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https://www.readbyqxmd.com/read/28717861/patient-perspectives-on-gene-transfer-therapy-for-sickle-cell-disease
#1
Heather Strong, Monica J Mitchell, Alana Goldstein-Leever, Lisa Shook, Punam Malik, Lori E Crosby
INTRODUCTION: Sickle cell disease (SCD) is a chronic genetic disease with high morbidity and early mortality; it affects nearly 100,000 individuals in the USA. Bone marrow transplantation, the only curative treatment, is available to less than 20% of patients because of a number of access barriers. Gene transfer therapy (GTT) has been shown to be curative in animal models and is approved for use in humans for early-phase studies at a few centers. GTT would offer a more accessible treatment option available to all patients...
July 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28713390/hematopoietic-stem-cell-transplantation-in-an-infant-with-immunodeficiency-centromeric-instability-and-facial-anomaly-syndrome
#2
Katharina L Gössling, Cyrill Schipp, Ute Fischer, Florian Babor, Gerhard Koch, Friedhelm R Schuster, Jutta Dietzel-Dahmen, Dagmar Wieczorek, Arndt Borkhardt, Roland Meisel, Michaela Kuhlen
Immunodeficiency, centromeric instability, and facial anomaly (ICF) syndrome is a rare autosomal recessive genetic condition with severe immunodeficiency, which leads to lethal infections if not recognized and treated in early childhood. Up-to-date treatment regimens consist of prophylactic and supportive treatment of the recurrent infections. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28712678/impact-of-the-18th-birthday-on-waitlist-outcomes-among-young-adults-listed-for-heart-transplant-a-regression-discontinuity-analysis
#3
David M Peng, Qiuying Qu, Nancy McDonald, Seth A Hollander, Daniel Bernstein, Katsuhide Maeda, Beth D Kaufman, David N Rosenthal, Doff B McElhinney, Christopher S Almond
BACKGROUND: Patients listed for heart transplant after their 18th birthday purportedly wait longer to receive a donor heart compared with patients listed before their 18th birthday. It is unclear whether there is an actual difference in wait times and whether any difference in wait time is associated with lower likelihood of transplant and/or higher risk of mortality. METHODS: Organ procurement and transplant network data were used to identify all patients listed for heart transplant between 2006 and 2014 within a 1-year period before and after their 18th birthday...
May 19, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28708333/conversion-from-calcineurin-inhibitors-to-mtor-inhibitors-as-primary-immunosuppressive-drugs-in-pediatric-heart-transplantation
#4
Alfred Asante-Korang, Jennifer Carapellucci, Diane Krasnopero, Abigail Doyle, Brian Brown, Ernest Amankwah
There are only a few reports of successful use of mammalian target of rapamycin (mTORI) as primary immunosuppression in pediatric heart transplantation. Compared to calcineurin inhibitors, mTORI have less side effects, especially nephrotoxicity, infections and malignancies. A retrospective study was conducted at our institution of all 170 heart transplants from 1995-2015. Nineteen patients were switched from tacrolimus(n=15) or cyclosporin(n=4) to everolimus(n=4) or sirolimus(n=15) due to nephrotoxicity(n=5), malignancy(n=8), EBV viremia/reactive plasmacytic changes(n=5) and immune hemolytic anemia(n=1)...
July 14, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28707282/a-system-to-identify-inhibitors-of-mtor-signaling-using-high-resolution-growth-analysis-in-saccharomyces-cerevisiae
#5
Mitchell B Lee, Daniel T Carr, Michael G Kiflezghi, Yan Ting Zhao, Deborah B Kim, Socheata Thon, Margarete D Moore, Mary Ann K Li, Matt Kaeberlein
The mechanistic target of rapamycin (mTOR) is a central regulator of growth and proliferation and mTOR inhibition is a promising therapy for a variety of diseases and disorders. Inhibition of mTOR complex I (mTORC1) with rapamycin delays aging and increases healthy longevity in laboratory animals and is used clinically at high doses to prevent organ transplant rejection and to treat some forms of cancer. Clinical use of rapamycin is associated with several unwanted side effects, however, and several strategies are being taken to identify mTORC1 inhibitors with fewer side effects...
