The role of thymidylate synthase levels in the prognosis and the treatment of patients with colorectal cancer.

Inhibition of Thymidylate Synthase (TS) by the 5-Fluorouracil (5Fu) active metabolite Fluoro-deoxy-uridine-monophosphate (FdUMP) is considered to be the main mechanism of action of 5Fu. TS level from tumors and normal mucosa of 62 untreated patients who underwent surgery for primary colorectal adenocarcinoma was performed. The aim of this study was to evaluate the possibility of considering the TS level as a prognostic factor of the disease. A large variation in the level of the enzyme was found among tumors. Our data demonstrate that there is no association with age, sex, and tumor size; however there are significant relationships between TS levels and staging and histological grading. In fact the TS values are higher in Dukes' A and in G1 than in Dukes' D and G3 tumors (p < 0.05). Another significant association has been found between the TS level and tumor site: pts with right colon neoplasias had higher TS levels than pts with left and rectum ones. An interesting trend was found between the TS levels and survival parameters. Pts who had lower TS levels had a significantly increased risk of death (p < 0.05) over pts with a higher outcome. Our data support the hypothesis that a high TS level is a favourable prognostic factor in human untreated colorectal carcinomas according to our previous preliminary data (1).

A new method to measure cardiac inositol levels in intact animals.

Inositol levels have been studied in cellular cultures and recently by perfusion of isolated hearts. The study was aimed to assess inositol turnover in rabbit hearts from intact animals. Thirty rabbits were injected i.v. three times (every 12 hr) with 25 microCi/kg of myo-3H-inositol. The rabbits 12 hr after the last injection were killed and the hearts perfused according to Langerdorff technique. Systolic and diastolic ventricular pressures (SVP, DVP), dp/dt, and coronary flow (CFl) were measured. The hearts (n = 14) were perfused under aerobic conditions and 16 hearts under ischemic conditions for 30 min. In addition, 5 hearts were perfused under aerobic conditions for 10 min, and 6 hearts were perfused under ischemic conditions for 10 min. Samples of myocardial tissue were taken from both groups at the end of 10-min and 30-min period of perfusion, and cAMP and inositol phosphates were assayed. The hearts subjected to ischaemia showed changes of cAMP and 3H-inositol. The cAMP was higher in the ischaemic (10 min and 30 min) than the control hearts, 0.22 +/- 0.09 and 0.21 +/- 0.08 versus 0.41 +/- 0.12 and 0.49 +/- 0.11 pmol 10(6) cells, respectively (p < .05, p < .001. The inositol trisphosphate was higher in control than ischemic hearts (10 min, 30 min), 0.42 +/- 0.02 and 0.39 +/- 0.01 versus 0.31 +/- 0.01 and 0.23 +/- 0.02 (percent of radioactivity) respectively, p < .001. Our data suggest that 3H-inositol may be studied by i.v. administration to intact animals. The ischemia was performed to verify the validity of this new technique.

[Neuroendocrine response to anesthesia with isoflurane]. / La réponse neuro-endocrinienne à l'anesthésie par isoflurane.

The effects during surgery of a new halogenated volatile anaesthetic, isoflurane, on the hypothalamo-hypophyseal-thyroid-suprarenal axis were studied. In fact, it was important to prove whether this new halogenated anaesthetic would provide better protection, for the patient, from surgery and anaesthetic stress compared with other anaesthetic agents in use. The study was carried out in 16 young class ASA I patients who were to undergo appendicectomy. Before and during operation, blood was taken to measure ACTH, cortisol, TSH, T3, T4 and PRL plasma levels. A remarkable increase of PRL, cortisol and T4 plasmatic rate was found, especially at the end of the operation. It was concluded that isoflurane, just like enflurane, did not prevent the increase of PRL, cortisol and T4 that usually takes place during surgery.

Plasma and CSF morphine concentrations after i.m. and epidural administration.

Morphine concentrations in plasma and CSF after i.m. and epidural morphine administration were assayed in patients undergoing surgery of the low abdomen. Morphine concentration in CSF after i.m. administration of this drug is remarkably lower than morphine concentration in plasma. The highest value is attained in CSF after about 90' and is followed by a slow downsloping to lowest values, which were observed 4 hours after drug administration. Kinetics of morphine passage into plasma after epidural administration is similar to that found after i.m. administration. In the latter experimental condition (epidural administration), concentrations of morphine in CSF 30' after administration are markedly lower than those found in plasma. However, 60 min. after epidural administration plasma and CSF morphine concentrations are similar, in particular CSF concentrations are 4 to 8 times higher than those obtained after i.m. administration. Such high levels persist for a long time.

[Prolactin in pathology of the breast. Clinical study ]. / La prolattina nella patologia della mammella. Contributo clinico.

In the last years many Authors on the grounds of clinical and experimental studies have assumed the possibility of a connection between the prolactin and the breast pathology especially the carcionoma. In the present work the Authors give the results of the doses of the prolactin plasmatic basal levels, performed on 122 subjects belonging to 4 different groups: 1) patients with carcinoma of the breast; 2) patients with benign tumors of the breast; 3) patients with fibrocystic breast disease; 4) subjects of control. In patients who have undergone an operation further doses of blood prolactin have been carried out on 5th, 10th, 30th day after operation. On the grounds of such results the Authors propose new hypothesis of work wich will help to clear this problem.

[Behavior of the plasma level of digoxin in the rat in induced experimental hyperreninemia]. / Comportamento del tasso plasmatico di digossina nel ratto in condizioni di iperreninemia sperimentalmente indotta.

PRA, plasma and urine aldosterone levels and plasma digoxin were measured in rats in which digoxin had been administered under conditions of high PRA and high aldosterone levels experimentally induced by administering distilled water load and in rats in which digoxin had been administered without distilled water load. Results show that under conditions of high PRA and high aldosterone levels, plasma digoxin concentrations as measured 6 h after treatment were higher (45,3%) than in rats having received digoxin without water load. In assays carried out on rats sacrificed 12 h after digoxin treatment (with or without water load) all values approach basic levels again, thus suggesting that in rats too aldosterone might compete with digoxin at the level of tubular excretion.