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  • 401. Naghavi, M,
    et al.
    Abajobir, AA,
    Abbafati, C
    Abbas, KM
    Abd-Allah, F
    Abera, SF
    Aboyans, V
    Adetokunboh, O
    Afshin, A
    Agrawal, A
    Ahmadi, A
    Ahmed, MB
    Ärnlöv, Johan
    Dalarna University; Karolinska institute.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Zaidi, Z
    Zaki, MES
    Zegeye, EA
    Zenebe, ZM
    Zerfu, TA
    Zhang, AL
    Zhang, X
    Zipkin, B
    Zodpey, S
    Lopez, AD,
    Murray, CJL
    Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016.2017Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 390, nr 10100, s. 1151-1210Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends.

    METHODS: We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016.

    FINDINGS: The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2-73·2) of deaths in 2016 with 19·3% (18·5-20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00-8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006-16-age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176-181) increase in deaths in ages 90-94 years and a 210% (208-212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe.

    INTERPRETATION: The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems.

    FUNDING: Bill & Melinda Gates Foundation.

  • 402. Naghavi, Moshen
    et al.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Murray, Christopher JL
    Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.2015Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, nr 9963, s. 117-171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries.

    METHODS: We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions.

    FINDINGS: Global life expectancy for both sexes increased from 65·3 years (UI 65·0-65·6) in 1990, to 71·5 years (UI 71·0-71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8-48·2) to 54·9 million (UI 53·6-56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions.

    INTERPRETATION: For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

  • 403.
    Ndjole, Annaby Moussa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Bodolea, Constantin
    Nilsen, Tom
    Gentian AS, Moss, Norway.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Flodin, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Determination of cerebrospinal fluid cystatin C on Architect ci82002010Inngår i: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 360, nr 1-2, s. 84-88Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Human cystatin C is a cysteine protease inhibitor produced by all nucleated cells in the body and the protein is present in all body fluids. The concentration in cerebrospinal fluid (CSF) is considerably higher than in plasma. Cystatin C levels seem to influence the development of Alzheimer disease (AD) and low levels in the brain are associated with an increased risk for AD. The aim of this study was to develop a high throughput assay for the quantification of cystatin C in CSF. METHODS: Antigen excess, imprecision, interference, linearity, recovery, sample stability and reference values were evaluated on Architect ci8200 (Abbott Laboratories, Abbott Park, IL, USA). RESULTS: The assay had an antigen-excess limit at 23 mg/L and was linear over the range of 0.84 to 8.33 mg/L. Results > 8.33 mg/L were automatically rerun in a higher dilution. Within-run coefficient of variation (CV) was 1.71, 1.10 and 0.79%, between day CV was 1.71, 0.39 and 1.45%, between-run CV was 0.58, 0.66 and 0.48%, and total CV was 2.49, 1.34 and 1.72% at cystatin C concentrations of 1.39, 3.17 and 6.28 mg/L, respectively. The recovery was 97-102%. No interference at a 7.5% deviation level was observed for 8.5 g/L of hemoglobin or 800 mg/L (1368 micromol/L) of bilirubin. Reference values for cystatin C in cerebrospinal fluid obtained with this method were 2.42-14.33 mg/L.

  • 404.
    Nelander, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk forskning.
    Weis, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Bergman, Lina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk forskning.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Wikström, Anna-Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk forskning. Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Cerebral Magnesium Levels in Preeclampsia; A Phosphorus Magnetic Resonance Spectroscopy Study2017Inngår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 30, nr 7, s. 667-672Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Magnesium sulfate (MgSO4) is used as a prophylaxis for eclamptic seizures. The exact mechanism of action is not fully established. We used phosphorus magnetic resonance spectroscopy (31P-MRS) to investigate if cerebral magnesium (Mg2+) levels differ between women with preeclampsia, normal pregnant, and nonpregnant women.

    METHODS: This cross-sectional study comprised 28 women with preeclampsia, 30 women with normal pregnancies in corresponding gestational week (range: 23-41 weeks) and 11 nonpregnant healthy controls. All women underwent 31P-MRS from the parieto-occipital region of the brain and were interviewed about cerebral symptoms. Differences between groups were assessed by analysis of variance and Tukey's post-hoc test. Correlations between Mg2+ levels and specific neurological symptoms were estimated with Spearman's rank test.

    RESULTS: Mean maternal cerebral Mg2+ levels were lower in women with preeclampsia (0.12 mM ± 0.02) compared to normal pregnant controls (0.14 mM ± 0.03) (P = 0.04). Nonpregnant and normal pregnant women did not differ in Mg2+ levels. Among women with preeclampsia, lower Mg2+ levels correlated with presence of visual disturbances (P = 0.04). Plasma levels of Mg2+ did not differ between preeclampsia and normal pregnancy.

    CONCLUSIONS: Women with preeclampsia have reduced cerebral Mg2+ levels, which could explain the potent antiseizure prophylactic properties of MgSO4. Within the preeclampsia group, women with visual disturbances have lower levels of Mg2+ than those without such symptoms.

  • 405.
    Nelander, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Wikström, Anna-Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Weis, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Bergman, Lina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk obstetrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Cerebral osmolytes and plasma osmolality in pregnancy and preeclampsia: a proton magnetic resonance spectroscopy study2018Inngår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 31, nr 7, s. 847-853Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Cerebral complications contribute substantially to mortality in preeclampsia. Pregnancy calls for extensive maternal adaptations, some associated with increased propensity for seizures, but the pathophysiology behind the eclamptic seizures is not fully understood. Plasma osmolality and sodium levels are lowered in pregnancy. This could result in extrusion of cerebral organic osmolytes, including the excitatory neurotransmitter glutamate, but this remains to be determined. The hypothesis of this study was that cerebral levels of organic osmolytes are decreased during pregnancy, and that this decrease is even more pronounced in women with preeclampsia.

    Method: We used proton magnetic resonance spectroscopy to compare levels of cerebral organic osmolytes, in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant controls (n=16). Cerebral levels organic osmolytes were further correlated to plasma osmolality, and plasma levels of glutamate and sodium.

    Results: Compared to non-pregnant women, women with normal pregnancy and preeclampsia had lower levels of the cerebral osmolytes myo-inositol, choline and creatine (p=0.001 or less), and all these metabolites correlated with each other (p<0.05). Women with normal pregnancies and preeclampsia had similar levels of osmolytes, except for glutamate, which was significantly lower in preeclampsia. Cerebral and plasma glutamate levels were negatively correlated with each other (p<0.008), and cerebral myo-inositol, choline and creatine levels were all positively correlated with both plasma osmolality and sodium levels (p<0.05).

    Conclusion: Our results indicate that pregnancy is associated with extrusion of cerebral organic osmolytes. This includes the excitatory neurotransmitter glutamate, which may be involved in the pathophysiology of seizures in preeclampsia.

