Academic literature on the topic 'Transplants; Immunosuppression; Grafts'
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Journal articles on the topic "Transplants; Immunosuppression; Grafts"
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Kernan, NA, C. Bordignon, G. Heller, I. Cunningham, H. Castro-Malaspina, B. Shank, N. Flomenberg, J. Burns, SY Yang, and P. Black. "Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants." Blood 74, no. 6 (November 1, 1989): 2227–36. http://dx.doi.org/10.1182/blood.v74.6.2227.bloodjournal7462227.
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Risk factors for graft failure were analyzed in 122 recipients of an allogeneic T-cell-depleted human leukocyte antigen (HLA)-identical sibling marrow transplant as treatment for leukemia. In each case pretransplant immunosuppression included 1,375 to 1,500 cGy hyperfractionated total body irradiation and cyclophosphamide (60 mg/kg/d x 2). No patient received immunosuppression prosttransplant for graft-versus-host disease (GVHD) prophylaxis. Nineteen patients in this group experienced graft failure. The major factors associated with graft failure were transplants from male donors and the age of the patient (or donor). Among male recipients of male donor-derived grafts a low dose per kilogram of nucleated cells, progenitor cells (colony forming unit-GM) and T cells was also associated with graft failure. Additional irradiation to 1,500 cGy, high dose corticosteroids posttransplant, and additional peripheral blood donor T cells did not decrease the incidence of graft failure. In addition, type of leukemia, time from diagnosis to transplant, an intact spleen, or the presence of antidonor leukocyte antibodies did not correlate with graft failure. To ensure engraftment of secondary transplants, further immunosuppression was necessary but was poorly tolerated. However, engraftment and survival could be achieved with an immunosuppressive regimen in which antithymocyte globulin and high dose methylprednisolone were administered both before and after infusions of secondary partially T- cell-depleted marrow grafts.
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Kernan, NA, C. Bordignon, G. Heller, I. Cunningham, H. Castro-Malaspina, B. Shank, N. Flomenberg, J. Burns, SY Yang, and P. Black. "Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants." Blood 74, no. 6 (November 1, 1989): 2227–36. http://dx.doi.org/10.1182/blood.v74.6.2227.2227.
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Abstract Risk factors for graft failure were analyzed in 122 recipients of an allogeneic T-cell-depleted human leukocyte antigen (HLA)-identical sibling marrow transplant as treatment for leukemia. In each case pretransplant immunosuppression included 1,375 to 1,500 cGy hyperfractionated total body irradiation and cyclophosphamide (60 mg/kg/d x 2). No patient received immunosuppression prosttransplant for graft-versus-host disease (GVHD) prophylaxis. Nineteen patients in this group experienced graft failure. The major factors associated with graft failure were transplants from male donors and the age of the patient (or donor). Among male recipients of male donor-derived grafts a low dose per kilogram of nucleated cells, progenitor cells (colony forming unit-GM) and T cells was also associated with graft failure. Additional irradiation to 1,500 cGy, high dose corticosteroids posttransplant, and additional peripheral blood donor T cells did not decrease the incidence of graft failure. In addition, type of leukemia, time from diagnosis to transplant, an intact spleen, or the presence of antidonor leukocyte antibodies did not correlate with graft failure. To ensure engraftment of secondary transplants, further immunosuppression was necessary but was poorly tolerated. However, engraftment and survival could be achieved with an immunosuppressive regimen in which antithymocyte globulin and high dose methylprednisolone were administered both before and after infusions of secondary partially T- cell-depleted marrow grafts.
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Self, Michael, Ernest Dunn, John Cox, and Karl Brinker. "Managing Breast Cancer in the Renal Transplant Patient: A Unique Dilemma." American Surgeon 72, no. 2 (February 2006): 150–53. http://dx.doi.org/10.1177/000313480607200211.
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Improvements in immunosuppression have increased patient and graft survival in transplant recipients. As a result, there is greater risk of neoplastic processes such as breast cancer. Treatment in this population is complicated by the necessary immunosuppression, vascular accesses, and transplant grafts. General surgeons may expect to encounter more of these complex patients in the community setting. We sought to evaluate the surgical treatment of breast cancer in patients with renal transplants. Hospital and private physician records were queried to identify patients who developed breast cancer after a renal or pancreatic/renal transplantation. These charts were reviewed for demographics, type of breast cancer and treatment, location of dialysis access, and complications. From June 1, 1994, to May 31, 2004, 14 patients were identified. Eight patients had functioning transplants. All patients underwent operative interventions. Ten patients underwent adjuvant treatment. Three had functioning transplants and chose not to risk the graft with cessation of immunotherapy. However, no patient with functioning transplants who underwent chemotherapy developed organ failure. Breast cancer after transplantation poses a unique dilemma. The threat of transplanted organ failure is a major concern to these patients and often supersedes adjuvant therapies.
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Trumble, Thomas E. "Peripheral Nerve Transplantation: The Effects of Predegenerated Grafts and Immunosuppression." Journal of Neural Transplantation and Plasticity 3, no. 1 (1992): 39–49. http://dx.doi.org/10.1155/np.1992.39.
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Research involving nerve transplantation has shown that tissue rejection limits the neurologic recovery unless the host is immunosuppressed. This study investigates an alternative to permanent or temporary immunosuppression using a rat model with nerve transplants from Brown- Norway rat donors to bridge defects in the sciatic nerve of Lewis rat recipients as these two inbred strains differ at both major and minor histocompatibility loci.The specific aim of this study was to evaluate if predegenerated nerve grafts decreased the tissue rejection and improved the neurologic recovery of animals with allogenic nerve grafts to avoid the problems associated with either short- or long-term immunosuppression. The animals in the experimental groups received cyclosporin-A, predegencrated grafts, both, or neither. The predegenerated grafts were produced by division of the nerve three weeks prior to grafting to allow for Wallerian degeneration to occur. The outcome was assessed by measurements stressing functional recovery (sensory testing, gait analysis, joint flexion contracture), studies of muscle recovery (muscle weight and hydroxyproline concentration), and histologic studies (axonal counts and inflammatory reaction). The animals receiving the predegenerated grafts without cyclosporin did have an improved recovery (joint flexion contracture 35° ± 8 ° and hydroxyproline ratio 1.52 ± 0.16) as compared to the joint flexion contractures and hydroxyproline ratios of the allograft group of animals without either cyclosporin- A or pretreatment and the ungrafted control group (47° ± 18°, 1.68 ± 0.34, and 53° ±15° ,4.50 ± 0.27, respectively, p < 0.01). However, all the isograft groups and allograft groups with cyclosporin-A, regardless of whether the graft had been predegenerated or not, had greater neurologic recovery than the allograft group with predegenerated grafts but without cyclosporin-A by the same parameters (p < 0.01). Allograft groups with short-term immunosuppression with cyclosporin-A did as well as isograft groups, and isograft groups with predegenerated grafts did not do any better than isografts without pretreatment (p <0.01).Clinical Relevance:Predegenerated nerve allografts will allow for greater neurologic recovery than standard nerve allografts avoiding the complications of immunosuppression, but the level of recovery is less than that of recipients of nerve allografts with immunosuppression. Nerve transplants would avoid the problems of neurologic deficits at the donor site and allow multiple large deficits to be treated easily.
