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  • 51.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Ek, Anna-Christina
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Eriksson, Mats
    Huddinge University Hospital, Stockholm, Sweden.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Quality of life in familial hypercholesterolaemia families2001Konferansepaper (Annet vitenskapelig)
  • 52.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Ek, Anna-Christina
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Eriksson, Mats
    Huddinge University Hospital, Stockholm, Sweden.
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Quality of life in genetic disease: The example of familial hypercholesterolaemia2000Inngår i: Atherosclerosis XII, 2000Konferansepaper (Annet vitenskapelig)
  • 53.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin.
    Ek, Anna-Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Only one of four patients with familial hypercholesterolaemia reach cholesterol treatment goals in primary prevention2004Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 256, nr 2, s. 176-177Artikkel i tidsskrift (Annet vitenskapelig)
  • 54.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Ek, Anna-Christina
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Berterö, Carina
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    The meaning of quality of life among patients with familial hypercholesterolemia2004Inngår i: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 19, nr 4, s. 243-250Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Living with a genetic predisposition to disease may influence quality of life. The presence of premature disease can lead to an increased focus on family history and genetic predisposition.

    Objective: The purpose of this study was to describe quality of life in patients with the genetic disease, familial hypercholesterolemia, who are at an increased risk of premature coronary heart disease.

    Methods: Interviews from 12 adult patients with FH were analyzed using constant comparative analysis. The findings of this qualitative study revealed that for patients, quality of life was equated with harmony in life, the core category. Attaining harmony in life presumes satisfaction and togetherness. Cognizance of the threat of coronary heart disease and impending mortality is balanced by the support of togetherness and satisfaction that builds harmony in life.

    Conclusion: When caring for patients with familial hypercholesterolemia, it is important to meet each patient on his or her own level, and to support balance and their choices for maintaining or regaining harmony in life.

  • 55.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Ek, Anna-Christina
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Achievement of treatment goals2004Konferansepaper (Annet vitenskapelig)
  • 56.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Ek, Anna-Christina
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Achievement of treatment goals, adherence and disease knowledge in patients with familial hypercholesterolaemiaManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background: Effective treatment is available for patients with familial hypercholesterolaemia (FH). Nevertheless the treatment goal seems hard to reach in all patients. We investigated to what extent recommended international treatment goals were achieved for total cholesterol and low-density lipoprotein (LDL) cholesterol, adherence to drug treatment and if achievement of treatment goals was influenced by knowledge.

    Design: Cross-sectional design.

    Methods: Patients with FH, above 18 years of age, n=74, were asked to participate. Drug treatment, laboratory results, blood pressure and smoking were documented, a questionnaire on adherence and knowledge about FH was sent to the patients. Response rate for the questionnaire was 92 % (n=68).

    Results: The treatment goals for LDL cholesterol (< 3.0 mmol/L) and total cholesterol (<5.0 mmol/L) were reached in 23% and 22% of the patients, respectively. Patients with LDL cholesterol < 3.0 mmol/L who were on treatment followed the prescription to a significantly higher degree than patients with LDL cholesterol ≥ 3.0 mmol/L, (p=0.001). For patient knowledge, the mean was 6.8±2.2 out of 11 possible. The patients had knowledge about cholesterol, self-care prevention and the reason for drug treatment. Patients were less informed about the chance of getting FH and family history.

    Conclusion: Intensified drug treatment is motivated since 23 % of the patients with FH reached treatment goals. In spite of the absence of relation between LDL cholesterol level and knowledge in the present study, we believe that increased disease lmowledge would facilitate for patients to face the difficulties of the condition.

  • 57.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Ek, Anna-Christina
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Quality of life in family members in families with familial hypercholesterolemia2002Konferansepaper (Annet vitenskapelig)
  • 58.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Gullberg, Mats
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Ek, Anna-Christina
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Eriksson, Mats
    Centre for Metabolism Endocrinology, Huddinge University Hospital, Stockholm, Sweden.
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Quality of life in patients with familial hypercholesterolaemia2002Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 251, nr 4, s. 331-337Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives.  The primary aim of this study was to analyse quality of life in adult patients with familial hypercholesterolaemia (FH), a genetic disorder with increased risk of coronary heart disease (CHD). Secondary aims were to find explanatory factors for quality of life and anxiety.

    Design. A descriptive cross-sectional design was used.

    Setting.  Outpatients from lipid clinics at two university hospitals in Sweden were included. Patients with heterozygous FH and a randomly selected control group participated by filling out questionnaires.

    Subjects.  Two hundred and eighty patients with heterozygous FH above 18 years of age were asked, and 212 of whom 185 were free of overt CHD, participated. Of a control group of 2980 persons 1485 were included for comparison.

    Methods. We used Likert-type questionnaires: the Quality of Life Index (QLI) consisting of four subscales, the Hospital Anxiety and Depression Scale (HAD), the Mastery Scale measuring coping and a questionnaire on health and lipids constructed for FH patients.

    Results.  Patients with FH were significantly more satisfied with overall quality of life 21.8 ± 0.3 (SEM) vs. controls 21.1 ± 0.1 and this was also the case in three of four subscales, all differences P < 0.05. Anxiety about getting CHD was expressed amongst 86% of the patients with FH.

    Conclusions. Quality of life amongst patients with FH was at least as good as in controls but they were worried about getting CHD.

  • 59.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Ek, Anna-Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Akutkliniken.
    Disease knowledge and adherence to treatment in patients with familial hypercholesterolemia2006Inngår i: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 21, nr 2, s. 103-108Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 60.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Ek, Anna-Christina
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Familial hypercholesterolaemia and quality of life in family members2003Inngår i: Preventive Medicine, ISSN 0091-7435, E-ISSN 1096-0260, Vol. 36, nr 5, s. 569-574Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Awareness of genetic disease in the family may influence quality of life. The purpose of this study was to describe quality of life among nonaffected members of families with familial hypercholesterolaemia. All were aware of the risk for coronary heart disease. Their quality of life was compared with a reference group and with the patients with familial hypercholesterolesterolaemia themselves.

    Methods

    Names of family members (n = 129) were given by the patients with familial hypercholesterolaemia. A randomly selected reference group (n = 1485) and patients with familial hypercholesterolaemia (n = 185) were included for comparison. They all completed the questionnaire Quality of Life Index, the Hospital Anxiety and Depression Scale, and the Mastery Scale measuring coping. Family members and patients with familial hypercholesterolaemia also completed a questionnaire on health and lipids.

    Results

    Family members were more satisfied with family life, mean 22.1 ± 3.5 (SD), and psychological/spiritual life, 22.9 ± 4.0, than the reference group, 21.4 ± 4.3 and 21.1 ± 4.8, respectively; this was particularly expressed among partners, P < 0.05. Of family members, 91% were anxious about the patient with familial hypercholesterolaemia developing coronary heart disease.

    Conclusions

    Family members have as good a quality of life as members of the reference group, but they were anxious about the patient with familial hypercholesterolaemia developing coronary heart disease.

  • 61.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin.
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-endokrin.
    Ek, Anna-Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Akutkliniken.
    Quality of life in non affected family members of familial hypercholesterolemia families2002Inngår i: Konferens Familjefokuserad omvårdnad, Kalmar,2002, 2002Konferansepaper (Fagfellevurdert)
  • 62.
    Hollman, Gunilla
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Ek, Anna-Christina
    Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    The meaning of quality of life among patients with familial hypercholesterolaemia2003Konferansepaper (Annet vitenskapelig)
  • 63.
    Holmer, Helene
    et al.
    Centralsjukhuset, Kristianstad, Sweden.
    Svensson, Johan
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Rylander, Lars
    Lund University, Sweden.
    Johansson, Gudmundur
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Rosén, Thord
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Bengtsson, Bengt Åke
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Thorén, Marja
    Karolinska University Hospital Solna, Stockholm, Sweden .
    Höybye, Charlotte
    Karolinska University Hospital Solna, Stockholm, Sweden.
    Degerblad, Marie
    Karolinska University Hospital Solna, Stockholm, Sweden.
    Bramnert, Margareta
    University Hospital, Malmö, Sweden.
    Hägg, Erik
    University Hospital, Umeå, Sweden.
    Edén Engström, Britt
    Uppsala University Hospital, Sweden.
    Ekman, Bertil
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Norrving, Bo
    Lund University Hospital, Sweden.
    Hagmar, Lars
    Lund University, Sweden.
    Erfurth, Eva-Marie
    Lund University Hospital, Sweden.
    Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone2007Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, nr 9, s. 3560-3567Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus (T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity. Copyright © 2007 by The Endocrine Society.

  • 64.
    Holmer, Helene
    et al.
    Centralsjukhuset, Kristianstad, Sweden.
    Svensson, Johan
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Rylander, Lars
    Lund University, Sweden.
    Johansson, Gudmundur
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Rosén, Thord
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Bengtsson, Bengt-Åke
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Thorén, Marja
    Karolinska University Hospital Solna, Stockholm, Sweden .
    Höybye, Charlotte
    Karolinska University Hospital Solna, Stockholm, Sweden .
    Degerblad, Marie
    Karolinska University Hospital Solna, Stockholm, Sweden .
    Bramnert, Margareta
    University Hospital, Malmö, Sweden.
    Hägg, Erik
    University Hospital, Umeå, Sweden.
    Engström, Britt Edén
    Uppsala University Hospital, Sweden.
    Ekman, Bertil
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Thorngren, Karl-Göran
    University Hospital, Lund, Sweden.
    Hagmar, Lars
    Lund University, Sweden.
    Erfurth, Eva-Marie
    Lund University Hospital, Sweden.
    Fracture incidence in GH-deficient patients on complete hormone replacement including GH2007Inngår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 22, nr 12, s. 1842-1850Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients wilh confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29, 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR. 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54, 95% CI 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.

  • 65.
    Jacobsson, Leif S.
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Persson, Karin
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Aberg, Gunnar
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Andersson, Rolf G. G.
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Karlberg, Bengt E.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Endokrin- och magtarmmedicinska kliniken.
    Antiatherosclerotic Effects of the Angiotensin-Converting Enzyme Inhibitors Captopril and Fosinopril in Hypercholesterolemic Minipigs1994Inngår i: Journal of Cardiovascular Pharmacology, ISSN 0160-2446, E-ISSN 1533-4023, Vol. 24, nr 4, s. 670-677Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We evaluated the two angiotensin-converting enzyme (ACE) inhibitors captopril and fosinopril with regard to possible antiatherosclerotic effects in minipigs. Experimental hypercholesterolemia and atherosclerosis was produced in 33 minipigs of the Gottingen strain by an egg yolk/cholesterol-enriched diet for 1 year. One group (n = 11) was fed the atherogenic diet alone and served as a control. A second group (n = 11) received captopril (80 mg/kg/day) added to the atherogenic diet, and a third group (n = 11) was treated in the same manner but with fosinopril (8 mg/kglday). The drug treatments produced significant reduction in serum ACE activity associated with a reactive increase in plasma renin activity (PRA), but had only minor effects on plasma lipids and lipoproteins. At the end of the treatment period, all animals were killed and examined for degree of atherosclerosis. The percentage of atherosclerotic area in the abdominal aorta was significantly lower in both drug-treated groups as compared with controls. Furthermore, accumulation of cholesterol in the thoracic and abdominal aorta was inhibited by drug treatment. Finally, the percentage of intimal thickening in abdominal aorta was significantly reduced in the drug-treated groups. In conclusion, the ACE inhibitors captopril and fosinopril inhibited development of atherosclerosis in hypercholesterolemic minipigs.

  • 66.
    Jacobsson, Leif
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Yuan, Xi Ming
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi.
    Ziedén, Bo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin.
    Olsson, Anders G
    IMV Faculty ofHealth Sciences, Linköping.
    Effects of α-tocopherol and astaxanthin on LDL oxidation and atherosclerosis in WHHL rabbits2004Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 173, nr 2, s. 231-237Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to evaluate the influence of α-tocopherol and astaxanthin on low-density lipoprotein (LDL) oxidation lag time and atherosclerotic lesion formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one, 3-month-old WHHL rabbits were divided into three experimental groups. One group (n=10) was fed standard rabbit feed alone and served as a control, a second group (n=11) was supplied with the same feed containing 500mg α-tocopherol/kg and a third group (n=10) was given a feed containing 100mg astaxanthin/kg. Plasma lipids, lipoproteins and LDL oxidation lag time were followed for 24 weeks. At the end of the treatment period, the animals were killed and the thoracic aorta was used for evaluation of the degree of atherosclerosis. Colour photographs of the intimal surface of the vessel were taken for determination of the atherosclerotic area. Cross-sections of the thoracic aorta were used for histological examination and for determination of intimal thickening. Specimens of the vessel were used for determination of the tissue cholesterol content. Plasma cholesterol remained at a high level during the time of the experiment and there were no differences between the experimental groups. After 24 weeks, the LDL oxidation lag time was 53.7±1.7min, 109±4min (P<0.001) and 56.4±3.4min (P=0.47) in the control, α-tocopherol and astaxanthin groups, respectively. In the thoracic aorta, the atherosclerotic area was 80.7±5.1%, 67.1±6.7% (P=0.13) and 75.2±5.7% (P=0.49) in the control, α-tocopherol and astaxanthin groups, respectively. The intimal thickening was 45.6±3.2%, 44.0±4.1% (P=0.89) and 40.0±4.5% (P=0.33) in the control, α-tocopherol and astaxanthin groups, respectively. Finally, the cholesterol content was 107±9μmol/g, 95.7±11. 5μmol/g (P=0.31) and 101±5μmol/g (P=0.33) in the control, α-tocopherol and astaxanthin groups, respectively. It can be concluded that α-tocopherol but not astaxanthin prolonged the LDL oxidation lag time. The two antioxidative substances did not prevent atherogenesis in WHHL rabbits in this setting.

  • 67.
    Janke, J
    et al.
    Franz Volhard Clinic.
    Schupp, M
    n/a.
    Engeli, S
    n/a.
    Gorzelniak, K
    n/a.
    Boschmann, M
    n/a.
    Sauma, Lilian
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Nystrom, Fredrik H
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Jordan, J
    n/a.
    Luft, FC
    n/a.
    Sharma, AM
    n/a.
    Angiotensin type 1 receptor antagonists induce human in-vitro adipogenesis through peroxisome prolifertor-activated receptor-gamma activation2006Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 24, nr 9, s. 1809-1816Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: In clonal animal cells, certain angiotensin receptor blockers (ARB) activate the peroxisome proliferator-activated receptor-gamma (PPARgamma). The aim of this work was to validate that observation in human cells and humans. METHODS: We investigated the induction of in-vitro adipogenesis and the activation of PPARgamma-target genes, adiponectin and lipoprotein lipase, by ARB in human preadipocytes. We also studied PPARgamma response-element-driven luciferase reporter gene activation in human adipocytes. Finally, we treated 14 obese men for 10 days with placebo crossed over with 150 mg/day irbesartan. Subcutaneous fat was analyzed for mRNA expression of adiponectin and lipoprotein lipase. RESULTS: Telmisartan and irbesartan, and to a lesser degree losartan, induced adipogenesis and activated PPARgamma-target genes. This stimulation of PPARgamma-target genes was prevented by the PPARgamma antagonist GW9662. Eprosartan had no effect. Paradoxically, all ARB activated the luciferase reporter gene. PPARgamma activity increased approximately two-fold with pioglitazone and 1.5-fold with the ARB in all assays. In the cross-over clinical study, irbesartan lowered blood pressure but had no effect on adiponectin or lipoprotein lipase mRNA expression. CONCLUSIONS: Our data are the first to show that ARB induce adipogenesis and PPARgamma-target gene expression in human adipocytes. Pharmacokinetic differences may contribute to the heterogeneous effects on metabolism and preadipocyte differentiation. In humans, larger doses of ARB, longer treatments, or both may be required to activate PPARgamma in adipose cells.

  • 68.
    Jansson, Kjell
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Dahlström, Ulf
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Karlberg, B E
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin.
    Karlsson, E
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Nylander, Eva
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    Nyqvist, O
    Karlberg, K-E
    The circulating renin-angiotensin system during treatment with mteprlol or captopril in patients with heart failure due to non-ischaemic dilated cardiomyopathy.1999Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 245, s. 435-443Artikkel i tidsskrift (Fagfellevurdert)
  • 69.
    Jendle, Johan H.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Intrapulmonary insulin: Experimental and clinical studies1996Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    After intrapulmonary insulin administration was first reported in 1925, the development of highly efficient nebulisers has once again made this area interesting. Therefore, the distribution and retention of aerosol produced by a new jet nebuliser was evaluated in an animal model. Anaesthetized and mechanically ventilated pigs were given radiolabelled aerosol, insulin or the combination of insulin and a surface active agent. After sacrifice the lungs were histologically examined or scintigrafted using a gamma camera. The distribution of aerosol was even and reached the peripheral parts of the lung parenchyma. The retention of insulin was estimated to be 36%. No morfological changes were observed.

    The biological effects of intrapulmonary insulin administration were evaluated in 14 pigs in a double-blind placebo controlled randomized intervention trial. Insulin at a dose of 10 and 40 U as well as 0.9% saline solution was given as aerosol. The blood glucose and serum insulin concentrations were assessed at certain intervals during 90 min. The mean blood glucose concentration fell from 4.6 ± 0.1 to 2.8 ± 0.2 mmol/L reaching a nadir 40 min after the start of nebulisation. Serum insulin rose from 5.2 ± 0.1 to 25 ± 9 mUlL.

    Eight healthy volunteers received insulin aerosol in three different doses (40, 80 and 160 U) in a double-blind randomized intervention study. As a control saline solution was given. Blood glucose, serum insulin and serum C-peptide were assessed during 120 min. A reduction of the mean bloodglucose concentration was seen, falling from 4.3 ± 0.2 to 2.8 ± 0.2 mmol/L after 160 U. Serum insulin rose from 9.5 ± 1.5 mUlL to 26.1 ± 2.5 mUlL. Serum C-peptide was suppressed in a dosedependent fashion.

    Twelve patients with NIDDM treated with anti-diabetic drugs were given intrapulmonary insulin in a double-blind randomized intervention trial. Insulin was given at a dose of 2.5 U/kg BW. As a control saline solution was given. Blood glucose, serum insulin and serum C-peptide were assessed during 180 min. Blood glucose fell from 10.2 ± 0.5 to 6.1 ± 0.5 mmol/L. Serum insulin rose from 11.2 ± 1.8 to 28.0 ± 2.6 mUlL. Likewise serum C-peptide was suppressed after inhaling the insulin aerosol.

    A flow cytometric assay was developed to assess the changes of the F-actin content and DNA synthesis in adherent cells after short-time and long-term stimulation with insulin and PDGF. No stimulatory effect on the DNA synthesis was seen on lung fibroblasts after repetitive insulin treatment.

