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Biomedical subjects

C Scaroni

Publications and source records attributed to C Scaroni.

At least 37 records · Page 2Linked to original sources

Low-dose ketoconazole treatment in hirsute women.

Ketoconazole is an orally active antimycotic agent and a potent inhibitor of gonadal and adrenal steroidogenesis. As inhibitor of steroid production, it has been employed in Cushing's syndrome, prostatic cancer and precocious puberty due to autonomous Leydig-cell hyperfunction. By virtue of its selective action on androgen synthesis at low doses by inhibition of C17-20 lyase, this drug could be of potential therapeutic utility in hirsutism. We evaluated the hormonal and clinical effects of a low-dose regimen (400 mg/day) for 3 months in 16 women with a spectrum of disorders from idiopathic hirsutism to polycystic ovary syndrome. Four of them completed 6-month treatment. At 3 months, DHEA-S decreased from 9.9 +/- 1.0 (mean +/- SE) to 6.9 +/- 1.0 mumol/L (p less than 0.01), androstenedione from 13.3 +/- 1.5 to 8.3 +/- 1.3 nmol/L (p less than 0.005), and testosterone from 4.2 +/- 0.4 to 3.1 +/- 0.4 nmol/L (p less than 0.05). No significant changes were observed in LH, FSH, prolactin and estradiol levels. In patients treated for 6 months, androgens were within normal limits at the end of the study. Eleven out of 16 women (about 70%) reported some improvement in their hirsutism. There was a significant decrease in Ferriman-Gallwey's score (p less than 0.001) and mean hair-shaft diameter (p less than 0.001). The patients treated for 6 months showed a further improvement. Pelvic ultrasonography, when repeated (n = 8), was either unchanged or improved. Side effects (polymenorrhea, gastrointestinal reaction, somnolence) were generally mild and transient. Of 20 women who entered the study the dropout rate was 20% (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

New aspects of mineralocorticoid hypertension.

Primary aldosteronism is the principal disorder of the zona glomerulosa, and a number of subsets have been identified: unilateral adenoma, bilateral micro- or macronodular hyperplasia (idiopathic aldosteronism), primary hyperplasia, and aldosterone-producing carcinoma, either adrenal or ectopic. The diagnostic criteria for a correct differential diagnosis of these subsets are now quite reliable, and our experience is presented in detail. Unfortunately, the pathogenesis of most of these forms is still poorly recognized and requires further investigation. An extreme sensitivity to angiotensin II is present in patients with idiopathic aldosteronism, and a role of adrenal renin is now being advocated. A peculiar form of hyperaldosteronism is the glucocorticoid-remediable subtype. An unusual sensitivity of aldosterone to ACTH is present in this form. The qualitative biochemical abnormality in this disorder consists of a marked overproduction of products of the cortisol C-18-oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, which are more abundant than aldosterone and 18-hydroxycorticosterone. A family with 3 affected sibs has been studied by our group. In other clinical situations, classical zona fasciculata mineralocorticoids (deoxycorticosterone [DOC], corticosterone, and their 18-hydroxy compounds) are secreted in excess. The hypertensive diseases of this zone are rare DOC-secreting tumors and two forms of congenital adrenal hyperplasia, the 11 beta-hydroxylase and 17 alpha-hydroxylase deficiency syndromes, which are identified by the presence of hypokalemia and suppressed renin activity. DOC is the only mineralocorticoid hormone (MCH) oversecreted in the 11-hydroxylase deficiency syndromes, while all ACTH-dependent MCH levels are very high in the 17-hydroxylase deficiency syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Single-dose pharmacokinetics of flurbiprofen granules and tablets in healthy volunteers.

The bioavailability of granules and tablet flurbiprofen in 100 mg single dose was crossover compared in 6 healthy volunteers (mean aged 26.8 years). The granules showed an earlier peaktime and a lower maximum concentration than the tablet. Area under the curve and half-time in terminal phase were similar, with the granule relative bioavailability of 0.98.

Adult↗

HLA and hormonal studies in 5 patients with late-onset 21-hydroxylase deficiency syndrome (21OHDS).

