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Biomedical subjects

M Boscaro

Publications and source records attributed to M Boscaro.

At least 145 records · Page 8Linked to original sources

In vitro studies on the effects of ranitidine on isolated anterior pituitary and adrenal cells.

The effects of ranitidine on anterior pituitary and adrenal function have been studied using isolated perfused rat anterior pituitary and zona glomerulosa cells. Ranitidine did not have pituitary hormone releasing activity with respect to LH, TSH, GH and ACTH. It also did not alter prolactin secretion in experiments designed to test whether it acted as a dopamine agonist or antagonist. In the adrenal cell studies ranitidine infusion stimulated basal aldosterone secretion and inhibited the release of aldosterone in response to angiotensin II, but not to ACTH. These experiments suggest that ranitidine is unlikely to alter pituitary hormone secretion by a direct action on the pituitary. The drug, however, can affect aldosterone secretion in vitro and further in vivo studies are required to elucidate the significance of this.

Adrenal Cortex↗

In vivo and in vitro studies on the effect of metoclopramide on aldosterone secretion.

Metoclopramide, a dopamine antagonist drug, elevated plasma aldosterone and prolactin levels without significantly affecting plasma renin activity, ACTH or potassium. Studies with isolated perfused rat zona glomerulosa cells showed that metoclopramide could directly stimulate aldosterone release and that this action was blocked by dopamine. These results suggest that dopamine may play an important inhibitory role in the control of aldosterone secretion.

Adrenal Glands↗

[Diaxozide-induced acute stimulation of plasma renin activity in renal veins for diagnosis and prognosis in hypertensive patients (author's transl)].

Vena cava and renal veins PRA were measured and their ratios calculated (Ra/Rc and Rc/P) in 15 hypertensive patients before and after diazoside infusion (300 mg i.v.). Among the 4 patients with unilateral renal artery stenosis, 3 had both ratios significant in basal conditions. After diazoxide infusion, the ratios became significant in the 4th case, successfully operated. Surgery induced normalization of blood pressure also in 2 of 3 cases affected by renoparenchimal alterations: of these patients 1 had ratios significant in basal conditions and both after diazoxide. One patient had unilateral renal artery stenosis and controlateral small kidney: his ratios was significant in favour of small kidney both before and after diaxozide infusion. The correction of renal artery stenosis gave no results in blood pressure. In patients with essential hypertension the PRA values in renal veins were not significantly different either before and after diazoxide. In conclusion the acute diazoxide stimulation seems to improve the prognostic value of renal veins PRA and their ratios for the detection of surgically curable forms of renal hypertension.

Adolescent↗

Plasma renin activity and urinary aldosterone in Cushing's syndrome.

The renin-angiotensin-aldosterone system has been evaluated in 19 patients with Cushing's syndrome due to bilateral adrenal hyperplasia and in 2 patients with unilateral adenoma. In the first group urinary aldosterone was within the normal limits with a mean of 8.3 +/- 1.86 microgram/24 h. Aldosterone excretion did not change significantly after furosemide administration, ACTH infusion or dexamethasone. Upright PRA was suppressed in 9/16 patients with a mean of 4.9 +/- 1.85 ng/ml/3 h and showed only a slight response to furosemide. Dexamethasone alone did not produce any change. Both aldosterone and PRA were to some extent stimulated by an association of dexamethasone and furosemide. In the 2 patients with adenoma, aldosterone excretion was also normal, but PRA was very elevated. From our data it is concluded that in Cushing's syndrome due to bilateral hyperplasia, PRA and aldosterone excretion are partially suppressed. From our results on plasma deoxycorticosterone and corticosterone concentration it seems unlikely that these mineralocorticoids are the major cause of this phenomenon. However, it may not be excluded that other yet unidentified hormones could play some role in the pathogenesis of hypertension and renin suppression in Cushing's syndrome.

Adolescent↗

[Pheochromocytoma. Diagnostic aspects and surgical treatment. Apropos of 20 operated cases].

Reference is made to 20 cases of pheochromocytoma operated at the surgical clinic of the University of Padua since 1963. Stress is laid on the importance of modern angiographic techniques in diagnosis and their attendant risks and the main aspects of surgical management are examined. The results show that success depends on careful preoperative localisation, choice of a suitable approach route, and correct technique coupled with suitable intraoperative management.

Abdominal Neoplasms↗

[Effect of diazoxide on blood pressure, PRA and plasma aldosterone in hypertensive patients (author's transl)].

Intravenous diazoxide (300 mg) was administered to 29 hypertensive patients previously classified in subgroups according to their plasma renin and urinary aldosterone levels. The blood pressure was measured before and periodically after injection and plasma renin activity (PRA) and plasma aldosterone before and after 2 hours. The mean systolic and diastolic blood pressure fell notably from 193/118 to 155 93 mmHg; whereas PRA increased from 7.51 to 13.21 ng/ml/3 hrs and plasma aldosterone did not change significantly (71.3 and 102.8 ng%). Examining the individual sub-groups, a significant decrease in blood pressure was observed in 15 patients with low, posture unresponsive PRA, both in subjects with normal urinary aldosterone and those with surgically proven primary aldosteronism. In the former only the mean PRA showed a slight but sigificant increase, while in the latter the changes for both PRA and aldosterone were not significant. In the subgroups of patients with normal renin and urinary aldosterone the arterial pressure also significantly and promptly decreased. However, in this group the mean PRA substantially increased whereas the plasma aldosterone levels remained constant. The same blood pressure decline was observed in those patients with high PRA and aldosterone, including 1 case of pheocromocytoma. The mean PRA showed a further modest increase while the plasma aldosterone did not change significantly. These results indicate that the antihypertensive action of diazoxide is similar in the different types of hypertension (volume, vasoconstrictor or mixed form according to Laragh's classification), being independent of the basal plasma renin and aldosterone levels. Furthermore, the response of the blood pressure to diazoxide is not related in any way to the induced changes in PRA and plasma aldosterone values.

Adrenal Gland Neoplasms↗

[Indications for study of adrenal function by measurement of the cortisol secretion rate].

Results of routine methods for measurements of plasma cortisol and his urinary metabolites have been comparated with those of cortisol secretion rate (CSR) measured by simple isotopic dilution; the latter appears for his specify and precision, to be the most suitable for an exact evaluation of cortisol production by the adrenals. In normal subjects CSR resulted slightly lower than those reported in the literature; in obese subjects CSR was slightly higher than in normals, also when it was related to the urinary creatinine. In the patients with Cushing's syndrome, CSR was considerably higher, with no overlap with the obese subjects. The CSR was also useful in showing values lower than normal, in hypopituitarism, and in confirming hormone abnormal findings in thyroid diseases.

Adolescent↗

Role of bilateral adrenalectomy in Cushing's disease.

Of 206 patients with Cushing's syndrome observed from 1975 through 1991, 144 (69.9%) had pituitary-dependent Cushing's disease. Of the 110 patients who underwent pituitary surgery, 31 (28%) developed an early recurrence and 23 patients (20%) had a late relapse 1 to 5 years after primary pituitary exploration. We performed a one- or two-step total bilateral adrenalectomy in 43 patients-9 men and 34 (79.4%) women, with an average age of 47.5 years (range 13-58 years). Thirty-three of these patients had already been treated by previous transsphenoidal surgery or alternatively by external pituitary irradiation over a period of 1 to 10 years prior to adrenal surgery. Thirty-one patients underwent adrenalectomy by a double lumbar access or left lumbar and right subcostal incisions. In our series of 55 operations, perioperative complications included two splenectomies and two hemorrhages (7.3%). The early mortality rate was 3.6% (two patients). Minor complications consisted of wound infection (13.5%), bronchopneumonia or pneumothorax (four cases) with a 7- to 12-day longer hospital stay. Nelson syndrome occurred in 6 of 41 patients (14.6%). We therefore believe that bilateral adrenalectomy does play a major role in the treatment of patients with pituitary-dependent Cushing's disease unsuccessfully managed by transphenoidal surgery. It represents the definitive therapy for those patients in whom hypophysectomy was not able to provide satisfactory control of the disease.

Adolescent↗

Effects of raloxifene on body fat distribution and lipid profile in healthy post-menopausal women.

The aim of our prospective, randomised, controlled and open-label clinical study was to evaluate in healthy post-menopausal women the effects of raloxifene (RLX) on body fat distribution and lipids, and the correlations between these parameters. The fat distribution, by dual energy X-ray absorptiometry, and lipids were evaluated at baseline and after 1 yr in 50 post-menopausal women: 25 were treated with RLX 60 mg/die, while 25 served as control group (CG). After 1 yr, we observed in RLX-users a slight reduction of fat mass in trunk and central region and an increase in legs and, in relation to CG, significantly lower values of adiposity in trunk and abdominal region (p < 0.05). At the same time, HDL-cholesterol (HDL-C) and apolipoprotein A1 (ApoA1) were significantly increased in relation to baseline values and CG (p < 0.05) and apolipoprotein B (ApoB), total cholesterol/HDL-C, LDL cholesterol/ HDL-C, and ApoB/ApoA1 ratios significantly decreased compared to baseline values and CG (p < 0.05). No correlation was underlined among lipids and regional fat distribution. These results highlight the positive effect of RLX on lipids and suggest, for the first time, that RLX promotes the shift from android to gynoid fat distribution, and prevents the uptrend of abdominal adiposity and body weight compared with untreated women.

Aged↗

Plasma renin activity and urinary aldosterone in acromegaly.

The behaviour of the renin-angiotensin-aldosterone system was evaluated in 16 acromegalic patients, of whom 7 were hypertensive. The patients were studied in basal conditions, after suppression with 9alpha-fluorohydrocortisone, and after stimulation with furosemide. Baseline and after furosemide PRA were significantly lower in acromegalic hypertensive patients than in the normotensive group. Mean urinary aldosterone excretion was found at the upper limits of the normal range; it was occasionally elevated, but the values were not satistically different in the two groups. There was a suppression after 9 alpha fluorohydrocortisone in both groups, though it did not reached the 50%. These data show that there is a disorder of the renin-angiotensin-aldosterone system in acromegalic subjects. This defective regulation is sometimes similar to that present in primary aldosteronism. In fact in two patients a typical phlebographic and scintigraphic picture of primary aldosteronism has been found; surgery, performed in both patients, revealed a large cortical adenoma in one case and a macronodular hyperplasia in the second case. However, the relationship between this adrenal abnormalities and hypertension in acromegaly are not yet completely clarified.

Acromegaly↗

Inhibitory effect of somatostatin on the aldosterone response to angiotensin II: in vitro studies.

It has been demonstrated that somatostatin (SRIF) can suppress hypophyseal and extrahypophyseal hormones; moreover, many studies have shown that SRIF inhibits frusemide-induced hyperreninemia in normal man, and renin and aldosterone in renovascular hypertension, possibly through a beta-adrenergic block. To further investigate the possible aldosterone-inhibiting effect of somatostatin, we have carried out in vitro studies using isolated perfused rat zona glomerulosa cells suspended in Bio-gel. Paired columns were set up and the cells stimulated using either angiotensin II, ACTH, serotonin or potassium. One column was perfused with somatostatin (3-4 ng/ml) and the other was used as a control. Aldosterone was measured by highly specific direct radioimmunoassay. Somatostatin significantly blocked the aldosterone response to angiotensin II but not to ACTH, serotonin or potassium. The inhibitory effect of somatostatin persisted as long as it was added to the medium; the aldosterone response to angiotensin II was progressively restored after discontinuation of the SRIF infusion. From these data it might be suggested that the inhibitory effect of somatostatin on aldosterone production is not cAMP-dependent, since ACTH maintains its stimulatory capacity. The recent demonstration of the presence of specific somatostatin receptors on the rat adrenal cells suggests that its inhibitory effect could be mediated by the second messenger system rather that the interaction with angiotensin II receptors.

Adrenal Glands↗

Paclitaxel is an effective antiproliferative agent on the human NCI-H295 adrenocortical carcinoma cell line.

In view of a potential clinical use, we assessed the antiproliferative effect of paclitaxel on the human steroid-secreting NCI-H295 adrenocarcinoma cell line. By MTT, paclitaxel induced a dose-dependent inhibition of cell proliferation, with IC50 lower than blood levels of the drug achieved in patients treated for other malignancies. Cell exposure to paclitaxel for 24 h at the different IC50S produced a dose-responsive increase in DNA fragmentation, morphologically confirmed by electron microscopy. A time-dependent decrease in aldosterone, cortisol and testosterone was observed. Paclitaxel is an effective antiproliferative agent in this human adrenocortical carcinoma cell line. Apoptosis induced by the drug in involved in neoplastic cell death. A potential role of the drug in the treatment of patients with adrenocortical cancer could be considered.

Adrenal Cortex Neoplasms↗

A clinical index for rating severity in Cushing's syndrome.

BACKGROUND: In assessing the clinical response to medical and/or surgical treatments in patients with established Cushing's syndrome, the need for an instrument that could measure the magnitude of changes in the most common symptoms was felt. We therefore tested the usefulness of a simple clinical index, the Cushing's syndrome severity index (CSI), based on clinimetric principles. Eight clinical features were selected. Each one was graded on an ordinal 3-point scale (0-2) with specification of anchor points based on severity. The total score ranged from 0 to 16. METHODS: Interrater agreement, construct validity and concurrent validity of the index were evaluated. Fourteen patients with Cushing's syndrome were evaluated independently by 2 endocrinologists before and after successful treatment. The CSI and two global scales of illness severity were administered. Urinary cortisol measurements were also performed. RESULTS: The intraclass correlation coefficient of the CSI was 0.95 before treatment and 0.87 after treatment. The CSI significantly discriminated (p<0.001) the effects of treatment and paralleled the changes in urinary cortisol. There were significant correlations between CSI and global scales of illness severity and change after treatment. CONCLUSION: The results indicate that the CSI is a valid and reliable clinimetric method to evaluate severity in Cushing's syndrome. It may provide a tool for better assessing the complex array of signs and symptoms in this condition. The index is suitable for descriptive studies, outcome investigations and treatment trials.

Adolescent↗