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1.
  • Elhai, M, et al. (författare)
  • Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
  • 2019
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
  • Tidskriftsartikel (refereegranskat)abstract
    • To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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  • Sjoqvist, S, et al. (författare)
  • Publisher Correction: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
  • 2018
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 16208-
  • Tidskriftsartikel (refereegranskat)abstract
    • Nature Communications 5: Article number: 3562 (2014); Published online: 15 April 2014; Updated: 10 April 2018 The original HTML version of this Article had an incorrect article number of 4562; it should have been 3562. This has now been corrected in the HTML; the PDF version of the Article was correct from the time of publication.
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  • Sjoqvist, S, et al. (författare)
  • Retraction: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
  • 2017
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15077-
  • Tidskriftsartikel (refereegranskat)abstract
    • Nature Communications 5: Article number: 3562 (2014); Published 15 April 2014; Updated 21 March 2017 This Article is retracted by the authors. Nature Communications previously issued an Editorial Expression of Concern (http://www.nature.com/articles/ncomms13310) related to this Article, following the publication of a report commissioned by The Karolinska Institute and prepared by the Expert Group for Misconduct in Research at the Swedish Central Ethical Review Board.
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  • Becker, M, et al. (författare)
  • Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis
  • 2019
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:9, s. 1242-1248
  • Tidskriftsartikel (refereegranskat)abstract
    • Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database.MethodsInclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression.ResultsOf 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model.ConclusionsThe use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials.
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  • Berman, Anne H., et al. (författare)
  • Children's Quality of Life Based on the KIDSCREEN-27 : Child Self-Report, Parent Ratings and Child-Parent Agreement in a Swedish Random Population Sample
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The KIDSCREEN-27 is a measure of child and adolescent quality of life (QoL), with excellent psychometric properties, available in child-report and parent-rating versions in 38 languages. This study provides child-reported and parent-rated norms for the KIDSCREEN-27 among Swedish 11-16 year-olds, as well as child-parent agreement. Sociodemographic correlates of self-reported wellbeing and parent-rated wellbeing were also measured. Methods A random population sample consisting of 600 children aged 11-16, 100 per age group and one of their parents (N = 1200), were approached for response to self-reported and parentrated versions of the KIDSCREEN-27. Parents were also asked about their education, employment status and their own QoL based on the 26-item WHOQOL-Bref. Based on the final sampling pool of 1158 persons, a 34.8% response rate of 403 individuals was obtained, including 175 child-parent pairs, 27 child singleton responders and 26 parent singletons. Gender and age differences for parent ratings and child-reported data were analyzed using t-tests and the Mann-Whitney U-test. Post-hoc Dunn tests were conducted for pairwise comparisons when the p-value for specific subscales was 0.05 or lower. Child-parent agreement was tested item-by-item, using the Prevalence-and Bias-Adjusted Kappa (PABAK) coefficient for ordinal data (PABAK-OS); dimensional and total score agreement was evaluated based on dichotomous cut-offs for lower well-being, using the PABAK and total, continuous scores were evaluated using Bland-Altman plots. Results Compared to European norms, Swedish children in this sample scored lower on Physical wellbeing (48.8 SE/49.94 EU) but higher on the other KIDSCREEN-27 dimensions: Psychological wellbeing (53.4/49.77), Parent relations and autonomy (55.1/49.99), Social Support and peers (54.1/49.94) and School (55.8/50.01). Older children self-reported lower wellbeing than younger children. No significant self-reported gender differences occurred and parent ratings showed no gender or age differences. Item-by-item child-parent agreement was slight for 14 items (51.9%), fair for 12 items (44.4%), and less than chance for one item (3.7%), but agreement on all dimensions as well as the total score was substantial according to the PABAK-OS. Visual interpretation of the Bland-Altman plot suggested that when children's average wellbeing score was lower parents seemed to rate their children as having relatively higher total wellbeing, but as children's average wellbeing score increased, parents tended to rate their children as having relatively lower total wellbeing. Children living with both parents had higher wellbeing than those who lived with only one parent. Conclusions Results agreed with European findings that adolescent wellbeing decreases with age but contrasted with some prior Swedish research identifying better wellbeing for boys on all dimensions but Social support and peers. The study suggests the importance of considering children's own reports and not only parental or other informant ratings. Future research should be conducted at regular intervals and encompass larger samples.
