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  • 1.
    Adamsson, Viola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Reumark, A.
    Fredriksson, I. -B
    Hammarström, E.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Johansson, G.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects: a randomized controlled trial (NORDIET)2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 2, p. 150-159Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to investigate the effects of a healthy Nordic diet (ND) on cardiovascular risk factors. Design and subjects. In a randomized controlled trial (NORDIET) conducted in Sweden, 88 mildly hypercholesterolaemic subjects were randomly assigned to an ad libitum ND or control diet (subjects' usual Western diet) for 6 weeks. Participants in the ND group were provided with all meals and foods. Primary outcome measurements were low-density lipoprotein (LDL) cholesterol, and secondary outcomes were blood pressure (BP) and insulin sensitivity (fasting insulin and homeostatic model assessment-insulin resistance). The ND was rich in high-fibre plant foods, fruits, berries, vegetables, whole grains, rapeseed oil, nuts, fish and low-fat milk products, but low in salt, added sugars and saturated fats. Results. The ND contained 27%, 52%, 19% and 2% of energy from fat, carbohydrate, protein and alcohol, respectively. In total, 86 of 88 subjects randomly assigned to diet completed the study. Compared with controls, there was a decrease in plasma cholesterol (-16%, P < 0.001), LDL cholesterol (-21%, P < 0.001), high-density lipoprotein (HDL) cholesterol (-5%, P < 0.01), LDL/HDL (-14%, P < 0.01) and apolipoprotein (apo)B/apoA1 (-1%, P < 0.05) in the ND group. The ND reduced insulin (-9%, P = 0.01) and systolic BP by -6.6 +/- 13.2 mmHg (-5%, P < 0.05) compared with the control diet. Despite the ad libitum nature of the ND, body weight decreased after 6 weeks in the ND compared with the control group (-4%, P < 0.001). After adjustment for weight change, the significant differences between groups remained for blood lipids, but not for insulin sensitivity or BP. There were no significant differences in diastolic BP or triglyceride or glucose concentrations. Conclusions. A healthy ND improves blood lipid profile and insulin sensitivity and lowers blood pressure at clinically relevant levels in hypercholesterolaemic subjects.

  • 2.
    Adamsson, Viola
    et al.
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Reumark, Anna
    Lantmännen R and D, Stockholm, Sweden.
    Fredriksson, I.-B.
    Bollnäs Heart Clinic, Mitt Hjärta, Bollnäs, Sweden.
    Hammarström, Eskil
    Bollnäs Heart Clinic, Mitt Hjärta, Bollnäs, Sweden.
    Vessby, Bengt
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Johansson, Gunnar
    Halmstad University, School of Health and Welfare, Centre of Research on Welfare, Health and Sport (CVHI).
    Riserus, U.
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects: a randomized controlled trial (NORDIET)2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 2, p. 150-159Article in journal (Refereed)
    Abstract [en]

    Objective:

    The aim of this study was to investigate the effects of a healthy Nordic diet (ND) on cardiovascular risk factors.

    Design and subjects:

    In a randomizedcontrolled trial (NORDIET) conducted in Sweden, 88 mildly hypercholesterolaemic subjects were randomly assigned to an ad libitum ND or control diet (subjects' usual Western diet) for 6 weeks. Participants in the ND group were provided with all meals and foods. Primary outcome measurements were low-density lipoprotein (LDL) cholesterol, and secondary outcomes were blood pressure (BP) and insulin sensitivity (fasting insulin and homeostatic model assessment-insulin resistance). The ND was rich in high-fibre plant foods, fruits, berries, vegetables, whole grains, rapeseed oil, nuts, fish and low-fat milk products, but low in salt, added sugars and saturated fats.

    Results:

    The ND contained 27%, 52%, 19% and 2% of energy from fat, carbohydrate, protein and alcohol, respectively. In total, 86 of 88 subjects randomly assigned to diet completed the study. Compared with controls, there was a decrease in plasma cholesterol (-16%, P < 0.001), LDL cholesterol (-21%, P < 0.001), high-density lipoprotein (HDL) cholesterol (-5%, P < 0.01), LDL/HDL (-14%, P < 0.01) and apolipoprotein (apo)B/apoA1 (-1%, P < 0.05) in the ND group. The ND reduced insulin (-9%, P = 0.01) and systolic BP by -6.6 ± 13.2 mmHg (-5%, P < 0.05) compared with the control diet. Despite the ad libitum nature of the ND, body weight decreased after 6 weeks in the ND compared with the control group (-4%, P < 0.001). After adjustment for weight change, the significant differences between groups remained for blood lipids, but not for insulin sensitivity or BP. There were no significant differences in diastolic BP or triglyceride or glucose concentrations.

    Conclusions:

    A healthy ND improves blood lipid profile and insulin sensitivity and lowers blood pressure at clinically relevant levels in hypercholesterolaemic subjects. © 2010 The Association for the Publication of the Journal of Internal Medicine.

  • 3.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Ekermo, Bengt
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Transfusion Medicine and Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Månsson, A-S.
    Department of Clinical Virology, University Hospital of Malmö, Sweden.
    Svensson, Samuel
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Widell, A.
    Department of Clinical Virology, University Hospital of Malmö, Sweden.
    Detection and prevention of hepatitis C in dialysis patients and renal transplant recipients: A long-term follow up (1989–January 1997)2002In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 251, no 2, p. 119-128Article in journal (Refereed)
    Abstract [en]

    Background. Hepatitis C is frequent problem in dialysis wards.

    Design.  A long time (1989–97) follow up of hepatitis C virus (HCV) infection in a Swedish nephrology unit was performed with anti-HCV screening, confirmatory antibody tests, viral RNA detection and molecular characterization. Case histories were reviewed with focus, onset of infection, liver morbidity and mortality.

    Results.  In October 1991, 10% (19 of 184) of the patients in the unit (haemodialysis-, peritoneal dialysis and transplanted patients) were verified or suspected HCV carriers, whilst the number at the end of 1996 was 8% (13 of 157). Most patients were infected before 1991 but only in one case from a known HCV-infected blood donor. No new HCV infections associated with haemodialysis occurred during the study period. A total of 13 of 24 viremic patients had HCV genotype 2b, a pattern suggesting nosocomial transmission. This was further supported by phylogenetic analysis of HCV viral isolates in seven. HCV viremia was also common in patients with an incomplete anti-HCV antibody pattern as 8 of the 12 indeterminant sera were HCV-RNA positive.

    Conclusions.  Awareness, prevention, identification of infected patients and donor testing limited transmission. Indeterminant recombinant immunoblot assays (RIBA)-results should be regarded with caution as a result of the relative immunodeficiency in uremic patients. Our data indicate nosocomial transmission in several patients.

