percent histiocytosis X, 3 (2.25 percent sclerosing cholangitis, 2 (1.5 percent byler’s disease 2 (1.5 percent primary tuberculosis, 1 (0.75 percent choledocalcyst, 1 (0.75 percent Alagyle syndrome. According to our data, chronic liver disease should be considered in infants and children. In our study, the most common causes are found to be: metabolic and genetic diseases (37.5 percent, chronic autoimmune hepatitis (24 percent and biliary disorders (14 percent, that encompass 86 percent of the patients.

  3. Imaging in Chronic Kidney Disease.

    Science.gov (United States)

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Chronic kidney disease (CKD) diagnosis and staging are based on estimated or calculated glomerular filtration rate (GFR), urinalysis and kidney structure at renal imaging techniques. Ultrasound (US) has a key role in evaluating both morphological changes (by means of B-Mode) and patterns of vascularization (by means of color-Doppler and contrast-enhanced US), thus contributing to CKD diagnosis and to the follow-up of its progression. In CKD, conventional US allows measuring longitudinal diameter and cortical thickness and evaluating renal echogenicity and urinary tract status. Maximum renal length is usually considered a morphological marker of CKD, as it decreases contemporarily to GFR, and should be systematically recorded in US reports. More recently, it has been found to be a significant correlation of both renal longitudinal diameter and cortical thickness with renal function. Conventional US should be integrated by color Doppler, which shows parenchymal perfusion and patency of veins and arteries, and by spectral Doppler, which is crucial for the diagnosis of renal artery stenosis and provides important information about intrarenal microcirculation. Different values of renal resistive indexes (RIs) have been associated with different primary diseases, as they reflect vascular compliance. Since RIs significantly correlate with renal function, they have been proposed to be independent risk factors for CKD progression, besides proteinuria, low GFR and arterial hypertension. Despite several new applications, US and color Doppler contribute to a definite diagnosis in <50% of cases of CKD, because of the lack of specific US patterns, especially in cases of advanced CKD. However, US is useful to evaluate CKD progression and to screen patients at risk for CKD. The indications and the recommended frequency of color Doppler US could differ in each case and the follow-up should be tailored. PMID:27170301

  4. Caregiver Burden in Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Murat Ilhan Atagun

    2011-09-01

    Full Text Available Duration of human life has been substantially increased in the last fifty years. Survivals of diseases have been prolonged through the advances in medicine. Together with these gratifying consequences, there appeared novel difficulties to cope with. Furthermore developments including globalization, industrialization and transition from rural to urban life occurred during the last century; so family units became smaller and numbers of members on employment in family units increased. As a result numbers of family members to undertake the responsibility of care decreased. As a concept, caregiver burden expresses physical, psychosocial and financial reactions during the course of care providing. Distinct factors including structures of social, cultural and family units and health care systems may affect conditions of care. Caregiver’s age, gender, ethnicity, education, relationship with the patient, attitude towards providing care, financial situation, coping abilities, her own health, beliefs, social support and cultural pattern are the personal factors that are related to perception of caregiver burden. Burden of care giving is geared to differential aspects of care needs. For instance care needs of physically disabled and medical care requiring patients with spinal cord injuries may differ from care needs of chronic psychiatric disorders, demented patients in advanced age of their lives or cancer patients in terminal periods. Strain due to care giving may differ as a result of properties of care demands. It is aimed to review the burden of caregivers in different medical and psychiatric care requiring conditions and to introduce differential aspects of caregiver burden in these different conditions.

  5. Rituximab, fludarabine, and total body irradiation as conditioning regimen before allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukemia: long-term prospective multicenter study.

    Science.gov (United States)

    Michallet, Mauricette; Socié, Gerard; Mohty, Mohamad; Sobh, Mohamad; Bay, Jacques-O; Morisset, Stéphane; Labussière-Wallet, Hélène; Tabrizi, Reza; Milpied, Noel; Bordigoni, Pierre; El-Cheikh, Jean; Blaise, Didier

    2013-02-01

    To evaluate the efficacy and toxicity of reduced-intensity conditioning (RIC) combining fludarabine, low-dose total body irradiation (TBI) and rituximab before allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leucocyte antigen (HLA) identical siblings, we conducted a prospective study in patients ≤65 years old with advanced chronic lymphocytic leukemia (CLL) stage B or C in response after a salvage treatment. Conditioning included rituximab (375 mg/m² on day 5), fludarabine (30 mg/m² from day 4 to day 2), TBI (2 Gy on day 0), and rituximab (500 mg/m² on days 1 and 8). Forty patients were included, 34 (85%) were male with a median age of 54 years (range, 35-65 years), 38 (95%) were in B stage, and 2 were in stage C; only 7 patients (17%) were in complete response. Seven (17%) patients did not receive rituximab. Thirty-nine (98%) patients engrafted, 17 patients developed acute graft-versus-host disease (GVHD) grade ≥II with a cumulative incidence at 3 months of 44% (36-52) with a significant protective effect of rituximab (p = 0.02). The cumulative incidence of chronic GVHD was 29% (21-36) at 12 months for both limited and extensive forms. The median overall survival was not reached with 5-years probability of 55% (41-74). The multivariate analysis showed a positive effect of rituximab on overall survival and event-free survival (hazard ratio [HR] = 0.1 [0-0.6], p = 0.02; and HR = 0.1 [0-0.4], p = 0.035, respectively). The association of fludarabine, TBI, and rituximab is feasible, well tolerated, and allows better outcomes in advanced CLL.

  6. HIV/AIDS, chronic diseases and globalisation

    OpenAIRE

    Colvin Christopher J

    2011-01-01

    Abstract HIV/AIDS has always been one of the most thoroughly global of diseases. In the era of widely available anti-retroviral therapy (ART), it is also commonly recognised as a chronic disease that can be successfully managed on a long-term basis. This article examines the chronic character of the HIV/AIDS pandemic and highlights some of the changes we might expect to see at the global level as HIV is increasingly normalised as "just another chronic disease". The article also addresses the ...

  7. Is acute recurrent pancreatitis a chronic disease?

    Institute of Scientific and Technical Information of China (English)

    Alberto Mariani; Pier Alberto Testoni

    2008-01-01

    Whether acute recurrent pancreaUtis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis.There is major evidence for considering alcoholic pancreatitis as a chronic disease ab initio while chronic pancreatitis lesions detectable in biliary acute recurrent pancreatitis (ARP) seem a casual association.Cystic fibrosis transmembrane con ductance regulator (CFTR) gene mutation,hereditary and obstructive pancreatitis seem an acute disease that progress to chronic pancreatitis,likely as a consequence of the activation and proliferation of pancreatic stellate cells that produce and activate collagen and therefore fibrosis.From the diagnostic point of view,in patients with acute recurrent pancreatitis Endoscopic ultrasound (EUS) seems the more reliable technique for an accurate evaluation and follow-up of some ductal and parenchymal abnormalities suspected for early chronic pancreatitis.

  8. [Chronic diseases. Definition and basic concept].

    Science.gov (United States)

    Raspe, H

    2011-01-01

    The baroque deity Chronos symbolizes much of what we intuitively connect with "chronic", but it must not obscure our view of the diversity of chronic diseases. Common to all forms is a prognostic implication: a chronic disease and all associated burden will accompany the patient for the rest of his/her life. Chronic diseases are in general multifocal disorders simultaneously affecting biological, psychic, and social equilibria. This requires systematic problem-screening and -assessment, including possible comorbidities. Comorbidity in a strict sense should be distinguished from risk factors, implications, complications, and consequences of the index disorder of interest. The assessment is usually followed by the shared identification of therapeutic goals and indications. In chronic disorders, a wide spectrum of diagnostic and therapeutic approaches, methods, and professions becomes relevant. PMID:21246322

  9. HIV/AIDS, chronic diseases and globalisation.

    Science.gov (United States)

    Colvin, Christopher J

    2011-08-26

    HIV/AIDS has always been one of the most thoroughly global of diseases. In the era of widely available anti-retroviral therapy (ART), it is also commonly recognised as a chronic disease that can be successfully managed on a long-term basis. This article examines the chronic character of the HIV/AIDS pandemic and highlights some of the changes we might expect to see at the global level as HIV is increasingly normalised as "just another chronic disease". The article also addresses the use of this language of chronicity to interpret the HIV/AIDS pandemic and calls into question some of the consequences of an uncritical acceptance of concepts of chronicity.

  10. HIV/AIDS, chronic diseases and globalisation

    Directory of Open Access Journals (Sweden)

    Colvin Christopher J

    2011-08-01

    Full Text Available Abstract HIV/AIDS has always been one of the most thoroughly global of diseases. In the era of widely available anti-retroviral therapy (ART, it is also commonly recognised as a chronic disease that can be successfully managed on a long-term basis. This article examines the chronic character of the HIV/AIDS pandemic and highlights some of the changes we might expect to see at the global level as HIV is increasingly normalised as "just another chronic disease". The article also addresses the use of this language of chronicity to interpret the HIV/AIDS pandemic and calls into question some of the consequences of an uncritical acceptance of concepts of chronicity.

  11. HIV/AIDS, chronic diseases and globalisation.

    Science.gov (United States)

    Colvin, Christopher J

    2011-01-01

    HIV/AIDS has always been one of the most thoroughly global of diseases. In the era of widely available anti-retroviral therapy (ART), it is also commonly recognised as a chronic disease that can be successfully managed on a long-term basis. This article examines the chronic character of the HIV/AIDS pandemic and highlights some of the changes we might expect to see at the global level as HIV is increasingly normalised as "just another chronic disease". The article also addresses the use of this language of chronicity to interpret the HIV/AIDS pandemic and calls into question some of the consequences of an uncritical acceptance of concepts of chronicity. PMID:21871074

  12. [Chronic inflammatory bowel diseases in cats].

    Science.gov (United States)

    Ghermai, A K

    1989-01-01

    The aetiology of chronic idiopathic intestinal inflammation is unknown. It is characterized by a diffuse infiltration with inflammatory cells into the intestinal mucosa and sometimes submucosa. Cats with chronic intermittent vomiting and diarrhoea, later on accompanied by anorexia and weight loss, are presented. Definitive diagnosis can be obtained by intestinal biopsy only. An immune pathogenesis is suspected, which is supported by the fact, that chronic inflammatory bowel disease responds to steroid therapy.

  13. A Review of Pediatric Chronic Kidney Disease.

    Science.gov (United States)

    Kaspar, C D W; Bholah, R; Bunchman, T E

    2016-01-01

    Chronic kidney disease is complex in both adults and children, but the disease is far from the same between these populations. Here we review the marked differences in etiology, comorbidities, impact of disease on growth and quality of life, issues unique to adolescents and transitions to adult care, and special considerations of congenital kidney and urinary tract anomalies for transplantation. PMID:26766175

  14. Membranous nephropathy and lupus-like syndrome after hematopoietic cell transplantation: a case report

    Directory of Open Access Journals (Sweden)

    Stylianou Kostas

    2010-09-01

    Full Text Available Abstract Introduction The kidney is increasingly recognised as a target organ of chronic graft-versus-host disease after hematopoietic cell transplantation in the context of the development of the nephrotic syndrome. Chronic graft-versus-host disease is associated with autoimmune phenomena similar, but not identical, to those observed in various rheumatologic disorders, implicating autoimmunity as an important component of the disease. Case presentation We report the case of a 57-year-old Caucasian man who developed the nephrotic syndrome due to membranous nephropathy in association with recurrent chronic graft-versus-host disease, along with a lupus-like syndrome manifested with pancytopenia, hair loss, positive anti-DNA antibodies and sub-epithelial and mesangial immune deposits. To the best of our knowledge, this is the first case reported in the literature. The nephrotic syndrome subsided soon after he was treated with a short course of cyclosporin with steroids. Unfortunately he died seven months later due to a relapse of leukemia. Conclusions Our case report confirms the notion that chronic graft-versus-host disease is characterized by the appearance of autoimmune phenomena similar, but not identical, to those seen in autoimmune diseases. The decision for more immunosuppression has to be weighed against the need for preservation of the graft versus leukemia phenomenon.

  15. Genetic influences on Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls; Thomsen, Simon F; Vestbo, Jørgen;

    2010-01-01

    Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted....

  16. Chronic Obstructive Pulmonary Disease in Women

    Directory of Open Access Journals (Sweden)

    Louis Laviolette

    2007-01-01

    Full Text Available BACKGROUND: Little is known about the comparative impact of chronic obstructive pulmonary disease (COPD between women and men and about women’s response to pulmonary rehabilitation.

  17. Percutaneous Nephrolithotomy and Chronic Kidney Disease

    DEFF Research Database (Denmark)

    Sairam, Krish; Scoffone, Cesare M; Alken, Peter;

    2012-01-01

    by glomerular filtration rate, including chronic kidney disease stages 0/I/II-greater than 60, stage III-30 to 59 and stages IV/V-less than 30 ml/minute/1.73 m(2). Patient characteristics, operative characteristics, outcomes and morbidity were assessed. RESULTS: Estimated glomerular filtration rate data were...... available on 5,644 patients, including 4,436 with chronic kidney disease stages 0/I/II, 994 with stage III and 214 with stages IV/V. A clinically significant minority of patients with nephrolithiasis presented with severe chronic kidney disease. A greater number of patients with stages IV/V previously...... underwent percutaneous nephrolithotomy, ureteroscopy or nephrostomy and had positive urine cultures than less severely affected patients, consistent with the higher incidence of staghorn stones in these patients. Patients with chronic kidney disease stages IV/V had statistically significantly worse...

  18. COPD (Chronic Obstructive Pulmonary Disease)

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is COPD? Español COPD, or chronic obstructive pulmonary (PULL-mun- ... can clog them. Normal Lungs and Lungs With COPD Figure A shows the location of the lungs ...

  19. Dispelling the chronic Lyme disease myth.

    Science.gov (United States)

    Kemperman, Melissa M; Bakken, Johan S; Kravitz, Gary R

    2008-07-01

    Lyme disease is a tick-borne illness endemic to Minnesota that can have potentially severe complications. As the incidence of Lyme disease continues to increase, it is important for physicians in Minnesota to become familiar with its clinical aspects, including the concept of "chronic Lyme disease." Chronic Lyme disease is a misnomer that is often applied to patients with nonspecific presentations who may or may not have a history of infection with Borrelia burgdorferi, the agent that causes Lyme disease. When a patient does present with persistent nonspecific symptoms attributed to chronic Lyme disease, clinicians should ascertain the presence of objective manifestations, obtain laboratory results, and get a history of tick exposure. If active infection with B. burgdorferi is unlikely, they should avoid prescribing empiric antibiotic therapy and instead thoroughly evaluate the patient for other possible causes of the complaints and recommend appropriate care.

  20. Chronic obstructive pulmonary disease : a proteomics approach

    OpenAIRE

    Alexandre, Bruno Miguel Coelho, 1980-

    2011-01-01

    Tese de doutoramento, Biologia (Biologia Molecular), Universidade de Lisboa, Faculdade de Ciências, 2012 Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation that is not fully reversible even under bronchodilators effect, caused by a mixture of small airway disease – obstructive bronchiolitis – and parenchymal destruction – emphysema. At the present time, COPD is the fourth leading cause of death and its prevalence and mortality are expected to contin...

  1. Asthma and chronic obstructive pulmonary disease overlap: asthmatic chronic obstructive pulmonary disease or chronic obstructive asthma?

    Science.gov (United States)

    Slats, Annelies; Taube, Christian

    2016-02-01

    Asthma and chronic obstructive pulmonary disease (COPD) are different disease entities. They are both clinical diagnoses, with diagnostic tools to discriminate between one another. However, especially in older patients (>55 years) it seems more difficult to differentiate between asthma and COPD. This has led to the definition of a new phenotype called asthma COPD overlap syndrome (ACOS). However, our understanding of ACOS is at a very preliminary stage, as most research has involved subjects with existing diagnoses of asthma or COPD from studies with different definitions for ACOS. This has led to different and sometimes opposing results between studies on several features of ACOS, also depending on the comparison with COPD alone, asthma alone or both, which are summarized in this review.We suggest not using the term ACOS for a patient with features of both asthma and COPD, but to describe a patient with chronic obstructive airway disease as completely as possible, with regard to characteristics that determine treatment response (e.g. eosinophilic inflammation) and prognosis (such as smoking status, exacerbation rate, fixed airflow limitation, hyperresponsiveness, comorbidities). This will provide a far more clinically relevant diagnosis, and would aid in research on treatment in more homogenous groups of patients with chronic airways obstruction. More research is certainly needed to develop more evidence-based definitions for this patient group and to evaluate biomarkers, which will help to further classify these patients, treat them more adequately and unravel the underlying pathophysiological mechanism. PMID:26596632

  2. Lung Compliance and Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    D. Papandrinopoulou

    2012-01-01

    Full Text Available Chronic obstructive pulmonary disease, namely, pulmonary emphysema and chronic bronchitis, is a chronic inflammatory response of the airways to noxious particles or gases, with resulting pathological and pathophysiological changes in the lung. The main pathophysiological aspects of the disease are airflow obstruction and hyperinflation. The mechanical properties of the respiratory system and its component parts are studied by determining the corresponding volume-pressure (P-V relationships. The consequences of the inflammatory response on the lung structure and function are depicted on the volume-pressure relationships.

