Características de la población general incluida en el estudio RICARTO (RIesgo CARdiovascular y eventos cardiovasculares en la población general del área sanitaria de TOledo): resultados con los primeros 1.500 individuos incluidos en el estudio / Characteristics and cardiovascular events in a general population included in the RICARTO (RIesgo CARdiovascular TOledo) study: data from the first 1.500 individuals included in the study

Introducción. El objetivo fue investigar prevalencias de factores de riesgo cardiovascular (FRCV), lesión de órgano diana (LOD) y enfermedad cardiovascular (ECV) en población general del Área Sanitaria de Toledo para determinar el riesgo cardiovascular (RCV). Material y métodos. Estudio epidemiológico observacional que analizó una muestra de población general ≥18años seleccionada de la base de datos de tarjeta sanitaria por muestreo aleatorio sistemático estratificado por sexo y grupos de edad. Se realizaron anamnesis, exploración clínica y pruebas complementarias, congelándose a −85°C alícuotas de sangre total y suero para valorar posibles estudios genéticos. Se realizó análisis estadístico estándar. El RCV se estimó con las escalas del Proyecto SCORE calibrada para población española y del Framingham Heart Study. Resultados. Se incluyeron a 1.500 individuos (edad media 49,1±15,8años; 55,6% mujeres). Prevalencias: dislipemia 56,9% (intervalo de confianza al 95% [IC95%]: 54,3-59,4), hipertensión arterial 33,0% (IC95%: 30,6-35,4), diabetes mellitus 8,6% (IC95%: 7,17-10,1), tabaquismo 24,2% (IC95%: 22,0-26,4), obesidad 25,3% (IC95%:23,1-27,5) y sedentarismo 39,4% (IC95%: 36,9-41,8). El 21,1% no mostró ningún FRCV y el 18,6% presentó de 3 a 5. LOD: hipertrofia ventricular izquierda electrocardiográfica 4,3%, arteriopatía periférica con eco-doppler10,1% y con dispositivo oscilométrico 15,3%, microalbuminuria 4,3%, enfermedad renal oculta 3,2% y nefropatía 3,8% (CKD-EPI). El 9,2% padecía alguna ECV. El 44,6% mostró RCV (SCORE) bajo. Conclusiones. De cada 10 personas, 6 presentan dislipemia, 4 sedentarismo, 3 hipertensión, 2 tabaquismo, 2 obesidad, y casi una diabetes. Más de la mitad de los individuos muestran RCV moderado-alto-muy alto y las prevalencias de LOD y ECV son importantes

Introduction. The aim of this study was to assess cardiovascular risk (CVR) by investigating the prevalence of CVR factors (CVRF), target organ damage (TOD), and cardiovascular disease (CVD) in general population of the health area of Toledo, Spain. Material and methods. Epidemiological and observational study that analysed a sample from the general population aged 18years or older, randomly selected from a database of health cards stratified by age and gender. Clinical history, physical examination, and complementary tests were performed. Total blood and serum samples were frozen at −85°C to evaluate genetic studies in the future. Standard statistical analysis was performed. CVR was assessed by the SCORE scale calibrated for the Spanish population, and the Framingham Heart Study scale. Results. A total of 1,500 individuals (mean age 49.1±15.8years, 55.6% women) were included. Prevalences: dyslipidaemia 56.9% (95% confidence interval [95% CI]: 54.3-59.4), hypertension 33.0% (95%CI: 30.6-35.4), diabetes mellitus 8.6% (95%CI: 7.17-10.1), smoking 24.2% (95%CI; 122.0-26.4), obesity 25.3% (95%CI; 23.1-27.5), and sedentary life-style 39.4% (95%CI; 36.9-41.8). No CVRF was reported in 21.1% of cases, and 18.6% had 3-5 CVRF. TOD: electrocardiographic left ventricular hypertrophy, 4.3%, peripheral artery disease, 10.1% (Doppler ultrasound), and 15.3% (oscillometric device), microalbuminuria, 4.3%, sub-clinical renal disease, 3.2%, and nephropathy in 3.8% (CKD-EPI). At least one CVD was reported in 9.2% of cases. A low CVR (SCORE) was present in 44.6% of individuals. Conclusions. Dyslipidaemia was found in 60% of individuals, 40% had a sedentary life-style, 30% with hypertension, 20% smoked, 20% obesity, and almost 10% with diabetes. More than a half of individuals have a moderate-high-very high risk. The prevalence of TOD and CVD are significant

Justificación, objetivos y diseño metodológico del estudio RICARTO (RIesgo CARdiovascular y eventos cardiovasculares en la población general del área sanitaria de TOledo) / Cardiovascular risk and cardiovascular events in the general population of the sanitary area of Toledo. RICARTO Study

