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  • 1.
    Andersson, Christoffer R.
    et al.
    Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Bergquist, Jonas
    Department of Chemistry (BMC), Analytical Chemistry and Neurochemistry, Uppsala University, Uppsala, Sweden.
    Theodorsson, Elvar
    Departments of Clinical Chemistry and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Department of Neurology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Comparisons between commercial salivary testosterone enzyme-linked immunosorbent assay kits2017In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 8, p. 582-586Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Measuring testosterone concentrations is of interest both in clinical situations and for research, the latter expanding rapidly during recent years. An increased demand for convenient methods has prompted a number of companies to develop enzyme-linked immunosorbent assay (ELISA) kits to measure testosterone concentrations in saliva. However, the inter-comparability of kits from different manufacturers have yet to be determined.

    AIM OF STUDY: The aim of this study was to compare commercially available ELISA kits from four different manufacturers (Salimetrics, IBL, DRG and Demeditec).

    METHODS: Saliva was collected from 50 participants (25 men and 25 women). Each sample was analysed by the four ELISA kits.

    RESULTS: The correlations between the ELISA kits from Demeditec, DRG and Salimetrics were moderate to high with r-values > .77; however, proportional errors between the methods calls for caution. The ELISA kit from IBL malfunctioned and no results from this kit was obtained.

    CONCLUSIONS: Results from studies using the ELISA kits from Demeditec, DRG and Salimetrics are generally comparable; however, translation using the formulae presented in the current study could increase the accuracy of these comparisons.

  • 2.
    Appelros, Peter
    et al.
    Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Háls Berglund, Maria
    Riksstroke, Medicincentrum, University Hospital of Norrland, Umeå, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Department of Clinical Chemistry, Linköping University, Linköping, Sweden.
    Long-Term Risk of Stroke after Transient Ischemic Attack2017In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 43, no 1-2, p. 25-30Article in journal (Refereed)
    Abstract [en]

    Background: In the absence of active management, the stroke risk after a transient ischemic attack (TIA) may be high. Almost 10 years ago, the results of the EXPRESS and SOS-TIA studies called for a more rapid management of TIA patients. The purpose of this study was to investigate the other stroke risks in the longer term, after the implementation of a more active approach to TIA. We also wanted to assess the predictive value of the ABCD2 score in this context.

    Methods: Riksstroke is the national stroke registry in Sweden. Data from Riksstroke's TIA module, and the national cause-of-death register, for the years 2011 and 2012 were used in this study. Stroke occurrence was monitored via Riksstroke. Cox's regression was used for risk evaluation. The predictive value of the ABCD2 score was assessed by calculating the area under the receiver operating characteristics curve.

    Results: A total of 15,068 TIA episodes occurred in 14,102 patients. The follow-up time varied between 0 and 819 days, with an average of 417 days. The mortality for all TIA patients during the follow-up time was 7.1%. Of the unique patients, 545 had one or more strokes (3.9%), corresponding to 34 events per 1,000 person years. Significant risk factors for stroke were: age, previous TIA, atrial fibrillation (AF), oral anticoagulant (OAC) treatment, hypertension treatment, and the ABCD2 items speech impairment, unilateral weakness, and diabetes mellitus. The ABCD2 score correlated with a subsequent stroke, but its predictive value was low.

    Conclusion: The risk of stroke is low after the acute phase of a TIA, probably lower than in previous studies. This may be due to better secondary prevention in recent years. Several risk factors predict stroke, notably hypertensive treatment, which may be inadequate; and AF, where OACs may be under-used. It is difficult to identify the role of the ABCD2 score in clinical practice.

  • 3.
    Boknäs, Niklas
    et al.
    Linköping University, Linköping, Sweden .
    Faxälv, Lars
    Linköping University, Linköping, Sweden .
    Ström, Jakob O.
    Linköping University, Linköping, Sweden .
    Tengvall, Pentti
    University of Gothenburg, Gothenburg, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden .
    Ramström, Sofia
    Linköping University, Linköping, Sweden .
    Lindahl, Tomas L.
    Linköping University, Linköping, Sweden .
    Platelets do not generate activated factor XII: how inappropriate experimental models have led to misleading conclusions2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 10, p. 1692-1694Article in journal (Refereed)
  • 4.
    Buchwald, Fredrik
    et al.
    Department of Clinical Sciences Neurology, Lund University, Lund, Sweden; Department of Neurology, Skåne University Hospital, Malmö, Sweden.
    Ström, Jakob O.
    Centre for Health Sciences, Örebro University Hospital, Örebro, Sweden.
    Norrving, Bo
    Department of Clinical Sciences Neurology, Lund University, Lund, Sweden; Department of Neurology, Skåne University Hospital, Malmö, Sweden.
    Petersson, Jesper
    Department of Clinical Sciences Neurology, Lund University, Lund, Sweden; Department of Neurology, Skåne University Hospital, Malmö, Sweden.
    Validation of Diagnoses of Transient Ischemic Attack in the Swedish Stroke Register (Riksstroke) TIA-Module2015In: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 45, no 1, p. 40-43Article in journal (Refereed)
    Abstract [en]

    Background: In 2010, the Swedish Stroke Register (Riksstroke; RS) established a module for transient ischemic attacks (RS-TIA). We report a diagnostic validation study of patients included in RS-TIA.

    Methods: During the first year, 7,825 patients were registered at 59 out of 74 Swedish hospitals. A time-based TIA definition was applied. A sample of 180 patients (30 patients each from 6 hospitals), with a similar distribution of age and sex as in RS-TIA, was prepared. Two independent observers assessed medical records for quality of documentation and assigned a diagnosis of likely, possible, unlikely TIA or ischennic stroke, according to pre-specified criteria.

    Results:The 2 observers agreed in 77% of cases that the event was a likely or possible TIA, in 3% that the event was an ischemic stroke, and in 2% that the event was an unlikely TIA. The observers disagreed in 8% of patients on TIA vs. ischennic stroke, and in 11% on a vascular vs. non-vascular cause. Quality of documentation was fair.

    Conclusions: There was interobserver agreement on diagnosis of TIA in the majority of patients included in RS-TIA. Diagnostic accuracy may be further improved by more systematic documentation of symptoms and signs.

  • 5.
    David, Fresnais
    et al.
    Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ingberg, Edvin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Infection.
    Elvar, Theodorsson
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Lack of association in acne and salivary testosterone2018In: Journal of controversies in biomedical research, ISSN 2205-5975, Vol. 4, no 1Article in journal (Refereed)
    Abstract [en]

    The pathogenesis of acne vulgaris has only been partially elucidated. Various hormones, especially androgens, are likely to play a role, but results of studies are still inconclusive. The objective of the current study was to investigate whether day to day variation in salivary testosterone correlates with acne in males. Saliva samples were collected for 120 consecutive days from each of the 40 males. Salivary testosterone concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Facial acne lesions were assessed on a daily basis by photography by the participating males. Potential confounders’ (sexual intercourse, masturbation, physical exercise and disease) were also registered every day by the participants. A significant but weak association between salivary testosterone and acne was found (n = 4602, r = 0.031, P = 0.034). Elevated testosterone concentrations were associated with an increase in acne, but when testosterone concentrations were above twice the individual average, acne lesions paradoxically decreased. The current results indicate that daily fluctuations in salivary testosterone levels in males are associated with acne patterns, but the weak correlation suggests that the effect is too small to be of clinical significance. The analysis in the current study was complicated by a large number of days on which the participants had no acne, as well as the seemingly non-monotonic relation between testosterone and acne. This may indicate that the actual relation is stronger than concluded here.

  • 6.
    Faxälv, Lars
    et al.
    Linköping University, Linköping, Sweden.
    Boknäs, Niklas
    Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Linköping University, Linköping, Sweden.
    Tengvall, Pentti
    Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Linköping University, Linköping, Sweden.
    Lindahl, Tomas L.
    Linköping University, Linköping, Sweden.
    Putting polyphosphates to the test: evidence against platelet-induced activation of factor XII2013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, no 23, p. 3818-3824Article in journal (Refereed)
    Abstract [en]

    The recent claim that stimulated platelets activate the intrinsic pathway of coagulation by the release of polyphosphates has been considered a breakthrough in hemostasis research. In little more than 3 years, the original publication by Müller et al has been cited >100 times. However, none of the citing articles has sought to independently validate this potentially paradigm-shifting concept. To this end, we performed extensive experimentation in vitro and in vivo in an attempt to verify the claim that factor XII (FXII) is primarily activated by stimulated platelets. In contrast to the original assertion, platelet-derived polyphosphates were found to be weak activators of FXII, with a FXIIa-generating activity of <10% compared with equivalent concentrations of kaolin. Using different coagulation assays, it was shown that platelet contribution to whole blood coagulation was unrelated to the generation of activated FXII in vitro. Additionally, key results used to verify the hypothesis in the original study in vivo were found to be irreproducible. We conclude that platelet-derived polyphosphates are not physiologically relevant activators of FXII.

  • 7.
    Ingberg, Edvin
    et al.
    Örebro University, School of Medical Sciences. Dept of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Dock, H.
    Dept of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Theodorsson, E.
    Dept of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Theodorsson, A.
    Dept of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Dept of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis2016In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 11, no SUPP 3, p. 108-108Article in journal (Other academic)
    Abstract [en]

    Background/Objectives: Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specific pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible.

    Design/Method: As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters' impact on infarct size variability and mortality.

    Results: The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality.

    Conclusions: Our study offers guidance for researchers striving to optimize mouse stroke models.

  • 8.
    Ingberg, Edvin
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Dock, Hua
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Theodorsson, Elvar
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Theodorsson, Annette
    Department of Neurosurgery and Department of Clinical and Experimental Medicine Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Effect of laser Doppler flowmetry and occlusion time on outcome variability and mortality in rat middle cerebral artery occlusion: inconclusive results2018In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 19, no 1, article id 24Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Stroke is among the leading causes of death and disability. Although intense research efforts have provided promising treatment options in animals, most clinical trials in humans have failed and the therapeutic options are few. Several factors have been suggested to explain this translational difficulty, particularly concerning methodology and study design. Consistent infarcts and low mortality might be desirable in some, but not all, studies. Here, we aimed to investigate whether the use of laser Doppler flowmetry (LDF) and the occlusion time (60 vs. 45 min) affected outcome variability and mortality in a rat stroke model. Eighty ovariectomized female Wistar rats were subjected to ischemic stroke using intraluminal filament middle cerebral artery occlusion with or without LDF and with occlusion times of 45 or 60 min. Outcome was evaluated by triphenyl tetrazolium chloride staining of brain slices to measure infarct size and a modified sticky tape test.

    RESULTS: Neither LDF nor occlusion times of 45 versus 60 min significantly affected mortality, outcome variability or outcome severity.

    CONCLUSIONS: Due to the unexpectedly high mortality and variability the statistical power was very low and thus the results were inconclusive.

  • 9.
    Ingberg, Edvin
    et al.
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Dock, Hua
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Theodorsson, Annette
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden; Division of Neuro and Inflammation Science, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Neurosurgery, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medicine, Örebro University, Sweden. Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden; Vårdvetenskapligt Forskningscentrum/Centre for Health Sciences, Örebro University Hospital, County Council of Örebro, Örebro, Sweden.
    Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 21086Article in journal (Refereed)
    Abstract [en]

    Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specific pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters' impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models.

  • 10.
    Ingberg, Edvin
    et al.
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Theodorsson, Elvar
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Theodorsson, Annette
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Neuroscience, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Neurosurgery, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Vårdvetenskapligt Forskningscentrum/Centre for Health Sciences, Örebro University Hospital, Region Örebro Län, Örebro, Sweden.
    Effects of high and low 17β-estradiol doses on focal cerebral ischemia in rats2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 20228Article in journal (Refereed)
    Abstract [en]

    The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17β-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17β-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17β-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17β-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17β-estradiol, the smaller the infarct.

  • 11.
    Ingberg, Edvin
    et al.
    Division of Microbiology, Linköping University, Linköping, Sweden; Molecular Medicine, Department of Clinical and Experimental Medicine, Department of Clinical Chemistry, Faculty of Health Sciences, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Gudjonsdottir, Johanna
    Division of Microbiology, Linköping University, Linköping, Sweden; Molecular Medicine, Department of Clinical and Experimental Medicine, Department of Clinical Chemistry, Faculty of Health Sciences, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Division of Microbiology, Linköping University, Linköping, Sweden; Molecular Medicine, Department of Clinical and Experimental Medicine, Department of Clinical Chemistry, Faculty of Health Sciences, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Theodorsson, Annette
    Division of Microbiology, Linköping University, Linköping, Sweden; Molecular Medicine, Department of Clinical and Experimental Medicine, Department of Clinical Chemistry, Faculty of Health Sciences, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Microbiology, Linköping University, Linköping, Sweden; Molecular Medicine, Department of Clinical and Experimental Medicine, Department of Clinical Chemistry, Faculty of Health Sciences, Center for Diagnostics, Region Östergötland, Linköping, Sweden; Örebro University Hospital, County Council of Örebro, Centre for Health Sciences (Vårdvetenskapligt Forskningscentrum), Örebro, Sweden.
    Elevated body swing test after focal cerebral ischemia in rodents: methodological considerations2015In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 16, article id 50Article in journal (Refereed)
    Abstract [en]

    Background: The elevated body swing test (EBST) is a behavioral test used to evaluate experimental stroke in rodents. The basic idea is that when the animal is suspended vertically by the tail, it will swing its head laterally to the left or right depending on lesion side. In a previous study from our lab using the EBST after middle cerebral artery occlusion (MCAo), rats swung contralateral to the infarct day 1 post-MCAo, but ipsilateral day 3 post-MCAo. This shift was unexpected and prompted us to perform the present study. First, the literature was systematically reviewed to elucidate whether a similar shift had been noticed before, and if consensus existed regarding swing direction. Secondly, an experiment was conducted to systematically investigate the suggested behavior. Eighty-three adult male and female Sprague-Dawley rats were subjected to MCAo or sham surgery and the EBST was performed up to 7 days after the lesion.

    Results: Both experimentally and through systematic literature review, the present study shows that the direction of biased swing activity in the EBST for rodents after cerebral ischemia can differ and even shift over time in some situations. The EBST curve for females was significantly different from that of males after the same occlusion time (p = 0.023).

    Conclusions: This study highlights the importance of adequate reporting of behavioral tests for lateralization and it is concluded that the EBST cannot be recommended as a test for motor asymmetry after MCAo in rats.

  • 12.
    Ingberg, Edvin
    et al.
    Linköping University, Linköping, Sweden.
    Theodorsson, A.
    Linköping University, Linköping, Sweden.
    Theodorsson, E.
    Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Linköping University, Linköping, Sweden.
    Methods for long-term 17β-estradiol administration to mice2012In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 175, no 1, p. 188-193Article in journal (Refereed)
    Abstract [en]

    Rodent models constitute a cornerstone in the elucidation of the effects and biological mechanisms of 17β-estradiol. However, a thorough assessment of the methods for long-term administration of 17β-estradiol to mice is lacking. The fact that 17β-estradiol has been demonstrated to exert different effects depending on dose emphasizes the need for validated administration regimens. Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17β-estradiol using one of the two commonly used subcutaneous methods; slow-release pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and silastic capsules (with/without convalescence period, silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 μg 17β-estradiol/mL sesame oil), or a novel peroral method (56 μg 17β-estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were used as ovariectomized and intact controls. Serum samples were obtained weekly for five weeks and 17β-estradiol concentrations were measured using radioimmunoassay. The peroral method resulted in steady concentrations within--except on one occasion--the physiological range and the silastic capsules produced predominantly physiological concentrations, although exceeding the range by maximum a factor three during the first three weeks. The 0.18 mg pellet yielded initial concentrations an order of magnitude higher than the physiological range, which then decreased drastically, and the 0.72 mg pellet produced between 18 and 40 times higher concentrations than the physiological range during the entire experiment. The peroral method and silastic capsules described in this article constitute reliable modes of administration of 17β-estradiol, superior to the widely used commercial pellets.

  • 13.
    Isaksson, Ida-Maria
    et al.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Ström, Jakob O.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Methods for 17β-oestradiol administration to rats.2011In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 71, no 7, p. 583-592Article in journal (Refereed)
    Abstract [en]

    Several studies indicate that the beneficial or harmful effects of oestrogens in stroke are dose-dependent. Rats are amongst the most frequently used animals in these studies, which calls for thoroughly validated methods for administering 17β-oestradiol to rats. In an earlier study we characterised three different administration methods for 17β-oestradiol over 42 days. The present study assesses the concentrations in a short time perspective, with the addition of a novel peroral method. Female Sprague-Dawley rats were ovariectomised and administered 17β-oestradiol by subcutaneous injections, silastic capsules, pellets and orally (in the nut-cream Nutella(®)), respectively. One group received 17β-oestradiol by silastic capsules without previous washout time. Blood samples were obtained after 30 minutes, 1, 2, 4, 8, 12, 24, 48 and 168 hours and serum 17β-oestradiol (and oestrone sulphate in some samples) was subsequently analysed. For long-term characterisation, one group treated perorally was blood sampled after 2, 7, 14, 21, 28, 35 and 42 days. At sacrifice, uterine horns were weighed and subcutaneous tissue samples were taken for histological assessment. The pellets, silastic capsule and injection groups produced serum 17β-oestradiol concentrations that were initially several orders of magnitude higher than physiological levels, while the peroral groups had 17β-oestradiol levels that were within the physiological range during the entire experiment. The peroral method is a promising option for administering 17β-oestradiol if physiological levels or similarity to women's oral hormone therapy are desired. Uterine weights were found to be a very crude measure of oestrogen exposure.

  • 14.
    Ivars, K.
    et al.
    Department of Clinical and Experimental Medicine, Division of Pediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Nelson, N.
    Department of Clinical and Experimental Medicine, Division of Pediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Pediatrics, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
    Theodorsson, A.
    Division of Neuroscience, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Neurosurgery, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Linköping, Sweden.
    Theodorsson, E.
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Ström, Jakob O.
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Mörelius, E.
    Department of Social and Welfare Studies, Division of Health, Activity and Care, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Erratum: Development of Salivary Cortisol Circadian Rhythm and Reference Intervals in Full-Term Infants2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, article id e0151888Article in journal (Other academic)
  • 15.
    Ivars, Katrin
    et al.
    Department of Pediatrics, Linköping University, Linköping, Sweden; Department of Clinical and Experiment al Medicine, Linköping University, Linköping, Sweden.
    Nelson, Nina
    Department of Pediatrics, Linköping University, Linköping, Sweden; Department of Clinical and Experiment al Medicine, Linköping University, Linköping, Sweden; Department of Quality and Patient Safety, Karolinska University Hospital, Stockholm, Sweden.
    Theodorsson, Annette
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Neurosurgery, Linköping University, Linköping, Sweden; Department of Pediatrics, Linköping University, Linköping, Sweden.
    Theodorsson, Elvar
    Department of Clinical Chemistry, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Linköping University, Linköping, Sweden; Department of Neurology, Faculty of Medicine and Health, University of Örebro, Örebro, Sweden.
    Morelius, Evalotte
    Division of Nursing Science, Department of Social and Welfare Studies, Linköping University, Norrköping, Sweden.
    Development of salivary cortisol circadian rhythm in preterm infants2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 8, article id e0182685Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate at what age preterm infants develop a salivary cortisol circadian rhythm and identify whether it is dependent on gestational age and/or postnatal age. To evaluate whether salivary cortisol circadian rhythm development is related to behavioral regularity. To elucidate salivary cortisol levels in preterm infants during the first year of life.

    Methods: This prospective, longitudinal study included 51 preterm infants. 130 healthy full-term infants served as controls. Monthly salivary cortisol levels were obtained in the morning (07:30-09:30), at noon (10:00-12:00), and in the evening (19:30-21:30), beginning at gestational age week 28-32 and continuing until twelve months corrected age. Behavioral regularity was studied using the Baby Behavior Questionnaire.

    Results: A salivary cortisol circadian rhythm was established by one month corrected age and persisted throughout the first year. The preterm infants showed a cortisol pattern increasingly more alike the full-term infants as the first year progressed. The preterm infants increase in behavioral regularity with age but no correlation was found between the development of salivary cortisol circadian rhythm and the development of behavior regularity. The time to establish salivary cortisol circadian rhythm differed between preterm and full-term infants according to postnatal age (p = 0.001) and was dependent on gestational age. Monthly salivary cortisol levels for preterm infants from birth until twelve months are presented. Additional findings were that topical corticosteroid medication was associated with higher concentrations of salivary cortisol (p = 0.02) and establishment of salivary cortisol circadian rhythm occurred later in infants treated with topical corticosteroid medication (p = 0.02).

    Conclusions: Salivary cortisol circadian rhythm is established by one month corrected age in preterm infants. Establishment of salivary cortisol circadian rhythm is related to gestational age rather than to postnatal age. Salivary cortisol circadian rhythm development is not related to behavioral regularity.

  • 16.
    Ivars, Katrin
    et al.
    Linköping University, Linköping, Sweden.
    Nelson, Nina
    Linköping University, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden; Operations and Specialty Surgery Center, Region County Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden; Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Ström, Jakob O.
    Linköping University, Linköping, Sweden; Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Mörelius, Evalotte
    Linköping University, Linköping, Sweden.
    Development of Salivary Cortisol Circadian Rhythm and Reference Intervals in Full-Term Infants2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6Article in journal (Refereed)
    Abstract [en]

    Background: Cortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life.