  3. Small airways dysfunction in long-term survivors of pediatric stem cell transplantation

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Mathiesen, Sidsel; Buchvald, Frederik;

    2015-01-01

    BACKGROUND: Chronic graft-versus-host disease (cGvHD) in the lungs is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Pulmonary cGvHD is initiated in the peripheral airways, and diagnosis may be delayed by low sensitivity of standard pulmonary functio...

  4. Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options

    DEFF Research Database (Denmark)

    Uhlving, H H; Buchvald, F; Heilmann, C J;

    2012-01-01

    Bronchiolitis obliterans (BO) following allogeneic haematopoietic SCT (HSCT) is a serious complication affecting 1.7-26% of the patients, with a reported mortality rate of 21-100%. It is considered a manifestation of chronic graft-versus-host disease, but our knowledge of aetiology and pathogenesis...

  5. Chronic Kidney Disease and Its Complications

    OpenAIRE

    Thomas, Robert; Kanso, Abbas; Sedor, John R

    2008-01-01

    Chronic kidney disease (CKD) is a complex disease impacting more than twenty million individuals in the United States. Progression of CKD is associated with a number of serious complications, including increased incidence of cardiovascular disease, hyperlipidemia, anemia and metabolic bone disease. CKD patients should be assessed for the presence of these complications and receive optimal treatment to reduce their morbidity and mortality. A multidisciplinary approach is required to accomplish...

  6. The chronic gastrointestinal manifestations of Chagas disease

    Directory of Open Access Journals (Sweden)

    Nilce Mitiko Matsuda

    2009-01-01

    Full Text Available Chagas disease is an infectious disease caused by the protozoan Trypanosoma cruzi. The disease mainly affects the nervous system, digestive system and heart. The objective of this review is to revise the literature and summarize the main chronic gastrointestinal manifestations of Chagas disease. The chronic gastrointestinal manifestations of Chagas disease are mainly a result of enteric nervous system impairment caused by T. cruzi infection. The anatomical locations most commonly described to be affected by Chagas disease are salivary glands, esophagus, lower esophageal sphincter, stomach, small intestine, colon, gallbladder and biliary tree. Chagas disease has also been studied in association with Helicobacter pylori infection, interstitial cells of Cajal and the incidence of gastrointestinal cancer.

  7. Circulating Adipocytokines and Chronic Kidney Disease

    OpenAIRE

    Mills, Katherine T.; L Lee Hamm; A Brent Alper; Chad Miller; Alhakam Hudaihed; Saravanan Balamuthusamy; Chung-Shiuan Chen; Yanxi Liu; Joseph Tarsia; Nader Rifai; Myra Kleinpeter; Jiang He; Jing Chen

    2013-01-01

    BACKGROUND: Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD), but their relationship with CKD has not been well characterized. METHODS: We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR)

  8. The Western Diet and Chronic Kidney Disease.

    Science.gov (United States)

    Hariharan, Divya; Vellanki, Kavitha; Kramer, Holly

    2015-03-01

    Characteristics of the Western diet that fueled the obesity epidemic may also impact kidney disease incidence and progression. Enlarging portion sizes over the past half century has been accompanied by increased intake of protein, sodium, and processed foods while consumption of fruits and vegetables has declined. Overall dietary patterns play a strong role for chronic disease risk including chronic kidney disease. While dietary patterns high in fresh fruits and vegetables and low in red meats, such as the Mediterranean diet, decrease the risk of chronic diseases, the Western diet, characterized by high intake of red meat, animal fat, sweets, and desserts and low intake of fresh fruits and vegetables and low-fat dairy products, increases risk of chronic diseases. In this article, we review the potential mechanisms whereby several key characteristics of the typical Western diet may impact kidney disease incidence and progression. We also discuss a public health policy initiative to improve dietary choices. Reducing protein intake to the recommended daily allowance of 0.8 g/kg/day and increasing intake of fruit and vegetables and fiber may mitigate kidney disease progression and reduce risk of cardiovascular disease and mortality. PMID:25754321

  9. Chronic Wasting Disease Agents in Nonhuman Primates

    OpenAIRE

    Race, Brent; Meade-White, Kimberly D.; Phillips, Katie; Striebel, James; Race, Richard; Chesebro, Bruce

    2014-01-01

    Chronic wasting disease is a prion disease of cervids. Assessment of its zoonotic potential is critical. To evaluate primate susceptibility, we tested monkeys from 2 genera. We found that 100% of intracerebrally inoculated and 92% of orally inoculated squirrel monkeys were susceptible, but cynomolgus macaques were not, suggesting possible low risk for humans.

  10. Chronic kidney disease - pediatric risk factors.

    Science.gov (United States)

    Tasic, Velibor; Janchevska, Aleksandra; Emini, Nora; Sahpazova, Emilija; Gucev, Zoran; Polenakovic, Momir

    2016-01-01

    The knowledge about the progression of chronic kidney disease is an important issue for every pediatric nephrologist and pediatrician in order to implement appropriate measures to prevent wasting of renal function and the final consequence - end stage renal disease with the need for the dialysis and transplantation. Therefore it is important to know, treat or ameliorate the standard risk factors such as hypertension, proteinuria, anemia, hyperparathyroidism etc. In this review devoted to the World Kidney Day 2016 we will pay attention to the low birth parameters, obesity, hyperuricemia and smoking which emerged as particularly important risk factors for children and adolescent with chronic kidney disease. PMID:27442412

  11. Trace elements and chronic liver diseases

    Energy Technology Data Exchange (ETDEWEB)

    Loguercio, C.; De Girolamo, V.; Federico A., A.; Del Vecchio Blanco, C. [Seconda Universita di Napoli, Naples (Italy). Cattedra di Gastroenterologia; Feng, S.L.; Gialanella, G. [Naples Univ. (Italy). Dipt. di Scienze Fisiche; Cataldi, V. [Naples Univ. (Italy). Prima Medicina Ospedale Ascalesi

    1997-12-31

    The relationships between chronic liver diseases and trace element (TE) contents are debated. Particularly, no defined data are available about the TE levels in viral liver disease patients with or without malnutrition. In this study we evaluated blood and plasma levels of various trace elements in patients with HCV-related chronic liver disease, at different stages of liver damage (8 patients with chronic hepatitis and 32 with liver cirrhosis) with or without malnutrition. We also studied 10 healthy volunteers as control group. We found that cirrhotic subjects had a significant decrease of blood levels of Zn and Se, independently on the nutritional status, whereas plasma levels of Fe were significantly reduced only in malnourished cirrhotic patients. Our data indicate that liver impairment is the main cause of the blood decrease of Se and Zn levels in patients with non alcoholic liver disease, whereas the malnutrition affects Fe levels only. (orig.)

  12. 异基因造血干细胞移植后人类疱疹病毒6型活化与急性移植物抗宿主病的相关性研究%Correlation between human herpesvirus 6 activation and acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    王立茹; 董陆佳; 陆道培

    2006-01-01

    目的 研究造血干细胞移植(HSCT)后人类疱疹病毒6型(HHV-6)活化与急性移植物抗宿主病(aGVHD)的相关性.方法 移植前以及移植后每周1次连续采集72例患者的外周血样本,采用筑巢式聚合酶链反应扩增HHV-6基因序列,Hind Ⅲ酶切对HHV-6基因分型.结果 72例患者移植后45例(62.5%)检出HHV-6 血症,中位时间为第14(7~63)天;40例(55.6%)患者发生Ⅰ~Ⅳ度aGVHD,中位时间第26(9~73)天.HHV-6血症发生的中位时间显著早于Ⅰ~Ⅳ度aGVHD发生时间(P=0.018).Ⅰ~Ⅳ度aGVHD累积发生率在HHV-6阳性组为68.9%(45例中31例),显著高于HHV-6阴性组的33.3%(27例中9例)(P=0.003).Ⅱ~Ⅳ度aGVHD累积发生率HHV-6阳性组为35.6%,显著高于HHV-6阴性组的14.8%(P=0.027).移植后Ⅰ~Ⅳ度aGVHD的发生率在巨细胞病毒(CMV)和HHV-6共感染(CMV+/HHV-6+)组、CMV阳性HHV-6阴性(CMV+/HHV-6-)组、CMV阴性HHV-6阳性(CMV-/HHV-6+)组和CMV与HHV-6均阴性(CMV/HHV-6-)组分别为78.9%,55.6%,14.3%和22.2%,差异有统计学意义(P=0.0001).Ⅱ~Ⅳ度aGVHD累积发生率在CMV+/HHV-6+、CMV+/HHV-6-、CMV-/HHV-6+和CMV-/HHV-6-组分别为42.1%,22.2%,0%和11.1%,差异有统计学意义(P=0.008).结论 HSCT后HHV-6感染以及HHV-6和CMV共感染与aGVHD发生率存在显著相关性.

  13. Relationship Between CCR5 and Acute Graft-Versus-Host Disease in Murine Bone Marrow Transplantation%在小鼠骨髓移植中CCR5与急性移植物抗宿主病的相关性研究

    Institute of Scientific and Technical Information of China (English)

    王昭; William J.Murphy

    2006-01-01

    This study was aimed to eveluate the role of CCR5 on donor cells in recipient models received intensive conditioning, so as provide the scientific evidence for clinical application of allo-HSCT. Lethally irradiated BALB/cmice received allogeneic bone marrow transplants from C57BL/6 mice. Mice divided into 4 groups according to receiving variant donor cells: B6 CCR5 KO group, receiving C57BL/6 CCR5 -/- mice bone marrow cells and splenocytes; B6 WT BMC group, receiving C57BL/6 mice bone marrow cells and splenocytes; B6 CCR5 KO BMC group, receiving C57BL/6 CCR5 -/ bone marrow cells alone; B6 WT BMC group, receiving C57BL/6 mice bone marrow cells alone.The result showed that compared to B6 WT BMC group, B6 CCR5 KO group succumbed to acute GVHD at an accelerated rate. Donor CD8 + T cells expanded to a significantly greater extent in recipients of CCR5 KO, compared with B6 WT control cells. T cells recovered from recipients of CCR5 KO cells produced more IFN-γ and TNF-α and proliferated to a T-cell at a significantly higher level than T cells from recipients of WT cells, indicating that CCR5 plays a role in downregualting donor alloreative CD8 + T-cells expansion. Histological assessment of the mice indicated pathological le sions in the kidneys and a greater degree of liver pathological changes in mice that received CCR5 KO donor grafts. It is concluded that the knock-out of CCR5 on donor cells results in increase of GVHD and donor CD8 + T cell expansion, as well as hepatic and renal lesions in allo-HSCT, which indicates that CCR5 is very important in allo-BMT.%本研究评价供者CCR5在经过强化预处理的骨髓移植动物模型受者体内的作用,为今后的异基因造血干细胞移植的临床应用提供科学依据.经过致死剂量照射的BALB/c小鼠接受异基因C57BL/6小鼠的骨髓移植.根据回输的细胞不同实验分为4组:B6 CCR5 KO组,受者接受C57BL/6 CCR5-/-小鼠骨髓和脾脏细胞;B6 WT组,受者接受野生型C57BL/6小鼠骨髓和脾脏细胞;B6 CCR5 KO BMC组,受者只接受C57BL/6 CCR5-/-小鼠骨髓细胞;B6 WT BMC组,受者只接受野生型C57BL/6小鼠骨髓细胞.结果表明:较之B6 WT组,B6 CCR5 KO组小鼠以更快的速度死于急性GVHD;其受者体内的CD8+T细胞更大量的增殖;其T细胞恢复后产生更多的INF-γ和TNF-α并且由于其T细胞有丝分裂原刀豆素水平处于较高水平,从而进一步促进T细胞的增殖,提示CCR5的作用之一是下调参与排异反应的供者CD8+T细胞的增殖.组织学评价提示,移植剔除CCR5基因受者细胞的小鼠肾脏出现了病理损伤并且肝脏存在有更为严重的病理变化.结论:剔除CCR5基因的异基因骨髓移植使GVHD发病率的增加,供者CD8+T细胞在受者体内增殖增加以及肝肾损害加重,这提示CCR5在异基因骨髓移植中起着重要作用.

  14. Establishment and Pathophysiology Study of Allogeneic Bone Marrow Transplantation Model for Graft-Versus-Host Disease%同种异基因骨髓移植GVHD动物模型的建立及其病理生理学机制初探

    Institute of Scientific and Technical Information of China (English)

    刘杰; 王永安; 钱远宇; 孟庆义

    2009-01-01

    目的:建立稳定的异基因骨髓移植GVHD(移植物抗宿主病)动物模型,并初步了解其病理生理学机制.方法:以BALB/c(H-2d)雌性小鼠为受者,接受8 Gy致死剂量的60Co.全身照射后,输注雄性C57BL/6(H-2b)供鼠的脾细胞和骨髓细胞.观察受鼠的体征、造血功能恢复及生存时问的变化,并进行病理学、嵌合体和T细胞亚群及相关细胞因子的检查.结果:模型组小鼠在移植后出现了典型的GVHD症状;肠、肝、脾、皮肤的病理学分析均属于Ⅳ度GVHD;嵌合体植入成功;以7、14和21 d为检测时间点,发现模型组鼠体内T细胞亚群移植后较移植前CD3+CD4+T细胞数量减少,CD3+CD8+T细胞显著升高,CD4+和CD8+T细胞比例严重倒置,随着时间变化比值会逐渐升高,但仍然处于较显著的倒置水平;血清中IFN-y、TNF-a在移植后+7 d表达显著增高,尤其是IFN-V的表达在+7 d达峰值;IL-4和IL-10的水平在移植前后几乎没有变化.结论:建立了稳定的GVHD动物模型;此模型发病过程中,CD8+T细胞介导的CTL细胞毒性作用可能要大于CD4+Th介导的细胞因子效应;IFN-y、TNF-a炎症因子在GVHD的早期发挥重要作用;IL-4、IL-10的低水平分泌与急性GVHD的高发病率有关.

  15. Associação dos níveis de citocinas no pós-transplante de células-tronco hematopoiéticas com a Doença do Enxerto Contra o Hospedeiro aguda Association of cytokine levels with acute graft versus host disease following full match allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Jeane E. L. Visentainer

    2005-09-01

    Full Text Available Este estudo foi realizado para investigar se os níveis séricos de sIL-2R, TNF-alfa, IFN-gama, IL-6, IL-10 e TGF-beta1 estavam associados com o desenvolvimento de DECH (Doença do Enxerto Contra o Hospedeiro aguda. Os níveis de citocinas foram seqüencialmente mensurados por Elisa em 13 pacientes que haviam sido submetidos ao transplante alogênico de células progenitoras hematopoiéticas. Os níveis de sIL-2R e IL-10 da 1ª a 15ª semanas pós-transplante foram significativamente maiores no grupo que desenvolveu DECH aguda que naquele sem a doença. Os níveis de sIL-2R aumentaram em direta correlação com a pega do enxerto e ao tempo do DECH aguda, enquanto os níveis de IL-10 aumentaram transitoriamente pós-transplante. A média da concentração de TNF-alfa nas primeiras semanas após o transplante foi maior no grupo que desenvolveu DECH aguda. Além disso, uma queda dos níveis de TGF-beta1 após a pega esteve significativamente associada à DECH aguda. Nenhuma correlação foi encontrada entre DECH aguda e as outras citocinas investigadas. Estes resultados suportam a idéia de que um balanço entre as citocinas derivadas de linfócitos T auxiliadores do tipo 1 e 2 pode ser importante no desenvolvimento e controle da DECH aguda. Embora os níveis de sIL-2R, TNF-alfa, IL-10 e TGF-beta1 tenham sido correlacionados com a DECH aguda, os níveis de sIL-2R ao tempo da pega podem prover um melhor parâmetro para a detecção precoce de DECH aguda após o transplante alogênico.This study was performed to investigate whether the serum levels of sIL-2R, TNF-alpha, IFN-gamma, IL-6, IL-10, and TGF-beta1 are associated with the development of acute GVHD. Serum cytokine levels were sequentially measured by sandwich Enzyme Linked-Immuno-Sorbent Assay (Elisa in 13 patients who had received full match allogeneic stem cell transplantation. Serum sIL-2R and IL-10 levels from the 1st to the 15th week post transplantation were significantly higher in the group who developed acute GVHD than in the group without acute GVHD. Soluble IL-2R levels increased in direct correlation to engraftment and onset of acute GVHD, while IL-10 levels increased transiently following transplantation. The mean TNF-alpha concentration in the first weeks after transplantation was augmented in the group that developed acute GVHD. Furthermore, a drop in TGF-beta1 levels after the engraftment was significantly associated to acute GVHD. No correlation was found between acute GVHD and the other evaluated cytokines. These results support the idea that a balance between cytokines derived from type 1 and type 2 T-helper cells may be important in the development and control of acute GVHD. Although sIL-2R, TNF-alpha, IL-10, and TGF-beta1 levels, correlated with acute GVHD, sIL-2R levels at the engraftment may provide a better parameter for the early detection of acute GVHD after allogeneic stem cell transplantation.

