This research focuses on the utilization of two living polymerization methods, anionic and group transfer, for the synthesis of well defined end functional materials and graft copolymers. Group transfer polymerization was utilized to synthesize acrylic terminal poly(methyl methacrylate) (PMMA) macromonomers of controlled molecular weight and narrow molecular weight distribution. A systematic series of PMMA macromonomers were copolymerized with 2-ethylhexyl acrylate to afford poly(2-ethylhexyl-g-methyl methacrylate) copolymers. These copolymers were synthesized in high yields with a high degree of incorporation of the PMMA macromonomer. These graft copolymers showed little or no phase mixing between the two components as evidenced by differential scanning calorimetry. It was determined by optimization studies that the reaction was complete within 50 hours at 65° C. Increases in initiator concentration surprisingly did not significantly effect homopolymerizations of 2-ethylhexyl acrylate with respect to molecular weight while the efficiency of incorporation of the macromonomer into the graft copolymers increased. End functional hydrogenated poly(butadiene) (HPBd) materials and HPBd-containing graft copolymers were synthesized using anionic polymerization methods. These materials were tested for their ability to act as adhesion promoters between poly(propylene)/EPDM and cycloaliphatic polyurethane coatings. Hydroxyl or carboxyl end functional materials were synthesized where molecular weight and chain microstructure were syStematically varied. Effective adhesion was achieved when the molecular weight of the polymer was approximately 20 kg/mol, the polymer was hydrogenated, contained 90 mole percent or greater 1,2- content in the poly(butadiene) precursor, and contained a functional end group, which may be either hydroxyl or carboxyl. To increase the concentration of functional groups over the above materials graft copolymers were utilized. Acrylic terminal HPBd macromonomers were synthesized and copolymerized with butyl acrylate in combination with either N,N-dimethylacrylamide (DMAA), 2-hydroxyethyl methacrylate (HEMA), methacrylic acid (MA), or t-butyl methacrylate (TBMA). Systematic compositions of these graft copolymers were synthesized and tested for adhesion. The acidic containing graft copolymers provided the most positive adhesion results. In one case the hydroxyl containing material also gave positive adhesion results. The DMAA containing materials failed in all cases. The TBMA route allowed for greater control over the composition of the acidic graft copolymers. / Ph. D.

Poly[bis(2,2,2-trifluoroethoxyphosphazene)]-polystyrene graft copolymers were synthesized by a “grafting onto" reaction which involved a reaction between two preformed, reactive polymer chains. In this case, poly(dichlorophosphazene) was the reactive polymer backbone onto which approximately 10 weight percent polystyrene chains were grafted. In order to avoid chain degradation of the poly(dichlorophosphazene), the polystyryl lithium chains were modified by the addition of ethylene oxide. This reaction introduced -CH₂CH₂O⁻Li⁺ groups on the chain ends and rendered them a more suitable nucleophile. Remaining chlorine sites along the poly(dichlorophosphazene) backbone were substituted with 2,2,2-trifluoroethoxy groups. The grafting reaction proceeded with and without the catalyst, tetrabutylammonium bromide. This reagent acted as an ion separation catalyst and seemed to increase the reactivity and ionic character of the O⁻Li⁺ bond. This was evident with respect to reaction times. The catalyst decreased reaction times from several days for the uncatalyzed reaction to ~30 hours for the catalyzed reaction. Difficulties in characterization of the poly[bis(2,2,2-trifluoroethoxyphosphazene)]-polystyrene graft copolymers were encountered. DSC analysis of both the graft copolymer and homopolymer physical blends seemed to indicate partial compatibility between the polystyrene and poly[bis(2,2,2-trifluoroethoxyphosphazene)] components. Infrared and ultraviolet spectroscopy revealed the presence of polystyrene in the graft copolymer system; however, these results were difficult to verify due to the possibility of polystyrene homopolymer contamination. Calculation of the number of polystyrene chains grafted onto the polyphosphazene backbone were hampered by resultant insolubility of the graft copolymer system. / M.S.