Introducción. El objetivo principal es conocer en la población del Área Sanitaria de Toledo las prevalencias de factores de riesgo cardiovascular (FRCV), lesión de órgano diana (LOD) y enfermedad cardiovascular (ECV), así como los hábitos de vida (ejercicio físico y consumo de alcohol y de dieta mediterránea), para determinar el riesgo cardiovascular (RCV). Material y métodos. Estudio epidemiológico observacional que analizará una muestra de población general≥ 18 años seleccionada de la base de datos de tarjeta sanitaria por muestreo aleatorio sistemático estratificado por sexo y grupos de edad. Se realizarán anamnesis, exploración clínica y pruebas complementarias, y se congelarán a -85°C alícuotas de sangre total y suero para valorar futuros estudios genéticos. El RCV se estimará con las escalas del proyecto SCORE calibrada para población española y del Framingham Heart Study. Alcanzado el tamaño muestral estimado y transcurridos al menos 5 años de la inclusión, se realizará seguimiento de la muestra final de sujetos, analizando la evolución de FRCV, LOD, ECV y del control de FRCV, y los eventos sucedidos mortales y no mortales. Discusión. El estudio RICARTO pretende conocer las prevalencias de los principales FRCV, LOD y ECV, para determinar el RCV de la población general del Área Sanitaria de Toledo, y realizar un seguimiento de la muestra final de individuos cuando hayan transcurrido al menos 5 años de la inclusión para analizar la incidencia de eventos cardiovasculares y la evolución temporal de los estilos de vida, las prevalencias de FRCV, LOD y ECV

Introduction. The main aim of this study is to ascertain the prevalence of cardiovascular risk factors (CVRF), target organ damage (TOD), cardiovascular disease (CVD), as well as life habits (physical exercise, alcohol consumption, and Mediterranean diet) in the population of a Health Area in Toledo, Spain, to assess cardiovascular risk (CVR). Material and methods. Epidemiological and observational study that will analyse a sample from the general population aged 18 years or older, randomly selected from a database of health cards, and stratified by age and gender. Clinical history, physical examination, and complementary tests will be performed. Aliquots of whole blood and serum samples will be stored at a temperature of -85°C to evaluate future genetic studies. CVR will be estimated by using SCORE project scales calibrated for Spanish population and the Framingham Heart Study scale. When the estimated sample size has been achieved and after a minimum follow-up of 5 years, a final visit will performed in which CVRF, TOD, CVD, CVRF control, and fatal and non-fatal outcomes will be evaluated. Discussion. The RICARTO study is aimed to assess the prevalence of the main CVRF, TOD and CVD in order to determine the CVR in the general population of a health area of Toledo. An analysis will be repeated on the final sample after at least 5 years of follow-up to ascertain the incidence of CV outcomes and the temporal trends of life style, as well as the prevalence of CVRF, TOD, and CVD

[Cardiovascular risk and cardiovascular events in the general population of the sanitary area of Toledo. RICARTO Study]. / Justificación, objetivos y diseño metodológico del estudio RICARTO (RIesgo CARdiovascular y eventos cardiovasculares en la población general del área sanitaria de TOledo).

INTRODUCTION: The main aim of this study is to ascertain the prevalence of cardiovascular risk factors (CVRF), target organ damage (TOD), cardiovascular disease (CVD), as well as life habits (physical exercise, alcohol consumption, and Mediterranean diet) in the population of a Health Area in Toledo, Spain, to assess cardiovascular risk (CVR). MATERIAL AND METHODS: Epidemiological and observational study that will analyse a sample from the general population aged 18 years or older, randomly selected from a database of health cards, and stratified by age and gender. Clinical history, physical examination, and complementary tests will be performed. Aliquots of whole blood and serum samples will be stored at a temperature of-85°C to evaluate future genetic studies. CVR will be estimated by using SCORE project scales calibrated for Spanish population and the Framingham Heart Study scale. When the estimated sample size has been achieved and after a minimum follow-up of 5 years, a final visit will performed in which CVRF, TOD, CVD, CVRF control, and fatal and non-fatal outcomes will be evaluated. DISCUSSION: The RICARTO study is aimed to assess the prevalence of the main CVRF, TOD and CVD in order to determine the CVR in the general population of a health area of Toledo. An analysis will be repeated on the final sample after at least 5 years of follow-up to ascertain the incidence of CV outcomes and the temporal trends of life style, as well as the prevalence of CVRF, TOD, and CVD.

[Characteristics and cardiovascular events in a general population included in the RICARTO (RIesgo CARdiovascular TOledo) study: Data from the first 1,500 individuals included in the study]. / Características de la población general incluida en el estudio RICARTO (RIesgo CARdiovascular y eventos cardiovasculares en la población general del área sanitaria de TOledo): resultados con los primeros 1.500 individuos incluidos en el estudio.

