Research on age differences in heart transplant patients has focused primarily on medical outcomes, with mixed findings regarding mortality and morbidity rates and limited research regarding age differences in psychosocial and quality of life outcomes. To gain a more complete understanding of psychosocial adjustment after heart transplant, this study examined age differences in: satisfaction with quality of life, satisfaction with social support, depressive symptoms, negative affect, symptom distress, stress related to heart transplant, overall health functioning, coping strategies, and aspects of adherence. Results indicate that older patients, compared to younger patients, report better adjustment and quality of life across numerous outcomes 5-10 years after heart transplant. These findings are consistent with previous literature examining age differences in developmental changes with emotion regulation and coping. This study hopes to contribute to the discussion of age and heart transplant, highlighting the importance of considering quality of life in addition to medical outcomes.

ABSTRACT MOLECULAR MECHANISMS AND GENE SIGNATURES INVOVLED IN CALCINEURIN INHIBITOR NEPHROTOXICITY IN KIDNEY ALLOGRAFT By Huong Le Diem Nguyen, M.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Physiology at Virginia Commonwealth University. Virginia Commonwealth University, 2011. Major Director: Valeria Mas, Ph.D. Associate Professor, Department of Surgery and Pathology Director of Molecular Transplant Research Laboratory, Division of Transplant Calcineurin inhibitors (CNI), cyclosporin A and tacrolimus, are potent immunosuppressive agents but induce toxicities causing damages and graft dysfunction, and have been suggested to contribute to late-term loss of graft in kidney transplant recipients. Even though insights on mechanism of CNI nephrotoxicity have been uncovered, prevention and treatment of these toxicities remain a major challenge in the clinical administration of CNI due to low dose-toxicity correlation, difficulty in establishing a differential patho-histological diagnosis, and varying individual susceptibility. We hypothesize that CNI nephrotoxicity follows distinct disease pathways and is characterized by significant gene signatures that differentiate it from other conditions such as acute rejection and chronic allograft dysfunction. Moreover, we postulate that CNI-induced toxicity profiles contribute to the IF/TA signatures. Microarray analysis and gene annotation were done on the study database included of tissues diagnosed with CNI nephrotoxicity (n = 9), interstitial fibrosis/tubular atrophy (IF/TA, n=10), and normal allografts (NA, n = 8). All samples were histologically classified based on the revised Banff ‘07 criteria for renal allograft pathology. Top-scored biological networks in CNI tissues were related to metabolic disease, cellular development, renal necrosis, apoptosis cell-death, immunological disease, inflammatory disease, and many others. Canonical pathway analysis emphasized oxidative stress response mediated by NRF2 and various cell-death signaling pathways including 14-3-3 signaling pathway, p53 signaling pathway, and TGF-β signaling pathway. Profiling of differentially expressed genes was done based on their statistical significance and biological relevance to the unique pathology of CNI nephrotoxicity. Among these, three genes RGS1, CXCR4, and TGIF1 were further quantitatively evaluated using real time-PCR. Between CNI group and normal allograft, t-test results showed only RGS1 gene expression level was statistically significant. Between IF/TA group in normal allograft, both RGS1 and CXCR4 showed statistical significance. The calculated relative fold changes revealed an up-regulated pattern of RGS1 and CXCR4 expression in association with pathological groups (CNI and IF/TA). We did not, however, find any association between the expression of TGIF1 in either CNI group or IF/TA group.

End stage renal disease (ESRD) is a growing epidemic impacting the United States. While the optimal treatment for ESRD is renal replacement, barriers exist making this treatment difficult and sometimes impossible for patients to pursue. One potential solution to existing barriers is to encourage patients to actively seek living donors. This is an inherently communicative and social process. The Theory of Motivated Information Management (TMIM) offers a framework for understanding factors that contribute to patients’ conversations about transplantation with their social networks. It is also possible that Patient Empowerment can add to this model, and inform future patient education. Specific variables related to the TMIM and Patient Empowerment are analyzed in bivariate and logistic regression analyses. Variables that were significant in bivariate analysis did not rise to the level of significance when included in a full logistic regression analysis. Study results and outcomes suggest that further research is warranted.

No description available.