  • 406.
    Nelson, Robert G.
    et al.
    NIDDK, Chron Kidney Dis Sect, NIH, Phoenix, AZ USA;NIDDK, Chron Kidney Dis Sect, Phoenix, AZ USA.
    Grams, Morgan E.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Ballew, Shoshana H.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Sang, Yingying
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;OptumLabs, Cambridge, MA USA;Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Azizi, Fereidoun
    Shahid Beheshti Univ Med Sci, Res Inst Endocrine Sci, Endocrine Res Ctr, Tehran, Iran;Shahid Beheshti Univ Med Sci, Res Inst Endocrine Sci, Tehran, Iran.
    Chadban, Steven J.
    Chaker, Layal
    Erasmus MC, Acad Ctr Thyroid Dis, Rotterdam, Netherlands;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Dunning, Stephan C.
    OptumLabs, Cambridge, MA USA.
    Fox, Caroline
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
    Hirakawa, Yoshihisa
    Nagoya Univ, Grad Sch Med, Dept Publ Hlth & Hlth Syst, Nagoya, Aichi, Japan.
    Iseki, Kunitoshi
    Okinawa Heart & Renal Assoc, Okinawa, Japan;Univ Hosp Ryukyus, Dialysis Unit, Nishihara, Okinawa, Japan;Okinawa Heart & Renal Assoc, Nakamura Clin, Clin Res Support Ctr, Okinawa, Japan.
    Ix, Joachim
    Univ Calif San Diego, La Jolla, CA 92093 USA;Vet Affairs San Diego Healthcare Syst, San Diego, CA USA.
    Jafar, Tazeen H.
    Duke Natl Univ Singapore Med Sch, Program Hlth Serv & Syst Res, Singapore, Singapore;Aga Khan Univ, Dept Med, Karachi, Pakistan;Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
    Koettgen, Anna
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Univ Freiburg, Fac Med, Inst Genet Epidemiol, Freiburg, Germany;Univ Freiburg, Fac Med, Inst Genet Epidemiol, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Naimark, David M. J.
    Univ Toronto, Sunnybrook Hosp, Toronto, ON, Canada.
    Ohkubo, Takayoshi
    Teikyo Univ, Sch Med, Dept Hyg & Publ Hlth, Tokyo, Japan;Teikyo Univ, Dept Hyg & Publ Hlth, Tokyo, Japan.
    Prescott, Gordon J.
    Univ Aberdeen, Sch Med Med Sci & Nutr, Med Stat Team, Aberdeen, Scotland;Univ Aberdeen, Sch Med Med Sci & Nutr, Med Stat Team, Aberdeen, Scotland;Univ Cent Lancashire, Lancashire Clin Trials Unit, Preston, Lancs, England.
    Rebholz, Casey M.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Sabanayagam, Charumathi
    Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore;Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore;Duke Natl Univ Singapore Med Sch, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
    Sairenchi, Toshimi
    Dokkyo Med Univ, Dept Publ Hlth, Mibu, Tochigi, Japan;Dokkyo Med Univ, Sch Med, Dept Publ Hlth, Mibu, Tochigi, Japan.
    Schoettker, Ben
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany;Heidelberg Univ, Network Aging Res, Heidelberg, Germany;German Canc Res Ctr, Heidelberg, Germany.
    Shibagaki, Yugo
    St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan.
    Tonelli, Marcello
    Univ Calgary, Dept Med, Calgary, AB, Canada;Univ Calgary, Dept Med, Calgary, AB, Canada.
    Zhang, Luxia
    Peking Univ, Hosp 1, Div Nephrol, Inst Nephrol, Beijing, Peoples R China;Peking Univ, Hosp 1, Beijing, Peoples R China;Peking Univ, Hosp 1, Beijing, Peoples R China;Peking Univ, Beijing, Peoples R China;Peking Univ, Beijing, Peoples R China.
    Gansevoort, Ron T.
    Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands;Univ Hosp Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands;Univ Hosp Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
    Matsushita, Kunihiro
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Woodward, Mark
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Univ Oxford, George Inst Global Hlth, Oxford, England;Univ Oxford, George Inst Global Hlth, Oxford, England;Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;George Inst Global Hlth, Sydney, NSW, Australia.
    Coresh, Josef
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Shalev, Varda
    Tel Aviv Univ, Maccabi Healthcare Serv, Div Med, Tel Aviv, Israel;Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel;Maccabi Healthcare Serv, Inst Hlth & Res & Innovat, Tel Aviv, Israel;Maccabi Healthcare Serv, Inst Hlth & Res & Innovat, Tel Aviv, Israel;Tel Aviv Univ, Tel Aviv, Israel;Tel Aviv Univ, Tel Aviv, Israel.
    Chalmers, John
    Univ Oxford, George Inst Global Hlth, Oxford, England;George Inst Global Hlth, Sydney, NSW, Australia.
    Arima, Hisatomi
    Univ Oxford, George Inst Global Hlth, Oxford, England;George Inst Global Hlth, Sydney, NSW, Australia.
    Perkovic, Vlado
    Univ Oxford, George Inst Global Hlth, Oxford, England;George Inst Global Hlth, Sydney, NSW, Australia.
    Grams, Morgan
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Polkinghorne, Kevan
    Monash Univ, Clayton, Vic, Australia.
    Atkins, Robert
    Monash Univ, Clayton, Vic, Australia.
    Chadban, Steven
    Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia;Univ Sydney, Sydney, NSW, Australia.
    Liu, Lisheng
    Beijing Hypertens League Inst, Beijing, Peoples R China;Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China.
    Zhao, Ming-Hui
    Peking Univ, Hosp 1, Beijing, Peoples R China.
    Wang, Fang
    Peking Univ, Hosp 1, Beijing, Peoples R China;Peking Univ, Hlth Sci Ctr, Beijing, Peoples R China.
    Wang, Jinwei
    Peking Univ, Hosp 1, Beijing, Peoples R China.
    Sacks, Frank M.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
    Curhan, Gary C.
    Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA;Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA.
    Shlipak, Michael
    Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA;Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA;San Francisco VA Med Ctr, San Francisco, CA USA;San Francisco VA Med Ctr, San Francisco, CA USA.
    Sarnak, Mark J.
    Katz, Ronit
    Univ Washington, Dept Med, Seattle, WA USA;Univ Washington, Dept Med, Seattle, WA USA;Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA;Univ Washington, Kidney Res Inst, Seattle, WA USA.
    Hiramoto, Jade
    Univ Calif San Francisco, Dept Surg, Div Vasc & Endovasc Surg, San Francisco, CA USA.
    Iso, Hiroyasu
    Osaka Univ, Grad Sch Med, Dept Social Med, Publ Hlth, Suita, Osaka, Japan.
    Muraki, Isao
    Osaka Ctr Canc & Cardiovasc Dis Prevent, Osaka, Japan.
    Yamagishi, Kazumasa
    Univ Tsukuba, Fac Med, Dept Publ Hlth Med, Tsukuba, Ibaraki, Japan;Univ Tsukuba, Hlth Serv Res & Dev Ctr, Tsukuba, Ibaraki, Japan.
    Umesawa, Mitsumasa
    Dokkyo Med Univ, Sch Med, Dept Publ Hlth, Mibu, Tochigi, Japan;Ibaraki Hlth Plaza, Mito, Ibaraki, Japan.
    Brenner, Hermann
    German Canc Consortium & German Canc Res Ctr, Heidelberg, Germany.
    Saum, Kai-Uwe
    German Canc Res Ctr, Heidelberg, Germany.
    Rothenbacher, Dietrich
    German Canc Res Ctr, Heidelberg, Germany;Univ Ulm, Ulm, Germany.
    Fox, Caroline S.
    NHLBI, Framingham, MA USA;Merck Res Labs, Boston, MA USA.
    Hwang, Shih-Jen
    NHLBI, Framingham, MA USA.
    Chang, Alex R.
    Geisinger Med Ctr, Dept Nephrol, Danville, PA USA;Geisinger Med Ctr, Kidney Hlth Res Inst, Danville, PA USA.
    Green, Jamie
    Singh, Gurmukteshwar
    Geisinger Med Ctr, Dept Nephrol, Danville, PA 17822 USA;Geisinger Med Ctr, Kidney Hlth Res Inst, Danville, PA 17822 USA.
    Kirchner, H. Lester
    Geisinger Med Ctr, Dept Biomed & Translat Informat, Danville, PA 17822 USA.
    Black, Corri
    Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen Ctr Hlth Data Sci, Aberdeen, Scotland.
    Marks, Angharad
    Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen Ctr Hlth Data Sci, Aberdeen, Scotland.
    Clark, Laura
    NHS Grampian, Aberdeen, Scotland.
    Fluck, Nick
    NHS Grampian, Aberdeen, Scotland.
    Cirillo, Massimo
    Univ Naples Federico II, Naples, Italy.
    Hallan, Stein
    Norwegian Univ Sci & Technol, Trondheim, Norway;Norwegian Univ Sci & Technol, Trondheim, Norway;St Olav Univ, Trondheim, Norway;St Olav Univ, Trondheim, Norway.
    Ovrehus, Marius
    Norwegian Univ Sci & Technol, Trondheim, Norway;St Olav Univ, Trondheim, Norway.
    Langlo, Knut Asbjorn
    Norwegian Univ Sci & Technol, Trondheim, Norway;St Olav Univ, Trondheim, Norway.
    Romundstad, Solfrid
    Norwegian Univ Sci & Technol, Trondheim, Norway;Levanger Hosp, Levanger, Norway.
    Irie, Fujiko
    Ibaraki Prefectural Off, Dept Hlth & Welf, Mito, Ibaraki, Japan.
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
    Young, Bessie A.
    Univ Washington, Div Nephrol, Seattle, WA 98195 USA;VA Puget Sound Hlth Care Syst, Seattle, WA USA.
    Boulware, L. Ebony
    Duke Sch Med, Dept Med, Durham, NC USA.
    Mwasongwe, Stanford
    Jackson State Univ, Jackson, MS USA.
    Watanabe, Tsuyoshi
    Fukushima Med Univ, Sch Med, Div Nephrol Hypertens Endocrinol & Diabetol Metab, Fukushima, Japan.
    Yamagata, Kunihiro
    Osaka Ctr Canc & Cardiovasc Dis Prevent, Osaka, Japan;Univ Tsukuba, Tsukuba, Ibaraki, Japan.
    Asahi, Koichi
    Iwate Med Univ, Div Nephrol & Hypertens, Morioka, Iwate, Japan.
    Chodick, Gabriel
    MaccabiTech Healthcare Serv, Epidemiol & Database Res, Tel Aviv, Israel.
    Sarnak, Mark
    Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA;Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA.
    Peralta, Carmen
    Univ Calif San Francisco, Sch Med, San Francisco VA Med Ctr, San Francisco, CA USA;Cricket Hlth, San Francisco, CA USA.
    Bottinger, Erwin
    Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    Nadkarni, Girish N.
    Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    Ellis, Stephen B.
    Icahn Sch Med Mt Sinai, Informat & Informat Technol, New York, NY 10029 USA.
    Nadukuru, Rajiv
    Icahn Sch Med Mt Sinai, Informat & Informat Technol, New York, NY 10029 USA.
    Kenealy, Timothy
    Univ Auckland, Dept Med, Auckland, New Zealand.
    Elley, C. Raina
    Univ Auckland, Gen Practice & Primary Hlth Care, Auckland, New Zealand.
    Collins, John F.
    Auckland Dist Hlth Board, Auckland, New Zealand.
    Drury, Paul L.
    Auckland Dist Hlth Board, Auckland, New Zealand.
    Asayama, Kei
    Teikyo Univ, Dept Hyg & Publ Hlth, Tokyo, Japan.
    Kikuya, Masahiro
    Teikyo Univ, Dept Hyg & Publ Hlth, Tokyo, Japan.
    Metoki, Hirohito
    Tohoku Med & Pharmaceut Univ, Div Publ Hlth Hyg & Epidemiol, Sendai, Miyagi, Japan.
    Nakayama, Masaaki
    St Lukes Int Hosp, Kidney Ctr, Tokyo, Japan.
    Iseki, Chiho
    Nakamura Clin, Okinawa, Japan;Okinawa Asia Clin Invest Synergy, Okinawa, Japan;Okinawa Heart & Renal Assoc, Nakamura Clin, Clin Res Support Ctr, Okinawa, Japan.
    Looker, Helen C.
    NIDDK, Chron Kidney Dis Sect, Phoenix, AZ USA.
    Knowler, William C.
    NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
    Bakker, Stephan J. L.
    Univ Hosp Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
    Heerspink, Hiddo J. L.
    Univ Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands.
    Bernardo, Rancho
    Jassal, Simerjot K.
    Univ Calif San Diego, Div Gen Internal Med, San Diego, CA 92103 USA;VA San Diego Healthcare, San Diego, CA USA.
    Bergstrom, Jaclyn
    Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92103 USA.
    Ix, Joachim H.
    VA San Diego Healthcare, San Diego, CA USA;Univ Calif San Diego, Div Nephrol Hypertens, San Diego, CA 92103 USA.
    Barrett-Connor, Elizabeth
    Univ Calif San Diego, Div Epidemiol, San Diego, CA 92103 USA.
    Kovesdy, Csaba P.
    Memphis Vet Affairs Med Ctr, Med Nephrol, Memphis, TN USA;Memphis Vet Affairs Med Ctr, Med Nephrol, Memphis, TN USA;Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA;Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
    Sumida, Keiichi
    Memphis Vet Affairs Med Ctr, Med Nephrol, Memphis, TN USA;Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
    Kalantar-Zadeh, Kamyar
    Univ Calif Irvine, Med Ctr, Dept Med, Div Nephrol & Hypertens, Orange, CA USA.
    Sedaghat, Sanaz
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Hoorn, Ewout J.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Dehghan, Abbas
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.
    Carrero, Juan J.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Evans, Marie
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Elinder, Carl-Gustaf
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Wettermark, Bjorn
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Wong, Tien Y.
    Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
    Cheng, Ching-Yu
    Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
    Sokor, Riswana Banu Binte Mohamed Abdul
    Singapore Eye Res Inst, Singapore, Singapore.
    Wen, Chi-Pang
    China Med Univ Hosp, Taichung, Taiwan.
    Tsao, Chwen-Keng
    MJ Hlth Management Inst, Taipei, Taiwan.
    Tsai, Min-Kuang
    Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli, Taiwan.
    Chen, Chien-Hua
    Show Chwan Mem Hosp, Digest Dis Ctr, Changhua, Taiwan.
    Hosseinpanah, Farhad
    Shahid Beheshti Univ Med Sci, Res Inst Endocrine Sci, Tehran, Iran.
    Hadaegh, Farzad
    Shahid Beheshti Univ Med Sci, Res Inst Endocrine Sci, Tehran, Iran.
    Mirbolouk, Mohammadhassan
    Johns Hopkins Med, Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA.
    Solbu, Marit Dahl
    UiT Arctic Univ Norway, Metab & Renal Res Grp, Tromso, Norway;Univ Hosp North Norway, Tromso, Norway.
    Eriksen, Bjorn Odvar
    UiT Arctic Univ Norway, Metab & Renal Res Grp, Tromso, Norway;Univ Hosp North Norway, Tromso, Norway.
    Jenssen, Trond Geir
    UiT Arctic Univ Norway, Metab & Renal Res Grp, Tromso, Norway;Oslo Univ Hosp, Dept Nephrol, Oslo, Norway.
    Eggen, Anne Elise
    UiT Arctic Univ Norway, Dept Community Med, Tromso, Norway.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Ärnlöv, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Bilo, Henk J. G.
    Univ Groningen, Dept Internal Med, Groningen, Netherlands;Univ Med Ctr Groningen, Groningen, Netherlands.
    Landman, Gijs W. D.
    Gelre Ziekenhuizen, Apeldoorn, Netherlands.
    van Hateren, Kornelis J. J.
    Langerhans Med Res Grp, Zwolle, Netherlands.
    Kleefstra, Nanne
    Langerhans Med Res Grp, Zwolle, Netherlands;Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
    Stempniewicz, Nikita
    Cuddeback, John
    Ciemins, Elizabeth
    Levey, Andrew S.
    Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA.
    Chen, Jingsha
    Kwak, Lucia
    Surapeneni, Aditya
    Development of Risk Prediction Equations for Incident Chronic Kidney Disease2019Inngår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 322, nr 21, s. 2104-2114Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    IMPORTANCE: Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.

    OBJECTIVE: To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).

    DESIGN, SETTING, AND PARTICIPANTS: Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).

    EXPOSURES: Demographic and clinical factors.

    MAIN OUTCOMES AND MEASURES: Incident eGFR of less than 60 mL/min/1.73 m(2).

    RESULTS: Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A(1c), and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.

    CONCLUSIONS AND RELEVANCE: Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

  • 407.
    Nerpin, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Riserus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Jobs, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Oxidativ stress och inflammation.
    Ingelsson, Erik
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: a cross-sectional study2012Inngår i: BMC Research Notes, E-ISSN 1756-0500, Vol. 5, nr 1, s. 537-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

     BACKGROUND: The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men.

    FINDINGS: Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2alpha [PGF2alpha]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years).

    RESULTS: In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (beta-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (beta-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (beta- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (beta-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR.

    CONCLUSION: Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.

    Fulltekst (pdf)
    fulltext
  • 408.
    Nerpin, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Jobs, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Association between glomerular filtration rate and endothelial function in an elderly community cohort2012Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, nr 1, s. 242-246Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Endothelial dysfunction is prevalent among individuals with chronic kidney disease. However, the association between glomerular filtration rate and endothelial function in the community is unclear and needs to be investigated in the general population.

    METHODS: In the community-based Prospective Investigation of the Vasculature of Uppsala Seniors study (PIVUS, n = 952, mean age 70, women 49.3%), we investigated cross-sectional associations between estimated cystatin C-based glomerular filtration rate (eGFR), and 3 measures representing different aspects of endothelial function (endothelial-dependent vasodilation [EDV], endothelial independent vasodilatation [EIDV], and flow-mediated dilatation [FMD]). We also performed pre-specified sub-group analyses in participants with normal eGFR (>60 ml/min/1.73 m(2)).

    RESULTS: In the whole cohort, 10 ml/min/1.73 m(2) higher eGFR was associated with 3% higher EDV (p = 0.001) and 2% higher EIDV (p = 0.007), adjusted for age and sex. The associations were attenuated and no longer statistically significant after adjusting for established cardiovascular risk factors. In participants with eGFR >60 ml/min/1.73 m(2), 10 ml higher eGFR was associated with 2% higher EDV (p = 0.04) after adjusting for sex and age. eGFR was not associated to FMD in any model or sub-sample.

    CONCLUSION: This community-based study suggests that eGFR is associated with endothelial function also in persons with normal kidney function, but that this association is largely explained by confounding by established cardiovascular risk factors. Thus, our data do not support the notion of a direct causal interplay between renal and vascular function prior to the development of CKD.

  • 409.
    Nerpin, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna-Medicinsk vetenskap.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Andrén, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Jobs, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna Medicinsk vetenskap.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna Medicinsk vetenskap.
    The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly2014Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, nr 11, s. 2069-2074Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) > 40% and with pre-specified sub-group analyses in individuals with a GFR > 60 mL/min/m(2). Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR > 60 mL/min/m(2). Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.

  • 410.
    Nerpin, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jobs, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Jobs, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk virologi.
    Hallan, Stein
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    The combined contribution of albuminuria and glomerular filtration rate to the prediction of cardiovascular mortality in elderly men2011Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, nr 9, s. 2820-2827Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without CVD in the community is scarce.

    METHODS: We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study; n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths).

    RESULTS: Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without CVD at baseline [subsample without CVD: UAER; hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01; eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR < 60 mL/min/1.73m(2)), appeared less suitable for cardiovascular risk prediction [integrated discrimination improvement (IDI) 0.006, P = 0.11], while cutoffs UAER > 6 μg/min and eGFR < 45 mL/min/1.73m(2) significantly improved IDI (0.047, P < 0.001).

    CONCLUSIONS: UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.

  • 411. Nerpin, Elisabet
    et al.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jobs, Magnus
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort2008Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, nr 8, s. 1550-1555Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR. RESEARCH DESIGN AND METHODS: We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. RESULTS: Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69-1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m(2)) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40-0.84]; P < 0.004). CONCLUSIONS: Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.

  • 412.
    Niemelä, Valter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Blennow, Kaj
    Zetterberg, Henrik
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Sundblom, Jimmy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Cerebrospinal fluid sCD27 levels indicate active T cell-mediated inflammation in premanifest Huntington's disease2018Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 13, nr 2, artikkel-id e0193492Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: Huntington's disease (HD) is a neurodegenerative disorder, but evidence also suggests neuroinflammation in the pathogenesis. The immune mechanisms involved and the timing of their activation need further clarification.

    METHODS: A clinically well-characterized HD cohort and gene negative controls were enrolled. YKL-40 reflecting innate immunity and sCD27, a marker of adaptive immunity, were measured across disease stages. Comparisons were made with markers of neurodegeneration: neurofilament light (NFL), total-tau (T-tau), and phospho-tau (P-tau).

    RESULTS: 52 cross-sectional cerebrospinal fluid samples and 23 follow-up samples were analyzed. sCD27 was elevated in manifest HD and premanifest gene expansion carriers, whereas controls mostly had undetectable levels. YKL-40 showed a trend toward increase in manifest HD. sCD27 correlated with YKL-40 which in turn was closely associated to all included markers of neurodegeneration. YKL-40, NFL, and both forms of tau could all independently predict HD symptoms, but only NFL levels differed between groups after age-adjustment.

    CONCLUSION: Increased sCD27 in premanifest HD is a sign of T cell-mediated neuroinflammation. This finding is novel since other reports almost exclusively have found early involvement of innate immunity. Validation of sCD27 in a larger HD cohort is needed. The role of adaptive immunity in HD needs further clarification, as it may hasten disease progression.

    Fulltekst (pdf)
    fulltext
  • 413.
    Nilsen, Tom
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Gentian Technology AS, Moss, Norway.
    Haugen, SH
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Extraction,isolation, and concentration of calprotectin antigen (S100A8/S100A9) fromgranulocytes2018Inngår i: Health Science Reports, E-ISSN 2398-8835, Vol. 1, nr 5, artikkel-id 35Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Calprotectin is a promising biomarker for granulocyte activation. It is mainly measured in faeces as a marker for inflammatory bowel disease. A limitation is that there is no widely accepted calibrator.

    Aim: To establish a method for purification of calprotectin from human granulocytes that is easily reproducible, reliable, and could contribute to a better agreement between different calprotectin methods.

    Methods and results: Calprotectin was purified from granulocyte extracts using ion‐exchange chromatography. The granulocytes were separated from blood bags. The purity was analysed by analysing pixel density of a picture of the sodium dodecyl sulfate polyacrylamide gel electrophoresis and by size exclusion chromatography. The calprotectin concentration of the pure antigen solution was determined using Biuret method. The purity was >95% for 3 preparations, and their concentrations were 1079, 1080, and 1813 mg/L.

    Conclusion: It is possible to reproducibly prepare highly purified calprotectin antigen from human granulocytes. The preparations can be used for preparing calibrators, controls for immunological calprotectin assays, and immunisation for raising antibodies against human calprotectin in hens.

    Fulltekst (pdf)
    fulltext
  • 414.
    Nilsen, Tom
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Gentian AS, Moss, Norway.
    Sunde, Kathrin
    Gentian AS, Moss, Norway.
    Hansson, Lars-Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Mandic Havelka, Aleksandra
    Karolinska Univ Hosp, Karolinska Inst & Clin Chem, Dept Mol Med & Surg, Stockholm, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    A novel turbidimetric immunoassay for fecal calprotectin optimized for routine chemistry analyzers2017Inngår i: Journal of clinical laboratory analysis (Print), ISSN 0887-8013, E-ISSN 1098-2825, Vol. 31, nr 4, artikkel-id e22061Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Fecal calprotectin assays are widely used to exclude inflammatory bowel disease (IBD) in patients with suspected IBD. A problem with the fecal calprotectin assays is the rather long test-turnaround times. A particle enhanced turbidimetric immunoassays (PETIA) for fecal calprotectin would reduce test-turnaround times and would permit more laboratories to perform the measurements. The aim of this study was to evaluate a new feces calprotectin PETIA.

