Publications by authors named "Torbjörn Karlsson"

50 Publications

Increased Plasma GDF15 Is Associated with Altered Levels of Soluble VEGF Receptors 1 and 2 in Symptomatic Multiple Myeloma.

Acta Haematol 2021 Nov 24:1-8. Epub 2021 Nov 24.

Department of Medical Science, Uppsala University, Uppsala, Sweden.

Introduction: In multiple myeloma, there is an increase in bone marrow microvascular density and enhanced renal lymphangiogenesis. Increased levels of the proangiogenic protein growth differentiation factor-15 (GDF15) have previously been reported to be associated with poor prognosis in myeloma. A possible association between GDF15 and the soluble forms of vascular endothelial growth factor receptors (sVEGFR) 1 and 2 has not yet been investigated, and a role for these receptors in pathological angiogenesis in myeloma is still to be defined.

Methods: Plasma levels of GDF15 and sVEGFR1 and 2 were determined by ELISA in patients with smouldering multiple myeloma (sMM), patients with symptomatic multiple myeloma (abbreviated as MM), and healthy controls. The levels were compared between the three groups, and correlation coefficients were calculated, as were Kaplan-Meier curves for GDF15 and sVEGFR1 and sVEGFR2.

Results: Levels of GDF15 were significantly higher in MM than in both patients with sMM and controls. A gradual decrease in mean sVEGFR1 concentration was observed, with MM > sMM > controls. Mean sVEGFR2 was lower in patients with MM than in controls. There was a positive correlation between GDF15 and sVEGFR1, and GDF15 correlated negatively with sVEGFR2. High GDF15 (>3 ng/mL) was associated with poor prognosis.

Conclusion: In multiple myeloma, increased expression of GDF15 correlates positively with sVEGFR1 and negatively with sVEGFR2. It is possible that the altered levels of sVEGFR1 and 2 contribute to the increased angio- and lymphangiogenesis observed in myeloma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000519888DOI Listing
November 2021

Increased levels of the cardiovascular disease risk biomarkers GDF15 and myostatin in patients with chronic lymphocytic leukemia.

Growth Factors 2020 Jun-Jul;38(3-4):189-196

Department of Medical Sciences, Division of Hematology, University Hospital, Uppsala, Sweden.

Individuals suffering from cancer, including hematological malignancies, are at increased risk of cardiovascular disease (CVD). Elevated levels of several biomarkers in blood are associated with an increased risk of CVD. The aim of this study was to investigate whether a subset of such CVD risk biomarkers was elevated in patients with untreated chronic lymphocytic leukemia (CLL). Blood plasma and serum from 139 CLL patients and 71 healthy age-matched controls were analyzed for 11 proposed CVD risk biomarkers. The CLL cohort displayed a more heterogeneous pattern of biomarker expression compared to controls. The majority, eight out of 11, analyzed CVD risk biomarkers differed significantly in concentrations between CLL patients and controls. Increased levels of the biomarkers GDF15 and myostatin have not previously been reported in CLL. Further prospective studies are warranted to investigate whether these biomarkers predict future cardiovascular events in patients with CLL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08977194.2021.1932870DOI Listing
June 2021

Falsely Elevated Thyroid-Stimulating Hormone Results due to Interference by M-Component of IgG-Lambda Type.

Case Rep Oncol 2020 May-Aug;13(2):680-682. Epub 2020 Jun 16.

Section of Haematology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Heterophilic antibodies but also M-components can interfere with laboratory tests causing erroneous results. We report the case of a 75-year-old man with myeloma and a monoclonal immunoglobulin component (M-component) that caused elevated thyroid-stimulating hormone (TSH) results. The M-component was of the IgG-lambda type. Thyroid markers were analyzed repeatedly, and there was a clear association between IgG concentrations and TSH values ( = 0.724). The highest TSH value was 75 mIU/L. Polyethylene glycol (PEG) precipitation of intact immunoglobulins was used to investigate if there was an antibody-related interference problem. The PEG treatment normalized the TSH value, showing that the cause of the elevated TSH result was due to interference caused by the M-component. In conclusion, it is important to remember that both heterophilic antibodies and M-components may cause erroneous results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000507754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383168PMC
June 2020

Daily systemic energy expenditure in the acute phase of aneurysmal subarachnoid hemorrhage.

Ups J Med Sci 2019 Nov;124(4):254-259

Department of Surgical Sciences, Section of Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.

