Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission

Background: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor. Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life. Results: A total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P<0.001). Median relapse-free survival was also significantly longer with CC-486 than with placebo (10.2 months and 4.8 months, respectively; P<0.001). Benefits of CC-486 with respect to overall and relapse-free survival were shown in most subgroups defined according to baseline characteristics. The most common adverse events in both groups were grade 1 or 2 gastrointestinal events. Common grade 3 or 4 adverse events were neutropenia (in 41% of patients in the CC-486 group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during CC-486 treatment. Conclusions: CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in remission after chemotherapy. Side effects were mainly gastrointestinal symptoms and neutropenia. Quality-of-life measures were maintained throughout treatment

Satisfacción en pacientes con reconstrucción mamaria con colgajo D.I.E.P. Patient’s satisfaction after diep flap reconstruction

La reconstrucción mamaria tras mastectomía se realiza primordialmente para proporcionar calidad de vida a la paciente. Este estudio se desarrolló para valorar la satisfacción y calidad de vida de las pacientes reconstruidas mediante colgajo D.I.E.P. (Deep Inferior Epigastric Perforator) y evaluar el resultado estético de la reconstrucción. Treinta y tres pacientes, de 51 reconstrucciones mamarias con colgajo DIEP realizadas entre enero de 2000 y noviembre de 2004 fueron preguntadas acerca de aspectos generales relativos a la cirugía, imagen corporal y sensación subjetiva. El resultado de imagen corporal fue evaluado por dos observadores externos, un cirujano plástico y una enfermera, además de por la propia paciente. Para valorar la reconstrucción mamaria, se utilizó una escala de 4 puntos. La satisfacción general de nuestro estudio fue más elevada que la observada en estudios precedentes. Hemos conseguido una valoración alta en simetría, dentro de los parámetros objetivos y en integridad corporal entre los subjetivos. Hemos encontrado una correlación alta entre las respuestas de los observadores comparada con las respuestas de las propias pacientes. Por último, hemos visto una fuerte correlación entre integridad corporal y satisfacción general<br>Breast reconstructions after breast cancer surgery are primarily performed to improve patient&rsquo;s quality of life. This study investigates patient&rsquo;s satisfaction and quality of life with breast reconstruction after deep inferior epigastric perforator (D.I.E.P.) flap surgery and to evaluate the aesthetic result of the breast reconstruction. Thirty-three patiens, from fifty-one DIEP breast reconstruction made between january 2000 and december 2004 were answered about three questionnaires concerning to general aspect, body image, and subjective sensation. The body image outcome was also evaluated by one plastic surgeon and a nurse. The panel evaluated breast reconstruction on 4 subescales. General satisfaction in our study was higher than in previous ones. We have received a high degree of symmetry in the objetive evaluation and a high score in body integrity in the subjective evaluation. We have found a stronger correlation between clinical observer answers compared with patient&acute;s assessment and a strong correlation between body integrity and general satisfaction outcom

A new role of AMP-activated protein kinase in regulating proliferation of mesenchymal stem cells

Purpose: Natriuretic peptides (NPs) administered during early reperfusion are protective in models of myocardial infarction. A previous study examining the endogenous components of B-type natriuretic peptide (BNP) protection of reperfused myocardium, implicated both sarcolemmal (s) KATP and mitochondrial (m) KATP channels. The indirect evidence characterising the relationship between BNP signalling and KATP was obtained using sulphonylurea receptor inhibitors in a rat isolated heart model of ischaemia-reperfusion injury. Here we seek to further examine the relationship between NPs and sKATP openings using single channel electrophysiology. Given our previous findings and the overarching consensus that cardioprotective autacoids open KATP channels, it was hypothesised that NPs elicit sKATP opening. Methods: Cardiomyocyte isolation. Left ventricular cardiomyocytes were isolated from male Sprague-Dawley rat hearts subjected to enzymatic digestion with Liberase Blendzyme DL. Cardiomyocytes were cultured overnight in Medium 199, prior to patch clamp. Single channel patch clamp. Single channel recordings at room temperature (22°C) were made from cell attached patches bathed in Na+ Locke, pH 7.2. The recording pipette contained high KCl (140 mM), pH 7.2. Recordings (45 sec) were made over a range of patch potentials (0, -30, -60, -90, -120 mV), in the absence (control) and in the presence of bath applied BNP (10, 100 nM and 1 µM), pinacidil (200 µM) or pinacidil vehicle (DMSO, 0.25%). Recordings were also made with BNP and pinacidil applied concomitantly. Data are mean ± S.E.M. Results: The current voltage relationship of sKATP under control conditions was linear at –ve patch potentials, the mean conductance being 52.9 ± 1.8 pS (n = 18 hearts, n = 35 cells). Pinacidil caused a four fold increase in sKATP open probability compared to control. Mean channel conductance in the presence of pinacidil was 59.9 ± 1.9 pS (n = 16 hearts, n = 44 cells). Interestingly BNP at all concentrations had negligible effects on sKATP open probability and unitary conductance. However, BNP at all concentrations and patch potentials inhibited pinacidil induced sKATP openings, restoring channel open probability to baseline. Conclusion: These data illustrate the inhibitory effect of NP signalling on sKATP function in the cardiomyocyte under normoxia. They are concordant with the inhibitory effect of atrial NP on KATP in the pancreatic beta cell, but are in apparent conflict with the current cardioprotection paradigm. However, differential effects on sKATP and mKATP and the effects of hypoxia-reoxygenation require further exploration