Preeclampsia y enfermedad cardiovascular: un enfoque integral para detectar las fases subclínicas de complicaciones obstétricas y cardiovasculares / Preeclampsia and cardiovascular disease: an integrated approach to detect the subclinical stages of obstetrical and cardiovascular complications

Desde 1995 hasta la fecha la asociación entre patologías derivadas los embarazos hipertensivos y las enfermedades cardiovasculares ha generado un gran volumen de potentes evidencias epidemiológicas y clínicas. Los propósitos de esta revisión son varios. Mostrar la consistencia y magnitud de la evidencia científica. Integrar los riesgos/enfermedades cardiovasculares y los problemas obstétricos a través de la disfunción endotelial. Preconizar el seguimiento postparto de la hipertensa embarazada, como una ventana de oportunidad para beneficiar la salud de las mujeres y sus hijos. Incluir la historia obstétrica como factor de riesgo de enfermedad coronaria. Proponer cuestionarios adaptables a las prácticas locales para facilitar la pronta incorporación de los índices de riesgo obstétrico y cardiovascular en dos etapas de la vida de una mujer. Ha llegado el momento para que los equipos obstétricos, cardiológicos y las pacientes jueguen un rol en la prevención de los riesgos y enfermedades cardiovasculares.

From 1995 onwards the association between hypertensive pregnancies and cardiovascular disease has generated a great volume of epidemiologic and clinical evidence. The purposes of this review are several. To demonstrate the consistence and weight of the scientific evidence. To integrate cardiovascular risks/diseases and obstetric complications through the link of endothelial dysfunction. To advocate postpartum follow-up after a hypertensive pregnancy as a window of opportunity to benefit the health of mothers and offsprings. To include the obstetrical history as a risk factor for coronary disease. To propose questionnaires adaptable to local practices to incorporate cardiovascular and obstetrical indexes in two stages of a woman's lifetime. The time has come for obstetrical teams, cardiologists and patients to play a preventive role regarding cardiovascular risks and diseases.

Declaración de la Academia Chilena de Medicina sobre el Título V de la Ley 20. 850 (Ley Ricarte Soto) y su proyecto de reglamento “De los ensayos clínicos de productos farmacéuticos y elementos de uso médico” / Declaration of the Chilean Academy of Medicine of Law 20. 850 On clinical trials of pharmaceutical products and medical devices” and of the bylaw that will regulate its application

In Chile, high cost treatments required by selected medical conditions are financed by the State, according to Law 20.850. A bylaw under discussion by the Senate regulates clinical trials, posing complex issues that will endanger local interest in front-line research: 1. The exclusive and mandatory control bestowed to the Institute of Public Health during all stages of the trials and also the surveillance of institutions performing clinical trials, overriding their Clinical Research Review Boards; 2.The 10 year period during which any adverse event is assumed to have been caused by the medication or devise evaluated by the trial, unless the contrary is proven in a judicial process; 3. Individuals submitted to the trials are entitled to free post trial access to the treatment received during the study, financed by the trial supporting entities and as long as the drug or devise is considered to be useful. While agreeing with the need to have a National Registry of Clinical Trials, we predict that the mentioned critical issues in the bylaw will lead to difficulties and unnecessary judicial processes, thus limiting clinicians’ interest in performing research. We propose to modify the bylaw, excluding responsibilities on events associated with the natural evolution of the medical condition, with patients’ ageing or with comorbidities and clinical events considered unpredictable when the protocol was accepted. We recommend that the free post trial access should be a joint decision involving the patient and the attending physician, taking in consideration that the volunteer has been exposed to risks and burdens, or when discontinuation of treatment entails a vital risk until the treatment under study has been approved and becomes available in the national market.

