345 research outputs found

    Fulminant hyperpyrexia induced by bleomycin

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    Mild and self-limiting fever following bleomycin use is common, and a fatal hyperpyrexial response occurs rarely. In previously reported cases, such hyperpyrexia occurred either after the initial administration of the drug or during subsequent therapy following an initial pyrexial response. We describe a fatal hyperpyrexial reaction after bleomycin in a patient with T-cell lymphoma who had had no febrile response when she received her initial injection 3 weeks earlier. Since the occurrence of this hyperpyrexial response is unpredictable, health care workers as well as patients and relatives should always be alert to this potentially lethal complication and prompt measures should be taken in any patient who develops fever after bleomycin use.published_or_final_versio

    Handbook for Aboriginal Alcohol and Drug Work

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    The Handbook for Aboriginal Alcohol and Drug Work is a practical tool written for Aboriginal drug and alcohol workers, mental health workers and others working in this field. It offers a detailed look at alcohol and drug work from clinical, through to prevention, early intervention and harm reduction. This handbook is also likely to help people working to improve policy and those advocating for change. The idea for it came from workers all over Australia. They told us that they needed an easy to use handbook that can help them respond to the range of alcohol and drug issues they face every day. They also told us that such a book needs to take into account the complex challenges facing workers when helping clients, their families and, sometimes, whole communities

    Expression analysis of the TAB2 protein in adult mouse tissues

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    Background: The Interleukin-1 (IL-1) signaling component TAK1 binding protein 2 (TAB2) plays a role in activating the NFÎșB and JNK signaling pathways. Additionally, TAB2 functions in the nucleus as a repressor of NFÎșB-mediated gene regulation. Objective: To obtain insight into the function of TAB2 in the adult mouse, we analyzed the in vivo TAB2 expression pattern. Materials and methods: Cell lines and adult mouse tissues were analyzed for TAB2 protein expression and localization. Results: Immunohistochemical staining for TAB2 protein revealed expression in the vascular endothelium of most tissues, hematopoietic cells and brain cells. While TAB2 is localized in both the nucleus and the cytoplasm in cell lines, cytoplasmic localization predominates in hematopoietic tissues in vivo. Conclusions: The TAB2 expression pattern shows striking similarities with previously reported IL-1 receptor expression and NFÎșB activation patterns, suggesting that TAB2 in vivo is playing a role in these signaling pathways

    Novel strategies for targeting innate immune responses to influenza.

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    We previously reported that TLR4(-/-) mice are refractory to mouse-adapted A/PR/8/34 (PR8) influenza-induced lethality and that therapeutic administration of the TLR4 antagonist Eritoran blocked PR8-induced lethality and acute lung injury (ALI) when given starting 2 days post infection. Herein we extend these findings: anti-TLR4- or -TLR2-specific IgG therapy also conferred significant protection of wild-type (WT) mice from lethal PR8 infection. If treatment is initiated 3 h before PR8 infection and continued daily for 4 days, Eritoran failed to protect WT and TLR4(-/-) mice, implying that Eritoran must block a virus-induced, non-TLR4 signal that is required for protection. Mechanistically, we determined that (i) Eritoran blocks high-mobility group B1 (HMGB1)-mediated, TLR4-dependent signaling in vitro and circulating HMGB1 in vivo, and an HMGB1 inhibitor protects against PR8; (ii) Eritoran inhibits pulmonary lung edema associated with ALI; (iii) interleukin (IL)-1ÎČ contributes significantly to PR8-induced lethality, as evidenced by partial protection by IL-1 receptor antagonist (IL-1Ra) therapy. Synergistic protection against PR8-induced lethality was achieved when Eritoran and the antiviral drug oseltamivir were administered starting 4 days post infection. Eritoran treatment does not prevent development of an adaptive immune response to subsequent PR8 challenge. Overall, our data support the potential of a host-targeted therapeutic approach to influenza infection
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