Consenso chileno para la atención integral de niños y adultos con fibrosis quística

Resumen La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

Consenso chileno para la atención integral de niños y adultos con fibrosis quística / Chilean consensus for the integral care of children and adults with cystic fibrosis

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

Frecuencia de anticuerpos anti-transglutaminasa y antiendomisio en pacientes con diabetes tipo 1 / Association of type 1 diabetes mellitus with celiac disease

Background: Type 1 diabetes mellitus and celiac disease share common genetic and immunological aspects and celiac disease is more common among type 1 diabetic patients. Aim: To determine the frequency of anti endomysial and anti transglutaminase antibodies among patients with type 1 diabetes. Material and Methods: Anti endomysialantibodies determined by indirect immunofluorescence an anti transglutaminase antibodies determined by ELISA were measured in 410 serum samples of patients with type 1 diabetes. Results: Seventy one samples (17 percent) had positive anti transglutaminase antibodies. Among these, 17 had also positive anti endomysial antibodies. In 11 of these 17 patients, the presence of celiac disease was confirmed. Conclusions: Among patients with type 1 diabetes mellitus, the frequency of celiac disease is three times higher than in the general population.

Marcadores de inflamación y autoinmunidad en pacientes con diabetes tipo 1 / And inflammation markers in patients with diabetes autoimmunity type 1

To determine the serological levels of inflammatory markers and autoimmunity in patients with T1D compared with controls, and determined its relation to the duration of diabetes. Methods: We selected 139 patients with T1D without chronic complications of diabetes, and 110 control subjects without family history of diabetes. Serological ultrasensitive C-reactive protein levels (usCRP), interleukin- 6 and adhesion protein VCAM through ELISA assay were determined. Autoimmune profile was also analyzed through GAD65, IA-2 and ZnT8 autoantibodies. Results: Increased levels of usCRP 1.74 (0.10 to 13.6) vs 1.08 (0.40 to 3.70) ng/ml (p < 0.03), VCAM 236.0 (122.2 to 693.5) vs 185.4 (101.3 to 421.3) ng/ml, p < 0.02 and IL-6 1.73 (0.40 to 9.10) vs 1.28 (0.30 to 4.60) ng/ml, p < 0.05 was found in the group of T1D patients compared with the control group. When analyzing inflammatory markers according to age groups (0-10 years and > 10 years), the values of usCRP were higher in the second group. There was no significant association between patients with DM1 and autoimmune positive profile with a higher frequency of markers of inflammation. Conclusions: These results suggest the presence of pro-inflammatory state is considerably more frequent in patients with T1D. The increased level of usCRP and IL -6 and according to age of the patients could indicate a possible role of adiposity and weight gain during the adolescence in the higher frequency of inflammatory markers in T1D patients...

Síndrome metabólico en niñas púberes con hiperplasia suprarrenal congénita clásica / Metabolic syndrome among puberal girls with classic congenital adrenal hyperplasia

Background: Adult women with adrenal congenital hyperplasia (AH) have a higher risk for insulin resistance, dyslipidemia, hypertension, high body mass index (BMI) and increased body fat. All these factors are associated with cardiovascular risk and metabolic syndrome (MS). Aim: To evaluate the presence of MS in pubertal classic AH girls (CAH) and a control group (C). Material and Methods: We studied 15 pubertal AH patients (12.0 +/- 1.9 years) and 26 controls (11.7+/- 0.3 years) matched by age and tanner stage. Weight, height, BMI, waist/hip ratio, blood pressure and serum lipids were measured. An oral glucose tolerance test (OGTT) and insulin curve was performed in CAH girls whereas in controls basal insulin and glucose were determined. The homeostasis model assessment for insulin resistance (HOMAIR) was calculated. Cook, Ferranti and international diabetes federation (IDF) criteria were used to determine the presence of MS. Results: CAH and C girls had similar BMI (22.0 +/- 5.1 and 20.1 +/- 3.6 kg/m2 respectively; p = 0,11). CAH girls had higher basal blood glucose (80.8 +/- 7.7 and 60.6 +/- 10.6 mg/dl respectively, p < 0.01) and controls had higher triglyceride levels (147.0 +/- 69.3 and 79.7 +/-16.3 mg/dl respectively, p < 0.01) and lower HDL cholesterol levels (45.8 +/- 12.8 and 56.9 +/- 17.5 mg/dl respectively, p = 0.02). According to cook criteria 4 percent of CAH girls and 23 percent of controls has MS. These figures were 14 and 32 percent respectively according to Ferranti criteria and 0 and 5 percent respectively according to IDF criteria. Conclusions: CAH puberal patients do not have a higher prevalence of metabolic syndrome, compared with controls with similar Tanner stage and BMI.

