Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on July 16, 2010). Includes bibliographical references (p. 90-105).

A desnutrição freqüentemente está presente em pacientes com insuficiência cardíaca (IC), podendo trazer aumento de complicações e mortalidade. O objetivo do estudo foi o de avaliar o estado nutricional de pacientes portadores de IC refratária, aguardando a realização de transplante cardíaco. Avaliação nutricional foi realizada utilizando-se da avaliação subjetiva global, avaliação antropométrica completa [índice de massa corpórea (IMC), circunferência do braço (CB), prega cutânea tricipital (PCT), circunferência muscular do braço (CMB) e área gordurosa do braço (AGB)], avaliação laboratorial e realização de anamnese alimentar em dois momentos: no momento de admissão na fila de transplante (1a avaliação) e 4 meses após (2a avaliação). Na 1ª avaliação foram estudados 56 pacientes, idade média de 46±12 anos, 67,8% homens, 33,9% com miocardiopatia chagásica. Análise de dados antropométricos revelou com base no IMC: 73,2% eutróficos e 5,3% com baixo peso; CMB: 66% apresentavam depleção. Houve correlação negativa e significativa entre IMC e fator de necrose tumoral (r= - 0,305; p= 0,022). Análise laboratorial demonstrou: baseado na albumina, 50% dos pacientes apresentavam-se com algum grau de depleção, na transferrina 40% e na contagem de linfócitos 80%. Houve correlação negativa e significativa entre albumina e interleucina-6 (r = - 0,464; p< 0,001), transferrina e interleucina-6 (r= -0,269; p= 0,047) e contagem de linfócitos e interleucina-6 (r= - 0,394; p=0,003). Na 2ª avaliação 18 pacientes foram estudados. Não foram observadas diferenças significativas entre as duas avaliações quanto aos parâmetros estudados. Com base na realização da anamnese alimentar os pacientes atingiram aproximadamente 85% e 84% de suas necessidades calóricas na 1ª e 2ª avaliações, e com relação à ingestão protéica, tanto na 1ª como na 2ª avaliação mais de 70% dos pacientes apresentaram consumo adequado de proteínas. Foi observado consumo abaixo das necessidades nutricionais de cálcio, potássio, magnésio, zinco, folato e vitamina E. Quanto ao sódio verificamos um consumo acima do recomendado. Foram transplantados 14 pacientes com idade de 44 ± 21 anos, 57,1% do sexo masculino, quatro pacientes morreram no pós operatório. Não houve diferenças significativas quanto aos dados antropométricos, laboratoriais, de adequação alimentar e idade entre o grupo de transplantados que sobreviveram (n=9) comparados com os que faleceram (n=4). Concluímos que a desnutrição é comum em pacientes com IC grave aguardando transplante cardíaco. A avaliação nutricional baseada no IMC não mostrou ser um bom método, necessitando ser complementada com as medidas de CB, CMB, PCT e AGB. A avaliação laboratorial permitiu a detecção de comprometimento nutricional. A participação das citocinas inflamatórias no processo de desnutrição foi evidenciada em nossa população. Portanto, a avaliação nutricional completa deve fazer parte do atendimento em pacientes com IC crônica, particularmente aqueles com IC refratária à espera por um transplante cardíaco / Malnutrition is frequently present in patients with heart failure (HF) and is associated with an increase in morbidity and mortality. The objective of this study was to evaluate nutritional status of patients with refractory HF waiting for cardiac transplantation. Nutritional evaluation was done with the use of subjective global assessment, complete anthropometric measurements (body mass index (BMI), mid-arm circumference (MAC), triceps skinfold thickness (TSF), mid-arm muscle circumference (MAMC) and arm fat area), laboratory evaluation and food intake assessment in two moments: at the admission to the cardiac transplantation waiting list (1st evaluation) and after 4 months (2nd evaluation). On the 1st evaluation, we studied 56 patients, mean age 46±12 years, 67.8% were men, and 33.9% had Chagas disease. Analyzing anthropometric measurements, we found that, based on BMI 73.2% of patients were normal and 5.3% had underweight; MAMC revealed 66% with depletion. There was a negative and significant correlation between BMI and tumor necrosis factor-a (r= - 0.305; p<0.022). Laboratory evaluation showed that based on albumin levels, 50% of patients had some degree of depletion, based on transferrin 40% and on lymphocyte count 80%. There were negative and significant correlations between albumin and interleukin-6 (r= - 0.464; p<0.001), transferrin and interleukin-6 (r= -0.269; p<0.047) and lymphocyte count and interleukin-6 (r= -0.394; p<0.003). On the 2nd evaluation 18 patients were studied. There were no significant differences in the studied parameters between the 1st and 2nd evaluations. Based on the food intake assessment, percentage of adequacy of calories intake was 85% and 84% on 1st and 2nd evaluations, and more than 70% of patients had adequate protein intake on both evaluations. Low intake of calcium, potassium, magnesium, zinc, folate and vitamin E was detected. Daily sodium intake was found to be above the recommended levels. Fourteen patients were submitted to cardiac transplantation, mean age 44±21 years, 57.1% were men. Four patients died in post operative period. No relation was observed between anthropometric, laboratory, alimentary adequacy and age variables between patients transplanted that survive (n=9) and that died (n=4). We concluded that malnutrition is common in patients with refractory HF listed for cardiac transplantation. Nutritional assessment based on BMI did not show to be a good index to detect nutritional disorders and need to be used together with MAC, TSF, MAMC and arm fat area. Laboratory evaluation permitted the detection of compromised nutritional status. The participation of inflammatory cytokines in the process of malnutrition was evidenced in our population. Therefore, a complete nutritional evaluation should be part of routine care of patients with chronic HF, particularly in those with refractory HF waiting for cardiac transplantation