    METHOD: Using routine fecal samples the feces calprotectin PETIA was validated on two chemistry analyzers, Mindray BS-380 and Cobas 501.

    RESULTS: The assay is linear in the range 11-2000 μg/g, with a limit of quantitation of approximately 10 μg/g. No antigen excess hook effect was observed up to 10 000-15 000 μg/g depending on the instrument used. The turbidimetric method showed a good agreement with the Bühlmann ELISA. The total coefficient of variation was 3%-8% in the 50-100 μg/g range.

    CONCLUSION: The fecal calprotectin PETIA, fCal Turbo, is well suited for rapid analysis of fecal calprotectin on Mindray BS-380 or Cobas 501 clinical chemistry analyzers. The test results are commutable with Bühlmann fecal MRP8/14 ELISA.

  • 415.
    Nilsen, Tom
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sunde, Kathrin
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    A new turbidimetric immunoassay for serum calprotectin for fully automatized clinical analysers2015Inngår i: Journal of Inflammation, E-ISSN 1476-9255, Vol. 12, artikkel-id 45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Serum and plasma calprotectin concentration is shown to be elevated when neutrophils are activated, and may therefore be used as a marker for inflammatory diseases. A serum calprotectin immunoassay was developed based on calprotectin values observed in samples from the intensive care unit. The polyclonal avian antibodies were raised and affinity purified with calprotectin antigens. The performance was tested and it was observed that the assay was linear in the range 0.3-24.7 mg/L, the limit of quantitation was observed to be lower than 0.3 mg/L, no antigen excess was observed up to 54 mg/L, all CVs were lower than 1.8 % in the precision study, the calibration curve stability was longer than 6 weeks, and there was no significant interference detected for haemoglobin, intralipid or bilirubin. The serum calprotectin immunoassay presented in this paper performs well within the criteria carefully set from the limited clinical experience obtained in both serum and plasma. In addition it is commutable with Bühlmann MRP8/14 ELISA.

    Fulltekst (pdf)
    fulltext
  • 416.
    Nilsen, Tom
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Serum calprotectin levels in elderly males and females without bacterial or viral infections2014Inngår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, nr 12, s. 1065-1068Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Calprotectin is released from activated leukocytes and calprotectin can thus be used as a marker for leukocyte activation. Faeces calprotectin is not only used as a marker for inflammatory bowel disease but can also be used to detect leukocyte activation in other body fluids. The aim of the present study was to study serum calprotectin levels in non-infected elderly individuals to establish reference intervals for the marker.

    METHODS: Serum calprotectin was analyzed by immunoturbidimetry in 75year old females and males without known infections. Individuals with CRP>20mg/L were excluded as this could indicate a subclinical infection. The calprotectin levels in the remaining 713 individuals were used to calculate reference values for this population. The Spearman rank correlations between calprotectin and 27 other laboratory biomarkers were also investigated.

    RESULTS: There was a strong positive Spearman rank correlation between calprotectin and CRP (p<0.000001) and alkaline phosphatase (p<0.000001). There were also significant negative correlations between calprotectin and ApoA1 and direct HDL-cholesterol.

    CONCLUSIONS: The reference interval for serum-calprotectin for all study subjects was 0.3-2.6mg/L. Leukocyte alkaline phosphatase contributes to serum alkaline phosphatase levels.

  • 417.
    Nilsson, Elin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Amini, Ahmad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Wretlind, Bengt
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin: Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin2007Inngår i: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 856, nr 1-2, s. 75-80Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pseudomonas aeruginosa (PA) is the main cause of morbidity and mortality in cystic fibrosis (CF) patients. CF patients with chronic PA infections have a more rapid deterioration of their lung function and the bacteria become impossible to eradicate from the lungs. Antibiotic resistance among PA strains in CF patients is steadily increasing. Specific chicken (IgY) antibodies against PA have been shown to have potential to prevent PA infections in CF. Anti-Pseudomonas IgY reduces PA adhesion to epithelia, but the mechanism has not been fully elucidated. To gain further insight into the prophylactic effect of these antibodies, the immunoreactivity was investigated by 2D electrophoresis of PA strains, immunoblotting and MALDI-TOF-MS. To confirm the identity of the proteins, the tryptic peptides were analyzed by MALDI-TOF-MS to accurately measure their monoisotopic masses as well as determine their amino acid sequences. In order to facilitate fragmentation of the peptides they were N-terminally or C-terminally labeled. Several strains were investigated and anti-Pseudomonas IgY was immunoreactive against all of these strains, which strengthens its potential as a prophylactic treatment against PA. Flagellin was identified as the major antigen. Flagellin is the main protein of the flagella and is crucial for establishing infections in hosts as well as being involved in PA chemotaxis, motility, adhesion and inflammation. Furthermore, secreted flagellin elicits an inflammatory response. In conclusion, anti-Pseudomonas IgY binds flagellin, which may prevent PA infections in CF patients by hindering host invasion.

  • 418.
    Nilsson, Elin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Bodolea, Constantin
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Cerebrospinal fluid cathepsin B and S2013Inngår i: Neurological Sciences, ISSN 1590-1874, E-ISSN 1590-3478, Vol. 34, nr 4, s. 445-448Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cathepsins are increased in the brain of elderly animals. We investigate the presence of cathepsin B and S in human cerebrospinal fluid (CSF) plasma and the associations with cystatin C, age and sex. We measured cathepsin B and S concentrations in CSFs from 118 persons, undergoing elective surgical procedures, with ELISA. Both cathepsin B and cathepsin S were positively correlated with age. No correlation was observed between cathepsin B or S and length, height or body mass index. Both cathepsin B and S were positively correlated to the cystatin C concentration in CSF. Calculated reference intervals were 4,893–17,636 pg/mL for cathepsin B and 2,681–11,459 pg/mL for cathepsin S. Elderly individuals had significantly higher levels of both cathepsin B (r s = 0.38, p = 0.00002) and cathepsin S (r s = 0.35, p = 0.0001) in CSF.

  • 419.
    Nilsson, Elin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Kollberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Johannesson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Wejåker, Per-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Carlander, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    More than 10 years' continuous oral treatment with specific immunoglobulin Y for the prevention of Pseudomonas aeruginosa infections: a case report2007Inngår i: Journal of Medicinal Food, ISSN 1096-620X, E-ISSN 1557-7600, Vol. 10, nr 2, s. 375-378Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Immunotherapy with specific antibodies is an alternative to antibiotics for the prevention of infections in humans and animals. We have used orally administered immunoglobulin Y (IgY) preparations, purified from eggs of hens immunized with Pseudomonas aeruginosa bacteria, to prevent pulmonary P. aeruginosa infections in a group of patients with cystic fibrosis (CF). Respiratory infections are major problems for CF patients because of the thick mucus in the airways, and chronic P. aeruginosa lung infections occur in virtually all CF patients and cause morbidity and mortality. The IgY-treated group had only 2.5 P. aeruginosa-positive sputum cultures per 100 months, and none of the IgY-treated patients became chronically colonized with P. aeruginosa. In the control group, 13.7 of the cultures per 100 months were positive for P. aeruginosa, and 24% of patients became chronically colonized with P. aeruginosa. The first enrolled patient in this study has now been treated continuously for more than 10 years. During the first 8 years she only had four P. aeruginosa-positive cultures. After 8 years she became chronically infected, but still after 10 years the bacteria have not turned mucoid. No negative side effects of IgY treatment have been noted during these 10 years. To our knowledge this is the longest treatment with specific yolk antibodies for therapeutic purposes.

  • 420.
    Nilsson, Elin
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. klinisk kemi.
    Chicken anti-protein L for the detection of small amounts of protein L in the presence of IgG.2005Inngår i: Hybridoma (Larchmt), ISSN 1554-0014, Vol. 24, nr 2, s. 112-4Artikkel i tidsskrift (Fagfellevurdert)
  • 421.
    Nilsson, Elin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Stability of chicken IgY antibodies freeze-dried in the presence of lactose, sucrose and trehalose2007Inngår i: Journal of Poultry Science, ISSN 1349-0486, Vol. 44, nr 1, s. 58-62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Freeze-drying is used as a method to stabilize proteins. The process itself may however cause protein unfolding and denaturation, but the risk is reduced if a stabilizing agent is added prior to freeze-drying. Here chicken antibody (IgY) preparations were freeze-dried in the presence or absence of lactose, sucrose and threalose as stabilizing agent at 0.3, 0.06 and 0.012M. The activity of freeze-dried IgY batches in the absence of stabilizing agent was similar before and after freeze-drying, but decreased slowly during eight weeks at 37°C. Addition of disaccharide resulted in a preserved activity after eight weeks in 37°C, compared to samples with no sugar added. The results were similar irrespective of sugar type and concentration (0.012-0.3M). This shows that IgY freeze-dried in the presence of disaccharide is very stable and a method to reduce the cost and simplify transport, storage and use of avian antibodies.

  • 422.
    Nilsson, Elin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Olesen, Hanne V.
    Wejåker, Per-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kollberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Good effect of IgY against Pseudomonas aeruginosa infections in cystic fibrosis patients2008Inngår i: Pediatric Pulmonology, ISSN 8755-6863, E-ISSN 1099-0496, Vol. 43, nr 9, s. 892-899Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This is an extended open study of oral prophylactic treatment with egg yolk antibodies against Pseudomonas aeruginosa, Anti-Pseudomonas IgY, of 17 Swedish patients with cystic fibrosis. They have been on prophylactic IgY treatment for up to 12 years and altogether for 114 patient years. A group of 23 Danish CF patients served as control. There has been a total absence of adverse events. Only 29 cultures have been positive for P. aeruginosa (cultures after chronic colonization not included), that is, 2.3/100 treatment months compared to 7.0/100 months in the control group (P = 0.028). In the IgY treated group only one pair of siblings (2/17) has been chronically colonized with P. aeruginosa compared to seven patients (7/23) in the control group. Atypical mycobacteria, S. maltophilia, A. xylosoxidans, and A. fumigatus have appeared only sporadically. There have been no cultures positive for B. cepacia. There was no decrease in pulmonary functions (P = 0.730) within the IgY group. Body mass index values were normal or close to normal for all IgY treated patients. In conclusion, Anti-Pseudomonas IgY has great potential to prevent P. aeruginosa infections.

  • 423.
    Nilsson, Elin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Stålberg, Johan
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    IgY stability in eggs stored at room temperature or at +4°C2012Inngår i: British Poultry Science, ISSN 0007-1668, E-ISSN 1466-1799, Vol. 53, nr 1, s. 42-46Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    1. The aim of this study was to investigate the stability of immunoglobulin-Y (IgY) in stored eggs from immunised hens.

