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1.
  • Pettersson, Jonas, et al. (author)
  • Muscular exercise can cause highly pathological liver function tests in healthy men.
  • 2008
  • In: British Journal of Clinical Pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 65:2, s. 253-259
  • Journal article (peer-reviewed)abstract
    • What is already known about this subject • The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. • Physical exercise can result in transient elevations of liver function tests. • There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. What this study adds • Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. • Liver function tests are significantly increased for at least 7 days after weightlifting. • It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. Aim To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Methods Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10–12 days postexercise. Results Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, γGT and ALP remained within the normal range. Conclusion The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.
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2.
  • Torngren, Kristina, et al. (author)
  • Association of coronary calcium score with endothelial dysfunction and arterial stiffness
  • 2020
  • In: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 313, s. 70-75
  • Journal article (peer-reviewed)abstract
    • Background and aims: The aim of the study was to determine potential associations between endothelial dysfunction and arterial stiffness, measured by peripheral arterial tonometry, and coronary artery calcium score (CACS) assessed by computed tomography (CT). Methods and results: The BIG3 study is a prospective longitudinal, non-interventional, pulmonary-cardiovascular cohort study exploring the three major smoking-induced diseases: cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer, in a 45–75 aged cohort (mean 62 years), enriched in smokers. Computed tomography of the chest with assessment of CACS was performed in a selected subset of the participants (n = 2080). Peripheral arterial tonometry (EndoPAT) was used to assess endothelial function and arterial stiffness measured as reactive hyperaemia index (RHI) and augmentation index (AI), respectively. We observed significant associations of CACS, endothelial dysfunction, and arterial stiffness with several risk factors for coronary heart disease including age, sex, BMI, diabetes mellitus, and blood pressure. There was significant association of CACS, classified into three levels of severity, with RHI and AI (p = 0.0005 and p = 0.0009, respectively). For groups of increasing CACS (0, 1–400 and > 400 Agatston score), RHI decreased from median 1.89 (1.58–2.39), and 1.93 (1.62–2.41) to 1.77 (1.51–2.10). AI increased from median 14.3 (5.7–25.2), and 16.4 (8.1–27.6) to 18.0 (9.1–29.2). RHI, but not AI, remained significantly associated with CACS after risk factors adjustment. Conclusions: In this large study of coronary artery calcium and vascular function, we found an association between CACS and both endothelial dysfunction and arterial stiffness, indicating that they may reflect similar mechanisms for development of cardiovascular disease.
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3.
  • Wollmer, Per, et al. (author)
  • Within-session reproducibility of forced oscillometry
  • 2021
  • In: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 41:5, s. 401-407
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The forced oscillation technique (FOT) provides detailed information about the mechanics of the respiratory system, while requiring minimal co-operation by the patient. FOT may be abnormal in subjects with normal spirometry and appears to be more closely related to airway symptoms. It is, therefore, attractive in epidemiological studies, where a large number of different examinations are made in each subjects in a short period of time. Current technical standards recommend the mean of three consecutive measurements to be used, but there is limited information regarding within-session variability of FOT measurements.OBJECTIVE: The purpose of this study was to examine the within-session variability in FOT measurements in a large, population-based sample.METHODS: We performed three consecutive FOT measurements in 700 subjects using the impulse oscillometry system. The first measurement was compared to the mean of three measurements for resistance at 5 and 20 Hz (R5 and R20, respectively), R5-R20, reactance at 5 Hz (X5) and resonant frequency (fres ).RESULTS: The differences between the first and the mean of three measurements (median, interquartile range) were minimal, for example 0.002, -0.008 to 0.014 kPa L-1 s for R5 and -0.001, -0.008 to 0.005 kPa L-1 s for X5. Findings were numerically similar for men and women as well as for subjects with and without airflow obstruction at spirometry.CONCLUSIONS: We conclude that, whereas in clinical situations, three FOT measurements are to be preferred, a single measurement may suffice in epidemiological studies.
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4.
  • Ahlqvist, Emma, et al. (author)
  • Novel subgroups of adult-onset diabetes and their association with outcomes : a data-driven cluster analysis of six variables
  • 2018
  • In: The Lancet Diabetes and Endocrinology. - 2213-8587 .- 2213-8595. ; 6:5, s. 361-369
  • Journal article (peer-reviewed)abstract
    •  BackgroundDiabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis.MethodsWe did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of β-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations.FindingsWe identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes.InterpretationWe stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes.
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5.
  • Arner, Anders, et al. (author)
  • Calcium transients and the effect of a photolytically released calcium chelator during electrically induced contractions in rabbit rectococcygeus smooth muscle
  • 1998
  • In: Biophysical Journal. - 1542-0086 .- 0006-3495. ; 75:4, s. 1895-1903
  • Journal article (peer-reviewed)abstract
    • Intracellular Ca2+ was determined with the fura-2 technique during electrically induced contractions in the rabbit rectococcygeus smooth muscle at 22 degreesC. The muscles were electrically activated to give short, reproducible contractions. Intracellular [Ca2+] increased during activation; the increase in [Ca2+] preceded force development by approximately 2 s. After cessation of stimulation Ca2+ fell, preceding the fall in force by approximately 4 s. The fluorescence properties of fura-2 were determined with time-resolved spectroscopy using synchrotron light at the MAX-storage ring, Lund, Sweden. The fluorescence decay of free fura-2 was best described by two exponential decays (time constants approximately 0.5 and 1.5 ns) at low Ca2+ (pCa 9). At high Ca2+ (pCa 4.5), fluorescence decay became slower and could be fitted by one exponential decay (1.9 ns). Time-resolved anisotropy of free fura-2 was characteristic of free rotational motion (correlation time 0.3 ns). Motion of fura-2 could be markedly inhibited by high concentrations of creatine kinase. Time-resolved spectroscopy measurements of muscle fibers loaded with fura-2 showed that the fluorescence lifetime of the probe was longer, suggesting an influence of the chemical environment. Anisotropy measurements revealed, however, that the probe was mobile in the cells. The Ca2+-dependence of contraction and relaxation was studied using a photolabile calcium chelator, diazo-2, which could be loaded into the muscle cells in a similar manner as fura-2. Photolysis of diazo-2 leads to an increase in its Ca2+-affinity and a fall in free Ca2+. When muscles that had been loaded with diazo-2 were illuminated with UV light flashes during the rising phase of contraction, the rate of contraction became slower, suggesting a close relation between intracellular Ca2+ and the cross-bridge interaction. In contrast, photolysis during relaxation did not influence the rate of force decay, suggesting that relaxation of these contractions is not determined by the rate of Ca2+ removal or due to an increased Ca2+ sensitivity, but instead is limited by other processes such as deactivation by dephosphorylation or detachment of tension-bearing cross-bridges, possibly regulated by thin filament systems.
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6.
  • Arner, Anders, et al. (author)
  • Cross-bridge cycling in smooth muscle: a short review
  • 1998
  • In: Acta Physiologica Scandinavica. - 0001-6772. ; 164:4, s. 363-372
  • Journal article (peer-reviewed)abstract
    • This review is focused on the cross-bridge interaction of the organized contractile system of smooth muscle fibres. By using chemically skinned preparations the different enzymatic reactions of actin-myosin interaction have been associated with mechanical events. A rigor state has been identified in smooth muscle and the binding of ATP causes dissociation of rigor cross-bridges at rates slightly slower than those in skeletal muscle, but fast enough not to be rate-limiting for cross-bridge turn over in the muscle fibre. The release of inorganic phosphate (Pi) is associated with force generation, and this process is not rate-limiting for maximal shortening velocity (Vmax) in the fully activated muscle. The binding of ADP to myosin is strong in the smooth muscle contractile system, a property that might be associated with the generally slow cross-bridge turn over. Both force and Vmax are modulated by the extent of myosin light chain phosphorylation. Low levels of activation are considered to be associated with the recruitment of slowly cycling dephosphorylated cross-bridges which reduces shortening velocity. The attachment of these cross-bridge states in skinned smooth muscles can be regulated by cooperative mechanisms and thin filament associated systems. Smooth muscles exhibit a large diversity in their Vmax and the individual smooth muscle tissue can alter its Vmax under physiological conditions. The diversity and the long-term modulation of phenotype are associated with changes in myosin heavy and light chain isoform expression.
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7.
  • Arner, Anders, et al. (author)
  • Effects of Ca2+ on force-velocity characteristics of normal and hypertrophic smooth muscle of the rat portal vein
  • 1985
  • In: Acta Physiologica Scandinavica. - 0001-6772. ; 124:4, s. 525-533
  • Journal article (peer-reviewed)abstract
    • Portal hypertension was induced in rats by partial ligation of the hepatic branches of the portal vein. After 5 days of hypertension the portal veins were taken out and mounted for isometric and quick-release experiments. Portal veins from sham-operated normal rats served as controls. The ligated veins had an increased cross-sectional area, indicating smooth-muscle hypertrophy. Although the absolute magnitude of active force of these veins was increased, the active force per cross-sectional area was decreased, indicating an alteration in the properties of the contractile system. No difference in the Ca2+ concentration-response relations to K+-activated intact control and hypertrophic veins was found. In chemically skinned preparations, devoid of functional plasma membranes, the hypertrophic veins had similar Ca2+ sensitivity (in the presence of I microM calmodulin) but a lower force per cross-sectional area. Force-velocity relations were determined in K+-activated intact preparations. In control veins a reduction in extracellular Ca2+ was associated with a significant reduction in both isometric force and maximal shortening velocity (Vmax). In hypertrophic veins the decreased isometric force at maximal activation was associated with a low Vmax. A comparison between hypertrophic and submaximally stimulated control vessels showed corresponding Vmax and isometric force values. We conclude that the low isometric force of hypertrophic veins is associated with a lower rate of cross-bridge turnover. This could be an effect of alterations in the activation mechanisms or in the intrinsic properties of the contractile system itself.
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8.
  • Arner, Anders, et al. (author)
  • Energy turnover and lactate dehydrogenase activity in detrusor smooth muscle from rats with streptozotocin-induced diabetes
  • 1993
  • In: Acta Physiologica Scandinavica. - 0001-6772. ; 147:4, s. 375-383
  • Journal article (peer-reviewed)abstract
    • Force generation and tissue glucose metabolism were measured in the urinary bladder smooth muscle from rats with streptozotocin-induced diabetes (7-8 wk duration). Bladder wet wt was almost 4-fold higher in the diabetic animals compared with the untreated controls. Morphological analysis showed that the growth was associated with hypertrophy of the smooth muscle component in the bladder wall. Force generation of isolated bladder strip preparations was measured in vitro at different ambient oxygen tensions. Activation of intramural nerves, with electrical field stimulation, induced contractions that were unaffected by reduction of oxygen tension down to PO2 100 mmHg for both control and diabetic muscle strips. At zero PO2 force was reduced by approximately 10-20%, in both groups. High-K+ solution induced 'tonic' contractions that were slightly more inhibited by lowering PO2. At intermediate PO2 (between 100 and 20 mmHg) the diabetic muscle gave slightly higher force. At zero PO2 no significant difference could be detected between strips from control and diabetic animals. Oxygen consumption and lactate production in the preparations were determined at a PO2 of 290 mmHg and related to the volume of smooth muscle. At zero PO2, lactate formation increased 3- to 4-fold. The metabolic tension cost was lower at zero PO2. No differences in basal and contraction related metabolic rates could be detected between the two groups under normoxic and anoxic conditions. The maximal activity of lactate dehydrogenase (LDH) determined in tissue samples was about 2-fold higher in the diabetic bladder muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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9.
  • Arner, Anders, et al. (author)
  • Metabolism and force in hypertrophic smooth muscle from rat urinary bladder
  • 1990
  • In: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 258:5 Pt 1, s. 923-932
  • Journal article (peer-reviewed)abstract
    • Ten days of urinary outlet obstruction in the rat induced a threefold increase in bladder weight. Active force of control and hypertrophic bladder muscle strips was measured at varying PO2 levels after high-K+, carbachol, or electrical field stimulation. Highest force output was obtained with carbachol. Force per muscle area was lower in the hypertrophic muscles. The basal rates of oxygen consumption and lactate formation were similar in the two groups. The metabolic tension cost (ATP turnover/active force) was similar in the two groups for activation with high K+ and carbachol. In anoxia the active force decreased, but this was less pronounced in the hypertrophied muscle. Hypertrophied muscle could, in contrast to the controls, maintain a sustained K+ contracture in anoxia. Basal metabolic rates and tension cost were markedly reduced in anoxia for both groups. The lower force per area with unaltered tension cost, in hypertrophic muscles under all experimental conditions, may reflect unaltered intrinsic properties of the contractile system, although the amount of contractile material has decreased relative to cell volume. The increased resistance to anoxia may reflect a metabolic adaptation to impaired oxygen supply to the hypertrophied tissue.
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10.
  • Arner, Anders, et al. (author)
  • Structural and mechanical adaptations in rat aorta in response to sustained changes in arterial pressure
  • 1984
  • In: Acta Physiologica Scandinavica. - 0001-6772. ; 122:2, s. 119-126
  • Journal article (peer-reviewed)abstract
    • Structural and mechanical adaptations in response to sustained changes in arterial pressure were studied on abdominal aorta of the male rat. Two models were used: 1. Aortic ligature (L), immediately below the renal arteries producing hypotension distal to the knot (duration before sacrifice 6 weeks or 3 months). 2. One-clip renal hypertensive rats (H) (duration 6 weeks). Normotensive sham-operated rats (C) served as controls. At sacrifice mean tail artery pressure was L: 58 +/- 1, C: 110 +/- 3, and H: 163 +/- 5 mmHg (SE, N=6). Segments of abdominal aorta were mounted in vitro for determination of their length-tension relations (activation: High-K+ solution with 2.5 mM Ca2+). At end of experiments the vessels were supramaximally stimulated at optimal circumference (1o) for active force (activation: High-K+ solution with 10 mM Ca2+, and 10(-5) M noradrenaline), and then fixated for light and electron microscopy. Passive and active length-tension relations were shifted towards lower and higher circumference values for hypo- and hypertensive vessels, respectively. The 1o values were L: 3.60 +/- 0.13, C: 4.44 +/- 0.19, and H: 4.91 +/- 0.29 mm. The media thickness at 1o was reduced in L: 56.0 +/- 3.3, and increased in H: 81.3 +/- 2.4 compared to C: 73.4 +/- 1.8 micron. Maximal active wall stress was L: 46.6 +/- 9.8, C: 74.2 +/- 7.0, and H: 83.8 +/- 7.7 mN/mm2. Intracellular volume (ICV) in the media was L: 30 +/- 2, C: 45 +/- 3, and H: 44 +/- 1% (n=4 for each).
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11.
  • Bjork, Jonas, et al. (author)
  • COVID-19 vaccine effectiveness against severe disease from the Omicron BA.1 and BA.2 subvariants: surveillance results from southern Sweden, December 2021 to March 2022
  • 2022
  • Other publication (other academic/artistic)abstract
    • We compared vaccine effectiveness (VE) against severe COVID-19 during calendar periods from December 2021 to March 2022 when Omicron BA.1 and BA.2, respectively, were the dominating virus variants in Scania county, Sweden. We used continuous density case-control sampling matched for sex and age, and with further adjustment for differences in comorbidities and prior infection. VE remained relatively stable after the transition from BA.1 to BA.2 among people with at least three doses but decreased markedly among those with only two doses. Protection from prior infection was also lower after the transition to BA.2. These findings suggest that booster vaccination is needed to maintain sufficient protection against severe COVID-19.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was supported by Swedish Research Council (VR; grant numbers 2019-00198 and 2021-04665), Sweden's Innovation Agency (Vinnova; grant number 2021-02648) and by internal grants for thematic collaboration initiatives at Lund University held by JB and MI. FK is supported by grants from the Swedish Research Council and Governmental Funds for Clinical Research (ALF), and CB is supported by Swedish Research Council for Health, Working life and Welfare (Forte; grant number 2020-00962). The funders played no role in the design of the study, data collection or analysis, decision to publish, or preparation of the manuscript.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethical approval was obtained from the Swedish Ethical Review Authority (2021-00059).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAggregated surveillance data from the present study are publicly available.https://sodrasjukvardsregionen.se/kliniskastudier/covid-vacciner-skyddseffekt/
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12.
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13.
  • Björk, Jonas, et al. (author)
  • Effectiveness of the BNT162b2 vaccine in preventing COVID-19 in the working age population – first results from a cohort study in Southern Sweden
  • 2021
  • Other publication (other academic/artistic)abstract
    • Background Vaccine effectiveness against COVID-19 needs to be assessed in diverse real-world population settings.Methods A cohort study of 805 741 residents in Skåne county, Southern Sweden, aged 18-64 years, of whom 26 587 received at least one dose of the BNT162b2 vaccine. Incidence rates of COVID-19 were estimated in sex- and age-adjusted analysis and stratified in two-week periods with substantial community spread of the disease.Results The estimated vaccine effectiveness in preventing infection ≥7 days after second dose was 86% (95% CI 72-94%) but only 42% (95% CI 14-63%) ≥14 days after a single dose. No difference in vaccine effectiveness was observed between females and males. Having a prior positive test was associated with 91% (95% CI 85 to 94%) effectiveness against new infection among the unvaccinated.Conclusion A satisfactory effectiveness of BNT162b2 after the second dose was suggested, but with possibly substantially lower effect before the second dose.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was supported by an internal grant for thematic collaboration initiatives at Lund University held by JB, and by Swedish Research Council (VR; grant number 2019-00198). FK is supported by grants from the Swedish Research Council and Governmental Funds for Clinical Research (ALF). The funders played no role in the design of the study, data collection or analysis, decision to publish, or preparation of the manuscript.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethical approval was obtained from the Swedish Ethical Review Authority (2021-00059). As the study is register-based, individual participant consent was not necessary.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe dataset used in the present study is hosted by Scania county council, Sweden. Legal and ethical restrictions prevent public sharing of the dataset. Data can be made available for collaborations upon request to interested researchers but would generally require a new ethical permission.
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14.
  • Björk, Jonas, et al. (author)
  • High level of protection against COVID-19 after two doses of BNT162b2 vaccine in the working age population–first results from a cohort study in Southern Sweden
  • 2022
  • In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 54:2, s. 128-133
  • Journal article (peer-reviewed)abstract
    • Background: Vaccine effectiveness against COVID-19 needs to be assessed in diverse real-world population settings. Methods: A cohort study of 805,741 residents in Skåne county, Southern Sweden, aged 18–64 years, of whom 26,587 received at least one dose of the BNT162b2 vaccine. Incidence rates of COVID-19 were estimated in sex- and age-adjusted analysis and stratified in two-week periods with substantial community spread of the disease. Results: The estimated vaccine effectiveness in preventing infection ≥7 days after second dose was 86% (95% CI 72–94%) but only 42% (95% CI 14–63%) ≥14 days after a single dose. No difference in vaccine effectiveness was observed between females and males. Having a prior positive test was associated with 91% (95% CI 85–94%) effectiveness against new infection among the unvaccinated. Conclusion: A satisfactory effectiveness of BNT162b2 after the second dose was suggested, but with possibly substantially lower effect before the second dose.
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15.
  • Björk, Jonas, et al. (author)
  • Surveillance of COVID-19 vaccine effectiveness : A real-time case-control study in southern Sweden
  • 2022
  • In: Epidemiology and Infection. - 0950-2688. ; 150
  • Journal article (peer-reviewed)abstract
    • The extensive register infrastructure available for coronavirus disease 2019 surveillance in Scania county, Sweden, makes it possible to classify individual cases with respect to hospitalisation and disease severity, stratify on time since last dose and demographic factors, account for prior infection and extract data for population controls automatically. In the present study, we developed a case-control sampling design to surveil vaccine effectiveness (VE) in this ethnically and socioeconomically diverse population with more than 1.3 million inhabitants. The first surveillance results show that estimated VE against hospitalisation and severe disease 0-3 months after the last dose remained stable during the study period, but waned markedly 6 months after the last dose in persons aged 65 years or over.
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16.
  • Boels, P J, et al. (author)
  • Structure and mechanics of growing arterial microvessels from hypertrophied urinary bladder in the rat
  • 1994
  • In: Pflügers Archiv. - 0031-6768. ; 426:6, s. 506-515
  • Journal article (peer-reviewed)abstract
    • Rat bladder hypertrophy, induced by a partial ligation of the urethra, was used to study the accompanying changes of microvascular smooth muscle mechanics, pharmacology and morphology. A segment of a microarterial vessel to the bladder was taken from a defined anatomical location and studied in a wire myograph in vitro at the length for maximal isometric force development (Lmax). After 10 days of ligation, bladder hypertrophy resulted in a microvascular growth response compared to non-operated controls which was characterized by (i) an increase of the calculated diameter at Lmax from 134 +/- 5 microns to 222 +/- 19 microns; (ii) an increase of the media thickness from 22.4 +/- 1.9 microns to 32.2 +2- 3.0 microns; (iii) an increase of the active tension from 1.42 +/- 0.28 mN/mm to 3.06 +/- 0.33 mN/mm; (iv) no change of the wall/lumen ratio (from 0.83 +/- 0.10 to 0.79 +/- 0.15). Normalized length/force relations (active, passive and total) did not differ significantly between microarteries from control and hypertrophic bladders. Microvascular smooth muscle growth was also associated with a decreased sensitivity to K(+)-induced depolarization and an increased sensitivity to alpha 1-adrenergic stimulation. No differences were noted regarding the Ca2+ sensitivity of force during K(+)-induced depolarization. The results suggest that microvascular growth (1) is immediately and positively influenced by the organ growth; (2) results in a functional resetting of the microvascular segments towards larger diameters without gross morphological or mechanical alterations; and (3) is accompanied by pharmacological alterations of the smooth muscle reactivity.
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17.
  • Bonnevier, Johan, et al. (author)
  • Sustained norepinephrine contraction in the rat portal vein is lost when Ca(2+) is replaced with Sr(2+).
  • 2002
  • In: American Journal of Physiology: Cell Physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 282:4, s. 845-852
  • Journal article (peer-reviewed)abstract
    • Agonist-induced activation of smooth muscle involves a rise in intracellular Ca(2+) concentration and sensitization of myosin light chain phosphorylation to Ca(2+). Sr(2+) can enter through Ca(2+) channels, be sequestered and released from sarcoplasmic reticulum, and replace Ca(2+) in activation of myosin light chain phosphorylation. Sr(2+) cannot replace Ca(2+) in facilitation of agonist-activated Ca(2+)-dependent nonselective cation channels. It is not known whether Sr(2+) can replace Ca(2+) in small G protein-mediated sensitization of phosphorylation. To explore mechanisms involved in alpha-receptor-activated contractions in smooth muscle, effects of replacing Ca(2+) with Sr(2+) were examined in rat portal vein. Norepinephrine (NE) at
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18.
  • Börjesson, Fredrik, 1965- (author)
  • Approaches to Modularity in Product Architecture
  • 2012
  • Licentiate thesis (other academic/artistic)abstract
    • Modular product architecture is characterized by the existence of standardized interfaces between the physical building blocks. A module is a collection of technical solutions that perform a function, with interfaces selected for company-specific strategic reasons. Approaches to modularity are the structured methods by which modular product architectures are derived. The approaches include Modular Function Deployment (MFD), Design Structure Matrix (DSM), Function Structure Heuristics and many other, including hybrids. The thesis includes a survey of relevant theory and a discussion of four challenges in product architecture research, detailed in the appended papers. One common experience from project work is structured methods such as DSM or MFD often do not yield fully conclusive results. This is usually because the algorithms used to generate modules do not have enough relevant data. Thus, we ask whether it is possible to introduce new data to make the output more conclusive. A case study is used to answer this question. The analysis indicates that with additional properties to capture product geometry, and flow of matter, energy, or information, the output is more conclusive. If product development projects even have an architecture definition phase, very little time is spent actually selecting the most suitable tool. Several academic models are available, but they use incompatible criteria, and do not capture experience-based or subjective criteria we may wish to include. The research question is whether we can define selection criteria objectively using academic models and experience-based criteria. The author gathers criteria from three academic models, adds experience criteria, performs a pairwise comparison of all available criteria and applies a hierarchical cluster analysis, with subsequent interpretation. The resulting evaluation model is tested on five approaches to modularity. Several conclusions are discussed. One is that of the five approaches studied, MFD and DSM have the most complementary sets of strengths and weaknesses, and that hybrids between these two fundamental approaches would be particularly interesting. The majority of all product development tries to improve existing products. A common criticism against all structured approaches to modularity is they work best for existing products. Is this perhaps a misconception? We ask whether MFD and DSM can be used on novel product types at an early phase of product development. MFD and DSM are applied to the hybrid drive train of a Forwarder. The output of the selected approaches is compared and reconciled, indicating that conclusions about a suitable modular architecture can be derived, even when many technical solutions are unknown. Among several conclusions, one is the electronic inverter must support several operating modes that depend on high-level properties of the drive train itself (such as whether regeneration is used). A modular structure for the electronic inverter is proposed. Module generation in MFD is usually done with Hierarchical Cluster Analysis (HCA), where the results are presented in the form of a Dendrogram. Statistical software can generate a Dendrogram in a matter of seconds. For DSM, the situation is different. Most available algorithms require a fair amount of processing time. One popular algorithm, the Idicula-Gutierrez-Thebeau Algorithm (IGTA), requires a total time of a few hours for a problem of medium complexity (about 60 components). The research question is whether IGTA can be improved to execute faster, while maintaining or improving quality of output. Two algorithmic changes together reduce execution time required by a factor of seven to eight in the trials, and improve quality of output by about 15 percent.
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19.
