Detección de mutaciones del gen de HNF1B en niños con malformaciones congénitas renales y del tracto urinario / Detection of mutations of the HNF1B gene in children with congenital anomalies of the kidney and urinary tract

Resumen: Introducción: Las anomalías congénitas del riñón y del tracto urinario se originan de alteraciones genéticas, en su mayoría desconocidas. Las mutaciones en el gen que codifica para el factor hepatocitario nuclear 1B (HNF1B), son la causa monogénica más frecuentemente descrita. Se desconocen datos en Chile y Latinoamérica. Objetivo: Determinar la presencia de variantes del gen HNF1B en niños chilenos con anomalías congénitas del riñón y/o tracto urinario y sus características clínicas. Pacientes y Mé todo: Estudio descriptivo con pacientes entre 10 meses y 17 años, consultantes en Unidad de Nefrología Hospital Luis Calvo Mackenna, período abril - diciembre 2016, portadores de displasia renal quística, displasia/hipoplasia renal no quística y/o riñón en herradura. Se determinaron variantes de HNF1B mediante secuenciación de exones 1, 2, 3 y 4; previa extracción y amplificación de DNA. Se utilizaron enzimas de restricción para definir si variantes eran homo o heterocigotas. Familiares di rectos de casos índices se estudiaron con secuenciación del exón afectado. Resultados: Se incluyeron 32 pacientes, 43,75% varones, mediana edad 11 años. El 65,6% displasia/hipoplasia renal no quística, 31,25% displasia renal quística y 3,15% riñón en herradura. En 2 pacientes (6,25%) se detectó una misma variante genética heterocigota en exón 4, posición 1027 (C1027T), no descrita anteriormente. El estudio de familiares determinó la variante en 3 de 5 individuos, todos sin anomalías nefrouro- lógicas congénitas. Conclusiones: Confirmamos la presencia de una variante genética heterocigota del gen HNF1B, no descrita previamente, dando inicio a la búsqueda de este tipo de mutaciones en nuestro medio, lo cual nos permite aproximarnos al conocimiento de causalidad, determinación de compromiso extrarrenal y consejo genético.

Abstract Introduction: Congenital anomalies of the kidney and urinary tract are caused by genetic alterations mostly unknown. Mutations in the gene that codes for hepatocyte nuclear factor 1B (HNF1B) are the most frequently described monogenic causes. Data are unknown in Chile and Latin America. Objective: To determine the presence of variants of the HNF1B gene in Chilean children with conge nital anomalies of the kidney and/or the urinary tract and their clinical characteristics. Patients and Method: Descriptive study with children aged 10 months to 17 years, patients of the Calvo Mackenna Hospital Nephrology Unit, with cystic renal dysplasia, non cystic renal dysplasia/hypoplasia, horses hoe kidney between April and December 2016. HNF1B variants were determined by sequencing of exons 1, 2, 3 and 4 after DNA extraction and amplification. Restriction enzymes were used to define if the variants were homo or heterozygous. Direct family members of index cases were studied with sequencing of the affected exon. Results: 32 patients were included, 43.75% males, median age 11 years. 65.6% of them had non-cystic renal dysplasia, 31.25% cystic renal dysplasia, and 3.15% hor seshoe kidney. In two patients (6.25%) the same heterozygous genetic variant was detected in exon 4, position 1027 (C1027T), not previously described. The study of relatives found the same variant in three out of five individuals, all without congenital nephro-urological anomalies. Conclusions: We confirmed the presence of a not previously described heterozygous genetic variant of the HNF1B gene. This work initiates the search for this type of mutations in our region which allows us to ap proach the knowledge of causality, determination of extrarenal involvement, and genetic counseling.

[Detection of mutations of the HNF1B gene in children with congenital anomalies of the kidney and urinary tract]. / Detección de mutaciones del gen de HNF1B en niños con malformaciones congénitas renales y del tracto urinario.

INTRODUCTION: Congenital anomalies of the kidney and urinary tract are caused by genetic alterations mostly unknown. Mutations in the gene that codes for hepatocyte nuclear factor 1B (HNF1B) are the most frequently described monogenic causes. Data are unknown in Chile and Latin America. OBJECTIVE: To determine the presence of variants of the HNF1B gene in Chilean children with conge nital anomalies of the kidney and/or the urinary tract and their clinical characteristics. PATIENTS AND METHOD: Descriptive study with children aged 10 months to 17 years, patients of the Calvo Mackenna Hospital Nephrology Unit, with cystic renal dysplasia, non cystic renal dysplasia/hypoplasia, horses hoe kidney between April and December 2016. HNF1B variants were determined by sequencing of exons 1, 2, 3 and 4 after DNA extraction and amplification. Restriction enzymes were used to define if the variants were homo or heterozygous. Direct family members of index cases were studied with sequencing of the affected exon. RESULTS: 32 patients were included, 43.75% males, median age 11 years. 65.6% of them had non-cystic renal dysplasia, 31.25% cystic renal dysplasia, and 3.15% hor seshoe kidney. In two patients (6.25%) the same heterozygous genetic variant was detected in exon 4, position 1027 (C1027T), not previously described. The study of relatives found the same variant in three out of five individuals, all without congenital nephro-urological anomalies. CONCLUSIONS: We confirmed the presence of a not previously described heterozygous genetic variant of the HNF1B gene. This work initiates the search for this type of mutations in our region which allows us to ap proach the knowledge of causality, determination of extrarenal involvement, and genetic counseling.

Dolor y medicina complementaria y acupuntura / Pain and complementary medicine and acupuncture

El objetivo de este artículo es entregar información documentada sobre la situación actual de la Medicina Complementaria y la Acupuntura en Chile, su definición, reglamentación, mecanismos de acción y evidencia. Busca orientar sobre el uso de estas herramientas terapéuticas que son cada vez más solicitadas en el país.

Abnormal osteogenesis in osteoporotic patients is reflected by altered mesenchymal stem cells dynamics.

Bone marrow contains a population of mesenchymal stem cells with the ability to differentiate into cells that form bone, cartilage, adipose, and other connective tissues. Stem cells can be isolated from bone marrow aspirates and expanded in vitro. Presently, most stem cells studies have been performed in cells obtained from "healthy" control subjects. The goal of this study was to compare the functional characteristics of mesenchymal stem cells derived from "healthy" control and osteoporotic postmenopausal women to better understand the mechanisms involved in the pathogenesis of this disease. Osteoporotic and control stem cells have similar morphology and size and express similar cell surface antigens as evidenced by their reactivity with cell specific monoclonal antibodies. Mesenchymal stem cells from osteoporotic women differ from controls in having a lower growth rate than control cells, being refractory to the mitogenic effect of IGF-1, and exhibiting a deficient ability to differentiate into the osteogenic linage as evidenced by the alkaline phosphatase activity and calcium phosphate deposition. We conclude that in osteoporosis stem cell growth, proliferative response and osteogenic differentiation are significantly affected. Also, the study of mesenchymal stem cells from osteoporotic postmenopausal women may provide a better understanding of the mechanisms involved in the pathogenesis of the osteoporosis. It may also serve to test in vitro in rapid manner novel new therapeutic strategies.

[Nutritional status and energy expenditure in elders of differing socioeconomic level]. / Estado nutritivo y gasto energético en ancianos de distinto nivel socioeconómico.

BACKGROUND: Income and socioeconomic status can influence nutritional status of individuals. Since elders are a more vulnerable group to nutritional deficiencies, socioeconomic status could have a special relevance on nutrition of elderly people. AIM: To assess the influence of socioeconomic status on the nutritional status of elders. MATERIAL AND METHODS: Elders of both sexes of high socioeconomic level and age and sex matched elders of low socioeconomic status were studied. Anthropometry, body composition using double beam X ray absorptiometry, resting energy expenditure using an open circuit indirect calorimeter, routine biochemistry, blood levels of folic acid, vitamin B12 and homocysteine were measured in all subjects. RESULTS: Fourteen female elders of high socioeconomic level, 14 females of low level and 12 males of each level were studied. Mean age of females and males was 71.5 +/- 3.7 and 73.9 +/- 4.2 years old respectively. Males and females of high socioeconomic status were taller than their counterparts of low status. Females of high socioeconomic status had a lower body mass index than their pairs of low status (26.3 +/- 3.8 and 30.2 +/- 5.6 kg/m2 respectively p < 0.02). Men of high economic status had a higher fat mass than their pairs of low level (20.3 +/- 3.5 and 15.1 +/- 5.5 kg respectively, p < 0.005). No differences in resting energy expenditure in women of differing socioeconomic level were observed. Men of high level had a higher energy expenditure that their counterparts of low level (36.0 +/- 4.9 and 32.8 +/- 2.2 Kcal/kg lean body mass/day respectively, p < 0.02). Low level male elders had higher serum total cholesterol and triglycerides. Folic acid, vitamin B12 and homocysteine levels were within normal limits. Dietary intake showed deficiencies in calorie, protein and vitamin intake in all subjects. CONCLUSIONS: In this group of elders, low socioeconomic level did not produce a significant impact on nutritional status.

[Quality control of bone densitometry: precision, reproducibility, and clinical application]. / Control de calidad de la densitometría ósea: precisión, reproducibilidad y aplicación clínica.

Dual energy x-ray absorptiometry (DEXA) is one of the most widely used methods for bone mineral density (BMD), total body mass (TBM), total body fat (TBF), percentage of total body fat (%TBF) and total body fat-free mass (TBFFM) measurements. We investigated the in vitro and in vivo accuracy and precision of DEXA in repeated measurements of a lumbar spine phantom and in 30 healthy volunteers. Based on precision, the minimal significant variability (MSV) at 95% confidence level between 2 measurements of the same object or subject was calculated. In vitro accuracy and MSV were 99.8 and 0.9% respectively. In vivo indexes were 99.4 and 0.9% for whole-body BMD, 98.6 and 2% for lumbar spine BMD, 96.6 and 4.8% for femoral neck BMD, 98 and 2.8% for major trochanter BMD, 96 and 5.7% for Ward's triangle BMD, 99.5 and 0.7% for TBM, 98 and 2.9% for TBF, 97.9 and 3% for %TBF and 99 and 1.4% for TBFFM. Our findings indicate that DEXA is a very reliable instrument and in order to be 95% confident of a real change between 2 scans a difference of at least the calculated MSV must be measured.

[Comparative analysis of body composition assessment methods in healthy adult men]. / Análisis comparativo de métodos de evaluación de la composición corporal en varones adultos sanos.

BACKGROUND: The degree of agreement between different methods to assess total body composition is not well known. AIM: To determine the level of agreement for total body fat mass measurement by dual-photon absorptiometry (DEXA), bioelectrical impedance (BIA) and anthropometry using the deuterium dilution method as the gold-standard technique, in normal male volunteers. SUBJECTS AND METHODS: Total body fat mass was measured by DEXA, BIA, anthropometry and deuterium dilution in thirty one healthy men, aged 41.9 +/- 8.6 years old. RESULTS: Mean differences in percentage of total body fat compared with deuterium dilution were 0.3% +/- 2.2, 1.3% +/- 3.4 and 1.8 +/- 2.3% for DEXA1 BIA and anthropometry respectively. DEXA had the lower difference with deuterium dilution and the confidence intervals for this difference (+/- DS) showed that, at the individual level, the maximum difference was 4.4%. CONCLUSIONS: All the methods evaluated gave similar average measurements for total body fat mass, but with different individual variability. In this group of healthy male subjects, DEXA was the best method in terms of agreement with the gold-standard.

[Hip fracture: a case-control study in the metropolitan region I]. / Fractura de la cadera: estudio de casos y controles en la región metropolitana I.

BACKGROUND: Hip fracture is a preventable cause of disability among elderly people AIM: To study factors associated to hip fractures in Chile. PATIENTS AND METHODS: Patients admitted to seven public hospitals in Chile, with hip fracture not due to major accidents, were considered as cases. To each, at least one age and sex matched hospitalized control, without or neoplastic diseases, was assigned. All patients were subjected to an inquiry, using an instrument devised by the WHO. RESULTS: Two hundred sixty eight cases and 501 controls were studied. Cases and controls has similar educational and labor histories. The right hip was fractures in 47% of cases and the left in the rest. Compared with controls, cases had a higher body mass index, loss of height during life, rate of hysterectomy, incidence of smoking and a lower consumption of diary products. Cases had higher risk of falls inside their homes and controls outside. CONCLUSIONS: The obtained information may contribute to the development of preventive measures and reduce the public health impact of hip fracture.

[Diffuse hyperthyroid goiter treated with I131, papillary carcinoma occurring after iodine radioisotope treatment, and thyroxine malabsorption. A clinical case]. / Bocio difuso hipertiroídeo, tratado con I131, cancer papilar de aparición post radioyodo y malabsorción de tiroxina. Caso clínico.

A 50 year-old male with diffuse hyperthyroid goiter treated with I131 who develops a papillary carcinoma is presented. After thyroid resection, substitution therapy with thyroid hormone (levothyroxine) was started, and a selective malabsorption for this hormone was verified.

Effects of progesterone on postovariectomy bone loss in aged rats.

The effects of progesterone on oophorectomy-induced bone loss in aged rats were evaluated. Female rats aged 12 months were divided into three groups: (1) sham-operated controls (SHAM); (2) oophorectomized (OVX); (3) OVX rats treated with progesterone (OVX + PROG). After 20 weeks the dry weight, bone ash, and calcium content of femur, tibia, and fourth lumbar vertebra were significantly lower in OVX than in sham rats. These reductions did not occur in OVX rats treated with PROG. There was no difference in the bone composition between the control and progesterone-treated rats. Vertebral bone histomorphometry showed increased bone resorption as well as increased bone formation parameters in OVX rats. Progesterone treatment inhibited the increased resorption indices, but the bone formation remained elevated. The results indicate that progesterone therapy prevents the postovariectomy bone loss in aged rats. The protective effect of progesterone is mediated by inhibition of bone resorption while maintaining the increased bone formation. These findings suggest that progesterone alone may be a valuable agent for management of postmenopausal osteoporosis.

Hypocalcemia in cancer.

Hypocalcemia based on total calcium measurement is frequent in certain cancers (especially prostate) in association with osteosclerotic bone metastases. In a majority of these patients hypocalcemia is related to the low serum albumin and/or renal failure. True ionized hypocalcemia may be seen as a toxic effect of certain chemotherapeutic agents or as a consequence of hyperphosphatemia due to rapid tumor lysis. In addition, tumors may produce osteoblast-stimulating factor(s) which cause massive accretion of calcium by the skeleton. Isolation and purification of these factors may provide us with unique osteoblast-stimulating factors which may have therapeutic applications.

[Autoimmune polyglandular syndrome. Clinical experience in 21 cases]. / Síndrome poliglandular autoinmune. Experiencia clínica en 21 casos.

The autoimmune polyglandular syndrome is characterized by the association of 2 or more endocrine disorders of autoimmune origin which may coexist with autoimmune disorders in other organs. Roughly 25% of patients with an autoimmune endocrinopathy show evidence of autoimmune disease elsewhere. We report 21 patients with autoimmune polyglandular syndrome classified according to Neufeld.