July 13, 2017: GeroScience
https://www.readbyqxmd.com/read/28706973/splenocyte-infusion-and-whole-body-irradiation-for-induction-of-peripheral-tolerance-in-porcine-lung-transplantation-modifications-of-the-preconditioning-regime-for-improved-clinical-feasibility
#6
Katharina Jansson, Karla Dreckmann, Wiebke Sommer, Murat Avsar, Jawad Salman, Thierry Siemeni, Ann-Kathrin Knöfel, Linda Pauksch, Jens Gottlieb, Jörg Frühauf, Martin Werner, Danny Jonigk, Martin Strüber, Axel Haverich, Gregor Warnecke
BACKGROUND: Preoperative low-dose whole-body irradiation (IRR) with 1.5 and 7 Gy thymic IRR of the recipient, combined with a perioperative donor splenocyte infusion lead to reliable donor specific peripheral tolerance in our allogeneic porcine lung transplantation model. To reduce the toxicity of this preconditioning regime, modifications of the IRR protocol and their impact on allograft survival were assessed. METHODS: Left-sided single lung transplantation from major histocompatibility complex and sex mismatched donors was performed in 14 adult female minipigs...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28701922/bone-marrow-mesenchymal-stem-cell-transplantation-promotes-functional-improvement-associated-with-cntf-stat3-activation-after-hemi-sectioned-spinal-cord-injury-in-tree-shrews
#7
Liu-Lin Xiong, Fei Liu, Bing-Tuan Lu, Wen-Ling Zhao, Xiu-Juan Dong, Jia Liu, Rong-Ping Zhang, Piao Zhang, Ting-Hua Wang
Hemi-sectioned spinal cord injury (hSCI) can lead to spastic paralysis on the injured side, as well as flaccid paralysis on the contralateral side, which can negatively affect a patient's daily life. Stem-cell therapy may offer an effective treatment option for individuals with hSCI. To examine the role of bone marrow mesenchymal stem cells (BMSCs) transplantation on hSCI and explore related mechanisms in the tree shrews, here, we created a model of hSCI by inducing injury at the tenth thoracic vertebra (T10)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28699692/granulocyte-colony-stimulating-factor-administration-among-hemoglobin-s-trait-donors-a-single-center-experience-from-the-eastern-mediterranean-region
#8
Cigdem Gereklioglu, Suheyl Asma, Aslı Korur, Songul Tepebası, Pelin Aytan, Mahmut Yeral, Ilknur Kozanoglu, Can Boga, Hakan Ozdogu
BACKGROUND AND OBJECTIVE: Assessment of Hemoglobin S trait donors has gained importance together with the increased allogeneic peripheral stem cell transplant activity for sickle cell disease in the regions where the disease is prevalent. Outcomes of Granulocyte-Colony Stimulating Factor (G-CSF) administration are obscure for hemoglobin S trait donors. This study aims at investigating the incidence of hemoglobin S carrier status and outcomes of G-CSF administration among donors who live in Eastern Mediterranean region...
July 12, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28695658/fecal-microbial-transplantation-in-inflammatory-bowel-disease-a-movement-too-big-to-be-ignored
#9
M Laffin, K L Madsen
The development of new therapies for inflammatory bowel disease is plagued by high costs, potential side effects, and variable levels of effectiveness. Fecal microbial transplant in inflammatory bowel diseases can offer an alternative to traditionally developed pharmacologic therapies and has demonstrated the ability to induce disease remission in randomized control trials. However, questions remain about the ultimate role of this therapy in disease management, including long term safety, and the optimal composition of transplanted stool...
July 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28691943/effect-of-a-new-matrix-therapy-agent-in-persistent-epithelial-defects-after-bacterial-keratitis-treated-with-topical-fortified-antibiotics
#10
Marc-Antoine Chappelet, Diane Bernheim, Christophe Chiquet, Florent Aptel
PURPOSE: To evaluate the effect of topical application of a matrix regenerating agent (RGTA) in subjects with a persistent epithelial defect after bacterial keratitis treated with topical fortified antibiotics. METHODS: In this prospective case series of 14 subjects (14 eyes) with a persisting corneal ulcer after the cessation of fortified antibiotics, subjects were treated with an RGTA at a dose of 1 drop every other day. The main outcome measure was the proportion of subjects with complete corneal healing 1 month after initiation of treatment...