Coronary artery bypass graft (CABG) är en väl etablerad behandling för patienter med kranskärlssjukdom. Operationen är utmanande och påfrestande för patienten och upplevelserna efter genomgången operation är varierade. Att som sjuksköterska ha kännedom om patienters upplevelser tiden efter operationen är av betydelse för att möjliggöra god omvårdnad och återhämtning för patienten. Syftet var att belysa patienters upplevelser tiden efter en CABG. Studien grundades på 11 vetenskapliga artiklar och genomfördes som en litteraturstudie. Fyra teman framkom i resultatet; den relationella upplevelsen, den kroppsliga upplevelsen, den mentala skörheten och en ny syn på livet. Det framkom att patienterna upplevde stödet från omgivningen som det viktigaste för god återhämtning. Information från vårdpersonalen ansågs till viss del bristfällig av patienterna. Flera upplevde smärta efter operationen och hade delvis symtom kvar, men dessa avtog med tiden. Centralt efter operationen var även oro, men med tiden kom förbättrad livskvalitet och motivation. Det framkom att en CABG var en stor påfrestning för patienten och upplevelserna var både positiva och negativa. Kunskapsluckor avseende patientupplevelser efter operationen finns och ytterligare forskning bör fokusera på området för att ge sjuksköterskestudenter och sjuksköterskor ökad kunskap i mötet med denna patientgrupp. / Coronary artery bypass graft (CABG) is a well-established treatment for patients with coronary artery disease. The surgery is challenging and stressful for the patient and experiences varied after surgery. It’s important for the nurse to be aware of patients’ experiences after surgery to enable good care and recovery for the patient. The aim was to illuminate patients’ experiences during the time after a CABG. The study was based on 11 scientific articles and was conducted as a literature review. Four themes emerged; the relational experience, the bodily experience, the mental fragility and a new view on life. The result showed that patients' experienced the support from the surroundings as the most important for good recovery. Information given by caregivers were in some cases considered inadequate by the patients. Patients experienced pain after surgery and had partial symptoms left, which subsided with time. Concern was a central experience after surgery, but over time came improved quality of life and motivation. A CABG is a major strain for the patients and the experiences were both positive and negative. There are gaps in knowledge regarding patient experiences after the surgery and further research should focus on that area to give nursing students and nurses knowledge in the meeting with these patients.

Advances in haploidentical bone marrow transplantation (h-BMT) have drastically broadened the treatment options for patients requiring BMT. The possibility of significantly reducing the complications resulting from graft-versus-host disease (GvHD) with the administration of post-transplant cyclophosphamide (PT-CY) has substantially improved the efficacy and applicability of T cell-replete h-BMT. However, higher frequency of disease recurrence remains a major challenge in h-BMT with PT-CY. There is a critical need to identify novel strategies to prevent GvHD while sparing the graft-versus-leukaemia (GvL) effect in h-BMT. To this end, we evaluated the impact of bendamustine (BEN), given post-transplant, on GvHD and GvL using clinically relevant murine h-BMT models. We provide results indicating that post-transplant bendamustine (PT-BEN) alleviates GvHD, significantly improving survival, while preserving engraftment and GvL effects. We further document that PT-BEN can mitigate GvHD even in the absence of Treg. Our results also indicate that PT-BEN is less myelo-suppressive than PT-CY, significantly increasing the number and proportion of CD11b(+)Gr-1(hi) cells, while decreasing lymphoid cells. In vitro we observed that BEN enhances the suppressive function of myeloid-derived suppressor cells (MDSCs) while impairing the proliferation of T-and B-cells. These results advocate for the consideration of PT-BEN as a new therapeutic platform for clinical implementation in h-BMT.

In patients undergoing hematopoietic stem cell transplantation (HSCT) with HLA-identical donors, genetic polymorphisms result in a mismatch between donors and recipients in their minor histocompatibility antigens (mHAgs), and tumors may also express tumor-associated antigens (TAA) that may not be abundantly present in the donors. Donor T cells can recognize such mHAgs and TAAs as foreign antigens and generate an objective response against hematologic malignancies in a graft-versus-tumor (GVT) effect. However, a major side effect of HSCT occurs when donor T cells are alloreactive against the recipients’ normal cells, leading to graft-versus-host disease (GVHD). The ability to identify T cell clones that are exclusively involved in the GVT or GVHD responses remains elusive. In this study, we looked at clonally-driven CD3+ T cells in patients with hematologic malignancies prior to and after transplantation. We identified Vbeta families of increased expression involved in GVHD or GVT responses, with Vbetas 4, 11, and 23 being associated with GVHD, Vbetas 9, 16, and 20 being associated with GVT, and Vbetas 2, 3, 7, 8, 12, 15, and 17 being involved in GVHD and/or GVT. We were also able to identify some of the Vbeta families that were increased in the peripheral blood at the site of GVHD. Furthermore, one of our twelve patients had donor lymphocyte infusions (DLIs) for treatment of relapse, from which we were able to observe oligoclonal T cells that emerged at the time of post-DLI remission and re-establishment of GVHD.

