Introdução: O transplante renal (TR) é o tratamento de escolha para uma significativa porção de pacientes com perda crônica terminal da função renal. Apesar dos progressos obtidos, a disfunção inicial do enxerto (DIE) permanece como uma importante complicação precoce muitas vezes levando à necessidade da biópsia renal. Essa, apesar de suas limitações, riscos e custos, é considerada padrão ouro para a avaliação das disfunções dos enxertos renais. Assim sendo é imprescindível estudar e buscar biomarcadores não invasivos capazes de diagnosticar as agressões aos transplantes renais, em especial na fase de DIE, quando os parâmetros funcionais não estão disponíveis. Objetivo: Analisar e quantificar a expressão do micro Ácido Ribonucleico (miRNA) mi RNA-146a-5p em amostras de sangue periférico e tecido renal de pacientes que desenvolveram disfunção do enxerto associados a lesões de isquemia e reperfusão após transplante renal. Métodos: Trata-se de um estudo transversal. Os pacientes submetidos a transplante renal que necessitarem de biópsia devido à presença de DIE foram convidados a participar da pesquisa e a assinarem o Termo de Consentimento Livre e Esclarecido. As amostras foram armazenadas no período de março de 2013 a abril de 2017. Posteriormente foi avaliada a expressão do micro RNA (miR-146 a-5p) em tecido renal e em sangue periférico. Resultados: Em amostras de biópsia renal, encontramos um aumento estatisticamente significativo na expressão de miR-146a-5p no grupo de disfunção inicial do enxerto (DIE, n=33) versus grupo de pacientes estáveis (STA, n=13), P= 0,019 no grupo de pacientes com rejeição aguda (RA, n=9) versus grupo de DIE não observamos diferença significativa, P=0,106, assim como o grupo de pacientes estáveis versus RA não observamos diferença significativa, P= 1,000. Diferença na análise global P = 0,008. No entanto, em amostras de sangue periférico encontramos aumento na expressão gênica de miR-146a-5p no grupo de DIE versus pacientes STA , porém, não foi estatisticamente significativo, P= 0,083. Não houve correlação entre a expressão miR-146a-5p nos diferentes grupos de biópsia e sangue periférico, P=0,541. Conclusão: A expressão do miR 146a-5p apresentou expressão gênica distinta na disfunção inicial do enxerto em amostras de biópsias, podendo vir a ser considerado potencial biomarcador de lesão de isquemia e reperfusão renal. / Introduction: Kidney transplantation is the treatment of choice for a significant portion of patients with chronic terminal loss of renal function. Despite the progress achieved, delayed graft function DGF remains an important early complication. Graft biopsy, despite its limitations, risks and costs, is considered a gold standard for the diagnosis of graft dysfunction. Therefore, it is imperative to study and search for noninvasive biomarkers capable of diagnosing injuries to kidney transplants, especially in the DGF period when functional parameters are not available. The objective of the present study was to analyze and quantify the expression of miRNA-146a -5p ribonucleic micro-acids (miRNAs) in peripheral blood and renal tissue samples obtained from patients who underwent renal transplantation and developed DGF which is associated with lesions of ischemia and reperfusion injuries, after renal transplantation. Methods: This is controlled cross-sectional study involving transplant recipients, between March 2013 and April 2017, that underwent DGF and received a graft biopsy. Patients had their tissue and peripheral blood samples stored and latter analyzed for the expression of the micro-RNA: miR-146a-5p in renal tissue and blood. (Continuatiation) Results: In graft tissue samples a statistically significant increase in miR-146a-5p expression in the initial graft dysfunction group (DIE, n=33) was observed in the comparison with the group of stable patients (STA, n=13) group, P=0,019. The difference wasn’t significant in the comparison with the acute rejection (AR, n=9) group versus group DIE, P=0,106, as well stable patients group versus AR we didn’t observe a significant difference, P=1,000 . Overall group significance P=0.008. However, in peripheral blood samples we found an increase in miR-146a-5p gene expression in the DIE group versus STA patients, however, it was not statistically significant, P = 0.083. There was no correlation between expression miR-146a-5p in the renal tissue and peripheral blood samples, P=0,541. Conclusion: We concluded that miR-146a-5p expression has a distinct pattern of expression in the setting of DGF and has the potential of becoming a biomarker for ischemia and reperfusion injury in kidney transplant recipients.

