104 research outputs found
Influence of opioids on immune function in patients with cancer pain: from bench to bedside
In patients with cancer, opioids are principally used for the management of acute surgical and chronic cancer-related pain. However, opioids have many non-analgesic effects, including direct and indirect effects on cancer cells and on anti-tumour immunity (NK cells, macrophages and T-cells). Direct effects on immune cells are manifested via opioid and non-opioid toll-like receptors, whereas indirect effects are manifested via the sympathetic nervous system and hypothalamicâpituitaryâadrenal axis. Opioids can also decrease/alter immune cell infiltration into the tumour micro-environment. Animal models have shown that this is not a class effect, in that morphine and fentanyl suppress NK cell cytotoxicity; buprenorphine does not affect NK cell cytotoxicity, whereas tramadol increases NK cell cytotoxicity, reducing metastasis. In healthy individuals, morphine suppresses and fentanyl enhances NK cell cytotoxicity. In patients undergoing surgery, fentanyl decreased and tramadol increased NK cell cytotoxicity; clinical outcomes were not determined. Meta-analyses of opioid-sparing surgical studies report an association between improved recurrence-free and/or overall survival with regional/neuraxial anaesthesia compared with systemic opioids. In patients receiving opioids for non-surgical cancer-related pain, morphine has variable effects on immunity; clinical outcomes were not assessed. Although there is a potential association between systemic opioid administration and shorter survival in cancer patients with a prognosis of months to years, studies have not been designed to primarily assess survival, as a consequence of which causality cannot be apportioned. Pain is immunosuppressive, so analgesia is important. Opioids for cancer-related pain will continue to be recommended until definitive data on the effects of opioids on clinical outcomes in specific patient groups becomes available
Education and service : how theories can help in understanding tensions
Acknowledgements: our thanks to Ayelet Kuper for a helpfuldiscussion about the possible application of discourseanalysis to serviceâtraining tensionsPeer reviewedPostprin
CodeâSwitching Pedagogies and African American Student Voices: Acceptance and Resistance
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88094/1/JAAL.53.2.3.pd
Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice
Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals,
there are two converging apoptosis pathways: the âextrinsicâ pathway, which is triggered by engagement of cell surface âdeath
receptorsâ such as Fas/APO-1; and the âintrinsicâ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival
and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic
proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To
investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1
transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional
Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the
macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was
striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells
(TCRÎČ+
CD4â
CD8â
B220+
) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr
mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating
autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene
by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell
population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the
development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other
haemopoietic cell types
Embracing Wobble: Exploring Novice Teachersâ Efforts to Enact Dialogic Literacy Instruction
Incidence and causes of perioperative mortality after primary surgery for intracranial tumors: a national, population-based study
Intensity and features of acute postoperative pain after mastectomy and breast-conserving surgery
In-hospital mortality after surgery: a retrospective cohort study in a Japanese university hospital
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