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Browsing by Author "Montero, J"

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Biochemical and genetic characterization of 11 beta- hydroxysteroid dehydrogenase type 2 in low-renin essential hypertensives
(LIPPINCOTT WILLIAMS & WILKINS, 2005) Carvajal, CA; Romero, DG; Mosso, LM; Gonzalez, AA; Campino, C; Montero, J; Fardella, CE
Background The 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) catalyzes the conversion of cortisol M to cortisone (E), avoiding the interaction of cortisol with the mineralocorticoid receptor. If it fails, cortisol will stimulate sodium and water reabsorption, increasing the intravascular volume that suppresses renin and secondarily increase the blood pressure.
Critical appraissal: Should atenolol be the first choice for primary hypertension? Carlberg B, Samuelsson O, Lindholm L. Atenolol in hypertension: is it a wise choice? Lancet 2004; 364 : 1684-89
(SOC MEDICA SANTIAGO, 2005) Neumann, I; Montero, J
Bdckground: Atenolol is one of the most widely used beta blockers clinically, and has often been used as a reference drug in randomized controlled trials of hypertension. However questions have been raised about atenolol as the best reference drug for comparisons with other antihypertensives. Thus, our aim was to systematically review the effect of atenolol on cardiovascular morbidity and mortality in hypertensive patients. Methods. Reports were identified through searches of The Cochrane Library, MEDLINE, relevant textbooks, and by personal communication with established researchers in hypertension. Randomized controlled trials that assessed the effect of atenolol on cardiovascular morbidity or mortality in patients with primary hypertension were included. Findings. We identified four studies that compared atenolol with placebo or no treatment, and five that compared atenolol with other antihyperensive drugs. Despite major differences in blood pressure lowering, there were no outcome differences between atenolol and placebo in the four studies, comprising 6,825 patients, who were followed up for a mean of 4.6 years on all-cause mortality (relative risk 1.01 [95% Cl 0.89-1.15]), cardiovascular mortality (0.99 [0.83-1.18]), or myocardial infarction (0.99 [0.83-1.19]). The risk of stroke, however tended to be lower in the atenolol than in the placebo group (0.85 [0.72-1.01]). When atenolol was compared with other antihypertensives, there were no major differences in blood pressure lowering between the treatment arms. Our meta-analysis showed a significantly higher mortality (1.13 [1.02-1.25]) with atenolol treatment than with other active treatment, in the five studies comprising 17,671 patients who were followed up for a mean of 4.6 years. Moreover, cardiovascular mortality also tended to be higher with atenolol treatment than with other antihypertensive treatment. Stroke was also more frequent with atenolol treatment. Interpretation: Our results cast doubts on atenolol as a suitable drug for hypertensive patients. Moreover they challenge the use of atenolol as a reference drug in outcome trials in hypertension.
Evidences for mineralocorticoid excess in essential hypertension
(2000) Cortes, P; Fardella, C; Oestreicher, E; Gac, H; Mosso, L; Soto, J; Foradori, A; Claverie, X; Ahuad, J; Montero, J
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 a 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/h 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.
Genetic studies in dexamethasone supressible aldosteronism.
(2001) Fardella, C; Pinto, M; Mosso, L; Oestreicher, E; Montero, J
We report two women presenting with parathyroid cysts. A 20 years old woman presented with goiter and a cystic lesion in the left thyroid lobe was identified on ultrasound examination and CAT scan. The patient had hypercalcemia and elevated PTH levels. The content of the cyst, obtained by needle aspiration, had an extremely high PTH concentration. The patient was operated, removing the cyst and a remaining thymus. Pathological study confirmed the diagnosis of a parathyroid cyst. An 11 years old girl presented with a mass in the left thyroid lobe. An ultrasound examination disclosed the presence of a cystic nodule. The patient was otherwise asymptomatic and laboratory work up was normal. The patient was operated and pathological examination of the surgical piece revealed a parathyroid cyst.
Genetic study of patients with dexamethasone-suppressible aldosteronism without the chimeric CYP11B1/CYP11B2 gene
(ENDOCRINE SOC, 2001) Fardella, CE; Pinto, M; Mosso, L; Gomez Sanchez, C; Jalil, J; Montero, J
Glucocorticoid-remediable aldosteronism is an inherited disorder caused by a chimeric gene duplication between the CYP11B1 (11 beta -hydroxylase) and CYP11B2 (aldosterone synthase) genes. The disorder is characterized by hyperaldosteronism and high levels of 18-hydroxycortisol and 18-oxocortisol, which are under ACTH control. The diagnosis of glucocorticoid-remediable aldosteronism had been traditionally made using the dexamethasone suppression test; however, recent studies have shown that several patients with primary aldosteronism and a positive dexamethasone suppression test do not have the chimeric CYP11B1/CYP11B2 gene. The aim of this work was to evaluate whether other genetic alterations exist in CYP11B genes (gene conversion in the coding region of CYP11B1 or in the promoter of CYP11B2) that could explain a positive dexamethasone suppression test and to determine another genetic cause of glucocorticoid-remediable aldosteronism. We also evaluated the role of 18-hydroxycortisol. as a specific biochemical marker of glucocorticoid-remediable aldosteronism. We studied eight patients with idiopathic hyperaldosteronism, a positive dexamethasone suppression test, and a negative genetic test for the chimeric gene. In all patients we amplified the CYP11B1 gene by PCR and sequenced exons 3-9 of CYP11B1 and a specific region (-138 to -284) of CYP11B2 promoter. We also measured the levels of 18-hydroxycortisol, and we compared the results with those found in four subjects with the chimeric gene. None of eight cases showed abnormalities in exons 3-9 of CYP11B1, disproving a gene conversion phenomenon. In all patients a fragment of 393 bp corresponding to a specific region of the promoter of CYP11B2 gene was amplified. The sequence of the fragment did not differ from that of the wild-type promoter of the CYP11B2 gene. The 18-hydroxycortisol levels in the eight idiopathic hyperaldosteronism patients and four controls with chimeric gene were 3.9 +/- 2.3 and 21.9 +/- 3.5 nmol/liter, respectively (P < 0.01). In summary, we did not find other genetic alterations or high levels of 18-hydroxycortisol that could explain a positive dexamethasone suppression test in idiopathic hyperaldosteronism. We suggest that the dexamethasone suppression test could lead to an incorrect diagnosis of glucocorticoid-remediable aldosteronism.
Genetic 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, WL
Low 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.
Glucocorticoid treatable hypertension. Report of one case
(1997) Montero, J; Fardella, C; Mosso, L
Lately, a series of hypertensive syndromes of unknown etiology that respond to new forms of therapy, have been described One of these is glucocorticoid remediable hypertension, that evolves with suppressed plasma renin activity and normal or high serum aldosterone levels, that lead to an aldosterone/plasma renin activity ratio over 30. We report a 45 years old woman with a severe hypertension despite the use of antihypertensive medications. She had a plasma renin activity of less than 0.3 ng/ml/h, normal serum aldosterone levels (10 ng/ml) and thus a high aldosterone/plasma renin activity ratio. She had normal serum potassium and sodium levels. Due to the bad results of conventional antihypertensive medications, a treatment with dexamethasone was started that normalized blood pressure and allowed to discontinue other antihypertensive medications. This type of hypertensive must besought since non conventional treatments could be used for refractory hypertensive syndromes.
Improving physical fitness and emotional well-being in adolescents of low socioeconomic status in Chile: results of a school-based controlled trial
(OXFORD UNIV PRESS, 2005) Bonhauser, M; Fernandez, G; Puschel, K; Yanez, F; Montero, J; Thompson, B; Coronado, G
Regular physical activity is associated with a reduced risk of all-cause mortality, and mortality due to cardiovascular disease and cancer. Among adolescents, physical activity is associated with benefits in the prevention and control of emotional distress, and improvement of self-esteem. Countries in transitional epidemiological scenarios, such as Chile, need to develop effective strategies to improve physical activity as a way to face the epidemic of chronic diseases. The objective of this study was to evaluate the effects of a school-based physical activity program on physical fitness and mental health status of adolescents living in a low socioeconomic status area in Santiago, Chile. A quasi-experimental design was used to evaluate the effects of the program over one academic year. The study included 198 students aged 15 years old. Two ninth grade classes were randomly selected as the intervention group, with two classes of the same grade as controls. A social planning approach was used to develop the intervention. The program was designed and implemented based on student preferences, teachers' expertise and local resources. Changes in physiological and mental health status were assessed. After the intervention, maximum oxygen capacity achieved a significant increase of 8.5% in the intervention versus 1.8% in the control group (p < 0.0001). Speed and jump performance scores improved significantly more in the intervention versus the control group (p > 0.01). Anxiety score decreased 13.7% in the intervention group versus 2.8% in the control group (p < 0.01), and self-esteem score increased 2.3% in the intervention group and decreased 0.1% in the control group after the end of the program (p < 0.0001). No significant change was observed in the depressive score. Student participation and compliance with the program was > 80%. To conclude, a school-based program to improve physical activity in adolescents of low socioeconomic status, obtained a high level of participation and achieved significant benefits in terms of physical fitness and mental health status.
T235 Variant of the angiotensinogen gene and blood pressure in the Chilean population
(LIPPINCOTT WILLIAMS & WILKINS, 1998) Fardella, CE; Claverie, X; Vignolo, P; Montero, J; Villarroel, L
Background The angiotensinogen gene has recently been linked to essential hypertension, A variant within this gene, encoding threonine rather than methionine at amino acid position 235, was associated with essential hypertension, However, results of new studies have not confirmed this association, suggesting that ethnic differences may explain the different results.
The 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, A
The 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.

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