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Biomedical subjects

A Angeli

Publications and source records attributed to A Angeli.

At least 19 recordsLinked to original sources
PubMed1992

Favorable response of metastatic adrenocortical carcinoma to etoposide, adriamycin and cisplatin (EAP) chemotherapy. Report of two cases.

The usefulness of non-specific chemotherapy for advanced adrenocortical carcinoma (ACC) is controversial. We report on 2 young female patients (25 and 19 yr) who presented with a clinical picture of Cushing's syndrome due to histologically confirmed ACC. The first patient underwent radical surgery, but after a disease-free interval of 6 months a local recurrence was apparent. She was reoperated and treated with 6 courses of cisplatin and etoposide chemotherapy. Mitotane (8 g daily) was begun, but 2 months later debulking surgery was again performed. A second-line chemotherapy with the etoposide, adriamycin, cisplatin (EAP) scheme attained a partial remission lasting 7 months, then metastatic spread to the brain led to death of the patient. The survival time was 30 months. The second patient underwent radical surgery and adjuvant mitotane (4 g daily), but multiple lung and mediastinal metastases were diagnosed after an interval of 29 months. Chemotherapy with the EAP regimen (6 courses) without interrupting mitotane attained a partial remission lasting 21+ months. We suggest that the EAP scheme is active in advanced ACC and that its association with mitotane is feasible.

Adrenal Cortex Neoplasms↗
PubMed1992

Association of cyst type with risk factors for breast cancer and relapse rate in women with gross cystic disease of the breast.

The concentration of potassium (K+) and sodium (Na+) was measured in breast cyst fluid (BCF) from 611 cysts greater than 3 ml aspirated in 520 women with gross cystic disease of the breast. These women were enrolled, from 1983 on, in a cohort study aimed at assessing the relationship between cyst type, as defined by the K+/Na+ ratio in BCF, and the risk of breast cancer. The inverse relationship between K+ and Na+ and the bimodal distribution of the K+/Na+ ratio in BCF were confirmed. Type I cysts were defined as cysts with a K+/Na+ greater than 1.5 in BCF. Among women with type I cysts, a higher proportion of women with one or no births, of women with a history of apocrine cysts, of current smokers, and of women who do not drink coffee was found, as compared to women with other types of cysts. The risk of cyst relapse was significantly higher among women with type I cysts than among women with other types of cysts and among women with multiple cysts at presentation. These findings indicate that type I BCF is a marker of "active" gross cystic disease of the breast and suggest that it may be associated with increased breast cancer risk.

Abortion, Spontaneous↗
PubMed1992

Categorization of cysts and steroid levels in breast cyst fluid.

Several reports indicate that patients with macrocysts have a two- to fourfold higher risk of developing cancer. The fluid filling the cysts (breast cyst fluid, BCF) contains unusual amounts of biologically active substances, including hormones and metabolites. The accumulation of steroid conjugates, such as androgen and estrogen sulfates, deserves interest. Measuring BCF cations (K+, Na+) permits classification of cysts into two major subsets (type I and type II), conceivably associated with a different degree and with a turnover of apocrine cells in the lining epithelium. Type I (high K+/Na+ ratio) and type II (low K+/Na+ ratio) cysts display different patterns of steroid analytes and steroid-binding proteins. There are many gaps in our understanding of the relationship between local steroids and hypersecretion of fluid in the terminal duct lobular units with eventual appearance of cysts. Accumulating biochemical and epidemiological data, however, point to recurrent, multiple type I cysts as a marker of endocrine risk, i.e., of a whole-organ promoting status toward proliferative premalignant lesions.

Breast Neoplasms↗
PubMed1991

Hyperthyroidism due to a pituitary adenoma composed of two different cell types, one secreting alpha-subunit alone and another cosecreting alpha-subunit and thyrotropin.

A 37-yr-old female presented with clinical signs and symptoms of mild hyperthyroidism, high serum levels of free T4 (24.2 pmol/L), free T3 (11.7 pmol/L), and sex hormone-binding globulin (157 nmol/L) as well as measurable (by immunofluorometric assay) serum TSH concentrations (1.9 mU/L) in the absence of any known methodological interference. The above finding indicated the presence of hyperthyroidism due to inappropriate secretion of TSH, whose neoplastic origin was documented by computed tomographic scan showing a 1-cm pituitary adenoma. The diagnosis was confirmed by elevated alpha-subunit levels (9.2 micrograms/L) and alpha-subunit/TSH molar ratio (25.2) as well as absent TSH suppression after T3 administration. TRH injection (200 microgram, iv) caused impaired TSH (from 3.0 to 4.8 mU/L) and unexpectedly exaggerated alpha-subunit (from 8.8 to 18.2 micrograms/L) responses. Such a discrepancy was also observed after other dynamic tests. Double gold particle immunostaining of the adenomatous tissue removed at surgery showed that all of the cells contained secretory granules positive for alpha-subunit, while very few cells were positive for TSH beta and alpha-subunit. In conclusion, the present study demonstrates the existence of TSH-induced hyperthyroidism due to a pituitary adenoma composed of two different cell types: one secreting alpha-subunit alone and another cosecreting alpha-subunit and TSH.

Adenoma↗
PubMed1991

Exogenous melatonin enhances the TRH-induced prolactin release in normally cycling women: a sex-specific effect.

The aim of the present study was to analyze the effects of exogenous melatonin (MT) upon pituitary and adrenal responsiveness to releasing hormones in different phases of the menstrual cycle. We evaluated the response of FSH and LH to 100 micrograms gonadotropin releasing hormone, of TSH and prolactin (PRL) to 200 micrograms thyrotropin releasing hormone (TRH), and of cortisol to 10 micrograms ACTH 1-17. We studied eight young women with normal ovulatory cycles in the early follicular (days 5-7) and luteal (days 22-24) phases. Stimulation tests were performed at 18.00 in baseline conditions as well as 1 h after oral intake of exogenous MT (2 mg as a gelatine capsule). We did not observe any significant change in FSH, LH, TSH and cortisol responses to their respective releasing hormones in either phase of the cycle. PRL response to TRH was higher after MT in the follicular phase, when evaluated in terms of net increment and integrated area of response (p less than 0.02 versus baseline conditions for both variables). In the luteal phase, we recorded larger interindividual variability and higher responses after MT were observed in five out of eight subjects. These results suggest that MT may play a facilitatory role in the TRH-induced PRL release in women of reproductive age.

Adrenal Glands↗
PubMed1991

[Mycoses and adrenocortical function. New pathogenetic aspects of adrenal hypofunction].

Three aspects of the possible relationships between adrenocortical function and mycoses are considered: a) abnormal steroid hormone concentrations that may favour onset and/or clinical course of mycotic diseases; b) presence of granulomas in the adrenal glands during systemic mycoses; c) effects of antifungal drugs on steroidogenesis. Glucocorticoids are potent inhibitors of T-lymphocyte proliferation, in that they affect both the production of IL-1 from monocytes/macrophages and IL-2 from activated T-lymphocytes. Consequently opportunistic fungal infections are frequently observed in patients with chronic hypercortisolism (Cushing's syndrome) and in particular in those under chronic treatment with corticoids. On the other hand, mucocutaneous candidiasis is a prominent feature of the autoimmune polyglandular syndrome type I, characterized by adrenal insufficiency, hypoparathyroidism and mucocutaneous candidiasis. Its onset is usually at childhood, first with symptoms and signs of the fungal infection and then with those of endocrine failure. It is a complex disorder, familiar or sporadic, not linked to particular HLA haplotype, potentially associated with other autoimmune diseases (endocrine and not), thus forming the so called candidiasis endocrinopathy syndrome (CES). Adrenal involvement is very frequent in systemic mycoses, such as histoplasmosis (Histoplasma capsulatum), cryptococcosis (Cryptococcus neoformans), and paracoccidioidomycosis. From the pathogenetic view point, corticostatins-defensins may play a role. They are a family of recently discovered cationic peptides, that are able to inhibit adrenal steroidogenesis by interfering with ACTH at the specific receptor level. The pharmacological effects of ketoconazole on adrenal (and gonadal) steroidogenesis are a focus of great interest. This compound has been demonstrated to be a potent inhibitor of cytochrome P450-dependent enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Drugs and andrological side-effects].

Human sexual behaviour is determined by different regulatory systems. Central and peripheral nervous system, endocrine and vascular systems, all play a pivotal role in the modulation of male sexual activity. Therefore, many steps of possible drug interference can be recognized. In this regard, drugs are usually classified on the basis of their side effects (impairment of libido, erection and/or ejaculation). In the present work we review the sexual-related side effects of drugs of widespread clinical use on the basis of their mechanism and site of action.

Central Nervous System↗
PubMed1990

Melatonin and human cancer.

A number of studies performed in vitro and on experimental animals supported the view that pineal gland inhibits neoplastic growth. Data in humans are scanty and controversial. In the present study we measured serum melatonin (MT), prolactin (PRL) and growth hormone (GH) concentrations, at 08.00 and 24.00, in 132 cancer patients and in 58 healthy control subjects. The patients were stratified according to histology and stage of disease as follows: 30 stage I-II and 45 stage III-IV breast cancer (BC); 39 stage III-IV lung cancer; 18 advanced gastrointestinal (GI) cancer. We also measured MT levels, at the same time-points, in 20 women with primary BC before and after radical mastectomy. Finally, we evaluated the circadian rhythm of serum MT in 18 patients with advanced cancer. On the whole, the patients with advanced tumors showed serum MT levels significantly higher than controls, without any correlation with PRL and GH values. When looking at stage III-IV vs stage I-II BC patients, significantly higher MT levels have been found in the former group. The surgical removal of the primary BC was not associated with any changes in MT values at both time points considered. A highly significant rhythm of serum MT was recorded in advanced cancer patients and the rhythmic parameters were substantially superimposable on those of the control subjects.

Adult↗
PubMed1990

Morning to evening changes of human pituitary and adrenal responses to specific stimuli.

We performed a combined stimulation test with the simultaneous application of GnRH (100 micrograms), TRH (200 micrograms) and ACTH (10 micrograms) in 10 healthy adult males at two opposite clock timing, i.e. at 09:00 and 21:00 h. Pituitary (gonadotropins, PRL, TSH) and adrenal (cortisol, aldosterone, progesterone) hormones showed a common trend of enhanced responsiveness to the evening challenge. Differences reached statistical significance in the case of cortisol, aldosterone, PRL and FSH. These findings suggest that the responsiveness of some pituitary and adrenocortical hormones to specific stimuli is physiologically different in humans as a function of the clock timing, being higher in the evening than in the morning. From the clinical standpoint, however, differences in the magnitude of responses were not enough to recommend provocative testing at a particular clock time, at least for routine diagnostic purposes.

Adrenal Glands↗
PubMed1990

Levels of eighteen non-conjugated and conjugated steroids in human breast cyst fluid: relationships with cyst type.

The present study investigates the levels of a large series of 18 non-conjugated or conjugated steroids in 71 samples of human breast cyst fluid (BCF) as divided into three groups corresponding to different electrolyte composition. In the type 1 group, the K+/Na+ ratio was higher than 1.5, while in type 2 it was lower than 0.66 and finally type 3 had an intermediate ratio. Pregnenolone (PREG) and progesterone (PROG) levels were approximately 2-fold higher (P less than 0.05) in the type 2 than in the type 1 group while both 17-OH-pregnenolone (17-OH-PREG) and 17-OH-progesterone (17-OH-PROG) concentrations were similar in these two groups. Most of the C-19 steroids analyzed, namely dehydroepiandrosterone sulfate (DHEAS), androst-5-ene-3 beta, 17 beta-diol (5-ene-DIOL), testosterone (TESTO), dihydrotestosterone (DHT), androstane-3 alpha, 17 beta-diol (3 alpha-DIOL), androsterone (ADT), androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-DIOL-G) and androsterone glucuronide (ADT-G) were 180-360% (P less than 0.05) higher in type 1 than in type 2 cysts while no difference in C-18 steroid and C-18 steroid glucuronide levels was observed. A small or no difference was seen in steroid levels between types 2 and 3. We conclude that the arbitrary division according to the electrolyte composition of BCF permits identification of different patterns of steroid concentrations in BCF. However, the mechanism responsible for both sets of parameters remain unclear.

Adult↗
PubMed1990

Effects of long-term, low-dose, time-specified melatonin administration on endocrine and cardiovascular variables in adult men.

Six healthy adult male volunteers underwent serial blood drawings at 4-hour intervals over 24 hours for the definition of melatonin (MT), prolactin (PRL), cortisol, and testosterone circadian patterns. Serum levels of triiodotironine (T3) and thyroxine (T4) were determined at 0800. Systolic and diastolic blood pressure and heart rate were automatically recorded every 30 minutes for 24 hours. The responses of luteinizing hormone (LH), follicle stimulating hormone (FSH), PRL, thyroid stimulating hormone (TSH), cortisol, and aldosterone to a stimulation test with gonadotrophin-releasing hormone (Gn-RH), thyrotrophin-releasing hormone (TRH), adrenocorticotrophin (ACTH), and testosterone to human chorionic gonadotrophin (HCG) were also evaluated. The same protocol was repeated after a two-month course of treatment with MT, 2 mg per os daily at 1800. After treatment, we recorded a marked elevation of mean serum MT levels with a significant phase-advance of its circadian rhythm. The 24-hour patterns of cortisol and testosterone displayed an anticipation of the morning acrophase of about 1.5 hour (not significant) for cortisol and three hours (P less than 0.05) for testosterone. PRL pattern was unchanged as well as serum levels of thyroid hormones. The circadian organization of the cardiovascular variables did not show any changes after MT supplementation; the pituitary, adrenal, and testicular responses to specific stimuli were comparable before and after treatment. These results are compatible with the view that the MT signal may provide temporal cues to the neuroendocrine network for the organization of testicular circadian periodicity.

Adrenocorticotropic Hormone↗
PubMed1990

Unconjugated and glucuronide steroid levels in human breast cyst fluid.

The present report deals with the concentrations of C-21, C-19 and C-18 steroids as well as steroid glucuronides, namely androstane-3 alpha,17 beta-diol glucuronide, androsterone glucuronide, estradiol glucuronide, and estrone glucuronide (E1-G) in breast cyst fluid (BCF). The concentration of the gross breast cystic disease protein 15 (GCDFP-15) was also measured and its value was correlated with concentrations of unconjugated steroids as well as steroid conjugates. The present data indicate that for a large number of unconjugated steroids (namely pregnenolone, progesterone, dehydroepiandrosterone (DHEA), androsterone, androstane-3 alpha,17 beta-diol, estrone and estradiol) there is an important accumulation in BCF. Our data permit us to demonstrate a statistical relationship between the concentrations of DHEA and its metabolites (namely, androstenedione [4-ene-Dione]), thus suggesting an activity of the enzyme 3 beta-hydroxysteroid dehydrogenase-4-ene-5-ene-isomerase in the breast tissue. Further examination of the relationship between the concentrations of 4-ene-Dione and its metabolites, namely testosterone and 5 alpha-reduced steroid metabolites, as well as their glucuronide derivatives, strongly suggests that the metabolism of androgens in the breast tissue occurs mainly via 5 alpha-reductase and glucuronyl transferase activities. The concentration of GCDFP-15 in BCF found in the present investigation was 2745 +/- 234 micrograms/ml and we have shown that a negative relationship exists in the BCF between E1-G and GCDFP-15 levels.

Exudates and Transudates↗