Hipercolesterolemia familiar. Enfoque desde la Pediatría / Familial hypercholesterolemia. A pediatric focus

La Hipercolesterolemia Familiar (HF) es una enfermedad hereditaria frecuente que se caracteriza por niveles elevados de colesterol ligado a las lipoproteínas de baja densidad (C-LDL). El exceso de LDL se acumula en las arterias produciendo aterosclerosis prematura. El diagnóstico y tratamiento desde la infancia mejoran el pronóstico de la enfermedad. Existe subdiagnóstico de la HF lo que provoca muertes prematuras por enfermedad cardiovascular (ECV). Para mejorar el subdiagnóstico la Sociedad Argentina de Pediatría propuso en el año 2015 realizar tamizaje universal al ingreso escolar. Es relevante entonces que el pediatra pueda diagnosticar la hipercolesterolemia y diferenciar las hipercolesterolemias monogénicas o familiares, de las secundarias (AU)

Familial hypercholesterolemia (FH) is a common hereditary disease that is characterized by high cholesterol levels, linked to low-density lipoproteins (LDL). Excess LDL accumulates in the arteries leading to premature atherosclerosis. Early diagnosis and treatment since childhood improve the prognosis of the disease. FH is underdiagnosed resulting in premature death due to cardiovascular disease (CVD). To improve diagnosis, in 2015 the Argentine Society of Pediatrics proposed a universal screening program at school age. It is relevant, therefore, for the pediatrician to be able to diagnose hypercholesterolemia and differentiate monogenic or familial from secondary hypercholesterolemia (AU)

Prevalencia de factores de riesgo de enfermedad cardiovascular en niños y adolescentes con infección por HIV / Prevalence of risk factors for cardiovascular disease in HIV-infected children and adolescents

Introducción: La exposición prolongada a las drogas en el tratamiento antirretroviral de alta eficacia (HAART) cambió el pronóstico de la enfermedad pero puede generar alteraciones metabólicas y lipodistrofia que aumentan el riesgo de enfermedad cardiovascular precoz (ECVP). En la población pediátrica infectada con HIV los estudios son escasos y las medidas para disminuir el riesgo de ECVP no han sido definidas. Objetivo: investigar la prevalencia de factores de riesgo de ECVP en niños y adolescentes con infección crónica por HIV en un hospital pediátrico de alta complejidad. Material y Métodos: estudio descriptivo, prospectivo, controlado, de corte transversal. Se incluyeron niños con infección vertical por HIV, edad entre 2 y 18 años estratificados según esquema de tratamiento antirretroviral recibido (con y sin Inhibidores de la Proteasa-IP-) y controles seronegativos. Se realizó antropometría, impedanciometría bioeléctrica (BIA)y ecodoppler carotídeo. Se dosó glucemia basal, insulina basal, perfil lipídico, TGO, TGP, recuento de leucocitos y plaquetas, linfocitos TCD4+ y TCD8+, carga viral, proteína C Reactiva cuantitativa de alta sensibilidad. Se consideraron pacientes con riesgo de ECVP a los que presentaron: obesidad, hipertensión arterial, intolerancia a la glucosa/ diabetes, resistencia a la insulina, dislipemia, aumento de proteína C reactiva (PCR) o aumento del grosor arterial. Resultados: Ambos grupos HIV+ presentaron un escore Z para peso, talla y BMI significativamente menor que el grupo control., mientras que la frecuencia de aparición del índice Cintura/Talla con valores patológicos fue significativamente mayor en el grupo HIV+. Utilizando el método clínico de Carr el 18% de los pacientes HIV+ presentaba lipodistrofia, la mayoría de los cuales tenían hipertrigliceridemia. El grupo HIV+ presento un% de masa grasa (MG) mayor y un% de masa libre de grasa (MLG) y masa celular menor que el grupo control medido por BIA. Se constató alta prevalencia de dislipidemia en el grupo HIV+ con niveles medios más altos de Colesterol total, c-LDL, y TG que el grupo control, que fue significativamente mayor en los pacientes expuestos a IP con valores más elevados de colesterol total y c-LDL y mayor frecuencia de alteración del índice CT/HDL y significativamente mayor en el grupo expuesto a IP. No se encontraron diferencias de los niveles medios de glucemia en ayunas, insulina basal ni resistencia a la insulina evaluada por HOMA. En el subgrupo HIV+ estudiado se observó un aumento del espesor de la íntima media carotidea. Conclusión: En un grupo de niños y adolescentes infectados verticalmente por HIV bajo TARV de alta eficacia el peso, talla,% de MLG y MC fue significativamente menor y el% de MG mayor que el grupo control. La alta prevalencia de dislipidemia encontrada en el grupo HIV+, particularmente en aquellos expuestos a IP y el indice Cintura/Talla constituyen factores que aumentarían el riesgo de desarrollar enfermedad cardiovascular precoz (AU)

