Pre- and posttransplant management of solid organ transplant recipients: risk-adjusted follow-up

Solid organ transplant recipients (SOTR) have an increased risk of skin cancer due to their long-term immunosuppressive state. As the number of these patients is increasing, as well as their life expectancy, it is important to discuss the screening and management of skin cancer in this group of patients. The role of the dermatologist, in collaboration with the transplant team, is important both before transplantation, where patients are screened for skin lesions and the individual risk for skin cancer development is assessed, and after transplantation. Posttransplant management consists of regular dermatological consultations (the frequency depends on different factors discussed below), where early skin cancer screening and management, as well as patient education on sun protective behavior is taught and enforced. Indeed, SOTR are very sensitive to sun damage due to their immunosuppressive state, leading to cumulative sun damage which results in field cancerization with numerous lesions such as in situ squamous cell carcinoma, actinic keratosis and Bowen's disease. These lesions should be recognized and treated as early as possible. Therapeutic options discussed will involve topical therapy, surgical management, adjustment of the patient's immunosuppressive therapy (i.e. reduction of immunosuppression and/or switch to mammalian target of rapamycin inhibitors) and chemoprevention with the retinoid acitretin, which reduces the recurrence rate of squamous cell carcinoma. The dermatological follow-up of SOTR should be integrated into the comprehensive posttransplant care.

Apparent diffusion coefficient in the aging mouse brain: a magnetic resonance imaging study

Novel magnetic resonance imaging sequences have and still continue to play an increasing role in neuroimaging and neuroscience. Among these techniques, diffusion-weighted imaging (DWI) has revolutionized the diagnosis and management of diseases such as stroke, neoplastic disease and inflammation. However, the effects of aging on diffusion are yet to be determined. To establish reference values for future experimental mouse studies we tested the hypothesis that absolute apparent diffusion coefficients (ADC) of the normal brain change with age. A total of 41 healthy mice were examined by T2-weighted imaging and DWI. For each animal ADC frequency histograms (i) of the whole brain were calculated on a voxel-by-voxel basis and region-of-interest (ROI) measurements (ii) performed and related to the animals' age. The mean entire brain ADC of mice <3 months was 0.715(+/-0.016) x 10(-3) mm2/s, no significant difference to mice aged 4 to 5 months (0.736(+/-0.040) x 10(-3) mm2/s) or animals older than 9 months 0.736(+/-0.020) x 10(-3) mm2/s. Mean whole brain ADCs showed a trend towards lower values with aging but both methods (i + ii) did not reveal a significant correlation with age. ROI measurements in predefined areas: 0.723(+/-0.057) x 10(-3) mm2/s in the parietal lobe, 0.659(+/-0.037) x 10(-3) mm2/s in the striatum and 0.679(+/-0.056) x 10(-3) mm2/s in the temporal lobe. With advancing age, we observed minimal diffusion changes in the whole mouse brain as well as in three ROIs by determination of ADCs. According to our data ADCs remain nearly constant during the aging process of the brain with a small but statistically non-significant trend towards a decreased diffusion in older animals.

DESIGN AND SYNTHESIS OF NOVEL SYNTHETIC ANTIOXIDANTS FOR THE TREATMENT OF OXIDATIVE STRESS RELATED DISEASES

Free radicals play an important role in many physiological processes that occur in the human body such as cellular defense responses to infectious agents and a variety of cellular signaling pathways. While at low concentrations free radicals are involved in many significant metabolic reactions, high levels of free radicals can have deleterious effects on biomolecules like proteins, lipids, and DNA. Many physiological disorders such as diabetes, ageing, neurodegenerative diseases, and ischemia-reperfusion (I/R) injury are associated with oxidative stress.1 In particular, the deleterious effects caused by I/R injury developed during organ transplantation, cardiac infarct, and stroke have become the main cause of death in the United States and Europe.1,2 In this context, we synthesized and characterized a series of novel indole-amino acid conjugates as potential antioxidants for I/R injury. The synthesis of indole-phenol conjugate compounds is also discussed. Phenolic derivatives such as caffeic acid, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), resveratrol, and its analogues are known for their significant antioxidative properties. A series of resveratrol analogues have been designed and synthesized as potential antioxidants. The radical scavenging mechanisms for potential antioxidants and assays for the in vitro evaluation of antioxidant activities are also discussed.

ABO blood group incompatible haematopoietic stem cell transplantation and xenograft rejection

The current organ shortage in transplantation medicine stimulates the exploration of new strategies to expand the donor pool including the utilisation of living donors, ABO-incompatible grafts, and xenotransplantation. Preformed natural antibodies (Ab) such as anti-Gal or anti-A/B Ab mediate hyperacute graft rejection and thus represent a major hurdle to the employment of such strategies. In contrast to solid organ transplantation (SOT), ABO blood group incompatibilities are of minor importance in haematopoietic stem cell transplantation (HSCT). Thus, ABO incompatible HSCT may serve as an in vivo model to study carbohydrate antigen (Ag)-mismatched transplantations such as ABO-incompatible SOT or the effect of preformed Ab against Gal in xenotransplantation. This mini-review summarises our clinical and experimental studies performed with the support of the Swiss National Science Foundation program on Implants and Transplants (NFP-46). Part 1 describes data on the clinical outcome of ABO-incompatible HSCT, in particular the incidence of several immunohaematological complications, acute graft-versus-host-disease (GvHD), and the overall survival. Part 2 summarises the measurements of anti-A/B Ab in healthy blood donors and ABO-incompatible HSCT using a novel flow cytometry based method and the potential mechanisms responsible for the loss of anti-A/B Ab observed following minor ABO-incompatible HSCT, ie the occurrence of humoral tolerance. Part 3 analyses the potential of eliminating Gal expression as well as specific complement inhibitors such as dextran sulfate and synthetic tyrosine analogues to protect porcine endothelial cells from xenoreactive Ab-mediated damage in vitro and in a hamster-to-rat heart transplantation model. In conclusion, due to similarities of the immunological hurdles of ABO incompatible transplantations and xenotransplantation, the knowledge obtained from both fields might lead to new strategies to overcome humoral rejection in transplantation.

Taxonomy development and knowledge representation of nurses' personal cognitive artifacts.

Nurses prepare knowledge representations, or summaries of patient clinical data, each shift. These knowledge representations serve multiple purposes, including support of working memory, workload organization and prioritization, critical thinking, and reflection. This summary is integral to internal knowledge representations, working memory, and decision-making. Study of this nurse knowledge representation resulted in development of a taxonomy of knowledge representations necessary to nursing practice.This paper describes the methods used to elicit the knowledge representations and structures necessary for the work of clinical nurses, described the development of a taxonomy of this knowledge representation, and discusses translation of this methodology to the cognitive artifacts of other disciplines. Understanding the development and purpose of practitioner's knowledge representations provides important direction to informaticists seeking to create information technology alternatives. The outcome of this paper is to suggest a process template for transition of cognitive artifacts to an information system.

Overview of dermatologic problems following liver transplantation

Liver transplantation recipients, like other solid organ transplantation recipients, have an increased risk of dermatologic problems due to their long-term immunosuppression and benefit from pre-and post-transplantation screenings, and management by a dermatologist and dermatologic care should be integrated into the comprehensive, multidisciplinary care of liver transplantation recipients [1,2]. Cutaneous findings include aesthetic alterations, infections, precancerous lesions, and malignancies. The severity of skin alterations ranges from benign, unpleasant changes to life-threatening conditions [3-5]. In addition to skin cancer diagnosis and management, visits with a dermatologist serve to educate and improve the patient's sun-protection behavior. Among all solid organ transplantations, liver transplantation requires the least amount of immunosuppression, sometimes even permitting its complete cessation [6]. As a result, patients who have undergone liver transplantation tend to have fewer dermatologic complications compared with other solid organ transplantation recipients [7]. However, due to the large volume of the liver, patients undergoing liver transplantation receive more donor lymphocytes than kidney, heart, or lung transplantation recipients. Because of the immunosuppression, the transplanted lymphocytes proliferate and rarely trigger graft-versus-host-disease [8,9]. This topic will provide an overview of dermatologic disorders that may be seen following liver transplantation. A detailed discussion of skin cancer following solid organ transplantation and the general management of patients following liver transplantation are discussed separately. (See "Development of malignancy following solid organ transplantation" and "Management of skin cancer in solid organ transplant recipients" and "Long-term management of adult liver transplant recipients".)

Risk Behavior and Reciprocity of Organ Donation Attitudes in Young Men

Background Lack of donor organs remains a major obstacle in organ transplantation. Our aim was to evaluate (1) the association between engaging in high-risk recreational activities and attitudes toward organ donation and (2) the degree of reciprocity between organ acceptance and donation willingness in young men. Methods A 17-item, close-ended survey was offered to male conscripts ages 18 to 26 years in all Swiss military conscription centers. Predictors of organ donation attitudes were assessed in bivariate analyses and multiple logistic regression. Reciprocity of the intentions to accept and to donate organs was assessed by means of donor card status. Results In 1559 responses analyzed, neither motorcycling nor practicing extreme sports reached significant association with donor card holder status. Family communication about organ donation, student, or academic profession and living in a Latin linguistic region were predictors of positive organ donation attitudes, whereas residence in a German-speaking region and practicing any religion predicted reluctance. Significantly more respondents were willing to accept than to donate organs, especially among those without family communication concerning organ donation. Conclusions For the first time, it was shown that high-risk recreational activities do not influence organ donation attitudes. Second, a considerable discrepancy in organ donation reciprocity was identified. We propose that increasing this reciprocity could eventually increase organ donation rates.

Efeitos da Implementação da Sistematização da Assistência de Enfermagem nos Enfermeiros de uma Instituição de Saúde Pública

O presente estudo teve como objetivos investigar a opinião do enfermeiro sobre a Sistematização da Assistência de Enfermagem, verificar os efeitos da Sistematização da Assistência de Enfermagem na organização do trabalho do enfermeiro e identificar se a Implementação da Sistematização da Assistência de Enfermagem causa sofrimento psíquico nesses profissionais. Trata-se de uma pesquisa qualitativa, realizada com 22 enfermeiros que atuam em uma instituição pública de saúde do grande ABCD, no Estado de São Paulo. Foram utilizadas entrevistas semi-estruturadas, por meio de gravação dos depoimentos. A análise dos dados foi realizada buscando apreender os conteúdos representacionais sobre os efeitos da Implementação da Sistematização da Assistência de Enfermagem nos Enfermeiros. As categorias de análise sobre a influência da SAE nos sujeitos foram: a)conhecimento sobre a SAE: tem conhecimento e tem pouco conhecimento; b)opinião sobre a SAE: favorável e parcialmente favorável; c)desenvolvimento da SAE no contexto do trabalho: ocorre parcialmente e não ocorre; d)influência da Implementação da SAE no desempenho das tarefas: afeta e não afeta; e)ocorrência de sofrimento psíquico na Implementação da SAE : há e não há expressões diretas de sofrimento psíquico. Os dados revelaram que os efeitos da Implementação da Sistematização da Assistência de Enfermagem nos Enfermeiros causam sofrimento psíquico, resultantes das condições de trabalho inadequadas para promover a Sistematização da Assistência de Enfermagem.

Efeitos da Implementação da Sistematização da Assistência de Enfermagem nos Enfermeiros de uma Instituição de Saúde Pública

O presente estudo teve como objetivos investigar a opinião do enfermeiro sobre a Sistematização da Assistência de Enfermagem, verificar os efeitos da Sistematização da Assistência de Enfermagem na organização do trabalho do enfermeiro e identificar se a Implementação da Sistematização da Assistência de Enfermagem causa sofrimento psíquico nesses profissionais. Trata-se de uma pesquisa qualitativa, realizada com 22 enfermeiros que atuam em uma instituição pública de saúde do grande ABCD, no Estado de São Paulo. Foram utilizadas entrevistas semi-estruturadas, por meio de gravação dos depoimentos. A análise dos dados foi realizada buscando apreender os conteúdos representacionais sobre os efeitos da Implementação da Sistematização da Assistência de Enfermagem nos Enfermeiros. As categorias de análise sobre a influência da SAE nos sujeitos foram: a)conhecimento sobre a SAE: tem conhecimento e tem pouco conhecimento; b)opinião sobre a SAE: favorável e parcialmente favorável; c)desenvolvimento da SAE no contexto do trabalho: ocorre parcialmente e não ocorre; d)influência da Implementação da SAE no desempenho das tarefas: afeta e não afeta; e)ocorrência de sofrimento psíquico na Implementação da SAE : há e não há expressões diretas de sofrimento psíquico. Os dados revelaram que os efeitos da Implementação da Sistematização da Assistência de Enfermagem nos Enfermeiros causam sofrimento psíquico, resultantes das condições de trabalho inadequadas para promover a Sistematização da Assistência de Enfermagem.

Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver

The ability to identify, isolate, and transplant progenitor cells from solid tissues would greatly facilitate the treatment of diseases currently requiring whole organ transplantation. In this study, cell fractions enriched in candidate epithelial progenitor cells from the rat pancreas were isolated and transplanted into the liver of an inbred strain of Fischer rats. Using a dipeptidyl dipeptidase IV genetic marker system to follow the fate of transplanted cells in conjunction with albumin gene expression, we provide conclusive evidence that, after transplantation to the liver, epithelial progenitor cells from the pancreas differentiate into hepatocytes, express liver-specific proteins, and become fully integrated into the liver parenchymal structure. These studies demonstrate the presence of multipotent progenitor cells in the adult pancreas and establish a role for the liver microenvironment in the terminal differentiation of epithelial cells of foregut origin. They further suggest that such progenitor cells might be useful in studies of organ repopulation following acute or chronic liver injury.

Aplicación práctica de los modelos de Mercer y Beck en las especialidades de enfermería

El vínculo afectivo es la atracción que un individuo siente por otro. La conducta de apego busca la unión emocional y seguridad del bebé hacia su madre. Distintas especialidades de enfermería indican la importancia de trabajar el vínculo afectivo, las relaciones familiares y utilizar el proceso enfermero partiendo de modelos conceptuales. Los modelos conceptuales de Mercer y Beck estudian factores a considerar en la formación y desarrollo de vínculos afectivos entre madres e hijos. Este estudio pretende desarrollar conocimientos, habilidades y actitudes que permitan una atención óptima al bebé y su familia. Analizando los elementos comunes y diferenciadores de ambos modelos y justificando la necesidad de prestar especial atención a la formación y mantenimiento del vínculo maternofilial desde la perspectiva de las diferentes especialidades de enfermería, se utiliza el proceso enfermero para la detección y resolución de problemas que afecten al vínculo afectivo y a las relaciones familiares.

Sistematização da assistencia de enfermagem numa UTI geral: um contributo para a sua implementação

Enquadramento: A Sistematização da Assistência de Enfermagem (SAE) contribui de forma significativa para a qualidade da assistência prestada ao cliente e, as ações de enfermagem, são delineadas e individualizadas, transmitindo maior segurança, estabilidade e veracidade para o cliente e toda a equipe envolvida neste processo. Objetivo: O estudo teve como objetivo identificar os conhecimentos da equipe de enfermagem sobre a SAE e a sua participação nesse processo, revestindo-se em benefícios por sensibilizar a equipe de enfermagem da UTI Geral para a implementação de um modelo de SAE composto pelas etapas do PE: Histórico, Diagnóstico, Prescrição e Evolução de Enfermagem. Metodologia: Trata-se de um estudo descritivo de abordagem quantitativa. Para a colheita de dados utilizamos um questionário elaborado para o efeito. O estudo decorreu entre o período setembro a dezembro de 2014, no Hospital Agamenon Magalhães, Recife, Brasil, numa amostra de 650 profissionais de enfermagem. Resultados: Pelos resultados do estudo verificamos que 84,4% (190) dos profissionais inquiridos demonstram ter conhecimentos sobre a SAE, 97,8% (220) concordam sobre a sua importância no planeamento da assistência e, consequentemente, com a implementação do processo, embora 41,8% (94) não manifestem motivação para trabalhar com a mesma. Conclusão: O estudo da SAE e sua implementação é de suma importância desenvolvendo competências, treinamentos e motivações para que o cuidado possa ser de qualidade. Também há necessidade de estimular e preparar os profissionais de enfermagem para atuarem de forma sistematizada junto do paciente, através do processo de enfermagem, numa relação interpessoal e marcada pela competência científica, técnica e ética. Palavras-chave: unidade de terapia intensiva; teorias de enfermagem; sistematização da assistência de enfermagem; processo de enfermagem.

Toward better outcomes with tacrolimus therapy: Population pharmacokinetics and individualized dosage prediction in adult liver transplantation

Patient outcomes in transplantation would improve if dosing of immunosuppressive agents was individualized. The aim of this study is to develop a population pharmacokinetic model of tacrolimus in adult liver transplant recipients and test this model in individualizing therapy. Population analysis was performed on data from 68 patients. Estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F) using the nonlinear mixed effects model program (NONMEM). Factors screened for influence on these parameters were weight, age, sex, transplant type, biliary reconstructive procedure, postoperative day, days of therapy, liver function test results, creatinine clearance, hematocrit, corticosteroid dose, and interacting drugs. The predictive performance of the developed model was evaluated through Bayesian forecasting in an independent cohort of 36 patients. No linear correlation existed between tacrolimus dosage and trough concentration (r(2) = 0.005). Mean individual Bayesian estimates for CL/F and V/F were 26.5 8.2 (SD) L/hr and 399 +/- 185 L, respectively. CL/F was greater in patients with normal liver function. V/F increased with patient weight. CL/F decreased with increasing hematocrit. Based on the derived model, a 70-kg patient with an aspartate aminotransferase (AST) level less than 70 U/L would require a tacrolimus dose of 4.7 mg twice daily to achieve a steady-state trough concentration of 10 ng/mL. A 50-kg patient with an AST level greater than 70 U/L would require a dose of 2.6 mg. Marked interindividual variability (43% to 93%) and residual random error (3.3 ng/mL) were observed. Predictions made using the final model were reasonably nonbiased (0.56 ng/mL), but imprecise (4.8 ng/mL). Pharmacokinetic information obtained will assist in tacrolimus dosing; however, further investigation into reasons for the pharmacokinetic variability of tacrolimus is required.

Pharmacokinetic considerations relating to tacrolimus dosing in the elderly

Relaxation of the upper age limits for solid organ transplantation coupled with improvements in post-transplant survival have resulted in greater numbers of elderly patients receiving immunosuppressant drugs such as tacrolimus. Tacrolimus is a potent agent with a narrow therapeutic window and large inter- and intraindividual pharmacokinetic variability. Numerous physiological changes occur with aging that could potentially affect the pharmacokinetics of tacrolimus and, hence, patient dosage requirements. Tacrolimus is primarily metabolised by cytochrome P450 (CYP) 3A enzymes in the gut wall and liver. It is also a substrate for P-glycoprotein, which counter-transports diffused tacrolimus out of intestinal cells and back into the gut lumen. Age-associated alterations in CYP3A and P-glycoprotein expression and/or activity, along with liver mass and body composition changes, would be expected to affect the pharmacokinetics of tacrolimus in the elderly. However, interindividual variation in these processes may mask any changes caused by aging. More investigation is needed into the impact aging has on CYP and P-glycoprotein activity and expression. No single-dose, intense blood-sampling study has specifically compared the pharmacokinetics of tacrolimus across different patient age groups. However, five population pharmacokinetic studies, one in kidney, one in bone marrow and three in liver transplant recipients, have investigated age as a co-variate. None found a significant influence for age on tacrolimus bioavailability, volume of distribution or clearance. The number of elderly patients included in each study, however, was not documented and may have been only small. It is likely that inter- and intraindividual pharmacokinetic variability associated with tacrolimus increase in elderly populations. In addition to pharmacokinetic differences, donor organ viability, multiple co-morbidity, polypharmacy and immunological changes need to be considered when using tacrolimus in the elderly. Aging is associated with decreased immunoresponsiveness, a slower body repair process and increased drug adverse effects. Elderly liver and kidney transplant recipients are more likely to develop new-onset diabetes mellitus than younger patients. Elderly transplant recipients exhibit higher mortality from infectious and cardiovascular causes than younger patients but may be less likely to develop acute rejection. Elderly kidney recipients have a higher potential for chronic allograft nephropathy, and a single rejection episode can be more devastating. There is a paucity of information on optimal tacrolimus dosage and target trough concentration in the elderly. The therapeutic window for tacrolimus concentrations may be narrower. Further integrated pharmacokinetic-pharmaco-dynamic studies of tacrolimus are required. It would appear reasonable, based on current knowledge, to commence tacrolimus at similar doses as those used in younger patients. Maintenance dose requirements over the longer term may be lower in the elderly, but the increased variability in kinetics and the variety of factors that impact on dosage suggest that patient care needs to be based around more frequent monitoring in this age group.