Evaluación de una herramienta educativa en conocimiento de donación y trasplante de órganos y tejidos en Colombia

El trasplante de órganos es considerado uno de los avances más significativos de la medicina moderna y es un procedimiento cada vez más exitoso en términos de supervivencia de los pacientes, siendo actualmente la mejor opción de tratamiento para los pacientes con innumerables patologías. El proceso de donación es insuficiente para cubrir las necesidades de trasplante de la población, por lo tanto, se hace necesario el desarrollo de nuevas estrategias para fortalecer la experiencia y efectividad de los programas existentes. La falta de conocimiento de los profesionales de la salud, su percepción y actitud hacia temas relacionados con el proceso de donación, pueden convertirlos en facilitadores o barreras para la identificación de potenciales donantes. Por esta razón, los recursos disponibles, las actitudes hacia la donación, la legislación y conocimiento de los procesos involucrados en la donación de tejidos y órganos son críticos. Dada la influencia de los profesionales de salud se definen los objetivos de este proyecto de tesis: determinar cuál es el conocimiento y las habilidades de los profesionales de la salud encargados de los trasplantes de órganos y de tejidos en la regional 1, evaluados mediante una herramienta educativa para contribuir a mejorar un programa eficiente de Donación de Órganos y tejidos y así mismo, fijar recomendaciones en aras de aumentar las tasas de donación, con especial énfasis en la actividad hospitalaria en el país. METODOLOGIA Se realizó un estudio basado en el análisis de la evaluación de conocimientos del proceso donación- trasplante de órganos y tejidos en el personal de salud participante en la herramienta educativa llamada “Curso taller primer respondiente del potencial donante de órganos y tejidos”. Este curso incluía un formato evaluativo que fue diligenciado de manera anónima por los participantes antes y después de recibir el contenido del curso. El estudio se desarrolló en personal de la Salud de IPS pertenecientes a la Regional I, de la Red Nacional de donación y trasplantes de órganos y tejidos. Con el fin de evidenciar si existen diferencias en el conocimiento de los participantes del curso antes y después de asistir al mismo, se utilizó la prueba de McNemar (p< 0.05). RESULTADOS Entre julio del 2011 y junio del 2012, se realizó el “Curso taller primer respondiente del potencial donante de órganos y tejidos” y se obtuvieron 303 encuestados incluidos médicos, enfermeras y auxiliares de enfermería. Al inicio del curso las respuestas acertadas con relación a legislación, selección del donante, muerte encefálica y mantenimiento del donante estuvieron alrededor del 50%. No fue posible detectar la profesión que pudiese generar riesgo en la detección del donante y los procesos asociados. Posterior al curso, el 72% de las preguntas se respondieron de manera correcta, lo que representa un incremento estadísticamente significativo. Este cambio evidenció significancia estadística al usar la prueba de McNemar y arrojar un valor de p=0.00. .DISCUSIÓN El personal de salud participante en el curso taller proveniente de unidades involucradas como generadoras de donantes muestra un déficit de conocimientos del proceso donación trasplantes lo que puede convertirlos en limitantes para dicho proceso

Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.

Mediastinitis post revascularización miocárdica: impacto del cambio de profilaxis antibiótica en la fundación Cardioinfantil 2012 - 2013

INTRODUCCIÓN. La mediastinitis posterior a cirugía de revascularización miocárdica es una infección infrecuente, pero potencialmente fatal. En la Fundación Cardioinfantil se ha observado una tendencia al incremento de la misma en los últimos años, obligando a un cambio en las medidas de profilaxis antimicrobiana, pasando de cefalosporinas a vancomicina – gentamicina, sin embargo no se conoce aún el impacto de estas medidas. OBJETIVO: Determinar si el cambio de la profilaxis antibiótica en pacientes sometidos a revascularización miocárdica influye en una disminución de la incidencia de mediastinitis durante los años 2012 – 2013. METODOLOGÍA: Estudio de cohortes retrospectivo, evaluando la incidencia de mediastinitis post revascularización miocárdica, en pacientes expuestos a 2 diferentes tipos de profilaxis antimicrobiana (cefalosporinas vs vancomicina-gentamicina). Se describieron los patrones de susceptibilidad y resistencia de los patógenos encontrados en mediastinitis y la mortalidad de esta patología. RESULTADOS: Los patógenos más frecuentemente aislados en la mediastinitis fueron Staphylococcus aureus y Klebsiella pneumoniae, en la mayoría monomicrobiano. Se encontraron patógenos con perfiles de resistencia como betalactamasas de espectro extendido en Gram negativos y resistencia a la meticilina en cocos Gram positivos. El RR de mediastinitis del grupo expuesto a vancomicina-gentamicina respecto al grupo de cefalosporinas fue de 0,9 con IC 95% 0,28 – 3,28. CONCLUSIÓN: la epidemiologia microbiana de la mediastinitis no difiere de la reportada en otras series. La profilaxis antimicrobiana con vancomicina - gentamicina en pacientes sometidos a revascularización miocárdica, no redujo la incidencia de mediastinitis. Se propone regresar a la terapia de profilaxis con cefalosporinas.