Introduction: Long-term drug exposure using highly active antirretroviral therapy (HAART) has changed disease prognosis in HIV-infected patients, but may cause metabolic alterations and lipodystrophy increasing the risk of early cardiovascular disease (ECVD). Studies in the population of HIV-infected children are scarce and measures to reduce the risk of ECVD have not been defined. Aim: To investigate the prevalence of risk factors for ECVD in children and adolescents with a chronic HIV-infection in a tertiary pediatric. Material and Methods: A descriptive, prospective, controlled cross-sectional study was conducted. Children with a mother-to-child HIV infection between 2 and 18 years of age, stratified according to HAART regimen received (with or without protease inhibitors (PI)) and seronegative controls were included. Anthropometry, bioelectrical impedance analysis (BIA), and carotid ultrasonography were performed. Baseline glycemia and insulin, lipid profile, ALT, AST, leukocyte and platelet counts, TCD4+ and TCD8+ lymphocytes, viral load, and high-sensitivity quantitative C-reactive protein (CRP) were measured. Patients were considered at high risk for ECVD when they had: obesity, arterial hypertension, glucose intolerance/diabetes, insulin resistance, dyslipidemia, increased CRP, or increased intima-media thickness. Results: Both HIV+ groups presented with significantly lower Z-scores for weight, height, and BMI than the control group, while the prevalence of pathological measures of waist-to-height index was significantly higher in the HIV+ group. Using the clinical method of Carr, 18% of the HIV+ patients presented with lipodistrophy, the majority of whom had hypertriglyceridemia. The HIV+ group had a higher percentage of fat mass (FM) and a lower percentage of fat-free mass (FFM) and cell mass (CM) than the control group measured by BIA. A high prevalence of dyslipidemia was found in the HIV+ group with higher mean total cholesterol, LDLcholesterol, and TG levels than in the control group. This prevalence was significantly higher in patients receiving PI, with increased levels of total cholesterol and LDL-cholesterol and a higher rate of alteration of the total cholesterol/HDL ratio. No differences were found in mean fasting glycemia, baseline insulin, or insulin resistance levels assessed using HOMA. In the HIV+ PI subgroup, increased carotid intima-media thickness was observed. Conclusion: In a group of vertically HIV-infected children on HAART, weight, height, percentage of FFM and CM were significantly lower and percentage of FM was significantly higher than in the control group. The high prevalence of dyslipidemia found in the HIV+ group, particularly in those exposed to PI, as well as the higher waist-to-height index increase the risk of developing ECVD (AU)

Uso de ezetimibe en el tratamiento de la hipercolesterolemia / Use of ezetimibe in the treatment of familial hypercholesterolemia in children and adolescents

La hipecolesterolemia familiar es el tipo de hiperlipidemia primaria hereditaria más frecuente y se asocia con una mayor prevalencia de enfermedad cardiovascular temprana. El ezetimibe reduce el LDL inhibiendo la absorción de esteroles en el enterocito. Objetivo: Mostrar nuestra experiencia en el uso de ezetimibe para el tratamiento de niños y adolescentes con hipercolesterolemia familiar heterocigota, en el corto y mediano plazo. M y M: Estudio longitudinal, retrospectivo, modelo antes-después donde cada paciente fue su propio control. Se incluyeron todos los pacientes que recibieron ezetimibe desde enero 2003 a diciembre 2009. Los pacientes cumplieron un período previo de 6 meses de dieta hipolipemiante y recomendaciones de actividad física. La eficacia se midió según la variación del LDL luego de3 meses de tratamiento. Se midieron los niveles de transaminasas y creatinfosfoquinasa antes y cada 3 meses durante el tratamiento. Se registraron los síntomas y efectos colaterales asociados con la administración de ezetimibe. Los pacientes que alcanzaron los objetivos terapéuticos continuaron con ezetimibe como monodroga, los que no, agregaron estatinas. Resultados: Se incluyeron 32 pacientes con edad media de 9,5 años (rango: 2-15,5). El tiempo total de seguimiento fue de 2,45 años (0,4-5,9 a). Luego de 3 meses de ezetimibe el LDL disminuyó un 25,7%. No se observaron efectos adversos durante el tratamiento como monoterapia. Al final del estudio, 11 pacientes habían agregado estatinas a su tratamiento por no haber alcanzado los objetivos. Conclusión: El ezetimibe resultó ser efectivo y seguro en niños y adolescentes con HF a corto y mediano plazo(AU)

