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Östermalm, Sweden

Wang Y.,Lund University | Braun O.O.,Lund University | Zhang S.,Lund University | Norstrom E.,Section of Clinical Chemistry | Thorlacius H.,Lund University
Biochemical and Biophysical Research Communications | Year: 2015

Sepsis causes severe derangements of the coagulation system. However, the signaling mechanisms regulating sepsis-induced thrombin generation remain elusive. Herein, we hypothesized that Rho-kinase might be an important regulator of thrombin generation in abdominal sepsis. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57Bl/6 mice. Thrombin generation, coagulation factors, lung histology and myeloperoxidase (MPO) activity were determined 6 h and 24 h after induction of CLP. Induction of CLP triggered a systemic inflammatory response characterized by neutrophil accumulation and tissue injury in the lung as well as thrombocytopenia and leukocytopenia. Administration of Y-27632, a Rho-kinase inhibitor, attenuated these markers of systemic inflammation in CLP animals. Moreover, peak thrombin formation was decreased by 77% and 81% in plasma from mice 6 h and 24 h after induction of CLP. Total thrombin generation was reduced by 64% and 67% 6 h and 24 h after CLP induction, respectively. Notably, administration of Y-27632 increased peak formation by 99% and total thrombin generation by 66% in plasma from septic animals. In addition, CLP markedly decreased plasma levels of prothrombin, factor V and factor X at 6 h and 24 h. Interestingly, Rho-kinase inhibition significantly enhanced levels of prothrombin, factor V and factor X in plasma from septic mice. In addition, inhibition of Rho-kinase decreased CLP-induced elevations of CXCL2 by 36% and interleukin-6 by 38%. These novel findings suggest that sepsis-induced thrombin generation is regulated by Rho-kinase. Moreover, inhibition of Rho-kinase reverses sepsis-evoked consumption of coagulation factors. Thus, our results show that targeting Rho-kinase signaling might protect against coagulation dysfunction in abdominal sepsis. © 2015 Elsevier Inc. All rights reserved.

Mindemark M.,Section of Clinical Chemistry | Wernroth L.,Uppsala Clinical Research Center | Larsson A.,Section of Clinical Chemistry
Scandinavian Journal of Clinical and Laboratory Investigation | Year: 2010

Objective: Laboratory tests are used increasingly in primary health care and they are thus associated with rapidly growing costs. Variations in clinical practice, an important determinant of expenditure for laboratory tests, could further increase the financial burden. The study's threefold objective was to determine the presence and extent of regional variations in test ordering between eight counties in Sweden, to investigate the influence on these variations by factors earlier described in the literature as explanatory, and to calculate the achievable savings that could be realized through optimized test ordering. Design: A retrospective study using test request data. Setting: A total of 223 primary health care centers in eight counties in Sweden. Main outcome measures: Thirteen ratios of commonly used laboratory tests, demographic data and the number of ordered tests per 1000 inhabitants served as the basis of comparison. The total savings per 100,000 inhabitants that could be achieved through optimized test ordering was estimated. Results: Large variations were found between all studied counties for all investigated ratios. However, none of the demographic variables investigated seemed to be able to explain the full extent of the variations. The range of achievable yearly savings per 100,000 inhabitants was €14,000€185,000. Conclusion: The inter-county variations in Sweden are large and the savings associated with optimized test utilization are substantial. The investigated factors previously described as explaining the variations in test ordering only seem to explain a small part of the variation, and the variations are likely influenced by regional habits and traditions. © 2010 Informa UK Ltd.

Farahnak P.,Section of Surgery | Farahnak P.,Karolinska Institutet | Larfars G.,Section of Internal Medicine | Larfars G.,Karolinska Institutet | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: The extent and clinical significance of cardiovascular (CV) abnormalities associated with mild primary hyperparathyroidism (PHPT) are still matters for discussion. Objective: The main objective of the present study was to evaluate biochemical CV risk markers in PHPT patients before and after parathyroidectomy (PTX) in comparison with controls. Design and Subjects: In a prospective case-control design, 49 patients with PHPT and 49 healthy matched controls were included. Methods: Blood pressure (BP), 25-OH-D, plasminogen activator inhibitor-1 activity, von Willebrand factor antigen, homocysteine, high-sensitivity C-reactive protein, IGF-I, and lipid profile were evaluated at baseline and 15 ± 4 months after PTX. Results: At baseline, the level of 25-OH-D was significantly lower in patients compared with controls (40.1 ± 16.5 vs. 64.6 ± 20.8 nmol/liter, P < 0.001) and increased after PTX (58.9 ± 19.5, P < 0.001). Postoperatively, 25-OH-D was inversely correlated to the PTH level (r = -0.34; P < 0.05). Systolic BP (127.2 ± 17.4 vs. 119.3 ± 12.5mmHg, P < 0.05) and triglyceride (TG; 1.04 ± 0.60 vs. 0.86 ± 0.43 mmol/liter, P < 0.05) were higher in patients compared with controls and decreased slightly in patients after PTX (BP, 124.4 ± 16.8mmHg, and TG, 0.94 ± 0.50 mmol/liter, P < 0.05). Otherwise, there were no intergroup differences in coagulation, inflammatory, metabolic, and lipid status. Conclusions: Except for a lower 25-OH-D level and slightly higher systolic BP and TG levels, patients with mild PHPT without other CV risk factors did not differ from healthy controls as regards biomarkers predicting CV diseases. PTX had an overall positive effect on TG level, BP, and vitamin D status. Copyright © 2011 by The Endocrine Society.

Mindemark M.,Section of Clinical Chemistry | Larsson A.,Section of Clinical Chemistry
Clinical Biochemistry | Year: 2012

Objectives: To estimate the possible economic effects of a sequential testing strategy with F-calprotectin to minimize colonoscopies. Design and methods: Retrospective study in a third party payer perspective. The costs were calculated from initial F-calprotectin test results of 3639 patients. Two cut-off levels were used: 50 μg/g feces and 100 μg/g feces, respectively. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for colonoscopies. Results: The estimated demand for colonoscopies was reduced by 50% with the 50 μg/g cut-off and 67% with the 100 μg/g cut-off. This corresponded to a cost avoidance of approximately €1.57. million and €2.13. million, respectively. Conclusions: The use of F-calprotectin as a screening test substantially could reduce the number of invasive measurements necessary in the diagnostic work-up of patients with suspected IBD, as well as the associated costs. © 2011.

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