Estatinas en enfermedad renal crónica / Statins in chronic kidney disease

La enfermedad renal crónica constituye una patología de prevalencia e impacto creciente en la población mundial por sus múltiples complicaciones, incluyendo un riesgo cardiovascular aumentado, que representa la principal causa de morbimortalidad en pacientes nefrópatas crónicos. Sin embargo, la relevancia de las dislipidemias, especialmente, la hipercolesterolemia LDL, en el deterioro de la función renal y desarrollo de ateroesclerosis en sujetos con daño renal crónico no ha sido claramente establecida. Esta situación ha generado controversia sobre el beneficio real del uso de hipolipemiantes en estos pacientes. En base a la evidencia disponible, incluyendo estudios clínicos recientes, la recomendación más apropiada sugiere que el uso de terapia hipolipemiante basada en estatinas (con o sin ezetimiba) es beneficioso desde un punto de vista cardiovascular en nefrópatas crónicos con insuficiencia renal leve a moderada antes de la diálisis. Por otro lado, no existe evidencia definitiva para apoyar el uso rutinario de este tipo de hipolipemiantes en el manejo del deterioro de la filtración glomerular y/o la proteinuria. Basándose en la evidencia analizada en esta revisión, las futuras guías clínicas para el manejo del daño renal crónico deberán incorporar el uso de estatinas y/o ezetimiba como un elemento más dentro del armamento terapéutico de este tipo de pacientes.(AU)

Chronic kidney disease is a condition of increasing prevalence and impact on the world population by its many complications, including increased cardiovascular risk that represents the leading cause of morbidity and mortality in chronic nephropathy patients. However, the relevance of dyslipidemia, especially high LDL cholesterol, in the impairment of renal function and development of atherosclerosis in subjects with chronic kidney disease has not been clearly established. This situation has generated controversy regarding the real benefit of use of lipid-lowering therapy in these patients. Based on available evidence, including recent clinical studies, the most appropriate recommendation suggests that the use of lipid-lowering therapy based on statins (with or without ezetimibe) is beneficial from a cardiovascular standpoint in chronic nephropathy with mild to moderate renal failure before dialysis. On the other hand, there is no definitive evidence to support the routine use of lipid lowering drugs in the management of impaired glomerular filtration and/or proteinuria. Based on the evidence discussed in this review, future clinical guidelines for management of chronic renal damage should incorporate the use of statins and/or ezetimibe as a key element in the therapeutic armamentarium to be applied in these patients.(AU)

Perfil lipídico en mujeres embarazadas sanas de tres regiones de Chile / Lipid profile in healthy pregnant women in three regions of Chile

Antecedentes: Los lípidos plasmáticos maternos durante el embarazo pueden influir en el crecimiento fetal, particularmente en pacientes con diabetes gestacional; estos lípidos cambian su concentración plasmática materna a lo largo de la gestación. Objetivo: Calcular tablas y curvas de lípidos normales según edad gestacional en una población de embarazadas chilenas. Método: Se midió el colesterol total (CT), colesterol LDL (LDL-C) triglicéridos (TG), Colesterol-HDL (HDL-C), y ácidos grasos no esterificados (NEFA), en 94 embarazadas sanas y jóvenes (<33 años, edad media de 27,6 +/- 6,2 años), con peso pregestacional normal (Índice de Masa Corporal entre 20 y 24,9 Kg/m2 y medio de 23,3 +/- 2,0 Kg/m2). Las pacientes provenían de: Hospital Parroquial de San Bernardo, Santiago (n=55), Hospital de Talca (n=2); Hospital del Profesor, Santiago (n=18); Hospital Regional de Concepción (n=9) y Hospital Clínico de la Pontificia Universidad Católica de Chile (n=10). Resultados: Calculamos, para cada uno de los cuatro lípidos, las curvas de percentil 50, percentil 90 y percentil 10, en mg/dL y mmol/l. Los NEFA solo fueron expresados en mmol/l. Incluimos las funciones matemáticas de las curvas de regresión polinomial de los cuatro lípidos con el fin que sean fácilmente reproducibles en otros tamaños. Conclusiones: Calculamos las tablas y curvas de lípidos maternos normales a lo largo del embarazo, que sean aplicables a la población de embarazadas chilenas.