    Thus, intrapulmonary insulin administration has been evaluated in experimental and clinical studies. Significant lowering of the blood glucose concentrations and clinically relevant serum insulin concentrations were achieved. No subjective adverse effects were reported. No changes in lung function could be observed experimentally.

  • 70.
    Jennersjö, Cecilia
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Akutkliniken.
    Fagerberg, Inger
    Karlander, Sven
    Lindahl, Tomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Normal D-dimer concentration is a common finding in symptomatic outpatients with distal deep vein thrombosis2005Inngår i: Blood Coagulation and Fibrinolysis, ISSN 0957-5235, E-ISSN 1473-5733, Vol. 16, nr 7, s. 517-523Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The D-dimer analysis has been shown to have a high sensitivity and a high negative predictive value for the exclusion of deep vein thrombosis (DVT). However, most D-dimer studies, including recent clinical management studies, are performed without examination of the calf veins and/or performed on patient populations with a predominance of proximal DVT. The purpose of this study was to evaluate the diagnostic performance of the D-dimer test in a population with a suspected high incidence of distal DVT. In the present study, 393 outpatients with clinically suspected symptomatic DVT of the lower extremities were examined with whole-leg duplex ultrasonography. The D-dimer analysis was performed using an automated micro-latex assay (Tina-quant). A total of 137 of 393 patients had a proven DVT, with the majority presenting with distal DVT (59%). Twenty-eight out of 81 patients with distal DVT had a normal D-dimer, compared with two of 56 patients with proximal DVT. The sensitivity for distal DVT was only 65% compared with 96% for proximal DVT, the negative predictive values were 84 and 99%, respectively. In conclusion, the prevalence of distal DVT in a study population seems to have a great impact on the diagnostic performance of the D-dimer analysis. The study results also show that normal D-dimer levels do not exclude distal DVT in outpatients, instead, it can be hypothesized that normal D-dimer levels exclude DVT that require treatment, as indicated by the good outcome in recent management studies. © 2005 Lippincott Williams & Wilkins.

  • 71.
    Jerotskaja, Jana
    et al.
    Department of Biomedical Engineering, Technomedicum, Tallinn University of Technology, Tallinn, Estonia.
    Uhlin, Fredrik
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Lauri, Kai
    Department of Biomedical Engineering, Technomedicum, Tallinn University of Technology, Tallinn, Estonia.
    Tanner, Risto
    Department of Biomedical Engineering, Technomedicum, Tallinn University of Technology, Tallinn, Estonia.
    Luman, Merike
    Department of Dialysis and Nephrology, North-Estonian Regional Hospital, Tallinn, Estonia.
    Fridolin, Ivo
    Department of Biomedical Engineering, Technomedicum, Tallinn University of Technology, Tallinn, Estonia.
    A multicentre study of an enhanced optical method for measuring concentration of uric acid removed during dialysis.2009Inngår i: Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2009. EMBC 2009, 2009, nr 1, s. 1477-1480Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to compare concentration measurements of uric acid (UA) removed during dialysis by two algorithms based on UV-absorbance and the 1st derivate of UV absorbance. Ten uremic patients from Tallinn and ten from Linköping, during 30+40 haemodialysis treatments, were followed at the Departments of Dialysis and Nephrology at North-Estonian Medical Centre and at Linköping University Hospital. The dialysate samples were taken and analyzed by means of UA concentration at the chemical laboratory and with a double-beam spectrophotometer. UV absorbance and derivate of UV absorbance was transformed into UA concentration in the spent dialysate using the regression models from the calibration set of material, noted as UV-absorbance (UV_A) and the 1st derivate of UV absorbance (UV_D) method. These models were tested on validation set of material and concentrations of UA from the two methods were compared regarding mean values and SD. Mean concentration of UA were 52.7 +/- 25.0 micromol/l measured at the chemical laboratory (UA_Lab), 54.9 +/- 23.8 micromol/l determined by UV_A and 52.9 +/- 23.0 micromol/l determined by UV_D. The results of mean concentrations were not significantly different (p >/= 0.54). The systematic errors were -7.8 % and -3.3% and random errors were 15.8 % and 10.4 % using UV_A and UV_D respectively. The systematic and random errors were significantly different (p < 0.05) indicating that the new algorithm enables more accurate UA estimation.

  • 72. Jonasson, L
    et al.
    Linderfalk, C
    Olsson, J
    Wikby, A
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Systemic T-cell activation in stable angina pectoris2002Inngår i: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 89, nr 6, s. 754-756Artikkel i tidsskrift (Fagfellevurdert)
  • 73.
    Jones, A. Wayne
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, K. Å.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Kechagias, Stergios
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Effect of high-fat, high-protein, and high-carbohydrate meals on the pharmacokinetics of a small dose of ethanol1997Inngår i: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 44, nr 6, s. 521-526Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims To investigate whether the relative amounts of fat, carbohydrate (CHO), or protein in a meal influence the pharmacokinetics of a small dose of ethanol.

    Methods Nine healthy men received ethanol (0.30 g kg−1 body weight) on five occasions in a randomized cross-over fashion. On three occasions the dose of ethanol was consumed within 15 min of eating a standardized breakfast of similar volume and calorific value but containing different amounts of fat, CHO, and protein. On two other occasions the same dose of ethanol was ingested on an empty stomach (overnight fast) or administered by intravenous (i.v.) infusion over 30 min.

    Results The blood-ethanol profiles showed large inter and intraindividual variations, especially when ethanol was ingested after eating food. The peak blood-alcohol concentrations (BAC) were 16.6±4.0, 17.7±7.1, and 13.3±4.0 mg dl−1 (mean±s.d.) after fat, CHO, and protein-rich meals and 30.8±4.3 and 54.3±6.4 mg dl−1 after fasting and i.v. infusion, respectively. The corresponding areas under the concentration-time profiles (AUC) were 1767±549, 1619±760, 1270±406 mg dl−1 min after fat, CHO, and protein-rich meals compared with 3210±527 and 4786±446 mg dl−1  min after fasting and i.v. infusion, respectively. The time required to eliminate ethanol from the blood was shortened by 1–2 h in the fed-state.

    Conclusions Drinking ethanol after eating a meal, regardless of the nutritional composition, decreases the systemic availability of ethanol. Because gastric emptying is slow and more prolonged with food in the stomach, the delivery of ethanol to the duodenum and the liver will be highly variable as will the hepatic clearance of ethanol. Provided that portal venous BAC remains fairly low and ethanol metabolizing enzymes are not fully saturated then part of the dose of ethanol can be cleared by hepatic first-pass metabolism (FPM), as one consequence of Michaelis-Menten elimination kinetics.

  • 74. Kaminskas, A
    et al.
    Ziedén, Bo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Elving, B
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö. Östergötlands Läns Landsting, FHVC - Folkhälsovetenskapligt centrum, Förebygg.med.
    Kristenson, Margareta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö. Östergötlands Läns Landsting, FHVC - Folkhälsovetenskapligt centrum, Förebygg.med.
    Abaravicius, A
    Bergdahl, Björn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Kucinskiene, Z
    Adipose tissue fatty acids in men from two populations with different cardiovascular risk - the LiVicordia study.1999Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 59, s. 227-232Artikkel i tidsskrift (Fagfellevurdert)
  • 75. Kamwendo, K
    et al.
    Tingström, Pia
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin.
    Bergdahl, Björn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Svensson, E
    Effect of problem-based learning on stages of change for exercise behaviour in patients with coronary artery disease2004Inngår i: Physiotherapy Research International, ISSN 1358-2267, E-ISSN 1471-2865, Vol. 9, s. 24-32Artikkel i tidsskrift (Fagfellevurdert)
  • 76.
    Karlberg, B E
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Lins, L-E
    Hermansson, K
    Efficacy and safety of telmisartan, a selective AT. Receptor antagonist, compared with enalaprilin elderly patients with primary hypertensions.1999Inngår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 17, s. 293-302Artikkel i tidsskrift (Fagfellevurdert)
  • 77.
    Karlberg, Bengt
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Andrup, M
    Odén, A
    Trialists, T
    Efficacy and safety of a new long-acting drug combination, trandolapril/verapamil as compared to monotherapy in primary hypertension2000Inngår i: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 9, nr 2-3, s. 140-145Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To evaluate the clinical efficacy and safety of a new antihypertensive drug combination of trandolapril/verapamil compared to monotherapy with verapamil or trandolapril, in patients with mild to moderate primary hypertension. Design: A multicentre, prospective, randomized, double- blind, controlled cross-over study with specific statistical considerations. Settings: Eighteen primary health care centres and out-patient hospital clinics in Sweden. Patients: Two hundred and twenty-six outpatients with uncomplicated primary hypertension with a baseline sitting diastolic blood pressure (BP) between 95 and 115 mmHg. Interventions: After a 4-week placebo period, patients were randomized to treatment for 8 weeks with trandolapril/verapamil (2 mg/180 mg) or each drug alone (verapamil 240 mg, trandolapril 2 mg) for 8 weeks. Main outcome measures: Treatment responses (blood pressure (BP) fall and rate pressure product) to the three regimens with statistical comparison and also in relation to plasma concentrations of active renin (AR). Adverse events and safety were also evaluated. Results: The mean BP fall was significantly greater with the combination (20/15 mmHg), p < 0.00054, as compared to both trandolapril (14/11 mmHg) or verapamil (13/11) mmHg. The difference between verapamil and trandolapril was not significant. Rate pressure product decreased significantly more on the combination, p < 0.001, than on trandolapril or verapamil alone. Treatment response to trandolapril was positively correlated to initial AR (r = 0.30- 0.43). All treatments were well tolerated and safe. Conclusions: The new fixed drug combination trandolapril/verapamil was superior to monotherapy with either of these drugs alone regarding reduction of both BP and rate pressure product. This combination can be safely and effectively used for the treatment of mild to moderate primary hypertension.

