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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. Atterman, A.
    et al.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Friberg, L.
    Engdahl, J.
    Use of oral anticoagulants after ischaemic stroke in patients with atrial fibrillation and cancer2020In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 288, no 4, p. 457-468Article in journal (Refereed)
    Abstract [en]

    Background and objectives: The use of oral anticoagulants (OACs) amongst patients with atrial fibrillation (AF) has increased in the last decade. We aimed to describe temporal trends in the utilization of OACs for secondary prevention after ischaemic stroke amongst patients with AF and active cancer.

    Methods: This is a cross-sectional and cohort study of patients with active cancer (n = 1518) and without cancer (n = 50 953) in the Swedish national register Riksstroke, including all patients with ischaemic stroke between 1 July 2005 and 30 December 2017, discharged with AF. Prescription and dispensation before and after the introduction of nonvitamin K OACs (NOACs) in late 2011 were compared. We used logistic and Cox regression to analyse associations with OAC use, adjusting for hospital clustering and the competing risk of death.

    Results: The proportion of cancer patients with AF prescribed OACs at discharge after ischaemic stroke increased by 40.2% after 2011, compared with 69.3% in noncancer patients during the same period. Stroke and bleeding risk scores remained similar between patients with and without cancer. OAC dispensation during the following year did not increase as much in cancer patients (43.8% to 64.5%) as that in noncancer patients (46.0% to 74.9%), and the median time to OAC dispensation or censoring was significantly longer in cancer patients (94 vs. 30 days).

    Conclusion: OAC treatment in poststroke patients with AF and active cancer has increased after the introduction of NOACs. However, the growing treatment gap in these patients compared to that in noncancer patients raises the possibility of underutilization.

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  • 11.
    Ballin, Marcel
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Does exercise prevent major non-communicable diseases and premature mortality?: A critical review based on results from randomized controlled trials2021In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 290, no 6, p. 1112-1129Article, review/survey (Refereed)
    Abstract [en]

    Observational studies show that physical activity is strongly associated with a reduced risk of premature mortality and major non-communicable diseases. We reviewed to which extent these associations have been confirmed in randomized controlled trials (RCTs) for the outcomes of mortality, cardiovascular disease (CVD), type 2 diabetes (T2D), and fracture. The results show that exercise does not reduce all-cause mortality and incident CVD in older adults or in people with chronic conditions, based on RCTs comprising ∼50,000 participants. The results also indicate a lack of effect on cardiovascular mortality in people with chronic conditions, based on RCTs comprising ∼11,000 participants. Furthermore, there is inconsistent evidence regarding the effect of exercise on fractures in older adults, based on RCTs comprising ∼40,000 participants. Finally, based on RCTs comprising ∼17,000 participants, exercise reduces T2D incidence in people with prediabetes when combined with dietary modification, although evidence for the individual effect of exercise is lacking. Identified shortcomings of the current evidence include risks of publication bias, lack of high-quality studies in certain high-risk populations, and inconstant evidence with respect to some outcomes. Thus, additional large trials would be of value, especially with fracture as the primary outcome. In conclusion, according to current RCT evidence, exercise can prevent T2D assuming it is combined with dietary intervention. However, the current evidence shows that exercise does not prevent premature mortality or CVD, with inconsistent evidence for fractures.

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  • 12. 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.

  • 13. 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.

  • 14.
    Bergthorsdottir, Ragnhildur
    et al.
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Esposito, Daniela
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Olsson, Daniel S.
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden; Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Ragnarsson, Oskar
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden; Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bensing, Sophie
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital Stockholm, Sollentuna, Sweden.
    Nåtman, Jonatan
    Centre of Registers Västra Götaland, Gothenburg, Sweden.
    Johannsson, Gudmundur
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nyberg, Fredrik
    School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Increased risk of hospitalization, intensive care and death due to covid-19 in patients with adrenal insufficiency: a Swedish nationwide study2024In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 295, no 3, p. 322-330Article in journal (Refereed)
    Abstract [en]

    Background: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown.

    Methods: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis.

    Results: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59–2.43), intensive care admission (2.76, 1.49–5.09) and death (2.29, 1.60–3.28).

    Conclusion: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.

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  • 15. 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.

  • 16. 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.

  • 17.
    Björsell, Tove
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Infectious Diseases, Karlstad Hospital, Karlstad, Sweden; Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden.
    Sundh, Josefin
    Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lange, Anna
    Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Tevell, Staffan
    Department of Infectious Diseases, Karlstad Hospital, Karlstad, Sweden; Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden; Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Edin, Alicia
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Cajander, Sara
    Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Risk factors for impaired respiratory function post COVID-19: a prospective cohort study of nonhospitalized and hospitalized patients2023In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 293, no 5, p. 600-614Article in journal (Refereed)
    Abstract [en]

    Background: Severe COVID-19 increases the risk for long-term respiratory impairment, but data after mild COVID-19 are scarce. Our aims were to determine risk factors for reduced respiratory function 3–6 months after COVID-19 infection and to investigate if reduced respiratory function would relate to impairment of exercise performance and breathlessness. Methods: Patients with COVID-19 were enrolled at the University Hospitals of Umeå and Örebro, and Karlstad Central Hospital, Sweden. Disease severity was defined as mild (nonhospitalized), moderate (hospitalized with or without oxygen treatment), and severe (intensive care). Spirometry, including diffusion capacity (DLCO), was performed 3–6 months after hospital discharge or study enrollment (for nonhospitalized patients). Breathlessness (defined as ≥1 according to the modified Medical Research Council scale) and functional exercise capacity (1-min sit-to-stand test; 1-MSTST) were assessed. Results: Between April 2020 and May 2021, 337 patients were enrolled in the study. Forced vital capacity and DLCO were significantly lower in patients with severe COVID-19. Among hospitalized patients, 20% had reduced DLCO, versus 4% in nonhospitalized. Breathlessness was found in 40.6% of the participants and was associated with impaired DLCO. A pathological desaturation or heart rate response was observed in 17% of participants during the 1-MSTST. However, this response was not associated with reduced DLCO. Conclusion: Reduced DLCO was the major respiratory impairment 3–6 months following COVID-19, with hospitalization as the most important risk factor. The lack of association between impaired DLCO and pathological physiological responses to exertion suggests that these physiological responses are not primarily related to decreased lung function.

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  • 18.
    Bäckström, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Turkmen, Sahruh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Das, Roshni
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umecrine Cognition AB, Solna, Sweden.
    Doverskog, Magnus
    Umecrine Cognition AB, Solna, Sweden.
    Blackburn, Thomas P.
    Umecrine Cognition AB, Solna, Sweden.
    The GABA system, a new target for medications against cognitive impairment—Associated with neuroactive steroids2023In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 294, no 3, p. 281-294Article, review/survey (Refereed)
    Abstract [en]

    The prevalence of cognitive dysfunction, dementia, and neurodegenerative disorders such as Alzheimer's disease (AD) is increasing in parallel with an aging population. Distinct types of chronic stress are thought to be instrumental in the development of cognitive impairment in central nervous system (CNS) disorders where cognitive impairment is a major unmet medical need. Increased GABAergic tone is a mediator of stress effects but is also a result of other factors in CNS disorders. Positive GABA-A receptor modulating stress and sex steroids (steroid-PAMs) such as allopregnanolone (ALLO) and medroxyprogesterone acetate can provoke impaired cognition. As such, ALLO impairs memory and learning in both animals and humans. In transgenic AD animal studies, continuous exposure to ALLO at physiological levels impairs cognition and increases degenerative AD pathology, whereas intermittent ALLO injections enhance cognition, indicating pleiotropic functions of ALLO. We have shown that GABA-A receptor modulating steroid antagonists (GAMSAs) can block the acute negative cognitive impairment of ALLO on memory in animal studies and in patients with cognitive impairment due to hepatic encephalopathy. Here we describe disorders affected by steroid-PAMs and opportunities to treat these adverse effects of steroid-PAMs with novel GAMSAs.

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  • 19.
    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)
  • 20. 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.

  • 21.
    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)
  • 22. 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.

  • 23. 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.

  • 24. Eimer, J.
    et al.
    Vesterbacka, J.
    Svensson, A.-K.
    Stojanovic, B.
    Wagrell, C.
    Sönnerborg, A.
    Nowak, P.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Unit of Infectious Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden; Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institute, Huddinge, Sweden.
    Tocilizumab shortens time on mechanical ventilation and length of hospital stay in patients with severe COVID-19: a retrospective cohort study2021In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 289, no 3, p. 434-436Article in journal (Refereed)
  • 25. Eldhagen, P.
    et al.
    Berg, S.
    Lund, L. H.
    Sörensson, P.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Westermark, P.
    Transthyretin amyloid deposits in lumbar spinal stenosis and assessment of signs of systemic amyloidosis2021In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 289, no 6, p. 895-905Article in journal (Refereed)
    Abstract [en]

    Background: Wild‐type transthyretin (ATTRwt) amyloidosis is the most common systemic amyloidosis in Western countries and manifests mainly as progressive restrictive cardiomyopathy.

