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  • 1.
    Aalto, Anne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sjoewall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Davidsson, Leif
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Smedby, Örjan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 7, p. 755-762Article in journal (Refereed)
    Abstract [en]

    Background: Borrelia infections, especially chronic neuroborreliosis ( NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. Purpose: To evaluate brain magnetic resonance imaging ( MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. Material and Methods: Sixteen well- characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- ( with and without gadolinium), T2-, and diffusion- weighted imaging plus fluid- attenuated inversion recovery ( FLAIR) imaging were used. Results: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls ( no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients ( rho=0.83, P < 0.01) and in controls ( rho=0.61, P < 0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2- weighted imaging. Conclusion: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.

  • 2.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Karlberg, Bengt E.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Holm, Ann-Charlotte
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Salivary cortisol: an alternative to serum cortisol determinations in dynamic function tests1998In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 36, no 4, p. 215-222Article in journal (Refereed)
    Abstract [en]

    Salivary cortisol was measured as an alternative to serum cortisol as a marker for adrenocortical function following insulin tolerance test, corticotropin-releasing-hormone stimulation and adreno-corticotrophic hormone stimulation. During insulin tolerance test and corticotropin-releasing-hormone stimulation adreno-corticotrophic hormone was also measured. The tests were performed on healthy control subjects as well as on patients under investigation for various disturbances in the hypothalamic-pituitary-adrenocortical axis (insulin tolerance test: 3 controls on two occasions and 14 patients; corticotropin-releasing-hormone stimulation: 4 controls and 18 patients; adreno-corticotrophic hormone stimulation: 6 controls and 10 patients). Five patients underwent both insulin tolerance test and corticotropin-releasing-hormone stimulation. Using criteria for adequate cortisol response in serum, the patients were classified as good or poor responders. In 42 of the 45 tests performed the same conclusion as to cortisol status was drawn when based on serum and salivary cortisol responses. In healthy subjects and good responders the mean cortisol relative increase was greater in saliva than in serum in all three tests (p < 0.05). Characteristic of the results for the insulin tolerance test was a significant initial mean decrease (p < 0.05), not found in serum, and the highest observed salivary cortisol value was delayed for at least 30 minutes compared to that in serum. Plasma adreno-corticotrophic hormone correlated significantly with the cortisol concentrations determined 15 minutes later in serum (r = 0.54–0.64) and in saliva (r = 0.76–0.85). The more pronounced cortisol response in saliva than in serum and its closer correlation with adreno-corticotrophic hormone offer advantages over serum cortisol, suggesting salivary cortisol measurement may be used as an alternative parameter in dynamic endocrine tets.

  • 3.
    Abildgaard, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Aaro, Stig
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine.
    Lisander, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Limited effectiveness of intraoperative autotransfusion in major back surgery2001In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 18, no 12, p. 823-828Article in journal (Refereed)
    Abstract [en]

    Background and objective: The efficiency of intraoperative autotransfusion in scoliosis surgery is poorly known but needs to be evaluated, not least because of the large blood losses in these patients. This is a retrospective analysis of transfusion requirements of 43 such patients. Methods: Records from 43 patients were studied. During surgery, the shed blood was salvaged and washed in an autotransfusion device (AT1000 Auto-transfusion Unit«) and a suspension of red cells was reinfused. Results: Fifty-eight per cent of the intraoperative blood loss was salvaged. The total blood loss during the patients' hospital stay was calculated from the haemoglobin balance, 24% of this loss was salvaged by the device. Moreover, 36 of the patients needed allogeneic blood transfusion. Conclusion: The efficiency of the autotransfusion device was relatively low in relation to the total extravasation, mainly because the postoperative blood loss is substantial.

  • 4.
    Abrahams, M
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology.
    Eriksson, H
    Björnström, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Eintrei, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Effects of propofol on extracellular acidification rates in primary cortical cell cultures: application of silicon microphysiometry to anaesthesia.1999In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 83, p. 567-569Article in journal (Refereed)
  • 5.
    Abrahams, M
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Oscarsson, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Sundqvist, Tommy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    The effects of human burn injury on urinary nitrate excretion. 1999In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 25, p. 29-33Article in journal (Refereed)
  • 6.
    Adolfsson, Per
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Regulatory importance of cyclic nucleotides in smooth muscle growth of the urogenital tract2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Smooth muscle hyperplasia/hypertrophy is, if not responsible for, so at least involved in those diseases, which impair life quality for most people in today's society.

    This thesis, presents a pharmacological investigation, related to the regulatory role of cyclic nucleotides, of smooth muscle hyperplasia/hypeitrophy in human uterine leiomyoma and benign prostate hyperplasia (BPH).

    Four main aspects, with cAMP as a connecting thought, have been analyzed, namely expression and characterization of the adrenergic receptors (AR), determination of adenylyl cyclase (AC)- and phosphodiesterase (PDE)-activity, and finally the connection between mentioned issues and proliferation of cultured smooth muscle cells (smc).

    In the frrst paper, characterization of the a 2-adrenergic receptor (az-AR) subtypes in human myometrium at term pregnancy was examined by combining radioligand binding-studies with reverse transcriptase-polymerase chain reaction (RT-PCR). Results demonstrated a significant eo-expression of α2A and α2B, and a weak indication of the α2C-AR, which however was identified at the mRNA level by the RT-PCR analysis.

    In the next investigatio~ smooth muscle tissue of human uterine leiomyoma (benign smooth muscle tumor) was compared with surrounding myometrial tissue (control). The expression of AR, AC- and PDE-activity was analyzed, as well as the effect of cAMP with respect to growth regulation of cultured leiomyoma smc. Primarily, a significantly reduced ß2-AR expression and AC-activity was detected in leiomyoma compared to control tissue, whereas the PDE-activity was approximately 100% higher. In addition, the α2-AR population in leiomyoma was slightly increased. When cultured leiomyoma smc was treated with cAMP increasing agents as forskolin, an AC stimulating agent, or papaverin, a general PDE inhibitor, a considerable inhibition of DNA replication and protein synthesis was obtained.

    In the thh·d paper, a proliferation study was made on cultured benign prostate hyperplasia smc, were the mitogen effect of lysophosphatidic acid (LPA) and cAMP/cGMP increasing agents was investigated. LPA generated a dose-dependent mitogen response, which was efficiently inhibited, both by forskolin, and by papaverin. In addition, sildenafil (Viagra®), which serve as a potent and selective PDE5 inhibitor, also decreased the LPA mediated growth promotion in a dose dependent manner.

    The last study, demonstrate primarily the expression pattem of LPA receptors (Edg) in BPH smc. Further, the intracellular cAMP changes in LPA stimulated BPH smc and the proliferative effect of the LPA analogue sphingosine 1-phosphate (SIP) was considered. First, all Edg was identified with exception of Edg6. Moreover, the cAMP level was unchanged by LPA per se, whereas co-incubation with forskolin generated a rapid and transient response. Further, SIP generated a divergent response including a LPA equivalent mitogen effect at low concentrations whereas inhibition of DNA replication was obtained at higher concentrations.

    In summary, this project demonstrates that cyclic nucleotides inhibit smooth muscle hyperplasia/hypertrophy in the luogenital tract. These results also suggest that manipulation of cyclic nucleotide level using tissue specific PDE inhibitors might constitute a new therapeutic approach for hyperplasia/hypertrophy related diseases in the urogenital tract.

    List of papers
    1. Characterization of α2-Adrenoceptor Subtypes in Pregnant Human Myometrium
    Open this publication in new window or tab >>Characterization of α2-Adrenoceptor Subtypes in Pregnant Human Myometrium
    1998 (English)In: Gynecologic and Obstetric Investigation, ISSN 0378-7346, E-ISSN 1423-002X, Vol. 45, no 3, p. 145-150Article in journal (Refereed) Published
    Abstract [en]

    The aim of the present investigation was to determine which subtypes of the α2-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [3H]rauwolscine to human myometrial membranes was specific and of high affinity with Kd of 2.8 ± 0.6 nM and Bmax of 95 ± 5 fmol/mg protein. Results from competition for the binding of [3H]rauwolscine using subtype-selective ligands, oxymetazoline (α2A-subptype), chlorpromazine (α2B-subtype) and prazosin (α2B-α2C-subtype), suggested that the α2A- and α2B-subtypes are being co-expressed. In order to examine if also the α2C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the α2A- and α2B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the α2C-subtype also is being expressed. The expression of α2C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies.

    In conclusion, our results suggest that all three subtypes of α2-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that α2-expression is dominated by the α2A-subtype.

    Keywords
    α2-Adrenergic receptors, Subtype, Myometrium, Human, Pregnancy, [3H]rauwolscine, Reverse transcription-polymerase chain reaction
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80081 (URN)10.1159/000009944 (DOI)
    Available from: 2012-08-20 Created: 2012-08-20 Last updated: 2017-12-07Bibliographically approved
    2. Changes in β2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas
    Open this publication in new window or tab >>Changes in β2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas
    2000 (English)In: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 6, no 9, p. 835-842Article in journal (Refereed) Published
    Abstract [en]

    Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of α2- and β2-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the α22-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in β2-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through β2-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25070 (URN)10.1093/molehr/6.9.835 (DOI)9500 (Local ID)9500 (Archive number)9500 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    3. Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: Sildenafil and papaverin generate inhibition
    Open this publication in new window or tab >>Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: Sildenafil and papaverin generate inhibition
    2002 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 51, no 1, p. 50-58Article in journal (Refereed) Published
    Abstract [en]

    Background The endogenous substance lysophosphatidic acid (LPA) has been found to generate proliferation of cultured smooth muscle cells (SMC). Therefore, the effect of LPA on human benign prostate hyperplasia (BPH) could be of interest.