Background: In normal human pregnancy, maternal lipids can modify the rate of fetal growth, particularly in pregnancies with Gestational Diabetes Mellitus (GDM). These lipids change continuously their serum concentration in the mother along the pregnancy. Aim: To calculate tables and curves of normal serum lipids, according to gestational age, in healthy Chilean pregnant women. Methods: We measured total cholesterol (CT), LDL-cholesterol (LDL-C), triglycerides (TG), HDL-Cholesterol (HDL-C), and Non-Esterified Fatty Acids (NEFA) in 94 young and healthy pregnant women (< 33 years, mean age 27.6 +/- 6.2 years), with normal pregestational Body Mass Index (BMI, 20.0-24.9 Kg/m2 , mean value= 23.3 +/- 2.0 Kg/m2). The women of the study were patients of 5 hospitals: Hospital Parroquial de San Bernardo, Santiago (n=55), Hospital de Talca (n=2); Hospital del Profesor, Santiago (n=18); Hospital Regional de Concepción (n=9) and Hospital Clínico de la Pontificia Universidad Católica de Chile (n=10). Results: For each one of the lipids, we calculated curves of 50th, 90th and 10th percentiles, both in mg/dL and mmol/L (the NEFA were expressed only in mmol/L). The mathematical functions of the curves of polynomial regression of all lipids were included in the manuscript, in order to facilitate their reproduction. Conclusions: We calculated tables and curves of normal maternal serum lipids in relation to gestational, in order to make these available for use in the care of Chilean pregnant women.

[Applying positive psychology to medical education]. / Aplicando psicología positiva en educación médica.

Today we are witnessing an exponential growth in positive psychology (PP), a scientific approach to the most significant purpose of human existence: happiness and meaning of life. As a consequence of PP studies, happiness and wellbeing are now accepted as valid topics of research, despite their subjective and supposedly unscientific essence. Experimental evident indicates that happiness and wellbeing have biological bases and, thus, can be scientifically approached and eventually changed. We believe that we need to learn from this new discipline and apply its discoveries in our profession as medical educators to foster the full development of our students. In this review, we will summarize the major developments and discoveries of PP, and open the debate on the implications of PP offer to medical education.

Aplicando psicología positiva en educación médica / Applying positive psychology to medical education

Today we are witnessing an exponential growth in positive psychology (PP), a scientific approach to the most significant purpose of human existence: happiness and meaning of life. As a consequence of PP studies, happiness and wellbeing are now accepted as valid topics of research, despite their subjective and supposedly unscientific essence. Experimental evident indicates that happiness and wellbeing have biological bases and, thus, can be scientifically approached and eventually changed. We believe that we need to learn from this new discipline and apply its discoveries in our profession as medical educators to foster the full development of our students. In this review, we will summarize the major developments and discoveries of PP, and open the debate on the implications of PP offer to medical education.

[Molecular diagnosis and combined lipid lowering therapy of heterozygous familial hypercholesterolemia. Report of one case]. / Hipercolesterolemia familiar heterocigota: diagnóstico molecular y terapia combinada. Caso clínico.

Heterozygous familial hypercholesterolemia affects one every 400 individuals, is caused by mutations in the LDL receptor gene and is associated with premature coronary artery disease. Nowadays, LDL cholesterol can be efficiently reduced with the new therapies to reduce blood lipids. We report a female patient who consulted in 1975, when she was 46 years old, for severe hypercholesterolemia. In 2003, a sample of leukocyte DNA was obtained and the uncommon 1705+1G>A mutation of the LDL receptor gene was detected. No mutations in the apolipoprotein B gene were found. The patient was treated successfully with simvastatin 80 mg/day and ezetimibe 10 mg/day and LDL cholesterol levels were reduced below 200 mg/dl.

Hipercolesterolemia familiar heterocigota: diagnóstico molecular y terapia combinada. Caso clínico / Molecular diagnosis and combined lipid lowering therapy of heterozygous familial hypercholesterolemia: Report of one case

Heterozygous familial hypercholesterolemia affects one every 400 individuals, is caused by mutations in the LDL receptor gene and is associated with premature coronary artery disease. Nowadays, LDL cholesterol can be efficiently reduced with the new therapies to reduce blood lipids. We report a female patient who consulted in 1975, when she was 46 years old, for severe hypercholesterolemia. In 2003, a sample of leukocyte DNA was obtained and the uncommon 1705 + 1G >A mutation of the LDL receptor gene was detected. No mutations in the apolipoprotein B gene were found. The patient was treated successfully with simvastatin 80 mg/day and ezetimibe 10 mg/day and LDL cholesterol levels were reduced below 200 mg/dl.

