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  • 51.
    El-Salhy, Magdy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Effects of octreotide, galanin and serotonin on a human gastric cancer cell line.2005In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 13, no 5, p. 787-791Article in journal (Refereed)
    Abstract [en]

    Human gastric cancer cell line was exposed in vitro to octreotide, galanin and serotonin alone, or in double or triple combination, and the number of viable cells and proliferation index were measured after 3, 6 and 12 h. The tumour cells were also implanted subcutaneously in nude mice. After 8 days, the animals were randomly allocated to either of two groups, with 8 in each. The first group received a bolus intraperitoneal injection, twice daily with 100 microl sterile saline solution for 10 days, while the second group was given sterile saline solution containing 100 microg/kg body weight of octreotide, galanin and serotonin. In vitro exposure to octreotide, galanin and serotonin alone or in double or triple combination reduced the number of viable cells and proliferation index. Both the volume and weight of tumours in mice given triple therapy were less than in controls. There was no statistical difference between treated and control tumours regarding proliferation and apoptotic indices or the labelling index of epidermal growth factor (EGF). It was concluded that the reduction in tumour volume and weight following triple treatment in vivo experiments could be not explained by inhibition of proliferation, induction of apoptosis or decreased expression of EGF of the tumour cells, and that other mechanisms must be involved. The reduction of proliferation in vitro but not in vivo could not be explained by the difference in concentrations of octreotide, galanin and serotonin used in vitro and in vivo.

  • 52.
    El-Salhy, Magdy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Effects of triple therapy with octreotide, galanin and serotonin on a human colon cancer cell line.2005In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 13, no 1, p. 45-49Article in journal (Refereed)
    Abstract [en]

    Human colon cancer cells were implanted subcutaneously into nude mice. After 12 days, the animals were divided into two groups. The first group received 40 microg/kg body weight of octreotide, galanin and serotonin via an intraperitoneally implanted pump. The second group received sterile saline only. Treatment lasted for 14 days. The volume and weight of the tumours in treated mice tended to decrease, though not with statistical significance. The proliferation index and the number of tumour blood vessels was significantly reduced in the mice given triple therapy. The apoptotic index, as detected by TUNEL method and monoclonal anti-poly (ADP-ribose) polymerase, was significantly higher in the treated mice. Though the results of this investigation are promising, it is uncertain as to what use the present findings may imply for the treatment of patients with colorectal cancer.

  • 53.
    El-Salhy, Magdy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Effects of triple therapy with octreotide, galanin and serotonin on a human colon cancer cell line implanted in mice: Comparison between different routes of administration2005In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 20, no 1, p. 19-25Article in journal (Refereed)
    Abstract [en]

    A human colon cancer cell line was implanted subcutaneously in nude mice. After 7 days, the animals were divided into four groups. The first group received an intraperitoneal (i.p.) continuous infusion by an osmotic pump, the second was given i.p. bolus injections, the third received continuous subcutaneous (s.c.) infusion by an osmotic pump and the fourth group was given bolus s.c. injections. Each group was divided into 2 subgroups. The first subgroup received triple treatment with octreotide, galanin, and serotonin, 40 μg/kg body weight/day of each. The second subgroup was given sterile saline solution. Treatment lasted for 14 days. The volume and wet weight of the tumours in all treated groups tended to decrease, but was statistically significant only in the group with continuous i.p. infusion. The number of viable cells tended to decrease in all the treated groups, but was not statistically significant. Proliferation index was significantly reduced in mice given triple therapy i.p. as bolus injection and as continuous infusion, as compared with their respective controls. The apoptotic index increased significantly in mice receiving triple therapy as continuous i.p. infusion as revealed by both the TUNEL method and by poly (ADP-ribose) polymerase (PARP) expression. The number of tumour blood vessels was significantly reduced in the mice given triple therapy as continuous i.p. infusion, as compared with controls. There was no statistical difference between animals treated by different routes, regarding proliferation or apoptosis of the cancer cells, or the number or mean luminal area of tumour blood vessels. The present investigation showed that regardless of the route of administration, triple therapy with octreotide, galanin and serotonin generally reduced the volumes, weights, viable cells, vascularization and proliferation of the tumours, as well as inducing apoptosis. Continuous i.p. infusion appears, however, to be the most effective route of administration.

  • 54.
    El-Salhy, Magdy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Neuroendocrine Immune Network in Ageing2004Book (Other academic)
    Abstract [en]

    The book describes the mechanisms involved in the maintenance of neuroendocrine-immune interactions in ageing. The lack of this maintenance leads to the appearance of age-related diseases (cancer, infections, dementia) and subsequent disability. The capacity of some hormones or nutritional factors in restoring and remodelling the neuroendocrine-immune response during ageing is reported presenting possible new anti-ageing strategies in order to reach healthy ageing and longevity.

  • 55.
    El-Salhy, Magdy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Triple treatment with octreotide, galanin and serotonin is a promising therapy for colorectal cancer2005In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 11, no 16, p. 2107-2117Article in journal (Refereed)
    Abstract [en]

    In patients with colorectal cancer, low levels of colonic somatostatin, galanin and serotonin have been found. Based on these findings, the effects of triple treatment with octreotide (a somatostatin analogue), galanin and serotonin on colorectal cancer has been studied. Triple therapy was found to reduce the volume and weight of both rat and human colon carcinoma in xenografts, apparently by necrosis, but also by reducing proliferation and expression of epidermal growth factor of cancer cells, and also by inducing apoptosis. It has been suggested that tumour necrosis results from ischemia in the tumour caused by a reduction in the tumour blood flow, a consequence of reduced number of tumour-feeding blood vessels and by constricting of tumour feeding arterioles. The effects of treating rat colorectal cancer using single, double and triple therapy with octreotide, galanin and serotonin were studied. Of these substances, galanin alone achieved a significant reduction in tumour-feeding blood vessels. Single and double regimes had some effect, but were not nearly so successful as triple treatment. The optimum treatment dose of triple therapy lies between 40 and 80 μg/kg/day, smaller doses had no effect on the tumours at all, while larger doses had no additional effect. The optimal administration route is continuous i.p. infusion, for 14 days. Triple therapy gave no obvious side effects, and had equivalent anti-tumour and therapeutic efficacy as standard treatment with 5-fluorouracil/leucovorin. Although this treatment appears to be a promising option, clinical trials need be conducted to establish whether it can be beneficial in clinical use. © 2005 Bentham Science Publishers Ltd.

  • 56.
    El-Salhy, Magdy
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Dennerqvist, Veronica
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Effects of triple therapy with octreotide, galanin and serotonin on liver metastasis of human colon cancer in xenografts.2004In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 11, no 6, p. 1177-1182Article in journal (Refereed)
    Abstract [en]

    Human colon cancer cells (SW 620) were implanted under the capsule of the left liver lobe of female nude (C57BL/6JBom-nu) mice. After 7 days, relaparatomy was performed and an ALZET osmotic pump was implanted intraperitoneally and left in situ for 14 days. The mice were divided into 2 groups, 10 in each. The first group received 40 micro g/kg body weight of octreotide, galanin and serotonin, and the second group received sterile saline. The number of metastases in the liver, and to the intra-abdominal lymph nodes was significantly greater in the controls. The incidence of metastases to the peritoneal cavity was lower in the treated animals (though not statistically significantly). Tumour volume, wet weight, proliferation index and number of tumour blood vessels decreased significantly in the treated animals. The apoptotic index was significantly higher in the treated mice. The decrease in the volume and weight of tumours following the triple therapy seemed to be caused by low proliferation, and increased apoptosis, and reduced vascularization of the tumours. The low invasion of cancer cells observed following this treatment could have been due to the low tumour burden, and to the reduced number of the blood and lymph vessels.

  • 57.
    El-Salhy, Magdy
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hilding, L
    Royson, H
    Tjomsland, Veronica
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Comparison between triple therapy with octreotide, galanin and serotonin vs. irinotecan or oxaliplatin in combination with 5-fluorouracil/leukovorin in human colon cancer.2005In: International Journal of Oncology, ISSN 1019-6439, Vol. 27, no 3, p. 687-691Article in journal (Refereed)
    Abstract [en]

    Human colon cancer cells were injected sub-cutaneously into 30 nude mice. After 8 days, the animals were divided into 3 equal groups. The first and second groups received an i.p. injection with 5-fluorouracil/leukovorin (5-FU/LV) for 5 days (20 mg and 10 mg/kg body weight respectively). On the first day of 5-FU/LV treatment, the first group received an i.p. injection of irinotecan (2.5 mg/kg body weight), and the second group received an i.p. injection with oxaliplatin (1 mg/kg body weight). The third group were injected i.p. with 100 microl saline solution containing octreotide, galanin and serotonin. Injections were given 3 times daily for 5 days with a total dose of 150 microg/kg body weight/day. Three days after the treatment, the animals were sacrificed. Whereas the animals treated with triple therapy held a stable body weight, animals treated with 5-FU/LV-irinotecan and 5-FU/LV-oxaliplatin had gradual weight loss, which amounted to approximately 25% of their body weight at the end of the experiment. Moreover, 2 mice in the group treated with 5-FU/LV-irinotecan died, most probably due to side effects. There was no statistically significant difference between the 3 groups regarding tumour proliferation, apoptosis, blood vessel density, EGF- and VEGF-expression. Treatment with triple therapy using octreotide, galanin and serotonin appear to be comparable to 5-FU/LV in combination with irinotecan and oxaliplatin. However, triple therapy seems to have a better safety profile.