[+49 A/G genetic polymorphism of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) in type 7 diabetes: association with autoantibodies and cytokines]. / Polimorfismo +49 A/G del gen del antígeno 4 del linfocito T citotóxico (CTLA-4) en la diabetes tipo 1: Asociación con el perfil de anticuerpos y citoquinas.

BACKGROUND: Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) has been one ofthe non HLA genes more commonly studied in type 1 diabetes mellitus (TID). CTLA-4 is a co-stimulation protein that has a key role in the negative regulation ofT cells and is related with a functional cytokine imbalance, generating a T helper (Th) 1 over Th2 dominance. AIM: To analyze the association of +49 A/G polymorphism of CTLA-4 and its relationship with autoantibodies and cytokine expression in recently diagnosed TID patients. PATIENTS AND METHODS: CTLA-4 genetic variants and auto-antibody levéis were studied in 260 chiídren with TID and 255 healthy chiídren matched by age and gender +49 A/G polymorphism of CTLA-4 was studied by polymerase chain reaction and restriction fragmentpolymorphism (PCR-RFLP). Autoantibody levéis were measured by conventional ELISA. A panel of60 cytokines was studied simultaneously by serum array analysis in 15 TID and 15 healthy controls stratified according CTLA-4 genotype. RESULTS: The +49 A/G genetic frequency was similar in TID cases and healthy chiídren. A positive anti-GAD65 and anti-IA-2 level was observed in 673% of TID group. This percentage was increased among GG carriers (79.4% to GAD65 and 70.6% to IA-2). Finally, TID patients carrying this genotype showed a high expression of interleukin 2, 10, tumor necrosis factor alpha and interferon gamma. CONCLUSIONS: The +49 A/G polymorphism of CTLA-4 was similar in diabetic and control chiídren. Among patients with TID and carriers of GG genotype, a higher frequency of anti-GAD65 and a preferential Thl cytokine expression profile was observed.

Polimorfismo +49 A/G del gen del antígeno 4 del linfocito T citotóxico (CTLA-4) en la diabetes tipo 1: Asociación con el perfil de anticuerpos y citoquinas / +49 A/G genetic polymorphism of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) in type 7 diabetes: Association with autoantibodies and cytokines

Background: Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) has been one ofthe non HLA genes more commonly studied in type 1 diabetes mellitus (TID). CTLA-4 is a co-stimulation protein that has a key role in the negative regulation ofT cells and is related with a functional cytokine imbalance, generating a T helper (Th) 1 over Th2 dominance. Aim: To analyze the association of +49 A/G polymorphism of CTLA-4 and its relationship with autoantibodies and cytokine expression in recently diagnosed TID patients. Patients and Methods: CTLA-4 genetic variants and auto-antibody levéis were studied in 260 chiídren with TID and 255 healthy chiídren matched by age and gender +49 A/G polymorphism of CTLA-4 was studied by polymerase chain reaction and restriction fragmentpolymorphism (PCR-RFLP). Autoantibody levéis were measured by conventional ELISA. A panel of60 cytokines was studied simultaneously by serum array analysis in 15 TID and 15 healthy controls stratified according CTLA-4 genotype. Results: The +49 A/G genetic frequency was similar in TID cases and healthy chiídren. A positive anti-GAD65 and anti-IA-2 level was observed in 673 percent of TID group. This percentage was increased among GG carriers (79.4 percent to GAD65 and 70.6 percent to IA-2). Finally, TID patients carrying this genotype showed a high expression of interleukin 2, 10, tumor necrosis factor alpha and interferon gamma. Conclusions: The +49 A/G polymorphism of CTLA-4 was similar in diabetic and control chiídren. Among patients with TID and carriers of GG genotype, a higher frequency of anti-GAD65 and a preferential Thl cytokine expression profile was observed.