    Methods The proliferative effect of LPA on cultured human prostatic SMC from specimens obtained at trans-urethral resection of the prostate (TURP) because of BPH, was analyzed by [3H]-thymidine and [35S]-methionine incorporation. In addition, LPA stimulated BPH SMC were treated with papaverin, forskolin, sildenafil or zaprinast, well known to increase the intracellular level of cAMP or cGMP.

    Results LPA produced a dose-dependent increase in BPH SMC, both regarding DNA- and protein-synthesis with EC50 values of 3 and 10 μM, respectively. Furthermore, both papaverin, a general phosphodiesterase inhibitor regarding cAMP hydrolyzes, and forskolin, an adenylyl cyclase stimulating agent, inhibited the LPA-stimulated DNA replication in a dose dependent manner with IC50  = 2.5, and 0.35 μM, respectively. cGMP increasing agents, such as the NO-donors SIN-1 and SNAP, produced a weak anti-proliferative response. However, both phosphodiesterase 5 inhibitors sildenafil (Viagra®) and zaprinast efficiently blocked DNA replication. In addition, when the protein synthesis was examined, we found that the LPA response was significantly inhibited by forskolin and papaverin.

    Conclusions The major conclusion of this investigation is that the endogenous serum component LPA, is able to promote human BPH SMC growth. In addition, our study indicates that cyclic nucleotides can inhibit this effect. Future clinical studies will be needed to determine if different specific phosphodiesterase inhibitors per se or in combination could represent a new therapeutic possibility for the treatment of BPH.

    Keywords
    BPH, SMC, hyperplastic, PDE, AC, cAMP, cGMP, [H-3]-thymidine, [S-35]-methionine, proliferation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-47887 (URN)10.1002/pros.10077 (DOI)
    Note
    On the day of the defence day the status of this article was submitted.Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    4. Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cells
    Open this publication in new window or tab >>Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cells
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The endogenous phospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both known to generate a Vvide variety of effects in various cell systems by the endothelial differentiation gene (Edg) receptor family, including 7 different G-protein coupled Edg receptors.

    In this study, expression of LPA- and SlP Edg receptors was examined, and so was the effect with respect to proliferation on cultured BPH smooth muscle cells smc. Mmeover, theresponse on cAMP levels was examined. Finally, a potential link between activation of the MAP kinase cascade and the LPA stimulated proliferation was investigated.

    First, the RT-PCR analysis of the Edg receptors in BPH smc, demonstrated a heterogeneous expression including all receptors except the Edg6 subtype. Further, in contrast to LPA, the mitogen effect of SIP, demonstrated a concentration-dependent biphasic response, including stimulation below 1μM, whereas inhibition was obtained at higher concentrations. Forskolin induced a rapid and transient cAMP response in LPA stimulated cells, with a peak-value after 3 minutes. After 15 minutes the cAMP level had retmned to base-line level. However a gradual increase to 15% of maximum value was obtained after additional 30 minutes, and thereafter a gradual reduction was observed. The mentioned antiproliferative response generated by SIP could not be conelated to an intracellular cAMP increase. Finally, when the LPA treated smc was co-incubated with the MAPK kinase inhibitor PD98059 (10 μM) the mitogen response was eliminated.

    The cAIVIP increase, which was induced by forskolin, corresponds with mentioned antiproliferative effect whereas a similar con-elation was not obtained regarding SIP. The intracellular signal mechanisms triggered by LPA and S1P in BPH smc remain to be further investigated.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80084 (URN)
    Available from: 2012-08-20 Created: 2012-08-20 Last updated: 2012-08-20Bibliographically approved
  • 7.
    Adolfsson, Per
    et al.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Ahlstrand, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences.
    Svensson, Samuel
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: Sildenafil and papaverin generate inhibition2002In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 51, no 1, p. 50-58Article in journal (Refereed)
    Abstract [en]

    Background The endogenous substance lysophosphatidic acid (LPA) has been found to generate proliferation of cultured smooth muscle cells (SMC). Therefore, the effect of LPA on human benign prostate hyperplasia (BPH) could be of interest.

    Methods The proliferative effect of LPA on cultured human prostatic SMC from specimens obtained at trans-urethral resection of the prostate (TURP) because of BPH, was analyzed by [3H]-thymidine and [35S]-methionine incorporation. In addition, LPA stimulated BPH SMC were treated with papaverin, forskolin, sildenafil or zaprinast, well known to increase the intracellular level of cAMP or cGMP.

    Results LPA produced a dose-dependent increase in BPH SMC, both regarding DNA- and protein-synthesis with EC50 values of 3 and 10 μM, respectively. Furthermore, both papaverin, a general phosphodiesterase inhibitor regarding cAMP hydrolyzes, and forskolin, an adenylyl cyclase stimulating agent, inhibited the LPA-stimulated DNA replication in a dose dependent manner with IC50  = 2.5, and 0.35 μM, respectively. cGMP increasing agents, such as the NO-donors SIN-1 and SNAP, produced a weak anti-proliferative response. However, both phosphodiesterase 5 inhibitors sildenafil (Viagra®) and zaprinast efficiently blocked DNA replication. In addition, when the protein synthesis was examined, we found that the LPA response was significantly inhibited by forskolin and papaverin.

    Conclusions The major conclusion of this investigation is that the endogenous serum component LPA, is able to promote human BPH SMC growth. In addition, our study indicates that cyclic nucleotides can inhibit this effect. Future clinical studies will be needed to determine if different specific phosphodiesterase inhibitors per se or in combination could represent a new therapeutic possibility for the treatment of BPH.

  • 8.
    Adolfsson, Per
    et al.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Haug, Ingrid
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Svensson, Samuel
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Changes in β2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas2000In: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 6, no 9, p. 835-842Article in journal (Refereed)
    Abstract [en]

    Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of α2- and β2-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the α22-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in β2-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through β2-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.

  • 9.
    Adolfsson, Per I.
    et al.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Ahlstrand, Christer
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Hultgren, Sitti
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Svensson, Samuel P. S.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cellsManuscript (preprint) (Other academic)
    Abstract [en]

    The endogenous phospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both known to generate a Vvide variety of effects in various cell systems by the endothelial differentiation gene (Edg) receptor family, including 7 different G-protein coupled Edg receptors.

    In this study, expression of LPA- and SlP Edg receptors was examined, and so was the effect with respect to proliferation on cultured BPH smooth muscle cells smc. Mmeover, theresponse on cAMP levels was examined. Finally, a potential link between activation of the MAP kinase cascade and the LPA stimulated proliferation was investigated.

    First, the RT-PCR analysis of the Edg receptors in BPH smc, demonstrated a heterogeneous expression including all receptors except the Edg6 subtype. Further, in contrast to LPA, the mitogen effect of SIP, demonstrated a concentration-dependent biphasic response, including stimulation below 1μM, whereas inhibition was obtained at higher concentrations. Forskolin induced a rapid and transient cAMP response in LPA stimulated cells, with a peak-value after 3 minutes. After 15 minutes the cAMP level had retmned to base-line level. However a gradual increase to 15% of maximum value was obtained after additional 30 minutes, and thereafter a gradual reduction was observed. The mentioned antiproliferative response generated by SIP could not be conelated to an intracellular cAMP increase. Finally, when the LPA treated smc was co-incubated with the MAPK kinase inhibitor PD98059 (10 μM) the mitogen response was eliminated.

    The cAIVIP increase, which was induced by forskolin, corresponds with mentioned antiproliferative effect whereas a similar con-elation was not obtained regarding SIP. The intracellular signal mechanisms triggered by LPA and S1P in BPH smc remain to be further investigated.

  • 10.
    Adolfsson, Per I.
    et al.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Dahle, Lars Olav
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Svensson, Samuel P. S.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Characterization of α2-Adrenoceptor Subtypes in Pregnant Human Myometrium1998In: Gynecologic and Obstetric Investigation, ISSN 0378-7346, E-ISSN 1423-002X, Vol. 45, no 3, p. 145-150Article in journal (Refereed)
    Abstract [en]

    The aim of the present investigation was to determine which subtypes of the α2-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [3H]rauwolscine to human myometrial membranes was specific and of high affinity with Kd of 2.8 ± 0.6 nM and Bmax of 95 ± 5 fmol/mg protein. Results from competition for the binding of [3H]rauwolscine using subtype-selective ligands, oxymetazoline (α2A-subptype), chlorpromazine (α2B-subtype) and prazosin (α2B-α2C-subtype), suggested that the α2A- and α2B-subtypes are being co-expressed. In order to examine if also the α2C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the α2A- and α2B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the α2C-subtype also is being expressed. The expression of α2C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies.

    In conclusion, our results suggest that all three subtypes of α2-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that α2-expression is dominated by the α2A-subtype.