Patients with subarachnoid hemorrhage often have impaired consciousness and cannot regulate nutritional intakes themselves. Previous studies have demonstrated elevated energy expenditure in the acute phase, but it is not known whether the energy demand is constant during the first week after onset of the disease. In this study, we performed daily measurements of energy expenditure with indirect calorimetry during the first 7 days after aneurysmal subarachnoid hemorrhage in mechanically ventilated patients. Metabolic measurements were performed daily with indirect calorimetry in 26 patients with aneurysmal subarachnoid hemorrhage. All patients were intubated and mechanically ventilated. The measured value was compared to the predicted values from the Harris-Benedict equation and the Penn State University 1998 equation. Urinary nitrogen excretion was measured daily. There was a significant increase in energy expenditure during days 2-3 compared to days 5-6. The Harris-Benedict equation underestimated metabolic demand. The Penn State 1998 equation was closer to the measured values, but still underestimated caloric need. Urinary nitrogen excretion increased throughout the first week from initially low values. There is a dynamic course in energy expenditure in patients with aneurysmal subarachnoid hemorrhage, with increasing metabolic demand during the first week of the disease. Indirect calorimetry could be used more often to help provide an adequate amount of energy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03009734.2019.1659888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968686PMC
November 2019

Mutations in the ENG, ACVRL1, and SMAD4 genes and clinical manifestations of hereditary haemorrhagic telangiectasia: experience from the Center for Osler's Disease, Uppsala University Hospital.

Ups J Med Sci 2018 Sep 25;123(3):153-157. Epub 2018 Sep 25.

a Department of Haematology , Uppsala University Hospital , Uppsala , Sweden.

Aim: The aim of this retrospective single-centre study was to evaluate whether mutations in the ENG, ACVRL1, and SMAD4 genes were associated with different phenotypes in hereditary haemorrhagic telangiectasia (HHT).

Methods: The case records of 21 HHT patients with verified mutations in ENG, ACVRL1, or SMAD4 genes were reviewed. The numbers of HHT diagnostic criteria fulfilled for the three genotypes were compared, as was the prevalence of complications such as iron deficiency anaemia, gastrointestinal haemorrhage, stroke, and cerebral abscess.

Results: Our results indicate that mutations in the ENG (HHT1), ACVRL1 (HHT2), and SMAD4 genes result in different HHT phenotypes. Epistaxis debuts earlier and may be more severe in HHT1 than in HHT2. The prevalence of pulmonary arteriovenous malformations (AVM) is higher in HHT type 1, whereas hepatic AVMs are more common in HHT2. One patient with mutations in both ENG and ACVRL1 genes was identified, as were two SMAD4-mutated patients suffering from the overlapping juvenile polyposis-HHT syndrome. Nearly one in five patients in our HHT population has been diagnosed with stroke or cerebral abscess, indicating a high prevalence of cerebral complications.

Conclusion: Our results showing that ENG and ACVRL1 gene mutations result in different HHT phenotypes confirm the results from other HHT centres worldwide. Cerebral complications of HHT are common, underscoring the importance of regular screening for pulmonary AVMs and early intervention against such AVMs. We have identified an HHT patient with simultaneous mutations in the ENG and ACVRL1 genes. Surprisingly, this patient has had a mild course of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03009734.2018.1483452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198721PMC
September 2018

Evaluation of a competitive hepcidin ELISA assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients.

J Inflamm (Lond) 2017 18;14:21. Epub 2017 Sep 18.

Department of Haematology, Uppsala University Hospital, 751 85 Uppsala, Sweden.

In this study, a competitive hepcidin ELISA assay was evaluated for its ability to differentiate between iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients, using the absence of stainable bone marrow iron as the diagnostic criterion for iron deficiency. In addition, correlation coefficients for hepcidin versus C-reactive protein, ferritin and interleukin-6 were determined. The optimal cut-off for hepcidin was 21 μg/L, corresponding to sensitivity and specificity of 100% and 67%, respectively, for iron deficiency. For ferritin, a sensitivity and specificity of 91% and 83%, respectively, correspond to an optimal cut-off of 87 μg/L. Receiver operating characteristics curve analysis revealed that ELISA analysis of hepcidin is not superior to ferritin in the diagnosis of iron deficiency in elderly anaemic patients with concurrent inflammation. Hepcidin shows a strong positive correlation with ferritin, and also correlates positively with C-reactive protein in this patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12950-017-0166-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604302PMC
September 2017

Effect of Intravenous Iron Supplementation on Iron Stores in Non-Anemic Iron-Deficient Patients with Hereditary Hemorrhagic Telangiectasia.