    2. Eggs from individual hens were randomised and stored for up to one month at room temperature, or for up to 6 months at +4°C. IgY was extracted from the egg yolks and the antibody activities were tested by ELISA.

    3. There was no significant reduction in antibody titres with egg storage under these conditions.

    4. Egg yolks of immunised chickens provide an inexpensive source of large amounts of polyclonal antibodies for use in immunotherapy and immunoassays. By collecting eggs from different immunised hens and pooling their yolks, it should be possible to reduce batch-to-batch variation.

  • 424.
    Nilsson, Erik
    et al.
    School of Medical Sciences, Örebro University, 70182 Örebro, Sweden..
    Kastrup, Jens
    Department of Cardiology, Rigshospitalet University of Copenhagen, 2100 Copenhagen, Denmark..
    Sajadieh, Ahmad
    Department of Cardiology, Copenhagen University Hospital of Bispebjerg and Frederiksberg, 2000 Frederiksberg, Denmark..
    Boje Jensen, Gorm
    Department of Cardiology, Hvidovre Hospital University of Copenhagen, 2650 Hvidovre, Denmark..
    Kjøller, Erik
    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark..
    Kolmos, Hans Jørn
    Department of Clinical Microbiology, Odense University Hospital, 5000 Odense, Denmark..
    Wuopio, Jonas
    Department of Medicine, Mora County Hospital, 79251 Mora, Sweden..
    Nowak, Christoph
    Division for Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 14183 Huddinge, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Jakobsen, Janus Christian
    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark..
    Winkel, Per
    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark..
    Gluud, Christian
    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark..
    Iversen, Kasper K
    Department of Cardiology S, Herlev Hospital University of Copenhagen, 2730 Herlev, Denmark..
    Ärnlöv, Johan
    Division for Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 14183 Huddinge, Sweden..
    Carlsson, Axel C.
    Division for Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 14183 Huddinge, Sweden..
    Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up: A CLARICOR Trial Sub-Study2020Inngår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, nr 1, artikkel-id 265Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Elevated pregnancy-associated plasma protein A (PAPP-A) is associated with mortality in acute coronary syndromes. Few studies have assessed PAPP-A in stable coronary artery disease (CAD) and results are conflicting. We assessed the 10-year prognostic relevance of PAPP-A levels in stable CAD. The CLARICOR trial was a randomized controlled clinical trial including outpatients with stable CAD, randomized to clarithromycin versus placebo. The placebo group constituted our discovery cohort (n = 1.996) and the clarithromycin group the replication cohort (n = 1.975). The composite primary outcome was first occurrence of cardiovascular event or death. In the discovery cohort, incidence rates (IR) for the composite outcome were higher in those with elevated PAPP-A (IR 12.72, 95% Confidence Interval (CI) 11.0-14.7 events/100 years) compared to lower PAPP-A (IR 8.78, 8.25-9.34), with comparable results in the replication cohort. Elevated PAPP-A was associated with increased risk of the composite outcome in both cohorts (discovery Hazard Ratio (HR) 1.45, 95% CI 1.24-1.70; replication HR 1.29, 95% CI 1.10-1.52). In models adjusted for established risk factors, these trends were attenuated. Elevated PAPP-A was associated with higher all-cause mortality in both cohorts. We conclude that elevated PAPP-A levels are associated with increased long-term mortality in stable CAD, but do not improve long-term prediction of death or cardiovascular events when added to established predictors.

    Fulltekst (pdf)
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  • 425. Nitsch, Dorothea
    et al.
    Grams, Morgan
    Sang, Yingying
    Black, Corri
    Cirillo, Massimo
    Djurdjev, Ognjenka
    Iseki, Kunitoshi
    Jassal, Simerjot K
    Kimm, Heejin
    Kronenberg, Florian
    Oien, Cecilia M
    Levey, Andrew S
    Levin, Adeera
    Woodward, Mark
    Hemmelgarn, Brenda R
    Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis2013Inngår i: The BMJ, E-ISSN 1756-1833, Vol. 346, s. f324-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease.

    DESIGN: Random effects meta-analysis using pooled individual participant data.

    SETTING: 46 cohorts from Europe, North and South America, Asia, and Australasia.

    PARTICIPANTS: 2,051,158 participants (54% women) from general population cohorts (n=1,861,052), high risk cohorts (n=151,494), and chronic kidney disease cohorts (n=38,612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥ 50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m(2)) and urinary albumin-creatinine ratio (mg/g).

    RESULTS: Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (P(interaction)<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (P(interaction)<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk.

    CONCLUSIONS: Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.

  • 426.
    Noraddin, Feria Hikmet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Flodin, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Fredricsson, Annika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sohrabian, Azita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Measurement of urinary cystatin C with a particle-enhanced turbidimetric immunoassay on architect ci82002012Inngår i: Journal of clinical laboratory analysis (Print), ISSN 0887-8013, E-ISSN 1098-2825, Vol. 26, nr 5, s. 358-364Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Cystatin C is a low-molecular-weight protein that is freely filtered by the glomerulus and catabolized after reabsorption by the proximal tubular cells in healthy subjects. Urinary cystatin C is a potential biomarker for tubular damage including acute kidney injury (AKI) in the acute phase when patients are submitted to the intensive care unit.

    METHODS:

    The aim of this study was to perform a method validation of urinary analysis of cystatin C by particle-enhanced turbidimetric immunoassay (PETIA) on a high-throughput chemical analyzer. Total assay time was 10 min. The antigen excess, linearity, lower limit of quantification (LoQ), recovery, assay precision, stability, and interference caused by hemoglobin were evaluated.

    RESULTS:

    The LoQ was calculated to 0.020 mg/l with a coefficient of variation (CV) ≤ 10%. No hook effect was observed and the assay was linear over the studied interval less than 0.020-0.950 mg/l with a regression of R(2) = 0.9994. The assay had a recovery between 93-100% and the assay precision had a total CV of less than 3.5%. Cystatin C was stable for 3 days in room temperature and 14 days in +4C. The assay did not show any major interference with hemoglobin at a hemoglobin concentration of 10 g/L. The reference interval for urine cystatin C was less than 0.166 mg/l.

    CONCLUSION:

    The urinary cystatin C PETIA showed good precision and performance characteristics including short test turnaround times that are necessary qualifications for a biomarker at a routine laboratory.

  • 427. Nordin, A
    et al.
    Björnådal, L
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Svenungsson, E
    Jensen-Urstad, K
    Electrocardiography in 110 patients with systemic sclerosis: a cross-sectional comparison with population-based controls2014Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr 3, s. 221-225Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives:

    Patchy fibrosis of the myocardium is thought to cause conduction abnormalities in patients with systemic sclerosis (SSc). We compared the prevalence and type of rhythm/conduction disturbances in 74% of the SSc patients in Stockholm County and controls.

    Method: A total of 110 SSc patients (age 62 ± 12 years) fulfilling the American College of Rheumatology (ACR) criteria for SSc and 105 gender- and age-matched controls participated in this study. A 12-lead resting electrocardiogram (ECG) was performed in all participants. The first 49 patients and 42 controls also underwent a 22-24-h Holter ECG recording. Associations with disease subsets, autoantibodies, cardiovascular risk factors, and left ventricular ejection fraction (LVEF), as estimated by echocardiography, were investigated.

    Results:

    Abnormal ECGs were found in 28% of patients and 17% of controls (p = 0.05). Atrioventricular (AV) and/or intraventricular (IV) conduction abnormalities were found in 15% of patients and 5% of controls (p < 0.01). Four patients, but no controls, had low anteroseptal R-wave/septal Q-wave patterns with narrow QRS complexes, simulating a septal wall infarction pattern. Patients had more abnormal Holter ECG recordings than controls (38% vs. 17%, p = 0.05). All participants with a normal resting ECG had an LVEF ≥ 50%.

    Conclusions:

    Although ECGs are inexpensive, commonly available screening tools, to detect arrhythmias, such as frequent ventricular extrasystoles (VES), Holter tracings should be performed. The frequencies of AV and/or IV conduction abnormalities and septal Q waves/low R waves have not changed since 1985. The unmet need of anti-fibrotic treatment in SSc is underscored by these findings.

  • 428.
    Nordin, Gunnar
    et al.
    Equalis, Uppsala, Sweden.
    Ekvall, Sara
    Equalis, Uppsala, Sweden.
    Kristoffersson, Carolina
    Equalis, Uppsala, Sweden.
    Jonsson, Ann-Sofie
    Landstinget Varmland, Dept Clin Chem, Karlstad, Sweden.
    Bäck, Sten-Erik
    Lund Univ Hosp, Dept Clin Chem, Lund, Sweden.
    Rollborn, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Accuracy of determination of the glomerular filtration marker iohexol by European laboratories as monitored by external quality assessment2019Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 57, nr 7, s. 1006-1011Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Glomerular filtration is the most important kidney function. The most accurate glomerular filtration rate (GFR) estimates are based on the clearance of exogenous filtration markers. Of these, iohexol is the only exogenous marker that is included in an external quality assessment (EQA) scheme. The aim of the present study was to evaluate the performance of the European laboratories participating in Equalis' EQA scheme for iohexol. Methods Weighed amounts of iohexol (Omnipaque) were added to plasma samples and distributed to laboratories participating in the EQA scheme for iohexol. All laboratories performed the assays in a blinded fashion. Results The number of participating laboratories varied between 27 and 34 during the study period. Iohexol was determined by HPLC in 77% of the laboratories and by UPLC/MS/MS methods in 15% of the laboratories. The mean interlaboratory coefficient of variation was 4.7% for the HPLC methods and 6.4% for the UPLC/MS/MS methods. The mean bias between calculated and measured iohexol values was -1.3 mg/L (95% confidence interval ±0.3) during the first part of the study period and 0.1 mg/L (±0.3) during the later part. Conclusions The low interlaboratory variation demonstrates that iohexol can be measured reliably by many laboratories and supports the use of iohexol as a GFR marker when there is a need for high quality GFR measurements.

  • 429.
    Nordmark, Gunnel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Bengtsson, Christine
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sturfelt, Gunnar
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Effects of Dehydroepiandrosterone Supplement on Health-related Quality of Life in Glucocorticoid Treated Female Patients with Systemic Lupus Erythematosus2005Inngår i: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 38, nr 7, s. 531-540Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of this study was to evaluate the efficacy of low dose dehydroepiandrosterone (DHEA) on health-related quality of life (HRQOL) in glucocorticoid treated female patients with systemic lupus erythematosus (SLE). Forty one women ( >or= 5 mg prednisolone/day) were included in a double-blind, randomized, placebo-controlled study for 6 months where DHEA was given at 30 mg/20 mg ( or= 46 years) daily, or placebo, followed by 6 months open DHEA treatment to all patients. HRQOL was assessed at baseline, 6 and 12 months, using four validated questionnaires and the patients' partners completed a questionnaire assessing mood and behaviour at 6 months. DHEA treatment increased serum levels of sulphated DHEA from subnormal to normal. The DHEA group improved in SF-36 "role emotional" and HSCL-56 total score (both p<0.05). During open DHEA treatment, the former placebo group improved in SF-36 "mental health" (p<0.05) with a tendency for improvement in HSCL-56 total score (p=0.10). Both groups improved in McCoy's Sex Scale during active treatment (p<0.05). DHEA replacement decreased high-density lipoprotein (HDL) cholesterol and increased insulin-like growth factor I (IGF-I) and haematocrit. There were no effects on bone density or disease activity and no serious adverse events. Side effects were mild. We conclude that low dose DHEA treatment improves HRQOL with regard to mental well-being and sexuality and can be offered to women with SLE where mental distress and/or impaired sexuality constitutes a problem.

  • 430.
    Norrgrann, Moa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Hörnfeldt, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Latheef, Faiza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Thernström Blomqvist, Ylva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Paulsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Diderholm, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Lipid Peroxidation and Antioxidative Capacity Are Unaltered in Transitional Breast Milk Exposed to Light from Women Giving Birth to Preterm Infants before 32 Weeks of Gestation2023Inngår i: Nutrients, E-ISSN 2072-6643, Vol. 15, nr 12, artikkel-id 2818Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Breast milk (BM) is the primary nutrition for infants and has a high content of lipids. Preterm infants receive expressed BM via tube feeding, and they are frequently treated with phototherapy. When parenteral nutrition (PN) is exposed to light and/or phototherapy, lipid peroxidation (LPO) increases. By light-protecting PN, morbidity and mortality are reduced in preterm infants through the reduction of oxidative stress. We aimed to investigate whether light-protecting breast milk could reduce LPO. Twelve mothers giving birth to a preterm infants of less than 32 weeks of gestational age were included. Transitional BM was collected and divided into three study groups; light-protected, ward light and phototherapy light. Baseline samples were collected after expression and the exposures started within one hour. Feeding syringe samples were exposed to light for 30 up to 360 min. Nasogastric tube samples were run through a tube under the same light conditions. Samples were stored in -80 °C until analyses of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) and total antioxidant capacity (TAC). There were no significant differences in MDA, 4-HNE or TAC levels observed between the different study groups. This study indicates that the light exposure of expressed transitional BM does not affect LPO and the levels of MDA, 4-HNE or TAC.

    Fulltekst (pdf)
    fulltext
  • 431.
    Nyberg, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Gremo, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Blixt, Jonas
    Karolinska Univ Hosp, Perioperat Med & Intens Care PMI, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol FyFa, Stockholm, Sweden..
    Sperber, Jesper
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Pikwer, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin. Perioperative Medicine and Intensive Care (PMI), Karolinska University Hospital, Stockholm, Sweden.;The Department of Physiology and Pharmacology (FyFa), Karolinska Institute, Stockholm, Sweden.;Department of Anaesthesiology & Intensive Care, Centre for Clinical Research, Sörmland, Mälarsjukhuset, 631 88, Eskilstuna, Sweden..
    Lung-protective ventilation increases cerebral metabolism and non-inflammatory brain injury in porcine experimental sepsis2021Inngår i: BMC Neuroscience, E-ISSN 1471-2202, Vol. 22, artikkel-id 31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. In sepsis-induced encephalopathy or acute brain injury the use of protective ventilation has not been widely investigated (experimentally or clinically). We hypothesized that protective ventilation would attenuate cerebral inflammation in a porcine endotoxemic sepsis model. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Nine animals received protective mechanical ventilation with a tidal volume of 6 mL × kg-1 and nine animals were ventilated with a tidal volume of 10 mL × kg-1. During a 6-h experiment, the pigs received an endotoxin intravenous infusion of 0.25 µg × kg-1 × h-1. Systemic, superior sagittal sinus and jugular vein blood samples were analysed for inflammatory cytokines and S100B. Intracranial pressure, brain tissue oxygenation and brain microdialysis were sampled every hour.

    RESULTS: No differences in systemic or sagittal sinus levels of TNF-α or IL-6 were seen between the groups. The low tidal volume group had increased cerebral blood flow (p < 0.001) and cerebral oxygen delivery (p < 0.001), lower cerebral vascular resistance (p < 0.05), higher cerebral metabolic rate (p < 0.05) along with higher cerebral glucose consumption (p < 0.05) and lactate production (p < 0.05). Moreover, low tidal volume ventilation increased the levels of glutamate (p < 0.01), glycerol (p < 0.05) and showed a trend towards higher lactate to pyruvate ratio (p = 0.08) in cerebral microdialysate as well as higher levels of S-100B (p < 0.05) in jugular venous plasma compared with medium-high tidal volume ventilation.

    CONCLUSIONS: Contrary to the hypothesis, protective ventilation did not affect inflammatory cytokines. The low tidal volume group had increased cerebral blood flow, cerebral oxygen delivery and cerebral metabolism together with increased levels of markers of brain injury compared with medium-high tidal volume ventilation.

    Fulltekst (pdf)
    fulltext
  • 432.
    Nyberg, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Sperber, Jesper
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Endotoxemia versus pneumonia or lung-protective ventilation decelerates the decrease in plasma myostatin levels in a porcine intensive care modelManuskript (preprint) (Annet vitenskapelig)
  • 433. Nylander, Martina
    et al.
    Osman, Abdimajid
    Ramström, Sofia
    Aklint, Emma
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lindahl, Tomas L
    The role of thrombin receptors PAR1 and PAR4 for PAI-1 storage, synthesis and secretion by human platelets2012Inngår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 129, nr 4, s. e51-e58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION:

    Arterial thrombi contain more platelets than venous thrombi and are more resistant to fibrinolysis. This resistance could partly be due to plasminogen activator inhibitor 1 (PAI-1) secreted by platelets. The aim of this study was to elucidate differences between thrombin receptors protease-activated receptor (PAR) 1 and 4 and platelet storage, secretion and synthesis of platelet PAI-1, as compared to other platelet α-granule proteins such as VEGF and endostatin.

    MATERIALS AND METHODS:

    Human isolated platelets were incubated with thrombin (0.5U/ml), PAR1-activating peptide (AP) (0.4-30μM) or PAR4-AP (1.5-300μM) for up to 24hours. ELISA, western blot and fluorescence microscopy were used to measure secretion, contents and localization of PAI-1, VEGF and endostatin.

    RESULTS:

    Our results show that PAI-1 and VEGF might be co-localized and that endostatin does not co-localize with either PAI-1 or VEGF. PAI-1 and VEGF show a similar secretion pattern, being more sensitive to low grade PAR1 activation, but secretion was also observed with higher concentrations of PAR4-APs. PAI-1 is secreted in an active form. PAI-1 mRNA was found in platelets, and elevated levels of PAI-1 were detected after 24hours incubation of platelets.

    CONCLUSIONS:

    PAI-1 and VEGF, but not endostatin, might be stored in the same α-granule in human platelets. PAI-1 and VEGF also show a similar secretion pattern, being more sensitive to PAR1 than to PAR4 activation, but the secretion is not exclusively selective. Our results also show that platelet PAI-1 is increased if incubated for 24hours, both with addition of PAR1-activating peptide and without activation, which could indicate de novo synthesis.

  • 434.
    Nylander, Ruta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Relation between Cardiovascular Disease Risk Markers and Brain Infarcts Detected by Magnetic Resonance Imaging in an Elderly Population2015Inngår i: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 24, nr 2, s. 312-318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75.

    METHODS:

    Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnaires at age 70 were used for analysis of risk markers. A history of diseases had been obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models.

    RESULTS:

    One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts.

    CONCLUSIONS:

    The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown recently.

  • 435.
    Nyman, Ulf
    et al.
    institutionen för trans-lationell medicin, divisionen för medicinsk radiologi, Lunds universitet, Malmö.
    Berg, Ulla
    enheten för pediatrik, CLINTEC, Karolinska institutet; sektionen för barnnefrologi, Astrid Lindgrens barnsjukhus, Stockholm.
    Grubb, Anders
    institutionen för laboratoriemedicin, avdelningen för klinisk kemi och farmakologi, Lunds universitet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Hansson, Magnus
    klinisk kemi, Karolinska universitetslaboratoriet, Stockholm.
    Littmann, Karin
    ME endokrinologi, Karolinska universitetssjukhuset; institutionen för medicin Huddinge, Karolinska institutet, Stockholm.
    Åsling-Monemi, Kajsa
    enheten för pediatrik, CLINTEC, Karolinska institutet; Astrid Lindgrens barnsjukhus, Stockholm.
    Björk, Jonas
    institutionen för laboratoriemedicin, Lunds universitet.
    [GFR estimation in children - age-adjusted creatinine makes the adult Lund-Malmö equation applicable in children and facilitates automatic GFR reporting from the clinical laboratory]2021Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 118, artikkel-id 20134Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Age-adjustment of creatinine, i.e. recalculation of childhood levels of creatinine to corresponding levels at 18 years of age and applied in the adult revised Lund-Malmö GFR equation led to markedly improved accuracy in Swedish children (n=1 718) at measured GFR <75 mL/min/1.73 m2 (n=318) and preserved high accuracy at ≥75 mL/min/1.73 m2 (n=1 400). The adjusted LMR equation performed as well as dedicated paediatric equations based on height. The proposed adjustment strategy has four strengths: (i) the original coefficients of the adult GFR equation can be used, (ii) the same equation can be used across the entire lifespan without artificial changes in estimated GFR when switching from paediatric to adult care, (iii) the lack of height factor makes it easier to automatically report estimated GFR by the laboratories and (iv) age-adjusted creatinine values imply that well-established creatinine reference intervals for adults can also be used for children.

