Mejoría del control de la hipertensión en la consulta con el uso de un dispositivo oscilométrico automático de lectura diferida / Improved office blood pressure control by automatic delayed-reading oscillometric device

Introducción: La medición de la presión arterial (PA) en la consulta es un procedimiento recomendado, aunque, actualmente, se está generalizando el uso de las medidas ambulatorias. Objetivo: Conocer el grado de control de la hipertensión arterial (HTA), usando la medición en la clínica. Material y métodos: Durante noviembre del 2019, se recogieron datos demográficos, clínicos, la PA sistólica (PAS) y diastólica (PAD) en consulta con observador, usando un aparato automático con lectura diferida y datos de monitorización ambulatoria de la PA (MAPA) en caso de haberse realizado. Resultados: Se incluyeron 102 pacientes (67 varones), con edad media de 64,9 años, 30% diabéticos y 34% con complicaciones cardiovasculares. Un 70% tenían una PA clínica controlada (< 140/90 mmHg), la PAS media fue de 131 ± 16,5 mmHg y la PAD de 73 ± 9,5 mmHg. Los pacientes ancianos y diabéticos presentaban un peor control. Treinta y tres sujetos disponían de MAPA, lo que permitió clasificarlos según la PA de 24 horas en: normotensión verdadera 30%, HTA aislada en consulta 9%, HTA sostenida 15% y HTA enmascarada 45%. Conclusión: El uso de aparatos automáticos disminuye el fenómeno de bata blanca mejorando el porcentaje de pacientes con HTA controlada en la consulta. Sin embargo, este control no se confirma fuera de ella, lo que evidencia la importancia de la MAPA en la evaluación global de la HTA. La toma de la PA en la consulta es útil en la valoración inicial del paciente y aporta aspectos educativos, aunque hay que optimizar la metodología para definir su papel en la clínica. (AU)

Introduction: Office blood pressure (BP) measurement is a recommended procedure, although the out-of-office BP measurements are increasingly used. Objective: To know the degree of BP control by clinical measurement. Material and methods: During November 2019 demographic and clinical data, office attended systolic BP (SBP) and diastolic BP (DBP) measured with an automatic device with delayed reading and, if performed, data from ambulatory BP monitoring (ABPM) were collected. Results: 102 patients (67 men) were included, with a mean age of 64.9 years, 30% diabetic and 34% with cardiovascular complications. 70% had a controlled hypertesion (<140/90 mmHg) by office BP, the mean SBP was 131 ± 16.5 mmHg and the DBP was 73 ± 9.5 mmHg. Old age and diabetes were associated with uncontrolled hypertension. Thirty three patients had ABPM data, which allowed them to be classified according to the 24-hour BP into: 30% true normotension, 9% white-coat hypertension, 15% sustained hypertension, and 45% masked hypertension. Conclusion: The use of automatic devices reduces the white-coat phenomenon, improving the % of patients with office BP controlled. However, this is not confirmed outside the clinic, showing the importance of ABPM in the evaluation of hypertension control. Office BP measurement is useful in patients initial assessment and also provides educational aspects, although the methodology must be optimized to define its clinical role. (AU)

Hipertensión del anciano: qué debemos conocer / Hypertension in the elderly: What we need to know

Más de dos terceras partes de los mayores de 65 años son hipertensos. Junto a la elevada prevalencia, la hipertensión se acompaña de comorbilidad que condiciona una población heterogénea en relación con la autonomía y capacidad funcional. En esta edad, la hipertensión tiene unas características que hacen difícil su manejo, destacando la elevada prevalencia de la hipertensión sistólica aislada por la rigidez vascular típica del envejecimiento. Aunque la toma de decisiones se basa en la medida clínica de la presión, se sabe que en los ancianos la presión está sujeta a numerosas influencias tanto temporales (ausencia de descenso nocturno), como del entorno (exacerbación del fenómeno de bata blanca) y de la posición (hipotensión ortostática). Estas circunstancias hay que tenerlas en cuenta a la hora del manejo. En esta edad, hay suficiente evidencia de que el tratamiento reduce tanto la morbimortalidad cardiovascular como la mortalidad por todas las causas. (AU)