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Mathes, David, Scott Stoll Graves, George E. Georges, Christian Kuhr, Jeff Chang, Tiffany Butts, and Rainer Storb. "Long-Term Tolerance to Kidney Allografts After Induced Rejection of Donor Hematopoietic Chimerism in a Preclinical Canine Model." Blood 120, no. 21 (November 16, 2012): 2991. http://dx.doi.org/10.1182/blood.v120.21.2991.2991.
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Abstract Abstract 2991 Allogeneic hematopoietic cell transplantation provides a reliable method for inducing tolerance towards solid organ grafts. However, this procedure can result in graft-versus-host disease (GVHD) thereby limiting its application. Here we test the hypothesis that mixed chimerism can be intentionally reverted to host hematopoiesis without rejection of a kidney graft. Recipient dogs were given 2 Gy total body irradiation (TBI) before and a short course of immunosuppression after marrow infusion from dog leukocyte antigen-identical littermates. All dogs achieved stable mixed chimerism. After a mean of 20 weeks, one cohort of dogs received kidney transplants from their respective marrow donors. Subsequently, recipients were reconditioned with 2 Gy TBI and given autologous granulocyte-colony stimulating factor-mobilized leukocytes (recipient leukocyte infusion) that had been collected before marrow transplant. Dogs receiving a second TBI and recipient leukocyte infusion without a kidney transplant rejected their donor hematopoietic graft within 3 weeks. Dogs that received kidney grafts, followed by a second TBI and recipient leukocyte infusion, rejected their marrow graft without rejecting their transplanted kidneys for periods greater than one year. Mixed chimerism may be clinically reverted to 100% recipient without rejection of a kidney allograft. This model has potential applications in understanding the mechanism of split tolerance. This finding may have application towards minimizing the risk of GVHD in solid organ transplant patients given hematopoietic cell transplantation from HLA-identical donors. Disclosures: No relevant conflicts of interest to declare.
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Kjøsen, Gisle, Kristina Rydenfelt, Rune Horneland, Einar Martin Aandahl, Pål-Dag Line, Eric Dorenberg, Audun Elnæs Berstad, et al. "Early detection of complications in pancreas transplants by microdialysis catheters, an observational feasibility study." PLOS ONE 16, no. 3 (March 11, 2021): e0247615. http://dx.doi.org/10.1371/journal.pone.0247615.
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Background Despite advances in immunosuppression and surgical technique, pancreas transplantation is encumbered with a high rate of complication and graft losses. Particularly, venous graft thrombi occur relatively frequently and are rarely detected before the transplant is irreversibly damaged. Methods To detect complications early, when the grafts are potentially salvageable, we placed microdialysis catheters anteriorly and posteriorly to the graft in a cohort of 34 consecutive patients. Glucose, lactate, pyruvate, and glycerol were measured at the bedside every 1–2 hours. Results Nine patients with graft venous thrombosis had significant lactate and lactate–to-pyruvate-ratio increases without concomitant rise in blood glucose or clinical symptoms. The median lactate in these patients was significantly higher in both catheters compared to non-events (n = 15). Out of the nine thrombi, four grafts underwent successful angiographic extraction, one did not require intervention and four grafts were irreversibly damaged and explanted. Four patients with enteric anastomosis leakages had significantly higher glycerol measurements compared to non-events. As with the venous thrombi, lactate and lactate-to-pyruvate ratio were also increased in six patients with graft surrounding hematomas. Conclusions Bedside monitoring with microdialysis catheters is a promising surveillance modality of pancreatic grafts, but differentiating between the various pathologies proves challenging.
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Ghoneim, Mohamed A., Mohamed A. Bakr, Ayman F. Refaie, Ahmed I. Akl, Ahmed A. Shokeir, Ahmed B. Shehab El-Dein, Hesham M. Ammar, Amani M. Ismail, Hussein A. Sheashaa, and Mahmoud A. El-Baz. "Factors Affecting Graft Survival among Patients Receiving Kidneys from Live Donors: A Single-Center Experience." BioMed Research International 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/912413.
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Introduction. The aim of this report is to study the graft and patient survival in a large cohort of recipients with an analysis of factors that may affect the final outcomes.Methods. Between March 1976 and March 2008, 1967 consecutive live-donor renal transplants were carried out. Various variables that may have an impact on patients and/or graft survival were studied in two steps. Initially, a univariate analysis was carried out. Thereafter, significant variables were embedded in a stepwise regression analysis.Results. The overall graft survival was 86.7% and 65.5%, at 5 and 10 years, respectively. The projected half-life for grafts was 17.5 years and for patients was 22 years. Five factors had an independent negative impact on graft survival: donor's age, genetic considerations, the type of primary immunosuppression, number of acute rejection episodes, and total steroid dose during the first 3 months after transplantation.Conclusions. Despite refinements in tissue matching techniques and improvements in immunosuppression protocols, an important proportion of grafts is still lost following living donor kidney transplantation, presumably due to chronic allograft nephropathy.
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Bushell, Andrew, and Kathryn J. Wood. "Permanent survival of organ transplants without immunosuppression: Experimental approaches and possibilities for tolerance induction in clinical transplantation." Expert Reviews in Molecular Medicine 1, no. 17 (October 29, 1999): 1–31. http://dx.doi.org/10.1017/s1462399499001179.
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During the past 30 years, organ transplantation has developed from a highly experimental procedure into an important part of routine clinical practice. This is reflected by the fact that graft survival times, which were once considered in terms of days or weeks, are now measured in terms of years or decades, with enormous corresponding benefits for the patient. Much of this improvement is due to the development of sophisticated immunosuppressive drugs that inhibit the rejection response mediated by the immune system of the recipient. However, almost without exception, all of the grafts that are transplanted from one genetically disparate individual to another are eventually rejected. The Holy Grail in transplantation is the development of protocols that lead to transplantation tolerance and provide stable graft function without long-term drug therapy. In this article, we have discussed the need for alternatives to current immunosuppression and reviewed the results of animal models, which suggest that long-term stable tolerance is an achievable goal.
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Ricordi, Camillo, Norico Murase, Cristiana Rastellini, Roubik Behboo, Anthony J. Demetris, and Thomas E. Starzl. "Indefinite Survival of Rat Islet Allografts following Infusion of Donor Bone Marrow without Cytoablation." Cell Transplantation 5, no. 1 (January 1996): 53–55. http://dx.doi.org/10.1177/096368979600500110.
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We have tested the effect of donor bone marrow cell (DBMC) infusion on the survival of pancreatic islet allografts in the rat, without the use of cytoablative recipient conditioning. Lewis and diabetic Brown Norway rats were used as donors and recipients, respectively. Donor islets were placed beneath the left renal capsule. Infusion of DBMC and temporary immunosuppression followed by delayed islet transplantation resulted in indefinite survival of all islet grafts (MST >180 days). Control animals demonstrated recurrent hyperglycemia (islet allografts rejection). Donor bone marrow derived cells were detected in the spleen and cervical lymph nodes of BN recipients of LEW bone marrow but not in the recipients of islet transplants alone. Second set full thickness skin grafts were performed in normal BN and in recipients of a previously successful ITX. Donor specific skin grafts were accepted in the animals that had received DBMC 40 days before the islet allograft, while animals receiving DBMC at the time of the islet allograft rejected the donor specific skin graft similarly to the controls. However, these animals did not reject a second set donor-specific islet transplant. The results indicate that radiation conditioning of the recipients was not necessary to induce microchimerism and graft acceptance in this rodent model of islet allotransplantation.
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Kozlowska, Urszula, Aleksandra Klimczak, Karolina Anna Bednarowicz, Tomasz Zalewski, Natalia Rozwadowska, Katarzyna Chojnacka, Stefan Jurga, Eytan R. Barnea, and Maciej K. Kurpisz. "Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory?" Cells 10, no. 7 (July 16, 2021): 1804. http://dx.doi.org/10.3390/cells10071804.
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Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, causing motor neuron and skeletal muscle loss and death. One of the promising therapeutic approaches is stem cell graft application into the brain; however, an immune reaction against it creates serious limitations. This study aimed to research the efficiency of glial restricted progenitors (GRPs) grafted into murine CNS (central nervous system) in healthy models and the SOD1G93A ALS disease model. The cellular grafts were administered in semiallogenic and allogeneic settings. To investigate the models of immune reaction against grafted GRPs, we applied three immunosuppressive/immunomodulatory regimens: preimplantation factor (PiF); Tacrolimus; and CTLA-4, MR1 co-stimulatory blockade. We tracked the cells with bioluminescence imaging (BLI) in vivo to study their survival. The immune response character was evaluated with brain tissue assays and multiplex ELISA in serum and cerebrospinal fluid (CSF). The application of immunosuppressive drugs is disputable when considering cellular transplants into the immune-privileged site/brain. However, our data revealed that semiallogenic GRP graft might survive inside murine CNS without the necessity to apply any immunomodulation or immunosuppression, whereas, in the situation of allogeneic mouse setting, the combination of CTLA-4, MR1 blockade can be considered as the best immunosuppressive option.
Dissertations / Theses on the topic "Transplants; Immunosuppression; Grafts"
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Fluck, Nicholas C. "Immunological events resulting from intrathymic delivery of alloantigen." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312492.
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Johns, Rosemary. "The role of nitric oxide and inflammatory cytokines in delayed graft function of DCD renal transplants : the effect of induction immunosuppression." Thesis, Cardiff University, 2018. http://orca.cf.ac.uk/114043/.
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Ischemia Reperfusion Injury (IRI) has a significant influence on patient outcomes after renal transplantation. The role of Nitric Oxide (NO) in IRI is controversial with evidence for both protective and deleterious effects. The aim of this project was to investigate NO in recipients of Donation After Cardiac Death (DCD) renal transplants, who are expected to have high rates of Delayed Graft Function (DGF) as a result of IRI, and to correlate this with their inflammatory response and induction immunosuppression. Methods Plasma samples were collected from 35 recipients of DCD renal transplants around the time of transplantation. NO2- and NO3- were measured using the Griess reaction and Ozone chemiluminescence and cytokines were measured using Luminex. Results At 2 and 8 hours post reperfusion of the transplanted kidney changes in NO2- were associate with the age of the recipient (p = 0.05 and 0.001 respectively) and at 8 hours very strongly related to the warm ischemic time (p < 0.0005). At 8 hours post reperfusion there was a strong negative correlation between the age of the recipient and the change of NO3- (p = 0.002). IL-6 and IL-10 were found to increase significantly at 30 minutes and 2 hours after reperfusion (p < 0.0005). IL-6, IL-10 and TNF-α were all influenced significantly by induction immunosuppression and at 30 minutes post reperfusion changes in NO2- were also affected by the induction. IV Conclusion Changes in NO2- were influenced by factors effecting renal IRI and also by induction immunosuppression. Increasing age was associated with dampening of the NO2- and NO3- response. Cytokines levels rose after reperfusion of the kidney and their changes were modified by induction immunosuppression.
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Prado, Elisângela dos Santos. "Efeito da conversão para sirolimo comparada à manutenção de baixos níveis de inibidores de calcineurina na progressão da nefropatia crônica do enxerto em transplantados renais." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5148/tde-30102008-171610/.
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Introdução: A nefropatia crônica do enxerto permanece sendo a principal causa de perda tardia de enxertos renais. No momento, não existe uma estratégia terapêutica definida para minimizar ou reverter a perda da função renal. Diversas tentativas terapêuticas foram empregadas sem resultados definitivos. As estratégias de minimização de inibidores da calcineurina (CNI) com conversão para Micofenolato mofetil (MMF) e conversão para Sirolimo (SRL) são as mais promissoras. Este estudo avaliou a segurança e a eficácia dessas duas estratégias terapêuticas na progressão da nefropatia crônica do enxerto em pacientes transplantados renais. Métodos: Foram selecionados pacientes com filtração glomerular (RFG) medida por depuração de 51Cr-EDTA entre 25 e 60 ml/min/1,73 m2 que apresentaram alterações histológicas compatíveis com nefropatia crônica do enxerto e que não apresentaram proteinúria 24 h superior a 800 mg/24 h. Os pacientes foram randomizados para serem convertidos ao SRL ou manterem-se sob níveis baixos de CNI associados ao MMF e prednisona. O objetivo primário foi avaliar um objetivo composto pelos seguintes eventos: morte, perda do enxerto, rejeição aguda ou perda de RFG inicial superior a 20%. Os pacientes foram acompanhados por 12 meses e a uma análise por intenção de tratar foi realizada ao fim desse período. Resultados: Vinte e nove pacientes foram randomizados para os grupos SRL (n=14) e CNI (n=15). Não houve diferença entre os grupos quanto a os dados demográficos e imunológicos. Os valores de creatinina sérica e a TFG foram semelhantes no momento da randomização. A sobrevida dos pacientes e dos enxertos foi de 100%. Não foram observados episódios de rejeição aguda. Após 12 meses, não houve diferença significativa entre os grupos com relação à TFG. Houve maior número de eventos adversos não-graves no grupo SRL, destacandose, acne, edema, piora de dislipidemia e anemia. Entretanto, o número de eventos adversos graves não foi estatisticamente diferente entre os grupos. SRL foi descontinuado temporariamente em 1 paciente, mas não ocorreu descontinuação definitiva no estudo. Conclusão: Os dois esquemas terapêuticos apresentaram desempenhos rigorosamente semelhantes com relação à evolução da função renal e quanto à evolução histológica, mas houve um número maior de eventos adversos não-graves com o uso de sirolimoChronic allograft nephropathy is the main cause of late kidney graft loss. Several treatments have been proposed for this condition without conclusive results. Calcineurin inhibitors minimization and conversion to Sirolimus are the most promising alternatives. This study evaluated the safety and the efficacy of these therapeutic strategies on one-year progression of chronic allograft nephropathy in kidney transplant recipients. Patients with measured glomerular filtration rate (51Cr-EDTA plasmatic clearance) between 25 e 60 ml/min/1,73 m2 and histological findings of CAN, with proteinuria less than 800 mg/24 h were included. They were randomized either to Sirolimus or to low-level of CNI (both groups received MMF and prednisone). The primary end-point was a composite of first occurrence of death, graft loss, acute rejection or a 20% decrease of initial GFR. Patients were followed for 12 months and evaluated as intention-to-treat analysis. Twenty-nine patients were included in this study. Fourteen patients were randomized to SRL group and fifteen to CNI group. At baseline, no differences were detected in any of the demographic and immunologic group characteristics. Also, serum creatinine and GFR were not different at randomization. One year after conversion, patient and graft survival was 100%. At 12 months, there were no differences in GFR between two groups, in SRL group was 41,99 ± 13,48 ml/min/1,73 m2and in CNI group was 41,21 ± 9,10 ml/min/1,73 m2 (p=0,96). Non-serious adverse events, like anemia (p=0,006), acne (p=0,006), edema (p=0,005) and mouth ulcers (p=0,017) were more frequently found in the SRL group. No significant difference in serious adverse events was observed. SRL was temporarily interrupted in one patient. None of the patients dropped-out from the study and none required study drug discontinuation. In conclusion both regimens conferred equal beneficial in GFR preservation in CAN patients. However, SRL was associated with more adverse events
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Galvao, Flávio Henrique Ferreira. "Modelo experimental de doença do enxerto versus hospedeiro após transplante de intestino delgado." Universidade de São Paulo, 1998. http://www.teses.usp.br/teses/disponiveis/5/5132/tde-13072011-171433/.