INTRODUCTION: The aim of this study was to assess cardiovascular risk (CVR) by investigating the prevalence of CVR factors (CVRF), target organ damage (TOD), and cardiovascular disease (CVD) in general population of the health area of Toledo, Spain. MATERIAL AND METHODS: Epidemiological and observational study that analysed a sample from the general population aged 18years or older, randomly selected from a database of health cards stratified by age and gender. Clinical history, physical examination, and complementary tests were performed. Total blood and serum samples were frozen at -85°C to evaluate genetic studies in the future. Standard statistical analysis was performed. CVR was assessed by the SCORE scale calibrated for the Spanish population, and the Framingham Heart Study scale. RESULTS: A total of 1,500 individuals (mean age 49.1±15.8years, 55.6% women) were included. Prevalences: dyslipidaemia 56.9% (95% confidence interval [95% CI]: 54.3-59.4), hypertension 33.0% (95%CI: 30.6-35.4), diabetes mellitus 8.6% (95%CI: 7.17-10.1), smoking 24.2% (95%CI; 122.0-26.4), obesity 25.3% (95%CI; 23.1-27.5), and sedentary life-style 39.4% (95%CI; 36.9-41.8). No CVRF was reported in 21.1% of cases, and 18.6% had 3-5 CVRF. TOD: electrocardiographic left ventricular hypertrophy, 4.3%, peripheral artery disease, 10.1% (Doppler ultrasound), and 15.3% (oscillometric device), microalbuminuria, 4.3%, sub-clinical renal disease, 3.2%, and nephropathy in 3.8% (CKD-EPI). At least one CVD was reported in 9.2% of cases. A low CVR (SCORE) was present in 44.6% of individuals. CONCLUSIONS: Dyslipidaemia was found in 60% of individuals, 40% had a sedentary life-style, 30% with hypertension, 20% smoked, 20% obesity, and almost 10% with diabetes. More than a half of individuals have a moderate-high-very high risk. The prevalence of TOD and CVD are significant.

Validez y fiabilidad de un indicador sintético de calidad de la atención hospitalaria / Validity and reliability of a synthetic hospital health care quality indicator

Objetivo. El benchmarking entre diferentes organizaciones sanitarias es una herramienta útil para la mejora de la calidad, pero requiere contar con indicadores válidos y fiables para que las comparaciones se basen en datos objetivos. El objetivo de este trabajo es contrastar la validez y la fiabilidad de un indicador sintético de calidad de la atención hospitalaria. Material y métodos. Estudio transversal, sobre los indicadores del Plan de Calidad de 10 hospitales, bajo el modelo de la European Fondation of Quality Management (EFQM) en un periodo de 5 años. Se contrasta la fiabilidad, mediante el coeficiente alfa de Cronbach. La validez se contrasta mediante un análisis de conglomerados (dendograma), explorando asociaciones entre resultados de indicadores diferentes, y mediante un análisis exploratorio de las correlaciones entre los indicadores de proceso y los indicadores de resultados propuestos por la Agencia Norteamericana de Investigación en Calidad (AHRQ). Resultados. Se ha encontrado una fiabilidad «aceptable» (α=0,759). No se han hallado conglomerados que respondan a la agrupación de criterios del modelo EFQM ni correlaciones significativas con los indicadores de resultados. Conclusiones. Se propone continuar elaborando indicadores que se muestren empíricamente válidos para integrarse en indicadores sintéticos, de forma que pueda compararse la eficiencia de la gestión sanitaria en todos los hospitales(AU)

Objective. Benchmarking between different health organisations is a useful tool for improving quality, but it requires using valid and reliable indicators so that comparisons may be based on objective data. The aim of this work is to verify the validity and reliability of a synthetic hospital health care quality indicator. Material and methods. A cross-sectional study was conducted over a five-year period on the Quality Plan indicators of 10 hospitals, under the model of the European Foundation of Quality Management (EFQM). Reliability was checked using the Cronbach's alpha coefficient. The validity was determined using a cluster analyses (dendrogram), examining relationships between different indicator results, and by means of an exploratory analysis of the correlations between the process indicators and results indicators proposed by the US Agency for Healthcare Research and Quality (AHRQ). Results. An «acceptable» reliability was found (α=0.759). No clusters were found that corresponded to the set of criteria of the EFQM model, or any significant correlations with the results indicators. Conclusions. It is proposed to continue devising indicators that could empirically be shown to be valid in order to be incorporated into synthetic indicators, in such a way that the efficiency of health care management in all hospitals may be compared(AU)

[Validity and reliability of a synthetic hospital health care quality indicator]. / Validez y fiabilidad de un indicador sintético de calidad de la atención hospitalaria.

OBJECTIVE: Benchmarking between different health organisations is a useful tool for improving quality, but it requires using valid and reliable indicators so that comparisons may be based on objective data. The aim of this work is to verify the validity and reliability of a synthetic hospital health care quality indicator. MATERIAL AND METHODS: A cross-sectional study was conducted over a five-year period on the Quality Plan indicators of 10 hospitals, under the model of the European Foundation of Quality Management (EFQM). Reliability was checked using the Cronbach's alpha coefficient. The validity was determined using a cluster analyses (dendrogram), examining relationships between different indicator results, and by means of an exploratory analysis of the correlations between the process indicators and results indicators proposed by the US Agency for Healthcare Research and Quality (AHRQ). RESULTS: An «acceptable¼ reliability was found (α=0.759). No clusters were found that corresponded to the set of criteria of the EFQM model, or any significant correlations with the results indicators. CONCLUSIONS: It is proposed to continue devising indicators that could empirically be shown to be valid in order to be incorporated into synthetic indicators, in such a way that the efficiency of health care management in all hospitals may be compared.

