Ketoconazole alters cyclosporine pharmacokinetic profile and may predispose to acute rejection.

Ketoconazole (KET) is frequently used as a cyclosporine (CyA)-sparing agent. Adequate exposure to CyA is critical to avoid acute rejection (AR) or chronic rejection (CR). We compared the pharmacokinetic profiles of nine stable renal transplant patients on CyA before and after conversion to KET (200 mg/d of KET simultaneous with CyA). The CyA doses were adjusted to achieve similar drug exposures. The mean dose reduction of CyA while on KET was 83% from 3.2 +/- 0.9 to 0.6 +/- 0.2 (P <.000). Addition of KET produced a significant decrease in the absorption parameters of CyA and an increased elimination half-life. Coefficient of variation (CV) of AUC was significantly increased. Serum creatinine (SCr) at 3 months after switch remained the same. One patient experienced a grade I AR episode (11%). There were no adverse effects related to KET. Although addition of KET to CyA can significantly decrease the CyA dose, the observed pharmacokinetic changes involved decreased absorption and increased CV, which may respectively relate to AR and CR. The 11% AR rate observed is of concern. We do not recommend switching patients to KET as this may imply an increased risk of late AR or CR.

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.

[Identification of mutation in the gene cystic fibrosis transmembrane regulator (CFTR) in Chilean patients with cystic fibrosis]. / Identificación de mutaciones en el gen CFTR en pacientes chilenos con fibrosis quística.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene, that codes for a chloride channel located in the apical surface of epithelial cells. The main role of this protein is the regulation of chloride transport, and secondarily, of sodium and water to the extracellular space. More than 900 gene mutations have been described, and their relative frequency in different populations depends on their ethnic origin. AIM: To report the findings of Chilean patients with cystic fibrosis, in whom the presence of 20 common mutations was analyzed. PATIENTS AND METHODS: Fifty seven patients with established diagnosis or suspicion of CF were studied. The simultaneous identification of 20 mutations and the normal delta F508 allele was done using polymerase chain reactions with a commercial assay. RESULTS: Eight mutations were found. Fifty patients fulfilled diagnostic criteria proposed by the Consensus Panel of the CF Foundation and 66% of alleles were identified in this group. delta F508 mutation was found in 45%. We did not identify mutations in any of the remaining 7 patients. CONCLUSIONS: Our results suggest that the majority of undetected mutations are associated with atypical phenotypes or that some patients in this series could have other diseases. We recommend to include mutation analysis in the evaluation of Chilean patients with CF. It is useful to establish prognosis and genetic counselling.

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

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%). Four (1%) had hypothyroidism, 23 a subclinical hypothyroidism (5.6%) and one (0.2%) had hyperthyroidism. In 87 subjects (21.2%) at least one of the antibodies was positive. Positive anti thyroid antibodies were found in 14 of 28 subjects (50%) with abnormal thyroid hormone levels, compared with 73 of 382 subjects (19.1%) with normal thyroid hormone levels. Thyroid dysfunction was twice as frequent in women than in men. CONCLUSIONS: In this sample, a 6.8% prevalence of abnormal thyroid function tests was detected.

Urinary vasodilator and vasoconstrictor angiotensins during menstrual cycle, pregnancy, and lactation.

Since normal human pregnancy is characterized by normotension in the face of an increased renin-angiotensin-aldosterone system (RAAS), we evaluated the temporal pattern of urinary excretion of a novel vasodilator within this system, angiotensin-(1-7) (Ang-[1-7]), during the menstrual cycle, pregnancy, and lactation. The urinary profiles of Ang I, Ang II, human chorionic gonadotropin, 17beta-estradiol, and progesterone were also determined. During the menstrual cycle, urinary Ang-(1-7) and Ang II remained stable (mean cycle value: 94.6 +/- 11.3 and 11.4 +/- 1.1 pmol/g of creatinine, respectively) in nine females. In 10 normal pregnant women, urinary Ang-(1-7) and Ang II increased throughout gestation, averaging 1499.8 +/- 310 and 224.4 +/- 58 pmol/g of creatinine, respectively (p < 0.05) at wk 35 and falling during lactation to 394.0 +/- 95 and 65.7 +/- 20 pmol/ g of creatinine (p < 0.05), respectively. The Ang-(1-7)/Ang II ratio was unchanged in the different reproductive periods. During the menstrual cycle, Ang II and Ang-(1-7) correlated with 17beta-estradiol and progesterone using multivariate analysis (r = 0.31, p < 0.001) and r = 0.28, p < 0.02, respectively). During gestation, 17beta-estradiol and progesterone correlated with urinary Ang-(1-7) (r = 0.48, p < 0.001 and r = 0.47, p < 0.001, respectively) and Ang II (r = 0.24, p < 0.03 and r = 0.25, p < 0.03, respectively); by multiple regression, only Ang-(1-7) correlated with both steroids (r = 0.49,p < 0.001). The progressive rise of Ang-(1-7) throughout gestation, probably modulated by estrogen and progesterone, suggests a physiologic counterregulation within the RAAS.

