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Biomedical subjects

L Fedeli

Publications and source records attributed to L Fedeli.

33 records · Page 2Linked to original sources

Efficacy of two different doses of muzolimine in the treatment of mild hypertension.

UNLABELLED: A report is given on the effects of oral therapy with muzolimine (M) in patients with mild hypertension. SUBJECTS AND METHOD: 21 untreated patients, aged 35 to 69 (mean 53.1 yrs) with orthostatic diastolic BP between 100 and 115 mmHg were randomly assigned to either group A (10 mg M/day) or group B (20 mg M/day) in a single blind study for a period of two weeks. Clinostatic and orthostatic systolic and diastolic BP and heart rate were recorded at weekly intervals. PRA, aldosteronemia, ECG and blood chemistry were analyzed at the beginning and at the end of the study. Student's t-test was used for the statistical evaluation and p values below 0.05 were considered significant. RESULTS: Both clinostatic and orthostatic diastolic BP were significantly reduced in group A whereas only orthostatic diastolic BP was decreased in group B (Fig. 1). PRA and aldosteronemia values and blood chemistry showed no statistically significant changes. No side effects were noted. We conclude that 10 mg/day of muzolimine is more effective than 20 mg/day in reducing orthostatic diastolic BP (A vs. B p less than 0.02). Although these results are only preliminary data and further investigations are required, they suggest that muzolimine may be safely used, in combination with other antihypertensive agents, particularly in cases of renal failure.

Adult↗

Does the hypothalamic tyrosine-hydroxylase inhibition mediate the positive feedback of progesterone on gonadotropin release in women?

Neuropharmacological studies suggest a common inhibitory role for the hypothalamic dopaminergic pathway on gonadotropin and prolactin pituitary release, in humans. As a consequence, it has been hypothesized that the inhibition of hypothalamic tyrosine-hydroxylase and the subsequent fall in dopamine synthesis is involved in the positive feedback of progesterone on LH and PRL pituitary release in estrogen-primed hypogonadal women. The aim of our study was to verify whether an inhibition of tyrosine-hydroxylase may really account for the progesterone action on gonadotropin and prolactin secretion. For this purpose, we compared the effect of a specific tyrosine-hydroxylase inhibitor (alpha-methyl-p-tyrosine, AMPT) with the effect of progesterone on gonadotropin and prolactin release in estrogen-primed postmenopausal women. Progesterone induced a marked release of LH (delta: 129.7 +/- 16.5 mlU/ml, mean +/- SE) and a slight increase in FSH (delta: 39.4 +/- 11.6 mlU/ml) and PRL (delta: 15.3 +/- 2.8 ng/ml) serum levels. Acute or two-day administration of AMPT was followed by a marked rise in PRL serum levels (delta: 82.9 +/- 13.8 and 88.3 +/- 8.2 ng/ml, respectively) while there were no significant increases in serum LH (delta: 5.4 +/- 2.6 and 3.3 +/- 4.6 mlU/ml) and FSH (delta: 3.4 +/- 0.9 and -0.4 +/- 2.9) concentrations. The ineffectiveness of a specific tyrosine-hydroxylase inhibitor in simulating the progesterone effect on gonadotropin secretion seems to negate the hypothesis that a reduction in hypothalamic dopaminergic activity mediates the positive feedback of progesterone on gonadotropin release.

Aged↗

Catecholamines and pituitary function. 2. Prolactin response to different dopamine doses in normal cycling women and patients with prolactin-secreting pituitary tumors, both before and after endogenous catecholamine synthesis inhibition.

The inhibitory effect of various doses of dopamine on serum PRL levels was assessed in both normal cycling women and patients with tumoral hyperprolactinemia before and after endogenous catecholamine synthesis inhibition by alpha-methyl-p-tyrosine, a strong and specific tyrosine-hydroxylase inhibitor. Dopamine infusion induced a significant decrease in the serum PRL levels in both normal cycling and hyperprolactinemic subjects. The mean percent inhibition of baseline PRL induced by the various dopamine infusion rates (0.1, 0.5, 1.0 and 2.0 micrograms/kg/min) was similar in regularly cycling women and in patients with tumoral hyperprolactinemia both before and after endogenous catecholamine synthesis inhibition by alpha-methyl-p-tyrosine. Alpha-methyl-p-tyrosine pretreatment significantly increased serum PRL concentrations in normal women and enhanced their responsiveness to the exogenously administered dopamine. Hyperprolactinemic patients, on the contrary, did not show any significant variation in either basal PRL release or the PRL sensitivity to dopamine infusion after endogenous catecholamine synthesis inhibition. These data indicate that reduced dopamine delivery to the adenomatous lactotroph, either due to a primary hypothalamic abnormality or to a deranged vascular pituitary arrangement, rather than a reduced PRL sensitivity to dopamine inhibition, is the main event accounting for PRL hypersecretion in women with PRL-secreting pituitary tumors.

Catecholamines↗

Catecholamines and pituitary function. I. Effects of catecholamine synthesis inhibition and subsequent catecholamine infusion on gonadotropin and prolactin serum levels in normal cycling women and in women with hyperprolactinemic amenorrhea.