Hematol Rep 2016 Mar 21;8(1):6348. Epub 2016 Mar 21.

Department of Hematology and Center for Osler's Disease, Uppsala University Hospital , Uppsala, Sweden.

In hereditary hemorrhagic telangiectasia (HHT), frequent episodes of nasal and gastrointestinal bleeding commonly lead to iron-deficiency with or without anemia. In the retrospective study presented here we assessed the iron stores, as determined by analysis of plasma ferritin, during oral and intravenous iron supplementation, respectively, in a population of iron-deficient non-anemic HHT patients who were inadequately iron-repleted by oral supplementation. A switch from oral to intravenous iron supplementation was associated with a significant increase in ferritin in this patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/hr.2016.6348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815949PMC
March 2016

The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage.

PLoS One 2016 23;11(3):e0151457. Epub 2016 Mar 23.

Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden.

Introduction: In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH), a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems.

Methods: A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, catecholamines and chromogranin-A were performed.

Results: Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased.

Conclusions: The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151457PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805209PMC
August 2016

Secondary haemophagocytic lymphohistiocytosis: Experience from the Uppsala University Hospital.

Ups J Med Sci 2015 25;120(4):257-62. Epub 2015 Jul 25.

a Department of Haematology, Uppsala University Hospital , Uppsala, Sweden.

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple-organ failure. HLH in adults is often secondary to autoimmune diseases, cancer, or infections in contrast to familial HLH. Treatment of secondary HLH is directed against the triggering disease in addition to immunosuppressive therapy, the latter commonly according to the HLH-2004 protocol.

Methods: We conducted a retrospective study to identify triggering diseases, disease-specific and immunosuppressive therapy administered, and prognosis in adult patients with secondary HLH. Patient data were collected from October 2010 to January 2015.

Results: Ten adult patients with secondary HLH were identified. Seven were men, and the median age at diagnosis was 62 years. Five cases were triggered by malignant disease and five by infection. The median patient fulfilled five of the eight HLH-2004 diagnostic criteria. All patients fulfilled the criteria fever, cytopenia, and ferritin >500 µg/L. Median time from hospital admission to HLH diagnosis was 20 days. Four patients received immunosuppressive therapy according to the HLH-2004 protocol. The prognosis was dismal, especially for the patients with malignancy-associated HLH, of whom all died.

Conclusion: HLH should be suspected in patients who present with fever, cytopenia, and ferritin >500 µg/L. Secondary HLH has a dismal prognosis. None of the patients with HLH triggered by malignancy survived. Achieving remission of the triggering disease seems to be important for a favourable outcome as, in all surviving patients, the haemophagocytic syndrome resolved after remission of the underlying infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/03009734.2015.1064500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816886PMC
August 2016

Progress and Milestones in Scientific Communication--a 150 years perspective.

Ups J Med Sci 2015 May 14;120(2):63-4. Epub 2015 Apr 14.

Chairman of the Upsala Medical Society , Uppsala , Sweden.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/03009734.2015.1022669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463477PMC
May 2015

Mass spectrometry evaluation of the hepcidin-25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients.

Eur J Haematol 2015 Nov 10;95(5):467-71. Epub 2015 Feb 10.

Department of Haematology, Uppsala University Hospital, Uppsala, Sweden.

In this study, mass spectrometry was used to evaluate the hepcidin-25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients using the absence of stainable bone marrow iron as the gold standard criterion for iron deficiency (ID). In addition, correlation coefficients for hepcidin-25 vs. haematimetric and biochemical iron parameters, and C-reactive protein (CRP) were determined. The optimal cut-off for hepcidin-25 was 31.5 ng/mL corresponding to a sensitivity and specificity of 82% and 95%, respectively, for ID. For ferritin, a sensitivity and specificity of 70% and 100%, respectively, correspond to an optimal cut-off of 41.5 μg/L. Receiver operating characteristics curve analysis revealed that mass spectrometry analysis of hepcidin-25 does not appear to be superior to ferritin in the diagnosis of ID in elderly anaemic patients with concurrent inflammation. Hepcidin-25 shows a strong positive correlation with ferritin, and also correlates positively with CRP, in this patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejh.12518DOI Listing
November 2015

Intravenous iron alone resolves anemia in patients with functional iron deficiency and lymphoid malignancies undergoing chemotherapy.