More than two thirds of people over 65 are hypertensive. Along with the high prevalence, hypertension is associated by comorbidities that originates a heterogeneous elderly population in relation to their autonomy and functional capacity. At this age, hypertension has special characteristics that make its management difficult, highlighting by isolated systolic hypertension due to the vascular stiffness typical of aging. Although decision-making is based on the clinical measurement of blood pressure, it is known that in the elderly pressure is subject to numerous influences: temporal (absence of night dipping), of the environment (exacerbation of the white coat phenomenon) and of the position (orthostatic hypotension). These circumstances must be taken into account when evaluating and deciding on therapy. At this age, there is sufficient evidence that treatment reduces both cardiovascular morbimortality and all-cause mortality. (AU)

[Improved office blood pressure control by automatic delayed-reading oscillometric device]. / Mejoría del control de la hipertensión en la consulta con el uso de un dispositivo oscilométrico automático de lectura diferida.

INTRODUCTION: Office blood pressure (BP) measurement is a recommended procedure, although the out-of-office BP measurements are increasingly used. OBJECTIVE: To know the degree of BP control by clinical measurement. MATERIAL AND METHODS: During November 2019 demographic and clinical data, office attended systolic BP (SBP) and diastolic BP (DBP) measured with an automatic device with delayed reading and, if performed, data from ambulatory BP monitoring (ABPM) were collected. RESULTS: 102 patients (67 men) were included, with a mean age of 64.9 years, 30% diabetic and 34% with cardiovascular complications. 70% had a controlled hypertesion (<140/90 mmHg) by office BP, the mean SBP was 131 ± 16.5 mmHg and the DBP was 73 ± 9.5 mmHg. Old age and diabetes were associated with uncontrolled hypertension. Thirty three patients had ABPM data, which allowed them to be classified according to the 24-hour BP into: 30% true normotension, 9% white-coat hypertension, 15% sustained hypertension, and 45% masked hypertension. CONCLUSION: The use of automatic devices reduces the white-coat phenomenon, improving the % of patients with office BP controlled. However, this is not confirmed outside the clinic, showing the importance of ABPM in the evaluation of hypertension control. Office BP measurement is useful in patients initial assessment and also provides educational aspects, although the methodology must be optimized to define its clinical role.

[Hypertension in the elderly: What we need to know]. / Hipertensión del anciano: qué debemos conocer.

More than two thirds of people over 65 are hypertensive. Along with the high prevalence, hypertension is associated by comorbidities that originates a heterogeneous elderly population in relation to their autonomy and functional capacity. At this age, hypertension has special characteristics that make its management difficult, highlighting by isolated systolic hypertension due to the vascular stiffness typical of aging. Although decision-making is based on the clinical measurement of blood pressure, it is known that in the elderly pressure is subject to numerous influences: temporal (absence of night dipping), of the environment (exacerbation of the white coat phenomenon) and of the position (orthostatic hypotension). These circumstances must be taken into account when evaluating and deciding on therapy. At this age, there is sufficient evidence that treatment reduces both cardiovascular morbimortality and all-cause mortality.

¿Cómo influye el consumo de sal en la presión arterial? Mecanismos etiopatogénicos asociados / How does salt intake influence blood pressure? Associated aetiopathogenic mechanisms

Existen numerosas evidencias tanto epidemiológicas como experimentales que demuestran la existencia de una relación entre el consumo de sal y las cifras de presión arterial. Los individuos tienen distintos grados de susceptibilidad al efecto presor de la sal, fenómeno que se conoce como sensibilidad a la sal. El fenómeno del incremento o no modificación de las cifras de presión arterial al pasar de una dieta pobre en sal a otra rica ha llevado a acuñar los conceptos de sensibilidad o resistencia a la sal. Clásicamente se ha aceptado la teoría de Guyton del fenómeno de natriuresis por presión para explicar este efecto, así como, el papel fundamental que desempeñan las distintas proteínas transportadoras de sodio de los túbulos renales. En los últimos años, hay trabajos que cuestionan esta teoría y apuntan al posible papel del sistema inmune y de un tercer almacén de sodio en el organismo como factores etiopatogénicos

Abundant evidence from epidemiological and experimental studies has established a link between salt and blood pressure. However, there is heterogeneity in the blood pressure responses of humans to changes in sodium intake. Those individuals in whom a severe, abrupt change in salt intake causes the least change in arterial pressure and are termed salt-resistant, whereas in those in whom this leads to large changes in blood pressure, are called salt sensitive. Classically, Guyton's theory of the pressure-natriuresis phenomenon has been accepted to explain the pressor effect of salt, as well as the fundamental role played by the different protein sodium transporters of the renal tubules. In recent years, new theories have emerged pointing to the possible role of the immune system and the existence of a third sodium store in the body as aetiopathogenic factors

[How does salt intake influence blood pressure? Associated aetiopathogenic mechanisms]. / ¿Cómo influye el consumo de sal en la presión arterial? Mecanismos etiopatogénicos asociados.