  • 4.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Nephrology.
    Eneström, S.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Hed, J.
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Transfusion Medicine and Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Samuelsson, I.
    Section of Nephrology, Department of Internal Medicine. Örebro Medical Centre, Örebro, Sweden.
    Sjöström, P.
    Section of Nephrology, Department of Internal Medicine. Örebro Medical Centre, Örebro, Sweden.
    Autoantibodies to leucocyte antigens in hydralazine-associated nephritis1992In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 231, no 1, p. 37-42Article in journal (Refereed)
    Abstract [en]

    Clinical and laboratory findings and drug history were studied in 17 patients with suspected hydralazine-associated nephritis, five of whom only had renal disease, while twelve also had extrarenal manifestations. Renal biopsies revealed extracapillary proliferative or focal segmental proliferative glomerulonephritis in 10 patients, and tubulo-interstitial nephritis in five patients. Antinuclear antibody (ANA) was found in 16 patients, but none of the 14 patients tested had antibodies to DNA. Tests for antibodies to myeloperoxidase (anti-MPO) and antibodies to neutrophil cytoplasm antigen (ANCA) were performed by ELISA. Twelve of the 14 patients tested had anti-MPO; five of these 14 patients had ANCA, while one had borderline levels. These findings suggest that hydralazine facilitates the induction of a systemic disease with multiple autoantibody production.

  • 5.
    Almroth, Gabriel
    et al.
    Section of Nephrology, Department of Internal Medicine, Medical Centre Hospital, Örebro.
    Sjöström, P.
    Section of Nephrology, Department of Internal Medicine, Medical Centre Hospital, Örebro.
    Svalander, C.
    Department of Pathology, Sahlgren's Hospital, University of Göteborg, Sweden.
    Danielsson, D.
    Department of Microbiology and Immunology, Medical Centre Hospital, Örebro.
    Serum immunoglobulins and IgG subclasses in patients with glomerulonephritis1989In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 225, no 1, p. 3-7Article in journal (Refereed)
    Abstract [en]

    The serum concentrations of IgG, IgA, IgM and of the four subclasses of IgG were determined by radial immunodiffusion in 103 patients, mean age 42 (range 16–72), with various types of glomerulonephritis. Forty-nine healthy blood donors, mean age 41 years (range 19–65), served as controls. Kidney biopsies were obtained from all the patients for examination by histopathology and by immunofluorescence. The glomerulopathies were classified according to WHO criteria.

    The serum immunoglobulin patterns were different for the various clinical groups of patients. Patients with Wegener's granulomatosis, rapidly progressive glomerulonephritis and SLE had a significant increase in total IgG and of IgG4 (P < 0.05–0.001). Patients with minimal change disease had low concentrations of IgG (P < 0.001) with a significant decrease in IgG1 and IgG2 (P < 0.001 and 0.01. respectively). Highly significant increases in IgA were noted for patients with IgA nephritis (P < 0.001) but high levels were also seen in patients with chronic glomerulonephritis. The findings might have diagnostic implications.

  • 6.
    Almroth, Henrik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Torbjorn
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Fengsrud, Espen
    Örebro University, School of Health Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Friberg, Leif
    Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Linde, P.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Rosenqvist, Mårten
    Stockholm South Hospital, Karolinska Institutet, Stockholm, Sweden.
    Englund, A.
    Stockholm South Hospital, Karolinska Institutet, Stockholm, Sweden.
    The safety of flecainide treatment of atrial fibrillation: long-term incidence of sudden cardiac death and proarrhythmic events2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 3, p. 281-290Article in journal (Refereed)
    Abstract [en]

    Objective:To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) andproarrhythmic events.

    Design: Retrospective,observational cohort study.Setting.Single-centre study at Örebro University Hospital, Sweden.

    Setting: Single-centre study at Orebro University Hospital, Sweden.

    Subjects: A total of 112 patients with paroxysmal (51%) or persistent (49%) AF (mean age 60 ± 11 years) were included after identifying all patients with AF who initiated oral flecainide treatment (mean dose 203 ± 43 mg per day) between 1998 and 2006. Standard exclusion⁄inclusion criteria for flecainide were used,andflecainidetreatmentwasusually combined withanatrioventricular-blocking agent (89%).

    Main outcome measure: Death was classified as sudden or nonsudden according to standard definitions. Proarrhythmia was defined as cardiac syncope or lifethreatening arrhythmia.

    Results: Eight deaths were reported during a mean follow- up of 3.4 ± .4 years. Compared to the general population, the standardized mortality ratios were 1.57 (95% confidence interval (CI) 0.68–3.09) for allcause mortality and 4.16 (95% CI 1.53–9.06) for death from cardiovascular disease. Three deaths were classified as SCDs. Proarrhythmic events occurred in six patients (two each with wide QRS tachycardia, 1 : 1 conducted atrial flutter and syncope during exercise).

    Conclusion: We found an increased incidence of SCD or proarrhythmic events in this real-world study of flecainide used for the treatment of AF. The findings suggest that further investigation into the safety of flecainide for the treatment of patients with AF is warranted.

  • 7.
    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.

  • 8.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rasmussen, F.
    Lund Univ, Dept Hlth Sci, Lund, Sweden.
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Tynelius, P.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden;Stockholm Cty Council, Ctr Epidemiol & Community Med, Stockholm, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Body size and risk of atrial fibrillation: a cohort study of 1.1 million young men2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 346-355Article in journal (Refereed)
    Abstract [en]

    Background: Whilst tall stature has been related to lower risk of vascular disease, it has been proposed as a risk factor for atrial fibrillation. Little is known about other anthropometric measures and their joint effects on risk of atrial fibrillation.

    Objectives: We aim to investigate associations and potential joint effects of height, weight, body surface area (BSA) and body mass index (BMI) with risk of atrial fibrillation.

    Methods: In a cohort covering 1 153 151 18-year-old men participating in the Swedish military conscription (1972-1995), Cox regression was used to investigate associations of height, weight, BSA and BMI with risk of atrial fibrillation.

    Results: During a median of 26.3 years of follow-up, higher height was associated with higher risk of atrial fibrillation (hazard ratio [HR] 2.80; 95% CI 2.63-2.98; for 5th vs. 1st quintile) and so was larger BSA (HR 3.05; 95% CI 2.82-3.28; for 5th vs. 1st quintile). Higher weight and BMI were to a lesser extent associated with risk of atrial fibrillation (BMI: 1.42; 95% CI 1.33-1.52, for 5th vs. 1st quintile). We found a multiplicative joint effect of height and weight. Adjusting for muscle strength, exercise capacity and diseases related to atrial fibrillation attenuated these measures.

    Conclusions: Higher height and weight are strongly associated with higher risk of atrial fibrillation. These associations are multiplicative and independent of each other and are summarized in a strong association of body surface area with risk of atrial fibrillation. The mechanisms remain unknown but may involve increased atrial volume load with larger body size.

  • 9.
    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.

  • 10.
    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.

  • 11.
    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.

  • 12.
    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)
  • 13.
    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.

  • 14.
    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)
  • 15.
    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.

