Correlación genotipo fenotipo de un grupo de pacientes con fibrosis quística / Correlation between phenotype and genotype in a group of patients with cystic fibrosis

Background: Cystic fibrosis (CF) is the most common lethal autosomic disease in Caucasians, with a global incidence of 1:3000 newborns. More than 900 mutations have been described, involving the Cystic Fibrosis Transmembrane Regulator (CFTR). The ÆF508 mutation is present in 60 percent of alleles studied worldwide. Aim: To report 25 patients with cystic fibrosis in whom a genetic study was done. Material and methods: Twenty five patients (14 men, aged between 18 months and 25 years) with a diagnosis of cystic fibrosis based on clinical features plus two abnormal sweat tests are reported. The genetic study considered the 20 most common mutations in cystic fibrosis and was done in genomic DNA of peripheral lymphocytes, by polymerase chain reaction. Results: A mutation was found in 75 percent of analyzed alleles. ÆF508 was present in 50 percent of cases (ÆF508/ÆF508 in 8 and ÆF508/other in 11). When ÆF508 was present, pancreatic insufficiency was always a feature and nutritional status was worse. Respiratory involvement was variable, both for homozygous and heterozygous cases. Other severe mutations such as W1282X and G542X were related to clinical manifestations similar to those found in ÆF508 mutation. Diagnosis was made before six months of age in 12 patients. The clinical presentation was meconium ileus and there was a family history of the disease in most cases. The majority of cases of early diagnosis presented severe mutations, but milder respiratory symptoms and lesser nutritional compromise at the time of assessment. Conclusions: Most patients studied had a severe cystic fibrosis mutation, which was associated with more severe respiratory, pancreatic and nutritional involvement. The early diagnosis of the disease, which would allow to improve the prognosis and the quality of life, must be emphasized

Anticuerpos anti-tiroglobulina en el seguimiento de pacientes con cáncer diferenciado de tiroides: ¿marcadores de enfermedad residual o recidivante? / Anti thyroglobulin antibodies in the follow up of patients with differentiated thyroid cancer

Background: Anti thyroglobulin antibodies are present in 25 percent of patients treated for a differentiated thyroid cancer, invalidating thyroglobulin determination. Those patients subjected to total thyroidectomy and free of disease, should reduce the production of these antibodies, due to the lack of antigenic stimulus. Therefore, anti thyroglobulin antibodies could be useful to detect early relapses. Aim: To assess the relationship between anti thyroglobulin antibodies and the evolution of the disease in patients treated for thyroid cancer. Material and methods: Retrospective analysis of 26 patients treated for thyroid cancer with positive anti thyroglobulin antibodies, followed for three years. These were divided in those with or without lymphocytic thyroiditis (19 and 7 respectively). Results: At the first year of follow up, anti thyroglobulin antibody concentration was 401ñ94.9 UI/ml (xñsem) in patients with thyroiditis and 38.9ñ8.9 UI/ml in those without thyroiditis (p < 0.005). During the three years of follow up, no differences in anti thyroglobulin antibodies were observed between patients with or without tumor relapse. Conclusions: Concentration of anti thyroglobulin antibodies was higher in patients with thyroiditis and did not differentiate patients with tumor relapse

Alta prevalencia de enfermedad tiroidea subclínica en sujetos que concurren a control de salud / High prevalence of subclinical thyroidal disease among individuals attended in occupational health examinations

Background: There is no information about the prevalence of thyroidal diseases in the general Chilean population. Aim: To assess the prevalence of thyroidal diseases in individuals attended in occupational health examinations. Subjects and methods : Four hundred seventy two individuals were examined between 1998 and 1999. In all, serum levels of thyroid hormones, TSH and anti thyroidal antibodies (anti microsomal, anti thyroid peroxidase and anti thyroglobulin) were measured. Results: Forty four subjects were excluded from the study due to an incomplete medical record and 18 due to a personal history of thyroidal disease. Abnormal serum levels of thyroid hormones or TSH were detected in 28 subjects (6.8 percent). Four (1 percent) had hypothyroidism, 23 a subclinical hypothyroidism (5.6 percent) and one (0.2 percent) had hyperthyroidism. In 87 subjects (21.2 percent) at least one of the antibodies was positive. Positive anti thyroid antibodies were found in 14 of 28 subjects (50 percent) with abnormal thyroid hormone levels, compared with 73 of 382 subjects (19.1 percent) with normal thyroid hormone levels. Thyroid dysfunction was twice as frequent in women than in men. Conclusions: In this sample, a 6.8 percent prevalence of abnormal thyroid function tests was detected

Monitoreo de ciclosporina en pacientes con diltiazem / Cyclosporine monitoring en patients with diltiazem

Diltiazem (DLTZ) es un inhibidor de la metabolización de la ciclosporina (C y A) y se usa en el paciente transplantado para disminuir las dosis de C y A. Sin embargo, por el mecanismo de acción de DLTZ esta estrategia se asocia a una mayor proporción de metabolitos de C y A circulantes. Existen en el país dos técnicas para determinar la concentración C y A en sangre: 1) TDX automatizado que mide el compuesto base y hasta un 20 por ciento de metabolitos y 2) RIA específico es una técnica que determina hasta un 5 por ciento de metabolitos y tiene una variabilidad muy cercana al HPLC (gold standard). El objetivo de este estudio fue determinar el comportamiento de estas dos técnicas al introducir DLTZ en pacientes transplantados renales. Diez pacientes sometidos a transplanes renal, con buena función del injerto y con inmunosupresión con C y A Neoral fueron incorporados a un protocolo de DLTZ en dosis 120 a 180 mg/día. La serie estuvo constituida por cinco hombres y cinco mujeres con edad promedio de 33,8 ñ 11,3 años (rango 15-49). Antes y después del inicio de DLTZ se midieron niveles de C y A. Con estos valores se calculó el área total bajo la curva y se estimó utilizando dos fórmulas abreviadas conocidas. Las dosis de C y A antes y después de DLTZ fue 4,9 ñ 1,4 y 3,5 ñ 1,1 mg/kg/día respectivamente (p<0,001). Después de DLTZ los valores de AUC total y abreviadas fueron mayores con TDX en aproximadamente un 20 por ciento (p=0,01). Al comparar las AUC abreviadas TDX con AUC total RIA después de DLTZ los valores también fueron mayores. Esta comparación con RIA no mostró diferencias. Los cálculos realizados con TDX en presencia de DLTZ fueron mayores que con RIA, lo que puede estar relacionado a la diferente proporción de metabolitos que cada técnica es capaz de medir. Estas diferencias deben considerarse especialmente cuando se estima la AUC total con fórmulas abreviadas ya que puede afectar directamente el manejo clínico de estos pacientes

Medición de 17-OH progesterona sanguínea en recién nacidos chilenos: antecedentes para implementar un programa de detección neonatal de hiperplasia suprarrenal congénita / 17 OH progesterone measurement in blood of chilean newborns: as a background to start a congenital adrenal hyperplasia screening program

Background: The early diagnosis and therapy of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can prevent adrenal crises and erroneous gender assignment in affected newborns. To achieve this goal neonatal mass-screening programs have been developed, measuring blood 17 alpha-hydroxyprogesterone (17OHP). In Chile there is no experience with this type of screening. Aim: To develop a method for measuring 17OHP in filter paper blood specimens. To obtain reference ranges and determine neonatal 17OHP threshold levels according to gestational age and birth weight. To analyze factors affecting the cost-efficiency ratio and suggest recommendations for the organization of a neonatal screening program for CAH in Chile. Material and methods: Nine hundred twenty two newborns were studied. 17OHP was measured using double antibody radioimmunoassay in filter paper blood samples obtained 48 h after birth. Reference ranges were determined according to gestational age and birth weight and a cutoff point of 25 ng/ml was established. Results: Seventeen newborns had 17OHP over the cutoff value. They were assessed by a pediatric endocrinologist and in none of them, CAH was confirmed. Therefore the false positive rate of the determination was 1.8 percent. Among these newborns with elevated 17OHP, 66 percent had a birth weight below 1.5 kg and 5.8 percent, a birth weight between 1.5 and 2.5 kg. The cost per reported result was US $ l. Timing of the recall was between the 3 and 10 days of life. No newborn missed the follow-up. Discussion: To increase the cost-efficiency ratio of an eventual neonatal screening program, newborns with birth weights below 1.5 kg should be excluded and cutoff points should be defined according to birth weight

Exceso de mineralocorticoides en hipertensos esenciales: enfoque clínico diagnóstico / Evidences for mineralocorticoid excess in essential hypertension: clinic and diagnosis viewpoint

Background: Primary hyperaldosteronism is more frequent among subjects with essential hypertension than previously thought. The prevalence, according to local and international evidence could fluctuate between 9 and 10 percent. Aim: To investigate if subjects with essential hypertension have different aldosterone and renin plasma levels than normotensive subjects. Patients and methods: One hundred twenty five subjects with essential hypertension, not receiving medications for at least two weeks prior to the study and 168 age and sex matched normotensive controls were studied. Blood was drawn between 9 and 10 AM during a sodium free diet to determine plasma aldosterone, plasma renin activity and potassium. Results: Plasma aldosterone was higher in hypertensive subjects than controls (11.6 ñ 7.6 and 9.9 ñ 5.1 ng/dl respectively; p=0.04). Plasma renin activity was lower in hypertensives than controls (1.42 ñ 1.28 and 1.88 ñ 1.39 ng/ml/h respectively; p<0.001). Thus, plasma aldosterone/plasma renin activity ratio was higher in hypertensives (13.8 ñ 13.5 and 8.3 ñ 7.8; p<0.001). A pathological ratio was defined as over 25, corresponding to the mean plus two standard deviations of the control group. Primary hyperaldosteronism was found in 5/125 hypertensives (4 percent) and 1/168 normotensive subject (0.6 percent). None had hypokalemia. Conclusions: Subjects with essential hypertension have higher plasma aldosterone and lower plasma renin activity than normal controls. A plasma aldosterone/plasma renin activity over 25 was defined as abnormal

Alta prevalencia de hiperaldosteronismo primario no diagnosticado en hipertensos catalogados como esenciales / High prevalence of undiagnosed primary hyperaldosteronism among patients with essential hypertension

Background: Classically, primary hyperaldosteronism was diagnosed in no more than 1 percent of patients with hypertension, when hypokalemia was used as the screening test. However, numerous patients with primary hyperaldosteronism do not have hypokalemia and the disease remains undiagnosed. Aim: To assess the prevalence of normokalemic primary hyperaldosteronism among patients classified as having essential hypertension. Patients and methods: One hundred hypertensive patients with a blood pressure over 145/95 were studied. Plasma aldosterone and plasma renin activity were measured in all. A primary hyperaldosteronism was diagnosed when high aldosterone levels (over 16 ng/dl) and low plasma renin activity (below 0.5 ng/ml/h) coexisted in two blood tests or the aldosterone/plasma renin activity ratio was over 50. A probable primary hyperaldosteronism was diagnosed when the ratio was between 25 and 50 and these patients were subjected to a Fludrocortisone test to confirm the diagnosis. A dexametasone suppression test was done to discard glucocorticoid remediable aldosteronism. An adrenal TAC scan was done to all patients with primary hyperaldosteronism. Results: A diagnosis of primary hyperaldosteronism was reached in ten patients. Seven had elevated aldosterone and low plasma renin activity. In three the diagnosis was confirmed with the fludrocortisone test. All ten patients had normal serum potassium levels. Dexametasone suppression test was positive in three patients, that normalized their blood pressure levels. Adrenal TAC scans showed an adenoma in one patient and hyperplasia in another. Conclusions: Primary hyperaldosteronism is more frequent than previously thought, it is overlooked when hypokalemia is used as the screening test and it can only be diagnosed measuring plasma aldosterone and renin activity

Autoanticuerpos anti-tiroglobulina: detección y posible interferencia en la medición de tiroglobulina en suero / Thyroglobulin autoantibodies: detection and possible interference in serum thyroglobulin measurement

Background: Thyroglobulin measurement is useful for the follow up of patients subjected to total thyroidectomy for differentiated thyroid carcinoma. Thyroglobulin autoantibodies may interfere with its determination. Aim: To measure thyroglobulin autoantibodies and their interference with thyroglobulin determination. Material and methods: The presence of thyroglobulin autoantibodies was investigated in 801 serum samples sent to the laboratory for measurement of thyroglobulin levels. A serum was considered positive for these autoantibodies when radioactivity corresponding to 125I-thyroglobulin bound to thyroglobulin autoantibodies, precipitated with human gamma globulin, exceeded in 1.4 times that of a negative sera pool. In positive sera, thyroglobulin autoantibody concentration was measured and its interference with thyroglobulin radioimmunoassay was assessed through a recuperation test using exogenous thyroglobulin. Results: Thyroglobulin autoantibodies were detected in 149 sera (18.6 percent). Of these, 65 had a recuperation that fluctuated between 1 and 80 percent. Thyroglobulin autoantibody concentration was negatively correlated with recuperation percentages (r= -0.64; p <0.001) but not with thyroglobulin concentrations (r= 0.08). Thyroglobulin was higher in positive sera with a recuperation over 80 percent than in sera with a recuperation of less than 80 percent (12.7 ñ 1.7 and 5.9 ñ 0.6 ng/ml, respectively; p <0.001). Conclusions: Thyroglobulin autoantibodies interfere with thyroglobulin measurement by radioimmunoassay, sequestering variable amounts of thyroglobulin. The presence of these autoantibodies must be investigated prior to thyroglobulin determination

Capacidad de predecir una recaída de lupus eritematoso generalizado, mediante anticuerpos anti-DNA de hebra doble, por la técnica de Farr / Predictive capacity of double stranded anti DNA antibodies for relapses in patients with inactive systemic lupus erythematosus using Farr technique

Background: Patients with inactive systemic lupus erythematosus (SLE) and elevated high affinity double-stranded anti-DNA antibodies (anti-dsDNA), measured using Farr technique, would have a risk of relapse that fluctuates between 40 to 80 percent according to different series. Aim: To study the association between anti-dsDNA levels measured using Farr technique and disease activity and their predictive capacity for relapses. Material and methods: Anti-dsDNA antibodies were measured according to Farr method in 60 healthy subjects, 69 patients with other connective tissue diseases and in 120 patients with SLE. Farr positive were considered those individuals with anti-dsDNA levels over 10.4 IU/ml. Disease activity, assessed using MEX-SLEDAI score was related with anti-dsDNA levels in 101 patients. Forty seven patients with inactive disease were followed for 17ñ14 months. Results: Anti-dsDNA levels were 3ñ2.5 IU/ml (range 1-26) in subjects without LED, and 127ñ500 IU/ml (range 1-5280) in patients with LED. Sixty subjects had an active SLE and 43 (72 percent) were Farr positive; in 41 the disease was inactive and 13 (32 percent) were Farr positive (p <0.001), OR 5.45. Twelve of the 47 followed patients had a relapse and 10 (83 percent) were Farr positive. Of those that did not have a relapse, 13 (37 percent) were Farr positive (p< 0.02, RR 5.22). Six of 15 patients that were followed for more than on year (40 percent), were Farr positive. Conclusions: Elevated anti-dsDNA antibodies measured using Farr technique in patients with inactive generalised lupus erythematosus, predicted the risk of relapse. However less than half of patients with inactive disease and elevated Farr relapsed in a period of one year. The need to treat patients with inactive SLE and positive Farr should therefore be considered debatable

Medición de la actividad de renina plasmática a niveles bajos: optimización del método / Measurement of low levels of plasma renin activity: a methodological improvement

Background: The present method to measure plasma renin activity is cumbersome and imprecise, factors that limit its clinical application. Aim: To assess the importance of blood sampling conditions and the usefulness of increasing incubation time to measure plasma renin activity at low levels. Patients and methods: Twenty hypertensive patients, 14 female, aged 14 to 76 years old, were studied. Two blood samples were obtained after a 10 min rest in the sitting position and after a 30 min rest in supine position. One blood sample, of each condition was sent lo the laboratory at room temperature and the other sample was sent refrigerated. Angiotensin I concentration was determined after 3 h of enzymatic incubation at 37°C and, in subjects with an activity of less than 1 ng/ml/h, after 18 h of incubation. Results: No significant differences in plasma renin activity were observed between the samples obtained with different rest times or different transportation methods. In people with low plasma renin activity, the 18 h enzymatic incubation reduced the lower detection from 0.3 to 0.014 ng/ml/h and the coefficient of variation from 14.4 to 3.2 percent. Conclusions: A simplified blood sampling method does not change plasma renin activity values, and tbe longer enzymatic incubation in people with low plasma renin activity improves both the sensitivitv and accuracy of the determination

Diagnóstico molecular de hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa, variedad perdedora de sal, en población chilena / Molecular diagnosis of salt wasting congenital adrenal hyperplasia, caused by deficit of 21-hydroxylase, in the Chilean population

Twenty five patients with salt wasting congenital adrenal hyperplasia, that had 17-hydroxyprogesterone levels above 30 ng/ml, were studied. In all patients, a polymerase chain reaction (PCR) with selective primers was done with extracted genomic DNA, to amplify the active gene and specific primers for normal or mutated alleles of 50 chromosomes of the 25 patients. The higher frequency affected the ASIn2 in 26 percent of cases, followed by mutations Arg357Trp in 22 percent of cases and Gln319Stop in 12 percent and deletion in 12 percent. The frequent genotypes were homozygosity for ASIn2 (16 percent), homozygosity for Arg357Trp (12 percent) and the homozygote deletion of the gene in 12 percent. The most frequent mechanisms of genetic deficiency of 21-hydroxylase were the mutations ASIn2 Arg357Trp. This type of studies allows prenatal diagnosis and genetics counseling

Efecto de dos formas de suplementación de vitamina D en el crecimiento y metabolismo óseo del lactante / Effects of 2 ways of vitamin D supplementation on infant growth and bone metabolism

Se evaluó el efecto sobre el metabolismo óseo y crecimiento del lactante menor de suplementos de vitamina D de 600.000 UI en el primero y sexto mes (norma ministerial) ante una dosis diaria de 400 UI hasta el sexto mes, en dos grupos de lactantes normales. En controles mensuales se midieron peso, talla, circunferencia craneana, presión arterial, calcemia, fosfemia, fosfatasas alcalinas, hormona paratiroidea y 1.25 (OH)2 vit D. Se encontraron diferencias estadísticamente significativas en favor de los niños que recibían 400 UI diariamente, a contar del tercer mes en la talla, del sexto mes en el peso y del octavo mes en la circunsferencia craneana. La presión arterial fue más alta en los pacientes que recibieron megadosis semestrales de la vitamina, especialmente 30, 60, 90 y 120 días, después de la primera de ellas. La concentración plasmática media de 1,25 (OH)2 vit D fue más alta en los casos tratados con megadosis (110 y 96 pg/ml en el primero y el sexto mes respectivamente), que en los que recibía dosis diarias (55 pg/ml en el primero y sexto mes). No se encontraron diferencias en las restantes variables sanguíneas analizadas. La administración de 400 UI diarias es más fisiológica, promueve mayor crecimiento, evita riesgos de intoxicación a corto plazo y potencial a largo plazo por la hipertensión inducida a esta edad. La norma ministerial debiera ser revisada

Neoral de novo: experiencia preliminar en transplante renal / Novo neoral: preliminary experience in renal transplantation

Se realizó un estudio retrospectivo comparativo entre 2 grupos de enfermos sometidos a un transplante renal en el Hospital Clínico de la Universidad Católica. El estudio incluye la serie de los últimos 12 enfermos que recibieron terapia inmunosupresora con Ciclosporina nueva formulación (Neoral R) y un grupo de control constituido por 11 enfermos con Sandimmun, comparables en histocompatibilidad, isquemia y características generales. El objetivo es estudiar el tiempo que demoran ambas formulaciones de Ciclosporina en alcanzar el rango terapéutico óptimo, la dosis necesaria para alcanzar estos niveles, la repercusión en relación a la función renal y la frecuencia de rechazo. En ambos grupos no hubo diferencias significativas en la fecha de inicio de la Ciclosporina, sin embargo el rango terapéutico óptimo en el grupo que usó Neoral, se alcanzó el día 14 y en el grupo con Sandimmun éste se logró en el día 25 (p = 0,025). La dosis necesaria para alcanzar este rango terapéutico fue similar en ambos grupos (6,2 y 6,8 mg/Kg) (NS). El haber alcanzado una dosis terapéutica en forma más rápida, no afectó la función renal, ya que ambos grupos tuvieron curvas de creatinina similares. La frecuencia de rechazo fue mayor en el grupo tratado con Sandimmun (45 por ciento), en relación a un 9 por ciento del grupo de Neoral (p = 0.042)

Efecto de un preparado en forma de gel de 17 ß estradiol sobre diferentes parámetros hormonales en mujeres menopáusicas / Effects of a 17 ß estradiol gel preparation on different hormonal parameters in menopausal women

Different delivery forms of supplemental estrogens may differ in their hormonal effects. The aim of this study was to assess the effects of a daily dose of 2.5 g of 17 ß estradiol transdermal gel, given during four weeks, on hormon levels of six postmenopausal women. At the fourth week we observed a significant increase in estradiol and a dicrease in FSH levels. estrone levels alsa increased but the estradiol-estrone ratio was maintained in values over 1. No changes in SHBG or IGF1 levels were observed. Two patients that used the gel in the abdominal skin achieved lower estradiol levels (below 60 pg/ml). We conclude that the gel increased serum estradiol levels over 60 pg/ml in four of six women, that there is a big individual variability and the application zone could influence the serum estradiol levels achieved

Respuesta cardiovascular al ejercicio a gran altura en trabajadores crónicamente expuestos a hipoxia hipobárica intermitente / Cardiovascular response to exercise at high altitude in chronically exposured workers to intermittent hypobaric hypoxia

The isottonic work perfomance was assessed in 34 workers aged 35 ñ 5.8 years old that had working of four days at 4500 m over the sea level and resting periods of other four days at the sea level during at least two years. Subjects were assessed in one occasion at the sea level, and at the first and fourth day of the working shift at 4500 m over the sea level. resting arterial oxygen saturation in theses three periods was 97 ñ 1.1, 88 ñ 18 and 91 ñ 1.1 percent respectively (p<0.01) and markedly decreased during maximal and submaximal exercise at 4500 m over sea level. Evercise duration in the three periods was 931 ñ 210, 775 ñ 105 and 778 ñ 105 seg respectively (p<0.001). Heart rate in the resting period was at least 10 percent higher and maximal and submaxilmal rates were lower at the high altitude. No differences in blood pressure or packed red cell volume were observed. Exercise duration correlated inversely with age (r=-0.49 p=0.03) and directly with maximal heart rate (r=0.44 p=0.009) at the sea level. No correlation between aerobic capacity and other measured parameters was observed. These results show no differences in the cardiovascular response to exercise between the first and fourth day of stay at high altitude in workers chronically exposed to intermittent hypobaric hypoxia

Una no tan breve historia / A non very short history

La historia de la física atómica y nuclear es una muy lenta incubación intelectual del hombre. Para ejemplificarla y centrarla en nuestra vida habitual, imaginemos que cada hora sean 6 años, y un día serán, entonces, 144 años. El hombre apareció por ahí por el primero de Enero. Durante 11 largos meses se incuba la prehistoria y, así, por el primero de Diciembre, se inicia la Historia Moderna. La historia griega se hace presente por el 8 de Diciembre; el 24 de Diciembre nace Santo Tomás de Aquino; la Física Nuclear Moderna se inicia por ahí a las 10 A.M. del 31 de Diciembre; Hiroshima y Nagasaki restallan en la Historia a las 17 horas y a las 18 horas del mismo día se inicia la Medicina Nuclear