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Garwicz, Daniel
Publications (10 of 28) Show all publications
Venge, P., Douhan Håkansson, L., Garwicz, D., Peterson, C., Xu, S. & Pauksen, K. (2015). Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections. Clinical and Vaccine Immunology, 22(9), 1025-1032
Open this publication in new window or tab >>Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections
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2015 (English)In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 22, no 9, p. 1025-1032Article in journal (Refereed) Published
Abstract [en]

The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P<0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P<0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.

National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-263440 (URN)10.1128/CVI.00347-15 (DOI)000360491000006 ()26135974 (PubMedID)
Available from: 2015-10-07 Created: 2015-09-30 Last updated: 2018-01-11Bibliographically approved
Venge, P., Douhan, L. H., Garwicz, D., Peterson, C., Xu, S. & Pauksen, K. (2015). Human neutrophil lipocalin in fMLP-activated whole blood as a diagnostic means to distinguish between acute bacterial and viral infections. JIM - Journal of Immunological Methods, 424, 85-90
Open this publication in new window or tab >>Human neutrophil lipocalin in fMLP-activated whole blood as a diagnostic means to distinguish between acute bacterial and viral infections
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2015 (English)In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 424, p. 85-90Article in journal (Refereed) Published
Abstract [en]

The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) in serum distinguishes acute infections with high accuracy, but in the emergency setting the assay time should be <15-20 min, which excludes the use of serum samples. The aim was therefore to develop a novel rapid assay principle and test its clinical performance. Methods: Serum and neutrophils obtained from 84 infected and 20 healthy subjects were used in the experimental study. 725 subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the clinical study. HNL was measured in EDTA-plasma by ELISA or in heparinized whole blood after fMLP activation by a prototype point-of-care assay. Results: Increased release of HNL from neutrophils after activation with fMLP was seen already after 5 min incubation. The release of HNL from purified neutrophils after 15 min incubation with fMLP was significantly correlated to the HNL concentrations in serum obtained from the same patient (r = 0.74, p < 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the ROC-curves were 0.95 (95% CI 0.91-0.97) and 0.88 (95% CI 0.84-0.91) for HNL in fMLP-activated whole blood and EDTA-plasma, respectively, (p <0.001) and in the distinction between bacterial and viral infections 0.91 (95% CI 0.86-0.95) and 0.76 (95% CI 0.70-0.81), respectively (p <0.001). Conclusion: The clinical performance of HNL in fMLP-activated whole blood was superior to HNL in EDTA-plasma and similar to HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.

Keywords
Acute infection, Neutrophil, Bacterial infection, Viral infection, Point-of-care, Human neutrophil lipocalin
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-265624 (URN)10.1016/j.jim.2015.05.004 (DOI)000361848900011 ()26002155 (PubMedID)
Available from: 2015-11-04 Created: 2015-11-02 Last updated: 2018-01-10Bibliographically approved
Eriksson, O., Håkansson, L. D., Karawajczyk, M. & Garwicz, D. (2015). Neutrophil CD64 expression - comparison of two different flow cytometry protocols on EPICs MCL and the Leuko64 (TM) assay on a Celldyn Sapphire haematology analyser. Scandinavian Journal of Clinical and Laboratory Investigation, 75(5), 428-433
Open this publication in new window or tab >>Neutrophil CD64 expression - comparison of two different flow cytometry protocols on EPICs MCL and the Leuko64 (TM) assay on a Celldyn Sapphire haematology analyser
2015 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 75, no 5, p. 428-433Article in journal (Refereed) Published
Abstract [en]

Objective. To evaluate the Trillium Diagnostics Leuko64 (TM) assay on Abbott Celldyn Sapphire haematology analyser compared to two flow cytometry protocols on Beckman Coulter EPICS MCL flow cytometer. Materials and methods. CD64 expression on neutrophils was determined by two flow cytometry protocols and by a commercial assay on an automatic haematology analyser. The inclusion of study subjects was based on elevated procalcitonin (PCT) values, identifying patients where a systemic infection was suspected. Healthy blood donors were used as a reference group. Results. Statistically significant correlations between the Trillium Diagnostics Leuko64 (TM) assay and the flow cytometry methods were found when measuring neutrophil CD64 expression. Conclusions. The good correlation between a reference method and an automated haematology analyser method for CD64 expression on neutrophils supports introduction of the latter assay for routine use as an independent biomarker of bacterial infection and inflammation.

Keywords
CD64, flow cytometry, neutrophils, method comparison
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-262972 (URN)10.3109/00365513.2015.1031690 (DOI)000360177600012 ()25874478 (PubMedID)
Available from: 2015-09-23 Created: 2015-09-23 Last updated: 2017-12-01Bibliographically approved
Rögnvaldsson, T., You, L. & Garwicz, D. (2015). State of the art prediction of HIV-1 protease cleavage sites. Bioinformatics, 31(8), 1204-1210
Open this publication in new window or tab >>State of the art prediction of HIV-1 protease cleavage sites
2015 (English)In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 31, no 8, p. 1204-1210Article in journal (Refereed) Published
Abstract [en]

Motivation: Understanding the substrate specificity of human immunodeficiency virus (HIV)-1 protease is important when designing effective HIV-1 protease inhibitors. Furthermore, characterizing and predicting the cleavage profile of HIV-1 protease is essential to generate and test hypotheses of how HIV-1 affects proteins of the human host. Currently available tools for predicting cleavage by HIV-1 protease can be improved.