  • 16.
    Andersson, I.
    et al.
    Obesity Unit, Huddinge University Hospital, Huddinge, Sweden.
    Lennernäs, Maria
    Swedish Dairy Association, Stockholm, Sweden.
    Rössner, Stefan
    Obesity Unit, Huddinge University Hospital, Huddinge, Sweden.
    Meal pattern and risk factor evaluation in one-year completers of a weight reduction program for obese men - the "Gustaf" study2000In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 247, p. 30-38Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate changes in meal patterns and in obesity related risk factors after 1 year of treatment in obese men. Design: Data from two 24-h dietary recalls, performed at base-line and after 1 year of treatment, were related to changes in medical risk factors. Setting: Academic obesity unit. Subjects: Sixty-three men, aged 44 (eight) years (mean [SD]) and Base- line Body Mass Index (BMI) 37.4 (4.6) kg m-2, who had completed 1 year of treatment. The men were subdivided by tertiles according to weight change: tertile I (n = 21), mean +0.3 kg, tertile II (n = 21), mean -5.8 kg and tertile III (n = 21), mean -14.2 kg. Main outcome measures: Weight loss, changes in meal patterns and in obesity related medical risk factors. Results: The reported mean energy intake decreased after treatment in tertiles II and III by 700 (1300) kcal (P < 0.05) and 700 (900) kcal (P = 0.001), respectively. In tertile III the energy-% from fat decreased (P < 0.05) with a reciprocal increase in energy-% from protein (P < 0.05). The frequency of snacks of a low nutritional quality decreased (P < 0.01) in tertile III together with an increase in energy-% from 'hot meals of good quality' (P < 0.05). Obesity related risk factors (anthropometry, blood pressure, serum lipid concentrations, blood glucose and plasma insulin) improved in a beneficial way only in tertile III. Conclusions: The weight loss in the successful tertile III men was to a great extent explained by fewer low quality snacks but more energy from high quality meals. These changes reflected the behaviour modification strategy recommended.

  • 17.
    Andersson, Ingalena
    et al.
    Obesity Unit, M73, Huddinge University Hospital.
    Wiklund, Maria Lennernäs
    Swedish Dairy Association, Karolinska Institute.
    Rössner, Stephan
    Obesity Unit, M73, Huddinge University Hospital.
    Meal pattern and risk factor evaluation in one-year completers of a weight reduction program for obese men: The 'Gustaf' study2000In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 247, no 1, p. 30-38Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate changes in meal patterns and in obesity related risk factors after 1 year of treatment in obese men. Design: Data from two 24-h dietary recalls, performed at base-line and after 1 year of treatment, were related to changes in medical risk factors. Setting: Academic obesity unit. Subjects: Sixty-three men, aged 44 (eight) years (mean [SD]) and Base- line Body Mass Index (BMI) 37.4 (4.6) kg m-2, who had completed 1 year of treatment. The men were subdivided by tertiles according to weight change: tertile I (n = 21), mean +0.3 kg, tertile II (n = 21), mean -5.8 kg and tertile III (n = 21), mean -14.2 kg. Main outcome measures: Weight loss, changes in meal patterns and in obesity related medical risk factors. Results: The reported mean energy intake decreased after treatment in tertiles II and III by 700 (1300) kcal (P < 0.05) and 700 (900) kcal (P = 0.001), respectively. In tertile III the energy-% from fat decreased (P < 0.05) with a reciprocal increase in energy-% from protein (P < 0.05). The frequency of snacks of a low nutritional quality decreased (P < 0.01) in tertile III together with an increase in energy-% from 'hot meals of good quality' (P < 0.05). Obesity related risk factors (anthropometry, blood pressure, serum lipid concentrations, blood glucose and plasma insulin) improved in a beneficial way only in tertile III. Conclusions: The weight loss in the successful tertile III men was to a great extent explained by fewer low quality snacks but more energy from high quality meals. These changes reflected the behaviour modification strategy recommended.

  • 18.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    How selective sweeps in domestic animals provide new insight into biological mechanisms2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 271, no 1, p. 1-14Article, review/survey (Refereed)
    Abstract [en]

    Genetic studies of domestic animals are of general interest because there is more phenotypic diversity to explore in these species than in any experimental organism. Some mutations with favourable phenotypic effects have been highly enriched and gone through selective sweeps during the process of domestication and selective breeding. Three such selective sweeps are described in this review. All three mutations are intronic and constitute cis-acting regulatory mutations. Two of the mutations constitute structural changes (one duplication and one copy number expansion). These examples illustrate a general trend that noncoding mutations and structural changes have both contributed significantly to the evolution of phenotypic diversity in domestic animals. How the molecular characterization of trait loci in domestic animals can provide new basic knowledge of relevance for human medicine is discussed.

  • 19. Andersson, P.
    et al.
    Londahl, M.
    Abdon, N. -J
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    The prevalence of atrial fibrillation in a geographically well-defined population in Northern Sweden: implications for anticoagulation prophylaxis2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 272, no 2, p. 170-176Article in journal (Refereed)
    Abstract [en]

    Objectives. The aims of this study were to evaluate the community-based prevalence of atrial fibrillation (AF) in a western society using a geographically well-defined population in the northern part of Sweden as a reference and to estimate the proportion of patients eligible for oral anticoagulation (OAC) prophylactic therapy according to the stroke risk indices CHADS2 and CHA2DS2-VASc. Bleeding risk was assessed using the HAS-BLED score.

    Design. The study population was recruited from AURICULA, a Swedish national quality register for patients receiving anticoagulation treatment. All patients with the diagnosis AF in the catchment area are registered in AURICULA.

    Results. Of the 65 532 inhabitants in the catchment area, 1616 were diagnosed with AF (1200 cases were characterized as chronic AF). Thus, the overall prevalence of AF was 2.5%. The prevalence increased with age from 6.3% in patients over 55 years of age to 13.8% in those over 80 years. The prevalence was higher in men than in women in all age groups. Overall, 56.3% and 85.1% of the population were at high risk of stroke (=2 points) according to CHADS2 and CHA2DS2-VASc, respectively. In addition, 26.9% had an increased bleeding risk according to HAS-BLED.

    Conclusion. Within this large Caucasian population, we identified the highest community-based prevalence of AF to date. The prevalence was strongly associated with increasing age and male gender. Using CHA2DS2-VASc instead of CHADS2 widened the indication for OAC prophylactic therapy of AF in this population.

  • 20.
    Angelin, Bo
    et al.
    Karolinska University, Sweden; Karolinska University, Sweden.
    Kristensen, Jens D.
    Karo Bio AB, Sweden.
    Eriksson, Mats
    Karolinska University, Sweden; Karolinska University, Sweden.
    Carlsson, Bo
    Karo Bio AB, Sweden.
    Klein, Irwin
    NYU, NY USA.
    Olsson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Stockholm Heart Centre, Sweden.
    Chester Ridgway, E.
    University of Colorado, CO USA.
    Ladenson, Paul W.
    Johns Hopkins University, MD 21205 USA.
    Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 3, p. 331-342Article in journal (Refereed)
    Abstract [en]

    BackgroundLiver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia. MethodsWe performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200gday(-1) eprotirome or placebo for 12weeks. The primary end-point was change in serum LDL cholesterol; secondary end-points included changes in other lipid parameters and safety measures. ResultsEprotirome treatment at 100 and 200g daily reduced serum LDL cholesterol levels by 235% and 31 +/- 4%, respectively, compared with 2 +/- 6% for placebo (Pless than0.0001). Similar reductions were seen in non-HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A-I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low-grade increases in liver enzymes were evident in most patients. ConclusionIn hypercholesterolaemic patients, the liver-selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra-hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.