  • 58.
    El-Salhy, Magdy
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tjomsland, Vegard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Effects of triple treatment with octreotide, galanin and serotonin on a human pancreas cancer cell line in xenografts2005In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 20, no 3, p. 745-752Article in journal (Refereed)
    Abstract [en]

    Human pancreas cancer cells were implanted s.c. in nude mice. After 11 days, the mice were divided into two groups of 13. The first group received sterile saline solution and the second received triple therapy containing octreotide, galanin and serotonin, 40 μg/kg/day as a continuous i.p. infusion via an implanted osmotic pump for 14 days. Triple therapy prolonged the survival rate of the mice bearing human pancreatic carcinoma. Both the volume and weight of tumours in mice given triple therapy were less than in controls (not statistically significant). The proliferation index and the labelling index for epidermal growth factor (EGF) increased significantly in mice given triple therapy vis-á-vis controls. There was no statistically significant difference between control and treated tumours as regards, apoptotic index, necrosis, or number of tumour blood vessels. The increased survival rate was attributed to the reduced tumour load, since both weight and volume were reduced. It is most probable that octreotide was the responsible agent. Further investigation with single and double combinations of octreotide, galanin and serotonin are needed to identify the cause of increased cell proliferation in tumours subjected to these bioactive substances. Identifying the agent(s) inducing pancreatic cancer cell proliferation may be useful in combining a new treatment, as antagonists to these bioactive substances are available.

  • 59.
    Ericson, Ann-Charlott
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Nur, E Mohammed
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Petersson, F
    Karolinska University Hospital.
    Kechagias, Stergios
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    The Effects of Capsaicin on Gastrin Secretion in Isolated Human Antral Glands: Before and After Ingestion of Red Chilli2009In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 54, no 3, p. 491-498Article in journal (Refereed)
    Abstract [en]

    Background: Capsaicin is known to have regulatory effects on gastrointestinal functions via the vanilloid receptor (VR1). We reported previously that endocrine-like cells in the human antrum express VR1.

    Aim: To identify VR1-expressing endocrine-like cells in human antral glands and to examine whether stimulation with capsaicin causes release of gastrin, somatostatin, and serotonin. Further, to investigate the effects of a chilli-rich diet.

    Methods: Gastroscopic biopsies were received from 11 volunteers. Seven of the 11 subjects agreed to donor gastric biopsies a second time after a 3-week chilli-rich diet containing 1.4-4.2 mg capsaicin/day. VR1-immunoreactive cells were identified by double-staining immunohistochemistry against gastrin, somatostatin, and serotonin. For the stimulation studies, we used an in vitro method where antral glands in suspension were stimulated with 0.01 mM capsaicin and physiological buffer was added to the control vials. The concentrations of secreted hormones were detected and calculated with radioimmunoassay (RIA).

    Results: The light microscopic examination revealed that VR1 was localized in gastrin cells. The secretory studies showed an increase in release of gastrin and somatostatin compared to the control vials (P = 0.003; P = 0.013). Capsaicin-stimulation caused a consistent raise of the gastrin concentrations in the gland preparations from all subjects. A chilli-rich diet had an inhibitory effect on gastrin release upon stimulation compared to the results that were obtained before the start of the diet.

    Conclusion: This study shows that capsaicin stimulates gastrin secretion from isolated human antral glands, and that a chilli-rich diet decreases this secretion.

  • 60.
    Erlingsson, Styrbjörn
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Herard, Sebastian
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    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.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Men develop more intraabdominal obesity and signs of the metabolic syndrome after hyperalimentation than women2009In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 58, no 7, p. 995-1001Article in journal (Refereed)
    Abstract [en]

    We prospectively studied the effects of fast food-based hyperalimentation on insulin sensitivity and components of the metabolic syndrome and analyzed this with respect to sex. Twelve nonobese men and 6 nonobese women (26 +/- 6.6 years old), and an age-matched control group were recruited. Subjects in the intervention group aimed for 5% to 15% weight increase by doubling their regular caloric intake based on at least 2 fast food meals a day while also adopting a sedentary lifestyle for 4 weeks (andlt;5000 steps a day). Weight of Subjects in the intervention group increased from 67.6 +/- 9.1 to 74.0 +/- 11 kg (P andlt;.001), with no sex difference with regard to this or with respect to changes of total abdominal fat volumes or waist circumferences. Fasting insulin (men: before, 3.8 +/- 1.7 mu U/mL, after, 7.4 +/- 3.1 mu U/mL; P=.004; women: before, 4.9 +/- 2.3 mu U/mL; after, 5.9 +/- 2.8 mu U/mL; P =.17), systolic blood pressure (men: before, 117 +/- 13 mm Hg; after, 127 +/- 9.1 mm Hg; P =.002; women: before, 102 +/- 5.1 mm Hg; after, 98 +/- 5.4 mm Hg; P =.39), serum low-density lipoprotein cholesterol, and apolipoprotein B increased only in the men of the intervention group. The sex differences in the metabolic responses to the intervention were linked to a considerable difference in the fat accumulation pattern; 41.4% +/- 9.2% of the increase of the fat volume in the abdominal region was accumulated intraabdominally in men and 22.7 +/- 6.5% in women (P andlt;.0001). This Study thus showed that women are protected, compared with men, against developing intraabdominal obesity when adopting a standardized obesity-provoking lifestyle. Our findings suggest that it is not different lifestyles and/or behaviors that underlie the fact that men have a higher cardiovascular risk at the same level of percentage of body fat than women.

  • 61.
    Ernersson, Åsa
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Hollman Frisman, Gunilla
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Sepa Frostell, Anneli
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    An obesity provoking behaviour negatively influences young normal weight subjects' Health Related Quality of Life and causes depressive symptoms2010In: Eating Behaviors, ISSN 1471-0153, E-ISSN 1873-7358, Vol. 11, no 4, p. 247-252Article in journal (Refereed)
    Abstract [en]

    In many parts of the world the prevalence of a sedentary lifestyle in combination with high consumption of food has increased, which contributes to increased risk for becoming overweight. Our primary aim was, in an intervention, to examine the influence on health related quality of life (HRQoL) and mood in young normal weight subjects of both sexes, when adopting an obesity provoking behaviour by increasing the energy intake via fast food and simultaneously adopting a sedentary lifestyle. A secondary aim was to follow-up possible long-term effects on HRQoL and mood 6 and 12 months after this short-term intervention.

    In this prospective study, 18 healthy normal weight subjects (mean age 26 ± 6.6 years), mainly university students were prescribed doubled energy intake, and maximum 5000 steps/day, during 4 weeks. An age and sex matched control group (n = 18), who were asked to have unchanged eating habits and physical activity, was recruited. Before and after the intervention questionnaires including Short Form-36, Hospital Anxiety Depression scale, Center of Epidemiological Studies Depression scale, Sense of Coherence and Mastery scale were completed by the subjects in the intervention group and by the controls with 4 weeks interval. Six and 12 months after the intervention the subjects underwent the same procedure as at baseline and the controls completed the same questionnaires.

    During the intervention, subjects in the intervention group increased their bodyweight and developed markedly lower physical and mental health scores on Short Form-36 as well as depressive symptoms while no changes appeared in the controls. The increase of depressive symptoms was associated with increases of energy intake, body weight and body fat. When followed up, 6 and 12 months after the intervention, physical and mental health had returned completely to baseline values, despite somewhat increased body weight.

    In conclusion, adopting obesity provoking behaviour for 4 weeks decreases HRQoL and mood in young normal weight subjects. The effect is temporary and when followed up 6 and 12 months after the short-term intervention no remaining influence is found.

  • 62.
    Ernersson, Åsa
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hollman Frisman, Gunilla
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Young healthy individuals develop lack of energy when adopting an obesity provoking behaviour for 4 weeks: a phenomenological analysis2010In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 24, no 3, p. 565-571Article in journal (Refereed)
    Abstract [en]

    During the past 20 years, a sedentary lifestyle has become more common and simultaneously the consumption of energy-dense food has increased. These are two major risk factors associated with the increase of overweight and obesity, which is found in all ages over the world. The low well-being reported by obese individuals could be associated with increased food intake or it might be a specific consequence of obesity and lack of physical fitness. The aim of this study was to describe the experience of the phenomenon, adopting an obesity provoking behaviour, by increasing energy intake and simultaneously having a sedentary lifestyle for 4 weeks in healthy, normal-weight individuals of both genders. Eighteen healthy individuals (12 men and 6 women; median age 23, range 21-44 years) were included in an intervention, with a doubled energy intake and a maximum physical activity of 5000 steps per day during 4 weeks. After completing this intervention the participants were interviewed and asked to describe their experience during the past 4 weeks. A phenomenological approach was used to gain understanding of the phenomenon and analyses of the transcripts were performed in four steps according to Giorgis method. The main essence of the phenomenon, adopting an obesity provoking behaviour, was found to be lack of energy, related to emotional life, relations and life habits. Lack of energy emerged from five structures: influenced self-confidence, commitment to oneself and others, managing eating, feelings of tiredness and physical impact. These five structures were manifested through 12 constituents. These lifestyle changes decreased the sense of well-being in nonobese healthy individuals of both genders.

