uu.seUppsala University Publications
Change search
Refine search result
1234567 1 - 50 of 61425
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. A, Borgström
    et al.
    P, Nerfeldt
    Friberg, Danielle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Adenotonsillotomy Versus Adenotonsillectomy in Pediatric Obstructive Sleep Apnea: An RCT.2017In: PediatricsArticle in journal (Refereed)
  • 2. A, Borgström
    et al.
    P, Nerfeldt
    Friberg, Danielle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Questionnaire OSA-18 has poor validity compared to polysomnography in pediatric obstructive sleep apnea.2013In: International journal of pediatric otorhinolaryngologyArticle in journal (Refereed)
  • 3. A, Borgström
    et al.
    P, Nerfeldt
    Friberg, Danielle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    O, Sunnergren
    J, Stalfors
    Trends and changes in paediatric tonsil surgery in Sweden 1987-2013: a population-based cohort study.2017In: BMJ openArticle in journal (Refereed)
  • 4. A Molarius, A
    et al.
    Granström, F
    Feldman, Inna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kalander Blomqvist, M
    Pettersson, H
    Ello, S
    Can financial insecurity and condescending treatment explain the higher prevalence of poor self-rated health in women than in men? A population-based cross-sectional study in Sweden2012Conference paper (Other academic)
  • 5.
    Aabel, Peder
    et al.
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway;Akershus Univ Hosp, Ear Nose & Throat Dept, Div Surg, Lorenskog, Norway;Univ Oslo, Inst Clin Med, Div Surg, Oslo, Norway.
    Utheim, Tor Paaske
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway;Univ Oslo, Inst Oral Biol, Fac Dent, Oslo, Norway.
    Olstad, Ole Kristoffer
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Dilley, Rodney James
    Ear Sci Inst Australia, Perth, WA, Australia;Univ Western Australia, Ear Sci Ctr, Nedlands, WA, Australia;Univ Western Australia, Ctr Cell Therapy & Regenerat Med, Nedlands, WA, Australia.
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Akershus Univ Hosp, Ear Nose & Throat Dept, Div Surg, Lorenskog, Norway;Univ Oslo, Inst Clin Med, Div Surg, Oslo, Norway.
    Transcription and microRNA Profiling of Cultured Human Tympanic Membrane Epidermal Keratinocytes2018In: Journal of the Association for Research in Otolaryngology, ISSN 1525-3961, E-ISSN 1438-7573, Vol. 19, no 3, p. 243-260Article in journal (Refereed)
    Abstract [en]

    The human tympanic membrane (TM) has a thin outer epidermal layer which plays an important role in TM homeostasis and ear health. The specialised cells of the TM epidermis have a different physiology compared to normal skin epidermal keratinocytes, displaying a dynamic and constitutive migration that maintains a clear TM surface and assists in regeneration. Here, we characterise and compare molecular phenotypes in keratinocyte cultures from TM and normal skin. TM keratinocytes were isolated by enzymatic digestion and cultured in vitro. We compared global mRNA and microRNA expression of the cultured cells with that of human epidermal keratinocyte cultures. Genes with either relatively higher or lower expression were analysed further using the biostatistical tools g:Profiler and Ingenuity Pathway Analysis. Approximately 500 genes were found differentially expressed. Gene ontology enrichment and Ingenuity analyses identified cellular migration and closely related biological processes to be the most significant functions of the genes highly expressed in the TM keratinocytes. The genes of low expression showed a marked difference in homeobox (HOX) genes of clusters A and C, giving the TM keratinocytes a strikingly low HOX gene expression profile. An in vitro scratch wound assay showed a more individualised cell movement in cells from the tympanic membrane than normal epidermal keratinocytes. We identified 10 microRNAs with differential expression, several of which can also be linked to regulation of cell migration and expression of HOX genes. Our data provides clues to understanding the specific physiological properties of TM keratinocytes, including candidate genes for constitutive migration, and may thus help focus further research.

  • 6.
    Aalto, Heidi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Föräldrars upplevelser av omvårdnaden av sitt sent underburna barn på BB: En intervjustudie2014Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Sent underburna barn vårdas ofta på BB-avdelning för fullgångna barn. De har högre frekvens av återinläggningar på sjukhus än fullgångna barn. De flesta studier kring underburna barns vistelse på sjukhus är inte gjorda specifikt på sent underburna barn. Syfte: Syftet är att utforska föräldrars upplevelser av omvårdnaden av sent underburna barn på en BB-avdelning i Sverige. I analysen användes det teoretiska begreppet empowerment. Metod: Studien är deskriptiv med en kvalitativ ansats. Telefonintervjuer användes som datainsamlingsmetod. Fem mammor och två pappor deltog i studien. Intervjuerna analyserades med innehållsanalys. Resultat/Slutsats: Föräldrarna upplevde att personalen antingen förmedlade empowerment eller inte. Omvårdnadsåtgärder kring barnet som gjorde föräldrarna mer delaktiga upplevdes mer positivt och omvårdnadsåtgärder som orsakade en separation mellan föräldrar och barn upplevdes mer negativt. Föräldrarna hade svårt att ifrågasätta personal, även om de upplevde att något kring omvårdnadsåtgärden kändes fel. Omvårdnadsåtgärder, utfördes inte alltid i enlighet med vetenskap och beprövad erfarenhet. Personalen kan utbildas mer i att främja empowerment i föräldrarollen och därmed även öka föräldradelaktigheten i barnets omvårdnad och möjligheten att se varje familjs unika behov. Mer forskning behövs om hur detta ska ske.

  • 7. Aalto, J
    et al.
    Pelkonen, S
    Kalimo, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Finne, J
    Mutant bacteriophage with non-catalytic endosialidase binds to bothbacterial and eukaryotic polysialic acid and can be used as probe for itsdetection.2001In: Glycoconj J, Vol. 18, p. 751-Article in journal (Refereed)
  • 8. Aalto, Kristiina
    et al.
    Korhonen, Laura
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Lahdenne, Pekka
    Pelkonen, Pirkko
    Lindholm, Dan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Nerve growth factor in serum of children with systemic lupus erythematosus is correlated with disease activity2002In: Cytokine, Vol. 20, p. 136-Article in journal (Refereed)
  • 9.
    Aalto, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Cloning and characterization of genes encoding proteins involved in the terminal stage of vesicular traffic in the yeast Saccharomyces cerevisiae1995In: VTT publication 255, Technical research centre of Finland, Espoo, Vol. 255Other (Other scientific)
  • 10. Aalto, Y
    et al.
    Forsgren, S
    Kjorell, U
    Bergh, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Franzen, L
    Henriksson, R
    Enhanced expression of neuropeptides in human breast cancer cell lines following irradiation1998In: Peptides, Vol. 19, p. 231-Article in journal (Refereed)
  • 11. Aaltonen, Kirsimari
    et al.
    Ahlin, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Salonen, Laura
    Fjällskog, Marie Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Heikkilä, Pävi
    Nevanlinna, Heli
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides2006In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 94, no 11, p. 1697-1702Article in journal (Refereed)
    Abstract [en]

    Cyclin A has in some studies been associated with poor breast cancer survival, although all studies have not confirmed this. Its prognostic significance in breast cancer needs evaluation in larger studies. Tissue microarray (TMA) technique allows a simultaneous analysis of large amount of tumours on a single microscopic slide. This makes a rapid screening of molecular markers in large amount of tumours possible. Because only a small tissue sample of each tumour is punched on an array, the question has arisen about the representativeness of TMA when studying markers that are expressed in only a small proportion of cells. For this reason, we wanted to compare cyclin A expression on TMA and on traditional large sections. Two breast cancer TMAs were constructed of 200 breast tumours diagnosed between 1997-1998. TMA slides and traditional large section slides of these 200 tumours were stained with cyclin A antibody and analysed by two independent readers. The reproducibility of the two readers' results was good or even very good, with kappa values 0.71-0.87. The agreement of TMA and large section results was good with kappa value 0.62-0.75. Cyclin A overexpression was significantly (P<0.001) associated with oestrogen receptor and progesterone receptor negativity and high grade both on TMA and large sections. Cyclin A overexpression was significantly associated with poor metastasis-free survival both on TMA and large sections. The relative risks for metastasis were similar on TMA and large sections. This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale.

  • 12. Aaltonen, Kirsimari
    et al.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Heikkilä, Päivi
    Aittomäki, Kristiina
    Tamminen, A.
    Nevanlinna, Heli
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    High cyclin B1 expression is associated with poor survival in breast cancer2009In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 100, no 7, p. 1055-60Article in journal (Refereed)
    Abstract [en]

    Cyclin B1 regulates the G(2)-M transition of the cell cycle. Cyclin B1 expression is higher in premalignant and malignant than normal breast lesions. Correlation of cyclin B1 expression with other histopathological variables and prognostic role in breast cancer are not fully understood. Traditionally used prognostic criteria identify large subset of patients to receive adjuvant chemotherapy and to be exposed to adverse effects. A reliable and simple method helping prognostic evaluation in breast cancer is needed. We analysed cyclin B1 expression on 1348 invasive breast cancers and studied correlations with other histopathological variables and survival. High cyclin B1 correlated with high tumour grade, large tumour size and positive nodal status, oestrogen and progesterone receptor negativity, positive HER2 and p53 status, young age at diagnosis, and high cyclin E, cyclin A and Ki67 expression. Among patients not given adjuvant chemotherapy high cyclin B1 was a strong predictor of shorter overall and metastasis-free survival (RR 3.74, P<0.0005 and RR 3.51, P<0.0005, respectively), and remained as an independent prognostic factor also in multivariate analysis (RR 1.80, P=0.04 and RR 2.31, P=0.02, respectively). This study suggests high cyclin B1 associates with aggressive phenotype and is an independent prognostic factor in breast cancer.

  • 13. Aaltonen, Kirsimari
    et al.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Landberg, Göran
    Eerola, Hannaleena
    Aittomäki, Kristiina
    Heikkilä, Päivi
    Nevanlinna, Heli
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer2009In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 113, no 1, p. 75-82Article in journal (Refereed)
    Abstract [en]

    Cyclins D1 and E play an important role in breast carcinogenesis. High cyclin E expression is common in hormone receptor negative and high grade aggressive breast cancer, whereas cyclin D1 in hormone receptor positive and low grade breast cancer. Experimental data has suggested that cyclin D1 and E mediate cell proliferation by different mechanisms in estrogen receptor (ER) positive and negative breast cancer. To test this hypotheses in large breast cancer material and to clarify the histopathological correlations of cyclin E and D1, especially the association with proliferation, we analyzed cyclin E and D1 immunohistochemical expression on breast tumour microarrays consisting of 1348 invasive breast cancers. High cyclin D1 expression was associated with high grade (P<0.0005), high cyclin A (P<0.0005) and Ki67 (P<0.0005) expression among ER positive but with low grade (P=0.05) and low Ki67 (P=0.01) expression among ER negative breast cancers. Cyclin E and D1 expression correlated positively in ER positive (P<0.0005) but had a negative correlation in ER negative tumours (P=0.004). Cyclin E associated with high grade among all tumours (P<0.0005). In conclusion, the findings of this study show that cyclin D1 has separate roles, and proliferation is driven by different mechanisms in ER positive and negative breast cancers.