[The role of calcium, calcitriol and their receptors in parathyroid regulation]. / Papel de calcio, calcitriol y sus receptores en la regulación de la paratiroides.

The mechanism of regulation of Parathyroid hormone (PTH) is complex, and diverse factors are involved: the fundamental ones are calcium, calcitriol and phosphorus. Calcium and calcitriol's mechanism of action takes place through its specific receptors, the calcium-sensing receptor (CaR) and the Vitamin D Receptor (VDR). These two factors have an effect not only on its specific receptors, but also they can modify the other receptor in a positive manner, promoting its actions and demonstrating a cooperative effect between the two. Along with calcium and calcitriol, drugs used in the treatment of Chronic Kidney Disease Mineral Bone Disorders (CKD-MBD) also act directly or indirectly on CaR and VDR and therefore are also responsible for the regulation of the parathyroid gland.

Papel de calcio, calcitriol y sus receptores en la regulación de la paratiroides / No disponible

El mecanismo de regulación de los niveles de Parathormona (PTH) es complejo, y en él intervienen diversos factores: los fundamentales son el calcio, el calcitriol y el fósforo. El mecanismo de acción de calcio y calcitriol tiene lugar a través de sus receptores específicos, el Receptor-sensor de Calcio (CaR) y el Receptor de Vitamina D (VDR). Estos dos factores tienen efecto no sólo sobre sus receptores específicos sino que pueden modificar en sentido positivo al otro receptor, potenciando sus acciones y demostrando un efecto cooperativo entre ambos. Además de calcio y calcitriol, los fármacos que se utilizan en el tratamiento de las alteraciones del metabolismo óseo y mineral de la Enfermedad Renal Crónica (ERC) también actúan directa o indirectamente sobre CaR y VDR y, por tanto, también son responsables de la regulación de la paratiroides (AU)

No disponible

Effects of estradiol, calcitriol and both treatments combined on bone histomorphometry in rats with chronic kidney disease and ovariectomy.

BACKGROUND: The aim of this experimental study was to analyze the histomorphometric changes observed when using different doses of estradiol, calcitriol and both treatments combined, in rats with both chronic kidney disease (CKD) and ovariectomy (OVX). METHODS: Six groups of rats with CKD+OVX were treated for 8 weeks with placebo, with different doses of 17beta-estradiol (E2), with calcitriol or with both treatments combined (E2+calcitriol). Histomorphometric studies were carried out at the proximal tibia segment. RESULTS: All groups that received active treatments showed a trabecular bone volume similar to those of rats with normal ovarian function. Treatment with E2 was effective, E2-10 diminished osteoid and eroded surfaces, and E2-30 was able to achieve a bone remodeling similar to that of the normal group. Calcitriol proved to have a positive effect on bone microarchitecture, achieving normal trabecular connectivity. The combined treatment with E2-30+calcitriol was the most effective treatment as it was not only capable of achieving normal trabecular remodeling and connectivity, but also normal trabecular bone volume. CONCLUSIONS: E2 and calcitriol seem to have independent effects on cancellous bone turnover in rats with CKD+OVX. In rats with chronic kidney disease and ovariectomy, these two agents are able to produce additive effects on bone and offer additional advantages as opposed to the use of both drugs independently.

Mecanismos moleculares de toxicidad en la sobrecarga alumínica / Molecular mechanisms of toxicity in aluminium overload

Anteriormente se había observado que el aluminio era capaz de inhibir la síntesis y la secreción de hormona paratiroidea, si bien los mecanismos moleculares subyacentes se desconocían. Estudios recientes han demostrado que dicha inhibición tiene lugar a través de un mecanismo post-transcripcional. Además, el aluminio disminuye la proliferación de las células de la glándula paratiroides de un modo similar al calcio, el principal regulador de la función paratiroidea. Por último, el aluminio es también capaz de activar el receptor-sensor de calcio a concentraciones micromolares, lo que demuestra que éste es el mecanismo por el que las glándulas paratiroides respondían al metal. En conjunto, estos resultados demuestran por primera vez que las acciones del aluminio sobre la función paratiroidea tienen lugar a través de un mecanismo similar al del calcio. Además, dicho efecto es consecuencia de la baja especificidad del receptor-sensor del calcio

Aluminum (Al) is able to inhibit parathyroid hormone (PTH) synthesis and secretion, although the subjacent molecular mechanisms are unknown. Recent studies have shown that this inhibition occurs through a post-transcriptional mechanism. Similarly to calcium, the main regulator of parathyroid function, Al also decreases parathyroid cell proliferation. Finally, Al is also able to activate the calcium-sensing receptor (CaR) at the micromolar level, thus demonstrating that this is the mechanism by which parathyroid glands sense the metal. In summary these results show for the firs time that Al-induced impairment of parathyroid function is a calcium-like mechanism. In addition, this effect is the consequence of a low specificity of the CaR

[Erythropoietin: a study of its use in oncohematology]. / Eritropoyetina: estudio de utilización en oncohematología.

