umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Sandqvist, Anna
Publications (10 of 14) Show all publications
Lundgren, J., Sandqvist, A., Hedeland, M., Bondesson, U., Wikström, G. & Rådegran, G. (2018). Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation. Scandinavian Cardiovascular Journal, 52(4), 196-204
Open this publication in new window or tab >>Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation
Show others...
2018 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 4, p. 196-204Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters.

DESIGN: 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation.

RESULTS: In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT.

CONCLUSIONS: Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered "normal" after HT.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
Nitric Oxide, ADMA, L-Arginine, heart transplantation, heart failure, right heart catheterization
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-146983 (URN)10.1080/14017431.2018.1459823 (DOI)000436583700005 ()29648475 (PubMedID)2-s2.0-85045237387 (Scopus ID)
Available from: 2018-04-24 Created: 2018-04-24 Last updated: 2018-09-14Bibliographically approved
Sandqvist, A., Schneede, J., Kylhammar, D., Henrohn, D., Lundgren, J., Hedeland, M., . . . Wikström, G. (2018). Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction. Heart and Vessels, 33(3), 255-263
Open this publication in new window or tab >>Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction
Show others...
2018 (English)In: Heart and Vessels, ISSN 0910-8327, E-ISSN 1615-2573, Vol. 33, no 3, p. 255-263Article in journal (Refereed) Published
Abstract [en]

Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of L-arginine than patients with LVSD (p < 0.05). L-Arginine correlated to 6 min walking distance (6MWD) (r s = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

Keywords
Dimethylarginines, L-Arginine, Left heart failure, Pulmonary arterial hypertension, Systolic dysfunction
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-140337 (URN)10.1007/s00380-017-1055-7 (DOI)000426278900005 ()28975394 (PubMedID)2-s2.0-85030313830 (Scopus ID)
Available from: 2017-10-05 Created: 2017-10-05 Last updated: 2018-06-09Bibliographically approved
Lundgren, J., Sandqvist, A., Hedeland, M., Bondesson, U., Wikstrom, G. & Radegran, G. (2017). L-Arginine and Methylarginines Prior to and After Heart Transplantation. Paper presented at 37th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT), APR 05-08, 2017, San Diego, CA. The Journal of Heart and Lung Transplantation, 36(4), S227-S227
Open this publication in new window or tab >>L-Arginine and Methylarginines Prior to and After Heart Transplantation
Show others...
2017 (English)In: The Journal of Heart and Lung Transplantation, ISSN 1053-2498, E-ISSN 1557-3117, Vol. 36, no 4, p. S227-S227Article in journal, Meeting abstract (Refereed) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-135287 (URN)10.1016/j.healun.2017.01.599 (DOI)000398839800582 ()
Conference
37th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT), APR 05-08, 2017, San Diego, CA
Available from: 2017-05-24 Created: 2017-05-24 Last updated: 2018-06-09Bibliographically approved
Sandqvist, A. (2016). Vardenafil and methylarginines in pulmonary hypertension. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>Vardenafil and methylarginines in pulmonary hypertension
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Pulmonary hypertension (PH) is a rare condition characterized by endothelial dysfunction and vascular remodelling, leading to increased pulmonary vascular resistance (PVR) and right ventricular heart failure. Endothelial dysfunction is associated with an imbalance between vasoconstrictor compounds, such as endothelin and thromboxane A2, and vasodilator compounds, such as prostacyclin and nitric oxide (NO). Asymmetric dimethylarginine (ADMA), a methyl derivate of L-arginine, inhibits synthesis of NO. Vardenafil, a phosphodiesterase type 5 inhibitor (PDE5-inhibitors), causes vasodilation through the NO/cGMP pathway.

Aim: This thesis investigates the pharmacological effects and diagnostic utility of vardenafil in PH patients. In addition, to evaluate the change of L-arginine and dimethylarginines before and during PAHspecific therapy in PAH patients compared to patients with left ventricular heart failure (LVHF) and healthy subjects.