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A doença do enxerto versus hospedeiro (DEVH) é uma grave complicação do transplante de órgãos sólidos, com alta mortalidade. Seu estudo tem sido limitado pela carência de modelos experimentais apropriados. Descreve-se um modelo de DEVH baseado no aumento do quimerismo, sua evolução clínica, histopatológica, do número das células quiméricas, do perfil das citocinas e da tolerância imunológica. Ratos Lewis (LEW) foram submetidos a transplante simultâneo de intestino delgado e medula óssea provenientes de ratos ACI (grupo de estudo - E) ou LEW (grupo controle - C), tratados com FK-506 (1 mg/Kg/dia) entre o 0 e 13o PO, e uma dose semanal daí por diante. Os ratos foram divididos nos seguintes grupos: E1- 6 ratos sacrificados no 120o PO. E2- 8 ratos após apresentarem sinais clínicos graves de DEVH entre o 189o e o 271o PO. Como controle, ratos LEW foram receptores dos mesmos tipos de enxertos provenientes de ratos LEW, submetidos à mesma imunossupressão e foram assim divididos: C1- 6 ratos sacrificados no 120o PO, C2- 5 ratos sacrificados entre o 223o e o 270o PO. A citometria de fluxo foi realizada para quantificar a porcentagem das células linfóides de ACI doadores no sangue periférico nos E1, E2 em 6 períodos: 30o PO, 65o PO, 95o PO, 120o PO, 160o PO, 200o PO. Os animais foram examinados 2 vezes por semana à procura de sinais de DEVH (rash cutâneo, perda de peso, de pelo e hiperqueratose). No sacrifício dos animais do grupo E1 e C1, foram colhidas amostras de língua (LI), de linfonodos cervicais (LC), intestino delgado do receptor e do enxerto para análise das citocinas IL-2, IL-4, IL-6, IL-10, IFN-gama e TNF-alfa por meio da reação em cadeia da polimerase. Em todos os grupos foram também colhidas amostras destes órgãos para histopatologia e nos animais do grupo E2 linfonodos cervicais foram processados para análise da reatividade celular por meio da reação mista dos linfócitos (MLR). A evolução clínica e histopatológica foi graduada de 0 a 3 de acordo com a severidade dos sintomas e do infiltrado mononuclear das amostras. Os ratos dos grupos E1 e E2 iniciaram sinais da DEVH entre o 84o e 115o PO. Os ratos dos grupos C1 e C2 não apresentaram evidência de DEVH. Amostras de LI e LC dos ratos do grupo E1 apresentaram alterações histopatológicas grau 2 e do grupo E2 apresentaram alterações histopatológicas grau 3, respectivamente. Nenhuma alteração histopatológica foi encontrada nos ratos do grupo controle e em amostras do ID. Nenhuma alteração histopatológica foi encontrada no intestino delgado do receptor e do enxerto. O aumento da porcentagem de células do doador no sangue periférico do receptor foi progressivo chegando a 5,4±2.3% no 10o período, 21±4,6% no 3o período e 39,3±4% no 6o período. IL-2, IL-6, IL-10, IFN-gma e TNF-alfa estiveram aumentados em língua e IL-4, IL-6, IL-10, IFN-gama e TNF-alfa em linfonodos cervicais. Os linfócitos de ratos do grupo E2 mostraram hiporreatividade aos de ratos ACI e hiperreatividade aos de ratos PVG (terceira parte) denotando tolerância imunológica. Neste modelo experimental há uma inexorável evolução imunológica para DEVH; existe correlação direta entre o aumento do quimerismo em sangue periférico e da expressão de citocinas em língua e linfonodos cervicais e a severidade da DEVH, além da indução de tolerância imunológica do rato do grupo E2 quimérico ao rato ACI normal.Graft-versus-host disease (GVHD) has been a major concern after small bowel transplantation (SBTX) and the lack of suitable experimental models has limited the study of GVHD after solid organ transplantation. Here we describe a re1evant experimental model of GVHD after fully allogeneic SBTX based on chimerism augmentation, its clinical and histophatological evolution, cytokine involvement, responsible donor cell and immunologic tolerance analysis. LEW rat recipients received orthotopic SBTX and simultaneous donor bone marrow cell infusion (250x106), from ACI rats (experimental group - E) or LEW (control group C). FK-506 was administered dayly at a dose of 1 mg/kg on day 0 to 13, then continued as a weekly injection of same dose until the experimental end point. The recipients were divided in the following groups: E1 - 6 rats sacrificed at 120° POD. E2 - 8 rats sacrificed with critical GVHD between DPO 189 to 271. LEW recipient of LEW grafts, under the same immunossupression were used as control and divided as: C1 - 6 rats sacrificed at POD 120; C2- 5 rats sacrificed between 223 and 270 POD the number of donor cell in the recipient circulation was determined by flowcytometry in 6 pos-operative time: 30, 65, 95, 120, 160, 200. The rats were analyzed twice a week for body weigh and searching for signs of GVHD (cutaneous rush, hiperkeratosis and loss of hair and body weigh). At the sacrificed, samples from tongue (TG), cervical lymph node (CLN), donor (SBD) and recipient (SBR) small bowel were taken from all animals for histophatology and from E1 and C1l animals for IL-2, IL-4, IL-6, IL-10, IFN-gama e TNF-alfa cytokines analysis using reverse transcription polymerase chain reaction. Samples from cervical lynph nodes of 5 animals from group E2 were used for mixed lymphocyte reaction for tolerance analysis. The clinical and histophatological evolution of the disease were evaluated from degree 0 to 3 according to the severity. GVHD in E1 and E2 animals started between 84 and 115 POD. Histophatological analysis of TG and CLN showed that E1 animals present GVHD grade 2 and E2 animals grade 3. The increase of donors cells in the recipient circulation was progressive and account for 5.4± 2.3% at POD 30, 21.4±4.6% at POD 95 and 39.3±4% at POD 200. IL-4, IL-6, IL-10, IFN-gama e TNF-alfa were upregulated in CLN and IL-2, IL-6, IL-10, IFN-gama e TNF-alfa were upregulated in TG when compared with the respective controls. The lymphocytes from E2 group showed hyporeactivety to lymphocytes of normal ACI and hypereactivety to those of PVG, meaning tolerance. No cytokines alteration was noted in SBD neither SBR. Animals from group C1 and C2 did not present any sign of disease. This result show that GVHD is a inexoravel evolution under the experimental conditions of this study and the evolution of the disease is near correlated with the augmentation of the donor cells in the recipient circulation and upregulation of cytokines gene expression in target organs. Tolerance to the same donor strain lynphocytes was also noted.