OBJECTIVE: To assess the effectiveness of erythropoietin (EPO) in a Clinical Oncohematology Unit within a general hospital, and to propose a therapeutic algorithm with EPO based on recommendations by ASCO. MATERIAL AND METHODS: A descriptive, retrospective study was carried out on patients who required support treatment with EPO while in the Oncohematology Unit during the year 2001. Data were collected by reviewing patient medical records. An effective treatment was defined as an increase in baseline hemoglobin (Hb) equal to or higher than 2 g/dL over 4-8 weeks, with no transfusion requirements or decreased transfusion needs. Baseline Hb values, their distribution per diagnosis, and the involvement of platinum-containing chemotherapy regimens were analyzed. RESULTS: Of the 353 patients in chemotherapy, 87% corresponded to oncologic diagnoses while the rest had hematological neoplasms. A total of 54 patients were assessed, with 83% of these corresponding to the oncologic area. Oncologic diagnoses that most required the use of EPO included: head-neck 53%, genitourinary 39%, and lung 39%. Overall effectiveness was 57% (60% in oncology and 44% in hematology). The Hb value leading to initial prescription (baseline Hb) was always below 10 g/dL for the hematology area, whereas most oncology patients exhibited higher levels at therapy onset. CONCLUSIONS: 1. Its percentage of failure: 40% for oncology and 56% for hematology patients, together with its high cost, shows that a further search for predictive factors is warranted in order to more precisely select individuals who may benefit from this therapy. 2. The percentage of oncology patients with baseline Hb <10 is only 29%. Baseline Hb values for treatment onset and peak Hb values for therapy discontinuation should be agreed upon. Treatment initiation when Hb values fall below 10 g/dL would be a reasonable option, and a decision to use EPO above 10 g/dL should be made in patients with less severe anemia (10-12 g/dL) only if clinical circumstances render it advisable. 3. Use protocols must include clear concept definitions for treatment, and for primary and secondary prophylaxis, which will help in the establishment of therapeutic algorithms.

[Regulation of the calcium-sensing receptor. Influence of secondary hyperparathyroidism]. / Regulación del receptor sensor de calcio. Influencia del hiperparatiroidismo secundario.

The parathyroid glands have a great sensitivity to small changes in the extracellular ionic calcium. The calcium-sensing receptor (CaR) is a G protein-coupled receptor that responds to extracellular ionic calcium changes activating several intracellular signalling systems (phospholipases C, A2 and D) finally inhibiting the PTH secretion. In addition to calcium, there are some other agonists and modulators such as the Mg2+, spermine, amyloid beta-peptides, a variety of aminoacids, especially aromatic aminoacids and ionic strength. In the uraemia, the sensitivity of the parathyroid glands to calcium is altered and higher values of calcium are necessary to suppress the PTH. In the secondary hyperparathyroidism the CaR expression is reduced. It has been found a negative correlation between cellular proliferation and the expression of the CaR in hyperplasic glands. Despite it is a calcium receptor, the expression of the CaR does not seem to be regulated by calcium and there is some controversy about the role of calcitriol regulating its expression. On the other hand, the phosphorous induces hyperplasia of the parathyroid gland increasing the cellular proliferation and a decrease of the CaR expression.

[Effect of desferrioxamine and deferiprone on osteocalcin secretion in osteoblast-type cells]. / Efecto de la desferrioxamina y de la deferiprona sobre la secreción de osteocalcina en células tipo osteoblasto.

Desferrioxamine and deferiprone are both metal-chelating drugs often used in aluminum-overloaded dialysis patients. In these patients, desferrioxamine produces an improvement on bone mineralisation without a relevant decrease in bone aluminum. Thus, desferrioxamine might have a direct effect on bone cells. The aim of this study was to assess the effect of desferrioxamine and deferiprone on 1,25(OH)2D3-stimulated osteocalcin secretion in osteoblast--like cells. The study was carried out in MG-63 cell cultures. Cells were seeded at a density of 15,000 cel/cm2 and grown to confluence for 72 hours in DMEM supplemented with 10% FCS. The medium was then replaced by another medium containing 1% BSA, 10(-9) M 1,25(OH)2D3 and desferrioxamine 5, 10, 20, 40, 60, 80 microM or deferiprone 15, 30, 60, 120, 180, 240 microM. Tris-HCl at pH 7.4 was used as control. After 48 hours, supernatants were collected for the measurement of secreted osteocalcin. Desferrioxamine and deferiprone, at high doses (desferrioxamine: 60 microM, 80 microM; deferiprone: 180 microM, 240 microM), inhibited the 1,25(OH)2D3-induced osteocalcin secretion. On the contrary, at lower doses (desferrioxamine 5 microM; deferiprone 15 microM) stimulated the secretion. In summary, these results suggest that desferrioxamine and deferiprone exert a direct effect on bone cell metabolism that might be independent from their metal-chelating properties.

[Biochemical and histological spectrum of renal osteodystrophy in Argentina]. / Espectro bioquímico e histológico de la osteodistrofia renal en Argentina.

