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  • 251. Pundziute-Lycka, A
    et al.
    Dahlquist, G
    Nystrom, L
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bjork, E
    Blohme, G
    Bolinder, J
    Eriksson, JW
    Sundkvist, G
    Ostman, J
    The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983 to 19982002In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 45, no 6, p. 783-791Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis. To analyse the incidence of Type I (insulin-dependent) diabetes mellitus in the 0-34 years age group in Sweden 1983-1998. Methods. Incidence and cumulative incidence per 100 000 and Poisson regression analysis of age-period effects was carried out using 11 751 cases from two nation-wide prospective registers. Results. Incidence (95%-CI) was 21.4 (20.8-21.9) in men and 17.1 (16.6-17.5) in women between 0 and 34 years of age. In boys aged 0-14 and girls aged 0-12 years the incidence increased over time, but it tended to decrease at older age groups, especially in men. Average cumulative incidence at 35 years was 748 in men and 598 in women. Cumulative incidence in men was rather stable during four 4-year periods (736, 732, 762, 756), while in women it varied more (592, 542, 617, 631). In males aged 0-34 years, the incidence did not vary between the 4-year periods (p=0.63), but time changes among the 3-year age groups differed (p<0.001). In females the incidence between the periods varied (p<0.001), being lower in 1987-1990 compared to 1983-1986, but time changes in the age groups did not differ (p=0.08). For both sexes median age at diagnosis was higher in 1983-1986 than in 1995-1998 (p<0.001) (15.0 and 12.5 years in males, 11.9 and 10.4 in females, respectively). Conclusion/interpretation. During a 16-year period the incidence of Type I diabetes did not increase in the 0-34 years age group in Sweden, while median age at diagnosis decreased. A shift to younger age at diagnosis seems to explain the increasing incidence of childhood Type I diabetes.

  • 252.
    Rajani, Rupesh
    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 Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Budd-Chiaris Syndrom2007Other (Other (popular science, discussion, etc.))
    Abstract [en]

          

  • 253.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    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.
    Letter: Incidence and prevalence rates in Budd-Chiari syndrome2009In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 58, no 6, p. 889-Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    [No abstract available]

  • 254.
    Rajani, Rupesh
    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 Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Portavenstrombos2007Other (Other (popular science, discussion, etc.))
    Abstract [sv]

    Portaventrombos (PVT) är ett ovanligt tillstånd. Bakomliggande orsaker är vanligen leversjukdom (framförallt cirros), intraabdominell malignitet samt hyperkoagulabilitet. Två eller flera samtidiga riskfaktorer, oftast en lokal faktor kombinerat med en systemisk, förekommer i mer än hälften av fallen. Man bör ha diagnosen i åtanke vid oklar buksmärta, vid tecken på portal hypertension utan samtidig leversjukdom samt vid plötslig försämring hos en patient med känd leversjukdom. Asymtomatiska patienter är inte ovanliga. Randomiserade behandlingsstudier saknas. Behandlingen inriktas på att reversera och förhindra progression av trombosen samt att förebygga och behandla komplikationer såsom varixblödningar och kolangiopati. Rekanalisering kan ske i upptill 90% av fallen vid tidigt insättande av antikoagulantia. Prognosen är god om patienten inte har cirros, malignitet eller mesenterialventrombos; 1-, 5- och 10-års överlevnad är då på 95%, 89% och 81%.

  • 255.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Bergquist, Annika
    Karolinska University Hospital.
    Melin, Tor
    Lund University Hospital.
    Friis-Liby, Ingalill
    Sahlgrens University Hospital.
    Kapraali, Marjo
    Danderyd Hospital.
    Werner, Marten
    Umea University Hospital.
    Sangfelt, Per
    Uppsala University.
    Wallerstedt, Sven
    Ostra Hospital, Gothenburg.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    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.
    INCREASED FACTOR VIII ACTIVITY IN PORTAL VEIN THROMBOSIS AND BUDD-CHIARI SYNDROME in HEPATOLOGY, vol 52, issue 4, pp 912A-912A2010In: HEPATOLOGY, John Wiley andamp; Sons, Ltd , 2010, Vol. 52, no 4, p. 912A-912AConference paper (Refereed)
    Abstract [en]

    n/a

  • 256.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Björnsson, E
    Sahlgrenska University Hospital, Göteborg.
    Bergquist, A
    Karolinska University Hospital, Stockholm.
    Danielsson, A
    Umeå University Hospital, Umeå.
    Gustavsson, A
    Örebro University Hospital.
    Grip, O
    Malmö University Hospital, Malmö.
    Melin, T
    Lund University Hospital, Lund.
    Sangfelt, P
    Uppsala University Hospital. Uppsala.
    Wallerstedt, S
    Östra Hospital, Göteborg.
    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.
    The epidemiology and clinical features of portal vein thrombosis: a multicentre study2010In: ALIMENTARY PHARMACOLOGY and THERAPEUTICS, ISSN 0269-2813, Vol. 32, no 9, p. 1154-1162Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Reliable epidemiological data for portal vein thrombosis are lacking.

    AIMS: To investigate the incidence, prevalence and survival rates for patients with portal vein thrombosis.

    METHODS: Retrospective multicentre study of all patients registered with the diagnosis of portal vein thrombosis between 1995 and 2004.

    RESULTS: A total of 173 patients (median age 57 years, 93 men) with portal vein thrombosis were identified and followed up for a median of 2.5 years (range 0-9.7). The mean age-standardized incidence and prevalence rates were 0.7 per 100,000 per year and 3.7 per 100,000 inhabitants, respectively. Liver disease was present in 70 patients (40%), malignancy in 27%, thrombophilic factors in 22% and myeloproliferative disorders in 11%. Two or more risk factors were identified in 80 patients (46%). At diagnosis, 65% were put on anticoagulant therapy. Thrombolysis, TIPS, surgical shunting and liver transplantation were performed in 6, 3, 2 and 8 patients, respectively. The overall survival at 1 year and 5 years was 69% and 54%. In the absence of malignancy and cirrhosis, the survival was 92% and 76%, respectively.

    CONCLUSIONS: The incidence and prevalence rates of portal vein thrombosis were 0.7 per 100,000 inhabitants per year and 3.7 per 100,000 inhabitants, respectively. Concurrent prothrombotic risk factors are common. The prognosis is variable and highly dependent on underlying disease.

  • 257.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Haglund, Sofie
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Bergquist, Annika
    Department of Gastroenterology & Hepatology, Karolinska University Hospital, Stockholm.
    Melin, Tor
    Division of Gastroenterology & Hepatology, University Hospital, Lund.
    Friis-Liby, Ingalill
    Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Verbaan, Hans
    Department of Medicine, University Hospital, Malmö.
    Kapraali, Marjo
    Karolinska Institutet, Department of Clinical Sciences Danderyd Hospital, Division of Medicine, Stockholm.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    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.
    High prevalence of the germline JAK2 46/1 haplotype and V617-mutationin Swedish patients with Budd-Chiari syndrome and Portal Vein Thrombosis2010Manuscript (preprint) (Other academic)
    Abstract [en]

    Background & Aims: To determine the prevalence of the somatic JAK2 V617F mutation and distribution of the germline JAK2 46/1 haplotype in Budd-Chiari Syndrome (BCS) and portal vein thrombosis (PVT).

    Methods: Real-time PCR was performed to genotype for the JAK2V 617F mutation and the 46/1 haplotype (tag-SNPs rs12343867, T>C and rs12340895, C>G) in blood samples of 19 BCS and 91 PVT patients (without intra-abdominal malignancy), and 283 controls from a background population.

    Results: The prevalence of JAK2 V617F-mutation was 63% in BCS and 14% in PVT patients. 10% in BCS and 2% in PVT had V617F negative MPD. Conversely, V617F positive subjects without known MPD was found in 5% of the BCS and in 1% of PVT patients. The frequency of the JAK2 46/1 haplotype was significantly higher in BCS (53%) and PVT (36%) patients compared to controls (27%) (p=0.02; OR=3.0; 95% CI 1.5-5.9 and OR=1.51; 95% CI 1.1-2.1, respectively). In PVT patients the JAK2 haplotype was highly enriched in non-cirrhotic patients (41%) (p <0.01 ; OR=1.8; 95% CI 1.2-2.6) but not in cirrhotic patients (23%) (p=0.53 ; OR= 0.8; 95% CI 0.4-1.7). An increased JAK2 46/1 haplotype frequency was evident only in V617F mutation positive patients.

    Conclusions: The prevalence of JAK2 V617F was high in BCS (63%) and non-cirrhotic PVT (14%), facilitating detection of latent MPD. A negative result dose not rule out MPD. The occurrence of the JAK2 46/1 haplotype was significantly higher in V617F mutation positive patients but not in mutation negative patients, suggesting that the haplotype may not have an independent role separated from the V617F mutation in BCS and PVT patients.

  • 258.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jennersjö, Cecilia
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care.
    Bergquist, Annika
    Department of Gastroenterology & Hepatology, Karolinska University Hospital, Stockholm.
    Melin, Tor
    Division of Gastroenterology & Hepatology, University Hospital, Lund.
    Friis-Liby, Ingalill
    Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Kapraali, Marjo
    Karolinska Institutet, Department of Clinical Sciences Danderyd Hospital, Division of Medicine, Stockholm.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology 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.
    Increased Factor VIII Activity in Portal Vein Thrombosis and Budd-Chiari Syndrome2010Manuscript (preprint) (Other academic)
    Abstract [en]

    n/a

  • 259.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Melin, Tor
    University Hospital, Lund .
    Bjornsson, Einar
    Sahlgrenska University Hospital, Göteborg.
    Broome, Ulrika
    Karolinska University Hospital, Stockholm.
    Sangfelt, Per
    University Uppsala Hospital, Uppsala.
    Danielsson, Ake
    Umea University Hospital, Umeå.
    Gustavsson, Anders
    University Hospital, Örebro.
    Grip, Olof
    Malmö University Hospital, Malmö.
    Svensson, Hans
    Vrinnevi Hospital, Norrköping.
    Loof, Lars
    Västerås City Hospital, Västerås.
    Wallerstedt, Sven
    Östra Hospital, Gothenberg.
    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.
    Budd-Chiari syndrome in Sweden: epidemiology, clinical characteristics and survival - an 18-year experience2009In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 29, no 2, p. 253-259Article in journal (Refereed)
    Abstract [en]

    The exact incidence and prevalence of Budd-Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival.