  • 78. Karlsson, J
    et al.
    Lind, L
    Hallberg, P
    Michaelsson, K
    Kurland, L
    Kahan, T
    Malmqvist, K
    Ohman, KP
    Nyström, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Melhus, H
    Beta1-adrenergic receptor gene polymorphisms and response to beta1-adrenergic receptor blockade in patients with essential hypertension2004Inngår i: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 27, nr 6 SUPPL. 3, s. 347-350Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Studies suggest that the Ser49Gly and Arg389Gly polymorphisms in the β1-adrenergic receptor might be of functional importance for the cardiovascular system. Both have been associated with altered receptor activity in vitro, and with hypertension and cardiac failure in vivo. Hypothesis: The aim of this study was to test whether these polymorphisms were associated with the change in heart rate or blood pressure in patients with essential hypertension and left ventricular (LV) hypertrophy treated with the β1-adrenergic receptor blocker atenolol. Methods: Blood pressure and heart rate were measured in 101 hypertensive patients with echocardiographically verified LV hypertrophy, randomized in a double-blind study to treatment with either the β1-adrenergic receptor blocker atenolol or the angiotensin II type I receptor antagonist irbesartan. Changes in blood pressure and heart rate were evaluated after 12 weeks. Beta1-adrenergic receptor genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism. Results: We found no significant associations between the changes in the measured variables and either of the two polymorphisms. However, carriers of the 49Gly allele showed a tendency toward a greater reduction in heart rate compared with patients with the Ser/Ser49 genotype (p = 0.06). Conclusions: The Ser49Gly and Arg389Gly β1-adrenergic receptor polymorphisms do not seem to exert a major effect on the changes in heart rate and blood pressure during 12 weeks of treatment with atenolol in patients with essential hypertension and LV hypertrophy.

  • 79.
    Kechagias, Stergios
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Clinical Pharmacokinetics of Small Doses of Ethanol: Role of Gastric Emptying and Other Influences in the Upper Gastrointestinal Tract2001Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis deals with the clinical pharmacokinetics of small doses of ethanol as influenced by conditions in the proximal gut. The bioavailability of orally administered ethanol depends to a large extent on gastric emptying, which is influenced by pre-treatment with drugs and other clinically relevant factors in the upper gastrointestinal tract.

    The impact of the relative amount of carbohydrate, fat or protein in a test meal on the pharmacokinetics of a small dose of ethanol was studied in nine healthy male subjects. Drinking ethanol after eating a meal was compared with intake of the same dose consumed on an empty stomach or given intravenously. The peak blood alcohol concentration (BAC) and the area under the curve (AUC) were greatest when ethanol was given intravenously (100% availability). Drinking ethanol after a meal resulted in considerably lower peak BAC and AUC compared with drinking on an empty stomach. However, the macronutrient composition of the meal had no significant effect on the pharmacokinetics of ethanol as reflected in almost identical blood alcohol curves after high-fat, high-protein, or high-carbohydrate meals.

    The decreased bioavailability of ethanol after oral administration compared to intravenous infusion of the same dose can be explained by a first-pass metabolism (FPM). Some investigators attribute this FPM to the presence of alcohol dehydrogenase (ADH) in the gastric mucosa. Gastric ADH activity was studied in mucosal biopsies from 76 patients referred for upper gastrointestinal endoscopy. Those patients (n = 36) infected with H. pylori received treatment to eradicate the bacterium and repeat biopsies were obtained 2 months and one year later. There were no significant differences in gastric ADH activity between males and females and between different age groups. Gastric ADH activity was significantly decreased in the antrum among patients with H. pylori infection. After eradication of H. pylori, gastric ADH activity in the antrum was normalised within two months. No significant differences in the ADH activity were found in biopsies from the corpus. Histological examination of gastric biopsies showed that those exhibiting the most pronounced inflammation and histologic changes had significantly lower ADH activity compared with biopsies judged to have normal histology.

    Several drugs inhibit gastric ADH in vitro. Among them acetylsalicylic acid (ASA) was suggested to increase the bioavailability of orally administered ethanol. We studied the effect of low-dose ASA on the pharmacokinetics of a small dose of ethanol in 10 healthy men. Low-dose ASA (75 mg) decreased significantly the peak BAC and the time to reach peak BAC was also prolonged. The underlying mechanism appears to be delayed gastric emptying which was assessed by the paracetamol absorption test. To evaluate the effect of accelerating gastric emptying on ethanol pharmacokinetics, the prokinetic substance cisapride was given to the same 10 subjects. When ethanol was ingested 60 min after a meal pre-treatment with cisapride significantly increased peak BAC. However, this increase in BAC after cisapride was modest compared with the BAC reached when the same dose of ethanol was ingested on an empty stomach. The corresponding serum paracetamol curves indicated that a faster rate of gastric emptying was the main factor responsible for the differences in ethanol pharmacokinetics.

    Analysis of breath alcohol concentration (BrAC) is a practical and non-invasive method to estimate the BAC and this technique is used worldwide for forensic purposes. The reliability of BrAC measurements in subjects with gastroesophageal reflux disease (GERD) has been questioned. We therefore compared simultaneously obtained breath and venous blood alcohol concentrations in 10 patients with severe GERD scheduled for antireflux surgery. In one of the experiments gastroesophageal reflux was provoked by applying abdominal compression. Although some patients complained of pronounced reflux symptoms the breath instrument readings of BrAC did not deviate from the corresponding BAC in the two test situations, that is, with and without provocation of reflux.

    This thesis has established that measuring alcohol in breath can be used to monitor blood alcohol concentration also in subjects with severe GERD. The relative amount of fat, carbohydrate, or protein in a test meal does not influence the pharmacokinetics of a small dose of ethanol as long as the caloric contents of the meals are similar. The rate of gastric emptying is a major factor determining the bioavailability of orally administered ethanol. Treatment with low-dose ASA (75 mg) delayed gastric emptying and caused a lowering of the peak BAC. The prokinetic drug cisapride, administered under conditions that resemble clinical use, increased the peak BAC by accelerating gastric emptying. However, the drug-induced increase in BAC was much less than the BAC observed after drinking the same dose of ethanol on an empty stomach. H. pylori infection is associated with decreased antral ADH activity related to gastritis. Eradication of H. pylori normalises antral ADH activity within two months.

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    1. Effect of high-fat, high-protein, and high-carbohydrate meals on the pharmacokinetics of a small dose of ethanol
    Åpne denne publikasjonen i ny fane eller vindu >>Effect of high-fat, high-protein, and high-carbohydrate meals on the pharmacokinetics of a small dose of ethanol
    1997 (engelsk)Inngår i: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 44, nr 6, s. 521-526Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Aims To investigate whether the relative amounts of fat, carbohydrate (CHO), or protein in a meal influence the pharmacokinetics of a small dose of ethanol.

    Methods Nine healthy men received ethanol (0.30 g kg−1 body weight) on five occasions in a randomized cross-over fashion. On three occasions the dose of ethanol was consumed within 15 min of eating a standardized breakfast of similar volume and calorific value but containing different amounts of fat, CHO, and protein. On two other occasions the same dose of ethanol was ingested on an empty stomach (overnight fast) or administered by intravenous (i.v.) infusion over 30 min.

    Results The blood-ethanol profiles showed large inter and intraindividual variations, especially when ethanol was ingested after eating food. The peak blood-alcohol concentrations (BAC) were 16.6±4.0, 17.7±7.1, and 13.3±4.0 mg dl−1 (mean±s.d.) after fat, CHO, and protein-rich meals and 30.8±4.3 and 54.3±6.4 mg dl−1 after fasting and i.v. infusion, respectively. The corresponding areas under the concentration-time profiles (AUC) were 1767±549, 1619±760, 1270±406 mg dl−1 min after fat, CHO, and protein-rich meals compared with 3210±527 and 4786±446 mg dl−1  min after fasting and i.v. infusion, respectively. The time required to eliminate ethanol from the blood was shortened by 1–2 h in the fed-state.

    Conclusions Drinking ethanol after eating a meal, regardless of the nutritional composition, decreases the systemic availability of ethanol. Because gastric emptying is slow and more prolonged with food in the stomach, the delivery of ethanol to the duodenum and the liver will be highly variable as will the hepatic clearance of ethanol. Provided that portal venous BAC remains fairly low and ethanol metabolizing enzymes are not fully saturated then part of the dose of ethanol can be cleared by hepatic first-pass metabolism (FPM), as one consequence of Michaelis-Menten elimination kinetics.

    sted, utgiver, år, opplag, sider
    Blackwell Publishing Ltd, 1997
    Emneord
    bioavailability, blood ethanol, first-pass metabolism, food, liver blood flow, macronutrients, pharmacokinetics
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-59761 (URN)71214900001 ()
    Tilgjengelig fra: 2010-09-27 Laget: 2010-09-24 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    2. Low-dose aspirin decreases blood alcohol concentrations by delaying gastric emptying
    Åpne denne publikasjonen i ny fane eller vindu >>Low-dose aspirin decreases blood alcohol concentrations by delaying gastric emptying
    Vise andre…
    1997 (engelsk)Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 53, nr 04-Mar, s. 241-246Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective: To determine if treatment with low-dose aspirin (ASA) influences the bioavailability of orally administered alcohol and to assess whether this is caused by altered gastric emptying as measured by the paracetamol absorption test.

