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Thorgersen E.B.,University of Oslo | Hellerud B.C.,University of Oslo | Nielsen E.W.,Nordland Hospital | Nielsen E.W.,University of Tromso | And 9 more authors.
FASEB Journal | Year: 2010

Sepsis is a severe infection-induced systemic inflammatory syndrome. Inhibition of downstream inflammatory mediators of sepsis, e.g., TNF-α, has failed in clinical trials. The aim of this study was to investigate the effects of inhibiting CD14, a key upstream innate immunity molecule, on the early inflammatory and hemostatic responses in a pig model of gram-negative sepsis. The study comprised two arms, whole live Escherichia coli bacteria and E. coli lipopolysaccharide (LPS) (n=25 and n=9 animals, respectively). The animals were allocated into treatment (anti-CD14) and control (IgG isotype or saline) groups. Inflammatory, hemostatic, physiological, and microbiological parameters were measured. The proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8, but not the anti-inflammatory cytokine IL-10, were efficiently inhibited by anti-CD14. Furthermore, anti-CD14 preserved the leukocyte count and significantly reduced granulocyte enzyme matrix metalloproteinase-9 release and expression of the granulocyte membrane activation molecule wCD11R3 (pig CD11b). The hemostatic markers thrombin-antithrombin III complexes and plasminogen activator inhibitor-1 were significantly attenuated. Anti-CD14 did not affect LPS or E. coli DNA levels. This study documents that CD14 inhibition efficiently attenuates the proinflammatory cytokine response and granulocyte activation and reverses the procoagulant state but does not interfere with LPS levels or bacterial counts in E. coli-induced sepsis. © FASEB. Source


Hovland A.,Coronary Care Unit | Hovland A.,University of Tromso | Hardersen R.,Dialysis Unit | Nielsen E.W.,Nordland Hospital | And 5 more authors.
Journal of Clinical Apheresis | Year: 2010

Low density lipoprotein (LDL) apheresis is a long-term treatment and its impact on risk factors other than lipoproteins could be of importance. Three patients with familial hypercholesterolemia participated in six consecutive treatments with three different LDL apheresis columns in random order: DL-75, LA-15, and EC-50W. We compared treatment effects on hemoglobin, leukocytes, platelets, fibrinogen, thrombin-antithrombin complexes (TAT), plasminogen activator inhibitor-1 (PAI-1), and homocysteine. Hemoglobin, leukocytes and platelets decreased significantly with DL-75 (P < 0.05). Hemoglobin and leukocytes increased significantly with LA-15 and EC-50W (P < 0.05). Platelets were unchanged. The DL-75 column was statistically different from LA-15 and EC-50W regarding these parameters. With the columns DL-75, LA-15, and EC-50W fibrinogen decreased significantly by 28%, 32%, and 42%, PAI-1 decreased significantly by 72%, 58%, and 30% while TAT increased significantly by 138%, 3%, and 251%, respectively (P < 0.05 for all). When comparing the columns there were significant differences between all of them regarding fibrinogen, no differences regarding TAT and a difference between DL-75 and EC-50W regarding PAI-1. With the columns DL-75, LA-15 and EC-50W homocysteine decreased 22%, 9%, and 13%, respectively, but there were no inter column differences. In conclusion, the three LDL apheresis columns affected important hematological and hemostatic risk factors differently. Copyright © 2010 Wiley-Liss, Inc. Source


Hovland A.,Nordland Hospital | Hovland A.,University of Tromso | Hardersen R.,Nordland Hospital | Mollnes T.E.,Somatic Research Laboratory | And 3 more authors.
Journal of the Pancreas | Year: 2010

Context Severe hypertriglyceridemia is a known cause of acute pancreatitis, and apheresis treatment, most commonly plasmapheresis, has been used to treat patients with drug refractory hypetriglyceridemia for more than 30 years. Case report We report a case in which a woman with Crohn's disease and type 2 diabetes mellitus developed recurrent episodes of acute pancreatitis due to extreme hypertriglyceridemia. After the initiation of lipoprotein apheresis from whole blood, a marked reduction of triglyceride and lipoprotein levels was observed. Some inflammatory parameters were increased even if most of the cytokines were not detectable, indicating good biocompatibility of the filter. Conclusions Triglyceride levels were lowered after initiating selective lipoprotein apheresis. More importantly, the patient did not experience any relapses of pancreatitis after the treatment was started. Hence this treatment is feasible in drug refractory hypertiglyceridemia, but the treatment concept needs to be tested in additional studies. Source


Hovland A.,Coronary Care Unit | Hovland A.,University of Tromso | Marcovina S.,University of Washington | Hardersen R.,Dialysis Unit | And 5 more authors.
Transfusion and Apheresis Science | Year: 2012

Introduction: High levels of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] are associated with cardiovascular disease. In this study we determined apo(a) particle size and compared the Lp(a) reducing efficacy of three different LDL apheresis columns; DL-75, LA-15 and EC-50W in patients with familial hypercholesterolemia (FH). Results: Average Lp(a) concentration was reduced by 70%, 74% and 75% (all p< 0.0001) for DL-75, LA-15 and EC-50W, respectively. No significant changes in the relative proportion of the isoforms of 14 and 32. K 4 domains were observed after apheresis. Conclusion: Three different LDL apheresis columns reduced Lp(a) efficiently with preserved ratio between apo(a) isoforms. © 2011 Elsevier Ltd. Source


Hovland A.,Coronary Care Unit | Hovland A.,University of Tromso | Hardersen R.,Dialysis Unit | Enebakk T.,Dialysis Unit | And 4 more authors.
Journal of Clinical Lipidology | Year: 2011

Background: Side effects and patient satisfaction in low-density lipoprotein (LDL) apheresis treatment has been less vigorously studied than hemodialysis treatment in end-stage renal failure. Objective: In the present study we systematically compared three different LDL apheresis columns with respect to side effects and patient satisfaction. Methods: Three patients with heterozygous familial hypercholesterolemia went through six treatments with each of the LDL apheresis columns DL-75, LA-15, and EC-50W. Possible side effects were recorded during and after apheresis treatment, and patient satisfaction was assessed by means of a visual analogue scale ranging from 1 to 10. Results: One or several side effects during apheresis were noted in 40%, 29%, and 30% of the treatments for the columns DL-75, LA-15, and EC-50W, respectively. There were no statistically significant differences between the columns. Side effects after apheresis were noted in 33%, 33%, and 18% of the treatments for the columns DL-75, LA-15, and EC-50W, respectively. The latter column was statistically different from the two others. However, general patient satisfaction was high, with visual analogue scale scores of 8.8, 8.7, and 8.9 for DL-75, LA-15, and EC-50W, respectively. Conclusions: Side effects were noted quite frequently during and after LDL apheresis, although significantly there were fewer when the EC-50W column was used after apheresis treatment. Patient satisfaction with the LDL apheresis treatment was high with all columns. © 2011 National Lipid Association. All rights reserved. Source

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