  16. 芳香烃受体在免疫系统及移植物抗宿主病(GVHD)中的研究进展%Research progression of Aryl hydrocarbon receptor in the immune system and graft-versus-host disease (GVHD)

    Institute of Scientific and Technical Information of China (English)

    丁萍; 陈黎; 张铀

    2015-01-01

    芳香烃受体(aryl hydrocarbon receptor,AhR)是一种介导芳香烃类化合物毒性反应的蛋白质.另外,它也参与一些重要的生物学过程.目前AhR在免疫系统中的作用日益受到学者们的关注.AhR能以配体依赖的方式调节初始T细胞(naive T cells)向调节性T细胞(Regulatory T cells,Tregs)和辅助性T17细胞(T-helper 17 cells,Th17)分化,从而调节免疫反应,并能抑制GVHD的发生.本文试图阐明目前已知的关于AhR的生物学及AhR调节免疫反应的机制,并对未来研究AhR在人类免疫及相关疾病中的作用有指导意义.

  17. Exploring metabolic dysfunction in chronic kidney disease

    OpenAIRE

    Slee Adrian D

    2012-01-01

    Abstract Impaired kidney function and chronic kidney disease (CKD) leading to kidney failure and end-stage renal disease (ESRD) is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD) risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabol...

  18. Relationship between acute and chronic disease epidemiology.

    OpenAIRE

    Kuller, L.H. (Lewis H.)

    1987-01-01

    Epidemiology is the study of epidemics. The primary goal of epidemiological studies should be the identification of the determinants of disease in order to decrease morbidity and mortality. Epidemiological studies evolve through descriptive, analytical, and experimental approaches. The traditional infectious disease epidemiology studies were primarily concerned with identification of an agent, incubation period, mode of transmission, population at risk, and methods of disease control. Chronic...

  19. Diphenylhydantoin (phenytoin)-induced chronic pulmonary disease

    OpenAIRE

    Dixit Ramakant; Dixit Kalpana; Nuwal Paras; Banerjee Arunima; Sharma Sidharth; Dave Lokendra

    2009-01-01

    Drug-induced respiratory diseases are difficult to diagnose and therefore usually not identified, probably underestimated and under-reported. We report a case of diphenylhydantoin/phenytoin-induced chronic pulmonary disease in a 62-year-old male patient presenting with progressive dyspnea, eosinophilia, and pulmonary abnormalities. The importance of drug history in clinical history-taking and early diagnosis of drug-induced respiratory diseases is emphasized so as to prevent permanent pulmona...

  20. Cardiovascular disease in patients with chronic kidney disease

    OpenAIRE

    Julian Wright; Alastair Hutchison

    2009-01-01

    Julian Wright, Alastair HutchisonManchester Institute of Nephrology and Transplantation, Manchester Royal Infirmary, Manchester, UKAbstract: Patients with chronic kidney disease have a high burden of cardiovascular morbidity and mortality. The vast majority of patients with chronic kidney disease do not progress to end stage renal failure, but do have a significantly higher incidence of all cardiovascular co-morbidities. Traditional cardiovascular risk factors only partially account for this ...

  1. Dynamic Adaptive Remote Health Monitoring for Patients with Chronic Disease

    OpenAIRE

    Suh, Myung-kyung

    2012-01-01

    Chronic diseases are the leading causes of death and disability in the United States. More than 70% of deaths among Americans are caused by chronic diseases and more than 133 million Americans have at least one chronic disease. Due to the prevalence of chronic disease-related issues, it is prudent to seek out methodologies that would facilitate the prevention, monitoring, and feedback for patients with chronic diseases.This dissertation describes WANDA (Weight and Activity with Other Vital Si...

  2. Framing international trade and chronic disease

    Directory of Open Access Journals (Sweden)

    Mohindra Katia S

    2011-07-01

    Full Text Available Abstract There is an emerging evidence base that global trade is linked with the rise of chronic disease in many low and middle-income countries (LMICs. This linkage is associated, in part, with the global diffusion of unhealthy lifestyles and health damaging products posing a particular challenge to countries still facing high burdens of communicable disease. We developed a generic framework which depicts the determinants and pathways connecting global trade with chronic disease. We then applied this framework to three key risk factors for chronic disease: unhealthy diets, alcohol, and tobacco. This led to specific 'product pathways', which can be further refined and used by health policy-makers to engage with their country's trade policy-makers around health impacts of ongoing trade treaty negotiations, and by researchers to continue refining an evidence base on how global trade is affecting patterns of chronic disease. The prevention and treatment of chronic diseases is now rising on global policy agendas, highlighted by the UN Summit on Noncommunicable Diseases (September 2011. Briefs and declarations leading up to this Summit reference the role of globalization and trade in the spread of risk factors for these diseases, but emphasis is placed on interventions to change health behaviours and on voluntary corporate responsibility. The findings summarized in this article imply the need for a more concerted approach to regulate trade-related risk factors and thus more engagement between health and trade policy sectors within and between nations. An explicit recognition of the role of trade policies in the spread of noncommunicable disease risk factors should be a minimum outcome of the September 2011 Summit, with a commitment to ensure that future trade treaties do not increase such risks.

  3. Transcending chronic liver disease: a qualitative study.

    Science.gov (United States)

    Wainwright, S P

    1997-01-01

    This study explores and describes experiences of chronic liver disease from the patient's perspective. No qualitative research studies appear to have examined the experiences of these patients. In-depth focused interviews and grounded theory data collection and data analysis methods were used. A two-stage theoretical framework (becoming ill, and not living) of the experience of transcending chronic liver disease is presented. Sociological and psychological literature on common sense models of health and illness are briefly reviewed. Several suggestions for further research are made. The way in which this qualitative research study is leading to a quantitative and qualitative appraisal of the psychological adjustment in end-stage chronic liver disease patients is outlined.

  4. Management of Pruritus in Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Angeline Bhalerao

    2015-01-01

    Full Text Available Background. There continues to be uncertainty on the ideal treatment of pruritus in chronic liver disease. The aim of this study was to gather the latest information on the evidence-based management of pruritus in chronic liver disease. Methodology. A literature search for pruritus in chronic liver disease was conducted using Pubmed and Embase database systems using the MeSH terms “pruritus,” “chronic liver disease,” “cholestatic liver disease,” and “treatment.” Results. The current understanding of the pathophysiology of pruritus is described in addition to detailing research into contemporary treatment options of the condition. These medical treatments range from bile salts, rifampicin, and opioid receptor antagonists to antihistamines. Conclusion. The burden of pruritus in liver disease patients persists and, although it is a common symptom, it can be difficult to manage. In recent years there has been greater study into the etiology and treatment of the condition. Nonetheless, pruritus remains poorly understood and many patients continue to suffer, reiterating the need for further research to improve our understanding of the etiology and treatment for the condition.

  5. Chronic Disease Cost not Transferable: Colombian Reality

    Directory of Open Access Journals (Sweden)

    Karina Gallardo Solarte

    2016-01-01

    Full Text Available Objective: The aim is to reflect on the social and economic costs of chronic non-communicable disease (NCD in Colombia to display a charging indicator of these pathologies. Material and methods: In a review of 50 studies, 27 were selected since these met the inclusion criteria, like chronical disease, studies conducted between 2002 and 2011 related to costs, chronic disease, and being Colombian. Results: This is a review study of chronic diseases vs. their costs, being here cardiovascular diseases part of the group of high cost and higher incidence diseases, thus repre­senting a great risk to the financial stability of healthcare companies. There are few studies that address the costs generated by the treatment of ncds patients that show the economic impact experienced by public and private institutions providing and promoting health services. Most of them forget the economic, family and social costs the affected population must suffer. Conclu­sions: ncds represent a burden to the health service system for their very high costs, untimely intervention and reduced significant benefit for this population and their families.

  6. Chronic Obstructive Pulmonary Disease (COPD)

    Science.gov (United States)

    ... learn about your disease, receive counseling, and create exercise and eating plans tailored to your needs. Surgery: Rarely, patients who have very serious COPD may benefit from surgery. They might have a lung reduction ...

  7. Quality of life in chronic disease patients

    Directory of Open Access Journals (Sweden)

    Kalliopi Megari

    2013-09-01

    Full Text Available During the past decades there was an increasing predominance of chronic disorders, with a large number of people living with chronic diseases that can adversely affect their quality of life. The aim of the present paper is to study quality of life and especially Health-related quality of life (HRQoL in chronic diseases. HRQOL is a multidimensional construct that consists of at least three broad domains − physical, psychological, and social functioning − that are affected by one’s disease and/or treatment. HRQoL is usually measured in chronic conditions and is frequently impaired to a great extent. In addition, factors that are associated with good and poor HRQoL, as well as HRQoL assessment will be discussed. The estimation of the relative impact of chronic diseases on HRQoL is necessary in order to better plan and distribute health care resources aiming at a better HRQoL.[«All the people perceive the concept of living good or being well, that is the same as being happy». (Aristotle. 384-322 BC. Ethica Nichomachea

  8. Autoimmune thyroid disease and chronic urticaria.

    Science.gov (United States)

    Monge, Cecilia; Demarco, Paul; Burman, Kenneth D; Wartofsky, Leonard

    2007-09-01

    We report six cases of autoimmune thyroid disease associated with chronic urticaria and briefly review the literature, including the histopathological nature of such lesions, and their aetiology and pathogenesis. In view of the prevalence of thyroid disease in patients with chronic urticaria, screening measurements of thyrotropin and anti-thyroperoxidase antibodies are recommended, although negative antibodies do not exclude a relationship between urticaria and thyroid autoimmunity. After failure of conventional therapy for urticaria, patients who are apparently clinically euthyroid may be considered for a trial with levothyroxine. Improvement of urticaria was seen with levothyroxine treatment in three of four patients with only marginal abnormalities in thyroid function.

  9. Anemia in Chronic Kidney Disease

    Science.gov (United States)

    ... Disease Organizations​​ . (PDF, 345 KB)​​​​​ Alternate Language URL Anemia in CKD Page Content On this page: What ... Nutrition Points to Remember Clinical Trials What is anemia? Anemia is a condition in which the body ...

  10. Adult stem cells for chronic lung diseases.

    Science.gov (United States)

    Mora, Ana L; Rojas, Mauricio

    2013-10-01

    Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lung diseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lung diseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow-derived mesenchymal stem cells (B-MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B-MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B-MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B-MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF. PMID:23648014

  11. An Update on Coronary Artery Disease and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Baris Afsar

    2014-01-01

    Full Text Available Despite the improvements in diagnostic tools and medical applications, cardiovascular diseases (CVD, especially coronary artery disease (CAD, remain the most common cause of morbidity and mortality in patients with chronic kidney disease (CKD. The main factors for the heightened risk in this population, beside advanced age and a high proportion of diabetes and hypertension, are malnutrition, chronic inflammation, accelerated atherosclerosis, endothelial dysfunction, coronary artery calcification, left ventricular structural and functional abnormalities, and bone mineral disorders. Chronic kidney disease is now recognized as an independent risk factor for CAD. In community-based studies, decreased glomerular filtration rate (GFR and proteinuria were both found to be independently associated with CAD. This paper will discuss classical and recent epidemiologic, pathophysiologic, and clinical aspects of CAD in CKD patients.

  12. A Customizable Model for Chronic Disease Coordination: Lessons Learned From the Coordinated Chronic Disease Program.

    Science.gov (United States)

    Voetsch, Karen; Sequeira, Sonia; Chavez, Amy Holmes

    2016-01-01

    In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managed resources, and 6) relationship building. These elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs. PMID:27032986

  13. Severe chronic allergic (and related) diseases

    DEFF Research Database (Denmark)

    Bousquet, J; Anto, J M; Demoly, P;

    2012-01-01

    and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.......-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic...... and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness...

  14. Multiple Bowen's disease in chronic arsenicosis

    Directory of Open Access Journals (Sweden)

    Joydeep Singha

    2014-04-01

    Full Text Available Bowen’s disease is a carcinoma in-situ of skin. It was fi rst described by John T. Bowen. It usually present as a solitary lesion in elderly person over sun-exposed area. A case of multiple Bowen’s disease involving non-sun exposed areas of a person with clinical sign of chronic arsenicosis has been found.Read more....

  15. Multiple Bowen's disease in chronic arsenicosis

    OpenAIRE

    Joydeep Singha

    2014-01-01

    Bowen’s disease is a carcinoma in-situ of skin. It was fi rst described by John T. Bowen. It usually present as a solitary lesion in elderly person over sun-exposed area. A case of multiple Bowen’s disease involving non-sun exposed areas of a person with clinical sign of chronic arsenicosis has been found.Read more....

  16. Exacerbations of Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Garvey, Christine; Ortiz, Gabriel

    2012-01-01

    Epidemiologic data indicate that chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Patients with poorly managed COPD are likely to experience exacerbations that require emergency department visits or hospitalization—two important drivers contributing to escalating healthcare resource use and costs associated with the disease. Exacerbations also contribute to worsening lung function and negative outcomes in COPD. The aim of this review is to present th...

  17. Hypertension and chronic kidney disease in Turkey

    OpenAIRE

    Sengul, Sule; Erdem, Yunus; Batuman, Vecihi; Erturk, Sehsuvar

    2013-01-01

    Worldwide, both hypertension and chronic kidney disease are major public health problems, due to their epidemic proportions and their association with high cardiovascular mortality. In 2003, the first Prevalence, awareness, treatment, and control of hypertension in Turkey (the PatenT) study was conducted in a nationally representative population (n=4910) by the Turkish Society of Hypertension and Renal Diseases, and showed that overall age- and sex-adjusted prevalence of hypertension in Turke...

  18. Interleukin-10 and chronic liver disease

    OpenAIRE

    ZHANG, LI-JUAN; Wang, Xiao-Zhong

    2006-01-01

    Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many cell populations. Numerous investigations suggest that IL-10 plays a major role in chronic liver diseases. IL-10 gene polymorphisms are possibly associated with liver disease susceptibility or severity. Recombinant human IL-10 has been produced and is currently tested in clinical trials. These trials may give new insights into the immunobiology of IL-10 and suggest that the IL-10/IL-10 receptor system may become a ...

  19. Interleukin-10 and chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Li-Juan Zhang; Xiao-Zhong Wang

    2006-01-01

    Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many cell populations. Numerous investigations suggest that IL-10 plays a major role in chronic liver diseases. IL-10 gene polymorphisms are possibly associated with liver disease susceptibility or severity. Recombinant human IL-10 has been produced and is currently tested in clinical trials. These trials may give new insights into the immunobiology of IL-10 and suggest that the IL-10/IL-10 receptor system may become a new therapeutic target.

  20. Chronic obstructive pulmonary disease and cancer risk

    DEFF Research Database (Denmark)

    Kornum, Jette Brommann; Sværke, Claus; Thomsen, Reimar Wernich;

    2012-01-01

    Little is known about the risk of cancer in patients with chronic obstructive pulmonary disease (COPD), including which cancer sites are most affected. We examined the short- and long-term risk of lung and extrapulmonary cancer in a nationwide cohort of COPD patients....

  1. Anemia of Inflammation and Chronic Disease

    Science.gov (United States)

    ... 699–710. 4 Anemia of Inflammation and Chronic Disease Eating, Diet, and Nutrition People with anemia caused by ... Phone: 202–776–0544 Fax: 202–776–0545 Internet: www. hematology. org Iron Disorders Institute P.O. Box 675 Taylors, SC 29687 ...

  2. Screening of Elderly for Chronic Kidney Disease

    NARCIS (Netherlands)

    Lezaic, Visnja; Bajcetic, Sanja; Perunicic-Pekovic, Gordana; Bukvic, Danica; Dimkovic, Nada; Djukanovic, Ljubica

    2012-01-01

    Background and Aims: The frequency of chronic kidney disease (CKD) markers was assessed in two groups of patients over 60 years - one without and the other with hypertension. Methods: The cross-sectional study involved 585 asymptomatic elderly patients (227 males), 93 without and 492 with hypertensi

  3. Living With Chronic Lower Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Charlotte Pooler

    2014-09-01

    Full Text Available In this article, I present a phenomenological study of individuals’ experiences of living with moderate to very severe chronic lower pulmonary disease (chronic obstructive pulmonary disease, asthma, or both. Phenomenology is a philosophy, distinct from descriptive or thematic research, which is useful as a foundation for scientific inquiry. In this study, I used the lens of Merleau-Ponty to understand and interpret participants’ experiences of living with pulmonary disease, and the approach of van Manen for analysis. I conclude that in chronic pulmonary disease, awareness of breathing and the body is experienced in the sounds, sensations, and signals of breathing and the body, and in the experiences of the body-in-the-world. Central themes of being-in-the-world from the study describe the disruption of the embodied phenomenological self: Participants experienced slowing down, doing less, and having to stop due to shortness of breath. Both chronic and acute dyspnea were prevalent and the taken-for-granted aspects of daily activities were disrupted. Findings of this study have implications for public and patient education, and opportunities for integration of experiential aspects within nursing education and practice.