  • 21.
    Ankarcrona, M.
    et al.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Ctr Alzheimer Res, Huddinge, Sweden..
    Winblad, B.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Ctr Alzheimer Res, Huddinge, Sweden..
    Monteiro, C.
    Skaggs Inst Chem Biol, Dept Chem, La Jolla, CA 92037 USA.;Scripps Res Inst, Dept Mol & Expt Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA..
    Fearns, C.
    Skaggs Inst Chem Biol, Dept Chem, La Jolla, CA 92037 USA.;Scripps Res Inst, Dept Mol & Expt Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA..
    Powers, E. T.
    Skaggs Inst Chem Biol, Dept Chem, La Jolla, CA 92037 USA..
    Johansson, J.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Ctr Alzheimer Res, Huddinge, Sweden..
    Westermark, Gunilla T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Presto, J.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Ctr Alzheimer Res, Huddinge, Sweden..
    Ericzon, B. -G
    Karolinska Univ Hosp, Div Transplantat Surg, Stockholm, Sweden.
    Kelly, J. W.
    Skaggs Inst Chem Biol, Dept Chem, La Jolla, CA 92037 USA.;Scripps Res Inst, Dept Mol & Expt Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA..
    Current and future treatment of amyloid diseases2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 280, no 2, p. 177-202Article, review/survey (Refereed)
    Abstract [en]

    There are more than 30 human proteins whose aggregation appears to cause degenerative maladies referred to as amyloid diseases or amyloidoses. These disorders are named after the characteristic cross--sheet amyloid fibrils that accumulate systemically or are localized to specific organs. In most cases, current treatment is limited to symptomatic approaches and thus disease-modifying therapies are needed. Alzheimer's disease is a neurodegenerative disorder with extracellular amyloid -peptide (A) fibrils and intracellular tau neurofibrillary tangles as pathological hallmarks. Numerous clinical trials have been conducted with passive and active immunotherapy, and small molecules to inhibit A formation and aggregation or to enhance A clearance; so far such clinical trials have been unsuccessful. Novel strategies are therefore required and here we will discuss the possibility of utilizing the chaperone BRICHOS to prevent A aggregation and toxicity. Type 2 diabetes mellitus is symptomatically treated with insulin. However, the underlying pathology is linked to the aggregation and progressive accumulation of islet amyloid polypeptide as fibrils and oligomers, which are cytotoxic. Several compounds have been shown to inhibit islet amyloid aggregation and cytotoxicity in vitro. Future animal studies and clinical trials have to be conducted to determine their efficacy in vivo. The transthyretin (TTR) amyloidoses are a group of systemic degenerative diseases compromising multiple organ systems, caused by TTR aggregation. Liver transplantation decreases the generation of misfolded TTR and improves the quality of life for a subgroup of this patient population. Compounds that stabilize the natively folded, nonamyloidogenic, tetrameric conformation of TTR have been developed and the drug tafamidis is available as a promising treatment. Read more articles from the symposium: Amyloid - a multifaceted player in human health and disease.

  • 22.
    Arama, Charles
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Sciences Techniques and Technologies of Bamako, Mali.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    The path of malaria vaccine development: challenges and perspectives2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, no 5, p. 456-466Article, review/survey (Refereed)
    Abstract [en]

    Malaria is a life-threatening disease caused by parasites of the Plasmodium genus. In many parts of the world, the parasites have developed resistance to a number of antimalarial agents. Key interventions to control malaria include prompt and effective treatment with artemisinin-based combination therapies, use of insecticidal nets by individuals at risk and active research into malaria vaccines. Protection against malaria through vaccination was demonstrated more than 30years ago when individuals were vaccinated via repeated bites by Plasmodium falciparum-infected and irradiated but still metabolically active mosquitoes. However, vaccination with high doses of irradiated sporozoites injected into humans has long been considered impractical. Yet, following recent success using whole-organism vaccines, the approach has received renewed interest; it was recently reported that repeated injections of irradiated sporozoites increased protection in 80 vaccinated individuals. Other approaches include subunit malaria vaccines, such as the current leading candidate RTS,S (consisting of fusion between a portion of the P.falciparum-derived circumsporozoite protein and the hepatitis B surface antigen), which has been demonstrated to induce reasonably good protection. Although results have been encouraging, the level of protection is generally considered to be too low to achieve eradication of malaria. There is great interest in developing new and better formulations and stable delivery systems to improve immunogenicity. In this review, we will discuss recent strategies to develop efficient malaria vaccines.

  • 23.
    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)
  • 24.
    Axelsson, K. F.
    et al.
    Department of Orthopaedic Surgery, Skaraborg Hospital, Skövde, Sweden / Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Wallander, M.
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden / Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
    Johansson, H.
    Institute for Health and Ageing, Catholic University of Australia, Melbourne, Vic., Australia.
    Lundh, Dan
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Lorentzon, M.
    Geriatric Medicine, Department of Internal Medicine and ClinicalNutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden / Geriatric Medicine, Sahlgrenska University Hospital, Mölndal, Sweden.
    Hip fracture risk and safety with alendronate treatment in the oldest-old2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, no 6, p. 546-559Article in journal (Refereed)
    Abstract [en]

    Background. There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate's efficacy to prevent hip fractures in the oldest-old (80 years old), the population with the highest fracture risk, has not been studied. Objective. To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety. Methods. Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term. Results. The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49-0.79), P < 0.001) and multivariable models (HR 0.66 (0.51-0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82-0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12-2.24). The alendronate association did not change with age for hip fractures or mild UGI. Conclusion. In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patients.

  • 25.
    Axelsson, K. F.
    et al.
    Department of Orthopaedic Surgery, Skaraborg Hospital, Skövde, Sweden.
    Wallander, M.
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Johansson, H.
    Institute for Health and Ageing, Catholic University of Australia, Melbourne, VIC, Australia.
    Lundh, Dan
    School of Bioscience, University of Skövde, Skövde, Sweden.
    Lorentzon, M.
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Hip fracture risk and safety with alendronate treatment in the oldest-old2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, no 6, p. 546-559Article in journal (Refereed)
    Abstract [en]

    Background. There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate's efficacy to prevent hip fractures in the oldest-old (80 years old), the population with the highest fracture risk, has not been studied.

    Objective. To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety.

    Methods. Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term.

    Results. The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49-0.79), P < 0.001) and multivariable models (HR 0.66 (0.51-0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82-0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12-2.24). The alendronate association did not change with age for hip fractures or mild UGI.

    Conclusion. In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patients.

  • 26.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Rosenquist Brandell, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Prognostic indices in chronic lymphocytic leukaemia: where do we stand how do we proceed?2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 4, p. 347-357Article, review/survey (Refereed)
    Abstract [en]

    The remarkable clinical heterogeneity in chronic lymphocytic leukaemia (CLL) has highlighted the need for prognostic and predictive algorithms that can be employed in clinical practice to assist patient management and therapy decisions. Over the last 20 years, this research field has been rewarding and many novel prognostic factors have been identified, especially at the molecular genetic level. Whilst detection of recurrent cytogenetic aberrations and determination of the immunoglobulin heavy variable gene somatic hypermutation status have an established role in outcome prediction, next-generation sequencing has recently revealed novel mutated genes with clinical relevance (e.g. NOTCH1, SF3B1 and BIRC3). Efforts have been made to combine variables into prognostic indices; however, none has been universally adopted. Although a unifying model for all groups of patients and in all situations is appealing, this may prove difficult to attain. Alternatively, focused efforts on patient subgroups in the same clinical context and at certain clinically relevant 'decision points', that is at diagnosis and at initiation of first-line or subsequent treatments, may provide a more accurate approach. In this review, we discuss the advantages and disadvantages as well as the clinical applicability of three recently proposed prognostic models, the MD Anderson nomogram, the integrated cytogenetic and mutational model and the CLL-international prognostic index. We also consider future directions taking into account novel aspects of the disease, such as the tumour microenvironment and the dynamics of (sub)clonal evolution. These aspects are particularly relevant in view of the increasing number of new targeted therapies that have recently emerged.