Methods: The pharmacokinetics and hemodynamic effects of vardenafil were examined during right heart catheterization (RHC) in 16 PH patients and plasma concentrations were measured for up to nine hours after oral administration. In 20 PH patients, acute vasoreactivity test with vardenafil was performed during RHC. Hemodynamic responses were recorded, responders were defined and followed for up to seven years. Additionally, plasma ADMA, symmetric dimethylarginine (SDMA), L-arginine, L-citrulline and L-ornithine levels before and after PAH drug treatment were monitored in 21 PAH patients and compared to values measured in 14 LVHF patients and 27 healthy subjects.

Results: Vardenafil concentrations increased rapidly to maximum plasma concentration (tmax 1h) and elimination half-life was 3.4 h. Patients co-medicated with bosentan had reduced vardenafil concentration. Significant acute hemodynamic responses were observed for mean pulmonary artery pressure (mPAP) (p<0.001), pulmonary vascular resistance (PVR) (p<0.001), cardiac output (CO) (p=0.015), cardiac index (CI) (p=0.010), systemic vascular resistance (SVR) (p<0.001) and PVR/SVR (p=0.002) and were related to plasma vardenafil concentrations. PAH patients had significantly higher ADMA and SDMA levels and significantly lower L-arginine levels and L-arginine/ADMA ratio compared with healthy subjects (p<0.001). L-arginine was also lower in PAH patients compared to patients with LVHF (p<0.05). WHO functional class and six minutes walking distance (6MWD) correlated to Larginine and L-arginine/ADMA ratio in PAH at baseline (p<0.05). At follow-up, patients on mono- or combinationtherapy with endothelin receptor antagonists (ERA) had lower ADMA levels than patients without ERA (p<0.05). In contrast, patients on PDE5-inhibitors had higher ADMA levels compared to patients without PDE5-inhibitors (p<0.05).

Conclusion: Vardenafil is safe in acute vasoreactivity test in PH patients. Cardiopulmonary hemodynamic response was related to plasma drug concentrations. There was a high inter-individual variability of vardenafil pharmacokinetics and co-medication with bosentan caused a pharmacokinetic drug interaction. Baseline L-arginine and dimethylarginines levels were different in PAH patients compared to LVHF patients and healthy controls. PAH-specific treatment influenced L-arginine and dimethylarginines. Our data suggest that L-arginine might be useful for differentiating PAH from LVHF, and L-arginine/ADMA ratios were related to the severity of PAH and might be useful for follow-up evaluations of PAH patients.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2016. p. 73
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1747
Keywords
vardenafil, pulmonary hypertension, pharmacokinetics, haemodynamics, right heart catheterization, adenosine, dimethylarginines, phosphodiesterase type 5 inhibitors, endothelin receptor antagonists
National Category
Pharmacology and Toxicology Cardiac and Cardiovascular Systems
Research subject
Clinical Pharmacology
Identifiers
urn:nbn:se:umu:diva-113903 (URN)978-91-7601-376-2 (ISBN)
Public defence
2016-01-22, Hörsal B, tandläkarhögskolan våning 9, Norrlands universitetssjukhus, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2016-01-08 Created: 2016-01-05 Last updated: 2018-06-07Bibliographically approved
Sandqvist, A., Henrohn, D., Egeröd, H., Hedeland, M., Wernroth, L., Bondesson, U., . . . Wikström, G. (2015). Acute vasodilator response to vardenafil and clinical outcome in patients with pulmonary hypertension. European Journal of Clinical Pharmacology, 71(10), 1165-1173
Open this publication in new window or tab >>Acute vasodilator response to vardenafil and clinical outcome in patients with pulmonary hypertension
Show others...
2015 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 71, no 10, p. 1165-1173Article in journal (Refereed) Published
Abstract [en]

PURPOSE: 

Acute vasodilator testing is recommended in patients with pulmonary arterial hypertension to identify individuals who may benefit from long-term treatment with oral calcium channel blockers. The aim of this study was to investigate the use of vardenafil in acute vasoreactivity testing compared to adenosine.