Results: The linear support vector machine with orthogonal encoding is shown to be the best predictor for HIV-1 protease cleavage. It is considerably better than current publicly available predictor services. It is also found that schemes using physicochemical properties do not improve over the standard orthogonal encoding scheme. Some issues with the currently available data are discussed.

National Category
Other Medical Sciences not elsewhere specified
Identifiers
urn:nbn:se:uu:diva-256139 (URN)10.1093/bioinformatics/btu810 (DOI)000354453700007 ()25504647 (PubMedID)
Available from: 2015-06-22 Created: 2015-06-22 Last updated: 2017-12-04Bibliographically approved
Garwicz, D. & Wadelius, M. (2013). Farmakogenetisk analys kan avslöja risk för statinbiverkningar: [Pharmacogenetic analysis can predict adverse effects of statins]. Läkartidningen, 110(19-20), 951-952
Open this publication in new window or tab >>Farmakogenetisk analys kan avslöja risk för statinbiverkningar: [Pharmacogenetic analysis can predict adverse effects of statins]
2013 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 19-20, p. 951-952Article in journal (Refereed) Published
Abstract [sv]

Mer än var tionde vuxen i Sverige behandlas med statiner. 

Muskelsvaghet, -trötthet och -värk är kända biverkningar. I sällsynta fall ses rabdomyolys, som kan leda till akut njursvikt och någon gång dödsfall. 

Statiners kemiska egenskaper och serumkoncentration påverkar risken för allvarliga biverkningar. Serumkoncentrationen beror på dos och på patientens förmåga att omsätta läkemedlet.

Akademiska sjukhuset har som första svenska sjukhus infört analys av en genetisk variant (SLCO1B1*5) som kan förutsäga ökad risk för sällsynta, allvarliga muskelbiverkningar vid statinbehandling.

National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-222637 (URN)23745502 (PubMedID)
Available from: 2014-04-11 Created: 2014-04-11 Last updated: 2017-12-05
Garwicz, D. & Karlman, M. (2012). Early recognition of reverse pseudohyperkalemia in heparin plasma samples during leukemic hyperleukocytosis can prevent iatrogenic hypokalemia. Clinical Biochemistry, 45(18), 1700-1702
Open this publication in new window or tab >>Early recognition of reverse pseudohyperkalemia in heparin plasma samples during leukemic hyperleukocytosis can prevent iatrogenic hypokalemia
2012 (English)In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 45, no 18, p. 1700-1702Article in journal (Refereed) Published
Abstract [en]

Objectives: To investigate the cause of apparent hyperkalemia in leukemic heparin plasma. Design and methods: Lithium heparin plasma and serum samples from a patient with chronic lymphocytic leukemia (CLL) with hyperleukocytosis were transported by either a pneumatic tube system or manual transport and analyzed either immediately or after 4 h. Results: Pneumatic tube transported samples resulted in higher plasma potassium levels than manually transported samples. Serum potassium was lower than plasma potassium, confirming the suspicion of "reverse" pseudohyperkalemia. Letting the pneumatic tube transported samples stand on the bench for 4 h before centrifugation surprisingly resulted in decreased or unchanged plasma potassium. Conclusions: The reverse pseudohyperkalemia in heparin plasma samples from a CLL patient was caused by pneumatic tube transport. Our results suggest extracellular leakage of potassium, followed by active transport of potassium into intact leukemic cells. This is the first Swedish case of reverse pseudohyperkalemia in a CLL patient, where clinical suspicion of false hyperkalemia and awareness of the phenomenon lead to a rapid laboratory diagnosis. The demonstration of reverse pseudohyperkalemia prevented potentially dangerous medical interventions, such as potassium lowering treatment.

Keywords
Chronic lymphocytic leukemia, Hyperleukocytosis, Plasma, Potassium, Hyperkalemia
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-191035 (URN)10.1016/j.clinbiochem.2012.07.104 (DOI)000312048900033 ()
Available from: 2013-01-09 Created: 2013-01-09 Last updated: 2019-05-02
Garwicz, D., Karlman, M. & Øra, I. (2011). Reverse pseudohyperkalemia in heparin plasma samples from a child with T cell acute lymphoblastic leukemia with hyperleukocytosis [Letter to the editor]. Clinica Chimica Acta, 412(3-4), 396-397
Open this publication in new window or tab >>Reverse pseudohyperkalemia in heparin plasma samples from a child with T cell acute lymphoblastic leukemia with hyperleukocytosis
2011 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 412, no 3-4, p. 396-397Article in journal, Letter (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-149042 (URN)10.1016/j.cca.2010.10.023 (DOI)000287115400034 ()21056034 (PubMedID)
Available from: 2011-03-15 Created: 2011-03-15 Last updated: 2017-12-11
Rögnvaldsson, T., Etchells, A., You, L., Garwicz, D., Jarman, I. & Lisboa, P. J. G. (2009). How to find simple and accurate rules for viral protease cleavage specificities. BMC Bioinformatics, 10, 149
Open this publication in new window or tab >>How to find simple and accurate rules for viral protease cleavage specificities
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2009 (English)In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 10, p. 149-Article in journal (Refereed) Published
Abstract [en]

Background: Proteases of human pathogens are becoming increasingly important drug targets, hence it is necessary to understand their substrate specificity and to interpret this knowledge in practically useful ways. New methods are being developed that produce large amounts of cleavage information for individual proteases and some have been applied to extract cleavage rules from data. However, the hitherto proposed methods for extracting rules have been neither easy to understand nor very accurate. To be practically useful, cleavage rules should be accurate, compact, and expressed in an easily understandable way. Results: A new method is presented for producing cleavage rules for viral proteases with seemingly complex cleavage profiles. The method is based on orthogonal search-based rule extraction (OSRE) combined with spectral clustering. It is demonstrated on substrate data sets for human immunodeficiency virus type 1 (HIV-1) protease and hepatitis C (HCV) NS3/4A protease, showing excellent prediction performance for both HIV-1 cleavage and HCV NS3/4A cleavage, agreeing with observed HCV genotype differences. New cleavage rules (consensus sequences) are suggested for HIV-1 and HCV NS3/4A cleavages. The practical usability of the method is also demonstrated by using it to predict the location of an internal cleavage site in the HCV NS3 protease and to correct the location of a previously reported internal cleavage site in the HCV NS3 protease. The method is fast to converge and yields accurate rules, on par with previous results for HIV-1 protease and better than previous state-of-the-art for HCV NS3/4A protease. Moreover, the rules are fewer and simpler than previously obtained with rule extraction methods. Conclusion: A rule extraction methodology by searching for multivariate low-order predicates yields results that significantly outperform existing rule bases on out-of-sample data, but are more transparent to expert users. The approach yields rules that are easy to use and useful for interpreting experimental data.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-128400 (URN)10.1186/1471-2105-10-149 (DOI)000267595400003 ()
Available from: 2010-07-23 Created: 2010-07-20 Last updated: 2017-12-12
Carlsson, G., Boxhammer, S., Garwicz, D., Henter, J. I., Palmblad, J., Nordenskjöld, M., . . . Fadeel, B. (2009). Survivin expression in the bone marrow of patients with severe congenital neutropenia [Letter to the editor]. Leukemia, 23(3), 622-625
Open this publication in new window or tab >>Survivin expression in the bone marrow of patients with severe congenital neutropenia
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2009 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 23, no 3, p. 622-625Article in journal, Letter (Refereed) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-102841 (URN)10.1038/leu.2008.258 (DOI)000264032600032 ()18818705 (PubMedID)
Available from: 2009-05-12 Created: 2009-05-12 Last updated: 2017-12-13Bibliographically approved
Melin, M., Entesarian, M., Carlsson, G., Garwicz, D., Klein, C., Fadeel, B., . . . Dahl, N. (2007). Assignment of the gene locus for severe congenital neutropenia to chromosome 1q22 in the original Kostmann family from Northern Sweden. Biochemical and Biophysical Research Communications - BBRC, 353(3), 571-575
Open this publication in new window or tab >>Assignment of the gene locus for severe congenital neutropenia to chromosome 1q22 in the original Kostmann family from Northern Sweden
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2007 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 353, no 3, p. 571-575Article in journal (Refereed) Published
Abstract [en]

Autosomal recessive severe congenital neutropenia (SCN) or Kostmann syndrome is characterised by reduced neutrophil counts and subsequent recurrent bacterial infections. The disease was originally described in a large consanguineous pedigree from Northern Sweden. A genome-wide autozygosity scan was initiated on samples from four individuals in the original pedigree using high density single nucleotide polymorphism (SNP) genotyping arrays in order to map the disease locus. Thirty candidate regions were identified and the ascertainment of samples from two additional patients confirmed a single haplotype with significant association to the disorder (p < 0.01) on chromosome 1q22. One affected individual from the original Kostmann pedigree was confirmed as a phenocopy. The minimal haplotype shared by affected individuals spans a candidate region of 1.2 Mb, containing several potential candidate genes.

Keywords
Homozygosity mapping, Kostmann syndrome, Severe congenital neutropenia, SNP array
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-15937 (URN)10.1016/j.bbrc.2006.12.086 (DOI)000243570000008 ()17188649 (PubMedID)
Note
Publikation i samarbete med annat universitetAvailable from: 2008-06-18 Created: 2008-06-18 Last updated: 2017-12-08Bibliographically approved
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