  • 14. Aaltonen, Kirsimari
    et al.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Eerola, Hannaleena
    Aittomäki, Kristiina
    Heikkilä, Päivi
    Nevanlinna, Heli
    Familial breast cancers without mutations in BRCA1 or BRCA2 have low cyclin E and high cyclin D1 in contrast to cancers in BRCA mutation carriers2008In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 14, no 7, p. 1976-83Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We analyzed the expression of critical cell cycle regulators cyclin E and cyclin D1 in familial breast cancer, focusing on BRCA mutation-negative tumors. Cyclin E expression in tumors of BRCA1 or BRCA2 carriers is higher, and cyclin D1 expression lower, than in sporadic tumors. In familial non-BRCA1/2 tumors, cyclin E and cyclin D1 expression has not been studied. EXPERIMENTAL DESIGN: Cyclin E and cyclin D1 immunohistochemical expression was studied in tissue microarrays consisting of 53 BRCA1, 58 BRCA2, 798 familial non-BRCA1/2, and 439 sporadic breast tumors. RESULTS: In univariate analysis, BRCA1 tumors had significantly more frequently high cyclin E (88%) and low cyclin D1 (84%) expression than sporadic (54% and 49%, respectively) or familial non-BRCA1/2 (38% and 45%, respectively) tumors. BRCA2 tumors had significantly more frequently low cyclin D1 expression (68%) than sporadic or familial non-BRCA1/2 tumors and significantly more frequently high cyclin E expression than familial non-BRCA1/2 tumors. In a logistic regression model, cyclin expression, early age of onset, and estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) status were the independent factors most clearly distinguishing tumors of BRCA1 mutation carriers from other familial breast cancers. High cyclin E and low cyclin D1 expression were also independent predictors of BRCA2 mutation when compared with familial non-BRCA1/2 tumors. Most interestingly, lower frequency of high cyclin E expression independently distinguished familial non-BRCA1/2 tumors also from sporadic ones. CONCLUSIONS: Cyclin E and cyclin D1 expression distinguishes non-BRCA1/2 tumors from both sporadic and BRCA1- and BRCA2-associated tumors and may reflect different predisposition and pathogenesis in these groups.

  • 15. Aaltonen, Minna
    et al.
    Soukka, Hanna
    Halkola, Lauri
    Jalonen, Jarmo
    Kalimo, Hannu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Holopainen, Irma E
    Kääpä, Pekka O
    Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets2007In: Early Human Development, ISSN 0378-3782, E-ISSN 1872-6232, Vol. 83, no 2, p. 77-85Article in journal (Refereed)
    Abstract [en]

    Background: Meconium aspiration-induced hypertensive lung injury is frequently associated with neuronal damage. Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension, but its effects on the brain are poorly known. Aims: The aim of this study was to determine the effects of iNO treatment on the neuronal tissue after meconium aspiration. Study design: 71 anesthetized, catheterized and ventilated newborn piglets were studied for 6 h. Thirty-five piglets were instilled with a bolus of human meconium intratracheally and 36 piglets with saline instillation served as controls. Nineteen meconium piglets and 17 control piglets were continuously treated with 20 ppm of iNO, started at 30 min after the insult. The extent of neuronal injury was analysed histologically, and the levels of brain tissue lipid peroxidation products, reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were analysed as indicators of oxidative stress. Results: iNO treatment diminished the pulmonary hypertensive response caused by meconium aspiration, but did not change systemic or carotid hemodynamics. NO administration was associated with reduced neuronal injury and diminished amount of oxidized DNA in the hippocampus of the meconium piglets. Further, iNO treatment was associated with decreased level of GSH in the cortex, but no change in lipid peroxidation production or myeloperoxidase activity was detected in any of the studied brain areas. Conclusions: Our results suggest that iNO treatment may inhibit DNA oxidation and neuronal injury in the hippocampus, associated with newborn meconium aspiration.

  • 16. Aaltonen, Minna
    et al.
    Soukka, Hanna
    Halkola, Lauri
    Kalimo, Hannu
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology. Pathology.
    Holopainen, Irma E
    Kääpä, Pekka O
    Meconium aspiration induces neuronal injury in piglets.2005In: Acta Paediatr, ISSN 0803-5253, Vol. 94, no 10, p. 1468-75Article in journal (Refereed)
  • 17. Aaltonen, P
    et al.
    Brahme, A
    Lax, I
    Levernes, S
    Naslund, I
    Reitan, JB
    Turesson, I
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Specification of dose delivery in radiation therapy. Recommendation by the Nordic Association of Clinical Physics (NACP).1998In: Acta Oncol., Vol. 36 Suppl 10, p. 1-Article in journal (Refereed)
  • 18. Aaltonen, Pertti
    et al.
    Amory, John K
    Anderson, Richard A
    Behre, Hermann M
    Bialy, Gabriel
    Blithe, Diana
    Bone, Wilhelm
    Bremner, William J
    Colvard, Doug
    Cooper, Trevor G
    Elliesen, Jörg
    Gabelnick, Henry L
    Gu, Yi-Qun
    Handelsman, David J
    Johansson, Elof A B
    Kersemaekers, Wendy
    Liu, Peter
    MacKay, Trent
    Matlin, Stephen
    Mbizvo, Michael
    McLachlan, Robert I
    Meriggiola, Maria Cristina
    Mletzko, Stephan
    Mommers, Ellen
    Muermans, Hilde
    Nieschlag, Eberhard
    Odlind, Viveca
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Page, Stephanie T
    Radlmaier, Albert
    Sitruk-Ware, Regine
    Swerdloff, Ronald
    Wang, Christina
    Wu, Frederick
    Zitzmann, Michael
    10th Summit Meeting consensus: recommendations for regulatory approval for hormonal male contraception.2007In: J of Andrology, vol. 28, No 3 May/June, 2007, p. 362-363Conference paper (Other scientific)
  • 19. Aalto-Setälä, Katriina
    et al.
    Palomäki, Heikki
    Miettinen, Helena
    Vuorio, Alpo
    Kuusi, Timo
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Salonen, Oili
    Kaste, Markku
    Kontula, Kimmo
    Genetic risk factors and ischemic cerebrovascular disease: role of common variation of the genes encoding apolipoproteins and angiotensin-converting enzyme1998In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 30, no 2, p. 224-33Article in journal (Refereed)
    Abstract [en]

    DNA polymorphisms in genes encoding apolipoproteins (apo) A-I, C-III, B and E and angiotensin-converting enzyme (ACE) have been proposed to be associated with the risk of coronary artery disease (CAD). We studied whether the same genetic markers would also be associated with the occurrence and extent of atherosclerosis in cervical arteries. DNA samples from 234 survivors of stroke or a transient ischaemic attack aged 60 years or less were examined. The presence of atherosclerosis was assessed using aortic arch angiograms. The SstI polymorphism of apoA-I/C-III gene locus, the XbaI polymorphism of apoB gene, common apoE phenotypes and the insertion/deletion polymorphism of the ACE gene were analysed. The allele frequencies of the apoA-I/C-III, apoB, apoE or ACE gene did not differ between the groups with (n = 148) or without (n = 85) cervical atherosclerosis. However, when patients with at least one apoE4 allele and one X2 allele of apoB were combined and compared with those without either of them (E2E3 or E3E3 and X1X1), a significant association with the presence of cervical atherosclerosis was found (P = 0.03). The patients having the E2E3 phenotype had a significantly elevated serum triglyceride level compared with those with the E3E3 phenotype (P = 0.03). Serum high-density lipoprotein (HDL) cholesterol was lower in the patients with the E2E3 phenotype than in those with the E3E3 and E3E4 (P = 0.01 and P = 0.06, respectively). The apoB or ACE genotypes were not significantly associated with serum lipid or lipoprotein levels. There was no association between the ACE gene polymorphism and the occurrence of hypertension. In conclusion, the interaction of common apoB and apoE alleles may increase the risk of atherosclerosis in cervical arteries.

  • 20.
    Aanestad, O
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Flink, R
    Department of Neuroscience.
    Urinary stress incontinence. A urodynamic and quantitative electromyographic study of the perineal muscles.1999In: Acta Obstet. Gynecol. Scand., Vol. 78, p. 245-Article in journal (Refereed)
  • 21.
    Aanestad, Ö
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Flink, R
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Urinary stress incontinence: a urodynamic and quantitative electromyogrpahic study of the perineal muscles.1998In: Acta Obstet. Gynecol. Scand., Vol. 77, p. 1-Article in journal (Refereed)
  • 22. Aanestad, Ö
    et al.
    Flink, R
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Haggman, M
    Department of Surgical Sciences.
    Norlen, BJ
    Department of Surgical Sciences.
    Interference pattern in the urethral sphincter: a quantitative study in patients before and after radical retropubic prostatectomy.1998In: Scand J Urol and Nephrology, Vol. 32, p. 1-Article in journal (Refereed)
  • 23.
    Aanestad, Öystein
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Flink, Roland
    Norlen, Bo Johan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Interference pattern in perineal muscles: A quantitative electromyographic study in patients before and after transurethral surgery of the prostate.1997In: Neurourol Urodyn, Vol. 16, p. 101-Article in journal (Refereed)
  • 24.
    Aanestad, Øystein
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Quantitative electromyographic studies of the perineal muscles in normal subjects and patients suffering from anal or urinary incontinence1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of the study were to characterize the interference pattern in perineal muscles in healthy subjects with the use of quantitative EMG techniques, to evaluate if prostatic surgery had any effect on the interference pattern and furthermore to examine the interference pattern in the perineal muscles in patients suffering from urinary or anal incontinence.

    The interference pattern in the perineal muscles was examined with a computerized analysis, the Turns and Amplitude (T/A) analysis, and the innervation pattern of the muscles was examined with single fiber electromyography measuring the fiber density. Reference values were collected from 30 normal subjects. The patient material consisted of 20 males subjected to transurethral prostatectomy (TUR-P), 10 males who underwent radical retropubic prostatectomy (RRP), 20 patients suffering from anal incontinence and 24 women withurinary incontinence.

    T/A analysis of the interference pattern in the perineal muscles in normal subjects showed a significant increase in number of turns/sec and mean amplitude correlating to increasing force but no age-related changes.

    TUR-P and RRP did effect the innervation of the distal urethral sphincter muscle as shown by increased fiber density indicating a peripheral nerve lesion. T/A analysis did not shown any increased activation of the distal urethral sphincter as a compensation for the loss in bladder neck sphincter function but rather signs of decreasedcentral activation.

    Patients with idiopathic faecal incontinence showed signs of impaired innervation of the external anal sphincter muscle. A decreased interference pattern at maximal contraction indicated a reduced central activation of perineal muscles, in particular for patients with partial rupture of the external anal sphincter muscle. The reduced central activation could play a role for the aetiology of faecal incontinence.

    Patients with urinary stress incontinence also showed signs of impaired innervation of the external anal sphincter muscle as well as reduced interference pattern at maximal contraction and during continuous recording of the EMG activity during cystometry. A reduced central activation of the motor units was predicted as one factor involved in the aetiology.

  • 25. Aapro, Matti
    et al.
    Beguin, Yves
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gascon, Pere
    Hedenus, Michael
    Österborg, Anders
    Too-Low Iron Doses and Too Many Dropouts in Negative Iron Trial?2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 17, p. E525-E526Article in journal (Refereed)
  • 26. Aapro, Matti S.
    et al.
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bokemeyer, Carsten
    Cornes, Paul
    Foubert, Jan
    Gascon, Pere
    Glaspy, John
    Hellström-Lindberg, Eva
    Link, Hartmut
    Ludwig, Heinz
    Österborg, Anders
    Repetto, Lazzaro
    Soubeyran, Pierre
    Erythropoietins should be used according to guidelines2008In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 9, no 5, p. 412-3Article in journal (Refereed)
  • 27. Aardal, S
    et al.
    Aardal, NP
    Larsen, TH
    Angeletti, RH
    Stridsberg, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Taupenot, L
    Aunis, D
    Helle, KB
    Human pheochromocytoma: different patterns of catecholamine and chromogranins in the intact tumour, urine and serum in clinically unsuspected cases1996In: Scand J clin Lab Invest, Vol. 56, p. 511-Article in journal (Refereed)
  • 28. Aardal-Eriksson, E
    et al.
    Eriksson, T.E
    Holm, A-C
    Lundin, T
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Salivary cortisol and serum prolactin in relation to stress rating scales in a group of rescue workers1999In: Biol. Psychiatry, Vol. 46, p. 850-Article in journal (Refereed)
  • 29.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Ochala, Julien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Norman, Holly S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Eriksson, Lars I
    Göransson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Chen, Yi-Wen
    Hoffman, Eric P
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model2011In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, no 24, p. 1334-1350Article in journal (Refereed)
    Abstract [en]

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.

  • 30.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Department of anesthesiology, Karolinska Inistitute.
    Eriksson, Lars
    Department of anesthesiology, Karolinska Inistitute.
    Akkad, Hazem
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Chen, Yi-Wen
    Research center for genetic medicine.
    Hoffman, Eric
    Research center for genetic medicine.
    Lars, Larsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model2013In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 45, no 8, p. 312-320Article in journal (Refereed)
    Abstract [en]

    Severe muscle wasting is a debilitating condition in critically ill intensive care unit (ICU) patients, characterized by general muscle weakness and dysfunction, resulting in a prolonged mobilization, delayed weaning from the ventilator and a decreased quality of life post-ICU. The mechanisms underlying limbmuscle weakness in ICU patients are complex and involve the impact of primary disease, but also factors common to critically ill ICU patients such as sepsis, mechanical ventilation (MV), immobilization and systemic administration of corticosteroids (CS).  These factors may have additive negative effects on skeletal muscle structure and function, but their respective role alone remain unknown. The primary aim of this study was to examine how CS administration potentiates ventilator and immobilization-related limb muscle dysfunction at the gene level. Comparing biceps femoris gene expression in pigs exposed to MV and CS for five days with only MV pigs for the same duration of time showed a distinct deregulation of 186 genes using microarray. Surprisingly, the decreased force-generation capacity at the single muscle fiber reported in response to the addition of CS administration in mechanically ventilated and immobilized pigs was not associated with an additional up-regulation of proteolytic pathways. On the other hand, an altered expression of genes regulating kinase activity, cell cycle, transcription, channel regulation, oxidative stress response , cytoskeletal, sarcomeric and heat shock protein as well as protein synthesis at the translational level appear to play an additive deleterious role for the  limb muscle weakness in immobilized ICU patients.

     

  • 31.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Department of anesthesiology, Karolinska Inistitute.
    Eriksson, Lars
    Department of anesthesiology, Karolinska Inistitute.
    Chen, Yi-Wen
    Research center for genetic medicine.
    Hoffman, Eric P
    Research center for genetic medicine.
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model2012In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 44, no 18, p. 865-877Article in journal (Refereed)
    Abstract [en]

    Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis for five days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of more than 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity and transcriptional regulation. Genes involved in the regulation of the oxidative stress response, cytoskeletal/sarcomeric and heat shock proteins were on the other hand down-regulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.

  • 32.
    Aare, Sudhakar Reddy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Intensive Care Unit Muscle Wasting: Skeletal Muscle Phenotype and Underlying Molecular Mechanisms2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Acute quadriplegic myopathy (AQM), or critical illness myopathy, is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients characterized by generalized muscle wasting and weakness of limb and trunk muscles. A preferential loss of the thick filament protein myosin is considered pathognomonic of this disorder, but the myosin loss is observed relatively late during the disease progression. In attempt to explore the potential role of factors considered triggering AQM in sedated mechanically ventilated (MV) ICU patients, we have studied the early effects, prior to the myosin loss, of neuromuscular blockade (NMB), corticosteroids (CS) and sepsis separate or in combination in a porcine experimental ICU model. Specific interest has been focused on skeletal muscle gene/protein expression and regulation of muscle contraction at the muscle fiber level. This project aims at improving our understanding of the molecular mechanisms underlying muscle specific differences in response to the ICU intervention and the role played by the different triggering factors.

    The sparing of masticatory muscle fiber function was coupled to an up-regulation of heat shock protein genes and down-regulation of myostatin are suggested to be key factors in the relative sparing of masticatory muscles. Up-regulation of chemokine activity genes and down-regulation of heat shock protein genes play a significant role in the limb muscle dysfunction associated with sepsis. The effects of corticosteroids in the development of limb muscle weakness reveals up-regulation of kinase activity and transcriptional regulation genes and the down-regulation of heat shock protein, sarcomeric, cytoskeletal and oxidative stress responsive genes. In contrast to limb and craniofacial muscles, the respiratory diaphragm muscle responded differently to the different triggering factors. MV itself appears to play a major role for the diaphragm muscle dysfunction. By targeting these genes, future experiments can give an insight into the development of innovative treatments expected at protecting muscle mass and function in critically ill ICU patients.

    List of papers
    1. Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model
    Open this publication in new window or tab >>Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model
    Show others...
    2011 (English)In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, no 24, p. 1334-1350Article in journal (Refereed) Published
    Abstract [en]

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.

    National Category
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-164317 (URN)10.1152/physiolgenomics.00116.2011 (DOI)000298403600002 ()22010006 (PubMedID)
    Available from: 2011-12-19 Created: 2011-12-19 Last updated: 2017-12-08Bibliographically approved
    2. The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model
    Open this publication in new window or tab >>The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model
    Show others...
    2012 (English)In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 44, no 18, p. 865-877Article in journal (Refereed) Published
    Abstract [en]

    Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis for five days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of more than 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity and transcriptional regulation. Genes involved in the regulation of the oxidative stress response, cytoskeletal/sarcomeric and heat shock proteins were on the other hand down-regulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.

    Keywords
    Sepsis, porcine, muscle wasting, intensive care
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-180380 (URN)10.1152/physiolgenomics.00031.2012 (DOI)000309109100001 ()
    Available from: 2012-09-05 Created: 2012-09-05 Last updated: 2017-12-07Bibliographically approved
    3. Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model
    Open this publication in new window or tab >>Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model
    Show others...
    2013 (English)In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 45, no 8, p. 312-320Article in journal (Refereed) Published
    Abstract [en]

    Severe muscle wasting is a debilitating condition in critically ill intensive care unit (ICU) patients, characterized by general muscle weakness and dysfunction, resulting in a prolonged mobilization, delayed weaning from the ventilator and a decreased quality of life post-ICU. The mechanisms underlying limbmuscle weakness in ICU patients are complex and involve the impact of primary disease, but also factors common to critically ill ICU patients such as sepsis, mechanical ventilation (MV), immobilization and systemic administration of corticosteroids (CS).  These factors may have additive negative effects on skeletal muscle structure and function, but their respective role alone remain unknown. The primary aim of this study was to examine how CS administration potentiates ventilator and immobilization-related limb muscle dysfunction at the gene level. Comparing biceps femoris gene expression in pigs exposed to MV and CS for five days with only MV pigs for the same duration of time showed a distinct deregulation of 186 genes using microarray. Surprisingly, the decreased force-generation capacity at the single muscle fiber reported in response to the addition of CS administration in mechanically ventilated and immobilized pigs was not associated with an additional up-regulation of proteolytic pathways. On the other hand, an altered expression of genes regulating kinase activity, cell cycle, transcription, channel regulation, oxidative stress response , cytoskeletal, sarcomeric and heat shock protein as well as protein synthesis at the translational level appear to play an additive deleterious role for the  limb muscle weakness in immobilized ICU patients.

     

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-180375 (URN)10.1152/physiolgenomics.00123.2012 (DOI)000317662000002 ()23429211 (PubMedID)
    Available from: 2012-09-05 Created: 2012-09-05 Last updated: 2017-12-07Bibliographically approved
    4. Diaphragm muscle weakness in an experimental porcine intensive care unit model
    Open this publication in new window or tab >>Diaphragm muscle weakness in an experimental porcine intensive care unit model
    Show others...
    2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 6, article id e20558Article in journal (Refereed) Published
    Abstract [en]

    In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit.

    National Category
    Physiology
    Research subject
    Clinical Neurophysiology
    Identifiers
    urn:nbn:se:uu:diva-155622 (URN)10.1371/journal.pone.0020558 (DOI)000291730000014 ()21698290 (PubMedID)
    Available from: 2011-06-27 Created: 2011-06-27 Last updated: 2018-01-12Bibliographically approved
  • 33.
    Aarnio, Mikko
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Visualization of Peripheral Pain Generating Processes and Inflammation in Musculoskeletal Tissue using [11C]-D-deprenyl PET2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An objective visualization and quantification of pain-generating processes in the periphery would alter pain diagnosis and represent an important paradigm shift in pain research. Positron emission tomography (PET) radioligand [11C]-D-deprenyl has shown an elevated uptake in painful inflammatory arthritis and whiplash-associated disorder. However, D-Deprenyl’s molecular binding target and uptake mechanism in inflammation and musculoskeletal injuries are still unknown. The present thesis aimed to gain insight into the mechanisms of D-deprenyl binding and uptake and to verify whether pain-associated sites and inflammation in acute musculoskeletal injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET-computed tomography (PET/CT).

    To identify the D-deprenyl binding target, a high-throughput analysis and competitive radioligand binding studies were performed. D-deprenyl inhibited monoamine oxidase A (MAO-A) activity by 55%, MAO-B activity by 99% and angiotensin-converting enzyme (ACE) by 70%, which identified these enzymes as higher-affinity targets. Furthermore, radioligand receptor binding assays pointed favorably towards the concept of MAO-B as the primary target. To investigate the biochemical characteristics of the binding site, we used radioligand binding assays to assess differences in the binding profile in inflamed human synovial membranes exhibiting varying levels of inflammation. D-deprenyl bound to a single, saturable population of membrane-bound protein in synovial membrane homogenates and the level of inflammation correlated with an increase in D-deprenyl binding affinity.

    To verify whether D-deprenyl can visualize pain-generating processes, patients with musculoskeletal injuries were investigated and followed-up with [11C]-D-deprenyl PET/CT. In the study of eight patients with ankle sprain, the molecular aspects of inflammation and tissue injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. The pain coexisted with increased [11C]-D-deprenyl uptake. In the study of 16 whiplash patients, an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self-rated disability.

    To further evaluate D-Deprenyl’s usefulness as a marker of inflammation, three PET tracers were compared in an animal PET/CT study. Preliminary findings showed that [11C]-D-deprenyl had an almost identical uptake pattern when compared with [11C]-L-deprenyl. The two deprenyl enantiomers showed no signs of specific binding or trapping and therefore may not be useful to study further in models of inflammatory pain, surgical pain, or both.

    This thesis demonstrates that D-deprenyl visualizes painful inflammation in musculoskeletal injuries and that the probable underlying mechanism of [11C]-D-deprenyl uptake is binding to MAO.

    List of papers
    1. High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl
    Open this publication in new window or tab >>High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl
    Show others...
    2016 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 152, p. 231-237Article in journal (Refereed) Published
    Abstract [en]

    Aims: D-deprenyl is a useful positron emission tomography tracer for visualization of inflammatory processes. Studies with [C-11]-D-deprenyl showed robust uptake in peripheral painful sites of patients with rheumatoid arthritis or chronic whiplash injury. The mechanism of preferential D-deprenyl uptake is not yet known, but the existence of a specific binding site was proposed. Thus, in the present study, we sought to identify the binding site for D-deprenyl and verify the hypothesis about the possibility of monoamine oxidase enzymes as major targets for this molecule. Main methods: A high-throughput analysis of D-deprenyl activity towards 165 G-protein coupled receptors and 84 enzyme targets was performed. Additionally, binding studies were used to verify the competition of [H-3]D-deprenyl with ligands specific for targets identified in the high-throughput screen. Key findings: Our high-throughput investigation identified monoamine oxidase-B, monoamine oxidase-A and angiotensin converting enzyme as potential targets for D-deprenyl. Further competitive [3H] D-deprenyl binding studies with specific inhibitors identified monoamine oxidase-B as the major binding site. No evident high-affinity hits were identified among G-protein coupled receptors. Significance: Our study was the first to utilize a high-throughput screening approach to identify putative D-deprenyl targets. It verified 249 candidate proteins and confirmed the role of monoamine oxidase - B in D-deprenyl binding. Our results add knowledge about the possible mechanism of D-deprenyl binding, which might aid in explaining the increased uptake of this compound in peripheral inflammation. Monoamine oxidase-B will be further investigated in future studies utilizing human inflamed synovium.

    Keywords
    D-deprenyl High-throughput screening Binding site
    National Category
    Pharmaceutical Sciences Clinical Medicine
    Identifiers
    urn:nbn:se:uu:diva-291492 (URN)10.1016/j.lfs.2016.03.058 (DOI)000375728500028 ()27058977 (PubMedID)
    Funder
    Berzelii Centre EXSELENT, 2013-01495
    Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2018-04-09Bibliographically approved
    2. Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.
    Open this publication in new window or tab >>Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.
    Show others...
    2018 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 194, p. 26-33Article in journal (Refereed) Published
    Abstract [en]

    Aims: D-Deprenyl when used as a positron emission tomography tracer visualizes peripheral inflammation. The major aim of the current study was to identify and investigate the properties of the binding target for D-deprenyl in synovial membrane explants from arthritic patients.