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  • Berman, Anne H., et al. (författare)
  • Children’s Quality of Life Based on the KIDSCREEN-27
  • 2016
  • Ingår i: PLoS ONE. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    •  Background:  The KIDSCREEN-27 is a measure of child and adolescent quality of life (QoL), with excellent psychometric properties, available in child-report and parent-rating versions in 38 languages. This study provides child-reported and parent-rated norms for the KIDSCREEN-27 among Swedish 11-16 year-olds, as well as child-parent agreement. Sociodemographic correlates of self-reported wellbeing and parent-rated wellbeing were also measured. Methods:  A random population sample consisting of 600 children aged 11-16, 100 per age group and one of their parents (N = 1200), were approached for response to self-reported and parent-rated versions of the KIDSCREEN-27. Parents were also asked about their education, employment status and their own QoL based on the 26-item WHOQOL-Bref. Based on the final sampling pool of 1158 persons, a 34.8% response rate of 403 individuals was obtained, including 175 child-parent pairs, 27 child singleton responders and 26 parent singletons. Gender and age differences for parent ratings and child-reported data were analyzed using t-tests and the Mann-Whitney U-test. Post-hoc Dunn tests were conducted for pairwise comparisons when the p-value for specific subscales was 0.05 or lower. Child-parent agreement was tested item-by-item, using the Prevalence- and Bias-Adjusted Kappa (PABAK) coefficient for ordinal data (PABAK-OS); dimensional and total score agreement was evaluated based on dichotomous cut-offs for lower well-being, using the PABAK and total, continuous scores were evaluated using Bland-Altman plots. Results:  Compared to European norms, Swedish children in this sample scored lower on Physical wellbeing (48.8 SE/49.94 EU) but higher on the other KIDSCREEN-27 dimensions: Psychological wellbeing (53.4/49.77), Parent relations and autonomy (55.1/49.99), Social Support and peers (54.1/49.94) and School (55.8/50.01). Older children self-reported lower wellbeing than younger children. No significant self-reported gender differences occurred and parent ratings showed no gender or age differences. Item-by-item child-parent agreement was slight for 14 items (51.9%), fair for 12 items (44.4%), and less than chance for one item (3.7%), but agreement on all dimensions as well as the total score was substantial according to the PABAK-OS. Visual interpretation of the Bland-Altman plot suggested that when children's average wellbeing score was lower parents seemed to rate their children as having relatively higher total wellbeing, but as children's average wellbeing score increased, parents tended to rate their children as having relatively lower total wellbeing. Children living with both parents had higher wellbeing than those who lived with only one parent. Conclusions:  Results agreed with European findings that adolescent wellbeing decreases with age but contrasted with some prior Swedish research identifying better wellbeing for boys on all dimensions but Social support and peers. The study suggests the importance of considering children's own reports and not only parental or other informant ratings. Future research should be conducted at regular intervals and encompass larger samples.
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  • Elhai, Muriel, et al. (författare)
  • Mapping and predicting mortality from systemic sclerosis
  • 2017
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:11, s. 1897-1905
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc). Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival.