O osso alógeno fresco-congelado (FFBA, do inglês fresh-frozen bone allograft) é uma alternativa para os procedimentos cirúrgicos de enxerto ósseo, principalmente na preparação do rebordo alveolar para a instalação de implantes osseointegráveis. No entanto, existem alguns paradigmas que envolvem a relação entre resposta do sistema imunológico à aloantígenos presentes no enxerto e o seu comportamento clínico. Procurando entender essa relação, o FFBA foi avaliado como enxerto para preservar o rebordo alveolar pós-extração. Os resultados mostraram que embora tenha ocorrido uma redução estatisticamente significante na altura, espessura e volume do rebordo entre a avaliação inicial e final, essa redução não foi clinicamente significante, permitindo a instalação de implantes osseointegráveis. Em adição, as análises histológicas sugerem um bom comportamento do enxerto, com ausência de reação do tipo corpo estranho e formação de novo osso em todos os sítios analisados. Ao analisar o comportamento da resposta imune, os resultados mostraram que a injeção intradérmica de aloantígenos presentes no FFBA, não induziu uma reação de hipersensibilidade tardia nos pacientes após 4 meses do enxerto. Além disso, os monócitos do sangue periférico (PBMCs) dos pacientes não proliferaram frente aos aloantígenos in vitro. No entanto, os dados também demonstraram que os aloantígenos aumentam a produção de IL-2 e IFN-, mas não alteram a produção de IL-4 e IL-10, por PBMCs dos pacientes. Ao avaliar a relação entre a produção dessas citocinas e o comportamento clínico do enxerto, os dados mostram que existe uma correlação estatisticamente significante entre a produção de IL-2 in vitro e a redução (em %) da altura do rebordo alveolar, embora essa redução não tenha sido clinicamente significante. De fato, a presença de aloantígenos no FFBA não é suficiente para sua contraindicação como material de enxertia. / The fresh-frozen bone allograft (FFBA) is an alternative to surgical procedures of bone grafts, mainly in the preservation of alveolar ridge prior the installation of osseointegrated implants. However there are paradigms that surround the relation between immune response to alloantigens present inside the graft and the clinical response of the graft. An attempt to understand this relationship, the FFBA was evaluated as a graft to preserve the alveolar ridge post-extraction. The results show a statistically significant reduction in height, thickness and volume of the ridge between the initial and final examination, however this reduction was not clinically significant. The ridge preservation allowed implant installation and osseointegration. In addition, histologic analysis suggests a good performance of the graft with no foreign body reaction and formation of new bone at all sites. In analyzing the behavior immune response, the results showed that stimulation with alloantigens present in bone allograft induced no delayed hypersensitivity reaction in vivo. Additionally, periphery blood mononuclear cells (PBMC) from patients no proliferate in response to alloantigens in vitro. However, the data also demonstrated that the alloantigens increase IL-2 and IFN- production, but no IL-4 and IL-10 production, by PBMCs from patients. When evaluate the relation between the cytokines production and clinical parameters, the results demonstrate that there statistically significant correlation between IL-2 production in vitro and ridge height changes (%), although this clinical parameter is not clinically significant. In fact, the alloantigens in FFBA are not sufficient for its contraindications as grafting material.

En levertransplantation är ett livsförändrande ingrepp som innebär en chans till ett nytt liv för patienter med en livshotande diagnos. Ingreppet medför också stora omställningar för patienter i form av fysiska och psykiska svårigheter. Genom att få en större inblick i patienters livssituation kan sjuksköterskorna med den nyvunna kunskapen, ge en bättre anpassad vård till patienterna. Syftet med denna uppsats är att belysa patienternas upplevelser av sin livssituation efter en levertransplantation. Metoden som används är en litteratur baserad studie utifrån kvalitativa vetenskapliga artiklar, inriktat på patienters upplevelse kring levertransplantation. Åtta artiklar analyserades enligt Evans (2003) där två huvudteman samt åtta subteman kunde urskiljas. Patienterna upplevde en dramatisk förändring i sitt välbefinnande efter operationen och strävade efter att återgå till det liv de hade innan sjukdomen debuterade. Det fanns dock en ständigt överhängande rädsla för organavstötning som förde med sig ett stort lidande för patienterna. Stöd från närstående, andra patienter som delat samma erfarenhet samt vårdpersonal med erfarenhet och kunskap ansågs vara essentiellt för tillfrisknandet. Vårdgivarens kännedom om patienternas upplevelse i samband med en levertransplantation är av yttersta betydelse för patienterna. Kännedomen om att sjuksköterskan kan relatera till vad patienterna säger och hur de mår, främjar vårdrelationen och därmed omvårdnaden. / Program: Sjuksköterskeutbildning

