Utilizzo del Rituximab nel trattamento della vasculiti ANCA associate.

Introduzione. Recenti studi hanno dimostrato che il Rituximab (RTX) è un’alternativa sicura ed efficace alla ciclofosfamide nell’indurre la remissione in pazienti con severa vasculite ANCA-associata (AAV) di nuova diagnosi o recidiva. Scopo dello studio era valutare l’efficacia e la sicurezza del RTX nei nostri pazienti con AAV. Metodi. Studio retrospettivo delle caratteristiche cliniche, dei risultati e della tolleranza al RTX dei pazienti con AAV trattati presso il nostro centro da Gennaio 2006 a Dicembre 2011. Inizialmente veniva utilizzato lo schema convenzionale delle 4 somministrazioni settimanali da 375 mg/m2. Dal 2011 sulla base dell’esperienza maturata e dei nuovi dati della letteratura si decideva di non adottare uno schema fisso per le recidive, ma di somministrare una o due dosi secondo la severità della recidiva ed il rischio infettivo. Risultati. Venivano trattati 51 pazienti con AAV, 15/51 (29%) di nuova diagnosi e 36/51 (71%) ad una recidiva. La maggior parte dei pazienti con nuova diagnosi presentavano una micropoliangioite con severo interessamento renale, 5/15 (33%) erano in dialisi dall’esordio. 32/36 (89%) pazienti trattati ad una recidiva presentavano una recidiva granulomatosa di Granulomatosi di Wegener (WG). Tutti ottenevano una remissione, più rapidamente per le manifestazioni vasculitiche. 2/5 pazienti in dialisi dall’esordio recuperavano la funzione renale. Si osservavano 11 recidive in 9 pazienti con GW mediamente dopo 23.1 mesi, tutti ottenevano nuovamente la remissione. Ad un follow-up medio di 20.1 mesi si registravano 4 decessi, 3 (3/15, 20%) nel gruppo di pazienti con nuova diagnosi, uno (1/36, 3%) nel gruppo trattato ad una recidiva. Quattro pazienti sospendevano il RTX per infezioni. Conclusioni. Nella nostra casistica il RTX si è dimostrato efficace e sicuro nell’indurre la remissione in pazienti con severa AAV, sia all’esordio che alla recidiva. I pazienti con WG presentano maggior rischio di recidiva e dovrebbero pertanto essere mantenuti in terapia immunosoppressiva dopo RTX.

Induction Motor Diagnosis in Variable Speed Drives

Several diagnostic techniques are presented for the detection of electrical fault in induction motor variable speed drives. These techinques are developed taking into account the impact of the control system on machine variables and non stationary operating conditions.

Grid Connected Doubly Fed Induction Generator Based Wind Turbine under LVRT

This project concentrates on the Low Voltage Ride Through (LVRT) capability of Doubly Fed Induction Generator (DFIG) wind turbine. The main attention in the project is, therefore, drawn to the control of the DFIG wind turbine and of its power converter and to the ability to protect itself without disconnection during grid faults. It provides also an overview on the interaction between variable speed DFIG wind turbines and the power system subjected to disturbances, such as short circuit faults. The dynamic model of DFIG wind turbine includes models for both mechanical components as well as for all electrical components, controllers and for the protection device of DFIG necessary during grid faults. The viewpoint of this project is to carry out different simulations to provide insight and understanding of the grid fault impact on both DFIG wind turbines and on the power system itself. The dynamic behavior of DFIG wind turbines during grid faults is simulated and assessed by using a transmission power system generic model developed and delivered by Transmission System Operator in the power system simulation toolbox Digsilent, Matlab/Simulink and PLECS.

In vitro characterisation and expansion of human regulatory T cells for their in vivo application in the induction of tolerance in haematopoietic stem cell and solid organ transplantation

Solid organ transplantation (SOT) is considered the treatment of choice for many end-stage organ diseases. Thus far, short term results are excellent, with patient survival rates greater than 90% one year post-surgery, but there are several problems with the long term acceptance and use of immunosuppressive drugs. Hematopoietic Stem Cells Transplantation (HSCT) concerns the infusion of haematopoietic stem cells to re-establish acquired and congenital disorders of the hematopoietic system. The main side effect is the Graft versus Host Disease (GvHD) where donor T cells can cause pathology involving the damage of host tissues. Patients undergoing acute or chronic GvHD receive immunosuppressive regimen that is responsible for several side effects. The use of immunosuppressive drugs in the setting of SOT and GvHD has markedly reduced the incidence of acute rejection and the tissue damage in GvHD however, the numerous adverse side effects observed boost the development of alternative strategies to improve the long-term outcome. To this effect, the use of CD4+CD25+FOXP3+ regulatory T cells (Treg) as a cellular therapy is an attractive approach for autoimmunity disease, GvHD and limiting immune responses to allograft after transplantation. Treg have a pivotal role in maintaining peripheral immunological tolerance, by preventing autoimmunity and chronic inflammation. Results of my thesis provide the characterization and cell processing of Tregs from healthy controls and patients in waiting list for liver transplantation, followed by the development of an efficient expansion-protocol and the investigation of the impact of the main immunosuppressive drugs on viability, proliferative capacity and function of expanded cells after expansion. The conclusion is that ex vivo expansion is necessary to infuse a high Treg dose and although many other factors in vivo can contribute to the success of Treg therapy, the infusion of Tregs during the administration of the highest dose of immunosuppressants should be carefully considered.