Interactions between programmed death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) gene polymorphisms in type 1 diabetes.

AIM: To explore the contribution of the PD-1 gene polymorphisms involved in T1D as well as the relationship between the PD-1/CTLA-4 genes and soluble CTLA-4 concentrations. PATIENTS AND METHODS: 261 incident cases of T1D and 280 healthy children less 15 years old were included in this study. Haplotypes for polymorphisms of the PD-1 and CTLA-4 genes were determined by PCR and RFLP methods. Screening for soluble CTLA-4 was done using an ELISA assay. Statistical analysis was performed using the online SHESIS package. RESULTS: Our results show that sCTLA-4 levels were higher in T1D than in controls (2.99+/-1.7 ng/ml versus 1.43+/-0.31 ng/ml, p<0.001). The allele dosage of CTLA-4 on PD-1 haplotypes, showing a significant modified effect of G carriers over AA genotype on the sCTLA-4 concentrations (5.48+/-2.09 ng/ml versus 3.27+/-1.30 ng/ml, p<0.03 in T-C haplotype) and (1.92+/-0.79 ng/ml versus 3.41+/-1.10 ng/ml, p<0.02 in C-T haplotype). CONCLUSION: Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 is elevated in T1D. Our data suggest a possible gene dosage effect of "G"CTLA-4 carriers on sCTLA-4 over the possible protective or susceptible effect conferred by PD-1 haplotypes.

Insulinoma, presentación y evolución de dos casos clínicos / Insulinoma, evolution and presentation of 2 clinical cases

Insulinoma is a very uncommon tumor in children, with an incidence in adults of 2 per million inhabitants. Clinical manifestations include neuroglycopenic or autonomic manifestations due to hypoglycemia. We describe 2 pediatric patients with insulinoma, characterized by repeated episodes of hypoglycemia associated to high insulin serum levels and presence of a small mass in the pancreas by imaging studies. The diagnosis was very prompt in one case and delayed in the other, emphasizing the need for an appropriate diagnosis of hypoglycemia during childhood.

El insulinoma es un tumor muy infrecuente en la edad pediátrica y la incidencia reportada en adultos es de 2 casos por millón de habitantes. La presentación de la enfermedad consiste en la presencia de síntomas neuroglicopénicos y autonómicos desencadenados por los episodios de hipoglicemia. Se describen dos pacientes con insulinoma esporádico. El cuadro clínico consistió en episodios repetidos de hipoglicemia asociados a niveles aumentados de insulina sérica y a imágenes sugerentes de un tumor pancreático. El diagnóstico fue muy oportuno en uno de los casos y muy tardío en el otro, lo que resalta la necesidad de estar muy alerta ante casos de hipoglicemia durante la niñez.

Adelanto de la pubertad en Chile y el mundo / Timing of puberty: secular trend toward earlier development in Chile and variations around the world

La menarquia se ha adelantado progresivamente desde mediados del siglo XIX, hecho conocido como tendencia secular de la menarquia, fenómeno que parece ser una característica evolutiva del ser humano en relación al mejoramiento de las condiciones de vida. Sin embargo, durante los últimos treinta años la edad de la menarquia se ha mantenido estable. A diferencia de la menarquia, la telarquia está ocurriendo a una edad más precoz que hace algunas décadas y es frecuente encontrar casos de telarquia aislada en niñas menores de 8 años. En el varón, en cambio, no hay evidencias de que su desarrollo esté ocurriendo más tempranamente. En el presente artículo, se discute la etiología del adelanto puberal y los factores que se deben tomar en cuenta en las pacientes para decidir un eventual estudio y tratamiento.

