Glucagon stimulation test to assess growth hormone status in Prader-Willi syndrome.

PURPOSE: Growth hormone deficiency (GHD) must be confirmed before starting treatment in adults with Prader-Willi syndrome (PWS). Most studies use the growth-hormone-releasing hormone plus arginine (GHRH-arginine) test. No data are available on the glucagon stimulation test (GST) in PWS. We compared the utility of fixed-dose (1 mg) GST versus GHRH-arginine test in diagnosing GHD. METHODS: Adults and late adolescents with PWS underwent both tests on separate days. In the GHRH-arginine test, GHD was defined according to body mass index. In the GST, two cutoffs were analyzed: peak GH concentration < 3 ng/mL and < 1 ng/mL. For analyses, patients were divided into two groups according to body weight (≤ 90 kg and > 90 kg). RESULTS: We analyzed 34 patients: 22 weighing ≤ 90 kg and 12 weighing > 90 kg. In patients weighing ≤ 90 kg, the two tests were concordant in 16 (72.72%) patients (k = 0.476, p = 0.009 with GST cutoff < 3 ng/mL, and k = 0.450, p = 0.035 with GST cutoff < 1 ng/mL). In patients weighing > 90 kg, the two tests were not concordant with GST cutoff < 3 ng/mL, but were concordant in 11 (91.6%) patients (k = 0.833, p = 0.003) with GST cutoff < 1 ng/mL. GH peaks on the two tests correlated (r = 0.725, p = 0.008). CONCLUSION: Fixed-dose (1 mg) GST using a peak GH cutoff of < 3 ng/mL or < 1 ng/mL promises to be useful for screening for GHD in adults and late adolescents with PWS. However, in those weighing > 90 kg, the < 1 ng/mL cutoff seems better. Larger studies are necessary to establish definitive glucagon doses and cutoffs, especially in extremely obese patients.

Impaired endothelial function is not associated with arterial stiffness in adults with type 1 diabetes.

AIM: This study investigated the relationship between endothelial dysfunction (ED) and arterial stiffness (AS) in adults with type 1 diabetes and no clinical cardiovascular (CV) disease. METHODS: A total of 68 patients with type 1 diabetes and 68 age- and gender-matched healthy (non-diabetic) subjects were evaluated. ED was assessed by reactive hyperaemia peripheral arterial tonometry (RH-PAT) and by serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin. AS was assessed by aortic pulse wave velocity (aPWV). All statistical analyses were stratified by gender. RESULTS: Adults with type 1 diabetes had RH-PAT index scores similar to those of their matching controls [men: 1.55 (1.38-1.98)% versus 1.61 (1.40-2.17)%, P=0.556; women: 2.07 (1.55-2.31)% versus 2.08 (1.79-2.49)%; P=0.215]. However, after adjusting for potential confounders, type 1 diabetes emerged as the main determinant of the RH-PAT index in women. Also, differences between genders in both the controls and type 1 diabetes patients disappeared. Men with diabetes had higher serum concentrations of E-selectin, and women had higher serum concentrations of sICAM-1, sVCAM-1 and E-selectin than their respective controls. However, after adjusting for potential confounders, only the differences in sICAM-1 (women) and E-selectin (both genders) remained significant. No association was found between aPWV and the RH-PAT index and ED markers after adjusting for CV risk factors. CONCLUSION: ED was increased in adults with type 1 diabetes compared with age-matched non-diabetic subjects. Also, gender differences in ED were lost in type 1 diabetes. However, ED was not associated with AS after adjusting for potential confounders. These findings suggest that ED occurs earlier than AS in type 1 diabetes.

Hypovitaminosis D as a risk factor of hip fracture severity.