  • 11.
    Agvall, Björn
    et al.
    Linköping University, Department of Department of Health and Society, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland.
    Borgquist, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Foldevi, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Cost of heart failure in Swedish primary healthcare2005In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 23, p. 227-232Article in journal (Refereed)
    Abstract [en]

    Objectives. To calculate the cost for patients with heart failure (HF) in a primary healthcare setting. Design. Retrospective study of all available patient data during a period of one year. Setting. Two healthcare centers in Linköping in the southeastern region of Sweden, covering a population of 19 400 inhabitants. Subjects. A total of 115 patients with a diagnosis of HF. Main outcome measures. The healthcare costs for patients with HF and the healthcare utilization concerning hospital days and visits to doctors and nurses in hospital care and primary healthcare. Results. The mean annual cost for a patient with HF was SEK 37 100. There were no significant differences in cost between gender, age, New York Heart Association functional class, and cardiac function. The distribution of cost was 47% for hospital care, 22% for primary healthcare, 18% for medication, 5% for nursing home, and 6% for examinations. Conclusion. Hospital care accounts for the largest cost but the cost in primary healthcare is larger than previously shown. The total annual cost for patients with HF in Sweden is in the range of SEK 5.0–6.7 billion according to this calculation, which is higher than previously known.Read More: http://informahealthcare.com/doi/abs/10.1080/02813430500197647

  • 12.
    Agvall, Björn
    et al.
    Linköping University, Department of Department of Health and Society, General Practice. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Patients in primary health care diagnosed and treated as heart failure, with special reference to gender differences2001In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 19, no 1, p. 14-19Article in journal (Refereed)
    Abstract [en]

    Objective - The aim of the present study was to describe patients considered to have had heart failure (HF), or were being treated for HF, in a defined area in primary health care, e.g. diagnostic procedures, aetiologic diseases and management, and to evaluate whether there is a difference between the genders. Design - Descriptive retrospective investigation. Setting - ┼tvidaberg community situated in southeast Sweden, 12 400 inhabitants. Patients - 256 patients treated for symptomatic HF. Main outcome measures - Prevalence, aetiology, diagnostic procedures and management of HF and differences between the genders. Results - The diagnosis of HF was based on an objective evaluation of cardiac function in only 31% of the patients. Ischaemic heart disease (IHD) was the predominant associated disease, followed by hypertension. Therapy included diuretics (84%), angiotensin converting enzyme (ACE) inhibitors (56%) and digoxin (40%). Only 52% had optimal doses of ACE inhibitors. Women had a significantly higher mean age and their diagnoses were based on an objective diagnostic test (echocardiography) in only 20%. Women were prescribed ACE inhibitors to a lesser extent (43%) than men (64%) and with a lower optimal dose (44% versus 56% in men). Conclusion - There is still room for improvement in the management of HF in primary health care, especially in women, where the diagnosis is not generally based on an objective evaluation of cardiac function and where the treatment to a lesser extent than in men includes ACE inhibitors.

  • 13.
    Ahlgren, Ewa
    Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery. Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Cerebral complications after cardiac surgery2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cerebral injuty remains a major cause of morbidity and mortality after cardiac surgery. Previous studies have mainly focused on preoperative risk factors and intraoperative events but cerebral complications may also occur in the postoperative period. Cognitive impairment is common after cardiac surgery but the consequences of this complication for activities of daily life are less known. Safe driving involves a complex set of skills requiring preserved cognitive function. A substantial number of patients with heart disease are active drivers. The impact of postoperative cognitive dysfunction on driving performance, however, has not previously been investigated in this large patient group.

    In this thesis pre-, intra- and postoperative risk factors for focal cerebral complications were determined and the onset time of cerebral symptoms were evaluated in two cohorts of cardiac surgical patients, comprising 2480 and 3282 patients respectively. Data analysed were drafted from a clinical register and the surgical database of Linköping University Hospital Heart Center. Cerebral complication was delayed, i.e occurred after a free interval, in about one third of patients suggesting causes other than intraoperative events. Different risk factors were found for early and delayed cerebral complications suggesting different mechanisms of cerebral injury. Advanced age, preoperative hypertension, aortic surgery, prolonged cardiopulmonary bypass (CPB) time, intraoperative hypotension after completion of CPB, and arrhytlunia in the early postoperative period increased the risk for early cerebral complication. Female gender, diabetes, previous cerebrovascular disease, combined coronary artery bypass grafting (CABG) and valve surgery and arrhythmia on the thoracic ward increased the risk for delayed cerebral complication. Cognitive function and driving performance were evaluated in 27 patients before and 4-6 weeks after CABG. The patients underwent neuropsychological testing, an on-road driving test and a test in an advanced driving simulator. Twenty patients scheduled for percutaneous coronary intervention (PCI) served as controls. Complete data were obtained in 23 and 19 patients respectively. Furthermore cognitive function and driving performance in on-road driving of the 44 patients with complete tests before intervention were compared with controls of similar age without heart symptoms. Cognitive function and driving performance were already impaired in patients with coronary artery disease before intervention when compared with controls. After surgery 48% of the patients showed cognjtive decline compared to 10% after PCI. These patients also scored less in the on-road driving test to a greater extent than did patients without postoperative cognitive decline.

    List of papers
    1. Cerebral complications after coronary artery bypass and heart valve surgery: Risk factors and onset of symptoms
    Open this publication in new window or tab >>Cerebral complications after coronary artery bypass and heart valve surgery: Risk factors and onset of symptoms
    1998 (English)In: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 12, no 3, p. 270-273Article in journal (Refereed) Published
    Abstract [en]

    Objectives: Cerebral complications continue to be a major cause of morbidity after cardiac surgery. Earlier studies have mainly focused on intraoperative events, but symptoms may also occur later in the postoperative period. The purpose of this study was to determine the incidence and risk factors of focal neurologic complications and timing of cerebral symptoms.

    Design: A retrospective study.

    Setting: Linköping University Hospital.

    Participants: Two thousand four hundred eighty patients who underwent cardiac surgery from 1992 to 1995.

    Interventions: Standard cardiopulmonary bypass (CPB) technique was used in all patients. Anticoagulant treatment included heparin and patients with coronary artery surgery were also administered acetylsalicylic acid and valve-surgery patients received warfarin or dicumarol.

    Measurements and Main Results: Seventy-five patients (3%) had focal neurologic deficits and/or confusion postoperatively. In 32 patients (43%), the onset was not intraoperative but occurred later in the postoperative period. The lowest incidence of cerebral complications was found in patients who underwent single-valve replacement (1.2%) and the highest incidence was found in patients who underwent combined procedures (valve and coronary artery surgery; 7.6%). Patients greater than 70 years of age had a complication rate of 4.1% compared with 2.5% in patients aged 70 years and less (p < 0.05). The incidence of diabetes mellitus was 11.4% in the entire series, but was more common (18.7%; p < 0.05) in patients with cerebral symptoms. Also, 5.9% of all patients had a history of cerebrovascular disease compared with 14.7% (p < 0.01) of patients with cerebral complications.

    Conclusion: Cerebral complications may be delayed after cardiac surgery, suggesting causes of cerebral damage other than intraoperative events. Valve-surgery patients had the lowest incidence and patients with combined procedures had the highest incidence of cerebral complications. Advanced age, diabetes mellitus, and preexisting cerebrovascular disease increased the risk.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81345 (URN)10.1016/S1053-0770(98)90004-0 (DOI)
    Available from: 2012-09-12 Created: 2012-09-12 Last updated: 2017-12-07Bibliographically approved
    2. Risk factor analysis of early and delayed cerebral complications after cardiac surgery
    Open this publication in new window or tab >>Risk factor analysis of early and delayed cerebral complications after cardiac surgery
    2002 (English)In: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 16, no 3, p. 278-285Article in journal (Refereed) Published
    Abstract [en]

    Objective: To report the incidence, severity, and possible risk factors for early and delayed cerebral complications.

    Design: Retrospective study.

    Setting: Linköping University Hospital, Sweden.

    Participants: Consecutive patients who underwent cardiac surgery in the period July 1996 through June 2000 (n = 3,282).

    Interventions: A standard cardiopulmonary bypass (CPB) technique was used for most patients. Postoperative anticoagulant treatment included heparin or anti-Xa dalteparin. Patients undergoing coronary artery bypass graft surgery received acetylsalicylic acid, and patients undergoing valve surgery received warfarin.

    Measurements and Main Results: Cerebral complications occurred in 107 patients (3.3%). Of these, 60 (1.8%) were early, and 33 (1.0%) were delayed, and in 14 (0.4%) patients the onset was unknown. There were 37 variables in univariate analysis (p < 0.15) and 14 variables in multivariate analysis (p < 0.05) associated with cerebral complications. Predictors of early cerebral complications were older age, preoperative hypertension, aortic aneurysm surgery, prolonged CPB time, hypotension at CPB completion and soon after CPB, and postoperative arrhythmia and supraventricular tachyarrhythmia. Predictors of delayed cerebral complications were female gender, diabetes, previous cerebrovascular disease, combined valve surgery and coronary artery bypass graft surgery, postoperative supraventricular tachyarrhythmia, and prolonged ventilator support. Early cerebral complications seem to be more serious, with more permanent deficits and a higher overall mortality (35.0% v 18.2%).

    Conclusion: Most cerebral complications had an early onset. The results of this study suggest that aggressive antiarrhythmic treatment and blood pressure control may imfurther prove the cerebral outcome after cardiac surgery.