Between 1994-2001 we have performed 57 bone biopsies for diagnostic purposes in symptomatic CRF patients. We analyzed here 52 samples where the material was optimal for study, and divided them into 2 periods according to when the biopsy was performed: 1994-1996 and 1997-2001, to verify changes in the spectrum of renal osteodystrophy. Mean serum values were: serum calcium 9.9 +/- 1.8 mg/dl, phosphate 5.8 +/- 3.2 mg/dl, alkaline phosphatase 693.9 +/- 968.9 Ul/L, iPTH 562.0 +/- 598.5 pg/ml, serum aluminum 65.7 +/- 79.3 ug/L and bone aluminum 22.8 +/- 22.4 ug/g. Hyperparathyroidism was the most common histological diagnosis as severe in 13 patients (25%), or as mild in 14 (27%). Ten patients had osteomalacia (19%), adynamic bone disease was diagnosed in 5 (9.6%) and mixed renal osteodystrophy in 10 (19.2%). Low bone turnover patients showed higher bone and serum aluminum than high bone turnover patients. We observed a relative increment in high turnover bone disease in the later period (1997-2001) without changes in low turnover bone disease. These data showed a high prevalence of hyperparathyroidism and aluminum-related low turnover bone disease, with no significant changes between the two time-periods analyzed here.

[Effect of strontium on bone metabolism in hemodialysis patients]. / Efecto del estroncio sobre el metabolismo óseo en pacientes en hemodiálisis.

The objective of this study was to assess the relationship between the bone strontium content and bone histomorphometric parameters in bone biopsies from patients with chronic renal failure undergoing hemodialysis. The study was carried out in 74 illiac crest bone biopsies from patients with renal osteodystrophy from different worldwide regions (Argentina, Portugal and Spain). They were underwent to histological and histomorphometric evaluation. The bone strontium/calcium ratio was measured by quadrupole inductively coupled plasma-mass spectrometry. The samples were classified into groups according to histological criteria: hyperparathyroidism (HP), mixed (MX), osteomalacia (OM) and adynamic bone disease (ABD). Serum PTH and alkaline phosphatase before biopsy were available in most of the patients. No correlation was found between the different histomorphometric parameters and the Sr/Ca ratio. The one way ANOVA test showed statistical differences in the Sr/Ca ratio of the different histological forms (HP: 0.58 +/- 0.39; MX: 1.16 +/- 0.74; OM: 1.10 +/- 0.46; ABD: 0.91 +/- 0.40 microgram Sr/mg Ca; p < 0.003). The post-Hoc analysis showed differences between HP and MX. The biopsies having greater or equal values than 1.4 micrograms Sr/mg Ca showed higher levels of bone formation histomorphometric parameters and serum alkaline phosphatase (395 +/- 519 vs 1,022 +/- 989 UI/L, p < 0.05). Although it has been found that the biopsies with higher bone strontium had higher levels of osteoid tissue (characteristic of osteomalacia), the hypothesis of strontium-induced osteomalacia could not be demonstrated.

[Review of the concept of vitamin D "sufficiency and insufficiency"]. / Revisión del concepto de "suficiencia e insuficiencia" de vitamina D.

There has been a poor consensus in defining normal levels of 25(OH) D. It has been traditionally recognized that 25(OH)D serum levels below 5-7 ng/ml induce osteomalacia, serum levels below 10-12 ng/ml induce secondary hyperparathyroidism and osteoporosis, and serum levels above 18-20 ng/ml are usually considered normal or adequate. Due to the results obtained in several studies, a more functional classification has recently been proposed defining serum 25(OH)D levels > 40 ng/ml or > 100 nmol/l as "desirable", serum levels between 20 and 40 ng/ml or 50 and 100 nmol/l as hypovitaminosis D, levels between 10 and 20 ng/ml or 25 and 50 mmol/l as vitamin D insufficiency and 25(OH)D levels below 10 ng/ml or 25 nmol/l as deficient. These new cut-off levels, suggest that, in the past, we had been using a wrong statistical approach for defining "normal serum 25(OH)D levels". In agreement with this new classification, in a recent study conducted in a random sample of our population, a high prevalence of low levels of 25(OH)D and secondary hyperparathyroidism was found. In our study, only in those people having "excellent" renal function, representing only 15% of the sample (serum creatinine < 1 mg/dl in men and < 0.8 in women, mean age of 68 years) hyperparathyroidism was not diagnosed despite observing 25(OH)D serum levels around 18-30 ng/ml or 45-75 nmol/l). In the remaining people (85% of the sample), who showed the expected serum creatinine increments according to their age, secondary hyperparathyroidism was avoided only if the serum 25(OH)D levels were higher than 30 ng/ml or 75 nmol/l. These remarkable findings demonstrate the importance of maintaining higher 25(OH)D levels--in addition to normal calcitriol levels--in order to avoid stimulation of the parathyroid gland. In 87 patients with a functioning renal transplantation only a 11.5% of they had levels of 25(OH)D higher than 30 ng/ml and it was correlated with PTH. These remarkable findings demonstrate the importance of maintaining higher 25(OH)D levels--in addition to normal calcitriol levels--in order to avoid stimulation of the parathyroid gland in aged people. Thus, the deficiency or even "subtle deficiency" of 25(OH)D, currently neglected in the daily management of patients with chronic renal failure, may play an important role in the maintenance of hormonal and mineral homeostasis.