Introdução: O transplante cardíaco exerce um papel relevante no tratamento da insuficiência cardíaca grave. Dentro dos desfechos desfavoráveis a seus resultados, a falência primária do enxerto é reconhecida, como condição de gravidade e mortalidade elevada. Os fatores implicados no aparecimento da falência primária do enxerto ainda não são bem esclarecidos e sua relevância é pouco estudada. Objetivo: Observar se há associação entre hipernatremia do doador e de outras variáveis com o desenvolvimento da falência primária do enxerto (FPE). Métodos: Foram avaliados, retrospectivamente, 200 pacientes submetidos à cirurgia de Transplante Cardíaco Ortotópico (TxC) no Instituto Dante Pazzanese de Cardiologia (IDPC), no período entre 01/01/2001 e 31/12/2010, sendo cotado os níveis de sódio sérico no doador. Além disto, foram avaliados outros fatores relacionados ao doador, ao receptor e ao procedimento cirúrgico. Após a identificação de que o sódio sérico do doador estava elevado no grupo de receptores com FPE, um ponto de corte foi obtido pela curva ROC. O nível de significância dos testes foi de 5%. Um modelo de regressão logística múltipla foi ajustado para avaliar os efeitos de fatores e covariáveis presentes na FPE. Resultados: Entre os pacientes que desenvolveram falência primária do enxerto, a média do sódio sérico foi de 162,0 mEq/l contra 153,6 mEq/l dos que não apresentaram FPE. O valor de corte pela curva ROC foi de 159 mEq/l. Houve diferença significativa (p< 0,03) entre os dois grupos com aumento de ocorrência de falência primária do enxerto nos pacientes que receberam órgãos oriundos de doadores com sódio sérico >159mEq/l. A outra variável que apresentou valor significativo (p=0,04) foi o tabagismo do doador. Conclusão: Com base nesses achados, observou-se que existe associação entre a elevação do sódio sérico do doador com o desenvolvimento de falência primária do enxerto, após o transplante cardíaco. / Introduction: Cardiac transplantation has a role in the treatment of severe heart failure. Within the unfavorable outcomes to their results, the primary graft failure is recognized as a condition of severity and high mortality. The factors involved in the onset of primary graft failure are still unclear and their relevance is poorly studied. Objective: Observe if there is an association between donor hypernatremia and other variables with the development of primary graft failure (PGF). Methods: We retrospectively evaluated 200 patients who underwent surgery for orthotropic heart transplantation (HT) at the Instituto Dante Pazzanese de Cardiologia (IDPC) in the period between 01/01/2001 and 12/31/2010, and evaluated the serum sodium levels in the donor. Furthermore, we assessed other factors related to the donor, the recipient and the surgical procedure. After identification that the donor serum sodium was higher in the group of receivers with PGF, a cutoff point was obtained by ROC curve. The level of significance of the tests was 5%. A multiple logistic regression model was fitted to assess the effects of factors and covariates present in PGF. Results: Among patients who developed primary graft failure, the mean serum sodium was 162.0 mEq/l versus 153.6 mEq/l of which showed no PGF. The cutoff value for the ROC curve was 159 mEq/l. There was an important difference (p <0.03) between the two groups with increased incidence of primary graft failure in patients who received organs from donors with serum sodium> 159 mEq/l. The other variable that showed a significant value (p = 0.04) was smoking from the donor. Conclusion: Based on these findings, we observed that there is an association between elevated serum sodium from the donor with the development of primary graft failure after heart transplantation.