Objetivo: comparar a profilaxia universal com a terapia preemptiva com ganciclovir endovenoso no manejo da citomegalovirose em pacientes transplantados de pulmão em uma coorte retrospectiva. Metodologia: de março de 1999 a dezembro de 2009 foram estudados, no Serviço de Transplante do Complexo Hospitalar Santa Casa de Porto Alegre, todos os pacientes submetidos a transplante pulmonar, procurando-se verificar a ocorrência de citomegalovirose relacionada ao tipo de tratamento profilático anti-viral utilizado (universal e preemptiva). Foram excluídos, em ambos os grupos, os pacientes nos quais não tivesse sido registrada a antigenemia no primeiro mês após o transplante, e os que foram a óbito dentro dos primeiros trinta dias após a cirurgia. Resultados: de 224 pacientes transplantados no período referido, 66 (29,5%) foram excluídos por óbito precoce. Os 158 pacientes que entraram no estudo tinham idade de 51±15 anos (7 anoa-71 anos), e 61,0% eram do sexo masculino; 150 (95%) receberam o órgão de doador cadavérico, e 134 (85,0%) foram submetidos a transplante unilateral. A profilaxia universal para citomegalovirus (CMV) foi realizada em 70 pacientes (44,0%) e a terapia preemptiva em 88 (56,0%). O grupo que recebeu profilaxia universal levou maior tempo para positivar o exame (p<0.001) comparado com o grupo que não a recebeu. Houve associação significativa entre profilaxia e antigenemia positiva no primeiro ano após o transplante (p=0.024). A mortalidade no primeiro e no quinto ano foi respectivamente de 20% e 50%. A sobrevida mediana do grupo com profilaxia universal foi 3.8 anos (IC95% de 2.5 a 5.0) e o grupo com terapia preemptiva de 4,3 anos (IC95% de 2.5 a 6.0), não apresentando diferença significativa. Conclusão: com base nos dados obtidos neste estudo a profilaxia universal e a terapia preemptiva demonstraram-se seguras e efetivas, entretanto os achados desta pesquisa não se demonstraram conclusivos para definir a melhor opção terapêutica. / Objective: To compare the universal prophylaxis and preemptive therapy for the treatment of cytomegalovirus in lung transplant patients in a retrospective cohort. Method: Performed at the Lung Transplant service in Santa Casa de Porto Alegre during the period from March 1999 to December 2009, upon reviewing the records and results of cytomegalovirus detection. Were excluded in both groups the patients who were not registered antigenemia in the first month after lung transplantation, due to death during this period. Results: 224 patients transplanted during the study period, 66 patients were excluded due to death within 30 days after transplantation. Mean age of patients was 51 ± 15 years old, 61.0% were men, 95.0% received organ of cadaveric donors, 85.0% were submited to unilateral transplant. The universal prophylaxis was performed in 44.0% of patients and preemptive therapy in 56.0%. The group receiving prophylaxis universal took longer to make positive antigenemia (p <0.001) when compared with the group not receiving prophylaxis. It was observed significant association between positive antigenemia and prophylaxis in the first year after transplantation (p = 0.024). The general mortality in the first and fifth year was 20.0% and 50.0% respectively. Survival of patients with prophylaxis presented a median of 3.8 (95% CI 2,5 to 5.0) years and the group that received no prophylaxis had a survival of 4,3 years (95% CI 2.5 to 6.0). Conclusion: Based on the data obtained in this study universal prophylaxis and preemptive therapy demonstrated to be safe and effective, however the findings of this research did not prove conclusive to determine the best treatment.

Racional: O carcinoma hepatocelular é uma neoplasia maligna agressiva com elevada morbidade e mortalidade. Objetivo: Revisão da literatura sobre o diagnóstico e o manejo do carcinoma hepatocelular nos vários estágios da doença. Método: Revisão da literatura utilizando a base Medline/PubMed e literatura adicional. Resultados: O carcinoma hepatocelular é geralmente complicação da cirrose hepática. As hepatites virais crônicas B e C também são fatores de risco para o surgimento do carcinoma hepatocelular. Quando associado à cirrose hepática, o carcinoma hepatocelular geralmente surge a partir da evolução de um nódulo regenerativo hepatocitário que sofre degeneração maligna. O diagnóstico é efetuado através de tomografia computadorizada de abdome com contraste endovenoso (efeito wash in e wash out), e a ressonância magnética pode auxiliar nos casos que não possam ser definidos pela tomografia computadorizada. O único tratamento potencialmente curativo para o carcinoma hepatocelular é a ressecção do tumor, seja ela realizada através de hepatectomia parcial ou de transplante. Infelizmente, apenas cerca de 15% dos carcinomas hepatocelulares são passíveis de tratamento cirúrgico. Pacientes portadores de cirrose hepática estágio Child B e C não devem ser submetidos à ressecção hepática parcial. Para esses pacientes, as opções terapêuticas curativas restringem-se ao transplante de fígado, desde que selecionáveis para esse procedimento, o que na maioria dos países dá-se através dos Critérios de Milão (lesão única com até 5 cm de diâmetro ou até três lesões de até 3 cm de diâmetro). A sobrevida em 5 anos para pacientes transplantados para o carcinoma hepatocelular pode alcançar 70% Conclusão: Quando diagnosticado em seus estágios iniciais, o carcinoma hepatocelular é potencialmente curável. O conhecimento das estratégias de 17 diagnóstico e tratamento do carcinoma hepatocelular a fim propiciam sua identificação precoce e a indicação de tratamento apropriado. / Introduction: Hepatocellular carcinoma is an aggressive malignant tumor with high lethality. Aim: A literature review on diagnosis and management of hepatocellular carcinoma was performed. Methods: Literature review utilizing databases Medline/PubMed. Results: Hepatocellular carcinoma is a common complication of hepatic cirrhosis. Chronic viral hepatitis B and C also constitute as risk factors for development of hepatocellular carcinoma. In patients with cirrhosis, hepatocelular carcinoma usually develops from a malignant transformation of a dysplastic regenerative nodule. Diagnosis is confirmed through computed tomography scan with intravenous contrast (wash in and wash out effect), and magnetic resonance may be helpful in some instances. Curative treatment for hepatocellular carcinoma may be performed through partial liver resection or liver transplantation. Only 15% of all hepatocellular carcinomas are localized and amenable to operative treatment. Patients with Child C liver cirrhosis are not amenable to partial liver resections. The only curative treatment for hepatocellular carcinomas in patients with Child B or C cirrhosis is liver transplantation. In most countries, only patients with hepatocellular carcinoma under Milan Criteria (single tumor with up to 5 cm diameter or up to three nodules with a maximum diameter of 3 cm) are considered candidates for liver transplant. Five-year survival following liver transplantation for hepatocellular carcinoma may reach 70%. Conclusion: Hepatocellular carcinoma is a potentially curable neoplasm if discovered in its initial stages. Clinicians and surgeons should be familiar with strategies for early diagnosis and treatment of hepatocellular carcinoma as a way to decrease mortality associated with this malignant neoplasm.