  4. Osteoporosis Associated with Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Okazaki, Ryo; Watanabe, Reiko; Inoue, Daisuke

    2016-08-01

    Recent epidemiological studies have revealed that osteoporosis is closely associated with common chronic diseases including diabetes, hypertension, chronic kidney disorders, and chronic obstructive pulmonary disease (COPD). COPD is a chronic inflammatory airway disease but now well known to be associated with various systemic comorbidities including osteoporosis. Osteoporosis and osteoporotic fractures are extremely common in COPD patients, which have significant impacts on their quality of life (QOL), activities of daily life (ADL), respiratory function, and possibly their prognosis. COPD-associated osteoporosis is however extremely under-recognized, hence undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality compromise bone strength causing fractures in COPD. In COPD patients, various general clinical risk factors for osteoporosis are present including smoking, older age, low body weight, and physical inactivity. In addition, disease-related risk factors such as decreased pulmonary function, inflammation, glucocorticoid use and vitamin D deficiency/insufficiency have been linked to the development of osteoporosis in COPD. Increased awareness of osteoporosis in COPD, especially that of high prevalence of vertebral fractures is called upon among general physicians as well as pulmonologists. Routine screening for osteoporosis and risk assessment of fractures will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage. Timely prevention of developing osteoporosis together with appropriate treatment of established osteoporosis may improve QOL and ADL of the COPD patients, preserve their lung function and eventually result in better prognosis in these patients. PMID:27622174

  5. Osteoporosis Associated with Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Watanabe, Reiko; Inoue, Daisuke

    2016-01-01

    Recent epidemiological studies have revealed that osteoporosis is closely associated with common chronic diseases including diabetes, hypertension, chronic kidney disorders, and chronic obstructive pulmonary disease (COPD). COPD is a chronic inflammatory airway disease but now well known to be associated with various systemic comorbidities including osteoporosis. Osteoporosis and osteoporotic fractures are extremely common in COPD patients, which have significant impacts on their quality of life (QOL), activities of daily life (ADL), respiratory function, and possibly their prognosis. COPD-associated osteoporosis is however extremely under-recognized, hence undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality compromise bone strength causing fractures in COPD. In COPD patients, various general clinical risk factors for osteoporosis are present including smoking, older age, low body weight, and physical inactivity. In addition, disease-related risk factors such as decreased pulmonary function, inflammation, glucocorticoid use and vitamin D deficiency/insufficiency have been linked to the development of osteoporosis in COPD. Increased awareness of osteoporosis in COPD, especially that of high prevalence of vertebral fractures is called upon among general physicians as well as pulmonologists. Routine screening for osteoporosis and risk assessment of fractures will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage. Timely prevention of developing osteoporosis together with appropriate treatment of established osteoporosis may improve QOL and ADL of the COPD patients, preserve their lung function and eventually result in better prognosis in these patients.

  6. Endothelial Dysfunction in Chronic Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Curtis M. Steyers

    2014-06-01

    Full Text Available Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD. As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α, reactive oxygen species, oxidized LDL (low density lipoprotein, autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population.

  7. 28 CFR 79.67 - Proof of chronic renal disease.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of chronic renal disease. 79.67... renal disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... claimant. A conclusion that a claimant developed chronic renal disease must be supported by...

  8. Myocardial Ischemia Assessment in Chronic Kidney Disease: Challenges and Pitfalls

    OpenAIRE

    Susie Fei Cen Parnham; Gleadle, Jonathan M.; De Pasquale, Carmine G; Selvanayagam, Joseph B

    2014-01-01

    Coronary artery disease is the leading cause of mortality and morbidity in the chronic kidney disease population and often presents with atypical symptoms. Current diagnostic investigations of myocardial ischemia in chronic kidney disease lack sensitivity and specificity or may have adverse effects. We present a case vignette and explore the challenges of diagnostic myocardial stress investigation in patients with chronic kidney disease.

  9. Pregnancy in chronic kidney disease.

    Science.gov (United States)

    Vellanki, Kavitha

    2013-05-01

    Despite vast improvements in fetal outcomes, pregnancy in women with CKD is fraught with hazards; worsening of renal function and complications like preeclampsia and premature delivery are common. To date, there is no accurate formula to calculate glomerular filtration rate (GFR). Also, whether the current CKD classification is better than the older classification at predicting outcomes in pregnant women with CKD is unknown. Women with an estimated GFR ≥1.4 mg/dL are at increased risk of progressive worsening of renal function regardless of the cause of the underlying kidney disease. Preeclampsia is difficult to diagnose in pregnant women with underlying CKD, and serum markers such as soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PIGF) may lead the way for definitive diagnosis. New-onset lupus or lupus flare is an indication for kidney biopsy during pregnancy; cyclosporine is safe and is the most effective agent that can be used during pregnancy. Women with adult polycystic kidney disease are at increased risk of hypertension and preeclampsia during pregnancy, as well as hepatic cysts later in life, the latter occurring with multiple pregnancies. Strict blood pressure control is important in pregnant women with diabetic nephropathy. A multidisciplinary team that includes nephrologists and obstetricians who deal with high-risk pregnancies should be involved in the care of pregnant women with CKD for successful pregnancy outcomes. PMID:23928386

  10. Renal imaging in children with chronic kidney disease

    OpenAIRE

    Wiwit Rahmawati; Heru Muryawan; Farah Prabowo

    2013-01-01

    Background Chronic kidney failure is a cause of death in children. Diagnosing chronic kidney disease is often made by clinical manifestations, laboratory findings and ultrasonography or other imaging tests. Early detection of chronic kidney disease is needed for education and management of the disease. Objective To describe renal imaging findings and mortality in children with chronic kidney disease. Methods This was a cross-sectional study on children with kidney diseases who were in...

  11. Psychosocial interventions for patients with chronic disease

    Directory of Open Access Journals (Sweden)

    Deter Hans-Christian

    2012-01-01

    Full Text Available Abstract Treatment of patients with chronic diseases will be one of the main challenges of medicine in the future. This paper presents an overview of different origins, mechanism, and symptoms necessary for understanding new and different interventions that include a psychosomatic view. In a psychosomatic therapeutic intervention there are very different targets, such as psychological symptoms, personality traits, attitudes toward disease and life, risk behaviour, and social isolation and as biological targets the change of autonomic imbalance and of the effects of the psycho-endocrinological or psycho-immunological stress responses. And there are also different psychosomatic measures that influence the individual biological, psychological and sociological targets. There is a need to give different answer to different questions in the field of psychosomatic and behavioral medicine. Comparative effectiveness research is an important strategy for solving some methodological issues. What is the target of treatment for different diseases: Symptom reduction, healing, or limiting progression to the worst case - the death of patients. We know that, the patient-physician relationship is important for every medical/therapeutic action for patients with chronic diseases. This volume of BioPsychoSocial Medicine will present four different psychosomatic treatment studies from the clinical field in the sense of phase 2 studies: Reports of patients with obesity, anorexia nervosa, chronic somatoform pain and coronary artery disease were presented

  12. Alcoholic Beverage Consumption and Chronic Diseases.

    Science.gov (United States)

    Zhou, Yue; Zheng, Jie; Li, Sha; Zhou, Tong; Zhang, Pei; Li, Hua-Bin

    2016-01-01

    Epidemiological and experimental studies have consistently linked alcoholic beverage consumption with the development of several chronic disorders, such as cancer, cardiovascular diseases, diabetes mellitus and obesity. The impact of drinking is usually dose-dependent, and light to moderate drinking tends to lower risks of certain diseases, while heavy drinking tends to increase the risks. Besides, other factors such as drinking frequency, genetic susceptibility, smoking, diet, and hormone status can modify the association. The amount of ethanol in alcoholic beverages is the determining factor in most cases, and beverage types could also make an influence. This review summarizes recent studies on alcoholic beverage consumption and several chronic diseases, trying to assess the effects of different drinking patterns, beverage types, interaction with other risk factors, and provide mechanistic explanations. PMID:27231920

  13. Alcoholic Beverage Consumption and Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Yue Zhou

    2016-05-01

    Full Text Available Epidemiological and experimental studies have consistently linked alcoholic beverage consumption with the development of several chronic disorders, such as cancer, cardiovascular diseases, diabetes mellitus and obesity. The impact of drinking is usually dose-dependent, and light to moderate drinking tends to lower risks of certain diseases, while heavy drinking tends to increase the risks. Besides, other factors such as drinking frequency, genetic susceptibility, smoking, diet, and hormone status can modify the association. The amount of ethanol in alcoholic beverages is the determining factor in most cases, and beverage types could also make an influence. This review summarizes recent studies on alcoholic beverage consumption and several chronic diseases, trying to assess the effects of different drinking patterns, beverage types, interaction with other risk factors, and provide mechanistic explanations.

  14. Arterial hypertension and chronic liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, S

    2005-01-01

    , calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during......This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic...... the development of chronic liver disease, and arterial hypertension is rarely manifested in patients with cirrhosis, even in those with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial...

  15. Alcoholic Beverage Consumption and Chronic Diseases

    Science.gov (United States)

    Zhou, Yue; Zheng, Jie; Li, Sha; Zhou, Tong; Zhang, Pei; Li, Hua-Bin

    2016-01-01

    Epidemiological and experimental studies have consistently linked alcoholic beverage consumption with the development of several chronic disorders, such as cancer, cardiovascular diseases, diabetes mellitus and obesity. The impact of drinking is usually dose-dependent, and light to moderate drinking tends to lower risks of certain diseases, while heavy drinking tends to increase the risks. Besides, other factors such as drinking frequency, genetic susceptibility, smoking, diet, and hormone status can modify the association. The amount of ethanol in alcoholic beverages is the determining factor in most cases, and beverage types could also make an influence. This review summarizes recent studies on alcoholic beverage consumption and several chronic diseases, trying to assess the effects of different drinking patterns, beverage types, interaction with other risk factors, and provide mechanistic explanations. PMID:27231920

  16. Neurohumoral fluid regulation in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    1998-01-01

    Impaired homeostasis of the blood volume, with increased fluid and sodium retention, is a prevailing element in the deranged systemic and splanchnic haemodynamics in patients with liver disease. In this review, some basic elements of the circulatory changes that take place and of neurohumoral fluid...... regulation are outlined in order to provide an update of recent investigations on the neuroendocrine compensation of circulatory and volume dysfunction in chronic liver disease. The underlying pathophysiology is a systemic vasodilatation in which newly described potent vasoactive substances such as nitric...... and lungs. It is still an enigma why patients with chronic liver disease are at the same time overloaded and functional hypovolaemic with a hyperdynamic, hyporeactive circulation. Further research is needed to find the solution to this apparent haemodynamic conflict concerning the abnormal neurohumoral...

  17. Arterial Stiffness and Chronic Kidney Disease

    OpenAIRE

    Garnier, Anne-Sophie; Briet, Marie

    2016-01-01

    Chronic kidney disease (CKD) is a major public health concern due to the high prevalence of associated cardiovascular (CV) disease. CV mortality is 10-30 times higher in end-stage renal disease patients than in the age-adjusted general population. The last 20 years have been marked by a huge effort in the characterization of the vascular remodeling process associated with CKD and its consequences on the renal, CV and general prognosis. By comparison with patients with normal renal function, w...

  18. Mediterranean dietary pattern and chronic diseases.

    Science.gov (United States)

    Panico, Salvatore; Mattiello, Amalia; Panico, Camilla; Chiodini, Paolo

    2014-01-01

    The study of the relationship between the Mediterranean way of eating and the occurrence of diseases typical of the economically developed countries has been considered the starting point of nutritional epidemiology. From the Seven Countries Study in the 1950s to the recent European EPIC collaboration, the evaluation of the components of diet-affecting chronic diseases such as cardiovascular disease and cancer has been crucially based on the analysis of foods and nutrients characterizing the Mediterranean dietary habits. This long research history has been marked by a consistency of data over time when either single nutrients/food groups or more complex dietary patterns have been analyzed: The Mediterranean way of eating is a protective tool from cardiovascular diseases and many cancers. Italy has been a natural point of observation, starting from cardiovascular disease in the mid-1950s and continuing with major cancers. In spite of unfavorable lifestyle changes in the Italian population mostly due to globalization of unhealthy habits (richer diet and lower levels of physical activity), those individuals still close to the Mediterranean style are significantly protected. The very recent Italian data derived from the observation of about 50,000 individuals, participating in the Italian cohorts of the EPIC study, confirm these findings and are consistent with results from other European populations and in some cases also from North American populations. Moreover, several dietary trials suggest that such a way of eating improves both the metabolic risk condition for chronic disease and the occurrence of those diseases. In conclusion, a way of eating inspired by a Mediterranean dietary pattern is not only based on evidence but is also a palatable style that has contributed to protection from the epidemic of chronic diseases. PMID:24114475

  19. Chronic Liver Disease and American Indians/Alaska Natives

    Science.gov (United States)

    ... Native > Chronic Liver Disease Chronic Liver Disease and American Indians/Alaska Natives Among American Indians and Alaska Natives, ... 54. 1 At a glance – Cancer Rates for American Indian/Alaska Natives (2008-2012) Cancer Incidence Rates per ...

  20. Interleukin-22: a likely target for treatment of autoimmune diseases

    Science.gov (United States)

    Yang, Xuyan; Zheng, Song Guo

    2014-01-01

    Interleukin -22 (IL-22) is a member of IL-10 family cytokines that is produced by many different types of lymphocytes including both those of the innate and adaptive immune system. This includes activated T cells, most notably Th17 and Th22 cells, and NK cells, γδ T cells, LTi cells and LTi-like cells. IL-22 mediates its effects via the IL-22-IL-22R complex and subsequent Janus Kinase-signal transduces and activators transcription (JAK-STAT) signaling pathway. Recently accumulated evidence has indicated that IL-22 also plays an important role in the pathogenesis of many autoimmune diseases. In this review, we discuss the recent findings and advancement of the role for IL-22 in several autoimmune diseases, such as psoriasis, rheumatoid arthritis (RA), hepatitis, graft versus host disease (GHVD) and allergic diseases, implicating that target IL-22 may have a therapeutic potential in those autoimmune diseases. PMID:24418299

  1. Sleep disorders and chronic kidney disease.

    Science.gov (United States)

    Maung, Stephanie C; El Sara, Ammar; Chapman, Cherylle; Cohen, Danielle; Cukor, Daniel

    2016-05-01

    Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease (CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD. PMID:27152260

  2. Lactate metabolism in chronic liver disease

    DEFF Research Database (Denmark)

    Jeppesen, Johanne B; Mortensen, Christian; Bendtsen, Flemming;

    2013-01-01

    Background. In the healthy liver there is a splanchnic net-uptake of lactate caused by gluconeogenesis. It has previously been shown that patients with acute liver failure in contrast have a splanchnic release of lactate caused by a combination of accelerated glycolysis in the splanchnic region...... and a reduction in hepatic gluconeogenesis. Aims. The aims of the present study were to investigate lactate metabolism and kinetics in patients with chronic liver disease compared with a control group with normal liver function. Methods. A total of 142 patients with chronic liver disease and 14 healthy controls...... underwent a liver vein catheterization. Blood samples from the femoral artery and the hepatic and renal veins were simultaneously collected before and after stimulation with galactose. Results. The fasting lactate levels, both in the hepatic vein and in the femoral artery, were higher in the patients than...

  3. Direct renin inhibition in chronic kidney disease

    DEFF Research Database (Denmark)

    Persson, Frederik; Rossing, Peter; Parving, Hans-Henrik

    2013-01-01

    that renin inhibition could hold potential for improved treatment in patients with chronic kidney disease, with diabetic nephropathy as an obvious group of patients to investigate, as the activity of the renin-angiotensin-aldosterone system is enhanced in these patients and as there is an unmet need....... In addition, combination treatment seemed safe and effective also in patients with impaired kidney function. These initial findings formed the basis for the design of a large morbidity and mortality trial investigating aliskiren as add-on to standard treatment. The study has just concluded, but was terminated...... early as a beneficial effect was unlikely and there was an increased frequency of side effects. Also in non-diabetic kidney disease a few intervention studies have been carried out, but there is no ongoing hard outcome study. In this review we provide the current evidence for renin inhibition in chronic...

  4. 28 CFR 79.57 - Proof of chronic renal disease.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of chronic renal disease. 79.57... EXPOSURE COMPENSATION ACT Eligibility Criteria for Claims by Uranium Millers § 79.57 Proof of chronic renal disease. (a) In determining whether a claimant developed chronic renal disease following...

  5. Netherlands : employment opportunities for people with chronic diseases

    NARCIS (Netherlands)

    Hooftman, W.; Houtman, I.L.D.

    2014-01-01

    There is no clear national definition of a chronic disease in a work situation in the Netherlands. Questionnaire data shows that between 25% and 30% of all workers are affected by a chronic disease. Worker with a chronic disease have slightly different working conditions as compared to workers witho

  6. Chronic Kidney Disease: What Does It Mean for Me?

    Science.gov (United States)

    ... our online catalog. Alternate Language URL Españ​ol Chronic Kidney Disease (CKD) Basics Page Content Chronic Kidney Disease: The ... and My Lifestyle CKD: Tracking My Test Results Chronic Kidney Disease: The Basics You've been told that you ...

  7. Diaphragm Dysfunction in Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Ottenheijm, Coen A. C.; Heunks, Leo M.A.; Sieck, Gary C.; Zhan, Wen-Zhi; Jansen, Suzanne M.; Degens, Hans; de Boo, Theo; Dekhuijzen, P.N Richard

    2005-01-01

    Rationale: Hypercapnic respiratory failure because of inspiratory muscle weakness is the most important cause of death in chronic obstructive pulmonary disease (COPD). However, the pathophysiology of failure of the diaphragm to generate force in COPD is in part unclear. Objectives: The present study investigated contractile function and myosin heavy chain content of diaphragm muscle single fibers from patients with COPD. Methods: Skinned muscle fibers were isolated from muscle biopsies from t...