Supervivencia en pacientes con trasplante hepático realizado en la Fundación Cardioinfantil entre 2005 y 2013

Introducción: El trasplante hepático es la terapia de elección para los pacientes con enfermedad hepática terminal, logrando mejorar su expectativa y calidad de vida, de acuerdo a estudios realizados en otros países. En la Fundación Cardioinfantil – Instituto de Cardiología (FCI-IC) se han realizado 332 trasplantes hepáticos hasta el 2014, pero no se conoce la supervivencia y los factores pronósticos propios de los pacientes intervenidos. Objetivo Principal: Estimar la supervivencia a 1, 3 y 5 años e identificar los principales factores pronósticos de los pacientes a quienes se les realizó trasplante hepático en el periodo 2005-2013 en la FCI-IC. Método: Estudio observacional y retrospectivo, basado en revisión de historias clínicas de los pacientes adultos a quienes se les realizó trasplante hepático en el periodo 2005-2013 en la FCI-IC. Resultados: La supervivencia al año fue de 90.91% (IC95% 86.40-93.98), a los 3 años 83.64% (IC95% 77.89-88.01) y a los 5 años de 79.18% (IC95% 72.54-84.39). Los principales factores pronósticos fueron el antecedente de ascitis (HR 2.449, IC 1.252 – 4.792), la edad del donante (HR 1.040, IC 1.009 – 1.071) y el receptor (HR 1.037, IC 1.014 – 1.060). Se encontró una mayor supervivencia en los pacientes con cirrosis alcohólica (HR 0.099, IC 0.021 – 0.467). Conclusiones: El estudio mostró una supervivencia mayor a la reportada en estudios realizados en Estados Unidos (67.4-73.0% a los 5 años) y España (73,3% a los 3 años) y similar a la de Chile (80.0% a los 5 años). Cabe resaltar que estos estudios incluyeron series más grandes de pacientes.

Prevalencia de enfermedad de Fabry en pacientes en lista de trasplante y posttrasplante renal en fundación cardioinfantil Bogotá

Introducción: La Enfermedad de Fabry (EF), es una enfermedad multisistémica de almacenamiento lisosomal ligada al cromosoma X que afecta principalmente a hombres, pero también puede causar significativa morbilidad en las mujeres heterocigotas (1–5). La deficiencia de la enzyma α-galactosidaseA (α-Gal A,) provoca acumulación de glicosfingolipidos que afectan diferentes tipos celulares entre ellos el endotelio vascular en vasos de pequeño calibre, células epiteliales y Músculo liso en el sistema cardiovascular (cardiomiocitos), sistema nervioso y células epiteliales tubulares del riñón (6,7). Complicaciones como la falla renal es la causa de muerte más frecuente en la EF (7,8). La incidencia se ha calculado en 1 de cada 117.000 nacidos vivos. (9). Objetivos: Determinar la prevalencia de la Enfermedad de Fabry en pacientes con Insuficiencia renal terminal que se encuentren en lista de trasplante y Post-trasplante Renal en Fundación Cardioinfantil Bogotá. Materiales y Métodos: Se realizó un estudio observacional en donde se evaluó la prevalencia de la EF en todos los sujetos mayores de 18 años que se encuentren en lista de trasplante y post-trasplante renal. Resultados: La prevalencia de Enfermedad de Fabry en 98 pacientes con enfermedad renal crónica fue de 7.1% para la muestra general y 12.9% para la muestra con etiología idiopática Conclusiones: La Enfermedad de Fabry es una importante casusa de Enfermedad Renal Crónica Terminal principalmente en el grupo de etiología idiopática. Palabras Clave: Enfermedad de Fabry (FA)

Autosomal dominant polycystic kidney disease in hemodialysis patients in southern Brazil

Introduction: Autosomal dominant polycystic kidney disease is the most common hereditary renal disease in humans. Objective: To examine the prevalence, clinical and laboratory characteristics of patients with polycystic kidneys and relate disease manifestations by gender. Methods: This was an observational and retrospective study. All the medical records of patients with polycystic kidneys who initiated hemodialysis between 1995 and 2012, in four centers that treat patients of the coverage area of the 15th regional health Paraná (Brazil), were analyzed. Results: The study included 48 patients with polycystic kidneys, the primary cause of stage 5 CKD. Disease prevalence was one in 10,912 people. The average age of dialysis initiation was 50.7 years and the follow-up time on dialysis until transplantation (36.5 months) was lower among men. Hypertension was the most frequent diagnosis in 73% of patients, predominantly in women (51.4%). The liver cyst was the most frequent extrarenal manifestations in men (60.0%). The death occurred in 10.4% of patients using hemodialysis, and 60% of men. The class of antihypertensive drug used was that acts on the renin-angiotensin system with higher frequency of use among women (53.3%). The post-dialysis urea was significantly higher in men. Conclusion: The prevalence of the disease is low among hemodialysis patients in southern Brazil. The differences observed between genders, with the exception of the post-dialysis urea, were not significant. The findings are different from those reported in North America and Europe.

Omega-3 fatty acids, cardiovascular disease and stability of atherosclerotic plaques

Long-chain n-3 polyunsaturated fatty acids are found in oily fish and in fish oils and similar preparations. Substantial evidence from epidemiological and case-control studies indicates that consumption of fish, oily fish and long-chain n-3 fatty acids reduces risk of cardiovascular mortality. Secondary prevention studies using long-chain n-3 fatty acids in patients post-myocardial infarction have shown a reduction in total and cardiovascular mortality with an especially potent effect on sudden death. Long-chain n-3 fatty acids have been shown to beneficially modify a range of cardiovascular risk factors, which may result in primary cardiovascular prevention. However, reduced non-fatal and fatal events and a reduction in sudden death probably involve other mechanisms. Reduced thrombosis following long-chain n-3 fatty acids may play a role. A decrease in arrhythmias is a favoured mechanism of action of long-chain n-3 fatty acids and is supported by cell culture and animal studies. However human trials using implantable cardiac defibrillators have produced inconsistent findings and a recent meta-analysis does not support this mechanism of action. An alternative mechanism of action may be stabilisation of atherosclerotic plaques by long-chain n-3 fatty acids. This is suggested by one published human study which showed that incorporation of long-chain n-3 fatty acids into plaques collected at carotid endarterectomy resulted in fewer macrophages in the plaque and a morphology indicative of increased stability. These findings are supported from observations in an animal model and suggest that the primary effect of long-chain n-3 fatty acids might be on macrophages within the plaque.

Fungicide and cultivar affect post-anthesis patterns of nitrogen uptake, remobilization and utilization efficiency in wheat

Three successive field experiments (2000/01-2002/03) assessed the effect of wheat cultivar (Consort.. Hereward and Shamrock) and fungicide (epoxiconazole and azoxystrobin) applied at and after flag leaf emergence on the nitrogen in the above-ground crop (Total N) and grain (Grain N), net nitrogen remobilization from non-grain tissues (Remobilized N). grain dry matter (Grain Dill), and nitrogen utilization efficiency (NUtE(g) = Grain DM/Total N). Ordinary logistic curves were fitted to the accumulation of Grain N, Grain DM and Remobilized N against thermal time after anthesis and used to simultaneously derive fits for Total N and NUtE(g). When disease was controlled, Consort achieved the greatest Grain DM, Total N, Grain N and NUtEg; in each case due mostly to longer durations, rather than quicker rates, of accumulation. Fungicide application increased final Grain Dill.. Grant N, Total N and Remobilized N, also mostly through effects on duration rather than rate of accumulation. Completely senesced leaf laminas retained less nitrogen when fungicide had been applied compared with leaf laminas previously infected severely with brown rust (Puccinia recondita) and Septoria tritici, or with just S. tritici. Late movement of nitrogen out of fungicide-treated laminas contributed to extended duration of both nitrogen remobilization and grain N filling, and meant that increases in NUtE(g) could occur without simultaneous reductions in grain N concentration.