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

Heart transplantation (HTx) is now an established therapy for end-stage cardiac failure not responding to medical treatment. Recent decades have seen improved outcome following HTx due to more effective and targeted immunosuppressive therapy. However, acute and chronic rejection remains a major cause of morbidity and mortality. At the same time, immunosuppressive strategies are associated with significant side effects, including development of tumours. Hence, the induction of immunologic tolerance to alloantigen is considered the “holy grail” of transplant research. T regulatory cells (Tregs) are a subset of T cells that appear to suppresscytotoxic cell and initiate tolerance to foreign tissues. The Tregs suppresscytotoxic cells through specific cytokine pathways and cell-cell contact. In-vivo T reg migration has been a matter of debate in recent years. Treg trafficking is governed by chemokines, which are small secreted proteins, acting via their distinct trans-membrane serpentine receptors. Experimental work has demonstrated an involvement of distinct chemokine pathways in Tregs migration and localization following cardiac transplantation; however, there is paucity of data in humans. I investigated the effects of chemokines on Tregs in heart transplant recipients through a series of observational studies. My study demonstrated that acute rejection following heart transplantation is associated with a significant elevation of peripheral blood Th1 chemokine levels. I hereby further show that peripheral blood Treg counts in stable heart transplant recipients are not affected by immunosuppression but are significantly lower in patients taking statins. I have demonstrated via in-vitro chemotaxis assays a specific pattern of chemotactic response for Tregs and the effector T cells. Using double immunofluorescence staining and immunostaining, I show for the first time that Tregs may migrate to the allograft under the influence of CCL17.