    Methods: 130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist.

    Results: A significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life.

    Conclusions: Cortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants.

  • 17.
    Paues, Jakob
    et al.
    University Hospital, Linköping, Sweden; Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    University Hospital, Linköping, Sweden; Linköping University, Linköping, Sweden.
    Eriksson, Lars
    University Hospital, Linköping, Sweden; Linköping University, Linköping, Sweden.
    Theodorsson, Annette
    University Hospital, Linköping, Sweden; Linköping University, Linköping, Sweden .
    Tuberculous meningitis with positive cell-count in lumbar puncture CSF though negative cell-count from ventricular drainage CSF2011In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 62, no 5, p. 404-405Article in journal (Refereed)
  • 18.
    Ruborg, Rebecca
    et al.
    Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Gunnarsson, Karin
    Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden; Department of Clinical Chemistry, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Neuro-och rehabmedicinska kliniken, Region Örebro Län, Örebro, Sweden.
    Predictors of post-stroke body temperature elevation2017In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 17, article id 218Article in journal (Refereed)
    Abstract [en]

    Background: Growing evidence indicates that elevated body temperature after stroke is associated with unfavorable outcome. The aim of the current study was to investigate which factors predict temperature elevation within 48 h of stroke onset. Specifically, we hypothesized that temperature elevation would be associated with stroke symptom severity and that hemorrhagic stroke would cause a more pronounced temperature increase compared to ischemic stroke.

    Methods: The medical records of 400 stroke patients were retrospectively reviewed. Multiple linear regression analysis was used to determine which factors were associated with elevated body temperature.

    Results: Several factors were significantly associated with peak body temperature (the highest recorded body temperature) within 48 h of stroke onset: stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS) (regression coefficient; (RC) 0.022), female gender (RC 0.157), tympanic/non-rectal temperature reading (RC -0.265), swallowing difficulties (RC 0.335), intubation (RC 0.470), antipyretic treatment (RC 0.563), and C-reactive protein > 50 or signs of infection at admission (RC 0.298). Contrary to our expectations, patients with intracerebral hemorrhage did not have higher peak body temperatures than patients with ischemic stroke.

    Conclusions: In conclusion, temperature elevation within the first 48 h of stroke onset is common, can be partially predicted using information at admission and is strongly associated with stroke severity. The strong association with stroke severity may, at least partly, explain the previously described association between post-stroke temperature elevation and unfavorable outcome.

  • 19.
    Slezak, Julia K.
    et al.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Theodorsson, Elvar
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Linköping University, Linköping, Sweden.
    Testosterone-like immunoreactivity in hair measured in minute sample amounts - a competitive radioimmunoassay with an adequate limit of detection2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17636Article in journal (Refereed)
    Abstract [en]

    The concentrations of testosterone deposited in hair during hair growth may provide a retrospective reflection of the concentrations of bioactive testosterone in plasma. The objective of this study was to develop a radioimmunoassay with a sufficiently low limit of detection to measure the testosterone-like immunoreactivity in smaller hair samples (5 mg) than used in earlier studies, and to compare three different extraction procedures. The competitive radioimmunoassay consisted of a polyclonal antiserum (immunogen testosterone-7 alpha-BSA) and a radioligand synthesised from testosterone-3-CMO-histamine. The within-assay and total coefficients of variation in the working range was 3% and 4.5%, respectively. The limit of detection was 0.87 pg/mL, which is equivalent to 0.12 pg/mg testosterone in 5 mg of hair. The concentration of testosterone-like immunoreactivity in hair samples was 1.23 (SD 0.47) pg/mg in women and 2.67 (SD 0.58) pg/mg in men (pulverised hair). Significantly improved precision was found when pulverised hair was used compared to non-pulverised hair. Our data indicate that pulverisation of the hair prior to hormone extraction is crucial. Detection limits fit for the intended purpose are achievable with 5 mg samples of hair.

  • 20.
    Ström, Jakob
    et al.
    Örebro University, School of Medical Sciences. Neurology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Appelros, Peter
    Neurology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Long term risk of stroke after transient ischemic attack2016In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 11, no SUPP 3, p. 218-218Article in journal (Other academic)
  • 21.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden .
    Boström, S.
    Linköping University, Linköping, Sweden.
    Bobinski, L.
    Umeå University, Umeå, Sweden.
    Theodorsson, A.
    Linköping University, Linköping, Sweden.
    Low-grade infection complicating silastic dural substitute 32 years post-operatively2011In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 25, no 2Article in journal (Refereed)
    Abstract [en]

    Background: A complication of a silastic dural substitute is described, which appeared after 32 years-by far the longest latency period reported in the literature.

    Methods: Case report and literature review.

    Results: In 1971, a 20-year old woman suffered from an acute subdural haematoma and a temporal cerebral contusion due to a motorbike accident. She underwent an operation with evacuation of these and the dura was mended with a silastic duraplasty. Thirty-two years later she deteriorated with increased memory problems and dysphasia. CT revealed an expanding haemorrhagic mass around the previous duraplasty, which demanded surgery with removal of the silastic dural implant and evacuation of the haemorrhagic mass. Although the haemorrhagic mass enveloped the silastic implant, a contribution of the acrylate flap cannot be ruled out. Bacteriological cultures revealed Acinetobacter spp. in the CSF. Adequate post-operative antibiotic treatment was administered. The patient slowly improved, but the complication represented a major setback in her long-term cognitive and communicative functions.

    Conclusions: This case widens the previously reported time-frame of late complications by 60%, from 20 to 32 years, and will hopefully serve to increase the awareness of late infections and haemorrhages induced by silastic dural implants, thereby improving diagnosis and treatment in future cases.

  • 22.
    Ström, Jakob O.
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Vårdvetenskapligt Forskningscent, Ctr Hlth Sci, Örebro Univ Hosp, Cty Council Örebro, Örebro, Sweden; Fac Hlth Sci, Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden.
    Ingberg, Edvin
    Örebro University Hospital. Clinical Chemistry, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Impact of methodology on estrogens' effects on cerebral ischemia in rats: an updated meta-analysis2014In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 15, article id 22Article in journal (Refereed)
    Abstract [en]

    Background: Although most animal stroke studies have demonstrated potent neuroprotective effects of estrogens, there are a number of articles reporting the opposite. In 2009, we made the case that this dichotomy was related to administered estrogen dose. Several other suggestions for the discordant results have also been propagated, including the age of the experimental animals and the length of hypoestrogenicity prior to estrogen administration. These two suggestions have gained much popularity, probably because of their kinship with the window of opportunity hypothesis, which is commonly used to explain the analogous dichotomy among human studies. We were therefore encouraged to perform an updated meta-analysis, and to improve it by including all relevant variables in a large multiple regression model, where the impact of confounders could be controlled for.

    Results: The multiple regression model revealed an indisputable impact of estrogen administration mode on the effects of estrogens in ischemic stroke. Subcutaneous slow-release pellets differed from the injection and silastic capsule treatments in terms of impact of estrogens on ischemic stroke, showing that the first mentioned were more prone to render estrogens damaging. Neither the use of elderly animals nor the adoption of longer wash-out periods influenced estrogens' effects on experimental ischemic stroke in rats.