July 6, 2017: Cornea
https://www.readbyqxmd.com/read/28689433/experimental-and-early-investigational-drugs-for-androgenetic-alopecia
#11
Hongwei Guo, Wendi Victor Gao, Hiromi Endo, Kevin John McElwee
Treatments for androgenetic alopecia constitute a multi-billion-dollar industry, however, currently available therapeutic options have variable efficacy. Consequently, in recent years small biotechnology companies and academic research laboratories have begun to investigate new or improved treatment methods. Research and development approaches include improved formulations and modes of application for current drugs, new drug development, development of cell-based treatments, and medical devices for modulation of hair growth...
July 12, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28686294/nfat-regulated-cytokine-gene-expression-during-tacrolimus-therapy-early-after-renal-transplantation
#12
Sara Bremer, Nils T Vethe, Morten Skauby, Margrete Kasbo, Elisabet D Johansson, Karsten Midtvedt, Stein Bergan
AIMS: Despite pharmacokinetic monitoring of calcineurin inhibitors, the long-term outcome after transplantation (Tx) is still hampered by the side effects of these drugs. The aim of this study was to characterize the nuclear factor of activated T cells (NFAT)-regulated gene expression as a potential pharmacodynamic biomarker for further individualization of tacrolimus (Tac) therapy. METHODS: In 29 renal allograft recipients samples were drawn once pre-Tx, and before and 1...
July 7, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28685630/the-potential-role-of-fecal-microbiota-transplantation-in-the-treatment-of-inflammatory-bowel-disease
#13
Maitham Abbas Khajah
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of an unknown etiology. Its pathogenesis involves an interplay of infectious, genetic, environmental, and immunological factors. The current therapeutic options have various limitations in terms of cost, side effect profile, and the development of drug resistance and dependence. Therefore, there is a need to develop future therapeutic options which are safe and effective to control the inflammatory process. This review focuses in a method for the administration of fecal matters (which contains a mixture of various commensals) from a healthy donor to the inflamed colon called fecal microbiota transplantation (FMT) aiming to correct the underlying dysbiosis in the gut as one of the major driving force for the inflammatory process...
July 7, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28685218/influence-of-cyp2c19-genotypes-on-the-occurrence-of-adverse-drug-reactions-of-voriconazole-among-hematological-patients-after-allo-hsct
#14
Beata Sienkiewicz, Donata Urbaniak-Kujda, Jarosław Dybko, Andrzej Dryś, Magdalena Hurkacz, Tomasz Wróbel, Anna Wiela-Hojeńska
The aim of this study was to determine the influence of different CYP2C19 genotypes on selected liver function parameters, and ADR occurrence during VCZ prophylaxis in adult patients after allo-HSCT (allogeneic hematopoietic stem cell transplantation). CYP2C19 mutations were determined in a cohort of 30 adults using PCR-RFLP methods established by Sim et al. and Goldstein and Blaisdell. The patients' protocol included biometrical and biochemical data, information on the underlying disease, chemotherapy, molds infections occurring during VCZ treatment, adverse drug reactions typical for the use of voriconazole, and probable drug - drug interactions...
July 6, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28684893/safety-and-feasibility-of-autologous-mesenchymal-stem-cell-transplantation-in-chronic-stroke-in-indian-patients-a-four-year-follow-up
#15
Ashu Bhasin, Senthil S Kumaran, Rohit Bhatia, Sujata Mohanty, M V Padma Srivastava
Introduction: Stem cell (SC) therapy has been envisioned as a therapeutic vehicle to promote recovery in resistant neurological diseases. Knowing the logistics and paradigms in recovery processes after Stroke, clinicians have pioneered the transplantation therapy. This study presents four-year follow up of our previous trial transplanting bone-marrow-derived animal-free culture expanded intravenous mesenchymal stem cells (MSCs) in chronic stroke which was published in 2010. Methods: We performed an open-label, pilot trial on 12 patients with chronic stroke...
2017: Journal of Stem Cells & Regenerative Medicine
https://www.readbyqxmd.com/read/28681147/therapeutic-effect-of-icariin-combined-with-stem-cells-on-postmenopausal-osteoporosis-in-rats
#16
Dao Tang, Cuiling Ju, Yanjie Liu, Fei Xu, Zhengguang Wang, Dongbo Wang
Osteoporosis is characterized by skeletal fragility and microarchitectural deterioration. The side effects of drugs to treat osteoporosis will negatively affect the health of patients. This study aimed to investigate the therapeutic effects of icariin combined with adipose-derived stem cells on osteoporosis in a postmenopausal osteoporosis model after ovariectomy in rats. After ovariectomy the rats were treated with icariin combined with adipose-derived stem cell transplantation. The levels of alkaline phosphatase, tartrate-resistant acid phosphatase, osteoprotegerin, and bone γ-carboxyglutamate protein in serum were determined by ELISA...
July 5, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28675459/stimulation-of-adrenergic-activity-by-desipramine-enhances-hematopoietic-stem-and-progenitor-cell-mobilization-along-with-g-csf-in-multiple-myeloma-a-pilot-study
#17
Aditi Shastri, Anjali Budhathoki, Stefan K Barta, Noah Kornblum, Olga Derman, Ramakrishna Battini, Radha Ragupathy, Amit Verma, Paul S Frenette, Ira Braunschweig, Murali Janakiram
Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G-CSF resulted in improved HSC mobilization. Here we present the results of an open-label single-arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G-SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics...
July 4, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28673584/parp-inhibitors-in-acute-myeloid-leukaemia-therapy-how-a-synthetic-lethality-approach-can-be-a-valid-therapeutic-alternative
#18
Grigore Aristide Gafencu, Ciprian Ionuț Tomuleasa, Gabriel Ghiaur
Acute myeloid leukaemia (AML) is a malignancy in need of new therapeutic options. The current standard of care chemotherapy, leads to complete remission (CR) in the vast majority of adult patients under the age of 60. In contrast, CR rates in patients over the age of 60 reaches only 40-60%. While achievement of a CR is an important stepping stone in the treatment of AML, the majority of these patients experience relapse and die of their disease without adequate consolidation chemotherapy. Blood and marrow transplantation (BMT) can improve outcome in a select patient with AML but unfortunately, it is not a valid treatment option for the majority of older patients...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28672061/thalidomide-treatment-prevents-chronic-graft-rejection-after-aortic-transplantation-in-rats
#19
Katharine K Miller, Dong Wang, Xiaomeng Hu, Xiaoqin Hua, Tobias Deuse, Evgenios Neofytou, Thomas Renne, Joachim Velden, Hermann Reichenspurner, Sonja Schrepfer, Daniel Bernstein
BACKGROUND: Cardiac allograft vasculopathy (CAV) affects approximately 30% of cardiac transplant patients at five years post-transplantation. To date there are few CAV treatment or prevention options, none of which are highly effective. The aim of the study was to investigate the effect of thalidomide on the development of CAV. METHODS: The effect of thalidomide treatment on chronic rejection was assessed in rat orthotopic aortic transplants in allogeneic F344 or syngeneic Lew rats (n=6/group)...
July 3, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28671056/protein-kinase-inhibitors-as-therapeutic-drugs-in-aml-advances-and-challenges
#20
Yuan Ling, Zikang Zhang, Hua Zhang, Zunnan Huang
Acute myeloid leukemia (AML) is a malignant blood disorder and the cure rate has been remarkably improved over the past decade. However, recurrent or refractory leukemia remains the major problem of the AML and no clearly effective therapy has been established so far. Traditional treatments such as chemotherapy and hematopoietic stem cell transplantation are both far dissatisfying the patients partly for their individual variety. Besides, conventional treatments usually have many side effects to result in poor prognosis...
July 3, 2017: Current Pharmaceutical Design
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