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1
Zdanowski, Zbigniew. "Synthetic vascular graft infection an experimental study with special reference to host mechanisms affecting bacterial graft colonization /". Lund : Dept. of Surgery, Lund University, 1993. http://catalog.hathitrust.org/api/volumes/oclc/39798633.html.
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Usui, Akihiko. "SURGICAL MANAGEMENT OF INFECTED THORACIC ANEURYSMS". Nagoya University School of Medicine, 2013. http://hdl.handle.net/2237/18465.
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Musil, Ian, Vanessa Jensen, Jolyon Schilling, Boyd Ashdown y Tyler Kent. "Enterobacter cloacae infection of an expanded polytetrafluoroethylene femoral-popliteal bypass graft: a case report". BioMed Central, 2010. http://hdl.handle.net/10150/610188.
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INTRODUCTION:Enterobacter cloacae infections are common among burn victims, immunocompromised patients, and patients with malignancy. Most commonly these infections are manifested as nosocomial urinary tract or pulmonary infections. Nosocomial outbreaks have also been associated with colonization of certain surgical equipment and operative cleaning solutions. Infections of an aortobifemoral prosthesis, an aortic graft, and arteriovenous fistulae are noted in the literature. To our knowledge, this is the first isolated account of an E. cloacae infection of a femoral-popliteal expanded polytetrafluoroethylene bypass graft.CASE PRESENTATION:A 68-year-old Caucasian man presented with fever and rest pain in the right lower extremity five months after the placement of a vascular expanded polytetrafluoroethylene graft for femoral-popliteal bypass. Computed tomography angiography demonstrated peri-graft fluid that was aspirated percutaneously with image guidance and cultured to reveal E. cloacae. The graft was revised and then removed. The patient completed a six-week course of ceftazidime and is currently without signs of infection. There were no other reports of E. cloacae graft infections in any patients receiving treatment in the same surgical suite within a month of this report.CONCLUSION:Isolated cases of E. cloacae infection of surgical bypass grafts are rare (unique in this setting). Clinicians should have a high index of suspicion for device contamination in such cases and should consider testing for possible microbial reservoirs. Graft removal is required due to the formation of biofilm and the recent emergence of Enterobacteriaceae producing extended-spectrum beta-lactamase in community acquired infections.
4
Swenne, Christine Leo. "Wound Infection Following Coronary Artery Bypass Graft Surgery : Risk Factors and the Experiences of Patients". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7168.
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Morishima, Manabu. "Sustained release of vancomycin from a new biodegradable glue to prevent methicillin-resistant Staphylococcus aureus graft infection". Kyoto University, 2013. http://hdl.handle.net/2433/180460.
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Manabu Morishima, Akira Marui, Shigeki Yanagi, Takamasa Nomura, Naoki Nakajima, Suong-Hyu Hyon, Tadashi Ikeda, and Ryuzo Sakata. Sustained release of vancomycin from a new biodegradable glue to prevent methicillin-resistant Staphylococcus aureus graft infection. Interact CardioVasc Thorac Surg (2010) 11(1): 52-55 doi:10.1510/icvts.2010.232447Kyoto University (京都大学)
0048
新制・課程博士
博士(医学)
甲第17856号
医博第3825号
新制||医||1000(附属図書館)
30676
京都大学大学院医学研究科医学専攻
(主査)教授 一山 智, 教授 伊達 洋至, 教授 鈴木 茂彦
学位規則第4条第1項該当
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Makabe, Kenichi. "Mycoplasma ocular infection in subretinal graft transplantation of iPS cells-derived retinal pigment epithelial cells". Kyoto University, 2019. http://hdl.handle.net/2433/243304.
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Massicotte-Azarniouch, David. "The Risks Associated with Blood Transfusion in Kidney Transplant Patients: A Retrospective Cohort Study Using Routinely Collected Data". Thesis, Université d'Ottawa / University of Ottawa, 2020. http://hdl.handle.net/10393/40651.
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A blood transfusion may have important immunomodulatory effects and may carry certain risks which could be detrimental to the kidney transplant patient. The aim of this project is to examine the potential risks associated with post-transplant blood transfusions in kidney transplant recipients. We carried out a retrospective cohort study of all adult kidney transplant recipients at The Ottawa Hospital from 2002 to 2018 inclusive. We examined the risks for kidney transplant rejection, graft loss, death, infections and venous thromboembolic events (VTE) associated with the receipt of red blood cell transfusions (RBCTs) administered after kidney transplant. We calculated hazard ratios (HR) using Cox proportional hazards model with RBCT as a cumulative, time-varying exposure. Out of a total study population of 1,258 kidney transplants recipients, 37% received at least one RBCT. The receipt of a RBCT was not significantly associated with the risk for rejection, however it was associated with an increased risk for graft loss, death, infection and VTE. Important biases such as reverse causation and unmeasured confounding may account for some of these findings. That being said, our findings suggest clinicians should be judicious in their use of RBCT in kidney transplant patients.
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Sakaguchi, Hisashi. "Less-invasive and highly effective method for preventing methicillin-resistant Staphylococcus aureus graft infection by local sustained release of vancomycin". Kyoto University, 2008. http://hdl.handle.net/2433/135843.
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Owens, Megan M. (Megan Mary) 1976. "Preliminary design of an implantable boisensor for the detection and differentiation of acute rejection, vascular occlusion, and infection in the liver or kidney transplant graft". Thesis, Massachusetts Institute of Technology, 2000. http://hdl.handle.net/1721.1/89283.
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Bokums, Kristaps [Verfasser] y Johannes [Akademischer Betreuer] Hoffmann. "Irrigation suction drainage and negative pressure wound therapy of lower extremity vascular graft infection in ileofemoral region : clinical and economical aspects / Kristaps Bokums ; Betreuer: Johannes Hoffmann". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1163534188/34.
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Bringhenti, Rafael Nazario. "Linfangiogênese no transplante renal: análise clínico-patológica e imunofenotípica de biópsias de aloenxertos renais de doadores falecidos". Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5144/tde-04082014-111126/.