  • Chen, Y, et al. (author)
  • Increase in insulin-like growth factor I in hypertrophying smooth muscle
  • 1994
  • In: American Journal of Physiology - Endocrinology and Metabolism. - 1522-1555. ; 266:2 Pt 1, s. 224-229
  • Journal article (peer-reviewed)abstract
    • The present study focuses on the role of the insulin-like growth factor (IGF) system in the development of smooth muscle hypertrophy. Hypertrophy was initiated by partial ligation of portal vein or urethra in female Sprague-Dawley rats weighing approximately 220 g. Levels of mRNA were analyzed by solution hybridization. Seven days after ligation, the wet weight of the portal vein was increased about threefold and the concentration of IGF-I mRNA was increased fourfold. The bladder wet weight was increased twofold 3 days after ligation and fourfold 10 days after ligation. IGF-I mRNA in the bladder was elevated 3-fold after 3 days and 2.5-fold after 10 days, whereas IGF binding protein 2 mRNA was increased approximately 2-fold after 3 days and 5-fold after 10 days. IGF-I receptor mRNA in the hypertrophying bladder remained unchanged. Increased levels of IGF-I were demonstrated with immunohistochemistry in both hypertrophying portal vein and urinary bladder. The results show a specific increase in IGF-I mRNA as well as an increased IGF-I immunoreactivity during hypertrophy of smooth muscle, which suggests that the local IGF-system may play a role in smooth muscle hypertrophy.
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20.
  • Digard, Helena, et al. (author)
  • Determination of Nicotine Absorption from Multiple Tobacco Products and Nicotine Gum
  • 2013
  • In: Nicotine & Tobacco Research. - : Oxford University Press (OUP). - 1469-994X .- 1462-2203. ; 15:1, s. 255-261
  • Journal article (peer-reviewed)abstract
    • Snus is a smokeless tobacco product traditionally used in Scandinavia and available in pouched or loose forms. The objective of this study was to determine nicotine absorption for current pouched and loose snus products in comparison with a cigarette and an over-the-counter nicotine gum. We conducted an open-label, randomized, 6-way, crossover study involving 20 healthy snus and cigarette users. One of 6 products (2 pouched snus, 2 weights of loose snus, a cigarette, and a nicotine gum) was administered at each of 6 visits. Blood samples were taken at intervals over 120 min and sensory perception assessed by questionnaire. For the 4 smokeless tobacco products and the nicotine gum, blood plasma levels of nicotine were ranked according to total nicotine content as follows: loose snus (27.1 mg nicotine) > pouched snus (14.7 mg nicotine) > loose snus (10.8 mg nicotine) = pouched snus (10.7 mg nicotine) > nicotine gum (4.2 mg nicotine). The area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C-max) of nicotine ranged from 26.9 to 13.1 ng.h/ml and 17.9 to 9.1 ng.h/ml, respectively across all the products. Nicotine was absorbed more rapidly from the cigarette but systemic exposure was within the range of the smokeless tobacco products (AUC = 14.8 ng.h/ml; C-max = 12.8 ng.h/ml). This study has generated new information on comparative nicotine absorption from a cigarette, loose snus, and pouched snus typical of products sold in Scandinavia. The similar nicotine absorption for 1 g portions of loose and pouched snus with approximately 11 mg of nicotine indicate that absorption kinetics were dependent on quantity of tobacco by weight and total nicotine content rather than product form.
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21.
  • Fritz, Örjan, et al. (author)
  • Bjurkärr – en småländsk bokskog med unika lavar och svampar.
  • 2014
  • In: Svensk Botanisk Tidskrift. - 0039-646X. ; 108:3–4, s. 2-18
  • Journal article (peer-reviewed)abstract
    • The old beech forest (250–300 yr) at Bjurkärr (core area 30 ha) in the province of Småland, S Sweden, was surveyed for epiphytic lichens of conservation concern in 1993–94. Several rare red-listed lichens were recorded, many with large populations. In 2011 the most endangered lichens were resurveyed due to the incorporation of Bjurkärr in the forthcoming national park of Lake Åsnen. Most species of the 1993–94 survey were rediscovered, whereas some apparently had vanished as a result of substrate decomposition. In addition, ten more red-listed lichens were recorded in 2011, e.g., Arthonia arthonioides and Collema fragrans. We also recorded Biatora ligni-mollis, not previously reported from Sweden. In all, 39 red-listed lichens are currently known from the area. Few areas in Sweden host such a large number of red-listed epiphytic lichens. In addition, the wood-inhabiting fungi on beech logs and snags were surveyed in 2011. The content of dead wood was high. A large number of red-listed or otherwise interesting wood-inhabiting fungi were recorded, e.g., Hericium erinaceus. Eleven fungal indicator species for valuable beech forests in Europe were recorded, the highest number for any Swedish beech forest. Factors explaining the high number of species of conservation concern include the long continuity of old, often slow-growing and damaged trees, the favourable geographical position in south Sweden, the suitable microclimate caused by the large neighboring lake and the exemption from modern forestry.
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22.
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23.
  • Hjortswang, Henrik, et al. (author)
  • Contractile properties of ureters from rats with infravesical urinary outlet obstruction
  • 1998
  • In: Urological Research. - : Springer Science and Business Media LLC. - 0300-5623 .- 1434-0879. ; 26:5, s. 337-342
  • Journal article (peer-reviewed)abstract
    • Mechanical properties of ureters from rats with infravesical urinary outflow obstruction were studied in vitro. Urinary outflow obstruction was created by partial ligation of the urethra in female rats. After 10 days a marked hypertrophy of the urinary bladder and a dilatation of the ureters were observed. Proximal and distal segments of the ureters from these animals were isolated and mounted in a wire myograph for force registration. Comparisons were made with ureters from control rats. The ureters from the rats with urinary outflow obstruction exhibited a large increase in lumen diameter and an unchanged thickness of the muscle layer. These data suggest that the dilatation of the ureters is associated with growth of the smooth muscle in the wall. All ureter preparations were relaxed in normal physiological salt solution. When the extracellular K+ concentration was increased to 20 mM the dilated ureters became spontaneously active. At [K+] in the range 20-40 mM in the presence of noradrenaline (10(-5) M) all ureters exhibited high-frequency spontaneous contractions. The dilated ureters had a lower frequency of spontaneous contractions and a higher force. The results show a pronounced remodelling of the ureter wall following infravesical outlet obstruction. The structural changes were associated with alterations in the contraction pattern of the preparations, most probably reflecting changes in the excitation-contraction coupling of the growing cells.
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24.
  • Håkansson, Anders, et al. (author)
  • Distribution of intranasal naloxone to potential opioid overdose bystanders in Sweden : Effects on overdose mortality in a full region-wide study
  • 2024
  • In: BMJ Open. - 2044-6055. ; 14:1
  • Journal article (peer-reviewed)abstract
    • Objectives Distribution of take-home naloxone is suggested to reduce opioid-related fatalities, but few studies have examined the effects on overdose deaths in the general population of an entire community. This study aimed to assess the effects on overdose deaths of a large-scale take-home naloxone programme starting in June 2018, using an observational design with a historic control period. Design From the national causes of death register, deaths diagnosed as X42 or Y12 (International Classification of Diseases, 10th revision, ICD-10) were registered as overdoses. Numbers of overdoses were calculated per 100 000 inhabitants in the general population, and controlled for data including only individuals with a prior substance use disorder in national patient registers, to focus on effects within the primary target population of the programme. The full intervention period (2019-2021) was compared with a historic control period (2013-2017). Setting Skåne county, Sweden. Participants General population. Interventions Large-scale take-home naloxone distribution to individuals at risk of overdose. Primary and secondary outcome measures Decrease in overdose deaths per 100 000 inhabitants, in total and within the population with substance use disorder diagnosis. Results Annual average number of overdose deaths decreased significantly from 3.9 to 2.8 per 100 000 inhabitants from the control period to the intervention period (a significant decrease in men, from 6.7 to 4.3, but not in women, from 1.2 to 1.3). Significant changes remained when examining only prior substance use disorder patients, and decreases in overdose deaths could not be attributed to a change in treatment needs for opioid use disorders in healthcare and social services. Conclusions The present study, involving 3 years of take-home naloxone distribution, demonstrated a decreased overdose mortality in the population, however, only in men. The findings call for further implementation of naloxone programmes, and for further studies of potential effects and barriers in women. Trial registration number NCT03570099.
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25.
  • Kahn, Fredrik, et al. (author)
  • Previous SARS-CoV-2 infections and their impact on the protection from reinfection during the Omicron BA.5 wave - a nested case-control study among vaccinated adults in Sweden.