Heterozygous familial hypercholesterolemia (FH) is the most common inherited type of primary hyperlipidemia. Patients with familial hypercholesterolemia have an increased level of LDL cholesterol since childhood, and present early associated cardiovascular disease. Ezetimibe reduces LDL by blocking sterol absorption in enterocytes. Aim: to show our experience on the use of ezetimibe in children and adolescents with familial hypercholesterolemia, with short and medium term follow-up. Patients and Methods: Retrospective and longitudinal study. Patients who were receiving ezetimibe as monotherapy from 2003 to 2009 were included. The primary efficacy parameter was the effect of ezetimibe on the LDL after three months of treatment. Serum levels of aspartate aminotransferase, alanine aminotransferase and creatine kinase were monitored. Patients were asked if they experienced any side effect with the ezetimibe treatment. If the Patients did not achieve therapeutical goals with ezetimibe as monotherapy a statin was added. Outcome at medium term follow-up is analysed. Results: The study included a total of 32 patients. The mean age at the start of ezetimibe was 9.5 years (range: 2 to 15.5). The mean total time of Ezetimibe was 2.45 years (r: 0.4 - 5.9).The decrease in mean LDL levels was -25.7%±12.3 or 59.5±34 mg% (P<.0001; 95% CI: 47.3-71.5, t test). There were no side effects with ezetimibe monotherapy. At the end of the study, 11patients required added statins due to failing to achieve the treatment goal. Conclusions: Ezetimibe is effective and safe for children and adolescents with FH in short and medium term follow-up(AU)

[Use of ezetimibe in the treatment of familial hypercholesterolemia in children and adolescents]. / Uso de ezetimibe en el tratamiento de la hipercolesterolemia.

UNLABELLED: Heterozygous familial hypercholesterolemia (FH) is the most common inherited type of primary hyperlipidemia. Patients with familial hypercholesterolemia have an increased level of LDL cholesterol since childhood, and present early associated cardiovascular disease. Ezetimibe reduces LDL by blocking sterol absorption in enterocytes. AIM: to show our experience on the use of ezetimibe in children and adolescents with familial hypercholesterolemia, with short and medium term follow-up. PATIENTS AND METHODS: Retrospective and longitudinal study. Patients who were receiving ezetimibe as monotherapy from 2003 to 2009 were included. The primary efficacy parameter was the effect of ezetimibe on the LDL after three months of treatment. Serum levels of aspartate aminotransferase, alanine aminotransferase and creatine kinase were monitored. Patients were asked if they experienced any side effect with the ezetimibe treatment. If the Patients did not achieve therapeutical goals with ezetimibe as monotherapy a statin was added. Outcome at medium term follow-up is analysed. RESULTS: The study included a total of 32 patients. The mean age at the start of ezetimibe was 9.5 years (range: 2 to 15.5). The mean total time of Ezetimibe was 2.45 years (r: 0.4 - 5.9).The decrease in mean LDL levels was -25.7% ± 12.3 or 59.5 ± 34 mg% (P<.0001; 95% CI: 47.3-71.5, t test). There were no side effects with ezetimibe monotherapy. At the end of the study, 11 patients required added statins due to failing to achieve the treatment goal. CONCLUSIONS: Ezetimibe is effective and safe for children and adolescents with FH in short and medium term follow-up.

Dynamics of range margins for metapopulations under climate change.

We link spatially explicit climate change predictions to a dynamic metapopulation model. Predictions of species' responses to climate change, incorporating metapopulation dynamics and elements of dispersal, allow us to explore the range margin dynamics for two lagomorphs of conservation concern. Although the lagomorphs have very different distribution patterns, shifts at the edge of the range were more pronounced than shifts in the overall metapopulation. For Romerolagus diazi (volcano rabbit), the lower elevation range limit shifted upslope by approximately 700 m. This reduced the area occupied by the metapopulation, as the mountain peak currently lacks suitable vegetation. For Lepus timidus (European mountain hare), we modelled the British metapopulation. Increasing the dispersive estimate caused the metapopulation to shift faster on the northern range margin (leading edge). By contrast, it caused the metapopulation to respond to climate change slower, rather than faster, on the southern range margin (trailing edge). The differential responses of the leading and trailing range margins and the relative sensitivity of range limits to climate change compared with that of the metapopulation centroid have important implications for where conservation monitoring should be targeted. Our study demonstrates the importance and possibility of moving from simple bioclimatic envelope models to second-generation models that incorporate both dynamic climate change and metapopulation dynamics.

Prospective analysis between the therapy of immunosuppressive medication and allogeneic microchimerism after liver transplantation.

After liver transplantation, migration of donor-derived hematopoietic cells to recipient can be detected in peripheral blood. This state is termed microchimerism. The aim of this study was to investigate prospectively the presence of allogeneic microchimerism, the occurrence of acute cellular rejection and the level of immunosuppression in transplanted patients. Microchimerism occurrence between 10 days and 12 months after liver transplantation was analyzed in 47 patients aged between 15 and 65 by a two-stage nested PCR/SSP technique to detect donor MHC HLA-DR gene specifically. A pre-transplant blood sample was collected from each patient to serve as individual negative control. Microchimerism was demonstrated in 32 (68%) of the 47 patients; of these, only 10 patients (31.2%) presented rejection. Early microchimerism was observed in 25 patients (78.12%) and late microchimerism in 7 patients (21.8%). Among the patients with microchimerism, 14 were given CyA and 18 were given FK506. In the group without microchimerism, 12 patients were given CyA and 03 were given FK506. There was a significant association between the presence of microchimerism and the absence of rejection (p=0.02) and also between microchimerism and the type of immunosuppression used. Our data indicate that microchimerism and probably differentiation of donor-derived leukocytes can have relevant immunologic effects both in terms of sensitization of recipient and in terms of immunomodulation toward tolerance induction.

Scale effects and human impact on the elevational species richness gradients.

Despite two centuries of effort in characterizing environmental gradients of species richness in search of universal patterns, surprisingly few of these patterns have been widely acknowledged. Species richness along altitudinal gradients was previously assumed to increase universally from cool highlands to warm lowlands, mirroring the latitudinal increase in species richness from cool to warm latitudes. However, since the more recent general acceptance of altitudinal gradients as model templates for testing hypotheses behind large-scale patterns of diversity, these gradients have been used in support of all the main diversity hypotheses, although little consensus has been achieved. Here we show that when resampling a data set comprising 400,000 records for 3,046 Pyrenean floristic species at different scales of analysis (achieved by varying grain size and the extent of the gradients sampled), the derived species richness pattern changed progressively from hump-shaped to a monotonic pattern as the scale of extent diminished. Scale effects alone gave rise to as many conflicting patterns of species richness as had previously been reported in the literature, and scale effects lent significantly different statistical support to competing diversity hypotheses. Effects of scale on current studies may be affected by human activities, because montane ecosystems and human activities are intimately connected. This interdependence has led to a global reduction in natural lowland habitats, hampering our ability to detect universal patterns and impeding the search for universal diversity gradients to discover the mechanisms determining the distribution of biological diversity on Earth.

Molecular mechanisms associated with donor-specific microchimerism in peripheral blood of Brazilian patients after liver transplantation.

A large number of studies in liver transplantation have demonstrated allogeneic microchimerism. The clinical and immunologic implications of this finding remain inconclusive, just as the influence of HLA mismatch and donor alloreactivity also are controversial. The present study analyzed the presence of allogeneic microchimerism in liver transplant recipients in relation to donor leukocyte kinetics and rejection episodes. The study was extended to determining the influence of immunogenetic factors in patients after liver transplantation. The presence of allogeneic microchimerism was analyzed on peripheral blood of 50 recipients. DNA extracted from the samples was subjected to typing for HLA-DRB1 and -DQB1 alleles by polymerase chain reactions using sequence-specific primers (PCR/SSP). Microchimerism was identified by nested PCR/SSP. Microchimerism was detected in 72% of patients. There was significant effect of microchimerism on rejection episodes (P=.002), while HLA mismatches did not show significance for one or two mismatches (P=.98). Allogeneic microchimerism detected in the majority of liver transplant patients was observed to be significantly associated with rejection episodes.

