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  • 1.
    Anan, Intissar
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    El-Salhy, M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Y
    Nyhlin, N
    Terazaki, H
    Sakashita, N
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Colonic endocrine cells in patients with familial amyloidotic polyneuropathy.1999In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 245, no 5, p. 469-73Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To establish whether the endocrine cell number is affected in the colon in Japanese FAP patients.

    SETTING: Department of Medicine, Umeå University Hospital and Department of Internal Medicine and Pathology, University Hospital, Kumamoto, Japan.

    SUBJECTS: Autopsy colon tissue specimens from 11 FAP patients and nine controls as well as 12 control biopsy specimens were included in the study.

    MEASUREMENTS: Endocrine cells in the colon were detected by immunohistochemistry and quantified by computerized image analysis.

    RESULTS: The autopsy material showed a slight autolysis. Neither enteroglucagon nor pancreatic polypeptide positive cells could be detected in the autopsy material, but were present in biopsy material. There was no statistical difference between autopsy and biopsy specimens regarding the number of peptide YY (PYY), somatostatin and serotonin cells. No significant differences were noted in PYY, somatostatin and serotonin immunoreactive cells in FAP patients compared to autopsy controls, though PYY cells tended to be decreased and serotonin and somatostatin cells tended to be increased in FAP patients.

    CONCLUSION: The difference between the Swedish and Japanese patients in the endocrine cell content points to the possibility of involvement of other factors than the endocrine cell depletion of the colon might be involved in the pathogenesis of gastro-intestinal dysfunction in FAP. The tendency of PYY to decrease in Japanese FAP might contribute to the development of diarrhoea in these patients.

  • 2.
    Andersson, Christer
    et al.
    Primary Health Care Centre, Arjeplog.
    Bjersing, Lars
    Lithner, Folke
    The epideimiology of hepatocellular carcinoma in patients with acute intermittent porphyria1996In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 240, no 4, p. 195-201Article in journal (Refereed)
    Abstract

    Objective. To describe the epidemiology, pathogenesis and clinical features of hepatocellular carcinoma (HCC) in patients with acute intermittent porphyria (AIP).

    Design. A retrospective population-based mortality study.

    Subjects. All inhabitants who died between 1978–1990 (2122) including 33 with AIP, in two municipalities in northern Sweden with a high prevalence of AIP.

    Interventions. Death certificates and hospital records were examined. Histological re-examination of paraffin-embedded specimens from patients with HCC was performed and hepatitis B virus content analysed.

    Results. HCC was found in 27% of patients with AIP versus 0.2% of the deceased non-AIP subjects, P< 0.0001. HCC was more common in women (men:women 1:2) and in manifest AIP (manifest: latent 2:1). Liver cirrhosis was more common in AIP patients (12%), especially in women, compared with controls (0.5%), P<0.0001.

    Conclusions. AIP patients seem to have an increased risk of developing HCC. This tumour is more common in patients with manifest AIP and in women, a reversal of the usually reported gender ratio for HCC. No cause for developing HCC other than AIP was found. The pathogenesis may be explained by abnormalities in porphyrin metabolism and by intrinsic production of mutagenic substances, resulting in a condition of systemic overload of oxidative stress, enhancing mutation rate and liver cell injury. Liver cirrhosis appears to be more common in AIP patients and may be a preliminary stage to HCC. All AIP gene carriers aged 55 should be screened for HCC.

  • 3.
    Andersson, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Innala, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in northern Sweden2003In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 254, no 2, p. 176-183Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe the clinical expression of acute intermittent porphyria (AIP) in women, their use of exogenous sex hormones, and the effects on AIP. DESIGN: A retrospective population-based study. SUBJECTS: All women aged > or =18 years (n = 190) with DNA-diagnosed AIP in northern Sweden. RESULTS: A total of 166 women (87%) participated; 91 (55%) had manifest AIP. Severe attacks were reported by 82%; 39% reported recurrent premenstrual AIP attacks and 22% reported chronic AIP symptoms. Oral hormonal contraceptives had been used by 58% of all these women and by 50 with manifest AIP (57%). Twelve women (24%) associated oral contraceptives as precipitating AIP attacks; in nine cases their first attack. One woman experienced relief from AIP symptoms. On commencing their treatment, 72% of the women with manifest AIP had not yet suffered their first attack. Twenty-two women (25%) aged > or =45 years had used hormonal replacement therapy (HRT) at menopause to remedy climacteric symptoms (the percutaneous route was most frequently used); no AIP attack was precipitated. HRT to remedy vaginal dryness was used by 26 women (28%) aged > or =45 years without triggering an AIP attack. Miscarriages were more frequent in women with manifest AIP (50%) than in the latent group (30%, P = 0.014). CONCLUSIONS: About half of the women with AIP had used oral hormonal contraceptives. As 25% of women with manifest AIP reported attacks associated with such drugs, caution must still be recommended. Menopausal HRT only rarely affected the disorder. Miscarriage was more common amongst women with manifest AIP.

  • 4.
    Andersson, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Lithner, F.
    Umeå University, Faculty of Medicine.
    Hypertension and renal impairment in patients with acute intermittent porphyria: a populaition-based study1994In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 236, no 2, p. 169-175Article in journal (Refereed)
    Abstract [en]

    Objectives: To assess the association between acute intermittent porphyria (AIP), hypertension and renal disease.

    Design: A population-based matched case-control study (1:4) in 50 AIP patients (manifest/latent 25/25), a retrospective study of all individuals who died between the years 1978 and 1990 (2122 including 33 with AIP) and a group of eight patients with severe AIP.

    Results: Hypertension was found in 56% of patients with manifest AIP, 33% of their controls (P = 0.041) and 16% of patients with latent AIP (P = 0.004). Renal disease was not more common in patients with AIP than in their controls. Three of the eight patients with severe recurrent AIP had impaired renal function, caused in one by systemic lupus erythematosus (SLE) nephritis. In the other two, no cause other than AIP could be found. In the mortality study, hypertension was registered in 68% of patients with manifest AIP compared to 21% of those with latent AIP (P = 0.008) but death from myocardial infarction and stroke was not more common. Uraemia was cited as the cause of death in 9.1% of AIP patients and 1.0% of those without AIP (P = 0.006).

    Conclusions: Hypertension is more common in patients with manifest AIP than in those with latent AIP or control subjects. Renal disease may be due to hypertension, to AIP or to SLE. AIP may predispose to other renal diseases.

  • 5.
    Andersson, Christer
    et al.
    Umeå University, Faculty of Medicine.
    Lithner, Folke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Hypertension and renal disease in patients with acute intermitent porphyria1994In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 236, p. 169-175Article in journal (Refereed)
  • 6.
    Andersson, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Nilsson, T.
    From the Primary Health Care Centre, Arvidsjaur, Sweden, .
    Bäckström, Torbjörn
    Atypical attack of acute intermittent porphyria: paresis but not abdominal pain2002In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 252, no 3, p. 265-270Article in journal (Refereed)
    Abstract [en]

    We report a case of acute intermittent porphyria (AIP) in a 45-year-old woman. Her first attack occurred at the age of 38. Because of escalating cyclical premenstrual attacks, the following 2 years, depletion of the endogenous sex hormone was considered as haeme arginate treatment proved insufficient. Gonadotropin releasing hormone agonist treatment with low-dose oestradiol add back was quite successful initially but was abandoned after 18 months when progesterone add back precipitated a severe attack. Following hysterectomy and oophorectomy at age 42 and oestradiol add back, a remarkable monthly regularity of attacks ensured periodically but with milder symptoms. Two years after surgery, preceded by six attack-free months, a puzzling symptom-shift occurred, from abdominal pain, back and thigh pain during the attacks, to solely severe distal extensor paresis in the arms. Haeme arginate treatment interrupted the progress of the paresis almost immediately and motor function improved considerably up to the 9-month follow-up. Electrophysiological examination revealed only motor neuropathy, consistent with axonal degeneration. Subsequently the symptoms changed yet again, to sensory disturbances with numbness and dysesthesia as the primary expression followed by rather mild abdominal pain. However, cyclical attacks occurred, despite absence of endogenous ovarial hormone production, possibly attributable to impaired oestrogen metabolism in the liver, or adrenal oestrogen production. Treatment comprising oophorectomy, low-dose oestradiol add back and haeme arginate infusion for 2 days on the appearance of early AIP symptoms is now quite successful affording improvement in life quality.

  • 7.
    Andersson, Christer
    et al.
    Umeå University, Faculty of Medicine.
    Wikberg, Agneta
    Lithner, Folke
    Signs of neuropathy in lower legs and feet of patients with acute intermittent porphyria2000In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 248, p. 27-32Article in journal (Refereed)
  • 8.
    Andersson, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Wikberg, Agneta
    Umeå University, Faculty of Medicine, Department of Nursing.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lithner, Folke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Renal symtomatology in patients with acute intermitent porphyria2000In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 248, p. 319-325Article in journal (Refereed)
    Abstract [en]

    Objective: Can renal insufficiency in subjects with acute intermittent porphyria (AIP) be due solely to AIP?

    Design: A population-based study.

    Subjects: Subjects with AIP ≥ 18 years of age (n = 386) in the four most northerly counties of Sweden.

    Interventions: Screening with creatinine clearance at 24 h. Patients below the lower reference level underwent a repeat clearance test and, if still low, also chromEDTA clearance.

    Results: 286 (74%) subjects performed the creatinine clearance test and in 57 clearance was low; the second clearance proved normal in 23 who were then excluded. Eighteen subjects with other possible medical reasons for renal insufficiency, ethical reasons or refusing further examinations were also excluded. The 16 remaining subjects with no explanation for their renal insufficiency other than AIP were then studied in detail. All 14 women, mean age 52 years, and two uraemic men, 58 and 67 years, had manifest AIP. Twelve patients had hypertension (HT) and four were normotensive in spite of renal insufficiency. Histological findings of renal biopsies revealed diffuse glomerulosclerotic and interstitial changes with additional ischaemic lesions.

    Conclusion: Protracted vasospasm in attacks of AIP may be a cause of renal lesions. This is discussed.

  • 9.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The controversial snuff2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 276, no 1, p. 74-76Article in journal (Other academic)
  • 10. Bamia, C
    et al.
    Halkjaer, J
    Lagiou, P
    Trichopoulos, D
    Tjønneland, A
    Berentzen, T L
    Overvad, K
    Clavel-Chapelon, F
    Boutron-Ruault, M-C
    Rohrmann, S
    Linseisen, J
    Steffen, A
    Boeing, H
    May, A M
    Peeters, P H
    Bas Bueno-de-Mesquita, H
    van den Berg, S W
    Dorronsoro, M
    Barricarte, A
    Rodriguez Suarez, L
    Navarro, C
    González, C A
    Boffetta, P
    Pala, V
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Trichopoulou, A
    Weight change in later life and risk of death amongst the elderly: the European Prospective Investigation into Cancer and Nutrition-Elderly Network on Ageing and Health study2010In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 268, no 2, p. 133-144Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Later life weight change and mortality amongst elders. DESIGN: Nested case-control study. SETTING: Six countries from the European Investigation into Cancer and nutrition-Elderly, Network on Ageing and Health. SUBJECTS: A total of 1712 deceased (cases) and 4942 alive (controls) were selected from 34,239 participants, > or = 60 years at enrolment (1992-2000) who were followed-up until March 2007. Annual weight change was estimated as the weight difference from recruitment to the most distant from-date-of-death re-assessment, divided by the respective time. OUTCOME MEASURES: Mortality in relation to weight change was examined using conditional logistic regression. RESULTS: Weight loss > 1 kg year(-1) was associated with statistically significant increased death risk (OR = 1.65; 95% CI: 1.41-1.92) compared to minimal weight change (+/-1 kg year(-1)). Weight gain > 1 kg year(-1) was also associated with increased risk of death (OR = 1.15; 95% CI: 0.98-1.37), but this was evident and statistically significant only amongst overweight/obese (OR = 1.55; 95% CI: 1.17-2.05). In analyses by time interval since weight re-assessment, the association of mortality with weight loss was stronger for the interval proximal (< 1 year) to death (OR = 3.10; 95% CI: 2.03-4.72). The association of mortality with weight gain was stronger at the interval of more than 3 years and statistically significant only amongst overweight/obese (OR = 1.58; 95% CI: 1.07-2.33). Similar patterns were observed regarding death from circulatory diseases and cancer. CONCLUSIONS: In elderly, stable body weight is a predictor of lower subsequent mortality. Weight loss is associated with increased mortality, particularly short-term, probably reflecting underlying nosology. Weight gain, especially amongst overweight/obese elders, is also associated with increased mortality, particularly longer term.

  • 11. Bergström, G
    et al.
    Berglund, G
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Brandberg, J
    Engström, G
    Engvall, J
    Eriksson, M
    de Faire, U
    Flinck, A
    Hansson, M G
    Hedblad, B
    Hjelmgren, O
    Janson, C
    Jernberg, T
    Johnsson, Å
    Johansson, L
    Lind, L
    Löfdahl, C-G
    Melander, O
    Östgren, C J
    Persson, A
    Persson, M
    Sandström, Anette
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schmidt, C
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sundström, J
    Toren, K
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Thoracic Center, Umeå University Hospital.
    Wedel, H
    Vikgren, J
    Fagerberg, B
    Rosengren, A
    The Swedish CArdioPulmonary BioImage Study: objectives and design.2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, no 6, p. 645-659Article in journal (Refereed)
    Abstract [en]

    Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

  • 12. Beulens, J. W. J.
    et al.
    van der Schouw, Y. T.
    Bergmann, M. M.
    Rohrmann, S.
    Schulze, M. B.
    Buijsse, B.
    Grobbee, D. E.
    Arriola, L.
    Cauchi, S.
    Tormo, M-J
    Allen, N. E.
    van der A, D. L.
    Balkau, B.
    Boeing, H.
    Clavel-Chapelon, F.
    de Lauzon-Guillan, B.
    Franks, P.
    Froguel, P.
    Gonzales, C.
    Halkjaer, J.
    Huerta, J. M.
    Kaaks, R.
    Key, T. J.
    Khaw, K. T.
    Krogh, V.
    Molina-Montes, E.
    Nilsson, P.
    Overvad, K.
    Palli, D.
    Panico, S.
    Ramón Quirós, J.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Romieu, I.
    Romaguera, D.
    Sacerdote, C.
    Sánchez, M-J
    Spijkerman, A. M. W.
    Teucher, B.
    Tjonneland, A.
    Tumino, R.
    Sharp, S.
    Forouhi, N. G.
    Langenberg, C.
    Feskens, E. J. M.
    Riboli, E.
    Wareham, N. J.
    Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body size The EPIC-InterAct study2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 272, no 4, p. 358-370Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. Design: Multicentre prospective casecohort study. Setting: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. Subjects: A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes. Interventions: Alcohol consumption assessed using validated dietary questionnaires. Main outcome measures: Occurrence of type 2 diabetes based on multiple sources (mainly self-reports), verified against medical information. Results: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.781.05) for 6.112.0 versus 0.16.0 g day-1, adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.196.0 g day-1 with an HR of 0.86 (95% CI: 0.750.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.720.92) for 6.112.0 g day-1 (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI = 25 kg m-2) than normal-weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.791.03 for 6.112.0 g day-1). Wine consumption for men and fortified wine  consumption for women were most strongly associated with a reduced risk of diabetes. Conclusions: The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal-weight women and men.

  • 13. Bjarnsholt, T.
    et al.
    Buhlin, K.
    Dufrêne, Y. F.
    Gomelsky, M.
    Moroni, A.
    Ramstedt, Madeleine
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Rumbaugh, K. P.
    Schulte, T.
    Sun, L.
    Åkerlund, B.
    Römling, U.
    Biofilm formation – what we can learn from recent developments2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 284, no 4, p. 332-345Article in journal (Refereed)
    Abstract [en]

    Although biofilms have been observed early in the history of microbial research, their impact has only recently been fully recognized. Biofilm infections, which contribute to up to 80% of human microbial infections, are associated with common human disorders, such as diabetes mellitus and poor dental hygiene, but also with medical implants. The associated chronic infections such as wound infections, dental caries and periodontitis significantly enhance morbidity, affect quality of life and can aid development of follow-up diseases such as cancer. Biofilm infections remain challenging to treat and antibiotic monotherapy is often insufficient, although some rediscovered traditional compounds have shown surprising efficiency. Innovative anti-biofilm strategies include application of anti-biofilm small molecules, intrinsic or external stimulation of production of reactive molecules, utilization of materials with antimicrobial properties and dispersion of biofilms by digestion of the extracellular matrix, also in combination with physical biofilm breakdown. Although basic principles of biofilm formation have been deciphered, the molecular understanding of the formation and structural organization of various types of biofilms has just begun to emerge. Basic studies of biofilm physiology have also resulted in an unexpected discovery of cyclic dinucleotide second messengers that are involved in interkingdom crosstalk via specific mammalian receptors. These findings even open up new venues for exploring novel anti-biofilm strategies.

  • 14.
    Carlberg, B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hägg, E
    High blood pressure in acute stroke--is it white coat hypertension?1990In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 228, no 3, p. 291-2Article in journal (Refereed)
  • 15. Carlsson, S
    et al.
    Andersson, T
    Araghi, M
    Galanti, R
    Lager, A
    Lundberg, M
    Nilsson, P
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Pedersen, N L
    Trolle-Lagerros, Y
    Magnusson, C
    Smokeless tobacco (snus) is associated with an increased risk of type 2 diabetes: results from five pooled cohorts2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 4, p. 398-406Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Smoking and nicotine exposure increase insulin resistance and the risk of type 2 diabetes. Swedish smokeless tobacco (snus) is high in nicotine, and its use is prevalent in Scandinavian countries, but few studies have investigated snus use in relation to diabetes risk.

