PubMed · 15150368
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
Yi Zhang, Mae Thamer, Kevin Stefanik, Dennis J Cotter. 2004. Does dose matter?. https://doi.org/10.1093/ndt%2Fgfh233
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Intravenous Fe is widely used to treat anemia in renal disease patients. However, concerns of potential Fe toxicity exist. To more fully define its spectrum, this study tested Fe's impact on systemic inflammation following either endotoxemia or the induction of direct tissue damage (glycerol-mediated rhabdomyolysis). The inflammatory response was gauged by tissue TNF-alpha message expression and plasma TNF-alpha levels. CD-1 mice received either intravenous Fe sucrose, -gluconate, or -dextran (FeS, FeG, or FeD, respectively; 2 mg), followed by either endotoxin (LPS) or glycerol injection 0-48 h later. Plasma TNF-alpha was assessed by ELISA 2-3 h after the LPS or glycerol challenge. TNF-alpha mRNA expression (RT-PCR) was measured in the kidney, heart, liver, lung, and spleen with Fe +/- LPS treatment. Finally, the relative impacts of intramuscular vs. intravenous Fe and of glutathione (GSH) on Fe/LPS- induced TNF-alpha generation were assessed. Each Fe preparation significantly enhanced LPS- or muscle injury-mediated TNF-alpha generation. This effect was observed for at least 48 h post-Fe injection, a time at which plasma iron levels were increased by levels insufficient to fully saturate transferrin. Fe did not independently increase plasma TNF-alpha or tissue mRNA. However, it potentiated postinjury-induced TNF-alpha mRNA increments and did so in an organ-specific fashion (kidney, heart, and lung; but not in liver or spleen). Intramuscular administration, but not GSH treatment, negated Fe's ability to synergize LPS-mediated TNF-alpha release. We conclude 1) intravenous Fe can enhance TNF-alpha generation during LPS- or glycerol-induced tissue damage; 2) increased TNF-alpha gene transcription in the kidney, heart, and lung may contribute to this result; and 3) intramuscular administration, but not GSH, might potentially mitigate some of Fe's systemic toxic effects.
OBJECTIVE: To review the use of erythropoietin for anemia in heart failure (HF). DATA SOURCES: Peer-reviewed articles in MEDLINE (1966-June 2004) were identified and citations from available articles were reviewed using the search terms anemia, erythropoietin, and heart failure. DATA SYNTHESIS: Anemia worsens HF prognosis. Clinical studies in patients with New York Heart Association Class III/IV HF who had hemoglobin <12 mg/dL and were refractory to maximal medical management showed that erythropoietin improves symptoms. Larger scale studies with mortality endpoints are required to confirm the benefits. CONCLUSIONS: In selected patients with severe, chronic HF, erythropoietin may be considered for functional improvement. However, routine use of this treatment strategy is not recommended until more data are available.
BACKGROUND: Anemia in patients with cancer causes fatigue, weakness, and impaired concentration, negatively impacting quality of life (QOL). In clinical trials involving patients with cancer who had varied characteristics, it has been shown that epoetin alfa treatment increased hemoglobin levels and improved QOL. A systematic review and metaanalysis of data from those trials was conducted to summarize existing knowledge on the role of epoetin alfa in improving QOL for anemic patients with cancer. METHODS: The Cochrane Library and other data bases were searched for published and unpublished, randomized/controlled and single-arm studies that included > or = 20 patients with cancer per arm, epoetin alfa treatment, and QOL assessment by Cancer Linear Assessment Score (CLAS), Functional Assessment of Cancer Therapy (FACT) scale, Eastern Cooperative Oncology Group (ECOG) scale, and/or Medical Outcomes Study Short-Form 36 (SF-36) scale. RESULTS: Among 11,459 patients from 23 trials, epoetin alfa and control cohorts were indistinguishable (with regard to demographic, clinical, QOL variables) at baseline. Epoetin alfa improved CLAS (20-25%), FACT-Fatigue (17%), and FACT-Anemia (12%) scores (P = 0.05). ECOG scores worsened for control cohorts (P = 0.05); epoetin alfa cohorts remained unchanged. Four of the SF-36 subscales, Physical Function, Role Physical, Vitality, and Social Function, improved with epoetin alfa (P = 0.05). Results adjusted for confounding factors remained consistent. CONCLUSIONS: This metaanalysis confirmed that epoetin alfa improves QOL significantly in patients with cancer, emphasizing the need to manage anemia in this population.