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Barbieri, Lucas Regatieri. "Uso de nanoemulsões lipídicas como veículos de paclitaxel e de metotrexato no tratamento da doença vascular do coração transplantado em coelhos." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5156/tde-24102016-162520/.
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Introdução: A doença vascular do coração transplantado, consiste em um processo inflamatório proliferativo que compromete o sucesso a longo prazo do transplante cardíaco e não há prevenção ou tratamentos efetivos. Uma nanoemulsão lipídica (LDE) pode carregar agentes quimioterápicos na circulação e concentrá-los nos enxertos cardíacos dos coelhos. O objetivo deste estudo foi investigar os efeitos do paclitaxel combinado a LDE;do metotrexate combinado ao LDE e a associação de ambos quimioterápicos ao LDE nos corações transplantados. Método: 28 coelhos alimentados com dieta com teor de 0,5% de colesterol e submetidos a transplante cardíaco herotópico foram tratados com ciclosporina (dose 10 mg/kg/ dia por via oral) e alocados em 4 grupos de 7 animais.Um grupo recebeu a associação de Metotrexate e LDE endovenosa (4 mg/kg/semana); segundo grupo recebeu por via endovenosa a combinação de Paclitaxel e LDE; o terceiro grupo recebeu a associação de LDE com metotrexate e paclitaxel; grupo controle que recebeu somente solução salina intravenosa. Os animais foram sacrificados 6 semanas após o procedimento. Foram realizadas análises da morfologia,histologia,imunohistoquímica e análise da expressão gênica do enxerto e dos corações nativos. Resultado: Em comparação com o grupo controle,coelhos transplantados e tratados com paclitaxel associado ao LDE apresentaram redução em 50% de estenose em artérias coronárias. Já nos grupos que usaram metotrexate associado a LDE ou paclitaxel combinado com metotrexate e associado a LDE, houve redução em 18% da estenose coronariana em relação ao grupo controle,mas a diferença não apresentou significância estatística.Nos três grupos tratados, houve redução do infiltrado macrofágico. No grupo que recebeu metotrexate associado a LDE,a expressão gênica de fatores pró-inflamatórios( TNF-alfa; MCP1; IL 18; VCAM-1 e MMP-12) foi reduzida drasticamente; enquanto a expressão de agentes anti-inflamatórios(IL 10 por exemplo) aumentou. Nos outros dois grupos (LDE+paclitaxel e LDE+paclitaxel e metotrexate) não houve influência consistente na expressão de genes pró e anti-inflamatórios. Conclusão: A associação paclitaxel e LDE promoveu melhora importante na vasculopatia dos enxertos.A associação metotrexate e LDE e a metotrexate mais palcitaxel e LDE reduziram a estenose de coronárias porém sem significância estatística. O infiltrado macrofagocítico foi reduzido nos três grupos tratados. Tais resultados podem servir de ponte para novos ensaios clínicosBackground: Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and currently has no effective prevention and treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agentsin the circulation and concentrates them in the heart graft in rabbits. The aim of this study was to investigate the effects of paclitaxel (PACLI) binded tire parentesis to LDE, methotrexate (MTX) binded to LDE and the association of both particles in transplanted heart. Methods: Twenty eight rabbits fed 0,5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10mg/kg/daily orally) and allocated to four groups of 7 animals. One group was treated with intravenous LDE-MTX (4mg/kg B.W., weekly); a second with LDE-paclitaxel, the third one with association of LDE-PACLI with LDE-MTX and the control group received only weekly intravenous saline solution. Animals were sacrificed 6 weeks later for morphometric, histological, immunohistochemical and gene expression analysis of the graft and native hearts. Results: Compared to controls, grafts of LDE-PACLI treated rabbits showed 50%reduction of coronary stenosis and in the LDE-MTX and LDE-MTX/PACLIstenosiswas around 18% less than control but this difference was not statistically significant. In the 3 treatment groups macrophage infiltration was decreased. In LDE-MTX group, gene expression of pro-inflammatory factors TNF-?, MCP-1, IL-18 and VCAM-1, and MMP-12 was strongly diminished whereas expression of anti-inflammatory IL-10 increased. In the other two treatment, groups (LDE-PACLI and LDE-PACLI/MTX) there was not a consistent influence in pro and anti-inflammatory gene expression. Conclusions: LDE-PACLI promoted strong improvement of the cardiac allograft vasculopathy. LDE- MTX and LDE -MTX/PACLI decreased coronary stenosis but without statistic significance. Macrophage infiltration was decrease in the three treatment groups. This new preparation maybe candidate for future clinical trials
Books on the topic "Transplants; Immunosuppression; Grafts"
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Oremus, Mark. Utility of monitoring mycophenolic acid in solid organ transplant patients. Rockville, MD: Agency for Healthcare Research and Quality, 2008.
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Nessralla, Laurie-Ann. Incidence of rejection, morbidity, mortality and graft function in renal transplant recipients following cyclosporine to azathioprine switch. [New Haven: s.n.], 1990.
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Retter, Andrew. Management of the bone marrow transplant recipient in ICU. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0375.
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Bone marrow transplants are an exciting and rapidly evolving area of haematology providing life-saving therapy to many patients and the number performed annually is increasing. Transplants are generally not considered as first line therapy due to their inherent toxicity and high rate of complications. The patients tend to have more heavily pre-treated disease with it attendant toxicities and a decreased physiological reserve. Admission rates vary between series from 15 to 30%. It is increasingly important that intensivists are aware of the basic principles of bone marrow transplantation and its’ possible morbidities. There are two types of transplant autologous transplants, where the patient’s own stem cells are returned to them and transplants from a donor. Only allogeneic transplants are associated with graft-versus-host disease. Allograft recipients also require immunosuppression to prevent transplant rejection. It is essential that this immunosuppression is continued when patients are admitted to intensive care. Transplant patients are always severely immunocompromised and prone to prolonged periods of neutropenia. They routinely receive antiviral, antifungal, and antibacterial prophylaxis, which must be continued on their admission. They remain vulnerable to unusual infections presenting in an atypical fashion. It is essential to have both a very low clinical threshold of suspicion for infection and detailed local protocols established to guide empirical antimicrobial therapy. Although traditionally poor, the prognosis is slowly improving.
