| 1. |
- Arnestad, J P, et al.
(författare)
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Isolated hyperthermic liver perfusion with cytostatic-containing perfusate activates the complement cascade.
- 1992
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Ingår i: The British journal of surgery. - 0007-1323. ; 79:9, s. 948-51
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Tidskriftsartikel (refereegranskat)abstract
- Eight patients with advanced liver malignancy undergoing isolated hyperthermic liver perfusion with melphalan and cisplatin were studied with regard to complement activation and formation of anaphylatoxins (C3a and C5a) and terminal C5b-9 complement complexes (TCCs). Blood samples for complement variables (C1-INH, C3, C4, C5, C3a, C5a and TCCs) were taken before surgery, 1 min before the start of perfusion, 1, 2 and 3 h after the start of perfusion, and 24 h after operation. Samples were drawn from the perfusate 1 h after the start of perfusion. Activation of complement was observed during perfusion. Raised plasma concentrations of C3a and TCCs were recorded and high levels of C3a and TCCs were found in the perfusate. In vitro tests indicated that melphalan and cisplatin may activate complement. This activation occurred at 37 and 42 degrees C but was more pronounced at 42 degrees C.
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| 2. |
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| 3. |
- Andersson, Iréne, et al.
(författare)
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Complement split products and pro-inflammatory cytokines in salvaged blood after hip and knee arthroplasty.
- 2001
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Ingår i: Canadian journal of anaesthesia = Journal canadien d'anesthésie. - 0832-610X. ; 48:3, s. 251-5
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine whether salvaged autologous blood collected postoperatively contains complement split products (SC5b-9), and pro-inflammatory cytokines (IL-6 and IL-8) and whether there are any differences between blood collected during hip or knee surgery. METHODS: Fifty-eight consecutive patients undergoing hip or knee replacement surgery were studied. Thirty-eight had postoperative bleeding large enough to require infusion of salvaged blood. The salvaged blood was filtered during collection through a 200 microm filter and before infusion a 40 microm filter was used. Samples for complement and cytokine determinations were drawn from the circulation and from the collected blood. RESULTS: High concentrations of SC5b-9, IL-6, and IL-8 were found in salvaged blood. The concentrations were higher than in the circulation (P < 0.05). The circulating concentrations of IL-6 and IL-8 were increased 60 min and 12-18 hr after transfusion. There were no differences regarding SC5b-9, IL-6, and IL-8 in the blood collected after hip or knee surgery. CONCLUSION: Blood collected from a surgical wound contains large concentrations of inflammatory mediators. There were no differences between blood collected during hip or knee surgery.
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| 4. |
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| 5. |
- Arnestad, J P, et al.
(författare)
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Formation of cytokines by retransfusion of shed whole blood.
- 1994
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Ingår i: British journal of anaesthesia. - 0007-0912. ; 72:4, s. 422-5
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Tidskriftsartikel (refereegranskat)abstract
- We have studied, in 10 patients undergoing hip replacement surgery, the release of cytokines (tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-alpha), interleukin-1 beta (IL-1 beta), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in association with retransfusion of autologous shed blood. The patients were reinfused with whole blood collected after operation. The median volume returned to the patients was 300 ml whole blood (25-75% range = 300-425 ml). Before reinfusion, blood was filtered. Plasma concentrations of IL-6 increased 1 and 60 min after retransfusion (P < 0.05). The plasma concentrations of TNF-alpha, IL-1 alpha, IL-1 beta, IL-4 and IL-8 did not change significantly after retransfusion of shed wound blood. However, there were increased concentrations of IL-1 alpha, IL-1 beta, IL-6 and IL-8 in the collected blood (P < 0.001). The filtration procedure did not reduce significantly the concentrations of these factors. This study shows that whole blood collected from a surgical wound contains large concentrations of cytokines. Filtration of the shed wound blood did not reduce significantly these levels and retransfusion caused increased plasma concentrations of IL-6.
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| 6. |
- Arnestad, J P, et al.
(författare)
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Removal of activated complement from shed blood: comparison of high- and low-dilutional haemofiltration.
- 1998
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Ingår i: Acta anaesthesiologica Scandinavica. - 0001-5172. ; 42:7, s. 811-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Perioperative blood salvage is associated with release of inflammatory mediators. Depending on type of processing, the complement system is activated to some extent in the final blood product. The aim of the present study was to evaluate a haemofiltration technique concerning complement system activation and whether the volume of added saline will have an influence on the elimination of activated complement during processing. METHODS: Sixteen patients undergoing total hip arthroplasty received wound blood salvaged intraoperatively with a haemofiltration technique. Saline was added to the reservoir for washing in a ratio of 1:1 or 5:1 of estimated blood volume. Samples for determination of the anaphylatoxins C3a and C5a, and the terminal SC5b-9 complement complex (TCC) were drawn from the patients, the collected blood, the ultrafiltrate and the processed blood. RESULTS: Increased concentrations of C3a, C5a and TCC were found in aspirated and processed blood. Haemofiltration did not reduce the concentrations of these factors, except that of C3a in the group where saline was added in a ratio of 5:1. There were no increased concentrations of C3a, C5a or TCC in the patient plasma after reinfusion. No differences in blood pressure, heart rate, pH, arterial oxygen tension, arterial carbon dioxide tension, or base excess were found in association with reinfusion of the blood. CONCLUSION: Collected shed blood washed through haemofiltration contained moderately elevated concentrations of C3a, C5a and TCC. Reinfusion of the blood neither led to increased systemic concentrations of complement activation products, nor to disturbances in haemodynamic or biochemical parameters.
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| 7. |
- Bengtsson, Anders, 1954, et al.
(författare)
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Effects on complement activation of a new continuous autotransfusion system.
- 1997
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Ingår i: Transfusion medicine (Oxford, England). - 0958-7578. ; 7:2, s. 107-13
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic blood transfusions may subject patients to risks of infection and allergic reactions. Various techniques for transfusion of shed blood have been developed. The aim of this study was to evaluate a new continuous autotransfusion system (Fresenius CATS) as regards its impact on the complement system, and on erythrocytes and leucocytes. Eighteen consecutive patients undergoing hip replacement surgery were studied. Complement variables (C4d, factor Bb, C3a and terminal complement complex, SC5b-9) and free haemoglobin, haemoglobin, leucocytes, platelets, albumin and protein were determined in the patient's blood preoperatively, 1 min before the start of transfusion, 15 and 60 min after transfusion; and in the reservoir, in the waste bag and in the retransfusion blood. Increased concentrations of C3a and SC5b-9 were found in the collected reservoir blood (P < 0.05). The washing and centrifugation procedure reduced these concentrations (< 0.001). High levels of free haemoglobin were found in the collected blood as well as in the processed product. The median haemoglobin level in the processed blood was 260gL-1 (range 104-289gL-1). Inflammatory mediators from the complement cascade are removed by continuous autotransfusion technique. The processed blood contains high levels of free haemoglobin.
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| 8. |
- Glimelius, Bengt, et al.
(författare)
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Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx®) : a placebo-controlled randomised phase II study (PLIANT)
- 2018
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 57:3, s. 393-402
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC).Patient and methods: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m2, 5-fluorouracil bolus 400 mg/m2, oxaliplatin 85 mg/m2 and 5-fluorouracil 2400 mg/m2 continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible. Calmangafodipir was given in a phase I dose-finding and in a phase II placebo-controlled study, as a 5-min infusion 10 min prior to oxaliplatin. Neurotoxicity was evaluated by the physician using the Oxaliplatin Sanofi Specific Scale and by the patient using the cold allodynia test and the Leonard scale.Results: Eleven patients were included in phase I without any detectable toxicity to calmangafodipir. In the phase II study, 173 patients were randomised to placebo (n = 60), calmangafodipir 2 µmol/kg (n = 57) and calmangafodipir 5 µmol/kg (n = 45, initially 10 µmol/kg, n = 11). Calmangafodipir-treated patients (all three doses pooled) had less physician graded neurotoxicity (odds ratio (90% confidence interval one-sided upper level) 0.62(1.15), p = .16), significantly less problems with cold allodynia (mean 1.6 versus 2.3, p < .05) and significantly fewer sensory symptoms in the Leonard scale (cycle 1–8 mean 1.9 versus 3.0, p < .05 and during follow-up after 3 and 6 months, mean 3.5 versus 7.3, p < .01). Response rate, progression-free and overall survival did not differ among groups.Conclusions: Calmangafodipir at a dose of 5 µmol/kg appears to prevent the development of oxaliplatin-induced acute and delayed CIPN without apparent influence on tumour outcomes.
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| 9. |
- Hyllner, Monica, 1964, et al.
(författare)
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Complement activation in prestorage leucocyte-filtered plasma.
- 2004
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Ingår i: Transfusion medicine (Oxford, England). - : Wiley. - 0958-7578 .- 1365-3148. ; 14:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- Complement activation and generation of pro-inflammatory cytokines occur during storage of blood components. Prestorage leucocyte filtration of platelet concentrates and red cells diminishes the accumulation of leucocyte-derived cytokines during storage, however, transfusion reactions are not eliminated. We investigated inflammatory mediator release during storage of plasma and whole blood and the effect of prestorage leucocyte filtration of plasma. Twenty-four blood units were collected from healthy blood donors and stored for 35 days. Eight units were stored as whole blood, eight units as plasma and eight units as prestorage filtered plasma. Samples were collected weekly for analyses of potassium, leucocytes, free plasma haemoglobin, complement activation (C3a and SC5b-9) and pro-inflammatory cytokines [interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha]. Elevated levels of C3a and SC5b-9 were registered in filtered plasma, from the beginning of storage. C3a levels increased during storage. There was a higher rate of change during storage in C3a (P < 0.01) and SC5b-9 (P < 0.05) in plasma compared with filtered plasma. Interleukin (IL)-8 is released in whole blood. The cytokine levels generated in plasma and filtered plasma were low. Complement activation is present in whole blood, plasma and filtered plasma during storage. Prestorage filtration of plasma activates the complement cascade but does not influence cytokine generation.
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| 10. |
- Kvarnström, Andreas, 1978, et al.
(författare)
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Complement activation and interleukin response in major abdominal surgery
- 2012
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Ingår i: Scandinavian journal of immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 75:5, s. 510-516
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Tidskriftsartikel (refereegranskat)abstract
- Study Objective: The objective of this study was to evaluate whether major abdominal surgery leads to complement activation and interleukin response and whether the kind of anaesthesia influence complement activation and the release of inflammatory interleukins. Design: Prospective and randomised trial. Setting: Operating room and in the postoperative recovery area. Patients: Fifty patients undergoing open major colo-rectal surgery due to cancer disease or inflammatory bowel disease were studied. Interventions: Twenty-five patients were given total intravenous anaesthesia (TIVA) with propofol and remifentanil and 25 were given inhalational anaesthesia with sevoflurane and fentanyl. Measurements: In order to determine complement activation (C3a and SC5b-9) and the release of pro- and anti-inflammatory interleukins (tumour necrosis factor-α (TNF-α)), interleukin-1β (IL-1β), IL-6, IL-8, IL-4 and IL-10) blood samples were drawn pre-operatively, 60 minutes after start of surgery, 30 minutes after end of surgery and 24 hours postoperatively. Main Results: Complement was activated and pro-inflammatory interleukins (IL-6 and IL-8) and anti-inflammatory interleukins (IL-10) were released during major colorectal surgery. There was no significant difference between TIVA and inhalational anaesthesia regarding complement activation and cytokine release. Conclusion: Major colorectal surgery leads to activation of the complement cascade and the release of both pro-inflammatory and anti-inflammatory cytokines. There are no significant differences between total intravenous anaesthesia (TIVA) with propofol and remifentanil and inhalational anaesthesia with sevoflurane and fentanyl regarding complement activation and the release of pro- and anti-inflammatory interleukins.
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