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INTRODUÇÃO: O papel da linfangiogênese no transplante renal em humanos é desconhecido até o momento. As poucas publicações disponíveis acerca do assunto revelam resultados controversos. O presente estudo visa a avaliar a influência dos vasos linfáticos sobre aspectos clínicos e patológicos no transplante renal. MÉTODOS: Biópsias de indicação clínica de pacientes submetidos a transplante renal com enxertos oriundos de doadores falecidos na Unidade de Transplante Renal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo de janeiro de 2007 a dezembro de 2009 foram selecionadas e os dados clínicos destes pacientes foram coletados do banco de dados. Estas biópsias foram classificadas de acordo com a Classificação de Banff. Reação imuno-histoquímica foi empregada para identificar vasos linfáticos, linfócitos T, linfócitos B e macrófagos. Análise histomorfométrica foi empregada para quantificar estes quatros elementos e a fibrose intersticial cortical. RESULTADOS: A presença de vasos linfáticos foi significativamente mais intensa em biópsias com rejeição aguda mediada por linfócitos T e com distúrbios infecciosos (nefropatia do poliomavírus e pielonefrite), quando comparadas à expressão de linfáticos com biópsias sem rejeição e com biópsias com fibrose intersticial e atrofia tubular de etiologia indeterminada. Biópsias com expressão de vasos linfáticos apresentaram escores semiquantitativos da Classificação de Banff mais altos. Os linfócitos B túbulo-intersticiais apresentaram maior concentração em amostra com presença de vasos linfáticos. A linfangiogênese não demonstrou influência sobre desfechos clínicos relevantes, como função renal e sobrevida do enxerto. CONCLUSÃO: O presente estudo associa a linfangiogênese com distúrbios inflamatórios túbulo-intersticiais do enxerto (rejeição aguda mediada por linfócitos T e infecções) e com infiltrado de linfócitos B. No entanto, a expressão de linfáticos não foi associada à influência sobre a função e a sobrevida do enxertoINTRODUCTION: The role of lymphangiogenesis in human kidney allograft is currently unknown. Controversial results have arisen from few publications available. This study intends to evaluate the influence of lymphatics on relevant clinical and pathological aspects of renal transplantation. METHODS: Clinically indicated biopsies from patients who underwent renal transplantation with allografts from deceased donors at the Renal Transplantation Unit of the Clinics Hospital of the University of São Paulo Medical School from January of 2007 to December of 2009 were selected and clinical data of these patients were retrieved from the database. These biopsies were classified according to the Banff Classification. Immunohistochemistry was used to identify lymphatic vessels, T lymphocytes, B lymphocytes, and macrophages. Morphometric analysis was employed to quantify their expression and cortical interstitial fibrosis. RESULTS: Lymphatic vessel formation was significantly higher in biopsies with acute T-cell mediated rejection and infectious disorders (polyomavirus-associated nephropathy and pyelonephritis) compared with no rejection and interstitial fibrosis and tubular atrophy without evidence of any specific etiology. Biopsies with expression of lymphatics presented higher levels of semiquantitative scores of the Banff Classification. B lymphocytes infiltrate was more intense in biopsies with lymphatics compared with those without the vessels. Lymphangiogenesis had no effect on important clinical parameters examined (graft function and graft survival two years post transplant). CONCLUSION: The present results associate lymphangiogenesis with kidney allograft tubulointerstitial inflammation (ATCMR and infectious disorders) and with B lymphocytes infiltrate. However, the presence of lymphatic vessels was not associated with any influence on graft function and survival
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Engstrand, Mats. "Cellular Immune Responses to Allografts and Cytomegalovirus". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3441.
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Vicaretti, Mauro. "Investigation of prosthetic vascular graft infections in an ovine model". Thesis, The University of Sydney, 2001. https://hdl.handle.net/2123/27714.
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This thesis examines the in-vitro and in-vz’vo effect of rifampicin (a known antistaphylococcal
agent) following prosthetic graft impregnation, to prevent and treat
Staphylococcus epidermidis (MRSE) and Staphylococcus aureus (MRSA) prosthetic
vascular graft infections. In addition the effects of rifampicin on intirnal hyperplasia were
analysed.
Using a disc difiusion technique, one square centimetre segments of Gelsofi, Gore-Tex,
Fluoropassiv or Thoratec were impregnated with rifampicin at concentrations of
1.2mg/ml, 10 mg/ml or 30 mg/ml and placed on a bacterial lawn of MRSA or MRSE.
With increasing rifampicin concentration, all grafis displayed increased initial zones of
inhibition and length of time of antibacterial activity. Fluoropassiv and Gelsofi were the
superior grafts at all studied rifampicin concentrations.
Using an established ovine model in which grafis were interposed in the carotid artery of
sheep, it was shown that all grafts studied in-vitro were easily infected with an
overwhelming dose of MRSA or MRSE, and once infected would harbour the infective
micro—organism.
From our preliminary in-vitro and in-vivo results Gelsoft was chosen as the graft of choice
for the subsequent in-vivo (ovine model) experimentation.
Interposition Gelsofi grafts at concentrations of 1.2mg/ml or 10 mg/ml rifampicin was
inoculated with 108 colony forming units (CFU) of MRSE or MRSA and compared to
infected non-impregnated Gelsoft grafts. Grafis were harvested at three weeks.
Our findings showed that rifampicin at both 1.2 mg/ml and 10 mg/ml reduced the
incidence of abscess formation, anastomotic disruption and grafi thrombosis for both
MRSE and MRSA. In addition overall positive cultures were significantly reduced with
increasing rifampicin concentration for MRSE and MRSA infected grafts.
MRSE or MRSA infected Gelsofi grafts were replaced at three weeks with 1.2 mg/ml or
10 mg/ml rifampicin impregnated Gelsofi grafts. The replacement grafts were
subsequently removed following a further three weeks. No significant improvements were
noted for the recorded macroscopic or bacteriological parameters with increasing
rifampicin concentration with the MRSA infected grafts. However, with regards to S.
epidermidis, a concentration of 10 mg/ml effectively reduced the total number of infected
grafts compared to both the control group and the 1.2 mg/ml rifampicin group.
Varying the concentration of rifampicin between nil, 1.2mg/ml and 10 mg/ml had no
significant impact on the formation of intimal hyperplasia or platelet aggregation.
These results demonstrated that 10 mg/ml rifampicin impregnation of Gelsofi grafts is an
effective means of preventing MRSA and MRSE prosthetic graft infection and treating
established MRSE graft infection without contributing to intimal hyperplasia.
14
Pettersson, Nils y Gabriella Johnsson. "Riskfaktorer för postoperativa sårinfektioner efter Coronary Artery Bypass Graft". Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-225259.
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Bakgrund: Postoperativa sårinfektioner [PSI] är en allvarlig komplikation och ett hälsoproblem som orsakar lidande för patienten. Såsom vid alla operativa ingrepp förekommer en risk att få PSI i operationssåret/-såren efter Coronary Artery Bypass Graft [CABG], men det finns redan en rad kända riskfaktorer som ökar risken för PSI. Syfte och metod: Syftet med rapporten var att undersöka om kombinationen av ett antal sedan tidigare kända riskfaktorer ökade risken för PSI efter CABG på ett mellansvenskt sjukhus åren 2009-2012. En retrospektiv journalgranskningsstudie med totalt 228 patienter genomfördes. Resultat: Av 228 undersökta hade totalt 50 patienter rapporterat sårinfektion och 73 patienter hade ≥ 3 riskfaktorer. Bland de som hade ≥ 3 riskfaktorer rapporterade 32,9% PSI och bland de som hade < 3 riskfaktorer rapporterade 16,8% PSI. Risken att få PSI efter CABG-kirurgi är nästan dubbelt så stor (RR=1,960) hos patienter med ≥ 3 riskfaktorer jämfört med patienter med < 3 riskfaktorer (X2=7,516 df=1 p=0,006). Slutsats: Det finns en signifikant högre risk för PSI efter CABG vid förekomst av tre eller fler än tre patientrelaterade riskfaktorer jämfört med färre än tre riskfaktorer. Fler, större studier av detta slag efterfrågas då denna rapport kan ge en fingervisning om hur situationen föreligger på ett mellansvenskt sjukhus.Objective: Postoperative surgery site infections [SSI] is not only a severe complication but a health problem which often cause suffering and prolonged hospitalization among afflicted patients. As with all surgical procedures, a coronary artery bypass graft [CABG] always implicates a risk for SSI and a number of risk factors have to be taken into account when dealing with it. The objective of this report is to investigate if a combination of several patient-related risk factors implicates greater risk of getting SSI after CABG. Method: A quantitative retrospective journal review of 228 patients who completed a CABG between 2009-2012 was performed on a university hospital in central Sweden. Result: Among 228 patients a total of 50 reported SSI and 73 patients had ≥ 3 patient-related risk factors. Among those who had ≥ 3 risk factors 32.9% reported SSI and among those who had < 3 risk factors 16.8% reported SSI. The risk of getting SSI after CABG is almost twice as high (RR = 1.960) in patients with ≥ 3 risk factors compared to patients with < 3 risk factors (X2 = 7.516 df = 1 p = 0.006). Conclusion: There is a significantly higher risk of getting SSI after CABG in the presence of three or more than three patient-related risk factors, compared with fewer than three risk factors. More, larger studies of this kind are in demand since this report provides an indication of how the situation may prevail on a central Swedish university hospital.
