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Biomedical subjects

A Tofani

Publications and source records attributed to A Tofani.

54 records · Page 3Linked to original sources

Periovulatory plasma prolactin response to synthetic growth hormone-releasing hormone in normal women.

Following the demonstration of a positive prolactin (PRL) response to growth hormone-releasing hormone (GHRH) in acromegalic and anorexic women, we have injected GHRH (50 micrograms intravenously as a bolus) in normal women during various phases of their menstrual cycle in order to establish whether a positive response was present also in normal subjects. Synthetic GHRH 1-44 elicited a significant increase in circulating PRL levels in eight women studied during the periovulatory phase of the menstrual cycle. In contrast, no significant changes in circulating PRL levels after GHRH administration were found in nine women during the midfollicular phase or in five women during the midluteal phase. A temporal correlation between the midcycle gonadotropin peak and the positive response to GHRH has been observed. Synthetic GHRH elicited the expected increase in GH levels during all phases of the cycle studied. Our data demonstrate that GHRH is capable of stimulating a PRL response in normal subjects and raise the possibility that PRL secretion is regulated by several hormones of hypothalamic origin.

Adult↗

Corticotropin-releasing hormone inhibition of gonadotropin secretion during the menstrual cycle.

To determine whether corticotropin-releasing hormone (CRH) exerts an inhibitory action on gonadotropin secretion in normal fertile women, the effects of CRH on luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cortisol secretion were studied during the menstrual cycle. CRH had no effect on LH release during the midfollicular phase of the cycle. By contrast, IV injection of 100 micrograms CRH elicited significant decreases in LH concentrations during late follicular (-50%) and midluteal (-52%) phases of the cycle. LH concentrations decreased during the four-hours following injection of CRH and returned to those observed during the control period five hours after injection. Similarly, CRH elicited a significant decrease in FSH secretion during the midluteal phase of the cycle. CRH injection induced an increase in cortisol release during all phases of the cycle. These data demonstrate that exogenous CRH administration results in inhibition of gonadotropin secretion in late follicular and midluteal phases of the cycle. These results suggest that elevated endogenous CRH levels resulting in increased cortisol secretion could contribute to decreased gonadotropin secretion and, thus, disruption of reproductive function during stressful conditions in women.

Adult↗

Naloxone inhibition of postprandial growth hormone releasing hormone-induced growth hormone release in obesity.

The effects of opiate receptor antagonist naloxone on growth hormone (GH) release after growth hormone-releasing hormone (GHRH) administration were investigated, before or after feeding, at 13.00 h, in 20 obese women and in 10 normal women. When GHRH was administered to obese women before a meal at lunch time, the mean peak plasma GH levels were very low, while plasma GH responses significantly increased after feeding. Naloxone, infused at a rate of 1.6 mg/h starting 1 h before GHRH administration (50 micrograms i.v. as a bolus), was capable of inhibiting GH release induced by administration of GHRH after feeding. On the contrary, naloxone did not induce significant variations on the fasting GHRH-induced GH release. In normal women, naloxone did not significantly modify the GH response to GHRH, both before and after lunch. The inhibitory effect of naloxone indicates that in obese women there is an increased opioid activity, which could represent an abnormal response of the gastrointestinal tract to food ingestion.

Adult↗

Corticotropin-releasing hormone inhibition of gonadotropin release and the effect of opioid blockade.

We studied the inhibitory effect of exogenous CRH on pulsatile gonadotropin secretion and the role of endogenous opioid peptides in this phenomenon in normal women. To do so, we infused human CRH (100 micrograms/h for 3 h) into 15 normal women during the midluteal phase of their menstrual cycle and studied its effect on both basal (10 women) and GnRH-stimulated (5 women) plasma gonadotropin levels. CRH infusion induced a significant decrease in plasma LH and FSH levels in all women. The decline in plasma LH (62%) was greater than that in FSH (36%). Plasma LH and FSH concentrations returned to basal levels within 30 min after the end of the CRH infusion. CRH infusion did not alter the gonadotropin response to GnRH. We also infused naloxone plus CRH in the 10 women who had received CRH alone during the midluteal phase of a different cycle. Addition of naloxone to CRH (5 women) reversed the LH and FSH inhibition when naloxone was started 1 h after the start of the CRH infusion. When naloxone was started 1 h before CRH infusion (5 women), plasma LH and FSH concentrations did not change. Plasma cortisol increased similarly during both the CRH and CRH plus naloxone infusions; the mean cortisol levels at the end of the CRH and CRH plus naloxone infusions were 497 +/- 40 (+/- SE) and 484 +/- 41 nmol/L, respectively, compared to 240 +/- 14 nmol/L after saline infusion (P less than 0.001). These results demonstrate that in normal women during the midluteal phase of the menstrual cycle, CRH inhibits the secretion of both LH and FSH. The CRH-induced inhibition of gonadotropin secretion is primarily mediated by endogenous opioid peptides, and this effect is not dependent on glucocorticoid levels. We suggest that the disruptive effect of stress on reproductive function in the women could be, at least in part, dependent on decreased gonadotropin secretion induced by elevated endogenous CRH levels.

Adult↗

[Growth hormone-releasing hormone. The physiopathologic aspects and its diagnostic-therapeutic use].

The object of the present study is to review all that in the last years has been discovered about growth hormone-releasing hormone (GHRH), in order to point out both its physiopathological characteristics and its possible diagnostic and therapeutic use. In the first section are summarily reviewed the different studies that culminated in 1982 with the identification of three GRF: GRF(1-37)-OH, GRF(1-40)-OH and GRF(1-44)-NH2, the last of which, by immunohistochemical methods, resulted to be similar to the hypothalamic hGHRH. Then we describe the anatomic distribution of GHRH in man, and its mechanism of action at both receptor and postreceptor levels. On the other hand, the control of the GHRH secretion by peptidergic hypothalamic neurons occurs through four principal monoaminergic systems such as dopaminergic, noradrenergic, adrenergic and serotoninergic ones, and also by cholinergic fibers and by endogenous opiates, all acting to cause the release, into the hypothalamo-hypophyseal portal circulation, of GHRH. In the second section is attracted attention on the GHRH as a diagnostic agent in the two diseases that represent the main alterations of the GH secretion: acromegaly and short stature. According to the different studies considered, it may be concluded that GHRH testing has limited diagnostic usefulness in the clinical evaluation of acromegaly, but allows to discriminate acromegalic patients with ectopic production of GHRH from those with pituitary tumors. For what concerns short stature, the results of observation realized both in adult subjects and in children, all with GH deficiency, by exogenous administration of GHRH, have pointed out that the majority of the GH deficiency patients have hypothalamic disregulation, and not a pure pituitary deficiency as it has been supposed before GHRH discovery. In the third section is attracted attention on the GHRH as a therapeutic agent. Its possible use in the therapy of the children with GH deficiency is of considerable interest, above all in relation to the hypothalamic pathogenesis of their short stature.

Acromegaly↗

Plasma prolactin response to gonadotropin-releasing hormone during benzodiazepine treatment.

Previously we observed that prolactin (PRL) is secreted in response to gonadotropin-releasing hormone (GnRH) in normal women during the periovulatory phase of the menstrual cycle. Because sedative drugs affect the neurotransmitters involved in the regulation of PRL secretion, we investigated PRL responsiveness to GnRH in pre- and postmenopausal female subjects during prolonged treatment with benzodiazepines (six-60 months). In both pre-and postmenopausal patients who were not on benzodiazepine treatment, GnRH infusion (0.2 micrograms/min for 3 hr) was ineffective in eliciting a PRL response. In six premenopausal women treated with benzodiazepines, basal PRL concentrations were not influenced by the drug in four subjects (range 4.0-15.7 ng/ml) and were slightly elevated in two subjects (23 and 30 ng/ml). In six treated postmenopausal women, basal PRL concentrations were in the normal range (7.5-11.0 ng/ml). GnRH infusion induced a progressive increase in PRL concentrations which reached a peak at 120 min in the premenopausal subjects (mean % SEM increase: 64 +/- 30.5%) and at 60-90 min in the postmenopausal subjects (mean % increase: 110.6 +/- 34.7%). A saline infusion, performed on a separate day during benzodiazepine treatment as a control, did not influence PRL.

Adult↗

Differential effects of feeding on the ultradian variation of the growth hormone (GH) response to GH-releasing hormone in normal subjects and patients with obesity and anorexia nervosa.

Nutritional status and metabolic fuels are factors involved in the regulation of GH secretion and GH responses to GHRH. The effects of feeding on GHRH-induced GH release were studied in 13 normal women, 14 obese women, and 9 women with anorexia nervosa. GHRH-(1-44) (50 micrograms, iv) was administered at 0900 h after an overnight fast or at 1300 h after a normal meal at 0800 h, and at the same times 45 min after a 800-Cal meal on different days. The mean peak plasma GH responses to GHRH administered before a meal at 0900 h were 52.8 +/- 5.6 (+/- SE) micrograms/L in normal women, 8.2 +/- 1.3 micrograms/L in obese women, and 53.2 +/- 7.7 micrograms/L in anorexic women. When GHRH was administered before a meal at 1300 h, the mean peak plasma GH levels were lower than those at 0900 h; this reduction was -64.2% in normal women, -64.9% in obese women, and -55.8% in women with anorexia nervosa. After feeding, the plasma GH responses to GHRH were blunted in normal women at 0900 h (-60.9%) and 1300 h (-34.6%) compared with the fasting peak responses. In obese women the plasma GH response to GHRH after feeding was increased compared with that when these women had fasted (+60% at 0900 h and +406.9% at 1300 h). Finally, differential effects of feeding were present in anorexic women; the response was lower at 0900 h (-46.4%) and greater at 1300 h (+50.8%). We conclude that there is an ultradian variation in GHRH-stimulated GH secretion and that the responses differ according to nutritional status and body weight.

Adult↗

Calcium antagonists and hormone release. VI. Effects of a calcium antagonist (verapamil) on the biphasic insulin release in vivo.

The present study was designed to investigate the influence of a calcium antagonist (verapamil) on the two phases of insulin release. The present results confirmed our previous studies and in vitro data, showing that the first phase insulin release is not inhibited by a calcium antagonist and strongly indicated that glucose stimulated insulin secretion has two phases of release: (1) the first phase of release, which is independent from extracellular calcium; (2) the second phase of release, which was inhibited by calcium antagonists, is dependent from calcium uptake from an extracellular source.

Adult↗

Sex-related naloxone influence on growth hormone-releasing hormone-induced growth hormone secretion in normal subjects.

The effect of opiate-receptor antagonist naloxone on growth hormone (GH) release after growth hormone-releasing hormone (GHRH) 1-44 administration was investigated in ten normal men and 18 normal women during different phases of their menstrual cycle. Naloxone was infused at a rate of 1.6 mg/h in women and 1.6- and 3.2 mg/h in men, starting one hour before GHRH administration (50 micrograms iv as a bolus). On different day sessions, naloxone, GHRH, or saline were administered as controls. Naloxone infusion reduced the GHRH-induced GH release in normal women. The mean % inhibition of peak GH response was 83% during follicular phase, 46.5% during periovulatory phase, and 77.6% during luteal phase. On the contrary, in normal men, both doses of naloxone infusion were ineffective in blunting the GH response to GHRH. Our studies indicate that naloxone infusion was capable of inhibiting GH release induced by direct stimulation with GHRH in normal women, suggesting an opiate-antagonist action at the anterior pituitary level. The absence of such an effect in normal men strongly indicates a sex dependence of naloxone effects and suggests a role of the sexual steroid environment in opioid modulation of pituitary hormone secretion.

Adult↗

Clinical relevance of radionuclide angiography and antimyosin immunoscintigraphy for risk assessment in epirubicin cardiotoxicity.

BACKGROUND: Cardiotoxicity is the major limiting factor in anthracycline chemotherapy of advanced neoplastic disease. Epirubicin shows a more favorable therapeutic index than does doxorubicin, but it is still cardiotoxic. Limited data regarding epirubicin cardiotoxicity are available, and suggested guidelines for doxorubicin with left ventricular ejection fraction (LVEF) measurement may not be empirically useful for epirubicin therapy. This study evaluates the diagnostic role of antimyosin immunoscintigraphy for early identification of patients at risk for late pump dysfunction from cardiotoxicity induced by high-dose administration of epirubicin up to high cumulative dosages. METHODS AND RESULTS: Chemotherapy with epirubicin was administered to 36 patients with cancer at a dosing rate of 160 mg/m2 as a bolus injection every 21 days to a cumulative dosage of 960 mg/m2. Radionuclide angiography (LVEF) and antimyosin immunoscintigraphy with heart-lung ratio (HLR) measurements were performed before chemotherapy, at intermediate cumulative epirubicin dosages, at the end of treatment, and during the follow-up. LVEF decreased significantly at the end of the treatment and after therapy discontinuation. HLR values were significantly increased at intermediate epirubicin dosage levels and continued to increase to the end of the treatment but thereafter remained substantially unmodified for 3 to 6 months after therapy discontinuation. A value of HLR >1.85 at intermediate epirubicin dosage level showed a sensitivity of 95% and a specificity of 57% as a predictor of late LVEF impairment. CONCLUSIONS: LVEF appears more useful at high cumulative dosages and during follow-up to monitor late pump dysfunction, whereas HLR may be effective during the early phase of the therapy in determining which patients are at risk for development of late cardiac dysfunction.

Adolescent↗

Fast cancer uptake of 99mTc-labelled bombesin (99mTc BN1).

In human blood, breakdown of gastrin-releasing peptide and other bombesin-related peptides occurs in less than 15 min. This quick enzymatic cleavage might impair the diagnostic use of labelled bombesin (BN). 99mTc-labelled bombesin (99mTc BN1) was injected intravenously and dynamic uptake data were acquired for diagnosing 26 cancers of different origin: 15 breast, 3 prostate, 5 colo-rectal, 1 pancreas, 2 small cell lung cancers and 1 gastrinoma. Background subtracted tumour uptake data were plotted against time and fitted with known mathematical functions. Twenty-three out of 26 cancers showed rapid increase of radioactivity followed by a radioactivity plateau, with some oscillations around the average plateau value. The time to 80% of max activity (T80) was the reference parameter to measure and to compare the uptake speeds. The slowest T80 was 7 min in one T1b breast cancer, gastrinoma reached T80 in 5 min and node-positive prostate cancers in 2 min. N+ breast cancers showed T80 at 3.62 +/- 0.75 min, N- breast cancers at 5.5 +/- 0.88 min (p < 0.02). When all the tumours were considered, N+ tumours showed T80 at 2.68 +/- 1.03 min and N- cancers at 5.5 +/- 0.82 min. In all the cancer types, the uptake of 99mTc BN was faster than 10 min. This result shows the ability of 99mTc BN to image tumours. The faster uptake by N+ versus N- cancers probably depends on the higher blood flow in N+ cancers.

Bombesin↗

[Role of endogenous opioids in the modulation of hypophyseal hormone secretion].

The aim of the present study is to review current knowledge of the endogenous opiates in order to identify both their basic features and their receptors' properties, including the biological effects of their stimulation, and finally their endocrine actions. Since the identification of methionine-enkephalin and leucin-enkephalin, many opioid peptides with higher molecular weight have been characterized, and their origin from specific precursor has been recognized: proopiomelanocortin, preproenkephalin A, preproenkephalin B. In particular we have analyzed the pharmacological properties and the biological effects of beta-endorphin and met -and leu-enkephalins, the most diffuse of opioids. The use of naloxone has permitted the study of endogenous opioid tone and its effects on the release of the pituitary hormones. The present study reports a summary of data in the literature and personal observation indicating that the peripheral sexual steroids are the most important modulators of naloxone effects on endogenous opioid tone. Finally, the paper reports preliminary observations indicating that during naloxone infusion, females with hypothalamic amenorrhoea show a hormonal profile which differs from normal subjects.

Adult↗

[Coexistence of hyperthyroidism and thyroid carcinoma. Description of a clinical case].

The association of hyperthyroidism and thyroid carcinoma, especially multicentric forms, is an unusual event. We present the case of a 49-year-old woman with clinical and radiological findings of hyperfunctioning thyroid nodule that showed, after a subtotal thyroidectomy, histologic evidence of multicentric carcinoma in one lobe and adenoma in the other lobe. The interest of this clinical case is in the coexistence of an independent adenoma with a multicentric carcinoma, revealed by radical surgery that was necessary for the occurrence of a multinodular goiter. The incidence of this situation could be underestimated in consequence of the current surgical approach to the single "hot" nodule and suggests we pay attention to these patients for the possible presence of malignancy in functionally-inhibited thyroid tissue.

Adenocarcinoma↗

Platinum compounds as radiosensitizers in strontium-89 metabolic radiotherapy.

PURPOSE: Strontium-89 is currently used for the treatment of painful bone metastases. This study reports on two preliminary experiences with low-dose platinum compounds, carboplatin and cisplatin, as radiosensitizers in 89Sr therapy. PATIENTS AND METHODS: 30 patients entered the carboplatin study: 15 patients (Group A) were treated with 148 MBq 89Sr followed by carboplatin (100 mg/m2 at 7 and 21 days) and 15 patients (Group B) were treated with 89Sr alone. 12 patients entered the cisplatin study: six patients (Arm 1) received 148 Mq 89Sr plus cisplatin (50 mg/m2) in two administrations (immediately before and 10 days after 89Sr injection) and six patients (Arm 2) received 89Sr plus two placebo administrations. Pain response was assessed 8 weeks after the therapy on the Wisconsin score modifications. RESULTS: No clinically significant adverse effects or myelosuppression by platinum compounds were observed. In carboplatin study a pain response was observed in 20 of 27 (74%) evaluable patients, 13/15 in group A and 7/12 in group B. The pain response in the patients treated with 89Sr and carboplatin was clearly superior to that seen in the patients treated with 89Sr alone (P = 0.025), whereas survival was only marginally better in the combined treatment group (8.1 vs 5.7 months, P = 0.19). In cisplatin study a pain response was observed in 10 of 12 (83%) evaluable patients, 5/6 in Arm 1 and 4/6 in Arm 2. CONCLUSIONS: Low-dose platinum compounds seem to enhance the effects of 89Sr radioisotope therapy on pain from bone metastases without relevant hematological toxicity.

Bone Neoplasms↗