  • 2024
  • In: IJID regions. - 2772-7076. ; 10, s. 235-239
  • Journal article (peer-reviewed)abstract
    • We evaluated the protection afforded by SARS-CoV-2 infection-induced immunity against reinfection among working-age vaccinated individuals during a calendar period from June to December 2022 when Omicron BA.5 was the dominating subvariant in Scania County, Sweden.The study cohort (n = 71,592) mainly consisted of health care workers. We analyzed 4144 infected cases during the Omicron BA.5 dominance and 41,440 sex- and age-matched controls with conditional logistic regression.The average protection against reinfection was marginal (16%, 95% confidence interval [CI] 7-23%) during the study period but substantially higher for recent infections. Recent infection (3-6 months) with Omicron BA.2 and BA.5 offered strong protection (86%, 95% CI 68-94% and 78%, 95% CI 69-84%), whereas more distant infection (6-12 months) with Omicron BA.1, BA.2, and the variants before Omicron offered marginal or no protection.These findings suggest that infection-induced immunity contributes to short-term population protection against infection with the subvariant BA.5 among working-age vaccinated individuals but wanes considerably with time, independent of the virus variant.
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26.
  •  
27.
  • Karlström, Gunnar, et al. (author)
  • MOLCAS : a program package for computational chemistry
  • 2003
  • In: Computational materials science. - 0927-0256 .- 1879-0801. ; 28:2, s. 222-239
  • Journal article (peer-reviewed)abstract
    • The program system MOLCAS is a package for calculations of electronic and structural properties of molecular systems in gas, liquid, or solid phase. It contains a number of modern quantum chemical methods for studies of the electronic structure in ground and excited electronic states. A macromolecular environment can be modeled by a combination of quantum chemistry and molecular mechanics. It is further possible to describe a crystalline material using model potentials. Solvent effects can be treated using continuum models or by combining quantum chemical calculations with molecular dynamics or Monte-Carlo simulations. MOLCAS is especially adapted to treat systems with a complex electronic structure, where the simplest quantum chemical models do not work. These features together with the inclusion of relativistic effects makes it possible to treat with good accuracy systems including atoms from the entire periodic system. MOLCAS has effective methods for geometry optimization of equilibria, transition states, conical intersections, etc. This facilitates studies of excited state energy surfaces, spectroscopy, and photochemical processes.
  •  
28.
  • Korsgren, Magnus, et al. (author)
  • Clinical efficacy and pharmacokinetic profiles of intranasal and oral cetirizine in a repeated allergen challenge model of allergic rhinitis.
  • 2007
  • In: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 98:4, s. 316-321
  • Journal article (peer-reviewed)abstract
    • Background: Intranasal and oral antihistamines are effective in treating allergic rhinitis. Studies comparing these routes of administration of an antihistamine regarding efficacy and pharmacokinetic profile are lacking. Objective: To compare topical and oral routes of administration of cetirizine regarding efficacy, plasma exudation, and systemic drug levels in a repeated allergen challenge model of allergic rhinitis. Methods: Oral cetirizine dihydrochloride, 10 mg once daily, and topical cetirizine dinitrate in a dose corresponding to 4.4 mg of the dihydrochloride salt twice daily were given to grass pollen-sensitive individuals for 12 days in a double-blind, placebo-controlled, crossover design. Timothy grass pollen allergen challenges were given once daily for 7 days using a nasal spray device. Nasal symptoms and peak inspiratory flow were recorded in the morning, 10 minutes after allergen challenge, and in the evening. The pharmacokinetics of the treatments was monitored in 8 patients. The remaining 28 patients were challenged topically with histamine 12 and 24 hours after the final topical and oral cetirizine doses, respectively. Nasal lavage levels of alpha(2)-macroglobulin were determined to evaluate histamine-induced mucosal plasma exudation. Results: During the last 3 days of the repeated allergen challenge model, chronic symptoms were established. Both treatments reduced symptoms 10 minutes after allergen challenge (P < .001 vs placebo). Neither treatment reduced morning and evening symptoms or nasal peak inspiratory flow. Topical, but not oral, cetirizine reduced histamine-induced plasma exudation (P < .01 vs placebo) when systemic drug levels were similar in the 2 treatment regimens. Conclusions: Topical and oral cetirizine reduced acute nasal symptoms produced by allergen challenges in patients with established chronic symptoms. There were also antihistaminic effects of topical cetirizine not related to systemic drug levels.
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29.
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30.
  • Lindqvist, Anders, et al. (author)
  • Long-term effects of Ca(2+) on structure and contractility of vascular smooth muscle
  • 1999
  • In: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 277:1, s. 64-73
  • Journal article (peer-reviewed)abstract
    • Culture of dispersed smooth muscle cells is known to cause rapid modulation from the contractile to the synthetic cellular phenotype. However, organ culture of smooth muscle tissue, with maintained extracellular matrix and cell-cell contacts, may facilitate maintenance of the contractile phenotype. To test the influence of culture conditions, structural, functional, and biochemical properties of rat tail arterial rings were investigated after culture. Rings were cultured for 4 days in the absence and presence of 10% FCS and then mounted for physiological experiments. Intracellular Ca(2+) concentration ([Ca(2+)](i)) after stimulation with norepinephrine was similar in rings cultured with and without FCS, whereas force development after FCS was decreased by >50%. The difference persisted after permeabilization with beta-escin. These effects were associated with the presence of vasoconstrictors in FCS and were dissociated from its growth-stimulatory action. FCS treatment increased lactate production but did not affect ATP, ADP, or AMP contents. The contents of actin and myosin were decreased by culture but similar for all culture conditions. There was no effect of FCS on calponin contents or myosin SM1/SM2 isoform composition, nor was there any appearance of nonmuscle myosin. FCS-stimulated rings showed evidence of cell degeneration not found after culture without FCS or with FCS + verapamil (1 microM) to lower [Ca(2+)](i). The decreased force-generating ability after culture with FCS is thus associated with increased [Ca(2+)](i) during culture and not primarily caused by growth-associated modulation of cells from the contractile to the synthetic phenotype.
  •  
31.
  • Löfgren, Mia, et al. (author)
  • Substrate and product dependence of force and shortening in fast and slow smooth muscle
  • 2001
  • In: Journal of General Physiology. - : Rockefeller University Press. - 0022-1295 .- 1540-7748. ; 117:5, s. 407-418
  • Journal article (peer-reviewed)abstract
    • To explore the molecular mechanisms responsible for the variation in smooth muscle contractile kinetics, the influence of MgATP, MgADP, and inorganic phosphate (P(i)) on force and shortening velocity in thiophosphorylated "fast" (taenia coli: maximal shortening velocity Vmax = 0.11 ML/s) and "slow" (aorta: Vmax = 0.015 ML/s) smooth muscle from the guinea pig were compared. P(i) inhibited active force with minor effects on the V(max). In the taenia coli, 20 mM P(i) inhibited force by 25%. In the aorta, the effect was markedly less (< 10%), suggesting differences between fast and slow smooth muscles in the binding of P(i) or in the relative population of P(i) binding states during cycling. Lowering of MgATP reduced force and V(max). The aorta was less sensitive to reduction in MgATP (Km for Vmax: 80 microM) than the taenia coli (Km for Vmax: 350 microM). Thus, velocity is controlled by steps preceding the ATP binding and cross-bridge dissociation, and a weaker binding of ATP is not responsible for the lower V(max) in the slow muscle. MgADP inhibited force and V(max). Saturating concentrations of ADP did not completely inhibit maximal shortening velocity. The effect of ADP on Vmax was observed at lower concentrations in the aorta compared with the taenia coli, suggesting that the ADP binding to phosphorylated and cycling cross-bridges is stronger in slow compared with fast smooth muscle.
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32.
  • Malmqvist, Cecilia, 1965-, et al. (author)
  • Survival, early growth and impact of damageby late‑spring frost and winter desiccation on Douglas‑firseedlings in southern Sweden
  • 2018
  • In: New forests. - : Springer. - 0169-4286 .- 1573-5095. ; 49:6, s. 723-736
  • Journal article (peer-reviewed)abstract
    • Introduction of non-native species, such as Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco), can be a means of mitigating the effects of climate change by meeting the growing demand for biomass and high quality wood. The aim of this study was to investigate early growth, survival and damage from late-spring frost and winter desiccation. A provenance trial with four coastal and three interior provenances of Douglas-fir originating from British Columbia, Canada, was established in Southwest Sweden (56°43′N, 13°08′E). Seedling height, length of the leading shoot, and occurrence of frost damage, were measured after one, three, and six growing seasons. Timing of bud break in spring was also observed. The interior Douglas-fir were more frequently damaged by late-spring frost compared to the coastal Douglas-fir. The interior Douglas-fir still had a higher survival after six growing seasons compared to the coastal variety. All provenances were damaged by winter desiccation, but the provenances originating from the coastal area were more severely damaged. Choice of variety may reduce the risk for either late-spring frost or winter desiccation.
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33.
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34.
  • Malmqvist, Ulf, et al. (author)
  • Contractile and cytoskeletal proteins in smooth muscle during hypertrophy and its reversal
  • 1991
  • In: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 260:5, s. 1085-1093
  • Journal article (peer-reviewed)abstract
    • Hypertrophy of rat urinary bladder smooth muscle was induced by partial urethral obstruction. Bladder weight increased from 70 to 240 mg after 10 days and to 700 mg after 7 wk. Removal of the obstruction after 10 days caused a regression of bladder weight to 130 mg. The relative volume of smooth muscle in the bladder wall increased during hypertrophy. The concentration of myosin in the smooth muscle cells decreased in 10-day hypertrophied bladders, whereas the concentration of actin was unchanged. The actin-myosin ratio was 2.3 in controls, 3.3 in 10-day obstructed bladders, and 2.9 in 7-wk obstructed bladders. After removal of obstruction, the ratio was normalized. Two isoforms of myosin heavy chains were identified (SM1 and SM2). The relative amount of SM2 decreased during hypertrophy. The relative proportion of actin isoforms (alpha, beta, and gamma) was altered toward more gamma and less alpha. These changes were reversible upon removal of the obstruction. Desmin was the dominating intermediate filament protein. The concentration of desmin and filamin increased in the hypertrophic bladders. The increased desmin-actin and filamin-actin ratios in obstructed bladders were normalized after removal of the obstruction. The results suggest that the turnover of contractile and cytoskeletal proteins is fast and can be regulated in response to changes in the functional demands in smooth muscle.
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35.
  • Malmqvist, Ulf, et al. (author)
  • Contractile properties during development of hypertrophy of the smooth muscle in the rat portal vein
  • 1988
  • In: Acta Physiologica Scandinavica. - 0001-6772. ; 133:1, s. 49-61
  • Journal article (peer-reviewed)abstract
    • Structural and mechanical alterations during hypertrophy of the rat portal vein were investigated. Growth of the vessel was induced by a partial ligature of the vessel causing an increased transmural pressure. Vessel segments from animals kept with ligature for 1, 3, 5 and 7 days, were compared with vessels from sham-operated animals. Maximal active force and vessel cross-sectional area increased with time in the ligated group. On day 7, force and cross-sectional area at the optimal length, were markedly increased in the ligated group (21.1 +/- 1.0 mN, 0.55 +/- 0.04 mm2, n = 9) compared with the control vessels (11.7 +/- 1.0 mN, 0.30 +/- 0.02 mm2, n = 7). Light and electron microscopy of preparations fixed at optimal length showed that the amount of smooth muscle and the cross-sectional area of cell profiles were almost doubled in the ligated group on day 7, consistent with hypertrophy of the smooth muscle. The force per smooth muscle cell area was similar in the two groups (ligated: 132 +/- 15; control: 145 +/- 16 mN mm-2, n = 4-5). The maximal shortening velocity was significantly lower in the hypertrophied group (ligated: 0.28 +/- 0.02; control: 0.41 +/- 0.01 optimal length s-1, n = 6). In chemically skinned preparations, activated by maximal thiophosphorylation of the myosin light chains, force was higher in the ligated group compared to the controls but no difference in maximal shortening velocity was observed. In conclusion, the increased transmural pressure is associated with a rapid increase in the amount of smooth muscle in the portal vein. The mechanical data show that after 7 days the force generating ability of the contractile system has increased in proportion to the smooth muscle cell mass. The unaltered maximal shortening velocity in the skinned hypertrophied preparations suggests that the kinetic properties of the maximally activated contractile system are unaltered. The decreased maximal shortening velocity in the intact hypertrophied preparations may reflect alterations in the excitation-contraction coupling.
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36.
  • Malmqvist, Ulf, et al. (author)
  • Correlation between isoform composition of the 17 kDa myosin light chain and maximal shortening velocity in smooth muscle
  • 1991
  • In: Pflügers Archiv. - 0031-6768. ; 418:6, s. 523-530
  • Journal article (peer-reviewed)abstract
    • The relation between the isoform distribution of the myosin 17 kDa essential light chain (LC17) and the mechanical properties of smooth muscle was investigated. The relative content of the basic (LC17b) and acidic (LC17a) isoelectric variants of the 17 kDa myosin light chain was determined in different mammalian smooth muscle tissues. The relative content of LC17b varied between muscles: rabbit rectococcygeus 0%, rabbit trachea 5%, guinea-pig taenia coli 21%, rat uterus 38%, rabbit aorta 56% and rat aorta 60%. The rate of tension development was determined following photolysis of caged-adenosine triphosphate (ATP) in skinned fibres activated with thiophosphorylation of the regulatory light chains. The half-time for force development was 0.67 s in rabbit rectococcygeus, 1.6 s in rabbit trachea, 1.13 s in guinea-pig taenia coli and 1.38 s in rabbit aorta. The maximal shortening velocity (Vmax) was determined with the isotonic quick release technique in skinned fibre preparations activated with thiophosphorylation. Vmax was 0.25 muscle lengths per second (ML/s) in rabbit rectococcygeus, 0.24 ML/s in rabbit trachea, 0.17 ML/s in guinea-pig taenia coli, 0.11 ML/s in rat uterus and 0.03 ML/s in rabbit aorta. The range of variation in Vmax between muscles was larger than in the half-time for force development. The inverse relationship between Vmax and the relative content of LC17b in the investigated muscles suggests that the type of essential myosin light chain influences the Vmax in smooth muscle.
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37.
  • Malmqvist, Ulf, et al. (author)
  • Cytoskeletal and contractile proteins in detrusor smooth muscle from bladders with outlet obstruction--a comparative study in rat and man
  • 1991
  • In: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 25:4, s. 261-267
  • Journal article (peer-reviewed)abstract
    • Detrusor biopsies were obtained from patients with urinary outlet obstruction due to prostatic enlargement and from age-matched control patients. The relative amounts of actin and myosin and their isoforms, as well as desmin and filamin were determined and compared with corresponding results from bladders from control rats and rats with 10 days of experimental outlet obstruction of the urinary bladder. In the human control detrusor the actin/myosin ratio was similar to that in the control rat. The isoform distribution of the myosin heavy chains differed between man and rat. In the biopsies from the patients with outlet obstruction and in the obstructed rat bladders the actin/myosin ratio was increased. A change in the myosin heavy chain distribution in the obstructed bladders was observed for both species. The filamin/actin ratio increased significantly in the obstructed rat bladders and tended to increase in the obstructed human bladders. Desmin was the dominating intermediate filament protein. The desmin/actin ratio increased in obstructed bladders in man and in rat.
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38.
  • Malmqvist, Ulf (author)
  • Effects of long-term portal hypertension on structure, active force and content of contractile and structural proteins in smooth muscle of the rat portal vein
  • 1994
  • In: Acta Physiologica Scandinavica. - 0001-6772. ; 150:2, s. 171-179
  • Journal article (peer-reviewed)abstract
    • Growth of the smooth muscle cells in the rat portal vein was induced by a partial ligation of the vessel. The ligation caused an increase in the transmural pressure and segments of the portal vein were investigated 6 weeks after the ligation. The spontaneous contractile activity of the ligated veins was similar to that of the control veins. In the ligated vessels the active force at optimal length for force development was doubled, 22.8 +/- 1.3 compared with 12.5 +/- 1.4 mN for the controls. The cross-sectional area of the media in the ligated veins, determined on transverse sections, increased from the control value of 0.10 +/- 0.01 to 0.19 +/- 0.01 mm2. Electron microscopy revealed that the mean cross-sectional area of the smooth muscle cells in the ligated portal vein was doubled (controls: 6.4 +/- 0.6, hypertrophic: 13.6 +/- 1.8 microns2). This suggests hypertrophy of the smooth muscle cells in the vessel wall as the cause for the increase in cross-sectional area of the ligated veins. An increase in the number of intermediate filaments was observed in the hypertrophied smooth muscle. The relative contents of contractile (myosin and actin) and structural (desmin and vimentin) proteins were determined with SDS-polyacrylamide gel electrophoresis. The actin/myosin and vimentin/actin ratios were unaltered by hypertrophy. The hypertrophied veins showed an increase in the desmin/actin ratio (control: 0.20 +/- 0.01, hypertrophied: 0.27 +/- 0.03). The increased amounts of desmin correlates with the increased number of intermediate filaments observed by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)
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39.
  • Malmqvist, Ulf, et al. (author)
  • Female pig urethral tone is dependent on Rho guanosine triphosphatases and Rho-associated kinase.
  • 2004
  • In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 171:5, s. 1955-1958
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Circular smooth muscle of the urethra generates spontaneous myogenic tone of relevance for the maintenance of continence. We tested if Rho guanosine triphosphatases (GTPases) and Rho-associated kinase (ROK) are involved in the generation of urethral tone. MATERIALS AND METHODS: Small circular strips of female pig urethra were dissected out and mounted for recording isometric force. The effect of pharmacological agents known to modulate the activity of Rho GTPases or ROK was examined. The intracellular calcium concentration was measured using fura-2. RESULTS: Urethral tone was abolished by removing extracellular calcium or by adding the calcium antagonist felodipine. The decrease in force was closely related to a decrease in intracellular calcium concentration, indicating that tone depends on membrane associated mechanisms. Toxin B, which inactivates Rho GTPases, and Y 27632, which inhibits ROK, completely abolished tone in the female pig urethra. The latter effect occurred without any change in the intracellular calcium concentration. CONCLUSIONS: The results suggests that urethral tone depends on activity in G-protein coupled pathways and inhibition of this activity is sufficient for urethral tone relaxation. Thus, to our knowledge a new pathway in the generation of urethral tone, which might be acted on by autonomic nerves during micturition, has been identified.
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40.
  • Malmqvist, Ulf, et al. (author)
  • Isoform distribution and tissue contents of contractile and cytoskeletal proteins in hypertrophied smooth muscle from rat portal vein
  • 1990
  • In: Circulation Research. - 0009-7330. ; 66:3, s. 832-845
  • Journal article (peer-reviewed)abstract
    • Growth of the smooth muscle in the rat portal vein was initiated by an increased transmural pressure. After 7 days, the cross-sectional area of the vessel wall and the maximal active force of the longitudinal muscle layer had increased twofold. Electron microscopy showed that the cell cross-sectional area was increased, suggesting cellular hypertrophy. Increased amounts of intermediate (10 nm) filaments were observed in the hypertrophied cells. The hypertrophied vessels had decreased DNA content per unit wet weight compared with the control vessels (hypertrophied, 1.5 +/- 0.1; control, 1.9 +/- 0.1 micrograms/mg; p less than 0.01). Protein composition was studied with electrophoretic methods. Compared with control preparations the hypertrophied veins had similar myosin and actin contents per unit wet weight (myosin: hypertrophied, 4.4 +/- 0.8; control, 5.9 +/- 0.9; actin: hypertrophied 12.2 +/- 0.6; control, 11.8 +/- 1.0 mg/g). Two different forms of the myosin heavy chain were detected with 5% sodium dodecyl sulfate-polyacrylamide gels. The proportion of the lower molecular weight heavy chain relative to total heavy chain content was about 30% and similar in both preparations. The relation filamin/myosin was increased in the hypertrophied vessels. Pyrophosphate gel electrophoresis revealed two protein bands, with an increase in the slower migrating band in the hypertrophied vessels possibly reflecting an increase in filamin content in the extracts. In the control portal vein alpha-actin is the dominating isoform constituting about 55% of total actin. In hypertrophied vessels, alpha-actin decreased (by 15%) and gamma-actin increased (by 20%). The portal vein contained desmin and vimentin in a ratio of about 6:1. The hypertrophied vessels showed a marked increase in the amount of these proteins (desmin/actin: hypertrophied, 0.32; control, 0.14). In conclusion, during pressure-induced growth of the portal vein, contractile protein contents increase in proportion to the increase in weight. A change in isoforms of actin occurs but no evidence for a change in myosin isoforms was found. The structural proteins increase relative to tissue weight, possibly associated with the increased number of intermediate filaments demonstrated with electron microscopy.
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41.
  • Malmqvist, Ulf, et al. (author)
  • Kinetics of contraction in depolarized smooth muscle from guinea-pig taenia coli after photodestruction of nifedipine
  • 1999
  • In: Journal of Physiology. - 1469-7793. ; 519:1, s. 213-221
  • Journal article (peer-reviewed)abstract
    • 1. The time course and kinetics of force development following activation by opening of L-type Ca2+ channels was investigated using photodestruction of the Ca2+ channel blocker nifedipine in smooth muscle from the guinea-pig taenia coli. 2. In muscles activated using high K+ and Ca2+ and subsequently inhibited with nifedipine, photodestruction of the drug using a strong ultraviolet light flash initiated a rapid contraction. The force initiated by photodestruction of nifedipine reached near-maximal levels. This procedure eliminates diffusional delays and can thus be used to investigate the kinetics of depolarization-induced contractions. 3. The rate of force development of contractions initiated by photodestruction of nifedipine was slower than that observed in maximally thiophosphorylated skinned fibres. This suggests the rate of force development is limited by activation steps in the activation cascade prior to the force generation of the cross-bridge system. 4. The rate of force development and the plateau force were dependent on the extracellular [CaCl2] suggesting that the intracellular [Ca2+] determines the rate of phosphorylation and force development. The delay between illumination and increase in force was about 300 ms. The delay was similar at low and high extracellular [CaCl2] indicating that buffering by superficial sarcoplasmatic reticulum does not introduce a delay in force development following activation of Ca2+ channels in this muscle.
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42.
  • Malmqvist, Ulf, et al. (author)
  • Lactate dehydrogenase activity and isoform distribution in normal and hypertrophic smooth muscle tissue from the rat
  • 1991
  • In: Pflügers Archiv. - 0031-6768. ; 419:3-4, s. 230-234
  • Journal article (peer-reviewed)abstract
    • The lactate dehydrogenase (LDH) activity and isoform distribution of LDH were investigated in tissue samples from the rat portal vein, aorta and urinary bladder. In addition, samples were obtained from hypertrophic urinary bladder. The total LDH activity per unit smooth muscle volume was higher in the urinary bladder compared to that in portal vein and aorta. Five LDH isoforms, reflecting different combinations of the two polypeptide chains denoted H and M, could be separated by agarose gel electrophoresis. The aorta contained more of the H form compared to the portal vein and urinary bladder. This difference suggests that the aorta, which is a slow smooth muscle, is more adapted for aerobic metabolism than the faster muscles of portal vein and urinary bladder. In the hypertrophic urinary bladder a shift in LDH isoform pattern towards less of the H form was found, which correlates with a better maintenance of contraction in anoxia in this type of hypertrophic smooth muscle.
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43.
  • Malmqvist, Ulf, et al. (author)
  • Mechanics and Ca(2+)-sensitivity of human detrusor muscle bundles studied in vitro
  • 1991
  • In: Acta Physiologica Scandinavica. - 0001-6772. ; 143:4, s. 373-380
  • Journal article (peer-reviewed)abstract
    • Mechanical properties of isolated smooth muscle strips from human urinary bladder were investigated in vitro. Bladder tissue was obtained from tumour-free wall regions of bladders from male patients undergoing cystectomy for bladder carcinoma. In intact muscle strips, activated with high-K+ solution, half-maximal force occurred at about 0.9 mM extracellular [Ca2+]. The length-active force relation was determined and the muscle strips were fixed for light and electron microscopy at optimal length for active force (1o). The maximal active force per unit smooth muscle cross-sectional area was 208 +/- 49 mN/mm2, n = 6. Chemically skinned preparations were obtained by treatment with triton X-100. These preparations had a steep [Ca2+]-force relation in the micromolar range which was influenced by calmodulin. The skinned preparations could be maximally activated by irreversible thiophosphorylation of the regulatory light chains. The force-velocity relation was determined in the maximally activated skinned muscle at 22 degrees C at 0.51o. When the muscle was shortened by 10%, force was reduced by 35% whereas the maximal shortening velocity was little affected.
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44.
  • Malmqvist, Ulf, et al. (author)
  • Regulation of force and shortening velocity by calcium and myosin phosphorylation in chemically skinned smooth muscle
  • 1996
  • In: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768. ; 433:1-2, s. 42-48
  • Journal article (peer-reviewed)abstract
    • The phosphatase inhibitor okadaic acid (OA) was used to study the relationship between [Ca2+], rates of phosphorylation/dephosphorylation and the mechanical properties of smooth muscle fibres. Force/velocity relationships were determined with the isotonic quick release technique in chemically skinned guinea-pig taenia coli muscles at 22 degrees C. In the maximally thiophosphorylated muscle neither OA (10 microM) nor Ca2+ (increase from pCa 9.0 to pCa 4.5) influenced the force-velocity relationship. When the degree of activation was altered by varying [Ca2+] in the presence of 0.5 microM calmodulin, both force and the maximal shortening velocity (Vmax) were altered. At pCa 5.75, at which force was about 35% of the maximal at pCa 4.5, Vmax was 55% of the maximal value. When OA was introduced into fibres at pCa 6.0, force was increased from less than 5% to 100% of the maximal force obtained in pCa 4.5. The relationship between the degree of myosin light chain phosphorylation and force was similar in the two types of activation; varied [OA] at constant [Ca2+] and at varied [Ca2+]. The relation between force and Vmax when the degree of activation was altered with OA was almost identical to that obtained with varied [Ca2+]. The results show that Ca2+ and OA do not influence force or Vmax in the maximally phosphorylated state and suggest that the level of myosin light chain phosphorylation is the major factor determining Vmax. The finding that the relationship between force and Vmax was similar when activation was altered with OA and Ca2+ suggests, however, that alterations in the absolute rates of phosphorylation and dephosphorylation at a constant phosphorylation level do not influence the mechanical properties of the skinned smooth muscle fibres.