Análisis de las publicaciones biomédicas chilenas indizadas en PubMed, en los años 2008 y 2009 / An analysis of Chilean biomedical publications in PubMed in the years 2008-2009

Background: During the years 2008 and 2009, 1,191 biomedical articles authored by Chilean investigators working in Chile were indexed in PubMed. Aims: To evaluate the potential visibility of those articles, according to scientometric indexes of the journals where they were published. Methods: Those journals where the articles had been published were identified and each journal’s Impact Factor (JIF), 5-year JIF, SCImago Journal Rank (SJR), SCImago Quartiles (Q) for 2010 and the Source Normalized Impact per Paper (SNIP) for 2008-2009 were identified. Results: Three hundred and twelve articles (26,2%) were dedicated to experimental studies in animals, tissues or cells and they were classified as “Biomedicine”, while 879 (73,8%) were classified as “Clinical Medicine”; in both areas the main type of articles were original reports (90% and 73.6%, respectively). Revista Médica de Chile and Revista Chilena de Infectología concentrated the greater number of publications. Articles classified in Biomedicine were published more frequently in English and in journals with higher scientometric indexes than those classified in Clinical Medicine. Conclusions: Biomedical articles dealing with clinical topics, particularly case reports, were published mostly in national journals or in foreign journals with low scientometric indexes. It can be partly attributable to the authors’ interest in reaching local readers. The evaluation of research productivity should combine several scientometric indexes, selected according to the field of research, the institution's and investigators’ interests, with a qualitative and multifactorial assessment.

Principales características de la investigación biomédica actual, en Chile / Main characteristics of current biomedical research, in Chile

Background: Biomedical research is a fundamental tool for the development of a country, requiring human and financial resources. Aim: To define some current characteristics of biomedical research, in Chile. Methods: Data on entities funding bio-medical research, participant institutions, and the number of active investigators for the period 2007-2009 were obtained from institutional sources; publications indexed in PubMedfor2008-2009 were analysed. Results: Mostfinancial resources invested in biomedical research projects (approximately US$ 19 million per year) came from the "Comisión Nacional de Investigación Científica y Tecnológica" (CONICYT), a state institution with 3 independent Funds administering competitive grant applications open annually to institutional or independent investigators in Chile. Other sources and universities raised the total amount to US$ 26 million. Since 2007 to 2009, 408 investigators participated in projects funded by CONICYT. The main participant institutions were Universidad de Chile and Pontificia Universidad Católica de Chile, both adding up to 84% of all funded projects. Independently, in 2009,160 research projects -mainly multi centric clinical trials- received approximately US$ 24 million from foreign pharmaceutical companies. Publications listed in PubMed were classified as "clinical research" (n = 879, including public health) or "basic biomedical research" (n = 312). Conclusions: Biomedical research in Chile is mainly supported by state funds and university resources, but clinical trials also obtained an almost equivalent amount from foreign resources. Investigators are predominantly located in two universities. A small number of MD-PhD programs are aimed to train and incorporate new scientists. Only a few new Medical Schools participate in biomedical research. A National Registry of biomedical research projects, including the clinical trials, is required among other initiatives to stimulate research in biomedical sciences in Chile.

El embarazo humano: paradigma biológico de tolerancia y adaptación / Human pregnancy, a biological paradigm of tolerance and adaptation

This review analyses the changes in immunological tolerance, and the systemic and local hemodynamic changes observed along human pregnancy. To underscore the conceptual importance of tolerance and adaptation the background isprovided by the two main advocates ofthese ideas: Gandhi and Darwin. The cognate factors that determine immunological tolerance (IT), systemic (SA) and local adaptation (LA) are múltiple; IT = desensitisation to paternal antigens, absence of HLA-A, roles of HLA-G, natural killer cells and their receptors; SA = decreased vascular resistance, plasma volume expansión, increased cardiac output and plasma renin activity; LA = prostacyclin, nitric oxide, kallikrein-kinin system, vasodilator arm of the renin angiotensin system, vascular endothelial growth factor (VEGF). A possible role of vasodilators in the crucial process of trophoblast invasión and uterine artery transformation is supported. The relevance ofan adequate adaptation to pregnancy is highlighted not only by the intragestational complications derivedfrom a defective process, such as intrauterine growth restriction, preterm birth, and preeclampsia -its foremost expression- but also by the long term cardiovascular complications ofthe mother and her offspring.