    Objective: To study the prevalence of ATTR deposits in ligament tissue in patients undergoing surgery for lumbar spinal stenosis and to assess whether these deposits are associated with cardiac amyloidosis.

    Materials and methods: A total of 250 patients, aged 50–89 (57% women), none with known cardiovascular disease, were included. Ligaments were investigated microscopically for amyloid. ATTR type was determined by immunohistochemistry and fibril type by Western blot. The amount of amyloid was graded 0‐4. All patients with grade 3‐4 ATTR deposits were offered cardiac investigation including ECG, cardiac ultrasound, plasma NT‐proBNP and cardiac magnetic resonance (CMR), including modern tissue characterization.

    Results: Amyloid was identified in 221 of the samples (88.4%). ATTR appeared in 93 samples (37%) of whom 42 (17 women and 25 men) were graded 3‐4; all had fibril type A (mixture of full‐length TTR and fragmented TTR). Twenty‐nine of 42 patients with grade 3‐4 ATTR deposits accepted cardiovascular investigations; none of them had definite signs of cardiac amyloidosis, but five men had a history of carpal tunnel syndrome.

    Conclusions: The prevalence of ATTR deposits in ligamentum flavum in patients with lumbar spinal stenosis was high but not associated with manifest ATTR cardiac amyloidosis. However, the findings of fibril type A, the prevalence of previous carpal tunnel syndrome and ATTR amyloid in surrounding adipose and vascular tissue indicate that amyloid deposits in ligamentum flavum may be an early manifestation of systemic ATTR disease.

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  • 26. 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.

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  • 27. 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.

  • 28.
    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.

  • 29.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    The endocannabinoid system – current implications for drug development2021In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 290, no 1, p. 2-26Article, review/survey (Refereed)
    Abstract [en]

    In this review, the state of the art for compounds affecting the endocannabinoid (eCB) system is described with a focus on the treatment of pain. Amongst directly acting CB receptor ligands, clinical experience with ∆9-tetrahydracannabinol and medical cannabis in chronic non-cancer pain indicates that there are differences between the benefits perceived by patients and the at best modest effect seen in meta-analyses of randomized controlled trials. The reason for this difference is not known but may involve differences in the type of patients that are recruited, the study conditions that are chosen and the degree to which biases such as reporting bias are operative. Other directly acting CB receptor ligands such as biased agonists and allosteric receptor modulators have not yet reached the clinic. Amongst indirectly acting compounds targeting the enzymes responsible for the synthesis and catabolism of the eCBs anandamide and 2-arachidonoylglycerol, fatty acid amide hydrolase (FAAH) inhibitors have been investigated clinically but were per se not useful for the treatment of pain, although they may be useful for the treatment of post-traumatic stress disorder and cannabis use disorder. Dual-acting compounds targeting this enzyme and other targets such as cyclooxygenase-2 or transient potential vanilloid receptor 1 may be a way forward for the treatment of pain.

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  • 30.
    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.

  • 31.
    Franks, P.W.
    et al.
    From the, Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, MA, Boston, United States.
    Melén, E.
    Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Friedman, M.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Sundström, J.
    Department of Cardiology, Akademiska Sjukhuset, Uppsala, Sweden; George Institute for Global Health, NSW, Camperdown, Australia; Medical Sciences, Uppsala University, Uppsala, Sweden.
    Kockum, I.
    Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Klareskog, L.
    Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Rheumatology, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, C.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bergen, S.E.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Czene, K.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Hägg, S.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Hall, P.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Oncology, Södersjukhuset, Stockholm, Sweden.
    Johnell, K.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Malarstig, A.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Pfizer, Worldwide Research and Development, Stockholm, Sweden.
    Catrina, A.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hagström, H.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.
    Benson, M.
    Department of Pediatrics, Linkopings Universitet, Linkoping, Sweden; Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
    Gustav Smith, J.
    Department of Cardiology and Wallenberg Center for Molecular Medicine, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University and Sahlgrenska University Hospital, Gothenburg, Sweden.
    Gomez, M.F.
    From the, Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Orho-Melander, M.
    From the, Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Jacobsson, B.
    Division of Health Data and Digitalisation, Norwegian Institute of Public Health, Genetics and Bioinformatics, Oslo, Norway; Department of Obstetrics and Gynecology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
    Halfvarson, J.
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Repsilber, D.
    Functional Bioinformatics, Örebro University, Örebro, Sweden.
    Oresic, M.
    School of Medical Sciences, Örebro University, Örebro, Sweden; Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI, Turku, Finland.
    Jern, C.
    Department of Clinical Genetics and Genomics, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ohlsson, C.
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, CBAR, University of Gothenburg, Gothenburg, Sweden; Department of Drug Treatment, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Fall, T.
    Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
    Rönnblom, L.
    Department of Medical Sciences, Rheumatology & Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Wadelius, M.
    Department of Medical Sciences, Clinical Pharmacogenomics & Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Nordmark, G.
    Department of Medical Sciences, Rheumatology & Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Johansson, Å.
    Institute for Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
    Rosenquist, R.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Sullivan, P.F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Genetics, University of North Carolina at Chapel Hill, NC, Chapel Hill, United States; Department of Psychiatry, University of North Carolina at Chapel Hill, NC, Chapel Hill, United States.
    Technological readiness and implementation of genomic-driven precision medicine for complex diseases2021In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 290, no 3, p. 602-620Article, review/survey (Refereed)
    Abstract [en]

    The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment – genomic-driven precision medicine (GDPM) – may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.

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  • 32.
    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.

  • 33. Goedecke, J. H.
    et al.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Pathogenesis of type 2 diabetes risk in black Africans: a South African perspective2020In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 288, no 3, p. 284-294Article in journal (Refereed)
    Abstract [en]

    The prevalence of type 2 diabetes (T2D) is higher in black Africans than their European counterparts. This review summarizes the research exploring the pathogenesis of T2D in populations of African ancestry compared to white Europeans and shows that the pathogenesis differs by ethnicity. Black Africans present with a phenotype of low insulin sensitivity and hyperinsulinaemia as a result of increased insulin secretion and reduced hepatic insulin clearance. Whether hyperinsulinaemia precedes insulin resistance or is merely a compensatory mechanism is yet to be determined. Black Africans have lower visceral adipose tissue and ectopic fat deposition and greater peripheral (gluteo-femoral) fat deposition than their European counterparts. This suggests that black Africans are more sensitive to the effects of ectopic fat deposition, or alternatively, that ectopic fat is not an important mediator of T2D in black Africans. Importantly, ethnic disparities in T2D risk factors may be confounded by differences in sociocultural and lifestyle factors. Future longitudinal and dietary intervention studies, in combination with genetic analyses, are needed for a better understanding of the pathophysiology of T2D in black Africans. This will be key for effective prevention and management strategies.

  • 34. 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)
  • 35. 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.

  • 36.
    Hariz, Marwan
    et al.
    Department of Clinical Neuroscience, University Hospital of Umeå, Umeå, Sweden; 2UCL-Queen Square Institute of Neurology, London, UK.
    Blomstedt, Patric
    Department of Clinical Neuroscience, University Hospital of Umeå, Umeå, Sweden.
    Deep brain stimulation for Parkinson's disease2022In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 292, no 5, p. 764-778Article in journal (Refereed)
    Abstract [en]

    Parkinson's disease (PD) is a progressive neurodegenerative illness with both motor and nonmotor symptoms. Deep brain stimulation (DBS) is an established safe neurosurgical symptomatic therapy for eligible patients with advanced disease in whom medical treatment fails to provide adequate symptom control and good quality of life, or in whom dopaminergic medications induce severe side effects such as dyskinesias. DBS can be tailored to the patient's symptoms and targeted to various nodes along the basal ganglia-thalamus circuitry, which mediates the various symptoms of the illness; DBS in the thalamus is most efficient for tremors, and DBS in the pallidum most efficient for rigidity and dyskinesias, whereas DBS in the subthalamic nucleus (STN) can treat both tremors, akinesia, rigidity and dyskinesias, and allows for decrease in doses of medications even in patients with advanced stages of the disease, which makes it the preferred target for DBS. However, DBS in the STN assumes that the patient is not too old, with no cognitive decline or relevant depression, and does not exhibit severe and medically resistant axial symptoms such as balance and gait disturbances, and falls. Dysarthria is the most common side effect of DBS, regardless of the brain target. DBS has a long-lasting effect on appendicular symptoms, but with progression of disease, nondopaminergic axial features become less responsive to DBS. DBS for PD is highly specialised; to enable adequate selection and follow-up of patients, DBS requires dedicated multidisciplinary teams of movement disorder neurologists, functional neurosurgeons, specialised DBS nurses and neuropsychologists.

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  • 37.
    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.

  • 38.
    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.

  • 39.
    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)
  • 40.
    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.

  • 41.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Introduction The 99th Berzelius symposium: the Cardiac Patient from Birth to Adulthood2020In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 288, no 4, p. 381-382Article in journal (Other academic)
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  • 42.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Örtendahl, Lina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lind, Marcus M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Brunström, Mattias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Diabetes, prediabetes, and atrial fibrillation: a population-based cohort study based on national and regional registers2023In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 294, no 5, p. 605-615Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies have shown an increased risk for atrial fibrillation and atrial flutter (AF) in people with type 2 diabetes and prediabetes. It is unclear whether this increase in AF risk is independent of other risk factors for AF.

    Objective: To investigate the association between diabetes and different prediabetic states, as independent risk factors for the onset of AF.

    Methods: We performed a population-based cohort study in Northern Sweden, including data on fasting plasma glucose, oral glucose tolerance test, major cardiovascular risk factors, medical history, and lifestyle factors. Participants were divided into six groups depending on glycemic status and followed through national registers for AF diagnosis. Cox proportional hazard model was used to assess the association between glycemic status and AF, using normoglycemia as reference.

    Results: The cohort consisted of 88,889 participants who underwent a total of 139,661 health examinations. In the model adjusted for age and sex, there was a significant association between glycemic status and development of AF in all groups except the impaired glucose tolerance group, with the strongest association for the group with known diabetes (p-value <0.001). In a model adjusted for sex, age, systolic blood pressure, body mass index, antihypertensive drugs, cholesterol, alcohol, smoking, education level, marital status, and physical activity, there was no significant association between glycemic status and AF.

    Conclusions/interpretation: The association between glycemic status and AF disappears upon adjustment for potential confounders. Diabetes and prediabetes do not appear to be independent risk factors for AF.

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  • 43.
    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.

  • 44.
    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.

  • 45.
    Johansson, Åsa
    et al.
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Andreassen, Ole A.
    NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopment Research, University of Oslo, Oslo, Norway.
    Brunak, Søren
    Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Rigshospitalet, Blegdamsvej 9, Copenhagen University Hospital, Copenhagen, Denmark.
    Franks, Paul W.
    Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Science, Lund University, Lund, Sweden; Novo Nordisk Foundation, Hellerup, Denmark.
    Hedman, Harald
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Loos, Ruth J. F.
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Charles Bronfman Institute for Personalized Medicine at Mount Sinai, Icahn School of Medicine at Mount Sinai, NY, New York, United States.
    Meder, Benjamin
    Precision Digital Health, Cardiogenetics Center Heidelberg, Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
    Melén, Erik
    Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
    Wheelock, Craig E.
    Unit of Integrative Metabolomics, Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.
    Jacobsson, Bo
    Department of Obstetrics and Gynecology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Genetics and Bioinformatics, Domain of Health Data and Digitalisation, Institute of Public Health, Oslo, Norway.
    Precision medicine in complex diseases—Molecular subgrouping for improved prediction and treatment stratification2023In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 294, no 4, p. 378-396Article, review/survey (Refereed)
    Abstract [en]

    Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease—both with regards to symptoms and underlying causal mechanisms—and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases—including psychiatric disorders and allergies—available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.

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  • 46. 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.

  • 47. Keyser, P.
    et al.
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Rosell, S.
    Wolf-Watz, Hans
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Virulence blockers as alternatives to antibiotics: type III secretion inhibitors against Gram-negative bacteria2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 264, no 1, p. 17-29Article in journal (Refereed)
    Abstract [en]

    In recent years mounting problems related to antibiotic-resistant bacteria have resulted in the prediction that we are entering the preantibiotic era. A way of preventing such a development would be to introduce novel antibacterial medicines with modes of action distinct from conventional antibiotics. Recent studies of bacterial virulence factors and toxins have resulted in increased understanding of the way in which pathogenic bacteria manipulate host cellular processes. This knowledge may now be used to develop novel antibacterial medicines that disarm pathogenic bacteria. The type III secretion system (T3SS) is known to be a potent virulence mechanism shared by a broad spectrum of pathogenic Gram-negative bacteria that interact with human, animal and plant hosts by injecting effector proteins into the cytosol of host cells. Diseases, such as bubonic plague, shigellosis, salmonellosis, typhoid fever, pulmonary infections, sexually transmitted chlamydia and diarrhoea largely depend on the bacterial proteins injected by the T3SS machinery. Recently a number of T3SS inhibitors have been identified using screening-based approaches. One class of inhibitors, the salicylidene acylhydrazides, has been subjected to chemical optimization and evaluation in several in vitro and ex vivo assays in multiple bacterial species including Yersinia spp., Chlamydia spp., Salmonella spp. and Pseudotuberculosis aeruginosa. Reports published up to date indicate that T3SS inhibitors have the potential to be developed into novel antibacterial therapeutics.

  • 48. 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.

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  • 49. 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.

  • 50.
    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.

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