    Place, publisher, year, edition, pages
    Elsevier, 2002
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-29550 (URN)10.1053/jcan.2002.124133 (DOI)14921 (Local ID)14921 (Archive number)14921 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2018-05-22Bibliographically approved
    3. Patients with Coronary Artery Disease Are Active Car Drivers Both Before and Soon After Heart Surgery
    Open this publication in new window or tab >>Patients with Coronary Artery Disease Are Active Car Drivers Both Before and Soon After Heart Surgery
    2002 (English)In: Traffic Injury Prevention, ISSN 1538-9588, E-ISSN 1538-957X, Vol. 3, no 3, p. 205-208Article in journal (Refereed) Published
    Abstract [en]

    Cognitive ability is essential for the fitness to drive. Impaired cognitive functions are common after cardiac surgery. Little is known about driving habits and influence of postoperative cognitive decline on driving performance in these patients. The aim of this study was to investigate the extent of driving activity of patients before and after cardiac surgery. Ninety-seven cardiac surgical patients were interviewed about their driving habits before and 12 weeks after surgery. The mean age was 66. Before the operation, 78% were active car drivers. They drove several times a week including longer than 100 km distances. After the operation, 64% continued to drive and most of them (69%) had commenced driving within 6 weeks. The majority (79%) reported unchanged driving habits, while 13 patients (21%) had reduced their driving activity due to the cognitive symptoms they experienced. Patients with coronary artery disease are active car drivers both before and after heart surgery. Further evaluation of the ability of these patients to drive is required if we are to give advice and apply restrictions in the interest of traffic safety.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26733 (URN)10.1080/15389580213649 (DOI)11328 (Local ID)11328 (Archive number)11328 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. Neurocognitive impairment and driving performance after coronary artery bypass surgery
    Open this publication in new window or tab >>Neurocognitive impairment and driving performance after coronary artery bypass surgery
    Show others...
    2003 (English)In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 23, no 3, p. 334-340Article in journal (Refereed) Published
    Abstract [en]

    Objective: Neurocognitive impairment is common after cardiac surgery but few studies have examined the relationship between postoperative neuropsychological test performance and everyday behavior. The influence of postoperative cognitive impairment on car driving has previously not been investigated. The purpose of this study was to evaluate neurocognitive function and driving performance after coronary artery bypass grafting (CABG).

    Methods: Twenty-seven patients who underwent coronary artery bypass grafting with standard cardiopulmonary bypass technique and 20 patients scheduled for percutaneous coronary intervention (PCI) under local anesthesia (control group) were enrolled in this prospective study conducted from April 1999 to September 2000. Complete data were obtained in 23 and 19 patients, respectively. The patients underwent neuropsychological examination with a test battery including 12 tests, a standardized on-road driving test and a test in an advanced driving simulator before and 4–6 weeks after intervention.

    Results: More patients in the coronary artery bypass grafting group (n=11, 48%) than in the percutaneous coronary intervention group (n=2, 10%) showed a cognitive decline after intervention (P=0.01). In the on-road driving test, patients who underwent coronary artery bypass grafting deteriorated after surgery in the cognitive demanding parts like traffic behavior (P=0.01) and attention (P=0.04). Patients who underwent percutaneous intervention deteriorated in maneuvering of the vehicle (P=0.04). No deterioration was detected in the simulator in any of the groups after intervention. Patients with a cognitive decline after intervention also tended to drop in the on-road driving scores to a larger extent than did patients without a cognitive decline.

    Conclusion: This study indicates that cognitive functions important for safe driving may be influenced after cardiac surgery.

    Keywords
    Cardiac surgery, Cerebral complications, Cognitive decline, Driving performance
    National Category
    Social Sciences
    Identifiers
    urn:nbn:se:liu:diva-26290 (URN)10.1016/s1010-7940(02)00807-2 (DOI)10806 (Local ID)10806 (Archive number)10806 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    5. Driving performance of patients with coronary artery disease
    Open this publication in new window or tab >>Driving performance of patients with coronary artery disease
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Objectives To compare patients with coronary artery disease and healthy controls with respect to cognitive function and driving performance.

    Design and setting A controlled study conducted between April 1999 and January 2001.

    Subjects Forty-four patients with stable coronary artery disease scheduled for cardiac intervention with coronary artery bypass surgery or percutaneous coronary intervention. Forty volunteers of similar age without symptoms of coronary artery disease served as controls.

    Main outcome measures On-road driving scores in five specific test areas with a rating scale from 1 to 5. Neuropsychological test scores, including 12 tests.

    Results Compared with controls, patients with coronary artery disease had lower scores in all areas of the on-road driving test (p<0.05) and in the neuropsychological tests assessing psychomotor speed, visual and verbal memory, focused attention and simultaneous capacity (p<0.05). The difference between the groups in the on-road driving test appeared to be more pronounced among those above 65 years-of-age. Both patients and controls rated their performance significantly higher than the traffic inspector (p<0.05).

    Conclusions Cognitive function and driving performance may be impaired in patients with coronary artery disease.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81348 (URN)
    Available from: 2012-09-12 Created: 2012-09-12 Last updated: 2012-09-12Bibliographically approved
  • 14.
    Ahlgren, Ewa
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiothoracic Anaesthesia and Intensive care. Linköping University, Department of Medicine and Care, Thoracic Surgery. Linköping University, Faculty of Health Sciences.
    Arén, Claes
    Cerebral complications after coronary artery bypass and heart valve surgery: Risk factors and onset of symptoms1998In: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 12, no 3, p. 270-273Article in journal (Refereed)
    Abstract [en]

    Objectives: Cerebral complications continue to be a major cause of morbidity after cardiac surgery. Earlier studies have mainly focused on intraoperative events, but symptoms may also occur later in the postoperative period. The purpose of this study was to determine the incidence and risk factors of focal neurologic complications and timing of cerebral symptoms.

    Design: A retrospective study.

    Setting: Linköping University Hospital.

    Participants: Two thousand four hundred eighty patients who underwent cardiac surgery from 1992 to 1995.

    Interventions: Standard cardiopulmonary bypass (CPB) technique was used in all patients. Anticoagulant treatment included heparin and patients with coronary artery surgery were also administered acetylsalicylic acid and valve-surgery patients received warfarin or dicumarol.

    Measurements and Main Results: Seventy-five patients (3%) had focal neurologic deficits and/or confusion postoperatively. In 32 patients (43%), the onset was not intraoperative but occurred later in the postoperative period. The lowest incidence of cerebral complications was found in patients who underwent single-valve replacement (1.2%) and the highest incidence was found in patients who underwent combined procedures (valve and coronary artery surgery; 7.6%). Patients greater than 70 years of age had a complication rate of 4.1% compared with 2.5% in patients aged 70 years and less (p < 0.05). The incidence of diabetes mellitus was 11.4% in the entire series, but was more common (18.7%; p < 0.05) in patients with cerebral symptoms. Also, 5.9% of all patients had a history of cerebrovascular disease compared with 14.7% (p < 0.01) of patients with cerebral complications.

    Conclusion: Cerebral complications may be delayed after cardiac surgery, suggesting causes of cerebral damage other than intraoperative events. Valve-surgery patients had the lowest incidence and patients with combined procedures had the highest incidence of cerebral complications. Advanced age, diabetes mellitus, and preexisting cerebrovascular disease increased the risk.

  • 15.
    Ahlner, Johan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Druid, H
    Holmgren, P
    Genotyping avseende metabolism av läkemedel och droger - betydelse i forensiska sammanhang.1999In: Nordisk Rettsmedisin, ISSN 0809-1498, Vol. 5, p. 47-48Article in journal (Other (popular science, discussion, etc.))
  • 16.
    Ahlström, Christer
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Rask, Peter
    University Hospital, Örebro, Sweden .
    Karlsson, Jan-Erik
    County Hospital Ryhov, Jönköping, Sweden.
    Nylander, Eva
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Hult, Peter
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Assessment of Suspected Aortic Stenosis by Auto Mutual Information Analysis of Murmurs2007In: Engineering in Medicine and Biology Society, 2007. EMBS 2007, 2007, p. 1945-1948Conference paper (Refereed)
    Abstract [en]

    Mild sclerotic thickening of the aortic valve affects 25% of the population, and the condition causes aortic valve stenosis (AS) in 2% of adults above 65 years. Echocardiography is today the clinical standard for assessing AS. However, a cost effective and uncomplicated technique that can be used for decision support in the primary health care would be of great value. In this study, recorded phonocardiographic signals were analyzed using the first local minimum of the auto mutual information (AMI) function. The AMI method measures the complexity in the sound signal, which is related to the amount of turbulence in the blood flow and thus to the severity of the stenosis. Two previously developed phonocardiographic methods for assessing AS severity were used for comparison, the murmur energy ratio and the sound spectral averaging technique. Twenty-nine patients with suspected AS were examined with Doppler echocardiography. The aortic jet velocity was used as a reference of AS severity, and it was found to correlate with the AMI method, the murmur energy ratio and the sound spectral averaging technique with the correlation coefficient R = 0.82, R = 0.73 and R = 0.76, respectively.