Med Oncol 2014 Dec 6;31(12):302. Epub 2014 Nov 6.

Department of Internal Medicine, Sundsvall Hospital, 851 86, Sundsvall, Sweden,

This randomized trial evaluated ferric carboxymaltose without erythropoiesis-stimulating agents (ESA) for correction of anemia in cancer patients with functional iron deficiency. Patients on treatment for indolent lymphoid malignancies, who had anemia [hemoglobin (Hb) 8.5-10.5 g/dL] and functional iron deficiency [transferrin saturation (TSAT) ≤ 20%, ferritin >30 ng/mL (women) or >40 ng/mL (men)], were randomized to ferric carboxymaltose (1,000 mg iron) or control. Primary end point was the mean change in Hb from baseline to weeks 4, 6 and 8 without transfusions or ESA. Difficulties with patient recruitment led to premature termination of the study. Seventeen patients (8 ferric carboxymaltose and 9 control) were included in the analysis. In the ferric carboxymaltose arm, mean Hb increase was significantly higher versus control at week 8 (p = 0.021). All ferric carboxymaltose-treated patients achieved an Hb increase >1 g/dL (control 6/9; p = 0.087), and mean TSAT was >20% from week 2 onwards. No treatment-related adverse events were reported. In conclusion, ferric carboxymaltose without ESA effectively increased Hb and iron status in this small patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12032-014-0302-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221625PMC
December 2014

Combination treatment with an erythropoiesis-stimulating agent and intravenous iron alleviates anaemia in patients with hereditary haemorrhagic telangiectasia.

Ups J Med Sci 2014 Nov 4;119(4):350-3. Epub 2014 Sep 4.

Department of Haematology, Uppsala University Hospital , Uppsala , Sweden.

Background: Patients with hereditary haemorrhagic telangiectasia (HHT) suffer from recurrent epistaxis and bleeding from gastrointestinal telangiectasias that occur despite otherwise normal haemostasis and result in iron deficiency anaemia with increasing severity. In advanced disease, anaemia may be severe, be irresponsive to iron supplementation, and may lead to red blood cell transfusion dependency.

Methods: We conducted a retrospective study at our Centre for Osler's Disease to evaluate the effectiveness of adding an erythropoiesis-stimulating agent (ESA) to intravenous iron supplementation in the management of anaemic HHT patients. Blood values and treatment parameters were collected for nine months before combination therapy (iron supplementation only) and 12 months during combination therapy (iron supplementation plus ESA).

Results: Four patients received intravenous iron and an ESA with mean weekly doses of 126 mg and 17,300 units (U), respectively. Mean haemoglobin improved significantly during combination therapy, from 106 g/L to 119 g/L (p < 0.001).

Conclusion: Anaemia can be alleviated in patients with HHT who are irresponsive to intravenous iron supplementation, by addition of an ESA. The proposed mechanism behind the iron irresponsiveness is that the anaemia is caused by a combination of recurrent haemorrhage and anaemia of chronic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/03009734.2014.955619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248076PMC
November 2014

Metabolic pattern of the acute phase of subarachnoid hemorrhage in a novel porcine model: studies with cerebral microdialysis with high temporal resolution.

PLoS One 2014 18;9(6):e99904. Epub 2014 Jun 18.

Department of Neuroscience, section of Neurosurgery, Uppsala University, Uppsala, Sweden.

Background: Aneurysmal subarachnoid hemorrhage (SAH) may produce cerebral ischemia and systemic responses including stress. To study immediate cerebral and systemic changes in response to aneurysm rupture, animal models are needed.

Objective: To study early cerebral energy changes in an animal model.

Methods: Experimental SAH was induced in 11 pigs by autologous blood injection to the anterior skull base, with simultaneous control of intracranial and cerebral perfusion pressures. Intracerebral microdialysis was used to monitor concentrations of glucose, pyruvate and lactate.

Results: In nine of the pigs, a pattern of transient ischemia was produced, with a dramatic reduction of cerebral perfusion pressure soon after blood injection, associated with a quick glucose and pyruvate decrease. This was followed by a lactate increase and a delayed pyruvate increase, producing a marked but short elevation of the lactate/pyruvate ratio. Glucose, pyruvate, lactate and lactate/pyruvate ratio thereafter returned toward baseline. The two remaining pigs had a more severe metabolic reaction with glucose and pyruvate rapidly decreasing to undetectable levels while lactate increased and remained elevated, suggesting persisting ischemia.