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  • Fransen, J., et al. (författare)
  • Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres
  • 2011
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:10, s. 1788-1792
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate in other patients, especially from other centres or countries. A study was undertaken to validate the prognostic model to predict 5-year survival in SSc in other centres throughout Europe. Methods A European multicentre cohort of patients with SSc diagnosed before 2002 was established. Patients with SSc according to the preliminary American College of Rheumatology classification criteria were eligible for the study when they were followed for at least 5 years or shorter if they died. The primary outcome was 5-year survival after diagnosis of SSc. The predefined prognostic model uses the following baseline variables: age, gender, presence of urine protein, erythrocyte sedimentation rate (ESR) and carbon monoxide diffusing capacity (DLCO). Results Data were available for 1049 patients, 119 (11%) of whom died within 5 years after diagnosis. Of the patients, 85% were female, the mean (SD) age at diagnosis was 50 (14) years and 30% were classified as having diffuse cutaneous SSc. The prognostic model with age (OR 1.03), male gender (OR 1.93), urine protein (OR 2.29), elevated ESR (1.89) and low DLCO (OR 1.94) had an area under the receiver operating characteristic curve of 0.78. Death occurred in 12 (2.2%) of 509 patients with no risk factors, 45 (13%) of 349 patients with one risk factor, 55 (33%) of 168 patients with two risk factors and 7 (30%) of 23 patients with three risk factors. Conclusion A simple prognostic model using three disease factors to predict 5-year survival at diagnosis in SSc showed reasonable performance upon validation in a European multicentre study.
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  • Gallagher, Bernard, et al. (författare)
  • National Human Research Ethics : A Preliminary Comparative Case Study of Germany, Great Britain, Romania, and Sweden
  • 2016
  • Ingår i: Ethics & Behavior. - : Informa UK Limited. - 1050-8422 .- 1532-7019. ; 26:7, s. 586-606
  • Tidskriftsartikel (refereegranskat)abstract
    • Although international research is increasing in volume and importance, there remains a dearth of knowledge on similarities and differences in “national human research ethics” (NHREs), that is, national ethical guidelines (NEGs), Institutional Review Boards (IRBs), and research stakeholder’ ethical attitudes and behaviors (EABs). We begin to address this situation by reporting upon our experiences in conducting a multinational study into the mental health of children who had a parent/carer in prison. The study was conducted in 4 countries: Germany, Great Britain, Romania, and Sweden. Data on NHREs were gathered via a questionnaire survey, two ethics-related seminars, and ongoing contact between members of the research consortium. There was correspondence but even more so divergence between countries in the availability of NEGs and IRBs and in researcher’ EABs. Differences in NHREs have implications particularly in terms of harmonization but also for ethical philosophy and practice and for research integrity.
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  • Hedenius, Martina, 1970-, et al. (författare)
  • Impaired implicit sequence learning in children with developmental dyslexia
  • 2013
  • Ingår i: Research in Developmental Disabilities. - : Elsevier. - 0891-4222 .- 1873-3379. ; 34:11, s. 3924-3935
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been proposed that an impairment of procedural memory underlies a range of linguistic, cognitive and motor impairments observed in developmental dyslexia (DD). However, studies designed to test this hypothesis using the implicit sequence learning paradigm have yielded inconsistent results. A fundamental aspect of procedural learning is that it takes place over an extended time-period that may be divided into distinct stages based on both behavioural characteristics and neural correlates of performance. Yet, no study of implicit sequence learning in children with DD has included learning stages beyond a single practice session. The present study was designed to fill this important gap by extending the investigation to include the effects of overnight consolidation as well as those of further practice on a subsequent day. The results suggest that the most pronounced procedural learning impairment in DD may emerge only after extended practice, in learning stages beyond a single practice session.
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  • Hjelmqvist, H, et al. (författare)
  • Increased resistance to haemorrhage induced by intracerebroventricular infusion of hypertonic NaCl in conscious sheep.
  • 1992
  • Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 145:2, s. 177-86
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of elevated cerebrospinal fluid Na+ concentration (CSF [Na+]) on the tolerance of blood loss, and concomitant cardiovascular and humoral responses were studied in conscious sheep. A slow (0.7 ml kg-1 min-1) venous haemorrhage was continued until the mean systemic arterial pressure suddenly decreased to less than 50 mmHg, or in the absence of hypotension, until a total blood loss of 25 ml kg-1. Significantly more blood had to be removed to induce hypotension in animals receiving an intracerebroventricular (i.c.v.) infusion (0.02 ml min-1) of 0.5 M NaCl (starting 30 min before haemorrhage and continued throughout the experiment) compared to control haemorrhages without concomitant i.c.v. infusion (22.7 +/- 1.2 ml vs 16.9 +/- 0.9 ml kg-1). In one animal, subjected to 0.5 M NaCl infusion, the blood pressure was still maintained at 25 ml kg-1 of haemorrhage. In spite of a larger blood loss, animals receiving i.c.v. infusion of hypertonic NaCl had an improved recovery of the blood pressure after haemorrhage, due to a better maintained cardiac output rather than to a reinforced increase of the vascular resistance. The improved cardiovascular responses to haemorrhage during elevated CSF [Na+] are not readily explained by the effects on the plasma concentrations of vasopressin, angiotensin II or noradrenaline, although the latter was augmented. The plasma protein concentration decreased already during the 30 min of hypertonic NaCl infusion preceding haemorrhage, and the haemodilution caused by the subsequent blood removal was aggravated, which indicates that this treatment also causes transfer of fluid to the plasma compartment. We conclude that elevated CSF [Na+] increases tolerance to haemorrhage and improves cardiovascular function after blood loss in sheep. Since the haemodynamic responses in many respects were similar to those reported in response to the systemic administration of a small volume of hypertonic NaCl solution in haemorrhagic shock, part of the effect of that treatment may be mediated via cerebral effects of increased Na+ concentration.
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  • Liu, Bojing, et al. (författare)
  • Child self-report and parent ratings for the Strengths and Difficulties Questionnaire : Norms and agreement in a Swedish random population sample
  • 2017
  • Ingår i: Scandinavian Journal of Child and Adolescent Psychiatry and Psychology. - : Walter de Gruyter GmbH. - 2245-8875. ; 5:1, s. 13-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Strengths and Difficulties Questionnaire (SDQ) measures behavioral problems among children and adolescents. Prior research in Sweden has included child self-report or parent ratings from community or population data. Objective: To provide child-reported and parent-rated SDQ norms for 11- to 16-year-olds, as well as data on child-parent agreement and parental sociodemographic correlates: education, employment status, and quality of life. Method: A random population sample with 600 children aged 11 to 16 years, 100 per age group, and one of their parents (N=1200) yielded a sampling pool of 1158 participants and a 34.8 % response rate, including 175 child-parent pairs and 27 and 26 child/parent singletons. Responses to child and parent versions of the extended SDQ were analyzed by child gender and age. Child-parent agreement was evaluated using the Prevalence- and Bias-Adjusted Kappa and Bland-Altman plots. Results: Older children reported greater difficulties compared with younger children, while girls reported a higher negative impact of difficulties on daily life in comparison to boys. Child-parent item-by-item agreement was fair to slight on 15 of the 25 SDQ items, perfect to moderate on 9 items, and less than chance on 1 item, but generally high regarding dichotomous assignment to the "raised difficulties" or "normal" groups, based on subscales and the total SDQ score. Greater difficulties for children were reported by parents born outside Sweden, parents of children born outside Sweden, parents lacking regular employment, and parents with lower education or lower quality of life. In relation to other child-parent pairs, parents born outside Sweden perceived greater difficulties for their children compared with the children's own ratings. Parents with better physical health and social relationships rated their children as having fewer difficulties compared with the rates reported by children. Conclusions: Gender differences contrasted with prior Swedish studies showing higher ratings for boys on hyperactivity and total difficulties and for girls on emotional symptoms. However, findings on increased difficulties with age concurred with prior studies. Research on children's mental health should be widely and systematically conducted at regular intervals and encompasses large, representative samples in order to inform national public health and health-care policy regarding measures to support children and enhance their mental health.