  • 27. 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.

  • 28. Bellavia, A
    et al.
    Larsson, S C
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fish consumption and all-cause mortality in a cohort of Swedish men and women.2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 1, p. 86-95Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epidemiological studies of fish consumption and all-cause mortality have provided inconsistent results.

    OBJECTIVE: We examined the dose-response association between fish consumption and mortality from all causes in a large population-based cohort of Swedish men and women.

    METHODS: The study included 72 522 participants (33 973 women and 38 549 men), aged 45-83 years, from the Swedish Mammography Cohort and the Cohort of Swedish Men. Information on fish consumption was obtained through a self-administered questionnaire in 1997. Participants were followed for 17 years (1 January 1998 to 31 December 2014), and data on death and causes of death were ascertained through linkage to the Swedish Cause of Death Register. We used Cox proportional hazard regression to estimate hazard ratios (HRs) of death. Fish consumption was evaluated as a continuous predictor, flexibly modelled with restricted cubic splines to assess potential nonlinear associations.

    RESULTS: During follow-up, 16 730 deaths (7168 women and 9562 men) were recorded. The dose-response association between fish consumption and all-cause mortality was U-shaped. Compared with the median fish consumption (women: 25.0; men: 30.5 g day-1 ), lower levels of consumption were progressively associated with higher mortality risk up to 25% for women [HR 1.25; 95% confidence interval (CI): 1.11, 1.40] and 19% for men (HR 1.19; 95% CI: 1.07, 1.32) with no reported consumption. Increasingly higher levels of fish consumption were associated with higher mortality risk only amongst women, with a 39% higher mortality risk amongst women reporting the highest level of fish consumption (80 g day-1 ; HR 1.39; 95% CI: 1.15, 1.68).

    CONCLUSION: These results indicate a U-shaped association between fish consumption and all-cause mortality, particularly amongst women.

  • 29.
    Bengtsson, A. A.
    et al.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Systemic lupus erythematosus: still a challenge for physicians2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 1, p. 52-64Article, review/survey (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE) has a complex clinical picture, and a number of defects in the immune system have been described in patients with the disease. Most organs can be involved in SLE, and in addition to the typical major organ manifestations (e.g. from kidneys and the central nervous system), early cardiovascular disease is a major determinant of prognosis. Several important findings during the last decade have increased the understanding of the mechanisms behind the disease characteristics and the underlying autoimmune process. Amongst, these are defects in the handling of apoptotic cells, increased expression of type I interferon-regulated genes and activation of autoreactive B cells, with both the type I interferon system and the B lymphocyte stimulator (BLyS) having key roles. In addition, a large number of genes have been identified that contribute to these abnormalities. It has also become clear that certain SLE risk genes are associated with some organ manifestations, such as STAT4 with nephritis and IRF8 with myocardial infarction. Furthermore, environmental factors that can induce SLE or trigger a disease flare have been identified. As a consequence of this increased knowledge, new treatments for SLE have been developed. The most recently approved drug for SLE is belimumab, which blocks BLyS, and several new therapies and therapeutic strategies are in the pipeline for clinical application.

  • 30. Bengtsson, A
    et al.
    Herlitz, Johan
    University of Borås, Faculty of Caring Science, Work Life and Social Welfare. [external].
    Karlsson, T
    Hjalmarson, Å
    The epidemiology of a coronary waiting list. A description of all patients1994In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, ISSN 0954-6820, Vol. 235, no 3, p. 263-269Article in journal (Refereed)
    Abstract [en]

    Keywords: cardiac symptoms; chest pain; coronary revascularization; delay; ischaemic heart disease; nervous reactions; waiting list Abstract. Objectives. To describe the characteristics and the severity of symptoms amongst patients on the waiting list for possible coronary revascularization. Design. All the patients were sent a postal questionnaire for symptom evaluation. Setting. All hospitals in western Sweden. Subjects. All patients in western Sweden on the waiting list in September 1990, who had been referred for coronary angiography or revascularization (n = 904) and a sex- and age-matched reference group (n = 809). Results. More than half of the patients had daily attacks of chest pain, whereas 16% reported less than one attack per week or no pain at all. However, other symptoms such as dyspnoea, tachycardia and nervous reactions were also common and 25% of all patients used sedatives. A long waiting time for a given procedure was not associated with more pain but with more nervous symptoms such as restlessness and insomnia (P < 0.0001) and greater use of sedatives and cigarettes (P < 0.05). Conclusions. We conclude that a long waiting time for possible coronary revascularization is associated with more nervous symptoms but not with more pain.

  • 31.
    Bengtsson, Torbjörn
    et al.
    Department of Medical and Health Sciences, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden; Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Karlsson, H
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Gunnarsson, P
    Department of Medical and Health Sciences, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Skoglund, C
    Department of Medical and Health Sciences, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Elison, C
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Leanderson, P
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Lindahl, M
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 263, no 5, p. 558-571Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Several studies support an association between periodontal disease and atherosclerosis with a crucial role for the pathogen Porphyromonas gingivalis. This study aims at investigating the proteolytic and oxidative activity of P. gingivalis on LDL in a whole blood system using a proteomic approach and analysing the effects of P. gingivalis-modified LDL on cell proliferation.

    METHODS: The cellular effects of P. gingivalis in human whole blood were assessed using lumi-aggregometry analysing reactive oxygen species production and aggregation. Blood was incubated for 30 min with P. gingivalis, whereafter LDL was isolated and a proteomic approach was applied to examine protein expression. LDL-oxidation was determined by analysing the formation of protein carbonyls. The effects of P. gingivalis-modified LDL on fibroblast proliferation were studied using the MTS assay.

    RESULTS: Incubation of whole blood with P. gingivalis caused an extensive aggregation and ROS production, indicating platelet and leucocyte activation. LDL prepared from bacteria-exposed blood showed an increased protein oxidation, elevated levels of apoM and formation of two apoB-100 N-terminal fragments. Porphyromonas gingivalis-modified LDL markedly increased the growth of fibroblasts. Inhibition of gingipain R suppressed the modification of LDL by P. gingivalis.

    CONCLUSIONS: The ability of P. gingivalis to change the protein expression and proliferative capacity of LDL may represent a crucial event in periodontitis-associated atherosclerosis.

  • 32.
    Bengtsson, Torbjörn
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Gunnarsson, Patrik
    Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Skoglund, Caroline
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Elison, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 263, no 5, p. 558-571Article in journal (Refereed)
    Abstract [en]

    Objective: Several studies support an association between periodontal disease and atherosclerosis with a crucial role for the pathogen Porphyromonas gingivalis. This study aims to investigate the proteolytic and oxidative activity of P. gingivalis on LDL in a whole blood system by using a proteomic approach and analyze the effects of P. gingivalis-modifed LDL on cell proliferation.