Introdução: No contexto do transplante de órgãos, a adesão à imunossupressão é imprescindível para evitar episódios de rejeição celular, perda do enxerto e óbito do paciente. No transplante hepático infantil, as taxas de não adesão aos imunossupressores variam de 10 a 70,4%, são aparentemente mais frequentes em pacientes adolescentes e raramente estudada em crianças abaixo de 12 anos de idade. Objetivos: determinar a prevalência de não adesão ao tacrolimo em crianças (idade no transplante < 12 anos), acompanhadas no Programa de Transplante Hepático Infantil do Hospital de Clínicas de Porto Alegre, transplantados por no mínimo 1 ano, traçar o perfil dos pacientes classificados como sem adesão e identificar as possíveis repercussões desta sobre o enxerto. Material e métodos: Trata-se de uma coorte histórica de um único centro, onde os pacientes foram recrutados do banco de dados da Unidade de Gastroenterologia Pediátrica do Hospital de Clínicas de Porto Alegre. Foram revisados os registros médicos de todos os pacientes pediátricos que receberam um enxerto hepático. Critérios de inclusão: procedimento realizado entre os períodos de 1999-2011, por qualquer indicação, em uso de tacrolimo como imunossupressão de manutenção e com no mínimo cinco níveis séricos do imunossupressor em intervalos de aproximadamente três meses. Excluídos pacientes em uso de medicamentos que pudessem interferir no nível sérico do imunossupressor. Não adesão ao tacrolimo foi definida como valores de desvio-padrão do medicamento ≥ 2, considerando-se no mínimo cinco medidas consecutivas do nível sérico (índice de variabilidade do nível do tacrolimo). As características clínicas, sociais, e demográficas dos pacientes, idade e nível educacional maternos definiram a variável perfil do paciente. ALT > 60 IU / l (excluídas infecção e hepatotoxicidade), rejeição celular histologicamente comprovada, perda do enxerto e morte do paciente definiram repercussão da não adesão sobre o enxerto. Análise Estatística: foram utilizados os testes T de Student para as variáveis descritivas e o qui-quadrado para as variáveis categóricas. Valores de p < 0,05 foram considerados significativos. Resultados: Oitenta e seis pacientes menores de 12 anos foram submetidos ao transplante hepático nos períodos entre 1999 e 2011. Destes, sessenta e cinco preencheram os critérios de inclusão. Quinze foram excluídos, resultando em uma amostra final de cinquenta pacientes. Vinte e oito eram do sexo masculino (56%) sendo a média de idade de 4,0 ± 3,5 anos. A atresia biliar representou 62% das indicações de transplante, 87,7% eram lactentes e escolares. Não adesão medicamentosa foi observada em 22 (44%) dos pacientes e nas famílias com maior renda (p=0,045). Houve uma tendência da não adesão ser mais frequente nas famílias cujas mães tinham maior escolaridade (p=0,051). A média de idade materna foi de 31 anos e esta variável não esteve associada aos desfechos. ALT > 60 UI/l foi mais frequente nos pacientes sem adesão medicamentosa (p=0,035) e prontamente resolvida após ajuste da imunossupressão. A rejeição celular aguda foi semelhante entre os grupos (p=0,90). Óbito ou perda do enxerto não foram observados. Conclusão: Houve alta variabilidade do nível de tacrolimo na amostra estudada. Esta foi mais prevalente nas famílias com maior renda. Elevação transitória da ALT foi a principal repercussão dessa variabilidade sobre o enxerto. O índice de variabilidade do nível sérico de tacrolimo ≥2DP pode sugerir alguma falha da adesão medicamentosa. / Introduction: In the context of organ transplantation, the adherence to immunosuppression is important to avoid cell rejection episodes, graft loss and patient death. In pediatric liver transplantation, the rates of non-adherence to immunossupressors vary from 10 to 70,4%. This is more frequent in teenage patients and it is rarely studied in children younger than twelve years old. Objectives: Determining the prevalence of non-adherence to tacrolimus in children (age at transplant below 12 years) followed in the Pediatric Liver Transplantation Program of Clinical Hospital of Porto Alegre (HCPA) for at least 1 year in order to establish these patients’ profile and identify possible repercussions of non-adherence of the graft. Materials and methods: This is a matter of a single center historical cohort in which patients were recruited from the Pediatric Gastroenterology Unit at HCPA. We verified medical records of all pediatric patients who received a liver graft. Inclusion criteria are: procedure