Diabetes Mellitus tipo 1 (DM1) en niños menores de 5 años: Características al debut vs otros grupos etarios en Chile / Type I diabetes mellitus in Chilean children under 5 years-old: Onset characteristics in contrast with other age groups

Introducción: En los últimos años, se ha visto un aumento en la incidencia de DM1 en niños. Objetivo: Determinar frecuencia y características clínicas y de laboratorio al debut de DM1 en niños chilenos menores de 5 años, comparado con los de mayor edad. Pacientes y Métodos: Se estudiaron los datos clínicos y de laboratorio de pacientes que debutaron entre 1998-2003 en cuatro centros de Santiago. Se clasificaron en 3 grupos etarios (G): 0-4 (GI), 5-9 (GII) y 10-14 años (GIII) y se compararon según los parámetros descritos. Resultados: Un 19,7 por ciento de los pacientes eran menores de 5 años; GI (n = 27), seguido de aquéllos pertenecientes a GII (43,8 por ciento; n = 60) y GIII (36,5 por ciento; n = 50). El periodo de síntomas previo al diagnóstico fue más corto en GI; 18,4 ± 23,7 vs 26,4 ± 27,4 y 40,1 ± 60 días (p < 0,0001) y su nivel de HbA1c fue más baja; 10,1 ± 1,7 vs 11,8 ± 3,4 por ciento en GII (p < 0,0001) y 12,4 ± 2,6 por ciento en GIII (p = 0,028), respectivamente. No hubo diferencias en la glicemia inicial entre los grupos. La acidosis metabólica fue mayor en GI; pH 7,14 ± 0,1 vs 7,19 ± 0,2 (GII) y 7,26 ± 0,1 (GIII) (p < 0,0001) y presentaron más infecciones concomitantes (33 por ciento, 20 y 28 por ciento respectivamente; p > 0,05). Conclusiones: Un porcentaje importante de las DM1 se inicia en niños < 5 años. Este grupo presenta un cuadro más grave, con mayor acidosis, menores niveles de HbA1c y periodo previo de síntomas, por lo que debe existir alerta para el diagnóstico en este grupo etario.

Background: During the last years, an increase in the incidence of DM1 in infants has been observed. Objective: to study the number of children younger than 5 years-old diagnosed with DM1 and compare clinical and laboratory features with older children at DM1 onset. Method: Study of the clinical and laboratory characteristics in subjects diagnosed with DM1 from 1998 to 2003 in Santiago. Patients were classified according to age in 3 groups: 0-4 (GI), 5-9 (GII) and 10-14 years-old (GIII). Results: 19,7 percent cases were younger than 5 years-old (GI n = 27), GII (43,8 percent n = 60) and GIII (36,5 percent n = 50). A shorter duration of symptoms was observed in GI (18,4 ± 23,7 vs 26,4 ± 27,4) (p < 0,0001) and HbA1c levels were lower in GII (10,1 ± 1,7 vs 11,8 ± 3,4 percent) (p < 0,0001) and in GIII (12,4 ± 2,6 percent) (p = 0,028). Glucose levels were similar among groups (p>0,05) and metabolic acidosis was more severe in GI (pH 7,14 ± 0,1 vs 7,19 ± 0,2 in GII and 7,26 ± 0,1 in GIII) (p < 0,0001). A concomitant infectious disease was observed in GI (33 percent), GII (20 percent) and GIII (28 percent) (p > 0,05). Conclusions: An important percentage of DM1 in children presents in subjects younger than 5 years-old. This group showed acute and severe clinical presentation with longer duration of symptoms, severe acidosis and lower HbA1c levels. It is necessary to evaluate carefully in order to suspect the diagnosis in this group.