SUMMARY: In a cross-sectional study including 324 patients older than 65 years admitted to our hospital for osteoporotic hip fracture, we found that those patients with a more severe vitamin D deficiency had more severe osteoporotic hip fractures (Garden grades III-IV and Kyle III-IV). INTRODUCTION: To identify possible differences in baseline characteristics of patients with different types of osteoporotic hip fracture. METHODS: Cross-sectional study including consecutive individuals over 65 admitted to our hospital for osteoporotic hip fracture over a year. Demographic data, fracture type, comorbidities, history of osteoporosis, functional capacity, nutritional status and vitamin D storage were evaluated. RESULTS: We included 324 patients (83 ± 7 years, 80% women). Two hundred sixteen patients (67%) had vitamin D deficiency (25OHD3 <25 ng/ml). In patients with severe femoral neck or intertrochanteric fractures (Garden III-IV and Kyle III-IV), vitamin D deficiency was more frequent (74%) and severe (25OHD3 20 ± 15 ng/ml) than in patients with less severe fractures (57%, 25OHD3 26 ± 21 ng/ml). Forty-three percent of patients had previous fractures. Only 15% of patients had been previously diagnosed with osteoporosis and 10% were receiving treatment. Patients receiving vitamin D supplements have higher 20OHD3 levels and less severe fractures. CONCLUSIONS: Although vitamin D levels are not different between patients with intracapsular or extracapsular hip fractures, a more severe vitamin D deficiency seems to be associated to more severe osteoporotic hip fractures. A prior vitamin D supplementation could avoid a higher severity of these fractures.

Insulin resistance, low-grade inflammation and type 1 diabetes mellitus.

To assess the relationships between insulin resistance and low-grade inflammation in subjects with type 1 diabetes mellitus (T1DM) who do not have clinical macrovascular complications. A total of 120 subjects diagnosed with T1DM 14 years before were evaluated for the following: (1) sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure, smoking, alcohol intake, insulin dose, HbA1c and lipid profile; (2) microvascular complications; (3) plasma concentrations of soluble fractions of tumour necrosis factor-α receptors type 1 and 2, interleukin-6, adiponectin, leptin and high-sensitivity C-reactive protein (hs-CRP); and (4) insulin resistance (estimation of the glucose disposal rate-eGDR). Those subjects with an eGDR below the median of the same sex group were classified as insulin resistant and the others as insulin sensitive. Insulin-resistant men, compared to the insulin-sensitive, had higher WHR (0.89 ± 0.08 vs. 0.83 ± 0.05; P < 0.01), higher systolic [121 (118-125) vs. 114 (108-120) mmHg; P = 0.01] and diastolic [73 (66-80) vs. 67 (70-73) mmHg; P = 0.02] blood pressures, higher HbA1c values [8.7 (8.1-9.9) vs. 7.5 (7.2-8.0) %; P < 0.01] and higher hs-CRP concentrations [1.16 (0.61-3.20) vs. 0.49 (0.31-0.82) mg/dl; P = 0.01], but no other significant differences between groups were found. Insulin-resistant women had higher WHR and HbA1c values, compared to the insulin-sensitive, but they did not have any other differences. In men, hs-CRP correlated significantly with WHR and HbA1c (r = 0.363; P = 0.016 and r = 0.317; P = 0.036, respectively), after adjusting for age, alcohol intake, smoking and microvascular complications. Insulin-resistant men with T1DM have an increase in plasma concentrations of hs-CRP. Central obesity and HbA1c are its main determinants.

Colecalciferol o calcidiol. ¿Qué metabolito utilizar en el déficit de Vitamina D? / Calciol or cholecalciferol. What metabolite should be used in vitamin D deficit?

