Bakgrund: I Sverige genomförs ca 700 organtransplantationer årligen. Organ kan doneras från levande och avliden donator. Antalet möjliga donatorer har ökat men är inte tillräckligt för att tillgodose behovet. Att vänta på ett organ innebär stor ovisshet och leder till att relationer förändras. Personerna känner hopp och är förväntansfulla inför livet efter transplantationen. Personer som är levande donatorer ångrar inte sitt beslut att donera efteråt. Sjuksköterskor som arbetar med patienter som väntar på en organtransplantation skapar en nära relation till patienten, arbetet kan vara mycket psykiskt påfrestande men också givande.  Syfte: Att beskriva personers upplevelser efter en organtransplantation.  Metod: Beskrivande litteraturstudie baserat på 10 kvalitativa artiklar.  Resultat: Första tiden efter en organtransplantation upplever personerna isolering och begränsningar. Oro för avstötning och för framtiden förekommer och personerna anpassar sig på olika sätt. Personerna upplever brist på förståelse, svårigheter att leva upp till förväntningar och beskriver behov av stöd. Relationen till familj och vänner förändras. Känslor av tacksamhet och skuld har betydelse.  Slutsats: Tiden efter en organtransplantation upplevs isolerande och kantas av känslor som oro, tacksamhet och skuld. Personerna behöver göra anpassningar genom en förändrad livsstil och upplever en ny vardag. Det är svårt att leva upp till andras förväntningar, relationer förändras och personer upplever brist på förståelse och ett behov av stöd. Att hjälpa personerna se mening i sina upplevelser, och att styra de hälsofrämjande insatserna till att stödja personernas egna förmågor och resurser är en viktig del av sjuksköterskans arbete. / Background: Approximately 700 organ transplantations are undertaken in Sweden every year. Organs can be donated from both living and deceased donors. The number of possible donors has increased but is not enough to accommodate the need. Waiting for an organ means living with great uncertainty. It also changes relationships with family and friends. People waiting for an organ are hopeful for the future and are anticipating normalcy after the transplantation. Living donors do not regret their decision to donate. Nurses caring for people waiting for an organ establish close relations to the patient, their work can be mentally demanding but also rewarding.  Aim: To describe people´s experiences after an organ transplantation.  Method: Descriptive literature review based on 10 qualitative articles.  Result: Time after an organ transplantation is experienced as isolating and restrictive. There are experiences of anxiety of organ rejection and worry about the future and people adapt in different ways. People feel a lack of understanding from others and find it hard to meet expectations. There is a need for support and relations alter. Feelings of gratitude and guilt are of significance.  Conclusion: Time after an organ transplantation is isolating and there are feelings of anxiety, gratitude and guilt. People adapt by making lifestyle changes and experiences a new living. Meeting others expectations is difficult and relationships alter. People experiences lack of understanding and need for support. Helping people find meaning in their experiences and guiding them to use their abilities and resources is an important aspect of nursing.

惡性腫瘤嚴重威脅著人類的身體健康，其治療也成為人類關注的焦點。傳統的化學療法和放射療法由於缺乏特異性，取得療效的同時往往也帶來較大的毒副作用。隨著對腫瘤發生發展分子機制認識的不斷深入，腫瘤的基因治療已成為攻克和治愈腫瘤最具希望和挑戰的研究領域。近年來研究發現骨髓間充斥幹細胞(MSCs)可被募集至腫瘤或損傷部位并參與腫瘤生長或組織修復，研究證明間充斥幹細胞通過靜脈注入帶瘤鼠（比如乳腺癌、膠質瘤、結腸癌及黑色素瘤）體內后，特異性的分佈于生長中的腫瘤中。這種特異性向腫瘤組織趨化轉移的特性使得骨髓間充斥幹細胞成為腫瘤基因靶向治療的載體的理想細胞。酶蛋白基因如單純皰疹病毒胸苷激酶(HSV-TK)可以使一些無毒或低毒的前藥轉化為強細胞毒性物質，殺死腫瘤細胞。我們前期實驗結果表明，通過遺傳改造后的表達TK基因的MSCs在GCV的存在下，具有殺傷腫瘤細胞抑制腫瘤生長的能力。但沒有改造的MSCs遷移至腫瘤之後可能會分化成成纖維細胞或者腫瘤基質細胞等支持腫瘤生長，但其命運和影響到底如何，我們怎麼樣進一步促進其向腫瘤的遷移以提高殺傷腫瘤的效率是本研究需要解決的問題。 / 本研究擬採用免疫螢光組織化學技術和分子生物學等技術研究和觀察MSCs對腫瘤（以乳腺癌，前列腺癌為例）的趨化過程及其在腫瘤生長中的作用，在在此基礎上研究促進攜帶HSV-TK自殺基因的MSCs的腫瘤靶向性細胞治療策略，採用分子和細胞生物學等方法評估其對荷瘤鼠體內腫瘤殺傷的原理，為利用TK-MSCs腫瘤的靶向治療奠定基礎。 / 研究結果顯示體外共培養的條件下，小鼠骨髓間充斥幹細胞可促進小鼠乳腺癌細胞增長，且增長速度同培養體系中間充斥幹細胞數目呈正相關。將兩種細胞混合注射于裸鼠體內，相比共注射小鼠皮膚成纖維細胞，間充斥幹細胞可促進體內腫瘤生長。使用人胚胎骨髓間充斥幹細胞和前列腺癌細胞可得出類似的效果。將腫瘤組織切片分析發現間充斥幹細胞促進體內腫瘤細胞增殖的同時，提高了腫瘤組織內血管密度。體外實驗發現共培養前列腺癌細胞和間充斥幹細胞可促進血管生成且在間充斥細胞內同血管增生相關的蛋白表達量都有相應提高，進一步證實間充斥幹細胞可能通過促進血管增生從而促進腫瘤生長。另外，我們利用人胚胎來源的骨髓間充斥幹細胞建立了穩定表達TK自殺基因的細胞系，且在GCV的存在下具有抑制腫瘤生長的能力。為了促進它們向腫瘤遷移的能力，我們用多柔比星預處理腫瘤細胞，和沒處理過的對照組相比，能增強對表達TK的間充斥幹細胞的招募能力。且在聯合利用多柔比星和TK的條件下，腫瘤生長能得到較大程度的抑制，這種抑制作用强於單獨使用多柔比星和表達自殺基因的間充斥幹細胞系統。初步認為是多柔比星的處理能增強腫瘤組織內炎性介質的分泌從而增強間充斥幹細胞的遷移達到增強自殺基因系統殺死腫瘤細胞的目的。 / 總的來說，雖然間充質幹細胞對腫瘤的生長存在一定的促進作用，但我們仍能對其進行遺傳改造，且在其它抗腫瘤藥的配合下達到最大的抗腫瘤效果。 / Eradication of cancer, especially when it has metastasized is extremely difficult and conventional cancer therapies are simply unable to specifically target tumors/cancers, thus causing unwanted side effects and complications. Recently, it has been shown that bone marrow mesenchymal stem cells (MSCs) are able to migrate specifically to tumors and contribute to the formation of tumor-associated stroma. These properties make MSCs good candidates as anti-tumor agent delivery vehicles and lead to a great deal of interest in the possibility of genetically modifying MSCs to express anticancer molecules and using them as specific targeted anticancer agents. We and others have showed that MSCs have the ability to migrate towards various cancer cells including breast, colon, fibrosarcoma and prostate cancer cells. Suicide gene therapy is widely used in cancer gene therapy. When stably infected with herpes simplex virus thymidine kinase gene by lentivirus, TK-MSCs maintained their