  • 436.
    Nyman, Ulf
    et al.
    Department of Translational Medicine, Division of Medical Radiology, Lund University, Malmö, Sweden. .
    Björk, Jonas
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden; Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden..
    Berg, Ulla
    Department of Clinical Science, Intervention and Technology, Division of Paediatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Bökenkamp, Arend
    Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands..
    Dubourg, Laurence
    Néphrologie, Dialyse, Hypertension et Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, and Laboratory of Tissue Biology and Therapeutic Engineering, UMR 5305 CNRS, Université Claude Bernard Lyon 1, Lyon, France..
    Goffin, Karolien
    Department of Nuclear Medicine, University Hospital Leuven, Division of Nuclear Medicine and Molecular Imaging, KU Leuven, Leuven, Belgium..
    Grubb, Anders
    Department of Clinical Chemistry, Skåne University Hospital, Lund University, Lund, Sweden..
    Hansson, Magnus
    Function area Clinical Chemistry, Karolinska University Laboratory, Karolinska University Hospital Huddinge and Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Littmann, Karin
    Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden and Medical Unit of Endocrinology, Theme Inflammation and Ageing, Karolinska University Hospital, Stockholm, Sweden..
    Åsling-Monemi, Kajsa
    Department of Clinical Science, Intervention and Technology, Division of Paediatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Pottel, Hans
    Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium..
    Delanaye, Pierre
    Department of Nephrology-Dialysis-Transplantation, University of Liège (ULg CHU), CHU Sart Tilman, Liège, Belgium; Department of Nephrology-Dialysis-Apheresis, Hopital Universitaire Caremeau, Nimes, France..
    The Modified CKiD Study Estimated GFR Equations for Children and Young Adults Under 25 Years of Age: Performance in a European Multicenter Cohort2022Inngår i: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 80, nr 6, s. 807-810Artikkel i tidsskrift (Fagfellevurdert)
  • 437. Nyman, Ulf
    et al.
    Grubb, Anders
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Hansson, Lars-Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Flodin, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Nordin, Gunnar
    Equalis, Uppsala, Sweden.
    Lindström, Veronica
    Björk, Jonas
    The revised Lund-Malmö GFR estimating equation outperforms MDRD and CKD-EPI across GFR, age and BMI intervals in a large Swedish population2014Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 52, nr 6, s. 815-824Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

     Background:

    The performance of creatinine-based glomerular filtration rate (GFR) estimating equations may vary in subgroups defined by GFR, age and body mass index (BMI). This study compares the performance of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with the revised Lund-Malmö equation (LM Revised), a new equation that can be expected to handle changes in GFR across the life span more accurately.

    Methods:

    The study included 3495 examinations in 2847 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 52 mL/min/1.73 m2). Bias, precision [interquartile range (IQR)] and accuracy [percentage of estimates ±10% (P10) and ±30% (P30) of mGFR] were compared.

    Results:

    The overall results of LM Revised/MDRD/CKD-EPI were: median bias 2%/8%/11%, IQR 12/14/14 mL/min/1.73 m2, P10 40%/35%/35% and P30 84%/75%/76%. LM Revised was the most stable equation in terms of bias, precision and accuracy across mGFR, age and BMI intervals irrespective of gender. MDRD and CKD-EPI overestimated mGFR in patients with decreased kidney function, young adults and elderly. All three equations overestimated mGFR and had low accuracy in patients with BMI <20 kg/m2, most pronounced among men.

    Conclusions:

    In settings similar to the investigated cohort LM Revised should be preferred to MDRD and CKD-EPI due to its higher accuracy and more stable performance across GFR, age and BMI intervals.

  • 438.
    Ognissanti, Damiano
    et al.
    Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden..
    Andresen Bergström, Moa
    Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden..
    Theodorsson, Elvar
    Division of Clinical Chemistry, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Nordin, Gunnar
    External Quality Assurance in Laboratory Medicine in Sweden (EQUALIS), Uppsala, Sweden..
    Hammarsten, Ola
    Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden..
    Estimating Analytical Errors of Glomerular Filtration Rate Measurement.2022Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 68, nr 9, s. 1211-1218, artikkel-id hvac098Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Few studies are available on how to optimize time points for sampling and how to estimate effects of analytical uncertainty when glomerular filtration rate (GFR) is calculated.

    METHODS: We explored the underlying regression mathematics of how analytical variation of a kidney filtration marker affects 1-compartment, slope-and-intercept GFR calculations, using 2 or 3 time points following a bolus injection, and used this to examine the results from 731 routine 3-point iohexol plasma clearance measurements.

    RESULTS: GFR calculations inflated analytical uncertainty if the time points were taken too late after the bolus injection and too close after each other. The uncertainty in GFR calculation was, however, the same as the analytical uncertainty if optimal time points were used. The middle of the 3 samples was of little value. The first sample should be taken as early as possible after the distribution phase. Sampling before the patient specific half-life of the kidney filtration marker resulted in an exponential error inflation whereas no error inflation was seen when sampling occurred later than 2 half-lives. Theoretical GFR uncertainty could be lowered 2.6-fold if individually optimized time points for sampling had been used in our 731 clearance measurements. Using Taylor expansions to approximate the moments of transformed random variables, the uncertainty of an individual GFR measurement could be calculated in a simple enough way to be applicable by laboratory software.

    CONCLUSIONS: We provide a theoretical foundation to select patient-optimal time points that may both limit errors and allow calculation of GFR uncertainty.

    Fulltekst (pdf)
    fulltext
  • 439.
    Oke, V.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Brauner, S.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gustafsson, J.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Zickert, A.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gunnarsson, I.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, E.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Increased Serum Levels Of IFN-Lambda 1 Correlate With TH17 Axis Cytokines And Independently To IFN-Alpha Identify Patient Group With Higher Organ Damage2016Inngår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 34, nr 4, s. S45-S45Artikkel i tidsskrift (Fagfellevurdert)
  • 440.
    Oke, V.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Brauner, S.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Gustafsson, J.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Zickert, A.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gunnarsson, I.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, E.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Increased Serum Levels of IFN-Λ Correlate with Th17 Axis Cytokines and Independently To IFN-α Identify Patient Group with Higher Organ Damage2016Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, s. 128-128Artikkel i tidsskrift (Annet vitenskapelig)
  • 441.
    Oke, Vilija
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Brauner, Susanna
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Gustafsson, Johanna
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Zickert, Agneta
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    IFN-λ1 with Th17 axis cytokines and IFN-α define different subsets in systemic lupus erythematosus (SLE).2017Inngår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, artikkel-id 139Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Interferon (IFN)-α is thought to have a pivotal role in systemic lupus erythematosus (SLE), and type III IFNs (IFN-λ) were recently also associated with SLE. In this study, we measured levels of IFN-α, IFN-λ1, and related cytokines, such as IL-17A, IL-23, and interferon-γ-induced protein 10 (IP-10), in a Karolinska University Hospital cohort of patients with SLE and control subjects. The objective of the study was to investigate if cytokine measurements could identify different subsets of patients with active SLE and higher disease damage.

    METHODS: We included 261 patients with SLE and 261 population control subjects. All participants underwent a standardized clinical examination. Medical files were reviewed. Patients with SLE were assessed for current organ manifestations, disease activity, and damage. Routine blood parameters, complement levels, and serology were analyzed at the time of inclusion. Levels of IFN-λ1, IFN-α, IL-17A, IL-23, and IP-10 were measured by enzyme-linked immunosorbent assay.

    RESULTS: IFN-λ1 and IFN-α were detected in 29% and 44% of patients, respectively, but their levels did not correlate. High serum levels of IFN-λ1 were positively associated with antinucleosome antibodies and lymphopenia but negatively with musculoskeletal damage. Positive correlations between levels of IFN-λ1, IL-17A, and IL-23 were observed. Patients with high levels of these three cytokines had more disease damage, especially renal impairment. High levels of IFN-α were associated with mucocutaneous disease; leukopenia; and low complement, Ro/SSA, and La/SSB. Vascular events and antiphospholipid antibodies were uncommon. We identified two subgroups with high disease activity: one with double-high IFN-λ1 and IFN-α and another with IP-10(high). The former had more neuropsychiatric manifestations, and the latter had more arthritis. Increased levels of both types I and III IFNs were found in a proportion of population control subjects. Therefore, high IFN levels do not seem to be SLE-specific biomarkers.

    CONCLUSIONS: Measurements of circulating IFN-λ1 and IFN-α define subsets of patients with SLE with different characteristics. Levels of IFN-λ1 correlate with T-helper type 17 cytokines and identify a subgroup with more damage. High disease activity is associated with either simultaneous upregulation of IFN-λ1 and IFN-α or independently with IP-10. Our findings could be of major importance when tailoring therapy for patients with SLE with agents targeting IFN pathways.

    Fulltekst (pdf)
    fulltext
  • 442.
    Olausson, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Peterson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Bergström, Mats
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Evaluation of the Meritas® BNP Test for Point-of-Care Testing2015Inngår i: Clinical Laboratory, ISSN 1433-6510, Vol. 61, nr 7, s. 727-730Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: BNP and NT-proBNP are widely used as rule-out tests for heart failure (HF) and they are frequently requested by primary care doctors. A point-of-care (POC) test would reduce the time to diagnosis for patients with suspected HF. The aim of the study was to evaluate a POC BNP test.

    METHODS: Plasma BNP results obtained with the Meritas® POC instrument (n = 82) were compared with the corresponding plasma BNP results analyzed on an Advia Centaur analyzer (Siemens Healthcare, Erlangen, Germany).

    RESULTS: The two methods showed concordant results with a Passing-Bablok correlation between the two methods: BNP(Meritas) = 1.00 x BNP(Siemens) + 1.09; r = 0.9773.

    CONCLUSIONS: The study show that the Meritas® BNP assay could be used in primary care permitting rapid BNP testing to rule out heart failure.

  • 443.
    Olausson, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Petterson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Bergström, Mats
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Evaluation of the Meritas® BNP Test for Point-of-Care Testing2015Inngår i: Clinical Laboratory, ISSN 1433-6510, Vol. 61, nr 7, s. 727-730Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: BNP and NT-proBNP are widely used as rule-out tests for heart failure (HF) and they are frequently requested by primary care doctors. A point-of-care (POC) test would reduce the time to diagnosis for patients with suspected HF. The aim of the study was to evaluate a POC BNP test.

    Methods: Plasma BNP results obtained with the Meritas® POC instrument (n = 82) were compared with the corresponding plasma BNP results analyzed on an Advia Centaur analyzer (Siemens Healthcare, Erlangen, Germany).

