Mycophenolate mofetil (MMF) is widely used to minimise acute rejection following solid organ transplantation as it inhibits inosine monophosphate dehydrogenase (IMPDH) and thereby reduces lymphocyte activation. The effects of MMF and azathioprine on renal allograft outcome were examined by analysis of the national transplant database held at National Health Service (NHS) Blood and Transplant, Stoke Gifford, Bristol, UK. In a paired kidney analysis, MMF treated patients had a 3 year death censored graft survival of 91% (n=217) contrasts to 97% (n=231) in azathioprine treated patients (p=0.07) with an increased acute rejection rate in the first year after transplantation (44 v 31%, n=105 v 74, p<0.01). In a further study, 13% (n=71) of patients were found to be taking less than 1 g of MMF which was associated with a 3-fold increased risk of graft failure and inferior graft function up to 36 months. One strategy to improve graft outcome would entail targeting MMF dose according to pre-transplant IMPDH activity, which is known to display wide variability between patients, in order to maximize efficacy and minimize toxicity. Therefore, it was decided to measure pre-transplant IMPDH activity and to investigate associations with renal allograft outcome and MMF dose tolerated after transplantation. IMPDH activity was measured by detection of generated XMP by a validated HPLC method in the peripheral mononuclear cells of 55 patients waiting for renal transplantation and was found to exhibit a 4-fold variation of IMPDH activity. Black males had significantly increased IMPDH activity contrasts to Black females (p=0.01). Within the first year of transplantation, 71% (n=12) patients required a reduction in MMF dose. There was no association between pre-transplant IMPDH activity and MMF dose achieved at 1 year or MMF associated side effects or eGFR up to 36 months. It was proposed that the inter-individual variability of IMPDH activity may be associated with genetic polymorphisms and therefore sequencing of the exons of IMPDH I and II was undertaken. Two novel single nucleotide polymorphisms (SNPs), Leu244Leu and Ala285Thr, were identified in the IMPDH I gene. Patients with these variants did not exhibit differential IMPDH activity. Genotyping for established intronic SNPs was undertaken in our patient cohort as well as a random sample of 1040 recipients from the Collaborative Transplant Study DNA bank based at the University of Heidelberg, Germany. The presence of these SNPs did not increase the risk of rejection or affect graft function or MMF dose tolerated at 1 year after transplantation and there was no association between pre-transplant IMPDH activity, 5 year graft and patient survival and genotype. In our study, MMF treatment did not result in improved renal allograft outcomes in comparison to azathioprine therapy. Furthermore, we suggest that measurement of pre-transplant IMPDH activity or genotyping of the IMPDH enzymes is unlikely to assist in optimizing MMF dose and renal allograft outcome.

Entwicklungen im Bereich der Medizin führen immer wieder zu einer Neuformulierung der Grenze zwischen Leben und Tod. Jüngere Skandale um die Vergabe von Spenderorganen sorgen für Diskussionen um die ethischen Grundlagen der Transplantationspraxis, zu denen die Definition des Hirntodes gehört. Zur Auseinandersetzung mit ethischen Fragen gehört, den eigenen Kulturraum näher zu betrachten und zu analysieren. Der chinesische Kulturraum soll dabei als Vergleichsebene dienen, sich mit einem anderen Zugang zu und einem anderen Verständnis von Bioethik zu beschäftigen. Die Disziplin der Bioethik im chinesischen Kulturraum ist zwar noch eine sehr junge, kann aber auf eine eigenständige Medizintradition (Traditionelle Chinesische Medizin) zurückgreifen. Dieser bioethischen Analyse liegen entsprechend alte Denktraditionen des Konfuzianismus, Buddhismus und Daoismus zugrunde. Die vorliegende Arbeit beinhaltet den ethisch-kulturellen Vergleich zwischen Deutschland und der Volksrepublik China, die Suche nach Unterschieden und Gemeinsamkeiten im Umgang mit Organtransplantation und Hirntodkonzept. Dabei geht es zum einen um die direkte Gegenüberstellung der gesetzlichen Regelungen, zum anderen erfolgt eine deskriptive-ethische Analyse auf Grundlage der vier Diskussionsebenen – diagnostische Tests, Todeskriterium, Todesdefinition, Menschenbild – um das Hirntodkonzept in beiden Ländern