Conclusion: The animal model simulates the conditions of SAH not only by deposition of blood in the basal cisterns, but also creating the transient global ischemic impact of aneurysmal SAH. The metabolic cerebral changes suggest immediate transient substrate failure followed by hypermetabolism of glucose upon reperfusion. The model has features that resemble spontaneous bleeding, and is suitable for future research of the early cerebral and systemic responses to SAH that are difficult to study in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099904PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062436PMC
July 2015

The gallium(III)-salicylidene acylhydrazide complex shows synergistic anti-biofilm effect and inhibits toxin production by Pseudomonas aeruginosa.

J Inorg Biochem 2014 Sep 23;138:1-8. Epub 2014 Apr 23.

Department of Chemistry, Umeå University, 90187 Umeå, Sweden. Electronic address:

Bacterial biofilms cause a range of problems in many areas and especially in health care. Biofilms are difficult to eradicate with traditional antibiotics and consequently there is a need for alternative ways to prevent and/or remove bacterial biofilms. Furthermore, the emergence of antibiotic resistance in bacteria creates a challenge to find new types of antibiotics with a lower evolutionary pressure for resistance development. One route to develop such drugs is to target the so called virulence factors, i.e. bacterial systems used when bacteria infect a host cell. This study investigates synergy effects between Ga(III) ions, previously reported to suppress biofilm formation and growth in bacteria, and salicylidene acylhydrazides (hydrazones) that have been proposed as antivirulence drugs targeting the type three secretion system used by several Gram-negative pathogens, including Pseudomonas aerugionosa, during bacterial infection of host cells. A library of hydrazones was screened for: Fe(III) binding, enhanced anti-biofilm effect with Ga(III) on P. aeruginosa, and low cytotoxicity to mammalian cells. The metal coordination for the most promising ligand, 2-Oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (ME0163) with Ga(III) was investigated using extended X-ray absorption fine structure spectroscopy as well as density functional theory. The results showed that Ga(III) chelates the hydrazone with 5- and 6-membered chelating rings, and that the Ga(III)-ME0163 complex enhanced the antibiofilm effect of Ga(III) while suppressing the type three secretion system in P. aeruginosa. The latter effect was not observed for the hydrazone alone and was similar for Ga(III)-citrate and Ga(III)-ME0163 complexes, indicating that the inhibition of virulence was caused by Ga(III).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinorgbio.2014.04.009DOI Listing
September 2014

Predictors of increased cumulative serum levels of the N-terminal prohormone of brain natriuretic peptide 4 days after acute spontaneous subarachnoid hemorrhage.

J Neurosurg 2014 Mar 4;120(3):599-604. Epub 2013 Oct 4.

Department of Neuroscience, Section of Neurosurgery, and.

Object: The rupture of an intracranial aneurysm is followed by increased intracranial pressure and decreased cerebral blood flow. A major systemic stress reaction follows, presumably to restore cerebral blood flow. However, this reaction can also cause adverse effects, including myocardial abnormalities, which are common and can be serious, and increased levels of natriuretic peptides, especially brain natriuretic peptide (BNP). The association of BNP with fluid and salt balance, vasospasm, brain ischemia, and cardiac injury has been studied but almost exclusively regarding events after admission. Brain natriuretic peptide has also been measured at various time points and analyzed in different ways statistically. The authors approached BNP measurement in a new way; they used the calculated area under the curve (AUC) for the first 4 days to quantitatively measure the BNP load during the first critical part of the disease state. Their rationale was a suspicion that early BNP load is a marker of the severity of the ictus and will influence the subsequent course of the disease by disturbing the fluid and salt balance.

Methods: The study included 156 patients with acute spontaneous subarachnoid hemorrhage (SAH). Mean patient age was 59.8 ± 11.2 years, and 105 (67%) of the patients were female. An aneurysm was found in 138 patients. A total of 82 aneurysms were treated by endovascular coiling, 50 were treated by surgery, and 6 were untreated. At the time of admission, serum samples were collected for troponin-I analysis and for the N-terminal prohormone of BNP (NT-proBNP); daily thereafter, samples were collected for the NT-proBNP analysis. The cumulative BNP load was calculated as the AUC for NT-proBNP during the first 4 days. The following variables were studied in terms of their influence on the AUC for NT-proBNP: sex, age, World Federation of Neurosurgical Societies grade of SAH, Fisher grade, angiographic result, treatment of aneurysm, clinical neurological deterioration, verified infections, vasospasm treatment, and 6-month outcome.

