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  • 151.
    Ali, Zafar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, Faisalabad, Pakistan.
    Zulfiqar, Shumaila
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Klar, Joakim
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ullah, Farid
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, Faisalabad, Pakistan.
    Khan, Ayaz
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, Faisalabad, Pakistan.
    Abdullah, Uzma
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, Faisalabad, Pakistan.
    Baig, Shahid
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, Faisalabad, Pakistan.
    Dahl, Niklas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Homozygous GRID2 missense mutation predicts a shift in the D-serine binding domain of GluD2 in a case with generalized brain atrophy and unusual clinical features2017Inngår i: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 18, nr 1, artikkel-id 144Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Spinocerebellar ataxias comprise a large and heterogeneous group of disorders that may present with isolated ataxia, or ataxia in combination with other neurologic or non-neurologic symptoms. Monoallelic or biallelic GRID2 mutations were recently reported in rare cases with cerebellar syndrome and variable degree of ataxia, ocular symptoms, hypotonia and developmental delay.

    CASE PRESENTATION: We report on a consanguineous family with autosomal recessive childhood onset of slowly progressive cerebellar ataxia and delayed psychomotor development in three siblings. MRI of an adult and affected family member revealed slightly widened cerebral and cerebellar sulci, suggesting generalized brain atrophy, and mild cerebellar atrophy. Using whole exome sequencing we identified a novel homozygous missense variant [c.2128C > T, p.(Arg710Trp)] in GRID2 that segregates with the disease. The missense variant is located in a conserved region encoding the extracellular serine-binding domain of the GluD2 protein and predicts a change in conformation of the protein.

    CONCLUSION: The widespread supratentorial brain abnormalities, absence of oculomotor symptoms, increased peripheral muscle tone and the novel missense mutation add to the clinical and genetic variability in GRID2 associated cerebellar syndrome. The neuroradiological findings in our family indicate a generalized neurodegenerative process to be taken into account in other families segregating complex clinical features and GRID2 mutations.

  • 152.
    Alimohammadi, Mohammad
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Björklund, Peyman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Hallgren, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Pöntynen, Nora
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Szinnai, Gabor
    Shikama, Noriko
    Keller, Marcel P
    Ekwall, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kinkel, Sarah A
    Husebye, Eystein S
    Gustafsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Peltonen, Leena
    Betterle, Corrado
    Perheentupa, Jaakko
    Åkerström, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Westin, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Scott, Hamish S
    Holländer, Georg A
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen2008Inngår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 358, nr 10, s. 1018-1028Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate the molecular pathogenesis of organ-specific autoimmunity in patients with APS-1, the autoantigen responsible for hypoparathyroidism, a hallmark of APS-1 and its most common autoimmune endocrinopathy, has not yet been identified. METHODS: We performed immunoscreening of a human parathyroid complementary DNA library, using serum samples from patients with APS-1 and hypoparathyroidism, to identify patients with reactivity to the NACHT leucine-rich-repeat protein 5 (NALP5). Subsequently, serum samples from 87 patients with APS-1 and 293 controls, including patients with other autoimmune disorders, were used to determine the frequency and specificity of autoantibodies against NALP5. In addition, the expression of NALP5 was investigated in various tissues. RESULTS: NALP5-specific autoantibodies were detected in 49% of the patients with APS-1 and hypoparathyroidism but were absent in all patients with APS-1 but without hypoparathyroidism, in all patients with other autoimmune endocrine disorders, and in all healthy controls. NALP5 was predominantly expressed in the cytoplasm of parathyroid chief cells. CONCLUSIONS: NALP5 appears to be a tissue-specific autoantigen involved in hypoparathyroidism in patients with APS-1. Autoantibodies against NALP5 appear to be highly specific and may be diagnostic for this prominent component of APS-1.

  • 153.
    Alimohammadi, Mohammad
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Dubois, Noemie
    Sköldberg, Filip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Hallgren, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Tradivel, Isabelle
    Hedstrand, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Haavik, Jan
    Husebye, Eystein
    Gustafsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Meloni, Antonella
    Janson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Vilattes, Bernard
    Kajosaari, Merja
    Egner, William
    Sargur, Ravishankar
    Amoura, Zahir
    Grimfeld, Alain
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Molekylär och morfologisk patologi.
    De Luca, Filippo
    Betterle, Corrado
    Perheentupa, Jaakko
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Pulmonary Autoimmunity as a Feature of Autoimmune Polyendocrine Syndrome Type 1 and Identification of KCNRG as a Bronchial Autoantigen2009Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, nr 11, s. 4396-4401Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

  • 154. Aliverti, A.
    et al.
    Kostic, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lo Mauro, Antonella
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Andersson-Olerud, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Quaranta, M.
    Pedotti, A.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Frykholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Effects of propofol anaesthesia on thoraco-abdominal volume variations during spontaneous breathing and mechanical ventilation2011Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, nr 5, s. 588-596Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Anaesthesia based on inhalational agents has profound effects on chest wall configuration and breathing pattern. The effects of propofol are less well characterised. The aim of the current study was to evaluate the effects of propofol anaesthesia on chest wall motion during spontaneous breathing and positive pressure ventilation. Methods We studied 16 subjects undergoing elective surgery requiring general anaesthesia. Chest wall volumes were continuously monitored by opto-electronic plethysmography during quiet breathing (QB) in the conscious state, induction of anaesthesia, spontaneous breathing during anaesthesia (SB), pressure support ventilation (PSV) and pressure control ventilation (PCV) after muscle paralysis. Results The total chest wall volume decreased by 0.41 +/- 0.08 l immediately after induction by equal reductions in the rib cage and abdominal volumes. An increase in the rib cage volume was then seen, resulting in total chest wall volumes 0.26 +/- 0.09, 0.24 +/- 0.10, 0.22 +/- 0.10 l lower than baseline, during SB, PSV and PCV, respectively. During QB, rib cage volume displacement corresponded to 34.2 +/- 5.3% of the tidal volume. During SB, PSV and PCV, this increased to 42.2 +/- 4.9%, 48.2 +/- 3.6% and 46.3 +/- 3.2%, respectively, with a corresponding decrease in the abdominal contribution. Breathing was initiated by the rib cage muscles during SB. Conclusion Propofol anaesthesia decreases end-expiratory chest wall volume, with a more pronounced effect on the diaphragm than on the rib cage muscles, which initiate breathing after apnoea.

  • 155.
    Allen, Marie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Engström, A-S.
    Meyers, S.
    Handt, O.
    Saldeen, Tom
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Rättsmedicin.
    von Haeseler, A.
    Pääbo, S.
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Mitochondrial DNA sequencing of shed hairs and saliva on robbery caps: sensitivity and matching probabilities1998Inngår i: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 43, nr 3, s. 453-464Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sequencing of mitochondrial DNA (mtDNA) has been used for human identification based on teeth and skeletal remains. Here, we describe an amplification system for the mtDNA control region (D-loop) suited for the analysis of shed hair, which constitutes the most common biological evidence material in forensic investigations. The success rate was over 90% when applied to evidence materials such as shed hair, saliva stains and saliva on stamps. The analysis of evidence materials collected from three similar robberies revealed the presence of mtDNA sequences identical to those of the suspects in the three crimes. The use of mtDNA control region sequences for individual identification was evaluated. The probability of identity by chance for the mtDNA types of the suspects in the robberies was found to vary between Pr = 0.017 - < 0.0017, depending on the reference population used, emphasizing the need for large population databases to obtain the appropriate estimate.

  • 156.
    Allen, Marie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Saldeen, Tom
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Rättsmedicin.
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Allele-specific HLA-DRB1 amplification of forensic evidence samples with mixed genotypes1995Inngår i: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 19, nr 3, s. 454-463Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A major problem in analyzing forensic casework samples is the presence of genetic material from more than one individual in the material evidence. For instance, in sexual assault cases the evidence (vaginal swabs) usually contains a majority of vaginal epithelial cells and varying amounts of sperm cells from the perpetrator. Samples with mixed genotypes are also common among other biological evidence materials such as nail scrapes and mixed bloodstains. We have developed an allele-specific amplification system for the highly polymorphic HLA class II DRB1 locus that permits the detection of individual alleles in a sample with mixed genotypes, independent of the initial frequency of the alleles. Using a set of eight allele-specific amplification primers and typing the amplified fragments with sequence-specific probes, most of the 60 DRB1 alleles can be resolved. The method is highly specific and sensitive, with the potential for amplifying 15 copies of a particular allele in a background of 3 x 10(5) copies of other alleles. The method was successfully applied to three forensic cases, where the material evidence consisted of sperm stains on panties, nail scrapes and bloodstains on skin. Thus the DRB1 allele-specific amplification system can be employed for the unambiguous determination of the presence of individual alleles in materials suspected to contain mixed genotypes, even when the alleles of interest constitute only a small fraction of the total DNA

  • 157.
    Allen, Marie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Saldeen, Tom
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Rättsmedicin.
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    PCR-based DNA typing of saliva on stamps and envelopes1994Inngår i: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 17, nr 3, s. 546-552Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In forensic cases involving mail bombs, extortion, kidnapping or threatening letters, biological evidence such as the saliva used to attach the stamp and seal the envelope could be used for genetic analysis. We have developed a highly sensitive semi-nested PCR method for the HLA-DRB1 locus; suitable for the analyses of very limited amounts of DNA. When applied to a set of stamps and envelopes with saliva from control individuals, typing results were consistent with those obtained using hairs drawn from the same individuals. No interference was found due to DNA from the fingerprints of people handling the letters. The system was applied to three forensic cases with threatening letters. The first case resulted in an exclusion of the suspect. In the second case, the suspect could not be excluded (probability of identical genotype by chance > 0.01). These results demonstrate that biological evidence in cases with threatening letters is amenable to genetic typing.

  • 158. Allen, Naomi E
    et al.
    Travis, Ruth C
    Appleby, Paul N
    Albanes, Demetrius
    Barnett, Matt J
    Black, Amanda
    Bueno-de-Mesquita, H Bas
    Deschasaux, Mélanie
    Galan, Pilar
    Goodman, Gary E
    Goodman, Phyllis J
    Gunter, Marc J
    Heliövaara, Markku
    Helzlsouer, Kathy J
    Henderson, Brian E
    Hercberg, Serge
    Knekt, Paul
    Kolonel, Laurence N
    Lasheras, Christina
    Linseisen, Jakob
    Metter, E Jeffrey
    Neuhouser, Marian L
    Olsen, Anja
    Pala, Valeria
    Platz, Elizabeth A
    Rissanen, Harri
    Reid, Mary E
    Schenk, Jeannette M
    Stampfer, Meir J
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Tangen, Catherine M
    Touvier, Mathilde
    Trichopoulou, Antonia
    van den Brandt, Piet A
    Key, Timothy J
    Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies.2016Inngår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 108, nr 11Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade.

    METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided.

    RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08).

    CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

  • 159.
    Al-Mashhadi, Ammar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Läckgren, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Ladjevardi, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Nevéus, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Stenberg, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Persson, A. Erik G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlstrom, Mattias
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Changes of arterial pressure following relief of obstruction in adults with hydronephrosis2018Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, nr 4, s. 216-224Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: As much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery.

    Materials and methods: Medical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients (35 years old; 95% CI 29–39). Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney.

    Results: Systolic (−11 mmHg; 95% CI 6–15 mmHg), diastolic (−8 mmHg; 95% CI 4–11 mmHg), and mean arterial (-9 mmHg; 95% CI 6–12) pressures were significantly reduced after relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37–41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction.

    Conclusions: In adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis.

  • 160.
    Almby, Kristina E.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Abrahamsson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lundqvist, Martin H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Hammar, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Thombare, Ketan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Panagiotou, Amalia
    Uppsala Univ Hosp, Dept Internal Med, Uppsala, Sweden.
    Karlsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Wiklund, Urban
    Umea Univ, Dept Radiat Sci, Biomed Engn, Umea, Sweden.
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery2019Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 181, nr 2, s. 161-171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).

    Design: Experimental hyperinsulinemic-hypoglycemic clamp study.

    Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.

    Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.

    Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

  • 161. Almqvist, Catarina
    et al.
    Adami, Hans-Olov
    Franks, Paul W.
    Groop, Leif
    Ingelsson, Erik
    Kere, Juha
    Lissner, Lauren
    Litton, Jan-Eric
    Maeurer, Markus
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Palmgren, Juni
    Pershagen, Göran
    Ploner, Alexander
    Sullivan, Patrick F.
    Tybring, Gunnel
    Pedersen, Nancy L.
    LifeGene - A large prospective population-based study of global relevance2011Inngår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 26, nr 1, s. 67-77Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting. LifeGene is designed both as a prospective cohort study and an infrastructure with repeated contacts of study participants approximately every 5 years. Index persons aged 18-45 years old will be recruited and invited to include their household members (partner and any children). A comprehensive questionnaire addressing cutting-edge research questions will be administered through the web with short follow-ups annually. Biosamples and physical measurements will also be collected at baseline, and re-administered every 5 years thereafter. Event-based sampling will be a key feature of LifeGene. The household-based design will give the opportunity to involve young couples prior to and during pregnancy, allowing for the first study of children born into cohort with complete pre-and perinatal data from both the mother and father. Questions and sampling schemes will be tailored to the participants' age and life events. The target of LifeGene is to enrol 500,000 Swedes and follow them longitudinally for at least 20 years.

  • 162.
    Alström, Ulrica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Platelet Inhibition and Bleeding in Coronary Artery Bypass Surgery2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    A substantial number of patients undergoing cardiac surgery are on dual anti-platelet treatment with clopidogrel and aspirin. A disadvantage with this treatment is increased risk of bleeding. Bleeding is a complication of major concern associated with adverse outcome for the patient and increased hospital resource utilization. Great variability in individual response to clopidogrel has been reported. If in vitro measurements of platelet reactivity would correlate with clinical bleeding parameters, potential bleeders could be identified preoperatively.

    The aims of this thesis were: (1) to describe the degree of pre-operative platelet inhibition in patients scheduled for primary isolated coronary artery bypass graft surgery; (2) to prospectively investigate whether the pre-operative platelet inhibition correlated with intra- and postoperative bleeding and transfusion requirements; and (3) to test the ability of clinically relevant risk factors to predict re-exploration for bleeding. (4) In addition, a cost analysis was performed on patients re-explored for bleeding, to analyse the magnitude of added resource utilization and costs. Based on this, a cost model of prophylactic treatment with haemostatic drugs was calculated.

    Platelet function tests investigated were: (1) flow cytometry, (2) VASP, (3) VerifyNowSystem, (4) PlateletMapping (a modified TEG), and (5) PFA-100.

    Clinical risk factors for re-exploration and the influence of antiplatelet and antifibrinolytic therapy were evaluated in a retrospective analysis. Cost analysis at three cardiothoracic centres was performed in a case-control study.

    In conclusion, there was no clinically useful correlation between preoperative assessment of platelet inhibition and blood loss or transfusion requirements during coronary artery bypass surgery. Furthermore, there was only modest agreement between the methods evaluating ADP-receptor blockade.

    Pre-operative treatment with the P2Y12-receptor inhibitor clopidogrel was an essential risk factor for re-exploration due to bleeding. Except for clopidogrel, no strong clinical factor to predict the risk of re-exploration was identified.

    The resource utilisation costs were 47% higher in patients requiring re-exploration due to bleeding than in those not requiring re-exploration. Prolonged stay in the ICU and recovery ward accounted for half of the added cost, a third was due to the costs of surgery, one fifth due to increased cost of transfusions, and <2% was due to haemostatic drug treatment.

     

     

    Delarbeid
    1. The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment
    Åpne denne publikasjonen i ny fane eller vindu >>The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment
    Vise andre…
    2007 (engelsk)Inngår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 120, nr 3, s. 353-359Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    INTRODUCTION: Addition of clopidogrel to patients treated with ASA has been shown to decrease the incidence of in-stent thrombosis after percutaneous coronary interventions. However, it has also been reported that up to 30% of patients do not achieve adequate platelet inhibition from standard dosages of ASA and clopidogrel. There is a demand for reliable methods to measure the individual platelet inhibiting effect of this combination therapy. MATERIALS AND METHODS: The primary aim of the present investigation was to compare three methods for evaluation of the platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment. Thirty patients presenting for coronary angiography/PCI were included. Two patients were excluded due to technical problems. All patients were on 75-100 mg ASA/day for at least 8 days. Blood samples were analysed before and 16 h after a 300 mg clopidogrel bolus dose. The platelet inhibiting effect was measured with (1) Whole blood flow cytometry (17 patients); (2) a bed-side test, Platelet Mapping assay for the thrombelastograph (28 patients); and (3) PFA (Platelet function analyser) -100 (26 patients). RESULTS: With flow cytometry, the percentage of platelets expressing P-selectin (p=0.03) on their surface decreased significantly after the bolus dose of clopidogrel. There was also a reduction of platelets binding fibrinogen when stimulated with ADP. A significantly (p=0.002) increased platelet inhibition could also be demonstrated with Platelet Mapping. PFA-100 could not measure any significant platelet inhibiting effect of clopidogrel. CONCLUSION: A significant platelet inhibition could be demonstrated with flow cytometry and the Platelet Mapping assay, but not with PFA-100. However, levels of response for the individual patient with these three methods were inconsistent. Further studies are needed to evaluate how the results correlate to the clinical risk of thrombosis and bleeding.

    Emneord
    Clopidogrel, Flow cytometry, Thrombelastograph, Platelets, PFA-100
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-24441 (URN)10.1016/j.thromres.2006.10.009 (DOI)000247762600005 ()17137616 (PubMedID)
    Tilgjengelig fra: 2007-02-15 Laget: 2007-02-15 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    2. Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
    Åpne denne publikasjonen i ny fane eller vindu >>Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
    Vise andre…
    2009 (engelsk)Inngår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 124, nr 5, s. 572-577Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    INTRODUCTION: A substantial number of patients with coronary artery disease undergo cardiac surgery within five days of discontinuing anti-platelet treatment with aspirin and clopidogrel. The aims of this study were to describe the degree of platelet inhibition in patients with dual anti-platelet treatment scheduled for coronary artery bypass graft (CABG) surgery and to investigate whether the measured platelet inhibition correlated to intra- and postoperative risk for bleeding and transfusion requirements. MATERIAL AND METHODS: Sixty patients were included. Platelet inhibition was analysed with flow cytometry including phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP-assay) and two bed-side analyzers, VerifyNow-System and PlateletMapping, a modified thrombelastograph. All 60 patients were analysed with VerifyNow and PlateletMapping, and 48 were analysed with flow cytometry and VASP-assay. RESULTS: There was a correlation between the ADP-receptor inhibition as measured by VASP-assay and VerifyNowP2Y(12) (r = -0.29, p<0.05), and between VASP-assay and the expression of P-selectin (r = 0.29, p<0.05) as measured by flow cytometry when platelets were stimulated with 5 microM ADP. VerifyNowP2Y(12) was the only measurement of platelet inhibition correlated to total blood loss (Spearman r = 0.29, p=0.03) and red blood cell transfusion (Spearman r = 0.43, p<0.01) requirements, although this might be confounded by aprotinin treatment. CONCLUSION: We found a modest agreement between the methods for preoperative platelet inhibition, though not for PlateletMapping-MA(ADP). There was a correlation between preoperative platelet inhibition measured by VerifyNowP2Y(12) and surgical blood loss or transfusion requirements. However, for the individual patient, preoperative use of VerifyNowP2Y(12) as an instrument to decide bleeding and transfusion risk does not seem helpful.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-120242 (URN)10.1016/j.thromres.2009.06.024 (DOI)000271712800012 ()19631364 (PubMedID)
    Tilgjengelig fra: 2010-03-10 Laget: 2010-03-10 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    3.
    Posten ble ikke funnet. Det kan skyldes at posten ikke lenger er tilgjengelig eller det er feil id i adressefeltet.
    4.
    Posten ble ikke funnet. Det kan skyldes at posten ikke lenger er tilgjengelig eller det er feil id i adressefeltet.
  • 163.
    Alström, Ulrica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Granath, Fredrik
    Friberg, Orjan
    Ekbom, Anders
    Ståhle, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Risk factors for re-exploration due to bleeding after coronary artery bypass grafting2012Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 46, nr 1, s. 39-44Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. The study aimed to investigate relevant clinical risk factors for re-exploration due to bleeding after primary coronary artery bypass graft (CABG) surgery, and to evaluate the influence of antiplatelet and antifibrinolytic drugs. Design. Three retrospective analyses were performed on patients who underwent CABG: (1) Logistic regression was used to identify clinical risk factors for re-exploration (n = 3000). (2) A case-control study (n = 228) was used to obtain information on exposure of antithrombotic and hemostatic therapy. (3) Based on exposure to antiplatelet and antifibrinolytic therapy, and odds ratios (ORs) in multivariate logistic models, the proportion of re-explorations attributed to these drugs was calculated. Results. A receiver operating characteristic curve was created for clinical risk factors. The C-index was 0.64, indicating limited ability to predict re-exploration for bleeding. Clopidogrel was the only drug influencing the risk of re-exploration (OR 3.2, 95% CI 1.7-5.9). The harmful effect of clopidogrel was confirmed in multivariate model (OR 4.7, 95% CI 2.2-9.9), and aprotinin had a protective effect of the same magnitude (OR 0.2, 95% CI 0.1-0.6). Conclusions. Clopidogrel is an essential risk factor for re-exploration due to bleeding, and attributable to at least one-quarter of surveyed cases. Aside from pharmaceuticals, there are no strong clinical risk factors.

  • 164.
    Alström, Ulrica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Granath, Fredrik
    Oldgren, Jonas
    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).
    Ståhle, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Tydén, Hans
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery2009Inngår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 124, nr 5, s. 572-577Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: A substantial number of patients with coronary artery disease undergo cardiac surgery within five days of discontinuing anti-platelet treatment with aspirin and clopidogrel. The aims of this study were to describe the degree of platelet inhibition in patients with dual anti-platelet treatment scheduled for coronary artery bypass graft (CABG) surgery and to investigate whether the measured platelet inhibition correlated to intra- and postoperative risk for bleeding and transfusion requirements. MATERIAL AND METHODS: Sixty patients were included. Platelet inhibition was analysed with flow cytometry including phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP-assay) and two bed-side analyzers, VerifyNow-System and PlateletMapping, a modified thrombelastograph. All 60 patients were analysed with VerifyNow and PlateletMapping, and 48 were analysed with flow cytometry and VASP-assay. RESULTS: There was a correlation between the ADP-receptor inhibition as measured by VASP-assay and VerifyNowP2Y(12) (r = -0.29, p<0.05), and between VASP-assay and the expression of P-selectin (r = 0.29, p<0.05) as measured by flow cytometry when platelets were stimulated with 5 microM ADP. VerifyNowP2Y(12) was the only measurement of platelet inhibition correlated to total blood loss (Spearman r = 0.29, p=0.03) and red blood cell transfusion (Spearman r = 0.43, p<0.01) requirements, although this might be confounded by aprotinin treatment. CONCLUSION: We found a modest agreement between the methods for preoperative platelet inhibition, though not for PlateletMapping-MA(ADP). There was a correlation between preoperative platelet inhibition measured by VerifyNowP2Y(12) and surgical blood loss or transfusion requirements. However, for the individual patient, preoperative use of VerifyNowP2Y(12) as an instrument to decide bleeding and transfusion risk does not seem helpful.

  • 165.
    Alström, Ulrica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Levin, L-Å
    Ståhle, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Svedjeholm, R
    Friberg, Ö
    Cost analysis of re-exploration for bleeding after coronary artery bypass graft surgery2012Inngår i: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 108, nr 2, s. 216-222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Re-exploration for bleeding after cardiac surgery is an indicator of substantial haemorrhage and is associated with increased hospital resource utilization. This study aimed to analyse the costs of re-exploration and estimate the costs of haemostatic prophylaxis.

    METHODS:

    A total of 4232 patients underwent isolated, first-time, coronary artery bypass graft (CABG) surgery during 2005-8. Each patient re-explored for bleeding (n=127) was matched with two controls not requiring re-exploration (n=254). Cost analysis was based on resource utilization from completion of CABG until discharge. A mean cost per patient for re-exploration was calculated. Based on this, the net cost of prophylactic treatment with haemostatic drugs for preventing re-exploration was calculated.

    RESULTS:

    Patients undergoing re-exploration had higher exposure to clopidogrel before operation, prolonged stays in the intensive care unit, and more blood transfusions than controls. The mean incremental cost for re-exploration was (sic)6290 [95% confidence interval (CI) (sic)3408-(sic)9173] per patient, of which 48% [(sic)3001 (95% CI (sic)249-(sic)2147)] was due to prolonged stay, 31% [(sic)1928 (95% CI (sic)1710-(sic)2147)] to the cost of surgery/anaesthesia, 20% [(sic)1261 (95% CI (sic)1145-(sic)1378)] to the increased number of blood transfusions, and <2% [(sic)100 (95% CI (sic)39-(sic)161)] to the cost of haemostatic drugs. A cost model, at an estimated 50% efficacy for recombinant activated clotting factor VIIa and a 50% expected risk for re-exploration without prophylaxis, demonstrated that to be cost neutral, prophylaxis of four patients needed to result in one avoided re-exploration.

    CONCLUSIONS:

    The resource utilization costs were substantially higher in patients requiring re-exploration for bleeding. From a strict cost-effectiveness perspective, clinical interventions to prevent haemorrhage might be underutilized.

  • 166.
    Alström, Ulrica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Tydén, Hans
    Oldgren, Jonas
    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 kliniskt forskningscentrum (UCR).
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Ståhle, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment2007Inngår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 120, nr 3, s. 353-359Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: Addition of clopidogrel to patients treated with ASA has been shown to decrease the incidence of in-stent thrombosis after percutaneous coronary interventions. However, it has also been reported that up to 30% of patients do not achieve adequate platelet inhibition from standard dosages of ASA and clopidogrel. There is a demand for reliable methods to measure the individual platelet inhibiting effect of this combination therapy. MATERIALS AND METHODS: The primary aim of the present investigation was to compare three methods for evaluation of the platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment. Thirty patients presenting for coronary angiography/PCI were included. Two patients were excluded due to technical problems. All patients were on 75-100 mg ASA/day for at least 8 days. Blood samples were analysed before and 16 h after a 300 mg clopidogrel bolus dose. The platelet inhibiting effect was measured with (1) Whole blood flow cytometry (17 patients); (2) a bed-side test, Platelet Mapping assay for the thrombelastograph (28 patients); and (3) PFA (Platelet function analyser) -100 (26 patients). RESULTS: With flow cytometry, the percentage of platelets expressing P-selectin (p=0.03) on their surface decreased significantly after the bolus dose of clopidogrel. There was also a reduction of platelets binding fibrinogen when stimulated with ADP. A significantly (p=0.002) increased platelet inhibition could also be demonstrated with Platelet Mapping. PFA-100 could not measure any significant platelet inhibiting effect of clopidogrel. CONCLUSION: A significant platelet inhibition could be demonstrated with flow cytometry and the Platelet Mapping assay, but not with PFA-100. However, levels of response for the individual patient with these three methods were inconsistent. Further studies are needed to evaluate how the results correlate to the clinical risk of thrombosis and bleeding.

  • 167.
    Altai, Mohamed
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Perols, Anna
    Tsourma, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Mitran, Bogdan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Honarvar, Hadis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Robillard, Marc
    Rossin, Raffaella
    Ten Hoeve, Wolter
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Eriksson Karlström, Amelie
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Feasibility of affibody-based bioorthogonal chemistry-mediated radionuclide pretargeting2016Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, nr 3, s. 431-436Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Affibody molecules constitute a new class of probes for radionuclide tumor targeting. The small size of affibody molecules is favorable for rapid localization in tumors and clearance from circulation. However, high renal re-absorption of affibody molecules prevents the use of residualizing radiometals, including a number of promising low energy beta- and alpha-emitters, for radionuclide therapy. We tested a hypothesis that affibody-based pretargeting mediated by a bioorthogonal interaction between trans-cyclooctene (TCO) and tetrazine would provide higher accumulation of radiometals in tumor xenografts than in the kidneys.

    Methods:

    TCO was conjugated to the anti-HER2 affibody molecule Z2395. DOTA-tetrazine was labeled with indium-111 and lutetium-177. In vitro pretargeting was studied in HER2-expressing SKOV-3 and BT474 cell lines. In vivo studies were performed on BALB/C nu/nu mice bearing SKOV-3 xenografts.

    Results:

    125I-Z2395-TCO bound specifically to HER2-expressing cells in vitro with an affinity of 45±16 pM. 111In-tetrazine bound specifically and selectively to Z2395-TCO pre-treated cells. In vivo studies demonstrated HER2-specific 125I-Z2395-TCO accumulation in xenografts. TCO-mediated 111In-tetrazine localization was shown in tumors, when the radiolabeled tracer was injected 4 h after an injection of Z2395-TCO. At 1 h post injection, the tumor uptake of 111In-tetrazine and 177Lu-tetrazine was ca. 2-fold higher than the renal uptake. Pretargeting provided more than a 56-fold reduction of renal uptake of 111In in comparison with direct targeting.

    Conclusion:

    The feasibility of affibody-based bioorthogonal chemistry-mediated pretargeting was demonstrated. The use of pretargeting provides a substantial reduction of radiometal accumulation in kidneys, creating preconditions for palliative radionuclide therapy.

  • 168.
    Altai, Mohamed
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Tsourma, M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Mitran, Bogdan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Preclin PET Platform, Uppsala, Sweden..
    Honarvar, Hadis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap. Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Perols, A.
    KTH, Div Prot Technol, Stockholm, Sweden..
    Robillard, M.
    Tagworks Pharmaceut, Eindhoven, Netherlands..
    Rossin, R.
    Tagworks Pharmaceut, Eindhoven, Netherlands..
    ten Hoeve, W.
    Syncom BV, Groningen, Netherlands..
    Sandström, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Karlstrom, A. Eriksson
    KTH, Div Prot Technol, Stockholm, Sweden..
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Affibody-based bioorthogonal chemistry-mediated radionuclide pretargeting: proof-of-principle2015Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 42, nr S1, s. S246-S246Artikkel i tidsskrift (Annet vitenskapelig)
  • 169.
    Altomare, Daniele
    et al.
    Univ Geneva, Lab Neuroimaging Aging LANVIE, Geneva, Switzerland;Memory Clin, Univ Hosp Geneva, Geneva, Switzerland.
    Ferrari, Clarissa
    IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, Serv Stat, Via Pilastroni 4, I-25125 Brescia, Italy.
    Caroli, Anna
    Ist Ric Farmacol Mario Negri IRCCS, Med Imaging Unit, Bergamo, Italy.
    Galluzzi, Samantha
    IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, LANE, Brescia, Italy.
    Prestia, Annapaola
    IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, LANE, Brescia, Italy.
    van der Flier, Wiesje M.
    Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Alzheimer Ctr Amsterdam,Dept Neurol, Amsterdam, Netherlands;Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Epidemiol & Biostat, Amsterdam, Netherlands.
    Ossenkoppele, Rik
    Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Alzheimer Ctr Amsterdam,Dept Neurol, Amsterdam, Netherlands;Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Radiol & Nucl Med, Amsterdam, Netherlands;Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Malmo, Sweden.
    Van Berckel, Bart
    Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Alzheimer Ctr Amsterdam,Dept Neurol, Amsterdam, Netherlands;Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Radiol & Nucl Med, Amsterdam, Netherlands.
    Barkhof, Frederik
    Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Radiol & Nucl Med, Amsterdam, Netherlands;UCL, Inst Neurol, London, England;UCL, Inst Healthcare Engn, London, England.
    Teunissen, Charlotte E.
    Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Clin Chem,Neurochem Lab, Amsterdam, Netherlands.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Carter, Stephen F.
    Karolinska Inst, Alzheimer Neurobiol Ctr, Stockholm, Sweden;Univ Manchester, Wolfson Mol Imaging Ctr, Manchester, Lancs, England.
    Scholl, Michael
    Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Malmo, Sweden;Univ Gothenburg, Dept Psychiat & Neurochem, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden;UCL, Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, Queen Sq, London, England.
    Choo, Il Han
    Karolinska Inst, Alzheimer Neurobiol Ctr, Stockholm, Sweden;Chosun Univ, Sch Med, Dept Neuropsychiat, Gwangju, South Korea.
    Grimmer, Timo
    Tech Univ Munich, Dept Psychiat & Psychotherapy, Klinikum Rechts Isar, Munich, Germany.
    Redolfi, Alberto
    IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, LANE, Brescia, Italy.
    Nordberg, Agneta
    Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden;Karolinska Univ Hosp, Aging Theme, Stockholm, Sweden.
    Scheltens, Philip
    Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Alzheimer Ctr Amsterdam,Dept Neurol, Amsterdam, Netherlands.
    Drzezga, Alexander
    Univ Cologne, Dept Nucl Med, Cologne, Germany.
    Frisoni, Giovanni B.
    Univ Geneva, Lab Neuroimaging Aging LANVIE, Geneva, Switzerland;IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, LANE, Brescia, Italy;Memory Clin, Univ Hosp Geneva, Geneva, Switzerland.
    Prognostic value of Alzheimer's biomarkers in mild cognitive impairment: the effect of age at onset2019Inngår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 266, nr 10, s. 2535-2545Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer's biomarkers in a large sample of patients with mild cognitive impairment (MCI). Methods We measured A beta 42, t-tau, hippocampal volume on magnetic resonance imaging (MRI) and cortical metabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET) in 188 MCI patients followed for at least 1 year. We categorised patients into earlier and later onset (EO/LO). Receiver operating characteristic curves and corresponding areas under the curve (AUCs) were performed to assess and compar the biomarker prognostic performances in EO and LO groups. Linear Model was adopted for estimating the time-to-progression in relation with earlier/later onset MCI groups and biomarkers. Results In earlier onset patients, all the assessed biomarkers were able to predict cognitive decline (p < 0.05), with FDG-PET showing the best performance. In later onset patients, all biomarkers but t-tau predicted cognitive decline (p < 0.05). Moreover, FDG-PET alone in earlier onset patients showed a higher prognostic value than the one resulting from the combination of all the biomarkers in later onset patients (earlier onset AUC 0.935 vs later onset AUC 0.753, p < 0.001). Finally, FDG-PET showed a different prognostic value between earlier and later onset patients (p = 0.040) in time-to-progression allowing an estimate of the time free from disease. Discussion FDG-PET may represent the most universal tool for the establishment of a prognosis in MCI patients and may be used for obtaining an onset-related estimate of the time free from disease.

  • 170.
    Aludden, Hanna
    et al.
    Aalborg Univ Hosp, Dept Oral & Maxillofacial Surg, Aalborg, Denmark..
    Dahlin, Anna
    Univ Gothenburg, BIOMATCELL VINN Excellence Ctr, Inst Surg Sci, Dept Biomat,Sahlgrenska Acad, Gothenburg, Sweden..
    Starch-Jensen, Thomas
    Aalborg Univ Hosp, Dept Oral & Maxillofacial Surg, Aalborg, Denmark..
    Dahlin, Christer
    Univ Gothenburg, BIOMATCELL VINN Excellence Ctr, Inst Surg Sci, Dept Biomat,Sahlgrenska Acad, Gothenburg, Sweden.;NU Hosp Org, Dept Oral & Maxillofacial Surg, Trollhattan, Sweden..
    Mordenfeld, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Käkkirurgi. Publ Hlth Serv, Dept Oral & Maxillofacial Surg, Gavle, Sweden.
    Histomorphometric analyses of area fraction of different ratios of Bio-Oss((R)) and bone prior to grafting procedures - An in vitro study to demonstrate a baseline2018Inngår i: Clinical Oral Implants Research, ISSN 0905-7161, E-ISSN 1600-0501, Vol. 29, nr 2, s. 185-191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The objective of this study was to estimate the area fraction of different ratios of Bio-Oss((R)) and bone, prior to grafting in an in vitro model to demonstrate a histomorphometric baseline.

    Methods: Bio-Oss((R)) particles were mixed with autogenous bone from pig jaw in three different ratios (50:50, 80:20 and 100:0) and packed in rice paper in a standardized procedure. Histomorphometric analyses were performed in 25 specimens and 74 regions of interest. The area percentage of Bio-Oss((R)), bone, and non-mineralized tissue (NMT) were calculated. Results were reported as mean values and 95% confidence interval (CI).

    Results: The mean area fraction of Bio-Oss((R)) was 20.6% (CI: 18.2-23) in the 50:50 mixture, 33.6% (CI: 29.7-37.6) in the 80:20 mixture, and 43.4% (CI: 40.5-46.3) in the 100:0 mixture. The mean area fraction of NMT was 60.5% (CI: 57.9-63.1) in the 50:50 mixture, 59.6% (CI: 56.4-62.7) in the 80:20 mixture, and 56.6% (CI: 53.7-59.5) in the 100:0 mixture. The mean area fraction of bone was 18.9% (CI: 16.9-20.9) in the 50:50 mixture and 6.8% (CI: 5-8.6) in the 80:20 mixture.

    Conclusion: There is a great difference in the clinically estimated percentage and the histomorphometrically evaluated percentage of Bio-Oss((R)) at baseline, prior to grafting. The area fraction of different tissues presented in this study may be beneficial as guidance for histomorphometrical baseline calculations when different mixtures of Bio-Oss((R)) and autogenous bone are used as grafting materials.

  • 171.
    Aludden, Hanna
    et al.
    Aalborg Univ Hosp, Dept Oral & Maxillofacial Surg, 18-22 Hobrovej, DK-9000 Aalborg, Denmark.
    Mordenfeld, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Käkkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Publ Hlth Serv, Dept Oral & Maxillofacial Surg, Gavle, Sweden.
    Hallman, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Publ Hlth Serv, Dept Oral & Maxillofacial Surg, Gavle, Sweden.
    Christensen, Ann-Eva
    Aalborg Univ Hosp, Unit Epidemiol & Biostatist, Aalborg, Denmark.
    Starch-Jensen, Thomas
    Aalborg Univ Hosp, Dept Oral & Maxillofacial Surg, 18-22 Hobrovej, DK-9000 Aalborg, Denmark.
    Osteotome-Mediated Sinus Floor Elevation With or Without a Grafting Material: A Systematic Review and Meta-analysis of Long-term Studies (>= 5-Years)2018Inngår i: Implant Dentistry, ISSN 1056-6163, E-ISSN 1538-2982, Vol. 27, nr 4, s. 488-497Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Objective: To test the hypothesis of no difference in the long-term treatment outcome after osteotome-mediated sinus floor elevation with or without a grafting material. Materials and Methods: A MEDLINE/PubMed, Cochrane Library, and EMBASE search in combination with a hand-search of relevant journals was conducted, including human studies published in English from January 1, 1986 to December 1, 2017. Results: One comparative and 7 noncomparative studies fulfilled the inclusion criteria. Survival of suprastructures had never been compared within the same study. Meta-analysis demonstrated an overall estimated patient-based implant survival of 94%. Gain in vertical alveolar bone height was similar with the 2 treatment modalities. Noncomparative studies demonstrated high long-term survival rate of suprastructures and implants with the 2 treatment modalities, as well as limited periimplant marginal bone loss. Conclusion: High long-term implant survival was demonstrated after osteotome-mediated sinus floor elevation with or without a grafting material. However, long-term randomized controlled trials comparing the 2 treatment modalities are sparse. Hence, conclusions drawn from this systematic review should be interpreted with caution.

  • 172.
    Alving, B
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Engstrom, K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wallin, R
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Saldeen, Tom
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Rättsmedicin.
    Effekt av 8 års intag av stabil fiskolja1996Inngår i: Hygiea, Vol. 105, s. 373-Artikkel, omtale (Annet vitenskapelig)
  • 173.
    An, Feng-Wei
    et al.
    Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol & Head Neck Surg, Beijing, Peoples R China;Chinese PLA Med Sch, Key Lab Hearing Impairment Sci, Minist Educ, Key Lab Hearing Impairment Prevent & Treatment Be, Beijing, Peoples R China.
    Yuan, Hu
    Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol & Head Neck Surg, Beijing, Peoples R China;Chinese PLA Med Sch, Key Lab Hearing Impairment Sci, Minist Educ, Key Lab Hearing Impairment Prevent & Treatment Be, Beijing, Peoples R China.
    Guo, Weiwei
    Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol & Head Neck Surg, Beijing, Peoples R China;Chinese PLA Med Sch, Key Lab Hearing Impairment Sci, Minist Educ, Key Lab Hearing Impairment Prevent & Treatment Be, Beijing, Peoples R China.
    Hou, Zhao-Hui
    Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol & Head Neck Surg, Beijing, Peoples R China;Chinese PLA Med Sch, Key Lab Hearing Impairment Sci, Minist Educ, Key Lab Hearing Impairment Prevent & Treatment Be, Beijing, Peoples R China.
    Cai, Jian-Ming
    Chinese Peoples Liberat Army Gen Hosp, Dept Radiol, Beijing, Peoples R China.
    Luo, Chun-Cai
    Chinese Peoples Liberat Army Gen Hosp, Dept Radiol, Beijing, Peoples R China.
    Yu, Ning
    Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol & Head Neck Surg, Beijing, Peoples R China;Chinese PLA Med Sch, Key Lab Hearing Impairment Sci, Minist Educ, Key Lab Hearing Impairment Prevent & Treatment Be, Beijing, Peoples R China.
    Jiang, Qing-Qing
    Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol & Head Neck Surg, Beijing, Peoples R China;Chinese PLA Med Sch, Key Lab Hearing Impairment Sci, Minist Educ, Key Lab Hearing Impairment Prevent & Treatment Be, Beijing, Peoples R China.
    Cheng, Wei
    Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol & Head Neck Surg, Beijing, Peoples R China;Chinese PLA Med Sch, Key Lab Hearing Impairment Sci, Minist Educ, Key Lab Hearing Impairment Prevent & Treatment Be, Beijing, Peoples R China.
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Yang, Shi-Ming
    Chinese PLA Med Sch, Key Lab Hearing Impairment Sci, Minist Educ, Key Lab Hearing Impairment Prevent & Treatment Be, Beijing, Peoples R China.
    Establishment of a Large Animal Model for Eustachian Tube Functional Study in Miniature Pigs2019Inngår i: Anatomical Record Part A-discoveries in Molecular Cellular and Evolutionary Biology, ISSN 1552-4884, E-ISSN 1932-8494, Vol. 302, nr 6, s. 1024-1038Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study was performed to investigate whether miniature pigs are a suitable animal model for studies of the Eustachian tube (ET). Sixteen Chinese experimental miniature pigs were used in this investigation. Ten animals were used for anatomical and morphometric analyses to obtain qualitative and quantitative information regarding the ET. Three animals were used for histological analysis to determine the fine structure of ET cross-sections. Three animals were used to investigate the feasibility of balloon dilation of the Eustachian tube (BDET). The anatomical study indicated that the pharyngeal orifice and tympanic orifice of the miniature pig ET are located at the posterior end of the nasal lateral wall and anterior wall of the middle ear cavity, respectively. The cartilaginous tube was seen to pass through the whole length of the ET, the length of the cartilaginous part of the ET and the diameter of the isthmus were similar between humans and miniature pigs. The inclination of the ET in miniature pigs was larger than that in humans. The gross histology seemed to be slightly different between miniature pig and human, but the fine structures were essentially the same in both species. BDET experiments verified that the miniature pig model is suitable as a model for clinical operations. The miniature pig ET corresponds very well to that of humans. In addition, the miniature pig ET is suitable as a model for clinical operations. Therefore, the miniature pig is a valid animal model for ET study. 

  • 174.
    Anantharaman, Devasena
    et al.
    Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France..
    Muller, David C.
    Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France..
    Lagiou, Pagona
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, Athens, Greece..
    Ahrens, Wolfgang
    BIPS, Leibniz Inst Prevent Res & Epidemiol, Bremen, Germany.;Univ Bremen, Fac Math & Comp Sci, Bremen, Germany..
    Holcatova, Ivana
    Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic..
    Merletti, Franco
    Univ Turin, Dept Med Sci, Canc Epidemiol Unit, Turin, Italy..
    Kjaerheim, Kristina
    Canc Registry Norway, Oslo, Norway..
    Polesel, Jerry
    CRO Aviano Natl Canc Inst, Unit Epidemiol & Biostat, Aviano, Italy..
    Simonato, Lorenzo
    Univ Padua, Dept Mol Med, Lab Publ Hlth & Populat Studies, Padua, Italy..
    Canova, Cristina
    Univ Padua, Dept Mol Med, Lab Publ Hlth & Populat Studies, Padua, Italy..
    Castellsague, Xavier
    CIBERESP, IDIBELL, ICO, Unit Infect & Canc, Barcelona, Spain..
    Macfarlane, Tatiana V.
    Univ Aberdeen, Sch Med & Dent, Aberdeen, Scotland..
    Znaor, Ariana
    Croatian Natl Inst Publ Hlth, Croatian Natl Canc Registry, Zagreb, Croatia.;Int Agcy Res Canc, Sect Canc Surveillance, Lyon, France..
    Thomson, Peter
    Newcastle Univ, Ctr Oral Hlth Res, Newcastle Upon Tyne, Tyne & Wear, England..
    Robinson, Max
    Newcastle Univ, Ctr Oral Hlth Res, Newcastle Upon Tyne, Tyne & Wear, England..
    Conway, David I.
    Univ Glasgow, Sch Dent, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland..
    Healy, Claire M.
    Trinity Coll Dublin, Sch Dent Sci, Dublin, Ireland..
    Tjönneland, Anne
    Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark..
    Westin, Ulla
    Lund Univ, Dept Otorhinolaryngol Malmo & Lund, Lund, Sweden..
    Ekström, Johanna
    Lund Univ, Dept Clin Sci, Lund, Sweden..
    Chang-Claude, Jenny
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany..
    Kaaks, Rudolf
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany..
    Overvad, Kim
    Inst Publ Hlth, Aarhus, Denmark..
    Drogan, Dagmar
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Nuthetal, Germany..
    Hallmans, Göran
    Umea Univ, Dept Biobank Res, Umea, Sweden..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Bueno-de-Mesquita, H. B.
    Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands.;Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia..
    Peeters, Petra H.
    Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands.;Imperial Coll London, Sch Publ Hlth, MRC PHE, London, England..
    Agudo, Antonio
    ICO, Unit Nutr & Canc, Barcelona, Spain..
    Larranaga, Nerea
    BIODonostia Res Inst, Basque Hlth Dept, Publ Hlth Div Gipuzkoa, San Sebastian, Spain.;CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Travis, Ruth C.
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy..
    Barricarte, Aurelio
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;Navarre Publ Hlth Inst, Pamplona, Spain..
    Trichopoulou, Antonia
    Hellen Hlth Fdn, Athens, Greece.;Acad Athens, Bur Epidemiol Res, Athens, Greece..
    George, Saitakis
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, Athens, Greece.;Hellen Hlth Fdn, Athens, Greece..
    Trichopoulos, Dimitrios
    Hellen Hlth Fdn, Athens, Greece.;Acad Athens, Bur Epidemiol Res, Athens, Greece.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Ramon Quiros, J.
    Publ Hlth Directorate Asturias, Oviedo, Spain..
    Grioni, Sara
    Fdn IRCCS, Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy..
    Sacerdote, Carlotta
    Univ Turin, Citta Salute & Sci Hosp, Canc Epidemiol Unit, Turin, Italy.;Ctr Canc Prevent CPO, Turin, Italy..
    Navarro, Carmen
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.;Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain..
    Sanchez, Maria-Jose
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;Univ Granada, Inst Invest Biosanitaria, Granada, Spain..
    Tumino, Rosario
    Civ MP Arezzo Hosp, Canc Registry, Asp Ragusa, Ragusa, Italy.;Civ MP Arezzo Hosp, Histopathol Unit, Asp Ragusa, Ragusa, Italy..
    Severi, Gianluca
    Human Genet Fdn HuGeF, Turin, Italy.;Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia..
    Boutron-Ruault, Marie-Christine
    INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Villejuif, France.;Univ Paris 11, Villejuif, France.;Inst Gustave Roussy, Villejuif, France..
    Clavel-Chapelon, Francoise
    INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Villejuif, France.;Univ Paris 11, Villejuif, France.;Inst Gustave Roussy, Villejuif, France..
    Panico, Salvatore
    Univ Naples Federico II, Dipartimento Med Clin & Chirurgia, Naples, Italy..
    Weiderpass, Elisabete
    Arctic Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway.;Canc Registry Norway, Oslo, Norway.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Folkhalsan Res Ctr, Dept Genet Epidemiol, Helsinki, Finland..
    Lund, Eiliv
    Arctic Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway..
    Gram, Inger T.
    Arctic Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway..
    Riboli, Elio
    Imperial Coll London, Sch Publ Hlth, London, England..
    Pawlita, Michael
    German Canc Res Ctr, Heidelberg, Germany..
    Waterboer, Tim
    German Canc Res Ctr, Heidelberg, Germany..
    Kreimer, Aimee R.
    NCI, NIH, Bethesda, MD 20892 USA..
    Johansson, Mattias
    Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France..
    Brennan, Paul
    Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France..
    Combined effects of smoking and HPV16 in oropharyngeal cancer2016Inngår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 45, nr 3, s. 752-761Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.

    Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multicentre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.

    Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.

    Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.

  • 175. Anckarsäter, R.
    et al.
    Vasic, N.
    Jidéus, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Kristiansson, M.
    Zetterberg, H.
    Blennow, K.
    Anckarsäter, H.
    Cerebrospinal fluid protein reactions during non-neurological surgery2007Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 115, nr 4, s. 254-259Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective - To study changes in cerebrospinal fluid (CSF) protein markers of blood-CSF barrier integrity and immunological reactions during surgical stress. Subjects and methods - Thirty-five patients without neurological or psychiatric disorders undergoing knee replacements had CSF and serum samples drawn from spinal and arterial catheters before, 3 h after and the morning after surgery. Results - Serum albumin decreased during surgery and CSF albumin decreased during and after surgery, and, as a consequence, the CSF/serum albumin ratio decreased significantly during the study period, especially after the intervention. In contrast, CSF concentrations of beta-2-microglobuline (β2M) increased significantly during surgery and remained high. The CSF general marker beta-trace protein (βTP) remained unchanged. Conclusions - Central nervous system protein reactions to a non-neurological surgical intervention include sharply decreased permeability of albumin into the CSF and signs of intrathecal inflammatory activity.

  • 176. Anderberg, Leif
    et al.
    Annertz, MÃ¥rten
    Hedlund, Rune
    Hildingsson, Christer
    Karlberg, Mikael
    Lind, Bengt
    Ohlin, Acke
    Olerud, Claes
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    [Whiplash injury is not an indication for craniocervical fusion]2004Inngår i: Lakartidningen, ISSN 0023-7205, Vol. 101, nr 9, s. 806-7; discussion 807Artikkel i tidsskrift (Annet vitenskapelig)
  • 177.
    Anderberg, S. B.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Luther, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Physiological aspects of Toll-like receptor 4 activation in sepsis-induced acute kidney injury2017Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, nr 3, s. 575-590Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Sepsis-induced acute kidney injury (SI-AKI) is common and associated with high mortality. Survivors are at increased risk of chronic kidney disease. The precise mechanism underlying SI-AKI is unknown, and no curative treatment exists. Toll-like receptor 4 (TLR4) activates the innate immune system in response to exogenous microbial products. The result is an inflammatory reaction aimed at clearing a potential infection. However, the consequence may also be organ dysfunction as the immune response can cause collateral damage to host tissue. The purpose of this review is to describe the basis for how ligand binding to TLR4 has the potential to cause renal dysfunction and the mechanisms by which this may take place in gram-negative sepsis. In addition, we highlight areas for future research that can further our knowledge of the pathogenesis of SI-AKI in relation to TLR4 activation. TLR4 is expressed in the kidney. Activation of TLR4 causes cytokine and chemokine release as well as renal leucocyte infiltration. It also results in endothelial and tubular dysfunction in addition to altered renal metabolism and circulation. From a physiological standpoint, inhibiting TLR4 in large animal experimental SI-AKI significantly improves renal function. Thus, current evidence indicates that TLR4 has the ability to mediate SI-AKI by a number of mechanisms. The strong experimental evidence supporting a role of TLR4 in the pathogenesis of SI-AKI in combination with the availability of pharmacological tools to target TLR4 warrants future human studies.

  • 178. Andersen, B
    et al.
    Matzsch, T
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Bergqvist, David
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Eriksson, B
    Torholm, C
    Location of postoperative deep vein thrombosis in relation to age and survival.1997Inngår i: Intern J Risk & Safety Med, Vol. 10, s. 229-Artikkel i tidsskrift (Fagfellevurdert)
  • 179. Andersen, BS
    et al.
    Jensen, HP
    Borris, LC
    Lassen, MR
    Matzsch, T
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Bergqvist, David
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Eriksson, BI
    Torholm, C
    Survival in patients undergoing total hip arhtroplasty in relation to thromboprophylaxis with low molecular weight heparin: a long-term follow-up study.1996Inngår i: Int J Risk & Safety in Med, Vol. 8, s. 251-Artikkel i tidsskrift (Fagfellevurdert)
  • 180.
    Andersen, Kasper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Farahmand, Bahman
    Ahlbom, Anders
    Held, Claes
    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).
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study2013Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, nr 47, s. 3624-3631Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS:

    We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event.

    METHODS AND RESULTS:

    All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races.

    CONCLUSIONS:

    Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.

  • 181.
    Andersen, Kasper
    et al.
    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).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Muscle Morphology And Risk Of Cardiovascular Disease2010Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, s. E353-E353Artikkel i tidsskrift (Annet vitenskapelig)
  • 182.
    Andersen, Kasper
    et al.
    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.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Skeletal muscle morphology and risk of cardiovascular disease in elderly men2015Inngår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, nr 2, s. 231-239Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN:

    Population-based cohort study.

    METHODS:

    We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS:

    During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS:

    Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

  • 183. Andersen, Lise Geisler
    et al.
    Ängquist, Lars
    Gamborg, Michael
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bengtsson, Calle
    Canoy, Dexter
    Eriksson, Johan G.
    Eriksson, Marit
    Järvelin, Marjo-Riitta
    Lissner, Lauren
    Nilsen, Tom I.
    Osler, Merete
    Overvad, Kim
    Rasmussen, Finn
    Salonen, Minna K.
    Schack-Nielsen, Lene
    Tammelin, Tuija H.
    Tuomainen, Tomi-Pekka
    Sørensen, Thorkild I. A.
    Baker, Jennifer L.
    Birth weight in relation to leisure time physical activity in adolescence and adulthood: meta-analysis of results from 13 nordic cohorts2009Inngår i: PloS one, ISSN 1932-6203, Vol. 4, nr 12, s. e8192-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Prenatal life exposures, potentially manifested as altered birth size, may influence the later risk of major chronic diseases through direct biologic effects on disease processes, but also by modifying adult behaviors such as physical activity that may influence later disease risk. METHODS/PRINCIPAL FINDINGS: We investigated the association between birth weight and leisure time physical activity (LTPA) in 43,482 adolescents and adults from 13 Nordic cohorts. Random effects meta-analyses were performed on categorical estimates from cohort-, age-, sex- and birth weight specific analyses. Birth weight showed a reverse U-shaped association with later LTPA; within the range of normal weight the association was negligible but weights below and above this range were associated with a lower probability of undertaking LTPA. Compared with the reference category (3.26-3.75 kg), the birth weight categories of 1.26-1.75, 1.76-2.25, 2.26-2.75, and 4.76-5.25 kg, had odds ratios of 0.67 (95% confidence interval: 0.47, 0.94), 0.72 (0.59, 0.88), 0.89 (0.79, 0.99), and 0.65 (0.50, 0.86), respectively. The shape and strength of the birth weight-LTPA association was virtually independent of sex, age, gestational age, educational level, concurrent body mass index, and smoking. CONCLUSIONS/SIGNIFICANCE: The association between birth weight and undertaking LTPA is very weak within the normal birth weight range, but both low and high birth weights are associated with a lower probability of undertaking LTPA, which hence may be a mediator between prenatal influences and later disease risk.

  • 184.
    Andersen, Mikkel Österheden
    et al.
    Reg Southern Denmark, Ctr Spine Surg & Res, Middelfart, Denmark;Univ Southern Denmark, Odense, Denmark.
    Fritzell, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Capio St Goran Hosp, Stockholm, Sweden;Qulturum Ctr Learning & Innovat Healthcare, Jonkoping, Sweden.
    Eiskjaer, Sören Peter
    Aalborg Univ Hosp, Aalborg C, Denmark.
    Lagerbäck, Tobias
    Karolinska Univ Hosp, Huddinge, Sweden;Karolinska Inst, Huddinge, Sweden.
    Hägg, Olle
    Spine Ctr Goteborg, Gothenburg, Sweden.
    Nordvall, Dennis
    Qulturum Ctr Learning & Innovat Healthcare, Jonkoping, Sweden.
    Lönne, Greger
    Innlandet Hosp Trust, Lillehammer, Norway;Trondheim Reg & Univ Hosp, St Olavs Hosp, Trondheim, Norway.
    Solberg, Tore
    Univ Hosp Northern Norway, Tromso, Norway;Arctic Univ Norway, Tromso, Norway.
    Jacobs, Wilco
    van Hooff, Miranda
    Sint Maartenskliniek, Nijmegen, Netherlands;Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands.
    Gerdhem, Paul
    Karolinska Univ Hosp, Huddinge, Sweden;Karolinska Inst, Huddinge, Sweden.
    Gehrchen, Martin
    Univ Copenhagen, Rigshosp, Copenhagen, Denmark.
    Surgical Treatment of Degenerative Disk Disease in Three Scandinavian Countries: An International Register Study Based on Three Merged National Spine Registers2019Inngår i: Global Spine Journal, ISSN 2192-5682, E-ISSN 2192-5690, Vol. 9, nr 8, s. 850-858Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Study Design: Observational study of prospectively collected data.

    Objectives: Patients with chronic low back pain resistant to nonoperative treatment often face a poor prognosis for recovery. The aim of the current study was to compare the variation and outcome of surgical treatment of degenerative disc disease in the Scandinavian countries based on The International Consortium for Health Outcomes Measurement core spine data sets.

    Methods: Anonymized individual level data from 3 national registers were pooled into 1 database. At the time of surgery, the patient reports data on demographics, lifestyle topics, comorbidity, and data on health-related quality of life such as Oswestry Disability Index, Euro-Qol-5D, and back and leg pain scores. The surgeon records diagnosis, type of surgery performed, and complications. One-year follow-ups are obtained with questionnaires. Baseline and 1-year follow-up data were analyzed to expose any differences between the countries.

    Results: A total of 1893 patients were included. At 1-year follow-up, 1315 (72%) patients responded. There were statistically significant baseline differences in age, smoking, comorbidity, frequency of previous surgery and intensity of back and leg pain. Isolated fusion was the primary procedure in all the countries ranging from 84% in Denmark to 76% in Sweden. There was clinically relevant improvement in all outcome measures except leg pain.

    Conclusions: In homogenous populations with similar health care systems the treatment traditions can vary considerably. Despite variations in preoperative variables, patient reported outcomes improve significantly and clinically relevant with surgical treatment.

  • 185.
    Anderson, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Boström, Marja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Pfaller, Kristian
    Glueckert, Rudolf
    Schrott-Fischer, Annelies
    Gerdin, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Structure and locomotion of adult in vitro regenerated spiral ganglion growth cones: a study using video microscopy and SEM2006Inngår i: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 215, nr 1-2, s. 97-107Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuronal development and neurite regeneration depends on the locomotion and navigation of nerve growth cones (GCs). There are few detailed descriptions of the GC function and structure in the adult auditory system. In this study, GCs of adult dissociated and cultured spiral ganglion (SG) neurons were analyzed in vitro utilizing combined high resolution scanning electron microscopy (SEM) and time lapse video microscopy (TLVM). Axon kinesis was assessed on planar substratum with growth factors BDNF, NT-3 and GDNF. At the nano-scale level, lamellipodial abdomen of the expanding GC was found to be decorated with short surface specializations, which at TLVM were considered to be related to their crawling capacity. Filopodia were devoid of these surface structures, supporting its generally described sensory role. Microspikes appearing on lamellipodia and axons, showed circular adhesions, which at TLVM were found to provide anchorage of the navigating and turning axon. Neurons and GCs expressed the DCC-receptor for the guidance molecule netrin-1. Asymmetric ligand-based stimulation initiated turning responses suggest that this attractant cue influences steering of GC in adult regenerating auditory neurites. Hopefully, these findings may be used for ensuing tentative navigation of spiral ganglion neurons to induce regenerative processes in the human ear.

  • 186. Anderson, Malin
    et al.
    Johnston, T.A.
    Newman, P.D.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Internalization of nanoparticles into spiral ganglion cells2009Inngår i: Journal of nanoneuroscience, ISSN 1939-0637, Vol. 1, nr 1, s. 75-84Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The delivery of drugs or genes to the inner ear in a controlled and biocompatible manner could lead to new treatments for conditions such as Ménière's disease, tinnitus, schwannomas of the ear, and for improving hearing. The concept of multifunctional nanoparticles, which are targetable, biodegradable, and traceable, has led to new approaches to controlled drug release and localized delivery to specific cell populations. Tissue-specific delivery can be achieved by functionally "addressed" nanostructures loaded with a therapeutic molecule. In the present study, we investigated the incorporation, distribution, and toxicology of amphiphilic block copolymer nanoparticles (NPs) in spiral ganglion (SG) cell cultures. Adult human and guinea pig SG neurons and glia/Schwann dissociated cell cultures were expanded, grown for several weeks, and then studied live using time-lapse video microscopy and high-resolution light microscopy. The cells were further characterized using immunocytochemistry for the neural marker TuJ1 and the glia cell markers S-100 and GFAP, and their morphology was studied in more detail using scanning electron microscopy (SEM). These cell cultures were exposed to fluorescently (Dil)-loaded NPs for different time periods and at different concentrations, and the uptake was studied using fluorescence microscopy. The study demonstrates that Dil-loaded NPs can be internalized into guinea pig SG neurons as well as into human and guinea pig SG glia/Schwann cells without indication of toxicity or reduced viability. After 4 hours, almost 100% of both the neurons and the glia cells had incorporated the NPs into the cytoplasm. No uptake could be detected in the nucleus and no evidence of internalization could be seen in axons or in the growth cone area of the neuron. Especially in the glia cells, the NPs were detected in small vesicles surrounding the nucleus and occasionally in the periphery of the cytoplasm. This information could lead to the development of more specialized NPs, targeting only SG neurons or Schwann cells.

  • 187.
    Andersson, Camilla