  • 17.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Hult, Peter
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Rask, P
    Karlsson, J-E
    Nylander, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Using the intelligent stethoscope for extraction of features for systolic heart murmur classification2006In: World Congress on Medical Physics and Biomedical Engineering WC2006,2006, 2006Conference paper (Other academic)
  • 18.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Hult, Peter
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Schmekel, Birgitta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Automatisk detektering av ronki med icke-linjära metoder2004In: Svenska Läkaresällskapets riksstämma,2004, 2004, p. 66-66Conference paper (Other academic)
  • 19.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Hult, Peter
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Schmekel, Birgitta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Wheeze detection with nonlinear statespace embedding2004In: International Lung Sound Association,2004, 2004, p. 38-39Conference paper (Other academic)
  • 20.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    A respiration monitor based on electrocardiographic and photoplethysmographic sensor fusion2004In: IEEE Engineering in Medical and Biological Society,2004, Piscataway, N.J. USA: IEEEEMBS , 2004, p. 2311-Conference paper (Refereed)
  • 21.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Monitorering av andning and blodtrycksförändringar baserat på EKG och hjärtljud2007In: Medicinteknik dagarna,2007, 2007Conference paper (Other academic)
  • 22.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Uhlin, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Noninvasive investigation of blood pressure changes using the pulse wave transit time: A novel approach in the monitoring of hemodialysis patients2005In: Journal of Artificial Organs, ISSN 1434-7229, E-ISSN 1619-0904, Vol. 8, no 3, p. 192-197Article in journal (Refereed)
    Abstract [en]

    Severe blood pressure changes are well known in hemodialysis. Detection and prediction of these are important for the well-being of the patient and for optimizing treatment. New noninvasive methods for this purpose are required. The pulse wave transit time technique is an indirect estimation of blood pressure, and our intention is to investigate whether this technique is applicable for hemodialysis treatment. A measurement setup utilizing lower body negative pressure and isometric contraction was used to simulate dialysis-related blood pressure changes in normal test subjects. Systolic blood pressure levels were compared to different pulse wave transit times, including and excluding the cardiac preejection period. Based on the results of these investigations, a pulse wave transit time technique adapted for dialysis treatment was developed and tried out on patients. To determine systolic blood pressure in the normal group, the total pulse wave transit time was found most suitable (including the cardiac preejection period). Correlation coefficients were r = 0.80 ± 0.06 (mean ± SD) overall and r = 0.81 ± 0.16 and r = 0.09 ± 0.62 for the hypotension and hypertension phases, respectively. When applying the adapted technique in dialysis patients, large blood pressure variations could easily be detected when present. Pulse wave transit time is correlated to systolic blood pressure within the acceptable range for a trend-indicating system. The method's applicability for dialysis treatment requires further studies. The results indicate that large sudden pressure drops, like those seen in sudden hypovolemia, can be detected. © The Japanese Society for Artificial Organs 2005.

  • 23.
    Ahlström, Gerd
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nursing Science.
    Carlsson, C
    Att visa upp sin värld: Hur personer med stora varaktiga funktionshinder uppfattar sin livssituation relaterat till de etiska principerna i LSS2002Report (Other academic)
  • 24.
    Ahlström, Gerd
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nursing Science.
    Wennberg, S
    Coping with illness-related problems in persons with progressive muscular diseases: the Swedish version of the Ways of Coping Questionnaire2002In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 16, p. 368-375Article in journal (Refereed)
  • 25.
    Ahn, Henrik Casimir
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Mitral valve surgery - current results and future development to catheter based approaches2006In: International Society of Extracorporeal Circulation - Cardiac Surgery beyond 2006,2006, 2006Conference paper (Other academic)
  • 26.
    Ahn, Henrik Casimir
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    The Impella temporary assist device, the Swedish experience2006In: International Society of Extracorporeal Circulation - Cardiac Surgery beyond 2006,2006, 2006Conference paper (Other academic)
  • 27.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Jodal, M.
    Lindhagen, J
    Lundgren, O.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Bestämning av tunntarmsblodflödet med laser Doppler teknik1984In: Läkarsällskapets Riksstämma,1984, 1984Conference paper (Other academic)
  • 28.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Johansson, K.
    Lindhagen, J.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Förändringar av blodflödet i ventrikeln i samband med mätt med laser Dopplerteknik1984In: Läkarsällskapets Riksstämma,1984, 1984Conference paper (Other academic)
  • 29.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Johansson, K.
    Lindhagen, J.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Laser Doppler flowmetry in the assessment of gastric blood flow1984In: man. Scand J of Gastroenterology,1984, 1984, p. 98:33-98:33Conference paper (Other academic)
  • 30.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Lindhagen, J.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Jodal, M.
    Lundgren, O.
    Evaluation of Laser Doppler Flowmetry in the assessment of blood flow in the small intestine1984In: Third World Congress of Microcirculation,1984, 1984Conference paper (Other academic)
  • 31.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Lindhagen, J
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Jodal, M
    Lundgren, O
    Evaluation of Laser Doppler Flowmetry in the assessment of intestinal blood flow1985In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 4, no 88, p. 951-957Article in journal (Refereed)
    Abstract [en]

      

  • 32.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Lönn, Urban
    IMV/Thoraxkirurgi/Hjärtcentrum LiU/HU.
    Peterzén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Alternatives to circulatory support during coronary artery surgery1999In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 16 suppl 2, p. 143-150Article in journal (Refereed)
  • 33.
    Aifa, Sami
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Aydin, J
    Nordvall, G
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Svensson, Samuel
    Hermanson, O
    A basic peptide within the juxtamembrane region is required for EGF receptor dimerization2005In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 302, no 1, p. 108-114Article in journal (Refereed)
    Abstract [en]

    The epidermal growth factor receptor (EGFR) is fundamental for normal cell growth and organ development, but has also been implicated in various pathologies, notably tumors of epithelial origin. We have previously shown that the initial 13 amino acids (P13) within the intracellular juxtamembrane region (R645-R657) are involved in the interaction with calmodulin, thus indicating an important role for this region in EGFR function. Here we show that P13 is required for proper dimerization of the receptor. We expressed either the intracellular domain of EGFR (TKJM) or the intracellular domain lacking P13 (ΔTKJM) in COS-7 cells that express endogenous EGFR. Only TKJM was immunoprecipitated with an antibody directed against the extracellular part of EGFR, and only TKJM was tyrosine phosphorylated by endogenous EGFR. Using SK-N-MC cells, which do not express endogenous EGFR, that were stably transfected with either wild-type EGFR or recombinant full-length EGFR lacking P13 demonstrated that P13 is required for appropriate receptor dimerization. Furthermore, mutant EGFR lacking P13 failed to be autophosphorylated. P13 is rich in basic amino acids and in silico modeling of the EGFR in conjunction with our results suggests a novel role for the juxtamembrane domain (JM) of EGFR in mediating intracellular dimerization and thus receptor kinase activation and function. © 2004 Elsevier Inc. All rights reserved.

  • 34. Aifa, Sami
    et al.
    Johansen, Knut
    Nilsson, Ulrica K
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Lundström, Ingemar
    Svensson, Samuel
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Interactions between the juxtamembrane domain of the EGFR and calmodulin measured by surface plasmon resonance2002In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 14, no 12, p. 1005-1013Article in journal (Refereed)
    Abstract [en]

    One early response to epidermal growth factor receptor (EGFR) activation is an increase in intracellular calcium. We have used surface plasmon resonance (SPR) to study real-time interactions between the intracellular juxtamembrane (JM) region of EGFR and calmodulin. The EGFR-JM (Met644-Phe688) was expressed as a GST fusion protein and immobilised on a sensor chip surface. Calmodulin specifically interacts with EGFR-JM in a calcium-dependent manner with a high on and high off rate. Chemical modification of EGFR-JM by using arginine-selective phenylglyoxal or deletion of the basic segment Arg645-Arg657 inhibits the interaction. Phosphorylation of EGFR-JM by protein kinase C (PKC) or glutamate substitution of Thr654 inhibits the interaction, suggesting that PKC phosphorylation electrostatically interferes with calmodulin binding to basic arginine residues. Calmodulin binding was also inhibited by suramin. Our results suggest that EGFR-JM is essential for epidermal growth factor (EGF)-mediated calcium-calmodulin signalling and for signal integration between other signalling pathways.

  • 35.
    Aifa, Sami
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Miled, N
    Frikha, F
    Aniba, MR
    Svensson, Samuel
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Rebai, A
    Electrostatic interactions of peptides flanking the tyrosine kinase domain in the epidermal growth factor receptor provides a model for intracellular dimerization and autophosphorylation2006In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 62, no 4, p. 1036-1043Article in journal (Refereed)
    Abstract [en]

    The mechanism by which ligand-activated EGFR induces autophosphorylation via dimerization is not fully understood. Structural studies have revealed an extracellular loop mediated receptor dimerization. We have previously presented experimental data showing the involvement of a positive 13 amino acid peptide (R645-R657, P13+) from the intracellular juxtamembrane domain (JM) of EGFR important for intracellular dimerization and autophosphorylation. A model was presented that suggest that P13+ interacts with a negative peptide (D979-E991, P13-) positioned distal to the tyrosine kinase domain in the opposite EGFR monomer. The present work shows additional data strengthening this model. In fact, by analyzing protein sequences of 21 annotated ErbB proteins from 9 vertebrate genomes, we reveal the high conservation of peptides P13+ and P13- with regard to their sequence as well as their position relative to the tyrosine kinase (TK) domain. Moreover in silico structure modeling of these ErbB intracellular domains supports a general electrostatic P13+/P13- interaction, implying that the C-terminal of one receptor monomer is facing the TK domain of the other monomer in the receptor dimer and vice versa. This model provides new insights into the molecular mechanism of ErbB receptor activation and suggests a new strategy to pharmacologically interfering with ErbB receptor activity. © 2005 Wiley-Liss, Inc.