15
Yao, Felix Caspar. "Investigation on the risk of viral infection in musculoskeletal grafts". University of Western Australia. School of Surgery, 2010. http://theses.library.uwa.edu.au/adt-WU2010.0068.
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[Truncated abstract] Around 50,000 hip and knee replacements are performed every year in Australia and this number has been increasing by around 13% annually since 1998 (Transplantation Society 2006). The incidence and number of revision surgery has increased by a similar proportion. Autogenous bone or allograft is still the gold standard grafting material and is currently used in a variety of reconstructive surgical procedures. The use of any allograft material carries with it the risk of transfer of disease from donor to recipient. These tissues can transmit the same viral and bacterial infections as blood, and the products of a single donation may be transplanted to several recipients. In contrast to blood, musculoskeletal tissues may come from surgical and cadaveric donation. Overall, the prevention of infection relies on the maintenance of rigid protocols for procurement, donor and allograft testing, secondary sterilisation, and the adherence to internal safety standards within the tissue banks. This thesis aims to determine the risk of viral infection among musculoskeletal tissue donors in Australia. We retrieved and analysed data retrospectively from three large tissue banks in Australia (Perth, Queensland, Victoria). This includes 12,415 musculoskeletal tissue donors, 10,937 of which are surgical donors and 1,478 of which are deceased donors, for the period of 1993 -2004. This data was analysed to determine the prevalence and incidence of viral infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) in musculoskeletal allografts. The results indicate that the risk of viral infection from musculoskeletal tissue transplantation in Australia is low. ... The results indicate that the overall prevalence of screened transfusion-transmitted viral infections did not vary significantly for musculoskeletal donors over the study period, despite falling in the general population and first-time blood donors. In tissue donors, HIV incidence significantly decreased over time, and HBV decreased significantly during 1999-2001; however, there was an apparent increase in the estimated incidence of HCV in 2002-2004 compared with earlier years. Furthermore the residual risk estimate of HIV in the period 2002-2004 has declined 5-fold compared to estimates in the period 1993-1995. This is perhaps due to greater awareness of high risk behaviours among donors, improvement in donor recruitment and an overall decrease in infection levels in the general population. Musculoskeletal tissue is second only to blood as the most frequent transplanted human tissue. Viral infection is a potential complication of tissue transplantation. In this thesis the rates of HIV, HBV, HCV and HTV infection in musculoskeletal donors in Australia were identified and then compared with results in published data from Canada, Scotland and the United States. The study also compared that result with first-time blood donors because they have satisfied similar donor selection criteria (Galea et al. 2006). The results indicate that prevalence and incidence estimates for viral infection in Australian tissue donors are higher than those in blood donors. This was also reported in studies from other countries. Accordingly, it is crucial that viral prevalence and incidence be monitored to evaluate the safety of tissue supply and to improve donor selection processes.
16
Fradet, Guy. "Factors in the prophylaxis of infection of prosthetic vascular grafts". Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=65444.
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Scroggins, Sabrina Marie. "Generation and characteriztion of regulatory dendritic cells for the amelioration of acute graft versus host disease". Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/2011.
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Despite Human Leukocyte Antigen (HLA) matching and use of immunosuppressive drugs, graft-versus-host disease (GVHD) following hematopoietic stem cell transplant (HSCT) is prevalent and often fatal. Additionally, older HSCT recipients experience increased morbidity and mortality. Prophylactic treatment with age-matched syngeneic (recipient strain-derived) cultured regulatory DC (DCreg) has been shown to decrease GVHD-associated mortality in young bone marrow transplanted (BMT) mice. The purpose of this study was to investigate: 1) the potential to generate DCreg from older mice and their subsequent ability to ameliorate GVHD in older BMT mice, 2) the mechanism(s) by which DCreg mitigate GVHD in vivo, 3) the ability of DCreg-treated BMT mice to respond to infectious pathogens, and 4) whether DCreg can be generated under clinically relevant conditions from healthy donor and HSCT recipient PBMCs.
To evaluate the efficacy of DCreg treatment in older mice, complete MHC-mismatched BMT mice were treated with DCreg (hereafter referred to as DCreg-treated BMT mice). Although DCreg treatment ameliorated GVHD in older BMT mice, these mice had increased morbidity and decreased survival compared to their young counterparts.
Following transfer into BMT mice, older DCreg failed to increase inhibitory molecule (PD-L1 and PIR B) expression while significantly upregulating co-stimulatory molecule (CD40 and CD80) expression, conversely young DCreg upregulated inhibitory molecules as well as co-stimulatory molecules. These phenotypic differences between young and older DCreg in vivo provide a potential mechanism for modestly increased morbidity and mortality in older DCreg-treated BMT mice relative to their young counterparts. Indeed, BMT mice treated with DCreg deficient in PD-L1 or PIR B had significantly reduced overall survival, thus both molecules are required for optimal GVHD mitigation.
A murine H1N1 influenza (IAV) infection model was used to assess the donor immune system's capacity to respond to relevant antigens other than those responsible for GVHD. Surprisingly, sub-lethally IAV-infected DCreg-treated BMT mice began to die after d. +21 and all were deceased by d. +25. Virus-specific CD8+ T cell and antibody (Ab) responses were undetectable following primary infection. Interestingly, following a prime-boost infection strategy, DCreg-treated BMT mice survived lethal IAV challenge with no signs of morbidity and had demonstrable IAV-specific Ab and CD8+ T cell responses. Thus a prime-boost IAV infection strategy establishes a protective immune response in the DCreg-treated BMT mice and underscores the potential role vaccination may play in establishing immune competence in DCreg-treated BMT mice.
We investigated whether human DCreg can be generated under clinically relevant conditions: 1) following peripheral blood mononuclear cell (PBMC) cryopreservation, 2) in bovine serum-free media, and 3) from older individuals and HSCT recipients. DCreg were generated from healthy donor and HSCT patient PBMCs isolated from young (old) and older (> 50 years old) individuals by culturing cells in X-vivo serum-free.
Human DCreg generated from both young and older healthy donor PBMCs had comparable numbers, surface molecule phenotype, cytokine production, and able to induce Treg. Cryopreserved and fresh PBMCs generated DCreg with similar phenotypes and cytokine production. DCreg generated from HSCT recipients maintained low co-stimulatory molecule and high inhibitory molecule expression as well as immunosuppressive cytokine production. These studies confirm DCreg can be generated under clinically relevant conditions.
18
Wu, Wong David Jasen Y. "Application of Affinity Polymer Coating to ePTFE Arteriovenous Grafts to Improve both Passive and Active Infection Prevention for Hemodialysis". Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1554998833025791.
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Heinrichs, Jessica Lauren. "Antigen Specific Induced T Regulatory Cellular Therapy for Graft-Versus-Host Disease Following Allogeneic Bone Marrow Transplantation". Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6093.
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Allogeneic hematopoietic stem cell transplantation (allo-HCT) has been a successful cellular therapy for patients suffering from hematological malignancies for many decades; however, the beneficial effects of graft-versus-leukemia (GVL) are classically offset by graft-versus-host disease (GVHD). GVHD occurs when major and/or minor human leukocyte antigen (HLA) mismatches between donor and recipient cause rapid expansion and activation of donor effector T cells (Teffs) resulting in end organ damage to the recipient’s epithelial tissues. Given the lymphoproliferative nature of this disease, the standard treatment option is broad immunosuppression, which can result in primary disease relapse, steroid refractory GVHD, and/or opportunistic infection. A more targeted therapy that can selectively suppress GVH responses with maintained GVL responses would achieve the optimal goal of allo-HCT. Regulatory T cells (Tregs) both natural (nTregs) or induced (iTregs) could be potential cellular therapies for the treatment of GVHD, given their innate suppressive function. Initial clinical trials using nTregs have yielded positive results; however, nTreg cellular therapy has been cumbersome due to the necessity for large scale ex vivo expansion given their low yield within an apheresis product and non-specific suppression. Conversely, iTregs can be generated from naïve T cells thus decreasing ex vivo culture times and can be educated with specific antigen thus providing targeted suppression, but a consensus on their efficacy for GVHD therapy has not been reached. Therefore, we investigated the efficacy of antigen specific iTreg therapy for the prevention of GVHD while maintaining GVL responses.