  • 63.
    Ernersson, Åsa
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Long-term increase of fat mass after a four week intervention with fast food based hyper-alimentation and limitation of physical activity2010In: Nutrition & Metabolism, ISSN 1743-7075, Vol. 7, no 68Article in journal (Refereed)
    Abstract [en]

    Background: A sedentary lifestyle and increased consumption of energy dense food have become more common in many parts of the world. The aim of this study was to study long term effects on body composition after a four week intervention with fast food based hyper-alimentation and limited physical activity in young normal weight subjects.

    Method: Eighteen subjects, mean age 26 (6.6) years, increased their energy intake with in average 70% and physical activity were not to exceed 5000 steps/day. Body composition was measured by Dual energy x-ray (DXA) at baseline, after the intervention and after 12 months. A matched control group was also included. ANOVA and Student's paired and unpaired t-test were used.

    Result: During the intervention body weight increased with 6.4 (2.8) kg and DXA measurements showed increases of both fat free mass and fat mass. Six months after the intervention the subjects had lost most of the weight gain, - 4.7 (3.1) kg. Twelve months after the intervention body weight had increased with 1.5 (2.4) kg compared to baseline (p = 0.018). DXA measurements at 12 months showed unchanged fat free mass compared to baseline but higher fat mass, + 1.4 (1.9) kg (p = 0.01). After 2.5 years the increase of body weight was 3.1 (4.0) kg (p = 0.01) while there was no change in controls compared to baseline, + 0.1(2.5) kg (p = 0.88).

    Conclusion: One year after a short term intervention with increased fast food based hyper-alimentation there was an increase of fat mass but unchanged fat free mass. As the change of fat mass was larger than expected from prospective epidemiological studies and as there was no increase of body weight in controls it raises the issue whether there is a long-term effect to increase fat mass of a short period of hyper-alimentation.

  • 64.
    Faergeman, Ole
    et al.
    Arhus University Hospital.
    Holme, Ingar
    Ullevaal University Hospital.
    Fayyad, Rana
    Pfizer Inc.
    Bhatia, Sonal
    Pfizer Inc.
    Grundy, Scott M
    University of Texas.
    Kastelein, John J P
    University of Amsterdam.
    LaRosa, John C
    SUNY Hlth Science Centre.
    Lytken Larsen, Mogens
    Arhus University Hospital.
    Lindahl, Christina
    Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Olsson, Anders G
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tikkanen, Matti J
    University of Helsinki.
    Waters, David D
    San Francisco General Hospital.
    Pedersen, Terje R
    Ullevaal University Hospital.
    Plasma Triglycerides and Cardiovascular Events in the Treating to New Targets and Incremental Decrease in End-Points Through Aggressive Lipid Lowering Trials of Statins in Patients With Coronary Artery Disease2009In: AMERICAN JOURNAL OF CARDIOLOGY, ISSN 0002-9149, Vol. 104, no 4, p. 459-463Article in journal (Refereed)
    Abstract [en]

    We determined the ability of in-trial measurements of triglycerides (TGs) to predict new cardiovascular events (CVEs) using data from the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) and Treating to New Targets (TNT) trials. The trials compared atorvastatin 80 mg/day with moderate-dose statin therapy (simvastatin 20 to 40 mg/day in IDEAL and atorvastatin 10 mg/day in TNT) in patients with clinically evident coronary heart disease or a history of myocardial infarction. The outcome measurement in the present research was CVE occurring after the first year of the trial. After adjusting for age, gender, and study, risk of CVEs increased with increasing TGs (p andlt;0.001 for trend across quintiles of TGs). Patients in the highest quintile had a 63% higher rate of CVEs than patients in the lowest quintile (hazard ratio 1.63, 95% confidence interval 1.46 to 1.81) and the relation of TGs to risk was apparent even within the normal range of TGs. The ability of TG measurements to predict risk decreased when high-density lipoprotein cholesterol and apolipoprotein B:apolipoprotein A-I were included in the statistical analysis, and it was abolished with inclusion of further variables (diabetes, body mass index, glucose, hypertension, and smoking; (p = 0.044 and 0.621, respectively, for trend across quintiles of TGs). Similar results were obtained in patients in whom low-density lipoprotein cholesterol had been lowered to guideline-recommended levels. In conclusion, even slightly increased TG levels are associated with higher risk of recurrence of CVEs in statin-treated patients and should be considered a useful marker of risk.

  • 65. Fellstrom, B
    et al.
    Holdaas, H
    Jardine, AG
    Holme, I
    Nyberg, G
    Fauchald, P
    Gronhagen-Riska, C
    Madsen, S
    Neumayer, HH
    Cole, E
    Maes, B
    Ambuhl, P
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hartmann, A
    Logan, JO
    Pedersen, TR
    Effect of fluvastatin on renal end points in the Assessment of Lescol in Renal Transplant (ALERT) trial2004In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 66, no 4, p. 1549-1555Article in journal (Refereed)
    Abstract [en]

    Background. Hyperlipidemia is a risk factor for long-term renal transplant dysfunction, but no prospective clinical trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effect of fluvastatin on long-term renal transplant function and development of chronic allograft nephropathy in the ALERT (Assessment of Lescol in Renal Transplantation) study. Methods. ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 mg and 80 mg daily, in renal transplant recipients. Patients were randomized to receive either fluvastatin (N = 1050) or placebo (N = 1052) and followed for five to six years. Renal end points included graft loss or doubling of serum creatinine or death, glomerular filtration rate (GFR) was also measured during follow-up in a subset of patients (N = 439). Results. There were 283 patients (13.5%) with graft loss, mainly due to chronic rejection (82%), yielding an annual rate of 2.4%. Fluvastatin treatment significantly lowered mean low-density lipoprotein (LDL)-cholesterol levels by 32% (95% CI 33 to 30) compared with placebo, but had no significant effect on the incidence of renal graft loss or doubling of serum creatinine, or decline in GFR throughout follow-up in the whole study population. Neither was any treatment effect by fluvastatin found in any of the subgroups analyzed. Conclusion. Fluvastatin treatment significantly improves lipid values in renal transplant recipients but has no effect on graft loss or doubling of serum creatinine.

  • 66.
    Fellstrom, B.
    et al.
    Fellström, B., University Hospital, Uppsala, Sweden, Department of Medical Science, Renal Unit, University Hospital, Uppsala, Sweden.
    Holdaas, H.
    Rikshospitalet, Oslo, Norway.
    Jardine, A.G.
    University of Glasgow, Glasgow, United Kingdom.
    Nyberg, G.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Gronhagen-Riska, C.
    Grönhagen-Riska, C., University Hospital, Helsinki, Finland.
    Madsen, S.
    Skejby Hospital, Aarhus, Denmark.
    Neumayer, H.-H.
    Univ. Klin. Charité, Berlin, Germany.
    Cole, E.
    Toronto General Hospital, Toronto, Ont., Canada.
    Maes, B.
    University Hospital, Leuven, Belgium.
    Ambuhl, P.
    Ambühl, P., University Hospital, Zürich, Switzerland.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Staffler, B.
    Novartis, Basel, Switzerland.
    Pedersen, T.R.
    Preventive Medicine Clinic, Ullevaal University Hospital, Oslo, Norway.
    Risk factors for reaching renal endpoints in the Assessment of Lescol in Renal Transplantation (ALERT) trial2005In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 79, no 2, p. 205-212Article in journal (Refereed)
    Abstract [en]

    Background. The aim of the study was to identity risk factors for long-term renal transplant function and development of chronic allograft nephropathy (CAN) in renal transplant recipients included in the Assessment of Lescol in Renal Transplantation (ALERT) trial. Methods. The ALERT trial was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 and 80 mg/day, in renal transplant recipients who were randomized to receive fluvastatin (Lescol) (n=1,050) or placebo (n=1,052) over 5 to 6 years of follow-up. Renal endpoints including graft loss or doubling of serum creatinine or death were analyzed by univariate and multivariate regression analysis in the placebo group. Results. There were 137 graft losses (13.5%) in the placebo group, mainly caused by CAN (82%). Univariate risk factors for graft loss or doubling of serum creatinine were as follows: serum creatinine, proteinuria, hypertension, pulse pressure, time since transplantation, donor age, human leukocyte antigen-DR mismatches, treatment for rejection, low high-density lipoprotein cholesterol, and smoking. Multivariate analysis revealed independent risk factors for graft loss as follows: serum creatinine (relative risk [RR], 3.12 per 100-µM increase), proteinuria (RR, 1.64 per 1-g/24 hr increase), and pulse pressure (RR, 1.12 per 10 mm Hg), whereas age was a protective factor. With patient death in the composite endpoint, diabetes mellitus, smoking, age, and number of transplantations were also risk factors. Conclusions. Independent risk factors for graft loss or doubling of serum creatinine or patient death are mainly related to renal transplant function, proteinuria, and blood pressure, which emphasizes the importance of renoprotective treatment regimens in this population.

