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Biomedical subjects

S Fusi

Publications and source records attributed to S Fusi.

35 records · Page 2Linked to original sources

Study of endocrine function in myotonic dystrophy.

Endocrine function was studied in 12 patients, 7 men and 5 women, with myotonic dystrophy (MD). Growth hormone (GH) was within normal limits in all the patients and there was no response to arginine stimulation. Prolactin (PRL) was above normal in only 2 cases (one man and one woman) and the response to TRH was below normal in 2 patients and slightly above in one. The GnRH test yielded a reduced LH response in 4 of the 7 men and none at all in the 4 women in whom it was done. The FSH response was below normal in only one of the 7 men and in 3 out of 4 women. The testosterone assay after HCG stimulation was borderline high in 2 out of 6 men and below normal in one. The level of thyroid hormones (T3, T4, FTI, TSH) was normal in all patients except one, whose FTI and T4 level were below normal. In the TRH test TSH was raised in only one of the 6 patients tested. The circadian rhythm of cortisol was absent in 3 out of 10 patients and 3 out of 8 patients showed no response to ACTH stimulation. The results of the study suggest that endocrine alterations are fairly frequent in MD but that they are neither specific nor correlated with disease severity or duration.

Adrenal Cortex↗

Reversal of postburn immunosuppression by the administration of vitamin A.

The effect of high doses of vitamin A was evaluated on the suppression of cellular immunity after a 30% body surface area experimental scald burn in a mouse model. Male CBA/J mice were treated postburn with daily intraperitoneal injections of either 3000 IU of vitamin A or an equal volume of 0.9N saline. Similar groups of unburned mice were also studied as controls. At the seventh postburn day, one-way mixed lymphocyte reactions were tested for each group with whole spleen cells of CBA/J mice used as responders and mitomycin C-treated whole spleen cells of C57 BL/6 mice used as stimulators. When results were expressed as mean percentage of the values of control animals, no significant difference was observed between the saline-injected unburned control group (taken as 100%) and the vitamin A-treated unburned control groups (89%). The burned animals treated with saline showed suppression to 21% of the control values. However, the burned animals treated postburn with vitamin A improved the response rate dramatically to 52% of control values. This improvement over the untreated burned animals was significant in all experiments performed (p less than 0.02). This study suggests that vitamin A may be an effective agent in the reversal of cellular immunosuppression after burns.

Animals↗

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↗

Multiple views of the response of an ensemble of spectro-temporal features support concurrent classification of utterance, prosody, sex and speaker identity.

Models of auditory processing, particularly of speech, face many difficulties. These difficulties include variability among speakers, variability in speech rate and robustness to moderate distortions such as time compression. In contrast to the 'invariance of percept' (across different speakers, of different sexes, using different intonation, and so on) is the observation that we are sensitive to the identity, sex and intonation of the speaker. In previous work we have reported that a model based on ensembles of spectro-temporal feature detectors, derived from onset sensitive pre-processing of a limited class of stimuli, preserves significant information about the stimulus class. We have also shown that this is robust with respect to the exact choice of feature set, moderate time compression in the stimulus and speaker variation. Here we extend these results to show a) that by using a classifier based on a network of spiking neurons with spike-driven plasticity, the output of the ensemble constitutes an effective rate coding representation of complex sounds; and b) that the same set of spectro-temporal features concurrently preserve information about a range of qualitatively different classes into which the stimulus might fall. We show that it is possible for multiple views of the same pattern of responses to generate different percepts. This is consistent with suggestions that multiple parallel processes exist within the auditory 'what' pathway with attentional modulation enhancing the task-relevant classification type. We also show that the responses of the ensemble are sparse in the sense that a small number of features respond for each stimulus type. This has implications for the ensembles' ability to generalise, and to respond differentially to a wide variety of stimulus classes.

Acoustic Stimulation↗