    Conclusions: We conclude that the discordant results regarding estrogens' effects in rat models of ischemic stroke are a consequence of differences in estrogen administration modes. These results are not only of importance for the ongoing debate regarding menopausal hormone therapy, but also have an important bearing on experimental stroke methodology and the apparent translational roadblock for suggested stroke interventions.

  • 23.
    Ström, Jakob O.
    et al.
    Örebro University, School of Medical Sciences. Örebro University, School of Medical Sciences, Department of Neurology, Örebro, Sweden; Linköping University, Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping, Sweden .
    Ingberg, Edvin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Infectious Diseases.
    Slezak, Julia K.
    Linköping University, Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping, Sweden .
    Theodorsson, Annette
    Linköping University, Department of Neurosurgery and Department of Clinical and Experimental Medicine, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping, Sweden .
    Male Testosterone Does Not Adapt to the Partner's Menstrual Cycle2018In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 15, no 8, p. 1103-1110Article in journal (Refereed)
    Abstract [en]

    Background: It has not yet been established whether men in heterosexual relationships adapt their hormone levels to their female partner's menstrual cycle to allocate reproductive resources to the period when the female is actually fertile.

    Aim: This prospective observational study tested the hypothesis that some males have peaks in testosterone or acne (a possible biomarker for androgen activity) near their partners' ovulation, whereas other males display the opposite pattern.

    Methods: 48 couples supplied menstrual cycle data, male salivary samples, and a protocol of daily activities for 120 days. Daily saliva samples were analyzed for testosterone concentrations by enzyme-linked immunosorbent assay. The main hypothesis was tested by analyzing whether each individual male's testosterone/acne response to ovulation (either an increase or a decrease in comparison to the individual's average levels) was stable over time. To do this, we analyzed the Spearman correlation between individually normalized periovulatory testosterone and acne during the first half of the study versus the second half of the study.

    Outcomes: Correlation between each male individual's periovulatory testosterone and acne patterns during the first half of the study versus the second half of the study.

    Results: No predictability in the male individuals' testosterone (Spearman's rho = -0.018, P = .905) or acne (Spearman's rho = -0.036, P = .862) levels during ovulation was found.

    Clinical translation: The study being "negative," there is no obvious translational potential in the results.

    Strengths and limitations: The main strength of this study lies in the excellent compliance of the study participants and the large number of sampling timepoints over several menstrual cycles, thereby allowing each male individual to be his own control subject. A limitation is that samples were only obtained in the morning; however, including later timepoints would have introduced a number of confounders and would also have hampered the study's feasibility.

    Conclusions: The current results strongly indicate that male morning testosterone levels neither increase nor decrease in response to the partner's ovulation. This discordance to previous laboratory studies could indicate either that (i) the phenomenon of hormonal adaptation of men to women does not exist and earlier experimental studies should be questioned, (ii) that the phenomenon is short-lived/acute and wanes if the exposure is sustained, or (iii) that the male testosterone response may be directed toward other women than the partner. Copyright (C) 2018, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine.

  • 24.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden; County Council of Örebro, Örebro, Sweden.
    Nilsson, Tove
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Effects of 17β-estradiol on galanin(1-29)- and galanin(1-16)-like immunoreactivities2013In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 43, p. 1-7Article in journal (Refereed)
    Abstract [en]

    There are reasons to believe that the galanin neuropeptide family could include more than the two hitherto known members (galanin(1-29) and galanin-like peptide), such as the existence of at least three galanin receptors and the fact that synthetic short-chain homologues have effects and binding sites that are distinct from those of galanin(1-29). The current study uses a radioimmunoassay based on a polyclonal rabbit antiserum raised against galanin(1-16) to study the concentrations of galanin(1-16) like immunoreactivity (LI) in the various parts of the brain and gut of ovariectomized female rats, and investigates the effects of different concentrations of estradiol on these concentrations in relation to galanin(1-29)-LI. Galanin(1-29) concentrations were increased by 17β-estradiol administration in almost all examined tissues whereas galanin(1-16)-LI was increased by 17β-estradiol treatment in most of the gut, but only in the pituitary of the brain. Furthermore, the relation between galanin(1-29)-LI and galanin(1-16)-LI varied substantially from tissue to tissue. The main hypothesis, that galanin(1-16)-LI would be affected by 17β-estradiol in brain and/or gut, was confirmed in addition to the secondary hypothesis, stating that the pattern of galanin(1-16)-LI changes would differ from that of galanin(1-29). The study indicates that galanin(1-16)-LI is estrogen-responsive but that its concentrations are regulated differently from that of galanin(1-29). This is strongly indicative of a biological relevance of this potentially new member of the galanin neuropeptide family.

  • 25.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden.
    Strid, Tobias
    Linköping University, Linköping, Sweden.
    Hammarström, Sven
    Linköping University, Linköping, Sweden.
    Disruption of the alox5ap gene ameliorates focal ischemic stroke: possible consequence of impaired leukotriene biosynthesis2012In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 13, no 1, article id 146Article in journal (Refereed)
    Abstract [en]

    Background: Leukotrienes are potent inflammatory mediators, which in a number of studies have been found to be associated with ischemic stroke pathology: gene variants affecting leukotriene synthesis, including the FLAP (ALOX5AP) gene, have in human studies shown correlation to stroke incidence, and animal studies have demonstrated protective properties of various leukotriene-disrupting drugs. However, no study has hitherto described a significant effect of a genetic manipulation of the leukotriene system on ischemic stroke. Therefore, we decided to compare the damage from focal cerebral ischemia between wild type and FLAP knockout mice. Damage was evaluated by infarct staining and a functional test after middle cerebral artery occlusion in 20 wild type and 20 knockout male mice.

    Results: Mortality-adjusted median infarct size was 18.4 (3.2-76.7) mm3 in the knockout group, compared to 72.0 (16.7-174.0) mm3 in the wild type group (p < 0.0005). There was also a tendency of improved functional score in the knockout group (p = 0.068). Analysis of bone marrow cells confirmed that knockout animals had lost their ability to form leukotrienes.

    Conclusions: Since the local inflammatory reaction after ischemic stroke is known to contribute to the brain tissue damage, the group difference seen in the current study could be a consequence of a milder inflammatory reaction in the knockout group. Our results add evidence to the notion that leukotrienes are important in ischemic stroke, and that blocked leukotriene production ameliorates cerebral damage.