Late-onset 21-hydroxylase deficiency (21OHD) presents biochemical evidence of 21OHD and virilization in peri-or postpubertal age; it has been demonstrated that late-onset 21OHD is linked to HLA system. We present the HLA typing, the baseline and the ACTH-stimulated hormonal levels in 5 patients with late-onset 21OHD and in their family members. We identified 3 HLA identical male sibs within their respective families, 2 sibs sharing one haplotype with the affected member and 2 homozygous normal sibs. We observed elevated baseline (greater than 4 ng/ml) and ACTH-stimulated 17-hydroxyprogesterone levels, increased baseline Androstenedione levels, slightly elevated or normal DHEA-S and Testosterone values and subnormal response of Cortisol levels to ACTH in patients and in the HLA-identical sibs, reduced SHBG levels in patients but not in their identical sibs. The heterozygous family members presented hyperresponsiveness of 17-hydroxyprogesterone but not of androgens after ACTH. We confirm that late-onset of 21OHD is an autosomal recessive disease linked to HLA-B; there is in fact biochemical evidence of mild 21OHD in patients and in their HLA identical sibs and 17-hydroxyprogesterone levels in the range of heterozygotes for classical 21OHD in parents and sibs predicted by HLA to be carriers. Thus HLA typing and hormonal data, particularly 17-hydroxyprogesterone, are useful, also in this form of congenital hyperplasia, in detecting heterozygotes.

17-alpha-Hydroxyprogesterone↗

Renin-angiotensin-aldosterone system: a long-term follow-up study in 17 alpha-hydroxylase deficiency syndrome (17OHDS).

We studied the mineralocorticoid pattern in 4 patients with 17OHD during long-term glucocorticoid treatment. We observed reduction of BP, normalization of K levels, a gradual increase in PRA and in urinary Aldosterone (ALDO); a normal response of plasma ALDO to ACTH and to angiotensin II was present only in one case. We observed a prompt decrease of mineralocorticoid hormones, normalized by long-term therapy only in one case. Discontinuation of treatment induced an increase of ALDO that became suppressed in late off-treatment. Thus, glucocorticoid treatment decreases abnormal steroid levels and activates zona glomerulosa (ZG) function, even if it may take years for ALDO to normalize. Brief discontinuation of therapy induces a surge in ALDO levels, revealing no biosynthetic defect in ZG, while in late off-treatment mineralocorticoids seem to come exclusively from zona fasciculata.

Adolescent↗

Pharmacokinetics of two new oral formulations of ibuprofen.

Two new formulations of ibuprofen were studied in 600 mg coated tablets and granules, to allow an easier adjustment of its daily dosage now higher than in the past. Six healthy volunteers (3M and 3F, mean age 32.6 years took part in a 6 X 6 Latin Square single dose pharmacokinetic study comparing six oral formulations of ibuprofen: 600 mg coated tablets, 300, 400 and 600 mg resinated granules, 300 and 400 mg sugar-coated tablets available on the market as Brufen. The results show that there is a correlation between dose and the area under the blood concentration-time curve. The availability of ibuprofen was similar irrespective of whether it is given in the form of granules or in tablets. The short half-life and the widespread use of ibuprofen give an acceptable range of safety to these new formulations.

Administration, Oral↗

Usefulness of dynamic reno-scintigraphy in the follow-up of patients treated by surgery or percutaneous transluminal angioplasty for renovascular hypertension.

The aim of this study was to assess the role of dynamic reno-scintigraphy (DRS) in follow-up of 21 hypertensive patients who underwent surgery or percutaneous transluminal angioplasty (PTA) for renal artery stenosis. Dynamic reno-scintigraphy was recorded following injection of 0.12 mCi/kg 99Tcm-glucoheptonate i.v. before and after reconstructive vascular surgery or PTA. Serial images and renal time activity were analysed according to established criteria of interpretation. In terms of blood pressure response, 14 patients were cured or improved after surgery or PTA; DRS normalized or markedly improved in all these cases. Dynamic reno-scintigraphy did not change in seven patients who did not benefit from surgery or PTA. In three of them, repeated angiography showed, respectively, a by-pass occlusion, a renal artery re-occlusion after PTA, and a renoparenchymal disease. Dynamic reno-scintigraphy appears to reflect well the recovery of renal perfusion in patients treated by surgery or PTA for suspected renovascular hypertension.

Adult↗

Pharmacokinetics of oral and rectal flurbiprofen in children.

Eight subjects, aged 6-12 years and weighing 18.8-36.7 kg, received single doses of flurbiprofen 50 or 75 mg (corresponding to 1.4-2.7 mg/kg) as syrup and suppository in a Latin square design. Half-life (2.7-3.2 h), elimination constant (0.22-0.26 h-1), area under the plasma level curve (72.4-77.3 micrograms X h X ml-1) and time to reach the concentration peak (1-0.75 h) were similar after the syrup and suppository. Flurbiprofen showed equivalent bioavailability after oral and rectal administration and the same pharmacokinetic profile was confirmed in children as observed in adults.

Administration, Oral↗

Delta infection and liver disease in hemophilic carriers of hepatitis B surface antigen.

The prevalence of infection with hepatitis B virus (HBV)-associated delta (delta) agent was assessed in 277 treated hemophiliacs (primarily adolescents and adults) and 24 treated hemophilic children. Hemophiliacs who carry hepatitis B surface antigen (HBsAg) are at high risk of delta infection. Antibody to delta (anti-delta) was found in 14 (49%) of 29 HBsAg-positive adult or adolescent hemophiliacs and four (25%) of 16 HBsAg-positive hemophilic children; it was identified in none of the patients without serologic evidence of exposure to HBV and only occasionally and in low titers in hemophiliacs convalescent from HBV infection. Either histologic or biochemical evidence of chronic hepatitis was found in 10 (56%) of 18 HBsAg-positive hemophiliacs with anti-delta. In two patients with anti-delta a potentially pathogenic role for delta was suggested by the intrahepatic expression of delta antigen, detected by immunofluorescence. It appears that delta infection is a major cause of chronic liver disease in hemophiliacs.

Adolescent↗

Peripheral and renal vein plasma renin activity in hypertensive urological patients.

Upright plasma renin activity (PRA) was measured in 112 patients suffering from urological diseases associated with hypertension, and was found to be predominantly low. In 40 cases with normal or elevated peripheral PRA, renal venous PRA was measured and their ratios calculated. There was a significant decrease of blood pressure in 14 patients who had undergone surgery and both ratios were significant. The patients whose blood pressure remained unchanged had no significant renal vein PRA ratios. However, one case with nonlateralising renal venous PRA ratios responded well to surgery. It is concluded that although peripheral vein PRA is of limited value in hypertension associated with urological diseases, the measurement of PRA in renal vein plasma offers, in a number of cases, useful prognostic information.

Adult↗

Circadian secretion of ACTH, cortisol, and mineralocorticoids in Cushing's syndrome.

The behaviour of plasma levels of ACTH was studied in five untreated patients with pituitary-dependent Cushing's syndrome, with blood samples taken every half an hour for a total period of 24 hours; plasma cortisol, corticosterone, deoxycorticosterone (DOC) and aldosterone were also measured simultaneously. In all cases, above normal secretory impulses of ACTH and cortisol, at approximately the same height, were present throughout the day, while between these peaks the levels were in the normal range. Few peaks of ACTH and cortisol were simultaneous and rare secretory impulses of corticosterone, and deoxycorticosterone were in synchrony with those of ACTH or cortisol. DOC levels were found to have some peaks above normal levels while corticosterone levels presented rare elevated peaks during the day. Plasma aldosterone values on the other hand, were extremely low in all except in one case, where the variations may be interpreted as pure fluctuations. These findings confirm that: 1) In a number of cases, multiple samples of ACTH and cortisol (during the 24 hrs.) appear to be essential in order to distinguish pituitary-dependent Cushing's syndrome from normal; 2) In conditions of ACTH excess, DOC and corticosterone secretion seems to become progressively less ACTH-dependent as we proceed down the biosynthetic chain towards aldosterone, which is suppressed in most cases.

Adolescent↗

HLA genotypes and HLA-linked genetic markers in Italian patients with classical 21-hydroxylase deficiency.

HLA genotype and HLA-linked marker data for 40 unrelated patients from central Italy and 2 unrelated patients from Sardinia with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH-def) were analyzed. The results confirm that the HLA-linked 21-OH-def gene is associated with several different HLA determinants and complete HLA haplotypes, although the only determinant with significantly increased frequency was the complement C2 allele C2B. The HLA antigens B8 and DR3 were found in significantly decreased frequencies. The haplotype A3, Cw6, Bw47, BfF, DR7, which is exceptionally rare in the general population but which has been found in many other 21-OH-def patients from diverse geographical origins, was also found in one of the Italian patients. This and other HLA haplotype associations found among the Italian patients may represent mutations that have occurred on HLA haplotypes with genetic linkage disequilibrium or, alternatively, may represent mutations that have not yet had time to become randomly associated with different HLA complex determinants. The marked negative associations with B8 and DR3 could, however, result from an interaction between the gene products of the HLA complex and the 21-OH-def phenotype.

Adrenal Hyperplasia, Congenital↗

Effect of angiotensin II and converting enzyme inhibitor (captopril) on blood pressure, plasma renin activity and aldosterone in primary aldosteronism.

1. Patients with idiopathic hyperaldosteronism (IHA) show a response of aldosterone to posture which is not present in patients with aldosterone-producing adenoma (APA). We have determined whether this could be explained by a different sensitivity to angiotensin II. 2. Angiotensin II was infused in gradually increasing doses in six patients with APA and in seven patients with IHA. No changes in aldosterone concentration were found at the end of each period in APA, whereas there was a significant increase in IHA; blood pressure rose by a similar extent in both groups. 3. In order to evaluate the role of endogenous angiotensin II, captopril, a converting enzyme inhibitor, was administered to six patients with APA and five patients with IHA at a dose of 75 mg/day for 1 week. There was a significant fall of mean blood pressure in IHA and only minimal changes in APA. Plasma renin activity and plasma in urinary aldosterone were unchanged in APA. In IHA there was a small increase in upright plasma renin activity and a slight decrease in both plasma and urinary aldosterone, but these changes were not significant. 4. These findings further support the idea that idiopathic hyperaldosteronism is a clinical state different from that occurring in primary aldosteronism due to adenoma, and may be more closely related to essential hypertension.

Aldosterone↗

Genetic and hormonal characterization of cryptic 21-hydroxylase deficiency.

Cryptic 21-hydroxylase deficiency has been previously described in asymptomatic family members of patients with classical congenital adrenal hyperplasia (CAH). These family members were detected by high baseline 17-hydroxyprogesterone levels found in the course of family studies. The hormonal responses to ACTH of the family members with cryptic 21-hydroxylase deficiency were determined and compared to the responses of patients with CAH, patients with acquired adrenal hyperplasia, family members predicted to be heterozygous for CAH, family members predicted to be unaffected, and the general population. The ACTH-stimulated levels of 17-hydroxyprogesterone and delta 4-androstenedione in the cryptic family members were elevated above the level of the general population or family members heterozygous for classical CAH, but below that of patients with CAH. The hormonal profile of patients with cryptic 21-hydroxylase deficiency is similar to that of patients with acquired adrenal hyperplasia. The response of family members heterozygous for the cryptic gene (21-OH CRYPTIC/21-OH NORMAL) was indistinguishable from that of family members heterozygous for the classical CAH gene (21-OH CAH/21-OH NORMAL). These studies support our previous proposal that patients with cryptic 21-hydroxylase deficiency are genetic compounds, having one gene for a severe enzyme deficiency and one gene for a mild 21-hydroxylase deficiency. Thus, the 21-hydroxylase genotype in cryptic 21-hydroxylase deficiency is 21-OH CAH/21-OH CRYPTIC.

Adolescent↗

[Surgical and medical treatment of renovascular hypertension (author's transl)].

We have studied a group of 47 patients with unilateral or bilateral renal artery stenosis; 27 of them have been operated, while 20 have been subjected to medical treatment. Among the surgically treated patients, 18 out of the 22 cases with an unilateral stenosis had satisfactory results and didn't assume any treatment after surgical cure. All the 5 cases of bilateral stenosis presented a regular blood pressure after surgery. Nine among the 12 patients affected by unilateral stenosis and 3 among the 8 patients presenting bilateral forms who received medical treatment had successful results with the conventional therapy. The parameters that seems give a better prognostic indication for the surgical cure are either significant renal veins renin ratios (Ra/Rc and Rc/P), either high peripheral PRA values combined with a renal artery stenosis greater than or equal to 70%, in all the cases without evident damages in the opposite kidney, even if the renin ratios are not significant. The results of the medical treatment may be predicted from the entity of the renal stenosis. Failures are more likely to occur in the bilateral forms. In these cases the most satisfactory results can be obtained using minoxidil or the inhibitor of the converting enzyme of angiotensin I.

Adolescent↗