[Calcitriol dose optimization in the treatment of secondary hyperparathyroidism during dialysis. Results at 6 months]. / Optimización de la dosis de calcitriol en el tratamiento del hiperparatiroidismo secundario en diálisis. Resultados a seis meses.

One recent report have recommended to start calcitriol therapy with a dose according to PTH levels, rather than starting with a fixed dose increasing it according to PTH response. As there are no clinical studies supporting this strategy we tested his hypothesis. Haemodialysis patients from 28 centres (N = 141) were included, the aim was to achieve a PTH between 100 and 285 pg/mL (goal) in 6 months. The main inclusion criteria were: serum PTH > 250 pg/mL, Ca < 10.5 mg/dL, P < 6.5 mg/dL and Ca x P < 60. Patients were divided according PTH into 4 groups and calcitriol was dosed accordingly. A (PTH 250-350; 0.5 microgram), B (PTH 351-550; 1-1.5 micrograms), C (PTH 551-750; 1.5-2 micrograms) and D (PTH < 750 pg/mL; 2-3 micrograms). PTH was measured monthly in groups A, B, C and fortnightly in D. Ca, P and Ca x P were measured fortnightly (groups A, B, C) and weekly in D. According to PTH results calcitriol was modified, reducing 50% if PTH was suppressed > 60%, and increasing 50% if PTH suppression was < 15% (fig. 1). Patients were stopped treatment and excluded from study when Ca, P and Ca x P product trespass the established inclusion criteria. The study was completed by 100 patients, 34 with strict compliance of the protocol (compliant), and 66 with one o more protocol violations, the most frequent was lack of strict adherence to the dosing regime (non compliant). Among the compliant, 82.4% reached the goal in contrast with 13.8% of the non compliant (p < 0.001) (table II). In addition, the compliant showed (all patients in all groups) a greater and significant decrease in PTH (from 616 +/- 288 to 202 +/- 82), by contrast, 21.5% of the non-compliant did not decrease--but increased--their PTH levels. The compliant showed also fewer side effects than the non-compliant (25% vs 55.6%, p < 0.006). These results demonstrate several advantages when starting calcitriol therapy with a dose proportional to the severity of HPTH.

[Progressive multifocal leukoencephalopathy in patients with AIDS: is there a change in patients treated with highly active antiretroviral therapies?]. / Leucoencefalopatía Multifocal Progresiva en pacientes con SIDA: Hay algún cambio en pacientes bajo terapias antirretrovirales de gran actividad?

AIMS: Progressive multifocal leukoencephalopathy (PML) develops in up to 4-8% of all AIDS patients. Before highly active antiretroviral therapies (HAART) the median survival was only 4-6 months. In this study we analyzed epidemiological parameters in AIDS-related LMP patients in search for differences in the incidence and prognosis between before and after HAART era. METHODS: Retrospective review of clinical histories of patients diagnosed of AIDS and PML at Hospital Meixoeiro in Vigo, Spain, between 01/01/94-31/05/97 (Before-HAART period) and 01/06/97-30/04/00 (After-HAART period). PML was diagnosed by clinical and neuroimaging criteria, with biopsy in 2 cases and positive JC virus hibridation in CSF in another case. RESULTS: We identified 12 patients (global prevalence of 3.8%, without differences between periods): 11 males, 10 intravenous drugs users (IDU), mean age of 38 years (31-43). In 6, LMP was the first opportunistic infection. When PML was diagnosed, 6 patients had a HIV viral load (VL) > 250.000 copies of RNA/ml (range, 254.003-3.170.000), and overall a mean CD4 lymphocytes counts of 89 x 10(6)/ml (40-134). Three patients received cytarabine + Interferon with zidovudine (2 patients) and zidovudine + lamivudine (1 patient) and other patient HAART + cidofovir, but no improvement was observed. The median survival was 10 months in before-HAART group and 17 months in after-HAART group, with a survival > 48 months in 2 patients in the last group. CONCLUSIONS: LMP is observed in severely immunosuppressed IDU men (VL > log 5 copies RNA/ml and CD4 < 150 x 106/ml). Complementary treatments were ineffective and only in patients with HAART a prolonged survival was observed.

Optimización de la dosis de calcitriol en el tratamiento del hiperparatiroidismo secundario en diálisis. Resultados a seis meses / Optimization of calcitriol dosis in the treatment of secondary hyperparathyroidism in dialysis. Six month results