    Main methods: Thirty patients diagnosed with arthritis or osteoarthritis were enrolled into the study. Homologous and competitive radioligand binding assays utilizing [H-3]D-deprenyl were performed to investigate the biochemical characteristics of the binding site and assess differences in the binding profile in synovial membranes exhibiting varying levels of inflammation.

    Key findings: The [H-3]D-deprenyl binding assay confirmed the existence of a single, saturable population of membrane-bound protein binding sites in synovial membrane homogenates. The macroscopically determined level of inflammation correlated with an increase in [H-3]D-deprenyl binding affinity, without significant alterations in binding site density. Selective monoamine oxidase B inhibitor, selegiline competed for the same site as [H-3]D-deprenyl, but failed to differentiate the samples with regard to their inflammation grade. A monoamine oxidase A inhibitor, pirlindole mesylate showed only weak displacement of [H-3]D-deprenyl binding. No significant alterations in monoamine oxidase B expression was detected, thus it was not confirmed whether it could serve as a marker for ongoing inflammation.

    Significance: Our study was the first to show the biochemical characteristics of the [H-3]D-deprenyl binding site in inflamed human synovium. We confirmed that d-deprenyl could differentiate between patients with varying severity of synovitis in the knee joint by binding to a protein target distinct from monoamine oxidase B.

    Keywords
    Arthritis, Binding target, Monoamine oxidase B, Synovium, d-Deprenyl
    National Category
    Pharmaceutical Sciences
    Research subject
    Pharmaceutical Biochemistry; Medical Biochemistry
    Identifiers
    urn:nbn:se:uu:diva-347601 (URN)10.1016/j.lfs.2017.12.003 (DOI)000425052000004 ()29221756 (PubMedID)
    Funder
    Swedish Research Council, 9459
    Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-18Bibliographically approved
    3. Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
    Open this publication in new window or tab >>Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
    Show others...
    2017 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, p. 418-424Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [(11)C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.

    METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [(11)C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.

    RESULTS: Acute [(11)C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [(11)C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [(11)C]-D-deprenyl uptake in painful locations.

    CONCLUSIONS AND IMPLICATIONS: The data provide further support that [(11)C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.

    Keywords
    Ankle injuries, Carbon-11, Deprenyl, Inflammation, PET, Pain
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-333782 (URN)10.1016/j.sjpain.2017.10.008 (DOI)000419851500070 ()29126847 (PubMedID)
    Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-04-09Bibliographically approved
    4. Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
    Open this publication in new window or tab >>Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The understanding of etiological mechanisms of whiplash associated disorder is still inadequate. Objective visualization and quantification of peripheral musculoskeletal injury and possible painful inflammation in whiplash associated disorder would facilitate diagnosis, strengthen patients’ subjective pain reports and aid clinical decisions eventually leading to better treatments. In the current study, we further evaluated the potential to use [11C]D-deprenyl PET/CT to visualize inflammation after whiplash injury. Sixteen patients with whiplash injury grade II were recruited at the emergency department and underwent [11C]D-deprenyl PET/CT in the acute phase and at 6 months after injury. Subjective pain levels, self rated neck disability and active cervical range of motion were recorded at each imaging session. Results showed that the molecular aspects of inflammation and possible tissue injuries after acute whiplash injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. An altered [11C]D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self rated disability during both imaging occasions. These findings may contribute to a better understanding of affected peripheral structures in whiplash injury and strengthens the idea that PET/CT detectable organic lesions in peripheral tissue may be relevant for the development of persistent pain and disability in whiplash injury.

    Perspective: This article presents a novel way of objectively visualizing possible structural damage and inflammation that cause pain and disability in whiplash injury. This PET method can bring an advance in pain research and eventually would facilitate the clinical management of patients in pain.

    Keywords
    Whiplash; deprenyl; inflammation; pain; PET; carbon-11
    National Category
    Medical and Health Sciences
    Research subject
    Molecular Medicine; Medical Cell Biology
    Identifiers
    urn:nbn:se:uu:diva-347602 (URN)
    Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-12
    5. Evaluation of  PET tracers [11C]D-deprenyl, [11C]L-dideuteriumdeprenyl and [18F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.
    Open this publication in new window or tab >>Evaluation of  PET tracers [11C]D-deprenyl, [11C]L-dideuteriumdeprenyl and [18F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: Positron emission tomography with the radioligand [11C]D-deprenyl has shown an increased signal at the location of pain in patients with ankle sprains, rheumatoid arthritis and chronic whiplash injury, but the mechanism of this tracer uptake and its exact binding site in inflammation or tissue injury is still unclear. The aim of this study was to further evaluate [11C]D-deprenyl´s usefulness as a marker of acute inflammation.

    Methods: An animal PET/CT study was performed three days after the induction of a rat model of inflammatory or surgical pain. Fourteen adult male Sprague-Dawley rats and three tracers [11C]D-deprenyl, [11C]L-dideuterumdeprenyl and [18F]fluorodeoxyglucose were used.

    Results: No [11C]D-deprenyl accumulation was seen in a rat model of musculoskeletal pain. In the rat model of inflammatory pain all three ligands were shown to visualize the inflamed ankle joint with much lower uptake in the control ankle joint. The uptake was largest with [11C]D-deprenyl and [11C]L- dideuteriumdeprenyl, where approximately 1 % of the injected dose could be found in the affected ankle joint during the first minutes, whereas the uptake of [18F]FDG was approximately 0.5 % of the injected dose. However, the ratio of uptake of the injected ankle joint versus the control ankle joint was much higher for [18F]FDG (around 10 fold increase) than for the two deprenyl enantiomers (2 – 3 fold increase). The uptake pattern of [11C]D-deprenyl and [11C]L-dideuteriumdeprenyl did not show signs of specific binding or irreversible trapping.