In Chapter 2, we evaluated the effectiveness of monoclonal HY-specific iTregs in GVHD attenuation. We chose HY as a target antigen because it is a naturally processed, ubiquitously expressed minor mismatch antigen carried by only male donors/recipients cited to increase GVHD prevalence when donor and recipient are sex-mismatched. Utilizing HY-transgenic mice in which all T cells recognize HY antigen exclusively, we generated HY specific iTregs which effectively attenuating GVHD in male, but not female recipients in three murine bone marrow transplantation (BMT) models (major mismatch, parent to F1, and miHAg mismatch). We found HY specific iTregs lost stability in female recipients but remained stable and suppressive in male recipients suggesting expression of HY antigen was required for their suppressive function and stability. GVL responses were not compromised with the addition of HY specific iTregs in recipient mice using a pre-established tumor model. Thus, HY-specific iTregs can be generated and suppress GVHD in an antigen-dependent manner while sparing the GVL effect.
In Chapter 3, we extend our findings in Chapter 2, which provided proof of principle that antigen specific iTregs effectively control GVHD; however, this therapy has a limited translational potential. Therefore, we generated alloreactive CD4 and CD8 iTregs and evaluated GVHD attenuation and GVL preservation in either full or haplo-MHC mismatched BMT models. We found alloreactive CD4 iTregs significantly suppress lethal GVHD, but completely abrogated the GVL effect against aggressive tumors. Conversely, alloreactive CD8 iTregs moderately attenuated GVHD and possessed direct cytotoxicity against tumor cells. Therefore, to rescue the impaired GVL effect mediated by CD4 iTregs, we established a combinational therapy with CD8 iTregs. Indeed we found combination CD4 and CD8 iTreg therapy significantly suppressed GVHD while sparing GVL responses compared to either CD4 or CD8 singular therapy. Mechanistically, this was achieved by potent suppression of both CD4 and CD8 Teffs coupled with preserved cytolytic molecule expression by both CD8 iTregs and Teffs.
Taken together, we propose antigen specific iTreg therapy can effectively attenuate GVHD while preserving GVL responses. We further uncovered unique characteristics of CD4 and CD8 iTregs that can be exploited to achieve the optimal cellular therapy following allo-HCT.
20
Fu, Jianing. "Targeting T-bet for Prevention of Graft-Versus-Host Disease and Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation". Scholar Commons, 2015. http://scholarcommons.usf.edu/etd/5828.
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapeutic option for many malignant diseases. However, the efficacy of allo-HSCT is limited by the occurrence of destructive graft-versus-host disease (GVHD). Since allogeneic T cells are the driving force in the development of GVHD, their activation, proliferation, and differentiation are key factors to understanding GVHD pathogenesis. On the other hand, antigen-presenting cells (APCs) are essential for allogeneic T-cell priming and the development of GVHD. The T-box transcription factor T-bet is a master regulator for IFN-γ production and Th1 differentiation. T-bet also regulates the functions of APCs including dendritic cells (DCs) and B cells. Therefore, we investigated the role of T-bet in T cell responses, as well as on APC functions, in acute GVHD (aGVHD) using murine models of allogenic bone marrow transplantation (allo-BMT).
In Chapter 2, we evaluated the roles of T-bet and IFN-γ in T-cell responses. T-bet-/- T cells induced significantly less GVHD compared with either wild-type (WT) or IFN-γ-/- counterparts in CD4-driven major histocompatibility complex (MHC)- or minor histocompatibility antigen (miHA)-mismatched models. We defined several T-bet-dependent but IFN-γ-independent molecules that may account for this distinct outcome. Further study indicates that T-bet also controls the optimal activity of Th17 cells to induce GVHD. Moreover, the compromised graft-versus-leukemia (GVL) effect of T-bet-/- T cells could be essentially reversed by IL-17 neutralization. Thus, targeting T-bet or regulating its downstream effectors independent of IFN-γ may be a promising strategy to control GVHD in the clinic.
In Chapter 3, we evaluated the role of T-bet on APCs and found that T-bet-/- recipients developed much milder GVHD than their WT counterparts in MHC-mismatched or CD4-depedent miHA-mismatched models. As the functional readout of APCs, allogeneic donor T cells, particular CD4 subpopulation, significantly reduced IFN-γ production, proliferation and migration, and caused less damage in liver and gut in T-bet-/- recipients. We further observed that T-bet on recipient hematopoietic APCs, particular DCs, was primarily responsible for donor T-cell response and pathogenicity in GVHD. In fact, Trail/DR5 interaction served as a major signaling pathway responsible for donor T-cell apoptosis and impaired GVHD development in T-bet-/- recipients. Furthermore, T-bet expression on the host is largely dispensable for the GVL effect.
Taken together, we propose that T-bet is a potential therapeutic target for the control of GVHD through regulating T cells as well as APCs. We believe further exploration and understanding of the immunobiology of T-bet in controlling the activities of T cells and APCs in GVHD will expand therapeutic options for the continuing success of allo-HSCT.
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Pidala, Joseph. "Achievement of Transplantation Tolerance: Novel Approaches and Mechanistic Insights". Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5104.
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Current immune suppressive strategies fail to induce donor-recipient immune tolerance after allogeneic hematopoietic cell transplantation. Accordingly, patients suffer morbidity and mortality from graft vs. host disease (GVHD) and prolonged immune suppressive therapy. Biologic insight into transplantation tolerance is needed, and translation of such insight to novel clinical strategies may improve clinical outcomes. We report original investigation at seminal phases of this process including initial prophylactic immune suppression, onset of acute graft vs. host disease, and ultimate immune suppression discontinuation: In a controlled randomized clinical trial, we demonstrate that sirolimus-based immune suppression reduces risk for acute GVHD, ameliorates the severity of subsequent chronic GVHD, and supports reconstitution of functional regulatory T cells. Study of tissue-infiltrating CD4+ T cell subsets in acute GVHD target organs supports a pathogenic role for Th17 cells. Finally, we demonstrate that peripheral blood transcriptional biomarkers provide mechanistic insight into human transplantation tolerance. These data signal progress, and suggest rational translational efforts to achieve transplantation tolerance.
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Larsson, Kajsa. "Cytomegalovirus after allogeneic haematopoietic stem cell transplantation : complications in the era of CMV-specific antiviral treatment /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-735-5/.
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Graf, Stefanie Verfasser], Ulrike [Akademischer Betreuer] [Protzer-Knolle y Iris [Akademischer Betreuer] Antes. "Role of the immunosuppressive environment during the course of a hepatitis B virus infection / Stefanie Graf. Gutachter: Ulrike Protzer ; Iris Antes. Betreuer: Ulrike Protzer". München : Universitätsbibliothek der TU München, 2015. http://d-nb.info/107635968X/34.
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Forman, Daron. "Viral Abrogation of Stem Cell Transplantation Tolerance Causes Graft Rejection and Host Death by Different Mechanisms: A Dissertation". eScholarship@UMMS, 2002. https://escholarship.umassmed.edu/gsbs_diss/72.