  • 36. Ajari, A
    et al.
    Bergqvist, D
    Elfström, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery.
    Örtenvall, P
    Troeng, T
    Hedberg, B
    Ljungström, KG
    Norgren, L
    Diabetes mellitus as a risk factor for early outcome after carotid endarterectomy - a population study.1999In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 18, p. 122-126Article in journal (Refereed)
  • 37.
    Alberth, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology.
    Kettissen, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Lisander, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Blood loss in prosthetic hip replacement is not influenced by the AB0 blood group2001In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 167, no 9, p. 652-655Article in journal (Refereed)
    Abstract [en]

    Objective: To find out if there is a correlation between AB0 type and the amount of blood lost at operation. Design: Retrospective study. Setting: One county and one university hospital, Sweden. Subjects: 540 patients who underwent primary prosthetic hip replacement under regional anaesthesia. Albumin (n = 298) or dextran (n = 242) were used as plasma substitutes. Main outcome measures: Estimated blood loss and number of units of red cell concentrates transfused. Results: The characteristics of the study groups were similar. In patients given albumin, the mean (SD) intraoperative loss with blood group 0 (n = 100) was 718 (413) ml and 2.7 (1.9) red cell units were given. Those with other blood groups (n = 198) lost 713 (469) ml and were given 2.5 (2.0) units. In patients given dextran with blood group 0 (n = 82), the intraoperative blood loss was 650 (337) ml, the postoperative loss 480 (222) ml and they received 2.1 (2.1) units. The corresponding values in the patients with other blood groups (n = 160) were 665 (351), 498 (208) and 2.5 (2.1) units. Conclusion: Blood group 0 was not associated with increased blood loss.

  • 38.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Gender and Medicine. Linköping University, Faculty of Health Sciences.
    Lundberg, Ulf
    Division of Biological Psychology, Department of Psychology, Stockholm University, Stockholm, Sweden.
    Wijma, Klaas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Psychology. Linköping University, Faculty of Health Sciences.
    Fear, pain and stress hormones during childbirth2005In: Journal of Psychosomatic Obstetrics and Gynaecology, ISSN 0167-482X, E-ISSN 1743-8942, Vol. 26, no 3, p. 153-165Article in journal (Refereed)
    Abstract [en]

    Aims. To investigate the course of fear, pain and stress hormones during labor, and the associations between fear, pain, stress hormones and duration of labor in nulliparous women with and without epidural analgesia (EDA).

    Method.  One day during gestation weeks 37–39, urinary and salivary samples were collected to measure catecholamines and cortisol. Hourly during labor, the participants answered the Delivery Fear Scale and a pain intensity scale, and urinary and salivary samples were collected to measure stress hormones.

    Results. The course of fear, pain and stress hormones differed throughout labor in women with and without EDA. Pain and cortisol increased throughout labor in women without EDA. Women who received EDA had more fear, but not more pain, before the administration of the EDA than women who did not receive EDA. Pain, fear and catecholamines decreased when women received EDA, but fear and pain increased again later in labor. Fear and pain correlated, as well as levels of fear in the different phases of labor. During phase one of labor epinephrine and duration of the phase were negatively correlated.

    Conclusion.  The course of fear, pain and concentrations of stress hormones differed, highly influenced by the administration of EDA. Fear and pain correlated more pronounced than stress hormones and fear, pain and duration of labor.

  • 39.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Gender and Medicine. Linköping University, Faculty of Health Sciences.
    Wijma, Klaas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Psychology. Linköping University, Faculty of Health Sciences.
    Fear of childbirth before, during, and after childbirth2006In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 85, no 1, p. 56-62Article in journal (Refereed)
    Abstract [en]

    Background. Only scanty research exists about the relationship between women's expectations during pregnancy and their experiences as reported during the actual process of labor and afterwards. The aims of the present study were: 1. to investigate the associations between fear of childbirth during pregnancy and postpartum and fear and pain during early active labor (phase 1: cervix dilatation 3–5 cm), and 2. to explore possible differences regarding fear of childbirth during pregnancy and postpartum between women who did or did not receive epidural analgesia during labor.

    Methods. Fear of childbirth was measured in 47 nulliparous women during gestation weeks 37–39 by means of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ version A). During early active labor we measured women's fear (Delivery Fear Scale) and their experiences of pain (a pain intensity scale). Finally, fear after childbirth (W-DEQ version B) was measured two hours, two days, and five weeks after delivery.

    Results. A positive correlation appeared between fear of childbirth during pregnancy, postpartum, and early active labor. There were no differences in fear of childbirth during late pregnancy between women who received epidural analgesia and those who did not. Postpartum fear was higher in the women who had received epidural analgesia.

    Conclusions. Pregnant women who fear childbirth are prone to report fear during the actual labor and postpartum. The administration of epidural analgesia is not a sufficient response to women's fear during the process of labor.

  • 40.
    Alehagen, Urban
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Heart failure in primary health care: special emphasis on natriuretic peptides in the elderly2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: This thesis focuses on heart failure among elderly patients in the community who usually are not included in studies on heart failure. The heart failure syndrome is an increasing problem in Western society. Severe heart failure is often easy to diagnose compared with light to moderate heart failure, which is more frequent in patients in the community,

    Doppler echocardiography is the most commonly used method to objectively verify an abnormal cardiac function, mostly the systolic function. One goal of this thesis was to evaluate both the systolic and diastolic functions. Another goal was a study of the possible utility of the B-type natriuretic peptide, BNP (brain natriuretic peptide), and the amino terminal fragment of its precursor, proBNP (N-terminal proBNP) as tools in the diagnosis of heart failure in elderly patients.

    Methods: In a primary health care setting, 510 elderly patients (age range 65-82 years) with symptoms and signs possibly associated with heart failure were examined concerning patient history, ongoing pharmacological treatment, clinical examination, chest x-ray, electrocardiogram, Doppler echo cardiography, and selected biochemical measurements of blood samples. Additionally, the natriuretic peptide BNP and the aminoterminal fragment of proBNP were analyzed for a possible influence of gender, age, impaired cardiac function assessed using Doppler echocardiography, other diseases, and phannacological treatment. We followed our study population for six years, carefully registering mortality with death certificates. This information was used in analyzing the risk of cardiovascular death based on Cox proportional hazard regression. We present a model for estimating the risk of cardiovascular death in the individual patient.

    Results: Almost half of our study population [mean age 73 (SD 6) years] with symptoms of possible heart failure had signs of impaired cardiac function on Doppler echocardiography. Half of these individuals had isolated impairment of the diastolic function. Almost two thirds of the elderly patients who had an ejection fraction of less than 40% did not receive treatment with ACE inhibitors, one of the cornerstones in the treatment of heart failure.

    BNP and N-terminal proBNP were equally effective in detecting impaired cardiac function. As a response to increased filling pressure they probably provide earlier information on the haemodynamic situation than Doppler echocardiography does.

    In these elderly patients, functional class (NYHA class III: 7 times increased risk), in vivo examination by Doppler echo cardiography (EF<30%: 8 times increased risk) and the in vitro measurement of plasma BNP (>27.8 pmol/L: 11 times increased risk) and N-terminal proBNP (>109 pmol/L: 7 times increased risk) could be used as prognostic determinants in assessing the risk of cardiovascular death.

    Conclusion: The results indicate that a focused patient history and clinical examination provides important information that is often sufficient for the prognostic evaluation of a patient with heart failure symptoms. Additional information may be obtained with Doppler echo cardiographic examination and measurement of plasma BNP or N-terminal proBNP. The relationship between BNPIN-terminal proBNP concentration and risk of cardiovascular death may be analysed to define decision limits for the concentrations of these peptides as regards further diagnostic procedures and/or phannaceutical treatment.

    List of papers
    1. Heart failure in the elderly: characteristics of a Swedish primary health care population
    Open this publication in new window or tab >>Heart failure in the elderly: characteristics of a Swedish primary health care population
    2002 (English)In: Heart Drug, ISSN 1422-9528, E-ISSN 1424-0556, Vol. 2, no 5, p. 211-220Article in journal (Refereed) Published
    Abstract [en]

    Background: Heart failure (HF) is a challenge to diagnose and treat according to guidelines. Few studies have been performed in elderly subjects with symptoms that might be associated with HF in primary health care.

    Objective: To study elderly patients presenting with symptoms possibly associated with HF, with respect to systolic and diastolic function, B-type natriuretic peptide (BNP) levels and treatment.

    Methods: A cardiologist examined 415 elderly (65–82 years) patients with symptoms of dyspnoea, fatigue and/or peripheral oedema. All patients underwent echocardiography and plasma BNP determination. Systolic function was determined semiquantitatively, and ejection fraction (EF) <40% was considered to be reduced. Abnormal diastolic function was defined as a reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio; age adjusted) or an abnormal pattern of pulmonary venous flow.

    Results: Forty-eight percent of the patients showed abnormal systolic (26%) or diastolic function (22%). A majority of the patients with diastolic HF had relaxation abnormalities and neither pseudonormal nor restrictive filling patterns. Increased levels of BNP were found in the group with impaired systolic function. More than half of those with EF <40% were not receiving angiotensin-converting enzyme inhibitions at all, or were on a suboptimal dose, whereas others were on treatment for an HF diagnosis despite normal cardiac function.