This is a study of some of the families in the Loma Linda University Medical Center infant heart transplant program.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13428号 / 論医博第2232号 / 新制||医||1053(附属図書館) / (主査)教授 湊谷 謙司, 教授 佐藤 俊哉, 教授 福田 和彦 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Bakgrund: Hjärttransplantation har utförts sedan 1960-talet och är idag det sista behandlingsalternativet vid svår och icke behandlingsbar hjärtsvikt. Efter en hjärttransplantation följer en livslång medicinering för att minimera risken för avstötningar. Patienterna behöver gå på regelbundna återbesök för att styra läkemedeldosering och för att förebygga biverkningar. Sjuksköterskan har en central roll i vården av hjärttransplanterade patienter. Det är viktigt att sjuksköterskan har kunskap om hur dessa patienter upplever livet efter hjärttransplantationen, för att kunna vara ett stöd och ge patienterna en adekvat personcentrerad vård. Sjuksköterskans ansvar är att även informera patienterna och dess anhöriga kring hjärttransplantationer. Syfte: Syftet var att beskriva patienters upplevelse av att leva med ett transplanterat hjärta. Metod: Litteraturöversikten baseras på tio vetenskapliga artiklar. Artiklarna har analyserats och tematiserats med färgkodning. Databaserna CINAHL Complete och PubMed användes för att söka fram artiklarna. Enbart kvalitativa artiklar refereras till i resultatet. Resultat: I resultatet redovisades i fyra teman. Dessa fyra teman: Livet efter en hjärttransplantation innebar förändrade fysiska förmågor, Livet med ett nytt hjärta innebar blandade känslor, Livet efter hjärttransplantation påverkas av donatorn och Ett liv med ett nytt hjärta innebar ett stödbehov. Resultatet visade att patienternas vardagliga liv hade påverkats både fysiskt och psykiskt i samband med hjärttransplantationen. Patienterna uttryckte detta med olika motstridiga känslor såväl positiva och negativa. Behov av stöd från familjen, vårdteam och tron hade stor betydelse i patienternas anpassning till deras nya liv. Desto bättre stöd desto mer ökade patienternas livskvalité. Diskussion: Diskussionen är uppdelad i två delar. Metoddiskussionen innehåller styrkorna och svagheterna i författarnas genomförande av litteraturöversikten. I resultatdiskussionen valde författarna att diskutera uppkomsten av psykisk ohälsa hos patienter efter en hjärttransplantation och vikten av god information och kommunikation inom vården. Den avslutas med sjuksköterskans betydelse av att veta skillnaden mellan hälso- och sjukvården i Sverige och i andra länder. / Background: Heart transplantation has been performed since the 1960s and is today the last treatment option for severe and non-treatable heart failure. After a heart transplant, a lifelong medication is followed which reduces the risk of rejection. Patients need regular check-ups and visits to control drug dosing and to prevent side effects. The nurse has a central role in the care of heart transplant patients. It is important that the nurse has knowledge of how these patients experience their life after the heart transplant, in order to provide support and adequate person-centered care. The nurse's responsibility is to also inform the patients and their relatives about heart transplants. Aim: The aim was to describe patients experience of living with a transplanted heart. Method: The literature review was based on ten scientific articles. The articles have been analyzed and thematized with color coding. The databases CINAHL Complete and PubMed were used to search for the articles. Only qualitative articles were used in the results. Results: The result was presented in four themes. These four themes were Life after a heart transplant meant altered physical abilities, Life with a new heart meant mixed emotions, Life after heart transplant was affected by the donor and A life with a new heart meant a need for support. The result showed that patients' everyday lives had been affected both physically and mentally in conjunction with the heart transplant. The patients expressed this with different conflicting feelings, both positive and negative. The need of support from the family, care team and faith were of great importance in patients' adaptation to the new life situation. The better the support, the more the patients' quality of life increased. Discussion: The discussion is divided into two parts. The method discussion contains the strengths and weaknesses of the authors' implementation of the literature review. In the results discussion, the authors chose to discuss the onset of mental illness in patients following a heart transplant and the importance of good information and communication in health care. It concludes with the nurse's importance of knowing the difference between health care in Sweden and in other countries.

Utan ett hjärta kan inte livet fortskrida. Ibland händer det att enda utvägen för att överleva är att genomgå en hjärttransplantation. Kan en hjärttransplantation genomföras utan psykisk påverkan och hur finner mottagarna tillbaka till det liv de hade innan hjärtsjukdomen. Syftet med denna litteraturstudie var att belysa hjärttransplanterade individers psykologiska upplevelser efter en hjärttransplantation. Frågeställningarna var: Hur beskriver mottagaren som genomgått en hjärttransplantation upplevelsen av att ha en annan människas hjärta? Hur beskriver mottagaren sin strategi för att hitta tillbaka till det liv han/hon hade innan hjärttransplantationen? Hur beskriver mottagaren upplevelsen över att de fick leva på grund av någon annans död. Genom systematisk litteraturgranskning har nio vetenskapliga artiklar valts ut som kritiskt granskats enligt Carlsson och Eiman (2003) och sedan analyserats och bearbetats. I resultatet redovisas fyra teman som har identifierats: skuldkänslor gentemot donatorn och dennes familj, tacksamhet för en andra chans, coping för att hantera känslor och återgå till det dagliga livet, attityder mot det nya hjärtat och donatorn. Studien visar att det finns psykologiska aspekter såsom förnekelse och fantasier som sjuksköterskan bör ha i åtanke. / Without a heart life cannot continue. Sometimes undergoing heart transplantation is the only way to survive. Can a heart transplantation be done without psychological influence and how does the receiver find the way back to life as it was before the heart disease. The aim of this literature study was to illuminate heart transplantated individual’s psychological experiences after heart transplantation. The research questions were: How does the receiver who went through heart transplantation describe the experience of having another person’s heart? How does the receiver describe ones strategy to find the way back to the life he/she had before the heart transplantation? How does the receiver describe the experience that they live because of somebody else’s death? Through systematic literature review nine scholarly articles have been chosen and critically examined according to Carlsson and Eiman (2003) then analysed and processed. Four themes were identified and are presented under findings: feelings of guilt towards the donor and his/her family, gratitude for a second chance, coping to handle feelings and returning to daily life, attitudes towards the new heart and the donor. This study shows various psychological aspects such as denial and fantasies, which nurses should consider.