  8. Clinical Scenarios in Chronic Kidney Disease: Cystic Renal Diseases.

    Science.gov (United States)

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Cysts are frequently found in chronic kidney disease (CKD) and they have a different prognostic significance depending on the clinical context. Simple solitary parenchymal cysts and peripelvic cysts are very common and they have no clinical significance. At US, simple cyst appears as a round anechoic pouch with regular and thin profiles. On the other hand, hereditary polycystic disease is a frequent cause of CKD in children and adults. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are the best known cystic hereditary diseases. ADPKD and ARPKD show a diffused cystic degeneration with cysts of different diameters derived from tubular epithelium. Medullary cystic disease may be associated with tubular defects, acidosis and lithiasis and can lead to CKD. Acquired cystic kidney disease, finally, is secondary to progressive structural end-stage kidney remodelling and may be associated with renal cell carcinoma. PMID:27169740

  9. Chronic Diseases among Older Cancer Survivors

    Directory of Open Access Journals (Sweden)

    Laura Deckx

    2012-01-01

    Full Text Available Objective. To compare the occurrence of pre-existing and subsequent comorbidity among older cancer patients (≥60 years with older non-cancer patients. Material and Methods. Each cancer patient (n=3835, mean age 72 was matched with four non-cancer patients in terms of age, sex, and practice. The occurrence of chronic diseases was assessed cross-sectionally (lifetime prevalence at time of diagnosis and longitudinally (incidence after diagnosis for all cancer patients and for breast, prostate, and colorectal cancer patients separately. Cancer and non-cancer patients were compared using logistic and Cox regression analysis. Results. The occurrence of the most common pre-existing and incident chronic diseases was largely similar in cancer and non-cancer patients, except for pre-existing COPD (OR 1.21, 95% CI 1.06–1.37 and subsequent venous thrombosis in the first two years after cancer diagnosis (HR 4.20, 95% CI 2.74–6.44, which were significantly more frequent (P<0.01 among older cancer compared to non-cancer patients. Conclusion. The frequency of multimorbidity in older cancer patients is high. However, apart from COPD and venous thrombosis, the incidence of chronic diseases in older cancer patients is similar compared to non-cancer patients of the same age, sex, and practice.

  10. Chronic obstructive pulmonary disease and genetics

    DEFF Research Database (Denmark)

    Ingebrigtsen, T.; Thomsen, S.F.; Vestbo, J.;

    2008-01-01

    Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and is associated with an inflammatory response of the lungs primarily caused by cigarette smoking. Cigarette smoking is by far the most important environmental risk factor for COPD, but less than half of all heavy...... smokers develop COPD. This indicates a genetic contribution to the individual disease susceptibility. Although many genes have been examined, the puzzle of COPD genetics seems still largely unsolved. It is therefore important to measure phenotypes and to perform genome-wide scans of COPD patients in order...

  11. Ivabradine, heart failure and chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Luca Di Lullo

    2015-12-01

    Full Text Available The incidence and prevalence of congestive heart failure are actually increasing worldwide, especially in Western countries. In Europe and the United States, congestive heart failure represents a disabling clinical disease, accountable for increased hospitalization and health care costs. European guidelines have underlined the importance of pharmacological treatment to improve both patients’ outcomes and quality of life. The latest clinical trials to evaluate ivabradine’s efficacy have underlined its usefulness as a stand-alone medication and in combination with conventional congestive heart failure therapy, including in chronic kidney disease patients.

  12. Biomarkers in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Sin, Don D; Vestbo, Jørgen

    2009-01-01

    Currently, with exception of lung function tests, there are no well validated biomarkers or surrogate endpoints that can be used to establish efficacy of novel drugs for chronic obstructive pulmonary disease (COPD). However, the lung function test is not an ideal surrogate for short-term drug...... trials because it (1) does not provide information regarding disease activity or the underlying pathologic process, (2) cannot separate the various phenotypes of COPD, (3) is not specific for COPD, and (4) is relatively unresponsive to known therapies that prolong survival. Accordingly, there are large...

  13. Chronic liver disease in Aboriginal North Americans

    Institute of Scientific and Technical Information of China (English)

    John D Scott; Naomi Garland

    2008-01-01

    A structured literature review was performed to detail the frequency and etiology of chronic liver disease (CLD) in Aboriginal North Americans. CLD affects Aboriginal North Americans disproportionately and is now one of the most common causes of death.Alcoholic liver disease is the leading etiology of CLD,but viral hepatitis, particularly hepatitis C, is an important and growing cause of CLD. High rates of autoimmune hepatitis and primary biliary cirrhosis (PBC) are reported in regions of coastal British Columbia and southeastern Alaska. Non-alcoholic liver disease is a common, but understudied, cause of CLD.Future research should monitor the incidence and etiology of CLD and should be geographically inclusive.In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholicfatty liver disease (NAFLD) in this population.

  14. Vitamin D deficiency in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Paula; Iruzubieta; lvaro; Terán; Javier; Crespo; Emilio; Fábrega

    2014-01-01

    Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.

  15. Role of cannabinoids in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Anna Parfieniuk; Robert Flisiak

    2008-01-01

    Cannabinoids are a group of compounds acting primarily via CB1 and CB2 receptors. The expression of cannabinoid receptors in normal liver is low or absent. However, many reports have proven up-regulation of the expression of CB1 and CB2 receptors in hepatic myofibroblasts and vascular endothelial cells, as well as increased concentration of endocannabinoids in liver in the course of chronic progressive liver diseases. It has been shown that CB1 receptor signalling exerts profibrogenic and proinflammatory effects in liver tissue, primarily due to the stimulation of hepatic stellate cells, whereas the activation of CB2 receptors inhibits or even reverses liver fibrogenesis. Similarly, CB1 receptor stimulation contributes to progression of liver steatosis. In end-stage liver disease, the endocannabi-noid system has been shown to contribute to hepatic encephalopathy and vascular effects, such as portal hypertension, splanchnic vasodilatation, relative pe-ripheral hypotension and probably cirrhotic cardiomy-opathy. So far, available evidence is based on cellular cultures or animal models. Clinical data on the effects of cannabinoids in chronic liver diseases are limited. However, recent studies have shown the contribution of cannabis smoking to the progression of liver fibrosis and steatosis. Moreover, controlling CB1 or CB2 signal-ling appears to be an attractive target in managing liver diseases.

  16. Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?

    Directory of Open Access Journals (Sweden)

    Yan He

    2015-05-01

    Full Text Available It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

  17. Methylotroph Infections and Chronic Granulomatous Disease.

    Science.gov (United States)

    Falcone, E Liana; Petts, Jennifer R; Fasano, Mary Beth; Ford, Bradley; Nauseef, William M; Neves, João Farela; Simões, Maria João; Tierce, Millard L; de la Morena, M Teresa; Greenberg, David E; Zerbe, Christa S; Zelazny, Adrian M; Holland, Steven M

    2016-03-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte-derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease-causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis.

  18. [Pulmonary obstructive chronic disease and physical exercise].

    Science.gov (United States)

    António, Carla; Gonçalves, Ana Paula; Tavares, Alcina

    2010-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is a disease that can be prevented and treated, with a pulmonary component and with significant systemic effects that contribute to the severity of clinical manifestations. COPD causes a number of changes, including those which lead to exercise tolerance limitation and to a progressive deterioration of life quality of the patients. Respiratory rehabilitation (RR) represents a key part of the treatment. The benefits of RR are independent of sex, age and disease severity. At the end of the program, the patient should have acquired a life style as independent and healthy as possible. With this article the authors intend to review the benefits of physical exercise in rehabilitation of patients with COPD and the different types of training used in the respiratory rehabilitation program established for each patient. PMID:20700562

  19. Chronic kidney disease: considerations for nutrition interventions.

    Science.gov (United States)

    Steiber, Alison L

    2014-05-01

    Chronic kidney disease (CKD) is highly prevalent and has major health consequences for patients. Caring for patients with CKD requires knowledge of the food supply, renal pathophysiology, and nutrition-related medications used to work synergistically with diet to control the signs and symptoms of the disease. The nutrition care process and International Dietetic and Nutrition Terminology allow for systematic, holistic, quality care of patients with this complex, progressive disease. Nutrition interventions must be designed with the individual patients needs in mind while prioritizing factors with the largest negative impact on health outcomes and mortality risk. New areas of nutrition treatment are emerging that involve a greater focus on micronutrient needs, the microbiome, and vegetarian-style diets. These interventions may improve outcomes by decreasing inflammation, improving energy and protein delivery, and lowering phosphorus, electrolytes, and fluid retention.

  20. Langerhans cells and their role in oral mucosal diseases.

    Science.gov (United States)

    Upadhyay, Juhi; Upadhyay, Ram B; Agrawal, Pankaj; Jaitley, Shweta; Shekhar, Rhitu

    2013-09-01

    Dendritic cells are arguably the most potent antigen-presenting cells and may be the only cells capable of initiating the adaptive immune response. The epithelial residents of dendritic cells are Langerhans cells, which serve as the "sentinels" of the mucosa, altering the immune system not only to pathogen entry but also of tolerance to self antigen and commensal microbes. Oral mucosal Langerhans cells are capable of engaging and internalizing a wide variety of pathogens and have been found responsive to nickel in patients with nickel allergies, oral Candida species, oral lichen planus, lichenoid drug eruptions, graft versus host diseases, periodontal diseases median rhomboid glossitis, human immunodeficiency virus infection, hairy leukoplakia of the tongue, and oral squamous cell carcinoma. Review focuses on the role of antigen-presenting cells in particular Langerhans cells to better understand the mechanisms underlying immune responses. In this review, comprehensive detail about mucosal diseases has been compiled using the PubMed database and through textbooks. PMID:24251267

  1. Natural histories of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Rennard, Stephen I; Vestbo, Jørgen

    2008-01-01

    English men over 8 years, was used to construct a proposed life-long natural history. Although this is a classic study that has greatly advanced understanding of COPD, it has a number of limitations. Its duration is relatively short compared with the duration of COPD, so it is more cross-sectional than......Concepts relating to the natural history of chronic obstructive pulmonary disease (COPD) arise most importantly from the classic study of Fletcher and colleagues (The Natural History of Chronic Bronchitis and Emphysema, Oxford University Press, New York, 1976). This study, which evaluated working...... longitudinal. It was unable to distinguish among varied "natural histories." It assessed primarily the FEV(1), and the natural history of other features of COPD is largely undescribed. With advances in understanding the clinical features of COPD and with the development of evaluating new tools to assess...

  2. Related and unrelated nonmyeloablative hematopoietic stem cell transplantation for malignant diseases.

    Science.gov (United States)

    Georges, George E; Maris, Michael; Sandmaier, Brenda M; Malone, David G; Feinstein, Lyle; Niederweiser, Dietger; Shizuru, Judith A; McSweeney, Peter A; Chauncey, Thomas R; Agura, Edward; Little, Marie-Trse; Sahebi, Firoozeh; Hegenbart, Ute; Pulsipher, Michael A; Bruno, Benedetto; Forman, Stephen; Woolfrey, Ann E; Radich, Jerald P; Blume, Karl G; Storb, Rainer

    2002-08-01

    Patients with advanced hematological malignancies ineligible for conventional myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) due to advanced age or medical contraindications were enrolled in multi-center study to investigate the safety and efficacy of nonmyeloablative HSCT using a 2 Gy total body irradi ation (TBI)-based regimen. A total of 192 patients (median age 55) were treated with HLA-matched sibling peripheral blood stem cell (PBSC) grafts, and 63 patients (median age 53) received a 10 of 10 HLA-antigen matched unrelated donor (URD) HSCT (PBSC graft, n = 48; marrow graft, n = 15). Diagnoses included multiple myeloma (n = 61), myelodysplastic syndrome (n = 55), chronic myeloid leukemia (n = 31), non-Hodgkin lymphoma (n = 31), acute myeloid leukemia (n = 28), chronic lymphocytic leukemia (n = 24), Hodgkin Disease (n = 14). The conditioning regimen was fludarabine 30 mg/m2/d x 3 days and 2 Gy TBI. Ninety-five related HSCT patients received 2 Gy TBI without fludarabine. Postgrafting immunosuppression was combined mycophenolate mofetil an cyclosporine. Transplants were well tolerated with a median of 0 days of hospitalization in the first 60 days for eligible patients. For related HSCT recipients, median follow-up was 289 (100-1,188) days. Nonfatal graft rejection occurred in 6.8%. Of those with sustained engraftment, graft-versus-host disease (GVHD) occurred in 49% (33% grade II, 11% grade III, 5% grade IV). Day-100 non-relapse mortality was 6%. Overall, 59% (114/192) of patients were alive. The relapse/disease progression mortality was 18%, and non-relapse mortality was 22%. The projecte 2-year survival and progression-free survival were 50% and 40%. For the URD HSCT recipients, median follow-up was 190 (100-468) days. Graft rejection occurred in 27% (17/63) of patients, mostly in recipients of marrow grafts (9/15). Acute GVHD occurred in 63% (50% grade II, 13% grade III) of 46 engrafted patients. Chronic GVHD requiring therapy occurred

  3. Screening for chronic kidney disease : Where does Europe go?

    NARCIS (Netherlands)

    de Jong, Paul E.; van der Velde, Marije; Gansevoort, Ron T.; Zoccali, Carmine

    2008-01-01

    This review discusses various screening approaches for chronic kidney disease that are used in Europe. The criterion for defining chronic kidney disease in the various programs differs but is frequently limited to estimated glomerular filtration rate, thus offering only data on chronic kidney diseas

  4. Hypertension and chronic kidney disease in Turkey.

    Science.gov (United States)

    Sengul, Sule; Erdem, Yunus; Batuman, Vecihi; Erturk, Sehsuvar

    2013-12-01

    Worldwide, both hypertension and chronic kidney disease are major public health problems, due to their epidemic proportions and their association with high cardiovascular mortality. In 2003, the first Prevalence, awareness, treatment, and control of hypertension in Turkey (the PatenT) study was conducted in a nationally representative population (n=4910) by the Turkish Society of Hypertension and Renal Diseases, and showed that overall age- and sex-adjusted prevalence of hypertension in Turkey was 31.8%. The PatenT study also reported that overall awareness (40.7%), treatment (31.1%), and control rates (8.1%) of hypertension were strikingly low. Only 20.7% of the patients who were aware of their hypertension and receiving treatment had their blood pressure controlled to diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome were reported as 32.7%, 12.7%, 76.3%, 20.1%, and 31.3%, respectively. The prevalence and awareness of hypertension in CREDIT population was 32.7% and 48.6%, respectively. According to the data obtained from national surveys, the prevalence of hypertension and chronic kidney disease in Turkey is alarmingly high. To improve prevention, early diagnosis, and treatment of these major public health problems, appropriate health strategies should be implemented by the government, together with medical societies, non-governmental organizations, industry, health-care providers, and academia. PMID:25019009

  5. Genetic Considerations in Pediatric Chronic Kidney Disease.

    Science.gov (United States)

    Harshman, Lyndsay A; Zepeda-Orozco, Diana

    2016-03-01

    Chronic kidney disease (CKD) in children is an irreversible process that, in some cases, may lead to end-stage renal disease. The majority of children with CKD have a congenital disorder of the kidney or urological tract arising from birth. There is strong evidence for both a genetic and epigenetic component to progression of CKD. Utilization of gene-mapping strategies, ranging from genome-wide association studies to single-nucleotide polymorphism analysis, serves to identify potential genetic variants that may lend to disease variation. Genome-wide association studies evaluating population-based data have identified different loci associated with CKD progression. Analysis of single-nucleotide polymorphisms on an individual level suggests that secondary systemic sequelae of CKD are closely related to dysfunction of the cardiovascular-inflammatory axis and may lead to advanced cardiovascular disease through abnormal vascular calcification and activation of the renin-angiotensin system. Similarly, genetic variants affecting cytokine control, fibrosis, and parenchymal development may modulate CKD through development and acceleration of renal interstitial fibrosis. Epigenetic studies evaluate modification of the genome through DNA methylation, histone modification, or RNA interference, which may be directly influenced by external or environmental factors directing genomic expression. Lastly, improved understanding of the genetic and epigenetic contribution to CKD progression may allow providers to identify a population at accelerated risk for disease progression and apply novel therapies targeted at the genetic mechanism of disease. PMID:27617141

  6. Myocardial Ischemia Assessment in Chronic Kidney Disease: Challenges and Pitfalls

    Directory of Open Access Journals (Sweden)

    Susie Fei Cen Parnham

    2014-12-01

    Full Text Available Coronary artery disease is the leading cause of mortality and morbidity in the chronic kidney disease population and often presents with atypical symptoms. Current diagnostic investigations of myocardial ischemia in chronic kidney disease lack sensitivity and specificity or may have adverse effects. We present a case vignette and explore the challenges of diagnostic myocardial stress investigation in patients with chronic kidney disease.

  7. Analysis of electrocardiogram in chronic obstructive pulmonary disease patients

    OpenAIRE

    Lazović Biljana; Zlatković-Švenda Mirjana; Mazić Sanja; Stajić Zoran; Đelić Marina

    2013-01-01

    Introduction. Chronic obstructive pulmonary disease is the fourth leading cause of mortality worldwide. It is defined as a persistent airflow limitation usually progressive and not fully reversible to treatment. The diagnosis of chronic obstructive pulmonary disease and severity of disease is confirmed by spirometry. Chronic obstructive pulmonary disease produces electrical changes in the heart which shows characteristic electrocardiogram pattern. The aim of this study was to observe an...

  8. Pathophysiology and treatment of inflammatory anorexia in chronic disease

    OpenAIRE

    Braun, Theodore P.; Marks, Daniel L.