    Conclusion: Diagnostic tools that are more objective than clinical examination are needed for the diagnosis of HF.

    Keywords
    Elderly patients, Heart failure, Primary health care
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-46849 (URN)10.1159/000067723 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    2. Utility of the amino-terminal fragment of pro-brain natriuretic peptide in plasma for the evaluation of cardiac dysfunction in elderly patients in primary health care
    Open this publication in new window or tab >>Utility of the amino-terminal fragment of pro-brain natriuretic peptide in plasma for the evaluation of cardiac dysfunction in elderly patients in primary health care
    2003 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 49, no 8, p. 1337-1346Article in journal (Refereed) Published
    Abstract [en]

    Background: The aims of this study were to measure the N-terminal fragment of pro-brain natriuretic peptide (proBNP) in plasma in medical conditions commonly found in primary care and to evaluate the utility of these measurements in identifying impaired cardiac function in elderly patients with symptoms associated with heart failure.

    Methods: We studied 415 patients (221 men and 194 women; mean age, 72 years) who had contacted a primary healthcare center for dyspnea, fatigue, and/or peripheral edema. One cardiologist evaluated the patients in terms of history, physical examination, functional capacity, electrocardiography, and suspicion of heart failure. Plasma N-terminal proBNP was measured by an in-house RIA. An ejection fraction ≤40% by Doppler echocardiography was regarded as reduced cardiac function. Abnormal diastolic function was defined as an abnormal mitral inflow defined as reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio), or as abnormal pulmonary venous flow pattern.

    Results: Patients with impaired functional capacity, impaired systolic function, and/or impaired renal function had significantly increased N-terminal proBNP concentrations. By multiple regression analysis, N-terminal proBNP concentrations were also influenced by ischemic heart disease, cardiac enlargement, and certain medications but not by increased creatinine. No gender differences were observed. Patients with isolated diastolic dysfunction attributable to relaxation abnormali-ties had lower concentrations than those with normal cardiac function, whereas those with pseudonormal E/A ratios or restrictive filling patterns had higher concentrations.

    Conclusions: Plasma N-terminal proBNP concentrations increase as a result of impaired systolic function, age, impaired renal function, cardiac ischemia and enlargement, and certain medications. Values are high in diastolic dysfunction with pseudonormal patterns, but not in patients with relaxation abnormalities. An increase in plasma N-terminal proBNP might be an earlier sign of abnormal cardiac function than abnormalities identified by currently used echocardiographic measurements.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26758 (URN)10.1373/49.8.1337 (DOI)11356 (Local ID)11356 (Archive number)11356 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. The risk of cardiovascular death in elderly patients with possible heart failure: results from a 6-year follow-up of a Swedish primary care population
    Open this publication in new window or tab >>The risk of cardiovascular death in elderly patients with possible heart failure: results from a 6-year follow-up of a Swedish primary care population
    2005 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 100, no 1, p. 17-27Article in journal (Refereed) Published
    Abstract [en]

    Little is known about the prognosis and clinical variables influencing the prognosis among elderly patients in primary health care with mild to moderate heart failure.

    Aim: To evaluate the risk of cardiovascular mortality in elderly patients with symptoms of heart failure with respect to systolic and diastolic function, and functional impairment. To evaluate prognostic determinants and to risk-stratify the patients.

    Methods: A cardiologist examined 510 patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed New York Heart Association (NYHA) functional class. Examination by Doppler echocardiography was done in 454 patients, 56 patients being excluded because of, e.g., atrial fibrillation. Abnormal systolic function was defined as ejection fraction <40%. The diastolic function was evaluated using the mitral inflow and pulmonary venous flow variables. Different clinical and echocardiographic variables were analysed using a Cox regression analysis to identify those most influencing the risk of cardiovascular mortality.

    Conclusion: Abnormal systolic and/or diastolic function was found in 219 patients (48% of the 454 patients who could be echocardiographically completely investigated). The follow-up period was 6 years. Total mortality was 20%, and cardiovascular mortality was 14% (70% of total mortality). Cardiovascular mortality was high in patients with severely impaired functional capacity and ejection fraction <40% at the start of the study. Risk variables identified were male gender, diabetes mellitus, impaired functional capacity and abnormal cardiac function by echocardiography. A prognostic score model using simple clinical variables (gender, NYHA class, cardiac function) was developed to assess the risk of cardiovascular death in order to identify patients with high, moderate or low risk. In a ROC curve analysis, the AUC for clinical variables was only 0.75, whereas the AUC for clinical variables and echocardiography was 0.78, indicating that the additional prognostic information obtained by Doppler echocardiography was rather small.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-33737 (URN)10.1016/j.ijcard.2004.03.031 (DOI)19779 (Local ID)19779 (Archive number)19779 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
    4. Results from a 6-year follow-up of a Swedish population in primary care regarding b-type natriuretic peptide (bnp) and the aminoterminal fragment of proBNP (n-terminal proBNP) and risk for cardiovascular death in elderly patients with possible heart failure.
    Open this publication in new window or tab >>Results from a 6-year follow-up of a Swedish population in primary care regarding b-type natriuretic peptide (bnp) and the aminoterminal fragment of proBNP (n-terminal proBNP) and risk for cardiovascular death in elderly patients with possible heart failure.
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Heart failure is common in the elderly population and carries a serious prognosis. Identification of risk factors for cardiovascular mortality among primary care patients is important.

    Aim

    To evaluate EDTA-plasma brain natriuretic peptide (BNP) and the aminoterminal fragment of proBNP (N-terminal proBNP) as prognostic markers in elderly with symptoms of mild to moderate heart failure.

    Methods

    From 474 patients attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema blood was sampled in plastic tubes containing EDTA in order to measure BNP by non-extraction immunoradiometric assay and of N-terminal proBNP by non-extraction radioimmunoassay. Patients were evaluated with respect to history and clinical- and laboratory examinations with particular reference to cardiac structure and function. Follow-up time was 6 years. A Cox regression analysis was performed to identify the weight of risk variables.

    Conclusion

    During the follow-up period of 6 years the total mortality was 16 % (75 patients out of 474), and cardiovascular mortality was 11% (52 patients). Cardiovascular mortality increased with increased plasma concentration of BNP or N-terminal proBNP. Both pep tides were useful prognostic markers for cardiovascular mortality in patients with heart failure. In those with the highest quartile of plasma concentration of BNP and N=terminal proBNP, 9.9 times and 5.0 times increased risk for CV death were identified respectively.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84703 (URN)
    Available from: 2012-10-17 Created: 2012-10-17 Last updated: 2013-09-26Bibliographically approved
  • 41.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure2004In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 92, no 6, p. 1250-1258Article in journal (Refereed)
    Abstract [en]

    D-dimer, a marker of fibrin turnover, exhibits many interesting properties as a biological marker of thrombosis. Some of the properties of D-dimer might also be used to provide additional information about patients with heart failure. In this study, we evaluate the prognostic information acquired from D-dimer concerning increased risk of cardiovascular mortality in an elderly population with symptoms associated with heart failure. A cardiologist examined 458 elderly patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed NYHA functional class and cardiac function. Abnormal systolic function was defined as EF <40% on Doppler echocardiography. Abnormal diastolic function was defined as reduced E/A ratio and/or an abnormal pattern of pulmonary venous flow. Blood samples were drawn, and BNP and D-dimer were analysed. D-dimer was analysed using an automated micro-latex assay. A statistical analysis was performed to identify the prognostic value of increased plasma concentration of D-dimer. Results showed that during a median follow-up period of 5.5 years, 68 (14%) patients died of cardiovascular disease. No gender difference was noted. A plasma concentration of D-dimer >0.25mg/L increased the risk almost 4-fold. In conclusion, D-dimer is an independent risk factor for cardiovascular mortality that may be used to risk-stratify patients with heart failure. © 2004 Schattauer GmbH, Stuttgart.

  • 42.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Goetze, JP
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Reference intervals and decision limits for B-type natriuretic peptide (BNP) and its precursor (Nt-proBNP) in the elderly2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 382, no 1-2Article in journal (Refereed)
    Abstract [en]

    Background: Elderly patients have the highest prevalence of heart failure (HF). The aims of the study were to establish a reference interval for B-type natriuretic peptide (BNP) and (Nt-proBNP) in elderly people, and to identify clinically relevant decision limits based on long-term outcome. Methods: Plasma concentrations of BNP and Nt-proBNP were measured from two elderly populations: 218 healthy subjects (mean age 73 years, population I), and 474 patients (mean age 73 years, population II) with symptoms associated with HF. Study population II was followed for 6 years with registration of all cardiovascular mortality. Results: An association between both BNP and Nt-proBNP concentrations and age was found. The upper limit for the reference intervals in the healthy elderly (population I) was: BNP ≤ 28 pmol/L (≤ 97 ng/L), and Nt-proBNP ≤ 64 pmol/L (≤ 540 ng/L). Based on cardiovascular mortality, decision limits for BNP (∼ 50 pmol/L, ∼ 170 ng/L) and Nt-proBNP (∼ 200 pmol/L, ∼ 1700 ng/L) (population II) were determined. Conclusions: Besides establishing reference intervals for BNP and Nt-proBNP in an elderly population, a higher clinically relevant decision limit for BNP and Nt-proBNP was identified, indicating additive prognostic information of the peptides on top of measurements by echocardiography. Therefore, both reference intervals and decision limits should be included in clinical practice. © 2007.

  • 43.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Lindstedt, G.
    Sahlgren Academy at Gothenburg University, Gothenburg, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Results from a 6-year follow-up of a Swedish population in primary care regarding b-type natriuretic peptide (bnp) and the aminoterminal fragment of proBNP (n-terminal proBNP) and risk for cardiovascular death in elderly patients with possible heart failure.Manuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Heart failure is common in the elderly population and carries a serious prognosis. Identification of risk factors for cardiovascular mortality among primary care patients is important.

    Aim

    To evaluate EDTA-plasma brain natriuretic peptide (BNP) and the aminoterminal fragment of proBNP (N-terminal proBNP) as prognostic markers in elderly with symptoms of mild to moderate heart failure.

    Methods

    From 474 patients attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema blood was sampled in plastic tubes containing EDTA in order to measure BNP by non-extraction immunoradiometric assay and of N-terminal proBNP by non-extraction radioimmunoassay. Patients were evaluated with respect to history and clinical- and laboratory examinations with particular reference to cardiac structure and function. Follow-up time was 6 years. A Cox regression analysis was performed to identify the weight of risk variables.

    Conclusion

    During the follow-up period of 6 years the total mortality was 16 % (75 patients out of 474), and cardiovascular mortality was 11% (52 patients). Cardiovascular mortality increased with increased plasma concentration of BNP or N-terminal proBNP. Both pep tides were useful prognostic markers for cardiovascular mortality in patients with heart failure. In those with the highest quartile of plasma concentration of BNP and N=terminal proBNP, 9.9 times and 5.0 times increased risk for CV death were identified respectively.

  • 44.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindstedt, G
    Göteborgs universitet.
    Levin, Lars-Åke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Risk of cardiovascular death in elderly patients with possible heart failure. B-type natriuretic peptide (BNP) and the aminoterminal fragment of ProBNP (N-terminal proBNP) as prognostic indicators in a 6-year follow-up of a primary care population2005In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 100, no 1, p. 125-133Article in journal (Refereed)
    Abstract [en]

    Heart failure is common in the elderly population and carries a serious prognosis. We evaluated EDTA-plasma B-type natriuretic peptide (brain natriuretic peptide, BNP) and the aminoterminal fragment of proBNP (N-terminal proBNP) as prognostic markers in elderly primary care patients with symptoms of heart failure. Methods: From 474 patients attending primary care for symptoms of dyspnea, fatigue and/or peripheral edema, blood was sampled in plastic tubes containing EDTA to measure BNP by non-extraction immunoradiometric assay and N-terminal proBNP by non-extraction radioimmunoassay. Patients were evaluated with respect to history and function by NYHA classification and Doppler echocardiography. Follow-up time was 6 years. Cox regression analysis was performed to identify the weight of risk variables. Conclusion: Total 6-year mortality was 20% (102 patients out of 510), and cardiovascular (CV) mortality was 14% (71 patients, 70% of total mortality). BNP and N-terminal proBNP were essentially equally useful as prognostic markers. In patients with the highest quartiles of plasma concentration of BNP and N-terminal proBNP, respectively, the risk of cardiovascular mortality was 10 and 4.8 times, respectively, higher than that in those in the lowest quartile. Peptide concentrations varied widely within all functional groups including those with normal echocardiographic findings. Plasma concentrations of BNP and N-terminal proBNP give important prognostic information concerning risk of cardiovascular mortality. Cost-effective "clinical pathways" should be outlined for patients with elevated peptide concentrations. © 2005 Elsevier Ireland Ltd. All rights reserved.

  • 45.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre. Linköping University, Faculty of Health Sciences.
    Lindstedt, G.
    Sahlgren Academy at Gothenburg University, Gothenburg, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    The risk of cardiovascular death in elderly patients with possible heart failure: results from a 6-year follow-up of a Swedish primary care population2005In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 100, no 1, p. 17-27Article in journal (Refereed)
    Abstract [en]

    Little is known about the prognosis and clinical variables influencing the prognosis among elderly patients in primary health care with mild to moderate heart failure.

    Aim: To evaluate the risk of cardiovascular mortality in elderly patients with symptoms of heart failure with respect to systolic and diastolic function, and functional impairment. To evaluate prognostic determinants and to risk-stratify the patients.

    Methods: A cardiologist examined 510 patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed New York Heart Association (NYHA) functional class. Examination by Doppler echocardiography was done in 454 patients, 56 patients being excluded because of, e.g., atrial fibrillation. Abnormal systolic function was defined as ejection fraction <40%. The diastolic function was evaluated using the mitral inflow and pulmonary venous flow variables. Different clinical and echocardiographic variables were analysed using a Cox regression analysis to identify those most influencing the risk of cardiovascular mortality.

    Conclusion: Abnormal systolic and/or diastolic function was found in 219 patients (48% of the 454 patients who could be echocardiographically completely investigated). The follow-up period was 6 years. Total mortality was 20%, and cardiovascular mortality was 14% (70% of total mortality). Cardiovascular mortality was high in patients with severely impaired functional capacity and ejection fraction <40% at the start of the study. Risk variables identified were male gender, diabetes mellitus, impaired functional capacity and abnormal cardiac function by echocardiography. A prognostic score model using simple clinical variables (gender, NYHA class, cardiac function) was developed to assess the risk of cardiovascular death in order to identify patients with high, moderate or low risk. In a ROC curve analysis, the AUC for clinical variables was only 0.75, whereas the AUC for clinical variables and echocardiography was 0.78, indicating that the additional prognostic information obtained by Doppler echocardiography was rather small.

  • 46.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Lindstedt, Göran
    Sahlgren Academy at Gothenburg University, Gothenburg, Sweden.
    Eriksson, Henry
    Department of Medicine, Sahlgrenska University Hospital-Östra, Gothenburg, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Utility of the amino-terminal fragment of pro-brain natriuretic peptide in plasma for the evaluation of cardiac dysfunction in elderly patients in primary health care2003In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 49, no 8, p. 1337-1346Article in journal (Refereed)
    Abstract [en]

    Background: The aims of this study were to measure the N-terminal fragment of pro-brain natriuretic peptide (proBNP) in plasma in medical conditions commonly found in primary care and to evaluate the utility of these measurements in identifying impaired cardiac function in elderly patients with symptoms associated with heart failure.

    Methods: We studied 415 patients (221 men and 194 women; mean age, 72 years) who had contacted a primary healthcare center for dyspnea, fatigue, and/or peripheral edema. One cardiologist evaluated the patients in terms of history, physical examination, functional capacity, electrocardiography, and suspicion of heart failure. Plasma N-terminal proBNP was measured by an in-house RIA. An ejection fraction ≤40% by Doppler echocardiography was regarded as reduced cardiac function. Abnormal diastolic function was defined as an abnormal mitral inflow defined as reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio), or as abnormal pulmonary venous flow pattern.

    Results: Patients with impaired functional capacity, impaired systolic function, and/or impaired renal function had significantly increased N-terminal proBNP concentrations. By multiple regression analysis, N-terminal proBNP concentrations were also influenced by ischemic heart disease, cardiac enlargement, and certain medications but not by increased creatinine. No gender differences were observed. Patients with isolated diastolic dysfunction attributable to relaxation abnormali-ties had lower concentrations than those with normal cardiac function, whereas those with pseudonormal E/A ratios or restrictive filling patterns had higher concentrations.

    Conclusions: Plasma N-terminal proBNP concentrations increase as a result of impaired systolic function, age, impaired renal function, cardiac ischemia and enlargement, and certain medications. Values are high in diastolic dysfunction with pseudonormal patterns, but not in patients with relaxation abnormalities. An increase in plasma N-terminal proBNP might be an earlier sign of abnormal cardiac function than abnormalities identified by currently used echocardiographic measurements.

  • 47.
    Alfredsson, Joakim
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Sederholm Lawesson, Sofia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Stenestrand, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Wallentin, Lars
    Uppsala.
    Swahn, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Gender influence tretment and outcome of patients with unstable coronary artery disease.2003In: European Heart Journal,2003, 2003, p. 72-72Conference paper (Refereed)
  • 48.
    Alfredsson, Joakim
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Sederholm Lawesson, Sofia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Stenestrand, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Wallentin, Lars
    Uppsala.
    Swahn, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Unstable coronary artery disease - a missed diagnosis.2003In: European Heart Journal,2003, 2003, p. 74-74Conference paper (Refereed)
  • 49.
    Alfredsson, Joakim
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Stenestrand, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Wallentin, L
    Swahn, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Sex-based differences in management and outcome in unstable coronary artery disease2005In: Second International Conference on Women, Heart disease and Stroke,2005, 2005Conference paper (Other academic)
  • 50.
    Alfredsson, Joakim
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Swahn, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Stenestrand, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Wallentin, L
    ST-segment depression and elevated biochemical cardiac markers are highly predictive of worse outcome in both women and men.2004In: XXVI Congress of the European Soceity of Cardiology,2004, 2004, p. 1762-1762Conference paper (Other academic)
1234567 1 - 50 of 2229
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