El objetivo fundamental del estudio fue valorar la utilidad de comenzar el tratamiento con calcitriol con dosis iniciales proporcionales al grado de severidad del hiperparatiroidismo secundario. Se incluyeron pacientes de hemodiálisis de 28 centros (N = 141). El objetivo final fue alcanzar a los seis meses una PTH entre 100 y 285 pg/mL. Los criterios principales de inclusión fueron: PTH sérica > 250 pg/mL, Ca 750 pg/mL; 2-3 µg). De acuerdo a los resultados, el calcitriol se redujo al 50 por ciento si la PTH disminuía > 60 por ciento, y se incrementó un 50 por ciento si el descenso de la PTH era < 15 por ciento. Los pacientes cesaban el tratamiento y eran excluidos del estudio cuando Ca, P y Ca × P sobrepasaban lo establecido en los criterios de inclusión.El estudio fue completado por 100 pacientes, 34 con cumplimiento estricto del protocolo (cumplidores) y 66 con una o más violaciones de protocolo, siendo la más frecuente la falta de estricta adherencia al régimen de dosis (no cumplidores). Entre los cumplidores, el 82,4 por ciento alcanzaron el objetivo final, en contraste con el 13,8 por ciento de los no cumplidores (p < 0,001). Además, los cumplidores mostraron un mayor y significativo descenso de PTH (de 616 ñ 288 a 202 ñ 82), en ningún caso hubo un incremento de PTH, en contraste, el 21,5 por ciento de los incumplidores aumentaron sus niveles de PTH. Los cumplidores mostraron menos efectos adversos que los no cumplidores (25 por ciento vs 55,6 por ciento, p < 0,006). Estos resultados demuestran la ventaja de comenzar el tratamiento con calcitriol con una dosis proporcional a la severidad del hiperparatiroidismo secundario (AU)

Leucoencefalopatía Multifocal Progresiva en pacientes con SIDA: ¿hay algún cambio en pacientes bajo terapias antirretrovirales de gran actividad? / Progressive multifocal leukoencephalopathy in aids patients: any change in the highly active antiretrovi ral therapies era?

Objetivos: La leucoencefalopatía multifocal progresiva (LMP) afecta al 4-8 por ciento de pacientes con SIDA, con supervivencias de 4-6 meses antes de las terapias antirretrovirales de gran actividad (TARGA). Estudiamos las variables epidemiológicas de pacientes con SIDA y LMP para evaluar posibles diferencias en incidencia y evolución entre la época pre y postTARGA. Métodos: Revisión retrospectiva de historias de pacientes con infección VIH y LMP del Hospital Meixoeiro de Vigo entre el 01/01/9431/05/97 (periodo preTARGA) y 01/06/97-30/04/00 (periodo TARGA).El diagnóstico de LMP se realizó mediante criterios clínicos y de neuroimagen, obteniéndose confirmación biópsica en 2 casos e hibridación + para virus JC en LCR en otro caso. Resultados: Identificamos 12 pacientes con LMP (prevalencia global del 3,8 por ciento, sin diferencias entre periodos): 11 varones, 10 usuarios de drogas parenterales (UDVP), edad media de 38 años (31-43). En 6, la LMP fue la primera infección oportunista. Al diagnóstico de LMP, 6 pacientes presentaban carga viral del VIH>250.000 copias ARN/ml (rango, 254.000-3.170.000), y en todos se obtuvieron recuentos medios de CD4 de 89 x106/l (40-134). Recibieron citarabina+Interferón 3 pacientes (2 con AZT y 1 AZT+3TC) y 1 paciente TARGA+cidofovir, todos sin mejoría. La mediana de supervivencia en el grupo preTARGA fue 9 meses y en el TARGA 17 meses, observándose en 2 pacientes del último supervivencias >48 meses. Conclusiones : La LMP se observa principalmente en varones UDVP, con inmunodeficiencia avanzada (CV>log 5 copias ARN/ml y CD4<150 x106/l). Los tratamientos adyuvantes empleados fueron inefectivos y sólo en pacientes bajo TARGA se consiguieron supervivencias prolongadas (AU)

Aims: Progressive multifocal leukoencephalopathy (PML) develops in up to 4-8% of all AIDS patients. Before highly active antiretroviral therapies (HAART) the median survival was only 4-6 months. In this study we analyzed epidemiological parameters in AIDS-related LMP patients in search for differences in the incidence and prognosis between before and after HAART era. Mehods : Retrospective review of clinical histories of patients diagnosed of AIDS and PML at Hospital Meixoeiro in Vigo, Spain, between 01/01/94-31/05/97 (Before-HAART period) and 01/06/97-30/04/00 (After-HAART period). PML was diagnosed by clinical and neuroimaging criteria, with biopsy in 2 cases and positive JC virus hibridation in CSF in another case. Results: We identified 12 patients (global prevalence of 3.8%, without differences between periods): 11 males, 10 intravenous drugs users (IDU), mean age of 38 years (31-43). In 6, LMP was the first opportunistic infection. When PML was diagnosed, 6 patients had a HIV viral load (VL)>250.000 copies of RNA/ml (range, 254.000-3.170.000), and overall a mean CD4 lymphocytes counts of 89 x 10 6/ml (40-134). Three patients received cytarabine+Interferon with zidovudine (2 patients) and zidovudine+lamivudine (1 patient) and other patient HAART+cidofovir, but no improvement was observed. The median survival was 10 months in before-HAART group and 17 months in after-HAART group, with a survival >48 months in 2 patients in the last group. Conclusions: LMP is observed in severely immunosuppressed IDU men (VL>log 5 copies RNA/ml and CD4<150 x106/ml). Complementary treatments were ineffective and only in patients with HAART a prolonged survival was observed (AU)