  •  
45.
  • Malmqvist, Ulf, et al. (author)
  • The effects of caldesmon extraction on mechanical properties of skinned smooth muscle fibre preparations
  • 1996
  • In: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768. ; 432:2, s. 241-247
  • Journal article (peer-reviewed)abstract
    • The role of caldesmon in the regulation of smooth muscle contraction was investigated in chemically skinned smooth muscle fibres from the guinea-pig taenia coli. A 19-kDa C-terminal fragment of caldesmon gave a minor (<5%) reduction of force in fully thiophosphorylated fibres, but reduced force by about 50% at intermediate activation levels without affecting the level of light chain phosphorylation. An extraction procedure was developed using incubation in solutions containing high Mg2+ concentrations. Protein analysis revealed a selective decrease in the amount of caldesmon in the fibres. Maximal active force per cross-sectional area was unaffected. The Ca2+ dependence of active force was shifted towards lower Ca2+ concentrations and became less steep. The effects of extraction of caldesmon could in part be reversed by incubation in a solution containing purified caldesmon. The results are consistent with the hypothesis that caldesmon in smooth muscle thin filaments inhibits force generation and plays a role in regulating cooperative attachment of cross-bridges at sub-maximal levels of activation in smooth muscle.
  •  
46.
  • Mercke Odeberg, Johanna, et al. (author)
  • UGT1A polymorphisms in a Swedish cohort and a human diversity panel, and the relation to bilirubin plasma levels in males and females
  • 2006
  • In: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 62:10, s. 829-837
  • Journal article (peer-reviewed)abstract
    • Objectives: The objective of this study was to investigate the prevalence of different polymorphisms and haplotypes associated with individual variations in pharmacokinetics and drug toxicity in the uridine-diphosphate glucuronosyl transferase (UGT) 1A gene in a Swedish cohort (248 healthy volunteers) and in 14 different ethnic groups. We also estimated UGT1A genotype-dependent glucuronidation efficiency using the endogenous substrate bilirubin as an indicator. Methods: Pyrosequencing-based genotyping assays were used to determine the different polymorphisms and haplotypes. Results: Haplotype analysis of the UGT1A1 (*1*28), UGT1A6 (*1*2), and UGT1A7(*1*2*3*4) allelic variants showed that three major haplotypes constituted 84% of the allelic variants in the cohort. We identified 15 haplotypes altogether from all groups, including previously undescribed haplotypes.Testing for the association of genotype and total bilirubin levels (nonfasting) in plasma disclosed that homozygous carriers of the TA allele, irrespective of haplotype combinations, had increased levels of bilirubin compared with noncarriers, but a gender-associated difference was observed. Conclusions: In a Swedish cohort, several genetic variants in the UGT1A gene are common, but prevalence in a population may differ because of ethnicity. A phenotype based on bilirubin levels has limitations in serving as an indicator of pharmacogenetic differences in glucuronidation due to the influence of gender. Because of possible substrate overlap regarding different UGT1A isoforms, determination of haplotypes of potential cis-acting polymorphisms in the UGT1A gene should be considered in pharmacogenetic association studies regarding drugs that undergo glucuronidation.
  •  
47.
  • Midlöv, Patrik, et al. (author)
  • PERson-centredness in hypertension management using information technology (PERHIT): a protocol for a randomised controlled trial in primary health care
  • 2020
  • In: Blood Pressure. - : TAYLOR & FRANCIS LTD. - 0803-7051 .- 1651-1999. ; 29:3, s. 149-156
  • Journal article (peer-reviewed)abstract
    • Purpose: For primary health care (PHC), hypertension is the number one diagnosis for planned health care visits. The treatment of high blood pressure (BP) and its consequences constitutes a substantial economic burden. In spite of efficient antihypertensive medications, a low percentage of patients reach a well-controlled BP. The PERson-centredness in Hypertension management using Information Technology (PERHIT) Study is a multicentre randomised controlled trial. PERHIT is designed to evaluate the effect of supporting self-management on systolic blood pressure by the use of information technology in Swedish primary health care. Materials and Methods: After inclusion, 900 patients from 36 PHC centres are randomised to two groups. In the intervention group, patients are provided with a self-management support system including a home-BP monitor and further requested to perform self-reports and measure BP every evening for eight consecutive weeks. In the control group, patients receive treatment as usual. Results: The primary outcome will be the change in systolic blood pressure in patients with hypertension. In addition, person-centredness, daily life activities, awareness of risk and health care costs will also be evaluated. Conclusion: The results of this randomised controlled trial with assessment of blood pressure and same-day self-reports will provide patients a tool to understand the interplay between blood pressure and lifestyle applicable to primary health care. The self-management support system may be of importance for improved adherence to treatment and persistence to treatment recommendations.
  •  
48.
  • Norman, Elisabeth, et al. (author)
  • Thiopental pharmacokinetics in newborn infants: a case report of overdose.
  • 2009
  • In: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 98, s. 1680-1682
  • Journal article (peer-reviewed)abstract
    • Abstract Thiopental may be used for sedation before intubation in newborn infants. A boy, born at 33 weeks of gestation (gw); birth weight 2435 g, was prescribed thiopental 3 mg/kg before intubation. He developed temporary hypotension and oxygen desaturation, and remained unconscious for longer than expected with a suppressed electroencephalography for 48 h. Serum thiopental concentration was 82, 59, 42 and 32 mumol/L after 20 min and 6, 24 and 68 h respectively. Serum concentrations from five newborn infants at the same time points after intubation with the same thiopental dose were used as reference values, and indicated a 10-fold overdose in the index case. The cause of the overdose could not be identified. The infant recovered; cerebral magnetic resonance imaging at the age of 42 gw and psychomotor development at 2 years were normal. These results show that thiopental concentrations are variable in neonates and there is a high risk of dosage error as no specific paediatric formulation is available. Conclusion: Well-designed procedures and continuous education are required to prevent errors and adverse events during drug delivery to newborn infants. To develop a safe method of administration for thiopental, an extended pharmacokinetic and pharmacodynamic study in neonates is warranted.
  •  
49.
  • Olsson, Ola, et al. (author)
  • Variability of patch type preferences in relation to resource availability and breeding success in a bird
  • 2001
  • In: Oecologia. - : Springer Science and Business Media LLC. - 1432-1939 .- 0029-8549. ; 127:3, s. 435-443
  • Journal article (peer-reviewed)abstract
    • This paper investigates how variability in partial foraging preferences for patch types can be used as a behavioral indicator of the energetic value of that patch type, and of overall food availability in the territory. The species studied was the lesser spotted woodpecker (Dendrocopos minor) and the patch types it uses are four groups of tree species (oak Quercus robur, birch Betula pendula, B. pubescens, alder Alnus glutinosa, and lime Tilia cordata), in which it feeds upon wood-living insect larvae. We partition the variation in foraging preferences into three scales. Firstly, within territories, the foraging preference for a tree species group was positively related to the prey density in that species group. That is, the preferences measure the patch types' energetic profit-abilities. This result should be general in cases like the present, where the costs of using different alternatives do not differ substantially. It may therefore be the preferred behavioral indicator in determining the relative benefits associated with different alternatives. Secondly, between the seven years of study, much of the variation in tree species group preferences was attributable to measured fluctuations in the density of one important prey species (Argyresthia goedarthella, Argyresthidae, Lepidoptera), which occurred in some years on birch, in others on alder, and in one year was virtually absent. Thus, in concordance with the previous result, the values of these tree species groups fluctuated between years according to prey density. Thirdly, between territories, we found that the preference for one tree species, lime, was higher in areas where it was more abundant. We attribute this to the fact that the density (per patch) of at least one important prey species (Stenostola dubia, Cerambycidae, Coleoptera) on lime increased with the abundance of its host tree species in the territory. That is, the overall food availability was higher in territories where lime was more common. Hence, the preference for lime estimates overall food availability. This conclusion is strengthened by two additional facts: the preference for lime correlates positively (1) with the average giving-up density of food, which has previously been shown to estimate overall food availability in the territories, and (2) with reproductive success, at least during the early stages of reproduction.
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50.
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