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Barrett, Jessica, and Martin Carby. Transplant. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199657742.003.0021.
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Since the first successful lung transplant in 1981, tens of thousands of operations have been performed across the world. Yet despite significant technical advances, mortality is the highest of any solid organ transplant. Most patients will have a major complication within the first 5 years of the operation. These are best managed in transplant centres. However, a working knowledge of the presentation and initial management is essential for a respiratory physician. Although the rate of complications remains high, more than 80% of patients with surviving transplants report no limitation of activity at 1, 3, and 5 years. Developments in surgical technique have reduced immediate complications, and immunosuppressive regimens continue to improve. However, the incidence of obliterative bronchiolitis remains high and is responsible for the majority of graft failures.
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Gruenewald, Simon, and Philip Vladica. Renal transplant imaging. Edited by Jeremy R. Chapman. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0282.
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The purpose of imaging of the transplant kidney is to assess integrity, anatomy, and function. Relatively or actually non-invasive technologies can be used to monitor for potential early post-transplant complications such as acute tubular necrosis, acute rejection, haematoma, pyelonephritis, abscess, urinoma, ureteral obstruction, vascular complications, and rarely graft torsion. The technologies also assist in the diagnosis and management of late complications such as those arising from immunosuppression, chronic rejection, lymphocoele, cyst, renal artery stenosis, urinary obstruction, and tumours. This chapter demonstrates the capacity of the various imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging, to assist in the clinical management of the renal transplant recipient.
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Melville, Williams G., Burdick James F. 1941-, and Solez Kim 1946-, eds. Kidney transplant rejection: Diagnosis and treatment. New York: M. Dekker, 1986.
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1968-, Oremus Mark, Zeidler Johannes, and United States. Agency for Healthcare Research and Quality., eds. Utility of monitoring mycophenolic acid in solid organ transplant patients. Rockville, MD: Agency for Healthcare Research and Quality, 2008.
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1968-, Oremus Mark, Zeidler Johannes, and United States. Agency for Healthcare Research and Quality., eds. Utility of monitoring mycophenolic acid in solid organ transplant patients. Rockville, MD: Agency for Healthcare Research and Quality, 2008.
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Utility of monitoring mycophenolic acid in solid organ transplant patients. Rockville, MD: Agency for Healthcare Research and Quality, 2008.
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Knight, Simon R., and Rutger J. Ploeg. Immediate post-transplant care and surgical complications. Edited by Jeremy R. Chapman. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0280_update_001.
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Care of the post-transplant kidney patient is complex and requires multidisciplinary team working. Careful attention is paid to haemodynamics, fluid balance, microbiology, drug prescription, and patient instruction. Delays in, or reduction of, graft function should be investigated and treated immediately to ensure long-term graft survival. Because complications do occur, they must be recognized early and dealt with promptly. The nature of the transplant operation and the need for immunosuppression mean that the complications differ from those of ordinary general surgical patients, and so require specialist medical, microbiological, or radiological input with a narrower time window for correction. This chapter covers the immediate postoperative care of the renal transplant recipient both as an inpatient and the early period as an outpatient, highlighting the potential complications and their management.
Book chapters on the topic "Transplants; Immunosuppression; Grafts"
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Lang, Ph, V. Bierre, C. Baron, S. Cholin, G. Rostoker, and B. Weil. "Absence of correlation between graft-versus-host associated immunosuppression and cytotoxic T cell activity in response to major histocompatibility antigens." In Transplant International Official Journal of the European Society for Organ Transplantation, 681–83. Berlin, Heidelberg: Springer Berlin Heidelberg, 1992. http://dx.doi.org/10.1007/978-3-642-77423-2_200.
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Torpey, Nicholas, and John D. Firth. "Renal transplantation." In Oxford Textbook of Medicine, edited by John D. Firth, 4879–908. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0481.
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Renal transplantation is the preferred option for the treatment of endstage chronic renal failure in patients for whom there are no major medical contraindications. In well-selected recipients, both life expectancy and quality of life are superior to treatment with long-term dialysis. However, as the dialysis population continues to grow, the gap between supply and demand for renal transplantation is widening. Immunosuppression—excepting for transplants between HLA-identical twins, immunosuppression is required to prevent rejection, but there is no clear consensus on the best immunosuppressive regimen. Most centres use an induction antibody directed against CD25 or a T-lymphocyte-depleting antibody (thymoglobulin or alemtuzumab), followed by what is now called standard triple therapy—comprising a calcineurin inhibitor (almost always tacrolimus), combined with either mycophenolate mofetil or azathioprine, and steroids. Steroids are not infrequently tailed off rapidly in the early post-transplant period. Transplant rejection can be classified into four main categories: (1) hyperacute, (2) accelerated, (3) acute cellular, and (4) humoral. Complications of renal transplantation—this chapter discusses specific and nonspecific side effects of immunosuppressive agents, infective complications (including viral, bacterial, fungal, and parasitic infections), malignant complications, and other complications (including hypertension, accelerated atherosclerosis, and electrolyte, musculoskeletal, haematological, gastrointestinal, and cosmetic disorders) in detail. Prognosis—first-year transplant losses from rejection have been dramatically reduced from about 40% in the 1970s to 5%. However, the rate of chronic graft loss remains at about 4% per year. The commonest cause of insidious late graft failure is probably chronic antibody-mediated rejection, frequently associated with poor adherence to immunosuppression. Calcineurin toxicity may also contribute. A major focus of research is to identify non-nephrotoxic immunosuppressive agents able to suppress antibody-mediated rejection.
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Naik, Seema, Kevin Rakszawski, Joseph Cioccio, Hong Zheng, and Hiroko Shike. "Immunosuppression and Viral Infections." In Immunosuppression. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.91954.
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Immunosuppression is commonly used for prevention of graft rejection in solid organ transplantation (SOT) and prevention of graft versus host disease in hematopoietic allogeneic stem cell transplant (ASCT). In ASCT, immunosuppression is used to control GVHD and can be tapered off within 6–12 months after transplantation. SOT recipients require lifelong immunosuppression to prevent graft rejection, making them susceptible to serious viral infections including EBV PTLD. EBV PTLD occurs within the first 6 months following ASCT prior to effective reconstitution of cytotoxic T lymphocytes (CTL). Our understanding on EBV-related PTLD is mostly extrapolated from SOT-associated PTLD. Features of conditioning and use of serotherapy remain important in development of EBV PTLD. Other viral infections that occur early post-transplant include CMV, HHV6, BK, and adenovirus, and usually correspond to degree of immunosuppression post-transplant. These infections are associated with significant morbidity and mortality. However, the current literature lacks information on outcomes of viral infections related to immunosuppression. Alternative donor ASCT are now more common, and patients are more susceptible to multiple viral infectious complications at the peak of immunosuppression and require monitoring for viral infections in these immunosuppressed patients.