To investigate the role of catecholamines in the control of gonadotropin and prolactin release, we examined the effects of a catecholamine synthesis inhibitor (alpha-methyl-p-tyrosine, AMPT) administration and those of dopamine (DA) or epinephrine (EPI) infusion after endogenous catecholamine synthesis inhibition, on FSH, LH and PRL serum levels, in regularly cycling women and in patients with hyperprolactinemic amenorrhea. AMPT administration was followed by a prompt increase in serum PRL in regularly cycling women, but not in women with hyperprolactinemia either due to a PRL-secreting pituitary microadenoma or 'idiopathic'. Gonadotropin serum levels did not show any significant variation after AMPT in both normal and hyperprolactinemic women. DA infusion after endogenous catecholamine synthesis inhibition by AMPT, induced an appreciable decline in PRL levels in both normal and hyperprolactinemic subjects. Although the net decrements were higher in the hyperprolactinemic group, the PRL fall was similar in the two groups when expressed as a percentage of preinfusion PRL concentrations. LH serum levels similarly fell during DA infusion in normal women and in hyperprolactinemic patients, while FSH concentrations did not show any significant change. EPI infusion after analogous AMPT pretreatment was followed by an evident decrease in serum PRL in both normal and hyperprolactinemic subjects. No significant changes in FSH and LH serum concentrations were observed during EPI administration. These data, while confirming the existence of a functional derangement in the neural inhibitory control of PRL secretion in hyperprolactinemia either due to a PRL-secreting pituitary microadenoma or so-called 'idiopathic', do not agree with the hypothesis that tubero-infundibular DA hyperactivity inhibits gonadotropin secretion in hyperprolactinemic patients. The inhibitory action of exogenously administered DA might represent rather a pharmacological effect than express a physiological inhibitory role of hypothalamic DA pathway on gonadotropin secretion in humans.

Adult↗

Catecholamines and pituitary function. III. Restoration of the prolactin response to thyrotropin-releasing hormone by low-dose dopamine infusion in women with pathological hyperprolactinemia.

Previous studies in Rhesus monkeys have demonstrated that a dopamine (DA) infusion rate of 0.1 microgram/kg X min induces peripheral DA levels similar to those measured in hypophysial stalk blood and normalizes serum prolactin (PRL) levels in stalk-transected animals. We therefore examined the effect of such DA infusion rate on basal and thyrotropin-releasing hormone (TRH)-stimulated PRL secretion in both normal cycling women and women with pathological hyperprolactinemia. 0.1 microgram/kg X min DA infusion fully normalized PRL serum levels in 8 normal cycling women whose endogenous catecholamine synthesis had been inhibited by alpha-methyl-p-tyrosine (AMPT) pretreatment. Furthermore, DA significantly reduced, but did not abolish, the rise in serum PRL concentrations induced by both acute 500 mg AMPT administration and 200 micrograms intravenous TRH injection in normal women. A significant reduction in serum PRL levels in response to 0.1 microgram/kg X min DA, similar to that observed in normal cycling women when expressed as a percentage of baseline PRL, was documented in 13 amenorrheic patients with TRH-unresponsive pathological hyperprolactinemia. However, a marked rise was observed in the serum PRL of the same patients when TRH was administered during the course of a 0.1-microgram/kg X min DA infusion. The PRL response to TRH was significantly higher during DA than in basal conditions in hyperprolactinemic patients, irrespective of whether this was expressed as an absolute increase (delta PRL 94.4 +/- 14.2 vs. 17.8 +/- 14.1 ng/ml, p less than 0.002) or a percent increase (delta% PRL 155.4 +/- 18.9 vs. 17.9 +/- 7.1, p less than 0.0005), and there was a significant linear correlation between the PRL decrements induced by DA and the subsequent PRL responses to TRH. These data would seem to show that the 0.1-microgram/kg X min DA infusion rate reduces basal PRL secretion and blunts, but does not abolish, the PRL response to both TRH and acute AMPT administration. The strong reduction in PRL secretion and the restoration of the PRL response to TRH by 0.1 microgram/kg X min DA infusion in high majority of hyperprolactinemic patients, seem to indicate that both PRL hypersecretion and abnormal PRL response to TRH in women with pathological hyperprolactinemia are due to a relative DA deficiency at the DA receptor site of the pituitary lactotrophs.

Adult↗

Testosterone-induced hyperprolactinaemia in a patient with a disturbance of hypothalamo-pituitary regulation.

A case of a patient with hypopituitarism due to a disturbance of hypothalamo-pituitary regulation is presented, who developed high-grade hyperprolactinaemia after the initiation of substitutive therapy with testosterone esthers. The increase in serum Prl was strictly related to testosterone aromatization to oestradiol, since anti-oestrogen compounds were effective in reducing (clomiphene) or abolishing (tamoxifen) the enhanced Prl secretion. The oestrogen effect in raising Prl release was not attributable to a reduction in the dopamine inhibition of Prl-secreting cells, as the dopamine-antagonist domperidone failed to increase Prl serum levels in the same patient. This suggests that, in man, the oestrogen effect in enhancing Prl release is mainly enacted directly on the pituitary lactotrophs rather than exerted through a reduction in the hypothalamic dopamine activity.