carried out from 1999 to 2011 under any recommendation, using tacrolimus as a maintenance immunosupressor, and with at least five serum levels of tacrolimus in approximately every three months. Patients in treatment with medication that could interfere in the suppressor's serum level were excluded. Non-adherence to tacrolimus was defined when the medication standard deviation was greater than or equal to 2, considering at least five consecutive measurements of serum level (variability rates of the tacrolimus level). Each patient profile was defined by their clinical, social and demographic characteristics, as well as their mother's age and educational level. Alanine transaminase (ALT) higher than 60 UI/l (infection and hepatotoxity were excluded), histologically proved cell rejection, graft loss and patient death defined the repercussions on non-graft adherence. Statistical Analysis: We used T tests for the descriptive variables and chi-squared for the categorical variables. Values of p lower than 0.05 were considered as significant. Findings: Eighty-six patients younger than 12 years old were subject to liver transplantation between 1999 and 2011. From these, sixty-five patients fulfilled the inclusion criteria. Fifteen patients were excluded, resulting in a sample of fifty patients. Twenty-eight were male (56%) and the average age was 4.0 ± 3.5 years. Biliary atresia represented 62% of the transplant indications. 87.7% were infants and students. Nonadherence to medication was observed in 22 (44%) patients and it more prevalent it families with greater income (p = 0.045). Non-adherence tended to be more frequent in families in which mothers had a better level of education (p = 0.051). The average age of the mothers was 31 years old and this variable was not associated with the outcomes. ALT> 60 IU/l was more frequent in patients without adherence to medication (p = 0.035) and immediately solved after an adjustment of the immunosuppression. Acute cell rejection was similar among groups (p = 0.90). Death and graft loss were not observed. Conclusion: There was a high variability in tacrolimus levels in the sample studied. This was more prevalent in families with higher income. Temporary elevation of ALT was the main effect of this variability on the graft. The variability rates of the serum level of tacrolimus, which was greater or equal to 2 SD (Standard deviation), may suggest failure of the medication adherence.

Organtransplantation är för vissa svårt sjuka individer den enda möjliga behandlingen till ett fortsatt liv. För dessa individer är väntan på organtransplantation av lever, hjärta eller lunga ofta en oviss väntan på en livsviktig operation. Denna väntan innebär en förändring och begränsning i individens vardag och påverkar inte bara individen själv utan även närstående. Detta är en upplevelse få personer kan föreställa sig. Syftet är att beskriva upplevelsen hos vuxna individer som väntar på transplantation av livsviktiga organ; lever, hjärta och lunga. Denna litteraturstudie bygger på nio kvalitativa vetenskapliga artiklar som har sökts fram av författarna i väsentliga referensdatabaser. Data analyserades enligt Axelssons (2012) modell för litteraturstudier. Studien resulterade i sex teman samt sex subteman. Resultatet visar hur individer i behov av organtransplantation upplever väntan på operation, samt vad sjuksköterskans roll har betytt i omvårdnaden. En upplevelse av ovisshet och maktlöshet var framträdande, men även hopp och glädje. Hos sjuksköterskan och övrig vårdpersonal önskas och behövs en förståelse för vad individer som väntar på organtransplantation upplever och genomgår. Detta för att i mötet kunna ge bästa möjliga stöd och omvårdnad. Sjuksköterskans information till individerna som väntar på organtransplantation samt dess närstående visade sig vara betydelsefull. Likaså visar studien hur och varför sjuksköterskans stöd under väntan på organtransplantation var av vikt för dessa individers upplevelser. / Program: Sjuksköterskeutbildning

Njuren är det organ som är vanligast att transplantera och det är även det organ flest personer står på väntelistan för att transplantera. Njuren har en viktig funktion i regleringen av kroppsvätskorna och den har även en viktig endokrin funktion. Efter transplantationen förändras vardagen för den transplanterade. Syftet med litteraturstudien är att belysa patientens upplevelse av att leva som njurtransplanterad de första åren efter transplantation. Litteraturstudien är baserad på analyser från nio vetenskapliga artiklar med kvalitativ ansats. Artiklarna har analyserats utifrån Axelssons modell. Resultatet presenteras i form av tre huvudteman med vardera tre subteman. Huvudtemat den njurtransplanterades livsvärld beskrivs med subteman som livskvalitet, tacksamhet och socialt sammanhang. Huvudtemat den njurtransplanterades levda kropp beskrivs med subteman rädsla för bortstötning av njuren, biverkningar och förändrad subjektiv kropp. Det tredje huvudtemat behov av lärandestöd hos den njurtransplanterade beskrivs med subteman lärandebehov, hanterbarhet och ansvar. Diskussionen belyser transplanterades behov av stöd och information. Det förs även en diskussion angående den starka tacksamhet de transplanterade känner efter transplantationen och deras upplevelse av svårighet att uttrycka denna tacksamhet i ord. För att sjuksköterskan ska kunna stötta transplanterade och dess närstående är det viktigt att identifiera deras individuella behov av information och stöd. Slutsatsen av litteraturstudien visar att det finns många gemensamma upplevelser av att leva med en ny njure som berör livsvärlden, den levda kroppen och behovet av lärandestöd. / Program: Sjuksköterskeutbildning

Det är idag mellan 700 – 800 patienter som väntar på ett nytt organ i Sverige. Dock är tillgången på organ betydligt mindre än efterfrågan, vilket leder till att väntan på ett nytt organ kan bli mycket lång. För en del patienter orkar inte kroppen med den långa väntan vilket leder till en för tidig död. Att vänta på ett nytt organ innebär ett stort lidande för patienten. Ovissheten om vad som kommer att hända i väntan på det nya organet och hur man hanterar sin livssituation i detta läge är avgörande för patientens välbefinnande.Syftet med denna litteraturstudie är att belysa patienters upplevelser av att vänta på ett nytt organ. Studien bygger på analys av kvalitativ forskning. Metoden har valts utifrån syftet att belysa patienters upplevelser. Resultatet presenteras utifrån tre huvudteman: Förlorad kontroll, väntans emotioner och att hantera vardagen. Dessa teman beskriver, utifrån tillhörande subteman, hur patienter upplever väntan på ett nytt organ. Resultatet vittnar om att det är många aspekter av att vänta på ett nytt organ som bidrar till ett lidande. Resultatet visar att väntan på ett nytt organ är en väldigt omtumlande upplevelse som påverkar patienten såväl fysiskt som psykiskt. Livet blir begränsat i många avseenden på grund av sjukdomens svåra symtom samt ovissheten om framtiden. Hur patienten klarar av att hantera denna svåra livssituation beror såväl på stöd från omgivningen som personliga strategier i form av coping. / Program: Sjuksköterskeutbildning

Kronisk njursvikt kan idag endast botas med njurtransplantation, där donationen ofta sker från en levande donator som genomgår en omfattande hälsoundersökning för att få donera. Utifrån den subjektiva kroppen ger donatorn en bit av sig själv och därmed kan både hans/hennes identitet och livsvärld förändras, vilket kan ge ett lidande. Med den här kunskapen kan sjuksköterskan bli medveten om lidandet och både bemötandet och vården kan därmed förbättras för donatorn. Syftet med den här litteraturstudien är att belysa njurdonatorers upplevelser av att donera en av sina njurar. Med en systematisk sökning i databaser blev resultatet åtta kvalitativa artiklar som svarade an mot syftet. Artiklarna granskades avseende kvalitet. Evans (2002) metod för beskrivande syntes användes och fyra nya teman med tillhörande subteman uppstod. Resultatet beskriver donatorers motiv för att donera, som att se den blivande mottagaren bli sämre i sin sjukdom och viljan att återupprätta hälsan hos mottagaren. När donatorerna beslutat sig för att donera förberedde de sig mentalt inför operationen och det kunde då uppstå främmande känslor och rädslor. Det framkommer även att donatorns livsvärld förändras efter donationen, dels glädjen över att gett någon hälsa åter men även lidande i form av smärta, trötthet och känslor av förlust. Många donatorer ville att deras relation till mottagaren skulle vara densamma som innan donationen men relationen blev för många istället starkare. Vårdrelationen framställs av flera som positiv men det förekommer också att donatorer upplevde att de inte fick bekräftelse från vårdpersonalen. Diskussionen behandlar donatorns lidande i samband med donationen. Det talas om hur intimiteten till mottagaren kan påverka donatorns vilja att donera. / Program: Sjuksköterskeutbildning

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