    Methods: The cellular effects of P. gingivalis in human whole blood were assessed using lumi-aggregometry analyzing reactive oxygen species (ROS) production and aggregation. Blood was incubated for 30 min with P. gingivalis, whereafter LDL was isolated and a proteomic approach was applied to examine protein expression. LDL-oxidation was determined by analyzing the formation of protein carbonyls. The effects of P. gingivalis-modifed LDL on fibroblast proliferation were studied using the MTS-assay.

    Results: Incubation of whole blood with P. gingivalis caused an extensive aggregation and ROS-production, indicating platelet and leukocyte activation. LDL prepared from the bacteria-exposed blood showed an increased protein oxidation, elevated levels of apoM and formation of two apoB-100 N-terminal fragments. P. gingivalis-modified LDL markedly increased the growth of fibroblasts. Inhibition of gingipain R suppressed the modification of LDL by P. gingivalis.

    Conclusions: The ability of P. gingivalis to change the protein expression and the proliferative capacity of LDL may represent a crucial event in periodontitis-associated atherosclerosis.

  • 33.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Clinical implications of omics and systems medicine: focus on predictive and individualized treatment2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 3, p. 229-240Article, review/survey (Refereed)
    Abstract [en]

    Many patients with common diseases do not respond to treatment. This is a key challenge to modern health care, which causes both suffering and enormous costs. One important reason for the lack of treatment response is that common diseases are associated with altered interactions between thousands of genes, in combinations that differ between subgroups of patients who do or do not respond to a given treatment. Such subgroups, or even distinct disease entities, have been described recently in asthma, diabetes, autoimmune diseases and cancer. High-throughput techniques (omics) allow identification and characterization of such subgroups or entities. This may have important clinical implications, such as identification of diagnostic markers for individualized medicine, as well as new therapeutic targets for patients who do not respond to existing drugs. For example, whole-genome sequencing may be applied to more accurately guide treatment of neurodevelopmental diseases, or to identify drugs specifically targeting mutated genes in cancer. A study published in 2015 showed that 28% of hepatocellular carcinomas contained mutated genes that potentially could be targeted by drugs already approved by the US Food and Drug Administration. A translational study, which is described in detail, showed how combined omics, computational, functional and clinical studies could identify and validate a novel diagnostic and therapeutic candidate gene in allergy. Another important clinical implication is the identification of potential diagnostic markers and therapeutic targets for predictive and preventative medicine. By combining computational and experimental methods, early disease regulators may be identified and potentially used to predict and treat disease before it becomes symptomatic. Systems medicine is an emerging discipline, which may contribute to such developments through combining omics with computational, functional and clinical studies. The aims of this review are to provide a brief introduction to systems medicine and discuss how it may contribute to the clinical implementation of individualized treatment, using clinically relevant examples.

  • 34. Berglin Blohm, M
    et al.
    Hartford, M
    Karlsson, T
    Herlitz, Johan
    University of Borås, Faculty of Caring Science, Work Life and Social Welfare. [external].
    Factors associated with prehospital and in-hospital delay time in acute myocardial infarction: a 6-year experience1998In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 243, no 3, p. 243-250Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To explore factors associated with delay time prior to hospital admission and in hospital amongst acute myocardial infarction (AMI) patients with particular emphasis on the delay time to the administration of thrombolytic therapy. METHODS: During a 6-year period we prospectively computerized pre-hospital and in-hospital time intervals for AMI patients admitted to the coronary care unit (CCU) direct from the emergency department (ED) or via paramedics, at Sahlgrenska Hospital, Göteborg, Sweden. RESULTS: Pre-hospital delay: independent predictors of a prolonged delay were increased age (P = 0.0007), female sex (P = 0.02) and a history of hypertension (P = 0.03). For AMI patients who received thrombolytic treatment and the only independent predictor of a prolonged delay was increased age (P = 0.005). In-hospital delay: for all AMI patients independent predictors of a prolonged delay were prolonged pre-hospital delay (P < 0.0001), increased age (P = 0.03) and a history of angina (P = 0.002), hypertension (P = 0.01) and diabetes (P = 0.01). For thrombolytic treated AMI patients independent predictors of a prolonged delay were prolonged pre-hospital delay (P < 0.0001), female sex (P = 0.02) and a history of diabetes (P = 0.02). CONCLUSION: Risk factors for both pre-hospital and hospital delay time could in AMI be defined although slightly different. Two factors appeared for both, i.e. increasing age and a history of hypertension.

  • 35. Bergström, G
    et al.
    Berglund, G
    Blomberg, A
    Brandberg, J
    Engström, G
    Engvall, J
    Eriksson, M
    de Faire, U
    Flinck, A
    Hansson, Mats G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Hedblad, B
    Hjelmgren, O
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, T
    Johnsson, Å
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Löfdahl, C-G
    Melander, O
    Östgren, C J
    Persson, A
    Persson, M
    Sandström, A
    Schmidt, C
    Söderberg, S
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Toren, K
    Waldenström, A
    Wedel, H
    Vikgren, J
    Fagerberg, B
    Rosengren, A
    The Swedish CArdioPulmonary BioImage Study: objectives and design2015In: 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.

  • 36.
    Bergström, G
    et al.
    University of Gothenburg / Sahlgrenska University Hospital.
    Berglund, G
    Lund University.
    Blomberg, A
    Umeå University.
    Brandberg, J
    Sahlgrenska University Hospital / University of Gothenburg.
    Engström, G
    Lund University.
    Engvall, Jan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Eriksson, M
    Karolinska University Hospital, Stockholm.
    de Faire, U
    Karolinska Institutet, Stockholm / Karolinska University Hospital, Stockholm.
    Flinck, A
    Sahlgrenska University Hospital, Stockholm / University of Gothenburg.
    Hansson, M G
    Uppsala University.
    Hedblad, B
    Lund University.
    Hjelmgren, O
    University of Gothenburg / Sahlgrenska University Hospital, Gothenburg.
    Janson, C
    Uppsala University.
    Jernberg, T
    Karolinska University Hospital, Stockholm / Karolinska Institutet, Stockholm.
    Johnsson, Å
    Sahlgrenska University Hospital, Gothenburg / University of Gothenburg.
    Johansson, L
    Unit of Radiology.
    Lind, L
    Uppsala University.
    Löfdahl, C-G
    Lund University / Lund University Hospital.
    Melander, O
    Lund University / Skåne University Hospital, Malmö.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Persson, M
    Lund University / Skåne University Hospital, Malmö.
    Sandström, A
    Umeå University.
    Schmidt, C
    University of Gothenburg.
    Söderberg, S
    Umeå University.
    Sundström, J
    Uppsala University / Uppsala Clinical Resarch Centre.
    Toren, K
    University of Gothenburg.
    Waldenström, A
    Umeå University Hospital.
    Wedel, H
    Nordic School of Public Health, Gothenburg.
    Vikgren, J
    Sahlgrenska University Hospital, Gothenburg / University of Gothenburg.
    Fagerberg, B
    University of Gothenburg.
    Rosengren, A
    University of Gothenburg.
    The Swedish CArdioPulmonary BioImage Study: objectives and design2015In: 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.

  • 37. 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.

  • 38. 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.

  • 39. 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.

  • 40.
    Björck, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Persson, Karin
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Rundkvist, Louise
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Hamsten, A
    Karolinska Institute.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eriksson, P
    Karolinska Institute, Stockholm.
    Association of genetic variation on chromosome 9p21.3 and arterial stiffness2009In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 265, no 3, p. 373-381Article in journal (Refereed)
    Abstract [en]

    Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases, such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analysed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals.

    A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness.

    Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.

  • 41.
    Björkegren, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Elevated serum levels of methylmalonic acid and homocysteine in elderly people: a population-based intervention study1999In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 246, no 6, p. 603-611Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    There is uncertainty amongst clinicians about the definitions of cobalamin and folate deficiency and therefore about the indications for treatment. In this report we present the results of systematic cobalamin and folic acid treatment based upon serum cobalamin, total homocysteine (tHcy) and methylmalonic acid (MMA) analyses in a population-based sample.

    SUBJECTS:

    A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey (n = 266). Sixty-nine persons who had serum cobalamin < 300 pmol L-1 and serum MMA >/=0.37 micromol L-1 or serum tHcy >/=15 micromol L-1 and who had no cobalamin or folic acid substitution were selected for treatment.

    INTERVENTIONS:

    Initially all 69 patients were given cobalamin orally or intramuscularly. Those who remained high in tHcy were in addition given folic acid treatment.

    MAIN OUTCOME MEASURES:

    Serum cobalamin, serum MMA and serum tHcy.

    RESULTS:

    After 6 months of cobalamin treatment, serum MMA became normal in 13 out of 15 persons. Mean serum tHcy decreased but was normalized in only 15 out of 56 persons. After 3 months of folic acid treatment added to those who still had an abnormal serum tHcy, serum tHcy had normalized in all but one person.

    CONCLUSIONS:

    Cobalamin treatment normalizes increased MMA values and combined cobalamin and folic acid treatment normalizes tHcy, suggesting a pretreatment deficiency of tissue cobalamin and folate in spite of normal serum cobalamin and folate values in the majority of cases.

  • 42.
    Björkegren, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Reported symptoms and clinical findings in relation to serum cobalamin, folate, methylmalonic acid and total homocysteine among elderly Swedes: a population-based study2003In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 254, no 4, p. 343-352Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    The early stages of tissue B12 or folate deficiency often cause diagnostic problems. In this report, the levels of serum cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy), and their relationships with clinical findings and reported symptoms in a representative random population sample are presented.

    DESIGN:

    Cohort study.

    SETTING:

    A general central Swedish population 70 years or older.

    SUBJECTS AND METHODS:

    A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey. A total of 235 (85%) persons responded, of whom 161 had no interfering diseases or medication. Blood specimens for serum cobalamin, folate, MMA and tHcy analyses were drawn.

    MAIN OUTCOME MEASURES:

    Presence of anaemic, gastrointestinal, neurological and psychiatric symptoms, obtained by questionnaire, and vibration sense measurement and findings at a physical and Mini Mental State Examination.

    RESULTS:

    Among a large number of symptoms and clinical findings that traditionally have been linked to vitamin B12 or folate tissue deficiency, only changes in the tongue mucosa and mouth angle stomatitis turned out to be significantly associated with abnormal serum tHcy and serum folate levels. There were no relationships to serum cobalamin and serum MMA.

    CONCLUSIONS:

    Changes in the oral mucosa were the only signs and symptoms found in this study, indicating that these may be the very early markers of metabolic defects. The traditional symptoms of vitamin deficiency may appear later in the course.

  • 43.
    Björkegren, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Serum cobalamin, folate, methylmalonic acid and total homocysteine as vitamin B12 and folate tissue deficiency markers amongst elderly Swedes: a population-based study2001In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 249, no 5, p. 423-32Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES

    The possibilities of detecting tissue cobalamin and folate deficiency are under debate. In this report the levels of serum cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy) and their interrelations in a representative random population sample are presented.

    DESIGN

    Cohort study.

    SETTING

    A general mid-Swedish population.

    SUBJECTS

    A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey. A total of 235 (85%) persons responded, out of whom 224 had no interfering diseases.

    MAIN OUTCOME MEASURES

    Serum cobalamin, folate, MMA and tHcy.

    RESULTS

    The serum levels of cobalamin, folate, MMA and tHcy were all correlated to cobalamin and folic acid treatment. They were also correlated to the intake of multivitamin preparations. In addition, serum cobalamin was higher in untreated women than in men but not correlated to age. Serum folate was correlated neither to sex nor age. Serum tHcy and MMA were both directly correlated to age but MMA not to sex. MMA was inversely correlated to serum cobalamin but not to serum folate, whereas serum tHcy was inversely correlated to serum cobalamin, folate and creatinine. Neither serum cobalamin, folate, MMA nor tHcy had any significant correlation to haemoglobin, erythrocyte volume fraction (EVF) or mean red cell volume. Half of the study population had abnormal MMA or tHcy levels, suggesting a latent or overt tissue deficiency of cobalamin or folate.

    CONCLUSIONS

    A substantial proportion of the elderly general population had signs of low tissue levels of cobalamin or folate. Amongst those who took multivitamin preparations this proportion was much lower.

  • 44.
    Björklund, Peyman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Pacak, K.
    NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol Program Reprod & Adult E, Bethesda, MD USA..
    Crona, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Precision medicine in pheochromocytoma and paraganglioma: current and future concepts2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 6, p. 559-573Article in journal (Refereed)
    Abstract [en]

    Pheochromocytoma and paraganglioma (PPGL) are rare diseases but are also amongst the most characterized tumour types. Hence, patients with PPGL have greatly benefited from precision medicine for more than two decades. According to current molecular biology and genetics-based taxonomy, PPGL can be divided into three different clusters characterized by: Krebs cycle reprogramming with oncometabolite accumulation or depletion (group 1a); activation of the (pseudo)hypoxia signalling pathway with increased tumour cell proliferation, invasiveness and migration (group 1b); and aberrant kinase signalling causing a pro-mitogenic and anti-apoptotic state (group 2). Categorization into these clusters is highly dependent on mutation subtypes. At least 12 different syndromes with distinct genetic causes, phenotypes and outcomes have been described. Genetic screening tests have a documented benefit, as different PPGL syndromes require specific approaches for optimal diagnosis and localization of various syndrome-related tumours. Genotype-tailored treatment options, follow-up and preventive care are being investigated. Future new developments in precision medicine for PPGL will mainly focus on further identification of driver mechanisms behind both disease initiation and malignant progression. Identification of novel druggable targets and prospective validation of treatment options are eagerly awaited. To achieve these goals, we predict that collaborative large-scale studies will be needed: Pheochromocytoma may provide an example for developing precision medicine in orphan diseases that could ultimately aid in similar efforts for other rare conditions.