    OBJECTIVE: To explore the association between snus use and risk of type 2 diabetes using pooled data from five cohorts.

    METHODS: Analyses were based on prospective studies conducted between 1990 and 2013 including 54 531 never-smoking men and 2441 incident cases of type 2 diabetes identified through screening, self-reporting and hospital and prescription registries. Hazard ratios (HRs) and 95% confidence intervals (CIs) were assessed and adjusted for age, body mass index, educational level, alcohol consumption and physical activity.

    RESULTS: Compared to never users, the HR of type 2 diabetes was 1.15 (95% CI: 1.00-1.32) in current users of snus. In individuals consuming 5-6 boxes per week, the HR was 1.42 (95% CI: 1.07-1.87); in those consuming ≥7 boxes per week, the HR was 1.68 (95% CI: 1.17-2.41). Each additional box of snus consumed per week yielded an HR of 1.08 (95% CI: 1.01-1.16).

    CONCLUSION: Our findings indicate that high consumption of snus is a risk factor for type 2 diabetes. The risk was similar to that in smokers, implying that smokers will not reduce their risk of type 2 diabetes by changing to snus use. The results also support the notion that nicotine increases the risk of type 2 diabetes.

  • 16.
    Claesson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Birgander, Lisbeth Slunga
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jansson, Jan-Håkan
    Lindahl, B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Burell, G
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mattsson, Cecilia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cognitive-behavioural stress management does not improve biological cardiovascular risk indicators in women with ischaemic heart disease: a randomized-controlled trial.2006In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 260, no 4, p. 320-331Article in journal (Refereed)
  • 17. Coca-Prieto, Inmaculada
    et al.
    Kroupa, Olessia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Gonzalez-Santos, Pedro
    Magne, Joëlle
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Ehrenborg, Ewa
    Valdivielso, Pedro
    Childhood-onset chylomicronaemia with reduced plasma lipoprotein lipase activity and mass: identification of a novel GPIHBP1 mutation2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 3, p. 224-228Article in journal (Refereed)
    Abstract [en]

    Objectives:  Deficiency in the catabolism of triglyceride-rich lipoproteins is the main cause of childhood-onset chylomicronaemia syndrome. Missense mutations in lipoprotein lipase (LPL) or in proteins influencing LPL activity or stability have been shown to be critical determinants of chylomicronaemia syndrome. The main objective of the present study was to assess the primary deficiency in five cases of childhood-onset chylomicronaemia syndrome.

    Setting:  Lipid clinic at a university hospital,

    Subjects:  Subjects presenting with severe hypertriglyceridaemia and chylomicronaemia syndrome in which reduced LPL activity and mass was observed. Interventions:  Analysis of LPL and GPIHBP1 genes.

    Results:  Among the five patients, one novel homozygous missense mutation (p.C68Y) in exon 3 of GPIHBP1 was identified. The other four patients were homozygous for the common LPL mutation p.G188E.

    Conclusion:  These findings provide further evidence that GPIHBP1 is involved in the catabolism of triglyceride-rich lipoproteins and plays a role in childhood-onset chylomicronaemia.

  • 18. Cornelis, M. C.
    et al.
    Gustafsson, S.
    Arnlov, J.
    Elmstahl, S.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sundstrom, J.
    Michaelsson, K.
    Lind, L.
    Ingelsson, E.
    Targeted proteomic analysis of habitual coffee consumption2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 2, p. 200-211Article in journal (Refereed)
    Abstract [en]

    Background: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large‐scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.

    Objective: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418).

    Methods: In PIVUS and ULSAM, coffee intake was measured by 7‐day dietary records whilst a computer‐based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.

    Results: Four protein–coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10−3): leptin (LEP), chitinase‐3‐like protein 1 (CHI3L), tumour necrosis factor (TNF) receptor 6 and TNF‐related apoptosis‐inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, −0.042 SD per cup of coffee, P = 0.028) and EpiHealth (β, −0.025 SD per time of coffee, P = 0.004). The negative coffee–CHI3L association replicated in EpiHealth (β, −0.07, P = 1.15 × 10−7), but not in ULSAM (β, −0.034, P = 0.16).

    Conclusions: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee–CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.

  • 19. Eriksson, D
    et al.
    Bianchi, M
    Landegren, N
    Nordin, J
    Dalin, F
    Mathioudaki, A
    Eriksson, G N
    Hultin-Rosenberg, L
    Dahlqvist, J
    Zetterqvist, H
    Karlsson, Å
    Hallgren, Å
    Farias, F H G
    Murén, E
    Ahlgren, K M
    Lobell, A
    Andersson, G
    Tandre, K
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Söderkvist, P
    Rönnblom, L
    Hulting, A-L
    Wahlberg, J
    Ekwall, O
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Meadows, J R S
    Bensing, S
    Lindblad-Toh, K
    Kämpe, O
    Pielberg, G R
    Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 6, p. 595-608Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.

    METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.

    RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.

    CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

  • 20. Eriksson, J W
    et al.
    Carlberg, Bpo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hillörn, Valter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Life-threatening ventricular tachycardia due to liquorice-induced hypokalaemia.1999In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 245, no 3, p. 307-10Article in journal (Refereed)
    Abstract [en]

    We report on a patient with hypokalaemia and severe ventricular tachycardia of torsades de pointes type which turned out to be caused by an apparent mineralocorticoid excess syndrome associated with liquorice consumption. The patient, a 44-year-old woman, attended the hospital because of irregular heart rhythm and she displayed repeated episodes of life-threatening torsades de pointes ventricular tachycardia. The initial serum potassium was low: 2.3 mmol L-1. The patient was treated with potassium and magnesium infusions, and the dysrhythmias eventually ceased. Endocrinological investigations showed no indication of Cushing's syndrome or hyperaldosteronism. After some time it became clear that the patient had ingested moderately large amounts of liquorice every day for 4 months. After the patient stopped this habit the hypokalaemia and dysrhythmias did not recur and after more than 1 year there are no signs of cardiac illness.

  • 21.
    Eriksson, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Holmgren, L.
    Janlert, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Skellefteå Hospital, Skellefteå.
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Sunderby Hospital, Luleå.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. National Board of Health and Welfare, Stockholm.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Sunderby Hospital, Luleå.
    Large improvements in major cardiovascular risk factors in the population of northern Sweden: the MONICA study 1986–20092011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 2, p. 219-231Article in journal (Refereed)
    Abstract [en]

    Objectives. The incidence of cardiovascular disease has declined rapidly in Sweden since the 1980s. We explored changes in major cardiovascular risk factors in northern Sweden between 1986 and 2009.

    Design. Since 1986, six population surveys have been carried out in northern Sweden using procedures of the World Health Organization MONICA project. The population age range was 25–64 years in 1986 and 1990, and 25–74 years from 1994. Trends were analysed using generalized linear models.

    Results. A total of 10 586 subjects were included in the surveys. Blood pressure decreased by 4.9/3.9 mmHg in women and 1.8/1.5 mmHg in men aged 25–64 years between 1986 and 2009. In men and women aged 65–74 years, the decrease was 12.6/6.1 mmHg between 1994 and 2009. From 1994, the use of blood pressure‐lowering drugs increased, particularly among the older subgroup. The prevalence of smoking halved between 1986 and 2009; 11% of women and 9% of men were smokers in 2009. Cholesterol levels decreased by 0.9 mmol L−1 in the younger age group (25–64 years), and the use of lipid‐lowering agents increased from 1994. Among subjects aged 25–64 years, one in five was obese in 2009, which was twice as many as in 1986, and body mass index (BMI) increased by 1.5 kg m−2, corresponding to an increase in weight of 4 kg. There was no further increase in BMI from 2004. The prevalence of diabetes did not change between 1986 and 2009. The proportion that received a university education increased markedly in all age groups, especially in women, during the study period.

    Conclusions. Significant improvements were observed in major cardiovascular risk factors in northern Sweden between 1986 and 2009.

  • 22.
    Franks, P. W.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Genetic & Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University Diabetes Center, Skåne University Hospital, Malmö; Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
    Atabaki-Pasdar, N.
    Causal inference in obesity research2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 3, p. 222-232Article, review/survey (Refereed)
    Abstract [en]

    Obesity is a risk factor for a plethora of severe morbidities and premature death. Most supporting evidence comes from observational studies that are prone to chance, bias and confounding. Even data on the protective effects of weight loss from randomized controlled trials will be susceptible to confounding and bias if treatment assignment cannot be masked, which is usually the case with lifestyle and surgical interventions. Thus, whilst obesity is widely considered the major modifiable risk factor for many chronic diseases, its causes and consequences are often difficult to determine. Addressing this is important, as the prevention and treatment of any disease requires that interventions focus on causal risk factors. Disease prediction, although not dependent on knowing the causes, is nevertheless enhanced by such knowledge. Here, we provide an overview of some of the barriers to causal inference in obesity research and discuss analytical approaches, such as Mendelian randomization, that can help to overcome these obstacles. In a systematic review of the literature in this field, we found: (i) probable causal relationships between adiposity and bone health/disease, cancers (colorectal, lung and kidney cancers), cardiometabolic traits (blood pressure, fasting insulin, inflammatory markers and lipids), uric acid concentrations, coronary heart disease and venous thrombosis (in the presence of pulmonary embolism), (ii) possible causal relationships between adiposity and gray matter volume, depression and common mental disorders, oesophageal cancer, macroalbuminuria, end-stage renal disease, diabetic kidney disease, nuclear cataract and gall stone disease, and (iii) no evidence for causal relationships between adiposity and Alzheimer's disease, pancreatic cancer, venous thrombosis (in the absence of pulmonary embolism), liver function and periodontitis.

  • 23.
    Glader, Eva-Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norrving, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Terent, Andreas
    Department of Clinical Neuroscience, Lund University, Lund, Sweden.
    Hulter-Åsberg, Kerstin
    Department of Medical Science, Uppsala University, Uppsala, Sweden.
    Wester, P.-O.
    Department of Medicine, Enköping Hospital, Enköping, Sweden.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Large variations in the use of oral anticoagulants in stroke patients with atrial fibrillation: A Swedish national perspective2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 255, no 1, p. 22-32Article in journal (Refereed)
    Abstract [en]

    Objectives. To explore nation-wide use of anticoagulation in stroke patients with atrial fibrillation, in routine clinical practice in Sweden.

    Design.  Cross-sectional cohort study.

    Setting. Patients included in Riks-Stroke, the Swedish national quality register for stroke care, during 2001.

    Subjects. Hospitals with incomplete coverage were excluded, leaving 4538 stroke patients with atrial fibrillation amongst 18 276 stroke patients from 75 hospitals in six health care regions.

    Main outcome measure.  Treatment with oral anticoagulants.

    Results. At stroke onset, the proportion of patients with atrial fibrillation and first-ever stroke, receiving oral anticoagulants as primary prevention was 11.0% (range 8.4–13.5% between regions and 2.5–24.4% between hospitals). Younger age, male sex and diabetes at stroke onset independently predicted primary prevention with oral anticoagulants. The proportion of stroke patients with atrial fibrillation receiving oral anticoagulants as secondary prevention at discharge was 33.5% (range 29.9–40.6% between regions and 16.4–61.9% between hospitals). Independent predictors for secondary prevention were younger age, male sex and independent activities of daily life (ADL) function before the stroke, being discharged to home, being fully conscious on admission and health care region.

    Conclusion.  There were variations between hospitals and regions that differences in age, sex, functional impairments and comorbidities could not fully explain. This indicates that evidence-based primary and secondary prevention of embolic stroke is insufficiently practised. Local factors seem to determine whether patients with atrial fibrillation gain access to optimal prevention of stroke or not.

  • 24. Gräns, Hanna
    et al.
    Nilsson, P
    Evengård, Birgitta
    From the Departments of Clinical Bacteriology, Karolinska Institutet, Karolinska University Hospital, Huddinge.
    Gene expression profiling in the chronic fatigue syndrome2005In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 258, no 4, p. 388-390Article in journal (Refereed)
  • 25. Hansson, Jenny
    et al.
    Galanti, Maria Rosaria
    Hergens, Maria-Pia
    Fredlund, Peeter
    Ahlbom, Anders
    Alfredsson, Lars
    Bellocco, Rino
    Engström, Gunnar
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Hallqvist, Johan
    Hedblad, Bo
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pedersen, Nancy L
    Lagerros, Ylva Trolle
    Östergren, Per-Olof
    Magnusson, Cecilia
    Snus (Swedish smokeless tobacco) use and risk of stroke: Pooled Analyses of Incidence and Survival2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 276, no 1, p. 87-95Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Snus is a moist smokeless tobacco product with a high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear.

    OBJECTIVE: The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes.

    METHODS: Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130 485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models, and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively.

    RESULTS: No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) among users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61).

    CONCLUSION: Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared to non-users, but further studies are needed to determine any possible causal mechanisms.

  • 26.
    Holmqvist, ME
    et al.
    Institute of Environmental Medicine, Karolinska Institutet.
    Wedren, S
    Institute of Environmental Medicine, Karolinska Institutet.
    Jacobsson, LTH
    Rheumatology Unit, Department of Medicine, Malmö University Hospital, Malmö.
    Klareskog, L
    Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska Hospital, Stockholm.
    Nyberg, F
    Institute of Environmental Medicine, Karolinska Institutet.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Alfredsson, L
    Institute of Environmental Medicine, Karolinska Institutet.
    Askling, J
    Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska Hospital, Stockholm.
    Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 20062010In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 268, no 6, p. 578-585Article in journal (Refereed)
    Abstract [en]

    Holmqvist ME, Wedren S, Jacobsson LTH, Klareskog L, Nyberg F, Rantapaa-Dahlqvist S, Alfredsson L, Askling J (Institute of Environmental Medicine, Karolinska Institutet, Stockholm; Karolinska Institutet/Karolinska Hospital, Stockholm; Malmo University Hospital, Malmo; AstraZeneca R&D, Molndal; and Umea University Hospital, Umea, Sweden) Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006. J Intern Med 2010; 268: 578-585. The risk of ischaemic heart disease (IHD), and in particular myocardial infarction (MI), is increased amongst patients with established rheumatoid arthritis (RA). Few studies have included contemporary patients with RA. We recently reported that the risk of IHD is not elevated before the onset of RA symptoms. However, when, in relation to RA diagnosis, the risk is increased is unknown. Objective. To assess the risk of MI and other IHD events amongst patients diagnosed with RA during the last decade and within 18 months following RA symptom onset, compared to the general population, by time since RA diagnosis, year of RA diagnosis and by rheumatoid factor (RF) status. Methods and patients. A Swedish inception cohort of RA (n = 7469) diagnosed between 1995 and 2006 and a matched general population comparator cohort (n = 37 024), was identified and linked to national registers of morbidity and mortality from IHD. Relative risks (RRs) of MI and other IHD events were estimated using Cox regression. Results. During follow-up, 233 patients with RA and 701 controls developed a first MI, corresponding to an overall RR of MI of 1.6 (95% confidence interval 1.4, 1.9). Increased risks of MI were already detected within 1-4 years following RA diagnosis, as well as in patients diagnosed with RA during the last 5 years, in RF-negative patients and for transmural as well as nontransmural MIs. Conclusions. MI risk increases rapidly following RA diagnosis, suggesting the importance of additional mechanisms other than atherosclerosis. The elevated short-term risk is present amongst patients diagnosed in recent years, underscoring the importance of MI prevention from the time of RA diagnosis.

  • 27.
    Hultdin, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Thøgersen, Ann Margreth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, T K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Elevated plasma homocysteine: cause or consequence of myocardial infarction?2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 256, no 6, p. 491-498Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine whether a first myocardial infarction leads to increased plasma homocysteine concentrations and whether the association between homocysteine and myocardial infarction was greater at follow-up compared with baseline. DESIGN: A population-based, prospective, nested case-referent study. SETTING: Screening took place at the nearest health survey centre in northern Sweden. SUBJECTS: Of more than 36,000 persons screened, 78 developed a first myocardial infarction (average 18 months after sampling). Fifty of these had participated in a follow-up health survey (average 8(1/2) years between surveys) and were sex- and age-matched with 56 referents. MAIN OUTCOME MEASURES: Comparison of plasma homocysteine levels in case and referent subjects before and after development of a first myocardial infarction. RESULTS: No statistically significant difference was found between cases and referents regarding homocysteine at baseline or follow-up. Plasma homocysteine and plasma creatinine increased significantly, and plasma albumin decreased significantly over time. Conditional univariate logistic regression indicated that high homocysteine at follow-up but not baseline was associated with first myocardial infarction (OR 2.49; 95% CI: 1.03-6.02), but the relation disappeared in multivariate analyses including plasma creatinine and plasma albumin. High plasma creatinine remained associated with first myocardial infarction at both baseline (OR 2.94; 95% CI: 1.05-8.21) and follow-up (OR 3.38; 95% CI: 1.21-9.48). CONCLUSION: In this study, first myocardial infarction did not cause increased plasma homocysteine concentration.

  • 28.
    Innala, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Andersson, Christer
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Reply to letter to the editor from prof Viroj Wiwanitkit, Bankok, Thailand2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 4, p. 397-397Article in journal (Refereed)
  • 29.
    Innala, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Andersson, Christer
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Screening for hepatocelular carcinoma in acute intermittent porphyria: A 15-year follow-up in northern Sweden2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 5, p. 538-545Article in journal (Other academic)
    Abstract [en]

    Objectives: To evaluate the benefit of screening for hepatocellular carcinoma (HCC) in gene carriers of acute intermittent porphyria (AIP) and estimate the annual incidence of HCC in this group.

    Subjects: All AIP gene carriers aged ≥55 years from the northernmost county in Sweden, Norrbotten, were invited for screening in this prospective study every 1–1.5 years during the period 1994–2009. We registered all HCC cases amongst AIP gene carriers in the northern region of Sweden (four counties). We compared gene carriers with repeated screening intervals of <2 years (Group A) with controls (Group B; i.e. gene carriers who had never been screened, those screened for the first time or screened at intervals of >2 years, or dropouts). The screening included radiological examination of the liver and relevant laboratory tests.

    Results, A total of 62 AIP subjects participated in the study, comprising 33% of the total AIP population aged >55 years in the northern region of Sweden. HCC was diagnosed in 22 AIP subjects (12 men and 10 women), mean age 69 (59–82) years. Amongst these subjects, 73% had experienced prior AIP attacks. The incidence rate ratio for HCC was 64 (52 in men and 93 in women). There were no cases of hepatitis B/C or alcohol abuse. Liver cirrhosis was rare. Liver resection could be performed in most subjects in Group A. Fourteen patients died of HCC, one in Group A and 13 in Group B. Compared with those who were not screened regularly, screening was associated with improved 3-year and 5-year survival (P = 0.005 and 0.038).

    Conclusions, Screening for HCC in carriers of AIP enables early diagnosis and a choice of potentially curative treatments with improved prognosis. We recommend annual screening using liver imaging for AIP gene carriers >50 years of age.

  • 30.
    Johansson, Elias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Delay from symptoms to carotid endarterectomy2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 263, no 4, p. 404-411Article in journal (Refereed)
    Abstract [en]

    Objectives.  To investigate the time between cerebrovascular symptom and carotid endarterectomy (CEA), what prolongs this time and if and when the patients suffer additional cerebrovascular events.

    Design.  Observational.

    Setting.  Single Centre study at a specialized Stroke Centre.

    Subjects.  A total of 275 patients with ≥50% symptomatic carotid stenosis (according to the NASCET-criteria) between 1 January 2004 and 31 March 2006.

    Main outcome measures.  Time between cerebrovascular symptom and CEA, time between different parts of the investigation, additional cerebrovascular symptoms before CEA and as perioperative complication.

    Results.  A total of 128 patients underwent CEA. The median time between symptom and CEA was 11.7 weeks in the beginning and 6.9 weeks at the end of the study. Seven per cent were operated within 2 weeks and 11% between 2 and 4 weeks after their cerebrovascular symptom. The time delays were most pronounced between symptom onset and arrival at the Umeå Stroke Centre from the secondary hospitals and between the decision to recommend CEA and the CEA. Twenty-eight per cent of the patients who were intended for surgery suffered additional cerebrovascular events, 1.4% suffered a major stroke which excluded the indication of CEA and 3.0% of the CEA patients suffered a stroke with functional dependence within 30 days of the operation.

    Conclusions.  The delay between symptom and CEA was substantially longer than the desired 2 weeks. Many patients suffered additional cerebrovascular events before CEA. The risk of a severe additional stroke before CEA was about the same as the risk of a severe complication from the CEA.

  • 31.
    Johansson, Elias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Öhman, K.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Symptomatic carotid near-occlusion with full collapse might cause a very high risk of stroke2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 5, p. 615-623Article in journal (Refereed)
    Abstract [en]

    BackgroundThe risk of early stroke recurrence amongst patients with symptomatic carotid near-occlusion with and without full collapse is unknown. Therefore, the aim of this study was to analyse the 90-day risk of recurrent ipsilateral ischaemic stroke in patients with symptomatic carotid near-occlusion both with and without full collapse. MethodsThis study was a secondary analysis of the Additional Neurological SYmptoms before Surgery of the Carotid Arteries: a Prospective study (ANSYSCAP). We prospectively analysed 230 consecutive patients with symptomatic 50-99% carotid stenosis or near-occlusion. Based on the combination of several imaging modalities, 205 (89%) patients were classified as having 50-99% carotid stenosis, and 10 (4%) and 15 (7%) as having near-occlusion with and without full collapse, respectively. The 90-day risk of recurrent ipsilateral ischaemic stroke was compared between these three groups. Only events that occurred before carotid endarterectomy were analysed. ResultsThe 90-day risk of recurrent stroke was 18% [95% confidence interval (CI) 12-25%; n=29] for patients with 50-99% carotid stenosis, 0% for patients with near-occlusion without full collapse and 43% (95% CI 25-89%; n=4) for patients with near-occlusion with full collapse (P=0.035, log-rank test). The increased risk of recurrent ipsilateral ischaemic stroke for patients with symptomatic near-occlusion with full collapse remained significant after multivariable adjustment for age, sex and type of presenting event. ConclusionsPatients with symptomatic carotid near-occlusion with full collapse might have a very high risk of stroke recurrence. Carotid endarterectomy could be considered for these patients.

  • 32. Katsoulis, M
    et al.
    Benetou, V
    Karapetyan, T
    Feskanich, D
    Grodstein, F
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Wilsgaard, T
    Jørgensen, L
    Ahmed, L A
    Schöttker, B
    Brenner, H
    Bellavia, A
    Wolk, A
    Kubinova, R
    Stegeman, B
    Bobak, M
    Boffetta, P
    Trichopoulou, A
    Excess mortality after hip fracture in elderly persons from Europe and the USA: the CHANCES project2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 3, p. 300-310Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hip fractures are associated with diminished quality of life and survival especially amongst the elderly.

    OBJECTIVE: All-cause mortality after hip fracture was investigated to assess its magnitude.

    METHODS: A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.6 years, accumulating 4273 incident hip fractures and 27 999 deaths. Incident hip fractures were assessed through telephone interviews/questionnaires or national inpatient/fracture registries, and causes of death were verified with death certificates. Cox proportional hazards models and the time-dependent variable methodology were used to assess the association between hip fracture and mortality and its magnitude at different time intervals after the injury in each cohort. We obtained the effect estimates through a random-effects meta-analysis.

    RESULTS: Hip fracture was positively associated with increased all-cause mortality; the hazard ratio (HR) in the fully adjusted model was 2.12, 95% confidence interval (CI) 1.76-2.57, after adjusting for potential confounders. This association was stronger amongst men [HR: 2.39, 95% CI: 1.72-3.31] than amongst women [HR: 1.92, 95% CI: 1.54-2.39], although this difference was not significant. Mortality was higher during the first year after the hip fracture [HR: 2.78, 95% CI: 2.12-3.64], but it remained elevated without major fluctuations after longer time since hip fracture [HR (95% CI): 1.89 (1.50-2.37) after 1-4 years; 2.15 (1.81-2.55) after 4-8 years; 1.79 (1.57-2.05) after 8 or more years].

    CONCLUSION: In this large population-based sample of older persons across eight cohorts, hip fracture was associated with excess short- and long-term all-cause mortality in both sexes.

  • 33. Klingstrom, J.
    et al.
    Smed-Sörensen, A.
    Maleki, K. T.
    Sola-Riera, C.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Björkström, N. K.
    Ljunggren, H. G.
    Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus-associated syndromes2019In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 285, no 5, p. 510-523Article in journal (Refereed)
    Abstract [en]

    Two related hyperinflammatory syndromes are distinguished following infection of humans with hantaviruses: haemorrhagic fever with renal syndrome (HFRS) seen in Eurasia and hantavirus pulmonary syndrome (HPS) seen in the Americas. Fatality rates are high, up to 10% for HFRS and around 35%-40% for HPS. Puumala virus (PUUV) is the most common HFRS-causing hantavirus in Europe. Here, we describe recent insights into the generation of innate and adaptive cell-mediated immune responses following clinical infection with PUUV. First described are studies demonstrating a marked redistribution of peripheral blood mononuclear phagocytes (MNP) to the airways, a process that may underlie local immune activation at the site of primary infection. We then describe observations of an excessive natural killer (NK) cell activation and the persistence of highly elevated numbers of NK cells in peripheral blood following PUUV infection. A similar vigorous CD8 Tcell response is also described, though Tcell responses decline with viraemia. Like MNPs, many NK cells and CD8 T cells also localize to the lung upon acute PUUV infection. Following this, findings demonstrating the ability of hantaviruses, including PUUV, to cause apoptosis resistance in infected target cells, are described. These observations, and associated inflammatory cytokine responses, may provide new insights into HFRS and HPS disease pathogenesis. Based on similarities between inflammatory responses in severe hantavirus infections and other hyperinflammatory disease syndromes, we speculate whether some therapeutic interventions that have been successful in the latter conditions may also be applicable in severe hantavirus infections.

  • 34. Langrish, J. P.
    et al.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Muala, Ala
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, D. E.
    Mills, N. L.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Cardiovascular effects of particulate air pollution exposure: time course and underlying mechanisms2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 272, no 3, p. 224-239Article, review/survey (Refereed)
    Abstract [en]

    Objective Air pollution is now recognized as an important independent risk factor for cardiovascular morbidity and mortality and may be responsible for up to 3 similar to million premature deaths each year worldwide. The mechanisms underlying the observed effects are poorly understood but are likely to be multifactorial. Here, we review the acute and chronic effects of air pollution exposure on the cardiovascular system and discuss how these effects may explain the observed increases in cardiovascular morbidity and mortality.

  • 35.
    Lerner, Ulf H
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Centre for Bone and Arthritis Research, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Ohlsson, C
    Centre for Bone and Arthritis Research, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    The WNT system: background and its role in bone2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 6, p. 630-649Article in journal (Refereed)
    Abstract [en]

    WNTs are extracellular proteins that activate different cell surface receptors linked to canonical and noncanonical WNT signalling pathways. The Wnt genes were originally discovered as important for embryonic development of fruit flies and malignant transformation of mouse mammary cancers. More recently, WNTs have been implicated in a wide spectrum of biological phenomena and diseases. During the last decade, several lines of clinical and preclinical evidence have indicated that WNT signalling is critical for trabecular and cortical bone mass, and this pathway is currently an attractive target for drug development. Based on detailed knowledge of the different WNT signalling pathways, it appears that it might be possible to develop drugs that specifically target cortical and trabecular bone. Neutralization of a bone-specific WNT inhibitor is now being evaluated as a promising anabolic treatment for patients with osteoporosis. Here, we provide the historical background to the discoveries of WNTs, describe the different WNT signalling pathways and summarize the current understanding of how these proteins regulate bone mass by affecting bone formation and resorption.

  • 36. Lewerin, C.
    et al.
    Johansson, H.
    Karlsson, M. K.
    Lorentzon, M.
    Lerner, Ulf H.
    Umeå University, Faculty of Medicine, Department of Odontology. Univ Gothenburg, CBAR, Dept Internal Med, Sahlgrenska Acad,Inst Med, Gothenburg, Sweden.
    Kindblom, J. M.
    Ohlsson, C.
    Smith, U.
    Mellstrom, D.
    High plasma osteocalcin is associated with low blood haemoglobin in elderly men: the MrOS Sweden Study2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 280, no 4, p. 398-406Article in journal (Refereed)
    Abstract [en]

    Background. It has been suggested that osteoblasts are involved in the regulation of haematopoietic stem cells. Whether osteocalcin, which is derived from osteoblasts and is metabolically active, influences blood haemoglobin (Hb) levels is not known. Objective. To determine whether plasma osteocalcin is a determinant of Hb in elderly men. Methods. A total of 993 men (mean age 75.3 +/- 3.2 years) participated in the population-based MrOS (osteoporotic fractures in men) study. Plasma osteocalcin concentration was evaluated in relation to Hb and adjustments were made for potential confounders (i.e. age, body mass index, erythropoietin, total oestradiol, fasting insulin, adiponectin, ferritin and cystatin C). Results. Hb correlated (age adjusted) negatively with osteocalcin in the total study group (r = -0.12, P < 0.001) as well as in the subgroup of nondiabetic men(r = -0.16, P < 0.001). In nondiabetic menwith higher osteocalcin levels, it was more likely that Hb would be in the lowest quartile (odds ratio per SD decrease in osteocalcin 1.32, 95% confidence interval 1.13-1.53). Quartiles of Hb were negatively associated (age adjusted) with osteocalcin (P < 0.001). Anaemic men (47/812) (Hb < 130 mu g L-1) had significantly higher mean osteocalcin levels than nonanaemic men (33.9 vs. 27.1 mu g L-1, P < 0.001). In multiple stepwise linear regression analyses (adjusted for age, body mass index, total oestradiol, adiponectin, erythropoietin, fasting insulin, cystatin C, leptin, ferritin and holotranscobalamin), osteocalcin was an independent predictor of Hb concentration in nondiabetic men (P < 0.05). Conclusions. These data add further support to the evidence indicating that the bone-specific protein osteocalcin has several endocrine functions targeting the pancreas, testes, adipocytes, brain. An additional novel finding is that osteocalcin may also have a paracrine function as a regulator of haematopoiesis.

  • 37. Lewerin, C.
    et al.
    Johansson, H.
    Lerner, Ulf H.
    Umeå University, Faculty of Medicine, Department of Odontology. Center for Bone and Arthritis Research (CBAR) and Geriatric Medicine, Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Karlsson, M. K.
    Lorentzon, M.
    Barrett-Connor, E.
    Smith, U.
    Ohlsson, C.
    Mellstrom, D.
    High serum adiponectin is associated with low blood haemoglobin in elderly men: the Swedish MrOS study2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, no 1, p. 68-76Article in journal (Refereed)
    Abstract [en]

    Objectives: Blood haemoglobin (Hb) concentration declines in elderly men, whilst the level of the adipocyte-derived protein adiponectin increases with age. The association between erythropoiesis and adiponectin in elderly men is unclear. The aim of this study was to determine whether adipokines such as adiponectin and leptin are associated with anaemia and Hb concentration in elderly community-dwelling men.

    Design and setting: The Gothenburg part of the population-based Swedish Osteoporotic Fractures in Men (MrOS) cohort (n=1010; median age 75.3years, range 69-81).

    Main outcome measures: We investigated the associations between levels of adiponectin and Hb before and after adjusting for potential confounders [i.e. age, body composition, erythropoietin (EPO), total oestradiol, leptin, cystatin C and iron and B vitamin status].

    Results: In these elderly men, age was negatively associated with Hb (r=-0.12, P<0.001) and positively associated with adiponectin level (r=0.13, P<0.001). In age-adjusted partial correlations, Hb and adiponectin levels were negatively correlated (r=-0.20, P<0.001); this association remained significant after multivariable adjustment for age, body composition, EPO, fasting insulin, sex hormones, leptin and ferritin. Age-adjusted mean adiponectin concentrations were significantly higher in anaemic men (66/1005; Hb <130gL(-1)) compared to nonanaemic men (14.0 vs. 11.7 gmL(-1), P<0.05). In multivariate analysis, adiponectin together with EPO, total oestradiol, insulin, albumin, transferrin saturation, HDL cholesterol, cystatin C, total body fat mass and free thyroxine, but not leptin, explained 35% of the variation in Hb level. These results remained essentially unchanged after exclusion of men with diabetes.

    Conclusions: Serum adiponectin, but not leptin, was negatively and independently associated with Hb. This finding suggests a possible role of adiponectin in the age-related decline in Hb level observed in apparently healthy elderly men.

  • 38.
    Lind, Marcus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Slunga-Järvholm, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Von Willebrand factor predicts major bleeding and mortality during oral anticoagulant treatment2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 271, no 3, p. 239-246Article in journal (Refereed)
    Abstract [en]

    Aims.  Oral anticoagulation (OAC), predominantly with warfarin, is an effective treatment to prevent thromboembolic events. Serious bleeding is a frequent and feared treatment complication. In this longitudinal cohort study of OAC-treated patients, we aimed to evaluate the relationship between von Willebrand factor (VWF) levels and risk of bleeding complications, cardiovascular mortality and all-cause mortality.

    Methods and results.  A total of 719 patients receiving warfarin treatment were observed for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified into clinically relevant bleeding (CRB) and major bleeding. Ischaemic stroke, peripheral arterial embolism, myocardial infarction, and death were also recorded. We identified 113 cases of CRB and 73 of major bleeding. In total, 161 deaths occurred during follow-up with cardiovascular disease identified as the cause of death in 110 patients. Patients in the highest tertile of VWF had a significantly increased risk of bleeding complications: hazard ratio (HR) 2.53 (95% CI 1.41-4.56) for major bleeding and HR 2.19 (95% CI 1.38-3.48) for CRB. VWF, expressed either in tertiles or as a continuous variable, showed a significant association with cardiovascular mortality (HR 1.68, 95% CI 1.40-2.01) and all-cause mortality (HR 1.77, 95% CI 1.52-2.05). In multivariate Cox regression analysis, the findings remained significant after adjusting for age, high-sensitivity C-reactive protein and creatinine.

    Conclusions.  Patients with high levels of VWF had an increased risk of bleeding complications, cardiovascular mortality and all-cause mortality during OAC treatment. Our findings imply that the use of VWF as a risk marker for thromboembolic events is complicated by the association of VWF with bleeding complications.

  • 39. Lindeberg, S
    et al.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ahrén, B
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Large differences in serum leptin levels between nonwesternized and westernized populations: the Kitava study.2001In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 249, no 6, p. 553-558Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To compare serum leptin between nonwesternized and westernized populations.

    SETTING: (i) The tropical island of Kitava, Trobriand Islands, Papua New Guinea and (ii) the Northern Sweden MONICA study population. Design. Cross-sectional survey.