Use of essential and molecular dynamics to study gamma B-crystallin unfolding after non-enzymic post-translational modifications

Essential and Molecular Dynamics (ED/MD) have been used to model the conformational changes of a protein implicated in a conformational disease-cataract, the largest cause of blindness in the world-after non-enzymic post-translational modification. Cyanate modification did not significantly alter flexibility, while the Schiff's base adduct produced a more flexible N-terminal domain, and intra-secondary structure regions, than either the cyanate adduct or the native structure. Glycation also increased linker flexibility and disrupted the charge network. A number of post-translational adducts showed structural disruption around Cys15 and increased linker flexibility; this may be important in subsequent protein aggregation. Our modelling results are in accord with experimental evidence, and show that ED/MD is a useful tool in modelling conformational changes in proteins implicated in disease processes. (C) 2003 Published by Elsevier Ltd.

Exaggerated postprandial lipaemia and lower post-heparin lipoprotein lipase activity in middle-aged men

An exaggerated postprandial lipaemic response is thought to play a central role in the development of an atherogenic lipoprotein phenotype, a recognized lipid risk factor for coronary heart disease. A small number of limited studies have compared postprandial lipaemia in subjects of varying age, but have not investigated mechanisms underlying age-associated changes in postprandial lipaemia. In order to test the hypothesis that impaired lipaemia in older subjects is associated with loss of insulin sensitivity, the present study compared the postprandial lipaemic and hormone responses for 9 h following a standard mixed meal in normolipidaemic healthy young and middle-aged men. Lipoprotein lipase (LPL) and hepatic lipase (HL) activities were determined in post-heparin plasma 9 h postprandially and on another occasion under fasting conditions. Postprandial plasma glucose (P < 0.02), retinyl ester (indirect marker for chylomicron particles; P < 0.005) and triacylglycerol (TAG)-rich lipoprotein (density < 1.006 g/ml fraction of plasma) TAG (P < 0.05) and retinyl ester (P < 0.005) responses were higher in middle-aged men, whereas plasma insulin responses were lower in this group (P < 0.001). Fasting and 9 h postprandial LPL and HL activities were also significantly lower in the middle-aged men compared with the young men (P < 0.006). In conclusion, the higher incremental postprandial TAG response in middle-aged men than young men was attributed to the accumulation of dietary-derived TAG-rich lipoproteins (density < 1.006 g/ml fraction of plasma) and occurred in the absence of marked differences in fasting TAG levels between the two groups. Fasting and postprandial LPL and HL activities were markedly lower in middle-aged men, but lack of statistical associations between measures of insulin response and post-heparin lipase activities, as well as between insulin and measures of postprandial lipaemia, suggest that this lower activity cannot be attributed to lack of sensitivity of lipases to activation by insulin. Alternatively, post-heparin lipase activities may not be good markers for the insulin-sensitive component of lipase that is activated postprandially.

The use of proteomics to identify novel therapeutic targets for the treatment of disease

The completion of the Human Genome Project has revealed a multitude of potential avenues for the identification of therapeutic targets. Extensive sequence information enables the identification of novel genes but does not facilitate a thorough understanding of how changes in gene expression control the molecular mechanisms underlying the development and regulation of a cell or the progression of disease. Proteomics encompasses the study of proteins expressed by a population of cells, and evaluates changes in protein expression, post-translational modifications, protein interactions, protein structure and splice variants, all of which are imperative for a complete understanding of protein function within the cell. From the outset, proteomics has been used to compare the protein profiles of cells in healthy and diseased states and as such can be used to identify proteins associated with disease development and progression. These candidate proteins might provide novel targets for new therapeutic agents or aid the development of assays for disease biomarkers. This review provides an overview of the current proteomic techniques available and focuses on their application in the search for novel therapeutic targets for the treatment of disease.

For better or worse: the effect of levodopa on speech in Parkinson's disease

While the beneficial effect of levodopa on traditional motor control tasks have been well documented over the decades. its effect on speech motor control has rarely been objectively examined and the existing literature remains inconclusive. This paper aims to examine the effect of levodopa on speech in patients with Parkinson's disease. It was hypothesized that levodopa would improve preparatory motor set related activity and alleviate hypophonia. Patients fasted and abstained from levodopa overnight. Motor examination and speech testing was performed the following day, pre-levodopa during their "off' state, then at hourly intervals post-medication to obtain the best "on" state. All speech stimuli showed a consistent tendency for increased loudness and faster rate during the "on" state, but this was accompanied by a greater extent of intensity decay. Pitch and articulation remained unchanged. Levodopa effectively upscaled the overall gain setting of vocal amplitude and tempo, similar to its well-known effect on limb movement. However, unlike limb movement, this effect on the final acoustic product of speech may or may not be advantageous, depending on the existing speech profile of individual patients. (C) 2007 Movement Disorder Society.

Cognitive follow up of a small cohort of Huntington's disease patients over a 5 year period

A small group of patients with manifest Huntington's disease (HD) were followed longitudinally to assess cognitive decline in relation to time from disease diagnosis. This article looks at performance on a range of computerised and pencil and paper cognitive tasks in patients 5 years post diagnosis, who were assessed annually for a 5 year follow up period. The almost universal cognitive decline reported in other longitudinal studies of HD was not replicated in this study. It was proposed that longitudinal follow up in HD is complicated by the varying degree to which different tasks are able to withstand repeated administration; a finding which would have significant implications on study design in future trials of cognitive enhansing interventions.

Animal disease and the limits of local knowledge: dealing with ticks and tick-borne diseases in South Africa

Some proponents of local knowledge, such as Sillitoe (2010), have expressed second thoughts about its capacity to effect development on the ‘revolutionary’ scale once predicted. Our argument in this article follows a similar route. Recent research into the management of livestock in South Africa makes clear that rural African livestock farmers experience uncertainty in relation to the control of stock diseases. State provision of veterinary services has been significantly reduced over the past decade. Both white and African livestock owners are to a greater extent left to their own devices. In some areas of animal disease management, African livestock owners have recourse to tried-and-tested local remedies, which are largely plant-based. But especially in the critical sphere of tick control, efficacious treatments are less evident, and livestock owners struggle to find adequate solutions to high tickloads. This is particularly important in South Africa in the early twenty-first century because land reform and the freedom to purchase land in the post-apartheid context affords African stockowners opportunities to expand livestock holdings. Our research suggests that the limits of local knowledge in dealing with ticks is one of the central problems faced by African livestock owners. We judge this not only in relation to efficacy but also the perceptions of livestock owners themselves. While confidence and practice varies, and there is increasing resort of chemical acaricides we were struck by the uncertainty of livestock owners over the best strategies.

Orange juice–derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: a randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease

Background: Epidemiological data suggest inverse associations between citrus flavanone intake and cardiovascular disease (CVD) risk. However, insufficient randomized controlled trial (RCT) data limit our understanding of mechanisms by which flavanones and their metabolites potentially reduce cardiovascular (CV) risk factors. Objective: We examined the effects of orange juice or a dose-matched hesperidin supplement on plasma concentrations of established and novel flavanone metabolites and their effects on CV risk biomarkers in men at moderate CVD risk. Methods: In an acute, randomized, placebo-controlled crossover trial, 16 fasted participants (aged 51-69 y) received orange juice or a hesperidin supplement (both providing 320 mg hesperidin) or control (all matched for sugar and vitamin C content). At baseline and 5 h post-intake, endothelial function (primary outcome), further CV risk biomarkers (i.e. blood pressure, arterial stiffness, cardiac autonomic function, platelet activation and NADPH oxidase gene expression) and plasma flavanone metabolites were assessed. Prior to each intervention, a diet low in flavonoids, nitrate/nitrite, alcohol and caffeine was followed and a standardized low-flavonoid evening meal was consumed. Results: Orange juice intake significantly elevated mean (± SEM) plasma concentrations of 8 flavanone (1.75 ± 0.35 µmol/L, P < 0.0001) and 15 phenolic metabolites (13.27 ± 2.22 µmol/L, P < 0.0001) compared with control at 5 h post-consumption. Despite increased plasma flavanone and phenolic metabolite concentrations, CV risk biomarkers were unaltered. Following hesperidin supplement intake, flavanone metabolites were not different to control, suggesting altered absorption/metabolism compared with the orange juice matrix. Conclusions: Following single-dose flavanone intake within orange juice, we detected circulating flavanone and phenolic metabolites collectively reaching a concentration of 15.20 ± 2.15 µmol/L but observed no effect on CV risk biomarkers. Longer-duration RCTs are required to further examine the previous associations between higher flavanone intakes and improved cardiovascular health and to ascertain the relative importance of food matrix and flavanone-derived phenolic metabolites.