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  • 151.
    Ahmed, Adan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bemötande av barn på röntgen2016Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Barnen är oftast rädda och oroliga då de kommer till en röntgenundersökning på grund av att det är en främmande miljö utrustad med högteknologisk apparatur som är skrämmande för barnet. För att bemöta dessa barn behöver röntgensjuksköterskan ha kunskap och färdigheter om bemötande av barn. Ett bra samspel mellan röntgensjuksköterskan och barnen som bygger på ömsesidig tillit och respekt ger trygghet hos barnet och det kan samarbeta bättre under röntgenundersökningen. På en kort tid, ofta mindre än 5 minuter, måste en röntgensjuksköterska överföra viktig information om undersökningen till barnet. Därför är det viktigt för röntgensjuksköterskan att ha kunskap om gott bemötande av barn.

  • 152.
    Ahnesjö, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    van Veelen, Bob
    Elekta Brachytherapy, NL-3905 TH Veenendaal, Netherlands..
    Tedgren, Asa Carlsson
    Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci IMH, Radiat Phys, SE-58185 Linkoping, Sweden.;Karolinska Univ Hosp, Dept Med Phys, Sect Radiotherapy Phys & Engn, SE-17176 Stockholm, Sweden..
    Collapsed cone dose calculations for heterogeneous tissues in brachytherapy using primary and scatter separation source data2017In: Computer Methods and Programs in Biomedicine, ISSN 0169-2607, E-ISSN 1872-7565, Vol. 139, p. 17-29Article in journal (Refereed)
    Abstract [en]

    Background and Objective: Brachytherapy is a form of radiation therapy using sealed radiation sources inserted within or in the vicinity of the tumor of, e.g., gynecological, prostate or head and neck cancers. Accurate dose calculation is a crucial part of the treatment planning. Several reviews have called for clinical software with model-based algorithms that better take into account the effects of patient individual distribution of tissues, source-channel and shielding attenuation than the commonly employed TG-43 formalism which simply map homogeneous water dose distributions onto the patient. In this paper we give a comprehensive and thorough derivation of such an algorithm based on collapsed cone point-kernel superposition, and describe details of its implementation into a commercial treatment planning system for clinical use. Methods: A brachytherapy version of the collapsed-cone algorithm using analytical raytraces of the primary photon radiation followed by successive scattering dose calculation for once and multiply scattered photons is described in detail, including derivation of the corresponding set of recursive equations for energy transport along cone axes/transport lines and the coupling to clinical source modeling. Specific implementation issues for setting up of the calculation grid, handling of intravoxel gradients and voxels partly containing non patient applicator material are given. Results: Sample runs for two clinical cases are shown, one being a gynecological application with a tungsten-shielded applicator and one a breast implant. These two cases demonstrate the impact of improved dose calculation versus TG-43 formalism. Conclusions: Use of model-based dose calculation algorithms for brachytherapy taking the three-dimensional treatment geometry into account increases the dosimetric accuracy in planning and follow up of treatments. The comprehensive description and derivations provided gives a rigid background for further clinical, educational and research applications.

  • 153. Aho, Leena
    et al.
    Jolkkonen, Jukka
    Alafuzoff, Irina
    Kuopio University, Finland.
    Beta-amyloid aggregation in human brains with cerebrovascular lesions.2006In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 37, no 12, p. 2940-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The present study assessed beta-amyloid (Abeta) protein aggregates in postmortem human brains in subjects who had experienced stroke to examine the proposed association between ischemic stress and the accumulation of Abeta reported in rodents.

    METHODS: A sample of 484 postmortem brains from nondemented subjects, lacking isocortical neurodegenerative pathology with verified cerebrovascular lesions, and 57 age-matched controls were assessed with respect to Abeta, Abeta40, and Abeta42 aggregates in the cortex and thalamus by immunohistochemical techniques.

    RESULTS: The load of Abeta aggregates did not display a significant association with cerebrovascular lesions. The load of Abeta, Abeta40, and Abeta42 aggregates increased with age, and there was a tendency toward higher odds ratios for Abeta aggregates, though not statistically significant, in subjects with acute cerebrovascular lesions. In the oldest subjects with cerebrovascular lesions and with both thalamic and cortical Abeta aggregates, the load of thalamic Abeta42 was significantly higher than the load of Abeta40.

    CONCLUSIONS: Our findings indicate that cerebrovascular disease does not influence the load of Abeta, whereas a shift of aggregation from the Abeta40 to the Abeta42 residue is noted in the thalamus but only in aged subjects. It is impossible, however, to state whether this result is attributable to increased Abeta production, its insufficient elimination, or other susceptibility factors.

  • 154. Aho, Leena
    et al.
    Karkola, Kari
    Juusela, Jari
    Alafuzoff, Irina
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Heavy alcohol consumption and neuropathological lesions: a post-mortem human study2009In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 87, no 12, p. 2786-2792Article in journal (Refereed)
    Abstract [en]

    Epidemiological studies have indicated that excessive alcohol consumption leads to cognitive impairment, but the specific pathological mechanism involved remains unknown. The present study evaluated the association between heavy alcohol intake and the neuropathological hallmark lesions of the three most common neurodegenerative disorders, i.e., Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and vascular cognitive impairment (VCI), in post-mortem human brains. The study cohort was sampled from the subjects who underwent a medicolegal autopsy during a 6-month period in 1999 and it included 54 heavy alcohol consumers and 54 age- and gender-matched control subjects. Immunohistochemical methodology was used to visualize the aggregation of beta-amyloid, hyperphosphorylated tau, and alpha-synuclein and the extent of infarcts. In the present study, no statistically significant influence was observed for alcohol consumption on the extent of neuropathological lesions encountered in the three most common degenerative disorders. Our results indicate that alcohol-related dementia differs from VCI, AD, and DLB; i.e., it has a different etiology and pathogenesis.

  • 155. Aho, Leena
    et al.
    Parkkinen, Laura
    Pirttila, Tuula
    Alafuzoff, Irina
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Systematic appraisal using immunohistochemistry of brain pathology in aged and demented subjects.2008In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 25, no 5, p. 423-32Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Abnormal processing of hyperphosphorylated tau (HPtau), amyloid-beta (Abeta) and alpha-synuclein (alphaS) proteins is considered as causative with regard to the clinical symptoms in age-related neurodegenerative diseases.

    METHODS: In this retrospective, postmortem study applying immunohistochemical methodology, we assessed Alzheimer's-disease (AD)-related HPtau and Abeta pathology in 178 subjects with alphaS pathology.

    RESULTS: These pathologies were frequently seen concomitantly, i.e. HPtau in 83% and Abeta in 62% of the alphaS-positive cases. Furthermore, the striatum was frequently involved, particularly in subjects with cognitive impairment (65%). The predictive value of widespread HPtau pathology, i.e. stages V-VI, with respect to cognitive impairment was high, since all 18 subjects presenting with this stage were demented. In contrast, the predictive value of widespread alphaS pathology, i.e. stages 5-6 according to Braak's Parkinson disease staging, was debatable. Fifty-three percent of the subjects with widespread alphaS pathology and no or mild AD-related HPtau pathology were cognitively unimpaired. It is noteworthy that striatal Abeta pathology was more often seen in demented subjects independently of HPtau and/or alphaS status.

    CONCLUSION: The causative pathology in subjects with clinically diagnosed dementia with Lewy bodies needs to be clarified in future studies.

  • 156. Aho, Leena
    et al.
    Pikkarainen, Maria
    Hiltunen, Mikko
    Leinonen, Ville
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Immunohistochemical Visualization of Amyloid-β Protein Precursor and Amyloid-β in Extra- and Intracellular Compartments in the Human Brain2010In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 20, no 4, p. 1015-1028Article in journal (Refereed)
    Abstract [en]

    Amyloid-beta (Abeta) peptide, a cleavage product of the amyloid-beta protein precursor (AbetaPP), has been reported to be detected in the intracellular compartment. Most studies reporting the presence of intracellular Abeta are based on the use of immunohistochemistry. In this study, the presence of AbetaPP and Abeta was assessed by applying immunohistochemistry in postmortem human brain tissue samples obtained from 10 neurologically intact subjects, the youngest being 2 years of age, one aged with mild cognitive impairment, 14 neurologically diseased, and in one brain biopsy sample obtained from a subject with normal pressure hydrocephalus. Intracellular immunoreactivity was detected in all ages independent of the disease state or existence of extracellular Abeta aggregates with all antibodies directed to AbetaPP, with three Abeta antibodies (4G8, 6E10, and 82E1), clones that are unable to distinguish Abeta from AbetaPP. These results suggest that it is AbetaPP rather than Abeta that is detected intracellularly when using the antibodies listed above. Furthermore, the staining results varied when different pretreatment strategies were applied. Interestingly intracellular Abeta was detected with antibodies directed to the C-terminus of Abeta (neoepitope) in subjects with Alzheimer's disease. The lack of intracellular immunoreactivity in unimpaired subjects, when using antibodies against neoepitopes, may be due to a lack or a low level of the protein that is thus undetectable at light microscopic level by immunohistochemistry method. The staining results and conclusions depended strongly on the chosen antibody and the pretreatment strategy and thus multiple antibodies must be used when assessing the intracellular accumulation of Abeta.

  • 157.
    Aila Gustafsson, Sanna
    et al.
    Örebro universitet.
    Edlund, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Kjellin, Lars
    Örebro universitet.
    Norring, Claes
    Karolinska institutet, Stockholm.
    Characteristics measured by the Eating Disorder Inventory for children at risk and protective factors for disordered eating in adolescent girls2010In: International Journal of Women´s Health, ISSN 1179-1411, Vol. 2, p. 375-379Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to examine longitudinally the role of characteristics measured by the Eating Disorder Inventory-Child version (EDI-C) to find early predictors that might constitute risk and protective factors in the development of disordered eating.

    Method: Participants were divided into three groups based on eating attitudes at T2: disordered eating (n = 49), intermediate eating concern (n = 260), and healthy eating attitudes (n = 120). EDI-C from T1 (four to five years earlier) was then analyzed to find predictors of group classification at T2.

    Results: Drive for thinness and body dissatisfaction emerged as risk factors at T1, while drive for thinness, body dissatisfaction, and interoceptive awareness emerged as protective factors after controlling for initial eating concerns and body mass index.

    Discussion: Eating disorders should not be seen as a result of a premorbid personality type. Rather we should take a more social-psychological perspective to explain how individual and sociocultural factors work together in the development of these conditions.

  • 158. Aila Gustafsson, Sanna
    et al.
    Edlund, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Kjellin, Lars
    Norring, Claes
    Risk and protective factors for disturbed eating in adolescent girls: aspects of perfectionism and attitudes to eating and weight2009In: European eating disorders review, ISSN 1072-4133, E-ISSN 1099-0968, Vol. 17, no 5, p. 380-389Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to longitudinally examine the role of personal standards, self-evaluation, perceived benefits of thinness and attitudes to eating and weight in the development of healthy versus disturbed eating in adolescent girls. In a longitudinal study, girls who participated in two assessments, four to five years apart, were divided into three groups according to the attitudes to eating that they manifested at the second evaluation: those with disturbed eating patterns (DE-group, n = 49), those with intermediate concerns about eating (IE-group, n = 260) and those with healthy eating attitudes (HE-group, n = 120). Variables concerning attitudes to eating and weight and physical self-evaluation emerged as risk factors, whereas personal standards or self-evaluation in general did not. Protective factors were a low BMI, healthy eating attitudes, an accepting attitude towards body size and a positive self-evaluation, particularly with regard to physical and psychological characteristics. The results of this study contribute to the understanding of early risk and protective factors for eating disturbances in girls.

  • 159.
    Aimo, Alberto
    et al.
    Scuola Super Sant Anna, Pisa, Italy.
    Januzzi, James L
    Massachusetts Gen Hosp, Boston, MA, USA; Harvard Clin Res Inst, Boston, MA USA.
    Vergaro, Giuseppe
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Ripoli, Andrea
    Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Latini, Roberto
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Masson, Serge
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Magnoli, Michela
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Anand, Inder S
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN, USA; VA Med Ctr, Dept Cardiol, Minneapolis, MN USA.
    Cohn, Jay N
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN, USA.
    Tavazzi, Luigi
    ES Hlth Sci Fdn, GVM Hosp Care & Res, Cotignola, Italy.
    Tognoni, Gianni
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Gravning, Jørgen
    Oslo Univ Hosp, Dept Cardiol, Ulleval, Norway; Univ Oslo, Ctr Heart Failure Res, Oslo, Norway.
    Ueland, Thor
    Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, Oslo, Norway; Univ Oslo, Fac Med, Oslo, Norway; Univ Tromso, Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway.
    Nymo, Ståle H
    Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, Oslo, Norway.
    Brunner-La Rocca, Hans-Peter
    Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherlands.
    Bayes-Genis, Antoni
    Hosp Badalona Germans Trias & Pujol, Badalona, Barcelona, Spain.
    Lupón, Josep
    Hosp Badalona Germans Trias & Pujol, Badalona, Barcelona, Spain.
    de Boer, Rudolf A
    Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
    Yoshihisa, Akiomi
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Takeishi, Yasuchika
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Egstrup, Michael
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Gustafsson, Ida
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Gaggin, Hanna K
    Massachusetts Gen Hosp, Boston, MA, USA; Harvard Clin Res Inst, Boston, MA, USA.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Huber, Kurt
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Tentzeris, Ioannis
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Tang, Wai H.W.
    Cleveland Clin, Inst Heart & Vasc, Cleveland, OH, USA.
    Grodin, Justin
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX USA.
    Passino, Claudio
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Emdin, Michele
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An Individual Patient Data Meta-Analysis2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, no 3, p. 286-297Article in journal (Refereed)
    Abstract [en]

    Background: Most patients with chronic heart failure have detectable troponin concentrations when evaluated by high-sensitivity assays. The prognostic relevance of this finding has not been clearly established so far. We aimed to assess high-sensitivity troponin assay for risk stratification in chronic heart failure through a meta-analysis approach.

    Methods: Medline, EMBASE, Cochrane Library, and Scopus were searched in April 2017 by 2 independent authors. The terms were “troponin” AND “heart failure” OR “cardiac failure” OR “cardiac dysfunction” OR “cardiac insufficiency” OR “left ventricular dysfunction.” Inclusion criteria were English language, clinical stability, use of a high-sensitivity troponin assay, follow-up studies, and availability of individual patient data after request to authors. Data retrieved from articles and provided by authors were used in agreement with the PRISMA statement. The end points were all-cause death, cardiovascular death, and hospitalization for cardiovascular cause.

    Results: Ten studies were included, reporting data on 11 cohorts and 9289 patients (age 66±12 years, 77% men, 60% ischemic heart failure, 85% with left ventricular ejection fraction <40%). High-sensitivity troponin T data were available for all patients, whereas only 209 patients also had high-sensitivity troponin I assayed. When added to a prognostic model including established risk markers (sex, age, ischemic versus nonischemic etiology, left ventricular ejection fraction, estimated glomerular filtration rate, and N-terminal fraction of pro-B-type natriuretic peptide), high-sensitivity troponin T remained independently associated with all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.41–1.55), cardiovascular mortality (hazard ratio, 1.40; 95% confidence interval, 1.33–1.48), and cardiovascular hospitalization (hazard ratio, 1.42; 95% confidence interval, 1.36–1.49), over a median 2.4-year follow-up (all P<0.001). High-sensitivity troponin T significantly improved risk prediction when added to a prognostic model including the variables above. It also displayed an independent prognostic value for all outcomes in almost all population subgroups. The area under the curve–derived 18 ng/L cutoff yielded independent prognostic value for the 3 end points in both men and women, patients with either ischemic or nonischemic etiology, and across categories of renal dysfunction.

    Conclusions: In chronic heart failure, high-sensitivity troponin T is a strong and independent predictor of all-cause and cardiovascular mortality, and of hospitalization for cardiovascular causes, as well. This biomarker then represents an additional tool for prognostic stratification.

  • 160.
    Aimo, Alberto
    et al.
    Scuola Super Sant Anna, Pisa, Italy.
    Januzzi, James L.
    Massachusetts Gen Hosp, Harvard Clin Res Inst, Boston, MA USA.
    Vergaro, Giuseppe
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana G Monasterio, Pisa, Italy.
    Ripoli, Andrea
    Fdn Toscana G Monasterio, Pisa, Italy.
    Latini, Roberto
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Masson, Serge
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Magnoli, Michela
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Anand, Inder S.
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN USA; VA Med Ctr, Dept Cardiol, Minneapolis, MN USA.
    Cohn, Jay N
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN USA.
    Tavazzi, Luigi
    ES Hlth Sci Fdn, GVM Hosp Care & Res, Cotignola, Italy.
    Tognoni, Gianni
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Gravning, Jørgen
    Oslo Univ Hosp, Dept Cardiol, Oslo, Norway; Univ Oslo, Ctr Heart Failure Res, Oslo, Norway.
    Ueland, Thor
    Oslo Univ Hosp, Res Inst Internal Med, Rikshosp, Oslo, Norway; Univ Oslo, Fac Med, Oslo, Norway; Univ Tromso, KG Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway .
    Nymo, Ståle H
    Oslo Univ Hosp, Res Inst Internal Med, Rikshosp, Oslo, Norway.
    Rocca, Hans-Peter Brunner-La
    Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherland.
    Bayes-Genis, Antoni
    Hosp Badalona Germans Trias & Pujol, Barcelona, Spain.
    Lupón, Josep
    Hosp Badalona Germans Trias & Pujol, Barcelona, Spain.
    de Boer, Rudolf A.
    Univ Med Ctr Groningen, Groningen, Netherlands.
    Yoshihisa, Akiomi
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Takeishi, Yasuchika
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Egstrup, Michael
    Copenhagen Univ Hosp, Dept Cardiol, Rigshosp, Copenhagen, Denmark.
    Gustafsson, Ida
    Copenhagen Univ Hosp, Dept Cardiol, Rigshosp, Copenhagen, Denmark.
    Gaggin, Hanna K.
    Massachusetts Gen Hosp, Harvard Clin Res Inst, Boston, MA USA.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Huber, Kurt
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Tentzeris, Ioannis
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Wilson Tang, W. H.
    Cleveland Clin, Heart & Vasc Inst, Cleveland, OH USA.
    Grodin, Justin L
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Div Cardiol, Dallas, TX USA.
    Passino, Claudio
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana G Monasterio, Pisa, Italy.
    Emdin, Michele
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana G Monasterio, Pisa, Italy.
    High-sensitivity troponin T, NT-proBNP and glomerular filtration rate: A multimarker strategy for risk stratification in chronic heart failure2019In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 277, p. 166-172, article id S0167-5273(18)32769-4Article in journal (Refereed)
    Abstract [en]

    Background: In a recent individual patient data meta-analysis, high-sensitivity troponin T (hs-TnT) emerged as robust predictor of prognosis in stable chronic heart failure (HF). In the same population, we compared the relative predictive performances of hs-TnT, N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP), hs-C-reactive protein (hs-CRP), and estimated glomerular filtration rate (eGFR) for prognosis.

    Methods and results: 9289 patients (66 ± 12 years, 77% men, 85% LVEF <40%, 60% ischemic HF) were evaluated over a 2.4-year median follow-up. Median eGFR was 58 mL/min/1.73 m2 (interquartile interval 46–70; n = 9220), hs-TnT 16 ng/L (8–20; n = 9289), NT-proBNP 1067 ng/L (433–2470; n = 8845), and hs-CRP 3.3 mg/L (1.4–7.8; n = 7083). In a model including all 3 biomarkers, only hs-TnT and NT-proBNP were independent predictors of all-cause and cardiovascular mortality and cardiovascular hospitalization. hs-TnT was a stronger predictor than NT-proBNP: for example, the risk for all-cause death increased by 54% per doubling of hs-TnT vs. 24% per doubling of NT-proBNP. eGFR showed independent prognostic value from both hs-TnT and NT-proBNP. The best hs-TnT and NT-proBNP cut-offs for the prediction of all-cause death increased progressively with declining renal function (eGFR ≥ 90: hs-TnT 13 ng/L and NT-proBNP 825 ng/L; eGFR < 30: hs-TnT 40 ng/L and NT-proBNP 4608 ng/L). Patient categorization according to these cut-offs effectively stratified patient prognosis across all eGFR classes.

    Conclusions: hs-TnT conveys independent prognostic information from NT-proBNP, while hs-CRP does not. Concomitant assessment of eGFR may further refine risk stratification. Patient classification according to hs-TnT and NT-proBNP cut-offs specific for the eGFR classes holds prognostic significance.

  • 161.
    Aittomäki, Minna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Winell, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Grammatisk språkförståelse vid fyra år - testar vi det vi tror?: En jämförande studie av två grammatiska språkförståelsetest2011Independent thesis Advanced level (degree of Master (One Year)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Many studies have investigated the development of children's language production, yet knowledge about how and when language comprehension develops is scarce. Researchers are agreed that comprehension generally precedes production, even though some grammatical structures are produced before the child fully comprehends them. Testing language comprehension is difficult, requiring the child to perform some kind of action in order to show his or her understanding. The aim of this study is to examine two grammatical comprehension tests, Nya SIT and TROG-2, and to compare both their content, and the results they generate. Seventy-six monolingual Swedish and bilingual 4-year-old children were tested with both tests. The conclusion is that the results of the two tests for all the children correlate fairly well, 0.7 according to Spearman's rank correlation. The correlation for the bilingual children is 0.6 and for the monolingual Swedish children 0.5. A regression analysis shows that language is the factor that has the greatest influence on the results, and that gender and age have less influence. The analysis of the test items shows that TROG-2 is a more thorough test of grammar than Nya SIT which only partly reveals the child's understanding of grammar.

  • 162.
    Ajalloueian, Fatemeh
    et al.
    Tech Univ Denmark, DTU Food, Nanobio Sci Res Grp, Lyngby, Denmark.
    Lemon, Greg
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Chronakis, Ioannis S.
    Tech Univ Denmark, DTU Food, Nanobio Sci Res Grp, Lyngby, Denmark.
    Fossum, Magdalena
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden; Karolinska Inst, Ctr Mol Med, CMM 02, Stockholm, Sweden; Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Dept Paediat Surg, Sect Urol, Stockholm, Sweden.
    Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder2018In: Nature reviews. Urology, ISSN 1759-4812, E-ISSN 1759-4820, Vol. 15, no 3, p. 155-174Article, review/survey (Refereed)
    Abstract [en]

    The urinary bladder is a complex organ with the primary functions of storing urine under low and stable pressure and micturition. Many clinical conditions can cause poor bladder compliance, reduced capacity, and incontinence, requiring bladder augmentation or use of regenerative techniques and scaffolds. To replicate an organ that is under frequent mechanical loading and unloading, special attention towards fulfilling its biomechanical requirements is necessary. Several biological and synthetic scaffolds are available, with various characteristics that qualify them for use in bladder regeneration in vitro and in vivo, including in the treatment of clinical conditions. The biomechanical properties of the native bladder can be investigated using a range of mechanical tests for standardized assessments, as well as mathematical and computational bladder biomechanics. Despite a large body of research into tissue engineering of the bladder wall, some features of the native bladder and the scaffolds used to mimic it need further elucidation. Collection of comparable reference data from different animal models would be a helpful tool for researchers and will enable comparison of different scaffolds in order to optimize characteristics before entering preclinical and clinical trials.

  • 163.
    Ajeganova, Sofia
    et al.
    Karolinska Inst, Dept Med Huddinge, S-14186 Stockholm, Sweden..
    Tesfa, Daniel
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, S-14186 Stockholm, Sweden.;Roche AB, Med Affairs, S-10074 Stockholm, Sweden..
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Fadeel, Bengt
    Karolinska Inst, Inst Environm Med, Unit Mol Toxicol, S-17177 Stockholm, Sweden..
    Vedin, Inger
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, S-14186 Stockholm, Sweden..
    Zignego, Anna Linda
    Univ Florence, Ctr Syst Manifestat Hepatitis Viruses, Dept Internal Med, I-50134 Florence, Italy..
    Palmblad, Jan
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, S-14186 Stockholm, Sweden..
    Effect of FCGR polymorphism on the occurrence of late-onset neutropenia and flare-free survival in rheumatic patients treated with rituximab2017In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, article id 44Article in journal (Refereed)
    Abstract [en]

    Background: The causes and mechanisms of late-onset neutropenia (LON) following rituximab treatment in patients with rheumatic diseases are not known. In this study, we aimed to investigate the role of established Fc gamma receptor gene (FCGR) polymorphisms and B-cell-activating factor (BAFF) gene promoter polymorphisms for the development of LON and for the efficacy of rituximab in patients with rheumatic diseases. Methods: A single-center case-control retrospective study was nested in a cohort of 214 consecutive patients with rheumatic diseases treated with rituximab. Eleven patients presented with LON. Fifty non-LON control subjects were matched by diagnosis, age, sex, and treatments. Single-nucleotide polymorphisms of FCGR (FCGR2A 131H/R, FCGR2B 232I/T, FCGR3A 158V/F) and BAFF promoter polymorphism -871C/T were analyzed with polymerase chain reaction-based techniques, and serum immunoglobulin M (IgM) and BAFF levels were analyzed by enzyme-linked immunosorbent assay. Flare-free survival was related to LON occurrence and polymorphisms. Results: The FCGR3A V allele, but not other FCGR polymorphisms, correlated with the occurrence of LON; each V allele conferred a fourfold increased OR for LON (p = 0.017). FCGR3A 158V/V and presentation with LON were associated with a longer flare-free survival (p = 0.023 and p = 0.031, respectively). FCGR3A 158V/V was related to lower IgM levels (p = 0.016). Serum BAFF levels showed no relationship with LON and BAFF -871C/T promoter polymorphism. There was a tendency toward longer flare-free survival in patients with the BAFF -871T/T allotype compared with the C/T or C/C allotypes (p = 0.096). Conclusions: The results of the present study suggest that presentation with LON may be a result of the intrinsic efficacy of rituximab in patients with rheumatic diseases. LON could indicate a longer biological and therapeutic activity of rituximab modulated by a certain genotypic polymorphism: the high-affinity FCGR3A V allele. This genotype and the occurrence of LON are both related to longer flare-free survival, suggestive of common mechanisms for LON and duration of response to rituximab. The role of the BAFF -871C/T promoter polymorphism in LON occurrence is unclear.

  • 164.
    Ajithkumar, Thankamma
    et al.
    Cambridge Univ Hosp, Dept Oncol, Cambridge, England.
    Horan, Gail
    Cambridge Univ Hosp, Dept Oncol, Cambridge, England.
    Padovani, Laetitia
    Assistance Publ Hop Marseille, Dept Radiat Oncol, Marseille, France.
    Thorp, Nicky
    Clatterbridge Canc Ctr, Dept Oncol, Liverpool, Merseyside, England.
    Timmermann, Beate
    Univ Essen Gesamthsch, West German Proton Ctr, Essen, Germany.
    Alapetite, Claire
    Inst Curie, Dept Radiat Oncol, Paris, France;Inst Curie, Proton Ctr, Paris, France;Inst Curie, Dept Radiat Oncol, Orsay, France;Inst Curie, Proton Ctr, Orsay, France.
    Gandola, Lorenza
    Fdn IRCCS Ist Nazl Tumori, Dept Radiat Oncol, Milan, Italy.
    Ramos, Monica
    Hosp Univ Vall dHebron, Barcelona, Spain.
    Van Beek, Karen
    UZ Leuven, Radiotherapie Oncol, Leuven, Belgium.
    Christiaens, Melissa
    UZ Leuven, Radiotherapie Oncol, Leuven, Belgium.
    Lassen-Ramshad, Yasmin
    Aarhus Univ Hosp, Danish Ctr Particle Therapy, Aarhus, Denmark.
    Magelssen, Henriette
    Norwegian Radium Hosp, Oslo Univ Hosp, Dept Oncol, Oslo, Norway.
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Saran, Frank
    Royal Marsden Hosp, Dept Oncol, Sutton, Surrey, England.
    Rombi, Barbara
    Santa Chiara Hosp, Proton Therapy Ctr, Trento, Italy.
    Kortmann, Rolf
    Univ Leipzig, Dept Radiat Oncol, Leipzig, Germany.
    Janssens, Geert O.
    Univ Med Ctr Utrecht, Dept Radiat Oncol, Utrecht, Netherlands;Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands.
    SIOPE - Brain tumor group consensus guideline on craniospinal target volume delineation for high-precision radiotherapy2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 128, no 2, p. 192-197Article in journal (Refereed)
    Abstract [en]

    Objective: To develop a consensus guideline for craniospinal target volume (TV) delineation in children and young adults participating in SIOPE studies in the era of high-precision radiotherapy. Methods and materials: During four consensus meetings (Cambridge, Essen, Liverpool, and Marseille), conventional field-based TV has been translated into image-guided high-precision craniospinal TV by a group of expert paediatric radiation oncologists and enhanced by MRI images of liquor distribution. Results: The CTVcranial should include the whole brain, cribriform plate, most inferior part of the temporal lobes, and the pituitary fossa. If the full length of both optic nerves is not included, the dose received by different volumes of optic nerve should be recorded to correlate with future patterns of relapse (no consensus). The CTVcranial should be modified to include the dural cuffs of cranial nerves as they pass through the skull base foramina. Attempts to spare the cochlea by excluding CSF within the internal auditory canal should be avoided. The CTVspinal should include the entire subarachnoid space, including nerve roots laterally. The lower limit of the spinal CTV is at the lower limit of the thecal sac, best visible on MRI scan. There is no need to include sacral root canals in the spinal CTV. Conclusion: This consensus guideline has the potential to improve consistency of craniospinal TV delineation in an era of high-precision radiotherapy. This proposal will be incorporated in the RTQA guidelines of future SIOPE-BTG trials using CSI.

  • 165.
    Akca, Ozan
    et al.
    Univ Louisville, Dept Anesthesiol & Perioperat Med, Neurosci ICU, Louisville, KY 40292 USA..
    Ball, Lorenzo
    Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Belda, F. Javier
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Biro, Peter
    Univ Hosp Zurich, Inst Anesthesiol, Zurich, Switzerland..
    Cortegiani, Andrea
    Univ Palermo, Policlin Paolo Giaccone, Sect Anesthesia Analgesia Intens Care & Emergency, Dept Biopathol & Med Biotechnol DIBIMED, Palermo, Italy..
    Eden, Arieh
    Lady Davis Carmel Med Ctr, Dept Anesthesiol Crit Care & Pain Med, Haifa, Israel..
    Ferrando, Carlos
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Gattinoni, Luciano
    Gottingen Univ, Dept Anesthesiol Emergency & Intens Care Med, Gottingen, Germany..
    Goldik, Zeev
    Gregoretti, Cesare
    Univ Palermo, Policlin Paolo Giaccone, Sect Anesthesia Analgesia Intens Care & Emergency, Dept Biopathol & Med Biotechnol DIBIMED, Palermo, Italy..
    Hachenberg, Thomas
    Otto von Guericke Univ, Dept Anaesthesiol & Intens Care Med, Magdeburg, Germany..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hopf, Harriet W.
    Univ Utah, Dept Anesthesiol, Salt Lake City, UT USA..
    Hunt, Thomas K.
    Univ Calif San Francisco, Div Gen Surg, San Francisco, CA 94143 USA..
    Pelosi, Paolo
    Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Qadan, Motaz
    Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Cambridge, MA 02138 USA..
    Sessler, Daniel I.
    Cleveland Clin, Inst Anesthesiol, Dept Outcomes Res, Cleveland, OH 44106 USA..
    Soro, Marina
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Sentürk, Mert
    Istanbul Univ, Istanbul Sch Med, Dept Anaesthesiol & Reanimat, Istanbul, Turkey..
    WHO Needs High FIO2?2017In: TURKISH JOURNAL OF ANAESTHESIOLOGY AND REANIMATION, ISSN 2149-0937, Vol. 45, no 4, p. 181-192Article in journal (Refereed)
    Abstract [en]

    World Health Organization and the United States Center for Disease Control have recently recommended the use of 0.8 FIO2 in all adult surgical patients undergoing general anaesthesia, to prevent surgical site infections. This recommendation has arisen several discussions: As a matter of fact, there are numerous studies with different results about the effect of FIO2 on surgical site infection. Moreover, the clinical effects of FIO2 are not limited to infection control. We asked some prominent authors about their comments regarding the recent recommendations

  • 166.
    Akerlund, Emma
    et al.
    Inst för Experimentell och Klinisk medicin, Linköping.
    Huss, Fredrik R M
    Inst för Experimentell och Klinisk medicin, Linköping.
    Sjöberg, Folke
    Inst för Experimentell och Klinisk medicin, Linköping.
    Burns in Sweden: an analysis of 24,538 cases during the period 1987-2004.2007In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 33, no 1, p. 31-6Article in journal (Refereed)
    Abstract [en]

    Burn care is always progressing, but there is little epidemiological information giving a clear picture of the current number of treated burns in Sweden. This study was conducted to provide an update of patients admitted to hospital with burns in Sweden. Data were obtained for all patients who were admitted to hospitals with a primary or secondary diagnosis of burns (ICD-9/10 codes) from 1 January 1987 to 31 December 2004; 24,538 patients were found. Most of the patients were male (69%), giving a male:female ratio of 2.23:1. Children in the age-group 0-4 years old predominated, and accounted for 27% of the study material. The median length of stay was 3 days. Throughout the period 740 patients (3%) died of their burns. Significant reductions in mortality, incidence, and length of stay were seen during the study, which correlates well with other studies. However, most of the reductions were in the younger age-groups. Men accounted for the improved mortality, as female mortality did not change significantly. We think that the improvement in results among patients admitted to hospital after burns is a combination of preventive measures, improved treatment protocols, and an expanding strategy by which burned patients are treated as outpatients.

  • 167. Akerstedt, T.
    et al.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Gruber, G.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Schwarz, J.
    What does good sleep mean in terms of macro and microstructure of sleep in women and how does age affect this relation?2014In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 23, p. 240-240Article in journal (Other academic)
  • 168.
    Akerstedt, T.
    et al.
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden.;Stockholm Univ, Stress Res Inst, Stockholm, Sweden..
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Gruber, G.
    Siesta Grp, Vienna, Austria..
    Schwarz, J.
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden..
    The polysomnographical characteristics of women who have sought medical help for sleep problems - a large study of sleep macro and micro architeture2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, p. 90-90Article in journal (Other academic)
  • 169.
    Akerstedt, T.
    et al.
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Schwarz, J.
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    The change in sleepiness across 10 years of aging and its relation to changes in polysomnographic variables2017In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 40, no Supplement 1, p. E8-E8Article in journal (Other academic)
  • 170.
    Akerstedt, Torbjorn
    et al.
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Schwarz, Johanna
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Gruber, Georg
    Siesta Grp, Vienna, Austria.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Women with both sleep problems and snoring show objective impairment of sleep2018In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 51, p. 80-84Article in journal (Refereed)
    Abstract [en]

    Objective: Combined insomnia and obstructive sleep apnea has been the focus of considerable research with respect to its health effects. A related issue is whether sleep disturbances in combination with snoring might exert effects on objective sleep variables in the non-clinical general population. The purpose of the present study was to investigate the polysomnographical characteristics of individuals who had sought medical help for both disturbed sleep and for snoring. No previous work of this type has been carried out. Method: For this study we used a representative set of data of 384 women with one night of in-home PSG. We identified those individuals who had sought medical help for sleep problems (SL), individuals that had sought help for snoring (SN), as well as those that had sought help for either both (Combined), or for neither (Control). Results: Our results yielded an N of 46, 16, 21, and 301 individuals, respectively. A one-factor analysis of variance showed significant main effects on N1% (F = 10.2, p < 0.001), N3% (F = 2.7, p < 0.05), AHI/h (F = 5.5, p < 0.001), and a delta power measure (F = 3.8, p < 0.05). The combined group showed significantly higher levels than the other groups for N1% (29% vs < 21%), AHI/h (19/h vs < 10/h) and lower levels for N3%, and a measure of delta power. Reported sleep quality measures did not show the same pattern, since the highest/lowest value were found for either the group presenting snoring alone or sleep problems alone. Conclusion: We concluded that individuals who had sought help for both insomnia and snoring showed impaired sleep in terms of PSG and that this was not reflected in ratings of sleep or health. This suggests that simultaneous sleep disturbances and snoring may potentiate each other to cause impaired sleep, yet the mechanism still needs to be elucidated.

  • 171. Akeus, Paulina
    et al.
    Langenes, Veronica
    von Mentzer, Astrid
    Yrlid, Ulf
    Sjoling, Asa
    Saksena, Pushpa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Raghavan, Sukanya
    Quiding-Jarbrink, Marianne
    Altered chemokine production and accumulation of regulatory T cells in intestinal adenomas of APC(Min/+) mice2014In: Cancer Immunology and Immunotherapy, ISSN 0340-7004, E-ISSN 1432-0851, Vol. 63, no 8, p. 807-819Article in journal (Refereed)
    Abstract [en]

    Tumor progression in the colon moves from aberrant crypt foci to adenomatous polyps to invasive carcinomas. The composition of the tumor-infiltrating leukocyte population affects the ability of the immune system to fight the tumor. T cell infiltration into colorectal adenocarcinomas, particularly T helper 1 (Th1) type T cells as well as increased regulatory T cell (Treg) frequencies, is correlated with improved prognosis. However, whether Th1 cells and Tregs are already present at the adenoma stage is not known. In this study, the APC(Min/+) mouse model of intestinal adenomatous polyposis was used to investigate tumor-associated lymphocyte subsets and the mechanisms of their accumulation into gastrointestinal adenomas. Compared to unaffected tissue, adenomas accumulated CD4(+)FoxP3(+) putative Treg in parallel with lower frequencies of conventional T cells and B cells. The accumulation of Treg was also observed in human adenomatous polyps. Despite high Treg numbers, the function of conventional T cells present in the APC(Min/+) adenomas was not different from those in the unaffected tissue. Adenomas displayed an altered chemokine balance, with higher CCL17 and lower CXCL11 and CCL25 expression than in the unaffected tissue. In parallel, CXCR3(+) Tregs were largely absent from adenomas. The data indicate that already in early stages of tumor development, the balance of lymphocyte-recruiting chemokines is altered possibly contributing to the observed shift toward higher frequencies of Treg.

  • 172.
    Akhter, Tansim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Carotid Artery Wall Layer Dimensions during and after Pre-eclampsia: An investigation using non-invasive high-frequency ultrasound2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pre-eclampsia is associated with increased risk of cardiovascular disease (CVD) later in life. The ‘gold standard’ for estimating cardiovascular risk - ultrasound assessment of the common carotid artery intima-media thickness (CCA-IMT) - does not convincingly demonstrate this increased risk. The aim of this thesis was to examine whether high-frequency (22 MHz) ultrasound assessment of the individual CCA intima and media layers and calculation of the intima/media (I/M) ratio - can indicate the increased cardiovascular risk after pre-eclampsia. After validation of the method in premenopausal women with systemic lupus erythematosus (SLE) who have a recognized increased risk of CVD, women during and after normal and preeclamptic pregnancies were investigated.

    Assessment of the individual artery wall layers reliably demonstrated the increased cardiovascular risk in premenopausal women with SLE, while CCA-IMT did not. The artery wall layer dimensions in women with SLE were comparable to those of postmenopausal women without SLE and were 30 years older.

    Among the women with normal pregnancies negative changes to the artery wall later on in the pregnancy were seen in those with lower serum estradiol, older age, higher body mass index or higher blood pressure early in the pregnancy. About one year postpartum, both the mean intima thickness and the I/M ratio had improved, compared to values during pregnancy. These findings support the theory that normal pregnancy is a stress on the vascular system.

    Women who developed pre-eclampsia (mean age 31 years) had thicker intima layers, thinner media layers and higher I/M ratios, both at diagnosis and one year postpartum, than women with normal pregnancies, indicating increased cardiovascular risk.

    Women with a history of severe pre-eclampsia (mean age 44 years; mean 11 years since the last delivery) had thicker intima layers and higher I/M ratios than women with a history of normal pregnancies, indicating long-standing negative vascular effects.

    Assessment of individual CCA wall layers, but not of CCA-IMT, provided clear evidence of the well-known increased cardiovascular risk in women with SLE or pre-eclampsia. The method has the potential to become an important tool in reducing cardiovascular morbidity and mortality in these women through early diagnosis and intervention.

    List of papers
    1. Increased carotid intima thickness and decreased media thickness in premenopausal women with systemic lupus erythematosus: an investigation by non-invasive high-frequency ultrasound
    Open this publication in new window or tab >>Increased carotid intima thickness and decreased media thickness in premenopausal women with systemic lupus erythematosus: an investigation by non-invasive high-frequency ultrasound
    Show others...
    2011 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 40, no 4, p. 279-282Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE:

    To determine whether high-frequency ultrasound (US) yielding separate assessments of intima and media thickness gives additional information about the vascular morphology compared with the total common carotid artery intima-media thickness (CCA-IMT).

    METHODS:

    Using a 22 MHz US instrument, we determined the near-wall CCA-IMT, the intima and media layers, and the intima/media (I/M) ratio in 47 premenopausal women with systemic lupus erythematosus (SLE), 20 healthy women, and 17 postmenopausal women (mean ages 37, 40, and 69 years, respectively).

    RESULTS:

    In SLE, the carotid intima was thicker (0.19 ± 0.04 vs. 0.12 ± 0.02 mm), the media thinner (0.45 ± 0.12 vs. 0.68 ± 0.24 mm), the I/M ratio higher (0.45 ± 0.17 vs. 0.20 ± 0.07) (all p < 0.0001), and the CCA-IMT lower (0.64 ± 0.13 vs. 0.80 ± 0.25 mm, p < 0.01) compared to age-matched controls. The SLE patients had a thicker carotid intima compared to the postmenopausal women (0.19 ± 0.04 vs. 0.14 ± 0.03 mm, p < 0.0001) and a similar I/M ratio.

    CONCLUSION:

    Separate assessment of carotid artery wall layers demonstrated a thicker intima, thinner media, and a higher I/M ratio in women with SLE compared to healthy controls and indicated an artery wall status in SLE comparable to 30-years-older healthy women. Separate estimates of carotid intima and media layers may be preferable to CCA-IMT in SLE patients.

    National Category
    Rheumatology and Autoimmunity
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:uu:diva-163533 (URN)10.3109/03009742.2011.556146 (DOI)000294068000005 ()21469940 (PubMedID)
    Available from: 2011-12-13 Created: 2011-12-13 Last updated: 2017-12-08Bibliographically approved
    2. Artery Wall Layer Dimensions during Normal Pregnancy: A longitudinal study using non-invasive high-frequency ultrasound
    Open this publication in new window or tab >>Artery Wall Layer Dimensions during Normal Pregnancy: A longitudinal study using non-invasive high-frequency ultrasound
    Show others...
    2013 (English)In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 304, no 2, p. H229-H234Article in journal (Refereed) Published
    Abstract [en]

    The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at one year postpartum. A thick intima, thin media and high intima/media (I/M) ratio are signs of a less healthy artery wall. The mean artery wall layer dimensions remained fairly constant during pregnancy but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (p<0.001 for both). The cardiovascular risk parameters age, body mass index (BMI), and blood pressure in the first trimester were associated with higher I/M ratios, especially in the second trimester, whereas higher serum estradiol levels were significantly associated with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio, taking into account differential changes in intima and media thickness, were significantly (p<0.05-0.001) associated with all risk parameters tested except age, which was associated with increased intima thickness (p=0.02). Associations with third trimester values and changes from first to third trimesters were similar but less apparent. Thus, fairly constant mean artery wall layer dimensions during pregnancy appeared to improve postpartum. However, higher age, BMI or blood pressure, and lower serum estradiol levels in the first trimester appeared to negatively affect the artery wall, strongly suggesting that pregnancy has negative vascular effects in some women. A less likely explanation involves possible adaptation to physiological changes during and after pregnancy.

    National Category
    Obstetrics, Gynecology and Reproductive Medicine
    Identifiers
    urn:nbn:se:uu:diva-184996 (URN)10.1152/ajpheart.00670.2012 (DOI)000313587300006 ()23125216 (PubMedID)
    Available from: 2012-11-16 Created: 2012-11-16 Last updated: 2017-12-07Bibliographically approved
    3. Individual Common Carotid Artery Wall Layer Dimensions, but Not Carotid Intima-Media Thickness, Indicate Increased Cardiovascular Risk in Women With Preeclampsia: An investigation using non-invasive high-frequency ultrasound
    Open this publication in new window or tab >>Individual Common Carotid Artery Wall Layer Dimensions, but Not Carotid Intima-Media Thickness, Indicate Increased Cardiovascular Risk in Women With Preeclampsia: An investigation using non-invasive high-frequency ultrasound
    2013 (English)In: Circulation Cardiovascular Imaging, ISSN 1941-9651, E-ISSN 1942-0080, Vol. 6, no 5, p. 762-768Article in journal (Refereed) Published
    Abstract [en]

    Background Preeclampsia (PE) is associated with increased risk of cardiovascular disease later in life. Ultrasound assessment of the common carotid artery intima-media thickness (IMT) during or after PE has not indicated any increased cardiovascular risk. Methods and Results We used high-frequency ultrasound (22 MHz) to estimate the individual common carotid artery IMTs in 55 women at PE diagnosis and in 64 women with normal pregnancies at a similar stage. All were re-examined about 1 year postpartum. A thick intima, thin media, and high intima/media (I/M) ratio are signs of a less healthy artery wall. PE was associated with a significantly thicker mean common carotid artery intima, thinner media, and higher I/M ratio than in normal pregnancy (mean I/M difference, 0.21; 95% confidence interval, 0.17-0.25; P<0.0001). After adjustment for first trimester body mass index and mean arterial pressure, differences in intima thickness and I/M remained significant. About 1 year postpartum, these values had improved in both groups, but group differences remained significant (all adjusted P<0.0001). There were no significant differences in IMT between groups. In receiver-operating characteristic curve analysis, intima thickness and I/M were strongly predictive of prevalent PE (area under the curve, approximate to 0.95), whereas IMT was not (area under the curve, 0.49). Conclusions The arteries of women with PE were negatively affected during pregnancy and 1 year postpartum compared with women with normal pregnancies, indicating increased cardiovascular risk. Estimation of intima thickness and I/M ratio seem preferable to estimation of common carotid artery IMT in imaging cardiovascular risk in PE. Results from this pilot study warrant further confirmation.

    Keywords
    Preeclampsia, cardiovascular disease, common carotid artery, high-frequency ultrasound, intima/media ratio.
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-197189 (URN)10.1161/CIRCIMAGING.113.000295 (DOI)000324526900023 ()
    Available from: 2013-03-18 Created: 2013-03-18 Last updated: 2017-12-06Bibliographically approved
    4. Individual Artery Wall Layer Dimensions Indicate Increased Cardiovascular Risk in Previous Severe Preeclampsia: An investigation using non-invasive high-frequency ultrasound
    Open this publication in new window or tab >>Individual Artery Wall Layer Dimensions Indicate Increased Cardiovascular Risk in Previous Severe Preeclampsia: An investigation using non-invasive high-frequency ultrasound
    2013 (English)In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563Article in journal (Refereed) Submitted
    Abstract [en]

    Preeclampsia, especially severe preeclampsia, is associated with an increased risk of cardiovascular disease later in life. However, ultrasound assessments of the common carotid artery intima-media thickness (CCA-IMT) do not convincingly demonstrate this. The aim of this study was to assess whether the individual thickness of the CCA intima and media layers and calculation of intima/media (I/M) ratio indicate an increased cardiovascular risk in women with previous severe PE. The thicknesses of the CCA intima and media layers were obtained by non-invasive high-frequency ultrasound (22 MHz) (Collagenoson, Meudt, Germany) in 42 women with previous severe preeclampsia and 44 women with previous normal pregnancies. A thick intima, thin media and high I/M ratio are signs of a less healthy artery wall. Women with previous severe preeclampsia had a thicker mean CCA intima and a higher I/M ratio than women with previous normal pregnancies (both p < 0.0001). CCA-IMT did not differ significantly between the groups. In receiver operating characteristic (ROC) curve analysis, both intima thickness and I/M ratio clearly discriminated between women with and without previous severe preeclampsia [area under the curve (AUC) about 0.95], whereas CCA-IMT did not (AUC 0.52). Estimation of the individual CCA intima and media layers using high-frequency ultrasound and calculation of the I/M ratio clearly demonstrated the well known increased cardiovascular risk in women with previous severe preeclampsia, whereas CCA-IMT did not. This method appears preferable to measuring CCA-IMT for imaging arterial effects and the increased cardiovascular risk in women with a history of previous severe preeclampsia.

    Keywords
    Preeclampsia, cardiovascular disease, high-frequency ultrasound, intima thickness, media thickness, intima/media ratio.
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-197190 (URN)
    Available from: 2013-03-18 Created: 2013-03-18 Last updated: 2017-12-06Bibliographically approved
  • 173.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sub-clinical atherosclerosis in the common carotid artery in women with/without previous pre-eclampsia: A seven-year follow-up.2019In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, article id S0021-9150(19)30449-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Pre-eclampsia is associated with increased risk of cardiovascular disease and premature death. However, conventional common carotid artery intima-media thickness (CCA-IMT) measurement does not reflect this. In contrast, measurement of the individual CCA intima and media thicknesses clearly indicates increased vascular risk both at diagnosis and about one year after pre-eclampsia. This study examined whether individual CCA wall layers, risk factors for cardiovascular disease, and markers of endothelial dysfunction had normalized or remained unfavorable seven years after pre-eclampsia.

    METHODS: The individual CCA intima and media thicknesses were measured using 22 MHz ultrasound. Conventional cardiovascular risk factors were recorded. A thick intima, thin media and high intima/media thickness ratio (I/M) are signs of sub-clinical atherosclerosis.

    RESULTS: The median age of women with previous pre-eclampsia (cases = 23) or normal pregnancies (controls = 35) was 39/37 years. At follow-up (median about seven years), the intima remained thicker and the I/M was higher in cases than in controls [all p < 0.0001; p < 0.001 after adjustment for time to follow-up, body mass index (BMI), and mean arterial pressure (MAP)], whereas the CCA-IMT was illogically thinner. Further, BMI, MAP, hip circumference, abdominal height, serum endostatin and apolipoprotein B levels were higher in cases (all p < 0.05). Intima and I/M measurements were correlated with age, MAP, endostatin and apolipoprotein B, whereas no logical correlations were found for CCA-IMT.

    CONCLUSIONS: The arteries in cases but not controls were still adversely affected after seven years. Measuring intima thickness and I/M appears preferable to measuring CCA-IMT for demonstrating vascular risk after pre-eclampsia.

  • 174.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Artery Wall Layer Dimensions during Normal Pregnancy: A longitudinal study using non-invasive high-frequency ultrasound2013In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 304, no 2, p. H229-H234Article in journal (Refereed)
    Abstract [en]

    The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at one year postpartum. A thick intima, thin media and high intima/media (I/M) ratio are signs of a less healthy artery wall. The mean artery wall layer dimensions remained fairly constant during pregnancy but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (p<0.001 for both). The cardiovascular risk parameters age, body mass index (BMI), and blood pressure in the first trimester were associated with higher I/M ratios, especially in the second trimester, whereas higher serum estradiol levels were significantly associated with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio, taking into account differential changes in intima and media thickness, were significantly (p<0.05-0.001) associated with all risk parameters tested except age, which was associated with increased intima thickness (p=0.02). Associations with third trimester values and changes from first to third trimesters were similar but less apparent. Thus, fairly constant mean artery wall layer dimensions during pregnancy appeared to improve postpartum. However, higher age, BMI or blood pressure, and lower serum estradiol levels in the first trimester appeared to negatively affect the artery wall, strongly suggesting that pregnancy has negative vascular effects in some women. A less likely explanation involves possible adaptation to physiological changes during and after pregnancy.

  • 175.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Thicknesses of individual layers of artery wall indicate increased cardiovascular risk in severe pre-eclampsia2014In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 43, no 6, p. 675-680Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Pre-eclampsia, especially severe pre-eclampsia, is associated with an increased risk of cardiovascular disease later in life. However, ultrasound assessments of the common carotid artery intima-media thickness (CCA-IMT) do not convincingly demonstrate this. The aim of this study was to assess whether the individual thickness of the CCA intima and media layers and calculation of intima/media ratio (I/M) indicate an increased cardiovascular risk in women with previous severe pre-eclampsia.

    METHODS: The thicknesses of the CCA intima and media layers were obtained by non-invasive high-frequency ultrasound (22 MHz) in 42 women with previous severe pre-eclampsia and 44 women with previous normal pregnancies. A thick intima, thin media and high I/M are signs of a less healthy artery wall.

    RESULTS: Women with previous severe pre-eclampsia had a thicker CCA intima and a higher I/M than women with previous normal pregnancies, also after adjustment for mean arterial pressure, body mass index and CCA-IMT (all p < 0.0001). CCA-IMT did not differ significantly between the groups. In receiver operating characteristic curve analysis, intima thickness and I/M clearly discriminated between women with and without previous pre-eclampsia (c value about 0.95), whereas CCA-IMT did not (c = 0.52).

    CONCLUSIONS: Estimation of the individual CCA intima and media layers using high-frequency ultrasound and calculation of the I/M clearly demonstrated the well known increased cardiovascular risk in women with pre-eclampsia, whereas CCA-IMT did not. This method appears preferable to measuring CCA-IMT for imaging arterial effects and the increased cardiovascular risk in women with previous severe pre-eclampsia.

  • 176.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia2017In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 50, p. 93-99Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.

    METHODS: Serum sFlt1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22 MHz) ultrasonography in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, with reassessment one year postpartum. A thick intima, thin media and a high I/M ratio indicate a less healthy arterial wall.

    RESULTS: During pregnancy, higher levels of sFlt1, lower levels of PlGF and thicker intima, thinner media and higher I/M ratios were found in women with PE vs. controls (all p < 0.0001). Further, sFlt1 and the sFlt1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all p < 0.0001), but negatively correlated with media thickness (p = 0.002 and 0.03, respectively). About one year postpartum, levels of sFlt1 and the sFlt1/PlGF ratio had decreased in both groups, but compared with controls women in the PE group still had higher levels (p = 0.001 and 0.02, respectively). Further, sFlt1 levels and the sFlt1/PlGF ratio were still positively correlated with intima thickness and I/M ratio.

    CONCLUSIONS: Higher sFlt1 levels and sFlt1/PlGF ratios in women with PE were positively associated with signs of arterial aging during pregnancy. About one year postpartum sFlt1 levels and the sFlt1/PlGF ratios were still higher in the PE group, and also associated with the degree of arterial aging.

  • 177.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia.2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 241, p. 417-422Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA).

    METHODS: Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall.

    RESULTS: During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers.

    CONCLUSIONS: Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.

  • 178.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dimethylarginines correlate to common carotid artery wall layer dimensions and cardiovascular risk factors in pregnant women with and without preeclampsia2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 275, p. E69-E70Article in journal (Other academic)
  • 179.
    Akram, Frida Hosseini
    et al.
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Johansson, Bengt
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Mollerstrom, Gunnar
    Oxback Clin, Sodertalje, Sweden..
    Landgren, Britt-Marie
    Karolinska Inst, CLINTEC, Stockholm, Sweden..
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Skjoldebrand-Sparre, Lottie
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Incidence of Subclinical Hypothyroidism and Hypothyroidism in Early Pregnancy2017In: Journal of Women's Health, ISSN 1540-9996, E-ISSN 1931-843X, Vol. 26, no 11, p. 1231-1235Article in journal (Refereed)
    Abstract [en]

    Background: Untreated and subclinical hypothyroidism (SCH) has been associated with adverse pregnancy complications such as increased risk of miscarriage, hypertension, preeclampsia, and preterm delivery. However, in Sweden, screening for thyroid dysfunction during pregnancy is only recommended for women with a high risk of thyroid disease. Therefore, the aim of this study was to determine the incidence of clinical and SCH in women in the first trimester of pregnancy.

    Materials and Methods: In this prospective study, 1298 pregnant women were divided into three groups: one unselected general screening group (n=611), one low-risk group comprising women without risk factors for thyroid disorder (n=511), and one high-risk group comprising women with an inheritance or suspicion of thyroid disease or undergoing treatment for thyroid disease (n=88). Serum was obtained up to gestational week 13, and thyrotropin (TSH) was analyzed.

    Results: The incidences of thyroid dysfunction in the three screening groups were 9.8% in the general screening group, 9.6% in the low-risk group, and 10.2%, p=0.948, in the high-risk group. In the women with known hypothyroidism on levothyroxine treatment, 50.6% had serum TSH levels above 2.0mIU/L.

    Conclusions: High-risk screening is not useful in predicting which women are at risk of thyroid disease in early pregnancy since approximate to 10% of women with SCH or hypothyroidism could not be diagnosed in this way.

  • 180.
    Akre, Olof
    et al.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Garmo, Hans
    Regional Oncological Center, Uppsala, Sweden.
    Adolfsson, Jan
    Oncological Center, CLINTEC Department, Karolinska Institutet, Stockholm, Sweden.
    Lambe, Mats
    Oncological Center, CLINTEC Department, andDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bratt, Ola
    Department of Urology, Helsingborg Hospital, Lund University, Sweden.
    Stattin, Pär
    Department of Surgical and Perioperative sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Mortality Among Men with Locally Advanced Prostate Cancer Managed with Noncurative Intent: A Nationwide Study in PCBaSe Sweden2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 3, p. 554-563Article in journal (Refereed)
    Abstract [en]

    Background

    There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment.

    Objective

    To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent.

    Design, setting, and participants

    We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis.

    Measurements

    We followed up the patient cohort in the Cause of Death Register for ≤11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics.

    Results and limitations

    The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25–32%) for Gleason score (GS) 2–6, 41% (95% CI, 38–44%) for GS 7, 52% (95% CI, 47–57%) for GS 8, and 64% (95% CI, 59–69%) for GS 9–10. Even for men aged >85 yr at diagnosis with GS 8–10, PCa was a major cause of death: 42% (95% CI, 37–47%). Men with locally advanced disease and a PSA < 4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status.

    Conclusions

    The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors.

  • 181.
    Al Ahmadi, Ibrahim
    et al.
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Abasi, Amira
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Syed, Raza
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Broering, Dieter-C.
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Initial Experience From Implementation of Hand-Assisted Retroperitoneoscopic Live Donor Nephrectomy in Saudi Arabia2013In: Annals of Saudi Medicine, ISSN 0256-4947, E-ISSN 0975-4466, Vol. 33, no 2, p. S58-S59Article in journal (Refereed)
    Abstract [en]

    Introduction: Donor risks and morbidity are consequences of the invasiveness of donor nephrectomy procedure. The flank incision is currently the default donor nephrectomy procedure at the King Faisal Hospital in Saudi Arabia. In order to minimize the surgical-related trauma, we are implementing the hand-assisted retroperitoneoscopic live donor nephrectomy (HARS), which previously has been shown to promote donor safety. Here, we present our initial experience with this procedure. Material and Methods: The HARS technique was implemented at our center in 2010. We present a survey of our data regarding operative characteristics as well as donor/recipient outcome. Given the small number of cases, data are presented as median with range. Results: Between 2010 and 2013, 18 left -sided HARS nephrectomy procedures were performed. The median donor age and BMI were 26.5 (18-43) and 24.1 (18.7-30.7), respectively. The median hospitalization was 4 days (3-5). One donor presented wound seroma in the pfannenstiell incision with no need for intervention. Another donor presented unspecific thoracoabdominal pain on postoperative day 2. No intra-and postoperative bleeding was observed. The median creatinine at the current follow-up was 90 mu mol/L with 100% graft survival. Conclusion: HARS is a feasible and safe technique. However, for implementation of HARS as the default donor nephrectomy procedure more practice is needed.

  • 182. Al Hashmi, S.
    et al.
    Sadeghi, B.
    Hassan, Z.
    Abedi-Valugerdi, M.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hassan, M.
    Omega-3 from fish oil augments GVHD through the enhancement of chemotherapy conditioning regimen and selective FoxP3 depletion2013In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 48, no 6, p. 843-848Article in journal (Refereed)
    Abstract [en]

    Omega-3 is known to enhance the effects of several chemotherapeutic agents and to exert several immunoregulatory actions In the present study, we evaluated the effects of a 21-day feeding regimen with omega-3-rich fish oil (FO) and its corresponding control, omega-6 rich corn oil (CO), on the BU-CY conditioning and the development of GVHD after BMT in mice. Before conditioning, FO, but not CO, feeding caused a significant attenuation in the number and functionality of splenic FoxP3+ T regulatory cells (Treg). FO feeding also enhanced the effects of the conditioning through severe depletion of Treg cells in the spleen and CD11b+ myeloid cells in both the BM and spleen. Consequently, FO-fed animals conditioned with BU-CY showed exacerbated GVHD following transplantation with allogeneic BM and splenic cells. In contrast, identical transplantation in CO-fed mice resulted in poor engraftment and body weight loss. Moreover, in standard-fed recipients, BMT with cells from FO-fed donors resulted in moderate GVHD and improved the survival time, whereas BMT with cells from CO-fed donors shortened the survival time and caused anemia. We conclude that food supplements should be considered in patients undergoing BMT and/or chemotherapy treatment.

  • 183.
    Alabas, O. A.
    et al.
    Univ Leeds, Leeds, W Yorkshire, England..
    Rutherford, M.
    Univ Leicester, Leicester, Leics, England..
    Hall, M.
    Univ Leeds, Leeds, W Yorkshire, England..
    Szummer, K.
    Karolinska Univ Hosp, Dept Med H7, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gale, C. P.
    Univ Leeds, Leeds, W Yorkshire, England..
    Jernberg, T.
    Karolinska Univ Hosp, Dept Med H7, Stockholm, Sweden..
    Lower long term relative survival and higher excess mortality in women and in elderly after acute myocardial infarction: a national cohort study using 180,368 cases from the SWEDEHEART registry2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no Suppl. 1, p. 1385-1385Article in journal (Refereed)
  • 184.
    Alabas, Oras A.
    et al.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Bioinformat Ctr, MRC, Leeds, W Yorkshire, England..
    Gale, Chris P.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Bioinformat Ctr, MRC, Leeds, W Yorkshire, England.;York Teaching Hosp NHS Fdn Trust, Dept Cardiol, York, N Yorkshire, England..
    Hall, Marlous
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Bioinformat Ctr, MRC, Leeds, W Yorkshire, England..
    Rutherford, Mark J.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Szummer, Karolina
    Dept Med, Huddinge, Sweden..
    Lawesson, Sofia Sederholm
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Alfredsson, Joakim
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Karolinska Inst, Danderyds Hosp, Dept Clin Sci, Stockholm, Sweden..
    Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e007123Article in journal (Refereed)
    Abstract [en]

    Background - This study assessed sex differences in treatments, all-cause mortality, relative survival, and excess mortality following acute myocardial infarction.

    Methods and Results - A population-based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART [Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies]) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline-indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all-cause mortality adjusted for age, year of hospitalization, and comorbidities for ST-segment-elevation myocardial infarction (STEMI) and non-STEMI at 1 year (mortality rate ratio: 1.01 [95% confidence interval (CI), 0.96-1.05] and 0.97 [95% CI, 0.95-.99], respectively) and 5 years (mortality rate ratio: 1.03 [95% CI, 0.99-1.07] and 0.97 [95% CI, 0.95-.99], respectively), excess mortality was higher among women compared with men for STEMI and non-STEMI at 1 year (EMRR: 1.89 [95% CI, 1.66-2.16] and 1.20 [95% CI, 1.16-1.24], respectively) and 5 years (EMRR: 1.60 [95% CI, 1.48-1.72] and 1.26 [95% CI, 1.21-1.32], respectively). After further adjustment for the use of guideline-indicated treatments, excess mortality among women with non-STEMI was not significant at 1 year (EMRR: 1.01 [95% CI, 0.97-1.04]) and slightly higher at 5 years (EMRR: 1.07 [95% CI, 1.02-1.12]). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 [95% CI, 1.26-1.62]) and 5 years (EMRR: 1.31 [95% CI, 1.19-1.43]).

    Conclusions - Women with acute myocardial infarction did not have statistically different all-cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline-indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women.

  • 185.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Alzheimerin tauti: (Alzheimer’s sjukdom)2012In: Patologia: (Patologi) / [ed] Mäkinen M, Carpen O, Kosma VM, Lehto VP, Paavonen T, Stenbäck F, Helsingfors: Duodecim , 2012, 1, p. 1029-1031Chapter in book (Other academic)
  • 186.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Alzheimer's disease-related lesions2013In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 33, no Suppl 1, p. S173-S179Article, review/survey (Refereed)
    Abstract [en]

    The invitation to contribute to "Alzheimer's Disease: Advances for a New Century" gave me an opportunity to briefly summarize my personal opinions about how the field of neuropathology has evolved. The goal is to briefly exemplify the changes that have influenced the way we conduct our diagnostic work as well as the way we interpret our results. From an era of histological stains, we have moved to visualization of altered proteins in predicted brain regions; we have also realized that in many aged subjects, not one but a plethora of co-pathologies are seen, and finally, we have become aware that the degenerative process is initiated much earlier than we ever suspected.

  • 187.
    Alafuzoff, Irina
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Cerebral amyloid angiopathy, hemorrhages and superficial siderosis.2008In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 39, no 10, p. 2699-700Article in journal (Refereed)
  • 188.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Frontotemporaaliset lobaariset degeneraatiot: (Frontoremporal degeneration)2012In: Patologia: (Patologi) / [ed] Mäkinen M, Carpen O, Kosma VM, Lehto VP, Paavonen T, Stenbäck F, Helsingfors: Duodecim , 2012, 1, p. 1032-1033Chapter in book (Other academic)
  • 189.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Minimal neuropathologic diagnosis for brain banking in the normal middle-aged and aged brain and in neurodegenerative disorders.2018In: Handbook of Clinical Neurology, ISSN 0072-9752, E-ISSN 2212-4152, Vol. 150, p. 131-141, article id B978-0-444-63639-3.00010-4Article in journal (Refereed)
    Abstract [en]

    Research on human brain diseases is currently often conducted on cell cultures and animals. Several questions however can only be addressed by studying human postmortem brain tissue. However, brain tissue obtained postmortem almost always displays pathology that is often related to the aging phenomenon. Thus, in order to be certain that the answers obtained are reliable, a systematic and thorough assessment of the brain tissue to be studied should be carried out. We are currently aware of several protein alterations that are found in middle-aged and aged brains that are obtained from neurologically unimpaired subjects. The most common alteration is hyperphosphorylation of τ, observed in both neurons and glial cells, in certain brain regions, followed by β-amyloid aggregation in the neuropil and vessel walls. Less common protein alterations are those noted for α-synuclein and Tar DNA-binding protein 43. It is noteworthy that these alterations, when found in excess, are diagnostic for various neurodegenerative diseases, such as Alzheimer disease, Pick disease, progressive supranuclear palsy, corticobasal degeneration, Parkinson disease, Lewy body dementia, and frontotemporal lobar degeneration. Since 1990, the neuropathology community has been aware that these protein alterations tend to progress in an orderly neuroanatomically defined manner and have thus designed a method to define a stage or a phase of the protein alteration. The neuropathology community has defined an initiation site, or neuroanatomic area that they presume the alteration originates from, and defined a presumed pattern of progression from the initiation site to other brain areas. Thus a reliable and reproducible description of each case regarding these alterations can be achieved. In addition to the above alterations, the brain tissue is also prone to various vascular alterations that should be registered as seen or not seen even if the significance of these alterations is still unclear.

  • 190.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Neuropatologinen tutkimus: Neuropatologisk undersökning2010In: Muistisairaudet: (Minnestörningar) / [ed] Erkinjuntti T, Rinne J, Soininen H, Helsingfors: Duodecim , 2010, 1, p. 438-446Chapter in book (Other academic)
  • 191.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Neuropatologinen tutkimus: Neuropatologisk undersökning2015In: Muistisairaudet: (Minnestörningar) / [ed] Erkinjuntti T, Rinne J, Soininen H, Helsingfors: Duodecim , 2015, 2, p. 426-434Chapter in book (Other academic)
  • 192.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Parkinsonin tauti ja lewynkappaledementia: (Parkinsons sjukdom)2012In: Patologia: (Patologi) / [ed] Mäkinen M, Carpen O, Kosma VM, Lehto VP, Paavonen T, Stenbäck F, Helsingfors: Duodecim , 2012, 1, p. 1031-1032Chapter in book (Other academic)
  • 193.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Rapeuttavat aivosairaudet: (Degenerativa hjärnsjukdomar)2012In: Patologia: (Patologi) / [ed] Mäkinen M, Carpen O, Kosma VM, Lehto VP, Paavonen T, Stenbäck F, Helsingfors: Duodecim , 2012, 1, p. 1023-1028Chapter in book (Other academic)
  • 194.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Techniques in neuropathology.2017In: Handbook of Clinical Neurology, ISSN 0072-9752, E-ISSN 2212-4152, Vol. 145, p. 3-7, article id B978-0-12-802395-2.00001-8Article in journal (Refereed)
    Abstract [en]

    The primary objective for a neuropathologist is the characterization of the tissue that is being assessed and thus all available techniques ranging from naked-eye examination to assessment of genetic/epigenetic characteristics are currently applied. What is observed in the tissue obtained from a diseased subject is compared with what is observed in a healthy individual and, based on the outcome, neuropathologic definitions of diseases are constructed. Thus, with the naked eye a neuropathologist can confirm that a hemorrhage is observed in the brain, by histologic examination that the hemorrhage is caused by alterations in the brain vessels and, since 1954, applying Congo red dye neuropathologists have been able to state that congophilic angiopathy is detected. Since 1984, applying immunohistochemical methods neuropathologists have been able to verify that the protein seen in the vessel walls is β-amyloid and by genetic/epigenetic analysis eventual mutation or modifications of genome might be detected. The development of new techniques is staggering and throughout this book the authors have listed techniques currently applied while assessing various disease-related hallmark lesions. In the following a general summary of techniques applied is given.