    To investigate the epidemiology, clinical presentation and survival in patients with BCS.

    Retrospective multicentre study in Sweden reviewing the medical records of all patients with BCS 1986-2003, identified from the computerised diagnosis database of 11 hospitals, including all university hospitals and liver transplantation centres.

    Forty-three patients with BCS were identified, of whom nine (21%) had concomitant portal vein thrombosis. The mean age-standardised incidence and prevalence rates in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. Myeloproliferative disorders (38%), thrombophilic factors (31%) and oral contraceptives (30%) were common aetiological factors. Two or more risk factors were present in 44%. In 23%, no risk factor was evident. The median follow-up time was 2.7 years. Seventy-two percent were on anticoagulant therapy during follow-up. Transjugular intrahepatic portosystemic shunting, surgical shunting procedures and liver transplantation were performed in 4, 6 and 18 patients respectively. Nineteen patients died. The overall transplantation-free survival at 1, 5 and 10 years was 47, 28 and 17% respectively.

    Budd-Chiari syndrome is a rare disorder; the mean age-standardised incidence and prevalence rates in Sweden in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. The presence of a myeloproliferative disorder was a common aetiological factor in our cohort and about half of the patients had a multifactorial aetiology. The transplantation-free survival was poor.

  • 260.
    Ratziu, V
    et al.
    Université Pierre et Marie Curie.
    Bugianesi, E
    University of Torino.
    Dixon, J
    Alfred Hospital.
    Fassio, E
    Hospital Nacional Profesor Alejandro Posadas.
    Ekstedt, Mattias
    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.
    Charlotte, F
    Université Pierre et Marie Curie.
    Kechagias, Stergios
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Poynard, T
    Université Pierre et Marie Curie.
    Olsson, R
    Sahlgrenska University Hospital.
    Histological progress of non-alcoholic fatty liver disease: a critical reassessment based on liver sampling variability.2007In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 26, p. 821-830Article in journal (Refereed)
    Abstract [en]

      Background: In non-alcoholic fatty liver disease, histological lesions display a significant sampling variability that is ignored when interpreting histological progression during natural history or therapeutic interventions. Aim: To provide a method taking into account sampling variability when interpreting crude histological data, and to investigate how this alters the conclusions of available studies. Methods: Natural history studies detailing histological progression and therapeutic trials were compared with the results of a previously published sampling variability study. Results: Natural history studies showed an improvement in steatosis, which was significantly higher than expected from sampling variability (47% vs. 8%, P < 0.0001). In contrast, no study showed a change in activity grade or ballooning higher than that of sampling variability. There was only a marginal effect on fibrosis with no convincing demonstration of a worsening of fibrosis, a conclusion contrary to what individual studies have claimed. Some insulin sensitizing drugs and anti-obesity surgery significantly improved steatosis, while most did not significantly impact on fibrosis or activity. Conclusions: Sampling variability of liver biopsy is an overlooked confounding factor that should be considered systematically when interpreting histological progression in patients with non-alcoholic fatty liver disease.

  • 261.
    Rauma, Jussi
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Spångéus, Anna
    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.
    El-Salhy, Magdy
    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.
    Ghrelin cell density in the gastrointestinal tracts of animal models of human diabetes.2006In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 21, no 1, p. 1-5Article in journal (Refereed)
    Abstract [en]

    Ghrelin cell density in the gastrointestinal tract of animal models of human diabetes type 1 and 2 was investigated. The animals used were non-obese diabetic (NOD) mice and obese diabetic mice. Ghrelin cells were detected by immunohistochemistry and quantified by computerized image analysis. Ghrelin-immunoreactive cells were detected in all animals studied. They were abundant in the oxyntic mucosa, patchy and few in the duodenum and rare in the colon. The density of ghrelin-immunoreactive cells decreased in diabetic, pre-diabetic NOD mice and in obese diabetic mice as compared to controls, though not statistically significant. It was concluded that the reduced density of ghrelin-immunoreactive cells in animal models of human diabetes type 1 and 2 might explain the slow gastric emptying and slow intestinal transit found in diabetes gastroenteropathy.

  • 262.
    Redéen, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Petersson, Fredrik
    National University Health System, Singapore.
    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.
    Mårdh, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Natural history of chronic gastritis in a population-based cohort2010In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 45, no 5, p. 540-549Article in journal (Refereed)
    Abstract [en]

    Objective. To describe and explore the natural history of Helicobacter pylori infection and chronic gastritis in terms of gastric mucosal atrophy and ulcer development over time in a population-based cohort. Material and methods. A population-based cohort of 314 volunteers was re-screened (median follow-up interval of 8.4 years) with gastroduodenoscopy with biopsy, assessment of H. pylori status, analysis of pepsinogens, and monitoring of a nonsteroidal anti-inflammatory drug (NSAID) use and alcohol and smoking habits. Results. The incidence of duodenal or prepyloric ulcer was 0.45 per 100 person years and was associated with weekly NSAID use (odds ratios, OR 27.8), weekly alcohol consumption (OR 19.4) and smoking (OR 31.0), but not with H. pylori status. De novo infection with H. pylori was not observed, and the infection had disappeared in 11 of 113 subjects. Among subjects with chronic gastritis, the incidence of atrophy of the corpus mucosa was 1.4 per 100 person years. Atrophy development was related to age (OR 1.23) and to the severity of chronic inflammation in the corpus mucosa at baseline (OR 8.98). Substituting atrophy for subnormal S-pepsinogen I/S-pepsingen II gave similar results. Conclusions. In this cohort, the minimum incidence of ulcer was 0.45 per 100 person years. Smoking, alcohol, and NSAIDs, but not H. pylori infection were significant risk factors. The incidence of atrophy of the corpus mucosa was 1.4 per 100 person years with a positive relation to age and to the degree of chronic inflammation at baseline. Atrophy was stationary in advanced stages.

  • 263.
    Sauma, Lilian
    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.
    Transcriptional activity of PPARγ in primary human adipocytes2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The prevalence of obesity is increasing in most parts of the world and is a strong risk factor for the development of insulin resistance, type 2 diabetes and hypertension. Adipose tissue is mainly composed of adipocytes which store energy in the form of triglycerides and release it as free fatty acids. Adipose tissue is one of the major regulators of energy homeostasis in the body. Adipose tissue in different regions of the body has different characteristics and adipocytes in intra-abdominal fat depots are more associated with insulin resistance than adipocytes from subcutaneous fat depots.

    Research performed during the past several years has led to an explosion in the understanding of adipose tissue and the active role that it plays in aspects of physiology and pathophysiology. One important discovery has been identification of the nuclear hormone receptor called peroxisome proliferator-activated receptor γ (PPARγ). Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor, which is highly expressed in adipocytes. PPARγ has been shown to affect several genes of importance for lipid metabolism, differentiation of fat cells and insulin sensitivity. The PPARγ receptor can be activated by thiazolidinediones (TZD), a class of insulinsensitising drugs, which promote fatty acid storage in fat depots and decrease glucose levels in plasma, thus, demonstrating the importance of PPARγ activity in insulin resistance and metabolic syndrome.

    This thesis has investigated the transcriptional activity of PPARγ in a clinically relevant cell type for insulin resistance and type 2 diabetes; the primary human adipocyte. For this purpose, a method for transfection of primary human adipocytes by electroporation and for measurement of the activity of PPARγ has been developed and optimised. This method has been used to study the effect of saturated and unsaturated fatty acids on the transcriptional activity of PPARγ. Interestingly, it was been found that saturated fatty acids can activate PPARγ, thus promoting a protection against diabetes. The strongest activator was the monounsaturated palmitoleic acid. The transcriptional activity of PPARγ in primary human adipocytes from intra-abdominal and subcutaneous adipose tissues was also examined. It was found that PPARγ activity is considerably lower in adipocytes from visceral compared with subcutaneous fat from the same subject. Another reason for using human tissue to reach clinical relevance shown here was that the same difference in PPARγ activity could not be found between intra-abdominal and subcutaneous fat tissues in mice. This finding may serve as the basis of why excess intraabdominal fat tissue is associated with high risk for development of type 2 diabetes and cardiovascular diseases.

    The blood pressure regulating renin-angiotensin system (RAS) in human adipose tissue and in isolated adipocytes was examined and related to PPARγ. It was found that the production of angiotensin II, which is an important hormone for increasing the blood pressure, can be produced by isolated adipocytes and that the production is higher in adipocytes coming from omental than subcutaneous fat tissue. Further, it was shown that angiotensin II inhibits PPARγ activity in omental adipocytes, thus reducing the insulin sensitivity. Therefore, this study connects two of the major risk factors in obesity; diabetes and hypertension, and may also explain how drugs, which inhibit the RAS, can also be protective against diabetes. In conclusion, the findings in this thesis give new knowledge about regulating mechanisms of fat cells and its importance in diabetes and cardiovascular disease.

    List of papers
    1. Expression of a mutant IRS inhibits metabolic and mitogenic signalling of insulin in human adipocytes
    Open this publication in new window or tab >>Expression of a mutant IRS inhibits metabolic and mitogenic signalling of insulin in human adipocytes
    Show others...
    2004 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, Vol. 221, no 1-2, p. 1-8Article in journal (Refereed) Published
    Abstract [en]

    Adipose tissue is a primary target of insulin, but knowledge about insulin signalling in human adipocytes is limited. We developed an electroporation technique for transfection of primary human adipocytes with a transfection efficiency of 15% ± 5 (mean ± S.D.). Human adipocytes were co-transfected with a mutant of IRS-3 (all four potential PI3-kinase binding motifs mutated: IRS-3F4) and HA-tagged protein kinase B (HA-PKB/Akt). HA-PKB/Akt was immunoprecipitated from cell lysates with anti-HA antibodies, resolved with SDS-PAGE, and immunoblotted with phospho-specific antibodies. We found that IRS-3F4 blocked insulin stimulation of HA-PKB/Akt phosphorylation and in further analyses also translocation of recombinant HA-tagged glucose transporter to the plasma membrane. IRS-3F4 also blocked insulin-induced activation of the transcription factor Elk-1. Our results demonstrate the critical importance of IRS for metabolic as well as mitogenic signalling by insulin. This method for transfection of primary human adipocytes will be useful for studying insulin signalling in human adipocytes with molecular biological techniques.