Foi estudado experimentalmente o desempenho biológico de um tipo de enxerto ósseo homógeno, processado quimicamente, esterilizado em óxido de etileno e embebido em medula óssea autógena. De cães doadores adulto-jovens foram obtidos blocos cilíndricos de 1,0 x 1,0 cm da epífise distal do fêmur, com auxílio de uma trefina. Os ossos assim obtidos foram clareados, desengordurados, esterilizados em óxido de etileno e mantidos em estoque. Trinta cães adultos jovens foram usados como receptores do enxerto e foram alocados em dois grupos. No grupo I (experimental) os animais foram operados e, criado, transversalmente, com trefina de 1,0 cm de diâmetro externo, um espaço cilíndrico de 1,0 cm de diâmetro por 1,0 cm de altura na epífise distal do fêmur direito, onde foi encaixado o enxerto preparado e que foi previamente embebido em medula óssea do próprio animal retirada por punção óssea na crista ilíaca. Três semanas depois, o mesmo animal foi submetido ao mesmo procedimento cirúrgico no fêmur esquerdo. Os cães deste grupo foram sacrificados seis semanas após a primeira cirurgia. O grupo II constituiu o controle e foi formado por vinte cães adulto-jovens em que, primeiro, foi retirado um cilindro de osso da epífise distal do fêmur esquerdo e, em seguida, no mesmo tempo cirúrgico, foi criado o mesmo espaço no fêmur direito, com uma trefina de um centímetro de diâmetro interno e, então, encaixado o bloco de osso retirado do fêmur do outro lado do mesmo animal. Estes animais foram subdivididos em dois subgrupos de dez cães cada, em relação ao tempo de sacrifício. Em um subgrupo os cães foram sacrificados três semanas após, enquanto que, no outro subgrupo, foram sacrificados seis semanas após a cirurgia de implantação do enxerto. O processo de incorporação do enxerto foi avaliado pela histologia convencional e histologia de fluorescência óssea, pela injeção prévia de tetraciclina. A comparação foi entre os grupos I e II, nos períodos de três e seis semanas pós-implante. As áreas dos enxertos homógenos com 21 dias pós-implante, geralmente mostraram-se visíveis, na maioria das vezes, formadas por trabéculas finas irregulares, sem osteócitos, porém com áreas de neoformação óssea. Já os enxertos autógenos, a área do osso implantado era bem visível, com trabéculas de osso antigo, mais adelgaçadas, em menor número que o osso receptor, porém com intensa deposição de osso neoformado. Para os enxertos homógenos com 42 dias pós-implante, a área do enxerto estava bem definida e integrada ao osso adjacente, composta por trabéculas antigas com predomínio de osso neoformado sobre a superfície. Nos enxertos autógenos com 42 dias pós-implante, as trabéculas tinham orientação comum, com espaço intertrabecular preenchido por tecido conjuntivo denso, em algumas áreas, e por medula óssea madura em outras. O enxerto homógeno processado e esterilizado em óxido de etileno e embebido em medula óssea apresentou boa atividade biológica, embora, com integração mais lenta e menor desempenho em relação ao enxerto autógeno, o que o torna um bom substituto para este último. / In the present investigation the biological performance of the homogenous bone graft chemically processed, sterilized with ethylene oxide and soaked in autogenous bone marrow was investigated. Thirty dogs were assigned into two groups. In group I, ten young adult dogs received a cylindrical block of the above mentioned graft. Previously, the bone graft was immersed in autogenous bone marrow and then inserted in a cylindrical hole, with the same dimensions, created at the distal femoral epiphysis of the right femur. After three weeks the same animal was submitted to the same surgical procedure, but on the left femur. The animal was killed six weeks later. The group II was made up of twenty dogs that received an autogenous graft obtained from the left distal femur and implanted into the right distal femur (same shape, dimensions and technique). From this group, 10 dogs were killed three weeks later and 10 dogs were killed six weeks later. The graft incorporation was evaluated by light microscopy and fluorescence microscopy. Results showed that for 21 day implant in the homogenous group, there was osteogenesis at the periphery of the bone graft, but most of its trabeculae were still inviable. Conversely, for the autogenous grafts newly-formed bone was found on the trabecular surface, even in the inner parts of the implanted bone. At 42 days there was active osteogenesis in homogenous grafts with new bone deposition on the trabeculae but, in two cases, the graft was not incorporated (reabsorbed in one case and sequestred in the other one). The autogenous graft showed newly formed bone arranged in a well mature fashion with new bone marrow filling the intertrabecular gaps. It was concluded that the homogenous graft as prepared herein is a good alternative for autogenous grafts, although with a slower osteogenesis rate an less biological performance.