  • 67.
    Fraley, Alexander E
    et al.
    University of California.
    Schwartz, Gregory G
    University of Colorado.
    Olsson, Anders
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Kinlay, Scott
    Harvard University.
    Szarek, Michael
    Pfizer Pharmaceutical Grp.
    Rifai, Nader
    Harvard University.
    Libby, Peter
    Brigham & Womens Hospital.
    Ganz, Peter
    Brigham & Womens Hospital.
    Witztum, Joseph L
    University of California.
    Tsimikas, Sotirios
    University of California.
    Relationship of Oxidized Phospholipids and Biomarkers of Oxidized Low- Density Lipoprotein With Cardiovascular Risk Factors, Inflammatory Biomarkers, and Effect of Statin Therapy in Patients With Acute Coronary Syndromes Results From the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) Trial2009In: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, ISSN 0735-1097, Vol. 53, no 23, p. 2186-2196Article in journal (Refereed)
    Abstract [en]

    Objectives This study sought to define the relationship between oxidative biomarkers, cardiovascular disease (CVD) risk factors, and inflammatory and thrombosis biomarkers. Background Elevated levels of oxidized phospholipids (OxPL) on apolipoprotein B particles (apoB) represent a novel biomarker of CVD. Previous studies suggest that an increase in OxPL/apoB reflects a positive response to statins and a low-fat diet. Methods This study measured OxPL/apoB, lipoprotein (a) [Lp(a)], and oxidized low-density lipoprotein (OxLDL) biomarkers, consisting of immunoglobulin (Ig) G and IgM autoantibodies to malondialdehyde (MDA)-low-density lipoprotein (LDL) and IgG and IgM apoB-100 immune complexes (IC/apoB), at baseline and after 16 weeks of treatment with atorvastatin 80 mg/day or placebo in 2,342 patients with acute coronary syndromes (ACS) enrolled in the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) trial. Results At baseline, potentially atheroprotective IgM autoantibodies and IgM IC/apoB were lower in male patients, diabetic patients, and patients andgt;65 years of age. Patients with an LDL level greater than the median (122 mg/dl) had higher levels of OxPL/apoB, Lp(a), and OxLDL biomarkers compared with those who had an LDL level less than the median. Atorvastatin resulted in significantly larger changes in all biomarkers in female patients, patients age andlt;65 years, patients with LDL cholesterol andlt;122 mg/dl, nonsmokers, and nondiabetic patients (p andlt; 0.0001 for all). In particular, a significant increase in OxPL/apoB in response to atorvastatin was noted in all 20 subgroups evaluated. Weak or no significant correlations were noted between all OxLDL biomarkers and C-reactive protein, serum amyloid A, tissue plasminogen activator, interleukin-6, intercellular adhesion molecule, vascular cell adhesion molecule, P-selectin, and E-selectin at randomization and 16 weeks. Conclusions In patients with ACS, baseline levels of oxidative biomarkers varied according to specific CVD risk factors and were largely independent of inflammatory biomarkers. Atorvastatin uniformly increased OxPL/apoB levels in all subgroups studied. Future studies are warranted to assess whether the increase in OxPL/apoB levels reflects the benefit of effective therapeutic interventions and prediction of new CVD events.

  • 68.
    Franck, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. 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.
    Åstrand, Olov
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    The Ala isoform of the PPARγ Pro12Ala polymorphism is related to increased abdominal obesity in men but has little impact on cardiovascular risk markers in patients with type 2 diabetes2009Article in journal (Other academic)
    Abstract [en]

    Background: The interaction of the PPARγ Pro12Ala with obesity and cardiovascular risk is controversial. We aimed to study potential associations of the Ala isoform of this polymorphism with obesity, blood pressure and markers of cardiovascular disease and organ damage in middle aged patients with type 2 diabetes.

    Subjects and methods: We recruited 148 women and 246 men in the CArdiovascular Risk factors in Patients with DIabetes – a Prospective study in the Primary health care setting (CARDIPP) study in which early markers of organ damage by cardiac echocardiography, determination of carotid intima media thickness (IMT) and measurement of pulse wave velocity (PWV) was performed. Blood pressures were measured as both as 24-hour ambulatory blood pressure and as a noninvasive recording of central blood pressure. Allelic discrimination was detected with the ABI prism 7500HT Sequence Detection System. Due to the low prevalence of Ala homozygotes, heterozygotes and homozygotes of Ala were defined as Ala isoform in the analyses.

    Results: Men with Ala isoform exhibited higher sagittal abdominal diameter (Pro: 25.4±3.4 cm, Ala: 26.7±4.9 cm, p= 0.04) waist circumference (Pro: 104±11 cm, Ala: 108±15 cm, p= 0.046) and body weight (Pro: 91.6±14, Ala: 96.5±18, p= 0.035) than homozygotes for the Pro isoform. However, there were no differences in either gender with respect to blood pressures, left-ventricular mass-index, carotid IMT or carotid-femoral PWV in the participants.

    Conclusion: It is unlikely that determination of the PPARγ Pro12Ala isoform in clinic practice adds any major information on cardiovascular risk or circulatory organ damage in patients with type 2 diabetes.

  • 69.
    Fransson, Martin
    et al.
    Linköping University, Department of Computer and Information Science, PELAB - Programming Environment Laboratory. Linköping University, The Institute of Technology.
    Fritzson, Peter
    Linköping University, Department of Computer and Information Science, PELAB - Programming Environment Laboratory. Linköping University, The Institute of Technology.
    Lindqvist Appell, Malin
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Hindorf, Ulf
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    A preliminary study of modeling and simulation in individualized drug dosage – azathioprine on inflammatory bowel disease2007In: SIMS 2006: Proceedings of the 47th Conference on Simulation and Modelling, Helsinki, Finland, Helsinki: Kopio Niini Oy , 2007, p. 216-220Conference paper (Refereed)
    Abstract [en]

    Individualized drug dosage based on population pharmacokinetic/dynamic models is an important future technology used to reduce or eliminate side effects of certain drugs, e.g. cancer drugs. In this paper we report preliminary results from work-in-progress: a simplified linear model of the metabolism of a cancer treatment drug was estimated from experimental data. The model was then validated against the same data as a test of the adequacy of the model structure. From this investigation it became apparent that the model structure could not be used due to its inability to recreate the dynamic properties of the system.

  • 70.
    Franzen, L.
    et al.
    Department of Pathology, Clinical Research Centre, University Hospital Örebro, Örebro, Sweden.
    Ekstedt, Mattias
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Kechagias, Stergios
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bodin, L.
    Unit of Biostatistics and Epidemiology, Clinical Research Centre, University Hospital, Örebro, Sweden.
    Fiorini, R.N.
    Fiorini, R.N..
    Kirtz, J.
    Kirtz, J..
    Periyasamy, B.
    Periyasamy, B..
    Evans, Z.
    Evans, Z..
    Haines, J.
    Haines, J..
    Cheng, G.
    Cheng, G..
    Polito, C.
    Polito, C..
    Rodwell, D.
    Rodwell, D..
    Zhou, X.
    Zhou, X..
    Campbell, C.
    Campbell, C..
    Birsner, J.
    Birsner, J..
    Schmidt, M.G.
    Schmidt, M.G..
    Lewin, D.
    Lewin, D..
    Chavin, K.D.
    Chavin, K.D..
    Letter to the editor (multiple letter)2005In: Clinical Transplantation, ISSN 0902-0063, E-ISSN 1399-0012, Vol. 19, no 4, p. 571-572p. 571-Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 71.
    Franzén, Lennart E
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Kechagias, Stergios
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bodin, Lennart
    Unit of Biostatistics and Epidemiology, Clinical Research Centre, University Hospital, Örebro, Sweden.
    Semiquantitative evaluation overestimates the degree of steatosis in liver biopsies: a comparison to stereological point counting.2005In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 18, no 7, p. 912-916Article in journal (Refereed)
    Abstract [en]

    The degree of steatosis in liver biopsies is usually assessed by a morphological semiquantitative approach in which the histopathologist uses a four-graded scale: 0-3 or none, slight, moderate and severe. Scores 1-3 are considered to correspond to fat deposition in <33, 33-66 and >66% of the hepatocytes. There is a considerable inter- and intra-individual variation in such scoring methods and a more standardized and quantitative approach is preferable. In the present study, we compare the semiquantitative technique with the stereological point counting method in the assessment of hepatic steatosis. A total of 75 archived liver needle biopsies were used. They were selected according to the original routine diagnosis of slight, moderate or severe steatosis. In all, 10 randomly selected images from each biopsy were digitized into a computer, a point grid lattice was superimposed and the number of hits on fat globules was counted. A pathologist scored the specimens in a four-graded scale as described above. The mean liver biopsy area (volume) with fat in hepatocytes was 2.2% for grade 1, 9.2% for grade 2 and 23.1% for grade 3. The kappa value for the semiquantitative estimates was 0.71 for the unweigthed kappa and 0.87 for weighted kappa. The intraclass correlation coefficient (ICC) was 0.99 for images counted twice and 0.95 when two sets of images were captured from the same biopsy. These ICCs indicate excellent agreement and above that of the semiquantitative estimates. In conclusion, the area/volume of fat content of the hepatocytes is greatly overemphasized in semiquantitative estimation. Furthermore, the point counting technique has a better reproducibility than visual evaluation and should be preferred in estimates of liver steatosis in scientific studies and in clinical contexts when the amount of steatosis is important for treatment and prognosis, such as liver transplantation.