ABSTRAKT Bakgrund: Ett nytt organ är livräddande behandling för patienter med kroniska hjärt- eller leversjukdomar. För den som blir transplanterad innebär det en stor omställning i livet, från att ha varit kronisk sjuk till att leva med ett nytt organ. Efter en transplantation är målet att personen ska kunna återgå till ett normalt liv. Syfte: Syftet med litteraturstudien var att belysa den transplanterades perspektiv på att leva med ett nytt organ. Metod: I litteraturstudien har tio kvalitativa studier granskats och analyserats med inspiration av innehållsanalys. Artikelsökning gjordes i Cinahl, PubMed och PsycInfo. Resultat: I resultatet framkom tre huvudkategorier: ”Förändrad kropp”, ”Känslomässig berg- och dalbana” och ”Att leva vidare”. Under dessa framkom åtta underkategorier. Slutsats: Att genomgå en organtransplantation är en livsomvälvande upplevelse som förändrar livet för alltid. För sjuksköterskan är det viktigt att vara medveten om patientens perspektiv för att kunna ge god och anpassad omvårdnad. Trots att transplantationen följs av en påfrestande återhämtning både fysiskt och psykiskt så ges man genom ett nytt organ en andra chans i livet och hopp om en bättre framtid.   Nyckelord: Organtransplantation, patientperspektiv, omvårdnad / ABSTRACT Background: A new organ is a lifesaving treatment for patients living with chronicle illness in heart or liver. To be transplanted implicates a big change in life, from living with a chronicle illness to be living with a new organ. After the transplantation the aim for the patient is to go back to living a normal life again. Aim: The aim of this literature review was to elucidate the transplanted patient perspective of living with a new organ. Method: In this literature review ten qualitative studies were viewed and analysed. The articles were searched in CINAHL, PubMed and PsycInfo.  Result: The result identified three main categories: ”Changed body”, ”Emotional rollercoaster” and ”To manage to keep living”. From these categories eight sub categorize were identified. Conclusion: To be transplanted is a life changing experience that changes the life forever. It is important for the nurse to be aware of the patient perspective to be able to offer a good and suitable care for the patient. Though the transplantation is followed by a difficult recovery, both physical and psychological, to be transplanted gives you a second chance in life and hope of a better future. Keywords: Organ transplantation, patient perspective, nursing

No description available.

Organtransplantation erbjuds till patienter med livshotande organsvikt när det inte finns någon annan medicinsk eller kirurgisk behandling som kan förbättra tillståndet. Att motta ett organ är en livsförändrande upplevelse för en patient. Patienter och deras familj behöver vägledning, medkänsla och stöd från sjuksköterskor. Eftersom en transplantation är ett stort och avancerat kirurgiskt ingrepp behöver patienter omfattande omvårdnadsinsatser innan, under och efter ingreppet. Sjuksköterskans ansvar är att stödja patienter i denna process och därför är det av vikt att studera hur en transplantation upplevs av patienter. Syftet med litteraturstudien var att beskriva upplevelser av att vara patient i samband med en organtransplantation. Metoden var en litteraturstudie som bestod av tio resultatartiklar. Fyra teman framträdde i resultatet: Upplevelser av information, Upplevelser av stöd, Upplevelser av förlorad kontroll och Upplevelser av en andra chans i livet. Att genomgå en organtransplantation förändrar livet för patienter på många olika sätt. För att kunna hantera denna förändring krävs hjälp från sjukvården. Sjuksköterskor som jobbar med organtransplanterade patienter behöver större förståelse för denna patientgrupps situation för att bättre kunna bemöta deras behov. / Organ transplantation is offered to patients with a life-threatening illness when there is no other medical or surgical treatment that can improve their condition. To receive an organ is a life changing experience for a patient. Patients and their families need guidance, compassion and support from nurses. Since a transplantation is a large surgery, patients need nursing care before, under and after the surgery. In order to support patients in this process it is important for nurses to study how a transplant is experienced. The aim of the study was to describe experiences of being an organ transplant patient. The method was a literature study consisting ten articles. Four categories appeared in the result, Experiences of information, Experiences of support, Experiences of loss of control and Experiences of getting a second chance. To go through an organ transplantation is a life changing experience for a patient in many different ways. To be able to manage this, patients need help from healthcare teams. Nurses need to understand this patient group better in order to improve their care.

Made available in DSpace on 2015-07-22T20:50:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-08-26. Added 1 bitstream(s) on 2015-08-11T03:26:28Z : No. of bitstreams: 1 Publico-322.pdf: 393779 bytes, checksum: e3edd8a910aaf2a4ada36110dfd5e404 (MD5) / Introdução: As polimixinas são antimicrobianos antigos, e que caíram em desuso por muitos anos pelos relatos de toxicidade, principalmente nefrotoxicidade e neurotoxicidade. O surgimento de bactérias gram negativas multirresistentes em especial P aeruginosa e A baumanii em todo o mundo é uma realidade e temos observado seu crescimento em inquéritos epidemiológicos internacionais a partir dos anos 90. Não há estudos que demonstrem a taxa de disfunção renal nos pacientes transplantados pelo uso da polimixina, porém sabe-se que a função renal contribui de forma estatisticamente significante para a sobrevida dos receptores a longo prazo. Métodos: Foram levantados retrospectivamente os prontuários de todos os pacientes transplantados de órgãos sólidos, e que utilizaram polimixinas, durante o período janeiro 2001 a dezembro 2007 em 2 hospitais de ensino na cidade de São Paulo, Brasil. O objetivo principal do estudo foi definir o percentual de nefrotoxicidade apresentado pelos pacientes. Com o objetivo de avaliar essa variável escolhemos 2 definições de toxicidade renal (critério 1 e critério 2) e as aplicamos em todos os pacientes estudados com o objetivo de compará-las entre si e com a literatura. Critério 1 foi definido como creatinina sérica > 2 mg/dl após introdução da polimixina em pacientes com disfunção renal aguda, ou aumento de 50% da creatinina sérica em relação aos valores pré-polimixina naqueles com disfunção renal prévia. Associa-se à definição em qualquer das 2 situações acima a diminuição do clearance de creatinina estimado pela metodologia de Cockcroft & Gault em 50%, ou evolução para terapia dialítica. Critério 2 foi definido como qualquer aumento de creatinina sérica. Resultados: Foram identificados 92 pacientes transplantados de órgãos sólidos que utilizaram polimixinas. Em sua maioria eram transplantados de rim, ou rim/pâncreas (90,2%), cujo enxerto foi recebido de doador falecido em 70,7% dos casos. O principal diagnóstico foi infecção do trato urinário (ITU) (41,3%), seguido de infecção do sítio cirúrgico (17,4%), e pneumonia (16,3%). P aeruginosa foi o agente etiológico mais freqüente, presente em 76,1% dos isolados. Houve cura microbiológica em 25 pacientes (100%), cura clínica de 71 pacientes (77,2%), e mortalidade hospitalar em 21 pacientes (22,8%). Quarenta e quatro pacientes (47,8%) apresentaram nefrotoxicidade por qualquer dos 2 critérios adotados, 30 pacientes (32,6%) pelo critério 1, e 44 pacientes (47,8%) pelo critério 2. A análise multivariada demonstrou associação estatisticamente significante entre ITU e proteção para nefrotoxicidade [p 0,02; OR 0,24; IC 95% (0,07 – 0,86)] e média de tempo de utilização da polimixina maior como fator de risco para disfunção renal [p 0,03; OR 1,06; IC 95% (1,0 – 1,13)] pelo critério 1. Conclusão: A taxa de disfunção renal de 32,6% ainda é alta, porém menor que as inicialmente descritas na década de 60 e 70. A utilização da polimixina é eficaz principalmente no tratamento de ITU em pacientes transplantados de órgãos sólidos. A utilização de polimixina deve ser realizada por menor tempo possível e, quando não existir outro antimicrobiano possível. / Introduction: Polymyxins are old antimicrobials which had their use discontinued for many years because of nephrotoxicity and neurotoxicity description. The development of multirresistant gram negative bacteria in special P aeruginosa and A baumanii all over the world is a matter