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Razonable, Raymund R. "Infections in Transplant Recipients." In Mayo Clinic Infectious Diseases Board Review, 443–57. Oxford University Press, 2012. http://dx.doi.org/10.1093/med/9780199827626.003.0039.
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Infections are the most common complication of organ transplant. They are caused by bacteria, fungi, viruses, and parasites. Transplant-associated infections usually fall into one of several categories: nosocomial or health care–associated pathogens (Staphylococcus aureus, enterococci, Pseudomonas aeruginosa, and others), opportunistic pathogens (cytomegalovirus, Aspergillus fumigatus, Pneumocystis jiroveci, polyomaviruses BK virus and JC virus, and others), and community-acquired pathogens (Streptococcus pneumoniae and respiratory viruses). Determinants of risk of infection after transplant include epidemiologic exposures (exposure history for both donor and recipient) and net state of immunosuppression (including antirejection immunosuppressive drugs, graft-vs-host disease prophylaxis and treatment, cytotoxic chemotherapy, immunomodulating viruses, and inherent defects in innate and adaptive immunity). Diagnosis and treatment of various types of infections are reviewed.
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Paul, Riley, and John O’Grady. "Diabetes mellitus and transplantation." In Oxford Textbook of Endocrinology and Diabetes, 2019–23. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199235292.003.1599.
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Diabetes mellitus is a common and significant complication of solid organ transplantation, affecting approximately 20% of transplant recipients (1). However, reported incidences vary widely due to a combination of varying historical definitions, whether diabetes is transient or sustained, and the profile of risk factors, including the immunosuppressive regimens used. The development of the entity of ‘new-onset diabetes after transplantation’ (NODAT) is gaining attention, as it can be associated with early microvascular complications (2) and an increase in cardiovascular risk (3–5). Cardiovascular disease is the most common cause of post-transplant death in some series (6). NODAT is also associated with an increased risk of infection, graft failure, and patient mortality (1, 3, 4, 7, 8). NODAT and pre-existing diabetes mellitus have also been associated with more aggressive disease recurrence after liver transplantation, particularly of hepatitis C (9). Because of the above, considerable effort has been focused on identifying and reducing an individual’s risk of NODAT; establishing effective screening to allow early diagnosis and early intervention to prevent or delay the development of severe complications. In addition, the increased flexibility in immunosuppression regimens as a consequence of the wider range of drugs available is allowing the individualization of therapy that may be directed at reducing the risk of NODAT. The wide ranges quoted for the incidence of NODAT preclude meaningful comparison between the different solid organs. However, liver transplantation is notable because of the very high incidence of transient impairment of glycaemic control immediately after implantation of the graft (resistant hyperglycaemia may be an indicator of poor early function), which is not considered to represent NODAT unless it persists beyond 2 weeks after transplantation. In addition, some people with pre-existing diabetes receiving liver transplants buck the trend and exhibit significant reductions in insulin requirements after liver transplantation, presumably due to increased tissue sensitivity.
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N. Mohite, Prashant, Kavita Dave, Anna Reed, and André R. Simon. "Lung Transplantation in Patients with Cystic Fibrosis." In Cystic Fibrosis - Facts, Management and Advances. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.94523.
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Cystic fibrosis (CF) is one of the most common indications for lung transplant (LTx) and nearly one-third of the LTx worldwide are performed in people with CF (PwCF). Due to vast developments in diagnostic modalities, antibiotic therapies, and management of associated comorbidities in dedicated and experienced centres, over the past few decades, more PwCF are reaching adulthood than ever before. This has increased the burden on transplant programs particularly in a universal donor shortage scenario. To improve the donor pool a diligent and proactive donor care management, acceptance of marginal organs and utilisation of ex-vivo lung perfusion systems for organ preservation, assessment, and improvement is being advocated widely. LTx is not a readily available therapy and the average waiting time is 18 months in the UK. Therefore, it is essential that PwCF are referred for LTx assessment when their disease is stable, before respiratory deterioration leads to overall deconditioning of the patients. Once listed for LTx, it is crucial to control waiting list mortality by prioritising rapidly deteriorating patients through schemes like the lung allocation score, national urgent and super-urgent waiting lists, and institutional highlighting of deteriorating patients that do not meet other urgent criteria. LTx in PwCF is challenging due to colonisation of the respiratory tract with multi-drug resistant organisms, associated comorbidities such as diabetes, liver disease, gastro-oesophageal reflux, and distal intestinal obstruction syndrome (DIOS) and CF-specific technical difficulties (adhesions due to prior pneumothoraces or pleurodesis, or bronchial collaterals that increase surgical time). Hilar lymphadenopathy and bronchial collaterals may increase surgical time, organ ischemia time, intra and post-operative bleeding, and blood transfusions. Advances in immunosuppression, prophylactic anti-viral and anti-fungal therapies, early ambulation and rigorous physiotherapy, and meticulous postoperative follow up with spirometry, x-rays, and bronchoscopies to detect rejection at the early stage followed by its efficient treatment have helped to improve post-LTx survival in the CF patients. Constant development in the surgical field with adoption of off-pump transplantation, sternal sparing bilateral thoracotomy approach, and utilisation of mechanical circulatory assist as a bridge to transplant and as a support for primary graft failure strives for better outcomes. However, chronic lung allograft dysfunction, chronic refractory infections, malignancies, and CF associated comorbidities remain major determinants of post-LTx long term survival. Despite this, CF patients are often good candidates for re-do LTx with improving survival outcomes. In this chapter, we are compiling the different aspects of LTx in PwCF emphasising the advances in bridge to transplantation, the surgical approach, management of primary graft failure, and immunosuppression as well as complications post-transplant.
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Marsh, Judith C. W., Shreyans Gandhi, and Ghulam J. Mufti. "Acquired aplastic anaemia and pure red cell aplasia." In Oxford Textbook of Medicine, edited by Chris Hatton and Deborah Hay, 5336–48. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0529.
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Aplastic anaemia (AA) is a rare bone marrow failure (BMF) disorder characterized by pancytopenia and a hypocellular bone marrow. AA is commonly acquired, immune mediated, and idiopathic in nature. Activated autoreactive, cytotoxic CD8+ T cells are present but recent work has shown that CD4+ T cells appear to be more important in the pathogenesis of acquired AA. The immune nature of acquired AA provides the rationale for one of the treatment options, namely immunosuppressive therapy. First-line treatment of acquired AA is either immunosuppressive therapy with antithymocyte globulin and ciclosporin or allogeneic haematopoietic stem cell transplantation (HSCT). Both modalities offer excellent survival. Patients treated with immunosuppressive therapy are at later risk of relapse and clonal evolution to myelodysplastic syndrome and acute myeloid leukaemia, so require long-term follow-up. HSCT, if successful, is curative, but risks include graft rejection, infections, and graft-versus-host disease (GVHD); recent changes to the transplant conditioning regimen have reduced the GVHD risk. The inherited forms of AA include Fanconi’s anaemia, a disorder of DNA repair, dyskeratosis congenita, a disorder of telomere maintenance, and Shwachman–Diamond syndrome, one of the so-called ribosomopathies characterized by defective ribosomal biogenesis. Pure red cell aplasia (PRCA) is a form of BMF characterized by severe anaemia with reticulocytopenia and reduced erythroid progenitors in the bone marrow. PRCA most commonly is an acquired disorder and immune mediated, and often occurs in association with a wide range of conditions. Diamond–Blackfan anaemia, an inherited form of PRCA, is another example of a ribosomopathy, and is caused by mutations in one of many ribosomal protein genes, resulting in haploinsufficiency.