    2010-01-01

    Decreased appetite and involuntary weight loss are common occurrences in chronic disease and have a negative impact on both quality of life and eventual mortality. Weight loss in chronic disease comes from both fat and lean mass, and is known as cachexia. Both alterations in appetite and body weight loss occur in a wide variety of diseases, including cancer, heart failure, renal failure, chronic obstructive pulmonary disease and HIV. An increase in circulating inflammatory cytokines has been ...

  9. Vitamin K status in chronic kidney disease.

    Science.gov (United States)

    McCabe, Kristin M; Adams, Michael A; Holden, Rachel M

    2013-11-07

    The purpose of this review is to summarize the research to date on vitamin K status in chronic kidney disease (CKD). This review includes a summary of the data available on vitamin K status in patients across the spectrum of CKD as well as the link between vitamin K deficiency in CKD and bone dynamics, including mineralization and demineralization, as well as ectopic mineralization. It also describes two current clinical trials that are underway evaluating vitamin K treatment in CKD patients. These data may inform future clinical practice in this population.

  10. Chronic obstructive pulmonary disease in women

    OpenAIRE

    Louis Laviolette; Yves Lacasse; Mariève Doucet; Miriam Lacasse; Karine Marquis; Didier Saey; Pierre Leblanc; François Maltais

    2007-01-01

    BACKGROUND: Little is known about the comparative impact of chronic obstructive pulmonary disease (COPD) between women and men and about women’s response to pulmonary rehabilitation.OBJECTIVES: To compare lung function, disability, mortality and response to pulmonary rehabilitation between women and men with COPD.METHODS: In the present retrospective study, 68 women (mean age 62.5±8.9 years) and 168 men (mean age 66.3±8.4 years) were evaluated by means of pulmonary function testing and an inc...

  11. Vitamin K Status in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Rachel M. Holden

    2013-11-01

    Full Text Available The purpose of this review is to summarize the research to date on vitamin K status in chronic kidney disease (CKD. This review includes a summary of the data available on vitamin K status in patients across the spectrum of CKD as well as the link between vitamin K deficiency in CKD and bone dynamics, including mineralization and demineralization, as well as ectopic mineralization. It also describes two current clinical trials that are underway evaluating vitamin K treatment in CKD patients. These data may inform future clinical practice in this population.

  12. Vascular cognitive impairments in chronic kidney disease

    OpenAIRE

    I. V. Rogova; Fomin, V. V.; I. V. Damulin; E. G. Minakova; O. Yu. Selivanova; Yu. A. Petleva

    2015-01-01

    Objective: to study the specific features of development of cognitive impairments (CIs), the role of traditional cardiovascular risk factors and renal failure-induced factors in patients with Stages I–IV chronic kidney disease (CKD) and to assess an association of CIs with the signs of vascular wall remodeling in them. Patients and methods. Fifty-one patients aged 53±10 years with CKD were examined. Among them, there were 20 patients with Stages I–II CKD: a glomerular filtration rate (GFR) of...

  13. [Prevention of Chronic Kidney Disease and strategies to counteract chronic diseases in Italy].

    Science.gov (United States)

    Mastrilli, Valeria; D'Elia, Roberto; Galeone, Daniela

    2016-01-01

    The Prevention of Chronic Kidney Disease (CKD) is placed in the more general context of prevention of major chronic Non Communicable Diseases (NCDs): cardiovascular diseases, diabetes, chronic lung diseases and tumors that are the main problem for public health worldwide. Any health policy strategy aimed to the prevention of NCDs has to provide knowledge of health and socioeconomic status of the population, to reduce the level of exposure to risk factors and to adapt health services to the request for assistance. To this purpose, population monitoring systems have been implemented in the last years. The NCDs share some risk factors that are related, in large part, to unhealthy individual behaviours: smoking, alcohol abuse, unhealthy diet and physical inactivity. NCDs prevention has to be understood as the set of all actions, sanitary and not, aiming to prevent or delay the onset of diseases or their complications. Preventive measures should, therefore, involve not only the health sector but also all the actors that can help to prevent that disease. As for the Prevention of CKD, the Ministry of Health has established a working table, which handled the Drafting of the "Position paper for the CKD", approved in the State-Regions Conference on august 8th 2014. The document draws a national strategy to combat this disease through primary prevention, early diagnosis and the establishment of diagnostic - therapeutic pathways (DTP). PMID:27545630

  14. ISCHEMIA in chronic kidney disease: improving the representation of patients with chronic kidney disease in cardiovascular trials.

    Science.gov (United States)

    Wyatt, Christina M; Shineski, Matthew; Chertow, Glenn M; Bangalore, Sripal

    2016-06-01

    Despite the high cardiovascular risk associated with chronic kidney disease, a recent systematic review confirmed that patients with kidney disease remain underrepresented in cardiovascular trials. Two ongoing trials are assessing the risk:benefit of aggressive evaluation and intervention for ischemic heart disease in patients with advanced chronic kidney disease.

  15. Therapeutic Potential of Mesenchymal Stem Cells for the Treatment of Airway Remodeling in Pulmonary Diseases.

    Science.gov (United States)

    Nejad-Moghaddam, Amir; Panahi, Yunes; Abdollahpour Alitappeh, Meghdad; Borna, Hojat; Shokrgozar, Mohammad Ali; Ghanei, Mostafa

    2015-12-01

    According to significant improvements in the tissue engineering field over the past several years, lung tissue cells have recently attracted more attention due to the high prevalence and diversity in related diseases. However, selection of an appropriate cell type, screening of suitable conditions for growth and proliferation, as well as subsequent implantation into the body to repair and regenerate damaged tissues are considered as important issues in this context. It should also be noted that most studies have been described in animal models, but not in humans. Because of the high regenerative capacity, predominant immunomodulatory feature, and inhibition of T-lymphocyte proliferation, mesenchymal stem cells (MSCs) may play an important role in the reconstruction of damaged tissues including bronchioles in pulmonary diseases. Interestingly, clinical trial studies demonstrated that MSCs have the significant potential to treat a wide variety of diseases including acute myocardial infarction (AMI), liver cirrhosis, crohn's disease, and graft-versus-host disease (GVHD). PMID:26725553

  16. Therapeutic Potential of Mesenchymal Stem Cells for the Treatment of Airway Remodeling in Pulmonary Diseases

    Directory of Open Access Journals (Sweden)

    Amir Nejad-Moghaddam

    2015-11-01

    Full Text Available According to significant improvements in the tissue engineering field over the past several years, lung tissue cells have recently attracted more attention due to the high prevalence and diversity in related diseases. However, selection of an appropriate cell type, screening of suitable conditions for growth and proliferation, as well as subsequent implantation into the body to repair and regenerate damaged tissues are considered as important issues in this context. It should also be noted that most studies have been described in animal models, but not in humans. Because of the high regenerative capacity, predominant immunomodulatory feature, and inhibition of T-lymphocyte proliferation, mesenchymal stem cells (MSCs may play an important role in the reconstruction of damaged tissues including bronchioles in pulmonary diseases. Interestingly, clinical trial studies demonstrated that MSCs have the significant potential to treat a wide variety of diseases including acute myocardial infarction (AMI, liver cirrhosis, crohn’s disease, and graft-versus-host disease (GVHD.

  17. Palifermin in Preventing Oral Mucositis Caused by Chemotherapy and/or Radiation Therapy in Young Patients Undergoing Stem Cell Transplant

    Science.gov (United States)

    2013-05-30

    Breast Cancer; Graft Versus Host Disease; Kidney Cancer; Leukemia; Lymphoma; Mucositis; Multiple Myeloma; Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

  18. Telomeres, NAFLD and Chronic Liver Disease.

    Science.gov (United States)

    Donati, Benedetta; Valenti, Luca

    2016-01-01

    Telomeres consist of repeat DNA sequences located at the terminal portion of chromosomes that shorten during mitosis, protecting the tips of chromosomes. During chronic degenerative conditions associated with high cell replication rate, progressive telomere attrition is accentuated, favoring senescence and genomic instability. Several lines of evidence suggest that this process is involved in liver disease progression: (a) telomere shortening and alterations in the expression of proteins protecting the telomere are associated with cirrhosis and hepatocellular carcinoma; (b) advanced liver damage is a feature of a spectrum of genetic diseases impairing telomere function, and inactivating germline mutations in the telomerase complex (including human Telomerase Reverse Transcriptase (hTERT) and human Telomerase RNA Component (hTERC)) are enriched in cirrhotic patients independently of the etiology; and (c) experimental models suggest that telomerase protects from liver fibrosis progression. Conversely, reactivation of telomerase occurs during hepatocarcinogenesis, allowing the immortalization of the neoplastic clone. The role of telomere attrition may be particularly relevant in the progression of nonalcoholic fatty liver, an emerging cause of advanced liver disease. Modulation of telomerase or shelterins may be exploited to prevent liver disease progression, and to define specific treatments for different stages of liver disease. PMID:26999107

  19. L'azacytidine prévient la maladie du greffon contre l'hôte de type chronique sclérodermique expérimentale

    OpenAIRE

    Fransolet, Gilles; Ehx, Grégory; Somja, Joan; Belle, Ludovic; Drion, Pierre; Humblet-Baron, Stéphanie; Beguin, Yves; Baron, Frédéric

    2015-01-01

    Introduction: Graft-versus-host disease (GVHD) remains one major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Following unmanipulated peripheral-blood stem cell transplantation, 60% of the patients experience chronic GVHD while approximately 15% of them develop a sclerodermic form of chronic GVHD characterized by multiple organ fibrosis and loss of skin elasticity. Regulatory T cells (Tregs) play a pivotal role in the pathology of chronic GVHD by inhibiting allor...

  20. Chronic obstructive pulmonary disease: an overview.

    Science.gov (United States)

    Duncan, Deborah

    As chronic obstructive pulmonary disease (COPD) is one of the major causes of worldwide mortality, it is important to prevent, diagnose and manage it. COPD creates a huge burden on the NHS and has a significant impact on patients. This is a problem with the increase in morbidity and mortality rates. In primary care there is a lack of knowledge, under-use of quality-assured spirometry and under-diagnosis in about half of all cases. To be able to effectively diagnose, assess and manage COPD, health professionals must understand the physiology and aetiology of the disease. COPD is similar to asthma in its presentation and physiology but management of the condition can differ. The authors therefore looked at the similarities between the two conditions and what tests one can use to make a diagnosis of COPD. PMID:27081728

  1. Achieving Salt Restriction in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Emma J. McMahon

    2012-01-01

    Full Text Available There is consistent evidence linking excessive dietary sodium intake to risk factors for cardiovascular disease and chronic kidney disease (CKD progression in CKD patients; however, additional research is needed. In research trials and clinical practice, implementing and monitoring sodium intake present significant challenges. Epidemiological studies have shown that sodium intake remains high, and intervention studies have reported varied success with participant adherence to a sodium-restricted diet. Examining barriers to sodium restriction, as well as factors that predict adherence to a low sodium diet, can aid researchers and clinicians in implementing a sodium-restricted diet. In this paper, we critically review methods for measuring sodium intake with a specific focus on CKD patients, appraise dietary adherence, and factors that have optimized sodium restriction in key research trials and discuss barriers to sodium restriction and factors that must be considered when recommending a sodium-restricted diet.

  2. [Chronic ischaemic heart disease in the elderly].

    Science.gov (United States)

    Martínez-Sellés, Manuel; Gómez Huelgas, Ricardo; Abu-Assi, Emad; Calderón, Alberto; Vidán, María Teresa

    2016-01-01

    It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging. PMID:27102136

  3. [Neurourological signs of chronic cerebral vascular diseases].

    Science.gov (United States)

    Shvarts, P G; Dutov, V V; Kadykov, A S; Shvedkov, V V; Popov, S V; Plotnikov, A N

    2013-01-01

    Disorders of urination, along with motor and cognitive disorders, are characteristic of different forms of chronic cerebral vascular diseases (CCVD). Irritation symptoms are more frequent in subcortical arteriosclerotic encephalopathy (SAE) and multi infarct hypertonic encephalopathy (MIHE). Overactive urine bladder syndrome (OUBS) caused by neurogenic detrusive hyperactivity manifests itself in frequent urination, nocturia and imperative enuresis and thus decreases quality of life and results in disability of patents with CCVD. At the same time, the character of symptoms points indirectly to the localization of lacunar infarction or the extent of severity of leukoareosis. It is the most frequent form of disorders of urination in the first years of disease that significantly aggravates its course and needs timed diagnosis and pharmacological treatment. Competitive antagonists of muscarinic receptors M2, M3 subtypes are the most effective drugs for treatment of OUBS comorbid to CCVD. PMID:23994932

  4. Tetracycline therapy for chronic Lyme disease.

    Science.gov (United States)

    Donta, S T

    1997-07-01

    Two hundred seventy-seven patients with chronic Lyme disease were treated with tetracycline for 1 to 11 months (mean, 4 months); the outcomes for these patients were generally good. Overall, 20% of the patients were cured; 70% of the patients' conditions improved, and treatment failed for 10% of the patients. Improvement frequently did not take place for several weeks; after 2 months of treatment, 33% of the patients' conditions were significantly improved (degree of improvement, 75%-100%), and after 3 months of treatment, 61% of the patients' conditions were significantly improved. Treatment outcomes for seronegative patients (20% of all patients) were similar to those for seropositive patients. Western immunoblotting showed reactions to one or more Borrelia burgdorferi-specific proteins for 65% of the patients for whom enzyme-linked immunosorbent assays were negative. Whereas age, sex, and prior erythema migrans were not correlated with better or worse treatment outcomes, a history of longer duration of symptoms or antibiotic treatment was associated with longer treatment times to achieve improvement and cure. These results support the use of longer courses of treatment in the management of patients with chronic Lyme disease. Controlled trials need to be conducted to validate these observations.

  5. Spiritual Needs of Patients with Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Harold G. Koenig

    2010-11-01

    Full Text Available For many patients confronted with chronic diseases, spirituality/religiosity is an important resource for coping. Patients often report unmet spiritual and existential needs, and spiritual support is also associated with better quality of life. Caring for spiritual, existential and psychosocial needs is not only relevant to patients at the end of their life but also to those suffering from long-term chronic illnesses. Spiritual needs may not always be associated with life satisfaction, but sometimes with anxiety, and can be interpreted as the patients’ longing for spiritual well-being. The needs for peace, health and social support are universal human needs and are of special importance to patients with long lasting courses of disease. The factor, Actively Giving, may be of particular importance because it can be interpreted as patients’ intention to leave the role of a `passive sufferer´ to become an active, self-actualizing, giving individual. One can identify four core dimensions of spiritual needs, i.e., Connection, Peace, Meaning/Purpose, and Transcendence, which can be attributed to underlying psychosocial, emotional, existential, and religious needs. The proposed model can provide a conceptual framework for further research and clinical practice. In fact, health care that addresses patients’ physical, emotional, social, existential and spiritual needs (referring to a bio-psychosocial-spiritual model of health care will contribute to patients’ improvement and recovery. Nevertheless, there are several barriers in the health care system that makes it difficult to adequately address these needs.

  6. Cardiovascular Disease and Chronic Inflammation in End Stage Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sofia Zyga

    2013-01-01

    Full Text Available Background: Chronic Kidney Disease (CKD is one of the most severe diseases worldwide. In patients affected by CKD, a progressive destruction of the nephrons is observed not only in structuralbut also in functional level. Atherosclerosis is a progressive disease of large and medium-sized arteries. It is characterized by the deposition of lipids and fibrous elements and is a common complication of the uremic syndrome because of the coexistence of a wide range of risk factors. High blood pressure, anaemia, insulin resistance, inflammation, high oxidative stress are some of the most common factors that cause cardiovascular disease and atherogenesis in patients suffering from End Stage Kidney Disease (ESRD. At the same time, the inflammatory process constitutes a common element in the apparition and development of CKD. A wide range of possible causes can justify the development of inflammation under uremic conditions. Such causes are oxidative stress, oxidation, coexistentpathological conditions as well as factors that are due to renal clearance techniques. Patients in ESRD and coronary disease usually show increased acute phase products. Pre-inflammatory cytokines, such as IL-6 and TNF-a, and acute phase reactants, such as CRP and fibrinogen, are closely related. The treatment of chronic inflammation in CKD is of high importance for the development ofthe disease as well as for the treatment of cardiovascular morbidity.Conclusions: The treatment factors focus on the use of renin-angiotensic system inhibitors, acetylsalicylic acid, statins and anti-oxidant treatment in order to prevent the action of inflammatorycytokines that have the ability to activate the mechanisms of inflammation.

  7. Nutrition for Early Chronic Kidney Disease in Adults

    Science.gov (United States)

    ... Disease Organizations​​ . (PDF, 345 KB)​​​​​ Alternate Language URL Nutrition for Early Chronic Kidney Disease in Adults Page ... choices? Points to Remember Clinical Trials Why is nutrition important for someone with early chronic kidney disease ( ...

