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Biomedical subjects

C Flamigni

Publications and source records attributed to C Flamigni.

At least 127 records · Page 7Linked to original sources

Ketoconazole therapy for women with acne and/or hirsutism.

The effects of ketoconazole, a synthetic imidazole derivate, were evaluated in 42 women affected by acne (17 cases) and/or hirsutism (36 cases) treated with 400 mg/day for 3-6 months. Androstenedione, total and free testosterone, 5 alpha dihydrotestosterone and dehydroepiandrosterone levels progressively dropped during treatment while 17 alpha hydroxyprogesterone, estradiol, ACTH, cortisol, LH and FSH levels increased. Dehydroepiandrosterone sulfate decreased only towards the end of treatment, while estrone, sex hormone binding globulin, and PRL remained unchanged. Daily mean +/- SD rate of hair growth, measured by a special image analysis processor, decreased within 3 months of therapy from 0.258 +/- 0.058 to 0.184 +/- 0.039 mm/day (P less than 0.02) and mean +/- SD hair diameter from 0.123 +/- 0.015 to 0.110 +/- 0.013 mm (P less than 0.05) together with decreasing hormone levels. The therapeutic effects of ketoconazole on hirsutism was evident at 6 months in only 14 subjects, while no significant change in hirsutism score was recorded in 22 women who failed to complete the therapy. Acne improved in all cases. Several side effects and complications arose during treatment, such as headache, nausea, loss of scalp hair, hepatitis, and biochemical changes. Even though ketoconazole improves hyperandrogenism, only selected patients are eligible for treatment as scrupulous monitoring is required.

Acne Vulgaris↗

Endocrine and ovarian parameters at various frequencies of ovulation in adolescents.

We assessed ovarian and endocrine function in 86 adolescents over a six month period. Postmenstrual estrone (E1) and estradiol-17 beta (E2) levels, premenstrual FSH levels and pre- and postmenstrual LH, testosterone (T) and androstenedione (A) levels decreased as the frequency of ovulation increased, while premenstrual E2, progesterone (P) and 17 alpha-hydroxyprogesterone levels increased. Both right and left ovarian volume and the per cent of multifollicular ovaries decreased with an increase in the frequency of ovulation. In the premenstrual phase P values correlated significantly with frequency of ovulation for FSH (r = -0.43: P less than 0.001), LH (r = -0.36: P less than 0.01), T (r = -0.31: P less than 0.05) and A (r = -0.26: P less than 0.05). Our data suggest that in the postmenarcheal period the progressive loss of immature endocrine and ovarian characteristics (high LH, FSH, and androgen levels and enlarged, multifollicular ovaries) is linked to an increasing number of ovulations. Progesterone plays a major role in the development of cyclic function characteristic of adult maturity.

17-alpha-Hydroxyprogesterone↗

Uterine development and endocrine relationships after menarche.

Uterine volume and ovarian/uterine ratio during the first 6 postmenarchal years in 143 women were compared with an adult control group. Plasma gonadotropins and sex steroids were also correlated with uterine volume in adolescents. Uterine volume increased progressively and correlated positively with advancing postmenarchal (r = 0.24; p less than 0.05) and chronologic (r = 0.23; p less than 0.05) age. However, normal adult uterine volume was not yet reached by the highest postmenarchal (6 years) and chronologic (18 years) age. The ovarian/uterine ratio decreased gradually with increasing postmenarchal age but was always higher (0.22) than that of control subjects (0.12). Uterine volume correlated positively with plasma estradiol (r = 0.25; p less than 0.05) and dehydroepiandrosterone (r = 0.22; p less than 0.05) and its sulfate (r = 0.22; p less than 0.05) levels. This study indicates that the uterus continues to grow after menarche in conjunction with increasing hormone levels.

Adolescent↗

Gaze and eye-contact with anorexic adolescents.

Interviews with seven anorexic female adolescents and 12 control subjects were videotaped for analysis of visual behaviour. Individual looking and mutual gaze of subject and interviewer were coded by two judges and recorded through a two-channel push-button system of time recording for 10 min of interview segments. The results indicated that anorexics looked toward the eyes of the interviewer less frequently and more briefly than controls, and that mutual gazing was less common.

Adolescent↗

Evidence for a specific role of GnRH pulse frequency in the control of the human menstrual cycle.

An adequate frequency of gonadotropin-releasing hormone (GnRH) pulses appears to be important for physiological gonadotropin secretion. However, limited information exists on the exact role of this parameter in the regulation of the human menstrual cycle. Thus we studied gonadotropin and gonadal steroid secretion in 32 women with primary hypogonadotropic amenorrhea who received pulsatile GnRH (60 to 120 micrograms/day) at 60- or 120-min intervals for a total of 64 ovulation induction cycles. Ovulation was achieved in 94% of 60-min and in 70% of 120-min cycles P less than 0.05). In the follicular phase of ovulatory cycles, estradiol (E2) levels did not differ among the four groups; however, mean luteinizing hormone (LH) levels were lower (P less than 0.005), and the midcycle LH surge was severely blunted in cycles of subjects receiving 120 micrograms/day (5 micrograms/bolus) GnRH every 120 min compared with subjects receiving the same dose of GnRH per day or per bolus every 60 min. Luteal progesterone (only in 60 micrograms/day GnRH cycles) and E2 levels were lower in 120-min than in 60-min cycles (P less than 0.05). The use of the higher daily GnRH dose (120 micrograms/day) reduced or abolished the frequency-associated hormone level differences. We conclude that a low frequency of pulsatile GnRH in women 1) decreases mean LH levels and blunts the midcycle gonadotropin surge, 2) does not increase follicle-stimulating hormone concentrations, and 3) is associated with a reduced rate of ovulation.

Adult↗

High concentrations of catecholamines in human hypothalamic-hypophysial blood.

While the hypothalamic-hypophysial portal system has been extensively studied in laboratory animals, equivalent studies have not been performed in humans. Here, we present an experimental procedure for collecting suprapituitary blood in man. To solve the question on the origin of such blood we investigated specific markers of hypothalamic secretory activity: the catecholamines (CAs). We found (a) norepinephrine (NE), dopamine (DA), and epinephrine (E) concentrations from approximately 1.5 to 2.5, 3.5 to 4.5, and 6- to 10-fold higher, respectively, in suprapituitary than peripheral blood, (b) different NE/DA and NE/E ratios in favor of DA and E in suprapituitary blood, and (c), a complete (100%) group separation (suprapituitary vs. peripheral) when discriminant analysis included only DA and E. These data indicate that suprapituitary blood composition is different from that of the peripheral blood, and is particularly rich in CAs and claimed differences between DA and E release on one hand and NE release on the other in suprapituitary blood also are observed. We advance the hypothesis of a hypothalamic source of such amines draining via median eminence into portal vasculature, and name this blood "hypothalamic-hypophysial blood." Besides serving as "classical" neurotransmitters, CAs may also have a direct neurohormonal role in the regulation of the human hypothalamic-hypophysial function.

Adult↗

The abnormal response of polycystic ovarian disease patients to exogenous pulsatile gonadotropin-releasing hormone: characterization and management.

Pulsatile GnRH administration for induction of ovulation is often ineffective in polycystic ovarian disease (PCOD) patients. To clarify and correct the endocrine mechanisms underlying this deranged response we gave pulsatile GnRH (5 micrograms, iv, every 60 min) to idiopathic hypogonadotropic hypogonadism (IHH) patients with primary amenorrhea for 19 cycles and to PCOD patients for 24 cycles before (pre-A) and for 25 cycles after (post-A) GnRH analog suppression. Compared to IHH, pre-A cycles were characterized by elevated LH, estradiol, and testosterone; reduced luteal phase progesterone; and low ovulatory (38%) and pregnancy rates (8%). Conversely, LH, estradiol, and follicular phase testosterone levels were lower in post-A than in pre-A cycles, while luteal phase progesterone was higher; the endocrine pattern of post-A cycles closely resembled the one of IHH cycles. The ovulatory and pregnancy rates of PCOD patients improved remarkably in post-A cycles (90% and 38%, respectively). Excessive body weight was associated with a lower incidence of ovulation in both pre-A (15%) and post-A cycles (75%). A worse endocrine pattern and a lower ovulatory rate (50%) were obtained when a second consecutive post-A cycle occurred without repeating GnRH analog suppression. No signs of even mild ovarian hyperstimulation and no multiple pregnancies were recorded in the post-A cycles. We conclude that in PCOD 1) deranged pituitary sensitivity, excessive ovarian androgen secretion, and obesity critically affect folliculogenesis and ovulation; 2) pituitary-gonadal suppression with a GnRH analog markedly improves the endocrine and clinical responses to pulsatile GnRH ovulation induction; 3) optimal results can be achieved only when each pulsatile GnRH cycle is preceded by GnRH analog suppression; and 4) pulsatile GnRH is highly effective and safe for ovulation induction, provided that PCOD subjects are pretreated with a GnRH analog.

Adult↗

[Controlled clinical study of cyclopyroxolamine in vaginal candidiasis].

The clinical and microbiological results of the treatment of vulvovaginal candidiasis with cyclopyroxolamine or miconazole in thirty-eight patients are discussed. Cyclopyroxolamine treatment was demonstrated to be an effective and well-tolerated compound for the treatment of this kind of infection.

Adult↗

Basement membrane components in normal hyperplastic and neoplastic endometrium.

The major basement membrane (BM) components, laminin and type IV collagen, were studied by immunochemistry in normal, hyperplastic, and neoplastic endometrium. By immunoperoxidase technique, proliferative and secretive endometrium showed capillary and epithelial cell basement membranes with linear staining with antibodies to both laminin and type IV collagen. Immunostaining of laminin and type IV collagen showed that capillaries were surrounded by a continuous perivascular sheath of these matrices in specimens of adenomatous hyperplasia and in nearly all specimens of endometrial adenocarcinoma. Laminin and type IV collagen were found to accumulate around glandular epithelial cells of adenomatous hyperplastic endometrium, but in several specimens these linear surrounding formations were defective and discontinuous. In several areas of well-differentiated endometrial adenocarcinomas BM-like structures were found around glandular epithelial cells as shadows without staining for laminin and type IV collagen. These basement membrane components accumulate around stromal cells to encircle each cell with a gradual, progressive, and cyclic process depending on the phase of the menstrual cycle. Laminin and type IV collagen were clearly detected around stromal cells at days 20 to 22 of the menstrual cycle and more thickly at days 26 to 28. The accumulation of these matrices around stromal cells is a progesterone/progestin-related process. In the well-differentiated adenocarcinoma a mid-term treatment with progestin (Danatrol Maggioni-Winthrop, SPA, Milan, Italy) was found to be effective on laminin and type IV collagen accumulation around stromal cells.

Adenocarcinoma↗

Biological and endocrine aspects of transdermal 17 beta-oestradiol administration in post-menopausal women.

The plasma protein distribution of oestradiol (E2) and oestrone (E1) during transdermal E2 administration (100 micrograms/24 hr) was studied in 12 post-menopausal women. The E2 and E1 levels observed were 43-83 pg/ml and 37-73 pg/ml, respectively. The levels of the free, albumin-bound and sex-hormone-binding globulin (SHBG) bound fractions were in the ranges 1.4-1.9%, 60-65% and 35-45%, respectively, in the case of E2, and 2.8-3.0%, 80-89% and 15-20%, respectively, in that of E1. The SHBG levels also remained unaltered. It was concluded that transdermal administration of E2 at the dosage employed produces a physiological plasma protein distribution of E2 and E1 and does not affect liver protein production.

Administration, Cutaneous↗

Extraction of estrogens by human perfused uterus. Effects of membrane permeability and binding by serum proteins on differential influx into endometrium and myometrium.

The present study was undertaken to examine the extractions of estradiol, estrone, and estrone sulfate from the circulation of the human perfused uterus. The differential permeability of endometrial and myometrial vascular beds to estrogens was evaluated in uteri samples obtained during the proliferative and secretive phases of the menstrual cycle. The effects of binding by human serum proteins on estrogen influx into the endometrium and myometrium were also determined by the use of double-isotope, single-injection, timed tissue sampling techniques adapted to the extracorporeal perfusion of human uterus. Tritiated test estrogen was injected into the uterine artery as a mixture with 14C-butanol, a free diffusible reference substance. The influx of 14C-dextran (a membrane-impermeable compound) was used to test the aspecific influx from vasculature to extravascular space. Results show that in the human perfused uterus: (1) membrane permeability plays different roles in estrogen influxes between the endometrium and myometrium; (2) during the proliferative and secretive phase of the menstrual cycle the uterine microvessels are differently permeable to the free plus protein-bound estrogens; and (3) plasma proteins decrease the endometrial and myometrial uptakes of estrogens.

Blood Proteins↗

Early human pregnancy in vitro utilizing an artificially perfused uterus.

The penetration of luminal epithelium in the uterine cavity represents the crucial event that triggers the failure of embryo implant, thus limiting the possibility of fertility control. The purpose of our study was to implant a human blastocyst, cultured in vitro, into a human uterus extracorporeally perfused with an oxygenated medium. For this purpose, human blastocysts, collected from patients who underwent IVF program because of irreparable tubal infertility, were injected under the luminal epithelium of human perfused uteri. Light and electron microscopy showed that human blastocyst can successfully undergo the stage of implantation and trophoblastic invasion in 52 hours of extracorporeal perfusion.

Blastocyst↗

Episodic pulsatile secretion of FSH, LH, prolactin, oestradiol, oestrone, and LH circadian variations in polycystic ovary syndrome.

Pulsatile secretion of LH, FSH, PRL, oestradiol and oestrone was studied in a group of 16 patients with micropolycystic ovary syndrome (PCOS) and compared with that of normal ovulatory women in the fifth to sixth day of the cycle. Hormone concentrations were measured at 10 min intervals for 8 h starting at 0930 h. In seven subjects, the study was prolonged for 24 h, with 20 min interval samples, in an attempt to evaluate the circadian rhythm of LH by cosinor analysis. Significant fluctuations occurred in the concentration of each hormone. Values shown are mean +/- SD. PCOS subjects had high LH mean values (27.9 +/- 5.9 IU/l) (P less than 0.005). LH pulse amplitude was higher than controls (11.6 +/- 3.7 IU/l versus 5.2 +/- 1.8 IU/l; P less than 0.005) while no consistent changes in frequency or interpulse interval (62.0 +/- 10.7 min versus 65.8 +/- 19.2 min; P = NS) were found. A mean of 4.8 +/- 1.2 pulses of FSH occurred in 8 h and the mean pulse amplitude was 2.68 +/- 1.11 with no differences from controls. All patients were normoprolactinaemic. A mean of 5.5 +/- 1.9 pulses occurred in 8 h, the interpulse interval was 76.1 +/- 14.4 min and the amplitude was 2.87 +/- 0.76 ng/ml and there were no significant differences from controls; 75% of PRL pulses showed a temporal relationship with LH pulses. Oestrone mean basal values were higher in PCOS (47.2 +/- 12.5 pg/ml) than controls (32.0 +/- 9.9 pg/ml; P less than 0.02), while no differences were observed as regards oestradiol. Oestradiol pulse amplitude was nearly the same as oestrone (43.6 +/- 18.8 pg/ml and 37.7 +/- 16.1 pg/ml, respectively); 6.0 +/- 2.2 pulses and 6.0 +/- 1.6 pulses occurred in 8 h with an interpulse interval of 81.1 +/- 27.1 min and 71.8 +/- 11.1 min, respectively. Sixty-five per cent of LH pulses were followed by an oestradiol and oestrone peak. The mean time of the appearance was 17 +/- 15 min and 25 +/- 23 min, respectively. In the PCOS group a consistent 24 h rhythm in mean plasma LH levels was found with the highest hormone values at 1720 h (P less than 0.05) unrelated to apparent sleep and different from that of adult women. Pulse frequency showed a significant slowing during the night with the longest interpulse interval at 0327 h (P less than 0.03) while no significant periodicity was observed in LH pulse amplitude.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Evidence for a hypothalamic alteration of catecholamine metabolism in polycystic ovary syndrome.

The role of brain catecholamine (CA) activity in the neuroendocrine regulation of the GnRH-LH system in polycystic ovary syndrome (PCO) was investigated by high-performance liquid chromatography (HPLC) with electrochemical detector. We measured urinary dopamine (DA), noradrenaline (NA), adrenaline (A), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and total 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in a group of 12 women with PCO before and during peripheral dopa-decarboxylase blockade, by carbidopa. HVA and DOPAC concentrations were significantly lower (P less than 0.001 and P less than 0.005, respectively) in PCO patients compared with twelve control subjects in early follicular phase, whereas total MHPG concentrations and MHPG/VMA ratio were significantly higher (P less than 0.005) in PCO patients. Moreover, HVA and DOPAC concentrations in PCO patients were similar to those of the control subjects in preovulatory phase, while MHPG concentrations remained higher in PCO patients (P less than 0.01). DA, NA, A and VMA concentrations were similar to those of control subjects in both phases of the cycle. During carbidopa administration the concentrations of all urinary CAs and metabolites were unchanged, except those of DA which dropped markedly (P less than 0.001). These data suggest that (1) an altered central catecholamine metabolism consisting of DA deficiency and NA excess is present in PCO, and (2) the site of DA deficiency may be located in the hypothalamus.

3,4-Dihydroxyphenylacetic Acid↗

Gonadotropin-releasing hormone (GnRH) analog suppression renders polycystic ovarian disease patients more susceptible to ovulation induction with pulsatile GnRH.

Pulsatile GnRH administration consistently restores normal reproductive hormone levels and ovulation in women with hypogonadotropic hypogonadism, but is less effective in those with polycystic ovarian disease (PCOD). We pharmacologically created a hypogonadotropic condition with a GnRH analog (GnRH-A) in six women with PCOD to investigate the role of deranged gonadotropin secretion in PCOD and to improve the response to pulsatile GnRH ovulation induction. Before GnRH and GnRH-A treatment the women with PCOD had increased LH pulse frequency [one pulse every 55 +/- 2 (+/- SE) min; P less than 0.05] and LH pulse amplitude (10.9 +/- 1.4 U/L; P less than 0.05) compared to normal women in the follicular phase of their menstrual cycle. Each PCOD woman completed one cycle of pulsatile GnRH administration for ovulation induction before (pre-A cycles; n = 6) and one or two cycles after (post-A cycles; n = 9) GnRH-A administration [D-Ser(tBu)6-Des,Gly10-GnRH; 300 micrograms, sc, twice daily for 8 weeks]. Pulsatile GnRH (5 micrograms/bolus) was given at 60-min intervals using a Zyklomat pump. Daily blood samples were drawn during the pulsatile GnRH ovulation induction cycles for the determination of serum LH, FSH, estradiol (E2), progesterone, and testosterone, and pelvic ultrasonography was done at 1- to 4-day intervals. Mean (+/- SE) serum LH levels were elevated during the pre-A cycle (49.2 +/- 3.1 IU/L) and decreased to normal levels during the post-A cycles (19.6 +/- 1.4 IU/L; P less than 0.0001). Mean testosterone concentrations were lower during the post-A cycles [88 +/- 2 ng/dL (3.1 +/- 0.1 nmol/L)] than during the pre-A cycles [122 +/- 3 ng/dL (4.2 +/- 0.1 nmol/L); P less than 0.0001]. In the follicular phase of the post-A cycles E2 levels were significantly lower [81 +/- 5 pg/mL (300 +/- 20 pmol/L) vs. 133 +/- 14 pg/mL (490 +/- 50 pmol/L); P less than 0.0001], preovulatory ovarian volume was smaller (24.6 +/- 2.0 vs. 31.4 +/- 2.4 cm3; P less than 0.01), and the FSH to LH ratio was higher (0.56 +/- 0.03 vs. 0.16 +/- 0.01) than in the pre-A cycle, suggesting more appropriate function of the pituitary-gonadal axis. Excessive LH and E2 responses to pulsatile GnRH administration in the early follicular phase of the pre-A cycle were abolished in the post-A cycles.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

GnRH agonists and antagonists. Current clinical status.

Gonadotrophin-releasing hormone (GnRH) analogues offer a novel approach for the non-steroidal manipulation of the reproductive endocrine axis. GnRH agonists are now effectively employed in the management of precocious puberty, prostate and breast cancer, endometriosis, uterine leiomyoma, polycystic ovarian disease, and various other disorders. Unfortunately, contraceptive applications of GnRH agonists have been disappointing. The availability of slow release depot formulations of GnRH agonists, and the development of GnRH antagonists may further optimise and extend the clinical application of these compounds.

Humans↗