  • 72.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Johan Östgren, Carl
    Linköping University, Department of Medicine and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Finspång, Primary Health Care Centre.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Reduced Arteriovenous Shunting Capacity After Local Heating and Redistribution of Baseline Skin Blood Flow in Type 2 Diabetes Assessed With Velocity-Resolved Quantitative Laser Doppler Flowmetry2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 7, p. 1578-1584Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-To compare the microcirculatory velocity distribution in type 2 diabetic patients and nondiabetic control subjects at baseline and after local heating. RESEARCH DESIGN AND METHODS-The skin blood flow response to local heating (44 degrees C for 20 mm) was assessed in 28 diabetic patients and 29 control subjects using a new velocity-resolved quantitative laser Doppler flowmetry technique (qLDF). The qLDF estimates erythrocyte (RBC) perfusion (velocity X concentration), in a physiologically relevant unit (grams RBC per 100 g tissue X millimeters per second) in a fixed output volume, separated into three velocity regions: v less than1 mm/s, v 1-10 mm/s, and v greater than10 mm/s. RESULTS-The increased blood flow occurs in vessels with a velocity greater than1 mm/s. A significantly lower response in qLDF total perfusion was found in diabetic patients than in control subjects after heat provocation because of less high-velocity blood flow (v greater than10 mm/s). The RBC concentration in diabetic patients increased sevenfold for v between 1 and 10 mm/s, and 15-fold for v greater than10 mm/s, whereas no significant increase was found for v less than1 mm/s. The mean velocity increased from 0.94 to 7.3 mm/s in diabetic patients and from 0.83 to 9.7 mm/s in control subjects. CONCLUSIONS-The perfusion increase occurs in larger shunting vessels and not as an increase in capillary flow. Baseline diabetic patient data indicated a redistribution of flow to higher velocity regions, associated with longer duration of diabetes. A lower perfusion was associated with a higher BMI and a lower toe-to-brachial systolic blood pressure ratio.

  • 73.
    G Olsson, Anders
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Lipid lowering and aortic valve disease2009In: CURRENT ATHEROSCLEROSIS REPORTS, ISSN 1523-3804, Vol. 11, no 5, p. 377-383Article in journal (Refereed)
    Abstract [en]

    Several retrospective and nonrandomized studies have indicated that lowering atherogenic lipoprotein, in particular low-density lipoprotein cholesterol, may retard the hemodynamic progression of aortic stenosis (AS). This valvular disease shares pathogenic and pathoanatomic similarities with atherosclerosis, at least in their early developments. Two randomized placebo-controlled studies researching the effect of lowering low-density lipoprotein on AS progression and its clinical consequences have been published recently-the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (SALTIRE) study and the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Both of these studies had neutral outcomes. The causes for the negative outcome may be that cholesterol lowering does not influence AS development in a clinically significant way or it may be due to traits in the design of the studies or treatments. Therefore, statin treatment for prevention of AS progression cannot be ruled out as a future therapeutic option in AS. The outcome of the ongoing Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) study, which is examining lipid lowering as a treatment for AS, is greatly anticipated.

  • 74.
    Garvin, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Kristenson, Margareta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    Nijm, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Psychosocial factors in atherosclerosis2006In: XIV International Symposium on Atherosclerosis,2006, 2006Conference paper (Other academic)
  • 75. Gasche, C
    et al.
    Berstad, A
    Befrits, R
    Beglinger, C
    Dignass, A
    Erichsen, K
    Gomollon, F
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Koutroubakis, I
    Kulnigg, S
    Oldenburg, B
    Rampton, D
    Schroeder, O
    Stein, J
    Travis, S
    Van Assche, G
    Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases2007In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 13, no 12, p. 1545-1553Article in journal (Refereed)
    Abstract [en]

    Anemia is a common complication of inflammatory bowel diseases. An international working party has formed and developed guidelines for evaluation and treatment of anemia and iron deficiency that should serve practicing gastroenterologists. Within a total of 16 statements, recommendations are made regarding diagnostic measures to screen for iron- and other anemia-related deficiencies regarding the triggers for medical intervention, treatment goals, and appropriate therapies. Anemia is a common cause of hospitalization, prevents physicians from discharging hospitalized patients, and is one of me most frequent comorbid conditions in patients with inflammatory bowel disease. It therefore needs appropriate attention and specific care. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

  • 76.
    Gotto, AM
    et al.
    Care Of Jou J, Cornell Univ, Weill Med Coll, New York, NY 10021 USA Linkoping Univ Hosp, Clin Res Ctr, S-58185 Linkoping, Sweden.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    A symposium: In Search of the Ideal Lipid-Lowering Agent - Introduction2001In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 87, no 5A, p. 1B-1BOther (Other academic)
  • 77.
    Grahn Kronhed, Ann-Charlotte
    et al.
    Linköping University, Department of Department of Health and Society. Linköping University, Faculty of Health Sciences.
    Angbratt, Marianne
    Linköping University, Department of Department of Health and Society. Linköping University, Faculty of Health Sciences.
    Blomberg, Carina
    Toss, Göran
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Waller, John
    Möller, Margareta
    Research and Development Unit, Primary Health Care, BorÅs, Sweden.
    Association between physical activity and forearm bone mineral density in 20-72-year-olds2002In: Advances in Physiotherapy, ISSN 1403-8196, E-ISSN 1651-1948, Vol. 4, no 2, p. 87-96Article in journal (Refereed)
    Abstract [en]

    Physical activity may influence bone mineral density (BMD) in different ways. In the present study the amount of physical activity and the associations between forearm BMD, body mass index, physical activity and several other lifestyle factors were explored. A random sample of the population in a Swedish municipality was invited to the study and examined by a questionnaire and by forearm bone mineral measurements using single photon absorptiometry. Forearm BMD was measured in 880 subjects. Forearm BMD was stable from 20 to 50 years of age in women and from 20 to 60 years of age in men. Reported moderate leisure-time physical activity levels in men were significantly associated with higher forearm BMD than low leisure-time physical activity levels ( p = 0.042). The findings that moderate levels of leisure-time physical activity in men were associated with higher forearm BMD, give some support to the hypothesis that increased amount of physical activity in a population might be of benefit in the prevention of osteoporosis. Further longitudinal studies of the effect of physical activity in the prevention of osteoporosis, falls and fractures are warranted.

  • 78.
    Haglund, Sofie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Söderman, Jan
    Division of Medical Diagnostics, Laboratory medicine, Ryhov Hospital, Jönköping, Sweden.
    Pharmacotranscriptomics in thiopurine treated IBD patients with different metabolite profiles2008Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Thiopurine drugs are used to induce and maintain remission in inflammatory bowel disease. The methyl thioinosine monophosphate (meTIMP)/6-thioguanine nucleotide (6-TGN) concentration ratio has been related to drug response and adverse reactions. Here we investigated for differences in gene expression levels between patients with different metabolite profiles.

    Methods: Transcriptional profiles in blood samples from an exploratory patient cohort (n=21) comprising three groups; patients with normal thiopurine S-methyltransferase phenotype and meTIMP/6-TGN concentration ratio >20, ratio 10.0-14.0 and ratio ≤4, respectively, were assessed by hybridization to microarrays. Results were further evaluated with reverse transcription qPCR [exploratory and a validation cohort of patients (n=33)]. Additionally, known genes of the thiopurine metabolic pathway were analysed separately.

    Results: The whole genome expression analysis did not identify any significant differences between metabolite profiles. Analysis of thiopurine related genes revealed a large interindividual variation in gene expression, but only small differences between metabolite profiles. Three clusters of co-regulated genes were defined based on correlations between gene expression levels. The concentration of meTIMP correlated to the expression of NT5E (rs = 0.33, P = 0.02) and TPMT (rs = - 0.37, P = 0.007). The concentration of 6-TGN correlated to the expression of HPRT1 (rs = - 0.31, P = 0.03) and SLC29A1 (rs = 0.33, P = 0.02). With the exception of SLC29A1, these genes belonged to the same cluster of genes.

    Conclusions: Our results illustrates the complexity of the thiopurine metabolism and suggest that differences between metabolite profiles are explained either by interactions between several genes, each with a small contribution, or at the post-transcriptional level. Search for more precise tools in order to explain differences in metabolite profiles is needed.

  • 79.
    Haglund, Sofie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Lindqvist Appell, Malin
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Taipalensuu, J.
    Div. of R. and D. in Lab. Medicine, Ryhov County Hospital, SE-551 85 Jönköping, Sweden.
    Pyrosequencing of TPMT Alleles in a General Swedish Population and in Patients with Inflammatory Bowel Disease2004In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 50, no 2, p. 288-295Article in journal (Refereed)
    Abstract [en]

    Background: Interindividual differences in therapeutic efficacy in patients treated with thiopurines might be explained by the presence of thiopurine S-methyltransferase (TPMT) alleles that encode for reduced TPMT enzymatic activity. It is therefore of value to know an individual's inherent capacity to express TPMT. Method: We developed a pyrosequencing method to detect 10 single-nucleotide polymorphisms (SNPs) in TPMT. A Swedish population (n = 800) was examined for TPMT*3A, TPMT*3B, TPMT*3C, and TPMT*2. Patients with inflammatory bowel disease (n = 24) and healthy volunteers (n = 6), selected on the basis of TPMT enzymatic activity, were investigated for all 10 SNPs to determine the relationship between TPMT genotype and phenotype. Results: In the general population we identified the following genotypes with nonfunctional alleles: TPMT*1/*3A (*3A allelic frequency, 3.75%), TPMT*1/*3C (*3C allelic frequency, 0.44%), TPMT*1/*3B (*3B allelic frequency, 0.13%), and TPMT*1/*2 (*2 allelic frequency, 0.06%). All nine individuals with normal enzymatic activity were wild-type TPMT*1/*1. Thirteen individuals with intermediate activity were either TPMT*1/*3A (n = 12) or TPMT*1/*2 (n = 1). Eight individuals with low enzymatic activity were TPMT*3A/*3A (n = 4), TPMT*3A/*3C (n = 2), or TPMT*1/*3A (n = 2). Conclusion: Next to wild type, the most frequent alleles in Sweden are TPMT*3A and TPMT*3C. A previously established phenotypic cutoff for distinguishing normal from intermediate metabolizers was confirmed. To identify the majority of cases (90%) with low or intermediate TPMT activity, it was sufficient to analyze individuals for only 3 of the 10 SNPs investigated. Nevertheless, this investigation indicates that other mutations might be of relevance for decreased enzymatic activity. © 2004 American Association for Clinical Chemistry.