    Keywords
    Insulin, Transfection, Human, Adipocytes, Protein kinase B, Elk-1
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14538 (URN)10.1016/j.mce.2004.04.011 (DOI)000222854100001 ()
    Available from: 2007-06-01 Created: 2007-06-01 Last updated: 2019-06-28Bibliographically approved
    2. PPAR-gamma response element activity in intact primary human adipocytes: effects of fatty acids
    Open this publication in new window or tab >>PPAR-gamma response element activity in intact primary human adipocytes: effects of fatty acids
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    2006 (English)In: Nutrition (Burbank, Los Angeles County, Calif.), ISSN 0899-9007, E-ISSN 1873-1244, Vol. 22, no 1, p. 60-68Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: We studied the activity and regulation of the peroxisome proliferator-activated receptor-gamma response element (PPRE) in primary human adipocytes.

    METHODS: We transfected primary human adipocytes with a plasmid-encoding firefly luciferase cDNA under control of a PPRE from the acyl-coenzyme A oxidase gene by using our newly developed electroporation-based method. Several fatty acids were added to the fat cells to study potential activation of peroxisome proliferator-activated receptor-gamma.

    RESULTS: Cells responded maximally to 5 microM of rosiglitazone at a 5.1 +/- 1.4-fold over basal increase in luciferase activity. There was a positive correlation between body mass index and the response to 5 microM of rosiglitazone (r = 0.36, P = 0.03). Patients with type 2 diabetes had similar basal PPRE activity but responded more strongly to 5 microM of rosiglitazone than did non-diabetic subjects (10.2 +/- 5-fold and 5.4 +/- 1-fold over basal increase, respectively, P < 0.0001). Among saturated fatty acids, lauric acid was without effect, but 10 microM of palmitic or stearic acid increased PPRE activity 20% to 35% above basal levels. Monounsaturated palmitoleic acid at 1 microM induced a PPRE transcriptional activity that corresponded to half the therapeutic levels of rosiglitazone.

    CONCLUSION: Adipocytes from obese subjects and patients with type 2 diabetes responded particularly strongly to the effect of rosiglitazone on PPRE. Because fatty acids in the diet can affect the transcriptional activity of peroxisome proliferator-activated receptor-gamma over decades, the stimulation induced by stearic and palmitoleic acids can affect insulin sensitivity and, hence, cardiovascular morbidity and mortality in humans.

    Keywords
    Human, Fat cells, Fatty acid, peroxisome proliferator-activated receptor-γ, Rosiglitazone
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19165 (URN)10.1016/j.nut.2005.04.011 (DOI)000235119500009 ()16226011 (PubMedID)
    Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2019-06-28Bibliographically approved
    3. Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes
    Open this publication in new window or tab >>Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes
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    2007 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 1, p. 195-201Article in journal (Refereed) Published
    Abstract [en]

    AIMS/HYPOTHESIS: The amount of visceral fat mass strongly relates to insulin resistance in humans. The transcription factor peroxisome proliferator activated receptor gamma (PPARG) is abundant in adipocytes and regulates genes of importance for insulin sensitivity. Our objective was to study PPARG activity in human visceral and subcutaneous adipocytes and to compare this with the most common model for human disease, the mouse.

    MATERIALS AND METHODS: We transfected primary human adipocytes with a plasmid encoding firefly luciferase controlled by PPARG response element (PPRE) from the acyl-CoA-oxidase gene and measured PPRE activity by emission of light. RESULTS: We found that PPRE activity was 6.6-fold higher (median) in adipocytes from subcutaneous than from omental fat from the same subjects (n = 23). The activity was also 6.2-fold higher in subcutaneous than in intra-abdominal fat cells when we used a PPARG ligand-binding domain-GAL4 fusion protein as reporter, demonstrating that the difference in PPRE activity was due to different levels of activity of the PPARG receptor in the two fat depots. Stimulation with 5 micromol/l rosiglitazone did not induce a PPRE activity in visceral adipocytes that was as high as basal levels in subcutaneous adipocytes. Interestingly, in mice of two different strains the PPRE activity was similar in visceral and subcutaneous fat cells.

    CONCLUSIONS/INTERPRETATION: We found considerably lower PPARG activity in visceral than in subcutaneous primary human adipocytes. Further studies of the molecular mechanisms behind this difference could lead to development of drugs that target the adverse effects of visceral obesity.

    Keywords
    x-ray, vibrational, spectrum, Hartree-Fock, static exchange, Franck-Condon
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18462 (URN)10.1007/s00125-006-0515-x (DOI)000243188000026 ()17106695 (PubMedID)
    Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2019-06-28Bibliographically approved
    4. Isolated primary human visceral fat cells release more angiotensin II than subcutaneous adipocytes
    Open this publication in new window or tab >>Isolated primary human visceral fat cells release more angiotensin II than subcutaneous adipocytes
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background. Visceral obesity relates strongly to the metabolic syndrome and hence to hypertension. Although a local renin-angiotensin-system (RAS) in fat tissue is known, very few studies have dealt with RAS in isolated primary human fat cells, in particular from the visceral compartment.

    Methods. Measurement of angiotensin II (Ang II) in medium from isolated primary human fat cells from visceral and subcutaneous adipose tissues and analyses of RAS-components in human fat cells and fat tissues.

    Results. Primary human fat cells from omental adipose tissue produced more Ang II than subcutaneous cells. Treatment with insulin did not affect Ang II production and body-massindex of the fat-donors was unrelated to Ang II production. The PPAR gamma agonist rosiglitazone inhibited Ang II production in both types of isolated fat cells while addition of the Ang II receptor antagonist eprosartan inhibited the production in only subcutaneous fat cells. Addition of 50 or 200 nM of Ang II inhibited the PPAR gamma response elementactivity (PPRE-activity) in visceral, but not in the subcutaneous adipocytes.

    Conclusions. Since high PPRE-activity induced by rosiglitazone inhibited the Ang II production, it is possible that reduced PPRE-activity in the visceral human fat cells, demonstrated by us earlier, can explain the comparatively high Ang II production in these cells. This could form the basis for a local paracrine viscous circle in visceral fat where low PPRE-activity increases Ang II production that is further enhanced by Ang II-mediated inhibition of PPRE-activity which ultimately leads to high concentrations of Ang II in human adipose tissue.

    Keywords
    Fat cells, angiotensin II, human, insulin, peroxisome proliferator activated receptor gamma
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19167 (URN)
    Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2019-06-28Bibliographically approved
  • 264.
    Sauma, Lilian
    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.
    Franck, Niclas
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Kjølhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine. 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.
    Isolated primary human visceral fat cells release more angiotensin II than subcutaneous adipocytesManuscript (preprint) (Other academic)
    Abstract [en]

    Background. Visceral obesity relates strongly to the metabolic syndrome and hence to hypertension. Although a local renin-angiotensin-system (RAS) in fat tissue is known, very few studies have dealt with RAS in isolated primary human fat cells, in particular from the visceral compartment.

    Methods. Measurement of angiotensin II (Ang II) in medium from isolated primary human fat cells from visceral and subcutaneous adipose tissues and analyses of RAS-components in human fat cells and fat tissues.

    Results. Primary human fat cells from omental adipose tissue produced more Ang II than subcutaneous cells. Treatment with insulin did not affect Ang II production and body-massindex of the fat-donors was unrelated to Ang II production. The PPAR gamma agonist rosiglitazone inhibited Ang II production in both types of isolated fat cells while addition of the Ang II receptor antagonist eprosartan inhibited the production in only subcutaneous fat cells. Addition of 50 or 200 nM of Ang II inhibited the PPAR gamma response elementactivity (PPRE-activity) in visceral, but not in the subcutaneous adipocytes.

    Conclusions. Since high PPRE-activity induced by rosiglitazone inhibited the Ang II production, it is possible that reduced PPRE-activity in the visceral human fat cells, demonstrated by us earlier, can explain the comparatively high Ang II production in these cells. This could form the basis for a local paracrine viscous circle in visceral fat where low PPRE-activity increases Ang II production that is further enhanced by Ang II-mediated inhibition of PPRE-activity which ultimately leads to high concentrations of Ang II in human adipose tissue.

  • 265.
    Sauma, Lilian
    et al.
    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.
    Franck, Niclas
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Paulsson, Johan F
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Westermark, Gunilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Kjølhede, Preben
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Söderström, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 1, p. 195-201Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The amount of visceral fat mass strongly relates to insulin resistance in humans. The transcription factor peroxisome proliferator activated receptor gamma (PPARG) is abundant in adipocytes and regulates genes of importance for insulin sensitivity. Our objective was to study PPARG activity in human visceral and subcutaneous adipocytes and to compare this with the most common model for human disease, the mouse.

    MATERIALS AND METHODS: We transfected primary human adipocytes with a plasmid encoding firefly luciferase controlled by PPARG response element (PPRE) from the acyl-CoA-oxidase gene and measured PPRE activity by emission of light. RESULTS: We found that PPRE activity was 6.6-fold higher (median) in adipocytes from subcutaneous than from omental fat from the same subjects (n = 23). The activity was also 6.2-fold higher in subcutaneous than in intra-abdominal fat cells when we used a PPARG ligand-binding domain-GAL4 fusion protein as reporter, demonstrating that the difference in PPRE activity was due to different levels of activity of the PPARG receptor in the two fat depots. Stimulation with 5 micromol/l rosiglitazone did not induce a PPRE activity in visceral adipocytes that was as high as basal levels in subcutaneous adipocytes. Interestingly, in mice of two different strains the PPRE activity was similar in visceral and subcutaneous fat cells.

    CONCLUSIONS/INTERPRETATION: We found considerably lower PPARG activity in visceral than in subcutaneous primary human adipocytes. Further studies of the molecular mechanisms behind this difference could lead to development of drugs that target the adverse effects of visceral obesity.