    Conclusions: Contrary to our expectations, of the three tracers only [18F]FDG may be used as markers of peripheral inflammation in a rat model of inflammatory pain. However, as a high site-specificity is required, [11C]D-deprenyl and [11C]L-dideyteriumdeprenyl deserve further exploration regarding sensitivity, specificity and uptake mechanisms in human pain syndromes.

    Keywords
    deprenyl; inflammation; pain; PET; carbon-11
    National Category
    Medical and Health Sciences
    Research subject
    Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-347604 (URN)
    Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-12
  • 34.
    Aarnio, Mikko
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Hall, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Ängeby-Möller, Kristina
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Evaluation of  PET tracers [11C]D-deprenyl, [11C]L-dideuteriumdeprenyl and [18F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.Manuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: Positron emission tomography with the radioligand [11C]D-deprenyl has shown an increased signal at the location of pain in patients with ankle sprains, rheumatoid arthritis and chronic whiplash injury, but the mechanism of this tracer uptake and its exact binding site in inflammation or tissue injury is still unclear. The aim of this study was to further evaluate [11C]D-deprenyl´s usefulness as a marker of acute inflammation.

    Methods: An animal PET/CT study was performed three days after the induction of a rat model of inflammatory or surgical pain. Fourteen adult male Sprague-Dawley rats and three tracers [11C]D-deprenyl, [11C]L-dideuterumdeprenyl and [18F]fluorodeoxyglucose were used.

    Results: No [11C]D-deprenyl accumulation was seen in a rat model of musculoskeletal pain. In the rat model of inflammatory pain all three ligands were shown to visualize the inflamed ankle joint with much lower uptake in the control ankle joint. The uptake was largest with [11C]D-deprenyl and [11C]L- dideuteriumdeprenyl, where approximately 1 % of the injected dose could be found in the affected ankle joint during the first minutes, whereas the uptake of [18F]FDG was approximately 0.5 % of the injected dose. However, the ratio of uptake of the injected ankle joint versus the control ankle joint was much higher for [18F]FDG (around 10 fold increase) than for the two deprenyl enantiomers (2 – 3 fold increase). The uptake pattern of [11C]D-deprenyl and [11C]L-dideuteriumdeprenyl did not show signs of specific binding or irreversible trapping.

    Conclusions: Contrary to our expectations, of the three tracers only [18F]FDG may be used as markers of peripheral inflammation in a rat model of inflammatory pain. However, as a high site-specificity is required, [11C]D-deprenyl and [11C]L-dideyteriumdeprenyl deserve further exploration regarding sensitivity, specificity and uptake mechanisms in human pain syndromes.

  • 35.
    Aarnio, Mikko
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wolf, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Peterson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Linnman, Clas
    Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.2017In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, p. 418-424Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [(11)C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.

    METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [(11)C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.

    RESULTS: Acute [(11)C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [(11)C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [(11)C]-D-deprenyl uptake in painful locations.

    CONCLUSIONS AND IMPLICATIONS: The data provide further support that [(11)C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.

  • 36.
    Aarnio, Mikko
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Linnman, Clas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Gordh, Torsten
    Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CTManuscript (preprint) (Other academic)
    Abstract [en]

    The understanding of etiological mechanisms of whiplash associated disorder is still inadequate. Objective visualization and quantification of peripheral musculoskeletal injury and possible painful inflammation in whiplash associated disorder would facilitate diagnosis, strengthen patients’ subjective pain reports and aid clinical decisions eventually leading to better treatments. In the current study, we further evaluated the potential to use [11C]D-deprenyl PET/CT to visualize inflammation after whiplash injury. Sixteen patients with whiplash injury grade II were recruited at the emergency department and underwent [11C]D-deprenyl PET/CT in the acute phase and at 6 months after injury. Subjective pain levels, self rated neck disability and active cervical range of motion were recorded at each imaging session. Results showed that the molecular aspects of inflammation and possible tissue injuries after acute whiplash injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. An altered [11C]D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self rated disability during both imaging occasions. These findings may contribute to a better understanding of affected peripheral structures in whiplash injury and strengthens the idea that PET/CT detectable organic lesions in peripheral tissue may be relevant for the development of persistent pain and disability in whiplash injury.

    Perspective: This article presents a novel way of objectively visualizing possible structural damage and inflammation that cause pain and disability in whiplash injury. This PET method can bring an advance in pain research and eventually would facilitate the clinical management of patients in pain.

  • 37.
    Aarnio, Pauliina
    et al.
    Univ Tampere, Fac Social Sci Global Hlth & Dev, Kalevantie 4, FI-33014 Tampere, Finland;Univ Tampere, Med Sch, Dept Int Hlth, Tampere, Finland.
    Kulmala, Teija
    Univ Tampere, Med Sch, Child Hlth Res Unit, Tampere, Finland;Univ Tampere, Med Sch, Dept Int Hlth, Tampere, Finland.
    Olsson, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Husband's role in handling pregnancy complications in Mangochi District, Malawi: A call for increased focus on community level male involvement2018In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 16, p. 61-66Article in journal (Refereed)
    Abstract [en]

    Objective: The objective of the current study is to provide information about husbands' role in decision-making and healthcare seeking in cases of pregnancy complications in Mangochi district, Malawi with an analysis of qualitative interviews using the concepts of "capital" and "field" from Bourdieu's social field theory. Study design: Twelve husbands and wives who had experienced pregnancy complications and six key informants from a semi-rural area of Mangochi district were interviewed individually. Thematic analysis was conducted based on the concepts of capital and field in Bourdieu's social field theory. Results: Husbands have significant economic and symbolic capital in decisions about healthcare seeking during instances of pregnancy complications as a result of their roles as father, head of the household and main income earner. Lack of money is the only acceptable reason for husbands to deny their wives healthcare. Husbands have limited access to knowledge of maternal health, which can compromise their decisions about seeking healthcare. Joint decision-making within families can be bypassed to allow for prompt healthcare seeking in emergencies. Conclusions: Husbands are important decision makers regarding seeking healthcare for pregnancy complications because of their economic and symbolic power and despite their limited access to knowledge of maternal health. Maternal healthcare seeking practices would benefit from wives gaining an empowered role as well as improved knowledge of maternal health among husbands.

  • 38.
    Aarnio, Pauliina