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Biomedical subjects

E L Bravo

Publications and source records attributed to E L Bravo.

At least 37 records · Page 2Linked to original sources
PubMed1995

Production, characterization, and expression of neuropeptide Y by human pheochromocytoma.

Neuropeptide Y (NPY) levels are increased in plasma and tumors of patients with pheochromocytoma. The present study was designed to evaluate plasma and tissue NPY levels simultaneously as well as to study its release and expression in patients with either adrenal or extraadrenal pheochromocytomas. Plasma NPY levels were higher (P < 0.01) in patients with adrenal tumors than in matched normal subjects and patients with extraadrenal tumors. NPY levels were also higher (P < 0.05) in adrenal than in extraadrenal tumors. Bioactive NPY (1-36) was the predominant form in plasma and tumors of patients with adrenal pheochromocytomas. In contrast, patients with extraadrenal pheochromocytomas had an abundance of NPY fragments. NPY mRNA was abundant in 11 of 13 adrenal tumors but in only 1 of 6 extraadrenal tumors. Moreover, NPY was coreleased with NE with manipulation of adrenal but not extraadrenal tumors. These findings indicate that increased NPY gene expression in adrenal pheochromocytomas accounts for the greater biosynthesis and storage of NPY in these tumors and that increased release of NPY results in elevated plasma NPY. Factors regulating NPY gene expression in pheochromocytoma and the role of NPY in the clinical manifestations of the disease remain to be elucidated.

Adolescent↗
PubMed1994

Fentanyl stimulates atrial natriuretic peptide secretion.

The effects of fentanyl on ultrastructure, protein biosynthesis, and atrial natriuretic peptide (ANP) secretion were studied in neonatal rat cardiomyocytes (CM). Ventricles from 2-day-old American Wistar rats were digested with 1% collagenase in perfusion buffer. Eight hundred thousand to 1.0 million cells/ml were incubated in tissue culture media, to which fentanyl citrate (Sublimaze) was added in a dose of 10-50 ng/ml. Fentanyl increased the spontaneous CM beating rate, which became rather fibrillary in nature. Protein biosynthesis also increased in a time-related manner. Simultaneous incubation with naloxone (10(-6) M) did not alter the beating rate or protein synthesis. Ultrastructurally, several criteria of myocyte growth were observed: an increase in myofilaments and the appearance of newly formed organized sarcomeres, which were preceded by an increase in the ribosomes and cisternae of rough endoplasmic reticulum, and the appearance of large, adult-type mitochondria with increased matrix granules and long parallel cristae. The latter replaced the elongated thin fetal mitochondria. This was associated with a network of developing sarcoplasmic reticulum and T-tubular system as well as the formation of intercalated discs between the CM. Furthermore, exposure to fentanyl increased ANP immunoreactivity in the culture media while simultaneous incubation with naloxone blocked the effect of fentanyl on ANP secretion. On the other hand, naloxone alone did not alter ANP secretion. Therefore, it could be concluded that fentanyl stimulated protein biosynthesis and ANP secretion as evidenced both biochemically and ultrastructurally. Although the molecular mechanism of ANP secretion by fentanyl is still unclear, yet an opioid receptor mediation could be possible as ANP secretion was blocked by an opioid receptor antagonist (naloxone).

Animals↗
PubMed1994

Diagnostic specificity of serum chromogranin-A for pheochromocytoma in patients with renal dysfunction.

We assessed the clinical utility of serum chromogranin A (CgA) alone and in combination with plasma catecholamines in the diagnosis of pheochromocytoma in patients with mild to moderate renal impairment. The study population consisted of 44 normal subjects, 50 subjects with proven pheochromocytoma, and 82 subjects with hypertension (60 primary and 22 secondary) suspected but not proven to have the disease. In this highly selected group with high disease prevalence (38%), the overall sensitivity, specificity, accuracy, and positive and negative predictive values of serum CgA in the diagnosis of pheochromocytoma were 86%, 74%, 79%, 67%, and 94%, respectively. However, in patients with creatinine clearance less than 1.33 mL/s (80 mL/min), these values dropped to 85%, 50%, 59%, 38%, and 90%, respectively. The combination of plasma catecholamines and CgA provided the best overall specificity (95%), accuracy (88%), and positive predictive value (91%). In patients with a creatinine clearance of more than 1.33 mL/s, the combination gave a specificity of 98%, an accuracy of 89%, and a positive predictive value of 97%. These results show that serum CgA has poor diagnostic specificity in the diagnosis of pheochromocytoma when renal function is impaired. Combining CgA with plasma catecholamines provides a lower sensitivity, but excellent specificity, accuracy, and positive predictive value.

Adrenal Gland Neoplasms↗
PubMed1994

Dietary calcium supplementation prevents the development of hypertension in deoxycorticosterone-salt-treated dogs.

High levels of dietary calcium attenuate the elevation of arterial pressure induced by deoxycorticosterone (DOC)-salt in trained, conscious dogs. This response resulted primarily from the failure of the expected rise in peripheral vascular resistance to develop. In addition, the enhanced pressor sensitivity to norepinephrine and angiotensin II associated with DOC-salt hypertension was normalized by high levels of dietary calcium. These changes could not be explained by changes in serum potassium concentration, plasma catecholamines concentration, or plasma volume. A possible explanation is that high levels of dietary calcium inhibit a parathyroid hypertensive factor that has been observed to be elevated in mineralocorticoid-induced hypertension. This hypothesis requires further studies.

Angiotensin II↗
PubMed1994

Primary aldosteronism. Issues in diagnosis and management.

The clinical manifestations of primary aldosteronism are not distinctive, but additional studies are warranted in certain hypertensive patients, including patients with either spontaneous or diuretic-induced hypokalemia and those with refractory hypertension without an obvious secondary cause. The best test for identifying patients with primary aldosteronism is measuring the aldosterone excretion rate during salt loading. A rate exceeding 14 micrograms/24 hour provides the highest sensitivity and specificity. The presence of hypokalemia and suppressed plasma renin activity provides corroborative evidence but their absence does not preclude the diagnosis. An adenoma is likely in the presence of significant spontaneous hypokalemia (serum potassium concentration < or = 3 mEq/L), a paradoxic decrease in ambulatory plasma aldosterone concentration, and plasma 18-hydroxycorticosterone values equal to or greater than 100 ng/dL. The adrenal CT scan should be considered the initial step in localization. Primary aldosteronism can be associated with severe and drug-resistant hypertension, and maintained hypervolemia is the reason for resistance to therapy. Sustained volume depletion is the most important therapeutic goal for these patients. Medical therapy is indicated for patients with hyperplasia and for patients with bilateral adenomas that may require total bilateral adrenalectomy. Whenever feasible, surgical excision is recommended for unilateral tumors, and cure can be achieved despite prolonged and severe hypertension.

Humans↗
PubMed1994

Pheochromocytoma.

None of the endocrine causes for hypertension is more fascinating and challenging for the clinician than pheochromocytoma. Its protean manifestations can make diagnosis difficult, yet its sinister prognostic implications demand prompt recognition and expert management. Diagnosis depends on clinical suspicion, demonstration of high levels of free catecholamines in the plasma or urine, or high localization of the tumor by appropriate imaging techniques that include CT scanning, MR imaging, and 131I-MIBG scintigraphy. Surgical extirpation is the treatment of choice unless the risk of operation is overwhelming or distant metastasis has already occurred. Successful outcome demands a team approach, taking advantage of the experience, skill, and expertise of the surgeon, anesthesiologist, and internist.

Adrenal Gland Neoplasms↗
PubMed1993

Pheochromocytoma.

Pheochromocytomas cause the most dramatic life-threatening crises in all of endocrinology. Pheochromocytoma is an explosive clinical syndrome that may be characterized by either severe hypertension associated with cerebral, cardiac, and renal complications or hypotension, or even shock and sudden death. Other emergencies include lactic acidosis, hypoglycemia, hypercalcemic crisis, severe hypokalemic alkalosis, and acute bowel obstruction due to bowel ischemia, necessitating prompt surgical intervention. Better understanding of the mechanisms of catecholamine action and the pathophysiology of pheochromocytoma and the availability of various treatment modalities have made successful management more promising than ever before.

Adrenal Gland Neoplasms↗
PubMed1992

Differences in left ventricular structural and functional changes between pheochromocytoma and essential hypertension. Role of elevated circulating catecholamines.

Experimental findings suggest that catecholamines increase protein synthesis and play a role in cardiac hypertrophy. We hypothesize that elevated circulating plasma catecholamines in pheochromocytoma influence cardiac structural and functional remodeling. We compared 15 patients with surgically proven pheochromocytoma and 15 with untreated essential hypertension; we matched the patients for age, sex, body surface area, and blood pressure (BP) levels. Left ventricular hypertrophy (LVH) was identified by M-mode echocardiography in six patients with pheochromocytoma and in four with essential hypertension. Among both groups there were no differences in cardiac structure, no correlation between left ventricular mass and BP, no significant differences in mitral E-F slope, no correlation between either plasma norepinephrine or plasma epinephrine levels, and no differences in the left ventricular structural indices measured. In the pheochromocytoma group, left ventricular end systolic stress and end systolic diameter were significantly lower and left ventricular percent fractional shortening was higher. Plasma norepinephrine levels were higher in the pheochromocytoma group, but did not differ among patients of that group with and without LVH. We conclude that in both pheochromocytoma and essential hypertension, only a subset of patients develop evidence of LVH, and that in pheochromocytoma, the elevation of circulating plasma catecholamines is not necessarily associated with LVH. These results indicate that factors other than catecholamines and BP determine the development of LVH in pheochromocytoma.

Adolescent↗
PubMed1990

Atrial natriuretic factor in patients with right ventricular infarction.

To determine the possible role of atrial natriuretic factor in right ventricular infarction, serial measurements of this hormone were performed in 21 patients with acute inferior myocardial infarction. All patients underwent enzymatic, electrocardiographic, echocardiographic and coronary arteriographic studies. Ten patients also had right heart hemodynamic measurements. Eight patients had evidence of an associated right ventricular infarction (Group I) and 13 patients did not (Group II). Enzymatically estimated infarct size, presence of left heart failure and arrhythmias were similar in both groups. Mean arterial pressure in Group I (72.1 +/- 4.4 mm Hg) was significantly lower (p = 0.02) than in Group II (89.5 +/- 4.6 mm Hg). Seven (88%) of the eight patients in Group I had elevated right atrial pressures and a higher incidence than Group II of prolonged hypotension (75%) and right ventricular dysfunction (75%) clinically and by echocardiography. Plasma atrial natriuretic factor levels (mean values +/- SEM in pg/ml) for days 1, 2, 3 and 7 after infarction were, respectively: 152 +/- 30, 165 +/- 48, 199 +/- 27 and 189 +/- 31 for Group I versus 55 +/- 9, 55 +/- 11, 61 +/- 13 and 77 +/- 20 for Group II. The difference between groups was significant for days 1 (p less than 0.05), 3 and 7 (p less than 0.01) and not significant for day 2 (p = 0.07). These findings show that atrial natriuretic factor elevation is part of the neurohumoral response to right ventricular infarction and are consistent with the hypothesis that atrial natriuretic factor may play a pathophysiologic role in the right ventricular infarct syndrome.

Adult↗
PubMed1990

The haemodynamic effects of correction of anaemia in haemodialysis patients using recombinant human erythropoietin.

STUDY OBJECTIVE: To evaluate the acute and long-term haemodynamic response to recombinant human erythropoietin (rHuEpo) correction of chronic anaemia in haemodialysis-supported patients. DESIGN: Prospective analysis of randomly chosen patients undergoing the multicentre phase III clinical recombinant erythropoietin trial. SETTING: Chronic haemodialysis patients supported in one of two dialysis centres of a large urban tertiary referral centre. PATIENTS: Thirteen of the 59 patients who met the criterion for participation in the multicentre clinical phase III trial of recombinant erythropoietin were randomly chosen. Mean age (42.6 years), and time on dialysis (3.4 years) was representative of the study population. Ten patients were receiving antihypertensive therapy, which remained unchanged throughout the study. INTERVENTIONS: Haemodynamic testing was done in a fasting state, in the supine position, utilising radionuclide angiocardiography. Plasma volume was determined by 125I-labelled serum albumin. Echocardiographic and hormonal evaluations were also performed at each haemodynamic evaluation. All testing was done immediately prior to first dose of drug, upon reaching target haematocrit, and at 6 months and 1 year of continued non-anaemia. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure did not seem to change at any of the study periods, while total peripheral resistance did drop at target (34 +/- 2.5 vs 27.2 +/- 3.2 microns2, P = 0.05). Cardiac output (5.6 +/- 0.5 vs 7.6 +/- 0.8 l/min, P = 0.005) and stroke volume (77 +/- 9.6 vs 116 +/- 15.4 ml, P = 0.005) also rose at this same period but returned to baseline during later periods. Ejection fraction increased over baseline at both target and 1 year study points (50 +/- 2.7 vs 57.7 +/- 3 vs 63 +/- 4.3, P = 0.05) while the haematocrit was increased at target (21.8 +/- 0.9 vs 35.6 +/- 1.0, P less than 0.0005), and maintained at this new level throughout the study. Total blood volume (118 +/- 6.7 vs 100.4 +/- 8.1 ml/cm, P less than 0.05) and plasma volume (150 +/- 8.2 vs 108.5 +/- 9.4 ml/cm, P less than 0.001) decreased at 1 year. CONCLUSION: Recombinant human erythropoietin is effective in correcting the anaemia of chronic renal failure. Any haemodynamic changes which may be induced seem to occur early in the course of therapy, are different from those changes induced by blood transfusions, and tend to return to baseline with continued treatment.

Adolescent↗
PubMed1990

Impaired aldosterone production by long-term infusion of atrial natriuretic factor.

This study assessed the effect of chronic infusions of atrial natriuretic factor (ANF) on in vivo and in vitro production of aldosterone. Vehicle (saline) or rat ANF-(99-126) was intravenously infused at 100 ng.kg-1.h-1 for 5 consecutive days into male New Zealand White rabbits. At 5 days plasma ANF was 18 +/- 4.1 pg/ml in vehicle-infused and 48.5 +/- 9.0 in ANF-infused rabbits (P less than 0.01). Plasma renin activity was significantly less in ANF-infused rabbits (2.99 +/- 0.35 vs. 0.77 +/- 0.12 ng.ml-1.h-1, P less than 0.01); however no differences were observed in the basal plasma concentrations of aldosterone, corticosterone, potassium, or hematocrit. In in vivo studies, chronically administered ANF attenuated plasma aldosterone, but not pressor, responses to acutely infused angiotensin II given at doses of 4, 16, and 64 ng.kg-1.min-1 for 20 min each. In in vitro experiments, collagenase-dispersed adrenal capsular cells from ANF-infused rabbits exhibited significantly reduced maximal responses to adrenocorticotropic hormone, angiotensin II, and potassium. These results suggest that chronic small increases in circulating ANF can blunt selectively adrenocortical responses to aldosterone secretagogues without affecting pressor responses to angiotensin II.

Adrenal Medulla↗
PubMed1990

Feminizing adrenocortical tumor: steroid hormone response to ketoconazole.

A 58-yr-old man presented with gynecomastia and elevated serum estrogens. The diagnosis of an estrogen-secreting adrenal tumor was made based upon the finding of a 4-cm left adrenal mass, elevated levels of estradiol in peripheral and left adrenal venous blood, and increased urinary 17-ketosteroids. In addition to marked elevations in estradiol and 17-ketosteroids there was an increased baseline level of 11-deoxycorticosterone and a slightly decreased level of 18-hydroxycorticosterone, suggesting the possibility of impaired P450c11 activity. The effect of ketoconazole administration (600 mg/day) for 4 weeks was studied. Urinary free cortisol and 17-ketosteroid excretion and serum testosterone levels fell acutely (1 week). Serum estradiol levels decreased gradually over the 4-week course. Plasma aldosterone levels were essentially unaltered and 18-hydroxcorticosterone levels fell gradually, but there were marked increases in 11-deoxycorticosterone and corticosterone. Coincident with the increase in 11-deoxycorticosterone there was an increase in blood pressure and a transient fall in serum potassium. We conclude that ketoconazole administration may result in a hypermineralocorticoid state. Therefore, the usefulness of ketoconazole therapy for steroid hormone-producing neoplasms will depend upon the individual tumor's steroidogenic profile.

17-Ketosteroids↗
PubMed1990

Perioperative management of 63 patients with pheochromocytoma.

During a 10-year period, 60 patients with confirmed diagnoses of pheochromocytoma underwent a total of 63 surgical procedure. To control extreme blood pressure elevations, 6 patients received phenoxybenzamine preoperatively and 28 patients received prazosin. The remaining 29 patients received neither drug. Intravenous sodium nitroprusside and nitroglycerin, alone or in combination, were used in all but 10 patients to control intraoperative hypertensive episodes. One patient died after surgery due to pre-existing intracranial malignant tumor. All other patients were discharged from the hospital with no clinical evidence of stroke or myocardial infarction. We conclude that pheochromocytoma patients can undergo successful surgery without preoperative profound and long-lasting alpha adrenergic blockade.

Adolescent↗