  • 266.
    Scholin, A
    et al.
    Uppsala University.
    Nystrom, L
    Umea 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.
    Bolinder, J
    Karolinska University.
    Bjork, E
    Uppsala University.
    Berne, C
    Uppsala University.
    A Karlsson, F
    Uppsala University.
    Proinsulin/C-peptide ratio, glucagon and remission in new-onset Type 1 diabetes mellitus in young adults2011In: DIABETIC MEDICINE, ISSN 0742-3071, Vol. 28, no 2, p. 156-161Article in journal (Refereed)
    Abstract [en]

    Pandgt;Aims After initiation of treatment in Type 1 diabetes, a period with lower insulin requirement often follows, reflecting increased insulin sensitivity and improved insulin secretion. We explored if efficiency of proinsulin processing is associated with the remission phenomenon. Methods Seventy-eight patients with new-onset Type 1 diabetes were followed prospectively for 3 years. Daily insulin dosage, HbA(1c), plasma glucose, proinsulin, C-peptide, glucagon concentrations and islet antibodies were determined at diagnosis and after 3, 6, 9, 12, 18, 24, 30 and 36 months. We studied remission, defined as an insulin dose andlt; 0.3 U kg-1 24 h-1 and HbA(1c) within the normal range, in relation to the above-mentioned variables. Results A rise and subsequent decline in plasma proinsulin and C-peptide concentrations was observed. Forty-five per cent of the patients experienced remission at one or more times, characterized by higher proinsulin and C-peptide levels, and lower proinsulin/C-peptide ratios, indicating more efficient proinsulin processing, compared with those not in remission. Non-remission also tended to be associated with higher glucagon values. Patients entering remission were more often men, had higher BMI at diagnosis, but did not differ at baseline with respect to islet antibody titres compared with patients with no remission. Conclusions Remissions after diagnosis of Type 1 diabetes were associated with lower proinsulin/C-peptide ratios, suggesting more efficient proinsulin processing, and tended to have lower glucagon release than non-remissions. This indicates that, in remission, the residual islets maintain a secretion of insulin and glucagon of benefit for control of hepatic glucose production.

  • 267. Schwartz, GG
    et al.
    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.
    Ezekowitz, MD
    Ganz, P
    Oliver, MF
    Waters, D
    Zeiher, A
    Chaitman, BR
    Atorvastatin for acute coronary syndromes2001In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 286, no 5, p. 533-533Other (Other academic)
  • 268. Schwartz, GG
    et al.
    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.
    Ezekowitz, MD
    Ganz, P
    Oliver, MF
    Waters, D
    Zeiher, A
    Chaitman, BR
    Atorvastatin for acute coronary syndromes - Reply2001In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 286, no 5, p. 533-534Other (Other academic)
  • 269.
    Schwartz, G.G.
    et al.
    Cardiology Section, VA Medical Center, Denver, CO, United States, University of Colorado Health Sciences Center, Denver, CO, United States, Denver VA Medical Center (111B), Denver, CO 80220, United States.
    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.
    Szarek, M.
    Pfizer, New York, NY, United States.
    Sasiela, W.J.
    Pfizer, New York, NY, United States.
    Relation of characteristics of metabolic syndrome to short-term prognosis and effects of intensive statin therapy after acute coronary syndrome: An analysis of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial2005In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 10, p. 2508-2513Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - We examined relations between characteristics of the metabolic syndrome, early cardiovascular risk, and effect of early, intensive statin therapy after acute coronary syndrome. RESEARCH DESIGN AND METHODS - A total of 3,038 patients in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial were characterized by the presence or absence of a history of diabetes, a history of hypertension and/or blood pressure =130/=85, BMI > 30 kg/m2, HDL cholesterol <40 mg/dl (men) or <50 mg/dl (women), and triglycerides =150 mg/dl. Patients with three or more of these characteristics were categorized as having metabolic syndrome. RESULTS - A total of 38% of patients (n = 1,161) met criteria for metabolic syndrome as defined in this study and had a 19% incidence of a primary end point event (death, nonfatal myocardial infarction, cardiac arrest, or recurrent unstable myocardial ischemia) during the 16-week trial. Patients with two or fewer characteristics (n = 1,877) were classified as not having metabolic syndrome and had a 14% incidence of a primary end point event. In univariate analysis, the individual characteristics that bore a significant relation to risk were diabetes and low HDL cholesterol. In a multivariable model including age, sex, and randomized treatment assignment, presence of metabolic syndrome was associated with a hazard ratio of 1.49 (95% Cl 1.24-1.79, P < 0.0001). Relative risk reduction with 80 mg atorvastatin daily compared with placebo was similar in patients with and without metabolic syndrome. CONCLUSIONS - Metabolic syndrome, as defined in the context of this clinical trial, is a strong predictor of early recurrent ischemic events after acute coronary syndrome. © 2005 by the American Diabetes Association.

  • 270. Schwartz, Gregory G
    et al.
    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.
    The case for intensive statin therapy after acute coronary syndromes2005In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 96, no 5 SUPPL.Article in journal (Refereed)
    Abstract [en]

    Acute coronary syndromes (ACS) consist of unstable angina or acute myocardial infarction and are associated with a high risk of early recurrent ischemic events. Revascularization procedures do not modify underlying pathophysiology and only modestly reduce early ischemic events after an index episode of ACS. Although statins improve dyslipidemia and cardiovascular risk over the long term, efforts to identify new ACS treatments are focusing on the ability of statins to modify the arterial wall-blood interface and reduce the risk of early recurrent ischemic events. Statins have been shown to reduce circulating markers of inflammation within days of an acute ischemic event. Short-term statin therapy also has been associated with improved coronary endothelial function, reversal of prothrombotic states, and reduction in atherosclerotic plaque volume. Findings from 6 randomized, controlled intervention trials were evaluated to determine if risk reduction is associated with the intensity of statin therapy. In addition, the predictive ability of baseline lipid levels and inflammatory markers were examined. High-intensity statin therapy (atorvastatin 80 mg) reduced early recurrent ischemic events after ACS compared with moderate-intensity treatment (eg, pravastatin 40 mg) or placebo. Moderate-intensity regimens (simvastatin 40 mg, pravastatin 20 to 40 mg, fluvastatin 80 mg, cerivastatin 0.4 mg) provided minimal benefit compared with placebo. Although there was no apparent relation between low-density lipoprotein (LDL) cholesterol levels before or during randomized treatment and short-term (4-month) risk of recurrent events, the degree of LDL cholesterol reduction with statin treatment after ACS may be related to longer-term event reduction. Moreover, evidence suggests that anti-inflammatory effects of high-intensity statin treatment are associated with clinical benefit. © 2005 Elsevier Inc. All rights reserved.

  • 271.
    Schwartz, Gregory G
    et al.
    VA Med Ctr, Cardiol Sect 111B, Denver, CO 80220 USA.
    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.
    Ballantyne, Christie M
    Baylor Coll Med, Houston, TX 77030 USA.
    Barter, Phillip J
    Heart Res Inst, Sydney, NSW, Australia.
    Holme, Ingar M
    Oslo Univ Hosp, Oslo, Norway.
    Kallend, David
    F Hoffmann La Roche and Co Ltd, CH-4002 Basel, Switzerland.
    Leiter, Lawrence A
    Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
    Leitersdorf, Eran
    Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel.
    McMurray, John J V
    Univ Glasgow, Cardiovasc Res Ctr, British Heart Fdn, Glasgow G12 8QQ, Lanark, Scotland.
    Shah, Prediman K
    Cedars-Sinai Medical Center, Los Angeles, CA.
    Tardif, Jean-Claude
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.
    Chaitman, Bernard R
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
    Duttlinger-Maddux, Regina
    F Hoffmann La Roche and Co Ltd, CH-4002 Basel, Switzerland.
    Mathieson, John
    F Hoffmann La Roche and Co Ltd, CH-4002 Basel, Switzerland.
    Rationale and design of the dal-OUTCOMES trial: Efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome2009In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 158, no 6, p. 896-U34Article in journal (Refereed)
    Abstract [en]

    Background Despite contemporary therapies for acute coronary syndrome (ACS), morbidity and mortality remain high. Low levels of high-density lipoprotein (HDL) cholesterol are common among patients with ACS and may contribute to ongoing risk. Strategies that raise levels of HDL cholesterol, such as inhibition of cholesterol ester transfer protein (CETP), might reduce risk after ACS. Dal-OUTCOMES is a multicenter, randomized, double-blind, placebo-controlled trial designed to test the hypothesis that CETP inhibition with dalcetrapib reduces cardiovascular morbidity and mortality in patients with recent ACS. Design The study will randomize approximately 15,600 patients to receive daily doses of dalcetrapib 600 mg or matching placebo, beginning 4 to 12 weeks after an index ACS event. There are no prespecified boundaries for HDL cholesterol levels at entry. Other elements of care, including management of low-density lipoprotein cholesterol, are to follow best evidence-based practice. The primary efficacy measure is time to first occurrence of coronary heart disease death, nonfatal acute myocardial infarction, unstable angina requiring hospital admission, resuscitated cardiac arrest, or atherothrombotic stroke. The trial will continue until 1,600 primary end point events have occurred, all evaluable subjects have been followed for at least 2 years, and 80% of evaluable subjects have been followed for at least 2.5 years. Summary Dal-OUTCOMES will determine whether CETP inhibition with dalcetrapib, added to current evidence-based care, reduces cardiovascular morbidity and mortality after ACS.

  • 272. Schölin, A
    et al.
    Björklund, L
    Borg, H
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Björk, E
    Blohmé, G
    Bolinder, J
    Eriksson, JW
    Gudbjörnsdottir, S
    Nyström, L
    Östman, J
    Karlsson, AF
    Sundkvist, G
    Islet antibodies and remaining β-cell function 8 years after diagnosis of diabetes in young adults: A prospective follow-up of the nationwide Diabetes Incidence Study in Sweden2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 255, no 3, p. 384-391Article in journal (Refereed)
    Abstract [en]

    Objectives. To establish the prevalence of remaining β-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. Design. Population-based cohort study. Setting. Nationwide from all Departments of Medicine and Endocrinology in Sweden. Subjects. A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. Main outcome measure. Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved β-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies -were measured. Results. Amongst 269 islet antibody positives (ab+) at diagnosis, preserved β-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2,respectively, P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively, P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively, P = 0.007) at diagnosis compared with ab+ without remaining β-cell function. Amongst the 241 patients without detectable β-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. Conclusions. Sixteen per cent of patients with autoimmune type 1 diabetes had remaining β-cell function 8 years after diagnosis whereas 5.8% with β-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.

  • 273. Schölin, A
    et al.
    Törn, C
    Nyström, L
    Berne, C
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Blohmé, G
    Bolinder, J
    Eriksson, JW
    Kockum, I
    Landin-Olsson, M
    Östman, J
    Karlsson, FA
    Sundkvist, G
    Björk, E
    Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in Type 1 diabetes2004In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 21, no 5, p. 447-455Article in journal (Refereed)
    Abstract [en]

    Aim: To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM). Methods: In Sweden, 362 patients (15-34 years), classified as Type 1 DM were included in a prospective, nation-wide population-based study. All patients were followed at local hospitals for examination of HbA1c and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose ≤ 0.3 U/kg/24 h and HbA1c within the normal range, was analysed in relation to characteristics at diagnosis. Results: Remissions were seen in 43% of the patients with a median duration of 8 months (range 1-73). Sixteen per cent had a remission with a duration > 12 months. Among patients with antibodies (ab+), bivariate analysis suggested that adult age, absence of low BMI, high plasma C-peptide concentrations, lack of ketonuria or ketoacidosis at diagnosis and low insulin dose at discharge from hospital were associated with a high possibility of achieving remission. Multiple regression showed that normal weight (BMI of 20-24.9 kg/m2) was the only factor that remained significant for the possibility of entering remission. In survival analysis among ab+ remitters, a low number of islet antibodies, one or two instead of three or four, were associated with a long duration of remissions. Conclusion: In islet antibody-positive Type 1 DM, normal body weight was the strongest factor for entering remission, whilst a low number of islet antibodies was of importance for the duration.

  • 274.
    Sjöblom, Peter
    et al.
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    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.
    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.
    Östgren, Carl Johan
    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.
    Microalbuminuria but not reduced GFR is a marker of subclinical atherosclerosis and arterial stiffness in type 2 diabetes in DIABETOLOGIA, vol 53, issue , pp2010In: DIABETOLOGIA, Springer Science Business Media , 2010, Vol. 53Conference paper (Refereed)
    Abstract [en]

    n/a

  • 275.
    Sjöblom, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Primary Health Care in Norrköping.
    Tengblad, Anders
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Löfgren, Ulla-Britt
    Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Lannering, Christina
    The Research and Development Department of Local Health Care, County Council of Jönköping, Jönköping, Sweden.
    Anderberg, Niklas
    Vråen Primary Health Care Centre, Värnamo, Sweden.
    Rosenqvist, Ulf
    Department of Internal Medicine, Motala Hospital, Motala, Sweden.
    Mölstad, Sigvard
    The Research and Development Department of Local Health Care, County Council of Jönköping, Jönköping, Sweden.
    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.
    Can diabetes medication be reduced in elderly patients?: An observational study of diabetes drug withdrawal in nursing home patients with tight glycaemic control2008In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 82, no 2, p. 197-202Article in journal (Refereed)
    Abstract [en]

    Aim: To explore the feasibility of withdrawal of diabetes medication in elderly patients with HbA1c £ 6.0%.

    Methods: HbA1c was measured in 98 patients with known diabetes in 17 nursing homes in Sweden. 32 subjects with HbA1c £ 6.0% participated in the drug withdrawal study. After measuring plasma glucose on three consecutive days, diabetes drugs were reduced, i.e. complete withdrawal of oral anti-diabetic drugs (OADs), complete insulin withdrawal when doses were £ 20 units/day and reduced by half in patients on more than 20 units/day.

    Results: We identified 31 episodes of plasma glucose £ 4.4 mmol/l, most of them nocturnal (n=17). Mean HbA1c was 5.2 % ± 0.4 compared to 7.1 % ± 1.6 in the non-intervention group. Three months after the diabetes drug discontinuation, 24 patients (75%) remained in the intervention group and mean HbA1c was then 5.8 %. ± 0.9. Six months after baseline investigation mean HbA1c in the intervention group was 5.8 % ± 1.1 compared with 6.6 % ± 1.4 in the non-intervention group.

    Conclusions: Hypoglycaemic events are common among elderly patients with type 2 diabetes. The withdrawal of diabetes medication in elderly with tight glycaemic control is safe and may decrease the risk for hypoglycaemia.

  • 276.
    Sjöstrand, M
    et al.
    RandD AstraZeneca.
    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.
    Eriksson, J W
    RandD AstraZeneca.
    Gudbjornsdottir, S
    Sahlgrenska University Hospital.
    Lindmark, S
    Umeå University.
    Landin-Olsson, M
    Lund University Hospital.
    Nyström, L
    Umeå University.
    Svensson, M K
    Sahlgrenska University Hospital.
    Adolfsson, P
    RandD AstraZeneca.
    Arneklev, K
    RandD AstraZeneca.
    Bolinder, J
    Karolinska University Hospital.
    Dynamic beta cell function in young type 2 diabetes patients (15-34 years) in the Diabetes Incidence Study in Sweden register in DIABETOLOGIA, vol 53, issue , pp2010In: DIABETOLOGIA, Springer Science Business Media , 2010, Vol. 53Conference paper (Refereed)
    Abstract [en]

    n/a

  • 277.
    Steen Carlsson, K
    et al.
    Malmö University Hospital.
    Landin-Olsson, M
    Lund University Hospital.
    Nystrom, L
    Umea 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.
    Bolinder, J
    Karolinska University Hospital.
    Ostman, J
    Karolinska University Hospital.
    Gudbjornsdottir, S
    Nordic School of Public Health, Gothenburg.
    Long-term detrimental consequences of the onset of type 1 diabetes on annual earnings-evidence from annual registry data in 1990-20052010In: DIABETOLOGIA, ISSN 0012-186X, Vol. 53, no 6, p. 1084-1092Article in journal (Refereed)
    Abstract [en]

    Young adults in the early stages of their participation in the labour market may be particularly vulnerable to the effects of onset of a chronic disease. Our aim was to quantify the consequences of the onset of type 1 diabetes in young adults on annual earnings, using individual-level longitudinal data before and after the onset of diabetes. The Econ-DISS database contains annual socioeconomic information for 1990-2005 from Statistics Sweden. Econ-DISS includes data for persons with diabetes onset at the age of 15-34 years between 1983 and 2005, registered in the national Diabetes Incidence Study in Sweden (DISS) database, and for controls. Considering the onset of type 1 diabetes as an unanticipated and significant life event, we compared the progression of annual earnings for 3,650 cases born between 1949 and 1970 before and after onset of diabetes with that of 14,629 controls. Possible confounders-education, participation in the labour market, sick leave and parental education-were analysed. We found no differences between the groups in annual earnings or participation in the labour market before onset of diabetes. After onset, persons with type 1 diabetes gradually lagged behind the controls. Their median annual earnings were lower in each year from 1995 to 2005 (p andlt; 0.01). The difference in 2005 was euro (EUR) 1,411 (5.3%). Controlling for confounders, duration of type 1 diabetes a parts per thousand yen10 years was associated with 4.2% (men) and 8.1% (women) lower average annual earnings for persons with upper secondary education only who were active in the labour market. The onset of type 1 diabetes in young adults has long-term detrimental consequences on earnings that cannot be attributed to confounders.

  • 278.
    Stenestrand, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of 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.
    Ju lägre LDL-kolesterol destö bättre!2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, p. 3246-3247Article in journal (Other academic)
  • 279.
    Stenestrand, Ulf
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Nystrom, 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.
    Association between admission supine systolic blood pressure and 1-year mortality in patients admitted to the intensive care unit for acute chest pain.2010In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 303, no 12, p. 1167-1172Article in journal (Refereed)
    Abstract [en]

    CONTEXT: High resting blood pressure (BP) is among the best studied and established risk factors for cardiovascular disease. However, little is known about the relationship between BP under acute stress, such as in acute chest pain, and subsequent mortality. OBJECTIVE: To study long-term mortality related to supine BP in patients admitted to the medical intensive care unit (ICU) for acute chest pain. DESIGN, SETTING, AND PARTICIPANTS: Data from the RIKS-HIA (Registry of Information and Knowledge About Swedish Heart Intensive Care Admissions) was used to analyze the mortality in relation to supine admission systolic BP in 119,151 participants who were treated at the ICU for the symptom of chest pain from 1997 through 2007. Results from this prospective cohort study were presented according to systolic BP quartiles: Q1, less than 128 mm Hg; Q2, from 128 to 144 mm Hg; Q3, from 145 to 162 mm Hg; and Q4, at or above 163 mm Hg. MAIN OUTCOME MEASURE: Total mortality. RESULTS: Mean (SD) follow-up time was 2.47 (1.5) years (range, 1-10 years). One-year mortality rate by Cox proportional hazard model (adjusted for age, sex, smoking, diastolic BP, use of antihypertensive medication at admission and discharge, and use of lipid-lowering and antiplatelet medication at discharge) showed that participants in Q4 had the best prognosis (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.72-0.80, Q4 compared with Q2; corresponding risks for Q1 were HR, 1.46; 95% CI, 1.39-1.52, and for Q3, HR, 0.83; 95% CI, 0.79-0.87). Patients in Q4 had a 21.7% lower absolute risk compared with Q2, patients in Q3 had a 15.2% lower risk than in Q2, and patients in Q1 had a 40.3% higher risk for mortality than in Q2. The worse prognosis in Q2 compared with Q4 was independent of body mass index and previous diagnoses and similar when analysis was restricted to patients with a final diagnosis of angina or myocardial infarction (HR, 0.75; 95% CI, 0.71-0.80, Q4 compared with Q2). CONCLUSION: Among patients admitted to the ICU for chest pain, there is an inverse association between admission supine systolic BP and 1-year mortality rate.

  • 280.
    Stenkula, Karin G.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Said Suma, Lilian
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, Margareta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Thorn, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Gustavsson, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Söderström, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    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.
    Expression of a mutant IRS inhibits metabolic and mitogenic signalling of insulin in human adipocytes2004In: Molecular and Cellular Endocrinology, ISSN 0303-7207, Vol. 221, no 1-2, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Adipose tissue is a primary target of insulin, but knowledge about insulin signalling in human adipocytes is limited. We developed an electroporation technique for transfection of primary human adipocytes with a transfection efficiency of 15% ± 5 (mean ± S.D.). Human adipocytes were co-transfected with a mutant of IRS-3 (all four potential PI3-kinase binding motifs mutated: IRS-3F4) and HA-tagged protein kinase B (HA-PKB/Akt). HA-PKB/Akt was immunoprecipitated from cell lysates with anti-HA antibodies, resolved with SDS-PAGE, and immunoblotted with phospho-specific antibodies. We found that IRS-3F4 blocked insulin stimulation of HA-PKB/Akt phosphorylation and in further analyses also translocation of recombinant HA-tagged glucose transporter to the plasma membrane. IRS-3F4 also blocked insulin-induced activation of the transcription factor Elk-1. Our results demonstrate the critical importance of IRS for metabolic as well as mitogenic signalling by insulin. This method for transfection of primary human adipocytes will be useful for studying insulin signalling in human adipocytes with molecular biological techniques.

  • 281.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Grännö, Christer
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Bodemar, Göran
    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.
    Järnerot, Ggunnar
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ockander, Leif
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Tysk, Curt
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Blomberg, Björn
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    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.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    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.
    Evaluation of the Inflammatory Bowel Disease Questionnaire in Swedish patients with Crohn's disease2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 8, p. 934-943Article in journal (Refereed)
    Abstract [en]

    Objective. Health-related quality of life (HRQoL) is an important measure of inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the validity, reliability and responsiveness of the Swedish translation of the IBDQ in patients with Crohn's disease (CD). Material and methods. Four hundred and forty-eight patients with CD completed the IBDQ and three other HRQoL questionnaires (Rating Form of IBD Patient Concerns, Short Form-36, and the Psychological General Well-Being Index) in connection with their regular visit at the outpatient clinic. Disease activity was assessed by the physician on a 4-point Likert scale. Thirty-two patients who were stable in remission completed the questionnaires a second time, 4 weeks later. A total of 418 patients repeated all measurements after 6 months. Results. The dimensional scores were highly correlated with other measures of corresponding aspects of HRQoL and were significantly better in remission than in relapse. High test-retest correlations indicated good reliability. Responsiveness was confirmed in patients whose disease activity changed over time. However, high correlations between the dimensions, poor correlations between items within each dimension, and factor analysis all indicated that the original grouping of the items is not valid for Swedish CD patients. Conclusions. Although the Swedish IBDQ has good external validity, reliability and responsiveness for patients with CD, our results did not support the original grouping of the items. © 2006 Taylor & Francis.

  • 282.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Grännö, Christer
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Järnerot, Gunnar
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ockander, Leif
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Tysk, Curt
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden, Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Blomberg, Björn
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, 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.
    Hjortswang, Henrik
    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.
    Short health scale: A valid, reliable, and responsive instrument for subjective health assessment in Crohn's disease2008In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 1, p. 47-52Article in journal (Refereed)
    Abstract [en]

    Background: Health-related quality of life (HRQoL) is an essential part of inflammatory bowel disease (IBD) assessment. The Short Health Scale (SHS), an HRQoL questionnaire in which the patients rate the disease impact on 4 important aspects of subjective health (symptoms, function, worry, and general well-being) was demonstrated in a previous study to be valid, reliable, and responsive in patients with ulcerative colitis. The present study evaluates the SHS in patients with Crohn's disease (CD). Methods: In all, 367 CD patients completed the SHS and 4 other HRQoL questionnaires (IBDQ, SF-36, RFIPC, and PGWB) at their regular outpatient visits. Then 330 patients completed the questionnaires at a second visit 6 months later. In addition, reliability data were obtained from repeat measurements 4 weeks after the first visit in 40 patients stable in remission. Results: Patients in remission scored better on all 4 questions than those with active disease (P < 0.001). All 4 questions were strongly correlated with the corresponding dimensions of the other HRQoL questionnaires (rS = 0.74-0.83). Reliability was confirmed with strong test-retest correlations (rS = 0.69-0.82) and intraclass correlation coefficients (0.66-0.77). Patients who changed from remission to active disease or vice versa showed a significant change in all 4 SHS scores (P < 0.005). Conclusions: SHS is a valid, reliable and responsive HRQoL instrument also in patients with CD. It is easily completed by the patient and requires no further calculation by the investigator. SHS gives a comprehensive overview of the main aspects of the patient's subjective health perception and is a useful tool in both clinical practice and clinical studies. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

  • 283.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Tysk, Curt
    Orebro Univ Hosp, Dept Med, Div Gastroenterol, Orebro, Sweden.
    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.
    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.
    Hjortswang, Henrik
    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.
    Factors Predicting the Outcome of Disease Activity Assessment in Crohns Disease2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1859-1866Article in journal (Refereed)
    Abstract [en]

    Background: The Crohns Disease Activity Index (CDAI) has become the gold standard for assessment of disease activity in CD. This study investigated the relationship between CDAI and the physicians global assessment of disease activity (PGA) and whether different demographic and disease-related factors predict the outcome. Methods: Multiple linear regression analysis was used to investigate the relationship between CDAI and PGA obtained from 405 CD patients. Predictors of the CDAI and the PGA outcome were identified. Results: The correlation between CDAI and PGA was moderate. In patients with CDAI greater than 150, 72% of the total score were derived froth the subjective variables. The regression coefficients were not significant for 3 of the CDAI variables. In regression analysis, C-reactive protein (CRP), stenosis, smoking, bowel resection, concomitant disease, and gender predicted the CDAI outcome. The PGA outcome was predicted only by CRP, stenosis, and fistula. Conclusions: The correlation between CDAI and PGA was moderate and the subjective variables had a high impact on CDAI. Factors with no obvious relation to inflammatory activity predicted the outcome of CDAI, but not PGA. In trials of CD therapies, separation of subjective (symptoms, well-being) from objective (endoscopy, inflammatory markers) variables should be considered in the assessment of disease activity.

  • 284.
    Stjernman, Henrik
    et al.
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Tysk, Curt
    Örebro University Hospital, Sweden.
    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.
    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.
    Hjortswang, Henrik
    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.
    Worries and concerns in a large unselected cohort of patients with Crohns disease2010In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 6, p. 696-706Article in journal (Refereed)
    Abstract [en]

    Objective. Disease-related worries constitute an important dimension of patient-reported perception of health status in inflammatory bowel disease (IBD). The Rating Form of IBD Patient Concerns (RFIPC) questionnaire is purported to measure IBD-related worries. This study evaluated the psychometric properties of a Swedish translation of RFIPC in an unselected population of Crohns disease (CD) patients. The degree and nature of the worries were characterized and predictive factors for outcome of RFIPC and underlying dimensions were identified. Material and Methods. The RFIPC was completed by 447 CD patients in conjunction with regular visits. A physician global assessment of disease activity and four other health-related quality of life (HRQL) questionnaires were used for construct validity. Reliability and responsiveness were evaluated with follow-up visits. Underlying dimension and predictive factors were identified with factor analysis and multiple linear regression analysis. Results. Test-retest reliability was 0.90, correlation with corresponding HRQL measures 0.60-0.80 and responsiveness ratio 0.84. Median RFIPC sum score was lower than in previous studies. Top three concerns were ostomy, energy level and bowel control. Four dimensions were identified in descending order of concern: disease-related complications, daily-life achievements, intimacy, and stigmatization. Predictors of RFIPC score were disease activity, gender, and BMI (p andlt; 0.001-0.008). Conclusions. The Swedish version of RFIPC exhibited an adequate psychometric performance in CD patients, but was less sensitive to change in disease activity. The patients were more concerned about complications and achievement than intimacy and stigmatization. The strongest predictors of more worry were active disease, female gender and higher BMI.

  • 285.
    Strandberg, Timo E
    et al.
    University of Oulu.
    Holme, Ingar
    Ullevaal University Hospital.
    Faergeman, Ole
    Arhus University Hospital.
    Kastelein, John J P
    University of Amsterdam.
    Lindahl, Christina
    Pfizer Swedeb.
    Lytken Larsen, Mogens
    Arhus University 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.
    Pedersen, Terje R
    Ullevaal University Hospital.
    J Tikkanen, Matti
    Comparative Effect of Atorvastatin (80 mg) Versus Simvastatin (20 to 40 mg) in Preventing Hospitalizations for Heart Failure in Patients With Previous Myocardial Infarction2009In: AMERICAN JOURNAL OF CARDIOLOGY, ISSN 0002-9149, Vol. 103, no 10, p. 1381-1385Article in journal (Refereed)
    Abstract [en]

    We investigated whether intensive cholesterol lowering could more effectively prevent heart failure (HF) in secondary prevention. The IDEAL study was a 4.8-year prospective, randomized trial comparing "usual" simvastatin treatment (20 to 40 mg/day, n = 4,449) with high-dose atorvastatin (80 mg/day, n = 4,439) in patients with a history of myocardial infarction (MI). At baseline, 94% of patients (n = 8,351) had no history of HF. During the course of the trial, there were 222 new or recurrent hospitalizations for HF (57 and 165 in those with and without HF at baseline, respectively), 123 (2.8%) in the simvastatin group and 99 (2.2%) in the atorvastatin group (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.62 to 1.05, p = 0.11). After adjustments, atorvastatin 80 mg was associated with a 26% decrease of new HF events compared with simvastatin 20 to 40 mg (HR 0.74, 95% CI 0.57 to 0.97, p = 0.03). Atorvastatin tended to be associated with fewer HF events in those with HF at baseline (n = 537, HR 0.65, 95% CI 0.38 to 1.11, p = 0.11) and those without HF at baseline (n = 8,351, HR 0.80, 95% CI 0.59 to 1.09, p = 0.15). Also, HF without preceding MI (n = 187) was decreased (HR 0.73, 95% CI 0.54 to 0.97, p = 0.03). In conclusion, atorvastatin 80 mg was more efficient than simvastatin 20 to 40 mg in preventing development of HF in patients with previous MI.

  • 286.
    Strålfors, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    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.
    Insulinets verkningsmekanism och insulinresistens vid typ 2 diabetes2005In: Incitament, ISSN 1103-503X, no 7, p. 536-538Article in journal (Refereed)
  • 287.
    Szabó, Zoltan
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Andersson, Rolf
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Intraoperative muscle and fat metabolism in diabetic patients during coronary artery bypass grafting surgery: a parallel microdialysis and organ balance study2009In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 103, no 2, p. 166-172Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Surgical trauma causes stress and inflammatory reactions with elevated serum free fatty acids (FFA) and glucose levels characteristic of intraoperative insulin resistance. Our aim was to compare microdialysis findings with those using the classical organ balance technique and to test the clinical feasibility of microdialysis during cardiac surgery. METHODS: Nine diabetic and nine non-diabetic patients, undergoing routine coronary artery bypass grafting surgery, were studied using both microdialysis and the organ balance technique in the brachio-radial muscle of the forearm, and microdialysis in the pre-pectoral fat tissue. Glucose, lactate, and glycerol were measured in arterial and venous plasma and in the microdialysate before administration of heparin, at the release of the aortic cross-clamp, and before transfer to the intensive care unit. RESULTS: Glucose release from the diabetic muscle at the last sampling time was detected. This was confirmed by a negative glucose A-I (arterial-interstitial difference) in the muscle. No differences were observed regarding lipolysis in the fat tissue in terms of A-I of glycerol. Intergroup differences were detected at the first sampling time, where arterial plasma glucose and plasma insulin levels were higher and muscle interstitial glucose lower in the diabetic patients. Plasma insulin was higher in the diabetic patients even at the final measurement time. CONCLUSIONS: In terms of lipolysis in the fat tissue and glucose transport in the muscle, the non-diabetic patients were metabolically 'diabetics' during surgery. Despite strict blood glucose control, disturbances in glucose homeostasis in the diabetic muscle persist. Microdialysis was easy to use during cardiac surgery.

  • 288.
    Szabó, Zoltán
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Andersson, Rolf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Insulin resistance during coronary surgery in diabetic and non-diabetic patients-parallel microdialysis and organ balance technique studying skeletal muscle (preliminary results)2007In: Diabetologia(ISSN 0012-186X), vol 50, 2007, Vol. 50, p. 275-276Conference paper (Refereed)
  • 289.
    Szabó, Zoltán
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Andersson, Rolf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Insulin resistance during coronary surgery in diabetic and non-diabetic patients-parallel microdialysis and organ balance technique studying skeletal muscle (preliminary results)2007In: European Association for the Study of Diabetes EASD,2007, 2007Conference paper (Refereed)
    Abstract [en]

        

  • 290.
    Szabó, Zoltán
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Intraoperative insulin resistance during coronary surgery in diabetic and non-diabetic patients- preliminary results2007In: EASD: Diabetes Cardiovascular Disease Study Group Meeting,2007, 2007Conference paper (Other academic)
  • 291.
    Szabó, Zoltán
    et al.
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    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.
    Håkanson, Erik
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Jorfeldt, Lennart
    Department of Thoracic Physiology, Karolinska Hospital, Stockholm, Sweden.
    Svedjeholm, Rolf
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Effects of high-dose glucose–insulin–potassium on myocardial metabolism after coronary surgery in patients with Type II diabetes2001In: Clinical Science, ISSN 0143-5221, Vol. 101, no 1, p. 37-43Article in journal (Refereed)
    Abstract [en]

    The effects of glucose–insulin–potassium (GIK) on cardiac metabolism have been studied previously in non-diabetic patients after cardiac surgery. Although patients with diabetes mellitus can be expected to benefit most from such treatment, the impact of GIK in diabetic patients undergoing cardiac surgery remains unexplored. Therefore the present study investigates the effects of high-dose GIK on myocardial substrate utilization after coronary surgery in patients with Type II diabetes. A total of 20 patients with Type II diabetes undergoing elective coronary surgery were randomly allocated to either post-operative high-dose GIK or standard post-operative care, including insulin infusion if necessary to keep blood glucose below 10 mmol/l. Myocardial substrate utilization was studied using the coronary sinus catheter technique. Haemodynamic state was assessed with the aid of Swan–Ganz catheters. High-dose GIK caused a shift towards carbohydrate utilization, with significant lactate uptake throughout the study period and significant uptake of glucose after 4 h. Arterial levels of non-esterified fatty acids and b-hydroxybutyric acid decreased, and after 1 h no significant uptake of these substrates was found. Increases in the cardiac index and stroke volume index were found in patients treated with high-dose GIK. A decrease in systemic vascular resistance was found both in the control group and in the high-dose GIK group. We conclude that high-dose GIK can be used in diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of non-esterified fatty acids and b-hydroxybutyric acid. This could have implications for treatment of the diabetic heart in association with surgery and ischaemia.

  • 292. Söderlund, Gustav
    et al.
    Haarhaus, Mathias
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Chisalita, Ioana Simona
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Inhibition of puromycin-induced apoptosis in breast cancer cells by IGF-I occurs simultaneously with increased protein synthesis2004In: Neoplasma (Bratislava), ISSN 0028-2685, E-ISSN 1338-4317, Vol. 51, no 1Article in journal (Refereed)
    Abstract [en]

    The objective of the following work was to study the apoptosis inducing effect of puromycin in MCF-7 breast cancer cells and compare this effect with cycloheximide and emetine, 2 other inhibitors of protein synthesis. We also wished to investigate if the apoptosis modulating effect of insulin-like growth factor-1 (IGF-I) was similar for the 3 inhibitors. An immunological assay, quantifying mono- and oligonucleosome fragments and morphological criteria after nuclear staining, were used to study apoptosis. Protein synthesis was measured by incorporation of 3H-leucine in the cells, and solution hybridization and Western blot were performed to estimate IGF-I receptor m-RNA and IGF-I receptor protein respectively. Puromycin at 0.5 μg/ml induced a high level of apoptosis in MCF-7 breast cancer cells, although there was still a non-negligible amount of synthesized protein. In the case of cycloheximide and emetine, apoptosis occured when protein synthesis was almost completely blocked. IGF-I at a concentration of 10 ng/ml significantly reduced the level of apoptosis induced by puromycin, emetine, or cycloheximide. We also noticed a parallel increase in 3H-leucine incorporation when apoptosis induced by puromycin was lowered as an effect of IGF-I, in contrast to cycloheximide and emetine where IGF-I reduced the apoptosis level without increasing the 3H-leucine incorporation. At a higher concentration of puromycin (5. 7 μg/ml), which blocked protein synthesis, IGF-I at 10 ng/ml did not reduce apoptosis. The level of IGF-I receptor m-RNA was not influenced by the use of a concentration of puromycin (0.5 μg/ml) inducing a high degree of apoptosis. These results suggest, that reduction of puromycin-induced apoptosis by IGF-I occurs simultaneously with increased protein synthesis, in contrast to emetine and cycloheximide. Furthermore it would appear that puromycin-induced apoptosis is not caused by reduced levels of IGF-I receptors.

  • 293. Teml, Alexander
    et al.
    Schwab, Matthias
    Hommes, Daan W
    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.
    Lukas, Milan
    Feichtenschlager, Thomas
    Florin, Timothy
    Seiderer, Julia
    Petritsch, Wolfgang
    Bokemeyer, Bernd
    Kreisel, Wolfgang
    Herrlinger, Klaus R
    Knoflach, Peter
    Bonaz, Bruno
    Klugmann, Thomas
    Herfarth, Hans
    Pedarnig, Nikolaus
    Reinisch, Walter
    A systematic survey evaluating 6-thioguanine-related hepatotoxicity in patients with inflammatory bowel disease2007In: Wiener Klinische Wochenschrift, ISSN 0043-5325, E-ISSN 1613-7671, Vol. 119, no 17-18, p. 519-526Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Drug-induced liver injury was recently reported as a major complication leading to hepatic nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease (IBD) and 6-thioguanine (6-TG) therapy. The aim of the study was to evaluate the prevalence of 6-TG-related hepatotoxicity in a large multi-centered IBD population by means of a systematic online survey. METHODS: Clinical and laboratory data, imaging techniques (sonography, CT, MRI) and histology of liver biopsies were surveyed in IBD patients treated with 6-TG. The decision on whether liver imaging and/or liver biopsy were performed was exclusively at the discretion of the investigator. RESULTS: 6-TG use was fully documented in 296 patients (median treatment duration 56 weeks, range < 1-207). Laboratory signs of drug-induced liver injury were found in 43 patients (14.5%). Liver imaging revealed pathologic results in 68/176 patients (38.6%). Liver biopsy was performed in a subset of 60 patients, using silver-reticulin staining (n = 59), NRH was considered in 16 patients (27.1%). Age was the only independent, albeit weak, risk factor for development of NRH. CONCLUSION: This large online survey confirms the strong association between 6-TG treatment and the significant risk of development of NRH in patients with IBD. The definitive diagnosis of NRH depends solely upon liver biopsy. © 2007 Springer-Verlag.

  • 294.
    Tengblad, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Engvall, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Lindström, Torbjörn
    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.
    Mölstad, Sigvard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice.
    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.
    Östgren, Carl-Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland.
    Sagittal abdominal diameter is strongly associated with Arterial stiffness and Left ventricular mass in patients with type 2 diabetes.2007In: EASD2,2007, 2007Conference paper (Other academic)
  • 295.
    Tham, E.
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden, Department of Molecular Medicine and Surgery, Center of Molecular Medicine L8:02, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden.
    Grandell, U.
    Department of Clinical Genetics, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden.
    Lindgren, E.
    Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
    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.
    Skogseid, B.
    Department of Medical Sciences, Uppsala University, Uppsala University Hospital, 75185 Uppsala, Sweden.
    Nordenskjold, M.
    Nordenskjöld, M., Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden.
    Clinical testing for mutations in the MEN1 gene in Sweden: A report on 200 unrelated cases2007In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, no 9, p. 3389-3395Article in journal (Refereed)
    Abstract [en]

    Context: Multiple endocrine neoplasia type 1 (MEN1) is a tumor syndrome of the parathyroid, endocrine pancreas, and anterior pituitary caused by mutations in the MEN1 gene on 11q13. Objective: The goal of this study was to determine the MEN1 mutation spectrum and detection rate among Swedish patients and identify which patient categories should be tested for MEN1 mutations. Design/Setting/Patients: DNA sequences and referral forms from patients referred to the Department of Clinical Genetics at Karolinska University Hospital, Sweden, for clinical MEN1 mutation screening were analyzed. The mutation status of 371 patients (including 200 probands) was ascertained, and the multiplex ligation-dependent probe amplification (MLPA) assay was evaluated for the detection of large deletions. Main Outcome Measure: The main outcome measure was MEN1 genotypes. Results: Forty-eight of 200 index cases (24%) shared 40 different mutations (18 novel). A total of 69% of all mutations resulted in a truncated protein. Two large deletions were detected by MLPA. A total of 94% of all MEN1 families had a mutation in the coding region of the MEN1 gene. A total of 6% of sporadic cases had MEN1 mutations. There was no correlation between severe disease and mutation type or location. Conclusions: A total of 4% of all mutations were large deletions, and MLPA is now included in our standard MEN1 mutation screening. Individuals with at least one typical endocrine tumour and at least one of the following: 1) a first-degree relative with a major endocrine tumor, 2) an age of onset less than 30 yr, and/or 3) multiple pancreatic tumors/parathyroid hyperplasia were most likely to harbor a mutation, thus these patients should be screened for MEN1 mutations. Copyright © 2007 by The Endocrine Society.

  • 296.
    Theibaut, R
    et al.
    AP HP, INSERM.
    Douchin, V
    AP HP, INSERM.
    Jung, C
    AP HP, INSERM.
    Merlin, F
    AP HP, INSERM.
    Colombel, J F
    Hop Calmette.
    Lemann, M
    Hop St Louis.
    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.
    Tysk, C
    Orebro University Hospital.
    OMorain, C
    Trinity College Dublin.
    Gassull, M
    Hospital Badalona Germans Trias and Pujol.
    Finkel, Y
    Karolinska Institute.
    Zouali, H
    Fdn Jean Dausset.
    Pascoe, L
    Fdn Jean Dausset.
    Hugot, J P
    AP HP, INSERM.
    Letter: RIP2 Polymorphisms in Inflammatory Bowel Diseases2011In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 17, no 4, p. 1055-1055Article in journal (Other academic)
    Abstract [en]

    n/a

  • 297.
    Thiebaut, R
    et al.
    University of Paris.
    Kotti, S
    University of Paris.
    Jung, C
    University of Paris.
    Merlin, F
    University of Paris.
    Colombel, J F
    Hop Calmette.
    Lemann, M
    Hop St Louis.
    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.
    Tysk, C
    University of Örebro.
    Morain, M O
    Adelaide & Meath Hospital.
    Gassull, M
    Hospital University Germans Trias & Pujol.
    Binder, V
    Herlev Hospital.
    Finkel, Y
    Karolinska Children's Hospital.
    Pascoe, L
    CEPH, Paris.
    Hugot, J-P
    Hop Robert Debre.
    TNFSF15 Polymorphisms Are Associated With Susceptibility to Inflammatory Bowel Disease in a New European Cohort2009In: AMERICAN JOURNAL OF GASTROENTEROLOGY, ISSN 0002-9270, Vol. 104, no 2, p. 384-391Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Inflammatory bowel disease (IBD), e. g., Crohns disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD.

    METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied.

    RESULTS: The previously reported "high-risk" haplotype (A) was associated with IBD (P = 0.001) (OR = 1.25 (1.05-1.50)) and CD (P = 0.02) (OR = 1.31 (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A.

    CONCLUSIONS: This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.

  • 298.
    Thorn, Hans
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Stenkula, Karin G.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Karlsson, Margareta
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Örtegren Kugelberg, Unn
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    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.
    Gustavsson, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Cell surface orifices of caveolae and localization of caveolin to the necks of caveolae in adipocytes2003In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 14, no 10, p. 3967-3976Article in journal (Refereed)
    Abstract [en]

    Caveolae are noncoated invaginations of the plasma membrane that form in the presence of the protein caveolin. Caveolae are found in most cells, but are especially abundant in adipocytes. By high-resolution electron microscopy of plasma membrane sheets the detailed structure of individual caveolae of primary rat adipocytes was examined. Caveolin-1 and -2 binding was restricted to the membrane proximal region, such as the ducts or necks attaching the caveolar bulb to the membrane. This was confirmed by transfection with myc-tagged caveolin-1 and -2. Essentially the same results were obtained with human fibroblasts. Hence caveolin does not form the caveolar bulb in these cells, but rather the neck and may thus act to retain the caveolar constituents, indicating how caveolin participates in the formation of caveolae. Caveolae, randomly distributed over the plasma membrane, were very heterogeneous, varying in size between 25 and 150 nm. There was about one million caveolae in an adipocyte, which increased the surface area of the plasma membrane by 50%. Half of the caveolae, those larger than 50 nm, had access to the outside of the cell via ducts and 20-nm orifices at the cell surface. The rest of the caveolae, those smaller than 50 nm, were not open to the cell exterior. Cholesterol depletion destroyed both caveolae and the cell surface orifices.

  • 299.
    Tikkanen, Matti J
    et al.
    Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, FIN-00290 Helsinki, Finland.
    Szarek, Michael
    Pfizer Inc, New York, NY USA.
    Fayyad, Rana
    Pfizer Inc, New York, NY USA.
    Holme, Ingar
    Ullevaal Univ Hosp, Ctr Prevent Med, Oslo, Norway.
    Cater, Nilo B
    Pfizer Inc, New York, NY USA.
    Faergeman, Ole
    Aarhus Univ Hosp, Dept Med Cardiol A, DK-8000 Aarhus, Denmark.
    Kastelein, John J P
    Acad Hosp Amsterdam, Dept Vasc Med, Amsterdam, Netherlands.
    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.
    Lytken Larsen, Mogens
    Department of Medicine-Cardiology A, Århus University Hospital, Århus, Denmark.
    Lindahl, Christina
    Pfizer Sweden, Sollentuna, Sweden.
    Pedersen, Terje R
    Ullevaal Univ Hosp, Ctr Prevent Med, Oslo, Norway.
    Total Cardiovascular Disease Burden: Comparing Intensive With Moderate Statin Therapy Insights From the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) Trial2009In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 54, no 25, p. 2353-2357Article in journal (Refereed)
    Abstract [en]

    Objectives This post-hoc analysis of the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial was designed to assess the comparative treatment efficacy of high-dose atorvastatin and usual-dose simvastatin for the prevention of events subsequent to the first event, using the Wei, Lin, and Weissfeld method. Background Time-to-first-event analysis of data is frequently utilized to provide efficacy outcome information in coronary heart disease prevention trials. However, during the course of such long-term trials, a large number of events occur subsequent to the first event, the analysis of which will be precluded by this approach. Methods The Wei, Lin, and Weissfeld method allows the analysis of repeated occurrence of events of the same type or of entirely different natures. It regards the recurrence times as multivariate event (failure) times, and models the marginal (individual) distribution for each event with the Cox proportional hazards model. Results In the IDEAL trial, compared with patients taking simvastatin 20 to 40 mg daily, patients receiving atorvastatin 80 mg daily had their relative risk of a first cardiovascular event reduced by 17% (p less than 0.0001), of a second by 24% (p less than 0.0001), of a third by 19% (p = 0.035), of a fourth by 24% (p = 0.058), and of a fifth by 28% (p = 0.117). Conclusions Our results indicate that intensive statin therapy continues to be more effective than standard statin therapy, even beyond the first event, and suggest that clinicians should not hesitate to prescribe high-dose statin therapy for patients experiencing multiple recurrent cardiovascular events.

  • 300.
    Tikkanen, M.J.
    et al.
    Helsinki University Central Hospital.
    Holme, I.
    Ullevål University Hospital.
    Cater, N.B.
    Pfizer Inc.
    Szarek, M.
    Pfizer Inc.
    Faergeman, O.
    Århus University Hospital.
    Kastelein, J.J.P.
    Academic Hospital Amsterdam.
    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.
    Larsen, M.L.
    Århus University Hospital.
    Lindahl, C.
    Pfizer Sweden.
    Pedersen, T.R.
    Ullevål University Hospital.
    Comparison of Efficacy and Safety of Atorvastatin (80 mg) to Simvastatin (20 to 40 mg) in Patients Aged less than65 Versus =65 Years With Coronary Heart Disease (from the Incremental DEcrease through Aggressive Lipid Lowering [IDEAL] Study)2009In: American Journal of Cardiology, ISSN 0002-9149, Vol. 103, no 5, p. 577-582Article in journal (Refereed)
    Abstract [en]

    The efficacy and safety of atorvastatin (80 mg/day) versus simvastatin (20 to 40 mg/day) in older (age =65 years) versus younger (less than65 years) patients were assessed in a prespecified secondary analysis of the 8,888 patients with myocardial infarction in the IDEAL trial, a randomized open-label study. Several cardiovascular end points were evaluated, including the occurrence of a first major coronary event (MCE; nonfatal myocardial infarction, coronary heart disease death, or resuscitated cardiac arrest), the primary end point of the trial, and occurrence of any cardiovascular event (MCE, stroke, revascularization, unstable angina, congestive heart failure, and peripheral artery disease). Although there were no significant interactions between age and treatment, the magnitude of effect in favor of atorvastatin was higher in younger versus older patients (occurrence of first MCE, hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.66 to 0.98; and HR 0.95, 95% CI 0.80 to 1.15, respectively; occurrence of any cardiovascular (CV) event, HR 0.80, 95% CI 0.71 to 0.89; and HR 0.88, 95% CI 0.79 to 0.99, respectively). These results were likely influenced by adherence, which was lower in older patients and those receiving atorvastatin compared with those receiving simvastatin. Rates of any reported serious adverse event were higher in older patients, but did not differ between the 2 statin groups. In conclusion, except for any CV events in the older group, significant reductions in primary and secondary end points were observed only in patients less than65 years of age. The safety of atorvastatin (80 mg) and simvastatin (20 to 40 mg) was similar in patients aged less than65 and greater than65 years with stable coronary disease.

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