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  • Liu, Bojing, et al. (författare)
  • Child self-report and parent ratings for the Strengths and Difficulties Questionnaire
  • 2017
  • Ingår i: Scandinavian Journal of Child and Adolescent Psychiatry and Psychology. - : Walter de Gruyter GmbH. - 2245-8875. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:The Strengths and Difficulties Questionnaire (SDQ) measures behavioral problems among children and adolescents. Prior research in Sweden has included child self-report or parent ratings from community or population data.Objective:To provide child-reported and parent-rated SDQ norms for 11- to 16-year-olds, as well as data on child–parent agreement and parental sociodemographic correlates: education, employment status, and quality of life.Method:A random population sample with 600 children aged 11 to 16 years, 100 per age group, and one of their parents (N=1200) yielded a sampling pool of 1158 participants and a 34.8% response rate, including 175 child–parent pairs and 27 and 26 child/parent singletons. Responses to child and parent versions of the extended SDQ were analyzed by child gender and age. Child–parent agreement was evaluated using the Prevalence- and Bias-Adjusted Kappa and Bland–Altman plots.Results:Older children reported greater difficulties compared with younger children, while girls reported a higher negative impact of difficulties on daily life in comparison to boys. Child–parent item-by-item agreement was fair to slight on 15 of the 25 SDQ items, perfect to moderate on 9 items, and less than chance on 1 item, but generally high regarding dichotomous assignment to the “raised difficulties” or “normal” groups, based on subscales and the total SDQ score. Greater difficulties for children were reported by parents born outside Sweden, parents of children born outside Sweden, parents lacking regular employment, and parents with lower education or lower quality of life. In relation to other child–parent pairs, parents born outside Sweden perceived greater difficulties for their children compared with the children’s own ratings. Parents with better physical health and social relationships rated their children as having fewer difficulties compared with the rates reported by children.Conclusions:Gender differences contrasted with prior Swedish studies showing higher ratings for boys on hyperactivity and total difficulties and for girls on emotional symptoms. However, findings on increased difficulties with age concurred with prior studies. Research on children’s mental health should be widely and systematically conducted at regular intervals and encompasses large, representative samples in order to inform national public health and health-care policy regarding measures to support children and enhance their mental health.Graphical ABSTRACT  
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  • Ullman, B, et al. (författare)
  • Cardiovascular effects and cardiopulmonary plasma gradients following intravenous infusion of neuropeptide Y in humans: negative dromotropic effect on atrioventricular node conduction
  • 2002
  • Ingår i: Clinical science (London, England : 1979). - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 103:6, s. 535-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuropeptide Y (NPY) is co-released with noradrenaline from sympathetic nerves, has a strong vasoconstrictive action, and causes an attenuation of parasympathetic action in animal experiments. The plasma level of NPY is greatly elevated in patients with congestive heart failure, but the clinical relevance of this finding is unclear. Central haemodynamic effects, cardiac conduction system electrophysiology and coronary sinus blood flow were therefore studied in two sets of experiments, each carried out on seven healthy men. In the first series, NPY was given intravenously at doses of 3, 10 and 30pmolμmin-1μkg-1, and in the second it was given as a bolus injection of 90, 200 or 900pmol/kg, which resulted in plasma concentrations similar to those seen in heart failure patients. During continuous infusion of NPY, systemic blood pressure increased slightly, but myocardial perfusion, cardiac output, pulmonary arterial pressure, cardiac conduction intervals and atrioventricular (AV) node functional measures remained unchanged. In contrast, the bolus injection of NPY evoked prolongation and block (in four out of seven subjects) of AV node conduction, but did not affect haemodynamic variables, apart from a minor increase in systemic blood pressure. Impaired AV node conduction is a novel observation, which might reflect a baroreceptor-mediated vagal reflex, or–more likely–an NPY-induced direct negative dromotropic effect, caused by a reduction of the L-type calcium current as observed in vitro, or a combination of the two.
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