Thesis ( M.Sc.). / Written for the Dept. of Epidemiology and Biostatistics. Title from title page of PDF (viewed 2008/05/29). Includes bibliographical references.

Introdução: O transplante cardíaco exerce um papel relevante no tratamento da insuficiência cardíaca grave. Dentro dos desfechos desfavoráveis a seus resultados, a falência primária do enxerto é reconhecida, como condição de gravidade e mortalidade elevada. Os fatores implicados no aparecimento da falência primária do enxerto ainda não são bem esclarecidos e sua relevância é pouco estudada. Objetivo: Observar se há associação entre hipernatremia do doador e de outras variáveis com o desenvolvimento da falência primária do enxerto (FPE). Métodos: Foram avaliados, retrospectivamente, 200 pacientes submetidos à cirurgia de Transplante Cardíaco Ortotópico (TxC) no Instituto Dante Pazzanese de Cardiologia (IDPC), no período entre 01/01/2001 e 31/12/2010, sendo cotado os níveis de sódio sérico no doador. Além disto, foram avaliados outros fatores relacionados ao doador, ao receptor e ao procedimento cirúrgico. Após a identificação de que o sódio sérico do doador estava elevado no grupo de receptores com FPE, um ponto de corte foi obtido pela curva ROC. O nível de significância dos testes foi de 5%. Um modelo de regressão logística múltipla foi ajustado para avaliar os efeitos de fatores e covariáveis presentes na FPE. Resultados: Entre os pacientes que desenvolveram falência primária do enxerto, a média do sódio sérico foi de 162,0 mEq/l contra 153,6 mEq/l dos que não apresentaram FPE. O valor de corte pela curva ROC foi de 159 mEq/l. Houve diferença significativa (p< 0,03) entre os dois grupos com aumento de ocorrência de falência primária do enxerto nos pacientes que receberam órgãos oriundos de doadores com sódio sérico >159mEq/l. A outra variável que apresentou valor significativo (p=0,04) foi o tabagismo do doador. Conclusão: Com base nesses achados, observou-se que existe associação entre a elevação do sódio sérico do doador com o desenvolvimento de falência primária do enxerto, após o transplante cardíaco. / Introduction: Cardiac transplantation has a role in the treatment of severe heart failure. Within the unfavorable outcomes to their results, the primary graft failure is recognized as a condition of severity and high mortality. The factors involved in the onset of primary graft failure are still unclear and their relevance is poorly studied. Objective: Observe if there is an association between donor hypernatremia and other variables with the development of primary graft failure (PGF). Methods: We retrospectively evaluated 200 patients who underwent surgery for orthotropic heart transplantation (HT) at the Instituto Dante Pazzanese de Cardiologia (IDPC) in the period between 01/01/2001 and 12/31/2010, and evaluated the serum sodium levels in the donor. Furthermore, we assessed other factors related to the donor, the recipient and the surgical procedure. After identification that the donor serum sodium was higher in the group of receivers with PGF, a cutoff point was obtained by ROC curve. The level of significance of the tests was 5%. A multiple logistic regression model was fitted to assess the effects of factors and covariates present in PGF. Results: Among patients who developed primary graft failure, the mean serum sodium was 162.0 mEq/l versus 153.6 mEq/l of which showed no PGF. The cutoff value for the ROC curve was 159 mEq/l. There was an important difference (p <0.03) between the two groups with increased incidence of primary graft failure in patients who received organs from donors with serum sodium> 159 mEq/l. The other variable that showed a significant value (p = 0.04) was smoking from the donor. Conclusion: Based on these findings, we observed that there is an association between elevated serum sodium from the donor with the development of primary graft failure after heart transplantation.