  • 195.
    Alafuzoff, Irina
    et al.
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Aho, L
    Helisalmi, S
    Mannermaa, A
    Soininen, H
    Beta-amyloid deposition in brains of subjects with diabetes2009In: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 35, no 1, p. 60-68Article in journal (Refereed)
    Abstract [en]

    AIM:

    A causative association between diabetes mellitus (DM) and Alzheimer's disease (AD) has been suggested based on clinical and epidemiological studies. One hypothesis is that the link between DM and AD is related to the function of insulin-degrading enzyme (IDE), an enzyme that degrades not only insulin and pancreatic amylin but also beta-amyloid (Abeta). Thus, in diabetics, insulin and Abeta might compete for IDE and this might lead to an increase in Abeta. The objective of this study was to test the hypothesis that hyperinsulinaemia can elevate Abeta levels and thus contribute to AD pathology in humans.

    METHODS:

    Neuropathological examination was carried out employing conventional and immunohistochemical (IHC) methods of the brains obtained post mortem from 701 aged subjects.

    RESULTS:

    The loads of IHC/Abeta, silver stained neuritic plaques (NP) and neurofibrillary tangles (NFT) were significantly higher in subjects carrying the Apolipoprotein E e4 allele. In contrast, the loads of Abeta, NPs and NFT in the brains were not influenced by hyperglycaemia when comparing 134 diabetic with 567 non-diabetic subjects.

    CONCLUSIONS:

    We conclude that the hypothesis that hyperinsulinaemia would significantly elevate the Abeta load and thus increase the extent of AD pathology cannot be supported. Our result challenges the claim that DM is a direct risk factor of developing AD. Thus further studies on pathological lesions in demented diabetics should be conducted.

  • 196.
    Alafuzoff, Irina
    et al.
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Arzberger, Thomas
    Al-Sarraj, Safa
    Bodi, Istvan
    Bogdanovic, Nenad
    Braak, Heiko
    Bugiani, Orso
    Del-Tredici, Kelly
    Ferrer, Isidro
    Gelpi, Ellen
    Giaccone, Giorgio
    Graeber, Manuel B
    Ince, Paul
    Kamphorst, Wouter
    King, Andrew
    Korkolopoulou, Penelope
    Kovács, Gábor G
    Larionov, Sergey
    Meyronet, David
    Monoranu, Camelia
    Parchi, Piero
    Patsouris, Efstratios
    Roggendorf, Wolfgang
    Seilhean, Danielle
    Tagliavini, Fabrizio
    Stadelmann, Christine
    Streichenberger, Nathalie
    Thal, Dietmar R
    Wharton, Stephen B
    Kretzschmar, Hans
    Staging of neurofibrillary pathology in Alzheimer's disease: a study of the BrainNet Europe Consortium.2008In: Brain Pathology, ISSN 1015-6305, E-ISSN 1750-3639, Vol. 18, no 4, p. 484-96Article in journal (Refereed)
    Abstract [en]

    It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and beta-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-microm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V-VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I-II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.

  • 197.
    Alafuzoff, Irina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hartikainen, Päivi
    Alpha-synucleinopathies.2017In: Handbook of Clinical Neurology, ISSN 0072-9752, E-ISSN 2212-4152, Vol. 145, p. 339-353, article id B978-0-12-802395-2.00024-9Article in journal (Refereed)
    Abstract [en]

    A neurodegenerative disorder displaying an altered α-synuclein (αS) in the brain tissue is called α-synucleinopathy (αS-pathy) and incorporates clinical entities such as Parkinson disease (PD), PD with dementia, dementia with Lewy bodies, and multiple-system atrophy. Neuroradiologic techniques visualizing αS pathology in the brain or assays of αS in the cerebrospinal fluid or blood are probably available and will be implemented in the near future but currently the definite diagnosis of αS-pathy relies on a postmortem examination of the brain. Since the 1980s immunohistochemical technique based on the use of antibodies directed to proteins of interest has become a method of choice for neuropathologic diagnosis. Furthermore, since the 1990s it has been acknowledged that progressions of most neurodegenerative pathologies follow a certain predictable time-related neuroanatomic distribution. Currently, for Lewy body disease, two staging techniques are commonly used: McKeith and Braak staging. Thus, the neuropathologic diagnosis of a αS-pathy is based on detection of altered αS in the tissue and registration of the neuroanatomic distribution of this alteration in the brain. The clinicopathologic correlation is not absolute due to the quite frequent observation of incidental and concomitant αS pathology.

  • 198.
    Alafuzoff, Irina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Kovacs, Gabor G
    Comorbidities.2017In: Handbook of Clinical Neurology, ISSN 0072-9752, E-ISSN 2212-4152, Vol. 145, p. 573-577, article id B978-0-12-802395-2.00036-5Article in journal (Refereed)
    Abstract [en]

    The term comorbidities or mixed pathologies is used when brain tissue, a surgical sample, or postmortem brain displays a mixture of protein alterations or other pathologies. Most of the alterations when seen in sufficient extent are considered causative, are related to a certain clinical phenotype, i.e., when hyperphosphorylated τ (HPτ) is observed in occipital cortex concomitant with β-amyloid (Aβ), the diagnosis is Alzheimer disease (AD). When HPτ is observed in hippocampal structures in a subject with extensive and widespread α-synuclein pathology, a Lewy body disease (LBD), the HPτ pathology is considered as a concomitant alteration. There are numerous reports indicating that when "concomitant" pathologies are seen in a subject with certain neurodegenerative diseases, the clinical phenotype might be altered. In addition there are those cases where many alterations are seen in a sparse extent, but jointly they lead to a clinical syndrome. Thus today it is not sufficient to confirm a certain pathology to be seen, i.e., AD- or LBD-related; in addition the concomitant aging-related alterations have to be looked for.

  • 199.
    Alafuzoff, Irina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Parkkinen, Laura
    Staged pathology in Parkinson's disease2014In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 20, no Suppl. 1, p. S57-S61Article in journal (Refereed)
    Abstract [en]

    There has been a tremendous development since a regional progression of pathology in subjects with Lewy bodies (LB) was initially proposed 30 years ago. The entity of dementia with Lewy bodies has been acknowledged, the main protein constituent of LBs--aggregated α-synuclein (αS)--has been identified and a stepwise progression of the pathology has been reported. Implementation of the staging strategies published provides a common ground for handling a case with a suspected α-synucleinopathy. It is always important to state the staging strategy implemented while assessing a case, as the strategy applied might influence both the reported stage of LB pathology and, ultimately, the final diagnosis of the patient.

  • 200.
    Alafuzoff, Irina
    et al.
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Parkkinen, Laura
    Al-Sarraj, Safa
    Arzberger, Thomas
    Bell, Jeanne
    Bodi, Istvan
    Bogdanovic, Nenad
    Budka, Herbert
    Ferrer, Isidro
    Gelpi, Ellen
    Gentleman, Stephen
    Giaccone, Giorgio
    Kamphorst, Wouter
    King, Andrew
    Korkolopoulou, Penelope
    Kovács, Gábor G
    Larionov, Sergey
    Meyronet, David
    Monoranu, Camelia
    Morris, Jodie
    Parchi, Piero
    Patsouris, Efstratios
    Roggendorf, Wolfgang
    Seilhean, Danielle
    Streichenberger, Nathalie
    Thal, Dietmar R
    Kretzschmar, Hans
    Assessment of alpha-synuclein pathology: a study of the BrainNet Europe Consortium.2008In: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 67, no 2, p. 125-43Article in journal (Refereed)
    Abstract [en]

    To determine the reliability of assessment of alpha-synuclein-immunoreactive (alphaS-IR) structures by neuropathologists, 28 evaluators from 17 centers of BrainNet Europe examined current methods and reproducibility of alphaS-IR evaluation using a tissue microarray (TMA) technique. Tissue microarray blocks were constructed of samples from the participating centers that contained alphaS-IR structures. Slides from these blocks were stained in each center and assessed for neuronal perikaryal inclusions, neurites, and glial cytoplasmic inclusions. The study was performed in 2 phases. First, the TMA slides were stained with the antibody of the center's choice. In this phase, 59% of the sections were of good or acceptable quality, and 4 of 9 antibodies used performed consistently. Differences in interpretation and categorization of alphaS-IR structures, however, led to differing results between the laboratories. Prior to the second phase, the neuropathologists participated in a training session on the evaluation of alphaS-IR structures. Based on the results of the first phase, selected antibodies using designated antigen retrieval methods were then applied to TMA slides in the second phase. When the designated methods of both staining and evaluation were applied, all 26 subsequently stained TMA sections evaluated were of good/acceptable quality, and a high level of concordance in the assessment of the presence or absence of specific alphaS-IR structures was achieved. A semiquantitative assessment of alphaS-IR neuronal perikaryal inclusions yielded agreements ranging from 49% to 82%, with best concordance in cortical core samples. These results suggest that rigorous methodology and dichotomized assessment (i.e. determining the presence or absence of alphaS-IR) should be applied, and that semiquantitative assessment can be recommended only for the cortical samples. Moreover, the study demonstrates that there are limitations in the scoring of alphaS-IR structures.

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