In this study we evaluated the effects of placebo or acute bromocriptine (BC) administration (2.5 mg orally) on plasma catecholamines, systolic and diastolic blood pressure (BP), heart rate, and plasma PRL in six normal subjects [group I, mean age 33.2 +/- 5.4 (SD) yr] in the supine as well as upright position. BC induced a significant decrease in plasma norepinephrine in the supine [167.7 +/- 16.8 (SEM) vs. 101.9 +/- 33.7 pg/ml, P less than 0.005] and upright positions [397.3 +/- 27.7 vs. 211.3 +/- 26.7 pg/ml, P less than 0.005], a decrease in systolic and diastolic BP and a decrease in plasma PRL (P less than 0.01). After standing, epinephrine levels increased significantly (53.6 +/- 11.8 vs. 226.4 +/- 71.0 pg/ml, P less than 0.05). The study was repeated in a second group of seven normal subjects (mean age, 32.3 +/- 12.9 yr) after placebo or metoclopramide (20 mg orally) plus BC. In this group metoclopramide, a central and peripheral antidopaminergic agent, counteracted the BC-induced effects found in group I, both in the basal and stimulated conditions. Plasma PRL increased significantly (P less than 0.025). Finally, to assess the effect of peripheral dopaminergic blockade on BC-induced changes in sympathetic outflow, we repeated the study in seven normal subjects (group III, mean age, 30.1 +/- 5.0 yr) after placebo or domperidone (20 mg orally) plus BC. Domperidone blocked the effects of BC on norepinephrine and BP in the supine position. On standing there was a significant decrease in systolic (P less than 0.05) and diastolic (P less than 0.05) BP and an increase in epinephrine levels (58.9 +/- 12.2 vs. 109.8 +/- 24.6 pg/ml, P less than 0.05) was still observed. Plasma PRL increased significantly (P less than 0.025). The results of this study suggest that the inhibition of sympathetic outflow induced by BC is peripherally mediated. As peripheral dopamine receptor blockade did not counteract all the effects after BC during standing, dopaminergic modulation of central reflex sympathetic activation is suggested.

Multiplex microsatellite analysis is a noninvasive, rapid, inexpensive and reproducible method for screening for and monitoring superficial transitional cell carcinoma. It should be considered an alternative method to urinary cytology and it should also be considered in the presence of urine sediment inflammatory cells.

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We have investigated the frequency and spectrum of CDKN2A/CDK4 mutations in 23 cutaneous melanoma families from Central Italy (Tuscany). Three distinct mutations were identified in five families. One mutation, p.G23S, was present in three families. Several lines of evidence indicate that p.G23S is a pathogenic mutation: it is located in the functionally important first ankyrinic domain of p16, it was not detected in a sample of 100 control individuals, and it was present in all tested affected individuals from the three families. Haplotype analysis showed a common ancestral origin of the p.G23S mutation. Our data show that the p.G23S mutation is an important cause of hereditary melanoma in Tuscany.

This study highlights the predictive value of loss of heterozygosity analysis on interferon-alpha in patients with nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin.