| 1. |
- Aeinehband, Shahin, et al.
(författare)
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Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.
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| 2. |
- Lindblom, Rickard P. F., et al.
(författare)
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Complement receptor 2 is up regulated in the spinal cord following nerve root injury and modulates the spinal cord response
- 2015
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094 .- 1742-2094. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of the complement system has been implicated in both acute and chronic states of neurodegeneration. However, a detailed understanding of this complex network of interacting components is still lacking. Methods: Large-scale global expression profiling in a rat F2(DAxPVG) intercross identified a strong cis-regulatory influence on the local expression of complement receptor 2 (Cr2) in the spinal cord after ventral root avulsion (VRA). Expression of Cr2 in the spinal cord was studied in a separate cohort of DA and PVG rats at different time-points after VRA, and also following sciatic nerve transection (SNT) in the same strains. Consequently, Cr2(-/-) mice and Wt controls were used to further explore the role of Cr2 in the spinal cord following SNT. The in vivo experiments were complemented by astrocyte and microglia cell cultures. Results: Expression of Cr2 in naive spinal cord was low but strongly up regulated at 5-7 days after both VRA and SNT. Levels of Cr2 expression, as well as astrocyte activation, was higher in PVG rats than DA rats following both VRA and SNT. Subsequent in vitro studies proposed astrocytes as the main source of Cr2 expression. A functional role for Cr2 is suggested by the finding that transgenic mice lacking Cr2 displayed increased loss of synaptic nerve terminals following nerve injury. We also detected increased levels of soluble CR2 (sCR2) in the cerebrospinal fluid of rats following VRA. Conclusions: These results demonstrate that local expression of Cr2 in the central nervous system is part of the axotomy reaction and is suggested to modulate subsequent complement mediated effects.
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| 3. |
- Lindblom, Rickard P. F., et al.
(författare)
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Dissecting ventricular pseudoaneurysm after perimyocarditis : a case report
- 2015
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The current case describes the fast development of a pseudoaneurysm in a patient that presented with signs of systemic inflammation and generally deranged blood work. Case Presentation: The pseudoaneurysm appeared within one week of disease onset. The anatomic extent of the pseudoaneurysm was unusual, as it dissected intramurally beneath the septum, inferior to the right ventricle and had effect on the RV filling. The etiology could not be definitely defined, since in adults the most common cause for pseudoaneurysm development is recent myocardial infarction, but in this patient the coronary arteries were healthy. Instead it could have been a consequence of an aggressive perimyocarditis. Conclusions: Due to the unpredictable nature of pseudoaneurysms we advocate early contact with a center with cardiothoracic surgery expertise for rapid surgical intervention.
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| 4. |
- Lindblom, Rickard P F, et al.
(författare)
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Outcomes following the implementation of a quality control campaign to decrease sternal wound infections after coronary artery by-pass grafting
- 2015
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261 .- 1471-2261. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coronary artery by-pass grafting (CABG) remains the optimal strategy in achieving complete revascularization in patients with complex coronary artery disease. However, sternal wound infections (SWI), especially deep SWI are potentially severe complications to the surgery. At the department of cardiothoracic surgery in Uppsala University Hospital a gradual increase in all types of SWI occurred, which peaked in 2009. This prompted an in-depth revision of the whole surgical process. To monitor the frequency of post-operative infections all patients receive a questionnaire that enquires whether any treatment for wound infection has been carried out.METHODS: All patients operated with isolated CABG between start of 2006 and end of 2012 were included in the study. 1515 of 1642 patients answered and returned the questionnaire (92.3 %). The study period is divided into the time before the intervention program was implemented (2006-early 2010) and the time after the intervention (early 2010- end 2012). To assess whether potential differences in frequency of SWI were a consequence of change in the characteristics of the patient population rather than an effect of the intervention a retrospective assessment of medical records was performed, where multiple of the most known risk factors for developing SWI were studied.RESULTS: We noticed a clear decrease in the frequency of SWI after the intervention. This was not a consequence of a healthier population.CONCLUSIONS: Our results from implementing the intervention program are positive in that they reduce the number of SWI. As several changes in the perioperative care were introduced simultaneously we cannot deduce which is the most effective.
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| 5. |
- Lytsy, Birgitta, 1968-, et al.
(författare)
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Hygienic interventions to decrease deep sternal wound infections following coronary artery bypass grafting
- 2015
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Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701 .- 1532-2939. ; 91:4, s. 326-331
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The department of Cardiothoracic Surgery at Uppsala University Hospital has 25 beds in one to four patient rooms and an operating suite consisting of five operating rooms with ultraclean air. Around 700 open heart (250 isolated coronary artery bypass grafting, CABG) operations are performed annually. In 2009, the numbers of deep sternal wound infections (DSWIs) increased to unacceptable rates despite existing hygienic guidelines.AIM: To show how root cause analysis (RCA) followed by quality improvement interventions reduced the rate of DSWI after CABG surgery.METHODS: Only isolated CABG patients requiring surgical revision due to DSWI were included. Swabs and tissue biopsies were taken during surgical revision and analysed with standard methods. DSWIs were registered prospectively according to US Centers for Disease Control and Prevention definitions. RCA for infection was performed between September 2009 and April 2010. Interventions based on results of the RCA and on nationally recommended practices were concluded in April 2010, and thought to have taken full effect by July 1st, 2010. Air was actively sampled at ≤0.5m from the sternal incision.FINDINGS: DSWI incidence rates per CABG operations decreased from 5.1% pre intervention to 0.9% post intervention. Wound cultures pre intervention grew Staphylococcus aureus 27.1% and coagulase negative staphylococcus (CoNS) 47.1%, post intervention S. aureus 23.1% and CoNS 30.8%. Air counts did not exceed 5cfu/m(3).CONCLUSION: When the aetiology of an error is multifactorial, RCA engaging both the medical professions and the infection control team is a potential tool to map causes leading to adverse events such as healthcare-associated infections. A systematic quality improvement intervention based on the RCA may reduce the number of deep sternal wound infections after CABG surgery.
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