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Two new low-lying $^6$He levels at excitation energies of about 2.4 and 2.9 MeV were observed in the experimental investigation of the p-$\alpha$ coincidence spectra obtained by the $^3$H($^4$He,p$\alpha$)2n four-body reaction at $E_{\rm \,^4He}$ beam energy of 27.2 MeV. The relevant $E^*$ peak energy and $\Gamma$ energy width spectroscopic parameters for such $^6$He$^*$ excited states decaying into the $\alpha$+n+n channel were obtained by analyzing the bidimensional ($E_{\rm p}$, $E_{\rm \alpha}$) energy spectra. The present new result of two low-lying $^6$He$^*$ excited states above the $^4$He+2n threshold energy of 0.974 MeV is important for the investigation of the nuclear structure of neutron rich light nuclei and also as a basic test for theoretical models in the study of the three-cluster resonance feature of $^6$He., Comment: 16 pages, 7 figures, 2 tables, accepted for publication in Mod. Phys. Lett. A

The dynamical fusion process of 48Ca + 144Sm with different impact parameters near barrier is studied by an extended quantum molecular dynamics (EQMD) model, where width of wavepacket is dynamically treated based on variational principle. The time evolution of different energy components such as potential energy, kinetic energy, Coulomb energy and Pauli potential are analyzed when dynamical or fixed width is assumed in calculation. It is found that the dynamical wavepacket width can enhance the dissipation of incident energy and the fluctuations, which are important to form compound nuclei. Moreover, we compare the fusion barrier dependence on the incident energy when it is determined by both dynamical and fixed wavepacket width.

The effects of physiological changes in estrogens and androgens on the erythrocyte antioxidant superoxide dismutase, catalase and glutathione peroxidase enzyme activities during the menstrual cycle were investigated in healthy eumenorrheic women. Blood samples were taken on alternate days from twelve normally cyclic women (age range: 20 to 27 years; mean age: 24.1 years) from the first day of one menstrual cycle until the first day of the subsequent one. Plasma was analyzed for FSH, LH, estradiol, progesterone, testosterone, free testosterone and androstenedione concentrations. Erythrocyte superoxide dismutase, catalase and glutathione peroxidase activities were evaluated on the same days and cycle length was standardized on the basis of the preovulatory estradiol peak. Significant cyclic phase-related changes were observed in glutathione peroxidase (P

Bone mineral density (BMD) measured by densitometry is the elective parameter for the diagnosis of osteopenia and osteoporosis. Biochemical markers have been proposed as sensitive indicators of high bone turnover and for monitoring response to antiresorptive treatment. We conducted a retrospective study to investigate the values of biochemical markers of bone metabolism with a view to early diagnosis of osteoporosis and monitoring of hormone replacement and calcitonin therapy. The subjects were 415 women, mean age 51+/-8 years (43-62 years) in peri- and postmenopause, recruited at the Menopause Center of Obstetrics and Gynecology Department of Siena University and divided in five groups. Bone densitometry was performed in all subjects and blood samples were taken for assayed biochemical markers, that is, [osteocalcin (OC), parathyroid hormone (PTH), type 1 procollagen (PICP), and calcitonin (CT)]. Three groups of women were divided into two subgroups: those with normal and those with low BMD (1 SD). Basal concentrations of PCP1, OC, PTH, and CT were compared in the various groups. Two groups of postmenopausal women with BMD below the normal were treated with estrogen replacement therapy and unmodified eel calcitonin. We evaluated whether some of these biochemical markers of bone turnover could help identify women with low BMD and whether they could be useful for monitoring the results of antiresorptive therapies. Markers of bone formation (PICP and OC) make it possible to distinguish women with high turnover who are at risk for osteoporosis from women with low turnover in menopause. A good correlation was also found between changes in levels of these markers and changes in BMD during treatments, which suggests that the PICP and OC would be useful for monitoring response to antiresorptive therapy.

This paper reports a case of factor VII deficiency, a very rare autosomal recessive disorder, in a primipara at 37 weeks of gestation in whom we administered prophylactic therapy with factor VII every 12 h until 24 h after delivery. The prophylactic use of factor VII enabled the woman to deliver without hemorrhagic complications.

Anxiety is one of the main symptoms in menopause. The aim of this study was to evaluate the efficacy of the association of Kava-Kava extracts with hormone replacement therapy (HRT) and to compare it with HRT alone in the treatment of postmenopausal anxiety.Forty women in physiological or surgical menopause for the past 1 to 12 years were enrolled in the study. Patients in physiological menopause were randomly assigned to one of the following protocols: TTS natural estrogens 50 micrograms/day with progestin and Kava-Kava extract at a dose of 100 mg (HRT + K, no. = 13); TTS natural estrogens 50 micrograms/day with progestin and a placebo product (HRT, no. = 9). Patients in surgical menopause were randomly assigned to one of the following protocols: TTS natural estrogens 50 micrograms/day and Kava-Kava extract at a dose of 100 mg (ERT + K, no. = 11); TTS natural estrogens 50 micrograms/day and a placebo product (ERT, no. = 7). Each treatment cycle lasted for 6 months. The outcome of the study was to evaluate changes in the HAMA score.A significant reduction in the HAMA score was observed after 3 and 6 months' treatment in all four groups of women studied. The groups treated with the therapeutic association (HRT + K, ERT + K) showed a greater reduction in the HAMA score compared to patients in the groups treated with hormones alone.The results of this study show that the association of HRT and Kava-Kava extract may represent an excellent therapeutic tool for the treatment of women in stabilized menopause, in particular those suffering from anxiety and depression, given that Kava-Kava therapy accelerates the resolution of psychological symptoms without diminishing the therapeutic action of estrogens on organic disease, such as osteoporosis and cardiovascular disease.

Tumor-associated trypsin inhibitor (TATI) was assayed in healthy subjects and in women with benign and malignant gynecological diseases. Significantly lower levels were found in boys than in healthy adult subjects. No variations in level were evident over the course of a 24 h period. At a cut-off level of 20 micrograms/l elevated concentrations were found in 42%, 11.4% and 19% of women with ovarian, endometrial and cervical neoplasia, respectively. In patients with ovarian tumors TATI level were elevated both in mucinous and serous tumors. TATI does not seem to be useful for diagnosis of uterine tumors, but could have a specific place in the study and management of ovarian tumors, in which serum concentrations can reach levels 100-200 micrograms/l. In the other gynecological diseases maximum levels of 30-40 micrograms/l were observed.

The most effective therapy for endometriosis is a matter for debate. The aim of the present randomized study was to evaluate the efficacy of low doses of danazol on recurrence of pelvic pain in patients with moderate or severe endometriosis, who had undergone laparoscopic surgery and 6 months of gonadotrophin-releasing hormone analogue (GnRHa) therapy. After surgery, 28 patients with moderate or severe endometriosis underwent therapy for 6 months with GnRHa i.m. every 4 weeks. They were then randomized into two groups: group A (14 subjects) was treated with 100 mg/day danazol for 6 months; group B (14 subjects, control) did not receive any type of therapy. After 12 months of treatment, group A had a significantly (P < 0.01) lower pain score than group B. There was no significant difference between the groups in oestrogen concentrations, bone mineral density or side-effects. The results suggest that low-dose danazol therapy reduces recurrence of pelvic pain in patients with moderate or severe endometriosis, treated surgically, and has few or no metabolic side-effects.

The aim of this study was to evaluate the effects of danazol in reducing the volume of fibromyomas and in the treatment of associated symptoms. Twenty women (34–42 years) with uterine fibromyomas were treated with 400 mg/day of danazol for 4-month periods. The women underwent ultrasound examination to determine their uterine volume at enrollment in the follicular phase and after 2 and 4 months. The examination was repeated by the same sonographer 3 and 6 months after the end of therapy. Blood samples were taken on the same days for LH, FSH, estradiol and progesterone assays. After therapy, fibromyoma volume decreased significantly (p < 0.01) by an average of 23.6 ± 5%. All patients experienced partial or complete relief of symptoms while using danazol. Three and six months after the end of treatment the fibromyoma volume had only increased slightly with respect to the volume at the end of therapy, but was still lower than the starting volume. The present study shows the efficacy of danazol at a dose of 400 mg/day for 4 months in reducing the volume of fibromyomas and associated symptoms. The mechanism by which danazol reduces the volume of fibromyomas may be due to reduced estrogen concentrations and to its antiprogesterone effects on uterine myomas.

Abdominal hysterectomy is the most frequent operation performed by gynecologists. The most commonly used techniques are intrafascial, extrafascial and supracervical hysterectomy; in our department we mainly use the first method. A variant of this technique, because during the operation we use only an Allis clamp, simplifies the operation and maintains certain anatomical relationships between neighbouring pelvic structures.To compare two different surgical techniques between 1/1/1991 and 31/12/95, 262 women were randomized pre-operatively: 133 by the intrafascial technique of Richardson and 129 by the variant hysterectomy technique. The difference between the two techniques (Richardson versus variant hysterectomy technique), as performed in our department, was investigated regarding the clamping of uterine vessels, the resection of uterosacral and cardinal ligament. The two-tailed student test was used for continuous data and chi2 analysis for discrete data.Less blood loss occurred in the variant than in the Richardson group (P0.01) and no intrasurgical complications occurred as compared to one case of ureter lesion in the Richardson group. There were no differences in the number of days of hospitalization. No particular post-surgical complications occurred in the follow-up period, which has now elapsed. After 36 months of follow-up the variant group showed a reduced incidence (not significant) of vaginal vault prolapse. The patients who underwent the variant hysterectomy technique reported better compliance with regard to sexual intercourse and urinary function than the Richardson group.We conclude that the variant hysterectomy technique is as valid as the Richardson technique, giving the surgeon the possibility of maintaining certain anatomical relationships between neighbouring pelvic structures. It also has minor delayed complications.

Objective: To evaluate the role of thyroid hormones in maintaining early pregnancy and to examine the association between thyroid physiological functions and immunological parameters. Methods: Forty-five pregnant women with a clinical diagnosis of threatened abortion and a live fetus and 30 normal pregnant women were included in the study. Blood samples were taken on admission to the hospital. The patients were divided retrospectively into two groups on the basis of outcome: 1) 31 women who did not miscarry (positive outcome) and 2) 14 women who miscarried (negative outcome). Plasma TSH, free triiodothyronine (fT3), free thyroxine (fT4), hCG, immunoglobulin (Ig) G and IgM concentrations and blood counts were determined in each patient. Results: Human chorionic gonadotropin was significantly higher in women who did not abort (39.4 ± 16.9 IU/mL) than in women who miscarried (17.6 ± 14.8 IU/mL, P < .001). Free thyroxine but not fT3 was lower in patients with negative outcome (1.25 ± 0.26 ng/mL compared with 1.98 ± 0.22 ng/mL, P < .001) and IgG and IgM plasma levels were higher (780 ± 500 ng/mL compared with 470 ± 300 ng/mL and 930 ± 400 ng/mL compared with 650 ± 280 ng/mL, respectively, P < .05). Plasma TSH levels were higher in patients with negative outcomes (1.72 ± 0.84 mIU/mL compared to 1.01 ± 0.41 mIU/mL, P < .001). Plasma concentrations of hCG and thyroid hormones were significantly correlated with peripheral blood lymphocyte and neutrophil counts only in the group of women who aborted. Conclusion: Our results indicate that maternal immune response, trophoblast function, and maternal thyroid function are somehow correlated. The presence of low concentrations of hCG and fT4 and high levels of TSH and gamma globulins in women with threatened abortion suggests a negative outcome for the pregnancy.

Menopausal symptoms include hot flushes, insomnia, nocturnal sweating, dizziness, headaches and palpitations. These symptoms reflect adaptation of the body to estrogen deprivation which affects various central neurotransmitters.In this study, the efficacy has been tested of a plant product based on extracts of the leaves of Salvia officinalis (sage) and Medicago sativa (alfalfa) in the treatment of hot flushes in 30 menopausal women with these symptoms.Hot flushes and night sweating completely disappeared in 20 women: four women showed good improvement and the other six showed a reduction in symptoms. GnRH and TRH tests were performed in 8 women to evaluate TSH and Prl responses before and after 3 months of therapy. The plants product induced a significant increase in Prl and TSH response to TRH. Basal levels of estradiol, LH, FSH, Prl and TSH were unchanged.The product seams to have a central slight antidopaminergic action without side effects and is an effective agent in the treatment of menopausal symptoms.

The hypothalamo-pituitary-adrenal (HPA) axis is modulated by sex hormones. Few data exist on the relation between acute estrogen deficit and HPA axis response to corticotropin-releasing hormone (CRH). The effects of a sudden drop in estradiol levels on basal and CRH-stimulated levels of ACTH, cortisol, testosterone, androstenedione and 17-hydroxyprogesterone (17-OHP) were assessed in nine premenopausal women (44-48 years of age), before and after ovariectomy. The CRH test was performed before and 8 days after ovariectomy. A significant reduction in ACTH and adrenal steroids but not in cortisol response to CRH was observed after ovariectomy. The ratio of deltamax androstenedione/17-OHP after CRH stimulation was substantially the same before and after ovariectomy, whereas deltamax 17-OHP/cortisol was significantly lower in ovariectomized women showing increased 21- and 11beta-hydroxylase activity. The results show that the acute estrogen deficit induces changes in the HPA axis characterized by reduced stimulated secretion of ACTH and steroids but normal stimulated cortisol production.

Meson photoproduction is a key tool for the experimental investigation of the nucleon excitation spectrum. To disentangle the specific couplings of resonances, in addition to the rather well measured pion and eta photoproduction channels it is mandatory to obtain information on channels involving strange and vector mesons and higher mass pseudoscalar mesons, and the associated multi-particle final states with both charged and neutral particles. In this respect, the new BGO-OD experiment at the ELSA accelerator of the University of Bonn's Physikalisches Institut provides unique instrumentation. We describe the experiment, present its status and the initial program of measurements.

Uterine fibromyomatosis is a widely recognised and well studied pathology that is found in around 30% of over 35-year-old women. It has been extensively demonstrated that the etiology of fibromyomas is hormone dependent and to date the main pathogenetic role in the development of these benign tumours has largely been attributed to estrogens. Uterine fibromyomas have been found to contain a higher level of estrogen and progesterone receptors than in normal uterus. This suggests an etiopathogenetic role also for progesterone, which is confirmed by the higher mitotic index of myomatous tissue cells in luteal phase. Growth factors also seem to be involved in the origin of uterine fibromyomatosis: concentrations of epidermal growth factor (EGF), insulin like growth factor 1 (IGF-I) and platelet derived growth factor (PDGF AB) are present in myomatous tissues together with their receptors. Recent studies have shown that the administration of an anti-progestin compound, like RU 486, causes a reduction in fibromyoma size. The role of progesterone in promoting uterine growth opens new horizons in the treatment of uterine fibromyomatosis. Treatment with GnRH analogs has proved effective in reducing the size of fibromyomas, even if the problem of their regrowth once treatment has been suspended remains unsolved. The administration of 100 mg of danazol for 6 months after treatment using GnRH analogs reduce fibromyoma rebound growth by around 30%.

The effects of 6 months of hormone replacement therapy by transdermal estradiol patches (0.05 mg/day for 21 days) and oral progestogens (10 mg/day for 10 days) on hypothalamic-pituitary-ovarian function was evaluated in 32 perimenopausal women, aged 42-47 years, with irregular anovulatory cycles and menopausal symptoms. Hormone levels evaluated on the 8th and 24th day of the cycle preceding therapy showed follicle-stimulating hormone (FSH) levels above 15 mIU/ml, estradiol less than 45 pg/ml and progesterone less than 800 pg/ml. During therapy, there was an improvement in menopausal symptoms, a decrease in luteinizing hormone (LH) and FSH levels, an increase in estradiol levels and the transdermal patches were well tolerated. At the end of therapy, 19 women continued to have regular ovulatory cycles with progesterone levels similar to those in luteal phase. FSH and LH concentrations were significantly lower than before therapy. This study shows that hormone replacement therapy not only improves menopausal symptoms but may also restore the hypothalamic-pituitary-ovarian function.

The aim of the present study was to optimize the use of serum procollagen type I carboxy-terminal propeptide (PICP) as a possible marker of postmenopausal-376lted changes of bone metabolism. Postmenopausal (n = 20) and healthy fertile young (n = 4) women were studied after informed consent. The postmenopausal women were subdivided in 4 groups: (1) nontreated; (2) treated with estrogen-progestogen replacement therapy; (3) treated with calcitonin, or (4) with kidney or liver diseases. Blood samples were collected at 15-min time intervals for 4, 6 or 8 h. Serum concentration of PICP was measured by radioimmunoassay, in duplicate at two different dilutions. In postmenopausal women mean +/- SEM serum PICP levels were slightly but nonsignificantly higher than in fertile women. Serum PICP levels in estrogen-progestogen or calcitonin-treated women were significantly lower than in non-treated postmenopausal women. Episodic changes of circulating PICP level were observed in fertile and postmenopausal women. The pulses of serum PICP levels did not show significant differences among the groups of women studied. The present study showed that the measurement of serum PICP levels is a useful marker for investigating the changes of bone metabolism. In particular, low PICP levels in postmenopausal women under steroid hormone or calcitonin treatment in part reflect the changes of bone turnover. The pulses of serum PICP levels during a time interval suggest that collagen metabolism in women undergoes a rapid turnover.

Many studies have shown a physiological reduction in thyroid function with age in animals, and less clearly in humans, with an increase in the incidence of age-dependent clinical and subclinical hypothyroidism. Women are more subject to thyroid dysfunction than men. In postmenopausal women the sudden drop in estrogen levels may affect not only pituitary gonadotropins but also other pituitary hormones directly or indirectly involved in reproductive function. The response of thyrotropin to thyrotropin releasing hormone (TRH) has been shown to decrease with age and basal levels of thyrotropin have been found to be reduced in elderly subjects. In the present study we evaluated the response of thyrotropin to TRH before and after ovariectomy in premenopausal women and during estrogen therapy. The response of thyrotropin to TRH after ovariectomy was significantly less than before. Estrogen replacement therapy restored the thyrotropin response to TRH to pre-ovariectomy levels. This significant decrease in the thyrotropin response to TRH observed in surgical postmenopausal women may be explained by lower endogenous estradiol levels.

Oestrogen plays a role in modulating growth hormone (GH), luteinizing hormone (LH), folliclestimulating hormone (FSH) and osteocalcin secretion in women. Indeed, the postmenopausal period is characterized by changes in plasma GH, LH, FSH and osteocalcin levels. The aim of the present study was to investigate the changes in the secretory patterns of these hormones in postmenopausal women under different therapeutic regimens. A total of 20 subjects took part in the study. They were subdivided into four groups comprising 5 untreated postmenopausal women (time since menopause 1–5 years), 5 postmenopausal women receiving steroid hormone replacement therapy, 5 postmenopausal women receiving salmon calcitonin and 5 fertile women with regular menstrual cycles. Blood samples were collected every 15 min for 4 h and hormone levels were measured by radioimmunoassay. Plasma GH levels fell in the postmenopausal women, but were restored under oestrogen-progestogen treatment. The pulsatile patterns of plasma LH and FSH did not show significant differences in the treated and untreated women. Plasma osteocalcin levels showed episodic fluctuations and mean levels decreased under steroid hormone or calcitonin treatment. No significant correlation was observed between plasma GH and osteocalcin or gonadotrophin levels or body mass index.

Estrogen replacement therapy can counteract all postmenopausal symptoms. While low estrogen doses (0.15-0.30 mg of conjugated estrogens/day) can counteract neurovegetative and psychological symptoms, higher estrogen doses (at least 0.625 mg of conjugated estrogens/day) are required to prevent bone mineral loss in postmenopausal women. However, if contra-indications to high estrogen doses exist, drugs other than estrogens can represent a suitable treatment for postmenopausal osteoporosis both alone or in combination with low estrogen doses. Experimental and clinical data have shown that ipriflavone is effective in the treatment of established postmenopausal osteoporosis. With the purpose of evaluating whether ipriflavone is able to enhance estrogen activity on bone metabolism, 133 postmenopausal women were randomly submitted to the treatment with: (1) placebo; (2) 0.15 mg/day of conjugated estrogens; (3) 0.30 mg/day of conjugated estrogens; (4) 0.15 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone; (5) 0.30 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone. One g/day of calcium supplementation was given to all women. In all subjects bone mineral density was measured before and after 6 and 12 months of treatment at the distal radius by dual-photon absorptiometry. A moderate decrease of bone mineral density was evidenced in women submitted to placebo or to estrogen therapy alone. By contrast, an increase of BMD was measured after 12 months of treatment in the women treated with 0.15 (not significant) or 0.30 mg/day (P < 0.01) of conjugated estrogens associated with ipriflavone. Both dosages of conjugated estrogens were able to induce a significant reduction of neurovegetative symptoms. The increase of bone density obtained with the combination of conjugated estrogens with ipriflavone demonstrates that this combination improves the effects of low estrogen doses on bone mass representing a satisfactory approach in the prevention and treatment of all symptoms related to the climacteric syndrome.

The hypothalamo-pituitary axis in a group of 10 women (17-25 years of age) taking low-dose-estrogen oral contraceptives (20 micrograms ethinylestradiol (EE) + 150 micrograms desogestrel) for at least 6 months was investigated. The subjects underwent the GnRH (50 micrograms) and TRH (200 micrograms) stimulation tests for the evaluation of LH, FSH, Pr1, TSH and GH secretion. In the basal blood sample, E2, P, free T, A and SHBG levels were also determined. An elevation in LH response to GnRH was found, whereas FSH was inhibited. After TRH administration, the Pr1 response was the same in the oral contraceptive cycle as in the pretreatment cycle. Similar results were observed after TSH. Significantly, GH responded to TRH stimulation in the oral contraceptive cycles, but not in the pretreatment cycles. These results show that the new combination of 20 micrograms EE and desogestrel blocks hypothalamic production of GnRH. The different response to GnRH of LH and FSH reveals a differentiated sensitivity to the oral contraceptive which seems to inhibit the pituitary FSH-secreting gonadotrope cells in particular.

Elevated plasma concentrations of beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) are present in vaginally delivered babies in the first 24 h of life. To establish if fetal distress or different types of delivery influence the secretion of these peptides in the neonatal period, we studied 16 vaginally delivered newborns (VD), 11 neonates extracted through elective cesarean section (CS) and 8 babies suffering from acute intralabor fetal distress (FD). In all groups of newborns the plasma levels of beta-LPH and beta-EP were measured in arterial and venous cord blood, at 1 and 24 h from delivery. beta-LPH and beta-EP were determined by specific radioimmunoassays after silicic acid extraction and Sephadex G-75 column chromatography. In cord plasma, there were no differences between arterial and venous concentrations of either beta-LPH or beta-EP in any of the groups. In the 1st h after delivery the plasma levels of VD newborns were similar to umbilical cord values (beta-LPH: 19.9 +/- 5.2; beta-EP: 18.1 +/- 2.4), while those of CS (beta-LPH: 30.6 +/- 4.5; beta-EP: 30.1 +/- 5.8) and FD (beta-LPH: 64.9 +/- 11.8; beta-EP: 65.7 +/- 24.4) showed a significant increase. At the 24th h of life the plasma concentrations of both peptides decreased significantly in the three groups, but CS and FD babies showed significantly higher plasma values than VD newborns (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine infused at a rate of 4 micrograms/kg . min for 120 min induced at the end of the infusion period a clear-cut and similar suppression of circulating PRL levels in normal and puerperal women as well as in patients with hyperprolactinemia either due to a tumor or of unknown etiology. At the discontinuation of the infusion there was a marked PRL rebound above baseline levels in normal subjects and a rapid return to basal levels in subjects with pathological hyperprolactinemia. In contrast, there was no increase in plasma PRL in puerperal women, in whom PRL levels remained suppressed during the whole postinfusion period. The reason(s) for this pattern in puerperal women is presently unknown, although previous estrogen loading of the lactotropes during pregnancy may be involved.

The main aim of this study was to evaluate the effect of dopamine infusion on plasma luteinizing hormone (LH), follicle-stimulating hormone, (FSH) and prolactin (PRL) after acute (1 week postovariectomy) and chronic (postmenopausal women) estrogen withdrawal. We also studied the same group of postmenopausal women after ovariectomy to evaluate the possible influence of other gonadal factors on the endocrine effects of dopamine. In order to have a further indication of neuroendocrine dopamine activity on pituitary secretions, we measured the change in plasma LH, FSH and PRL after the administration of metoclopramide, a dopamine receptor antagonist. Our findings confirm that in fertile women dopamine infusion inhibits plasma LH and FSH levels and show that 1 week after ovariectomy the LH decrease during dopamine administration is still present whereas the FSH decrease is not. In all groups of patients, dopamine significantly inhibited plasma PRL levels. Metoclopramide increased plasma LH levels in reproductive-age women before ovariectomy, but not in postmenopausal women. Plasma FSH levels did not change in any group and PRL levels increased after metoclopramide administration in all subjects. The present findings show that dopamine regulation of LH is impaired in long-term menopause, but not shortly after ovariectomy. These changes in LH control are not followed by similar changes in PRL secretion, which remains under tonic inhibitory regulation by dopamine. The different behavior of LH and FSH after ovariectomy and in postmenopause shows the independence of LH and FSH regulation.

It is note that hyperprolactinemia is frequently associated to chronic renal failure (CRF). The etiopathogenesis of this endocrine disorder is not clearly understood, trying to evaluate the possible hypothalamic-pituitary cause we have evaluated the Prl levels under some pharmacological tests: TRH (200 mcg i.v.),Domperidone (DOM)(10 mg i.v.),Nomifensine (NOM)(200 mg p.o.)and Bromocriptine (BRC)(2.5 mg p.o.) in 3 groups of patients: CRF(8 cases), dysfunctional (8 cases) and tumoral (9 cases) hyperPrl. Prl plasma levels have been evaluated by RIA (kits,Biodata,Roma). In patients affected by CRF either direct (BRC) than indirect (NOM) agonist acting dopaminergic drugs failed to induce a reduction in Prl plasma levels, like to tumoral patients for NOM, and in contrast to the significant decrease after BRC (-70%) in tumoral and (-74%) in dysfunctional and NOM (-50%) observed in dysfunctional patients. CRF and dysfunctional patients showed significant response to TRH and DOM, being prolactinoma bearing patients unresponsive to these tests. These results show an hyporesponsivity of pituitary Prl secreting cells to dopaminergic control suggesting the existence of central etiopathological factor in inducing hyperprolactinemia in CRF patients.

Prolactin (Prl) and growth hormone (GH) responses to different pharmacologic probes acting at the central nervous system (CNS) or the anterior pituitary (AP) level were evaluated in patients with distinct neuroendocrine disorders. Thirteen patients with Prl-secreting tumours (PST), 10 acromegalics (A) and 8 patients with hypothalamic lesions (HL), as assessed on clinical, radiological and surgical grounds, underwent on separate occasions acute testing with the opioid peptide FK 33-824 (0.5 mg iv), the indirect dopamine (DA) agonist nomifensine (NOM, 200 mg po), the DA receptor antagonist domperidone (DOM, 10 mg iv), TRH (200 μg iv) and insulin (ITT, 0.10-0.15 IU/kg iv). All patients were evaluated pre-surgery and 4 of them also post-surgery. Prl and GH were evaluated by RIA at different time intervals following treatments. Peculiar features of Prl and GH response could be evidenced in the patients as follows: Prl: PST patients did not respond either to stimulation by FK 33-824 (12/13) or to inhibition by NOM, (9/10), but 2/8 and 4/12 of them did respond to DOM or TRH stimulation, respectively; 8/10 A and all of the HL patients did not suppress plasma Prl following NOM, but many of them did respond to FK 33-824 (6/10 A, 5/8 HL) and TRH (9/10 A, 6/8 HL); as for GH, PST patients could be divided into FK 33-824 responders (8/12) and non-responders, whereas in only one of the A and in none of the HL patients a consistent response to the peptide was present; a major difference between A and HL patients was the ability of TRH to elicit a GH rise in the former (8/10) but not the latter (0/6). In conclusion, concomitant application of different CNS- or AP-acting stimuli seems to enable better functional connotation of individual disorders, and hence, provide information of value for the underlying pathophysiology.

In 14 patients affected by chronic renal failure (7 males and 7 females) it has been evaluated the secretion of beta LPH, beta EP, ACTH and Cortisol in basal conditions and immediately after a dialytic treatment. For beta LPH and beta EP measurements on each thawed plasma a silic acid extraction and a successive peptides separation by a Sephadex G-75 column chromatography preceeded the two specific RIAs. Basal beta LPH plasma levels resulted significantly higher than in normal controls, while that of beta EP, ACTH and Cortisol were in the normal range. The dialytic treatment was able to increase ACTH and Cortisol plasma levels, without to modified beta LPH and beta EP plasma levels.

In normal subjects, similar degrees of PRL suppression have been reported after L-dopa alone and after a lower dose of L-dopa given in combination with carbidopa (CD), a peripheral inhibitor of L-dopa decarboxylase. In patients bearing PRL-secreting pituitary adenomas, CD-L-dopa induces a minimal suppression of plasma PRL, which is significantly less than after L-dopa alone. Similarly, indirectly acting dopamine (DA) agonists (IADAs), i.e. drugs which release DA and /or block DA reuptake without directly stimulating DA receptors, while capable of suppressing plasma PRL in normal subjects and subjects with puerperal hyperprolactinemia, fail to do so in patients with PRL-secreting adenomas. In the present study, to determine whether in puerperal subjects central nervous system (CNS) dopaminergic function is actually preserved and to elucidate the mechanism (s) underlying the defective CNS dopaminergic function of patients with prolactinomas, we have investigated: 1) whether, like IADA, CDL- dopa suppresses ...

Controversial data have been published in these last years on the dopaminergic tonus of tubero infundibular (TIDA) neurons in hyperprolactinemic subjects. Some authors retain that L-Dopa (LD) stimulation test after pretreatment with Carbidopa (CD), a dopa decarboxylase inhibitor substance, may reveal the presence of a central Dopamine (DA) defect in patient with prolactinoma. To elucidate the reason of so different activity of DA central tonus in subjects with prolactinoma, the effects of Nomifensine (NOM), an indirect DA agonist, DOM, Carbidopa/L-Dopa (CD/LD) and LD, were studied in 26 prolactinoma patients, (basal Prl levels 50 to 280 ng/ml). The patients (24-39 years) were characterized by secondary amenorrhea with sella turcica enlargement at hypocicloidal polytomography. The NOM administration resulted unable to reduce Prl plasma levels in all the patients. On the basis of Prl response to CD/LD administration the patients were subdivided in two groups: group A, which showed a significant decrease of Prl plasma levels and group B, who did not show any significant change. LD test induced a significant Prl decrease in all patients with more evident response in these of group A. DOM administration induced a Prl rise in patients of group A, but failed to change significantly Prl levels in group B subjects. These results confirming the high validity of NOM inhibiting test in the diagnosis of tumoural hyperprolactinemic states, reveal contradictory responses to CD/LD, LD and DOM, with sustain the existence of 2 sub-group of Prolactinomas: with or without a maintained DA central tonus supporting the possibility of different etiopathogenetical factors in inducing a tumoural hyperprolactinemic states.

The effect on plasma prolactin (PRL) of two indirectly acting DA agonists (IADA), i.e., methylphenidate and amineptine was studied in normo- and hyperprolactinemic subjects. PRL responses to methylphenidate and amineptine were compared to those previously obtained with the use of another IADA, namely, nomifensine. In normoprolactinemic women methylphenidate (20 mg, orally) or amineptine (200 mg, orally) induced a significant decrease in baseline PRL (maximal change from baseline 50% at 90 min), a pattern reminiscent of that induced by nomifensine (maximal change from baseline 35% at 120 min). Likewise, in puerperal women (postpartum day 2) methylphenidate and amineptine induced a clear-cut lowering of baseline PRL (40% inhibition at 90 min and 180 min, respectively); nomifensine induced 60% inhibition of resting PRL levels at 150 min. In subjects with pathological hyperprolactinemia (proven or highly probable PRL-secreting tumor or uncertain etiology), previously shown to be unresponsive to the PRL-lowering effect of nomifensine, methylphenidate or amineptine did not significantly lower baseline PRL (maximal change from baseline 8% at 150 min and 3% at 90 min, respectively). In few of these subjects methylphenidate and amineptine failed to lower plasma PRL levels also at doses of 30 and 300 mg, orally, respectively. These data indicate that (1) two other IADA, i.e., methylphenidate and amineptine, are effective PRL-lowering agents in both normoprolactinemic and puerperal subjects, whereas they are unable to lower plasma PRL in patients with proven or probable PRL-secreting tumors; (2) the ability of the different drugs to inhibit plasma PRL in puerperal versus pathological hyperprolactinemia emphasizes the different tuberoinfundibular DA (TIDA) neurotransmission present in the two clinical conditions; (3) in view of the mechanism of action of the IADA, there is a defect in TIDA metabolism or transport in patients harboring a prolactinoma.

Maternal thyroid function in pregnancy is influenced by many factors. This study was undertaken to clarify the mechanism of thyroid regulation in the first trimester of normal pregnancy. We performed the thyrotropin-releasing hormone (TRH) test in eight women in the first trimester (week 6-9) of pregnancy and ten normal women in early follicular phase. Basal plasma levels of free triiodothyronine and free thyroxine were within the normal range in both groups, whereas thyroid-stimulating hormone (TSH) was at the lower limit of the normal range in pregnant women. TRH stimulation evoked a TSH response with a peak of 14.1 +/- 1.2 mIU/ml at 30 min. In control subjects TSH increased in response to TRH with a peak of 7.4 +/- 1.1 mIU/ml at 30 min. Statistical analysis with Student's t test revealed significantly higher TSH levels (p < 0.01) in pregnant women. The most striking finding was the enhanced responsiveness of TSH to TRH stimulation while the thyroid hormones, free triiodothyronine (fT3) and free thyroxine (fT4), remained in the normal range. This response was similar to that observed in central hypothyroidism. These results suggest that the reduction in maternal pituitary TSH levels is due to human chorionic gonadotropin (hCG) inhibition of TRH secretion.

The case of a 37-year-old woman with secondary amenorrhea and clear signs of hyperandrogenism is reported. The patient underwent hormonal evaluation including circadian rhythm of cortisol, gonadotropin-releasing hormone/thyroid-stimulating hormone (GnRH/TRH) test, corticotropic-releasing hormone (CRH) test and dexamethasone suppression test. She also underwent pelvic and adrenal ultrasound examination, adrenal computed axial tomography (CAT) scan and cranial nuclear magnetic resonance (NMR). A mass about 10 cm in size was detected in the left adrenal region. The sella was empty and the pituitary displaced downward. Suspected adrenal adenocarcinoma was confirmed by histological examination after surgical removal of the mass. This case is of interest for physicians because of the mixed androgen and cortisol secretion of the adenocarcinoma in a hyperprolactinemic patient with empty sella. Moreover, it suggests the need to investigate the adrenal gland in patients with hyperprolactinemia and hirsutism.

The Muon detector of the Large Hadron Collider (LHCb) experiment at the Center for Nuclear Research plays a fundamental role in the first trigger level. It is mainly realized by means of a MWPC technology and consists of about 126,000 front-end channels. High efficiency is necessary both at detector and front-end level to satisfy the trigger requirement of five hits per five Muon stations with an overall efficiency of 95%. This corresponds to having a single front-end channel detection efficiency of 99% within a time window of 20 ns and also poses the problem of an accurate time alignment of the whole detector. The problem is addressed by designing two custom integrated circuits, named DIALOG and SYNC, realized in the IBM 0.25 /spl mu/m technology.