Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups

The most effective post-remission treatment to maintain complete remission (CR) in adults aged between 46 and 60 years with acute myeloid leukaemia (AML) is uncertain. Previously untreated patients with AML in CR after induction chemotherapy with daunorubicin and cytarabine were randomized between two intensive courses of consolidation therapy containing high-dose cytarabine, combined with amsacrine or daunorubicin and a standard consolidation and maintenance therapy containing standard dose cytarabine and daunorubicin. One hundred fifty-eight CR patients were assigned to the intensive group and 157 patients to the standard group. After a median follow-up of 7.5 years, the 4-year survival rate was 32 % in the intensive group versus 34 % in the standard group (P = 0.29). In the intensive group, the 4-year relapse incidence was lower than in the standard group: 55 and 75 %, respectively (P = 0.0003), whereas treatment-related mortality incidence was higher: 22 versus 3 % (P < 0.0001). Two intensive consolidation courses containing high-dose cytarabine as post-remission treatment in patients with AML aged between 46 and 60 years old did not translate in better long-term outcome despite a 20 % lower relapse incidence. Better supportive care and prevention of treatment-related complications may improve the overall survival after intensified post-remission therapy in this age group

ATP release via anion channels

ATP serves not only as an energy source for all cell types but as an ‘extracellular messenger-for autocrine and paracrine signalling. It is released from the cell via several different purinergic signal efflux pathways. ATP and its Mg2+ and/or H+ salts exist in anionic forms at physiological pH and may exit cells via some anion channel if the pore physically permits this. In this review we survey experimental data providing evidence for and against the release of ATP through anion channels. CFTR has long been considered a probable pathway for ATP release in airway epithelium and other types of cells expressing this protein, although non-CFTR ATP currents have also been observed. Volume-sensitive outwardly rectifying (VSOR) chloride channels are found in virtually all cell types and can physically accommodate or even permeate ATP4- in certain experimental conditions. However, pharmacological studies are controversial and argue against the actual involvement of the VSOR channel in significant release of ATP. A large-conductance anion channel whose open probability exhibits a bell-shaped voltage dependence is also ubiquitously expressed and represents a putative pathway for ATP release. This channel, called a maxi-anion channel, has a wide nanoscopic pore suitable for nucleotide transport and possesses an ATP-binding site in the middle of the pore lumen to facilitate the passage of the nucleotide. The maxi-anion channel conducts ATP and displays a pharmacological profile similar to that of ATP release in response to osmotic, ischemic, hypoxic and salt stresses. The relation of some other channels and transporters to the regulated release of ATP is also discussed

y+ LAT-1 mediates transport of the potent and selective iNOS inhibitor, GW274150, in control J774 macrophages

The original publication is available at www.springerlink.com--Copyright Springer --DOI : 10.1007/s00726-005-0311-9Peer reviewe

High Frequency Properties of Josephson Junctions

In this chapter we will discuss the high frequency properties of Josephson junctions. In the first part we review the effect of a large ac perturbation on the current voltage characteristic (IVC) of a Josephson junction. Here we follow closely the original treatment by Barone and Paterno [1]. For large ac perturbations the externally applied microwave frequency (and integer multiples of it) lock to the Josephson oscillation causing distinct current steps at fixed voltage values in the IVC. In the second part we give a short overview on the response of an underdamped\ua0Josephson junction to small microwave perturbations. In this case, when the applied microwave frequency is in resonance with the electromagnetic plasma frequency\ua0higher levels of this plasma mode get excited. This mechanism, also called resonant activation, leads for instance to a premature switching from the zero voltage state to the finite voltage state of a current biased Josephson junction. This procedure can be exploited to detect the quantized nature, i.e. the quantized energy levels, of the plasma modes. In fact the lowest two quantized energy levels\ua0of the plasma resonance mode are the key ingredient of superconducting qubits, such as the phase qubit\ua0and the transmon qubit

Quantitative Methods, Applications, and Trends in Asian Tourism Research

This chapter states the purpose and goals of the entire book covering the status and future directions of quantitative tourism research in Asia. As an introductory part, this chapter describes the scope of the book and provides a brief explanation and summary of chapters. As such, this chapter highlights the research paradigm, philosophy and design, and other quantitative-specific dimensions before intruding on each chapter. The chapters of the book are divided into 3 main parts including understanding tourism industry in Asia (Part I), the current status of quantitative techniques (Part II), and future directions for Asian tourism researches (Part III). In fact, the introduction chapter implicitly discusses how tourism context might be different from the other settings and argues that the creation of knowledge even in quantitative data analysis to some extent is context dependent. Therefore, this chapter discusses an overview of data analysis strategies that is often overlooked by researchers

Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients.

A large proportion of adult patients with acute myeloid leukemia (AML) relapse after treatment, and some of them are resistant to primary induction chemotherapy. Sixty-one patients from seven hematological centers with poor-risk AML, primary refractory (n = 16), or relapsed (n = 45) were treated with a salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a sequential continuous infusion, associated with liposomal daunorubicin (3 days) (FLAD). Complete response rate was 44% and 56% for refractory and relapsed patients, respectively, with an overall response rate of 52% (32 of 61). Twenty-two patients (36%) were resistant to the salvage therapy. Seven patients (12%) died early during chemotherapy, four of them because of sepsis. Nineteen patients in complete remission (CR) underwent a stem-cell transplant (SCT) procedure: five autologous, nine from a HL-A identical sibling, and five from HL-A matched unrelated donors. Post-treatment aplasia and mucositis were major toxicities. Twenty patients (62.5%) relapsed after this treatment in a median of 7.3 months; ten patients relapsed after a SCT procedure. Nine patients are alive and disease free; three of them were rescued after a further cytotoxic treatment. The FLAD regimen proved to be an effective and well-tolerated treatment, with acceptable toxicity in this group of high-risk patients. A better response rate was obtained in the subgroup of relapsed patients, compared to patients treated for refractory disease. More then half (five of nine) of long-surviving patients are those who were submitted to a transplant procedure; thus, the main indication for FLAD seems to be to try to induce a rapid CR with minimum toxicity in order to perform a transplant as soon as possible