Studies of the mode of action of antitumour triazenes and triazines-III. Metabolism studies on hexamethylmelamine

These is good evidence that the antitumour agent hexamethylmelamine (HMM) undergoes oxidative metabolic activation which might occur in the liver and/or extrahepatically. The hepatic microsomal N-methylmelamine metabolizing enzymes were investigated in mice and exhibited different affinities for different melamine derivatives. The apparent Km values are 0.09 mM for HMM, 0.23 mM for pentamethylmelamine, 0.91 mM for 2,2,4,6-tetramethylmelamine and 1.7 mM for trimethylmelamine. HMM inhibited its own metabolism in vitro at substrate concentrations greater than 0.05 mM. Its hepatic microsomal N-demethylation rate was reduced when the mice were pretreated with the hepatic glutathione depleting agent methyliodide. Injection of hexaethylmelamine, a derivative of HMM without antineoplastic properties against the M5076 sarcoma in mice, lead to plasma concentrations of drug and metabolite pentaethylmelamine which were only a fraction of the drug and metabolite levels achieved after a similar dose of HMM.     

Steroid biosynthesis in vitro by the gonads of Sparus auratus L. (Teleostei) at different stages during natural sex reversal

The metabolism in vitro of pregnenolone-4-¹⁴C by the gonads of Sparus auratus L., a protandrous hermaphroditic teleost, was studied during sexual maturity in the male and female phases and during sex reversal. Steroids were identified by their mobilities on thin-layer chromatograms, derivative formation, and recrystallization to constant specific activity, and their yield-time curves were plotted. Progesterone and 17α-hydroxyprogesterone were in every case the most abundant metabolites isolated, and the only ones identified in incubates with ovarian tissue during sex reversal. Some androstenedione was produced by mature testicular tissue, testicular tissue during reversal, and mature ovarian tissue, but only in the first case was there a significant further conversion to testosterone. Although estrogen production was always very small, estradiol-17β and estrone were isolated. Their formation was greater in mature ovarian tissue than in testicular preparations. The gonadal steroids of Sparus auratus L. do not seem to differ from those already described in various gonochoristic species. During sex reversal, gonadal steroid biosynthesis is probably at a minimum, with little interaction between the coexisting testicular and ovarian tissues.     

Evaluation of fitness for work: the most challenging situations

Evaluation of fitness for work (FW) is the final task of both health surveillance and risk evaluation. It's aim is to protect the physical and psychological health of workers and respect their professional skills. The Occupational Physician faces several difficulties in the evaluation of FW. Moreover, Italian legislation on this topic can be variously interpreted and this can cause conflicting evaluations. In this session, the most challenging situations in FW evaluation will be taken into consideration.     

Sutureless and stapleless laparoscopic splenectomy using radiofrequency

Background Bleeding is the main complication and cause of conversion during laparoscopic splenectomy (LS). We present the advantages of the LigaSure vessel sealing system added to the lateral approach for achieving safe vascular control. Methods We performed 63 consecutive LS in a 3-year period using LigaSure in two affiliated university hospitals. We employed a right semilateral position technique with dissection of the spleen and vessel sealing using LigaSure. Forty-two patients had benign hematological disease, 19 had malignant disease, and two had splenic cysts. Results A total of 58 LS were completed with five conversions due to hilar bleeding (three cases), difficult dissection (one), and massive splenomegaly (one). In all but five patients, blood loss was less than 100 ml. No transfusions were needed. There were five postoperative complications: portal thrombosis (one case), hemoperitoneum (two), surgical wound infection (one), and pleural effusion (one). Conclusions The use of LigaSure, and the semilateral position, results in a gain of time and safety. Furthermore, average intraoperative bleeding is very low. Paper presented in part at the 13th European Association for Endoscopic Surgery (EAES) Congress, Venice, Italy, June 2005     

Bilateral renal mass suggestive of cancer

We present the case of a 44-year old man, presenting with acute left flank pain and gross haematuria, affected by bilateral renal mass and massive para-aortic and mediastinic lymphadenopathy, highly suspicious for metastatic renal cancer.     

Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation

OBJECTIVE: To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP. PATIENTS AND METHODS: The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from < or = 6 to > or = 7 or from 7 to > or = 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading. RESULTS: Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%. CONCLUSION: Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options.