Evaluación del estado nutricional en una población de niños internados en el Hospital Garrahan / Nutritional assessment of children hospitalized in Garrahan Pediatric Hospital

La malnutrición en la población hospitalizada se asocia con aumento de la mortalidad, complicaciones médicas, prolongación de la hospitalización y mayores costos. El objetivo del presente estudio fue conocer la prevalencia de malnutrición aguda y crónica en la población hospitalizada e identificar factores asociados. El estudio fue un corte transversal,, que incluyo a todos los pacientes internados en las salas de cuidados intermedios y moderados durante la semana del 12 al 19 de mayo del 2003. El diagnóstico nutricional se basó en métodos antropométricos, aplicando la clasificación de Waterloo modificada. La evaluación incluyó una encuesta administrada por el mismo médico que realizó la antropometría con datos de filiación y procedencia y con información sobre nivel de educación y actividad laboral de los padres, características de la vivienda , número de habitantes por cuarto, ingresos económicos, beneficios de planes sociales y cobertura social. Resultados: Fueron evaluados 198 pacientes con una edad media de 5,2 años más o menos 5, el 42,5% de los pacientes con compromiso nutricional: 19% malnutridos emaciados, 7,9% acortados y emaciados, 15,6% acortados y sobrepeso u obesidad el 11,7% de la población. De los niños con deficit de peso/talla (total 26,9%), el 12, 3% presentó un deficit leve, el 11,2% moderado y el 3,4% grave. 1 de acuerdo al nivel de ingreso las familias se clasificaron como indigentes (ingreso menor de $ 330 ): 43%; pobres (ingreso menor de $ 724) 37%; y con necesidades básicas satisfechas 20%. No se encontró asociación con variables sociales. Las variables biológicas que se asociaron con mayor frecuencia de malnutrición fueron la edad (p=0,04), la condición de cronocidad (p<0,01), y la duración de la internación mayor de 25 días (p=0.04%). En el subgrupo de pacientes evaluados co menos de 5 días de internados conpatologías agudas la frecuencia de malnutridos emaciados fue de 12,6%, de acortados 18,2, normales 60,6%, sobrepeso 9%.

Development of donor-specific microchimerism in liver transplant recipient with HLA-DRB1 and -DQB1 mismatch related to rejection episodes.

Migration of donor-derived cells to recipient tissues after liver transplantation has been suggested as a mechanism to induce and maintain allograft tolerance, although important issues remain including acute rejection posttransplantation mortality, and complications related to immunosuppressive therapy. We therefore examined the relation of rejection to chimerism based upon recipient and donor mismatch of HLA-DRB1 and -DQB1 alleles. Laboratory analysis of peripheral blood was performed before and 10 days to 16 months after liver transplantation in 32 recipients, using ganglion or spleen cell samples of respective donors. DNA was extracted for HLA-DRB1 and DQB1 allele typing using polymerase chain reactions with sequence-specific primers (PCR-SSP). Microchimerism was analyzed through nested PCR. Our results confirmed that patients with one or two mismatched HLA-DRB1 and-DQB1 alleles showed microchimerism and no rejection (P <.05). Microchimerism was present in 71.88% of the patients, and a significant association of rejection P <.05 was found when microchimerism was correlated to graft rejection. These results suggest that the presence of microchimerism may be associated with acceptance, tolerance and survival of the allograft.

Electron spin-relaxation via vibronic level of nickel (I) and nickel (III) cyanide complexes in NaCl single crystals.

Electron spin-lattice relaxation rates for the low spin [Ni(CN)(4)](1-) and [Ni(CN)(4)](3-) complexes in NaCl host lattice were measured by the inversion recovery technique in the temperature range 7-50K. The data for both paramagnetic species fit very well to a relaxation process involving localized anharmonic vibration modes, also responsible for the g-tensor temperature dependence.

