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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 years period during which any adverse event is assumed to have been caused by the medication or device 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 device 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, or 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.

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.

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 is provided by the two main advocates of these ideas: Gandhi and Darwin. The cognate factors that determine immunological tolerance (IT), systemic (SA) and local adaptation (LA) are multiple; 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 expansion, 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 invasion and uterine artery transformation is supported. The relevance of an adequate adaptation to pregnancy is highlighted not only by the intragestational complications derived from a defective process, such as intrauterine growth restriction, preterm birth, and preeclampsia -its foremost expression- but also by the long term cardiovascular complications of the mother and her offspring.

Background: During the years 2008 and 2009, 1191 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 Medica de Chile and Revista Chilena de Infectologia 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 focused in reaching local readers. The evaluation of research productivity should combine several scientometric indexes, selected according to the field of research, the institutional and investigators’ interests, with a qualitative and multifactorial appreciation.

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).

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

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 Med Chile 2003; 131: 1429-33)

Based on two patients, we discuss the difficulties in diagnosing and managing primary aldosteronism in pregnancy, which derive from changes of the renin-angiotensin-aldosterone axis, from the uncertainty regarding blood pressure control along gestation and postpartum, and from the contraindication to the use of spironolactone. The first case is a 27 years old woman with a long standing refractory hypertension, a hemorrhagic stroke with left brachial hemiplegia and crural hemiparesia, two miscarriages, one stillbirth and one offspring with intrauterine growth retardation. Due to hypokalemia, a plasma aldosterone/renin activity ratio of 91, and a negative genetic screening for glucocorticoid remediable aldosteronism (GRA), a primary hyperaldosteronism with normal adrenals in CT scan was diagnosed, and good blood pressure control was attained with spironolactone. After two and a half years of normotension, a fifth pregnancy, managed with methyldopa evolved with satisfactory blood pressures, plasma potassium, fetal growth, uterine and umbilical arterial resistance indexes, and maternal endothelial function. At 37 1/2 weeks of pregnancy the patient delivered a healthy newborn weighing 2,960 g. Blood pressure rose during the 48 hours of postpartum in the absence of proteinuria and required iv hydralazine. The second patient is a 37 years old woman, with known refractory hypertension for 7 years, hypokalemia, plasma aldosterone/renin activity ratio greater than 40, normal adrenals in the CAT scan, and a negative genetic screening for GRA. She had normotensive pregnancies 5 and 3 years prior to the detection of hypertension, with hypertensive crisis in both postpartum periods, retrospectively considered as expressions of primary hyperaldosteronism (Rev Med Chile 2002; 130: 1399-1405)

The management of severe hypertension in the emergency setting demands a careful evaluation of the different underlying clinical situations, and of the impending risk for the life of the patient or of acute organ damage. Hypertensive emergencies and urgencies have to be identified, and distinguished from chronic severe hypertension, a frequent presentation to the emergency services. A thorough clinical evaluation, and not the magnitude of the blood pressure elevation, should be the basis of the differential diagnosis; this will guide the setting required for treatment (intensive care unit, ward or ambulatory), the drugs of choice, as well as the velocity of blood pressure reduction. Special emphasis has to be given to the management of cerebrovascular accidents and severe preeclampsia, as the reduction of blood pressure entails a risk of hypoperfusion of critical territories as the brain and fetus respectively. A wide range of drugs permits a tailored treatment of a variety of clinical situations. Efforts have to be made to detect and manage chronic hypertensive patients in order to reduce the consultation load represented by severe hypertensives in emergency services, by preventing hypertensive crisis, in order to focalize on real situations of risk (Rev Méd Chile 2002; 130: 322-31)

A 36 year old woman, with an 18 year history of syncope, became pregnant shortly after a cardiac catheterization demonstrated a high pulmonary arterial pressure and resistance and a low cardiac output. During pregnancy she remained stable at NYHA FC III, on nifedipine, apresoline, isosorbide, aspirin and bed rest. At 28 weeks, catheterization showed a decreased pulmonary pressure and an increased cardiac output. At 38 weeks, she was submitted to an elective caesarean section, and delivered a healthy newborn of 2820 g. After 5 months, her catheterization showed a pulmonary artery pressure similar to the pre-pregnancy study. Her condition deteriorated, leading to death 10 months later. Urinary 6-keto-PGF1∂, nitrates/nitrites, kallikrein and angiotensin-(1-7) were increased from 13 to 33 weeks, to drop in week 35 of pregnancy. The safe maternal and fetal outcome, and the intragestational hemodynamic improvement are attributed to a close multidisciplinary surveillance, and to the effects of the endogenous vasodilators of pregnancy on the reversible component of the pulmonary hypertension. Reports in the literature show a decrease in maternal mortality rate, from 56% for the period previous to 1963, to 34 and 30% for those spanning between 1978-1996 y 1997-2001 respectively (Rev Méd Chile 2002; 130: 201-8)

Resistant arterial hypertension is uncommon when there is good compliance to antihypertensive therapy and secondary causes have been ruled out. We report a 41 years old male that suffered hypertensive encephalopathy and received prophylactic anticonvulsant therapy showing progressive raise of arterial pressure levels. Renovascular hypertension, aldosteronism and pheochromocytoma were discarded and, in spite of combined use of antihypertensive drugs, he did not achieve normal blood pressure. When phenytoin was discontinued, blood pressure temporarily normalized. Carbamazepine was started and blood pressure raised again. lt fell when this medication was discontinued. Antiepileptic agents could induce drug metabolizing system and thus reduce the effects of antihypertensive medications. (Rev Méd Chile 2001; 129: 1325-7)

Continuous ambulatory blood pressure monitoring is a diagnostic technique devised as a consequence of the great variations in blood pressure measurements. It allows multiple daily measurements, nocturnal monitoring, avoids the stress of blood pressure measurements, gives a picture of pressure behavior during 24 hours and reduces observer related errors. The equipment used must be accurate and validated using international protocols. Accepted indications for continuous ambulatory blood pressure monitoring are white coat hypertension, episodic hypertension, resistance to medications and assessment of symptoms or autonomic dysfunction. Other indications with less clear cut usefulness, are high risk cardiac, renal or pregnant patients and an accurate blood pressure control. We describe equipment calibration, elements that must be considered in the reports, result interpretation and conclusions. Normal blood pressure ranges for children and pregnant women are also reported.