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"Rashes associated with transplantations." In Paediatric Dermatology, edited by Sue Lewis-Jones and Ruth Murphy, 535–38. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198821304.003.0039.
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Dermatological manifestations following transplantation are common but important to recognize and diagnose since they may be severe and life-threatening if not adequately and promptly treated. This chapter provides a systematic overview of the types of skin disease that may be encountered in children that have received a haematological or solid organ transplant. Complications relating to immunosuppression include an increased susceptibility to bacterial, viral, and fungal infections which may be significantly more virulent and hazardous in the context of reduced host immunity. Immune suppressant drugs may also cause drug rashes and aesthetic complications such as acne, hypertrichosis, or gingival hypertrophy, as well as longer-term risks from the development of malignancy. It is also important to recognize the range of mucocutaneous signs of acute and chronic graft versus host disease following bone marrow and solid organ transplantation which, again, may be severe and associated with significant morbidity and mortality.
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Williams, David. "Renal disease in pregnancy." In Oxford Textbook of Obstetrics and Gynaecology, edited by Sabaratnam Arulkumaran, William Ledger, Lynette Denny, and Stergios Doumouchtsis, 170–85. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198766360.003.0014.
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The kidneys undergo marked physiological changes during healthy pregnancy. Awareness of these gestational changes is critical to the management of kidney disease in pregnancy as they both mask and mimic renal disease. Gestational changes to maternal vasculature, clotting, and metabolism predispose previously healthy women to a unique set of acute kidney injuries during pregnancy, whereas women with chronic kidney disease make suboptimal gestational adaptations to pregnancy, with an increased risk of adverse pregnancy outcome and possible further damage to their kidneys. Women with kidney transplants can be confident about the safety of established immunosuppressive regimens during pregnancy and can expect a good pregnancy outcome dictated by the function of their renal graft. Pregnancy outcomes for women on renal replacement therapy have improved through intensive haemodialysis regimens that mimic gestational physiological change. This chapter describes renal physiological change and the management of acute and chronic renal disease in pregnancy.
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"Renal transplantation." In Oxford Desk Reference Nephrology, edited by Jonathan Barratt, Peter Topham, Sue Carr, Mustafa Arici, and Adrian Liew, 689–740. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198777182.003.0015.
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Kidney transplantation is the optimal treatment for end stage renal disease. However, there are risks both from early complications directly related to the surgical procedure, and from longer-term complications resulting from the effects of immunosuppression. This chapter describes the transplant process from the evaluation of patients with renal failure for suitability for transplantation, through the surgical procedure itself, the early and late management of recipients, and the management of the complications that can arise, including acute and chronic graft dysfunction, infection, malignancy, and cardiovascular disease. It also covers the short- and long-term outcomes of kidney transplantation. Since live kidney donors have become an increasingly important source of kidneys for renal transplantation, it also describes the work-up process for potential live donors and the long-term outcomes following donation. Finally, combined kidney/pancreas transplantation is included separately and includes a discussion around the selection and evaluation recipients, the surgical procedure, short- and long-term complications, and the outcomes.
Conference papers on the topic "Transplants; Immunosuppression; Grafts"
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Bai, Xue-peng, Shi-ying Zheng, Dong Jiang, and Hong Li. "Tolerance of Transplanted Xenogeneic Tumour Cell Graft by Fas-Mediated Immunosuppression." In 2010 4th International Conference on Bioinformatics and Biomedical Engineering (iCBBE). IEEE, 2010. http://dx.doi.org/10.1109/icbbe.2010.5515875.
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Huser, B., B. Lämmle, T. H. Tran, M. J. Mihatsch, G. Thiel, and F. Duckert. "FACTOR VIII:C (F VIII:C) AND VON WILLEBRAND FACTOR ANTIGEN (vWFag) IN RENAL TRANSPLANT RECIPIENTS IMMUNOSUPPRESSED WITH CYCLOSPORIN A (CyA)." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644124.
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In 17 consecutive cadaveric kidney transplant recipients F VIII:C and vWFag were repeatedly determined before transplantation and during 4 months thereafter. Graft biopsy was performed in 12 patients for deterioration of renal function. F VIII:C was determined by a one stage clotting assay using F VIII:C deficient substrate plasma. vWFag was assayed by electroimmunoassay using specific rabbit anti-human vWFag antibodies. Results of F VIII:C and vWFag are expressed referring to NHP as 100%.Results: 2/17 patients lost their graft due to irreversible vascular rejection, 2/17 patients had reversible vascular rejection, 2/17 patients developped glomerulonephritis, 6/17 patients showed acute or chronic CyA nephrotoxicity. In 5/17 patients graft biopsy was not necessary. Despite normalisation of renal function (serum creatinine levels<150umol/L) in 9 out of 17 patients F VIII:C (239 ± 66% to 408 ± 74%, mean ± SD) remained elevated in all 17 patients. vWFag (181 ± 29% to 454 ± 84%) was normalised in only 2 out of 17 patients. CyA dosis and CyA blood levels were not correlated with F VIII:C and vWFag. All 4 patients with histological vascular rejection, both patients with later developping glomerulonephritis and 3 out of 6 patients with later developping CyA nephrotoxicity showed F VIII:C/vWFag quotients > 1 (1,1 to 1,3) Four out of 5 patients with well functioning graft had F VIII:C/ vWFag quotients consistently <1 (0,68 to 0,92).Conclusion: 1. The elevated F VIII:C and vWFag levels in chronic renal failure are not normalised during 4 months of observation despite normalisation of renal function by transplantation and immunosuppression with CyA.2. A quotient F VIII :C/vWFag < 1 may indicate a good prognosis for kidney allograft function in the absence of CyA nephrotoxicity whereas later developping graft rejection or glomerulonephritis were associated with F VIII:C/vWFag>1.
Reports on the topic "Transplants; Immunosuppression; Grafts"
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Pelletier, Joseph P., Oluwole Fadare, and Yanyun Wu. Post-Renal Transplant Thrombotic Thrombocytopenic Purpura (TTP): Attributable to Immunosuppression or Graft Rejection? Report of Three Cases and Literature Review. Fort Belvoir, VA: Defense Technical Information Center, January 2005. http://dx.doi.org/10.21236/ada429608.
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