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Tolerance-based stem cell transplantation using sub-lethal conditioning is being considered for the treatment of human disease, but safety and efficacy remain to be established. In order to study these two issues, we first established that mouse bone marrow recipients treated with sub-lethal irradiation plus transient blockade of the CD40-CD154 costimulatory pathway develop permanent hematopoietic chimerism across allogeneic barriers. Our conditioning regimen of 6 Gy irradiation, a short course of anti-CD154 mAb and 25 million fully allogeneic BALB/c bone marrow cells consistently produced long-term, stable, and multilineage chimerism in C57BL/6 recipients. Furthermore, chimeric mice displayed donor-specific transplantation tolerance, as BALB/c skin allografts were permanently accepted while third-party CBA/JCr skin allografts were promptly rejected. We next determined both the safety and efficacy of this protocol by infecting chimeric mice with lymphocytic choriomeningitis virus (LCMV) either at the time of transplantation or at several time points afterwards. Infection with LCMV at the time of transplantation prevented engraftment of allogeneic, but not syngeneic, bone marrow in similarly treated mice. Surprisingly, infected allograft recipients also failed to clear the virus and died. Post-mortem study revealed hypoplastic bone marrow and spleens. Hypoplasia and death in these mice required the combination of 6 Gy irradiation, LCMV infection on the day of transplantation, and an allogeneic bone marrow transplant but did not require the presence of anti-CDl54 mAb. Allochimeric mice infected with LCMV 15 days after transplantation were able to survive and maintain their bone marrow graft, indicating that the deleterious effects of LCMV infection on host and graft survival are confined to a narrow window of time during the tolerization and transplantation process. The final section of this thesis studied the mechanisms of graft rejection and death in sublethally irradiated recipients of allogeneic bone marrow and infection with LCMV at the time of bone marrow transplantation. Infection of interferon-α/β receptor knockout mice at the time of transplantation prevented the engraftment of allogeneic bone marrow, but the mice survived. Therefore, IFN-αβ is involved in the development of marrow hypoplasia and death, whereas a second mechanism is involved in blocking the development of chimerism in these mice. Through the use of depleting mAb's and knockout mice we demonstrate that three types of recipients survived and became chimeric after being given sublethal irradiation, anti-CD154 mAb, an allogeneic bone marrow transplant and a day 0 LCMV infection: mice depleted of CD8+ T cells, CD8 knockout mice, and TCR-αβ knockout mice. Our data indicate that the mediator of bone marrow allograft destruction in LCMV-infected mice treated with costimulatory blockade is a radioresistant CD8+ NK1.1- TCRαβ+ T cell. We conclude that a non-cytopathic viral infection at the time of transplantation can prevent engraftment of allogeneic bone marrow and result in the death of sub-lethally irradiated mice treated with costimulation blockade. The abrogation of allogeneic bone marrow engraftment is mediated by a population of CD8+ NK1.1- TCRαβ+ T cells and the mediator of hypoplasia and death is viral induction of IFN-αβ.
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Silva, Daniela Terezinha Richter da. "Avaliação dos níveis séricos e de ingestão de micronutrientes em pacientes submetidos ao transplante de células tronco hematopoiéticas". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/139799.
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Introdução: O transplante de células tronco hematopoiéticas é reconhecidamente uma opção terapêutica para doenças neoplásicas hematológicas, tumores sólidos, deficiências imunológicas e doenças metabólicas. É um procedimento associado a uma alta freqüência de complicações agudas e crônicas, causadas pela toxicidade do regime de condicionamento, dentre elas a mucosite, Doença do Enxerto versus Hospedeiro - DECH e infecções. Essas complicações podem causar grandes mudanças na composição corporal através de mudanças no metabolismo, piorando o estado nutricional. Um adequado consumo de alguns micronutrientes como zinco, vitamina D e ferro, tem sido investigado como forma de evitar ou minimizar essas complicações. Objetivo: Avaliar em pacientes submetidos a transplante de células tronco hematopoiéticas os níveis séricos de zinco, vitamina D e ferritina e o seu impacto nos desfechos do TCTH alogênico e os níveis de ingestão de zinco, vitamina D e ferro. Métodos: Foram avaliadas as dosagens séricas de zinco, vitamina D e ferritina, e os níveis de ingestão de zinco, vitamina D e ferro, os tipos de condicionamento, o grau de DECH e mucosite, a presença de infecções e o estado nutricional. Resultado: Foram incluídos na análise 32 pacientes. Não foi encontrado associação significativa entre a deficiência sérica de Zinco e mucosite e os níveis elevados de ferritina sérica com a ocorrência de infecções. Deficiência sérica de vitamina D aos 45 dias pós transplante foi associado com o desenvolvimento de DECH. Conclusão: Os nossos resultados reforçam a importância dos pacientes manterem os níveis adequados de micronutrientes e reforçam o papel da vitamina D na prevenção de DECH durante o TCTH.Introduction: The transplantation of hematopoietic stem cells is recognized as a treatment option for hematological neoplastic diseases, solid tumors, immune deficiencies and metabolic diseases. It is a procedure associated with a high frequency of acute and chronic complications caused by the toxicity of the conditioning regimen, among them mucositis, Graft-versus-Host Disease - GVHD and infections. These complications can cause major changes in body composition through changes in metabolism, worsening the nutritional status. An adequate intake of some micronutrients such as zinc, vitamin D and iron, has been investigated as a way to avoid or minimize these complications. Objective: To evaluate in patients undergoing hematopoietic stem cell transplantation serum levels of zinc, vitamin D and ferritin and its impact on the outcomes of allogeneic HSCT and zinc intake levels of vitamin D and iron. Method: The following aspects were evaluated: serum levels of zinc, vitamin D and ferritin, and zinc intake levels of vitamin D and iron, the conditioning types, the degree of GVHD and mucositis, the presence of infections, the nutritional status. Result: The analysis included 32 patients. No significant association has been found between zinc serum deficiency and mucositis and elevated levels of serum ferritin with the occurrence of infections. The serum deficiency of vitamin D at 45 days post-transplantation has been associated with the development of GVHD. Conclusion: Our results reinforce that it is important for the patients to maintain adequate levels of micronutrients and reinforce the role of vitamin D in the prevention of GVHD during the HSCT. Keywords: hematopoietic stem cell transplantation, GVHD, mucositis, infections, Vitamin D, ferritin, zinc, nutritional status.
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Semple, Kenrick. "Generation and Application of Antigen-Specific Induced Regulatory T cells in Allogeneic Bone Marrow Transplantation". Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3340.
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CD28 co-stimulation is required for the generation of naturally occurring regulatory T cells (nTregs) in the thymus through Lck-signaling. However, high level of CD28 suppresses the generation of induced Tregs (iTregs) from naïve CD4 T cells, although underlying mechanism(s) has not been defined. Here we investigated the role of CD28-mediated signaling pathways in the suppression of Treg generation. We used a series of transgenic (Tg) mice on CD28-deficient background that bears WT CD28 or mutated CD28 in its cytosolic tail incapable of binding to Lck, PI3K or Itk. Regardless of exogenous IL-2, strong CD28 costimulation suppressed iTreg generation through Lck signaling. Using a GVHD model to test the role of CD28-mediated iTreg suppression in T cell pathogenicity in vivo, we found that CD28-Lck T cells induced significantly less GVHD than T cells from CD28-WT mice. Furthermore, we found that the recipients of T cells from CD28-Lck mice generated significantly more iTregs than those with T cells from CD28-WT, which contribute to reduced graft-versus-host disease (GVHD) development in recipients of CD28-Lck T cells. These results indicate that CD28 costimulation can negatively regulate Treg generation and may provide an avenue for control of T-cell immunity or tolerance by regulating Tregs using the CD28 signal as a target. We went a step forward and investigated the therapeutic potential of antigen-specific iTregs in the prevention of GVHD. Donor hematopoietic stem cells and mature T cells are transplanted into a lymphopenic host to potentially cure many cancers and hematopoietic diseases like leukemia in bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HCT), but the frequent development of GVHD is the main drawback of this treatment. nTregs suppress the development of GVHD and may spare graft-versus-tumor effect. However, nTregs are a minor (~5%) subpopulation of CD4 helper T cells in healthy individuals, and using in vitro expanded nTregs is a common strategy to test their therapeutic potential in BMT. The concern of in vitro expanded nTregs may include their stability of Foxp3 (master regulatory gene for the development and function of regulatory T cell) expression and suppressive function, survival in vivo, and the non-selective suppression of the pre-activated nTregs. Antigen-specific activation of the regulatory T cells is important for optimal function. In this study, we used an alternative strategy to generate antigen-specific, iTregs and assessed their suppressive potential by comparing their effectiveness in preventing GVHD with polyclonal iTregs. We found that antigen-specific iTregs prevented GVHD lethality in recipients that expressed the target antigen, but were not protective of recipients who did not express the target antigen. Furthermore, antigen-specific iTregs were significantly more efficient than those polyclonal Tregs in the prevention of GVHD. These results reveal the therapeutic potential of antigen-specific iTregs to prevent GVHD efficiently and selectively, and provide the rationale to use antigen-specific iTregs in clinical HCT.