  8. Obesity, hypertension, and chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Hall ME

    2014-02-01

    Full Text Available Michael E Hall,1,2 Jussara M do Carmo,2 Alexandre A da Silva,2 Luis A Juncos,1,2 Zhen Wang,2 John E Hall2 1Department of Medicine, 2Department of Physiology and Biophysics, Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, USA Abstract: Obesity is a major risk factor for essential hypertension, diabetes, and other comorbid conditions that contribute to development of chronic kidney disease. Obesity raises blood pressure by increasing renal tubular sodium reabsorption, impairing pressure natriuresis, and causing volume expansion via activation of the sympathetic nervous system and renin-angiotensin-aldosterone system and by physical compression of the kidneys, especially when there is increased visceral adiposity. Other factors such as inflammation, oxidative stress, and lipotoxicity may also contribute to obesity-mediated hypertension and renal dysfunction. Initially, obesity causes renal vasodilation and glomerular hyperfiltration, which act as compensatory mechanisms to maintain sodium balance despite increased tubular reabsorption. However, these compensations, along with increased arterial pressure and metabolic abnormalities, may ultimately lead to glomerular injury and initiate a slowly developing vicious cycle that exacerbates hypertension and worsens renal injury. Body weight reduction, via caloric restriction and increased physical activity, is an important first step for management of obesity, hypertension, and chronic kidney disease. However, this strategy may not be effective in producing long-term weight loss or in preventing cardiorenal and metabolic consequences in many obese patients. The majority of obese patients require medical therapy for obesity-associated hypertension, metabolic disorders, and renal disease, and morbidly obese patients may require surgical interventions to produce sustained weight loss. Keywords: visceral adiposity, type II diabetes, sodium reabsorption

  9. Chronic obstructive pulmonary disease and peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Gupta Prem

    2006-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death world-wide and a further increase in the prevalence as well as mortality of the disease is predicted for coming decades. There is now an increased appreciation for the need to build awareness regarding COPD and to help the thousands of people who suffer from this disease and die prematurely from COPD or its associated complication(s. Peripheral neuropathy in COPD has received scanty attention despite the fact that very often clinicians come across COPD patients having clinical features suggestive of peripheral neuropathy. Electrophysiological tests like nerve conduction studies are required to distinguish between axonal and demyelinating type of disorder that cannot be analyzed by clinical examination alone. However, various studies addressing peripheral neuropathy in COPD carried out so far have included patients with COPD having markedly varying baseline characteristics like severe hypoxemia, elderly patients, those with long duration of illness, etc. that are not uniform across the studies and make it difficult to interpret the results to a consistent conclusion. Almost one-third of COPD patients have clinical evidence of peripheral neuropathy and two-thirds have electrophysiological abnormalities. Some patients with no clinical indication of peripheral neuropathy do have electrophysiological deficit suggestive of peripheral neuropathy. The more frequent presentation consists of a polyneuropathy that is subclinical or with predominantly sensory signs, and the neurophysiological and pathological features of predominantly axonal neuropathy. The presumed etiopathogenic factors are multiple: chronic hypoxia, tobacco smoke, alcoholism, malnutrition and adverse effects of certain drugs.

  10. Current treatment in chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    李嘉惠

    2008-01-01

    Chronic obstructive pulmonary disease (COPD) is defined by fixed airflow limitation associated with an abnormal pulmonary and systemic inflammatory response of the lungs to cigarette smoke. COPD represents an increasing burden worldwide, reported to be the sixth leading cause of death in 1990 and the fourth in 2000. Discouragingly, it is projected to jump to third place by the year 2020.There is increasing evidence that COPD is a more complex systemic disease than an airway and lung disease. In particular, cachexia, skeletal muscle abnormalities, diabetes, coronary artery disease, heart failure, cancer and pulmonary vascular disease are the most common comorbidities. It is associated with a wide variety of systemic consequences, most notably systemic inflammation. Because COPD patients have in general ahigher cardiovascular risk than the average population, cardiovascular safety in a COPD medication is of critical importance.SINGH et al performed a systematic review and recta-analysis of 17 clinical trials enrolling 14 783 patients treated with inhaled anticholinergic drugs used for the treatment of COPD. Inhaled anticholinergics significantly increased the risk of cardiovascular death, MI, or stroke ( 1.8 % vs 1.2 % for control; RR, 1.58 (95 % CI,1.21 - 2.06); P < 0.001 ). However, UPLIIFT (Understanding the Potential Long-Term Impacts on Function with Tiotropium) , a large, 4-year, placebo controlled clinical trial with tiotropium in approximately 6 000 patients with COPD. The preliminary results of UPLIFT showed that there was no increased risk of stroke with tiotropium bromide compared to placebo.A meta-analysis is always considered less convincing than a large prospective trial designed to assess the outcome of interest. However, COPD is a systemic disease. COPD management needs to focus on four major areas: smoking cessation, pharmacologic therapy, exercise training, and pulmonary rehabilitation. Clinicians and patients should always carefully consider any

  11. Development and application of chronic disease risk prediction models.

    Science.gov (United States)

    Oh, Sun Min; Stefani, Katherine M; Kim, Hyeon Chang

    2014-07-01

    Currently, non-communicable chronic diseases are a major cause of morbidity and mortality worldwide, and a large proportion of chronic diseases are preventable through risk factor management. However, the prevention efficacy at the individual level is not yet satisfactory. Chronic disease prediction models have been developed to assist physicians and individuals in clinical decision-making. A chronic disease prediction model assesses multiple risk factors together and estimates an absolute disease risk for the individual. Accurate prediction of an individual's future risk for a certain disease enables the comparison of benefits and risks of treatment, the costs of alternative prevention strategies, and selection of the most efficient strategy for the individual. A large number of chronic disease prediction models, especially targeting cardiovascular diseases and cancers, have been suggested, and some of them have been adopted in the clinical practice guidelines and recommendations of many countries. Although few chronic disease prediction tools have been suggested in the Korean population, their clinical utility is not as high as expected. This article reviews methodologies that are commonly used for developing and evaluating a chronic disease prediction model and discusses the current status of chronic disease prediction in Korea.

  12. [New insights on hepcidin in anemia of chronic disease].

    Science.gov (United States)

    Wang, Feng-Dan; Zhou, Dao-Bin

    2009-12-01

    Anemia of chronic disease is normocytic and normochromic. One of the mechanisms is misbalance of iron metabolism. Hepcidin, a kind of protein secreted by liver is considered to be the hormone regulating iron metabolism. It binds to ferroportin and induces the latter one's internalization. Thus, iron transportation from iron storage cells to serum is reduced. Cytokines are elevated in chronic disease. They stimulate hepcidin expression in liver through JAK2/STAT3 pathway. As a result, iron absorption and reabsorption is blocked, which leads to the misbalance of iron metabolism in anemia of chronic disease. In this article, the hepcidin and its relation to iron metabolism and anemia in chronic disease are reviewed.

  13. Exploring metabolic dysfunction in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Slee Adrian D

    2012-04-01

    Full Text Available Abstract Impaired kidney function and chronic kidney disease (CKD leading to kidney failure and end-stage renal disease (ESRD is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabolic factors may play key roles in CKD development and pathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and −6, tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin, increased C-reactive protein, and perturbations in normal anabolic hormone responses with reduced growth hormone-insulin-like growth factor-1 axis activity. Others include hyperactivation of the renin-angiotensin aldosterone system (RAAS, with angiotensin II and aldosterone implicated in hypertension and the promotion of insulin resistance, and subsequent pharmacological blockade shown to improve blood pressure, metabolic control and offer reno-protective effects. Abnormal adipocytokine levels including leptin and adiponectin may further promote the insulin resistant, and proinflammatory state in CKD. Ghrelin may be also implicated and controversial studies suggest activities may be reduced in human CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin D status has also been associated with patient outcome and CVD risk and may indicate a role for supplementation. Glucocorticoid activities traditionally known for their involvement in the pathogenesis of a number of disease states are increased and may be implicated in CKD-associated hypertension, insulin resistance, diabetes risk and cachexia, both directly and indirectly through effects on other systems including activation of the mineralcorticoid

  14. Thyroid Disorders and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Mohamed Mohamedali

    2014-01-01

    Full Text Available Thyroid hormones play a very important role regulating metabolism, development, protein synthesis, and influencing other hormone functions. The two main hormones produced by the thyroid are triiodothyronine (T3 and thyroxine (T4. These hormones can also have significant impact on kidney disease so it is important to consider the physiological association of thyroid dysfunction in relation to chronic kidney disease (CKD. CKD has been known to affect the pituitary-thyroid axis and the peripheral metabolism of thyroid hormones. Low T3 levels are the most common laboratory finding followed by subclinical hypothyroidism in CKD patients. Hyperthyroidism is usually not associated with CKD but has been known to accelerate it. One of the most important links between thyroid disorders and CKD is uremia. Patients who are appropriately treated for thyroid disease have a less chance of developing renal dysfunction. Clinicians need to be very careful in treating patients with low T3 levels who also have an elevation in TSH, as this can lead to a negative nitrogen balance. Thus, clinicians should be well educated on the role of thyroid hormones in relation to CKD so that proper treatment can be delivered to the patient.

  15. Palliative care in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Lilly, Evan J; Senderovich, Helen

    2016-10-01

    Chronic obstructive pulmonary disease (COPD) is the only major worldwide cause of mortality that is currently increasing in prevalence. Furthermore, COPD is incurable, and the only therapy that has been shown to increase survival is oxygen therapy in selected patients. Compared to patients with cancer, patients with COPD experience similar levels of pain, breathlessness, fatigue, depression, and anxiety and have a worse quality of life but have comparatively little access to palliative care. When these patients do receive palliative care, they tend to be referred later than patients with cancer. Many disease, patient-, and provider-related factors contribute to this phenomenon, including COPD's unpredictable course, misperceptions of palliative care among patients and physicians, and lack of advance care planning discussions outside of crisis situations. A new paradigm for palliative care would introduce palliative treatments alongside, rather than at the exclusion of disease-modifying interventions. This integrated approach would circumvent the issue of difficult prognostication in COPD, as any patient would receive individualized palliative interventions from the time of diagnosis. These points will be covered in this review, which discusses the challenges in providing palliative care to COPD patients, the strategies to mitigate the challenges, management of common symptoms, and the evidence for integrated palliative care models as well as some suggestions for future development.

  16. Optimism's Explicative Role for Chronic Diseases.

    Science.gov (United States)

    Avvenuti, Giulia; Baiardini, Ilaria; Giardini, Anna

    2016-01-01

    The increasing interest about dispositional optimism's role in health status and its positive modulating effect on health outcomes has led to a remarkable scientific production in the last decade. To date lot is known for which diseases optimism is relevant, instead much less is known about how optimism interacts with other factors, both biological and psychological, in determining health status. The aim of this mini review is to explore the literature derived from clinical and experimental research assessing the associations between dispositional optimism and health status. Dispositional optimism can be considered as facet of personality that is cognitive in nature which holds the global expectation that the future will be plenty of good events. Optimists view desired goals as obtainable, so they often confront adversities in active manners resulting in perseverance and increased goal attainment. Only studies that explicitly included optimism and health outcomes, as measurable variables, and that reported a clear association between them have been reviewed. Cancer, cardiovascular disease, respiratory failure, and aging with multimorbidity were considered. Among the possible explicative hypotheses, two seem to best describe results: optimism may have a direct effect on the neuroendocrine system and on immune responses, and it may have an indirect effect on health outcomes by promoting protective health behaviors, adaptive coping strategies and enhancing positive mood. The research on optimism and health status has already shed light on important mechanisms regarding chronic diseases' management, however, further studies are needed to deepen the knowledge. PMID:26973582

  17. The pathology of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Hogg, James C; Timens, Wim

    2009-01-01

    The pathogenesis of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune response to the inhalation of toxic particles and gases. Although tobacco smoking is the primary cause of this inhalation injury, many other environmental and occupational exposures contribute to the pathology of COPD. The immune inflammatory changes associated with COPD are linked to a tissue-repair and -remodeling process that increases mucus production and causes emphysematous destruction of the gas-exchanging surface of the lung. The common form of emphysema observed in smokers begins in the respiratory bronchioles near the thickened and narrowed small bronchioles that become the major site of obstruction in COPD. The mechanism(s) that allow small airways to thicken in such close proximity to lung tissue undergoing emphysematous destruction remains a puzzle that needs to be solved. PMID:18954287

  18. Chronic Beryllium Disease Prevention Program Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S

    2012-03-29

    This document describes how Lawrence Livermore National Laboratory (LLNL) meets the requirements and management practices of federal regulation 10 CFR 850, 'Chronic Beryllium Disease Prevention Program (CBDPP).' This revision of the LLNL CBDPP incorporates clarification and editorial changes based on lessons learned from employee discussions, observations and reviews of Department of Energy (DOE) Complex and commercial industry beryllium (Be) safety programs. The information is used to strengthen beryllium safety practices at LLNL, particularly in the areas of: (1) Management of small parts and components; and (2) Communication of program status to employees. Future changes to LLNL beryllium activities and on-going operating experience will be incorporated into the program as described in Section S, 'Performance Feedback.'

  19. Growth hormone in chronic renal disease

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2012-01-01

    Full Text Available Severe growth retardation (below the third percentile for height is seen in up to one-third children with chronic kidney disease. It is thought to be multifactorial and despite optimal medical therapy most children are unable to reach their normal height. Under-nutrition, anemia, vitamin D deficiency with secondary hyperparathyroidism, metabolic acidosis, hyperphosphatemia, renal osteodystrophy; abnormalities in the growth hormone/insulin like growth factor system and sex steroids, all have been implicated in the pathogenesis of growth failure. Therapy includes optimization of nutritional and metabolic abnormalities. Failure to achieve adequate height despite 3-6 months of optimal medical measures mandates the use of recombinant GH (rGH therapy, which has shown to result in catch-up growth, anywhere from 2 cm to 10 cm with satisfactory liner, somatic and psychological development.

  20. Autonomic dysfunction in chronic liver disease

    Directory of Open Access Journals (Sweden)

    Frith J

    2011-08-01

    Full Text Available James Frith, Julia L NewtonNIHR Biomedical Research Centre in Ageing, Institute for Ageing and Health, Newcastle University, Newcastle, UKAbstract: It is becoming increasingly clear that quality of life (QOL is impaired in those with chronic liver disease (CLD. One of the most important contributors to impaired QOL is the symptomatic burden which can range from slight to debilitating. Autonomic dysfunction accounts for a significant proportion of these symptoms, which can be common, non-specific and challenging to treat. Investigating the autonomic nervous system can be straight forward and can assist the clinician to diagnose and treat specific symptoms. Evidence-based treatment options for autonomic symptoms, specifically in CLD, can be lacking and must be extrapolated from other studies and expert opinion. For those with severely impaired quality of life, liver transplantation may offer an improvement; however, more research is needed to confirm this.Keywords: quality of life, treatment, fatigue, angiotensin II

  1. Slowing progression of chronic kidney disease.

    Science.gov (United States)

    Drawz, Paul E; Rosenberg, Mark E

    2013-12-01

    Early identification of chronic kidney disease (CKD) provides an opportunity to implement therapies to improve kidney function and slow progression. The goal of this article is to review established and developing clinical therapies directed at slowing progression. The importance of controlling blood pressure will be discussed along with the target blood pressure that should be achieved in CKD patients. Therapy directed at inhibiting the renin-angiotensin-aldosterone system remains the mainstay of treatment with single-agent inhibition of this system being as good as dual blockade with fewer adverse effects. Other therapies that may be used include correction of metabolic acidosis, dietary protein restriction, and new models for delivering care to patients with CKD. Emerging therapies targeting endothelin, uric acid, kidney fibrosis, and oxidant stress hold promise for the future. PMID:25019022

  2. Invasive Aspergillus infections in hospitalized patients with chronic lung disease

    Directory of Open Access Journals (Sweden)

    Wessolossky M

    2013-05-01

    Full Text Available Mireya Wessolossky,1 Verna L Welch,2 Ajanta Sen,1 Tara M Babu,1 David R Luke21Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA, USA; 2Medical Affairs, Pfizer Inc, Collegeville, PA, USABackground: Although invasive pulmonary aspergillosis (IPA is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lung disease. The purpose of this study was to describe the IPA patient with chronic lung disease and compare the data with that of immunocompromised patients.Methods: The records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lung disease and 56 immunocompromised patients were compared. Patients with chronic lung disease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lung disease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis.Results: Baseline demographics were similar between the two groups. Patients with chronic lung disease were primarily defined by emphysema (61% and asthma (18%, and immunocompromised patients primarily had malignancies (27% and bone marrow transplants (14%. A higher proportion of patients with chronic lung disease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03. The major risk factors for IPA were found to be steroid use in the chronic lung disease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lung disease and immunocompromised patients were cured (P = 0.14; 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75.Conclusion: Nontraditional patients with IPA, such as those with chronic lung disease, have outcomes and mortality similar to that in the

  3. Chronic Kidney Disease in Southwestern Iranian Children

    Directory of Open Access Journals (Sweden)

    Mehrnaz Zangeneh Kamali

    2009-04-01

    Full Text Available Objective: The aim of the study was to determine the etiology of Chronic Kidney Disease (CKD among children attending the pediatric nephrology service at Abuzar children's hospital in Ahvaz city, the referral center in Southwest of Iran.Methods: We reviewed the records of 139 children, diagnosed to have CKD over a 10-year period. CKD was defined a glomerular filtration rate (GFR below 60 ml/1.73 m2/min persisting for more than 3 months.Findings: Among 139 children 81 (58% were males. The mean age at diagnosis of CKD in the patients was 4.2 (±3.6 years. Mean level of serum creatinine at presentation was 1.9 (±1.4 mg/dl. The mean GFR at presentation was 33.5 (±15.4 ml/1.73m2/min while 22% of the patients were already at end stage renal failure indicating that these children were referred too late. Congenital urologic malformation was the commonest cause of CKD present in 70 (50.4% children [reflux nephropathy (23.1%, hypo/dysplastic kidney (15.8%, obstructive uropathy (10.8%, and prune belly syndrome (0.7%]. Other causes included hereditary nephropathies (17.2%, chronic glomerulo-nephritis (6.5%, multisystemic diseases (4.3%, miscellaneous and unknown (each one 10.8%. The mean duration of follow-up was 26 (±24.67 months. Peritoneal or hemodialysis was performed in 10 patients. Six patients underwent (4 live-related and 2 non-related renal transplantation. The rest have died or received standard conservative management for CKD.Conclusion: The commonest causes of CKD were reflux nephropathy, hypo/dysplastic kidney, hereditary nephropathy and obstructive uropathy. Patients presented late, had severe CKD and were malnourished and stunted.