  • 45. Björnsdottir, Sigridur
    et al.
    Sääf, Maria
    Bensing, Sophie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ludvigsson, Jonas F
    Risk of Hip Fracture in Addison's Disease: A Population-based Cohort Study2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 2, p. 187-195Article in journal (Refereed)
    Abstract [en]

    Objectives:  The results of studies of bone mineral density (BMD) in Addison's disease (AD) are inconsistent. There are no published data on hip fracture risk in patients with AD. In this study we compare hip fracture risk in adults with and without AD. Design:  A population-based cohort study. Methods:  Through the Swedish National Patient Register and the Total Population Register, we identified 3,219 patients without prior hip fracture who were diagnosed with AD at the age of ≥30 years during the period 1964-2006, and 31,557 age- and sex-matched controls. Time to hip fracture was measured. Results:  We observed 221 hip fractures (6.9%) in patients with AD and 846 (2.7%) in the controls. Patients with AD had a higher risk of hip fracture (hazard ratio (HR) = 1.8; 95% confidence interval (CI), 1.6-2.1; p < 0.001). This risk increase was independent of sex and age at or calendar period of diagnosis. Risk estimates did not change with adjustment for type 1 diabetes, autoimmune thyroid disease, rheumatoid arthritis or coeliac disease. Women diagnosed with AD ≤50 years old had the highest risk of hip fracture (HR = 2.7; 95% CI, 1.6-4.5). We found a positive association between hip fracture and undiagnosed AD (odds ratio (OR) = 2.4; 95% CI, 2.1- 3.0) with the highest risk estimates in the last year before AD diagnosis (OR = 2.8; 95% CI, 1.8-4.2). Conclusion:  Both clinically undiagnosed and diagnosed AD were associated with hip fractures, with the highest relative risk seen in women diagnosed with AD ≤50 years of age.

  • 46.
    Blokzijl, Andries
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular tools.
    Friedman, Mikaela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular tools.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular tools.
    Profiling protein expression and interactions: proximity ligation as a tool for personalized medicine2010In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 268, no 3, p. 232-245Article, review/survey (Refereed)
    Abstract [en]

    Blokzijl A, Friedman M, Ponten F, Landegren U (From the Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden). Profiling protein expression and interactions: proximity ligation as a tool for personalized medicine. (Review) J Intern Med 2010; 268: 232-245. The ability to detect very low levels of expressed proteins has enormous potential for early diagnostics and intervention at curable stages of disease. An extended range of targets such as interacting or post-translationally modified proteins can further improve the potential for diagnostics and patient stratification, and for monitoring response to treatment. These are critical building blocks for personalized treatment strategies to manage disease. The past few decades have seen a remarkably improved understanding of the molecular basis of disease in general, and of tumour formation and progression in particular. This accumulated knowledge creates opportunities to develop drugs that specifically target molecules or molecular complexes critical for survival and expansion of tumour cells. However, tumours are highly variable between patients, necessitating the development of diagnostic tools to individualize treatment through parallel analysis of sets of biomarkers. The proximity ligation assay (PLA) can address many of the requirements for advanced molecular analysis. The method builds on the principle that recognition of target proteins by two, three or more antibodies can bring in proximity DNA strands attached to the antibodies. The DNA strands can then participate in ligation reactions, giving rise to molecules that are amplified for highly sensitive detection. PLA is particularly well suited for sensitive, specific and multiplexed analysis of protein expression, post-translational modifications and protein-protein interactions. The analysis of this extended range of biomarkers will prove critical for the development and implementation of personalized medicine.

  • 47.
    Blom, Hans
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    STED microscopy: increased resolution for medical research?2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 276, no 6, p. 560-578Article, review/survey (Refereed)
    Abstract [en]

    Optical imaging is crucial for addressing fundamental problems in all areas of life science. With the use of confocal and two-photon fluorescence microscopy, complex dynamic structures and functions in a plethora of tissue and cell types have been visualized. However, the resolution of classical' optical imaging methods is poor due to the diffraction limit and does not allow resolution of the cellular microcosmos. On the other hand, the novel stimulated emission depletion (STED) microscopy technique, because of its targeted on/off-switching of fluorescence, is not hampered by a diffraction-limited resolution barrier. STED microscopy can therefore provide much sharper images, permitting nanoscale visualization by sequential imaging of individual-labelled biomolecules, which should allow previous findings to be reinvestigated and provide novel information. The aim of this review is to highlight promising developments in and applications of STED microscopy and their impact on unresolved issues in biomedical science.

  • 48.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Atrial fibrillation: from atrial extrasystoles to atrial cardiomyopathy - what have we learned from basic science and interventional procedures?2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 5, p. 406-411Article in journal (Other academic)
  • 49.
    Boden, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Molin, E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Jernberg, T.
    Kieler, H.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Higher mortality after myocardial infarction in patients with severe mental illness: a nationwide cohort study2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 6, p. 727-736Article in journal (Refereed)
    Abstract [en]

    ObjectivesThe aim of this study was to explore the impact of severe mental illness (SMI) on myocardial infarction survival and determine the influence of risk factor burden, myocardial infarction severity and different treatments. Design, setting and participantsThis population-based cohort study, conducted in Sweden during the period 1997-2010, included all patients with a first diagnosis of myocardial infarction in the Swedish nationwide myocardial infarction register SWEDEHEART (n=209592). Exposure was defined as a diagnosis of SMI (i.e. bipolar disorder or schizophrenia) in the national patient register prior to infarction. Bias-minimized logistic regression models were identified using directed acyclic graphs and included covariates age, gender, smoking, diabetes, previous cardiovascular disease, myocardial infarction characteristics and treatment. Main outcome measuresThe outcomes were 30-day and 1-year mortality, obtained through linkage with national population registers. ResultsPatients with bipolar disorder (n=442) and schizophrenia (n=541) were younger (mean age 68 and 63years, respectively) than those without SMI (n=208609; mean age 71years). The overall 30-day and 1-year mortality rates were 10% and 18%, respectively. Compared with patients without SMI, patients with SMI had higher 30-day [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.55-2.56] and 1-year mortality (OR 2.11, 95% CI 1.74-2.56) in the fully adjusted model. The highest mortality was observed amongst patients with schizophrenia (30-day mortality: OR 2.58, 95% CI 1.88-3.54; 1-year mortality: OR 2.55, 95% CI 1.98-3.29). ConclusionSMI is associated with a markedly higher mortality after myocardial infarction, also after accounting for contributing factors. It is imperative to identify the reasons for this higher mortality.

  • 50. Brauner, S.
    et al.
    Zhou, W.
    Backlin, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Green, T. M.
    Folkersen, L.
    Ivanchenko, M.
    Lofstrom, B.
    Xu-Monette, Z. Y.
    Young, K. H.
    Pedersen, L. Moller
    Moller, M. Boe
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Enblad, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Wahren-Herlenius, M.
    Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, no 3, p. 323-332Article in journal (Refereed)
    Abstract [en]

    ObjectiveTRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21 in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. Materials and methodsTRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR and correlated with H-3-thymidine incorporation and propidium iodine staining. ResultsTRIM21 expression levels differed in the lymphomas compared to normal lymphoid tissue, with reduced expression correlating with shorter overall survival in all three cohorts. In the two larger cohorts, progression-free survival was assessed and was also found to correlate with TRIM21 expression. The association was independent of commonly used clinical prognostic scores, lymphoma subtype and several previously reported prognostic biomarkers. In agreement with this clinical observation, we noted an inverse correlation between TRIM21 expression and proliferation of leucocytes invitro. ConclusionsWe show that loss of TRIM21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM21 expression is associated with better prognosis in patients with DLBCL. Based on our findings, we suggest that TRIM21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival.

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