A medição de desempenho é estratégica para as organizações. Este estudo de caso investiga as medidas de desempenho do sistema nacional de transplantes, baseando-se na regional interior de São Paulo, focalizando uma equipe de transplante de fígado. Usa entrevistas abertas e análise de documentos para levantar evidências. Conclui que há carência de um conjunto sistemático de indicadores que auxilie a equipe a melhorar o desempenho logístico. Embora todos os membros reconheçam a importância da logística, faltam indicadores logísticos específicos para monitoramento de processos. A equipe acompanha um conjunto de indicadores de resultado como usual na área da medicina, focados no bem estar dos pacientes. Como alternativa, este trabalho analisa um conjunto de indicadores propostos por auditoria externa, notando que os indicadores propostos ainda são de resultado e não contribuem para a melhoria das funções e processos de transplante. / Performance measurement is strategic for organizations. This case study researches logistics performance measure of brazilian national transplant system, based on countryside regional of São Paulo state, focused in liver transplant team. It uses open interviews and document analysis. It finds out there is no systematic set of indicators that helps the team to improve logistics performance. Although all members recognize logistics importance, there are no specific logistic indicators for monitoring processes. A set of resulting indicators is followed up, as usual in medical area, all of them focused in welfare-state of patients. Alternatively, this work analyses a set of indicators just proposed to the organization by a external audition, realizing that the new indicators don´t contribute to function and processes improvement.

Typically, dormant seedlings are transplanted when revegetating nonirrigated disturbed lands in order to prevent transplant shock triggered by water stress. Since dormant seedlings have to be used, this limits the duration of the transplant season. It may be possible to increase this limited season by inducing acclimation responses that would increase drought tolerance. Preconditioning actively growing seedlings to water stress prior to transplanting could induce acclimation responses such as solute accumulation and/or stomatal modulation. Under greenhouse conditions, A. cana and A. intermedium seedlings were subjected to three water stress preconditioning treatments: a well watered control, one dry-down cycle, and three dry-down cycles. After conditioning, seedlings were either allowed to dry-down in their containers until leaf senescence, or were transplanted to disturbed land sites. Plant water potential components, relative water content, and leaf mortality were measured. Immediately following treatments, water relations parameters of preconditioned seedlings were not markedly different from controls in either species. At the end of the final dry-down, water stress preconditioning had not induced active or passive solute accumulation, prolonged leaf survival when exposed to lethal drought conditions, or resulted in differences in transplant survival rates under the experimental conditions of this study.

Persons with spinal cord injury (SCI) suffer life-long consequences including paralysis, loss of involuntary bodily functions, and chronic pain. A subset of SCI patients develop neuropathic pain (NP), a chronic condition resulting from damage to the spinal cord. Hyperexcitability of spinal cord sensory neurons near damaged tissue is believed to underlie SCI-related NP. Although many therapies have been employed clinically to combat SCI-NP, few give satisfactory long-term relief. Transplantation of cells that release GABA, a molecule that inhibits neuronal activity, is being explored as an alternative to current SCI-NP therapies. My experiments made progress toward preclinical modeling of GABA cell therapy for SCI-NP. First, I sought to determine whether quisqualic acid (QUIS)-induced SCI altered responses to tonic pain stimuli or altered GABAergic neural circuitry in rats. Second, I sought to determine whether a combination of genetic and trophic manipulations could promote a GABAergic phenotype in rat embryonic neural precursor cells (NPCs) in an in vitro culture system. The results revealed that QUIS-SCI rats exhibit unusually prolonged nocifensive responses to hind paw formalin injections. There was no significant difference between QUIS-SCI and sham surgery rats in c-Fos immunolabeling of spinal cord sensory neurons after formalin-induced neuronal activity. However, immunohistochemistry revealed substantial decreases in staining for markers of GABA presynaptic vesicles in injured spinal cord tissue. NPCs were enriched for a neuronal phenotype by combining withdrawal of the growth factor FGF-2 from culture media and overexpression of the transcription factor MASH1 in transfected cells. Although glial marker expression was suppressed in NPCs by these manipulations, expression of neuronal markers none the less declined through time. MASH1-overexpressing NPCs exhibited greater clonal expansion and decreased stress-induced PDI expression after FGF-2 withdrawal as compared to naïve. In light of existing data, these results suggest that the QUIS-SCI model may be useful for testing the efficacy of GABAergic NPC transplantation to reduce neuropathic pain. MASH1 overexpression and FGF-2 withdrawal could serve as a first step toward enriching GABA in NPCs for transplantation. Although the mechanism for MASH1 cytoprotection remains unclear, MASH1 may enhance survival of NPCs grafted into the spinal cord. These experiments contributed to the preclinical basis for application of therapeutic GABAergic stem cell transplantation for NP in human SCI patients.

