Rapid drop in serum testosterone after bilateral subcapsular orchiectomy.

Bilateral subcapsular orchiectomy was performed in six patients with metastatic prostatic carcinoma. In these patients the serum levels of testosterone were determined serially up to twenty-four hours. Castrate levels of testosterone were achieved in about two and one-half hours. This is the first published report of such a rapid decrease in serum testosterone. Castrate levels of serum testosterone using the luteinizing hormone releasing hormone (LH-RH) agonists are achieved in fourteen to twenty-one days. The relative cost of orchiectomy and LH-RH agonists, for thirty-six months, was $2,042.00 and $12,780.00, respectively. LH-RH agonists may be effective for only a year. Urologists are urged to continue using bilateral subcapsular orchiectomy and not use LH-RH agonists in the management of metastatic prostatic carcinoma.     

Molecular approach to the nucleo-melanosomal interaction in human melanoma cells

This paper presents evidence that L-tyrosine oxidation products and 5,6-dihydroxyindole, an intermediate of melanin synthesis bind to and modify DNA structure, as tested by extracting cell DNA, using topoisomerase I and denaturation assays. When supercoiled plasmid pCU18 or pBR322 DNAs are treated with 5,6-dihydroxyindole the supercoiled species disappear and are converted to species less mobile in a gel retardation test with respect to relaxed DNA. 5,6-Dihydroxyindole causes an easier acid denaturation of the double helix. The results, that are dose dependent,would point to both intercalation and cross-linking of DNA by 5,6-dihydroxyindole and its oxidation product(s). ³H-L-tyrosine deriving radioactivity, bound to nuclear DNA, is higher at low pH, (5.6) if compared to pH 6.8. The highest radioactivity bound to cell DNA is found during the transition from the amelanotic to the melanotic phenotype in human melanoma cell lines. As a control, the binding of ³H-L-tyrosine radioactivity to human prostate fibroblast DNA was investigated.     

Mast cells in the estrogen-induced transplantable renal tumor of the hamster

Mast cells are frequently seen in and around a variety of malignant tumors. However, mast cells have not been seen in the transplantable estrogen-induced renal tumor of the hamster. In this study the subcutaneously transplanted renal tumor of Kirkman was examined using a variety of fixation techniques. All tissues were stained in toluidine blue (0.5% solution at a pK of 3.8). Mast cells were seen in great numbers only in tumor tissue frozen in isopentane cooled with liquid nitrogen at −155 C and cut on a cryostat at −20C. This would indicate the importance of the method of preparation of such fastidious cells. The hamster tumor provides, then, an excellent source of mast cells for study in a tumor environment.     

Defining the learning outcomes of graduates from the medical school at the University of Barcelona (Catalonia, Spain)

It is generally accepted that medical schools must clearly define learning outcomes for their students. During the process of curriculum change initiated in 1990, Spanish medical schools introduced a range of general objectives but no specific outcomes were defined. In 2001, in an effort to improve its curriculum, the Medical School at the University of Barcelona decided to define the specific learning outcomes for its graduates. The process was carried out by a teachers' group, comprising individuals from different branches of medicine, drawing largely on the Outcome-based Education in Medicine model introduced by the Scottish Deans' Medical Curriculum Group (2000). Other different stakeholders were asked to give any suggestions for modifications in order to prepare a definitive document to be approved by the medical school. The whole process took two years to complete. The authors discuss the advantages of such a process for students, teachers and the institution.     

Lymphocytes genetically modified to express tumor antigens target DCs in vivo and induce antitumor immunity

The exploitation of the physiologic processing and presenting machinery of DCs by in vivo loading of tumor-associated antigens may improve the immunogenic potential and clinical efficacy of DC-based cancer vaccines. Here we show that lymphocytes genetically modified to express self/tumor antigens, acting as antigen carriers, efficiently target DCs in vivo in tumor-bearing mice. The infusion of tyrosinase-related protein 2-transduced (TRP-2-transduced) lymphocytes induced the establishment of protective immunity and long-term memory in tumor-bearing mice. Analysis of the mechanism responsible for the induction of such an immune response allowed us to demonstrate that cross-presentation of the antigen mediated by the CD11c(+)CD8alpha(+) DC subset had occurred. Furthermore, we demonstrated in vivo and in vitro that DCs had undergone activation upon phagocytosis of genetically modified lymphocytes, a process mediated by a cell-to-cell contact mechanism independent of CD40 triggering. Targeting and activation of secondary lymphoid organ-resident DCs endowed antigen-specific T cells with full effector functions, which ultimately increased tumor growth control and animal survival in a therapeutic tumor setting. We conclude that the use of transduced lymphocytes represents an efficient method for the in vivo loading of tumor-associated antigens on DCs.     

Arrhythmias and cardiac electrophysiology

In the past few months, numerous articles have been published on arrhythmias and cardiac electrophysiology. As in previous years, a substantial proportion of researchers have concentrated on atrial fibrillation, both on catheter ablation of chronic and paroxysmal atrial fibrillation and on the development of new approaches to thromboembolism prophylaxis. The feasibility of atrial fibrillation ablation by remote control has been demonstrated and a step-wise approach to ablation has been proposed, which appears to improve outcome and reduce lesion size. In addition, multicenter randomized trials have shown that the improvements in functional class and left ventricular ejection fraction achieved by ablation in patients with chronic atrial fibrillation are greater than those resulting from pharmacological treatment. New strategies are being developed to improve the selection of patients for defibrillator implantation and to decrease the number of high-energy discharges occurring during follow-up. Controlled trials continue to demonstrate that pharmacological therapy is of little value in preventing recurrence of vasovagal syncope compared with maneuvers involving isometric muscular contraction. Finally, one of the most significant events in the last year was the publication of new clinical practice guidelines by European and American societies of cardiology. These provide important recommendations on the treatment and prevention of ventricular arrhythmias and sudden death and on the management of and thromboembolic prophylaxis in atrial fibrillation.     

Retroperitoneal hematoma by different causes: Presentation of two emergency cases at computed tomography

Retroperitoneal hematoma is a rare clinical entity with variable aetiology, which is increasing in incidence mainly due to complications related to interventional procedures. The causes of RE are different. We present 2 suggestive cases of RE, one for renal cause and another of adrenal origin. Both came to our attention as a matter of urgency. Retroperitoneal hematoma, therefore, originated from different causes, with consequent different treatments. Both cases were diagnosed, as a matter of urgency, thanks to the use of contrast Computed Tomography, which allowed a rapid diagnosis, careful specialist evaluation, a monitoring of their clinical conditions, and a consequent adequate outcome for the patients.     

Mutagenicity test for unstable compounds, such as 5,6-dihydroxyindole, using an Escherichia coli HB101/pBR322 transfection system

A mutagenicity test for unstable chemical compounds has been devised. The test makes use of (i) in vitro treatment of plasmid pBR322 with the putative mutagen (ii) subsequent transfection of Escherichia coli HB101; (iii) selection either on tetracycline- or ampicillin-containing Eugon agar (iv) cross-antibiotic replica plating and recovery of single antibiotic resistant colonies (v) restriction analysis of pBR322 isolated from single antibiotic resistant colonies. In this work the test has been used to assess the mutagenicity of 5,6-dihydroxyindole, a cytotoxic intermediate of melanin biosynthesis.