Results: The AUC for NT-proBNP was larger when variables indicated a more severe SAH. These variables were higher Fisher and World Federation of Neurosurgical Societies grades, high levels of troponin-I at admission, an aneurysm, neurological deficits, and infections. The AUC for NT-proBNP was also larger among women, older patients, and patients with poor outcomes. Linear regression showed that the best predicting model for large AUC for NT-proBNP was the combination of the following: female sex, high levels of troponin-I, an aneurysm, neurological deficits, and advanced age.

Conclusions: The cumulative BNP load during the first days after SAH can be predicted by variables describing the severity of the disease already known at the time of admission. This information can be used to identify patients at risk for an adverse course of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2013.8.JNS13625DOI Listing
March 2014

An experimental protocol for structural characterization of Fe in dilute natural waters.

Environ Sci Technol 2013 Aug 19;47(15):8557-64. Epub 2013 Jul 19.

Department of Chemistry, Umeå University , SE-901 87 Umeå, Sweden.

The properties of iron (Fe) complexes and compounds in the environment influence several central processes, e.g., iron uptake, adsorption/desorption of contaminants and nutrients, and redox transformations, as well as the fate of of natural organic matter (NOM). It is thus important to characterize Fe species in environmental samples. Synchrotron-based extended X-ray absorption fine structure (EXAFS) spectroscopy has been used in several studies on soils and sediments, but literature is scarce on investigations of natural waters because of low Fe concentrations. In this study we have described a gentle and noninvasive preconcentration method, based on electrostatic adsorption onto ion-exchange resins, suitable for EXAFS analysis of Fe species in dilute stream water samples. The EXAFS results of metal-organic model complexes showed that no significant local structural distortions were induced by the method. We also demonstrated the feasibility for an 8 μM Fe stream water sample. The Fe heterogeneity in this stream water was investigated via a gradient series at 28%, 42%, 77%, 84%, and 100% adsorption of total iron. The EXAFS results showed that Fe(III) in this stream water was divided into Fe(III)-NOM complexes and Fe(III) (oxyhydr)oxides associated with NOM, and that each class consisted of several subspecies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/es304630aDOI Listing
August 2013

[Do a total remake].

Lakartidningen 2013 Apr 10-16;110(15):775

View Article and Find Full Text PDF

Download full-text PDF

Source
July 2013

[Swedish laws applies here too].

Lakartidningen 2013 Mar 26-Apr 9;110(13-14):698

View Article and Find Full Text PDF

Download full-text PDF

Source
July 2013

Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study.

Eur J Haematol 2012 Jun 30;88(6):485-96. Epub 2012 Mar 30.

Department of Medicine, Lidköping Hospital, Lidköping, Sweden.

Objectives: Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives.

Methods: Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms.

Results: After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group.

Conclusions: Thalidomide (50-100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0609.2012.01775.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492844PMC
June 2012

Cortisol and adrenocorticotropic hormone dynamics in the acute phase of subarachnoid haemorrhage.

Br J Neurosurg 2011 Dec;25(6):684-92

Department of Neuroscience, Section of Neurosurgery, Uppsala University Hospital, Sweden.

Objective: An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimising care in the acute phase of SAH.

Patients: Fifty-five patients with spontaneous SAH were evaluated regarding morning concentrations of serum (S)-cortisol and P-adrenocorticotropic hormone (ACTH) 7 days after the bleeding. In a subgroup of 20 patients, the diurnal changes of S-cortisol and P-ACTH were studied and urine (U)-cortisol was measured. The relationships of hormone concentrations to clinical and radiological parameters and to outcome were assessed.

Results: S-cortisol and P-ACTH were elevated the day of SAH. S-cortisol concentrations below reference range were uncommon. Early global cerebral oedema was associated with higher S-cortisol concentrations at admission and a worse World Federation of Neurological Surgeons (WFNS) and Reaction Level Scale 85 grade. Global cerebral oedema was shown to be a predictor of S-cortisol at admittance. Patients in better WFNS grade displayed higher U-cortisol. All patients showed diurnal variations of S-cortisol and P-ACTH. A reversed diurnal variation of S-cortisol was more frequently found in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-cortisol peaks occurred especially in periods of secondary brain ischaemia.