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.

Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology.

There is evidence that primary aldosteronism (PA) may be common in patients with essential hypertension (EH) when determinations of serum aldosterone (SA), plasma renin activity (PRA), and the SA/PRA ratio are used as screening. An inherited form of primary hyperaldosteronism is the glucocorticoid-remediable aldosteronism (GRA) caused by an unequal crossing over between the CYP11B1 and CYP11B2 genes that results in a chimeric gene, which has aldosterone synthase activity regulated by ACTH. The aim of this study was to evaluate the prevalence of PA and the GRA in 305 EH patients and 205 normotensive controls. We measured SA (1-16 ng/dL) and PRA (1-2.5 ng/mL x h) and calculated the SA/PRA ratio in all patients. A SA/PRA ratio level greater than 25 was defined as being elevated. PA was diagnosed in the presence of high SA levels (>16 ng/dL), low PRA levels (<0.5 ng/mL x h), and very high SA/PRA ratio (>50). Probable PA was diagnosed when the SA/PRA ratio was more than 25 but the other criteria were not present. A Fludrocortisone test was done to confirm the diagnosis. GRA was differentiated from other forms of PA by: the aldosterone suppression test with dexamethasone, the high levels of 18-hydroxycortisol, and the genetic detection of the chimeric gene. In EH patients, 29 of 305 (9.5%) had PA, 13 of 29 met all the criteria for PA, and 16 of 29 were initially diagnosed as having a probable PA and confirmed by the fludrocortisone test. Plasma potassium was normal in all patients. The dexamethasone suppression test was positive for GRA in 10 of 29 and 18-hydroxycortisol levels were high in 2 of 29 patients who had also a chimeric gene. In normotensive subjects, 3 of 205 (1.46%) had PA, and 1 of 205 had a GRA. In summary, we found a high frequency of normokalemic PA in EH patients. A high proportion of PA suppressed SA with dexamethasone, but only a few had a chimeric gene or high levels of 18-hydroxycortisol. These results emphasize the need to further investigate EH patients.

High prevalence of thyroid abnormalities in a Chilean psychiatric outpatient population.

The aim of the present study was to establish the prevalence of thyroid disturbances in patients consulting for panic and mood disorders. These data may be relevant because thyroid functional alterations affect the success of treatment in these pathologies. We studied prospectively 268 psychiatric outpatients (204 females and 64 males) diagnosed by DSM-IV criteria. We excluded patients with addictive disorders and major medical disease. We measured TSH, Free T4 (FT4) and antimicrosomal antibodies (AMA). We diagnosed classical hypothyroidism when the TSH value was >10 microUI/ml (NV=0.25-4.3) and subclinical hypothyroidism when the TSH value was between 5-10 microUI/ml. Hyperthyroidism was diagnosed when FT4 >1.4 (NV=0.8-1.4), the TSH suppressed and the radioiodine uptake >20% (NV=5-15). Positive antimicrosomal antibodies (AMA) titres were >1:100 dilution. Hypothyroidism was diagnosed in 26/268 patients (9.7%); 10 cases corresponded to the classical form (38.5%) and 16 cases to the subclinical form (61.5%). Hyperthyroidism was found in 6/268 patients (2.2%). Normal thyroid function with positive AMA was found in 28/268 patients (10.4%). Hypothyroidism was more common in patients with mood disorders, and hyperthyroidism in patients with panic disorders. Patients with panic disorder had significant higher levels of FT4. The prevalence of positive AMA, hypothyroidism and hyperthyroidism was higher in women than men. We found a high frequency of thyroid abnormalities in a psychiatric outpatient population. These data suggests that routine evaluation of thyroid function should be considered in patients consulting for mood and panic disorders.

[Excess of mineralocorticoids in essential hypertension: clinical-diagnostic approach]. / Exceso de mineralocorticoides en hipertensos esenciales: enfoque clínico-diagnóstico.

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%. 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 +/- 7.6 and 9.9 +/- 5.1 ng/dl respectively; p = 0.04). Plasma renin activity was lower in hypertensives than controls (1.42 +/- 1.28 and 1.88 +/- 1.39 ng/ml/b respectively; p < 0.001). Thus, plasma aldosterone/plasma renin activity ratio was higher in hypertensives (13.8 +/- 13.5 and 8.3 +/- 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%) and 1/168 normotensive subject (0.6%). 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.

[Measurement of 17 OH progesterone in blood in Chilean newborns: antecedents for implementing a grogram for the neonatal detection of congenital adrenal hyperplasia]. / Medición de 17-OH progesterona sanguínea en recién nacidos chilenos: antecedentes para implementar un programa de detección neonatal de hiperplasia suprarrenal congénita.

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%. Among these newborns with elevated 17OHP, 66% had a birth weight below 1.5 kg and 5.8%, a birth weight between 1.5 and 2.5 kg. The cost per reported result was US $ 1. 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 (Rev Méd Chile 2000; 128: 1113-18).

[Detection of thyroglobulin autoantibodies and potential interference with serum thyroglobulin measurement]. / Autoanticuerpos anti-tiroglobulina: detección y posible interferencia en la medición de tiroglobulina en suero.

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%). Of these, 65 had a recuperation that fluctuated between 1 and 80%. 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% than in sera with a recuperation of less than 80% (12.7 +/- 1.7 and 5.9 +/- 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.

[Capacity to predict a recurrence of lupus erythematosus using double-stranded anti-DNA antibodies and Farr technique]. / Capacidad de predecir una recaída de lupus eritematoso generalizado, mediante anticuerpos anti-DNA de hebra doble, por la técnica de Farr.

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% 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 17 +/- 14 months. RESULTS: Anti-dsDNA levels were 3 +/- 2.5 IU/ml (range 1-26) in subjects without LED, and 127 +/- 500 IU/ml (range 1-5280) in patients with LED. Sixty subjects had an active SLE and 43 (72%) were Farr positive; in 41 the disease was inactive and 13 (32%) were Farr positive (p < 0.001), OR 5.45. Twelve of the 47 followed patients had a relapse and 10 (83%) were Farr positive. Of those that did not have a relapse, 13 (37%) were Farr positive (p < 0.02, RR 5.22). Six of 15 patients that were followed for more than on year (40%), 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.

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

BACKGROUND: Classically, primary hyperaldosteronism was diagnosed in no more than 1% 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.

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.

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

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 to 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 degrees 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%. CONCLUSIONS: A simplified blood sampling method does not change plasma renin activity values, and the longer enzymatic incubation in people with low plasma renin activity improves both the sensitivity and accuracy of the determination.

[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.

Curva AUC farmacocinética reducida y concentraciones promedio de ciclosporina neoral / Curve AUC reduced pharmacokinetics and midle concentrations of neoral cyclosporine

Con los cambios en la formulación así como en los avances en la monitorización hoy es discutible si basta con los niveles basases o es necesario obtener alguna medición más exacta de la exposición del paciente a la ciclosporina. El objetivo de este trabajo es describir la experiencia inicial de monitorización de ciclosporina en el período post trasplante inmediato y comparar la monitorización con nivel basal vs el Arca bajo la Curva (AUC) tanto total como reducido. Aquellos enfermos que no alcanzaron niveles de 300 ng/ml durante la primera semana fueron malos absorbedores y necesitaron una dosis mayor que los que respondieron precozmente. El nivel basal fue un mal indicador de la exposición del enfermo a la ciclosporina, ya que al comparar ambas determinaciones se obtiene una relación de 0.284 (NS). Al correlacionar el AUC promedio con el AUC reducido se observa una correlación de 0.917 (p