of fact and we have observed its growth in international epidemiologic surveys since the 90’s. Until now we don´t have studies that demonstrate renal dysfunction tax in transplanted patients because of polymyxin use, nevertheless we know that renal function contribute in a statistical significant manner for receptors survive in long term. Methods: We have retrospectively searched for all solid organ transplanted patients and who have used polymyxins from January 2001 to December 2007 in 2 teaching hospitals in São Paulo city, Brazil. The main study objective was to define the nephrotoxicity percentage. For evaluating this variable we choosed 2 renal function definitions (first criteria and second criteria) and applied them in all studied patients with the objective of comparing them each other and with the literature. First criteria was defined as serum creatinine > 2 mg/dl after polymyxin introduction in those patients with acute renal dysfunction, or 50% serum creatinine increase in relation to value before polymyxin was given in those patients with previous nephotoxicity. In both situations described above we also considered renal dysfunction if 50% decrease in estimated creatinine clearance by Cockcroft & Gault methodology occurred, or progression to dialysis therapy. Second criteria was defined as any serum creatinine increase. Results: We identified 92 solid organ transplanted patients who used polymyxins. The majority of them received renal or renal/pancreas grafts (90.2%), and the organs transplanted were from deceased donors in 70,7%. The main site of infection were urinary tract infection (UTI) (41.3%), followed by surgical site infection (SSI) (17.4%) and pneumonia (16.3%). P aeruginosa were the main etiologic agent present in 76.1% of isolates. Microbiologic cure occurred in 25 patients (100%), clinical cure in 71 patients (77.2%), and in hospital mortality occurred in 21 patients (22.8%). Fourty four patients (47.8%) presented nephrotoxicity according to any of the 2 adopted criteria, 30 patients (32.6%) according to the first criteria, and 44 patients (47.8%) according to the second criteria. Multivariate analysis show statistical significant association among UTI and protection for renal dysfunction [p 0.02; OR 0.24; IC 95% (0.07 – 0.86)], and greater mean polymyxin utilization time (p 0.03) as a risk factor for renal dysfunction by the first criteria. Conclusions: The 32.6% percentage of renal dysfunction is still high, but lower than that reported in the 60’s and 70’s. Polymyxin utilization is effective principally for the treatment of UTI in solid organ transplanted patients, its use should be judicious and for shorter time as possible. / TEDE / BV UNIFESP: Teses e dissertações

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Objetivou-se analisar a prÃtica dos Enfermeiros de terapia intensiva junto ao paciente potencial doador de ÃrgÃos e tecidos. Trata-se de uma pesquisa exploratÃria, descritiva e analÃtica, com abordagem qualitativa. O estudo foi realizado em um Centro de Terapia Intensiva (CTI) clÃnico de um hospital pÃblico estadual em Fortaleza - CE. Os sujeitos do estudo foram 30 Enfermeiros que atuam no serviÃo. A produÃÃo de dados ocorreu entre agosto e dezembro de 2013, apÃs aprovaÃÃo pelo Comità de Ãtica em Pesquisa da InstituiÃÃo, conforme Parecer n 376.423. Os dados deste estudo foram produzidos atravÃs de entrevista e a partir da observaÃÃo sistemÃtica. Na anÃlise do material optamos pela tÃcnica de anÃlise de conteÃdo, modalidade temÃtica, segundo Bardin (2011). Para a ordenaÃÃo do material empÃrico e constituiÃÃo do corpus, aplicamos a tÃcnica de anÃlise categorial. O processo de anÃlise e