Abundant evidence from epidemiological and experimental studies has established a link between salt and blood pressure. However, there is heterogeneity in the blood pressure responses of humans to changes in sodium intake. Those individuals in whom a severe, abrupt change in salt intake causes the least change in arterial pressure and are termed salt-resistant, whereas in those in whom this leads to large changes in blood pressure, are called salt sensitive. Classically, Guyton's theory of the pressure-natriuresis phenomenon has been accepted to explain the pressor effect of salt, as well as the fundamental role played by the different protein sodium transporters of the renal tubules. In recent years, new theories have emerged pointing to the possible role of the immune system and the existence of a third sodium store in the body as aetiopathogenic factors.

Hiperuricemia y riesgo cardiovascular: Mito o realidad / Hyperuricemia and cardiovascular risk: myth or fact?

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El péptido natriurético endotelial de tipo C mantiene la homeostasis vascular / No disponible

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La hipertensión acelera la progresión de la enfermedad de Alzheimer en un modelo de ratón de la enfermedad / No disponible

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El uso de nuevas técnicas para el diagnóstico de recidiva del feocromocitoma / The use of new techniques for diagnosis of relapse of pheochromocytoma

El feocromocitoma es un tumor secretor de catecolaminas que procede de las células cromafines de la médula suprarrenal y del tejido simpático y parasimpático extraadrenal. Para su diagnóstico se deben realizar pruebas hormonales complementadas con técnicas de imagen como la tomografía (TAC) y/o la resonancia magnética (RM). La confirmación de sulocalización así como la existencia de tumores múltiples requiere el uso de una prueba funcional, siendo de elección la gammagrafía con iodometilbencilguanidina (IMBG). Su sensibilidad disminuye en feocromocitomas de localización extra adrenal o malignos. Se presentan 2 casosen los que, a pesar de una alta sospecha diagnóstica de recidiva de feocromocitoma, la gammagrafría con IMBG fue negativa, siendo la tomografía por emisión de positrones (PET-CT) con18-fluorodesoxiglucosa (18F-FDG) fundamental para el diagnóstico en ambos casos. Además, se comenta la necesidad de hacer un estudio genético en algunos casos con feocromocitoma nosindrómico (AU)

Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffincells of the adrenal medulla and extra-adrenal sympathetic and parasympathetic tissue. Diagnosis should be made by hormonal tests and supplemented with imaging techniques such as tomography (CT) and/or magnetic resonance imaging (MR). To confirm its location and the existence of multiple tumors, it is necessary to perform a functional test, the iodomethyl-benzylguanidine (IMBG) scintigraphy being the test of choice. Its sensitivity decreases in extra-adrenal location pheochromocytomas or malignant tumors. Two cases are reported in which, despite high clinical suspicion of recurrence of pheochromocytoma, the IMBG scintigraphy was negative. The positron emission tomography (PET-CT) using 18-fluorodeoxyglucose(18F-FDG) was essential for the diagnosis in both cases. In addition, the need for a genetic study in some cases of non-syndromic pheochromocytoma is discussed (AU)

Molecular biology of water and salt regulation in the kidney.

The kidney plays a central role in the regulation of the salt and water balance, which depends upon an array of solute and water transporters in the renal tubules and upon vascular elements in the various regions of the kidney. Many recent studies have improved our understanding of this process. In this review, we summarize the current data on the molecules involved in sodium and water transport in the renal tubules, focusing in particular on aquaporins and renal sodium transporters and channels.