Actualización de las recomendaciones sobre el uso de la monitorización ambulatoria de presión arterial. Documento de consenso de la Sociedad Chilena de Hipertensión / Update of consensus reccomendations of the Chilean Hypertension Society about ambulatory blood pressure monitoring

Ambulatory blood pressure monitoring (ABPM) is a valuable tool to evaluate the blood pressure pattern, to identify hypertensive patients, to diagnose white coat and masked hypertension and in situations in which a tight control of hypertension is crucial. This is an update of 1999 consensus recommendations about the use to ABPM, considering that there is new evidence concerning its benefits, and the clinical experience with its application has increased. Equipment programming, its installation, the interpretation and analysis of the data are described, and a report sheet for patients is included. New recommendations have been added to the accepted indications. Normal blood pressure ranges for children and pregnant women have been replaced by new data (Rev Méd Chile 2009; 137:1235-47).

Evaluación ultrasonográfica de la función endotelial en niños y adultos chilenos / Ultrasound assessment of endothelial function in Chilean children and adults

Background: Endothelial dysfunction is an important pathogenetic mechanism in the development of atherosclerosis. Aim: To evaluate endothelial function in Chilean children and adult subjects and to provide normal values of flow mediated dilatation (FMD) in the Chilean population. Subjects and Methods: Flow mediated dilation of the brachial artery was measured by high resolution ultrasonography in healthy children (n=32) and adults (n=69) of both gender, in a group of 8 healthy women during 4 periods of pregnancy and late postpartum, and in 22 men and women with a history of stroke or coronary heart disease. Results: FMD in boys and girls was 9.9±3.6 and 10.0±4.2% respectively (NS). The figures for young women and young men were 11.3±3.8 and 8.6±3.9, respectively (p=0.02); for postmenopausal women and older men, 5.5±6.6 and 7.6±6.7 respectively (NS). During normal pregnancy and postpartum there were no significant changes in FMD. Patients with cardiovascular disease had a FMD of 0.3±5.2%, (p <0.001, with other groups). Conclusions: The present study provides values of FMD in healthy Chilean subjects of different ages, and in patients with coronary heart disease.

Hipotensión ortostática: una manifestación sugerente de feocromocitoma / Orthostatic hypotension: as an unusual manifestation of pheochromocytoma

Pheochromocytoma, though an uncommon cause of hipertension, can be a lethal condition. Because of this it is mandatory to diagnose it or rule it out in presence of suggestive symptoms. Typical symptoms are palpitations, sweating, severe headaches and hypertension. However, there are other suggestive symptoms of this dangerous endocrine entity, one of which is the orthostatic hypotension. We report the case of a 65 years old female patient with long standing hypertension in whom the pheochromocytoma was suspected after episodes of orthostatic hypotension. Although this manifestation was described almost fifty years ago, its frequency and pathophysiology has not yet been well established and fully elucidated. Moreover, it has meaningful implications in relation to preoperatory management and the timing of surgery (Rev Méd Chile 2003; 131: 1429-33).

Efectos nocivos del uso de enalapril sobre la gestación experimental y sus implicancias sobre el uso clínico / Noxious effect of enalapril in experimental pregnancy and clinical implications

Se investigó el efecto del enalapril en la gestación en ratas. A un grupo de 11 ratas se les administró 15 mg/kg/día desde el día primeroal noveno de gestación (E10-20); 12 ratas sirvieron de control (C); 15 animales fueron sacrificados al día 20 y 19 continuaron hasta el parto. Las placentas fueron 15% menores en el grupo E10-20 (p<0.05) y tenían una estructura cordonal hipocelular simple. En el grupo E1-9 el tipo estructural predominante fue una combinación de estructuras simple y compleja. En el día 20 de gestación los fetos de los grupos tratados eran de menor tamaño que los controles (-5% en E1-9 y -16% en E10-20, p<0.05). Las diferencias desaparecieron a los 13 días postparto. En dos fetos tratados se observó calcificación incompleta del cráneo. Estimamos que estos resultados, analizados en el contexto de los daños observados en el embarazo humano, agregan información que fundamenta la abstención del uso de inhibidores de enzima convertidora en el embarazo

Efectos de diltiazem sobre la respuesta adrenérgica y presora en hipertensos, durante el esfuerzo / Diltiazem effects in adrenergic answer of hipertensive patients during effort