discussÃo foi construÃdo com base no discurso do Enfermeiro do CTI, nas informaÃÃes da observaÃÃo e diÃrio de campo. O processo de anÃlise e discussÃo iniciou-se com o agrupamento e classificaÃÃo do material produzido em quatro categorias e dez subcategorias. As categorias definidas foram: O processo de doaÃÃo de ÃrgÃos; DimensÃes do cuidado do Enfermeiro ao paciente potencial doador; PercepÃÃo do Enfermeiro sobre a sua prÃtica junto ao paciente potencial doador de ÃrgÃos e tecidos; Impacto da assistÃncia do Enfermeiro na concretizaÃÃo da doaÃÃo de ÃrgÃo e tecidos. A observaÃÃo sistemÃtica da assistÃncia dos Enfermeiros ao potencial doador de ÃrgÃos foi utilizada como contra ponto ao discurso dos sujeitos ao definirem sua prÃtica junto ao paciente e sua famÃlia. A percepÃÃo dos Enfermeiros acerca do processo de doaÃÃo de ÃrgÃos està permeada por questÃes culturais, filosÃficas, Ãticas e emocionais, relacionadas ao: significado da doaÃÃo de ÃrgÃos; falta de capacitaÃÃo tÃcnico-cientÃfica; dificuldades emocionais de lidar com o paciente e com a famÃlia. O processo de doaÃÃo de ÃrgÃos e tecidos à complexo e, muitas vezes, difÃcil para os envolvidos. Constatamos que o Enfermeiro, apesar de reconhecer que nÃo possui formaÃÃo tÃcnica especÃfica para atuar junto a este tipo de clientela, considera que desempenha um papel determinante no processo doaÃÃo-transplante. Em sua prÃtica, desenvolve o cuidado voltado, principalmente, para a monitorizaÃÃo e manutenÃÃo hemodinÃmica e, tambÃm, para orientar e acolher os familiares, considerando que todos estes cuidados podem ser determinante ao sucesso da concretizaÃÃo da doaÃÃo. As dificuldades vivenciadas pelo Enfermeiro tÃm repercussÃes pessoais que influenciam em sua saÃde fÃsica e emocional, e, tambÃm, na qualidade da assistÃncia ou desassistÃncia ao paciente e sua famÃlia. A aproximaÃÃo da realidade estudada nos permitiu conhecer um pouco da prÃtica complexa e multifacetada, desenvolvida pelo Enfermeiro, em um ambiente tenso e crÃtico, onde a dor, o sofrimento, a morte, a vida, a esperanÃa, a inseguranÃa e tantos outros sentimentos, se misturam e se dimensionam na individualidade de cada profissional e do paciente e da sua famÃlia.

Introduktion/Bakgrund: Transplantation är en livräddande behandling som erbjuds när ingen annan behandling leder till förbättrat tillstånd. Organbristen är idag större än utbudet som finns för organ. Väntelistan för att få ett nytt organ är lång och som konsekvens av detta kan individer avlida innan transplantation. Det finns levande och avlidna donatorer, där levande donatorer behöver öka i antal för att utveckla möjligheten till fler organtransplantationer. Det är angeläget att sjuksköterskan tillgodoser andliga, existentiella, sociala och psykiska behov i lika stor utsträckning som fysiska behov avseende omvårdnadsinterventioner. Syfte: Undersöka hur individer beskriver väntan på en organtransplantation. Metod: Litteraturstudien har framställts genom Polit och Beck’s (2017) nio steg och är systematiskt utformad genom datainsamling från databaserna Cinahl, PubMed och PsycINFO. Resultatet inkluderar elva vetenskapliga artiklar, varav nio kvalitativa och två kvantitativa studier. Resultat: I litteraturstudien identifierades fyra kategorier; en evig kamp, brist på frihet, det okända och livet med andra som beskriver väntan. Slutsats: Litteraturstudiens resultat beskriver upplevelser av både negativ och positiv karaktär. Begränsningar i livet är främst vad som påverkar välbefinnandet hos individer och bidrar även till psykologiska utmaningar. Väntetiden är en individuell upplevelse där information och stöttning från sjuksköterskan är angeläget för att förebygga ohälsa.