    Results: The two methods showed concordant results with a Passing-Bablok correlation between the two methods: BNPMeritas = 1.00 x BNPSiemens + 1.09; r = 0.9773.

    Conclusions: The study show that the Meritas® BNP assay could be used in primary care permitting rapid BNP testing to rule out heart failure.

  • 444. Olofsson, P
    et al.
    Nordquist, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Vingsbo-Lundberg, C
    Larsson, Anders
    University Hospital, Uppsala, Sweden.
    Falkenberg, C
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Akerstrom, B
    Holmdahl, R
    Genetic links between the acute-phase response and arthritis developmentin rats2002Inngår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 46, nr 1, s. 259-268Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    The acute-phase inflammatory response is closely correlated with the development of rheumatoid arthritis, but the pathophysiologic role of its specific components is largely unknown. We investigated the genetic control of the acute-phase protein response in pristane-induced arthritis (PIA), which is a chronic erosive arthritis model in rats.

    METHODS:

    Plasma levels of the acute-phase proteins interleukin-6 (IL-6), alpha1-acid glycoprotein (orosomucoid), fibrinogen, and alpha1-inhibitor3 were quantified in 3 strains of rats during the development and progression of disease: DA and LEW.1F, which are susceptible to arthritis, and E3, which is resistant. Genetic linkage analysis was performed on an F2 intercross between E3 and DA to determine the genetic control of the acute-phase response in arthritis. Elevated levels of alpha1-acid glycoprotein were associated with acute inflammation, whereas levels of IL-6 were increased during the entire course of the disease.

    RESULTS:

    Using these acute-phase markers as quantitative traits in linkage analysis revealed a colocalization of loci controlling the acute-phase response and regions previously shown to control the development of arthritis in chromosomes 10, 12, and 14. In addition, 2 loci that were not associated with arthritis were found to regulate serum levels of the acute-phase protein Apr1 (acute-phase response 1) at the telomeric end of chromosome 12 and Apr2 on chromosome 5.

    CONCLUSION:

    The PIA model in rats is a useful tool for understanding some of the pathways leading to chronic erosive arthritis. The analysis of acute-phase proteins in PIA and its application as quantitative traits for studying the genetics of arthritis will promote the understanding of the genetic regulation of the acute-phase response.

  • 445.
    Olovsson, Matts
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för anatomi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Biotin labelling of chicken antibodies and their subsequent use in ELISA and immunohistochemistry1993Inngår i: Comparative Immunology, Microbiology & Infectious Diseases, ISSN 0147-9571, E-ISSN 1878-1667, Vol. 16, nr 2, s. 145-152Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Avian antibodies have many advantages to mammalian antibodies due to the phylogenetic differences between birds and mammals, resulting in an increased sensitivity and a decreased background in many immunological assays. Since the avidin-biotin system is an efficient detection system for antibodies with a high sensitivity, we wanted to investigate the activity and unspecific binding of optimally biotin labelled chicken antibodies in ELISA and immunohistochemistry. We report on the conditions for biotinylation of chicken antibodies and that optimally biotinylated antibodies show a high activity and a low background in both ELISA and immunohistochemistry.

  • 446.
    Olsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Norlund, Fredrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Pingel, Ronnie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Burell, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Gulliksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Svärdsudd, K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Held, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    The effect of group-based cognitive behavioral therapy on inflammatory biomarkers in patients with coronary disease: results from the SUPRIM-trial2018Inngår i: Upsala Journal of Medical Sciences, Supplement, ISSN 0300-9726, Vol. 123, nr 3, s. 167-173Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The Secondary Prevention in Uppsala Primary Healthcare Project (SUPRIM) is a prospective randomized controlled trial of a group-based cognitive behavioral therapy (CBT) stress management program for coronary heart disease (CHD) patients. The intervention reduced the risk of fatal or non-fatal first recurrent cardiovascular (CV) events. The aim of the present study was to analyze if the positive effects of the CBT program on clinical outcomes could have been mediated by changes in biomarkers for inflammation.

    Methods: Altogether 362 patients with CHD were randomly assigned to intervention or usual care. The inflammatory biomarkers (VCAM-1, TNF-R1, TNF-R2, PTX3, and hs-CRP) were serially assessed at five time points every six months from study start until 24 months later, and analyzed with linear mixed models.

    Results: Baseline levels of the inflammatory markers were near normal, indicating a stable phase. The group-based CBT stress management program did not significantly affect the levels of inflammatory biomarkers in patients with CHD. Three out of five (VCAM-1, TNF-R2, and PTX3) inflammatory biomarkers showed a slight increase over time in both study groups, and all were positively associated with age.

    Conclusion: Group-based CBT stress management did not affect biomarkers for inflammation in patients with CHD. It is therefore unlikely that inflammatory processes including these biomarkers were mediating the effect the CBT program had on the reduction in CV events. The close to normal baseline levels of the biomarkers and the lack of elevated psychological distress symptoms indicate a possible floor effect which may have influenced the results.

    Keywords: Biomarkers, CBT, CHD, inflammation, stress management

    Fulltekst (pdf)
    fulltext
  • 447.
    Olsson, Karl Wilhelm
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Perinatal, neonatal och barnkardiologisk forskning.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Jonzon, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Perinatal, neonatal och barnkardiologisk forskning.
    Sindelar, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Perinatal, neonatal och barnkardiologisk forskning.
    Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22–27 weeks’ gestation2019Inngår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 86, s. 333-338Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Early identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants.

    Methods

    Infants born at 22–27 weeks’ gestation were included in this prospective study. Blood samples were collected on the second day of life. Fourteen biochemical markers associated with factors that may affect PDA closure were analyzed and related to persistent PDA and to the response of pharmacological treatment with ibuprofen.

    Results

    High levels of B-type natriuretic peptide, interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte chemotactic protein 1 were associated with persistent PDA, as were low levels of platelet-derived growth factor. High levels of erythropoietin were associated with both persistent PDA and failure to close PDA within 24 h of the last dose of ibuprofen.

    Conclusions

    High levels of inflammatory markers were associated with the persistence of PDA. High levels of erythropoietin were associated with both the persistence of PDA and failure to respond to pharmacological treatment.

  • 448.
    Olsson, Karl Wilhelm
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Perinatal, neonatal och barnkardiologisk forskning.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Jonzon, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Perinatal, neonatal och barnkardiologisk forskning.
    Sindelar, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Perinatal, neonatal och barnkardiologisk forskning.
    Insights image for exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22-27 weeks' gestation: [published in Pediatric Research volume 86, page 413 (2019)]2019Annet (Fagfellevurdert)
  • 449.
    Opstad, Trine Baur
    et al.
    Centre for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, 0450 Oslo, Norway..
    Alexander, Jan
    Norwegian Institute of Public Health, 0213 Oslo, Norway..
    Aaseth, Jan O
    Department of Research, Innlandet Hospital Trust, 2381 Brumunddal, Norway..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Seljeflot, Ingebjørg
    Centre for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, 0450 Oslo, Norway..
    Alehagen, Urban
    Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 581 83 Linköping, Sweden..
    Selenium and Coenzyme Q10 Intervention Prevents Telomere Attrition, with Association to Reduced Cardiovascular Mortality-Sub-Study of a Randomized Clinical Trial2022Inngår i: Nutrients, E-ISSN 2072-6643, Vol. 14, nr 16, artikkel-id 3346Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Short telomeres have been associated with ageing and cardiovascular disease. The influence on leukocyte telomere length (LTL) of long-term intervention with combined selenium and coenzyme Q10 is unknown. Our aim was to determine whether 42 months of selenium and coenzyme Q10 supplementation prevented telomere attrition and further cardiovascular mortality. The investigation is an explorative sub-study of a double-blind, placebo-controlled, randomized trial. Swedish citizens low in selenium (n = 118), aged 70-80 years, were included. Intervention time was 4 years, with 10 years' follow-up time. LTL was relatively quantified with PCR at baseline and after 42 months. At baseline, LTL (SD) was 0.954 (0.260) in the active treatment group and 1.018 (0.317) in the placebo group (p = 0.23). At 42 months, less shortening of LTL was observed after active treatment compared with placebo (+0.019 vs. -0.129, respectively, p = 0.02), with a significant difference in change basing the analysis on individual changes in LTL (p &lt; 0.001). Subjects suffering future death presented with significantly shorter LTL at 42 months than survivors [0.791 (0.190) vs. 0.941 (0.279), p = 0.01], with a significant difference in change of LTL according to cardiovascular mortality and survival (p = 0.03). To conclude, preservation of LTL after selenium and coenzyme Q10 supplementation associated with reduced cardiovascular mortality.

    Fulltekst (pdf)
    fulltext
  • 450. Ostlund, Eva
    et al.
    Al-Nashi, Maha
    Hamad, Rangeen Rafik
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Maria
    Bremme, Katarina
    Kahan, Thomas
    Normalized endothelial function but sustained cardiovascular risk profile 11 years following a pregnancy complicated by preeclampsia2013Inngår i: Hypertension Research, ISSN 0916-9636, E-ISSN 1348-4214, Vol. 36, nr 12, s. 1081-1087Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Women with a history of preeclampsia are at increased risk of future cardiovascular disease. Preeclampsia is associated with elevated blood pressure, inflammation and endothelial dysfunction, and these findings remain 1 year after delivery. Whether these abnormalities persist long after delivery, and whether they may contribute to future cardiovascular disease, is not well studied. We studied 15 women with a history of preeclampsia and 16 matched controls with an uncomplicated pregnancy 11 years following the index pregnancy; all had also been previously examined at 1 year. We assessed arterial stiffness (pulse wave analysis), 24 h ambulatory blood pressure and endothelial function (forearm flow-mediated dilatation and pulse wave analysis following β receptor agonist provocation), and determined markers of glucose and lipid metabolism, inflammation and vascular function. The preeclampsia group had higher blood pressures and reduced night/day blood pressure ratios, increased body mass index and reduced glucose tolerance, and increased levels of tissue necrosis factor receptor 1 and intracellular adhesion molecule-1, suggesting inflammatory and vascular activation. However, the endothelial impairment observed in the preeclampsia group at 1 year was normalized at 11 years, whereas the control group remained unchanged during follow-up. Our findings of higher blood pressures, impaired glucose tolerance and normalization of endothelial function 11 years after preeclampsia suggest cardiovascular risk factors present already before pregnancy to be more important than permanent endothelial damage for the increased risk of future cardiovascular complications in women with a history of preeclampsia.

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