[Intensive cholesterol lowering therapy to reduce cardiovascular risk]. / Terapia hipolepemiante intensiva en el manejo del riesgo cardiovascular ateroesclerótico.

Primary and secondary prevention trials have clearly demonstrated that lowering serum cholesterol levels with statins reduces the incidence of cardiovascular events. Recent studies plus post hoc analysis of previous clinical trials show that risk reduction is proportional to the magnitude of LDL cholesterol lowering. Therefore, new recommendations of the National Cholesterol Education Program (USA) have defined a category of patients with very high cardiovascular risk, who should achieve serum LDL cholesterol levels below 70 mg/dl. This proposal will require new and more efficient pharmacologic strategies to attain the increasingly strict therapeutic goals for LDL cholesterol. This article reviews the clinical studies that support the use of intensive lipid lowering therapy to reduce cardiovascular risk. An effective reduction of serum cholesterol can be obtained using statins in high doses or a combination of hypolipidemic drugs with different mechanisms of action.

Terapia hipolepemiante intensiva en el manejo del riesgo cardiovascular ateroesclerótico / Intensive cholesterol lowering therapy to reduce cardiovascular risk

Primary and secondary prevention trials have clearly demonstrated that lowering serum cholesterol levels with statins reduces the incidence of cardiovascular events. Recent studies plus post hoc analysis of previous clinical trials show that risk reduction is proportional to the magnitude of LDL cholesterol lowering. Therefore, new recommendations of the National Cholesterol Education Program (USA) have defined a category of patients with very high cardiovascular risk, who should achieve serum LDL cholesterol levels below 70 mg/dl. This proposal will require new and more efficient pharmacologic strategies to attain the increasingly strict therapeutic goals for LDL cholesterol. This article reviews the clinical studies that support the use of intensive lipid lowering therapy to reduce cardiovascular risk. An effective reduction of serum cholesterol can be obtained using statins in high doses or a combination of hypolipidemic drugs with different mechanisms of action.

El colesterol HDL: ¿un nuevo objetivo terapéutico en el manejo de las dislipidemias y la ateroesclerosis? / HDL cholesterol: A new target in the treatment of lipid disorders and atherosclerosis?

Low plasma HDL cholesterol levels are an independent risk factor for atherosclerotic cardiovascular disease. During the past years, the study of HDL has been stimulated by the discovery of novel genes and proteins, which have provided new insights into the molecular and cellular mechanisms involved in HDL metabolism. In addition, recent clinical studies focused on treating low HDL as primary objective in high cardiovascular risk patients have been very encouraging. Furthermore, new drugs for raising HDL cholesterol are under development. This article reviews the recent progress in the HDL field and its important implications for the pathophysiology and treatment of atherosclerosis. In the near future, we expect that new drugs with specific and beneficial effects on HDL metabolism and the associated cardiovascular risk should improve the current approach to this disease with high burden on health systems and society.

[Physicians in biomedical research in Chile: a species under risk of extinction]. / Médicos-centíficos en Chile: una especie en extinción?

Several studies have reported a progressive reduction in the number of grant applications and research projects approved by medical doctors (MD) in the United States. The overall trend and current situation of MDs actively involved in biomedical research in Chile has not been defined. Thus, we analyzed the professional profile of the principal investigators (PI) that have led research grants approved by the Technology and Medical Sciences study groups of the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT), during the last 20 years. The results show that the projects led by MDs corresponded to 80% in 1984, decreasing to 50% in 2003, with further reduction projected for the next years. We think that the physician doing biomedical research represents a human resource indispensable to preserve a genuine academic environment within medical schools; thus, it is necessary to design and apply strategies to reverse this worrying trend of less MDs actively involved in research in Chile. Among these, we consider important to stimulate research activities at both the undergraduate and postgraduate levels of MD training particularly increasing the flexibility of the postgraduate fellowship programs. In addition, it is necessary to support both in terms of money and spare time those physicians who are beginning an academic career involved in biomedical research. Finally, we consider important that non-academic institutions (e.g., pharmaceutical companies, health medical organizations, and philanthropic foundations) should also support academic development and biomedical research in our medical schools.

