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The mechanism of prolactin (PRL) unresponsiveness to repeated sulpiride (SUL) administration was investigated by means of two experimental protocols. The first one was carried on in seven male volunteers (age 24 to 34 yr) and consisted of two phases separated by a 5-day interval. In both phases 1 mg/kg of SUL was given im and repeated, 24 h later, together with either placebo (PL, 2 ml saline iv) or TRH (200 µg iv). 7–10 days later a standard TRH test (200 µg iv) was performed. In the second protocol the usual dose (1 mg/Kg im) of SUL was administered alone and, 24 h later, together with 0.1 U/Kg iv of insulin (insulin tolerance test: ITT) to six male volunteers (age 20 to 32 yr). A control standard ITT (0.1 U/Kg iv) was also performed 7–10 days later. Plasma samples for the evaluation of PRL were taken in basal conditions and at regular intervals after each drug administration. In the first protocol, PRL shQwed a significant increase (peak values at 30 min) after SUL administration in both phases (phase A: 54.8 ± 5.6 ng/ml, mean ± SE vs 6.4 ± 0.3, p< 0.001. Phase B: 77.5 ± 3.9 vs 7.0 ± 0.6, p< 0.001). Twenty-four h later, PRL levels were still higher than basal and were not affected by the administration of SUL + PL or SUL + TRH. Also in the second protocol, SUL alone induced a significant PRL increase (peak values at 30 min: 47.1 ± 7.2 vs 4.2 ± 0.5, p< 0.005). Twenty-four h later PRL levels were still higher than in basal conditions (12.4 ± 1.5, p< 0.01 vs day one) and were modified by SUL + ITT administration only mildly (at 60 min: 17.0 ± 2.8, p< 0.05 vs basal) and significantly less than what observed after SUL and insulin alone (p< 0.005, p< 0.05, respectively). SUL then seems to induce a prolonged unresponsiveness of pituitary PRL secreting cells to multiple administration apparently not overcome by different stimuli (TRH, ITT), probably due to an alteration distal to the dopamine receptor.

Summary: In order to demonstrate the suggested failure of the serotoninergic system in human obesity and to evaluate the role of central serotoninergic activity in prolactin (PRL) and thyroid stimulating hormone (TSH) release in this condition, 13 euthyroid obese and 9 healthy women of normal weight were studied. A TRH test (200 �g i. v.) was performed before and after administration of fenfluramine (FF) 60 mg b. d. for 14 days. In the controls, FF did not modify the expected significant increase in PRL induced by TRH. In obese patients, however, the PRL levels was significantly increased after TRH, but the increase was less than in the controls. After FK the PRL response to TRH was larger than in the pretreatment phase, with values similar to those observed in normal subjects. In neither group FF did change the TSH-stimulating effect of TRH, but the hormonal response in obese patients was greater than in the controls. The restoration of the responsiveness of PRL to TRH after central serotoninergic stimulation confirms the hypothesis that a failure of the serotoninergic system may occur in human obesity. Since FF does not interfere with the secretory pattern of basal and stimulated TSH in normal or obese subjects, the serotoninergic system does not seem to play a major role in the control of TSH secretion.

T1and T2relaxation times were calculated, before radiation therapy, in 30 patients with cervical carcinoma. Eight healthy young women were submitted to magnetic resonance imaging (MRI) to determine T1and T2times of the normal cervix. Magnetic resonance imaging was repeated, in 22 patients, during radiation therapy and at follow-up. During treatment and follow-up, patients with complete tumour response showed a significant T1reduction compared with the pre-treatment values. With persistence of palpable or visible tumour, T1times showed a small decrease during therapy, and a marked increase at subsequent examinations. The results suggest that the modifications of T1relaxation times, during radiation therapy and follow-up, could be considered as a useful discriminant between patients with differing tumour response.

A system based on Macintosh™, Hypercard™ and a local network was developed at the University and Hospital Department of Radiation Therapy, Florence, Italy, to manage the clinical records as a complex data structure (data, texts, drawings and image storage and retrieval). After 4 years, the system produces over 2000 new charts a year and manages more than 15000 clinical records. Electronic records are produced, printed and updated in their traditional form to be put on file in our archive. On-line consultation of the clinical records is possible from every workstation of the structure even as it is producing, updating, or printing a chart. Physicians and clinical clerks, with different access privileges, currently use the system for all these purposes. The clinical records are typed by secretaries who receive dictation on microcassettes. No extra staff were necessary to set up and manage the system and training was simple. The new system changed neither the organization and structure of the traditional records, nor the flux of information; new tools (computers, printers and a network) were introduced to manage the information and the charts. The author describes the aims of the original project and the result.

In 1960-1985, 35 patients with ovarian dysgerminoma were referred after surgery to the Radiation Therapy Unit of the University of Florence. Twenty-seven of these cases were analysed with regard to lymphangiography findings before radiation therapy. Nodes were judged as positive in 18 of the 27 cases (44%) and in all the positive cases the paraaortic nodes were involved. The relevance of lymphography in the staging and follow-up of patients with ovarian dysgerminoma is discussed.

Prostate Specific Antigen (PSA), PSA density, PSA excess, and PSA age-specific range have been compared in 331 subjects (35 cancers, 296 benign) with equivocal findings at screening by PSA or palpation + transrectal ultrasonography. The specificity of PSA using a cut-off of 4 ng/ml was only 0.49. A cutoff of 10 ng/ml improved the specificity to 0.88 but the sensitivity decreased from 0.97 to 0.63. The sensitivity and specificity for PSA density (cutoff 0.15), PSA excess (cutoff -5), and age-specific range were 0.86 and 0.80, 0.80 and 0.82, and 0.91 and 0.67, respectively. Avoided benign biopsies vs missed cancers on the basis of PSA density, PSA excess and PSA age-specific range would have been 19 and 5, 26 and 7, and 16 and 3, respectively. Methods adjusting for prostate volume allow a better interpretation of PSA values and may reduce the benign biopsy rate, but the consequent cost of delayed cancer diagnoses when the choice of biopsy is based only on these methods seems unacceptable.

The mechanisms of prolactin (PRL) unresponsiveness to repeated sulpiride (SUL) injections were investigated in 7 normal males. The experimental protocol consisted of two phases, separated by a 5 day interval. In both phases the administration of 1 mg/kg i. m. of SUL was followed 24 hours later, by the administration of the same dose of SUL together with either placebo (PL, 2 ml saline i. v.) or TRH (200 mcg i. v.). A control TRH test (200 mcg i. v.) was also performed. PRL showed a significant increase after the administration of SUL alone in both phases. Twenty-four hours later plasma PRL was still higher than the basal level and it was not significantly modified by administration of SUL+PL, or by SUL+TRH. The data seem to show that the lack of responsiveness of PRL to repeated administration of SUL is not due to refractoriness of dopaminergic receptors but probably to exhaustion of the hypophyseal PRL pool.

Many patients (pts) treated for MD, ELC, BC and CC are cured of their diseases. They are therefore exposed to the risk of developing a SMT. These four groups of pts, however, are quite different as far as their features are concerned. We considered of interest to compare the incidence of SMT in the different clinico-pathological and therapeutic subsets of the four series, along with the effects of SMT on survival.We studied 1121 HD ptsconsecutively treated 1960 through 1988 at the Florence Radiotherapy Department (743 Clinical Stage I–II, 378 with CS III and IV; 745 treated with radiotherapy -RT- alone, 104 with chemotherapy alone -CT- and 272 with RT+CT). Cause specific survival at 20 years is 63%. Among these pts 74 SMT have been observed, for a cumulative incidence at 20 years of 18%. Cumulative survival after the diagnosis of SMT was 26% at 7 years, for the solid tumors, 9% at 3 years, for the leukemias. The second group consists of 424 ELC ptsconsecutively treated 1970 through 1992 in Florence (308 glottic; 111 supraglottic; 5 subglottic; all treated with radiotherapy). Cause specific survival at 10 years is 82%. Among these pts, 36 SMT have been observed, for a cumulative incidence at 10 years of 17%. Cumulative survival after the diagnosis of a SMT was 23% at 5 years. We studied also survival data and incidence of SMT in pts treated at our institution for BCand CC, whose clinical and therapeutic features are largely different from those of the two groups already described. Some general statements will be drawn.