Background: Dilated Cardiomyopathy (DCM) is the most common functional type of cardiomyopathy in children with significant morbidity and the leading indication for cardiac transplant over 5 years of age. Identification of baseline risk factors for failing medical management by etiologic grouping remain to be elucidated in a large populationbased study. The competing risk for heart death between all-cause mortality and heart transplantation is often overestimated in the literature and may obscure additional novel risk factors associated with poor clinical outcomes. Methods: The National Heart Lung and Blood Institute Pediatric Cardiomyopathy Registry collected longitudinal data from 1731 children with DCM in North America from 1990 to 2007. Composite endpoint (CEP) was the earlier occurrence of death or heart transplant. Univariate and multivariate predictors were identified from demographic and echocardiographic data (expressed as z-scores) collected within 30 days of diagnosis. A competing risk analysis was performed calculating cumulative incidence and identifying novel prognostic factors. All analyses were performed by etiologic group. Results: Multivariate Cox regression identified the highest mortality risk among children with idiopathic disease (N=1192, CEP: 41%) when diagnosed over age 6 years, and with congestive heart failure (CHF) and decreased left ventricular fractional shortening (FS). Risk factors for those with myocarditis (N=272, CEP: 26%) were older age, CHF, and increased left ventricular (LV) end-diastolic dimension (EDD); while for neuromuscular disease (N=139, CEP: 40%), it was a decreased FS and increased EDD. Only univariate predictors were identified for children with familial isolated cardiomyopathy (N=79, CEP: 44%) including: CHF, increased EDD, end-systolic dimension, or LV mass, and decreased FS or ejection fraction), while for children with inborn errors of metabolism (N=43, CEP: 33%) risk factors included: a positive family history of cardiomyopathy or genetic syndromes. The group of children with malformation syndromes (N=6, CEP: 50%) was not large enough to model. Comparison of cause-specific event rates between Kaplan-Meier and cumulative incidence demonstrated an overestimation with the former method. Competing risk multivariate regression showed similar models to those for CEP, with the following exceptions: for neuromuscular disease, an increased EDD had a larger hazard ratio for transplant than for death; for idiopathic disease, an increased EDD was associated with transplant, but not with death, and growth retardation (height-for-age zscore) was associated with death but not transplant. Conclusions: Within etiologic grouping, demographics and echocardiographic values at diagnosis have varying predictive value. Generally, the presence of symptomatic disease in the form of CHF, echocardiographic evidence of more severe DCM, and increased age were indicative of worse outcomes. These results help to validate those from conflicting studies; however, they suggest that etiology modifies the importance of particular factors. Analysis of competing risk provides an alternate interpretation of studies with composite endpoints and assists in the transfer of clinically relevant information. For children with idiopathic and neuromuscular disease, the degree of dilation had a differential effect that has gone unrecognized. The novel finding of reduced stature and its effect on mortality suggests a potential for treatment and mitigation of poor outcomes in idiopathic DCM. Both increased dilation and reduced stature could be used to improve the triage process and refer children to cardiac transplantation who otherwise might die prematurely and unnecessarily. Subsequent studies on the utility of these factors and their effect on improving survival are warranted.