MSCs characters and tumor tropism potential and significantly inhibited tumor growth, in the presence of the pro-drug ganciclovir (GCV). Improve MSCs homing to tumor tissue as anti-tumor gene therapy vehicles and maximizing their tumor killing effects is highly warranted. Furthermore, MSCs interact with tumor cells in numerous ways, which have the potential to support or suppress tumor growth. Therefore the fate and role of MSCs engrafted in tumor sites need to be clarified in order to making better use of these cells as anti-cancer agent delivery vehicles. / The aims of the current study are: (1) to study the role and fate of MSCs homed into the tumors; (2) to establish human bone marrow MSCs that stably express the TK genes; (3) to investigate the methods that enhance the anti-tumor efficiency of TK-MSCs. / In this study, bone marrow-derived mesenchymal stem cells from mice or human fetus were isolated and characterized. Effects of BM-MSCs on tumor cell proliferation in vitro were analyzed in a co-culture system with mouse breast cancer cell 4T1 cells. Both co-culture with BM-MSCs and treatment with MSC-conditioned medium led to enhanced growth of 4T1 cells. Co-injection of 4T1 cells and MSCs into nude mice led to increased tumor size compared with injection of 4T1 cells alone. Identical experiments using human prostate cancer cell DU145 cells and hBM-MSCs instead of 4T1 cells and mBM-MSCs yielded similar results. Compared with tumors induced by injection of cancer cells alone, tumor vessel area was greater in tumors from co-injection of 4T1 or DU145 with BM-MSCs, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. Furthermore, both conditioned medium from co-cultures of hBM-MSCs and DU145 cells or hBM-MSCs alone was able to induce angiogenesis in human umbilical vein endothelial cells (HUVEC). When hBM-MSCs exposed to DU145 cells environment, the expression of markers associated with neovascularization (α-SMA, VEGF, TGF-β and IL6) were increased. Together, these results indicate that MSCs promote tumor growth both in vitro and in vivo and suggest that tumor promotion in vivo may be attributable in part to enhanced angiogenesis. / Immortalized human fetal bone marrow-derived MSCs (hfBMSCs) expressing herpes simplex virus thymidie kinase was established by conventional lentiviral transduction method. Functional expression of TK was evaluated by cytotoxicity in the presence of its prodrug GCV. SV40-TK-hfBMSCs exhibited comparable proliferation, surface phenotype expression, multi-differentiation potential and tumor-tropic migration ability as hfBMSCs. By measurement of tumor volume, repeated injection of the SV40-TK-hfBMSCs and subsequent consecutive GCV administration could suppress tumor growth in DU145 or PC3 human prostate tumor xenograft nude mice model without causing weight loss. However, its clinical applications are still limited. Alternative strategies have been pursued in this study by the use of combination therapy with cytotoxic chemotherapy to improve the overall efficacy of the TK-hfBMSCs/GCV system. / TK-hfBMSCs/GCV was evaluated alone or combined with low-dose doxorubicin in human prostate carcinoma DU145 xenografts in nude mice, testing for effects on local growth and overall survival. Tissues were evaluated through immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining (TUNEL) for treatment effects on tumor cell proliferation and apoptosis. Transwell migration assay was used to access the migration ability of TK-hfBMSCs to tumor cells upon doxorubicin treatment and caspase-3 activity was conducted for test the tumor cells apoptosis under TK-hfBMSCs/GCV, doxorubicine, or combination of the two compound treatments respectively. Only minimal growth inhibition was observed in DU145 after treatment with TK-hfBMSCs/GCV or doxorubicin alone at doses and time points as indicated. In contrast, the combination of both agents resulted in a significant growth inhibition. Caspase-3, plays a central role in the execution-phase of cell apoptosis, was increased by TK-hfBMSCs/GCV or doxorubicine and also to a much greater extent by the combination treatment. Treatment by TK-hfBMSCs/GCV resulted in only a slight decrease in tumor growth compared with controls. Treatment with low-dose doxorubicin alone resulted in a small, nonstatistically significant decrease in tumor growth; In contrast, combined low-dose doxorubicin and TK-hfBMSCs/GCV was markedly inhibitory compared with control, doxorubicin alone, or TK-hfBMSCs/GCV alone. During the whole treatment process, no significant weight loss was observed. Furthermore, combined therapy induced increased area of necrosis, significant apoptosis and decreased tumor cell proliferation in treated tumors. Taken together, low dosage of doxorubicin could be used in combination with TK-hfBMSCs based suicide gene therapy. / In conclusion, we have demonstrated that BM-MSCs could increase the growth of human prostate cancer and mouse breast cancer. The promotion effect may partly attribute to the increased expression of pro-angiogenic factors in BM-MSCs in tumor microenvironment and subsequent enhancement in angiogenesis and tumor growth. The current study also suggests combination of TK-hfBMSCs/GCV and doxorubicin was more effective in inhibiting prostate cancer cells growth than TK-hfBMSCs/GCV or doxorubicin alone. Although many problems need to be resolved for further application, our study provided the possibility of a new strategy of suicide gene-based therapy accompanied by low dosage of chemotherapy in treating prostate cancer. Therefore MSCs were described as a “double-edged sword in their interaction with tumors. However, if MSCs are suitably engineered with anticancer genes they could be employed as a valuable “single-edged sword“ against cancers. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Zhang, Ting. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 120-158). / Abstracts also in Chinese. / ACKNOWLEDGEMENT --- p.ii / PUBLICATIONS --- p.vii / ABSTRACT --- p.xiii / Chapter CHAPTER 1 --- Introduction --- p.1 / Chapter 1.1 --- Mesenchymal stem cells (MSCs) --- p.2 / Chapter 1.2 --- Tumor microenvironment and involvement of MSCs in tumor establishment --- p.5 / Chapter 1.3 --- Tumors-tropic characteristics of MSCs --- p.15 / Chapter 1.4 --- Impact of MSCs on in vivo tumors --- p.21 / Chapter 1.5 --- In vivo imaging demonstrating MSCs tumor-homing potentials --- p.25 / Chapter 1.6 --- Evidence for use of MSCs as anti-tumor agents delivery vehicles --- p.26 / Chapter 1.7 --- Homing strategies to enhance efficacy and safety of MSCs therapy --- p.32 / Chapter 1.8 --- Summary --- p.35 / Chapter CHAPTER 2 --- Hypotheses, Objectives and Study Design --- p.35 / Chapter 2.1 --- Hypothesis --- p.35 / Chapter 2.2 --- Objective --- p.36 / Chapter 2.3 --- Study design --- p.37 / Chapter CHAPTER 3 --- Bone Marrow-derived Mesenchymal Stem Cells Promote Growth and Angiogenesis of Breast and Prostate Tumors (Study I) --- p.40 / Chapter 3.1 --- Materials and Methods --- p.40 / Chapter 3.2 --- Results --- p.49 / Chapter 3.3 --- Discussion --- p.64 / Chapter 3.4 --- Conclusions --- p.67 / Chapter CHAPTER 4 --- Immortalized human fetal bone marrow-derived mesenchymal stem cell expressing anti-tumor suicide gene for anti-tumor therapy in vitro and in vivo (Study II) --- p.68 / Chapter 4.1 --- Materials and Methods --- p.68 / Chapter 4.2 --- Results --- p.73 / Chapter 4.3 --- Discussion --- p.85 / Chapter CHAPTER 5 --- Enhanced antitumor effects by combination therapy using mesenchymal stem cell expressing anti-tumor suicide gene and Doxorubicin in a xenograft mouse model (Study III) --- p.89 / Chapter 5.1 --- Materials and Methods --- p.89 / Chapter 5.2 --- Results --- p.97 / Chapter 5.3 --- Discussion --- p.111 / Chapter CHAPTER 6 --- General discussion and conclusions --- p.116 / Chapter 6.1 --- General discussion --- p.116 / Chapter 6.2 --- General conclusions --- p.119 / FUNDING --- p.120 / REFERENCE --- p.120

O presente trabalho teve como objetivo comparar a técnica de acesso cirúrgico preconizada por Boyne e Sands com a técnica de acesso cirúrgico preconizada por López-Cédrun por meio de avaliação da saúde periodontal na região da fissura alveolar após realização de enxerto ósseo alveolar. Dez indivíduos foram distribuídos em dois grupos correspondentes aos tipos de acesso cirúrgico propostos e submetidos ao enxerto ósseo alveolar com proteína óssea morfogenética recombinante humana (rhBMP-2): Grupo 1 - técnica de acesso proposta por Boyne e Sands - grupo controle (n=5); Grupo 2 - técnica de acesso proposta por López-Cedrún (n=5). Foram realizadas avaliações clínicas pré-operatórias (Baseline) e pós-operatórias (90 dias) de profundidade de sondagem e quantidade de mucosa queratinizada. Também foi realizado uma avaliação da condição estética de tecido mole (PES-Pink Esthetic Score) por meio de avaliação fotográfica. Os dados foram tabulados e submetidos a análise descritiva dos dados. Para a comparação da variação entre períodos (Baseline e 90 dias pós-operatório) das variáveis profundidade de sondagem e mucosa queratinizada, os dados foram submetidos ao teste t pareado. As técnicas cirúrgicas, e as variáveis profundidade de sondagem e mucosa queratinizado, foram comparados por meio de teste t independente. A análise da condição estética de tecido mole foi realizada pelo teste U de Mann-Whitney. A avaliação entre os períodos (Baseline e 90 dias PO) demonstrou que a técnica de Boyne e Sands proporcionou diminuição significativa da profundidade de sondagem do primeiro dente (P=0,047) e quantidade de mucosa queratinizada do terceiro dente do segmento distal à fissura (P=0,05). A técnica de López-Cedrún apresentou resultados semelhantes em relação a profundidade de sondagem e quantidade de mucosa queratinizada para todos os dentes avaliados (P>0,05). As técnicas cirúrgicas mostraram-se semelhantes em relação à profundidade de sondagem e mucosa queratinizada quando comparadas (P>0,05). Para o índice de Estética Rosa as técnicas de acesso apresentaram semelhança em relação a condição estética da papila mesial, papila distal, nível do tecido mole marginal, contorno do tecido mole, processo alveolar, cor e textura do tecido mole do primeiro, segundo e terceiro dente no segmento distal (P>0,05). A técnica de López-Cedrún proporcionou maior condição estética global de tecido mole para o segundo e terceiro dente (P<0,05). Pode-se concluir que as técnicas de Boyne e Sands e López-Cedrún apresentam resultados semelhantes em relação a saúde periodontal. A técnica de López-Cedrún proporcionou maior condição estética global de tecido mole / This study aimed to compare the surgical access technique developed by Boyne and Sands with the surgical access technique developed by López-Cédrun by evaluating the periodontal health in the alveolar cleft region after performing secondary alveolar bone graft. Ten subjects were divided into two groups corresponding to the types of surgical access proposed and submitted to alveolar bone graft with recombinant human bone morphogenetic protein (rhBMP-2): Group 1 - surgical technique proposed by Boyne and Sands - control group (n = 5); Group 