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C Fardella

Publications and source records attributed to C Fardella.

At least 19 recordsLinked to original sources
PubMed2004

Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene polymorphism in humans.

Neutral endopeptidase (NEP) hydrolyses angiotensins (Ang) I and II and generates angiotensin-(1-7) [Ang-(1-7)]. In humans, the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism determined plasma ACE levels by 40%. In rats, a similar polymorphism determines ACE levels which are inversely associated to NEP activity. The objective of this study is to evaluate the relationship between ACE expression and plasma NEP activity in normotensive subjects and in hypertensive patients. In total, 58 consecutive patients with hypertension, evaluated in our Hypertension Clinic, were compared according to their ACE I/D genotypes with 54 control subjects in terms of both plasma ACE activity and NEP activities. Plasma ACE activity was elevated 51 and 70% in both DD ACE groups (normotensives and hypertensives) compared with their respective ID and II ACE groups (P<0.001). A significant effect of the ACE polymorphism and of the hypertensive status on ACE activity was observed (P<0.001). In normotensive DD ACE subjects, NEP activity was 0.30+/-0.02 U/ml, whereas in the normotensive II ACE and in the normotensive ID ACE subjects NEP activity was increased 65 and 48%, respectively (P<0.001). In the hypertensive DD ACE patients, NEP activity was 0.47+/-0.03 U/mg. An effect of the I/D ACE genotypes on NEP activity (P<0.04) and an interaction effect between the I/D ACE genotype and the hypertensive status were also observed (P<0.001). These results are consistent with a normal and inverse relationship between the ACE polymorphism and NEP activity in normotensive humans (as is also observed in rats). This normal relationship is not observed in hypertensive patients.

Analysis of Variance↗
PubMed2001

Serum 18-hydroxycortisol in primary aldosteronism, hypertension, and normotensives.

This study reports the determination of plasma 18-hydroxycortisol (18-OHF) using a new and easy enzyme-linked immunosorbent assay (ELISA) method in primary aldosteronism and compares the values found in essential hypertensives and normotensive controls. In primary aldosteronism, we evaluated usefulness of plasma 18-OHF determination and the dexamethasone suppression test in the diagnosis of glucocorticoid-remediable aldosteronism using the genetic test as the gold standard. We studied 31 primary aldosteronism patients, 101 essential hypertensives, and 102 healthy normotensive controls. The plasma 18-OHF was measured using a biotin-avidin enzyme-linked assay by a new and purified polyclonal antibody. The 18-OHF value in primary aldosteronism was 6.3+/-8.05 nmol/L; this value is significantly higher than the value found in essential hypertensives and normotensive controls (2.81+/-1.42 and 2.70+/-1.41 nmol/L, respectively; P<0.0005). In primary aldosteronism, 4 of 31 patients had 18-OHF levels that were 10 times higher than the normal upper limit (2.983 nmol/L). The dexamethasone suppression test in primary aldosteronism patients was positive (serum aldosterone <4 ng/dL) in 13 of 31 cases. A chimeric CYP11B1/CYP11B2 gene was demonstrated in 4 primary aldosteronism patients, corresponding to the same cases that had higher level of 18-OHF. In conclusion, plasma 18-OHF determination by this ELISA method is reliable for detecting glucocorticoid-remediable aldosteronism, and it does so better than the dexamethasone suppression test.

Adult↗
PubMed2001

[High prevalence of subclinical thyroidal disease among individuals attended in health control].

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.

Adolescent↗
PubMed2001

[Panic disorder and hyperthyroidism. Report of 2 cases].

In two females aged 27 and 32 years old, an aggravation of their panic disorder coincided with the appearance of clinical signs of hyperthyroidism. The clinical diagnosis was confirmed with the finding of raised thyroid hormone levels and undetectable TSH levels. These two cases highlight the importance of routine thyroid function assessment in patients with panic disorder, mainly in those with partial response to medications or when symptoms aggravate, despite an adequate treatment.

Adult↗
PubMed2000

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.

Adolescent↗
PubMed2000

[Excess of mineralocorticoids in essential hypertension: clinical-diagnostic approach].

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.

Adult↗
PubMed1999

Persistent hypokalemia after successful adrenalectomy in a patient with Cushing's syndrome due to ectopic ACTH secretion: possible role of 11beta-hydroxysteroid dehydrogenase inhibition.

Ectopic ACTH secretion is characterized by a high incidence of hypokalemia. The pathophysiology of hypokalemia has not been totally clarified, although it has been postulated that excessive amounts of adrenal steroids may play a role, as well as a possible role of the inhibition of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD). This enzyme normally converts cortisol to cortisone avoiding the mineralocorticoid action of cortisol. We present a patient with ectopic ACTH secretion due to a metastatic carcinoid tumor. The clinical picture was characterized by maintained hypokalemia (1.4 mmol/l) resistant to potassium, spironolactone and ketoconazole administration. A bilateral adrenalectomy was performed but the hypokalemia persisted while he was receiving a physiological dose of cortisol. Eight days after adrenalectomy cortisol was replaced by an equivalent dose of dexamethasone. This change was followed by a rapid and persistent normalization of hypokalemia suggesting a mineralocorticoid effect of cortisol. In conclusion, the origin of hypokalemia in our patient with ectopic ACTH secretion was secondary to cortisol. We postulate that this peculiar effect of cortisol could have happened if an inhibition of 11beta-OHSD occurred.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

A(-6)G variant of angiotensinogen gene and aldosterone levels in hypertensives.

Recently, a novel mutation in the promoter region of the angiotensinogen gene that involves the presence of an adenine instead of a guanine 6 bp upstream from the transcription initiation site (A(-6)G) has been shown to induce an increase in gene transcription. The aim of this study was to determine the prevalence of the A(-6)G mutation in essential hypertensive patients and to correlate it with aldosterone and renin activity levels. We studied 191 hypertensives. We measured levels of aldosterone (plasma and urinary) and plasma renin activity. We determined the variants A and G using a mutagenically separated polymerase chain reaction technique. In 191 hypertensives, the A variant was detected in 266 of 382 (69.6%) and the G variant in 116 of 382 alleles (30.4%). Plasma aldosterone was significantly higher in patients homozygous for AA than in those homozygous for GG (369+/-208 versus 246+/-142 pmol/L). Urinary aldosterone was significantly higher in homozygous AA than in AG or GG patients (62.4+/-39.4 versus 50.8+/-25.2 and 37.4+/-22.3 nmol/d, respectively). When the patients were grouped according to the presence or absence of the A allele, the aldosterone levels and the plasma aldosterone/plasma renin activity ratio were significantly higher in patients with the A allele. The presence of the A variant was associated with higher levels of aldosterone. These results suggest that the presence of the A variant could determine the appearance of arterial hypertension through higher transcription activity of the angiotensinogen gene and concomitant aldosterone production.

Aged↗
PubMed1999

[Prevalence of the 185Ag deletion of the BRCA1 gene in Chilean women with breast neoplasm].

BACKGROUND: The most important identified pathogenic factor for breast cancer is the presence of mutations in BRCA1 gene. These are associated with familial breast cancer in up to 80% of cases. The most frequent mutation of BRCA1 gene in Caucasian populations is the exon 2 185AG deletion. AIM: To study the presence of 185AG deletion in Chilean women with sporadic or familial breast cancer. PATIENTS AND METHODS: We studied 15 women with familial breast cancer, in whom at least one close relative was affected, and 40 women with sporadic breast cancer. In genomic DNA obtained from a blood sample, an allele specific polymerase chain reaction was done. This reaction allows the identification of 185AG deletion and uses two pairs of primers. One for the native form that renders a 118 base pairs product and one for the deletion that renders a 170 base pairs product, both with a respective 280 base pairs internal control. RESULTS: The diagnosis of breast cancer was done at 40 +/- 5 and 65 +/- 10 years old in women with familial and sporadic breast cancer, respectively. In none of the samples, the amplification of the 170 base pairs band that corresponds to 185AG deletion, was obtained. In both groups, the product of the amplification was the 118 base pairs band, that corresponds to the native form of BRCA1 gene. The polymerase chain reaction was optimized for a duration of 90 minutes. CONCLUSIONS: 185AG deletion of BRCA1 gene was not detected in this group of Chilean women with sporadic or familial breast cancer.

Adult↗
PubMed1999

[Cushing syndrome by ectopic ACTH secretion: analysis of the physiopathologic mechanism of hypokalemia. Report of two cases].

We report a 42 years old male and a 66 years old female with a Cushing syndrome caused by ectopic ACTH secretion secondary to a carcinoid tumor. These patients had both severe hypokalemia, resistant to medical treatment and that subsided with bilateral adrenalectomy and supplementation with dexametasone. Cushing syndrome caused by ectopic ACTH secretion is characterized by a severe and rapidly evolving hypercortisolism. Hypokalemia is present in 90% of cases and is probably caused by a defect in 11 beta hydroxysteroid dehydrogenase, that limits the binding of cortisol to aldosterone receptor, metabolizing it to cortisone. Therefore, this alteration will increase the mineralocorticoid action of cortisol.

ACTH Syndrome, Ectopic↗
PubMed1999

[High prevalence of undiagnosed primary hyperaldosteronism among patients with essential hypertension].

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.

Aldosterone↗
PubMed1998

[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 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.

Adolescent↗
PubMed1997

[Adrenal macrotumor diagnosed by computed tomography. Clinical experience of 33 cases].

BACKGROUND: Adrenal tumors of more than 6 cm diameter, also called macrotumors, cause diagnostic and therapeutic problems. AIM: To perform an analysis of adrenal macrotumors diagnosed by CAT scan between 1984 and 1995. PATIENTS AND METHODS: Thirty three patients aged 9 to 86 years old, 15 female, with an adrenal macrotumor diagnosed by CAT scan, were analyzed. RESULTS: Thirty percent of tumors were functioning (70% secreted cathecolamines and 30% cortisol). Eighty two percent had an adrenal localization and 18% were para-adrenal. Thirty four percent were malignant. These tumors were mostly non functioning, 70% occurred in men and 67% were metastatic. CONCLUSIONS: Most adrenal macrotumors in this series were non functioning and 36% were malignant.

Adolescent↗
PubMed1997

[Molecular diagnosis of salt wasting congenital adrenal hyperplasia, caused by deficit of 21-hydroxylase, in the Chilean population].

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.

Adrenal Hyperplasia, Congenital↗
PubMed1997

[Relevance of the thyroid function assessment in psychiatric patients].

BACKGROUND: Thyroid dysfunction is frequent in psychiatric outpatients and the correction of their endocrine abnormalities seems to improve the response to psychopharmacologic treatment. AIM: To retrospectively explore the frequency of thyroid abnormalities in psychiatric outpatients. MATERIAL AND METHODS: Clinical charts and thyroid assessment of 102 psychiatric patients aged 40.8 +/- 15 years old (28 male) seen between April 1995 and September 1996 were reviewed. Endocrine diagnosis was made according to international criteria and psychiatric diagnosis was made by a single psychiatrist following DSM IV criteria. RESULTS: Forty patients (39.2%) had thyroid abnormalities. Thirteen (12.7%) had a diagnosis of thyroid problems and were in treatment before they came to the psychiatric clinic. Sixteen patients had hypothyroidism (40%), seven had subclinical hypothyroidism (17.5%), 12 were euthyroid but had goiter or positive thyroid antibodies (30%) and 5 individuals had hyperthyroidism (12.5%). The most frequent thyroid abnormality was the presence of positive thyroid antibodies in 16 cases (15.7%). No specific association was found between psychiatric and endocrine diagnoses. CONCLUSIONS: The design of this study prevents to draw conclusions about prevalence of thyroid alterations in psychiatric patients. Nevertheless results support the need for routine thyroid assessment in this specific population.

Bipolar Disorder↗
PubMed1997

[Hypertension treatable with glucocorticoids: report of a case].

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 hypertension must be sought since non conventional treatments could be used for refractory hypertensive syndromes.

Aldosterone↗
PubMed1995

Intracellular calcium and blood pressure: comparison between primary hyperparathyroidism and essential hypertension.

Intracellular calcium has been reported to be increased in essential hypertension, and thought to play a role in its genesis through facilitation of vascular smooth muscle contraction. Since hypertension is more prevalent in primary hyperparathyroidism, intracellular calcium may also be increased in this condition. To investigate whether the hyperparathyroid condition, i.e., hypercalcemia and increased PTH per se, could be associated with high intracellular calcium, we measured intracellular calcium in platelets with the Quin-2 AM fluorometric method in 11 normotensive patients with primary hyperparathyroidism, 15 patients with essential hypertension, and 18 normal controls, all matched for age and sex. We repeated the measurements in 9 of the hyperparathyroid patients after successful surgery. We found that intracellular calcium was higher in normotensive patients with primary hyperparathyroidism than in normal controls (198 +/- 24 vs 113 +/- 11 nM, p < 0.05), but lower than in patients with essential hypertension (198 +/- 24 vs 286 +/- 38 nM, p < 0.05). Successful removal of a parathyroid adenoma decreased intracellular calcium from 215 +/- 22 to 116 +/- 19 nM, (p < 0.01). In the patients with primary hyperparathyroidism, intracellular calcium was strongly correlated with the levels of PTH (r = 0.87, p < 0.01), but not with the total serum calcium levels (r = 0.04, NS). The decrease in intracellular calcium after parathyroidectomy was also strongly correlated with the decrease in PTH (r = 0.84, P < 0.01), but not with the decrease in total serum calcium (r = 0.16, NS). In the patients with essential hypertension, intracellular calcium correlated well with systolic (r = 0.69, p < 0.01), diastolic (r = 0.76, p < 0.01) and especially mean arterial pressure (r = 0.86, P < 0.01). There was no correlation between blood pressure and intracellular calcium in the patients with primary hyperparathyroidism. We conclude that normotensive patients with primary hyperparathyroidism, as well as patients with essential hypertension, can have increased concentrations of intracellular calcium in platelets. The correction of the hyperparathyroid condition normalizes intracellular calcium concentration. The close correlation between PTH and intracellular calcium suggests that PTH may act as a ionophore for calcium entry into cells. Whether the increased levels of intracellular calcium may reflect a pre-hypertensive condition in normotensive patients with primary hyperparathyroidism remains to be determined.

Adenoma↗