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Biomedical subjects

S Fusi

Publications and source records attributed to S Fusi.

32 records · Page 2Linked to original sources

Effects of pharmacological doses of testosterone and dihydrotestosterone on the hypothalamic-pituitary axis function of Klinefelter patients.

Six patients affected by Klinefelter's syndrome (KS) were treated with testosterone propionate (TP) 100 mg im daily for 4 days and one month later the same patients received dihydrotestosterone propionate (DHTP) 100 mg im daily for 4 days. Plasma levels of LH, FSH, PRL, testosterone (T) and dihydrotestosterone (DHT) have been measured in these patients for 8 days during and after TP and DHTP treatment. TP administration reduced LH levels only transiently, while a more prolonged reduction was observed for FSH. DHTP administration produced a late and transient reduction of LH and a very late reduction of FSH. PRL levels increased significantly during and after TP administration. Our data suggest that in Klinefelter patients: i) DHT is less effective than T in suppressing gonadotropin concentrations, ii) the increased PRL levels observed during and after TP administration are not due to a pure androgenic effect, but are probably related to an increased conversion rate of T to estradiol.

Adolescent↗

Parameters of interferon action: I. Immunological effects of whole cell leukocyte interferon (IFN-alpha) in phase I-II trials.

The antitumor mechanisms of the interferons (IFN) have yet to be fully elucidated. Augmentation of natural killer (NK) cell activity in vitro and in vivo by IFN has regularly been assessed in clinical trials. We have measured NK activity against K562 target cells at various effector-to-target ratios, in patients receiving leukocyte IFN-alpha (HuLeIFN) in various schedules, as well as T-cell subsets determined by indirect immunofluorescence using Leu series monoclonal antibodies (Becton-Dickinson). The effect of HuLeIFN on the endocrine system has also been examined in selected trials. The preliminary results of these studies reveal that NK activity rose during the first 8 days of HuLeIFN therapy in patients with initially low levels of target cell lysis (less than 50% NK activity at either 50:1 or 25:1 ratios). Tachyphylaxis, with a decremental effect of HuLeIFN on NK activity, ensued during treatment, whether at the same or escalated doses. NK activity rose repeatedly during intermittent schedules of i.m. HuLeIFN given daily x 5 every 21 days with escalation cycles. A decreasing trend in the ratio of Leu 3a to Leu 2a (helper phenotype/suppressor phenotype) was also seen overall. Of the endocrine parameters evaluated, the only remarkable finding was an increase in serum cortisol level following ACTH stimulation following HuLeIFN. Intramuscular HuLeIFN has been shown to augment NK activity, to perturb the T-cell-lymphocyte balance, and to affect the pituitary-adrenal axis in vivo.

Adenocarcinoma↗

Parameters of interferon action: II. Immunological effects of recombinant leukocyte interferon (IFN-alpha 2) in phase I-II trials.

Twenty-nine patients receiving recombinant interferon (IFN-alpha 2; Schering Plough Corp., Bloomfield, NJ) were studied for changes in natural killer (NK) activity measured by a 4-h 51Cr release assay against K562 cells, and T-cell subsets were determined by indirect immunofluorescence of Leu series monoclonal antibodies (Becton-Dickinson, Mountain View, CA). Seventeen cancer patients received daily i.m. injections of IFN-alpha 2 from 3 to 100 x 10(6) U/day for 28 consecutive days or to tolerance. Twelve of an anticipated 16 melanoma patients have been studied during a phase I trial using the i.v. route with the same recombinant IFN-alpha 2. NK activity rose during the first week of i.m. therapy from 49 +/- 6.5 to 67 +/- 6.2 (mean +/- SE, day 8) at both high (greater than or equal to 30 x 10(6) U/day) and low (less than or equal to 10 x 10(6) U/day) doses. This trend was not observed during therapy by the i.v. route at similar doses, in which NK activity tended to decrease in patients receiving 30 x 10(6) U/day or more. Changes in T-cell subsets were observed in both trials; Leu 3a/2a (helper phenotype/suppressor phenotype) ratio rose twofold in patients receiving i.m. IFN-alpha 2 at higher doses. A rise in Leu-3a+ and a fall in Leu 2a+ T cells account for the change. No change in T-cell subsets was seen in patients treated at low doses (less than or equal to 10(7) U/day) by the i.m. route. By contrast, the Leu 3a/2a ratio fell by 50% in patients who received 30 x 10(6) U/day or more of IFN-alpha 2 by the i.v. route, reflecting a fall in Leu 3a+ cells and a rise in Leu 2a+ cells. Thus, opposite changes in several parameters of immune competence occurred during treatment of patients with melanoma and other cancers, with a single recombinant IFN subspecies given by two different routes.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Evaluation↗

Klinefelter's syndrome: a study of its hormonal plasma pattern.

Plasma testosterone (T), dihydrotestosterone (DHT), 17 beta-estradiol (E2), 17-hydroxyprogesterone (17-OHP), androstenedione (delta), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 5-androstene-3 beta-17 beta-diol (A-diol) and cortisol (F) have been measured in a group of normal males and in a group of patients with Klinefelter's syndrome (KS) before and after hCG stimulation. Significantly lower baseline levels of T and DHT and significantly higher baseline levels of E2 were found in patients with KS. No significant differences were found between baseline levels of 17-OHP, delta, DHEA, DHEAS, A-diol, and F. After hCG stimulation between T, DHT, E2 and 17-OHP levels showed a significant increase in the two groups of subjects. The percentage variation of T and DHT, however, was much less important in Klinefeiter patients, while E2 and 17-OHP did not show a significantly different pattern from that of normal controls, hCG administration did not produce any significant variation of delta, DHEA, DHEAS, and F in the two groups of subjects, while A-diol levels increased significantly in normal subjects, but not in Klinefelter patients. Our data may be consistent with the hypothesis that testicular steroidogenesis in Klinefelter patients is impaired below the 21-C-steriod level not only at delta 4 but also at the delta 5 pathway.

Adolescent↗

Hormonal studies in a male with a 47,XXX chromosome constitution: comparison with the hormonal pattern of a 46,XX male and patients with Klinefelter's syndrome.

Chromosome analysis in peripheral blood lymphocytes and skin fibroblasts of a 18 year old chromatin-positive man showed a 47,XXX karyotype. The following hormonal studies were performed: 1) FSH and LH response to GnRH; 2) hypothalamic-pituitary responsiveness to short-term testosterone administration; 3) plasma levels of testosterone, dihydrotestosterone, 17-hydroxyprogesterone, estradiol before and after hCG stimulation. Results were compared with similar studies performed in a 46,XX male and in a group of patients with Klinefelter's syndrome. Our data support the hypothesis that this rare cytogenetical disorder can be considered, from the endocrine point of view, as a variant of the Klinefelter's syndrome.

Adolescent↗