  4. Clinical Practice Guidelines for Severe Chronic Obstructive Pulmonary Disease.

    OpenAIRE

    Niurka Mercedes Galende Hernández; Diosdania Alfonso Falcón; Carlos Alberto Martell Alonso; Alexis Díaz Mesa; Inti Santana Carballosa

    2009-01-01

    Clinical Practice Guidelines for Severe Chronic Obstructive Pulmonary Disease. This concept includes simple chronic bronchitis, asthmatic bronchitis, chronic obstructive bronchitis, and pulmonary emphysema; although this two last are the most commonly included. Risk factors, classification and treatment are commented, stressing the strategy of mechanical ventilation and the indications for mechanical invasive and no invasive ventilation. It includes assessment guidelines focused on the most i...

  5. Preliminary Results on the Feasibility of Using ARFI/SWEI to Assess Cutaneous Sclerotic Diseases.

    Science.gov (United States)

    Lee, Seung Yun; Cardones, Adela R; Doherty, Joshua; Nightingale, Kathryn; Palmeri, Mark

    2015-11-01

    In this study, acoustic radiation force impulse (ARFI) and shear wave elasticity imaging (SWEI) were applied to the skin to investigate the feasibility of their use in assessing sclerotic skin diseases. Our motivation was to develop a non-invasive imaging technology with real-time feedback of sclerotic skin disease diagnosis. This paper shows representative results from an ongoing study, recruiting patients with and without sclerosis. The stiffness of the imaged site was evaluated using two metrics: mean ARFI displacement magnitude and bulk shear wave speed inside the region of interest (ROI). In a subject with localized graft versus host disease (GVHD), the mean ARFI displacement inside sclerotic skin was 61% lower (p types. We conclude ARFI and SWEI can successfully differentiate sclerotic lesions from normal dermis. PMID:26259888

  6. Con: Phosphate binders in chronic kidney disease.

    Science.gov (United States)

    Kestenbaum, Bryan

    2016-02-01

    Phosphate binders are prescribed to chronic kidney disease (CKD) patients based on associations of serum phosphate concentrations with mortality and calcification, experimental evidence for direct calcifying effects of phosphate on vascular smooth muscle tissue and the central importance of phosphate retention in CKD-mineral and bone disorder (CKD-MBD). Current knowledge regarding phosphate metabolism in CKD provides important insight into disease mechanisms and supports future clinical trials of phosphate binders in CKD patients to determine the impact of these medications on clinically relevant outcomes. The risks and benefits of phosphate binders cannot be inferred from association studies of serum phosphate concentrations, which are inconsistent and subject to confounding, animal-experimental data, which are based on conditions that differ from human disease, or physiological arguments, which are limited to known regulatory factors. Many interventions that targeted biochemical pathways suggested by association studies and suspected biological importance have yielded null or harmful results. Clinical trials of phosphate binders are of high clinical and scientific importance to nephrology. Demonstration of reduced rates of clinical disease in such trials could lead to important health benefits for CKD patients, whereas negative results would refocus efforts to understand and treat CKD-MBD. Clinical trials that employ highly practical or 'pragmatic' designs represent an optimal approach for determining the safety and effectiveness of phosphate binders in real-world settings. Absent clinical trial data, observational studies of phosphate binders in large CKD populations could provide important information regarding the benefits, risks and/or unintended side effects of these medications. PMID:26681747

  7. Protective effect of Linomide on murine systemic lupus erythematosus (SLE)

    Institute of Scientific and Technical Information of China (English)

    Zhi-yongXIAO; Wen-xiaZHOU; Yong-xiangZHANG; Jun-fengHE; Liu-hongYUN

    2004-01-01

    Linomide, a quinoline-3-carboxamide, has a pleiotropic immune modulating capacity and inhibits development as well asprogression of disease in animal models of autoimmunity. Its benefical effects on experimental autoimmune disease models have been linked to regulation of Th 1/Th2 balance and alter macrophage functions. We studied the effect of linomide on chronic graft-versus-host disease model mice. The oral administration of

  8. L'Azacytidine comme traitement de la maladie du greffon contre l'hôte de type chronique sclérodermique expérimentale.

    OpenAIRE

    Fransolet, Gilles; Ehx, Grégory; Somja, Joan; Hannon, Muriel; Dubois, Sophie; Drion, Pierre; Caers, Jo; Humblet-Baron, Stéphanie; Belle, Ludovic; Delvenne, Philippe; Beguin, Yves; Conteduca, Giuseppina; Baron, Frédéric

    2015-01-01

    Introduction: Graft-versus-host disease (GVHD) has remained a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) for the last decades. Following unmanipulated peripheral-blood stem cell transplantation, 60% of the patients experience chronic GVHD while approximately 15% of them develop a sclerodermic form of chronic GVHD characterized by multiple organ fibrosis and loss of skin elasticity. Regulatory T cells (Tregs) play a pivotal protective role in the pathogenes...

  9. Chronic Respiratory Diseases of School-Age Children

    Science.gov (United States)

    McGovern, John P.

    1976-01-01

    The author examines the problems of chronic respiratory disease in school-age children from a medical viewpoint, including recognition and diagnosis, commonly encountered diseases, their effect on participation in physical exercise, emotional factors, medication, and emergency care. (MB)

  10. Molecular diagnosis of chronic granulomatous disease.

    Science.gov (United States)

    Roos, D; de Boer, M

    2014-02-01

    Patients with chronic granulomatous disease (CGD) suffer from recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, liver, brain and bones. Frequently found pathogens are Staphylococcus aureus, Aspergillus species, Klebsiella species, Burkholderia cepacia and Salmonella species. CGD is a rare (∼1:250 000 births) disease caused by mutations in any one of the five components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. This enzyme generates superoxide and is essential for intracellular killing of pathogens by phagocytes. Molecular diagnosis of CGD involves measuring NADPH oxidase activity in phagocytes, measuring protein expression of NADPH oxidase components and mutation analysis of genes encoding these components. Residual oxidase activity is important to know for estimation of the clinical course and the chance of survival of the patient. Mutation analysis is mandatory for genetic counselling and prenatal diagnosis. This review summarizes the different assays available for the diagnosis of CGD, the precautions to be taken for correct measurements, the flow diagram to be followed, the assays for confirmation of the diagnosis and the determinations for carrier detection and prenatal diagnosis. PMID:24016250

  11. Building the chronic kidney disease management team.

    Science.gov (United States)

    Spry, Leslie

    2008-01-01

    The need to be efficient and the demands for performance-based service are changing how nephrologists deliver care. Chronic kidney disease (CKD) occurs in patients with complex medical and social problems. CKD management requires that multidisciplinary professionals provide patient education, disease management, and psychosocial support. To remain cost-efficient, many physicians are training and supervising midlevel practitioners in the delivery of specialized health care. Specialized care that meets present CKD patient needs is best delivered in a CKD clinic. Three models of CKD clinic are identified: (1) anemia management CKD clinic, (2) the basic CKD clinic, and (3) the comprehensive CKD clinic. Each clinic model is based on critical elements of staffing, billable services, and patient-focused health care. Billable services are anemia-management services, physician services that may be provided by midlevel practitioners, and medical nutrition therapy. In some cases, social worker services may be billable. Building a patient-focused clinic that offers CKD management requires planning, familiarity with federal regulations and statutes, and skillful practitioners. Making services cost-efficient and outcome oriented requires careful physician leadership, talented midlevel practitioners, and billing professionals who understand the goals of the CKD clinic. As Medicare payment reforms evolve, a well-organized CKD program can be well poised to meet the requirements of payers and congressional mandates for performance-based purchasing.

  12. Optimism's explicative role for chronic diseases

    Directory of Open Access Journals (Sweden)

    Giulia eAvvenuti

    2016-03-01

    Full Text Available The increasing interest about dispositional optimism's role in health status and its positive modulating effect on health outcomes has led to a remarkable scientific production in the last decade. To date lot is known about which fields of medicine are affected by optimism, instead much less is known about how optimism interacts with other factors, both biological and psychological, in determining health status. The aim of this mini review is to explore the literature derived from clinical and experimental research assessing the associations between dispositional optimism and health status. Dispositional optimism can be considered as facet of personality that is cognitive in nature which holds the global expectation that the future will be plenty of good events. Optimists view desired goals as obtainable, so they often confront adversities in active manners resulting in perseverance and increased goal attainment. Only studies that explicitly included optimism and health outcomes, as measurable variables, and that reported a clear association between them have been reviewed. Cancer, cardiovascular disease, respiratory failure and ageing with multimorbidity were considered. Among the possible explicative hypotheses, two seem to best describe results: optimism may have a direct effect on the neuroendocrine system and on immune responses, and it may have an indirect effect on health outcomes by promoting protective health behaviors, adaptive coping strategies and enhancing positive mood. The research on optimism and health status has already shed light on important mechanisms regarding chronic diseases' management, however further studies are needed to deepen the knowledge.

  13. Vegetarian diets, chronic diseases and longevity.

    Science.gov (United States)

    Ginter, E

    2008-01-01

    Vegetarians form a non-homogenous group consisting of semivegetarians (plant food, dairy products, eggs and fish), lacto-ovo vegetarians (plant food, dairy products, eggs) and vegans (plant food only). According to pure vegetarian ideologists, people consuming vegetarian diet have better health and live longer than nonvegetarians, because persons consuming milk, dairy products, meat, eggs and fish are at health risk. In fact the most healthy people in Europe are inhabitants of Iceland, Switzerland and Scandinavia, consuming great amounts of food of animal origin. Meta-analysis of several prospective studies showed no significant differences in the mortality caused by colorectal, stomach, lung, prostate or breast cancers and stroke between vegetarians and "health-conscious" nonvegetarians. In vegetarians, a decrease of ischemic heart disease mortality was observed probably due to lower total serum cholesterol levels, lower prevalence of obesity and higher consumption of antioxidants. Very probably, an ample consumption of fruits and vegetables and not the exclusion of meat make vegetarians healthful. Now, the largest cohort study of diet and health on more than half million of persons, the European Prospective Investigation into Cancer and Nutrition (EPIC) study, will bring new data on the relationships between diet, lifestyle and environmental factors and the incidence of cancer, cardiovascular and other chronic diseases. Vegetarianism is a form of food restriction; and in our overfed society, food restriction is a plus unless it results in a nutritional deficiency (Fig. 1, Tab. 2, Ref. 18). PMID:19166134

  14. Chronic kidney disease and the skeleton.

    Science.gov (United States)

    Miller, Paul D

    2014-01-01

    Fractures across the stages of chronic kidney disease (CKD) could be due to osteoporosis, some form of renal osteodystrophy defined by specific quantitative histomorphometry or chronic kidney disease-mineral and bone disorder (CKD-MBD). CKD-MBD is a systemic disease that links disorders of mineral and bone metabolism due to CKD to either one or all of the following: abnormalities of calcium, phosphorus, parathyroid hormone or vitamin D metabolism; abnormalities in bone turnover, mineralization, volume, linear growth or strength; or vascular or other soft-tissue calcification. Osteoporosis, as defined by the National Institutes of Health, may coexist with renal osteodystrophy or CKD-MBD. Differentiation among these disorders is required to manage correctly the correct disorder to reduce the risk of fractures. While the World Health Organization (WHO) bone mineral density (BMD) criteria for osteoporosis can be used in patients with stages 1-3 CKD, the disorders of bone turnover become so aberrant by stages 4 and 5 CKD that neither the WHO criteria nor the occurrence of a fragility fracture can be used for the diagnosis of osteoporosis. The diagnosis of osteoporosis in stages 4 and 5 CKD is one of the exclusion-excluding either renal osteodystrophy or CKD-MBD as the cause of low BMD or fragility fractures. Differentiations among the disorders of renal osteodystrophy, CKD-MBD or osteoporosis are dependent on the measurement of specific biochemical markers, including serum parathyroid hormone (PTH) and/or quantitative bone histomorphometry. Management of fractures in stages 1-3 CKD does not differ in persons with or without CKD with osteoporosis assuming that there is no evidence for CKD-MBD, clinically suspected by elevated PTH, hyperphosphatemia or fibroblast growth factor 23 due to CKD. Treatment of fractures in persons with osteoporosis and stages 4 and 5 CKD is not evidence-based, with the exception of post-hoc analysis suggesting efficacy and safety of specific

  15. ANESTHETIC CONSIDERATION S IN CHRONIC OBSTRUCTIVE PULMON ARY DISEASE

    Directory of Open Access Journals (Sweden)

    Awati

    2015-03-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a spectrum of diseases that includes emphysema, chronic bronchitis, and small airway disease. It i s characterized by progressive increased resistance to breathing. Patients with marked obstructive pulmonary disease are at increased risk for both intraoperative and Postoperative pulmonary complications. These patients require thorough preoperative prepa ration, meticulous intraoperative management & postoperative care. This article describes anesthetic considerations in a patient with COPD.

  16. Clinical Scenarios in Chronic Kidney Disease: Parenchymal Chronic Renal Diseases - Part 2.

    Science.gov (United States)

    Petrucci, Ilaria; Samoni, Sara; Meola, Mario

    2016-01-01

    Secondary nephropathies can be associated with disreactive immunological disorders or with a non-inflammatory glomerular damage. In systemic lupus erythematosus (SLE), scleroderma and rheumatoid arthritis as in other connective tissue diseases, kidney volume and cortex echogenicity are the parameters that best correlate with clinical severity of the disease, even if the morphological aspect is generally non-specific. Doppler studies in SLE document the correlation between resistance indexes (RIs) values and renal function. Acquired immunodeficiency syndrome (HIV) causes different types of renal damage. At ultrasound (US), kidneys have almost a normal volume, while during superinfection they enlarge (coronal diameter >13 cm) and become globular, loosing their normal aspect. Cortex appears highly hyperechoic, uniform or patchy. Microcalcifications of renal cortex and medulla are a US sign that can suggest HIV. In amyloidosis, kidneys appear normal or increased in volume in the early stages of disease. Renal cortex is diffusely hyperechoic and pyramids can show normal size and morphology, but more often they appear poorly defined and hyperechoic. RIs are very high since the early stages of the disease. Nephromegaly with normal kidney shape is the first sign of lymphoma or multiple myeloma. In systemic vasculitis, renal cortex is diffusely hyperechoic, while pyramids appear hypoechoic and globular due to interstitial edema. When vasculitis determines advanced chronic kidney disease stages, kidneys show no specific signs. Microcirculation damage is highlighted by increased RIs values >0.70 in the chronic phase. PMID:27169551

  17. Chronic lower respiratory diseases among demolition and cement workers

    DEFF Research Database (Denmark)

    Mølgaard, Ellen Fischer; Hannerz, Harald; Tüchsen, Finn;

    2013-01-01

    To estimate standardised hospitalisation ratios (SHR) for chronic lower respiratory diseases among demolition and cement workers in Denmark, 1995-2009.......To estimate standardised hospitalisation ratios (SHR) for chronic lower respiratory diseases among demolition and cement workers in Denmark, 1995-2009....

  18. Chronic Disease and Sexuality : A Generic Conceptual Framework

    NARCIS (Netherlands)

    Verschuren, Jesse E. A.; Enzlin, Paul; Dijkstra, Pieter U.; Geertzen, Jan H. B.; Dekker, Rienk

    2010-01-01

    Although sexual dysfunctions are frequently comorbid with many chronic diseases and their treatments, until recently, these dysfunctions have been neglected in both research and clinical practice. Fortunately, sexual functioning in the context of chronic disease has now begun to receive more scienti

  19. Predictors of objective cough frequency in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Sumner, Helen; Woodcock, Ashley; Kolsum, Umme;

    2013-01-01

    Cough is one of the principal symptoms of chronic obstructive pulmonary disease (COPD) but the potential drivers of cough are likely to be multifactorial and poorly understood.......Cough is one of the principal symptoms of chronic obstructive pulmonary disease (COPD) but the potential drivers of cough are likely to be multifactorial and poorly understood....

  20. Prevalence of Chronic Diseases in Adolescents with Intellectual Disability

    Science.gov (United States)

    Oeseburg, B.; Jansen, D. E. M. C.; Dijkstra, G. J.; Groothoff, J. W.; Reijneveld, S. A.

    2010-01-01

    Valid community-based data on the prevalence of chronic diseases in adolescents (12-18 years) with intellectual disability (ID-adolescents) are scarce. The aim of this study was to assess the prevalence rates and the nature of chronic diseases in a population of ID-adolescents and to compare them with the rates among adolescents in the general…