Nuevos esquemas de tratamiento con insulina en niños y dolescentes con Diabetes Mellitus tipo 1 (DM1) en un Hospital Público / New schemes of insulin treatment in children and adolescents with type 1 diabetes mellitus attending a Public Hospital

En la última década se ha demostrado la importancia del control glicémico en la prevención de las complicaciones microvasculares de la DM1. Para lograr este objetivo se ha propiciado el uso de esquemas terapéuticos de insulina intensificados. Objetivo: Comunicar los nuevos esquemas terapéuticos que se utilizan en niños y adolescentes con DM1 y sus resultados en el control metabólico. Método: Se evaluaron los esquemas insulínicos utilizados por todos los pacientes < 19 años en control durante 2003, clasificándolos en tratamiento intensificado (doble o triple dosis de NPH o Glargina) o convencional (< 2 dosis/día). Se consignaron las dosis utilizadas, la HbA1c promedio, el resultado del programa educativo (conocimiento de cantidad de hidratos de carbono, intercambio de alimentos, cambio de dosis según ingesta de hidratos de carbono (HdC) y proporción Insulina/ HdC) y se compararon los resultados obtenidos con las distintas modalidades de tratamiento. Resultados: Se estudiaron 69 pacientes con DM1 (36 mujeres), de 12,0 ± 3,7 años (2-19 años), 59,7% púberes. Todos utilizaban una insulina basal (69,2% de la dosis diaria) y otra prandial; 87% de los pacientes requirieron tres o más dosis diarias de insulina y 13% utilizaba esquema convencional de dos dosis de NPH. Los pacientes en tratamiento intensificado recibían tres o cuatro dosis diarias de insulina prandial, con los siguientes esquemas de insulina basal: dos dosis diarias de NPH (28%), glargina (10%) y tres dosis diarias de NPH (49%). 88,4% de los pacientes modificaba la dosis de insulina rápida según la glicemia y 46,4% consideraba la ingesta de HC; 27% conocía la relación HdC/insulina y 79,7% se colocaba refuerzos adicionales de insulina al comer fuera de sus horarios. La HbA1C del grupo fue de 8,6 ± 1,4%; 30,4% de los pacientes logró el objetivo de HbA1c establecido en el programa, sin diferencias respecto al esquema de insulinoterapia basal utilizado. Por análisis de ...

Introduction: During the last decade the importance of glycaemic control in the prevention of microvascular complications of type 1 diabetes mellitus (DM1) has been demostrated. To achieve this goal, different modalities of intensive therapy have been recommended. Objective: To communicate a novel therapeutic modality employed in paedriatric patients and the metabolic control achieved. Methods: All DM patients < 19 years were included. Insulin treatment was consigned and classified as intensive (at least 3 daily doses, 2 or 3 NPH daily doses, or glargin) or conventional (2 or less doses). Number of doses, mean HbA1c during 2003, results of educative programmes were evaluated and compared. Results: 69 patients (36 females) were studied, 59,7% were pubertal, with a mean age of 12,0 ± 3,7 years. All patients used a basal insulin (69,2% daily dose) and a prandial insulin. Intensive therapy was used by 87% of children. Patients with multiple daily doses received 3 or 4 inyections of a short or rapid acting insulin. Basal insulin was glargine in 10%, twice daily NPH in 28% and thrice daily in 49%. Patients modified dose according to glucose level occured in 88,4%, and 46,4% considered carbohydrate intake. 27% knew the carbohydrate/insulin ratio and 79,7% used additional insulin when eating extra carbohydrates. The BbA1c was 8,6 ± 1,4% without differences in terms of insulin modality used. 30,4% achieved the proposed goals of HbA1c. The total and basal insulin usage correlated with the HbA1c. Conclusions: Multiple modalities of insulin therapy are available, no difference in metabolic control between the modalities was detected. We have achieved very good control in 30% of the patients, only insulin daily dose and basal dose correlated significatively with HbA1c.