  • 80.
    Haglund, Sofie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Taipalensuu, Jan
    1Research and Development in Laboratory Medicine Laboratory Medicine, Ryhov Hospital, Jönköping.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    IMPDH activity in thiopurine-treated patients with inflammatory bowel disease - Relation to TPMT activity and metabolite concentrations2008In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 65, no 1, p. 69-77Article in journal (Refereed)
    Abstract [en]

    AIMS: Azathioprine and 6-mercaptopurine are steroid-sparing drugs used in inflammatory bowel disease (IBD). The polymorphic enzyme thiopurine S-methyltransferase (TPMT) is of importance for thiopurine metabolism and occurrence of adverse events. The role of other thiopurine-metabolizing enzymes is less well known. This study investigated the role of inosine-5′- monophosphate dehydrogenase (IMPDH), which is a key enzyme in the de novo synthesis of guanine nucleotides and also strategically positioned in the metabolic pathway of thiopurines. METHODS: IMPDH was measured in 100 healthy blood donors. IMPDH, TPMT and metabolite concentrations were studied in 50 patients with IBD on stable thiopurine therapy. IMPDH activity was measured in peripheral blood mononuclear cells. TPMT activity, 6-methylthioinosine 5′-monophosphate (meTIMP) and 6-thioguanine nucleotide (6-TGN) concentrations were measured in red blod cells, which is the current practice in clinical monitoring of thiopurines. Enzyme activities were related to metabolite concentrations and clinical characteristics. RESULTS: A wide range of IMPDH activity was observed both in healthy blood donors (median 13.1, range 4.7-24.2 nmol mg-1 protein h-1) and IBD patients (median 14.0, range 7.0-21.7). There was a negative correlation between IMPDH activity and dose-normalized meTIMP concentrations (rs = -0.31, P = 0.03), but no evident correlation to 6-TGN concentration or the meTIMP/6-TGN ratio. There were no significant correlations between TPMT activity and metabolite concentrations. CONCLUSION: Even though the meTIMP concentrations correlated inversely to the IMPDH activity, the role of IMPDH in balancing the formation of methylated and phosphorylated metabolites was not evident. Taken together, the results give cause to question established opinions about thiopurine metabolism. © 2007 The Authors.

  • 81. Hallberg, I
    et al.
    Lofman, O
    Wahlstrom, O
    Toss, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Quality of life after different types of osteoporotic fractures.2001In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 16, p. S393-S393Conference paper (Other academic)
  • 82.
    Hallberg, Inger
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Ek, Anna-Christina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Toss, Göran
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    A striving for independence: a qualitative study of women living with vertebral fracture2010In: BMC Nursing, ISSN 1472-6955, E-ISSN 1472-6955, Vol. 9, no 7Article in journal (Refereed)
    Abstract [en]

    Background

    Quantitative studies using generic and disease-specific health-related quality of life (HRQOL) questionnaires have shown that osteoporosis-related vertebral fractures have a significant negative effect on HRQOL, but there are only few studies that address what it means to live with vertebral fracture from a deeper experiential perspective. How HRQOL and daily life are affected several years after vertebral fracture and how women cope with this are more unclear. This study aimed to describe how HRQOL and daily life had been affected in women with vertebral fracture several years after diagnosis.

    Methods

    The study design was qualitative. Semi-structured interviews were conducted with ten Swedish women during 2008. Data were analysed using qualitative inductive content analysis.

    Results

    The findings of this study revealed three themes related to the influence on HRQOL and daily life: A threatened independence, i.e. back pain, anxiety, negative impact on self-image and consequences in daily life; Strategies for maintaining independence, i.e. coping, self-care and support; and The importance of maintaining independence, i.e. the ability to perform everyday activities, social interaction and having something meaningful to do. The women were striving for independence or maintaining their independence by trying to manage different types of symptoms and consequences in different ways.

    Conclusion

    HRQOL and daily life were strongly affected in a negative way by the impact of the vertebral fracture. Information from this study may provide new knowledge and understanding of the women's experiences of living with vertebral fracture from an insider's point of view in order to obtain a deeper understanding of the women's everyday life. However, further evaluation is still needed in larger study groups.

  • 83.
    Hallberg, Inger
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Rosenqvist, A. M
    Department of Geriatrics, Ryhovs Hospital, Jönköping, Sweden.
    Kartous, L
    Department of Geriatrics, Ryhovs Hospital, Jönköping, Sweden.
    Löfman, Owe
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    Wahlström, Ola
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Toss, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Health-related quality of life after osteoporotic fractures2004In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 15, no 10, p. 834-841Article in journal (Refereed)
    Abstract [en]

    Objective: To estimate the impact of osteoporosis fractures on health-related quality of life (HRQOL) in postmenopausal women. Methods: To compare the impact on HRQOL of different osteoporotic fractures, 600 consecutive women 55-75 years old with a new fracture (inclusion fracture) were invited by mail. After exclusions by preset criteria (high-energy fractures, ongoing osteoporosis treatment, or unwillingness to participate), 303 women were included, 171 (56%) of whom had a forearm, 37 (12%) proximal humerus, 40 (13%) hip, and 55 (18%) vertebral fracture, respectively, and all were investigated and treated according to the current local consensus program for osteoporosis. In addition, HRQOL was evaluated by the SF-36 questionnaire and compared with local, age-matched reference material. Examinations were performed 82 days (median) after the fracture and 2 years later. Results: HRQOL was significantly reduced at baseline regarding all SF-36 domains after vertebral fractures and most after hip fractures, but only regarding some domains after forearm and humerus fracture. After 2 years, improvements had occurred after all types of fractures, and after forearm or humerus fracture, HRQOL was completely normalized in all domains. However, 2 years after hip fracture, HRQOL was still below normal regarding physical function, role-physical and social function, while after vertebral fracture, scores were still significantly lower for all domains, physical as well as mental. Patients with one or more previous fractures before the inclusion fracture had lower HRQOL at baseline and after 2 years, compared with those with no previous fracture. Patients with osteoporosis (T-score < - 2.5 in hip or spine) had lower HRQOL than those with normal BMD. Conclusion: Vertebral and hip fractures have a considerably greater and more prolonged impact on HRQOL than forearm and humerus fractures. The number of fractures was inversely correlated to HRQOL. These differences should be taken into account when making priorities in health care programs.

  • 84. Hallberg, P
    et al.
    Karlsson, J
    Lind, L
    Michaelsson, K
    Kurland, L
    Kahan, T
    Malmqvist, K
    Ohman, KP
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Liljedahl, U
    Syvanen, AC
    Melhus, H
    Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment - results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)2004In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 27, p. 287-290Article in journal (Refereed)
  • 85. Hallberg, P
    et al.
    Lind, L
    Billberger, K
    Michaelsson, K
    Karlsson, J
    Kurland, L
    Kahan, T
    Malmqvist, K
    Ohman, KP
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Liljedahl, U
    Syvanen, AC
    Melhus, H
    Transforming growth factor beta1 genotype and change in left ventricular mass during antipypertensive treatment - results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)2004In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 27, p. 169-173Article in journal (Refereed)
  • 86.
    Hedman, Christina
    et al.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Frystyk, J
    Aarhus University Hospital.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Oskarsson, P
    Karolinska University.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Intraperitoneal insulin delivery gives higher circulating IGF-I activity than CSII in type 1 diabetes2009In: in DIABETOLOGIA, vol 52, 2009, Vol. 52, p. S376-S377Conference paper (Refereed)
    Abstract [en]

    n/a

  • 87.
    Hindorf, U
    et al.
    Lund University Hospital.
    Johansson, M
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Eriksson, A
    Sahlgrens University Hospital.
    Kvifors, E
    Sahlgrens University Hospital.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Mercaptopurine treatment should be considered in azathioprine intolerant patients with inflammatory bowel disease2009In: ALIMENTARY PHARMACOLOGY and THERAPEUTICS, ISSN 0269-2813, Vol. 29, no 6, p. 654-661Article in journal (Refereed)
    Abstract [en]

    Adverse drug reactions are a significant reason for therapeutic failure during thiopurine treatment of inflammatory bowel disease. Some smaller series in this patient population have shown that a switch to mercaptopurine may be successful in many cases of azathioprine intolerance.

    To assess the long-term outcome of mercaptopurine treatment in a large patient population with azathioprine intolerance.

    We identified 135 patients (74 women; median age 40 years) with Crohns disease (n = 88) or ulcerative colitis (n = 47) and reviewed their medical records.