Aportaciones de la proteómica al estudio de las enfermedades cardiovasculares / Contributions of proteomics to the study of cardiovascular diseases

El gran desarrollo tecnológico en la era de la posgenómica está condicionando un cambio de rumbo de la investigación pasando de una investigación de moléculas individuales(«reduccionista») a una investigación de conjunto e integración en sistemas dinámicos, lo que actualmente se denomina biología de sistemas. Una de las áreas que está sufriendo más cambios ha sido la investigación de las proteínas, lo que ha condicionado la aparición de una nueva disciplina denominada proteómica. En este artículo de revisión se pretende, de una manera sencilla, introducir a los clínicos en la proteómica y en las nuevas tecnologías que se utilizan para el estudio de las proteínas y revisar los trabajos más relevantes que han aplicado esta tecnología al estudio de las enfermedades cardiovasculares (AU)

The important technological development in the post-genomic era is conditioning a shift in research from the study of individual molecules (¨reductionist¨) to a study of the combination and integration of information into dynamic systems. This is currently called systems biology. One area that has undergone more changes has been the investigation of proteins, which has conditioned the emergence of a new discipline called proteomics. This review article is intended to introduce proteomics and the new technologies used for protein studies to clinicians is an easy way. In addition, the article reviews the most relevant studies that have applied this technology to the investigation of cardiovascular diseases (AU)

[Relationship between renal size and blood pressure profile in patients with autosomal dominant polycystic kidney disease without renal failure]. / Relación entre el tamaño renal y el perfil de presión arterial en pacientes con poliquistosis renal autosómica dominante sin insuficiencia renal.

BACKGROUND: Enlargement of renal size plays an important role in the development of hypertension in patients with autosomic dominant polycystic kidney disease (ADPKD) and normal renal function. METHODS: A 24h blood pressure monitoring (ABPM) and a renal echography have been performed in 37 patients with ADPKD and estimated glomerular filtration rate > 60 ml/min/1.73 m(2) to study the relationship between renal size and an altered blood pressure profile in prehypertension stages. RESULTS: 13 patients had normal blood pressure, 11 were diagnosed of masked hypertension, 4 had white coat hypertension and 9 had hypertension. We have found in the normotensive group with a dipper blood pressure profile a positive and statistically significant relationship between renal size and diastolic blood pressure variability. CONCLUSIONS: ABPM helps to make an early diagnosis of hypertension and to identify those patients with masked hypertension. This study suggests a relationship between renal size and a blood pressure profile linked to a major cardiovascular risk in normotensive patients with ADPKD.

Relación entre el tamaño renal y el perfil de presión arterial en pacientes con poliquistosis renal autosómica dominante sin insuficiencia renal / Relationship between kidney size and blood pressure profile in patients with autosomal dominant polycystic kidney disease without renal failure

Antecedentes: El aumento del tamaño renal desempeña un papel importante en el desarrollo de la hipertensión arterial (HTA) en pacientes con poliquistosis renal autosómica dominante (PQRAD) con función renal normal. Material y métodos: Se han practicado a 37 pacientes con PQRAD, filtrado glomerular estimado (FGe) por MDRD>60 ml/min/1,73 m2y supuestamente normotensos, una monitorización de la presión arterial (MAPA) y una ecografía renovesical para investigar la posible relación entre el aumento del tamaño renal y un perfil patológico de presión arterial (PA) en estadios de prehipertensión. Resultados: 13 pacientes resultaron ser normotensos, 11 presentaron HTA enmascarada, cuatro tuvieron HTA de bata blanca y nueve, HTA verdadera. Se ha observado en los pacientes normotensos con patrón reductor de la PA una correlación positiva y estadísticamente significativa entre el tamaño renal y la variabilidad de la presión arterial diastólica (PAD). Conclusiones: La MAPA permite realizar un diagnóstico precoz de la HTA e identificar apacientes con hipertensión enmascarada. Este trabajo sugiere que en pacientes normotensos con PQRAD existe una posible relación entre el tamaño renal y un perfil de PA con mayor riesgo cardiovascular (AU)

Background: Enlargement of renal size plays an important role in the development of hypertension in patients with autosomal dominant polycystic kidney disease (ADPKD)and normal renal function. Methods: A 24h blood pressure monitoring (ABPM) and a renal ecography have been performed in 37 patients with ADPKD and estimated glomerular filtration rate >60 ml/min/1,73 m2to study the relationship between renal size and an altered blood pressure profile in prehypertension stages. Results: 13 patients had normal blood pressure, 11 were diagnosed of masked hypertension, 4 had white coat hypertension and 9 had hypertension. We have found in the normotensive group with a dipper blood pressure profile a positive and statistically significant relationship between renal size and diastolic blood pressure variability. Conclusions: ABPM helps to make an early diagnosis of hypertension and to identify those patients with masked hypertension. This study suggests a relationship between renal size and a blood pressure profile linked to a major cardiovasular risk in normotensive patients with ADPKD (AU)

Complicaciones de aterosclerosis de grandes vasos / Complications of large vessel atherosclerosis

La enfermedad renal ateroembólica es consecuencia del desprendimiento y migración a vasos distales de microémbolos de colesterol, procedentes de placas de ateroma de grandes arterias. Estos émbolos pueden ocluir pequeños vasos en el riñón, retina, cerebro, páncreas, músculos y piel. Se produce en pacientes con arterioesclerosis tras procesos endovasculares o bien se puede producir espontáneamente. Por ello ante un deterior de función renal inexplicable, en paciente con signos de arterioesclerosis, se debe sospechar siempre una enfermedad ateroembólica y buscar manifestaciones extrarrenales. En estos casos, puede ser necesaria la confirmación histológica para el diagnóstico definitivo. No existe tratamiento específico, debiendo tomar algunas medidas como, suspender los anticoagulantes, las manipulaciones aórticas y reducir la PA. De ello dependerá la evolución, ya que ésta puede ser muy variable siendo, desde formas leves, hasta potencialmente mortales. Por otro lado es conveniente remarcar; que a pesar del control estricto de los factores de riesgo vascular, la enfermedad aterosclerótica es una enfermedad progresiva, como se desprende del caso que presentamos y aconsejamos en pacientes de este tipo, con alto riesgo vascular, la toma periódica de la PA en ambas extremidades (AU)

Atheroembolic renal disease is a consequence of the detachment and migration of microemboli distal vessels of cholesterol from atherosclerotic plaques of large arteries. These emboli can occlude small vessels in the kidney, retina, brain, pancreas, muscles and skin. It occurs in patients with atherosclerosis after endovascular procedures or it may occur spontaneously. Therefore, before an unexplained deterioration of renal function, in patients with signs of atherosclerosis, an atherosclerotic disease should always be suspected and seek for extra renal manifestations. In these cases, histological confirmation may be required for definitive diagnosis. There is non specific treatment and certain measures should be taken such as suspending anticoagulants, aortic manipulation and reducing the blood pressure. The evolution will depend on this, as it can vary from being mild to life-threatening forms. On the other band, it is advisable to note, that in despite the strict control of vascular risk factors, atherosclerotic disease is a progressive disease, as shown in the case reported, and in such patients, with high vascular risk, we advise monitoring their BP regularly in both extremities (AU)

Aplicación práctica de la evaluación de la sensibilidad a la sal / Application of the assessment of salt sensitivity

Hay numerosas evidencias tanto epidemiológicas como experimentales que demuestranla relación entre el consumo de sal y las cifras de presión arterial (PA). Los individuostienen distintos grados de susceptibilidad al efecto presor de la sal, fenómeno que seconoce como sensibilidad a la sal. El fenómeno de que las cifras de PA se incrementen ono se modifi quen al pasar de una dieta pobre en sal a otra rica en sal ha llevado a acuñarlos conceptos de sensibilidad o resistencia a la sal. La sensibilidad a la sal aumenta conla edad, también se observa con más frecuencia en pacientes de raza negra, diabéticos ynefrópatas. Hay distintos métodos para evaluar la respuesta de la PA a los cambios en laingesta de sal. Dada la complejidad de los protocolos, la evaluación de la sensibilidad ala sal se usa con propósitos de investigación y es ocasional su uso en la práctica clínica(AU)

Abundant evidence from epidemiological and experimental studies has established a linkbetween salt and blood pressure values. Individuals have different grades of susceptibilityto the pressure effect of salt, a phenomenon known as salt sensitivity. The phenomenonof increase or no change in BP blood pressure values when changing from a low-salt dietto a high-salt diet has resulted in a concept called salt sensitivity or resistance. Saltsensitivity increases with age, black race, diabetes mellitus and renal diseases. A varietyof different techniques have been used to assess blood pressure response to changes insalt intake in humans. However, due to the complexity of the procedure they are mainlyused for research and occasionally for clinical practice(AU)

Preservation of renal function in a patient with Fabry nephropathy on enzyme replacement therapy.