    Methods: In a single-center controlled crossover trial, ten healthy male medical students, aged 20–27 years, participated in two experiments in random order. Both times they took paracetamol (1.5 g together with a standardized breakfast) and drank ethanol (0.3 g/kg) 1 h after eating breakfast. On one drinking occasion, no previous medication was given. The other alcohol session was performed after the subjects had taken 75 mg ASA once daily for 7 days. On both occasions, venous blood samples were obtained at exactly timed intervals for a period of 3.5 h.

    Results: The blood-ethanol profiles showed large interindividual variations for both experiments. After treatment with ASA, the maximum blood-ethanol concentration was distinctly lower in seven subjects, almost unchanged in two subjects and increased in one subject. Overall, a statistically significant decrease in the peak blood-ethanol concentration was observed. The time required to reach peak blood-ethanol levels was somewhat longer after treatment with ASA. Although the areas under the concentration–time profiles were smaller after ASA treatment, these differences were not statistically significant. The concentrations of paracetamol in plasma were lower when ethanol was ingested after treatment with ASA and the areas under the concentration–time curves (0–170 min) were smaller.

    Conclusions: Intake of low-dose ASA (75 mg daily) tends to delay the absorption of a moderate dose of ethanol, which results in lower peak blood-ethanol concentrations and smaller areas under the concentration–time curves. The underlying mechanism seems to be delayed gastric emptying as indicated by the paracetamol absorption test.

    sted, utgiver, år, opplag, sider
    Springer Science Business Media, 1997
    Emneord
    Ethanol - Low-dose aspirin
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-59760 (URN)10.1007/s002280050369 (DOI)71436600013 ()9476038 (PubMedID)
    Tilgjengelig fra: 2010-09-27 Laget: 2010-09-24 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    3. Impact of gastric emptying on the pharmacokinetics of ethanol as influenced by cisapride
    Åpne denne publikasjonen i ny fane eller vindu >>Impact of gastric emptying on the pharmacokinetics of ethanol as influenced by cisapride
    1999 (engelsk)Inngår i: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 48, nr 5, s. 728-732Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Aims To examine the influence of cisapride on the pharmacokinetics of ethanol and the impact of gastric emptying monitored by the paracetamol absorption test.

    Methods Ten healthy male volunteers took part in a cross-over design experiment. They drank a moderate dose of ethanol 0.30 g kg−1 body weight exactly 1 h after eating breakfast either without any prior drug treatment or after taking cisapride (10 mg three times daily) for 4 consecutive days. In a separate study, the same dose of ethanol was ingested on an empty stomach (overnight fast). Paracetamol (1.5 g) was administered before consumption of ethanol to monitor gastric emptying. Venous blood was obtained at 5–10 min intervals for determination of ethanol by headspace gas chromatography and paracetamol was analysed in serum by high performance liquid chromatography (h.p.l.c.).

    Results The maximum blood-ethanol concentration (Cmax ) increased from 3.8±1.7 to 5.6±2.3 mmol l−1 (±s.d.) after treatment with cisapride (95% confidence interval CI on mean difference 0.28–3.28 mmol l−1 ). The area under the blood-ethanol curve (AUC) increased from 6.3±3.5 to 7.9±2.6 mmol l−1 h after cisapride (95% CI −0.74–3.9 mmol l−1 h). The mean blood ethanol curves in the cisapride and no-drug sessions converged at ≈2 h after the start of drinking. Both Cmax and AUC were highest when the ethanol was ingested on an empty stomach (Cmax 9.5±1.7 mmol l−1 and AUC 14.6±1.9 mmol l−1 h), compared with drinking 1 h after a meal and regardless of pretreatment with cisapride.

    Conclusions A small but statistically significant increase in Cmax occurred after treatment with cisapride owing to faster gastric emptying rate as shown by the paracetamol absorption test. However, the rate of absorption of ethanol, as reflected in Cmax and AUC, was greatest after drinking the alcohol on an empty stomach. The cisapride–ethanol interaction probably lacks any clinical or forensic significance.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-25121 (URN)10.1046/j.1365-2125.1999.00080.x (DOI)9554 (Lokal ID)9554 (Arkivnummer)9554 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Reliability of breath-alcohol analysis in individuals with gastroesophageal reflux disease
    Åpne denne publikasjonen i ny fane eller vindu >>Reliability of breath-alcohol analysis in individuals with gastroesophageal reflux disease
    Vise andre…
    1999 (engelsk)Inngår i: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 44, nr 4, s. 814-818Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Gastroesophageal reflux disease (GERD) is widespread in the population among all age groups and in both sexes. The reliability of breath alcohol analysis in subjects suffering from GERD is unknown. We investigated the relationship between breath-alcohol concentration (BrAC) and blood-alcohol concentration (BAC) in 5 male and 5 female subjects all suffering from severe gastroesophageal reflux disease and scheduled for antireflux surgery. Each subject served in two experiments in random order about 1-2 weeks apart. Both times they drank the same dose of ethanol (~0.3 g/kg) as either beer, white wine, or vodka mixed with orange juice before venous blood and end-expired breath samples were obtained at 5-10 min intervals for 4 h. Ah attempt was made to provoke gastroesophageal reflux in one of the drinking experiments by applying an abdominal compression belt, Blood-ethanol concentration was determined by headspace gas chromatography and breath-ethanol was measured with an electrochemical instrument (Alcolmeter SD-400) of a quantitative infrared analyzer (Data-Master). During the absorption of alcohol, which occurred during the first 90 min after the start of drinking, BrAC (mg/210 L) tended to be the same of higher than venous BAC (mg/dL). In the post-peak phase, the BAC al ways exceeded BrAC. Four of the 10 subjects definitely experienced gastric reflux during the study although this did not result in widely deviant BrAC readings compared with BAC when sampling occurred at 5- min intervals. We conclude that the risk of alcohol erupting from the stomach into the mouth owing to gastric reflux and falsely increasing the result of an evidential breath-alcohol test is highly improbable.

    Emneord
    forensic science, alcohol, analysis, blood, breath analysis, disease state, drinking and driving, DUI challenges, gastric reflux
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-25022 (URN)10432616 (PubMedID)9443 (Lokal ID)9443 (Arkivnummer)9443 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    5. Influence of Age, Sex, and Helicobacter pylori Infection Before and After Eradication on Gastric Alcohol Dehydrogenase Activity
    Åpne denne publikasjonen i ny fane eller vindu >>Influence of Age, Sex, and Helicobacter pylori Infection Before and After Eradication on Gastric Alcohol Dehydrogenase Activity
    2001 (engelsk)Inngår i: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 25, nr 4, s. 508-512Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Gastric alcohol dehydrogenase may contribute to the metabolism of orally ingested ethanol and decrease the bioavailability of the drug. The aims of this study were to assess the impact of Helicobacter pylori infection and its eradication on gastric alcohol dehydrogenase activity and to relate the findings to gastric histology. Furthermore, the role of age- and sex-related differences in gastric alcohol dehydrogenase activity were studied.

    Methods: A total of 76 subjects (39 women and 37 men) underwent upper gastrointestinal endoscopy, and biopsies were obtained from the corpus and antrum. The specimens were used for determining gastric alcohol dehydrogenase activity, histological examination, and urease testing. Subjects with H. pylori infection (n= 36) received medication to eradicate the infection, and repeat biopsies were taken 2 and 12 months later.

    Results: No significant difference in gastric alcohol dehydrogenase activity was found between men and women (p > 0.05). Gastric alcohol dehydrogenase activity did not differ significantly between the subjects older than 50 years (n= 39) and those 50 years or younger (n= 37). In subjects with H. pylori infection, gastric alcohol dehydrogenase activity was significantly reduced in the antrum (p < 0.05). After eradication of H. pylori, alcohol dehydrogenase activity in the antrum increased significantly within 2 months (p < 0.01). Antral biopsies with the most pronounced inflammation and histological changes had significantly decreased alcohol dehydrogenase activity (p < 0.05). In contrast, no significant differences were found in corpus.

    Conclusions: H. pylori infection is associated with decreased antral alcohol dehydrogenase activity, which seems to be related to the severity of the inflammatory changes in the mucosa. Eradication of H. pylori normalizes antral alcohol dehydrogenase activity within 2 months.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-24960 (URN)10.1111/j.1530-0277.2001.tb02243.x (DOI)9371 (Lokal ID)9371 (Arkivnummer)9371 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
  • 80.
    Kechagias, Stergios
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Akutkliniken.
    Botella, Sofia
    Petersson, Fredrik
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ericson, Ann-Charlott
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi.
    Expression of vanilloid receptor-1 in epithelial cells of human antral gastric mucosa2005Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, nr 7, s. 775-782Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. Capsaicin, which acts by binding to the vanilloid receptor-1 (VR1), has been shown to give protection against gastric mucosal injury and to enhance healing of gastric ulcers. Although VR1 has recently been reported to be present in non-neural tissues, it is primarily considered to be expressed in nociceptor sensory neurons of small diameter. The aim of the present study was to evaluate the distribution of VR1 immunoreactivity in the normal human gastric mucosa. Material and methods. Ten volunteers underwent gastroscopy and biopsies were obtained from the corpus and the antrum. The specimens were labelled immunohistochemically using polyclonal goat anti-VR1 and evaluated at the light- and electronmicroscopic level. Moreover, post-embedding immunogold labelling was performed and subsequently analysed at the electronmicroscopic level. Results. In the antrum, VR1 immunoreactivity was located in epithelial cells that fulfilled the criteria of endocrine cells of the "open type". These cells were located primarily in the neck region of the antral glands and the labelling was concentrated on the microvilli of these cells. At the ultrastructural level, round granulae with differences in electron density were identified in the basal compartment of the labelled cells. VR1 immunoreactivity was also identified in axon-like structures that were located in the lamina propria, often in close vicinity of vessels, in the corpus as well as in the antrum. Conclusions. VR1-immunoreactivity was evident in antral epithelial cells exhibiting characteristics of endocrine-like cells. This may indicate that the gastroprotective effects of capsaicin, which hitherto have been attributed to primary afferent neurons, at least partly may be explained by an action on specific epithelial cells in the antrum. © 2005 Taylor & Francis.

  • 81.
    Kechagias, Stergios
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Akutkliniken.
    Ekstedt, Mattias
    Linköpings universitet, Institutionen för molekylär och klinisk medicin.
    Mathiesen, UL
    Franzen, L
    New reference interval for ALAT does not identify subclinical liver disease. Lower limit than the proposed should be used for medical considerations!2004Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, s. 2884-2887Artikkel i tidsskrift (Annet vitenskapelig)
  • 82. Kechagias, Stergios
    et al.
    Kechagias, Stergios
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin.
    Kullman, Eric
    Kullman, Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-magtarm.
    Ludvigsson, Johnny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Sjödin, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Almér, Lars-Olof
    Almér, Lars-Olof
    Invärtesmedicin MAS, Malmö.
    En AT-skrivning bör inte enbart ha lätta frågor om vanliga tillstånd!2002Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 100, s. 1739-1739Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 83.
    Kechagias, Stergios
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Akutkliniken.
    Kullman, Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ludvigsson, Johnny
    Sjödin, Ingemar
    Almér, Lars-Olof
    Replik: Samtalskonst och kommunikation efter AT2003Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 100, s. 2466-2467Artikkel i tidsskrift (Annet vitenskapelig)
  • 84. Kinlay, S
    et al.
    Schwartz, G
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Rifai, N
    Leslie, S
    Sasiela, WJ
    Szarek, M
    Libby, P
    Ganz, P
    High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study2003Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 108, nr 13, s. 1560-1566Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background - Inflammation promotes acute coronary syndromes and ensuing clinical complications. Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina, the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown. Methods and Results - We measured C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects with unstable angina or non-Q-wave myocardial infarction were randomized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks. The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome, country, and initial level of marker. All 3 markers were markedly elevated at randomization and declined over the 16 weeks in both treatment groups. Compared with placebo, atorvastatin significantly reduced CRP, -83% (95% CI, -84%, -81%) versus -74% (95% CI, -75%, -71%) (P<0.0001) and SAA, -80% (95% CI, -82%, -78%) versus -77% (-79%, -75%) (P=0.0006) but not IL-6, -55% (95% CI, -57%, -53%) versus -53% (95% CI, -55%, -51%) (P=0.3). Reductions in CRP and SAA were observed in patients with unstable angina and non-Q-wave myocardial infarction, with initial LDL cholesterol <3.2 of =3.2 mmol/L (125 mg/dL), age =65 or <65 years, and in men and women. By 16 weeks, CRP was 34% lower with atorvastatin than with placebo. Conclusions - High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes. This supports the value of early statin therapy in these patients.

  • 85. Kinlay, S
    et al.
    Schwartz, G
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Rifai, N
    Sasiela, W
    Szarek, M
    Ganz, P
    Libby, P
    Effect of atorvastatin on risk of recurrent cardiovascular events after an acute coronary syndrome associated with high soluble CD40 ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study2004Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 110, nr 4, s. 386-391Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background - Patients with acute coronary syndromes have elevated plasma levels of the proinflammatory, prothrombotic cytokine CD40 ligand (sCD40L). Statins inhibit CD40L signaling in vitro, but there are no prospective studies of statins and sCD40L in acute coronary syndromes. Methods and Results - We measured sCD40L in subjects with an acute coronary syndrome enrolled in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects were randomized in this double-blind trial to atorvastatin 80 mg/d or placebo for 16 weeks. Plasma CD40L was measured from 2908 (94%) of 3086 subjects at baseline and 2352 (76%) at 16 weeks. Odds ratios (Ors) and 95% Cis from logistic regression models assessed the risk of recurrent cardiovascular events over 16 weeks (death, nonfatal myocardial infarction, cardiac arrest, and worsening angina requiring rehospitalization) in the placebo group from baseline sCD40L and the effect of atorvastatin on the risk associated with CD40L in all subjects. The effects of atorvastatin on plasma concentrations of CD40L were assessed by Wilcoxon tests. There was a threshold effect, with only high sCD40L (>90th centile) being a risk factor for a recurrent cardiovascular event (OR 1.86, 95% CI 1.25 to 2.77). This risk was abolished by atorvastatin (OR 1.09, 95% CI 0.69 to 1.76), which reduced the risk by 48%. Atorvastatin had only a modest effect on sCD40L (P=0-08). Conclusions - In patients with acute coronary syndromes, atorvastatin abrogated the risk of recurrent cardiovascular events associated with high sCD40L. Early statin therapy after acute coronary syndromes counters the risk associated with elevated sCD40L.

  • 86.
    Kristenson, Margareta
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö. Östergötlands Läns Landsting, FHVC - Folkhälsovetenskapligt centrum, Förebygg.med.
    Kucinskiene, Z
    Bergdahl, Björn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Tagesson, C
    Orth-Gomer, K
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Self-rated health and biological mechanisms: experiences from the LiVicordia study.2000Inngår i: Self-rated health in a European perspective / [ed] Peter Nilsson and Kristina Orth-Gomér, Linköping: Linköpings universitet , 2000, s. 167-175Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 87.
    Kristenson, Margareta
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö. Östergötlands Läns Landsting, FHVC - Folkhälsovetenskapligt centrum, Förebygg.med.
    Lassvik, Claes
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    Bergdahl, Björn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Kucinskiene, Z
    Aizieniene, L
    Ziedén, Bo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Schäfer Elinder, Liselott
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Ultrasound determined carotid and femoral atherosclerosis in Lithuanian and Swedish men: The LiVicordia study2000Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 151, nr 2, s. 501-508Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Coronary heart disease mortality is four times higher in Lithuanian compared to Swedish middle-aged men. Using the same equipment (Acuson XP10 with 5 MHz linear transducer) and staff, we compared the amount of atherosclerosis in carotid and femoral arteries in 100 randomly sampled 50-year-old men in each of the cities Vilnius, Lithuania and Linköping, Sweden. Atherosclerotic plaques were more abundant in Vilnius men compared to Linköping men (53 versus 28% in the common carotid artery, 73 versus 37% in the common femoral artery, P<0.001 for both). Plaques were thicker and more extended in arteries of Vilnius men, and an ultrasound atherosclerosis score was higher in both carotid and femoral arteries (P<0.001 for all). More Vilnius men had a maximal intima-media thickness of the common femoral artery above 1 mm (P<0.005). Stiffness in the common carotid artery was higher in Vilnius men (P<0.001). In a linear regression model of the pooled material, after adjustment for city was made, smoking, systolic blood pressure, low density lipoprotein cholesterol and β-carotene (inversely) significantly contributed to a high total ultrasound score (r2=0.32). These findings show that the higher coronary mortality noted in Lithuanian men goes together with a higher prevalence of early peripheral atherosclerosis.

  • 88.
    Kristenson, Margareta
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Socialmedicin och folkhälsovetenskap. Östergötlands Läns Landsting, Folkhälsovetenskapligt centrum, Folkhälsovetenskapligt centrum.
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Kucinskiene, Zita
    Vilnius University, Lithuania.
    Good self-rated health is related to psychosocial resources and a strong cortisol response to acute stress: The LiVicordia study of middle-aged men2005Inngår i: International Journal of Behavioral Medicine, ISSN 1070-5503, E-ISSN 1532-7558, Vol. 12, nr 3, s. 153-160Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Self-rated health (SRH) is a strong predictor for disease and death. The relations among SRH, psychosocial factors, and cortisol dynamics were tested using pooled data from the LiVicordia study of 50-year-old men in Lithuania (n = 94) and Sweden (n = 89), controlling for effect of residence. SRH was assessed by " How would you assess your own health?" A standardized laboratory stress test included measures of cortisol in serum and saliva. Good SRH related to high scale scores of decision latitude, social support at work, coping, self-esteem, and sense of coherence, to low scores of overcommitment (all p < .01) and vital exhaustion (r = -0.40, p < 0.001), to low concentrations of saliva baseline cortisol (r = -.26, p = .001), and to a strong cortisol response to stress (r = .27, p = .001). Findings that good SRH related to favorable psychosocial characteristics and to a dynamic cortisol stress response indicate a possible explanation for observed lower risk for disease and death in this state. Copyright © 2005 by Lawrence Erlbaum Associates, Inc.

  • 89.
    Kukulski, T
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi.
    Voigt, JU
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi.
    Wilkenshoff, Ursula
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin.
    Strotmann, JM
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi.
    Wranne, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    Hatle, L
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi.
    Sutherland, GR
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi.
    A comparison of regional myocardial velocity information derived by pulsed and color: an in vitro and in vivo stydy2000Inngår i: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 17, s. 639-951Artikkel i tidsskrift (Fagfellevurdert)
  • 90.
    Kullberg, Carin E.
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Long-term glycaemic control and complications in Type 1 diabetes1995Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The impact of long-term glycaemic control, assessed by HbA1c measurements for five years or more, on diabetic retinopathy, nephropathy, and impaired vibration perception threshold was investigated in adult patients with Type 1 diabetes mellitus. Type 1 diabetes was defined as onset of diabetes before the age of 31, with insulin therapy introduced within 6 months from onset, and with no other known cause of insulin deficiency. A comparison of glycated haemoglobin values, as assessed in different long-term studies of the relationship between glycaemic control and diabetic complications was also made.