Foi estudado experimentalmente o desempenho biológico de um tipo de enxerto ósseo homógeno, processado quimicamente, esterilizado em óxido de etileno e embebido em medula óssea autógena. De cães doadores adulto-jovens foram obtidos blocos cilíndricos de 1,0 x 1,0 cm da epífise distal do fêmur, com auxílio de uma trefina. Os ossos assim obtidos foram clareados, desengordurados, esterilizados em óxido de etileno e mantidos em estoque. Trinta cães adultos jovens foram usados como receptores do enxerto e foram alocados em dois grupos. No grupo I (experimental) os animais foram operados e, criado, transversalmente, com trefina de 1,0 cm de diâmetro externo, um espaço cilíndrico de 1,0 cm de diâmetro por 1,0 cm de altura na epífise distal do fêmur direito, onde foi encaixado o enxerto preparado e que foi previamente embebido em medula óssea do próprio animal retirada por punção óssea na crista ilíaca. Três semanas depois, o mesmo animal foi submetido ao mesmo procedimento cirúrgico no fêmur esquerdo. Os cães deste grupo foram sacrificados seis semanas após a primeira cirurgia. O grupo II constituiu o controle e foi formado por vinte cães adulto-jovens em que, primeiro, foi retirado um cilindro de osso da epífise distal do fêmur esquerdo e, em seguida, no mesmo tempo cirúrgico, foi criado o mesmo espaço no fêmur direito, com uma trefina de um centímetro de diâmetro interno e, então, encaixado o bloco de osso retirado do fêmur do outro lado do mesmo animal. Estes animais foram subdivididos em dois subgrupos de dez cães cada, em relação ao tempo de sacrifício. Em um subgrupo os cães foram sacrificados três semanas após, enquanto que, no outro subgrupo, foram sacrificados seis semanas após a cirurgia de implantação do enxerto. O processo de incorporação do enxerto foi avaliado pela histologia convencional e histologia de fluorescência óssea, pela injeção prévia de tetraciclina. A comparação foi entre os grupos I e II, nos períodos de três e seis semanas pós-implante. As áreas dos enxertos homógenos com 21 dias pós-implante, geralmente mostraram-se visíveis, na maioria das vezes, formadas por trabéculas finas irregulares, sem osteócitos, porém com áreas de neoformação óssea. Já os enxertos autógenos, a área do osso implantado era bem visível, com trabéculas de osso antigo, mais adelgaçadas, em menor número que o osso receptor, porém com intensa deposição de osso neoformado. Para os enxertos homógenos com 42 dias pós-implante, a área do enxerto estava bem definida e integrada ao osso adjacente, composta por trabéculas antigas com predomínio de osso neoformado sobre a superfície. Nos enxertos autógenos com 42 dias pós-implante, as trabéculas tinham orientação comum, com espaço intertrabecular preenchido por tecido conjuntivo denso, em algumas áreas, e por medula óssea madura em outras. O enxerto homógeno processado e esterilizado em óxido de etileno e embebido em medula óssea apresentou boa atividade biológica, embora, com integração mais lenta e menor desempenho em relação ao enxerto autógeno, o que o torna um bom substituto para este último. / In the present investigation the biological performance of the homogenous bone graft chemically processed, sterilized with ethylene oxide and soaked in autogenous bone marrow was investigated. Thirty dogs were assigned into two groups. In group I, ten young adult dogs received a cylindrical block of the above mentioned graft. Previously, the bone graft was immersed in autogenous bone marrow and then inserted in a cylindrical hole, with the same dimensions, created at the distal femoral epiphysis of the right femur. After three weeks the same animal was submitted to the same surgical procedure, but on the left femur. The animal was killed six weeks later. The group II was made up of twenty dogs that received an autogenous graft obtained from the left distal femur and implanted into the right distal femur (same shape, dimensions and technique). From this group, 10 dogs were killed three weeks later and 10 dogs were killed six weeks later. The graft incorporation was evaluated by light microscopy and fluorescence microscopy. Results showed that for 21 day implant in the homogenous group, there was osteogenesis at the periphery of the bone graft, but most of its trabeculae were still inviable. Conversely, for the autogenous grafts newly-formed bone was found on the trabecular surface, even in the inner parts of the implanted bone. At 42 days there was active osteogenesis in homogenous grafts with new bone deposition on the trabeculae but, in two cases, the graft was not incorporated (reabsorbed in one case and sequestred in the other one). The autogenous graft showed newly formed bone arranged in a well mature fashion with new bone marrow filling the intertrabecular gaps. It was concluded that the homogenous graft as prepared herein is a good alternative for autogenous grafts, although with a slower osteogenesis rate an less biological performance.