    A total of 70 patients (52%) tolerated mercaptopurine and were followed up for 736 (362-1080) days; 65 patients discontinued mercaptopurine due to adverse events after 25 (8-92) days. Mercaptopurine was tolerated in 71% (12/17) with hepatotoxicity and in 68% (13/19) with arthralgia/myalgia during azathioprine treatment. Previous abdominal surgery was more common in mercaptopurine intolerant patients [39/65 (60%) vs. 27/70 (39%); P = 0.02] and thiopurine methyltransferase activity was higher in mercaptopurine tolerant patients than in mercaptopurine intolerant patients [13.2 (11.4-15.3) vs. 11.8 (9.6-14.2) U/mL red blood cells; P = 0.04; n = 81].

    A trial of mercaptopurine should be considered in azathioprine intolerance, as half of the patients tolerate a switch to mercaptopurine. Patients with hepatotoxicity or arthralgia/myalgia during azathioprine treatment might benefit more often than those with other types of adverse events.

  • 88.
    Hindorf, U.
    et al.
    Division of Gastroenterology, Department of Internal Medicine, University Hospital, Lund, Sweden, Division of Gastroenterology, Department of Internal Medicine, University Hospital, SE-221 85 Lund, Sweden.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Assessment of thiopurine methyltransferase and metabolite formation during thiopurine therapy: Results from a large swedish patient population2004In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 26, no 6, p. 673-678Article in journal (Refereed)
    Abstract [en]

    This study examined thiopurine methyltransferase (TPMT) and the relationship to thioguanine nucleotides (TGN) and methylthioinosine monophosphate (meTIMP) in a large Swedish patient population. The current hypothesis is that the cytotoxic effects of thiopurine drugs are mediated by the incorporation of TGN into DNA. The authors assayed the TPMT activity in red blood cells from 1151 subjects and the concentrations of TGN (n = 602) and meTIMP (n = 593) from patients treated with thiopurine drugs. The TPMT frequency distribution in both adults and children showed some differences from what had been found in unselected general populations. Children had lower median TPMT activity than adults (12.0 versus 12.9 U/mL RBC, P < 0.001). Relative differences in both TGN formation [medians: normal TPMT, 1.3, intermediate TPMT, 3.3, low TPMT, 47.9 pmol/8 × 108 RBC per mg azathioprine (AZA), P < 0.001] and meTIMP formation (medians: normal TPMT, 13, intermediate TPMT, 7.3, low TPMT, 0 pmol/8 × 108 RBC per mg AZA, P = 0.001) per 1 mg administered drug were noted among the 3 TPMT activity groups. Women formed higher concentrations of both TGN (1.5 versus 1.3 pmol/8 × 108 RBC per mg AZA, P = 0.01) and meTIMP (14.4 versus 10.7 pmol/8 × 108 RBC per mg AZA, P = 0.01) than men did. There was a significant correlation between the AZA dose and the meTIMP concentrations (r = 0.45, P < 0.001). Furthermore, dose alterations made in subjects with normal TPMT (n = 84) and intermediate TPMT (n = 22) activity resulted in more pronounced increases in TGN concentrations (170 versus 30 pmol/8 × 10 8 RBC, P < 0.001) in intermediate TPMT activity, whereas in normal TPMT activity changes in meTIMP concentrations were more pronounced (1.3 versus 0 nmol/8 × 108 RBC, P < 0.001). In normal TPMT activity both metabolites increased in a dose-dependent fashion, whereas in intermediate TPMT activity only TGN concentrations increased. The results of this study demonstrate the dynamic nature of thiopurine metabolism and its importance for thiopurine dosing.

  • 89. Hindorf, U
    et al.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Assessment of Thiopurine Methyltransferase and Metabolite Formation During Thiopurine Therapy: Results from a Large Swedish Patient Population2004In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 26, p. 673-678Article in journal (Refereed)
  • 90.
    Hindorf, Ulf
    et al.
    Lund University Hospital.
    Jahed, Khatoon
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Bergquist, Annika
    Karolinska University Hospital.
    Verbaan, Hans
    Malmo University Hospital.
    Prytz, Hanne
    Lund University Hospital.
    Wallerstedt, Sven
    Sahlgrens University Hospital.
    Werner, Marten
    Umeå University Hospital.
    Olsson, Rolf
    Sahlgrenska University Hospital.
    Bjoernsson, Einar
    Sahlgrenska University Hospital.
    Peterson, Curt
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Characterisation and utility of thiopurine methyltransferase and thiopurine metabolite measurements in autoimmune hepatitis2010In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 52, no 1, p. 106-111Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Corticosteroids alone or in conjunction with azathioprine (AZA) is the standard treatment in autoimmune hepatitis (AiH). Individual variations in thiopurine (TP) metabolism may affect both drug efficacy and toxicity. Our aim was to investigate the utility of thiopurine methyl transferase (TPMT) as well as thioguanine nucleotide (TGN) and methylthioinosine monophosphate (meTIMP) metabolite measurements with regard to clinical outcome. Methods: Two hundred thirty-eight patients with AM were included in this cross-sectional study. TPMT status was assessed in all patients, while TGN and meTIMP were measured in patients with ongoing TP medication. Clinical outcome was evaluated by liver tests and the ability to withdraw steroids. Results: TPMT genotyping (n = 229) revealed 207 (90.4%) wildtype and 22 heterozygous patients. One hundred forty-three patients had ongoing TP therapy with AZA (n = 134) or mercaptopurine (MP; n = 9): response was judged as complete response (CR) in 113 patients and partial response (PR) in 30 patients. Both TP dose (1.64 vs 1.19 mg/kg; p = 0.012) and TPMT activity (14.3 vs 13.5; p = 0.05) were higher in PR, resulting in similar TGN levels (PR: 121 pmol/8 x 10(8) red blood cells [RBC]; CR: 113 pmol/8 x 10(8) RBC; p = 0.33) but higher meTIMP levels in PR (1350 vs 400 pmol/8 x 10(8) RBC; p = 0.004). Patients able to withdraw steroids or who were using less than= 5 mg prednisolone daily were treated with lower TP doses than patients on higher steroid doses (1.15 vs 1.18 vs 1.82 mg/kg; p less than 0.001). Conclusions: TP metabolite measurements are of clinical value in AM patients who do not respond to standard TP treatment and for the identification of a shifted metabolism, which may demand an alternative treatment strategy.

  • 91.
    Hindorf, Ulf
    et al.
    Lund.
    Lindqvist Appell, Malin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hildebrand, Hans
    Stockholm.
    Fagerberg, Ulrika
    Stockolm.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease2006In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 24, no 2, p. 331-342Article in journal (Refereed)
    Abstract [en]

    Background: Adverse events leading to discontinuation or dose reduction of thiopurine therapy occur in 9-28% of patients with inflammatory bowel disease. Aims: To evaluate the influence of thiopurine methyltransferase status and thiopurine metabolites in a large patient population for the risk of developing adverse event. Methods: Three hundred and sixty-four patients with inflammatory bowel disease and present or previous thiopurine therapy were identified from a local database. Results: The adverse event observed in 124 patients (34%) were more common in adults than children (40% vs. 15%, P < 0.001) and in low to intermediate (≤9.0 U/mL red blood cell) than normal thiopurine methyltransferase activity (P = 0.02). Myelotoxicity developed later than other types of adverse event. An increased frequency of adverse event was observed in patients with tioguanine (thioguanine) nucleotide above 400 or methylated thioinosine monophosphate above 11 450 pmol/ 8 × 108 red blood cell. A shift to mercaptopurine was successful in 48% of azathioprine-intolerant patients and in all cases of azathioprine-induced myalgia or arthralgia. Conclusions: A pre-treatment determination of thiopurine methyltransferase status might be appropriate as patients with low to intermediate thiopurine methyltransferase activity are more prone to develop an adverse event, determination of metabolite levels can be useful in the case of an adverse event. Mercaptopurine therapy should be considered in azathioprine-intolerant patients. © 2006 The Authors.

  • 92.
    Hindorf, Ulf
    et al.
    Lund .
    Lindqvist Appell, Malin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Pousette, A
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease2006In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, no 10, p. 1423-1431Article in journal (Refereed)
    Abstract [en]

    Background: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)), 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio, p = 0.02). Patients with meTIMP concentrations > 11 450 pmol/8 × 108 red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0, p = 0.015). Conclusions: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.

  • 93.
    Hindorf, Ulf
    et al.
    Lunds Universitet.
    Lindqvist Appell, Malin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Molecular and Clinical Medicine.
    Pousette, Anneli
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    High methylthioinosine monophosphate levels as a cause of myelotoxicity when introducing thiopurine therapy in patients with inflammatory bowel disease2005In: 13th United European Gastroenterology week,2005, Stuttgart: Georg Thieme Verlag KG , 2005, p. A169-Conference paper (Refereed)
  • 94. Hirsch, Mark
    et al.
    O´Donnell, John
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Rosuvastatin is cost-effective compared with atorvastatin in reaching cholesterol goals2005In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 104, no 3, p. 251-256Article in journal (Refereed)
    Abstract [en]

    Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of coronary heart disease. The introduction of a highly efficacious new statin, rosuvastatin, may enable more patients to be treated to LDL-C goal within a fixed budget. Objectives: To compare the cost-effectiveness of rosuvastatin 10 mg and atorvastatin 10 mg in lowering LDL-C and achieving guideline goals after 12 weeks of treatment. The LDL-C goals were those recommended by the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III and the Third Joint European Task Force. Methods: The analysis was performed on pooled data from three clinical trials. Efficacy was measured as the percent reduction in LDL-C and the proportion of patients who reached guideline LDL-C goals following the first 12 weeks of treatment, prior to dose titration. Costs comprised drug acquisition costs only. The cost-effectiveness measures were cost per 1% reduction in LDL-C and cost per patient treated to their LDL-C goal. Results: Treatment with rosuvastatin 10 mg costs €1.85 per 1% reduction in LDL-C, compared with €2.37 per 1% reduction with atorvastatin 10 mg. The average costs per patient treated to the European LDL-C goals were €130.18 for rosuvastatin 10 mg and €242.44 for atorvastatin 10 mg. Treating to NCEP ATP III goals costs €115 per patient treated with rosuvastatin 10 mg vs. €163 per patient treated with atorvastatin 10 mg. Conclusions: Rosuvastatin has the same acquisition costs as and is more efficacious than atorvastatin in lowering LDL-C and treating patients to target LDL-C levels. © 2005 Elsevier Ireland Ltd. All rights reserved.

  • 95.
    Hjortswang, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Oxelmark, L.
    Institutionen för neurobiologi, Vårdvetenskap och samhälle, Karolinska institutet, Huddinge, Sweden.
    Sänkt livskvalitet vid skov grundar för alternativ terapi2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 45, p. 3010-3013Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 96.
    Hjortswang, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tysk, Curt
    Orebro Univ Hosp, Dept Med, Div Gastroenterol, Orebro, Sweden.
    Bohr, Johan
    Orebro Univ Hosp, Dept Med, Div Gastroenterol, Orebro, Sweden.
    Benoni, Cecilia
    MAS Univ Hosp, Dept Med, Div Gastroenterol, Malmo, Sweden.
    Kilander, Anders
    Sahlgrenska Univ Hospital, Div Gastroenterol, Dept Med, Gothenburg, Sweden.
    Larsson, Lasse
    Sahlgrenska Univ Hospital, Div Gastroenterol, Dept Med, Gothenburg, Sweden.
    Vigren, Lira
    MAS Univ Hosp, Dept Med, Div Gastroenterol, Malmo, Sweden.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Defining Clinical Criteria for Clinical Remission and Disease Activity in Collagenous Colitis2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1875-1881Article in journal (Refereed)
    Abstract [en]

    Background: Collagenous colitis is a chronic inflammatory bowel disease accompanied mainly by nonbloody diarrhea. The objectives of treatment are to alleviate the symptoms and minimize the deleterious effects on health-related quality of life (HRQOL). There is still no generally accepted clinical definition of remission or relapse. The purpose of this study was to analyze the impact of bowel symptoms on HRQOL and accordingly suggest criteria for remission and disease activity based on impact of patient symptoms on HRQOL. Methods: The design was a cross-sectional postal survey of 116 patients with collagenous colitis. The main outcome measures were 4 HRQOL questionnaires: the Short Health Scale, the Inflammatory Bowel Disease Questionnaire, the Rating Form of IBD Patient Concerns, and the Psychological General Well-Being Index, and a 1-week symptom diary recording number of stools/day and number of watery stools/day. Results: Severity of bowel symptoms had a deleterious impact on patients HRQOL. Patients with a mean of greater than= 3 stools/day or a mean of greater than= 1 watery stool/day had a significantly impaired HRQOL compared to those with less than3 stools/day and less than 1 watery stool/day. Conclusions: We propose that clinical remission in collagenous colitis is defined as a mean of less than3 stools/day and a mean of less than 1 watery stool per clay and disease activity to be a daily mean of greater than= 3 stools or a mean of greater than= 1 watery stool.

  • 97.
    Holdaas, H.
    et al.
    Rikshospitalet, Sognsvannsvn 20, Oslo 0072, Norway.
    Fellstrom, B.
    Fellström, B., University Hospital, Uppsala, Sweden.
    Jardine, A.G.
    University of Glasgow, Glasgow, United Kingdom.
    Holme, I.
    Preventive Medicine Clinic, Ullevaal University Hospital, Oslo, Norway.
    Nyberg, G.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Fauchald, P.
    Rikshospitalet, Sognsvannsvn 20, Oslo 0072, Norway.
    Gronhagen-Riska, C.
    Grönhagen-Riska, C., University Hospital, Helsinki, Finland.
    Madsen, S.
    Skejby Hospital, Aarhus, Denmark.
    Neumayer, H.-H.
    Univ. Klin. Charité, Berlin, Germany.
    Cole, E.
    Toronto General Hospital, Toronto, Ont., Canada.
    Maes, B.
    University Hospital, Leuven, Belgium.
    Ambuhl, P.
    Ambühl, P., University Hospital, Zürich, Switzerland.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hartmann, A.
    Rikshospitalet, Sognsvannsvn 20, Oslo 0072, Norway.
    Solbu, D.O.
    Novartis Norge AS, Oslo, Norway.
    Pedersen, T.R.
    Preventive Medicine Clinic, Ullevaal University Hospital, Oslo, Norway.
    Effect of fluvastatin on cardiac outcomes in renal transplant recipients: A multicentre, randomised, placebo-controlled trial2003In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 361, no 9374, p. 2024-2031Article in journal (Refereed)
    Abstract [en]

    Background: Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population. Methods: We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4·0-9·0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat. Findings: After a mean follow-up of 5·1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0·83 [95% CI 0·64-1·06], p=0·139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0·65 [0·48-0·88] p=0·005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups. Interpretation: Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.

  • 98.
    Hollman, Gunilla
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Ek, Anna-Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nursing Science.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Only one of four patients with familial hypercholesterolaemia reach cholesterol treatment goals in primary prevention2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 256, no 2, p. 176-177Article in journal (Other academic)
  • 99.
    Hollman, Gunilla
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nursing Science.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ek, Anna-Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nursing Science. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Disease knowledge and adherence to treatment in patients with familial hypercholesterolemia2006In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 21, no 2, p. 103-108Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Familial hypercholesterolemia (FH) is one of the most common genetic metabolic disorders and is associated with a high risk of premature coronary heart disease. Primary prevention directed at lifestyle changes, combined with preventive medical treatment, is the most important way to reduce the risk of coronary heart disease in individuals with FH. Knowledge about the condition and adherence to drug treatment may facilitate reaching treatment goals. OBJECTIVE: The purpose of this study was to describe disease knowledge and adherence to treatment in patients with FH. SUBJECTS AND METHODS: Seventy-four patients, more than 18 years of age, with FH were asked to participate. A questionnaire on disease knowledge about FH and adherence to drug treatment was sent to the patients. Response rate was 92% (n = 68). Drug treatment, laboratory results, blood pressure, and smoking were also documented. RESULTS: Most patients knew about cholesterol, prevention, and the reason for drug treatment but were less informed about the risk of genetic transmission and family history. No significant correlation was found between knowledge and low-density lipoprotein cholesterol level. A significant, negative correlation between adherence and low-density lipoprotein cholesterol level was found (r = -.354, P < .01). CONCLUSIONS: Patients with FH had scant understanding about the risk of genetic transmission and family history. High adherence to drug prescription has significant correlation to low-density lipoprotein cholesterol level. © 2006 Lippincott Williams & Wilkins, Inc.

  • 100.
    Holme, I
    et al.
    Oslo University Hospital.
    Fayyad, R
    Pfizer Inc.
    Faergeman, O
    Arhus University Hospital.
    Kastelein, J J P
    Acad Hospital.
    Olsson, Anders
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tikkanen, M J
    University Helsinki.
    Larsen, M L
    Arhus University Hospital.
    Lindahl, C
    Pfizer Sweden.
    Holdaas, H
    University of Oslo.
    Pedersen, T R
    Oslo University Hospital.
    Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: results from the IDEAL trial2010In: JOURNAL OF INTERNAL MEDICINE, ISSN 0954-6820, Vol. 267, no 6, p. 567-575Article in journal (Refereed)
    Abstract [en]

    Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: Results from the IDEAL trial. J Intern Med 2010; 267:567-575. Objectives. In Incremental Decrease in Endpoints through Aggressive Lipid-lowering (IDEAL), we compared cardiovascular outcomes in patients with and without chronic kidney disease (CKD) (estimated glomerular filtration rate andlt; 60 mL min-1 1.73 m-2) and analysed relationships between lipoprotein components (LC) and major coronary events (MCE) and other cardiovascular (CV) events. Design. Exploratory analysis of CV endpoints in a randomized trial comparing high dose of atorvastatin to usual dose of simvastatin on MCE. Settings. Patients with CKD were compared with the non-CKD patients. Cox regression models were used to study the relationships between on-treatment levels of LC and incident MCE. Findings. Chronic kidney disease was strongly associated with cardiovascular end-points including total mortality. In patients with CKD, a significant benefit of high dose atorvastatin treatment was found for any CV events, stroke and peripheral artery disease, but not for MCE. However, all cardiovascular end-points except stroke and CV mortality were reduced in the non-CKD group. Differential changes in LC or relationships to LC could not explain the different treatment outcomes in MCE in the two groups. Interpretation. Chronic kidney disease was a powerful risk factor for all cardiovascular end-points. The reason why the significant reductions achieved by high-dose statin treatment in most CV end-points in the non-CKD group were only in part matched by similar reductions in the CKD patients is not apparent. This difference did not result from differential changes in or relations to LC, but limited power may have increased the possibility of chance findings.

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