Evaluación de un programa de educación de tratamiento intensivo en adolescentes con diabetes tipo 1. Seguimiento por dos años / Evaluation of an intensive treatment education program for type 1 diabetes in a group of adolescents. A two year follow up

During the past decade several reports were published showing that intensive treatment of type 1 diabetes can prevent and delay disease-related microvascular complications. However, several problems were reported in children and adolescents such as frequent hypoglycemic episodes and weight gain. The aim of this study was to describe the results of intensified treatment for type 1 diabetes in a group of Argentinean adolescents after a follow-up of two years. Twenty five adolescents with type 1 diabetes older than 10 years with at least one year from diagnosis were selected. All patients received a one-week teaching program during admission to our center. All patients were followed-up monthly during two years. Treatment schedule included 4-5 controls in fasting conditions, two doses of NPH insulin and four doses of regular insulin according to glycemia and the amount of calculated carbohydrate intake. Median age was 13.5 years (range 10 to 19 years). Mean time from diagnosis to inclusion in the study was 3.8 years (range 1.25 to 9 years). Mean total dose of NPH insulin decreased significantly when measured at the inclusion in the study (0.9 IU/kg) and after a year of follow-up 0.8 IU/kg (p 0.04). However, there were no changes in NPH insulin dose after two years follow-up (0.85 IU/kg). On the contrary, the dose of regular insulin administered on fasting conditions with normal glycemia increased from 0 to 0.21/kg after a year (p 0.0001) and to 0.69 after two years (non significant). Median HbA1C showed a significant reduction from 10 +/- 1.62% to 8.53 +/- 1.04% after a year (p 0.03) and to 8.72 +/- 0.81% after two years. BMI Z score increased from significantly from 0.7 +/- 0.9 to 1.06 +/- 1.15 after a year (p 0.03) with a further reduction without a significant difference from the basal value after two years. We found no significant differences in the frequency of hypoglycemia or other metabolic features. Our results show that intensive treatment of type 1 diab...

Durante la década pasada, se publicaron numerosos trabajos demostrando que el tratamiento intensivo de la diabetes tipo 1 puede prevenir y retrasar el desarrollo de las complicaciones microvasculares asociadas a la misma. Sin embargo en el grupo de niños y adolescentes se hallaron algunos problemas como el incremento de la frecuencia de los episodios de hipoglucemia y el excesivo aumento de peso. El propósito del presente estudio fue describir los resultados del tratamiento intensificado llevado a cabo durante 2 años en una población de niños y adolescentes argentinos con diabetes tipo 1. Fueron seleccionados 25 pacientes mayores de 10 años de edad con diabetes de más de 1 año de evolución. Todos ellos realizaron un programa de educación durante una semana de internación. El seguimiento posterior fue mensual durante los siguientes dos años. El esquema de tratamiento insulínico consistió en 4 a 5 controles preprandiales diarios, dos dosis de insulina NPH cubriendo requerimientos basales y cuatro dosis de insulina regular preprandial ajustadas de acuerdo al cálculode hidratos de carbono a ingerir, la actividad física y el valor de glucemia. La media de edad fue de 13.5años (r: 10-19 años). El tiempo medio transcurrido desde el diagnóstico hasta la intensificación del tratamientofue de 3.8 años ( r: 1.2 –9 años). La dosis media total de NPH disminuyó significativamente desde 0.9 U/kg en elinicio a 0.8 U/kg al año de seguimiento (p = 0.04), sin diferencias al segundo año de seguimiento (0.85 U/kg). Porel contrario, la dosis de insulina regular administrada en forma preprandial en normoglucemia aumentó de 0 a0.21 U/kg en el primer año (p 0.0001) y a 0.69 U/kg a los dos años (p NS). La media de HbA1C mostró unasignificativa reducción desde 10±1.62% a 8.53±1.04% en el primer año (p = 0.03) y 8.72± 0.81% a los dos años.El Z score de IMC aumentó significativamente de 0.7 ± 0.9 a 1.06 ± 1.15 luego de un año (p = 0.03) descendiendo a valores no...

Evaluación de un programa de educación de tratamiento intensivo en adolescentes con diabetes tipo 1. Seguimiento por dos años / Evaluation of an intensive treatment education program for type 1 diabetes in a group of adolescents. A two year follow up

During the past decade several reports were published showing that intensive treatment of type 1 diabetes can prevent and delay disease-related microvascular complications. However, several problems were reported in children and adolescents such as frequent hypoglycemic episodes and weight gain. The aim of this study was to describe the results of intensified treatment for type 1 diabetes in a group of Argentinean adolescents after a follow-up of two years. Twenty five adolescents with type 1 diabetes older than 10 years with at least one year from diagnosis were selected. All patients received a one-week teaching program during admission to our center. All patients were followed-up monthly during two years. Treatment schedule included 4-5 controls in fasting conditions, two doses of NPH insulin and four doses of regular insulin according to glycemia and the amount of calculated carbohydrate intake. Median age was 13.5 years (range 10 to 19 years). Mean time from diagnosis to inclusion in the study was 3.8 years (range 1.25 to 9 years). Mean total dose of NPH insulin decreased significantly when measured at the inclusion in the study (0.9 IU/kg) and after a year of follow-up 0.8 IU/kg (p 0.04). However, there were no changes in NPH insulin dose after two years follow-up (0.85 IU/kg). On the contrary, the dose of regular insulin administered on fasting conditions with normal glycemia increased from 0 to 0.21/kg after a year (p 0.0001) and to 0.69 after two years (non significant). Median HbA1C showed a significant reduction from 10 +/- 1.62% to 8.53 +/- 1.04% after a year (p 0.03) and to 8.72 +/- 0.81% after two years. BMI Z score increased from significantly from 0.7 +/- 0.9 to 1.06 +/- 1.15 after a year (p 0.03) with a further reduction without a significant difference from the basal value after two years. We found no significant differences in the frequency of hypoglycemia or other metabolic features. Our results show that intensive treatment of type 1 diab...(AU)

Durante la década pasada, se publicaron numerosos trabajos demostrando que el tratamiento intensivo de la diabetes tipo 1 puede prevenir y retrasar el desarrollo de las complicaciones microvasculares asociadas a la misma. Sin embargo en el grupo de niños y adolescentes se hallaron algunos problemas como el incremento de la frecuencia de los episodios de hipoglucemia y el excesivo aumento de peso. El propósito del presente estudio fue describir los resultados del tratamiento intensificado llevado a cabo durante 2 años en una población de niños y adolescentes argentinos con diabetes tipo 1. Fueron seleccionados 25 pacientes mayores de 10 años de edad con diabetes de más de 1 año de evolución. Todos ellos realizaron un programa de educación durante una semana de internación. El seguimiento posterior fue mensual durante los siguientes dos años. El esquema de tratamiento insulínico consistió en 4 a 5 controles preprandiales diarios, dos dosis de insulina NPH cubriendo requerimientos basales y cuatro dosis de insulina regular preprandial ajustadas de acuerdo al cálculode hidratos de carbono a ingerir, la actividad física y el valor de glucemia. La media de edad fue de 13.5años (r: 10-19 años). El tiempo medio transcurrido desde el diagnóstico hasta la intensificación del tratamientofue de 3.8 años ( r: 1.2 ¹9 años). La dosis media total de NPH disminuyó significativamente desde 0.9 U/kg en elinicio a 0.8 U/kg al año de seguimiento (p = 0.04), sin diferencias al segundo año de seguimiento (0.85 U/kg). Porel contrario, la dosis de insulina regular administrada en forma preprandial en normoglucemia aumentó de 0 a0.21 U/kg en el primer año (p 0.0001) y a 0.69 U/kg a los dos años (p NS). La media de HbA1C mostró unasignificativa reducción desde 10±1.62% a 8.53±1.04% en el primer año (p = 0.03) y 8.72± 0.81% a los dos años.El Z score de IMC aumentó significativamente de 0.7 ± 0.9 a 1.06 ± 1.15 luego de un año (p = 0.03) descendiendo a valores no...(AU)

Autonomic dysfunction in Chagas disease: lack of participation of the vagus nerve.

To evaluate the possible role of the vagus nerve in the development of the dysautonomia in Chagas disease, we examined 18 nerves from chagasic patients and 8 from non-chagasic patients, autopsied at the Department of Pathology, Ribeirão Preto School of Medicine, Brazil. Histological analysis showed mild inflammatory infiltrate composed predominantly of T lymphocytes, in epi-, peri- and endoneurium. No parasites were observed. Semithin sections showed swollen unmyelinated fibres, occasional thinly myelinated fibres, degenerated and atrophic axons, related to myelinated fibres. These findings were confirmed by electron microscopy, and in teased fibres. The changes were observed both in chagasic and in non-chagasic patients. Statistical analysis of the morphometric findings (myelinated fibre density, axonal and fibre diameters) failed to show significant differences between the 2 groups. The frequency of myelinated fibres of various diameters was also similar in the 2 groups. The morphological and morphometrical findings in chagasic patients are mild, non-specific, and could be related to the age of the patients, or with artefacts, since they have also been observed in non-chagasic patients. Retrograde changes due to the ganglionic lesions in the innervated organs cannot be completely ruled out. Our results do not allow us to implicate the vagus nerve in the dysautonomia in Chagas disease.

Using probability of persistence to identify important areas for biodiversity conservation.

Most attempts to identify important areas for biodiversity have sought to represent valued features from what is known of their current distribution, and have treated all included records as equivalent. We develop the idea that a more direct way of planning for conservation success is to consider the probability of persistence for the valued features. Probabilities also provide a consistent basis for integrating the many pattern and process factors affecting conservation success. To apply the approach, we describe a method for seeking networks of conservation areas that maximize probabilities of persistence across species. With data for European trees, this method requires less than half as many areas as an earlier method to represent all species with a probability of at least 0.95 (where possible). Alternatively, for trials choosing any number of areas between one and 50, the method increases the mean probability among species by more than 10%. This improvement benefits the least-widespread species the most and results in greater connectivity among selected areas. The proposed method can accommodate local differences in viability, vulnerability, threats, costs, or other social and political constraints, and is applicable in principle to any surrogate measure for biodiversity value.

Fungal infections.

Fungal infections have increased in frequency in the last decades because of the growing number of immunocompromised patients who survive longer periods of time than in the past, the widespread use of immunosuppressive drugs, a large aging population with increased numbers of malignancies, and the spread of AIDS. Although fungi are present everywhere, some mycoses predominate in the tropics, not only in view of warm temperature and humid climate, which favor their growth, but also because of inadequate hygienic and working conditions brought about by poverty. Mycotic diseases in the brain are usually secondary to infections elsewhere in the body, usually the lungs, less often from other extracranial sites, and in the vast majority of the cases spread via blood circulation. Only occasionally they result from direct extensions from infections of the sinuses or bone, and less frequently from prosthetic heart valves. Candida may be endogenous in origin, inhabiting the digestive tract. Most fungi cause basal meningitis or intraparenchymal abscesses. Direct extension from the cribriform plate cause necro-hemorrhagic lesions in the base of the frontal lobe. Although fungi are common in our environment, few are pathogenic. In this paper mycotic infections are divided into opportunistic and pathogenic; although most of the latter have also been described in immunosuppressed patients, some of those caused by opportunistic organisms, have also occurred in the absence of predisposing factors.

Strength deficit of knee extensor muscles of individuals with Down syndrome from childhood to adolescence.

The isokinetic strength of the knee extensor muscles of both limbs, at the speed of 30 degrees/second, was evaluated in 25 children and adolescents with Down syndrome. Comparison with two control groups of 40 intellectually average individuals and 30 individuals with mental retardation of unknown origin showed that both children and adolescents with Down syndrome were weaker than were the control subjects. Moreover, by the age of 14 years, adolescents with Down syndrome failed to show the muscle strength increase that physiologically occurs by this age. Interlimb comparison of knee extensor muscles showed a strength dominance in the 44% of individuals with Down syndrome, with a prevalence for the left leg. In conclusion, our data suggest the presence of a dysfunction of the neuromuscular system both at the level of the pyramidal system and/or of the neuromuscular junction, possibly as an expression of premature ageing.

Possible role of an adrenal parasite reservoir in the pathogenesis of chronic Trypanosoma cruzi myocarditis.

The possible contribution of parasitism of the central vein of the adrenal gland (CVAG) to chronic Trypanosoma cruzi myocarditis was assayed by comparing the occurrence of nests of amastigotes in the left ventricular myocardium (LVM) and determining the number and extent of areas of focal leucocyte exudate (FLE) in Chagas disease patients with and without CVAG parasitism. The frequency of occurrence of T. cruzi nests in the LVM, as well as the FLE number and area, were greater among patients with CVAG parasitism. We therefore suggest that CVAG parasitism plays a role in the onset and intensity of chronic T. cruzi myocarditis.