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- Neerland, B. E., et al.
(författare)
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Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial
- 2022
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status. Methods and analysis This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 mu g/kg/hour. The infusion rate will be decreased to 0.2 mu g/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first. Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery. Ethics and dissemination This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings.
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- Richardsen, E., et al.
(författare)
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The prognostic impact of M-CSF, CSF-1 receptor, CD68 and CD3 in prostatic carcinoma
- 2008
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 53:1, s. 30-38
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Macrophage colony-stimulating factor (M-CSF) binds to colony-stimulating factor-1 receptor (CSF-1R) and stimulates proliferation and differentiation of monocytes, macrophages and their bone marrow progenitors. M-CSF, CSF-1R, the macrophage marker CD68, and the pan T-lymphocyte marker CD3 are increased in many human cancers. Their prognostic importance in primary prostatic carcinoma has not been fully delineated. The aim was to compare the expression of M-CSF, CSF-1R, CD68 and CD3 in metastatic and non-metastatic prostatic cancer. Methods and results: Digital video analysis of tumour cell areas and tumour stromal areas was performed in 59 cancer specimens: 32 patients with metastases and 27 patients without metastases. Expression of M-CSF and CSF-1R was recorded as 0 (negative immunoreactivity), 1 (weak), 2 (moderate) or 3 (strong reactivity). Macrophages (CD68) and T lymphocytes (CD3) were detected as proportions of moderately or strongly immunoreactive cells. Patients with metastatic primary cancers showed higher expression of M-CSF (P < 0.0001, P = 0.005), CSF-1R (both P < 0.0001) and CD3 (P = 0.007, P < 0.0001) in both tumour cell areas and tumour stromal areas, compared with the non-metastatic cancers. Conclusions: This study suggests that expression of M-CSF, CSF-1R and CD3 is a significant prognostic factor in primary prostatic cancers by predicting the development of metastases.
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