    High long-term mean HbA1c was shown to be strongly associated to development of proliferative retinopathy and nephropathy, and the severity of background retinopathy and impairment of vibration perception threshold in patients with 5-25 yr duration of diabetes. Patients who developed proliferative retinopathy had a long-tenn mean HbA1, of 8.9% (95% Cl 8.1-9.6%, nonnal range 3.5-5.5% HbA1,), and patients who developed nephropathy had a long-term mean HbA1c of &.8% (95% Cl 7 .8-9.9%) prior to the diagnosis of these complications. Patients with HbA1c >8% also had a relative risk of 6.3 (95% Cl 2.9<RR<l3.9) of having vibration perception threshold (VPT) >l00% above the normal range, and no patient with HbA1c below 6.5% had> 100% elevated VPT.

    Low long-term HbA1c was a beneficial factor for avoidance of retinopathy, but was of less importance to prevent microalbuminuria after more than 20 yr of diabetes. No patient with long-term mean HbA1c above 7.3% avoided retinopathy for such a long period, while patients with normoalbuminuria had HbA1c values in the range 4.6-9.9%.

    Men tended to have more severe lesions than women, without a corresponding gender difference in glycaemic control. Elevated blood pressure was found to be associated with nephropathy, retinopathy, and impaired vibration perception threshold.

    In the comparison of glycated haemoglobin values from different long-term studies of glycaemic control and complications of diabetes, the differences between the highest and lowest results of the same sample were, on average 2% HbA1c. This difference is of the same magnitude as the reported difference in glycaemic control between intensified and regular treatment in interventional studies.

    In conclusion, long-term mean HbA,c is a strong predictor of diabetic complications in the individual patient. Standardisation of HbA1c methods, regular monitoring of HbA1c, and intervention aiming at avoidance of poor glycaemic control is therefore essential.

  • 91. Kurland, L
    et al.
    Melhus, H
    Kahan, T
    Malmquist, K
    Öhman, P
    Nyström, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Hägg, A
    Lind, L
    ACE-gene polymorphism predicts blood pressure response to angiotensin-II receptor blockers in hypertensive patients.2001Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 19, s. 1783-1787Artikkel i tidsskrift (Fagfellevurdert)
  • 92.
    Kurland, Lisa
    et al.
    Internmedicin Uppsala.
    Melhus, Håkan
    Internmedicin Uppsala.
    Karlsson, Julia
    Internmedicin Uppsala.
    Kahan, Thomas
    Internmedicin Danderyd.
    Malmqvist, Karin
    Internmedicin Danderyd.
    Öhman, Peter
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin.
    Nyström, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-endokrin.
    Hägg, Anders
    Internmedicin Uppsala.
    Lind, Lars
    Internmedicin Uppsala.
    Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial2002Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 20, s. 657-663Artikkel i tidsskrift (Fagfellevurdert)
  • 93.
    Landberg, Eva
    et al.
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Rydén, Ingvar
    Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
    Arvidsson, Britt-Marie
    Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
    Ekman, Bertil
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration2007Inngår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 376, nr 1-2, s. 220-225Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    In human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin.

    Methods

    A method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin.

    Results

    The recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (rs = 0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (rs = 0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration.

    Conclusions

    Ultrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.

  • 94.
    Larsson, Hans
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken. Linköpings universitet, Hälsouniversitetet.
    Myocardial ischemia: As a risk indicator after an episode of unstable angina or non-Q-wave myocardial infarction1991Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The diagnostic and prognostic value of different noninvasive tests were evaluated in men below 70 years of age admitted to the coronary care unit (CCU) with unstable coronary artery disease (CAD) i.e unstableangina or non-Q-wave myocardial infarction (Ml). A symptom limited exercise test (ET) was performed before discharge in 740 patients. In subgroups 24 hour ST-recordings were performed in the CCU (n=75),before discharge (n=198) and ambulatory after one month (n=109). A second ET combined with SPECT Tl201 myocardial perfusion imaging was done after one month in 197 patients. Myocardial ischemia was defined as ST-depression > 0.1 m V or according to a model developed for interpretation of SPECTT1201 scintieraphy. All patients were followed one year.

    Patients with myocardial ischemia at the predischargc ET (51 %) had a significantly higher rate of death or MI (18 %) compared to those without (9 %) regardless of simultaneous pain or not. STrccordingin the acute phase or before discharge showed less often myocardial ischemia (23-18 %) than ambulatory during ordinary daily life (33 %). In the same group of patients myocardial ischemia was more often elicited by a predischarge ET (52%). The majority of patients with ST-depression at ST-recordings also showed myocardial ischemia at the predischarge ET. Myocardial ischemia at the ST-rccording beforedischarge identified a small group (18 %) of patients with a more severe prognosis- 23% rvn or death after 3 months compared to 7 % in the patients without this observation. In a logistic regression analysis ST-depression at the predischarge ST-recording was the only significant predictor of MI or death during the first three months while myocardial ischemia at the predischarge ET became the only significant indicator of long term outcome. In a comparison between the predischarge and the one month ET 83 % of patients showed the same response regarding occurrence of ST -depression. The rate of MI or death during the first month were more common in patients with (8.3 %) than without (3.7 %) myocardial ischemia at the predischarge ET and so was the occurrence of future symptoms of severe angina. Regarding the following 11 months, myocardial ischemia at the predischarge or the one month ET had the same prognostic importance for MI, death or severe angina. SPECT Tl 201 imaging at ET improved the separation between high and low risk patients. If both SPECT Tl 201 imaging and the ECG response showed signs of ischemia (37 %) the risk of future cardiac events was markedly elevated- 17 % MI or death compared to 7 % in patients without this finding. Thus, risk stratification of men after an episode of unstable coronary artery disease can be performed already before discharge. Patients with continuing myocardial ischemia despite treatment should be considered for rcvascularisation whether or not the ischemia is associated with pain.

  • 95.
    Li, Wei
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Oxidative stress, macrophages, iron, and atherosclerosis1997Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Macrophages have a great capacity to take up exogenous material, such as oxidatively modified low density lipoproteins (oxLDL) and different sources of iron containing structures. OxLDL is taken up into macrophage lysosomes by receptor-mediated endocytosis, but poorly degraded, resulting in foam-cell formation. The foam cell formation and the cytotoxicity of oxLDL to several arterial wall cells might contribute to atherogenesis. The iron sequestrated by macrophages could potentially become cytotoxic, particularly following intralysosomal accumulation of low-molecular weight iron in a redox-active form, and under conditions of oxidative stress. Following autophagocytosis, endogenous ferritin/apoferritin may serve as chelators of such lysosomal iron and counteract the occurrence of iron-mediated intra-lysosomal oxidative reactions.

    In the present study, we estimated the influence of oxLDL on lysosomal enzyme activity, lysosomal membrane stability, and the modulation of these cellular characteristics by high density lipoprotein (HDL) and vitamin E (vit-E). We also examined iron-stimulated ferritin synthesis, and the effects of exogenously added apoferritin on cells and lysosomal membrane stability following oxidative stress. Human monocyte-derived macrophages and J-774 cells were used in the study. The activities of the lysosomal enzymes, cathepsin-L and N-acetyl-ß-glucosarninidase (NAßGase), were biochemically assayed on cellular fractions. The lysosomal integrity was estimated by an acridine orange (AO) vital staining test as well as by immunocytochemical cathepsin-D demonstration. Cellular ferritin was assayed by ELISA, and lysosomal iron was demonstrated by autometallography and transmission electron microscopy.

    We found that the total activities of NAßGase and cathepsin-L were significantly decreased, whereas their relative cytosolic activities were enhanced after oxLDL-exposure. Labilization of the lysosomal membranes was further proven by a decreased lysosomal AO-uptake and a relocation to the cytosol of cathepsin-D. as estimated by light- and electron microscopic immunocytochemistry. HDL and vit-E diminished the cytotoxicity of oxLDL by decreasing the lysosomal damage. The synthesis and accumulation of ferritin in HMDM are responses to the iron-exposure, but ferritin is not efficient enough to protect the lysosomes from oxidative stress. Endocytosed apoferritin acts as a stabilizer of the acidic vacuolar compartment of iron-loaded macrophages.

