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Biomedical subjects

F Sciarra

Publications and source records attributed to F Sciarra.

At least 37 records · Page 2Linked to original sources
PubMed1992

Plasma 19-hydroxy-androstenedione (19-OH-A) in essential hypertension.

19-hydroxy-androstenedione (19-OH-A), a C19 steroid, is an amplifier of the sodium retaining action of aldosterone under the control of ACTH and renin-angiotensin system. These findings suggest that 19-OH-A may be involved in the regulation of hydroelectrolyte balance and blood pressure. Aim of the present study was to examine the behaviour of 19-OH-A in normal volunteers (N) and in patients with Essential Hypertension (EH) in basal conditions and after dynamic tests such as postural changes, physical exercise and ACTH administration. The significant increase in 19-OH-A after ACTH confirms its adrenal origin. During bicycle exercise the significant increase in plasma catecholamines, renin-activity, aldosterone, blood pressure and heart rate at maximum effort was not associated with a parallel increase in 19-OH-A. No significant differences were found in plasma 19-OH-A levels between N and EH patients both in basal conditions and after dynamic tests. Therefore, our findings seem to exclude an important role of 19-OH-A in the pathogenesis of EH.

Adrenocorticotropic Hormone↗
PubMed1991

Plasma catecholamine responses during a personalized physical stress as a dynamic characterization of essential hypertension.

High performance liquid chromatography (HPLC) with electrochemical detection proves to be a reliable method for determination of plasma catecholamines (CA) to assess the possible role of the sympathetic nervous system (SNS) in essential hypertension (EH). The present investigation in a group of 15 normotensive (N) and 13 stable EH patients, homogeneous for age and duration of hypertension, was carried out without treatment in the supine position, up-right position and during a personalized bicycle exercise. Mean blood pressure, mean heart rate, plasma renin activity and plasma aldosterone were also evaluated at the various exertion phases. Norepinephrine (NE) and epinephrine (E) showed a progressive increase in N and in EH patients, reaching the highest values at maximum effort. However, EH patients showed higher E plasma levels than N before maximum effort. Dopamine (DA) reached the highest values in N at maximum effort and in EH patients at recovery time. These findings allow us to foresee the possibility of a better characterization of the SNS role in EH.

Adult↗
PubMed1990

Antiandrogens: clinical applications.

Antiandrogens, preventing androgen action at target tissue level, are used in the treatment of various androgen-dependent diseases. Pharmacologically these substances have either a steroidal structure, like cyproterone acetate (CPA) and spironolactone (SPL), or a non-steroidal structure, like flutamide (FLU). In women with hyperandrogenism (PCO syndrome, idiopathic hirsutism, acne), clinical benefit may be obtained with CPA, which also displays a progestational activity and an antigonadotropic effect. CPA (25-50 mg/day) is used in combination with ethinyl-estradiol (EE) (20-30 micrograms/day) in reversed sequential regimen. SPL, less effective than CPA may be employed in moderate hirsutism and acne at dosages of 100-200 mg/day. During SPL treatment menstrual irregularities are frequent: in this case an association with oral contraceptives is indicated. SPL + bromocriptine (2.5-5 mg/day) has been experienced with success in PCO syndrome. The pure antiandrogen FLU, inducing progressive increase in LH and testosterone secretion, may be used only in combination with oral contraceptives. In men antiandrogens have been tested in BPH and prostatic carcinoma. In BPH the decrease in nuclear receptors and DHT nuclear content during CPA or FLU may represent the rational base of the medical treatment. An improvement in urinary obstructive manifestation has been observed with CPA alone or associated with tamoxifen (100 mg + 100 mg day). In advanced prostatic carcinoma antiandrogens represent a good alternative to estrogen therapy with less side effects and in combination with surgical or medical castration (LH-RH analogues) achieve a complete androgen blockade. An increase in the percentage of remissions and survival has been reported.

Acne Vulgaris↗
PubMed1990

Advanced prostatic cancer: clinical and hormonal response to flutamide in patients pretreated with LHRH analogue and cyproterone acetate.

The aim of the present investigation was to establish whether in advanced prostatic carcinoma in relapse treated with LHRH analogues combined with cyproterone acetate (CPA), substitution of this antiandrogen with another compound such as flutamide (FLU) might lead to further subjective and objective improvement. The present randomized study was carried out on 100 patients in relapse treated with long acting LHRH analogue + CPA: 52 patients were submitted to combination therapy with FLU, whilst the remaining 48 cases continued with CPA treatment. Plasma levels of gonadotropin FSH-LH, androstenedione and dehydroepiandrosterone sulphate were significantly reduced by both treatments, testosterone fell to castration values, but prolactin showed no change. Progress of the disease was confirmed in all the patients who continued with CPA treatment with a median survival rate of 9.3 +/- 2 months from the start of the second cycle of CPA. In the FLU-treated group, the overall objective response differed significantly in relation to the stage of the disease. In fact, in stage D2, the response was poor with a median survival of 12 +/- 2 months, which is almost comparable to that in the CPA group. In stage D1, a clinical improvement, even if of short duration, was observed in almost 50% of the cases with a median survival of 18 +/- 3 months. Good results were also obtained in undifferentiated tumours, FLU probably acting as an antimitotic agent. Moreover, FLU also exerted an analgesic effect, with relief of bone pain in 65% of the cases in stage D2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Incidental prostatic carcinoma: four-year follow-up after treatment with cyproterone acetate.

This report is a retrospective clinical randomized study carried out on 114 cases of incidental prostatic carcinoma aged 55-87 years, 58 untreated and 56 treated with cyproterone acetate (CPA 200 mg/day) for 6 months, immediately after surgery. 78 cases were staged A1 and the remaining 36 A2. In stage A1, 75 cases were histologically graded G1, and 3 G2, whereas in stage A2, 7 cases were G1, 19 G2 and 10 G3. Moreover, flow cytometric DNA analysis showed in A1 20 G1 carcinomas with nuclear diploidy and 3 G2 with nuclear aneuploidy, in stage A2, 4 G3 tumors with nuclear aneuploidy. During the 4-year follow-up, 25/28 patients of the untreated group and 15/56 of the CPA-treated group were found in progression. In A1, progression was found in 6/37 untreated patients and 5/41 CPA-treated, whilst in A2 progression was observed in 19/21 untreated patients and in 10/15 treated with CPA. The critical period for progression was between the 2nd and 3rd year of follow-up. In A1, therefore, 6 months of therapy with CPA does not modify the progression rate, which is significantly improved in A2 (66% in the treated and 90% in the untreated group) during the first 30 months of follow-up. The prognosis may probably be further improved by continuing endocrine therapy.

Aged↗
PubMed1990

Zoladex vs. Zoladex plus cyproterone acetate in the treatment of advanced prostatic cancer: a multicenter Italian study.

A collaborative multicenter trial was conducted by 17 Italian groups to verify whether the so-called total androgen blockade obtained with luteinizing hormone releasing hormone (LHRH) analogs combined with antiandrogens is more effective than conventional monotherapy in the treatment of advanced prostatic cancer. A total of 328 previously untreated patients were evaluated: 163 patients received Zoladex depot alone, 3.6 mg subcutaneously every 28 days, and 165 patients received Zoladex depot plus cyproterone acetate (CPA), 200 mg/day orally. The follow-up period ranged from 41-251 weeks. Treatment was well tolerated, and side-effects in both groups mainly comprised loss of libido and erections, hot flashes and breast swelling and tenderness. There was no significant difference in objective response after 6, 12 and 24 months of treatment between the 2 groups. Median time to disease progression was comparable in both groups: 55 weeks in the Zoladex group and 54 weeks in the Zoladex plus CPA group. The time to disease progression and the survival distribution was comparable in both groups. Although there were no significant differences in the overall subjective response to both treatments, a faster improvement, with respect to pain and performance status was noted in the Zoladex plus CPA group (8 weeks) compared to Zoladex alone (12 weeks). The addition of antiandrogen, by inhibiting the initial elevation of plasma testosterone, may prevent the disease flare-up which occurs in a small number of patients during the first few days of treatment with LHRH analogs alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1990

Ovarian 17-ketosteroid reductase deficiency as a possible cause of polycystic ovarian disease.

The deficiency of ovarian 17-ketosteroid reductase (17-KSR) was recently discovered to be a possible cause of polycystic ovarian disease (PCOD) in hirsute women. Forty three patients with PCOD (age range, 18-38 yr) were reevaluated to search for a hormonal pattern that might suggest an ovarian 17-KSR deficiency. Androstenedione, testosterone, FSH, LH, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate were evaluated basally on the day 17 of the menstrual cycle, when present, and after dynamic tests (ACTH stimulation, 1 mg im for 2 consecutive days; dexamethasone inhibition, 0.5 mg four times a day for 14 days; and cyproterone acetate treatment, 50 mg each day for 14 days) in three successive menstrual cycles or at 30-day intervals. All patients studied presented with hyperestronemia, abnormal gonadotropin pattern, and hyperandrogenism, but showed different responses of androstenedione and testosterone to dynamic tests. In two patients the hormonal pattern suggested an ovarian 17-KSR deficiency: in fact they showed plasma values of androstenedione (22 and 31.3 nmol/L, respectively) and estrone (628 and 849 pmol/L, respectively) that were greatly increased compared with other patients and with controls. Androstenedione did not increase after ACTH stimulation (21.5 and 32.1 nmol/L, respectively) and did not decrease after dexamethasone inhibition (21 and 29 nmol/L, respectively), but only decreased after cyproterone acetate treatment (8 and 10.8 nmol/L, respectively). An hCG test, performed during dexamethasone suppression, confirmed the diagnosis of ovarian 17-KSR defect in one of these two patients (patient 1). Two of three brothers of patient 1 (aged 25 and 34 yr) presented with persistent important pubertal gynecomastia; one brother also had severe oligospermia. These clinical findings and the high values of androstenedione/testosterone (0.85) and estrone/estradiol (4.1) ratios of baseline plasma levels compared with controls (0.18 and 2.1, respectively) suggested a partial testicular 17-KSR deficiency. Five other patients showed PCOD secondary to nonclassic 21-hydroxylase defect diagnosed on the basis of high 17-hydroxyprogesterone plasma values and highly responsive to ACTH. The remaining 36 patients showed increased values of androstenedione and testosterone after ACTH stimulation and a decrease of these two parameters after both dexamethasone inhibition and cyproterone acetate treatment. The discovery of the 17-KSR deficiency in men and women in the same family demonstrates genetic control of this enzyme similar in both sexes, confirming the hypothesis that this disorder is inherited as an autosomal recessive character. Finally, it is strongly supported that ovarian 17-KSR defect may cause a syndrome closely resembling PCOD.

17-Hydroxysteroid Dehydrogenases↗
PubMed1990

[Improvement in the accuracy of diagnosis of ischemic heart disease with simultaneous radioisotope evaluation of regional myocardial function perfusion and an exercise test].

The recently developed myocardial agent methoxy-isobutyl-isonitrile (MIBI), labelled to 99mTc, allows one to evaluate global and regional ventricular function as well as myocardial perfusion by means of a single exercise stress test, significantly increasing diagnostic accuracy for coronary artery disease. Between September 1988 and March 1989, 407 patients with either suspected or already ascertained coronary artery disease underwent simultaneous assessment of regional ventricular function with first pass radionuclide angiography, and of myocardial perfusion with single photon emission computerized tomography, by means of 2 injections of 99mTc-MIBI at rest and at peak of the same exercise test. Out of these patients, 56 (52 men and 4 women, whose mean age was 57 +/- 7 years) underwent coronary angiography within 6 months of radionuclide examination and were included in the study. There were 13 1-vessel, 26 2-vessel and 17 3-vessel disease patients. Thirty-six of them had had a previous (greater than 6 months old) myocardial infarction, on the anterior wall in 16 patients, on the inferior wall in 20. In all patients a computerized bicycle stress test was performed; interruption criteria were ST segment depression greater than or equal to 1 mm in 27 patients (48%), the achievement of a heart rate greater than 85% of maximal age-predicted heart rate in 12 patients (22%) and fatigue in 17 patients (30%). Scintigraphic results were compared to angiographic findings: global sensitivity and specificity of the simultaneous evaluation were 82% and 81%, respectively, vs 95% and 56% of functional results and 85% and 71% of perfusion results, respectively. Regional analysis was also performed, by dividing scintigraphic images into the territories supplied by the 3 main coronary vessels, i.e., left anterior descending artery (LAD), left circumflex artery (LCx) and posterior descending artery (PD). On LAD territory the simultaneous evaluation achieved a sensitivity of 88% and a specificity of 63%, vs 98% and 38% of functional analysis and 88% and 50% of perfusional analysis, respectively. On LCx territory sensitivity and specificity were respectively 71% and 96%, vs 91% and 64% of function, and 77% and 96% of perfusion alone. On PD territory sensitivity was 85%, vs 94% and 91%, respectively; specificity was 73%, vs 55% and 55%, respectively. Combined functional and perfusional analysis achieved a 68% sensitivity in identifying less than or equal to 75% coronary narrowings, and a 90% sensitivity for greater than 90% narrowings.(ABSTRACT TRUNCATED AT 400 WORDS)

Coronary Disease↗
PubMed1990

[Changes in R wave voltage during exercise: are they a sign of changes in ventricular volume or of myocardial ischemia?].

In an attempt to assess the significance of R wave amplitude changes during exercise in patients with coronary artery disease, we retrospectively analysed radionuclide as well as exercise test results of 147 patients with either suspected or already ascertained coronary artery disease, 126 men and 21 women, whose mean age was 56.0 +/- 9.3 years, 56 of which with previous myocardial infarction (16 on the anterior, 33 on the inferior and 7 on the lateral wall), who underwent a simultaneous evaluation of regional ventricular function by means of first pass angiography with multielement gamma-camera and of myocardial perfusion by means of single photon emission computerized tomography. All patients received 2 iv injections of 99mTc-methoxy-isobutyl-isonitrile at rest and at peak of a computerized bicycle stress test, whose end-points were ST segment depression greater than or equal to 1 mm or the attainment of a heart rate greater than 85% of maximal age-predicted one. R wave amplitude was measured by means of a magnifying lens on an averaged ECG complex, selecting for each patient the precordial lead showing the largest R wave amplitude. Absolute values of left ventricular volumes were computed by means of a standardized method from first pass angiography data. Patients were divided in subgroups according to the presence and to the number of coronary territories with evidence of stress-induced myocardial ischemia at radionuclide study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Epidermal growth factor binding and steroid receptor content in human benign prostatic hyperplasia.

The receptor for epidermal growth factor (EGF-R) was characterized on membrane fractions from human benign prostatic hyperplasia (BPH). Specific binding of [125I]EGF reached equilibrium after 40 min at 25 degrees C and was stable for up to 120 min. Saturation analysis of EGF-R, performed by incubating the membranes with 0.0156-15 nM [125I]EGF in the presence and in the absence of 100-fold excess of cold EGF for 60 min, revealed the presence of two classes of binding sites with high and low affinities (Kd = 0.35 +/- 0.23 and 9.60 +/- 2.87 nM respectively). Competition experiments revealed that FSH, insulin and calcitonin did not compete with [125I]EGF. The simultaneous determination of EGF-R and that of estradiol (ER), progesterone (PR) and androgen receptors (AR) was performed using the same buffer to homogenate the tissues and to obtain cellular membranes. The steroid receptors (SR) were determined by means of the dextran-coated charcoal method. There was a significant negative correlation between nuclear SR and binding capacity of EGF-R. The presence of specific and high affinity binding sites for EGF and the modulation of the level of these sites by steroid receptors suggest a possible role of EGF in prostatic hyperplasia.

Biomarkers↗
PubMed1988

Effects of two different medical treatments on dihydrotestosterone content and androgen receptors in human benign prostatic hyperplasia.

In order to evaluate the biochemical modifications induced by hormonal treatments on human prostatic tissue, the intracellular distribution of tissue DHT and AR were investigated in BPH patients untreated and treated (25-30 days before surgery) with the association of cyproterone acetate (CPA), 100 mg p.o./day plus tamoxifen (TAM), 100 mg p.o./day, or with flutamide (FLU) alone, 750 mg p.o./day. Dextran-coated charcoal and exchange assay in the presence of sodium molybdates (0.2 M) were used for AR determination, employing methyltrienolone as radioligand in the presence of triamcinolone acetonide. Endogenous DHT was measured by RIA, after ether extraction and purification on celite microcolumns. The treatment with CPA plus TAM led to a detection of cytosol AR (ARc) in 50% of the specimens, while nuclear AR (ARn) were never measurable. The FLU treatment did not modify the incidence of ARc, while ARn was not detectable. The cytosolic and nuclear compartmentalization of DHT was scarcely affected by the combined CPA plus TAM treatment, while FLU treatment induced a prevalent cytosolic localization of DHT (DHTc = 283.2 +/- 24.6 S.E. and DHTn = 1138.4 +/- 98.7 S.E. pg/mg DNA in untreated patients; DHTc = 350.4 +/- 97.7 S.E. and DHTn = 589.7 +/- 154.4 S.E. pg/mg DNA in CPA plus TAM treated patients; DHTc = 1101.7 +/- 165.7 S.E. and DHTn = 733.0 +/- 93.9 S.E. pg/mg DNA in FLU treated patients). Both medical treatments, therefore, were able to reduce prostatic growth on account of the reduced value of nuclear DHT content.

Androgen Antagonists↗
PubMed1987

[Hormonal and psychophysiologic responses under conditions of experimental stress in subjects with essential arterial hypertension].

Two sex balanced groups of 6 subjects each (hypertensive patients vs normotensive subjects) were monitored for both biochemical and psychophysiological variables under stress (PRA, Adrenal Corticosteroid, Aldosterone, HR and Blood Pressure). A computed controlled RT procedure was employed as stress stimulation. The results suggest that different coping mechanisms are present in hypertensives and normotensives. Hypertensives were more emotionally involved and less efficient in stimulus habituation. Biochemical mechanisms have been hypothesized to explain these differences.

Anxiety↗
PubMed1987

Lack of correlation between sex hormone binding globulin and free testosterone in some cases of "idiopathic" hirsutism.

Plasma 3 alpha-androstanediol levels are increased in a high percentage of hirsute women, including those with normal plasma levels of its precursors, repeatedly evaluated during the menstrual cycle. To better ascertain the origin of this form of hirsutism, so called "idiopathic", 17 hirsute women (aged 19.5 +/- 4.8 SD yr), with normal bw, showing an isolated increase in plasma 3 alpha-androstanediol (0.65 +/- 0.18 SD nmol/l) were studied in basal conditions (on day 6, 7, 17, 18 of the menstrual cycle). A hirsute female (aged 14 yr) with congenital adrenal hyperplasia due to 21-hydroxylase deficiency was also included in the protocol. Sex hormone binding globulin was evaluated using a saturation method (dihydrotestosterone- 3H 0.5-25 nM) with and without 200x cold dihydrotestosterone. Maximum number of binding sites and Ka were calculated in all cases with Scatchard analysis. Free testosterone was evaluated by the equilibrium dialysis technique. The results obtained showed a significant increase in Ka values in 10 out of the 17 cases; low plasma levels of sex hormone binding globulin in 13 cases and normal levels in 4 cases; high levels of free testosterone fraction in 5 cases and in the upper limits of the normal range or normal in the remaining 12. These findings demonstrate that some cases of "idiopathic" hirsutism may present an alteration in the binding affinity of the sex hormone binding globulin which may be genetically transmitted, being found to be increased in two sisters and in their brother.

Adolescent↗
PubMed1987

Testicular responsiveness following chronic administration of hCG (1500 IU every six days) in untreated hypogonadotropic hypogonadism.

The observation that the testosterone (T) response to a single intramuscular injection of hCG is prolonged suggests that currently used regimens (2-3 injections per week) to stimulate endogenous androgen secretion in hypogonadotropic hypogonadism (HH) patients have to be reassessed. Moreover, during the last few years, Leydig cell steroidogenic desensitization has been found after massive doses of hCG. The aim of the present investigation, carried out in 6 HH patients who showed no signs of puberty, was to study the effect of 1500 IU hCG administered every six days over a period of one year to induce the onset of pubertal development. To evaluate the kinetics of the response of T, 17 alpha-hydroxyprogesterone (17 alpha-OHP) and 17 beta-oestradiol (E2), blood samples were taken basally and 1, 2, 4 and 6 days after drug injection. This dynamic study was performed after the first injection and after the 4th and 12th month of treatment. During this one year time period, a progressive increase in testicular size was observed. Comparing plasma T levels (mean +/- SE) before the first injection (11.2 +/- 4.7 ng/dl) with the corresponding values at the 4th (38.7 +/- 10.5 ng/dl) and 12th months (99.5 +/- 19.9 ng/dl) of therapy, a progressive and significant increase was observed. T reached a maximum elevation 58 hours after hCG injection at the 4th month (198.3 +/- 42 ng/dl; P less than 0.01) and at the 12th month (415.6 +/- 62.6 ng/dl; P less than 0.05), whereas it remained unchanged following the first hCG injection.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1986

Therapeutic approaches in prostatic cancer.

Surgical castration combined to cyproterone acetate treatment in patients with advanced prostatic carcinoma, gives satisfactory clinical results in 75% of the cases, with a follow-up period of 12-59 months. Histological tumour grading, tissue dihydrotestosterone (DHT) concentrations and DNA distribution by flow-cytometry in the tumoral cells are significantly correlated with the clinical response to hormonal therapy, whilst cytosol androgen receptors are not. 17 cases with DHT levels greater than 1.8 ng/g tissue are in remission (COR, POR or OS), whereas 5 cases with DHT levels less than 1.8 ng/g are in progression. In the responder group diploid DNA pattern is found in 20 cases and aneuploidy in 7, whilst in the not responder group aneuploidy was found in 5 cases and diploidy in 2. In conclusion histological grading and measurement of DNA and DHT in tumour tissue may be complementary in the prospective identification of the hormonally dependent tumours, which may benefit of the combined endocrine therapy suppressing androgens of testicular and adrenal origin.

Aged↗
PubMed1985

Familial male pseudohermaphroditism with gynaecomastia due to 17 beta-hydroxysteroid dehydrogenase deficiency. A report of 3 cases.

Three sisters with male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency are described. On the basis of a 46 XY karyotype and female phenotype all subjects were thought to have the testicular feminization syndrome. At puberty the two older patients developed signs of virilization and gynaecomastia. In these patients the plasma androstenedione level was 4-5 times higher than normal, whilst the plasma testosterone level was low compared to the normal range and, under basal conditions, their plasma androstenedione to testosterone ratio was 20-25 times higher than normal. Interestingly, in the third, prepubertal case, the basal androstenedione to testosterone ratio was normal but became six times higher than normal after hCG stimulation. These data support the diagnosis of male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency and underline the diagnostic value of the hCG stimulation test prepubertally.

17-Hydroxysteroid Dehydrogenases↗