Cronología del desarrollo puberal en niñas escolares de Santiago: relación con nivel socio-económico e índice de masa corporal / Age of pubertal events in Chilean school age girls and its relationship with socioeconomic status and body mass index

Background: Recent studies in the United States have demonstrated that a significant proportion of girls show thelarche before the age of eight years. Nutritional status, geographic influences and racial factors are known to affect the timing of puberty. Aim: To evaluate the age of onset of puberty, development of secondary sexual characteristics and menarche in Chilean girls, and its relation to obesity and socioeconomic status. Material and methods: Healthy girls attending elementary school, from first to ninth grade in Santiago, Chile, were studied. A pediatric endocrinologist evaluated pubertal development using Tanner classification. Breast development was assessed by inspection and breast palpation. Average age of onset of pubertal events was determined by probit analysis. Results: A total of 758 girls, aged 5.8 to 16.1 years, were recruited. Obesity, defined as a BMI greater than 90th percentile, was found in 24.4 percent. The age of menarche was 12.7 years, the onset of Tanner stage 2 breast development and pubic hair was at 8.9 and 10.4 years, respectively. Sixteen percent of girls aged 7 to 7,9 years, had thelarche. Upper class girls showed a later onset of breast Tanner stage 4 stage than low-middle class girls. Obesity was not found in logistic regression analysis to be a significant predictive factor in the onset of puberty. Conclusions: The age of menarche has not changed in the last thirty years, but an earlier onset of thelarche has occurred. The high frequency of thelarche between 7 and 8 years suggests that the normal age of breast development should be revised.

Estudio clínico molecular de pacientes chilenas con síndrome de McCune-Albright / Clinical and molecular study of Chilean patients with McCune-Albright Syndrome

Background: McCune-Albright Syndrome (MAS) is characterized by precocious puberty, "cafe au lait" skin lesions and polyostotic fibrous dysplasia. It is caused by 4 post-zygotic mutations of Gas protein with a mosaic distribution. Aim: To describe the clinical presentation and to investigate the presence of the Arg by his substitution (R201H) in 14 girls with MAS. Patients and methods: We performed a clinical analysis of the patients and specific allele PCR in DNA obtained from leukocytes. Results: Twelve of 14 patients presented with precocious puberty, one with cyclical vaginal bleeding and one with pathological bone fractures. Eight girls had polyostotic fibrous dysplasia, one had hyperthyroidism, four had pathological fractures, ten had ovarian cysts, six had breast hyperpigmentation and ten had "cafe au lait" skin lesions. We detected the R2O1H mutation in 10 of 14 patients. We found no difference in the severity of symptoms or in the age of presentation between the patients with and without the mutation. Conclusions: The R201H mutation can be detected in white blood cells, in approximately 70 per cent of cases. Patients exhibit wide clinical variability with the same molecular defect. This suggests that tissues have different proportions of mutant cells

Utilidad de la determinación del factor de crecimiento insulino-simil tipo I (IGF-I) y de su proteína ligante tipo 3 (IGFBP-3) en el diagnóstico de la deficiencia de hormona de crecimiento en niños / Usefulness of the measurement of insulin-like growth factor 1 (IGF-I) and IGF-1 binding protein-3 (IGFBP-3) for the diagnosis of growth hormone (GH) deficiency in children