Médicos -Centíficos en Chile: ¿Una especie en extinción? / Physicians in biomedical research in Chile: A species under risk of extinction?

Several studies have reported a progressive reduction in the number of grant applications and research projects approved by medical doctors (MD) in the United States. The overall trend and current situation of MDs actively involved in biomedical research in Chile has not been defined. Thus, we analyzed the professional profile of the principal investigators (PI) that have led research grants approved by the Technology and Medical Sciences study groups of the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT), during the last 20 years. The results show that the projects led by MDs corresponded to 80percent in 1984, decreasing to 50percent in 2003, with further reduction projected for the next years. We think that the physician doing biomedical research represents a human resource indispensable to preserve a genuine academic environment within medical schools; thus, it is necessary to design and apply strategies to reverse this worrying trend of less MDs actively involved in research in Chile. Among these, we consider important to stimulate research activities at both the undergraduate and postgraduate levels of MD training particularly increasing the flexibility of the postgraduate fellowship programs. In addition, it is necessary to support both in terms of money and spare time those physicians who are beginning an academic career involved in biomedical research. Finally, we consider important that non-academic institutions (e.g., pharmaceutical companies, health medical organizations, and philanthropic foundations) should also support academic development and biomedical research in our medical schools.

Mecanismos de hipo e hiper alfalipoproteinemia en individuos adultos chilenos / Mechanisms of hypo and hyper alphalipoproteinemia in Chilean adults

Background: High density lipoprotein (HDL) cholesterol is inversely associated to atherosclerotic cardiovascular risk. Disturbances in HDL cholesterol plasma leves are frecuent in the Chilean population, however the pathophysiological mechanisms are unknown. Aim: To evaluate the mechanisms involved in the hypo and hyper alfalipoproteinemias in Chilean subjects. Materials and Methods: Twenty three subjects with hyperalphalipoproteinemia and 12 with hypoalphalipoproteinemia, paired with control subjects (col-HDL between 35 and 55 mg/dl) were studied. We measured plasma lipids, subfractions and sizing of HDL particles and enzymatic activity of cholesteryl ester transfer protein (CETP), lecithin: cholesterol acyltransferase (LCAT), lipoprotein lipase (LPL) and hepatic lipase (LH). Results: Subjects with hyperalphalipoproteinemia showed significantly higher levels of total HDL-cholesterol (70±2 vs 44±1 mg/dl), HDL 2 (30±3 vs 5±1 mg/dl), Apo A I (175±3 vs 146±4 mg/dl), lower HL activity (23,7±0,8 vs 32,4±1,8 mmol/h/l) and HDL particles of greater size, compared to their controls. Subjects with hypoalphalipoproteinemia, showed significantly lower levels of total HDL-cholesterol (26±1 vs 48±2 mg/dl), HDL 3 (21±1 vs 40±2 mg/dl), Apo A I (107±5 vs 145±7 mg/dl), lower LCAT activity (18,6±1,9 vs 26,2±1,6 nmol/h/ml) and smaller HDL particles, compared to their controls. Conclusion: Changes in hepatic lipase and lecithin cholesterol acyltransferase activities may explain the hyper and hypo alphalipoproteinemia respectively, in Chilean subjects.

Medicina molecular: presente y futuro / Molecular medicine: present and future

The genetic background of individuals is recognized as an important clue in the analysis of classical hereditary and multifactorial acquired diseases. This new concept derives from the development and increasing use of molecular genetics in clinical medicine. The application of molecular biology techniques in biomedical investigation has encompassed the identification of the pathogenesis and etiology of diseases, prenatal diagnosis the production of new therapeutic agents, gene therapy and the development of pharmacogenetics. The impact on the fundamentals and practice of clinical medicine that will have the use of molecular biology is analyzed in this review

Biología molecular y medicina: conceptos básicos / Molecular biology and medicine: basic concepts

Through the advancements of molecular genetics, physicians and researchers are in an extraordinary period of study concerning the molecular basis of medicine. Molecular biology is making a tremendous impact on both diagnosis and treatment of diseases through the clinical introduction of molecular methods. These techniques, restricted for many years to basic biological research, include the polymerase chain reaction, DNA and protein electrophoresis, cloning of genes into viral or bacterial vectors and methods to rapidly sequence DNA and identify mutations. In this article the authors attempt to provide basic concepts on these themes for the non-trained physicians in order to help them to understand recent developments and foresee their future implications