2 - surgical technique proposed by López-Cedrún (n = 5). clinical evaluations of the preoperative (baseline) and postoperative (90 days) Were performed by probing pocket depth and measuring the amount of keratinized tissue. It was also performed an evaluation of the aesthetic condition of soft tissue (PES-Pink Esthetic Score) by means of photographic evaluation. Data were tabulated and submitted to descriptive analysis. For comparing the variation between periods (baseline and 90 days postoperative) of the variables probing pocket depth and keratinized tissue amount, the data were submitted to paired t test. The surgical techniques, the probing pocket depth and keratinized tissue amount variables were compared using independent t test. The analysis of soft tissue aesthetic condition was performed by the Mann-Whitney U test. By comparing periods (baseline and 90 days postoperative), Boyne and Sands technique provided a significant reduction of the first tooth probing pocket depth (P =.047) and keratinized tissue amount of the third tooth distal fissure segment (P =.05). The López-Cedrun technique resulted in similar probing pocket depth and keratinized tissue amount results for all evaluated teeth (P>.05) in periods comparison. Surgical techniques were similar in relation to probing pocket depth and keratinized tissue amount compared (P>.05). For Pink Esthetic Score surgical techniques were similar in relation of the aesthetic condition of mesial papilla, distal papilla, marginal level soft tissue, soft tissue contour, alveolar process, color and texture of the soft tissue of the first, second and third tooth distal segment (P>.05). López-Cedrún technique provided better overall aesthetic soft tissue condition for the second and third tooth (P<.05). It can be concluded that Boyne and Sands and López-Cedrún techniques have similar results for periodontal health. López-Cedrún technique provided greater overall aesthetic condition of soft tissue

INTRODUÇÃO: A cistatina C é uma proteína não glicosilada de baixo peso molecular que é produzida por todas as células nucleadas. A medida da concentração sérica (CS) de cistatina C tem sido aclamada como um marcador de função renal superior à medida da CS de creatinina. No presente estudo, avaliou-se a acurácia diagnóstica da proteína cistatina C em estimar mudanças no Ritmo de Filtração Glomerular (RFG) medido por 51Cr-EDTA, em análise longitudinal prospectiva de pacientes transplantados renais com tempo de transplante recente e tardio. Em uma fase inicial (Fase A), definimos a melhor estratégia metodológica para a realização do RFG por depuração plasmática de 51Cr-EDTA em receptores de enxerto renal utilizando a depuração renal de inulina como método padrão-ouro. MÉTODOS: Medidas simultâneas de depuração renal de inulina e de depuração plasmática de 51Cr-EDTA foram feitas em pacientes transplantados renais. A precisão do método de medida do RFG por 51Cr-EDTA foi avaliada em doadores após um ano de doação de rim. A análise de Bland&Altman foi empregada para avaliar a concordância entre os métodos. Em uma segunda fase, foram realizadas medidas das CS de cistatina C e de creatinina e do RFG por 51Cr-EDTA nos meses 1, 3, 6 e 12 de seguimento clínico do estudo em pacientes transplantados renais. A cistatina C foi dosada em amostras de soro, por técnica de imunonefelometria (N Latex Cystatin C kit - Dade Behring). A tendência da função renal foi obtida por Regressão Linear Simples. RESULTADOS: Na fase A, foram incluídos 44 pacientes transplantados renais e 22 doadores de rim com tempo de doação de 12,4 a 53,5 meses. A depuração de 51Cr-EDTA com amostras de sangue coletadas nos tempos 2, 4, 6 e 8 horas após injeção do radiofármaco apresentou forte correlação e alto grau de concordância com a depuração de inulina; uma estratégia única para todos os níveis de função foi estabelecida com amostras de sangue nos tempos 4 e 6 horas. Em uma segunda fase do estudo, oitenta e dois pacientes foram incluídos, com idade média de 43,4 ± 11,9 anos. A maioria era da raça branca (56%) e do sexo masculino (68%). No mês 1, a média do RFG por 51Cr-EDTA foi de 50,6 ± 17,3 ml/min/1,73m², e foi de 1,62 ± 0,65 mg/L para a CS de cistatina C e de 1,40 ± 0,62 mg/dL para a CS de creatinina. Na análise transversal, foi encontrada uma forte correlação entre o RFG e a medida de CS de cistatina C. Entretanto, na análise longitudinal do seguimento clínico a CS de cistatina C não estimou a tendência de mudança no RFG. CONCLUSÕES: A depuração plasmática de 51Cr-EDTA é uma medida precisa e acurada de RFG que pode ser utilizada em substituição à depuração renal de inulina, em pacientes transplantados renais. Medidas seriadas da CS de cistatina C não foram capazes de detectar mudanças no RFG em pacientes transplantados renais. / INTRODUCTION: Cystatin C is a nonglycosylated protein that is synthesized by all nucleated cells. The present study aimed to analyze the accuracy of serum concentration of cystatin C for detecting longitudinal change in glomerular filtration rate in transplanted recipients, as well to define a better methodological strategy to perform the plasma clearance of 51Cr-EDTA in renal transplant patients using inulin clearance as the gold standard method. METHODS: in the first phase of the study, simultaneous measurements of plasma clearance of 51Cr-EDTA and renal clearance of inulin in stable renal transplanted patients were performed. The within-subject repeatability of the 51Cr-EDTA was evaluated in live kidney donors at least 12 months after donation. Bland&Altman statistical approach was used to quantify the degree of agreement between clearance of inulin and plasma clearance of 51Cr-EDTA. In a second phase, serial measures of plasma clearance of 51Cr-EDTA, serum cystatin C and serum creatinine were examined in folowing at 1, 3, 6 and 12 months in kidney transplanted patients. Serum cystatin C was measured by a nephelometric immunoassay (N latex cystatin C kit - Dade Behring). The trend in renal function over time was obtained by linear regression. RESULTS: In the first phase, 44 transplanted patients and 22 kidney donors at least 12 months after donation (range 12,4 to 53,5 months) were enrolled. Plasma clearance of 51Cr-EDTA with four samples taken at 2, 4, 6 and 8 hours presented a strong association and closely agreement with inulin clearance. An abbreviated strategy was recommended with two blood sampling collected at 4 and 6 hours. In the second phase, 82 kidney transplanted patients were enrolled. Mean age was 43.4 ± 11.9 years. The majority were white (56%) and male (68%). The mean of the plasma clearance of 51Cr-EDTA was 50.6 ± 17.3, and it was 1.62 ± 0.65 mg/L and 1.40 ± 0.62 mg/dL for serum cystatin C and creatinine, respectively, at baseline. In cross-section analysis, serum cystatin C was strongly correlated with plasma clearance of 51Cr-EDTA. However, in longitudinal analysis serum cystatin C was not able for estimate GFR. CONCLUSIONS: Plasma clearance of 51Cr-EDTA is a precise method to measure GFR in renal transplanted recipients. The results showed that serial measurements of serum cystatin C are not able to detect trends in renal function in transplanted patients.

O estudo anatômico dos ossos dos maxilares é de extremo interesse devido à elevada demanda por procedimentos cirúrgicos como implantes osseointegrados e cirurgias ortognáticas. Embora uma variedade de substitutos ósseos seja utilizada para restabelecer a quantidade necessária de osso para instalação de implantes, existe um particular interesse em relação aos enxertos ósseos autógenos, que se mostram superiores, principalmente pela previsibilidade e altas taxas de sucesso. O objetivo desse trabalho foi quantificar o volume ósseo disponível na região posterior de mandíbula através da Tomografia Computadorizada de Feixe Cônico. A TCFC permite realizar medições com precisão e é uma ferramenta útil para avaliação préoperatória em cirurgia odontológica, já que o campo de imagem relativamente pequeno limita a exposição do paciente à radiação. Foram analisados 1.500 exames de TCFC e selecionados 70 exames do arquivo de imagens do Departamento de Estomatologia da Faculdade de Odontologia de Bauru, avaliados bilateralmente nas reformatações panorâmica e parassagitais através do software i-Cat Vision®. Na literatura não há consenso entre parâmetros e limites de osso. Dessa forma, foram definidas algumas referências: a distal da coroa do primeiro molar inferior como o limite anterior do enxerto e o local onde a cúspide mais alta dos molares cruza a borda anterior do ramo ascendente da mandíbula como o limite posterior do enxerto. Nessa região avaliou-se comprimento, altura, espessura de osso e volume da cortical óssea vestibular para enxertia óssea. Os resultados mostraram um volume médio de 859,26 mm3, sendo que a espessura média do osso cortical foi de 2,60mm, o comprimento médio foi de 18,98mm e a média de altura de 17,33mm. Esses valores mostram que a região posterior da mandíbula pode ser utilizada com segurança como área doadora de osso autógeno para reconstrução de pequenos defeitos e, usando esta estimativa de disponibilidade óssea, o cirurgião estará mais seguro para enfrentar os desafios da reconstrução maxilofacial. / The anatomical study of the bones of the jaw is of extreme interest due to the high demand for surgical procedures such as dental implants and orthognathic surgery. Although a variety of bone substitutes are used for restoring the necessary amount of bone for implant placement, there is a particular interest in relation to autogenous bone grafts, which are superior primarily by the predictability and high success rates. The aim of the present study was to quantify the bone volume available on the posterior region of the mandible through Cone Beam Computed Tomography. CBCT allows for an accurate measurement and is a useful tool for preoperative evaluations in dental surgery, since the relatively small image field limits the patient\'s exposure to radiation. Thousand five hundred CBCT exams were analyzed and selected seventy exams of the archives of images from the Department of Stomatology, Bauru School of Dentistry, bilaterally assessed in panoramic and parasagittal reformatting through the i-Cat Vision® software. In the literature there is no consensus between parameters and bone limits. Thus, we determined some references: the distal of the first mandibular molar crown as the anterior limit of the graft, and where the highest cuspid of mandibular molars crosses the anterior border of the ascending ramus of the mandible as the posterior limit of the graft. In this region were evaluated length, height, bone thickness and volume of the vestibular cortical bone for bone grafting. The results showed an average volume of 859.26mm3, while the average thickness of cortical bone was 2.60mm, an average length of 18.98mm and an average height of 17.33mm. These values show that the posterior mandible can be safely used as donor area of autologous bone to rebuild small areas, and using this estimate of available bone, the surgeon will be safer to face the challenges of maxillofacial reconstruction.

Objetivo: Avaliar a função visual de pacientes submetidos a transplante lamelar anterior profundo (DALK) utilizando a dissecção com tunelizador manual e fio. Métodos: Foram incluídos 33 pacientes com ceratocone que apresentavam BCVA <= 0,60 LogMar, miopia e astigmatismo entre 8,00 e 10,00D, K central médio > 53,00D, ausência de cicatrizes, espessura corneana mínima entre 300 e 400 um. Foi feita avaliação oftalmológica completa no pré e no pós-operatório de 6 a 8 meses. Estas avaliações foram complementadas com exame topográfico da córnea, microscopia especular para avaliação da densidade das células endoteliais corneanas, aberrometria corneana e exame de tomografia de coerência óptica do segmento anterior. As variáveis BCVA, UCBA e os valores totais das aberrações corneanas de alta ordem foram correlacionadas com a espessura do leito estromal residual. Resultados: Os pacientes submetidos à DALK apresentaram BCVA de 0,68 ± 0,27 LogMar o que representa BCVA superior a 20/40 em 60% da amostra analisada. Não foram observadas micro ou macroperfurações. Houve diminuição na contagem endotelial de 2702,87 ± 548,87 células por mm2 para 2282,10 ± 525,66 células por mm2 . A dissecção do estroma profundo com o fio facilitou a remoção de tecido estromal posterior, fato corroborado com o achado de que o leito residual estromal aferido foi de 49,18 ± 18,36 ?m na região central e foi inferior a 80 ?m em grande parte dos pacientes estudados. No que se refere à regularidade da dissecção, observou-se tendência a valores mais elevados de espessura residual na periferia (60,09 ± 17,70 ?m). Não houve correlação da BCVA, UCVA e do total de aberrações de alta ordem da córnea com a espessura do leito estromal residual. Conclusão: A apreciação dos resultados desse estudo mostrou que com a técnica utilizada para realização de DALK em portadores de ceratocone obteve-se resultados topográficos e funcionais semelhantes a outras técnicas consagradas pela literatura. A facilidade na dissecção do estroma profundo, a regularidade da dissecção e a presença de baixíssimo índice de conversão para transplantes penetrantes são encorajadores / Objective: Evaluate the visual function of patients undergoing deep anterior lamellar keratoplasty (DALK) using a manual spatula and a wire dissection. Methods: Thirty three keratoconus patients were included, meeting the following inclusion criteria: BCVA logMAR <=0,60, myopia and astigmatism between 8.00 and 10,00D, K central average > 53.00D, no corneal scars and minimal corneal thickness between 300 and 400 um. Complete ocular evaluation was performed preoperatively and postoperatively in 6-8 months. These assessments were supplemented by topographical survey of the cornea, specular microscopy to evaluate the density of corneal endothelial cells, corneal wavefront analysis and examination of optical coherence tomography of the anterior segment (Visante). The BCVA variables, UCVA and the total amounts of corneal higher-order aberrations were correlated with the the residual stromal bed thickness. Results: Patients that undergone to DALK with the described technique presented a BCVA of 0.68 ± 0.27 logMAR which represents a BCVA of more than 20/40 at 60% of the analyzed sample. There were no micro or macroperforations. We observed a small decrease in the endothelial cell count from 2702.87 ± 548.87 cells per mm2 to 2282.10 ± 525.66 cells per mm2. The dissection of the deep stroma with a wire facilitated the posterior stromal tissue removal, thus the measured stromal bed thickness was 49.18 ± 18.36 ?m in the central region and less than 80 ?m in the majority of the studied patients. As regards the dissection regularity, we showed a tendency to higher values of residual thickness at the periphery (60.09 ± 17.70 ?m). There was no correlation of the BCVA, UCVA and total corneal higher-order aberrations with the residual stromal bed thickness. Conclusion: The assessment of the study data showed that the described technique achieved a topographical and functional result similar to other techniques consecrated by literature. The shallow learning curve, the ease to perform the dissection of the deep stroma, the postoperative stromal regularity and the presence of very low conversion rate for penetrating keratoplasty are encouraging

O transplante de fígado é considerado o tratamento de eleição para o paciente com doença hepática progressiva, irreversível e terminal, o qual não encontra outro tipo de tratamento. O ensino é uma importante estratégia para o preparo dos candidatos ao transplante de fígado e constitui-se como papel relevante do enfermeiro. Para a condução da presente investigação adotou-se os pressupostos de Gagné e Ohler. O objetivo geral delimitado foi analisar o conhecimento de candidatos ao transplante de fígado, antes e depois da implementação de uma intervenção educativa. A investigação foi conduzida em duas fases. Na primeira fase realizou-se um estudo descritivo para identificar as características sócio-demográficas, clínicas e as necessidades de informação dos candidatos. Na segunda fase procedeu-se um estudo piloto, para analisar o conhecimento dos candidatos antes e depois da aplicação da intervenção educativa, e avaliar a satisfação destes com as informações recebidas. Frente a uma casuística de 55 candidatos na primeira fase, observou-se uma predominância do sexo masculino, com idade média de 50,25 anos, média de 8,49 anos de estudo, 70,91% dos sujeitos estavam afastados de atividades laborais e a renda predominante foi de dois a seis salários mínimos. A maioria dos candidatos era CHILD B, com MELD médio de 14,91 pontos, 72,72% estavam acima do peso e apresentavam uma evolução da doença crônica do fígado de 101,21 meses em média. A maioria da amostra apresentava cirrose causada por vírus e alcoolismo. O tempo médio de fila de espera foi de 1199,58 dias. Dentre as principais manifestações clínicas, destacou-se a presença de ascite (58,18%), varizes esofágicas (81,82%), encefalopatia hepática (50,91%) e hemorragia digestiva prévia (47,27%). As necessidades de informação relacionadas com o período pré-operatório foram as que obtiveram as pontuações médias maiores. As complicações após o transplante e os cuidados necessários após o transplante também foram necessidades de informação indicadas como relevantes pelos candidatos. Diante de uma amostra de 15 pacientes para a segunda fase do estudo, observou-se um ganho cognitivo significativo após a intervenção, com uma melhora de quase 20% no desempenho dos candidatos (p<0,05). Em relação à satisfação dos candidatos, observou-se uma avaliação positiva da satisfação com as informações recebidas. As informações que geraram índices maiores de satisfação foram relacionadas ao período pós-operatório e os cuidados necessários por toda a vida. A relação entre o conhecimento após a intervenção e o grau de satisfação mostrou uma correlação significativa (p<0,05). O estudo fornece evidências de que a provisão de informações de qualidade é capaz de aumentar o conhecimento e proporcionar satisfação para os candidatos ao transplante de fígado. / Liver transplant is considered the preferred treatment for patients with progressive, irreversible and terminal liver disease, who cannot find any other treatment type. Teaching is an important strategy to prepare liver transplant candidates and represents a relevant role for nurses. This research is based on Gagné and Ohlers premises. The general aim was to analyze liver transplant candidates knowledge before and after an educative intervention. The research was conducted in two phases. First, a descriptive study was carried out to identify the candidates sociodemographic and clinical characteristics and information needs. In the second phase, a pilot study was performed to analyze the candidates knowledge before and after the educative intervention, as well as to assess their satisfaction with the information they received. The sample comprised 55 candidates: a majority were men; the average age was 50.25 years and average education 8.49 years; 70.91% of subjects were on leave from their job and the predominant income was between two and six minimum wages. Most candidates were CHILD B, the mean MELD score was 14.91 points, 72.72% were overweight and the average evolution of the chronic liver diseases was 101.21 months. Most patients in the sample presented cirrhosis caused by virus and alcoholism. The mean waiting time for a transplant was 1199.58 days. The main clinical manifestations included ascites (58.18%), esophageal varices (81.82%), hepatic encephalopathy (50.91%) and previous digestive hemorrhage (47.27%). Information needs related to the preoperative period obtained the highest mean scores. Candidates also indicated information needs related to post-transplant complications and necessary care. In a sample of 15 patients for the second phase, significant cognitive gain was observed after the intervention, with an almost 20% improvement in candidates performance (p<0,05). Candidates satisfaction with the information they received was assessed positively. Higher satisfaction levels were found for information related to the postoperative period and care needed across the lifetime. Significant correlation was found (p<0.05) between knowledge after the intervention and satisfaction level. This research evidences that providing quality information can increase liver transplant candidates knowledge and give them satisfaction.

In conclusion, the present study firstly addressed the relationship between graft incorporation and peri-graft bone quality and quantity after ACL reconstruction in a rabbit model. The findings suggested that the non-invasive measurement of peri-graft bone would be useful to predict graft incorporation. Peri-graft bone loss was region-specific after surgery, which might be associated with stress shielding in the specific region after tunnel creation. The use of Brushite CPC might be a promising way to augment peri-graft bone and enhance graft incorporation. (Abstract shortened by UMI.) / In the fourth part, brushite CPC was successfully applied to augment the peri-tendon bone volume and connectivity. It was revealed under mechanical testing that the ultimate strength and stiffness of graft fixation in bone tunnel on experimental side was higher than that of the control by 117% and 102% respectively at 6 weeks, postoperatively (p&lt;0.05 for both). The use of brushite CPC caused a paradigm shift in failure mode from intra-tunnel to intra-articular portion at 12 weeks postoperatively (p=0.013). / Keywords. anterior cruciate ligament reconstruction, bone mass, microarchitecture, tendon-to-bone healing, graft incorporation, brushite calcium phosphate cement / The first part of this thesis compared the histological characteristics of T-B healing interface tissue in femoral and tibial tunnels following ACL reconstruction in rabbits. Results revealed that less cartilaginous interface tissue was formed in tibial tunnel than in femoral tunnel. Such cartilaginous tissue was gradually mineralized during reestablishment of a direct T-B integration. T-B healing in tibial tunnel was inferior to that in femoral tunnel. The disparity of T-B healing in various osseous milieus suggested the potential association in between. / The second part of this original work further explored the numeric relationship between the strength of T-B attachment and peri-graft bone mass and connectivity. Results of Micro-computed tomography (micro-CT) showed that peri-graft bone mass and connectivity was significantly lower on tibial side than those on femoral side. It was found under biomechanical evaluation that grafted tendon was prone to be pulled out from tibial tunnel with the bone attachment; the weakest point of the complexes shifted from the healing interface at time zero to peri-graft bone at week 6 after operation. With reverse of peri-graft bone at week 12 postoperatively, the weakest point shifted to intra-osseous tendinous portion. The stiffness of graft fixation correlated with peri-graft BV/TV (r2=0.68, p=0.001) and connectivity (r2=0.47, p=0.013) at week 6 after operation. / The third part addressed the changes of peri-graft bone in spatial and temporal manners using high resoluation multiple-slice peripheral quantitative computed tomography (pQCT) and micro-CT. Under pQCT evaluation, a decrease in BMD was present in specific regions, medial region of femoral tunnel by 26% and posterior and lateral regions of tibial tunnel by 22% and 42%, respectively at week 12 postoperatively than the baseline (p&lt;0.05 for all). It was accompanied by a decrease in trabecular number and increase in trabecular spacing, the shift of plate-like to rod-like trabeculae and loss of anisotropy under micro-CT evaluation. It was echoed by histological findings showing increased osteoclastic activities and poor T-B healing in these specific regions. The postoperative bone loss and associated poor T-B healing was region-specific. / by Wen, Chunyi. / Adviser: Kai-ming Chan. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0217. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 148-168). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

Aims There are few proven therapies that can protect against the inevitable ischaemia reperfusion injury (IRI) that occurs during renal transplantation. IRI increases the likelihood of delayed graft function (DGF), which negatively impacts on the long-term survival of a transplanted kidney. One enzyme of interest, heme oxygenase-1 (HO-1), degrades heme and protects against the oxidative stress that occurs secondary to IRI. Clinical renal recipients with higher HO-1 levels have improved graft function post transplant. Heme arginate (HA), a form of hemin, which has been used to treat porphyria for over 30 years, has repeatedly been shown to induce HO-1 in in vivo and in vitro macrophages. It is one of the few HO-1 inducers approved for clinical use and healthy volunteer studies confirmed that HA could also safely induce HO-1 in humans. Prior to the formal start of the MD, the University of Edinburgh successfully applied to NHS Blood and Transplant for funding to investigate whether giving HA to recipients of deceased donor renal grafts prior to transplant could upregulate HO-1 and whether this had any effect on the function and health of the grafts. This MD aims to explain the background behind the proposed study, the process of study approval, planning and trial logistics and protocol. This thesis then describes the methods of sample analysis, the results and future directions for the HOT (Heme Oxygenase-1 in renal Transplantation) study. Methods The HOT study planning and approval process took eight months and the first participant was randomised in January 2012. The study was sponsored by ACCORD, a joint company from University of Edinburgh and NHS Lothian, and recruited patients from the Edinburgh Royal Infirmary Transplant Unit. The protocol was followed to ensure that 40 recipients were randomised blind to either active (two doses 3mg kg-1 HA: pre-operatively, day 2) or placebo (NaCl: same schedule). To ensure that the primary outcome was fulfilled, recipient blood was taken daily for peripheral blood mononuclear cells (PBMC) extraction. After further blinding steps, the PBMCs were analysed for HO-1 protein and mRNA. The secondary outcome measures involved collecting urine for analysis of urinary biomarkers (KIM-1 and NGAL), taking renal graft biopsies pre-op and day 5 for renal HO-1 analysis and collecting renal function data. DGF was calculated daily. To ensure that all adverse event data was captured, the recipients were closely reviewed for 7 days and their renal function was monitored for 90 days. Results The final participant was recruited in May 2013 within the predicted timescale and to budget. This participant completed follow-up in August 2013. Of the 40 participants, three received the infusion but did not receive a transplant and therefore could not give primary outcome data. The remaining 37 did and this was analysed. Adverse events were equivalent between groups and there were no adverse reactions to HA. HA upregulated PBMC HO-1 protein at 24 hours compared to placebo: HA 11.1ng/ml (1.0- 37.0) vs. placebo 0.14ng/ml (-0.7- 0.3)(p= < 0.0001). PBMC HO-1 mRNA was also increased: HA 2.73 fold (1.8- 3.2) vs. placebo 1.41 fold (1.2- 2.2) (p=0.02). HA increased HO-1 protein immunopositivity in day 5 renal tissue compared with placebo: HA 0.21 (-24- 0.7) vs. placebo -0.03 (-76- 0.15) (p=0.02) and the percentage of HO-1 positive renal macrophages also increased: HA 50.8 cells per HPF (40.0- 59.8) vs. placebo 22.3 (0- 34.8) (p=0.012). Renal HO-1 mRNA was also increased in HA group: 2.02 (0.20- 4.03) fold increase compared to 1.68 (0.75- 10.39) fold in the placebo group but it was not significant (p= 0.451). Urinary biomarkers were reduced after HA but not significantly so. Histological injury and DGF rates were similar between the groups. Conclusion HA is safe and effective in renal transplant recipients as reported in this phase II, randomised, placebo controlled, blinded, single-centre study. The primary outcome was achieved and demonstrated for the first time that HA induces HO-1 in peripheral and renal macrophages in kidney transplant recipients. There was also evidence that HA increased HO-1 expression in renal tissue. There was no evidence that HA improved renal function or reduced injury as seen in animal models but it is recognised that the sample size was small and the study was not powered to these endpoints. Larger studies are planned to determine the impact of HO-1 upregulation on clinical outcomes and evaluate the benefit to patients at risk of IRI. The plans for HOT2 are expanded in this thesis.

A Leucemia Mielóide Crônica (LMC) é uma doença rara. No entanto, os avanços nas pesquisas básica e clínica nos últimos anos, colocaram a LMC em evidência sendo hoje uma neoplasia maligna potencialmente curável. O diagnóstico e tratamento desta doença são, no entanto, extremamente caros. Não havendo dados sistemáticos nem registros de incidência da LMC no Rio Grande do Sul ou no Brasil, o levantamento de dados baseado em registros dos centros de referência se justifica também para planejar ações em saúde. Entre 1996 e 2000, 276 casos foram diagnosticados. A estimativa de casos novos anuais foi de aproximadamente 0,6:100.000 habitantes, e a idade média no momento do diagnóstico foi 42 anos e 4 meses (±16 anos e 2 meses). Quanto ao tratamento e evolução destes pacientes, dos 257 avaliados, 56 (21,8%) foram submetidos ao transplante alogênico de medula óssea, com taxa de sobrevida em 5 anos de 75% e 27% para as fases crônica e acelerada/blástica, respectivamente. O tempo médio de sobrevida para os 257 pacientes foi de 47,7 meses (IC 43,3 - 52,1). Comparando ao relatado na literatura, encontramos um menor número anual de novos casos e também uma média de idade no diagnóstico mais baixa. Isto poderia ser explicado pela menor referência de idosos a serviços terciários de saúde. Para os pacientes transplantados, os resultados foram semelhantes aos relatados na literatura. / Although rare, the advances made in basic and clinical research throughout the last years have thrown a spotlight on CML. Diagnosis and treatment of CML is of high cost. Since there is no systematic data or information about the incidence of CML in Rio Grande do Sul or Brazil, the data obtained from reference centers serve to estimate the number of CML cases in our state to better plan health actions. Between 1996 and 2000, 276 cases were diagnosed. The annual estimate of new cases was approximately of 0,6:100,000 inhabitants, and the median age at diagnosis was 42 years and 4 months (±16 years and 2 months). The mean overall survival time for the 257 patients was 47,7 months (CI 43,3-52,1). That could be explained by the lack of referral for older patients. Regarding treatment and evolution, of the 257 valuable patients, 56 (21,8%) were submitted to allogeneic BMT with a five-year survival of 75% and 27% for chronic and accelerated/blastic phases, respectively. In conclusion, we found a lower estimated incidence and a lower median age at diagnosis. For the transplanted patients the results were similar to those reported in the literature.