Background: The aim of this cross-sectional study was the assessment of dental behaviour and oral health condition of heart transplant recipients (HTx) in comparison to patients with heart insufficiency (HI). Methods: Patients attending the Department for Cardiac Surgery, Leipzig Heart Center, Germany were recruited. Standardized questionnaires regarding dental behaviour and periodontal complaints were applied. A dental (decayed-, missing- and filled-teeth index) and periodontal examination (periodontal probing depth (PPD) and clinical attachment loss (CAL)) was performed. Based on the oral findings, dental and periodontal treatment need was determined. Statistics: T-test, Mann-Whitney U test, Chi-square test, and Fisher-test (p < 0.05). Results: A total of 201 patients (HTx: 112, HI: 89) were included. HTx patients were significantly more often allocated to dentists (p < 0.01). Furthermore, the HTx patients rated feeling informed appropriately about oral health more often (p < 0.01). HTx patients used interdental cleaning (p < 0.01) and mouth rinse (p = 0.02) more often than HI patients. No differences between groups were present regarding dental status and periodontitis severity (p > 0.05). Periodontal treatment need was high, showing prevalence of 79.5% (HTx) and 87.6% (HI, p = 0.14), respectively. Conclusions: Both groups show insufficient oral behaviour and a high need for periodontal treatment. Special care programs for HTx candidates and recipients appear recommendable.

Cardiac transplantation is governed by complex immunological mechanisms contributing to different types of allograft rejection. Early non-specific graft failure and chronic rejection (cardiac allograft vasculopathy) represent the main limitations for the recipients’ short- and long-term survival respectively. To date, the pathogenesis of both rejection types remains ill-defined. However, it is believed that they are related to an immunologically mediated potent inflammatory process, occurring whether early after transplantation (acute), or lasting for the lifetime of the graft (chronic).<p> <p>The initiating mechanisms of chronic rejection in solid organ transplantation remain ill-defined. Emerging evidence sustains that graft vasculopathy is primarily driven by alloreactive CD4+ T lymphocytes sensitized by the indirect pathway of allorecognition. To date, whereas the nature of APCs involved in this particular pathway has yet to be identified, it appears challenging to speculate that recipient-derived endothelial cells (ECs) repopulating the graft may represent the main cell targets recognized by indirectly primed alloreactive CD4+ T cells to mediate the rejection of cardiac transplants. In the first part of this thesis, we specifically studied the indirect pathway of allorecognition with a transgenic mice (Marilyn mice) model that expresses a T cell receptor (TCR) transgene which recognizes the male antigen H-Y in an I-Ab-restricted fashion. Our results provide evidence that graft endothelium replacement by recipient-type cells expressing MHC Class II molecules is required for the chronic rejection of vascularized cardiac transplants mediated by indirect pathway alloreactive CD4+ T cells.<p><p>The purpose of the second part of the thesis was to investigate the potential implication of interleukin-22 (IL-22), an early phase secreted proinflammatory cytokine of the IL-10 family, in the acute rejection of cardiac allografts. IL-22 was recently described as an effector key modulator of the inflammatory process produced mainly by differentiated CD4+ T cells of the Th17 lineage. As being closely related to IL-10 and IL-17, both involved in the rejection process of vascularized heart allografts, we attempted to determine the precise role of IL-22 in this process. Experiments were conducted with a recently developed murine model deficient for the IL-22 gene (IL-22KO). The results of the second part of the thesis show that IL-22 is not an effector cytokine in cardiac allograft rejection. In contrast, as being early expressed into the allograft, likely IL-22 plays a protective role in the inflammation leading to acute cardiac rejection, probably depending on a neutrophil-related mechanism. <p><p><p>In conjunction with current understanding of inflammatory and antigen-specific events in allografts, overall, our results provide new insights into the mechanisms of chronic and acute cardiac rejection, thus prompting to further interrogations and appealing novel therapeutic strategies. Pharmacologic manipulation of endothelium is challenging. Given their capacity to sense and rapidly respond to the local environment, ECs are the ideal targets for rapid systemic delivery of therapeutic agents. Combination therapy is required to reduce inflammatory reaction and endothelial activation, to modulate endothelial dysfunction and promote endothelial survival. Also, given that IL-22 may alleviate tissue destruction during inflammatory responses, therapies that enhance its production and protective action in the transplanted organs seem attractive to specifically affect tissue responses, without exerting direct effects on the immune response.<p><p><p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished