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Biomedical subjects

M Mannelli

Publications and source records attributed to M Mannelli.

At least 55 records · Page 3Linked to original sources
PubMed1995

[Diagnostic problems in pheochromocytoma].

Pheochromocytoma is mainly characterized by a great deal of variability in its biological activity and in its clinical manifestations. This special feature has always to be taken into account in any diagnostic procedure. The tumor is generally suspected on clinical ground for the presence of paroxysmal hypertension but this sign is largely aspecific and often absent. The diagnosis of pheochromocytoma has to be based on laboratory tests demonstrating an excess and/or a disregulation in catecholamine (CA) secretion. CA or CA metabolites can be measured in urine or blood. Whatever the sample measured, it is important to correlate its result with the clinical picture found during its collection. Basal plasma CA concentrations are often raised also during periods of normotension but their accuracy is the highest in samples drawn during a hypertensive crisis. When basal measurements are insufficient for a final diagnosis, inhibitory (clonidine) or stimulatory (glucagon) tests can be performed. Clonidine test is recommended in patients showing slight increases in basal plasma CA. Glucagon stimulation test should be performed only in normotensive patients with an incidental adrenal mass, patients with sporadic hypertensive crises or members of families affected by MEN II. Localization procedures are mainly based on CT (or MRI) and on scintigraphy with I131-MIBG. CT possesses high sensitivity (about 96%) while I131-MIBG scintigraphy possesses a very high specificity (about 97%). Therefore, both the procedures should be performed before surgery. Rarely, it is also necessary to perform catheterization of the venous tree and plasma sampling for CA measurement to localize the tumor through the discovery of a secretory gradient.

3-Iodobenzylguanidine↗
PubMed1994

A further case of giant intrasellar carotid aneurysm mimicking a pituitary adenoma: the relevance of a multivariate approach in differential diagnosis.

We describe a 53 year old woman who progressively showed a left extrinsic oculomotor paresis, at first suggesting ocular myasthenia, which was ruled out by a negative Tensilon test. A CT scan of the brain revealed a pituitary mass consistent with an adenoma which was confirmed by endocrinological investigation and standard MRI. Carotid angiography, performed the day before the scheduled trans-sphenoidal surgery, clearly showed a giant intrasellar aneurysm of the left carotid syphon. An extra-intracranial by-pass with occlusion of the internal carotid artery was successfully executed.

Adenoma↗
PubMed1994

Bilateral massive adrenal hemorrhage due to sepsis: report of two cases.

Two cases (a 57-year-old man and an 18-year-old girl) of bilateral massive adrenal hemorrhage (BMAH) due to sepsis (Streptococcus pneumoniae and Neisseira meningitidis, respectively) are reported. At admission, the man presented with fever, severe hypotension, hyperazotemia, acidosis, normonatremia and hypocoagulability, while the girl with severe hypotension, fever, hyponatremia, and hypocoagulability. A diagnostic protocol based on a very quick method for cortisol measurement is proposed, in an attempt to reach an earlier diagnosis of BMAH during sepsis.

Adolescent↗
PubMed1994

Presence and distribution of endothelin-1 gene expression in human kidney.

To investigate the presence and the distribution of preproendothelin-1 (prepro-ET-1) mRNA in human kidney, eight human kidneys obtained at surgery from patients affected by localized renal tumors were studied. Northern blot analysis using a human prepro-ET-1 cDNA probe labeled with 32P showed the presence of a single band of approximately 2.3 kb that was present both in the renal cortex and medulla of all the kidneys studied. Densitometric analysis of hybridization signals demonstrated that prepro-ET-1 mRNA levels in the renal medulla were 2.2-fold higher than those in the renal cortex. The distribution of prepro-ET-1 mRNA in human kidney was investigated by in situ hybridization using a human prepro-ET-1 RNA probe labeled with 35S. The greatest density of prepro-ET-1 mRNA was observed in the renal medulla, where hybridization signal was demonstrated in vasa recta bundles and capillaries and in collecting ducts. By combining in situ hybridization with immunohistochemical detection of von Willebrand factor, we demonstrated that 93 +/- 2.5% of nontubular medullary cells containing prepro-ET-1 mRNA were endothelial cells. In the cortex, prepro-ET-1 mRNA was localized in the endothelial layer of arcuate and interlobular arteries and veins and in the endothelial cells of afferent arterioles. The results of the present study demonstrate that ET-1 gene expression is present in vascular and tubular structures of the human kidney. It is possible that ET-1 synthesized locally in the human kidney represents a local system affecting renal hemodynamics and functions through paracrine and/or autocrine actions on different renal structures.

Aged↗
PubMed1994

Adrenal medulla secretion in Cushing's syndrome.

To investigate whether chronic endogenous hypercortisolism might alter adrenomedullary phenylethanolamine N-methyltransferase activity, we measured epinephrine/norepinephrine (E/NE) ratios in the adrenal venous blood of 8 patients undergoing surgery for Cushing's syndrome and in 12 control subjects undergoing surgery for left kidney diseases. To investigate the adrenomedullary secretory activity in Cushing's syndrome, we measured basal E plasma levels in 24 patients and 32 age- and sex-matched normal control subjects, and we evaluated the adrenomedullary response to glucagon in 9 patients and in 22 age- and sex-matched normal subjects. Last, to clarify whether chronic endogenous hypercortisolism might modify E plasma levels through a modification of E metabolism, we measured the E MCR in four patients and four age-matched controls. Mean (+/- SEM) E/NE ratio in adrenal venous blood was similar in patients with Cushing's syndrome (4.61 +/- 0.78) and in the control group (4.71 +/- 0.74). Mean (+/- SEM) basal plasma E was significantly lower in patients with Cushing's syndrome (98.2 +/- 10.9 vs. 184 +/- 25.1 pmol/L, P < 0.01) than in the control group. Similarly, plasma NE also was reduced (0.75 +/- 0.09 vs. 1.10 +/- 0.07 nmol/L, P < 0.01). In patients with Cushing's syndrome the E response to glucagon was significantly reduced (P < 0.01). E MCR was almost identical in patients with Cushing's syndrome (1.48 +/- 0.10 L/min.m2) and in control subjects (1.51 +/- 0.10 L/min.m2). Our data demonstrate that: 1) chronic endogenous hypercortisolism is not able to change adrenomedullary phenylethanolamine N-methyltransferase activity and therefore the quality of adrenomedullary secretion; and 2) chronic endogenous hypercortisolism causes a decrease in basal and stimulated adrenomedullary activity without altering E MCR significantly. Therefore the adrenal medulla does not seem to play a pathogenetic role in the hypertension of Cushing's syndrome.

Adrenal Medulla↗
PubMed1994

Dopamine D2 receptor gene expression and binding sites in adrenal medulla and pheochromocytoma.

To determine whether dopamine D2 receptors are present in normal and neoplastic chromaffin tissues, 10 pheochromocytomas and 5 human adrenal glands were studied. Dopamine D2 receptor messenger ribonucleic acid corresponding to a single band of approximately 2.5 kilobases was detected in both pheochromocytoma and human adrenal gland by Northern blot analysis. D2 receptor messenger ribonucleic acid levels determined by dot blot analysis were 3.1-fold lower in human adrenal medullas than in pheochromocytomas (P < 0.001). Simultaneous Scatchard analysis of [3H]spiperone binding experiments demonstrated the presence of two different binding sites in membrane preparations from bovine adrenal medullas [R1: Kd = 0.14 nmol/L; binding capacity (Bmax) = 6.2 fmol/mg protein: R2: Kd = 16 nmol/L; Bmax = 223 fmol/mg protein]. Similarly, two binding sites were present in membrane preparations from pheochromocytomas (R1: Kd = 0.39 nmol/L; R2: Kd = 61 nmol/L]. Binding capacities were greatly variable among pheochromocytomas (R1: Bmax = 12.0-372.5 fmol/mg protein; R2: Bmax = 1,000-11,586 fmol/mg protein). The relative potencies of different compounds to displace [3H]spiperone were spiperone > domperidone > (+)-butaclamol > quinpirole > SCH 23390 in bovine adrenal medulla, and spiperone >> domperidone > quinpirole > (+)-butaclamol > SCH 23390 in pheochromocytoma. We conclude that dopamine D2 receptors are synthesized in human adrenal medulla and pheochromocytoma tissues.

Adrenal Gland Neoplasms↗
PubMed1994

Frequent RET protooncogene mutations in multiple endocrine neoplasia type 2A.

The occurrence of mutations in the RET protooncogene has been investigated in 12 multiple endocrine neoplasia type 2A families and 18 cases of sporadic thyroid medullary carcinomas and pheochromocytomas. Ten of 12 families showed single base substitutions in the RET protooncogene exons 10 and 11, coding for the extracellular domain of the protein. Tumor tissues from 2 multiple endocrine neoplasia type 2A patients were analyzed at the DNA and ribonucleic acid levels and revealed the same heterozygous mutations found in the peripheral blood lymphocytes. This demonstrates that both the normal and mutant alleles are expressed. No mutations in these exons were detected in the 18 cases of sporadic tumors investigated. These data provided further evidence that the mutated RET protooncogene acts in a dominant fashion and is responsible for the pathogenesis of this syndrome.

Adrenal Gland Neoplasms↗
PubMed1993

Renal effects of atrial natriuretic peptide during dopa-decarboxylase inhibition in patients with essential hypertension.

To assess whether intrarenal dopamine synthesis could contribute to the renal response to ANP in essential hypertension, the effects of alpha-human ANP infusion (50 ng.min-1.kg-1 b.w. for 30 min) on the urinary excretion of dopamine and sodium, urine flow rate and arterial pressure were evaluated in 7 patients with mild-moderate essential hypertension before (control period) and during DOPA-decarboxylase inhibition with carbidopa (carbidopa period). In the control period, urinary dopamine excretion was 400 pg.min-1 in baseline conditions and 340 pg.min-1 during ANP infusion. Carbidopa significantly decreased urinary dopamine excretion both before (210 pg.min-1) and during ANP (99 pg.min-1). In contrast, carbidopa did not affect sodium excretion (control from 184 to 460 mu Eq.min-1; carbidopa period from 140 to 390 mu Eq.min-1) or urine flow rate (control from 5.35 to 11.21 ml.min-1; carbidopa period from 4.29 to 11.54 ml.min-1). Arterial pressure fell significantly during ANP infusion in both periods, and no significant difference was observed between the two study days, i.e. in the absence of and during carbidopa administration. We conclude that DOPA-decarboxylase inhibition does not influence the diuretic and natriuretic response to alpha-human ANP infusion in patients with essential hypertension.

Adult↗
PubMed1993

A nonsecreting pheochromocytoma presenting as an incidental adrenal mass. Report on a case.

A 25 year old women presented an incidental adrenal mass which was diagnosed to be a pheochromocytoma before surgery by means of a positive 131-I-MIBG scintigraphy. Urinary vanilmandelic acid resulted repeatedly normal as well as basal plasma norepinephrine (NE), epinephrine (E) and dopamine (DA). Urinary homovannilic acid resulted in the normal range. Stimulation tests with iv glucagone, tyramine and metoclopramide evoked normal NE and E responses while a slight increase in plasma DA was observed after metoclopramide. Oral clonidine suppressed plasma catecholamines (CA) normally. Histologic and immunohistochemical studies confirmed that the tumor was a pheochromocytoma showing positivity for tyrosine hydroxylase but not for dopamine-beta-hydroxylase activity. This case is the first report on a completely asymptomatic pheochromocytoma presenting as an incidental adrenal mass which was investigated with repeated biochemical tests before surgery and demonstrates that, among the extremely variable functional attitudes of pheochromocytomas, a defect in CA synthesis and secretion is also to be included.

Adrenal Gland Neoplasms↗
PubMed1990

Dopamine modulation of pathological human chromaffin tissue.

To evaluate the presence of dopamine-2(DA2) binding sites in pheochromocytoma tissue, we performed binding studies and light microscopy autoradiography on sections of 7 different tumors. 3-H-Spiroperidol, a DA2 ligand, bound specifically to tumor sections with a (mean +/- SD) Kd value of 1.93 +/- 0.62 nmol/L. Binding site density (Bmax) was 29.16 +/- 2.33 fmol/mg tissue. Light microscopy autoradiography showed a nonhomogenous localization of silver grains within chromaffin cells. The specific binding was about 50% of total. To investigate whether DA2 binding sites found on pheochromocytoma cells might modulate catecholamine (CA) release, we studied the effects of oral bromocriptine (2.5 mg) on circulating CA of 5 patients with pheochromocytoma. In these patients bromocriptine caused a decrease in blood pressure (P less than .05) but no significant change in plasma CA. Our study shows the presence of DA2 binding sites on tumoral chromaffin tissue. As bromocriptine, a DA2 receptor agonist, was not able to modify tumor CA secretion, the functional role, if any, played by these binding sites on tumor secretion is still to be clarified.

Adrenal Gland Neoplasms↗
PubMed1990

Dopaminergic modulation of human adrenal medulla: indirect evidence for the involvement of DA-2 receptors located on the chromaffin cells.

1. Pharmacological blockade of DA-2 receptors causes a significantly higher epinephrine (E) response to physical exercise in normal man. 2. The present study was undertaken to evaluate whether dopaminergic modulation of E secretion is present also for a stimulus such as glucagon which acts directly on chromaffin cells. 3. Seven normal males were studied in a single blind randomized manner on two separate occasions, after pre-treatment with placebo or domperidone (DMP; 20 mg orally). Plasma E and norepinephrine, plasma prolactin, heart rate and blood pressure were measured on two separate occasions (placebo vs DMP) before and after a glucagon (1 mg i.v.) stimulation test. 4. Glucagon caused an increase in plasma E either after placebo (P = 0.043) or after domperidone (P = 0.012). DMP administration caused a significant increase in plasma E (P = 0.0008). Absolute increase in plasma E after glucagon was significantly higher after DMP than after placebo (P = 0.030). 5. As the dopaminergic modulation of human adrenal medulla is confirmed also for a stimulus acting directly on chromaffin cells, the results of the present study suggest that the DA-2 receptors responsible for the modulation are located on medullary cells.

Adrenal Medulla↗
PubMed1990

Catecholamines and blood pressure regulation.

Catecholamines (CAs) play a central role in the regulation of blood pressure. Sympathetic adrenal effects are ultimately elicited by the neurotransmitter norepinephrine and the hormone epinephrine. Their release is under the control of higher centers and is finely modulated by several factors such as presynaptic receptors. Recent evidences suggest that also the peripheral dopaminergic system can participate in blood pressure regulation intervening in the blood flow regulation of some regions, and in sodium-water balance. The measurement of CAs in biological fluids has greatly enhanced our knowledge on the mechanisms regulating blood pressure and is widely applied in cardiovascular research. Clinical applications of CA measurement are still limited to the diagnosis of pheochromocytoma and to the differential diagnosis of hypotensive syndromes.

Adrenal Gland Neoplasms↗
PubMed1989

Regional differences of adenylate cyclase stimulation by calcitonin and calcitonin gene-related peptide in the human kidney.

Calcitonin (CT) gene-related peptide (CGRP)-like immunoreactivity was detected in both the cortex and medullo-papillary portion of human kidneys. The two forms of human CGRP as well as rat CGRP were capable of stimulating renal cortical adenylate cyclase activity in a concentration-related manner, with a half-maximally effective concentration (EC50) similar to that of human CT and approximately 100-1000 times higher than that of salmon CT. However, in the medullo-papillary portion, in which both salmon CT and human CT were inactive, the two forms of human and rat CGRP increased adenylate cyclase activity by 100%, with EC50 values ranging from 36 nmol/L to 1 mumol/L. In cortical membrane preparations the effect of CGRP was additive to that of salmon CT. We concluded that regional differences exist in the effect of CT and CGRP in human renal tissue and that in the medullo-papillary portion and possibly in the cortex, CGRP stimulates adenylate cyclase activity through a CT-independent mechanism.

Adenylyl Cyclases↗
PubMed1988

Presence of dopamine-dependent adenylate cyclase activity in human renal cortex.

The effects of dopamine (DA) and of two selective DA DA1 agonists (SKF 38393 and SKF 82526) on adenylate cyclase activity were studied with human kidney cortex membrane preparations. DA elicited a dose-related stimulation of adenylate cyclase activity with an EC50 of 60 microM. The selective DA DA1 antagonist SCH 23390 behaved as a competitive antagonist, shifting the dose-response curve to the right. The non-selective beta-adrenoceptor antagonist (-)-propranolol did not affect the EC50 of the dose-response curve to DA but attenuated the maximal stimulatory effect of DA at concentrations higher than 100 microM. (+)-Sulpiride inhibited DA-induced adenylate cyclase stimulation in a dose-dependent manner with an IC50 of 4.6 X 10(-8) M but (-)-sulpiride was without effect. Both SKF 38393 and SKF 82526 stimulated the adenylate cyclase activity of human kidney cortex; this effect was completely antagonized by SCH 23390. Our results, demonstrating the presence of DA-sensitive adenylate cyclase activity, strongly suggest the presence of a DA receptor of the DA1 subtype in human kidney cortex.

Adenylyl Cyclases↗