Timed sequential chemotherapy with concomitant Granulocyte Colony-Stimulating Factor for high-risk acute myelogenous leukemia: a single arm clinical trial

BACKGROUND: The timed-sequential chemotherapy regimen consisting of etoposide, mitoxantrone and cytarabine (EMA) is an effective therapy for relapsed or refractory acute myelogenous leukemia (AML). We postulated that granulocyte colony-stimulating factor (G-CSF) might enhance the cytotoxicity of EMA by increasing the proportion of leukemic blasts in S-phase. We added G-CSF to EMA (EMA-G) for therapy of advanced high-risk AML patients. METHODS: High-risk AML was defined as refractory, relapsed or secondary to either an antecedent hematologic disorder or exposure to cytotoxic agents. The patients were treated with one course of EMA-G consisting of mitoxantrone and cytarabine on days 1–3, and etoposide and cytarabine on days 8–10. G-CSF was started on day 4 and continued until absolute neutrophil count recovered. RESULTS: Thirty patients were enrolled. The median age was 51 years (range, 25–75). Seventeen (61%) patients had unfavorable cytogenetic karyotypes. Twenty (69%) patients had secondary AML. Ten (34%) had relapsed disease. Four (14%) had refractory AML. Three (10%) patients died from febrile neutropenia and sepsis. Major non-hematologic toxicity included hyperbilirubimenia, renal insufficiency, mucositis, diarrhea, nausea and vomiting, skin rash. A complete remission was achieved in 13 (46%) patients. Median overall survival was 9 months (range, 0.5–66). Median relapse-free survival (RFS) for those who had a CR was 3 months (range, 0.5–63) with RFS censored at the time of allogeneic bone marrow transplantation or peripheral stem cell transplantation for 6 of the patients. CONCLUSIONS: EMA-G is a safe and efficacious option for induction chemotherapy in advanced, high-risk AML patients. The activity of EMA may be increased if applied in patients with less advanced disease

Kinome Profiling Reveals an Interaction Between Jasmonate, Salicylate and Light Control of Hyponastic Petiole Growth in Arabidopsis thaliana

Plants defend themselves against infection by biotic attackers by producing distinct phytohormones. Especially jasmonic acid (JA) and salicylic acid (SA) are well known defense-inducing hormones. Here, the effects of MeJA and SA on the Arabidopsis thaliana kinome were monitored using PepChip arrays containing kinase substrate peptides to analyze posttranslational interactions in MeJA and SA signaling pathways and to test if kinome profiling can provide leads to predict posttranslational events in plant signaling. MeJA and SA mediate differential phosphorylation of substrates for many kinase families. Also some plant specific substrates were differentially phosphorylated, including peptides derived from Phytochrome A, and Photosystem II D protein. This indicates that MeJA and SA mediate cross-talk between defense signaling and light responses. We tested the predicted effects of MeJA and SA using light-mediated upward leaf movement (differential petiole growth also called hyponastic growth). We found that MeJA, infestation by the JA-inducing insect herbivore Pieris rapae, and SA suppressed low light-induced hyponastic growth. MeJA and SA acted in a synergistic fashion via two (partially) divergent signaling routes. This work demonstrates that kinome profiling using PepChip arrays can be a valuable complementary ∼omics tool to give directions towards predicting behavior of organisms after a given stimulus and can be used to obtain leads for physiological relevant phenomena in planta

Client–nurse Relationships in Home-based Palliative Care: A Critical Analysis of Power Relations

Aim: To elicit an in-depth understanding of the sources of power and how power is exercised within client–nurse relationships in home-based palliative care. Background: As in all social relations, power is present within client–nurse relationships. Although much research has focused on interpersonal relationships in nursing, the concept of power within the client–nurse relationship in palliative care settings has not been extensively investigated. Methods: Applying a critical lens, secondary qualitative data analysis was conducted. Seventeen nurse and 16 client transcripts from a primary study were selected for secondary data analysis. These 33 transcripts afforded theme saturation, which allowed for both commonalities and differences to be identified. Data analysis involved analytic coding. Results: Study findings help make explicit the underlying power present in the context of home-based palliative care and how this power is used and potentially abused. In analysing the sources and exercise of power, the linkage between macro and micro levels of power is made explicit, as nurses functioned within a hierarchy of power. The findings suggest that educational/occupational status continues to be a source of power for nurses within the relationship. However, nurses also experience powerlessness within the home care context. For clients, being able to control one\u27s own life is a source of power, but this power is over-shadowed by the powerlessness experienced in relationships with nurses. The exercise of power by clients and nurses creates experiences of both liberation and domination. Conclusions: Nurses who are willing to reflect on and change those disempowering aspects of the client-nurse relationship, including a harmful hierarchy, will ultimately be successful in the health promotion of clients in home-based palliative care. Additionally, it should be recognized that nurses work within a specific health system context and, therefore, their practice is influenced by policies and funding models implemented at various levels of the health care system. Relevance to clinical practice: The insights gained through this investigation may assist nurses and other health professionals in reflecting on and improving practices and policies within home-based palliative care and within home care in general