[Tuberculosis: the counterpoint of progress]. / Tuberculosis: el contrapunto del progreso.

Along history, infectious diseases have had a direct influence in the development of humanity, with tuberculosis showing a leading role. Despite this disease being the main cause of mortality among infectious diseases, it remains neglected and constitutes a serious public health problem, especially among the poorest countries in the world. Tuberculosis greatest importance goes beyond Medicine, and a holistic view of the disease allows us to comprehend the economic and social development of a nation. Despite a historically successful control program in Chile, current figures are not auspicious and force upon us the need to address this problem with a multidisciplinary approach. The medical physician is required to put again into practice the fundamental principle of Medicine, Semiology to contribute to the control of tuberculosis.

Relationship of type 1 diabetes to ancestral proportions and HLA DR/DQ alleles in a sample of the admixed Cuban population.

BACKGROUND: Incidence of type 1 diabetes varies widely around the world, probably due to ethnic differences across populations among other factors. AIMS: To determine whether there is an association between disease and ancestry proportions; and to control disease-HLA associations for possible confounding by admixture or population stratification. SUBJECTS AND METHODS: 100 cases and 129 controls participated in the study. Ancestry informative markers, which have considerable differences in frequency between European, West African and Native American populations were used. Type 1 diabetes associated HLA susceptibility/protection alleles were ascertained by PCR using specific primers. Statistical analyses were conducted using STRUCTURE 2.1, ADMIXMAP 3.7, SPSS 16.0 and STRAT 1.0 packages. RESULTS: The results of logistic regression implemented in ADMIXMAP 3.7 indicated that European ancestry was associated with type 1 diabetes mellitus with an odds ratio of 5.7 corresponding to one unit change in European admixture proportion. Association was found between HLA alleles and disease, DQA1*0501, *0301 DQB1*0201 and DRB1*0301, *0401 being susceptibility alleles and DRB1*1501, DQA1*0102/3 and DQB1*0602 being protective alleles. CONCLUSIONS: We found an association between European ancestry and type 1 diabetes in our sample, indicating the contribution of ethnicity to incidence differences. Previously reported associations of HLA DR/DQ alleles with disease are confirmed for the admixed Cuban population.

Tuberculosis: el contrapunto del progreso / Tuberculosis: the counterpoint of progress

Resumen A lo largo de la historia, las enfermedades infecciosas han influido directamente en el desarrollo de la humanidad y en este proceso, la tuberculosis ha tenido un rol protagónico. Esta enfermedad mata más seres humanos que cualquier otra de causa infecciosa y, a pesar de esto, continúa siendo una entidad olvidada y un grave problema de salud pública, sobre todo en las naciones más pobres. La trascendencia de la tuberculosis va más allá del ámbito médico y una visión holística de ella nos permite comprender el grado de desarrollo económico y social de un Estado. Si bien Chile mantenía un programa de control históricamente exitoso, las cifras actuales no son auspiciosas y obligan a analizar el problema desde una mirada multidisciplinaria. Es en este marco que planteamos que el médico clínico, para aportar en el control de la enfermedad, debe poner nuevamente en práctica uno de los principios básicos de la Medicina: la semiología.

Abstract Along history, infectious diseases have had a direct influence in the development of humanity, with tuberculosis showing a leading role. Despite this disease being the main cause of mortality among infectious diseases, it remains neglected and constitutes a serious public health problem, especially among the poorest countries in the world. Tuberculosis greatest importance goes beyond Medicine, and a holistic view of the disease allows us to comprehend the economic and social development of a nation. Despite a historically successful control program in Chile, current figures are not auspicious and force upon us the need to address this problem with a multidisciplinary approach. The medical physician is required to put again into practice the fundamental principle of Medicine, Semiology to contribute to the control of tuberculosis.

Effect of standard nicotinamide in the prevention of type 1 diabetes in first degree relatives of persons with type 1 diabetes.

BACKGROUND: Nicotinamide has been used with success to prevent type 1 diabetes in animal models and humans. This vitamin B3 derivative has attracting effects on beta-cell protection and regeneration. AIM/HYPOTHESIS: To evaluate the effect of standard nicotinamide administration on type 1 diabetes prevention in first degree relatives of persons with type 1 diabetes as well as on the concentrations of islet-cell-related autoantibodies, insulin secretion and peripheral sensitivity. SUBJECTS AND METHODS: A randomized double-blind placebo controlled intervention trial was conducted in 40 first degree relatives of type 1 diabetic patients. Persistence of ICA ( >or= 10 JDF units) was among inclusion criteria. Participants were randomly allocated oral standard nicotinamide (1.2 g/m2) or placebo for 5 years. Groups were also stratified by age. Islet associated antibodies, fasting blood glucose, fasting plasma insulin concentrations, OGTT, IVGTT and HLA-DR genotyping were performed in all participants. The main criterion to stop treatment was type 1 diabetes development as defined by WHO. RESULTS: Type 1 diabetes development frequencies were similar between the treatment groups. ICA frequencies at the end of the study, first phase insulin release, and insulin sensitivity did not differ between groups as well. None of the participants suffered from any adverse events described for nicotinamide. CONCLUSIONS: Type 1 diabetes prevention trial using standard nicotinamide is feasible but fails to prevent or delay the disease onset at the dose we used.

Slowly progressing type 1 diabetes: persistence of islet cell autoantibodies is related to glibenclamide treatment.

BACKGROUND: Several experimental studies in rats have demonstrated that sulfonylurea treatment increases autoantigen expression in B-cells. This phenomenon may be deleterious for the preservation of residual beta cell function in patients with slowly progressing type 1 diabetes or latent autoimmune diabetes of adult (LADA). AIM/HYPOTHESIS: The aim of the present study was to evaluate whether the exclusion of glibenclamide in the treatment of ICA positive type 2 diabetic patients may diminish or halt the humoral autoimmune response against B-cells as well as improve metabolic control and insulin secretion. SUBJECTS AND METHODS: Fourteen type 2 diabetic patients with pancreatic autoimmunity (ICA+ and GABA+) and treated with insulin and glibenclamide (duration of disease 2.0 +/- 2.2, range 0.1-7 years and age 53 +/- 12.5, range 36-75 years) were studied. Patients were randomly assigned to two treatment groups, Group 1: insulin monotherapy (n = 8, age 53 +/- 6.4 years) (Exclusion of glibenclamide) and, Group 2: insulin plus glibenclamide (n = 6, age 53.5 +/- 16.9) (Unmodified treatment). Both groups were investigated at the beginning of the study and after one year for the following parameters: ICA and anti-GAD65 antibodies, fasting glucose and fasting C-peptide. RESULTS: In group 1, six out of eight patients became ICA negative while all patients in group 2 remained ICA positive (p = 0.0097). Fasting glucose concentrations improved in group 1 (4.6 +/- 2.8) in relation to group 2 (11.5 +/- 5.5, p = 0.0023) after one year of treatment. No differences were found for anti-GAD antibodies and fasting C-Peptide between the groups. CONCLUSIONS: These data show that exclusion of glibenclamide in the treatment of ICA+ type 2 diabetic patients partially decreases specific autoimmunity against endocrine pancreatic cells and improves metabolic control. This may reflect decreased expression of B-cell autoantigens suggesting that insulin monotherapy is a better choice for the treatment of LADA.

First-degree relatives of persons with type 1 diabetes: insulin resistance and enterovirus infection are associated with different patterns of islet cell autoimmunity.

Type 1 diabetes (T1D) results from the interaction of genetic and environmental factors. Previous studies indicate an association between detection of Enterovirus (EV) genome in blood and the clinical onset of T1D. Insulin resistance can also represent a risk factor for progression to clinically overt T1D. This study aimed at evaluating whether there is association between both EV infection and insulin resistance with islet autoantibodies in first-degree relatives of persons with type 1 diabetes. We collected sera from 94 first-degree relatives with (32) or without (64) islet cell antibodies (ICA) from the Cuban T1D prediction program. Blood glucose and insulin concentrations were determined. Antibodies to GAD65 and IA-2 were determined by radioimmunoassay. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). EV-RNA was detected in serum using a highly sensitive reverse transcriptase-polymerase chain reaction method. The occurrence of EV-RNA was higher in ICA-positive relatives than in ICA-negative ones [15.6% (5/32) vs. 1.6% (1/62), P = 0.016]. GAD65 autoantibodies were more frequent in subjects with insulin resistance [34.5% (10/29) vs. 13.9% (9/65), P = 0.028] as defined by the HOMA-IR value. GAD65 autoantibodies also positively correlated with HOMA-IR (r.bis = 0.28, P < 0.01). IA-2 autoantibodies did correlate neither with EV-RNA nor with insulin resistance. There was no association between the presence of EV-RNA and insulin resistance. Our data suggest that enterovirus infection and insulin resistance are two independent events associated with ICA and GAD65 autoantibodies, respectively. These observations support the multifactorial nature of T1D.

Occurrence of enterovirus RNA in serum of children with newly diagnosed type 1 diabetes and islet cell autoantibody-positive subjects in a population with a low incidence of type 1 diabetes.

BACKGROUND: The penetrance of type 1 diabetes mellitus (T1DM) in a genetically susceptible population is largely determined by environmental influences amongst which the human enteroviruses are prominent putative factors. AIM/HYPOTHESIS: The aim of this study was to determine the occurrence of enterovirus RNA in serum of children with type 1 diabetes at onset and ICA-positive subjects in a population with low incidence of type 1 diabetes and high circulation of enteroviruses. SUBJECTS AND METHODS: Serum samples were collected from children with newly diagnosed type 1 diabetes (n = 34); islet autoantibody-positive (n = 32) and -negative (n = 31) first-degree relatives of type 1 diabetic patients; and control subjects (n = 194). Enteroviral RNA was assessed using a highly sensitive reverse transcriptase-polymerase chain reaction method. RESULTS: The frequency of positive signals corresponding to enteroviral sequence amplifications were higher in newly diagnosed T1DM children (9/34, 26.5%) and islet autoantibody-positive first-degree relatives (5/32, 15.6%) than in their corresponding matched controls (2/68, 2.9%, p = 0.0007 and 0/64, 0.0%, p = 0.0033, respectively). The presence of enteroviral RNA appeared to be associated with severe diabetic ketoacidosis at onset (pH < 7.1, p = 0.0328) and high ICA titres ( > or = 20 JDF units, p < 0.05). CONCLUSIONS: Despite there is a high circulation of enteroviruses and a low type 1 diabetes incidence in the Cuban population, the presence of enteroviral RNA is associated with type 1 diabetes and beta-cell autoimmunity and is similar to European countries in which this scenario is reversed.

Islet cell related antibodies and type 1 diabetes associated with echovirus 30 epidemic: a case report.

Type 1 diabetes associated genes account for less than 50% of disease susceptibility. Human enteroviruses have been implicated as environmental factors that might trigger and/or accelerate this autoimmune disorder. We now report of a 12-year-old girl that developed pancreatic autoimmunity and type 1 diabetes after enteroviral infection. Diabetes-associated autoimmunity was evaluated by measurement of several islet cell related autoantibodies. Neutralizing antibodies to different enteroviruses were determined in the case and eight children suffering from aseptic meningitis during a large scale epidemic. Several types of diabetes-associated antibodies were detected post-infection in the adolescent with newly diagnosed type 1 diabetes, including islet cell antibodies (ICA) and tyrosine phosphatase antibodies (IA2A). ICA but not IA2A appeared in the non-diabetic enterovirus-infected subjects. Based on virological studies, type 1 diabetes pathogenesis process could have been triggered by echovirus 30 infections. This study provides the first evidence of an association between echovirus 30 infection with the presence of pancreatic autoimmunity and type 1 diabetes. Our data suggest that echovirus 30 Cuban strain could be considered a potentially diabetogenic enteroviral variant.

Características de los anticuerpos antiislotes del adulto, diabético tipo I de reciente diagnóstico, familiares de primer grado de diabéticos tipo 1 y diabetes gestacional / ICA characteristics in latent autoimmune diabetes of adults, new onset type diabetics, first degree relatives of type l diabetics and gestational diabetes

Se estudiaron las características de los sueros con anticuerpos antiislotes pancreáticos (ICA+) títulos, ICA sobre páncreas de ratón (ICA-NR), reactividad a extractos glucolipídicos pancreáticos (REGP) y asociación a anticuerpos anti-GAD65) en diferentes grupos de sujetos: diabetes autoinmune del adulto (LADA, n = 20), diabéticos tipo 1 de reciente diagnóstico (DMIDrd, n = 43), familiares de primer grado de diabéticos tipo 1 (FPG, n = 31) y mujeres con diabetes gestacional (DG, n = 10). Se detectaron ICA e ICA-NR por la técnica de inmunofluorescencia indirecta y los anticuerpos anti-GAD65, por un método RIA de inmunoprecipitación. Se utilizó la fase superior de extractos pancreáticos humanos que contienen glucolípidos para medir REGP de los ICA. Se determinaron las características de los ICA en los diferentes grupos: LADA: alta frecuencia en sus títulos (ü 80 unidades JDF) (80 porciento), anticuerpos anti-GAD65 (100 porciento) y baja frecuencia de ICA-NR (15 porciento) y REGP (15 porciento); DMIDrd: alta frecuencia de anticuerpos anti-GAD65 (72 porciento), ICA-NR (81 porciento) y REGP (86 porciento); FPG: alta frecuencia de ICA-NR (93 porciento) y REGP (87 porciento); DG: Bajos títulos de ICA (< 20 unidades JDF) (60 porciento) y alta frecuencia de REGP (80 porciento), aunque la REGP fue generalmente parcial. Se comprobó que en los grupos estudiados, el proceo de pérdida de la tolerancia inmunológica es disímil porque los ICA reconocen a determinantes antigénicos diferentes. Estos resultados son también importantes para seleccionar el marcador inmunológico correcto para la predicción del proceso autoinmune en cada entidad(AU)

Seguimiento clínico de la diabetes mellitus tipo II con títulos de anticuerpos antiislotes (ICA) con diferentes tiempos de evolución de la enfermedad / Clinical follow-up of diabetes mellitus type II with antiislet antibody titers with different lengths of duration of the disease

Se estudiaron 74 diabéticos tipo II mayores de 35 años. Para la determinación del ICA se utilizó el método de inmunofluorecencia indirecta sobre cortes de páncreas humanos fijados en reactivo Bouin en parafina. El 41,89 de los pacientes tuvieron ICA. Su frecuencia fue menor cuando el tiempo de evolución era mayor de 15 años. No hubo diferencias significativas en relación con el tiempo de evolución promedio entre los casos con ICA o sin ellos. Los antecedentes familiares de diabetes no influyeron significativamente en la presencia o ausencia de ICA. La retinopatía fue más frecuente en los sujetos con ICA negativos. En relación con los niveles de glicemia, colesterol, triglicéridos y HDL-c solo comprobamos una tendencia a ser mayores los valores de HDL-c en los diabéticos que no tenían ICA. Del total de pacientes con ICA sólo el 13,80% tenía un buen control metabólico. a diferencia de los que no los tenian en quienes se observó en el 34.1% (p<0.05). La dieta era utilizada por 9 pacientes y los compuestos orales hipoglicemiantes por 10. Es llamativo que de un total de 27 pacientes que empleaban insulina , 19 de ellos tenían ICA. De nuestro trbajo podemos concluir que: los diabéticos con ICA presentan más dificultades en lograr un buen control metabólico y que la mayoría de los mismos son tributarios de necesitar tratamiento insulínico en algún momento de su evolución para lograr un buen control metabólico. Es probable que la presencia de ICA en los diabéticos tipo II se indicador de un posible tratamiento insulínico en algún momento de su evolución

Distribución de los antígenos HLA-DR en diabéticos tipo II en Cuba y su relación con los anticuerpos citoplasmáticos insulares / Distribution of HLA-DR antigens in type II diabetics in Cuba and its association with insular cytoplasmatic antibodies

Se comprobó que en la población diabética tipo II en Cuba existe una asociación positiva con el antígeno HLA-DR y una negativa con el HLA-DR2 . Si tomamos en cuenta la presencia o no de la ICA en estos enfermos vemos que los ICA negativos no difieren de la población diabética tipo II en general, en lo referido a su frecuencia fenotípica HLA-DR. sin embargo , los ICA positivos presentan un aumento significativo del antígeno HLA-DR4, con respecto a la población no diabética. Se concluye que el tipaje para los antígenos HLA-DR permitiría anticipar en el momento del diagnóstico, aquellos pacientes diabéticos tipo II, con mayor riesgo de presentar dificultades en el mantenimiento de un buen control metabólico, con ayuda de los tratamientos hipoglicemiantes orales convencionales

Estudio prospectivo en niños con alto riesgo de diabetes tipo I como secuela de infección por virus ECHO-4: 1986-1989 / Prospective study in children with high risk of type I diabetes as a sequel of ECHO-4 virus infection: 1986-1989

El estudio comprendió 111 niños enfermos y como controles se utilizaron muestras de suero de niños hospitalizados en el mismo período por causas no endocrinológicas. El agente patogénico fue identificado como un virus EHO-4 en el Instituto de Higiene y Epidemiología. Se comprobó que el 10 % de los niños presentaban intolerancia previa a la glucosa, el 17 % tenía valores alterados de la hemoglobina glicosilada (>8,00) y el 65 %, alteraciones de la inmunidad humoral y/o celular panereatoespecíficas, lo cual les confiere el status de alto riesgo de padecer de diabetes tipo I. Se realiza el primer informe en el ámbito internacional, sobre la importancia de las infecciones por virus ECHO como fator de riesgo de diabetes mellitus insulinodependiente (DMID,tipo I) y se alerta a nuestras autoridades sanitarias con el fin de que se tomen medidas para su prevención y erradicación

Detección de anticuerpos antiinsulina por un método inmunoenzimático (MicroELISA) / Detection of anti-insuline antibodies by inmunoenzymatic method (microELISA)

Se realizò el montaje de un método inmunoenzimático (ELISA) para la detección de anticuerpos capaces de reconocer la molécula de insulina y se aplicó a un grupo de 130 sujetos normales; se escogió el valor límite de negatividad para el ensayo y se aplicó a la población estudiada de diabéticos. Los coeficientes de variación obtenidos se hallan dentro del rango de valores normales para este procedimiento. No se observó correspondencia total entre los resultados de las muestras evaluadas con este método y el isotópico convencional empleado en el Instituto Nacional de Endocrinología. Se llegó a la conclusión de que estos 2 métodos detectan diferentes tipos de anticuerpos antiinsulina