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García, Cadenas Irene. "Complicaciones del trasplante alogénico de progenitores hematopoyéticos: enfermedad de injerto contra el receptor y predisposición a infecciones. estrategias de mejora". Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/405324.
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El trasplante alogénico de progenitores hematopoyéticos (alo-TPH) representa la única estrategia curativa para un grupo no desdeñable de enfermedades hematológicas previamente letales. Sus resultados, mejoran de forma progresiva con el paso de los años, sin embargo, la mortalidad relacionada con el trasplante (MRT) oscila entre el 15 y el 50% en función de las características del paciente y el tipo de trasplante.
La presente tesis doctoral ahonda en las dos principales causas de MRT, la enfermedad injerto contra el receptor aguda (EICRa) y las infecciones oportunistas, que condicionan gran parte de la morbi-mortalidad asociada al procedimiento y se encuentran íntimamente relacionadas. En este trabajo se identifican, en primer lugar, aspectos que suponen un problema habitual en la práctica clínica diaria que limitan la mejora de los resultados globales del procedimiento y se proponen, a continuación, estrategias prácticas para contrarrestar estas dificultades.
En relación a la EICR, los ámbitos en que se centra el interés son, en primer lugar, el impacto de un manejo adecuado de la profilaxis farmacológica en la aparición de EICR aguda con la importancia de evitar niveles infraterapéuticos de Ciclosporina A en sangre las primeras semanas post-trasplante para mejorar los resultados a largo plazo y posteriormente, una vez identificada dicha complicación, y especialmente en el caso de refractariedad a esteroides, un segundo trabajo remarca la importancia del apropiado diseño y el seguimiento prolongado de los pacientes a la hora de evaluar la eficacia de las distintas estrategias de rescate.
En el ámbito de las infecciones oportunistas, se muestran datos epidemiológicos sobre la incidencia, momento de aparición, patógenos responsables e impacto de las infecciones en la morbi-mortalidad en el ámbito de la EICR refractaria, un escenario de conocido alto riesgo en el que hasta la fecha, no se habían descrito datos que permitan optimizar las estrategias de profilaxis y tratamiento anticipado aplicadas en otros escenarios.
Cada uno de los trabajos incluidos en esta Tesis Doctoral aporta información detallada y original sobre aspectos concretos de las complicaciones post-TPH y su conjunción permite una visión global de la situación actual y las posibles estrategias de mejora que supera, sin duda, la suma de las partes.Allogeneic stem cell transplantation (allo-SCT) is the only curative therapy for many patients with hematologic malignancies. However, this treatment is limited by a high morbidity and mortality that ranges from 15% to 50% depending on patient and transplant characteristics. This doctoral thesis focuses on the two main causes of transplant related mortality (TRM), acute Graft-Versus-Host-Disease (aGVHD) and opportunistic infections, which are closely associated and cause significant morbidity and mortality in the early post-trasplant period. Firstly, this work identifies several issues that remain common obstacles in allo-SCT daily clinical practice. Secondly, evidence-based interventions are proposed to overcome these difficulties. In terms of GVHD, the interest areas are, firstly, the impact of an adequate pharmacological prophylaxis on the occurrence of acute GVHD, especially the importance of avoiding infraterapeutic levels of Ciclosporin A in the blood the first four weeks after SCT to improve long-term outcomes and secondly, once this complication has been developed, and especially in the case of steroid refractoriness, a second report stresses the importance of the appropriate design and long term follow-up of affected patients to evaluate the effectiveness of the different salvage strategies. In the field of opportunistic infections, epidemiological data on the incidence, time of onset, responsible pathogens and impact of infections on morbidity and mortality in patients with refractory acute GVHD (a well known high risk scenario in which data are lacking) are shown. This information seems helpful to optimize monitoring, prophylactic and pre-emptive strategies that have been implemented in other high-risk groups. All manuscripts included in this doctoral thesis provide detailed and original information on specific aspects of post-SCT complications and their conjunction allow a final view of the current situation and possible strategies for improvement of NRM in the SCT field that undoubtedly exceed the sum of the parts.
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Castelli, Jussara Bianchi. "Diagnóstico de vírus por microscopia eletrônica em urina de pacientes com hematúrias/cistite hemorrágica após transplante de medula óssea: associação com aspectos clínicos". Universidade de São Paulo, 2000. http://www.teses.usp.br/teses/disponiveis/5/5144/tde-14072014-114006/.
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Pacientes submetidos ao transplante de medula óssea, apresentando hematúria/cistite hemorrágica, tiveram amostras de urina analisadas pela microscopia eletrônica. Esta foi a técnica escolhida de pesquisa viral pela sua confiabilidade. Noventa em 402 pacientes submetidos ao transplante de medula óssea neste serviço apresentaram hematúria/cistite hemorrágica (incidência de 22%). O estudo por microscopia eletrônica foi realizado em 72 destes pacientes com hematúria/cistite hemorrágica (grupo de estudo), identificando 55,6% (40/72) de positividade viral. Foram também estudadas amostras de urina de 12 pacientes submetidos ao transplante de medula óssea sem hematúria/cistite hemorrágica (grupo controle); houve associação significante entre a presença de vírus e hematúria/cistite hemorrágica (p<0,01 - Teste exato de Fisher). No grupo com hematúria/cistite hemorrágica, 65% (26/40) dos vírus detectados pertenciam à família Poliomaviridae, 30% (12/40) à Adenoviridae, e 5% (2/40) foram positivos para ambas as famílias. Houve associação entre a positividade para vírus e a presença da doença enxerto-contra-hospedeiro (p=0,05-x2) e o de início tardio (>dia+21) da H/CH (P=0,04-x2), bem como entre a doença enxerto-contra-hospedeiro e a severidade da H/CH (p=0,04-x2). O presente estudo mostra que a microscopia eletrônica é uma ferramenta útil para detecção de vírus na urina de pacientes submetidos ao transplante de medula óssea apresentando hematúria/cistite hemorrágica e que o vírus provavelmente tem um papel no desenvolvimento do sangramento urinário, o qual é agravado pelo doença enxerto-contra-hospedeiro. A microscopia eletrônica deveria ser realizada rotineiramente para guiar as outras técnicas de detecção viral, como a imunocitoquímica e biologia molecular.Patients submitted to bone marrow transplantation presenting hematuria/hemorrhagic cystitis had the urine analyzed by electron microscopy. It was the elected technique for viral search because its reliability. Ninety from 402 patients submitted to bone marrow transplantation at this service showed hematuria/hemorrhagic cystitis (incidence of 22%). Electron microscopy study was performed in 72 of these patients with hematuria/hemorrhagic cystitis (study group), identifying 55.5% (40/72) of viral positivity. It was also study the urine of 12 patients submitted to bone marrow transplantation without hematuria/hemorrhagic cystitis (control group); there was a significant association between the presence of virus and hematuria/hemorrhagic cystitis (p<0.01). In the hematuria/hemorrhagic cystitis group, 65% (26/40) of the virus belonged to Poliomaviridae family, 30% (12/40) to Adenoviridae, and 5% (2/40) to both families. There was association between the status of graft-versus-host disease and positivity for virus (p=0.05), as well as between graft-versus-host disease and the severity of hematuria/hemorrhagic cystitis (p=0.04). The present study shows that electron microscopy is a useful tool for detection of virus in urine of patients submitted to bone marrow transplantation presenting hematuria/hemorrhagic cystitis and that the virus probably play a role in the development of the urinary bleeding, which is aggravated by graft-versus-host disease. Electron microscopy should be performed routinely to guide the other techniques for viral detection, like immunocitochemistry and molecular biology.