Background: The diagnosis of GH deficiency (GHD) is based upon the results of GH stimulation tests, which have several drawbacks. Aim: To evaluate the usefulness of IGF-1 and IGFBP-3 for the diagnosis of GHD in prepuberal children. Material and methods: We measured IGF-I and IGFBP-3 in three group of subjects: I. GHD (n:24), height <-2SD for age (Z score, average ñ SD: -4.2 ñ 1.2), growth velocity 7 ng/ml (15.3 ñ 6.9 ng/ml), y III. Normal school children (n:35) with normal heights (-0.17 ñ 0.12 SD) were studied as controls. Results: IGF-1 and IGFBP-3 were significantly lower in GHD than in NGHD and controls (p <0.001), and in NGHD than in C (p <0.001). We defined the normal range of both proteins as ñ 2 SD of the mean of the control group. Using this criteria, IGF-I was low in 21/24 GHD, and in 12/32 NGHD. IGFBP-3 was low in 22/24 GHD, and in 6/32 NGHD. Only 1 GHD patient had both exams in the normal range, suggesting that he is probably NGHD. 4/32 of the NGHD had both exams below normal range, suggesting that they are probably GHD. Conclusions: IGF-1 and IGFBP-3 are important tools for the diagnosis of GHD

Gonadoblastoma bilateral en una niña con isocromosoma 46, X, i (Y) (q10) / Bilateral gonadoblastoma in a girl with isochromosome 46, X, i (Y) (q10)

Niño de 6 años derivado por tallo bajo con micrognatia, paladar ojival, cuello alado, aréolas pequeñas y bajas, cúbito valgo, acortamiento del cuarto metacorpiano y escoliosis, que sugerían síndrome de Turner. En su cariotipo se identificó un isocromosoma del brazo largo del cromosoma Y: 46, X, i (Y) (qIO). En la ultrasonografía el útero tenía aspecto prepuberal y los ovarios no se identificaron. Se exploró mediante cirugía extirpando ambas gónadas, debido al riesgo de desarrollar un tumor gonadal dado la presencia de un cromosoma Y. En el examen histopatológico se encontraron esbozos de trompas y características de gonadoblastoma

Hepatitis crónica activa en un caso de hipertiroidismo severo / Active chronic hepatitis in a severe hyperthiroidism case

Se describe una adolescente que sufría de hipertiroidismo severo de larga evolución, con pobre respuesta a medicamentos antitiroideos y dos episodios de ictericia previos, que ingresó con un hipertiroidismo clínicamente activo a pesar de estar recibiendo propiltiouracilo, ictericia intensa y hepatomegalia. El estudio y manejo de su hepatitis fue complejo, dado que las posibilidades de disfunción hepática en el contexto de un hipertiroidismo, podrían obedecer a toxicidad por drogas, insuficiencia cardíaca, hipertiroidismo por sí mismo o hepatitis autoinmune. Se manejó con suspensión del propiltiouracilo, régimen hipercalórico, propanolol y dos dosis de I131, con lo cual se logró controlar el hipertiroidismo. El estudio de laboratorio e histopatológico fue compatible con hepatitis crónica activa que se manejó con corticoides orales, coincidiendo con lo cual la paciente está asintomática, si bien la biopsia hepática muestra aún signos de actividad

Proteína C reactiva en síndrome diarreico agudo / C-reactive protein in acute diarrhea syndrome

La proteína C reactiva se ha usado en múltiples enfermedades infecciosas en la orientación de la etiología viral o bacteriana; su utilidad en relación al síndrome diarreico agudo (SDA) se desconoce. Con la hipótesis que las infecciones bacterianas enteroinvasoras muestran un valor mayor de PCR que las virales, se estudiaron 47 niños con SDA. Se realizaron: PCR, 2 coprocultivos, tinción violeta bicarbonato de Hucker y aislamiento de rotavoris por inmunoelectroforesis. Se detectaron 11 casos con bacteria enteroinvasoras en deposiciones, 9 con rotavirus , 1 mixto y 26 pacientes con estudio etiológico negativo. Para las infecciones virales el promedio, mediana y rango de PCR fueron (mg/lt): 13,55; 8; (0-75) y para las bacterias invasoras fueron: 116,7; 116; (1-318) respectivamente (p<0,01). Ocho de 11 niños con infección bacteriana mostraron PCR > 30 mg/lt versus 1 de 9 con infección viral (p=0,0091); 7 de los primeros tuvieron valores > 100 mg/lt. Los resultados obtenidos confirman nuestra hipótesis