METHODS: 

A total of 20 patients eligible for right heart catheterisation were enrolled. Acute vasoreactivity testing was carried out with intravenous (iv) adenosine (n = 18) followed by oral vardenafil (n = 20). Haemodynamic responses were recorded at baseline and after 60 min (vardenafil). Responders were defined according to consensus guideline criteria.

RESULTS: 

Both vardenafil and adenosine significantly decreased mean pulmonary arterial pressure (mPAP, p < 0.001 and p = 0.026, respectively) and pulmonary vascular resistance (p < 0.001 and p > 0.001, respectively), and significantly increased cardiac output (p = 0.001 and p = 0.005, respectively). Vardenafil reduced mPAP more than adenosine (p = 0.044), while adenosine resulted in higher responses of cardiac index (p = 0.009) and pulmonary arterial oxygen saturation (p = 0.042). Acute adverse reactions were common with adenosine, while no side effects were observed after a single oral dose vardenafil. Vardenafil identified five responders (out of 20), while adenosine identified three responders (out of 18). During a 7-year follow-up, vardenafil responders had significantly lower NT-proBNP levels compared to non-responders.

CONCLUSIONS: 

Vardenafil may be safely used for acute vasoreactivity testing in patients with PH. A single oral dose of vardenafil is better tolerated than iv adenosine and may identify additional responders who could benefit from long-term vasodilator treatment.

Keywords
denosine, Vardenafil, Acute vasodilator test, Haemodynamics, Pulmonary hypertension, Right heart catheterisation
National Category
Cardiac and Cardiovascular Systems Pharmacology and Toxicology
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-108234 (URN)10.1007/s00228-015-1914-z (DOI)000360996300002 ()26242227 (PubMedID)
Available from: 2015-09-07 Created: 2015-09-07 Last updated: 2018-06-07Bibliographically approved
Henrohn, D., Sandqvist, A., Egeröd, H., Hedeland, M., Wernroth, L., Bondesson, U. & Wikström, G. (2015). Changes in plasma levels of asymmetric dimethylarginine, symmetric dimethylarginine, and arginine after a single dose of vardenafil in patients with pulmonary hypertension. Vascular pharmacology, 73, 71-77
Open this publication in new window or tab >>Changes in plasma levels of asymmetric dimethylarginine, symmetric dimethylarginine, and arginine after a single dose of vardenafil in patients with pulmonary hypertension
Show others...
2015 (English)In: Vascular pharmacology, ISSN 1537-1891, E-ISSN 1879-3649, Vol. 73, p. 71-77Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: We investigated whether vardenafil, a phosphodiesterase-5 inhibitor, alters plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and arginine.

PATIENTS AND METHODS: ADMA, SDMA, and arginine were measured (0-540min) in 12 patients with pulmonary hypertension after a single oral dose of vardenafil. Invasive hemodynamic data were collected at baseline and after 60min.

RESULTS: A reduction in ADMA was observed at 30 and 45min with a median change of -11.1% (P=0.021) and -12.5% (P=0.002). SDMA decreased with a median -5.3% change (P=0.032) at 45min. An increase in arginine, median 40.3% (P=0.002), 45.0% (P=0.010), and 77.1% (P=0.008) was observed at 120, 300, and 540min respectively. An increase in the arginine/ADMA ratio, median 11.7% (P=0.012), 32.5% (P=0.003), 26.5% (P=0.021), 33% (P=0.007), 48.5% (P=0.007), and 63.1% (P=0.008) was observed at 15, 45, 60, 120, 300, and 540min respectively. There was a positive correlation between vardenafil exposure and the percent change in the arginine/ADMA ratio from baseline to 540min (r=0.80; P=0.01). A correlation between baseline mean right atrial pressure (mRAP) and baseline ADMA (r=0.65; P=0.023), and baseline SDMA (r=0.61; P=0.035) was observed. A correlation between the baseline arginine/ADMA ratio and baseline cardiac output (CO) (r=0.59; P=0.045) and baseline cardiac index (CI) (r=0.61; P=0.036) was observed. Baseline arginine/ADMA ratio correlated with baseline mRAP (r=-0.79; P=0.002). A correlation between change (0-60min) in CI and change in arginine (r=0.77; P=0.003) as well as change in the arginine/ADMA ratio (r=0.61; P=0.037) was observed.

CONCLUSIONS: Vardenafil induced changes in ADMA, SDMA, arginine, and the arginine/ADMA ratio in patients with PH. An increase in arginine and the arginine/ADMA ratio was associated with improvement in CI.

Keywords
Pulmonary hypertension, Vardenafil, Hemodynamics, Dimethylarginines, Arginine
National Category
Pharmacology and Toxicology
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-106681 (URN)10.1016/j.vph.2015.04.010 (DOI)000362056600011 ()25934511 (PubMedID)
Available from: 2015-09-06 Created: 2015-08-01 Last updated: 2018-06-07Bibliographically approved
Sandqvist, A. & Ottander, P. (2015). Laktos i läkemedel normalt inget problem för laktosintoleranta. Läkartidningen, 112(27-28), 1234-1234
Open this publication in new window or tab >>Laktos i läkemedel normalt inget problem för laktosintoleranta
2015 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 27-28, p. 1234-1234Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Läkartidningen förlag AB, 2015
National Category
Pharmacology and Toxicology
Research subject
Clinical Pharmacology
Identifiers
urn:nbn:se:umu:diva-108238 (URN)
Available from: 2015-09-07 Created: 2015-09-07 Last updated: 2018-06-07Bibliographically approved
Sandqvist, A., Henrohn, D., Schneede, J., Hedeland, M., Egerod, H. C., Bondesson, U. G. & Wikstrom, B. G. (2013). High inter-individual variability of vardenafil pharmacokinetics in patients with pulmonary hypertension. European Journal of Clinical Pharmacology, 69(2), 197-207
Open this publication in new window or tab >>High inter-individual variability of vardenafil pharmacokinetics in patients with pulmonary hypertension
Show others...
2013 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 69, no 2, p. 197-207Article in journal (Refereed) Published
Abstract [en]

To evaluate the pharmacokinetic parameters of a single oral dose of vardenafil in patients with pulmonary hypertension (PH). Sixteen patients with PH received vardenafil in single oral doses (20, 10 or 5 mg), and repeated blood sampling for up to 9 h was performed. Vardenafil plasma concentration was determined using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using model-independent analysis. The plasma vardenafil concentration increased rapidly and exhibited a median time to maximum plasma concentration (t(max)) of 1 h and a mean elimination half-life (t(1/2)) of 3.4 h. The geometric mean and standard deviation of (1) the peak plasma concentration (C-max) was 21.4 +/- 1.7 mu g/L, (2) the normalized C-max (C-max,C- norm) 79.1 +/- 1.6 g/L, (3) the area under the time-concentration curve (AUC) 71.5 +/- 1.6 mu g center dot h/L and (4) the normalized AUC (AUC(norm)) 261.6 A +/- 1.7 g center dot h/L. Patients co-medicated with bosentan reached t(max) later and had a 90% reduction of C-max, C-max,C- norm, AUC and AUC(norm). The pharmacokinetic profile of vardenafil overall revealed considerable inter-individual variability in patients with PH. Co-medication with bosentan resulted in a pharmacokinetic drug interaction, leading to significantly decreased plasma concentrations of vardenafil. Therapeutic drug monitoring for individual dose optimization may be warranted.