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Seung, Edward. "CD40-CD154 Blockade Facilitates Induction of Allogeneic Hematopoietic Chimerism and Transplantation Tolerance: A Dissertation". eScholarship@UMMS, 2003. https://escholarship.umassmed.edu/gsbs_diss/103.
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Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Establishment of hematopoietic chimerism created by stem cell transplantation has been shown to prevent and cure a number of autoimmune diseases and induce the most robust and long-lasting form of transplantation tolerance known. However, the realization of the vast clinical potential of hematopoietic chimerism for induction of transplantation tolerance has been impeded by the toxicity of the host conditioning regimen and the development of graft-versus-host disease (GVHD). This thesis describes the development of stem cell transplantation protocols that 1) reduce the host conditioning regimen; and 2) abrogate the development of GVHD. When applied to the treatment of autoimmune diabetic NOD mice, a model of type 1 diabetes, stem cell transplantation was able to 3) prevent autoimmune recurrence; and 4) permit curative pancreatic islet transplantation.
I first describe a tolerance-based stem cell transplantation protocol that combines sub-lethal irradiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With this protocol, I established hematopoietic chimerism in BALB/c mice transplanted with fully allogeneic C57BL/6 bone marrow. All chimeric mice treated with anti-CD154 antibody remained free of graft vs.host disease (GVHD) and accepted donor-origin but not third party skin allografts. It was similarly possible to create allogeneic hematopoietic chimerism in NOD/Lt mice with spontaneous autoimmune diabetes. Pancreatic islet allografts transplanted into chimeric NOD/Lt mice were resistant not only to allorejection but also to recurrence of autoimmunity. I conclude that it is possible to establish robust allogeneic hematopoietic chimerism in sub-lethally irradiated mice without subsequent GVHD by blocking the CD40-CD154 costimulatory pathway using as few as two injections of anti-CD154 antibody. I also conclude that chimerism created in this way generates donor-specific allograft tolerance and reverses the predisposition to recurrent autoimmune diabetes in NOD/Lt mice, enabling them to accept curative islet allografts.
In order to further reduce the impediments associated with the implementation of allogeneic hematopoietic chimerism as a therapeutic modality, I adapted a costimulation blockade-based protocol developed for solid organ transplantation for use in stem cell transplantation. The protocol combines a donor-specific transfusion (DST) with anti-CD154 antibody to induce peripheral transplantation tolerance. When applied to stem cell transplantation, administration of DST, anti-CD154 antibody, and allogeneic bone marrow led to hematopoietic chimerism and central tolerance with no myeloablation (i.e. no radiation) and no GVHD in 3 different strains of mice. The development of donor-specific tolerance in this system was shown to involve deletion of both peripheral host alloreactive CD8+ T cells and nascent intrathymic alloreactive CD8+ T cells. In the absence of large numbers of host alloreactive CD8+ T cells, the cell transfusion that precedes transplantation need not be of donor-origin, suggesting that both allo-specific and non-allo-specific mechanisms regulate engraftment. Agents that interfere with peripheral transplantation tolerance partially impair establishment of chimerism. I conclude that robust allogeneic hematopoietic chimerism and central tolerance can be established in the absence of host myeloablative conditioning using a peripheral transplantation tolerance protocol.
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Schlund, Matthias. "Sinus graft infection management: systematic review". Master's thesis, 2021. http://hdl.handle.net/10284/10729.
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The aim of this study was to systematically review sinus graft infection management in order to define which protocols should be implemented.
The terms searched in each database were “sinus graft infection management”, “maxillary sinus lift infection”, “maxillary sinus graft infection”, “maxillary sinus elevation infection”, “maxillary sinus augmentation infection”. The outcome evaluated both maxillary sinus health and implantological result.
The initial search yielded 1190 results. 18 articles were included counting 3319 patients and 217 sinus graft infections. In every study, all patients obtained finally a disease-free sinus but the outcome regarding the graft and the dental implant was more varied.
It is not possible to define the best treatment protocol for sinus graft infections based on the published data since the level of evidence is poor. Management is very heterogeneous. This review highlighted the necessity of surgical treatment associated with antibiotic therapy.O objetivo deste estudo foi revisar sistematicamente o manejo da infecção do enxerto sinusal, a fim de definir quais protocolos deveriam ser implementados. Os termos pesquisados em cada banco de dados foram “gerenciamento de infecção de enxerto de seio maxilar”, “infecção de elevação do seio maxilar”, “infecção de enxerto de seio maxilar”, “infecção de elevação do seio maxilar”, “infecção de aumento do seio maxilar”. O resultado avaliou a saúde do seio maxilar e o resultado implantológico. A pesquisa inicial gerou 1190 resultados. 18 artigos foram incluídos contando 3319 pacientes e 217 infecções de enxerto de seio. Em todos os estudos, todos os pacientes obtiveram finalmente um seio nasal livre de doença, mas o resultado em relação ao enxerto e ao implante dentário foi mais variado. Não é possível definir o melhor protocolo de tratamento para infecções de enxerto sinusal com base nos dados publicados, uma vez que o nível de evidência é baixo. A gestão é muito heterogênea. Esta revisão destacou a necessidade de tratamento cirúrgico associado à antibioticoterapia.
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Zogala, David. "Přínos FDG PET/CT v diagnostice kardiovaskulárních zánětů". Doctoral thesis, 2020. http://www.nusl.cz/ntk/nusl-411898.
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1 Abstract Aim: To evaluate the diagnostic performance of FDG PET/CT in the detection of stent graft infection (SGI) with the use of visual and semiquantitative interpretation, to compare it with standalone CT analysis, to verify the transferability of the experience with FDG PET/CT in surgical prosthesis infection and to define the role of the method in the diagnostic algorithm of SGI. Subjects and Methods: In this retrospective study, two nuclear medicine physicians have independently analyzed 21 FDG PET/CT examinations performed in 20 subjects (16 men, 66 ± 8 years) between 2010 and 2019 for clinical suspicion of SGI. Six subjects examined from other reasons without signs of infection constituted a control group. The images were evaluated for the uptake pattern and intensity, and by the maximum standard uptake value (SUVmax), the target-to-background ratio with blood pool (TBRBP) and liver uptake (TBRhep) as a reference. The SGI was defined as the presence of focal hyperactivity with an intensity exceeding hepatic uptake. CT images were independently assessed for signs of SGI. Clinical review of all further patients' data served as the standard of reference. Results: Twelve cases were established as SGI by the clinical review. PET/CT correctly diagnosed SGI in eight and yielded a sensitivity of 92 % and...