  • 96.
    Li, Wei
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi.
    Hellsten, Anna
    Linköpings universitet, Institutionen för biomedicin och kirurgi.
    Jacobsson, Leif
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Blomqvist, Henrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin.
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Yuan, Xi Ming
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi.
    Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma of hyperlipidaemic rabbits2004Inngår i: Journal of Molecular and Cellular Cardiology, ISSN 0022-2828, E-ISSN 1095-8584, Vol. 37, nr 5, s. 969-978Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The composition of atherosclerotic plaques, not just macroscopical lesion size, has been implicated in their susceptibility to rupture and the risk of thrombus formation. By focusing on the quality of lipids, macrophages, apoptosis, collagen, metalloproteinase expression and plaque integrity, we evaluated the possible anti-atherosclerotic effect of the antioxidants α-tocopherol and astaxanthin in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one WHHL rabbits were divided into three groups and were fed a standard diet, as controls (N =10), or a standard diet with the addition of 500 mg α-tocopherol per kg feed (N =11) or 100 mg astaxanthin per kg feed (N =10) for 24 weeks. We found that both antioxidants, particularly astaxanthin, significantly decreased macrophage infiltration in the plaques although they did not affect lipid accumulation. All lesions in the astaxanthin-treated rabbits were classified as early plaques according to the distribution of collagen and smooth muscle cells. Both antioxidants also improved plaque stability and significantly diminished apoptosis, which mainly occurred in macrophages, matrix metalloproteinase three expressions and plaque ruptures. Although neither antioxidant altered the positive correlations between the lesion size and lipid accumulation, the lesion size and apoptosis were only positively correlated in the control group. Astaxanthin and α-tocopherol may improve plaque stability by decreasing macrophage infiltration and apoptosis in this atherosclerotic setting. Apoptosis reduction by α-tocopherol and astaxanthin may be a new anti-atherogenic property of these antioxidants. © 2004 Elsevier Ltd. All rights reserved.

  • 97.
    Li, Wei
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Yuan, Xi Ming
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Brunk, Ulf
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Uptake of Oxidized LDL by Macrophages Results in Partial Lysosomal Enzyme Inactivation and Relocation1998Inngår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 18, nr 2, s. 177-84Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cytotoxicity of oxidized LDL (oxLDL) to several types of artery wall cells might contribute to atherosclerosis by causing cell death, presumably by both apoptosis and necrosis. After its uptake into macrophage lysosomes by receptor-mediated endocytosis, oxLDL is poorly degraded, resulting in ceroid-containing foam cells. We studied the influence of oxLDL on lysosomal enzyme activity and, in particular, on lysosomal membrane stability and the modulation of these cellular characteristics by HDL and vitamin E (vit-E). Unexposed cells and cells exposed to acetylated LDL (AcLDL) were used as controls. The lysosomal marker enzymes cathepsin L and N-acetyl-β-glucosaminidase (NAβGase) were biochemically assayed in J-774 cells after fractionation. Lysosomal integrity in living cells was assayed by the acridine orange (AO) relocation test. Cathepsin D was immunocytochemically demonstrated in J-774 cells and human monocyte-derived macrophages. We found that the total activities of NAβGase and cathepsin L were significantly decreased, whereas their relative cytosolic activities were enhanced, after oxLDL exposure. Labilization of the lysosomal membranes was further proven by decreased lysosomal AO uptake and relocation to the cytosol of cathepsin D, as estimated by light and electron microscopic immunocytochemistry. HDL and vit-E diminished the cytotoxicity of oxLDL by decreasing the lysosomal damage. The results indicate that endocytosed oxLDL not only partially inactivates lysosomal enzymes but also destabilizes the acidic vacuolar compartment, causing relocation of lysosomal enzymes to the cytosol. Exposure to AcLDL resulted in its uptake with enlargement of the lysosomal apparatus, but the stability of the lysosomal membranes was not changed.

  • 98. Liljedahl, U
    et al.
    Karlsson, J
    Melhus, H
    Kurland, L
    Lindersson, M
    Kahan, T
    Nyström, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Lind, L
    Syvanen, AC
    A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response2003Inngår i: Pharmacogenetics, ISSN 0960-314X, E-ISSN 1473-561X, Vol. 13, nr 1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We aimed to develop a microarray genotyping system for multiplex analysis of a panel of single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in blood pressure regulation, and to apply this system in a pilot study demonstrating its feasibility in the pharmacogenetics of hypertension. A panel of 74 SNPs in 25 genes involved in blood pressure regulation was selected from the SNP databases, and genotyped in DNA samples of 97 hypertensive patients. The patients had been randomized to double-blind treatment with either the angiotensin II type 1 receptor blocker irbesartan or the ▀1-adrenergic receptor blocker atenolol. Genotyping was performed using a microarray based DNA polymerase assisted 'minisequencing' single nucleotrde primer extension assay with fluorescence detection. The observed genotypes were related to the blood pressure reduction using stepwise multiple regression analysis. The allele frequencies of the selected SNPs were determined in the Swedish population. The established microarray-based genotyping system was validated and allowed unequivocal multiplex genotyping of the panel of 74 SNPs in every patient. Almost 7200 SNP genotypes were generated in thestudy. Profiles of four or five SNP-genotypes that may be useful as predictors of blood pressure reduction after antihypertensive treatment were identified. Our results highlight the potential of microarray-based technology for SNP genotyping in pharmacogenetics. Pharrnacogenetics 13:7-17 ⌐ 2003 Lippincott Williams & Wilkins.

  • 99. Lind, S
    et al.
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Eriksson, M
    Rudling, M
    Eggertsen, G
    Angelin, B
    Autosomal recessive hypercholesterolaemia: Normalization of plasma LDL cholesterol by ezetimibe in combination with statin treatment2004Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 256, nr 5, s. 406-412Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Severe hereditary hypercholesterolaemia is most frequently due to familial hypercholesterolaemia (FH), caused by mutations in the LDL receptor (LDLR) gene. However, a phenotype very similar to FH may also be caused by defects in other genes like the genes for apolipoprotein (apo) B-100 or autosomal recessive hypercholesterolaemia (ARH). Subject. An 8-year-old male of Lebanese origin was diagnosed with severe hypercholesterolaemia and extensive cutaneous and tendon xanthomas. Plasma LDL cholesterol before treatment was 17 mmol L-1, whilst parents and both siblings had normal levels. Diagnosis. Degradation of 125I-labelled LDL in blood lymphocytes was reduced, but not abolished. Sequencing analysis of the LDLR and apoB-100 genes were negative, whilst a splice acceptor mutation in intron 1 (IVS 1 - 1G>C) was detected in the ARH gene. The patient was homozygous for the mutation, whilst the parents were heterozygous. These findings were in agreement with a diagnosis of ARH. Treatment and clinical course. Monthly LDL apheresis and atorvastatin 120 mg daily reduced LDL cholesterol preapheresis level to 4.8 mmol L-1. When ezetimibe was given 10 mg day-1 in combination with rosuvastatin 80 mg day-1, LDL cholesterol was further lowered to 1.6 mmol L-1, which made apheresis unnecessary. Cutaneous and tendon xanthomas disappeared completely and the intima-media thickness of the common carotid arteries decreased. At age 23 he developed a small myocardial infarction. Conclusion. ARH should be considered in cases of severe hypercholesterolaemia with a pattern of recessive inheritance. Combination therapy with high-dose statin and ezetimibe seems to be the treatment of choice in ARH and may reduce or eliminate the need for LDL apheresis treatment.

  • 100.
    Lindberg, Eva
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Crohn's disease: Studies on epidemiology, twins, aetiological factors and clinical course with special reference to smoking1992Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In an epidemiological study of the incidence of Crohn's disease in Orebro county during the 25-year period 1963-1987, the mean annual incidence was 6.1/105 inhabitants. During the first five year period the mean incidence was 4.3 but during the following four quinquennia the incidence was stable at around 6.6/105 inhabitants. The point prevalence at 31/12 1987 was 146/105, with male to female ratio of 1:1.15. The mean age at diagnosis increased from 23 to 32 years. No cohort more prone to develop the disease was found. Of the 246 incidence cases 5 patients had died of Crohn's disease.

    The genetic influence was analysed in 18 monozygotic and 26 dizygotic twin palrs with Crohn's disease. Eight of the monozygotic palrs were concordant for the disease but only one of the dizygotic pairs. The proband concordance rate was 58.3% for monozygotic twins and the heritability of liability (r) 1.0. The corresponding figures for dizygotic twins were 3.9% and 0.47. When comparing with ulcerative colitis the heritability was found to be significantly stronger in Crohn's disease.

    A case-control study of smoking habits in 144 patients and 259 matched population controls showed that smoking doubled the risk of aquiring Crohn's disease. In former smokers a non-significant increased risk was observed.

    The effects of smoking on the localization and course of Crohn's disease was evaluated in 231 patients. Patients with high life time tobacco exposure (>150 cig.years) had small bowel disease more often than patients with low life time exposure. Heavy smokers(> 10 cig./day) had a slightly increased risk to be operated at least once, odds ratios after 5 and 10 years of follow up for heavy smokers compared to never smokersbeing 1.14 and 1.24 respectively. The risk for heavy smokers to be operated twice or more was even higher after 10 years offollow up, the odds ratio being 1.79. The accumulated number of fistulae and/or abscesses was higher in smokers than never smokers.

    Twenty-six monozygotic twin pairs with inflammatory bowel disease and 52 healthy controls were investigated for serum antibodies (IgA, IgG, IgM) against ovalbuntin, betalactoglobulin, gliadin, whole yeast (Saccharomyces cerevisiae) and mannan. Twins that had developed Crohn's disease displayed higher titers of all three antibodies towards mannan, and also higher IgA towards yeast. Their healthy twin hadhigher IgA to mannan and yeast. These results suggest that yeast cell wall material for instance mannan or some antigen rich in mannose and cross reacting with mannan might play an aetiological role in Crohn's disease.

    Conclusion: The incidence of Crohn's disease has been stable during the last 20 years. The genetic influence is important. Smoking increases the risk of aquiring Crohn's disease and heavy smokers have a worse outcome of the disease. Patients with high life time tobacco exposure more often have small bowel disease. Mannan or agents cross-reacting with mannan may play a role in the pathogenesis of the disease. However, not even similar smoking and dietary (as ntirrored by dietary antibodies) habits in identical twins are sufficient to cause disease. Additional factors are needed.

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