Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas.

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas

Practical Experience Report: Implementation, verification and validation of a safe and secure communication protocol for the railway domain

Different communication protocols are currently being used for the railway domain. However, most of these protocols rely on many interlacing mechanisms and safety codes which raise their complexity. Therefore, companies operating in the railway domain, guided by the Italian railway network manager, devised the Protocollo Vitale Standard, a light network protocol that stems from the Euroradio and RBC-RBC (Radio Block Centre) protocols. In this paper we report our practical experience in the implementation of the Protocollo Vitale Standard in compliance with a CENELEC SIL4 safety target. The implementation of this protocol required assembling a V&V&S plan to specify all the V&V activities that need to be carried out before, during and after the implementation of the protocol. Moreover, coding styles, standards and code quality metrics are defined, and cross-checked at various stages of the implementation. To complete our work, we conducted tests and performance analyses on the source code, while currently we are devising an adequate safety case aiming at a future certification

Development and validation of a safe communication protocol compliant to railway standards

Railway systems are composed of a multitude of subsystems, sensors, and actuators that exchange datagrams through safety-critical communication protocols. However, the vast majority of these protocols rely on ad hoc interlacing mechanisms and safety codes which raise the heterogeneity and complexity of the overarching railway system. Therefore, Rete Ferroviaria Italiana, the company who is in charge of managing the Italian railway network, coordinated the definition of the Protocollo Vitale Standard (Standard Vital Protocol). This protocol is inspired to, and compliant with, the communication protocols adopted for the European Train Control System (ETCS) (SUBSET, UNISIG, 037, Euroradio FIS, version 2.3. 0; SUBSET, UNISIG, 098, RBC-RBC safe communication interface, 2007), and it is meant to become the standard layer to enable safe communication between components of the Italian railway system. This paper reports our experience in the design, implementation, verification, and validation of the Protocollo Vitale Standard in compliance with the European safety standards for railway systems. We first defined a safety plan and a verification and validation plan, which guide the design, development, verification, and validation activities as required by safety standards. Guidelines of such plans have been followed strictly until completion of the work, which concludes with the provision of a safety case where all safety evidences are summarized. Noticeably, we (i) selected appropriate safety mechanisms, (ii) verified the software design, (iii) implemented the software in compliance with code metrics and coding rules, (iv) conducted tests to validate the protocol against its functional and performance requirements, and ultimately (v) devised all relevant documentation and a safety case which summarizes the evidences needed for certification

R115777 (Zarnestra((R)))/Zoledronic acid (Zometa((R))) cooperation on inhibition of prostate cancer proliferation is paralleled by Erk/Akt inactivation and reduced Bcl-2 and bad phosphorylation

Zoledronic acid (ZOL) has proved activity in bone metastases from prostate cancer through inhibition of mevalonate pathway and of prenylation of intracellular proteins. We have reported that ZOL synergizes with R115777 farnesyltransferase inhibitor (FTI, Zarnestra) in inducing apoptosis and growth inhibition on epidermoid cancer cells. Here, we have studied the effects of the combination of these agents in prostate adenocarcinoma models and, specifically, on androgen-independent (PC3 and DU145) and -dependent (LNCaP) prostate cancer cell lines. We have found that ZOL and R115777 were synergistic in inducing both growth inhibition and apoptosis in prostate adenocarcinoma cells. These effects were paralleled by disruption of Ras→Erk and Akt survival pathways, consequent decreased phosphorylation of both mitochondrial bcl-2 and bad proteins, and caspase activation, Finally, ZOL/R115777 combination induced cooperative effects also in vivo on tumor growth inhibition of prostate cancer xenografts in nude mice with a significant survival increase. These effects were paralleled by enhanced apoptosis and inactivation of both Erk and Akt. In conclusions, the combination between ZOL and FTI leads to enhanced anti-tumor activity in human prostate adenocarcinoma cells likely through a more efficacious inhibition of ras-dependent survival pathways and consequent bcl-related proteins-dependent apoptosis. © 2006 Wiley-Liss, Inc

Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) LAL0201-B protocol.

Thirty elderly (> 60 years) Philadelphia chromosome\u2013positive (Ph ) patients with acute lymphoblastic leukemia (ALL) received imatinib, 800 mg daily, associated to steroids without further chemotherapy as frontline treatment. Median age was 69 years (range, 61-83 years). Twenty-nine patients were evaluable for response and all of them obtained a hematologic complete remission, with a median BCR-ABL reduction of 2.9 and 2.0 logs in p190 and p210 cases, respectively. Most of the induction treatment did not require admission of the patients. No major toxicities occurred and the treatment was well tolerated. Median survival from diagnosis was 20 months. This study shows that elderly Ph patients with ALL\u2014often considered eligible only for palliative treatment strategies\u2014 may benefit from an imatinibsteroids protocol, which does not require chemotherapy nor a long hospitalization, is feasible, highly active, and associated with a good quality of lif