Introducción. La hipovitaminosis D es frecuente entre la población de nuestro país. El tratamiento sustitutivo del déficit de vitamina D se puede realizar con colecalciferol o con calcidiol, pero se desconoce si estos dos metabolitos tienen una eficacia equivalente. En este estudio nos propusimos como objetivos, en primer lugar valorar la eficacia de una pauta de calcidiol para corregir en un corto plazo el déficit de vitamina D y compensar el hiperparatiroidismo secundario en pacientes con hipovitaminosis D, y en segundo lugar comparar la eficacia de dos pautas, una con calcidiol y otra con colecalciferol para mantener normales los niveles séricos de vitamina D y mantener compensado el hiperparatiroidismo secundario en pacientes con niveles ya previamente normalizados de 25-OHD3. Pacientes y métodos. Estudio prospectivo con inclusión consecutiva de todos los individuos que presentaban déficit de vitamina D, procedentes de una consulta ambulatoria de reumatología. Al inicio, y durante un mes, se realizó un tratamiento con calcidiol (16.000 UI vía oral en dosis única semanal y durante 4 semanas) para normalizar niveles de 25-OHD3. Se realizaron determinaciones en sangre (calcio, fósforo, fosfatasa alcalina, 25-OHD3 y hormona paratiroidea intacta [PTHi]) y en orina (calciuria de 24 horas) al inicio y fin del tratamiento. Los pacientes que normalizaron niveles de 25-OHD3 se incluyeron en un protocolo prospectivo aleatorizado, para mantener niveles de 25-OHD3 (con 800 UI de colecalciferol y calcio 1 g mínimo /día, o calcidiol 16.000 UI/3 semanas y el mismo aporte de calcio a diario) durante un año. A los 3,6 y 12 meses se realizaron controles analíticos. Resultados. Se incluyeron en el estudio 129 pacientes con una edad media de 72,4 [10] años. El valor medio de 25-OHD3 basal fue de 16 [5] ng/ml y el de PTHi 76 [42]. El 52% de los pacientes presentaba hiperparatiroidismo secundario. Tras el tratamiento inicial se observó normalización de los niveles de 25-OHD3 en 124 casos (96%) e hiperparatiroidismo secundario en 15 pacientes (19%). Ambos tratamientos mantuvieron unos niveles séricos de 25-OHD3 en la normalidad, pero significativamente más elevados con calcidiol (p < 0,001 a los 3, 6 y 12 meses). En un porcentaje de pacientes el tratamiento fue insuficiente para mantener los niveles de 25-OHD3, sobre todo en el grupo de colecalciferol (19% frente a 4% a los 6 meses; p= 0,04, y 18% frente a 0% a los 12 meses; p= 0,006). Conclusiones. Una pauta de 16.000 UI semanales de calcidiol, durante 4 semanas, es sumamente útil para normalizar los niveles séricos de 25-OHD3 y de PTH en pacientes con déficit de vitamina D. Calcidiol y colecalciferol son metabolitos eficaces para mantener normalizados los niveles de 25-OHD3 y de PTHi

Introduction. Hypovitaminosis D is frequent among the population of our country. Vitamin D deficiency replacement treatment may be done with cholecalciferol or with calcidiol but it is not known if these two metabolites have an equivalent efficacy. In this study, we propose the following objectives: first, evaluate the efficacy of a calcidiol regimen to correct a vitamin D deficiency in the short-term and compensate the secondary hyperparathyroidism in patients with hypovitaminosis D, and second, compare the efficacy of the two regimes, one with calcidiol and the other with cholecalciferol, to maintain serum levels of vitamin D normal and maintain the secondary hyperparathyroidism compensated in patients with levels of 25-OHD3 that have already been normalized. Patients and methods. Prospective study with consecutive enrolment of all the patients with vitamin D deficiency of outpatient rheumotology clinic. At the onset, and for one month, patients recieved calcidiol (16.000 IU orally in a single weekly dose and for 4 weeks) to normalized levels of 25-OHD3. Serum (calcium, phosphorus, alkaline phosphatase, 25-OHD3 and PTHi), and in urine (24-hour calciuria) analysis were performed at the onset and after the completion of treatment. Patients who normalized levels of 25-OHD3 were enrolled in a randomized prospective protocol to maintain levels of 25-OHD3, (with 800 IU of cholecalciferol plus calcium 1 g minimum/day or calcidiol 16.000 IU /3 weeks and the same daily suplementation of calcium), for one year. Laboratory controls were conducted at 3, 6 and 12 months. Results. 129 patients with a mean age of 72.4 [10] years were included in the study. The mean value of baseline 25-OHD3 was 16 [5] ng/ml and PTHi 76 [42]. 52% of the patients had secondary hyperparathyroidism. After the initial treatment, normalization of 25-OHD3 levels was observed in 124 cases (96%) and secondary hyperparathyroidism in 15 patients (19%). Both treatments maintained serum levels of 25-OHD3 within the nomal range, but they were significantly more elevated with calcidiol (p < 0.001 at 3, 6 and 12 months). Treatment was ineffective to maintain 25-OHD3 levels in some patients, mainly, in the cholecalciferol group (19% vs 4% at 6 months, p = 0.04, and 18% vs 0% at 12 months, p = 0.006). Conclusions. A regimen of 16.000 IU weekly of calcidiol for 4 weeks is very useful to normalize serum levels of 25-OHD3 and of PTH in patients with vitamin D deficiency. Both calcidiol and cholecalciferol are effective to maintain normalized levels of 25-OHD3 and PTHi

Administración de calcidiol y valores séricos de 25-OH-D3. ¿Qué pauta clínica utilizar? / Calcidiol treatment and serum 25-OHD3 levels. What treatment regimen should be used?

Objetivo: Valorar la eficacia de 3 dosis distintas de calcidiol para corregir y mantener unos valores de 25-OH-D3 normales, en pacientes con hipovitaminosis D, controlados en consulta externa de reumatología. Sujetos y métodos: Ensayo terapéutico aleatorizado no controlado, con inclusión sistemática de todos los pacientes con hipovitaminosis D, de una consulta externa de reumatología. El estudio incluyó a 70 pacientes (11 varones y 59 mujeres) con una edad media ñ desviación estándar (DE) de 70 ñ 11 años. Todos los pacientes incluidos recibieron tratamiento sustitutivo con calcio (1-1,5 g/día) y calcidiol una dosis inicial de 16.000 U a la semana durante 4 semanas y una dosis de mantenimiento variable: 16.000 U cada mes, cada 3 semanas o cada 2 semanas. Durante el seguimiento (28 ñ 14 meses) se realizaron 306 determinaciones de 25-OH-D3 de control, con una media ñ DE de 4,3 ñ 1,2 (3-9) por paciente. Resultados: Las 3 pautas de tratamiento mantuvieron unos valores medios de 25-OH-D3 normales y sin diferencias significativas entre ellas.La mayoría de determinaciones de 25-OH-D3 fueron normales en los 3 tratamientos y durante el seguimiento (un 97 por ciento con calcidiol mensual, un 100 por ciento con calcidiol cada 3 semanas y un 97 por ciento con calcidiol cada 2 semanas; p = NS). Durante el seguimiento no se observó ningún efecto secundario clínicamente relevante asociado al tratamiento. Conclusiones: El calcidiol es eficaz para compensar la hipovitaminosis D. Una dosis inicial de 16.000 U cada semana durante 4 semanas y una dosis posterior de mantenimiento cada 3 o 4 semanas son probablemente suficientes para mantener unos valores séricos de 25-OH-D3 adecuados (AU)

Impacto de un sistema de evaluación sobre los programas de posgrado / The impact of an evaluation system of postgraduate programs

Introducción. Se expone nuestra experiencia en la utilización del sistema de evaluación de especialistas en formación y de servicios docentes regulado por la Orden Ministerial de 22 junio de 1995. Métodos. Los servicios docentes y los especialistas en formación han sido valorados en 1995, 1996 y 1997. De los servicios docentes se han evaluado las rotaciones individuales y el servicio en conjunto. Los especialistas en formación se han agrupado por período de formación y se han evaluado respecto a conocimientos, habilidades y actitudes. Las evaluaciones han sido realizadas por los tutores y los facultativos responsables. Se han buscado diferencias interanuales e intergrupo utilizando los tests ANOVA y no paramétrico de Wilcoxon. Resultados. En los resultados obtenidos por los especialistas en formación se han encontrado diferencias estadísticamente significativas: a) interanuales e intergrupo en la evaluación de conocimientos y habilidades; b) al comparar las valoraciones realizadas por los tutores con las que hacen los facultativos responsables, y c) al comparar los resultados de conocimientos y habilidades con los de actitudes. Con respecto a los servicios docentes hay diferencias: a) interanuales en la valoración del servicio, y b) al comparar los resultados de las rotaciones con los del servicio. Conclusiones. El sistema descrito ha sido una herramienta útil para evaluar a los especialistas en formación y los servicios docentes. Creemos que para mejorarlo sería necesario establecer cuestionarios de evaluación y objetivos docentes distintos para cada período de formación. La labor de los tutores y de las comisiones de docencia es indispensable para que las evaluaciones adquieran un aspecto formativo y de mejora de los programas de posgrado (AU)

Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo.

We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury.