Carotid intima-media thickness as a cardiovascular risk marker in pediatric end-stage renal disease patients on dialysis and in renal transplantation.

Cardiovascular diseases are the principal cause of morbidity and mortality among young adults with chronic renal disease. Atherosclerotic structural changes as detected by high-resolution B-mode ultrasonography preceed clinical findings by several decades. The carotid intima-media thickness (cIMT) is being used as a marker of early atherosclerosis. We determined the cIMT of common carotid artery (CCA) in 8 asymptomatic children on dialysis or 12 after renal transplantation for comparison with 30 healthy controls. This prospective study of 40 children showed a mean age of 13.5 years (range, 8 to 18). We evaluated cIMT, hemoglobin, serum creatinine levels, lipid profile, and homeostasis model assessment (HOMA). The statistical analysis for variables with normal distribution was Student's t test. Parameters with a non-normal distribution were evaluated by the Mann-Whitney or Spearman correlation analysis with P < .05 considered statistically significant. The mean measurements of cIMT (mm) of both CCA were dialysis 0.450 +/- 0.042; transplant 0.467 +/- 0.033, and controls 0.380 +/- 0.009 (P < .03). The homa levels of 2.45 +/- 0.98 for dialysis and 1.8 +/- 0.62 for transplant, were both significantly higher than the control group (0.8 +/- 0.09; P < .01). The Ca x P product was higher in dialysis vs transplant group: 63.0 +/- 10.0 versus 46.2 +/- 2.2 (P < .03). The intact parathyroid hormone levels were 666.7 +/- 276.7 versus 44.2 +/- 2.8, respectively (P < .008). The low-density lipoprotein cholesterol was 129.0 +/- 23.1 versus 80.8 +/- 10.6, respectively (P < .04). The cIMT correlated with the duration of dialysis before transplantation. Changes in IMT can be detected by ultrasonography in early childhood in uremic patients. The etiology of atherosclerosis is multifactorial in children with end-stage renal disease. It seems possible to prevent or improve the factors related to cardiovascular risk in these patients.

Salt-wasting congenital adrenal hyperplasia: detection of mutations in CYP21B gene in a Chilean population.

The steroid 21-hydroxylase deficiency (21OHD) is the most frequent cause of congenital adrenal hyperplasia. We have characterized the disease-causing mutations in the 21-hydroxylase genes of 63 patients with salt-wasting congenital adrenal hyperplasia from a Chilean population of Hispanic origin, a group that has been scarcely evaluated. Using allele-specific PCR, lesions were identified in 97 chromosomes out of 126 tested (77%). The most frequent findings were the gene deletion or large gene conversion (LGC) = 22.9%, I2 splice = 19%, R357W = 12.7%, and Q319X = 10.5%. We did not find alleles with the mutation F308insT and we found three alleles with the cluster E6. The frequency of the point mutation R357W was at least two times more frequent than the one found in Caucasians populations, but similar to that communicated in Asian populations; this finding may be explained by the Asian ancestry of our South-Amerindian population. The frequency of Q319X was also high, similar only to those patients studied in Italy and in a neighboring Argentinian population. In summary, this is a genetic characterization of 21OHD made in an almost pure Hispanic population in Latin America. The high frequency of deletion of CYP21B gene, I2 splice, R357W, and Q319X mutations probably reflects the European-Caucasian-Spanish influence of the conquerors, mixed with Amerindians of Asian ancestry and modulated by other European immigrations.

Y chromosome sequences in Turner's syndrome: association with virilization and gonadoblastoma.

UNLABELLED: The presence of Y chromosome fragments in patients with Turner's syndrome is known to increase the risk of gonadoblastoma and virilization. Y chromosome material is detected in up to 6% of patients with Turner's syndrome by karyotype. By DNA analysis, Y chromosome sequences have been reported in 0-60% of patients. The putative gonadoblastoma gene has been mapped to the pericentromeric region of the Y chromosome increasing the interest in studying these sequences. AIMS: 1. To determine the frequency of occult Y chromosome sequences in patients with Turner's syndrome. 2. To analyze the clinical implications of Y sequences detected by karyotype and occult Y sequences. STUDY DESIGN: Cross-sectional study of 58 patients with Turner's syndrome (30 45,X; two with structural anomalies; 26 mosaic [two of whom were 45,X/46,XY]). SRY, TSPY and DYZ3 sequences were amplified by PCR using genomic DNA from peripheral blood. RESULTS: All three Y chromosome sequences were found in one out of 56 patients whose karyotype was not suggestive of having Y chromosome material and in one patient with 45,X/46,Xr(X) karyotype. The patients with the ring chromosome and 45,X/46,XY karyotype underwent surgery and were found to have a gonadoblastoma and dysgerminoma. The four patients with Y chromosome material had non-virilized female genitalia. CONCLUSIONS: Analysis by PCR was more sensitive in detecting Y chromosome sequences than conventional karyotype. The presence of Y material was not associated with virilization. We confirmed the association of Y fragments and gonadoblastoma at an early age.

[Delayed puberty and hypogonadotrophic hypogonadism: differential diagnosis with prolactin stimulation probe with chlorpromazine]. / Retardo puberal e hipogonadismo hipogonadotrófico: diagnóstico diferencial con la prueba de estimulación de prolactina con clorpromazina.

We studied the changes in plasma levels of prolactin after an intramuscular injection of 0.33 mg/kg chlorpromazine and changes in plasma levels of LH and FSH after the injection of 100 micrograms iv GnRH, in 16 patients with delayed puberty, 10 patients with hypogonadotrophic hypogonadism and 6 healthy controls. Prolactin response was significantly lower in patients with hypogonadotrophic hypogonadism compared to subjects with constitutional delayed and healthy controls (delta Prolactin 7.05 +/- 1.7, 28.9 +/- 2.7 and 22.0 +/- 3.4 ng/ml respectively). LH response to GnRH was also lower in patients with hypogonadotrophic hypogonadism, compared to the other two groups (delta LH 4.3 +/- 2.5, 13.4 +/- 5.4 and 17.2 +/- 4.8 mUI/ml respectively) however, there was a great overlapping of values. No differences between groups were observed in responses of FSH, testosterone and estrogens to GnRH. It is concluded that prolactin response to chlorpromazine is useful in the differential diagnosis of constitutional delayed puberty.

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

BACKGROUND: The most frequent cause of congenital adrenal hyperplasia, manifested as virilization and salt wasting, is the deficit of 21-hydroxylase. This disease is originated by mutations of the gene CYP21 that codifies this enzyme, mostly recombination between this gene and its inactive pseudogene called CYP21P. AIM: To study the molecular origin of this enzyme deficiency in Chilean patients. PATIENTS AND METHODS: 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 (Allele-specific PCR). RESULTS: The affected allele was identified in 39 (78%) of the 50 chromosomes of the 25 patients. The higher frequency affected the ASIn2 in 26% of cases, followed by mutations Arg357Trp in 22% of cases and Gln319Stop in 12% and deletion in 12%. The identification of two affected alleles in a same patient was achieved in 17 cases (68%). The most frequent genotypes were homozygosity for ASIn2 (16%), homozygosity for Arg357Trp (12%) and the homozygote deletion of the gene in 12%. CONCLUSION: The most frequent mechanisms of genetic damage in this population of patients with salt wasting congenital adrenal hyperplasia due to deficiency of 21-hydroxylase were the mutations ASIn2 and Arg357Trp. This type of studies allows prenatal diagnosis and genetic counseling.

Zinc supplementation increases growth velocity of male children and adolescents with short stature.

We assessed the effect of zinc supplementation on growth velocity in 79 children and adolescents (48 males, 38 females) with idiopathic short stature. Their height-for-age was < 5th percentile (NCHS standards) and their weight-for-age was normal. Patients were assigned randomly to a supplemented group (S) to receive Zn 10 mg/day or to a placebo (P) group, according to gender and age, and were followed-up for 12 months using a double-blind design. Weight, height, armspan, length of lower segment and plasma and hair concentrations of Zn were measured at 0, 3, 6 and 12 months. On admission and at 6 months, energy, protein, dietary fiber and zinc intakes were similar for groups S and P; mean zinc intake was < 6.5 mg/day. No differences were found in plasma zinc, hair zinc, weight, armspan or lower segment increments. Pre-adolescent males in group S had a significantly greater increase in stature compared with group P (6.2 +/- 2.1 versus 4.5 +/- 1.2 cm/year p < 0.025); z score improved from -2.42 to -2.24 in group S and from -2.63 to -2.61 in group P. For adolescent males, the difference was also significant (8.3 +/- 1.5 versus 6.2 +/- 2.1 cm/year; p < 0.025). No differences were noted in females. In Chilean male schoolchildren and adolescents with idiopathic short stature, zinc supplementation increases growth velocity over a 12-month period.

Mutations in the CYP21 B gene in a Chilean population with simple virilizing congenital adrenal hyperplasia.

Steroid 21-hydroxylase deficiency (21OHD) compromises about 95% of all cases of congenital adrenal hyperplasia. We have characterized the disease-causing mutations in the steroid 21-hydroxylase genes of 19 Chilean patients (12 females and 7 males) with the simple virilizing (SV) form of 21OHD and compared them with other SV-populations. Using allele-specific polymerase chain reaction, we identified lesions in 28 chromosomes out of 38 tested (73.7%). The most frequent finding was the mutation I173N=12/38 (31.6%) similar as described in Caucasian, Asian and other Hispanic populations, where this mutation represents around 20-40% of the genetic defects in the CYP21B gene. The mutation V282L=4/38 (10.5%) and deletion (Del) or large gene conversion (LGC)=3/38 (7.9%) were also frequently detected. Only 2 alleles carried the mutation I2 splice (5.3%), this frequency is lower than that reported in Caucasian or in Mexican populations. We did not find alleles with the mutations R357W, Cluster E6, P31L and P454S in these patients. The complete genotype was determined in 11/19 patients (58%) and one allele in 6/19 patients (31.6%). In summary, about 30% of the Chilean population with SV 21OHD presented the missense mutation I173N as described in other populations. The frequency of the other lesions showed differences even between populations with similar genetic background.

A novel homozygous nonsense mutations E135* in the type II 3beta-hydroxysteroid dehydrogenase gene in a girl with salt-losing congenital adrenal hyperplasia. Mutations in brief no. 168. Online.

Mutations in the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) type II gene have been reported in a small number of affected females. We report a 46,XX girl born to consanguineous parents from Chile. At birth, she had normal but hyperpigmented female external genitalia. At 60 days she presented salt loss. At 20 months, the diagnosis of classic salt-losing 3beta-HSD deficiency was made based on an elevated serum 17-hydroxpregnenolone concentration and a high 17 hydroxypregnenolone/17-hydroxyprogesterone ratio. Genomic DNA was amplified by PCR and screened for mutations by denaturing gradient gel electrophoresis and directly sequenced. A novel homozygous E135* mutation was found in the 3beta-HSD type II gene of the patient while her parents were heterozygotes. This novel nonsense homozygous E135* mutation led to encode a predicted truncated 134 amino acid protein instead of the native 371 amino acid 3beta-HSD type II protein. This predicted product is consistent with the severe 3beta-HSD deficiency in this girl.

Ensayo clinico con broncodilatadores en bronquitis obstructiva del lactante y preescolar menor. / Clinical trial with bronchodilator agents in obstructive bronchitis of infants and preschool children

Con el objeto de evaluar la respuesta con broncodilatores en ninos menores con bronquitis obstructiva, se realizo un estudio clinico con fenoterol y metaproterenol, comparandolo con un grupo control. El analisis estadistico de cada parametro clinico demostro diferencia significativa solamente en relacion al descenso de la frecuencia respiratoria con el uso de estimulantes beta-adrenergicos con respecto a los controles. En los demas parametros no se demostro diferencia estadisticamente significativa entre el grupo con broncodilatores y el grupo control. Por lo tanto, este estudio corrobora la utilidad limitada del uso de broncodilatores en bronquitis obstructiva, traducida un una disminucion de la frecuencia respiratoria, que indirectamente demuestra una disminucion de la resistencia al flujo aereo, hecho que deberia ser confirmado con pletismografo