El aumento de la actividad adrenérgica contribuye al desarrollo de la Hipertensión Arterial esencial (HTA). La modulación de los niveles plasmáticos de noradrenalina (NAD) durante el esfuerzo submáximo podría ser beneficiosa en la HTA. Hemos evaluado la respuesta presora y adrenérgica de 18 pacientes con HTA leve tratados con Diltiazem o Placebo por un período de 12 semanas, con un protocolo randomizado, cruzado y doble ciego. Se monitorizó la presión arterial (PA) y los niveles plasmáticos de NAD en reposo y durante un esfuerzo submáximo. No se observó diferencia significativa en la frecuencia cardíaca durante los períodos analizados (basal, placebo, diltiazem). Durante la terapia con diltiazem los pacientes normalizaron su presión arterial de reposo, también se observó una disminución de la presión sistólica y diastólica durante el esfuerzo submáximo. La terapia con diltiazem no impidió un incremento significativo de los niveles de NAD durante el esfuerzo leve. Esta respuesta adrenérgica exagerada podría ser deletérea a largo plazo para el sistema cardiovascular de sujetos con HTA

Factores de riesgo de hipertensión arterial en nativos de Isla de Pascua / Risk factors for hypertension in natives from Easter Island

Blood pressure, weight and cardiovascular risk factors were evaluated in 73 adults of Easter island (mean age 49 ñ 12.9 (SD) years) in January 1989 and 1990. Their mean blood pressure (BP) was 129 ñ 24/81 ñ 14, significantly higher by 7/5 mmHg than in 1979 (p < 0.05). Of the population studied 30% of subjects were hypertensives. Both systolic 9S) and diastolic blood pressure (DBP) correlated with age (r=0.40, p < 0.005 and r = 24,p < 0.05 respectively). In males body mass index correlated strongly with SBP and DBP (r = 0.55, p < 0.005 and r = 0.52,p < 0.01). Forty eight % of subjects were obese, 60% smoked (14 cigarettes/day), 38% drank alcohol and 70% lead sedentary lifes; their level of stress was considered average. In 23 normotensives or undiagnosed hypertensives 24 hour urine was collected for sodium, potassium, creatinine and kallikrein; mean urinary sodium exretion was 121 ñ 30 mmol/day; potassium excretion 59 ñ 29 mmol/day, creatinine excretion 1383 mg/day and kallikrein excretion 682 ñ 355 m/day; of these, only urinary sodium was significantly lower than values determined in a group of 29 continental volunteers. Eleven natives that had never left the island had similatr BP and risk factors than a sex and age paired sample, who has spent 10.9 ñ 7.8 years in the continent. The present study demostrates that Easter Island natives have increased their mean BP in 10 years, elevated their BP with age and have lost the protection previously associated to staying in the island. In this sample the prevalence of hypertension (30%) was high. We postulate that the 2 main factors determining the BP elevation are a sodiumintake greater than 100 mmol/day and a high prevalence of obesity, which plays a stronger hypertensogenic role in males. It is highly probable that the contamination is due to returning migrants and to the massive entry of tourists

Criterio alternativo para evaluar la presión arterial en pediatría / Alternative criteria for blood pressure evaluation in children

En pediatría se utiliza el percentil 95 (p95) como método para determinar el límite de presión normal. Con este procedimiento se consideran normales presiones que serían estimadas elevadas en adultos. Buscando una alternativa que no subestime el número de hipertensos se midió la presión arterial a 811 niños sanos del área suroriente de santiago y se estableció como límite normal de presión, los valores que de la media se desviaban 2 veces la desviación estándar (M + 2 DE). Se calculó, por edad y sexo, la mediana, la media, el p 95 y la DE corregidas para muestras pequeñas. Se encontraron diferencias significativas en el número de hipertensos, particularmente, en las edades extremas, empleando ambos métodos: empleando la M + 2 DE se diagnosticaron 78 hipertensos, 9,6% de la población, vs 27 (3,3%) al aplicar el p 95. A los 3,4 y 5 años la aplicación del criterio de M + 2 DE permitió detectar 13,5; 18,0 y 12,1% de casos sospechosos en contraste con sólo 3,4; 4,0 y 15,7% mediante el p 95. A los 16 años el p 95 detectó 2,2% de sujetos con cifras tensionales elevadas contra 13,3 de la M + 2 DE. Esta última cifra es cercana al porcentaje de adultos hipertensos detectados en la población adulta urbana chilena