    METHODS: Fasting levels of serum leptin were analysed in 163 randomly selected Kitavans aged 20-86 years and in 224 Swedes aged 25-74.

    MAIN OUTCOME MEASURE: Mean and determinants of serum leptin.

    RESULTS: Geometric mean of serum leptin in Kitavan males and females were 1.5 and 4.0 vs. 4.9 and 13.8 ng mL-1 in Swedish male and females (P < 0.0001 for both sexes). In Kitavans, observed geometric mean were close to predicted levels (1.8 ng mL(-1) for males and 4.5 ng mL-1 for females) based on multiple linear regression equations including body mass index (BMI), triceps skinfolds (TSF) and age from the Swedish population-based sample. In Kitavans serum leptin was positively related to TSF amongst both sexes and, amongst females, to BMI. In Kitavans leptin was not related to fasting serum insulin. TSF explained 55% of the variation of leptin amongst females. There was a slight age-related increase of leptin amongst males. In Kitava leptin was not related to fasting serum insulin which was substantially lower than in Sweden.

    CONCLUSION: The low concentrations of serum leptin amongst Kitavans probably relates to the absence of overweight and hyperinsulinaemia. At a population level serum leptin can apparently be predicted from simple measures of adiposity.

  • 40.
    Lundblad, Dan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Internal Medicine, Sunderby Hospital, Luleå.
    Dinesen, B
    Rautio, Aslak
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Internal Medicine, Sunderby Hospital, Luleå.
    Roder, M E
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Internal Medicine, Sunderby Hospital, Luleå.
    Low level of tissue plasminogen activator activity innon-diabetic patients with a first myocardial infarction2005In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 258, no 1, p. 13-20Article in journal (Refereed)
    Abstract [en]

    Objective. To explore the role of tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor type 1 (PAI-1) in survivors of a first myocardial infarction (MI). Insulin and proinsulin were analysed as potential risk factors. Design. Case-control study in northern Sweden. Subjects. A total of 115 patients under 65 years of age with a first MI were enrolled and recalled for further examination 3 months later. Twenty-seven patients were excluded, 17 with known diabetes and 10 who did not come to the follow-up, giving a final number of 88 patients, 73 men and 15 women. Patients were age- and sex matched with control subjects drawn from the local cohort in the MONICA population survey 1994. Main outcome measures. We compared MI patients and controls using univariate and multiple regression analyses including odds ratios (OR). Results. PAI-1 activity, fibrinogen, postload insulin and -proinsulin were significantly higher and tPA activity significantly lower in MI patients in the univariate analysis. In a multiple regression analysis, including also age, sex and cardiovascular risk factors, these parameters were divided in quartiles. The lowest quartile of tPA activity was significantly associated with MI (OR = 19.1; CI 3.0-123) together with the highest quartiles of fibrinogen (OR = 25; CI 5.2-120) but other variables were not. Conclusion. Low tPA activity, i.e. low fibrinolytic activity, characterized nondiabetic subjects after a first MI which is not explained by concomitant disturbances in metabolic and anthropometric variables

  • 41. Mofors, J.
    et al.
    Arkema, E. V.
    Björk, A.
    Westermark, L.
    Kvarnström, M.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Magnusson Bucher, S.
    Eriksson, P.
    Mandl, T.
    Nordmark, G.
    Wahren-Herlenius, M.
    Infections increase the risk of developing Sjögren's syndrome2019In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 285, no 6, p. 670-680Article in journal (Refereed)
    Abstract [en]

    Objective: Environmental factors have been suggested in the pathogenesis of rheumatic diseases. We here investigated whether infections increase the risk of developing primary Sjögren's syndrome (pSS).

    Methods: Patients with pSS in Sweden (n = 945) and matched controls from the general population (n = 9048) were included, and data extracted from the National Patient Register to identify infections occurring before pSS diagnosis during a mean observational time of 16.0 years. Data were analysed using conditional logistic regression models. Sensitivity analyses were performed by varying exposure definition and adjusting for previous health care consumption.

    Results: A history of infection associated with an increased risk of pSS (OR 1.9, 95% CI 1.6–2.3). Infections were more prominently associated with the development of SSA/SSB autoantibody‐positive pSS (OR 2.7, 95% CI 2.0–3.5). When stratifying the analysis by organ system infected, respiratory infections increased the risk of developing pSS, both in patients with (OR 2.9, 95% CI 1.8–4.7) and without autoantibodies (OR 2.1, 95% CI 1.1–3.8), whilst skin and urogenital infections only significantly associated with the development of autoantibody‐positive pSS (OR 3.2, 95% CI 1.8–5.5 and OR 2.7, 95% CI 1.7–4.2). Furthermore, a dose–response relationship was observed for infections and a risk to develop pSS with Ro/SSA and La/SSB antibodies. Gastrointestinal infections were not significantly associated with a risk of pSS.

    Conclusions: Infections increase the risk of developing pSS, most prominently SSA/SSB autoantibody‐positive disease, suggesting that microbial triggers of immunity may partake in the pathogenetic process of pSS.

  • 42. Mofors, J.
    et al.
    Holmqvist, M.
    Westermark, L.
    Björk, A.
    Kvarnström, M.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Bucher, S. Magnusson
    Eriksson, P.
    Theander, E.
    Mandl, T.
    Wahren-Herlenius, M.
    Nordmark, G.
    Concomitant Ro/SSA and La/SSB antibodies are biomarkers for the risk of venous thromboembolism and cerebral infarction in primary Sjögren's syndrome2019In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 4, p. 458-468Article in journal (Refereed)
    Abstract [en]

    Background: To assess the risk of incident cardiovascular disease in patients with primary Sjögren's syndrome, overall and stratified by Ro/SSA and La/SSB autoantibody status.

    Methods: A cohort of patients with primary Sjögren's syndrome in Sweden (n = 960) and matched controls from the general population (n = 9035) were included, and data extracted from the National Patient Register to identify events of myocardial infarction, cerebral infarction and venous thromboembolism. Hazard ratios were estimated using cox proportional hazard regressions.

    Results: During a median follow‐up of 9.5 years, the overall hazard ratio (HR) was 1.6 (95% CI 1.2–2.1) for myocardial infarction, 1.2 (95% CI 0.9–1.7) for cerebral infarction and 2.1 (95% CI 1.6–2.9) for venous thromboembolism. Patients positive for both Ro/SSA and La/SSB autoantibodies had a substantially higher risk of cerebral infarction (HR 1.7, 95% CI 1.0–2.9) and venous thromboembolism (HR 3.1, 95% CI 1.9–4.8) than the general population. These risks were not significantly increased in Ro/SSA‐ and La/SSB‐negative patients. Among autoantibody‐positive patients, the highest HR of cerebral infarction was seen after ≥10 years disease duration (HR 2.8, 95% CI 1.4–5.4), while the HR for venous thromboembolism was highest 0–5 years after disease diagnosis (HR 4.7, 95% CI 2.3–9.3) and remained high throughout disease duration.

    Conclusions: Primary Sjögren's syndrome is associated with a markedly increased risk of cardiovascular disease and the presence of Ro/SSA and La/SSB autoantibodies identify the subgroup of patients carrying the highest risk. These findings suggest that monitoring and prevention of cardiovascular disease in this patient group should be considered.

  • 43.
    Murray, V
    et al.
    Department of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden.
    Norrving, B
    Department of Neurology, University Hospital, Lund, Sweden.
    Sandercock, P A G
    Division of Clinical Neurosciences, Western General Hospital, University of Edinburgh, Edinburgh, UK.
    Terént, A
    Department of Medical Sciences, Acute and Internal Medicine, Academic Hospital, Uppsala, Sweden.
    Wardlaw, J M
    Division of Clinical Neurosciences, Western General Hospital, University of Edinburgh, Edinburgh, UK.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The molecular basis of thrombolysis and its clinical application in stroke2010In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 267, no 2, p. 191-208Article in journal (Refereed)
    Abstract [en]

    The rationale for thrombolysis, the most promising pharmacological approach in acute ischaemic stroke, is centred on the principal cause of most ischaemic strokes: the thrombus that occludes the cerebral artery, and renders part of the brain ischaemic. The occluding thrombus is bound together within fibrin. Fibrinolysis acts by activation of plasminogen to plasmin; plasmin splits fibrinogen and fibrin and lyses the clot, which then allows reperfusion of the ischaemic brain. Thrombolytic agents include streptokinase (SK) and recombinant tissue-type plasminogen activator (rt-PA) amongst others under test or development. SK is nonfibrin-specific, has a longer half-life than tissue-type plasminogen activator (t-PA), prevents re-occlusion and is degraded enzymatically in the circulation. rt-PA is more fibrin-specific and clot-dissolving, and is metabolized during the first passage in the liver. In animal models of ischaemic stroke, the effects of rt-PA are remarkably consistent with the effects seen in human clinical trials. For clinical application, some outcome data from the Cochrane Database of Systematic Reviews which includes all randomized evidence available on thrombolysis in man were used. Trials included tested urokinase, SK, rt-PA, pro-urokinase, or desmoteplase. The chief immediate hazard of thrombolytic therapy is fatal intracranial bleeding. However, despite the risk, the human trial data suggest the immediate hazards and the apparent substantial scope for net benefit of thrombolytic therapy given up to 6 h of acute ischaemic stroke. So far the fibrin-specific rt-PA is the only agent to be approved for use in stroke. This may be due to its short half-life and its absence of any specific amount of circulating fibrinogen degradation products, thereby leaving platelet function intact. The short half-life does not leave rt-PA without danger for haemorrhage after the infusion. Due to its fibrin-specificity, it can persist within a fibrin-rich clot for one or more days. The molecular mechanisms with regards to fibrin-specificity in thrombolytic agents should, if further studied, be addressed in within-trial comparisons. rt-PA has antigenic properties and although their long-term clinical relevance is unclear there should be surveillance for allergic reactions in relation to treatment. Although rt-PA is approved for use in selected patients, there is scope for benefit in a much wider variety of patients. A number of trials are underway to assess which additional patients - beyond the age and time limits of the current approval - might benefit, and how best to identify them.

  • 44.
    Mörner, Stellan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Kazzam, Elsadig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Amyloid heart disease mimicking hypertrophic cardiomyopathy.2005In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 258, no 3, p. 225-230Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the importance of transthyretin (TTR) gene mutations in explaining the phenotypic expression in patients diagnosed with hypertrophic cardiomyopathy (HCM) in northern Sweden. BACKGROUND: Hypertrophic cardiomyopathy is relatively common and often caused by mutations in sarcomeric protein genes. Mutations in the TTR gene are also common, one of which causes familial amyloid polyneuropathy (FAP), with peripheral polyneuropathy and frequently, cardiac hypertrophy. These circumstances were highlighted by the finding of an index case with amyloidosis, presenting itself as HCM. Initial rectal and fat biopsies did not show amyloid deposits. Later on, the patient was shown to carry a TTR gene mutation, and cardiac amyloidosis was confirmed by myocardial biopsy. Only then was a repeated fat biopsy positive for amyloid deposits. DESIGN: Cross-sectional study. SETTING: Cardiology tertiary referral centre. SUBJECTS: Forty-six unrelated individuals with HCM and the index case were included. Common diagnostic criteria for HCM were used. The 46 patients with HCM were previously analysed for mutations in eight sarcomeric protein genes and the TTR gene was now analysed by denaturing high-performance liquid chromatography and direct sequencing. RESULTS: One mutation in the TTR gene (Val30Met) was found in three individuals and the index case. CONCLUSIONS: Three of the 46 cases with HCM carried the Val30Met mutation, and were considered likely to have cardiac amyloidosis, like the index case. As a correct diagnosis of cardiac amyloidosis is mandatory for a potentially life-saving treatment, TTR mutation analysis should be considered in cases of HCM not explained by mutations in sarcomeric protein genes.

  • 45.
    Mörner, Stellan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mellberg, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olofsson, Bert-Ove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Backman, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Forsberg, H
    Profound cardiac conduction delay predicts mortality in myotonic dystrophy type 1.2010In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 268, no 1, p. 59-65Article in journal (Refereed)
    Abstract [en]

    Background. Myotonic dystrophy type 1 (DM1) is known to affect mainly the musculoskeletal system. Early mortality is related to respiratory disease and possibly additional cardiovascular complications. Aims. To identify possible cardiovascular disturbances that could predict survival of DM1 patients. Methods. We studied 30 DM1 patients (mean age 41 +/- 13.5 years, range 16-71, 15 women) who were cardiovascularly stable and compared them with 29 controls (mean age 55 +/- 7.8 years, range 42-66, 14 women) using electrocardiography (ECG) and conventional transthoracic echocardiography. The subgroup that survived a follow-up period of 17 years was re-examined using the same protocol. Results. Of the 30 patients, 10 died of a documented respiratory cause and three of acute myocardial incidents. Compared with controls, left ventricular cavity size, corrected to body surface area, was slightly enlarged at end systole (P < 0.05) and hence fractional shortening was reduced (P < 0.01). Nine patients had first-degree heart block and 15 had a QRS duration >90 ms. Of all ECG and echocardiographic measurements, the sum of QRS duration + PR interval was the best predictor of mortality as shown by the area under the receiver operating characteristic curve of 85%, sensitivity of 70% and specificity of 84%. Conclusions. These findings suggest that silent cardiac dysfunction in DM1 patients may cause significant disturbances that over time result in serious complications. Regular follow-up of such patients with detailed electrical and mechanical cardiac assessment may suggest a need for early intervention that may avoid early mortality in some.

  • 46.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Air pollution and its cardiovascular and other risks2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 271, no 5, p. 429-432Article in journal (Refereed)
  • 47.
    Nilsson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The Effect of Streptokinase Neutralising Antibodies on Fibrinolytic Activity and Reperfusion Following Streptokinase Treatment in Acute Myocardial Infarction.2002In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 252, no 5, p. 405-411Article in journal (Refereed)
  • 48.
    Nilsson, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Trehn, G
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Use of complementary and alternative medicine remedies in Sweden. A population-based longitudinal study within the northern Sweden MONICA Project. Multinational Monitoring of Trends and Determinants of Cardiovascular Disease.2001In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 250, no 3, p. 225-33Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Previous studies have shown a high prevalence of users of complementary and alternative medicine (CAM) remedies in Anglo-Saxon countries. We have explored the use of CAM remedies in Sweden, its distribution in different population groups and time trends during the years 1990-99. DESIGN AND SUBJECTS: Within the framework of the population-based northern Sweden Multinational Monitoring of Trends and Determinants of Cardiovascular Disease (MONICA) Project, randomly selected 25-74-year-old participants in risk factor surveys performed in 1990, 1994 and 1999 responded to questions about their use of CAM remedies. The participation rate was 72%. RESULTS: Amongst 5794 respondents in the 1999 survey, 30.5% reported that they had taken a CAM product (vitamins, minerals or biological CAM remedy) in the preceding 2 weeks. Vitamins/minerals only had been taken by 11.7% and other CAM remedies (dominated by fish oil, ginseng and Q10) with or without vitamins/minerals by 18.8%. Use of CAM remedies was more frequent in women than in men and more frequent in people with high than with low level of education. The prevalence was unrelated to a history of severe cardiovascular disease or diabetes but significantly more common in subjects with poor self-perceived health, particularly so in women. During 1990-99, the use of CAM remedies increased, more in women than in men. CONCLUSIONS: The prevalence of CAM remedy use (other than vitamins and minerals) is high in Sweden. It has been increasing during the 1990s. Its use is particularly common in women, well-educated people and in those with poor self-perceived health.

  • 49.
    Norberg, Margareta
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindahl, B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Andersson, Christer
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    A combination of HbA1c, fasting glucose and BMI is effective in screening for individuals at risk of future type 2 diabetes: OGTT is not needed.2006In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 260, no 3, p. 263-71Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To identify a screening model that predicts high risk of future type 2 diabetes and is useful in clinical practice. DESIGN AND METHODS: Incident case-referent study nested within a population-based health survey. We compared screening models with three risk criteria and calculated sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and attributable proportion. We used fasting plasma glucose (FPG) alone or with an oral glucose tolerance test (OGTT), glycosylated haemoglobin A (HbA1c) (normal range 3.6-5.3%), body mass index (BMI), triglycerides and family history of diabetes (FHD). SETTING: Participants in a health survey at all primary care centres (n=33,336) and subjects with diagnosed type 2 diabetes in primary and hospital care (n=6088) in Umeå during 1989-2001. SUBJECTS: Each of the 164 subjects who developed clinically diagnosed type 2 diabetes (median time to diagnosis of 5.4 years) and 304 sex- and age-matched referents without diabetes diagnosis. RESULTS: Screening models with at least one criterion present had sensitivities of 0.90-0.96, specificities of 0.43-0.57 and PPVs of 8-9%. Combinations of the criteria, FPG>or=6.1 mmol L-1 (capillary plasma), HbA1c>or=4.7% and BMI>or=27 in men and BMI>or=30 in women, had sensitivities, specificities and PPVs of 0.66%, 0.93% and 32%, and 0.52%, 0.97% and 46% respectively. Using FHD as one of three risk criteria showed comparable results. Addition of triglycerides or OGTT did not improve the prediction. CONCLUSIONS: The combination of HbA1c, FPG and BMI are effective in screening for individuals at risk of future clinical diagnosis of type 2 diabetes. OGTT or FHD is not necessary.

  • 50.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Functional brain imaging of episodic memory decline in ageing2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 1, p. 65-74Article, review/survey (Refereed)
    Abstract [en]

    The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus–neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation.

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