Fabry disease is an X-linked recessive inborn error of glycosphingolipid metabolism caused by the deficient activity of the lysosomal enzyme, alpha-galactosidase A. Enzyme replacement therapy (ERT) for this disorder has been available in Europe since 2001. However, its effect on advanced renal failure remains controversial. We report the case of a patient whose decline in renal function was reduced by the administration of ERT (agalsidase-alpha). This reduction was more pronounced after doubling the dose of the enzyme. The rate of deterioration of eGFR went from 6.3 ml/min/year prior to the start of ERT (0.2 mg/kg) to 2 ml/min/year (0.4 mg/kg). To our knowledge, this is the first reported case of a patient with moderately impaired renal function treated with high doses of ERT and follow-up of 6 years. The data shown here suggest that ERT may have a very positive impact on renal function even in advanced stages. The role of proteinuria and its control seem to have a clear responsibility for this favorable outcome.

Diagnostic procedures and rationale for specific therapies in chronic kidney disease-mineral and bone disorder.

Chronic kidney disease (CKD) is associated with increased mortality. Non-traditional risk factors, such as mineral metabolism disturbances, seem to contribute to the unexpected high mortality rate. A chronic kidney disease-mineral bone disorder (CKD-MBD) has recently been defined as a systemic disorder manifested by one or a combination of abnormalities in bone biopsy, laboratory parameters, and/or vascular or other soft tissue calcifications. Recent research developments and new available treatments have all contributed to move the former treatment paradigm beyond the control of PTH. Thus, despite much of the advice given by different societies being just opinion-based evidence, the effect of different drugs on laboratory parameters, vascular calcification (VC) or survival may steer the choice of specific treatments. Aluminum and calcium-based phosphorus binders have been associated either with metal toxicity or progression of VC. Sevelamer hydrochloride has been related to an attenuation of the progression of VC and it has also been associated with improved survival at least in certain subgroups of dialysis patients. Lanthanum carbonate decreases phosphorus levels but its impact on surrogate or hard outcomes is not known. Selective vitamin D-receptor activators may have differential effects on VC, are associated with a survival advantage and thereby may have a best-fitted profile for CKD patients. On the other hand, calcimimetics markedly help to achieve current guidelines and ongoing clinical trials are evaluating hard outcomes. It is likely that a regimen combining several drugs might improve individual results. However, the utility of any new approach to CKD-MBD will need to be evaluated in prospective trials including thorough pharmacoeconomic analysis.

Mieloma múltiple y fracaso renal agudo / Multiple mieloma and acute renal failure

El mieloma múltiple es una proliferación neoplásica de células plasmáticas que producen una inmunoglobulina de forma monoclonal. Representa el 1% de todas las enfermedades malignas y el 10% de las enfermedades malignas hematológicas siendo más frecuente en hombres con una edad media al diagnóstico de 66 años. La afectación renal en el mieloma múltiple es frecuente y en el momento de presentación, la alteración de la función renal puede ser presente en el 50% de los casos. Se presenta el caso de uan paciente de 71 años que fue diagnosticada de mieloma múltiple a raíz de un fracaso renal agudo. Se realizó una biopsia renal objetivándose imágenes compatibles con nefropatía por mieloma. Tras llegar al diagnóstico de mieloma múltiple a través de biopsia de médula ósea se realizó tratamiento quimioterápico con vincristina, adriamicina y dexametasona sin presentar respuesta de su enfermedad de base

The múltiple myeloma is a neoplasis proliferation of plasma cells that produce an immunoglobulin of monoclonal form. It represents the 1% of all the malignant diseases and 10% of the haematological malignant diseases, being more frequent in men with a middle ages to the diagnosis of 66 years. The renal affectation in the multiple myeloma is frequent and in the moment of presentation, the renal function alteration can be present in the 50% of cases. The case appears of patient of 71 years who was diagnosed of multiple myeloma immediately after a renal sharp failure. It was realized a renal biopsy with the vision of images compatible with nephropathy by myeloma. After coming to the diagnosis of multiple myeloma through bone marrow´s biopsy, it was made a chemotherapeutic treatment with vincristina, adriamicina and dexametasona without to show response of his base disease