Adult↗

[Radioimmunoassay of high specificity for vincristine].

The authors set up a simple and fairly rapid radioimmunoassay for vincristine, that shows a good sensitivity, precision and specificity. In particular, the higher specificity in comparison with other similar dosage techniques is likely due to the marked specificity of the used anti-vincristine serum, which displays a low interference even by molecules with a vincristine-like structure. Therefore, the suggested radioimmunoassay technique seems quite suitable for studying vincristine pharmacokinetics and for monitoring blood levels of this alkaloid in treated patients.

Evaluation Studies as Topic↗

[Bronchial mucociliary function. A new diagnostic technic].

To study mucociliary clearance of central airways we used a recently described method consisting of the inhalation of 99mTc labeled autologous spherocytes aerosol. In 3 of 8 normal non smoking subjects, an abnormally low rate of m.c.c. was observed. The m.c.c. rate was also very low in 2 of 6 patients with bronchial cr. who never smoked. These observations provide considerable evidence that those non smoking subjects presenting with low mucociliary clearance may be regarded as "high risk subjects" for broncho-pulmonary diseases. The good central deposition pattern of the inhaled spherocytes may provide, in very ill patients, a non-invasive visualization of the central airways.

Adult↗

Progesterone positive feedback on gonadotropin release in estrogen-primed postmenopausal women: central nervous system and pituitary as possible sites of action.

To investigate the site and mode of action of progesterone in inducing gonadotropin release, the effects of catecholamine-depleting (methyldopa) or dopamine agonist (bromocriptine) drugs on progesterone positive feedback and the gonadotropin response to a centrally acting noradrenergic drug (clonidine) were evaluated in estrogen-primed postmenopausal women. Progesterone administration induced a significant rise in LH, FSH, and PRL serum levels in the control group. Bromocriptine administration was followed by a marked suppression of PRL release but did not modify the gonadotropin response to progesterone. Methyldopa pretreatment significantly reduced the progesterone-induced LH surge, while PRL release was unaffected. After estrogen priming, clonidine administration did not result in an increase in serum LH or FSH concentrations. The dissociated responses of LH and PRL in bromocriptine-pretreated subjects and the significant reduction of the LH rise after progesterone in methyldopa-pretreated women seem to invalidate the hypothesis that a fall in endogenous dopamine is responsible for progesterone positive feedback and suggest that neural noradrenergic mechanisms are involved in progesterone-induced gonadotropin release. The ineffectiveness of a centrally acting noradrenergic agonist in inducing gonadotropin rise provides indirect evidence that an increased pituitary responsiveness may also be involved in progesterone positive feedback.

Aged↗

Effect of estrogens and progesterone on gonadotropin and prolactin release in a patient with androgen insensitivity.

Response of serum levels of gonadotropins and prolactin to doses of estrogen and progesterone was measured in a patient with the complete form of androgen insensitivity, ie, testicular feminization. Before gonadectomy a single 2.5-mg dose of estradiol benzoate (E2B) produced a decrease in gonadotropin levels. Gonadectomy resulted in a rise of serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but had no effect on levels of prolactin. The following results were obtained after gonadectomy: During low-dosage therapy with ethinyl estradiol (EE) a single 2.5-mg dose of E2B produced a decrease in FSH and LH levels, no LH surge, and a small rise in prolactin levels. With a tenfold higher EE priming, the same dose of E2B provoked an LH surge; progesterone administration produced FSH, LH, and prolactin release. However, progesterone priming blocked the positive feedback of estradiol and enhanced its negative feedback. Pituitary sensitivity ot nonandrogenic steroids appears to be normal in cases of testicular feminization. Under this condition, after gonadectomy, the dynamics of gonadotropins and prolactin in response to estrogens or progesterone administration are similar to those in normal women and suggest that aromatization products of testosterone do not produce any irreversible effects on neuroendocrine differentiation of androgen-insensitive patients

Adult↗

[Visualization of carotid and femoral atherosclerotic lesions using autologous lipoprotein reinjection containing apo-B marked with 131I: preliminary data].

Atherosclerotic lesions can be detected by several methods, such as angiography, B-mode ultrasonography, computed tomography and magnetic resonance. Radioisotopic techniques, recently introduced by using radiolabelled platelets and LDL (low-density lipoproteins), can give more informations about the "metabolic activity" of atherosclerotic lesions. The aim of this study was to detect atherosclerotic lesions in 7 hyperlipemic patients using autologous apo-B containing lipoproteins labelled with 131I in order to evaluate different functional patterns of these lesions. Carotid and femoral accumulations of this radiocompound were detected in the majority of patients. The method appears promising for evaluating the "in vivo" relationships between lipoproteins, which are involved in the pathogenesis of atherosclerosis, and the vessel wall.

Adult↗