  • 26.
    Ström, Jakob O.
    et al.
    Institution of Clinical and Experimental Medicine/Department of Clinical Chemistry, Linköping University, Linköping, Sweden.
    Theodorsson, A.
    Institution of Clinical and Experimental Medicine/Department of Clinical Chemistry, Linköping University, Linköping, Sweden; Institution of Clinical and Experimental Medicine/Department of Neurosurgery, Linköping University, Linköping, Sweden.
    Theodorsson, E.
    Institution of Clinical and Experimental Medicine/Department of Clinical Chemistry, Linköping University, Linköping, Sweden.
    Hormesis and female sex hormones2011In: Pharmaceuticals, ISSN 1424-8247, E-ISSN 1424-8247, Vol. 4, no 5, p. 726-740Article, review/survey (Refereed)
    Abstract [en]

    Hormone replacement after menopause has in recent years been the subject of intense scientific debate and public interest and has sparked intense research efforts into the biological effects of estrogens and progestagens. However, there are reasons to believe that the doses used and plasma concentrations produced in a large number of studies casts doubt on important aspects of their validity. The concept of hormesis states that a substance can have diametrically different effects depending on the concentration. Even though estrogens and progestagens have proven prone to this kind of dose-response relation in a multitude of studies, the phenomenon remains clearly underappreciated as exemplified by the fact that it is common practice to only use one hormone dose in animal experiments. If care is not taken to adjust the concentrations of estrogens and progestagens to relevant biological conditions, the significance of the results may be questionable. Our aim is to review examples of female sexual steroids demonstrating bidirectional dose-response relations and to discuss this in the perspective of hormesis. Some examples are highlighted in detail, including the effects on cerebral ischemia, inflammation, cardiovascular diseases and anxiety. Hopefully, better understanding of the hormesis phenomenon may result in improved future designs of studies of female sexual steroids.

  • 27.
    Ström, Jakob O.
    et al.
    Linköping University Hospital, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University Hospital, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University Hospital, Linköping, Sweden.
    Dose-related neuroprotective versus neurodamaging effects of estrogens in rat cerebral ischemia: a systematic analysis2009In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 29, no 8, p. 1359-1372Article, review/survey (Refereed)
    Abstract [en]

    Numerous studies of the effects of estrogens for stroke prevention have yielded conflicting results in human and animal studies alike. We present a systematical analysis of study design and methodological differences between 66 studies where estrogens' impact on ischemic brain damage in rat models has been investigated, providing evidence that the differences in results may be explained by high estrogen doses produced by slow-release pellets. These pellets have been used in all studies showing increased neurologic damage because of estrogens. Our data indicate that the increased neurologic damage is related to the pellets' plasma concentration profile with an early, prolonged, supraphysiological peak. Neither the method of inducing the ischemic brain lesions, the choice of variables for measuring outcome, the measured plasma concentrations of estrogens at the time of ischemia nor rat population attributes (sex, strain, age, and diseases) are factors contributing to the discrepancies in results. This suggests that the effects of estrogens for stroke prevention are concentration related with a complex dose-response curve, and underscores the importance of carefully validating the experimental methods used. Future studies of hormone-replacement therapy in women may have to take dosage and administration regimens into account.

  • 28.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden; University Hospital, Linköping University, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden.
    Mechanisms of estrogens' dose-dependent neuroprotective and neurodamaging effects in experimental models of cerebral ischemia2011In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 12, no 3, p. 1533-1562Article, review/survey (Refereed)
    Abstract [en]

    Ever since the hypothesis was put forward that estrogens could protect against cerebral ischemia, numerous studies have investigated the mechanisms of their effects. Despite initial studies showing ameliorating effects, later trials in both humans and animals have yielded contrasting results regarding the fundamental issue of whether estrogens are neuroprotective or neurodamaging. Therefore, investigations of the possible mechanisms of estrogen actions in brain ischemia have been difficult to assess. A recently published systematic review from our laboratory indicates that the dichotomy in experimental rat studies may be caused by the use of insufficiently validated estrogen administration methods resulting in serum hormone concentrations far from those intended, and that physiological estrogen concentrations are neuroprotective while supraphysiological concentrations augment the damage from cerebral ischemia. This evidence offers a new perspective on the mechanisms of estrogens' actions in cerebral ischemia, and also has a direct bearing on the hormone replacement therapy debate. Estrogens affect their target organs by several different pathways and receptors, and the mechanisms proposed for their effects on stroke probably prevail in different concentration ranges. In the current article, previously suggested neuroprotective and neurodamaging mechanisms are reviewed in a hormone concentration perspective in an effort to provide a mechanistic framework for the dose-dependent paradoxical effects of estrogens in stroke. It is concluded that five protective mechanisms, namely decreased apoptosis, growth factor regulation, vascular modulation, indirect antioxidant properties and decreased inflammation, and the proposed damaging mechanism of increased inflammation, are currently supported by experiments performed in optimal biological settings.

  • 29.
    Ström, Jakob O.
    et al.
    Linköping University Hospital, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University Hospital, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University Hospital, Linköping, Sweden.
    Substantial discrepancies in 17beta-oestradiol concentrations obtained with three different commercial direct radioimmunoassay kits in rat sera2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 8, p. 806-813Article in journal (Refereed)
    Abstract [en]

    The extensive use of oestrogen for contraception and amelioration of post-menopausal symptoms has made it the subject of substantial recent research efforts, and ovariectomized (ovx) rats treated with exogenous ovarial hormones are important when investigating the effects and mechanisms of oestrogen actions. The crucial need to control and monitor plasma levels of 17beta-oestradiol calls for accurate, precise and robust assay methods. The performance of direct radioimmunoassays (RIAs) in measurement of 17beta-oestradiol has been reported previously for human samples, but to our knowledge not for rat samples. In the current study, 552 serum samples from ovx, native and hormone-treated rats were used to compare the performance of three commercially manufactured direct RIAs from the companies DPC (Siemens Healthcare Diagnostics Inc., formerly Diagnostic Products Corporation), DSL (Diagnostic Systems Labs) and MPB (MP Biomedicals, formerly ICN Biomedicals). Substantial differences in results between the three assay methods were found when measuring serum 17beta-oestradiol concentrations. The following formulas describing the relation between the different methods were obtained using weighted Deming's orthogonal regression (based on pg/mL): DSL = 0.43*DPC+12.3, MPB = 2.1*DPC+84.7 and DSL = 4.8*MPB+22.2. Furthermore, a preceding diethyl ether extraction step of the serum appears to impair the performance of the RIAs in the present samples (based on pg/mL): DPC(ex) = 0.39*DPC(unex)+0.76, DSL(ex) = 0.32*DSL(unex)-1.7 and MPB(ex) = 0.22*MPB(unex)+1.4.

  • 30.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden.
    Holm, Lovisa
    Linköping University, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden.
    Different methods for administering 17beta-estradiol to ovariectomized rats result in opposite effects on ischemic brain damage2010In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 11, article id 39Article in journal (Refereed)
    Abstract [en]

    Background: Numerous stroke studies have controversially shown estrogens to be either neuroprotective or neurodamaging. The discordant results observed in rat brain ischemia models may be a consequence of discrepancies in estrogen administration modes resulting in plasma concentration profiles far from those intended. To test this hypothesis we reproduced in detail and extended an earlier study from our lab using a different mode of 17beta-estradiol administration; home-made silastic capsules instead of commercial slow-release 17beta-estradiol pellets. Four groups of female rats (n = 12) were ovariectomized and administered 17beta-estradiol or placebo via silastic capsules. All animals underwent MCAo fourteen days after ovariectomy and were sacrificed three days later.

    Results: In contrast to our earlier results using the commercial pellets, the group receiving 17b-estradiol during the entire experiment had significantly smaller lesions than the group receiving placebo (mean ± SEM: 3.85 ± 0.70% versus 7.15 ± 0.27% of total slice area, respectively; p = 0.015). No significant neuroprotection was found when the 17b-estradiol was administered only during the two weeks before or the three days immediately after MCAo.

    Conclusions: The results indicate that different estrogen treatment regimens result in diametrically different effects on cerebral ischemia. Thus the effects of estrogens on ischemic damage seem to be concentration-related, with a biphasic, or even more complex, dose-response relation. These findings have implications for the design of animal experiments and also have a bearing on the estrogen doses used for peri-menopausal hormone replacement therapy.

  • 31.
    Ström, Jakob O.
    et al.
    Linköping University Hospital, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University Hospital, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University Hospital, Linköping, Sweden.
    Order of magnitude differences between methods for maintaining physiological 17beta-oestradiol concentrations in ovariectomized rats2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 8, p. 814-822Article in journal (Refereed)
    Abstract [en]

    The use of animal models, especially the rat, is crucial for elucidating the biological effects and mechanisms of the widely used hormone 17beta-oestradiol. Unfortunately, there is a lack of consensus on optimal means of obtaining and maintaining physiological 17beta-oestradiol concentrations in plasma and this may be the reason for the varying results in several studies, including the disagreement on whether 17beta-oestradiol is neuroprotective or not. Very few studies have been devoted to investigating the characteristics and biological relevance of different methods of 17beta-oestradiol administration. We therefore ovariectomized 75 Sprague-Dawley rats and, following a 2-week washout period, administered 17beta-oestradiol using three different methods; daily injections (10 microg 17beta-oestradiol/kg), slow-release pellets (0.25 mg 60 day-release pellets, 0.10 mg 90 day-release pellets) and silastic capsules (with/without washout periods) (silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with 20 mm columns of 180 microg 17beta-oestradiol/mL sesame oil). A further 45 animals were used as ovariectomized and native controls studied in different parts of the oestrous cycle. Silastic capsules produced concentrations of 17beta-oestradiol within the physiological range 4-5 weeks independently of whether a prior washout period was included or not. The slow-release pellets, irrespective of dose or release period, resulted in initial concentrations an order of magnitude above physiological concentrations during the first 2 weeks followed by a substantial decrease. Daily injections resulted in increasing 17beta-oestradiol concentrations, but within physiological levels. Silastic capsules are conveniently manufactured and used and are superior to pellets and injections in reliably producing long-term 17beta-oestradiol concentrations within the physiological range.

  • 32.
    Ström, Jakob
    et al.
    Örebro University, School of Medical Sciences. Centre for Health Sciences, Örebro University Hospital, Region Örebro Län, Örebro, Sweden; Department of Neurology, Örebro University Hospital, Region Örebro Län, Örebro, Sweden.
    Tavosian, A.
    Department of Neurology, Örebro University Hospital, Region Örebro Län, Örebro, Sweden.
    Appelros, Peter
    Department of Neurology, Örebro University Hospital, Region Örebro Län, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Cardiovascular risk factors and TIA characteristics in 19,872 Swedish TIA patients2016In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 134, no 6, p. 427-433Article in journal (Refereed)
    Abstract [en]

    Background: Transient ischemic attack (TIA) constitutes a major risk factor for stroke, making TIA patients an important group for secondary intervention. The aim of this study was to account for risk factor prevalence in TIA patients and analyze the association between TIA characteristics and risk factors.

    Methods: We included 20,871 TIA events in 19,872 patients who were registered in the Swedish Riksstroke registry during the years 2010 through 2012. Data from other Swedish registers were used for comparison. The following variables were analyzed: age, sex, diabetes mellitus, atrial fibrillation (AF), cigarette smoking, and antihypertensive treatment.

    Results: Compared to the general population (based on data retrieved from Sweden's national public health survey Health on equal terms'), TIA patients more often had diabetes mellitus (prevalence ratio, PR = 2.3), AF without oral anticoagulants (OAC) (PR = 2.8), and AF on OAC (PR = 1.6). Blood pressure medication was less prevalent among TIA patients than in the general population (PR = 0.57). Increasing age was associated with longer attacks.

    Conclusions: The fact that diabetes mellitus, atrial fibrillation, and smoking are more common in TIA patients than in the general population suggests that these factors are risk factors for TIA, even if causal relations cannot be proven. The relation between increasing age and longer attacks possibly reflects an increased proportion of embolic TIAs, or impaired recovery ability. Our results also suggest a significant proportion of untreated hypertension cases in the population.

  • 33.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Ingberg, Edvin
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Druvefors, Emma
    Ryhov County Hospital, County Council of Jönköping, Jönköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    The female menstrual cycle does not influence testosterone concentrations in male partners2012In: Journal of Negative Results in Biomedicine, ISSN 1477-5751, E-ISSN 1477-5751, Vol. 11, p. 1-7, article id 1Article in journal (Refereed)
    Abstract [en]

    Background: The time of ovulation has since long been believed to be concealed to male heterosexual partners. Recent studies have, however, called for revision of this notion. For example, male testosterone concentrations have been shown to increase in response to olfactory ovulation cues, which could be biologically relevant by increasing sexual drive and aggressiveness. However, this phenomenon has not previously been investigated in real-life human settings. We therefore thought it of interest to test the hypothesis that males' salivary testosterone concentrations are influenced by phases of their female partners' menstrual cycle; expecting a testosterone peak at ovulation.

    Methods: Thirty young, healthy, heterosexual couples were recruited. During the course of 30-40 days, the women registered menses and ovulation, while the men registered sexual activity, physical exercise, alcohol intake and illness (confounders), and obtained daily saliva samples for testosterone measurements. All data, including the registered confounders, were subjected to multiple regression analysis.

    Results: In contrast to the hypothesis, the ovulation did not affect the testosterone levels, and the resulting testosterone profile during the menstrual cycle was on the average flat. The specific main hypothesis, that male testosterone levels on the day of ovulation would be higher than day 4 of the cycle, was clearly contradicted by a type II error(β)-analysis (< 14.3% difference in normalized testosterone concentration; β = 0.05).

    Conclusions: Even though an ovulation-related salivary testosterone peak was observed in individual cases, no significant effect was found on a group level.

  • 34.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Ingberg, Edvin
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden; Department of Clinical and Experimental Medicine, Neurosurgery, Faculty of Health Sciences, Linköping University, County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Method parameters' impact on mortality and variability in rat stroke experiments: a meta-analysis2013In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 14, article id 41Article in journal (Refereed)
    Abstract [en]

    Background: Even though more than 600 stroke treatments have been shown effective in preclinical studies, clinically proven treatment alternatives for cerebral infarction remain scarce. Amongst the reasons for the discrepancy may be methodological shortcomings, such as high mortality and outcome variability, in the preclinical studies. A common approach in animal stroke experiments is that A) focal cerebral ischemia is inflicted, B) some type of treatment is administered and C) the infarct sizes are assessed. However, within this paradigm, the researcher has to make numerous methodological decisions, including choosing rat strain and type of surgical procedure. Even though a few studies have attempted to address the questions experimentally, a lack of consensus regarding the optimal methodology remains.

    Methods: We therefore meta-analyzed data from 502 control groups described in 346 articles to find out how rat strain, procedure for causing focal cerebral ischemia and the type of filament coating affected mortality and infarct size variability.

    Results: The Wistar strain and intraluminal filament procedure using a silicone coated filament was found optimal in lowering infarct size variability. The direct and endothelin methods rendered lower mortality rate, whereas the embolus method increased it compared to the filament method.

    CONCLUSIONS: The current article provides means for researchers to adjust their middle cerebral artery occlusion (MCAo) protocols to minimize infarct size variability and mortality.

  • 35.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Ingberg, Edvin
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Effects of high and low 17β-estradiol doses on focal cerebral ischemia: negative results2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, article id 3111Article in journal (Refereed)
    Abstract [en]

    The reasons why some animal studies indicate that estrogens increase focal cerebral ischemic damage while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. Recent evidence indicates that discrepancies in hormone administration paradigms, resulting in highly different serum hormone concentrations, may account for the dichotomy. The current study aimed to test this hypothesis. Sixty ovariectomized female rats were randomized into three groups differing in 17β-estradiol regimens, and transient focal cerebral ischemia was subsequently induced. All animals were subjected to a small functional testing battery, and three days after MCAo they were sacrificed for infarct size assessment. Infarct sizes did not differ between groups, however clear discrepancies were seen in body weight and feeding behavior. In comparison to sham-operated animals, ovariectomized rats rapidly increased in body weight, whereas the opposite was seen in rats receiving 17beta-estradiol. The weight gain in the ovariectomized rats was paralleled by an increased food intake.

  • 36.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden.
    Ingberg, Edvin
    Linköping University, Linköping, Sweden.
    Isaksson, Ida-Maria
    Linköping University, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden.
    Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration2012In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 64, article id e4013Article in journal (Refereed)
    Abstract [en]

    Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures.

  • 37.
    Tavosian, Alborz
    et al.
    Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Appelros, Peter
    Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Incidence of Transient ischemic Attacks in Sweden2016In: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 47, no 1, p. 20-25Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: Stroke incidence may be on the decline in high-income countries. There may have been a shift from severe forms of cerebrovascular disease to less severe forms. No study regarding transient ischemic attack (TIA) incidence has been performed in Sweden since the 1980s.

    Methods: We used 2011 and 2012 data from the Swedish stroke register. A large proportion of Sweden's 72 hospitals took part in the TIA register, meaning that 63 (2011) and 66 (2012) percent of the entire population were studied.

    Results: The number of TIA-cases was 13,880. The number of first ever TIA cases was 9098, 4,675 in men, and 4,423 in women, comprising 66% of all TIAs. The crude overall IR for first ever TIA was 74 per 100,000. The age- and sex-standardized IRs were 73 per 100,000 when standardized to the European population of 2013, and 47 per 100,000 when standardized to the European population 1976.

    Conclusions: The TIA incidence in Sweden is high, and no decline is seen when compared with previous studies. Better prevention may have caused a shift from severe forms of cerebrovascular disease to less severe forms. Fordemographic reasons, the health services will most likely face an increasing number of TIA patients in the coming years.

  • 38.
    Vigren, P.
    et al.
    Linköping University Hospital, Linköping, Sweden.
    Ström, Jakob O.
    Linköping University, Linköping, Sweden.
    Petrini, P.
    Karolinska University Hospital, Stockholm, Sweden.
    Callander, M.
    Linköping University, Linköping, Sweden.
    Theodorsson, A.
    Linköping University Hospital, Linköping, Sweden.
    Treatment of spontaneous intracerebral haemorrhage in Glanzmann's thrombasthenia2012In: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 18, no 5, p. e381-e383Article in journal (Refereed)
  • 39.
    Wästfelt, Maja
    et al.
    Örebro University, School of Medical Sciences. Department of Neurology.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Department of Neurology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Clinical Chemistry, Institution of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Predictors of post-stroke fever and infections: a systematic review and meta-analysis2018In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 18, article id 49Article, review/survey (Refereed)
    Abstract [en]

    Background: Fever after stroke is common, and often caused by infections. In the current study, we aimed to test the hypothesis that pneumonia, urinary tract infection and all-cause fever (thought to include at least some proportion of endogenous fever) have different predicting factors, since they differ regarding etiology.

    Methods: PubMed was searched systematically for articles describing predictors for post-stroke pneumonia, urinary tract infection and all-cause fever. A total of 5294 articles were manually assessed; first by title, then by abstract and finally by full text. Data was extracted from each study, and for variables reported in 3 or more articles, a meta-analysis was performed using a random effects model.

    Results: Fifty-nine articles met the inclusion criteria. It was found that post stroke pneumonia is predicted by age OR 1.07 (1.04-1.11), male sex OR 1.42 (1.17-1.74), National Institutes of Health Stroke Scale (NIHSS) OR 1.07 (1.05-1.09), dysphagia OR 3.53 (2.69-4.64), nasogastric tube OR 5.29 (3.01-9.32), diabetes OR 1.15 (1.08-1.23), mechanical ventilation OR 4.65 (2.50-8.65), smoking OR 1.16 (1.08-1.26), Chronic Obstructive Pulmonary Disease (COPD) OR 4.48 (1.82-11.00) and atrial fibrillation OR 1.37 (1.22-1.55). An opposite relation to sex may exist for UTI, which seems to be more common in women.

    Conclusions: The lack of studies simultaneously studying a wide range of predictors for UTI or all-cause fever calls for future research in this area. The importance of new research would be to improve our understanding of fever complications to facilitate greater vigilance, monitoring, prevention, diagnosis and treatment.

  • 40.
    Zsuzsanna Balla, Hajnal
    et al.
    Department of Neurology Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Theodorsson, Elvar
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Department of Neurology Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Evaluation of commercial, wireless dermal thermometers for surrogate measurements of core temperature2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Article in journal (Refereed)
    Abstract [en]

    Extensive research has been devoted to developing methods for assessing core body temperature, and to determine which method is most accurate. A number of wireless dermal thermometers for home use are presently available, but their relation to core body temperature and suitability for use in clinical research has hitherto not been assessed. The current study aimed to evaluate such thermometers by comparing them to the results of a rectal thermometer. Four wireless dermal thermometers for home use (FeverSmart, iThermonitor, Quest Temp Sitter, and Thermochron iButton) were applied to 15 patients during 24 h, and rectal temperature was measured at four occasions. Pearson correlation revealed moderate correlation for the Feversmart (r = 0.75), iThermonitor (r = 0.79), and Thermochron iButton (r = 0.71) systems. The Quest Temp Sitter system malfunctioned repeatedly, and the correlation (r = 0.29) for this method should therefore be assessed with caution. All dermal thermometers rendered lower average temperatures than Terumo c405 (Feversmart -0.70 ± 0.65 °C; iThermonitor -0.77 ± 0.53 °C, Quest Temp Sitter -1.18 ± 0.66 °C, and Thermochron iButton -0.87 ± 0.65 °C). Sensitivity of the dermal thermometers for detecting core temperatures ≥38.0 °C was low, ranging from 0.33 to 0.6, but improved to 0.60 to 0.80 after adjusting temperatures by the methods' average deviation from rectal temperature. The results from the dermal thermometers tested here showed an insufficient correlation to core temperature to be used for core temperature monitoring in clinical research and practice. Unfortunately, other options for non-invasive temperature measurements are few. The two thermometers with the least unsatisfactory performance profile in our evaluations were the Feversmart and iThermonitor systems.

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