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Biomedical subjects

M Giusti

Publications and source records attributed to M Giusti.

At least 91 records · Page 5Linked to original sources

Sumatriptan does not stimulate PRL and GH secretion in acromegaly.

OBJECTIVE: Serotoninergic receptors are involved in the regulation of PRL and GH secretion. We studied the effects of sumatriptan, a new 5-HT1D receptor agonist, on PRL and GH secretion in active acromegaly. EXPERIMENTAL DESIGN: After their informed consent, all subjects were submitted to sumatriptan or placebo administration in single blind and in a random order. The time interval between the tests was of 7 days. ENVIRONMENT: We examined all patients in the morning, after 12 hours of fasting. All subjects were in recumbent position during the tests. Pulse rate and blood pressure were monitored during the test. SUBJECTS: Eight acromegalics (42-65 years) and 10 age-matched (33-63 years) normal subjects. PROTOCOL: Blood samples were taken after needle insertion kept patent by slow saline solution infusion. PRL and GH secretion were evaluated after sumatriptan (6 mg sc) and placebo. Blood samples were taken before (45, 15 and 0 minutes) and every 15 minutes for 2 hours after sumatriptan or placebo administration. RESULTS: No significant changes in PRL secretion were observed after sumatriptan in both groups of subjects. A significant increase in GH levels after sumatriptan was observed in controls but not in acromegalics. An age-related negative trend in GH response to sumatriptan was observed in controls. CONCLUSIONS: Our study indicated that 5-HT1D receptors are not involved in PRL and GH secretion in middle-aged acromegalics.

Acromegaly↗

[Anorexia nervosa: a follow-up of nutritional, hormonal and psychiatric parameters].

Well known is the need to treat "acute onset" Anorexia Nervosa in care units. Nevertheless even the "successfully treated" patients show a very high percentage of relapse. The aim of our study has been to revalue different clinical, nutritional (hemoglobin, transferrin, IGF1), hormonal (thyroid function, gonadotropins) and psychiatric (EDI: Eating Disorder Inventory Test) parameters in a group of nineteen women aged 20-34 years (median 27 years) admitted to our department 1-11 years (median 6 years) before for anorexia nervosa treatment. On admission their weight loss was -33% +/- 10% according to Ideal Body Weight (IBW); a "low T3 syndrome" was present and all the patients not treated with estro-progestins were amenorrhoic. After a long hospitalization (median 51 days) the patients showed a significant decrease in weight loss (25% +/- 6%; p < 0.01). At follow-up seventeen patients had a weight better than at discharge (13% +/- 12%; p < 0.01) and 9/17 patients non treated with estro-progestins had spontaneous menses. Nutritional (hemoglobin*: 13 +/- 0.2 g%, transferrin*: 313 +/- 57 mg%, IGF-1: 187 +/- 15 ng/ml) and hormonal (LH*: 9.4 +/- 1 mUI/ml, FSH*: 15 +/- 1.3 mUI/ml, T3: 1 +/- 1 ng/ml) parameters were significantly improved (*p < 0.01, p < 0.05) compared to those at admission (hemoglobin: 12 +/- 0.2 g%, transferrin: 218 +/- 58 mg%, IGF-1: 154 +/- 21 ng/ml, LH: 5.6 +/- 0.8 mUI/ml, FSH: 9.5 +/- 1 mUI/ml, T3: 0.8 +/- 1 ng/ml). The EDI test has shown a persistence of anorexic condition ("overt" or latent) in 2/3 of patients. This study confirms the endocrine and nutritional modifications of anorexia nervosa and underlines the persistence of psychiatric ones in a great number of patients including the "clinically cured", justifying long-term follow-up and the high percentage of disease relapse.

Acute Disease↗

Hormones and psychosexual differentiation.

The male phenotype arises from the optimal concordance of chromosomal, gonadal and hormonal sex. Hormonal sex depends directly on the type of gonads that have been formed, and is linked both to the production of hormones and to their optimal effect on target tissues. The present review underlines the fact that psychosexual orientation in the male is also related to factors linked to sex hormones. Many of the experimental and clinical data available militate against the long-held belief that the development of role and gender identity in man is predominantly determined by environmental factors. This study points out the importance of hormonal factors at the CNS level. The most common abnormalities of sexual orientation are homosexuality and transsexualism. Despite their relatively high frequency in the general population, research into possible biological influences in these abnormalities is very scant. The authors of the present paper have reviewed the literature data yielded by biological and hormonal studies on homosexuality and transsexualism. These data seem to support the hypothesis that androgens may be deficient in the CNS of male homosexuals. Morphological or functional (neurotransmitter) anomalies in androgen actions at the CNS level could also favor radical dissociation between psychological sex and gonadal, hormonal and phenotypic sex in transsexualism. In conclusion, the present review seems to indicate that hormonal factors (gonadal and adrenal hormones, hormone receptors, transduction mechanism of the hormonal signal, neurosteroids, neurotransmitters etc.) play a determining role in the formation of gender identity.

Adult↗

Opioid tonus and luteinizing hormone secretion in anorexia nervosa: priming effect with serotonin precursor L-5-hydroxytryptophan during pulsatile gonadotropin-releasing hormone administration.

In anorexia nervosa (AN) luteinizing hormone (LH) release is often impaired during opioid blockade. We investigated whether a restoration of the endogenous sex steroid milieu, together with a rise in central serotonergic tone, could increase LH responsiveness to Naloxone (NAL) in seven young women affected by AN. The spontaneous pulsatility of gonadotropins and their response to gonadotropin-releasing hormone (GnRH) and NAL challenges were tested before and after 13 days of pulsatile GnRH treatment and oral administration of L-5-hydroxytryptophan. Low and unpulsatile gonadotropin levels, responsive to GnRH, but not to NAL, were found before treatment. Pulsatile GnRH brought about a quasi-normal secretory pattern and 17 beta-estradiol increased to preovulatory levels in six of seven patients. On day 13 the lack of response to NAL administration was still present, however. A neuroendocrine disorder seems to be present in AN, which appears more complex than in other forms of hypothalamic amenorrhea.

5-Hydroxytryptophan↗

A cross-over study with the two novel dopaminergic drugs cabergoline and quinagolide in hyperprolactinemic patients.

Cabergoline and quinagolide, two new dopamine agonist drugs with long-lasting activity, are currently under investigation for the treatment of hyperprolactinemia. At present, studies comparing these drugs for tolerability and efficacy in the same patients are lacking. It was our aim to make such a comparison in an open randomized cross-over trial. Cabergoline (0.5 mg twice weekly) and quinagolide (75 micrograms once daily) were given orally. Each drug was administered for 12 weeks. Treatment with the second drug was started after the recurrence of hyperprolactinemia. Twelve women with hyperprolactinemia due to idiopathic disease (n = 6), microprolactinoma (n = 5) or postsurgical empty sella (n = 1) were evaluated. Six women were amenorrheic and 6 were oligomenorrheic. Ten had spontaneous or provoked galactorrhea. Baseline characteristics (age, clinical signs and PRL levels) of patients initially allocated to the two treatment groups were similar. Nine patients completed both treatment cycles and PRL levels were lower under cabergoline (10.7 +/- 3.7 micrograms/L) than under quinagolide (25.0 +/- 7.7 micrograms/L; p < 0.05). One patient discontinued cabergoline because of dryness of the eyes after having completed the quinagolide cycle and 2 patients initially treated with cabergoline discontinued quinagolide because of gastrointestinal symptoms. After completion of the first treatment cycle, the time of recurrence of hyperprolactinemia was significantly longer after cabergoline (14 +/- 7 weeks) than after quinagolide (5 +/- 1 weeks; p < 0.05). At week 12, normal PRL levels (< 20 micrograms/L) were observed in 10 and 6 women during cabergoline and quinagolide, respectively. Only one case was resistant to both drugs. The clinical effects of the two treatments were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Differing responses of cortisol to oCRF during endonasal and oral treatment with DDAVP.

Arginine vasopressin (AVP) exerts a potentiating effect on the responses of cortisol and ACTH to ovine CRF (oCRF). A stimulation test using AVP plus oCRF to assess ACTH reserve has been proposed. In central diabetes insipidus, long-term substitution therapy is commonly undertaken with desmopressin (DDAVP), an analogue of the natural hormone which has a greater antidiuretic action but whose effects on the ACTH-cortisol axis are still controversial. The aim of our study was to evaluate the variations in the responses of ACTH and cortisol to oCRF in various phases of the treatment of central diabetes insipidus: no treatment, endonasal treatment with DDAVP solution and oral treatment with DDAVP in tablet form. Seven patients suffering from central diabetes insipidus underwent testing with oCRF during the various phases of treatment. In the absence of DDAVP treatment, normal responses were registered for cortisol (basal 164.1 +/- 29.4 ng ml-1, peak 396.1 +/- 37.9 ng ml-1; P < 0.05) and ACTH (basal 20.4 +/- 3.9 pg ml-1, peak 86.3 +/- 20.9 pg ml-1; P < 0.05) in all patients. During oral treatment with DDAVP, no variation in cortisol response to oCRF was seen. By contrast, when DDAVP was administered endonasally, a significant reduction in cortisol responsiveness to oCRF (secretory area: 2429 +/- 548 ng ml-1 120 min) was noted in comparison with that found during the other two tests (no treatment: 3070 +/- 704 ng ml-1 120 min; oral DDAVP: 3419 +/- 650 ng ml-1 120 min; P < 0.05) performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

[Behavior of the pituitary-thyroid axis in acromegalic subjects during prolonged intermittent and pulsatile treatment with octreotide].

Octreotide, as well as endogenous somatostatin, inhibits GH and TSH secretion. The drug is employed in the medical therapy of acromegaly. We studied the effects of a long-term (1-120 months; median 12 months) therapy with octreotide (300 micrograms/day) given in 3-times intermittent s.c. administration or in pulsatile s.c. (25 micrograms/120 min) way, upon the pituitary-thyroid axis. Thirteen patients (11 with normal thyroid function, 1 with secondary hypothyroidism, 1 with toxic goiter) with active acromegaly were studied. In the euthyroid patients no significative variations in both TSH levels and thyroid hormones were found during octreotide therapy. In the non-euthyroid patients octreotide did not induce changes in the dosages of drugs acting to thyroid function. The 24-hour IC-TSH levels did not show any variation during octreotide. TSH response to TRH was reduced (P < 0.05) during octreotide therapy. No correlation among TSH, IGF-I and GH levels was observed. Long-term treatment of acromegaly with octreotide reduces TSH response to TRH but do not interfere with both 24-hour IC-TSH levels and thyroid function.

Acromegaly↗

Delta sleep-inducing peptide administration does not influence growth hormone and prolactin secretion in normal women.

The aim of this study was to analyze the effects of delta sleep-inducing peptide (DSIP) on growth hormone (GH) and prolactin (PRL) secretion in eight healthy women with normal cycles (aged 17-36 years). GH and PRL secretion was studied in five women after DSIP (25 micrograms/kg bw IV over 30 min), arginine chlorhydrate (0.5 g/kg bw IV over 30 min) and simultaneous DSIP plus arginine chlorhydrate administration. In three other women the circadian rhythm of GH and PRL was studied during DSIP (25 micrograms/kg bw from 2130h to 2230h) and placebo IV infusion. Serum GH and PRL levels were normal under basal conditions and no effects were noted after the infusion of DSIP. The GH and PRL circadian rhythm was not modified by DSIP administration. DSIP did not influence GH and PRL responsiveness to arginine chlorhydrate. We found that at dosages which are known to modify ECG patterns, DSIP is unable to modify spontaneous or arginine chlorhydrate-induced GH and PRL secretion.

Adolescent↗

The effects of ritanserin on mood and sleep in abstinent alcoholic patients.

A trial was carried out to determine the effect of ritanserin or a placebo on sleep and mood in two groups of abstinent alcoholic patients. Their condition was characterized by both alcohol dependence and dysthymia, associated with a personality disorder. They were included in the study after 30 days of sobriety. Ritanserin was given at a daily dose of 10 mg for 28 days and was preceded (10 days) and followed (2 days) by a placebo. Plasma ritanserin concentration after administration of the 28th dose was higher than after the first dose. Peak levels of ritanserin from the first to the 28th dose increased approximately three-fold. In the ritanserin group there was a reduction of total waking time. Total sleep time increase was associated with significantly larger amounts of nonrapid eye movement sleep. Slow wave sleep and rapid eye movement sleep (in minutes or as a percent of total sleep time) were not significantly modified. Patients on ritanserin achieved a progressive improvement of their dysthymia. As compared to the placebo group, a statistically significant decrease of the Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety was found in the ritanserin group after 1 week of treatment. The absence of an effect in the placebo-treated group suggests that the clinical response and sleep improvement were mainly related to ritanserin administration.

Adult↗

[Diclofenac vs nimesulide in arthrosis. Plasma levels and clinical efficacy].

Diclofenac and nimesulide are non-steroidal antiinflammatory agents advocated for use in painful and inflammatory rheumatic and certain non rheumatic conditions. In Uruguay, these drugs are administered in doses of 100 mg and 200 mg once a day, respectively. Diclofenac is an effective and safe analgesic and antiinflammatory drug. There are scarce data available on the pharmacokinetic profile of nimesulide. These facts encouraged us to undertake the present study on clinical efficacy, tolerance and pharmacokinetics of nimesulide, controlled with sustained release diclofenac. Twenty patients with osteoarthritis, stage II-III, according to a clinical-radiological evaluation, were selected for the study. Patients were assigned at random to treatment A (Voltaren sustained release, 100 mg) or B (Nodo regular formulation, 200 mg) once a day. A double blind study with active drug and controlled parallel groups was designed. After a washout period of one week patients were treated with active medication during 84 days, and clinical controls every 14 days ensued. Experienced rheumatologists assessed pain and other clinical symptoms. Blood samples were drawn on days 7, 49 and 91 of the study, ten hours after the morning dose, and plasma diclofenac and nimesulide concentrations were measured. On day 7 and 91, blood counts and biochemical laboratory studies were performed (namely, hemoglobin, RBC, WBC, leucocyte differential count, platelet count, alkaline phosphatase, ASAT, ALAT, creatinine, etc.) Already two weeks after the study had begun, significant improvements in clinical parameters assessed were seen for both treatments. A trend to accumulation of diclofenac and nimesulide along the three months of treatment was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of cholinergic tone on growth hormone-releasing hormone-induced secretion of growth hormone in normal aging.

Aging is associated with an impairment in the GH response to GHRH and to several other stimuli of GH secretion. We evaluated the effect of pyridostigmine (PD) or placebo pretreatment (Protocol A: placebo or 120 mg PD orally at 8 a.m.; Protocol B: placebo or 60 mg PD twice orally at 9 p.m. and 7 a.m.) on GH responsiveness to GHRH (1 micrograms/kg BW bolus i.v. at 9 a.m.) in 15 normal elderly males (65-92 years) and in 14 normal young adults (20-37 years). GH response to GHRH was significantly reduced in elderly subjects compared to young adults (p < 0.05). PD (Protocol A) increased GH release in both elderly and young subjects. In elderly men, PD enhanced GH response to GHRH. The phenomenon was more evident when PD was administered according to Protocol B (p < 0.01). The area under the curve of GH was significantly greater after PD plus GHRH than it was after placebo plus GHRH (p < 0.01). In young adults, PD induced an increase in GH responsiveness to GHRH when administered according to Protocol A (p < 0.05) but not Protocol B. Both GH peak and AUC of GH after PD plus GHRH (Protocols A and B) in elderly subjects were not significantly different from the same parameters found in young subjects after placebo plus GHRH. Our data confirm that pituitary somatotrophin responsiveness to GHRH in man changes with aging. PD restores GH responsiveness to GHRH in elderly subjects. The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Delayed puberty in uremia: pituitary-gonadal function during short-term pulsatile luteinizing hormone-releasing hormone administration.

Pubertal development is frequently delayed or disordered in children with chronic renal failure. Both neuroendocrine and peripheral alterations due to uremia have been hypothesized to explain the impairment in the pituitary gonadal axis. The aim of the present study was to evaluate quantitative (immunological) and qualitative (biological) LH secretion, as well as FSH and sex steroids, before and during 7 days of sc LHRH administration (136-150 ng/kg bw every 120 min) in 5 uremic children (13.1-14.8 yr) with delayed puberty. Six nonuremic children (13.2-17.8 yr) with delayed puberty underwent the same schedule and served as control group. On day 0 mean immunoreactive LH (I-LH) levels were higher in uremic (4.5 +/- 0.9 mIU/ml) than in nonuremic (1.9 +/- 03 mIU/ml; p < 0.05) subjects while no differences were observed in bioactive LH (B-LH) levels (2.9 +/- 0.7 mIU/ml vs 2.4 +/- 0.3 mIU/ml). In both groups of subjects testosterone was at prepubertal levels. Spontaneous I-LH and B-LH pulses were observed sporadically in both uremic and nonuremic subjects. Short-term pulsatile LHRH administration induced significant increases in B-LH, I-LH, FSH and testosterone. The B/I LH ratio increased from day 0 (0.7 +/- 0.2) to day 7 (1.3 +/- 0.4; p < 0.05) in uremics while it showed wide fluctuations in nonuremic subjects. On day 7, 4 uremic and 5 nonuremic subjects showed a pulsatile release of B-LH after exogenous LHRH pulses. Our data document that in uremia there are qualitative as well as quantitative abnormalities in pituitary gonadal secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The effect of a met-enkephalin analogue on growth hormone, prolactin, gonadotropins, cortisol and thyroid stimulating hormone in healthy elderly men.

The aim of the study was to evaluate the effect of the guanyl derivative of the opioid analogue D-ala2,MePhe4-Met-enkephalin-(o)-ol (G-DAMME) on pituitary secretion in healthy elderly men. Nine healthy elderly men (65-88 years) and 10 young adults (20-30 years) were studied. GH, PRL, gonadotropins, cortisol (to evaluate the effect on ACTH) and TSH were measured after G-DAMME (0.25 mg iv) or placebo administration. In elderly men, the GH response to G-DAMME was reduced or absent, while prompt GH release was found in all young men. G-DAMME lowered LH levels in young men but not in elderly men. No significant variations in FSH levels after G-DAMME and placebo were noted in either group of subjects. A similar and significant rise in PRL and TSH, and a fall in cortisol, after G-DAMME was observed in both elderly and young adults. We have demonstrated that the sensitivity to opioid modulation by G-DAMME on PRL, TSH and cortisol secretion is unchanged with aging. On the other hand, the data indicate that LH and GH responsiveness to G-DAMME change with age.

Adult↗

Therapeutic strategies in a male with delayed puberty.

Therapeutical strategies in male with delayed puberty. Delayed puberty (absence of pubertal modifications after 14-15 years of age) due to transitory deficit of LHRH secretion often constitutes a difficult differential diagnostic problem for conditions of permanent LHRH deficit which can be identified only after 18 years of age in the idiopathic hypogonadotropic hypogonadism. After a period of clinical observation short-term therapy with pulsatile LHRH administration may take place. Therapy can be necessary: to document the functional integrity of the pituitary-gonadal axis; to promote pubertal modification such as to improve and physiologically sustain the patient; to tray a neuroendocrine activation of endogenous LHRH-LH secretion. Also delayed puberty linked to uremia seems to respond to short-term pulsatile LHRH administration. Pulsatile LHRH administration is the most physiological therapeutical approach to subject with delayed puberty. It seems to constitute a valid alternative to the therapy with testosterone or gonadotropins.

Adolescent↗

Androgen replacement therapy in male patients with rheumatoid arthritis.

A hypogonadic condition characterized by low serum testosterone levels has been identified in male patients with rheumatoid arthritis (RA). Seven men with active RA were treated daily for 6 months with oral testosterone undecanoate plus a nonsteroidal antiinflammatory drug in an attempt to evaluate the immunologic response, the overall clinical response, and the sex hormone response to such replacement therapy. At the end of the 6 months, there was a significant increase in serum testosterone levels (P less than 0.05), an increase in the number of CD8+ T cells, and a decrease in the CD4+:CD8+ T cell ratio. The IgM rheumatoid factor concentration decreased significantly (P less than 0.05). There was a concurrent significant reduction in the number of affected joints (P less than 0.05) and in the daily intake of nonsteroidal antiinflammatory drugs (P less than 0.01). The well-known immunosuppressive action of androgens probably contributed to our findings in these RA patients.

Administration, Oral↗

Biological activity of luteinizing hormone in uraemic children: spontaneous nocturnal secretion and changes after administration of exogenous pulsatile luteinizing hormone-releasing hormone--preliminary observations.

Normal pubertal progression is associated with quantitative and qualitative changes in gonadotrophin release. Uraemic children show a delayed or disturbed puberty. We have therefore examined nocturnal gonadotrophin and sex steroid secretion in seven males and three females [age 11-15 years, pubertal stage (PS) 1-3] with chronic renal failure on conservative treatment. In addition to immunoreactive luteinizing hormone (i-LH) we have measured the biological activity of LH (b-LH). Nine children aged 12-17 years with PS 1-3 and normal renal function served as a control group. In two uraemic children, i-LH, b-LH, follicle stimulating hormone and sex steroids were evaluated before and 7 days after pulsatile LH-releasing hormone (LHRH) administration (150 ng/kg body weight subcutaneously every 120 min). Mean i-LH levels were higher in uraemic children than in controls. An increase in i-LH during sleep was found in all controls and in eight of ten uraemic subjects. Mean b-LH levels were lower during sleep and the b/i LH ratio was reduced in uraemic children with PS 2-3 whether asleep or awake compared with controls. Pulsatile administration of LHRH provoked a rise of i-LH and b-LH levels with an increased b/i LH ratio, suggesting an intact pituitary responsiveness. These preliminary data indicate that the gonadotrophin control of LH is abnormal in uraemic children, and that biopotency of LH secretion might be improved after short-term pulsatile LHRH administration.

Adolescent↗