Browsing by Author "Rojas, A"
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- Item11 beta-hydroxysteroid dehydrogenase activity in patients with hypertension and low plasma renin activity(2002) Mosso, L; Carvajal, C; Campino, C; Rojas, A; Gonzalez, A; Barraza, A; Montero, J; Fardella, C; NCD Risk Factor Collaboration (NCD-RisC)Background: Half of hypertensive patients with, low plasma renin activity have a primary hyperaldosteronism. Among the remaining half 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) deficiency plays all important role. This enzyme catalyzes the conversion of cortisol to cortisone, avoiding the interaction of cortisol with, the mineralocorticoid receptor. If the enzyme fails, cortisol will stimulate sodium and water reabsorption and increase blood pressure. Aim: To determine biochemical alterations, suggestive of 11betaSHSD2 deficiency, in low-renin hypertensive patients. Patients and Methods: Twenty eight hypertensive patients with a plasma renin activity of less than 0.5 ug/ml/h and with a plasma aldosterone of less than 5 ng/dl were studied. Twenty eight normotensive patients were studied as controls. Serum. cortisol (RIA), cortisone (ELISA) and the serum cortisol/cortisone ratio were determined in all of them, between, 9 and 10 AM. Measurements were confirmed by high pressure liquid chromatography. The serum cortisol/cortisone ratio was considered abnormal when its Ln (cortisol/cortisone) value was over 2 standard deviations of the mean. Results: Serum cortisol was higher in hypertensive subjects than in controls (11.1 +/- 3.3 and 9.2 +/- 2.8 mug/dl, respectively; p <0.05). No differences were observed in serum cortisone (3.4 +/- 1.3 and 3.7 +/- 1.2 μg/dl, respectively). Four hypertensive subjects bad all abnormally high Ln (cortisol/cortisone) value (1.86; 1.73; 2.07 and 2.01, considering a normal value of less than 1.61). Conclusions: Four of 28 hypertensive subjects with, low plasma renin activity and aldosterone had biochemical alterations suggestive of 11.1βHSD2 deficiency.
- ItemFree urinary cortisol is elevated in patients with low-renin essential hypertension(2004) Krall, P; Mosso, L; Carvajal, C; Rojas, A; Fardella, CBackground: Glucocorticoids play a key role in blood pressure (BP) control and are associated with hypertension in patients with Cushing's syndrome. A number of reports indicate that cortisol (F) may be involved in etiology of essential hypertension (EH). F can bind to the mineralocorticoid receptor, triggering both sodium and water reabsorption in kidney, increase BP and cause renin suppression. Aim: To evaluate urinary free cortisol (UFF) excretion as a potential intermediate phenotype of essential hypertension and correlate F level with plasma renin activity (PRA) and serum aldosterone (SA). Patients and Methods: We recruited 132 EH patients and 16 normotensive healthy controls. Blood samples and 24 hours urine were collected for PRA, SA and UFF analysis. Differences in UFF excretion between sexes were normalized by urinary creatinine (Creat) excretion. The upper limit of UFF/Creat was determined in normotensives considering the mean value plus 2 standard deviations. According to this value, subjects were classified as having high or normal UFF. Results: In EH patients and in normotensives, the UFF/Creat was 36.9 +/- 17.0 mug/gr and 30.9 +/- 8.8 mug/gr, respectively. The upper limit was set at 48.5 mug/gr. A high UFF/Creat was found in 20/132 EH (15%) patients and 0/16 normotensive subjects. EH patients with high UFF showed lower PRA levels than patients with normal cortisol levels (0.78 +/- 0.47 vs 1.13 +/- 0.66 ng/ml*h, respectively, p = 0.027) and lower SA values (4.52 +/- 1.65 vs 6.34 +/- 3.37 ng/dl, respectively, p = 0.018). There was a negative correlation between UFF and PRA (r = -0.176, p = 0.044) and between UFF and SA (r = -0.183, p = 0.036). Conclusions: We have identified a subgroup of EH patients with increased UFF excretion. Patients with the highest UFF showed lower renin and aldosterone levels. These data suggest a potential influence of cortisol in the genesis of hypertension.
- ItemGenetic variation in P450c11AS in Chilean patients with low renin hypertension(ENDOCRINE SOC, 1996) Fardella, CE; Rodriguez, H; Montero, J; Zhang, GR; Vignolo, P; Rojas, A; Villarroel, L; Miller, WLLow renin hypertension (LRH), which accounts for 10-20% of patients with idiopathic ''essential'' hypertension, bears hormonal similarities to mineralocorticoid-induced hypertension, but elevated mineralocorticoid concentrations have not been found. Some patients with LRH have normal, rather than suppressed, plasma aldosterone concentrations, so that the ratio of aldosterone concentration to PRA (Aldo/PRA) is high, suggesting inappropriately increased aldosterone biosynthesis. We characterized the CYP11B2 gene that encodes the aldosterone synthase, P450c11AS, in hypertensive and control populations in a single clinic in Santiago, Chile. We directly sequenced the entire CYP11B2 gene in 12 patients with LRH, 2 high renin hypertensive controls, and 2 normotensive controls. All sequences were identical, except that 8 of 24 LRH alleles encoded arginine rather than lysine at position 173. The Arg(173) and Lys(173) variants were expressed in transfected MA-10 cells, and their ability to convert deoxycorticosterone to aldosterone was measured; the apparent Michaelis constant (K-m) for Lys(173) was 2.73 mu mol/L; the K-m for Arg(173) was 2.53 mu mol/L. The apparent maximal velocity (V-max) for Lys(173) was 6.5x10(-3) mu g/mL . 24 h; the V-max for Arg(173) was 7.8x10(-3) mu g/mL . 24 h. The first order rate constant, V-max/K-m was 2.38 for Lys(173) and 3.08 for Arg(173). As these values were not significantly different, we sought to determine whether Arg(173) is a polymorphism linked to LRH. We examined position 173 in 52 unselected patients with idiopathic hypertension and 55 normotensive controls by PCR amplification of CYP11B2 exons 3-5 followed by digestion with Bsu36I, which digests the Arg(173) sequence, but not the Lys(173) sequence. More of the hypertensive alleles (39 of 104, 37.5%) than normotensive alleles (25 of 110, 22.5%) carried Arg(173) (chi(2)=5.57; P <0.02). Most of the Arg(173) alleles (31 of 72, 43.1%) were from hypertensive patients with Aldo/PRA below 30, whereas only 5 of 24 (20.8%) Arg(173) alleles were found in patients with Aldo/PRA greater than 30 (chi(2)=3.79; P=0.05) Thus, the Arg(173) variant of CYP11B2 may be linked to LRH in Chilean patients.
- ItemHigh prevalence of undiagnosed primary hyperaldosteronism among patients with essential hypertension(1999) Mosso, L; Fardella, C; Montero, J; Rojas, P; Sanchez, O; Rojas, V; Rojas, A; Huete, A; Soto, J; Foradori, A; NCD Risk Factor Collaboration (NCD-RisC)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 nod 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 of the aldosterone/plasma renin activity ratio was over 50. A probable primary hyperaldosteronism was diagnosed whet? 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.
- ItemNormokalemic primary hyperaldosteronism - A common cause of secondary hypertension.(1999) Mosso, L; Fardella, C; Montero, J; Rojas, P; Sanchez, O; Rojas, A; Soto, J; Foradori, A; Huete, A; NCD Risk Factor Collaboration (NCD-RisC)Recently, some genetic forms of hypertension have been well characterized. These forms can be globally called mineralocorticoid hypertension and are due to different alterations of the renin-angiotensin-aldosterone system (SRAA). Among these, classic primary hyperaldosteronism and its glucocorticoid remediable variety, in which hypertension is secondary to aldosterone production, must be considered. There are also conditions in which mineralocorticoid activity does not depend on aldosterone production. These conditions generate a hyporeninemic hyperaldosteronism, observed in Liddle syndrome, apparent mineralocorticoid hypertension, 11- and 17-hydroxilase deficiency, among others. The detection of these forms of hypertension is only feasible if the renin-angiotensin-aldosterone system is assessed, measuring renin and aldosterone levels. This article reviews these forms of hypertension, their clinical workup and their relevance in the usual hypertensive patients.
- ItemThe A-6G mutation in the angiotensinogen gene is associated to high levels of aldosterone in essential hypertensives(1999) Fardella, C; Zamorano, P; Gomez, L; Oestreicher, E; Pinto, M; Rojas, A; Montero, J; Soto, J; Mosso, L; Foradori, AThe treatment of papillary thyroid carcinoma of less than 10 mm diameter is a matter of controversy. The incidental finding of papillary microcarcinomas in autopsies is frequent and some authors postulate that these tumors are biologically inactive and should only be observed. We report a 21 years old woman with a papillary thyroid cancer of 6x5x5 mm and bilateral paratracheal metastases, that was subjected to a total thyroidectomy. She received 200 mCi of radioiodine. Two years after surgery, a new nodule of 9.6 mm diameter was detected by ultrasound, that was treated with a new dose of 200 mCi of radioiodine. One year later a suprasternal mass of 2 cm diameter and 3 enlarged lymph nodes were detected. She was subjected to a surgical lymph node dissection of the neck and the biopsy confirmed the presence of cancer. She received a new dose of 300 mCi of radioiodine. The mother of the patient had a 7 mm thyroid nodule that was also a papillary carcinoma.
- ItemThe terminally ill patient(2000) Bravo, M; Echeverria, C; Goic, A; Kottow, M; Lavados, M; Mosso, L; Perez, M; Quintana, C; Rojas, A; Rosselot, E; Serani, A; Taboada, P; Trejo, C; Soc Med Santiago; NCD Risk Factor Collaboration (NCD-RisC)The classification of a patient as terminally ill is based on an expert diagnosis of a severe and irreversible disease and the absence of an effective available treatment, according to present medical knowledge. Terminal diseases must not be confused with severe ones, since the latter may be reversible with an adequate and timely treatment. The physician assumes a great responsibility at the moment of diagnosing a patient as terminally ill. The professional must assume his care until the moment of death. This care must be oriented to the alleviation of symptoms and to provide the best possible quality of life. Also, help must be provided to deal with personal, legal and religious issues that may concern the patient.