Keywords
Vardenafil, Population pharmacokinetics, Pulmonary hypertension, Right heart catheterization, Phosphodiesterase type 5 inhibitors
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-66639 (URN)10.1007/s00228-012-1323-5 (DOI)000313791600008 ()
Available from: 2013-03-06 Created: 2013-02-26 Last updated: 2018-06-08Bibliographically approved
Henrohn, D., Sandqvist, A., Hedeland, M., Egerod, H., Bondesson, U. & Wikstrom, G. (2012). Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension. British Journal of Clinical Pharmacology, 74(6), 990-998
Open this publication in new window or tab >>Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension
Show others...
2012 (English)In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 74, no 6, p. 990-998Article in journal (Refereed) Published
Abstract [en]

AIMS To evaluate the acute haemodynamic effects of a single oral dose of vardenafil and to study the drug concentration in relation to haemodynamic effects in patients with pulmonary hypertension (PH). METHODS Sixteen patients with PH (aged 29-85\ years), received one single oral dose of vardenafil (5, 10 or 20 mg). The haemodynamic effect was assessed over a 60 min period. Vardenafil plasma concentrations were measured after 15, 30, 45 and 60 min using liquid chromatography-tandem mass spectrometry. RESULTS At 60 min a reduction in mPAP with a median % decrease of -20.3% (range -48.3 to 3.0; P < 0.001) and an increase in cardiac output and the cardiac index with a median % change of 10.6% (range -25.0 to 88.1; P = 0.015) and 12.1% (range -24.0 to 94.4; P = 0.01) respectively was observed. The pulmonary vascular resistance (PVR) was reduced with a median % decrease of -28.9% (range -61.5 to -5.9; P < 0.001), and pulmonary selectivity was reflected by a median percent reduction of -16.9% (range -49.0 to 16.5; P = 0.002; n = 14) in the PVR/ systemic vascular resistance ratio. There was a correlation between the plasma concentrations of vardenafil and change in mPAP (r = -0.579, P = 0.019) and between vardenafil concentrations and change in PVR (r = -0.662, P = 0.005). CONCLUSIONS Vardenafil causes rapid changes in cardiopulmonary haemodynamics and there is a correlation between plasma vardenafil drug concentration and the acute changes in mPAP as well as PVR in patients with PH.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2012
Keywords
haemodynamics, pharmacokinetics, phosphodiesterase inhibitor, pulmonary hypertension, right heart catheterization, vardenafil
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-62780 (URN)10.1111/j.1365-2125.2012.04303.x (DOI)000311108800011 ()
Available from: 2013-01-02 Created: 2012-12-18 Last updated: 2018-06-08Bibliographically approved
Holmgren, H. M., Sandqvist, A. & Schneede, J. (2011). Preoperativ utsättning av läkemedel som påverkar hemostasen: evidensbaserad rekommendation. Läkartidningen, 108(37), 1754-1759
Open this publication in new window or tab >>Preoperativ utsättning av läkemedel som påverkar hemostasen: evidensbaserad rekommendation
2011 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 37, p. 1754-1759Article in journal (Refereed) Published
Abstract [sv]

Artikeln presenterar en evidensbaserad rekommendation för hantering av läkemedel som påverkar hemostasen inför planerad operation. Till grund för rekommendationen ligger en litteraturstudie av utsättningstider, förutom ­tidigare kända rekommendationer.

De läkemedel som har utretts ingår i ATC-koderna B01A (antikoagulantia) och M01A (icke-steroida antiinflammatoriska medel, NSAID).

Beslut om utsättning av läkemedel som påverkar hemostasen är alltid en avvägning mellan ökad blödningsrisk i samband med operation och trombosrisk vid seponering.

Individuell bedömning av blödningsrisk och trombosrisk är nödvändig. Hänsyn måste tas till patientfaktorer, den primära indikationen för antitrombotisk behandling, vilka antikoagulantia som används samt typ av operation och anestesimetod.

Place, publisher, year, edition, pages
Stockholm: Sveriges läkarförbund, 2011
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:umu:diva-56760 (URN)22046660 (PubMedID)
Available from: 2012-06-26 Created: 2012-06-26 Last updated: 2018-06-08Bibliographically approved
Organisations

Search in DiVA

Show all publications