Conclusion: There was an HPA response acutely after SAH with an increase in P-ACTH and S-cortisol. Higher U-cortisol in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-cortisol at admission and was a predictor of S-cortisol concentrations. Global cerebral oedema may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischaemia, indicating a possible connection between brain ischaemia and ACTH suppression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/02688697.2011.584638DOI Listing
December 2011

Effects of iron supplementation on erythropoietic response in patients with cancer-associated anemia treated by means of erythropoietic stimulating agents.

ISRN Hematol 2011 13;2011:108397. Epub 2011 Oct 13.

Department of Hematology, Uppsala University Hospital, 751 85 Uppsala, Sweden.

During the past decade, intravenous iron supplementation to ESA (erythropoiesis-stimulating agent) therapy has emerged as an option to augment hemoglobin response in anemic cancer patients. In this paper, the results of seven published randomized clinical trials assessing the role of iron supplementation to ESA therapy in the hematology/oncology setting will be discussed. The pathogenetic mechanisms behind functional iron deficiency, a major reason for ESA hyporesponsiveness in cancer, will also be described.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5402/2011/108397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196863PMC
November 2011

Comparative evaluation of the reticulocyte hemoglobin content assay when screening for iron deficiency in elderly anemic patients.

Anemia 2011 27;2011:925907. Epub 2011 Jul 27.

Department of Hematology, Uppsala University Hospital, 751 85 Uppsala, Sweden.

The aim of this study was to evaluate sensitivity and specificity for reticulocyte hemoglobin content (CHr) compared to other hematimetric and biochemical iron parameters, in particular, mean corpuscular hemoglobin (MCH), when screening for iron deficiency in elderly anemic patients. Bone marrow staining negative for iron was used as the gold standard criterion for iron deficiency anemia (IDA). Sensitivity and specificity for CHr, soluble transferrin receptor (sTfR), soluble transferrin receptor/log ferritin (TfR-F index), ferritin, MCH, and transferrin saturation were determined. The best cut-off point for CHr was 30.5 pg corresponding to a sensitivity and specificity of 93% and 69% for IDA, respectively. For MCH, a sensitivity of 93% and a specificity of 86%, respectively, correspond to an optimal cut-off of 28.5 pg. Analysis of CHr was not superior to MCH with respect to sensitivity and specificity when screening for IDA in elderly anemic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2011/925907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145342PMC
November 2011

Relation between brain interstitial and systemic glucose concentrations after subarachnoid hemorrhage.

J Neurosurg 2011 Jul 8;115(1):66-74. Epub 2011 Apr 8.

Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden.

Object: The aim in the present investigation was to study the relation between brain interstitial and systemic blood glucose concentrations during the acute phase after subarachnoid hemorrhage (SAH). The authors also evaluated the effects of insulin administration on local brain energy metabolism.

Methods: Nineteen patients with spontaneous SAH were prospectively monitored with intracerebral microdialysis (MD). The relation between plasma glucose and MD-measured interstitial brain glucose concentrations as well as the temporal pattern of MD glucose, lactate, pyruvate, glutamate, and glycerol was studied for 7 days after SAH. Using a target plasma glucose concentration of 5-10 mmol/L, the effect of insulin injection was also evaluated.

Results: The mean (± SD) correlation coefficient between plasma glucose and MD glucose was 0.27 ± 0.27 (p = 0.0005), with a high degree of individual variation. Microdialysis glucose, the MD/plasma glucose ratio, and MD glutamate concentrations decreased in parallel with a gradual increase in MD pyruvate and MD lactate concentrations. There were no significant changes in the MD L/P ratio or MD glycerol levels. Insulin administration induced a decrease in MD glucose and MD pyruvate.

Conclusions: After SAH, there was a positive correlation between plasma and MD glucose concentrations with a high degree of individual variation. A gradual decline in MD glucose and the MD/plasma glucose ratio and an increase in MD pyruvate and MD lactate concentrations during the 1st week after SAH suggest a transition to a hyperglycolytic state with increased cerebral glucose consumption. The administration of insulin was related to a lowering of MD glucose and MD pyruvate, often to low levels even though plasma glucose values remained above 6 mmol/L. After SAH, the administration of insulin could impede the glucose supply of the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2011.3.JNS10899DOI Listing
July 2011
-->