Most South Africans die without their organs being harvested for transplantation. In a country where motor vehicle accidents or violent crime are often the cause of death, presumably leaving most of the organs fit for transplantation, it is astounding that the offer of organs doesn’t meet the demand. The aim of this dissertation is to find a practical solution for the current shortage of transplantable human organs in South Africa. This is achieved by critically discussing current South African legislation regulating organ transplantation, considering alternative organ procurement methods, as well as the impact that bioethics and the Constitution might have on the success of an organ procurement system. This dissertation is concluded with the realisation that although the current organ procurement method needs to be changed to required request, relieving the organ shortage will only be achieved by combining several proposed legislative changes, including, but not limited to, creating a national donor as well as a national waiting list; launching an educational campaign; limiting the role of relatives; and expanding the definition of death for the purpose of organ harvesting. KEY TERMS: organ procurement methods; National Health Act; Constitution; organ shortage; bioethics; autonomy; dignity; required request. / Dissertation (LLM)--University of Pretoria, 2013. / gm2014 / Public Law / unrestricted

Organ transplantation is one of the most important and effective solutions to save end-stage patients, who have one or more critical organ failures. However, the inadequate organs for transplantation to meet the demands has been the major issue. Even worse, the lack of accurate non-invasive assessment methods wastes 20% of donor organs every year. Currently, the most frequently used organ assessment methods are visual inspections and biopsy. Yet both methods are subjective: the assessment accuracy depends on the evaluator's experience. Moreover, repeating biopsies will potentially damage the organs. To reduce the waste of donor organs, online non-invasive and quantitative organ assessment methods are in great needs. Organ viability assessment is a challenging issue due to four reasons: 1) there are no universally accepted guidelines or procedures for surgeons to quantitatively assess the organ viability; 2) there is no easy-deployed and non-invasive biological in situ data to correlate with organ viability; 3) the organs viability is difficult to model because of heterogeneity among organs; 4) both visual inspection and biopsy can be applied only at present time, and how to forecast the viability of similar-but-non-identical organs at a future time is still in shadow. Motivated by the challenges, the overall objective of this dissertation is to develop online non-invasive and quantitative assessment methods to predict and forecast the organ viability. As a result, four data-driven modeling research tasks are investigated to achieve the overall objective: 1) Quantitative and qualitative models are used to jointly predict the number of dead cells and the liver viability based on features extracted from biopsy images. This method can quantitatively assess the organ viability, which could be used to validate the biopsy results from pathologists to increase the evaluation accuracy. 2) A multitask learning logistic regression model is applied to assess liver viability by using principal component analysis to extract infrared image features to quantify the correlation between liver viability and spatial infrared imaging data. This non-invasive online assessment method can evaluate the organ viability without physical contact to reduce the risk of damaging the organs. 3) A spatial-temporal smooth variable selection method is conducted to improve the liver viability prediction accuracy by considering both spatial and temporal effects from the infrared images without feature engineering. In addition, it provides medical interpretation based on variable selection to highlight the most significant regions on the liver resulting in viability loss. 4) A multitask general path model is implemented to forecast the heterogeneous kidney viability based on limited historical data by learning the viability loss paths of each kidney during preservation. The generality of this method is validated by tissue deformation forecasting in needle biopsy process to potentially improve the biopsy accuracy. In summary, the proposed data-driven methods can predict and forecast the organ viability without damaging the organ. As a result, the increased utilization rate of donor organs will benefit more end-stage patients by dramatically extending their life spans. / Doctor of Philosophy / Organ transplantation is the ultimate solution to save end-stage patients with one or more organ failures. However, the inadequate organs for transplantation to meet the demands has been the major issue. Even worse, the lack of accurate and non-invasive viability assessment methods wastes 20% of donor organs every year. Currently, the most frequently used organ assessment methods are visual inspections and biopsy. Yet both methods are subjective: the assessment accuracy depends on the personal experience of evaluator. Moreover, repeating biopsies will potentially damage the organs. As a result, online non-invasive and quantitative organ assessment methods are in great needs. It is extremely important because such methods will increase the organ utilization rate by saving more discarded organs with transplantation potential. The overall objective of this dissertation is to advance the knowledge on modeling organ viability by developing online non-invasive and quantitative methods to predict and forecast the viability of heterogeneous organs in transplantation. After an introduction in Chapter 1, four research tasks are investigated. In Chapter 2, quantitative and qualitative models jointly predicting porcine liver viability are proposed based on features from biopsy images to validate the biopsy results. In Chapter 3, a multi-task learning logistic regression model is proposed to assess the cross-liver viability by correlating liver viability with spatial infrared data validated by porcine livers. In Chapter 4, a spatial-temporal smooth variable selection is proposed to predict liver viability by considering both spatial and temporal correlations in modeling without feature engineering, which is also validated by porcine livers. In addition, the variable selection results provide medical interpretations by capturing the significant regions on the liver in predicting viability. In Chapter 5, a multitask general path model is proposed to forecast kidney viability validated by porcine kidney. This forecasting method is generalized to apply to needle biopsy tissue deformation case study with the objective to improve the needle insertion accuracy. Finally, I summarize the research contribution and discuss future research directions in Chapter 6. The proposed data-driven methods can predict and forecast organ viability without damaging the organ. As a result, the increased utilization rate of donor organs will benefit more patients by dramatically extending their life spans and bringing them back to normal daily activities.