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陳思吟. "Effectiveness of the Posthorax Sternum Vest on Improving Wound Pain 、Wound Infection and Sleep Quality in the Coronary Artery Graft Surgery Patients". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/fkwym6.
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碩士國立臺北護理健康大學
護理研究所
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Background: Cardiovascular disease is the leading cause of global deaths, accounting for 31% of all deaths, and coronary artery bypass graft surgery is a gold treatment rule of over 70% of coronary artery occlusion in the body. Objectives: The purpose of this study aimed to evaluate the utility of the protective coat with sternal regulator for postoperative patients with coronary artery bypass graft surgery to reduce postoperative acute wound pain as well as chest wound infection, and improve sleep quality. Methodology: The study adopted a quasi-experimental research and collected study cases at a medical center in northern Taiwan for convenient collection. A total of 84 patients were collected by using a structured questionnaire. The questionnaire included the materials as follows: Basic Data Sheet, Numeric Rating Scale (NRS), Brief Pain Inventory-Taiwanese version (BPI-T), ASEPSIS Wound Score for Wound Infection, and VSH Sleep Scale in Chinese version. The research results were obtained through SPSS 22.0 and made statistical analysis with generalized estimating equation (GEE) and descriptive data. Results: The study found that the average age of patients was 61.4 years old, accounting for 77.4% of men. Further, it has no significant difference between the two groups in all basic data. The intervention showed significant differences in the improvement of pain (p < .05) for NRS at 9:00 AM on the fifth day after surgery, at 1:00 PM on the fourth day after surgery, at 5:00 PM on the third day after surgery, while the same situation for BPI-T on the fifth day and on the seventh day after surgery (p < .05). Sleeping problems are common in patients after coronary artery bypass grafts surgery. Regarding the sleeping quality of the intervention group to compare with the control group, no significant difference was recognized for the change extent between before intervention and after any postoperative measurements. The results of VSH Sleep Scale in Chinese version for the two group were 700 scores, which showed that poor postoperative sleeping quality. Moreover, no significant difference was shown in the intervention group for the change extent with ASEPSIS on the third day, fifth day and seventh day as the postoperative measurements, comparing with the control group. According to the results of the study, nurses shall actively assess the condition of pain and sleeping problems of patients with coronary artery bypass graft surgery, timely provide relevant information, and assist patients to recover their physical, psychological, and social functions to the best status through accurate pain assessment and pain control.
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Adassi, Ines. "Evaluating the Antileukemic and Antiviral Activity of TH9402-Photodepleted Peripheral Blood Mononuclear Cells". Thèse, 2018. http://hdl.handle.net/1866/22800.
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Martins, Beatriz Nunes. "Microbial evolution of vascular graft infections in a tertiary hospital : a ten-year analysis on positive graft cultures". Master's thesis, 2020. http://hdl.handle.net/10451/46529.
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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2020Introdução: A infeção protésica vascular é uma complicação grave da cirurgia vascular reconstrutiva. Uma antibioterapia dirigida ao agente infecioso mais provável é essencial para a sua abordagem. A epidemiologia bacteriana e fisiopatologia desta infeção continuam pouco esclarecidas. Este trabalho teve como objetivo analisar o comportamento das infeções protésicas vasculares e os padrões de resistência antimicrobiana da sua flora. Material e métodos: Foi realizado um estudo retrospetivo de dez anos (2008-2018) incluindo todos os doentes admitidos com infeção protésica vascular identificados através culturas de enxerto positivas. Foi efetuada uma extensa análise microbiológica, incluindo a os microorganismos infeciosos, resistência antibiótica e a respetiva prevalência no total e em cada ano de estudo. Resultados: Foram observadas setenta e duas infeções protésicas vasculares em 65 pacientes. A média de idade foi 67 (DP:9.6) anos e 84.6% eram do sexo masculino. A mortalidade associada à infeção foi de10.8%. Catorze doentes foram submetidos bypass aorto-bi-femoral, 13 bypass axilo-femoral, 5 bypass femoro-femoral, 27 bypass femoro-popliteus, 4 endartectomia femoral e angioplastia com patch sintético. A mediana de tempo desde a cirurgia index à infeção foi maior nos enxertos intra-cavitários comparativamente aos extra-cavitários (p=0.011). De todas as infeções, 48 foram monomicrobianas e 24 polimicrobianas. Os agentes gram-negativos foram predominantemente identificados nas infeções intra-cavitárias (53.8%), enquanto nas extracavitárias os agentes gram-positivos foram os mais frequentes (57.7%). As bactérias multiresistentes foram isoladas mais frequentemente nas infeções precoces (p=0.002). Durante o estudo, foi observada uma diminuição dos agentes gram-positivos e um aumento dos gramnegativos, especialmente das espécies extensamente resistentes. Foi observada uma progressão microbiológica semelhante nas infeções nosocomiais do mesmo centro hospitalar. Conclusão: Este estudo demonstrou que a microbiologia das infeções protésicas vasculares varia com a localização do enxerto, com o tempo desde a cirurgia de revascularização e ao longo dos anos, com uma evolução semelhante às infeções nosocomiais do mesmo centro. Estas observações reforçam a importância do estudo da microbiologia de cada centro hospitalar de modo a garantir o melhor tratamento possível destes doentes.
Introduction: Vascular graft infections are a dreadful complication in vascular surgery. Correct antibiotic therapy targeted to the most likely infecting organisms is essential to manage these patients, however bacterial epidemiology and pathogenesis is still not completely understood. We aimed at analyzing the behavior of vascular graft infections and the microbiological patterns of resistance. Material and Methods: We performed a ten-year (2008-2018) retrospective cohort study of all patients admitted with vascular graft infection identified in positive direct graft cultures in our center. An extensive microbiological study was performed analyzing bacterial strains, antibiotic resistance and sensitivity and prevalence according to each year. Results: Seventy-two vascular graft infections with positive graft cultures occurring in 65 patients were found. Mean age was 67 (SD:9.6) years and 84.6% were male. Infection related mortality was 10.8%. Fourteen patients had been submitted to aorto-bi-femoral bypass, 13 to axillo-femoral bypass, 5 to femoro-femoral bypass, 27 to femoro-popliteal bypass, 4 to femoral endarterectomy with synthetic patch angioplasty. The median time from the index procedure to infection was higher in intra-cavitary versus extra-cavitary grafts (p=0.011). Of all infections, 48 were monomicrobial and 24 were polymicrobial. Gram-negative agents were predominantly identified in intra-cavitary graft infections (53.8%) whereas in the extra-cavitary group gram-positive agents were most frequent (57.7%). Multiresistant bacterial agents occurred more frequently in early graft infections (p=0.002). Throughout the duration of the study, an overall decrease in grampositive infections and an increase in gram-negative infections was observed, especially extensively drug resistant strains. A similar progression was found in all nosocomial infections. Conclusion: The present study showed that vascular graft infection microbiology changes according to graft locations, time of infection since revascularization surgery and also evolves over the years with similar patterns as all nosocomial infections. This highlights the importance of studying the specific microbiology of each health center and its relationship with vascular graft infections in order to achieve the best treatment possible.
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Guimarães, Ana Manuela de Sá. "Developing an antimicrobial coating to prevent abdominal aortic graft infections (AGIs)". Master's thesis, 2021. https://hdl.handle.net/10216/137185.
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Pereira, Pedro Henrique Cerqueira. "Ortopaedic bone grafts for prevention of infections and bone regeneration promotion". Master's thesis, 2020. https://hdl.handle.net/10216/130272.
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Pereira, Pedro Henrique Cerqueira. "Ortopaedic bone grafts for prevention of infections and bone regeneration promotion". Dissertação, 2020. https://hdl.handle.net/10216/130272.
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